PMID- 1883738 TI - The effect of HeNe laser radiation on the thyroid gland of the rat. AB - Although laser irradiation is becoming common practice in medicine, there is not always a clear understanding of the possible side-effects. The present report is a light and electron microscopic study of the effects of fixed low intensity doses of soft HeNe laser on the thyroid of Wistar rats. The immediate effects are mild multifocal degenerative changes; these lesions recover in less than 3 months. Long-term lesions are identified only by electron microscopy; they consist of an increased number of peroxisomes and free or intramitochondrial crystalline structures. We discuss the laser's hypothetical functions. PMID- 1883739 TI - Experimental allergic alveolitis after exposure to different microorganisms. AB - The experiments described here examined the capacity of different microorganisms to induce allergic alveolitis. Guinea-pigs were exposed to an aerosol of pure cultures of five different organisms, four of which are common in mouldy hay, without previous injection of an adjuvant. The animals were either acutely exposed or exposed for 3 to 5 weeks, after which the numbers of different inflammatory cells in the airways were counted and histological changes in the lung parenchyma were assessed. It was seen that prolonged exposures to large numbers of spores produced a cellular infiltration in the alveolar and bronchiolar region, and gave rise to lesions resembling early granulomas. The number of lymphocytes increased in the airways. The results suggest that allergic alveolitis can be induced by inhalation of various kinds of microorganisms and that these may vary in their capacity to produce the disease. PMID- 1883740 TI - Immunocytochemical investigation of the tissue of origin of two lung cancer cell lines. AB - The constitutive cell types of the two lung cancer cell lines CaLu1 and CaLu3 have been investigated by immunocytochemical staining with markers for cytokeratins, vimentin, carcinoembryonic antigen and the epithelial cell epitope recognized by the monoclonal antibody Ber-EP4. The cells of both lines reacted with vimentin, with CAM 5.2, which is a marker for cytokeratins 8, 18 and 19, and with a specific marker for cytokeratin 19. CaLu3 cultures showed patchy staining, and CaLu1 none, when treated with a monoclonal antibody reactive with cytokeratins 13, 14 and 17. CaLu3 cells all reacted strongly with Ber-EP4 and the antibody to carcinoembryonic antigen, whereas CaLu1 gave a negative reaction with both these reagents. These results indicate that the CaLu3 line has retained antigens characteristic of some bronchial adenocarcinomata, and that the CaLu1 line was derived from a mesothelioma rather than a pleural metastasis of a squamous carcinoma. PMID- 1883741 TI - Selective killing of Paneth cells by intravenous administration of dithizone in rats. AB - Paneth cells are zinc-containing cells widely distributed in Lieberkuhn's crypts of intestine in a variety of species. We found that rapid selective killing of Paneth cells took place after the intravenous (i.v.) injection of diphenylthiocarbazone (dithizone), a chelator forming a zinc dithizonate complex, in the rat. As soon as 5 min after the i.v. injection of dithizone, degeneration of Paneth cells occurred. At this stage, zinc dithizonate complexes were observed as purple-red granules in bright field microscopy. Thirty to 60 min later, Paneth cells were detached from the basement membrane and shed into the cryptic lumen. After 6 h, the cell debris in the crypts was no longer seen and the crypts once housing Paneth cells were now occupied by neighbouring crypt base columnar cells. Histochemically demonstrable zinc totally disappeared. After 12-24 h, however, definite Paneth cells began to resume. Histochemical staining for zinc was again positive at the apex of these cells. One week after dithizone administration, the number of Paneth cells increased twice as much as in uninjected control and histochemical staining for zinc was highly positive. After 2 weeks, Paneth cell hyperplasia subsided. X-ray microanalysis revealed that zinc was the most abundant metal in Paneth cells. We concluded that chelation of zinc and formation of zinc-dithizone complexes in Paneth cells' cytoplasm would be responsible for the selective degeneration observed after dithizone administration. PMID- 1883742 TI - Genesis of pulmonary foam cells in rats with diet-induced hyper beta lipoproteinaemia. AB - Hyper beta-lipoproteinaemia in rats was produced by feeding a standard diet to which was added excess cholesterol and cholic acid, with or without olive oil, for 4, 8, and 12 weeks. The beta-lipoprotein percentage in serum lipoprotein electrophoresis and lipid contents in very low density lipoprotein and low density lipoprotein fractions in these rats were significantly higher than in the control rats fed the standard diet only. The percentage of foamy monocytes (FMs) to the total number of blood monocytes (BMs) from mononuclear leucocyte fractions and percentage of pulmonary foam cells (PFCs) to the number of alveolar macrophages (AMs) from bronchopulmonary lavage fluids in the rats increased with the extension of the feeding period and were significantly higher than those in the controls. An increase in the percentage of PFCs was closely correlated with that of FMs in the rats. FMs and PFCs had cytoplasmic fine vacuoles proved to be neutral lipid and cholesterol. Histologically, PFCs made an appearance in the lungs of all the rats as early as 4 weeks after the start of feeding. The degree of the PFCs' development increased as the feeding period lengthened. When latex particles were injected intravenously into rats at feeding week 4, the percentage of latex-ingested AMs to the number of AMs in the rats was significantly higher than that of the controls at 4 and 8 days post-injection. The percentage of latex ingested PFCs to the number of latex-ingested AMs increased with the lapse of a day after injection and was significantly higher than that of the controls at 2, 4, and 8 days post-injection. The present findings suggest that the foamy transformation of BMs and their migration into the pulmonary alveoli may be a potential mechanism of the PFCs' development in rats with hyper beta lipoproteinaemia. PMID- 1883743 TI - Electron microscopy of rat lung following a single acute exposure to perfluoroisobutylene (PFIB). A sequential study of the first 24 hours following exposure. AB - The histopathology of rat lung has been studied after an acute exposure to perfluoroisobutylene (PFIB) at a concentration of 638 mg/m3 (78 p.p.m.) for 1.5 min giving a Ct = 957 mg min/m3 for the first 24 h following exposure. Within 5 min of exposure changes to the bronchioles and peribronchial alveoli were observed which took the form of alterations to cilial structure, increased pinocytosis and electron lucency, with occasional vesicle formation of type I alveolar epithelial cells. Intercellular leakage with minimal fluid accumulation in the alveolar spaces was also seen. The very rapid action of PFIB strongly suggests a direct action by the compound. There then followed the gradual development of pulmonary oedema which was visible histologically 2-3 h post exposure with deaths occurring from 7 h onwards. Animals sacrificed at 24 h post exposure showed evidence of widespread pulmonary oedema and alveolar interstitial infiltration by lympho-mononuclear cells and macrophages. PMID- 1883744 TI - Pathological changes in the brains of mice infected with Toxoplasma gondii: a histological, immunocytochemical and ultrastructural study. AB - The pathological changes in the brains of mice infected with T. gondii were studied at various intervals between 7 days and 22 months post-infection using histology, immunocytochemistry and electron microscopy. Initially, a few single parasites were observed (day 7) but necrotic lesions and microglial and inflammatory nodules rapidly appeared (9-I4 days). The majority of the lesions between days 9 and I4 contained proliferating toxoplasma and early cyst formation but from 2I days onwards the vast majority of nodules contained neither parasites nor Toxoplasma antigen. Intact intracellular cysts persisted throughout the period of study eliciting no host response. A generalized meningoencephalitis developed by day II and persisted with varying degrees of severity throughout the 22 months studied. At first, the inflammatory cells consisted of lymphocytes and monocyte/macrophages but during the chronic phase plasma cells predominated. In chronic infections, the number of microglial/inflammatory nodules was relatively constant with only a few containing toxoplasmic material resulting from recent cyst rupture. A few brains contained small nodules of dystrophic calcification. This study shows that in these asymptomatic animals, the major feature is perivascular cuffing by mononuclear cells and localized microglial/inflammatory nodules. After the development of the chronic state, there is no obvious increase or decrease in the severity of the pathological changes with time. PMID- 1883745 TI - Epithelial cell type, clinical behaviour and AgNOR counts in thymic epithelial tumours. AB - The relationship between epithelial cell type, clinical behaviour and number of nucleolar organiser regions (AgNORs) was investigated in 37 thymomas and three thymic carcinomas. The thymomas were classified according to epithelial cell morphology as cortical (16 cases), medullary (8 cases) or mixed (13 cases). Seven cortical tumours had infiltrated the capsule or adjacent structures at the time of operation, whereas only one medullary and two mixed tumours showed evidence of invasion, the differences being statistically significant (P less than 0.01). None of the patients with medullary thymoma had myasthenia gravis, but there was a significantly higher incidence (P less than 0.001) among those with cortical or mixed tumours (six and three cases respectively). The mean AgNOR count for medullary tumours was 1.56, compared with 2.22 and 2.06 for cortical and mixed tumours. Although the counts for medullary tumours were significantly lower than for the other two types (P less than 0.01), there was considerable overlap. The mean count for the carcinomas was 4.94--significantly higher than for the thymomas (P less than 0.01)--but again overlap was considerable. No relationship was demonstrable between AgNOR counts, clinical stage, incidence of myasthenia or recurrence. It is concluded that although classification of thymomas based on epithelial cell type represents an improvement on previous classifications, it must be applied with caution. Similarly, AgNOR counts may give some indication of malignant potential, but their usefulness in individual cases is doubtful. PMID- 1883746 TI - Follow-up study on bone marrow reticulin fibrosis in AML. AB - Planimetric analysis of argyrophilic (reticulin) fibers of the bone marrow was performed on 17 patients (7 males, 10 females, median age 52 years) with acute myeloid leukemia (AML). Trephine biopsies were investigated at presentation and during the course of chemotherapy. Density of reticulin was determined by examining the total marrow area as well as the hematopoietic tissue. In about half of the patients with FAB-subtypes M4, M5 an increased amount of fibers was recognizable on admission in comparison with age-matched controls. Two to five bone marrow biopsies (total 81) of each patient were obtained at intervals ranging mostly between three and seven weeks after cytotoxic treatment. The following results could be demonstrated: in several patients with a normal or elevated fiber count at onset, partial and complete remission was characterized by an increase in reticulin in the regenerative hematopoietic tissue. On the other hand, a relapse was most frequently heralded by a reduction of the formerly increased amount of fibers. Because of the inverse relationship between the density of argyrophilic fibers and the amount of fat cells, these findings were observable only by considering the hematopoietic tissue and not the total marrow area, as has been done in previous studies. For this reason a significant decrease in reticulin fibers in the areas of regenerative hematopoiesis may be suggestive of an impending relapse of AML. PMID- 1883747 TI - Analysis of rare high-DNA cell populations in serous effusions using continuous motion imaging. AB - The rare high-DNA cell sub-populations in a series of serous effusion specimens were analysed to determine whether such measurements could provide a basis for the improved diagnosis of malignancy. Monolayer specimens stained with gallocyanin chrome-alum were scanned with the CERVIFIP continuous-motion image analyser to locate and measure the highest-DNA cells in the sample. Two types of features were obtained for the detected sub-populations; firstly, 'percentile ploidy' values which characterise the ploidy levels above which specified proportions of the total cells are found; and secondly 'percentage abnormal' values which characterise the proportion of the cells diagnosed as malignant during examination by a cytopathologist. The classification accuracy for one or both of these features was then obtained by comparison with the clinical outcome of each patient. The results gave a classification error of 9/44 (20%) using the 0.01% percentile ploidy alone, 6/44 (14%) using the 75% percentage abnormal feature alone, but only 2/44 (5%) from a box discriminant using both features. It was therefore concluded that the analysis of the high-DNA cell population could be of value in the diagnosis of malignancy in serous effusion specimens. PMID- 1883748 TI - An image analysis method for assessment of prognostic risk in prostate cancer: a pilot study. AB - Fully automated computerized image analysis at medium resolution (1 micron per pixel space) was applied in a study of 17 patients with stage D1 prostate cancer. For this pilot study, patients were selected on the basis of very good or very poor outcome. This selection was made in the hope of identifying morphometric features that are useful in prognostic assessment. Nine patients with good outcome were alive after 7 or more years of follow-up and eight patients with poor prognosis were dead of disease in less than 3 years. All patients were treated with 125I seed implantation to the prostate and pelvic lymph node dissection. Hormone therapy was not administered until the time of distant failure. Routine hematoxylin and eosin tissue sections of lymph nodal tissue bearing metastatic neoplasm were used for this analysis. A minimum of eight scenes per case was analysed. Of 50 measured parameters on each cluster, five (gray level distribution, number of cell clusters per scene, bending energy, average cluster area and cluster polarity) were useful to distinguish patients with good outcome from those with a poor outcome. Thirteen of the 17 patients were correctly classified by image analysis (P = 0.044, Fischer's exact test). By comparison, flow cytometry of the identical tissue samples correctly classified 14 of 17 patients (diploid, good outcome; aneuploid, poor outcome; P = 0.009). Only one patient was incorrectly classified by both image analysis and flow cytometry, implying a complementary prognostic role for the two methods. The encouraging result, successful identification of useful morphometric features, justifies a larger study of unselected patients. PMID- 1883749 TI - HOME: Highly Optimized Microscopic Environment (a new workstation for microscopic analysis in pathology). PMID- 1883750 TI - Selected bibliography. PMID- 1883751 TI - Speech patterns and satisfaction in diagnostic and prescriptive stages of general practice consultations. AB - With a general goal of establishing indicators of the quality of the helping relationship within medical consultations, we recorded and analysed verbal interactions in general practice consultations, in two studies. The diagnostic and prescriptive stages of the consultation were analysed separately, first with doctor satisfaction as the outcome and then, with a second sample of doctors, with both doctor and patient satisfaction as outcomes. Patients and doctors were found to have somewhat different views of what made a highly satisfactory consultation. The most satisfying consultations for doctors were those in which the medical problem and its solution seemed clear; patients felt most satisfied with consultations where they had discussed their own experiences and opinions during the second, prescriptive stage of the consultation. PMID- 1883752 TI - Fear of dependence in therapeutic relationships. AB - The fear of dependence is considered as it is experienced by therapists and patients in therapeutic relationships. The concept of dependence is briefly reviewed in the psychoanalytic literature of both East and West. A clinical illustration is given of the fear of dependence in a male patient. It is suggested that the Western ideal of independence is a myth which especially ignores the reliance on internal others. PMID- 1883753 TI - Psychological research on the martial arts: an addendum to Fuller's review. AB - Most psychological research on the martial arts has been conducted from a positivist stance, and Fuller's (1988) review of research reflected a positivist tone while suggesting that therapeutic influences may be achieved from martial arts training methods abstracted from their traditional setting. This addendum cites two important contextual problems influencing martial arts research. First, the martial arts are influenced by Oriental styles of thinking such as Taoism and Zen Buddhism that are difficult to grasp from a Western positivist point of view. We suggest that phenomenology seems to have some stylistic parallels with Oriental thinking and appears to offer the Westerner a point of entry toward understanding the martial arts as Oriental arts. Second, the cultural and psychological values and meanings of the Oriental martial arts may change when situated in a Western context, thus changing their method, content, and therapeutic influence. We suggest that a non-positivist and context-sensitive approach such as phenomenology might clarify the contextual intricacy of the martial arts and thereby facilitate improved theoretical foundations and empirical research of martial arts participation as a psychological phenomenon. PMID- 1883754 TI - Evidence that defence mechanisms are more related to personality than to symptoms. AB - The Defense Mechanisms Inventory is one of the more popular instruments for examining hypothetical dynamic mechanisms. It is known to correlate with some measures of personality and mood. We proposed that, as measures of personality and measures of defence mechanisms are considered to have a common origin in early experience, they should be more strongly correlated than measures of mood, given equal power in the measures of the dependent variables. In this connection we report the relationship which were found between scores on the subscales of the Inventory and the Hysteroid/Obsessoid Questionnaire and the Hospital Anxiety and Depression Scale. There was only a weak relationship between anxiety or depression on the one hand and the Defense Mechanisms Inventory on the other. The highest correlation noted in this regard was Pearson's r = .18, p = .065 between anxiety and the scale Turning Against Self (TAS). The Hysteroid/Obsessoid Questionnaire showed a positive relationship between high scores (hysteroid, i.e. extraverted) and the scale TAO (Turning Against the Object) and a negative relationship for the TAS scale (r = -.290, p = .003). Thus the Defense Mechanisms Inventory showed a stronger relationship with personality than with mood. PMID- 1883755 TI - Social support and psychological distress in women and men. AB - The relationship between psychological distress and social support was investigated, along with various other health-relevant variables, in a nationally representative sample of some 2050 women and 1873 men, who also returned the self completion questionnaire in the 1984-85 British Health and Lifestyle Survey. Psychological distress was measured with the 30-item General Health Questionnaire. Stepwise regression analyses indicated that the quality of family support accounted for a significant increase of 0.2-1.0 per cent of the variance in the GHQ for women and 0.8-1.9 per cent for men. The correlation between family support and distress was reduced from -.13 to -.04 for women and from -.15 to .10 for men when all other variables were partialled out. It was highest (-.33) for the better qualified women and men in the youngest (18-24) age group. PMID- 1883756 TI - Infants born at risk: consequences for maternal post-partum adjustment. AB - The role of infant risk and social support as predictors of post-partum adjustment was investigated. Fifty-three mothers whose infants reflected the range of neonatal conditions were interviewed six weeks after discharge of their infant from hospital. They were assessed on measures of emotional distress, depressive symptoms, social support and perceptions of, and concerns about, their infant and themselves. The results indicated that mothers of higher risk infants reported higher levels of emotional distress and depressive symptomatology, more concerns about themselves and their baby, more difficulty in expressing affection towards their baby and greater dissatisfaction with their social support. Using multiple regression techniques, depressive symptoms were predicted by neonatal risk and dissatisfaction with social support from family and friends, while emotional distress was predicted by neonatal risk and dissatisfaction with social support from the infant's father. The study underlines the need to place more emphasis on infant variables as factors in maternal post-partum adjustment. PMID- 1883757 TI - Treatment of a 15-year-old girl with chronic muscle-contraction headache using implosive therapy. AB - A 15-year-old girl with chronic muscle-contraction headache was treated initially using a behaviourally based headache programme. Little change in headache activity resulted. Implosive therapy was incorporated into treatment after the girl revealed a past episode of sexual abuse. A substantial reduction in headache activity was noted at post-treatment and follow-up. PMID- 1883758 TI - Moderate levels of chronic mood disturbance are associated with increased cognitive complexity about the self. AB - Despite its status as a general assumption, the idea that mood disturbance is associated with reduced complexity of cognitive representations has received little in the way of empirical support. It is suggested that this may arise because of a failure to make distinctions concerning the severity and type of mood disturbance, as well as not being specific about what the representations actually refer to. Using repertory grid methodology (Bieri et al., 1966) with a group of moderately mood-disturbed 'worriers', results showed that this group are significantly more complex than matched controls, but only for representations concerned with themselves. Moreover, this was related to chronic rather than current mood disturbance. The results are interpreted as indicating that cognitive complexity may follow an inverted-U pattern, where the self representations of severely mood-disturbed and control subjects, although differing in valence, are similar in their lack of complexity. On the other hand, those who are chronically but moderately disturbed are, as a result of their ongoing tendency towards introspection, more complex in their self representations. Possible implications for vulnerability to emotional disorder are discussed. PMID- 1883759 TI - The environmental intergenerational transmission of alcohol problems: a comparison of two hypotheses. AB - Two competing hypotheses concerning the mechanism of transmission of excessive substance use from one generation to the next are tested, using data from a study of 16- to 35-year-old offspring of problem-drinking parents. The 'positive influence' hypothesis predicts that the more positive has been the offspring's relationship with the problem-drinking parent during upbringing, the greater the risk of excessive drinking or drug taking in young adulthood. This hypothesis received support only for women with fathers with drinking problems. The 'relationship deficiency' hypothesis predicts that those offspring most at risk are those who have had the more negative relationships with parents. This hypothesis received some support in the case of men with mothers with drinking problems: this subgroup of offspring were more at risk if they reported having had poor relationships with their fathers. It is concluded that the environmental intergenerational transmission of problems of excessive substance use occurs via a variety of mechanisms which are likely to be of differential importance in different subgroups. PMID- 1883760 TI - Death of an institution. AB - The impact on an institution of the death of its leader is examined. The vulnerability to loss and change that was engendered and the decline and eventual demise of the organization is described. A way of understanding the process of grief in institutions, drawing on psychoanalytic, attachment and systems theory, is proposed. PMID- 1883761 TI - Cholinergic amacrine neurons of the dogfish retina. AB - In the mammalian retina, the dendritic arbors of cholinergic amacrine neurons have a unique starburst shape; these arbors lie in narrow sublaminae within the inner plexiform layer, where they provide input to a wide variety of ganglion cell types. Immunocytochemistry has been used to identify cholinergic cells in one poikilotherm, the goldfish (Tumosa et al., 1984), but there has been no description of the detailed dendritic morphology of these cells in the lower vertebrates. In the present study, cholinergic neurons have been characterized, by immunocytochemistry and dye filling, in the retina of the Pacific Coast dogfish, Squalus acanthias. The inner nuclear layer contained two populations of choline acetyltransferase-immunoreactive amacrine cells, of different sizes (average soma diameters 12.2 vs. 16.3 microns); 70% of the immunoreactive cells were of the smaller type. Cholinergic dendrites from these two cell populations formed two narrow strata within the inner plexiform layer, at depths of 14% and 31%. In the ganglion cell layer, 40% of the cells were immunoreactive for choline acetyltransferase (ChAT); these cells were very homogeneous in size, had an average diameter of 12.6 microns, and appeared to represent a single class of cholinergic amacrine. The dendrites of these cells formed a single, narrow stratum within the inner plexiform layer, at a depth of 59%. In living preparations, the smallest cell bodies in the ganglion cell layer were filled iontophoretically with Lucifer Yellow, under microscopic control. Such cells invariably had a stellate morphology; in many cases, they appeared quite similar to the starburst cholinergic amacrine cells described in rabbit and rat (Vaney, 1984; Voigt, 1986). Although double-label experiments failed to demonstrate ChAT immunoreactivity in specific dye-filled cells, the dendritic arbors of individual dye-filled stellate dogfish amacrines did co-stratify precisely with the proximal ChAT-immunoreactive sublamina of the inner plexiform layer. In addition, dye injection and ChAT immunocytochemistry appeared to label the same population of dogfish neurons, as suggested by the close structural similarity, and similar numerical proportion, of the cells identified with these two techniques. Similarities between the displaced cholinergic amacrine neurons of the dogfish retina, and the cholinergic, "starburst" amacrine neurons of the rabbit retina, are discussed. PMID- 1883762 TI - Impaired visual thresholds in hypopigmented animals. AB - Ocular hypopigmentation is associated with neurological defects in structure and function. This paper investigates the absolute visual thresholds in dark-adapted hypopigmented animals compared to their normally pigmented controls. Here we asked (1) whether the threshold elevation found in hypopigmented animals is a general consequence of the reduction in melanin content; (2) if so, which melanin components in the eye are likely to influence visual thresholds; and (3) whether similar threshold defects can be detected in orders other than rodents. By single unit recordings from the superior colliculus, we compared incremental thresholds of normal black mice of the C57BL/6J strain to hypopigmented mutants: beige (bg/bg), pale ear (ep/ep), and albino (c2J/c2J) mice, three mutants in which melanin pigment throughout the body is affected; and Steel (Sl/Sld) and dominant spotting/W-mice (W/Wv), two mutants with normal pigmentation in the retinal pigment epithelium (RPE) but without any melanin in the choroid or the rest of the body. We found that all mutants had elevated thresholds that varied with the reduction in melanin. The albinos were 25 times less sensitive than black mice, pale ear mice 20 times, beige mice 11 times, and Steel and W-mice 5 times. The mean thresholds of dark-adapted black mice were 0.008 cd/m2. Recordings from rabbits showed a similar impairment of visual sensitivity; incremental thresholds were elevated 40 times in New Zealand-White albino rabbits (0.0008 cd/m2) compared to Dutch-Belted pigmented controls (0.00002 cd/m2).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1883763 TI - Evidence for two systems mediating perceived contrast. AB - We report psychophysical evidence for a categorical dichotomy in the perception of contrast. Observers were required to rate the contrast of sinusoidal gratings (2.3 c/d) with contrast varying over a given range relative to two standards. One standard was designated "high" contrast and the other was designated "low." There was a boundary effect: contrast judgment depended upon whether the tested ranges included 10-15% contrast and discrimination was sharpest at the boundary between 10 and 15% contrast. These results are consistent with the existence of two systems underlying perceived contrast; one primarily sensitive below 10%, and the other primarily sensitive above 15% contrast. PMID- 1883764 TI - Behavioral and electrophysiological sensitivity to temporally modulated visual stimuli in the ground squirrel. AB - Behavioral and electrophysiological methods were used to measure sensitivity to flickering lights in a dichromatic species, the California ground squirrel (Spermophilus beecheyi). Discrimination tests were used to determine spectral sensitivity at stimulus frequencies from 5-50 Hz and increment threshold spectral sensitivity. The contributions of retinal mechanisms to these capacities were assessed by recording the responses of optic nerve fibers to temporally modulated monochromatic lights. In the ground squirrel, as in the human, the shape of the spectral-sensitivity function depends on the temporal frequency of the stimulus. Results from single-unit recording show that all of the classes of optic nerve fibers in the ground squirrel are highly phase-locked to the stimulus for modulation rates as high as 50 Hz. Neither the responses of photoreceptors nor any class of optic nerve fiber can singly account for the behavioral results. The electrophysiological results are also counter to models which propose that temporally dependent changes in the spectral sensitivity of spectrally opponent fibers account for the behavior. The temporal resolution of the optic nerve fibers exceeds that of the behaving animal suggesting that retinal mechanisms do not limit behavioral temporal resolution. PMID- 1883765 TI - Experimental stray light in retinal densitometry. AB - The effects of stray light upon retinal pigment densitometric measurements were evaluated by adding specified amounts of stray light to fundus reflections. To allow for interpolations and extrapolations, a computer simulation was devised and validated against the empirical data. The results demonstrate that measured density is greatly decreased by increases in stray light but the time constant of pigment regeneration is little affected. PMID- 1883766 TI - Fine structure of receptive-field centers of X and Y cells of the cat. AB - We investigated the fine structure of receptive field centers of X and Y cells of the retina and lateral geniculate nucleus of the cat using sinusoidal grating stimuli of high spatial frequency. By measuring orientation tuning and spatial frequency tuning at multiple orientations, the two-dimensional sensitivity distribution was examined. We found that receptive-field centers typically have multiple sensitivity peaks that can be modeled as several spatially offset subunits. A subunit structure was found in both X and Y cells, with an average number of subunits per receptive-field center of approximately 2.9 in X cells and approximately 4.6 in Y cells. In X cells these subunits may correspond to individual cone bipolar inputs. In Y cells, the subunits may reflect the structure of the dendritic tree. The observation of the subunit structure of the receptive-field center, in conjunction with manipulation of the retinal wiring through pharmacological intervention, may provide a new tool for probing the circuitry of the retina. PMID- 1883767 TI - Rod bipolar cells in the cone-dominated retina of the tree shrew Tupaia belangeri. AB - The tree shrew has a cone-dominated retina with a rod proportion of 5%, in contrast to the common mammalian pattern of rod-dominated retinae. As a first step to elucidate the rod pathway in the tree shrew retina, we have demonstrated the presence of rod bipolar cells and studied their morphology and distribution by light and electron microscopy. Rod bipolar cells were labeled with an antiserum against the protein kinase C (PKC), a phosphorylating enzyme. Intense PKC immunoreactivity was found in perikarya, axons, and dendrites of rod bipolar cells. The cell bodies are located in the sclerad part of the inner nuclear layer, the dendrites ascend to the outer plexiform layer where they are postsynaptic to rod spherules, and an axon descends towards the inner plexiform layer (IPL). The axons branch, and terminate in the vitread third of the IPL where mammalian rod bipolar cells are known to terminate. Two amacrine cell processes are always seen as the postsynaptic elements (dyads). Dendritic and axonal arbors of rod bipolar cells are rather large, up to 100 microns in diameter. The topographical distribution of the rod bipolar cells was analyzed quantitatively in tangential sections. Their density ranges from 300 cells/mm2 in peripheral retina to 900 cells/mm2 more centrally. The distribution is rather flat with no local extremes. Consistent with the low rod proportion in tree shrew, the rod bipolar cell density is low compared to the rod-dominated cat retina for example (36,000-47,000 rod bipolar cells/mm2). Rod-to-rod bipolar cell ratios in the tree shrew retina range from smaller than 1 to about 7, and thus are also lower than in cat. PMID- 1883768 TI - Diurnal control of rod function in the chicken. AB - We studied rod function in the chicken by recording corneal electroretinograms (ERGs). The following experiments were performed to demonstrate rod function during daytime: (1) determining the dark-adaptation function; (2) measuring the spectral sensitivity by a a-b-wave amplitude criterion in response to monochromatic flickering light of different frequencies ranging from 6.5-40.8 Hz (duty cycle 1:1); (3) analyzing the response vs. log stimulus intensity (V-log I) function in order to reveal a possible two phase process; and (4) determining the spectral sensitivity function either in a non-dark adapted state or after dark adaptation of the animals for 1 and 24 h. None of these experiments demonstrated clear evidence of rod function during daytime. On the other hand, we found rods histologically by light- and electron microscopy. Therefore, we repeated our ERG recordings during the night (between midnight and 3:00 A.M.). Without previous dark adaptation, rod function could be seen immediately in the same experiments described above. The result shows that, in the chicken, rods are turned on endogenously during the night but are scarcely functional during the day. PMID- 1883769 TI - Spinal anesthesia for cesarean delivery with dilute solutions of plain bupivacaine: the relationship between infused volume and spread. AB - In a prospective open study, 40 women received spinal anesthesia for cesarean delivery induced with 15 mg glucose-free bupivacaine administered in dilutions of 0.5% (3 ml), 0.25% (6 ml), 0.125% (12 ml) and 0.083% (18 ml). The solutions were infused over 30 minutes while the women lay in the right lateral decubitus. No clinical or statistical difference in the final level of block was observed between the groups. All the solutions behaved as if slightly hypobaric with the development of essentially unilateral blocks during the infusion period. At the end of the infusion period when the women were turned from the lateral decubitus to a supine tilted position, there was a sudden rise in the levels of block on both sides of the body such that, by ten minutes after turning, there was no discernible difference between the two sides. The final block levels attained were within the expected range for conventional spinal anesthesia using 2.5-3.0 ml glucose-free 0.5% bupivacaine. The findings suggest that the subarachnoid spread of isobaric/hypobaric spinal anesthetic drugs is a complex process unlikely to be explained by reference to simple models of the spinal curves. PMID- 1883770 TI - The addition of 0.2 mg subarachnoid morphine to hyperbaric bupivacaine for cesarean delivery: a prospective study of 856 cases. AB - In an effort to determine the incidence of respiratory depression and other side effects of subarachnoid morphine, we conducted the following prospective study in a large number (856) of young female patients undergoing cesarean delivery in one hospital. During the period from July 1987 to January 1989, patients receiving subarachnoid hyperbaric bupivacaine combined with 0.2 mg preservative-free morphine were included. They were continuously monitored for 24 hours using a pulse oximeter. For 24 hours, the vital signs, including respiratory rate every hour, and the side effects, including pruritus, nausea, and vomiting, were recorded. The need for analgesia and the total dose of opioids during the first 24 hours were documented. Our results showed that respiratory depression (SaO2 less than or equal to 85% and/or respiratory rate ten breaths per minute or less) occurred in eight patients, all of whom were markedly obese. Fifty-eight percent of the patients did not require analgesics for 24 hours. In those requiring an added opioid, the dose was (9.1 +/- 0.5 mg morphine, mean +/- SEM). Eighty-five percent of the patients were satisfied with the postoperative analgesia. Six percent were dissatisfied due to the side effects, i.e., pruritus, nausea and/or vomiting. Nine percent were dissatisfied with the pulse oximeter because it caused false alarms and limited their mobility. PMID- 1883771 TI - Analgesia after cesarean delivery: patient evaluations and costs of five opioid techniques. AB - The study was designed to compare five opioid analgesic regimens administered after cesarean delivery in a routine hospital setting with respect to patients' perceptions of their pain relief and the impact of analgesic technique on recovery and hospital costs. After cesarean delivery, 684 patients received one of the following: epidural morphine, alone (EM,n = 128), or with fentanyl (EM + F,n = 245); subarachnoid morphine (n = 48); intramuscular meperidine (n = 165), or patient-controlled analgesia using meperidine (PCA, n = 98). On the first three postoperative days (Days 1-3; day of operation is Day 1) patients were surveyed regarding their impressions of their analgesia, the incidence of side effects, times to resume normal activities and satisfaction with their technique. Information regarding drug interventions and costs was obtained from anesthetic records and nursing charts. Patients receiving intramuscular and PCA opioids reported significantly more severe pain during the first 16 hours than those receiving intraspinal opioids (p less than 0.05); differences were minimal for the remainder of Day 1. Among the intraspinal groups, analgesia was best overall with EM; specifically, fentanyl did not decrease early postoperative pain. Analgesia with PCA and intramuscular opioids was similar during the first 16 hours; however, PCA patients felt they had less pain thereafter. Side effects were common in all intraspinal groups and were least frequent with PCA (p less than 0.05 versus all intraspinal groups). Times to sit, walk and drink were similar in all patients except those receiving intramuscular opioids after general anesthesia, who experienced a several-hour delay. Other aspects of recovery did not differ among the groups. Satisfaction parallelled pain relief and was better with intraspinal than with systemic opioids. Costs were greatest with PCA, although differences were small (less than 1%) relative to total hospital charges. PMID- 1883772 TI - Sensory analgesia for vaginal deliveries: a preliminary report of continuous spinal anesthesia with a 32-gauge catheter. AB - Our initial experience in providing pain relief during labor and delivery for 20 parturients using a 32-gauge continuous spinal microcatheter using 1% lidocaine is described. The technique significantly reduced the pain of labor, which was assessed as severe by 18 of the patients, and provided adequate perineal anesthesia for vaginal delivery with 18 patients indicating pain during delivery to be minimal. The major advantage of continuous spinal anesthesia is the ability to rapidly establish sensory anesthesia with the flexibility to reinject additional local anesthetic should a complete sensory or sensory and motor block be required for forceps or cesarean delivery. Technical difficulty was the main disadvantage with the use of the 32-gauge microcatheter. An inability to thread the catheter (two patients) through the 26-gauge spinal needle or kinking of the catheter (two patients) making injection impossible, and unintentional catheter removal (one patient) resulted in a 25% failure rate with this technique. PMID- 1883773 TI - Continuous 2-chloroprocaine infusion versus intermittent bolus injections of bupivacaine or 2-chloroprocaine for epidural anesthesia in cesarean delivery. AB - A continuous infusion of 2-chloroprocaine (Group C) was compared with intermittent bolus injections of bupivacaine (Group B) or 2-chloroprocaine (Group N) for epidural anesthesia in cesarean delivery. Sixty-six patients scheduled for elective cesarean delivery were studied retrospectively during a three-month period. Maternal and neonatal demographics; cord pH; Apgar scores; duration of surgery, including times from induction, incision and end of the case; fluid requirements in the operating room and recovery room; amount of ephedrine used; blood pressures; duration of analgesia, and meperidine use via patient-controlled analgesia (PCA) up to 48 hours postpartum were recorded. Group B experienced a significantly longer time from loading dose to incision and a longer duration of analgesia, but twice the duration of recovery room care than either of the 2 chloroprocaine (2CP) groups. In the first six hours after surgery, Group N patients required significantly more PCA injections than patients in either Group B or Group C. Although statistically significant changes were detected in blood pressure values at three intervals, no clinical importance was appreciated. Fluid requirements were also greater for patients in Group B, both intraoperatively and in the post-anesthesia care unit. Epidural anesthesia using continuous 2CP infusion appears to combine the beneficial effects of bolus injections of both bupivacaine and 2CP by reducing recovery room stay and PCA requirements without troublesome side effects. PMID- 1883774 TI - Training anesthesia personnel to perform bleeding times. AB - Template bleeding time results generated by residents in anesthesiology correlate well with those obtained by trained laboratory personnel (p less than 0.002). Anesthesia personnel can accurately perform bleeding time tests when laboratory support is not available. The results of these tests can be used to guide clinical decisions. PMID- 1883775 TI - Long duration local anesthesia with lecithin-coated microdroplets of methoxyflurane: studies with rat skin. AB - Lecithin-coated microdroplets of methoxyflurane (MOF) are shown to produce local anesthesia of three- to six-day duration in the skin with a single intradermal injection in rats. Anesthesia was quantitated by elevation of the threshold (milliampere) for shock vocalization with intradermal electrodes. Intradermal injection of 0.1 ml 0.5% MOF gave moderate (2.1 mA) anesthesia of approximately three-day duration for a 10-12-mm diameter area, with no damage to the tissue. Higher concentrations gave six-day duration anesthesia at very high level (7 to 12 mA) anesthesia of three- to five-day duration with some damage to the tissue. At 4.4% MOF, ulcers formed in the center of the injection site with maximal dimensions of 1.3 mm (11-13% of the site diameter). Phenol, a widely used neurolytic agent, was tested as a control in the same concentration range. Phenol at 4.4% gave very high level (8 mA) anesthesia for longer than seven-day duration and caused formation of ulcers with maximal dimensions of 3.8 mm (31-38% of the site diameter). Analysis showed that MOF produced less damage than phenol for any given degree of anesthesia. Systemic toxicity and pharmacokinetic data are also presented. Phenol produced a hypothermic reaction and behavioral changes, whereas MOF was without systemic effect. The plasma concentrations of phenol were four to five times greater than those of MOF. These results suggest that MOF may have clinical advantages over phenol. PMID- 1883776 TI - Long duration local anesthesia with lecithin-coated microdroplets of methoxyflurane: studies with human skin. AB - Lecithin-coated microdroplets of methoxyflurane (MOF) have been reported to produce local anesthesia of long duration in rats. The present study was conducted in two phases. The first phase was open label studies in two human volunteers aimed at determining the effective concentration of MOF in human skin. Over the concentration range of 0.3-2.4%, MOF produced local anesthesia to pinprick and cold stimuli within 15 seconds. The duration of the anesthesia effect of 2.4% MOF in the skin of the buttock, forearm and leg was five to eight days. Microdroplets containing isoflurane, a more volatile agent, gave an anesthetic effect that reversed within two to five hours. In the second phase of the study, the safety and efficacy of MOF were compared to phenol in placebo controlled and blinded studies using indwelling stimulating electrodes. Phenol was destructive to skin at a concentration necessary to obtain a degree of local anesthesia comparable to MOF. The greater part of the anesthetic effect produced by phenol at this "toxic" concentration was transient (approximately one hour). In contrast to phenol, MOF produced an anesthetic effect lasting four to seven days without producing visible damage to skin. These results suggest that MOF is safer and more efficacious than phenol for producing long-lasting local anesthesia of human skin. PMID- 1883777 TI - Uniform Requirements for Manuscripts Submitted to Biomedical Journals. International Committee of Medical Journal Editors. AB - In the 12 years since it was first published, the "Uniform Requirements for Manuscripts Submitted to Biomedical Journals" (the Vancouver style), developed by the International Committee of Medical Journal Editors, has been widely accepted by both authors and editors; more than 400 journals have stated that they will consider manuscripts that conform to its requirements. This is the fourth edition of the Uniform Requirements. PMID- 1883778 TI - Myoclonus of hand and arm after ipsilateral stellate ganglion block. PMID- 1883779 TI - Drug interactions in bupivacaine-induced cardiotoxicity. PMID- 1883780 TI - Use of the nerve stimulator in teaching regional anesthesia techniques. PMID- 1883781 TI - Similarity between ephedrine and atropine ampules. PMID- 1883782 TI - Quality of the perinatal autopsy. PMID- 1883783 TI - Management of tubal infertility in the 1990s. PMID- 1883784 TI - West Midlands perinatal mortality survey, 1987. An audit of 300 perinatal autopsies. AB - As part of the West Midlands regional perinatal mortality survey an audit of perinatal autopsies was performed in 10 of 20 districts in the region. Autopsy reports were available from 300 of the 426 deaths (70%) reported in these districts. These were coded for 8 aspects including the clinical summary, body measurements, descriptive content, organ weights, post mortem radiology and microbiology, histology and other relevant investigations e.g., biochemistry, cytogenetics. Overall 44% of the autopsies failed to attain an arbitrary minimum score of 300, the mean score being 299. Excluding those autopsies performed at the regional centre these figures were 50% and 268 respectively. These data indicate that a high autopsy rate does not necessarily reflect a high quality of service and further emphasise the concerns that have been expressed by obstetricians, paediatricians, geneticists, parents and parliamentarians about the perinatal pathology services in the United Kingdom. PMID- 1883785 TI - An analysis of factors influencing the outcome of 232 consecutive tubal microsurgery cases. AB - A consecutive series of 232 tubal microsurgical operations performed at the Jessop Hospital for Women, Sheffield, between 1983 and 1989, was analysed. The various contributory factors to tuboperitoneal damage were reviewed. Eighty patients (35%) conceived, resulting in 66 (29%) live births and 14 (6%) miscarriages. A further 12 (5%) had ectopic pregnancies. The overall cumulative conception rate (CCR) was 40% at the end of 50 months. Microsurgery has been most successful in the adhesiolysis group (n = 78) with a CCR of 46% at the end of 50 months. The terminal salpingostomy group (n = 97) had a CCR of 40% at the end of 36 months. There was a significant reduction in the live birth rate for the group with hydrosalpinx greater than 20 mm in diameter compared with the group with less than 20 mm (P = 0.05). The proximal anastomosis group (n = 27) had a CCR of 33%. No pregnancy was reported following reconstructive surgery for multiple occlusion sites. Overall, the extent of pelvic adhesions had a significant influence on the outcome (P = 0.02). The likelihood of conception was significantly influenced by the duration of infertility (P = 0.02) but not affected by the aetiology of tuboperitoneal damage, parity or age of the patient. In our hands, tubomicrosurgery is more cost-effective than in-vitro-fertilization as a primary treatment of infertility due to tubal diseases. PMID- 1883786 TI - Is GIFT (gamete intrafallopian transfer) the best treatment for unexplained infertility? AB - OBJECTIVE: To compare the cumulative pregnancy rates after gamete intrafallopian transfer (GIFT) with the cumulative spontaneous pregnancy rates in couples with unexplained infertility. DESIGN: A contemporaneous study in a single group of patients. SETTING: Northern Regional Fertility Centre. SUBJECTS: 76 couples with unexplained infertility of more than 3 years duration. INTERVENTIONS: Successful pregnancies were recorded during at least 3 months before GIFT and up to 21 months after a maximum of three cycles of GIFT treatment. MAIN OUTCOME MEASURES: Pregnancy resulting in a live birth. RESULTS: Average monthly fecundability without treatment was 0.021 and after GIFT was 0.14 (P less than 0.001). This was reflected as a cumulative pregnancy rate of 52% after three cycles of GIFT and 30% after 24 months without treatment. CONCLUSIONS: The chance of having a baby after one cycle of GIFT is significantly greater than the chance in a spontaneous cycle. However, considering the cumulative pregnancy rates, we suggest that if GIFT is to be a realistic treatment option, it should be offered for more than one cycle. PMID- 1883787 TI - Placental bed spiral arteries in the hypertensive disorders of pregnancy. AB - OBJECTIVE: The investigation of the histology of the placental bed spiral arteries in normal pregnancy and in pregnancies complicated by hypertension, with or without proteinura. DESIGN: An observational study, based on women having caesarean sections for clinical reasons. SUBJECTS: 17 normal pregnant women, 43 with gestational hypertension, of whom 39 had proteinuria, 17 with chronic hypertension, of whom 6 had proteinuria, and 5 with unclassified hypertension. INTERVENTIONS: Placental bed biopsies obtained during caesarean section. MAIN OUTCOME MEASURES: Histological appearance of sections stained with haematoxylin and eosin PAS and Lendrum's MSB. RESULTS: Biopsies containing spiral arteries were obtained from 6 normotensive and 44 hypertensive women. Trophoblastic invasion was present in 5 of the 6 normotensive biopsies but absent in the majority of those with hypertension. Subintimal proliferation was seen in all the normotensive biopsies but in only 8 of 28 from those with gestational hypertension and proteinuria. Other features seen predominantly or only in the hypertensive biopsies, in order of frequency, were medial hyperplasia, fibrin deposits, acute atherosis, endothelial vacuolation and thrombosis. CONCLUSION: Absence of physiological changes may not be peculiar to preeclampsia but may be associated or even a result of various forms of hypertension in pregnancy. Spiral arteries show a spectrum of changes in hypertensive pregnancies that do not appear to bear a clear-cut relation to the clinical signs. PMID- 1883788 TI - The variation of endometrial response to a standard hormone replacement therapy in women with premature ovarian failure. An ultrasonographic and histological study. AB - The endometrial response to a standard hormone replacement therapy in 18 women with premature ovarian failure was examined by serial ultrasonographic measurement of endometrial thickness and histological study of endometrial biopsy taken on day 19 of the cycle. Women with idiopathic ovarian failure (n = 10) had significantly better response than women with Turner's syndrome (n = 4), whereas women with premature ovarian failure associated with previous chemotherapy (n = 4) had an intermediate response. These observations suggest that the endometria of women with Turner's syndrome responded suboptimally to steroid hormones. However, all endometrial biopsies studied revealed secretory changes. Overall, the results of histological dating of endometrial biopsy were found to be positively correlated with endometrial thickness on day 19 of the cycle (r = 0.72, P less than 0.01). The plasma concentration of oestradiol on days 15, 19 and 29 of the artificial cycle were found to be significantly higher than those on the corresponding days of the natural cycle. PMID- 1883789 TI - The place of oophorectomy at vaginal hysterectomy. AB - A series of 740 vaginal hysterectomies with attempted vaginal oophorectomy is presented and compared with 700 vaginal hysterectomies without oophorectomy. Vaginal oophorectomy was successful in 94% of the patients. Factors influencing the success include obesity, nulliparity, decreased vaginal access and space, lack of uterine descent, increased uterine size and tubo-ovarian disease. These have been analysed and the recognition and management of technical difficulties are described. There was no morbidity attributable to the vaginal oophorectomy. With experience and appropriate technique suitable women can be offered prophylactic oophorectomy at the time of vaginal hysterectomy. PMID- 1883790 TI - Delivery in an obstetric birth chair: a randomized controlled trial. AB - OBJECTIVE: To determine whether nulliparae whose second stage of labour is conducted in an obstetric birth chair have a lower incidence of instrumental delivery than those using a conventional delivery bed. DESIGN: Randomized controlled trial using sealed, opaque envelopes for allocation. SETTING: Delivery ward in a busy teaching hospital. PATIENTS: 1250 nulliparae with a singleton live fetus with cephalic presentation, without epidural anaesthesia, who had achieved full dilatation. INTERVENTION: Intention to conduct second and third stages of labour in either the Birth-EZ chair or the conventional delivery bed, as randomly allocated. MAIN OUTCOME MEASURES: Primary measure: vaginal operative delivery; principal secondary measures: duration of second stage, perineal trauma, blood loss, women's views, and neonatal status. RESULTS: Delivery in the birth chair did not result in a reduction in operative delivery, overall. However, there was a reduction in vaginal operative delivery for fetal heart rate abnormality. There was no beneficial effect on perineal trauma or puerperal perineal pain. Post partum haemorrhage was more frequent in the birth chair group. CONCLUSIONS: Delivery in the birth chair does not offer any obvious advantage to women over delivery on a bed. PMID- 1883791 TI - Partial placenta membranacea. AB - Seven pregnancies complicated by partial placenta membranacea occurring over a 2 year period are described. The condition is encountered more frequently than the total or near-total form, but is similarly associated with recurrent antepartum haemorrhage, miscarriage or preterm delivery. Diagnosis by ultrasound scan may prove difficult. Five pregnancies had histological evidence of chorioamnionitis, which may have helped to precipitate labour; three fetuses showed pulmonary inflammatory changes of at least 2 days' duration. No maternal predisposing factors could be elicited. PMID- 1883792 TI - Autoreactivity in women with endometriosis. AB - Serum samples from 71 patients with laparoscopically staged endometriosis and from 109 age-matched non-pregnant control women were tested for antibodies to nuclear, phospholipid, smooth muscle and sperm antigens. Immunoglobulin G, M and A and complement components C3 and C4 were measured. Prevalence of the following autoantibodies was statistically significantly greater in women with endometriosis than in the control group: antinuclear antibodies, antibodies to ribonucleoproteins, smooth muscle antibodies, lupus anticoagulant and anticardiolipin antibody. Forty-one women with endometriosis (58%) had some type of autoantibody compared with 13 controls (12%). More women in the endometriosis group had IgG and IgM levels above the normal range. This was statistically significant for IgG in women with grade 3 and for IgM in those with grade 4 endometriosis, IgG levels were significantly higher in antibody-positive women with endometriosis than in the control group. Immunoglobulin and complement component levels tended to have a positive correlation with stage of disease. PMID- 1883793 TI - Maternal plasma corticotrophin-releasing hormone--elevated in preterm labour but unaffected by indomethacin or nylidrin. AB - The role of corticotrophin-releasing hormone (CRH) in preterm labour was studied in 23 women in preterm labour at between 26 and 33 weeks gestation who were randomly allocated to receive treatment with indomethacin (n = 11) or with nylidrin a beta-sympathomimetic agent (n = 12). Maternal plasma CRH in the preterm group (median 70, range 9-597 pmol/l) before therapy was higher (P less than 0.05) than that in 23 control pregnancies, without uterine contractions, matched for gestational age (median 51, range 4-127 pmol/l). CHR levels determined after 3 and 24 h of treatment showed a 10% decrease in the indomethacin group and 10-20% decrease in the nylidrin group, but these changes were not statistically significant. After cessation of uterine contractions during tocolysis, 12 women proceeded to give birth preterm (less than 37 weeks) and their pretreatment CRH levels (median 195, range 9-597 pmol/l) were higher (P less than 0.05) than those in women whose pregnancy proceeded to term (median 52, range 16-207 pmol/l). In another group of women, full-term labour was not accompanied by any changes in maternal CRH levels. Umbilical plasma CRH levels were 1.1-9.8% of the paired maternal levels and did not rise with advancing gestational age. Nor had the type of delivery (elective caesarean section before labour, or preterm or term vaginal delivery) any effect on fetal CRH levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1883794 TI - Prediction of lethal pulmonary hypoplasia and chorioamnionitis by assessment of fetal breathing. AB - Twenty-three pregnancies with fetuses at risk for pulmonary hypoplasia were studied weekly until delivery. The amount of time spent in fetal breathing activity was recorded under controlled conditions during 1 h using real-time ultrasound. An amniotic fluid index was determined. The clinicians and the pathologist were unaware of the ultrasound findings. Eight of 23 fetuses did not breathe at the last ultrasound examination. Three babies died of pulmonary hypoplasia and two of these showed fetal breathing before birth. The three deaths were associated with rupture of the membranes at less than or equal to 20 weeks gestation and of greater than or equal to 44 days duration. One infant developed bronchopulmonary dysplasia. The amniotic fluid index in these four pregnancies was low and the newborn infants had limb contractures. Chorioamnionitis/funisitis was noted in 13 placentas. Eight fetuses were assessed for fetal breathing within 2 days of birth. The lack of fetal breathing had sensitivity, specificity, positive and negative predictive values of 0.75 for chorioamnionitis/funisitis. In this pilot study the absence of fetal breathing was of no value in predicting lethal pulmonary hypoplasia, but was related to chorioamnionitis/funisitis. We recommend further studies of fetal breathing in relation to fetal/neonatal infections. PMID- 1883795 TI - Maternal angiotensin sensitivity and fetal Doppler umbilical artery flow waveforms. AB - The angiotensin pressor response was investigated in normotensive pregnancies which had umbilical Doppler flow velocity waveforms suggestive of placental vascular disease. Of the 36 pregnancies studied at between 24 and 38 weeks gestation, 18 had a positive response to the angiotensin pressor test, these women were delivered earlier (35.3 vs 38.5 weeks, P = 0.015), had a lower mean birthweight centile (14 vs 36, P less than 0.001) and higher frequency of fetal distress in labour (40% vs 7%, P = 0.06) when compared with the 18 women who had a negative response. The Doppler umbilical systolic-diastolic (S-D) ratio decreased with gestation in the negative group, suggesting continuing placental growth and vascular expansion, whereas the S-D ratio increased in the positive group (P less than 0.001), indicative of vascular obliteration. We suggest that the positive angiotensin pressor response is primarily associated with the placental vascular pathology. Angiotensin infusion had no acute effect on maternal uteroplacental or fetal umbilical artery flow velocity waveforms. PMID- 1883796 TI - Vulvar vestibulitis syndrome: a clinico-pathological study. AB - Twenty four patients with the vulvar vestibulitis syndrome formed the basis of this clinicopathological study. Entry dyspareunia was the constant presenting complaint and vestibular erythema with acute superficial tenderness the invariable clinical finding. In our series there was a marked predominance of Caucasians, patients were most often of social classes I and II and most frequently in the third decade. The results of laboratory investigation revealed that this syndrome has a diverse range of potential aetiologies including vulval infections, dysplasia and in one instance acute vasculitis. PMID- 1883797 TI - A comparative study of ethamsylate and mefenamic acid in dysfunctional uterine bleeding. AB - The effects of ethamsylate and mefenamic acid on menstrual blood loss were compared in a double-blind trial in 34 women with menorrhagia. Both drugs produced statistically significant reductions in blood loss during the 3 months of treatment; the overall reduction was 20% in the ethamsylate group and 24% in the mefenamic acid group. Compared with pretreatment values, blood loss was significantly less in each of the 3 treatment months in the mefenamic acid group, but only in the second and third months of treatment in the ethamsylate group. However, more women had a clinically useful reduction in blood loss (greater than 40%) in the ethamsylate group. The onset of effect of mefenamic acid was rapid but ethamsylate showed a comparatively greater effect as the trial progressed. Cessation of treatment was followed by an increase in blood loss, more pronounced in mefenamic acid group who reverted to pre-treatment levels. A greater number of side-effects were reported with mefenamic acid. PMID- 1883798 TI - Quantitative production of prostaglandin E2 and its metabolites by human fetal membranes. AB - Cultured amnion, choriodecidua and intact fetal membrane produced similar quantities of prostaglandin E2 (PGE2) (1-5 ng/ml). Choriodecidua and intact fetal membrane also produced very high levels of PGE2 metabolites (100-1000 ng/ml). The total production of PGE (PGE2 + PGE2 metabolites) was similar in intact fetal membrane and in choriodecidua, suggesting that the amnion, although a source of PGE2, contributes little to the overall PGE production by fetal membranes. PMID- 1883799 TI - The role of postnatal x-ray pelvimetry after caesarean section in the management of subsequent delivery. AB - The purpose of this study was to investigate the influence of postnatal x-ray pelvimetry after caesarean section on the management of the subsequent pregnancy. The case records of 331 women delivered by casearean section in their first pregnancy were reviewed. By standard radiological criteria, the pelvis was considered to be inadequate in 248 (75%) of them and adequate in 83 (25%). Of the women with a radiologically inadequate pelvis, 172 underwent an elective caesarean section. Seventy-six were allowed vaginal delivery: 51 of these women delivered vaginally and 25 required an emergency caesarean section. Of the women with a radiologically adequate pelvis, 61 achieved a vaginal delivery and 22 were delivered by caesarean section. All of the three cases of uterine rupture occurred in women with a radiologically adequate pelvis. This study suggests that x-ray pelvimetry is not a good predictor of the outcome of a trial of vaginal delivery. We conclude that the practice of routine postnatal pelvimetry should be abandoned. PMID- 1883800 TI - Pregnancy after orthotopic liver transplantation. Case report. PMID- 1883801 TI - Congenital afibrinogenaemia and successful pregnancy outcome. Case report. PMID- 1883802 TI - A maternal death caused by AIDS. Case report. PMID- 1883803 TI - Overlap syndrome and its implications in pregnancy. Case report. PMID- 1883804 TI - Cervical preparation with gemeprost for dilatation and evacuation. PMID- 1883805 TI - Early endometrial carcinoma: an incidental finding after endometrial resection. Case report. PMID- 1883806 TI - Use of intra myometrial 15-methyl prostaglandin F2 alpha to control atonic postpartum haemorrhage following vaginal delivery and failure of conventional therapy. PMID- 1883807 TI - Fish-oil and pre-eclampsia. PMID- 1883808 TI - The use of cervicography in a primary screening service. PMID- 1883809 TI - Caveat emptor. PMID- 1883810 TI - Compartmentalized transcription of acetylcholine receptor genes during motor endplate epigenesis. AB - In the adult motor endplate the acetylcholine receptor protein (AChR) is strictly localized under the motor nerve ending, whereas in the noninnervated myotube it is distributed all over the surface of the cell. The genesis of this anisotropic distribution involves a differential regulation of AChR gene transcription. In situ hybridization with AChR subunit probes discloses high levels of unspliced and mature mRNA all over differentiating myotubes. After the entry of the exploratory motor axons, the mRNA clusters located outside the endplate decrease in number and become restricted to the subneural "fundamental" nuclei. Denervation causes a reappearance of unspliced and mature mRNA in extrajunctional areas. A compartmentalized expression of AChR genes take place during endplate formation. Chronic paralysis of the embryo interferes with the disappearance of extrajunctional AChR that, thus, represents an electrical activity-dependent repression of AChR genes. The entry of Ca2+ ions through the sarcolemmal membrane during electrical activity and the activation of protein kinase C plausibly contribute to this membrane-to-gene regulation. The maintenance and late increase in AChR number at the endplate requires the intervention of an anterograde signal or signals, of neural origin. Several factors have been suggested to play a role in this process, such as an acetylcholine receptor-inducing activity (ARIA), ascorbic acid, or calcitonin gene-related peptide (CGRP), a peptide known to coexist with acetylcholine in spinal cord motoneurons. In cultured chick muscle cells, CGRP increases the concentration of surface AChR and alpha-subunit unspliced and mature mRNA and stimulates membrane-bound adenylate cyclase, suggesting that distinct second messengers are involved in the regulation of AChR biosynthesis by electrical activity and by CGRP. The data are interpreted in terms of a model in which it is assumed that (i) in the adult muscle fiber, different stages of gene expression occur in the nuclei in subneural and extrajunctional areas, and (ii) different second messengers elicited by neural factors or electrical activity regulate the state of transcription of these nuclei via trans-acting allosteric proteins binding to cis-acting DNA regulatory elements. The upstream flanking regions of several of the AChR subunit genes reveal ubiquitous DNA elements such as TATA and CAAT boxes, Sp1 binding sites and SV40 core enhancer sites, and muscle-specific MyoD (CANNTG) elements. The contribution of some of these elements to the differential regulation of the multiple AChR subunits is discussed. PMID- 1883811 TI - On the trail of a new regulatory system in plants. Polyomines as modulators of plant development sponsored by Fundacion Juan March, Madrid, Spain, February 4-6, 1991. AB - Investigations into the physiology and biochemistry of polyamines in plants have virtually exploded in the last decade. While not yet accepted by plant physiologists as plant hormones or even as major regulators of plant growth and development, the polyamines require consideration in such varied fields as cell division, organ differentiation, senescence, and stress. We are sure to see more conferences on this subject in the near future. PMID- 1883812 TI - Rapid activation of astrocyte-specific expression of GFAP-lacZ transgene by focal injury. AB - Astrocytes form a key cellular component of the central nervous system. They respond vigorously to diverse neurologic insults by undergoing hypertrophy and increasing expression of the glial fibrillary acidic protein (GFAP) gene, but their functions are largely unknown. To analyze astrocytes in vivo we constructed a transgenic vector from GFAP gene sequences and monitored its efficiency by fusing it to lacZ. Injection of the GFAP-lacZ hybrid gene into the germline of mice yielded six different lines of transgenic mice. In all lines the expression of lacZ was astrocyte-specific. In unmanipulated transgenic animals beta galactosidase activity was much more prominent in astrocytes of the hippocampal formation, selected white matter tracts, and glial limitans than in astrocytes of other areas. This pattern of expression illustrates the physiologic heterogeneity of astrocytes and probably reflects differences in functional demands placed on these cells in different brain regions. Upmodulation of transgene expression was used to determine the time frame within which astroglial activation and increased GFAP gene expression occur following a neurologic insult. Induction of GFAP-lacZ expression was detectable within 1 hour after focal mechanical trauma. This demonstrates that the response of astrocytes to neurologic injury is very rapid and implies that these cells could fulfill important early functions in wound healing within the central nervous system. PMID- 1883813 TI - Experiments on chromosome separation and positioning in Escherichia coli. AB - The way in which sister genomes are spatially separated after replication and positioned in sister cells after division remains unknown for prokaryotes. Experiments with Escherichia coli suggest that individual "chromosomes" (folded, covalently closed circular DNA molecules) are fixed in position within growing cells both before and during replication, but that they are rapidly moved apart by a fixed distance (unit length) immediately after replication has been completed. Such a mitosis-like mechanism accounts for the aberrant positions of DNA and septa in cells in which the normal coordination between DNA replication and cell elongation has been perturbed. PMID- 1883814 TI - A quantitative model for translational control of the GCN4 gene of Saccharomyces cerevisiae. AB - Expression of the GCN4 gene of Saccharomyces cerevisiae is regulated at the translational level by short open reading frames (uORFs) present in the leader sequence of its mRNA. Under conditions of amino acid sufficiency, these sequences restrict the flow of initiating ribosomes to the GCN4 AUG start codon. Mutational analysis of GCN4 has led to a model in which ribosomes must translate the 5' proximal uORF1 and reassemble an initiation complex in order to translate GCN4. This reassembly process is thought to be rapid when amino acids are abundant, such that reinitiation occurs at uORF2, uORF3, or uORF4. Reinitiation at these sites prevents translation of GCN4, presumably because ribosomes dissociate from the mRNA following termination at uORFs 2 to 4. Because of reduced initiation factor activity under starvation conditions, a substantial fraction of ribosomal subunits scanning downstream from uORF1 are not ready to reinitiate when they reach uORFs 2 to 4, but become competent to do so while scanning the additional sequences between uORF4 and GCN4. Examination of the effects of point mutations in the ATG codons of the different uORFs suggests a quantitative model for this control mechanism that describes the probability of reinitiation as a function of the distance scanned downstream from uORF1. This model accounts for the phenotypes of a number of deletion and insertion mutations that alter the intercistronic spacing between the uORFs and GCN4. The correspondence between observed and predicted results implies that the differential rates of reinitiation at GCN4 versus uORFs 2 to 4 are determined largely by the different scanning times required to reach each of these start sites following translation of uORF1. In addition, it supports the notion that an increased scanning-time requirement for reinitiation in amino acid-starved cells forms the basis for translational derepression of GCN4 expression. PMID- 1883815 TI - A single-chain integrin? PMID- 1883816 TI - Antisense inhibition of ras p21 expression that is sensitive to a point mutation. AB - Many genetic disorders result from a single point mutation, and many tumor oncogenes have been found to be altered by a point mutation. The ability to inhibit selectively the expression of the mutated form of a protein without affecting its normal counterpart is central to many therapeutic strategies, since the normal protein may serve indispensable functions. Antisense oligonucleoside methylphosphonates and their psoralen derivatives directed at either normal human Ha-ras p21 or ras p21 that is mutated at a single base in codon 61 have been examined for their efficacy and specificity as inhibitors of p21 expression. Mixed cultures of cells expressing both forms of p21 were treated with the antisense oligomer complementary to the normal p21 or with the antisense oligomer complementary to the point-mutated p21. Each of the antisense oligomers specifically inhibited expression of only the form of ras p21 to which it was completely complementary and left the other form of p21 virtually unaffected. PMID- 1883817 TI - GTP hydrolysis mechanisms in ras p21 and in the ras-GAP complex studied by fluorescence measurements on tryptophan mutants. AB - We have substituted leucine 56 or tyrosine 64 of p21 ras with a tryptophan. The intrinsic fluorescence of this tryptophan was used as an internal conformational probe for time-resolved biochemical studies of the ras protein. The slow intrinsic GTPase, GDP/GTP exchange induced by the SDC25 "exchange factor", and the fast GTP hydrolysis induced by GAP were studied. Tryptophan fluorescence of mutated ras is very sensitive to magnesium binding, GDP/GTP exchange, and GTP hydrolysis (changes in tyrosine fluorescence of wild-type ras are also observed but with a lower sensitivity). Nucleotide affinities, exchange kinetics, and intrinsic GTPase rates of the mutated ras could be measured by this method and were found to be close to those of wild-type ras. The SDC25 gene product enhances GDP/GTP exchange in both mutants. In both mutants, a slow fluorescence change follows the binding of GTP gamma S; its kinetics are close to those of the intrinsic GTPase, suggesting that a slow conformational change precedes the GTPase and is the rate-limiting step, as proposed by Neal et al. (1990) (Proc. Natl. Acad. Sci. U.S.A. 87, 3562-3565). GAP interacts with both mutant ras proteins and accelerates the GTPase of (L56W)ras but not that of (Y64W)ras, suggesting a role for tyrosine 64 in GAP-induced GTP hydrolysis. However, GAP does not accelerate the slow conformational change following GTP gamma S binding in either of the mutated ras proteins. This suggests that the fast GAP-induced catalysis of GTP hydrolysis that is observed with (L56W)ras bypasses the slow conformational change associated with the intrinsic GTPase and therefore might proceed by a different mechanism. PMID- 1883818 TI - Kinetic behavior of the monodehydroascorbate radical studied by pulse radiolysis. AB - The reactions of the monodehydroascorbate radical (As.-) with various biological molecules were investigated by pulse radiolysis. As.- reacted with both fully reduced and semiquinone forms of hepatic NADH-cytochrome b5 reductase with second order rate constants of 4.3 x 10(6) and 3.7 x 10(5) M-1 s-1, respectively, at pH 7.0. In contrast, no reaction of As.- with ferrous cytochrome b5 could be detected by pulse radiolysis, whereas the oxidation of cytochrome b5 by As.- was observed by ascorbate-ascorbate oxidase method. This suggests that the rate constant of As.- with the ferrous cytochrome b5 must be several orders in magnitude smaller than that of the disproportionation of As.-. On the other hand, As.- reduced Fe3+EDTA with a second-order rate constant of 4.0 x 10(6) M-1 s-1 but did not reduce ferric hemoproteins such as metmyoglobin, methemoglobin, and cytochrome b5 by either the pulse radiolysis or the ascorbate-ascorbate oxidase method. PMID- 1883819 TI - Investigation into the source of electron transfer asymmetry in bacterial reaction centers. AB - We have investigated the primary photochemistry of two symmetry-related mutants of Rhodobacter sphaeroides in which the histidine residues associated with the central Mg2+ ions of the two bacteriochlorophylls of the dimeric primary electron donor (His-L173 and His-M202) have been changed to leucine, affording bacteriochlorophyll (BChl)/bacteriopheophytin (BPh) heterodimers. Reaction centers (RCs) from the two mutants, (L)H173L and (M)H202L, have remarkably similar spectral and kinetic properties, although they are quite different from those of wild-type RCs. In both mutants, as in wild-type RCs, electron transfer to BPhL and not to BPhM is observed. These results suggest that asymmetry in the charge distribution of the excited BChl dimer (P*) in wild-type RCs (due to differing contributions of the two opposing intradimer charge-transfer states) contributes only modestly to the directionality of electron transfer. The results also suggest that differential orbital overlap of the two BChls of P with the chromophores on the L and M polypeptides does not contribute substantially to preferential electron transfer to BPhL. PMID- 1883820 TI - Characterization of a female-specific hepatic mitochondrial cytochrome P-450 whose steady-state level is modulated by testosterone. AB - Polyclonal antibody to mitochondrial P-450c27/25 reacted with two proteins of apparent molecular masses of 52 kilodaltons (kDa) and 50 kDa from the female rat liver mitochondrial proteins bound to an omega-octylaminoagarose column. The two proteins were purified to greater than 85% homogeneity by DEAE-Sephacel and hydroxylapatite column chromatography, and both were found to be P-450 as judged by dithionite-reduced CO difference spectra. Both of the P-450 forms required mitochondrial-specific ferredoxin and ferredoxin reductase for in vitro reconstitution of enzyme activities, suggesting that they are mitochondrial forms. The 52-kDa P-450 exhibited the properties of mitochondrial 27/25 hydroxylase with respect to high vitamin D3 25-hydroxylase activity [1.4 nmol (nmol of P-450)-1 min-1] and N-terminal amino acid sequence. The 50-kDa P-450, on the other hand, lacked significant vitamin D3 25-hydroxylase activity, but showed 17 beta-reductase [0.380-0.400 nmol (nmol of P-450)-1 min-1] and 17 beta-oxidase [0.1-0.16 nmol (nmol of P-450)-1 min-1] activities with both androgens and estrogens as substrates. Immunoblot analysis of proteins using a monoclonal antibody specific for P-450c27/25 showed a 2-3-fold higher level of this enzyme in the female liver mitochondria than in the males. Similarly, use of a polyclonal antibody in the immunoblot analysis showed that the 50-kDa P-450 is female-specific. The relative level of P-450c27/25 was reduced significantly in castrated females, while the level of the female-specific 50-kDa P-450 was increased. However, the levels of both enzymes were increased in castrated males.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1883821 TI - Probing the relationship between alpha-helix formation and calcium affinity in troponin C: 1H NMR studies of calcium binding to synthetic and variant site III helix-loop-helix peptides. AB - Three 34-residue peptides corresponding to the high-affinity calcium-binding site III and two variant sequences from the muscle protein troponin C (TnC) were synthesized by solid-phase techniques. The two variant 34-residue peptides had amino acid modifications at either the coordinating positions or both the coordinating and noncoordinating positions, which corresponded to the residues found in the low-affinity calcium-binding site II of TnC. High-field 1H NMR spectroscopy was used to monitor calcium binding to each peptide to determine the effect these amino acid substitutions had on calcium affinity. The dissociation constant of the native site III peptide (SCIII) was 3 x 10(-6) M, smaller than that of the peptide incorporating the ligands from site II (LIIL), 8 x 10(-6) M, and that with the entire site II loop (LII), 3 x 10(-3) M, which bound calcium very weakly. These calcium dissociation constants demonstrate that very minor amino acid substitutions have a significant effect on the dissociation constant and give some insight into why the dissociation constants for site III and IV in TnC are 100-fold smaller than those for sites I and II. The results suggest that the differences in coordinating ligands between sites II and III have very little effect on Ca2+ affinity and that the noncoordinating residues in the site II loop are responsible for the low affinity of site II compared to the high affinity of site III in TnC. PMID- 1883822 TI - 31P NMR saturation-transfer study of the in situ kinetics of the mitochondrial adenine nucleotide translocase. AB - The exchange of intramitochondrial ATP (ATP(in)) for extramitochondrial ATP (ATP(out)) was measured by using 31P NMR spectroscopy over a range of temperatures in isolated rat liver mitochondria oxidizing glutamate and succinate in the presence of external ATP but no added ADP (state 4). The rate of this exchange is more than an order of magnitude faster than rates reported previously that were determined by using isotopic techniques in the presence of oligomycin, the potent ATPase inhibitor. Differences are ascribed in part to the low levels of matrix ATP present in oligomycin-treated mitochondria. The addition of oligomycin to mitochondrial suspensions decreases intramitochondrial ATP levels from 17 +/- 3 (SEM) nmol/mg of protein in state 4 to 1.51 +/- 0.1 nmol/mg of protein in the presence of inhibitor at 8 degrees C. Simultaneously, transporter flux falls from 960 +/- 55 nmol/min.mg to undetectable levels (less than 300 nmol/min.mg). Although transport rates are much faster when measured by saturation-transfer than by conventional isotopic methods, the enthalpy values obtained by determining the effect of temperature on flux are very similar to those reported in the past that were determined by using isotopic techniques. Intramitochondrial ATP content regulates the rate of the ATP(in)/ATP(out) exchange. At 18 degrees C, the concentration of internal ATP that produces half maximal transport rate is 6.6 +/- 0.12 nmol/mg of mitochondrial protein. The relationship between substrate concentration and flux is sigmoidal and is 90% saturated at 11.3 +/- 0.18 nmol/mg of mitochondrial protein.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1883823 TI - Similarities in structure between holocytochrome b5 and apocytochrome b5: NMR studies of the histidine residues. AB - The properties of the six histidine residues of apocytochrome b5 have been investigated by using one- and two-dimensional proton NMR spectroscopy in order to probe the structure remaining after heme removal. Spectral assignments were arrived at by analyzing proton NOE connectivities, comparing them to those observed in the holoprotein, and inspecting the X-ray structure of the latter species. Each histidine residue was studied for its pKa value, interaction with the relaxation agent copper nitrilotriacetic acid, and reactivity toward bromoacetic acid. The four histidines which are not coordinated to the iron atom in the holoprotein (His-15, -26, -27, and -80) display in the major conformer of the apoprotein the same characteristic properties as in the holoprotein. Three of them are involved in specific interactions with the rest of the structure: His-15 and His-80 participate in hydrogen bonds, and His-27 is influenced by the nearby C-terminal segment. His-26 is the most exposed to the solvent. His-63 and His-39, which are located in the heme binding site, have distinct pKa values; they are affected differently by the copper agent and exhibit comparable reactivity toward bromoacetic acid, albeit milder than that of His-26. The results show that the heme binding residues are clearly distinguishable by their physicochemical properties and that several elements of native holoprotein structure are in place in the apoprotein. It is proposed that the structural influence of the heme is localized and that the amino- and carboxy-terminal segments form a structural unit providing stability to the apoprotein and supporting a fluctuating, partially folded binding site. PMID- 1883824 TI - Changes in lipid distribution and dynamics in degranulated rat liver rough endoplasmic reticulum due to the membrane attachment of polyribosomes. AB - Binding of rat liver polyribosomes to homologous degranulated rough endoplasmic reticulum (dRER) labeled with 10-(pyren-1-yl)decanoic acid (PDA) was studied. As a consequence of the membrane association of polysomes, the excimer/monomer fluorescence intensity ratios (Ie/Im) decreased, thus indicating alterations in the dynamics and organization of lipids. These fluorescence changes were complete within approximately 1 min, in accordance with the tight binding of ribosomes to RER. In order to characterize the changes in membrane lipid dynamics in more detail, polysomes were covalently labeled with trinitrobenzenesulfonic acid so as to allow their use as Forster-type resonance energy-transfer acceptors while utilizing PDA as a donor. Accordingly, assuming the binding of native and quencher-labeled ribosomes to the PDA-labeled membranes to be identical, we were able to discriminate fluorescence changes (a) in the proximity of the ribosome binding site from (b) those arising in the surrounding ribosome-free membrane and beyond the effective quenching radii of the TNP residues coupled to polysomes. Our data suggest that lipids in the polysome attachment site of dRER are less mobile than those in the remaining, ribosome-free membrane. In addition, there appears to be a relative enrichment of the PDA probe in the polyribosome membrane attachment sites. PMID- 1883825 TI - Raman spectroscopic studies of model human pulmonary surfactant systems: phospholipid interactions with peptide paradigms for the surfactant protein SP-B. AB - The temperature dependence of dipalmitoylphosphatidylcholine (DPPC)/phosphatidylglycerol (PG) multilayers, reconstituted with various synthetic peptides for modeling human lung surfactant, was monitored by vibrational Raman spectroscopy. The synthetic peptides consisted, respectively, of residues 59-81 of the human surfactant protein SP-B and 21 amino acid residue peptides containing repeating units of arginine separated by either four or eight leucines (RL4 or RL8). Each peptide demonstrated the ability to reduce significantly the surface tension of analogues of the phospholipid mixture used in the Raman studies. Raman spectroscopic integrated band intensities and relative peak height intensity ratios, two spectral parameters used to determine bilayer disorder, provided sensitive probes for characterizing multilayer perturbations in the reconstituted liposomes. Temperature profiles derived from the various Raman intensity parameters for the 3100-2800-cm-1 carbon-hydrogen (C H) stretching mode region, a spectral interval representative of acyl chain vibrations, reflected lipid reorganizations due to the bilayer interactions of these peptides. For the three reconstituted multilamellar surfactant systems, the gel-to-liquid-crystalline phase-transition temperatures Tm, defined by acyl chain C-H stretching mode order/disorder parameters, increased from 35 degrees C in the peptide free system to 37-38 degrees C, indicating increased lipid headgroup constraints for the model liposomes. Although the values of Tm were similar for the three recombinant lipid/peptide assemblies, individual phase-transition cooperativities varied significantly between systems and between spectroscopically derived order/disorder parameters. PMID- 1883826 TI - Postsynthetic methylation of core histones in K562 cells is associated with bulk acetylation but not with transcriptional activity. AB - The relationship between the postsynthetic modification of core histones by methylation and transcriptionally active chromatin was investigated in K562 erythroleukemia cells. Cells were incubated with L-[methyl-3H]methionine in the presence of cycloheximide. Under these conditions, only histones H3 and H4 were detectably methylated. Chromatin was fractionated by several methods, including low-salt elution, mononucleosome gel mobility shift using HPLC-purified HMG 17, and cesium chloride-guanidine equilibrium gradient centrifugation of formaldehyde fixed chromatin. By these latter two methods, chromatin highly enriched for transcriptionally engaged or competent genes was isolated. A significant correlation was noted between postsynthetic modification of histones by methylation and by the slow-turnover form of acetylation. However, there was no enrichment of methylated histones in the transcriptionally competent fraction of chromatin isolated by HMG 17 binding. Moreover, only minor enrichment of methylated histone H3.1 and no enrichment of methylated histones H3.2 and H4 was detected in transcriptionally engaged chromatin isolated by gradient centrifugation. Chromatin soluble in low-salt buffer was found to be significantly enriched in methylated histones, but not in active genes. We conclude that histone methylation is associated with both transcriptionally active and transcriptionally inactive chromatin. The function of this modification, like that of bulk histone acetylation, remains to be determined. PMID- 1883827 TI - Linker DNA bending induced by the core histones of chromatin. AB - We have previously reported that ionic conditions that stabilize the folding of long chromatin into 30-nm filaments cause linker DNA to bend, bringing the two nucleosomes of a dinucleosome into contact [Yao, J., Lowary, P. T., & Widom, J. (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 7603-7607]. Dinucleosomes are studied because they allow the unambiguous detection of linker DNA bending through measurement of their nucleosome-nucleosome distance. Because of the large resistance of DNA to bending, the observed compaction must be facilitated by the histones. We have now tested the role of histone H1 (and its variant, H5) in this process. We find that dinucleosomes from which the H1 and H5 have been removed are able to compact to the same extent as native dinucleosomes; the transition is shifted to higher salt concentrations. We conclude that histone H1 is not essential for compacting the chromatin filament. However, H1 contributes to the free energy of compaction, and so it may select a single, ordered, compact state (the 30-nm filament, in long chromatin) from a family of compact states which are possible in its absence. PMID- 1883828 TI - Expression and characterization of recombinant human acyloxyacyl hydrolase, a leukocyte enzyme that deacylates bacterial lipopolysaccharides. AB - The molecular cloning and eukaryotic cell expression of the complementary DNA for human neutrophil acyloxyacyl hydrolase (AOAH) are described. AOAH is a leukocyte enzyme that selectively removes the secondary (acyloxyacyl-linked) fatty acyl chains from the lipid A region of bacterial lipopolysaccharides (endotoxins), thereby detoxifying the molecules. The two disulfide-linked subunits of the enzyme are encoded by a single mRNA. The amino acid sequence of the protein contains a lipase consensus sequence in the large subunit and a region in the small subunit that is similar to the saposins, cofactors for sphingolipid hydrolases. The recombinant enzyme, like native AOAH, hydrolyzes secondary acyl chains from more than one position on the lipopolysaccharide backbone. Acyloxyacyl hydrolase is a novel two-component lipase that, by deacylating lipopolysaccharides, may modulate host inflammatory responses to Gram-negative bacterial invasion. PMID- 1883829 TI - Purification and biochemical characterization of recombinant simian immunodeficiency virus protease and comparison to human immunodeficiency virus type 1 protease. AB - Simian immunodeficiency virus protease (SIV-PR) was produced in Escherichia coli with a recombinant expression system in which the mature enzyme autoprocessed from a precursor form. Recombinant SIV and HIV-1 (human immunodeficiency virus, type 1) proteases were purified from bacterial cell lysates by use of sequential steps of ammonium sulfate precipitation and size-exclusion and ion-exchange chromatography. The amino acid composition, amino-terminal sequence, and molecular weight (monomer) of the recombinant SIV-PR were in accord with that of the 99 amino acid polypeptide predicted from the SIVMac-PR nucleotide sequence. The active form of SIV-PR was shown to be dimeric by gel filtration chromatography. Inhibition by pepstatin A, time-dependent inactivation by 1,2 epoxy-3-(4-nitrophenoxy)propane, and pH rate profiles using oligopeptide substrates demonstrated that SIV-PR behaves as an aspartic protease. Recombinant HIV-1 Pr55gag precursor was processed in vitro by SIV-PR and HIV-1 PR with indistinguishable proteolytic patterns upon NaDodSO4-polyacrylamide gel electrophoresis. Oligopeptide substrates for HIV-1 PR were found to be suitable substrates for recombinant SIV-PR with the exception of a peptide containing the site identified for p66/p51 cleavage (Phe*Tyr) within HIV-1 reverse transcriptase (RT). Several synthetic peptide analogue inhibitors of HIV-1 PR were also potent inhibitors of SIV-PR, indicating that SIV infection in macaques and rhesus monkeys should be useful models for the preclinical evaluation of acquired immunodeficiency syndrome (AIDS) therapeutics targeted towards the virally encoded HIV-1 protease. PMID- 1883830 TI - Human immunodeficiency virus-1 protease. 1. Initial velocity studies and kinetic characterization of reaction intermediates by 18O isotope exchange. AB - The peptidolytic reaction of HIV-1 protease has been investigated by using four oligopeptide substrates, Ac-Ser-Gln-Asn-Tyr-Pro-Val-Val-NH2, Ac-Arg-Ala-Ser-Gln Asn-Tyr-Pro-Val-Val-NH2, Ac-Ser-Gln-Ser-Tyr-Pro-Val-Val-NH2, and Ac-Arg-Lys-Ile Leu-Phe-Leu-Asp-Gly-NH2, that resemble two cleavage sites found within the naturally occurring polyprotein substrates Pr55gag and Pr160gag-pol. The values for the kinetic parameters V/KEt and V/Et were 0.16-7.5 mM-1 s-1 and 0.24-29 s-1, respectively, at pH 6.0, 0.2 M NaCl, and 37 degrees C. By use of a variety of inorganic salts, it was concluded that the peptidolytic reaction is nonspecifically activated by increasing ionic strength. V/K increased in an apparently parabolic fashion with increasing ionic strength, while V was either increased or decreased slightly. From product inhibition studies, the kinetic mechanism of the protease is either random or ordered uni-bi, depending on the substrate studied. The reverse reaction or a partial reverse reaction (as measured by isotope exchange of the carboxylic product into substrate) was negligible for most of the oligopeptide substrates, but the enzyme catalyzed the formation of Ac-Ser-Gln-Asn-Tyr-Phe-Leu-Asp-Gly-NH2 from the products Ac-Ser-Gln Asn-Tyr and Phe-Leu-Asp-Gly-NH2. The protease-catalyzed exchange of an atom of 18O from H2 18O into the re-formed substrates occurred at a rate which was 0.01 0.12 times that of the forward peptidolytic reaction. The results of these studies are in accord with the formation of a kinetically competent enzyme-bound amide hydrate intermediate, the collapse of which is the rate-limiting chemical step in the reaction pathway. PMID- 1883831 TI - Human immunodeficiency virus-1 protease. 2. Use of pH rate studies and solvent kinetic isotope effects to elucidate details of chemical mechanism. AB - The pH dependence of the peptidolytic reaction of recombinant human immunodeficiency virus type 1 protease has been examined over a pH range of 3-7 for four oligopeptide substrates and two competitive inhibitors. The pK values obtained from the pKis vs pH profiles for the unprotonated and protonated active site aspartyl groups, Asp-25 and Asp-25', in the monoprotonated enzyme form were 3.1 and 5.2, respectively. Profiles of log V/K vs pH for all four substrates were "bell-shaped" in which the pK values for the unprotonated and protonated aspartyl residues were 3.4-3.7 and 5.5-6.5, respectively. Profiles of log V vs pH for these substrates were "wave-shaped" in which V was shifted to a constant lower value upon protonation of a residue of pK = 4.2-5.2. These results indicate that substrates bind only to a form of HIV-1 protease in which one of the two catalytic aspartyl residues is protonated. Solvent kinetic isotope effects were measured over a pH (D) range of 3-7 for two oligopeptide substrates, Ac-Arg-Ala Ser-Gln-Asn-Tyr-Pro-Val-Val-NH2 and Ac-Ser-Gln-Asn-Tyr-Pro-Val-Val-NH2. The pH independent value for DV/K was 1.0 for both substrates, and DV = 1.5-1.7 and 2.2 3.2 at low and high pH (D), respectively. The attentuation of both V and DV at low pH (D) is consistent with a change in rate-limiting step from a chemical one at high pH (D) to one in which a product release step or an enzyme isomerization step becomes partly rate-limiting at low pH (D). Proton inventory data is in accord with the concerted transfer of two protons in the transition state of a rate-limiting chemical step in which the enzyme-bound amide hydrate adduct collapses to form the carboxylic acid and amine products. PMID- 1883832 TI - Stepwise improvements in catalytic effectiveness: independence and interdependence in combinations of point mutations of a sluggish triosephosphate isomerase. AB - Second-site suppressor changes that improve the catalytic potency of a sluggish mutant of the enzyme triosephosphate isomerase have been examined both individually and in combination. Each of the second-site mutations increases the specific catalytic activity of a triosephosphate isomerase in which the catalytic base, glutamate-165, has been changed to aspartate. These second-site suppressors are G10S, S96P, S96T, E97D, V167D, and G233R. Not one of these changes enhances the value of kcat/Km for the wild-type enzyme, which is consistent with the knowledge that the reaction catalyzed by the wild-type enzyme is already diffusion-controlled. Indeed, two of the changes, S96P and V167D, are catalytically deleterious to the wild-type isomerase. When pairs of second-site suppressors are combined with the primary lesion E165D, six pairs show additive independence while the effects of eight other pairs are less than additive. The sites fall into two clusters: pairs within a cluster always interfere with one another and do not produce additive improvements in catalytic activity, whereas combinations of changes from different clusters tend to be additive in their effects. No combination of second-site suppressor mutations behaves synergistically, though there seems to be no a priori reason to exclude this possibility. Since the catalytic potency of each of the six second-site suppressor mutants can be further improved by the introduction of (at least) one of the other five changes, it is evident that none of the double mutants lies at a local catalytic maximum. In these cases, therefore, the opportunity exists for at least two "steps" of monotonic catalytic improvement along each of six different "paths" in protein space. PMID- 1883833 TI - Mapping the active site of meprin-A with peptide substrates and inhibitors. AB - The extended substrate-binding site of meprin-A, a tetrameric metalloendopeptidase from brush border membranes of mouse kidney proximal tubules, was mapped with a series of peptide substrates. Previous studies led to the development of the chromogenic substrate Phe5(4-nitro)bradykinin for meprin A. With this substrate, several biologically active peptides were screened as alternate substrate inhibitors, and, of these, bradykinin (RPPGFSPFR) was found to be the best substrate with a single cleavage site (Phe5-Ser6). Three types of bradykinin analogues were used for a systematic investigation of substrate specificity: (1) nonchromogenic bradykinin analogues with substitutions in the P3 to P3' subsites were used as alternative substrate inhibitors of nitrobradykinin hydrolysis, (2) analogues of nitrobradykinin with variations in the P1' position were tested as substrates, and (3) intramolecularly quenched fluorogenic bradykinin analogues with substitutions in the P1 to P3 sites were tested as substrates. A wide variety of substitutions in P1' had little effect on KM (174 339 microM) but markedly affected kcat (51.5 s-1 = A greater than S greater than R greater than F greater than K greater than T greater than E = 0). Substitutions in P1 had a greater effect on KM (366 microM-2.46 mM) and also strongly affected kcat (98.5 s-1 = A greater than F much greater than L greater than E greater than K = 2.4 s-1). The variety of allowed cleavages indicates that meprin-A does not have strict requirements for residues adjacent to the cleavage site. Substitutions farther from the scissle bond also affected binding and hydrolysis, demonstrating that multiple subsite interactions are involved in meprin-A action.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1883834 TI - The regulation and nature of the cyanide-resistant alternative oxidase of plant mitochondria. AB - In addition to possessing multiple NAD(P)H dehydrogenases, most plant mitochondria contain a cyanide- and antimycin-insensitive alternative terminal oxidase. Although the general characteristics of this terminal oxidase have been known for a considerable number of years, the mechanism by which it is regulated is unclear and until recently there has been relatively little information on its exact nature. In the past 5 years, however, the application of molecular and novel voltametric techniques has advanced our understanding of this oxidase considerably. In this article, we review briefly current understanding on the structure and function of the multiple NADH dehydrogenases and consider, in detail, the nature and regulation of the alternative oxidase. We derive a kinetic model for electron transfer through the ubiquinone pool based on a proposed model for the reduction of the oxidase by quinol and show how this can account for deviations from Q-pool behaviour. We review information on the attempts to isolate and characterise the oxidase and finally consider the molecular aspects of the expression of the alternative oxidase. PMID- 1883835 TI - Characterization of genes that encode subunits of cucumber PS I complex by N terminal sequencing. AB - N-terminal amino acid sequencing was carried out to characterize the genes of the cucumber PS I complex (PSI-100) that contains eight polypeptides and catalyzes the light-dependent transfer of electrons from plastocyanin to ferredoxin. The genes of all subunits except the 17.5 kDa polypeptide in PSI-100 have been identified. These are psaA/psaB (65/63 kDa), psaD (20 kDa), psaE (19.5 kDa), psaF (18.5 kDa), psaH (7.6 kDa), and psaC (5.8 kDa). The 17.5 kDa polypeptide is a new protein and is designated tentatively as the gene product of psaM. N-terminal amino-acid sequencing indicated the presence of two polypeptides in the 7.6 kDa band. One of these is the gene product of psaH and is essential for the activity of the PS I complex, and the other one is as yet unrecognized and largely depleted in the PSI-100 complex. Gene products of psaG, psaI, and psaK, which have been proposed as the components of PS I complex, are not involved in the PSI 100 complex, but are involved in the PS I complex (PSI-200), which contains 120 chlorophyll per reaction center chlorophyll (P700) and light-harvesting chlorophyll a/b protein complexes. Three polypeptides (26,23 and 22.5 kDa) are not involved in the PSI-100 and are assigned as the apo-protein of light harvesting chlorophyll a/b protein complexes. PMID- 1883836 TI - Molecular cloning of cDNA for antimycin A-inducible mRNA and its role in cyanide resistant respiration in Hansenula anomala. AB - A cDNA for mRNA induced by antimycin A in Hansenula anomala was cloned. The mRNA for the cDNA was expressed in the yeast under the conditions expressing the cyanide-resistant respiration activity. The nucleotide sequence revealed a long open reading frame of 342 codons encoding a protein with a molecular weight of 40,282 in the cDNA. An antibody recognizing the protein encoded by the open reading frame was produced. Immunoblotting of H. anomala proteins with this antibody showed that a 36 kDa protein localized in mitochondria was a mature form of the protein encoded by the cDNA. It is suggested that the cloned cDNA encodes a protein involved in the cyanide-resistant respiratory pathway. PMID- 1883837 TI - An adult male specific gene in Drosophila containing the repetitive element opa. AB - A cDNA has been isolated for an adult male specific gene in Drosophila that contains the repetitive element opa. We have named this gene Dromsopa for Drosophila male specific opa containing gene. The 0.6 kb mRNA for this gene is only found in the abdominal region of adult male Drosophila and in no other tissue or at other developmental stages. The Dromsopa opa repeat codes for the usual stretch of poly(glutamine) interrupted by histidine residues. The opa repetitive element was originally found in the Drosophila Notch gene (Kidd, S. et al. (1983) Cell 34, 431-433 and Wharton, K.A. (1985) Cell 40, 55-62) and has, more recently, been found in genes under developmental or tissue specific control from yeast to humans. The gene was cloned using a genomic fragment during a chromosomal walk upstream of the AP3 gene located at chromosomal location 79CD on the left arm of the third chromosome (Kelley, M.R. et al. (1989) Mol. Cell. Biol. 9, 965-973). The Dromsopa gene has no other identity with genes currently in the databases, once the opa repeat is excluded. The possibility that the Dromsopa gene is a male specific regulatory factor is under investigation as is its precise location within the abdomen, such as in germ line tissue. PMID- 1883838 TI - Cloning and nucleotide sequence of cDNA encoding human erythrocyte band 7 integral membrane protein. AB - cDNA clones encoding the human erythrocyte band 7 membrane protein were isolated by immunoscreening from bone marrow and HeLa cell lambda gt 11 cDNA libraries, and their nucleotide sequences were determined. HeLa- and bone marrow cell derived sequences were identical, except for one nucleotide; the deduced sequence of 287 amino acids was confirmed by sequence identity with peptides of the erythroid protein. Structure analysis assigned band 7 protein to the type Ib transmembrane proteins. PMID- 1883839 TI - Complete nucleotide sequences of major plasma protein genes of Bombyx mori. AB - In the silkworm, Bombyx mori, a family of hormone-sensitive genes encodes major plasma proteins, termed '30K proteins'. We reported the organization of the 30K protein gene family together with the structure and expression of a member of the gene family (Mori, S. et al. (1991) J. Mol. Biol. 218, 7-12). In this communication, we present the complete structures of two other 30K protein genes in the family. Sequence analyses demonstrated that all three genes are similar to each other; a short first exon and protein-coding second exon are interspersed by a single intron. Structures homologous to the putative regulatory elements for the 30K protein gene expression are also found around each gene. PMID- 1883840 TI - Nucleotide sequence analysis of the CT operon of the Vibrio cholerae classical strain 569B. AB - The complete nucleotide sequence of the Vibrio cholerae classical strain 569B was determined. The results prove the exactness of the amino acid CT B sequence published by Takao et al. (1985, Eur. J. Biochem. 146, 503-508). A comparison is made with already reported CT genes. PMID- 1883841 TI - Complex regulation of tumor necrosis factor mRNA turnover in lipopolysaccharide activated macrophages. AB - The turnover of tumor necrosis factor (TNF) mRNA in permanently transfected macrophages of the RAW 264.7 cell line was studied directly (by Northern blot analysis using a probe specific for TNF) and indirectly (through studies of the turnover of various reporter mRNAs, either containing or lacking the TNF 3' untranslated region (UTR)). The TNF mRNA was found to be very unstable in RAW 264.7 cells. Instability appeared to result from two distinguishable nucleolytic processes. The major degradative process involved was not specific for the TNF 3' UTR of reporter mRNAs, and was inhibited by actinomycin D pretreatment. It appeared to be expressed constitutively, in that cell activation by lipopolysaccharide (LPS) did not modify message stability. When cells were treated with actinomycin D, a minor nucleolytic activity was 'uncovered'. This minor activity was noted to increase with time following LPS activation. It also exhibited specificity, in that reporter mRNAs bearing the 3' UTR of TNF were more susceptible to degradation in the presence of actinomycin D than were constructs lacking the 3' UTR of TNF. Thus, TNF mRNA turnover appears complex, and depends upon at least two separable degradative pathways. The TNF 3' UTR apparently contributes only modestly to the instability of this mRNA under normal conditions. PMID- 1883842 TI - Histones and DNA methylation in mammalian chromatin. Differential inhibition by histone H1. AB - Histones (from calf thymus or from human placenta), if renatured in the presence of EDTA, caused a severe inhibition of in vitro methylation of double-stranded DNA (from Micrococcus luteus) by human placenta DNA methyltransferase. The absence of EDTA during the histone renaturation procedure abolished--at least in the 'physiological' range of the histones/DNA ratio--the inhibition. The H1 component was responsible for this inhibition, no effect being exerted by the other histones. H1 preparations were more effective if renatured in the presence of EDTA--90% inhibition being reached at a 0.3:1 (w/w) H1/DNA ratio. It seems likely that the requirement for the presence of EDTA during the renaturation process is correlated to its ability to induce a fairly stable ordered conformation of the histones, although this effect could also be shown with the 'inactive' H2a, H2b and H3 components, and was instead less evident with histone H1. The restriction to histone H1 of the ability to inhibit enzymic DNA methylation may account for the lower methylation levels present in the internucleosomal DNA of mammalian chromatin. PMID- 1883843 TI - Enhancement of DNA replication by transcription factors NFI and NFIII/Oct-1 depends critically on the positions of their binding sites in the adenovirus origin of replication. AB - The origin of DNA replication of many human adenoviruses is composed of a highly conserved core origin and an auxiliary region, containing the binding sites for NFI and NFIII/Oct-1. We examined enhancement of DNA replication in vitro by the purified functional DNA-binding domains of NFI (NFI-BD) and NFIII/Oct-1 (the POU domain), using origins in which the positions of the binding sites for these proteins were transposed. Insertion or deletion of two or three base pairs between the core origin and the NFI binding site resulted in a 3-5-fold decrease of stimulation, whereas larger insertions gradually reduced the stimulation further. Mutants in which the NFI binding site was separated approximately one or two helical turns from the core origin by AT-rich sequences could still be stimulated by NFI. In contrast, insertion of two or more base pairs between the NFI and NFIII/Oct-1 binding sites abolished stimulation by NFIII/Oct-1 almost completely. Furthermore, stimulation by this protein was lost when the Ad2 NFIII/Oct-1 binding site was transposed to a position closer to the core origin, destroying the NFI binding site. This shows that the position of the NFIII/Oct-1 binding site is essential for stimulation. Models to explain these position dependent effects on stimulation are discussed. PMID- 1883844 TI - Expression and characterization of recombinant human ciliary neurotrophic factor from Escherichia coli. AB - The gene for ciliary neurotrophic factor (CNTF) was cloned from a human genomic DNA library by screening with a DNA fragment amplified from human genomic DNA using the polymerase chain reaction. A DNA sequence coding for human CNTF was placed under control of an regulatable promoter in the expression vector pJU1003 and transformed into Escherichia coli strain BL21(DE3). Induction of expression in cultures of this transformant led to the accumulation of approx. 25 mg/l per A600 unit of human CNTF. CNTF was purified to homogeneity from cell lysates via anion-exchange, cation-exchange and Zn(2+)-affinity chromatography. Purified CNTF contained less than 0.1% contaminating E. coli proteins, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), Western blot analysis and reversed-phase high-pressure liquid chromatography (HPLC). The protein exhibited an ultraviolet absorption maximum at 279 nm with a calculated extinction coefficient of A1%(279) = 9.0. Peptide map and amino acid sequence analyses confirmed that the expressed protein has the amino acid sequence expected for human CNTF, except for the absence of the amino-terminal methionine. High-purified recombinant human CNTF supported the survival of chick embryo parasympathetic, sympathetic and sensory neurons in culture at low picomolar concentrations. These results indicate that the biological activities previously ascribed to impure CNTF preparations indeed reside in one molecule. PMID- 1883845 TI - Mammalian mRNAs encoding protein closely related to ubiquitin-conjugating enzyme encoded by yeast DNA repair gene RAD6. AB - A clone of about 1 kb has been isolated from a human brain cDNA library. The clone possesses a 151 amino acid open reading frame that exhibits 72% amino acid identity with the E2 ubiquitin-conjugating enzyme encoded by the RAD6 gene of Saccharomyces cerevisiae. A 90% amino acid identity was observed in a central sequence surrounding a cysteine, which most likely contributes the sulfhydryl group involved in the formation of the ubiquitin-E2 thiolester linkage. Northern hybridization analyses have identified a poly(A)-containing mRNA of about 1 kb encoding the E2-like sequence in human CEM lymphoblastoid and HeLa cells, Novikoff rat hepatoma cells and S49 mouse leukemia cells. Southern hybridization analyses indicate the presence of a single gene encoding this sequence in both human cell lines, but of two or more related genes in the rodent cell lines. PMID- 1883846 TI - Hepatic and renal expression of rat apolipoprotein E under control of the metallothionein promoter in transgenic mice. AB - We created three lines of transgenic mice with an integrated rat genomic apolipoprotein E gene fused with the mouse metallothionein I promoter. These lines transcribed rat apoE mRNA in the liver and/or in the kidney and expressed significant amounts of rat apoE in plasma. Enhancement of the plasma level by treatment with Zn ion or Bi ion was observed. PMID- 1883847 TI - Induction of differentiation of human myeloid leukemia HL-60 cells by novel pyrimidine nucleoside analogs. AB - New pyrimidine nucleoside analogs (18 compounds) were synthesized and their growth-inhibiting and differentiation-inducing activities on human myeloid leukemia HL-60 cells were examined. Some of the analogs were found to induce nitroblue tetrazolium (NBT) reducing activity in the HL-60 cells. The inducing activities of these compounds were compared at their concentrations for 50% inhibition of cell growth. TI-79 (3-benzyl-5-methyl-3-(beta-D ribofuranosyl)pyrido[2,3-d]pyrimidine- 2,4(1H,3H)-dione) was a very effective inducer of NBT-reduction and of differentiation of the cells into mature granulocytes. The induction of NBT-reducing activity by TI-79 was inhibited by high concentrations of the natural nucleoside, adenosine. Other differentiation inducers, such as retinoic acid, 1 alpha,25-dihydroxyvitamin D-3 and staurosporin markedly enhanced the induction of differentiation of HL-60 cells by TI-79. Nucleoside analogs such as TI-79 should be useful for differentiation therapy of some types of myelogenous leukemia. PMID- 1883848 TI - Effects of steroidal and non-steroidal antiandrogens on the androgen binding properties of the rat ventral prostate androgen receptor. AB - Steroidal (cyproterone acetate) and non-steroidal (RU23908 and hydroxyflutamide) antiandrogens are able to block testosterone-induced increases in nuclear androgen receptor (AR) in the prostate of 1-day orchidectomized rats, but when given alone, RU23908 and hydroxyflutamide increase nuclear AR (RU23908 greater than hydroxyflutamide) in the same animal model. The increases in nuclear AR induced by antiandrogen alone or with testosterone alone are blocked by cycloheximide 1 h after administration, suggesting that androgen or antiandrogens induce de novo AR synthesis. Concomitant to nuclear AR accumulation, testosterone is able to induce depletion of cytosol and microsomal AR. Blockade of testosterone-induced depletion of microsomal AR, but not of cytosol AR, occurs in the presence of antiandrogens. Cyproterone acetate has a higher relative binding affinity (RBA) for microsomal AR and cytosol AR than RU23908 or hydroxyflutamide. This phenomenon is in good agreement with the degree of inhibition by these compounds of the association rate of androgen for the microsomal AR. This correlation between RBA and inhibition of the initial rate of hormone binding to the receptor is not found for cytosol AR. The results show that antiandrogens are not 'pure' antagonists of androgen action and they are potent agonists in the absence of testosterone. Furthermore, testosterone alone or antiandrogens per se regulate AR levels acutely by protein-synthesis dependent mechanisms of action, in rat ventral prostate. PMID- 1883849 TI - Determination of endogenous levels of cyclic ADP-ribose in rat tissues. AB - Cyclic ADP-ribose (cADPR) is a potent mediator of calcium mobilization in sea urchin eggs. The cADPR synthesizing enzyme is present not only in the eggs but also in various mammalian tissue extracts. The purpose of this study was to ascertain whether cADPR is a naturally occurring nucleotide in mammalian tissues. Rat tissues were frozen and powdered in liquid N2, followed by extraction with perchloric acid at -10 degrees C. [32P]cADPR was prepared and used as a tracer. The acid extracts were chromatographed on a Mono-Q column and cADPR in the fractions were determined by its ability to release Ca2+ from egg homogenates. That the release was mediated by cADPR and not inositol trisphosphate (IP3) in the extracts was shown by the fact that the homogenates, subsequent to Ca2+ release induced by active fractions, were desensitized to authentic cADPR but not to IP3. Furthermore, the Ca2+ release activity was shown to co-elute with [32P]cADPR. The endogenous level of cADPR determined in rat liver is 3.37 +/- 0.64 pmol/mg, in heart is 1.04 +/- 0.08 pmol/mg and in brain is 2.75 +/- 0.35 pmol/mg. These results indicate cADPR is a naturally occurring nucleotide and suggest that it may be a general second messenger for mobilizing intracellular Ca2+. PMID- 1883850 TI - The antioxidant butylated hydroxytoluene stimulates platelet protein kinase C and inhibits subsequent protein phosphorylation induced by thrombin. AB - The phenolic antioxidant 2,6-bis(1,1-dimethyl ethyl)-4-methylphenol (BHT) evokes a transient phosphorylation of two platelet proteins of Mr 20,000 and 47,000 that are well-known substrates of protein kinase C (PKC) and, similarly to phorbol esters, a slight but persistent phosphorylation of a protein of Mr 26,000. These effects are observed both in the presence and in the absence of extracellular calcium, but are abolished in the presence of the protein kinase C inhibitor staurosporine. The phosphorylation of the 47 kDa protein takes place mostly at the serine and, to a lesser extent, at threonine residues. BHT induces an increased binding of tritiated phorbol dibutyrate to platelets indicating a PKC translocation from cytosol to plasma membrane. Addition of BHT (20 microM) a few min prior to thrombin causes inhibition of both agonist-evoked protein phosphorylation and increase in the Ca2+ concentration, the latter inhibition being counteracted by staurosporine. The inhibitory effect lasts for several minutes even after removal of BHT from the cellular suspending medium. Similar results are obtained with nordihydroguaiaretic acid, whereas 2- and 3-tert-butyl 4-methoxyphenol (BHA) produce only slight effects. BHT activates the protein kinase C purified from pig brain in a concentration-dependent manner (up to 200 microM), whereas it does not affect the activity of other purified protein kinases such as type 1 and 2 casein kinases, type II A, II B and III tyrosine protein kinases from rat spleen and the catalytic subunit of cyclic AMP-dependent protein kinase. It is concluded that, similarly to diacylglycerols and phorbol esters, these phenolic antioxidants activate the protein kinase C, which in turn desensitizes platelets towards subsequent phospholipase C activation. PMID- 1883851 TI - Corticosteroid effects on lipid lateral diffusion in CEM-C1 and CEM-C7 acute lymphoblastic leukemia cells. AB - We have examined glucocorticoid effects on CEM-C7 and CEM-C1 subclones of a leukemic human T-cell line using fluorescence photobleaching recovery techniques. Incubation with 10(-5) M triamcinolone acetonide (TA) increased lipid lateral diffusion on steroid-sensitive CEM-C7 cells but had no effect on steroid resistant CEM-C1 cells. CEM-C7 cells incubated in serum-free medium responded only to TA but, when fetal calf serum was added to the incubation medium, would also respond to 10(-5) M dexamethasone and hydrocortisone. Thus, glucocorticoids can cause increased lipid lateral diffusion in CEM-C7 cells, while having no effect on steroid-resistant CEM-C1 cells. PMID- 1883852 TI - Effects of azumolene on doxorubicin-induced Ca2+ release from skeletal and cardiac muscle sarcoplasmic reticulum. AB - The mechanism of doxorubicin-induced Ca2+ release from skeletal and cardiac muscle sarcoplasmic reticulum (SR) was studied by examining the effects of azumolene (a water soluble dantrolene analog) on doxorubicin-mediated Ca2+ release and ryanodine binding. Doxorubicin induced a rapid Ca2+ release from both skeletal and cardiac SR in a similar concentration range (EC50 = 5-10 microM). Maximal doxorubicin-induced Ca2+ release was seen at 2 and 0.2 microM Ca2+ for skeletal and cardiac SR, respectively. Addition of 400 microM azumolene caused approx. 30% inhibition of doxorubicin-induced Ca2+ release from both skeletal and cardiac SR; skeletal SR had significantly higher sensitivity to azumolene than cardiac SR. In the presence of Ca2+, doxorubicin increased [3H]ryanodine binding to both skeletal and cardiac SR; whereas in the absence of Ca2+, doxorubicin led to significant ryanodine binding to skeletal SR, but not to cardiac SR. In both types of SR, doxorubicin-activated, but not Ca2+ activated ryanodine binding was inhibited by azumolene. Azumolene sensitivity for inhibition of doxorubicin activated ryanodine binding was much higher in skeletal SR than cardiac SR, consistent with the results for effects of azumolene on Ca2+ release. Our results are consistent with the possibility that azumolene inhibits doxorubicin binding by direct competition for the drug receptor(s). PMID- 1883853 TI - Relationship between total magnesium concentration and free intracellular magnesium in sheep red blood cells. AB - The cellular free magnesium concentration of ionophore A23187 permeabilized high potassium sheep erythrocytes was measured by 31P nuclear magnetic resonance spectroscopy, and the total cellular magnesium concentration was determined by atomic absorption spectroscopy. The free versus total cellular magnesium concentrations yield a linear relationship on a log-log scale in the concentration range from 0.3 to 1.92 mmol Mg/liter cells. Thus, free intracellular magnesium concentrations can be calculated from atomic absorption data. The method permits the estimation of physiologically or experimentally induced variations of intracellular free magnesium concentrations between 7 and 405 microM magnesium in cell water. This range encompasses the free magnesium concentration of 335 +/- 60 microM in cell water determined for untreated erythrocytes. PMID- 1883854 TI - Phorbol ester, prolactin, and relaxin cause translocation of protein kinase C from cytosol to membranes in human endometrial cells. AB - Incubation of endometrial cells with 100 nM 12-O-tetradecanoylphorbol 13-acetate (TPA) for 2, 5, 10 and 30 min decreased cytosolic protein kinase C (PKC) activity to 80%, 68%, 66%, and 72% of the control values, while membrane-associated PKC increased to 116%, 168%, 154% and 134% of the control values, respectively. Long term incubation of cells with TPA resulted in a loss in total PKC activity. Treatment of secretory endometrial cells with prolactin (100 ng/ml) decreased cytosolic PKC to 64% (10 min) and 72% (20 min) while membrane PKC increased to 133% (10 min) and 158% (20 min) compared to control values. Relaxin (100 ng/ml) also caused translocation of PKC in secretory endometrium. Neither hormone induced PKC translocation in proliferative endometrium. In intact endometrial cells TPA stimulated the phosphorylation of an 80 kDa protein. Cytosolic protein phosphorylation in the presence of EGTA resulted in phosphorylation of proteins of 68 kDa and 19 kDa which was increased by prolactin. Upon activation by calcium and phosphatidylserine, PKC phosphorylated a protein of 39 kDa, and prolactin did not further enhance its phosphorylation. The present results indicate that TPA induces an intracellular translocation and down-regulation of PKC. The translocation of PKC by prolactin and relaxin suggests an involvement of this enzyme in the action of these hormones in human endometrium. PMID- 1883855 TI - Insulin and phorbol ester stimulate phosphorylation of a 15,000 dalton membrane protein in rat diaphragm in a similar manner. AB - The effects of insulin on the phosphorylation of a 15 kilodalton (kDa) membrane protein in rat diaphragm in situ have been investigated. Incubation of the diaphragm with insulin or tumor-promoting phorbol ester increased the 32P labelling of the 15 kDa protein at serine residues by 50 +/- 8% and 64 +/- 11%, (mean +/- S.E.), respectively. Thermolytic peptide mapping of the 15 kDa protein after insulin treatment of the diaphragm yielded two major phosphopeptides, one of which was absent from digests from control diaphragms. The same two phosphopeptides were identified after incubation of the diaphragm with phorbol ester and after phosphorylation of sarcolemma in vitro with [gamma-32P]ATP and protein kinase C. Additional experiments indicated that pretreatment of diaphragms with insulin or phorbol ester both increased the state of phosphorylation of the 15 kDa sarcolemma protein on phosphorylation sites regulated by protein kinase C. The stimulatory effect of insulin was decreased by staurosporine or by preincubation of the diaphragms with phorbol esters. These results indicate that the insulin-induced increases in protein kinase C activity previously found in rat diaphragm (Walaas et al. (1987) FEBS Lett. 220, 311-318) may be involved in insulin-mediated regulation of phosphorylation of the 15 kDa protein in situ. PMID- 1883856 TI - Application of FRIT fast atom bombardment liquid chromatography/mass spectrometry for the determination of acetylcholine levels in rat brain regions. AB - This report describes the use of FRIT fast atom bombardment (FAB) liquid chromatography/mass spectrometry for the analysis of acetylcholine in rat brain regions. Direct assessment of acetylcholine levels is possible without the need for either derivatization or extensive sample preparation. Quantification is accomplished by monitoring intact molecular cations of acetylcholine and a deuterated internal standard. The results are compared with those obtained by conventional pyrolysis gas chromatography/mass spectrometry and by liquid chromatography with electrochemical detection. PMID- 1883857 TI - Determination of CGS 16617 and stable isotope-labeled CGS 16617, an angiotensin converting enzyme inhibitor, in human plasma by gas chromatography/mass spectrometry. AB - An analytical method has been developed for the simultaneous determination of a novel orally active angiotensin-converting enzyme inhibitor (CGS 16617) and a stable isotope-labeled analog. Both compounds are isolated from human plasma using an ion-exchange column, derivatized with pentafluoropropionic anhydride and pentafluoropropanol, and analyzed by gas chromatography/mass spectrometry. After splitless injection on a methyl-silicon column, the compound is detected using negative ion chemical ionization with nitrous oxide as a reagent gas. CGS 16617 labeled with four deuteriums and two 13C is used as an internal standard. The accuracy and precision of the method, expressed as the overall mean +/- SD recovery obtained from two sets of 36 quality-control samples used during a clinical study (concentration range 0.2-100 ng ml-1 plasma), was 96.1 +/- 16.2% for unlabeled drug and 97.6 +/- 14.4% for the D4-labeled drug (concentration range 0.2-100 ng ml-1 plasma). The limit of quantification using 1 ml plasma is 0.2 ng ml-1 for both labeled and unlabeled drug. PMID- 1883858 TI - Assay of mevalonate in plasma. PMID- 1883859 TI - GC/MS/MS detection of detomidine carboxylic acid in horse urine. PMID- 1883860 TI - Characterization of lipoxins by combined gas chromatography and electron-capture negative ion chemical ionization mass spectrometry: formation of lipoxin A4 by stimulated human whole blood. AB - The lipoxins are a recent addition to the family of bioactive products derived from arachidonic acid. Here, we have prepared pentafluorobenzyl ester, trimethylsilyl ether derivatives of lipoxin A4, lipoxin B4 and pentadeuterolipoxin A4 and have characterized these products by electron-capture negative ion chemical ionization gas chromatography/mass spectrometry (NICI GC/MS). Lipoxin A4 (5S,6R,15S-trihydroxy-7,9,13-trans-11-cis-eicosa-tetraenoic acid; LXA4) was quantified following extraction from whole blood by stable isotopic dilution utilizing deuterium-labeled LXA4 as internal standard and selected ion monitoring of the [M--pentafluorobenzyl] anions. Studies with a second tritiated internal standard (e.g. [11,12-3H]LXA4) also showed that the recovery of LXA4 was greater than 80% following solid-phase extraction from whole blood, and greater than 90% from isolated cells. In addition, neither isolated neutrophils nor platelets oxidatively metabolized [11,12-3H]LXA4 when incubated in the presence or absence of stimuli. Whole blood incubated with either the ionophore of divalent cations (A23187), thrombin, or thrombin plus the chemotactic peptide formylmethionyl-leucine-phenylalanine generated both LXA4 and thromboxane, which were quantified by stable isotope dilution. The ratio of thromboxane to LXA4 formed by stimulated whole blood ranged from approximately 2:1 to 20:1. These results indicate that the lipoxins display suitable characteristics as their respective pentafluorobenzyl ester, trimethylsilyl ether derivatives for quantification by electron-capture NICI GC/MS. Moreover, they provide evidence that LXA4 can be generated from endogenous sources in whole blood following exposure to physiologically relevant stimuli. PMID- 1883861 TI - Lipids from the guinea pig Harderian gland: use of picolinyl and other pyridine containing derivatives to investigate the structures of novel branched-chain fatty acids and glycerol ethers. AB - The lipid extracted from guinea pig Harderian glands was hydrolysed and the constituents were examined as trimethylsilyl (TMS), (2H9)TMS, methyl ester/TMS, acetonide/TMS, nicotinate/TMS, picolinyl/TMS and nicotinylidene/TMS derivatives by capillary gas-liquid chromatography and gas chromatography/mass spectrometry. Over 70 compounds amounting to over 93% of the extract were identified. These consisted of 1-O-alkyl glycerols (glycerol ethers) with alkyl chains containing from 17 to 21 carbon atoms and fatty acids ranging from 14 to 26 carbon atoms. The alkyl chains in the glycerol ethers were straight, mono- and dimethyl branched with the major site of branching being at C-14. All straight-chain acids from C14 to C26 were present, with the most abundant being n-24:0. Again mono- and dimethyl branched structures comprised the bulk of the remaining acids. Methyl groups tended to be towards the middle of the chain rather than in the more usual omega-1 (iso) and omega-2 (anteiso) positions, with C-14 again being a major site. The shorter-chain acids tended to have methyl groups closer to the acid group, with several of the short-chain compounds being substituted at C-2. Structural information on the acids was provided by the picolinyl derivatives and the sample provided an opportunity to evaluate these derivatives with branched acids other than the iso and anteiso compounds studied previously. They were found to be satisfactory for analysis of both mono- and dimethyl branched acids with the possible exception of compounds containing a methyl branch at C-4. However, in this case, structural information was provided by the methyl ester.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1883862 TI - Study of reactions induced by hydroxylamine treatment of esters of organic acids and of 3-ketoacids: application to the study of urines from patients under valproate therapy. AB - Hydroxylamine used at alkaline pH as oximating agent in the search for organic aciduria by gas chromatography/mass spectrometry (GC/MS) induces other chemical reactions. Esters are partially transformed in their corresponding hydroxamic acids. GC/MS characteristics of the trimethylsilylated derivatives of the hydroxamic acids arising from alpha-unsaturated esters are here reported. Their mass spectral fragmentation helps in the recognition of peaks arising from the glucuronides of 2-ene- and probably 2,3'-diene-valproic acid. By heating in the injection port of the gas chromatograph, part of some trimethylsilylated hydroxamic acids are transformed to the corresponding isocyanates by a Lossen like rearrangement. In addition to the corresponding hydroxamic acids, hydroxylamine treatment of alpha-unsaturated esters forms 2-isoxazolidin-3-ones by intramolecular Michael addition. GC/MS characteristics of the trimethylsilylated derivatives of these compounds are reported. Submitted to hydroxylamine, 3-ketoacids forms 2-isoxazolin-5-ones by cyclization of the oximes after acidification. This explains the existence of two GC peaks observed from urine extracts of patients under valproate therapy, which correspond to two tautomers of 2-isoxazolin-5-one originating from the oximes of the 3-keto valproic acid. PMID- 1883863 TI - Nicotinylidene derivatives for the structural elucidation of glycerol mono-ethers and mono-esters by gas chromatography/mass spectrometry. AB - Nicotinylidene and methylnicotinylidene derivatives of representative glycerol ethers and glycerol esters were prepared by their reaction with pyridine-3 carboxaldehyde and 3-acetyl pyridine respectively. Each compound gave two sets of diastereoisomers which could be separated by gas-liquid chromatography. The extent of formation of the derivatives was nearly quantitative and chromatographic peak shape was good. The compounds producing both peaks gave similar spectra but with differences that were characteristic of the isomer. The derivatives fragmented in an analogous manner to that reported earlier for nicotinate derivatives of alcohols and picolinyl derivatives of carboxylic acids, with the production of a series of diagnostic ions formed by radical-induced cleavage of the chain following random hydrogen abstraction. Branched chain compounds, exemplified by glycerol ethers, gave spectra in which one of the ions diagnostic of the branch-point was missing. Unsaturated compounds, exemplified by the glycerol esters, gave characteristic mass spectra in which separation between ions representing formal cleavage at each side of the double bond enabled the position of this bond to be determined. In addition the spectra of unsaturated compounds contained two abundant ions whose formation could be rationalized by abstraction of the allylic hydrogen atoms. The nicotinylidene derivatives gave more diagnostic spectra than the methylnicotinylidene derivatives, whose spectra were complicated by the appearance of ions produced by loss of the methyl and pyridyl groups from the derivative. Both derivatives were superior to the nicotinate derivatives of these dihydroxy compounds in that only one pyridine residue was introduced on derivatization; this gave a lower molecular weight increment and allowed compounds with longer chains to be examined.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1883864 TI - Selected ion monitoring method for determination of nicotine, cotinine and deuterium-labeled analogs: absence of an isotope effect in the clearance of (S) nicotine-3',3'-d2 in humans. AB - A method for simultaneous determination of nicotine, its metabolite cotinine, and the stable isotope-labeled analogs nicotine-3',3'-d2 and cotinine-4',4'-d2 in human plasma has been developed. The method utilizes capillary column gas chromatography with detection by electron impact mass spectrometry and selected ion monitoring. Sensitivity is adequate for determination of nicotine and nicotine-d2 at concentrations as low as 1 ng ml-1, and cotinine and cotinine-d2 at concentrations as low as 10 ng ml-1 with good precision and accuracy. The method has been used to compare the elimination kinetics of (S)-nicotine-3',3'-d2 with natural nicotine in human subjects. Total clearance of nicotine-3',3'-d2 was virtually identical to the total clearance of natural nicotine, which validates the use of the deuterium-labeled analog in quantitative studies of nicotine metabolic disposition. PMID- 1883865 TI - Identification of cannabichromene metabolites by mass spectrometry: identification of eight new dihydroxy metabolites in the rabbit. AB - Metabolites of cannabichromene (CBC) produced by hepatic microsomal incubates from rabbits and mice were examined by gas chromatography/mass spectrometry (GC/MS) as trimethylsilyl (TMS) and (2H9)TMS derivatives. Most metabolites were hydroxylated compounds whose mass spectra gave very little information on metabolite structure as fragmentation was dominated by formation of the substituted chromenyl ion. This prevented charge localization and diagnostic fragmentation at the site of metabolic attack. This paper describes the identification of these metabolites by GC/MS techniques using both deuterium exchange reactions and hydrogenation of the metabolites to tetrahydro derivatives; the latter method was used to suppress chromenyl ion formation and to enhance the relative abundance of diagnostic fragment ions. Twenty-one metabolites were identified. Metabolites were found hydroxylated in all positions of both aliphatic chains, with additional compounds formed by epoxidation and reduction of the aliphatic double bond in the methylpentenyl chain. Dihydroxy metabolites were hydoxylated in both the pentyl and methylpentenyl chains in positions common to those hydroxylated in the monohydroxy metabolites. PMID- 1883866 TI - A moving belt device to couple high-performance liquid chromatography and chemical reaction interface mass spectrometry. AB - A device is described to enable selective detection of 13C- and 15N-labeled compounds following separation by high-performance liquid chromatography (HPLC). A thermospray vaporizer deposits the materials eluting from the HPLC column onto a continuously moving endless belt. The belt carries these compounds into the chemical reaction interface, where a microwave-induced helium plasma converts complex organic molecules in the presence of a reactant gas into small stable molecules that are detected by the mass spectrometer. Chromatograms showing only compounds enriched with 13C and 15N can be obtained by subtracting the abundance of naturally occurring isotopes from the observed M + 1 signal. This work demonstrates the feasibility of this approach and encourages its further development. PMID- 1883867 TI - Oligosaccharide sequence determination using B/E linked field scanning or tandem mass spectrometry of phosphatidylethanolamine derivatives. AB - Product ion mass spectral data of [M + H]+ ions of oligosaccharides, mainly tetra and pentasaccharides, as their dipalmitoyl phosphatidylethanolamine derivatives were obtained using both liquid secondary ion mass spectrometry with B/E linked scanning and fast atom bombardment ionization with collision-induced dissociation/tandem mass spectrometry. Both methods give similar positive product ion spectra of equivalent high sensitivity (detection limits of approximately 50 pmol) that principally contain glycosidic cleavage ions retaining the reducing end of the molecule from which monosaccharide sequence can be deduced. A series of ions from fission of the phosphate ester bond together with glycosidic cleavage are present in the tandem mass spectra and B/E linked scan spectra when helium collision gas is used. Monosaccharide linkage position of isomeric molecules is reflected in the intensity of glycosidic fragmentation, without retention of the oxygen atom, with decreasing cleavage in the order 1-3 greater than 1-4 greater than 1-6 linkage. Fucose and N-acetylhexosamines show an increased degree of fragmentation over hexose sugars. The application of product ion spectra of derivatized oligosaccharides is demonstrated for characterizing mixed samples and also the acquisition of spectra directly from the silica surface of high-performance thin-layer chromatography plates. PMID- 1883868 TI - Spontaneous fatal pulmonary thrombo-embolism in a mini-pig. AB - Spontaneous thrombo-embolism is an extremely rare disease in swine. We observed such a disease in a mini-pig. The animal attracted attention, because it did not eat its fill and breathed hamperally and shallowly but without stridor. Blood gas analysis and ECG findings indicated changes like in an acute pulmonary infection. 24 h after it had been admitted to our animal pasture the animal was dead. The reason was a pulmonary thrombo-embolism. PMID- 1883869 TI - Macroscopic and histologic study to differentiate large glands and bulbi in the perianal body region of the male gray short-tailed opossum, Monodelphis domestica. AB - On either side of the cloaca of the male Monodelphis domestica, there is a large pack of globular structures lying between the external skin and the ischial arch. The structures within each of these bilateral complexes can be classified into three groups. Group 1 comprises different kinds of glands. There are two large glands, "Paraproctic glands" according to Schaffer (1940), whose spacious cavity is bounded by a secretory epithelium. The secretion is holocrine in a way that cells are shed into the wide cavity. Further, there are two large bodies built of sebaceous acini around a central cavity. The inner surface of the cavity is a squamous stratified epithelium. A peripheral layer of secretory tubuli completes the structure's wall. The bodies are referred to as "Circumanal glands" according to Schaffer (1940). Their excretory ducts end into the cloaca. Group 2 is located between the glands of group 1 and group 3. Macroscopically, the structures of this group are easily mistaken as glands, however, histologically they are identified as a bilateral bulb of the corpus spongiosum, and as a bilateral bulb of the crus of the corpus cavernosum penis. Group 3 includes three different glands that end into a bilateral expansion of the urethra. These accessory genital glands are very distinct due to the histologic characteristics of their secretory epithelium. PMID- 1883870 TI - Impact of a privacy panel on the behavior of caged female rhesus monkeys living in pairs. AB - Thirty paired female rhesus monkeys were tested in a control situation when companions had no privacy, and in an experimental situation when they were offered the option to move behind a panel and be alone. Paired partners spent significantly more time in close proximity (same half of the cage) when the privacy panel was provided (means with panel = 76.0%/h vs. means no panel = 60.8%/h; p less than 0.005). At the same time, they were more engaged in affiliative interactions (means with panel = 37.4%/h vs. means no panel = 26.5%/h; p less than 0.025) while the incidence of agonistic interactions tended to decrease (means with panel = 0.3/h vs. means no panel = 2.2/h; p less than 0.1). It was concluded that rhesus monkeys have a need for companionship. They prefer to stay in close proximity with a compatible partner even though this may reduce their available cage space. It was further concluded that companions have no need for prolonged periods of visual seclusion, but occasional privacy is beneficial for their relationship. PMID- 1883871 TI - Streptococcus canis arthritis in a cat breeding colony. AB - This is the first description of a pathologic condition--arthritis in cats affecting mainly one joint, i.e. monarthritis--caused by Streptococcus canis (S. canis), of the Lancefield serologic group G. Six cases were recorded in a closed cat breeding colony during a 6 month period in 1988, and one additional case in 1990. Therapy with penicillin and streptomycin led to full recovery in four of six cases. The bacterium had been detected from different purulent processes sporadically--including one case of purulent arthritis in 1982--as a nosocomial infection since 1980, the year the breeding colony was established. A possible genetic predisposition (high inbreeding) may have contributed to the accumulation of the six cases in 1988. Although S. canis was isolated in mouse, rat, rabbit and dog, cat and man seem to be more frequently affected. There are some similarities between S. canis-arthritis in cat and man. PMID- 1883872 TI - Serum cortisol concentrations of single-housed and isosexually pair-housed adult rhesus macaques. AB - Possible social distress was evaluated in 20 adult rhesus macaques housed in compatible isosexual pairs (5 female pairs, 5 male pairs) for the purpose of social environmental enrichment. Serum cortisol concentrations of paired animals were compared with serum cortisol concentrations of individually housed adult rhesus macaques of both sexes (5 females, 5 males). In both sexes, cortisol concentrations of paired animals (means 10 females = 19.5 +/- 2.9 micrograms/dl; means 10 males = 17.5 +/- 4.6 micrograms/dl) showed no significant difference (p always greater than 0.1) with those of single animals (means 5 females = 20.5 +/- 2.1 micrograms/dl; means 5 males = 15.9 +/- 2.6 micrograms/dl). Both in male and in female pairs, dominant partners had cortisol concentrations that were equivalent to those of their subordinate counterparts. It was concluded that neither female nor male adult rhesus macaques experience more distress when sharing a cage with a compatible partner of the same sex than when living alone. PMID- 1883873 TI - A function for the integrin alpha 6 beta 4 in the hemidesmosome. AB - Many epithelial cells appear to use cell-substratum adhesion complexes known as hemidesmosomes as the main means of anchorage to the connective tissue. Initially recognized as distinctive electron-dense images, hemidesmosomes are still poorly understood at the biochemical level. The regulation and mode of their assembly, which is disrupted in certain blistering diseases and is critical to proper wound repair, also remains to be elucidated. The integrin alpha 6 beta 4 is expressed along the basal surface of various epithelial cells. We show here that this integrin localizes to hemidesmosomes as determined by immunoelectron microscopy using antibodies directed against both the extra- and intracytoplasmic domains of alpha 6 beta 4. This result, which agrees with a recent study, suggests a functional role for the alpha 6 beta 4 integrin in the hemidesmosomes. We therefore investigated such a potential role for this integrin using the cultured rat bladder carcinoma cell line 804G, which has the uncommon ability to form hemidesmosomes in vitro when maintained on uncoated glass substrates. By immunoprecipitation and immunofluorescence, we show that 804G cells express alpha 6 beta 4 along their basal surface in a punctate pattern that overlaps with the distribution of hemidesmosomal plaque antigens. However, this pattern is altered when cells are plated in the presence of an antiserum directed against alpha 6 beta 4. Furthermore, no hemidesmosomes are detectable at the ultrastructural level in the alpha 6 beta 4 antibody-treated cells compared with control cells. These results indicate that integrins may play a critical role in assembly and adhesive functions of the hemidesmosome. PMID- 1883875 TI - Localization of transforming growth factor-beta 1 in mitochondria of murine heart and liver. AB - Using both electron microscopic immunohistochemistry and cell fractionation techniques, we show that transforming growth factor-beta 1 (TGF-beta 1) is found in mitochondria of rat and mouse cardiac myocytes and rat hepatocytes. Four different polyclonal antibodies, raised against various epitopes encompassing the mature portion of the TGF-beta 1 molecule as well as the pro-region of its precursor, were used for the electron microscopy studies. The localization of TGF beta 1 in mitochondria was confirmed by detection of the native peptide in mitochondria isolated from rat heart and liver; the majority of native TGF-beta 1 found in liver homogenates was recovered in highly pure mitochondrial fractions. The functional role of TGF-beta in the mitochondrion is unknown at present. PMID- 1883874 TI - sar1, a gene from Schizosaccharomyces pombe encoding a protein that regulates ras1. AB - Proper ras1 function is required for normal sexual function in the yeast Schizosaccharomyces pombe. We have found a gene in S. pombe, sar1, that encodes a product capable of regulating ras1 function. sar1 is a member of an expanding family of RAS GTPase-activating proteins (GAPs) that includes mammalian GAP, the yeast Saccharomyces cerevisiae IRA proteins, and the product of the human neurofibromatosis locus, NF1 sar1, like these other proteins, can complement the loss of IRA function in S. cerevisiae. Computer analysis shows that the highest degree of sequence conservation is restricted to a very small number of diagnostic residues represented by the motif Phe-Leu-Arg-X-X-X-Pro-Ala-X-X-X-Pro. We find no evidence that sar1 is required for the effector function of ras1. PMID- 1883876 TI - RecA and related proteins: from recombination to SOS functions. Part I. Proceedings of a meeting. Saclay, France, September 17-21, 1990. PMID- 1883877 TI - RecA protein in the SOS response: milestones and mysteries. AB - The role of RecA protein in the SOS response of Escherichia coli is traced from the isolation of the first recA mutant to our current understanding of the scope and regulation of this DNA damage-inducible system. In addition, possible RecA protein activities that may be essential in the expression of several SOS phenotypes (stable DNA replication, DNA replication recovery, SOS mutagenesis and RecA association with the cell membrane) are discussed. PMID- 1883878 TI - Dynamic light scattering investigations of RecA self-assembly and interactions with single strand DNA. AB - Dynamic light scattering (DLS) measurements were performed on self-assembled solutions of RecA as a function of assembly time under strand exchange ionic strength conditions (10 mM MgCl2, 65 mM NaCl, 10 mM Tris-HCl, pH = 7.5, 1 mM DTT, 3-4 microM RecA) in the absence of ATP. These measurements yield distributions of the translational diffusion coefficients of the changing populations of assembling protein species. Interpretations of results of DLS measurements are made in terms of model hydrodynamic calculations that indicate, under the solution conditions employed, the smallest fundamental quaternary subunit of RecA is a hexamer in a toroidal or lock-washer configuration. Interactions of M13mp19 circular single strand DNA (ssDNA) with RecA assembled to different stages were also investigated. Additions of ssDNA to self-assembled solutions of RecA acts to dissociate the associated structures into hexamer subunits. However, the effect of ssDNA on assembled RecA is highly dependent on the RecA self-assembly state. The longer the assembly time, the less reversible the self-assembled structures of RecA become. Binding isotherms of titrated mixtures of ssDNA with RecA self assembled to various stages were also determined. Evaluated dissociation constants of RecA/ssDNA complexes were found to increase with increases of the associated state of RecA. These results strongly suggest that, under the solvent conditions employed, the active ssDNA binding form of RecA is a hexamer. PMID- 1883879 TI - RecA protein-promoted homologous pairing between duplex molecules: functional role of duplex regions of gapped duplex DNA. AB - RecA protein promotes homologous pairing and symmetrical strand exchange between partially single-stranded duplex DNA and fully duplex molecules. We constructed circular gapped DNA with a defined gap length and studied the pairing reaction between the gapped substrate and fully duplex DNA. RecA protein polymerizes onto the single-stranded and duplex regions of the gapped DNA to form a nucleoprotein filament. The formation of such filaments requires a stoichiometric amount of RecA protein. Both the rate and yield of joint molecule formation were reduced when the pairing reaction was carried out in the presence of a sub-saturating amount of RecA protein. The amount of RecA protein required for optimal pairing corresponds to the binding site size of RecA protein at saturation on duplex DNA. The result suggests that in the 4-stranded system the single-stranded as well as the duplex regions are involved in pairing. By using fully duplex DNA that shares different lengths and regions of homology with the gapped molecule, we directly showed that the duplex region of the gapped DNA increased both the rate and yield of joint molecule formation. The present study indicates that even though strand exchange in the 4-stranded system must require the presence of a single-stranded region, the pairing that occurs in duplex regions between DNA molecules is functionally significant and contributes to the overall activity of the gapped DNA. PMID- 1883880 TI - Head to head dimer model; an alternative model for the strand exchange reaction by RecA protein of Escherichia coli. AB - The RecA protein of E coli promotes a strand exchange reaction in vitro which appears to be similar to homologous genetic recombination in vivo. A model for the mechanism of strand transfer reaction by RecA protein has been proposed by Howard-Flanders et al based on the assumption that the RecA monomer has two distinctive DNA binding sites both of which can bind to ssDNA as well as dsDNA. Here, I propose an alternative model based on the assumption that RecA monomer has a single domain for binding to a polynucleotide chain with a unique polarity. In addition, the model is based on a few mechanical assumptions that, in the presence of ATP, two RecA molecules form a head to head dimer as the basic binding unit to DNA, and that the binding of RecA protein to a polynucleotide chain induces a structural change of RecA protein that causes a higher state of affinity for another RecA molecule that is expressed as cooperativy. The model explains many of the biochemical capabilities of RecA protein including the polar polymerization of RecA protein on single stranded DNA and polar strand transfer of DNA by the protein as well as the formation of a joint DNA molecule in a paranemic configuration. The model also presents the energetics in the strand transfer reaction. PMID- 1883881 TI - On the polymerization state of recA in the absence of DNA. AB - We present an electron microscopy study on the polymerization state of recA in the absence of DNA. In solution recA exists as monomers, small complexes not clearly longer than wide (approximately 9-18 nm), and filaments (diameter approximately 11 nm and variable lengths). We have attempted to quantify the relative amounts of these species by length measurements of the particles on electron micrographs. The percentages of each of these types was found to depend on recA concentration, temperature and presence in the incubation mixture of Mg2+, ATP gamma S, salt or D2O. These additives do not have an absolute effect on polymerization but rather shift the polymerization equilibrium of recA (which depends on recA concentration) up or down the concentration scale. PMID- 1883882 TI - RecA-DNA helical filaments in genetic recombination. AB - Paul Howard-Flanders et al proposed a molecular model of RecA-mediated recombination reaction six years ago. How does this model stand at present? In answering this question, we focus on two leading ideas of the original model, namely the proposal of the coaxial arrangement of the aligned DNA molecules within helical RecA filaments and the proposal of the ATP independence of the pairing stage of the recombination reaction. Results obtained after the model was proposed are reviewed and compared with these original assumptions and postulates of the model. EM visualization of recombining DNA molecules, studies of the energetics of the RecA-mediated recombination reaction and biochemical analysis of deproteinized joint molecules are fully consistent with a triple-stranded DNA arrangement during the RecA-mediated recombination reaction and demonstrate the ATP independence of the pairing stage of the reaction. PMID- 1883883 TI - Co-ordination of multiple DNA molecules in RecA fiber evidenced by linear dichroism spectroscopy. AB - Polarized light spectroscopy has been used to study the interaction of RecA protein with DNA. Several different DNA complexes have been identified and characterized with respect to stoichiometries, base orientation and nuclease accessibility. By using spectroscopically distinguishable DNAs, we determined the number of DNA molecules co-ordinated by the RecA fiber in each of these complexes, and established their base pairing abilities. Based on these observations, we discuss the molecular mechanism of the RecA-mediated strand exchange reaction. PMID- 1883884 TI - The solution structure of recA filaments by small angle neutron scattering. AB - The technique of small angle neutron scattering has been applied to study the structure in solution of recA self-polymers and various recA-DNA complexes. These results are compared with those recently obtained by other physical techniques. PMID- 1883885 TI - Saccharomyces cerevisiae proteins involved in hybrid DNA formation in vitro. AB - RecA-like activities that can form hybrid DNA in vitro have been identified in a wide variety of organisms. We have previously described the strand exchange protein 1 (SEP1) from the yeast Saccharomyces cerevisiae that can form hybrid DNA in vitro. Purified as an Mr 132,000 polypeptide, recent molecular and immunological studies have now shown that the native form is an Mr 175,000 polypeptide containing strand exchange activity. The gene encoding SEP1 has been cloned and sequenced. The primary sequence failed to reveal any significant sequence homology to other sequences in data base searches. In vivo SEP1 was found to be essential for normal meiosis as cells containing a homozygous insertion mutation in the SEP1 gene failed to sporulate. In order to identify additional factors that are involved in hybrid DNA formation in S cerevisiae, we used an in vitro stimulation assay to identify proteins that reconstitute strand exchange activity in reactions containing limiting amounts of SEP1. We have identified two proteins that functionally interact with SEP1. First, an Mr 34,000 single-stranded DNA binding protein stimulated the reaction by lowering the requirement for SEP1 about 3-4 fold. This protein is a fragment of the large subunit of a hetero-trimeric complex called yRP-A (yRF-A) which is thought to be the functional eukaryotic equivalent of single-stranded DNA binding proteins in prokaryotes. The gene encoding this protein (RPA1) is essential for growth. Second, an Mr 33,000 polypeptide, termed Stimulatory Factor 1 (SF1), dramatically stimulated the SEP1 catalyzed reaction by lowering the requirement for SEP1 about 300 fold.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1883886 TI - Site-directed mutagenesis in the Escherichia coli recA gene. AB - Escherichia coli RecA protein plays a fundamental role in genetic recombination and in regulation and expression of the SOS response. We have constructed 6 mutants in the recA gene by site-directed mutagenesis, 5 of which were located in the vicinity of the recA430 mutation responsible for a coprotease deficient phenotype and one which was at the Tyr 264 site. We have analysed the capacity of these mutants to accomplish recombination and to express SOS functions. Our results suggest that the region including amino acid 204 and at least 7 amino acids downstream interacts not only with LexA protein but also with ATP. In addition, the mutation at Tyr 264 shows that this amino acid is essential for RecA activities in vivo, probably because of its involvement in an ATP binding site, as previously shown in vitro. PMID- 1883887 TI - Expression of the Escherichia coli recA gene in the yeast Saccharomyces cerevisiae. AB - The isolation of the protein coding region of the recA gene from Escherichia coli by extensive Bal31 digestion is described. The structural recA gene was ligated into an extrachromosomally replicating yeast expression vector, downstream of the yeast alcohol-dehydrogenase gene promoter region, to produce pADHrecA plasmid. The pADHrecA plasmid was transformed into the wild-type and the repair deficient strains of Saccharomyces cerevisiae. The crude protein samples were extracted from the individual yeast transformants. A 38 kDa protein was present in all transformants containing the recA gene on plasmid. Thus the recA gene from E coli was successfully expressed in cells from a lower eukaryote. PMID- 1883888 TI - Biochemical and biological function of Escherichia coli RecA protein: behavior of mutant RecA proteins. AB - The recA protein of E coli participates in several diverse biological processes and promotes a variety of complex in vitro reactions. A careful comparison of the phenotypic behavior of E coli recA mutations to the biochemical properties of the corresponding mutant proteins reveals a close parallel both between recombination phenotype and DNA strand exchange and renaturation activities, and between inducible phenomena and repressor cleavage activity. The biochemical alterations manifest by the mutant recA proteins are reflected in the strength of their interaction with ssDNA. The defective mutant recA proteins fail to properly assume the high-affinity DNA-binding state that is characteristic of the wild type protein and, consequently, form less stable complexes with DNA. The mutant proteins displaying an 'enhanced' activity bind ssDNA with approximately the same affinity as the wild-type protein but, due to altered protein-protein interactions, they associate more rapidly with ssDNA. These changes proportionately affect the ability of recA protein to compete with SSB protein, to interact with dsDNA, and, perhaps, to bind repressor proteins. In turn, the DNA strand exchange, DNA renaturation, and repressor cleavage activities mirror these modifications. PMID- 1883889 TI - Overlapping functions of recD, recJ and recN provide evidence of three epistatic groups of genes in Escherichia coli recombination and DNA repair. AB - The recD, recJ and recN genes of Escherichia coli K-12 have been shown to be involved in genetic recombination and DNA repair in this organism. Yet, mutation of any one of these genes does not seem to interfere much with the recovery of recombinants from conjugational crosses. Strains carrying all possible combinations of mutations inactivating these genes were constructed and examined for their recombination proficiency and sensitivity to UV light. The recD recJ and recJ recN double mutants are moderately sensitive to UV light and slightly deficient in recombination. A combination of mutations in all 3 genes produced strains that are very deficient in recombination (50- to 100-fold reduction) and strikingly sensitive to UV light. We conclude that these genes provide overlapping activities that compensate for one another in the single mutants. On the basis of these and other data, recombination genes are classified into 3 epistatic groups that define activities which function pre-synaptically or post synaptically to promote genetic exchanges catalysed by RecA. PMID- 1883890 TI - Positive and negative regulatory elements in the dnaA-dnaN-recF operon of Escherichia coli. AB - The recF gene of E coli lies within a cluster of genes which play essential roles in DNA replication; the gene order is dnaA dnaN recF gyrB. Each of these genes has its own promoters which, with the exception of dnaA promoters, reside entirely within the translated region of the respective preceding gene. In this report, we analyze the effect of the dnaA and dnaN promoters on recF expression by translational fusions between recF and the lacZ reporter gene. Our results indicate that recF is a distal gene of the dnaA operon, and support the previous proposal that dnaN and recF constitute a transcriptional unit under control of the dnaN promoters. They also suggest that dnaA, dnaN and recF are predominantly expressed from the same mRNA although transcriptional and/or post-transcriptional mechanisms should be specifically involved in lowering expression of the recF gene. Recently, we have localized 3 tandem transcription termination sites in the second half of the dnaN gene, downstream from the recF promoters. Neither of them shows the typical features of simple terminators and apparently they do not work in a minimal system of in vitro transcription. In this report, we present evidence that only one of them is dependent on the Rho protein. Although the operon structure allows coordinate expression of dnaA, dnaN and recF, the presence of internal promoters (the dnaN and recF promoters), which appear to be inducible by DNA damage, and intracistronic terminators, whose activity is inversely proportional to the efficiency of translation, permits expression of individual genes to be independently regulated in response to altered growth conditions. PMID- 1883892 TI - Enzyme test monitors periodontal disease status. PMID- 1883891 TI - Cloning and preliminary characterization of srf-2020 and srf-801, the recF partial suppressor mutations which map in recA of Escherichia coli K-12. AB - We have located the single nucleotide changes suffered in recA sequence of 2 recF partial suppressor mutations: srf-2020 at codon 121 and srf-801 at codon 257. srf 2020 changes codon 121 from threonine (ACC) to isoleucine (ATC). srf-801 changes codon 257 from glutamine (CAG) to proline (CCG). Consequently these mutations were renamed recA2020 and recA801 respectively. Preliminary characterization of recA2020 revealed that it is transdominant to recA+, like recA803, another recF partial suppressor. Interactions of recA2020 with recA803 were examined using genetic studies. Heterozygotes containing recA2020 and recA803 failed to produce a synergistic suppression effect in suppressing the recF deficiency. Presence of both recA2020 and recA803 mutations in the same recA gene also failed to produce any greater amount of UV resistance to a uvrA6recF143del(recA) strain indicating no interactions between these suppressors. PMID- 1883894 TI - Combination fixed/removable implant prosthetics using spark erosion technology. PMID- 1883893 TI - The Kulzer abutment luting; Kal technique. A direct assembly framework method for osseointegrated implant prostheses. PMID- 1883895 TI - The accuracy verification stent (AVS) technique. PMID- 1883896 TI - Periimplantitis, the ailing implant. PMID- 1883897 TI - A modified technique from the complete mandibular subperiosteal implant. The anterior mandibular subperiosteal implant. Case report. PMID- 1883898 TI - Cast titanium: an improvement in implant prosthetics. PMID- 1883899 TI - RadioVisioGraphy: instant radiographic images aid implant treatment, maintenance. PMID- 1883901 TI - The role of the radiologist in implantology. PMID- 1883900 TI - Immediate placement of dental implants after extractions. More cases. PMID- 1883902 TI - Current applications of the dental laser in implantology. PMID- 1883903 TI - [Interaction of carbonic acid reamination and oxidation processes at various functional states of tissue]. AB - The metabolic pathways of generation and oxidation of di- and tricarboxylic acids in mitochondria differ under the resting state and during the stimulation of energy metabolism coupled with the activation of physiological functions. The contribution of amino acids to the respiration via glutamate transamination is greater during stimulation of energy metabolism than in the resting state. This may account for the increased contribution to mitochondrial respiration of succinate, the most powerful energy source among TCA substrates. The increase of succinate in the respiration is especially apparent after addition of physiological concentrations of succinate (0.3-1.0 mM). The relationship between transamination and respiration was observed during short-term experiments with mitochondria preserving their native structure. This interaction was lost in damaged mitochondria under conditions of TCA discovery. PMID- 1883904 TI - [The effect of metabolites of the propionate pathway on the oxidative activity of liver mitochondria]. AB - Methylmalonate and propionate, the major metabolites of the propionate pathway of fatty and amino acid metabolism used at 1-4 mM cause selective inhibition of succinate and palmitoyl carnitine oxidation in liver mitochondria. Methylmalonate is more specific towards succinate, whereas propionate--towards palmitoyl carnitine oxidation. Methylmalonate is transported to mitochondria at a high rate with no effect on succinate transport. Being injected intramusculary methylmalonate has no inhibiting effect on the oxidative activity of mitochondria but is able to activate succinate and palmitoyl carnitine oxidation. The inhibiting effect of propionate on palmitoyl carnitine oxidation is a long-term one. Injections of these metabolites precursors, isoleucine, methionine and valine, produce an activating effect on succinate oxidation. Thus, propionate pathway metabolites may participate in the regulation of lipid-carbohydrate metabolism. PMID- 1883905 TI - [Control of the energizing of liver mitochondria at the adenine nucleotide carrier level under hypotonic conditions]. AB - The effects of ADP, carboxyatractyloside (CAT) and the local anaesthetic nupercaine on the energy-dependent Ca2+ uptake by rat liver mitochondria oxidizing succinate in the presence of oligomycin were compared, using incubation media of 320 mosM and 120 mosM tonicities. In hypotonic media the mitochondrial Ca2+ capacity was increased by 50%, and the mitochondria were more stable to the damaging effects of Ca + Pi. In the presence of ADP the Ca2+ capacities of mitochondria increased both in normotonic and hypotonic media; however, the absolute amounts of calcium consumed were levelled off. CAT abolished the effect of ADP on the mitochondrial Ca2+ uptake and equalized the Ca2+ capacities of rat liver mitochondria in the both media. The local anaesthetic nupercaine also increased the Ca2+ capacity of mitochondria. The effects of nupercaine and ADP were additive. CAT abolished the effect of ADP but not that of nupercaine. Measurements of the intramitochondrial contents of adenine nucleotides showed that in 120 mosM media there was a significant increase in the intramitochondrial content of ATP and the total pool of adenine nucleotides. It was concluded that in hypotonic media the mitochondrial adenine nucleotide carrier exists predominantly in the m-conformation thus facilitating the energization of mitochondria. PMID- 1883906 TI - [Proteolytic activity of the Glu-plasminogen complex with fibrinogen fragment E]. AB - Glu-plasminogen interaction with fibrinogen fragment E results in the alteration of its adsorptive capacity. During this interaction in the absence of plasmin and tissue activator of plasminogen, Glu-plasminogen is transformed into a partly degraded form. Glu-plasminogen complexes with soluble and immobilized fibrinogen fragment E. contain a serine proteinase-specific activity which is inhibited by diisopropylfluorophosphate. The complexes under study are active towards fibrin and the plasmin-specific tripeptide substrate, D-Val-L-Leu-L-Lys-p-nitroanilide. It is concluded that fibrinogen fragment E induces structural changes in the enzyme molecule which eventually result in the formation of an active center. PMID- 1883907 TI - [The effect of cyclosporin A and oligomycin on the nonspecific permeability of the mitochondria inner membrane]. AB - The effect of oligomycin and cyclosporine A on Ca(2+)-induced nonspecific permeability of the inner mitochondrial membrane was under study. Both oligomycin and cyclosporine A were able to prevent the activation of nonspecific permeability; however, but cyclosporine A was the only agent which could restore the initial permeability of the inner mitochondrial membrane. The effect of cyclosporine A was not shown to be mediated through redistribution of Ca2+ ions between different subpopulations of mitochondria. PMID- 1883908 TI - [The role of the ADP/ATP-antiporter in the inhibition of nonspecific permeability of the inner mitochondrial membrane by cyclosporin A]. AB - The effect of the conformational state of the ADP/ATP-antiporter on the efficiency of inhibition by cyclosporine A of the Ca(2+)-induced increase of nonspecific permeability of the inner mitochondrial membrane was under study. It was found that the ADP/ATP-antiporter inhibitor carboxyatractyloside is able to reverse the cyclosporine A-induced inhibition of this nonspecific permeability. The effect of carbocyatractyloside is manifested only in mitochondria depleted of adenine nucleotides. The bifunctional SH-reagent phenylarsine oxide is also able to reverse the cyclosporine A effect. The data obtained testify to the fact that inhibition by cyclosporine A of nonspecific permeability is due to its effect on the conformational state of the ADP/ATP-antiporter. PMID- 1883909 TI - [The role of malate in regulating the rate of mitochondrial respiration in vitro]. AB - Depletion of endogenous malate by preincubation of mitochondria at 30 degrees C in substrate-free media sharply decreases the rate of citrate oxidation and inhibits mitochondrial respiration in the presence of pyruvate and alpha ketoglutarate. Addition of catalytic amounts of endogenous malate and its production via succinate oxidation promote rapid oxidation of citrate and pyruvate in the mitochondria and abolishes the lag period with alpha ketoglutarate Malate increases the rate of membrane potential generation after addition of citrate, pyruvate or alpha-ketoglutarate to mitochondrial suspensions. Studies with controlled malate concentrations revealed that the changes in malate concentrations observed in the mitochondria in the presence of gluconeogenesis-inducing hormones may be due to the influence of these hormones on mitochondrial oxidation. PMID- 1883910 TI - [Cleavage of concatamer-type substrates by restriction endonucleases MVA1 and SSO1I]. AB - The interaction of enzymes SsoII (decreases CCNGG) and MvaI (CC decreases A/TGG) with concatemeric DNA duplexes used earlier to study EcoRII (decreases CCA/TGG) TGG was investigated with a view of elucidating the general principles of the restriction endonuclease function. A pattern common for all the three enzymes was observed with DNA duplexes containing AA or TT pairs in the central position of the recognition site. The AA pair blocks or substantially hinders the endonuclease action, whereas the TT pair is either less inhibitory or altogether inert. SsoII, similar to EcoRII was able to processively cleave the concatemeric substrates and to interact with (or to be close to) the hydrogen in the 5th position of the outer dC residue of the recognition site. MvaI was found to differ from EcoRII in the way they recognize and cleave the same nucleotide sequence. The substrate-bound MvaI molecule is incapable of linear diffusion along the DNA. Effective hydrolysis of dU- and m5dC-containing polymers rules out the participation of hydrophobic contacts of the enzyme with the methyl group of the dT residue and with the 5th hydrogen of the outer dC residue of the recognition site in DNA-protein interactions. PMID- 1883911 TI - [Gangliosides GM3 and GD3 in human stomach and breast tumors]. AB - Gangliosides of human gastric and mammary tumours and of homologous normal tissues were studied by using biochemical methods and specific antisera. It was found that in most cases GM3, GD3 and GM1 are predominant gangliosides, whereas several polar components are minor ones. A comparison of the relative amount of ganglioside fractions revealed that in gastric tumours the per cent content of polar compounds is higher than in intact tissue; however, the absolute content of all gangliosides is markedly increased. A comparative study of the composition of mammary tumour and normal tissue gangliosides demonstrated two types of changes: i) the absolute content of all gangliosides in tumour tissue was increased and, ii) the increase in the content of total gangliosides was paralleled with the appearance of a new fraction (presumably GM4), the decrease of the GD3 content and the disappearance of polar gangliosides. A possible mechanism of this effect is discussed. PMID- 1883912 TI - The effects of interleukin-2 on bone marrow engraftment in a murine model. AB - Strategies have been developed to rid bone marrow of microscopic tumor prior to infusion in the autologous bone marrow transplant setting. We have previously demonstrated that recombinant human interleukin-2 (IL-2) is effective in such an experimental setting involving a methylcholanthrene-induced fibrosarcoma in mice. The purpose of the current work was to determine whether IL-2 treatment after, or before and after bone marrow transplantation would influence bone marrow engraftment or degree of hematologic reconstitution. We found that stem cell number (CFU-S) and posttransplant marrow cellularity were comparable in IL-2 treated or saline-treated mice. Furthermore, after engraftment, marrow stem cell and myeloid progenitor cell numbers were greater in the IL-2 treatment group. These results suggest that IL-2 will prove to be safe when administered in bone marrow transplant patients. PMID- 1883913 TI - Effects of intracarotid and intravenous infusion of human TNF and LT on established intracerebral rat gliomas. AB - The effects of recombinant human tumor necrosis factor (TNF) and lymphotoxin (LT) were investigated against two different established rat gliomas. Single preestablished intracarotid (ic) or intravenous (iv) doses (1.5-2.0 x 10(6) units) were administered to Wistar rats with intracerebral C6 gliomas and Fischer 344 rats with intracerebral T9 gliomas. Five days after cytokine treatment, animals were sacrificed and tumor size determined by histopathologic techniques. In Wister rats, ic TNF produced a greater reduction in size of C6 tumors than iv TNF. Experiments with Fischer rats showed that both TNF and LT were more effective when administered ic compared to iv. Furthermore, LT induced a greater reduction in tumor size than TNF. Additional studies on the age-related susceptibility of these gliomas revealed early, 8-day tumors were more sensitive to ic LT than advanced, 14-day tumors. No direct toxicity of these cytokines against the tumor cells was detected in vitro indicating their autitumor effect was mediated by alternate mechanisms in vivo. Thus for regionally confined gliomas ic therapy was superior to iv therapy and LT was more effective than TNF. Cytokine treatment was most effective on earlier tumors and there appeared to be differences in efficacy related to the tumor-host combination. PMID- 1883914 TI - Induction of cytokines in normal placental cells by the human immunodeficiency virus. AB - Placental cotyledon mononuclear cells (CMC) resemble peripheral blood monocytes/marcophages (MM) with respect to their expression of surface antigens and cellular function. CMC also express the CD4 antigen receptor and are thus susceptible to infection with the human immunodeficiency virus (HIV). When vertical transmission of HIV from mother to fetus occurs, the infection often remains latent until appropriate factors initiate the transcription of virus specific mRNA. Cytokines, such as interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6) which are produced by MM, up regulate HIV expression in infected cells. The induction of cytokines in MM does not require active infection with HIV since heat-inactivated HIV (iHIV) and envelope gp120 caused cytokine secretion. We studied the ability of CMC from normal placentas to secrete these cytokines following stimulation with endotoxin, iHIV, recombinant GP160 and GAG55, and synthetic p17, HGP-30. Whereas CMC spontaneously secreted low levels of IL-1 beta and TNF-alpha, they constitutively secreted high levels of IL-6. All cytokine levels could be boosted by endotoxin. GP160, iHIV, and HGP-30 failed to augment cytokine levels above baseline. In contrast, GAG55 significantly boosted only TNF-alpha. The relevance of these findings is discussed with respect to the putative roles of cytokines in the immunoregulation of HIV in utero. PMID- 1883915 TI - Biological function of recombinant IL-6 expressed in a baculovirus system. AB - The cDNA of human interleukin-6 (IL-6) was cloned into baculovirus DNA. Insect cells (Spodoptera frugiperda cells) infected with the recombinant baculovirus secreted a large amount of 22K protein into the culture medium. This culture fluid contained high biological activity of growth stimulation of a mouse myeloid cell line (MH-60). The IL-6 was purified by a one-step procedure employing immunoaffinity chromatography of monoclonal antibody to IL-6. The specific activities (BSF-2 reference units/mg protein) of the original culture medium and the purified material from the one-step purification were 0.3-1 x 10(6) and greater than 2 x 10(7), respectively. The highly purified IL-6 could not induce an antiviral state in human diploid fibroblast (FS-4) cells. PMID- 1883916 TI - Quantitative characterization of the intrinsic ligand-binding affinity of the interleukin 2 receptor beta chain and its modulation by the alpha chain and a second affinity-modulating element. AB - The interleukin 2 receptor is a multisubunit receptor known to consist of at least two IL-2 binding subunits, alpha and beta. We report here kinetic evidence defining the contribution of an affinity-modulating element(s) intimately involved in modulation of the ligand-binding affinity of the beta chain and alpha/beta complex. The principal effect of this modulating element on the beta chain is to slow the dissociation of IL-2 more than 150-fold and thus raise its low intrinsic IL-2 binding affinity (Kd = 70 nM) as defined in transfected fibroblast cells to the level observed in lymphoid cells (Kd = 1.2 nM). The alpha subunit also increases the ligand-binding affinity of the beta chain, although in this case principally by increasing the association rate constant more than 1200 fold. The additional effect of the affinity-modulating element on the alpha/beta complex is minimal with regards to the equilibrium binding affinity. It does, however, have a detectable 14-fold effect on slowing the IL-2 dissociation rate. The existence of multiple forms of IL-2 receptor complexes with widely varying ligand affinities and dissociation rates illustrates the need for careful evaluation of binding data in studies of receptor subunit composition and reconstitution. PMID- 1883917 TI - Cytokine production by the bladder carcinoma cell line 5637: rapid analysis of mRNA expression levels using a cDNA-PCR procedure. AB - We have studied cytokine expression by the human bladder carcinoma cell line 5637 using a cDNA-PCR procedure. Transcripts for interleukin-1 alpha (IL-1 alpha), IL 1 beta, IL-6, IL-7, IL-8, granulocyte-macrophage colony-stimulating factor (GM CSF), G-CSF, M-CSF, tumor-necrosis factor-alpha (TNF-alpha), and TNF-beta were constitutively present, whereas IL-3, IL-4, IL-5, and IL-9 mRNA sequences could not be detected. This expression pattern was not altered after 12-O-tetradecanoyl phorbol-13-acetate (TPA) stimulation (4 and 8 h) of 5637 cells. Relative expression levels of cytokines were assessed by limiting dilution of the cDNA pool. This procedure proved to be a semiquantitative technique when compared to Northern blot analysis. PMID- 1883918 TI - Some presentations on TGF-beta, MIP-1, and newly identified hematopoietic inhibitors at the Second International Conference on Negative Regulators of Hematopoiesis (Providence, August 22-25, 1990). PMID- 1883919 TI - Multifactorial analysis in the prognosis of ischemic cerebrovascular accidents. AB - An attempt to determine the prognosis of an individual patient with ischemic cerebrovascular accident means an attempt to take into consideration several parameters at the same time. Discrimination analysis was done as a retrospective study of 316 patients, who were followed from the moment of accident (admitted to the clinic within 24 hours), to four weeks after the accident. Nineteen parameters were determined by degree and correlated with the outcome through statistical significance of a single parameter p less than 0.05). After that, the parameters with statistical significance (age, state of consciousness, severity of motor deficit, previous episodes of cerebrovascular disease, Babinski sign, conjugate deviation of eyes, the way of onset of the disease) were used in a multifactorial analysis. The first analysis referred to the prognosis of survival (76 patients died, 240 patients survived). It was shown that the chosen parameters were satisfactory, since in 87% of cases they divided groups in an appropriate way, i.e. the group of deceased patients amounted to 76% and for the group of survived patients the score amounted to 90%. The second analysis referred only to patients who survived, with the aim to determine the probability of the quality outcome prognosis. It was shown that the same parameters were less reliable and the classification into two groups was done in 76% of cases (for--no deficit or small deficit group--in 73% of cases and for--severe deficit group--in 84% of cases. PMID- 1883920 TI - Entry of ciprofloxacin into cerebrospinal fluid during bacterial, viral and tuberculous meningitis. AB - We studied the entry of ciprofloxacin into the cerebrospinal fluid (CSF) in 37 patients with various types of meningitis (bacterial meningitis 10 patients, viral 12 patients, tuberculous 7 patients). Eight patients were in the control group with normal CSF finding. Mean ciprofloxacin concentrations in the CSF 50-60 minutes after 200 mg of ciprofloxacin was given in infusion were 0.20 +/- 0.12 mg/L in patients with bacterial meningitis, which was significantly higher than in other tested groups (p = 0.0325). Ciprofloxacin achieved concentrations in the CSF 6.5-39% of serum (mean value 15% +/- 9%) in the bacterial meningitis group, while in the groups with viral and tuberculous meningitis the levels were significantly lower (approximately 9% of serum) but still higher than in the control group (approximately 5% of serum). Our data suggest that ciprofloxacin should be very cautiously used in selected patients with bacterial meningitis caused by multiple resistant strains of gram negative bacteria. PMID- 1883921 TI - Principal advantages of CNS diagnostics by magnetic resonance imaging. AB - In this paper the authors present the principal advantages and values of CNS diagnostics by magnetic resonance imaging (MRI), on the basis of the data from the available literature as well as on the 3-year experience of the MRI Institute in Innsbruck. Also, qualitative advantages of MR 1.5 T over other, less powerful machines, have been emphasized. So far, the experience has proved that, for the moment, the 1.5 MR machine offers optimal characteristics for the diagnostics of the CNS diseases. PMID- 1883922 TI - The H or F wave latencies in medial gastrocnemius in the electrodiagnostic study of sciatica patients with suspected S1 radiculopathy. AB - The aim of this study was to test H or F wave latencies of medial head of gastrocnemius muscle for electrodiagnostic evaluation of patients with suspected S1 radiculopathy with or without additional L5 radiculopathy. A group of 97 patients (34 female and 63 male), aged 20-60 (average 44 years), with clinically suspected unilateral radiculopathy were studied. Needle EMG of medial gastrocnemius muscle was supplemented by H or F wave latencies measurement bilaterally by percutaneous stimulation of tibial nerve in cubital fossa. EMG abnormalities indicating S1 radiculopathy were followed by H or F wave latencies abnormality in 63% of patients. The rest of 37% of patients of these group showed mild EMG abnormalities followed by normal H or F wave. Normal EMG finding was followed by normal H or F wave. Normal EMG finding was followed by normal H or F wave in 64% of patients. Increased latency of H or F wave without EMG abnormalities in gastrocnemius muscle was present in 36% of patients. The results of this study have proved that measurements of H of F latencies provide the objective evidence of S1 radiculopathy, presenting with the unilateral increase of latency or the absence of response. Abnormal H response latencies without EMG abnormality confirm the condition of sensory root affection only. Mild radicular affection in S1 distribution presented from early beginning or following recovery, was accompanied by normal H or F response, and therefore this test has prognostic value for the course of disorder. PMID- 1883923 TI - Epileptic seizures as a symptom of various neurological diseases. AB - The authors evaluate the most frequent causes of seizures in 562 patients admitted at the emergency out-patient ward because of fits. 194 patients were admitted because of the first occurrence of seizures, in 12 of them the first manifestation was status epilepticus of the generalized (8), or focal type (4). The commonest causes of seizures were alcoholism (82), disturbances of the brain blood flow (74), posttraumatic states (20), brain tumor (4), or encephalopathies. In 11 patients the cause of seizures was not found. Besides the causes, the authors stressed the most frequent type of seizures, as well as therapeutic measures. They pointed out that in alcoholism generalized seizures, and grand mal status were the commonest expression of seizures. The same was found in patients with posttraumatic seizures, but they mostly suffered single attacks, and the same in encephalopathies. In patients with vascular lesions focal seizures were not rare. The antiepileptic therapy is not applied in the first occurrence of convulsions, therapy is causal, linked primarily to basic etiopathogenic mechanism responsible for triggering seizures. PMID- 1883924 TI - [Terminology for functional diagnosis and therapy]. PMID- 1883925 TI - [Functional anterior arrangement as a prosthetic requirement]. PMID- 1883926 TI - [Hydrodynamic in vitro comparison of a new artificial heart valve with the Bjork Shiley valve (standard)]. AB - Measurements performed to compare a newly developed tilting disc valve with the Bjork-Shiley valve included velocity profiles downstream of the heart valves, valve-induced flow turbulence and pressure drop across the opened valves. The velocity profiles measured with pulsed Doppler ultrasound are similar, although they do not permit a quantitative comparison of the valves. The interpretation of the 90 degrees-component of Doppler signals as a measure of the turbulence permits a quantitative comparison without the need for extensive measurements. However, only large vortices are recorded, so that our turbulent shear stresses are lower than these reported in the literature. The pressure drop across the opened valve is a measure of the energy loss, and important parameters for the valve can be derived from it. The pressure drop is dependent on the test conditions, and is therefore not a characteristic constant of the valve. The transformation of the power law Q = C delta P beta into a relation between Re- and Eu-number gives a nondimensional similarity number that is characteristic for tilting disc valves. Its verification requires more investigations, involving variation of valve size and the viscosity of the test fluid. PMID- 1883927 TI - [A two-stage regulatory system for pressure-constant perfusion of coronary vessels]. AB - This paper describes a double-loop servo-controlled pump system for the constant pressure perfusion of a coronary artery. Due to the transient nature of changes in coronary vasomotor tone, such a perfusion system must have a fast regulatory response. In the first stage, a servo-controlled pump primes a windkessel having a volume of 35 ml with blood. The pumping rate is electronically controlled to maintain a constant pressure within the windkessel max. 700 mmHg. The maximal flow rate is 300 ml/min. To reduce the high pressure in the windkessel to the desired coronary perfusion pressure, a variable flow resistance, comprising a clamped thin-walled silicone tube, is provided in the output line of the system. A fast servo-motor drives the clamp and is controlled by an electronic regulator, using a second feedback loop from the pressure signal measured at the tip of the perfusion cannula. The system stabilizes the coronary perfusion pressure within 300 ms. An additional modulation of the setpoint signal in synchrony with the cardiac cycle improves the phasic pattern of the blood flow, and thus prevents changes in transmural blood flow distribution. The dead volume of the overall system is about 60 ml. Hemolysis caused by this system during five hours of perfusion in vivo is negligible. PMID- 1883928 TI - Geometry of varicose veins segments. AB - The geometry of varicose vein segments, chosen from macroscopically normal as well as unmistakable dilated (bulbous) sites of the vessels, were studied in specimens obtained from stripping operations. Geometrical aspects (valves, dilatations) were studied on the vein slit open in axial direction and geometrical parameters (mean diameter, wall thickness) were measured on 3 sets of strips cut in circumferential direction with special reference to their location to the valves. In normal segments the vein is enlarged immediately proximal to the valves. In contrast to this, the bulbous and assymetric protrusions found in the diseased segments lie just below the valves, that is upstream. Values of diameters, wall thickness and wall thickness to diameter ratios are plotted as mean +/- SD in bar graphs. Results indicate that 1. the diameter has a maximum value at the valvular site both in the normal and the diseased segments; the normal diameters are smaller than the corresponding diseased ones. 2. The wall thickness increases from the distal to the proximal site in the normal segments, whereas it displays a minimum value at the valvular site of the bulbous segments. 3. The wall thickness to diameter ratios of both the normal and the pathological segments have a minimum at valvular site, but the normal values are larger than the corresponding pathological values, a behavior which is more apparent in the bulbous enlargements and even evident in the hypertrophied side of the wall opposite to the protrusions. PMID- 1883929 TI - [Digital roentgen analysis as a tool for kinematic studies of the shoulder--a study of radiation dosage]. AB - The radiation exposure during biomechanical investigation of the shoulder joint done with a digital radiography system (Polytron 1000 VR - Siemens) was measured experimentally. Total radiation dose and surface dose were determined by phantom measurements. The radiation exposure per image is about 1/6 to 1/7 of that of a conventional study. The digital radiography system used is thus suitable for kinesiologic studies of large joints in healthy volunteers. PMID- 1883930 TI - Photochemically induced charge separation occurring in bacteriorhodopsin. Detection by time-resolved dielectric loss. AB - Time-resolved dielectric loss (TRDL) measurements are reported for the photochemical excitation of bacteriorhodopsin (bR) in solid films of Halobacterium halobium purple membranes. These measurements provide an independent confirmation for the existence of an important component of charge separation in these membranes after photochemical excitation. The separation of charge is detected by the absorption of microwave energy by the multilayer films of purple membranes in a microwave cavity during flash photolysis experiments. The TRDL method has the advantage of being sensitive to charge separation occurring in both oriented and unoriented films of purple membranes. One disadvantage is that the water content of the samples must be minimized, however, there is some absorbed water present in our electrodeposited solid film samples. To the best of our knowledge, TRDL measurements have not been reported previously for photochemical charge separation in biological membranes. It is significant that an early decay component of TRDL in the 20-microseconds time domain corresponds to the relaxation of the negative charge displacement photocurrent in oriented samples of purple membranes. In addition, a component of charge separation persists during the first several hundred microseconds of the bR photocycle. PMID- 1883931 TI - Organization and dynamics of pyrene and pyrene lipids in intact lipid bilayers. Photo-induced charge transfer processes. AB - The dynamics of fluorescence quenching and the organization of a series of pyrene derivatives anchored in various depths in bilayers of phosphatidylcholine small unilamellar vesicles was studied and compared with their behavior in homogeneous solvent systems. The studies include characterization of the environmental polarity of the pyrene fluorophore based on its vibronic peaks, as well as the interaction with three collisional quenchers: the two membrane-soluble quenchers, diethylaniline and bromobenzene, and the water soluble quencher potassium iodide. The system of diethylaniline-pyrene derivatives in the membrane of phosphatidylcholine vesicles was characterized in detail. The diethylaniline partition coefficient between the lipid bilayers and the buffer is approximately 5,800. Up to a diethylaniline/phospholipid mole ratio of 1:3 the perturbation to membrane structure is minimal so that all photophysical studies were performed below this mole ratio. The quenching reaction, in all cases, was shown to take place in the lipid bilayer interior and the relative quenching efficiencies of the various probe molecules was used to provide information on the distribution of both fluorescent probes and quencher molecules in the lipid bilayer. The quenching efficiency by diethylaniline in the lipid bilayer was found to be essentially independent on the length of the methylene chain of the pyrene moiety. These findings suggest that the quenching process, being a diffusion controlled reaction, is determined by the mobility of the diethylaniline quencher (with an effective diffusion coefficient D approximately 10(-7) cm2 s-1) which appears to be homogeneously distributed throughout the lipid bilayer. The pulsed laser photolysis products of the charge-transfer quenching reaction were examined. No exciplex (excited-complex) formation was observed and the yield of the separated radical ions was shown to be tenfold smaller than in homogenous polar solutions. The decay of the radical ions is considerably faster than the corresponding process in homogenous solutions. Relatively high intersystem crossing yields are observed. The results are explained on the basis of the intrinsic properties of a lipid bilayer, primarily, its rigid spatial organization. It is suggested that such properties favor ion-pair formation over exciplex generation. They also enhance primary geminate recombination of initially formed (solvent-shared) ion pairs. Triplet states are generated via secondary geminate recombination of ion pairs in the membrane interior. The results bear on the general mechanism of electron transfer processes in biomembranes. PMID- 1883932 TI - Binding of peptides with basic residues to membranes containing acidic phospholipids. AB - There are clusters of basic amino acids on many cytoplasmic proteins that bind transiently to membranes (e.g., protein kinase C) as well as on the cytoplasmic domain of many intrinsic membrane proteins (e.g., glycophorin). To explore the possibility that these basic residues bind electrostatically to monovalent acidic lipids, we studied the binding of the peptides Lysn and Argn (n = 1-5) to bilayer membranes containing phosphatidylserine (PS) or phosphatidylglycerol (PG). We made electrophoretic mobility measurements using multilamellar vesicles, fluorescence and equilibrium binding measurements using large unilamellar vesicles, and surface potential measurements using monolayers. None of the peptides bound to vesicles formed from the zwitterionic lipid phosphatidylcholine (PC) but all bound to vesicles formed from PC/PS or PC/PG mixtures. None of the peptides exhibited specificity between PS and PG. Each lysine residue that was added to Lys2 decreased by one order of magnitude the concentration of peptide required to reverse the charge on the vesicle; equivalently it increased by one order of magnitude the binding affinity of the peptides for the PS vesicles. The simplest explanation is that each added lysine binds independently to a separate PS with a microscopic association constant of 10 M-1 or a free energy of approximately 1.4 kcal/mol. Similar, but not identical, results were obtained with the Argn peptides. A simple theoretical model combines the Gouy-Chapman theory (which accounts for the nonspecific electrostatic accumulation of the peptides in the aqueous diffuse double layer adjacent to the membrane) with mass action equations (which account for the binding of the peptides to greater than 1 PS). This model can account qualitatively for the dependence of binding on both the number of basic residues in the peptides and the mole fraction of PS in the membrane. PMID- 1883933 TI - Peptides that mimic the pseudosubstrate region of protein kinase C bind to acidic lipids in membranes. AB - The cytoplasmic form of protein kinase C (PKC) is inactive, probably because the pseudosubstrate region in its regulatory domain blocks the substrate-binding site in its kinase domain. Calcium ions cause a translocation to the membrane: maximum activation requires a negative lipid such as phosphatidylserine (PS) and the neutral lipid diacylglycerol (DAG) but the mechanism by which PS and DAG activate PKC is unknown. Pseudosubstrate region 19-36 of PKC-beta has six basic and one acidic amino acids and region 19-29 has five basic and no acidic amino acids. Since any binding of basic residues in the pseudosubstrate region to acidic lipids in the membrane should stabilize the active form of PKC, we studied how peptides with amino acids equivalent to residues 19-36 and 19-29 of PKC-beta bound to phospholipid vesicles. We made equilibrium dialysis, filtration, and electrophoretic mobility measurements. The fraction of bound peptide is a steep sigmoidal function of the mol fraction of negative lipid in the membrane, as predicted from a simple theoretical model that assumes the basic residues provide identical independent binding sites. The proportionality constant between the number of bound peptides/area and the concentration of peptide in the bulk aqueous phase is 1 micron for a membrane with 25% negative lipid formed in 0.1 M KCl. Equivalently, the association constant of the peptide with the membrane is 10(4) M-1, or the net binding energy is 6 kcal/mol. Thus the interaction of basic residues in the pseudosubstrate region with acidic lipids in the membrane could provide 6 kcal/mol free energy towards stabilizing the active form of PKC. PMID- 1883935 TI - Effect of temperature on the myoglobin-facilitated transport of oxygen in skeletal muscle. AB - An analysis of thermal effects on the facilitative transport of oxygen in skeletal muscle fibers is presented. Steady-state mass and energy transport balances are written and solved analytically or numerically using a finite difference procedure. It is shown that no significant spatial thermal gradients exist due to internal reactions or bulk conduction effects across a muscle fiber. At typical muscle conditions, it is predicted that increased global temperature reduces the fraction of oxygenated myoglobin, increases local oxygen concentrations, and increases the percentage of oxygen flux attributed to oxy myoglobin. The maximum supportable oxygen consumption rate, mO2max, is defined as the highest consumption rate sustainable without developing anoxic regions at the center of the fiber. By considering only temperature sensitive effects within fibers, mO2max is found to increase slightly with temperature at low temperatures. This increase is due to thermal effects on the diffusion coefficients as opposed to effects associated with the kinetics of the myoglobin oxygen reaction. If the simulations include the temperature effect associated with oxygen solubility in blood plasma, mO2max decreases with temperature. A sensitivity analysis was performed by varying the values of relevant parameters. The maximum consumption rate was least affected by parameters associated with the kinetic and equilibrium constants and most affected by the diffusion coefficients and the concentration of myoglobin. PMID- 1883934 TI - Mathematical model for the effects of adhesion and mechanics on cell migration speed. AB - Migration of mammalian blood and tissue cells over adhesive surfaces is apparently mediated by specific reversible reactions between cell membrane adhesion receptors and complementary ligands attached to the substratum. Although in a number of systems these receptors and ligand molecules have been isolated and identified, a theory capable of predicting the effects of their properties on cell migration behavior currently does not exist. We present a simple mathematical model for elucidating the dependence of cell speed on adhesion receptor/ligand binding and cell mechanical properties. Our model can be applied to propose answers to questions such as: does an optimal adhesiveness exist for cell movement? How might changes in receptor and ligand density and/or affinity affect the rate of migration? Can cell rheological properties influence movement speed? This model incorporates cytoskeletal force generation, cell polarization, and dynamic adhesion as requirements for persistent cell movement. A critical feature is the proposed existence of an asymmetry in some cell adhesion-receptor property, correlated with cell polarity. We consider two major alternative mechanisms underlying this asymmetry: (a) a spatial distribution of adhesion receptor number due to polarized endocytic trafficking and (b) a spatial variation in adhesion-receptor/ligand bond strength. Applying a viscoelastic solid model for cell mechanics allows us to represent one-dimensional locomotion with a system of differential equations describing cell deformation and displacement along with adhesion-receptor dynamics. In this paper, we solve these equations under the simplifying assumption that receptor dynamics are at a quasi steady state relative to cell locomotion. Thus, our results are strictly valid for sufficiently slow cell movement, as typically observed for tissue cells such as fibroblasts. Numerical examples relevant to experimental systems are provided. Our results predict how cell speed might vary with intracellular contractile force, cell rheology, receptor/ligand kinetics, and receptor/ligand number densities. A biphasic dependence is shown to be possible with respect to some of the system parameters, with position of the maxima essentially governed by a balance between transmitted contractile force and adhesiveness. We demonstrate that predictions for the two alternative asymmetry mechanisms can be distinguished and could be experimentally tested using cell populations possessing different adhesion-receptor numbers. PMID- 1883936 TI - Effects of individual genetic substitutions of arginine residues on the deprotonation and reprotonation kinetics of the Schiff base during the bacteriorhodopsin photocycle. AB - The rates are determined for the deprotonation and reprotonation of the protonated Schiff base (PSB) as well as of formation and decay of the UV transient in the photocycle of seven bacteriorhodopsin (bR) mutants in which Arg 7, 82, 164, 175, 225, or 227 are replaced by glutamine and Arg-134 by cysteine. The results show that all these mutations increase the rate of deprotonation of the PSB compared to ebR, (wild-type bacteriorhodopsin expressed in Escherichia coli) greatly increase the rate of the reprotonation of the SB (Schiff base) in the case of the Arg-164 and Arg-175 mutations and dramatically decrease this rate in the case of the Arg-227 mutation. Temperature studies on the latter mutant suggest that the observed change in its rate of reprotonation is due to large decrease in the energy and entropy of activation, similar to those observed for Asp-96 mutations (Miller, A. and D. Orsterhelt. 1990. Biochim. Biophys. Acta. 1020:57-64). These results suggest that the reprotonation process is changed to a proton diffusion-controlled mechanism in the Arg-227 mutant due to a change in the structure of the proton channel. The absorption intensity ratio (AUV/AMslow) of each arginine mutant relative to that of ebR is found to be similar to that for native purple membrane (PM) except for the Arg-227 mutant where it is greatly reduced, and for the Arg-82 mutant where it is not observed, suggesting that both Arg-227 and Arg-82 residues somehow play roles in inducing the UV transient absorption. All the above results are discussed in terms of the model for the structure of bR proposed by Henderson, R., J.M. Baldwin, T.A. Ceska, F. Zemlin, E. Beckmann, and K.H. Downing. (1990. J. Mol. Biol. 213:899-929). PMID- 1883937 TI - Quantitation of lipid phases in phospholipid vesicles by the generalized polarization of Laurdan fluorescence. AB - The sensitivity of Laurdan (6-dodecanoyl-2-dimethylaminonaphthalene) excitation and emission spectra to the physical state of the membrane arises from dipolar relaxation processes in the membrane region surrounding the Laurdan molecule. Experiments performed using phospholipid vesicles composed of phospholipids with different polar head groups show that this part of the molecule is not responsible for the observed effects. Also, pH titration in the range from pH 4 to 10 shows that the spectral variations are independent of the charge of the polar head. A two-state model of dipolar relaxation is used to qualitatively explain the behavior of Laurdan. It is concluded that the presence of water molecules in the phospholipid matrix are responsible for the spectral properties of Laurdan in the gel phase. In the liquid crystalline phase there is a relaxation process that we attribute to water molecules that can reorientate during the few nanoseconds of the excited state lifetime. The quantitation of lipid phases is obtained using generalized polarization which, after proper choice of excitation and emission wavelengths, satisfies a simple addition rule. PMID- 1883938 TI - Blockade of cardiac sarcoplasmic reticulum K+ channel by Ca2+: two-binding-site model of blockade. AB - Potassium countercurrent through the SR K+ channel plays an important role in Ca2+ release from the SR. To see if Ca2+ regulates the channel, we incorporated canine cardiac SR K+ channel into lipid bilayers. Calcium ions present in either the SR lumenal (trans) or cytoplasmic (cis) side blocked the cardiac SR K+ channel in a voltage-dependent manner. When Ca2+ was present on both sides, however, the block appeared to be voltage independent. A two-binding site model of blockade by an impermeant divalent cation (Ca2+) can explain this apparent contradiction. Estimates of SR Ca2+ concentration suggest that under physiological conditions the cardiac SR K+ channel is partially blocked by Ca2+ ions present in the lumen of the SR. The reduction in lumenal [Ca2+] during Ca2+ release could increase K+ conductance. PMID- 1883939 TI - Effect of pH buffer molecules on the light-induced currents from oriented purple membrane. AB - The effect of pH buffers on the microsecond photocurrent component, B2, of oriented purple membranes has been studied. We found that under low salt conditions (less than 10 mM monovalent cationic salt) pH buffers can dramatically alter the waveform of the B2 component. The effect is induced by the protonation process of the buffer molecules by protons expelled from the membrane. These effects can be classified according to the charge transition upon protonation of the buffer. Buffers that carry two positive charges in their protonated form add a negative current component (N component) to B2. Almost all of the other buffers add a positive current component (P component) to B2, which is essentially a mirror image of the N component. Buffers with a pK less than 5.5 have only a small positive buffer component. The pH dependence of the buffer effect is closely related to the pK of the buffer; it requires that the buffer be in its unprotonated form. The rise time of the buffer component increases with the concentration of the buffer molecules. All the buffer effects can be inhibited by the addition of 5 mM of a divalent cation such as Ca2+. Reducing the surface potential slows down the N component but accelerates the P component without affecting the amplitude of the buffer effect significantly. Many of the buffer effects can be explained if we assume that upon protonation of the buffer by a proton expelled from the membrane by light, the buffer molecules move toward the membrane. This backward movement of buffer molecules forms a counter current very similar to that due to cations discussed in Liu, S. Y., R. Govindjee, and T. G. Ebrey. (1990. Biophys. J. 57:951-963). PMID- 1883940 TI - Vibrational spectroscopy of excited electronic states in carotenoids in vivo. Picosecond time-resolved resonance Raman scattering. AB - The vibrational spectroscopy and population dynamics of excited singlet (2(1)Ag), excited triplet (3B u), and the ground (1Ag) electronic states of carotenoids in chromatophores of Chromatium vinosum (mainly spirilloxanthin and rhodopin) and of the same carotenoids in benzene solutions are examined by picosecond time resolved resonance Raman scattering. Coherent Stokes Raman scattering from the ground states of carotenoids in chromatophores also is observed. Resonance Raman spectra of in vitro rhodopin and spirilloxanthin when compared with in vivo data demonstrate that scattering from spirilloxanthin dominates the in vivo spectrum. Comparisons of the time-dependent intensities of 2(1)Ag and 1Ag resonance Raman bands from both in vitro and in vivo carotenoids suggest that vibrationally excited levels in 1Ag are populated directly by the decay of the 2(1)Ag state and that these levels relax into a thermalized distribution in less than 50 ps. The appearance of asymmetrically broadened, ground-state resonance Raman bands supports this conclusion. Formation of the 3Bu state is observed for carotenoids in chromatophores, but not for in vitro spirilloxanthin indicating that the 3Bu state is formed by fission processes originating from the spatial organization of pigments within chromatophores. The rate at which the intensities of 2(1)Ag resonance Raman bands decay is faster for the carotenoids in vivo than for those in vitro thereby indicating that additional relaxation channels (e.g., energy transfer to bacteriochlorophylls) are present in the chromatophore. The similarity of the in vivo and in vitro 2(1)Ag resonance Raman spectra shows that no significant modifications in the vibronic coupling has been caused by the chromatophore environment. PMID- 1883941 TI - Molecular dynamics studies of the interface between a model membrane and an aqueous solution. AB - Molecular Dynamics (MD) computer simulation studies are reported for a system consisting of two model membranes in contact with an aqueous solution. The influence of the membrane on the adjacent liquid is of main interest in the present study. It is therefore attempted to make the system sufficiently large to encompass the entire region between bulk liquid and the membranes. The latter are modeled by two-dimensional arrays of COO- groups with rotational and translational degrees of freedom. The water molecules are represented by the well tested TIP4P model. The intermolecular potentials are parametrized in terms of Coulomb interactions between partial charges on the molecular frames and empirical, mostly Lennard-Jones (12-6), interactions centered at the atomic positions. A strong layering of the liquid accompanied by an increase in average water density is found in the vicinity of the membrane. The structural perturbation reaches approximately 8 A into the liquid. We discuss the static structure in these layers in terms of atom-atom distance distribution functions and study the average orientation of the water molecule dipoles with respect to the membrane. From the distribution of the ions, we find that less than 50% of the surface charge of the membrane is neutralized by Na+ ions in the first layer above the membrane. A simplified model of the adsorption site of the ion on the membrane is developed from the distance distributions. Finally the hydration of the Na+ in the first adsorbed layer is discussed. PMID- 1883942 TI - Ultrafast infrared spectroscopy of bacteriorhodopsin. AB - Picosecond infrared spectroscopy is developed and used for the first time to study the dynamics of photoexcited bacteriorhodopsin (BR). Both spectral and time resolved data are obtained. The results open an entirely new approach to investigations of the BR photocycle. The infrared difference spectrum (K minus BR570) recorded at ambient temperature between 1,560 and 1,700 cm-1 is not identical with the spectrum reported for a frozen sample. Three bands of the K state at 1,622, 1,610, and 1,580 cm-1 and the bleaching at 1,637 cm-1 (C = NH stretch) are seen. These new spectral lines appear in less than 10 ps. PMID- 1883943 TI - Cross-bridge cycling theories and high-speed lengthening behavior in frog muscle. PMID- 1883944 TI - Calcium binding by phosphatidylserine headgroups. Deuterium NMR study. AB - The binding of calcium to headgroup deuterated 1-palmitoyl, 2-oleoyl-sn-glycero-3 phosphoserine (POPS) was investigated by using deuterium magnetic resonance in pure POPS membranes and in mixed 1-palmitoyl, 2-oleoyl-sn-glycero-3 phosphocholine (POPC)/POPS 5:1 (m:m) bilayers. Addition of CaCl2 to pure POPS bilayers led to two component spectra attributed, respectively, to liquid crystallin POPS (less than 15 kHz) and POPS molecules in the calcium-induced dehydrated phase (cochleate) (approximately 120 kHz). The liquid-crystalline component has nearly disappeared at a Ca2+ to POPS ratio of 0.5, indicating that, under such conditions, most of the POPS molecules are in the precipitated cochleate phase. After dilution of the POPS molecules in zwitterionic POPC membranes (POPC/POPS 5:1 m:m), single component spectra characteristic of POPS in the liquid-crystalline state were observed in the presence of Molar concentrations of calcium ions (Ca2+ to POPS ratio greater than 50), showing that the amount of dehydrated cochleate PS-Ca2+ phase, if any, was low (less than 5%) under such conditions. Deuterium NMR data obtained in the 15-50 degrees C temperature range with the mixed PC/PS membranes, either in the absence or the presence of Ca2+ ions, indicate that the serine headgroup undergoes a temperature induced conformational change, independent of the presence of Ca2+. This is discussed in relation to other headgroup perturbations such as that observed upon change of the membrane surface charge density. PMID- 1883945 TI - Model of platelet transport in flowing blood with drift and diffusion terms. AB - A drift term is added to the convective diffusion equation for platelet transport so that situations with near-wall excesses of platelets can be described. The mathematical relationship between the drift and the fully developed, steady-state platelet concentration profile is shown and a functional form of the drift that leads to concentration profiles similar to experimentally determined profiles is provided. The transport equation is numerically integrated to determine concentration profiles in the developing region of a tube flow. With the approximate drift function and typical values of augmented diffusion constant, the calculated concentration profiles have near-wall excesses that mimic experimental results, thus implying the extended equation is a valid description of rheological events. Stochastic differential equations that are equivalent to the convective diffusion transport equation are shown, and simulations with them are used to illustrate the impact of the drift term on platelet concentration profiles during deposition in a tube flow. PMID- 1883947 TI - Reduction of the in vitro hemolytic activity of soybean lecithin liposomes by treatment with a block copolymer. AB - The in vitro hemolytic activity of liposomes made of soybean L-alpha-lecithin towards diluted (0.0086 v/v) human erythrocytes was used to investigate the effect of surface coating on the interaction of liposomes with cells. The increase in apparent volume of the block copolymer of ethylene glycol and propylene glycol, Pluronic F-127, in the presence of liposomes supports the hypothesis of either adsorption or penetration of the copolymer at the surface of the liposomes. When the liposomes are pre-incubated with Pluronic F-127, their lytic activity towards fresh erythrocytes is significantly reduced while it remains unchanged towards erythrocytes aged in vitro. It is also found that aging the liposomes has little effect on their lytic activity while aging of the erythrocytes makes them more fragile towards the liposomes. The results are discussed in terms of steric hindrance. PMID- 1883946 TI - Dramatic in situ conformational dynamics of the transmembrane protein bacteriorhodopsin. AB - The conformational dynamic capabilities of the in situ bacteriorhodopsin (bR) can be studied by determination of the changes of the bR net helical segmental tilt angle (the angle between the polypeptide segments and the membrane normal) induced by various perturbations of the purple membrane (PM). The analysis of the far-UV oriented circular dichroism (CD) of the PM provides one means of achieving this. Previous CD studies have indicated that the tilt angle can change from approximately 10 degrees to 39 degrees depending on the perturbants used with no changes in the secondary structure of the bR. A recent study has indicated that the bleaching-induced tilt angle can be enhanced from approximately 24 degrees to 39 degrees by cross-linkage and papain-digestion perturbations which by themselves do not alter the tilt angle. To add further credence, this study has been repeated using midinfrared (IR) linear dichroic spectral analysis. In contrast to the CD method, analysis by the IR method depends on the orientation of the amide plane of the helix assumed. Excellent consistency is achieved between the two methods only when it is assumed that the structural characteristics of the alpha-helices of the bR are equally alpha I and alpha II in nature. Furthermore, the analysis of the IR data becomes essentially independent of the three amide transitions utilized. The net tilt angle of segments completely randomized relative to the incident light must be 54.736 in view of helix symmetry. A value of 54.735 degrees +/- 0.001 degree was achieved by the IR method for the ethanol-treated PM film, establishing this kind of film as an ideal random state standard and demonstrating the accuracy potential of the IR method. PMID- 1883948 TI - Binding of Hg(II) to poly(dA): poly(dT) and its component single strands. AB - Mercuric binding studies at pH 10 revealed that poly(dA): poly(dT) exhibits a more dramatic absorption spectral alteration than the alternating polymer poly(dA dT):poly(dA-dT) and induces a unique intense positive CD band at 296 nm during the spectral titrations. Comparative studies with its component single strands suggest that the spectral alterations exhibited by poly(dA): poly(dT) are consistent with a binding model in which the mercuric ions initially bind to thymines and cause the eventual strand separation of the duplex, with subsequent high cooperative binding to the poly(dA) strands. This interpretation is supported by the binding isotherms indicating much stronger mercuric binding to poly(dT) than to poly(dA), with saturation binding densities of 1 Hg(II) per 2 bases and 1 Hg(II) per base, respectively, and very high binding cooperativity for poly(dA). Striking spectral alterations are exhibited by the mercuric binding to poly(dA), likely the consequence of binding to the amino group of dA in an alkaline solution. The mononucleoside dA exhibits minor spectral alterations upon similar mercuric chloride additions whereas the dinucleoside monophosphate d(AA) exhibits significant spectral changes, albeit less pronounced than those of poly(dA). Some sequence effects on the mercuric binding are observed in the dinucleotide studies. Our CD results on the mercuric binding to polynucleotides do not support the contention of (psi)-type condensed complex formation. PMID- 1883949 TI - Spectrofluorimetric studies on C-terminal 34 kDa fragment of caldesmon. AB - Analysis of the tryptophan fluorescence emission spectra of caldesmon and its 34 kDa C-terminal fragment indicates that all tryptophan residues are located on the surface of the molecule, accessible to solvent. All three tryptophan residues of the 34 kDa fragment and four of the five tryptophan residues of intact protein are accessible to free water, whereas one located in the N-terminal region of molecule is accessible only to bound water molecules. The temperature dependence of the fluorescence parameters indicates higher thermal stability of the 34 kDa fragment than the whole caldesmon molecule. The interaction of the 34 kDa fragment of caldesmon (like that of the intact molecule) with calmodulin is accompanied by a blue shift of the fluorescence emission maximum and an increase in the relative quantum yield. Computer-calculated binding constants show that the binding of calmodulin to the 34 kDa fragment (K = 2.5 x 10(5) M-1) is of two orders of magnitude weaker than that to intact caldesmon (K = 1.4 x 10(7) M-1). The interaction with tropomyosin results in a blue shift of the spectrum of the 34 kDa fragment, yet there is no effect on the spectrum of intact caldesmon. Binding constants of tropomyosin to caldesmon (K = 3.8 x 10(5) M-1) and its 34 kDa fragment (K = 2.3 x 10(5) M-1) are similar. Binding of calmodulin to caldesmon and to the 34 kDa fragment affects their interaction with tropomyosin. PMID- 1883950 TI - The effects of lithium, rubidium, cesium and magnesium ions on the close packing of persistence-length DNA fragments. AB - By application of scaled particle theory to persistence-length DNA fragments in sedimentation-equilibrium at speeds high enough to maintain close packing, the range of interhelical electrostatic repulsion was evaluated with LiCl, RbCl, CsCl, and MgCl2 as supporting electrolytes. Analysis of the data in terms of the Zimm cluster function confirmed that the net interaction between helices is purely repulsive in all cases. At constant ionic strength the electrostatic radius of the rod-like DNA decreases as the counterion changes from Li+ to Rb+ to Cs+. In contrast to univalent counterions, electrostatic radius increases with Mg2+ concentration, except at very low (mM) MgCl2 concentrations. All solutions undergo a reversible transition to a turbid, optically anisotropic phase at a slightly salt-dependent, critical DNA concentration, as observed previously for NaDNA. PMID- 1883951 TI - Interleukin-6 administration has no acute hemodynamic or hematologic effect in the dog. AB - To investigate the possible hemodynamic effects of interleukin-6 (IL-6), a single dose of 15 mcg/kg of recombinant IL-6 isolated from Escherichia coli was injected intravenously in six pentobarbital-anesthetized dogs. After 30 min, saline infusion was performed to maintain the pulmonary artery balloon-occluded pressure at baseline level. The animals were observed for up to 5 hours. No other hemodynamic alteration was observed than a gradual decline in cardiac output attributed to anesthesia. Hematologic variables, blood glucose, and total serum proteins were also constant. IL-6 levels were markedly elevated in the blood, but no tumor necrosis factor activity was detected. Thus a primary role for IL-6 in the early cardiovascular alterations associated with septic shock seems unlikely. PMID- 1883952 TI - Is fatal pancreatitis a consequence of excessive leukocyte stimulation? The role of tumor necrosis factor alpha. AB - This study examines the possible role of excessive leukocyte stimulation in the pathogenesis of acute pancreatitis. Levels of tumor necrosis factor alpha (TNF alpha) and elastase-alpha 1 proteinase inhibitor (E-alpha 1PI) have been measured as markers of macrophage and neutrophil activation, respectively, in serial plasma samples from 27 patients with acute pancreatitis. Levels of TNF-alpha did not support the possibility of excessive macrophage activation, but raised levels of E-alpha 1PI in patients with either the mild or severe form of the illness indicated the activation of neutrophils. Whether this is a consequence of the illness or is a contributory factor in the pathogenesis is not clear. PMID- 1883953 TI - Chemotactic potency of recombinant human neutrophil attractant/activation protein 1 (interleukin-8) for polymorphonuclear leukocytes of different species. AB - In order to establish the species cross-reactivity of the human neutrophil attractant/activation protein-1 (interleukin-8, NAP-1/IL-8) and find which experimental species are responsive to the human cytokine, blood polymorphonuclear leukocytes (PNMLs) were isolated from chicken, dog, goat, guinea-pig, monkey, mouse, pig, rabbit, and rat and their in vitro migration in response to this cytokine was investigated. PMNLs from all of the tested species migrated in response to recombinant human NAP-1/IL-8 (rhNAP-1/IL-8). The potency of rhNAP-1/IL-8 for the PMNLs of different species varied and was considerably lower than its potency for human cells. The morphological study combined with the leukocyte enumeration in the intradermal rhNAP-1/IL-8 injection sites established an in vivo proinflammatory potency of rhNAP-1/IL-8 for rabbit and rat that was comparable to the observed in vitro chemotactic potency of rhNAP-1/IL-8 for neutrophils of these species. PMID- 1883954 TI - Thymus-replacing activity from the metamorphic spleen of Xenopus laevis. AB - Anuran metamorphosis offers an interesting vertebrate immunological paradigm, for adult cells that arise within the immunocompetent larval body are MHC Class I disparate from those of the larva. The animals, in order to avoid immune self destruction during this transition period, are made unresponsive to these modified-self cells by an impairment of T-cell functions. However, it remains to be discovered how an animal with compromised T-cell functions can protect itself from those environmental pathogens protection from which is thymus dependent. During metamorphosis, larval and adult immunocytes capable of reacting to each other coexist within the animal. Their interaction might stimulate the secretion of a cytokine capable of circumventing T-cell functions by acting directly on B cells. Here, we report that such an activity is released in vitro by metamorphic and not by adult splenocyte suspensions. This activity will amplify in vitro anti hapten responses by immunized, but not carrier-primed, adult splenocytes. The activity is unaffected by dexamethasone and, since it will amplify anti-hapten responses in T-cell-depleted immunized adult splenocyte suspensions, the antibody producing (B) cell population may be affected directly. Two radiolabeled protein peaks of 65 kD and 40 kD were obtained by SDS-PAGE analysis from secreting, metamorphosing, but not from adult, splenocytes. PMID- 1883955 TI - Establishment of a novel factor-dependent myeloid cell line from primary cultures of mouse bone marrow. AB - We describe here a novel myelomonocytic cell line (OTT1) obtained from primary cultures of mouse bone marrow cells infected with a retroviral vector carrying the mouse interleukin (IL)-1 alpha gene. OTT1 cells are dependent for their survival and proliferation on IL-3, granulocyte-macrophage colony-stimulating factor (GM-CSF) or, unexpectedly, IL-5. Despite their IL-5 dependency, OTT1 cells form colonies showing predominantly monocyte maturation when plated in methylcellulose. It is suggested that constitutive expression of the exogenous IL 1 alpha gene may predispose to a monocytic phenotype. OTT1 cells should be a useful experimental model to investigate the molecular mechanisms of IL-5 signal transduction and the possible interrelationships between this signal pathway and those utilized by IL-3 and GM-CSF. PMID- 1883956 TI - Detecting cytokine production at the single-cell level. AB - Cytokines are versatile mediators of intercellular communication. Their functional diversity has aroused considerable interest and prompted the rapid development of a number of techniques for their detection and measurement. However, conventional cytokine assays measure only their bulk release by large numbers of cells and give no indication of the identity or frequency of producer cells. Here, the advantages and disadvantages of a relatively new approach to detect cytokine production by single cells are reviewed. PMID- 1883957 TI - Hypoxia increases production of interleukin-1 and tumor necrosis factor by human mononuclear cells. AB - Exposure to hypoxia (PO2 = 9 +/- 1 torr) increased human peripheral blood mononuclear cell production and secretion of interleukin-1 (IL-1)alpha, IL-1 beta, and tumor necrosis factor (TNF) percent of control = 190% for IL-1 alpha, p = 0.014; 219% for IL-1 beta, p = 0.014; and 243% for TNF, p = 0.037) following treatment with endotoxin (1 ng/ml). Hypoxia potentiated the increased production of these inflammatory cytokines at subthreshold levels of endotoxin with potentiation increasing at lower O2 concentrations. Hypoxia also increased cytokine production induced by the tumor promoter phorbol myristate acetate, suggesting a generalized biologic response. We conclude that hypoxia increases IL 1 and TNF production and speculate that this mechanism aggravates a variety of pathologic conditions involving endotoxin such as adult respiratory distress syndrome (ARDS), multiple organ failure, and septic shock. PMID- 1883958 TI - Fever produced by intrahypothalamic injection of interleukin-1 and interleukin-6. AB - Pure human interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6), both of natural origin, were found to cause fever in rabbits when injected into the PO/AH region of the brain. The threshold dose required for this effect was between 0.4 and 4 U, equivalent to 0.04 to 0.4 ng for IL-1 beta, and around 50 U, equivalent to 0.05 ng for IL-6. From this it was estimated that this area of the brain responds to a local concentration of approximately 1 ng/ml of these cytokines, a level which can easily be reached after intravenous administration of threshold pyrogenic doses of either cytokine. The observation supports the view that fever induced by systemic endogenous production of IL-1 and IL-6 is due to a direct effect on the thermoregulatory center and may not require production of mediators, such as prostaglandins, at sites distant from the center. PMID- 1883959 TI - Fever and acute-phase response induced in rabbits by intravenous and intracerebroventricular injection of interleukin-6. AB - We investigated the effect of human recombinant interleukin-6 (IL-6) on body temperature and acute-phase response, including changes in plasma levels of iron, zinc, copper, and fibrinogen and in circulating leukocyte count. The intravenous (IV) injection of IL-6 (2 micrograms/kg) produced a monophasic fever. The intracerebroventricular (ICV) injection of IL-6 produced a dose-dependent fever that developed gradually and remained elevated throughout the 5-h recording period. The IV injection of IL-6 decreased the plasma concentration of iron and zinc and increased the circulating leukocyte count. The ICV injection of IL-6 resulted in similar trace metal and leukocyte changes, and increased plasma levels of fibrinogen. These results show that IL-6 can cause fever when injected IV or ICV and induces some acute-phase responses through its action on peripheral target organs and in the central nervous system. PMID- 1883960 TI - Marked cell-type-specific differences in glycosylation of human interleukin-6. AB - Human interleukin-6 (IL-6) secreted by cytokine- or endotoxin-induced fibroblasts, monocytes, keratinocytes, endometrial stromal cells, and endothelial cells, when analyzed under denaturing and reducing conditions, consists of a set of differentially modified phosphoglycoproteins of molecular mass in the range from 23 to 30 kD (a set of at least three O-glycosylated 23- to 25-kD species and a set of at least three N- and O-glycosylated 28- to 30-kD species). The 23- to 25-kD and 28- to 30-kD fibroblast-derived IL-6 species have been separately purified to homogeneity with the use of a combination of lectin and immunoaffinity chromatography. Glycosidase digestion experiments on such purified preparations confirmed that almost all human fibroblast-derived IL-6 species were O-glycosylated; additionally, the 28- to 30-kD species were N-glycosylated. Amino acid sequencing revealed that the major amino terminus in the fibroblast-derived 23- to 25-kD O-glycosylated IL-6 was at Ala28 whereas the major amino terminus in the 28- to 30-kD N- and O-glycosylated IL-6 was at Val30, suggesting that targeting of newly synthesized IL-6 polypeptides into the two different processing pathways in fibroblasts may be keyed to differences in the signal peptide cleavage site. Unexpectedly, IL-6 "constitutively" secreted by the Epstein-Barr virus (EBV)-infected human and primate (tamarin) B-cell lines designated sfBJAB and sfBT, respectively, consisted of a major apparently unglycosylated 21-kD species and a minor 25-kD N-glycosylated species.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1883961 TI - High-level production of murine interleukin-5 (IL-5) utilizing recombinant baculovirus expression. Purification of the rIL-5 and its use in assessing the biologic role of IL-5 glycosylation. AB - We describe here a recombinant baculovirus expression system useful for high level production of murine recombinant interleukin-5 (rIL-5). In addition, we describe a single-step technique of purification of the rIL-5 from the baculovirus-infected Sf9 cell supernatants, using an anti-IL-5 affinity column. The baculovirus-derived rIL-5 has physical properties and functional activities in various lymphoid cell assays similar to those of natural T cell-derived IL-5 and reacts with anti-IL-5 antibodies. Finally, the rIL-5 is similar to natural T cell-derived IL-5 in manifesting heterogeneous glycosylation; however, glycosylation does not appear to be necessary for biologic function, at least in a lymphoid cell proliferation assay. PMID- 1883962 TI - The processing of interleukin-1 beta studied with antibodies raised against synthetic peptides from the precursor N-terminal region. AB - The exact sequence of events during processing of human interleukin-1 beta (IL-1 beta) and the fate of the N-terminal region are unknown. We have used anti peptide sera specific for the precursor and mature regions of IL-1 beta to study biosynthesis. These were raised against peptides corresponding to amino acids 1 15, 17-32, and 43-54 of the precursor and a peptide corresponding to the C terminal 33 amino acids of mature human IL-1 beta. Antiserum to the mature region peptide immunoprecipitated the 35-kD precursor from cell lysates and 17-kD mature IL-1 beta and a 31-kD protein from the culture supernatants from radiolabeled human peripheral blood monocytes stimulated with lipopolysaccharide (LPS). Antisera to peptides from the precursor region also immunoprecipitated the 35-kD IL-1 beta precursor but not the 31-kD or 17-kD forms. Of the precursor-specific sera, only antiserum to amino acids 1-15 specifically recognized any other proteins; a peptide of 18 kD and a low molecular weight peptide, both of which accumulated in the medium. The 18-kD protein was not recognized by any of the other antisera and is unlikely to be the N-terminal region of the precursor removed during processing. Pulse-chase experiments indicated that the 31-kD protein could be a processing intermediate and also that it was itself an end product along with full-length precursor. Only 17-kD mature IL-1 beta had biological activity. PMID- 1883963 TI - Renal biopsy instrument. PMID- 1883964 TI - Endothelial cell biology in relation to current concepts of vessel wall structure and function. AB - Vascular endothelium is now appreciated to modulate vessel wall structure and function in health and disease. Strategically located between the intravascular space and vessel wall proper, the endothelium has a broad capacity to modify the functional state of adjacent or trafficking cells. Furthermore, recent findings indicate that the endothelium is an interactive tissue capable of responding to numerous mechanical, chemical, and cellular stimuli. The focus of this review will be a discussion of endothelial cell biology in relation to vascular structure and function, with particular emphasis on endothelial modulation of vasomotor tone. It is evident that endothelial cells contribute to the local control of vascular tone by releasing potent vasodilatory mediators, such as endothelium-derived relaxing factor, and vasoconstrictor mediators such as endothelin-1. The endothelium also serves to modify blood-borne signals to which vascular tissues respond. The kidney shares, directly and indirectly, in these events, making this emerging new area a focus of major interest for nephrologists. PMID- 1883965 TI - Metabolic aspects of protection by glycine against hypoxic injury to isolated proximal tubules. AB - To clarify the roles of butyrate and acylglycine formation in hypoxic proximal tubule cell injury and protection by glycine and to test the contribution of iodoacetate-suppressible metabolism to protection, (1) it was determined whether protection by glycine is fully expressed when glucose, lactate, alanine, and butyrate are replaced by alpha-ketoglutarate as the sole substrate for the tubules, (2) butyrate metabolism and acylglycine formation were directly measured in control and hypoxic preparations, and (3) it was assessed whether injury produced by iodoacetate, a potent inhibitor of glycolytic metabolism, is subject to protection by glycine. Susceptibility to hypoxic injury in medium with alpha ketoglutarate as the sole substrate was similar to that seen in medium containing glucose, lactate, alanine, and butyrate. Tubules in alpha-ketoglutarate medium showed high degrees of protection by glycine against injury produced by 30-min of hypoxia, by iodoacetate alone, and by iodoacetate combined with hypoxia. Protection did not require preservation of cell ATP or glutathione. In glucose lactate-alanine-butyrate medium, butyrate, measured by gas chromatography, was rapidly metabolized by oxygenated tubules and fully accounted for basal rates of oxygen consumption. Butyrate utilization stopped during hypoxia. Neither aspect of butyrate metabolism was altered by glycine. Formation of acylglycines was assessed by gas chromatography/mass spectroscopy. In preparations treated with glycine, butyrylglycine was detected under both oxygenated and hypoxic conditions; the quantities, however, were small and no other acylglycines were found. These observations indicate that protective effects of glycine are independent of short-chain acylglycine formation and glycolytic metabolism. PMID- 1883966 TI - Minimal role of xanthine oxidase and oxygen free radicals in rat renal tubular reoxygenation injury. AB - The role of xanthine oxidase and oxygen free radicals in postischemic reperfusion injury in the rat kidney remains controversial. Proximal tubules, the focal segment affected by ischemic renal injury, were isolated in bulk, assayed for xanthine oxidase activity, and subjected to 60 min of anoxia or hypoxia and 60 min of reoxygenation to evaluate the participation of xanthine oxidase and oxygen radicals in proximal tubule reoxygenation injury. The total xanthine oxidase in isolated rat proximal tubules was 1.1 mU/mg of protein, approximately 30% to 40% of the activity found in rat intestine and liver. Lactate dehydrogenase release, an indicator of irreversible cell damage, increased substantially during anoxia (39.8 +/- 2.3 versus 9.8 +/- 1.8% in controls) with an additional 8 to 12% release during reoxygenation. Addition of 0.2 mM allopurinol, a potent xanthine oxidase inhibitor, and dimethylthiourea, a hydroxyl radical scavenger, failed to protect against the reoxygenation lactate dehydrogenase release. Analysis of xanthine oxidase substrate levels after anoxia and flux rates during reoxygenation indicates that hypoxanthine and xanthine concentrations are in a 15 fold excess over the enzyme Km and 0.3 mU/mg of protein of xanthine oxidase activity exists during reoxygenation. Hypoxic tubule suspensions had a minimal lactate dehydrogenase release during hypoxia and failed to demonstrate accelerated injury upon reoxygenation. In conclusion, although xanthine oxidase is present and active during reoxygenation in isolated rat proximal tubules, oxygen radicals did not mediate reoxygenation injury. PMID- 1883967 TI - The effect of high parathyroid hormone levels on the development of aluminum induced osteomalacia in the rat. AB - A relative deficiency of parathyroid hormone (PTH) is generally observed in dialysis patients with aluminum-associated osteomalacia or aplastic bone disease. It has been suggested that high PTH levels may protect against the development of aluminum-associated bone disease. Through the use of a previously established model of aluminum-induced osteomalacia in the rat, the protective effect of PTH was evaluated. Aluminum was administered intraperitoneally at doses of 0, 5, 10, and 20 mg during a 2-day period, and rats were sacrificed 5 and 12 days after aluminum administration. PTH (bovine 1-34) was administered via a subcutaneously implanted Alzet pump at 2 U/h starting 4 days before aluminum administration and continuing until sacrifice. As the aluminum dose was increased to 20 mg, the osteoblast surface and the bone formation rate decreased. PTH supplementation increased the osteoblast surface at all doses of aluminum and increased the bone formation rate at 0 and 5 mg of aluminum. However, even with PTH supplementation, osteoblast surface decreased as the aluminum dose increased. In the absence of PTH supplementation, osteoblast surface was markedly reduced when the serum aluminum concentration was greater than 400 micrograms/liter or stainable trabecular aluminum surface exceeded 15%. When the stainable trabecular aluminum surface was greater than 12%, the bone formation rate was zero even during supplemental PTH administration. A significant correlation was observed between serum aluminum and stainable trabecular aluminum surface (r = 0.80 at 5 days and r = 0.86 at 12 days; P less than 0.001). However, after PTH administration, less stainable trabecular aluminum was present for the same serum aluminum concentration. Both with and without PTH, the slope of the correlation between serum aluminum and stainable trabecular aluminum surface was steeper at 5 days after aluminum administration than at 12 days. In conclusion, for an equivalent aluminum exposure, high PTH levels protected against the development of low turnover aluminum bone disease in the rat. PMID- 1883968 TI - A hereditary model of slowly progressive polycystic kidney disease in the mouse. AB - There are two known forms of hereditary polycystic kidney disease (PKD) in humans. Although both forms initiate early in life, autosomal recessive PKD is rapidly progressive to kidney failure shortly after birth whereas autosomal dominant PKD is slowly progressive, taking many years to end stage. Research in this field has been limited by the availability of suitable animal models of PKD. Recently the C57BL/6J-cpk mouse has been used to study the pathogenesis of rapidly progressive hereditary PKD. The study presented here describes a slowly progressive PKD in the DBA/2-pcy mouse. The disease trait is transmitted in an autosomal recessive pattern and was localized to chromosome 9 through linkage to the dilute coat color and transferrin genes. Whereas some cystic changes were seen in fetal and newborn affected mice, renal enlargement did not develop until after 8 weeks of age and azotemia did not develop until after 18 weeks of age. Renal cysts were identified in all segments of the nephron and collecting duct and progressively enlarged with age. Individual cysts were found to be lined by a single layer of epithelial cells in most areas, with focal polyps and mounds of cells principally in collecting duct cysts. Early stages of cyst formation were associated with some abnormalities of tubular and glomerular basement membranes and accelerated eruption of incisors. Late stages of the disease were characterized by azotemia and chronic renal interstitial inflammatory infiltrates in all affected animals and cerebral vascular aneurysms in a few. We conclude that the DBA/2-pcy mouse has a form of renal cystic disease that appears similar in many respects to that seen in the dominant form of human PKD. PMID- 1883969 TI - A multicenter clinical trial of epoetin beta for anemia of end-stage renal disease. AB - Patients with anemia of end-stage renal disease were studied for 36 weeks to determine efficacy, safety, and long-term benefits of epoetin beta administration. A total of 131 patients participated in the 12-week, double blind, placebo-controlled portion of the multicenter study. For the first 6 weeks (fixed-dose period), patients were randomized to receive 100 U/kg of epoetin beta or placebo thrice weekly; in the second 6 weeks (dose-adjustment period), the dose of epoetin beta ranged from 50 to 150 U/kg thrice weekly. Of the 131 patients who entered the placebo-controlled period, 122 crossed over to a 24-week open-label period, where all patients received active drug and doses of epoetin beta could be individually titrated after the first 6 weeks. One hundred patients completed the 36-week study. In all phases of the study, epoetin beta was shown to produce a consistent, sustained increase in hemoglobin (baseline, 7.1 +/- 0.1 to 10.5 +/- 0.2 g/dL) and hematocrit (baseline, 21.5 to 32.7%), which virtually eliminated the need for packed red blood cell transfusions. Reticulocyte counts rose initially in response to epoetin beta and stabilized at levels higher than baseline throughout the remainder of the study period (baseline, 1.7 to 2.5%). The placebo group showed no change in these parameters during the double-blind period. Similar patterns of response were seen in the original placebo group after crossover to active drug (mean hemoglobin increase, 2.6 +/- 0.5).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1883970 TI - Bubble cells: renal tubular cells in the urinary sediment with characteristics of viability. AB - The urinary sediment was examined by light microscopy in 65 consecutive inpatients with renal insufficiency (not due to pre- or postrenal factors) referred to a nephrology consult service for evaluation. In the 60 patients in whom a single diagnosis was reached, the sediments of 34 (57%) contained an easily recognized cell, which we have called the "bubble cell". These cells were bizarre, large cells with a single nucleus, which appeared to contain one or more fluid-filled vesicles. Bubble cells were most prevalent in the sediment of patients with acute tubular necrosis but were also seen a variety of other renal diseases. In most patients with acute tubular necrosis, the sediment also contained "normal"-appearing renal tubular cells, muddy brown casts, and oval fat bodies which were indistinguishable from those seen in the nephrotic syndrome. By electron microscopy, the bubble cells appeared to be vacuolated renal tubular epithelial cells, which had characteristics of viable cells. Most bubble cells excluded the vital dye Trypan blue, whereas the normal-appearing renal tubular cells were typically strongly positive. It was concluded that bubble cells, often accompanied by oval fat bodies, are commonly present in the sediment of patients with acute tubular necrosis as well as many other types of renal disease. Most cells which would be classified as "normal" renal tubular cells in these sediments are dead. In contrast, the findings suggest that the bubble cell represents an injured but viable renal tubular cell. The frequent finding of oval fat bodies in the same sediments suggests that the oval fat body is also produced by tubular cell injury. PMID- 1883971 TI - Barrett's oesophagus. PMID- 1883972 TI - Disinfection and endoscopy: summary and recommendations. Working party report to the World Congresses of Gastroenterology, Sydney 1990. AB - This working party was convened by the organizers of the World Congresses of Gastroenterology, Sydney 1990. Its remit was to produce a report on disinfection in endoscopy. Endoscopy plays an essential role in the management of gastrointestinal disorders; its benefits far outweigh the occasional complications which arise. Nevertheless, case reports and surveys performed over a 20-year period confirm that endoscopic procedures do occasionally cause cross infection and the current epidemic with human immunodeficiency virus (HIV) has highlighted the potential for more serious disease transmission if suitable precautionary measures are not generally applied in endoscopy practice. Contaminated equipment may cause infection in three ways: transmission of pathogenic organisms from one patient to another, the commonest example being Salmonellosis; transmission of infection such as hepatitis B (HBV) from patient to staff by needle-stick injury; and introduction of opportunistic organisms which colonize endoscopic and ancillary equipment on storage. This may cause focal sepsis or septicaemia, particularly in the immunocompromised, or cholangitis and pancreatic sepsis following endoscopic retrograde cholangiopancreatography (ERCP). These risks can be eliminated by the use of effective cleaning and disinfection techniques, by providing suitable staff training and by paying attention to endoscopy room procedures. Both HBV and HIV are inactivated by all currently accepted disinfecting or sterilizing procedures.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1883973 TI - Disinfection and endoscopy: the clinical risks of infection. PMID- 1883974 TI - Disinfection and endoscopy: microbial considerations. PMID- 1883975 TI - Endoscopic disinfection: practices and recommendations. PMID- 1883976 TI - Disinfection and endoscopy: procedures and staff safety. PMID- 1883977 TI - Cleaning and disinfection of flexible endoscopes and ancillary equipment: use of automatic disinfectors. PMID- 1883978 TI - Recovery of the small intestine in coeliac disease on a gluten-free diet: changes in intestinal permeability, small bowel morphology and T-cell activity. AB - Intestinal permeability was assessed before and 1, 2, 4, 8 and 12 weeks after commencing a gluten-free diet (GFD) in eight coeliac subjects. Intestinal morphology was quantified in six coeliac subjects on a normal diet, six coeliac subjects on a GFD, and 21 normal subjects. T-cell activity was measured in the eight coeliac subjects by soluble interleukin-2 receptor (sIL-2R) concentration (normal less than 477 U/mL). Intestinal permeability was increased 10-fold with a geometric mean value of 0.72 on a normal diet, and decreased to 0.17 at 4 weeks (P = 0.04), to 0.07 at 8 weeks (P = 0.010), and to 0.20 at 12 weeks (P = 0.015) of a GFD. Two of the eight subjects showed a poor response to gluten withdrawal. Quantitative intestinal morphology showed no significant improvement after 3 to 6 months of a GFD. Mean +/- s.d. sIL-2R concentrations in the eight subjects were increased 5-fold higher than control values at 1400 +/- 530 U/mL on a normal diet and decreased to 750 +/- 200 U/mL after 12 weeks of a GFD (P = 0.004). We conclude that intestinal permeability improves rapidly in the majority of coeliac subjects after commencing a GFD, although some abnormal permeability and increased T-cell activity persists. This may be due to varying degrees of gluten ingestion resulting in continued immune activation. PMID- 1883979 TI - Effect of thiamine on glucose utilization in hepatic cirrhosis. AB - Thiamine, an essential co-enzyme, improves glucose utilization. Thiamine hydrochloride (50 mg per capita per day for 30 days), given to 25 patients with liver cirrhosis who had hyperglycaemia, produced a significant reduction (P less than 0.001) in blood glucose levels. It is therefore suggested that thiamine supplements be given to cirrhotics with hyperglycaemia, to improve glucose utilization. PMID- 1883980 TI - Duplex Doppler ultrasound of the ligamentum teres and portal vein: a clinically useful adjunct in the evaluation of patients with known or suspected chronic liver disease or portal hypertension. AB - The prevalence and potential value of the detection of signs of portal hypertension by duplex Doppler ultrasound (DDU) of the ligamentum teres and portal vein in patients with known or suspected chronic liver disease and/or portal hypertension was studied in 136 consecutive patients undergoing clinical assessment including that of liver histopathology. Portal hypertension was considered to be present when any of the following DDU signs, previously demonstrated to be specific for portal hypertension, were present: an enlarged and/or patent para-umbilical vein, portal vein obstruction or hepatofugal flow in the portal vein. Of 123 patients with parenchymal liver disease, eighty-three had cirrhosis and, of these, portal hypertension was detected on DDU criteria in 86% of alcoholic cirrhotics and 67% of non-alcoholic cirrhotics. Of the 42 patients with non-cirrhotic liver disease, 1 of 7 patients with metastatic liver disease and 3 of 5 patients with alcoholic hepatitis had DDU signs of portal hypertension. Thus, in patients with parenchymal liver disease, DDU had a sensitivity of 73%, specificity of 90% and predictive values of 94 and 62% for positive and negative studies respectively for the detection of cirrhosis. In all 14 patients with portal hypertension secondary to vascular occlusive diseases, DDU examination of the ligamentum teres, portal vein and hepatic vein gave an accurate guide to the site of the occluding lesion. The high positive predictive value of DDU and its ability to aid in localizing the site of increased resistance to flow through the liver suggest that DDU of the ligamentum teres and portal vein is a potentially useful non-invasive adjunct in the assessment of patients with suspected or known liver disease or portal hypertension. PMID- 1883981 TI - Fatal amoebic liver abscess: an autopsy study. AB - An autopsy study of 20 cases is presented. The mean age was 32 years (range: 14 45). Four cases (20%) presented with jaundice. Another four (20%) had continuous fever with abdominal pain. Six had loose motions with blood and mucus in the stools. The mean duration of illness was 7.2 days. All cases were thin and emaciated. Liver was grossly enlarged (mean weight: 2680 g). The abscess was single in all cases except one. The right lobe was involved in 15 cases, the left in four and both in one. The average size of abscess was 13 cm. The abscess had ruptured in the abdomen in 3 patients, for which laparotomy was performed. Pulmonary involvement was seen in 3 cases. Colon showed ulceration in half the patients. In 2 cases perforation was also present. No cerebral involvement was present. A number of interesting features emerged from this study. Although amoebic liver abscess is a common disease, its diagnosis can be missed due to unusual presentation. In the present study, diagnosis of viral hepatitis, carcinoma lung, bacillary dysentery and enteric fever with perforation were made, which probably contributed materially to fatal outcome. PMID- 1883983 TI - Colonic inflammation and anti-inflammatory drugs. PMID- 1883982 TI - Immunoglobulin G subclasses of antibodies to hepatitis B core antigen in HBs antigen positive liver diseases. AB - Serum immunoglobulin G (IgG) subclasses of hepatitis B core antibody (anti-HBc) in 54 patients with different types of hepatitis B surface antigen positive (HBsAg+) liver diseases (asymptomatic carrier (ASC), acute hepatitis (AH), chronic hepatitis (CH) and liver cirrhosis (LC)) and 18 normal controls were estimated by enzyme-linked immunosorbent assay (ELISA) using subclass specific anti-human mouse monoclonal antibodies. In 11 cases, the estimations were carried out at both exacerbation and remission stages of chronic active hepatitis (CAH). In 4 cases of CAH, serial observations of anti-HBc IgG subclasses were made according to the clinical course. In 5 cases of CAH, the estimations were carried out at the HBe antigen positive (HBeAg+) stage and after sero-conversion to anti HBe positive (anti-HBe+) stage. In ASC the main anti-HBc IgG subclasses were restricted to one subclass--anti-HBc IgG1. In AH on the other hand, all the subclasses were represented. In CH all the subclasses were detected under different diagnostic conditions but anti-HBc IgG1 was the main subclass. In LC the mean concentration of anti-HBc IgG3 was higher than the concentration of anti HBc IgG1. In exacerbation stages of CAH, the different anti-HBc IgG subclasses had higher concentrations than in remission stages. The concentrations of different anti-HBc IgG subclasses fell just after seroconversion from HBeAg+ stage to anti-HBe+ stage. These data suggest that the estimation of anti-HBc IgG subclasses may be helpful in establishing the diagnosis of different types and stages of HBsAg+ liver diseases. PMID- 1883984 TI - Mechanism of action of isosorbide-5-mononitrate in reducing portal pressure in cirrhotic patients with cirrhosis and portal hypertension. PMID- 1883985 TI - Acquisition of a matching-to-sample task in young and middle-aged male and female rats. AB - Male and female rats were trained in a water-reinforced matching-to-sample task. The rule was acquired more rapidly by the females. After initial training, the retention of the rule was measured when the rats were twelve and 14 months old. The performance of neither group was modified at twelve months, but at 14 months, while no change appeared in the performance of males, females showed a drop in correct responses. Training in a modified device which made the task more difficult induced no changes in performance. Final training (at 18 months) showed the drop in performance in females had persisted. The decline of performance in middle-aged females might be related to the ageing female reproductive system. PMID- 1883986 TI - Stages of recovery during post-traumatic amnesia and subsequent everyday memory deficits. AB - Post-traumatic amnesia (PTA) is the period following brain trauma when patients are unable to acquire and retain information. Nineteen patients with brain injury were assessed for PTA, with a new scale, after they regained consciousness, every 24 h. Patients recovered orientation and their capacity to recognise new information, and finally their ability to recall this information. The longer the duration of PTA, the poorer was performance on an everyday memory test given one month after recovery from PTA. Patients with orthopaedic injuries and without brain injury showed minimal impairment on the PTA scale. The predictive value of the scale (multiple R = 0.88) with respect to subsequent everyday memory performance indicates its usefulness as an index of severity of brain injury. PMID- 1883987 TI - Extracellular ATP elevates cytosolic Ca2+ in cochlear inner hair cells. AB - The local extracellular application of ATP to isolated sensory inner hair cells (IHC) generated a rapid and transient increase in the concentration of cytosolic free Ca2+, peaking within 1 to 5 s. The dose-response curve indicated a half-max stimulation to be 5 microM ATP. The application of the structural derivatives ADP and alpha-beta-methyleneATP did not generate significant Ca2+ response. By contrast, ATP-alpha-S, an agonist for P2z receptor, was fully active in generating Ca2+ responses. In the absence of extracellular free calcium, the ATP induced Ca2+ increase was still observed, indicating that ATP generated the liberation of Ca2+ from internal stores. These results suggest that extracellular ATP, through an activation of P2-purinergic receptors, may have a neuromodulatory role in the cochlear physiology at the level of the IHC. PMID- 1883988 TI - Visual activity in macaque area V4 depends on area 17 input. AB - It is known that some direct projections from the lateral geniculate nucleus terminate in area V4 of the macaque monkey. Retinal information can also bypass area 17 and reach V4 through relays in the superior colliculus and pulvinar. This raises the question whether area V4 is visually responsive in the absence of input from area 17. We tested this possibility by recording in area V4 while inactivating a region of area 17 by cooling. This led to a complete abolition of the visual responses of practically all the neurons whose receptive fields were included in the visual field region coded by the inactivated zone in area 17. In contrast, neurons whose receptive fields were outside this region remained visually responsive. PMID- 1883989 TI - Strongly glucocorticoid receptor immunoreactive neurons in the neonatal rat brain. AB - Brain glucocorticoid receptor (GR) immunoreactivity was studied in the neonatal rat. Already at postnatal days 1-3 strongly GR immunoreactive (IR) neurons were found in the arcuate and paraventricular hypothalamic nuclei. Moderately to strongly GR IR neurons were found in the locus coeruleus and raphe nuclei, while only weakly GR IR neurons were present in the CA1 and CA2 areas of the hippocampus. GR IR increases steadily during the postnatal period reaching adult levels at day 16. Thus, GR may play a role in the maturation of these hypothalamic nuclei and the 5-hydroxytryptamine and noradrenaline neurons, and GR may provide a basis for the ability of stress-induced increases of glucocorticoids to influence distinct brain circuits during postnatal development. PMID- 1883990 TI - Properties of a synaptic vesicle protein binding plasma membranes. AB - Synaptic vesicles contain a protein (agglutinin) which binds cell plasma membranes. The protein activity is titrated measuring the agglutination of rabbit trypsinized-fixed red blood cells induced by serial dilutions of purified vesicles. The protein is highly concentrated in vesicles: the specific activity is 150-fold higher in vesicles compared to the brain homogenate, and 20-fold higher compared to the crude synaptosomal membrane fraction. The binding is specifically inhibited by the four major brain sialoglycosphingolipids, with a higher affinity for polysialo- rather than for monosialoganglioside (GM1) IC50 are 3.9 x 10(-5) M (GT1b), 8.9 x 10(-5) M (GD1a), 2.8 x 10(-4) M (GD1b) and 4.9 x 10(-4) M (GM1). Cells which are not agglutinated by the vesicles (human red blood cells) can be activated by incubation with gangliosides: insertion of the glycolipids in the plasma membranes makes them sensitive to the vesicle haemagglutinin. PMID- 1883991 TI - Functional changes in cultured neurons following transient asphyxia. AB - Functional responses of cultured neurons from rat cortex and hippocampus to transient hypoxia/asphyxia was studied by the measurement of [3H]2-deoxy-D glucose (2DG) specific uptake. Hypoxic insult was induced by incubating the cells in 5% CO2/95% N2 or in 1 mM NaCN-containing culture medium for various periods of time. Cell morphology, lactate dehydrogenase efflux and protein levels were also examined. Twenty-four hours following hypoxia (6 to 8 h in an anaerobic atmosphere or 90 min in the presence of NaCN) 2DG specific transport was significantly enhanced, without morphological alteration. Cell injury was evident three days post-hypoxia, with a significantly reduced rate of cellular metabolism. The data suggest indirectly that postanoxic release of excitatory amino acids may be responsible for 'delayed neuronal death'. PMID- 1883992 TI - Binding of an endosperm-specific nuclear protein to a maize beta-zein gene correlates with zein transcriptional activity. AB - Promoter regions of alpha- and beta-zein genes were analyzed for binding of nuclear proteins from developing endosperm and seedling tissue of maize. Using a band-shift assay, we identified two distinct protein factors, alpha-1 and beta-1, that interacted specifically with alpha- and beta-zein gene promoter regions, respectively. Alpha-1 was present in nuclei from both endosperm and seedling tissue, whereas beta-1 was found only in nuclei from developing endosperm tissue. Mixing of nuclear extracts demonstrated that seedling tissue contained undetectable amounts of beta-1, rather than having an inhibitor for formation of the beta-1/DNA complex. Chemical footprinting analysis localized the beta-1 recognition site to a 22 bp sequence flanked by CCAT and TATA boxes. The apparent molecular mass of beta-1 was determined to be 29 kDa by southwestern blotting. Based on in vitro binding assays, the greatest concentration of the beta-1 in endosperm nuclei is at 16 days after pollination, which coincides with the time of highest transcriptional activity of the beta-zein gene. These results suggest that beta-1 may act as a tissue-specific, trans-acting regulator of the expression of the beta-zein gene in developing maize endosperm. PMID- 1883993 TI - Cloning of the pea cdc2 homologue by efficient immunological screening of PCR products. AB - A homologue of the ubiquitous eukaryotic cell cycle regulatory gene, cdc2, has been cloned from Pisum sativum, the garden pea. A novel immunological strategy was devised and implemented for screening PCR products generated by degenerate oligonucleotide primers. We used PCR to construct a deletion derivative of an Escherichia coli expression plasmid carrying the Schizosaccharomyces pombe cdc2 gene. The deleted segment encoded the domain recognized by monoclonal antibody MAb-J4, a reagent which also detects a single protein in extracts of all plant species we have examined. PCR products, generated by appropriate cdc2 primers, were ligated into new restriction sites flanking the deletion, reconstituting the deleted epitope. This strategy, first validated on a cloned yeast cdc2 template as control, was applied to the highly efficient cloning of a cDNA segment comprising 60% of the pea cdc2 homologue. DNA sequencing revealed strong amino acid sequence conservation among the cdc2 gene products from pea, yeast and animal cells. Genomic Southern analysis indicated that the cdc2 gene occurs as a single copy in pea. An additional cdc2-like clone was recovered which displays amino acid sequence similarity with that of pea cdc2. The reported cloning and screening strategy, though limited by the availability of appropriate immunological reagents, provides not only an efficient means of screening heterogeneous PCR products generated by degenerate probes and/or low stringency PCR, but also product verification by immunological criteria. PMID- 1883994 TI - Synchronous expression of leghaemoglobin genes in Medicago truncatula during nitrogen-fixing root nodule development and response to exogenously supplied nitrate. AB - Two leghaemoglobin genes from the diploid, autogamous Medicago truncatula (Mtlb1 and Mtlb2) have been cloned and their nucleotide sequences determined. The deduced amino acid sequences encoded by these two genes differ significantly (18%), confirming that they belong to different sub-groups of Medicago leghaemoglobin genes. RNAse protection experiments have been used to show that both genes are transcriptionally active, and are expressed specifically in the nitrogen-fixing root nodule of M. truncatula. Whilst Mtlb1 mRNA is present at approximatively 3-fold higher steady-state levels than Mtlb2 mRNA, the transcription of both genes is triggered concomitantly during nodule development (5 days after inoculation with Rhizobium meliloti), and the ratio of the steady state levels of the two mRNA species remains constant throughout nodule maturation. When the growth medium of nodulated M. truncatula is supplemented with 5 mM KNO3 over a period of 2-3 days there is a progressive drop in specific nitrogen fixation activity to only 20-25% of the original level. This is accompanied with a parallel and synchronous reduction in the quantities of mRNA corresponding to both Mtlb1 and Mtlb2. By contrast, the expression of the nodule parenchyma-specific gene ENOD2 is not significantly modified following nitrate treatment, clearly demonstrating differences in tissue-specific gene regulation in response to combined nitrogen. PMID- 1883995 TI - Isolation and characterization of cDNA clones for NADP-malic enzyme from leaves of Flaveria: transcript abundance distinguishes C3, C3-C4 and C4 photosynthetic types. AB - To study the control of enhanced synthesis of enzymes associated with C4 photosynthesis relative to non-C4 plants, we investigated the expression of NADP malic enzyme (NADP-ME) in different photosynthetic types of Flaveria. Complementary DNA clones encoding NADP-ME were constructed using poly(A)+ RNA from leaves of Flaveria trinervia (C4) and F. linearis (C3-C4) and identified by homology to a cDNA clone (500 bp) encoding NADP-ME from maize (Zea mays L. [39]). The sequence of one clone from each species was determined. The Flaveria clones were 90% homologous over a 564 nucleotide region encoding the carboxy terminal end of the derived polypeptide; sequence similarity to the maize transcript in this region was 71%. Both Flaveria clones detected a 2/3 kb transcript by hybridization to poly(A)+ RNA from expanding leaves of F. trinervia, F. linearis and F. pringlei (C3). The level of transcripts paralleled previously observed NADP-ME activity and abundance differences determined in these species, suggesting that control of the expression of NADP-ME in different photosynthetic types is predominantly at the transcriptional/post-transcriptional level. Southern analysis of genomic DNAs from F. trinervia, F. linearis and F. pringlei indicated a low copy number for this gene in all three species. PMID- 1883996 TI - Expression of the potato leafroll luteovirus coat protein gene in transgenic potato plants inhibits viral infection. AB - Transgenic potato plants, cultivar Desiree, were produced that contained the coat protein gene of potato leafroll luteovirus (PLRV). The transformed potato plants expressed the PLRV coat protein (CP) RNA sequences but accumulation of coat protein in transgenic tissues could not be detected. Upon inoculation with PLRV, the PLRV CP RNA expressing potato plants showed a reduced rate of virus multiplication. PMID- 1883997 TI - Changes in mRNA level rhythmicity in the leaves of Sinapis alba during a lengthening of the photoperiod which induces flowering. AB - A previous study has shown that mRNAs exhibit complex patterns of diurnal rhythms in their quantity in the leaves of Sinapis alba during an 8 h light/16 h dark short day (SD). In order to determine whether this situation is rapidly modified in plants subjected to an extended light treatment, we have used in vitro translation and two-dimensional polyacrylamide gel electrophoresis, together with a strict gel comparison procedure giving a P = 0.03 certitude level, to analyse the mRNA complement at different times during a 22 h light/2 h dark long day (LD). During this LD, complex changes affected about 10% of the mRNAs. Thirty four different patterns were observed. Some diurnal rhythms present in SD are not modified by the lengthening of the light period, but most are affected. Moreover, we have shown that some mRNAs presenting a constant quantity under a SD regime show an increase or a decrease during the first hours of the photoperiod lengthening. In Sinapis, this LD also induces flowering. All the changes in mRNA quantity detected thus parallel the photoperiodic induction of flowering in the leaves and are quantitative; no mRNA was shown to appear or to disappear. PMID- 1883999 TI - Beta-tubulins are encoded by at least four genes in the brown alga Ectocarpus variabilis. AB - Complementary DNA clones of two mRNA species that encode beta-tubulin in the brown alga Ectocarpus variabilis have been isolated. Sequence analysis revealed that the encoded proteins are very similar in primary structure to homologues in other eukaryotes, and differ from each other at six of 447 amino acid residues. The beta 6 message shows a preference for C- or G-terminated codons, using only 49 codons. The beta 5 message has a lesser codon bias, and makes a minor contribution to the beta-tubulin mRNA pool. Southern analysis of E. variabilis DNA demonstrated a beta-tubulin gene family of at least four members. PMID- 1883998 TI - Expression of a bacterial lysine decarboxylase gene and transport of the protein into chloroplasts of transgenic tobacco. AB - A possible approach for altering alkaloid biosynthesis in plants is the expression of genes encoding key enzymes of a pathway such as lysine decarboxylase (ldc) in transgenic plants. Two strategies were followed here: one focused on expression of the gene in the cytoplasm, the other on subsequent targeting of the protein to the chloroplasts. The ldcgene from Hafnia alvei was therefore (a) placed under the control of the 1' promoter of the bidirectional Tr promoter from Agrobacterium tumefaciens Ti-plasmid, and (b) cloned behind the rbcS promoter from potato fused to the coding region of the rbcS transit peptide. Both ldc constructs, introduced into Nicotiana tabacum with the aid of A. tumefaciens, were integrated into the plant genome and transcribed as shown by Southern and northern hybridization. However, LDC activity was only detectable in plants expressing mRNA under the control of the rbcS promoter directing the LDC fusion protein into chloroplasts with the aid of the transit peptide domain. In plants expressing the processed bacterial enzyme cadaverine levels increased from nearly zero to 0.3-1% of dry mass. PMID- 1884000 TI - The structure of a Phaseolus vulgaris cDNA encoding the iron storage protein ferritin. AB - A cDNA containing the entire coding region for the iron storage protein ferritin has been isolated from the French bean plant, Phaseolus vulgaris L. cv. Tendergreen. Ferritin protein was purified from young leaves and shoot meristem tissue and used to raise antisera in mice. A lambda gt11 cDNA library was constructed from seed-derived poly(A)+ RNA, and screened with the mouse anti ferritin serum. A 1.2 kb immunopositive phage DNA insert was isolated and sequenced. The derived amino acid sequence shows substantial similarity with other ferritin sequences. The 5' untranslated region contains two out-of-frame AUG codons, a region of extreme pyrimidine composition bias and potentially stable secondary structure. PMID- 1884001 TI - Nucleotide sequence of the large subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase from the green alga Bryopsis maxima. PMID- 1884002 TI - A copy of exon 3-intron 3 from the barley aleurain gene is present on chromosome 2. AB - A genomic clone from Hordeum vulgare L. cv. Himalaya contains 700 bp of DNA that is homologous with a high degree of nucleotide sequence similarity to exon 3 intron 3 from the gene for the thiol protease, aleurain. Genomic Southern blot mapping data indicate that this clone in phage lambda had not undergone rearrangement, and no other sequences homologous to aleurain are present on it. Although exon 3 in aleurain encodes the polypeptide region cleaved during proteolytic processing of the proenzyme to its mature form, we do not know if the copy is expressed in some other protein. We have mapped the aleurain gene to chromosome 1, and this copy of exon 3-intron 3 to chromosome 2. PMID- 1884003 TI - Nucleotide sequence and transcription of maize plastid genome Bam HI fragment 14 containing ORF170. PMID- 1884004 TI - Characterization of the gene encoding the 10 kDa polypeptide of photosystem II from Arabidopsis thaliana. AB - We report the characterization of a 1388 bp genomic fragment from Arabidopsis thaliana that encompasses the entire transcription unit of the gene encoding the precursor of 10 kDa polypeptide of photosystem II, 495 bp of the 5' flanking region and 73 bp of the 3' boundary of the gene. The deduced protein shows 78% and 73% homology, respectively, with its homologues from potato and spinach. The transcription of the gene seems to be greatly enhanced by light and only transcribed in substantial amounts in leaves and stems. Analysis of the putative 5' regulatory region of the gene shows homology with several cis-elements involved in light regulation of the transcription. PMID- 1884005 TI - Nucleotide sequence of Cab-8, a new type I gene encoding a chlorophyll a/b binding protein of LHC II in Pisum. PMID- 1884006 TI - Sequence analysis of cDNA encoding phosphoenolpyruvate carboxylase from cultured tobacco cells. PMID- 1884007 TI - Nucleotide sequence and expression of the ribosomal protein L2 gene in pea chloroplasts. AB - We sequenced the nucleotides around the rpl2 gene, encoding the ribosomal protein L2, in pea (Pisum sativum cv. Alaska) chloroplasts and analyzed the expression of the rpl2 gene. During deetiolation, accumulation of the rpl2 transcript did not require de novo protein synthesis on chloroplastic ribosomes, in contrast to that of most chloroplast-encoded genes. This suggested that the mechanism involved in the expression of rpl2 differed from that of most chloroplast-encoded genes. PMID- 1884008 TI - Cytosolic localization in transgenic plants of the rolC peptide from Agrobacterium rhizogenes. AB - The rolC gene of Agrobacterium rhizogenes codes for a peptide with an apparent molecular weight of approximately 20 kDa. Immunolocalization of the rolC peptide, in leaves of transgenic plants which are genetic mosaics for the expression of the rolC gene, is restricted to the phenotypically altered sectors. Subcellular fractionation of homogenates from 35S-rolC transgenic leaves shows the cytosolic localization of the rolC peptide. PMID- 1884009 TI - Nucleotide sequence of gene oee2-A and its cDNA encoding 23 kDa polypeptide of the oxygen-evolving complex of photosystem II in tobacco. PMID- 1884010 TI - Direct amplification of plant genomic DNA from leaf and root pieces using PCR. PMID- 1884011 TI - Auxin-induced expression of the soybean GH3 promoter in transgenic tobacco plants. AB - The gene encoding the auxin-responsive GH3 mRNA (G. Hagen, A. Kleinschmidt, TJ. Guilfoyle, Planta 162: 147-153 (1984] from soybean was cloned, and its sequence and transcription initiation site were determined. The promoter of the GH3 gene has been fused to the open reading frame of the Escherichia coli uidA gene which encodes beta-glucuronidase (GUS). This fusion gene was introduced into tobacco via Agrobacterium tumefaciens-mediated transformation, and the expression of the gene was examined by fluorometric assay and histochemical staining of young R1 tobacco seedlings and mature plants. In transgenic tobacco plants that have not been exposed to exogenous auxin, expression of the fusion gene is largely restricted to roots of young green plants and developing floral organs, including ovules, developing seeds, and pollen, of mature plants. Application of exogenous auxin to tobacco seedlings or plant organs results in a greater than 50-fold increase in expression of GUS. Auxin-induced GUS expression is greatest in vascular tissue, but not restricted to this tissue. The auxin-deduced GUS expression was characterized for kinetics, auxin specificity and dose response. PMID- 1884012 TI - Mouse hematopoietic stem cells. PMID- 1884013 TI - A clinical and experimental study on all-trans retinoic acid-treated acute promyelocytic leukemia patients. AB - Fifty patients with acute promyelocytic leukemia (APL) have been treated with all trans retinoic acid (RA). In vitro induced differentiation of primarily cultured bone marrow cells from the patients, colony-forming unit granulocyte-macrophage (CFU-GM) and L-CFU colony-forming assays, and karyotype analysis were performed over the treatment course. The very high bone marrow complete remission (CR) rate (94%) suggested that all-trans RA was superior to conventional chemotherapeutic regimens for the treatment of APL. The leukemic clone was reduced by RA-induced terminal differentiation and loss of proliferation capacity of leukemic cells. Relapse after CR in about 40% of patients was the major reason for the failure of the RA treatment. Patients who relapsed after a chemotherapy-maintained CR could be effectively reinduced to second CR by RA. However, if relapse occurred after a CR maintained by both RA and chemotherapy, the sensitivity of newly emerged leukemic clones to RA was greatly reduced. Therefore, it is suggested that RA should be replaced by conventional chemotherapy as soon as CR is achieved. Laboratory studies proved valuable in selecting cases for RA therapy and in predicting therapeutic effects and prognosis. PMID- 1884015 TI - Temporal replacement of donor erythrocytes and leukocytes in nonanemic W44J/W44J and severely anemic W/Wv mice. AB - The dominant white spotting, W, locus in the mouse encodes Kit, a receptor molecule with cytosolic tyrosine kinase activity. Mutations in Kit deplete hematopoietic cells by an as yet unknown mechanism, but one that presumably affects the early progenitors of all cell lineages. To examine cell lineage specific changes caused by different W mutations, we injected genetically marked normal marrow cells into mutant mice and monitored repopulation kinetics. In the present report, we compare repopulation of the various peripheral blood cells in nonanemic W44J/W44J and severely anemic W/Wv mice administered increasing increments of donor cells. At all doses of cells tested, donor erythrocyte repopulation precedes leukocyte repopulation regardless of the recipient phenotype. There is, in fact, little difference in the rate or extent of nonerythroid repopulation in W44J/W44J mice injected with between 6 x 10(6) and 2 x 10(7) donor cells. The fact that donor cells rapidly replace erythrocytes, even in the nonanemic W44J/W44J host, while other cell lineages become donor type more slowly provides further evidence that mutations at the W locus are especially damaging to erythrocyte progenitors. We suggest that host nonerythroid hematopoietic cells compete with normal cells, probably at the level of early progenitors rather than at the level of the totipotent hematopoietic stem cell. The fact that successively higher doses of donor cells do not markedly alter nonerythroid repopulation kinetics implies that it may be possible to maximize autologous therapeutic marrow transplantation. PMID- 1884014 TI - A phase I trial of recombinant human interleukin-1 beta alone and in combination with myelosuppressive doses of 5-fluorouracil in patients with gastrointestinal cancer. AB - We studied escalating doses of recombinant human interleukin-1 beta (IL-1 beta) alone and after a myelosuppressive dose of 5-fluorouracil (5-FU) in patients with gastrointestinal cancer. Transient neutropenia, monocytopenia, and lymphocytopenia were observed followed by a 1.3- to 6.0-fold (mean, 3.46-fold) dose-dependent neutrophil leukocytosis (P less than .00001) on the days of IL-1 beta administration. Increases in platelet counts were observed at a median of 14 days (range, 6 to 23) after IL-1 beta administration. Transient hypoglycemia, rebound hyperglycemia, elevations in serum cortisol, and C-reactive protein were observed. Side effects included fever, rigors, and headache in the majority of patients. Hypotension was observed in three of five patients at the highest dose level (0.1 micrograms/kg) and was dose-limiting. Fewer days of neutropenia were noted after 5-FU plus IL-1 beta than after 5-FU alone; however, this difference did not reach statistical significance. These data show that IL-1 beta has stimulatory effects in human hematopoiesis. PMID- 1884016 TI - Effects of human interleukin-6 on megakaryocyte development and thrombocytopoiesis in primates. AB - Recombinant human interleukin-6 (IL-6) has previously been shown to increase platelet counts in mice and primates. To elucidate the mechanisms underlying this phenomenon, serial analyses were performed on megakaryocytes obtained from rhesus monkeys treated for 8 days with 30 micrograms/kg/d of recombinant human IL-6. Platelet counts increased to a maximum of 7.8 x 10(5)/microL with biphasic peaks on days 7 and 12 without significant changes in platelet volumes. Large increases in DNA content were seen by two-color flow cytometry and digital image analysis. Ploidy distribution underwent a significant shift between study days 3 and 11 (P less than .0001) with large increases in the frequency of 64N and 128N megakaryocytes. The modal ploidy increased from the normal 16N to 64N. Megakaryocyte size, as measured by area, was increased 2- to 2.7-fold. On day 3, multiple megakaryocytes were seen in endomitosis, along with an abundance of young cells with wide, organelle-free peripheral zones. The giant megakaryocytes seen on days 5 to 7 exhibited marked membrane hyperplasia that occupied much of the cell. Emperipolesis occurred frequently, as did megakaryocyte cell death. No giant platelets were seen. We conclude that IL-6 significantly alters the process of megakaryocyte maturation and thrombocytopoiesis, and that these effects, at least in the doses of IL-6 administered, should not be equated with the physiologic mechanisms operative during accelerated platelet production. PMID- 1884017 TI - Changes in splenic microcirculatory pathways in chronic idiopathic thrombocytopenic purpura. AB - The spleen plays a central role in the pathogenesis of chronic idiopathic thrombocytopenic purpura (ITP); it produces massive quantities of antiplatelet antibodies, leading to accelerated phagocytosis of platelets. Lymphoid hyperplasia typically occurs in the spleen, characterized by large numbers of lymphatic nodules with active germinal centers. Whether changes in splenic microcirculatory pathways also occur is not known. We have studied this question by scanning electron microscopy of corrosion casts, comparing spleens removed from patients with ITP with normal spleens obtained from organ transplant donors. The casts demonstrate two major changes in microcirculatory pathways in ITP. Firstly, a striking proliferation of arterioles and capillaries is found in the white pulp and marginal zone (MZ), seen as extensive vascularization in 92.3% of lymphatic nodules (n = 191) versus 0.6% (n = 224) in normal spleens. Secondly, the marginal sinus, a series of flattened, anastomosing vascular spaces between the white pulp and MZ, is absent in 89.4% of lymphatic nodules versus 4.9% in normal spleens. The cause of these microcirculatory changes, which may not be exclusive to ITP, is presently unknown. Absence of the marginal sinus may affect distribution of blood flow through the MZ such that platelets spend increased amounts of time in the proximity of macrophages. In the presence of antiplatelet antibodies found in ITP spleens, this delayed transit would lead to greatly increased platelet destruction. PMID- 1884018 TI - Lambda-like and V pre-B genes expression: an early B-lineage marker of human leukemias. AB - V pre-B and lambda-like genes are selectively expressed in human pre-B cells and encode polypeptide chains that associate in a mu-pseudolight chain complex that may regulate some crucial steps of early B-cell differentiation. We have followed by polymerase chain reaction and Northern blot analysis the expression of these "pre-B-specific" genes in correlation with the status (rearranged v germline) of Ig gene loci (H, kappa, lambda) in a panel of 32 leukemias pertaining mostly to the B lineage and including a number of ambiguously characterized samples. All cells that had rearranged the H locus only expressed V pre-B and lambda-like transcripts, in agreement with a pre-B status. In this group, some biphenotypic leukemias (mostly My/B) might, in fact, be already engaged in the B lineage. Rearrangement of V kappa or V lambda loci correlated with the disappearance of the pre-B gene products. In a pre-B acute lymphoblastic leukemia cell line that was induced to mature to the B-cell stage in culture upon kappa gene rearrangement, the mu-pseudolight chain complex was actually replaced by the classical mu-kappa molecule. Finally, V pre-B and lambda-like genes were found expressed in two leukemic cells that had retained all Ig loci in germline configuration. This finding raises the possibility of having an early pro-B progenitor in which V pre-B and lambda-like products associate with a H chain surrogate in a complex that would trigger an early event of B-cell differentiation such as the H locus rearrangements. PMID- 1884019 TI - Transferrin-independent iron uptake supports B lymphocyte growth. AB - Raji, a malignant B-lymphocyte cell line containing Epstein-Barr virus genomic elements, has been conditioned to proliferate optimally in transferrin (Tf)-free medium containing a very low concentration of an iron salt. We provide evidence that an Tf-independent iron uptake system is physiologically important for maintaining the growth of these cells. The data show that Raji cells take up iron from iron salts using a relatively high-capacity, low-affinity, temperature- and calcium-dependent uptake system. The apparent capacity of this system increases when: (1) cells are cultured in Tf-free medium containing high concentrations of iron salt as opposed to medium containing Tf; and (2) when the iron salt concentration of Tf-free medium is lowered to about 1.6 mumol/L. Cellular iron uptake also increases when a maximum number of cells are in S and G2 and M cell phases of the cell cycle. The cells are sensitive to growth inhibition by the addition of deferoxamine. This evidence supports the hypothesis that certain malignant lymphocytes, under iron deplete conditions, fulfill an iron requirement for proliferation by an adaptation such as Tf-independent iron uptake. PMID- 1884020 TI - Administration of interleukin-2 (IL-2) results in increased plasma concentrations of IL-5 and eosinophilia in patients with cancer. AB - Peripheral eosinophilia is almost invariably observed during the course of interleukin-2 (IL-2) therapy and is frequently accompanied by the development of a capillary leak syndrome characterized by edema, weight gain, and oliguria. We studied five patients with advanced malignancy treated with IL-2. Eosinophilia was not present initially but developed in all patients late in the course of therapy, with counts ranging from 2,328/mm3 to 15,958/mm3. In all patients, there was a temporal relationship between the infusion of IL-2 and the appearance of elevated plasma concentrations of IL-5, a growth factor for eosinophils. Granulocyte-macrophage colony-stimulating factor was not detectable in plasma. IL 4 and gamma-interferon plasma levels were variably elevated. Plasma concentrations of major basic protein, a toxic eosinophil granule protein, began increasing before eosinophil counts increased. By the time of the third IL-2 infusion, high concentrations of major basic protein were present in all five patients (up to 5,600 ng/mL) and skin biopsies showed major basic protein deposition in the dermis. Four patients developed significant capillary leak syndrome and all of these patients showed markedly elevated major basic protein levels. The lowest peak plasma concentration of major basic protein (1,751 ng/mL) was observed in the one patient who did not develop edema and weight gain. These results suggest that IL-2 induces IL-5 leading to marked peripheral eosinophilia and extravascular eosinophil degranulation. The release of toxic eosinophil products at extravascular sites and in the circulation may contribute to the pathogenesis of the capillary leak syndrome complicating IL-2 therapy. PMID- 1884021 TI - Presenting features and prognosis of chronic lymphocytic leukemia in younger adults. AB - We have analyzed 117 younger patients with chronic lymphocytic leukemia (CLL) (mean age, 44.5 years; SD, 4.8; range, 19 to 49; male/female ratio, 2.08) with three main objectives: (1) to see whether these patients have distinctive presenting clinical features; (2) to investigate the impact of the disease on survival; and (3) to analyze whether already well-known prognostic factors are also useful when applied to these patients. As compared with an older age population (greater than or equal to 50 years), there were no major differences in presenting features except for an increased proportion of males (2.08 v 1.21; P less than .025) and a higher hemoglobin level (13.47 +/- 2.70 g/dL v 12.84 +/- 2.77 g/dL; P less than .05) in the younger group. Median survival is 12.3 years (expected median from a control group, 31.2 years). Clinical stages, bone marrow patterns, blood lymphocyte counts, and its doubling time are all useful to separate different risk groups of patients. Whereas patients with favorable prognostic factors have a survival probability of about 80% 14 years after diagnosis, those with poor prognostic features have a median survival of less than 3 years. It is concluded that CLL in younger adults has no major distinctive presenting features and that known prognostic factors are useful to separate different risk groups of patients. These results should be of help in planning therapy for younger persons with CLL. PMID- 1884022 TI - Enhanced detection of the t(14;18) translocation in malignant lymphoma using pulsed-field gel electrophoresis. AB - The t(14;18) chromosomal translocation that results in the juxtaposition of the bcl-2 proto-oncogene with the heavy chain JH locus is a common cytogenetic abnormality in human lymphoma. In particular, it is seen in about 85% of follicular lymphoma (FL) and up to one-third of diffuse lymphomas (DL). The chromosome 18 breakpoints have been shown to cluster into two regions. The major breakpoint region (mbr) within the 3' untranslated region of the bcl-2 proto oncogene accounts for approximately 60% of the cases and the minor cluster region (mcr) 30 kb 3' of bcl-2 accounts for approximately 25% of the breakpoints. Because of variability in the position of the breakpoint, detection of the t(14;18) by Southern blot analysis provides an important clonal marker for the tumor. However, conventional electrophoresis (CE) fails to detect the translocation in 15% to 25% of cases. We have applied pulsed-field gel electrophoresis (PFGE) to the detection of the t(14;18) in a series of lymphoma prospectively analyzed by CE, polymerase chain reaction (PCR), and cytogenetic analysis. PFGE readily detected t(14;18) rearrangements as indicated by comigration of bands detected with probes for the mbr region (chromosome 18) and the JH locus (chromosome 14). In a series of 40 patients with FL, this method proved to be the most comprehensive for detection of the translocation compared with standard methods; in fact, in one case only PFGE was able to detect the chromosomal rearrangement. Ten percent of the FL cases were negative by all methods tested. In a separate analysis of matched tissue specimens from cases of tumor progression of FL to diffuse lymphoma, PFGE detected a common t(14;18) rearrangement confirming a clonal origin in seven of seven cases, whereas CE detected a rearrangement in only three of seven cases. Overall, PFGE was able to detect a translocation in 8 of 12 cases that were negative by CE and four of eight negative by cytogenetic analysis. In conclusion, PFGE analysis is more comprehensive than CE, PCR, and cytogenetic analysis for the detection of the t(14;18) breakpoint in tissue biopsies of malignant lymphoma. PMID- 1884023 TI - Inhibitory effect of interleukin-4 on the in vitro growth of Ph1-positive acute lymphoblastic leukemia cells. AB - We investigated the effect of recombinant human interleukin-4 (rhIL-4) on the in vitro growth of human leukemia cells in liquid culture and 3H-thymidine incorporation and found inhibitory effects on the growth of leukemic cells from patients with Ph1-positive acute lymphoblastic leukemia (Ph1 ALL) and three Ph1 ALL cell lines. However, no inhibitory effects were seen in Ph1-positive leukemic cell lines derived from patients with chronic myelogenous leukemia in blast crisis and various types of Ph1-negative leukemia cells, including B-lineage leukemia cells. In a flow cytometry assay of IL-4 receptor (IL-4R), all three Ph1 positive ALL cell lines showed the presence of IL-4R on their cell surfaces, and the IL-4-dependent inhibition on the growth of Ph1-positive ALL cells was abrogated by the addition of either monoclonal or polyclonal antibodies against rhIL-4. Other cytokines, including IL-2, IL-3, granulocyte-macrophage colony stimulating factor (CSF), granulocyte-CSF, and IL-6, showed no inhibitory effects on the growth of Ph1-ALL cells, but tumor necrosis factor-alpha (TNF-alpha) and interferon (IFN)-alpha, -beta, and -gamma displayed slight inhibitory effects in a high concentration. The growth inhibition induced by rhIL-4 in the Ph1-positive ALL cells was not abrogated by the addition of antibodies against either IFN gamma or TNF-alpha. Furthermore, these cells showed no significant production of IFN-alpha, -beta, or -gamma or TNF-alpha after exposure to rhIL-4, thus indicating that the growth inhibition of Ph1-positive ALL cells by rhIL-4 is not associated with IL-4-stimulating production of these factors. rhIL-4 caused significant inhibition of the tyrosine kinase activity in these Ph1-positive ALL cells, similar to Herbimycin A, an inhibitor of tyrosine kinase that inhibited the tyrosine kinase activity in these cells. Our finding suggests that the clinical evaluation of rhIL-4 may offer promising therapeutic possibilities for patients with Ph1-positive ALL. PMID- 1884024 TI - VpreB gene expression in hematopoietic malignancies: a lineage- and stage restricted marker for B-cell precursor leukemias. AB - We show here that analysis of VpreB gene transcription can be a specific way to identify acute leukemias of cells at very early stages of B-cell development. Northern blot analysis of RNAs from 63 leukemia samples showed that VpreB RNA was present in malignancies of precursor B cells, the expression being a feature of both common acute lymphoblastic leukemia (ALL) (CD10+) and null ALL (CD10-). It was absent from malignancies of mature B cells (surface Ig positive), from acute leukemias of the T-cell lineage and granulocyte-macrophage lineages, and from normal tonsil B and T lymphocytes. Chronic myeloid leukemia blast crises of the B precursor-cell type expressed the VpreB gene while myeloid blast crises did not. VpreB RNA was also expressed in the neoplastic cells of one of three patients with acute undifferentiated leukemias. These data show that VpreB RNA expression is a marker of the malignant forms of precursor B cells, and that it appears at least as early as cytoplasmic CD22 and CD19 in tumors of the B-cell lineage. PMID- 1884025 TI - Improvement of mouse beta-thalassemia by recombinant human erythropoietin. AB - Homozygous beta thalassemic mice received 50 U (1,660 U/kg) of recombinant human erythropoietin (rhEpo) 5 days a week for 2 weeks. Hemoglobin increased from 9.2 +/- 0.6 g/dL to 10.5 +/- 0.4 g/dL (P = .002) and hematocrit increased from 29.2% +/- 0.9% to 34.1% +/- 1.9% (P = .0014). The beta minor/alpha globin chain synthesis ratio increased slightly but significantly between day -4 (0.75 +/- 0.07) and day 4 (0.81 +/- 0.04) (P = .01) and reached a minimum ratio (0.67 +/- 0.03) on day 15 (P = .001), being parallel to reticulocyte counts and to the incorporated trichloracetic acid (TCA)-insoluble radioactivity, therefore parallel to the erythropoietic output in thalassemic mice, as in normal mice. Erythrocyte defects were improved in beta thalassemic mice treated by rhEpo: membrane-associated alpha globin was significantly decreased (P less than .01), thiol group reactivity of ankyrin was significantly improved (P less than .05), spectrin alterations were reduced, and deformability of mouse thalassemic red blood cells was normalized. These results provide experimental criteria for modulating globin chain imbalance necessary for the therapy of human beta thalassemia intermedia, and suggest that rhEpo might be of interest to improve the red blood cell mass and reduce erythrocyte alterations in this disease. PMID- 1884026 TI - Molecular basis for elliptocytosis associated with glycophorin C and D deficiency in the Leach phenotype. AB - Glycophorin C (GPC) and glycophorin D (GPD) are highly glycosylated integral membrane proteins of human erythrocytes encoded by the same gene and associated with expression of Gerbich blood group system antigens. GPC/D deficiency (the Leach phenotype) is a rare condition usually found after identification of Gerbich blood group system antibodies in persons undergoing prenatal or pretransfusion evaluation. In all cases, the Leach phenotype has been associated with elliptocytosis. Characterization of the molecular basis of this phenotype in three previously uninvestigated families has shown that the most common genetic basis of GPC/D deficiency is deletion of exons 3 and 4 of the GPC gene. However, in one family, the Leach phenotype appeared due to a deletion of one nucleotide in exon 3, causing a frameshift mutation in the messenger RNA and premature generation of a stop codon. The GPC and GPD protein sequences are therefore interrupted in the extracellular domain and probably intracellularly degraded. PMID- 1884027 TI - Myeloablative chemoradiotherapy and autologous bone marrow infusions for treatment of neuroblastoma: factors influencing engraftment. AB - Bone marrow harvested from cancer patients for autologous bone marrow reinfusion (ABMR) after myeloablative treatment may be injured, in both its proliferating and stromal cell pools, by either previous treatment or manipulation at the time of harvest. We have examined the relative effects of seven covariates on hematologic recovery after ABMR in children with neuroblastoma (NBL) using univariate and step-up analysis. We measured recovery by times to achieve (1) white blood cell counts greater than 1,000/microL; (2) absolute neutrophil counts greater than 500/microL; and (3) platelet counts greater than 20,000/microL without transfusion. In univariate analysis, recovery was significantly associated with the amount of prior chemotherapy and the interval between last chemotherapy and marrow harvest. Patient sex, the number of granulocyte macrophage colonies infused, harvest-to-freeze interval, and use of purging were marginally associated. After adjusting for potential confounders in a multivariate model, the amounts of chemotherapy and granulocyte-macrophage colonies infused were independently significant predictors of time to total white blood cell count recovery; chemotherapy courses and chemo-to-harvest interval were predictors of neutrophil count recovery; and sex, use of purging, and harvest-to-freeze interval were marginal predictors of platelet recovery. The speed of hematologic recovery after ABMR seems to depend mainly on pre-existing factors and marginally on manipulation of the marrow after harvest. These factors may affect both proliferating and stromal cell pools. PMID- 1884028 TI - Impaired erythropoietin production in mice treated with cyclosporin A. AB - Because recent data indicate that erythropoietin (Epo) production is defective in allogeneic bone marrow transplant (BMT) patients, we investigated the role of the immunosuppressant, nephrotoxic, agent cyclosporin A (CsA) on renal Epo production using an animal model. Mice were injected with 1.0 to 40.0 mg/kg/d CsA for 15 days. Thereafter, circulating Epo levels were evaluated in both intact animals and in mice made anemic with phenylhydrazine (PHZ). Serum Epo levels measured in CsA-treated animals were then compared with the predicted levels, which had been calculated in a reference population of normal, either intact or anemic, mice. In CsA-treated, intact animals both hematocrit and serum Epo levels were not significantly different from controls. However, serum Epo levels in CsA-treated, anemic mice were significantly lower than those expected in a control population of untreated, anemic mice with similar degrees of anemia. No significant increase in serum creatinine was recorded even at the highest doses of CsA used, nor were we able to document signs of renal toxicity by histologic examination of the kidneys. Therefore, therapeutical doses of CsA appear to affect the production of Epo under conditions in which the demand of the hormone is increased, as in response to anemia. We suggest that a subclinical kidney toxicity produced by CsA might have a role in the pathogenesis of the impaired Epo production observed in BMT patients, and may contribute to a delayed erythroid engraftment in at least some BMT patients. PMID- 1884029 TI - Treatment type and amount influenced human immunodeficiency virus seroprevalence of patients with congenital bleeding disorders. AB - Two hundred and eighty-two patients with congenital bleeding disorders received blood component replacement therapy between January 1979 and April 1985, were followed-up by the Puget Sound Blood Center's Hemophilia Care Program, and were tested for antibody to human immunodeficiency virus (HIV). Serologic results were obtained at least 1 year after the last exposure to volunteer donor products that were prepared before donor HIV screening or after the last exposure to concentrates produced before the manufacturer's use of treatment methods for inactivation of HIV. In all, 106 patients were anti-HIV positive. The risk of HIV infection was greater in patients with more severe bleeding tendencies, greater exposure to components, and exposure to lyophilized concentrates from large pools of donors. Of 100 patients with hemophilia A who only received cryoprecipitate from volunteer donors from Washington State (during the 6.3-year period), 14% had become anti-HIV positive. Of 27 patients receiving mostly cryoprecipitate but also being exposed to a single lot of concentrate during the same period, 13 (48%) were positive. Of 49 patients treated predominantly or solely with factor VIII concentrates during this period, 43 (88%) were anti-HIV positive. Of 29 patients with von Willebrand disease, four were anti-HIV positive, including 2 of 26 receiving only cryoprecipitate and two of three who had received a single dose of factor VIII concentrate. Of 19 patients who were treated solely with volunteer donor plasma, all remained anti-HIV negative. Of 47 patients exposed to factor IX concentrate, 28 (60%) were positive. Data relevant to the risk of HIV transmission subsequent to screening of the volunteer donor population were also obtained. Treatment records of 55 hemophilia A patients who have remained anti HIV negative through at least June 1990 showed exposure to 71,173 screened donors from May 1985 through December 1989, and all 55 patients have remained anti-HIV negative. PMID- 1884030 TI - [Occlusal symptomatology]. PMID- 1884031 TI - [Radiographic evaluation of the temporomandibular joint]. PMID- 1884032 TI - [Chromatic effect test in reconstruction of anterior teeth]. PMID- 1884033 TI - [Oral pathology of pharmacological origin]. PMID- 1884034 TI - [Photopolymerization of composite: S.E.M. observations]. PMID- 1884035 TI - [Peri-implant osseous regeneration]. PMID- 1884036 TI - [SEM and TEM on odontoblast extension in the enamel free area (EFA) of rat and mouse molars]. PMID- 1884037 TI - [The effect of fluoride on teeth]. PMID- 1884038 TI - [Porcelain veneers: construction technique]. PMID- 1884039 TI - [Stress and the problem of pain in pain-dysfunction syndrome of the masticatory system. (P.D.S.M.S.)]. PMID- 1884040 TI - [The Delaire mask]. PMID- 1884041 TI - [Operative sequence in the execution of pedodontic crowns]. PMID- 1884042 TI - [Relations between posture, locomotion, dentition, hand and TMJ, from origins to man]. PMID- 1884044 TI - [Radio-video-graphy: the future of dental radiology with real time imaging]. PMID- 1884043 TI - [Antimicrobial drugs in root canals]. PMID- 1884045 TI - [Osseointegrated implants. An elegant and functional approach in daily practice]. PMID- 1884046 TI - [Cranial dynamics]. PMID- 1884047 TI - [Malocclusion and scleroderma]. PMID- 1884048 TI - [The lips in myofunctional therapy]. PMID- 1884049 TI - [Optic microscope study of degree of adaptability of glass-ionomer cement]. PMID- 1884050 TI - From audit to quality and beyond. PMID- 1884051 TI - "Second line" drugs for rheumatoid arthritis. PMID- 1884052 TI - Child health surveillance lists. PMID- 1884053 TI - When sex is a headache. PMID- 1884054 TI - The citizen's charter and the NHS. PMID- 1884055 TI - Testing US doctors for HIV. PMID- 1884056 TI - Alcohol consumption and risk of coronary heart disease. AB - OBJECTIVE: To investigate the hypothesis that the apparent protective effect of habitual alcohol consumption on coronary heart disease is due to drinkers at high risk of coronary heart disease becoming non-drinkers. DESIGN: Case-control population based study. Data were obtained from interviews with patients with non fatal myocardial infarction and their controls and with the next of kin of those who had died of coronary heart disease and their controls. SETTING: Auckland, New Zealand. SUBJECTS: Two groups of cases were studied. The first comprised 227 men and 72 women with non-fatal myocardial infarction identified from a population based surveillance programme for coronary heart disease; controls were 525 men and 341 women randomly selected from the same population group and matched for age and sex. The second group comprised 128 men and 30 women who had died of coronary heart disease and had been identified from the surveillance programme; controls were a sample of the previous control group and comprised 330 men and 214 women matched for age and sex. All participants were aged 25-64 years and without diagnosed coronary heart disease. MAIN OUTCOME MEASURES: Regular alcohol consumption; high density lipoprotein cholesterol and low density lipoprotein concentrations. RESULTS: Men with myocardial infarction and men who had died of coronary heart disease were more likely to have been never drinkers (had never drunk more than once a month) than controls (18% v 12% and 23% v 13% respectively). After possible confounding factors had been controlled for, people in all categories of drinking (up to more than 56 drinks per week) had at least a 40% reduction in risk of fatal and non-fatal coronary heart disease compared with never drinkers. Former drinkers also had a lower risk of non-fatal myocardial infarction than never drinkers (relative risks 0.41 and 0.10 in men and women respectively) but a similar risk of death from coronary heart disease. The reduction in risk was consistently greater in women than in men in all drinking categories but there was no clear dose-response effect in either sex. CONCLUSIONS: The results support the hypothesis that light and moderate alcohol consumption reduces the risk of coronary heart disease. This protective effect in this population was not due to the misclassification of former drinkers with a high risk of coronary heart disease as non-drinkers. PMID- 1884057 TI - Prevalence of primary fibromyalgia in the Finnish population. AB - OBJECTIVE: To obtain descriptive epidemiological data on fibromyalgia and its components in a representative sample of the Finnish population. DESIGN: Cross sectional study of 8000 Finns aged 30 or more invited for screening and a main examination for musculoskeletal disorders and other major disorders. SETTING: A mobile clinic. POPULATION: 7217 subjects who attended the screening phase; 3434 subjects positive on screening who attended the main examination for musculoskeletal disorders. MAIN OUTCOME MEASURES: Musculoskeletal, mental, and other symptoms detected by interview and questionnaire; results of standardised clinical examination of the musculoskeletal system; operational definition of fibromyalgia; mortality at 10 years. RESULTS: The prevalence of fibromyalgia was low (54 cases; 0.75%) and related to age (peak prevalence at 55-64 years), female sex (twice as prevalent in women), occupation (no cases among 1596 white collar professionals), level of education (strong inverse gradient), and high levels of physical stress at work. No significant associations were found with body mass index, smoking, or mental stress at work. The prevalence of fibromyalgia was sensitive to even minor modifications of the definition. Fibromyalgia was strongly coincident with many other disorders, especially musculoskeletal conditions. Fibromyalgia did not predict mortality. CONCLUSION: Descriptive epidemiological data offer little support for the concept of fibromyalgia. PMID- 1884058 TI - Efficacy of fixed minidose warfarin prophylaxis in total hip replacement. AB - OBJECTIVE: To determine whether a small fixed perioperative dose of warfarin would prevent deep vein thrombosis after total hip replacement. DESIGN: Prospective, randomised, double blind placebo controlled trial. SETTING: Winford Orthopaedic Hospital, Bristol. SUBJECTS: 148 patients having primary total hip replacement. INTERVENTION: Warfarin 1 mg given daily for one week before and three weeks after surgery. MAIN OUTCOME MEASURE: Deep vein thrombosis diagnosed by the iodine-125 labelled fibrinogen uptake method. RESULTS: Deep vein thrombosis occurred in 25 (34%) of the patients given warfarin and 19 (26%) of the controls (difference 8%; 95% confidence interval -6.8% to 22.8%). CONCLUSION: Fixed minidose warfarin does not prevent deep vein thrombosis after total hip replacement. PMID- 1884060 TI - Prevention of venous thrombosis with minidose warfarin after joint replacement. PMID- 1884059 TI - Liver transplantation after paracetamol overdose. AB - OBJECTIVE: To evaluate the role of liver transplantation after paracetamol overdose. DESIGN: Prospective study of consecutive candidates for transplantation and performance of transplantation over 18 months. SETTING: Liver unit, King's College Hospital, London. MAIN OUTCOME MEASURES: Fulfilment of indicators of poor prognosis, selection for transplantation, transplantation, survival. RESULTS: 30 of 37 patients considered to have a reasonable prognosis with intensive medical care survived. Of 14 of 29 patients considered to have a very poor prognosis and registered for urgent liver transplantation, six received liver transplants, four of whom survived, while seven died and one survived without a transplant. Three of 15 patients with poor prognostic indicators but not selected for transplantation survived. CONCLUSION: Liver transplantation will have a definite but limited role in the management of fulminant hepatic failure induced by paracetamol. PMID- 1884061 TI - Admission to child health surveillance lists: the views of FHSA general managers and general practitioners. AB - OBJECTIVES: To find out the sources of advice that were helpful to managers of family health services authorities in drawing up the criteria for admission of general practitioners to the child health surveillance lists; to determine the criteria used for admission of general practitioners to the family health services authorities' child health surveillance lists; to find out the changes general practitioners have made in child health surveillance in their practices; to determine the experiences of general practitioners relating to admission to the child health surveillance lists and to training in child health surveillance. DESIGN: Survey by postal questionnaire. SUBJECTS: General managers of all family health services authorities in England and Wales; all general practitioners in Yorkshire and Humberside. RESULTS: Managers of 80 of 93 family health services authorities replied (86%). A total of 62 (78%) found local community paediatricians helpful in compiling criteria for admission to child health surveillance lists, and 46 (57%) found national guidelines helpful. Fifty seven (71%) accepted general practitioners who had completed an approved course, and 45 (56%) accepted those with three or more years' experience of child health surveillance. Of the 1966 questionnaires sent to general practitioners, 1233 were satisfactorily completed (63%). Of the 919 respondents who had applied to be put on child health surveillance lists, 673 (73%) had been permanently accepted; of these, 441 (65%) had done an approved course and 375 (56%) had had three or more years' experience of child health surveillance. Of the 145 (16%) not accepted, 57 (39%) had done an approved course and 71 (49%) had three or more years' experience. Respondents reported variable quality and availability of courses in child health. CONCLUSIONS: Acceptance of general practitioners on to child surveillance lists has not been carried out consistently despite national guidelines setting out criteria for acceptance. PMID- 1884062 TI - Family doctors and payment systems: the local option. PMID- 1884063 TI - The Royal College of Psychiatrists, 150 years on. PMID- 1884064 TI - Gas gangrene. PMID- 1884065 TI - A tax on infertility? PMID- 1884066 TI - Undergraduate medical education. PMID- 1884067 TI - Disillusion in medicine. PMID- 1884068 TI - Paper qualifications. PMID- 1884069 TI - Postgraduate medical examinations. PMID- 1884070 TI - Accelerated immunisation with diphtheria-tetanus-pertussis vaccine. PMID- 1884071 TI - Bleeding peptic ulcers. PMID- 1884072 TI - Helicobacter pylori infection and duodenal ulcer. PMID- 1884073 TI - Declining incidence of gastric cancer. PMID- 1884074 TI - Care of women with postnatal mental illness. PMID- 1884075 TI - Decompression sickness. PMID- 1884076 TI - What determines the age at the menopause? PMID- 1884077 TI - Zidovudine after occupational exposure to HIV. PMID- 1884078 TI - Africa's health. PMID- 1884079 TI - Doctors and the European Community. PMID- 1884080 TI - An intrapreneurial approach to integrating information production services into an academic medical center library. AB - The many challenges faced by health sciences libraries of all types and sizes often require innovative solutions. When an innovative solution involves calculated risk taking, the approach is called intrapreneurial. At the University of Miami School of Medicine, an intrapreneurial approach solved the fiscal problems of the biomedical communications unit. The Louis Calder Memorial Library inherited these problems when the Department of the Library and Biomedical Communications was created in the early 1980s. In this paper, two intrapreneurial programs are described, and the benefit and suitability of this management style to information services are demonstrated. PMID- 1884081 TI - The MAClinical Workstation Project at Georgetown University. AB - The intent of the MAClinical Workstation Project is to develop computer workstations for medical students of the sort they will use in future medical practice. The idea is to instill information query habits in the daily clinical activities of these young physicians-in-training. The Georgetown University Medical Center Library spearheads the project in conjunction with the School of Medicine. The library handles technical support, including software development, user training, equipment maintenance, and network installations. The project began in 1988 with nine Macintosh computers; today thirty machines are distributed throughout the Georgetown University Hospital conference rooms, faculty and resident offices, and at four affliated hospitals. The Macintosh computers are connected to the medical center's local area network (LAN) with access to the Integrated Academic Information Management System (IAIMS) and Library Information System (LIS) databases. The MAClinical workstations serve multiple educational purposes in the clinical setting. Primarily, students gain experience in medical informatics by using a variety of software systems installed at the stations: the H&P Writer, a history and physical system written in the C programming language, can be used by students to prepare the admission record on patients they examine; also, students can keep patient records, check findings against a diagnostic system, look up drugs and treatment protocols, develop medical sketches, and find additional information when needed in the medical literature. PMID- 1884082 TI - Currency of full-text medical journals: CCML and MEDIS vs. MEDLINE. AB - The authors ask whether full-text versions of medical journals are available for searching sooner than their biblographic counterparts. The journals in question are those found in the Comprehensive Core Medical Library (CCML) from BRS Information Technologies and in Mead Data Central's MEDIS Current Journal Files. All journals in these two files are full-text, and neither file contains any indexing features. Update schedules for the full-text version of the MEDLINE journals in each of these files were compared with the most recent issue available in the National Library of Medicine's (NLM) MEDLINE on five different dates. The data revealed substantial fluctuation in comparative currency for MEDIS/MEDLINE over the period of the test. On the date of the last snapshot, June 8, 1990, MEDLINE and MEDIS were offering the same currency for 43% of the journals, and MEDIS was providing first access to 29% of the titles. The CCML/MEDLINE comparison showed less variation. In the last snapshot MEDLINE and CCML were providing access to the same issue for 36% of the journals, and CCML was offering first access to 14%. Prior to publication, this paper was submitted to all three vendors for comment. Significant portions of their responses are quoted. PMID- 1884083 TI - The impact of economic issues on Nigerian health sciences libraries. AB - Economic issues are among the most important factors affecting health sciences libraries in Nigeria. These issues are influenced by the political, cultural, geographic, and demographic characteristics of the country. Significant economic issues are the dependence of the national economy on a single commodity, large foreign debt and spiraling inflation, stringent foreign exchange control measures, and inadequate realization by authorities of the role and importance of health sciences libraries. With shrinking budgets, resources, and staff, health sciences libraries can neither grow nor afford library automation. Health sciences librarians must take initiatives for cooperative activities to increase and make the most of resources, pursue nontraditional methods of fund-raising, educate authorities about the role and importance of libraries, and develop and implement a plan for the development and growth of health sciences libraries in the country. PMID- 1884084 TI - The establishment of an academic health sciences library in a developing country: a case study. AB - The development of a Faculty of Medical Sciences (FMS) and an academic health sciences library for the University of the West Indies (UWI) has proven to be a polemical and political issue due to the depressed economy of the country. Although FMS is still shrouded in politics and controversy after its inaugural year, the Medical Sciences Library (MSL) has expanded its dimensions and is actively developing a biomedical information network within the country. This will result in better dissemination and control of biomedical information. The library now participates in joint projects with other health sciences libraries in the country with the goal of joint automated listings of holdings and shared cataloging projects. This paper examines the development of the library and explains the difficulties experienced in its developmental stages due to politics, the delay in appointment of a medical sciences librarian, and the financial decline in the local economy. PMID- 1884085 TI - A comparison of biomedical databases. AB - Various published bibliographic and abstract services covering the period 1970 1988 were compared to analyze scope and coverage. A total of 7,281 articles and book titles (1,655 Soviet and 5,626 foreign) were selected on forty-one topics in different medical fields. The titles originated from three different samples but included all Soviet medical literature on the subjects. A distribution of biomedical serials from five databases is given by country, and twelve indices to assess the quality of biomedical databases are suggested. PMID- 1884086 TI - MELVYL MEDLINE: a library services perspective. AB - The MELVYL MEDLINE project resulted in the addition of a full five-year subset of MEDLINE to the University of California's (UC) MELVYL online union catalog. As one of the nation's largest MEDLINE end-user searching systems, MELVYL MEDLINE provides online bibliographic access to the biomedical journal literature for all UC personnel at over seventy library sites or by remote access. This paper summarizes the project's accomplishments, reports MELVYL MEDLINE use and its impact on library services, and provides insights for other end-user search systems. The project serves as a model for adding databases to the MELVYL catalog and demonstrates the potential for use by other disciplines of a specialized database when readily accessible. Evaluation results report high user satisfaction and high usage. However, many advanced searching features of the interface are little used by searchers. Effects on library services include marked increases in reference transactions and interlibrary loans, with significant declines in mediated search services. Future MELVYL MEDLINE enhancements include matching search retrievals to journal locations, linkage to an online document delivery system, and consideration of building a superset of databases by combining MELVYL MEDLINE with citations from another database in the MELVYL catalog. PMID- 1884087 TI - Creating and implementing an online patient education catalog. PMID- 1884088 TI - Twenty-four-hour access to a library collection. PMID- 1884089 TI - Soviet libraries in transition. PMID- 1884090 TI - Why authors fail. PMID- 1884091 TI - Richard A. Lyders Medical Library Association President 1991-1992. PMID- 1884093 TI - Effect of pertussis pretreatment on plasma glucose and insulin responses to lithium in rats. AB - 1. Administration of lithium to rats causes a rise in plasma glucose and suppresses glucose-stimulated insulin secretion. These effects are blocked by the alpha 2-adrenoceptor antagonist, yohimbine. 2. Pretreatment of rats with Bordetella pertussis toxin resulted in a reversal of the usual plasma glucose and insulin responses to intravenously administered lithium (4 mEq kg-1). There was a slow fall in plasma glucose, while plasma insulin rose to 267 +/- 42% (+/- s.e.mean) of control values at 30 min. The effect of lithium on glucose stimulated insulin secretion was also reversed; there was a marked increase in the insulin response which contrasted with the suppression seen in normal controls. 3. In perifused islets of Langerhans isolated from pertussis pretreated rats, the previously described inhibition by lithium of the second phase of glucose-stimulated insulin secretion from normal islets was almost completely abolished. 4. The results are consistent with the hypothesis that these effects of lithium are mediated by the influence of catecholamines on the islets. When the inhibitory effect of alpha 2-adrenoceptors is abolished by pertussis treatment, which blocks the action of the inhibitory guanine nucleotide-binding protein Gi, effects of beta-adrenoceptor stimulation predominate, leading to an increased secretion of insulin. PMID- 1884092 TI - Alkaline buffers release EDRF from bovine cultured aortic endothelial cells. AB - 1. Release of endothelium-derived relaxing factor (EDRF) and prostacyclin (PGI2) from bovine cultured aortic endothelial cells (EC) was measured by bioassay and radioimmunoassay, respectively. 2. Bradykinin (BK, 3-30 pmol), adenosine diphosphate (ADP, 2-6 nmol) or the sodium ionophore monensin (40-100 nmol) injected through a column of EC released EDRF. L-Arginine free base (FB; 10-20 mumol) or D-arginine FB (10-20 mumol) injected through the column of EC released similar amounts of EDRF and also caused an increase in pH of the Krebs solution perfusing the EC from 7.5-8.0 to 8.6-9.5. Sodium carbonate (Na2CO3) an alkaline buffer which caused the same changes in the pH of the Krebs solution also induced the same release of EDRF. The hydrochloride salts of L- or D-arginine did not cause either release of EDRF when injected through the column of EC or increases in the pH of the Krebs solution. 3. Inhibitors of either diacylglycerol lipase (RHC 80267) or kinase (R59022) inhibited the release of EDRF induced by BK or ADP but potentiated the release induced by L-arginine FB, monensin (40-100 nmol) or alkaline buffer (Na2CO3). R59022 and RHC 80267 infused through the EC increased the basal release of EDRF. 4. When calcium chloride was omitted from the Krebs solution the release of EDRF induced by alkaline buffer (Na2CO3; pH 8.6-9.5) or L arginine FB (10-20 mumol) was selectively inhibited when compared to that induced by BK (3-30 pmol) or ADP (2-6 nmol). This inhibition was reversed when calcium (2.5 mM) was restored. 5. NG-monomethyl-L-arginine (NMMA; 30 microM) inhibited release of EDRF induced by BK (10-30 pmol) or alkaline buffers (Na2CO3 or D arginine FB; pH 8.6-9.5). This inhibition was partially reversed by L- but not D arginine FB or HCl (30-100 microM). 6. Prostacyclin was released when BK (10 pmol), ADP (2 nmol) or arachidonic acid (30 nmol) were injected through the column of EC. However, monensin (40 nmol) or alkaline buffers (pH 8.6-9.5) did not release detectable amounts of PGI2 as measured by radioimmunoassay for 6-oxo prostaglandin F1 alpha. 7. Thus alkalinisation of the external bathing solution can release EDRF from cultured EC by a mechanism which does not involve receptor activation and which depends on the presence of extracellular calcium. PMID- 1884094 TI - The effects of endothelin-1 and NG-nitro-L-arginine methyl ester on regional haemodynamics in conscious rats with streptozotocin-induced diabetes mellitus. AB - 1. Resting haemodynamic status and responses to endothelin-1 (0.0004, 0.04, 0.4 nmol kg-1) and NG-nitro-L-arginine methyl ester (L-NAME, 10 mg kg-1) were assessed in conscious, Wistar rats treated with streptozotocin (STZ) to induce diabetes mellitus, and in control animals treated with saline. 2. In the resting state, STZ-treated rats had a bradycardia relative to control animals (291 +/- 13 and 337 +/- 10 beats min-1, respectively), but mean arterial blood pressures were the same in the two groups (STZ-treated 109 +/- 3; control 114 +/- 4 mmHg). However, the STZ-treated rats had raised renal (105 +/- 9 units) and mesenteric (114 +/- 16 units) vascular conductances and reduced hindquarters vascular conductance (26 +/- 4 units) relative to control rats (renal, 80 +/- 6; mesenteric, 75 +/- 7; hindquarters, 37 +/- 3 units). 3. Increasing doses of endothelin-1 caused similar, early falls and subsequent rises in mean arterial blood pressures in both groups of rats. Although there were initial hindquarters vasodilatations with endothelin-1 that were not different in STZ-treated and control rats, there were subsequent renal and mesenteric vasoconstrictions that were greater in the former. Hence, the similar rises in mean arterial blood pressures must have been accompanied by a greater reduction in cardiac output in the STZ-treated rats. 4. L-NAME caused similar renal and mesenteric vasoconstrictions in control and STZ-treated rats, but there was a smaller pressor effect and an attenuated hindquarters vasoconstrictor response to L-NAME in STZ-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1884095 TI - Platelet-leukocyte interaction in adhesion to endothelial cells induced by platelet-activating factor in vitro. AB - 1. Platelet-activating factor (PAF, 10 nM) did not induce platelet adhesion to endothelial cells cultured in monolayer but it induced their adhesion to protein coated plastic. However, PAF induced a marked platelet adhesion to endothelial cells when polymorphonuclear leukocytes (PMNs) were present. Lyso-PAF had no effect. 2. Phase-contrast microscopic examination showed that single platelets rather than their aggregates adhered to the endothelial cell surface around aggregating and adhering PMNs. 3. Significant platelet adhesion was induced by PAF at concentrations higher that 0.01 nM with the maximal response at 10 nM. Platelet adhesion occurred within minutes after PAF addition, reaching a maximum approximately after 30 min. Platelet adhesion also occurred significantly at a PMN:platelet ratio of 1:800, and linearly up to 1:50. 4. The PAF-induced platelet adhesion was suppressed by three structurally unrelated PAF antagonists, WEB 2086, ONO 6240 and BN 52021, in a concentration-dependent manner. 5. PAF also increased PMN adhesion to endothelial cell monolayers, which was further augmented by the presence of platelets. 6. The present study demonstrates that PAF induces platelet adhesion to endothelial cells in vitro when PMNs are present and that there is a close interaction between platelets and PMNs in their adhesion to endothelial cells. The present study further suggests that PMNs could play a central role in platelet adhesion to vascular endothlium in certain pathological conditions. PMID- 1884096 TI - Human interleukin-1 induces a rapid relaxation of the rabbit isolated mesenteric artery. AB - 1. Strips of rabbit superior mesenteric artery, precontracted with phenylephrine, relaxed when exposed to human recombinant interleukin-1 (IL-1) of the alpha or beta types. The effect was observed within 10 min, was optimal 32 min after the application of the cytokines and concentration-dependent (12-290 pM). 2. IL-1 alpha and IL-1 beta were equipotent in relaxing the rabbit mesenteric artery. A synthetic fragment corresponding to IL-1 beta 163-171 was approximately one million fold less active than IL-1 beta. The tripeptide Lys-D-Pro-Thr, an analogue of IL-1 beta 193-195, was inactive as an antagonist of IL-1 beta on the preparation. 3. Indomethacin (2.8 microM) prevented or acutely reversed IL-1 induced relaxations in the rabbit mesenteric artery. Purified haemoglobin (10 microM) or the removal of endothelium had no effect on relaxations elicited by IL 1 beta. 4. The preparation exhibited some selectivity for IL-1 as recombinant human tumour necrosis factor-alpha (TNF-alpha), IL-2 or IL-6 failed to influence it. TNF-alpha was not synergistic with a subthreshold concentration of IL-1 beta. 5. Immunoreactive 6-keto-prostaglandin F1 alpha and prostaglandin E2 were increased in the bathing fluid of isolated mesenteric arteries exposed to IL-1 beta as compared to controls. 6. A supernatant of lipopolysaccharide-stimulated human monocytes produced a relaxation of the preparation with a profile similar to that produced with IL-1s and there was a good quantitative agreement between the extent of the relaxation and the enzyme immunoassay measurements of IL-1 alpha and IL-1 beta in the supernatant.Furthermore the relaxation of crude monocyte IL-i was prevented by preincubating with antibodies to IL-l alpha and IL 1 beta. This experiment illustrates the possible use of the preparation for bioassay of IL-1. 7. It is concluded that either form of IL-I relaxes the precontracted rabbit mesenteric artery by a prostaglandin-dependent, nitric oxide independent mechanism. The model is also useful for distinguishing the mechanism of IL-1-induced hypotension in vivo in rabbits. PMID- 1884097 TI - Maintenance of functional activity of human pulmonary arteries after cryopreservation. AB - 1. Human intrapulmonary arteries have been investigated in vitro in fresh tissue or after storage at -190 degrees C in foetal calf serum containing 1.8 M dimethyl sulphoxide. 2. After cryopreservation of the arteries, maximal contractile force was reduced to 76%. This was assessed by the responses (in g) to 10 nM of the thromboxane analogue, U 46619. 3. Constricting agonists such as noradrenaline, 5 hydroxytryptamine, histamine and U 46619 stimulated fresh and frozen/thawed arteries producing pD2 values similar to the respective values determined on fresh tissues. 4. Endothelium-independent relaxant responses of U 46619 precontracted arteries to prostacyclin (PGI2), aminophylline and papaverine were generally unchanged after storage. The same was true for relaxant response to the potassium channel activator P-1075 whereas the pD2 values for SDZ PCO 400, RP 49356 and cromakalim were somewhat diminished. 5. Nevertheless, a significant correlation was obtained when the apparent pD2 values for all agonists on fresh and frozen/thawed tissues were compared (P less than 0.001). 6. The evidence suggests that after cryopreservation of human intrapulmonary arteries at -190 degrees C, mechanisms of both contraction and relaxation are well-maintained. PMID- 1884098 TI - Blockade by the local anaesthetic, tetracaine, of desensitization of Ca-induced Ca release after muscarinic stimulation in smooth muscle. AB - 1. Desensitization of contractile responses dependent on release of intracellularly stored Ca elicited by carbachol, histamine or caffeine was measured after desensitizing treatment with carbachol or histamine in the presence or absence of local anaesthetics in Ca-free solution containing 2 mM EGTA in the smooth muscle of guinea-pig taenia caecum. 2. Histamine-induced homologous desensitization was inhibited by tetracaine and procainamide. Dibucaine did not exert an inhibitory effect on the desensitization. This is consistent with our previous findings concerning the effects of local anaesthetics on the desensitization of histamine H1-receptors measured under normal physiological conditions. 3. Carbachol induced a functional change of intracellular Ca stores which resulted in heterologous desensitization. Tetracaine completely blocked carbachol-induced desensitization of the caffeine elicited contraction, but in the case of carbachol-induced desensitization of carbachol- and histamine-elicited contractions, this blocking effect of tetracaine was very weak and absent, respectively. The other local anaesthetics used did not affect the desensitization. These results suggest that the Ca induced and inositol trisphosphate-induced Ca release mechanisms were both desensitized by carbachol and that the desensitization of the Ca-induced Ca release mechanism was selectively blocked by tetracaine. PMID- 1884100 TI - Prejunctional modulatory action of neuropeptide Y on responses due to antidromic activation of peripheral terminals of capsaicin-sensitive sensory nerves in the isolated guinea-pig ileum. AB - 1. The effect of neuropeptide Y (NPY) on motor responses produced by activation of capsaicin-sensitive primary afferents in the guinea-pig isolated ileum was determined by use of capsaicin itself and electrical mesenteric nerve stimulation as stimuli. 2. NPY inhibited or suppressed the cholinergic contractile response produced by electrical mesenteric nerve stimulation while leaving the contractile response to a threshold concentration of capsaicin. 3. NPY had no effect on motor responses produced by a submaximal concentration of substance P, the putative endogenous mediator of the 'efferent' function of sensory fibres in this preparation. 4. It is concluded that NPY exerted a prejunctional inhibitory action on transmitter release from peripheral endings of capsaicin-sensitive nerves at interneuronal synapses. PMID- 1884099 TI - Endothelial modulation and changes in endothelin pressor activity during hypoxia in the rat isolated perfused superior mesenteric arterial bed. AB - 1. The isolated superior mesenteric arterial bed of the rat, perfused with Krebs Henseleit solution containing 10 microM indomethacin, was used to study the effects of reducing dissolved O2 tension on the pressor responses to endothelin 1, endothelin-3 and sarafotoxin S6b. The modulation of these responses by the endothelium was investigated by removing the intima with the detergent CHAPS and, for endothelin-1, by inhibiting nitric oxide production with N omega-nitro-L arginine methyl ester (L-NAME). Comparison was made with the effects of lowering O2 tension on the pressor responses to noradrenaline and 5-hydroxytryptamine. 2. Lowering the perfusate O2 tension from 551 +/- 2 mmHg to 14.0 +/- 0.5 mmHg did not change the ED50 for endothelin-1 but its maximal responses (Rmax) were increased by 2.1 and 2.7 fold, respectively, in the presence and absence of endothelium. The Rmax values for endothelin-3 were also greater in hypoxia either in the presence (by 2.3 fold) or absence of the endothelium (by 1.6 times) but those for sarafotoxin S6b were only enhanced significantly by hypoxia in the absence of the intima. hypoxia reduced the potencies of endothelin-3 and sarafotoxin S6b whether or not endothelium was present. 3. Endothelial destruction, whether in hypoxic or oxygenated conditions, increased the Rmax values for endothelin-1 and endothelin-3; at both O2 tensions those for endothelin-3 increased more than those for endothelin-1. The ED50 for endothelin 1 was unchanged by destroying the endothelium but endothelin-3 was less potent in the absence of an endothelium than in its presence. Removal of the endothelium did not change the R.ax for sarafotoxin S6b but increased its potency in both hypoxic and oxygenated tissues. 4. In hypoxia, and in the presence of both the endothelium and 100 microM L-NAME, the Rmax for endothelin-1 was 1.6 times greater than that in hypoxia in the absence of L-NAME. Co-infusion of 100 microM L-arginine, but not of 100 mircoM D-arginine, with 100 microM L-NAME reversed this effect. The presence of L-NAME decreased the potency of endothelin-1. 5. Destroying the endothelium did not affect the Rmax for noradrenaline in either oxygenated conditions or hypoxia. Changing 02 tension when the endothelium was intact had no effect on the Rmax but it was 11% greater in oxygenated, than in hypoxic, endothelium denuded preparations. Endothelial destruction decreased the potency of noradrenaline in hypoxia but increased it in oxygenated tissues. In hypoxia, L-NAME had no effect on the ED50 relative to control preparations with endothelium but the Rmax was 30% greater. 6. 5-Hydroxytryptamine gave very small pressor responses in the presence of endothelium in both oxygenated and hypoxic tissues but the Rmax was 1.7 times greater in hypoxia. L-NAME increased the R,,x by 9.8 times in oxygenated preparations and 6.3 fold in hypoxia. The ED5o values were the same in all conditions. 7. It is concluded that, although hypoxia generally increased the R.. for the endothelin/sarafotoxin peptides, the changes could not be explained by a simple increase in receptor number since hypoxia decreased the potency of endothelin-3 and sarafotoxin S6b. Thus alterations in receptor binding or activation properties, or both, also occurred. The changes associated with hypoxia were not common to all vasoconstrictor agonists since, in the absence of endothelial function, hypoxia did not affect the Rmax values for either noradrenaline or 5-hydroxytryptamine. Also, the pressor responses to the peptides and both the amines can be modulated by the endothelium in hypoxia as well as in oxygenated conditions. PMID- 1884101 TI - Effects of propafenone on 45Ca movements and contractile responses in vascular smooth muscle. AB - 1. In rat isolated aorta the class Ic antiarrhythmic drug, propafenone, dose dependently inhibited the contractile responses induced by high K (80 mM) and noradrenaline (NA, 10(-5) M), the IC50s being 2.5 +/- 0.7 x 10(-6) M and 8.7 +/- 0.8 x 10(-6) M, respectively. These inhibitory actions were also observed with propafenone added after the induced contractions. 2. Contractile responses induced by addition of Ca to 0 Ca high-K solution were also inhibited by propafenone (IC50 = 2.5 +/- 0.8 x 10(-6) M). Moreover, propafenone inhibited the contractile responses elicited by NA in strips incubated in 0 Ca (IC50 = 1.9 +/- 0.9 x 10(-6) M). 3. Propafenone also inhibited (IC50 = 1.2 +/- 0.4 x 10(-5) M) the development of spontaneous mechanical activity in portal vein segments. 4. Propafenone, 5 x 10(-6) M and 10(-5) M, inhibited 45Ca uptake stimulated by high K or NA without altering 45Ca uptake in resting strips. 5. These results indicated that in rat isolated aortae and portal veins propafenone inhibited Ca entry through voltage-operated channels and NA-induced Ca uptake as well as Ca release from intracellular stores. As a consequence it would reduce the concentration of intracellular free Ca available at the contractile apparatus for vascular smooth muscle contraction. PMID- 1884102 TI - IgE-dependent activation of alveolar macrophages augments neurally mediated contraction of small airways. AB - 1. We studied the effect of immunologically activated pulmonary alveolar macrophages (PAM) on functions of canine bronchiolar smooth muscle under isometric conditions in vitro. 2. PAM, stimulated with monoclonal anti dinitrophenyl (DNP) IgE antibody and DNP-human serum albumin (DNP-HSA), augmented the contractile responses of bronchioles to electrical field stimulation, whereas PAM treated with IgE antibody alone had no effect. 3. In contrast, the contractile responses to exogenously administered acetylcholine were not influenced by immunologically activated PAM. 4. The PAM-induced increase in the contractile responses to field stimulation was inhibited by pretreatment of PAM with indomethacin and by addition of the thromboxane A2 (TxA2) receptor antagonist SQ 29548. 5. The release of TxA2 from PAM was increased by anti-DNP IgE and DNP-HSA, an effect that was prevented by indomethacin. 6. These results suggest that PAM may play a role in the development of antigen-induced hyperreactivity of small airways through an IgE-dependent release of TxA2 which potentiates prejunctionally the parasympathetic component of bronchiolar smooth muscle tone. PMID- 1884103 TI - Epithelium-dependent potentiation of anaphylactic contractions by beta-endorphin in tracheae isolated from actively sensitized guinea-pigs. AB - 1. It has been shown that opioid peptides modulate airway function. In the present study, the effect of beta-endorphin on antigen-induced contractions of isolated tracheal rings from actively sensitized guinea-pigs has been studied. 2. beta-Endorphin had a concentration-dependent bimodal effect on anaphylactic contractions of the trachea. Low concentrations of beta-endorphin (10(-10) and 10(-8) M) significantly potentiated anaphylactic contractions, whereas higher concentrations (10(-7) and 10(-6) M) significantly suppressed anaphylactic contractions of guinea-pig trachea. 3. beta-Endorphin in concentrations of 10(-8) M and 10(-7) M did not affect the responsiveness of the tracheal rings to histamine or leukotriene D4. This indicates that beta-endorphin does not influence the responsiveness of tracheal smooth muscle to anaphylactic mediators. 4. In the presence of the non-selective opioid receptor antagonist naloxone, 10( 8) M beta-endorphin still potentiated the anaphylactic contractions of the trachea. In addition, an equimolar concentration of des-Tyr1-beta-endorphin, a fragment of beta-endorphin without opioid-like activity, also potentiated anaphylactic contractions. The potentiation of anaphylactic contraction by 10(-8) M beta-endorphin is not therefore mediated by classical opioid-receptors. 5. In the presence of naloxone, 10(-7) M, beta-endorphin did not suppress anaphylactic contractions of the trachea. Thus, the suppression of anaphylactic contraction is mediated via a classical opioid-receptor. 6. In epithelium-denuded trachea, both 10(-8) and 10(-7) M beta-endorphin suppressed the anaphylactic contractions, whereas 10(-8) and 10(-7) M des-Tyr1-beta-endorphin did not affect anaphylactic contractions. It is concluded that the potentiation of the anaphylactic contraction in intact trachea is epithelium-dependent whereas the suppression of the anaphylactic contraction is epithelium-independent. PMID- 1884105 TI - Regional haemodynamic effects of prolonged infusions of human alpha-calcitonin gene-related peptide in conscious, Long Evans rats. AB - 1. Haemodynamic measurements were made in conscious, Long Evans rats chronically instrumented for the assessment of changes in regional blood flows (renal, mesenteric and hindquarters, or internal and common carotid) and systemic arterial blood pressure and heart rate, before, during and after 3 day infusions of vehicle or human alpha-calcitonin gene-related peptide (CGRP) (1.5 or 15 nmol kg-1 h-1). 2. In animals with renal, mesenteric and hindquarters flow probes (n = 8), during the first day of infusion of human alpha-CGRP (1.5 nmol kg-1 h-1) there was sustained tachycardia and hypotension, a sustained reduction in renal flow, a transient reduction in mesenteric flow and a relatively well-maintained increase in hindquarters flow. All these effects were significantly different from the changes seen in vehicle-infused rats (n = 8), but calculation of vascular conductances showed only the late mesenteric vasodilatation and the sustained hindquarters vasodilatation were different from the changes in vehicle infused rats. However, by the second day of infusion and thereafter cardiovascular variables in the animals receiving vehicle and those receiving human alpha-CGRP were not different. 3. Nine animals instrumented with probes to monitor changes in internal and common carotid haemodynamics initially received human alpha-CGRP infused at a rate of 1.5 nmol kg-1 h-1. Three of these animals still showed some response to the human alpha-CGRP (tachycardia, hypotension, hyperaemic vasodilatation) throughout the second day of infusion and hence were taken through the 3 day infusion protocol. When the infusion was stopped on the fourth day all these animals showed reversal of the effects of human alpha-CGRP. 4. The results indicate substantial inter-individual variation in the haemodynamic effects of prolonged infusions of human alpha-CGRP in conscious, Long Evans rats. However, since increasing the dose of human alpha-CGRP overcame the desensitization, it is feasible that, in the clinical setting, maintained increases in internal carotid blood flow could be achieved by individually adjusted infusions of human alpha-CGRP. PMID- 1884104 TI - Differential effects of (+/-)-dobutamine and human alpha-CGRP on cardiac and on regional haemodynamics in conscious Long Evans rats. AB - 1. Comparisons were made of the full haemodynamic profiles of the known cardiostimulant, (+/-)-dobutamine, and the putative inotropic peptide, human alpha-calcitonin gene-related peptide (human alpha-CGRP), in conscious, chronically-instrumented Long Evans rats. Both substances were administered continuously i.v. for 60 min at two doses ((+/-)-dobutamine, 2 and 10 mumol kg-1 h-1; human alpha-CGRP, 0.15 and 1.5 nmol kg-1 h-1). 2. In spite of their similar (small) effects on mean arterial blood pressure, the low doses of (+/-) dobutamine and human alpha-CGRP influenced cardiac haemodynamics differently. Thus, (+/-)-dobutamine caused an increase in cardiac index (due to a tachycardia), accompanied by rises in peak aortic flow, maximum rate of rise of aortic flow (dF/dtmax) and total peripheral conductance. However, the latter waned during the infusion, and after the infusion there was a significant systemic vasoconstriction and reductions in peak aortic flow, dF/dtmax and stroke index. Such 'off' effects following dobutamine infusion have not been described previously. The infusion of the lower dose of human alpha-CGRP caused only a transient fall in central venous pressure. 3. The rise in total peripheral conductance during infusion of the lower dose of (+/-)-dobutamine was associated with increases in hindquarters and common and internal carotid vascular conductances. The fall in total peripheral conductance after infusion was associated with renal vasoconstriction. Although there was no significant change in total peripheral conductance during the infusion of the lower dose of human alpha-CGRP there were hindquarters and carotid vasodilatations together with mesenteric vasoconstriction. 4. Infusion of the higher dose of ( )-dobutamine had greater effects than the lower dose on all cardiac haemodynamic variables and additionally, increased stroke index. However, the negative cardiac haemodynamic effects following the offset of infusion were also enhanced in association with marked renal and mesenteric vasoconstrictions. While infusion of the higher dose of human alpha-CGRP increased cardiac index, peak aortic flow, dF/dtmax and total peripheral conductance, stroke index fell together with central venous pressure. 5. (+/-)-Dobutamine caused greater cardiostimulation and increases in hindquarters blood flow than did human alpha-CGRP. However, the latter at the higher dose caused substantially greater common and internal carotid hyperaemia than did (+/-)-dobutamine, possibly indicating a selective and additional effect of human alpha-CGRP on cranial blood flow. Furthermore, there were no adverse cardiovascular effects following infusion of human alpha-CGRP. PMID- 1884106 TI - Time-dependent synergistic interactions between the vasodilator neuropeptide, calcitonin gene-related peptide (CGRP) and mediators of inflammation. AB - 1. The action of the long lasting neuropeptide vasodilator, calcitonin gene related peptide (CGRP), in potentiating oedema formation and neutrophil accumulation was investigated in the dorsal skin of the rabbit, in vivo. Combinations of agents under test were administered by intradermal (i.d.) injection. Oedema formation and neutrophil accumulation were then measured by quantitative radiolabel techniques. 2. CGRP (1 x 10(-11) mol per site) potentiated neutrophil accumulation induced by zymosan activated plasma, (used as a source of C5a des Arg), N-formyl-methionyl-leucyl-phenylalanine (FMLP) and leukotriene B4 (LTB4). In contrast CGRP did not induce neutrophil accumulation when injected alone. 3. Oedema formation induced by a series of chemically distinct mediators of increased microvascular permeability; bradykinin, platelet activating factor (PAF), FMLP and zymosan-activated plasma; measured 0-30 min after i.d. injection was potentiated by CGRP (1 x 10(-11) mol per site). 4. Oedema formation induced by zymosan activated plasma and FMLP but not bradykinin and PAF, was also significantly potentiated by CGRP when oedema was measured 30 60 min after i.d. injection. The potentiation of oedema induced by zymosan activated plasma measured 30-60 min after i.d. injection was not observed in the presence of the shorter acting prostanoid vasodilator prostacyclin (PGI2, 3 x 10( 10) mol per site). 5. These results suggest that CGRP, as a consequence of its sustained vasodilator activity could have prolonged potentiating effects on neutrophil accumulation and oedema formation in inflammatory conditions. PMID- 1884107 TI - Mechanical responses to catecholamines in the longitudinal muscle of guinea-pig gastric fundus. AB - 1. In the longitudinal muscle of guinea-pig gastric fundus, adrenaline and phenylephrine (1-30 microM) both produced a slow contraction preceded by a relaxation. The slow contraction was strongly inhibited by prazosin (0.1 microM), but only weakly by yohimbine (1 microM), suggesting main contribution of alpha 1 adrenoceptors. 2. Most of the slow contraction was blocked by meclofenamate or indomethacin (0.1-0.3 microM). Both these drugs also inhibited spontaneously generated muscle tone. In some preparations, obtained from the apical fundus, a small contraction remained in the presence of meclofenamate. 3. During contraction induced by prostaglandin E2, adrenaline produced sustained relaxation and phenylephrine often transient relaxation, in the presence of meclofenamate. The transient relaxation, but not the sustained relaxation, was suppressed by prazosin. 4. In the presence of prostaglandin E2 (5 nM), after treating with phenoxybenzamine (30 microM) for 30 min, isoprenaline and adrenaline produced concentration-dependent relaxation, with IC50 s of 3.9 nM and 64 nM, respectively. Propranolol shifted these concentration-response curves to the right, with apparent pA2 s of 8.15 and 7.34, respectively. 5. It is suggested that in the fundic longitudinal muscle, adrenaline-induced contraction is mediated mainly by an increase in endogenous prostaglandin production through activation of alpha 1-adrenoceptors and that adrenaline produces transient relaxation through alpha 1-adrenoceptors and sustained relaxation through beta adrenoceptors. The beta-adrenoceptors in the longitudinal muscle are more sensitive to adrenaline and isoprenaline than those in the circular muscle. PMID- 1884108 TI - Renal handling and effects of S(+)-ibuprofen and R(-)-ibuprofen in the rat isolated perfused kidney. AB - 1. The renal handling and effects of S(+)- and R(-)-ibuprofen have been studied in the isolated perfused kidney (IPK) of the rat. 2. Both ibuprofen enantiomers were extensively reabsorbed and accumulated in the kidney in a concentration dependent manner. No pharmacokinetic differences were observed between the two enantiomers. 3. S(+)-ibuprofen concentrations ranging from 0.25 to 25 micrograms ml-1 (1.2 to 120 microM) caused a decrease in urinary flow, glomerular filtration rate (GFR) and electrolyte excretion. Urinary pH and excretion of glucose were not influenced. R(-)-ibuprofen concentrations ranging from 2.5 to 25 micrograms ml-1 (12 to 120 microM) also decreased urinary flow and electrolyte excretion. This decrease, however, was less than observed with S(+)-ibuprofen. GFR, urinary pH and glucose excretion were not affected by R(-)-ibuprofen. Prostaglandin E2 (PGE2) concentrations of 133 ng ml-1 reversed the effects on renal function of both enantiomers. 4. Very high S(+)- and R(-)-ibuprofen concentrations (greater than 400 micrograms ml-1) resulted in an increase in urinary flow and fractional excretion of sodium, chloride, potassium, glucose and calcium. 5. It is concluded that the pharmacokinetic behaviour of ibuprofen in the kidney is not stereoselective. Relatively high concentrations of both enantiomers increased the urinary flow and electrolyte excretion in a nonstereoselective manner. Lower concentrations of S(+)-ibuprofen decreased urinary flow and electrolyte excretion. The pharmacologically inactive R(-)-ibuprofen was also able to affect renal function in a similar way, but at different concentrations. These effects on renal function are probably caused by inhibition of PGE2 synthesis. PMID- 1884109 TI - Effects of midaglizole, a new hypoglycaemic drug on the electrophysiological properties of guinea-pig papillary muscle. AB - 1. The electrophysiological effects of midaglizole, a new oral hypoglycaemic agent which is an alpha 2-adrenoceptor antagonist, were assessed in the reserpinized ventricular myocardium of the guinea-pig. 2. Midaglizole suppressed the maximal rate of rise (Vmax) and the amplitude of action potentials (APA) of the fast and the slow responses in a concentration-dependent manner without influencing the resting potentials. 3. Voltage-dependency of the Vmax block of the action potentials by midaglizole (10 microM) did not appear in solutions containing various concentrations of KCl. 4. It is concluded that midaglizole has inhibitory effects on the fast Na+ and slow Ca2+ currents of the membrane independent of the blockade of myocardial alpha-adrenoceptors, and that these effects may be significant in some clinical uses of the drug. PMID- 1884110 TI - Modulation of the structure-binding relationships of antagonists for muscarinic acetylcholine receptor subtypes. AB - 1. Membranes from rat cerebral cortex, myocardium and extraorbital lacrimal gland were used as sources of M1, M2 and M3 muscarinic acetylcholine receptors respectively and the affinities of seven antagonists for the three subtypes were examined under different experimental conditions. 2. The affinities for the membrane-bound receptors were measured at different ionic strengths and temperatures and compared with those determined on the receptor solubilised in the neutral detergent digitonin or the zwitterionic detergent, CHAPSO. 3. The range of measured affinity constants of a given antagonist for a specific subtype varied from 2 (atropine at M1 receptors) to 1000 (AF-DX 116 at M2 receptors). 4. As a consequence of these changes in affinity, which were dependent on the drug, the subtype and the experimental conditions, both the structure-binding relationships of a given subtype can be markedly changed as well as the selectivity of a drug for the different subtypes. For example it is possible to change the relative affinities of AF-DX 116 and gallamine at membrane-bound M1 receptors from 50:1 to 1:60. 5. Experimental conditions for the observation of high selectivity of pirenzepine, AF-DX 116, gallamine and hexahydrosiladiphenidol for the three subtypes are given. 6. When the receptors are removed from their membrane environment by solubilisation in detergent, antagonist affinities are changed but the subtypes still retain different structure-binding relationships. 7. In general, AF-DX 116 and the allosteric antagonist, gallamine, behave differently from the other antagonists, suggesting that they bind in different ways to muscarinic receptors. Careful attention should therefore be paid to the experimental conditions in binding assays used to assess the affinities and selectivities of new muscarinic antagonists in order to avoid misleading results. 9. The ability to produce enhanced or attenuated affinities and selectivities of antagonists, resulting from the induction of different conformations of the receptor by a variety of physical, chemical or molecular biological perturbations may lead to a better understanding of the structural basis of drug receptor interactions. PMID- 1884111 TI - Rate and concentration-dependent effects of UK-68,798, a potent new class III antiarrhythmic, on canine Purkinje fibre action potential duration and Vmax. AB - 1. The frequency-dependent electrophysiological effects of UK-68,798 in concentrations of 1, 3, 10 and 30 nM were examined in isolated cardiac Purkinje fibres of the dog at both a number of constant rates of stimulation and following abrupt changes in pacing cycle length. 2. In all concentrations evaluated, UK 68,798 lengthened action potential duration in a concentration- and rate dependent manner (e.g., at a cycle length = 500 ms, control APD90 = 234.0 +/- 3.3 ms, while after 10 nM UK-68,798, APD90 = 315.0 +/- 5.9 ms). 3. The duration of action potentials evoked following abrupt changes in pacing rate were also increased in a concentration-dependent manner at all diastolic intervals tested. 4. The fast and slow time constants for restitution of APD were not altered by UK 68,798. However, the amplitude terms for this relation were increased. 5. In addition, the maximum upstroke velocity (Vmax) was not significantly affected by exposure to UK-68,798 at any concentration or diastolic interval. The kinetics for recovery of Vmax were thus unaffected. 6. These findings are similar to those previously reported for recognized class III antiarrhythmic agents (e.g., bretylium, clofilium, and sotalol); however, UK-68,798 was 1,000 to 10,000 times more potent. 7. The combined potency and selectivity of this agent seem to make it an ideal tool for the investigation of cardiac potassium channels believed responsible for controlling the duration of the action potential. 8. This potent and highly selective compound may prove extremely useful in the control of cardiac arrhythmias. PMID- 1884112 TI - Cardiac haemodynamic effects of the non-peptide, angiotensin II-receptor antagonist, DuP 753, in conscious Long Evans and Brattleboro rats. AB - 1. In previous experiments in conscious, water-replete Long Evans and Brattleboro rats the non-peptide angiotensin II-receptor antagonist, DuP 753, caused only slight hypotension and peripheral (particularly renal) vasodilatations. However in water-deprived (i.e. renin-dependent) Brattleboro rats, DuP 753 caused marked hypotension and regional vasodilatations. The major objective of the present study was to determine if the hypotensive effects of DuP 753 under any of the experimental conditions studied previously were contributed to by negative effects on cardiac haemodynamics. 2. Male, Long Evans and Brattleboro rats were chronically instrumented with electromagnetic flow probes on the ascending aorta and with intravascular catheters. Data were collected by use of a microcomputer based system that provided digitised print-out of instantaneous heart rate, mean arterial blood pressure, cardiac output, stroke volume, peak aortic flow, maximum positive slope of the aortic flow signal (+ dF/dtmax), total peripheral conductance and central venous pressure. 3. Incremental i.v. bolus doses (0.1-10 mg kg-1, at 15 min intervals) of DuP 753 were administered to water-replete Long Evans (n = 8) and Brattleboro (n = 8) rats, and to water-deprived (14 h) Brattleboro rats (n = 9) (the latter animals show marked activation of the renin angiotensin system). In all groups, 15 min after the highest dose of DuP 753 had been given, a supramaximal dose of captopril (2 mg kg-1) was injected to determine if it had any additional effects. 4. In water-replete, Long Evans and Brattleboro rats, DuP 753 (0.1-1 mg kg-1) caused slight, transient hypotension, with rises in total peripheral conductance; increases in cardiac output, peak aortic flow, + dF/dtmax and stroke volume were inconsistent and central venous pressure did not change. Higher doses of DuP 753 (3 and 10mgkg-') caused modest, sustained hypotension that was due entirely to an increase in total peripheral conductance, since cardiac output, peak aortic flow and + dF/dtmax showed transient elevations; captopril had no additional hypotensive or vasodilator effects. 5. Under resting conditions, water-deprived Brattleboro rats showed an increase in mean arterial blood pressure, but there were reductions in total peripheral conductance, cardiac output and + dF/dtmax. DuP 753 (0.1-10 mg kg- 1, i.v., boluses at 15 min intervals) caused incremental hypotension and tachycardia and dose-dependent rises in total peripheral conductance that were accompanied by transient increases in cardiac output, peak aortic flow and + dF/dtmax; captopril had no additional hypotensive or vasodilator effects. 6. Under no conditions were there any negative effects of DuP 753 on myocardial function; moreover, it is likely the transient increases in cardiac function following DuP 753 were indirect and due to the reduction in afterload. Thus, it appears the haemodynamic effects of DuP 753 can be explained by its vasodilator action. PMID- 1884113 TI - A quantitative investigation into the dependence of Ca2+ mobilisation on changes in inositol 1,4,5-trisphosphate levels in the stimulated neutrophil. AB - 1. The coupling of N-formyl-methionyl-leucyl-phenylalanine (fMet-Leu-Phe) receptor stimulation to Ca2+ mobilisation has been investigated in the human neutrophil by measuring the concentration-effect curves for inositol 1,4,5 trisphosphate (IP3) formation and Ca2+ mobilisation. 2. fMet-Leu-Phe-dependent mobilisation of intracellular Ca2+ has been monitored in fluo-3-loaded human neutrophils by measuring increases in the cytoplasmic free Ca2+ concentration ([Ca2+]i) in the presence of extracellular EGTA. Fluo-3 was used in preference to fura-2 because it was found to be more sensitive to the high Ca2+ levels seen in stimulated neutrophils. 3. fMet-Leu-Phe induced a rapid mobilisation of intracellular Ca2+ (EC50 = 2.9 +/- 0.1 nM) and increased [Ca2+]i to a maximum of 1286 +/- 184 nM. 4. The amount of IP3 in fMet-Leu-Phe-stimulated neutrophils was determined by competition with [3H]-IP3 for a specific IP3 binding protein isolated from bovine adrenocortical microsomes. Basal IP3 levels of 13.3 +/- 2.0 pmol per 10(7) cells were increased nearly 4 fold by maximally effective concentrations of fMet-Leu-Phe. 5. The EC50 for the IP3 response (95 +/- 18 nM) was much higher than that for mobilisation of intracellular Ca2+, such that only a doubling in the concentration of IP3 was required to fully mobilise intracellular Ca2+. 6. As a result of this relationship IP3 production was more sensitive than Ca2+ mobilisation to inhibition by demethoxyviridin, an inhibitor of phospholipase activation. PMID- 1884114 TI - The effect of drugs acting on cholinoceptors and mucosal chloride on luminal bicarbonate transport by rat caecum under in vitro conditions. AB - 1. The transport of HCO3- (Jsm) from a HCO3(-)-buffered serosal to an unbuffered mucosal saline solution has been studied in rat caecum in vitro. 2. Carbachol, bethanechol and acetylcholine (ACh) caused a concentration-dependent fall in Jsm with similar maximum effects. 1,1-Dimethyl-4-phenyl-piperazinium iodide (DMPP) also inhibited Jsm but the effect was less than with the other drugs. Maximum cholinoceptor inhibition was less than that obtained with anoxia. 3. Responses were blocked by atropine (10(-5) M) but hexamethonium (2 x 10(-4) M) significantly altered the response only to DMPP. 4. Physostigmine (10(-5) M) shifted the ACh response curve to the left but physostigmine itself caused inhibition of Jsm which was blocked by atropine. 5. Substitution of mucosal Cl- by NO3- reduced Jsm to a similar extent to maximum cholinoceptor effect and abolished responses to bethanecol. Anoxia further reduced Jsm in the presence of NO3-. 6. Mucosal SITS and DIDS (1 mM) reduced Jsm but this was less than the maximum inhibition seen with drugs acting on cholinoceptors or mucosal Cl- removal. Serosal DIDS caused a similar inhibition. 7. We conclude that cholinoceptor agonists inhibit but do not abolish luminal bicarbonate transport by an action on muscarinic receptors. PMID- 1884115 TI - Nitric oxide is the mediator of ATP-induced dilatation of the rabbit hepatic arterial vascular bed. AB - 1. Livers of 10 New Zealand White rabbits were perfused in vitro with Krebs Bulbring buffer via the hepatic artery (HA) and portal vein (PV) at constant flows of 23 +/- 1 and 77 +/- 1 ml min-1 100 g-1 respectively. The tone of the preparation was raised with noradrenaline (concentration: 10 microM). 2. Dose response curves for the vasodilatation produced by adenosine 5'-triphosphate (ATP), acetylcholine (ACh), adenosine, and sodium nitroprusside (SNP) were obtained following injection into the HA supply. Injections were then repeated in the presence of the L-arginine to nitric oxide pathway inhibitors N-monomethyl-L arginine (L-NMMA, n = 6) and N-nitro-L-arginine methyl ester (L-NAME, n = 4) at concentrations of 30 microM and 100 microM for each inhibitor. 3. Both L-NMMA and L-NAME antagonized the responses to ATP and ACh; L-NAME was 2-3 times more potent than L-NMMA as an inhibitor of these endothelium-dependent vasodilatations. Neither L-NMMA nor L-NAME attenuated responses of the endothelium-independent vasodilators, adenosine and SNP. 4. These results indicate that nitric oxide is the mediator of ATP-induced vasodilatation in the HA vascular bed of the rabbit and that the receptor responsible for the release of nitric oxide, the P2y purinoceptor, is located predominantly on the endothelium. PMID- 1884116 TI - Kinetics of (+)-tubocurarine blockade at the neuromuscular junction. AB - 1. Although (+)-tubocurarine (Tc) is classically considered to be a competitive antagonist at the neuromuscular junction, kinetic details of the interaction remain unclear. 2. We studied the competitive action of Tc on the nicotinic receptor at the frog neuromuscular junction using a quantitative analysis of the generation phase of miniature endplate currents (m.e.p.cs) recorded in Ringer solution (20 degrees C) under voltage clamp (-90 mV) in the absence or presence of 1-5 microM Tc. Under control conditions four neurotransmission parameters were estimated by non-linear regression using a mathematical model of synaptic transmission incorporating transmitter release, diffusion, hydrolysis, receptor binding and channel gating. These parameters were then used in a further regression to estimate binding rate constants for Tc at the same endplate. Allowance was made for open channel block by Tc, which under the conditions of this study was only a small component of total blockade. 3. The results suggest that Tc binds to the two agonist recognition sites on the nicotinic receptor with equal affinity (stoichiometric KDs of 2.2 and 8.8 microM), and that most of the functional blockade at concentrations up to 5 microM is due to occupancy of only one site. 4. The association rate constant for Tc binding to sites on the nicotinic acetylcholine receptor appears to be very fast (k+D = 8.9 x 10(8) M-1 s 1) and comparable to that for acetylcholine (ACh). 5. In the brief time during which an m.e.p.c. is generated (approximately 200 microseconds, reversal of Tc blockade by transiently high concentrations of ACh seems to be kinetically limited. PMID- 1884117 TI - The quantitative study of lumbar vertebral bone marrow using T1 mapping and image analysis techniques: methodology and preliminary results. AB - A method of quantifying lumbar vertebral bone marrow using pixel by pixel T1 mapping of spin echo magnetic resonance images is described. The accuracy and precision of the relaxation time measurements is confirmed by studies with the EEC Concerted Research Project, test object no. 5. The T1 data from all the pixels sampled from lumbar vertebral marrow are displayed as a histogram. By "thresholding" relative to normal control data the spatial distribution of high or low T1 pixels can be demonstrated. The approach is superior to that of the conventional region of interest method for quantifying and analysing relaxation time data, and allows tissue heterogeneity to be studied. Studies in patients with aplastic anaemia and acute leukaemia have been performed. PMID- 1884118 TI - Ultrasonic detection of parathyroid adenomas. AB - High-resolution real time sonography was used to evaluate patients with suspected primary hyperparathyroidism. A total of 12 consecutive patients was scanned pre operatively. The sensitivity of the procedure was 92% and the specificity 97%. In our hospital sonography is the procedure of choice for localizing enlarged parathyroid glands prior to surgical exploration. PMID- 1884119 TI - Magnetic resonance imaging in the staging of renal cell carcinoma. AB - A prospective study has been carried out to examine the role of magnetic resonance imaging (MRI) in the investigation of renal cell carcinoma in 24 patients. In all cases the inferior vena cava (IVC) was well demonstrated with MRI. In 14 out of 15 patients where surgical correlation was available, the MRI and operative staging were in agreement. Magnetic resonance imaging and computed tomographic (CT) staging were in agreement in 16 out of the 17 patients where both were performed. In one case, CT suggested hepatic invasion but this was found not to be present on MRI and at operation. Magnetic resonance imaging also provided substantial additional information in three patients, including two cases where MRI demonstrated a patent IVC that appeared occluded on CT (one of which also had vertebral metastases seen on MRI but missed on CT) and one case where CT failed to demonstrate minimal involvement of the IVC. Magnetic resonance imaging is an accurate means of staging renal cell carcinoma with clear advantages over CT. In no case in this series was inferior vena cavography found to be necessary. PMID- 1884120 TI - Embolization with steel coils using a saline flush technique. AB - A method using saline flush to push Gianturco steel coils through catheters is described, and has been successfully used in 45 patients. The saline flush technique requires no precise matching of coils and catheters, solves problems associated with the conventional method and simplifies the coil embolization procedure. PMID- 1884121 TI - Organ doses received by atomic bomb survivors during radiological examinations at the Radiation Effects Research Foundation. AB - When evaluating the risks of oncogenesis and cancer mortality following exposure to the radiations of the atomic bombs (A-bombs), the medical X-ray doses received by the A-bomb survivors must also be estimated and considered. Using a human phantom, dosimetry was performed to estimate the X-ray doses received by A-bomb survivors during medical examinations at the Radiation Effects Research Foundation (RERF) as part of the long-term follow-up on the Adult Health Study (AHS). These examinations have been estimated to represent nearly 45% of the survivors' cumulative medical irradiation dose. Doses to the salivary glands, thyroid gland, lung, breast, stomach and colon were measured using thermoluminescent dosimeters. The results, which are reported here, will aid in estimating organ doses received by individual AHS participants. PMID- 1884122 TI - Organ doses to atomic bomb survivors during photofluorography, fluoroscopy and computed tomography. AB - Doses to the salivary glands, thyroid gland, breast, lung, stomach and colon during mass radiological gastric screening, mass radiographic chest screening, upper gastrointestinal series and computed tomography were determined by exposing a female human phantom to simulated radiological X-ray examinations as performed in community hospitals. The doses were measured using thermoluminescent dosimeters, and the results will be used to document organ doses received by participants in the Atomic Bomb Casualty Commission/Radiation Effects Research Foundation Adult Health Study. PMID- 1884123 TI - Calibration of a Microselectron HDR iridium 192 source. AB - A method for the calibration of the output, in terms of an air kerma rate, of the high activity miniature iridium 192 sources used in the Microselectron HDR afterloading unit is described. An air kerma rate is measured using a calibrated thimble chamber in an "in-air" calibration jig. The results are compared with an air kerma rate derived from the manufacturer's test certificate. In some cases, the ionization chamber measurements have been followed by a further calibration check using thermoluminescent dosimetry. Other checks carried out when a new source is received are also briefly described. PMID- 1884124 TI - Response of the mouse mediastinum to single and fractionated X-rays. AB - The acute oesophageal response, after localized mediastinal irradiation in unanaesthetized mice, was assessed with a sequential, non-invasive and clinically orientated assay. Changes in body weight, after single and fractionated X-ray doses (8 fractions in 8 or 15 days and 4 fractions in 4 or 13 days), were recorded and the nadir of weight loss for each regime was used as the end-point. In our studies, quantal and non-quantal analyses of the weight loss data gave good dose-response relationships. The shapes of the dose-effect curves for single doses, 4F/4 days and 8F/8 days showed a remarkable degree of radioresistance, which became less apparent when the overall time was increased to 13 and 15 days for 4 and 8 fractions, respectively. The alpha/beta values (7-17 Gy) are within the range found for other acutely responding normal tissues. Histopathological changes were also assessed and the structural changes observed in the oesophageal epithelium, after a single dose of 34 Gy or after 46 Gy given as 3F/6 days, correlated with the gross changes observed in body weight. PMID- 1884125 TI - Development of video frame store and distortion correction facilities for an external-beam radiotherapy treatment simulator. PMID- 1884126 TI - An unusual cause of a pain in the calf. PMID- 1884127 TI - Unusual magnetic resonance findings in Wilson's disease. PMID- 1884128 TI - Demonstration on computed tomography of two pseudoaneurysms complicating chronic pancreatitis. PMID- 1884129 TI - Extensive calcification in the breast in chronic renal failure. PMID- 1884130 TI - Primary lymphoma of the urinary bladder. PMID- 1884131 TI - Body composition by intercomparison of underwater weighing, skinfold measurements and dual-photon absorptiometry. PMID- 1884132 TI - Effect of radiological iodinated contrast media on acetylcholinesterase activity. PMID- 1884133 TI - The significance of patient weight when comparing X-ray room performance against guideline levels of dose. PMID- 1884134 TI - Occupational exposure and the Central Index of Dose Information. PMID- 1884135 TI - Haemangioma of the urinary tract: review of the literature. AB - General features. Haemangiomas are benign vascular tumours. They can regress spontaneously as a result of fibrosclerosis, suggesting a conservative approach wherever possible. Asymptomatic haemangiomas do not require treatment. Renal haemangioma. In all, 198 cases have been reported. The lesion is usually solitary and unilateral and occurs most often in the pyramid, and in the mucosa or subepithelial tissue of the pelvis. In some cases a tentative diagnosis of haemangioma has been made by means of selective renal angiography and pre- or per operative renoscopy. Partial nephrectomy is recommended in cases of minor haemangioma. Ureteric haemangioma. Six cases have been described. When haemangioma is suspected a conservative operation is recommended. Bladder haemangioma. A total of 106 cases have been reported. Many of the tumours had the characteristics of an iceberg, with considerable extravesical extension making endoscopic management less suitable because of the possibility of massive haemorrhage or recurrence. Consequently, many authors prefer local excision. In the case of endoscopic treatment the patient should be prepared for open surgery. Urethral haemangioma. Twenty cases have been described. The lesions often extend further than is immediately apparent. Endoscopic management is recommended for small lesions and, in the case of more extensive lesions, open exploration is advised followed by appropriate urethral reconstruction. PMID- 1884136 TI - Staghorn calculi--long-term results of management. AB - We have treated 167 patients with staghorn calculi. Conservative therapy was used in 61 patients who have been followed up for 1 to 18 years (average 7.8). Chronic renal failure occurred in 22 of these patients and 7 died from uraemia. The causes of chronic renal failure were bilateral staghorn calculi, staghorn calculi and contralateral urinary calculi, and chronic pyelonephritis of the contralateral kidney. The morbidity and mortality rates following conservative treatment were higher than those following surgical management. The pathological findings in 47 kidneys after nephrectomy showed severe hydronephrosis, renal abscess and xanthogranulomatous pyelonephritis. These results indicated that staghorn calculi destroyed the kidney and early complete removal of these stones is advisable. PMID- 1884137 TI - Inhibition by sodium-potassium citrate (CG-120) of calcium oxalate crystal growth on to kidney stone fragments obtained from extracorporeal shock wave lithotripsy. AB - Retention of fragments within the kidney after extracorporeal shock wave lithotripsy (ESWL) continues to be a major shortcoming of this form of stone treatment. The aim of this study was to evaluate the ability of sodium-potassium citrate to inhibit calcium oxalate crystal nucleation and growth on to stone fragments remaining after ESWL. The continuous flow crystallisation technique was adapted to induce calcium oxalate crystal nucleation and growth on to the surface of fragmented kidney stones and the inhibitory effect of sodium-potassium citrate was assessed by scanning electron microscopy and by determining the relative increase in crystalline mass at final concentrations of 0, 2, 4, 6, 8, 10 mmol/l. Sodium-potassium citrate significantly inhibited the deposition of new crystalline calcium oxalate in a dose-dependent manner above 2 mmol/l; these findings were confirmed by scanning electron microscopy. It was concluded that sodium-potassium citrate may provide an effective means of preventing the formation of new kidney stones by the deposition of calcium oxalate on to residual stone fragments resulting from ESWL and that the technique used is an efficient means of testing the efficacy of therapeutic agents to prevent stone recurrence in patients treated with ESWL. PMID- 1884138 TI - A consumer's guide to commercially available urodynamic equipment. AB - Eight commercially available urodynamic machines from 6 major manufacturers (Aspen Medical, Dantec, Electro-Medical Supplies (EMS), Uro-gyn, Ormed and Wiest) were assessed for accuracy, construction and user-friendliness. There was less than 10% inaccuracy with regard to fill volume, void rate and pressure measurements. The Wiest 6000 plus system was between 11 and 14% inaccurate during voided volume measurement and other systems were less than 10% inaccurate. User friendliness was assessed during routine cystometry and is mainly dependent on the software supplied with the equipment. The merits and faults of each urodynamic system with regard to performing a urodynamic investigation, running a urodynamic service and data management are compared with an "ideal" urodynamic system. PMID- 1884139 TI - Single-increment dilatation for percutaneous renal surgery: an experimental study. AB - Renal nephrostomy track dilatation is an integral part of percutaneous renal surgery. The traditional method has employed sequential dilators of increasing size, or balloon dilatation. This study used a canine model to investigate the effects of single-increment renal track dilatation to 24 F and compares it with the conventional techniques. Single-increment dilatation proved to be a safe technique with minimal haemorrhage or parenchymal damage and healing at 6 weeks by a fine linear scar. It was as safe as conventional techniques. We believe this study proves that single-stage dilatation is a safe technique for use in humans. PMID- 1884140 TI - Ambulatory monitoring and electronic measurement of urinary leakage in the diagnosis of detrusor instability and incontinence. AB - The ability of conventional artificial filling urodynamic studies (CMG) and ambulatory monitoring during natural bladder filling (AM) to detect phasic detrusor activity (detrusor instability) and incontinence was studied in 52 patients suspected on clinical grounds of having bladder dysfunction, but in whom a CMG had not provided an adequate explanation of their symptoms. Detrusor instability (DI) was found on AM in 31 patients who were not unstable on conventional CMG using the criteria of the International Continence Society: DI was diagnosed on filling in 20 patients and on provocation in a further 11. Incontinence was demonstrated by electronic nappy testing in 23 patients: 13 had urge incontinence due to DI, 7 had genuine stress incontinence alone and 3 had both genuine stress incontinence and detrusor instability. Thus DI was diagnosed significantly more frequently by AM than by CMG. Ambulatory monitoring was more sensitive in the diagnosis of instability and incontinence and it may prove to be a valuable aid in the diagnosis of bladder dysfunction not detected during conventional cystometry. PMID- 1884141 TI - Conservative treatment of vesicovaginal fistulas by bladder drainage alone. AB - We describe 4 cases of conservative management of vesicovaginal fistulas occurring as a complication of abdominal and vaginal hysterectomy. In all cases treatment involved simple bladder drainage for periods ranging from 19 to 54 days. At follow-up all patients remained dry. Such spontaneous closure of vesicovaginal fistulas following adequate bladder drainage has not been previously reported. PMID- 1884142 TI - Cystoscopic suction diathermy for the treatment of superficial bladder tumours. AB - The treatment of superficial bladder tumours (Ta, T1) is a time-consuming exercise for urological surgeons and patients. A method of treating the tumours, whether primary or recurrent, by endoscopic suction diathermy has been developed. The technique significantly reduces the amount of tumour debris within the bladder during treatment as well as the amount of diathermy employed. By removing the free tumour cells in the irrigation fluid the risk of tumour cell implantation may be kept to a minimum. PMID- 1884143 TI - Results of Medical Research Council phase II study of low dose cisplatin and methotrexate in the primary treatment of locally advanced (T3 and T4) transitional cell carcinoma of the bladder. AB - A series of 49 previously untreated patients with category T3 or T4 bladder cancer underwent treatment with low dose methotrexate and cisplatin; 44 patients were eligible for assessment of response. Complete response (CR) was seen in 5 patients (11%) and partial response in 15 (34%) (overall response rate 45%). Treatment was reasonably well tolerated with no major morbidity and no treatment related deaths. After a median follow-up of 3.5 years, the 1-year and 2-year survival rates were 70 and 30% respectively. Ten patients remain recurrence-free without having received "definitive local therapy" (cystectomy and/or radiotherapy) at follow-up extending from 20 to 50 months. PMID- 1884144 TI - The value of ultrasound scanning of the upper urinary tract in patients with bladder outlet obstruction. AB - Ultrasound scanning of the upper urinary tract enables a urologist to allocate a degree of urgency for surgery when upper tract dilatation is present. We have studied whether other assessments of bladder outlet obstruction could eliminate this investigation. The study group comprised 223 consecutive patients who had ultrasound scans for bladder outlet obstruction. Estimation of urea, creatinine, residual urine and flow rate could not predict the presence of upper tract dilatation and it was concluded that ultrasound scanning of the upper tracts should continue to be used as a means of deciding how urgently a patient requires prostatic surgery. PMID- 1884145 TI - The sonographic appearance of irradiated prostate cancer. AB - Transrectal ultrasonography of the prostate was performed before radical prostatectomy in 22 patients with persistent or recurrent cancer after definitive radiotherapy. Serial transverse sonograms were compared with whole-mount step sections of the prostatectomy specimens to evaluate the sonographic features of irradiated prostate cancer. To define more clearly the effects of radiation on malignant prostatic tissue, we assessed the degree of histological change induced by the irradiation (radiation effects) as none, mild, moderate or severe. A total of 121 areas of cancer greater than 4 mm in maximum diameter were identified on the histological sections. Of these, 105 (87%) showed no radiation effects or mild effects, and 72% (76/105) of these appeared hypoechoic on the corresponding sonogram. There were 16 foci with moderate or severe radiation effects and only 25% (4/16) appeared hypoechoic. The remaining 12 foci were isoechoic. Areas of cancer which show moderate or severe radiation effects tend to become isoechoic while large (greater than 4 mm) foci of cancer in the irradiated prostate usually show little radiation effect, and these foci typically appear hypoechoic. PMID- 1884146 TI - Early endoscopic realignment of complete traumatic rupture of the posterior urethra. AB - Early primary endoscopic realignment of complete traumatic rupture of the posterior urethra is a simple, rapid and non-traumatic technique. We have recently treated 5 patients in this manner. All are continent and 4 are potent. Four patients were followed up for 1 year. One patient required no further management and had excellent urinary flow rates. The other 3 developed short secondary strictures which were managed successfully by 1 or 2 internal urethrotomies. PMID- 1884147 TI - Colour duplex sonography in the assessment of impotence. AB - We present our experience with colour duplex sonography (Acuson 128) in the assessment of 83 impotent men. Cavernosal artery measurements were taken before and after the intracorporeal injection of papaverine. The peak velocities following papaverine injection correlated well with the degree of clinical response. Percentage diameter change corresponded with some groups of clinical erection grade, although it was not as good a discriminator as peak velocity. Twelve patients with 24 cavernosal arteries were also examined using pharmacological selective arteriography. Correlation between duplex sonography and arteriography showed an accuracy of 87.5%, specificity of 100.0% and sensitivity of 82.4%. All patients with a clinically good response following papaverine injection had peak bilateral cavernosal artery velocities greater than or equal to 25 cm/s. Amongst the remaining suboptimal responders, 18 also had this finding. Fifteen of these underwent pharmacological cavernosography and 14 exhibited venous leakage. Duplex sonography is a valuable and non-invasive tool in the assessment of impotence and can provide valuable information in deciding the course of further evaluation and treatment. The procedure was always completed more quickly with the guidance of colour Doppler. PMID- 1884148 TI - Lord's procedure--the best operation for hydrocele? AB - A prospective study was carried out to compare Lord's hydrocele operation with traditional surgical procedures. The groups of patients investigated were comparable in terms of age, period of observation, number of previous aspirations and size of hydrocele. The incidence of isolated hydrocele of the spermatic cord, as well as epididymal cysts, was lower in the patients who underwent Lord's procedure (7.2 versus 15.8%), as was the percentage of patients reporting post operative pain for more than 3 days (4.3 versus 15.8%, p less than 0.05). PMID- 1884149 TI - Clinical patterns of paediatric urolithiasis. AB - A series of 270 paediatric stone patients was studied retrospectively according to the clinical pattern of urolithiasis (age and sex, stone location, stone analysis, recurrence rate) and aetiology of stone disease (infection, anatomical, metabolic or idiopathic). Infection stones occurred earliest and more commonly in males and were usually upper tract struvite calculi related to Proteus infection. Anatomical stones were most commonly associated with pelviureteric junction (PUJ) obstruction and had a high recurrence rate, despite surgical correction of obstruction. Idiopathic stones most resembled those found in adult urolithiasis by virtue of occurring latest, being sited in the ureter more often and being more frequently composed of calcium oxalate. Metabolic stones were most frequently calcium phosphate or cystine and virtually all were renal. They comprised the smallest group but had the highest recurrence rate. PMID- 1884150 TI - Acute scrotal pain in two brothers. PMID- 1884151 TI - Renal carbuncle presenting as acute peritonitis in pregnancy. PMID- 1884152 TI - Tuberculous cerebral abscess 8 years after renal transplantation. PMID- 1884154 TI - Multifocal ureteric amyloidosis. PMID- 1884153 TI - Actinomycotic vesico-uterine fistula from a wishbone pessary contraceptive device. PMID- 1884155 TI - Venous bypass and filtration during nephrectomy for renal carcinoma with tumour thrombus in the retrohepatic cava. PMID- 1884156 TI - Incidental renal carcinoma discovered during ultrasound localisation of renal calculi for extracorporeal piezoelectric lithotripsy. PMID- 1884157 TI - Oral trazodone in the treatment of total secondary impotence in a diabetic patient. PMID- 1884158 TI - Relationship between segmental arteries and pelviureteric junction. PMID- 1884159 TI - An aid to rigid ureteroscopy--stone basket. PMID- 1884160 TI - Stenting the extravesical ureteroneocystostomy in kidney transplantation. PMID- 1884161 TI - re: Comparison of primary orchiectomy and polyoestradiol phosphate in the treatment of advanced prostatic cancer. R. Haapiainen et al. Br. J. Urol., 66, 94 97, 1990. PMID- 1884162 TI - re: Bacteriological state of the urine in symptom-free adult males. I. D. Sugarman et al. Br. J. Urol., 66, 148-151, 1990. PMID- 1884163 TI - re: Ruptured bladder following circumcision using the Plastibell device. L.D. Jee and A.J.W. Millar. Br. J. Urol., 65, 216-217, 1990. PMID- 1884164 TI - re: Symptoms versus flow rates versus urodynamics in the selection of patients for prostatectomy. J. McLoughlin et al. Br. J. Urol., 66, 303-305, 1990. PMID- 1884165 TI - Simultanagnosia. To see but not two see. AB - Simultanagnosia is a disorder of visual perception characterized by the inability to interpret complex visual arrays despite preserved recognition of single objects. We report a series of investigations on a simultanagnosic patient which attempt to establish the nature of this visual processing disturbance. The patient performed normally on a feature detection task but was impaired on a test of attention-requiring visual search in which she was asked to distinguish between stimuli containing different numbers of targets. She was not impaired on a visual-spatial orienting task. She identified single briefly presented words and objects as rapidly and reliably as controls suggesting that access to stored structural descriptions was not impaired. With brief, simultaneous presentation of 2 words or drawings, she identified both stimuli significantly more frequently when the stimuli were semantically related than when they were unrelated. On the basis of these and other data, we suggest that the patient's simultanagnosia is attributable to an impairment in the process by which activated structural descriptions are linked to information coding the location of the object. PMID- 1884166 TI - Early onset cerebellar ataxia with retained tendon reflexes. Clinical, electrophysiological and MRI observations in comparison with Friedreich's ataxia. AB - Fourteen patients with the clinical diagnosis of early onset cerebellar ataxia with retained tendon reflexes (EOCA) were examined and compared with 11 patients with Friedreich's ataxia (FA). The mean age of onset in EOCA was 15.9 +/- 6.0 yrs (FA: 14.0 +/- 5.7 yrs). Annual progression rate and the percentage of patients who were wheelchair-bound was lower in EOCA as compared with FA, although the difference did not reach statistical significance. The latency until becoming wheelchair-bound, however, was significantly longer in EOCA than in FA. The segregation ratio in EOCA was significantly lower than 0.25. Clinically, EOCA and FA patients presented with a progressive cerebellar syndrome. Associated symptoms, such as muscle wasting, sensory disturbances, foot deformity, scoliosis and electrocardiographic abnormalities were encountered less frequently in EOCA than in FA patients. The electrophysiological findings in EOCA were variable and pointed to axonal degeneration in peripheral nerves and central pathways. Posturographic measurements revealed a higher incidence of anteroposterior sway direction in EOCA as compared with FA, suggesting a cerebellar type of ataxia in EOCA. Eleven out of the 14 EOCA patients had cerebellar atrophy in MRI. The characteristic MRI finding in FA was upper cervical cord shrinkage and only minor atrophy of the cerebellum. The demonstration of cerebellar atrophy in the majority of EOCA patients supports the view that EOCA is distinct from FA. It is uncertain, however, whether EOCA is a homogenous disease entity or a group of phenotypically similar syndromes. PMID- 1884167 TI - Mechanisms of visual spatial neglect. Absence of directional hypokinesia in spatial exploration. AB - This study examines whether visuospatial neglect derives from failure in directing hand movements to the left (directional hypokinesia), or from loss of mental representation of the left side of space. Forty right brain-lesioned patients, 28 of whom revealed mild, moderate, or severe neglect in clock drawing and cancellation tasks, were asked to search for concealed targets on a stimulus display board, by either (1) moving a covering panel with a small window until the target appeared, or (2) moving the stimulus display board beneath a stationary covering panel until the target became visible through the window. In the second procedure, the direction of physical space exploration and hand movement is reversed, so that in order to bring a target from the right side of the stimulus into view (under the window) the entire display board had to be moved to the left. This pair of procedures was supplemented by an analogous pair of visual tasks in which the entire display board was visible during the search. As expected, response times were generally longer for targets located on the left side of the display board; however, the direction of required hand movement (left vs right) did not have a significant effect on response times, irrespective of the degree of clinically assessed neglect. PMID- 1884168 TI - Cerebral potentials evoked by painful, laser stimuli in patients with syringomyelia. AB - Brief cutaneous heat stimuli generated by a CO2 laser were used to elicit late somatosensory evoked cerebral potentials (SEPc) in 10 patients with syringomyelia. For comparison, early and late cerebral potentials in response to electrical nerve stimuli (SEPn) were recorded in the same session. In 8 patients with localized impairment of pain and temperature sensitivity we found complete absence of SEPc after stimulation of the affected area; in another patient with similar sensory deficits, the SEPc was grossly attenuated and delayed. In 1 patient with intact pain sensitivity but absent temperature sensitivity, a well defined SEPc could be recorded. Both early cortical SEPn and late SEPn in response to conventional nerve stimuli were normal in all patients and thus did not differentiate control and affected areas. These data indicate that alteration of SEPc correlates with altered pain sensitivity in patients with a circumscribed spinal lesion. SEPc may thus be used as a neurophysiological test in the assessment of hypalgesic dermatomes. PMID- 1884170 TI - Impaired phonological reading in primary degenerative dementia. AB - This case study reports the profile of preserved and impaired capacities in a left-handed patient suffering from primary degenerative dementia of unknown aetiology. She was remarkable because her relatively preserved object naming and semantic categorization abilities contrasted with severe deficits in speech fluency, oral reading, inability to execute spoken and written commands, and severely impaired auditory-verbal short-term memory. Her reading disorder could be characterized as a disturbance of assembled phonology. She had great difficulty reading pronounceable nonwords, but she could correctly read irregular words. She showed effects of word imageability or concreteness (more than word frequency). She also showed effects of part-of-speech, where nouns and adjectives were read more easily than inflected verbs. She had difficulty reading function words. The syntactic category effects could be proven (by hierarchical log-linear analysis) not to be an artefact of imageability differences between verbs, adjectives and nouns. In reading aloud she made visual and morphological errors, but no semantic errors. This interesting pattern of preserved semantic information and disrupted phonological processing is unusual in dementia and contrasts with the severe dysnomia of patients with surface dyslexia who are able to read by the indirect, assembly-of-phonology route and show better reading of nonwords than irregular words. Her reading by a direct visual-semantic route appeared to be associated with relatively intact object naming, concrete word reading, and irregular word reading. This selective impairment of phonological reading in the context of partly preserved semantic abilities was interpreted as confirmation of the dissociability of language functions in primary degenerative dementia. PMID- 1884169 TI - A history of boron neutron capture therapy of brain tumours. Postulation of a brain radiation dose tolerance limit. AB - Boron neutron capture therapy (BNCT) is a form of radiation therapy mediated by the short-range (less than 10 microns) energetic alpha (4He) and lithium-7 (7Li) ionizing particles that result from the prompt disintegration by slow neutrons of the stable (nonradioactive) nucleus boron-10 (10B). Recent advances in radiobiological and toxicological evaluation of tumour-affinitive boron containing drugs and in optimization of the energies of neutrons in the incident beam have spurred interest in BNCT. This article presents a history of BNCT that emphasizes studies in the USA. A new dosimetric analysis of the 1959-1961 clinical trials of BNCT at Brookhaven National Laboratory is also presented. This analysis yields an acute radiation dose tolerance limit estimate of approximately 10 Gy-Eq to the capillary endothelium of human basal ganglia from BNCT. (Gy-Eq: Gray-equivalent, or relative biological effectiveness of a radiation component multiplied by the physical dose of the component (Gy), summed over the component kinds of radiation.) PMID- 1884171 TI - Visual recognition memory. Neurophysiological evidence for the role of temporal white matter in man. AB - A novel event-related potential (ERP) elicited by a visuospatial recognition memory task was recorded in 20 patients with temporal lobe epilepsy using depth electrodes sited in the temporal lobes. The ERPs comprised two components, an N400 and a P600, and were similar in morphology to the previously reported ERP to verbal recognition memory tasks. The two ERP components in both verbal and visuospatial tasks were dependent on stimulus type and our data suggest that they do not simply represent delayed P300 ERP responses. In 17/20 patients robust, reliable bilaterally present ERPs were elicited by both verbal and visuospatial memory tasks. N400 amplitude was larger in response to novel stimuli, whereas P600 amplitude was larger to repeated stimuli. P600 amplitude was larger in the right temporal lobe to both visuospatial and verbal stimulus material. N400 and P600 latencies did not vary with task, stimulus type or side of recording. In 3/20 patients, no ERPs were elicited by either memory task. In all 3 cases, unilateral temporal white matter abnormalities were demonstrated by magnetic resonance imaging. Behavioural measures, expressed in the form of standardized accuracy scores, did not differ from those of a normal control group, and hence are unlikely to account for the abnormalities in ERPs. These results are discussed with reference to the primate visual recognition memory pathway and suggest that ERPs to recognition memory tasks are generated by an interaction between the two homologous inferotemporal recognition memory pathways. PMID- 1884172 TI - Motor function of the monkey globus pallidus. 1. Neuronal discharge and parameters of movement. AB - In order to examine the role of the basal ganglia (BG) in the regulation of basic movement parameters, we recorded extracellularly from pallidal neurons in conscious monkeys during the performance of a sequential wrist movement task which was composed of a series of holds and ballistic jumps. The movement sequence was predictable and had to be performed within specified time restraints. We recorded the activity of 297 neurons whose discharges were related to the movement task. We included only neurons whose discharges were related to movements at or about the wrist joint by prior examination outside the behavioural paradigm. Each neuron discharged preferentially to one direction of movement at or about the wrist joint. No consistent correlation was found between neuronal discharge and initial joint position, static load application, amplitude of movement or velocity of movement. The mean onset of neuronal discharge was 2 ms after the onset of EMG activity. The findings implied little contribution from the pallidal neurons in the execution of the current movement or to the movement's parameters. The implications are that the basal ganglia are likely to be concerned with other aspects of movement control. PMID- 1884173 TI - Motor function of the monkey globus pallidus. 2. Cognitive aspects of movement and phasic neuronal activity. AB - In order to study the role of the basal ganglia (BG) in cognitive aspects of movement, we recorded extracellularly from pallidal neurons in conscious monkeys while they performed a sequential wrist movement task consisting of a series of holds and ballistic jumps. The movement sequence had to be performed within specified time restraints and was predictable. We recorded the activity of 297 neurons whose discharges were related to the movement task. The movement-related response was found to be influenced by the contextual setting and by the degree of difficulty of the task in a subgroup of 82 neurons with a clear response to the first ballistic movement. Predictable and easy movements were usually represented by more prominent movement-related responses in 46% of these neurons; 35% of neurons from a different subset of 105 neurons also demonstrated a second phasic response just before the end of the final hold period of the task. This response was also found to be influenced by the predictability of the final hold period, both in its time duration and also by the direction of the following ballistic movement in double jump tasks. These findings were in keeping with a cognitive role for the BG in movement performance. In particular we suggest that the phasic neuronal activity was an internal cue generated by the BG for predictable movements of a subconscious nature which signals the end of a component of movement in a movement sequence. This cue is appropriately timed to terminate sustained neuronal activity in the SMA and to allow the next movement in the sequence to be executed. PMID- 1884174 TI - Quadrantic visual field defects. A hallmark of lesions in extrastriate (V2/V3) cortex. AB - We report 2 patients with homonymous quadrantic visual field defects. The first patient experienced scintillations in the left lower quadrant, leading to the discovery of an astrocytoma in the cuneus of the right occipital lobe. Postoperatively she had a left lower quadrantanopia that precisely respected the horizontal meridian. The second patient presented with a left lower quadrantanopia, sparing the central 10 degrees of vision that also respected the horizontal meridian. An astrocytoma was resected from the right upper peristriate cortex. We must explain how a lesion in extrastriate cortex produced a homonymous field defect with a sharp horizontal edge in these 2 patients. Areas V2 and V3 are each divided along the horizontal meridian into separate halves flanking striate cortex. Consequently, the upper and lower quadrants in extrastriate cortex are physically isolated on opposite sides of striate cortex. We propose that a lesion involving V2/V3 may be sufficient to create a visual field defect. Although the lesion may have irregular margins, if it crosses the representation of the horizontal meridian in extrastriate cortex, it will produce a quadrantic visual field defect with a sharp horizontal border because of the split layout of the upper and lower quadrants in V2/V3. PMID- 1884175 TI - The aphasic isolate. A clinical-CT scan study of a particularly severe subgroup of global aphasics. AB - This paper outlines the clinical and CT scan features of a subtype of global aphasia, characterized by an extreme loss of communicative abilities, verbal as well as nonverbal. Three to four weeks after a left hemisphere stroke, 17 patients were completely unable to communicate with people addressing them. Though there were differences in their willingness to interact with the environment, they were characterized by complete loss of speech output and by inaccessibility to any kind of message, whether given verbally or through gestures. Patients who survived were reassessed 6 and 12 mos later and half of them were still found in a state of complete communicative isolation. The remainder had somewhat improved, but remained globally aphasic. The attempt to find a CT scan basis for this picture was disappointing. Only 35% of patients had a lesional pattern in agreement with the traditional view that ascribes global aphasia to the involvement of Broca's and Wernicke's areas. The location of lesion in the other cases spanned from anterior cortical damage, to posterior cortical damage, to deep nuclei damage and none of the lesions that have been proposed to account for subcortical global aphasia was consistently observed. PMID- 1884176 TI - Control of the transition from sensory detection to sensory awareness in man by the duration of a thalamic stimulus. The cerebral 'time-on' factor. AB - A 'time-on' theory to explain the cerebral distinction between conscious and unconscious mental functions proposes that a substantial minimum duration ('time on') of appropriate neuronal activations up to about 0.5 s is required to elicit conscious sensory experience, but that durations distinctly below that minimum can mediate sensory detection without awareness. A direct experimental test of this proposal is reported here. Stimuli (72 pulses/s) above and below such minimum train durations (0-750 ms) were delivered to the ventrobasal thalamus via electrodes chronically implanted for the therapeutic control of intractable pain. Detection was measured by the subject's forced choice as to stimulus delivery in one of two intervals, regardless of any presence or absence of sensory awareness. Subjects also indicated their awareness level of any stimulus-induced sensation in each and every trial. The results show (1) that detection (correct greater than 50%) occurred even with stimulus durations too brief to elicit awareness, and (2) that to move from mere detection to even an uncertain and often questionable sensory awareness required a significantly larger additional duration of pulses. Thus simply increasing duration ('time-on') of the same repetitive inputs to cerebral cortex can convert an unconscious cognitive mental function (detection without awareness) to a conscious one (detection with awareness). PMID- 1884177 TI - An analysis of lymphocyte 3H-N-methyl-scopolamine binding in neurological patients. Evidence of altered binding in Alzheimer's disease. AB - Muscarinic cholinergic receptors were analysed in lymphocyte membranes from 35 patients with early (n = 20) and late onset (n = 15) Alzheimer's disease (AD), 86 patients with other neurological disorders and 60 normal controls by the specific binding of 3H-N-methyl-scopolamine (3H-NMS). The number of binding sites of 3H NMS (Bmax) was significantly decreased both in early and late onset AD groups as compared with age-matched controls, by 54% and 40%, respectively, whereas the apparent binding affinity (Kd) was the same in all disease and control groups. In addition, the average Bmax in early AD was significantly lower than in late AD. The density of the binding of 3H-NMS was also significantly lower in a subgroup of old subjects with Down's syndrome (DS), whereas no changes were found in younger individuals with DS or in patients with Parkinson's disease, whether they were demented or not, multi-infarct dementia, myasthenia gravis or epilepsy. In the AD group, the difference in binding sites was unrelated either to the severity of dementia or disease duration. Treatment of the patients with cholinergic agents did not alter the binding values in any of the examined group. We conclude that the alteration of lymphocyte muscarinic receptors is highly associated with AD, but whether this reflects the central cholinergic deficit in these patients is uncertain. PMID- 1884178 TI - Preferential generation of recurrent responses by groups of motor neurons in man. Conventional and single unit F wave studies. AB - Conventionally recorded surface F waves over the abductor digiti minimi muscle sampled a wide range of conduction velocities (CVs). Single motor unit (MU) F responses to threshold stimulation of the ulnar nerve were recorded with bipolar needle electrodes (BNE); the mean latencies of their fastest associated surface single unit M and F potentials were similar to those of the compound muscle action potential and fastest F wave, indicating that the fastest F wave indexes adequately the fastest motor fibre of the ulnar nerve. The mean surface unit F amplitude of MUs recorded by a BNE was similar to that of voluntary MUs recorded with a spike-triggered averaging technique; an estimated mean of 2-3 MUs per F wave was found by two methods. The frequency distribution of estimated F wave CVs was shifted towards faster values than expected from available studies of the distribution of CVs in single peripheral nerves; it was also higher than predicted from the expected relation between this distribution and the number of MUs per F wave, if an equal chance of activation and recording is assumed for each MU. There was a significant positive correlation between the frequency of F responses and their CV in 81 single MUs recorded by a BNE and tested with 200 threshold stimuli. These findings are consistent with preferential generation of recurrent responses by larger MUs; it may relate to a lesser chance of antidromic discharge in the smaller motor neurons and to a greater chance of collision of orthodromic (reflex) and antidromic impulses in their axons. The higher than expected percentage of all F waves that were repeater shapes or waves, and the presence of several distinct peaks in the distribution of intervals between repeaters of the same shape, suggest special, and heterogeneous, functional and anatomical arrangements in the groups of motor neurons generating them. Repeaters had greater amplitude and area, but similar latency and duration, than F wave shapes that did not repeat, suggesting that the former have a larger number of component MUs. PMID- 1884179 TI - Distribution of cortical neural networks involved in word comprehension and word retrieval. AB - Six normal volunteers were studied with positron emission tomography to identify the cortical neural networks that participate in the processing of single words. Activity-related changes in regional cerebral blood flow were measured consecutively on 6 occasions in each subject, 2 while the subject was at rest and 4 while single word language tasks were being performed. The data from each subject were standardized for brain shape and size, reconstructed parallel to the intercommissural line, normalized for global flow differences, and then averaged for each activation condition across the 6 subjects. Significant areas of change in rCBF (P less than 0.05, with appropriate Bonferroni corrections) between task and rest conditions were displayed with reference to the coordinates of a standard neuroanatomical atlas. We have demonstrated that categorical judgements on heard pairs of real words activate neural networks along both superior temporal gyri, but with an anatomical distribution no different from that seen when the subjects listened to nonwords: the tasks would appear to be very different in cognitive demands but not in terms of the distribution of activation. However, during a verb generation task that involved thinking of verbs appropriate to heard nouns presented at a slow rate, the only temporal region activated was the left posterior superior temporal association cortex (Wernicke's area). Further analysis showed that whereas activation in other superior temporal regions, both left and right, correlated with rates of word presentation during the 4 tasks, there was no such correlation in Wernicke's area; evidence that this site is responsible for more than early acoustic processing. During verb generation there was also activation of left premotor and prefrontal cortex (including Broca's area and the supplementary motor area). The supplementary motor area is thought to be involved in the motor planning of speech. The subjects did not vocalize during the task, and therefore it would appear that the act of retrieving words from semantic memory activates networks concerned with the production of speech sounds. We conclude that single word comprehension and retrieval activate very different distributed regions of cerebral cortex, with Wernicke's area the only region engaged by both processes and with participation during silent word generation of networks involved in vocalization. PMID- 1884180 TI - Warm and cold specific somatosensory systems. Psychophysical thresholds, reaction times and peripheral conduction velocities. AB - Perception thresholds for warm and cold sensation were measured by two methods, the method of levels and the method of limits, at various rates of temperature change. The following findings were obtained. (1) The threshold value is critically dependent upon the method through which it is obtained, being higher for the method that includes reaction time in the measurement. (2) When using a method that includes participation of reaction time, threshold increases with increasing rate of temperature change. (3) The artefactual threshold elevation recorded through the method of limits corresponds precisely to the reaction time. (4) Conduction velocities for the primary afferents mediating the sensations of warm and cold, calculated on the basis of reaction time and conduction distance are in keeping with the mediation of warm sensation by unmyelinated primary afferents and of cold sensation by small myelinated afferents. (5) Measurement of threshold by the method of levels and direct measurement of reaction time enables calculation of conduction velocity for the specific sensory submodality tested from a single stimulation site. PMID- 1884182 TI - Hereditary motor and sensory neuropathy of neuronal type with onset in early childhood. AB - Eighteen cases of a chronic progressive motor and sensory neuropathy of neuronal type with early onset are described. Based on the presented data and literature reports a condition is distinguished, which is in clinical, genetic and morphological aspects different from autosomal dominant HMSN type II. The condition corresponds to that described by Ouvrier et al. (1981). It shows a congenital or early childhood onset and causes a severe disability usually with wheelchair dependency already in puberty or later in adult life. The condition is probably transmitted by an autosomal recessive gene. Morphological features of biopsied nerves are an extensive loss of large diameter fibres with a shift to smaller diameters in the histogram. Regenerative features are almost absent in contrast to the distinct cluster formation in autosomal dominant HMSN type II. A maturation disturbance of peripheral motor and sensory neurons with a concomitant or secondary process of chronic neuronal degeneration is suggested. One dominantly inherited case in our group with an infantile onset exhibits clinical and morphological features consistent with an autosomal dominant HMSN type II. PMID- 1884181 TI - The pathophysiology of chronic relapsing experimental allergic encephalomyelitis in the Lewis rat. AB - Electrophysiological studies were performed in Lewis rats with chronic relapsing experimental allergic encephalomyelitis (EAE) induced by inoculation with guinea pig spinal cord and adjuvants and treatment with low dose cyclosporin A. During clinical episodes there was conduction failure in the central nervous system (CNS), namely the spinal cord dorsal columns, and in the afferent fibres in the peripheral nervous system (PNS). The following observations indicated that the conduction failure was mainly due to demyelination-induced conduction block: (1) rate-dependent conduction block in the CNS and PNS; (2) temporal dispersion due to slowing of PNS conduction; (3) restoration of PNS conduction by cooling; (4) restoration of CNS conduction by ouabain; (5) previously demonstrated histological evidence of primary demyelination in the dorsal columns, dorsal root ganglia and dorsal roots; and (6) the temporal association of restoration of conduction with remyelination. However, it is likely that CNS and PNS axonal degeneration, which occurs in this disease, also contributed to the conduction failure. In clinical remissions there was restoration of conduction in the CNS and PNS which can be explained by ensheathment/remyelination by oligodendrocytes and Schwann cells, respectively. In most rats during clinical episodes the cerebral somatosensory evoked potential was reduced in amplitude and prolonged in latency, which can be accounted for by demyelination and axonal degeneration in the CNS and PNS components of the afferent pathway. In 2 rats with episodes of EAE, however, this potential was markedly increased in amplitude, which might have been due to demyelination-induced conduction block of descending pathways that normally inhibit synaptic transmission in the afferent pathway. In well established remission there was residual conduction failure in the CNS and PNS which can be mainly accounted for by axonal degeneration. PMID- 1884183 TI - Pain-related somatosensory evoked potentials in syringomyelia. AB - Pain-related somatosensory evoked potentials following CO2 laser stimulation (pain SEPs) and conventional electrically-stimulated SEPs (electric SEPs) were examined in 8 patients with syringomyelia who showed various forms of dissociated sensory loss. Unlike clinical examination using a pin or needle, pain SEP is considered to be an objective and quantitative test to investigate functions of peripheral and central sensory pathways responsible for pain-temperature sensation (A delta fibres and the spinothalamic tract). Pain SEPs were abnormal in all patients. The results were generally compatible with the degree of a clinical impairment of pain-temperature sensation. Subclinical abnormality was detected in 3 patients. Electric median nerve SEPs using the scalp reference (Fz) were normal in 6 out of 8 patients. However, anterior and posterior cervical responses using a noncephalic reference were absent or small in 7 patients. Electric SEPs following tibial nerve stimulation were normal in 7 patients. These findings suggest that the function of the ascending fibres through the dorsal columns is intact in most patients, whereas the dorsal horn, where a fixed cervical potential is generated, is impaired. Pain SEPs combined with electric SEPs therefore appear to be extremely useful for investigating physiological function in the sensory pathways in patients who show 'dissociated sensory loss' such as in syringomyelia. PMID- 1884184 TI - New observations on the normal auditory startle reflex in man. AB - The latency and pattern of muscle recruitment in the startle response elicited by unexpected auditory stimulation was determined in 12 healthy subjects. Reflex EMG activity was recorded first in orbicularis oculi. This was of similar latency to the normal auditory blink reflex and, unlike the generalized startle response, persisted despite the frequent presentation of the test stimulus. It is argued that this early latency activity in orbicularis oculi represents a normal auditory blink reflex and is not part of the generalized auditory startle reflex. With the exception of this early latency activity in orbicularis oculi, the relative latencies of both cranial and distal muscles in the auditory startle response increased with the distance of their respective segmental innervations from the caudal brainstem. Thus the earliest EMG activity was recorded in sternocleidomastoid. The recruitment of caudal muscles was relatively slow and the latencies of the intrinsic hand muscles were disproportionately long. The pattern of recruitment of cranial muscles suggests a brainstem origin for the normal startle response. Studies on the auditory startle reflex in animals are reviewed in the light of this finding. PMID- 1884185 TI - The hyperekplexias and their relationship to the normal startle reflex. AB - The startle response to unexpected auditory and somaesthetic stimulation was studied in 8 patients with hereditary or symptomatic hyperekplexia. It was abnormal in its resistance to habituation and in its exaggerated motor response. Both noise and taps to the face and head elicited a normal early blink response, separate from the subsequent true startle reflex. The earliest reflex EMG activity recorded after the blink was in sternocleidomastoid. EMG activity in masseter, and trunk and limb muscles followed later. This pattern of muscle recruitment suggests a brainstem origin for the abnormal startle responses. In addition, the abnormal startle responses exhibited disproportionately long latencies to the intrinsic hand and foot muscles and relatively slow recruitment of caudal muscles. The pattern of muscle recruitment was similar between patients, irrespective of the absolute latency of the response, and regardless of whether stimulation was auditory or somaesthetic. This suggests that auditory and somaesthetic afferents converge on a common brainstem efferent system, and that this system forms the final common pathway for abnormal startle responses of differing latency. The characteristics of this efferent system differ from those previously described in brainstem reticular reflex myoclonus, but are similar to those described in the normal auditory startle reflex in man. This suggests that the abnormal startle response in hyperekplexia, and the normal startle reflex represent pathological and physiological activity in the same brainstem efferent system. PMID- 1884186 TI - Vulnerability of nerve fibres to ischaemia. A quantitative light and electron microscope study. AB - In order to learn more about the vulnerability of nerve fibres to ischemia, a quantitative study of nerve fibre abnormalities was performed on biopsy specimens of the superficial branch of the peroneal nerve from 26 patients with vasculitic neuropathy: 20 had necrotizing arteritis, 5 a lymphocytic, and 1 a leucocytoclastic vasculitis on nerve and/or muscle biopsy. The density of myelinated fibres ranged from 25 to 7880 per mm2 (n = 8470 +/- 706 (SD]. There was a marked inequality in the density of nerve fibres between the fascicles of individual nerves with a mean coefficient of variation of 41 +/- 37 (SD) % versus 7.4 +/- 3.0% in controls. Loss of myelinated fibres, which was greater for fibres larger than 7 microns in diameter, was more severe than that for unmyelinated axons. Regeneration, which was assessed by the number of clustered axons, decreased when the density of myelinated fibres decreased, suggesting that severe nerve ischaemia precludes axonal regeneration. Wallerian degeneration affected on average 58% (range 5-100%) and segmental demyelination, mainly of the secondary type, on average 1.94% (range 1-10%) of teased fibres. It was concluded that (1) myelinated fibres are more vulnerable to ischaemia than unmyelinated axons; (2) large myelinated fibres are affected before the smaller ones; (3) segmental demyelination is uncommon in this context; (4) severe nerve ischaemia precludes axonal regeneration. PMID- 1884187 TI - Through a looking glass. A new technique to demonstrate directional hypokinesia in unilateral neglect. AB - A line cancellation task was performed by right brain-damaged patients with neglect in two response conditions. The task was presented either in normal view or through a 90 degree angle mirror with direct view prevented. The latter decouples the direction of visual attention and of arm movement. In the mirror condition, 4 of 18 patients cancelled lines only in right hemispace which means that they directed their visual attention to the left but failed to execute movements towards contralateral hemispace--what has been termed directional hypokinesia. In contrast, 10 patients cancelled lines only in left hemispace in the mirror condition, which accords better with attention-representation deficit hypotheses. Our results support a division of the neglect syndrome according to whether perceptual or premotor deficits are predominant. PMID- 1884188 TI - Phonolexical agraphia. Superimposition of acquired lexical agraphia on developmental phonological dysgraphia. AB - Study of neuropsychological sequelae of a focal acquired brain lesion may bring out and help delineate the features of a compensated developmental language disorder and its anatomical substrate. A left-handed man with a history of phonological developmental dyslexia and dysgraphia learned in early adulthood to read and write using a lexical system. Following a small posterior right parietal infarct when aged 56 yrs he developed a severe agraphia displaying features of phonological dysgraphia with impaired segmentation and features of lexical agraphia. Writing was severely impaired for all classes of word and nonword stimuli but his errors did not resemble those attributable to a deficit in the system responsible for the short-term storage of the graphemic representation of a word (graphemic output buffer). These observations imply that an acquired lexical agraphia has been superimposed on his developmental phonological dysgraphia, resulting in a combined or 'phonolexical' agraphia. PMID- 1884189 TI - Trunk orientation as the determining factor of the 'contralateral' deficit in the neglect syndrome and as the physical anchor of the internal representation of body orientation in space. AB - The present study examines which egocentric coordinate system determines the border between the disturbed 'contralateral' and the normal 'ipsilateral' side in patients with hemineglect. Based on the observation of significantly longer reaction times for saccades towards stimuli presented in the left visual field (LVF) in right brain-damaged patients with hemineglect, stimuli were presented randomly to the LVF or RVF and the corresponding saccadic reaction times (SRTs) were compared. Beginning with the standard body position generally used for the investigation of neglect patients, where the midlines of head, trunk and visual field are parallel and oriented straight towards the middle of the projection screen, the spatial relation between orientation of head and trunk midlines and location of the target stimuli was systematically varied while holding the retinal projection of the stimuli constant. The deficit in SRTs towards the LVF in 4 right brain-damaged patients with left-sided hemineglect could be compensated for by turning the patients' trunk to the left, such that both LVF and RVF-stimuli were projected to the right, ipsilateral side of trunk space. The results suggest that the spatial orientation of the trunk midline divides our normal perception of space into an egocentric 'left' and an egocentric 'right' sector and seems to be the decisive factor for determining the neglected 'contralateral' part of space in patients with brain-damage. They indicate that the trunk midline constitutes the physical anchor for calculation of the internal egocentric coordinate frame for representing body position with respect to external objects. The hypothesis of Ventre et al. (1984) that deficient reactions to contralaterally located stimuli in neglect patients could be the result of a displacement of these egocentric coordinates towards the non-neglected, ipsilateral side is discussed. PMID- 1884190 TI - Hemispheric specialization for semantic and syntactic components of language in simultaneous interpreters. AB - Hemispheric specializations for semantic and syntactic components in Italian (L1) and English (L2) were studied with a dichotic listening test, simulating simultaneous interpretation tasks in 24 right-handed female interpretation students at the Scuola Superiore di Lingue Moderne per Interpreti e Traduttori (SSLM) of the University of Trieste and in 12 right-handed female professional interpreters at the European Communities (EEC). The test involved the recognition of correct translations, translations with semantic errors, and translations with syntactic errors from L1 to L2 and vice versa. As an overall result, both students and interpreters gave significantly more correct answers when sentences in L2 as the target language were sent to the left ear. Students recognized significantly more sentences containing syntactic errors than did professional interpreters, while professional interpreters recognized significantly more sentences with semantic errors than did interpreting students. In regard to hemispheric specialization in interpreting students, no significant asymmetries were revealed in the recognition of semantic and syntactic errors. Professional interpreters showed a significant right-ear superiority in recognizing semantic errors in L1 and a significant left-ear superiority in recognizing semantic errors in L2. In the recognition of syntactic errors, professional interpreters showed significant left-ear superiority for L1 and significant right-ear superiority for L2. The prolonged practice in simultaneous interpreting strategies in EEC professional interpreters may account for some of their peculiar hemispheric specializations for languages revealed by this study. PMID- 1884191 TI - MRI findings in boys with specific language impairment. AB - Magnetic resonance imaging scans of specifically language-impaired (SLI) boys were examined to determine whether atypical cerebral findings could be documented in children whose primary deficits were in language skills. Clinical examination of the scans failed to reveal any visually obvious lesions or abnormalities. In contrast, measurement of the scans revealed atypical perisylvian asymmetries in most of these subjects. The distribution of perisylvian asymmetries in SLI subjects was significantly different from the distribution in controls (p less than .01). Measurement of other brain regions revealed that extraperisylvian areas were occasionally deviant in individual SLI subjects; but no one region was consistently deviant across the SLI group. Thus, only atypical perisylvian asymmetries were linked to the language disorder. These neuroanatomical findings suggest that a prenatal alteration of brain development underlies specific language impairment. PMID- 1884192 TI - MRI findings in the parents and siblings of specifically language-impaired boys. AB - Four families that include a specifically language-impaired (SLI) boy were studied to test the hypothesis that developmental language disorders are biologically transmittable. A majority of the parents of the SLI boys had experienced communication difficulty (i.e., difficulty with speech, language, or academic skills) as children. Evidence of communication difficulty was paired on an individual basis with neuroanatomical data obtained through quantitative analysis of magnetic resonance imaging scans. Atypical perisylvian asymmetries were documented in a majority of the parents and were frequently associated with a history of communication difficulty. Atypical perisylvian asymmetries and disordered language skills were also documented for siblings of SLI boys. These findings suggest that atypical perisylvian asymmetries reflect a transmittable, biological factor that places some families at risk for language impairment. PMID- 1884193 TI - Phenotypic profiles of language-impaired children based on genetic/family history. AB - Although etiological influences in developmental language impairment (dysphasia) are not well defined, a significant increase of family aggregation for the disorder has been reported. We report data from a large cohort of language impaired (LI) children participating in the San Diego longitudinal study in which we examined whether children with or without positive family histories show different phenotypic profiles. Due to the longitudinal design of the study, questions pertaining to change over time are also addressed. Second, a subgroup of the most impaired children were reevaluated to obtain additional information pertaining to family history and phenotypic outcome. Approximately 70% of the LI children met criteria for inclusion as family history positive, with fathers reporting a history of language or learning problems one and a half to two times as frequently as mothers. LI children with or without a positive family history were not significantly different on language skills or IQ. However, subjects having a positive family history for developmental language/learning problems were significantly lower in socioeconomic status and were rated by parents and teachers as having more attention-related behavior problems than their family history negative counterparts. Similarly, family history positive LI children performed more poorly on standardized academic tests as well as on tests of auditory processing and attention. PMID- 1884194 TI - Predominant localization in glial cells of free L-arginine. Immunocytochemical evidence. AB - Nitric oxide has been recently identified as an endogenous activator of the soluble guanylate cyclase in the brain as well as in vascular endothelial cells and macrophages. In the present study, we determined the localization of free arginine in the brain because nitric oxide was formed from the terminal guanido group of L-arginine. Anti-arginine antiserum was raised in guinea pigs by repeated injection of L-arginine covalently conjugated to guinea pig serum albumin via glutaraldehyde. Specific anti-arginine antibody was purified from the antiserum by using an affinity gel coupled with L-arginine. Arginine-like immunoreactivity in the rat brain and spinal cord was found concentrated mainly in astrocytes including Bergmann glial cells in the cerebellum and processes of astrocytes around blood vessels. The present results suggest that glial cells, particularly astrocytes, are the main locus of L-arginine, a nitric oxide precursor, in the brain. PMID- 1884195 TI - Effect of protein kinase C modulation on outcome of experimental CNS ischemia. AB - Protein kinase C (PKC) is an important intracellular regulator, and its activity may play a central role in the modulation of neuronal ischemic damage. Staurosporine and the compound H-7 are potent in vitro inhibitors of PKC, and 1,2 oleoylacetylglycerol (OAG) is an effective activator. We administered these compounds through a spinal subarachnoid catheter and demonstrated in vivo alteration of spinal cord PKC activity. We then tested the effects of altering PKC activity in a well-established rabbit model of reversible spinal cord ischemia. Animals within each experimental group were subjected to a range of spinal cord ischemic durations by temporary occlusion of the infrarenal abdominal aorta. Compared to control, both staurosporine and H-7 significantly shortened the duration of ischemia that the animals could tolerate, without developing permanent paraplegia. OAG resulted in an insignificant lengthening of the ischemic duration that the animals could withstand. The worsening of ischemic outcome by PKC inhibitors suggests that the enzyme is important for maintaining neurologic function under ischemic conditions, possibly secondary to modulation of intracellular calcium levels. PMID- 1884196 TI - Multiple fluorescent ligands for dopamine receptors. II. Visualization in neural tissues. AB - Selective dopamine receptor ligands, (R,S)-5-(4'-aminophenyl)-8-chloro-2,3,4, 5 tetrahydro-3-methyl-[1H]-3-benzazepin-7-ol, the 4'-amino derivative of the high affinity D1 receptor antagonist SCH 23390, the high affinity D2 receptor antagonist N-(p-aminophenethyl)-spiperone or NAPS, and the D2 selective agonist, 2-(N-phenethyl-N-propyl)-amino-5-hydroxytetralin or PPHT were chemically coupled to the fluorescent compounds, Bodipy, Cascade blue, coumarin, fluorescein, rhodamine, or Texas red. The utility of the 6 fluorescent moieties linked to the 3 dopamine receptor binding ligands for anatomical study of regional and cellular distribution patterns of the two dopaminergic receptor subtypes has been assessed in frozen sections of the rat striatum and compared to our previous report using the rhodamine-labeled antagonists. The regional staining for the two dopaminergic receptor binding sites supports previous work using in vitro receptor autoradiographic analyses; the D1 receptor binding was more robust than that of D2 receptors in the caudate nucleus. The cellular element which most frequently expressed striatal D1 binding sites had a medium-diameter cell body. Medium-sized cells also exhibited fluorescence for the D2 binding site, as did a much larger diameter element; potentially the cholinergic interneuron of the caudate nucleus. The pharmacological specificity for each of the different D1 fluorescent antagonist ligands in the tissues was determined by competition with 100-fold excess of unlabeled SCH 23390 (non-specific binding), spiroperidol (binding selectivity), the stereoactive paired isomers of butaclamol, and the serotonin 5 HT2 receptor antagonist ketanserin. The same criteria were used to assess the different D2 fluorescent agonist and antagonist ligand derivatives. The anatomical efficacy of these novel ligands was determined using selective dichroic filters to stimulate the fluorescent moieties in the optimal excitation wavelength, and the amount of fluorescent dopamine receptor binding was photographically measured and contrasted for each of the newly synthesized fluoroprobes. Using the most pharmacologically specific and anatomically efficient of these novel fluoroprobes, we determined the localization pattern of the D1 and D2 dopamine receptor binding sites in tissues reported to exhibit both subtypes of the receptor. The cellular distribution of the dopamine receptor binding sites was determined concurrently using fluoroprobes in the forebrain, mesencephalon, pituitary, retina, and superior cervical ganglion of the rodent, and bovine adrenal medullary chromaffin cells were examined using the rhodamine labeled antagonists. PMID- 1884197 TI - Origin of contralateral reactive gliosis in surgically injured rat cerebral cortex. AB - While reactive gliosis is readily observed close to the site of cerebral injury, astrocyte reactivity can also occur in distant areas either ipsilateral or contralateral to the lesion site. The present experiments were designed to address the origin of contralateral gliosis in adult rats following a cortical stab wound injury. One-month-old rats were subjected to either left cortical stab wound alone, callosotomy alone, callosotomy plus left cortical stab wound, or no surgery; 7 days later, animals were sacrificed. Formalin-fixed, paraffin-embedded sections were obtained and immunostained for GFAP. While untreated controls showed no cortical gliosis, callosotomy alone induced mild bilateral cortical gliosis. Whether or not rats were subjected to a callosotomy, the left cortical stab wound produced identical results: severe ipsilateral cortical gliosis and moderate contralateral gliosis. In all lesion models, both the intensity of GFAP staining and the number of reactive astrocytes were most marked in cortical areas abutting the subarachnoid spaces and decreased gradually into the deeper cortical layers. Our results suggest that the origin of contralateral gliosis in cortical stab injury is more likely due to the release of soluble substance(s) which diffuse to distant areas, rather than the migration of astrocytes through the corpus callosum from the lesion site, or being subsequent to degeneration of neurons which fibers traverse the corpus callosum. PMID- 1884198 TI - Subsets of olfactory and vomeronasal sensory epithelial cells and axons revealed by monoclonal antibodies to carbohydrate antigens. AB - Cell surface glycoconjugates are believed to play an important role in cell-cell interactions during development of CNS pathways. In order to identify developmentally regulated glycoconjugates in the nervous system, monoclonal antibodies were raised and selected for reactivity with carbohydrate antigens. Three monoclonal antibodies were identified, each of which reacts with a defined carbohydrate epitope and reveals a unique pattern of immunoreactivity within the olfactory sensory epithelia, vomeronasal and olfactory nerves and their terminal regions in rats. Antibody CC1 reacts with a globoside-like glycolipid which contains a terminal N-acetylgalactosamine residue. CC1-immunoreactivity is present in just the vomeronasal organ, vomeronasal nerve and in the rostral half of the accessory olfactory bulb. Antibody CC2 reacts with a complex glycolipid which contains a branched chain oligosaccharide terminating with alpha-galactose and alpha-fucose. CC2-immunoreactivity is seen throughout the vomeronasal organ, in dorsomedial regions of the olfactory sensory epithelia, in the vomeronasal and olfactory nerves, the accessory olfactory bulb and dorsomedial glomeruli of the main olfactory bulb. Antibody 1B2 reacts with lacto-N-glycosyl ceramides. 1B2 immunoreactivity is highest at the luminal surfaces of receptor cells throughout the vomeronasal organ and in portions of the olfactory sensory epithelia. 1B2 is also expressed on the surface of a subset of receptor cell bodies, their dendrites and the proximal region of their axons in dorsomedial regions of the main olfactory epithelium. PMID- 1884199 TI - Sensorimotor performance and rotation correlate to lesion size in right but not left hemisphere brain infarcts in the spontaneously hypertensive rat. AB - In order to correlate behavioural deficits to lesion size and to reveal possible functional asymmetries in the rat brain, locomotor activity, rotation and sensorimotor integration to touch were studied in spontaneously hypertensive rats (SHR) subjected to right or left middle cerebral artery occlusion. Control and infarcted rats showed no difference in locomotor activity. Infarcted rats tended to rotate towards the side of the lesion. A large sensorimotor deficit was found contralateral to the infarcted hemisphere. The absolute values of the side-biases for the rotation and sensorimotor tests were of the same degree irrespective of lesion side. Whereas the left hemisphere lesion size did not correlate to the behavioural outcome, the size of the right hemisphere lesion was highly correlated to the total sensorimotor deficit. Furthermore, the sensorimotor deficit of specific body parts was found to correlate to the damage of certain brain regions in a rostrocaudal fashion, reminiscent of a somatotopical organization. The extent of ipsilateral rotation correlated to brain tissue loss at the level of the posterior caudate-putamen. The present results indicate an asymmetrical organization for brain functions involved in the performance of the rotation and sensorimotor tests. PMID- 1884200 TI - Intracellular pH and some membrane characteristics of cultured carotid body glomus cells. AB - Clusters of carotid body (glomus) cells cultured from a few days to 3 weeks, maintained their morphological characteristics during this period. The resting potential (Em) and input resistance (Ro) did not change for 2 weeks but both declined afterwards. The intracellular pH (pHi) of glomus cells, measured with glass microelectrodes filled with an H+ ion exchanger, was 6.34-6.96 at extracellular pH (pHo) of 7.32-7.53. Changes in pHo from normal to about 5.5 depolarized most cells but the fall in pHi was less marked than predicted by the Nernst equation. Conversely, shifting pHo to 8.5 hyperpolarized the cells with an increase in pHi which was more acid than predicted. EH (the calculated equilibrium potential for H+ (Nernst equation) was more positive than Em during acidity and more negative during normal or alkaline pHo. The kinetics of H+ ion distribution was assessed by brief exposures to NH4Cl. It is concluded that hydrogen ions are not passively distributed across the glomus cell membranes and that Em is dependent on H+ ions. PMID- 1884201 TI - The mouse gene retinal degeneration (rd) may reduce the number of neurons present in the adult hippocampal dentate gyrus. AB - C57BL/6J and C57BL/6J-rd le Gus-sh mice, congenics at the rd locus, were compared with respect to number of granule cells and presumed pyramidal basket cells in the hippocampal dentate gyrus. Number of both types of neurons were less in rd/rd mice than in +/-/+/- mice. The rd gene may be responsible. PMID- 1884202 TI - The projection of noradrenergic neurons in the A7 catecholamine cell group to the spinal cord in the rat demonstrated by anterograde tracing combined with immunocytochemistry. AB - Noradrenergic neurons located in the A5, A7 and locus coeruleus/subcoeruleus (LC/SC) catecholamine cell groups innervate all levels of the spinal cord. However, the specific spinal cord terminations of these neurons have not been clearly delineated. This study determined the spinal cord terminations of the A7 catecholamine cell group using the anterograde tracer Phaseolus vulgaris leucoagglutinin (PHA-L) in combination with dopamine-beta-hydroxylase (DBH) immunocytochemistry. In addition, the spinal cord projections of A7 neurons were examined by measuring the reduction in the density of DBH-immunoreactive axons in specific regions of the spinal cord after a unilateral electrolytic lesion of the A7 cell group. The results of these experiments indicate that noradrenergic neurons in the A7 cell group project primarily in the ipsilateral dorsolateral funiculus and terminate most heavily in the dorsal horn (laminae I-IV). PMID- 1884203 TI - The effects of chronic ethanol exposure on N-methyl-D-aspartate-stimulated overflow of [3H]catecholamines from rat brain. AB - The effects of acute and chronic ethanol administration on N-methyl-D-aspartate stimulated catecholamine overflow were examined. Three groups of male Sprague Dawley rats were used. The first group received a chronic liquid diet containing ethanol (37%) for 3 weeks. The second group was pair-fed a liquid diet with dextrin substituted for ethanol isocalorically. The third group received Purina rat lab chow and water ad libitum. N-methyl-D-aspartate-stimulated [3H]catecholamine overflow from brain tissue slices was determined. N-methyl-D aspartate (50-2000 microM) produced a concentration-dependent increase in [3H]norepinephrine overflow from cortical and hippocampal slices with no significant alteration of the response following chronic ethanol treatment. [3H]Dopamine overflow from striatal slices of the chronic ethanol group was significantly different at 1000 microM N-methyl-D-aspartate. The response of the chronic ethanol-treated group at the 1000 microM N-methyl-D-aspartate concentration was 30% and 40% lower than the pair-fed and ad libitum controls, respectively. Ethanol when added in vitro (30-200 mM) produced a concentration dependent inhibition of N-methyl-D-aspartate (150 microM) stimulated efflux in all brain regions, and chronic ethanol treatment did not alter the inhibitory response. These results indicate an apparant lack of adaptation in N-methyl-D aspartate-stimulated transmitter release following chronic ethanol treatment in this particular paradigm. PMID- 1884204 TI - Structural modeling of functional neural pathways mapped with 2-deoxyglucose: effects of acoustic startle habituation on the auditory system. AB - This paper describes the first application of structural modeling to neuroscience. Structural modeling (also known as path analysis) is a method to assess the relative impact of directional links in a system and how these interrelations may change under different conditions. The objective was to demonstrate how structural modeling can be used to determine the functional interrelationships between brain structures that form the auditory system. Using structural modeling, changes in auditory system 2-DG uptake were examined during long- and short-term habituation of the acoustic startle reflex. Models were based on the anatomical connections between central auditory system structures. Using functional 2-DG data, the correlations between these structures were calculated and numerical weights were computed for each anatomical link. The analysis revealed that the lemniscal path was dominant during short-term habituation, while during long-term habituation this influence was modified through extra-lemniscal pathways. The models are discussed in the context of previous findings to demonstrate how structural modeling can not only complement, but also extract more information from 2-DG mapping experiments. PMID- 1884205 TI - Septal unit activity during classical conditioning: a regional comparison. AB - Single unit activity was recorded from the lateral and medial septum of rats during aversive Pavlovian differential conditioning. One conditioned stimulus (CS+) was consistently paired with and another (CS-) was explicitly unpaired with a brief shock unconditioned stimulus (US). In the lateral septum single unit activity generally increased in the presence of a conditioned inhibitor of fear (CS-), while unit activity generally decreased in the presence of a conditioned excitor of fear (CS+). Responses in the medial septum were more heterogeneous. Many cells did not show plastic changes to the CSs, others showed responses to the conditioned stimuli opposite to that seen in the lateral septum. A small group of cells showed responses similar to that seen in the lateral septum. Finally, theta bursting cells were seen in the medial septum with some evidence of increased theta activity in the presence of a conditioned inhibitor of fear (CS-). The results were interpreted as consistent with the proposition that the lateral septum mediates the inhibition of aversive emotional states. The medial septum may have some involvement with the activation of fear or anxiety. PMID- 1884206 TI - Immunohistochemical localization of raf protein kinase in dendritic spines and spine apparatuses of the rat cerebral cortex. AB - The ultrastructural localization of raf protein (product of the raf protooncogene) in the neocortex, pyriform cortex and hippocampus of the rat has been investigated by means of pre-embedding immunohistochemistry. Specificity of the antiserum was tested with Western blotting. Besides the immunoreactivity of the dendrites, remarkably strong immunostaining of the dendritic spines and spine apparatuses was noted in each of the investigated areas. The postsynaptic densities were also stained. Since raf proteins are serine/threonine-specific protein kinases, our findings could be important steps toward the understanding of dendritic spine plasticity. PMID- 1884207 TI - Protein kinase C activity and intracellular distribution in surgically excised human epileptic neocortex. AB - Protein kinase C (PKC) activity assayed by phosphorylation of exogenous histone, was measured in neocortex obtained from 32 patients following surgery for focal epilepsy and from 6 non-epileptic patients. PKC activity was not significantly different in either the particulate or cytosolic fraction from epileptic foci (n = 17) versus samples from non-spiking regions (n = 22) or neocortex from non epileptic patients (n = 6). From 67% to 70% of total PKC activity was present in the cytosolic fraction. Phosphorylation of endogenous cytosolic substrate proteins was also not significantly different in epileptic foci. PMID- 1884208 TI - Strychnine antagonizes jaw-closer motoneuron IPSPs induced by reticular stimulation during active sleep. AB - In chronic, unanesthetized, normally respiring cats, stimulation of the nucleus reticularis pontis oralis induced inhibitory postsynaptic potentials (IPSPs) in masseter motoneurons during active sleep, but not during wakefulness or quiet sleep. Strychnine, when applied juxtacellularly by microiontophoresis to masseter motoneurons, specifically suppressed the active sleep-dependent IPSPs. In contrast, bicuculline did not suppress the active sleep-dependent IPSPs. These results indicate these IPSPs are mediated by the putative neurotransmitter glycine. PMID- 1884209 TI - Decline in cholesteryl ester hydrolase activity of rat brain with progress of experimental allergic encephalomyelitis followed by rebound during recovery. AB - Cholesteryl ester hydrolase and cholesteryl esters were measured in brain homogenates from rats in various stages of experimental allergic encephalomyelitis (EAE), a model for multiple sclerosis, and in age-matched controls. Cholesteryl esters were elevated approximately 280-507% in EAE rats with clinical indices of 1-3, corresponding to increasing severity of symptoms, but were not significantly different from controls upon disappearance of symptoms during the recovery period (stage = R2). Cholesteryl ester hydrolase declined progressively 12-34% during stages 1-3, rebounded to a level 16% greater than controls during the initial stage of recovery (R1) and remained significantly elevated by 6% over controls upon disappearance of symptoms (R2). A highly significant (P less than 0.001) correlation of reduction in cholesteryl ester hydrolase activity with clinical index was confirmed by linear regression analysis (R = 0.91). It is concluded that a decline in cholesteryl ester hydrolase activity is an early event in EAE which leads to accumulation of cholesteryl esters and may play a role in induction and progression of this demyelinating disorder. PMID- 1884210 TI - Presynaptic localization of omega-conotoxin-sensitive calcium channels at the frog neuromuscular junction. AB - By the use of anti-omega-CTx antibodies in indirect immunofluorescence we demonstrated the presence of omega-CTx binding sites in the presynaptic compartment of frog nerve-muscle preparations. The images we obtained indicate that omega-CTx-sensitive channels are clustered at discrete sites corresponding in distribution to active zones. PMID- 1884211 TI - Characterization of vanilloid receptors in the dorsal horn of pig spinal cord. AB - Specific [3H]resiniferatoxin binding is thought to represent the postulated vanilloid (capsaicin) receptor. We have previously characterized [3H]resiniferatoxin binding to membranes from rat and pig dorsal root ganglia, which contain the cell bodies of capsaicin-sensitive primary afferent neurons. We now demonstrate specific binding of [3H]resiniferatoxin to particulate preparations from pig dorsal horn, which contains the central nerve endings of the capsaicin-sensitive primary afferent neurons. The Kd was 0.27 +/- 0.03 nM; the Bmax was 370 +/- 40 fmol/mg protein. Vanilloids of the capsaicin class (capsaicin, piperine, zingerone) and resiniferatoxin class (tinyatoxin, 12 deoxyphorbol 13-phenylacetate 20-homovanillate) inhibited binding with affinities consistent with their relative in vivo potencies. Given the interest in vanilloids as potential non-narcotic analgesic agents, this binding assay affords an attractive approach for characterization of structure-activity relations at spinal vanilloid receptors. PMID- 1884212 TI - Parvalbumin-immunoreactive neurons in the cerebral cortex of the lizard Podarcis hispanica. AB - An antibody against the calcium binding protein parvalbumin selectively labels a set of neurons in the cerebral cortex of lizards. Golgi-like immunostained bipolar, multipolar and pyramid-like neurons appear mainly located in the inner plexiform layers. Parvalbumin-immunoreactive (PARV-IR) puncta are concentrated in the cell layer of the dorsal and dorsomedial cortices showing a basket-like distribution. The morphology and distribution of PARV-IR neurons and puncta overlap GABA-immunostaining in the cerebral cortex of lizards. Thus, it is likely that PARV-IR neurons are a subset of the cortical GABAergic neurons of lizards. PMID- 1884213 TI - Excitatory amino acids rise to toxic levels upon impact injury to the rat spinal cord. AB - The release of glutamate, aspartate, glutamine and asparagine upon impact injury to the rat spinal cord was characterized by sample collection from the site of injury by microdialysis. Injury caused dramatic and long-lasting increases in the concentrations of the excitatory amino acids. Determination of the relationship between unperturbed extracellular levels and the levels of amino acids in the collected fluids indicates that the concentrations of these amino acids were probably high enough to kill neurons for longer than one hour following impact injury to the spinal cord. Increases in the concentrations of the metabolically related non-neurotransmitters asparagine and glutamine were considerably smaller. The latter observations suggest that much of the increase in levels of the excitatory amino acids resulted from neuronal activity rather than from simple damage. PMID- 1884214 TI - A possible mechanism of action of the neurotoxic agent iminodipropionitrile (IDPN): a selective aggregation of the medium and heavy neurofilament polypeptides (NF-M and NF-H) AB - Juvenile male rats treated acutely with the neurotoxic agent, iminodipropionitrile showed no changes in the levels of total neurofilament subunit mRNA or protein for up to 28 days. However, the drug promoted aggregation of the neurofilaments, both spontaneously upon isolation and in an in vitro reassembly assay. This observation correlated with a basic pI shift of the heavy neurofilament subunit, due to a yet to be identified modification. Because of the crucial involvement of this neurofilament subunit in axonal integrity, it is likely that iminodipropionitrile produces a major portion of its neurotoxicity through this mechanism. PMID- 1884215 TI - Bursting properties of units in cat globus pallidus and entopeduncular nucleus: the effect of excitotoxic striatal lesions. AB - The bursting properties of units recorded in globus pallidus and entopeduncular nucleus were studied in awake cats sitting quietly before and after ipsilateral excitotoxic striatal lesions. A computerized statistical procedure was used to identify and evaluate bursts in the recorded spike trains. Bursts were assigned a quantitative statistical measure of burst 'strength' (or improbability) - the surprise value. Before the lesion, 34% of units in the globus pallidus and 60% of units in the entopeduncular nucleus exhibited bursts. Burst units had a significantly slower discharge rate and a significantly greater variability of discharge than non-burst units. The mean length of the interspike intervals immediately preceding the bursts was significantly longer than the overall median intervals in burst units. After the lesion, 21% of units in the globus pallidus and 11% of the units in the entopeduncular nucleus exhibited bursts. Burst units had significantly higher discharge rates and lower discharge variability after the lesion. In contrast, the lesion had no significant effect on the rate or variability of non-burst units. The differences between bursting and non-bursting units in discharge rate and variability disappeared after the lesion. In globus pallidus, the lesion resulted in a significant reduction in the mean number of bursts per unit, surprise value per burst, mean length of bursts, and number of spikes per burst, and a significant increase in the mean discharge rate of burst units. In entopeduncular nucleus, the small number of bursts recorded after the lesion precluded a useful statistical comparison of the effect of striatal lesions on the properties of the bursts. This study demonstrates that removing striatal projections to globus pallidus and entopeduncular nucleus decreases bursting in these nuclei, indicating that intact striatal projections are necessary for the normal production of bursts in these regions. PMID- 1884216 TI - The striatum and motor cortex in motor initiation and execution. AB - The participation of striatal and motor cortex neurons in motor initiation and execution was studied using single neuronal recording in 3 monkeys performing wrist flexion and extension stimulus-initiated reaction time tasks. Observations of 46 striatal neurons whose activity correlated with the tasks were compared to recordings of 59 task-related motor cortex neurons. Neurons were classified as best related to the appearance of the go signal, movement onset, agonist or antagonist electromyographic changes, or the movement reaching target. Timing of neuronal activity changes in both striatum and motor cortex suggested that go signal-related neurons represent input function while most movement onset-related neurons represent output function. In the striatum, those related to reaching target represent output function. Furthermore, go signal-related neurons usually change activity before movement onset-related neurons which change activity prior to target attainment-related neurons. These observations suggest a hierarchical organization within the striatum and motor cortex. Also the striatum participates in programming target acquisition as well as motor initiation. PMID- 1884217 TI - MK-801 attenuates the dopamine-releasing but not the behavioral effects of methamphetamine: an in vivo microdialysis study. AB - Neuroanatomical and pharmacological evidence suggests that important modulatory relationships exist between mesostriatal dopaminergic terminals and corticostriatal inputs. The present study used in vivo microdialysis in awake animals to examine the results of pharmacological manipulations of these systems on net striatal dopamine (DA) efflux and behavioral activation. A single methamphetamine (m-AMPH) treatment induced a prolonged (greater than 6 h) increase (6-fold peak response) in extracellular striatal DA and increased stereotypic behavior. When given alone, the non-competitive N-methyl-D-aspartate (NMDA) antagonist MK-801 did not have a significant effect on extracellular striatal DA, but significantly increased stereotypic behaviors. Pretreatment with MK-801 markedly attenuated the m-AMPH-induced striatal DA overflow. In contrast to its effects on striatal DA overflow, MK-801 potentiated the locomotor effects of m-AMPH without reducing stereotypy rating scores. These findings suggest that the synaptic relationships between mesostriatal DA and corticostriatal excitatory amino acid terminals in the striatum are an important component in its behavioral output. Moreover, NMDA receptors appear to be capable of modulating striatal DA overflow. PMID- 1884218 TI - Corticosterone regulation of type I and type II adrenal steroid receptors in brain, pituitary, and immune tissue. AB - Type I and Type II adrenal steroid receptor levels were compared in the brain, pituitary and immune system of adrenalectomized rats in the presence or absence of several replacement doses of corticosterone. Six days of adrenalectomy produced an up-regulation of Type II adrenal steroid receptors in the brain and spleen. The lowest replacement dose of corticosterone (equivalent to resting levels of this hormone) blocked this Type II receptor up-regulation, while higher replacement doses of corticosterone were associated with widespread Type I and Type II adrenal steroid receptor down-regulation. However, the dose of corticosterone required for receptor down-regulation varied between tissues. Specifically, hippocampal receptors were most sensitive to corticosterone, whereas pituitary receptors were the least sensitive. All tissues examined, except the pituitary, exhibited a down-regulation of Type II receptors with a high corticosterone replacement dose which approximated acute stress levels of this hormone. In summary, physiologically relevant concentrations of corticosterone were capable of down-regulating Type I and Type II adrenal steroid receptors in multiple brain areas and peripheral immune tissues, including peripheral blood mononuclear cells. In contrast, adrenal steroid receptor levels in the pituitary were relatively insensitive to regulation by corticosterone. PMID- 1884219 TI - Estrogen receptor binding in regions of the rat hypothalamus and preoptic area after inhibition of dopamine-beta-hydroxylase. AB - Previous studies have shown that administration of diethyldithiocarbamate (DDC), a dopamine-beta-hydroxylase inhibitor, results in a decreased concentration of estrogen receptors measured in the rodent hypothalamus and preoptic area. To determine if this modulation of receptor content is region-specific, in vitro estrogen binding assays were performed on cytosol and cell nuclear extracts of microdissected brain regions from female rats treated with DDC. For cytosol binding comparisons, ovariectomized (OVX) rats were treated with 550 mg DDC/kg b. wt. or the saline vehicle 12 h before sacrifice. For cell nuclear binding comparisons, OVX rats received a maximal dose of estradiol 12 h after DDC or saline treatment and 1 h before sacrifice. No region-specific decreases in estrogen binding were observed in either cytosol or nuclear extracts. To further examine possible regional specificity, quantitative autoradiographic analysis of the in vivo hypothalamic uptake of an iodinated analog of estradiol, 11 beta methoxy-16 alpha-[125I]iodoestradiol (MIE2), in OVX rats treated with DDC was conducted. Animals received a saturating dose of [125I]MIE2 12 h after DDC or saline treatment and 1 h before sacrifice. DDC treatment resulted in higher background levels of radioactivity and a trend toward higher uptake levels in all brain regions, but with no evidence of marked regional specific effects in any area of the brain. In tissue uptake studies, DDC treatment resulted in higher levels of radioactivity recovered from serum and neural tissues of [125I]MIE2 injected rats, suggesting that DDC slows the clearance of MIE2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1884220 TI - Instability of motor unit firing rates during prolonged isometric contractions in human masseter. AB - The firing patterns of up to 4 concurrently active masseter motor units were studied with intramuscular electrodes during a continuous isometric contraction of 15 min duration, in which the subject maintained the mean firing rate of one selected unit at 10 Hz. With this paradigm the net excitation (i.e. mean firing rate) of one unit in the muscle was controlled. This served as the reference for the functional state of other active units during the prolonged contraction. With the mean firing rate of one unit in the muscle fixed, 58% of other active units showed a slow, statistically-significant change in mean firing rate over the 15 min. The initial firing rate of the units did not influence the change in rate. The original firing rate hierarchy, which in short-term contractions reflects the recruitment order, was altered during the prolonged contraction. The explanation for these differential changes in motoneuron net excitation is not clear; they could be intrinsic to the motoneurons or perhaps mediated by reflex pathways. The selective facilitation or suppression of some motor units with continuous activation means that the original size-structured combination of motor units can be modified during a prolonged contraction. PMID- 1884221 TI - Oral nociceptive activity in the rat superior colliculus. AB - Single units were recorded using extracellular glass microelectrodes in all laminae of the superior colliculus of the rat under halothane nitrous oxide anaesthesia. Fifty-one units were encountered which responded to a low intensity mechanical stimulus applied to a contralateral or bilateral field located in the oral sphere (intraoral 11, perioral 16), on the face (29) or on the rest of the body (21). Sixteen units responded to a jaw movement. Sixty-one cells were recorded which were preferentially (10) or only (51) activated (30) or inhibited (21) by noxious stimuli. Contralateral or bilateral mechanoreceptive fields located in intraoral (34) and perioral (35) areas were frequent. There is therefore a high incidence of the nociceptive representation of the mouth in the superior colliculus. The other functional properties of the nociceptive units were similar to those reported in other studies. From the subsequent histological localization of the recorded units, it appeared that the nociceptive projections from the intraoral and perioral regions to the superior colliculus reach the lateral part of the intermediate and deep layers of the superior colliculus. PMID- 1884222 TI - Intracerebral distribution of Gp135, a new human brain glycoprotein. AB - The intracerebral distribution of Gp135, a new human membrane glycoprotein, defined by monoclonal antibodies, was determined by a quantitative enzyme-linked immunosorbent assay (ELISA) and the presence in different brain regions was shown by immunohistochemistry. The gray matter of frontal cortex and cerebellum were found to express this antigen in high amounts, whereas the subcortical white matter, pons and medulla oblongata displayed low levels. The presence of Gp135 was visualized in regions in which high density of neuronal dendrites and unmyelinated axons are found. Gp135 may participate in cell adhesion processes, in which cell-cell contacts and tissue integrity are fundamental. PMID- 1884223 TI - Substratum regulation of neurite fasciculation. AB - A new clonal nerve-like cell line from the rat eye is used to show that cell substratum adhesion can modulate neurite fasciculation. When cells are grown on a substratum of intermediate adhesiveness their neurites adhere to each other and form fascicles. In contrast, cells grown on more adhesive surfaces spread and extend individual neurites. The direct relationship between the initial rates of cell-substratum adhesion and neurite fasciculation shows that the extent of axon fasciculation which occurs in vivo may be determined by the extracellular environment through which the axons are growing. PMID- 1884224 TI - Basolateral amygdaloid multi-unit neuronal correlates of discriminative avoidance learning in rabbits. AB - Basolateral (BL) amygdaloid multi-unit activity was recorded as male albino rabbits learned to avoid a foot-shock unconditioned stimulus (US) by stepping in an activity wheel to an acoustic (pure tone) warning stimulus (CS+). A second tone (CS-) of different auditory frequency than the CS+ was presented in an irregular order on half of the conditioning trials but was never followed by the US. BL amygdaloid neurons developed, in the first session of conditioning, enhanced CS-elicited discharges relative to discharges recorded during pretraining with tones and noncontingent US presentations (excitatory plasticity), and greater discharges to the CS+ than to the CS- (discriminative plasticity). The discriminative plasticity attained maximal magnitude as the rabbits reached the asymptote of behavioral discrimination, and persisted during post-asymptotic training. Peak excitatory plasticity occurred in the session of the first significant behavioral discrimination and declined during the asymptotic and post-asymptotic stages of training. Similar patterns of excitatory and discriminative plasticity in structures directly interconnected with the BL nucleus (anterior cingulate cortex; medial dorsal thalamic nucleus) and effects of lesions suggest that the neurons in these areas participate in a circuit involved in mediation of avoidance learning. PMID- 1884225 TI - Alterations of functional glucose use and ligand binding to second messenger systems following unilateral orbital enucleation. AB - Quantitative autoradiography was used to examine the effect of lesioning a well defined glutamatergic system (retinofugal fibres) on [3H]forskolin binding to Gs adenylate cyclase and [3H]PDBu (phorbol-12,13-dibutyrate) binding to protein kinase C (PKC) in the rat visual system at 1, 5, 10 and 20 days after unilateral orbital enucleation. Local cerebral glucose utilisation was determined in the same animals using quantitative [14C]2-deoxyglucose autoradiography. At 5 days post-lesion, [3H]forskolin binding sites were significantly reduced in the visually-deprived superior colliculus (-14 +/- 1%) and dorsal lateral geniculate body (-8 +/- 2%), and these reductions persisted until 20 days post-lesion. There were no significant alterations in the amount of [3H]PDBu binding in any region in the visually-deprived hemisphere following enucleation. Function-related glucose use was significantly reduced throughout the visual pathway after enucleation. In this study, there was no conclusive evidence of plastic modifications of second messenger systems in the rat visual system despite a general depression of visual function following lesion of retinofugal fibres. PMID- 1884226 TI - The ontogeny of transferrin receptors in the embryonic chick retina: an immunohistochemical study. AB - Transferrin receptor (TfR) immunoreactivity in the developing chick retina was examined. Immunoreactivity was detectable in the ganglion cells of embryonic day (E) 4 retina. At E9, diffuse TfR immunoreactivity appeared in the outer portion of the inner nuclear layer. Amacrine cells were the most intensely TfR-positive cells in the inner nuclear layer. At E11, the inner segment of photoreceptor cells showed moderate immunoreactivity. With the appearance of the outer segments, positive immunoreactivity was observed in these structures. TfR's developmental distribution in the retina may reflect the developmental and physiological role of transferrin. PMID- 1884227 TI - Octopamine induces bursting and plateau potentials in insect neurones. AB - The membrane properties of some inter- and motoneurones in the respiratory and flight systems of the locust Locusta migratoria were characterized during octopamine perfusion by means of intracellular recording techniques. Octopamine induced active membrane properties in these neurones. Plateau-potentials were evoked by brief current pulses or synaptic input in 3 of the identified neurones and endogenous bursting was evoked by prolonged current pulses in one identified interneurone. Hyperpolarizing pulses injected into these neurones either prematurely terminated or suppressed these responses, indicating that these potentials are due to active membrane properties intrinsic to these neurones. Such intrinsic membrane properties have not been described in insects before. Further investigations are necessary to examine whether these properties may play an important role in the generation of rhythmic motor patterns as has previously been demonstrated in many other vertebrate and invertebrate motor systems. PMID- 1884228 TI - Lumbar intrathecal morphine alters activity of putative nociceptive modulatory neurons in rostral ventromedial medulla. AB - Two physiologically and pharmacologically distinct classes of putative nociceptive modulatory neurons have been identified in the rostral ventral medulla (RVM) of the lightly anesthetized rat: on-cells and off-cells. We have previously shown that administration of morphine either systemically or by microinjection into the periaqueductal gray (PAG) produces an increase in the activity of all off-cells and a depression of the activity of all on-cells concomitant with inhibition of the tail flick reflex. We now demonstrate that morphine applied intrathecally has effects on RVM neurons that are indistinguishable from those of systemic or PAG administration. This may contribute to the known multiplicative effects of concurrent administration of opioids at spinal and supraspinal sites. PMID- 1884229 TI - A medullary inhibitory region for trigeminal motoneurons in the cat. AB - The present report describes the effects on trigeminal motoneurons of stimulation of a circumscribed site within the parvocellular region of the medullary reticular formation. This medullary site was selected because anatomical studies have shown that premotor interneurons project from this site to the trigeminal motorpool. Electrical stimulation of this site induced IPSPs (PcRF-IPSPs) in jaw closer motoneurons. A population of these IPSPs, recorded contralateral to the site of stimulation, exhibited latencies shorter than 1.5 ms (mean 1.16 +/- 0.08 SD). Their mean amplitude was 1.72 mV +/- 1.13 SD and their mean duration was 3.52 ms +/- 2.15 SD. We believe that these PcRF-IPSPs arose as the result of activation of a monosynaptic pathway. A comparable inhibitory input from this site to ipsilateral jaw-closer motoneurons and to both contra and ipsilateral digastric motoneurons was also observed. We therefore conclude that this medullary PcRF site contains premotor interneurons that are capable of postsynaptically inhibiting motoneurons that innervate antagonistic jaw muscles. PMID- 1884230 TI - Dietary arginine fails to protect against cerebrovascular damage in stroke-prone hypertensive rats. AB - Stroke-prone spontaneously hypertensive rats (SHRSP) develop severe hypertension and cerebrovascular lesions. We investigated the influence of dietary supplementation with L-arginine, an amino acid precursor of endothelium-derived nitric oxide, on blood pressure and stroke in these rats. L-Arginine, administered in the saline drinking solution at 2 or 6 g/l starting at 8.7 weeks of age, was without effect on blood pressure, cerebrovascular lesions, or longevity despite continuous treatment through 14 weeks of age. These findings do not support a beneficial influence of dietary arginine in the cerebrovascular pathology of SHRSP. PMID- 1884231 TI - Enhanced responses to stress induced by fat-feeding in rats: relationship between hypothalamic noradrenaline and blood glucose. AB - High-fat-feeding in rats has been reported to enhance stress reactions, as assessed by elevation of blood glucose and corticosterone levels. This study was designed to investigate the relationship between changes in blood glucose and hypothalamic neuronal noradrenaline activity (HNNA), as indexed by the ratio of dihydroxyphenylethyleneglycol (DHPG) to noradrenaline (NA), following physiological stress in high-fat-fed rats. Two groups of adult male Wistar rats were fed isocaloric diets high in fat (59% of calories) or starch (70% of calories). After 3 weeks each of these groups was further subdivided into (a) control, (b) 2 min ambient temperature (20 degrees C) swim or (c) 2 min swim in ice-cold water. Animals were decapitated 20 min after commencing the swim; trunk blood and a sample of medial basal hypothalamus were obtained. Computerized gas chromatography/mass spectrometry was used to measure hypothalamic DHPG and NA concentrations. There were no differences between fat- and starch-fed rats in basal levels of serum glucose, insulin or corticosterone and no differences in DHPG, NA or DHPG/NA ratio. Compared to starch-fed rats, ambient swim stress in the fat-fed group produced significantly larger serum glucose (P less than 0.01), serum corticosterone (P less than 0.05), DHPG (P less than 0.05) and DHPG/NA (P less than 0.01) responses. Following cold swim stress similar differences between fat- and starch-fed animals were observed. In addition, serum insulin was found to be significantly suppressed in the fat-fed group (P less than 0.05) following cold swim.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1884232 TI - Facilitation of masseter EMG and masseteric (jaw-closure) reflex by serotonin in behaving cats. AB - The trigeminal motor nucleus (MoV) contains the somata of the motoneurons that control jaw position and jaw movements. This nucleus is of neurochemical interest because it receives a dense serotonergic input. We examined the effects of application of serotonin or fluoxetine, a serotonin reuptake blocker, into this nucleus on the spontaneous or reflex (jaw-closure) electrical activity of the masseter muscle in behaving cats. Serotonin produced a clearcut enhancement of both spontaneous and reflex activities. This action was attenuated by previous systemic injection of the serotonin receptor antagonist methysergide. The effect was mimicked to a certain extent by fluoxetine. These data provide evidence that the serotonergic input to MoV exerts a general facilitatory influence on masseter motoneurons activity. PMID- 1884233 TI - The effect of amiloride on taste-evoked activity in the nucleus tractus solitarius of the rat. AB - Amiloride is an inhibitor of passive sodium transport. Its application to taste receptors blocks inward sodium current, suppresses sodium-induced neural activity and reduces the perceived intensity of NaCl. We recorded taste-evoked responses of single neurons in the nucleus tractus solitarius (NTS) of the rat before and after the lingual application of amiloride to determine which neurons would be affected, the degree of the effect and the subsequent form of the neural code for sodium. Responses to all 7 stimuli that contained Na+ or Li+ were suppressed by amiloride. Activity evoked by the 8 other stimuli was unaltered. NTS neurons could be divided into 4 subsets according to their response profiles: Group 1 (salt-sugar), Group 2 (salt), Group 3 (salt-acid) and Group 4 (acid-salt-bitter). The entire effect of amiloride was discharged on cells in Groups 1 and 2; those in Groups 3 and 4 were unaffected. Following amiloride application, the neural code for sodium and lithium salts was highly similar to those for acids, bitter salts and quinine. Thus the activity of neurons in Groups 1 and 2 may be responsible for the distinction between 'saltiness' and sour-bitter tastes. The results imply that specific receptors are responsible for the recognition and transduction of sodium salts and that this specificity is maintained in the peripheral taste nerves to be manifested in the NTS. PMID- 1884234 TI - Increased vasopressin immunoreactivity in the rat brain after a postmortem interval of 6 hours. AB - Enhanced immunocytochemical staining of vasopressin-containing neurons was observed after incubation of rat brain slices in Ringer medium for 6 h at room temperature, as compared to brain tissue fixed immediately after death. Hypothalamic vasopressin neurons in the supraoptic nucleus, the paraventricular nucleus and the suprachiasmatic nucleus stained more intensely after a postmortem interval of 6 h. Extrahypothalamic vasopressin neurons (VP) in the bed nucleus of the stria terminalis, the medial amygdala and the locus coeruleus proved to be stained as well. Extrahypothalamic VP neurons in the locus coeruleus could, until now, only be visualized after in vivo pretreatment with colchicine. In addition, staining was observed at two new sites, the dorsal raphe nucleus and the lateral septum. Staining of VP was corroborated by application of different antibodies directed against the intact vasopressin molecule as well as by antibodies directed against the other parts of the vasopressin precursor molecule, i.e. neurophysin and glycopeptide. The specificity of the VP-staining was validated by using pre-immune serum and using Brattleboro rat brain tissue, resulting in a negative staining in both cases. Furthermore, homogenated punches of the suprachiasmatic nucleus were submitted to iso-electric focussing on polyacrylamide gel, followed by press blotting and subsequent immunocytochemical staining for vasopressin. Iso-electric foccussing enabled us to characterize and quantify peptides in the suprachiasmatic nucleus. The vasopressin content increased 6 h postmortem, while c-terminal glycopeptide and neurophysin levels remained stable. Similar results were observed in the suprachiasmatic nucleus from decapitated rats whose brains were left intact in the skull for 6 h at room temperature. PMID- 1884235 TI - Central neural pathway mediating splanchnic osmosensation. AB - To determine the central neural pathway which carries splanchnic osmosensory information to vasopressin (AVP) neurons in the hypothalamus, bilateral electrolytic lesions were placed in the ascending catecholaminergic fiber bundle, the locus coeruleus (LC), the locus subcoeruleus (subLC), the lateral parabrachial nucleus (LPB), the caudal periaqueductal gray (PAG) and the median preoptic nucleus (MPO). Six and seven days later, plasma AVP levels, plasma osmolality, mean arterial pressure and heart rate were measured following gastric infusion of hypertonic (598 mosm/kg; 2 ml/4 min) or isotonic (290 mosm/kg) saline in conscious rats with indwelling tail artery catheters and nasogastric tubes. The most effective pontine lesions, which were located in the ventral locus subcoeruleus (vsubLC) approximately 1.0 mm below the LC, decreased the AVP response to hypertonic gastric infusion by 59.7% (P less than 0.05) as compared to sham-lesioned controls. In addition, unilateral vsubLC lesions dramatically reduced the catecholamine innervation of the ipsilateral paraventricular nucleus (PVN), as qualitatively determined with dopamine beta-hydroxylase immunocytochemistry, suggesting that a pathway ascending with catecholaminergic fibers was disrupted. Lesions of the MPO were also very effective, decreasing the AVP response to hypertonic saline infusion by 60.3% (P less than 0.05), suggesting that the MPO is an integral relay center in this pathway. On the other hand, LC, LPB and PAG lesions were ineffective. Systemic plasma osmolality or cardiovascular factors did not mediate the AVP response. These results demonstrate, for the first time, that splanchnic osmotic information is transmitted to the hypothalamus via pathways within the ascending catecholaminergic fiber bundles, the MPO is a relay center where peripheral and central osmotic information may be integrated, and the LC, LPB, and PAG are not part of the splanchnic osmotic pathway. PMID- 1884236 TI - Interleukin-1 beta decreases acetylcholine measured by microdialysis in the hippocampus of freely moving rats. AB - Interleukin (IL-1) is a cytokine which plays an important role in the modulation of the acute response in host defense. This cytokine is also increased in patients with Alzheimer's disease. In the present experiment systemic injection of IL-1 beta (7.5-50 micrograms/kg) decreased extracellular acetylcholine in the hippocampus. This effect could not be attributed entirely to general malaise since lithium chloride (130 mg/kg) had the opposite effect. Heat-inactivation of the cytokine eliminated the reduction of extracellular ACh. The results give further evidence of a relationship between the immune system and the central nervous system and suggest a possible relationship between IL-1 and cholinergic function or dysfunction in the hippocampus. PMID- 1884237 TI - Lesions of parvocellular subdivisions of the hypothalamic paraventricular nucleus alter open field behavior and acquisition of sensory and spatial discrimination. AB - Rats with ibotenic acid (IBO) lesions of the hypothalamic paraventricular nucleus (PVN) were compared with operated control animals over a battery of tests designed to assess memory- and arousal-related behavioral processes. At the dose employed in these experiments, ibotenic acid selectively destroys parvocellular elements of the PVN, leaving magnocellular subdivisions relatively intact, allowing for experimental dissection of the influence of parvocellular and magnocellular PVN neuronal populations on the behavioral parameters measured. IBO treated rats showed a greater incidence of rearing behavior and exhibited greater levels of total and central ambulation in an open field than control rats. Acquisition of both the sensory and spatial reward contingencies were retarded in the IBO-lesion group; however, no differences were evident between IBO-treated and control groups in an approach-avoidance test, nor in the ability to perform the spatial and sensory discrimination tasks to a criterion level of accuracy. Histological examination verified that bilateral IBO lesions destroyed parvocellular elements of the PVN, while sparing the majority of magnocellular neurons. Results suggest that parvocellular PVN lesions alter behavioral performance via interactions with physiological systems governing arousal level. PMID- 1884238 TI - Side and region dependent changes in dopamine activation with various durations of restraint stress. AB - Exposure to various mild stressors has been shown to result in the activation of dopamine containing neuronal systems projecting to the medial prefrontal cortex (PFC), to a lesser extent the nucleus accumbens septi/olfactory tubercle (NAS) and, in a few studies, the striatum. It has also been shown that dopamine (DA) systems on different sides of the PFC are successively activated as stressors are prolonged. We have therefore examined the effects of variation in the duration of a restraint stressor (15, 30 and 60 min) on region and side dependent alterations in DA utilization in the PFC, NAS and striatum. Increases in the concentrations of the DA metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and/or homovanillic acid (HVA) or in their ratios with DA were seen in all regions examined with the largest effects occurring in the PFC and lesser effects in the NAS and striatum. In each region, the magnitude of these effects varied with time of restraint exposure. In the PFC, lateralized alterations in HVA and DA were seen over time with effects progressing from a left greater than right involvement at 15 min to a right greater than left involvement at 60 min. These results are discussed with reference to side and region dependent effects on brain DA systems as stressors are prolonged and the implications they may have for lateralized regional brain activity associated with stressor precipitated psychiatric disease. PMID- 1884239 TI - A primary encephalocele culture yields a pure population of human astrocytes. AB - In order to develop a reliable source of human astrocytes for in vitro studies, we established a primary explant culture of a human encephalocele. This culture yielded a population of cells which were karyotypically normal, morphologically resembled astrocytes, expressed glial fibrillary acid protein, and responded mitogenically to exogenous growth factors. We conclude that white matter derived from human encephaloceles can be used to generate pure populations of normal astrocytes. PMID- 1884240 TI - Brain laterality as a determinant of susceptibility to depression in an animal model. AB - Rats exposed to stressors that cannot be controlled may develop a deficit in their ability to subsequently learn to control a new stressor. This phenomenon is known as 'learned helplessness' and is a well-accepted animal model of depression. Evidence is presented showing that rats having different directional biases of brain laterality, as indicated in tests of rotational behavior, differ greatly in their response to stressors and to the lack of stressor control. Differences in brain laterality appear to be an important source of variability within the animal model of depression. As with humans, only some rats are vulnerable to depression-like symptoms. These findings are relevant to biological theories of depression that are based upon lateralized specialization of the human brain for affect. PMID- 1884241 TI - Localization of basic FGF-like immunoreactivity in the hypothalamo-hypophyseal neuroendocrine axis. AB - We examined the localization of basic fibroblast growth factor (basic FGF) in the adult rat brain by immunohistochemical and Western blotting analysis using a specific antibody against a synthetic basic FGF fragment (N-terminal 12 residues). The antibody did not cross-react with acidic FGF. Basic FGF-like immunoreactivity was located exclusively in the neuronal elements and had very heterogeneous distribution. Immunoreactive cell bodies were observed in the paraventricular, supraoptic and circular nuclei of the hypothalamus. Numerous immunoreactive neuronal processes originating from these basic FGF-positive cells extended lateroventrally and then caudally to the internal layer of the median eminence. In addition, the neurohypophysis contained a significant number of basic FGF-like immunoreactive fibers. Western-blotting analysis revealed that the hypothalamus and the hypophysis contained a main band of basic FGF immunoreactive with an apparent molecular weight of 17 kDa. These results show that the hypothalamo-hypophyseal neuroendocrine pathway contains basic FGF. PMID- 1884242 TI - Alcohols synergize with NGF to induce early differentiation of PC12 cells. AB - The role of alcohols in affecting neuromorphogenesis was investigated in a single cell type, pheochromocytoma (PC12). The effect of ethanol at physiological concentrations in this system leads to enhanced morphological and functional differentiation in combination with nerve growth factor (NGF). PC12 cells treated with a suboptimal concentration of NGF (30 ng/ml) and an alcohol (87 mM) underwent rapid morphological differentiation which was dependent upon the side chain length of the alcohol MeOH less than EtOH less than PrOH less than BuOH. Pyrazole at either 5 or 10 mM had no effect on alcohol induced neurite extension. Assessment of the degree of differentiation promoted by the various alcohols was quantified by an increase in neurite extension, a decrease in the incorporation of [3H]thymidine, an increase in acetylcholine esterase (AChE) activity and immunostaining with neuron specific enolase. Thus, alcohols may function in a specific manner by interacting with transmembrane signalling pathways which promote gene expression and neuronal differentiation. PMID- 1884243 TI - Conditioned place preference produced by infusion of Met-enkephalin into the medial preoptic area. AB - The conditioned place preference procedure was used to evaluate the rewarding properties of D-Ala2-Met5-enkephalinamide (DALA) after bilateral infusion into the medial preoptic area. Doses of 60, 250 and 100 ng/cannula were used. It was found that all doses of DALA produced place preference. This suggests that the medial preoptic area is a structure where opioid reward is produced in doses as low as those required in already established reward systems. The significance of this in relation to sexual reward is discussed. PMID- 1884244 TI - Increased effect of noradrenaline on synaptic responses in rat CA1 hippocampal area after adrenalectomy. AB - Pyramidal neurons in the rat CA1 hippocampal area contain intracellular receptors for the steroid hormone corticosterone, and membrane associated alpha- and beta adrenergic receptors. We compared the effect of noradrenaline (NA) on the synaptically evoked CA1 field potential in adrenalectomized (ADX) rats, where corticosteroid receptors are not occupied, with sham-operated controls. It appeared that the increase in the amplitude of the field potential induced by 10 microM NA was more pronounced in slices from ADX rats than in sham operated controls. In vitro application of 30 nM corticosterone (20 min) to slices from ADX rats shifted the NA-evoked increases in synaptic efficacy towards the level of the sham operated rats. The incidence of a secondary population spike after application of NA was increased in slices from ADX rats compared to slices from sham controls or ADX rats treated with corticosterone. Occupation of receptors for corticosterone in the hippocampal CA1 area may therefore potentially lead to suppression of excitability. PMID- 1884245 TI - Effects of clonidine on sympathoexcitatory neurons in the rostral ventrolateral medulla. AB - The effects of intravenous and iontophoretic clonidine were determined on the firing rates of sympathoexcitatory neurons in the rostral ventrolateral medulla of the cat. As previously reported in the rat, we found that sympathoexcitatory neurons could be differentiated based on their sensitivity in clonidine. Approximately 50% of the neurons were inhibited by clonidine. There was only a weak correlation between the inhibition of unit activity and whole sympathetic nerve activity. The discharge rates of the remaining neurons were either not altered or were increased by clonidine. Unlike the rat, these two groups of neurons could not be further differentiated on the basis of axonal conduction velocity or discharge frequency. These data are discussed and the effects of clonidine and 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) on sympathoexcitatory neurons are compared. PMID- 1884246 TI - Feasibility of total body irradiation in chronic lymphocytic leukemia and low grade non-Hodgkin's lymphomas. AB - Combined total body irradiation (TBI) and Prednimustine were prospectively evaluated in 30 patients affected either with chronic lymphocytic leukemia (CLL) or with low-grade non-Hodgkin's lymphoma (NHL) eleven patients were previously treated. Between January 1984 and May 1987, 20 evaluable patients with CLL, median age 66 years (range 43-82), classified according to Rai (4 in stage I, 10 in stage II, 4 in stage III, 2 in stage IV) and 10 evaluable patients with NHL low-grade malignancy according to the Working Formulation, Stages III and IV, median age 54 years (range 32-71) were treated using a 6 MeV Linear Accelerator, applying two opposite alternating fields including total body, with a fraction of 15 cGy, 2 fractions weekly (3-day interval) for a total dose of 150 cGy given over 5 weeks. Prednimustine (100 mg/m2, orally, for 5 consecutive days, every 3-4 weeks, for 6-9 courses) was administered 2 months after TBI treatment, as consolidation therapy. By May 1989, a total of 85% hematological responses (defined as normalization of the differential white cell count, of the total blood cell count and of bone marrow infiltration) were obtained after combined treatment in CLL patients; moreover 3 CR (according to the WHO criteria), 75% with splenomegaly reduction and 40% with lymphadenopathy reduction were seen. Ninety percent objective responses (5 CR and 4 PR) were observed in the NHL patients, with 50% having splenomegaly reduction and 67% lymphadenopathy reduction. The median response time in the two groups was, respectively, 14 and 23 months. The overall toxicity (WHO grades 1,2,3,4) after combined treatment was 65% and 70% in the two patient groups. WHO grade III toxicity, completely reversible, was verified in only 16.6% of the cases; all cases, except one, were previously treated. Additionally, 1 toxic death (grade IV thrombocytopenia and leukopenia) was observed in a heavily pretreated patient affected with CLL after TBI alone. Prednimustine regimen was generally well tolerated. The high response rate and acceptable toxicity, confirms the feasibility and the usefulness of TBI in the context of a combined treatment for CLL and low-grade NHL patients. However in order to further reduce the severe toxic side effects, observed in one patient, white blood cells and platelet count should be plotted and monitored carefully, particularly in pretreated patients. PMID- 1884247 TI - Intracellular dCTP/ara-CTP ratio and the cytotoxic effect of ara-C. AB - In this study, the relationship between the dCTP/ara-CTP ratio and the cytotoxic effect of cytosine arabinoside (ara-C) was investigated. Intracellular levels of dNTPs and ara-CTP were analyzed by high-performance liquid chromatography. Although doubling time and intracellular dCTP levels were different in each of the cells, there was a consistent relation between the intracellular dCTP/ara-CTP ratio and the cytotoxic concentration of ara-C. These data suggest that the intracellular dCTP/ara-CTP ratio is one of the important factors for considering the cytotoxic action of ara-C. PMID- 1884248 TI - The effect of tumor burden on ornithine decarboxylase activity in mice. AB - Polyamines are essential for cell growth of normal and neoplastic tissue, alpha Difluoromethylornithine (DFMO) is a known irreversible inhibitor or ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine biosynthesis. The purpose of this study was to examine the effects of tumor burden on ODC in tissues of tumor-bearing compared with tumor-free mice. Twenty-eight male Balb/c mice were divided into four groups of 7 each. Groups 1 and 2 were inoculated subcutaneously with 10 x 10(6) MC-26 mouse colon adenocarcinoma cells. Groups 3 and 4 were kept as tumor-free controls. Ten days after inoculation, groups 2 and 4 were injected with DFMO (200 mg/kg) intraperitoneally (IP) while Groups 1 and 3 received saline. Two hours after the injection of DFMO the animals were sacrificed. The tumor, pancreas, kidney, and liver were excised and analyzed for ODC activity. DFMO caused a significant reduction (compared with controls that did not receive DFMO) in the ODC activity of tumors; however, ODC activity of the kidney, pancreas, and liver of tumor-bearing mice was not affected. Additionally, the basal ODC activity in the kidney, liver, and pancreas of tumor-bearing mice was significantly lower compared with tumor-free controls. DFMO lowered ODC activity in the kidney, pancreas, and liver of tumor-free mice. These results suggest that the presence of MC-26 tumor causes systemic effects that alter ODC activity and the response to a known inhibitor of ODC. PMID- 1884249 TI - Antioxidants in female breast cancer patients. AB - Blood levels of selenium, zinc, copper, and vitamins E and C were measured in 48 cases and 50 controls from a hospital-based case-control study bearing on breast cancer risk factors in Montpellier (France). Cellular levels of selenium and vitamins E and C were also evaluated in most of the subjects. We found that the blood and cellular levels of these antioxidants were overall higher in cases than in controls, significantly for serum zinc, plasma, and leukocyte vitamin E. The statistical significance of the difference between case and control serum Cu crude levels disappeared after adjustment for metabolically related variables. The difference was borderline significant for leukocyte vitamin C. These results were slightly modified when vitamin pill users were excluded from case and control samples. The serum zinc odds ratios computed after adjustment for related variables were significantly elevated (2.53, confidence interval: 1.34-4.78, for the highest tertile) as were those computed previously for pooled plasma vitamin E levels in a joint study. PMID- 1884250 TI - Tumor suppressor genes and cancer of the human nervous system. PMID- 1884251 TI - The role of mediastinoscopy and anterior mediastinotomy in determining operability of lung cancer: a review of published questions and answers. PMID- 1884252 TI - Recent advances in radiotherapy treatment planning. AB - Radiation treatment planning is currently in a state of rapid change. Dissatisfaction with past planning technology stems from the growing realization that: (1) Increases in the local regional tumor control rate will increase the cure rate in many malignancies. (2) Even at the best treatment centers geometric tumor misses are commonplace. (3) Traditional constraints on treatment techniques, originally imposed for simplicity and reproducibility, are no longer necessary, and can result in suboptimal treatment. (4) Treatment plans judged "optimal" in two dimensions may be far from optimal when viewed over the entire treatment volume. (5) Lack of treatment reproducibility is also commonplace, and can be demonstrated to adversely affect treatment outcome. On the positive side, recent developments in computer graphics, image processing, radiation physics, and radiation biology are now making it possible to define, design, and deliver sophisticated 3D radiation treatments. However, because many of these technologies are being developed for other disciplines, their applicability to radiation therapy treatment planning is not widely appreciated. We outline the current status and new developments in radiation therapy treatment planning. PMID- 1884253 TI - Mediastinoscopy re-examined. PMID- 1884255 TI - Computed tomography manifestations of brucellosis of the sternoclavicular joint. AB - Computed tomography (CT) in three patients with sternoclavicular brucellosis revealed the following features: soft-tissue mass centred around the joint, sclerosis with or without lysis of the periarticular bone, and destruction and irregularity of the cortex of the sternal and clavicular articular surfaces. The CT features, in the appropriate clinical setting, should help in making the correct diagnosis and managing this serious but rare manifestation of brucellosis. PMID- 1884254 TI - Doses and population irradiation factors for Canadian radiation technologists (1978 to 1988). AB - Individual and collective radiation doses received by Canadian radiation technologists (RTs) working in diagnostic radiology, nuclear medicine and radiotherapy are summarized for the period 1978 to 1988. The data were obtained directly from the National Dose Registry, Department of National Health and Welfare. Over the 11-year study period the mean annual dose equivalent fluctuated around 0.2, 1.8 and 1.1 mSv for RTs working in diagnostic radiology, nuclear medicine and radiotherapy respectively. Over the same period the occupational collective dose equivalent decreased in diagnostic radiology (by 44%) and radiotherapy (by 35%) and increased in nuclear medicine (by 45%). Approximately 10,000 RTs are monitored each year, with an estimated total occupational collective dose equivalent of about 3.6 person-sieverts. Analysis of dose distribution data showed that only 1.3% of all monitored RTs received an annual whole-body dose equivalent greater than the current legal limit for members of the public (5 mSv). Approximately half of the RTs working in nuclear medicine and radiotherapy received an annual dose equivalent in excess of 0.5 mSv; only 7.3% of their diagnostic radiology counterparts exceeded this level. Demographic data showed a high preponderance of young women in all three RT classifications, and an analysis of the radiation risks to this occupational group revealed increases of up to 12% above the risk associated with a "standard" adult working population exposed to the same collective dose equivalent. PMID- 1884256 TI - Intra-aortic balloon pumps: an update on radiographic recognition. AB - Intra-aortic balloon pumps increase myocardial perfusion and decrease cardiac afterload in patients with cardiogenic shock and in high-risk patients scheduled for cardiac surgery. Appropriate positioning of the pump can be confirmed in chest radiographs. Familiarity with available catheters helps the physician to recognize overadvancement of the balloon in the ascending aorta or the aortic arch vessels. Because the balloon is long, its position is juxtarenal in most patients. PMID- 1884257 TI - Direct effects of contrast media on rat lungs. AB - Despite the widespread use and the assumed safety of Omnipaque (iohexol) and 3% Gastrografin (meglumine diatrizoate) as contrast media for esophagography and computed tomography respectively, their effects on the lung if they are aspirated have never been studied. This information is important because such compounds may inadvertently enter the lungs during the diagnostic procedures. Twenty-four rats were injected intratracheally with 0.15 mL of one of three contrast agents (omnipaque, full-strength Gastrografin and 3% Gastrografin) or normal saline, which was used as a control. Radiographs were then obtained. Equal numbers from each experimental group were sacrificed after 5 minutes, 1 hour and 24 hours, and their lungs were examined pathologically. The rats injected with full-strength Gastrografin all died immediately of gross pulmonary edema. Neither Omnipaque nor 3% Gastrografin was fatal, but Omnipaque produced more edema and alveolar hemorrhage than either normal saline or 3% Gastrografin. Iohexol is, therefore, more irritating to the airways and the lung parenchyma than previously believed. PMID- 1884258 TI - Embolization of dissecting aneurysms of the petrocavernous segment of the carotid artery. AB - The authors present two patients who had dissecting aneurysms of the petrocavernous segment of the internal carotid artery. They successfully treated the condition with balloon embolization of the artery proximal to the aneurysm. PMID- 1884259 TI - Magnetic resonance imaging of occult vascular malformations of the brain stem. AB - A characteristic appearance of occult cerebrovascular malformations (OCVMs) on high-field spin-echo magnetic resonance imaging (MRI) has been described previously. The authors report a series of 21 of these lesions located in the brain stem and examine the clinical and MRI characteristics. Most of these lesions display a prolonged, fluctuating clinical course, which suggests multiple sclerosis or brain-stem glioma. Although the possibility of hemorrhagic neoplasms mimicking the MRI appearance of OCVMs has been emphasized recently, distinguishing between these two groups of lesions should be possible in most cases. MRI should allow the diagnosis to be made with sufficient certainty to avoid unnecessary intervention for OCVMs in this delicate location. PMID- 1884260 TI - Presacral extramedullary hematopoiesis in thalassemia intermedia. AB - Extramedullary hematopoiesis is manifested by several clinical hematologic disorders including beta-thalassemia major and thalassemia intermedia. We report an unusual case of extramedullary hematopoiesis, which presented as a painful presacral mass in a patient with beta-thalassemia intermedia. The diagnosis was confirmed by a needle biopsy guided by computed tomography. The patient responded well to radiation therapy to the sacral region. PMID- 1884261 TI - Craniospinal magnetic resonance imaging enhanced with Gd-DTPA in von Hippel Lindau disease. AB - The case presented illustrates the utility of enhancement with gadolinium diethylenetriaminepenta-acetic acid in magnetic resonance imaging (MRI) of the brain and the spinal cord in a patient with von Hippel-Lindau disease. The patient had numerous lesions in the brain stem and the cervical and the thoracic spinal cord, most of which were not demonstrated or were only poorly demonstrated with noncontrast MRI. Contrast-enhanced MRI should be performed in two sessions with a separate dose of contrast agent for each. Regular follow-up examinations should be conducted in the same manner. PMID- 1884262 TI - Intracranial meningioma with pulmonary metastases: diagnosis by percutaneous fine needle aspiration biopsy and electron microscopy. AB - The authors report a patient with a history of recurrent intracranial meningiomas in whom two lung nodules developed. A percutaneous fine-needle aspiration biopsy of one nodule demonstrated spindle-form cells; the tumour was specifically diagnosed as metastatic meningioma on the basis of electron microscopic findings. PMID- 1884263 TI - Cecal diverticulitis mimicking appendicitis on ultrasonography. AB - The authors describe a case of acute cecal diverticulitis in which the ultrasonographic features, as well as the clinical features, mimicked those of acute appendicitis. Though rare, acute cecal diverticulitis is an important differential diagnosis when ultrasonographic features suggest acute appendicitis, because the condition can be managed initially without surgery. PMID- 1884264 TI - Residents' corner. Answer to case of the month #8. Diagnosis. Scar carcinoma (adenocarcinoma engulfing calcified tuberculous granulomas) with hemorrhagic brain metastasis. PMID- 1884265 TI - The importance of word choice. PMID- 1884266 TI - [Should it be talked about?]. PMID- 1884267 TI - [Techniques for evaluating the level of pollution in operating rooms due to gaseous or volatile anesthetics]. AB - To evaluate the air pollution in operating rooms when anesthesia is carried out with an open-circuit anesthesia delivery system, two analyzers were tested both in the laboratory and in an operating room. The TIF 5500, a laptop instrument, allows the detection of gas with low ionisation potential such as chloro fluorocarbons (lower detection threshold: 3 ppm). The Bruel & Kjaer 1302 allows the simultaneous determination of the concentrations of the different inhalation anesthetics in the room by photoacoustic spectrometry. For this type of study, the latter proved an excellent instrument. PMID- 1884268 TI - [Autologous transfusion in heart surgery (apropos of 74 patients)]. AB - The present study uses three techniques of autotransfusion in heart surgery under ECC: peroperative and post-ECC transfusion of blood removed after induction of anaesthesia (group I: 25 patients); postoperative transfusion of extravasated thoracic blood (group II: 24 patients) and a combination of the two (group III: 25 patients). Postoperative bleeding was comparable in all groups; A subset likely to haemorrhage made up of patients who had lost more than one litre of blood was isolated and demonstrated a reduction in the number of homologous red cell concentrates needed for the autotransfused population in comparison with the controls (2.4 +/- 2.6 vs 5.7 +/- 3.5 red cell concentrates, p less than 0.05) and was particularly marked in Group II patients who received 1.9 +/- 2.2 homologous red cell concentrates. None of the techniques caused any side-effects. Combination of the two autotransfusion techniques in heart surgery does not secure any additional advantages compared with postoperative autotransfusion alone. PMID- 1884269 TI - [Patient-controlled analgesia in children]. AB - This study describes the author's initial experience with "patient controlled analgesia" (PCA) in thirty school-age children for postoperative pain relief after major orthopedic surgery. The only narcotic used was morphine administered at both continuous and PCA modes. After the first eight patients, dosage regimens were changed and satisfactory postoperative analgesia was obtained in the last 20 patients with few side-effects. Recommended dosages range between 0.1 and 0.2 mg.kg-1 for loading dose, 0.01-0.02 mg.kg-1.h-1 for continuous infusion and 0.01 0.02 mg.kg-1 for PCA dose. Interest and limits of this method in children are discussed. PMID- 1884270 TI - [Nosocomial pneumonia following surgery of esophageal tumors (apropos of 50 cases)]. AB - Esophagus cancer surgery often becomes complicated with fistulas and above all with infections. In 50 cases, the authors relate 7 fistulas and 60 nosocomial infections among which pneumonia takes the first place. The pneumonia diagnosis has been established on the criteria of the "National Nosocomial Infection Study" and on bacteriologic samples. Those mostly isolate Gram-bacilli and streptococci. The diagnosis and etiologic factors leading to prophylactic measures are studied. PMID- 1884271 TI - [The association of continuous peridural anesthesia with general anesthesia. Apropos of 2 accidents]. AB - Continuous lumbar epidural anaesthesia combined with light general anaesthesia provides optimal anaesthetic conditions to realize major lower abdominal or pelvic surgical cases. However this technique may cause haemodynamic alterations due to the important vasoplegia and to the potential myocardial toxicity of the local anaesthetics. The authors report two accidents associated with this technique, one of them with lethal outcome. PMID- 1884272 TI - [The ambulatory anesthesia unit: a problem of organization]. AB - A specialized unit in outpatient anaesthesia and surgery needs an adapted planning. During the preoperative period, it is particularly important to preserve the time of the patients. Different types of structures are possible for the intraoperative period depending on their degree of independence to a hospital. The hospital based unit, with independent facilities, offers various advantages. Its size and its conception must be adapted to the constraints of ambulatory technique, and to the expected needs. During the postoperative period, a special medical organization must be planned to help the patient if necessary. The part of the secretarial work is important for the success of such a unit. Its efficiency may be improved by computerised treatment of part of the information. PMID- 1884273 TI - [Failure of medical treatment with antihypertensive agents in a child with pheochromocytoma. Recovery after surgery]. AB - Anaesthesia for removal of pheochromocytomas requires preoperative preparation of patients so as to normalize blood pressure. During operation, hypovolemia linked with the sudden fall of circulating catecholamines as well as hypertension during handling of the tumor are to be managed. A case of a 11 year child with pheochromocytoma is reported. Once the diagnosis had been established, various attempts to normalize blood pressure failed. Despite a precarious condition, the operation could be performed. During surgery, hypertension occurred and three hypotensive drugs failed to correct it. It ceased after removal of the tumor. The postoperative course was uneventful. The authors discuss the role of the type of catecholamines and their concentration in the failure of antihypertensive medication. PMID- 1884274 TI - [Acute renal insufficiency following a snake bite in a 3-year-old child]. AB - Acute renal failure after viper bite is rare in France. We describe a case in a 3 years-old child, treated with peritoneal dialysis. The physiopathology and the methods of treatment are discussed. PMID- 1884275 TI - [Contribution to a socio-dynamic approach to suicidal behavior: the project of living]. PMID- 1884276 TI - [Deaths from anesthesia in the United States 40 years ago: data and interpretation]. PMID- 1884277 TI - Electroretinogram and visual-evoked potential measurements in sheep. AB - Electroretinogram (ERG) and visual-evoked potential (VEP) recordings were taken from ten Suffolk-cross sheep. Stimuli for VEP were 1.5 flashes of white light/s; ERG stimuli were single flashes. The ERG measurements of the a and b wave latencies and a-to-b amplitude were measured between the lower eyelid and the vertex, with ground on the nuchal crest. The VEP after monocular stimulation were measured between the nuchal crest and the interorbital line, with ground on the vertex. Measurements consisted of the latencies to seven alternating positive and negative peaks P1, N1, P2, N2, P3, N3 and P4, and six amplitudes, P1-N1, N1-P2, P2-N2, N2-P3, P3-N3 and N3-P4. Average latencies for the a and b waves were 13.6 and 28.2 ms; the mean ab amplitude was 131.68 microV. Average latencies for the seven VEP peaks were 35.0, 43.1, 52.8, 64.1, 74.5, 90.4 and 112.2 ms. Mean amplitudes ranged from 3.90 to 8.29 microV. PMID- 1884278 TI - Quantitation of canine plasma von Willebrand factor antigen using a commercial enzyme-linked immunosorbent assay. AB - The purpose of this study was to evaluate a commercial enzyme-linked immunosorbent assay (ELISA) for human von Willebrand factor antigen (vWF:Ag) with respect to its potential value in quantitating the protein in canine plasma. The assay was a sandwich technique using F(ab')2 fragments specific for von Willebrand factor (vWF) and a peroxidase conjugated rabbit anti-vWF second antibody, with a microplate as the support surface. Canine plasmas were assayed by ELISA, and by Laurell electroimmunoassay (EIA), our reference methodology. The ELISA had a within-day variation of 1.21-4.44% and a between-day variation of 0.85-4.88% depending on the level of vWF:Ag. The sensitivity of the assay was less than 0.1% vWF:Ag. The range of vWF:Ag concentrations in plasmas from 24 clinically normal dogs compared favorably with the range for the same plasmas when assayed by EIA (ELISA = 60-152% of normal; EIA = 50-142% of normal). In 121 canine plasmas with vWF:Ag concentrations (as assessed by EIA) ranging from undetectable levels (less than 6% of normal) to 142% of normal, there was good correlation with measurements made by ELISA (correlation coefficient = 0.835). It was concluded that this commercial ELISA technique could be used to provide reliable, same-day measurements of canine plasma vWF:Ag. Since it requires no special equipment other than a microplate reader and washer it is particularly suitable for laboratories lacking the electrophoretic expertise or equipment required for EIA. PMID- 1884279 TI - Pulmonary structure and function in adult dairy cows with an expanded lung field. AB - Pulmonary function tests were performed on seven adult dairy cows with an expanded lung field (ExLF) and the results were compared to the values from seven cows with normal lung fields. The cows with ExLF had an increased functional residual capacity (FRC) and end-tidal N2 concentration of the final breath of the multiple-breath N2 washout (FETN2,fb), and an abnormal distribution of ventilation. The measurements of ventilation and gas exchange and pulmonary mechanics did not differ between the two groups. Postmortem examination of the lungs of five of the cows in each group indicated the cows with ExLF had a bronchiolitis with varying degrees of goblet cell hyperplasia, epithelial cell hyperplasia and metaplasia, smooth muscle hypertrophy, inflammatory cell infiltrate, vascular thickening, peribronchiolar fibrosis, and a mild overinflation of the lung. A histopathological score, based on the preceding indices and bronchus-associated lymphoid tissue, was correlated with FRC, FETN2,fb, the lung clearance index and pulmonary resistance. There were no correlations between the histopathological score and any of the measures of ventilation and gas exchange. PMID- 1884280 TI - Clinical signs, laboratory changes and toxicokinetics of brodifacoum in the horse. AB - Six horses gavaged with a commercial brodifacoum (BDF)-containing bait (Talone) at a dosage of 0.125 mg of BDF/kg of body weight showed weight loss, severe hypocoagulability and hemogram alterations. Four of the horses became depressed and anorectic; one required vitamin K1 therapy. Increases in clotting times were observed at 24 h in the partial thromboplastin time (PTT) followed by the thrombotest (TBT) and one-stage prothrombin time (PT) at 48 h. Elevated mean PTT, PT and TBT were observed from days 4 to 8 (p less than 0.05) with levels returning to pretreatment levels by day 12. Maximum prolongation was a fourfold increase in PTT (day 4), a 2.5-fold increase in TBT (day 6) and a twofold increase in PT (day 6). Thrombin clotting times remained unchanged. In two horses prolongation in clotting time did not normalize until day 23. The mean hematocrit (0.38 +/- 0.01 L/L) was decreased (p less than 0.05) from day 8 (0.33 +/- 0.02 L/L) to day 14 (0.33 +/- 0.01 L/L). The hemoglobin concentration and erythrocyte numbers were decreased (p less than 0.05) from day 6 (20.1%, 17.6% respectively) to day 14 (22%, 20% respectively). Platelet counts decreased on day 6 (17.2%) to nine (14.6%). No other significant changes were observed in routine hematological and serum biochemical parameters. Peak plasma concentrations of BDF occurred 2 to 3 h after oral administration; two horses had detectable levels of BDF at nine days. Pharmacokinetic evaluation indicated that BDF has a half-life of 1.22 +/- 0.22 days, a body clearance of 1073.1 +/- 53.21 mL/kg/day, a volume of distribution of 1853.7 +/- 26.41 ng-day/mL and closely approximates a one compartment model in the elimination phase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1884281 TI - Pharmacological relaxation of the urethra in male cats: a study of the effects of phenoxybenzamine, diazepam, nifedipine and xylazine. AB - Urethral pressure profiles (UPPs) were recorded in ten adult healthy male cats before and after administration of either phenoxybenzamine, diazepam, nifedipine or xylazine. A significant decrease (p less than 0.05) in urethral pressure at the level of the prostate was observed following treatment with all drugs. Xylazine produced a significant decrease in urethral pressure 4 to 7 cm from the tip of the penis in healthy male cats. None of the drugs used decreased urethral pressure in the zones of pure striated muscle or pure smooth muscle in these cats, making current recommendations for pharmacological management of urethral spasm suspect. Further studies are necessary to evaluate clinical cases of urethral spasm and to study the effects of these drugs on the urethral pressure of cats suffering from this spasm. PMID- 1884282 TI - Cross protection among Haemophilus parasuis strains in immunized gnotobiotic pigs. AB - In an attempt to establish if cross protection can be induced by different strains of Haemophilus parasuis, three groups of 12 gnotobiotic pigs were immunized each with an aluminum hydroxide adsorbed whole cell bacterin of one of three H. parasuis strains. Two weeks later, four pigs within each vaccinated group were challenged with aerosols of live cultures of each of the three test strains and observed for response. Two virulent strains V1 and V2 protected all the vaccinated pigs, while all nonvaccinated controls succumbed to Glasser's disease when challenged with these strains. Vaccination with strain LV (of low virulence) protected the pigs against challenge with strain V2, but not against strain V1. Strain LV did not cause disease in the immunized animals and only in one of ten nonimmunized pigs upon second challenge. The results suggest that strains may differ in antigenicity and that virulence and immunoprotection are positively related. Strains to be used in commercial vaccines should therefore be selected carefully. Antibodies detected in the sera of vaccinated pigs were to outer membrane proteins of the bacteria, but not to lipopolysaccharides or capsular polysaccharides. This would suggest that for gnotobiotic pigs outer membrane proteins are more immunogenic than lipopolysaccharide or capsular antigens. Further work is needed to determine if outer membrane proteins also contribute protective immunogens. PMID- 1884283 TI - Histological changes in the nasal ventral conchae of piglets infected with Bordetella bronchiseptica. AB - Piglets infected intranasally with Bordetella bronchiseptica were injected with two fluorochrome markers. Transverse sections of undecalcified nasal conchae (cut between the third incisor and the third premolar teeth) were examined by microradiography and fluorescence microscopy; surface-stained sections were evaluated by light microscopy. The fluorescent surface of the nasal ventral conchae from the infected piglets was increased as compared with the controls. This was due to an increased amount of fluorescent mineralization fronts as well as to the presence of abnormal fluorescent areas within trabeculae. Trabecular mineral content of the microradiographs was irregular and varied from hypo- to hypermineralized. When compared with the corresponding surface-stained sections, no correlation could be made between the mineral content and the type of tissue. These findings suggest that an increased number of osteoblasts which secrete prebone matrix but are modified so that mineralization does not occur normally. PMID- 1884284 TI - Circadian rhythms of osteocalcin in equine serum. Correlation with alkaline phosphatase, calcium, phosphate and total protein levels. AB - The purpose of the study was to determine whether there were circadian variations in serum osteocalcin in normal horses and to determine whether it was important to regulate the time of blood sampling in clinical investigations. Osteocalcin or bone Gla-protein (BGP), alkaline phosphatase, total calcium, phosphate and total protein were studied over a 24 h period. Blood samples were taken every 60 min from nine adult Standardbred horses. There was a correlation between serum levels of alkaline phosphatase (r = 0.3, p less than 0.01), phosphate (r = 0.42, p less than 0.01) and serum osteocalcin levels. There was a very marked individual effect on serum levels of osteocalcin and alkaline phosphatase (p less than 0.01). This effect was present for phosphate levels but not significant for total calcium. The individual effect was lower and time effect was higher for serum osteocalcin if the subjects were divided into two age groups, one of horses of five years or less (n = 4) and a second group older than five years (n = 5). In both groups a circadian rhythmicity was observed. Serum osteocalcin showed a biphasic pattern. Levels were constant during daytime (light period) and underwent significant variations during the night (dark period), going through a nadir at 2000 h and through a maximum peak at 0500 h. It was concluded that in normal horses the blood osteocalcin level follows a circadian variation. Also daytime (light period) seems to be the more appropriate period for blood sampling. PMID- 1884285 TI - Use of a protected catheter brush for culture of the lower respiratory tract in horses with small airway disease. AB - A protected catheter brush introduced by fiberoptic bronchoscopy was used to sample the tracheai and bronchial mucosa in 28 horses with small airway disease. Tracheal and bronchial brushings were examined for the presence of fungi, aerobic and anaerobic bacteria, and a cytoiogical evaluation was also done on fluid collected by the bronchoalveolar lavage (BAL) technique. Microorganisms (bacteria and fungi) were isolated more often in tracheal brushings (53.6%) than in bronchial brushings (10.7%). Anaerobic bacteria were not isolated. Results of this study indicate that fiberoptic bronchoscopy using a protected catheter brush is an easy and practical technique to obtain minimally contaminated samples for isolation of microorganisms from the lower respiratory tract of horses. However, no association was observed between isolation of high numbers of microorganisms from the bronchi and severity of small airway disease. PMID- 1884286 TI - Study of cystine urinary calculi in dogs. AB - The composition and structure of 48 canine cystine urinary stones were determined by infrared spectroscopy, scanning electron microscopy and electron dispersive X ray analysis. The infrared analysis showed that about 45% of the specimens were composed of pure cystine. The remainder also contained calcium oxalate (mono and/or dihydrate), magnesium ammonium phosphate hexadydrate (struvite), calcium hydrogen phosphate dihydrate (brushite) and complex urates (ammonium, ammonium potassium and/or potassium enriched ammonium urate). The infrared study of several samples heated at 620 degrees C and 750 degrees C revealed the presence of apatitic calcium phosphate. This compound was difficult to detect in the spectrum of the original samples due to the small proportion of phosphate contained in the calculi and to band overlapping. The examination of a series of selected samples by means of scanning electron microscopy and energy dispersive X ray analysis complemented the infrared results. PMID- 1884287 TI - A new type of lesion associated with severe fur damage in Canadian ranch foxes and an investigation of possible causes. AB - In the silver fox, as in its wild ancestor, the red fox (Vulpes vulpes L.), the annual growing phase (anagen) of guard hair follicles occupies at least four months. Severe damage to the hair coat near the end of this growing period was reported in 1985 on many ranches in New Brunswick and Nova Scotia. A histological analysis of serial sections of skin biopsies showed a marked increase in nuclear aberrations in the hair matrix of anagen guard hair follicles. These nuclear aberrations indicated that cells were undergoing apoptosis, a controlled form of cell death. Tissues from affected and unaffected foxes for histological and toxicological analysis, as well as other data, were obtained during visits to 26 ranches in 1986 and 34 ranches in 1987. Histological sections of the 1987 skin samples showed the mean percentage of nuclear aberrations in 43 unaffected foxes to be 0.08 +/- 0.01 (SEM), while that for 49 affected foxes was 0.51 +/- 0.23. The four foxes with the most severe coat damage also had the highest incidences of guard hair matrix cells with nuclear aberrations, ranging from 20 to 100 times greater than the mean for unaffected foxes. The mitotic index of the hair matrix, which normally remains fairly constant during the hair growth phase, was similar for unaffected and affected foxes (1.83 +/- 0.06 and 1.97 +/- 0.07 respectively). Although our analyses of field data have not established a specific environmental factor associated with increased nuclear aberrations, the possible involvement of toxic agents in follicle damage may warrant further investigation. PMID- 1884289 TI - Eosinophilic myositis in Canadian cattle. AB - Musculature from 198 Canadian cattle with suspected lesions of eosinophilic myositis were examined histologically and by pepsin digestion. Sera from 51 of the 198 animals were also examined by enzyme-linked immunosorbent assay (ELISA) for anti-Trichinella antibodies. Viable larvae of Trichinella were not recovered from any of the cattle but one animal from Ontario tested positive for anti Trichinella antibodies. Histologically, focal and/or diffuse eosinophilic myositis lesions were observed in 149 (75.2%) of the animals studied. Other conditions identified were sarcocystiosis, abscesses, cysticercosis, steatosis, fibrosis, granuloma, lymphosarcoma and necrosis. Sarcocystiosis was identified in 105 of the 198 animals in both normal and affected musculature. The study indicates that trichinosis is not a primary cause of eosinophilic myositis in cattle. PMID- 1884288 TI - Pulsed radio frequency therapy of experimentally induced arthritis in ponies. AB - The effect of pulsed radio frequency therapy (PRFT) was evaluated on seven ponies with no arthritis and in 28 ponies in which arthritis was created using intra articular amphotericin B to induce synovitis in the right middle carpal joint. The ponies were divided into five treatment and two control groups. Two levels of arthritis were created and two dosage levels of PRFT were evaluated. The effect of PRFT on arthritic and nonarthritic joints was measured by comparing synovial fluid parameters, the degree and duration of lameness, the range of carpal motion, and carpus circumference, for treated and untreated groups. Lesions seen radiographically, at gross pathology, and by histopathology were also compared between the treated and control groups. In the ponies with a mild form of induced arthritis, PRFT significantly (p less than 0.05) reduced the severity and duration of lameness, swelling of the carpus, and the severity of gross pathological and radiographic changes. In these ponies the synovial acid phosphatase levels were lower, the mucin clot quality was superior, and the synovial protein levels were lower for the ponies receiving PRFT as compared to the arthritic ponies receiving no treatment. A dose response effect was evident. In ponies with a slightly more severe form of arthritis, PRFT was evaluated at one dosage level. The treated ponies were significantly improved over the untreated ponies with respect to carpal range of motion, degree of lameness, carpus swelling, and radiographic lesions. No deleterious effects were noted when normal, PRFT treated, middle carpal joints were compared to contralateral untreated, normal joints. It was concluded that significant beneficial effects resulted when affected ponies were treated with PRFT. PMID- 1884290 TI - Comparative hemodynamic effects of halothane and halothane-acepromazine at equipotent doses in dogs. AB - The purpose of this study was to compare the cardiovascular effects of halothane when used alone at increasing doses (1.2, 1.45 and 1.7 minimum alveolar concentration, MAC) to those produced with equipotent doses of halothane after potentiation of the anesthetic effect with acepromazine (ACP) sedation (45% reduction of halothane MAC). Six healthy mature dogs were used on three occasions. The treatments were halothane and intramuscular (IM) saline (1.0 mL), halothane and ACP (0.04 mg/kg IM), or halothane and ACP (0.2 mg/kg IM). Anesthesia was induced and maintained with halothane in oxygen and the dogs were prepared for the collection of arterial and mixed venous blood and for the determination of heart rate, systolic, diastolic and mean arterial pressure, mean pulmonary arterial pressure (PAP), central venous pressure and cardiac output. Following animal preparation the saline or ACP was administered and positive pressure ventilation instituted. Twenty-five minutes later the dogs were exposed to the first of three anesthetic levels, with random assignment of the sequence of administration. At each anesthetic level, measurements were obtained at 20 and 35 min. Calculated values included cardiac index, stroke index, left ventricular work, systemic vascular resistance, arterial oxygen content, mixed venous oxygen content, oxygen delivery and oxygen consumption. Heart rate was significantly higher with halothane alone than with both halothane-ACP combinations and was significantly higher with high dose ACP compared to low dose ACP. Systolic and mean blood pressures were lowest with halothane alone and highest with 0.2 mg/kg ACP, the differences being significant for each treatment. Oxygen uptake and PAP were significantly lower in dogs treated with ACP. It was concluded that ACP does not potentiate the cardiovascular depression that accompanies halothane anesthesia when the resultant lower dose requirements of halothane are taken into consideration. PMID- 1884291 TI - Effect of enrofloxacin on digoxin clearance and steady-state serum concentrations in dogs. AB - The effect of enrofloxacin on the oral clearance and steady-state concentrations of digoxin in serum was evaluated in dogs. Digoxin was administered orally to six healthy adult Beagle dogs following a multiple-dose regimen of 0.0625 mg every 12 h for 23 days. From days 14 to 23 enrofloxacin was administered orally at a dosage of 2.5 mg/kg every 12 h, with subjects receiving enrofloxacin 2 h prior to digoxin. Trough serum concentrations of digoxin were measured using an immunoassay technique. On days 13 and 22, dogs were catheterized for multiple blood sample collection during the 12 h digoxin dosing interval and serum samples were analyzed for digoxin concentrations. In general, steady-state digoxin concentrations in trough serum were not significantly different during enrofloxacin treatment than before enrofloxacin administration. Similarly, digoxin oral clearance was not significantly different between pre-enrofloxacin and digoxin + enrofloxacin periods. We conclude that enrofloxacin is unlikely to have a significant impact on digoxin disposition in dogs. PMID- 1884292 TI - A model for demonstrating the adhesion of Actinobacillus seminis to epithelial cells. AB - The objective of this study was to demonstrate that a field isolate of Actinobacillus seminis (As8C) will adhere to epithelial cells and that this adhesion can be inhibited by pretreating the bacteria with mouse serum containing polyclonal antibodies (PoAbs) prepared against this isolate. An indirect fluorescent antibody test, transmission electron microscopy, and phase-contrast microscopy confirmed the adhesion of As8C to an established culture of bovine kidney epithelial cells (BKECs). In a bacterial adhesion assay, 40 As8C were estimated to adhere to each BKEC after 60 min. Using a bacterial inhibition assay, PoAbs diluted 10(-2) or 10(-3) inhibited the adhesion of As8C to BKECs by approximately 90%. Bacterial inhibition decreased to about 50% when the PoAbs were diluted to 10(-4). There was less than 10% inhibition of adhesion of As8C to BKECs when higher dilutions of PoAbs were used. The inhibition of As8C adhesion to BKECs was less than 20% following pretreatment of BKECs with 10(-2) to 10(-5) dilutions of PoAbs. Moreover, pretreatment of As8C with a 10(-2) dilution of PoAbs did not appear to adversely affect bacterial growth on agar. It is likely that the PoAbs interrupted the adhesion of As8C to BKECs by sterically interfering with a bacterial adhesin-epithelial cell receptor interaction. PMID- 1884293 TI - The seroprevalence of coxiellosis (Q fever) in Ontario sheep flocks. AB - A serological survey for Coxiella burnetii was undertaken on a randomly selected population of 103 Ontario sheep flocks. Twenty-two flocks had at least one positive ewe; seven flocks had two or more reactors. The positive flocks were geographically clustered northwest of Guelph. Crutch-clipping of the ewe's wool prior to lambing, and total confinement housing at lambing in winter and spring seemed to lower the probability of seroreactivity of the flock (p less than 0.05). The study suggests that sheep are not a major reservoir for Coxiella burnetii in Ontario. PMID- 1884294 TI - Effects of interferents on the kinetic Jaffe reaction and an enzymatic colorimetric test for serum creatinine concentration determination in cats, cows, dogs and horses. AB - The effects of acetoacetic acid, acetone, bilirubin, beta-carotene, three cephalospoprin antibiotics, glucose, hemoglobin and lipid on the kinetic Jaffe reaction and an enzymatic reaction for the determination of creatinine concentration were studied in bovine, canine, feline and equine serum. There were no obvious species' differences. The kinetic Jaffe reaction was unaffected by the addition of beta-carotene and hemoglobin. Acetone, cefazolin, cefoxitin, ceftiofur and glucose caused a positive bias while acetoacetic acid, bilirubin, and lipid caused a negative bias when added to the kinetic Jaffe reaction. The enzymatic reaction was unaffected by the addition of acetoacetic acid, acetone, beta-carotene, cefazolin, cefoxitin, glucose and hemoglobin while added lipid, bilirubin and ceftiofur caused a negative bias in the test results. Over all species and interferents, there was no difference in the precision of the two assay methods. In a series of sera from hospitalized patients, the two methods were highly correlated in a linear fashion. The enzymatic creatinine assay deals effectively with most interferents but has a greater cost and shorter shelf-life compared with the kinetic Jaffe reaction. PMID- 1884295 TI - Endometrial biopsy in Holstein-Friesian dairy cows. I. Technique, histological criteria and results. AB - Endometrial biopsies were taken for histological assessment from 97 cows which calved in a commercial dairy herd between April and August 1984. Sixty-two cows were biopsied at both day 26 and 40 postpartum, 23 cows at only day 26, and 12 at day 40 only. Subjective and quantitative histological criteria were assessed. Ninety-five percent of biopsies were adequate for at least subjective assessment. The distribution of criteria within each horn-day category, as well as combined readings by day and by gravid or nongravid horn were computed and significant differences noted. There was more severe inflammation and more segmented cells at day 26 than 40 postpartum, and in the gravid compared to the nongravid horn. The distribution patterns for the criteria examined provide an overview of histological characteristics in this group of postpartum cows. PMID- 1884296 TI - Endometrial biopsy in Holstein-Friesian dairy cows. II. Correlations between histological criteria. AB - Endometrial biopsies were taken for histological assessment from 97 cows which calved in a commercial dairy herd between April and August 1984. The main objectives of this study were to analyze the interrelationships among histological criteria and to identify a shortlist of histological parameters to be included in subsequent analysis of associations with results of bacteriological culture, clinical findings and reproductive performance. Epithelial height and segmented cell counts were highly correlated within biopsy, between horns and between days. Subjective assessment of inflammation in the epithelium and/or stratum compactum generally identified biopsies which had any inflammation present. Cows which had inflammation in a biopsy from day 26 were likely to show inflammatory changes at day 40. Quantitative and subjective assessments of gland number, dilation and fibrosis were highly correlated. There was a positive association between the number of cross sections and the diameter of glands, and both of these criteria were negatively correlated with fibrosis and inflammatory changes. There may be different functional significance of the same histological finding at a different number of days postpartum. PMID- 1884297 TI - Endometrial biopsy in Holstein-Friesian dairy cows. III. Bacteriological analysis and correlations with histological findings. AB - This study examines the results of bacterial culture from 159 endometrial biopsy samples from 97 commercial dairy cows and correlations between bacteriological and histological findings. Bacteria were isolated from approximately 80% of biopsies taken at day 26 and day 40 postpartum. Eleven percent of biopsies were positive for both aerobic and anaerobic culture. Streptococci, Escherichia coli and Actinomyces pyogenes were the most common isolates. Isolation of A. pyogenes from a biopsy at day 26 was positively correlated with isolation of anaerobic bacteria and segmented cell inflammation in the same biopsy, and with subsequent isolation of A. pyogenes at day 40. There was a strong association between isolation of A. pyogenes and anaerobes at day 26 with increased uterine lesions at day 40. Isolation of alpha hemolytic streptococci (AHS) was negatively correlated with isolation of A. pyogenes and with inflammation. Actinomyces pyogenes and AHS showed opposite associations with mononuclear cell inflammation and lymphocytic foci. PMID- 1884298 TI - A survey of biological productivity of Prince Edward Island swine herds. AB - Sow and feeder pig productivity were measured on a random sample of 32 Prince Edward Island swine farms (each producing over 1000 market hogs per year). Productivity parameters could be arranged in a hierarchy, with the highest level on farrow-finish operations represented by pigs weaned per sow per year. The 17 farrow-finish farms in this study averaged 19.6 (+/- 2.2 SD) pigs weaned per sow per year. Large variation between farms was observed with a range from 16.2 to 24.9 pigs weaned per sow per year. The major opportunities for improving productivity, as compared to reviewed targets, lie in reducing the average weaning age, reducing preweaning mortality, and reducing non-productive sow days per parity. The 14 feeder operations were characterized by 0.58 +/- 0.07 kg average daily gain. Average daily gain was negatively correlated with mortality (r = -0.662, p = 0.010), suggesting that herds that achieved a high rate of gain also had lower mortality. PMID- 1884299 TI - A prospective study of sow mortality in breeding herds. AB - This investigation was conducted to study the incidence and the causes of sow mortality in breeding herds. Data were obtained from 24 swine breeding herds with an average inventory of 3755 sows and served gilts for the total sample. Producers were involved for 12 consecutive months and agreed to submit to the diagnostic laboratory every dead or moribund sow and served gilt. The average herd death rate was 3.3% +/- 0.5 (SEM), but varied considerably among herds, ranging from 0% to 9.2%. A total of 137 sows and mated gilts died during the year, and these females had produced an average of 4.2 litters +/- 0.2 (SEM). The number of deaths was significantly higher during the months of July, August and October. The peripartum period appeared to be when sows were most at risk, with 42% of all deaths occurring during this short period of the reproductive cycle. The three major causes of death were heart failure (31.4%), torsions and accidents of abdominal organs (15.3%) and cystitis-pyelonephritis (8.0%). Other causes included endometritis (6.6%), uterine prolapses (6.6%), pneumonia (3.6%), gastric ulcers (3.6%), downer sow syndrome (2.2%), miscellaneous (8.0%) and unknown (14.6%). PMID- 1884300 TI - Doppler-derived velocity of blood flow across the cardiac valves in the normal dog. AB - Doppler echocardiography is a relatively new procedure used to assess certain cardiovascular disorders in the dog. The objectives of this study were to determine the range of values for the maximal peak velocity of blood flow across each of the four cardiac valves in a sample population of normal adult dogs, using duplex continuous wave Doppler echocardiography, and to determine the optimal tomographic planes to use for an adequate continuous wave Doppler evaluation of the canine heart. Twenty normal dogs were examined to obtain values for peak transvalvular velocity for each of the four cardiac valves. The mean values +/- 1 SD, in cm/s were: 98.1 +/- 9.4 for the pulmonary valve imaged from the left side of the chest, 95.5 +/- 10.3 for the pulmonary valve imaged from the right side of the chest (n = 19), 118.1 +/- 10.8 for the aortic valve, 86.2 +/- 9.5 for the mitral valve and 68.9 +/- 8.4 for the tricuspid valve. Regurgitation was detected across the pulmonic valve in 14 of the 20 dogs, and across the tricuspid valve in ten dogs. The analysis of the tomographic images confirmed that for a complete assessment of a given intracardiac valve, the valve must be examined from all possible directions to obtain maximum values for peak velocity. PMID- 1884301 TI - Oxygen radical production by avian leukocytes. AB - Oxygen radical production by heterophils of red-tailed hawks and chickens, and by neutrophils of calves, was evaluated in a chemiluminescence microassay. Leukocytes were isolated by centrifugation of blood in capillary tubes and then challenged with opsonized zymosan in the presence of luminol. Avian heterophils produced significantly fewer oxygen radicals than did bovine neutrophils. PMID- 1884302 TI - Observations on intramammary infection and somatic cell counts in cows treated with recombinant bovine somatotropin. AB - Data were collected on udder health variables as part of a study of the effects of recombinant bovine somatotropin on production in lactating dairy cows. Milk samples, obtained at three intervals during the study, were assessed for their somatic cell count and bacteriological culture result. There was an increase in the prevalence of infection at mid-lactation in the 20.6 and 41.2 mg per day treatment groups as compared to the controls. There was no difference detected in the mean cell count between groups from the samples collected pretrial, mid lactation, or late lactation. However, analysis of the individual cow Dairy Herd Improvement somatic cell count data showed a difference between groups which was most evident in mid-lactation. PMID- 1884303 TI - Women's perception of teratogenic risk. PMID- 1884304 TI - Risk perception of prescription drugs: report on a survey in Canada. PMID- 1884305 TI - On the use of coercion in public health. PMID- 1884306 TI - Sexual behaviour changes in a cohort of male sexual contacts of men with HIV disease: a three-year overview. AB - We describe the sexual behaviour reported by 240 seronegative and seropositive homosexual men over a 3-year period. Sexual partners of men with HIV disease were recruited into a prospective study between July 1984 and July 1985 and were monitored every 3 months thereafter. Data on sexual activities were collected through interviewer-administered questionnaires. The cohort experienced a reduction in both the number of sexual partners and the volume of sexual activity. Reductions in the number of partners were early and dramatic. Changes in sexual activities were gradual and consistent in trend. The greatest reduction occurred in high risk activities (receptive and insertive anal intercourse). After 3 years of follow-up, only 10% of the men continue to be exposed to semen through unprotected receptive anal intercourse and 18% through unprotected receptive oral-genital sex. The proportion of men engaging in oral-genital contact and masturbation remained stable over the 3 years. Once informed of their serostatus, both seropositive and seronegative men reduced their high risk behaviour. The decline in rates of STDs and seroconversion confirmed that this cohort had indeed reduced their high risk behaviour. PMID- 1884307 TI - Re: Last JM. The demographic trap and sustainable health. PMID- 1884308 TI - Predictors of pesticide poisoning. AB - The analysis of 1,026 reports of suspected pesticide poisonings to the regional Poison Control Centre at the Hospital for Sick Children, Toronto consisted of 597 (58.2%) cases less than six years of age. Age was the strongest predictor: there was a risk of 3.1 that young children would encounter rodenticide poisoning compared to that of insecticides; a ten-fold risk of having symptoms from pesticide poisoning if the victim was over five years of age; an increased risk of 5.9 of exposure to moderate or large amounts of pesticide, compared to small quantities, for those over five years of age; and there was less treatment referral for young children, and a 5.7 risk of being referred if the victim was over the age of five years. Other significant predictor variables include the type of person making the inquiry (lay or physician/nurse), the calendar season of the event, and the location (metropolitan or nonmetropolitan) of the event. PMID- 1884309 TI - The role of the nurse-examiner in the National Breast Screening Study. AB - The National Breast Screening Study employed 75 nurse-examiners in 12 screening centres across Canada who screened 67,740 women, some of whom received up to 5 annual screening examinations. 17 nurses each performed more than 5,000 physical examinations of the breast, 38 performed 1,000-4,999 and 20 performed less than 1,000. The nurses' accomplishments were impressive: they taught women how to perform breast self-examination and collected data evaluating BSE compliance, they alleviated anxiety in frightened women, they transmitted and explained clinical information to women who had abnormal screening examinations and they enhanced communication between the NBSS and the family physicians. The excellence of their physical examinations is reflected by a sensitivity of 77-83% for all but one screen years in women age 50-59 assigned to physical examination as a single screening modality and by the cancer detection rates which were achieved. Consequently, we recommend that in the future nurse-examiners should be employed in breast screening centres. PMID- 1884310 TI - The Screening Mammography Program of British Columbia: pilot study. AB - A government-funded pilot project of high volume screening mammography was conducted in Vancouver, British Columbia. 7,100 women were screened over a 9 month period, averaging 43 women per day at a cost of $33.81 per woman screened. 722 (10%) had abnormal mammograms; 144 received breast biopsies; and 29 were diagnosed with cancer. The overall cancer detection rate was 4.1 per 1,000 (0.8 and 4.8 for incident and prevalent cases, respectively). The staging distribution for the 29 cancer cases was 5, 15, 8 and 1 for in situ, stage I, II and III, respectively. PMID- 1884311 TI - [Mortality due to cancers of the brain and lymphatic tissues and leukemia as a function of agriculture pesticide use in Quebec (1976-1985)]. AB - Potential hazards associated with the use of agricultural pesticides are a growing concern for society. We describe the relationships between the mortality data for cancers of the brain, the lymphatic tissues and leukemia, and the spatial distribution of agricultural pesticide use for 34 drainage basins in Quebec, from 1976-1985. The basins were grouped into three categories (low, intermediate, and high exposure) according to the level of sales of pesticides. For cancers of the lymphatic tissues among women 35 to 64 years of age, a high relative risk (RR) was observed (RR = 1.91, 95% Confidence Interval = 1.14, 3.18) in basins highly exposed to pesticides compared to those with low exposure. Analysis of correlation for this cancer at 34 basins showed significant associations between geographical distributions of the Standardized Mortality Ratio (SMR) and those of numerous variables indicative of pesticide use in agriculture. Agreement between the results for mortality data in this exploratory study and the results from another study on cancer incidence data for 1982-1983, supports the hypothesis of a potential relationship between the use of pesticides in agriculture and cancer of the lymphatic tissues. PMID- 1884312 TI - Evaluation of a community health representative program among the Cree of northern Quebec. AB - The James Bay Cree Community Health Representative (CHR) program was implemented in 1984 to train persons from the Cree population of northern Quebec to act as health care advocates and educators, as intermediaries between the Cree population, health services and local organizations, and as participants in assessing health needs. A formative evaluation was initiated which included quantitative analysis of the daily tasks of CHRs and a qualitative component based on documentary research, observation and semi-structured interviews. The evaluation revealed that CHRs actively participated in the ongoing community health programs mainly through health education; the people interviewed showed a high level of satisfaction. However, direct supervision, sufficient continuing education for the CHRs and better integration into health care teams are long term goals which need to be emphasized in the program. PMID- 1884313 TI - Concerning the prevalence of dementia. AB - A recent paper asserted that despite difficulties of measurement, the evidence suggests that the prevalence of dementia may be lower than is generally realized. However, this paper neglected the information provided by other recent studies which show relatively high values for the prevalence of dementia. On the basis of these latter studies and considering non-response, it is here suggested that, in fact, there is no good reason to suspect that the prevalence of dementia is lower than is generally believed. PMID- 1884314 TI - [Major measles epidemic in the region of Quebec despite a 99% vaccine coverage]. AB - The 1989 measles outbreak in the province of Quebec has been largely attributed to an incomplete vaccination coverage. In the Quebec City area (pop. 600,000) 1,363 confirmed cases of measles did occur. A case-control study conducted to evaluate risk factors for measles allowed us to estimate vaccination coverage. It was measured in classes where cases did occur during the outbreak. This population included 8,931 students aged 5 to 19 years old. The 563 cases and a random sample of two controls per case selected in the case's class were kept for analysis. The vaccination coverage among cases was at least 84.5%. Vaccination coverage for the total population was 99.0%. Incomplete vaccination coverage is not a valid explanation for the Quebec City measles outbreak. PMID- 1884315 TI - A review of the epidemiology, public health importance, treatment and control of head lice. AB - Head lice are cosmopolitan and endemic. While they are not responsible for the spread of any disease, they are the cause of considerable social distress. They can infest anybody and do not discriminate between class or cleanliness. Head lice are transmitted primarily by direct contact. The only satisfactory method to clear an infestation is by chemical treatment. The most effective pediculicides to date are those which contain permethrin (Nix) or malathion (Prioderm). Compliance with product instructions eliminates the need for nit removal after treatment. Treatment of inanimate objects and the environment should be discouraged. To obtain effective control of head lice, the whole community needs to be involved. Parents must be encouraged to screen themselves and their children regularly in the home, and to treat themselves only when necessary. PMID- 1884316 TI - Children's respiratory hospitalizations and air pollution. PMID- 1884317 TI - A pilot study to investigate transmission of headlice. PMID- 1884318 TI - The impact of medical care on mortality in Canada, 1959-1988. PMID- 1884319 TI - Cystic fibrosis. Infection, immunopathology, and host response. PMID- 1884320 TI - Allergic bronchopulmonary aspergillosis in patients with cystic fibrosis. PMID- 1884322 TI - Upper respiratory disease, sinusitis, and polyposis. PMID- 1884321 TI - Inflammation in the lung in cystic fibrosis. A vicious cycle that does more harm than good? PMID- 1884323 TI - Airway reactivity in cystic fibrosis. PMID- 1884326 TI - Heart-lung and lung transplantation for cystic fibrosis. AB - End-stage lung disease in Cystic Fibrosis (CF) now is considered to be one of the indications for heart-lung or double lung transplantation. Results of this surgery for 50 or so CF patients in the US and Europe are about the same as for other diseases, although there are some postoperative problems specific for this diagnosis. These include: need for higher oral dosages of cyclosporine, likelihood of precipitation of diabetes mellitus with high dosage corticosteroid therapy for acute lung rejection, constant threat of pathogens remaining in the sinuses, increased likelihood of drug toxicity to the liver and kidneys, and need to make a psychological transition from a patient with a fatal disease to one with optimism about the future. Although improved postoperative management likely will improve postoperative mortality and morbidity, scarcity of donor organs and the high cost of the procedure will limit the impact of this procedure on the general CF population. PMID- 1884325 TI - Drug allergy in cystic fibrosis. PMID- 1884324 TI - Pharmacokinetics of drugs in cystic fibrosis. AB - Considerable work has been conducted on patients with CF to clearly demonstrate enhanced clearances of many, but not all drugs. The precise mechanisms for enhanced drug clearance in CF remain to be elucidated, and it will be important to examine the two major organs of drug elimination, the kidney and liver, for answers to these questions. Although it has not been studied to date, the role of the lung as a contributor to enhanced drug clearance in CF needs to be considered as well. In the liver it appears that both hepatic biotransformation as well as biliary excretion may be enhanced. In the kidney, there is enhanced CL of acidic drugs, but variable findings for cationic and zwitterionic drugs. The latter finding can be explained on the basis of the pKa of the drugs and the urine pH. It would be most appealing if enhanced renal and nonrenal clearance of drugs in CF could be attributed to a common single defect. At this time, there is no obvious candidate, although altered transmembrane transport would represent a place to start. PMID- 1884327 TI - The relationship between atopy and cystic fibrosis. AB - The incidence and clinical significance of allergy in cystic fibrosis have been discussed. There is little evidence that the high prevalence of positive allergy skin tests in CF is a clinical manifestation of a hypersensitivity lung disease complicating the primary pulmonary disorder, except in the special case of allergic bronchopulmonary aspergillosis. The lung disease of CF appears to be caused by excessive bronchial secretions and recurrent infection that are the result of abnormal ion transport across the apical membrane of the respiratory epithelial cell. There are two important questions concerning the allergic reactions: Are they clinically significant, and, why do they occur? The former question is partly resolved by the data presented, although well-controlled studies of intervention would help to resolve it further. The cause of these reactions, which occur particularly in relationship to the mold Aspergillus fumigatus, is unknown but the author is inclined to the view that they are the result of recurrent infection that induces heightened immunologic reactivity to inhaled allergens. The significance of AF may be simply that this mold has a "predilection for diseased airways" or may be more complex; for example, owing to abnormal ion composition in respiratory secretions, abnormal lectin expression by CF respiratory epithelial cells, or selective filtration by the airways based on particle size. PMID- 1884329 TI - Cystic fibrosis. Infection and immunity to Staphylococcus aureus and Haemophilus influenzae. PMID- 1884331 TI - The occupational stress of judges. AB - This paper reports the results of what is believed to be the first systematic survey of the Canadian judiciary about work-related stress. County and District Court judges from four provinces who were attending an educational event on two successive years (N = 104) reported in writing, anonymously, their perceptions of the most stressful aspects of being a judge. A similar survey of their spouses (N = 48) added another perspective to the findings. The overwhelming majority of respondents reported aspects of the work itself (for example, sentencing, child custody cases, judgements, decision-making, and jury trials) as being their primary source of occupational stress. This is not in keeping with the results of most studies, which find that workers view job factors such as role conflict, employer/employee relationships, and career decisions as being more stressful than the actual work they perform. Qualitative material from individual and group interviews suggests that additional preparation and training for the bench and mechanisms for reducing isolation and improving communication might alleviate the stress experienced by judges, while helping them to cope more effectively with their increasingly complex and difficult roles. PMID- 1884328 TI - Cystic fibrosis. Infection and immunity to Pseudomonas. AB - Chronic pulmonary infection with P. aeruginosa in CF may result from: 1. An initial failure of clearance mechanisms (increased adherence) leading to the development of a highly compartmentalized inflammatory reaction; 2. Inhibition of clearing mechanisms for bacteria present in the bronchial lumen; and 3. A largely ineffective, and possibly damaging, hyperactivity of inflammatory cells in the lumen and bronchial wall. The special relationship between the CF host and P. aeruginos, always long-term, and frequently subtle in its complexity, needs further understanding in order to develop new strategies for the treatment of chronic lung infections with this organism. PMID- 1884330 TI - The impact of respiratory viral infections in patients with cystic fibrosis. AB - Respiratory viruses have been implicated in pulmonary exacerbations of CF and in the long-term course of pulmonary dysfunction in these patients. However, the data are by no means complete and there is the clear need for more intensive evaluations of the role of viral pathogens in this population. Further controlled prospective studies assessing the impact of viral infections in large cohorts of patients with CF are still necessary. Placebo-controlled, antiviral treatment protocols also should be initiated. In clinical practice at the present time, patients with CF should be assessed for respiratory viral infections, at least at the time of hospitalizations for pulmonary deterioration. This assessment should include obtaining specimens from the respiratory tract for viral cultures and rapid respiratory viral antigen detection. Identifying a respiratory viral infection may alter clinical care. The patient can be isolated appropriately, and it may be possible to reduce the intensive use of expensive and potentially toxic parenteral antibiotics. The role of antiviral therapy in these patients must await further evaluations. The mechanisms of the short- and long-term effects of respiratory viruses in patients with CF have not been defined. However, pathophysiologic studies conducted in normal children and adults allow the development of several plausible hypotheses. The definition of mechanisms of injury in this population must be a priority, since it may influence clinical practice. If airway obstruction is the principal mechanism of viral-induced injury, therapeutic approaches designed to relieve the obstruction would be most appropriate. For example, if the obstruction resulted from induced or aggravated reactive airway disease, the current common practice of prescribing chronic bronchodilator therapy would be appropriate. This therapy might be especially suited to those experiencing frequent viral infections. In addition, the administration of bronchodilators to patients during acute exacerbations of pulmonary disease caused by viruses might be of clinical benefit. If, on the other hand, the principal mechanism of viral-induced injury is found to be through synergistic interaction with bacteria, the current practice of aggressive antimicrobial therapy would remain appropriate. PMID- 1884332 TI - The prevalence and correlates of behaviour problems in learning disabled children. AB - A retrospective cross sectional study of the prevalence of emotional problems among 502 learning disabled children seen in a specialized learning centre was conducted. Learning disabled children, diagnosed by an experienced clinician, were tested for emotional disturbances using the Child Behavior Checklist. The prevalence of behaviour problems among these children was 43%. This was much higher than the ten percent expected when this measure is used in a general population. There was no greater frequency of behaviour problems in children referred by teachers than in those referred by parents. Results of logistic regression analyses reveal that children who were adolescents, from non intact families, or from lower social class backgrounds had an increased odds of having behaviour problems. The implications of these findings are examined, especially in light of possible methodological problems including selection bias, which may account for the association between emotional problems and learning disabilities found in other studies. PMID- 1884333 TI - Pilot study of anxiety and depression in prepubertal children. AB - Early detection of anxiety and depression is important because of the relationship between these disorders, suicide and other problems (i.e. social, phobias, learning problems). This study screened prepubertal students in a school setting for symptoms of anxiety and depression using self-report measures (Revised Children's Manifest Anxiety Scale and the Children's Depression Inventory). Controls and children who scored high on measures of anxiety or depression or both were interviewed with their parents and were tested using the Diagnostic Interview for Children and Adolescents (computer version) and the Peabody Individual Achievement Test. Initial results indicated that anxiety is more prevalent in prepubertal children than depression. The correlation between different diagnostic measurements used in this project was calculated. A correlation was found between low scores of self-esteem and high scores of anxiety and depression on self-reports. It is concluded that self-report measures are good screening tools. PMID- 1884334 TI - [Judicial aspects of treatment of incompetent psychiatric patients who categorically refuse treatment]. AB - Psychiatrists in particular face a clinical, legal and social dilemma in treating their patients who are likely to categorically oppose treatment. This article illustrates this dilemma in the context of Quebec's Bill 145, resulting in the care of psychiatric patients being increasingly referred to the courts. After presenting this legislation and a case, the authors illustrate the impact of this legislation in light of their own experience and similar legislation in the United States. The mechanisms proposed by Bill 145 have proved costly in several respects as well as cumbersome and ineffective. The authors propose the establishment of an administrative tribunal as an alternative to the current recourse to the courts. PMID- 1884335 TI - Electrical dosage and efficacy in electroconvulsive therapy. AB - The traditional view is that the elicitation of a series of generalized cerebral seizures is the essential requirement for efficacious electroconvulsive therapy (ECT). This theory is the basis of many recent recommendations that the minimum electrical dose required to elicit generalized seizures should be used. Evidence challenging this theory is reviewed, which suggests a role for supra-threshold electrical stimulation in ECT. Hypotheses to explain these findings are examined, and recommendations are made. PMID- 1884336 TI - Deceptions in psychotherapy: case report and considerations. AB - Deliberate deception by a patient in psychotherapy is a deviation from a fundamental requirement of the patient-therapist relationship. When deceptions are discovered or admitted, it is crucial to analyze them for their value in understanding conflicts, transference relationships, and current stresses. These issues are illustrated with a case involving an elaborate deception carried out over several months by a patient in psychotherapy. PMID- 1884337 TI - Using meta-analysis in psychiatric research. AB - Meta-analysis is a technique for summarizing the results of many studies which can allow reviewers in a particular field to arrive at a synthesis of the various findings in a more objective manner than relying on expert opinion and combine the results of these studies to arrive at an overall estimate of the magnitude of the effect of a treatment, to determine if the evidence favours its effectiveness. The technique consists of determining an effect size or odds ratio for each study and combining them, taking into account the fact that studies with large samples should exert more influence than those with small samples. However, the procedure is not mechanical. The reviewer must make a series of decisions regarding the studies to be included or excluded, the weight to place on the methodological rigour of the trials, the results from each study to be used, how to handle differences in the magnitude of the results across studies, how to derive the best overall estimate of the effect across studies, and how to determine the precision of that estimate. Each of these decisions can affect both the quality of the review and the nature of the findings. PMID- 1884338 TI - Psychogenic voice disorders: literature review and case report. AB - This paper explores some of the similarities and differences between hysteria and hypochondriasis and suggests that voice disorders are a prototype of disorders which reflect the intricate interplay of emotional, cognitive and physiological functions. Speech production requires the involvement of various systems of the body, including the central nervous system, respiratory and vocal systems. Voice disorders can take many different forms and can be caused by a variety of factors. A review of the relevant literature is presented along with a clinical case record of a woman with hysterical dysarthria. PMID- 1884339 TI - Sleep disturbance in depression reconsidered. AB - The well documented observation of a characteristic sleep disturbance in depression has been accorded a good deal of significance. Several current hypotheses regarding the etiology of depression, are based on these findings. However, a review of the descriptive studies shows that care has not generally been taken either to restrict or objectively measure daytime sleep. Evidence is presented suggesting that daytime sleep may occur in depressed patients more frequently than commonly thought and that, in normal subjects, daytime napping can result in nocturnal sleep changes similar to those seen in depressed patients. A model is proposed in which the nocturnal sleep disturbance in depression reflects the occurrence, during the daytime, of frank slow wave sleep or periods of large amplitude, slow wave EEG activity as a consequence of a dampening of the circadian rhythm of sleep propensity. PMID- 1884340 TI - Assessment of premenstrual complaint using the Premenstrual Assessment Form: comparison of two populations. AB - The Premenstrual Assessment Form (PAF) provides frequencies of diagnoses for subjects meeting the criteria for typological classifications which are similar in New York and Edmonton, suggesting that the instrument is stable in assessing premenstrual complaint. However, the frequency with which an unselected population meet the criteria suggests that more strict criteria and/or a "severity index" would be appropriate. It seems likely that a modified form of the PAF could fulfil some of the intentions of its originators. PMID- 1884341 TI - Fluoxetine in panic disorder. AB - This paper presents the cases of two patients who suffered from panic disorder with agoraphobia and depression. One had been refractory to alprazolam and tricyclics and to behaviour therapy; she had responded to phenelzine, but due to a weight gain of 50 lbs, had discontinued treatment and she relapsed. The second patient, who also suffered from post-traumatic stress disorder, did not respond to alprazolam, imipramine or to phenelzine, but gained weight (33 lbs) on phenelzine. Both patients responded to fluoxetine 80 mg per day without concomitant weight gain. PMID- 1884342 TI - Pattern of substance abuse in psychiatric inpatients. AB - This study examined the pattern of substance abuse in a sample of 114 psychiatric inpatients using a standardized diagnostic interview. As predicted, psychiatric inpatients reported a significantly higher rate of substance abuse than a randomly selected community sample. Approximately three-quarters of the inpatients abused at least one substance. Almost one-half of the patient sample reported abusing more than one substance. These findings emphasize the need to screen psychiatric inpatients for substance abuse using a standardized diagnostic instrument and to develop treatment programs for substance abuse in psychiatric patients. PMID- 1884343 TI - The dangerousness criterion for civil commitment. PMID- 1884344 TI - Hallucinations controlled with anticonvulsants. PMID- 1884345 TI - Flushing reaction associated with the interaction of phenelzine and clonazepam. PMID- 1884346 TI - Late onset (hypo)mania. PMID- 1884347 TI - Cytogenetic heterogeneity of genetically marked and metastatically competent "dominant" tumor cell clones. AB - Examination of tumors usually shows them to consist of phenotypically and clonally heterogeneous cell subpopulations. On the other hand, previous studies from our laboratory have provided compelling evidence for the rapid evolution, or overgrowth, of single "dominant" clones during the course of primary tumor growth. Thus in one such study, syngeneic CBA mice were injected with a mixture of 50-100 different genetically tagged clones of a mouse mammary carcinoma called SP1. The vast majority of these clones were non-metastatic. The different clones were tagged by random integrations of foreign DNA using calcium phosphate mediated transfection of the plasmid pSV2neo, the resultant primary tumors were found to consist of a single dominant clone, called B5, which was also shown to be metastatically competent. The detection of single dominant clones such as B5 in primary tumors can be reconciled with the concept of tumor cell heterogeneity if it could be shown that the dominant clone was in fact heterogeneous for other genetic or phenotypic markers, i.e., was homogeneous only for the plasmid-based genetic marker used for its detection. To study this question, we examined the karyotypes of several sublines of B5, two derived from a primary advanced tumor and one from a spontaneous lung metastasis. We indeed found evidence to support the existence of marked cellular heterogeneity within and between the three sublines examined. Thus, while all three retained common cytogenetic markers, each also expressed unique markers. Moreover, karyotypic heterogeneity within a given subline was observed. Thus the concept of clonal dominance of primary tumors by metastatically competent cell subpopulations is not incompatible with the concept of the cellular heterogeneity of tumors. The implications of the results are discussed. PMID- 1884348 TI - Unusual translocations and other changes in acute leukemia. AB - We report three cases of ANLL and one case of ALL in which we found chromosome abnormalities not previously described. The first patient had a (9;11;16)(p22;q23;p13) translocation in the relapse after bone marrow transplantation. In the second case, a secondary leukemia following a Wilms' tumor, there was a single chromosome anomaly, an inversion of chromosome 13. The third case also presented an isochromosome 13q. In the fourth patient we observed a translocation between two achrocentric chromosomes, as in the third patient, but not of the Robertsonian type: t(21;21)(q22.1;q22.5). PMID- 1884349 TI - Clonal chromosomal abnormalities in hemangiopericytoma. AB - We report the cytogenetic findings in nine hemangiopericytomas studied after short-term culture. Clonal chromosome abnormalities were present in four cases. One case had a simple translocation (12;19)(q13;q13.3) as the sole abnormality whereas complex and multiple chromosomal abnormalities involving almost all chromosomes in the complement characterized tumors from the three other cases. PMID- 1884350 TI - Mediastinal germ cell tumor with secondary nongerm cell malignancy, and extensive hematopoietic activity. Pathology, DNA-ploidy, and karyotyping. AB - We report on a malignant germ cell tumor located in the anterior mediastinum. After chemotherapy the tumor was classified as residual teratoma with sarcomatous components. There was extensive hematopoiesis in the tumor tissue. The tumor cells had a modal chromosome number of 76; the only structural abnormality was a deletion of the long arm of chromosome 9. An i(12p) chromosome was lacking in this tumor. Karyotyping of peripheral blood and bone marrow occasionally showed metaphases with numerical and structural abnormalities, probably related to chemotherapy. The patient died within two years after the initial diagnosis, of a poorly differentiated hematopoietic malignancy, probably of myelomonocytic origin, based on morphology and the fact that non-specific esterase activity was demonstrated in the tumor cells. The karyotype of this malignancy was highly abnormal, but unrelated to that of the mediastinal malignant GCT. In this case there is no proof that the secondary malignancy was derived from the primary mediastinal malignant GCT. In view of the multiple aneuploid stem lines in the primary tumor, this possibility cannot be dismissed either. PMID- 1884351 TI - Hemizygous deletion of the 3' end of the RB1 gene in a case of Philadelphia positive-acute lymphoblastic leukemia. AB - In order to address a possible role for the human retinoblastoma susceptibility (RB1) gene in hematopoietic malignancies, 34 cases of different types of leukemia without chromosomal abnormalities at band 13q14 were analyzed by Southern blot hybridization. A large deletion encompassing exon 18-27 was detected in one case of Ph1 positive-acute lymphoblastic leukemia. Interestingly, this deletion appeared to be similar to another deletion recently reported in a leukemic cell line derived from a T-ALL. No rearrangement was detected in all other leukemias. PMID- 1884352 TI - Differential evolution in chromosomal composition during multiple cycles of subcutaneous and intravenous metastasis. AB - It has been proven that multiple cycles of metastasis can improve the metastatic potential and homing specificity of a tumor cell population. In the present study, verification of genetic alterations during changes in metastatic behavior was done by analyzing the chromosome composition of a methylcholanthrene induced murine fibrosarcoma, 3AM during multiple cycles of subcutaneous (SC) and intravenous (IV) metastasis. After 10 cycles of SC metastasis, a cell type, 7B, with a small t(19;19)(A;A) metacentric marker chromosome was enriched from 4% in the original population to 90% in FIOR. However, when the tumor cells were injected IV rather than SC, no enrichment of the 7B cell type was observed. Instead, a cell type AX with a large t(14;19)(E5;A) acrocentric marker chromosome was enriched from 1% in the parental population to 76% in F1OIV after 10 cycles of IV metastasis. The polyploid dominant FIOIV was found to be extremely high in IV metastasis (411 foci/lung) but low in SC metastasis (48 foci/lung). The diploid dominant FIOR appears to be high in both SC (163 foci/lung) and IV (301 foci/lung) metastasis. The data obtained suggest that metastasis will lead to the selection of specific preexisting cell types, and the type of cell selected will depend on the route of metastasis. Furthermore, during metastasis, new cell types may also be produced de novo through chromosomal structural and numerical aberrations. PMID- 1884353 TI - Chromosomal aberrations in follicular thyroid carcinoma. Case report of a primary tumor and its metastasis. AB - We present the result of a cytogenetic study of a case of follicular carcinoma of the thyroid and its metastasis. Both tumors have a low number of chromosomes. The primary tumor is characterized by a idic(22;22)(p11;p11). The skeletal metastasis has also structural abnormalities of chromosome 22. PMID- 1884354 TI - Leiomyoma cells with 12q15 aberrations can be transformed in vitro and show a relatively stable karyotype during precrisis period. AB - Tumor cells from three uterine leiomyomas showing translocations involving 12q14 15 were transformed by transfection using the "early regions" of the SV40 genome. The cells had a higher proliferative capacity, were able to form colonies in soft agar, and showed an increased growth potential. Karyotype analyses of these transformed leiomyoma cells showed that the cells had retained the initial t(12;14) and t(12;15). PMID- 1884355 TI - Complex chromosomal abnormalities in a patient with refractory anemia with excess blasts (RAEB). AB - We report a new case of refractory anemia with excess blasts (RAEB) having complex chromosomal abnormalities. The 5q- associated with RAEB and other preleukemic syndromes was present in 100% of the cells; however, 60% of the cells had a highly unusual derivative chromosome involving the short arm of chromosome 1 and the long arm of chromosome 5, i.e., t(1;5)(p36;q14). Although the patient presented with highly complex chromosomal abnormalities, his initial clinical presentation was that of typical refractory anemia with excess blasts. Shortly after diagnosis (7 months), the patient developed acute leukemia. PMID- 1884356 TI - Isodicentric chromosome 18q as sole abnormality in a histologically normal bone marrow from a patient with diffuse large-cell non-Hodgkin's lymphoma. AB - Cytogenetic analysis was performed on the histologically and immunophenotypically normal bone marrow (BM) of a 33-year-old woman with non-Hodgkin's lymphoma (NHL) before BM harvest. Unstimulated 24- and 48-hour cultures produced only normal metaphases. A pokeweed mitogen (PWM)-stimulated 48-hour culture, however, showed a clonal isodicentric chromosome 18q as the sole abnormality, suggesting a role for this approach in detection of submicroscopic BM involvement by B-cell NHL. PMID- 1884357 TI - Nonrandom t(1;22)(p12-p13;q13) in acute megakaryocytic malignant proliferation. AB - A case of acute megakaryocytic leukemia (M7) and one of acute myeloid hemopathy affecting megakaryocytic and erythrocytic cell lineages in infants are reported. Both patients had t(1;22)(p12-p13;q13). This translocation was previously observed in a congenital M7 leukemia. These studies suggest that t(1;22) translocation can be nonrandom in M7. PMID- 1884358 TI - The telomere in cancer. All's not well that doesn't end well. PMID- 1884359 TI - Molecular differentiation of two different translocations producing two apparent Ph chromosomes in a patient with CML. AB - A case of chronic myelogenous leukemia (CML) is described whose leukemic cells appeared to contain two Philadelphia (Ph) chromosomes originating from different translocations involving the two chromosomes 22. The karyotype of the affected cells, established on two different occasions, was: 46,XY,t(9;22)(q34;q11),t(15;22)(p11;q11) with no normal chromosomes 22 and only one 9q+ in each of 115 marrow cells examined. The same findings were present in 50 peripheral blood cells cultured without phytohemagglutinin (PHA) stimulation. When stimulated with PHA, a normal male karyotype was present in the 11 cells examined. There were no additional chromosomal abnormalities and no indication of a blastic crisis after nearly 1 year following the original study. Analysis of the breakpoint cluster region (bcr) on chromosome 22 in the DNA of the affected cells (marrow) revealed evidence for one rearranged chromosome 22 and one normal chromosome 22, indicating that the t(15;22) was not due to the usual Ph translocation seen in CML. The results point to the crucial usefulness of molecular analysis in confirming cytogenetic results related to Ph translocations in CML. PMID- 1884361 TI - Involvement of chromosome 5 in large bowel cancer. AB - We present here 3 of 30 cases of large bowel cancer cytogenetically studied, with deletion of chromosome 5. One of them presented a terminal deletion and the other two an interstitial deletion of chromosome 5q. In all three cases the segment 5q12-22 was deleted. Our findings may show that the segment 5q12-22 is important for a subgroup of colorectal cancers. PMID- 1884360 TI - Age-dependent prognostic significance of N-myc amplification in neuroblastoma. The Italian experience. PMID- 1884362 TI - Nonmitotic mechanism for recessive expression of retinoblastoma in constitutional 13q14 deletions. PMID- 1884364 TI - An identical chromosome abnormality: der(6)t(6;7)(q13;p13) in two patients with peripheral T-cell lymphoma. PMID- 1884363 TI - Chromosomal localization of the APL t(15;17) breakpoints by molecular cytogenetic analysis. PMID- 1884365 TI - Cluster of trisomy 12 to tumors of the female genitourinary tract. PMID- 1884366 TI - Karyotypes in acute childhood leukemias may lose prognostic significance with more intensive and specific chemotherapy. PMID- 1884367 TI - Effect of oxygenation, pH and hyperthermia on RSU-1069 in vitro and in vivo with radiation in the FSaIIC murine fibrosarcoma. AB - We have evaluated the combination of the radiosensitizing and bioreductive alkylating agent RSU-1069 with hyperthermia and radiation in an attempt to improve the potential effectiveness of hyperthermia and radiation against locally advanced malignancies. In vitro studies in FSaIIC murine fibrosarcoma cells demonstrated that 1 h exposure to RSU-1069 was more cytotoxic toward hypoxic than normally oxygenated cells at 37 degrees C and pH 7.40 and was only minimally more cytotoxic at hyperthermic temperatures. At pH 6.45, however, RSU-1069 became significantly more toxic toward hypoxic cells and its cytotoxicity was markedly increased at hyperthermic temperatures. In contrast, the ability of this agent to radiosensitize hypoxic FSaIIC cells significantly diminished at pH 6.45. Hoechst 33342 diffusion selected FSaIIC tumor subpopulation studies revealed that hyperthermia and RSU-1069 were more toxic towards dim (hypoxic) cells, while radiation was more toxic towards bright (normally oxygenated) cells. A combination of all three modalities resulted in an equal and significant kill of hypoxic and oxygenated cells. These results suggest that the combination of RSU 1069, local hyperthermia and radiation has considerable clinical potential. PMID- 1884368 TI - On the tumorigenicity of mitochondrial DNA-depleted avian cells. AB - We have examined the tumorigenic potential of mitochondrial DNA-depleted (mtDNA-) cells derived from the tumorigenic chicken cell line DU24. The mtDNA- cells were unable to proliferate in the wing web of day-old chicks. Cytoplasmic hybrids resulting from crosses between the mtDNA- whole cells and cytoplasts from enucleated parental cells (mtDNA+) recover both mtDNA and tumorigenicity. These results are in accordance with those obtained in prior experiments where mtDNA was shown to modulate the anchorage-independent phenotype of transformed avian cells. PMID- 1884369 TI - Preclinical evaluation of a positron emitting progestin ([18F]fluoro-16 alpha methyl-19-norprogesterone) for imaging progesterone receptor positive tumours with positron emission tomography. AB - Three 21-fluoro-progestins were investigated as potential imaging agents for the in vivo assessment of human progesterone receptor positive neoplasms with positron emission tomography. In competitive binding assays these compounds demonstrated high specificity, competing only for progesterone receptors. Binding to other steroid receptor types was negligible. Based on its high affinity binding, 21-fluoro-16 alpha-methyl-19-norprogesterone was selected for further evaluation in vivo. Tissue distribution studies in immature estrogen primed female rats revealed high uterine uptake of 21-[18F]fluoro-16 alpha-methyl-19 norprogesterone ([18F]FMNP). At 60 min after injection the ratio of uptake of radioactivity by uterine tissue to that of blood was 7. This ratio increased to 24 at 180 min. A selective decrease in uterine uptake was observed after administration of [18F]FMNP with excess unlabelled progestin. Rats bearing hormone responsive MT-W9A mammary adenocarcinomas were used to examine [18F]FMNP for tumour uptake. Animals were used irrespective of the phase of the estrous cycle. At 180 min the uterus to blood ratio and the tumour to blood ratio ranged from 3 to 20 and 3 to 17, respectively. Uterine and tumour tissue was assayed for cytosolic estrogen and progesterone receptors using a dextran-coated charcoal method and Scatchard plot analysis. The results indicate that the in vivo uptake of [18F]FMNP by uterine and mammary tumour tissue correlates well with the progesterone receptor concentration (rs = 0.98 and rs = 0.88, respectively). It is concluded that the uptake of [18F]FMNP by progesterone receptor positive tissue in vivo is primarily receptor related and that this uptake is attributable to the progesterone receptor. The study demonstrates the potential applicability of [18F]FMNP and positron emission tomography for imaging progesterone receptor positive neoplasms. PMID- 1884370 TI - Lectin reactivity of murine fibrosarcoma lines with a different metastatic potential. AB - Lectins are suitable tools for investigating the glycoconjugate characteristics of metastatic cells. In the present study, we investigated whether there were differences between high metastatic T3 cells and a low metastatic isolate in their reactivities to several lectins specific for galactosyl and sialyl groups. Analysis of reactivity of the two cell lines to wheat germ agglutinin revealed a complex pattern. In fact, T3 cells had high-affinity, neuraminidase-resistant as well as low-affinity, neuraminidase-sensitive receptors. Instead, the low metastatic isolate showed only high-affinity receptors, both neuraminidase resistant and neuraminidase-sensitive The two cell lines reacted similarly to galactose-specific lectins. These findings indicate that sialyl groups, rather than galactosyl groups, affect the metastatic behavior of our cell system. PMID- 1884371 TI - Activating mutations at codon 61 of the c-Ha-ras gene in thin-tissue sections of tumors induced by aristolochic acid in rats and mice. AB - The plant extract aristolochic acid, which consists mainly of aristolochic acid I (AAI) and aristolochic acid II (AAII), induces tumors in rats and mice. Thin tissue sections of rat tumors induced by AAI and of mouse tumors induced by aristolochic acid, were analyzed for c-Ha-ras mutations in codon 61. Areas of neoplastic and histologically normal tissue were manually scraped out and separated. Using the polymerase chain reaction (PCR) and mutation detection by selective oligonucleotide hybridization, we observed AT----TA transversion mutations in DNA of neoplastic portions, but not in DNA of adjacent normal tissue in both rat and mouse tumors. PMID- 1884372 TI - Monoclonal antibody CM-H-9 detects circulating placental isoferritin in the serum of patients with visceral metastases of breast cancer. AB - The aim of the current pilot study was to determine whether placental isoferritin (PLF) can be detected in the serum of patients with metastatic breast cancer. Sera were obtained from breast cancer patients with metastatic disease (n = 100), from breast cancer with no evidence of disease (n = 70) and from healthy female controls (n = 34). PLF and total serum ferritin levels were independently measured using specific monoclonal antibody ELISAs in a double-blind study. It was found that the mean serum PLF levels were significantly elevated only in patients with visceral metastases (lung, liver, brain) compared with the levels of patients with non-visceral metastases (bone, skin) or with healthy controls. Contrary to this, analysis of total serum ferritin levels did not reveal significant differences between these groups. Considering 0-10 units/ml as a PLF negative result, it was found that PLF was negative in 87.5% of healthy controls and in 96% of breast cancer patients with no evidence of disease. In contrast, PLF was positive in 73% of the patients with visceral metastases and in 29.7% of those with non-visceral metastases. The striking difference between visceral and non-visceral metastases is not yet understood. It could result from a difference in the degree of vascularisation or, alternatively, a difference in the cell types and genes expressed by cells metastasizing to visceral or non-visceral organs. PMID- 1884373 TI - Comparative metabolism and urinary excretion of N-mononitrosopiperazine and N,N' dinitrosopiperazine in the rat. AB - The metabolism of N-mononitrosopiperazine (NPz) and N,N'-dinitrosopiperazine (DNPz) was investigated in Sprague-Dawley rats. When an oral dose of 50 micrograms/rat NPz was administered, 10.5% of the dose was recovered unchanged in urine together with N-nitroso-3-hydroxypyrrolidine (NHPYR, 1.3% of administered NPz dose) and N-nitrosodiethanolamine (NDELA, 0.3%). For DNPz, 7.7% of the administered dose together with NPz (0.04%), NHPYR (2.9%), NDELA (6.7%) and N nitroso(2-hydroxyethyl)glycine (NHEG, 20.2%) was recovered in urine after 24 h. These results show extensive metabolism of both NPz and DNPz and suggest that both NPz and NHPYR could be analysed in urine as markers for the endogenous nitrosation of piperazine in patients receiving antihelminthic treatment with piperazine. PMID- 1884374 TI - Oncogene expression and prognosis in cervical cancer. AB - Cancer of the uterine cervix accounts for 80-85% of all female genital tract malignancies in India and also remains a major problem for oncologists in other parts of the world. A major concern regarding the disease is the lack of specific tumor markers for early detection, for accurate prediction of biological behaviour and for accurate assessment of prognosis. A new and exciting answer to this issue may now be available with the description of specific oncogenes and oncoproteins associated with this malignancy. On a clinical level these genes and their products may allow us to improve our understanding of disease etiology, and provide more precise diagnostic, prognostic and therapeutic characterization of individual tumors. This paper discusses the possibilities of using altered expression of oncogenes and their products in neoplastic tissue as markers for the diagnosis and prognosis of cervical cancer. These data support the view that detailed analysis of such gene expression has the potential to predict tumor behavior. PMID- 1884375 TI - Involvement of lauric acid hydroxylase in the activation of beta-substituted nitrosamines. AB - The mutagenicity of N-nitrosobis (2-hydroxypropyl) amine (BHP), N-nitrosobis(2 oxopropyl)amine (BOP) and N-nitroso-(2-hydroxy-propyl) (2-oxopropyl) amine (HPOP) was measured in V79 cells. Hepatocytes, used to metabolize (activate) the nitrosamines, were isolated from untreated Syrian hamsters (control) and hamsters treated with clofibrate (CLO) or dehydroepiandrosterone (DHEA) in vivo. BHP and HPOP mutagenicity increased 3- and 2-fold when hepatocytes from CLO- and DHEA treated hamsters were used. BOP mutagenicity did not increase. 10-Undecynoic acid, a lauric acid hydroxylase inhibitor, inhibited the increase in BHP and HPOP mutagenicity by 80-90% but did not affect that of BOP. Antimycin A1, a fatty acyl coenzyme A beta-oxidase inhibitor did not affect the mutagenicity of these nitrosamines. Lauric acid hydroxylase, probably omega-1 hydroxylase (cytochrome P 450 IVA2), appears to be involved in the activation of BHP and HPOP. PMID- 1884376 TI - Enhanced immunoreactivity of ras oncogene p21 protein in urinary bladder epithelium of rats treated with N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide. AB - Normal urothelium and various lesions of the rat urinary bladder induced by the dietary administration of 0.2% N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT) (up to 77 weeks) or by the combination of 0.2% FANFT and the subsequent administration of 5% sodium saccharin or 2% DL-tryptophan (up to 104 weeks) were evaluated for immunoreactivity with monoclonal antibody to ras p21 by avidin biotin immunohistochemistry. Seventy-one to 100% of transitional cell carcinomas showed strong reactivity to the antibody to ras p21 depending on treatment with long-term administration of FANFT or by 6 weeks administration of FANFT followed by sodium saccharin or DL-tryptophan. Focal reactivity to the ras p21 antibody was frequently observed in the hyperplastic (57-96%) or normal appearing urinary bladder epithelium (50-100%) in rats treated with FANFT (FANFT alone or in combination with sodium saccharin or tryptophan) but not in hyperplasia or normal epithelium in rats given sodium saccharin or tryptophan alone, without pretreatment with FANFT or in untreated controls. The present results show that there is a close association of enhanced immunoreactivity with ras p21 antibody in the urinary bladder epithelium to FANFT treatment, and that ras p21 is expressed in normal, hyperplastic and neoplastic lesions of the bladder of rats treated with FANFT. These results suggest that enhanced immunoreactivity with ras p21 is observed as a consequence of the treatment with FANFT but it alone does not reflect the progression from benign to malignant lesions. PMID- 1884378 TI - Discoveries and opportunities in cancer research: a celebration of the 50th anniversary of the journal Cancer Research. Presented at the 82nd annual meeting of the American Association for Cancer Research. Houston, Texas, May 15, 1991. Proceedings. PMID- 1884377 TI - A brief overview of the journal Cancer Research. An introduction to the symposium, "Discoveries and Opportunities in Cancer Research: A Celebration of the 50th Anniversary of the Journal Cancer Research". PMID- 1884379 TI - Chemical and physical carcinogenesis: advances and perspectives for the 1990s. AB - Carcinogenesis is a multistage process driven by carcinogen-induced genetic and epigenetic damage in susceptible cells that gain a selective growth advantage and undergo clonal expansion as the result of activation of protooncogenes and/or inactivation of tumor suppressor genes. Therefore, the mutational spectra of chemical and physical carcinogens in these critical genes are of interest to define endogenous and exogenous mutational mechanisms. The p53 tumor suppressor gene is ideally suited for analysis of the mutational spectrum. Such an analysis has revealed evidence for both exogenous and endogenous molecular mechanisms of carcinogenesis. For example, an informative p53 mutational spectrum of frequent G ---T transversions in codon 249 is found in hepatocellular carcinomas from either Qidong, People's Republic of China, or southern Africa. This observation links exposure to aflatoxin B1, a known cancer risk factor in these geographic regions, with a specific mutation in a cancer-related gene. Other studies indicate that abnormalities in genes controlling the cell cycle may cause genomic instability and increase the probability of neoplastic transformation. Finally, mechanistic understanding of carcinogenesis is leading to improved cancer risk assessment and to the identification of individuals at high cancer risk. PMID- 1884380 TI - Cancer dormancy: studies of the murine BCL1 lymphoma. AB - Dormancy in the murine BCL1 lymphoma can be induced by several strategies including cytoreductive therapy of mice with large tumor burdens and challenge of allogeneic chimeric mice or idiotype-immunized mice with BCL1 tumor. Dormant tumor cells were isolated from the spleens of the chimeric mice and the majority were shown to be noncycling. In idiotype-immunized mice that had lost dormancy, tumor growth occurred at a relatively rapid rate. A proportion of idiotype immunized mice that had lost dormancy spontaneously regressed and then again relapsed; in these mice, the serum antiidiotypic levels were inversely related to the tumor burden. PMID- 1884381 TI - Tumor invasion and metastasis: an imbalance of positive and negative regulation. AB - A group of coordinated cellular processes, not just one gene product, is responsible for invasion and metastasis, the most life-threatening aspect of cancer. It is now recognized that negative factors may be just as important as positive elements. Genetic changes causing an imbalance of growth regulation lead to uncontrolled proliferation necessary for both primary tumor and metastasis expansion. However, unrestrained growth does not, by itself, cause invasion and metastasis. This phenotype may require additional genetic changes. Thus, tumorigenicity and metastatic potential have both overlapping and separate features. Invasion and metastasis can be facilitated by proteins which stimulate tumor cell attachment to host cellular or extracellular matrix determinants, tumor cell proteolysis of host barriers, such as the basement membrane, tumor cell locomotion, and tumor cell colony formation in the target organ for metastasis. Facilitory proteins may act at many levels both intracellularly or extracellularly but are counterbalanced by factors which can block their production, regulation, or action. A common theme has emerged. In addition to loss of growth control, an imbalanced regulation of motility and proteolysis appears to be required for invasion and metastasis. PMID- 1884382 TI - Radiation oncology: past achievements and ongoing controversies. AB - With the development of megavoltage treatment and computerized treatment planning the quality and precision of radiation oncology has steadily improved. Likewise, these developments have contributed to better local control for some cancers; however, micrometastatic lesions beyond the radiation treatment field and ineffective systemic treatments for many malignancies hamper efforts at the most important oncological end point, survival. Major advances in cancer therapy are therefore likely to come with improved combined modality treatment representing integration of local modalities with the systemic. These advances, in our opinion, will come from biological developments that address the problems that the modern oncologist faces at the cellular level. The biological developments will incorporate modern molecular biology, continued probing for biochemical mechanisms, and an intensified effort to learn more about the complexities of human tumor physiology. PMID- 1884383 TI - Immunotherapy and gene therapy of cancer. AB - In the past decade, immunotherapies have been developed that are capable of causing prolonged cancer regressions in selected patients with advanced metastatic disease. In the past year, attempts at the gene therapy of cancer have begun. These experimental cancer treatments deserve vigorous exploration. PMID- 1884384 TI - Cancer prevention: recent progress and future opportunities. AB - Knowledge gathered during the past few decades from the fields of cancer epidemiology, carcinogenesis, biochemistry, and molecular biology, much of which was communicated through the pages of the journal Cancer Research, provides powerful new strategies for cancer prevention. Indeed, I believe that it is possible to draft a blueprint for a comprehensive approach to cancer prevention, to be used as we approach the 21st century. This plan includes: (a) expanded epidemiological and laboratory studies to identify the specific causes of human cancers; (b) intervention studies, such as risk reduction by the cessation of cigarette smoking, dietary modifications, chemoprevention, and the development of vaccines for viral agents implicated in human cancer (i.e., hepatitis B, human papilloma virus, Epstein-Barr virus, and certain retroviruses), and (c) early detection and screening. Concepts and methods that have developed in the field of cellular and molecular biology will accelerate this progress. Indeed, we are currently in a very exciting phase of cancer research that brings together fields of cancer research which in the past were often disparate and disconnected, i.e., basic laboratory studies, epidemiology, prevention, and treatment. Thus, the astounding advances in our understanding of the molecular biology of cancer provide a unified concept of the nature of the cancer cell and also suggest new clinical approaches to cancer etiology, prevention, and treatment. Many of the biomarkers being developed for etiological studies, using the approach of molecular epidemiology, can also serve as biomarkers or intermediate end points to evaluate the efficacy of dietary intervention and chemoprevention studies. Some of these biomarkers will also be useful for evaluating the efficacy of cancer therapy. Furthermore, certain compounds being developed for cancer chemoprevention, e.g., the retinoids, may also be useful in the therapy of fully established neoplasms. It seems likely, therefore, that even before the year 2000 these powerful and unifying themes will accelerate advances in both cancer prevention and treatment, thus leading to major reductions in both the incidence and mortality of human cancer. PMID- 1884385 TI - Comparison of selective arginine vasopressin V1 and V2 receptor antagonists on burn shock in the rat. AB - STUDY OBJECTIVE: Two selective V1 and V2 receptor antagonists of arginine vasopressin, d(CH2)5Tyr(Me)AVP and d(CH2)5[D-Ile2, Ile4, Ala9-NH2]AVP, were given intravenously in burn shocked rats to investigate the respective effects of V1 and V2 receptor blockade on the haemodynamic variables in burn shock. DESIGN: Computer assisted on line real time measurements of mean arterial blood pressure, diastolic blood pressure, left ventricular systolic pressure, dP/dtmax, and heart rate were used to study the effects of the receptor antagonists during burn shock. In addition, the radioactive microsphere method was used to measure the changes of cardiac output and regional blood flows to heart, kidney, and liver in response to the antagonists during burn shock. Third degree burns extending over 30% of body surface area were made by dipping the rat's shaved back into water at 100 degrees C for 20 s. EXPERIMENTAL MATERIAL: Male Sprague-Dawley rats (250-300 g) were used in groups of 6-9 per experiment. MEASUREMENTS AND MAIN RESULTS: Mean and diastolic arterial blood pressures, left ventricular systolic pressure, dP/dtmax and heart rate were measured for 8 h after burns. Cardiac output and regional blood flow were measured at 3 h and 8 h postburn. Results showed that blockade of V1 receptor lowered mean and diastolic arterial blood pressures throughout the 8 h period, and raised left ventricular systolic pressure and dP/dtmax only during the early phase of shock. Cardiac output and blood flows to heart, kidney, and liver were increased by the V1 antagonist at 3 h but not at 8 h postburn. The V2 receptor antagonist increased mean and diastolic arterial blood pressures, left ventricular systolic pressure, and dP/dtmax both during the early and during the late phases of burn shock. It also improved cardiac output and blood flows to the heart, kidney, and liver during the early and late phases of burn shock. However, heart rate was not affected by V1 and V2 receptor antagonists. CONCLUSIONS: The V2 like receptor may be the dominating receptor mediating vasopressin's inhibitory effect on the heart. V1 receptor mediated coronary vasoconstriction contributes to the myocardial depression possibly only at the compensatory phase of shock. In addition V1 receptor mediated vasoconstriction is important in maintaining blood pressure during burn shock. PMID- 1884386 TI - Effect of nisoldipine on atherosclerosis in the cholesterol fed rabbit: endothelium dependent relaxation and aortic cholesterol content. AB - STUDY OBJECTIVE: The aim was to determine the effect of the calcium channel blocker nisoldipine on the loss of endothelium dependent relaxation and the accumulation of cholesterol in the aorta produced by feeding a diet enriched with cholesterol. DESIGN: 12 week old New Zealand white rabbits were assigned randomly to four groups with the following dietary and drug regimens: group A--standard diet + 2.5% cholesterol (n = 45); group B--standard diet + nisoldipine (n = 9); group C--standard diet + nisoldipine + 2.5% cholesterol (n = 9); group D- standard diet (n = 9). After 3 weeks the cholesterol supplements were stopped and all animals were given the standard rabbit diet. The animals in groups B and C were given nisoldipine (1 mg.kg-1.d-1) by mouth for the entire 7 week period. EXPERIMENTAL MATERIAL: Aortic tissue was removed for measurement of cholesterol content, endothelium dependent relaxation to acetylcholine, contractile responses to noradrenaline, relaxant responses to sodium nitrite, and sudan staining. Serum was obtained for measurement of cholesterol and triglyceride concentration. MEASUREMENTS AND MAIN RESULTS: At 7 weeks, endothelium dependent relaxation to acetylcholine was impaired in group A compared to group D, while that in group C was not. Aortic tissue cholesterol content in group A was significantly greater than in groups B, C, and D. At 15 weeks, ie, 12 weeks after reversal of the diet, endothelium dependent relaxation had recovered in the animals in group A. There was a significant reduction in the aortic cholesterol content at this stage. In two subgroups of A (groups A2 and A4) which were given nisoldipine immediately after and 4 weeks after cessation of cholesterol feeding respectively, the drug was found to have no influence upon restoration of endothelium dependent relaxation. However, the drug appeared to promote the retention of cholesterol within the aorta after cessation of cholesterol feeding. CONCLUSIONS: Nisoldipine protects against the accumulation of cholesterol and loss of endothelium dependent relaxation in the aorta of rabbits fed a diet supplemented with 2.5% cholesterol for three weeks. Administration of the drug after the lesions are established in the aorta also appears to retard the removal of cholesterol from the aorta. PMID- 1884387 TI - Non-uniform and non-linear end systolic pressure-length relations at low left ventricular pressures in anaesthetised cats. AB - STUDY OBJECTIVE: The aims were (1) to establish a basis for measurements of regional inotropy using the slope (E) of the linear part of the end systolic pressure-length relation; (2) to investigate the range of end systolic pressure where linearity is valid, and particularly its lower pressure limit, called turning point pressure; (3) to determine whether local myocardial inotropy measured by normalised slope, E(n), varies with segment orientation DESIGN: Pressure and two cross oriented segment lengths were measured in the left ventricle. One pair of crystals measured a longitudinal segment, aligned with anterior midwall fibre direction; another pair measured a transverse segment, aligned with endocardial and epicardial fibre direction. Temporary obstruction of the inferior caval vein and descending aorta were performed to produce a wide pressure range of end systolic pressure-length relations during basal as well as high inotropic states (isoprenaline). SUBJECTS: Seven open chest cats anaesthetised with sodium pentobarbitone and nitrous oxide were used. MEASUREMENTS AND MAIN RESULTS - Turning point pressure for longitudinal segments showed lower values than for transverse segments (p less than 0.05). With isoprenaline, turning point pressure increased for all transverse segments, at 103(SEM 8) v 153(19) mm Hg (p less than 0.05), whereas no change occurred for longitudinal segments, at 82(4) v 87(7) mm Hg. In the basal state, E(n) showed lower values in all longitudinal segments compared to transverse segments, except for one pair. E(n) of all segments increased during isoprenaline infusion, except in one segment where no change occurred. CONCLUSIONS - There is a lower limit for linearity of end systolic pressure-length relations; this is affected by segment orientation as well as by the inotropic state of the heart. E(n) as a measure of regional inotropy varies with segment orientation, but offers a local measure of changes in inotropic state. PMID- 1884388 TI - Slow recovery of conduction velocity from use dependent inhibition induced by quinidine in guinea pig ventricular myocardium. AB - STUDY OBJECTIVE: The aim was to investigate whether the use dependent effects of antiarrhythmic drugs on the Na+ current could be applied to explain their effects on impulse conduction. DESIGN: Trains of rapid stimuli were applied to guinea pig papillary muscles via an electrode in the presence of quinidine (20 and 60 mumol.litre-1), and the conduction velocity was determined from the time difference between two signals of the maximal rate of rise (dV/dtmax) of the action potentials at two separate sites. The relationship of the time constants of the onset and recovery from the use dependent inhibition induced by quinidine was determined for the dV/dtmax and the conduction velocity. EXPERIMENTAL MATERIAL: Six male Hartley guinea pigs weighing 200 to 300 g were killed by a blow to the head and the papillary muscles were rapidly excised from the right ventricles. The preparations were superfused with Tyrode solution. MEASUREMENTS AND MAIN RESULTS: The rate of onset of the use dependent inhibition of conduction velocity and that of the square of conduction velocity were both faster than the simultaneously measured rate of onset of dV/dtmax inhibition induced by 20 mumol.litre-1 quinidine at high frequency stimulation. The relation between the rates of onset of the use dependent inhibition of conduction velocity (and the square of conduction velocity) and dV/dtmax became weak with low frequency stimulation and in the presence of 60 mumol.litre-1 quinidine. However, the recovery of conduction velocity (and the square of conduction velocity) from quinidine induced use dependent blockade, as measured by the extrastimulation method, appeared to be slower than the recovery of dV/dtmax. These results may be explained by a transient change in intracellular and intercellular conditions, such as an increase in internal resistance. CONCLUSIONS: The onset and recovery of the use dependent inhibition of conduction by antiarrhythmic drug may not always parallel the changes of the dV/dtmax of action potential in multicellular muscle preparations. PMID- 1884389 TI - Effect of ventilatory strategy on cardiac output during high frequency jet ventilation. AB - STUDY OBJECTIVE: The aim was to study the effects of changes in ventilation variables on cardiac function during high frequency jet ventilation. DESIGN: Controlled changes in mean airway pressure (2-10 cm H2O), tidal volume (4 and 8 ml), and frequency (4-8 Hz) were used to assess the effects of ventilatory variables on cardiac output in cats with normal and reduced lung compliance during high frequency jet ventilation. Cardiac output was continuously measured with an electromagnetic flow probe placed around the aorta. Respiratory compliance was reduced by lung lavage. EXPERIMENTAL MATERIAL: Seven anaesthetised adults cats, weight 3.0(SEM 0.2) kg, were used in the study. MEASUREMENTS AND MAIN RESULTS: Cardiac output fell as mean airway pressure was raised from 2 to 10 cm H2O at all frequencies and tidal volumes. At identical levels of minute ventilation and mean airway pressure, cardiac output was improved with combinations of smaller tidal volumes and higher frequencies. Reducing respiratory compliance by lung lavage dampened the effect of mean airway pressure on cardiac output, but maintained the relationship between ventilatory variables observed before lavage. CONCLUSION: At identical settings of minute ventilation and mean airway pressure, cardiac output may be improved with smaller tidal volumes during high frequency jet ventilation. PMID- 1884390 TI - Effect of acute anaesthesia on synthesis of contractile and non-contractile proteins of heart muscle and mixed proteins of types I and II fibre rich skeletal muscles of rat. AB - STUDY OBJECTIVE: The aim of the study was to determine whether the deleterious effects of anaesthesia on cardiac muscle function were due to disturbance of protein synthesis. Comparative investigations were made on anaerobic and aerobic skeletal muscles, and plasma insulin and growth hormone levels were also measured to see if these were mediating factors. DESIGN: Rats were subjected to acute methoxyfluorane anaesthesia for 10 min. At the end of the study they were killed and plasma growth hormone and insulin were measured. Rates of cardiac and skeletal muscle protein synthesis were also determined with a flooding dose of L[4-3H]phenylalanine. EXPERIMENTAL MATERIAL: Muscle samples were obtained from male Sprague-Dawley rats, weight 191-222 g. MEASUREMENTS AND MAIN RESULTS: Anaesthesia reduced the fractional rate of myocardial mixed protein synthesis and synthesis relative to RNA (p less than 0.05). The anaesthesia induced decrease in the synthesis rates of cardiac contractile proteins (p less than 0.05) was greater than the decrease in the non-contractile protein fractions (p greater than 0.05). Soleus (aerobic, Type I) and plantaris (anaerobic, Type II) muscle rates of protein synthesis were unaltered in response to anaesthesia (p greater than 0.05). Plasma insulin concentrations increased in response to acute anaesthesia (p less than 0.05), but the insulin effect was depressed by the flooding dose of phenylalanine (p less than 0.05). Plasma growth hormone levels were not altered in response to anaesthesia (p greater than 0.05). Thus, the changes in cardiac protein synthesis could not be ascribed to these hormones. CONCLUSIONS: Synthesis of cardiac contractile proteins is selectively sensitive to the effects of acute anaesthesia even in the presence of high plasma insulin concentrations. The fall in cardiac protein synthesis may be a result of the negative inotropic effects of general anaesthesia. PMID- 1884391 TI - Diltiazem at reperfusion reduces neutrophil accumulation and infarct size in dogs with ischaemic myocardium. AB - STUDY OBJECTIVE: The aim was to demonstrate the ability of diltiazem to protect the ischaemic myocardium in the course of coronary reperfusion, and to establish if an interaction with neutrophils is implied. DESIGN: Ischaemia was induced by occluding the left anterior descending coronary artery for 90 min followed by 6 h of reperfusion with a residual critical stenosis left in place. Three groups were studied: group 1 (control) received a saline perfusion; group 2 was given a bolus injection of 400 micrograms.kg-1 of diltiazem 10 min before reperfusion, followed by 4 micrograms.kg-1.min-1 perfusion until termination of experiment; group 3 was made neutropenic by injecting a neutrophil antiserum produced in rabbits and was then treated with diltiazem, as in the second group. SUBJECTS: 60 mongrel dogs of either sex were allocated at random into one of the three groups the day before the experiment. MEASUREMENTS AND MAIN RESULTS: Diltiazem plasma concentrations ranged from 68.6(SEM 10.0) to 102.5(15.2) micrograms.litre-1 during the study. Transmural collateral blood flow, measured with 153Gd microspheres 15 min after occlusion, and area at risk, evaluated by Evans blue perfusion, did not differ among the three groups. Infarct size, estimated by triphenyltetrazolium staining of heart slices and expressed as a percentage of area at risk, was less (p less than 0.05) in the diltiazem [20.5(5.2)%] and diltiazem plus neutropenia [17.6(5.4)%] groups compared to controls [39.8(6.9)%] but neutropenia added no significant benefit to diltiazem alone. The animals treated with diltiazem alone had lower serum creatine kinase levels than controls, at 5719(891) v 14,333(2885) IU.litre-1, p less than 0.05. The neutrophilia seen in controls was virtually absent in diltiazem dogs. Myocardial neutrophil accumulation estimated by scintigraphy of 111In labelled autologous neutrophils was much less in diltiazem than in control dogs, at 3948(1228) v 11,021(2081) 111In-neutrophil.g-1 of infarct, p less than 0.02. CONCLUSIONS: Diltiazem given during reperfusion reduces infarct size by a mechanism that includes an inhibition of neutrophil accumulation in the post-ischaemic myocardium. PMID- 1884392 TI - Contraction-excitation feedback in an ejecting whole heart model--dependence of action potential duration on left ventricular diastolic and systolic pressures. AB - STUDY OBJECTIVE: Contraction-excitation feedback may play a role in arrhythmogenesis in heart failure. The aims of this study were to determine whether contraction-excitation feedback has a significant effect on action potential duration within a physiological range of pressures, and to investigate the individual effects of left ventricular end diastolic and peak systolic pressures on action potential duration. DESIGN: A new model was developed for studying contraction-excitation feedback in a physiologically ejecting isolated heart preparation. Hearts were perfused via the left atrium, ejecting against an aortic afterload. By varying left atrial and aortic pressures, left ventricular end diastolic pressure and left ventricular peak systolic pressure were controlled independently. Intracellular potentials were recorded from the epicardium. EXPERIMENTAL MATERIAL: Hearts (n = 33) were obtained from guinea pigs weighing 300-350 g. MEASUREMENTS AND MAIN RESULTS: Increasing left ventricular end diastolic pressure from 0.3 to 1.1 kPa (2.2 to 8.3 mm Hg), at constant left ventricular peak systolic pressure, shortened action potential duration by 11.3(SEM 1.5) ms (p less than 0.0005). Action potential duration achieved a new steady state within 30 s of a change in end diastolic pressure. The changes were fully reversible. The effects of left ventricular peak systolic pressure variation at constant left ventricular end diastolic pressure were less marked. Increasing left ventricular peak systolic pressure from 10.3 to 13.1 kPa (75 to 100 mm Hg) shortened action potential duration by 2.1(0.7) ms (p less than 0.01). Reduction of aortic pressure below 8 kPa had variable effects on action potential duration, reflecting the development of ischaemia. CONCLUSION: The results show the existence of contraction-excitation feedback in a physiologically ejecting whole heart preparation and suggest that raised end diastolic pressure may contribute to arrhythmogenesis in heart failure. PMID- 1884393 TI - Current bibliography of cell calcium prepared by the University of Sheffield Biomedical Information Service. PMID- 1884394 TI - The Ca2+ release activities of D-myo-inositol 1,4,5-trisphosphate analogs are quantized. AB - Comparison is made between several synthetic stereo and positional isomers of D myo-inositol 1,4,5-trisphosphate (D-myo-1,4,5-IP3) with respect to their ability to mobilize calcium from the internal stores of saponin-permeabilized rat basophilic leukemia cells. D- and L-myo-Inositol 1,4,5-trisphosphates, D- and L myo-inositol 2,4,5-trisphosphates, D- and L-chiro-inositol 1,3,4-trisphosphates, D,L-trans-1,2-cyclohexane-diol bisphosphate, D,L-myo-inositol 4,5-bisphosphate, L glycerol 1,2-bisphosphate, glycerol 1,3-bisphosphate and D,L-(1R,3R,4R)-1 phosphoryloxymethyl-trans-3,4-cyclohexanediol bisphosphate were tested. The analogs, each of which contains a vicinal trans-1,2-diol-bisphosphate motif, displayed potencies that were distributed over a 10(4)-fold range of concentration and fell into 4 distinct classes of activity. PMID- 1884395 TI - Evidence that binding of Indo-1 to cardiac myocyte protein does not markedly change Kd for Ca2+. AB - Quantitative measurement of [Ca2+]i with the fluorescent Ca(2+)-indicators Indo-1 and Fura-2 is complicated by the possibility that the value of the dissociation constant (Kd) may be influenced by binding to intracellular proteins. We investigated this question in cultured chick ventricular myocytes by use of two different Indo-1 calibration methods. First, the Indo-1 fluorescence ratio (R) (400/500 nm) was measured in beating myocytes loaded by exposure to Indo-1/AM. Then, cells were exposed to the Ca2+ ionophore Br A-23187 and fluorescence ratio was measured in the presence of 500 nM Ca2+ (EGTA-Ca2+ buffer). Subsequently cells were permeabilized to Ca2+ by a 1 min exposure to 25 microM digitonin in the presence of 'zero' Ca2+ (10 mM EGTA) and saturating 1 mM Ca2+ to obtain Rmin, Rmax and beta. We then calculated [Ca2+]i from the formula ([Ca2+]i = Kd [( R - Rmin)/(Rmax - R)]beta). With Kd = 250 nM, calculated systolic [Ca2+]i was 750 +/- 44 nM and diastolic 269 +/- 19 nM (means +/- SEM, n = 16). The R value calculated for an assumed [Ca2+]i = 500 nM using the above formula and digitonin derived constants was very similar to the value measured using Br A-23187 (digitonin, 0.67 +/- 0.03: Br A-23187, 0.66 +/- 0.03, ns). As the Br A-23187 method is independent of the value chosen for Kd, we conclude that the Kd of 250 nM for Indo-1 measured in free solutions closely approximates the Kd for intracellular Indo-1 in these cells, and that therefore the Kd of Indo-1 for Ca2+ does not appear to be markedly affected by binding to proteins or other intracellular molecules. PMID- 1884396 TI - Production of a monoclonal antibody strongly reacting with immature thymic T lymphocytes and its immunohistological application. AB - A monoclonal antibody Th-5 has been produced against mouse immature thymic lymphocytes and employed to study the process of T cell differentiation in the thymus. Immunohistologically, Th-5 positive thymic T lymphocytes were first found at Day 12 of gestation. They increased in number as well as staining intensity until Day 18 of gestation and decreased thereafter. Th-5 antigen expression was not seen in lymphoid cells in the fetal liver. In the newborn thymus, lymphocytes in the subcapsular layer were still strongly positive, while other cortical lymphocytes became moderately positive for Th-5. Th-5 positiveness was more pronounced in the medulla than in the cortex in the thymus of young adult mice. The staining pattern of Th-5 in the thymus was apparently different from those with other T cell markers (Thy-1, CD3, CD4, CD5, CD8) including J11d, Pgp-1, IL 2R, and 3A10 (TCR gamma delta). Flow cytometric analyses showed that the expression of Th-5 was mostly associated with the Thy-1 antigen. However, the fluorescent intensity of Th-5 gradually declined with ontogenic development of the thymus, and the molecular size of the antigen was approximately 100 kDa, which is different from Thy-1 antigen (25-30 kDa). Considering these findings, the strong expression of Th-5 could be one of the markers of immature thymic T lymphocytes in the early phase of the ontogenic development. PMID- 1884397 TI - Interleukin 5 (IL-5) can act in G0/G1 to induce S phase entry in B lymphocytes from normal and autoimmune strain mice and in transformed leukemic B cells. AB - In addition to its ability to enhance antibody secretion, Interleukin 5 (IL-5) enhances murine B lymphocyte proliferation. This so-called growth factor activity has been amply demonstrated by many laboratories assessing thymidine incorporation or cell recovery. Attempts to actually quantitate the fraction of fresh splenic B cells responding to IL-5, by limiting dilution analysis or other means, with few exceptions have yielded disappointingly small numbers--generally between 1 and 5%, or perhaps less. We have recently identified the peritoneal cavity as a reservoir rich in IL-5-responsive B cells. In this report, we provide independent corroboration of this high IL-5 reactivity by means of cell cycle analysis. Low-density peritoneal B cells, more than 90% of which are in G0 and G1 phases, were stimulated with polyclonal activators in the presence of mitotic inhibitors. Frequencies of IL-5-responsive B cells were measured by observing the differences in the proportions of cultured cells entering S and later phases in the presence, compared to the absence, of IL-5. Some 10 to 20% more of the low density peritoneal B cells from normal mice entered S phase when IL-5 was present with LPS + DXS. A similar IL-5-mediated elevation in the frequency of S phase entry was seen with peritoneal B cells from the autoimmune mouse strain NZB. Furthermore, a measurable fraction of peritoneal B cells from these mice were even capable of responding to IL-5 alone. These IL-5-induced increases could be blocked by anti-IL-5 mAb. About 30% of the BCL1 leukemic B cell line initiated DNA replication when stimulated with IL-5 alone. Hence, IL-5-responsive B cell fractions have been measured for some normal, autoimmune strain and transformed leukemic B cell phenotypes. In addition to quantitating the proportion of IL-5 responsive B cells, these experiments formally demonstrate that IL-5 can act in the G1 phase to increase S phase entry. PMID- 1884398 TI - Induction of interleukin-1 in human monocytes by the superantigen staphylococcal enterotoxin A requires the participation of T cells. AB - Nanogram quantities of the bacterial superantigen Staphylococcal Enterotoxin A (SEA) induced significant amounts of extracellular IL-1 alpha and IL-1 beta in human peripheral blood mononuclear cells. Induction of maximal IL-1 alpha and IL 1 beta levels by lipopolysaccharide (LPS) required microgram quantities. LPS induced detectable extracellular IL-1 content within 3-6 hr and maximal levels were detected already after 12 hr. Induction of IL-1 production by SEA showed a delayed release with peak values after 24-48 hr. IL-1 beta was the major species of IL-1 seen in both SEA- and LPS-stimulated culture supernatants. SEA was in general a relatively stronger inducer of extracellular IL-1 alpha than LPS. SEA induced extracellular IL-1 production in human monocytes was entirely dependent on the presence of T cells, whereas addition of T cells to LPS-stimulated purified human monocytes only marginally enhanced the extracellular IL-1 production. The capacity to induce extracellular IL-1 production in monocytes in response to SEA was high in the CD4+ 45RO+ memory T cell subset, whereas CD4+ 45RA+ naive T cells and CD8+ T cells had lower IL-1-inducing capacity. The T cell help for IL-1 production could not be replaced by a panel of T cell-derived recombinant lymphokines added to SEA-stimulated monocytes, including IFN-gamma and TNF, indicating the participation of cell membrane-bound ligands or hitherto unidentified soluble mediators. PMID- 1884399 TI - Induction of local inflammation by recombinant human platelet factor 4 in the mouse. AB - Platelet factor 4 (PF-4) has been shown to be chemotactic for neutrophils and monocytes in vitro. To assess whether these observations have in vivo relevance, we tested the ability of recombinant human PF-4 (rPF-4) to induce acute and chronic dermal inflammation in the mouse. When injected as a single dose intradermally, rPF-4 induced an acute inflammatory response that peaked at 6 to 12 hr and which resolved by 36 hr. Injection of an equivalent amount of cytochrome c, buffer alone, or an amino-terminal PF-4 peptide failed to elicit a significant inflammatory response; however, the carboxy-terminal PF-4 peptide retained proinflammatory properties. The inflammatory infiltrate induced by a single injection of either rPF-4 or the 41 amino acid carboxy-terminal peptide was composed of neutrophils and smaller numbers of mononuclear cells. Repeated injection of rPF-4 resulted in nearly equal numbers of neutrophils and mononuclear cells. Moreover, marked dermal fibrosis developed after only 5 days of daily injection of rPF-4. Although relatively high concentrations of rPF-4 were required to elicit an inflammatory response, these concentrations may be locally attainable during platelet aggregation. Our findings thus support the hypothesis that PF-4 may contribute to the development of inflammatory responses at sites of platelet aggregation. PMID- 1884400 TI - Sensitization in vitro of human peripheral blood mononuclear cells to phenolic glycolipid 1 of Mycobacterium leprae in liposomes. AB - Study of primary immune responses in leprosy has been limited, since disease becomes manifest long after infection or is not detectable. To study primary immune responses, we immunized in vitro human peripheral blood mononuclear cells from unexposed individuals using phenolic glycolipid 1 (PGL-1), an important water-insoluble antigenic constituent of Mycobacterium leprae. PGL-1, encapsulated in liposomes, induced lymphoproliferation or, less frequently, suppression of lymphoproliferation in 11-day lymphocyte cultures. The primary lymphocyte responses resembled those elicited with keyhole limpet hemocyanin (KLH). HLA-DR2 expression, associated with tuberculoid leprosy, did not influence the outcome of in vitro sensitization. The association of HLA-DR2 and tuberculoid leprosy is not explained by differential ability to generate primary lymphoproliferative responses to PGL-1 or KLH. We have extended in vitro sensitization methodology to include a water-insoluble antigen in antigen-bearing liposomes. This methodology is potentially useful for studies of immunogenetics and immunopathology, and for vaccine research. PMID- 1884401 TI - Optimising a limiting dilution culture system for quantitating frequencies of alloreactive cytotoxic T lymphocyte precursors. AB - We have developed a limiting dilution assay for estimating the frequencies of allo-MHC reactive cytotoxic T lymphocyte precursors (CTL-p) in peripheral blood. The culture conditions were optimised in order to give maximum sensitivity while at the same time maintaining a high degree of specificity. While the addition of filler cells, interleukin-1 and interleukin-4 were unnecessary, the addition of interleukin-2 (IL-2) was crucial for optimal expansion of the CTL-ps. However, excess exogenous IL-2 was found to give rise to nonspecific cytotoxicity, and 5 U/ml final concentration of recombinant IL-2 added on Days 3 and 6 was optimal. The establishment of baseline control cultures for determining positivity and negativity of the test cultures is discussed. Using this modified assay system, we demonstrated that the culture conditions fulfil "single hit" criteria and that the assay is highly specific. PMID- 1884402 TI - [Aortopulmonary window in 10 children]. AB - The authors present their diagnostic and therapeutic experience with aortopulmonary window in 10 children. As it threatens, in particular if combined with other heart diseases, the majority of children with development of early irreparable changes in the pulmonary circulation it is important to diagnose the defect, preferably by echocardiography and treat it already in childhood. PMID- 1884403 TI - [Arteriovenous fistula for chronic hemodialysis in children]. AB - The authors give an account of their experience with an artificial arteriovenous fistula of the needs of chronic haemodialysis. During a five-year period they established an A-V fistula with prolonged satisfactory function in seven children aged 5-14 years. In none of the patients the fistula, made as suggested by Cimin and Bresciu on the wrist of the non-dominant extremity, failed. Development and arterialization of the venous drainage system on the fore arm occurred 6-8 weeks after establishment of the fistula. Despite miniature dimensions of the artery and vein a functioning radiocephalic fistula in children with chronic renal insufficiency is a suitable method to overcome the period before transplantation of the kidney. PMID- 1884404 TI - [24-hour esophageal pH measurement in 52 children with gastroesophageal reflux]. AB - The authors give an account of their experience with 24-hour pH metry of the oesophagus in children. They made 56 examinations in 52 patients with different clinical complications of gastrooesophageal reflux (GER). The pathological finding during oesophageal pH-metry was in the great majority consistent with the pathological finding during oesophageal manometry. Of 52 children 18 patients were indicated for surgery on account of GER. The authors emphasize the advantages of 24-hour oesophageal pH-metry in particular as an auxiliary method in indications for surgery of gastrooesophageal reflux. PMID- 1884405 TI - [Phosphoethanolamine in the blood and urine in sick children]. AB - The phosphoethanolamine (PEA) concentration in morning urine was assessed by liquid chromatography in 866 patients examined because of suspected impaired aminoacid metabolism. In 763 patients the blood was also examined. A serum concentration of PEA above 10 mumol/l was recorded in 2.1%. The concentration of PEA in urine above 10 mmol/mol creatinine was recorded in 42%. The authors revealed a significant relationship between urinary PEA excretion and the patient's age. The urinary PEA concentrations are higher during the first weeks and months of life, in older children and during adolescence its excretion declines and this trend was recorded also in the author's group of patients. In a group of 111 infants with impaired function of the CNS, in 66 infants with systemic skeletal affections and in 73 infants with hepatopathies a significantly higher mean urinary PEA concentration was found that in the control group of healthy infants. In children aged 3-14 years and in the group of older children the mean PEA concentration was elevated only in patients with systemic skeletal affections, even after elimination of patients with hypophosphatasia. Long-term or intermittently increased PEA excretion is a manifestation of specific metabolic disease only in hypophosphatasia. In other diseases it can be interpreted as a secondary finding conditioned by an impaired phospholipid metabolism at the level of cellular membranes in the CNS, liver or skeleton. PMID- 1884406 TI - [Clinical morphology of ventricular septal defects]. AB - The authors give an account of morphological characteristics of different types of ventricular septal defects. They demonstrate their typical pictures obtained by angiocardiographic and echocardiographic examination. The investigation is based on analysis of 295 children with a cinematographically confirmed diagnosis and 75 necroptic preparations of the heart with a ventricular septal defects. PMID- 1884407 TI - [Risk factors for ischemic heart disease in the offspring of persons with a history of early onset of this disease]. AB - The investigation was focused on assessment of the frequency of risk factors for the development of ischaemic heart disease (IHD)--hyperlipoproteinaemia, smoking, arterial hypertension and obesity--in the offspring of subjects suffering from the disease before the age of 55 years. Among grade I 126 offspring they recorded in 6.4% hyperlipoproteinaemia, in 29.4% smoking, in 2.4% arterial hypertension and in 16.7% obesity. The author draws attention to the fact that almost 40% of the offspring under 35 years of age of subjects with a history of early IHD have at least one risk factor for the development of the disease. These subjects are a high group which should be screened and followed up within the framework of primary prevention of cardiovascular diseases. PMID- 1884408 TI - [Advances in the treatment of renal hypertension in childhood]. PMID- 1884409 TI - [Hearing and treatment of neonates with gentamycin]. AB - The authors examined two groups of children treated during neonatal period with high doses of Gentamycin. The reasons for Gentamycin treatment at the intensive care unit were infection of the CNS, pneumopaties, intracranial haemorrhagiae, cerebral oedema and other causes. The first group of children was treated in 1981, the second one in 1986. Both groups were examined in 1987. All children were evaluated to objective hearing tests, impedance audiometry by acoustically evoked potentials of the brain stem. Children of the first group examined during their fifth or sixth year were also submitted to a hearing test. The control group was formed by children born in 1986 treated at the intensive care unit with similar indications but who were not given Gentamycin. A total of 51 children were examined. Twenty-two children examined at the age of five had no hearing impairment. Acoustically evoked potentials of the brain stem have a wide variability which may be the manifestation of the disease which led to admission to the intensive care unit. Therefore it should be conceived as a screening examination and the revealed pathological findings should be verified by repeated examinations. Possible hearing disorders should be confirmed at a later age by conventional examinations. PMID- 1884410 TI - [Modern possibilities of group therapy in obesity in a pediatric health facility]. PMID- 1884411 TI - [How can we really help obese children?]. PMID- 1884412 TI - [The Proteus syndrome]. PMID- 1884413 TI - [2 cases of spontaneous intracerebral hematoma in children]. PMID- 1884414 TI - [Case report of long-term survival in acute leukemia]. PMID- 1884415 TI - [The important role of secondary prevention of congenital defects in decreasing early fetal losses in the Czech Republic in 1989]. PMID- 1884416 TI - [Algorithms for diagnosing the most frequent endocrine diseases in clinical practice]. PMID- 1884417 TI - [Experience with implementation of a cardiovascular program for the pediatric population in the Cadca District]. PMID- 1884418 TI - [A summer camp for children with chronic hematologic diseases]. PMID- 1884419 TI - [Histiocytosis X in siblings]. PMID- 1884421 TI - [Arachnoid cysts]. PMID- 1884420 TI - [Accidental ingestion of 120 tablets of sodium fluoride in a 3-year-old child]. PMID- 1884422 TI - [Trends in pediatric endocrinology]. PMID- 1884423 TI - [The battered child syndrome]. PMID- 1884424 TI - [Quinolones in pediatrics?]. PMID- 1884425 TI - [Echocardiographic parameters of the left ventricle in children involved in sports]. AB - The authors investigated, using computer-assisted one-dimensional echocardiography, the influence of systematic two-year sports training on the heart of children engaged in sports (ice hockey n = 20) and a control group of boys not engaged in sports training (n = 25) of the same age (12.6 +/- 0.3 years). At the beginning of the investigation and after two years' training between the two groups no significant differences were found in the following parameters: fractional systolic reduction of the inner diameter of the left ventricle, fractionated systolic enlargement of the interventricular septum, relative width of the left ventricular wall, index of asymetricity of left ventricular hypertrophy and weight of the left ventricle. In none of the investigated parameters the values in sportsmen were beyond the physiological range. The authors did not observe in sportsmen a tendency towards concentric or assymetric hypertrophy of the left ventricle. PMID- 1884426 TI - Reactive oxygen and ischemia/reperfusion injury of the liver. AB - Pharmacological experiments suggested that reactive oxygen species contribute to ischemia-reperfusion injury of the liver. Since there is no evidence that quantitatively sufficient amounts of reactive oxygen are generated intracellularly to overwhelm the strong antioxidant defense mechanisms in the liver and cause parenchymal cell injury, the role of reactive oxygen in the pathogenesis remains controversial. This paper reviews the data and conclusions obtained with pharmacological intervention studies in vivo, the sources of reactive oxygen in the liver as well as the growing evidence for the importance of liver macrophages (Kupffer cells) and infiltrating neutrophils in the pathogenesis. A comprehensive hypothesis is presented that focuses on the extracellular generation of reactive oxygen in the hepatic sinusoids, where Kupffer cell-derived reactive oxygen species seem to be involved in the initial vascular and parenchymal cell injury and indirectly also in the recruitment of neutrophils into the liver. Reactive oxygen species may also contribute to the subsequent neutrophil-dependent injury phase as one of the toxic mediators released by these inflammatory cells. PMID- 1884427 TI - The origin of the DNA induced circular dichroism of CC-1065 and analogs. AB - The calf thymus DNA (CT-DNA) and poly(dI-dC).poly(dI-dC) binding properties of the natural antitumor antibiotic CC-1065 and selected analogs of CC-1065 were studied by circular dichroism (CD) and absorbance methods. The results indicate that the intense long wavelength DNA-induced CD band of these molecules originates from a chiral electronic transition which is delocalized over the whole molecule. Both the covalently bound species (N-3 adenine adduct) and the reversibly bound species exhibit the characteristic spectral behavior of an inherently dissymmetric chromophore when these agents bind within the minor groove of B-form DNA. This mechanism of optical activity accounts for why CC-1065 shows a weak CD in buffer but a very intense induced CD at long wavelength when bound to DNA, why the intensity of the induced CD of CC-1065 analogs depends upon how many fused ring systems the analog contains, and why covalently bound analogs having the mirror image configuration of the natural configuration also exhibit an intense positive induced CD band at long wavelength. PMID- 1884428 TI - Aqueous cigarette tar extracts damage human alpha-1-proteinase inhibitor. AB - The elastase inhibitory capacity (EIC) of human alpha-1-proteinase inhibitor (alpha 1PI) is severely compromised by aqueous cigarette tar extract (ACTE). An aqueous extract of the tar from two cigarettes causes a loss of EIC of at least 60% in 24 h at 37 degrees C (pH 7.4) and the damaging capability of the ACTE is retained for many hours. Hydrogen peroxide appears to be an essential component of the mechanism by which ACTE damages alpha 1 PI, since catalase substantially protects alpha 1PI from ACTE-mediated damage. Only mild protection is offered by 10 mM diethylenetriamine pentaacetic acid, indicating only a minor role for transition metal ions in the alpha 1PI-damaging process. Hydroxyl radicals are unlikely agents of alpha 1PI damage in the ACTE system, as judged from hydroxyl radical scavenger studies. Ascorbate and various thiols offer protection to different degrees, dependent on the incubation conditions. Of several amino acids tested, cysteine and methionine (but not methionine sulfoxide) are the only two that protect alpha 1PI. We suggest that components of cigarette smoke particulate matter extracted into the aqueous lung fluid environment may cause local deficiencies in alpha 1PI in smokers' lungs. PMID- 1884429 TI - Metabolic activation of the herbicide dichlobenil in the olfactory mucosa of mice and rats. AB - The metabolic activation of the herbicide dichlobenil (2,6-dichloro[ring 14C]benzonitrile) in the olfactory mucosa of C57BL mice and Sprague-Dawley rats was examined. In homogenates of the olfactory mucosa (mouse 1000 x g supernatants; rat microsomes), dichlobenil was metabolized and covalently bound to protein. The apparent Km, Vmax and V/K values showed that the olfactory mucosa had both a higher affinity for dichlobenil and a higher capacity/mg protein to activate dichlobenil in comparison to the liver. The covalent binding was dependent on NADPH and was inhibited by the addition of dithionite, metyrapone and glutathione indicating an oxidative cytochrome P-450 dependent activation of dichlobenil into an electrophilic intermediate. The covalent binding was also inhibited by the addition of superoxide dismutase whereas catalase, mannitol or dimethylsulfoxide had no effect indicating the involvement of O2- but not of H2O2 or OH. in the activation. In explants of the olfactory mucosa incubated with [14C]dichlobenil a preferential covalent binding was observed in the Bowman's glands suggesting an activation of dichlobenil in these structures. The highly efficient metabolic activation of dichlobenil to reactive intermediates in the olfactory mucosa is suggested to be of importance for the potent dichlobenil induced toxicity in this tissue. PMID- 1884430 TI - DNA hydroxyethylation by hydroxyethylnitrosoureas in relation to their organ specific carcinogenicity in rats. AB - N-Hydroxyethylnitroso-N'-ethylurea (HEENU) and N-hydroxyethylnitroso-N' chloroethylurea (HCNU) are two of the few nitrosoureas which induce hepatocellular tumours in rats without further treatment. In the present study we have investigated whether this is due to selectively elevated levels of DNA hydroxyethylation in the target tissue. Formation of the promutagenic base O6 hydroxyethyldeoxyguanosine (O6-HEdG) in various rat tissues was determined by immuno-slot-blot assay. After a single dose by gavage (0.36 mmol/kg body wt) of HEENU, initial levels of O6-HEdG in liver and brain were close to the detection limit of 1.5 mumol/mol deoxyguanosine. In liver, steady state concentrations of 3.5 mumol/mol were reached after 6 h and maintained for at least 18 h. In brain, O6-HEdG levels were 1.7 mumol/mol after 6 h and 3.0 mumol/mol after 24 h. In a second experiment, the formation of O6-HEdG was assessed in target and non-target tissues 6 h after a single dose by gavage (0.36 mmol/kg) of HEENU, HCNU or hydroxyethylnitrosourea (HENU), which is not hepatocarcinogenic. The extent of DNA hydroxyethylation was greatest with HENU in all tissues examined. Concentrations of O6-HEdG were highest in liver (37.2 mumol/mol), followed by kidney (23.3 mumol/mol), lung (18.9 mumol/mol), brain (6.8 mumol/mol) and testes (3.8 mumol/mol). With HEENU and HCNU, levels of 1.4-3.3 mumol O6-HEdG/mol dG were observed in all tissues. In vitro, the alkylation reactions for all three compounds were nearly complete within 6 h. On a molar basis, yields of O6-HEdG in vitro were similar for HENU and HCNU and 3.7 times lower for HEENU. This suggests that the in vivo reactions of the dialkylnitrosoureas are by pathways other than or in addition to those occurring in vitro. We conclude that the hepatocarcinogenicity of HCNU and HEENU cannot be explained on the basis of their reaction with cellular DNA. PMID- 1884431 TI - Hydroxylation and deglycosylation of 2'-deoxyguanosine in the presence of magnesium and nickel. AB - Nickel (Ni), a carcinogenic and genotoxic metal, has been shown to enhance deglycosylation and hydroxylation of 2'-deoxyguanosine (dG) that has been caused by ascorbic acid and H2O2. There is evidence that Mg is a competitive antagonist of the toxicological effects of Ni. A factorial design was used to examine the interactive influence of Mg and Ni on the deglycosylation and hydroxylation of dG under a range of pH conditions in which ascorbate (Ascb) and H2O2 were added. Formation of guanine (Gu) (deglycosylation) and 8-hydroxy-2'-deoxyguanosine (8-OH dG) (hydroxylation) appeared in large amounts in samples in which both H2O2 and Ascb were present. The largest amounts of Gu appeared where both Ni or magnesium (Mg) were present. When Mg alone was present, the amounts of Gu was intermediate between these two. Slightly less 8-OH-dG was formed where only Mg was present. The reaction mixtures were more sensitive to the pH than to the respective presence or absence of metals. At slightly acid or neutral pH (6.2-7.0) large amounts of both Gu and 8-OH-dG were formed. Gu formation decreased dramatically between pH 7.0 and 7.2. There was no 8-OH-dG formed at pH 7.8 and only small amounts at pH 7.6. The formation of 8-OH-dG was generally less where Mg was present. When Ni was absent, 8-OH-dG formation was greater in the pH 6.8 mixtures. The formation of Gu and 8-OH-dG from 2'-deoxyguanosine are directly a function of pH. Slight changes in pH greatly effected the formation of these biomarkers of oxidatively damaged DNA. Additional research is needed to determine if this is a cause or effect, i.e. does pH enhance toxicity conditions, thus permitting formation of 8-OH-dG, or does pH permit the reaction to proceed. PMID- 1884433 TI - Microvascular exchange during burn injury: IV. Fluid resuscitation model. AB - The present work is a continuation of studies concerned with mathematical modelling and simulation of microvascular fluid and protein exchange following burn injuries [Bert et al.: Circulatory Shock 28: 199-219, 1989: Bowen et al.: Circulatory Shock 28: 221-233, 1989]. The model has been extended to include the effects of different types of fluid resuscitation on the circulatory and microvascular exchange systems. The model and a statistical fitting procedure were used to find the ranges of fitting parameter values that best describe the changes in interstitial fluid volume and protein mass as well as transcapillary protein extravasation for three sets of experiments (no resuscitation, resuscitation with Ringer's or resuscitation with plasma). Typical changes in mass exchange related parameters postburn that resulted in simulation predictions which were a good fit to the experimental data include: an increase in the large pore pathway for protein of 100 times in the injured skin and 5 times in non injured skin and skeletal muscle, an increase in fluid filtration coefficients in injured skin of 10 times and an instantaneous decrease of 50% in the area available for exchange in injured skin at the time of the burn. PMID- 1884432 TI - The antioxidant action of ketoconazole and related azoles: comparison with tamoxifen and cholesterol. AB - The azole antifungal drug ketoconazole was found to inhibit Fe(III)-ascorbate dependent lipid peroxidation using either rat liver microsomes or ox-brain phospholipid liposomes as the substrate. It also inhibited microsomal peroxidation induced by the Fe(III)-ADP/NADPH system. The related azoles, miconazole and clotrimazole, were much weaker inhibitors than ketoconazole. Ketoconazole was approximately equipotent with the triphenylethylene anticancer drug tamoxifen in the microsomal system and was almost as effective as 4 hydroxytamoxifen in the liposomal system. Ketoconazole introduced into phospholipid liposomes during their preparation inhibited Fe(III)-ascorbate induced lipid peroxidation to a greater extent than similarly introduced cholesterol, ergosterol or tamoxifen. Miconazole and clotrimazole were again poor inhibitors of lipid peroxidation in this system. These antioxidant effects of ketoconazole may be due to membrane stabilization in the systems used. The implications of our findings for the clinical applications of these drugs are discussed. PMID- 1884434 TI - Hyperdynamic sepsis in baboons: I. Aspects of hemodynamics. AB - The baboon has a number of advantages as a shock model, as its physiological as well as its biochemical behaviour is similar to man. Therefore we have tried to set up a model to mimic the early hyperdynamic phase of clinical sepsis. Seven baboons, 21-25 kg body weight were kept under EEG servocontrolled anesthesia for 8 hr. During this time live E. coli (ATC #33985) 2 x 10(10) BW/8 hr were continuously infused intravenously. Adequate fluid supply with Ringer's solution (up to 40 ml/kg/hr) was given to keep the pulmonary artery wedge pressure at baseline levels; this procedure resulted in a hyperdynamic response with a cardiac output (CO) 20-35% above baseline and a decrease (20-39%) in mean arterial pressure (MAP), leading to a 50% decrease in peripheral resistance. The pulmonary vascular changes were reflected in an increase of the mean pulmonary pressure (PA) to 42% above baseline and a marked rise in pulmonary vascular resistance (PVR) to 50% above baseline with no additional changes in pulmonary gas exchange. After 8 hr both CO and MAP were inversely correlated (r = 0.9-1) with dramatically increased catecholamine plasma levels (15 times above baseline). With continuous infusion of live E. coli (blood levels 10(5)-10(6) CFU/ml) and massive fluid supply we have successfully mimicked hyperdynamic sepsis with severe organ failure after an 8-hr observation period. PMID- 1884435 TI - Extracellular muscle surface pO2 and pH heterogeneity during hypovolemia and after reperfusion. AB - Tissue pO2 (ptO2) and pH (ptH) in skeletal muscle are known to be affected at an early stage of hemorrhage. This study examines the effects of hypovolemia on the extracellular ptO2 and ptH distributions at multiple tissue sites using a recently developed multipoint microelectrode, that provides simultaneous measurements of ptO2 and ptH. The results show that the development of tissue acidosis occurs in spatially different patterns and that the magnitude of the acidosis at some tissue sites is larger and remains longer than previously known. The changes described are believed to be due to the heterogeneous blood flow seen during shock and after reperfusion. The degree of local acidosis was correlated to the relative decrease in oxygen tension at that particular site. These new findings can be of importance for the development of future resuscitative measures as well as in constructing patient monitoring systems. PMID- 1884436 TI - Influence of pentoxifylline and related analogues in endotoxemic renal failure. AB - Acute kidney dysfunction, manifested by reductions in renal blood flow and glomerular filtration rate with increased renal vascular resistance, is a common finding in septic shock. In an attempt to halt the progressive renal dysfunction, the hemorheologic methylxanthines, pentoxifylline (1, 5, or 10 mg/kg of PTX) and 2 structurally-related analogues, 5 mg/kg of HWA-138 and 5 mg/kg of HWA-448, or saline wee given 7.5 hr after endotoxin infusion in the rat. Renal function, assessed by single-dose inulin clearances (CIN), was measured at 6 hr after the infusion of endotoxin and also 1 hr following the drug treatment. The mean CIN at 6 and 9 hr after endotoxin infusion were 2- and 3-fold decreased compared with control rats given either saline or 5 mg/kg of PTX. Although renal function declined in all rats throughout the study period, the reduction in renal function was markedly slowed in endotoxemic rats given 10 mg/kg of PTX or 5 mg/kg of HWA 448 compared with untreated controls (74 +/- 9% and 77 +/- 9 vs. 47 +/- 12% of 6 hr CIN at 9 hr, respectively; P less than 0.01). Similar results were found with single doses of 5 mg/kg of PTX or HWA-138; PTX 1 mg/kg had a modest beneficial effect on renal function. There was no evidence of vascular congestion in endotoxemic kidneys upon histologic examination. These data suggest the potential benefit of PTX and related methylxanthines in stopping progressive renal damage associated with septic shock. PMID- 1884437 TI - Trends in use of coronary angiography in subacute phase of myocardial infarction. AB - BACKGROUND: Most patients do not undergo acute reperfusion after myocardial infarction, and which of these patients should undergo coronary angiography is still debated. METHODS AND RESULTS: We analyzed the 1-year clinical outcomes and rates of coronary angiography performed as late as 60 days after myocardial infarction in 3,804 patients admitted between 1979 and 1988 and followed in six different centers. Patients less than 75 years old were classified into low-, medium-, and high-risk groups using a multivariate analysis of historical and clinical variables gathered during the first 8 hospital days. Patients who underwent early reperfusion (17%, all after 1984) were analyzed separately. To analyze time trends, patients were compared before and after mid-1984. Mortalities from day 9 through 1 year were similar for the two time periods in the low- (3.3% versus 2.5%) and medium-risk (7.4% versus 5.6%) groups, but mortality was lower for the high-risk group after 1984 (31.6% versus 20.0%). The proportion of patients undergoing coronary angiography increased dramatically in each group after 1984 (low risk, 18% versus 48%; medium risk, 23% versus 49%; high risk, 10% versus 32%, before and after 1984, respectively). Furthermore, a large percentage of patients (more than 40%) in the low-risk group did not have at least one of the indications for coronary angiography recently recommended by a joint task force. Among patients undergoing coronary angiography, the proportion of patients with three-vessel coronary artery disease decreased after 1984, whereas the proportion undergoing mechanical revascularization in the year after infarction increased in all risk groups. CONCLUSIONS: Despite the recent development of noninvasive techniques with high sensitivity for detecting high risk patients after myocardial infarction, coronary angiography is being performed increasingly in all patients, including those determined to be at low risk for complications based on clinical data. The economic consequences of such a trend could be considerable, and its impact requires careful analysis. PMID- 1884438 TI - Left ventricular pressure-volume and Frank-Starling relations in endurance athletes. Implications for orthostatic tolerance and exercise performance. AB - BACKGROUND: Endurance athletes have a high incidence of orthostatic intolerance. We hypothesized that this is related to an abnormally large decrease in left ventricular end-diastolic volume (LVEDV) and stroke volume (SV) for any given decrease in filling pressure. METHODS AND RESULTS: We measured pulmonary capillary wedge (PCW) pressure (Swan-Ganz catheter), LVEDV (two-dimensional echocardiography), and cardiac output (C2H2 rebreathing) during lower body negative pressure (LBNP, -15 and -30 mm Hg) and rapid saline infusion (15 and 30 ml/kg) in seven athletes and six controls (VO2max, 68 +/- 7 and 41 +/- 4 ml/kg/min). Orthostatic tolerance was determined by progressive LBNP to presyncope. Athletes had steeper slopes of their SV/PCW pressure curves than nonathletes (5.5 +/- 2.7 versus 2.7 +/- 1.5 ml/mm Hg, p less than 0.05). The slope of the steep, linear portion of this curve correlated significantly with the duration of LBNP tolerance (r = 0.58, p = 0.04). The athletes also had reduced chamber stiffness (increased chamber compliance) expressed as the slope (k) of the dP/dV versus P relation (chamber stiffness, k = 0.008 +/- 0.004 versus 0.031 +/- 0.004, p less than 0.005; chamber compliance, 1/k = 449.8 +/- 283.8 versus 35.3 +/- 4.3). This resulted in larger absolute and relative changes in end-diastolic volume over an equivalent range of filling pressures. CONCLUSIONS: Endurance athletes have greater ventricular diastolic chamber compliance and distensibility than nonathletes and thus operate on the steep portion of their Starling curve. This may be a mechanical, nonautonomic cause of orthostatic intolerance. PMID- 1884439 TI - Epicardial and endocardial mapping of ventricular tachycardia in patients with myocardial infarction. Is the origin of the tachycardia always subendocardially localized? AB - BACKGROUND: Left ventricular endocardial reentry is the conventional concept underlying surgery for ventricular tachycardia (VT). We assessed the incidences of patterns showing complete reentry circuits at either the subendocardial or subepicardial level and of patterns in which left ventricular endocardial mapping could only in part account for a reentrant mechanism. METHODS AND RESULTS: We retrospectively analyzed epicardial and left ventricular endocardial isochronal maps of 47 VTs induced in 28 patients with chronic myocardial infarction (inferior, 14 patients; anteroseptal, 14 patients). Electrograms were recorded intraoperatively from 128 sites with epicardial sock and transatrial left ventricular endocardial balloon electrode arrays. Given the methodology used in this study, the mapping characteristics of the tachycardias suggested five types of activation patterns: 1) complete (90% or more of VT cycle length) subendocardial reentry circuits in seven VTs (15%) and seven patients (25%), 2) complete subepicardial reentry circuits in four VTs (9%) and four patients (14%), 3) incompletely mapped circuits with a left ventricular endocardial breakthrough preceding the epicardial breakthrough in 25 VTs (53%) and 21 patients (75%), 4) incompletely mapped circuits with a left ventricular epicardial breakthrough preceding the endocardial breakthrough in three VTs (6%) and three patients (11%), and 5) a right ventricular epicardial breakthrough preceding the left ventricular endocardial breakthrough in eight VTs (17%) and seven patients (25%). After surgery, one type 3 VT and three type 5 VTs were reinducible. Thus, left ventricular endocardial reentry substrates (types 1 and 3) accounted for 68% of VTs, but substrates involving subepicardial (types 2 and 4) and deep septal layers (type 5) accounted for 32% of VTs. CONCLUSIONS: In a substantial number of VTs, a substrate localization that is at variance with the conventional concept can be detected by simultaneous epicardial and endocardial mapping and may require modification of the surgical approach conventionally aimed at endocardial layers. PMID- 1884440 TI - Regional three-dimensional geometry and function of left ventricles with fibrous aneurysms. A cine-computed tomography study. AB - BACKGROUND: To assess the extent and nature of the dysfunction surrounding aneurysms of the left ventricle (LV), we examined the parameters of local and global three-dimensional shape, size, and function of LVs of eight patients with histologically confirmed anterior fibrous aneurysms. METHODS AND RESULTS: Three dimensional reconstructions of each LV were made from 10-12 short-axis fast cine angiographic computed tomography (cine-CT) slices encompassing the entire heart at end diastole and end systole. Regional three-dimensional wall thickness, thickening, motion, curvature, and stress index were calculated for 84 elements encompassing the entire LV. The aneurysmal border was defined by a sharp decrease in end-diastolic wall thickness and separated the LV into an aneurysmal zone and a normal zone that was further divided into adjacent normal (AN) and remote normal (RN) zones. As expected, thickening was negligible in both the aneurysmal and the border zones. Although both the AN and the RN zones had normal wall thickness (1.05 +/- 0.20 and 1.09 +/- 0.20 cm, respectively), thickening was depressed in the AN (0.22 +/- 0.08 cm) but not the RN (0.44 +/- 0.19 cm) zones. The size of the dysfunction zone (defined as less than 2 mm thickening) was found to be considerably greater than the anatomic size of the aneurysm (60.9 +/- 13.7% versus 33.6 +/- 7.6% of the left ventricular endocardial area, respectively; p less than 0.001). In addition, the AN zone had a smaller curvature and a higher stress index than the RN zone. CONCLUSIONS: LVs with fibrous aneurysms are characterized by a relatively large region of nonfunction that encompasses the thin aneurysmal area and its transitional border zone, a normally functioning remote zone, and an intermediate region of normal wall thickness but with reduced function, which may be attributed to its low curvature and high stress index. PMID- 1884441 TI - Intravascular ultrasound assessment of lumen size and wall morphology in normal subjects and patients with coronary artery disease. AB - BACKGROUND: Necropsy studies demonstrate that coronary artery disease (CAD) is frequently complex and eccentric. However, angiography provides only a silhouette of the vessel lumen. Intravascular ultrasound is a new tomographic imaging method for evaluation of coronary dimensions and wall morphology. Few data exist regarding intravascular ultrasound in patients with CAD, and no data exist for subjects with normal coronaries. METHODS AND RESULTS: We used a multielement 5.5F, 20-MHz ultrasound catheter to examine eight normal subjects and 43 patients with CAD. We assessed the safety of coronary ultrasound and the effect of vessel eccentricity on comparison of minimum luminal diameter by angiography and ultrasound. Normal and atherosclerotic wall morphology and stenosis severity were also evaluated by intravascular ultrasound. The only untoward effect was transient coronary spasm in five patients. At 33 sites in normal subjects, the lumen was nearly circular, yielding a close correlation between angiographic and ultrasonic minimum diameter (r = 0.92). At 90 sites in patients with CAD, ultrasound demonstrated a concentric cross section; correlation was also close (r = 0.93). However, at 72 eccentric sites, correlation was not as close (r = 0.77). For 41 stenoses, correlation between angiography and ultrasound for area reduction was moderate (r = 0.63). In normal subjects, wall morphology revealed a thin (0.30 mm or less) intimal leading edge and subadjacent sonolucent zone (0.20 mm or less). Patients with CAD exhibited increased thickness and echogenicity of the leading edge, thickened sonolucent zones, and/or attenuation of ultrasound transmission. CONCLUSIONS: These data establish that intravascular ultrasound is feasible and safe and yields luminal measurements that correlate generally with angiography. Differences between angiographic and ultrasound measures of lumen size in eccentric vessels probably reflect the dissimilar perspectives of tomographic and silhouette imaging techniques. Intravascular ultrasound provides detailed images of normal and abnormal wall morphology not previously possible in vivo. PMID- 1884442 TI - Dipyridamole echocardiography test. A new tool for detecting jeopardized myocardium after thrombolytic therapy. AB - BACKGROUND: We wished to assess whether dipyridamole echocardiography test (DET) can detect jeopardized myocardium after thrombolytic therapy. METHODS AND RESULTS: Seventy-six consecutive patients with a first acute myocardial infarction (AMI) were treated with 2 million IU urokinase i.v. within 4 hours of the onset of AMI and underwent high-dose (as much as 0.84 mg/kg over 10 minutes) DET 8-10 days after AMI. The results were correlated to the anatomy of the infarct-related vessel (IRV). In patients with positive DET, we evaluated the wall motion score index (WMSI; a semiquantitative integrated estimation of extent and severity of the stress-induced dyssynergy). WMSI was derived by summation of individual segment scores divided by the number of interpreted segments. In a 13 segment model, each segment was assigned a score ranging from 1 (normal) to 4 (dyskinetic). Fifty-three patients had positive results on DET. Of these, 42 had dipyridamole-induced new wall motion abnormalities (WMAs) confined to the infarct zone or adjacent segments. In these patients, mean WMSI increased from 1.46 +/- 0.26 (at resting conditions) to 1.73 +/- 0.35 (at peak dipyridamole) (p less than 0.01), whereas no significant change was detected in negative patients (1.6 +/- 0.34 versus 1.57 +/- 0.34, p = NS). Coronary angiography showed a patent IRV (TIMI grade 2 or 3) in 53 patients and no or minimal reperfusion (TIMI grade 0 or 1) in 23 patients. A patent IRV with critical residual stenosis was found in 35 of 42 patients with dipyridamole-induced WMAs in the infarct zone and in 18 of 34 patients without WMAs (p less than 0.05). Among the 23 patients with occluded IRVs, nine had collateral flow to the distal vessel; six of these had a positive DET. Thus, the sensitivity and specificity for identifying a critically stenotic but patent IRV or the presence of a collateral-dependent zone were 66% and 93%, respectively. In a subset of nine patients with a positive DET in the infarct zone or adjacent segments, DET and a control coronary angiography were repeated 1 3 months after an angiographically successful (residual stenosis, 50% or less) coronary angioplasty in the IRV. The repeat DET was negative in eight patients (all with patent IRV at control angiography) and again positive in one patient, who showed restenosis at angiography. The WMSI, at resting conditions was similar before and after angioplasty, whereas it differed significantly at peak dipyridamole (1.7 +/- 0.2 versus 1.4 +/- 0.2, p less than 0.01). CONCLUSIONS: DET can identify the anatomy of the IRV, and dipyridamole-induced WMAs within the infarct zone detect regions with jeopardized myocardium that may benefit from intervention. PMID- 1884443 TI - Contrasting effects of digitalis and dobutamine on baroreflex sympathetic control in normal humans. AB - BACKGROUND: Digitalis glycosides augment cardiopulmonary baroreceptor mechanisms in animals. This could result from inotropic actions or from direct sensitization of cardiac mechanoreceptors. METHODS AND RESULTS: To determine if digitalis has similar actions in humans and to evaluate the mechanisms involved, we measured muscle sympathetic nerve activity (MSNA; microneurography) during unloading of cardiopulmonary baroreceptors with incremental lower body negative pressure (LBNP; 0 to -15 mm Hg) and during the cold pressor test in 22 normal subjects (age 22 +/- 1 year, mean +/- SEM). Arterial and central venous pressures, heart rate, and MSNA were measured during LBNP before and after intravenous digitalis (Cedilanid 0.02 ng/kg, n = 8), dobutamine (2.8 +/- 0.5 micrograms/kg/min, n = 8), or placebo (n = 6). Digitalis and dobutamine produced similar increases in baseline mean arterial pressure and decreases in central venous pressure and MSNA. LBNP produced similar decreases in central venous pressure in all groups before and after drug administration. The MSNA responses to LBNP were markedly potentiated by digitalis but not by dobutamine or placebo. CONCLUSIONS: Digitalis did not alter responses to the cold pressor test. Thus, digitalis selectively potentiated cardiopulmonary baroreflex regulation of sympathetic neural responses in normal humans, whereas dobutamine (another positive inotropic agent) did not produce this effect. We conclude that digitalis augments cardiopulmonary baroreflex control of sympathetic activity, probably by direct baroreceptor sensitization. PMID- 1884444 TI - The long QT syndrome. Prospective longitudinal study of 328 families. AB - BACKGROUND: The Long QT Syndrome (LQTS) is an infrequently occurring familial disorder in which affected individuals have electrocardiographic QT interval prolongation and a propensity to ventricular tachyarrhythmic syncope and sudden death. We prospectively investigated the clinical characteristics and the long term course of 3,343 individuals from 328 families in which one or more members were identified as affected with LQTS (QTc greater than 0.44 sec1/2). METHODS AND RESULTS: The first member of a family to be identified with LQTS, the proband, was usually brought to medical attention because of a syncopal episode during childhood or teenage years. Probands (n = 328) were younger at first contact (age 21 +/- 15 years), more likely to be female (69%), and had a higher frequency of preenrollment syncope or cardiac arrest with resuscitation (80%), congenital deafness (7%), a resting heart rate less than 60 beats/min (31%), QTc greater than or equal to 0.50 sec1/2 (52%), and a history of ventricular tachyarrhythmia (47%) than other affected (n = 688) and unaffected (n = 1,004) family members. Arrhythmogenic syncope often occurred in association with acute physical, emotional, or auditory arousal. The syncopal episodes were frequently misinterpreted as a seizure disorder. By age 12 years, 50% of the probands had experienced at least one syncopal episode or death. The rates of postenrollment syncope (one or more episodes) and probable LQTS-related death (before age 50 years) for probands (n = 235; average follow-up 54 months per patient) were 5.0% per year and 0.9% per year, respectively; these event rates were considerably higher than those observed among affected and unaffected family members. CONCLUSIONS: Among 232 probands and 1,264 family members with prospective follow up, three factors made significant independent contributions to the risk of subsequent syncope or probable LQTS-related death before age 50 years, whichever occurred first (Cox hazard ratio; 95% confidence limits): 1) QTc (1.052; 1.017, 1.088), 2) history of cardiac event (3.1; 1.3, 7.2), and 3) heart rate (1.017; 1.004, 1.031). The findings from this prospective longitudinal study highlight the clinical features, risk factors, and course of LQTS. PMID- 1884445 TI - Adenosine as a vasodilator in primary pulmonary hypertension. AB - BACKGROUND: The acute administration of vasodilator drugs to patients with primary pulmonary hypertension has been advocated to identify those with reversible pulmonary vasoconstriction. Unfortunately, the usefulness of the drugs currently available is limited by accompanying systemic hypotension. A vasodilator with effects confined to the pulmonary circulation would therefore be advantageous in such patients. METHODS AND RESULTS: The purine nucleoside adenosine was infused into the pulmonary artery in seven patients with primary pulmonary hypertension (baseline pulmonary vascular resistance [PVR], 442-1,295 dyne/cm/sec-5) to determine its effect on PVR. In all patients, there was a dose dependent and significant reduction (mean maximal percent decrease from baseline, 38.9%; p less than 0.001) in PVR mediated through a decrease in pulmonary artery pressure and an increase in cardiac output. Systemic vascular resistance (SVR) also decreased, but the ratio of PVR to SVR decreased (maximal mean percent decrease from baseline) by 10.5% (p less than 0.025), indicating that adenosine has a preferential vasodilator effect on the pulmonary circulation when administered in this manner. CONCLUSIONS: Because of its pharmacokinetic and vasodilator properties, adenosine may have a specific role in the investigation of primary pulmonary hypertension. PMID- 1884446 TI - Cerebral vasoconstriction during head-upright tilt-induced vasovagal syncope. A paradoxic and unexpected response. AB - BACKGROUND: To determine the effect of vasovagally mediated syncope on the cerebral circulation, transcranial Doppler sonography was used to assess changes in cerebral blood flow velocity during head-upright tilt-induced syncope. METHODS AND RESULTS: Thirty patients (17 men and 13 women; mean age, 43 +/- 22 years) with recurrent unexplained syncope were evaluated by use of an upright tilt-table test for 30 minutes, with or without an infusion of intravenous isoproterenol (1 4 micrograms/min), in an attempt to provoke bradycardia, hypotension, or both. Transcranial Doppler sonography was used to assess middle cerebral artery systolic velocity (Vs), diastolic velocity (Vd), ratio of systolic to diastolic velocities, pulsatility index (PI = Vs-Vd/Vmean), and resistance index (RI = Vs Vd/Vs) before, during, and after tilt. Syncope occurred in six patients (20%) during the baseline tilt and 14 (46%) during isoproterenol infusion (total positives, 66%). In the tilt-positive patients, concomitant with the development of hypotension and bradycardia, transcranial Doppler sonography showed a 75 +/- 17% decrease in diastolic velocity, unchanged systolic velocity, a 46 +/- 17% decrease in mean velocity, a 295 +/- 227% increase in pulsatility index, and a 73 +/- 34% increase in resistance index. CONCLUSIONS: These findings reflect increased cerebrovascular resistance secondary to arteriolar vasoconstriction distal to the insonation point of the middle cerebral artery. This is paradoxic because the expected response of the cerebral circulation to hypotension is vasodilation. We conclude that abnormal baroreceptor responses triggered during vasovagal syncope result in a derangement of cerebral autoregulation with paradoxic vasoconstriction in the face of increasing hypotension. PMID- 1884447 TI - Hyperinsulinemia, sex, and risk of atherosclerotic cardiovascular disease. AB - BACKGROUND: The possibility that hyperinsulinemia may be involved in the etiology of atherosclerotic cardiovascular disease (CVD) was first suggested 20 years ago. During the last decade, this possibility has received support from three large prospective studies. METHODS AND RESULTS: In the present study, the association between CVD, glucose intolerance, obesity, and hypertension (the GOH conditions) and hyperinsulinemia was examined cross-sectionally in a representative sample (n = 1,263) of the adult Jewish population aged 40-70 years in Israel. Previously known diabetics were excluded. CVD comprising clinical or ECG evidence of ischemic heart disease, as well as clinical evidence of cerebrovascular or peripheral vascular disease, was identified in 97 men and 39 women. A significant (p less than 0.01) hyperinsulinemia-sex interaction was found for CVD rate, with the adjusted risk ratios (followed by 95% confidence limits), relative to the rate in 298 normoinsulinemic women, being 1.15 (0.68-1.95) in 328 normoinsulinemic men, 0.85 (0.48-1.49) in 277 hyperinsulinemic women, and 2.27 (1.33-3.08) in 360 hyperinsulinemic men. Age-adjusted CVD rates in men versus women were: a) similar and low among all normoinsulinemic normotensives and hyperinsulinemics free of any of the GOH conditions (all rates less than or equal to 6.5%); b) similar and high among normoinsulinemic hypertensives (13.4% versus 10.4%); c) significantly higher in men among hyperinsulinemic normotensives with glucose intolerance and/or obesity (15.2% versus 3.3%; p = 0.02) and all hyperinsulinemic hypertensives (21.5% versus 12.8%; p = 0.04). These trends remained significant after adjusting for age, ethnic group, and blood lipids. CONCLUSIONS: Therefore, hyperinsulinemia was associated with excess CVD risk in men but not in women, and all excess CVD risk in men was confined to hyperinsulinemic individuals in the presence of glucose intolerance, obesity, or hypertension. PMID- 1884448 TI - Relation of risk factor levels in young adulthood to parental history of disease. The CARDIA study. AB - BACKGROUND: The relation between self-reported parental disease and risk factor levels was examined in 2,637 black and 2,478 white men and women aged 18-30 years at the Coronary Artery Risk Development in Young Adults (CARDIA) Study baseline examination (1985-1986). METHODS AND RESULTS: The prevalence of parental disease (at least one parent) in white versus black participants was 44% and 56% for hypertension, 47% and 44% for obesity, 16% and 13% for myocardial infarction, 11% and 17% for diabetes, and 6% and 10% for stroke, respectively. Among these young adults, parental hypertension was associated with higher sex- and age-adjusted systolic and diastolic blood pressure levels. Parental myocardial infarction was associated with higher plasma cholesterol, higher blood pressure levels, and lower high density lipoprotein cholesterol levels in white participants. Parental diabetes was associated with higher fasting blood glucose and insulin levels in all race-sex groups and with higher triglycerides and lower high density lipoprotein cholesterol in black participants only. Parental history of obesity was related to less favorable age- and sex-adjusted lipid levels in white participants and higher blood pressure levels in black participants. Parental history of stroke was associated with higher systolic blood pressure levels in black participants. In general, these differences across family history were predicted only in part by obesity. The prevalence of more than one disease reported in parents occurred more frequently than would have been expected due to chance alone. CONCLUSIONS: These associations between parental disease and risk factors in their adult children probably reflects the impact of both environmental and genetic factors. Parental history may be a useful marker for high risk individuals. PMID- 1884449 TI - Anomalous insertion of papillary muscle directly into anterior mitral leaflet in hypertrophic cardiomyopathy. Significance in producing left ventricular outflow obstruction. AB - BACKGROUND: Obstruction to left ventricular outflow in hypertrophic cardiomyopathy (HCM) is usually due to systolic anterior motion of the mitral valve. Occurrence of structural mitral valve abnormalities in HCM and their significance in producing outflow obstruction (even in the absence of typical systolic anterior motion) has not been fully appreciated. METHODS AND RESULTS: Analysis of 78 mitral valves excised from patients with obstructive HCM showed that 10 (13%) had anomalous insertion of one or both left ventricular papillary muscles directly into the anterior mitral leaflet. This malformation was identified by echocardiography, which demonstrated direct continuity between the hypertrophied papillary muscle and mitral leaflet, resulting in a long rigid area of midcavity narrowing that appeared to be solely or largely responsible for outflow obstruction. Basal subaortic pressure gradients were large (70-150 mm Hg). Mitral valve replacement reduced the outflow gradient substantially to 0-15 mm Hg in four patients with postoperative cardiac catheterization. However, two other patients who underwent septal myotomy/myectomy had persistent symptoms and incomplete relief of obstruction (gradients 60 and 70 mm Hg) because of continued midcavity apposition of papillary muscle and ventricular septum. CONCLUSIONS: Anomalous papillary muscle insertion into anterior mitral leaflet represents a mechanism of obstruction to left ventricular outflow in patients with HCM and differs considerably from typical dynamic obstruction caused by mitral valve systolic anterior motion that occurs in many other patients with HCM. Recognition of this malformation emphasizes the diverse morphological expression of HCM and also has important clinical implications for patients requiring operation because the gradient is likely to persist even after adequate myotomy/myectomy; consequently, mitral valve replacement would appear to be the operation of choice in most such patients. PMID- 1884450 TI - Dobutamine increases cardiac output of the total artificial heart. Implications for vascular contribution of inotropic agents to augmented ventricular function. AB - BACKGROUND: The synthetic catecholamine dobutamine increases stroke volume in normal subjects and in patients with congestive heart failure. In addition to its direct influence on myocardial contractility, dobutamine may significantly modulate vascular tone because of its alpha- and beta-adrenergic agonist activity. METHODS AND RESULTS: To test the hypothesis that such vasoactive properties significantly contribute to the improved ventricular performance noted with this agent, hemodynamic parameters were measured during stepped ascension infusion of dobutamine in a model that is insensitive to positive inotropic stimulation. Administration of dobutamine in nine calves that underwent replacement of the native right and left ventricles with pneumatically driven total artificial hearts resulted in a significant (p = 0.0001) increase in cardiac output from 7.0 +/- 1.8 to 8.2 +/- 1.8 l/min and a significant (p = 0.0001) decrease in total peripheral vascular resistance from 1,224 +/- 559 to 745 +/- 317 dyne.sec/cm5. A less marked influence was noted on the pulmonary vasculature, with pulmonary vascular resistance exhibiting a significant (p less than 0.05) decrease from its baseline value only at the peak infusion. Consistent with an increase in venous return, both left and right atrial pressures increased significantly (p less than 0.005) with dobutamine administration. CONCLUSIONS: These data demonstrate that the vasoactive properties of dobutamine significantly contribute to improved ventricular performance independent of direct myocardial stimulation. This effect appears to result in part from a direct modulation of myocardial stimulation. This effect appears to result in part from a direct modulation of arterial and venous tones rather than from a reflex response to primary changes in contractility. PMID- 1884451 TI - Early detection of rejection and assessment of cyclosporine therapy by 111In antimyosin imaging in mouse heart allografts. AB - BACKGROUND. Mice (n = 58) with abdominal heterotopic heart transplants were studied to examine the effectiveness of 111In-labeled antimyosin scintigraphy in the detection of rejection and to determine the consequence of cyclosporine therapy on the results. METHODS AND RESULTS. Allografts from B10D2 donors were transplanted into B6AF1 recipients. Of the 49 allografted mice, 19 were treated with cyclosporine (15 mg/kg.day). Nine isografted mice served as controls. Scintigraphy was performed by injecting 100 muCi 111In antimyosin monoclonal antibody 2-15 days after transplantation. An increase in the ratio of percent dose of antimyosin injected per gram (% dose/g) of the grafted heart (G) to that of the autologous heart (A) (G/A) as well as the increasing percent dose per gram of antimyosin in the grafts reflected the severity of histopathological rejection regardless of the presence or absence of cyclosporine. Scintigraphic images demonstrated unequivocally intense accumulation of 111In in rejected allografts as confirmed by histologically demonstrable myocyte necrosis. The G/A ratio in allografted mice with mildly deteriorated mechanical activity (4.2 +/- 1.0, mean +/- SD) was greater than that in mice with normal contractility (1.8 +/- 0.7) (p less than 0.001), and the necrosis correlated with this modest decline in mechanical function could be scintigraphically identified. Of mice with normally contracting allografts, the G/A ratio was greater in animals with demonstrated myocyte necrosis (2.6 +/- 0.5) than in those without necrosis (1.5 +/- 0.5) (p less than 0.001). In contrast, isografted mice or a subset of allografted mice treated with cyclosporine and not showing evidence of rejection did not manifest any significant change in G/A ratio, nor did they have scintigrams positive for rejection as late as 15 days after transplantation. CONCLUSIONS. These findings suggest that antimyosin scintigraphy is a sensitive and early indicator of cardiac transplant rejection and that it could be useful as a noninvasive method for assessing the efficacy of cyclosporine treatment. PMID- 1884452 TI - Loss of flow-mediated endothelium-dependent dilation occurs early in the development of atherosclerosis. AB - BACKGROUND: Healthy arteries exhibit endothelium-dependent dilation in response to both local acetylcholine and increased blood flow. In humans, clinically overt coronary artery disease is characterized by loss of dilation to both acetylcholine and blood flow. The temporal relation, however, between functional abnormalities of the endothelium and the development of atherosclerosis has not been established. METHODS AND RESULTS: We examined endothelial vasodilator function in vivo at an early stage of the development of atherosclerosis. Two groups of seven Macaca fascicularis monkeys were studied; one group was fed a high cholesterol diet (0.73-1.0 mg cholesterol per calorie) for 11 months. Cholesterol feeding was associated with increased plasma cholesterol levels and with intimal thickening of the iliac arteries but with no reduction in luminal diameter. Endothelium-dependent vasomotor responses of the iliac arteries were then examined in vivo by quantitative contrast angiography. Acetylcholine produced significant dilation in the controls but paradoxical constriction in the group with early atherosclerosis (+9.0 +/- 3.2% versus -5.3 +/- 5.4%, p less than 0.05). In response to a twofold increase in blood flow achieved by administering adenosine distal to the arterial segment under examination, the controls again dilated, whereas the atherosclerotic group failed to dilate (+ 11.6 +/- 2.1% versus + 0.5 +/- 2.4%, p less than 0.05). Both groups, however, were able to dilate, and dilated equally, to the nonendothelium-dependent agent nitroglycerin (+ 13.7 +/- 4.8% versus + 19.1 +/- 4.3%, NS). CONCLUSIONS: Endothelium-dependent vasodilation in response to both acetylcholine and increased blood flow may be lost early in the course of developing atherosclerosis before the appearance of stenosing and occlusive disease. PMID- 1884453 TI - Relation of early hemodynamic changes to final cardiac phenotype and survival after neural crest ablation in chick embryos. AB - BACKGROUND: Microcinephotography was used to study a model of persistent truncus arteriosus created in chick embryos by ablation of premigratory neural crest destined for the third and fourth aortic arch arteries as well as the septum of the cardiac outflow tract. METHODS AND RESULTS: Twenty-five control embryos and 105 of 202 experimental embryos were filmed on day 3 of incubation and then reincubated. The remaining 97 experimental embryos were not filmed because of twisting of the embryos, but they were reincubated. There was no difference in either the survival rate (p greater than 0.23) from day 3 to day 11 of incubation or the incidence of persistent truncus arteriosus (p greater than 0.08) between the filmed and the nonfilmed embryos. Incomplete looping of the cardiac tube observed in experimental embryos during early cardiogenesis correlated with a right ventricular origin of the outflow vessels in the definitive heart. Hemodynamic measurements indicated that there was no difference in heart rate, ejection fraction, systolic and diastolic areas, stroke volume, and cardiac output between controls and the experimental group as a whole. However, embryos that did not survive to day 11 had decreased stroke volume (p less than 0.001) and cardiac output (p less than 0.001), whereas embryos that survived to day 11 with cardiac malformations had increased stroke volume and cardiac output in early embryogenesis. CONCLUSIONS: Increased stroke volume and cardiac output may be necessary factors for survival in embryos with cardiac dysmorphogenesis and probably are associated with dilation of the ventricular portion of the cardiac tube, which leads to malalignment of the outflow vessel or vessels. PMID- 1884454 TI - Differential effects of heptanol, potassium, and tetrodotoxin on reentrant ventricular tachycardia around a fixed obstacle in anisotropic myocardium. AB - BACKGROUND: The aim of this study was to test the hypothesis that electrical uncoupling and depression of the fast sodium channels have differential effects on propagation of the electrical impulse relative to the fiber orientation. METHODS AND RESULTS: In a model of reentrant ventricular tachycardia (VT) (mean cycle length, 144 +/- 13 msec) around a ring of anisotropic myocardium in 10 Langendorff-perfused rabbit hearts, the effects of extracellular K+ concentration [( K+]o) and heptanol were studied. [K+]o and heptanol each had a dose-dependent effect on VT cycle length. However, high [K+]o slowed the VT mainly by depressing longitudinal conduction, whereas heptanol preferentially depressed transverse conduction. The ratio between longitudinal and transverse conduction velocities progressively decreased with high [K+]o and progressively increased with heptanol. Heptanol terminated VT at a mean concentration of 3.5 +/- 0.5 mM. The cycle length before termination was 446 +/- 120 msec (p less than 0.001). In eight of 10 experiments, termination occurred by failure of conduction during transverse propagation. VT terminated at a mean [K+]o of 11.6 +/- 1.8 mM. The cycle length before termination was 493 +/- 341 msec (p less than 0.01). In seven of 10 cases, termination occurred by failure of conduction during longitudinal propagation. In the remaining five episodes (two with heptanol and three with high [K+]o), termination occurred by collision of the reentrant beat with an antidromic impulse being reflected within the ring. In a separate series of six hearts, tetrodotoxin was administered during VT. Like high [K+]o, tetrodotoxin prolonged the cycle length of the VT by preferentially slowing longitudinal conduction, and VT was terminated by longitudinal block. CONCLUSIONS: During reentrant VT, electrical uncoupling of cells by heptanol or modification of active membrane properties by high [K+]o or tetrodotoxin has a differential depressing effect on propagation of the impulse relative to the fiber orientation. PMID- 1884455 TI - Localization of breakthrough site of canine monomorphic ventricular tachycardia by pacemapping. A vectorial approach. AB - BACKGROUND: The precision and limitations of ventricular pacemapping as a method to localize the site of earliest breakthrough of ventricular tachycardia (VT) were investigated in a canine model of experimental myocardial infarction. METHODS AND RESULTS: Forty-one episodes of VT induced in 10 animals were mapped using a standard grid of 64 endocardial and epicardial bipolar electrodes to determine the site of earliest endocardial or epicardial breakthrough of activation during VT. Each of these 64 recording sites was also used for ventricular pacing during sinus rhythm at cycle lengths comparable to those of the VTs. Orthogonal X, Y, and Z Frank electrocardiographic (ECG) leads were recorded during all episodes of VT and ventricular pacing from all sites after the chest was closed in all animals. Surface ECG waveforms corresponding to each VT and each ventricular pacing were compared pairwise by measuring the Euclidean metric difference between the VT and ventricular pacing vectors with the orthogonal ECG leads as their X, Y, and Z components. The pacing site that generated the vector most similar to VT vector (smallest vectorial difference) was defined as the predicted breakthrough site. This predicted site of breakthrough was identical to the actual site of breakthrough determined by activation sequence mapping during VT for only nine VTs (22%). However, for an additional 27 VTs (66%), the observed and predicted breakthrough locations were at adjacent (1 cm or less apart) recording sites. For five VTs (12%), the two sites were remote, the distance between them exceeding 1 cm. CONCLUSIONS: In this model, locating the breakthrough site by pacemapping is exact in only a small minority of VTs. However, when orthogonal surface ECG leads are used for comparison, pacemapping can predict the site of earliest breakthrough during VT with a 1-cm resolution in the majority of VTs. PMID- 1884456 TI - Repolarization inhomogeneities in ventricular myocardium change dynamically with abrupt cycle length shortening. AB - BACKGROUND: In single heart cells, abrupt changes in stimulation rate elicit complex alterations in repolarization. The effects of rate change on dispersion of repolarization, however, have not been well characterized. METHODS AND RESULTS: To determine the effects of abrupt cycle length (CL) shortening on spatial inhomogeneity of repolarization in a syncytium of ventricular cells, 124 action potentials were simultaneously recorded from Langendorff-perfused guinea pig hearts using high-resolution optical mapping with voltage-sensitive dye. The distribution of ventricular action potential durations (APDs) mapped during each cardiac cycle was used to calculate mean APD and repolarization dispersion index (DI), defined as the variance of the distribution. After abruptly shortening CL from 500 to 300 msec, mean APD declined exponentially in normoxic controls (by 23 +/- 3 msec, p less than 0.0001). This response was characterized by beat-to-beat oscillations of APD that were synchronized at all ventricular sites. After 30 minutes of hypoxia, mean APD decreased from 175.0 +/- 13.3 to 76 +/- 25.7 msec. However, during hypoxia, abrupt CL shortening lowered mean APD by only an additional 6 +/- 6 msec, and APD oscillations were no longer synchronized throughout the ventricle. In controls, beat-to-beat DI decreased significantly ( 51.0 +/- 6.8%, p less than 0.01) by the sixth post-CL shortening beat and then recovered (by 15-20 beats). In contrast, DI failed to decrease during hypoxia (+7.1 +/- 23%). Two mechanisms for the transient decline of DI in controls were identified: synchronous APD oscillations and transient diminution of the apical to-basal ventricular APD gradient. CONCLUSIONS: These data demonstrate that inhomogeneity of ventricular repolarization, as measured by DI, changes dynamically with CL shortening. Furthermore, the hypoxic ventricle does not attenuate DI after abrupt CL shortening and thereby lacks a physiological response expected to diminish vulnerability to arrhythmias. PMID- 1884457 TI - Effect of altered activation sequence on epicardial QRST area and refractory period in dogs. AB - BACKGROUND: We investigated the effects of activation sequence on cardiac surface QRST areas and refractory periods in experiments on dogs. METHODS AND RESULTS: Right and left ventricular pacings were performed, and the pacing site was altered every 6 minutes. After 4 minutes of a given pacing, 54 unipolar electrograms distributed over the entire cardiac surface were recorded. Next, refractory periods at electrode sites near pacing electrodes were measured. Paired right ventricular/left ventricular (RV/LV) pacing data were obtained six or seven times in each sample. Although the QRST isoarea maps during the two activation orders were qualitatively similar, it was recognized consistently from the right ventricle-left ventricle difference map that leads around the RV free wall had positive values and that leads around the LV free wall and apex had negative values. Compared with the same leads at RV and LV pacing, QRST areas were larger when pacing sites were near the leads. The local QRST areas of individual leads at which we measured local refractory period were consistently larger during drive from proximal pacing sites than during drive from distant pacing sites. Refractory periods were consistently longer during proximal pacing than during distal pacing, and there was a positive correlation between change in local QRST area and change in refractory period (r = 0.64) during altered activation sequence, whereas there was an inverse correlation between change in QRST area and change in refractory period (r = -0.91) during localized myocardial warming. CONCLUSIONS: Both local QRST areas and local refractory periods were dependent on the activation sequence, and there was a positive correlation between QRST areas and refractory periods during various activation sequences compared with localized myocardial warming. PMID- 1884458 TI - Neuronal reuptake of norepinephrine and production of dihydroxyphenylglycol by cardiac sympathetic nerves in the anesthetized dog. AB - BACKGROUND: Reuptake of norepinephrine by cardiac sympathetic nerves before and during two levels of electrical stimulation of the left ansa subclavia was estimated in anesthetized dogs from the cardiac production of dihydroxyphenylglycol (DHPG), the intraneuronal metabolite of norepinephrine. METHODS AND RESULTS: The method depended on the effects of neuronal uptake blockade with desipramine on the cardiac production of [3H]DHPG from intravenously infused [3H]norepinephrine. The ratio of the desipramine-induced decrease in the cardiac extraction of [3H]norepinephrine to the production of [3H]DHPG was used to transform the cardiac production of DHPG from recaptured norepinephrine into a rate for norepinephrine reuptake. Cardiac spillover of norepinephrine into plasma increased from 49 +/- 12 to 205 +/- 40 and 451 +/- 118 pmol/min during sympathetic activation. Cardiac DHPG production increased from 108 +/- 18 to 166 +/- 34 and 240 +/- 47 pmol/min. Desipramine decreased resting cardiac DHPG production by 20% and completely blocked the stimulation-induced increase. Thus, most (80%) cardiac DHPG produced at rest was derived from norepinephrine leaking from storage vesicles. This amount remained constant, and that derived from recaptured norepinephrine increased during sympathetic activation. The cardiac extraction of [3H]norepinephrine (126,000 dpm/min) and production of [3H]DHPG (3,790 dpm/min) were decreased by 55-57% after desipramine. Thus, only 3% of the norepinephrine recaptured by cardiac sympathetic nerves appeared in plasma as DHPG. The remainder was sequestered into storage vesicles (more than 94%) or ultimately formed metabolites other than DHPG (less than 3%). Reuptake of norepinephrine by cardiac sympathetic nerves was 1,188 +/- 476 pmol/min and increased in parallel with cardiac norepinephrine spillover to 4,182 +/- 1,982 and 6,594 +/- 2,241 pmol/min during sympathetic stimulation. CONCLUSIONS: Of the norepinephrine released by cardiac sympathetic nerves, 16-fold more was recaptured than entered plasma. Combined estimation of norepinephrine reuptake and spillover offers an approach to assess the efficiency of neuronal reuptake in disorders of cardiac function. PMID- 1884459 TI - Effects of an increase in intracellular free [Mg2+] after myocardial stunning on sarcoplasmic reticulum Ca2+ transport. AB - BACKGROUND: Myocardial stunning has been associated with a greater than twofold increase in intracellular free [Mg2+] from 0.6 to 1.5 mM. The effect of this increase in free [Mg2+] on the function of the sarcoplasmic reticulum (SR) Ca2+ pump was assessed in SR isolated from Langendorff perfused, isovolumic rabbit hearts after 15 minutes of global ischemia. METHODS AND RESULTS: Our results indicate that myocardial stunning results in a shift in the Ca2+ sensitivity of oxalate-supported, Ca2+ transport over the entire range of free [Ca2+] associated with the cardiac cycle. Using 0.6 mM free Mg2+ as control, maximal rates of Ca2+ transport occurred at 1 microM free Ca2+ (control, 519 +/- 32; stunned, 337 +/- 37 nmol Ca2+.min-1.mg-1). At 0.56 microM free Ca2+, SR Ca2+ transport was reduced from a control of 351 +/- 49 to 263 +/- 12 nmol Ca2+.min-1.mg-1 at 0.6 mM free [Mg2+]. Moreover, an increase in the free [Mg2+] from 0.6 to 1.5 mM results in a greater shift in the Ca2+ activation curve with no change in the level of maximal activation. Ca2+ transport at 0.56 microM free Ca2+ was shifted in the stunned SR from 263 +/- 12 to 138 +/- 29 nmol Ca2+.min-1.mg-1 at 0.6 and 1.5 mM free Mg2+, respectively. CONCLUSIONS: These results indicate that an increase in free [Mg2+] after stunning in combination with the inherent defect in the SR Ca2+ ATPase may reduce the ability of the cell to regulate Ca2+ to a greater extent than previously observed. This impairment in Ca2+ regulatory function may contribute directly to the increase in diastolic tone and indirectly to the reduced systolic function characteristic of the stunned myocardium. PMID- 1884461 TI - Introduction to Ancel Keys Lecture. Ancel Keys, pioneer. PMID- 1884462 TI - Ancel Keys Lecture. PMID- 1884460 TI - Effects of dietary omega 3 fatty acids on vascular contractility in preanoxic and postanoxic aortic rings. AB - BACKGROUND: Vasomotor reactivity may contribute to the pathophysiology of ischemic injury. The atherosclerotic vessel may be particularly susceptible to vasoconstriction because of the damaged endothelial layer with resultant loss of vasodilatory factors. While dietary omega 3 fatty acids have been proposed to protect against vascular occlusion, it is not clear to what extent this results from alterations in the function of platelets or from changes intrinsic to the blood vessel itself. METHODS AND RESULTS: The effects of dietary supplementation with fish oils on vascular contractility were examined in endothelialized and de endothelialized aortic rings under pre- and postanoxic conditions. De endothelialization was defined functionally by the loss of acetylcholine-induced vasodilation in norepinephrine-preconstricted aortic rings from rats fed normal rat chow. Three groups of rats were fed diets containing either 20% menhaden oil or 20% beef tallow, both supplemented with 3% corn oil or 23% corn oil for longer than 4 weeks. All animals received vitamin E. Under well-oxygenated conditions, de-endothelialized aortic rings from rats fed fish oil and corn oil contracted to similar extents with norepinephrine and vasopressin and less than rings from rats fed beef tallow. Endothelialized (intact) and de-endothelialized rings from rats fed fish oil relaxed more in response to acetylcholine than rings from rats fed beef tallow and corn oil. After anoxic exposure and reoxygenation, KCl-induced contraction of intact rings from rats fed fish oil and corn oil was similar and less than rings from rats fed beef tallow. Intact and de-endothelialized rings from rats fed fish oil relaxed more to acetylcholine than did rings from rats fed beef tallow and corn oil. CONCLUSIONS: Under preanoxic or postanoxic conditions, rings from rats fed fish oil and corn oil contracted less than rings from rats fed beef tallow. The relaxation response to acetylcholine, however, was greater in rings from rats fed fish oil than from rats fed either corn oil or beef tallow. These vascular effects of fish oil feeding may result in increased blood flow to ischemic and reperfused tissues in vivo. PMID- 1884463 TI - A lesson from the controversy about heart rate adjustment of ST segment depression. AB - To summarize the literature review, the heart rate adjustment appears to be able to perfectly discriminate patients with different numbers of diseased coronary vessels in one center, to increase the diagnostic accuracy of three-vessel or left main disease in eight centers, and unable to improve accuracy in seven centers. To explain those differences, several methodological and statistical biases have been considered. However, a recent report regarding the application of the method in eight centers and a meticulous literature review could not explain the superior performance in some laboratories. PMID- 1884464 TI - Antioxidants and atherosclerosis. A current assessment. PMID- 1884465 TI - Clinical trials of restenosis after coronary angioplasty. PMID- 1884466 TI - Adenosine and selective reduction of pulmonary vascular resistance in primary pulmonary hypertension. PMID- 1884467 TI - Insulin. A sex hormone for cardiovascular risk? PMID- 1884468 TI - A family history of risk factors and cardiovascular diseases. PMID- 1884469 TI - Anisotropic structural complexities in the genesis of reentrant arrhythmias. PMID- 1884470 TI - Editorial comment: Endothelin: key to coronary vasospasm? PMID- 1884471 TI - Point of view: use of left ventricular function as prognostic factor. PMID- 1884472 TI - Consequences of reocclusion after successful reperfusion therapy in acute myocardial infarction. PMID- 1884473 TI - Echocardiographic Doppler evaluation of left ventricular diastolic function. Physics and physiology. PMID- 1884474 TI - Structure, function, and regulation of troponin C. PMID- 1884475 TI - Diagnostic accuracy of thallium-201 myocardial perfusion imaging. AB - Myocardial thallium-201 (Tl-201) imaging performed in conjunction with exercise stress has enhanced the accuracy of detecting coronary artery disease among patients with chest pain. Sensitivity and specificity of qualitative visual Tl 201 scintigraphy for detection of coronary artery disease average 84% and 87%, respectively. Quantitative analysis of planar Tl-201 scintigrams has yielded sensitivity and specificity in the 90% range. Single photon emission computed tomographic imaging is associated with even higher sensitivity but with specificity in the 82-85% range. Perfusion defects representing ischemia can now be distinguished from scar by demonstration of delayed Tl-201 redistribution or enhanced uptake after reinjection of a second dose of Tl-201. Stenoses of the left circumflex coronary artery are less easily detected than lesions of the right and left anterior descending coronary arteries. False-positive Tl-201 perfusion defects may occur as a result of attenuation artifacts, most often caused by overlying breast tissue or by a high left hemidiaphragm. Patient motion during acquisition of single photon emission computed tomographic images results in artifactual defects on reconstruction. Abnormal Tl-201 uptake has been noted in patients with 1) left bundle branch block and normal coronary arteries, 2) hypertrophic cardiomyopathy, and 3) progressive systemic sclerosis. PMID- 1884476 TI - Radionuclide assessment of infarct size and left ventricular function in clinical trials of thrombolysis. AB - Mortality, left ventricular ejection fraction, and infarct size are important end points in evaluating the efficiency of thrombolytic treatment in clinical trials. Radionuclide assessment of ejection fraction and infarct size is safe, accurate, reproducible, and readily available. Its use in clinical trials supplements mortality data and allows meaningful results in trials with smaller patient numbers. Single photon emission computed tomography improves the detection and quantification of infarct size, and its use with new radiopharmaceuticals will assume an important role in future trials. For an 8-year period, these radionuclide techniques have been used in the Western Washington Thrombolysis Trials and have generally shown smaller infarct size and higher ejection fractions in patients receiving streptokinase and tissue-type plasminogen activator. However, in the most recent trial there was no direct relation between these end points and the time between symptom onset and initiation of treatment. Future trials that direct efforts to treatment in the first hour after symptom onset should further clarify this observation. PMID- 1884477 TI - The role of echocardiography in the evaluation of mechanical complications of acute myocardial infarction. AB - With the introduction of the coronary care unit and more effective therapy for primary life-threatening arrhythmias, cardiogenic shock and the mechanical complications of acute myocardial infarction are now responsible for the majority of in-hospital deaths. These mechanical complications, which include myocardial rupture of the left ventricular free wall, rupture of the ventricular septum, and rupture of the papillary muscle, are estimated to account for 25,000 fatalities yearly in the United States. Although the mechanism of myocardial rupture has not been clearly defined, there is increasing evidence that infarct expansion, which can be readily detected by two-dimensional echocardiography, may be an important pathophysiologic factor. The ready availability of echocardiography in the coronary care unit has made a major impact on the immediate diagnosis of mechanical complications in the hemodynamically compromised patient with acute myocardial infarction. In particular, two-dimensional and Doppler echocardiographic techniques have been extremely useful in the identification and localization of ventricular septal rupture. In addition, papillary muscle rupture can be readily diagnosed by Doppler approaches and is easily distinguished from ventricular septal rupture. In view of increasing evidence that early surgical intervention is indicated in these patients, these echocardiographic approaches offer the surgeon prompt diagnostic and anatomic information. Unfortunately, rupture of the free wall of the left ventricle often results in sudden death within minutes before echocardiographic evaluation can be attempted. Nevertheless, rapid echocardiographic diagnosis provides the patient with the possibility of potential life-saving resuscitative interventions before immediate surgery. Thus, over the past decade, echocardiography has become a vital tool in the diagnosis and evaluation of patients with mechanical complications of acute myocardial infarction. The development of Doppler techniques, color flow Doppler, and esophageal approaches should further enhance our diagnostic abilities and allow careful monitoring of patients before, during, and after surgical repair. It is hoped that with the improvements in echocardiographic evaluation of mechanical rupture and more rapid surgical intervention, future studies will demonstrate better surgical results with good long-term survival in patients with myocardial rupture. PMID- 1884478 TI - Positron emission tomography for the assessment of myocardial viability. AB - The detection of viable myocardium or ischemically injured myocardium with a reversible impairment of contractile function remains clinically important but challenging. Detection of reversible dysfunction and distinction from irreversible tissue injury by positron emission tomography is based on identification of preserved or even enhanced glucose metabolism with F-18 2 fluoro 2-deoxyglucose. Regional patterns of myocardial glucose utilization and blood flow, defined as perfusion-metabolism mismatches or matches, on positron emission tomography in patients with chronic or even acute ischemic heart disease are highly accurate in predicting the functional outcome after interventional revascularization. Compared with thallium-201 redistribution scintigraphy, positron emission tomography appears to be diagnostically more accurate, especially in patients with severely impaired left ventricular function. While larger clinical trials are needed for further confirmation, positron emission tomography has already proved clinically useful for stratifying patients with poor left ventricular function to the most appropriate therapeutic approach. PMID- 1884479 TI - Dipyridamole 201Tl scintigraphy in the evaluation of prognosis after myocardial infarction. AB - Dipyridamole 201Tl imaging has been proposed as an alternative to exercise ECG testing for the prehospital discharge evaluation of patients recovering from myocardial infarction. The rationale is that many postinfarction patients with exercise-induced ischemia experience later cardiac events, and the sensitivity of predischarge exercise ECG testing in patients with multivessel disease ranges from only 45% to 62%. In addition, several groups of investigators have shown the sensitivity of submaximum exercise 201Tl imaging to be less than ideal. This report summarizes the current status of dipyridamole 201Tl imaging in the period of 1-13 days after myocardial infarction. Although the number of studies performed to date is limited, the following conclusions can be drawn: dipyridamole 201Tl imaging after myocardial infarction was associated with no serious side effects, and those present could be quickly reversed with aminophylline; redistribution with dipyridamole 201Tl images definitely correlates with prognosis after uncomplicated myocardial infarction; dipyridamole 201Tl imaging is definitely useful in patients unable to exercise for a variety of reasons; and future studies are definitely indicated to further define the role of dipyridamole 201Tl imaging for assessing prognosis, especially in those patients undergoing interventional therapy after acute myocardial infarction. PMID- 1884480 TI - Value of planar 201Tl imaging in risk stratification of patients recovering from acute myocardial infarction. AB - Although exercise ECG testing has been shown to have important prognostic value after acute myocardial infarction, exercise 201Tl scintigraphy offers several potential advantages, including: 1) increased sensitivity for detecting residual myocardial ischemia; 2) the ability to localize ischemia to a specific area or areas subtended by a specific coronary artery; 3) the ability to identify exercise-induced left ventricular dysfunction, which is manifested by increased lung uptake or transient left ventricular dilation; and 4) more reliable risk stratification of individual patients. The more optimal prognostic efficiency of 201Tl scintigraphy partially results from the fact that the error rate in falsely classifying patients as low risk is significantly smaller with 201Tl scintigraphy than with stress ECG. Because of these substantial advantages, there seems to be adequate rationale for recommending exercise perfusion imaging rather than exercise ECG alone as the preferred method for evaluating mortality and morbidity risks after acute myocardial infarction. PMID- 1884481 TI - Risk stratification after myocardial infarction with exercise and Doppler echocardiography. AB - Exercise testing early after myocardial infarction has been shown to be of further risk stratification value among otherwise low-risk patients on the basis of an uncomplicated clinical course. The addition of cardiac imaging modalities to exercise testing has augmented this capacity. Exercise echocardiographic imaging before and immediately after treadmill exercise can be accomplished in 85 95% of patients. New or worsening wall motion abnormalities identify 63-80% of patients who will suffer cardiac events and correctly predict 78-95% of those who will not. In addition, exercise echocardiography can detect multivessel coronary artery disease with a sensitivity of 80% and a specificity of 90%. These results are superior to those obtained by analyzing global left ventricular function during exercise, exercise aortic Doppler velocity profiles, or exercise electrocardiography. How exercise echocardiography compares with 201Tl perfusion imaging after myocardial infarction awaits a systematic study. Therefore, the choice between exercise echocardiography and perfusion imaging depends on physician preference, availability, cost, and service. PMID- 1884482 TI - Radionuclide assessment of ventricular function and risk stratification after myocardial infarction. AB - Prognosis after acute myocardial infarction is determined primarily by left ventricular function and by the extent to which additional coronary obstructions jeopardize viable myocardium. Radionuclide ventriculography is well suited for noninvasive assessments of resting and exercise ventricular function after acute myocardial infarction. The prognostic importance of resting left ventricular function after acute myocardial infarction is well established. Several studies have reported the prognostic utility of submaximal exercise radionuclide ventriculography at the time of hospital discharge. Patients with globally depressed left ventricular function after acute myocardial infarction are at increased risk for cardiac death, while patients with normal resting ventricular function but abnormal function during exercise appear to be at risk for nonfatal ischemic events. The development of gated tomographic techniques and new radiopharmaceuticals will make available more accurate and detailed assessments of ventricular function and combined assessments of function and perfusion. These new developments require further investigation but appear to be promising new techniques with the potential for providing improved assessments of prognosis after acute myocardial infarction. PMID- 1884483 TI - Risk stratification after myocardial infarction. Clinical overview. AB - Many patients with an acute myocardial infarction can be stratified into subgroups that are at high risk for morbidity and mortality on the basis of clinical characteristics that indicate recurrent myocardial ischemia, persistent left ventricular dysfunction, and/or recurrent cardiac arrhythmias. In patients with uncomplicated myocardial infarction the assessment of symptoms, physical findings, and ECG changes during predischarge exercise testing often identifies patients at increased risk for further cardiac events. Because of the suboptimum sensitivity and specificity of the exercise ECG for detecting myocardial ischemia, myocardial perfusion imaging with 201Tl and/or assessment of global and segmental ventricular function by two-dimensional echocardiography or radionuclide cineangiography during or immediately after exercise are often added to the predischarge risk stratification. PMID- 1884484 TI - Assessment of aortic and pulmonic stenosis by echocardiography. AB - Doppler and imaging echocardiography are highly useful methods of identifying and quantifying both aortic and pulmonic stenosis. The presence of valve stenosis and associated regurgitation is based on detecting abnormal intracardiac velocity patterns near the affected valve. Defining the specific valve involved and the type of lesion present is based on determining the location and timing of the abnormal velocities. Both color flow imaging and duplex pulsed Doppler with two dimensional echocardiographic imaging are highly accurate in identifying the lesions present. Quantification of the severity of stenotic lesions requires calculation of the pressure gradient across the valve and estimation of valve area; quantification of volume flow rate is frequently helpful. The pressure gradient is calculated from high velocity data acquired in the stenotic valve orifice by using the Bernoulli equation. Volume flow rate through the valve can be estimated by using Doppler velocity data and two-dimensional echocardiographic imaging data acquired at sites upstream from the stenotic valve. The continuity equation allows calculation of valve area that is based on this noninvasive stroke volume and pressure gradient data. This review characterizes flow patterns present near stenotic valves, discusses the equations required to quantify aortic and pulmonic stenosis, and then describes the clinical approach to the noninvasive quantification of both stenotic lesions. PMID- 1884485 TI - Quantification of valvular regurgitation by Doppler echocardiography. AB - One of the widest uses of color Doppler echocardiography is for the quantification of valvular regurgitation. In this article we review the physics and instrumentation factors related to the most commonly applied method, that of planimetering areas of regurgitant jet spray within the receiving chamber, and relate features such as instrument gain, pulse repetition frequency, and important physical parameters such as receiving chamber compliance and driving pressure to the application of this method for precordial as well as transesophageal echocardiography. New approaches to the quantification of valvular insufficiency, such as measurement of the momentum of the jet and study of the acceleration flow in the proximal flow convergence region within the chamber of origin of an insufficiency jet and proximal to the orifice, are described and preliminary results given for a new method of quantification of volume flow across regurgitant orifices. PMID- 1884486 TI - Role of echocardiography in the diagnosis and evaluation of severity of mitral and tricuspid stenosis. AB - The presence, severity, and hemodynamic consequences of mitral and tricuspid stenosis can be determined by echocardiographic techniques. In mitral stenosis two-dimensional echocardiographic imaging allows definition of leaflet anatomy and dynamics, subvalvular disease, ventricular function, and involvement of other valves. Spectral and color Doppler echocardiographic techniques permit accurate measurement of transvalvular gradient, determination of functional orifice area, evaluation of associated valvular regurgitation, and assessment of pulmonary artery pressures. These approaches are of recognized clinical value, and they provide additional diagnostic information that is unavailable from clinical assessment alone in a significant number of patients. Compared with available invasive diagnostic standards of reference, echocardiographic data have been found to be comparable in accuracy. In tricuspid stenosis echocardiographic imaging and Doppler techniques provide an assessment of valve morphology and function that should be similarly useful in clinical management decisions, although rigorous comparative studies have not been performed. Currently, carefully done echocardiographic studies are a definitive means of establishing the presence and significance of mitral stenosis and tricuspid stenosis, thereby obviating the need for invasive evaluation in many patients, reducing risk, and potentially decreasing the cost of diagnostic assessment. PMID- 1884487 TI - Evaluation of valvular heart disease with cine gradient echo magnetic resonance imaging. AB - Electrocardiographic referenced repetitive gradient echo magnetic resonance imaging (cine GRE) has been used to detect and quantify valvular regurgitation. Regurgitation is recognized as a signal void in the high intensity blood pool on these images. Mitral regurgitation causes a signal void in the left atrium in systole, and aortic regurgitation produces one in the left ventricle in diastole. The specificity, sensitivity, and diagnostic accuracy of cine GRE for the detection of mitral and aortic regurgitation was greater than 0.93, 0.89, and 0.92, respectively. The severity of regurgitation has been quantified as the difference in the stroke volume between the two ventricles by measuring the volume of the blood pool, as shown in the stack of magnetic resonance tomograms. Severity has also been assessed by measuring the volume of the signal void. Finally, measurements of the volume of aortic regurgitation have recently been achieved by using velocity-encoded cine GRE. This technique provides a direct measurement of retrograde flow in the aorta during diastole. New cine GRE imaging techniques provide a noninvasive means for quantification of valvular as well as ventricular function. PMID- 1884488 TI - Radionuclide angiographic evaluation of left ventricular diastolic function. AB - Left ventricular diastolic function is altered in the majority of patients with cardiac diseases, especially those characterized by myocardial ischemia or hypertrophy. In many circumstances, such abnormalities related to impaired relaxation or reduced distensibility may precede evidence of left ventricular systolic dysfunction. Radionuclide angiography may be adapted to study the rapid filling phase of diastole, the duration of the isovolumic relaxation phase, the relative contributions of rapid filling and atrial systole to left ventricular stroke volume, and the relation between regional nonuniformity of left ventricular function and global filling properties. Technical aspects of data acquisition that must be considered for such studies include the effects of cardiac cycle length fluctuations, temporal resolution, temporal smoothing, and normalization parameters. As noninvasive radionuclide methods (and any other analyses using purely noninvasive techniques) do not permit assessment of the left atrial-left ventricular pressure gradient or the simultaneous evaluation of changes in left ventricular pressure and volume during relaxation and filling, complete clinical interpretation of "abnormal" left ventricular filling indexes, or changes in these indexes after interventions, is not possible. Despite the inherent limitations of noninvasive assessment of left ventricular diastolic function, radionuclide evaluation of left ventricular filling may provide clinically useful insights, especially in patients with congestive heart failure symptoms and normal left ventricular systolic function. PMID- 1884489 TI - Nuclear magnetic resonance imaging for assessment and follow-up of patients with valve disease. AB - Nuclear magnetic resonance (NMR) imaging now offers a powerful means of assessing a variety of clinically important parameters in patients with valvular heart disease. NMR approaches will probably be most useful in patients with chronic valvular regurgitation, in which there continues to be uncertainty regarding the optimum timing for surgical intervention. In these patients it is possible to simultaneously assess both the valvular regurgitation and the resulting changes in myocardial structure and function. In patients with aortic stenosis, NMR can be applied to the assessment of left ventricular mass, both before and after valvuloplasty or valve replacement. In mitral stenosis, NMR may be applied to the assessment of right ventricular volumes and function. NMR may be used for the detection of prosthetic valve regurgitation when Doppler studies are equivocal. Finally, NMR imaging may be applied in patients with congenital or aortic root disease to evaluate valvular function in addition to diagnostic assessment of such patients. The future development of isotropic three-dimensional acquisition approaches, ultrafast imaging strategies, automated surface detection techniques, and more rapid function and flow analysis could considerably enhance the use of the current NMR approaches. The application of spectroscopic techniques could provide a means of monitoring myocardial metabolic abnormalities in ventricles exposed to chronic overload. Meanwhile, in patients with valvular regurgitation and stenosis, it would seem timely to initiate long-term serial NMR studies to further define natural history and the effects of various medical regimens and to ultimately help determine optimum medical and interventional regimens. PMID- 1884490 TI - Clinical cardiac positron emission tomography: state of the art. AB - Cardiac positron emission tomography (PET) has evolved rapidly from a relatively esoteric research tool into clinical applications providing unique, quantitative information on myocardial perfusion, metabolism, and cell membrane function and having a potentially significant impact on cardiovascular medicine. Although there are many different positron radionuclides for imaging diverse myocardial behavior, three radionuclides have reached accepted clinical utility. Cardiac PET using nitrogen-13-ammonia, rubidium-82, and fluoro-18-deoxyglucose has proved accurate and definitive in multiple university and private-practice sites for diagnosing and assessing severity and location of coronary artery disease in symptomatic or asymptomatic patients, for identifying injured but viable myocardium potentially salvageable by revascularization, and for ruling out clinically significant coronary artery stenosis with a high specificity in patients who might otherwise undergo coronary arteriography to document the absence of significant disease. PMID- 1884491 TI - Echocardiographic assessment of prosthetic valves. PMID- 1884492 TI - The role of echocardiography/Doppler in catheter balloon treatment of adults with aortic and mitral stenosis. AB - Doppler and two-dimensional echocardiography (2DE) have played a major role in the evaluation of patients undergoing catheter balloon treatment of aortic and mitral stenosis. Doppler/2DE has made possible an understanding of the mechanism of increase in valve area. Before the procedure, Doppler/2DE provides a reasonable estimate of the severity of the valvular stenosis and associated cardiac abnormalities. The evaluation of mitral valve morphology by 2DE before catheter balloon treatment has shown that patients with excellent leaflet motion and minimal increase in valve thickness have the greatest increase in mitral valve area. During the procedure, Doppler/2DE can aid in the transseptal puncture, in positioning the balloons across the stenotic orifice, and in the immediate assessment of changes in valve function and complications. The estimate of the aortic and mitral valve gradients and areas by Doppler/2DE before catheter balloon treatment shows a reasonable correlation with hemodynamic measurements. Immediately after the procedure, the Doppler/2DE estimates of aortic valve gradient and area show a fair correlation with data from cardiac catheterization, provided care is taken to avoid technical problems. Doppler/2DE assessment of mitral valve area immediately after catheter balloon commissurotomy (CBC) shows a poor correlation with catheterization data, which has been attributed to rapid changes in left atrial compliance and gradient. However, the correlation of Doppler estimates of mitral valve area with catheterization data improves at 3 months after CBC. Serial evaluations of patients after aortic or mitral catheter balloon dilatation should permit detection of restenosis and valve regurgitation and assessment of ventricular function and may provide valuable insights into the mechanisms of restenosis and changing clinical status. PMID- 1884493 TI - The use of color flow mapping for intraoperative assessment of valve repair. AB - Repair procedures that preserve a patient's native valve are associated with a lower perioperative and late mortality, a lower incidence of thromboembolic events, and better preservation of left ventricular function than prosthetic replacement. Traditionally employed procedures for intraoperative assessment of the adequacy of repair, such as fluid injection into the arrested ventricle for assessment of valve leakage, measurement of atrial pressure and height of V waves, and palpation of the atria for the presence of systolic thrills, have not proved to be reliable approaches in the intraoperative evaluation of mitral and tricuspid regurgitation and in the assessment of the adequacy of repair procedures. Intraoperative color Doppler, using either the epicardial or the transesophageal approach, offers rapid and accurate information about the presence and severity of mitral regurgitation at the time of surgery. This technique provides instantaneous evaluation of the adequacy of mitral and tricuspid valvuloplasty and appears capable of predicting postoperative outcome. Intraoperative color Doppler is useful for evaluation of the adequacy of repair before chest closure and may thus help to avoid the need for reoperation. This approach may ultimately allow valve repair procedures to be performed in greater numbers of patients with better control over outcome and with lower reoperation rates. PMID- 1884494 TI - Valvular heart disease: management and intervention. Clinical overview and discussion. AB - The diagnosis and estimation of severity of valvular disease can usually be made by a well done history and physical examination. We now have a wealth of noninvasive techniques capable of imaging the heart and the great vessels. With Doppler echocardiography and magnetic resonance imaging we are beginning to develop methods that can measure pressures and flow. All of these advances have duplicated to a large extent the information obtainable in the past only from cardiac catheterization and angiography. In some instances, in aortic and mitral stenosis, for example, echo-Doppler evaluation is so good that catheterization is rendered unnecessary. The decision to send patients to surgery without catheterization is especially secure when the valvular obstruction is very severe. When the gradient is only moderately increased, then estimation of severity depends on flow, and in many cases these patients are sent to catheterization before surgery is recommended. With regurgitant lesions there is less confidence with noninvasive techniques that the severity is always correctly estimated, and therefore catheterization and angiography are more often necessary before sending the patient to surgery. At the present time cardiac catheterization and angiography are required 1) whenever there is an inconsistency between the clinical picture and noninvasive information, for example, the symptomatic patient with aortic stenosis who has mild-to-moderate aortic stenosis by echo-Doppler techniques, and 2) whenever additional information not obtainable by noninvasive techniques is necessary, for example, the need to know the status of the coronary arterial circulation. Noninvasive techniques have not in any way replaced a good history and physical examination.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1884495 TI - Metabolic imaging of patients with cardiomyopathy. AB - The cardiomyopathies comprise a diverse group of illnesses that can be characterized functionally by several techniques. However, the delineation of derangements of regional perfusion and metabolism have been accomplished only relatively recently with positron emission tomography (PET). Regional myocardial accumulation and clearance of 11C-palmitate, the primary myocardial substrate under most conditions, demonstrate marked spatial heterogeneity when studied under fasting conditions or with glucose loading. PET with 11C-palmitate permits the noninvasive differentiation of patients with nonischemic from ischemic dilated cardiomyopathy, since patients with ischemic cardiomyopathy demonstrate large zones of intensely depressed accumulation of 11C-palmitate, probably reflecting prior infarction. Patients with hypertrophic cardiomyopathy and Duchenne's muscular dystrophy demonstrate relatively unique patterns of myocardial abnormalities of perfusion and metabolism. The availability of new tracers and techniques for the evaluation of myocardial metabolism (11C-acetate), perfusion (H2(15)O), and autonomic tone (11-C-hydroxyephedrine) should facilitate further understanding of the pathogenesis of the cardiomyopathies. PMID- 1884496 TI - Antimyosin imaging in cardiac transplant rejection. AB - Fab fragments of antibodies specific for cardiac myosin have been labeled with indium-111 and injected intravenously into animals and into patients with heart transplants. The antibodies, developed by Khaw, Haber, and co-workers, localize in cardiac myocytes that have been damaged irreversibly by ischemia, myocarditis, or the rejection process. After clearance of the labeled antibody from the cardiac blood pool, planar imaging or single photon emission computed tomography is performed. Scintigrams reveal the uptake of the labeled antimyosin in areas of myocardium undergoing transplant rejection. In animal studies, the degree of antimyosin uptake appears to correlate significantly with the degree of rejection assessed at necropsy. In patients, the correlation between scans and pathologic findings from endomyocardial biopsy is not as good, possibly because of sampling error in the endomyocardial biopsy technique. The scan results at 1 year correlate with either late complications (positive) or benign course (negative). Current limitations of the method include slow blood clearance, long half-life of indium-111, and hepatic uptake. Overcoming these limitations represents a direction for current research. It is possible that from these efforts a noninvasive approach to the diagnosis and evaluation of cardiac transplantation may evolve that will decrease the number of endomyocardial biopsies required to evaluate rejection. This would be particularly useful in infants and children. PMID- 1884497 TI - Two-dimensional echocardiographic determination of left ventricular volume, systolic function, and mass. Summary and discussion of the 1989 recommendations of the American Society of Echocardiography. AB - The quantitation of two-dimensional echocardiographic images has been frustrated by the lack of concrete recommendations. The recent statement by the American Society of Echocardiography has rectified that deficiency. This discussion reviews the recommendations of the Society, focusing on the general and technical considerations for quantitation, computational equipment, cavity volume measurements, and the quantitation of left ventricular mass. The author's recent experience with directing a quantitative laboratory is discussed. In particular, the advantage of on-line bedside quantitation and mass storage of images and measured parameters is presented. An example of a digitized study is given along with measuring methodology. PMID- 1884498 TI - Doppler echocardiographic evaluation of diastolic dysfunction. AB - Recently, considerable effort has been directed toward the application of Doppler methods for detecting diastolic dysfunction. Recordings of transmitral filling velocity as obtained from pulsed-wave Doppler have been extensively investigated as a noninvasive method for determining left ventricular diastolic filling properties. Although Doppler parameters appear to reflect volumetric transmitral flow, close correlations with invasive descriptors of diastolic performance have not been found. Furthermore, Doppler transmitral velocities are sensitive to changes in ventricular preload, afterload, and heart rate. However, at least two distinct Doppler spectral patterns have been identified that are associated with impaired ventricular relaxation and restrictive physiology. Thus, Doppler recordings have proven to be of value in identifying the presence and type of diastolic dysfunction, and in the future they may be helpful in following the response to therapeutic interventions. The purpose of this paper is to review the available information relating Doppler transmitral recordings with catheterization and clinical descriptors of diastolic function. Additionally, the aim is to provide an understanding of the value and limitations of these noninvasive measurements in identifying and treating patients with diastolic abnormalities. PMID- 1884499 TI - Radionuclide angiography in the management of asymptomatic aortic regurgitation. AB - Left ventricular systolic function is an important determinant of long-term prognosis in patients with chronic aortic regurgitation. In patients undergoing aortic valve replacement, those with preoperative left ventricular dysfunction have a greater risk of postoperative congestive heart failure and death than do those in whom preoperative left ventricular systolic function is normal. However, patients with preoperative left ventricular dysfunction are not a homogeneous group but may be further stratified according to risk on the basis of the severity of symptoms, exercise intolerance, and temporal duration of left ventricular dysfunction. Therefore, asymptomatic patients with reproducible and definite evidence of impaired left ventricular function should undergo operation without waiting for the development of symptoms or more severe left ventricular dysfunction. In addition, among asymptomatic patients with normal systolic function, indexes of left ventricular function are also helpful, especially when measured serially, in predicting the development of symptoms and the need for valve replacement surgery over the course of the next 5 to 10 years. Noninvasive imaging techniques should play a major role in this evaluation, and radionuclide angiography is ideally suited for the quantitative evaluation of systolic function in the volume-overloaded left ventricle. Although the prognostic value of left ventricular ejection fraction at rest is well established, ejection fraction during exercise has little value once age and left ventricular function at rest are accounted for and is of minor importance in formulating patient management decisions. PMID- 1884500 TI - Echocardiography and Doppler ultrasound in the evaluation of pericardial disease. AB - Echocardiography and Doppler ultrasound are useful in evaluating a variety of pathological conditions affecting the pericardium. Cardiac tamponade results in right atrial collapse and right ventricular diastolic collapse detectable by echocardiography. These echocardiographic signs have a high degree of sensitivity and specificity. False-negative echocardiographic studies may be seen in patients with pulmonary hypertension, and false-positive studies for cardiac tamponade may occur in severe hypovolemia. Although cardiac tamponade is usually caused by pericardial effusion, less commonly intrapericardial clot may result in hemodynamic compromise. Pericardial clot may be echogenic, and hence the diagnosis potentially can be missed. If the intrapericardial clot is localized, the classic echocardiographic signs of pericardial effusion may be absent, and a localized mass may be seen on the echocardiogram. Increased respiratory variation in transvalvular blood flow velocities detectable by Doppler ultrasound is found in cardiac tamponade. Doppler ultrasound studies may be particularly useful in those patients in whom the characteristic echocardiographic abnormalities are absent. Both M-mode and two-dimensional echocardiography may be useful in diagnosing pericardial thickening. Constrictive pericarditis results in a variety of echocardiographic abnormalities including pericardial thickening; biatrial enlargement with good left ventricular function; a diastolic septal bounce; and a dilated inferior vena cava without significant respiratory variation. Doppler echocardiographic abnormalities are commonly found in constrictive pericarditis. Echocardiography is also useful as a guide to performing pericardiocentesis and in the detection of pericardial adhesions and pericardial metastases. PMID- 1884501 TI - Magnetic resonance imaging of great vessel, myocardial, and pericardial disease. AB - The outstanding ability of magnetic resonance imaging to provide anatomic information over a large field of view in any plane in patients of all sizes and body habitus has made it the current modality of choice for evaluating the thoracic aorta and for differentiating constrictive pericarditis from restrictive cardiomyopathy. The lack of radiation exposure makes it particularly advantageous for patients requiring serial studies. It serves as an important clinical adjunct to ultrasound in evaluating diseases of the abdominal aorta, other great vessels, the myocardium, and the pericardium. Myocardial function, thickness, and mass can be assessed without geometric assumptions. Myocardial tagging offers a unique way to study cardiac biomechanics. The combination of anatomic and quantitative functional information becoming available in clinically reasonable acquisition times makes magnetic resonance imaging an increasingly attractive noninvasive tool. The contribution of tissue characterization has been disappointing, but may improve with utilization of contrast agents; that of in vivo spectroscopy remains investigational. PMID- 1884502 TI - Echocardiographic assessment of atherosclerotic coronary lesions. AB - Echocardiographic techniques to visualize normal and atherosclerotic coronary arteries include transthoracic, transesophageal, epicardial (intraoperative), and intravascular approaches. All are capable of visualizing portions of the coronary arteries, especially proximal, and demonstrating atherosclerotic lesions. However, none of these methods are able, at present, to completely examine the coronary tree, and therefore none are ready to be used as a standard clinical technique for the diagnosis and management of coronary artery disease. Technological advances will enhance the future clinical value and applicability of these techniques. PMID- 1884503 TI - Stress echocardiography for detection of coronary artery disease. AB - Stress echocardiography is a relatively new technique that combines cardiovascular stress with echocardiographic imaging for the diagnosis of coronary artery disease. It is based on the hypothesis that stress-induced ischemia will result in regional wall motion abnormalities that can be detected by two-dimensional echocardiography or abnormalities of global function that can be detected with Doppler ultrasound. Its accuracy for detecting coronary artery disease is high enough to allow for clinical use. In such a role it has added value to the analysis of the routine electrocardiogram and symptoms during exercise. In the patient unable to exercise, pharmacological stress with the use of dobutamine or dipyridamole are realistic alternatives. In addition to the diagnosis of coronary disease, stress echocardiography can be used to demonstrate recovery of function after interventions and to assess prognosis after myocardial infarction. PMID- 1884504 TI - Overview: diagnosis of ischemic heart disease by noninvasive techniques. AB - Noninvasive tests have greatly improved in their ability to diagnose coronary artery disease. In addition, new testing modalities have been added to our armamentarium. However, no test is clearly superior to all others in every clinical circumstance. Moreover, none have been shown to provide sensitivities and specificities consistently above 90%. Therefore, their use for diagnostic purposes in populations with a lower prevalence of disease is only of moderate value. Conversely, for the assessment of the functional significance of coronary artery disease or prognosis in patients with ischemic heart disease, the addition of noninvasive imaging modalities to exercise testing is of high value. PMID- 1884505 TI - Exercise radionuclide angiocardiography predicts cardiac death in patients with coronary artery disease. AB - The purpose of this investigation was to document the relative importance of three clinical and three radionuclide variables for prediction of cardiac death in a consecutive group of patients evaluated for coronary artery disease. During a 6 1/2-year period, beginning in January 1978, 2,042 consecutive patients underwent radionuclide angiocardiography, with a clinical diagnosis of coronary artery disease, at Duke University Medical Center. A subgroup of 318 patients who underwent surgical myocardial revascularization near the time of initial study were excluded from later analysis. Clinical follow-up information was complete in a group of 1,663 patients who did not undergo interventional therapy. The 141 cardiac deaths in these 1,663 patients were the study end point. Cox proportional hazards models analyzed the prognostic information contained in three clinical variables (pain type, age, and sex) and three radionuclide angiocardiogram variables (exercise ejection fraction, resting end-diastolic volume, and change in heart rate with exercise). One-variable models confirmed the prognostic importance of each of these six variables. A multivariable model in which all six variables were used showed clinical variables to contain only 5% and the radionuclide variables 95% of the prognostic information. The exercise ejection fraction was the single most important variable, which alone contained 85% of the total information in the model. Curves relating probability of no cardiac death to the exercise ejection fraction identified a value of 0.50 as an inflection point. Patients with exercise ejection fractions below 0.50 demonstrate a probability of cardiac death that increases as the ejection fraction decreases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1884506 TI - Myocardial perfusion imaging with thallium-201 to evaluate patients before and after percutaneous transluminal coronary angioplasty. AB - Thallium-201 imaging may be used to help determine the distribution and amount of myocardium in jeopardy and the success of revascularization after percutaneous transluminal coronary angioplasty. Single photon emission computed tomography is particularly advantageous because of its ability to differentiate vascular territories and thus evaluate patients with multivessel disease. Myocardial infarction resulting from complications such as distal embolization and side branch occlusion can be detected. Thallium-201 imaging early after angioplasty may show abnormal results caused by transiently insufficient coronary flow reserve. However, studies performed 6 weeks or more after angioplasty accurately detect early restenosis and may identify those individuals likely to become symptomatic and eventually develop restenosis in the future. PMID- 1884507 TI - Use of echocardiography for patient management in chronic ischemic heart disease. AB - Myocardial ischemia causes regional myocardial contractile and relaxation abnormalities. The extent of ischemia is determined by the distribution and severity of coronary artery stenoses. In coronary heart disease, two powerful predictors of prognosis are the coronary anatomy and ventricular function. Management in coronary heart disease is directed by accurate diagnosis and individualized objectives. Echocardiography at rest and exercise, combined with Doppler and color flow imaging, are properly applied to the differential diagnosis of common clinical syndromes in ischemic heart disease, the identification of the proximal coronary arteries, and the effects of ischemia and prior infarction. Subsequent use of coronary arteriography partially depends on the philosophy regarding the applicability of coronary surgery or angioplasty in an individual patient. Prediction of multivessel, left main, or proximal left anterior descending coronary artery disease by extensive wall motion abnormalities or an abnormal left ventricular ejection fraction may direct the clinician to coronary arteriography to select among coronary surgery, angioplasty, or medical management. PMID- 1884508 TI - Computed tomography for patient management in coronary artery disease. AB - Computed tomography (CT) represents the optimum theoretical approach to x-ray imaging. This conclusion results from an awareness of CT's capacity to solve the fundamental limitation of all forms of x-ray imaging--the superimposition of anatomic structures. Because CT is potentially a fully three-dimensional method, this problem is addressed in a manner not subject to the risks, complications, and technical limitations of selective angiography, subtraction angiography, tomography, and other techniques. Ultrafast CT provides a broad spectrum of useful quantitative cardiac data during one minimally invasive procedure. Therefore, the optimism for cine CT imaging of the heart is well founded. Apart from the demonstration of anatomic structures in any reconstructed plane and in movie format, without the need for any form of electrocardiographic gating, this new generation of millisecond CT scanners offers a unique potential for measuring myocardial mechanics and perfusion. Myocardial integrity can be evaluated by measuring myocardial wall thickening, which is a sensitive indicator of blood flow. It can also be assessed by time-density changes derived from analyzing the passage of contrast medium through thin slices of myocardium. Feasibility studies have demonstrated that this should be possible in the clinical setting by use of fast CT scanning. The radiation exposure to the patient with cine CT is low and comparable to, or less than, that of conventional CT and 10-15% of that received during angiocardiography; therefore, it is not a practical limitation. Further clinical and research studies are needed to determine the future role of this exciting new modality in the diagnosis and management of patients with heart disease. PMID- 1884509 TI - Clinical overview of management of chronic ischemic heart disease. AB - The outcome of patients with chronic coronary artery disease is dependent on many factors; the most important ones include the severity and extent of coronary artery disease, state of left ventricular function at rest, extent and severity of myocardial ischemia, and the total amount of left ventricular myocardium that is at risk. To use noninvasive tests optimally, the clinician first must define the information needed. The sensitivity, specificity, and predictive accuracy of the test(s) in providing the necessary information, the additive value of the result of a test to the information already available, and the best combination of tests in providing the desired information help determine the choice of various noninvasive tests in a particular clinical circumstance. PMID- 1884510 TI - Value of regional wall motion abnormality in the emergency room diagnosis of acute myocardial infarction. A prospective study using two-dimensional echocardiography. AB - Because regional wall motion abnormality (RWMA) is usually noted during ischemia, we hypothesized that the presence of this finding with two-dimensional echocardiography would be superior to conventional methods of diagnosing acute myocardial infarction (AMI) in the emergency room. We also hypothesized that because the absence of RWMA would probably not be associated with AMI, the use of two-dimensional echocardiography would significantly limit unnecessary hospital admissions. To test these hypotheses, we undertook a prospective study that used two-dimensional echocardiography in 180 patients presenting to the emergency room with symptoms suggestive of AMI. The emergency room physicians were not informed of the two-dimensional echocardiography findings, and their decision to admit or not admit to the hospital was based on conventional clinical and electrocardiographic criteria. Forty patients were not admitted to the hospital and 140 were admitted. Of the 30 patients with enzyme-confirmed AMI, nine had typical ST elevation on the ECG that was consistent with acute injury, three had normal ECGs, and eight had ECGs in the presence of which AMI could not have been diagnosed (left bundle branch block, paced rhythm, or repolarization changes); the rest had nonspecific ECG findings. Of the 29 AMI patients with technically adequate two-dimensional echocardiography studies, two did not demonstrate RWMA and 27 had RWMA, compared with nine with diagnostic ECG changes (p less than 0.001). Of the 13 patients with in-hospital complications only four had an initial ECG showing ST elevation, and all 13 had RWMA (p less than 0.001).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1884511 TI - Rest and exercise radionuclide angiography for diagnosis in chronic ischemic heart disease. AB - Rest and exercise radionuclide angiography is frequently employed for the diagnosis of chest pain syndromes. Its value and limitations in this regard have been well studied, but proper utilization of the technique requires an understanding of five critical concepts: 1) Radionuclide angiography is superior to treadmill exercise testing and probably equivalent to thallium scintigraphy, although the published series did not use current methods. 2) The true specificity of radionuclide angiography is about 80%, intermediate between the early optimistic estimates and the later pessimistic ones. 3) The peak exercise ejection fraction is the preferred test parameter for diagnosis, although exercise hemodynamics, symptoms, and electrocardiographic changes should also be considered. 4) Although radionuclide angiography is clearly helpful for noninvasive diagnosis, significant numbers of patients will continue to fall in an uncertain category. 5) The proper application of the technique requires recognition of its limitations and careful attention to technical details. When properly applied, this modality can make an important contribution to clinical decision making. PMID- 1884512 TI - Long-term follow-up in females with Ullrich-Turner syndrome. AB - In accordance with Nielsen & Stradiot's protocol (1987), we report on the long term follow-up in 50 adult females with Ullrich-Turner syndrome. Attention is drawn mainly to social problems. PMID- 1884513 TI - The inheritance of conotruncal malformations: a review and report of two siblings with tetralogy of Fallot with pulmonary atresia. AB - Congenital heart defects (CHD) are a group of structural abnormalities that in humans have a combined incidence of approximately 1%. It is estimated that 4-5% of CHD are associated with chromosome abnormalities, 1-2% are associated with single gene syndromes, 1-2% are due to known teratogens, with the rest presumably determined multifactorially. We report on a brother and sister with tetralogy of Fallot with pulmonary atresia, and review the inheritance of familial conotruncal anomalies. We feel the small number of family clusters and the rare instances of consanguinity in non-syndromal conotruncal defects are consistent with multifactorial determination. While it is prudent in counseling families with 2 or more individuals with conotruncal CHD to raise the possibility of single gene inheritance, we believe that current empiric recurrence risk estimates most accurately reflect their risks. PMID- 1884514 TI - Identification of the 664 proline to leucine mutation in the low density lipoprotein receptor in four unrelated patients with familial hypercholesterolaemia in the UK. AB - Mutations in the gene for the low density lipoprotein (LDL) receptor cause Familial Hypercholesterolaemia (FH). One such mutation, a cytosine to thymine change in the codon for amino acid 664, causes proline (CCG) to be replaced by leucine (CTG) at this position, and creates a Pst I site in exon 14 of the gene. This mutation, previously identified in an FH homozygote of Asian Indian origin, results in a receptor with a reduced binding affinity for LDL and in delayed processing of the precursor form of the protein in cultured cells. A total of 224 unrelated heterozygous and 4 homozygous FH patients from London was screened for this mutation using direct amplification of genomic DNA by the polymerase chain reaction (PCR) and restriction digestion of the PCR product. Four patients were identified who were heterozgous for this mutation and the C to T base change was confirmed by sequencing. Affected relatives of these patients were also found to have the mutation. The effect of the mutation on LDL-receptor function in lymphoblastoid cell lines obtained from two of these patients was similar to that observed in heterozygous relatives of the original proband (MM). Eight polymorphisms of the LDL receptor gene were used to determine the haplotype of the defective allele carried by the patients and the individual (MM) in whom the mutation was first discovered. Two different haplotypes were found, suggesting that the mutation, which occurs at a CpG 'hotspot', has arisen independently at least twice. The presence of the same single base change in the LDL-receptor gene in several unrelated patients has not previously been reported in a population which is not geographically or culturally isolated. PMID- 1884515 TI - Germinal mosaicism in Crouzon syndrome. A family with three affected siblings of normal parents. AB - Germinal mosaicism is reported in three siblings with Crouzon syndrome born to normal, unrelated parents. Other probable explanations for the features in this family are discussed. PMID- 1884516 TI - Clinical investigation of females with the Martin-Bell syndrome and risk assessment for carrier status. AB - Anthropometric measurements were made on a series of females heterozygous for the fragile-X syndrome. It was found that there were no simple series of discriminating features separating those of normal IQ from the mentally handicapped, but rather that the carriers studied represented a wide spectrum of phenotype. When measurements performed on 15 FRAXA negative, obligate carriers of normal IQ were considered separately, it was found that there were certain common phenotypic features allowing risk figures to be amended for those females at 50% risk of being a carrier but who are also FRAXA negative. PMID- 1884517 TI - A simplified protocol for fluorescence in situ hybridization with repetitive DNA probes and its use in clinical cytogenetics. AB - A method for chromosome-specific staining and its use in clinical cytogenetics is described. This fluorescence in situ hybridization protocol for repetitive DNA probes results in yellow-green fluorescent signals on orange-red stained chromosomes. Special characteristics are its simplicity, the use of digoxigenin 11-dUTP for labeling, and the combination of high stringency criteria for hybridization and low stringency for washing. The method is particularly advantageous in cases with structurally abnormal extra chromosomes (ESACs), marker chromosomes of gonosomal origin, and chromosomal mosaicism. It may also facilitate the screening of cases for fragile X. The chromosome-specific staining can be done within 1 working-day. PMID- 1884518 TI - A balanced complex chromosomal rearrangement (BCCR) with phenotypic effect. AB - The authors report on a case of balanced complex chromosomal rearrangement (BCCR) with phenotypic effect, describe the dysmorphisms and malformations observed, and discuss the various pathogenetic mechanisms. On the basis of these considerations, they underline the need for careful reporting of examined cases, distinguishing the characteristic signs from dysmorphisms that are described in several other chromosomal aberrations as well. Finally, they stress the importance of a more precise description of BCCRs for the purpose, among others, of a correct formulation of reproductive risk. PMID- 1884519 TI - An apparently new mental retardation syndrome in three elderly sisters. AB - Three elderly sisters with profound mental retardation in association with the clinical features of microcephaly, short stature, brachydactyly type D, flattened occiput, down-slanting palpebral fissures, low-set large ears, broad prominent nose and kyphoscoliosis have been investigated. Each was more than 60 years of age and their clinical features were strikingly similar. The disorder has several manifestations in common with Rubenstein-Taybi syndrome and appears to be inherited as an autosomal recessive in this family. PMID- 1884520 TI - Robertsonian translocation and an extra microchromosome: independent origin identified by in situ hybridisation. PMID- 1884521 TI - Nursing education as social reform. PMID- 1884522 TI - Socializing nursing students to NSNA membership. PMID- 1884523 TI - Abstracts. Annual meeting, Canadian Society for Clinical Investigation, The Royal College of Physicians and Surgeons of Canada, and participating societies. Quebec, September 19-23, 1991. PMID- 1884525 TI - Peripheral and central nervous system involvement in essential mixed cryoglobulinemia: a case report. AB - We describe a man with essential mixed cryoglobulinemia who developed peripheral neuropathy and multiinfarctual encephalopathy. Vasculitis was observed in the vasa nervorum and in the small vessels of the brain. The possible pathogenetic role of the cryoglobulins in the nervous system lesions is discussed. PMID- 1884524 TI - Muscle biopsy in Alzheimer's disease: morphological and biochemical findings. AB - Recent evidences of a predisposing genetic factor associated with Alzheimer's disease (DAT) suggests that important alterations may be expressed in tissues other than the brain. We present morphological and biochemical studies on muscle obtained from ten patients with Alzheimer's disease and coeval controls. Muscle biopsy examination showed an increased subsarcolemmal mitochondrial oxidative activity in three patients. The biochemical studies showed an increased oxidative enzyme activity only in the DAT group. The CoQ10 level, studied so far in three DAT patients, was greatly reduced (approximately 50%) compared with controls. Possible new peripheral markers in Alzheimer's disease will be discussed. PMID- 1884527 TI - 23rd Danube Symposium, an Erwin-Riesch Symposium for Neurological Sciences. Berlin, October 11-13, 1990. PMID- 1884526 TI - The anatomy of aneurysm-bearing circles of Willis. AB - The circle of Willis is known to exhibit considerable anatomical variability. The incidence of variations of the circle is said to be greater when an aneurysm is present, particularly one of the anterior communicating artery. In this study 40 circles of Willis bearing 51 saccular aneurysms were dissected and examined macroscopically. Forty circles from patients with other neurological diseases served as controls. Ninety-seven per cent of circles bearing aneurysms showed variations from a hypothetical "normal" structure, as did 85% of controls. The aneurysm group as a whole, and circles bearing anterior communicating aneurysms, showed a higher incidence of anterior cerebral artery asymmetry than controls (p less than 0.001), as did the latter when compared with circles bearing aneurysms at other sites (p less than 0.01), but there were no other significant differences. PMID- 1884528 TI - IIB osteosarcoma. Current management and survival statistics in the USSR. AB - Three hundred and ninety-three patients with IIB osteosarcoma were treated at the author's institution between 1955 and 1986. In the first stage of the study, 88 patients were treated with surgery only. The five-year disease-free survival rate was 7%. In the second stage of the study, the efficacy of preventive chemotherapy after radical surgery was studied in 55 patients. The five-year disease-free survival rate was 34.4%. In the third stage of the study, the efficacy of combination therapy consisting of preoperative treatment, limb-saving surgery, and preventive chemotherapy was studied in 66 patients. The five-year disease free survival rate was 35.5%. The authors examined results in 21 patients with Grade IV responses to evaluate the relationship between prognosis and morphogenic changes after preoperative radiotherapy and chemotherapy. The five-year disease free survival rate was 57.9%. In the fourth stage of the study (conducted in 1986), two regimens of preoperative chemotherapy were initiated. The first regimen consists of intraarterial platinum infusions to patients with lower extremity bone damage. The second regimen consists of high-dose methotrexate infusions. The preliminary conclusion is that primary tumor damage is significantly more marked after intraarterial cisplatin infusion. PMID- 1884530 TI - Survival and management considerations in postirradiation osteosarcoma and Paget's osteosarcoma. AB - Postirradiation and Paget's osteosarcomas are high-grade malignancies. The five year survival was only 10% in recent experience at the author's institution. Progressive pain is an important clinical feature in both conditions. Careful roentgenographic studies demonstrate cortical destruction and a soft-tissue mass in virtually all patients. Metastasis was present in 25% of both groups of patients at presentation. In contrast to previous series, more than 80% of the patients with postirradiation osteosarcoma had had irradiation for malignant entities and more than 70% had been treated with modern radiotherapy regimens (cobalt-60 or linear accelerator). Twice as many patients with postirradiation osteosarcoma were evaluated and treated in the 1980s than in the previous decade. The initial indication for irradiation often was carcinoma of the breast, uterus, or cervix, or lymphoma. Two-thirds of the patients had progressive disease that was not controllable within six months after diagnosis. Early detection may be the only effective means of improving survival with postirradiation or Paget's osteosarcoma. These patients require lifelong follow-up evaluations. PMID- 1884529 TI - IIB osteosarcoma. Current management, local control, and survival statistics--the Australian experience. AB - Current management of osteosarcoma at the authors' institution involves intraarterial induction chemotherapy using intermittent cycles of cisplatin and doxorubicin (Adriamycin), surgical resection with limb-sparing wherever possible, and adjuvant systemic chemotherapy (high-dose methotrexate with retrieval and doxorubicin). Twenty cases treated in this way between May 1983 and May 1989 are reviewed. There were 18 Stage IIB osteosarcomas and two Stage IIB malignant fibrous histiocytomas. Chemotherapeutic effect was evaluated in the resected tumors. There was little correlation between the clinical response to the induction chemotherapy and cell necrosis present in the resected tumor mass. Wide resection margins were achieved in 17 cases, a minimal margin in two, and a contaminated margin in one. Radiotherapy was used in these three cases where resection margin was in doubt. There were two local recurrences in these three cases. Four patients have died of their disease, and there was one treatment related death. Overall probability of survival in this group of 20 patients has been expressed by the Kaplan-Meier method as 58%. PMID- 1884531 TI - Radiation and pagetic osteogenic sarcomas. AB - Radiation and pagetic osteogenic sarcomas should be distinguished from classical osteogenic sarcoma. Both occur in older patients with significantly greater comorbidity. Roentgenographically, radiation osteogenic sarcoma is typically sclerotic, whereas pagetic osteogenic sarcoma is lytic and associated with pathologic fracture. Radical resections give the best result, local control, and survival. Chemotherapy has not proven effective to date. Improvements in tumor imaging and more intensive chemotherapy regimens may permit limb-sparing surgery. Overall results remain poor, with approximately 15% five-year survival in each condition. PMID- 1884532 TI - Telangiectatic osteosarcoma. AB - Telangiectatic osteosarcoma is a rare variant of osteosarcoma. In the original report from the authors' institution, a poor prognosis was noted. The authors have updated their experience with this entity. The prognosis for patients with telangiectatic osteosarcoma has improved remarkably. The prognosis in the present series seems to be the same as that for conventional osteosarcoma. Adjuvant chemotherapy seems to help in salvaging patients with metastatic disease. However, in this small series, survival of patients without metastasis is apparently not influenced by whether they received chemotherapy. PMID- 1884533 TI - Surface osteosarcoma. AB - Osteosarcoma arising on the periosteal aspect of bone comprises a biologically heterogeneous group of neoplasms. The group as a whole may be referred to by a single descriptive term that emphasizes their common site of origin and underscores their malignant osteogenic potential: surface osteosarcoma. Its biologic heterogeneity may be approached via a number of avenues. Detailed description of individual tumors and grading are frequently employed. However, implementation of a classification system based upon reproducible clinical, roentgenographic, macroscopic, and histologic parameters is advantageous. The suggested classification system serves to clearly define parosteal and periosteal osteosarcoma, as well as recognize unusual variants. Most important, it defines therapeutic strategy. The classification system identifies low-grade, biologically indolent forms (i.e., parosteal osteosarcoma and periosteal osteosarcoma) that are best treated by surgery alone. At the same time, it recognizes high-grade forms with significant potential for life-threatening behavior (i.e., 'dedifferentiated' parosteal osteosarcoma and high-grade surface osteosarcoma) that are best managed by multimodality therapy incorporating chemotherapy and surgery. PMID- 1884534 TI - Pelvic osteosarcoma. Resection, reconstruction, local control, and survival statistics. AB - Nine patients with a malignant tumor in the periacetabular region of the pelvis were treated with a Type IIC resection and were reconstructed using a cementless, adaptable prosthetic system. In two patients, a new planning strategy was applied using three-dimensional reconstruction. There were two chondrosarcomas, three Ewing-sarcomas, two osteosarcomas, and two metastases of thyroid cancer. Excision was wide, marginal, and intralesional in three cases each. Ages ranged from eight to 68 years (average, 40 years), and follow-up periods ranged from 12 to 36 months with an average of 27 months. Overall functional evaluation was good in five cases, fair in three, and poor in one. Four patients died of local recurrences and lung metastases; all of them had marginal or intralesional resections. Histologic analysis of one retrieved specimen revealed bone ingrowth with connective tissue interface. Three-dimensional planning has proven to be a very valuable tool for achieving an anatomic reconstruction of the pelvic ring. These results are encouraging and endorse the authors to continue with the current approach of prosthetic reconstruction following Type IIC resections. PMID- 1884535 TI - Intraarterial cisplatin in the management of stage IIB osteosarcoma in the pediatric and adolescent age group. AB - Sixty patients with extremity osteosarcoma were treated with intraarterial cisplatin. This was followed by surgical resection (amputation or limb salvage) and postoperative adjuvant chemotherapy utilizing two different protocols. Seventy-five percent of patients achieved an initial response. Overall disease free survival was 58%. The number of patients treated with limb-salvage surgery gradually increased to the extent that 80% of newly-registered patients achieved a response and were subjected to limb salvage. Disease-free survival was 48% in amputation and 68% in limb salvage. The only factors found to have prognostic significance in determining disease-free survival were extent of tumor destruction induced by preoperative chemotherapy and tumor size. PMID- 1884536 TI - Comparative aspects of osteosarcoma. Dog versus man. AB - Canine osteosarcoma bears striking resemblance to osteosarcoma in humans. Similarities include the following: male sex predilection, large patient size, 75% or more affecting the appendicular site, metaphyseal location, generally unknown etiology, less than 10% of patients have documented metastasis at presentation, over 90% of tumors show high-grade histology, 75% of tumors show aneuploidy, the metastatic rate is 80% or more with amputation alone, the lung is the most common site of metastasis, and there is improved survival with adjuvant chemotherapy. The major differences are age of onset, with dogs being affected in middle age; greater frequency in the dog, with over 8000 new cases per year; and time to metastasis being faster in the dog than man. Canine osteosarcoma is a readily available and highly comparable spontaneously occurring cancer that should be useful in a better understanding of the same disease in humans. PMID- 1884538 TI - The use of bone allografts for limb salvage in high-grade extremity osteosarcoma. AB - Limb preservation is increasingly being employed in the local treatment of high grade extremity osteosarcoma. Bone allografts used to reconstruct the bony defects following tumor resection offer many advantages, including joint reconstruction and incorporation of the graft to the host bone in these relatively young patients. The results of 53 patients 30 years of age or younger were assessed to determine functional outcome. Fresh-frozen allografts were employed as osteoarticular grafts, allograft-arthrodeses, allograft-prosthesis composites, or intercalary grafts. Follow-up intervals averaged 25 months (range, two to 63 months). Life-table analysis showed that the probability of a satisfactory functional result was 73% if local tumor recurrences were excluded. Complications included 16 infections, six fractures, 12 nonunions, and six unstable joints. There were five local recurrences. Eighteen grafts ultimately failed, and in six patients, this resulted in an above-knee amputation. An additional five received a second graft. The functional "end results" of the 38 patients with two or more years of follow-up examinations were 70% satisfactory in those without a local recurrence. There was no statistically significant difference in functional outcome or local or distant relapse in those patients receiving preoperative chemotherapy. The authors conclude that allografts can be used for limb reconstruction in patients with high-grade osteosarcoma who receive aggressive adjuvant chemotherapy. The functional results are comparable to other methods of reconstruction, and once incorporated by the host, offer the advantage of longevity, compared with metallic implants. PMID- 1884537 TI - Flow cytometric studies of human osteosarcoma. AB - A number of recent studies have emphasized the potential value of flow cytometry as a "marker" to assess the malignity and therefore to help predict the biologic behavior of neoplasms, including bone tumors. Using propidium iodide and a home built flow cytometer, the authors have studied the DNA distribution in 95 patients with osteosarcoma and determined the percentage of cells in diploidy, S phase, tetraploidy, and aneuploidy. Using these values and a derived one, mean DNA concentration, it was possible to demonstrate the extent of the abnormalities observed in this group of neoplasms and show their severity as compared with the normal pattern. When the data are compared against disease-free survival and total survival, correlations were noted that, although weak, suggested that some patterns were predictive of increased risk of metastasis and death. The effect of treatment could also be assessed by evaluating the pattern before and after chemotherapy and correlating these with survival. It seems likely that with some improvement in technology, flow cytometry will be of value in the future in assessing the prognosis for osteosarcoma and predicting whether treatment has been effective. PMID- 1884539 TI - Allograft prosthetic composite arthroplasty for osteosarcoma and other aggressive bone tumors. AB - Allograft prosthetic composite arthroplasty is a reconstruction alternative after limb salvage for aggressive bone tumors. It combines an off-the-shelf implant with a fresh-frozen allograft and has several potential advantages over conventional techniques. Good clinical results can be achieved with acceptable morbidity. The procedure can be performed successfully even in patients receiving chemotherapy. Nonunion was the most common complication encountered but was amenable to autogenous iliac bone graft. The procedure can be customized to meet the needs of the patient, making custom implant manufacturing delay and expense unnecessary. PMID- 1884540 TI - Newest knowledge of osteosarcoma. PMID- 1884541 TI - Endoprosthetic replacement for stage IIB osteosarcoma. AB - Over an eight-year period, 100 patients with IIB osteosarcoma have been managed. Eighty-one were treated with limb-salvage procedures, 78 of which involved reconstruction utilizing endoprostheses. Only 19 patients received amputation as the primary treatment for local control. Since 1984, all patients received preoperative and post-operative adjuvant chemotherapy. Those patients who received chemotherapy had a statistically significant improvement in five-year survival over those who did not (57% and 32%, respectively, p = 0.014). The functional results were good overall, with excellent results seen in distal femoral reconstruction. Twenty-eight of the 78 patients treated with endoprosthetic reconstruction experienced 30 complications (36%). Mechanical failure was the most common complication (10%) but was generally correctable. The local recurrence rate was 5% and the infection rate was 3%. Local complications were manageable. A statistical analysis revealed that the relative risk of patient death was 2.5 times higher than prosthesis failure for the 78 patients with endoprosthetic reconstruction. The intermediate-term results, with a median follow-up period of 43 months, remains encouraging. PMID- 1884542 TI - Impact of two cycles of preoperative chemotherapy with intraarterial cisplatin and intravenous doxorubicin on the choice of surgical procedure for high-grade bone sarcomas of the extremities. AB - The authors assessed the impact of two cycles of preoperative chemotherapy (POCT) with intraarterial cisplatin (120 mg/m2) and continuous intravenous doxorubicin hydrochloride (Adriamycin; 20 mg/m2/day x 3 days) on the decision to perform a limb-sparing procedure (LSP) or amputation in 22 patients with high-grade bone sarcomas of the extremities. The tumor types were osteosarcoma (17), malignant fibrous histiocytoma (three), leiomyosarcoma (one), and malignant schwannoma (one). Surgical stages were IIA (three), IIB (17), and IIIB (two). The prechemotherapy surgical options chosen were 12 amputations (55% of patients) and ten LSPs (45%). The initial decisions to amputate were based on a combination of the following: improper biopsy (five cases), large tumors (ten) and those with neurovascular encroachment (six), and pathological fracture (one). Following chemotherapy, 18 LSPs (81%) and four amputations (19%) were performed. Nine of 12 patients (75%) initially deemed unresectable were converted to LSP. The median tumor response (necrosis; range, 0%-100%) was 70%; ten of 22 specimens had necrosis greater than 95%. Median tumor necrosis for the patients treated by amputation and LSPs was 45% and 88%, respectively. Following surgery, all patients received four additional cycles of cisplatin and doxorubicin. The median follow-up period is 30 months; six patients have developed metastatic disease, with a median disease-free interval of 16.6 months. The rate of local tumor control is 95% (21 of 22 patients).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1884543 TI - Experience with multiagent chemotherapy for osteosarcoma. Improved outcome. AB - Clinical researches at the authors' institution have been treating patients with osteosarcoma with effective adjuvant chemotherapy for 18 years, including 14 years experience with limb-salvage surgery. The outlook for patients with nonmetastatic high-grade osteosarcoma has improved dramatically since 1972. Updated results of the single-agent adjuvant (postoperative) chemotherapy trial project a five-year disease-free survival (DFS) of 42% (95% confidence interval [CI], 14% to 70%) with follow-up periods of 5.7 to 13.8 years compared to a two year DFS of 78% (60% to 95%) and follow-up periods of 0.6 to 6.8 years with six agent, alternating, adjuvant postoperative chemotherapy. Additionally, since limb salvage surgery began to be offered in 1976 to selected patients, 36 of 74 patients (49%) have had limb-salvage operations performed. The two-year DFS is 69% (52% to 85%) for patients having limb-salvage operations with follow-up periods of 0.6 to 10.3 years compared to 72% (57% to 87%) for amputees with follow-up periods of 0.3 to 10.3 years. It is concluded that patients receiving limb-salvage operations appear to be at no greater risk for relapse than patients receiving cross-bone amputation and that the administration of alternating, multiagent, adjuvant chemotherapy has significantly improved the DFS for patients who present with nonmetastatic high-grade osteosarcoma. PMID- 1884544 TI - Limb-sparing surgery in skeletally immature patients with osteosarcoma. The use of an expandable prosthesis. AB - Limb-sparing surgery has a definite role in the treatment of osteosarcoma in children. Increased survival, however, raises problems of limb-length discrepancy and prosthetic longevity. The concept of an expandable adjustable prosthesis addresses the problem of leg-length discrepancy. The problem of prosthesis longevity will require further long-term evaluation of current designs and methods of fixation, as well as the development of a permanent prosthesis or biologic replacement. At skeletal maturity, the expandable prosthesis may either be maintained or substituted with another implant or biological alternative if warranted by the clinical situation. PMID- 1884545 TI - Rotationplasty as a reconstructive operation after tumor resection. AB - Reconstruction in the skeletally immature patient following resection of osteosarcoma about the knee is a challenging problem. Salvaging of the limb with allogeneic or prosthetic replacement results in a shortened limb with functional limitations. Arthrodesis yields a stiff and shortened limb. The so-called growing prosthesis has a high complication rate and is still unproven. However, rotationplasty has been successfully used as a reconstructive technique following resection of these types of tumors in the skeletally immature patient. A limb with normal sensation and proprioceptions, adequate range of motion, and without leg-length discrepancies, functional limitations, or painful neuroma is to be expected. Although a prosthesis must be worn, these patients are active and participate in unrestricted physical activity. Cosmetic acceptance has not been a problem and complications are minimal. Thus, rotationplasty requires only a single operation and results in a highly functional limb. PMID- 1884547 TI - Diagnostic imaging of osteosarcoma. AB - The diagnosis, treatment planning, and follow-up evaluation of osteosarcoma rely heavily on a variety of imaging techniques. Plain roentgenography, radionuclide bone scanning, computed tomography, and magnetic resonance imaging play important roles in defining local tumor extent, detecting metastatic disease, and monitoring for recurrent tumor. Invasive studies such as angiography are now rarely necessary. In the future, newer imaging modalities, including positron emission tomography, can be expected to become important tools for evaluation of these tumors. PMID- 1884546 TI - A new approach to the resection of pulmonary osteosarcoma metastases. Results of aggressive metastasectomy. AB - Pulmonary metastases are the primary cause of death from bone and soft-tissue sarcoma. Recognition that even multiple resections of metastases can improve survival has led to a more aggressive surgical approach to these patients. The authors instituted an aggressive approach and a new technique and retrospectively analyzed the results of multiple, pulmonary metastasectomies for pulmonary metastases in 34 patients, 21 of whom had osteogenic sarcoma (OGS). A number of cases were referred from other institutions, where they had been considered inoperable because of extensive or recurrent disease. Using lateral thoracotomies, laser technique with minimal parenchymal excision, and thin gloves for palpation, aggressive metastectomy was carried out. A mean of 3.1 thoracotomies were performed, with an average of 10.6 nodules resected per thoracotomy. Operative morbidity and mortality were minimal. Evaluation of potential prognostic factors revealed no statistically significant survival difference on the basis of disease-free interval (DFI), number of nodules resected, number of thoracotomies, or size of largest nodule resected. There was a clear trend toward decreased survival of patients with larger nodules (greater than 2 cm), but because of the small number of patients in this group, no firm conclusions can be drawn. Five-year survival was 49% for the study group as a whole, and 39% for the OGS patients. Aggressive surgical resection of pulmonary metastases from bone and soft-tissue sarcoma should be considered when there is control of local disease, no evidence of extrapulmonary metastasis, and adequate postresection pulmonary reserve. The presence of bilateral, extensive, or recurrent disease is not a contraindication to thoracotomy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1884548 TI - Limb salvage for osteosarcoma in the 1980s. AB - The incidence of local recurrences following limb salvage performed by experienced surgeons with wide surgical margins and with the use of neoadjuvant chemotherapy is sufficiently low (5%-10%) so as not to have a biologically statistically significant impact on the long-term survival rate. Following limb salvage, the incidence of morbidity increases with a few patients occasionally requiring prolonged or repeated hospitalizations and further surgical procedures, even amputation. The durability of the reconstructions is variable, and many of the mobile knee reconstructions may need to be revised if the patients become long-term survivors. The function of salvaged limbs is better than that after the alternative amputation, but none of the reconstructions will give normal function. Finally, no matter which type of surgery on the lower extremity is selected, patients will have a good early psychosocial adjustment if no premorbid psychosocial disorder is present. PMID- 1884549 TI - Involvement of the retinoblastoma gene in primary osteosarcomas and other bone and soft-tissue tumors. AB - The retinoblastoma (Rb) gene, thought by some to be associated with tumor formation of retinoblastoma as a recessive human oncogene, was investigated in 57 cases using DNA and RNA from primary osteosarcomas and other bone and soft-tissue tumors. Eight of 23 osteosarcoma cases (35%) showed structural alterations of the Rb gene. Three of the eight demonstrated homozygous deletions, and the remaining five cases showed heterozygous deletions. Seven out of eight cases represented deletion of a 7.5-kb HindIII fragment. Northern blot analysis of five cases of osteosarcoma showed that four demonstrated no detectable Rb gene transcription, and one case had a truncated 3.5-kb fragment with a faint 4.7-kb band. In the other 34 cases of bone and soft-tissue tumors, two cases of three malignant fibrous histiocytomas showed an Rb gene abnormality by Southern blot analysis. These results strongly suggest that Rb gene alteration is pertinent to the tumorigenesis of most osteosarcoma cases and some other bone and soft-tissue tumors. PMID- 1884550 TI - A longitudinal study of growth velocity and development of secondary gender characteristics versus onset of idiopathic scoliosis. AB - This study focused on evaluating the impact of the adolescent growth spurt on the onset of idiopathic scoliosis. A total of 698 students (362 girls and 336 boys aged nine to 12 years) were followed for three years to study their growth in the pubertal period and changes in spinal status. Every six months measurements were taken of body height and the development of secondary gender characteristics was recorded. The onset of the adolescent growth spurt could thus be detected in each child. When children with and without scoliosis were compared, it became evident that scoliotic children grew faster. Girls whose scoliosis developed from a previously normal body posture showed a peak height velocity (PHV) of 8.1 cm per year, whereas girls with a normal body posture throughout the pubertal stage had a PHV of 7.1 cm per year. The most rapid growth spurt was observed in Stages 2 and 3 of breast and pubic hair development. Simultaneously, the most frequent spinal status changes occurred in Stages 2 and 3 of sexual maturity; they were twice as frequent as in Stage 1 and four times as frequent as in Stages 4 and 5. Students in whom scoliosis developed in puberty during the adolescent growth spurt grew faster than their peers who did not develop scoliosis, which need not imply that they will eventually be taller after growth is completed. PMID- 1884551 TI - Pseudoaneurysm of the popliteal artery as a complication of an osteochondroma. A review of the literature and a case report. AB - False aneurysm of the femoral artery was associated with a solitary osteochondroma of the femur in a 22-year-old man. An extensive review of the literature and the problems related to diagnosis revealed that the aneurysm was apparently unique. Contrary to previous reports, computed tomography and angiography did not establish the diagnosis. The physical findings were more informative. PMID- 1884552 TI - The use of methylmethacrylate in primary total knee replacements with large tibial defects. AB - Bone defects in the tibial plateau present technical problems in primary knee replacement surgery. A variety of techniques is available to solve these problems. Of 59 patients treated with a cement fill and followed an average of 7.1 years (range, five to 11 years), there was only one failure requiring revision. Overall, knee scores averaged 78 points and roentgenogram scores averaged 85 points. Radiolucent lines were noted in 43 of the 59 patients, but none were progressive except in the one failure. There was no clinical correlation between the presence of radiolucent lines and clinical symptoms. Good long-term results might be expected from the cement fill when the bone defects are smaller than 20 mm and affect less than 50% of either plateau. PMID- 1884553 TI - Risk factors influencing mortality after bipolar hemiarthroplasty in the treatment of fracture of the femoral neck. AB - The hospital records of 204 patients (mean age 80 years, range 54-96 years) with a displaced intracapsular femoral neck fracture treated by cemented bipolar hemiarthroplasty were examined to record all available data on factors suspected of influencing mortality. The data were analyzed statistically using survival analysis (Cox model). The six months mortality rate was 20% and the one year mortality rate was 28%. The following factors, in order to decreasing importance, had significant influence on mortality: cardiac factors other than previous myocardial infarction; status as a nursing home patient; chronic pulmonary disease; serum creatinine level greater than 1.7 mg/100 ml; pneumonia; previous myocardial infarction; duration of surgery; and gender. The following factors had no significant influence on mortality: age, time delay from admission to surgery, mode of anesthesia, and cerebrovascular diseases. In conclusion, medical conditions were the most important determinants of survival in the present study. The time delay between admission and surgery did not influence the chances of survival. This does not mean that surgical delay beyond that essential for stabilizing the patient is not problematic, but indicates that ample time should be spent on assessment and resuscitation before surgery. PMID- 1884554 TI - A pneumatic leg brace for the treatment of tibial stress fractures. AB - Forty-two competitive athletes with posterior medial pain in the lower one-half of the tibia were evaluated by plain roentgenograms and bone scans. Twenty stress fractures were diagnosed in 17 patients by plain roentgenograms or bone scans or both. The remaining 25 patients were diagnosed as having shin splints. All 42 patients subsequently had a pneumatic leg brace applied to the affected limb or limbs. The 17 patients with stress fractures were able to ambulate without pain and were allowed to resume light training in an average of one week. Their injuries were nontender to palpation. The patients were allowed to resume intensive training at an average of 3.7 weeks postinjury. Patients returned to competition at the preinjury level in an average of 5.3 weeks after application of the brace. The pneumatic leg brace allowed the athletes with tibial stress fractures to begin pain-free ambulation and rehabilitation, thus facilitating the maintenance of their cardiovascular fitness and permitting an early return to competition. PMID- 1884555 TI - Nonspecific findings on MR imaging. The importance of correlative studies and clinical information. AB - Although magnetic resonance (MR) imaging is highly sensitive for the detection of abnormalities of the musculoskeletal system, changes in marrow and soft-tissue signal intensity are often nonspecific, and benign conditions may be mistaken for malignancy. In an effort to identify the cause of this type of misdiagnosis in MR examinations, the MR scans were reviewed of 30 patients whose images manifested bone and/or soft-tissue changes that were initially believed to be consistent with malignancy but were later found to represent benign conditions. Of the 30 patients, MR abnormalities were attributable to trauma in 11, benign tumors and tumorlike conditions in ten, infection in seven, and prior radiotherapy in two. In 24 cases, correlative imaging studies (14 patients), appropriate clinical history (six patients), and/or physical and laboratory examinations (four patients) would have avoided these misdiagnoses. PMID- 1884556 TI - Recent advances in the chemotherapy of metastatic osteogenic sarcoma. 1972. PMID- 1884558 TI - A review of 13-years experience of osteosarcoma. AB - Since the inception of the authors' facility, 365 patients with osteogenic sarcoma have been treated. While other facilities were surgically treating patients with primary amputation, this facility attempted limb-salvage surgery. The majority of patients being treated with limb-salvage surgery had the resected bone replaced by a metallic endoprosthetic replacement. The emphasis on conservative surgery led to the development of growing endoprosthetic replacements with the first being used in 1975. The cumulative survival of those patients with Stage 2 osteosarcoma treated at this facility between 1977 and 1984 is 48% at five years. PMID- 1884557 TI - The management of IIB osteosarcoma. Experience from 1976 to 1985. AB - From 1976 to 1985, 75 IIB osteosarcomas have been treated out of a total of 98 osteosarcomas at the authors' institution. Because of the effective chemotherapy including high-dose methotrexate administered during this time period, the surgical management changed, and only ten patients out of the 75 IIB osteosarcomas required an amputation. The overall result of 76.7% of disease free, three-year survival was equally distributed regardless of the surgical procedure. Endoprosthesis, resection with or without grafts, and rotationplasties, as well as amputations, revealed similar results. No negative influence from the limb-sparing surgery could be observed. PMID- 1884559 TI - Management of osteogenic sarcoma in children and adolescents. AB - The management of osteogenic sarcoma in children has made a fantastic step on the survival rate, but there still remains unexpected late metastatic recurrence even in initially good responders to chemotherapy and lower survival rate in the bad responder group. Therefore, the research on etiology and on the understanding and rating of oncologic power of the tumoral cells as well as other kinds of treatment (vaccine, immunotherapy, and other types of chemotherapy) must be increased. The initial function after replacement is good and is often excellent but increasing deterioration is noticed during each follow-up evaluation. A considerable effort is still to be done for bone and joint replacement. Biocompatible material with mechanical strength and resistance to wear will be used for a long time because of the young age of the patients. There must be better use and understanding of the allograft revascularization, as well as a better biologic connection between the bone host and replacement device. This will probably be used in the future with less cement and more of a modular system. The final prognosis will remain for a long time in the perfect cooperation between the various members of the teams (oncologist, surgeon, imager, pathologist, and research team) who treat the patients. PMID- 1884560 TI - IIB osteosarcoma. Current management, local control, and survival statistics--Sao Paulo, Brazil. AB - Ninety-two patients with IIB osteosarcoma of the extremities were treated with intraarterial (IA) cisplatinum (CDDP) followed by surgery [amputation (61.6%) or resection with endoprosthesis (38.4%)]. Postoperative chemotherapy alternating adriamycin and CDDP was used. The total three-year survival was 62.1%, and the disease-free survival was 41.1%. The pathologic evaluation of the degree of tumor necrosis in response to the IA CDDP showed that in 53.2%, the necrosis was over 90%. The multivariate analysis of prognostic factors has shown that the highest survival was among females with tumors smaller than 15 cm. Patients with lesions equal to or larger than 15 cm were three times as likely to die of the disease. A second, more aggressive study is now underway, in which high dose methotrexate (HDMTX) is preoperatively combined with adriamycin and CDDP. Following operation, ifosfamide is added to the cases with a smaller degree of tumor necrosis, while the other group of patients will continue with HDMTX, in addition to CDDP and adriamycin (these last two drugs are used in both arms). Until now, complete remission has been achieved in 82% and 86%, respectively, with a follow-up examination varying from four to 26 months (average, 14 months). This is of extreme importance, because the majority of the authors' patients have tumors at initial evaluation larger than 10 cm in diameter. PMID- 1884561 TI - IIB osteosarcoma. Current management, local control, and survival statistics--The Netherlands. AB - Guarded optimism is justified in light of the results of treatment of IIB osteosarcoma in the Netherlands. This is due to improvements in diagnostic imaging techniques, staging, adjuvant chemotherapy, and surgical treatment. Five year survival rates have increased from 25% to 80%. En bloc resection is currently possible. This makes reconstructive procedure justified, both from an oncologic and orthopedic view. Many questions are still unanswered, concerning evaluation of tumor necrosis because of chemotherapy, optimal adjuvant therapy, functional evaluation of different types of reconstruction, and psychological development of the patient. An international gathering of data on the overall treatment of IIB osteosarcoma is advocated to find answers on the above-mentioned questions. A noninvasive adjustable-lengthening prosthesis is mentioned as a Dutch solution to leg-length discrepancy. This prosthesis can be used after limb saving surgery in young children. PMID- 1884562 TI - Current management, local management, and survival statistics of high-grade osteosarcoma. Experience in Japan. AB - To report the current management of high-grade osteosarcoma in Japan, the authors studied the results of 55 cases treated in the authors' institutions and data provided by Osaka University (59 cases), Chiba Oncology Group (97), and Sapporo National Hospital (70). Twenty-five of the 55 cases in the authors' series were treated by limb-salvage surgery, 27 by amputation, and the remainder by chemotherapy. In all 226 cases from the three institutes, 106 were treated by amputation and 120 by limb-salvage surgery. Two local recurrences (4%) were found in the authors' series, three in the Osaka series, and eight in the Chiba series. Five-year accumulative survival rates in this study showed some differences, depending upon the institution or upon the protocol employed: in the authors' series it was 60% overall and 68% for a stronger chemotherapy group; in the Osaka series, it was 50% in a mild chemotherapy group and 72% in an intensive chemotherapy group; and in the Sapporo series, it was 36% and 73%, respectively. This study showed that local control of IIB osteosarcoma was successfully achieved by preoperative adjuvant chemotherapy and wide resection, and that an intensive chemotherapeutic combination of high-dose methotrexate, cisplatinum, and doxorubicin is promising. PMID- 1884563 TI - Adjuvant chemotherapy of high-grade osteosarcoma of the extremity. Updated results of the Multi-Institutional Osteosarcoma Study. AB - The Multi-Institutional Osteosarcoma Study (MIOS) was designed to determine whether intensive multiagent adjuvant chemotherapy improves the outcome of patients with nonmetastatic high-grade osteosarcoma of the extremity as compared with concurrent controls. After definitive surgery of the primary tumor, patients were randomly assigned to immediate adjuvant chemotherapy or to observation without adjuvant treatment. Updated results of this trial indicate that the projected six-year event-free survival for the control group is 11% compared to 61% for the chemotherapy group (p less than 0.001). Similar results were observed in patients who declined randomization but who were followed according to the treatment arms of the protocol. When randomized and nonrandomized patients are pooled according to assigned treatment, a survival advantage favoring those patients treated with immediate adjuvant chemotherapy is apparent. An analysis of prognostic factors among patients receiving immediate adjuvant chemotherapy reveals that elevation of the serum lactic dehydrogenase at diagnosis is the factor most predictive of adverse outcome. Location of the primary site in the tibia confers a favorable prognosis. The authors conclude that the natural history of high-grade osteosarcoma of the extremity has not changed over the past two decades. The administration of immediate adjuvant chemotherapy has a significant favorable impact on event-free survival and should be recommended for all such patients. PMID- 1884564 TI - Neoadjuvant chemotherapy for nonmetastatic osteosarcoma of the extremities. AB - Between September 1986 and December 1988, 125 patients with osteosarcoma of the extremities entered the second neoadjuvant study at the authors' institution. Patients received preoperatively two cycles of methotrexate (MTX) intravenously, followed by cisplatinum (CDP) intraarterially, plus adriamycin (ADM) intravenously. After surgery, the patients classified as "good responders" (more than 90% tumor necrosis) received ADM, MTX, and CDP, while the "poor responders" (less than 90% tumor necrosis) had a longer chemotherapy that included ifosfamide and etoposide (VP-16) in addition to MTX, ADM, and CDP. Limb salvage was possible in 85% of patients, 8% had an amputation, and 7% had a rotationplasty. The surgical margins were adequate (radical or wide) in 88% of cases and inadequate (marginal or intralesional) in 12%. At an average follow-up period of 28 months (range, 13 to 41), 109 patients (87%) remained continuously disease free, 15 (12%) relapsed with pulmonary metastases, and one patient (0.8%) had a local recurrence. Compared with the first neoadjuvant study at the authors' institution that used only MTX and CDP preoperatively, the percentage of limb salvages, "good responders," and continuously disease-free survival at two years was significantly higher in the second Rizzoli neoadjuvant study (85%, 74%, and 87% versus 77%, 52%, and 59%). Systemic toxicity because of chemotherapy was superimposable. A retrospective analysis of the real dose intensity for each patient demonstrated a correlation between the intensity of chemotherapy and prognosis. PMID- 1884565 TI - Telangiectatic osteogenic sarcoma of the extremities. Results in 17 patients treated with neoadjuvant chemotherapy. AB - Seventeen patients with telangiectatic osteogenic sarcoma (TOS) of the extremities were treated with neoadjuvant chemotherapy, according to two different protocols. Preoperatively, the patients received high-dose methotrexate (HD-MTX) and cisplatinum (CPD) (HD-MTX/CPD) and doxorubicin. CPD was delivered intraarterially, the other drugs intravenously. Limb-salvage surgery was performed in 12 instances, and five patients were treated with amputation. Postoperative chemotherapy was tailored according to the grade of chemotherapy induced necrosis. In 13 cases (86%), the resultant grade of necrosis was greater than 90% (good responders). The mean follow-up interval was 3.5 years with a range of 18 to 78 months. Fourteen patients (82%) remained continuously disease free, while three patients developed lung metastases. Two of these died because of uncontrolled disease, whereas the third patient is alive and disease-free after metastasectomy. No local recurrences were observed. These results are better than those observed in 215 contemporary cases of conventional osteosarcoma treated with the same protocols. This study confirms that TOS is not a uniformly lethal tumor as suggested by prior reports. By employing neoadjuvant chemotherapy, a high percentage of patients with TOS can be cured, and in most of them, a limb-sparing surgery is possible and safe. PMID- 1884568 TI - Ajmaline test in a patient with chronic renal failure. A pharmacokinetic and pharmacodynamic study. AB - Pharmacokinetic and pharmacodynamic properties were studied after intravenous administration of ajmaline 1 mg/kg in an anuric patient, who underwent the electrophysiological ajmaline test. The magnitude and rate of onset of the typical electrophysiological effects of ajmaline (prolongation in atrio-Hisian and His-ventriculum conduction times) were within the range of normal values. The plasma concentration curve showed a triexponential decay with half-lives as follows: initial phase (t1/2 alpha) 1.34 min, fast elimination phase (t1/2 beta) 10.13 min and terminal (slow) phase (t1/2 gamma) 258.6 min. Other relevant pharmacokinetic parameters calculated were: total plasma clearance 45.91 L/h; volume of distribution 285.6L; protein binding 47%. Five hours after administration the patient underwent a 3.5h haemodialysis without any substantial increase in the slope of the final elimination phase of the curve. A major problem in interpreting the pharmacokinetic results is the lack of reliable reference data in healthy subjects. It is likely that the ajmaline t1/2 reported in the literature (13.4 min) does not reflect the true terminal t1/2 of the drug, because it was determined during an unduly short sampling period (30 min). Nevertheless, if we compare just the first 30 min of the concentration-time curves, our results are nearly superimposable on those found in healthy subjects. PMID- 1884566 TI - Pharmacokinetics of rectal drug administration, Part II. Clinical applications of peripherally acting drugs, and conclusions. AB - Part I of this article, which appeared in the previous issue of the Journal, covered general considerations, the physiology of the rectum, spreading of drugs into the colon, rectal absorption, partial avoidance of first-pass elimination, rate-controlled rectal delivery of drugs, irritation of the rectal mucosa and clinical applications of rectal administration, and discussed centrally acting drugs. In Part II, this discussion is extended to drugs which act peripherally and to methods of enhancing rectal drug absorption. The overall summary appeared in Part I. PMID- 1884567 TI - Clinical pharmacokinetics of drugs used in juvenile arthritis. AB - Juvenile arthritis is defined as the occurrence of objective evidence of arthritis for a minimum of 6 weeks, in a child 16 years of age or younger. With a reported incidence of 9 to 19.6 per 100,000 children, juvenile arthritis is considered to be a rare disease. There is no known cure; however, up to 75% of patients will undergo remission by late adolescence. Drugs used in the treatment of juvenile arthritis are divided into 2 major classes: (a) the nonsteroidal anti inflammatory drugs (NSAIDs) including salicylates, naproxen, ibuprofen, fenoprofen, ketoprofen, flurbiprofen, indomethacin, sulindac, tolmetin and diclofenac, and (b) disease modifying agents which encompass drugs such as antimalarial agents, gold, methotrexate, penicillamine and sulfasalazine. In almost all the reports dealing with the pharmacokinetics of NSAIDs, the level of disease activity has not been noted. The level of activity is important since, during a flare, the plasma albumin may fall to the point that it causes a substantial and clinically significant increase in the unbound serum concentration of highly bound drugs. The relationship between the concentration of these drugs in the systemic circulation and their efficacy is not clear. However, for many of them, therapeutic drug monitoring is recommended as a means of reducing the possibility of toxic reactions. Further pharmacokinetic and dynamic evaluations are needed for many of these drugs in juvenile arthritis. PMID- 1884571 TI - The effect of a high consumption of citrus fruit and a mixture of other fruits on dental caries in man. AB - The purpose of this study was to determine the effect of a high intake of citrus fruit or a collection of different varieties of fruit on the caries experience in farm workers. The number of subjects included was: for the citrus-producing group 120 (55 men), for the mixed variety group 95 (49 men) and 50 (25 men) for the grain-producing group (control group). Only farms where the drinking water fluoride concentration was less than 0.10 ppm were selected for the study. The mean daily intake of added sugars (excluding that from the specific fruits to be investigated), was the highest for the control group. The percentage frequency of toothbrushing of the three different groups was comparable and low. Significant differences (p less than 0.05) in the caries experience could be demonstrated between the two age categories (15-34 yr and 35+ yr) within any one of the three groups. Significant (p less than 0.0001) differences in the mean DMFT were found between the control group and each of the fruit-producing groups. No significant differences (p greater than 0.05) could be demonstrated between the two fruit producing groups. However, the highest DMFT (24.8) was found in the citrus producing group, with less in the mixed variety fruit group (22.7) and the least in the control group (9.9). The sequence of the order of magnitude of the components (D, M, F) of the DMFT was the same as that for the caries experience as such. It is concluded that a high consumption of various fruits over a long period is associated with a high caries experience. PMID- 1884569 TI - Clinical pharmacokinetics of drug administered buccally and sublingually. PMID- 1884572 TI - Awareness and attitudes toward hepatitis B among Malaysian dentists. AB - A questionnaire was mailed to 1217 dentists whose names appear in the Dentist Register of 1987 in order to assess their awareness and acceptance of hepatitis B vaccine and their pattern of glove usage. Almost all the respondents (99.6%) were aware of the availability of the hepatitis B vaccine yet only 44.8% have received the vaccine. This is in spite of the fact that the majority (61.2%) of the vaccine non-acceptors have no reservations concerning the vaccine. About 71% and 63% of the vaccine-acceptors and non-acceptors respectively believed that the risk of their contracting hepatitis B was high or very high. About 22% of the vaccine non-acceptors never used gloves when treating patients as compared to 9% among vaccine acceptors. Overall, about 78% of the respondents have experienced needleprick injuries in the 3 years preceding the survey. PMID- 1884570 TI - Clinical pharmacokinetics and kinetic-dynamic relationships of dilevalol and labetalol. AB - Dilevalol and labetalol are examples of a growing number of new beta-blockers which combine nonselective beta-adrenoceptor antagonism with vasodilator activity. Dilevalol is one of the 4 stereoisomers of labetalol, and is estimated to form approximately 25% of the racemic drug. Labetalol itself is an alpha 1 antagonist but dilevalol, which has negligible affinity for alpha-receptors, exerts its vasodilator effect via beta 2-agonism. Both drugs are rapidly and completely absorbed in 60 to 90 min and subject to extensive first-pass hepatic metabolism; the average bioavailability after oral administration is around 20 to 35%, and there is wide interindividual variability in plasma drug concentrations and dosage requirements. The volume of distribution of dilevalol (17 to 25 L/kg) is higher than that reported for labetalol (3 to 16 L/kg), although both drugs are concentrated in the extravascular compartment. Correspondingly, the elimination half-life of dilevalol at steady-state is around 15h compared with 8h for labetalol. There is evidence that the pharmacokinetics of dilevalol change (a reduction in clearance) in translation from single-dose to long term therapy. There is no clinically significant effect of age on the steady-state disposition of either drug and the pharmacokinetics of labetalol appear to be unchanged during pregnancy. Although there is a linear relationship between dose and area under the concentration-time curve, early studies found no evidence of a simple relationship between dose or plasma drug concentration and the fall in blood pressure. However, an integrated pharmacokinetic-pharmacodynamic model has been used to correlate concentrations of both drugs with reductions in systolic and diastolic blood pressure in individuals. This approach derives a mathematical description of antihypertensive response which integrates pharmacokinetic and pharmacodynamic information and also takes account of placebo effects and changes in drug concentration and blood pressure during the dosage interval. The pharmacokinetic-pharmacodynamic relationships of labetalol are characterised by a linear model. For example, in a group of healthy volunteers, the 'responsiveness' to labetalol was -0.19mm Hg/micrograms/L. In contrast, the relationships of dilevalol are best described by a Langmuir maximum effect model, and so individual responses to short and long term treatment have been quantified by the concentration-effect parameters of maximum effect and drug concentration required to produce 50% of this.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1884573 TI - Toothbrushes with graduated wear: correlation with in vitro cleansing performance. AB - A display set of toothbrushes with graduated natural wear was shown to 268 adult respondents who were asked to indicate which brushes were "worn out." The same brushes were then compared against each other for their ability to remove artificial plaque in models of interproximal and facial surface cleansing effectiveness. Despite pronounced differences in the degree of wear among the toothbrushes, no correlation was found between visual estimation of toothbrush effectiveness and its cleansing ability in the models tested. It is possible that other variables (toothbrushing technique, force applied, manual skills) exert a greater influence on plaque removal than brush wear and explain the results of this experiment. PMID- 1884574 TI - Comparison of a phenolic and a 0.2% chlorhexidine mouthwash on the development of plaque and gingivitis. AB - Chlorhexidine and phenolic mouthrinses have attracted considerable interest as adjuncts to oral hygiene. The aim of this study was to compare two well known proprietary mouthrinse products for their effects on plaque regrowth, the development of gingivitis and the formation of toothstaining. The study was a single-blind, randomized, placebo-controlled, triple cross-over experimental, gingivitis design. A group of 15 volunteers with a very high standard of oral hygiene and gingival health used each rinse for 19 days in the absence of normal toothcleaning. Each period was separated by a 21 day washout. Plaque scores were significantly different between the rinses, being lowest with chlorhexidine and highest with saline. The plaque area increased 3-fold with the phenolic rinse and 6-fold with the saline rinse compared to the chlorhexidine rinse. Similarly, gingivitis increments were lowest with chlorhexidine and highest with saline but differences between rinses did not reach significance. Staining was significantly different between rinses, primarily due to minimal staining associated with the saline rinse. Staining occurred with both the chlorhexidine and phenolic mouthrinses. It is concluded that the 0.2% chlorhexidine rinse offers greater oral hygiene benefits than the phenolic rinse. The question of indications and durations of use of mouthwash products should be addressed. PMID- 1884575 TI - The radio-opacity of fishbones--species variation. AB - Plain radiographs are often taken to localize fishbones which lodge in the oropharynx and hypopharynx, but which are not seen on clinical examination. Fishbones which are thus revealed can then be removed by endoscopy. For a lateral neck radiograph to be useful in excluding a fishbone when mirror examination is difficult or fails to reveal a foreign body, it is important to know which types of fishbone are radio-opaque. We used a pig's neck preparation to simulate a human neck to determine the radio-opacity of the bones of 14 different species of fish eaten in the British Isles. We conclude that only the bones from cod, haddock, cole fish, gurnard, lemon sole, monk fish, grey mullet and red snapper are well seen by soft tissue radiographic techniques. PMID- 1884576 TI - Current working practices during pregnancy in British radiologists. AB - A postal survey was conducted of female radiologists practising in the United Kingdom to assess attitudes to, and working practices during, pregnancy in radiologists. A wide variation was found in both practices and attitudes but with a good general appreciation of the principles of radiation protection. The risk to the fetus of occupational exposure during pregnancy is likely to be small but there is a widespread desire for more guidance on suitable and safe working practices for pregnant radiologists. PMID- 1884577 TI - Technical report: evacuating proctography--a simplified technique. AB - We describe a prospective study of 63 patients with proctological symptoms, comparing the radiological findings when performing evaluating proctography in both the sitting and left lateral positions. We found that although the left lateral method was slightly less sensitive, the abnormalities missed represented only minor early changes and were of no clinical significance. We conclude that the technique we have described could be adopted easily as a screening procedure for patients with unexplained anorectal symptoms. PMID- 1884578 TI - Case report: splenic-gonadal fusion--the ultrasound appearances. AB - We report the ultrasound appearances, with pathological correlation, of splenic gonadal fusion in a patient who presented with an asymptomatic scrotal swelling. Ultrasound examination showed an echo-poor 2 cm diameter lesion in the upper pole of the left testicle. Histologically the lesion was normal spleen. Splenic gonadal fusion should be considered in the differential diagnosis of scrotal swellings. PMID- 1884579 TI - Case report: in-utero aspiration of sacrococcygeal cyst. AB - Pre-natal aspiration, under ultrasound control, was performed on a sacrococcygeal cyst measuring 19 cm in diameter in a 38 week fetus to allow normal vaginal delivery of a live baby girl. This is the first report of such intervention leading to normal delivery. PMID- 1884580 TI - Case report: antenatal diagnosis of congenital glioblastoma. AB - We report a case of congenital cerebral glioblastoma. The initial antenatal ultrasound scan showed a peripheral area of high reflectivity within the right cerebral hemisphere. A subsequent scan showed that the area of high reflectivity had increased in size to completely fill the hemisphere, with shift of the falx and contralateral ventriculomegaly. Glioblastoma is one of the least common congenital brain tumours and has the poorest prognosis with no recorded cases surviving beyond one year. PMID- 1884581 TI - Case report: primary systemic amyloidosis presenting as breast masses, mammographically simulating carcinoma. AB - A case of primary systemic amyloidosis presenting as bilateral breast masses is described. The mammographic appearance was of multiple ill-defined masses associated with clustered microcalcifications simulating carcinoma. This is the first case of amyloid of breast reported in the radiological literature. Other available literature of breast involvement in systemic amyloidosis is reviewed. PMID- 1884582 TI - Case report: uncommon radiological and pathological features of giant colonic diverticula. AB - A case of multiple giant sigmoid diverticula is described in which a barium enema revealed two giant diverticula communicating with the sigmoid lumen. Both diverticula were located on the mesenteric border of the sigmoid colon, and histologic examination showed mucosal and serosal layers with no evidence of smooth muscle. The pathogenesis, pathology, radiological manifestations and differential diagnosis of this rare condition are discussed. PMID- 1884583 TI - Case report: unilateral hydronephrosis following obstruction of the inferior vena cava by tumour thrombus. AB - Venous compression of the ureter is a rare cause of hydronephrosis. We report a case where invasion of the inferior vena cava by a renal carcinoma led to dilation of the ovarian vein and ureteric obstruction. PMID- 1884584 TI - Case report: therapeutic embolization to control haematuria from transitional cell carcinoma of the kidney. AB - A 66-year-old man presented with myocardial infarction precipitated by anaemia secondary to chronic haematuria from transitional cell carcinoma of the renal pelvis. Haematuria was controlled by therapeutic embolization of the renal artery until elective nephrectomy could be performed. PMID- 1884585 TI - Case report: severe adverse reaction to oral Iohexol. AB - A patient developed a severe adverse reaction following oral administration of Iohexol given for a follow-through examination. This has not been described previously. PMID- 1884586 TI - Critical evaluation of the radial head-capitellum view in acute elbow trauma with an effusion. PMID- 1884587 TI - A simple way to explain radiation. PMID- 1884588 TI - MRI of the cervical spine: rheumatoid arthritis compared with cervical spondylosis. AB - This study is a comparison of the cervical spine MR images from 26 patients with rheumatoid arthritis of the cervical spine with those from an age and sex matched group suffering from cervical spondylosis. Erosion of bone and major atlanto axial subluxation were confined to rheumatoid arthritis. Soft tissue changes revealed by MRI included distortion of normal ligaments and bursae around the dens, particularly in rheumatoid arthritis. Abnormal masses of soft tissue were found in both groups, but those suggesting acute inflammation were much more frequent in rheumatoid arthritis than in cervical spondylosis. Neural compression was well demonstrated, and in rheumatoid arthritis was usually caused by bony structures whereas in cervical spondylosis it was usually due to disc material. It is concluded that MRI should be used as the first investigation to follow plain films in rheumatoid arthritis of the cervical spine. Bone and soft tissue changes are clearly shown, but interpretation of the images requires the recognition that some observed abnormalities may be due to coincidental cervical spondylosis. PMID- 1884589 TI - Radiologically controlled balloon dilatation of rectal strictures. AB - Rectal stricture is a well recognized complication following anterior resection. It is traditionally managed with metal dilators or resection. This paper describes the use of balloon dilatation for benign anastomotic rectal strictures. Eight patients were included in the trial. Only one dilatation was necessary in four patients while the remaining four patients required further dilatation for relief of symptoms. The mean diameter of the stricture increased from 7.2 mm to 17.0 mm post-dilatation. There were no complications associated with the procedure. Balloon dilatation is a safe and effective method of treating benign anastomotic rectal strictures. PMID- 1884590 TI - Accuracy of CT in detecting squamous carcinoma metastases in cervical lymph nodes. AB - The accuracy of computed tomography (CT) in the assessment of nodal metastases was correlated retrospectively with the pathological examination in 28 patients with known head and neck squamous cell carcinoma, who underwent neck dissections. Three patients had bilateral neck dissections resulting in a total of 31 dissections. CT scanning correctly staged 28 of 31 neck dissections providing an accuracy of 90%, a sensitivity of 87.5% and a specificity of 100% in the detection of nodal metastases. Of the 21 true positives, underestimation of the extent of nodal disease occurred in seven cases. Regarding extracapsular nodal spread, CT resulted in an accuracy of 62%, a sensitivity of 62.5% and a specificity of 60%. All three false negatives for nodal metastases occurred in metastatic spread to the submandibular nodes. The existing criteria for assessment of nodal metastases with CT are sensitive and specific, but in the assessment of extranodal spread CT may not detect 37.5% of cases. PMID- 1884592 TI - Mammographically guided ultrasound: a new technique for assessment of impalpable breast lesions. AB - A new technique for the assessment and localization of breast lesions is described. The position of a lesion is identified mammographically using a fenestrated compression plate. This allows access for an ultrasound probe directly over the lesion. This technique has proved valuable in the assessment of breast lesions and a simple inexpensive, reliable method of localization. We give a preliminary report of our results. PMID- 1884591 TI - Bronchiectasis in hypogammaglobulinaemia--a computed tomography assessment. AB - To determine the pattern of bronchiectasis in hypogammaglobulinaemia we reviewed the CT scans of 38 hypogammaglobulinaemic patients. Twenty-two had bronchiectasis, seven had bronchial wall thickening without bronchiectasis and the remaining nine were normal. The middle lobe was the most common site of bronchiectatic involvement, followed by the lower lobes and the lingula. There were no cases of isolated upper lobe involvement. In patients who had bronchial wall thickening without bronchiectasis the middle lobe and lower lobes were again most commonly affected. It is postulated that in these hypogammaglobulinaemic patients bronchial wall thickening represents a stage of bronchial inflammation prior to the development of bronchiectasis. Patients with X-linked agammaglobulinaemia (XLA) develop bronchiectasis at a significantly earlier age than those with 'common variable' hypogammaglobulinaemia (CVH) (P = 0.02). No correlation was found between the serum levels of immunoglobulin classes at diagnosis and the subsequent development of bronchiectasis. PMID- 1884593 TI - Fibrous mastopathy in insulin dependent diabetics. AB - The cases of two poorly controlled insulin dependent diabetic women, presenting with hard discrete breast lumps clinically suspicious of carcinoma are presented. Mammography revealed dense dysplastic parenchymal changes with no specific features of carcinoma and ultrasound showed acoustic shadowing but no discrete mass. Excision biopsy of these lumps was performed. Histologically they were benign, and were composed of fibrous tissue with a chronic inflammatory cell infiltrate. With better awareness of fibrous mastopathy which can occur in this group of diabetic patients, and with the absence of specific radiological features of malignancy, some of these women may be observed and spared excision biopsy. PMID- 1884594 TI - Ultrasound of extranodal abdominal lymphoma--a review. AB - Ultrasound is a valuable method for the detection of abdominal lymph node involvement in malignant lymphoma. In this review the characteristic patterns of organ involvement with lymphoma are described, the features compared with other pathologies and the appearances correlated with histological findings. PMID- 1884595 TI - Preliminary experience with the Berger neurobiopsy device for ultrasound guided aspiration and biopsy of intracranial lesions. AB - Our preliminary experience is presented in the use of the Berger neurobiopsy device for ultrasound localization and biopsy of intracranial lesions through a burr hole. The apparatus and technique are described, along with the results of its use in the first 49 patients. In these patients 43 tumours were biopsied, all except one successfully. Three abscesses were aspirated, two intraventricular shunt catheters were sited and in one patient the diagnosis of postradiation gliosis was confirmed and tumour excluded. The advantages and limitations of the technique are discussed. It is advocated as a simple and time-saving alternative to CT stereotactic biopsy in many cases. PMID- 1884596 TI - On the semantic content of subcategorization frames. AB - This paper investigates relations between the meanings of verbs and the syntactic structures in which they appear. This investigation is motivated by the enigmas as to how children discover verb meanings. Well-known problems with unconstrained induction of word meanings from observation of world circumstances suggest that additional constraints or sources of information are required. If there exist strong and reliable parallels between the structural and semantic properties of verbs, then an additional source of information about verb meanings is reliably present in each verb's linguistic context. Five experiments are presented which investigate the following hypothesis regarding the scope of these relations: The closer any two verbs in their semantic structure, the greater the overlap should be in their licensed syntactic structures. To investigate this hypothesis, data of two kinds were collected from different groups of subjects: (a) One group of subjects was asked to judge the semantic relatedness of verbs by selecting the semantic outlier in triads presented to them. (b) A second group of subjects was asked to judge the grammaticality of these same verbs in a large range of syntactic environments. These two types of data were then compared to assess the degree of correspondence in the two partitionings (syntactic and semantic) of the verb set. The findings, overall, support the view that the syntax of verbs is a quite regular, although complex, projection from their semantics. In conclusion, we discuss the kinds of features that are formally marked in syntactic structure and relate these to the problem of verb-vocabulary acquisition in young children. PMID- 1884597 TI - Priming contour-deleted images: evidence for intermediate representations in visual object recognition. AB - The speed and accuracy of perceptual recognition of a briefly presented picture of an object is facilitated by its prior presentation. Picture priming tasks were used to assess whether the facilitation is a function of the repetition of: (a) the object's image features (viz., vertices and edges), (b) the object model (e.g., that it is a grand piano), or (c) a representation intermediate between (a) and (b) consisting of convex or singly concave components of the object, roughly corresponding to the object's parts. Subjects viewed pictures with half their contour removed by deleting either (a) every other image feature from each part, or (b) half the components. On a second (primed) block of trials, subjects saw: (a) the identical image that they viewed on the first block, (b) the complement which had the missing contours, or (c) a same name-different exemplar of the object class (e.g., a grand piano when an upright piano had been shown on the first block). With deletion of features, speed and accuracy of naming identical and complementary images were equivalent, indicating that none of the priming could be attributed to the features actually present in the image. Performance with both types of image enjoyed an advantage over that with the different exemplars, establishing that the priming was visual rather than verbal or conceptual. With deletion of the components, performance with identical images was much better than that with their complements. The latter were equivalent to the different exemplars, indicating that all the visual priming of an image of an object is through the activation of a representation of its components in specified relations. In terms of a recent neural net implementation of object recognition (Hummel & Biederman, in press), the results suggest that the locus of object priming may be at changes in the weight matrix for a geon assembly layer, where units have self-organized to represent combinations of convex or singly concave components (or geons) and their attributes (e.g., aspect ratio, orientation, and relations with other geons such as TOP-OF). The results of these experiments provide evidence for the psychological reality of intermediate representations in real-time visual object recognition. PMID- 1884598 TI - Information integration across saccadic eye movements. AB - The visual world contains more information than can be perceived in a single glance. Consequently, one's perceptual representation of the environment is built up via the integration of information across saccadic eye movements. The properties of transsaccadic integration were investigated in six experiments. Subjects viewed a random-dot pattern in one fixation, then judged whether a second dot pattern viewed in a subsequent fixation was identical to or different from the first. Interpattern interval, pattern complexity, and pattern displacement were varied in order to determined the duration, capacity, and representational format of transsaccadic memory. The experimental results indicated that transsaccadic memory is an undetailed, limited-capacity, long lasting memory that is not strictly tied to absolute spatial position. In all these respects it is similar to, and perhaps identical with, visual short-term memory. The implication of these results for theories of perceptual stability across saccades are discussed. PMID- 1884599 TI - A cluster analysis of manic states. AB - A cluster analysis was performed on 81 manically disturbed patients assessed at interview on items of manic symptomatology and general psychopathology. Four groups were obtained: (1) a mildly excited group, (2) a group characterized by elation and speech disturbance, (3) a small severely disturbed excited group, more schizophrenic than manic, and (4) a group characterized by aggressive overactivity. PMID- 1884600 TI - Further contribution to the conceptual validity of the unified biosocial model of personality: US and Yugoslav data. AB - In this study, the conceptual validity of the unified model of personality, postulated by Cloninger (1987) and measured by the Tridimensional Personality Questionnaire (TPQ), is tested in diverse Yugoslav and American societies. The issue of cross-cultural sensitivity of personality studies and the methodology that minimizes distortions and alternative explanations are discussed in detail. Similar personality structures were observed in the Yugoslav and US samples. Differences in novelty seeking (NS, attributed to age differences between the two samples) and harm avoidance (HA, possibly due to long-standing socioeconomic instability in Yugoslavia) are consistent with the unified biosocial theory of personality. Also, the TPQ was found to be psychometrically sound and valid for further research, although some revision in the reward dependence (RD) scale is warranted. PMID- 1884601 TI - Anxiety in depressive disorders. AB - In this psychopathological study, the subjective experience of anxiety was investigated in depressive patients by means of a semistructured interview. Both International Classification of Diseases-9 (ICD-9) diagnostic criteria (melancholia or neurotic depression; N = 160 or 93, respectively) and the DSM-III classification system (major depressive episode with or without "melancholia"; N = 63 or 153, respectively) were applied. Anxiety can be identified in virtually all patients examined. In contrast, the themes of anxiety are subject to substantial differences. There is a statistically significant correlation between the extent of anxiety and the severity of depression by the Hamilton Depression Scale (Ham-D). However, a distinction between anxiety and depression is possible in the majority of cases if the contents of anxiety are taken into account. PMID- 1884602 TI - Abnormalities in hair trace elements as indicators of aberrant behavior. AB - There are long-standing viewpoints that impulsive and violent behavior may stem from brain dysfunction or damage secondary to head injury, disease, or toxic chemical substances. This research has aimed to examine the relationship between potentially toxic metals and aberrant behavior, especially violent activity, through the nonintrusive technique of hair analysis for trace elements. In an initial study, phase I, it was not possible to replicate findings of others who reported high levels of lead, cadmium, and copper in violent offenders. However, high levels of manganese were found in prison versus control groups. In phase II, the possibility of artifactual results arising from prison cooking utensils was controlled for by sampling early after incarceration. Phase III was included to substantiate the initial post hoc findings in an additional jail population. In both latter phases, significantly elevated manganese levels were found in the hair of violent versus nonviolent subjects (P less than .0001). A review of the effects of manganese at deficient and toxic levels does not provide a simple answer as to why manganese levels are elevated in the hair of individuals who have been incarcerated for violent behavior. Our study does not implicate the prison environment or soaps and shampoos used in California prisons. Other factors, such as alcohol, dietary, or psychosocial factors, might influence manganese levels in hair, or any of these factors might function in combination with mild manganese toxicity to contribute to aberrant behavior. PMID- 1884603 TI - Psychiatric hospitalization of tourists in Jerusalem. AB - Every year some 50 tourists visiting Jerusalem are hospitalized following psychotic episodes. The majority of these patients are from religious backgrounds, and Jerusalem's special place in the Jewish and Christian religions appears to influence the nature of the delusionary experiences. This report examines the factors involved in this phenomenon. PMID- 1884604 TI - Lifetime prevalence of psychiatric disorders in patients with alopecia areata. AB - Thirty-one patients with alopecia areata were administered a structured psychiatric interview (the Diagnostic Interview Schedule; DIS). Overall, 74% had one or more lifetime psychiatric diagnoses. Particularly noteworthy were the high lifetime prevalence rates of major depression (39%) and generalized anxiety disorder (39%). In addition, patients reported increased rates of psychiatric disorders in first-degree relatives: anxiety disorders (58%), affective disorders (35%), and substance use disorders (35%). Patients with patchy alopecia areata were more likely to have a diagnosis of generalized anxiety disorder. No relationships were found between major depression and any variable characterizing alopecia areata history. Possible interrelationships between psychiatric disorders and alopecia areata are discussed. The study suggests that patients with alopecia areata are at increased risk for psychiatric disorders, and calls attention to the need for psychiatric assessment in this population. PMID- 1884605 TI - Concordance between two personality disorder instruments with psychiatric inpatients. AB - Eighty-two psychiatric inpatients received axis II diagnoses on the Millon Clinical Multiaxial Inventory (MCMI-1)--a self-report instrument--and the Structured Interview for DSM-III Personality (SIDP). Those two instruments were then compared in terms of personality disorder categories and trait-scores (dimensions). Essentially, with the exception of the borderline category, concordance between the two instruments was poor on all scales. Bayesian statistics confirmed the obtained results. The adequacy of the MCMI-I as an index of DSM-III personality disorders is questioned. PMID- 1884606 TI - Predictors of serious suicide attempts among patients with panic disorder. AB - Of 74 panic disorder subjects followed up after 7 years, five reported serious suicide attempts and three had completed suicide. Compared with subjects who had not made serious attempts, the serious suicide attempters (including the three suicides) were younger, and fewer of them were married. Also, the serious attempt group had an earlier, more gradual onset of illness. More of the serious attempters had personality disorders and coexisting major depression. At the time of original assessment, the serious attempters had more severe symptoms. These data suggest that among patients with panic disorder, serious suicidal behavior is associated with more severe psychopathology. PMID- 1884607 TI - Drug and alcohol dependence and psychiatric populations: the need for diagnosis, intervention, and training. AB - The comorbidity of psychiatric disorders and alcohol and drug dependence is high. The prevalence rate for each disorder is high as determined by studies in general and patient populations. Moreover, the severity of the course is likely to be greater when the two disorders are combined, prompting the attention of clinicians and researchers. Of importance, the intoxication and withdrawal from alcohol and drugs produce psychiatric symptoms and syndromes that can mimic psychiatric disorders. The prevalence rates for comorbidity of both categories of disorders vary according to the populations studied, methodological approaches used, and duration of longitudinal follow-up postdiagnosis of the disorders. It is evident from a review of the literature that there is a growing urgency for proper diagnosis, improved training programs, and treatment intervention strategies for alcohol and drug dependence in psychiatric populations. Suggestions for broad assessment and specific interventions for alcohol/drug dependence in psychiatric settings are offered, and increased time in psychiatric residency training is recommended. PMID- 1884608 TI - Critical care publishing: rules of the game. PMID- 1884609 TI - Treatment of gram-negative septic shock with an immunoglobulin preparation: a prospective, randomized clinical trial. AB - OBJECTIVE: To evaluate the effectiveness of a polyclonal immunoglobulin (Ig) preparation containing IgG, IgM, and IgA as an adjunctive therapy for septic shock. DESIGN: Prospective, randomized clinical trial. SETTING: A clinical immunology ward at the center for internal medicine in a university hospital. PATIENTS: Fifty-five patients with septic shock were randomly allocated to two groups according to criteria of septic shock. INTERVENTION: One group of patients (n = 27) received a commercially available immunoglobulin preparation (containing high titers of antibodies specific for determinants to bacterial endotoxin) during the first 3 days after inclusion in the study. The other randomized group (n = 28) did not receive any immunoglobulin preparation. MEASUREMENTS AND MAIN RESULTS: During the period of less than or equal to 6 wks after the beginning of clinically apparent septic shock, death related to the septic process occurred in one (4%) of 27 patients who received immunoglobulin. By comparison, nine (32%) of 28 control group patients died during this period (p less than .01). Within the first 48 hrs after onset of the clinically apparent septic process, significantly increased activity of circulating endotoxin and simultaneously decreased specific IgG serum titers to lipid A were detected in the group of nonsurvivors. CONCLUSION: Administration of a polyclonal immunoglobulin preparation in the early phase of septic shock was associated with significantly improved survival. PMID- 1884610 TI - Differential detection of plasma hydroperoxides in sepsis. AB - OBJECTIVE: To determine whether plasma lipid hydroperoxides may be a useful marker for sepsis. DESIGN: Exploratory, open-label study. SETTING: Critical care unit at a university medical center. PATIENTS: Twelve patients with sepsis syndrome requiring hemodynamic monitoring with pulmonary artery catheters. Seven patients were diagnosed with pulmonary infections and five patients had intra abdominal infections. INTERVENTIONS: Fatty acid hydroperoxide was measured in the fresh arterial plasma (radial artery) and mixed venous plasma (pulmonary artery) from each patient. Hydroperoxide was determined using a sensitive assay based on activating the cyclooxygenase reaction of prostaglandin H synthase. MEASUREMENTS AND MAIN RESULTS: The mean difference between the amount of fatty acid hydroperoxide measured in the plasma draining involved regions (arterial plasma for pulmonary sepsis, mixed venous plasma for intra-abdominal sepsis) compared with the paired, uninvolved regions was 0.45 +/- 0.14 microM (mean +/- SEM; p less than .005). CONCLUSIONS: Increased lipid hydroperoxides in blood-draining septic foci are markers of oxyradical release associated with severe infection, although they are not specific for infectious conditions, being released also from nonseptic regions of surgical trauma. Assays for hydroperoxides may be useful when relatively free of other tissue trauma. PMID- 1884611 TI - Lactic acid kinetics in respiratory alkalosis. AB - OBJECTIVE: To evaluate the impact of respiratory alkalosis on the elimination of intravenously infused lactate. DESIGN: Prospective, randomized, crossover study. SETTING: Medical ICU of a university hospital. PATIENTS: Eight patients treated by ventilatory support for neurologic or neuromuscular diseases. INTERVENTIONS: Patients were investigated on two occasions: during normoventilation (pH 7.42 +/- 0.1, PCO2 41 +/- 2 torr [5.5 +/- 0.2 kPa]) and during respiratory alkalosis (pH 7.59 +/- 0.1, PCO2 27 +/- 2 torr [3.6 +/- 0.2 kPa]) induced by controlled hyperventilation. To evaluate lactate elimination kinetics, 1 mmol/kg body weight of L-lactic acid was infused over 5 mins. MEASUREMENTS AND MAIN RESULTS: Arterial lactate concentrations and blood gas values were determined before and repeatedly after the infusion. Lactate elimination variables were calculated from the plasma curve by using a two-compartment model. Respiratory alkalosis increased plasma lactate from 1.56 +/- 0.1 to 2.49 +/- 0.2 mmol/L (p less than .001). The lactate elimination half-life increased from 4.57 +/- 0.2 mins at pH 7.42, to 9.96 +/- 1.1 mins during pH 7.59 (p less than .01), and beta half-life increased from 12.2 +/- 1.9 to 44.1 +/- 1 mins (p less than .01). Whole-body clearance decreased 40% from 24.2 +/- 2.9 to 14.3 +/- 2.0 mL/kg body weight-min (p less than .01). CONCLUSIONS: Respiratory alkalosis increases the basal concentration of plasma lactate and decreases clearance of infused lactic acid. These findings provide further evidence of the adverse effects of alkalosis. PMID- 1884612 TI - Noninvasive optimization of left ventricular filling using esophageal Doppler. AB - OBJECTIVE: To confirm whether the descending aortic blood flow velocity waveform variable of flow time corrected for heart rate, measured using an esophageal Doppler transducer, can be used for noninvasive optimization of left ventricular (LV) filling. SETTING: ICU and operating theater. SUBJECTS: Forty-three mechanistically ventilated patients in the ICU or undergoing cardiothoracic surgery in whom a pulmonary arterial catheter was in situ. INTERVENTIONS: LV preload was a) increased from hypovolemic states (pulmonary arterial occlusion pressure [PAOP] less than 8 mm Hg) by fluid challenge, b) decreased from normovolemic states (PAOP 10 to 15 mm Hg) by either iv nitrates or intravascular fluid loss, and c) decreased from heart failure or fluid overload states (PAOP greater than 20 mm Hg) by iv nitrates. No other maneuver was performed concurrently. MEASUREMENTS AND MAIN RESULTS: Descending aortic blood flow was measured by an esophageal Doppler transducer. Corrected flow time was calculated by dividing systolic flow time by the square root of the cycle time. PAOP and corrected flow time increased after fluid challenges in hypovolemic states, and decreased when LV preload was decreased from normovolemic states. However, when preload was decreased from overload states, PAOP always decreased, but the corrected flow time usually increased before any subsequent decrease. The greatest value of corrected flow time corresponded with the maximal stroke volume seen. CONCLUSIONS: Esophageal Doppler measurement of aortic blood flow can be used for rapid, noninvasive optimization of LV filling in mechanically ventilated patients. PMID- 1884613 TI - Septic shock and multiple organ failure. AB - OBJECTIVE: To assess the frequency and mortality rates of septic shock in ICU patients and the clinical course of multiple organ failure associated with septic shock. DESIGN: Retrospective case survey. SETTING: Tertiary care center. PATIENTS: During a 2-yr period, 2,469 consecutive intensive care patients were studied regarding the frequency and hospital mortality rates of septic shock. A subset of 1,311 patients was further analyzed for the occurrence of organ system failures within 48 hrs of the onset of septic shock and again 4 to 7 days later. MEASUREMENTS AND MAIN RESULTS: The frequency rate of septic shock was 1.9% (n = 48), with a mortality rate of 72.9% (n = 35) in patients with septic shock. Deaths due to septic shock represented 14.6% of all deaths in the ICU during the study period. Eighteen patients died within 72 hrs of the onset of septic shock. Refractory hypotension was the cause of death in 15 of these 18 patients. Beyond 72 hrs, multiple organ failure accounted for eight of 17 deaths. The mean +/- SD number of organ systems failing at 48 hrs was 3.3 +/- 1.3 in survivors and 4.0 +/ 1.1 in nonsurvivors, and at 4 to 7 days was 2.1 +/- 1.5 in survivors and 4.0 +/- 1.5 in nonsurvivors (p less than .05). None of the specific organ system failures had prognostic value. The number of organ system failures was not related to the duration of hypotension, but had a weak correlation (r2 = .26, p less than .05) with the duration of vasoactive treatment at 4 to 7 days. The prolonged need for norepinephrine therapy was associated with an increased occurrence of renal failure. Thirty (62.5%) patients had positive blood cultures and a mortality rate similar to the mortality rate of patients with negative blood cultures. Patients with negative blood cultures died more often with hypotension (p less than .02). CONCLUSIONS: Septic shock is a major cause of death in intensive care patients. Refractory hypotension is a main cause of early deaths. Later on, multiple organ failure becomes the primary clinical problem and cause of mortality. PMID- 1884614 TI - Respiratory complications in critically ill medical patients with acute upper gastrointestinal bleeding. AB - STUDY OBJECTIVE: To determine types of respiratory complications encountered in critically ill patients with serious acute upper gastrointestinal (GI) bleeding, and to identify associated risk factors. DESIGN: Retrospective chart review. SETTING: A university hospital medical ICU. PATIENTS AND METHODS: We reviewed medical records of 86 patients admitted to the medical ICU over a 2 1/2-yr period of time, for 107 consecutive episodes of serious acute upper GI bleeding. Clinical features of patients who developed respiratory complications of pneumonia, witnessed aspiration of gastric contents, or who required intubation and mechanical ventilation for other reasons were compared with those features of patients without respiratory complications. MAIN RESULTS: Respiratory complications occurred during 23 (22%) serious upper GI bleeding episodes (mean transfusion requirement, 7 units of packed RBCs). Twelve patients developed pneumonia and all had evidence of advanced liver disease. Five patients were observed to aspirate gastric contents and six patients require intubation and mechanical ventilation for reasons other than pneumonia or aspiration. Esophageal sites of bleeding (esophagitis, esophageal ulcers and esophageal varices), advanced liver disease, age greater than 70 yrs, and an Acute Physiology and Chronic Health Evaluation (APACHE) II score greater than 13 appeared to be risk factors. Mortality rate was increased in patients with respiratory complications: 70% of patients with respiratory complications died, compared with 4% of those patients without such problems (p less than .001). CONCLUSIONS: Respiratory complications are common in critically ill medical patients with serious acute upper GI bleeding, and are associated with a poor outcome. Risk factors include advanced liver disease, esophageal site of bleeding, age greater than 70 yrs, and higher APACHE II score. PMID- 1884615 TI - "Near miss" death in obstructive sleep apnea: a critical care syndrome. AB - OBJECTIVE: The objective of this study was to alert critical care physicians to the syndrome of obstructive sleep apnea with respiratory failure ("near miss" death) and to elucidate characteristics that might allow earlier recognition and treatment of such patients. DESIGN: We examined clinical and laboratory characteristics of eight patients with obstructive sleep apnea presenting to the ICU with respiratory failure. These characteristics were compared with those of eight stable apnea patients of similar severity but without a history of presentation with respiratory failure. SETTING: Medical ICU and pulmonary outpatient clinic at the Houston Veterans Administration Medical Center, a teaching hospital affiliated with Baylor College of Medicine. PATIENTS: Eight patients with obstructive sleep apnea who presented in, or developed, acute respiratory failure requiring tracheal intubation and mechanical ventilation were matched to eight stable obstructive sleep apnea outpatients from the chest clinic. MEASUREMENTS AND MAIN RESULTS: The records of these 16 patients were reviewed and multiple characteristics that might predict these obstructive sleep apnea patients prone to respiratory failure and death (called the "near miss" death group; n = 8) were examined. The mean age of the near miss group was 57 yrs. All eight patients presented with respiratory acidosis (mean pH 7.22), hypercarbia (mean PaCO2 82 torr [10.9 kPa]), and hypoxemia (mean PaO2 45 torr [6.0 kPa]). Six of the eight patients had concomitant chronic obstructive pulmonary disease as determined by clinical characteristics and spirometry. Predisposing factors included facial trauma, lower respiratory tract infections or bronchospasm, and use of pain medication. All but one of the near miss subjects had awake hypercarbia (mean PaCO2 49 torr [6.5 kPa]) and hypoxemia (mean PaO2 58 torr [7.7 kPa]) during periods of clinical stability while only two controls had concomitant chronic obstructive pulmonary disease and none had hypercarbia. The prevalence of a history of wheezing and prior hospitalization for "respiratory problems" were greater in the near miss group. Once cured of apnea, no patient presented with recurrence of respiratory failure in follow-up ranging from 6 to 80 months, and cor pulmonale recurred in only one patient during subsequent onset of central apneas. CONCLUSION: Patients with obstructive sleep apnea who have concomitant chronic obstructive pulmonary disease or hypercarbia and hypoxemia are more prone to develop severe respiratory failure and probable death than those patients with apnea alone. The current study shows that recurrent respiratory failure and presumably mortality from this acute complication can be reversed with effective treatment of the obstructive apnea. PMID- 1884616 TI - Comparison of disease severity scoring systems in septic shock. AB - OBJECTIVE: To compare six disease severity scoring systems as predictors of mortality in septic shock when used in the first 24 hrs of diagnosis. The six scoring systems tested were: Multiorgan Failure; the Acute Organ System Failure; the Acute Physiology and Chronic Health Evaluation (APACHE II); the Multisystem Organ Failure scoring system; the Mortality Prediction Model; and the grading of sepsis. DESIGN: Retrospective, case series, consecutive sample. SETTING: Adult ICUs of three teaching hospitals. PATIENTS: Seventy-one patients from 12 to 84 yrs, fulfilling specific criteria for the diagnosis of septic shock, who were admitted to the ICU during 15 consecutive months. MEASUREMENTS AND MAIN RESULTS: The Multiorgan Failure scoring system, Acute Physiology and Chronic Health Evaluation (APACHE II), and Acute Organ System Failure scoring system were found, with our modifications, to be statistically significant predictors of mortality. Predictive data for these three scoring systems were as follows: Multiorgan Failure scoring system p = .008, mean number of points of survivors 5.2 +/- 1.5 (SD), mean number of points of nonsurvivors 6.3 +/- 1.5; APACHE II p = .013, mean number of points of survivors 21.1 +/- 5.9, mean number of points of nonsurvivors 24.6 +/- 6.0; and Acute Organ System Failure scoring system p = .011. None of the other three scoring systems showed significant predictive ability: Multisystem Organ Failure scoring system p = .072, Mortality Prediction Model p = 0.091, and the grading of sepsis p = .27. There was a significant (p = .004) difference in the survival rate of the three hospitals. CONCLUSION: The Multiorgan Failure scoring system, APACHE II, and the Acute Organ System Failure scoring system, with minor modifications, were found to be useful prognostic tools for patients with septic shock and allowed us to compare the performance and treatment programs of different ICUs. PMID- 1884617 TI - Postsepsis bradycardia in children with leukemia. AB - OBJECTIVE: We observed sinus bradycardia in a small number of children with hematologic malignancies who were recovering from sepsis. Our objective was to define this symptom complex and attempt to delineate its etiology. DESIGN: Retrospective chart review. SETTING: A pediatric ICU in a children's oncology hospital. PATIENTS: Children admitted to the ICU over a 24-month period who developed persistent bradycardia (heart rate less than 5% for age for greater than 1 hr) after an episode of sepsis. MEASUREMENTS AND MAIN RESULTS: Seven children developed postsepsis bradycardia. Six patients had a primary diagnosis of acute myelogenous leukemia and one patient had acute lymphocytic leukemia. All patients had positive blood cultures (Streptococcus mitis, n = 4; Escherichia coli, n = 2; and Klebsiella pneumoniae, n = 1). All seven children were clinically recovering from sepsis when the bradycardia developed. Neither hypotension nor other symptom was associated with the bradycardia. No therapy was given for the bradycardia. Echocardiograms and ECGs were normal in all patients, except for the presence of bradycardia. Bradycardia persisted for 24 to 72 hrs. After that time, heart rates slowly increased to the normal range for age. CONCLUSIONS: We speculate that this syndrome may result from alterations in beta adrenergic receptor function or an unidentified humoral factor produced by the invading organism or as part of the host's response to sepsis. Prior drug therapy or the underlying illness may predispose to this condition, since all the patients had acute leukemia. As the bradycardia was clinically insignificant, invasive therapeutic or diagnostic strategies were not indicated. PMID- 1884618 TI - Liver glutathione and cytochrome P450 activity in experimental infection: study of the relative effects of infectious stress and malnutrition. AB - OBJECTIVE: To study the effects of infection and malnutrition on liver glutathione and cytochrome P450 (P450) in rats. DESIGN: Controlled experimental groups (12 groups). ANIMALS: Adult male Sprague-Dawley rats. INTERVENTIONS: Experimental endocarditis, pyelonephritis, or peritonitis were caused. Controls included free-fed rats and sham-operated rats, pair-fed to infected animals. Infection was verified by tissue culture. Rats were killed 3 days (acute infection) or 10 days (chronic infection, except endocarditis) after the induction of infection. RESULTS: Sham rats had lower liver weights, liver/body weight, and liver glutathione values than controls. Infected rats had larger liver weights and liver/body weight ratios and liver glutathione content than shams, and larger liver/body weight ratios than controls (acute infection). Infected rats had lower P450 values than both shams and controls. CONCLUSION: The malnutrition associated with infection caused decreased liver weight and glutathione content. Infection increased the liver weight, and liver glutathione content, but caused severe reduction in liver P450. If the same finding is true in infected patients, it could have consequences for the management of such patients. PMID- 1884619 TI - Cardiac function after hepatic ischemia-anoxia and reperfusion injury: a new experimental model. AB - BACKGROUND AND METHODS: During liver transplantation, reperfusion of the donor liver and in the clinical setting, end-stage liver disease, have occasionally resulted in profound cardiovascular disturbances. The etiology of hepatic injury induced myocardial dysfunction is still unclear. In this study, the aims were to develop an experimental model that would facilitate the study of the effects of hepatic failure on myocardial function and to determine whether hepatic ischemia or anoxia and reperfusion injury of similar duration would result in the same degree of hepatic failure. Seventy male Sprague-Dawley rats were used as organ donors. Three simultaneous liver-heart perfusions (corresponding to three groups) were established using a modified Krebs-Henseleit buffer with 2% bovine albumin, membrane oxygenation, and a peristaltic pump. Group 1 (n = 10) and group 2 (n = 15) experiments consisted of liver-heart perfusions after 90 mins of normothermic hepatic ischemia or 90 mins of hepatic anoxia, respectively, followed by reoxygenation and 60 mins of reperfusion. Group 3 (n = 8) experiments consisted of sham liver-heart perfusions studied over the same experimental time period (60 mins). Myocardial function variables, liver function tests, arterial blood gases, and electrolytes were measured at baseline and at 3-, 10-, 30-, and 60-min intervals during reperfusion in all experiments. RESULTS: Ischemia or anoxia induced hepatic failure resulted in a similar degree of hepatic dysfunction. Both forms of acute hepatic failure caused significant increases in liver function tests, a reduction in heart rate (p less than .05), coronary flow (p less than .05), and an increase in calculated coronary vascular resistance (p less than .05). There were no changes in buffer pH, CO2, or ionized calcium that could explain the coronary vasoconstriction. CONCLUSIONS: Hepatic dysfunction induced by ischemia or anoxia of similar duration results in a similar hepatic metabolic profile during reperfusion and can cause direct myocardial dysfunction of the isolated perfused rat heart. PMID- 1884621 TI - Fellowship programs in critical care medicine: 1991/1992. The Society of Critical Care Medicine. PMID- 1884620 TI - Heparin treatment in thrombin-induced disseminated intravascular coagulation in the baboon. AB - BACKGROUND AND METHODS: We postulated that low-dose heparin (10 IU/kg.hr) administered as a continuous iv infusion may prevent or ameliorate the induction of thrombin-induced disseminated intravascular coagulation in baboons under general anesthesia. In a nonrandomized experiment lasting 8 hrs, animals were divided into three groups: 11 received thrombin only (group A); ten were pretreated with heparin before thrombin administration (group B); and 15 received heparin 2 hrs after disseminated intravascular coagulation was induced with thrombin (group C). All animals were monitored hemodynamically and coagulation tests were performed hourly. Tests included the following: one-stage prothrombin ratio; activated partial thromboplastin time; fibrinogen and fibrin degradation products; thrombin time; plasma fibrinogen level; antithrombin III and activated clotting time. After the acute phase of the experiment, the animals were observed for 6 days and a postmortem examination was performed on a survivor of each group. RESULTS: Six (55%) group A animals died within 6 days, while there were no deaths in group B and one animal (7%) died in group C. In group C, the administration of heparin could not normalize the clotting profile, but the mortality rate was significantly less than in group A. The prophylactic administration of heparin in group B prevented the induction of disseminated intravascular coagulation. The postmortem findings were of interest, but no statistically valid conclusions could be made, as only one autopsy was done for each group. However, the results suggest that heparin pretreatment may protect against lung edema and liver necrosis. CONCLUSIONS: The results suggest that heparin, in a dose of 10 IU/kg.hr iv, could possibly be safely used in patients at high risk of developing disseminated intravascular coagulation and in those patients with established disseminated intravascular coagulation. PMID- 1884622 TI - Recurrent pulmonary arterial hypertension following neonatal treatment with extracorporeal membrane oxygenation. PMID- 1884623 TI - Transesophageal echocardiography for assessing the cause of hypotension. PMID- 1884624 TI - Postganglionic Horner's syndrome after insertion of a pulmonary artery catheter through the internal jugular vein. PMID- 1884625 TI - Mild hypothermic cardiopulmonary resuscitation. PMID- 1884626 TI - Acute edema after administration of 50% dextrose solution. PMID- 1884627 TI - Percutaneous dilational tracheostomy. PMID- 1884628 TI - Clinical management of intersex abnormalities. PMID- 1884629 TI - Vibrio virulence factors and the quantitative analysis of cytotoxicity elaborated by environmental isolates. AB - Vibrio strains isolated from freshwater environments were screened for the elaboration of haemolysin, cytotoxin and enterotoxins. While characterizing for various toxins, nine strains elaborated 10(3) and more haemolytic units (HU) per ml crude toxin with a maximum of 4.1 x 10(3) HU. About 41.7% of the strains which were tested produced a factor in the culture supernatant which was active in the suckling mouse assay. Cytotoxin studies revealed that all the Vibrio strains did not respond uniformly in the three cell lines tested. The elongation factor of the CHO cell line which was reported to have correlation with the enterotoxic activity, did not with some exceptions correspond to high fluid accumulation ratio in conventional suckling mouse assay. A modified, simple, rapid, sensitive procedure is described to quantify the elaboration of cytotoxic units (CU). When the HeLa cell line was used to estimate the CU production, 29% of the strains produced 10(2) CU with a maximum of 169 CU per 50 microliters of crude toxin. PMID- 1884630 TI - Influence of insulin and biogenic amines on the division of Chang liver cells after primary exposure (imprinting) and repeated treatments. AB - Cells of the Chang liver line responded differently to insulin and histamine exposure and re-exposure after five pretreatments. The mitotic index showed a considerable relative decrease 72 h after the last pretreatment. The response to serotonin did not differ between pretreatment and re-exposure. The effect of insulin and of biogenic amines was positive at the primary exposure and negative 72 h after repeated pretreatments. PMID- 1884631 TI - Morphogenesis of the flagellum in the spermatids of Coelomera lanio (Coleoptera, Chrysomelidae): ultrastructural and cytochemical studies. AB - The flagellum of Coelomera lanio has a single axoneme with a 9 + 9 + 2 axoneme pattern and the microtubules are linked to the E-PTA positive dinein arms. The electron-dense fibres between microtubules show a positive acid phosphatase reaction. A single E-PTA positive accessory body is seen flanking the axoneme, from which extends a puff-like corpuscle. On the opposite side of the accessory body, away from the axoneme, exists another puff-like corpuscle. The mitochondrial complex gives rise to two mitochondrial derivatives of different shapes and sizes. The major derivative possesses a paracrystalline corpuscle and the minor has an electron-dense area in the juxta-axonemal region. All these structures are involved in the mechanism of flagellar motility. PMID- 1884632 TI - The role of the surface energy of water in the conformational changes of the human erythrocyte glucose transporter. AB - There is now strong experimental evidence that the red cell glucose transporter protein operates by a conformational change which has the effect of presenting a sugar binding site to the outside and inside medium of the cells in an alternating manner, but the way in which this is brought about is still unknown. Kinetic evidence that the conformational changes which create the inward and outward facing modes can occur in the absence of a sugar substrate has been put on a firmer experimental basis by Appleman and Lienhard (1989). Conformational changes of the magnitude envisaged are too large to be attributed only to spontaneous thermal agitation in the protein. Theoretical considerations show that the surface energy of water could be an alternative source of energy which, in a suitable reciprocating cycle of activity, could sustain the conformational changes throughout the existence of the transporter. PMID- 1884633 TI - Long-term postoperative dysphagia in oral/pharyngeal surgery patients: subjects' perceptions vs. videofluoroscopic observations. AB - Dysphagia commonly results from surgical resection of various structures within the oral, pharyngeal, and esophageal areas. The type and severity of swallowing dysfunction are based largely on the number and quantity of structures removed as well as the reconstructive procedure. Short term-recovery has been addressed in many studies. However, follow-up studies of long-term functional results and continuing swallowing problems following oral/pharyngeal surgery are unavailable. In this study, perception of swallowing dysfunction was compared with actual videofluoroscopic findings in subjects at least 1 year after oral/pharyngeal surgery. The comparative results of a questionnaire developed to evaluate patients' perception of continuing swallowing difficulty and an analysis of actual videofluoroscopic tapes indicated that the degree or type of dysphagia could not be determined from patients' subjective descriptions of the swallowing problem. PMID- 1884634 TI - Circumoral movements in response to three different food textures in children 6 months to 2 years of age. AB - The purpose of this study was to establish an objective description of circumoral behavior in normal children during the oral phase of ingestion. The response to three different food textures--solid, viscous, and puree--was examined in 143 healthy children aged 6 months to 2 years. Feeding sessions were videotaped and data analyzed using criteria for describing circumoral structures during anticipation of food, removal of food from a spoon, as well as the initiation of chewing and swallowing. As children get older their feeding behaviors mature, which is characterized by better lip control, increased mobility of the tongue, and decreased involvement of the circumoral structures in swallowing. These data are intended for clinicians who evaluate young children with feeding impairments in order to determine children's functional age level. PMID- 1884635 TI - Dysphagia in psychiatric patients: clinical and videofluoroscopic study. AB - Deaths due to airway obstruction are more common in psychiatric inpatients than in the normal population. A dysphagia program was started in a 400 bed Massachusetts psychiatric hospital after 4 patients in 1 year died from asphyxia. In the year after the program was started, there were no deaths; however, 28 patients experienced 32 choking incidents. The 28 patients received clinical evaluations by speech pathologists, neurologists, psychiatrists, and internists. Of the incidents, 55% required use of the Heimlich maneuver to open the airway. Choking incidents could be classified into five types based on results of clinical examination: bradykinetic, dyskinetic, fast eating syndrome, paralytic, and medical. Twenty-one of the 28 patients were studied by videofluoroscopy and 86% of the videos were abnormal, showing aspiration in eight, webs in five, and delay in the oral phase in five. Patients with bradykinetic dysphagia (secondary to neuroleptic-induced extra-pyramidal syndrome [EPS]) and paralytic dysphagia appeared to experience a more severe form of choking. PMID- 1884636 TI - Image processing in swallowing and speech research. AB - An image processing system for application to studies of the temporal and spatial parameters of movement during swallowing and speech is described. Image sequences from videotape are digitized for computerized manipulation and analysis in an attempt to improve on conventional visual inspection. The system is "interactive" or "event-driven": after executing a function, the computer waits for guidance from the user who controls the program through keyboard and mouse input, selecting options from menus and responding to prompts. The analyst alters image clarity by the application of filters and heightens contrast through video enhancement. A technique called "remapping" reduces head motion and provides uniform spatial scaling. Animated sequences of images are used, as opposed to frame-by-frame analysis, to preserve temporal context and increase efficiency of measurement. Low cost off-the-shelf personal computer hardware is used along with original software tailored to the application. PMID- 1884638 TI - Radiology corner. Neuromuscular disorder. PMID- 1884637 TI - Nonsurgical treatment of drooling in a patient with closed head injury and severe dysarthria. AB - The purpose of this investigation was to measure the effectiveness of the antimuscarinic drug atropine sulfate in the treatment of chronic drooling in a patient with a history of severe closed head injury and resultant widespread oral neuromuscular and higher cortical disturbances. Results of the A-B-A-B-A-B withdrawal paradigm, chosen to demonstrate the functional relationship between drug therapy and the degree of drooling, revealed that administration of atropine sulfate reduced by more than 50% of baseline levels the amount of resting secretion, intraoral accumulation, and pharyngeal-laryngeal pooling of saliva, with negligible side effects. These results are discussed and compared to the alternative drug and surgical approaches to treatment that have been the primary focus of recent research on drooling. PMID- 1884639 TI - Dysphagia after Nissen fundoplication. AB - Nissen fundoplication is a commonly used antireflux operation. After this operation symptoms such as dysphagia, inability to belch and vomit, and gas bloating are frequently reported in the literature. In 32 patients who underwent Nissen fundoplication 3.5-18 years ago, postprocedure dysphagia was studied using conventional manometry and 24 h ambulatory pressure and pH recording. Our study indicates that dysphagia tends to decrease after surgery. Neither conventional nor ambulatory pressure recording revealed motor abnormalities that could be held responsible for the dysphagia. Therefore, the data do not support the concept that dysphagia is a major complication of Nissen fundoplication. PMID- 1884640 TI - Abnormalities of vascular reactivity in the sepsis syndrome. PMID- 1884641 TI - Shock- and ischemia-induced mechanisms of impairment of endothelium-mediated vasodilation. PMID- 1884642 TI - Role of endotoxin and host cytokines in septic shock. PMID- 1884643 TI - Macrophages in acute and chronic inflammation. PMID- 1884644 TI - Role of uric acid as an endogenous radical scavenger and antioxidant. PMID- 1884645 TI - Therapeutic application of oxygen radical scavengers. PMID- 1884646 TI - Acute disturbances of renal function. PMID- 1884647 TI - Prevention and treatment of secondary brain damage. Clinical aspects. PMID- 1884648 TI - Multisystem organ failure in neurosurgical patients. PMID- 1884649 TI - The brain in shock. Secondary disturbances of cerebral function. PMID- 1884650 TI - Once-daily ceftriaxone in the treatment of lower respiratory tract infections. AB - We conducted a retrospective clinical evaluation to assess the efficacy of a 1 gram once-daily regimen of intravenously administered ceftriaxone in the treatment of a variety of bacterial infections. Of the 250 patients studied, 167 had infections of the lower respiratory tract, approximately 70% of which were diagnosed as community-acquired pneumonias. The principal identified pathogens were Staphylococcus aureus and Haemophilus influenzae. Forty per cent of community-acquired pneumonias occurred in patients over 69 years of age, who showed a 13% mortality compared to a mortality rate of 4% in younger patients. Once-daily ceftriaxone was effective and well tolerated as empiric therapy for pneumonia likely to be caused by susceptible organisms. PMID- 1884651 TI - Once-daily ceftriaxone in the outpatient treatment of paediatric infections. AB - Parenteral ceftriaxone was administered as a once-daily outpatient treatment to a selected low-risk population of neonates, infants, and children with moderate to severe bacterial infections. No incidences of treatment failure were seen in 200 children with uncomplicated infections responsive to ceftriaxone therapy. The mean period of outpatient treatment in initially hospitalized children with non CNS infections, excluding endocarditis, was 1-3 days. Ceftriaxone outpatient management was successful in the control of organisms causing meningitis (n = 54), periorbital facial cellulitis (n = 16), sinusitis (n = 10), arthritis (n = 6), endocarditis (n = 4), and other infections. PMID- 1884652 TI - [The millisecond pulsed Y.A.G. laser and the microsecond pulsed Y.A.G. laser in the treatment of dental caries]. PMID- 1884653 TI - [Supernumerary teeth and their consequences. Therapeutic approach]. PMID- 1884654 TI - The pulmonary artery catheter. AB - First developed more than 20 years ago as a research tool for investigations of myocardial infarction, the pulmonary artery or Swan-Ganz catheter has gained general usage as a valuable clinical tool. Its development paralleled the rapid growth of technological advancements in clinical medicine. Rapid incorporation of technological advancements into clinical practice, however, is not without risk. Care must be taken to assure that clinicians possess the understanding of both basic concepts and requisite hardware to provide quality patient care. Equipment selection and calibration, patient selection, data interpretation, potential complications, troubleshooting, and procedure limitations must all be considered. Broader application of the Swan-Ganz catheter in surgery, anesthesiology, and critical care as well as in cardiology has provided information on hemodynamics that has had considerable impact on diagnostics as well as on therapy for patients with a wide variety of clinical conditions. PMID- 1884655 TI - [The coincidence of energy and morphological dynamics in hepatocytes in culture]. PMID- 1884656 TI - [Serotonin diminishment of radiation damage in mouse embryogenesis]. PMID- 1884657 TI - [The identification of chromosome aberrations reflecting genome instability in the progeny of irradiated cells]. PMID- 1884658 TI - [The identification of the functional alpha-glucosidase gene in natural mutants of Saccharomyces cerevisiae and S. paradoxus that do not ferment maltose]. PMID- 1884659 TI - [An electron microscopic study of the regeneration process in minced muscle tissue in newborn rat pups]. PMID- 1884660 TI - [A new serologically undetectable subtype of the HLA-B27 gene--the result of reciprocal interallelic recombination and point mutations: the data from a comparative structural analysis]. PMID- 1884661 TI - [Amphiphilic aliphatic acids--activators of 5-lipoxygenase. The adsorption micellar regulatory mechanism]. PMID- 1884662 TI - Chlormethiazole: current status in the treatment of the acute ethanol withdrawal syndrome. AB - Comparative clinical studies of Chlormethiazole with a vast array of pharmacologically unrelated drugs like benzodiazepines, tiapride, bromocriptine, carbamazepine and phenothiazines over the years clearly established it as a useful, dependable and effective drug to treat patients with moderate to severe ethanol withdrawal syndrome, when used early in a flexible reducing regime tailed off over 7-10 days. It has been found to be highly effective in the treatment, and particularly in the prevention of DT's in high-risk patients, if given at an early stage. This paper critically reviews the important international clinical trial literature of various drugs currently used in the treatment of ethanol withdrawal syndrome, including DT's, it highlights the efficacy and superiority of Chlormethiazole over other drugs, and also discusses the probable mechanism of its actions in these conditions. PMID- 1884663 TI - Drug dependence and personality disorder: its relationship to the treatment of drug dependence. AB - A perennial debate regarding drug dependence is the issue of the contribution of psychopathic personality disorder to dependence behaviour. The research reported here suggests that the effects of treatment appear to have little effect on underlying psychopathy. However, levels of psychopathy seem irrelevant to treatment outcome. PMID- 1884664 TI - Starting, switching, stopping: users' explanations of illicit drug use. AB - Seventy-two regular illicit drug users were interviewed at two time points (December 1987 to June 1988 and September 1989 to April 1990) as part of a longitudinal study which aims to assess changing patterns of drug use in the community. Descriptive information relating to initiation, continuation and cessation is presented using quotations from drug users made to the author during extensive periods of fieldwork. The existence of a myriad of personal, social and economic factors which combine to facilitate and maintain drug involvement is apparent. The implications with regard to education and prevention are discussed. PMID- 1884665 TI - The reliability and stability of a quantity-frequency method and a diary method of measuring alcohol consumption. AB - The study aimed to assess the test-retest reliability of two commonly used measures of alcohol consumption, the quantity-frequency (QF) method and the diary method, as well as the stability of scores on the two measures over time. Two methods of assessing reliability and stability were employed. The first was a traditional method based on calculation of correlation coefficients for agreement between scores on repeated measures over a short retest interval to yield test retest reliability coefficients, and over a long retest interval to yield stability coefficients. The second method was that devised by Wiley and Wiley (1970) to differentiate the effects of reliability and stability on repeated measures over time. The two methods were applied to a sample of heavy drinkers and to a sample of light drinkers. The results indicated that both the QF and diary measures are reliable in measuring alcohol consumption of light drinkers. Both measures are less reliable for heavy drinkers. The results indicate, in addition, that drinking consumption levels of light drinkers demonstrate a high degree of stability. However, the consumption levels of heavy drinkers demonstrate less stability, especially over a long time period. Heavy drinkers significantly reduced reported levels of alcohol consumption on both measures after the first test, suggesting a regression to the mean effect or the possibility of unintended intervention effects due to repeated measurement of drinking behaviour. PMID- 1884666 TI - A comparison of two treatment interventions aimed at lowering anxiety levels and alcohol consumption amongst alcohol abusers. AB - This study compared the differential efficacy of anxiety management and relaxation training - with respect to their impact on anxiety levels and alcohol consumption amongst people attending an Alcohol Treatment Unit. It was hypothesised that anxiety management would have a greater effect on the outcome measures than would relaxation training and that the effect on alcohol consumption would be moderated by changes in the clients' perceptions of their ability to control their drinking. The two treatment groups were found to significantly reduce self-reported anxiety with the anxiety management group being more effective than relaxation training. They had no impact on alcohol consumption. PMID- 1884667 TI - 'Unstandard' ways of answering standard questions: protocol analysis in alcohol survey research. AB - The purpose of this paper is to discuss the history and development of protocol analysis as a useful approach for survey research in the alcohol field, and to describe the results of a pilot study which used protocol analysis to assess the recall strategies used for four standard alcohol questions commonly used in surveys. Twenty-nine subjects were interviewed and asked to think aloud their responses to four alcohol items: frequency of drinking, average quantity, frequency of drinking over 5 drinks, and frequency of drunkenness. Results indicate that respondents most often used anchoring and adjustment and context strategies to arrive at their answers. Suggestions for facilitating the use of specific strategies during an interview are given. PMID- 1884668 TI - Levels of opioid physical dependence in heroin addicts. AB - The levels of opioid physical dependence in a group of long-term heroin addicts were ascertained by measuring the severity of the opioid withdrawal syndrome before and after pharmacological challenge with either 0.4 mg naloxone or placebo. Prior to challenge, patients manifested some subjective symptoms but few objective signs of opioid withdrawal. Patients who received placebo (n = 18) showed a significant increase in the mean score on one of three rating scales used to assess opioid withdrawal. Patients who received naloxone (n = 58) showed significant increases in mean scores on all three rating scales, but this was due primarily to increases observed in a minority of patients. Sixty-one percent of patients failed to manifest clinically significant changes in subjective symptoms, and 74% of patients failed to manifest clinically significant changes in objective signs of opioid withdrawal following naloxone administration. The results suggest that a substantial subgroup of heroin addicts are able to use opioids regularly while maintaining relatively low levels of physical dependence. PMID- 1884669 TI - Primary and secondary depression in alcoholism--clinical features and family history. AB - One hundred thirty-six alcoholic inpatients were studied with regard to the association between alcoholism and depression. They fell into three groups: primary depression, secondary depression and non-depressive alcoholism. The main results obtained are as follows: (1) Depression was found in 46 patients (33.8%) in the present or past history; 13 were regarded as primary depression and 33 as secondary depression. (2) The clinical symptoms and the background of the primary group resembled those of endogenous depression. (3) The clinical features, including the duration of depressive episodes in the secondary depression group differed from those in the primary group. (4) No statistically significant differences were noted as to the rates of family-history of alcoholism and depression among the three groups. Clinical and biological differences between the primary and secondary groups were discussed on the basis of these results. PMID- 1884671 TI - Abuse liability studies of opioid agonist-antagonists in humans. AB - Prediction of the abuse liability of a drug before it reaches the market is complicated by the fact that there are many factors that influence the actual abuse of a drug. Laboratory methods used in humans to assess the abuse liability of the opioids are reviewed and illustrative studies of morphine and the agonist antagonist opioids, pentazocine, butorphanol, nalbuphine and buprenorphine, are presented. Three assessment methods, subjective effect measurement, self administration and drug discrimination, provide information relevant to measuring reinforcing efficacy, a major determinant of the degree to which a drug is sought and self-administered by abusers. Physical dependence capacity, which can contribute to sustained drug use, is evaluated in direct addiction and substitution/suppression studies. Withdrawal precipitation studies measure antagonist activity which might limit abuse. The results of testing the agonist antagonist opioids are generally consistent across these various methods and consistent with historical experience with these drugs, suggesting that these methods are useful in predicting abuse liability of novel opioids. PMID- 1884670 TI - Alcohol drinking and cigarette smoking: an exploration of the association in middle-aged men and women. AB - The association of alcohol and cigarette consumption was explored among 13,673 black or white persons aged 40-49 years, who received check-ups from mid-1979 to 1985. Alcohol use was strongly associated with number of cigarettes smoked per day, but not with tar-yield, mentholation and presence of filters. Duration of cigarette use, frequency and depth of inhalation, proportion of cigarette smoked and greater time from arising to first cigarette were significantly related to alcohol use in some but not all race-sex groups. Among smokers who consumed alcohol, liquor drinkers smoked the most cigarettes per day and wine drinkers the least. Thus, the association between alcohol drinking and cigarette smoking is strong in middle-aged persons but there are race- and sex-related disparities when specific aspects of smoking behaviour are considered. PMID- 1884672 TI - [24-hour blood pressure profile: reproducibility of automatic ambulatory measurement]. AB - Twelve patients (8 males, 4 females; mean age 53 [43-60] years) who were undergoing rehabilitation treatment after myocardial infarction were studied to ascertain the reproducibility of ambulatory automatic blood pressure measurements. All were in the last stage of a rehabilitation programme (tolerance to ordinary activity; symptom-free exercise at 75 W). Within two weeks 2, 3 or 4 blood-pressure profiles over 24 hours (total of 32 readings) were obtained by automatic measurement and the records and mean values were compared. Single mild stresses, such as gymnastic exercise or visit to the doctor, were identifiable on the records, but did not alter the overall profile or mean values. Normotensives, hypertensives and borderline hypertensives had 24-hour profiles which were nearly identical with regard to the curve "envelope", day-night profile and mean values in the individual patients. Mean values of diastolic and systolic pressures day by day in each patient showed no deviations greater than 5 mm Hg. Therapeutic measures were recognizable by parallel fall of the curve "envelope", as well as by a reduction in mean value.--At least in these selected patients a single 24 hour profile would in principle have sufficed to describe blood pressure behaviour. PMID- 1884673 TI - [Morphological and toxicological findings after intravenous injection of metallic mercury]. AB - At the autopsy of a 25-year-old man who had died from combined morphine and cocaine intoxication, depositions of metallic mercury were incidentally found in the myocardium of the right ventricular septum and posterior wall. Deposits, toxicologically identified as mercury, were also found radiologically and histologically in the lungs. All these deposits were probably the result of intravenous injections of mercury many months previously, as is known to be done occasionally by addicts. Judging by the histological picture the greatest proportion of the mercury collected in the right ventricular cavity after injection, a smaller amount by embolization in the small pulmonary arteries. The mercury spheres which came to lie in the right ventricle then penetrated into the myocardium, moving outward and causing a chronic and partly transmural inflammatory response. PMID- 1884674 TI - [Methotrexate in the therapy of primary biliary cirrhosis]. AB - In a pilot study 5 females with primary biliary cirrhosis (PBC), histological stages I-III, were treated with methotrexate (7.5-15.0 mg by mouth weekly) for 15 months. Pruritus and fatigue decreased in 3 patients and cholestyramine could be reduced or discontinued. The concentration of alkaline phosphatase decreased significantly until the 6th month of treatment (P less than 0.002), but only after the methotrexate dosage had been increased to 15 mg weekly. However, the improvement in cholestasis parameters persisted until the end of the period of observation in only 3 patients in stages I and II. In only one case, initially in stage III with increased serum bilirubin concentration of 3.5 mg/dl, was there a change in the histological stage, to stage IV, after treatment. These preliminary results indicate that methotrexate can influence the symptoms and cholestasis enzymes in the early stages of PBC. Controlled studies should therefore only be conducted on anicteric patients in an early stage of the disease. PMID- 1884676 TI - [Ulcerative colitis: quality of life after surgical therapy]. PMID- 1884675 TI - [Recurrent thromboembolism due to increased acetylsalicylic acid-resistant platelet aggregation]. AB - A 49-year-old man had for 30 years suffered from severe recurrent thromboembolism with leg-vein thrombosis, pulmonary emboli, mesenteric infarction, cerebrovascular accident, cerebral vein thrombosis, portal vein thrombosis and femoral artery occlusion requiring leg amputation. In addition to moderately increased clotting activation with single-fold positive demonstration of fibrin monomers and a D-dimer concentration of 1 mg/l platelet aggregation was increased and could not be influenced by aspirin, 300 mg daily. Despite aspirin there were recurrent transitory attacks of cerebral ischaemia. Fibrin monomers were threefold positive and D-dimer concentration was increased to 4 mg/l (elevated clotting activation). Ticlopidine administration (250 mg daily) reduced adenosine diphosphate-induced platelet aggregation by 30% without effect on collagen induced platelet aggregation. In parallel to these changes the patient's general condition clearly improved: fibrin monomers were no longer demonstrated and the D dimer level fell to 0.5 mg/l. PMID- 1884677 TI - ["Late fever attacks" after malarial infection]. PMID- 1884678 TI - [Endoscopic Doppler sonography]. PMID- 1884679 TI - [Renal effects of conversion enzyme inhibitors]. PMID- 1884680 TI - [Prednisone lessens incidence of recurrence after severe asthma attack]. PMID- 1884681 TI - [Lymphoid cell infiltration into the pancreas of C57BL/6J mice]. AB - Peri-insular lymphoid infiltrations were observed in nondiabetic C57BL/6J mice. The type of infiltrating cells was determined by direct immunoperoxidase technique. A larger part of lymphoid cells did not show reaction with a goat antimouse IgG Rh conjugate. Intensive hyperplastic reaction and the presence of many immunoglobulin producing cells were observed in the lymph nodes adjoining the pancreas. Probably the observed infiltrations in the pancreas of nondiabetic C57BL + 6J mice were composed mainly of T lymphocytes, belonging to T helper subpopulation. PMID- 1884682 TI - [Changes in the electrophysiological parameters of hypertensives under the influence of therapeutic swimming]. AB - Studies were carried out on patients with hypertension I and II stages to examine the influence of therapeutic swimming on cerebral activity and heart function. The authors investigated 30 persons (mean age of 48.5 +/- 9.5 years) divided into 2 groups: first--experimental including 20 subjects, who participated in a course of therapeutic swimming (according to our methods) for a period of 4 months and second--control, composed of 10 persons, who did not swim. Electroencephalograms and electrocardiograms were recorded from subjects of both groups before and after 4 months of swimming as simultaneously with this blood pressure was measured several times. The results showed that therapeutic swimming affected favourably brain bioelectrical activity (improved regulation and modulation of the rhythm, reduced dysrhythmia and did not increase the number of pathological waves) as well as cardiovascular system of the examined persons with hypertension of the experimental group as statistically significant lowering of blood pressure was induced, while the investigated parameters showed opposite reactions in the persons of the control group. On the basis of positive changes in the investigated parameters the therapeutic swimming is recommended to be included in the complex the therapy of the persons suffering from hypertension I and II stages. PMID- 1884683 TI - [The morphology of the glial cells in the inferior olivary complex of ground squirrels (Citellus citellus L.). I. Oligodendrocytes]. AB - The morphological characteristics of oligodendrocytes in the lower olivary complex of ground squirrels at various ages were studied by light and electron microscopes. On the basis of an analysis on thick sections, stained with toluidine blue, it was established that nuclei of these cells were smaller and darker in comparison with those of astrocytes. The mean oligodendrocytes, located in perineuronal, perifascicular, perineuronal-perifascicular, interfascicular, perivascular position or freely situated, predominated in the neuropile of the lower olivary complex. Changes in their ultrastructure were investigated during advancement of age and during the process of aging. An increase in the number of heterogeneous dense bodies were found as well as the presence of lipid-pigmented granules with crystal-like brightening. The connection of oligodendrocyte growth with myelin sheath of axons. PMID- 1884684 TI - [The mixed-function oxidase activity in male rats with a pancreatectomy]. PMID- 1884685 TI - [Anthocyanins and analgesics or a possibility of a new analgetic combination]. AB - Studies were carried out on male white mice to investigate the influence of cantocyans on pain both singly and in combination with the classic analgetics. The following tests were used: the test for narcotic analgetics "hot plate" and the analgetic morphine, administered subcutaneously in sub- and nonanalgetic doses (10 and 5 mg/kg of body mass respectively); the test for nonnarcotic analgetics-chemical peritoneal stimulation with 3% of acetic acid and the analgetic analgin, administered subcutaneously in a nonanalgetic dose (100 mg/kg of body mass). The results from the experiments showed that antocyans did not possess its own analgetic effect in both of the experimental models. However their combination with morphine and analgin, administered in noneffective analgetic doses, caused manifested analgetic effect of the combinations in all used doses of antocyans (50, 100 and 200 mg/kg of body mass). The possibility for therapeutic usage of analgetic combinations of antocyans and narcotic and nonnarcotic analgetics is discussed. PMID- 1884686 TI - [Cytochrome B5--its molecular characteristics and biochemical significance]. PMID- 1884687 TI - [The hypertensive effect of vasopressin administered into the median eminence of the hypothalamus in rats]. AB - Data about direct effect of vasopressin (VP) on the central arterial pressure (AP) orientated us to investigate the effect of its local administration in the median eminence (ME) of the hypothalamus in rats. For this purpose VP was administered in ME under micropellet form. AP was measured indirectly on the tail of rats up to 96th hour after operation. After implantation of VP there was an elevation of AP with maximum in the first hour, which was statistically significant (p less than 0.01). Identical manipulation (sham operation) was performed to control the lesion effect. Transitory lowering of AP with maximum in the first hour was also established and it was statistically significant (p less than 0.001), For exclusion a nonspecific systemic effect of VP the same dose was administered in the parietal cortex, during which transitory and short-lasting reaction occurred in the first hour after the operation. The data indicate that the peptide, administered in ME under micropellet form, could induce a longlasting hypertensive effect. PMID- 1884688 TI - [The significance of biologically active substances in regulating local vascular tonus]. PMID- 1884689 TI - [The mechanisms of the cytotoxic action of hyperthermia]. AB - A review of literature on the most significant aspects of molecular and cellular effect of hyperthermia is presented. A critical evaluation of the acceptability of several hypotheses for biochemical mechanisms of cytotoxic action of hyperthermia is made. A special attention is paid to a molecular model of thermic induced cellular death, proposed by Roti-Roti. In conclusion it is generalized that the thermic induced changes in the chromatin are those, which are involved in realization of DNA damage and which process, if not completely, at least partially in the basis of thermic induced cellular death. PMID- 1884690 TI - [The effect of the intracerebroventricular administration of vasopressin on the arterial pressure and heart rate of Brattleboro and Long-Evans rats]. AB - Vasopressin (VP) was administered in the lateral cerebral ventricles of homozygous rats with congenital diabetes insipidus of Brattleboro (BB) strain as well as of normal animals of Long Evans strain (LE). The following parameters were studied: the latent period for achievement of maximal pressor response in seconds (LP), absolute value of the increase in arterial pressure in comparison with the initial V mmHg (delta AP) and cardiac frequency (CF). The initial values of AP in BB were lower than those values found in LE (BB-9, 10 +/- 0.57 kPa; LE 11, 31 +/- 0.53 kPa; p less than 0.01, while CF showed higher values in BB (350 +/- 8.5 min-1); LE (321 +/- 10 min-1); p less than 0.05. VP, administered intraventricularly, induced quick transitory elevation of AP in both groups, which did not differ substantially both in respect to LP (BB-55 +/- 11 s; LE-43 +/- 6.9) and also in respect to delta AP (BB-3.64 +/- 0.34; LE-3.14 +/- 0.62). CF was not changed in BB (347 +/- 8.9), while it was slightly increased in LE (334 +/- 11). The data show that exogenously administered VP affect the central VP dependent mechanisms for regulation of AP in the same way in both groups of rats. PMID- 1884691 TI - Muscle biopsy: what have we learnt in the last 20 years? PMID- 1884692 TI - Arthroscopy: a chance to cut or cure? PMID- 1884693 TI - Could the worms have turned? PMID- 1884694 TI - Osteochondritis dissecans of the tarsocrural joint: results of treatment with arthroscopic surgery. AB - The technique and results of arthroscopic surgery for the treatment of osteochondritis dissecans in 318 tarsocrural joints in 225 horses are reported. Of the 225 horses, 154 were racehorses or intended for racing. Arthroscopic surgery was an effective technique for treating osteochondritis dissecans of the tarsocrural joint. The overall functional ability and cosmetic appearance of the limbs were excellent. Post surgical follow-up information was obtained for 183 horses, of which 140 (76.5 per cent) raced successfully or performed their intended use following surgery. Of the remaining 43, 11 were considered to still have a tarsocrural joint problem, 19 developed other problems precluding successful performance, eight were considered poor racehorses without any lameness problems identified, three were killed because of septic arthritis and two died from other causes. There was no significant effect of age, sex or limb involvement on the outcome. The size of the intermediate ridge lesions had no effect on prognosis but the presence of degenerative or erosive changes in the articular cartilage significantly decreased the prognosis. The synovial effusion resolved in 117/131 racehorse joints (89.3 per cent) and 64 of 86 non-racehorse joints (74.4 per cent) with follow-up. The outcome for synovial fluid resolution was significantly inferior for lesions of the lateral trochlear ridge of the talus or medial malleolus of the tibia compared to distal intermediate ridge lesions. There was no significant relationship between resolution of effusion and successful performance outcome. PMID- 1884695 TI - Arthroscopic removal of osteochondral fragments of the palmar/plantar aspect of the metacarpo/metatarsophalangeal joints. AB - This paper presents the results of arthroscopic surgery in 42 Standardbred trotters and three Finnish horses. Forty-five horses were operated on. The age range was one to seven years; 73 per cent of the horses were three years old or younger. Horses showed a variety of clinical signs ranging from moderate to severe lameness at slow speeds, to obscure lameness manifesting only at high speeds. Synovial effusion of the fetlock joint was rare. In this series, 44 horses that had Type I fragments and one horse that had Type III fragments were operated on. Of the 45 horses operated on, 23 (51 per cent) returned to speed training in three months and 41 (91 per cent) returned to speed training in six months. Three of 45 (6 per cent) were lame three months after the surgery when the trainer attempted to start speed training. One of those was sound six months after the operation. The remaining two (4 per cent) stayed lame due to a lesion in the affected joint. Two of 45 (4 per cent) discontinued training for other reasons. The horse with Type III fragments returned to speed training in three months. PMID- 1884696 TI - Relative incidence of dorsal metacarpal disease in young Thoroughbred racehorses training on two different surfaces. AB - The relative incidence of dorsal metacarpal disease was examined in two groups of Thoroughbred racehorses training on dissimilar surfaces (dirt and wood fibre). The horses and training methods appeared to be similar. The incidence of disease was significantly greater in the group training on dirt. There was no significant difference in the age distribution of incidence between the two groups and there was no association of incidence with sex or age within the training group. The number of fast miles worked by the two groups prior to the onset of dorsal metacarpal disease was lower in the group training on dirt. PMID- 1884697 TI - Clinical evaluation of poor performance in the racehorse: the results of 275 evaluations. AB - A clinical sports medicine evaluation was applied to 275 racehorses with a history of poor racing performance. The poor performance evaluation included a) general physical examination and basic laboratory screening; b) respiratory examination including auscultation, thoracic radiographs, ventilation-perfusion lung scintigraphy and upper airway endoscopy at rest and during maximal treadmill exercise c) examination of the musculoskeletal system including lameness examination, video gait analysis at high speed, post exercise serum chemistry to identify obvious as well as sub-clinical myopathies, high detail radiography and nuclear scintigraphy; d) cardiac examination including auscultation, electrocardiographic analysis during strenuous exercise and when indicated, echocardiography; and e) a standardised exercise stress test entailing the measurement of oxygen consumption, carbon dioxide production, venous blood lactate concentration and heart rate during sequentially increasing running speeds on the high speed treadmill. The choice of diagnostic methodologies utilised were tailored to each individual in order to determine most efficiently the abnormalities contributing to inadequate racing performance. The results of this clinical evaluation showed that 1) many of the diagnoses were subtle requiring the use of sophisticated diagnostic equipment including scintigraphy and dynamic evaluation of the horse exercising on the high speed treadmill and 2) 84 per cent of the horses were diagnosed as suffering from more than one problem leading to the supposition that inadequate athletic performance is often caused by a constellation of abnormalities requiring a comprehensive approach to diagnosing decreased athletic capability. PMID- 1884698 TI - Assessment of the breeding prognosis of mares using paired endometrial biopsy techniques. AB - Paired endometrial biopsy samples were taken from 530 subfertile mares, before and after treatment (where indicated) and a period of sexual rest. Prognoses were made after each biopsy (Categories 1A-4A before treatment and Categories 1B-4B after treatment), using histopathological criteria similar to those described by Kenney and Doig (1986). Eighty-seven per cent of the mares were assigned to first biopsy prognosis Category 3A. The second biopsy prognosis produced a more even population distribution (10, 47, 40 and 3 per cent respectively for Category 1B, 2B, 3B and 4B mares). First biopsy Category 3A and 4A mares produced mean foaling rates of 51 and 40 per cent respectively. None of the 14 second biopsy Category 4B mares delivered a live foal (12 were barren, one aborted and one suffered early foetal death). This study supports the hypothesis that a breeding prognosis assigned on the basis of two endometrial biopsy samples, taken before and after specific uterine treatment, where indicated, which takes into consideration the mare's ability to respond to treatment, is likely to be more accurate than one assigned after a single biopsy sample. PMID- 1884699 TI - The effect of age and parity on the development of equine chronic endometrial disease. AB - The results of a retrospective analysis of 3,804 endometrial biopsy specimens collected from non-pregnant mares during the course of routine equine stud farm practice demonstrates a significant and practically useful correlation between the severity of chronic degenerative endometrial disease (CDE) diagnosed and age of mare at the time of examination. There were significant correlations between the number of foals born and the mares' barren years prior to biopsy and the severity of CDE, but the differences were not sufficiently large to be useful. Correlations between the severity of chronic infiltrative endometritis (CIE) and age or pre-biopsy parity were minimal. The results suggest that using similar histopathological criteria to those used by Kenney and Doig (1986), mares up to nine years of age should have no signs of CDE, mares up to 13 years of age should have no more than mild signs, mares up to 15 years of age should have no more than moderate signs and mares aged 17 years or older are likely to have severe signs. We believe that these guidelines are a useful, objective aid for formulating a breeding prognosis. PMID- 1884701 TI - Equine helminth infections: control by selective chemotherapy. AB - A programme of selective anthelmintic therapy was used in a herd of 31 horses. Faecal egg counts were done during the months of September, November, January, March, May and the following September. Horses with greater than or equal to 100 eggs per gram (epg) were treated with ivermectin, and those with less than 100 epg were not treated. The criteria for adequate internal parasite control in the herd was a median herd faecal egg count of less than or equal to 100 epg. Effectiveness of selective therapy was assessed by faecal egg count after nine months of treatment and was determined to be adequate when a median herd egg count of 0 epg was obtained. However, on returning from pasture the following September, median herd egg count had risen to 325 epg. A statistically significant correlation was seen in the paired September faecal egg counts of the horses in that initial September faecal egg count was predictive for the following September. Initial September faecal egg count was related to the number of anthelmintic treatments required during the period of selective therapy, whereas age of horse was not. We propose that faecal egg counts be incorporated into strategic anthelmintic programmes as an economical tool for identifying and targeting herd members predisposed to shedding elevated numbers of helminth eggs. PMID- 1884700 TI - Titrimetric determination of muscle buffering capacity (beta mtitr) in biopsy samples. AB - In vitro titration of muscle homogenates has been used to assess muscle buffering capacity (beta mtitr) in a variety of species. In the present study, factors likely to affect the estimation of beta mtitr were investigated. Also, values of beta mtitr from normal Thoroughbred horses are presented. A non-linear titration curve was obtained with addition of HCl to muscle homogenates. As a result, beta mtitr is expressed as the mumol H+ required to change the pH of 1g of dry muscle or wet muscle from 7.1 to 6.5. An effect of dilution on the initial pH was found below 40 mg wet muscle per ml homogenising reagent (10 mg dry muscle per ml) and on beta mtitr below 10 mg wet muscle. As a result, 40 mg wet muscle or 10 mg dry muscle per ml was chosen as the minimum concentration for determination of beta mtitr. Incubation of homogenates up to 60 mins did not affect beta mtitr significantly. As a mean, beta mtitr in wet muscle was approximately 25 per cent higher compared to dry muscle. The beta mtitr of dry muscle was increased by approximately 18 per cent when HCO3- was added in an amount equivalent to the calculated HCO3- content of wet muscle at rest. The homogenisation process resulted in complete loss of adenosine triphosphate and phosphocreatine with only small changes in adenosine diphosphate and adenosine monophosphate. It was concluded that the estimates of beta mtitr did not include any contribution from 'dynamic' buffering via rephosphorylation of adenosine diphosphate by phosphocreatine, and in dry muscle it was accounted for mainly through physico chemical buffering by phosphates, proteins and dipeptides. beta mtitr determined in biopsy samples of muscle from 20 Thoroughbred horses ranged from 100.8 to 131.8 mumol H+/g dry muscle pH 7.1 to 6.5 (mean 121.2, sd +/- 7.4). PMID- 1884702 TI - Characterisation and distribution of epidermal growth factor receptors in equine hoof wall laminar tissue: comparison of normal horses and horses affected with chronic laminitis. AB - Epidermal growth factor (EGF) receptors were detected in plasma membrane preparations of equine hoof wall laminar tissue at concentrations comparable to that of equine liver. Scatchard analysis of the equilibrium binding data suggested the presence of two classes of EGF binding sites in most of the controls (plasma membranes from clinically normal horses); a high-affinity class and a more numerous low-affinity class. The dissociation constant of the low affinity class of EGF-specific receptors (KD = 1 x 10(-9)M) is in reasonable agreement with other values established for the EGF receptor. The variability between individual estimates for the KD of the high-affinity receptor class precluded an accurate estimate for those sites. A possible explanation is discussed. The high-affinity binding sites were uniformly absent in plasma membranes prepared from horses affected by chronic laminitis. Autoradiographic analysis localised the EGF receptors primarily to the secondary epidermal laminae, with an apparent greater density over the proliferative basal keratinocytes. Little label was associated with the dermal or the keratinised primary epidermal laminae. Tissue from horses with chronic laminitis had EGF receptors located uniformly over the hyperplastic epidermal keratinocytes. These data suggest that an EGF-mediated response may be involved in the hyperproliferative response that is characteristic of chronic laminitis. PMID- 1884703 TI - Muscle characteristics in Thoroughbreds of different ages and sexes. AB - Muscle biopsies were taken from the middle gluteal muscle in 163 healthy Thoroughbreds aged one to six years. The horses were separated according to sex and divided into four different age groups (one, two, three and four to six years). Muscle biopsies were analysed for fibre type (I, IIA and IIB), and the enzyme activities of citrate synthase, 3-OH-acyl-CoA dehydrogenase, lactate dehydrogenase and hexokinase were measured. The percentage of Type I fibres of all horses increased with age, irrespective of sex (from 9 to 16 per cent). The percentage of Type IIA fibres varied with age and sex, increasing in stallions from 34 to 53 per cent and in mares from 27 to 45 per cent, respectively. Correspondingly, the proportion of Type IIB fibres decreased with age and differed between sexes (stallions from 56 to 29 per cent and mares from 65 to 40 per cent) Muscle oxidative capacity increased with age as indicated by significant increases in the activities of citrate synthase (from 32 to 67 mmol/kg/min) and 3-OH-acyl-CoA dehydrogenase (from 20 to 34 mmol/kg/min). The activity of hexokinase increased with age (from 2.4 to 4.8 mmol/kg/min), whereas the activity of lactate dehydrogenase decreased (from 1,754 to 1,444 mmol/kg/min). No differences were seen between stallions and mares in enzyme activities. This study shows that age is one factor influencing enzyme activities, the percentage of Type I fibres and the Type IIA/IIB ratio in M. gluteus medius of Thoroughbreds, and that stallions have a higher Type IIA/IIB ratio compared with mares. PMID- 1884704 TI - Antithrombin III activity in horses with colic: an analysis of 46 cases. AB - Antithrombin-III (AT-III) activity was measured at the time of admission in 46 horses referred with colic. Differences in AT-III activities between animals treated medically or surgically and survivors or non-survivors were compared. The mean AT-III values for the horses treated medically (76.2 per cent), surgical survivors (69.5 per cent) and surgical non-survivors (55.9 per cent) were significantly different from the reference value for healthy adults (92 to 108 per cent). The mean AT-III activity of the survivors was significantly (P less than 0.01) greater than that of the nonsurvivors. The majority of the survivors (11 to 13 horses) had AT-III activities exceeding 60 per cent of normal, whereas that of 10 of the 14 non-survivors was less than 60 per cent of normal. There was an apparent distinction between the survivors and non-survivors at approximately 60 per cent of normal AT-III activity. PMID- 1884705 TI - Anatomical and functional communications between the synovial sacs of the equine stifle joint. AB - The anatomical and functional communications of the synovial sacs of the equine stifle joint were evaluated in 50 stifle joints of 25 horses. Femoropatellar joint (FPJ) sacs were injected with 50 ml of gelatin-based dye and horses were then walked for 50 m. Horses were subsequently killed, the stifle joints dissected and the location of the dye recorded. Twenty-three horses (46 joints) had clinically normal stifle joints and in this group, anatomical communications of the stifle joints were bilaterally symmetrical in each horse. In 15 of these 23 horses (65 per cent), direct anatomical communication between the FPJ sac and the medial sac of the femorotibial joint (FTJ) was demonstrated. The FPJ sac communicated with both the medial and lateral sacs of the FTJ in four of these 23 horses (17.5 per cent). There were no anatomical communications between the FPJ sac and either sac of the FTJ in the remaining four horses (17.5 per cent). Functional communication, which was established by finding dye in the FTJ sacs were anatomical communication with the FPJ sac existed, was demonstrated in 14 of 19 horses (74 per cent). Two horses were affected with degenerative joint disease of one stifle joint. In both of these joints the FPJ sac communicated with both the medial and lateral FTJ sacs. This distribution was different from that of the contralateral joint. When performing intra-articular anaesthesia of equine stifle joints, each synovial sac needs to be injected separately to ensure that anaesthesia of the appropriate synovial sac is obtained. PMID- 1884706 TI - Exercise induced hormonal and metabolic changes in Thoroughbred horses: effects of conditioning and acepromazine. AB - Nine Thoroughbred horses were assessed to determine the normal response of insulin, glucose, cortisol, plasma potassium (K) and erythrocyte K through conditioning and to exercise over 400 and 1,000 m. In addition, adrenaline, noradrenaline, cortisol, plasma K, erythrocyte K and L-lactate concentrations were evaluated in response to maximal exercise with and without the administration of acepromazine. Conditioning caused no obvious trends in plasma K, erythrocyte K, insulin or glucose concentration. Serum cortisol increased (P less than 0.05) from the initial sample at Week 1 to Weeks 4 and 5 (attributed to a response to training), and then decreased. During conditioning, three horses had low erythrocyte K concentrations (less than 89.3 mmol/litre). Further work is needed to define the significance of low erythrocyte K concentrations in the performance horse. In all tests maximal exercise increased plasma K, glucose and cortisol concentrations, whereas insulin and erythrocyte K concentrations decreased. Thirty minutes following exercise, plasma K and erythrocyte K concentrations returned to resting values; whereas glucose and cortisol concentrations continued to increase and the insulin concentration also was increased. The magnitude of the changes varied for pre-conditioned vs post conditioned exercise tests and the duration of exercise. The administration of acepromazine prior to exercise over 1,000 m failed to alter the circulating noradrenaline and adrenaline concentrations in anticipation of exercise or 2 mins following exercise. Acepromazine administration, however, did cause lower L lactate concentration 2 mins (P less than 0.03) and 30 mins (P less than or equal to 0.005) following exercise. Also, erythrocyte K showed a delayed return to baseline levels at 30 mins post exercise. Further evaluation of these trends may help explain the beneficial role acepromazine plays in limiting signs of exertional rhabdomyolysis when administered prior to exercise. PMID- 1884707 TI - Hepatolithiasis in an Arabian mare. PMID- 1884708 TI - Self-reported health and well-being amongst night security guards: a comparison with the working population. AB - The present study sought to relate the well-being of night workers to that of the working population in general. One hundred and ninety-seven male permanent night security guards were interviewed with regard to the occurrence of various symptoms during the previous 12-month period. The results were compared with the results from similar interviews with a representative national sample of males (n = 1769) in the Swedish workforce. An age standardized morbidity ratio was computed with control for various background variables. The results showed that the security guards had a 2-3 times higher occurrence of sleep disturbances and fatigue than the national sample. Among the variables not differing from the national sample were gastrointestinal problems, headache, nervous problems, depression, nausea, diarrhoea, and haemorrhoids. It was concluded that sleep/wake disturbances are considerably more usual in permanent night security guards than in the working population as a whole. PMID- 1884709 TI - Worker selection of safe speed and idle condition in simulated monitoring of two industrial robots. AB - Industrial robots often operate at high speed, with unpredictable motion patterns and erratic idle times. Serious injuries and deaths have occurred due to operator misperception of these robot design and performance characteristics. The main objective of the research project was to study human perceptual aspects of hazardous robotics workstations. Two laboratory experiments were designed to investigate workers' perceptions of two industrial robots with different physical configurations and performance capabilities. Twenty-four subjects participated in the study. All subjects were chosen from local industries, and had had considerable exposure to robots and other automated equipment in their working experience. Experiment 1 investigated the maximum speed of robot arm motions that workers, who were experienced with operation of industrial robots, judged to be 'safe' for monitoring tasks. It was found that the selection of safe speed depends on the size of the robot and the speed with which the robot begins its operation. Speeds of less than 51 cm/s and 63 cm/s for large and small robots, respectively, were perceived as safe, i.e., ones that did not result in workers feeling uneasy or endangered when working in close proximity to the robot and monitoring its actions. Experiment 2 investigated the minimum value of robot idle time (inactivity) perceived by industrial workers as system malfunction, and an indication of the 'safe-to-approach' condition. It was found that idle times of 41 s and 28 s or less for the small and large robots, respectively, were perceived by workers to be a result of system malfunction. About 20% of the workers waited only 10 s or less before deciding that the robot had stopped because of system malfunction. The idle times were affected by the subjects' prior exposure to a simulated robot accident. Further interpretations of the results and suggestions for operational limitations of robot systems are discussed. PMID- 1884710 TI - Human strength capabilities during one-handed maximum voluntary exertions in the fore and aft plane. AB - Maximal static strengths were determined for one-handed exertions in all directions in the fore and aft plane. Data from 12 males and 10 females (mean age 30.7 yrs, standard deviation (SD) = 8.9 yrs, n = 22) were obtained with handle heights of 1.0 and 1.75 m. Twelve of the subjects also performed two-handed exertions at the same handle heights. The ratio of mean strengths of females to that of males ranged from 0.50 to 0.83 (for absolute forces) and from 0.63 to 1.00 for forces normalized to body weight. The ratios of one-handed to two-handed strengths ranged from 0.64 to 1.04. Two-handed strengths commonly exceeded one handed strengths at the lower handle height, but showed fewer significant strength differences (p less than 0.05) according to direction at 1.75 m. Both female/male and one-handed/two-handed strength ratios were found to be dependent on direction of exertion and handle height. The observed strength dependencies upon number of hands (one or two-handed), direction of exertion, handle height and sex are discussed. The strength data have implications for use in biomechanical models and task analysis. PMID- 1884711 TI - The effect on sitting posture of a desk with a 10 degree inclination for reading and writing. AB - A pilot study was carried out on 10 subjects to examine the effect that a desk with a 10 degree inclination had on their sitting posture while reading and writing. A continuous recording of the subjects head and trunk positions was made. Each subject was studied during two periods of 1.5 h on different days. The subject worked at a flat desk on the first day and at a desk with a 10 degree inclination on the second. On average, the position of the head in the sagittal plane was found to be 6 degrees more erect and the position of the trunk 7 degrees more erect when working at a desk with a 10 degree inclination than when working at a flat desk. The maximal decrease in load observed on the cervical spine was 35% and on the thoracic spine 95%. The angle between the head and the trunk did not change significantly when using an inclined desk. Differences in posture in the frontal plane were not observed in this study. PMID- 1884712 TI - Efficiency and effectiveness of stoop and squat lifting at different frequencies. AB - The study investigated the effects of frequency (10 and 20 lifts/min) and technique (squat and stoop) of repetitive lifting of a barbell (19 kg) on the relationship between mean power output (Pm) and energy cost in 9 male power lifters. Oxygen uptake (VO2) was measured directly and continuously and power output was deduced from film analysis using an inverse dynamic analysis. Power output and VO2 were significantly greater for squat than for stoop lifting at the same frequency. The mechanical efficiency (ME), defined as Pm divided by the energy equivalence of VO2, increased from 12% at rate 10 to 18.5% at rate 20, but there was no significant difference between the two techniques. The effectiveness (EF), defined as the productive external power output (only work done on the barbell) divided by the energy equivalence of VO2, was significantly higher for the stoop lift than for the squat lift. EF is judged as a more useful measure than ME for characterizing the relative energy cost of a lifting task. PMID- 1884713 TI - Structural determinants of the psychosocial work environment: introducing technology in the work stress framework. AB - To extend current models of psychosocial work stress research into organizational structure, technology is introduced. An exploratory model is developed combining research from ergonomics, epidemiology, and organizational science. It is hypothesized that technology influences a worker's health by structuring the job, and the relationship between the job and a worker's health is mediated by attitudes at work. To test the model, data are used from a 1978 NIOSH survey of postal workers sorting mail (N = 4903). Path analysis shows technology is indirectly associated with job satisfaction and psychosomatic symptoms by how it structured the job. A machine-paced technological system of work is associated with greater job demands, less control in the job, and less co-worker support but not with supervisor support. The implications of this model for prevention strategies at the workplace are discussed suggesting that influencing supervisor support is the most effective way to affect a person's job satisfaction and level of psychosomatic symptomology. PMID- 1884714 TI - The role of technical, biological and pharmacological factors in the laboratory evaluation of anticonvulsant drugs. IV. Protective indices. AB - Calculation of protective or therapeutic indices is widely used in primary and secondary screening for drugs with selective anticonvulsant activity. The protective index is the median minimal 'neurotoxic' dose, TD50, divided by median effective dose, ED50. TD50s are usually determined by tests, such as the rotarod test or the chimney test, for quantification of 'minimal neurological deficit', such as motor impairment, while median effective doses are commonly determined in the maximal electroshock seizure (MES) test or the s.c. pentylenetetrazol (PTZ) seizure test in mice or rats. For antiepileptic drug development, it has been proposed previously that only compounds with an estimated protective index of at least 5 should proceed to further evaluation. However, various technical, biological and pharmacological factors can influence anticonvulsant or 'neurotoxic' potencies and thereby protective indices. In order to reevaluate the value of protective indexes in the prediction of drugs with selective anticonvulsant action, protective indices were determined for various clinically used antiepileptic drugs in standardized seizure tests, i.e. MES and s.c. PTZ tests in mice and rats, as well as in seizure threshold tests. For most drugs, similar TD50s were determined in the rotarod and chimney test. When protective indices were calculated for the different seizure models, only few drugs reached an index of 5 (some not even reaching an index of 2) in the traditional MES or s.c. PTZ tests in mice and rats. In contrast, using anticonvulsant doses determined by seizure threshold tests, the 5 primary drugs against generalized tonic-clonic seizures, i.e., carbamazepine, phenytoin, phenobarbital, primidone and valproate, had indices of more than 5 in the MES threshold model, while drugs with efficacy against absence and myoclonic seizures, i.e., valproate, ethosuximide and the benzodiazepines, had protective indices of at least 5 in the i.v. PTZ seizure threshold model. The data substantiate that valuable information can be obtained by estimation of protective indices. However, in order to minimize the possibility that an interesting new anticonvulsant compound is overlooked during primary or secondary screening, a protective index of 2 should be considered sufficient in case of traditional MES or s.c. PTZ models with fixed seizure stimulus. Alternatively, seizure threshold models could be used for calculation of protective indices in order to avoid underestimation of anticonvulsant selectivity of test compounds. PMID- 1884715 TI - Intraperitoneal phenytoin suppresses kindled responses: effects on motor and electrographic seizures. AB - Controversy has arisen about the effectiveness of phenytoin against kindled seizures. It has been suggested that the reports of ineffectiveness could be accounted for by phenytoin being given by an intraperitoneal (i.p.) route in those experiments so that adequate serum concentrations were not achieved. Another possibility for the different results was dissimilar stimulus protocols employed in the various studies. The present study examined these issues. Doses of i.p. phenytoin were studied for their actions against kindled responses elicited with short (1 s) and long (10 s) stimulus trains through hippocampal electrodes. Serial application of the stimuli determined time-action relationships. Dose-dependent effects were demonstrated for all time points examined. There was a consistently greater suppression of kindled motor seizures than limbic behavioral seizures or electrographic seizures. Phenytoin either totally blocked or did not affect the duration of afterdischarges. Actions of phenytoin against responses by short duration stimuli were greater than against long duration stimuli. Additional pharmacokinetic studies compared i.p. versus intravenous (i.v.) phenytoin. After i.p. phenytoin, serum levels peaked later than after i.v. delivery, but were maintained in the 'therapeutic' range longer. The present experiments provide additional support for the idea that kindled seizures are a useful model for complex partial seizures in humans. In addition, they show that major actions of phenytoin are to decrease seizure spread and to elevate afterdischarge thresholds and that the i.p. route is appropriate for assaying the effect of phenytoin against kindled seizures in rats. PMID- 1884716 TI - Seizures can be triggered by stimulating non-cortical structures in the quaking mutant mouse. AB - Mutant Quaking mice (C57BL/6J) display convulsive tonic-clonic seizures that can be either spontaneous or triggered by manipulation of the animal or by auditory stimulation. Several abnormalities have been found (especially in the noradrenergic system) in the brainstem of this mutant strain. We first verified by electrophysiological recording that the cerebral cortex was not involved in the generation or in the development of these fits. Then we showed that tonic clonic seizures similar to those obtained in the freely moving animal were triggered by low-threshold (LT, 5-50 microA) or high-threshold (HT, 55-150 microA) stimuli performed during head restraint. LT stimuli were mostly efficient in a number of ponto-bulbar and mesencephalic structures, including several reticular nuclei, the locus coeruleus, the nucleus subcoeruleus and the red nucleus, whereas HT stimuli were generally necessary to trigger fits by stimulating the nuclei pontis, the substantia nigra, the central gray area and the cerebellar nuclei. Seizures were also provoked at the diencephalic level with LT stimulation delivered in the medial thalamic area, the nucleus reticularis thalami and some subthalamic regions (zona incerta, H field of Forel). In contrast, no fits were obtained by stimulating the cerebellar cortex and the inferior colliculus, the ventral and lateral groups of thalamic nuclei or the telencephalic regions (hippocampus, amygdala, caudate nucleus, putamen and cerebral cortex), with the exception of the globus pallidus. PMID- 1884717 TI - Cerebral activation during speech discrimination in temporal lobe epilepsy. AB - Eight patients with uncontrolled complex partial seizures underwent positron emission tomography with 18-fluoro-2-deoxyglucose both at rest and during an auditory order discrimination task using speech syllables. Eight age-matched controls were scanned under identical conditions; an additional 18 normal subjects were scanned only at rest. No consistent task-related changes were seen in control subjects. For the 3 patients with left temporal epileptogenic foci, left inferior temporal lobe hypometabolism was more evident during the activated than during the resting scan. Activation procedures may augment the diagnostic yield of metabolic scanning in epilepsy. PMID- 1884718 TI - 5-Hydroxytryptamine and its role in migraine. AB - Platelet 5-hydroxytryptamine (5-HT) is diminished during migraine headache and the injection of reserpine, which releases 5-HT from body stores, induces a typical headache in migrainous subjects. The intravenous injection of 5-HT relieves established migraine headache, but causes side-effects of nausea, faintness, paraesthesia and dyspnoea. The 5-HT1-like agonist sumatriptan exerts the beneficial effects of 5-HT with minimal side-effects. Receptors for 5-HT are present in cranial arteries and are also widely distributed in the central nervous system, where they play a role in the neural control of the cranial circulation and endogenous pain control system. The pathophysiology of migraine involves interaction between these central pathways and cranial blood vessels. It is probable that many prophylactic agents exert their action by central 5-HT2 antagonism, whereas termination of an established attack of migraine depends upon constriction of cranial vessels mediated by 5-HT1 receptors. PMID- 1884721 TI - Long-term amiodarone therapy raises serum cholesterol. AB - Serum total cholesterol and triglyceride levels were measured in 12 patients before and 3.6 and 9 months after treatment with amiodarone. In addition, we monitored serum T4, T3, reverse T3 and TSH levels. Amiodarone and its desethyl metabolite levels were measured on each occasion. Serum total cholesterol and T4 levels rose from 5.95 mmol/l, and 102.7 mmol/l respectively at baseline to 6.95 and 115.8 at 6 months and reverse T3 increased at 3, 6 and 9 months from baseline. Serum triglycerides did not change. No relationship existed between cholesterol, T4 and T3 and amiodarone (or its metabolite) levels nor between cholesterol and thyroid hormone levels. These data demonstrate that amiodarone therapy is associated with an elevation in serum cholesterol. This may have clinical implications in view of the current widespread use of the drug. PMID- 1884722 TI - Disposition of epirubicin and metabolites with repeated courses to cancer patients. AB - Thirteen cancer patients were studied following a total of 41 courses of epirubicin (EPI) (38-50 mg.m-2, mean 49.2 mg.m-2, administered by a 60 min infusion), together with other cancer chemotherapeutic agents. The aim was to consider the disposition of EPI and metabolites following subsequent courses as it has been reported that doxorubicin (the 4'-epimer parent of EPI) clearance is increased following the first administration. We have observed that EPI glucuronide accounted for a mean 78.0%, epirubicinol 0.2% and epirubicinol glucuronide 19.3% and that parent EPI accounted for only 2.4% of the EPI compounds measured (mean of all patients and courses) for the 3 h period immediately following the infusion. These data confirm the rapid metabolism of EPI and the dominance of the glucuronidation metabolite pathway (which is not available to doxorubicin) and are compared with the metabolite profile observed in other reports. Large inter- and intra-individual variability in area under the plasma concentration/time curve were observed with no clear evidence of any consistent directional trend for such fluctuations, suggesting that factors contributing to EPI disposition are multivariate. PMID- 1884720 TI - Effects of diltiazem and metoprolol on blood pressure, adverse symptoms and general well-being. The Swedish Diltiazem-Metoprolol Multi-Centre Study Group. AB - General well-being, adverse effects and anti-hypertensive efficacy have been investigated in a double blind, parallel-group, dose-response multicentre study of diltiazem and metoprolol monotherapy for hypertension. 128 patients with primary hypertension were included from 10 participating centres. The patients were randomized to receive oral diltiazem 120-240-360 mg/day or metoprolol 50-100 200 mg/day. Each dose was given for a 4-week period as a forced titration regime. In all 119 patients, 59 and 60, respectively, on diltiazem and metoprolol completed the study protocol. There were dose-dependent reductions in supine and standing blood pressures (BP) after both diltiazem and metoprolol therapy. In the diltiazem group, supine BP was reduced by 10 (11)/10 (6) mmHg (SBP/DBP) at the highest dose level, and the corresponding values for the metoprolol group were 7 (16)/8 (9) mmHg (SBP/DBP). Target pressures (DBP less than or equal to 90 mmHg and/or a reduction in DBP of greater than or equal to 10%) were reached in 63% and 48% of the patients, respectively. The incidence and severity of dose dependent adverse effects, as evaluated by spontaneous reports or open and direct questioning, did not differ between treatments. Subjective well-being, evaluated by a self-administered questionnaire, the MSE-profile, did not differ significantly between diltiazem and metoprolol therapy. However, after an initial slight deterioration, contentment and vitality tended to improve with increasing doses of diltiazem, while a dose-related deterioration in these variables was observed on metoprolol therapy. At the highest dose levels, contentment and vitality tended to be better in the diltiazem than the metoprolol group. Thus, diltiazem and metoprolol in daily doses of 120-360 mg and 50-200 mg, respectively, produce comparable and parallel reductions in supine and standing BP. However, while subjective well-being tended to improve with increasing doses of diltiazem, there was a negative trend for metoprolol. It is concluded that diltiazem, given as monotherapy to hypertensive patients, does not impair subjective well-being. PMID- 1884719 TI - The effects of drugs on tests of thyroid function. AB - Many drugs affect tests of thyroid function through alterations in the synthesis, transport and metabolism of thyroid hormones, as well as via influences on thyrotrophin (TSH) synthesis and secretion. Despite effects on circulating thyroid hormone and TSH levels, few drugs result in important changes in clinical thyroid state, but difficulty in interpretation of thyroid function tests often results. Commonly prescribed drugs including anti-convulsants, non-steroidal anti inflammatory drugs, beta-adrenoceptor antagonists, steroid hormones and heparin may result in abnormal thyroid function tests in the absence of clinical features of thyroid dysfunction. In contrast, lithium and iodine containing drugs, including radiographic contrast agents and amiodarone, may result rarely in overt thyroid disease. PMID- 1884723 TI - Evaluation of a prescription based record-linkage model for epidemiological studies of long-term adverse effects of drugs--with special regard to combined oral contraceptives. AB - The Department of Drugs of the Swedish National Board of Health and Welfare undertook a study of the possibilities of a new scheme for post-marketing surveillance by means of prescription and register based epidemiological studies, primarily of combined oral contraceptives (COC). Based on available data on COC usage patterns and incidence rates of the disease at study, it was estimated that study periods, including the necessary time periods for disease development and generation of a sufficient number of cases, would amount to at least 1 to 13 years for cardiovascular outcomes and 8 to 17 years for reproductive cancers. Prospective and unbiased exposure ascertainment would be the most important advantage. However, delay in follow up, the need for extensive individual questionnaire probing and fear of violation of personal integrity could adversely affect the feasibility of the scheme. Chiefly on the grounds of the extended study periods and magnitude of the necessary infrastructure, it was not judged cost-effective to pursue such a scheme for COC exposure only. It was, however, suggested that it would be considered for epidemiological surveillance of other drugs that are commonly used and for which short term and frequent serious side effects are expected, as for instance lipid lowering compounds, beta-blockers, bensodiazepines and other psychotropic drugs. PMID- 1884724 TI - On the differences in psychotropic drug use between the three major urban areas in Sweden. AB - Marked differences in the utilisation of psychotropic drugs between the three major urban areas in Sweden were recorded from four sources of information: drug supplies from wholesalers to pharmacies, drug supplies to hospitals for in patient use, drugs sold on prescription for out-patient use, and out-patient consultation and drug prescribing as recorded by physicians. The total sales of psychotropics in the counties of Gothenburg (110.8 defined daily doses per 1000 inhabitants per day) and Malmo (102.1) were much higher than in the county of Stockholm (73.4), with about 25% of the difference being accounted for by diazepam. Differences in the total sales of psychotropics were not explained by any differences in hospital sales, which amounted to about 10% in all counties. Prescription sales differed due to the higher average number of DDD (defined daily doses) per prescription in Gothenburg and Malmo than in Stockholm (total psychotropics 8 and 15%, respectively), and especially because of the higher number of prescriptions per inhabitant (about 40 and 30-35%, respectively). There was no substantial difference in the pattern of diagnoses between areas, but there was a noticeable difference with regard to prescriber category, as psychiatrists accounted for more of the prescriptions in Stockholm than in Gothenburg and Malmo. The results raise questions about over- and under-treatment of mental disorders and about abuse of drugs. In order to explain the geographical differences in psychotropic drug sales morbidity patterns and prescribing practices should be further explored. PMID- 1884725 TI - Evaluation of the antianginal effect of nifedipine: influence of formulation dependent pharmacokinetics. AB - Nifedipine capsules t.d.s. and an extended release formulation of nifedipine, nifedipine-ER tablets, given once daily in corresponding daily doses, have been compared with placebo in a double-blind, three-way cross-over study in 24 patients with stable angina pectoris. The objective was to study the influence on the antianginal effect of the different pharmacokinetics of several preparations of nifedipine. All patients received concomitant treatment with beta-adrenoceptor blockers. Antianginal efficacy was assessed by a dynamic exercise test at the end of the dosage intervals, i.e. 8 and 24 h after nifedipine capsules and nifedipine ER, respectively, as well as 6 h after dosing. Six h after dosing the time of onset of chest pain and total exercise time were longer and total work was significantly higher during both nifedipine-ER (plasma concentration 260 nmol/l) and placebo treatment than after nifedipine capsules (plasma concentration 78 nmol/l). Time to 1 mm ST depression was longer during nifedipine-ER than during nifedipine capsule treatment. No significant difference was seen between nifedipine-ER and placebo. At the end of the dosage interval (24 and 8 h after nifedipine-ER and nifedipine capsules, respectively), no significant difference was found between nifedipine-ER (plasma concentration 75 nmol/l) and the other two treatments. However, placebo was superior to nifedipine capsules (plasma concentration 58 nmol/l) both in the time to onset of chest pain and total exercise time. The lack of effect at the end of the dosage interval was probably due to the subtherapeutic plasma nifedipine level.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1884726 TI - Improved bioavailability from a spironolactone beta-cyclodextrin complex. AB - The relative bioavailabilty of spironolactone from a complex with beta cyclodextrin has been evaluated. Capsules containing 100 mg micronised spironolactone powder were compared with 100 mg spironolactone beta-cyclodextrin complex in 8 healthy volunteers by a single dose, double blind, crossover pharmacokinetic study. Subjects were randomly allocated to each preparation and crossed over after 2 weeks. Relative bioavailability was assessed by the measurement of serum canrenone concentrations. The mean relative bioavailability of the spironolactone cyclodextrin complex, compared to the micronised spironolactone powder, was 233%. Statistical analysis (Wilcoxon signed rank test) revealed that this difference was significant with a mean area under the serum concentration time curve of 3.90 and 1.88 mg.h.l-1 for the complex and micronised spironolactone powder, respectively. Four of the volunteer also received a 100 mg spironolactone tablet (Aldactone) under identical conditions. Pharmacokinetic analysis revealed that the mean relative bioavailability of the spironolactone beta cyclodextrin complex and micronised powder when compared with spironolactone tablets (Aldactone) was 252% and 124%, respectively. There was no change in the canrenone elimination half lives of each subject. PMID- 1884727 TI - Cyclosporine pharmacokinetics in liver transplant recipients: evaluation of results using both polyclonal radioimmunoassay and liquid chromatographic analysis. AB - Pharmacokinetic variables were derived from cyclosporine measurements using liquid chromatography (HPLC) and radioimmunoassay with a non-selective polyclonal antibody (PARIA) in 11 orthotopic liver transplant recipients studied in paired oral and intravenous studies both before and after permanent clamping of the biliary T-tube. After oral drug administration, mean areas under blood cyclosporine concentration versus time curves before clamping were around 5.2 fold greater by PARIA than HPLC but 2.9-fold greater after clamping and closer to comparable values after intravenous cyclosporine (2.5 and 2.3-fold, respectively). Cyclosporine clearance was smaller by PARIA than HPLC (mean 7.3 versus 3.3 ml.min-1.kg-1, respectively, before clamping). Both values decreased by 25% after clamping (to 5.5 and 2.4 ml.min-1.kg-1, respectively), although there was no significant change in distribution or elimination half-lives (around 0.5 and 8 h, respectively). The mean bioavailability of oral cyclosporine increased significantly after clamping in 9 patients (from 10.6% to 28.1% by HPLC and from 14.8 to 35.1% by PARIA) but in two patients who developed the vanishing bile duct syndrome values fell to less than 10% and the proportional overestimation of cyclosporine concentrations by PARIA increased. Clamping had no singificant effect on the mean apparent volumes of distribution but values of Vz were approximately twice those of Vss (around 2.6 and 1.31.kg-1 by PARIA and HPLC respectively). Mean half lives after clamping were shorter following oral than intravenous cyclosporine (t 1/2 lambda 2 around 15 h enterally versus 8 h parenterally).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1884728 TI - Pharmacokinetics and metabolism of cyclophosphamide administered after total body irradiation of bone marrow transplant recipients. AB - High-dose cyclophosphamide is used immediately after total body irradiation (TBI) in conditioning for bone marrow transplantation (BMT). Possible interactions of the two treatment modalities were sought by measuring the blood pharmacokinetics of CP and 4-hydroxy-cyclophosphamide (4-HOCP) in patients undergoing BMT. There was a non-significant trend to a shorter half-life of CP compared to reported values. Exposure to 4-HOCP, the major metabolite of CP, did not appear to be altered by prior TBI of the patient. PMID- 1884729 TI - Oxidative polymorphism of debrisoquine is not related to human colo-rectal cancer. AB - The oxidative polymorphism of debrisoquine (DBQ) has been determined in 89 patients with colo-rectal cancer and in 556 normal control subjects. Four patients and 34 controls, with a metabolic ratio greater than 12.6, were classified as poor metabolisers of DBQ (n.s.). No difference was found in the distribution of the frequencies of the MR of DBQ between patients and controls. It is concluded that polymorphic oxidation of DBQ is not related to the risk of developing colo-rectal cancer in human beings. PMID- 1884731 TI - The central haemodynamic effects of a single intravenous dose of flosequinan in patients with severe heart failure. AB - The acute central haemodynamic and neuroendocrine effects of intravenous flosequinan were studied in a group of 10 patients with severe heart failure. Flosequinan improved cardiac output by a maximum of 1.59 l.min-1, it reduced pulmonary capillary wedge pressure by 11.9 mm Hg and it also caused a reduction in right atrial pressure by a maximum of 7.2 mm Hg. It tended to cause a fall in plasma adrenaline levels but not in plasma noradrenaline. There was little fall in blood pressure in response to flosequinan and no patient developed an adverse event. Intravenous flosequinan may be a useful candidate drug for controlled clinical studies in patients with severe heart failure. PMID- 1884730 TI - Debrisoquine oxidation polymorphism in a Tasmanian population. AB - The debrisoquine hydroxylation phenotype was studied in 152 unselected healthy Tasmanian subjects, who were mostly Caucasians of British ancestry. Following a 10 mg oral dose of debrisoquine (D), the ratio of D/4-hydroxydebrisoquine excreted in 8-h urine (metabolic ratio, MR) was determined. MR values were bimodally distributed. Thirteen subjects (8.6%) had MR values from 13.8 to 93.3 and were considered to be poor metabolisers of D, while the others were extensive metabolisers with MR values of 0.04 to 5.4. The D hydroxylation phenotype was not associated with sex. These findings confirm the constancy of D polymorphism in a Caucasian population even after migration to another country. PMID- 1884732 TI - Comparison of postpartum pain treatments using a sequential trial design: II. Naproxen versus paracetamol. AB - The efficacy of naproxen and paracetamol in relieving uterine cramps has been compared in a sequential trial. The treatments did not differ significantly in a two-sided test in 56 patients. A corresponding fixed sample test would have required 140 patients to obtain the same significance level and power. In addition to uterine pain, the effect on episiotomy pain was also estimated at the termination of the trial. Again, there seemed to be no difference between naproxen and paracetamol. PMID- 1884733 TI - Comparative study of the efficacy of dipyrone, diclofenac sodium and pethidine in acute renal colic. Collaborative Group of the Spanish Society of Clinical Pharmacology. AB - A randomized, double-blind, multicentre clinical trial was designed to compared the analgesic efficacy of i.m. dipyrone 1 and 2 g, i.m. diclofenac sodium and i.m. pethidine in acute renal colic. The study was carried out in 451 patients in 13 Spanish hospitals. Ureteric colic was diagnosed by the clinical features, urinalysis, or when the presence of a ureteric calculus was confirmed. The severity of pain was assessed by the physicians and by patients using visual analogue scales. The main parameter of drug efficacy was the need for rescue treatment-pethidine 100 mg i.m. 30 min after the experimental treatment. Rescue treatment was required in 93 patients: they represented 24.1% of the group given dipyrone 1 g; 22.3% of those on dipyrone 2 g; 16.4% of those given diclofenac sodium; and 19.5% of those on pethidine. The differences between the groups were not significant. In the remaining 358 patients, no difference between treatments was observed. The results suggest that in acute renal colic the use of dipyrone 2 g is unjustified as dipyrone 1 g is equally effective. Diclofenac sodium is a valid alternative, which shows similar analgesic efficacy. PMID- 1884734 TI - Metabolism of paracetamol and phenacetin in relation to debrisoquine oxidation phenotype. AB - The metabolism of paracetamol and phenacetin has been studied in subjects previously phenotyped as either extensive or poor metabolisers of debrisoquine (EM and PM, respectively), in order to examine the relationship between phenacetin and paracetamol activation and debrisoquine oxidation status. In separate experiments, paracetamol and phenacetin were administered orally to groups of 5 EM and 5 PM subjects, and the excretion of metabolites measured for 24 h. There were no differences between EM and PM subjects in the excretion of metabolites. After phenacetin, 0.82 of the dose was recovered in urine, mostly as paracetamol glucuronide (51%) and sulphate (30%), with smaller amounts of free paracetamol (4%) and the mercapturate (5%) and cysteine conjugates (5%), 2 hydroxyphenetidine (5%) and N-hydroxyphenacetin (0.5%). Following paracetamol, 0.87 of the dose was recovered, with similar proportions of paracetamol-derived metabolites. It is concluded that the debrisoquine oxidation phenotype is unrelated to either the metabolic activation of phenacetin and paracetamol, or to their overall metabolic clearance. PMID- 1884736 TI - Prescription of drugs not listed in a clinic's pharmacopoeia: supervision by clinical pharmacologists. AB - The pharmaceutical market in the FRG offers about 11,000 different preparations and formulations. A restricted list (pharmacopoeia) containing approximately 1,000 drugs has been proved to cover the routine requirements of a university clinic and most of the additional drugs demanded by the physicians as 'exceptis excipiendis'. Restrictive control of requests for drugs not included in the internal pharmacopoeia by clinical pharmacologists has reduced the absolute number of requests by half, and about 60% of the remaining requests could be replaced by drugs listed in the pharmacopoeia. The majority of the special requests arose from the continuation of drugs presented to out-patients by the resident physicians after admission of the patient to the hospital. The supervision may lead to more critical revision of out-patient medication, but a substantial reduction of drug expenditure was not attained, as the drugs requested amounted only to a minor fraction of the overall drug expenditure by the hospital. PMID- 1884735 TI - Omeprazole in elderly duodenal ulcer patients: relationship between reduction in gastric acid secretion and fasting plasma gastrin. AB - The effect of omeprazole on acid secretion and gastrin levels has been investigated in 10 elderly duodenal ulcer patients in remission. Doses of 5, 10, 20 and 40 mg omeprazole were given once daily for 7 consecutive days and the basal (BAO) and peak (PAO) acid output and fasting plasma gastrin concentration were measured 24 h after the seventh dose. Omeprazole suppressed PAO significantly and dose-dependently after doses of 10, 20 and 40 mg, the suppression being 42%, 75% and 85%, respectively. No patient showed complete inhibition of PAO and at least 20 mg had to be given to obtain a marked inhibitory effect in all patients. Increasing the dose to 40 mg had only a slight additional effect compared to 20 mg. There was a relationship between degree of acid inhibition and the increase in fasting plasma gastrin. PAO had to be suppressed by more than 80% before a moderate increase in fasting plasma gastrin was observed. The optimal once-daily oral dose of omeprazole for inhibition of acid secretion in elderly patients appears to be 20 mg. Omeprazole 20-40 mg may cause a moderate increase in fasting plasma gastrin. PMID- 1884737 TI - Monitoring of the free concentration of cyclosporine in plasma in man. AB - The free fraction of cyclosporine A (CsA) and its total plasma concentration as determined by HPLC(CsAT) were prospectively monitored in 66 recipients of renal transplants. The free CsA levels (CsAu) were calculated. The variability in free CsA levels was no less than for total CsAT levels. The correlation between CsAu and CsAT was high (r = 0.90). Both CsAT and CsAu covaried with serum triglycerides and apolipoprotein A1. Fourty-four of the 66 patients suffered acute rejection episodes on 69 occasions. CsAT and CSAu both decreased and to a similar extent at the occurrence of acute rejection (42% and 59% decrease, respectively; significant vs baseline. Not significant difference in decrease in CsAT vs CsAu). Acute nephrotoxicity occurred on 11 occasions in 10 patients. Both CsAT and CSAu were approximately twice as high at the time of acute nephrotoxicity as compared to one week previously. Both CsAT and CsAu were higher during the first month after transplantation in patients with than in patients without systemic infection. Thus, plasma CsAu gave no additional clinical information or guidance compared to CsAT in renal transplant recipients. Due to the complexity of its assay, which requires two consecutive analyses, there does not appear to be any need for routine monitoring of CsAu in renal transplant recipients. PMID- 1884738 TI - Inhibition of human erythrocyte and gastroduodenal catechol-O-methyltransferase activity by nitecapone. AB - The effect of increasing single oral doses of the novel catechol-O methyltransferase (COMT) inhibitor, nitecapone, on enzyme activity in red cells (RBC) and gastroduodenal COMT activity has been studied in healthy male volunteers. A dose-dependent decrease in RBC COMT activity was seen in all cases after 1 to 150 mg of the drug. The highest dose of 300 mg did not produce much more inhibition of COMT than 150 mg. The inhibition was not complete; at the highest doses the COMT activity was reduced by 50-60%. The effect and the duration of the inhibition in RBC COMT was strongly correlated with plasma nitecapone concentrations in the dose range up to 150 mg. RBC COMT activity recovered fully in 4 h after medication. Gastric mucosal COMT activity was several-fold higher than that in RBCs. It was also dose-dependently inhibited at the two doses (25 and 100 mg) studied. The inhibition of gastric and duodenal COMT was greater than that in RBCs. This also indicates that nitecapone is locally active in the gastroduodenal tract. The results confirm nitecapone as a potent COMT inhibitor in human tissues. New COMT inhibitors may provide a valuable approach to the treatment of Parkinson's disease in combination with L dopa and dopa decarboxylase inhibitor therapy. PMID- 1884739 TI - The measurement of ofloxacin in hair as an index of exposure. AB - Several strands of hair were collected from each of patients who had been taking ofloxacin against bacterial infections some time in the past. In 10 out of total 14 subjects studied the drug was detected only in the hair portions corresponding to the administration period with the assumption of the hair growth rate of about 1 cm/month. Even in a subject who had received 300 mg/day of ofloxacin only for two days the drug could be detected in the corresponding portion. In 3 subjects the drug was detected in some other portion(s) than the corresponding ones. This might be due to the uncertainty of having used the drug on the other occasion. Only in one subject the dosage history could not be deduced from the drug distribution along hair length. In 3 subjects, who had taken the drug within 1 month, hair samples were collected every month for 3 or 4 consecutive months. The front of drug appearance in hair was clearly shown to move outwards along hair shaft every month at a pace of 1-1.5 cm/month. These results suggest that ofloxacin is excreted into human scalp hair, captured there and moves outwards along the hair shaft at its own growth rate. This leads to the concept that the distribution of ofloxacin along hair length can be used for knowing the individual exposure or non-exposure to the drug, and even for knowing hair growth rate when the innoculation(s) of the drug is strictly supervised and recorded. PMID- 1884740 TI - Dopamine pharmacokinetics in critically ill newborn infants. AB - Dopamine is frequently used in critically ill newborn infants for treatment of shock and cardiac failure, but its pharmacokinetics has not been evaluated using a specific analytical method. Steady-state arterial plasma concentrations of dopamine were measured in 11 seriously ill infants receiving dopamine infusion, 5 20 micrograms.kg-1.min-1, for presumed or proven sepsis and hypotensive shock. Steady-state concentrations of dopamine ranged from 0.013-0.3 microgram/ml. Total body clearance averaged 115 ml.kg-1.min-1. The apparent volume of distribution and elimination half life averaged 1.8 l.kg-1 and 6.9 min, respectively. No relationship was observed between dopamine pharmacokinetics and gestational age, postnatal age or birthweight. Substantial interindividual variation was seen in dopamine pharmacokinetics in seriously ill infants, and plasma concentrations could not be predicted accurately from its infusion rate. Marked variation in clearance explains in part, the wide dose requirements of dopamine needed to elicit clinical response in critically ill newborn infants. PMID- 1884741 TI - Intraindividual variation in 6-mercaptopurine pharmacokinetics during oral maintenance therapy of children with acute lymphoblastic leukaemia. AB - Intraindividual variation in 6-mercaptopurine (6-MP) kinetics has been little studied. It has now been examined in 18 children with acute lymphoblastic leukaemia (ALL). On 2 to 4 occasions in each patient drug concentrations in plasma and red cells were followed for 4 h after administration by means of HPLC. The mean individual coefficient of variation (C.V.) in AUC was 57.9% and it was not related to dose or concentration. The variation was the same in plasma and in red cells. It is concluded that regular monitoring of 6-mercaptopurine concentration would identify periods when a patient deviates strongly from the mean range. Both undertreatment and concentration-dependent toxicity could then be corrected. PMID- 1884742 TI - Interspecies differences in the effect of pH on gallopamil protein binding to albumin and alpha 1-acid glycoprotein. AB - There is little information about the factors which influence drug protein binding between species. We have therefore investigated the role of pH on the binding of gallopamil, a calcium channel antagonist known to exhibit pH-sensitive binding, among four species, human, baboon, bovine, and canine. We used pure protein solutions of alpha 1 acid glycoprotein (AAG) (60 mg.l-1), albumin (45 gm.l-1), and their combination and three values of pH, 7.0, 7.4, and 8.0. Gallopamil protein binding was determined over a concentration range of 2.0 x 10( 7) mol.l-1 to 2.1 x 10(-3) mol.l-1 using equilibrium dialysis. Gallopamil binding in all solutions was best described using a two binding site model in the combination solution and a one binding site model in the pure solutions. pH did not affect the number of identical binding sites. However, the influence of pH on gallopamil binding was species specific. Increasing the pH from 7.0 to 8.0 influenced binding affinity differently between species. There were directionally similar changes in unbound fraction at a gallopamil concentration of 2 x 10(-7) mol.l-1 as pH increased, although there were species differences in the degree of change. In protein solutions containing both AAG and albumin a reduction in pH from 7.4 to 7.0 resulted in species-specific increases in the unbound fraction. Increasing the pH from 7.4 to 8.0 again resulted in species-specific reductions in the unbound fraction of gallopamil. Similar changes were seen when pure AAG or albumin solutions were used, indicating species variance in both gallopamil protein binding and the effect of pH on binding. PMID- 1884743 TI - S-mephenytoin 4-hydroxylation in older Americans. AB - To examine whether a drug-metabolizing enzyme changes with normal aging, the S:R index of S-mephenytoin 4-hydroxylation was determined in 150, unmedicated elderly Americans (mean age 75.4). Ten (6.7%) were identified as categorically slow metabolizers (S:R ratios greater than or equal to .95). This increased incidence of slow metabolizers was accounted for by a significant and previously unreported, increased proportion of slow metabolizers among the black (18.5%) as compared to the white subjects (4.1%) (P = .017). There was no relationship found between S:R ratios and age or creatinine clearance. PMID- 1884744 TI - Haemodialysis studies with dichloroacetate. AB - Seven patients undergoing routine thrice weekly haemodialysis for endstage renal failure participated in 12 investigations of dichloroacetate (DCA) pharmacokinetics and pharmacodynamics. DCA doses were 50 mg/kg by i.v. infusion over 30 min. In each investigation single doses were administered to each subject on two consecutive days, one being a day during which the patient was dialyzed. The timing of drug administration, relative to dialysis, was varied to assess the effect of dialysis on the apparent volume of distribution and elimination rate constants of DCA and on its effect on blood glucose and lactate. Dialysis increased the clearance of DCA by approximately 60%, but had no effect on its apparent volume of distribution. Dialysis did not reduce the maximal lactate lowering effect of DCA, but slightly decreased the duration of this effect. Blood glucose levels were not significantly altered by DCA and no adverse drug effects were observed. We conclude that dialysis increases plasma clearance of DCA, but has little influence on the metabolic effects of the drug when given at 50 mg/kg doses. DCA can safely and effectively be given to hemodialysis patients who may require the drug for treatment of lactic acidosis. PMID- 1884745 TI - The concentration-dependent disposition and kinetics of inulin. AB - The disposition of inulin was studied in 30 healthy male and 10 healthy female volunteers, and 10 patients with stable chronic renal failure (mean creatinine clearance 45 ml.min-1) following intravenous infusion of 70 mg.kg-1 over 5 min. Plasma concentrations fell rapidly initially but the rate of decline decreased continuously over 8 h and a linear terminal elimination phase could not be identified. Inulin was excreted rapidly by the subjects with normal renal function and 97.3% of the dose was recovered in the urine in 8 h. There was a progressive highly significant fall in the renal clearance of inulin after 2 h as plasma concentrations fell below about 150 mg.l-1. Six to 8 h after administration the clearance was less than 50% of the initial value in the healthy volunteers and the corresponding fall in the renal patients was 33%. The concentration-dependent renal clearance of inulin was confirmed in "step-up" and "step-down" constant infusion studies in which clearances were measured at mean plasma concentrations ranging from 35.2 to 186.7 mg.l-1. These studies virtually excluded time, changes in posture and urine flow rate as important factors. There was no statistically significant fall in clearance during the first 2 h and kinetic analysis was based on data obtained over this time.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1884746 TI - Time course of the anti-oedematous effect of O-(beta-hydroxyethyl)-rutosides in healthy volunteers. AB - O-(beta-hydroxyethyl)-rutosides (HR) is used for the treatment of disorders of the venous and microcirculatory systems. In order to evaluate the time course of its activity, the effect of HR on a provocation model of orthostatic oedema in healthy volunteers was used. After a 2 week placebo run-in period, 16 healthy volunteers were randomized to HR (2 tablets of 500 mg/day) of placebo for a further 3 weeks, in a double-blind parallel design. Oedema was provoked by standing motionless for 1 h, with measurement of leg volume before and afterwards. The procedure was undertaken at entry to the study and then weekly during the entire 5 week period. There were no significant differences in the extent of oedema produced by the orthostatic challenge during the 2 week run-in period or in the subjects who continued on placebo (approximately 90 arbitrary units i.e. approximately 48 ml). During the 3 week treatment with HR, however, there was a progressive reduction (-1.1, -5.9, and -7.6 arbitrary units after 1, 2, and 3 weeks, respectively) in the volume of induced oedema, which was significant after 2 and 3 weeks of treatment compared to the placebo group. PMID- 1884747 TI - Comparison of the bioavailability of two slow release preparations of disopyramide. AB - The bioavailability of two slow release preparations of disopyramide has been compared in a randomized cross-over trial of Rythmodan L.A. 250 mg b.d. and Dirytmin Durettes 300 mg b.d., given to 10 healthy volunteers. The plasma concentrations of disopyramide were measured on the 5th day of each treatment period. With both preparations, plasma concentrations were well sustained. The amount absorbed was slightly lower after Rythmodan L.A. than after Dirytmin Durettes, but the fluctuations over a dosing interval were significantly more pronounced for Dirytmin Durettes than for Rythmodan L.A. PMID- 1884748 TI - Effect of ampicillin on mefloquine pharmacokinetics in Thai males. AB - The kinetics of a single oral dose of mefloquine given either alone or with ampicillin has been studied in 8 healthy Thai male volunteers. There was a significantly higher maximum whole blood mefloquine concentration after coadministration with ampicillin (1648 vs 1228 ng.ml-1), as well as a significantly reduced terminal half life (15.3 vs 17.7 days), mean residence time (20.1 vs 23.4 days) and volume of distribution at steady state (14.1 vs 19.4 l.kg 1). Although there was no significant change in the AUC from zero time to infinity, the AUC from zero time to 5 days was significantly increased by ampicillin (4.86 vs 3.27 micrograms.ml-1 day). These changes in mefloquine disposition after antibiotic treatment may be due both to an increase in fractional bioavailability and a reduction in the enterohepatic recycling of mefloquine. PMID- 1884749 TI - Heroin intoxication: the relation between plasma morphine concentration and clinical state at admission. PMID- 1884751 TI - Differential effects of (-)-baclofen on Ia and descending monosynaptic EPSPs. AB - 1. In cats anesthetized with alpha-chloralose, population synaptic responses of motoneurons produced by stimulation of group I afferents were recorded from ventral roots with a sucrose gap or extracellularly from the motor pool. These responses were depressed, and often abolished, following the intravenous injection of 1-3 mg/kg of (-)-baclofen, a presumed GABAb agonist. 2. The monosynaptic population responses of motoneurons produced by stimulation of the ipsilateral ventromedial funiculus (VMF), the bulbar reticular formation or the vestibular nucleus, were also depressed following the administration of (-) baclofen, but to a lesser degree than responses produced by stimulation of group I fibers. 3. Depression of the synaptic actions of Ia and of descending fibers following the administration of (-)-baclofen occurred without significant changes in the presynaptic volley recorded from the cord dorsum. However, in 3/4 experiments the intraspinally recorded Ia terminal potential was reduced following the injection of (-)-baclofen. The VMF terminal potentials were also depressed, but to a lesser degree. 4. Intracellular recordings from spinal motoneurons indicate that the (-)-baclofen-induced depression of the monosynaptic Ia- and VMF-EPSPs occurred without important changes in the time course of EPSP decay. This suggests that with the amounts used, postsynaptic changes were not contributing significantly to the EPSP depression. 5. It is suggested that (-) baclofen depresses synaptic transmission probably by activation of GABAb receptors located at the intraspinal terminations of Ia and descending fibers. The lower sensitivity of VMF actions to (-)-baclofen would be accounted for by a relatively low density of baclofen receptors in descending fiber terminals. PMID- 1884750 TI - Descending input from the hypothalamic paraventricular nucleus to sympathetic preganglionic neurons in the rat. AB - The descending projection of the hypothalamic paraventricular nucleus (PVN) to the sympathetic preganglionic neurons (SPNs) in the upper thoracic cord of the rat was studied. PVN-fibers were labeled by anterograde transport of Phaseolus vulgaris leucoagglutinin (PHA-L), while SPNs were retrogradely labeled with cholera toxin subunit B (CTb) which was injected into the superior cervical ganglion. SPNs labeled with CTb were mainly observed in the nucleus intermediolateralis (IML) pars principalis and pars funicularis, and a small number of them were in the nucleus intercalatus (IC) and central autonomic nucleus (CA). SPNs found in the IML had dendrites that projected in various directions. Five types of dendritic projections were noted: medial, rostral, caudal, lateral (including dorsolateral) and ventral. Longitudinal dendritic bundles interconnected each cell cluster in the IML. Medial dendrites of the IML, together with dendrites of the IC and CA, formed transverse dendritic bundles extending from the IML to the central canal. The transverse dendritic bundles disentangled near the midline and formed a loose dendritic plexus in the region just dorsal to the central canal. PVN-fibers labeled with PHA-L were observed primarily in lamina I and intermediate gray (lamina VII). Although varicose PVN fibers and SPNs coexisted in the IML, the tight packing of the dendritic bundles prevented any clear demonstration of direct contacts between them. On the other hand, PVN-fibers were occasionally found to appose and wind around the primary or secondary dendrites of some SPNs of the CA and IC. These dendrites were studied with varicosities of PVN-fibers for a short length, and terminal boutons of PVN fibers were also seen to make contact directly with the dendrities. The results of this study substantiated a direct connection between the PVN and SPNs, using a combination of immunohistochemical techniques for PHA-L and CTb. The possible involvement of a direct pathway from the PVN to SPNs in cardiovascular regulation is discussed. PMID- 1884752 TI - Number of GABA-immunopositive and GABA-immunonegative neurons in various types of neocortical transplants. AB - Quantitative investigation of GABA-immunopositive and GABA-immunonegative neurons was performed in grafts of embryonic tissue of somatosensory cortex, (1) injected intraparenchymally into the barrel field of adult rats (n = 5); (2) placed in an acute cavity in the same area (n = 9); or (3) implanted into the anterior eye chamber (n = 5). Analysis of initial embryonic tissue at the age of grafting (E17) demonstrated high numerical density of neurons both GABA-positive and other. Six months after grafting the total neuronal density was higher than in normal cortex in both groups of intracortical grafts, but was lower than normal in the intraocular grafts. The numerical density of GABA-positive somata, however, decreased in all types of the grafts, and their ratio to GABA-negative neurons was significantly lower than in normal neocortical tissue. The total numerical density of the neurons in the grafts had strong positive correlation to the degree of morphological graft/host integration, which was evaluated as a ratio of extent of area of direct graft/host neuropil confluence versus the total extent of the border. The mean diameters of nuclei of GABA-negative cells in both groups of intracortical grafts did not differ from those of the intact neocortex, but in the isolated grafts they were substantially larger. Nuclei and somata of the GABA-positive cells, however, were hypertrophic in all groups of grafts, and especially in the intraocular ones. Measurements of the diameters of host neocortical neurons adjacent to the grafts also exhibited a less marked but still significant hypertrophy. The possible role of various factors (synaptic, trophic, functional), determining the described alterations in neuronal populations within the grafts is discussed. PMID- 1884754 TI - The perforant path in the seizure sensitive gerbil contains the Ca(2+)-binding protein parvalbumin. AB - The Mongolian gerbil (Meriones unguiculatus) is used as a model in epilepsy studies. Structural abnormalities in the hippocampus and in its GABAergic system have been correlated with this affliction. A reliable marker of a subpopulation of GABAergic neurons is the Ca2+ binding protein parvalbumin (PV). Here we show that, whereas PV is present in the same population of hippocampal interneurons in gerbil as described in the rat, in the gerbil, PV-immunoreactivity is also found in the outer molecular layer of the hippocampus. Ultrastructural analysis revealed that it is located there in axospinous boutons with asymmetric synaptic junctions, i.e. the terminals of the entorhinal perforant path. Upon ablation of the intensely PV-immunoreactive entorhinal cortex, PV-staining is completely absent in its hippocampal termination zones. Thus, in gerbil hippocampus (but not in the rat, mouse, cat and man) PV is contained in a presumably excitatory projection. This outstanding feature of the limbic system of the gerbil implies different functional properties related to Ca2+ mediated processes, and could be of relevance for the seizure sensitivity of this animal species. PMID- 1884753 TI - Calcium-binding proteins are concentrated in the CA2 field of the monkey hippocampus: a possible key to this region's resistance to epileptic damage. AB - Previous immunocytochemical studies have shown a heterogeneous distribution of parvalbumin (PA) and calbindin (CB) in the rat hippocampal formation. The results of the present study showed a heterogeneous distribution of PA and CB in primate Ammon's horn. The density and intensity of immunoreactivity for both of these calcium-binding proteins was greatest in CA2 as compared to CA1 and CA3. CB immunoreactivity was localized to the cell bodies, dendrites, and axon initial segments of pyramidal cells whereas PA-immunostaining was found in the axon terminals, dendrites and cell bodies of interneurons that have features similar to GABAergic inhibitory neurons. Based on previous studies that have shown a protective role of calcium-binding proteins in neurons exposed to hyperstimulation, these results suggest that the resistance of CA2 pyramidal cells in temporal lobe epilepsy is due to the high concentration of CB and PA in this region of Ammon's horn. PMID- 1884755 TI - Control of asymmetrical bimanual movements. AB - When movements are performed together in the upper-limbs, a strong tendency emerges to synchronize the patterns of motor output. This is most apparent when trying to do different things at the same time. The present experiment explored the simultaneous organization and control of spatiotemporally different movements. There were two practice conditions: symmetrical and asymmetrical. In the symmetrical condition, subjects performed a series of unidirectional elbow flexion movements, followed by a series of elbow flexion-extension-flexion (reversal) movements in both limbs simultaneously. In the asymmetrical practice condition, subjects performed the unidirectional movement in the left limb together with the reversal movement in the right limb. Findings revealed a tendency for each limb movement to assimilate the features of its counterpart under the latter condition. This effect was "asymmetrical" in that the unidirectional movement was more attracted to the reversal movement than vice versa. Nevertheless, subjects were able to partly suppress this synchronization tendency as was evident from the moderate cross correlations between the angular acceleration patterns of both limb movements and from an increasingly successful differentiation of the activity levels in the right and left limb muscles. All together, these findings provide evidence for some degree of parallel control of spatiotemporally different actions. The data are discussed in view of the possible suppression of a bilaterally distributed motor control system, that is mainly held responsible for activiting proximal limb musculature. PMID- 1884756 TI - Functional connections in the human temporal lobe. II. Evidence for a loss of functional linkage between contralateral limbic structures. AB - In a previous investigation of functional limbic pathways in the human mesial temporal lobe, we found evidence for strong connections between ipsilateral mesial temporal structures, but none for contralateral functional connections (Wilson et al. 1990). In the present study, we focused specifically upon the question of functional commissural linkages between these structures by systematic stimulation of a total of 390 electrode placements in 74 epileptic patients with temporal lobe depth electrodes implanted for surgical diagnosis. Eight standard electrode placement regions were targeted: amygdala, entorhinal cortex, anterior, middle and posterior hippocampus, subicular cortex, middle parahippocampal gyrus, and posterior parahippocampal gyrus. Three to six electrodes were implanted bilaterally in each patient, and each electrode was individually stimulated while recording from all the other sites. Out of the 390 electrodes stimulated, 78% were effective in evoking clear responses in adjacent ipsilateral structures, and 75% of 581 ipsilateral recording sites were responsive to stimulation. Only one of the stimulated electrode sites was effective in evoking responses in contralateral recording sites, and only two of 511 contralateral recording sites were responsive to that stimulation. The effective stimulation site was in presubicular cortex, and the responsive contralateral recording sites were in entorhinal and presubicular cortices. Response to this stimulation site was intermittent and variable in latency. The relative ease of obtaining functional verification of significant ipsilateral anatomical pathways in the human limbic system, and the sharply contrasting difficulty of functionally activating commissural pathways to contralateral limbic sites are discussed in the context of decreases in hippocampal contribution to commissural pathways in the primate brain compared to sub-primate mammals, and the significance of this change to normal limbic system function as well as to mechanisms of seizure spread in epilepsy. PMID- 1884757 TI - Influence of different properties of a reaction time task on the pre-movement gating of input from Ia afferents to motoneurons. AB - The monosynaptic reflex (H reflex) is facilitated before movement onset in human subjects who are performing a conditioned plantar flexion of the ankle in a reaction time task. The aim of this study was to investigate how tightly this gating of Ia spindle input is coupled with the conditioned muscle contraction. Test H reflexes were elicited at various times during the reaction time (RT) in order to test the efficacy of Ia volleys on the soleus motoneurons. Tactile, auditory and visual go stimuli were used. The RT to a tactile stimulus was about the same as the RT to an auditory stimulus although distance and therefore conduction time from the site of stimulation to the cerebral cortex was much larger for the tactile than for the auditory modality. The RT to visual stimulation was about 20 ms longer than to the other two modalities. Although central latencies depended clearly on the stimulus modality the duration of the H reflex facilitation, i.e. the interval between the onset of the facilitation and the onset of the voluntary muscle contraction, was always the same. Similarly, the reflex facilitation was insensitive to the succeeding contrast of a visual go stimulus. The subjects were also examined in visual RT tasks in which different advance information about the laterality and the execution of the contraction was given. By combination the following four RT situations were realized: (1) simple, go, (2) choice, go, (3) simple, go-no go and (4) choice, go-no go.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1884758 TI - Eye and head coupled and dissociated movements during orientation to a double step visual target displacement. AB - Tight coupling between eye and head movements has been observed in response to a single visual target offset. On this basis, when the visual stimulus consists of two successive steps in the same (horizontal) direction, either increasing in eccentricity (staircase) or decreasing in eccentricity (pulse-step) gaze should be due to concomitant eye and head angular displacement. That is, the eyes and head should aim at each target displacement so that their combined movement matches target offset. We have tested this hypothesis in five healthy subjects. The measured variables were head and gaze offset, the interval between two consecutive saccades from onset to onset (I) and the response delay between onset of the second step and onset of the first gaze saccade (D). With both staircase and pulse-step stimuli, the eye saccade preceded the head movement, and the gaze response either had the stimulus profile pattern or consisted of one gaze saccade to the final target offset. In response to staircase stimuli, I decreased concomitantly with an increase in D; with pulse-step stimuli, as D increased, I decreased slightly in three subjects and decreased markedly in two subjects. Dissociation between the eye and head movements could clearly be demonstrated with pulse-step stimuli: the first gaze saccade to the target pulse displacement was accompanied by a head movement to the target step offset. We also observed cases in which the gaze saccade to the target step displacement was made simultaneously with the head movement to the target pulse offset. Our study extends previous observations in head fixed condition and illustrates that in the majority of cases, when the head is free and a visual pulse step stimulus is presented, both the saccadic and head systems have the ability to modify or cancel the initial neural command to move to the first target displacement. When this modification takes place in only one system, eye and head movements are dissociated. PMID- 1884759 TI - Head stabilization during various locomotor tasks in humans. II. Patients with bilateral peripheral vestibular deficits. AB - This experiment, which extends a previous investigation (Pozzo et al. 1990), was undertaken to examine how head position is controlled during natural locomotor tasks in both normal subjects (N) and patients with bilateral vestibular deficits (V). 10 normals and 7 patients were asked to perform 4 locomotor tasks: free walking (W), walking in place (WIP), running in place (R) and hopping (H). Head and body movements were recorded with a video system which allowed a computed 3 dimensional reconstruction of selected points in the sagittal plane. In order to determine the respective contribution of visual and vestibular cues in the control of head angular position, the 2 groups of subjects were tested in the light and in darkness. In darkness, the amplitude and velocity of head rotation decreased for N subjects; these parameters increased for V subjects, especially during R and H. In darkness, compared to the light condition, the mean position of a line placed on the Frankfort plane (about 20-30 degrees below the horizontal semi-circular canal plane) was tilted downward in all conditions of movement, except during H, for N subjects. In contrast, this flexion of the head was not systematic in V subjects: the Frankfort plane could be located above or below earth horizontal. In V subjects, head rotation was not found to be compensatory for head translation and the power spectrum analysis shows that head angular displacements in the sagittal plane contain mainly low frequencies (about 0.3-0.8 Hz). The respective contribution of visual and vestibular cues in the control of the orientation and the stabilization of the head in space is discussed. PMID- 1884760 TI - Human ocular torsional position before and after unilateral vestibular neurectomy. AB - The static ocular torsional position of both eyes of 23 patients was measured by means of fundus photographs one day before and one week after unilateral vestibular neurectomy for the treatment of acoustic neuroma, Meniere's disease or paroxysmal vertigo. The results showed that in all patients the vestibular neurectomy caused both eyes to tort (i.e. to roll around the visual axis) toward the side of the neurectomy when measured one week after operation. The extent of this torsion was an average of 9.5 degrees one week after operation and there was no statistically significant difference in the average magnitude of the torsion in the two eyes. In 8 of these patients, additional measurements were made at intervals up to one year after operation and it was found that in these patients there is a significant reduction in torsion over time from an average of 10.2 degrees one week after operation to an average of 2.8 degrees by 16 weeks after operation. The change in torsional eye position following the neurectomy was accompanied by a change in the perceived visual orientation of a small (9.5 degrees visual angle) illuminated horizontal line at a straight ahead eye level position in an otherwise completely darkened room. One week after operation when asked to adjust the line to the perceived gravitational horizontal by rotating it in roll (i.e. around an X axis), patients who had had a right vestibular neurectomy consistently set the line so that the right side of the line (from the patient's point of view) was below the true gravitational horizontal. Similarly patients after a left neurectomy consistently set the line so that the left side of the line was below the true gravitational horizontal. There is a high correlation (r = 0.95) between the direction and magnitude of the change in torsional eye position and the direction and magnitude of the change in the perceived visual horizontal one week after operation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1884761 TI - Integration of sensory information during the programming of precision grip: comments on the contributions of size cues. AB - Evidence has recently been given by Gordon et al. (1991a, b) for the use of visually and haptically acquired information in the programming of lifts with the precision grip. The size-related information influences the development of manipulative forces prior to the lift-off, and the force output for larger objects is adjusted for a heavier weight even if the weight of the objects is kept the same. However, the size influences on the force output were small compared to the relative effects of the expected weight in previous trials (Johansson and Westling 1988). In the present study, both the size and weight of objects were changed between consecutive lifts to more fully determine the strength of visual size cues. During most trials, the size and weight covaried (i.e. the weight was proportional to the volume). However, in some trials, only the size was switched while the weight was kept the same to create a mismatch between the size and weight. The forces were still appropriately scaled towards an expected weight proportional to the volume of the object. It was concluded that visual size cues are highly purposeful. The effects were much larger than previously reported and were similar in magnitude to the effects based upon the expected weight. Thus, the small effects reported in the previous experiments may have been a result of conflicting "size-weight" information. PMID- 1884762 TI - A feature of caudate control of focal hippocampal epilepsy: evidence for an anterograde pathway. AB - Previous experimental evidences showed that the caudate nucleus has a modulatory effect on hippocampal epilepsy. The caudate's regulating action might reach the hippocampus either via the septal region or, retrogradely, via the accumbens nucleus. In order to obtain new data about the pathway involved in caudate hippocampal influence the spreading of abnormal activity towards the nucleus accumbens was studied. Furthermore the effects of caudate stimulation in animals with electrolytic lesions of the nucleus accumbens were analyzed. It was observed that abnormal penicillin-induced activity spreaded from the hippocampus to the nucleus accumbens in about 30 minutes. In animals with and without lesions of nucleus accumbens, caudate stimulation brought about a significant decrease in the frequency and amplitude of hippocampal activity. The results suggest that the nucleus accumbens is reached by the spreading of hippocampal epilepsy but does not participate in the control exerted by the caudate nucleus on the hippocampus. Thus the caudate-induced inhibition takes place through an anterograde caudate hippocampal circuit, while at the same time excluding retrograde activation by way of a caudate-accumbens-hippocampal pathway. PMID- 1884763 TI - Otolith-visual interaction in the control of eye movement produced by sinusoidal vertical linear acceleration in alert cats. AB - 1. Eye movement responses were examined in alert cats during sinusoidal vertical linear acceleration. Stimulus frequencies of 0.20-0.85 Hz with a constant amplitude of 10.5 cm (corresponding to 0.02-0.31 g) were used. A random visual pattern was presented to give sinusoidal vertical optokinetic stimuli of similar amplitude and frequency to the up-down motion of the cat. 2. Sinusoidal linear acceleration in the presence of a stationary visual pattern produced robust eye movement responses with near compensatory phase at all stimulus frequencies tested. With both eyes covered, a vertical linear vestibulo-ocular reflex (LVOR) was frequently produced at a stimulus strength corresponding to 0.04-0.31 g. The evoked LVOR was always small, and the overall mean response phase values advanced by as much as 70 degrees at frequencies below 0.56 Hz, indicating that the otolith signals activated by sinusoidal linear acceleration were not, by themselves, converted into compensatory eye position signals under these experimental conditions. 3. Optokinetic stimulation alone produced more lag of response phase as stimulus frequency increased, and the gain of evoked eye movement responses was smaller at higher stimulus frequencies compared to the gain during linear acceleration in the light. Bilateral labyrinthectomies resulted in a significant change of the eye movement responses during linear acceleration when visual inputs were allowed: there was more phase lag at higher stimulus frequencies and a decreased gain at all frequencies tested. These results indicate that the interaction of otolith and visual inputs produces robust eye movement responses with near compensatory phase during sinusoidal linear acceleration in the light. PMID- 1884764 TI - Activity of eye movement-related neurons in and near the interstitial nucleus of Cajal during sinusoidal vertical linear acceleration and optokinetic stimuli. AB - 1. A total of 43 neurons that showed a close correlation with vertical eye movement with a burst-tonic or tonic type response during spontaneous saccades, were recorded within, and in the close vicinity of, the interstitial nucleus of Cajal (INC) in alert cats. Neuronal responses to sinusoidal vertical linear acceleration (0.2-0.85 Hz, amplitude 10.5 cm) and optokinetic stimuli (0.1-1.0 Hz, amplitude 10.5 cm), were examined. 2. All 43 eye movement-related neurons responded to sinusoidal vertical linear acceleration in the presence of a stationary visual pattern in correlation to robust eye movement responses with compensatory phase. Phase and gain values (re stimulus position) of response of individual cells were independent of the stimulus frequencies tested. Of these, 33 cells were examined during linear acceleration without visual input. Most cells (27/33) did not respond even when a weak linear vestibulo-ocular reflex was present (6/27). The remaining 6 cells (6/33) responded to linear acceleration. Their mean phase values advanced by 80 degrees and gain dropped by 55% compared to the responses with visual inputs. 3. Twenty eight of the 43 cells were examined during vertical optokinetic stimuli. The activity of all 28 cells was modulated in correlation to eye movement responses. Response phase showed more lag, and gain decreased as stimulus frequencies increased, similar to optokinetic eye movement responses. 4. The close correlation between the activity of eye movement-related neurons in the INC region and robust eye movements during linear acceleration with visual inputs and optokinetic stimuli suggest that these neurons are involved in some aspect of vertical eye position generation during such stimuli. PMID- 1884765 TI - Spontaneous and NMDA evoked motor rhythms in the neonatal mouse spinal cord: an in vitro study with comparisons to in situ activity. AB - The current paper presents our initial efforts to establish an in vitro spinal preparation for investigating locomotor pattern generation in mice. We have characterized the step cycle timing from EMG activity in the gastrocnemius (G) and tibialis anterior (TA) muscles of freely moving intact adult as well as neonatal mice and then compared those data with rhythmic EMG activity in an isolated spinal cord-hindlimb preparation. The motor output during the first four days of life was evaluated in an effort to identify the optimal post-partum period for in vitro locomotor studies. The in vitro pattern generating capabilities of the lumbosacral region were tested in both nonhemisected and hemisected preparations. Spontaneous as well as NMDA evoked in vitro activity in the antagonist set of hindlimb muscles included sequences of: 1) synchronous bursting; 2) mixed synchrony and alternation; and/or 3) irregular alternations. The alternating bursting observed in vitro was more often an alternation of sequences rather than a cycle-to-cycle phasing between G and TA muscles. In summary, while there was evidence of reciprocal inhibition in neonates, the circuitry for cycle-to-cycle alternation between antagonists was found to be labile. PMID- 1884766 TI - Effects of stimulation of group I afferents from flexor muscles on heterosynaptic facilitation of monosynaptic reflexes produced by Ia and descending inputs: a test for presynaptic inhibition. AB - 1. In the chloralose anesthetized cat, conditioning stimulation of group I flexor afferents depresses the monosynaptic potentials generated by Ia afferents in single spinal motoneurons or in populations of motoneurons without affecting the monosynaptic potentials produced by stimulation of descending fibers in the ipsilateral ventromedial fasciculus (VMF). 2. Heterosynaptic facilitation of monosynaptic reflexes was used to test changes in the presynaptic effectiveness of excitatory inputs with direct connections with motoneurons. We found that the heterosynaptic facilitation of Ia origin was reduced by conditioning stimulation of group I afferents from flexors, without affecting the heterosynaptic facilitation produced by stimulation of the VMF. 3. These results confirm and expand previous observations showing that the synaptic effectiveness of descending fibers synapsing with motoneurons is not subjected to a presynaptic control mechanism of the type acting on Ia fiber terminals, and provide further basis for the use of changes in heterosynaptic facilitation of monosynaptic reflexes of Ia origin as an estimate of changes in presynaptic inhibition of Ia fibers (Hultborn et al. 1987a). PMID- 1884767 TI - Salt-soluble collagen and elastin in the human aorta and pulmonary artery. AB - Collagen and elastin, the major structural components of blood vessels, have a very low turnover. In disease, this rate may be increased and an elevation of the tissue concentration of the soluble degradation fragments might be anticipated. In this preliminary study the concentration of extractable collagen and elastin in the aorta and pulmonary artery of eight human subjects postmortem was determined. The proportion of pulmonary artery collagen and elastin that was soluble was generally either equal to or greater than that in the abdominal aorta. The fraction of collagen that was salt extractable was larger than the soluble elastin fraction. PMID- 1884768 TI - Rat CINC, a member of the interleukin-8 family, is a neutrophil-specific chemoattractant in vivo. AB - Rat cytokine-induced neutrophil chemoattractant (CINC) is a member of the IL-8 family and its human counterpart is MGSA/gro. Rat neutrophil responses in vitro to rat CINC, human IL-8, and human MGSA/gro were studied. CINC concentrations as low as 1 nM induced apparent chemotaxis of rat neutrophils, but human IL-8 and MGSA/gro required concentrations one or two orders higher than that of CINC to attract neutrophils. These data indicate that human IL-8 and MGSA/gro cannot sufficiently substitute for rat counterparts such as CINC in rats. Therefore, the effect of rat CINC on rats was studied. Intradermally injected 10(-10)-10(-7) M CINC dose-dependently caused infiltration of neutrophils. Significant migration of neutrophils appeared by 30 min, and maximum infiltration was observed around 1 2 hr after the injection. CINC induced quick and transient neutrophil accumulation without lymphocyte and monocyte migration or edema formation. CINC, a member of the IL-8 family but a counterpart of human MGSA/gro-related proteins, is a specific neutrophil chemoattractant and can be distinguished from IL-8, which is a chemotactic factor for lymphocytes and neutrophils. PMID- 1884769 TI - Status of hepatic heme and heme oxygenase during Plasmodium yoelii nigeriensis infection in mice. AB - Plasmodium yoelii nigeriensis infection in albino mice caused a significant increase in hepatic heme level, the increase being concomitant with a rise in parasitemia. This elevated heme was found to be associated with all the subcellular fractions except the cytosol, where its content remained unaltered. Activity of heme oxygenase, the key enzyme responsible for catabolism of heme, also increased progressively with rise in parasitemia. Treatment of normal mice with cobalt chloride [60 mg (kg body wt)-1; subcutaneously] brought about a 150% increase in the level of heme oxygenase; similar treatment of infected mice at low parasitemia could induce the enzyme activity while at high parasitemia the enzymic activity remained unaltered as compared to untreated infected mice. In spite of an increased level of heme oxygenase in the cobalt-treated mice, the level of heme did not show any noticeable change. Oral administration of chloroquine [64 mg (kg body wt)-1 x 4 days] brought about a 56% reduction in the level of heme oxygenase of normal animals but there was no change in infected animals when compared with the corresponding untreated infected mice. However, the amount of chloroquine present in livers of normal and infected animals was not significantly different. PMID- 1884770 TI - Testicular damage by high doses of vitamin B6 (pyridoxine) in rats: a light and electron microscopical study. AB - Male Wistar rats were administered daily intraperitoneal injections of 125, 250, 500, and 1000 mg/kg/day of vitamin B6 for 2 and 6 weeks and the histogenesis of the testicular damage was investigated. A reduction of germ cells was not prominent in the 2-week groups, whereas a delay in spermiation, degeneration of elongated spermatids, and Sertoli cell alterations were observed in the 500- and 1000-mg groups, although generally, these were relatively mild. Ectoplasmic specializations (ES), tubulobulbar complexes, and endoplasmic reticulum (ER) in the apical processes of Sertoli cells were irregularly arranged and their disappearance was also retarded. The Sertoli cell cytoplasm was often retracted and condensed. In the 6-week groups, no histological change in the testis was noted with the 125-mg dose. The retardation in spermiation and Sertoli cell alterations similar to those in the 500-mg dose 2-week group were observed in the 250-mg group. In the 500- and 1000-mg groups, germ cells were generally degenerated and markedly reduced in number. Multinucleate germ cells were mingled with anisocytotic germ cells, and openings of intercellular bridges were occasionally found. Sertoli cells also showed more severe alterations, such as focal disappearance of ES in earlier than ordinary stages, marked dilation of the ER, and markedly condensed or electron-lucent cytoplasm. These results suggest that the Sertoli cell damage may induce diverse germ cell degeneration in which retardation of spermiation occurs first. PMID- 1884771 TI - Free amino acids during chronic cyclosporine A toxicity in intact and partially nephrectomized rats. AB - The effects of 40 days of treatment with Cyclosporine A (CSA) on plasma and urine free amino acids were investigated in sham-operated (C) and partially nephrectomized (Pnx) female Fischer 344 rats. High Dose CSA (30 mg/kg/day ip) was associated with reduced weight gain, increased plasma urea nitrogen, and hypoproteinemia in C and Pnx animals. These animals also demonstrated increased plasma levels of alanine, markedly reduced levels of tryptophan, and an increase in urinary excretion of methylhistidines. C but not Pnx animals also showed a significant increase in plasma serine and a decrease in plasma taurine. CSA treatment of group C resulted in a progressive aminoaciduria involving substrates of the neutral and acidic renal amino acid transport systems; however, the renal excretion of taurine and beta-alanine by these animals was markedly reduced as compared to vehicle treated controls. High dose CSA exacerbated aminoaciduria in Pnx animals, but in this group, the excretion of beta amino acids was also increased. Our findings demonstrate that chronic CSA toxicity in rodents with normal renal function is characterized by increased muscle protein catabolism, significant reductions in plasma tryptophan, and an apparent decrease in whole body taurine pools. With the exception of the taurine abnormalities. CSA treatment had similar effects on Pnx animals; however, in this group, CSA-induced pathological changes were superimposed on the changes due to renal insufficiency per se. CSA toxicity as identified by the parameters investigated in this study was no more severe in Pnx animals with moderate chronic renal insufficiency than in controls with intact renal function. PMID- 1884772 TI - Cadmium toxicity in the thyroid gland of pregnant rats. AB - The toxic effects of cadmium on the thyroid gland of pregnant rats were studied with an electron microscope and an X-ray microanalyzer. Serum levels of thyroid hormones (T3 and T4) were also analyzed. Deterioration of the rough-surfaced endoplasmic reticulum occurred in the thyroid follicular epithelium on the fifth day of cadmium treatment. Large intracellular vacuoles, which arose from dilated cisternae of the rough-surfaced endoplasmic reticulum, were fused together, and marked swelling of the mitochondria was also noted. Thyroglobulin-secreting granules at the apical cytoplasm were decreased in number. By energy dispersive X ray microanalysis, cadmium peaks were preferentially obtained from swollen mitochondria in the follicular epithelial cells. Serum levels of T3 and T4 were significantly decreased in cadmium-treated rats dams when compared to those of controls. In the present experiment, cycloheximide also caused degenerative changes in the rough-surfaced endoplasmic reticulum and the disappearance of thyroglobulin-secreting granules. Cycloheximide is a known inhibitor of protein synthesis on cytosolic ribosomes. These results indicated that accumulated cadmium in the mitochondria of thyroid follicular epithelial cells might disturb the oxidative phosphorylation of this organelle and the loss of energy supply possibly caused the inhibition of the synthesis and release of thyroid hormones. PMID- 1884773 TI - Pathogenesis of rickettsial infections emphasis on Q fever. AB - The underlying mechanisms at the organismic, cellular and molecular levels that account for rickettsial pathogenesis are beginning to be revealed. In the case of Coxiella burnetii infection, relatively recent genetic and biochemical data, as well as drug susceptibility studies, indicate a correlation between isolate type and clinical disease--chronic or short-term acute. The use of cultured cells as model host systems has revealed that, indeed, different isolates from the major classified strains of C. burnetii cause different host cell responses. Use of this and other models (guinea pigs, mice) have revealed other characteristics and properties of the rickettsiae and the infected hosts and host cells that may account, in part, for acute disease and persistent infection culminating in chronic disease. The virulence factors involved apparently include the agent's surface lipopolysaccharide; other unidentified factors have not been excluded. Molecular cloning will play a major role in elucidating the roles of these factors and in identifying other virulence determinants. PMID- 1884774 TI - Ecological questions concerning rickettsiae. AB - The past ten years were characterized by the appearance of several "new" transmissible spotted fever group (SFG) rickettsioses, e.g. Israeli, Japanese and Astrakhan fevers. The factors responsible for their establishment probably include the introduction of chemicals from industry, agriculture and the timber industry into natural habitats. Such factors may influence the pathogenicity of these rickettsiae. In this case, in addition to the human influence, the mechanism of the circulation of the agents under natural conditions of both abiotic (climate, etc.) and biotic (flora and fauna) components may play a decisive role. The modern management of breeding domestic animals, indoor and outdoor maintenance, seasonal migrations, new animal foods, stress, etc., can be important factors affecting the biological properties of the Q fever agent. Nonpathogenic rickettsiae, rickettsia-like symbionts and other microorganisms circulating in nature may also influence the pathogenic rickettsiae. Studies on their interrelationships in hosts and vectors may markedly contribute to the understanding of the circulation of pathogenic rickettsiae in nature. Recognition of factors causing the appearance of new rickettsial agents or differences in pathogenicity of rickettsial strains is important not only for the prognosis of rickettsial diseases but also for the prognosis of other infectious diseases. PMID- 1884776 TI - An overview of research on ehrlichiosis. AB - Ehrlichiosis is a disease caused by a group of rickettsiae, known as ehrlichiae, which parasitize circulating leukocytes of man and a variety of domestic and wild animals. A characteristic morphologic feature of ehrlichiae is their occurrence in membrane-bound vacuoles in the cytoplasm of leukocytes, forming inclusions that contain variable numbers of organisms. The tick is the apparent vector of ehrlichiae, but such evidence is not available for all species. PMID- 1884775 TI - Epidemiology of rickettsial diseases. AB - Rickettsial diseases have a diversity of epidemiologic characteristics reflective of the variety of ecologic situations in which the obligate intracellular bacteria are transmitted to humans. For the spotted fever group (SFG) rickettsiae, Rickettsia typhi, R. tsutsugamushi, Coxiella burnetii, and the human ehrlichial agent, humans are a dead-end host who plays no role in the maintenance of the organism in nature. All rickettsioses exist as zoonoses. Moreover, all rickettsiae are found in infected arthopods, which generally serve as the natural hosts and can transmit the infection to the next generation of ticks, mites, chiggers, or fleas. From our anthropocentric viewpoint, Q fever aerosol infection from parturient animals and Brill-Zinsser disease ignited epidemics of louse borne epidemic typhus are exceptions. However, silent cycles of C. burnetii in ticks and R. prowazekii in the flying squirrel flea may have maintained these agents in transovarial or enzootic cycles for eons before humans and their domestic animals arrived on the scene. Thus, the epidemiology of rickettsial diseases must be recognized as an unfortunate aberration of the rickettsial economy. Several excellent reviews of rickettsial ecology contain a wealth of useful information. PMID- 1884777 TI - Biology of ehrlichiae. AB - The isolation and cultivation of the agent of Potomac horse fever, Ehrlichia risticii, by Holland, Ristic, et al., afforded Weisburg et al. an opportunity to examine its phylogeny. E. risticii is clearly related to the genus Rickettsia and not to chlamydiae. A reevaluation of the significance of phenotypic characteristics is thus required, since ehrlichiae, in some respects, resemble chlamydiae. For example, unlike rickettsiae, ehrlichiae and chlamydiae multiply in the phagosome of their host cells, but may not have the same mechanism of inhibition of phagosome-lyososome fusion. Rickettsiae, which multiply in the cytoplasm, may have a mechanism of survival in the phagosome similar to that of the ehrlichiae, but, in addition, utilize a phospholipase, which permits prompt escape from the phagosome. Rickettsiae, as most Gram negatives, multiply by binary fisson. Chlamydiae, on the other hand, undergo a cycle of development. Elementary bodies (EB) infect, but do not divide, while the reverse is true of reticulate bodies (RB). Ehrlichiae superficially resemble chlamydiae rather than rickettsiae, but ehrlichiae have not yet been submitted to the rigorous criteria of separation of EB and RB. Investigations in our laboratory of the metabolic activities of E. risticii and E. sennetsu link them to the rickettsiae and not to the chlamydiae. Ehrlichiae and rickettsiae, but not chlamydiae, derive some ATP from their catabolic activities. In conclusion, in further investigations of the monocytic ehrlichiae, it is safer to be guided by what we know of rickettsiae, than chlamydiae. PMID- 1884778 TI - Diagnosis of rickettsial diseases: a perspective. AB - Rickettsioses have nonspecific clinical manifestations, making them difficult to diagnose in a clinical setting. Laboratory testing is usually needed to confirm the diagnosis. Rickettsial isolation is a sensitive and specific diagnostic technique, but the hazards associated with handling pathogenic rickettsiae usually preclude isolation attempts in most laboratories. Rickettsiae can also be detected in infected tissues by fluorescein-labeled antisera or by immunoperoxidase staining, but these techniques lack sensitivity, except when applied to postmortem tissue specimens. However, rickettsial DNA can be detected in acute phase blood specimens by polymerase chain reaction (PCR) technology, and this technique offers the prospect of prompt diagnosis and treatment. Serologic testing remains the most frequently used approach to diagnosis, although antibody tests usually fail to identify rickettsioses early enough to affect the management of individual patients. Available serologic techniques vary considerably in their sensitivity and specificity. Enzyme-linked immunosorbent assays (ELISA) are extremely sensitive, but the general unavailability of specific diagnostic antigens reduces the specificity of this and other serologic techniques. Molecular characterization of rickettsial antigens may soon allow the production of peptide antigens that are specific for each species and could maximize the specificity of test results. No diagnostic technique has any value unless it is applied successfully to the appropriate patient population. Improved surveillance of rickettsial diseases is urgently needed to identify specific areas in which rickettsioses are endemic. Such surveillance data would promote awareness of rickettsioses among local physicians and increase the probability that individual patients with rickettsioses would be identified promptly and receive appropriate therapy early in the course of their illness. PMID- 1884780 TI - Control of rickettsial diseases. AB - Prevention of rickettsial infections is aimed at individual control and epidemic measures (especially in epidemic typhus), vector and rodent control, milk pasteurization (in Q fever), chemoprophylaxis and immunoprophylaxis. In vector and rodent control, the main obstacle is the rise in resistance to insecticides and rodenticides. For this reason in vector control, apart from insecticides, enhancement of the natural immunity acquired by animals in response to tick infestation and vaccination with concealed tick antigens as well as the use of hormones, chemosterilants and genetic manipulation can also be considered. For short-term high-risk exposure, doxycycline may be an effective prophylaxis of illness but may not prevent infection with scrub typhus or spotted fever group rickettsiae. At present, for specific prevention by vaccination, only Q fever vaccines are available for common use. However, development of subunit vaccines, namely immunogenic rickettsial proteins, cloned and expressed in Escherichia coli, seems to be very promising. PMID- 1884779 TI - Antibiotic treatment of rickettsiosis, recent advances and current concepts. AB - The author reviews the recent advances in the treatment of Mediterranean Spotted Fever and Q fever. In mediterranean spotted fever (M.S.F.), in vitro and preliminary in vivo data support the place of quinolones and josamycin in the treatment of M.S.F. In children josamycin could become the first choice drug as well as in pregnant woman. In Q fever chronic disease should be treated using a combination of antibiotic (doxycycline + quinolones) for a minimum of 3 years. PMID- 1884781 TI - The role of the World Health Organization in the control of rickettsial diseases. AB - The World Health Organization (WHO) pays great attention to the problem of rickettsial diseases. A network exists of Collaborating Centres for Rickettsial Reference and Research, which are designated by WHO. A WHO Consultation on the Laboratory Diagnosis of Rickettsial Diseases was held in 1987. In accordance with the recommendations of this consultative group, WHO first established The Project on Global Surveillance System for Rickettsial Diseases, with the immediate objective of obtaining reliable data on the global prevalence and distribution of rickettsial diseases. This information should contribute directly to the principal objective of reducing morbidity and mortality due to rickettsial diseases. An additional objective is to identify and characterize strains of pathogenic rickettsiae from various localities throughout the world. The final objective of the above study is to transfer the existing diagnostic technology to laboratories in developing countries. Under the auspices of this Project a diagnostic kit was developed for identification of antibodies with antigens of R. prowazekii and R. conorii in the indirect immunofluorescence test. About 20 laboratories in various countries are participating in this Project. Training courses have been organized for participants from countries in Africa and South East Asia. The first stage of the Project will be evaluated in 1991 and, depending on the outcome of the first stage, a larger programme would be considered for subsequent years. PMID- 1884782 TI - Rickettsiae and rickettsioses in Portugal. AB - The only rickettsiae recorded in Portugal till now were Rickettsia conorii and Coxiella burnetii. Boutonneuse fever is one of the most important transmissible diseases in Portugal. Though the annual number of cases is not exactly known, it is estimated to be not far from 20,000 in some years. Q fever is the other rickettsiosis widely disseminated throughout the country. The serological prevalence and the incidence of those rickettsioses in Portugal are presented in this communication. In recent research in southern Portugal, about 4,000 adult ticks of nine species were screened by the haemocyte test for rickettsiae and rickettsia-like organisms (RLO). In addition to R. conorii three microscopically different RLO were observed. Two of them, i.e. ovoid and bacillary-like, were positive in the immunofluorescence test with spotted fever (R. conorii) antiserum. The first occurred mainly in Rhipicephalus sanguineus ticks, the second one also in other tick species. The latter agent was cultivated in half engorged R. sanguineus females and in Vero cells. The third organism was found in R. sanguineus, where it exhibited a massive infestation in haemocytes resembling that seen in experimentally infected ticks with C. burnettii, but not being this agent. The investigation of the isolates and their identification and characterization are being continued. PMID- 1884784 TI - Extensive examination of different tick species for infestation with Coxiella burnetii in Slovakia. AB - Between 1987-1989 almost 7000 adult Ixodes ricinus, Dermacentor reticulatus, Dermacentor marginatus, Haemaphysalis concinna, Haemaphysalis punctata and Haemaphysalis inermis ticks collected in all 38 districts of Slovakia were screened for the presence of Coxiella burnettii. The proportion of ticks containing C. burnetii as indicated by the haemocyte test was less than 3%. Attempts to recover C. burnetii by inoculation of yolk sacs of embryonated hen eggs from pools of 1-6 specimens of haemocyte test positive ticks resulted in the isolation of 10 rickettsial strains. Six strains were recovered from I. ricinus, the remaining ones from single pools of D. reticulatus, D. marginatus. H. concinna and H. inermis ticks. In addition to the previous recovery of C. burnetii from H. punctata ticks, the agent was thus isolated from all important ticks living in Slovakia. The agent was found in tick habitats regardless of the latitude and altitude in the entire country. These results are not consistent with the negligible number of Q fever cases occurring in past years in Slovakia. PMID- 1884783 TI - Studies of a "new" rickettsiosis "Astrakhan" spotted fever. AB - The acute febrile disease with characteristic rash seen in Astrakhan region and named as "viral exanthema of unknown etiology" was proved to be a spotted fever group rickettsiosis. Serological examination of humans from endemic areas by complement fixation test revealed antibodies to R. conorii, R. akari and strains Netsvetaev and AR-74 of R. sibirica in titres from 20 to 640 in sera from ill persons. Of 429 sera from healthy persons, 5.1% were serologically positive in a titre of 20-40. The presence of spotted fever group rickettsiae was detected in 8 of 104 Rhipicephalus sanguineus ticks removed from dogs and tested by haemocyte test with Gimenez staining and indirect immunofluorescence technique. Attempts at isolation of rickettsiae in guinea pigs and cell cultures resulted in appearance of specific spotted fever group rickettsiae antibodies in guinea pigs (4 of 8 samples examined were positive) and detection of rickettsiae by immunofluorescence technique in cell cultures (in 2 of 12 samples tested). PMID- 1884785 TI - Epidemic of Q fever in Leszno district in Poland. AB - In 1988 an epidemic of Q fever was detected in Leszno district. During 1973-1985 all 28,066 cattle tested for C. burnetii antibodies were found to be negative. The first seroconversions were found in cows which produced stillborn young. In the following years the number of seropositive cattle increased from 8.4% in 1987 to 21.6% in 1989. In 1988 all animal workers in the district were tested for C. burnetii antibodies. Of 4,264 persons tested, 1,451 (34%) were seropositive. A detailed study of workers and animals on one farm were performed. A herd of animals was found to be seropositive (32.1%), 68% of workers in direct contact with infected animals were seropositive and 29% of persons drinking raw milk. C. burnetii strains have been isolated from ticks, wild animals and birds hunted in close proximity of the farm. The dynamics of C. burnetii infection among animals and humans in this district and the fact that there is no importation of animal herds suggests that the possible route of introduction of Q fever in this area may be with imported semen or breeding bulls. The presence of C. burnetii in ticks and wild animals indicates the transfer of Q fever to the natural environment and its maintenance in this territory. PMID- 1884787 TI - [The objective evaluation of the action of agents causing a pathological attraction]. PMID- 1884786 TI - [The effect of morphine and naloxone on the interaction of afferent signals of differing modalities in the spinal cord]. AB - The effect of the electrical nerve stimulation with low (2-4 V, 100 Hz, 5 min) and high (45 V, 1 Hz, 1 min) intensity on the nociceptive responses in the ventrolateral tracts was studied in unanesthetized rats with the transsected spinal cord. Both kinds of stimulation reduced nociceptive responses but the effect of low-intensity stimulations was diminished when they were repeated and was absent over 24 hours after spinalization. The effect of low-intensity stimulation was abolished by naloxone (0.1 and 1 mg/kg) and was reduced during the antinociceptive effect of morphine (1 and 4 mg/kg). The effect of high intensity stimulation was preserved over 24 hours after spinalization and after repeated stimulations. It was not changed by naloxone and morphine. PMID- 1884788 TI - [Changes in the cerebral hemodynamics under the influence of piracetam and fenibut during motion sickness]. AB - In the experiments on conscious rabbits with the electrodes implanted in the brain it was found by the methods of hydrogen clearance and polarography that piracetam (50 and 500 mg/kg) and phenibut (50 mg/kg) induced a decrease of the local blood flow in the cortex of the frontal, temporal and occipital regions and the total cerebral blood flow. The administration of the drugs before tilting prevents the occurrence of vasodilatation in the brain and results in a decrease of the blood flow in the cortex and in the confluence of the cerebral venous sinuses that is thought to be connected with the mechanism of an increase of the vestibular stability under the influence of GABA derivatives. PMID- 1884790 TI - [The anti-ischemic properties of verapamil and its effect on myocardial functional potentials in coronary artery occlusion]. AB - The effect of verapamil on the functional state of the ischemic myocardium, the myocardial tolerance to ischemia and the processes of urgent adaptation of the heart in the coronary artery occlusion was investigated in the experiments on anesthetized open-chest cats. Verapamil was shown to exert the dose-dependent anti-ischemic action, to increase the myocardial tolerance to ischemia, to suppress the response to the physiological saline infusion and not to change adrenoreactivity of the ischemic myocardium at the coronary artery compression. PMID- 1884789 TI - [The linking of the basic functions of the cerebral vessels under the influence of adrenergic substances and general anesthetic agents]. AB - In chronic experiments on conscious and quiet rats norepinephrine, isoproterenol, ether, hexenal and ketamine narcosis decreased the cerebral fraction of cardiac output but increased transcapillary filtration in tissues of rubidium chloride and blood supply in the capacitive part of blood vessels. The changes produced by pyroxan, obsidan and ornid in the same conditions were insignificant. A decrease of the cerebral fraction of cardiac output, an increase of transcapillary filtration of rubidium in the brain tissues and regional blood supply took place under the action of pyroxan, obsidan and ornid in experiments with immobilization of rats. PMID- 1884791 TI - [The comparative sensitivity of isolated arteries and atrium from the cat to m cholinoreceptor agonists]. AB - A comparative assessment of the activities of some agonists of M-cholinoreceptors was made on the isolated mesatone-treated segments of arteries of various localization and the isolated left atrium of the cat. It was found that by the sensitivity to cholinomimetics the cat arteries may be divided in 2 groups: high- and low-sensitive (the latter include the aorta and renal artery). The left cat atrium is less sensitive to the agonists than the high-sensitive arteries and possesses approximately the same sensitivity to M-cholinomimetics as the aorta and renal artery. PMID- 1884792 TI - [The prospects for the pharmacological correction of the microcirculatory disorders in patients with chronic ischemic heart disease]. AB - The state-of-the-art knowledge of the effects of beta adrenoblockers, calcium antagonists, nitrates, antioxidants, acetylsalicylic acid, anti-inflammatory non steroidal drugs, pyridinol-carbamate and nicotinic acid on the microcirculatory bed and the condition of the transcapillary metabolism in patients with stable angina pectoris is presented. The possibilities of the negative actions of the drugs on the microcirculation are determined. The possibility of the choice of a pharmacological impact for correction of microcirculatory disorders in patients with stable angina pectoris is shown. PMID- 1884793 TI - [The comparative influence of pyrazidol, inkazan and other antidepressant monoamine oxidase inhibitors on the pressor effect of tyramine]. AB - In experiments on conscious normotensive male Wistar rats the new antidepressants, reversible MAO-A inhibitors, pyrazidole and incazane, as well as moclobemid increased the pressor effect of orally administered tyramine. The drugs potentiated also the pressor effect of intravenous tyramine. More prolonged potentiation of tyramine action was produced by moclobemid, less prolonged by incazane. The potentiation by the studied MAO-A inhibitors of the pressor effect of tyramine reflects the inhibition of the activity of MAO-A and the first-pass metabolism of tyramine in the gut and liver, as well as the inhibition of intraneuronal MAO activity in noradrenergic nerve endings and the potentiation of sympathetic activity. PMID- 1884794 TI - [The influence of calcium ion antagonists on the effects of bradykinin]. AB - On the isolated segments of the ileum of the guinea-pig, anesthetized and nonanesthetized rats and mice it was established that calcium ion antagonists from different chemical series exert the nonspecific antibradykinin action, reducing the main biological effects of bradykinin--myotropic, depressor, nociceptive and microcirculatory. To a greater extent the mentioned properties show up in the derivatives of 1,4-dihydropyridine (phoridon, etc.) that may play the certain role in the therapeutic action of the drugs in the diseases associated with the activation of the kinin system of the organism. PMID- 1884795 TI - [Experimental research on the safety of the new gestagen preparation acetomepregenol]. AB - In the experiments on mature females of 50 rats, 10 rabbits, 8 dogs it was established that a new gestagenic drug acetomepregenol was not toxic both for pregnant and nonpregnant animals. The two-month administration of the drug in the therapeutic and maximal doses did not exert the irreversible effects on the reproductive function and did not influence the embryonal and postnatal development of the offspring. A single administration of acetomepregenol in the critical periods of pregnancy was found to exert the embryotoxic effect which did not manifest itself during daily administration of the drug from the 6th through the 16th days of pregnancy. PMID- 1884796 TI - [The thrombolytic activity of acylated activator complexes of plasmin streptokinase with different rates of reactivation]. AB - In the experiments on guinea-pigs with venous thrombosis there were studied the fibrin- and thrombolytic effects of streptokinase, the plasmin-streptokinase complex and the acylated derivatives of the complex with various rates of reactivation. It was established that the acylated derivatives of the plasmin streptokinase complex possess greater stability in the blood flow and lead to more prolonged stimulation of fibrinolysis at less magnitude of its systemic activation. Due to this the acylated derivatives of the plasmin-streptokinase complex produce less pronounced fibrinogenolysis. In connection with a high affinity to fibrin their thrombolytic action does not depend on the systemic activation of fibrinolysis. PMID- 1884797 TI - [The effect of heparin in vasorenal hypertension on the rheological properties of the erythrocytes and on the electrolyte balance of the blood and of the wall of the abdominal aorta]. AB - In hypertension there was shown an increase of the erythrocyte suspension viscosity coefficient, a decrease of the transmural difference of the abdominal aorta potentials and the erythrocyte charge at a lowering of the level of the studied electrolytes in plasma, the abdominal aorta wall and an increase of sodium content in erythrocytes. Heparin corrected the changes in the coefficient of viscosity and charge of erythrocytes, the transmural difference of potentials, potassium and magnesium levels in erythrocytes, sodium level in the abdominal aorta wall induced by hypertension. On the whole there was observed no levelling by heparin of electrolyte imbalance in the erythrocyte-plasma-abdominal aorta wall system. PMID- 1884798 TI - [The effect of hydrocortisone on the activity of the alkaline proteinase systems in the rat thymus]. AB - The effect of single and chronic administration of hydrocortisone on the thymus proteinase activity in the alkaline pH range was studied on rats. The presence in the thymus of the glucocorticoid-sensitive alkaline proteinase system induced by hydrocortisone was shown. A decrease of the activity of the system in the adrenalectomized animals was found. The possible relationship between the thymolytic effects of hydrocortisone and the increased activity of the alkaline proteinase systems of the thymus is concluded. PMID- 1884799 TI - [The effect of the carnitine biosynthesis inhibitor mildronate on the lipid metabolic indices of rats]. AB - The course administration of a carnitine biosynthesis inhibitor mildronate (100 mg/kg, orally, for 10 and 30 days) was shown to increase the rat blood serum concentration of free fatty acids. By the 30th day of the treatment no changes in the rat myocardium contents of free fatty acids, triglycerides and cholesterol were found that along with the prevention of the accumulation of long chain metabolites of fatty acids in the heart under conditions of adrenergic actions indicated the pathogenetically right approach to the treatment of ischemic heart disease with mildronate. PMID- 1884800 TI - [The activating action of mercaptobenzimidazole derivatives on peritoneal macrophages]. AB - It was established that derivatives of mercaptobenzimidazole (bemitil, methoxybemitil, 5-ethoxy-2-ethylmercaptobenzimidazole hydrochloride) in a dose of 25 mg/kg stimulate the mouse peritoneal macrophages by increasing their phagocytic activity and phagocytosis index. Among the studied agents 5-ethoxy-2 ethylmercaptobenzimidazole hydrochloride possesses the greatest effect. The increase of phagocytosis processes was shown to be accompanied with a growth of the number of macrophages reducing nitroblue tetrazolium in diphormazan and with an enhancement of secretion of lysosomal enzymes. PMID- 1884801 TI - [The influence of glucosamine on the antiexudative effect of nonsteroidal anti inflammatory agents]. AB - The study of the antiexudative activities of voltaren, indomethacin and piroxicam in combination with glucosamine on the model of carrageenan inflammation showed that the combination makes it possible to decrease the effective doses of nonsteroidal anti-inflammatory drugs by 2-2.7 times with the preservation of the pronounced antiexudative activity. A diverse influence of aminosugar on the anti inflammatory effect of nonsteroidal anti-inflammatory drugs depending on the sequence and routes of administration is connected with their membrane mechanisms and metabolic features of amino sugar. PMID- 1884803 TI - [The pharmacokinetics of the marker preparations antipyrine and sulfadimezine in children suffering from bronchial asthma]. AB - The pharmacokinetics of marker drugs antipyrine (phenazone) and sulfadimezine (sulfadimidine) was studied in 50 children with bronchial asthma and preasthmatic diseases and 6 healthy children. A decrease of antipyrine elimination rate in the patients depending on the severity, duration and phase of the disease was revealed. The specific character of xenobiotic detoxication in sick children confirms the dissociation of the functioning of the enzymatic systems of microsomal oxidation and acetylation. The necessity of the pharmacological control in bronchial asthma in children is discussed. PMID- 1884802 TI - [Pikamilon pharmacokinetics in animals]. AB - Pycamilon was shown to be rapidly absorbed in the blood (tmax = 0.23 h), to penetrate well through the blood-brain barrier and to be intensively uptaken by the animal organs and tissues and to be eliminated mainly in the urine (t1/2 = 0.51 h). The drug bioavailability at oral administration to mice is 21.9%, and to rats from 53 to 78.9% (according to the urinary excretion data). PMID- 1884804 TI - [The effect of microsomal enzyme inducers on the renal transport of verografin (triombrast)]. AB - In experiments on rats and dogs it was shown that administration of phenobarbital (20 and 50 mg/kg orally, 4 days), benzonal (35 mg/kg, orally, 4 days), zixorine (200 mg/kg orally, 4 days) and 3-methylcholanthrene (20 mg/kg subcutaneously, 2 days) caused on the 3rd day following the last administration of the drug a reduction of verografine secretion in the kidneys. After administration of phenobarbital to dogs (20 mg/kg orally, 4 days) a decrease of renal transport of verografine within 4-5 weeks was observed. PMID- 1884805 TI - [The "phenomenon of ethanol preference"]. AB - The problem of using the "phenomenon of ethanol preference" under conditions of a free choice between ethanol and water as a behavioural model of alcoholism is discussed. The methodical aspects of the model are considered: the regimen of the animals' keeping, the criteria of preference, the concentrations of ethanol solutions, the schedule of presentation of the solutions. There was shown the principal similarity between the changes in the behaviour and biological parameters of the animals preferring ethanol and the changes observed in the man suffering from chronic alcoholism. It is concluded that despite the imperfection of the model the "phenomenon of ethanol preference" remains fairly valuable for studying the etiopathogenesis of alcoholism and developing the methods of the therapeutic action on the patient. PMID- 1884806 TI - [The 5-fluorouracil content of the pancreas and parapancreatic tissues when it is administered regionally into the tissue of the round ligament of the liver]. AB - In the experiment on 31 dogs there was shown a significant increase of 5 fluorouracil concentrations in the pancreas and parapancreatic tissues with regional methods of its administration in the fat of the round ligament of the liver. A more prolonged preservation of the drug concentrations at the therapeutic level in the blood was observed. The most effective method of the cytostatic therapy is the regional lymphotropic method. PMID- 1884809 TI - Setting up your retirement plan: know the basics. PMID- 1884808 TI - [The interaction of drug agents]. PMID- 1884807 TI - [Cholinesterase activity and the rate of the maturation of the sensorimotor reflexes in the progeny of white rats administered carbophos during pregnancy]. AB - Female mongrel albino rats were administered orally carbophos in a dose of 10 mg/kg (1/100 of LD50) on the 11th, 13th, 15th and 17th days of pregnancy. The antenatal administration of carbophos was shown to produce combined disturbances of the postnatal development of the mongrel albino rats manifesting themselves in changes of the maturation of sensomotor reflexes, cholinesterase activity, increased addiction both to carbophos and ethanol. PMID- 1884810 TI - Oral manifestations of AIDS: a pictorial guide. PMID- 1884811 TI - Infection control: systems that make the grade. PMID- 1884812 TI - Tax planning: don't overlook state taxes. PMID- 1884813 TI - Local anesthetics: the esters. PMID- 1884814 TI - Local anesthetics: the amides. PMID- 1884815 TI - Oral manifestations of AIDS: the dentist's role in treatment. PMID- 1884816 TI - Economic and investment outlook for the 1990s. PMID- 1884817 TI - Endodontics for the general practitioner. PMID- 1884818 TI - How to get the most out of your accountant. PMID- 1884819 TI - Maximize the value of your pension plan distributions. PMID- 1884820 TI - Topical anesthetics. PMID- 1884821 TI - Malpractice: making the best of a bad situation. PMID- 1884822 TI - Computerize your practice: practical advice. PMID- 1884823 TI - Oral manifestations of AIDS: Part 3. PMID- 1884824 TI - Solo-group practice: consider the down side. PMID- 1884825 TI - Improve your practice with an SBA loan. PMID- 1884826 TI - National and regional survey of dentists' incomes. Compare your 1990 gross and net to the averages reported here. PMID- 1884827 TI - Hygienist incentives: the solution at last? This plan will boost office productivity and increase both the dentist's and hygienist's income. PMID- 1884828 TI - GRATEFUL MED: the world's dental knowledge at your fingertips. The "Gateway to MEDLARS" gives dentists new ways to keep current. PMID- 1884829 TI - Cosmetic dentistry. PMID- 1884830 TI - Marketing workshop. Dental implants. PMID- 1884831 TI - Are you following the latest pension plan rules? PMID- 1884832 TI - How to increase your net. PMID- 1884833 TI - Implantology. PMID- 1884834 TI - How to shockproof your investment portfolio. PMID- 1884835 TI - Posterior restorations. PMID- 1884836 TI - Blood testing debate. PMID- 1884837 TI - Technology enhances this preventive practice philosophy. PMID- 1884838 TI - "Doctor, make me a star"! PMID- 1884839 TI - The team approach to dental implants. PMID- 1884841 TI - When to buy equipment. PMID- 1884840 TI - Recall System Management--2. Designing a fool-proof recall system that works. PMID- 1884842 TI - Planning a move. PMID- 1884843 TI - Dealing with the insurance nemesis. PMID- 1884844 TI - Getting comfortable with claims-made liability coverage. PMID- 1884845 TI - A dentist-owned malpractice insurance company? PMID- 1884846 TI - Effects of niobium filtration and constant potential on the sensitometric responses of dental radiographic films. AB - Two half-wave self-rectified dental X-ray units and two constant potential units were compared with respect to the sensitometric properties of D- and E-speed emulsions. The effects of additional niobium filtration on the half-wave beams were explored. Important differences between the responses of the two emulsions identified inadequacies in the International Standards method for determining film speed. The constant potential units gave values of speed within the range of the half-wave rectified units. Additional niobium caused an increase in the film speed produced by the half-wave units, especially in the case of the lower kilovoltage, less filtered beam. For all beam qualities investigated, the film speed was related to the half value layer. No specific effects of the constant potential supply, nor of the niobium filtration were identified. Film contrast was unrelated to beam quality, and differed in several respects between the two emulsions. PMID- 1884847 TI - Image analysis of microsialograms of the mouse parotid gland using digital image processing. AB - We compared two digital-image feature-extraction methods for the analysis of microsialograms of the mouse parotid gland following either overfilling, experimentally induced acute sialoadenitis or irradiation. Microsialograms were digitized using a drum-scanning microdensitometer. The grey levels were then partitioned into four bands representing soft tissue, peripheral minor, middle sized and major ducts, and run-length and histogram analysis of the digital images performed. Serial analysis of microsialograms during progressive filling showed that both methods depicted the structural characteristics of the ducts at each grey level. However, in the experimental groups, run-length analysis showed slight changes in the peripheral duct system more clearly. This method was therefore considered more effective than histogram analysis. PMID- 1884848 TI - Effect of size of region of interest on precision of bone mineral measurements of the mandible by quantitative computed tomography. AB - The effect of size and shape of the region of interest (ROI) on the precision of the measurements of bone mineral content of mandibular bone by quantitative computed tomography (QCT) has been studied. A dry mandible and a series of calcium carbonate rods (density: 119.6 mg cm-3, 461.2 mg cm-3 and 939.0 mg cm-3) were used. The precision of measurements of the ROI for sizes less than 1 cm2 was very low, but the shape did not have any influence on the precision if the material examined was either homogeneous or if it was heterogeneous from always the same area. Higher precision was found when the ROI was more than 1 cm2. The size of ROI is a critical factor in the measurement of bone mineral content in the mandible by QCT. PMID- 1884849 TI - Recent trends in imaging the salivary glands. PMID- 1884850 TI - Differential diagnosis of submandibular cystic lesions by computed tomography. AB - A retrospective analysis of 35 submandibular cystic lesions was undertaken to assess the usefulness of CT in their differential diagnosis. Lesions were analysed on the basis of extent, shape and density. It was found that all those lesions that extended into both the sublingual and the anterior part of the submandibular spaces could be diagnosed as ranulas (10/10) and all those limited to the posterior part as lateral cervical cysts (8/8). Those lesions that extended to the sublingual, but not the anterior part of the submandibular space, were dermoid cysts if they had a smooth margin (2/2), and probably ranulas when it was concave (4/5). Those lesions that extended into the anterior part of the submandibular but not the sublingual space were ranulas on the basis of a multilocular or concave margin (3/3), but if they had a smooth margin (3/7) they could not be differentiated from dermoid cysts (4/7). Although CT density was less valuable for the differential diagnosis, both ranulas and dermoid cysts could be excluded if it was similar to that of muscle. PMID- 1884851 TI - Radiological visibility of small artificial periapical bone lesions. AB - Previous studies have indicated that the visibility of periapical lesions on a radiograph is determined by erosion of either the cortex or the junction area between cortex and spongiosa. In the present study, artificial lesions, varying in diameter from 1.6 to 4.5 mm, were produced with a round dental bur at 32 sites in 27 blocks from four dried human mandibles embedded in paraffin and radiographed under standardized conditions. The radiographs were evaluated by three observers with differing degrees of radiological experience, and the results expressed as Mean Visibility Index (MVI) and Mean Difference Index (MDI). Six parameters were measured at each site, thickness of the bone, of the cortex and of the spongiosa, density of the spongiosa, cortex/spongiosa ratio, and erosion of the cortex, and their correlation with the two indices determined by stepwise and multiple regression. It was found that MVI was significantly associated not only with the erosion of the cortex but also the density of the spongiosa and the diameter of the lesion. MDI was found to be associated mainly with cortex erosion. PMID- 1884852 TI - A comparison of panoramic radiography with computed tomography in the planning of implant surgery. AB - The accuracy of panoramic radiography and computed tomography (CT) in the evaluation of depth of the mandible at recipient implant sites was compared by measuring the distance between the edentulous bony crest and the superior border of the inferior alveolar canal in a group of ten patients. Distortion was calculated using the metal ball technique for the panoramic radiographs and the computer scale for the CT scans. The precise distance between the bony crest and inferior alveolar canal was determined from postoperative radiographs from the known length of the implants. It was found that although CT scans are more precise, panoramic radiography is sufficiently accurate for routine clinical purposes. CT scans have, however, an additional advantage in presurgical planning, since they reveal the horizontal dimension and shape of the mandible, and the topography and buccolingual location of the inferior alveolar canal. PMID- 1884853 TI - Adenomatoid odontogenic tumour: a report of two large lesions. AB - Adenomatoid odontogenic tumours with a diameter of more than 4 cm are uncommon. Two cases, both measuring in excess of 7 cm, are described and the differential diagnosis discussed. The progressive growth and cortical perforation in these two cases support the view that it is a benign neoplasm rather than a hamartoma. PMID- 1884854 TI - Drug-induced versus drug-triggered pemphigus. AB - 112 cases of induced pemphigus were reviewed. The causative drugs were divided into three groups according to their chemical structure, and the clinical, prognostic and laboratory characteristics were analyzed and compared. Our literature screening indicates that the biological progress and clinical course of the disease depend upon the type of the inducing/triggering drug in the majority of patients. Patients with penicillamine-induced pemphigus or with pemphigus induced by SH drugs (drugs containing a sulfhydryl radical) showed spontaneous recovery in 39.4 and 52.6%, respectively, once the drug was discontinued. Patients whose pemphigus was induced by other drugs showed spontaneous recovery in only 15% of the cases. These results indicate that in patients with pemphigus induced by penicillamine (or SH drugs), the drug plays a major role in the pathogenesis of the disease, as compared to patients with pemphigus induced by other drugs. It seems that penicillamine (and SH drugs) actually induces pemphigus in most of the cases, whereas other drugs only trigger the disease in patients with a previous predisposition. PMID- 1884855 TI - Rhythm of sebum excretion during the menstrual cycle. AB - We studied by the Sebutape technique variations in the sebum excretion and in the number of active sebaceous glands during 3 consecutive menstrual cycles. In seborrheic women we found cyclic changes with a maximum sebum excretion during the week before menstruation. In women with a low sebum production, no changes were found. PMID- 1884856 TI - Prevalence of atopy in vitiligo. A preliminary report. AB - 59 patients suffering from vitiligo were investigated anamnestically and clinically with intradermal (prick tests) and laboratory tests (RAST and total IgE count) for the presence of atopy. Clinical manifestations (allergic rhinitis, asthma) and intense positive prick tests and RAST with an increase in total IgE count were found in 13 patients (22%). This frequency was significantly higher than that found in the normal population in our area (11.9%; p = 0.0212). These patients had a significantly higher incidence of vitiligo in their families (76.9 vs. 29.7% of the non-atopic; p less than 0.025), an earlier onset (14.1 vs. 24 years of the nonatopic) and a rapid worsening of the disease. PMID- 1884857 TI - Long-term administration of highly purified eicosapentaenoic acid provides improvement of psoriasis. AB - Nine patients with chronic stable psoriasis (4 males and 5 females) were entered in this trial. Eicosapentaenoic acid (EPA) ethylester (90% pure) without docosahexaenoic acid (DHA) in gelatin-coated capsules at a daily dose of 3.6 g was administered to 9 patients for 3 months, 7 patients for 6 months and 6 patients for 12 months. The clinical changes of skin lesions of the patients with 12 months of treatment were as follows: marked improvement 1, improvement 3, relative improvement 1, no change 1. A clinical improvement of skin lesions was first observed 2-3 months after EPA treatment. The supplementation of highly purified EPA caused a significant increase in the content of plasma EPA and docosapentaenoic acid without affecting that of arachidonic acid (AA) and DHA. EPA decreased the production of leukotriene B4 (LTB4) and increased the formation of leukotriene B5 (LTB5) and 5-hydroxyeicosapentaenoic acid significantly in A23187-stimulated neutrophils. The LTB5/LTB4 ratio positively correlated with the plasma EPA/AA ratio and was directionally related to the clinical score, although the directional data were not statistically significant. We could not observe any side effects of EPA over 1 year. Although its effects are modest, it is nontoxic and its favorable effect appears to continue for the duration of its usage, indicating that EPA could be beneficial for the long-term treatment of psoriasis. PMID- 1884858 TI - Solar urticaria and disturbed metabolism of porphyrins. AB - We report on a case of solar urticaria with elevated protoporphyrin in the stool. No other evidence for an erythropoietic protoporphyria could be found. PMID- 1884859 TI - Follicular impetigo as presenting sign of systemic lupus erythematosus. AB - A patient with an unusual form of follicular impetigo, who later developed classical systemic lupus erythematosus (SLE) is described. When she had pyoderma, direct immunofluorescence and serology already suggested a connective tissue disease. Pyoderma could have been the presenting manifestation of SLE. PMID- 1884860 TI - Metastatic squamous cell carcinoma resembling angiosarcoma complicating dystrophic epidermolysis bullosa. AB - We report a patient with generalized recessive dystrophic epidermolysis bullosa (RDEB) who developed 3 squamous cell carcinomas. The tumours appeared simultaneously at acral sites on both upper limbs and were poorly differentiated. Despite surgery and radiotherapy the patient died from metastatic disease within 6 months of presentation. This case highlights many of the typical features of this complication of RDEB, including the overall poor prognosis. Of particular interest was the histology of one of the tumours which caused diagnostic difficulties: haematoxylin and eosin staining suggested an angiosarcomatous pathology, but the use of immunocytochemistry proved that the tumour was a squamous cell carcinoma in origin. PMID- 1884861 TI - Nodular prurigo associated with Hodgkin's disease. AB - We report a case of prurigo nodularis of Hyde as the presenting sign of Hodgkin's disease in a 22-year-old girl. Though pruritus is a common symptom of Hodgkin's disease, prurigo nodularis has rarely been reported as a Hodgkin's symptom. PMID- 1884862 TI - Loose anagen hair in a child with Noonan's syndrome. AB - We report on a 4 1/2-year-old girl affected by loose anagen hair and Noonan's syndrome. The girl had short, blond, easily pluckable hair that had never been cut. The trichogram showed an absolute prevalence of abnormally shaped anagen bulbs lacking inner and outer root sheaths. A scalp biopsy evidenced a marked cleft formation between fragmented inner root sheaths and irregularly shaped hair shafts. PMID- 1884863 TI - Dual publication and manipulation of the editorial process. PMID- 1884864 TI - Topical minoxidil in monilethrix. PMID- 1884865 TI - Homoeopathic preparations--severe adverse effects, unproven benefits. PMID- 1884866 TI - Restoration of decayed primary incisors using strip crowns. AB - Caries of the primary incisors is a common problem that can be arrested if recognized early enough. However, the arrested decay is unsightly. Celluloid 'strip' crown forms, used with composite resin, now allow the restoration of even the most badly decayed primary incisors. The authors describe this quick and efficient technique. PMID- 1884867 TI - Ethnicity, health and dental care--perspectives among British Asians: 1. AB - In some areas, Asian communities constitute a sizeable proportion of the population around a general dental practice, yet some have never been to a dentist in the whole of their lives. A significant number of others fail to visit a dentist regularly. This two-part article aims to clarify some of the issues relating to dental care of minority groups, with particular reference to Asian communities. An outline is given of some general and dental health issues which are of particular significance to dental practitioners, as they strive to provide continuous care to the whole population. Part 1 identifies dental health problems characteristic of British Asians, Part 2 will examine some of the barriers to care. PMID- 1884868 TI - Sugar in baby foods. AB - Dentists and other members of the dental team are well placed to advise mothers of young babies about protecting their children's dental health, and there is general agreement that sugar is the "arch criminal of dental caries". However, sugars are present in a surprising range of foods, and it can be difficult to plan a diet to avoid them. This article reports on the sugar content of baby foods and drinks, and makes some policy recommendations. PMID- 1884869 TI - Oral pyogenic granulomas. AB - Pyogenic granulomas are benign growth occurring in various oral mucosal sites. They are thought to be caused by tissue response to non-specific irritation. Surgical excision and removal of irritants are the usual treatments, and recurrence is rare. The exception is the 'pregnancy epulis', where excision should only be considered if there is incomplete regression following childbirth. PMID- 1884870 TI - Extra-oral traction. AB - In orthodontics, the two main uses of extra-oral forces are in distalizing upper teeth and providing anchorage in the treatment of Class I and Class II malocclusions. This article reviews the theoretical principles behind the use of headgear, outlines the types available, and identifies the most appropriate designs for particular clinical situations. Practical guidelines for managing headgear treatment are also given. PMID- 1884871 TI - Ethnicity, health and dental care--perspectives among British Asians: 2. AB - In some areas, Asian communities constitute a sizeable proportion of the population around a general dental practice, yet some have never been to a dentist in the whole of their lives. A significant number of others fail to visit a dentist regularly. This two-part article aims to clarify some of the issues relating to dental care of minority groups, with particular reference to Asian communities. part 1 identified dental health problems characteristic of British Asians, Part 2 now examines some of the barriers to care. PMID- 1884872 TI - The structure and function of oral mucosa. AB - Understanding of the functional morphology and biology of the oral mucosa has advanced in recent year, particularly in such areas as epithelial-mesenchymal interaction, fibroblast heterogeneity, extracellular matrix, migration factors and growth factors, and the importance of these areas in the development and maintenance of the oral mucosa is increasingly appreciated. This article reviews current knowledge. PMID- 1884873 TI - Composite resin as a means of improving the appearance of periodontally involved teeth. AB - Composite resin has become established not only as a material for restoring carious teeth, but also as a means of veneering discoloured or misshapen teeth. This case report describes how composite resin was used to improve the appearance of a tooth which had become unsightly as the result of a combination of gingival recession and attrition. This was done by veneering both the root surface and the cervical area of the crown. PMID- 1884874 TI - [Role of high density lipoproteins (HDL) in reverse cholesterol transport]. AB - The atheromatous risk is negatively correlated with the plasma concentration of HDL cholesterol. This might be due to the role of HDL in the reverse cholesterol transport. In the first stage, free cholesterol molecules from peripheral cells are taken up by HDL through a receptor-dependent mechanism. In HDL, the esterification of cholesterol is catalysed by the lecithin: cholesterol acyl transferase. The progressive accumulation of cholesterol esters leads to the formation of HDL2. Through the action of cholesterol ester transfer protein, HDL2 become enriched in triglycerides and transfer cholesterol esters to LDL. Finally, cholesterol may be taken up by the liver through two routes which are: the receptor-mediated LDL endocytosis and the direct uptake of cholesterol esters which occurs during the degradation of HDL2 by hepatic lipase. PMID- 1884875 TI - Insulin sensitivity in zinc-depleted rats: assessment with the euglycaemic hyperinsulinic clamp technique. AB - The present knowledge about zinc deficiency and insulin-sensitivity is not yet established. Using three groups of rats fed zinc-depleted diet (ZD) zinc adequate diets, either Pair Fed or ad libitum for a six weeks period, we measured the glucose turn over by the euglycaemic hyperinsulinaemic clamp technique coupled with tritiated glucose as tracer. The basal hepatic glucose production (HGP) and insulinaemia were lower in zinc-depleted rats. At a low rate of insulin infusion (0.6 mU/min/rat) the zinc-depleted rats did not show any difference in hepatic insulin sensitivity compared with the pair-fed animals. At high level of insulin rate (3 mU/min/rat; 9 mU/min/rat), the zinc-depleted rats exhibited a lower glucose uptake compared to the two control groups (Pair-fed and Ad libitum animals). This peripheral insulin resistance is therefore related to a modification of insulin receptors, or post receptors events in zinc deficiency. PMID- 1884876 TI - The effect of bromhexine on albumin excretion in insulin dependent diabetes. AB - The effect of the mucolytic agent bromhexine, 72 mg daily for one month, on albumin excretion in insulin dependent diabetes was investigated in a double blind, randomised, cross-over, placebo-controlled study. Nine patients with normal albumin excretion [overnight albumin excretion rate 3.2 (2.1-8.8) micrograms/min.; mean (range)], six with microalbuminuria [36 (22-95) micrograms/min.] and six with macroalbuminuria [321 (201-1215) micrograms/min.] participated. Albumin excretion was similar after treatment with bromhexine and placebo in all 3 groups [normoalbuminurics 3.6 (1.7-13.5) versus 3.3 (1.9-13.2) micrograms/min.; microalbuminurics 40 (20-128) versus 37 (20-103); macroalbuminurics 396 (247-2160) versus 443 (292-2592)]. Excretion of beta 2 microglobulin and creatinine clearance were identical at the end of each treatment. Blood glucose control and blood pressure remained constant throughout the study in the 3 groups. We conclude that bromhexine 72 mg daily for 1 month had no effect on albumin excretion in IDDM patients with normal and pathological albuminuria. PMID- 1884877 TI - [Analysis of diabetes-related mortality in France (1970-1987) from multiple causes of death]. AB - The aim of this study was to analyse the characteristics and the mortality rate of diabetic patients, in France, between 1970 and 1987, as well as the association between diabetes and other pathologies at death. These results are based on both the underlying and the associated causes of death registered on the death certificate, in contrast to most studies which use only the underlying cause. In 1987, there were 16,790 deaths in France for which diabetes was mentioned on the death certificate (as the underlying cause in 38% of cases). There was a higher mortality in male diabetic subjects then in female, for all ages except over 75 years. Between 1970 and 1987, the mortality decreased for both sexes, except for the oldest age group. The death rate varied greatly between geographical regions. A particularly high mortality occurred in the Nord Pas-de-Calais, Lorraine and Alsace. Diabetes was significantly associated, at death, with other diseases and pathologies. The most frequent were vascular diseases (ischaemic heart disease, cerebral diseases and hypertension) and diseases of the genitourinary system. It if of note that 5% of the death certificates of these diabetic subjects indicated diabetic coma as a cause of death. PMID- 1884878 TI - Prostaglandin E2 affects both insulin secretion and peripheral insulin sensitivity. AB - The effect of prostaglandin E2 (PGE2) on plasma C-peptide (CP) level and peripheral insulin effectiveness was studied in twenty-five healthy volunteers. Plasma CP levels were studied in 14 volunteers (group C) during a three-hours PGE2 infusion. The same experiment was repeated a week later, with saline infusion. Plasma CP level were measured 15 minutes before the infusion, at the beginning of the experiment (0 min) as well as 15, 30, 60, 120 and 180 minutes after the start of the infusion. Peripheral insulin sensitivity was studied in vivo by means of the artificial endocrine pancreas (Biostator), using the euglycaemic hyperinsulinaemic clamp technique. The healthy volunteers underwent a three-hour experiment with saline (group A) or with saline and PGE2-10 micrograms/min during the third hour of clamping (group B). There was a significant decrease in plasma CP level at the 15 th and 30 th minute of PGE2 infusion in the subjects from group C (p less than 0.05). In the group A there was an increase of 14.2% in the amount of glucose infused during the third hour of clamping as compared to the second (2nd-9.673 +/- 1.680 mg/kg/min, 3rd-11.051 +/- 1.802 mg/kg/min). The amount of glucose infused in the subjects of group B remained the same in the course of clamping (2nd hour-7.938 +/- 2.180 mg/kg/min, 3rd hour-7.932 +/- 2.284 mg/kg/min). The difference in the dynamic changes of the amount of glucose infused between the two groups of volunteers (group A and group B) was significant (F = 5.68, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1884879 TI - Comparative study of semen in diabetic and healthy men. AB - This study examines the consequences of diabetes on male reproductive function. We have studied a group of 18 diabetics (15 type I, 3 type II) age 24 to 40 years (mean 34 +/- 5.3) with duration of diabetes from 2 to 30 years (mean 11.8 +/- 8.3). This group was compared to 20 semen donors. In diabetics higher sperm (p = 0.0063) and round cell (p = 0.031) concentrations/ml as well as a higher total spermatozoa count (p = 0.023) were observed. The percentage of abnormal sperms were also higher. None of the couples had consulted for sterility and they had a mean of 2 children. In this group of patients, diabetes was not a cause of subfertility. Specific spermiological alteration in diabetics might reflect a testicular damage secondary to their diabetes or disease. PMID- 1884880 TI - Effect of Miglitol (Bay m1099), a new alpha-glucosidase inhibitor, on glucose, insulin, C-peptide and GIP responses to an oral sucrose load in patients with post-prandial hypoglycaemic symptoms. AB - Sixteen patients suffering from symptoms suggestive of idiopathic reactive hypoglycaemia and reproducible during an oral glucose tolerance test when plasma glucose was less than or equal to 2.8 mM, were included in an acute, double-blind and cross-over study to test the efficacy of Miglitol (Bay m1099), a new alpha glucosidase inhibitor versus placebo. Patients were randomized to ingest 100 mg Miglitol or placebo together with a sucrose solution (45 g/m2 body surface), one week apart. During four hours, plasma glucose levels were continuously monitored and plasma insulin and gastric inhibitory polypeptide (GIP) levels were measured at 30-minute intervals; serum C-peptide concentration was determined at 0, 30, 60 minutes and then every hour. The post-load rise in plasma glucose was significantly blunted by Miglitol, as shown by the reduced plasma glucose peak, the diminished early (0-120 min) area under the glycaemic curve and the decreased rate of plasma glucose rise. Thereafter, plasma glucose nadir was significantly raised and rate of plasma glucose fall was slowed by Miglitol with a concomitant improvement in the hypoglycaemic index. Insulin secretion was dampened as indicated by parallel reduction of plasma insulin and serum C-peptide peaks; morever, early area under the insulin curve and total (0-240 min) area under the C-peptide curve were significantly reduced. Decrease of plasma GIP peak and total area under the GIP curve were also significant. During sucrose tolerance test with Miglitol, hypoglycaemic symptoms were significantly alleviated but intestinal side-effects were common. Blunting the insulin response to glucose directly by delaying glucose absorption and indirectly through reducing GIP secretion, may be a valuable therapeutic approach in reactive hypoglycemia; nevertheless, long-term study with Miglitol are needed, due to the poor intestinal tolerance of this drug in the present acute study. PMID- 1884881 TI - [Lack of benefit from the intermittent administration of insulin in treatment using subcutaneous perfusion pump in type 1 diabetes]. AB - Our study is based on two constatations: 1) Hyperinsulinaemia, a possible atherogenic factor, is frequent under continuous subcutaneous insulin infusion. 2) Pulsatile intravenous insulin delivery improve the insulin's hypoglycaemic activity. To test if equivalent metabolic control can be obtained with a reduced intermittent subcutaneous infused insulin dose, we compared nocturnal metabolic control of 8 c-peptide negative type 1 diabetic patients under three experimental conditions: Continuous usual dose test (1.0 +/- 0.1 u/h); Intermittent half dose test (1.0 +/- 0.1 u/h, 30 min/h); Continuous half dose test (0.5 +/- 0.05 u/h) Five parameters were monitored: blood glucose, plasma free insulin and beta hydroxy-butyrate, free fatty acid and glycerol plasma level. No significant differences were found between intermittent and continuous half-dose tests. We conclude that, in our experimental conditions, intermittent subcutaneous insulin infusion does not reduce the metabolic degradation induced by insulin dose reduction. PMID- 1884882 TI - Apolipoprotein levels in non-insulin-dependent diabetes mellitus with clinical macroangiopathy. AB - To elucidate the changes of serum apolipoproteins as possible atherogenic factors in non-insulin-dependent diabetes mellitus (NIDDM), comparison was made between 47 NIDDM patients with clinical macroangiopathy (coronary heart disease and/or cerebral infarction) and 47 NIDDM patients without clinical macroangiopathy individually matched for age, sex, body mass index, glycemic control, mode of therapy, and blood pressure. Serum total cholesterol (223 +/- 63 mg/dl, mean +/- SD) and triglyceride (160 +/- 72 mg/dl) levels in NIDDM with clinical macroangiopathy were significantly higher than those (198 +/- 44 and 126 +/- 78 mg/dl) in control NIDDM. Apolipoprotein AII (apo AII) (28.8 +/- 6.9 mg/dl) in NIDDM with clinical macroangiopathy was significantly lower than that (31.4 +/- 5.5 mg/dl) in control NIDDM, and apo B (147 +/- 48 mg/dl) and apo CIII (13.1 +/- 5.9 mg/dl) in NIDDM with clinical macroangiopathy was significantly higher than that (113 +/- 35 and 10.8 +/- 4.7 mg/dl) in control NIDDM, respectively. There were no significant differences in apo AI, CII, and E levels. The ratio of HDL cholesterol to apo AI (0.36 +/- 0.08) and total cholesterol to apo B (1.6 +/- 0.3) in NIDDM with clinical macroangiopathy was significantly lower than that (0.40 +/- 0.09 and 1.8 +/- 0.4) in control NIDDM. These results suggest that abnormality of lipid metabolism is more significant in NIDDM with clinical macroangiopathy than in NIDDM without clinical macroangiopathy, and is more pronounced in women than in men. PMID- 1884883 TI - [Renal tolerance during administration of iodinated contrast media in diabetic patients]. PMID- 1884884 TI - Serum lipoproteins and cholesterol metabolism in two hypercholesterolaemic rabbit models. AB - Serum lipoproteins and key hepatic and intestinal enzymes regulating cholesterol synthesis, esterification and catabolism, namely 3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase, acyl coenzyme A: cholesterol-o-acyltransferase (ACAT) and cholesterol 7 alpha-hydroxylase respectively, were compared in two hypercholesterolaemic rabbit models - the cholesterol-fed animal and the hypercholesterolaemic diabetic animal. Hypercholesterolaemia in the cholesterol fed animals was reflected in the VLDL and LDL fractions, whereas VLDL and HDL2 cholesterol levels were elevated in the diabetic animals. The lipoproteins of the cholesterol-fed animals were enriched with cholesterol but the lipoprotein fractions in the diabetic animals were enriched with triacylglycerol. While hepatic HMGCoA reductase activity was significantly reduced in both groups, the activities of hepatic ACAT and cholesterol 7 alpha-hydroxylase were significantly increased in the cholesterol-fed animals and significantly reduced in the diabetic animals compared with controls. In the intestine, the activity of HMGCoA reductase was increased and ACAT reduced in the diabetic animals. By contrast, in the cholesterol-fed group. HMGCoA reductase activity was lower and ACAT activity was higher in comparison with the control group. These differences in lipoproteins and cellular cholesterol metabolism between the hypercholesterolaemic rabbit models may explain the differences in susceptibility to atherosclerosis, previously reported in these two animal models. PMID- 1884885 TI - In vivo metabolic action of insulin-like growth factor I in adult rats. AB - The acute metabolic actions of insulin-like growth factor I were studied in anaesthetized adult rats and its potency was compared to that of insulin. Following an i.v. bolus injection of insulin-like growth factor I a dose dependent decrease of blood glucose and serum non-esterified fatty acid concentrations was noted with a potency of about 2% that of insulin. Stimulation of total body glucose disposal during euglycaemic clamping required approximately 50 times higher insulin-like growth factor I serum concentrations to achieve an identical half-maximal response. A similar difference in potency was observed for the stimulatory action on 2-deoxyglucose uptake and on glycogen formation in skeletal muscle. Lipogenesis in epididymal fat pads was increased dose dependently by both hormones requiring approximately 30 times higher half maximally effective serum concentrations of insulin-like growth factor I. These data demonstrate that insulin-like growth factor I exerted acute insulin-like metabolic actions in vivo with low potency. These effects were probably mediated via insulin receptors. A preferential stimulation of glucose metabolism in skeletal muscle was not observed. PMID- 1884886 TI - Heat shock protein induction in rat pancreatic islets by recombinant human interleukin 1 beta. AB - Interleukin 1 beta, potentiated by tumour necrosis factor alpha, is cytotoxic to pancreatic Beta cells in vitro. We have hypothesized that interleukin 1 beta induces oxygen free radicals in Beta cells. Since cytotoxicity induced by free radicals and by heat may activate the same cellular repair mechanism (the heat shock response), the aim of this study was to investigate the pattern of protein synthesis in isolated islets after exposure to interleukin 1 beta (150 pg/ml, 24 h), tumour necrosis factor alpha (50 ng/ml, 24 h) heat shock (43 degrees C, 30 min) and H2O2 (0.1 mmol/l, 20 min). By polyacrylamide gel electrophoresis, autoradiography, Western-blot analysis and partial peptide mapping of 35S methionine labelled islets, interleukin 1 beta was found to induce a 73 kilodalton protein belonging to the heat shock protein family heat shock protein 70, a heat shock protein 90, and haem oxygenase. A minor induction of heat shock protein 73 and haem oxygenase was seen after H2O2. Interleukin 1 beta did not induce heat shock proteins in rat thyroid cells, rat mesangial cells or in human monocytes. Tumour necrosis factor alpha did not induce selective protein synthesis. Pre-exposure of islets to heat, tumour necrosis factor alpha, or H2O2 did not prevent the impairment of glucose-stimulated insulin release seen after 24 h of interleukin 1 beta exposure. The data are compatible with free radical induction by interleukin 1 beta. However, the heat shock response is not specific for oxidative injury, and previous studies have shown discrepant effects as to a protective effect of free radical scavengers against interleukin 1 beta-mediated beta-cytotoxicity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1884887 TI - Effect of improved metabolic control on loss of kidney function in type 1 (insulin-dependent) diabetic patients: an update of the Steno studies. AB - We re-examined 69 of the 70 patients entering the two independent Steno Studies of effects of improved metabolic control on progression of late diabetic complications. They were analysed according to an intent to treat after follow-up for 8 years (Steno Study 1) and 5 years (Steno Study 2). The glycaemic control had improved in the insulin infusion group compared with the conventional treatment group (mean HbA1c) by 2.0 +/- 0.6% vs 0.7 +/- 1.2 in Steno Study 1 and by 1.8 +/- 1.2% vs 0.4 +/- 1.3 (p less than 0.01) in Steno Study 2. In the insulin infusion groups three patients had died during episodes of ketoacidosis. These were not caused by malfunction of the insulin infusion pumps. In the conventional treatment groups, three patients suffered five cardiovascular events causing two deaths. From the sixth month of Steno Study 1 the annual change of the glomerular filtration rate was -3.7 (-5.4 to -2.0) ml.min-1.1.73 m-2 vs -1.0 (-2.1 to -0.1) (conventional vs insulin infusion group, mean (95% confidence interval, p less than 0.01]. The change in urinary albumin excretion was associated with the glycaemic control (n = 69, r = 0.49, p less than 0.0002). No progression was observed among 32 patients with low range microalbuminuria (30 to 99 mg/24 h).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1884888 TI - Disturbed handling of ascorbic acid in diabetic patients with and without microangiopathy during high dose ascorbate supplementation. AB - Abnormalities of ascorbic acid metabolism have been reported in experimentally induced diabetes and in diabetic patients. Ascorbate is a powerful antioxidant, a cofactor in collagen biosynthesis, and affects platelet activation, prostaglandin synthesis and the polyol pathway. This suggests a possible close interrelationship between ascorbic acid metabolism and pathways known to be influenced by diabetes. We determined serum ascorbic acid and its metabolite, dehydroascorbic acid, as indices of antioxidant status, and the ratio, dehydroascorbate/ascorbate, as an index of oxidative stress, in 20 matched diabetic patients with and 20 without microangiopathy and in 22 age-matched control subjects. Each study subject then took ascorbic acid, 1 g daily orally, for six weeks with repeat measurements taken at three and six weeks. At baseline, patients with microangiopathy had lower ascorbic acid concentrations than those without microangiopathy and control subjects (42.1 +/- 19.3 vs 55.6 +/- 20.0, p less than 0.01, vs 82.9 +/- 30.9 mumol/l, p less than 0.001) and elevated dehydroascorbate/ascorbate ratios (0.87 +/- 0.46 vs 0.61 +/- 0.26, p less than 0.01, vs 0.38 +/- 0.14, p less than 0.001). At three weeks, ascorbate concentrations rose in all groups (p less than 0.0001) and was maintained in control subjects (151.5 +/- 56.3 mumol/l), but fell in both diabetic groups by six weeks (p less than 0.01). Dehydroascorbate/ascorbate ratios fell in all groups at three weeks (p less than 0.0001) but rose again in the diabetic groups by six weeks (p less than 0.001) and was unchanged in the control subjects. Dehydroascorbate concentrations rose significantly from baseline in all groups by six weeks of ascorbic acid supplementation (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1884889 TI - The Swedish childhood diabetes study. Vaccinations and infections as risk determinants for diabetes in childhood. AB - In a nationwide incident case referent study we have evaluated vaccinations, early and recent infections and the use of medicines as possible risk determinants for Type 1 (insulin-dependent) diabetes mellitus in childhood. A total of 339 recently onset diabetic and 528 referent children, age 0-14 years, were included. Information about infections was collected from a mailed questionnaire and about vaccinations from childhood health care centres and schools. When vaccinations were considered as possible risk factors for diabetes, a significant decrease in relative risk estimated as odds ratio (OR) was noted for measles vaccination (OR = 0.69; 95% confidence limits 0.48-0.98). For vaccination against tuberculosis, smallpox, tetanus, whooping cough, rubella and mumps no significant effect on OR for diabetes was found. The odds ratios for Type 1 diabetes for children exposed to 0.1-2 or over 2 infections during the last year before diagnosis of diabetes revealed a linear increase (OR = 1.0, 1.96 and 2.55 for 0, 1-2 and over 2 infections, respectively). The trend was still significant when standardized for possible confounders such as age and sex of the children, maternal age and education and intake of antibiotics and analgetics. In conclusion, a protective effect of measles vaccination for Type 1 diabetes in childhood is indicated as well as a possible causal relationship between the onset of the disease and the total load of recent infections. PMID- 1884890 TI - Autonomic neuropathy, QT interval lengthening, and unexpected deaths in male diabetic patients. AB - QT intervals were measured over RR intervals ranging from 500 ms to 1000 ms in 13 normal male subjects, 13 male diabetic subjects without and 13 with autonomic neuropathy. There was a close linear relationship between QT and RR in all subjects. The slope of the regression line was significantly greater in the autonomic neuropathy group than the normal group. Thirty-two male diabetic subjects with varying degrees of autonomic dysfunction had repeat QT measurements 3 (range 2-6) years later. QT and QTC lengthened significantly at the second visit, unrelated to age or time between recordings, but which corresponded with changes in autonomic function. Of 71 male diabetic subjects under 60 years followed for 3 years, 13 had died, 8 unexpectedly. Of those with autonomic neuropathy. QT and QTC were significantly longer in those who subsequently died, despite similar ages and duration of diabetes. We conclude that QT/RR interval relationships are altered in diabetic autonomic neuropathy, and that changes in QT length with time parallel changes in autonomic function. There may be an association between QT interval prolongation and the risk of dying unexpectedly in diabetic autonomic neuropathy. PMID- 1884891 TI - Autoantibodies and genetic factors associated with the development of type 1 (insulin-dependent) diabetes mellitus in first degree relatives of diabetic patients. AB - Factors associated with diabetes onset were analysed for their predictive value in 708 first-degree relatives of Type 1 (insulin-dependent) diabetic patients including 374 parents and 308 siblings of Type 1 diabetic patients. Relatives were prospectively followed for 2,304 subject years with blood samples for specific autoantibody evaluation. Islet cell cytoplasmic autoantibody titres were quantified in Juvenile Diabetes Foundation units with a threshold of positivity of 5 units. Insulin autoantibodies were determined using Tyr-A14 iodinated human insulin. HLA typing was performed in 92% of the relatives. During the time of study, 17 of 646 (2.6%) relatives showed islet cell antibodies. During follow-up, eight relatives developed diabetes, including six with high islet cell antibody titre. Taking titres above 20 units increased the positive predictive value from 35% to 75% whereas the presence of insulin autoantibodies did not increase the positive predictive value for the disease. Analysis of metabolic profiles months before the onset of diabetes by either oral or intravenous glucose loads, indicated a considerable level of heterogeneity with relatives with a high islet cell antibody titre who rapidly developed insulin-dependent diabetes, whereas other remained insulin-independent during the same observation period despite comparable titres. This study clearly indicates that initial islet cell antibody titre is not sufficient to predict individual outcome. Follow-up samples are clearly needed to monitor progression of the disease. Few relatives with persistent immunologic positivity progress to clinical Type 1 diabetes, suggesting that non-progressive and sub-clinical Beta-cell dysfunction is common.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1884893 TI - Poor predicting values in obtaining non-insulin requiring remission using proinsulin/C-peptide ratios. PMID- 1884892 TI - Non-esterified fatty acids do not contribute to insulin resistance in persons at increased risk of developing type 2 (non-insulin-dependent) diabetes mellitus. AB - The mechanisms underlying insulin resistance in Type 2 (non-insulin-dependent) diabetes mellitus are not fully understood. An enhanced lipid/non-esterified fatty acid oxidation could provide an explanation. To test this hypothesis we examined the relationship between glucose and lipid metabolism in 44 first-degree relatives (28 glucose-tolerant and 16 glucose-intolerant) of Type 2 diabetic patients and in 18 healthy control subjects. Total body glucose disposal was impaired among both glucose-tolerant and glucose-intolerant relatives compared with control subjects (36.3 +/- 3.8 and 30.4 +/- 2.7 vs 47.7 +/- 3.4 mumol.kgLBM 1. min-1; p less than 0.05). The impairment in glucose disposal among the relatives was primarily accounted for by impaired non-oxidative glucose metabolism (14.8 +/- 3.0 and 12.5 +/- 1.8 vs 25.3 +/- 3.1 mumol.kgLBM-1.min-1; p less than 0.05). Plasma non-esterified fatty acid concentrations were similar in both glucose-tolerant and glucose-intolerant relatives and control subjects (646 +/- 36, 649 +/- 43 and 615 +/- 41 mumol/l) and showed the same degree of suppression by insulin (99 +/- 8, 86 +/- 7 and 84 +/- 9 mumol/l). Basal lipid oxidation was similar in all groups (1.29 +/- 0.09, 1.52 +/- 0.13 and 1.49 +/- 0.21 mumol.kgLBM-1. min-1). Furthermore, insulin suppressed lipid oxidation to the same degree in glucose-tolerant, glucose-intolerant relatives and control subjects (0.65 +/- 0.13, 0.88 +/- 0.15 and 0.59 +/- 0.09 mumol.kgLBM-1.min 1).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1884894 TI - Repeatability of the oral glucose tolerance test for the diagnosis of impaired glucose tolerance and diabetes mellitus. PMID- 1884895 TI - Proinsulin conversion intermediates: a possible source of confusion. PMID- 1884896 TI - Influence of severe diabetes mellitus early in pregnancy in the rat: effects on insulin sensitivity and insulin secretion in the offspring. AB - We studied the influence of severe diabetes early in pregnancy on insulin sensitivity and insulin secretion in the offspring. Diabetes (blood glucose greater than 20 mmol/l) was induced in female Sprague-Dawley rats before mating. Diabetic dams were insulin treated during the second half of pregnancy (mean blood glucose 10.6 mmol/l). The offspring were reared by foster mothers. Offspring of both sexes were insulin resistant at four and seven months of age as evidenced by normal glucose tolerance after glucose (2 g/kg body weight intraperitoneally) concomitant with higher than normal rises in insulin levels. Regardless of fetal environment the male rats had higher glucose and insulin levels than the female rats. Insulin responses to glucose (27 mmol/l) in vitro in perfused pancreases were not increased by maternal diabetes, male gender or higher age. Conversely responses to 3-isobutyl-1-methylxanthine (1.0 mmol/l) were enhanced by all three conditions. The pancreatic content of insulin was only marginally affected by maternal diabetes. We conclude that severe diabetes during early pregnancy affects glucose homeostasis in the offspring primarily by diminishing insulin sensitivity and that susceptibility to this effect is not sex or age-dependent. PMID- 1884898 TI - Five-year follow-up of islet cell antibodies in type 2 (non-insulin-dependent) diabetes mellitus. AB - The aim was to study the frequency and appearance of cytoplasmic islet cell antibodies in relation to impairment of insulin secretory capacity and some clinical characteristics in a representative group of middle-aged (45-64 years) patients with Type 2 (non-insulin-dependent) diabetes mellitus (70 male, 63 female) at the time of diagnosis and at five-year follow-up. Non-diabetic control subjects (62 male, 82 female) were similarly examined at five-year intervals. At the baseline five out of 133 (3.8%) diabetic patients were positive for conventional and four (3.0%) for complement-fixing islet cell antibodies. Ten patients had become positive by the second screening for conventional antibodies and six for complement-fixing antibodies, but none showed negative conversion. Two non-diabetic subjects (1.5%) became antibody positive during the follow-up. Insulin treatment was started during the follow-up for four out of 15 (27%) conventional antibody positive and for one out of 121 (0.8%) antibody negative diabetic patients (p = 0.001). The sensitivity of the positive conventional and complement-fixing antibody for identifying patients who developed an impairment of insulin secretory capacity (post-glucagon C-peptide less than or equal to 0.60 nmol/l at 5-year) was 75%. The respective specificity was 90% and the positive predictive values were highest in the case of high positivity (50%). The negative predictive value of antibody positivity was close to 100%. In conclusion, islet cell antibody positivity in patients classified as Type 2 was persistent during the follow-up and predicted the future development of insulin deficiency especially in those patients with high or increasing antibody titres. PMID- 1884897 TI - Functional and morphological differentiation of fetal porcine islet-like cell clusters after transplantation into nude mice. AB - By using a previously described culture technique for the midgestational fetal porcine pancreas, islet-like cell clusters with a Beta-cell frequency of approximately 5% have been produced in large numbers. These islet-like cell clusters were transplanted beneath the kidney capsule to either normoglycaemic or alloxan-treated nude mice. The grafts consistently failed to cure the alloxan treated mice immediately after implantation, however, normoglycaemia was restored in a majority of the mice within 2 months after transplantation and in all animals after 4 and 6 months. Indeed, the insulin released from the transplanted fetal Beta cells was able to normalize the serum glucose concentration at porcine levels (4-5 mmol/l) rather than at the level maintained in mice (8-10 mmol/l). In the cured mice there was a normal secretory response to glucose in the grafts as evidenced by normal glucose profiles during intravenous glucose tolerance test and a biphasic insulin response to high glucose when perfusing the graft bearing kidney. On the other hand, in the normoglycaemic animals the second phase faded before the glucose stimulus had been withdrawn. Two months after transplantation the endocrine cells were arranged so that the endocrine non-Beta cells were randomly scattered among a majority of Beta cells. The cell replication of the Beta cells, measured by 3H-thymidine incorporation, was within the lower range of that seen in the native islets of adult mice. No major differences between the controls and the alloxan-treated animals were observed in this respect. Cultured islet-like cell clusters had high rates of glucose utilization, paralleled by low rates of glucose oxidation, compared with adult mouse islets.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1884899 TI - Modulation of hepatic glucose production by non-esterified fatty acids in type 2 (non-insulin-dependent) diabetes mellitus. AB - To study the effect of changes in plasma non-esterified fatty acid concentration on suppression of hepatic glucose production by insulin eight Type 2 (non-insulin dependent) diabetic patients participated in three euglycaemic, hyperinsulinaemic (108pmol.m2-1.min-1) clamp studies combined with indirect calorimetry and infusion of [3-3H]-glucose and [1-14C]palmitate; (1) a control experiment with infusion of NaCl 154 mmol/l, (2) heparin was infused together with insulin, and (3) an antilipolytic agent, Acipimox, was administered at the beginning of the experiment. Six healthy volunteers participated in the control experiment. Plasma non-esterified fatty acid concentrations during the insulin clamp were in diabetic patients: (1) 151 +/- 36 mumol/l, (2) 949 +/- 178 mumol/l, and (3) 65 +/ 9 mumol/l; in healthy control subjects 93 +/- 13 mumol/l. Non-esterified fatty acid transport rate, oxidation and non-oxidative metabolism were significantly higher during the heparin than during the Acipimox experiment (p less than 0.001). Suppression of hepatic glucose production by insulin was impaired in the diabetic compared to control subjects (255 +/- 42 vs 51 +/- 29 mumol/min, p less than 0.01). Infusion of heparin did not affect the suppression of hepatic glucose production by insulin (231 +/- 49 mumol/min), whereas Acipimox significantly enhanced the suppression (21 +/- 53 mumol/min, p less than 0.001 vs 154 mmol/l NaCl experiment). We conclude that insulin-mediated suppression of hepatic glucose production is not affected by increased non-esterified fatty acid availability. In contrast, decreased non-esterified fatty acid availability enhances the suppression of hepatic glucose production by insulin. PMID- 1884900 TI - Hyperinsulinaemia: the key feature of a cardiovascular and metabolic syndrome. AB - In a population-based survey of 2,930 subjects, prevalence rates for obesity, Type 2 (non-insulin-dependent) diabetes mellitus, impaired glucose tolerance, hypertension, hypertriglyceridaemia, and hypercholesterolaemia were 54.3, 9.3, 11.1, 9.8, 10.3 and 9.2%, respectively. The prevalence, however, of each of these conditions in its isolated form (free of the other five) was 29.0% for obesity, 1.3% for Type 2 diabetes, 1.8% for impaired glucose tolerance, 1.5% for hypertension, 1.0% for hypertriglyceridaemia, and 1.7% for hypercholesterolaemia. Two-by-two associations were even rarer. The large differences in prevalence between isolated and mixed forms indicate a major overlap among the six disorders in multiple combinations. In the isolated form, each condition was characterized by hyperinsulinaemia (both fasting and 2 h after oral glucose), suggesting the presence of insulin resistance. In addition, in any isolated condition most of the variables categorising other members of the sextet were still significantly altered in comparison with 1,049 normal subjects. In the whole of the subjects who presented with one or another disorder (1,881 of 2,930 or 64%), marked fasting and post-glucose hyperinsulinaemia was associated with higher body mass index, waist:hip ratio, fasting and post-glucose glycaemia, systolic and diastolic blood pressure, serum triglycerides and total cholesterol levels, and with lower HDL-cholesterol concentrations (all p less than 0.001). We conclude that (1) insulin sensitivity, glucose tolerance, blood pressure, body fat mass and distribution, and serum lipids are a network of mutually interrelated functions; and (2) an insulin resistance syndrome underlies each and all of the six disorders carrying an increased risk of coronary artery disease. PMID- 1884901 TI - Renal and splanchnic exchange of human biosynthetic C-peptide in type 1 (insulin dependent) diabetes mellitus. AB - Biosynthetic human C-peptide or NaCl (154 mmol.l-1) was given intravenously to 13 Type 1 (insulin-dependent) diabetic patients to determine the renal and splanchnic exchange of C-peptide. Catheters were inserted percutaneously into an artery and a renal and hepatic vein. Infusions of C-peptide were given for 60 min at two dose levels (5 and 30 pmol.kg-1.min-1). Insulin was infused throughout the study (0.5 mU.kg-1.min-1) and plasma glucose was kept constant by a variable glucose infusion. The regional blood flows were measured by indicator dilution techniques. In 11 of the 13 patients basal C-peptide levels were not detectable. The arterial steady-state C-peptide concentration was 0.81 +/- 0.10 nmol.l-1 and 2.33 +/- 0.30 nmol.l-1 at the low and high rate infusions, respectively. Renal uptake was 124 +/- 18 pmol.min-1 at the low infusion corresponding to 39% of the infused amount. At the higher dose C-peptide infusion renal uptake increased to 155 +/- 21 pmol.min-1 (p less than 0.05). Urinary excretion of C-peptide was 7 +/ 2 pmol.min-1 at the low dose infusion and increased to 34 +/- 6 pmol.min-1 at the high dose infusion (p less than 0.01). The proportions of infused amount excreted were fairly constant and between 2% and 3%. No net exchange of C-peptide was found across the splanchnic vascular bed. The rate of glucose infusion had to be increased by 35% during the low dose C-peptide, but not during NaCl infusion in order to maintain a constant plasma glucose concentration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1884902 TI - Follow-up of cyclosporin A treatment in type 1 (insulin-dependent) diabetes mellitus: lack of long-term effects. AB - In the Canadian/European randomized controlled study on cyclosporin A (CsA) in recent onset Type 1 (insulin-dependent) diabetes, treatment with the immunosuppressive drug had increased and maintained Beta-cell function and clinical remission during the first 12 months. Following discontinuation of the study drug and double-blinding after a mean of 13.8 months former CsA patients doubled the daily insulin dose within 6 months reaching the level of former placebo patients. The difference in Beta-cell function between the two groups was also lost. Metabolic control (HbA1c) was transiently worse in the former CsA group. Adverse effects of cyclosporin A on systolic blood pressure, haemoglobin levels, serum potassium and creatinine levels also remitted during that time. We conclude that treatment with cyclosporin A for a mean of 13.8 months had no long lasting effect on the course of Type 1 diabetes persisting beyond drug discontinuation. PMID- 1884903 TI - Localisation of islet amyloid polypeptide and its carboxy terminal flanking peptide in islets of diabetic man and monkey. AB - Islet amyloid polypeptide is a normal constituent of islet Beta cells and is derived from a larger precursor by removal of flanking peptides at the carboxy (C) and amino (N) terminals. The role of these flanking peptides in the formation of amyloid in Type 2 (non-insulin-dependent) diabetes mellitus and in insulinomas is unknown. The C-terminal flanking peptide of islet amyloid polypeptide was localised by immunocytochemistry in human and monkey pancreatic islets from Type 2 diabetic and non-diabetic individuals by use of specific polyclonal antisera. Immunoreactivity for the C-terminal peptide was found in insulin-containing cells in both diabetic and non-diabetic tissue: no antibody binding was detected in islet amyloid of Type 2 diabetic man or of monkeys although a positive reaction occurred with antisera for islet amyloid polypeptide. The C-terminal peptide was localised by immunogold electron microscopy in the insulin granules in both diabetic and non-diabetic individuals but, unlike islet amyloid polypeptide, was not detected in lysosomes. The absence of immunoreactivity for the C-terminal peptide in amyloid suggests that incomplete cleavage of this flanking peptide from islet amyloid polypeptide is not a factor in the formation of islet amyloid. PMID- 1884905 TI - Family cell lines available for diabetes research. PMID- 1884904 TI - Increased blood pressure and erythrocyte sodium/lithium countertransport activity are not inherited in diabetic nephropathy. PMID- 1884906 TI - Concerns in toxicology--a personal perspective. PMID- 1884907 TI - The effects of soman poisoning in combination with hypovolemic shock. AB - Hemorrhage is a cause of death in both combat and civilian injuries. The specific objectives of this research were: (1) to determine the pathophysiologic effects of combined injuries from sublethal amounts of an organophosphate (soman) along with hypovolemic shock, and (2) to determine the efficacy of atropine sulfate and pralidoxime (2-PAM) therapy for organophosphate poisoning when combined injuries occur. Four groups of six beagle dogs/group were used: Group V/H, vehicle administration followed by hemorrhage; Group S/H, soman administration followed by hemorrhage; Group S/A/H, soman followed by antidote (atropine and 2-PAM) and then hemorrhage; and Group S, soman only. Acetylcholinesterase (AChE) activity, hemodynamic parameters, regional blood flow, plasma enzyme, and hematological changes were monitored. Soman rapidly decreased AChE activity in RBCs, plasma, and brain tissue. Treatment with atropine and 2-PAM resulted in only slight reactivation of AChE; they helped maintain blood gases, cortisol, plasma enzymes, inspiratory volume, and blood pressure nearer baseline values. The effects of combined injuries appear to be greater than those of either injury alone. This was indicated by increased plasma lactate, plasma enzymes indicative of tissue damage (aspartate amine transferase and creatine kinase), and increased lethality in dogs subjected to both soman and hemorrhage (5/12 died). All dogs subjected to only one insult survived the 6-hr experiment. PMID- 1884908 TI - The prenatal inhalation toxicity of acrylic acid in rats. AB - Pregnant Sprague-Dawley rats (5 per groups) were exposed in a pretest to 0, 225, and 450 ppm acrylic acid (AA) and in a main study (30 per group) to 0, 40, 120, and 360 ppm acrylic acid. Exposures were for 6 hr/day, during Days 6 to 15 of gestation (period of organogenesis), with further observation up to Day 20 after mating. Maternal toxicity occurred in animals exposed at 450 and 225 ppm in the pretest. At 360 ppm in the main study maternal toxicity consisted of sensory irritation (discharge from the eyes, snout wiping, and restless behavior) with significant reductions in body weight (p less than 0.01), body weight gain (p less than 0.01), and food consumption (p less than 0.01) relative to that of chamber controls. Effects on body weight and body weight gain were dose-related and when corrected for uterus weight were significant in animals exposed to 120 ppm (p less than 0.01), with an effect on body weight gain also at 40 ppm (p less than 0.05), indicating a minimal maternal toxic effect. There were no signs of group-related trends or significant differences between groups in terms of numbers of preimplantation losses, live fetuses, or resorptions, and no signs of group-related differences in the incidences of abnormalities, variations, or retardations in the fetuses in terms of general appearance and the condition of the internal organs or the skeletons. It is concluded that under the experimental conditions of the main study acrylic acid vapor at concentrations between 40 and 360 ppm had no embryotoxic teratogenic effects on Sprague-Dawley rats. Maternal toxicity was minimal at 40 ppm, clearer at 120 ppm, and more pronounced at 360 ppm. PMID- 1884909 TI - Chronic toxicity studies with thiram in Wistar rats and beagle dogs. AB - Groups of 64 male and 64 female Wistar rats were given thiram at constant dietary doses of 0, 3, 30, and 300 ppm (0, 0.1, 1.2, and 11.6 mg/kg/day for males and 0, 0.1, 1.4, and 13.8 mg/kg/day for females) for 104 weeks. Eight males and eight females in each group were killed after Weeks 13, 26, and 52. For the dog study, four male and four female beagle dogs were alloted to each group and treated with the compound at 0, 0.4, 4, and 40 mg/kg/day for 104 weeks. The dogs in the 40 mg/kg/day group had severe toxic signs, including nausea or vomiting, salivation, and occasional clonic convulsion, and all were subjected to unscheduled necropsy before Day 203 of treatment. The dogs also had ophthalmological changes such as fundal hemorrhage, miosis, and desquamation of the retina which were consistent with the retinal lesions shown by histopathology. The rats of the high-dose group had retarded growth with a slightly decreased food intake. Anemia was evident in high-dose female rats and in middle- and high-dose dogs. Liver failure in male and female dogs and kidney damage in female dogs were detected in middle- and high-dose groups by blood biochemistry and/or histopathology. Regressive changes of the sciatic nerve accompanied by atrophy of the calf muscle were seen in female rats of the high-dose group but not in male rats. In high-dose rats, progression of myocardial lesions of the heart and chronic nephrosis of the kidney were depressed in males and females, respectively. Female rats of the middle- and high-dose groups had decreased occurrences of mammary fibroadenoma and decreased development of skin masses. PMID- 1884911 TI - The effects of potassium chromate and citrinin on rat renal membrane transport. AB - Both chromate and citrinin have been shown to produce acute renal damage. Although both substrates act on the proximal tubule in the rat, they affect different parts of that nephron segment. As with most nephrotoxicants, the mechanism(s) or subcellular target(s) for citrinin or chromate is unknown. The availability of methodology for isolation of functional membrane vesicles has afforded the opportunity to study the plasma membrane as a target for the effects of citrinin and chromate. Whether studied solely with in vitro conditions or after administration to the rat, chromate exhibited its primary action on the basolateral (BL) membrane vesicles. This was exhibited by a reduction in the p aminohippurate (PAH) overshoot. At both 3 and 16 hr after treatment (40 mg/kg, sc) there was a significant, but relatively modest, effect on glucose transport by brush border (BB) vesicles. Citrinin, when studied in vitro, inhibited PAH transport (BL vesicles), but had only equivocal effects on BB glucose transport. However, after pretreatment of the rats with citrinin (60 mg/kg, ip), both BL and BB membrane vesicle function was reduced markedly at 3 hr. By 16 hr, an overshoot had returned for both transport substrates, although the glucose overshoot was still significantly below control. These data demonstrate that both citrinin and chromate alter proximal tubular cell membrane function and do so relatively early after administration to the rat. This effect suggests that alteration of membrane function by these nephrotoxicants is an early, if not initiating, event in the production of acute tubular necrosis. PMID- 1884910 TI - The effects of ethylene dibromide on semen quality and fertility in the rabbit: evaluation of a model for human seminal characteristics. AB - Mature (12 months old) male New Zealand White rabbits (8-10/group) were dosed subcutaneously with ethylene dibromide (EDB) in corn oil (untreated and vehicle controls, 15, 30, or 45 mg/kg body wt/day for 5 days). Weekly semen samples (for 6 weeks preexposure, during treatment, and 12 weeks postdosing [pd]) were analyzed for sperm concentration, number, morphology, viability, and motion parameters (velocity, linearity, beat cross-frequency, amplitude of lateral head displacement (ALH), and circularity), and semen pH, osmolality, volume, fructose, citric acid, carnitine, protein, and acid phosphatase (AP). Male fertility was assessed preexposure and at 4 and 12 weeks pd by artificial insemination of three females/male/time point with one million motile sperm. The percentage pregnant females, litter size, fetal body weights, and structural development were assessed. In the 45 mg/kg dose group of males there was 30% mortality and liver damage in 43% of the survivors as evidenced by increased levels of serum enzymes. Also in this group, EDB produced significant decreases in sperm velocity, percentage motility, and ALH (up to 25% at various times pd). There were also dose-related decreases in semen pH (up to 2%) and total ejaculate volume (up to 23%, 15 and 30 mg/kg dose groups only). AP activities were significantly elevated (up to 116%) 2 weeks pd in the 45 mg/kg dose group. All other semen parameters evaluated were unaffected. Male fertility and fetal structural development were also unaffected. Of the seven semen parameters perturbed by EDB in humans (Schrader et al., 1988), four were also affected in the rabbit (sperm velocity, percentage motility, pH, and volume), whereas sperm number, viability, and morphology were not. Thus, some of the male reproductive effects of EDB in the human have been modelled in the rabbit, although the rabbit appears not to be as sensitive, since semen parameters were affected only at doses close to the LD50 (55 mg/kg). The present study (together with other published data) suggests that the rabbit appears to be a potential model for male reproductive toxicity in humans, warranting further evaluation. PMID- 1884912 TI - Glyphosate skin binding, absorption, residual tissue distribution, and skin decontamination. AB - Glyphosate is a broad-spectrum postemergence translocated herbicide. Its interactions with skin and potential systemic availability through percutaneous absorption was studied by skin binding, skin absorption, residual tissue distribution, and skin decontamination. Glyphosate in a final formulation (Roundup) undiluted and diluted with water 1:20 and 1:32, would not partition into powdered human stratum corneum (less than 1%). In vitro percutaneous absorption through human skin into human plasma as receptor fluid was no more than 2% over a concentration range of 0.5-154 micrograms/cm2 and a topical volume range of 0.014-0.14 ml/cm2. Disposition of glyphosate following iv administration of 93 and 9 micrograms doses to rhesus monkeys was mainly through urine excretion, 95 +/- 8 and 99 +/- 4% in 7 days, respectively. Percutaneous absorption in vivo in rhesus monkey was 0.8 +/- 0.6% for the low dose (25 micrograms/cm2) and 2.2 +/- 0.8% for the high dose (270 micrograms/cm2). No residual 14C was found in organs of the monkeys euthanized 7 days after the topical application. Washing the skin application site with soap and water removed 90 +/- 4% of applied dose, and washing with water only removed 84 +/- 3% of applied dose. Both soap and water and water only were equal in ability to remove glyphosate from skin over a 24 hr skin application period. About 50% of the initially applied dose could be recovered after 24 hr. Glyphosate is very soluble in water and insoluble in most organics (octanol/water log P = -1.70) and therefore not compatible with the lipid-laden stratum corneum.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1884913 TI - Developmental toxicity of inhaled methyl ethyl ketone in Swiss mice. AB - Methyl ethyl ketone (MEK) is a widely used industrial solvent to which there is considerable human exposure. To assess the potential for MEK to cause developmental toxicity in rodents, groups of Swiss (CD-1) mice were exposed to 0, 400, 1000, or 3000 ppm MEK vapors 7 hr/day on Days 6-15 of gestation. Groups consisted of about 30 bred females each. Exposure of pregnant mice to these concentrations of MEK did not result in overt maternal toxicity although there was a slight, treatment-related increase in relative liver weight which was statistically significant in the 3000 ppm group. Mild developmental toxicity was observed in the 3000 ppm group in the form of a reduction in mean fetal body weight. This reduction was statistically significant for the males only, although the relative decrease from the control values was the same for both sexes. There was no increase in the incidence of resorptions or the number of litters with resorptions among mice exposed to MEK. There was no significant increase in the incidence of any single malformation, but several malformations which were not observed in the concurrent control group or the controls of contemporary studies were present at a low incidence--cleft palate, fused ribs, missing vertebrae, and syndactyly. There was also a significant trend for increased incidence of misaligned sternebrae, a developmental variation. In summary, pregnant Swiss (CD 1) mice were relatively insensitive to the toxic effects of MEK at the inhaled concentrations used in this study. However, the offspring of the mice exhibited significant signs of developmental toxicity at the 3000 ppm exposure level.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1884914 TI - Subchronic oral toxicity of glyoxal via drinking water in rats. AB - The subchronic oral toxicity of glyoxal via drinking water and the effect on in vivo protein synthesis in tissues following a single treatment with this substance were assessed in Sprague-Dawley male rats. Animals received drinking water containing glyoxal levels of 2000, 4000, and 6000 mg/liter ad libitum for 30, 60, and 90 days in Phase I. In Phase II, the high-dose and control-1 groups fed the diet ad libitum, and a diet-limited control-2 group given the same amount of diet as consumed by the high-dose group were maintained for 90 and 180 days. The study designs included observations of clinical signs, body weights, major organ weights, gross and histopathological examinations, serum clinical chemistry, and biochemical examinations such as glyoxalase activity and glutathione content in selected tissues. Body weight gain and organ weights significantly decreased with dosage. Although consumption of food and water was also depressed in the exposed group, the reduction of body weight gain was greater in the high-dose group than in the diet-limited control 2 group. Histopathological examinations revealed only a slight papillary change in the kidneys from the high-dose group at both 90 and 180 days terminations in Phase II. The induction of both glyoxalase I and II was observed in liver and erythrocytes at 30-day termination of the exposed groups. Serum enzyme and protein levels were significantly reduced by the mid- and/or high-dose exposures. With a single oral high-dose treatment of glyoxal, a great decline in the incorporation of L-[3H]leucine was shown particularly in the liver, and this probably led in part to a reduction in the serum protein levels in rats following subchronic exposure to glyoxal. These data indicated an overall low degree of systemic toxicity to rats exposed subchronically to glyoxal via drinking water. PMID- 1884916 TI - Magnetic resonance microscopy of toxic renal injury induced by bromoethylamine in rats. AB - The alkylhalide 2-bromoethylamine hydrobromide (BEA) produces renal injury in rats that mimics analgesic-related renal injury in humans. Our purpose was to examine this injury, in vivo in rats, with magnetic resonance (MR) microscopy and correlate MR findings with findings from light microscopy of hematoxylin-eosin stained sections. Rats (n = 48) were injected intravenously with BEA (150 mg/kg) or saline and imaged with MR 6, 48, and 336 hr later. The spin-spin relaxation time, T2, was measured from the cortex to the papilla. In other rats, we measured regional water content of the kidney. Renal injury was present 48 and 336 hr after BEA dosing based on increased renal organ weights, decreased urine specific gravity, and significant renal lesions (H & E). T2 was elevated in the inner stripe of the outer medulla in injured kidneys at 48 hr. The differences in T2 between cortex and outer medulla were also elevated 48 hr after BEA. In the inner medulla, there were no changes in T2 after BEA treatment. However, in all groups there were significant regional differences in T2. The value of T2 increased from outer to inner medulla and this gradient was directly correlated with water content. Thus, MR microscopy detected damage in the outer medulla after BEA injury but not the damage in the inner medulla. T2 appeared to reflect the water content in the different regions of the medulla. The noninvasive in vivo capability of MR microscopy, with its high sensitivity to tissue water, allows the toxicologist to monitor the progression and regression of toxic insult in the same animal. At present the technology is complicated. The precise and accurate measure of MR-sensitive parameters in live animals at microscopic resolution is difficult. However, as the technology matures, there will be significant improvements providing the toxicologist a unique in vivo tool. PMID- 1884915 TI - Effect of chronic exposure of PCB (Aroclor 1254) on specific and nonspecific immune parameters in the rhesus (Macaca mulatta) monkey. AB - The immunomodulatory effects of low-level, chronic polychlorinated biphenyl PCB; (Aroclor 1254) exposure were investigated in female rhesus (Macaca mulatta) monkeys. Five groups of monkeys (initially 16 monkeys/group) were orally administered PCB at levels of 0, 5, 20, 40 or 80 micrograms/kg body wt/day. Tests for immunomodulation were initiated after 55 months of exposure to PCBs. Statistically significant observed immune changes included a dose-related decrease in the anamnestic (IgM and IgG) response to sheep red blood cells. Conversely, the antibody response to pneumococcus antigen did not differ significantly across the test groups. A statistically significant dose-related decrease in lymphoproliferation was noted with increasing doses of PCBs when phytohemagglutinin and Concanavalin A, but not when pokeweed mitogen, were used as mitogens. A trend toward reduced peak chemiluminescence (mV/min) was observed in zymosan-activated peripheral blood monocytes. The time to peak chemiluminescence of phorbol myristate acetate activation was statistically increased in a dose-response fashion. Flow cytometric analysis results of peripheral blood lymphocytes using the markers CD4, CD8, and CD20 were similar across the test groups. The mean percentage levels for the CD2 marker in the treated groups were statistically lower than the mean in the control, while absolute numbers for CD2 were similar across the test groups. Serum hydrocortisone levels did not differ among the test groups. Taken together these results indicate that low-level, chronic PCB exposure alters a number of rhesus monkey immune system components and that these effects may be due to altered T cell and/or macrophage function. These data may be of use in extrapolating potential human health effects following chronic PCB exposure. PMID- 1884917 TI - Pretreatment with drinking water solutions containing trichloroethylene or chloroform enhances the hepatotoxicity of carbon tetrachloride in Fischer 344 rats. AB - Previous studies have demonstrated that various compounds, including the common groundwater contaminants trichloroethylene (TCE) and chloroform (CHCl3), can produce a synergistic toxic response when coadministered with the model hepatotoxicant carbon tetrachloride (CCl4). This phenomenon has not, however, been demonstrated following administration of these compounds in drinking water. Initial experiments indicated that Fischer 344 (F-344) rats were significantly more sensitive to these effects than the more commonly utilized Sprague-Dawley strain. To establish the suitability of this strain as a model, a variety of indicators of hepatotoxicity was evaluated and compared to histological evidence of injury 24 hr after dosing with CCl4 or a combination of CCl4 + TCE. Plasma alanine aminotransferase (ALT) activity was the most reliable indicator of hepatic injury and was well-correlated with the histologic data. Dose-response studies utilizing simultaneous ip dosing confirm the sensitivity of the F-344 rat, demonstrating synergistic toxicity at doses as low as 0.165 mmol/kg of CCl4 and 0.6 mmol/kg of TCE. Synergism was also detected following simultaneous ip administration of 1 mmol/kg CCl4 and 0.5 mmol/kg of CHCl3. To evaluate the effects of drinking water exposure, rats were pretreated for 3 days with solutions containing TCE (0-40 mM) or CHCl3 (0-8 mM) stabilized with 1% Emulphor (EL-620P) as their only source of fluids. A single, ip dose of CCl4 (1 mmol/kg) was then administered and 24 hr later animals were killed for examination of liver histology and determination of ALT activity. Although none of the pretreatments were detectably hepatoxic, rats which drank 15 and 40 mM TCE or 8 mM CHCl3 exhibited an enhanced response to CCl4. PMID- 1884919 TI - Estimation of epidermal carcinogenic potency. PMID- 1884918 TI - Influence of chronic exposure to uranium on male reproduction in mice. AB - Relatively few data are available concerning the reproductive and developmental toxicity of uranium. The present study was designed to evaluate the reproductive effects of this metal in male Swiss mice. The animals were treated with uranyl acetate dihydrate at doses of 0, 10, 20, 40, and 80 mg/kg/day given in the drinking water for 64 days. To evaluate the fertility of the uranium-treated males, mice were mated with untreated females for 4 days. There was a significant but non-dose-related decrease in the pregnancy rate of these animals. Body weights were significantly depressed only in the 80 mg/kg/day group. Testicular function/spermatogenesis was not affected by uranium at any dose, as evidenced by normal testes and epididymis weights and normal spermatogenesis, whereas interstitial alterations and vacuolization of Leydig cells were seen at 80 mg/kg/day. The results of this investigation indicate that uranium does not cause any adverse effect on testicular function in mice at the concentrations usually ingested in the diet and drinking water, with a safety factor of more than 1000. However, although spermatogenesis was not affected by uranium administration, uranium produces a significant decrease in the pregnancy rate at 10, 20, 40, or 80 mg/kg/day. PMID- 1884920 TI - Rubella research and the Rosser family. PMID- 1884921 TI - Measuring affective derivatives of unfulfilled success expectancy. PMID- 1884922 TI - The abnormal curve: the pursuit of excellence in selecting and training residents. PMID- 1884923 TI - Composition of Delphi panel. PMID- 1884924 TI - Chlamydia trachomatis testing. PMID- 1884925 TI - Medicare reimbursement adjustments. PMID- 1884926 TI - Social support and health: where do we go from here? PMID- 1884927 TI - Why medical students change to and from primary care as career choice. AB - While many factors have been proposed to explain the specialty choice decisions of medical students, little has been reported on the reasons for change of career choice during medical school. The purpose of this study was to determine why medical students switched from primary care to nonprimary care as a career choice and why others changed from nonprimary care to primary care as a specialty preference. Of the 1981-1990 graduates of Wright State University School of Medicine (n = 832) investigated, 217 switched preference during medical school (53 to primary care, 164 to nonprimary care). Reasons relating to the medical school experience were more influential than personal or societal reasons, more so for students changing to nonprimary care than for those changing to primary care. Increased awareness of specialties and positive clinical experience in chosen specialties were indicated by 76% and 70% of those who switched. Among reasons selected less frequently, content and emphasis of the curriculum (19% versus 7%) and location of residency (17% versus 6%) were more likely to be cited by those switching to primary care than by those who switched to nonprimary care, while better financial opportunities were more important for those who switched to nonprimary care (17% versus 4%). PMID- 1884928 TI - The role of the rural hospital emergency department. AB - Although rural hospital emergency departments are key components of rural health care, there is little medical literature describing their activities. This study examined the patient load of rural emergency departments in Mississippi. Each patient encounter was coded according to public health district, hospital number, patient number, age, sex, race, season, day of week, time, diagnosis, disposition, and method of payment (if available). The rural emergency departments were much busier when physician offices were closed, with the vast majority of patients being treated and sent home. Users of rural emergency departments had similar diagnoses and dispositions to users of urban emergency departments. Admitted patients tended to be older; almost one half of the patients transferred to other institutions had injuries. The findings have implications for the training of rural physicians and for policies relating to rural health care delivery. PMID- 1884929 TI - The living will: a national survey. AB - This national survey examined the knowledge and use of the living will among 494 family physicians of the American Academy of Family Physicians in 39 jurisdictions with living will statutes. The findings revealed a positive relationship between physician knowledge of the living will and its clinical use. Additionally, a positive relationship between physician knowledge and willingness to initiate discussions on the document with patients was found. The implications of these findings, as related to disclosure of the living will in the informed consent process, is discussed. PMID- 1884930 TI - Validation of the Duke Social Support and Stress Scale. AB - The Duke Social Support and Stress Scale (DUSOCS) was validated in 249 adult family practice patients using the Family Strengths, the Family Inventory of Life Events, and the Duke Health Profile (DUKE) as comparison instruments. Validity was supported in that the DUSOCS family support measure had the clinically expected positive associations with DUKE health measures (regression coefficients of +7.4 to +18.7) and negative associations with DUKE anxiety and depression measures (-2.0 to -17.2). DUSOCS family stress had negative associations with the health measures (-11.6 to -34.5) and positive associations with anxiety and depression (+18.9 to +32.1). Family and non-family stress contributed more than severity of illness to elevated levels of anxiety and depression and lowered levels of mental health, social health, and self-esteem, while these same stresses contributed only half as much as severity of illness to lowered physical health. PMID- 1884931 TI - Smoking status and the practice of other unhealthy behaviors. AB - This study examined the relationship between smoking behavior and other unhealthy practices in the US. Data from the 1979 National Survey of Personal Health Practices and Consequences were used to compare alcohol use, sleep behavior, overweight status, physical activity, and skipping breakfast with smoking status. Compared with nonsmokers, smokers were more likely to sleep fewer than six hours per night, skip breakfast, not actively exercise, and drink heavily. Smokers were less likely to be significantly overweight than former smokers or those who never smoked. These associations were present for both men and women for sleep behavior, skipping breakfast, overweight status, and alcohol use, but not for physical activity. These findings may assist physicians in understanding the association between smoking and other practices that influence morbidity and mortality. PMID- 1884932 TI - Improving the yield of endocervical elements in a Pap smear with the use of the cytology brush. AB - A clinical trial assessed the efficacy of three different combinations of instruments for capturing endocervical elements when performing a Pap smear. The instrument combinations tested were: 1) the cytology brush and extended-tip wooden spatula; 2) moistened cotton swab and extended-tip wooden spatula; and 3) extended-tip wooden spatula and Ayre blunt spatula. Ninety-six eligible women seen for Pap smears were randomized to one of these three groups. In addition, two comparison groups were included to evaluate the effects of education about collection protocols and of strict protocol adherence. The cytology brush and extended-tip wooden spatula combination captured endocervical elements in 90.3% of Pap smears, compared to 66.7% for cotton swab and extended-tip wooden spatula, and 60.0% for Ayre spatula and extended-tip wooden spatula. The strict adherence to a collection protocol or education on tools and collection methods did not significantly increase the capture of endocervical elements. Widespread use of the cytology brush was introduced into the clinical setting after the study was completed and resulted in an increase to 80.1% capture rate for endocervical elements from a preexisting rate of 49.9%. PMID- 1884933 TI - The effects of social support on women's health during pregnancy, labor and delivery, and the postpartum period. AB - This review of the literature on social support and its relationship to maternal health indicates that emotional, tangible, and informational support are positively related to mothers' mental and physical health around the time of childbirth. The importance of various types of support changes with the changing needs of women as they move from pregnancy to labor and delivery, and then to the postpartum period. During pregnancy, emotional and tangible support provided by the spouse and others is related to the expectant mother's mental well-being. In addition, informational support in the form of prenatal classes is related to decreased maternal physical complications during labor and delivery, and to improved physical and mental health postpartum. Mothers who have the support of a companion during labor and delivery experience fewer childbirth complications and less postpartum depression. Mothers' postpartum mental health is related to both the emotional support and practical help (eg, housework and child care activities) provided by the husband and others. Health care providers are in a unique position to educate prospective parents about the importance of social support around the time of childbirth and may play a critical role in mobilizing support systems for new mothers. PMID- 1884934 TI - The family culture: a useful concept for family practice. AB - Each family can be regarded as a unique small-scale society, with its own internal organization and view of the world or family culture. A crucial aspect of each family culture are those beliefs, behaviors, habits, and life-styles that are either protective of health or pathogenic, depending on the context. For family physicians, the insights of medical anthropology are useful in understanding the role of family culture in health, illness, and medical care. PMID- 1884935 TI - Practical grantsmanship: the application process in health care research. AB - The creation of the Agency for Health Care Policy and Research presents expanded opportunities for research in primary care. This paper discusses the grant review process and includes section-by-section suggestions for successful proposal writing. Applicants should choose topics of their own interest, be aware of the funding agency's priorities, pick co-investigators who complement their own backgrounds and training, and perform at least some preliminary study of the topic which can be discussed in a proposal. Successful grantsmanship also requires patience, perseverance, and flexibility because several attempts may be necessary to receive funding. PMID- 1884936 TI - Improving a community preceptorship through a clinical faculty development program. AB - A department of family and community medicine has successfully used annual conferences to develop the teaching skills of clinical faculty. The conferences focus on specific topics each year, faculty are required to attend, and experienced preceptors are used as facilitators. These conferences have effectively improved the preceptors' abilities as teachers of medical students. This is dramatically illustrated by the increase in measurable objectives on the negotiated learning contracts. PMID- 1884937 TI - Cost rounds: presentations by residents on the cost of care. AB - Cost rounds are conferences on ambulatory medical care presented by third-year residents at the University of Washington in Seattle. The content includes data from a chart audit, charges for services in the clinic and laboratory, and suggested management guidelines. The chart audits stimulate interest in the conferences, and they are feasible when residents are provided with ways to identify patients by diagnosis, specific medication, or laboratory test. This program is a sustainable method of involving residents in discussions about the quality and cost of the care they deliver. PMID- 1884938 TI - Journal clubs and healthy skepticism. PMID- 1884939 TI - Current concepts in the pathophysiology and treatment of portal hypertension and variceal hemorrhage. AB - Recent studies have demonstrated that increased resistance to portal inflow is not solely responsible for the development of portal hypertension. Increased splanchnic flow has been attributed to a combination of factors, including elevated circulating levels of vasodilators and diminished sensitivity of the splanchnic vasculature to endogenous vasoconstrictors. In selected animal models of portal hypertension, increased splanchnic flow accounts for approximately 40% of the observed elevations in total portal venous pressure. Improved understanding of the pathophysiologic factors responsible for the development of portal hypertension has led to pharmacologic efforts to decrease portal pressure. Current limitations include lack of drug selectivity and specificity and inability to predict and monitor patient responses. Primary treatment options include selective portosystemic shunts, endoscopic sclerotherapy (ES), and orthotopic liver transplantation. ES is more effective in preventing recurrent variceal hemorrhage than medical treatment but is less effective than shunt surgery. In selected studies, ES better maintains hepatic function and may prolong survival compared to primary shunt surgery. ES failures occur in nearly 33% of patients, but "salvage shunts" in these patients appear to be reasonably safe and quite effective in preventing recurrent hemorrhage. Selective shunts are favored because they appear to confer a better quality of life (but not improved longevity) than conventional shunts. Liver transplantation is preferred for patients with end-stage liver disease in whom the predicted mortality of conventional surgery outweighs the survival benefit. PMID- 1884940 TI - The causes and management of lower GI bleeding: a study based on clinical observations at Hanyang University Hospital. AB - During the period of the study, lower GI bleeding patients comprised a constant 1.6% of the total admitted patients at Hanyang University Hospital annually. There were no statistically significant changes according to year. The 970 cases were classified as follows: hemorrhoid and anal fissure 65.5%, malignant neoplasm 21.1% (rectal cancer 16.9%, sigmoid colon cancer 3.3%, anal cancer 0.9%), benign neoplasm 4.2%, ulcerative colitis 3.3%, infectious colitis 2.3%, ischemic colitis 1.8%, radiation colitis 1.3%, diverticulosis 0.3%, and others 0.2%. Ulcerative colitis and rectosigmoid cancer showed increasing trends, while other disease groups showed no change in the occurrence rate. Hemorrhoid and anal fissure developed mostly in the 30s age group, benign polyp and ulcerative colitis in the 40s age group, malignant neoplasm in the 50s age group, and ischemic colitis and radiation colitis in the 60s age group. There was no sexual predominance of lower GI bleeding. About 10% of the patients admitted to the hospital needed transfusions, particularly patients with ulcerative colitis (21.9%) and radiation colitis (23.1%). 20.2% of the patients improved with supportive measures and medical treatment and 79.8% underwent surgical operation. In particular, 51.2% of the patients with benign neoplasm underwent polypectomies. PMID- 1884941 TI - Logical clinical decisions in the investigation and management of non-urgent rectal bleeding. AB - The benefits of assessment for non-urgent rectal bleeding derive from a combination of yield, risk factors, cost and patient comfort. Prospective studies have been completed which assign patients to investigative and management programmes based on graded bleeding patterns, the yield and true extent of flexible sigmoidoscopy and the safety and efficacy of immediate anorectal management. Between 1986 and 1989, 2268 new patients with bleeding were categorised by symptom grouping and entered into programmes of investigation and management. Flexible sigmoidoscopy (n = 936) eliminated or identified proximal bleeding in most (n = 882; 94.23%) and was confirmed to be generally specific for sigmoid assessment by "blinded" image intensifier confirmation of the level reached. No cancers are known to have been missed by clinical categorisation of patients. Between 1985 and 1988, 2112 patients underwent immediate sclerotherapy and triple banding for haemorrhoids, Significant secondary bleeding occurred in 9 patients (0.43%) and moderate to severe pain in 45 (2.13%) No deaths occurred. Further therapy to residual mucosal pedicles was required in 234 patients (11.08%) at one month, in 135 (6.39%) at a further month, and 67 patients (3.18%) subsequently. Careful clinical assessment, immediate investigation and management of the majority of anorectal disease in an ambulatory setting has been shown to be safe, highly cost efficient and relatively comfortable. PMID- 1884942 TI - Evaluation of HemoQuant test and enteroclysis in estimating the sites of obscure gastrointestinal bleeding. AB - The HemoQuant test includes the measurement of total fecal hemoglobin (Hb) or porphyrin derived from heme, and of intestinal converted fraction (ICF) which is the performed porphyrin probably by bacteria during enterocolic transit. The mean +/- SD of HemoQuant in 31 healthy subjects was 0.57 +/- 0.49 mg Hb/g stool, values above 2 mg Hb/g stool are considered to be positive. In patients with upper GI bleeding (n = 44), small bowel bleeding (n = 11) and large bowel bleeding (n = 16), the ICF ranged 0.03-23%, 0.09-20.20% and 0.35-11.0%, respectively. There was major overlap in individual ICF due to some influencing factors such as the quantity of fecal blood and the enterocolic transit. We conclude that HemoQuant is a sensitive assay for detection of fecal occult blood, but ICF is not helpful in estimating the anatomic site of bleeding. Seventy-one patients with GI bleeding of obscure origin underwent enteroclysis. The results showed 77.5% had definite lesions in the small bowel, but 22.5% still were undefined. It is suggested that enteroclysis should be performed without delay if upper and lower GI endoscopic studies are negative. PMID- 1884943 TI - Emergency colonoscopy for the diagnosis of lower intestinal bleeding. AB - During the past 8 years, we performed emergency colonoscopy in 206 patients in whom severe bloody stools suggested bleeding of the lower digestive tract. The site of hemorrhage could be determined in 184 patients (89.3%). In cases with severe hemorrhage, the causes were stercoral rectal ulcer and bleeding from the small intestine or the upper GI tract. The bleeding tended to be mild in patients with other colon diseases. Determination of the bleeding site was impossible or difficult when a large amount of blood was present in the intestinal lumen or the blood was completely discharged. These observations suggest that emergency colonoscopy is effective for determination of the site of GI bleeding, but improvements are considered to be needed especially in the preparation for the examination in patients in critical condition. PMID- 1884944 TI - Aggressive colonoscopic approaches to lower intestinal bleeding. AB - The most obvious advantage of colonoscopy is to establish the diagnosis at any level of the colon by direct observation of the mucosal surface and identification of any active bleeding and or responsible lesions. It also enables therapeutic intervention. In a period of 18 years from 1973 to 1990, 230 emergency colonoscopic examinations were performed in 205 cases for evaluation of acute and severe bleeding from the lower intestinal tract. There were 108 men and 97 women. They appeared quite serious and needed constant medical supervision including shock treatment and blood transfusion. The ages of the patients varied from 5 months to 90 years old. There were 24 children in this series. Colonoscopy was performed within 48 hours after onset of anal bleeding. All examinations were done without fluoroscopy. It was necessary to reach the cecum in 66% of cases to determine the responsible lesions. Bleeding was identified in all except 11 cases (94.7%). Bleeding and the responsible lesions were both visualized in 147 cases (71.7%). The source of bleeding was located proximal to the ileocecal valve in 37 cases (18%). Much blood was found in the bowel which interfered observation in 14 cases. No bleeding nor lesions could be identified in 8 cases (3.9%). Most common causes of bleeding in adults were cancer, inflammatory lesions, ischemic colitis and vascular ectasia, while the most common cause of bleeding in children was juvenile polyp.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1884945 TI - The value of RI scintigraphy and angiography in small intestinal bleeding--report of eight cases. AB - We retrospectively reviewed eight cases of small intestinal bleeding and assessed the value of RI scintigraphy and angiography in diagnosing the bleeding site. The patients' average age was 56.2 years. Chief complaints was melena of variable degree. In most cases neither upper endoscopy nor colonoscopy was diagnostic. RI scintigraphy (Tc-99 labeled HSA) showed 75% of positive rate whereas angiography showed 66.7% (4/6) of positive rate. All four cases of leiomyosarcoma and leiomyoma demonstrated hypervascular stain and/or extra-vasation in angiography whereas RI scintigraphy failed to detect active GI bleeding in 2 of the 4 cases. Therefore angiography was considered useful for the detection of bleeding from leiomyoma and leiomyosarcoma which are often hypervascular. Scintigraphy is thought of most value in the demonstration of small amount of bleeding with minimum vascular abnormality. PMID- 1884946 TI - Long-term study of endoscopic sclerotherapy in Jakarta, Indonesia. PMID- 1884947 TI - Endoscopic sclerotherapy in the treatment of esophageal varices--Bangladesh experience. PMID- 1884949 TI - Factors influencing peptic ulcer frequency in Asian and Australasian countries. AB - A self-administered questionnaire to the participants of Kyoto Satellite symposium on peptic ulcer which was held on October 28th 1990 was conducted to reveal the background of health and medical system and condition that are thought to affect the clinical frequency of peptic ulcer. Their countries were Japan, South Korea, China, Taiwan, Hong Kong, the Philippines, Thailand, India, Australia and New Zealand. The questionnaires are composed of a demographic population, number of doctors, activities of gastroenterology related societies, education system for medical doctors and so on. Brief results of this investigation are reported. PMID- 1884948 TI - Portal hypertension caused by biliary cirrhosis. AB - Twelve patients with portal hypertension caused by biliary cirrhosis were treated from January, 1983- June. 1990. There were 6 women and 6 men. Age ranged from 20 to 50 years with an average of 35.5 years. In all patients, a significant feature of this series was the long period of biliary obstruction caused by bile duct stones (N = 7), congenital atresia of biliary tract (N = 1), Caroli disease (N = 1), sclerosing cholangitis (N = 1), sclerosing carcinoma of biliary tract (N = 1), and benign postoperative stricture of biliary tract (N = 1). The incidence was 6.6% in portal hypertension; 2.2% in biliary tract disease and 18% in intrahepatic cholelithiasis. Esophagogastric varices were demonstrated in 6 cases. In 5 cases with or without esophageal varices, varices around the extrahepatic bile duct were detected before or during operation. Some complications including poor liver function, dilated collaterals around extrahepatic bile duct and biliary infection with underlying biliary stones existed simultaneously, therefore the management of these cases was very difficult. There was no single approach to patients with portal hypertension caused by biliary cirrhosis and it should be treated as an individual basis. PMID- 1884950 TI - Descriptive and analytical epidemiology of peptic ulcer disease in Japan. PMID- 1884951 TI - Peptic ulcer in New Zealand. PMID- 1884952 TI - Epidemiology of peptic ulcer disease in Thailand. AB - Peptic ulcers are common in all regions in Thailand. The true prevalence and incidence of peptic ulcer among the population can never be accurately assessed. National data compiled from official annual reports from provincial hospitals as well as hospital-based data are at best selective and carry several drawbacks in the process of data collection. some generalizations can be made nevertheless. Between 1981 and 1988, the hospitalization rate for peptic ulcer cases throughout the country remained fairly constant at around 111 to 112 per 100,000 population. At a large hospital in Bangkok, the proportions of gastric ulcers and duodenal ulcers cases between 1983 and 1988 were comparable, with more gastric ulcers among females than the males. Mortality among hospitalized peptic ulcer cases declined from 3.4 in 1977 to approximately 2 cases per 100,000 population in 1981 and fell further slightly thereafter. Much more statistical compilation is needed, while clearer diagnostic criteria should be followed in documenting reporting peptic ulcer cases in hospitals in order to arrive at more meaningful interpretations. PMID- 1884953 TI - An epidemiological study of gastric to duodenal ulcer ratio in Asian countries. PMID- 1884954 TI - Variceal bleeding after endoscopic injection sclerotherapy: an analysis of 108 subjects undergoing endoscopic injection sclerotherapy. AB - Among 108 cases of endoscopic injection sclerotherapy (EIS) performed from January 1984 through September 1989, post-EIS variceal bleeding occurred in 38 case (35%). Death was significantly more frequent among the post-EIS bleeders than non-bleeders (55% v. 27%). Background factors were analyzed for failure to prevent bleeding. The curve of the cumulative non-bleeding rate following emergency EIS (21 cases) was significantly lower (P less than 0.01) than that following elective EIS (22 cases), and there was more frequent rebleeding (13/21 v. 7/22) within a shorter mean period of time (4.9 months v. 14.1 months) in the former; association of hepatocellular carcinoma was also more frequent (13/21 v. 3/22). Continuation of drinking showed no difference between post-EIS bleeders (5/38) and non-bleeders (9/70). After complete variceal eradication the curve of the cumulative non-bleeding rate was significantly higher than after incomplete eradication (P less than 0.001). Following prophylactic EIS (65 cases) there was significantly less frequent bleeding (P less than 0.01) than following EIS performed after variceal rupture (43 cases). The risk of variceal bleeding after EIS can be minimized by complete eradication of varices at the initial EIS. Prophylactic EIS was suggested to contribute to reducing the frequency of post EIS bleeding. PMID- 1884956 TI - Diagnostic approaches and treatment of peptic ulcer at Chulalongkorn University Hospital, Bangkok. AB - Gastroscopy is the main investigative tool in the diagnosis of peptic ulcers in Thailand. In spite of its potential diagnostic value, endoscopic biopsy for histologic diagnosis is reserved only for suspected malignant gastric ulcers. Regarding treatment, duodenal ulcers can be treated satisfactorily with either low-dose antacid or one of the various H2-blockers, while gastric ulcers show a fairly good healing response to site-protective agents. Further trials using potent acid inhibitors, antibiotics against helicobacter pylori and plaunotol are being investigated. PMID- 1884955 TI - An open trial on short-term omeprazole therapy for gastric and duodenal ulcers. AB - Omeprazole, a proton pump inhibitor, is a potent and long-acting gastric acid reducing agent. To assess its short-term efficacy and safety, 27 gastric ulcers (GU) and 40 duodenal ulcers (DU) in 64 patients were treated with 20 mg. Omeprazole was given once daily. At 2 weeks, the healing rate for gastric ulcers was 66% (18/27) and for duodenal ulcers, 78% (31/40). At 4 weeks, the healing rate was 85% and 95% for GU and DU, respectively. Pain relief was achieved after 2 weeks in 62% with GU and 61% in DU. There were no significant side effects noted during the treatment course. Omeprazole is effective and safe in the treatment of gastric and duodenal ulcers. PMID- 1884957 TI - Results of endoscopic variceal sclerotherapy: influence of etiology of portal hypertension and hepatic functional status. AB - In India 50% of patients with gastrointestinal bleeding bleed from esophageal varices. Causes of portal hypertension includes hepatic cirrhosis, non-cirrhotic portal fibrosis and extrahepatic portal obstruction. Endoscopic sclerotherapy is the treatment of choice to control continued active bleeding. Immediate hemostasis was not influenced by the etiology of portal hypertension. However, rebleeding episodes were lower, in extrahepatic portal vein obstruction than non cirrhotic portal fibrosis and cirrhotic patients. Child's status significantly influenced recurrence of bleeding and mortality which was lower in child's A than B and lower in B than C irrespective of etiology. Results of long term sclerotherapy were also influenced by the etiology of portal hypertension and hepatic functional status. Sclerotherapy was most effective in patients of (EHO), than (NCPF) followed by cirrhosis of the liver. PMID- 1884958 TI - Clinical treatment of gastroduodenal bleeding. AB - Our present study was conducted by cooperation between Departments of Internal Medicine and surgery of a hospital, which was highly significant because the results were comprehensive without a bias toward either department. The present report describes whether or not emergency operations have decreased because of progress in various conservative hemostatic methods for hemorrhagic ulcer and short-term and long-term prognoses after conservative therapy. Compared with the first 8-year period, the number of patients treated by conservative therapy increased with a definite decrease in that of emergency operations in the latter 8-year period. As for the results of conservative treatment, the rate of short term prognostic hemostasis was 81.3%. Of the long-term prognostic cases, ulcers recurred in 50%, accompanied by recurrent bleeding in 34.8%. These patients were again treated by conservative therapy, and hemostasis was successful in 95.7%. The mortality rate following conservative therapy was 13.7% in the first period and 11.0% in the latter period. The surgical mortality rate was 6.0% in the first period and 5.4% in the latter period. There was no surgical death among the patients undergoing palliative operation. Our therapeutic policy for hemorrhagic ulcer will be described based on these findings. PMID- 1884959 TI - Clinical evaluation of endoscopic hemostasis for bleeding gastric and duodenal ulcers. AB - The present study shows the excellent efficacy of endoscopic hemostatic therapy by ethanol injection. At the same time, the results emphasize the significant efficacy of intensive pharmaceutical treatment for peptic ulcer patients with clinical symptoms of hematemesis and/or melena. Concerning endoscopic hemostatic therapy, we prefer ethanol injection therapy to most other methods, such as laser irradiation, microtase or heat probe, because the ethanol injection method is the most simple, inexpensive, safe, technically easy, can be performed any time and in any place, and is more effective than other methods. In rare cases where direct ethanol injection into the exposed blood vessels is difficult, we do not hesitate to select other contact methods such as heat probe or microtase. PMID- 1884960 TI - Management of upper gastrointestinal bleeding--the Prince of Wales Hospital experience. PMID- 1884961 TI - A review of 1338 patients with acute upper gastrointestinal bleeding at Chulalongkorn University Hospital, Bangkok. AB - Acute upper gastrointestinal bleeding (UGIB) is a major gastroenterological problem in Thailand. Peptic ulcer has remained the leading cause of UGIB, followed by acute mucosal erosions, and variceal bleeding. In the present study, covering the period between 1980 and 1984, early endoscopic diagnosis was obtained in 82% of cases, while conservative treatment was effective in 83.6%. Factors associated with increased mortality were advanced age, shock, sepsis nonsteroidal anti-inflammatory drug (NSAID) ingestion, severe blood loss, associated diseases and surgical treatment. The overall mortality was 6.7 percent. PMID- 1884962 TI - Treating bleeding peptic ulcer with sustained achlorhydria. AB - A controlled randomized study and a subsequent prospective therapeutic trial have demonstrated the efficacy of an intensive therapy comprising hourly intravenous injections of 100 mg of cimetidine along with a continuous nasogastric infusion of a liquid antacid at the rate of 0.5 ml per minute in achieving achlorhydria and controlling bleeding in patients with bleeding peptic ulcer. We recommend that this regimen should be routinely employed for treating patients with bleeding peptic ulcer, at least in center that do not practise topical therapeutic modalities for control of bleeding. PMID- 1884963 TI - Endoscopic cautery using the heater probe as an alternative to operation for massive gastroduodenal haemorrhage. AB - Endoscopic cautery using the heater probe has been used by the author since 1981 for treatment of acute gastroduodenal haemorrhage. The technique has been used as an alternative to immediate operation in 175 patients who had clearly demonstrated a need for intervention. All 175 had suffered recurrent haemorrhage in hospital to a blood transfusion requirement of at least 3 litres. Ulcer patients were selected by being over 60 yrs old or otherwise unfit for operation. Early experience showed that the technique was not reliable for patients bleeding from large posterior duodenal ulcers, so 35 old or sick patients with duodenal ulcer were excluded from the series. There were no exclusions with patients bleeding from lesions proximal to the pylorus, and 82% of these were successfully treated. Even with avoidance of large posterior ulcers, only 47% of duodenal ulcer patients were able to safely avoid an operation. It is concluded that heater probe cautery can replace emergency operation in most patients bleeding from gastric lesions, but it has a limited role for patients bleeding from duodenal ulcer. PMID- 1884964 TI - Endoscopic bipolar electrocoagulation in upper gastrointestinal bleeding. AB - A total of 213 cases of upper gastrointestinal bleeding treated by bipolar electrocoagulation (BPEC) were reviewed and its efficacy in the management of massive bleeding was evaluated. Initial hemostasis was achieved by BPEC in 97.6% cases with an overall rebleeding rate of 17.1%. The majority of rebleeding occurred in patients with acute mucosal lesions who had serious underlying medical problems. There were no complications related to the procedure. Endoscopic BPEC safely arrested oozing to spurting bleeding and contributed greatly to the control of upper gastrointestinal bleeding. PMID- 1884965 TI - Experimental and clinical studies on heater probe hemostasis for upper gastrointestinal bleeding with special reference to comparison with ethanol injection. AB - The hemostatic effects in patients with upper gastrointestinal bleeding was evaluated using an endoscopic heater probe method and ethanol injection method. The heater probe method was effective in 94.4% of patients with few complications. The ethanol injection method was effective in 86.5% of patients. The heater probe method is considered to be an effective and safe technique in the treatment of upper gastrointestinal bleeding. PMID- 1884966 TI - Management of upper GI haemorrhage 1976-1987: a New Zealand regional study. AB - Since 1960 all cases of upper GI bleeding have been admitted to the GE team at Palmerston North Hospital, a lower North island centre (population 150,000). A management protocol has been established since 1976, with endoscopy within 24 hours, standardised investigations and agreed criteria for transfusion and surgical intervention. since 1978 all cases have been treated with H2 antagonists on admission. An annual audit has been performed to monitor performance. This study outlines the results of 865 patients (M512:F353) treated between 1976 and 1989. 61 cases required urgent surgery (7%), 36 patients died (4.1%)-the lowest reported mortality for any large series. The majority of deaths occurred from non gastroenterological causes. If the mortality rate from upper GI haemorrhage is to be controlled all cases must be closely supervised by an interested specialised team with agreed protocols and cooperation between medical and surgical specialties. It is important to review performance with a regular audit and protocols need to be revised as technology and knowledge develops. PMID- 1884967 TI - Effect of ethanol on endothelin-1 release from gastric vasculature. AB - The effects of ethanol on gastric vasculature in isolated vascularly perfused rabbit stomach was investigated. The isolated stomach was perfused with Krebs Henseleit solution containing 3% dextran bubbled with 95% O2 and 5% CO2 at a rate of 12 ml/min. After mixture and perfusion of 10 mM to 400 mM of ethanol, perfusion pressure and endothelin-1 concentration in effluent from gastric vasculature were measured. Perfusion pressure and endothelin-1 concentration in effluent increased in a dose-dependent manner with increasing ethanol concentrations. In conclusion, the data suggest that ethanol may stimulate the release of endothelin from gastric vasculature and may cause gastric ischemia due to vasoconstriction resulting in acute gastric mucosal injury. PMID- 1884969 TI - Effect of continuous intravenous infusion of secretin preparation (secrepan) in patients with hemorrhage from chronic peptic ulcer and acute gastric mucosal lesion (AGML). AB - The purpose of the present study was to investigate the hemostatic effect of continuous intravenous infusion of secrepan (secretin preparation, Eisai Company Ltd. Tokyo) on gastroduodenal hemorrhage in patients with chronic peptic ulcer and AGML (acute gastric mucosal lesion). The patients consisted of 37 cases of bleeding ulcer (13 cases of chronic peptic ulcer and 24 cases of AGML). Secrepan was infused at a rate of 2 U/kg/hr for the first 3 days and 0.5 U/kg/hr for the next 4 days. The cumulative hemostatic rate in the chronic peptic ulcer group was 53.9% after 36 hours, and 76.9% after 48 hours of infusion, but no significant change in rate was observed thereafter. The cumulative hemostatic rate in the AGML group was 52.2% after 36 hours, and 95.7% after 72 hours of infusion. The hemostatic rate in chronic peptic ulcer and AGML cases with only slight or moderate bleeding was 100%, and no recurrent hemorrhaging was observed. The hemostatic rate in chronic peptic ulcer cases with severe bleeding was 62.5% and in AGML cases with severe bleeding was 93.3%, and 7 of 15 cases showed recurrent hemorrhage. Our findings indicated that continuous intravenous infusion of secrepan had more favorable effects on AGML cases, than on chronic peptic ulcer cases. PMID- 1884968 TI - Endoscopic hemostasis of bleeding peptic ulcers: 1:10000 adrenalin injection vs. 1:10000 adrenalin +1% aethoxysclerol injection vs. heater probe. AB - To evaluate the efficacy of three endoscopic methods which utilize different mechanisms of hemostasis to control bleeding peptic ulcers, we performed a prospective randomized study in 83 patients. Thirty-two patients were treated with 1:10000 adrenalin (Group I), 29 patients with 1:10000 adrenalin +1% aethoxysclerol (Group II), and 22 patients with the heater probe (Group III). Gastric ulcers were the source of bleeding in 14, 15 and 12 patients while duodenal ulcers were the source in 16, 13 and 10 patients in Groups I, II and III, respectively. Two stomal ulcers were noted in Group I and 1 in Group II. Two spurters were treated in Group I and 4 in Group II, while 22, 13 and 10 oozers were treated in Groups I, II and III, respectively. Definitive hemostasis was achieved in 94%, 100% and 95% in Groups I, II and III, respectively while the rebleeding rate was 6.25%, 6.9% and 9% respectively. 1:10000 adrenalin injection alone or when combined with subsequent instillation of a sclerosing agent and heater probe application have comparable efficacy in the endoscopic control of bleeding peptic ulcers. PMID- 1884970 TI - Results of nonshunting operation and injection sclerotherapy for esophageal varices. AB - The results of a total of 523 nonshunting operations performed at our institution from 1964 to 1990 were analyzed and compared to those of chronic sclerotherapy. Although the overall operative mortality rate of nonshunting operations was low (26/523:5.0%), it was relatively high in Child's C cirrhotic patients (22/129:17%) and in those who underwent surgery on an emergency basis (14/60:23%). Cumulative survival rates of Child's C cirrhotic patients at 5 and 10 years (37.4%, 13.0%) following nonshunting operations were much lower than those of Child's A (76.6%, 54.9%) or Child's B (71.6%, 35.5%). One- and three year survival rates for patients treated with sclerotherapy were 90%, 72% in Child's A (22 patients), 82%, 49% in Child's B (47), and 56%, 30% in Child's C (50), while cumulative rebleeding rates at one and three years following sclerotherapy were 12%, 12% in Child's A, 18%, 27% in Child's B, and 35%, 55% in Child's C respectively. Our data indicated that nonshunting operations can be safely performed with a good long-term outcome in Child's A or B cases on an elective basis, and sclerotherapy may be the treatment of choice for emergency cases or for Child's C cases although the risk of rebleeding is high following sclerotherapy. PMID- 1884971 TI - Effects of vasopressin on gastric mucosal blood flow in portal hypertension. AB - In patients with portal hypertension, bleeding from the gastric mucosa is common, and is often treated with vasopressin (VP). VP reduces the portal pressure by contracting the arterioles of the abdominal organs. In normal rats, VP reduces the gastric mucosal blood flow (GMBF). However, it is not sure whether the reduction of the portal pressure by VP actually reduces the GMBF in patients with portal hypertension. Here, we studied the effects of VP on the GMBF of 24 patients with portal hypertension resulting from cirrhosis. The ICG15 test was done for 20 of the patients. We measured the GMBF of the antrum and body of the stomach using a laser Doppler flowmeter (Peliflux PF 2) connected with a gastrofiberscope without VP on one day and about 10 min after the start of administration of VP (0.4 U/min, i.v.) on another day. Unexpectedly, the GMBF was increased with VP in 14 of 22 patients at the antrum and in 19 of 24 patients at the body of the stomach. In the body of the stomach, there was correlation between the increase in the GMBF caused by VP and the results of the ICG15 test. A high ICG15 reflects high portal pressure, so this finding indicates that in high portal pressure, the GMBF is increased by VP, and in low portal pressure, the GMBF is decreased by VP. PMID- 1884972 TI - Lower gastrointestinal bleeding in inflammatory bowel disease. AB - An increasing number of patients with inflammatory bowel disease (IBD) have been observed over the past two to three decades at the Cleveland Clinic. This has allowed extensive follow-up and determination of long-term prognosis. The diseases are chronic, require medication over a long period of time, are frequently associated with the need for operation, and often have complications and recurrences. In addition, a substantial number of patients have onset disease at a young age and thus, the propensity for recurrences and complications makes IBD of significant clinical importance. The symptoms of IBD are chronic and usually include diarrhea and often malnutrition. Rectal bleeding is found in almost all patients with ulcerative colitis and in about 25% of patients with Crohn's disease. However, severe hemorrhage in IBD occurs in a small number (1 5%) of patients. When this occurs, it often does so as an episode which may be associated with severe illness systemically as well as creating diagnostic confusion. For patients with ulcerative colitis, the progressive severity of bleeding may be an important indication for surgery (colectomy); in Crohn's disease, patients with ileocolic location of disease are more likely to have severe hemorrhage, and may require resection as a result. Despite the similarities of Crohn's disease and ulcerative colitis, there are significant differences particularly in the long-term (greater than 10 years) follow-up. For patients with Crohn's disease, the major long-term problem is the need for surgery (2/3-3/4 of patients) and recurrence (+/- 50%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1884973 TI - Characterization and application of a murine monoclonal antibody that reacts specifically with the serogroup D1 Salmonella. AB - A murine hybridoma cell line that produces monoclonal antibody (mAb) against the serogroup D1 Salmonella lipopolysaccharide (LPS) antigen was established. The trisaccharide tyvelose alpha 1----3 mannose alpha 1----4 rhamnose was shown to be involved in the reactive epitope of the mAb since this mAb reacted strongly with strains of serogroup D1 Salmonella but not with Salmonella strains from the O serogroups of A, B, and D2, and sodium meta-periodate was found to destroy the reactivity of the serogroup D1 O-antigen with the mAb. As such this mAb was found to be a useful serotyping reagent for the identification of serogroup D1 Salmonella, and for the differentiation of strains of serogroups D1 and D2 Salmonella which have identical flagellar H antigens. PMID- 1884974 TI - Purification of the protein X of Streptococcus agalactiae with a monoclonal antibody. AB - The protein X of Steptococcus agalactiae is a surface antigen included in the typing scheme of group B streptococci (GBS). We have developed a monoclonal antibody to the protein X and used it to purify this antigen by affinity chromatography. Electrophoresis in polyacrylamide, and immunoblotting using the monoclonal antibody or a rabbit antiserum raised with the affinity purified protein X, revealed a major band in the region of 200 kDa and a smaller one at 100 kDa. The isolated protein X will make possible investigations of its potential role in virulence and protection. PMID- 1884975 TI - A staphylococcal plasmid that replicates and expresses ampicillin, gentamicin and amikacin resistance in Escherichia coli. AB - Plasmid pPG1 from Staphylococcus aureus coding for ampicillin (Apr), gentamicin (Gmr) and amikacin (Akr) resistance was transformed into Escherichia coli. Transformation efficiency was about 2 x 10(3) transformants/micrograms of plasmid DNA. The plasmids present in the E. coli transformants were identical to pPG1 according to their restriction patterns. The copy number of pPG1 was estimated to be at least 20-times less in E. coli than in S. aureus. The minimal inhibitory concentrations (MICs) for Ap and Gm were lower in E. coli than in S. aureus. However, the MIC for Ak was higher in E. coli transformants than in S. aureus. pPG1 was maintained in the E. coli transformants for at least 80 generations at 37 degrees C without antibiotic selection pressure. PMID- 1884976 TI - Suppression of penicillin-induced lysis of Staphylococcus aureus by cibacron blue 3G-A. AB - The effect of cibacron blue 3G-A (CB) on bacteriolysis induced by penicillin G was investigated using Staphylococcus aureus FDA 209P. Penicillin-induced lysis was completely inhibited by 30 microM CB. However, the bactericidal effect of penicillin G was not influenced by CB. These results indicate that a bacteriolytic process is not essential for penicillin to kill S. aureus. PMID- 1884977 TI - Phage resistance and altered growth habit in a strain of Streptococcus bovis. AB - Bacteriophage (phi Sb01) of Streptococcus bovis, isolated from pooled rumen fluid of cattle, was a small siphovirus of morphotype B1. It contained double-stranded DNA of length 30.9 kb, which was digested by the restriction endonucleases, EcoRI, HindIII, and PvuII. Bacteria which survived phi Sb01 infection (strain 2BAr) grew in long chains (100-200 cells), ultimately forming large clumps of cells. This growth habit was in distinct contrast to that of the parent host strain which grew predominantly in the form of single cells or diplococci. Strain 2BAr was genetically stable, resistant to phi Sb01 attack, and the observed differences in the growth characteristics of the parent strain and 2BAr indicated that cells of 2BAr were more adherent. In the rumen ecosystem, the selection of phage-resistant bacteria with altered growth characteristics may be a factor in modifying bacterial phenotypes, and thus increasing variability among bacteria which are closely related genetically. PMID- 1884978 TI - A dihydrofolate reductase gene from Candida albicans: molecular cloning. AB - The dihydrofolate reductase gene from Candida albicans has been cloned and partially characterized. A genomic bank from C. albicans strain 10127/5 was constructed in Escherichia coli and screened for trimethoprim resistance. A plasmid pMF1, carrying the resistance marker was isolated and characterized by restriction mapping and Southern blotting. Cells harbouring pMF1 were as sensitive as the parental cells to a wide spectrum of antibacterial agents, except for trimethoprim; the dihydrofolate reductase activity from these cells was trimethoprim resistant. PMID- 1884979 TI - The anaerobic utilisation of cyanide in the presence of sugars by microbial cultures can involve an abiotic process. AB - The degradation of cyanide under anaerobic conditions in the presence of a growing culture of a strain of Klebsiella planticola has been shown to be due to a chemical process dependent upon the presence of a reducing sugar in the medium. The conversion of cyanide to ammonia was independent of any biological factors under these conditions. PMID- 1884980 TI - Clonal relationships among Escherichia coli serogroup 06 isolates from human and animal infections. AB - The clonal relationship of thirty E. coli strains of 0 antigen serotype 06 isolated from human, dog, pig or cow infections were investigated. Two main clones with serotypes 06 : H1 or 06 : H31, H- were identified. Isolates from humans, dogs, pigs and cows were found in both clones, indicating that animals are a possible source for human extraintestinal Escherichia coli strains. Two human ETEC (06 : H16) and two pig isolates (06 : H10) were not related to the 06 : H1 or 06 : H31, H- E. coli clones. PMID- 1884981 TI - The 16S rRNA nucleotide sequence of Mycobacterium leprae: phylogenetic position and development of DNA probes. AB - The almost complete 16S rRNA sequence from Mycobacterium leprae was determined by direct sequencing of the chromosomal gene amplified by the polymerase chain reaction. The primary sequence revealed an insertion of 12 nucleotides at the 5' end of the 16S rRNA gene, which consists of an A-T stretch and appears to be unique for M. leprae. Within the mycobacteria M. leprae branches off with a group of slow-growing species comprising M. scrofulaceum, M. kansasii, M. szulgai, M. malmoense, M. intracellulare and M. avium. A systematic comparison of the nucleotide sequence resulted in the characterization of oligonucleotide probes which are highly specific for M. leprae. The probes hybridized exclusively to 16S rRNA nucleic acids from M. leprae, but not to nucleic acids from 20 cultivable fast- and slow-growing mycobacteria. PMID- 1884982 TI - Identification, cloning and sequencing of the replication region of Lactococcus lactis ssp. lactis biovar. diacetylactis Bu2 citrate plasmid pSL2. AB - The replication region of the 7.8 kilobase (kb) citrate plasmid pSL2 from Lactococcus lactis ssp. lactis biovar. diacetylactis Bu2 was identified. Deletion derivatives of pSL2 were introduced into plasmid-free strain Bu2-60 and tested for their ability to replicate autonomously. The region necessary for replication was identified by comparison of the pSL2 derivatives, cloned and sequenced. No homologies were detected by comparing the putative Rep protein of pSL2 with replicons of other plasmids of Gram-positive bacteria. A part of an IS-element flanking the replication region was found. PMID- 1884984 TI - Cloning and expression of various staphylococcal genes encoding urease in Staphylococcus carnosus. AB - The urease genes from Staphylococcus xylosus C2a, Staphylococcus aureus U500, and S. aureus Newman were cloned in Staphylococcus carnosus using the plasmid vectors pCA43 and pCA44. The resulting respective recombinant plasmids pUra 402, pUraUH66, and pUra17 contained chromosomal DNA fragments with sizes of 5.6, 5.8, and 6.8 kb, respectively. Investigations on urease expression of the donor and recombinant strains in media with various nitrogen sources revealed that S. xylosus C2a produced urease constitutively at the highest specific activity. All of the recombinant strains had significantly lower urease activities than their DNA-donor strains. The nickel-dependence of urease was demonstrated in S. aureus U500 by a plate diffusion assay. PMID- 1884983 TI - Analysis of the gene of Vibrio hollisae encoding the hemolysin similar to the thermostable direct hemolysin of Vibrio parahaemolyticus. AB - The gene (designated as Vh-tdh) of Vibrio hollisae 9041 encoding a hemolysin similar to the thermostable direct hemolysin (TDH) of V. parahaemolyticus contained a 567-base-pair open reading frame (ORF), which was 93.3-93.5% homologous to those of the tdh genes of V. parahaemolyticus, V. cholerae non-01, and V. mimicus encoding TDH or similar hemolysins. Comparative analysis of the nucleotide sequence containing the Vh-tdh ORF with published nucleotide and amino acid sequences suggested that the Vh-tdh gene and other tdh genes diverged from a common ancestral gene, that the divergence was closely associated with the evolutionary divergence of V. hollisae from other species of genus Vibrio, and that strain-to-strain variation of the Vh-tdh gene exists in V. hollisae. PMID- 1884985 TI - Isolation, purification and characterisation of 2-oxoglutarate reductase from Fusobacterium nucleatum. AB - 2-Oxoglutarate reductase from Fusobacterium nucleatum was isolated by thiol disulphide interchange covalent chromatography. The enzyme was purified approximately 4000-fold and had a molecular mass of 68 kDa. The Michaelis constants for 2-oxoglutarate and NADH were 6.4 x 10(-5) and 0.4 x 10(-5), respectively. The involvement of sulphahydryl groups in catalysis was shown from the inhibition of 2-oxoglutarate reduction in the presence of 2,2'-dipyridyl disulphide and reactivation with 2-mercaptoethanol. Allosteric effectors did not alter the rate of the reaction, or the enzyme stability. With the exception of 2 oxoglutarate, none of the other oxo-acids such as oxaloacetate, pyruvate, 2 oxobutyrate and glyoxylate were reduced. Although 2-oxoglutarate oxidised NADPH to a limited extent (3%), the enzyme was almost entirely specific towards NADH. 2 Oxoglutarate reductase was stable at 45 degrees C for 10 min, while incubation at 60 degrees C abolished all activity. PMID- 1884986 TI - Teichoic acid choline esterase, a novel hydrolytic activity in Streptococcus oralis. AB - Streptococcus oralis contains an enzyme that can remove a limited amount of choline residues when tested on purified cell walls. This activity has been identified as an esterase that exhibits some biochemical properties similar to those previously found for several lytic enzymes of S. pneumoniae and its bacteriophages. PMID- 1884987 TI - Identification of a telomeric fragment from the right arm of chromosome III of Aspergillus nidulans. AB - A minimum of 11 bands hybridising to an oligonucleotide complementary to the putative telomeric repeat sequence (TTAGGG)n was visible in a Southern blot of EcoRI-digested Aspergillus nidulans genomic DNA. All 11 were sensitive to BAL 31 exonuclease digestion, consistent with telomeric locations. Blots of DNA from aneuploid strains deleted for a dispensable, extreme distal region on the right arm of chromosome III lack a 1.3-kb EcoRI band, indicating that this fragment is located at or near the chromosome III right arm telomere. PMID- 1884988 TI - Physical characterisation of plasmids in a morpholine-degrading mycobacterium. AB - The plasmid content of an environmental mycobacterium (MorG) which degrades morpholine (Mor+ phenotype) was investigated. The combination, in what appears to be a novel way, of restriction endonuclease digestion, gel electrophoresis and scanning densitometry permitted the resolution of mixed plasmid preparations into four distinct plasmids with sizes of 54 (approximately), 27.7, 22.8 and 22.6 kb. These plasmids were named pMOR1, 2, 3 and 4, respectively. The Mor+ phenotype was found to be unstable during acriflavin treatment. In four independently isolated Mor- mutants, plasmid pMOR2 was found to have acquired an insert of approximately 1.8 kb within a specific 5.9 kb BamHI fragment. It is concluded that pMOR2 is involved in the coding of the Mor+ phenotype. PMID- 1884989 TI - Induction of barotolerance by heat shock treatment in yeast. AB - In Saccharomyces cerevisiae, heat shock treatment provides protection against subsequent hydrostatic pressure damage. Such an induced hydrostatic pressure resistance (barotolerance) closely resembles the thermotolerance similarly induced by heat shock treatment. The parallel induction of barotolerance and thermotolerance by heat shock suggests that hydrostatic pressure and high temperature effects in yeast may be tightly linked physiologically. PMID- 1884990 TI - The role of the serine protease active site in the mode of action of epidermolytic toxin of Staphylococcus aureus. AB - The sequences of the epidermolytic toxins and V8 serine proteinase share about 25% identity, including the catalytic triad at the proteinase active centre. Here we have altered the putative ETA active-site serine-195 to glycine by site directed mutagenesis. No epidermolytic activity was detected when up to 100-fold greater amounts of the homogeneous mutant ETA were injected subcutaneously into neonatal mice showing that serine-195 is required for toxicogenesis. PMID- 1884991 TI - In vitro cytotoxicity of Haemophilus influenzae lipopolysaccharides for bovine aortal endothelial cells. AB - The cytotoxicity of purified lipopolysaccharide (LPS) from a prototype Haemophilus influenzae type b (Hib) strain (Eagan) and three transformants, differing in their LPS phenotype, for bovine aortal endothelial cells (BAOEC) was investigated. All LPS preparations caused cell disruption and release of lactate dehydrogenase (LDH), an indicator of cytotoxicity, from BAOEC monolayers but to differing extents. There was no correlation between the cytotoxicity of purified Hib LPS to BAOEC monolayers and potential to cause bacteraemia in experimental animals. PMID- 1884992 TI - Cloning and expression of the Arthrobacter globiformis KZT1 fcbA gene encoding dehalogenase (4-chlorobenzoate-4-hydroxylase) in Escherichia coli. AB - The fsbA gene controlling the first step of 4-chlorobenzoic acid (4CBA) metabolism in the Gram-positive soil bacterium Arthrobacter globiformis KZT1 has been cloned and analysed in Escherichia coli. The E. coli minicells analysis showed that a polypeptide(s) with Mr = 58 kDa (and/or Mr = 32 kDa) can be the fcbA product(s). Despite the gene dose amplification and control of the E. coli inducible Plac promoter, the level of functional expression of the fcbA gene in E. coli cells seems comparable only with that in the parental KZT1 strain. Effective 4CBA dechlorination by recombinant cells during growth in the presence of substrate within a range of concentrations 0.1 g/l to 0.7 g/l as well as a sudden reduction in the reaction efficiency at higher substrate concentrations were observed. PMID- 1884993 TI - Genetic control of degradation of chlorinated benzoic acids in Arthrobacter globiformis, Corynebacterium sepedonicum and Pseudomonas cepacia strains. AB - The strains of Arthrobacter globiformis KZT1, Corynebacterium sepedonicum KZ4 and Pseudomonas cepacia KZ2 capable of early dehalogenation and complete oxidation of 4-chloro-, 2,4-dichloro-and 2-chlorobenzoic acids, respectively, have been analyzed for the origin of the genetic control of degradation. The occurrence and molecular sizes of plasmids in all the strains have been established. Plasmid pBS1501 was shown to control 4-chlorobenzoate dehalogenation in the case of KZT1 strain. The same possibility is proposed for plasmid pBS1502 for dehalogenation of 2,4DCBA by KZ4 strain. The chromosome localization of the genes controlling oxidation of 4-hydroxybenzoate in strain KZT1 is shown. Localization of the whole set of genes responsible for 2CBA degradation in the strain KZ2 chromosome is suggested. PMID- 1884994 TI - Multilocus genetic relationships between clinical and environmental Aeromonas strains. AB - Allelic variations in the chromosomal genome of 120 isolates of motile Aeromonas (A. hydrophila, A. sobria and A. caviae) and eight reference strains with one Plesiomonas shigelloides were assessed by analysis of electrophoretically demonstrable polymorphism in 16 genes encoding metabolic enzymes. The strains were collected from humans (n = 59) and from the aquatic environment (n = 61) in canton Tessin, Switzerland. Clustering of the electrophoretic types (ET) from a matrix of pairwise genetic distances, based on the 16 enzyme loci, confirmed the genetic distinctness of the three species. Furthermore, A. hydrophila and A. sobria were divided in three and two groups respectively. For each species clinical strains were well differentiated from those collected in the environment. PMID- 1884995 TI - Escherichia coli accumulates the eukaryotic osmolyte taurine at high osmolarity. AB - Escherichia coli accumulated taurine at high osmolarity via the ProU and ProP transport systems. Taurine accumulation was shown to be osmotically active as it displaced cytoplasmic K+. In contrast to betaine and proline, taurine only modestly enhanced the growth rate of E. coli at high osmolarity and only if the cell was unable to synthesise trehalose. These studies show that taurine cannot be used as a tracer for the extra-cytoplasmic space of bacteria grown at high osmolarity. PMID- 1884996 TI - The proteolytic system of the fission yeast Schizosaccharomyces pombe. AB - Proteinase and peptidase activities of the fission yeast Schizosaccharomyces pombe were investigated. Several intracellular proteolytic enzymes were found: two endoproteinases, one carboxypeptidase, one aminopeptidase and one dipeptidyl aminopeptidase. In addition, proteinase inhibitors were detected. In fresh crude extracts an activation procedure is needed to measure maximal activities of endoproteinases and carboxypeptidase, whose level is markedly dependent on growth medium composition and on growth phase, while aminopeptidase and dipeptidyl aminopeptidase activities are very little, if at all, regulated by the carbon source. PMID- 1884997 TI - Overproduction of a Clostridium cellulolyticum endoglucanase by mutant strains of Escherichia coli. AB - We have studied the expression of an endoglucanase from Clostridium cellulolyticum in mutant strains of Escherichia coli that overproduce haemolysin. When these mutants were transformed with plasmids encoding the endoglucanase, they showed a significantly enhanced endoglucanase activity, compared to transformed parental strains. Among the mutants, strain Hha-2 showed the highest production. We have identified the endoglucanase gene product synthesized in E. coli Hha-2/pBP8 and detected an increased amount of the enzyme parallel to the increase of endoglucanase activity. This was mainly localized in the periplasm and only a small percentage of it was found in the culture fluid. PMID- 1884998 TI - A family of C/EBP-related proteins capable of forming covalently linked leucine zipper dimers in vitro. AB - Mouse and rat genomic DNA libraries were screened by reduced stringency hybridization with the DNA-binding domain of the c/ebp gene as a probe. Three genes were isolated that encode bZIP DNA-binding proteins (designated CRP1, CRP2, and CRP3) with strong amino acid sequence similarities to the C/EBP-binding domain. CRP2 is identical to the protein described recently by other groups as NF IL6, LAP, IL-6DBP, and AGP/EBP, whereas CRP1 and CRP3 represent novel proteins. Several lines of evidence indicate that these three proteins, along with C/EBP, comprise a functional family. Each bacterially expressed polypeptide binds to DNA as a dimer with recognition properties that are virtually identical to those of C/EBP. Every member also bears a conserved cysteine residue at or near the carboxyl terminus, immediately following the leucine zipper, that at least in vitro allows efficient disulfide cross-linking between paired zipper helices. We developed a gel assay for covalent dimers to assess leucine zipper specificities among the family members. The results demonstrate that all pairwise combinations of dimer interactions are possible. To the extent that we have examined them, the same heterodimeric complexes can be detected intracellularly following cotransfection of the appropriate pair of genes into recipient cells. All members are also capable of activating in vivo transcription from promoters that contain a C/EBP-binding site. Our findings indicate that a set of potentially interacting C/EBP-like proteins exists, whose complexity is comparable to that of other bZIP protein subfamilies such as Jun, Fos, and ATF/CREB. PMID- 1884999 TI - twist and snail as positive and negative regulators during Drosophila mesoderm development. AB - twist and snail are members of the helix-loop-helix and zinc-finger protein families, respectively, and determine the development of the mesoderm in Drosophila. This paper analyzes their role in mesoderm development by examining how they affect the expression of downstream genes. twist and snail act by regulating gene expression in the mesoderm and in neighboring regions, and have distinct roles in this process. snail prevents expression in the mesoderm of genes that are destined to be active only in more lateral or dorsal regions. twist is required for the activation of downstream mesodermal genes. twist is also required for the full expression of snail and for the maintenance of its own expression. Only the absence of both twist and snail results in the complete loss of all mesodermal characteristics. PMID- 1885000 TI - Neuroectoderm in Drosophila embryos is dependent on the mesoderm for positioning but not for formation. AB - By studying neuroectoderm formation in the absence of mesoderm and mesectoderm in mutants of the zygotic genes snail and twist, we have found that the number of neuroblasts is not reduced in these mutants, suggesting that mesoderm and mesectoderm are not essential for the initiation of neural development. The position of the neuroectoderm, however, is ventrally shifted: Neuroectoderm takes over the presumptive peripheral mesoderm domain in single mutants, whereas the entire presumptive mesoderm domain in double mutants takes on the neuroectodermal fate. The shifted neuroectoderm still requires the proneural genes and the neurogenic genes. This shift is unlikely to be due to any shift in the nuclear localization gradient of the maternally supplied dorsal protein. A model for cell fate determination of the neuroectoderm, mesectoderm, and mesoderm will be discussed. PMID- 1885001 TI - Replication factor-A from Saccharomyces cerevisiae is encoded by three essential genes coordinately expressed at S phase. AB - Replication factor-A (RF-A) is a three-subunit protein complex originally purified from human cells as an essential component for SV40 DNA replication in vitro. We have previously identified a functionally homologous three-subunit protein complex from the yeast Saccharomyces cerevisiae. Here we report the cloning and characterization of the genes encoding RF-A from S. cerevisiae. Each of the three subunits is encoded by a single essential gene. Cells carrying null mutations in any of the three genes arrest as budded and multiply budded cells. All three genes are expressed in a cell-cycle-dependent manner; the mRNA for each subunit peaks at the G1/S-phase boundary. A comparison of protein sequences indicates that the human p34 subunit is 29% identical to the corresponding RFA2 gene product. However, expression of the human protein fails to rescue the rfa2::TRP1 disruption. PMID- 1885002 TI - Proteolytic removal of core histone amino termini and dephosphorylation of histone H1 correlate with the formation of condensed chromatin and transcriptional silencing during Tetrahymena macronuclear development. AB - During the sexual cycle in Tetrahymena, the germ-line micronucleus gives rise to new macro- and micronuclei, whereas the former somatic macronucleus ceases transcription, becomes highly condensed, and is eventually eliminated from the cell. With polyclonal antibodies specific for acetylated forms of histone H4, immunofluorescent analyses have demonstrated that transcriptionally active macronuclei stain positively at all stages of the life cycle except during conjugation, when parental macronuclei become inactive and are eliminated from the cell. In this report using affinity-purified antibodies to either the acetylated or unacetylated amino-terminal domain of H4, immunofluorescent analyses suggest that the acetylated amino-terminal tails of H4 are proteolytically removed in "old" macronuclei during this period. This suggestion was further confirmed by biochemical analysis of purified old macronuclei that revealed several polypeptides with molecular mass 1-2 kD less than that of intact core histones. These species, which are unique to old macronuclei, are not newly synthesized and fail to stain with either acetylated or unacetylated H4 antibodies. Microsequence analysis clearly shows that these polypeptides are proteolytically processed forms of core histones whose amino-terminal "tails" (varying from 13 to 21 residues) have been removed. During the same developmental period, histone H1 is dephosphorylated rapidly and completely in old macronuclei. These results strongly suggest that the developmentally regulated proteolysis of core histones and dephosphorylation of histone H1 participate in a novel pathway leading to the formation of highly condensed chromatin and transcriptional silencing during Tetrahymena macronuclear development. PMID- 1885003 TI - Characterization of a Drosophila protein associated with boundaries of transcriptionally active chromatin. AB - We have used indirect immunofluorescence of polytene chromosomes to examine the chromatin distribution of a 52-kD Drosophila protein designated B52. B52 is localized to transcriptionally active loci and, at the highly decondensed heat shock loci, can be seen to bracket the RNA polymerase II fluorescence signals symmetrically. We have also examined the distribution of B52 on nonpolytene chromosomes in Drosophila cell cultures with an in vivo UV cross-linking method and find that, here too, B52 is associated with boundaries of transcriptionally active chromatin. The predicted primary amino acid sequence of B52 reveals two regions with similarities to a number of other proteins known to interact with nucleic acids. PMID- 1885004 TI - Configuration of DNA strands and mechanism of strand exchange in the Hin invertasome as revealed by analysis of recombinant knots. AB - The Hin recombinase of Salmonella normally catalyzes a site-specific DNA inversion reaction that is very efficient when the Fis protein and a recombinational enhancer sequence are present. The mechanism of this recombination reaction has been investigated by analyzing the formation and structure of knots generated in different plasmid substrates in vitro. Hin seldom knots the wild-type substrate under standard recombination conditions. However, we show that increasing the length of DNA between the recombination sites and the enhancer and changing the sequence of the core nucleotides where strand exchange occurs increases the efficiency of the knotting reaction. The structure of the knots generated by different mutant substrates strongly supports a model involving a unique configuration of DNA strands at synapsis and DNA strand exchange mediated by rotation of one set of Hin subunits after DNA cleavage. Analysis of the stereostructure of the knots by electron microscopy of RecA coated DNA molecules demonstrates that the direction of subunit rotation is exclusively clockwise. Because multiple subunit rotations generating knotted molecules do not occur efficiently when the enhancer is located in its native position, we suggest that the enhancer normally remains associated with the two recombination sites in the invertasome structure during strand exchange to limit strand rotation once it has been initiated. Under certain conditions, however, complex knots are formed that are probably the result of the premature release of the enhancer and multiple, unrestrained subunit exchanges. PMID- 1885005 TI - Alignment of recombination sites in Hin-mediated site-specific DNA recombination. AB - The Hin site-specific recombination system normally promotes inversion of DNA between two recombination sites in inverted orientation. We show that the rate of deletion of DNA between two directly repeated recombination sites is 10-300 times slower than inversion between sites in their native configuration as measured in vivo and in vitro, respectively. In vitro studies have shown that the deletion reaction has the same requirement for Fis, a recombinational enhancer, and DNA supercoiling as the inversion reaction. These requirements, together with the finding that the deletion products are interlinked once suggest that the deletion synaptic complex is similar to the invertasome intermediate that generates inversion. The inefficiency of the deletion reaction is not a function of a reduced ability to recognize or synapse recombination sites in direct orientation. Not only do these substrates support an efficient knotting reaction, but directly repeated recombination sites with symmetric core sequences also invert efficiently. These findings demonstrate that the recombination sites are preferentially assembled into the invertasome structure with the sites aligned in the configuration for inversion regardless of their starting orientation. We propose that the dynamics of a supercoiled DNA molecule biases the geometric assembly of specific intermediates. In the case of Hin-mediated recombination, inversion is overwhelmingly preferred over deletion because DNA supercoiling favors a specific alignment of DNA strands in the synaptic complex. PMID- 1885006 TI - Different activation domains of Sp1 govern formation of multimers and mediate transcriptional synergism. AB - The process of transcriptional activation in eukaryotes by site-specific DNA binding proteins is a key step in gene regulation. Here we have examined the properties of four distinct activator domains of the human transcription factor Sp1. In vivo transient cotransfection assays with Sp1 show that templates bearing multiple Sp1 sites activate transcription with a high degree of synergism. However, there is no evidence of cooperative binding of Sp1 to adjacent sites. Using deletion mutants of Sp1 we have determined that the glutamine-rich activation domains A and B and the previously uncharacterized carboxy-terminal domain D are all required for Sp1 to activate transcription synergistically. Gel shift, DNase footprinting, and chemical cross-linking experiments reveal a strong correlation between the ability of Sp1 mutants to form homomultimeric complexes and their ability to activate transcription synergistically when bound to multiple sites. We have also examined the process of superactivation, in which a molecule of Sp1 tethered to DNA via its zinc fingers can be transcriptionally enhanced by interacting directly with fingerless Sp1 molecules. The domains involved in superactivation appear to be a subset of those necessary to achieve synergistic activation. These findings suggest that different domains of Sp1 carry out distinct functions and that the formation of multimeric complexes may direct synergism and superactivation. PMID- 1885007 TI - Multiple processing-defective mutations in a mammalian histone pre-mRNA are suppressed by compensatory changes in U7 RNA both in vivo and in vitro. AB - To study the role of base-pairing between the mammalian U7 snRNA and the highly variable histone downstream element (HDE) during the 3'-end maturation of mammalian histone pre-mRNAs, we mutated the HDE of the mouse H2A-614 gene and assayed processing in HeLa cells both in vivo and in vitro. Either a 9-nucleotide deletion or a block substitution of pyrimidines for 6 purines within the HDE abolished all 3'-end processing. Compensatory changes were introduced into a synthetic human U7 gene, whose transcripts assemble into Sm snRNPs in vivo. Suppression of the 6-purine substitution as well as a 3-purine substitution within the HDE was obtained in vivo by coexpressing the corresponding U7 suppressor RNAs and in vitro by using nuclear extracts prepared from HeLa cells containing U7 suppressor genes. Our results not only provide genetic evidence for base-pairing between the U7 snRNP and the HDE of mammalian histone pre-mRNAs but reveal an unexpected tolerance to drastic changes in the nature of the base paired region. PMID- 1885008 TI - Sequences mediating the translation of mouse S16 ribosomal protein mRNA during myoblast differentiation and in vitro and possible control points for the in vitro translation. AB - The translation of ribosomal protein (r-protein) mRNAs is generally inefficient and regulated during the differentiation of mouse myoblasts into fibers. In this discussion we show that the first 31 nucleotides of the S16 r-protein mRNA, when located at the 5' end of the mRNA, are sufficient to impart the translational properties of an r-protein mRNA to the SV-GALK mRNA, which is normally translated efficiently in both myoblasts and fibers. If the same S16 sequences are located within the interior of the 5'-untranslated region of the SV-GALK mRNA, however, they do not impart the translational properties of an r-protein mRNA to the SV GALK mRNA. The translation of mouse r-protein mRNAs was examined in vitro to help elucidate the mechanisms controlling their translation. Mouse r-protein mRNAs are inefficiently translated in rabbit reticulocyte extracts, and the same sequences that mediate their inefficient and regulated translation during myoblast differentiation also mediate their inefficient translation in a position dependent manner in reticulocyte extracts. To determine whether the subpolysomal r-protein mRNAs that are not actively translated in vivo are capable of translation, subpolysomal RNA was translated in reticulocyte extracts. The subpolysomal r-protein mRNAs are just as capable of translation as are polysomal mRNAs. To help identify the initiation factors and/or the steps in the initiation pathway that mediate the inefficient translation of r-protein mRNAs, reticulocyte extracts were supplemented with purified initiation factors. Only eIF-4F, the cap binding complex, and eIF-3, which is involved in subunit dissociation and interacts with eIF-4F during initiation, stimulated the translation of r-protein mRNA. These experiments, along with m7GDP inhibition studies, suggest that eIF-4F and/or eIF-3, or the steps mediated by these factors, mediate the inefficient translation in reticulocyte extracts and raise the possibility that these steps also control the regulated translation of r-protein mRNAs during myoblast differentiation. PMID- 1885009 TI - [Status of microsomal monooxygenases after a single inhalation of sulfur containing gas condensate]. PMID- 1885010 TI - [Complex evaluation of self-purifying capacity of reservoir water]. AB - Self-purification ability of water reservoirs is determined by a complex of indices: ratio of 5-day biochemical consumption of oxygen to full consumption of oxygen; chemical consumption of oxygen, content of dissolved oxygen; ratio of lactose-positive to faecal coli; total specific loading on the water object. Complex assessment of the intensity of self-purification makes it possible to characterize the process as sufficient, insufficient, low, very low. PMID- 1885011 TI - [Sanitary-microbiological studies of oysters and seawater by the coast of the northern Caucasus]. AB - Sanitary-microbiological studies carried out in 1985-1989 in the area of experimental raising of oysters at the northern Caucasus coast of the Black Sea have detected the correlation between the microflora of oysters and the quantitative and qualitative composition of the microflora of marine water, seasonal dynamics of the number of sanitary-indicative, tentatively pathogenic and saprophytic microorganisms of water and the raised oysters. PMID- 1885012 TI - [Hygienic evaluation of concrete made with the use of a super- plasticizer dophen]. PMID- 1885013 TI - [Toxicological and hygienic studies of a new polymer glue to be used in shoe making industry]. AB - Toxico-hygienic studies have been carried out of a new polymeric glue to be used in the shoe-making industry. As a result of studies the use of the glue is recommended in the shoe-making industry, conditions of its safe use and the way to maintain current sanitary supervision have been suggested. PMID- 1885014 TI - [Efficiency of preventive use of bemethyl during long-term voyages]. AB - A positive effect of bemityl in the 24-hour dose of 0.25-0.5 g on the cellular and humoral factors of nonspecific defence, blood neutrophils intracellular exchange, barrier properties of the skin, working ability of operators and on morbidity has been established. An important property of the drug is long duration of preservation of the pharmacological effect, which prevents the development of disadaptation states following the cessation of its use. The data obtained gives the basis to recommend the actoprotective drug bemityl to increase nonspecific resistance during long-term voyages. PMID- 1885015 TI - [Effect of school exercises on the subject of "Visual horizons" on the dynamics of the visual functions in children]. PMID- 1885017 TI - [Protection from radon emissions from a radon laboratory]. AB - An absorbing chuck with activated coal has been suggested for absorbing radon and its daughter products' wastes from the air which are formed in the device YPP-1 in the process of preparation of radon water concentrate. Testing of such a device has shown that it is simple, reliable and efficient in functioning, thus it can be recommended to be used in radon laboratories. PMID- 1885016 TI - [Comparative evaluation of inhalation exposure to plutonium -238 and plutonium 239 nitrates]. PMID- 1885018 TI - [Optimal control of waste water contaminated with radionuclides]. PMID- 1885019 TI - [The role of toxic modifying substances in chemical carcinogenesis]. PMID- 1885020 TI - [Structural and functional evaluation of the adrenal glands in a toxicological experiment]. PMID- 1885021 TI - [Socioeconomic problems of work and health of workers]. PMID- 1885022 TI - [Late toxic effects of chlorophos (review of the literature)]. PMID- 1885023 TI - [Effect of vibration on lipid and mineral metabolism in workers]. PMID- 1885024 TI - [Use of a unified approach to the study of health status of l3-l5 years old schoolchildren in the USSR and Democratic Republic of Germany]. PMID- 1885025 TI - [Interpretation of the results of analysis of pesticide levels in food products]. PMID- 1885026 TI - [A screening method of evaluation of the effect of xenobiotics on the reproductive function]. PMID- 1885027 TI - [Characteristics of using Infusoria culture in toxicological studies]. PMID- 1885028 TI - [Determining the levels of trifumin and the products of its transformation in agricultural cultures, water and soil]. PMID- 1885030 TI - [Concept of control levels and the possibilities of its use in accident emergency radiation-hygienic standardization]. PMID- 1885029 TI - [Chromatographic analysis of organochlorine compounds in water]. PMID- 1885031 TI - [Improving the activities of the journal]. PMID- 1885032 TI - [A method of calculation of threshold and subthreshold levels based on exponential models dose (factor level)-effect]. PMID- 1885033 TI - [Current approach to hygienic evaluation of protective and damaging reactions of the immune system after exposure to environmental factors]. AB - When studying the immune status of the organism the use of additional exposures allow to clear up the defective character of physiological functions even when overt changes are absent. Altitude chamber hypoxia++, reproduction of allergic reactions of the slow and non-slow types, pathogenic Escherichia infection followed by assessment of virulence factors were used as such a stress under exposure to chemicals, electromagnetic fields of radio frequencies. A model was developed for the determination of safe levels of exposure to environmental factors, which makes it possible to differentiate the damaging and defence action of antibodies on the basis of their influence on the fetus and offspring. The effects of antibodies characterized by the postimplantation mortality of fetuses may be used as a criterion of significance for the organism of shifts in immunological reactivity. PMID- 1885034 TI - [Dependence of levels of lead release into the water on the conditions of the use of polyvinylchloride products]. PMID- 1885035 TI - [Sanitary protection of the shore marine water in Alushta]. PMID- 1885036 TI - [Hygienic assessment of arylox to be used in thermal water supply]. PMID- 1885037 TI - [Relationship between soil contamination by toxic industrial waste and health of the population]. AB - The data concerning the effects of the stored toxic industrial wastes on the health of people living in the zone of wastes storing grounds, on their role in ambient air and drinking water contamination is presented. The importance of using low waste and wasteless technologies for the reduction of the amount of toxic wastes to be disinfected is shown using the examples from practice. Measures taken by the sanitary service of Ukraine aimed at environmental protection from contamination by toxic industrial wastes are presented. PMID- 1885038 TI - [A scientific study of maximum allowable concentration of halokon in the water of reservoirs]. PMID- 1885039 TI - [Experimental substantiation of maximum allowable concentration of phosphoric acid in the water of reservoirs]. AB - It has been found out on the basis of experimental studies, that the threshold concentration of phosphorous acid is 85.7 mg/l according to the influence on organoleptic water properties, I mg/l--according to the influence on the sanitary regimen of water reservoirs. The preparation is of low toxicity when administered perorally to laboratory animals, cumulation degree is medium. Embryotoxic and gonadotoxic effects, mutagenic and allergic properties have not been detected. The maximum no-effect dose in the chronic experiment is 1.4 mg/kg. MAC is recommended on the level of I mg/l according to the general sanitary indicator of harmfulness (the 3-d class of danger). PMID- 1885040 TI - [Assessment of the toxic effects of a combination of chemicals contained in the soil]. AB - A technique of the assessment of toxic effect of a combination of chemicals in soil on the organism of mammals has been developed. It is based on the investigation of the damaging effect of components of the combination when they get into the organism through the soil-contiguous media on the level of summary 24-hour doses, as well as when their residues get into the organism with food, water, air and through the skin. A method calculating the threshold dose of each component of the combination in soil according to the toxicological harm index is suggested. PMID- 1885042 TI - [Health-related substantiation of preventive measures for operators of video terminals]. PMID- 1885041 TI - [Health-related properties of polyamines (review)]. PMID- 1885043 TI - [Effects of computer technology and work conditions on health status of workers (review)]. PMID- 1885044 TI - [Assessment of the distribution in the body and the dose on the respiratory tract and organs after single, short-term and long-term inhalation of americium-241]. AB - On the basis of comparison of publications on accidental human intake of americium-241 and animal experimental studies dosimetric characteristics were obtained reflecting the dynamics of accumulation, formation of the dose on the organs and parts of the respiratory tract, as well as of the 24-hour elimination from the organism of the mentioned radionuclide following single, short- and long term administration of americium-241 from the air. Results were obtained with the use of computers for quantitative modelling of the most complete metabolic transport scheme of americium. PMID- 1885045 TI - [New approaches to identification of high risk groups among inhabitants of Moscow]. PMID- 1885046 TI - [Bases of the duration of a chronic experiment]. PMID- 1885047 TI - [Hygienic assessment of the effects of antiseptic preparation cyclimid on the state of barrier-protective properties of the skin]. PMID- 1885048 TI - [Assessment of microbial contamination of several drugs]. PMID- 1885050 TI - [An experimental study of carcinogenic activity of bucide and its effects on the reproductive function]. PMID- 1885049 TI - [Toxic effects of sodium nitrite]. PMID- 1885051 TI - [Effects of different functional groups of phenylurea compounds on indices of their toxicity and MAC in the air of work areas]. AB - Free-Wilson technique with the use of computer correlation-regression and dispersion analysis program made it possible to determine the importance of certain radicals and functional groups for the characteristics of the toxicity of phenylurea compounds. Specific contribution of different functional groups depending on their position in the molecule to the values of toxicometric indices (LD50, Limac, Limch) and MAC of those compounds in the air of the working area were determined. Summary contributions of radicals with their functional groups to the values of toxicity indices and MACs for individual substances of the phenylurea group was calculated. A possibility was shown to use the Free-Wilson technique for the rapid prediction of toxicity and hygienic standards for new phenylurea compounds in the air of the working area. PMID- 1885052 TI - [Effects of pesticides on health (review)]. PMID- 1885053 TI - [Microbiological criteria of the quality of recreational waters in COMECON member countries]. PMID- 1885054 TI - [Study of the quality of drinking water and diseases connected with water]. PMID- 1885055 TI - [60 years of the Sanitary-Hygienic Department of the I. M. Sechenov's Moscow Medical Academy]. PMID- 1885056 TI - [Views of Ibn Sina (Avicenna) on health]. PMID- 1885057 TI - [Gas chromatographic method of determination of treflan in water, soil and food products]. PMID- 1885058 TI - [Rapid determination of thionyl chloride in the air of industrial premises]. PMID- 1885059 TI - [Performance capacity determination in laboratory animals]. PMID- 1885060 TI - [Flash-desorption--an alternative of the existing methods of isolating organic micro-impurities from the sorbents in gas chromatographic analysis of polluted air]. PMID- 1885061 TI - [Hygienic assessment of the use of municipal sewage at a meson plant]. PMID- 1885062 TI - [Maximum allowable concentration--combined, associated and complex action]. PMID- 1885063 TI - Natural history of gastro-oesophageal reflux disease without oesophagitis. AB - This retrospective study was undertaken to characterise the clinical course and reflux pattern of patients with gastro-oesophageal reflux without evidence of oesophagitis. We investigated 33 patients (12 women, 21 men; mean age 36 years) with typical symptoms, a negative oesophagoscopy, and a 24 hour oesophageal pH metry indicative of pathological gastro-oesophageal reflux. All patients received antacids or prokinetic drugs or both for three to six months. Nineteen of 33 patients still had symptoms at the end of treatment, of whom five had developed erosive changes of the oesophageal mucosa. The other 14 discontinued treatment and remained asymptomatic during a six month follow up period. Comparison of the pretreatment pH-metry data of the 19 symptomatic patients and the 14 asymptomatic patients showed no differences in the pattern of gastro-oesophageal reflux in the two groups. We conclude that in a substantial proportion of patients with pathological reflux without oesophagitis symptoms may persist and mucosal lesions may develop during conventional treatment without any apparent change in the reflux. Patients who developed endoscopic oesophagitis did not have a more severe pretreatment pattern of gastro-oesophageal reflux when compared with those who did not develop oesophageal mucosal damage. PMID- 1885065 TI - Neutrophil activation by Helicobacter pylori. AB - Helicobacter pylori infection of the stomach is accompanied by a persistent polymorphonuclear leukocyte (PMNL) infiltrate of the mucosa. The aim of this work was to study the activation of human PMNL by substances produced by H pylori. Filtered H pylori conditioned media stimulated a significant PMNL oxidative burst (p less than 0.002). This was equal to 26% of the maximal response stimulated by the PMNL chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP, 1 mumol/l). The response to FMLP was prolonged by the combined presence of complement inactivated human anti-H pylori plasma and conditioned medium (p less than 0.002). High pressure liquid chromatography of an extract of conditioned medium showed a fraction that stimulated PMNL, eluted, and antigenically cross reacted with FMLP. Washed H pylori cells, and those opsonised with complement inactivated human anti-H pylori plasma, did not induce a significant oxidative burst. Opsonized H pylori, however, prolonged the oxidative burst induced by FMLP (p less than 0.02). In conclusion, H pylori synthesizes and secretes a substance, probably FMLP, that may account for the PMNL accumulation that accompanies H pylori infections. Immune complexes composed of H pylori antigen and specific antibody potentiate the PMNL oxidative burst. This combination of H pylori derived products, and host PMNL and antibodies, may be involved in the mucosal damage observed in H pylori associated gastritis. PMID- 1885064 TI - Serum pepsinogen I concentrations in peptic ulcer patients in relation to ulcer location and stage. AB - To investigate the relation of the serum group I pepsinogen (PG I) concentration to the location of gastric ulcers and chronicity of peptic ulcers, ulcer patients (n = 322) were compared with endoscopically normal subjects (n = 174). The mean PG I concentration was significantly higher in male control subjects (n = 90) than in female control subjects (n = 84). In male patients with ulcers in the duodenum (n = 69), antrum (n = 34), or angulus portion (the lower third of the body; n = 83), the mean serum PG I concentration was significantly higher than in the control subjects but in patients with an ulcer in the upper body (n = 49) it was similar to control values. Men with active or healing ulcers (n = 149) showed a significantly higher serum PG I concentration than those with scarred lesions (n = 86) when the abnormality was located in either the upper body or in the angulus portion. For female patients (n = 87), the results were similar. These results suggest that serum PG I concentrations reflect the stages of activity of peptic ulcer. PMID- 1885066 TI - Different types of peroxisomes in human duodenal epithelium. AB - Peroxisomes are ubiquitous organelles containing enzyme sequences for beta oxidation of fatty acids, synthesis of bile acids, and ether phospholipids. In the inherited peroxisomal diseases one or more enzymes are deficient in hepatic, renal, and fibroblast peroxisomes. We have examined peroxisomes by light and electron microscopy in 29 duodenal biopsy specimens (21 with normal mucosa) after staining for catalase activity, a marker enzyme. Peroxisomes were most numerous in the apices of the nucleus and at the villus base. Two types were distinguished: rounded to oval forms with a median lesser diameter of 0.23-0.31 microns, and tubular, vermiform organelles 0.1 microns thick and up to 3 microns long. Both types coexist in most patients. Tilting of sections and examination of semithin sections at 120 kV did not show connections between individual organelles. By morphometry, volume density was at least 0.45-0.62% of cellular volume, compared to 1.05% in human liver. In contrast, in four out of five individuals surface density of the peroxisomal membrane was 1.4-2.3 times higher than in control livers; this is expected to favour the exchange of metabolites. We suggest that intestinal peroxisomes contribute substantially to the breakdown of very long chain fatty acids. PMID- 1885067 TI - Effect of inhibition of Helicobacter pylori urease activity by acetohydroxamic acid on serum gastrin in duodenal ulcer subjects. AB - The mechanism of the hypergastrinaemia associated with Helicobacter pylori infection is unknown. It may be an effect of the ammonia produced by the bacterium near the antral epithelial surface. We have examined the effect on serum gastrin of inhibiting H pylori urease activity with acetohydroxamic acid in six duodenal ulcer patients. On day 1 the fasted patients received placebo tablets at 8 am, a peptide meal at 10 am, and a 14C urea breath test at 11.30 am. The next day 750 mg acetohydroxamic acid was administered orally in place of the placebo. The median (range) 30 minute breath test value (dose/mmol CO2 X kg body wt X 100) was 152 (111-335) on day 1, but only 22 (14-95) the next day (p less than 0.03). Further studies performed in one subject confirmed that acetohydroxamic acid lowered the ammonium concentration and raised the urea concentration in gastric juice. The inhibition of urease activity and ammonia production did not result in a fall in the basal gastrin concentration or in the median integrated gastrin response to the peptide meal, which was 78 ng/1.h (range 21-222) on day 1 and 79 ng/1.h (33-207) the next day. Ten days after acetohydroxamic acid, the urea breath test values were similar to those before treatment. This study shows that the raised gastrin concentration in patients with H pylori infection is not directly related to the organism's urease activity. It also shows that temporary suppression of H pylori urease activity does not clear the infection. PMID- 1885068 TI - Animal model of gluten induced enteropathy in mice. AB - The aim of our experiments was to produce a local T cell mediated immune response to gliadin in the mouse small intestine as a possible animal model of gluten sensitive enteropathy, coeliac disease. BALB/c and BDF1 mice were immunised systemically with gliadin in complete Freund's adjuvant. The jejunal mucosa was challenged by feeding a gluten containing diet, and villus and crypt lengths, crypt cell production rate, and intraepithelial lymphocyte counts were determined to assess mucosal cell mediated immunity. In some animals permeability and local immunity were modulated by concurrent intestinal anaphylaxis or a graft versus host reaction. There were no changes in the jejunal mucosa of BALB/c mice fed a gluten containing diet after having been parenterally immunized. When, however, mice were parenterally immunised with gliadin, fed a gluten containing diet, rendered hypersensitive to helminth antigen by infection with the nematode parasite Nippostrongylus brasiliensis, and challenged intravenously to produce intestinal anaphylaxis crypt cell production rate was significantly higher than in ovalbumin immunized controls at 12 days after parasite challenge. Finally, graft versus host reaction was induced in BDF1 mice that had been parenterally immunised with gliadin and were on a gluten containing diet. Two weeks later these mice had significantly longer crypts and a higher crypt cell production rate and intraepithelial lymphocyte count than control, unimmunized mice with graft versus host reaction. We conclude that active immunization with gliadin does not in itself produce intestinal cell mediated immunity to gliadin contained in the diet, or enteropathy. Additional factors, such as those occurring during intestinal anaphylaxis (increase intestinal permeability), or during graft versus host reaction (enhanced antigen presentation), seem to be necessary for the full expression of a jejunal mucosal reaction. PMID- 1885069 TI - Fc receptor function and circulating immune complexes in gluten sensitive enteropathy--possible significance of serum IgA. AB - The capacity to clear IgG containing immune complexes from the circulation was studied in patients with coeliac disease (n = 13), dermatitis herpetiformis (n = 8), and coeliac disease with concomitant serum IgA deficiency (n = 4). A small group of patients with active ulcerative colitis (n = 4) was included as a bowel disease control group. Clearance was estimated by measuring the disappearance rate of a bolus dose of intravenously injected IgG coated autologous erythrocytes. The mean T1/2 of clearance was prolonged in both coeliac disease (86 (24) minutes) and dermatitis herpetiformis (111 (35) minutes), compared with healthy subjects (20 (5) minutes) and coeliac patients with concomitant serum IgA deficiency (T1/2 = 17 (6) minutes). Patients with ulcerative colitis had a prolonged clearance, with a T1/2 of 195 (63) minutes. Values of circulating immune complexes were measured by four assays; C1q binding and C3, IgG, and IgA containing immune complexes. C1q binding immune complexes were detected only in IgA deficient gluten sensitive enteropathy. Patients with coeliac disease and dermatitis herpetiformis had higher values of C3, IgG, and IgA containing immune complexes than control subjects and serum IgA deficient patients with coeliac disease. The clearance rate was inversely correlated to the amount of immune complexes for the subgroups of gluten sensitive enteropathy. PMID- 1885070 TI - Compliance of adolescents with coeliac disease with a gluten free diet. AB - A cohort of 123 patients with coeliac disease, diagnosed in the first three years of life and followed up for at least 10 years, was reevaluated during the teenage period in terms of compliance with the diet and clinical state. Mucosal structure and lymphocytes were assessed in small intestinal biopsy specimens obtained from 36 subjects, by computerised image analysis. Of these adolescents with coeliac disease, 65% were adhering to a strict gluten free diet, 11.4% were on a gluten free diet but with occasional gluten intake, and 23.6% were on a gluten containing diet. Clinical symptoms occurred more frequently in patients on a gluten containing diet, but not in patients on a semi-strict diet. Occasional intake of small amounts (0.06-2 g/day) of gluten did not produce increased concentrations of antigliadin antibodies but resulted in an appreciably increased crypt epithelial volume and expanded crypt intraepithelial lymphocyte population. PMID- 1885071 TI - Pathological effects of Phaseolus vulgaris isolectins on pig jejunal mucosa in organ culture. AB - The interaction of plant lectins with pig small intestinal epithelium in organ culture was studied. The binding of Phaseolus vulgaris (PHA) isolectins E4 and L4 to the microvilli and microvillus vesicles in the top area of the villi was shown by immunoelectron microscopy. Differences were observed in the distribution of the isolectins. In the explants cultured for five hours with the PHA isolectins, the enterocyte height and the villus length were decreased, and a lower villus: crypt ratio was calculated. Ultrastructurally, the microvilli were shorter and irregularly positioned. After incubation with both PHA E4 and PHA L4, clusters of small vesicles, tied off from the microvilli, were seen in higher numbers when compared with control explants. The activity of the brush border enzyme sucrase isomaltase was reduced in the PHA E4 incubated explants but did not change in the PHA L4 incubated explants. This investigation shows that explants of pig jejunal mucosa in organ culture are suitable for study of the pathological effects of lectins on the small intestinal mucosa. This method may also be used in elucidating the mechanisms by which damage to mucosal structure occurs. PMID- 1885072 TI - Carcinoma and DNA aneuploidy in Crohn's colitis--a histological and flow cytometric study. AB - Twenty four patients with longstanding colonic Crohn's disease were examined prospectively with colonoscopy and multiple biopsy sampling in order to detect histological dysplasia or abnormal aneuploid DNA content, or both. Biopsy specimens were taken from 10 predetermined locations in the colon and rectum. No patient had definite dysplasia but three displayed DNA aneuploidy (12.5%), and one of these subsequently developed a carcinoma (Dukes' C at operation) in the ascending colon. No concomitant dysplasia was detected but the carcinoma as well as other parts of the mucosa were DNA aneuploid. It is concluded that dysplasia is rare in patients with Crohn's colitis, but findings of DNA aneuploidy warrant vigilance in follow up as this may indicate impending carcinoma. Further prospective studies are needed before the predictive value of DNA aneuploidy can be determined and before general recommendations of colonoscopic surveillance, as in longstanding ulcerative colitis, can be made. PMID- 1885074 TI - Coexpression of CD4 and CD8 on peripheral blood T cells and lamina propria T cells in inflammatory bowel disease by two colour immunofluorescence and flow cytometric analysis. AB - Using two colour immunofluorescence with fluorescein isothiocyanate and phycoerythrin labelled monoclonal antibodies and multiparameter flow cytometry, we investigated the coexpression of CD4 and CD8 antigens on peripheral blood lymphocytes and lamina propria lymphocytes of patients with ulcerative colitis and Crohn's disease and normal control subjects. Both the absolute number and the proportion of peripheral blood CD4+, CD8+ cells in inflammatory bowel disease were small but significantly increased compared with those in normal control subjects. Peripheral blood lymphocytes activated with phytohaemagglutinin showed appreciably increased coexpression of CD4+, CD8+. These CD4, CD8 positive cells were large and granular. Thus the increased number of peripheral blood CD4+, CD8+ cells in inflammatory bowel disease suggests that chronic immune activation occurs not only in the active state of the disease but also in remission. The proportion of CD4+, CD8+ cells in the lamina propria was greater than in peripheral blood in normal subjects, suggesting chronic immune stimulation of the local immune system. This was also seen in patients with Crohn's disease or inactive ulcerative colitis. The proportion of CD4+, CD8+ cells was, however, significantly less in the lamina propria of patients with active ulcerative colitis. Whether this implies a possible defect in mucosal immunoregulation in active ulcerative colitis cannot be determined from these results. PMID- 1885073 TI - Serum concentrations of tumour necrosis factor alpha in childhood chronic inflammatory bowel disease. AB - Serum tumour necrosis factor alpha (TNF alpha) concentrations were measured by enzyme linked immunoadsorbent assay in 31 normal children and during 65 episodes of clinical remission and 54 episodes of relapse in 92 children with chronic inflammatory bowel disease. An appreciable rise in TNF alpha was found only in children in relapse of ulcerative colitis and colonic Crohn's disease. The group of children with small bowel Crohn's disease in relapse did not show increases of TNF alpha above control concentrations, despite an equivalent rise in disease indices. Height velocity was depressed in children with relapse of large bowel Crohn's disease and ulcerative colitis compared with the equivalent condition in remission. The impairment of growth velocity was significantly greater in relapse of large bowel Crohn's disease and ulcerative colitis than in small bowel Crohn's disease alone, although for the subgroups in stage 1 puberty (prepubertal) the differences were not significant. Inadequate growth in chronic inflammatory bowel disease is currently ascribed to inadequate nutrition and TNF alpha may contribute to this through its cachexia inducing effects. It may, in addition, diminish pituitary growth hormone release. These results suggest that production of TNF alpha may be associated with growth failure in relapse of colonic inflammatory bowel disease. PMID- 1885075 TI - Optimum dosage of 5-aminosalicylic acid as rectal enemas in patients with active ulcerative colitis. AB - 5-Aminosalicylic acid (5-ASA), the active moiety of sulphasalazine (SASP), was given as a rectal enema to patients with mild to moderate distal ulcerative colitis to determine the minimum effective dosage. A double blind study was carried out using enemas containing 1, 2, or 4 g or 5-ASA or placebo for a one month treatment period. One hundred and thirteen patients with ulcerative colitis attending our outpatient clinic volunteered to participate. Clinical, sigmoidoscopic, and histological assessments were carried out at the beginning of the study and after 15 and 30 days of treatment. All patients who received 5-ASA enemas showed significantly better results than those who received a placebo enema (p less than 0.001) but no difference was detected among the patients receiving differing concentrations of 5-ASA. This study suggests that 1 g 5-ASA (in a 100 ml enema) is a sufficient dosage for patients with a mild to moderate attack of ulcerative colitis. PMID- 1885076 TI - Segmental variability of glucocorticoid induced electrolyte transport in rat colon. AB - Recent studies suggest that the ability of glucocorticoids to reduce diarrhoea in active colitis may reflect their direct effects on distal colonic electrogenic Na+ transport and water absorption, as well as their anti-inflammatory action. To determine whether glucocorticoids induce similar changes in proximal colon, specific Na+ and K+ channel blockers (amiloride and tetraethylammonium chloride (TEA) respectively) were used to evaluate the cation transport properties of rat proximal and distal colon in vitro after three days treatment with the glucocorticoid agonist dexamethasone (600 micrograms/100 g/day). In the proximal colon, dexamethasone increased short circuit current (Isc) 2.3 fold (p less than 0.025) and total conductance (Gt) by 87% (p less than 0.015), but had negligible effects on the maximum activity of the basolateral membrane Na(+)-K+ pump and the baseline Na+ and K+ conductive properties of the apical membrane. Additional studies with diphenylamine-2-carboxylic acid (a Cl- channel blocker) suggested that the dexamethasone induced increases in Isc and Gt in proximal colon reflected stimulation of an electrogenic Cl- secretory process. In contrast, in the distal colon dexamethasone increased Isc 10 fold (p less than 0.025), Gt by 100% (p less than 0.015), and the maximum activity of the basolateral Na(+)-K+ pump by 200% (p less than 0.05), and induced substantial Na+ and K+ conductances in the apical membrane. These results indicate that dexamethasone stimulates electrogenic Na+ transport and water absorption to a significant degree only in the distal segment of rat colon. Thus in patients with active colitis, that part of the antidiarrhoeal action of glucocorticoids that reflects stimulation of electrogenic Na+ transport (and hence water absorption) may be restricted to the descending colon and rectum. PMID- 1885078 TI - Alpha 1 antitrypsin phenotypes and alcoholic pancreatitis. AB - Altered frequencies of alpha 1 antitrypsin phenotypes have been reported in patients with chronic pancreatitis, suggesting a possible genetic basis for individual susceptibility to this disease. Alpha 1 antitrypsin phenotypes, with particular regard to alcoholic pancreatitis, were studied. Patients with alcoholic pancreatitis were compared with alcoholic control subjects with no history of pancreatic disease. Serum alpha 1 antitrypsin concentrations were raised in pancreatitis patients sampled within one month of an acute attack of pancreatitis, but otherwise values were similar to those of control subjects. There were no significant differences in alpha 1 antitrypsin phenotypes between alcoholics with pancreatitis and alcoholic control subjects. This study of alpha 1 antitrypsin phenotypes provides no evidence of an inherited susceptibility to alcoholic pancreatitis. PMID- 1885077 TI - Effect of moderate exercise on bowel habit. AB - Ten healthy volunteers (six men and four women, aged 22-41 years) were studied in a crossover trial. The study was divided into three one week periods. During each period the subjects either ran on a treadmill, cycled on a bicycle ergometer, or rested in a chair for 1 hour every day. The exercise was performed at two thirds predicted maximum heart rate (equivalent to 50% VO2 max). The sequences were rotated; no studies were performed in the perimenstrual period. Transit was measured by the method of measuring the excretion of a single dose of radio opaque markers; all stools were collected, weighed, and x rayed after the ingestion of radio-opaque markers. Dietary fibre and fluid intake were measured on the fourth day of each test period by 24 hour record. Lifestyle was otherwise unchanged. Transit time was dramatically accelerated by moderate exercise (both jogging and cycling); however, stool weight, defecation frequency, dietary fibre intake, and fluid intake did not change significantly. Whole gut transit changed from 51.2 hours (95% confidence intervals 41.9 to 60.5) at rest to 36.6 hours (31.6 to 39.2) when riding and 34.0 hours (28.8 to 39.2) when jogging. Riding and running both differed significantly from resting (p less than 0.01); the difference between riding and running was not significant. PMID- 1885079 TI - Proliferative activity of neuroendocrine tumours of the gastroenteropancreatic endocrine system: DNA flow cytometric and immunohistological investigations. AB - The proliferative activity of 16 tumour specimens from 13 patients with neuroendocrine tumours of the gastroenteropancreatic endocrine system was studied by DNA flow cytometry and immunohistology for the nuclear Ki67 proliferation antigen. Equivalent results were obtained with both methods, which showed the proliferative activity of gastroenteropancreatic neuroendocrine tumours to be heterogeneous. In four malignant small intestinal carcinoids and one extravisceral carcinoid localised in the retroperitoneum the percentage (index) of proliferating tumour cells as measured by DNA flow cytometry ranged from 2.9 to 36.2% corresponding to low, moderate, or high proliferative activity. In four malignant pancreatic endocrine tumours and their metastases indices ranged from 8.7 to 18.3%, corresponding to low, moderate, or high proliferative activity. In four benign pancreatic endocrine tumours indices ranged from 4.3 to 7.7%, all corresponding to low proliferative activity. This heterogeneity of proliferative activity may in part explain the heterogeneous results reported of chemotherapy treatment. As chemotherapy of tumours is largely affected by favourable cell cycling kinetics, individual diagnostic investigations of the proliferative activity of these neuroendocrine tumours may be of value for identifying patients suitable for this treatment. PMID- 1885080 TI - Gastric antral vascular ectasia: a problem of recognition and diagnosis. AB - Gastric antral vascular ectasia ('water melon stomach') is a poorly documented cause of occult upper gastrointestinal blood loss. We describe a case which emphasises the clinical and pathological difficulties that can be encountered in making this elusive diagnosis. PMID- 1885081 TI - Acute gall bladder perforation--a dilemma in early diagnosis. AB - Gall bladder perforation is a rare complication of cholecystitis. A definitive diagnosis is uncommon before surgery and the morbidity and mortality associated with this condition are high. We report six patients with gall bladder perforation to show the difficulty of making an early diagnosis. The history and the clinical findings of these patients are reviewed to highlight diagnostic pitfalls. PMID- 1885083 TI - Ranitidine and non-steroidal anti-inflammatory drug (NSAID) associated gastric and duodenal ulcers. PMID- 1885082 TI - Hodgkin's disease presenting as liver abscesses. AB - A patient is reported who presented with sterile hepatic abscesses which proved to be the first manifestation of Hodgkin's disease. He failed to improve with antibiotic treatment but responded to combined chemotherapy. Liver involvement as the first sign of Hodgkin's disease is rare. Liver abscesses due to Hodgkin's disease seem to be previously unreported. PMID- 1885084 TI - Case of watermelon stomach successfully treated by heat probe electrocoagulation. PMID- 1885085 TI - Risk evaluation in a small series of transabdominal chorionic villus sampling. AB - Previous reports have suggested that the fetal loss rate with transcervical chorionic villus sampling was high in the initial 100-300 procedures performed. In a consecutive series of 155 patients with first-trimester transabdominal chorionic villus sampling (CVS), we observed a total fetal loss rate of 8.4%, and loss rate not attributable to induced abortion or cytogenetic abnormality of 3.2%. Our results demonstrate that transabdominal CVS in the first trimester of pregnancy is a safe method of prenatal diagnosis. PMID- 1885086 TI - Computer analysis of the antepartum fetal heart rate patterns in the intrauterine growth-retarded human fetus using Sonicaid System 8000. AB - A total of 28 pregnant women with growth-retarded fetuses were studied to examine the antepartum fetal heart rate patterns between 30 and 39 weeks of gestation. Sonicaid Computer System 8000 was used to analyze on line 200 cardiotocograms. We found that there is an increase in the number of accelerations, an increase in variation assessed in beats per minute and in milliseconds, an increase in duration of high episode and a decrease in the number of decelerations. PMID- 1885087 TI - Incidence of spontaneous and evoked fetal movements in the first half of twin pregnancy. AB - Fetal movements (FM) may be spontaneous, originating in the fetus itself, or evoked, caused by external stimuli. The FM in 21 normal twin pregnancies at 10 and 21 weeks of gestation were studied. The percentage rate of evoked FM which occur simultaneously in both twins was 4.96% of all observed FM. The rate of the spontaneous FM which occur independently in each fetus was 95.04% of all FM. The low incidence of evoked FM, at an early gestational age (10-21 weeks) emphasizes the ability of these young fetuses to perceive external stimuli and to react to them by FM. PMID- 1885088 TI - Changes in electromyographic activity of the cervix after stimulation of labour with oxytocin. AB - The electrical activity of the cervix can be measured during labour. The influence of oxytocin on electromyographic (EMG) activity of the cervical musculature was studied in 80 primiparous women after induction of labor. The highest electrical activity registered at the time of uterine contraction and between two contractions was used for analysis. The basic pattern of oxytocin produced changes in muscular contractions in the cervix observed via EMG activity is that of the activity increasing with contractions of the uterine corpus and diminishing between contractions. The effect of oxytocin on cervical musculature is different in ripe and unripe cervices. PMID- 1885089 TI - Vasoactive effects of intra- and extravascular serotonin, PGE2 and PGF2 alpha in human umbilical arteries. AB - The effect of serotonin, PGE2 and PGF2 alpha on the vascular tension in human umbilical arteries has been investigated during in vitro perfusions. All autacoids induced dose-dependent biphasic pressure responses when added to the perfusate. When added to the extraumbilical fluid, serotonin induced monophasic vasoconstrictory responses, whereas PGE2 and PGF2 alpha did not elicit significant changes except for minor pressure oscillations in some experiments. The results obtained suggest a contributory role of the endothelial layer in the action of these autacoids on the smooth muscle tension. PMID- 1885090 TI - Advantage or disadvantage of episiotomy compared with spontaneous perineal laceration. AB - In a prospective clinical investigation of 2,144 deliveries, we elucidate the indications for episiotomy and how different methods of anesthesia affect the frequency of episiotomy and the perineal problems after episiotomy compared with those after spontaneous perineal laceration. We found a significantly higher infection rate (p less than 0.001) and a longer healing period in the episiotomy group. These differences remain even if only primigravida or the indication, imminent perineal laceration, is studied. The results indicate that many women will unnecessarily suffer after an episiotomy. The patient's subjective problems are significantly increased, both immediately and at the 3-month postoperative follow-up. PMID- 1885091 TI - Relationship of fetal breathing movement pattern to surfactant phospholipid levels in amniotic fluid and postnatal respiratory complications. AB - Fetal breathing patterns in 102 patients delivering before 37 weeks of gestation were divided into three types by the duration of successive respiratory activity using an ultrasonic scanner. Approximately 80% of the fetuses with fetal breathing absent or less than 9 s developed neonatal respiratory complications, including 11 cases of severe RDS and 8 cases of apnea of prematurity. However, no infant showing breathing activity of 30 s or more in utero experienced severe respiratory complications after birth. Furthermore, the surfactant phospholipid concentration in amniotic fluid was significantly increased with prolongation of successive fetal breathing activity. These results suggest that the duration of successive fetal breathing movements closely relates with fetal lung development including biochemical and neuromuscular systems in the humans, i.e. functional maturation of the fetal respiratory system, and also that prenatal analysis of breathing patterns may permit evaluation of pulmonary functional capacity after birth. PMID- 1885092 TI - Levels of glucose and insulin during twenty-four hours in hyperprolactinemic women with pituitary microadenoma. AB - Excursions of plasma glucose and insulin throughout the 24-hour metabolic clock were evaluated in hyperprolactinemic women with pituitary microadenoma. The glucose response to food intake and 24-hour excursion of plasma glucose were not altered in hyperprolactinemic women compared to normal women. Premeal and 24-hour insulin levels were significantly increased in hyperprolactinemic women, though fasting insulin levels were not. Postprandial insulin increments appeared to be more sustained in these patients compared to normal women, though the difference was not statistically significant. And therefore the increased 24-hour concentration of insulin in hyperprolactinemic women appears to be due to the sustained insulin response to meals and increased premeal insulin levels. A slight resistance to insulin was observed in hyperprolactinemic women. That the 24-hour excursion of plasma glucose is not altered in hyperprolactinemic women in the face of decreased sensitivity to insulin may be accounted for by the increased insulin secretion. PMID- 1885093 TI - Ultrasonic validation of residual bladder volume in postvaginal hysterectomy patients. AB - Transverse and sagittal bladder diameters were measured with real-time ultrasound in 80 patients (100 measurements) during the first 2 days of postvaginal hysterectomy to assess the residual bladder volume and compared with the catheterization volume for the same patients. The sonographic method, with a 97.7% specificity and a negative predictive value of 89.5%, proved to be specific enough to eliminate the necessity of routine catheterization for measuring residual bladder volumes of greater than or equal to 150 cm3, thus decreasing the incidence of some major postoperative complications that can occur due to unnecessary catheterization. PMID- 1885094 TI - Trimethoprim and sulfamethoxazole transfer in the in vitro perfused human cotyledon. AB - Utilizing the in vitro human placental model, we studied the placental transfer of trimethoprim and sulfamethoxazole. At trimethoprim concentrations of 7.2 micrograms/ml, only 1.4 micrograms/ml was transported across the placenta after 1 h, and at concentrations of 1.0 microgram/ml, one half the usual serum level, only 0.08 microgram/ml was transported across the placenta. Maternal concentrations of sulfamethoxazole of 29.6 and 127.7 micrograms/ml resulted in concentrations of 5.1 and 14.8 micrograms/ml on the fetal side, respectively. Thus, it would appear that trimethoprim is slowly transported across the placenta and in low concentrations whereas sulfamethoxazole readily crosses the placenta. The combination of these drugs is useful for treatment of bacteriuria. It may also prove to be especially useful for Pneumocystis carinii infections in pregnant women with AIDS. With a half-life of 13 h for trimethoprim and 6 h for sulfamethoxazole, the drugs are not likely to achieve toxic levels in the fetal compartment. Thus, it would appear that trimethoprim and sulfamethoxazole may be both efficacious and safe for the treatment of both these infections during pregnancy. PMID- 1885095 TI - Transvaginal color and pulsed Doppler ultrasound evidence of hemodynamics of the female pelvis. AB - Transvaginal color and pulsed Doppler ultrasound examinations were made on 40 patients to assess hemodynamics in the pelvis. Use of a special probe for transvaginal scanning led to superb simultaneous visualization of structures and blood flow, and we noted various events, even in the small, deep and/or peripheral vessels. Some but not all of the observations were in agreement with the results obtained using transabdominal color and pulsed Doppler ultrasound. We propose that transvaginal color and pulsed Doppler ultrasound be considered for routine use to determine physiological and pathological events in the female pelvis. PMID- 1885096 TI - [Fetal echocardiography]. AB - Fetal echocardiography is an ultrasonic technique for the diagnosis of cardiac defects and fetal arrhythmias. During 1981-1990 we examined 1800 women referred for elective examinations from all over the country. Most, at high risk for fetal cardiac anomalies, were examined in the 22nd week of gestation. Others were examined whenever a fetal arrhythmia or a cardiac defect was suspected. In 251 fetuses (13.9%) pathological cardiac conditions were found, and structural heart defects in 51 (2.8%). When a cardiac defect with poor prognosis was diagnosed during the 2nd trimester, termination of pregnancy was suggested. In 35% of these cases termination of pregnancy was accepted. In 12% of the women examined spontaneous intra-uterine fetal death had occurred, while in 52% live babies were born, but half died within 6 months. In 215 fetuses (11.9%) a cardiac arrhythmia was found, which in 73% consisted of supraventricular premature beats. In 15.8% the fetus was endangered by the arrhythmia, mainly supraventricular tachycardia, atrial fibrillation or atrial flutter. Treatment was by drugs administered to the mother. In 1 case of complete A-V block echocardiographic follow-up demonstrated rapid deterioration of heart function. Delivery was induced and a pacemaker was implanted in the newborn. PMID- 1885097 TI - [Fetal heart rate monitoring in ambulatory and resting mothers]. AB - The nonstress test (NST) to assess fetal wellbeing is done over the course of 30 minutes with the patient lying in the semi-Fowler position. The test relates changes in fetal heart rate to fetal movement, and uterine contractions are also recorded. The purpose of this study was to determine whether the NST is affected by maternal ambulation, so that the patient must be lying down when it is performed. We did the NST during ambulation as well as with the patient reclining. There were no differences in fetal heart rate and/or uterine activity between the 2 tests. 50% of the women preferred the ambulatory method while 25% preferred reclining and 25% expressed no preference. We conclude, that the ambulatory NST is an acceptable alternative to the conventional test with the patient reclining. PMID- 1885098 TI - [Utilization of emergency services in primary care clinics]. AB - Utilization of emergency services (ES) by primary care physicians was retrospectively surveyed in a regional hospital. Referrals and self-referrals from an urban university clinic, a community clinic, a smalltown clinic and a rural community clinic were included. There was an average referral and self referral rate of 38/100/year. Both referrals and proportion of self-referrals were inversely related to the distance between primary care clinic and the ES. Most referrals and self-referrals occurred on week-days during the hours primary care clinics were open. About 13% of ES visits resulted in hospitalization, with no significant differences between the different types of clinic or the hour of referral. We conclude, that hospital-based ES are utilized not only to provide emergency care, but also as support systems for primary care clinics, especially those readily accessible to the ES. PMID- 1885099 TI - [Simultaneous aortic and renal revascularization in chronic renal artery occlusion]. AB - The decision to revascularize an occluded main renal artery is often extremely difficult, especially when aortic and renal occlusive disease co-exist. The main objectives of surgery are preservation of renal parenchyma and possible amelioration of renovascular hypertension, provided the patient's condition permits. In a 52-year-old man with renovascular hypertension and intermittent claudication transfemoral aortography revealed severe atheromatosis of the aorta and iliac arteries. There was total occlusion of the left main renal artery, but the right renal artery was patent. Aorto-femoral bypass was performed using a bifurcated graft. The left kidney was revascularized using an 8-mm straight graft anastomosed end-to-end with the renal artery and the other end was inserted into the distal part of the bifurcated graft, constituting a triple bypass. The postoperative course was uneventful, blood pressure decreased and renal scan showed good left renal function. 6 months later aorto-bifemoral and renal bypass grafts were fully patent. PMID- 1885100 TI - [Neuropsychiatric symptoms in systemic lupus erythematosus]. AB - Involvement of the central nervous system in systemic lupus erythematosus is frequent (50-66%). Its manifestations may be either neurological, psychiatric or both. The psychiatric syndrome may appear without physical symptoms, or may accompany severe systemic involvement. In either case psychiatric diagnosis is quite difficult and consequently treatment is often controversial. We review current knowledge and present the case of an 18-year-old male which illustrates the complexity of both diagnosis and treatment of the syndrome. PMID- 1885101 TI - [Sarcoidosis presenting with subcutaneous nodules]. AB - Sarcoidosis is an uncommon disease with many types of presentation. A 32-year-old woman is described in whom subcutaneous nodules were the presenting symptom. This presentation is vary rare; the differential diagnosis includes rheumatic fever, rheumatoid arthritis, systemic lupus erythematosus and fungal infections. PMID- 1885102 TI - [Vasculitis with cutaneous necrosis induced by oral contraceptive]. AB - Multiple ulcerated and necrotic lesions developed in a 29-year-old woman. Response to treatment during the next few months was minimal. The most plausible explanation was drug-induced vasculitis caused by contraceptive pills (Microgynon: levonorgestrel 0.15 mg and ethinyl oestradiol 0.03 mg). The diagnosis of vasculitis was confirmed by histopathological and immunofluorescent studies. Urticarial manifestations had developed into necrotizing inflammation and the lesions only began to heal after discontinuation of the pills. Contraceptive pills are not included among the drugs causing necrotizing vasculitis, and to the best of our knowledge, this is the first report. Although contraceptive pills are commonly implicated in the induction of erythema nodusom or vasculitis, such a severe reaction with necrosis is rare. PMID- 1885104 TI - [Response to stress and the immunological system]. PMID- 1885103 TI - [Myocardial and central nervous system involvement in scorpion envenomation by Androctonus bicolor bicolor]. AB - A 3-year-old girl was stung by a scorpion (Androctonus bicolor bicolor) in her foot while walking barefoot in a courtyard in the early evening. Within an hour she began to vomit and became extremely agitated. On admission she was stuporous and hypotensive, and severe hypertonicity and prolonged convulsions ensued. Treatment consisted of adrenalin, corticosteroids, diazepam, chloral hydrate and phenobarbital and she improved within 2 hours. The following day myocardial involvement, with tachycardia, gallop rhythm and electrocardiographic abnormalities developed and treatment with digoxin and dexamethasone was started. Full recovery took 6 days. Both black and brown scorpions of this species are dangerous and may cause multisystem manifestations, especially in young children. Usually found in the desert or in sand dunes, it sometimes occurs in inhabited areas as well, in rubble or building ruins. Its distribution is from Haifa in the north down to the Sinai peninsula. PMID- 1885105 TI - [Mental state in old age psychiatry: toward a valid and comprehensive examination]. PMID- 1885106 TI - [Gastrointestinal complications in end-stage renal failure]. PMID- 1885107 TI - [Nonpalpable breast lesions: new aspects of early detection and reduction of mortality in breast cancer]. PMID- 1885108 TI - [Endemic diseases in Lebanon (II): Iodine deficiency]. PMID- 1885109 TI - [The vanishing fetus]. PMID- 1885110 TI - [The treatment of central anticholinergic syndrome and psychotomimetic drug intoxication]. PMID- 1885112 TI - [Narcolepsy in children]. PMID- 1885111 TI - [von Willebrand factor and von Willebrand's disease]. PMID- 1885113 TI - Comparative analyses of age- and sex-specific patterns of vocal behaviour in four species of Old World monkeys. AB - Sound recordings and behavioural data were collected from four primate species of two genera (Macaca, Presbytis). Comparative analyses of structural and behavioural aspects of vocal communication revealed a high degree of intrageneric similarity but striking intergeneric differences. In the two macaque species (Macaca silenus, Macaca radiata), males and females shared the major part of the repertoire. In contrast, in the two langurs (Presbytis johnii, Presbytis entellus), many calls were exclusive to adult males. Striking differences between both species groups occurred with respect to age-specific patterns of vocal behaviour. The diversity of vocal behaviour was assessed from the number of different calls used and the proportion of each call in relation to total vocal output for a given age/sex class. In Macaca, diversity decreases with the age of the vocalizer, whereas in Presbytis the age of the vocalizer and the diversity of vocal behaviour are positively correlated. A comparison of the data of the two genera does not suggest any causal relationship between group composition (e.g. multi-male vs. one-male group) and communication system. Within each genus, interspecific differences in vocal behaviour can be explained by differences in social behaviour (e.g. group cohesion, intergroup relation, mating behaviour) and functional disparities. Possible factors responsible for the pronounced intergeneric differences in vocal behaviour between Macaca and Presbytis are discussed. PMID- 1885114 TI - Cercopithecus dryas Schwarz 1932 and C. salongo Thys van den Audenaerde 1977 are the same species with an age-related coat pattern. PMID- 1885115 TI - [Are allergies really increasing?]. AB - A presumed rise in the prevalence of atopic diseases in industrialized countries is currently subject to extensive discussion. Due to a lack of epidemiological longitudinal studies, the controversy among the experts was based mainly on speculation. Only recently have data from various European countries confirmed an increase in atopic diseases. Studies from Sweden, Switzerland and Denmark showed a definite increase in atopic diseases. Studies from Sweden, Switzerland and Denmark showed a definite increase in the prevalence of hay fever, bronchial asthma and atopic eczema, respectively. Japanese investigators have concerned themselves with the putative role of air pollutants in this development. They were able to show a relationship between exposure to particulate air pollutants (diesel exhaust) and the prevalence of mountain cedar pollinosis. To date a lack of baseline data has hampered the evaluation of epidemiologic trends in Germany. We performed a pilot survey study involving more than 1000 pre-school children that yielded initial evidence of an unexpectedly high prevalence of allergic conditions in Bavaria. A comparison with current epidemiologic data from other European countries suggests an increase in allergies in Germany similar to that observed elsewhere. PMID- 1885116 TI - [Ambulatory angiography]. AB - Outpatient angiography is justified in selected cases; patients with risk factors must be excluded. The examination should be performed as atraumatically as possible. After angiography, the patient should be kept under observation for at least 6 hours, since most complications occur during or shortly after the intervention. Only vary rarely do complications develop after the patient has been discharged, the most serious being late hemorrhage. Facilities for rapid treatment must be provided. PMID- 1885117 TI - [Lipid metabolism disorder: detection and treatment. 5: Treatment of hyperlipidemia in manifest coronary heart disease, diabetes mellitus and hypertension. National cholesterol initiative]. PMID- 1885118 TI - [The concept of amnesia and quantitative assessment of amnesic disorders]. AB - This article presents first a short historical overview of the different viewpoints concerning psychiatric approaches to define the concept "amnesia" (Ribot, Korsakow, K. Schneider, Bleuler, Bonhoeffer et al.). A generally accepted result is the differentiation between retrograde and anterograde amnesia. Research work of the last two decades has focussed on the experimental investigation of anterograde amnesia, the so-called amnesic syndrome. In this context four main factors responsible for memory performance are distinguished: encoding, retrieval, forgetting and interference. One of the main results of neuropsychological research in amnesia consists in having discovered a set of symptoms or features common to most if not all forms of amnesia. These features appear regardless of etiology and locus of lesion. This set or features is described in detail in the paper. On the basis of these amnesic features a clinical test was developed, the Berliner Amnesie Test (BAT). This standardized test can be used for the assessment from mild up to severe memory disorders. PMID- 1885119 TI - [The dynamics of emotional states in patients with epilepsy. A phenomenologic EEG analysis study]. AB - The history of the main ideas of psychogenetic epilepsy-theory is outlined. Using the antithesis of omnipotency and impotency further implications of this theoretical approach are explained. Epileptic patients suffer from a deficient structure of their self and do not overcome infantile obsolutistic thought, behavioral and emotional patterns. Their behavior and symptoms exhibit the characteristics of the "all or nothing schema". In particular conflict solving strategies of epileptics consist either in an exaggerated spirit of toleration or in violent outbursts of aggression. Destructive fits of rage, epileptic fits and psychotic derangements can be understood as manifestations of aggression on ontogenetically earlier developmental stages. From this point of view we studied the influence of the emotional states of epileptics on EEG-background activity and discharges: Conflict-centered interviews were recorded simultaneously in ten epileptic patients with EEG- and video-techniques. FFT-spectralanalysed EEG-data and discharges from visually evaluated EEG-records were correlated with hermeneutic analyses and the ratings of the emotional states. Results show significant correlations between spectral EEG-parameters and aggression, anxiety, sorrow and joy. These results were validated by further studies. Normal aggressive episodes were correlated with an increase of power in all frequency bands. Epileptic discharges occurred in over or latent aggressive impulses. In the theory of the "Kontinuitatsparadigma" a parallelism of two transitional stages is suggested: ranging from normal to pathological aggression with all its symptoms and from EEG-dynamics in normal aggression to typical discharges in epileptic aggression. The latter represents the extreme pathological end of the stage while the former is its starting-point. PMID- 1885120 TI - [Aspects of psychologic disorders in Japanese students]. AB - The present study discusses the reasons which moved 88 students during one year from April 1987 till March 1988 to make their first spontaneous visit to the Department of Psychiatry in the Health Service Center of Tokyo University. The number of patients amounted to 0.60% of the total student enrollment during the period mentioned. The sufferings which motivated their visits could be phenomenally divided into two sectors. The first sector was related to the individual problems of the students and could be sub-divided into somatic and psychic spheres. To the other sector belonged the social or intersubjective relationships with either a general or a special point of reference. The majority of cases (ca. 70% of all patients) fell into the individual sector. Some reasons for this distribution are discussed. Among the patients there was a large percentage of freshmen. This seems to be due to the internal and external milieu changes caused by entering the university life. The ICD-9 diagnosis showed that ca. 80% of the patients exhibited Neurotic disorder and Adjustment reactions. This raises the question of applicability of ICD-9 to minor ailments, frequent among the clients of a Student Health Center. The dominant source of troubles motivating students to seek psychiatric help appeared to be problems connected with the academic life, like entrance into the university, examinations, choice of field of study, and graduation. PMID- 1885121 TI - [Paroxysmal choreoathetosis]. AB - Paroxysmal Choreoathetosis (PC) is a rare disorder which is characterized by spells of involuntary movements of the limbs, the head and the trunk lasting from a minute to several hours. PC is classified in two main types. In Paroxysmal Dystonic Choreoathetosis (PDC) the attacks are prolonged and precipitated by alcohol, emotion or fatigue, in Paroxysmal Kinesigenic Choreoathetosis (PKC) the attacks last less than 5 minutes and are precipitated by sudden movements. Although the pathophysiology of the disorder ist still uncertain, it is supposed to be an extrapyramidal disorder. Clinical features, therapeutical and differential diagnostic aspects are discussed. There is a certain risk that the disorder is misinterpreted as psychogenic or hysterical in nature. The mostly good response to medication can help the patients avoid superimposed emotional problems. PMID- 1885123 TI - [Recent study on etiology and therapy of Basedow's disease]. PMID- 1885122 TI - [Pathophysiologic regulatory mechanisms in chronic schizophrenia]. AB - Two collectives of chronic schizophrenics were psychometrically rated by means of the BPRS and of Gebhardt's primary AMP-scales. Their scores of coexistent Positive and Negative Symptomatology were correlated with equivalents of catecholergic levels of tone as represented by plasma tyrosine concentration in its role as the catecholergic precursor. Levels of catecholergic tone state- and time-dependently correlated directly with Positive and inversely with Negative Symptomatology. Opposite ends of catecholergic tone from supra- to subnormal ranges ran parallel to a psychometric continuum from predominant Positive to predominant Negative Symptomatology, to a diagnostic continuum from "paranoid" to "disorganised/hebephrenic", and to a global metabolic continuum from under- to overweight. Findings did not support the hypothesis on psychotogenic dopaminergic supersensitivity. Postulated was a primary psychotogenic process of denervation or/and degeneration of a specific 'trigger system', and supersensitivity-induced neuronal damage was conjectured the biological substrate of Negative Symptomatology. A pathophysiological hypothesis put forth, corresponded with Cannon's Rules within the frame of functional neuronal plasticity. PMID- 1885124 TI - [A comparative electron microscope study on the fine structure of the muscular coat in the common bile duct]. AB - Little is known about the architecture of common bile duct, especially smooth muscle, except for Oddi's sphincter. The purpose of this study is to reveal the ultrastructural architecture of the upper part of the common bile duct from the viewpoint of comparative anatomy. Animals used in this study were the hamster, rat, dog, monkey and rabbit, and the results obtained were as follows. There were considerable differences in the structural appearance and distribution of smooth muscle cells in the upper part of the common bile duct among the animals examined. In the rat, a small number of smooth muscle cells were sparsely distributed in the subepithelial connective tissue of the duct. In the dog, smooth muscle cells showed a star-shaped appearance with many cytoplasmic processes, by which networks were formed. In the monkey, smooth muscle cells with fibroblast-like appearance were circularly distributed. In the monkey and rabbit, muscular coats consisting of typical smooth muscle cells were observed in the outermost layer of the duct. The muscular coat in the monkey was arranged longitudinally, and in the rabbit circularly. The muscular coat in the rabbit was thicker than that in the monkey. In the hamster, however, the duct wall was devoid of smooth muscle cells. The present study suggests that the occurrence of smooth muscular coat is not essential for transport of the bile. PMID- 1885125 TI - [Prognostic factors for predicting the outcome of pulmonary sarcoidosis: clinical study based on cross-sectional survey of 115 cases]. AB - We studied cross-sectionally 115 patients (36 men & 79 women) to analyze the prognostic factors retrospectively. These patients were examined for a response to our request to visit our institution, out of 277 patients (114 men & 163 women) with pulmonary sarcoidosis in our institute for the period from 1956 to 1988. The outcome of sarcoidosis is evaluated by chest X-rays (CXR) and other laboratory test regarding pulmonary, cardiac, ocular or other organ. The mean follow-up interval was 78.2 months (range 1-271 months) and the mean age was 42.5 years at the initial examination (range 5-71 years). Among those patients, 101 patients were followed-up over one year period. Selection bias was noted by the predominance of women and ocular involvement (70% and 60% in 101 patients, 59% and 50% in 277 patients). CXR prognosis and systemic prognosis were related to age at the final examination and observation time. These results indicate that abnormal CXR findings and systemic functional deficit resided in the elderly and disease itself tended to regress beyond 2 years' observation. Both chronic tonsillitis and ocular involvement were significantly correlated with CXR prognosis and systemic prognosis, by Mantel-Haenzel's chi 2-test corrected by both of age and observation time. The relative risk was not enhanced in the presence of both ocular involvement and chronic tonsillitis. These clinical study results suggest that both of ocular involvement and chronic tonsillitis are important prognostic factors for predicting the outcome in the natural history of sarcoidosis. PMID- 1885126 TI - A case of transient elevation of the serum carcinoembryonic antigen and associated with severe malnutrition and low T3, T4 syndrome. AB - A patient with a transient elevation of the serum carcinoembryonic antigen (CEA) associated with a benign disease was reported. The elevation of CEA was noted in the patient with low T3, T4 syndrome associated with malnutrition due to malabsorption syndrome induced by post-gastrectomy and chronic pancreatitis. Mild liver dysfunction and diabetes mellitus were also noted. The CEA level decreased as T3, T4 level and malnutrition were improved by administration of a massive digestive enzyme preparation. This inverse correlation between the serum CEA and serum T3, T4 levels suggested that high levels of the serum CEA can be found in the patient with malnutrition. PMID- 1885127 TI - [Severe alcoholic cirrhosis associated with spur cell anemia and DIC]. AB - A 29-year-old male who had a 15-year history of alcohol drinking was admitted with a 5-month history of jaundice in July 1989. Laboratory examinations revealed that he had hemolytic anemia and severe liver damage. Erythrocytes of peripheral blood showed typical spiculated cells on light microscopic and scanning electron microscopic studies. Free-cholesterol/phospholipid ratio of the erythrocyte membrane was elevated, and the level of chenodeoxycholic acid increased in serum. The patient was diagnosed as having advanced alcoholic cirrhosis associated with spur cell anemia. Two months after admission, he was complicated with chronic disseminated intravascular coagulopathy (DIC). Anemia, hepatic failure and DIC progressed, and the patient died six months after admission. The mechanism of the formation of spur cells was discussed. PMID- 1885128 TI - The health insurance picture in 1990. PMID- 1885129 TI - A new look at rising mental health insurance costs. PMID- 1885130 TI - Medicare payment to psychiatric facilities: unfair and inefficient? PMID- 1885131 TI - Disclosure of outpatient prescription drug benefits in HMOs. PMID- 1885132 TI - Problems in gaining access to hospital information. PMID- 1885133 TI - A closer look at health care in Canada. PMID- 1885134 TI - Interpreting public opinion surveys. PMID- 1885135 TI - Basing policy on survey data: proceed with caution. PMID- 1885136 TI - III. Grants. AIDS. PMID- 1885137 TI - Financing policy for mental health services. PMID- 1885138 TI - The rising costs in health system reform. PMID- 1885139 TI - Quality measures: key to health care reform. PMID- 1885140 TI - Informing the public to achieve health reform. PMID- 1885141 TI - Market reform in the community. PMID- 1885142 TI - Translating opinion into action. PMID- 1885144 TI - Options for universal coverage. PMID- 1885143 TI - Debating national health insurance alternatives. PMID- 1885145 TI - Issues in prescription drugs and the elderly. PMID- 1885146 TI - Contributions from America's philanthropic foundations. PMID- 1885147 TI - Practice guidelines and cholesterol policy. PMID- 1885148 TI - Rationing care in Oregon: the new accountability. PMID- 1885149 TI - Ethics and priority setting in Oregon. PMID- 1885150 TI - Health care rationing: a critical evaluation. PMID- 1885152 TI - [The future--view of health science]. PMID- 1885151 TI - Breaking American health policy gridlock. PMID- 1885153 TI - [Analysis of leukocyte adhesion deficiency]. PMID- 1885154 TI - [Evaluation of the factors increasing medical expenses of the National Health Insurance]. PMID- 1885155 TI - The cycle of the seminiferous epithelium and stages in spermatogenesis in dd mice. AB - For the basis to study the testicular functions using dd-mice, the cycle of the seminiferous epithelium and stages in spermatogenesis, classification of late spermatogenesis, and postnatal development of spermatogenesis were examined by light and electron microscopy in the testes from these animals at day of birth and 1, 2, 3, 4, 5, and 8 weeks of age. For light microscopy, paraffin sections of the testes were stained with periodic-acid and Schiff reagent (PAS) and hematoxylin. In spermiogenesis, 16 steps of spermatids were distinguished according to shapes of the nuclei and acrosomes. Step 15 and 16 spermatids, which have similar nuclei and acrosomes, were easily distinguishable by positions of nuclei and appearance of basophilic granules in the cytoplasm; steps 15 and 16 were thus subdivided into 3 and 2, respectively. The granules were accumulations of ribosome-like particles. Step 13 spermatids were present with step 1 spermatids, step 14 with steps 2 and 3, step 15 with steps 4-6, and step 16 with steps 7 and 8. Thus, the cycle of the seminiferous epithelium was divided into 12 stages (stages I-XII) in the order of steps 1 to 12. Type A spermatogonia were present in all stages, and intermediate and type B spermatogonia appeared from stages II and VI, respectively. In primary spermatocytes, the resting phase appeared from stage VII, leptotene from stage VIII, zygotene from stage X, pachytene from stage III, diplotene in stage XI, and diakinesis and secondary spermatocytes in stage XII. The seminiferous tubules were lined by Sertoli cells and contained gonocytes at day of birth, type A spermatogonia appeared at 1 week of age, spermatogenesis proceeded until pachytene spermatocytes at 2 weeks, until step 1 spermatids at 3 weeks, and all stages of the seminiferous epithelium were completed at 5 weeks. The findings indicate that combination of germ cells in each stage of the seminiferous epithelium in dd-mice does not correspond to generally accepted one, step 15 and 16 spermatids are accurately classified by referring the position of nuclei and appearance of granules in the cytoplasm, and spermatogenesis in immature mice proceeds faster than in adults. PMID- 1885156 TI - [Mouse monoclonal antibody (FKH1) detecting human melanoma-associated antigens: production, partial characterization and immunohistochemical analysis]. AB - A mouse monoclonal antibody, FKH1, was produced to detect cytoplasmic melanoma associated antigen. FKH1 was raised using cultured human melanoma cell line KHm-6 as immunogen. Reactivity of this antibody was assessed by immunohistochemical techniques. Positive reactions were seen against 5 human melanoma cell lines and cultured human epidermal melanocyte. It stained cytoplasm of melanoma cells in a diffuse and granular pattern with indirect immunofluorescence. Immunoelectron microscopy showed diffuse distribution of immuno-reactant in the cytoplasm of KHm 1 cells excluding melanosomes and other subcellular organelles. In immunoblotting, FKH1 bound with proteins having molecular weight of 71 kd and 55 kd extracted from KHm-6 cells. Reactivity against frozen and alcohol-fixed paraffin-embedded melanocytic tumors was also tested with indirect immunofluorescence or ABC (avidin biotin peroxidase complex) techniques. All cases of frozen sections from benign and malignant melanocytic tumors including 2 cases of amelanotic melanoma showed positive staining with FKH1. In fixed tissues, reactivity was 16/19 (84.2%) in malignant melanoma and 30/44 (68.2%) in other melanocytic tumors. FKH1 did not react against normal melanocytes, C-type nevus cell, intradermal nevus pigmentosus with neuroid structure and neurofibroma. It was demonstrated that FKH1 recognized proliferative melanocytes originated from melanoblast or melanoblastic nevoblast. FKH1 failed to stain normal human peripheral nerves and nonmelanocytic tumors except APUDoma and malignant Merkel cell tumor. In halo nevus, nevus cells were clearly distinguished from intermingling inflammatory cell infiltrate. It was suggested that FKH1 is a useful monoclonal antibody in diagnosing human malignant melanoma, particularly in evaluating tumor thickness of Breslow more precisely. PMID- 1885157 TI - [A study of forearm muscle metabolism in patients with chronic heart disease]. AB - To assess forearm exercise capacity and exercise energy metabolism in relationship to forearm muscle mass and blood flow in patients with chronic heart disease, 22 patients (NYHA class I (C1) 8, class II(C2) 10, class III (C3) 4) and 10 normal subjects were studied using Phosphorus-31 magnetic resonance spectroscopy (31P-MRS). First, the maximal cross sectional area (MCA) of the forearm flexor muscles was estimated in each individual using magnetic resonance imaging. Then, during multistage forearm flexor exercise, 31P-MRS was performed to estimate phosphocreatine (PCr), inorganic P (Pi), and intracellular pH. Forearm blood flow was measured by plethysmography. An initial work load of forearm exercise was decided by MCA as 1 J/cm2, and multistage exercise was done with an increment of 1 J/min/cm2 to the point of maximal muscle exhaustion. The maximal load (J/min) was decreased in cardiac groups as NYHA class advanced. However, the difference among all groups except group C3 was not significant when the max load was adjusted for muscle MCA. As the work load was increased during forearm exercise, PCr and intracellular pH decreased, and Pi increased in every group. Standardized PCr [PCr/(PCr + Pi)] was lower in group C2 and C3 than in group N at each work load. At high work loads, intracellular pH tended to be lower in group C2 and C3 than in group N and C1. Forearm blood flow during forearm exercise was not different among the four groups. In the maximal exercise test using upright ergometer, peak oxygen uptake and anaerobic threshold were lower in group C1, C2 and C3 than in group N.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1885158 TI - Modulation of the receptive field center response of cat retinal ganglion cells by the shift response signal through amacrine cells. AB - The effect of a stationary and an oscillating grating situated greater than 30 degrees from the RFC on the receptive field center response was examined. The transient firing rate of the center response was suppressed by the oscillating grating for all types of cells. The stationary grating also suppressed the transient firing but the degree of suppression was significantly less than that with the oscillating grating. There was also a significant elevation of the sustained firing rate in Y-cells. The on-going discharges were elevated in all types of units except on-center X-cells when the grating was oscillated. An increase in the area of a grating annulus did not increase the degree of suppression of the center response. This lack of spatial summation of the shift response was related to the properties of the on-off transient amacrine cells. PMID- 1885159 TI - [A morphological study on the brain in wriggle mouse Sagami, a new neurological mutant with dystonic disorders, with special reference to the abnormality of the cerebellum]. AB - The 'Wriggle Mouse Sagami (WMS)' is a new neurological mutation that was discovered in an inbred strain of BALB/c mice at the Ohmura Institute for Laboratory Animals (Address: Zama 228, Kanagawa, Japan) in 1984. The affected characteristics are transmitted by an autosomal recessive gene (wri). The clinical symptoms are characterized by dystonic involuntary movements, such as fine tremors of the forelimbs, hypertonic musculature of the extremities, difficulty in maintaining an upright posture, writhing of the trunk, wriggling of the neck up-and-down and from side to side without any coordination between the movements of the limbs and trunk, and inability to walk a staigho that begin at 10 days to 2 weeks after birth and are progressive until 12 weeks of age. Here a morphological study on the brain of the WMS with special reference to the cerebellum was intended. The results were as follows: (1) In spite of these severe clinical symptoms, no marked abnormalities were observed in the cyto- and myeloarchitecture of the central nervous system, although the size of the whole brain was somewhat reduced and the molecular layer of the cerebellum was relatively hypotrophic compared with the granule cell layer. (2) The motor tracts investigated were normally detected by the retrograde HRP-labeling method. (3) Slight abnormality of the dendritic trees and spines, and remarkable axonal swellings of the Purkinje cells were demonstrated by a sensitive immunohistochemical method for inositol 1,4,5-trisphophate receptor protein (P400 protein). These changes were also evaluated by the Golgi method. (4) In electron microscopy of the molecular layer of the WMS cerebellum, parallel fibers seemed to be reduced and shrunken, and their synaptic contacts on the dendritic spines of the Purkinje cells were clearly reduced even at 17 days after birth. (5) Consequently, the Purkinje cells were possibly affected by failure of accurate connection with input fibers or by synaptic dysfunction, which might occur over the entire central nervous system. PMID- 1885160 TI - [Abnormalities in mitochondrial creatine kinase activity in cardiomyopathic hamsters]. AB - The creatine kinase system is related to intracellular high-energy phosphate transfer. Mitochondrial creatine kinase catalyzes the transfer of high-energy phosphate between creatine and ATP generated in mitochondria. Creatine phosphate generated in this process is transferred to myofibril. Mitochondrial creatine kinase abnormalities cause the decrease of ATP level in cytoplasm through the disorder of ATP transfer. If such decrease happens in myocardium the depressed cardiac function is suspected. I studied the time course of alterations of the creatine kinase system in BIO14.6 (the model of hypertrophic cardiomyopathy) at 5 weeks, 20 weeks, 50 weeks, and 62 weeks of age, and in BIO53.58 (the model of dilated cardiomyopathy) at 5 weeks and 20 weeks of age. In BIO14.6, creatine kinase activity of myocardium and isolated mitochondria was decreased in 20, 50, 62-week-old hamsters. The share of mitochondrial creatine kinase in the total tissue enzyme activity was decreased, and the share of BB form was increased in 50, 62-week-old hamsters. In BIO53.58, creatine kinase activity of myocardium and isolated mitochondria was decreased in 20-week-old hamsters. The share of mitochondrial creatine kinase was increased, and BB form was decreased in 5, 20 week-old hamsters. The experiments suggest alterations in the creatine kinase system occur at 20 weeks of age in BIO14.6 and at neonatal phase in BIO53.58. These alterations of creatine kinase system may contribute to depressed cardiac function in cardiomyopathy. PMID- 1885161 TI - [Immunohistochemical study of the extracellular matrix in non-small cell lung cancer: relation to lymph node metastasis and prognosis]. AB - The distribution of type IV collagen and laminin in the basement membrane (BM), and fibronectin in the peritumoral stroma of 112 lung cancers (62 adenocarcinomas, 50 squamous cell carcinomas) was studied using immunohistochemical techniques to compare with tumor size, lymph node metastasis and prognosis. In normal lung tissues, type IV collagen and laminin stainings were continuously linear in bronchial BM, blood vessel BM, around bronchial gland and along alveolar septa. Immunoreactivity of fibronectin was shown in BM and stroma. In lung cancers, type IV collagen and laminin stainings were observed in continuous or discontinuous pattern around carcinoma cells, and partially unrecognizable. Staining patterns were divided into continuous (C) and discontinuous (D). And fibronectin patterns were divided into weakly and strongly positive. In relation between staining pattern and lymph node metastasis, in adenocarcinomas, C pattern of type IV collagen staining without lymph node metastasis occurred in 73.9% and with metastasis in 26.1%, on the other hand, D pattern without lymph node metastasis occurred in 25.6% and with metastasis in 74.4%. The correlation was statistically significant (p less than 0.01). And also, in squamous cell carcinomas, C pattern without lymph node metastasis seen in 71.4% and with metastasis in 28.6%, on the other hand, D pattern without lymph node metastasis seen in 27.6% and with metastasis in 72.4%. The correlation was statistically significant (p less than 0.01). But staining pattern of fibronectin didn't correlate to lymph node metastasis. In comparison between C and D patterns, C pattern was associated with longer survival than D pattern (p less than 0.01). In lung cancers without lymph node metastasis, C pattern tended to be higher in 5-year-survival than D pattern, but not significant. These findings suggest that staining pattern of type IV collagen and laminin might be correlated to cancer metastasis and useful to estimate the prognosis. PMID- 1885162 TI - Heterogeneity of monoclonal antibody distribution and radiation dose in tumors: a modeling analysis. AB - For successful use of monoclonal antibodies and their conjugates for diagnosis and therapy, it is helpful to understand both macroscopic and microscopic aspects of antibody distribution. Antibody distribution in a tumor is simulated by splicing together information on global pharmacokinetics, transport across the capillary wall, diffusive penetration through the tumor interstitial space, and antigen-antibody interaction. One interesting implication of this simulation is a microscopic dosimetry for radioimmunotherapy. The information of microscopic radioconjugate distribution will enable us to calculate absorbed dose in a tumor at the microscopic scale. The first step is to simulate the spatial antibody concentration profile in a tumor as a function of time after intravenous (bolus) injection, using reasonable values for the parameters involved. The second step is to calculate, also as a function of time, the absorbed radiation dose distribution resulting from each concentration profile. Parameter values for IgG pharmacology and a radiation point source function for I-131 are used to explore the effect of affinity on the antibody distribution and consequent absorbed dose in the tumor. The geometry simulated corresponds to a spherical nodule of densely packed tumor cells. Absorbed doses are calculated for radiation from a single nodule and for a cubic lattice of such nodules. This modeling analysis demonstrates that 1) antigen-antibody binding in tumors can retard antibody percolation; 2) high antibody affinity at a given dose tends to decrease antibody percolation and result in a heterogeneous distribution; 3) heterogeneous antibody distribution results in heterogeneous absorbed dose. This is more apparent in the case of radiation from a single nodule or small tumors. PERC and PERC-RAD, the computer program packages developed for these analyses, provide a convenient and flexible way to assess the impact of macroscopic and microscopic parameters on the distribution of immunoconjugates (PERC) and the consequent absorbed radiation dose in tumors (PERC-RAD). This mathematical model and the general principles developed here can be applied as well as to other biological ligands and beta emitters. PMID- 1885163 TI - [The in vivo measurement of ischemic myocardial interstitial metabolites in the beating canine heart: measurement of adenosine using an improved microdialysis technique]. AB - The purpose of this study was 1) to evaluate the usefulness of myocardial microdialysis method in the beating canine heart for the measurements of myocardial interstitial adenosine, inosine and hypoxanthine concentrations and 2) to determine their changes during myocardial ischemia. Microdialysis probes modified for the beating myocardium were implanted in the left ventricular myocardium of pentobarbital-anesthetized dogs. The implanted microdialysis probes were perfused with saline solution containing low molecular heparin in order to prevent thrombotic obstruction of the dialysis membrane. The concentrations of adenosine and its metabolites, inosine and hypoxanthine, in the effluent dialysate were determined using high-performance liquid chromatography (HPLC). Dialysate concentrations of adenosine and its metabolites were considerably high immediately after the insertion of microdialysis probes. However, the concentrations gradually declined and stabilized by 150 min. Occlusion of the left anterior descending artery for 30 min caused a marked increase in dialysate adenosine and inosine levels, and a small increase in hypoxanthine level in the ischemic myocardium. These results suggest that the myocardial microdialysis method is very useful for the in vivo monitoring of interstitial levels of adenosine and its metabolites in the beating canine heart. PMID- 1885164 TI - [Genetic riddle hidden in the lower abdominal tumor]. PMID- 1885165 TI - The temporal bone: an organ in search of a histopathology. AB - The pathology of the temporal bone and the inner ear in particular has been a neglected area for histopathologist. This review sets out to answer a number of questions on the topic: why is it neglected; how do you learn its anatomy; how do you process it; why do it; and who should do it? The histopathological features of cholesteatoma, otosclerosis and presbyacusis are discussed in detail and future areas of research are identified. PMID- 1885166 TI - Monocytoid B-cell lymphoma: morphological variants and relationship to low-grade B-cell lymphoma of the mucosa-associated lymphoid tissue. AB - Twenty-eight cases of monocytoid B-cell lymphoma of lymph nodes and 16 lymph node metastases of primary gastric lymphomas, mostly low-grade B-cell lymphomas of mucosa-associated lymphoid tissue (MALT) type were investigated morphologically and immunohistochemically. Both groups showed the same morphological and immunohistochemical features: diagnostically important sites of infiltration were the sinuses and the marginal zones. The tumour cells were either medium-sized or small. The cytoplasm stained grey with Giemsa and was sometimes rather pale. In imprints the grey colour of the cytoplasm was a characteristic feature. The medium-sized cell type was more frequent; in one third of the cases it was combined with a prominent lymphoplasmacytic component from the same clone, and it resembled the monocytoid B-cells of the sinuses. The small cell type was less common, was not combined with a lymphoplasmacytic component and more closely resembled marginal zone cells. The difference was underlined by the negative reaction with the monoclonal antibody Ki-B3 in the small cell type, which, conversely, was positive in the medium-sized cell type and in the monocytoid B cell reaction of the sinuses. Both of these cell types, however, showed a granular reaction with the new monoclonal antibody Ki-Mlp. The morphological and immunohistochemical parallels are arguments in favour of the assumption that monocytoid B-cell lymphoma is the nodal equivalent of low-grade B-cell lymphoma of MALT type. This is further supported by the fact that in nine of our 28 cases of monocytoid B-cell lymphoma, lymphomas were found simultaneously or subsequently in organs of the MALT. Monocytoid B-cell lymphoma must be differentiated from an infiltration that occurs in the form of clusters of monocytoid B-cells in other low-grade B-cell lymphomas, especially in immunocytoma with a high content of epithelioid cells. PMID- 1885167 TI - Diffuse sclerosing papillary carcinoma of the thyroid gland: immunohistochemical analysis of the local host immune response. AB - Surgical specimens from four patients with diffuse sclerosing papillary carcinoma of thyroid were examined by electronmicroscopy. In addition, immunohistochemical examination using a panel of monoclonal and polyclonal antibodies was carried out in order to investigate the expression of HLA-DR antigen, the presence of Langerhans' cells and the phenotypic characteristics of the inflammatory infiltrate. The ultrastructural study showed that the intraglandular dissemination, typical of this tumour, was due to massive lymphatic invasion. Many Langerhans' cells were observed among tumour cells and in the lymphoid infiltrates in proximity to tumour foci. HLA-DR expression was seen on macrophages, Langerhans' cells, endothelial cells, lymphoid cells, many tumour cells and in some non-neoplastic follicles close to tumour clusters and lymphoid infiltrates. The immunohistochemical analysis of the inflammatory infiltrates showed a high proportion of B- and T-cells, and moderate numbers of plasma cells. Our results suggest that the tumour-specific immune response can give rise to an autoimmune reaction involving non-neoplastic follicles. It is suggested that this could be one of the mechanisms responsible for immunofacilitation of tumour growth. PMID- 1885168 TI - Failure of elastin development in hypoplastic lungs associated with oligohydramnios: an electronmicroscopic study. AB - Pulmonary hypoplasia associated with oligohydramnios results in delayed maturation of fetal lung as assessed at light microscope level. Using an elastin specific electron-microscopic staining technique, we report absent elastic tissue development in the septal crests of these lungs even at term. PMID- 1885169 TI - Diltiazem-induced granulomatous hepatitis. PMID- 1885170 TI - Non-systemic diffuse lymphangiomatosis of spleen and liver. AB - We present a 27-year-old woman with non-systemic diffuse lymphangiomatosis of spleen and liver. The tumour consisted of capillary and cavernous lymphatic vessels located in abundant fibrous tissue. The vascular endothelium showed immunoreactivity for factor VIII-related antigen. A basal lamina could be demonstrated immunohistochemically and by electronmicroscopy. PMID- 1885171 TI - Malignant peritoneal mesothelioma giving rise to multiple intestinal polyps. PMID- 1885172 TI - Classification of primary intracranial sarcomas and other central nervous system neoplasms. PMID- 1885173 TI - Adding quality to the health care cost equation. PMID- 1885174 TI - Diagnostic criteria for obsessive-compulsive disorder. PMID- 1885175 TI - For whom the statute tolls: extending the time during which patients can sue. PMID- 1885176 TI - Combining modalities to treat a young woman with a history of bingeing and purging. PMID- 1885177 TI - Mental health services under a U.S. national health insurance plan. AB - Sometime during the 1990s, the U.S. Congress could enact legislation that would establish universal access to basic hospital and physician services and, later, create a national health insurance plan. The author explores the potential effect of these programs on state psychiatric facilities; short-term acute psychiatric care facilities, including those under for-profit ownership; mental health professionals; and delivery of patient care. Each year about 63 million uninsured Americans would be eligible for basic health care under a universal access program, and mentally ill patients who are now unable to afford care would then be eligible for limited mental health services. National health insurance, enacted after the universal-access approach fails, is likely to support the current trend of proportionately more ambulatory and less inpatient mental health care. Wealthy Americans are likely to use the national health insurance system but may also use private mental health services, thereby perpetuating the current pluralistic health care delivery system. PMID- 1885178 TI - Men's changing social roles in the 1990s: emerging issues in the psychiatric treatment of men. AB - In the last two decades, men's social roles have changed to incorporate the increasing time they spend with their families, their greater concern about adult children's leaving or returning home, and alternative sexual preferences and life styles. One related development is the increased amounts of psychiatric distress reported by men in recent years. Mental health professionals should be familiar with these and other complex issues specific to men and with how such issues might manifest themselves in psychotherapy. PMID- 1885179 TI - Architectural guidelines for state psychiatric hospitals. AB - Mental patients are a population who have special needs for which architectural interventions can be helpful. The physical settings in state hospitals often do not provide the proper environment for therapeutic progress, nor do they contribute to the implementation of new programs for care. The author presents seven guidelines related to specific elements of the physical setting, such as space differentiation, color, texture, and lighting, that administrators and staff can use in analyzing existing hospital settings and in discussing designs for renovations or new construction with architects. The application of such guidelines should help establish architecture as a valuable tool in the therapeutic process. PMID- 1885180 TI - A ten-year perspective of mortality risk among mentally ill patients in sheltered care. AB - The ten-year risk of mortality was assessed for a sample of 393 former psychiatric patients who were living in sheltered care settings in California in 1973. Compared with the general state population, residents of sheltered care facilities were 2.85 times more likely to die than would be expected if age specific rates for the state applied to them. Excess mortality was due to heart disease, cerebrovascular diseases, and all other natural and unnatural causes except malignant neoplasms. The mortality rate of the subjects was closer to that of a low-income subsample of the California population, suggesting that the high mortality rates of patients in sheltered care settings may be due to their low income status. PMID- 1885181 TI - A retrospective cohort study of falls in a psychiatric inpatient setting. AB - Several factors increase the psychiatric inpatient's risk of falling, including side effects of medications and mental disorders that decrease awareness of environmental hazards. In this study, rates of falling were determined for a cohort of 4,156 psychiatric inpatients over 34 months. A total of 494 falls occurred among 376 patients. Thirty-five percent of the patients who fell required medical or nursing intervention. Forty-eight percent of the falls occurred in the over-60 age group. When other results were adjusted for age, neither gender nor diagnosis was found to increase the risk of falling, except for depressed patients under 20 years old, who were at less risk, and psychotic patients in their 60s, who were at greater risk. The authors discuss the costs of falls and preventive efforts instituted in their setting. PMID- 1885182 TI - Correlates of problem drinking among homeless men. AB - Multiple regression analysis was used to identify correlates of problem drinking among 165 homeless men in St. Louis, Missouri. Variables that were the strongest predictors of alcoholism included number of stressful events before becoming homeless, age, current life satisfaction, psychopathology, and prior mental hospitalization. The full-scale model predicting problem drinking produced a total explained variance (R2) of .38. In contrast with findings from previous research on the homeless, the length of time homeless and the degree of transience were not predictive of alcoholism. Similarly, social support had no impact on problem drinking. PMID- 1885183 TI - A model for predicting discharge against medical advice from adolescent residential treatment. AB - Characteristics of adolescents discharged from a psychiatric residential treatment center were examined to create a model for predicting patient discharge against medical advice (AMA). Subjects were 81 adolescents in two consecutive cohorts discharged between 1983 and mid-1988 (N = 49 and N = 32). In both groups 41 percent of the discharges were AMA. Logistic regression analysis found that an equation based on three factors--history of juvenile court involvement, unsupportive family attitude toward treatment, and diagnosis of conduct disorder- was 69 percent accurate in predicting discharge status in group 1 and 81 percent accurate in predicting discharge status in group 2. A positive correlation between rates of staff turnover and AMA discharge was noted. PMID- 1885184 TI - Arrest and incarceration of civil commitment candidates. AB - To gauge whether more stringent civil commitment criteria have led to the criminalization of mentally ill persons, forcing them into jails and prisons instead of treating them, a statewide sample of 1,226 civil commitment candidates in North Carolina was tracked for six months after their commitment hearings. Only 72 sample members were arrested during the period, mostly for burglary or larceny (22 arrests), simple or aggravated assault (17 arrests), and minor offenses (40 arrests), including drunkenness, trespassing, and traffic violations. Fourteen sample members were jailed, and two were sent to prison. The mentally ill who were not involuntarily hospitalized or who were hospitalized for only short periods were seldom arrested; when they were arrested, the charges were generally for nondangerous offenses. PMID- 1885185 TI - Moonlighting: why training programs should monitor residents' activities. AB - Moonlighting by psychiatric residents, or employment outside the residency program, is a longstanding and widespread practice. The author contends that moonlighting detracts from residents' ability to gain full benefit from their educational program, compromises the safety of patients treated by residents who moonlight in unsupervised settings, and exposes health care institutions to risk of costly legal actions. Although moonlighting should ideally be eliminated, a workable alternative to the current system would include oversight by residency program directors of residents' extracurricular employment to assure that the assignments complement the educational program. Institutions that employ moonlighting residents would also reimburse the residency program for selecting appropriate residents to fill the positions they offer. PMID- 1885186 TI - Moonlighting: what residents do in their free time is their decision. AB - Available data do not support the claim that moonlighting, or employment outside psychiatric residency programs, is a dangerous activity for residents, patients, or employers of moonlighters. Moonlighting may beneficially supplement the education of a psychiatric resident as well as be important to residents economically. The author contends that the role of psychiatric educators is to assure the competence of graduates of psychiatric residency programs to practice psychiatry. How residents use their free time is their own concern, not the concern of psychiatric educators, as long as residents fulfill their educational and training responsibilities. PMID- 1885187 TI - Characteristics of long-stay patients on the psychiatric service of a university hospital. PMID- 1885189 TI - Improving case assignments and caseload management at a community health center. PMID- 1885188 TI - Characteristics of patients who are resistant to deinstitutionalization. PMID- 1885190 TI - Reduced frequency of aggressive behavior in forensic patients in a social learning program. PMID- 1885191 TI - Quality of life of seriously mentally ill persons in Mississippi. PMID- 1885192 TI - Dissociative disorders. PMID- 1885193 TI - Schizoaffective disorders. PMID- 1885194 TI - Legalization of drugs. PMID- 1885195 TI - Drug-prescribing guidelines. PMID- 1885196 TI - The Maryland Plan. PMID- 1885197 TI - Data watch. Arthritis becoming more prevalent in U.S. PMID- 1885198 TI - Hospitals face tough issues in years following mergers. AB - Despite fears in recent years that the federal government and courts would make hospital mergers impossible, mergers are continuing to take place at a regular pace. But what happens in the aftermath of a hospital merger--both to the hospitals involved and to their communities? Four case studies explore the difficult issues that hospitals face. In addition, we take a look at the Roanoke and Rockford cases, and what the hospitals involved are doing today. PMID- 1885199 TI - Objective measures prove value of risk management. AB - Risk managers now have data to prove the value of what they do: A new study shows that certain risk-management activities are associated with a lower number of claims against hospitals. And this year, risk managers' agendas are more crowded than ever before. They must comply with a host of new regulations mandated by the Patient Self-Determination Act, the Americans with Disabilities Act, and the Safe Medical Devices Act. PMID- 1885200 TI - Physician execs bring clinical insight to non-clinical challenges. AB - Many physicians look to administrative careers as a natural step in their professional development. But the training and development of a hospital manager is strikingly different from that of a clinician. Physician executives who've made the transition to a variety of posts, including that of CEO, speak out on the shifts and surprises involved in making the transition. PMID- 1885201 TI - Questions about geographic reclassification spur debate. AB - The recent uproar over problems with Medicare's hospital geographic reclassification process has produced few long-term solutions so far. Experts say the large number of hospitals being reclassified indicates that the current methods are inadequate. They hope the current debate eventually will lead to a broader solution. The recent problems "certainly seem to have strengthened the resolve to see if there is an answer everyone can agree on," says one observer. PMID- 1885202 TI - Retreats advance the corporate culture. PMID- 1885203 TI - Court ruling draws new attention to practice doctrine. PMID- 1885204 TI - CEOs face mounting stress from finances, regs. PMID- 1885205 TI - Inhibition of polymorphonuclear leukocyte-mediated endothelial cell detachment by antileukoprotease: a comparison with other proteinase inhibitors. AB - The role of elastase and proteinase inhibitors in polymorphonuclear leukocyte(PMN)-mediated injury to human umbilical cord venous endothelial cells (HUVEC) was investigated. Both purified human neutrophil elastase and PMN that were stimulated with serum-treated zymosan (STZ) induced detachment, but not lysis of HUVEC. PMN-, but not purified elastase-mediated detachment was enhanced by the presence of methionine, which indicates a role for reactive oxygen metabolites in PMN-mediated HUVEC detachment. Detachment of HUVEC could be inhibited by secretory leukocyte proteinase inhibitor or antileukoprotease (ALP), alpha 1-proteinase inhibitor (alpha 1-PI) and N-methoxy-succinyl-ala-ala-pro-val chloromethyl ketone (CMK). At concentrations at which elastase-mediated detachment was maximally inhibited, ALP and CMK, but not alpha 1-PI, were also able to inhibit maximally PMN-mediated detachment. An explanation for this difference could be that the larger size of alpha 1-PI reduces the access of alpha 1-PI to the interface between the PMN and the HUVEC. PMID- 1885206 TI - Cytotoxic activity of lymphocytes infiltrating progressive and regressive tumor variants from a rat colonic cancer. AB - Two tumor cell variants (PROb and REGb) isolated from a single chemically-induced rat colon adenocarcinoma were previously shown to differ in their tumorigenicity. When injected into syngeneic BDIX rats, PROb cells induce progressive tumors whereas REGb cells give rise to tumors which always regress. PROb and REGb variants also differ in their capacity to induce an immune response in the syngeneic host. Regression of REGb tumors could have been mediated by cytotoxic effector cells acting at the tumor site. To test this hypothesis, the cytolytic activity of non-adherent lymphoid cells isolated from PROb and REGb tumors and from the spleen of the same animals were compared. The same number of infiltrating lymphocytes was recovered per gram of PROb or REGb tumor. The cytolytic activity of tumor infiltrating lymphocytes, as that of spleen lymphocytes, was predominantly non specific, as demonstrated by their ability to kill YAC-1 cells, an NK-sensitive cell line. PROb cells were relatively resistant to the cytotoxic activity of spleen or tumor infiltrating lymphocytes. In the regressing REGb tumors, the cytotoxic activity of tumor infiltrating lymphocytes to homologous cells or to YAC-1 cells was low and significantly inferior to that of the corresponding spleen lymphocytes. These results suggest that the cytotoxic activity of lymphocytes was impaired at the local, intratumoral level, even in spontaneously regressing tumors. PMID- 1885207 TI - Reduced expression of HLA-DP antigens on PWM stimulated T lymphocytes in patients suffering from psoriasis vulgaris. AB - 24 psoriasis vulgaris patients were investigated for the expression of class II HLA antigens on the surface of PWM-stimulated T lymphocytes. The percentage of the expression of HLA-DP antigens ranged from 50.1% to 82.6% compared to a 100% level in healthy controls (p less than 0.005). No significant differences in the expression of HLA-DR antigens were observed. A higher frequency of some HLA antigens was found in the group of patients studied: B13 - 23.1%/6.2%, B 17 - 15.4%/7.1%, and Dw7 - 59.4%/15.8%. PMID- 1885208 TI - Plasma membrane-associated proteins with the ability to partially inhibit perforin-mediated lysis. AB - Cytolytic lymphocytes have previously been reported to be resistant to the lytic effects of perforin. In this work, plasma membrane proteins from a CTL cell line were fractionated by HPLC, and the eluted fractions were collected based on their ability to inhibit perforin-mediated hemolysis. Three proteins with inhibitory activity were thus purified, the serine esterase MCSP-3/granzyme F and the histones H2B and H3. A commercial source of H2B was able to potently inhibit perforin-mediated lysis, and it was confirmed by FACS analysis that H2B is in fact present on the surface of cytolytic cells. However, H2B was also found on the surface of perforin-susceptible tumor cell lines, indicating that the histones may partially inhibit perforin-mediated lysis in vitro, but that they do not represent the factor conferring specific resistance on cytolytic lymphocytes. The origin of the surface histones and the possible role of the surface MCSP 3/granzyme F are discussed. PMID- 1885209 TI - Inhibition of production and function of interleukin-6 by 1,25-dihydroxyvitamin D3. AB - 1,25-Dihydroxyvitamin D3 (1,25-(OH)2D3) has been shown to interfere with immunoglobulin production and lymphocyte proliferation in vitro. These lymphocyte functions are influenced by interleukin (IL)-6 produced by antigen presenting cells. Hence, the ability of 1,25-(OH)2D3 to interfere with the production and function of IL-6 was investigated. 1,25-(OH)2D3 and the analogue MC 903 inhibited IL-6 production by LPS-stimulated human mononuclear cells. The precursor 25-OH D3 was ineffective. Likewise, 1,25-(OH)2D3 but not 25-OH D3 inhibited rIL-6-driven as well as rIL-1 alpha/beta-driven proliferation of murine thymocytes. This effect of 1,25-(OH)2D3 was partially or totally overcome by larger concentrations of rIL-6 as well as by rIL-2 and ionomycin. Consistently, the production of IL-6 and IL-2 in rIL-1 driven thymocyte cultures were found to be reduced by 1,25 (OH)2D3. Inhibition of production and function of IL-6 may therefore be involved in 1,25-(OH)2D3-mediated regulation of lymphocyte functions in vitro. PMID- 1885210 TI - Interleukin-3 enhances cytokine production by LPS-stimulated macrophages. AB - In addition to its hematopoietic activities, interleukin-3 (IL-3) can modulate macrophage functions. We have studied the production of interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis factor (TNF) by mouse peritoneal macrophages triggered by lipopolysaccharide (LPS) in the presence or absence of IL-3. Interleukin-3 at the concentration used (i.e., 100 U/ml) did not induce the production of any cytokines, whereas it enhanced significantly the secretion of IL-1, IL-6 and TNF by LPS-stimulated macrophages. The synergistic activity of IL 3 was observed over a wide range of Escherichia coli or Salmonella enteritidis LPS concentrations. No additive effect was noticed between IL-3 and granulocyte/macrophage colony-stimulating factor (GM-CSF), another factor able to enhance LPS-induced IL-1 production. Thus, IL-3 can potentiate the inflammatory response induced by endotoxin from Gram-negative bacteria through a potentiation of cytokine production. PMID- 1885211 TI - Sex differences in primary humoral responses of albino rats to human serum albumin. AB - Primary humoral responses to human serum albumin, with or without concomitant Freund's adjuvant, were determined for over 300 male and female Wistar albino rats. Groups of female rats always displayed significantly more antibody production than males. Without adjuvant only 70% of the males responded compared to 99% of the females. When the antigen was accompanied by adjuvant, more than 95% of both sexes responded. Whereas without adjuvant the female response was only twice that of the males, adjuvant facilitated the response to a factor of 10 greater than the males. Both the gender and adjuvant effect each accounted for about 16% of the variance in the measurements of antigen binding capacity. Post weaning castration did not stimulate the gender differences; there were no group differences in ABC at the extremes of estrus-related ambulatory cycles. PMID- 1885212 TI - Acetylcholinesterase from Schistosoma mansoni: immunological characterization. AB - The enzyme acetylcholinesterase (AChE) is present in the trematode Schistosoma mansoni, which infects humans and causes a severe disease called schistosomiasis or Bilharzia. We have purified this enzyme and raised polyclonal antibodies against it. The specificity of these antibodies against the schistosome enzyme was demonstrated by their capacity to precipitate exclusively AChE activity from cercariae extract and to recognize the 8S molecular form of the parasite's AChE. On the other hand, they did not cross-react at all with AChE from human erythrocytes. By employing immunogold electron microscopy, AChE was located on the surface, in the membranal bodies of the tegument and in the muscles of schistosomula. The antibodies raised against the purified AChE of S. mansoni are of protective value, as they led to efficient complement-mediated killing of schistosomula in vitro. It was also demonstrated that antibodies specific towards S. mansoni AChE are present in the sera of mice and of human patients infected with the parasite, suggesting that this enzyme partakes in the immune response towards the parasite during infection. These cumulative data, particularly the schistosomicidal activity of the antibodies and their lack of cross-reactivity with human AChE, are of significance in the consideration of the S. mansoni AChE for vaccination purposes. PMID- 1885213 TI - HIV-1: seven facets of functional molecular mimicry. AB - Molecular mimicry, where structural properties borne by a pathogen "imitate" or "simulate" molecules of the host, is shown to take make different forms in the molecular biology of the human immunodeficiency virus type 1 (HIV-1). There is considerable evidence that a number of important immunopathologic processes are incited by HIV-1 infection, due to molecular mimicry. Accordingly, a systematic review of this evidence is intended to define the fundamental immunopathogenic properties of this virus in terms relevant to the science of acquired immunodeficiency syndrome (AIDS) susceptibility, prevention, and treatment. PMID- 1885214 TI - Identification of a 200-kDa glycoprotein antigen of Saccharomyces cerevisiae. AB - SDS-PAGE analysis of the soluble proteins of the yeast Saccharomyces cerevisiae revealed a single predominant moiety of apparent size 200 kDa which was strongly periodic acid Schiff-positive. In immunoblotting experiments, human sera containing anti-S. cerevisiae antibodies were reactive only with this glycoprotein (gp200); this was demonstrated using sera containing IgG and IgA isotype-specific anti-S. cerevisiae antibodies. The antigenicity of gp200 was substantially reduced by periodate treatment. These results show that gp200 is a major glycoprotein antigen of S. cerevisiae which is immunogenic in man. PMID- 1885215 TI - Extracellular phospholipase A2 secretion is a common effector pathway of interleukin-1 and tumour necrosis factor action. AB - Inflammatory processes are characterized by increased levels of extracellular phospholipase A2 (PLA2) and cytokines such as interleukin 1 (IL-1) and tumour necrosis factor (TNF). IL-1, TNF and PLA2 share a number of proinflammatory, arthritogenic effects. The sequential induction, first of the cytokines followed by PLA2, suggests that these cytokines may regulate synthesis and secretion of PLA2. To test this postulate, foetal rat calvarial bone-forming cells (FRCC) were treated with recombinant human IL-1 and TNF and extracellular PLA2 release was quantitated. Both IL-1 and TNF induced the de novo synthesis of PLA2 in a concentration-dependent manner. Continuous exposure of FRCC in primary culture to IL-1 (50 units/ml) over 15 days resulted in as much as 100-fold increase in PLA2 secretion. IL-1 (50 units/ml) added to post-confluent cultures for a 48-h pulse increased PLA2 activity 9.4-fold. The combination of IL-1 (50 units/ml) and TNF (500 units/ml) was synergistic with an observed increase in extracellular PLA2 secretion of 146-fold following a 48-h pulse. Interleukin-6, alone or in combination with IL-1 or TNF, did not further enhance PLA2 synthesis of secretion. Cytokine-induced synthesis of PLA2 was inhibited 80% by 10 microM cycloheximide but not by dexamethasone over the range of 10(-6) to 10(-8) M. FRCC derived PLA2 was neutral-active with a pH optimum of 6-7.5 and was calcium dependent with optimal activity in the presence of 2-7 mM calcium. It had absolute 2-acyl specificity using micellar phosphatidylcholine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1885216 TI - The distribution of perforin in normal tissues. AB - We describe the production of monoclonal antibodies to murine and human forms of the lymphocyte pore-forming protein (perforin, PFP, or cytolysin), a major granule-localized cytolytic mediator of CTL and NK cells. Antibodies were raised against both murine perforin purified from a CTL line, and human perforin expressed in bacteria as a fusion protein with the Escherichia coli TrpE protein. Antibodies raised against either immunogen inhibited the hemolytic activity of murine perforin, and thus may enable us to identify the pore-forming or self associative domain of perforin. One mAb, MP1, was used to study the distribution of perforin in murine tissues under physiological conditions. We found that perforin was expressed in the granular metrial gland (GMG) cells of the pregnant murine uterus, but not in other tissues examined. These results further support the view that perforin is induced only in activated cytolytic lymphocytes, and raise the question whether perforin-containing GMG cells represent an effector of a maternal immune response to the fetus. PMID- 1885217 TI - Does negative selection involve accumulation of self-reactive thymocytes in thymic rosettes? AB - Thymic rosettes, the natural associations between thymocytes and either macrophages or dendritic cells, were isolated from the thymus by collagenase digestion and unit-gravity elutriation. Rosettes from mouse strains where either the V beta 6-bearing thymocytes are deleted because of reactivity with products of the Mlsa allele of the minor lymphocyte stimulating locus, or where V beta 17a bearing thymocytes are deleted because of reactivity with IE class II MHC molecules, were compared with rosettes from appropriate control strains to test if a selective association with stromal cells preceded deletion. Rosettes from an Mlsa-bearing strain were able to stimulate an Mlsa-reactive T-hybridoma, but much of this stimulatory activity was attributable to the few B cells associated with the rosette preparations; the stromal components of the rosettes appeared to be poor presenters of Mlsa gene products. There was no enrichment of thymocytes bearing high or low levels of V beta 6 TcR in the rosettes from the Mlsa-bearing strain, which might have reflected the poor presentation by the stromal cells. However, nor was there detectable selective association of thymocytes bearing C beta 17a in the rosettes from an IE-positive mouse strain. This argues against binding and immobilisation on stromal cells as part of the deletion process, but not against the stromal cells delivering a rapid signal during a transient association, leading later to deletion. PMID- 1885219 TI - Cytokine-induced increase in liver serotonin. PMID- 1885218 TI - Expression and function of intercellular adhesion molecule 1 (ICAM-1) on rat thymic macrophages in culture. AB - The expression of intercellular adhesion molecule 1 (ICAM-1) was studied on freshly isolated rat thymic macrophages (TMF) and after their cultivation in serum-free medium using monoclonal antibody (mAb) 1A 29 and a streptavidin-biotin immunoperoxidase technique. ICAM-1 was expressed on about 80% of freshly isolated TMF. Upon cultivation, the percentage of ICAM-1+ TMF decreased to about 30-40% in 12-day-old culture. Using double immunofluorescence staining it was found that ICAM-1 was expressed both on cortical (R-MC 40+) and CMZ/medullary (R-MC 43+) macrophage subsets. ICAM-1 was up-regulated on TMF in culture by recombinant IFN gamma, IL1 and TNF-alpha and was down-regulated by dexamethasone. Syngeneic thymocytes bound to cultivated TMF in a rosette form at both 37 degrees C and 4 degrees C. IFN-gamma treatment did not increase the binding formation. The binding between thymocytes and IFN-gamma-stimulated TMF at 37 degrees C was inhibited by pretreatment of TMF with anti-ICAM-1 mAb or pretreatment of thymocytes with anti-LFA-1 mAb, indicating that ICAM-1 on TMF is one of the ligands involved in TMF/thymocyte adhesion and subsequent direct cell-cell communication. PMID- 1885220 TI - Hypertension sustains plaque progression despite reduction of hypercholesterolemia. AB - To assess the effect of hypertension on diet-induced coronary artery plaques after a return to a nonatherogenic diet, 10 cynomolgus monkeys were fed an induction regimen containing 2% cholesterol and 25% peanut oil for 6 months and then were subjected to midthoracic aortic coarctation to induce hypertension. The animals were then fed a nonatherogenic "prudent" ration for 6 additional months (hypertension-regression group). Twelve additional monkeys were fed the atherogenic diet for 6 months; six were killed (lesion-induction control group) and six were changed to the prudent diet for 6 additional months without coarctation (normotension-regression control group). At the end of the induction period, cholesterol levels averaged 744 +/- 178 mg/dl for the 22 animals and were similar for the three groups throughout the induction period. For the animals restored to the nonatherogenic diet (hypertension-regression and normotension regression groups), serum cholesterol levels fell to 486 +/- 252 mg/dl at 1 month, to 341 +/- 162 mg/dl at 2 months, and to 234 +/- 78 mg/dl at 6 months. There was no significant difference between the hypertensive and normotensive animals. Six months after coarctation, blood pressure proximal to the coarctations for the hypertension-regression group ranged from 100/60 to 220/145 mm Hg with a mean of 166/103 +/- 36/28 mm Hg. Cross-sectional area of coronary plaques was somewhat lower for the normotension-regression control group compared with the lesion-induction control group, but the difference was not significant. Plaque area was, however, markedly greater in the hypertension-regression group than in either the lesion-induction or the normotension-regression groups (p less than 0.05 for each) despite progressive reduction in hyperlipidemia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1885221 TI - Single risk factor intervention may be inadequate to inhibit atherosclerosis progression when hypertension and hypercholesterolemia coexist. PMID- 1885222 TI - Enalapril prevents cardiac fibrosis and arrhythmias in hypertensive rats. AB - To evaluate the effects of hypertension on cardiac hypertrophy, on myocardial structure, and on ventricular arrhythmias, 27 3-month-old spontaneously hypertensive rats were treated with enalapril (10 mg/kg) daily for 11 months and compared with 26 untreated control rats. Systolic arterial pressure was significantly decreased in treated rats, and at the end of the experiment, it was 199 +/- 3 mm Hg (treated) versus 237 +/- 3 mm Hg (controls) (p less than 0.001). At this time, spontaneous arrhythmias and induced arrhythmias either by programmed electrical stimulation (train of stimuli +1 or 2 extrastimuli) or by trains of eight stimuli at decreasing coupling intervals were observed in isolated heart preparations. Comparing enalapril-treated and control rats, spontaneous arrhythmias (9 of 27 versus 20 of 26, respectively; p less than 0.01), programmed stimulation-induced arrhythmias (3 of 26 versus 12 of 23, respectively; p less than 0.01), and trains of stimuli-induced arrhythmias (4 of 26 versus 14 of 19, respectively, p less than 0.001) were less frequent in the enalapril group. Left ventricular weight was decreased in treated rats by 18% (p less than 0.001). Enalapril administration diminished the fraction of myocardium occupied by foci of replacement fibrosis normally occurring in control rats by 59% (p less than 0.001). Finally, a significant correlation was found between left ventricular weight, the extent of myocardial fibrosis, and the occurrence of ventricular fibrillation. It was concluded that chronic treatment with enalapril, which resulted in attenuation of systemic arterial pressure by limiting cardiac hypertrophy and myocardial fibrosis, decreases the propensity of the heart of hypertensive rats to arrhythmogenesis. PMID- 1885223 TI - Role of endothelium-derived prostanoid in angiotensin-induced vasoconstriction. AB - To test the hypothesis that prostanoids contribute to angiotensin II-induced vascular contraction, we compared the effect of angiotensin II on isometric tension development by rings of descending thoracic aorta bathed in Krebs' bicarbonate buffer with and without indomethacin (10 microM) to inhibit cyclooxygenase, CGS13080 (10 microM) to inhibit thromboxane A2 synthesis, or SQ29548 (1 microM) to block thromboxane A2/prostaglandin endoperoxide receptors. The comparisons were made in rings of aorta taken from normotensive rats and from rats with aortic coarctation-induced hypertension at 12 days and 90-113 days after coarctation. These rings released thromboxane B2, which was found to be endothelium dependent, increased in hypertensive rats, and stimulated by angiotensin II (10(-6) M) in normotensive rats and in hypertensive rats at 12 days after coarctation. The angiotensin II (10(-6) to 10(-5)M)-induced contraction of aortic rings was increased by about 30% at 12 days after coarctation and decreased at 90-113 days after coarctation. Removal of the endothelium increased the contractile effect of angiotensin II (10(-6) M) in aortic rings of normotensive rats and hypertensive rats at 90-113 days after coarctation but decreased the effect in aortic rings of hypertensive rats at 12 days after coarctation. In rats at 12 days after coarctation, the angiotensin II (10(-6) M)-induced contraction of aortic rings with endothelium was attenuated by indomethacin and SQ29548 but not by CGS13080. These data suggest that a prostanoid-mediated and endothelium-dependent mechanism of vasoconstriction contributes to the constrictor effect of angiotensin II in aortic rings of rats in the early phase of aortic coarctation-induced hypertension. PMID- 1885224 TI - Interleukin-2 and spontaneous hypertension. AB - There are conflicting reports with regard to the antihypertensive of interleukin 2 in the spontaneously hypertensive rat. Recently, the original claim of a normalization of arterial pressure in the spontaneously hypertensive rat after a single administration of interleukin-2 has been disputed. Therefore, the present study was performed to determine whether the administration of interleukin-2 was effective in attenuating both the development and maintenance of hypertension in the spontaneously hypertensive rat. Both young prehypertensive spontaneously hypertensive rats and adult spontaneously hypertensive rats with established hypertension received a single subcutaneous dose of 5,000 units/kg human recombinant interleukin-2. Arterial pressure was monitored at weekly intervals in both control and treated animals by the tail-cuff technique. Interleukin-2 administered as a one time single injection had no effect on the development of hypertension in the young animals or on the maintenance of hypertension in the adult animals. Interleukin-2 also was administered as a continuous infusion via osmotic minipumps at dose levels of 5,000 and 50,000 units/kg/wk to both young and adult spontaneously hypertensive rats. Continuous administration of interleukin-2 also had no effect on the development or maintenance of spontaneous hypertension. Therefore, this study firmly demonstrates that interleukin-2 has no effect on the onset or maintenance of hypertension in the spontaneously hypertensive rat. PMID- 1885225 TI - Parathyroid hormone, platelet calcium, and blood pressure in normotensive subjects. AB - Relations between platelet cytosolic calcium, parathyroid hormone, and blood pressure were investigated in 91 normotensive subjects: 47 men and 44 women ranging in age from 24 to 70 years. The men had higher mean arterial blood pressure, serum creatinine, and body mass index than the women. Serum total calcium, plasma ionized calcium, and parathyroid hormone (measured as both intact hormone and mid-molecule fragment) were not different between men and women; however, serum phosphate was higher in women than in men. Basal platelet cytosolic calcium was higher in men than in women (113.7 +/- 1.9 versus 105.9 +/- 1.7, respectively; p less than 0.01), but there was no difference in the peak platelet cytosolic calcium responses to thrombin between the two groups. In the combined group of male and female subjects, platelet cytosolic calcium correlated with diastolic blood pressure and mean arterial pressure (r = 0.37, p less than 0.001 and r = 0.32, p less than 0.01, respectively). Intact parathyroid hormone correlated with systolic and mean arterial blood pressure (r = 0.41, p less than 0.001 for both). Age correlated with both systolic blood pressure (r = 0.40, p less than 0.001) and intact parathyroid hormone (r = 0.51, p less than 0.001). When multiple regression analysis was performed using mean arterial pressure as the dependent variable, platelet cytosolic calcium and intact parathyroid hormone maintained significant correlations with mean arterial pressure. Platelet cytosolic calcium did not correlate with intact parathyroid hormone. These results suggest that both platelet cytosolic calcium and intact parathyroid hormone are associated with blood pressure regulation in normotensive subjects. However, the influences of these two factors on blood pressure are not interrelated. PMID- 1885226 TI - Sodium-lithium countertransport and hypertension in Rochester, Minnesota. AB - The objectives of the present study were to determine whether increased sodium lithium countertransport is associated with essential hypertension in the general Caucasian population and to determine whether this association is independent of the effects of gender, age, body size, and plasma lipids. We studied 543 men and 589 women from the population of Rochester, Minnesota. Mean sodium-lithium countertransport was higher in hypertensive than in normotensive subjects in men (370 +/- 147 [mean +/- SD] versus 315 +/- 110 mumol/l red blood cells [RBC]/hr, p less than 0.001) and in women (339 +/- 114 versus 269 +/- 92 mumol/l RBC/hr, p less than 0.001). Interindividual differences in plasma triglycerides, body mass index (wt/[ht]2), and plasma total cholesterol explained 13.0% of sodium-lithium countertransport variation in men (p less than 0.001) and 20.2% in women (p less than 0.001). Age did not predict additional sodium-lithium countertransport variation in either gender. Slopes of the regressions of sodium-lithium countertransport on plasma triglycerides, body mass index, and plasma total cholesterol did not differ between diagnostic groups in men (p = 0.31) or in women (p = 0.29). After adjustment to remove sodium-lithium countertransport variation attributable to these covariates, mean sodium-lithium countertransport remained significantly higher in hypertensive than in normotensive subjects in men (354 +/- 139 versus 319 +/- 104 mumol/l RBC/hr, p less than 0.01) and in women (311 +/- 103 versus 278 +/- 83 mumol/l RBC/hr, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1885228 TI - Quantitative analysis of the 24-hour blood pressure and heart rate patterns in young men. AB - To characterize the normal nycterohemeral blood pressure and heart rate profiles and to delineate the relative roles of sleep and circadian rhythmicity, we performed 24-hour ambulatory blood pressure monitoring with simultaneous polygraphic sleep recording in 31 healthy young men investigated in a standardized physical and social environment. Electroencephalographic sleep recordings were performed during 4 consecutive nights. Blood pressure and heart rate were measured every 10 minutes for 24 hours starting in the morning preceding the fourth night of recording. Sleep quality was not significantly altered by ambulatory blood pressure monitoring. A best-fit curve based on the periodogram method was used to quantify changes in blood pressure and heart rate over the 24-hour cycle. The typical blood pressure and heart rate patterns were bimodal with a morning acrophase (around 10:00 AM), a small afternoon nadir (around 3:00 PM), an evening acrophase (around 8:00 PM), and a profound nocturnal nadir (around 3:00 AM). The amplitude of the nycterohemeral variations was largest for heart rate, intermediate for diastolic blood pressure, and smallest for systolic blood pressure (respectively, 19.9%, 14.1%, and 10.9% of the 24-hour mean). Before awakening, a significant increase in blood pressure and heart rate was already present. Recumbency and sleep accounted for 65-75% of the nocturnal decline in blood pressure, but it explained only 50% of the nocturnal decline in heart rate. Thus, the combined effects of postural changes and the wake-sleep transition are the major factors responsible for the 24-hour rhythm in blood pressure. In contrast, the 24-hour rhythm of heart rate may reflect an endogenous circadian rhythm, amplified by the effect of sleep. We conclude that modulatory factors different from those controlling nycterohemeral changes in blood pressure influence the 24-hour variation in heart rate. PMID- 1885227 TI - Sodium-lithium countertransport and cardiorenal abnormalities in essential hypertension. AB - The rate of red blood cell sodium-lithium countertransport is elevated only in a subgroup of patients with essential hypertension. We have therefore compared renal and cardiac function and morphology in two groups of hypertensive patients with high (n = 23) or normal (n = 22) sodium-lithium countertransport (mean +/- SEM: 0.61 +/- 0.10 versus 0.29 +/- 0.07 mmol/l red blood cells.hr). The two groups were similar in age, sex distribution, body mass index, smoking habit, duration of hypertension, and actual levels of untreated blood pressure. Hypertensive patients with elevated sodium-lithium countertransport activity showed elevated glomerular filtration rate (118 +/- 2 versus 109 +/- 2 ml/min.1.73 m2; p less than 0.001), albumin excretion rate (23 +/- 3 versus 14 +/ 2 micrograms/min; p less than 0.001), larger kidney volume (250 +/- 15 versus 203 +/- 13 ml.1.73 m2; p less than 0.01), lower lithium clearance rate (26.7 +/- 0.3 versus 28.9 +/- 0.3 ml/min.1.73 m2; p less than 0.01), and higher total body exchangeable sodium (2,716 +/- 33 versus 2,485 +/- 41 mmol.1.73 m2; p less than 0.01). Left ventricular mass index (139 +/- 6 versus 119 +/- 6 g/m2; p less than 0.05), relative wall thickness (0.39 +/- 0.05 versus 0.29 +/- 0.04 cm; p less than 0.001), and left posterior wall plus intraventricular septum thickness (2.02 +/- 0.04 versus 1.76 +/- 0.03 cm; p less than 0.05) were also higher in patients with high sodium-lithium countertransport. Hypertensive patients with normal sodium-lithium countertransport had renal and cardiac parameters similar to those of a normotensive control group (n = 21) except for a higher glomerular filtration rate and left ventricular mass index.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1885229 TI - Postexercise hypotension is not sustained in normal and hypertensive humans. AB - Blood pressure falls after a single session of exercise. The duration for which this fall in blood pressure persists is not known. Sustained hypotension after a single session of exercise may have important implications in the treatment of patients with mild hypertension. We studied 24 subjects (12 normotensive subjects and 12 patients with mild or borderline hypertension). Blood pressure was measured in the laboratory for 30 minutes before and for an hour after graded bicycle exercise to maximal voluntary capacity. Subjects then left the hospital and measured their blood pressures at home (three measurements every 2 hours) following a strict measurement protocol for the rest of the day (usually between 8 and 12 hours). These home blood pressure measurements were compared with home blood pressure measurements recorded at the same times on a nonexercise control day. At 30 minutes after the graded maximal exercise test, the hypertensive patients experienced a fall in blood pressure from 142 +/- 3.5/93 +/- 6.5 mm Hg (mean +/- SEM) to 124 +/- 4.5/79 +/- 2.8 mm Hg (p less than 0.01). For the normotensive subjects, blood pressure after exercise fell from 117 +/- 3.1/70 +/- 2.1 mm Hg to 109 +/- 3.1/62 +/- 2.8 mm Hg (p less than 0.01). Despite these striking blood pressure reductions for the second half hour after exercise, blood pressure measurements recorded at home were not significantly different on the exercise and control days in either group. We conclude that although a single bout of exercise lowers blood pressure for a short (1-hour) period, this hypotension is not sustained. PMID- 1885230 TI - Adenosine attenuates the response to sympathetic stimuli in humans. AB - The effect of adenosine on the forearm vasoconstrictor response to alpha adrenergic and sympathetic stimulation was studied in healthy volunteers. During a predilated state achieved by infusion of sodium nitroprusside into the branchial artery, subsequent infusion of norepinephrine induced a mean increase in forearm vascular resistance of 571%, whereas this response was only 270% when an equipotent vasodilator dose of adenosine was used instead of sodium nitroprusside (nitroprusside versus adenosine, p less than 0.05, n = 6). A comparable difference was found when the endogenous release of norepinephrine was stimulated by the local infusion of tyramine, with tyramine-induced increments in forearm vascular resistance of 438% during nitroprusside versus 93% during adenosine (n = 6, p less than 0.05). During these tyramine infusions a similar increase in the calculated forearm norepinephrine overflow occurred in the adenosine and the nitroprusside tests. In a third experiment, we demonstrated that adenosine also reduced the vasoconstrictor response to lower body negative pressure, an endogenous stimulus, of the sympathetic nervous system. During nitroprusside, lower body negative pressure induced an increase in forearm vascular resistance of 135%, whereas this was 39% during adenosine (n = 6, p less than 0.05). We conclude that adenosine attenuates the response to sympathetic nervous system-mediated vasoconstriction in humans, and that this effect may at least partly be explained by a postsynaptic inhibition of alpha-adrenergic vasoconstriction. Therefore, we think that adenosine may be an important endogenous modulator of sympathetic nervous system activity in humans. PMID- 1885231 TI - Intrahypothalamic clonidine infusion prevents NaCl-sensitive hypertension. AB - We have previously shown that dietary NaCl supplementation increases blood pressure and sympathetic nervous system activity in association with decreased norepinephrine release and increased alpha 2-adrenergic receptor number in the anterior hypothalamic area of salt-sensitive spontaneously hypertensive rats (SHR S) but not in salt-resistant spontaneously hypertensive rats (SHR-R) or Wistar Kyoto (WKY) rats. Further, acute microinjection of clonidine into the anterior hypothalamic area produced depressor responses that were augmented by high salt feeding in SHR-S but not in SHR-R or WKY rats. The current study tested the hypothesis that chronic infusion of clonidine into the anterior hypothalamic area prevents salt-sensitive hypertension in SHR-S. Beginning at age 7 weeks, immediately before initiation of 1% or 8% salt diets, clonidine (2 ng/min) or saline vehicle was infused into the anterior hypothalamic area or femoral vein of male SHR-S via osmotic minipump for 20 days. In SHR-S fed an 8% salt diet, chronic microinfusion of clonidine into the anterior hypothalamic area offset the hypertensive effect of the dietary salt supplementation and reduced the enhancing effects of dietary salt on left ventricular weight and plasma norepinephrine levels. In contrast, chronic microinfusion of clonidine into the anterior hypothalamic area did not significantly affect any of these measures in 1% salt fed SHR-S. Intravenous infusion of clonidine at the rate used for the anterior hypothalamic area infusion did not alter any of these measures in 8% salt-fed SHR S.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1885232 TI - [Can the onset of periodontal disease be predicted?]. PMID- 1885233 TI - [Disinfection and sterilization methods for hand pieces, angle pieces and turbines. Updated program]. PMID- 1885234 TI - [Are there really physiologic nipples?]. PMID- 1885235 TI - [Treatment of severe vertical overbite with help of apparatus with built in treatment evaluation]. PMID- 1885237 TI - [Pont's index--a discussion]. AB - When comparing orthodontic textbooks from various countries Pont's Index appears to have played a relatively important role in Germany. In the USA a marked shift in treatment concept came up during the forties, in that the maintaining of pre treatment dental arch form--specifically in the lower jaw--now was considered to be important for reasons of stability. Later research findings have supported this concept. In view of present knowledge, strong doubts are expressed regarding the justification for the use of Pont's Index in clinical practice, in teaching as well as in communication with the Health Insurance. PMID- 1885236 TI - [Experiences with surgically supported maxillary expansion]. AB - The experience of a method for surgical support of a rapid maxillary expansion is described. The attached region of the maxillary zygomatic process and the dorsal and middle part of the hard palate are osteomized. The results of 18 patients are demonstrated. Almost all patients underwent surgical correction of the sagittal and/or vertical jaw discrepancies later. This surgical-orthodontic expansion proved to be an effective and low pain method for preoperative correction of transverse maxillary deficiencies and facilitated the subsequent skeletal surgery. After the treatment mentioned above in cases with a correct position of the maxilla in relation to the skull base a Le-Fort-I-Osteotomie was not necessary. PMID- 1885238 TI - Treatment of hepatic insufficiency based on cellular therapies. PMID- 1885239 TI - Use of the ultrafiltrate obtained in two-chamber (PFD) hemodiafiltration as replacement fluid. Experimental ex vivo and in vitro study. AB - PFD (Paired Filtration Dialysis) is the only hemodiafiltration (HDF) technique in which the ultrafiltrate (UF) is continuously available not mixed with the dialysate. As with all convective or prevailingly convective techniques, a replacement fluid is necessary in an amount equal to the difference between the UF and the desired weight loss. This replacement fluid (R) must have an adequate electrolytic balance (Na+, Ca++, and buffer), and must be sterile and pyrogen free. Using an uncoated adsorbent charcoal cartridge, we "regenerated" the UF obtained in PFD, eliminating the small (except for urea, which was later eliminated by diffusion in the dialyzing section of the PFD system) and the medium-to-large molecules (vit B12 and myoglobin in vitro and beta-2 microglobulin (B2m) and (hANP) in vivo), but not the electrolytes and the endogenous bicarbonate, so as to verify its possible use as R. This technique, experimentally performed in 12 patients under HDF treatment with standard PFD, with a total mean UF of 9650 +/- 875 ml and the use of 130 g of uncoated charcoal, produced a solution with the following composition: Na+ 135.4 +/- 2.4 mmol/l, K+ 3.4 +/- 1.23 mmol/l, Ca++ 1.18 +/- 0.14 mmol/l, HCO3- 26.7 +/- 2.3 mmol/l, phosphates 2.88 +/- 0.81 mg/dl, urea 63 +/- 14 mg/dl, creatinine 0.08 +/- 0.02 mg/dl, uric acid 0.05 +/- 0.0 mg/dl, beta-2 microglobulin 0.5 +/- 0.5 mg/l, and hANP 4.15 +/- 5 pg/l.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1885241 TI - Computational fluid dynamics of artificial heart valves. AB - A large number of in vitro studies during the last thirty years have assessed the fluid dynamic behavior of different artificial heart valves. The present study illustrates the utility of the Finite Element Method for fluid dynamic evaluation of prosthetic heart valves. The valves investigated were the Bjork-Shiley Convex Concave (curved disc), the Medtronic-Hall (flat disc) and the Carbomedics (bileaflet). These three types were chosen in order to clarify the role of different occluder geometries on global and local fluid dynamics. The Finite Element Method was used to calculate pressure and velocity fields in the fluid domain around each valve. There were significant differences, mainly in local fluid dynamics, between the three valves. The Reynolds number also plays an important role. PMID- 1885240 TI - Kidney transplantation from elderly living donors. AB - Because of the inadequate numbers of organ donors, transplant surgeons are obliged to search for new horizons. Also, traditional beliefs are changing. The shortage of organs for transplantation, has led us to try certain arrangements so that suitable elderly organ donors may be included, as in many other transplant centers. We have now done 34 kidney transplantations from living related donors, who were 60 years of age and older. Donor-specific transfusions and low-dose triple drugs were used for all recipients. The overall patient survival was 97.5% and graft survival was 85.29%. In the light of these results we conclude that elderly living donor kidneys can be used satisfactorily with low-dose triple therapy. PMID- 1885242 TI - Prosthetic heart valve evaluation in vitro: critical aspects of data comparability. AB - The technology of heart valve substitution has considerably improved in the last few years, but its reliability after implantation is still not good enough, hence the need to study new valve design and improve quality testing. Different pulse duplicators are used for heart valve testing, but the results depend very much on the system adopted and the measurement protocol. Tests on two pulse duplicators currently used at the Biomedical Engineering Laboratory at the Istituto Superiore di Sanita, Rome, are reported here. The most significant parameters for valve evaluation were measured following each system's own protocol. Attention was focused on vascular load tuning when setting up the system and on the relationship between drive unit flow waveform and valve regurgitation and energy loss measurements. Standardization criteria must be defined in order to ensure the reliable comparability of in vitro testing results. PMID- 1885244 TI - Right-left ventricular output balance in the totally implantable artificial heart. AB - Pneumatically powered artificial hearts readily accommodated the higher net stroke volumes by the right ventricle than from the left ventricle. We published that this discrepancy was approximately 8% of the left ventricular cardiac output. A variety of methods have been used to achieve balance between the right and left atrial pressures. Relatively large volume-displacement chambers (VDC) present potential problems, but do provide balance. The VDC in volumetrically coupled right-left stroke volumes was eliminated by using a small-diameter interatrial shunt (IAS). Preliminary studies demonstrated excellent balance in contracted and expanded blood volume (preload) and by hypotension and hypertension created with vasoactive drugs (afterload). At a mean aortic pressure of 120 mmHg, heart rate of 120 BPM, cardiac output of 8 L/minute and right atrial pressure of 13 mmHg, the peak IAS flow was 3.2 ml/beat in a right to left direction and 8.0 ml/beat in a left to right direction. The net left to right flow was 4.8 ml/beat. Over a wide range of preload (2 to 20 mmHg) and afterload (45 to 180 mmHg), the left atrial pressure was routinely 5 mm Hg more than the right atrial pressure. Elimination of the VDC reduces the number of components, volume, and weight of the totally implantable artificial heart. The IAS offers a simple solution to a very complex problem and provides a device that is simpler to implant and is possible to explant. PMID- 1885243 TI - Time delay compensation for closed-loop insulin delivery systems: a simulation study. AB - Closed loop insulin therapy certainly represents the best possible approach to insulin replacement. However, present limitations preclude wider application of the so-called artificial pancreas. Therefore, a thorough understanding of these limitations is needed to design better systems for future long-term use. The present simulation study was design: to obtain better information on the impact of the measurement delay of currently available closed-loop devices both during closed-loop insulin delivery and blood glucose clamp studies, and to design and test a time delay compensator based on the method originally described by O.J. Smith. Simulations were performed on a Compaq Deskpro 486/25 personal computer under MS-DOS operating system using Simnon rel. 3.00 software. There was a direct relationship between measurement delay and amount of insulin delivered, i.e., the longer the delay the higher the insulin dose needed to control a rise in blood glucose; the closed-loop response in presence of a time delay was qualitatively impaired both during insulin delivery and blood glucose clamp studies; time delay compensation was effective in reducing the insulin dose and improving controller stability during the early phase of clamp studies. However, the robustness of a Smith's predictor-based controller should be carefully evaluated before implementation in closed-loop systems can be considered. PMID- 1885245 TI - Dynamic filtration of blood: a new concept for enhancing plasma filtration. AB - We have shown previously that blood flow pulsations created by intermittent squeezing of the inlet blood line significantly increased the plasma filtration rate in membrane plasmapheresis. However, in order to avoid hemolysis, the filtration increase had to be limited to about 50%. We have now devised a more efficient pulsation generator. By properly matching the tubing compliance and the pulsation amplitude, it is possible to extract 50 ml/min of plasma from 90 ml/min of blood at 36% hematocrit with a 1000 cm2 polypropylene hollow fiber filter without hemolysis. Simultaneous recording of the time course of plasma filtration rate measured by an electromagnetic flow meter and transmembrane showed that the increase in mean plasma flow rate was due to a dynamic filtration process which prevents the establishment of concentration polarization. The transmembrane pressure (Ptm) increases over a 0.5-second interval when the tube is squeezed. The membrane responds with an increase in filtration since the concentration polarization layer takes a few seconds to build up. The Ptm then drops when the tube is released before the polarization layer has time to build up appreciably and a sudden acceleration of the blood flow (velocity spike) helps clean the membrane, reducing the polarization. Tests with bovine show that the system is very efficient in reducing membrane plugging with small area filters. PMID- 1885246 TI - Evaluation of vibrated fluidized bed techniques in coating hemosorbents. AB - A coating technique employing a vibrated fluidized bed was used to apply an ultrathin (2 microns) cellulose nitrate coating to synthetic bead activated charcoal. In vitro characteristics of the resulting coated sorbent, including permeability to model small and middle molecules, and mechanical integrity, were evaluated to determine the suitability of the process in coating granular sorbents used in hemoperfusion. Initial tests suggest the VFB-applied CN coating is both highly uniform and tightly adherent and warrants further investigation as a hemosorbent coating. PMID- 1885247 TI - Long survival in hemodialysed patients with oxalosis. PMID- 1885248 TI - Approaches to chemical dependency: chemical dependency and interactive group therapy--a synthesis. AB - Though the focus on interpersonal interaction is a powerful therapeutic factor in group therapy, traditional chemical dependency therapy groups generally fail to employ the interactional group orientation. An interactional approach can be effectively applied to alcoholics if the following guidelines are observed: (1) recovery is always accorded priority, (2) the patient accepts identification as an alcoholic, (3) anxiety is carefully modulated, (4) the proper distinction is made between what the alcoholic is and is not responsible for, (5) the therapist is thoroughly familiar with Alcoholics Anonymous language, steps, and traditions. It is important that therapists not permit misperceptions of A.A. to be used as therapy resistance and that they be able to harness the wisdom of A.A. for psychotherapeutic ends. Group therapists must also be prepared to deal with common themes arising in the treatment of the alcoholic patient: idealization, devaluation, externalization, defiance, grandiosity, conning, and avoidance. PMID- 1885249 TI - Dilemmas and countertransference considerations in group psychotherapy with adult children of alcoholics. AB - This article will explore special leader issues that emerge in psychodynamically oriented therapy groups with adult children of alcoholics. Particular focus will be on countertransference feelings that get stirred up in group leaders and techniques for dealing with some of these special dilemmas. Specific issues include (a) assumption of sameness between the therapist and the patient (the therapist assuming that he or she "understands" because of having also grown up in an alcoholic family); (b) the "will to restore," which may be destructive when the therapist, whose own self-esteem is dependent on the patient's progress in therapy, forces a "rush to recovery" on the patient; (c) other personal issues in the life of the therapist that may also resonate with experiences of the patient; (d) "countertransference goodness and availability" as it affects therapists' abilities to set reasonable limits on their patients, as well as reasonable expectations for themselves; and (e) special issues regarding therapist transparency and self-disclosure. PMID- 1885250 TI - Combined individual and group psychotherapy: guidelines at the interface. AB - The development of combined individual and group psychotherapy is split between the "separationists" and the "integrationists" with regard to therapists' handling of the interface between the individual and group sessions. To bridge the impasse, a high-benefit--low-risk series of guidelines is offered for therapists that includes techniques for analyzing patients' "cross-references" to the other component modality. The four guidelines provide for a harmonious balance that preserves the confidentiality of the individual sessions vis-a-vis the group, while enhancing the group interaction rather than draining it. The therapist guidelines maximize patient initiative in integrating parts of the self expressed in the individual and group sessions, while employing the least intrusive methods necessary to best integrate the processes into a unified combined modality. PMID- 1885251 TI - Emergent themes and roles in short-term loss groups. AB - Clinical observations regarding themes and roles that are characteristic of short term, psychoanalytically oriented therapy groups for loss patients are presented. They reflect aspects of both the therapy and the patients. Themes refer to the content of a recurrent conflict in the group. They include trust, survivor guilt, mortality, and termination. Roles refer to a set of patient behaviors that represent a shared conflict. They include the apparition, monk, professor, professional nurturer, emotional conductor, and cruise director. Challenges that the themes and roles present to the therapist and clinical guidelines for addressing them are offered. Awareness of characteristic themes and roles and possible therapist responses are regarded as important parts of the preparation and training of therapists who plan to conduct short-term loss groups. PMID- 1885252 TI - Interaction analysis: meaningless in the face of relevance. AB - Interaction analysis has become a standard tool for process-oriented research. Although now a researcher has a choice of instruments, the majority of these are based on the same concept of communication: the sender-receiver model. Communication is treated as a discrete and encoded process that progresses uniformly in time. We critically discuss these assumptions and the limits they put on communication research. It is asserted that instruments for interaction analysis based on the sender-receiver model restrict themselves to the more superficial levels of interaction and are unable to register the more significant events. Therefore they cannot account for a very essential feature of the communication process, namely the creation of meaning. Alternative options are discussed. PMID- 1885254 TI - Process variables mediating change in intensive group therapy training. AB - This investigation is based on over 400 American Group Psychotherapy Association members involved in 41 intensive, two-day training experiences for mental health professionals. The participants completed a questionnaire immediately after their group sessions to evaluate the process and leadership variables that contributed to a constructive learning experience. A similar questionnaire was mailed to participants three to four months later to explore the impact of training on group interventions within their clinical practices. One third of the trainees responded to the follow-up survey. Overall, the findings suggest that successful outcomes are related to a range of group processes, such as self-disclosure, feedback, and interpersonal support, as well as personal qualities and technical expertise modeled by the leaders of the training groups. Both the immediate and delayed assessments demonstrate that the groups were regarded as highly valuable learning opportunities. PMID- 1885253 TI - A comparison of curative factors in different types of group psychotherapy. AB - The authors have constructed a Dutch version of Yalom's "Questionnaire for Curative Factors." This Dutch version has been administered to 134 participants of 22 psychotherapy groups in various psychiatric services in the Netherlands. Results concerning validity and reliability of the instrument are presented, as well as concerning the homogeneity of the hypothesized "factors." Differences between types of groups and categories of group members were tested by means of techniques of analysis of variance (ANOVA). Multiple regression analysis was applied in order to detect variables of differential qualities on one or more factors. Only the factor identification, neglected in literature on curative factors, was highly predictable. PMID- 1885255 TI - Group treatment of the hyperventilation syndrome. AB - Hyperventilation (hv) is increasingly recognized as being significant in a number of psychological and medical conditions. The core of treatment for hv is breathing retraining, usually on an individual basis. This article describes a group therapy for breathing retraining for patients with hv-induced panic reactions. An analysis of group process suggests that such treatment is helpful in ways impossible for individual retraining and that further exploration of this modality is warranted. PMID- 1885256 TI - Plasma catecholamine levels and lipid mobilization induced by yohimbine in obese and non-obese women. AB - Oral yohimbine administration (0.2 mg/kg) induced lipid mobilization (increase in plasma non-esterified fatty acids, NEFA) in fasting non-obese women (body mass index BMI = 20.2 +/- 0.5, age 35.5 +/- 2.7 years) without significant action on plasma glucose, insulin levels, heart rate or blood pressure during the time course of the experiment (240 min). Plasma norpinephrine (but not epinephrine) concentrations were increased (100 percent) after oral yohimbine administration. Oral administration of propranolol (40 mg, 60 min before yohimbine) reduced the lipid-mobilizing action of yohimbine (70 percent) during the 60 min following its administration and then totally suppressed its effect until the end of the experimental period (180 min). In fasting obese women (BMI = 36.4 +/- 2.1, age 37 +/- 3.6 years), yohimbine provoked an increase in plasma NEFA levels which was not markedly different from that observed in non-obese subjects. It had no significant effect on plasma glucose, insulin levels, heart rate or blood pressure. Plasma norepinephrine increased in the same proportions. The lipid mobilizing effect of yohimbine in women is mainly attributable to the increase in synaptic norepinephrine with a resultant increment in lipolysis by beta adrenergic agonism. In the standard fasting conditions (12 hours) the blockade of the antilipolytic fat cell alpha 2-adrenoceptors seems to be a minor component of the lipomobilizing effect of yohimbine. Morever, when compared with non-obese women, the lipomobilizing effect of yohimbine is not enhanced in obese women. PMID- 1885257 TI - Peripheral mechanisms of thermogenesis induced by ephedrine and caffeine in brown adipose tissue. AB - The peripheral mechanisms by which ephedrine and caffeine influence thermogenesis were investigated in innervated rat interscapular brown adipose tissue (IBAT) by assessing its rate of oxygen consumption (MO2) in vitro. Dose-response measurements with tissues from intact or sympathectomized (6-OHDA) animals indicate that the thermogenic effects of low concentrations of ephedrine and also of caffeine are entirely dependent upon the presence of intact sympathetic nerve endings, and thus depend on presynaptic mechanisms. Direct postsynaptic stimulation of thermogenesis is only apparent at much higher concentrations, namely greater than 1 microM for ephedrine and greater than 2mM for caffeine. At subminimal concentrations that neither ephedrine nor caffeine influenced basal tissue respiration, they induced a 4-5-fold increase in basal MO2 when administered in combination, a synergistic response prevented by pre-treatment of the rat with 6-OHDA. Synergistic increases in IBAT respiration were also obtained when subminimal concentration of ephedrine was added to 3-propylxanthine (a specific inhibitor of phosphodiesterase), to 8-phenyltheophylline (a potent adenosine receptor antagonist) or to adenosine deaminase (for enzymatic inactivation of endogenous adenosine). Conversely, the marked synergism in thermogenic response with ephedrine + caffeine was reduced in the presence of 2 chloroadenosine (an adenosine analogue). In tissues from fasted rats, the ephedrine + caffeine synergism in thermogenic response, although attenuated, was nevertheless present. These studies therefore demonstrate that ephedrine, at doses comparable with therapeutic use, stimulates thermogenesis in BAT via sympathetically released NA. In addition, a synergistic interaction between caffeine and ephedrine on BAT thermogenesis is explained by ephedrine's enhancement of sympathetic neuronal release of NA, together with caffeine's dual ability to antagonize adenosine and to inhibit cellular phosphodiesterase activity. PMID- 1885258 TI - Levels of acylation stimulating protein in obese women before and after moderate weight loss. AB - Acylation stimulating protein (ASP) is a small (MW 14,000) basic (pI 9.0) protein which has only recently been purified from human plasma. Since ASP is the most potent known stimulant of triglyceride synthesis in human adipose tissue, the present study was designed to determine if plasma ASP was elevated in patients with moderate obesity, and if so, whether this level changed with weight loss. Fasting plasma ASP levels were determined by competitive ELISA immunoassay in 10 obese women before weight loss, immediately after weight loss, and 3 months after maintaining weight reduction. Their plasma ASP results were compared to 17 age and sex-matched lean controls. With weight loss, plasma ASP decreased significantly: 19.6 +/- 10.7 mg/dl before weight loss vs 15.0 +/- 9.5 mg/dl after weight loss vs 13.8 +/- 7.7 mg/dl 3 months after being weight stable, P less than 0.05 initial vs final value. Nevertheless, plasma ASP was significantly higher than the control value at all three times. Thus, before weight loss, the average ASP in the obese group was four times that in the control group (19.6 +/- 10.7 vs 5.1 +/- 3.6 mg/dl, P less than 0.0005) while even 3 months after weight loss, it remained almost three times above the control group (13.8 +/- 7.7 vs 5.1 +/- 3.6 mg/dl, P less than 0.0005). The data suggest, therefore, that an elevated plasma level of ASP is common in obesity, that the level of plasma ASP may reflect the fat cell mass present in an individual, and raises the possibilities that ASP may play a role in initiation or maintenance of the obese state. PMID- 1885259 TI - Energy need in childhood and adult-onset obese women before and after a nine month nutrition education and walking program. AB - The effect of a 9-month nutrition education and walking program on total calorie need, resting metabolic rate (RMR), thermic effect of food (TEF), body composition, and activity level was determined in seven women (28-41 years of age) with childhood-onset obesity (CO) and eight women (29-42 years of age) with adult-onset obesity (AO). A 3-week testing period was conducted before and after the 9-month program during which all subjects were fed a controlled, weight maintaining metabolic diet which was used to determine daily calorie need. Body composition, RMR, and TEF were measured during the second and third weeks of both 3-week testing periods. Body weight decreased significantly for CO (mean -5.7 +/- 9.3 kg) and AO (mean -3.3 +/- 6.2 kg), but fat-free mass (FFM) was unchanged. When comparing pre to post data, mean total calorie need increased by 2.9 percent for CO and 3.1 percent for AO (P greater than 0.05), RMR decreased 3.6 percent for CO and 2.8 percent for AO (P less than 0.05), and TEF increased 11 percent for CO and 50 percent for AO (P less than 0.05). Time spent in light and moderate level activity increased significantly from pre to post. The increase in activity and TEF more than compensated for the slight decrease in RMR (mean -55 kcal/day), contributing to an overall increase in daily energy need (mean = 74 kcal/day) at the end of the program, even for the six women who lost greater than 5 kg body weight. PMID- 1885260 TI - Aspirin potentiates the effect of ephedrine on the thermogenic response to a meal in obese but not lean women. AB - The effect of ephedrine (30 mg) and aspirin (300 mg) on the acute thermogenic response to a liquid meal (250 kcal) was investigated in lean and obese women (n = 10 each group). Resting metabolic rate (RMR) was measured prior to each of the following treatments: meal only (M), meal plus ephedrine (ME) or meal plus ephedrine and aspirin (MEA). Eight post-treatment measurements of metabolic rate were made over a total of 160 minutes. Rise in post-treatment metabolic rate was compared to the baseline RMR. Following the M treatment, the mean increase in metabolic rate was 0.17 +/- 0.01 and 0.13 +/- 0.02 kcal/min in the lean and obese groups respectively, with the corresponding rises being 0.21 +/- 0.02 and 0.19 +/ 0.02 kcal/min following the ME, and 0.23 +/- 0.03 and 0.23 +/- 0.01 kcal/min following the MEA. The increase in post-prandial thermogenesis with the ephedrine or ephedrine plus aspirin was significant in the obese group (P less than 0.03 and P less than 0.001 respectively) but not the lean. Furthermore, the post treatment rise in metabolic rate, following the MEA treatment compared to the ME, was significantly greater for the obese group (P less than 0.05) but not the lean. It was concluded that aspirin potentiates the stimulatory effect of ephedrine on the thermogenic response to a meal in obese but not lean women. PMID- 1885261 TI - Effects of weight cycling caused by intermittent dieting on metabolic rate and body composition in obese women. AB - The effects of repeated periods of weight loss and regain on metabolic rate and body composition were investigated in 11 obese women (mean weight 81.98 kg, height 1.61 m, body mass index 31.44 kg/m2) studied for 18 weeks through three consecutive cycles of 2 weeks dieting followed by 4 weeks ad libitum eating. Weight loss was achieved by a very low energy diet (1861 kJ/day). Basal metabolic rate (BMR) was measured by whole-body indirect calorimetry and body composition by a variety of standard in vivo methods. During the three diet periods mean weight losses were 4.44, 3.29 and 2.98 kg although the mean overall weight loss from week 0 to 18 was only 5.93 kg. The proportion of weight lost as fat was estimated as between 67 and 105 per cent of the weight lost depending on the body composition methodology employed. Absolute BMR decreased in response to dieting by 545, 285 and 286 kJ/day. When corrected for body weight and FFM only the decreases in the first diet period were significant (P less than 0.05 and P less than 0.001 respectively). BMR had returned to normal following each 4-week ad libitum period and by the end of the study absolute BMR and BMR/kg FFM had not changed significantly, despite a significant loss of weight. Consequently BMR/kg was increased (P less than 0.01), indicative of the loss of adipose tissue. We have found no evidence in this group of obese women that weight cycling leads to a progressive decrease in BMR or increase in the proportion of body fat. PMID- 1885262 TI - Energy turnover and heat exchange in mature lean and obese Zucker rats acutely exposed to three environmental temperatures for 24 hours. AB - Differences between lean (FA/?, n = 6) and obese (fa/fa, n = 6) mature male Zucker rats' energy turnover and heat storage were compared during a 24-h period when the animals were exposed to ambient temperatures of 30, 15 or 5 degrees C. Energy turnover was examined through measurements of heat production rates via indirect calorimetry and heat loss rates via direct calorimetry. Heat storage rates were calculated as the difference between heat production and heat loss rates. Predicted heat storage rates were also calculated as the product of the change in core temperature and the calculated specific heat of the animal based on body composition (carcass) analysis. A minimal heat loss rate was determined for each animal representing a period of least activity. Various comparisons were made: between groups (lean/obese), temperature (30, 15, 5 degrees C), calorimetry method (indirect/direct), period (light/dark), heat storage (experimental/predicted), and minimal heat loss. Immediately before a test, pretest weight and colonic temperature were obtained. Then, the animal was placed into the calorimeter chamber and remained there unrestrained for 24 h. Normal light/dark periods were maintained. On removal from the calorimeter, core temperature and body weight measurements were again obtained. Upon completion of all tests, body composition was analyzed and surface area determined. Energy turnover, i.e. both heat production and heat loss in the lean and obese animals differed among the 30, 15 and 5 degrees C exposures. The obese animals had relatively greater heat production rate and heat loss rate (kcal/day or kcal/kg (FFM)/day than the lean animals at 30, 15 and 5 degrees C. But, on a relative basis, the increments in heat production in the cold environments were greater for the lean animals. Both the lean and obese animals tended to be more active during the dark period when at 30 degrees C, but the difference was less at 15 degrees C and even less at 5 degrees C. Experimental heat storage rates did not differ significantly from predicted values at any of the temperatures with the possible exception of the animals at 5 degrees C. It was concluded that the mature obese Zucker rats had no major discernible defect in thermoregulation as revealed by rates of heat production and loss, although three of the obese rats did elicit a drop in colonic temperature during exposure to 5 degrees C, i.e. their excessive subcutaneous adiposity and thermal insulation did not prevent a fall in colonic temperature.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1885263 TI - Body mass index and patterns of mortality among Seventh-day Adventist men. AB - This study examines the relationship between body mass index (BMI) and 26-year mortality among 8828 nonsmoking, nondrinking Seventh-day Adventist men, including 439 who were very lean (BMI less than 20 kg/m2). The adjusted relative risk comparing the lowest BMI quintile (less than 22.3) to the highest (greater than 27.5 kg/m2) was 0.70 (95 percent CI 0.63-0.78) for all cause mortality, 0.60 (95 percent CI 0.43-0.85) for cerebrovascular mortality, and 0.80 (95 percent CI 0.61 1.04) for cancer mortality. Very lean men did not show increased mortality. To assess whether the protective effect associated with low BMI is modified by increasing age, the product term between BMI and attained age (age at the end of follow-up or at death) was included as a time-dependent covariate. For ischemic heart disease mortality, age-specific estimates of the relative risk for the lowest quintile relative to the highest ranged from 0.32 (95 percent CI, 0.19 0.52) at age 50 to 0.71 (95 percent CI, 0.56-0.89) at age 90. Interaction was also seen for the next lowest quintile (22.4-24.2). There was a significant trend of increasing mortality with increasing BMI for all endpoints studied. For cancer and cerebrovascular mortality the P-values for trend were 0.0001 and 0.001 respectively. For the other endpoints the P-values were less than 0.0001. Thus, there was no evidence for a J-shaped relationship between BMI and mortality in males. While the protective effect associated with the lowest BMI quintile decreased with increasing age for ischemic heart disease mortality, it remained greater than one at all ages. The relatively large number of subjects who were lean by choice, rather than as a result of preclinical disease or smoking, may explain these findings. PMID- 1885264 TI - Physical activity and attitudes in lean and obese children and their mothers. AB - Forty pairs of biologically related mothers and children were recruited to determine (1) if differences existed in physical activity levels of obese and nonobese children and (2) if their activity or attitude toward it was influenced by maternal activity and attitudes. Ultimately, the goal was to identify whether certain maternal factors (her adiposity, activity level, and/or attitude toward activity) related to the child's adipose level. Children were classified as obese or nonobese by skinfold thickness. Mothers and children completed either the ATPA or CATPA, attitude measurement instruments. Each wore a Caltrac activity monitor for two consecutive days. No significant difference was found between obese and nonobese boys' and girls' physical activity level nor their total attitude toward physical activity. However, significant gender differences were found for the vertigo and aesthetic dimensions. When children's adiposity and gender were considered as interacting factors, differences were also found for the attitude dimensions of health and fitness, and catharsis. There were no significant relationships between child and maternal activity level, attitude toward physical activity, and adipose level. Obese and nonobese children had similar levels of physical activity and attitudes toward activity, unrelated to the maternal factors measured. Although attitudes were positive, physical activity levels for both groups were rather low -- and not likely to help in weight control efforts. PMID- 1885265 TI - Dietary-induced permanent changes in brown and white adipose tissue composition in rats. AB - We have previously observed that feeding rats a cafeteria diet causes excess weight gain and changes in tissue composition. The object of this study was to assess whether these alterations were sustained after withdrawal of the palatable diet in the rat. The results showed that the obesity was not reversed by feeding a standard diet ad libitum for five months after withdrawal of the cafeteria diet. Body weight was 26 per cent greater than in control rats and tissue composition showed permanent alterations. The excess weight of lumbar white adipose tissue was due mainly to lipid content (86 per cent) and this was also true, but to a less extent, for interscapular brown fat (59 per cent). Increased brown fat mass was a result of hyperplasia and hypertrophy, whereas increased lumbar white fat was mainly a result of hyperplasia alone. In conclusion, changes in tissue composition, particularly in fat depots, were permanent and could be ascribed to the obesity per se, and not to the diet composition. PMID- 1885266 TI - Beta-endorphin plasma levels and their dependence on gender during an enteral glucose load in lean subjects as well as in obese patients before and after weight reduction. AB - It is speculated that endogenous opioid peptides are involved in glucose metabolism and that their homeostasis might be disturbed in obesity. Despite a different response of the pancreatic beta-cells after beta-endorphin and naloxone injections between obese patients and normal weight controls, there is little knowledge concerning the direct influence of a glucose load on beta-endorphin plasma levels, especially with respect to various nutrition states. During exploration of this topic we gained further insight on the difference of basal beta-endorphin plasma levels between normal and overweight persons. We compared beta-endorphin plasma levels during an oral glucose load in 60 obese, non diabetic patients and in 20 normal weight controls. We also studied 40 of the obese patients after a weight reduction of 2.1 kg/m2. The following results were obtained: (1) Normal weight females have significantly lower (P less than 0.05) basal beta-endorphin levels compared to the male controls. This difference in gender is abolished in obesity where female and male patients do not differ in basal beta-endorphin plasma levels. Therefore, the difference between normal and overweight persons in beta-endorphin plasma levels was restricted to the subgroup of females. We suppose that former neglect of this difference in gender explains most of the so far reported discrepant results. (2) During the oral glucose tolerance test the beta-endorphin plasma values remained constant in the obese group. Despite improved insulin sensitivity after weight reduction there was still no change of beta-endorphin plasma levels both during the OGTT and when compared to the values before weight reduction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1885267 TI - Increased metabolic rate in obese women after ingestion of potassium, magnesium- and phosphate-enriched orange juice or injection of ephedrine. AB - Thirty-six obese, pre-menopausal women were studied after an overnight fast and randomized to four different regimens of metabolic stimuli: group I (n = 12), 100 ml orange juice with dissolved K- and Mg-phosphates (K, 40 mmol; Mg, 17.5 mmol; HPO4, 35 mmol); group II (n = 8), 100 ml of water with electrolytes as in group I; group III (n = 8), 100 ml of orange juice; group IV (n = 8), injection of ephedrine intravenously, 0.25 mg/kg body weight. The women in groups I, II and III were further stimulated with ephedrine as in group IV and new measurements made. Thirty minutes after the first stimulus VO2, VCO2 and energy expenditure (EE) rose significantly (13.1-16.5 per cent) in groups I and IV only. In groups I and III the blood concentrations of glucose, insulin, and C-peptide rose significantly. After the second stimulus (ephedrine i.v.) no further increase in VO2, VCO2 and EE occurred in group I, but the increases from basal values became significant in group III. In all women at baseline, whole-body potassium was significantly correlated to VO2. Serum-magnesium was negatively correlated to A/I weight (actual/ideal weight). We conclude that the addition of K- and Mg phosphates to glucose increases the postprandial thermogenesis in obese patients. PMID- 1885268 TI - Comparison of ultrasonography and oral cholecystography in biliary lithotripsy. I. Screening patients. AB - Ultrasound and oral cholecystography (OCG) are both used to evaluate candidates for biliary lithotripsy. Some investigators have suggested abandoning the OCG, believing that sufficient screening information can be obtained from ultrasound. This study compares ultrasound and OCG in assessing the size and number of gallstones, both in vitro and in vivo. In the in vitro model, 35 gallstones, divided into 20 groups, were separately suspended in dilute contrast media in a phantom, and examined by ultrasound and simulated OCG by each of three gastrointestinal radiologists. In the in vivo study, the ultrasound and OCG examinations from 53 patients were independently reviewed by three radiologists. The number and size of the stones were recorded in both studies. In the in vitro study, the stone size was measured within 2 mm of the actual size by OCG in 23/35 stones (66%) and by ultrasound in 4/35 stones (11%). The correct number of stones was determined by OCG in 19/20 groups (95%), and by ultrasound in 14/20 (70%). In the in vivo study, all readers saw the same number of stones in 40/50 (80%) patients by OCG and 33/49 (67%) patients by ultrasound. Statistical analyses revealed correlation coefficients for OCG greater than those for ultrasound in each comparison. The size of the largest stone was within 2 mm by all readers in 26/51 (51%) of patients by OCG and 20/47 (43%) patients by ultrasound. Oral cholecystography is more reliable than ultrasound for the determination of size and number of stones in patients being screened for biliary lithotripsy. PMID- 1885269 TI - Comparison of ultrasonography and oral cholecystography in lithotripsy. II. Determining retreatment. AB - Both ultrasonography (US) and oral cholecystography (OCG) are being used to evaluate patients after extracorporeal shock wave lithotripsy (ESWL) for gallstones. Criteria for retreatment after the initial ESWL are usually related to the size of the residual fragments. This study examines the efficacy of ultrasound and OCG for determining both the size and number of stone fragments in the gallbladder in an in vitro model and in patients. Ultrasonography and OCG examinations using an in vitro ESWL phantom with ten groups of stones, and on 39 patients, were reviewed independently by three radiologists to determine both the size and number of stone fragments. For the in vitro study, the three readers estimated the correct number of fragments, or the next closest range, in 87% of observations by OCG and in 43% by US. The size of the largest fragment was measured within 1 mm of its actual size in 87% of observations by OCG and 20% by US. Correlation coefficients for the mean measurements of the three readers versus the actual fragment size and number were greater for OCG than for US. For the in vivo study, the three readers agreed in 47% of the OCG versus 32% of US examinations with respect to the number of fragments, and in 65% of OCG compared to 40% of US studies with respect to size of the largest fragment. Multiple statistical analyses demonstrate that these differences are statistically significant. A discrepancy among the readers concerning whether a patient was eligible for retreatment occurred in 15% of OCG as compared to 45% of US studies. Both the in vivo and in vitro studies indicate that there is more interobserver reproducibility for OCG than for US, and that OCG is more reliable in making the decision concerning patient eligibility for retreatment following lithotripsy. PMID- 1885270 TI - Time course of satisfaction of search. AB - "Satisfaction of search" (SOS) refers to the effect in which a second lesion remains undetected after detection of another lesion on the same radiograph. The objective of this study was to clarify our understanding of SOS by relating it to total time of inspection and time intervals before, between, and after discovery of lesions. Detection accuracy of native lesions in chest radiographs, before and after the addition of a simulated nodular lesion, was measured for ten observers. Analysis of data from this and a previous experiment showed that average perceptual accuracy of individual receiver operating characteristic curves was significantly reduced with the addition of the nodules. Plots and analyses of search time revealed that, on average, during a typical 46-second inspection of a case, simulated nodules were found at 18 seconds, native abnormalities at 25 seconds, and false positives occurred at 33 seconds. Time needed to find nodules did not depend on whether native lesions were present; time to find native lesions did not change with addition of nodules; and total search time was the same for images with one, two, or no lesions. The detection results show that the SOS effect was obtained, but that interrupting search in order to measure it also diminishes accuracy. Analysis of the time course data relates SOS to perceptual capture and strategic halting of search. PMID- 1885271 TI - Geometric quantitative coronary arteriography. A comparison of unsubtracted and dual energy-subtracted images. AB - The application of dual energy (DE) subtraction techniques to quantitative coronary arteriography (QCA) has the advantage of removing the tissue signal surrounding the vessel profile. We have compared the performance of two geometric QCA algorithms on DE-subtracted and -unsubtracted images to determine, for each, if DE subtraction is advantageous. The two algorithms under study were an edge detection algorithm and a Fourier analysis-based algorithm. For each algorithm, linear regression analysis was performed of measured cross-sectional area (CSA) versus actual CSA of coronary vessel phantoms. The edge detection algorithm was found to have improved precision (P less than .05) when applied to the DE subtracted images. The Fourier analysis algorithm, however, was not effected by the DE subtraction. Among the unsubtracted image results, the Fourier measurements were more accurate (P less than .05) than the edge detection measurements. We conclude that the benefits to edge detection QCA of DE tissue subtraction outweigh the disadvantages of increased image noise and possible misregistration artifacts. However, the Fourier algorithm is relatively insensitive to tissue signal variations. PMID- 1885272 TI - Embolization of platelets after endothelial injury to the aorta in rabbits. Assessment with 111indium-labeled platelets and angiography. AB - This study exploits the ability of a collateral arterial network to trap platelet aggregates in order to document the frequency of macroembolization in rabbits after endothelial damage. Two weeks after ligation of the right superficial femoral artery, endothelial injury was induced in the distal aorta; within 3 hours the rabbits were studied using either angiography or 111indium-labeled (111In) platelet scintigraphy. Angiography indicated visible aggregates in the thigh region in eight of 19 and arterial occlusion in three of 19 rabbits. The collateral-dependent thigh also showed more 111In-labeled platelet activity than the contralateral side (P less than .001), whether platelets were injected before or 2 hours after injury. Radioactivity in the limbs of rabbits with no injury was distributed symmetrically. Blood pool volume, assessed with technetium-99m labeled red blood cells, was the same in both thighs, and could not account for these observations. The findings indicate that platelet activation and aggregation after endothelial injury lead to microembolization much more frequently than it leads to macroaggregate formation and visible artery occlusion. PMID- 1885273 TI - In vitro ablation of normal and diseased vascular tissue by a fiber-transmitted holmium laser. AB - An in vitro study was performed to test the ablative potential of a fiber transmitted pulsed holmium laser (2.1 microns) applied to normal vascular wall, lipomatous plaques, and calcified plaques. Different fluences per pulse of 42, 80, 205, and 315 J/cm2 were used. Ablation of normal tissue and lipomatous plaques was achieved with all power settings. Effective ablation of calcified plaques, however, occurred only after a minimum fluence of 205 J/cm2, and the effect was significantly less pronounced compared to ablation of soft lesions. PMID- 1885274 TI - A comparison of iohexol and diatrizoate-meglumine in children undergoing cardiac catheterization. AB - Iohexol (Omnipaque) and meglumine and sodium diatrizoate (Renografin-76) were compared in a double-blind, randomized study for their efficacy, safety, and hemodynamic effects as angiographic contrast agents in children. Forty-four children were randomly allocated to receive either iohexol or diatrizoate as a component of their routine or emergency cardiovascular evaluation. Following age stratification, baseline physiologic parameters were not significantly different between patients receiving either iohexol or diatrizoate. After systemic ventricular injection, iohexol produced significantly less hemodynamic alteration in systemic systolic blood pressure, systemic ventricular end-diastolic pressure, and dP/dt. Less alteration in heart rate and significantly less effect on the QT interval were seen with iohexol. Image quality was comparable, although significantly more patient mobility was associated with diatrizoate-meglumine. This study shows that iohexol, a nonionic contrast medium, causes less hemodynamic disturbance than diatrizoate-meglumine in children. Therefore, its use to be preferred in these potentially high-risk patients. PMID- 1885275 TI - The effect of intravenous gadolinium on the magnetic resonance appearance of cerebrospinal fluid. AB - The authors determined whether a sufficient amount of intravenously administered gadolinium enters the cerebrospinal fluid (CSF) to visibly shorten the T1 relaxation time. Transfer of intravenously administered contrast media into the CSF has been previously documented for iodinated contrast materials; however, the change in computed tomography density is not sufficient to have a clinically useful myelographic effect. Visible shortening of the T1 of CSF on gadolinium enhanced magnetic resonance imaging of the spine may have clinical use. Twelve dogs were given gadolinium, and CSF was sampled at intervals over a 6-hour period. The T1 values of the CSF samples were quantitated and plotted against time. The average decrease in T1 was 23% at 60 minutes, which is nearly the peak effect. The increased signal intensity was visible at clinical window settings at 60 minutes. It is possible that this may be clinically useful for certain types of examinations. Importantly, this should be recognized as a normal appearance, and not necessarily a sign of pathology. PMID- 1885277 TI - Cone beam tomography of the heart using single-photon emission-computed tomography. AB - The authors evaluated cone beam single-photon emission-computed tomography (SPECT) of the heart. A new cone beam reconstruction algorithm was used to reconstruct data collected from "short scan" acquisitions (of slightly more than 180 degrees) of a detector anteriorally traversing a noncircular orbit. The less than 360 degrees acquisition was used to minimize the attenuation artifacts that result from reconstructing posterior projections of 201T1 emissions from the heart. The algorithm includes a new method for reconstructing truncated projections of background tissue activity that eliminates reconstruction ring artifacts. Phantom and patient results are presented which compare a high resolution cone beam collimator (50-cm focal length; 6.0-mm full width at half maximum [FWHM] at 10 cm) to a low-energy general purpose (LEGP) parallel hole collimator (8.2-mm FWHM at 10 cm) which is 1.33 times more sensitive. The cone beam tomographic results are free of reconstruction artifacts and show improved spatial and contrast resolution over that obtained with the LEGP parallel hole collimator. The limited angular sampling restrictions and truncation problems associated with cone beam tomography do not deter from obtaining diagnostic information. However, even though these preliminary results are encouraging, a thorough clinical study is still needed to investigate the specificity and sensitivity of cone beam tomography. PMID- 1885276 TI - Tissue relaxation enhancement after intravenous administration of (ITCB-DTPA) gadolinum conjugated albumin, an intravascular magnetic resonance imaging contrast agent. AB - Gadolinium-isothiocyanato-benzyl-diethylenetriamine pentaacetic acid (ITCB-DTPA Gd), a derivative of Gd-DTPA, was multiply conjugated to bovine serum albumin (BSA). In the synthesis of BSA-(ITCB-DTPA-Gd) conjugate, none of the five carboxylate groups of DTPA is functionalized for protein-chelate linkage. The rationale for this modification is to improve the affinity for Gd3+. We obtained a high-stability constant for the complex, comparable to unbound Gd-DTPA. Also, the complex had a T1 relaxivity as high as 30.3 seconds-1mmol-1 at 29 MHz (at 24 degrees C). At this field strength, and T1 of rat blood declined 91% after injection of 300 mg/kg of BSA-(ITCB-DTPA-Gd), corresponding to a Gd dose of 0.02 mmol/kg, while at 0.86 MHz it declined 64%. The shortening of T1 in vitro of blood, as well as spleen, lungs, and kidneys, persisted for 60 minutes. Better enhancement on post-contrast magnetic resonance images of rats was obtained at 1.0 T than at 0.04 T. Tissues with rich vascularization and large venous structures were well displayed at the higher field. PMID- 1885278 TI - Practice policies. Rationale, methods of development, and implications for radiologic practice. PMID- 1885279 TI - Disclosure to patients. How far must it go? PMID- 1885280 TI - Lumbar disk herniation and canal stenosis value of intraoperative sonography in diagnosis and surgical management. PMID- 1885281 TI - The decline of deference: the political context of risk communication. PMID- 1885282 TI - Chief complaint. PMID- 1885283 TI - "... ma non piu bello". PMID- 1885284 TI - Epidemiology of respiratory syncytial virus infection among infants over three winter seasons. AB - A study involving respiratory syncytial virus was carried out on infants and young children hospitalised with acute respiratory tract infection over the period December 1987 to March 1990. During peak periods of RS virus activity 420 naso-pharyngeal aspirates were submitted to the Virus Reference Laboratory, Department of Medical Microbiology, U.C.D., mostly from the Dublin region. Using immunofluorescence, enzyme linked immunosorbent assay and cell culture techniques 206 samples (49%) were identified as positive for RS virus. Over the period of study RS virus seasonal activity was confined to the winter months October to March with peaks of activity occurring during March 1988, December 1988 and January 1990. Bronchiolitis was the most common clinical manifestation of infection accounting for 48% of the total number of positive results. Eighty two point five per cent of positive detections were reported from infants less than or equal to 6 months old and particularly from infants in the 1-2 month old age group. More males than females were found to be affected by RS virus infection. PMID- 1885285 TI - Control of growth in preimplantation embryos. AB - I would like to thank the President and the Selection Committee of the Academy for the honour of an invitation to present the 1990 Conway Review Lecture. The subject of the topic is the Control of Growth in Preimplantation Embryos. PMID- 1885286 TI - Management of reflux oesophagitis: role of weight loss and cimetidine. AB - A double blind clinical trial was performed to evaluate the effect of weight loss and cimetidine in the treatment of reflux oesophagitis. Thirty-two patients were evaluated by endoscopy, L.O.S.P. determination, oesophageal scintigraphy and ambulatory 24 hour oesophageal pH monitoring. Patients were randomly allocated into treatment using a regimen of placebo/weight loss or cimetidine/weight loss. Assessments were repeated after 8-12 weeks. A similar weight loss and improvement in symptoms and endoscopy appearances was seen in both groups. In contrast there was no significant change in frequency or duration of reflux on 24-hour pH monitoring or oesophageal scintigraphy or L.O.S.P. We conclude that weight loss may have an important role in the treatment of reflux oesophagitis and should be recommended to patients as an early therapeutic intervention. Cimetidine did not confer any additional benefit to that obtained from weight loss alone. PMID- 1885287 TI - Abdominal aortic aneurysms: the importance of elective repair. AB - Repair of abdominal aortic aneurysms (AAA) is being performed with a progressively lower mortality and morbidity. We reviewed 111 patients who underwent repair of their AAA. Sixty-two were electively repaired and 49 had emergency surgery. Eight patients had cocomitant non-vascular procedures carried out. Operative mortality was 3.2% and 49% for elective and emergency cases respectively. Postoperative complications occurred in 40% of elective cases and 72% of emergency cases, respiratory complications being the most common, occurring in 25% and 40% of elective and emergency cases respectively. Subsequent graft complications occurred in six patients, five following emergency surgery. PMID- 1885288 TI - The Monk Hard-Top prosthesis for displaced intracapsular fractures of the femoral neck. AB - The Monk Hard-Top prosthesis was inserted without operative mortality in 85 patients, with an average age of 81 years, presenting with Intracapsular Fracture of the Femoral Neck, Garden grade 3 or 4. At review, 60% of the patients walked unaided, without pain. Only 6% of those reviewed had a poor functional outcome. Fifty-three per cent of the patients returned to their previous environment and 47% had died 6 months postoperatively. The prosthesis is more difficult to dislocate, once inserted properly, than either a Thompson Hemiarthroplasty or a Primary Total Hip replacement. It is less likely to sustain Component Disassembly than other types of bipolar hemiarthroplasty. The Monk Hard Top Prosthesis is recommended for the treatment of Garden grade 3 or 4 Intracapsular Fractures of the Femoral Neck in elderly people. PMID- 1885289 TI - It looks like agromegaly but it is not. PMID- 1885290 TI - Setting health care priorities. Oregon's next steps. PMID- 1885291 TI - The Oregon priority-setting exercise: quality of life and public policy. PMID- 1885292 TI - At law. Ethics committees: from ethical comfort to ethical cover. PMID- 1885293 TI - Maternal rights, fetal harms. PMID- 1885294 TI - Recognizing suffering. PMID- 1885296 TI - In the clinical mode. PMID- 1885295 TI - Teaching ethics: right to refuse? PMID- 1885297 TI - Knowing when to stop: the limits of medicine. PMID- 1885298 TI - The molested. PMID- 1885299 TI - Gestational cadmium exposure and brain development: a biochemical study. AB - The neurochemical effects of maternally administered cadmium (50 ppm through drinking water from 0 day of pregnancy) on the whole brain of offsprings exposed during gestation were studied in 7, 14 and 21 days old rats. The developmental pattern of body weight, protein, DNA and RNA contents in brain were not affected in Cd exposed pups of any age group. Brain weights were significantly reduced in exposed pups of postnatal age of 7 and 14 days but were comparable to controls in 21 days old pups. The content of Cd increased significantly in the brain of gestationally exposed pups of 7 days and remained almost stationary throughout the experimental period. The activity of Acetylcholinesterase, Na+, K(+)-ATPase, CNPase, 5'-Nucleotidase in the brain increased significantly from 7 to 21 days of age in control animals. In experimental pups, the activity of most of the enzymes was almost comparable to controls at 7 days of age except succinate dehydrogenase, which was significantly inhibited at 7, 14 and 21 days compared to controls. The activity of other enzymes was also significantly inhibited in the brain of experimental pups compared to controls of 21 days of age indicating marked retardation in the development of these enzymes. However, these changes had no correlation with the accumulation of Cd in the brain. These studies indicate that in utero exposure to Cd may retard the development of certain neurochemicals which may have long term implications on the brain functions. PMID- 1885300 TI - Peritoneal mesothelioma--how a good occupational case history can best be used. PMID- 1885301 TI - Cadmium intake and age in beta 2-microglobulinuria: categorical data analysis in epidemiology. PMID- 1885302 TI - Dogs from southwest Asia may pose a zoonotic disease threat. PMID- 1885303 TI - Comments on stress and burnout article. PMID- 1885304 TI - Amputation of the tail of a horse as the basis for a malpractice suit. PMID- 1885305 TI - Teaching veterinary students: thinking in different terms. PMID- 1885306 TI - From Brooklyn to barnyards. PMID- 1885307 TI - The happy camper. PMID- 1885308 TI - Direct costs of pseudorabies in a population of infected farrow-to-finish swine herds. PMID- 1885309 TI - Preoperative prognostic indicators in cattle with abomasal volvulus. AB - A prospective study evaluating preoperative prognostic indicators in 80 cattle with abomasal volvulus was done. Surgical correction of the abomasal volvulus was performed in all animals. After surgery, cattle were categorized into 3 groups: productive (acceptable milk production or appetite, n = 59), salvaged (poor milk production or appetite, n = 10), and nonsurvivors (n = 11). Mean values for study variables did not differ significantly between salvaged and nonsurvivor groups. Cattle in these 2 groups were combined to form a nonproductive group, which was compared with the productive group. Productive cattle had a significantly lower preoperative heart rate than nonproductive cattle, were less dehydrated, had lower serum alkaline phosphatase (ALP) activity and serum creatinine concentration, more frequent rumen contractions, higher serum Na+ and Cl- concentrations, and had been inappetent for a shorter period. Significant differences were not detected in blood pH, base excess, anion gap, PCV, and serum K+ concentrations between the 2 groups. Feces from nonproductive cattle tended to be reduced in volume and were significantly darker. A number of preoperative prognostic indices were evaluated by calculating the sensitivity, specificity, and positive predictive value (+PV) of each variable and by using logistic regression. Positive predictive values were generally higher in identifying productive cattle than nonproductive cattle.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1885310 TI - Clinical relevance of radiographic findings in proximal sesamoid bones of two year-old standardbreds in their first year of race training. AB - Radiographs of all 4 fetlocks of 71 Standardbred racehorses were obtained at 3 month intervals for 1 year. Radiographic findings in the abaxial surface of the proximal sesamoid bones were classified into 3 types according to the severity of lesions, and correlation was made with clinical findings at time of examination. Type-1 lesions (1 or 2 linear defects less than or equal to 1 mm wide) were detected in 55% of horses at the start of training; clinical signs of disease were not manifested, and lesions did not become clinically relevant. Type-2 lesions (3 or more linear defects less than or equal to 1 mm wide) were detected in horses not manifesting clinical signs of disease, and were more frequently observed after 3 months of training. However, 66% of horses affected with diseases of the suspensory apparatus, including superficial flexor tendinitis and suspensory desmitis, also manifested this type of lesion. When lameness was observed, it was associated with the soft tissue problem, and the sesamoid bone changes were considered secondary. Type-3 lesions (wide, abnormally shaped linear defects) were detected in 7 horses at the start of the study; lesions remained in horses throughout the study and were consistently associated with lameness during training. Type-3 lesions were considered clinically relevant and indicative of primary sesamoiditis. PMID- 1885311 TI - Intervertebral disk prolapse and diskospondylitis in a horse. AB - Intervertebral disk prolapse was diagnosed in a mature horse with clinical signs of caudal ataxia. Radiography and myelography demonstrated a collapsed intervertebral space and loss of the dorsal and ventral dye columns. Results of CSF analysis were normal, as were a CBC and serum biochemical profile. High CSF WBC count and high CSF creatine kinase activity were noticed following acute neurologic deterioration. While common in certain breeds of dogs, intervertebral disk prolapse is rarely reported in horses. It should be considered in the differential diagnosis of horses with caudal ataxia. PMID- 1885312 TI - Resection of a cervical tracheal bronchus in a foal. AB - A 3-day-old Thoroughbred foal developed a large, air-distended, midcervical swelling that was diagnosed as a congenital tracheal bronchus with associated ectopic lung tissue. Clinical signs consisted of a compressible air-filled sac that enveloped the trachea. The nature and extent of the defect were evaluated endoscopically and radiographically. Surgical resection of the bronchus and associated air-filled sac resulted in a functionally and cosmetically acceptable outcome. PMID- 1885313 TI - Sinus mucocele secondary to craniofacial trauma in a dog. AB - A sinsus mucocele formed in the frontal sinus of a dog secondary to obstruction of the nasofrontal opening. The dog was successfully treated by surgical enlargement of the nasofrontal opening, curettage of the sinus epithelium, and placement of a fat graft and drain in the sinus. Although mucocele formation is uncommon in animals, it should be considered as a differential diagnosis for masses of the sinonasal area. Characteristic radiographic and cytologic findings should alert the clinician to this diagnosis, and along with aggressive treatment, should shorten the diagnostic and treatment delay experienced by the dog in this report. PMID- 1885314 TI - Radiographic findings in young llamas with forelimb valgus deformities: 28 cases (1980-1988). AB - Twenty-eight llamas with a mean age of 6.2 months had bilateral forelimb valgus deformities. The range of valgus deformity, as measured on a craniocaudal radiographic view, was 6 to 25 degrees, with a similar degree of deviation in each limb. Morphologic abnormalities in the distal portion of the radius and ulna were more prominent in the ulna and included metaphyseal and epiphyseal flaring, physeal ectasia, and metaphyseal sclerosis. Distal radial epiphyseal ectasia, and metaphyseal sclerosis. Distal radial epiphyseal wedging was believed to be secondary to the ulnar deformity. Radial bowing with lateral and caudal concavity and unequal cortical thickness was evident. Epiphyseal and metaphyseal flaring with physeal ectasia was noticed in the distal portion of the third and fourth metacarpal bones. Carpal bones were unaffected. PMID- 1885315 TI - Comparison between diagnostic ultrasonography and radiography in the evaluation of horses and cattle with thoracic disease: 56 cases (1984-1985). AB - The results of radiography and ultrasonography were compared on 56 horses and cows with lower respiratory tract disease. Ultrasonography was more sensitive than radiography for the detection of small pleural effusions and consolidations in large animals. The side of the thorax affected and the character of the pleural fluid and lung in large animals with pleural effusion can be evaluated ultrasonographically. The periphery of the lung must be affected to characterize pulmonary lesions ultrasonographically. Radiography is the best technique to characterize lesions deep within the lung when the periphery of the lung is normal. PMID- 1885316 TI - Trends in veterinarians' professional incomes, 1980 to 1989. PMID- 1885317 TI - What is your diagnosis? Circumscribed circular mineralized and soft tissue mass filling the tracheal lumen ventral to C3. PMID- 1885318 TI - Use of large-animal pharmaceuticals in small animals. PMID- 1885319 TI - Cholinesterase activity in domestic animals as a potential biomonitor for nerve agent and other organophosphate exposure. PMID- 1885320 TI - Disturbed about research on electroimmobilizer. PMID- 1885321 TI - Abuse of anabolic steroids. PMID- 1885322 TI - What is your diagnosis? Diffuse pulmonary interstitial density, splenomegaly, and generalized lymphadenopathy. PMID- 1885323 TI - What is your diagnosis? Hematoma extending from the pelvic inlet around the kidneys. PMID- 1885324 TI - Ties "puppy mills" letter to animal rights movement. PMID- 1885325 TI - Drug use discussed at milk shippers' conference. PMID- 1885326 TI - History of veterinary medicine in the Food and Drug Administration. PMID- 1885327 TI - Leaving the shadows of Yale for the majestic mountains of Colorado. PMID- 1885328 TI - ECG of the month. PMID- 1885329 TI - Veterinary medical informatics. PMID- 1885330 TI - Electrified milking parlors still a current issue in the courts. PMID- 1885331 TI - Comparison of culture, peroxidase-antiperoxidase reaction, and serum latex agglutination methods for diagnosis of chlamydiosis in pet birds. AB - Comparison was made among results of cloacal specimen culture, and cloacal swab specimen (cytologic) peroxidase-antiperoxidase (PAP), serum latex agglutination (LA), and tissue PAP assays for diagnosis of chlamydiosis in 144 birds. Swab specimen PAP findings correlated poorly with LA results and failed to predict the LA test result in any bird. Only 1 cloacal swab specimen was regarded as PAP positive and was from the cloaca of a bird from which chlamydiae were isolated in culture. The sensitivity of swab specimen PAP, compared with culture results, was 33%, whereas specificity was 94%. In this study, swab specimen PAP was a less sensitive test, compared with culture, than was reported in a previous study. The sensitivity of LA in identifying birds that were cloacal culture-positive was poor; true-positive results were not detected, compared with culture results. The specificity of the LA method was 93%, compared with culture results. Results of the tissue PAP method correlated with culture results in the 3 birds for which both tests were performed. PMID- 1885332 TI - Greater participation by veterinarians in the reproductive management of dairy cattle. AB - A program involving greater veterinary participation in detection of estrus and artificial insemination of cattle was evaluated in a 700-cow dairy herd from January 1987 through August 1988. Previous reproductive performance was below normal. First-service pregnancy rate from artificial insemination was 42%, and mean number of nonpregnant days for the cows was 120. Between postpartum days 55 and 62, all cows with functional corpus luteum assessed by rectal palpation were administered prostaglandin each Monday morning. Return visits were made to the herd each Thursday and Friday to observe cows and to inseminate those in estrus. On the other 5 days of the week, the owner or his employees inseminated all cows in estrus. The first-service pregnancy rate for 842 cows observed in estrus and inseminated by the veterinarian was 59%. The pregnancy rate for cows inseminated by the owner and his employees increased from 42% to 50%. The mean number of nonpregnant days for all 700 cows decreased from 120 to 98 days, resulting in approximately $46,000 of increased income for the dairyman or approximately a 4 to 1 return on investment in veterinary service. Results indicate that veterinarians could improve herd reproductive performance and solve chronic herd breeding problems by more actively participating with their clients in estrus detection and artificial insemination programs in cattle. The program allows practicing veterinarians an opportunity to observe cows for estrous behavior, establish their own pregnancy rate data, demonstrate to owners the importance of observing primary signs of estrus, and teach expert artificial insemination techniques. PMID- 1885333 TI - Diabetes mellitus induced in a dog after administration of corticosteroids and methylprednisolone pulse therapy. AB - An 8-year-old ovariohysterectomized Chow Chow was referred because of dermatologic lesions diagnosed as pemphigus foliaceus. Intolerance to orally administered corticosteroids necessitated the use of methylprednisolone pulse therapy. One week after treatment, diabetes mellitus was diagnosed on the basis of blood and urine test results. For 3 years after treatment, the dog has remained a well-regulated diabetic. Complete remission of pemphigus foliaceus is maintained by alternate-day, orally administered prednisone (0.5 mg/kg of body weight). PMID- 1885334 TI - Hyperthyroidism associated with a thyroid adenoma in a dog. AB - Hyperthyroidism associated with thyroid adenoma was diagnosed in a dog. Typical clinical signs of hyperthyroidism were resolved with surgical excision of the adenoma. Hyperthyroidism in dogs usually is associated with thyroid carcinoma, which has a poor prognosis. This case emphasizes the importance of obtaining a histologic diagnosis of thyroid tumors in hyperthyroid dogs before giving a prognosis. PMID- 1885335 TI - Applications of a semitendinosus muscle flap in two dogs. AB - The proximal half of the semitendinosus muscle can be used as a versatile vascularized local transposition flap to reconstruct anatomic faults in the adjacent perineum in dogs. The flap is easy to dissect, and the arc of rotation is considerably beyond the midline. The location, size, and direction of the major vascular pedicle from the caudal gluteal artery is conducive to dependable flap perfusion. PMID- 1885336 TI - Esophageal hiatal hernia and megaesophagus complicating tetanus in two dogs. AB - Two dogs with tetanus developed transient megaesophagus and hiatal hernia associated with gastroesophageal reflux and regurgitation. The megaesophagus and hiatal hernia were diagnosed radiographically and resolved with resolution of the tetanus. These 2 cases, plus previously reported cases, indicate that tetanus can cause megaesophagus and esophageal dysfunction. Therefore, thoracic radiography should be included as part of the diagnostic evaluation of dogs suspected of having tetanus. PMID- 1885337 TI - Squamous cell carcinoma of the hoof wall in a stallion. AB - Squamous cell carcinoma of the hoof wall, with resultant invasion of the right hind distal phalanx, was identified in a 15-year-old Thoroughbred stallion. The clinical features included a chronic grade 2/5 right hind limb lameness and a sessile dorsal hoof wall mass that was not sensitive to palpation. Radiography revealed a well-circumscribed circular lucency within the distal phalanx, beneath the clinically noticed hoof wall mass. These features were considered to be characteristic of a hoof wall keratoma. Surgical intervention was done 10 months later. The histologic diagnosis at the time of surgery was squamous cell carcinoma. Eight months after surgery, progressive tumor invasion of the distal phalanx resulted in a pathologic articular fracture. This case highlights the need for accurate histologic diagnosis of equine hoof wall masses to differentiate between benign and malignant conditions. PMID- 1885338 TI - Clinical and laboratory findings in small companion animals with lead poisoning: 347 cases (1977-1986). AB - Three hundred forty-seven cases of lead poisoning in small companion animals were reviewed. The yearly prevalence and overall incidence rates were examined for the 10 years before and after enactment of strict federal regulations pertaining to lead content in paint products. Biographical data, clinical signs, and laboratory results were analyzed for the 6 types of affected animals (ie, dogs, cats, birds, rabbits, a chinchilla, and a raccoon). Clinical and laboratory findings of these animals were then compared with findings of other studies of lead intoxication. PMID- 1885339 TI - The experiences of women who face abortions. AB - Seventy-two Israeli women who were about to have abortions were interviewed. These women experienced intense emotions of sadness, ambivalence, confusion, and fear. To help them deal with this crisis, the women expressed a need for a professional counselor who provides information such as where to go, how to get money for the abortion, and how the operation is performed. The women also wished that the professional counselor would support them emotionally throughout the pregnancy experience and the abortion procedure. PMID- 1885340 TI - Pain and distress during abortion. AB - Although there has been recent emphasis on the long-term effects of abortion on women, the distressing aspects of the procedure itself are seldom addressed. The pain and distress experienced by 35 women undergoing first-trimester abortion were addressed. The quality and intensity of pain were measured using the McGill Pain Questionnaire (MPQ) and a pain intensity visual analog scale (VAS). Distress measures included a VAS, state anxiety, observation of behavior, and observer rated distress. The women reported elevated levels of state anxiety before the abortion and pain and distress during the procedure. The pattern of verbal descriptors on the MPQ was comparable to previously reported descriptors of abortion, labor, and menstrual pain. The MPQ dimension scores did not differ by type of anesthesia received. Findings indicate that first-trimester abortion is a painful and distressing medical procedure and support the use of the MPQ as a measure of the character and intensity of the pain experienced. PMID- 1885341 TI - Retrospective assessment of premenstrual changes in Icelandic women. AB - The purpose of this study was to increase our knowledge of the condition of Icelandic women aged 29 to 40 years during the premenstrual phase of the menstrual cycle. Premenstrual symptoms were measured by a retrospective instrument adapted from Halbreich and colleagues' Premenstrual Assessment Form. Our findings showed that Icelandic women experience premenstrual changes as do their peers in other countries. The most common symptoms were bloating, mood swings, irritability, abdominal discomfort-pain, and intolerance-impatience. Women who were symptomatic in the week before menses tended to manifest more symptoms at other times as well. In general, women responded to their symptoms by taking some time to relax, take pain medication, or seek support. Women experiencing more severe symptoms were more likely to seek support from a partner, relative, or friend. More than 40% of the sample reported that they perceived the symptoms as having negative effects on their relationships with their partners and children, and those experiencing more severe symptoms were more likely to report these perceptions. PMID- 1885342 TI - Infertile couples' perceptions of infertility support-group participation. AB - Although nursing authors recommend that infertile clients be referred to infertility support groups, no study has identified the benefits of participation in such groups. This exploratory descriptive study investigated the benefits of infertility support-group participation as perceived by 16 men and 22 women. A questionnaire developed and used for the study consisted of open- and closed ended questions and included a 42-item Infertility Support Group Perception Scale for which an internal consistency reliability of .91 was established. Most important, least important, anticipated, and unanticipated benefits perceived by the total group, male and female subgroups, and participation subgroups were explored. We found that significantly fewer men than women initially wanted to join the group (p less than .01), but both men and women perceived similar amounts of benefit. Anticipated and unanticipated benefits differed between men and women. Length of membership and frequency of attendance were both positively correlated with amount of benefits perceived. PMID- 1885343 TI - Walking the line between feminism and infertility: implications for nursing, medicine, and patient care. AB - Traditionally infertility has been viewed as a medical condition and has been managed within the medical model of diagnosis, treatment, and cure. The prevalence of infertility has been medically explained by women's sexual promiscuity, pursuit of professional career advancement, and psychological immaturity. Although authors have recently recognized an equitable proportion of infertility problems attributable to male factors, the vast majority of infertility testing and treatment procedures remain directed toward women. Reproductive technologies and their potential for perpetual treatment create a scenario of vulnerability for the infertile woman, which demands the attention of care providers who advocate feminist values of health. In this article, we present a historical overview of infertility and offer a feminist perspective for providing physical and emotional health care to infertile women. Strategies for integrating feminist perspectives of health into infertility programs are discussed. PMID- 1885344 TI - Recovery from childbirth: looking back 6 months after delivery. AB - Women's perceptions of their recovery from childbirth were investigated by open ended interviews of 96 mothers of health, full-term infants 6 months after delivery. Data included factors affecting physical, mental, and emotional recovery; sources of help and hindrance; ideas of what each women would do differently after the delivery of another child; and overall evaluation of how the months after delivery compared with expectations. Content analysis of the data revealed that 25% of the women did not feel physically recovered from childbirth at 6 months postpartum. Husbands and other family members were major sources of help. Prolonged labor and cesarean delivery were the major hindrances to recovery. More household and child-care help was desired after delivery of another child. Almost half of the women found the first 6 months after delivery more difficult than anticipated. The findings suggest that pregnant women need more information about lifestyle adjustments after childbirth. PMID- 1885346 TI - Yearling adjustments for pelvic area of test station bulls. AB - Yearling bulls (n = 3,071) located at 18 stations in Missouri, Nebraska, Virginia, and Wisconsin were measured for pelvic area, in addition to standard performance traits. Linear adjustments for age and weight were determined using covariate regression analyses. Only bulls that were 300 to 452 d of age, 325 to 640 kg, and were in consignments offering more than nine bulls per breed were included in the analyses. Because the subsets of Angus, Polled Hereford, and Simmental bulls had large numbers of observations (817, 271, and 449, respectively), individual adjustment coefficients were determined for each breed. Angus, Polled Hereford, and Simmental bulls had pelvic area adjustment regressions on age of .20, .32, and .20 cm2/d, respectively, and regressions on body weight of .15, .22, and .18 cm2/kg, respectively. Homogeneous linear responses of all breeds (11 breeds including Angus, Polled Hereford, and Simmental) were combined to form all-breed coefficients for age and weight adjustments, which were .21 cm2/d and .15 cm2/kg, respectively. Weight or age adjustments can be used to compare contemporaries for relative pelvic area differences, but both should not be used on the same bull. Although many factors contribute to dystocia, high priority should be given to identifying sires of replacement heifers of low to moderate birth weight genotype and above average pelvic area genotype. PMID- 1885345 TI - Computer hazards: real or imaginary? AB - Extensive use of video display terminals (VDTs) and reports of suspected adverse health effects attributed to their operation have increased operator concern and interest. Information to assist supervisors and health personnel in responding to health-related questions and in evaluating the workplace for dangers concerning VDTs is provided. PMID- 1885347 TI - Recombinant porcine somatotropin alters performance and carcass characteristics of heavyweight swine and swine fed alternative feedstuffs. AB - The efficacy of recombinantly derived porcine somatotropin (rpST) in improving the performance and carcass characteristics of heavyweight finishing pigs was determined. In Study 1, 36 pigs were killed for determination of initial carcass composition at 102 kg, and 36 pigs each were given 0, 1.5, 3, 6, or 9 mg of rpST/d from 102 to 136 kg live weight. Corn-soybean meal diets fed contained 19.8% CP and greater than 1% lysine. Study 2 tested the effects of 3 mg/d on pigs for 4 wk from 84 kg BW fed a corn-soybean meal or a triticale-barley-peas diet. Performance variables (ADG, average daily feed intake [ADFI], and feed efficiency [FE]) were measured weekly. Treatment with rpST increased (P less than .01) ADG and FE and decreased (P less than .01) ADFI in both studies. In Study 1, leaf fat, backfat thickness, belly thickness, and carcass fat were all decreased (P less than .01) linearly by rpST. Loin eye area (LEA), total trimmed lean, and total protein content were increased quadratically (P less than .01). At the 3-mg dose, ADFI, ADG, and FE were 87, 130, and 137% of control, and LEA, backfat, total protein gain, and total fat gain were 107, 80, 136, and 52% of control. Loin eye area was not increased (P greater than .05) in the pigs in Study 2; however, backfat thickness was reduced 16% by rpST (P less than .01). The effects of rpST were the same on both dietary regimens (P greater than .05). These studies demonstrate the effectiveness of rpST in increasing ADG and carcass leanness and improving FE in heavyweight pigs and in pigs fed alternative feedstuffs. PMID- 1885348 TI - Escape protein for beef cows: I. Source and level in corn plant diets. AB - Two gestating cow winter grazing trials and two lactating cow drylot trials were conducted to evaluate the use of a slowly degraded protein source in corn plant diets for mature beef cows. Gestating beef cows grazing cornstalks were supplemented with .86 kg/(cow.d) of a 20% crude protein equivalent (CPE) pellet (DM basis). In Trial 1 cows fed diets containing 80% dehydrated alfalfa meal (high DEHY) gained more weight (P less than .05) than those fed diets containing 40% dehydrated alfalfa meal (low DEHY) or urea but not more than the cows fed soybean meal (SBM); however, no differences among treatments were observed in Trial 2. Four lactation diets composed of ground corncobs and corn silage were supplemented with either urea, SBM, or two levels of dehydrated alfalfa meal (DEHY) as N sources. The same amount of supplemental N was fed in both trials, consisting of .31 kg of natural protein for the SBM and low DEHY treatments or .42 kg for high DEHY. Ammoniated corncobs replaced 35% of the ground corncobs in Trial 4. Diets were calculated to contain (DM basis) 55% TDN and 9% CPE in Trial 3 and 11% CPE in Trial 4. In Trial 3, lactating cows supplemented with DEHY gained more weight (P less than .10) than those fed the urea supplement but not more than those fed SBM. Gains by cows fed the urea- and SBM-supplemented diets were not different (P greater than .10). Cow weight gains in Trial 4 were not affected by type of protein supplementation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1885349 TI - Escape protein for beef cows: II. Source and level in ammoniated wheat straw-corn silage diets. AB - Two experiments, using Angus x Hereford spring-calving beef cows in mid- or late lactation nursing Simmental-sired calves, were conducted to evaluate the relative value of a corn gluten meal-blood meal mixture (CGM-BM; 50% of supplemental protein from each source). In Exp. 1 (78 d), cows in late lactation were assigned to one of three treatments: control at 8.2% CP (C), soybean meal at 10.4% CP (SBM), or CGM-BM at 10.3% CP. Diets were calculated to be isocaloric at 55% TDN. In Exp. 2 (65 d), cows in mid-lactation were assigned to four treatments: urea, SBM, low CGM-BM (LM), and high CGM-BM (HM). Diets in Exp. 2 were isonitrogenous (9.5% CP) and isocaloric (55% TDN). Diets in both experiments were based on ammoniated wheat straw and corn silage. Weight gains of cows and cow-calf pairs were greater (P less than .06) when protein was supplemented in Exp. 1. Gains were lower for cows fed urea (P less than .03) in Exp. 2 but were similar when cows were supplemented with SBM vs either the low or the high level of CGM-BM. Performance of calves did not differ among dietary treatments. PMID- 1885350 TI - Effect of group thawing on post-thaw viability of bovine spermatozoa packaged in .5-milliliter French straws. AB - The objective of this study was to determine the effects of thawing groups of 2, 5, 10, 15, or 20 .5-ml French straws on post-thaw spermatozoal viability. Thermostatically controlled and nonthermostatically controlled thawing baths were compared. Using a split-plot design, semen from 10 bulls was extended in egg yolk citrate, frozen, and then thawed (in the respective groups) at 36 degrees C in two types of thawing baths. Motility and percentage of intact acrosomes were determined immediately after thawing (0 h) and again after 4 h of incubation at the respective temperature of each thawing bath. Neither percentage of intact acrosomes nor motility was influenced by the number of straws thawed at 0 h (P greater than .05). Thawing bath had no effect (P greater than .05) on motility or percentage of intact acrosomes at 0 h. Bull variation was significant in both the 0- and 4-h evaluations. After 4 h of incubation, there was a significant (P less than .05) straw number x thawing bath interaction. When 15 or 20 straws were thawed in the thermostatically controlled bath there was a reduction (P less than .05) in motility and percentage of intact acrosomes. However, in the nonthermostatically controlled bath there was no reduction in motility and percentage of intact acrosomes as the size of straw group increased. Our results indicate that, when using a nonthermostatically controlled thawing bath, semen packaged in .5-ml straws can be thawed in groups of 20 without an effect on post thaw sperm viability. PMID- 1885351 TI - A Markovian decision model for beef cattle replacement that considers spring and fall calving. AB - In certain production environments, beef cows are mated during a breeding season that starts in early summer. Cows found not to be pregnant at the end of the breeding season could either be culled or retained and remated the following summer. Alternatively, nonpregnant cows could be mated in the winter. This option would result in having both a spring and a fall calving herd. The purpose of our study was to determine the optimal replacement policy (maximizing long-run average net returns) for a specific production environment by determining for each age of cow, reproductive status (nonpregnant or pregnant), and season of pregnancy checking (spring or fall) whether the cow should be retained to the next breeding season (summer or winter) or be replaced by a pregnant heifer. The problem was formulated as a Markovian decision process and the optimal policy was found by linear programming. The optimal policy was one in which nonpregnant cows were always culled and replaced by heifers in the summer breeding herd, resulting in spring calving only. PMID- 1885352 TI - Evaluation of reproductive traits in Bos taurus and Bos indicus crossbred heifers: effects of postweaning energy manipulation. AB - Reproductive traits were evaluated in Bos taurus and Bos indicus crossbred heifers that were fed different diets during the postweaning period. The study was designed in a 2 x 2 x 2 factorial arrangement of treatments. Angus x Hereford (AH; n = 148) and Brahman x Hereford (BH; n = 148) heifers were sorted after weaning by body weight into light (LW) and heavy (HW) weight blocks. Heifers in each weight block were assigned to diets calculated to reach a target weight of 55% (LE) or 65% (HE) of their projected mature weights by the start of the breeding season. Puberty was determined after a 160-d observation period and characterized by the following criteria: 1) behavioral estrus, 2) presence of a palpable corpus luteum (d 6 to 10; estrus = d 0), and 3) rise in serum progesterone above 1 ng/ml (d 6 to 10). A higher (P = .01) proportion of AH heifers than of BH heifers reached puberty by the breeding season (93% vs 67%). Interactions of breed x weight block and energy level x weight block also contributed to this difference. Weight at puberty was heavier (P = .001) among HE than among LE heifers and greater for heifers in HW than for those in LW blocks (P = .02). Differences in prebreeding weight, body condition, average daily gain, hip height, and pelvic area were influenced selectively by breed, energy level, or weight block. Pregnancy rates were higher (P = .01) among AH than among BH heifers. Incidence and severity of dystocia was influenced by the breed x energy level interaction (P = .01). Brahman x Hereford heifers had less (P = .01) dystocia than AH heifers, HE heifers had less (P less than .02) dystocia than LE heifers, and HE-AH heifers had less (P less than .01) dystocia than LE-AH contemporaries. Subsequent duration of the postpartum interval to estrus was shorter (P = .002) among AH than among BH females. Pregnancy rates at the end of the 2nd yr were higher (P = .02) among LW than among HW females and weights were heavier (P = .001) at weaning among calves weaned from BH dams. PMID- 1885353 TI - Genetic and environmental growth trait parameter estimates for Brahman and Brahman-derivative cattle. AB - Beefmaster, Brahman, Brangus, and Santa Gertrudis field data records were used to determine genetic and environmental parameter estimates using a multiple-trait, pseudo-expectation approach. Adjusted birth weight, 205-d weight, and postweaning gain records were analyzed for each breed. Also, Brangus weaning sheath and navel scores were both analyzed using a single-trait, pseudo-expectation method to determine genetic parameter estimates. Additive birth weight heritability (h2A) estimates ranged from .22 to .37 and maternal birth weight heritability (h2M) estimates ranged from .12 to .55. Estimates for 205-d weight h2A for the four breeds varied from .21 to .25, and 205-d weight h2M estimates ranged from .15 to .21. Postweaning gain h2A estimates ranged from .16 to .56. The genetic correlation between direct and maternal portions of birth weight was negative for all breeds. This was also true for the genetic correlation between direct and maternal portions of 205-d weight, except in Brahman cattle, for which it was .15. The genetic correlation between additive portions of birth weight and 205-d weight was large and positive in all breeds. A moderately positive correlation between 205-d weight and postweaning gain was found for all breeds except Santa Gertrudis, whereas the environmental correlation between these two traits was a small to moderately negative estimate in all breeds. Brangus weaning sheath and navel score heritabilities indicated that genetic change for the size and shape of the sheath and navel area is possible. PMID- 1885354 TI - Evaluation of purebred and crossbred rabbits for carcass merit. AB - Two hundred twenty-six fryers representing four breed types, New Zealand White (NZW) and Californian (CAL) purebreds, CAL x NZW (CxN), and Flemish Giant (FG) terminal crossbreds (the latter group including FG x CAL, FG x CHA [CHA = Champagne D'Argent], and 1/2FG x 1/4CAL x 1/4CHA), were appraised for carcass merit. Evaluation criteria included the following: preslaughter and carcass weights; pelt, visceral, giblet, abdominal fat, and dressing percentages; percentages of carcass in loin, forequarter, and hindquarter primal cuts; and weight of lean in loin and ratio of lean to bone weight in loin cut. The least squares model consisted of breed type (B), season of birth (S), and gender (G) as fixed effects, B x G and S x G interactions, litter within B and S as a random variable, and random residual. Breed type influenced (P less than .10) all traits except giblet and forequarter cut percentages. Season of birth significantly influenced all all traits except percentage of loin cut. Gender of rabbit affected (P less than .05) only the percentage of forequarter cut. A B x G interaction was observed (P less than .05) for pelt and visceral percentages. The NZW control purebreds were generally inferior (P less than .05) to the three other breed types for carcass yield and cutability traits. Purebreds were lighter for preslaughter, carcass, and loin lean cut weights and lower for loin lean-to bone ratio than were CxN crossbreds (P less than .05). The FG crossbreds had heavier preslaughter and carcass weights and a lower abdominal fat percentage (P less than .01) than NZW, CAL and CxN. Results of this study provide corroborative evidence in support of terminal crossbreeding using CAL sires with NZW dams and FG purebred or crossbred sires with CAL and CHA purebred or crossbred dams to improve carcass merit. PMID- 1885355 TI - Life span of beef-type Bos taurus and Bos indicus x Bos taurus females in a dry, temperate climate. AB - Females representing Hereford, Red Poll, F1 Hereford x Red Poll, F1 Red Poll x Hereford, F1 Angus x Hereford, F1 Angus x Charolais, F1 Brahman x Hereford, and F1 Brahman x Angus breed types were evaluated from birth until 10 yr of age. Of 308 females born alive, 35.7% died or were culled because of injury, serious illness, or reproductive failure. Breed types differed (P less than .01) in total number of mating seasons per cow and total number of progeny born and weaned. Values for lifetime total number of calves weaned were as follows: Hereford, 4.54; Red Poll, 5.45; Hereford x Red Poll, 4.45; Red Poll x Hereford, 5.49; Angus x Hereford, 5.98; Angus x Charolais, 5.57; Brahman x Hereford, 6.96; and Brahman x Angus, 6.22. Brahman crosses (P less than .01) and Angus x Charolais (P less than .10) exceeded Hereford dams in lifetime total number of calves weaned but did not differ from Angus x Herefords. Analysis of the Hereford-Red Poll diallel showed no evidence of heterosis in life span traits. Results indicate that breed type was a major source of variation in reproductive life span of beef-type females. F1 Bos indicus crosses and Angus x Herefords were outstanding in longevity. PMID- 1885356 TI - Selection within and across populations in livestock improvement. AB - Genetic evaluations within and across populations (countries, breeds, herds) allow ranking on estimated genetic merit and selecting breeding individuals across populations. Selection within and across populations (combined selection) should by definition always be as good as, or better than, within-population selection, the limiting case. The advantage depends on the sizes of the populations, the number of populations, the initial genetic means, and the correspondence of the breeding objectives in the different populations, as measured by the genetic correlation for economic merit. The advantages of combined selection are evaluated deterministically for a simple case of selecting the best males for use across populations by using a common truncation line over the distributions of EBV for the different populations. Combined selection increases overall response rates in the cooperating populations. Where the initial genetic means are the same, small populations (100 males tested) benefit greatly from combined selection. Large populations (500 to 1,000 males tested) also benefit, but less. The results depend on the increased selection response to scale, response being approximately linear with the logarithm of the number tested. When the initial means differ, the genetically poorer population can catch up in three to five generations and then contribute to the increased responses with combined selection. When breeding objectives differ, selection usually gradually pulls the populations apart and they make less and less contribution to each other and finally become separate. These results have implications for breeding strategies. Their application would affect structures of populations and rates of genetic change possible by selection. PMID- 1885357 TI - Calving and weaning characteristics of Angus-, Gray Brahman-, Gir-, Indu-Brazil-, Nellore-, and Red Brahman-sired F1 calves. AB - Calving and weaning data from crossbred calves sired by five Bos indicus breeds and one Bos taurus breed were evaluated. Data included calving and weaning records of F1 calves out of multiparous Hereford cows and sired by Angus, Gray Brahman, Gir, Indu-Brazil, Nellore, and Red Brahman bulls. At calving, Angus sired calves had shorter gestations and lower (more desirable) calving ease scores and were smaller than Bos indicus-sired calves. Among the Bos indicus crosses, Gir calves had the shortest gestations, lowest calving ease scores, lightest birth weights (P less than .05), and smallest cannon bone lengths and heart girths. Nellore calves had the longest gestations (P less than .05) and largest heart girths. Calves by Indu-Brazil sires had the highest calving ease scores, highest birth weights (P less than .05), and greatest cannon bone lengths (P less than .05). Gray Brahman- and Red Brahman-sired calves were similar and intermediate for all calving characters. At weaning, Angus-sired calves had gained slightly faster than the Gir crosses and weighed more but were shorter at the hip than Gir crosses. Gir calves gained the least preweaning, weighed the least, and were shortest at weaning of the Bos indicus crosses. The Nellore and Indu-Brazil crosses were intermediate in preweaning gain and weaning weight to the Gir and the Red and Gray Brahman but were tallest at weaning. Gray Brahman and Red Brahman calves gained the most and were heaviest at weaning but were not as tall as the Nellore and Indu-Brazil. PMID- 1885358 TI - Postweaning growth of unselected Hereford and Angus cattle fed two different diets. AB - Two unselected herds of purebred Hereford and Angus cattle were created and their progeny evaluated during a 4-yr period (1964 to 1967) for 168-d postweaning gain when they were fed either a high- or medium-energy diet. Birth weight and 200-d adjusted weaning weight also were measured and the importance of sire x diet interactions for postweaning gain examined. Year effects were significant (P less than .001) for all traits in Herefords and for postweaning gain in Angus. Postweaning gain of both breeds increased in successive years, but no trend was observed for birth and 200-d weights. Bulls were heavier than heifers (P less than .05) for all three traits in both breeds. Hereford and Angus calves receiving the high-energy diet gained more (P less than .001) than their contemporaries fed the medium-energy diet. Sire differences were significant for birth weight in Herefords and for all three traits in Angus. Sire x diet interactions were not significant for postweaning gain in either breed. Genetic correlations were calculated by two methods: the two-way ANOVA approach using sire and sire x diet interaction variance components and the one-way ANOVA approach in which gains by progeny of each sire on each diet were considered to be two distinct traits. The genetic correlations for gain in Herefords could not be estimated by either method because of negative sire variance component estimates. The genetic correlations for gain in Angus were 1.08 for the two-way ANOVA method and 1.43 +/- .64 for the one-way ANOVA method. These results indicate that sires ranked the same based on progeny performance when fed either diet. PMID- 1885359 TI - Body measurements of newborn calves and relationship of calf shape to sire breeding values for birth weight and calving ease. AB - Body measurements on Angus- (n = 374) and Polled Hereford-sired (n = 438) calves were used to quantify calf shape via multivariate factor analysis, and measurements on Polled Hereford-sired calves were further used to investigate relationships between calf shape and sire expected progeny differences (EPD) for birth weight and first-calf calving ease. Calf birth weight, head circumference, shoulder width, hip width, heart girth, cannon bone circumference and length, and body length were recorded at 24 h postpartum. Sire birth weight EPD was positively associated (P less than .05) with all calf measures but only with head and cannon circumference after adjustment for phenotypic birth weight and gestation length. Thus, at constant birth weight, calves from higher birth weight EPD bulls tended to have larger cannon and head circumferences. Calving ease EPD was negatively related (P less than .05) to all calf measures except shoulder width. After adjustment for birth weight, only cannon circumference was associated with calving ease EPD, and this effect was removed by additional adjustment for birth weight EPD. Thus, at constant birth weight, bulls with higher EPD for calving ease sired calves with smaller cannon circumference, but at constant birth weight EPD, body measures were not associated with calving ease EPD. Factor analysis defined underlying skeletal width and frame components of shape (independent of birth weight) for both sire breeds. Calf shape differed among sires and was in part explained by birth weight EPD. No additional variation in shape was explained by calving ease EPD. Calf shape seemed to add no information for prediction of dystocia to that provided by birth weight EPD. PMID- 1885360 TI - Body measurements of crossbred calves sired by Simmental bulls divergently selected for progeny first-calf calving ease in relation to birth weight. AB - Simmental bulls (n = 27) were divergently selected on linear model first-calf calving ease expected progeny difference (CEPD) relative to birth weight expected progeny difference (BEPD) so that body measures of calves from sires whose progeny tended to be born either with more or less dystocia than expected from BEPD could be obtained. At birth, calf weight, head circumference, shoulder width, hip width, heart girth, cannon bone circumference and length, and body length were recorded for 204 calves. These measures had also been obtained from the Polled Hereford X Angus dams of the calves at their births. Sire differences (P less than .05) existed for calf cannon bone circumference and length before and after adjustment for gestation length and birth weight of the calf. Sire BEPD was positively associated with cannon and head circumferences independent of phenotypic birth weight and gestation length. No relationship existed between CEPD or threshold model first-calf calving ease expected progeny difference and any calf measure, either before or after adjustment for birth weight. Multivariate factor analysis was used to describe independent components of skeletal width, frame, and thickness after removal of birth weight effects; factors were not related to genetic merit for calving ease or observed calving performance. Independent of weight, newborn calf measures were not highly related to body measures at weaning or to dam birth measures. Body shape differences at constant weight existed in crossbred calves, but they were not related to sire genetic merit for calving ease or measured dystocia. Selection for calf body shape, independent of birth weight, would not reduce dystocia. PMID- 1885361 TI - Heat balance characteristics of limit-fed growing pigs of several breeds kept in groups at and below thermal neutrality. AB - The lower critical temperature (Tcr) and thermoregulatory heat production below Tcr were studied in Norwegian Landrace (N), Finnish Landrace (F), Dutch Landrace (D), and Great Yorkshire (Y) barrows. Animals, weighing 26 kg at the start, were kept in groups for 18, 2-d periods in climate respiration chambers at environmental temperatures (Tenv) between 11 and 26 degrees C. Feeding level of animals in a group was 93 g.kg-.75.d-1 (2.5 times maintenance) and based on mean BW. Great Yorkshire pigs had a higher growth rate and a lower feed to gain ratio than Landrace pigs. Production characteristics of Landrace breeds were similar. The derived Tcr of the breeds was between 18.0 and 20.4 degrees C, the lower value associated with Y pigs and the higher value with F pigs. Thermoregulatory heat production was 6.4 to 11.9 kJ.kg-.75.d-1.degrees C-1 and did not differ between breeds. Radiant surface temperature (Trs) of pigs increased by .4C degrees (= bTrs) when Tenv was raised by 1.0 C degrees between 11 and 26 degrees C. In D pigs, bTrs was higher than in other pigs. Radiant surface temperature was related to backfat thickness; bTrs was increased with greater backfat thickness. PMID- 1885362 TI - Use of trenbolone acetate and estradiol in intact and castrate male cattle: effects on growth, serum hormones, and carcass characteristics. AB - The effects of anabolic implant on growth, carcass characteristics, and serum hormones were examined in 30 young bulls and steers fed a growing diet then a finishing diet. In a 2 X 3 factorial arrangement, steers and bulls received an implant of trenbolone acetate (TBA), TBA and estradiol-17 beta (E2), or no implant. Blood samples were taken serially (every 20 min for 6 h) at intervals during the growing and finishing phases. Percentage of DM, fat, protein, and ash and Warner-Bratzler shear test were measured and taste panel evaluations of the 9 10-11 rib section were obtained. Treatment with TBA and E2 increased weight gain in steers but not in bulls. There were no differences in feed efficiency, serum growth hormone (GH), and cortisol concentrations between bulls and steers or between treated groups and controls in bulls or steers, although during the finishing phase mean GH concentrations in treated steers were twofold higher than in controls and were similar to those in the bull groups. Serum insulin-like growth factor-I (IGF-I) increased twofold during the growing phase, then remained at that level. Steers implanted with TBA and E2, which had the highest gains among the steer groups, had the highest serum GH and IGF-I. Longissimus steaks from bulls treated with TBA alone or TBA and E2 were comparable to steaks from steers in the shear test. Taste panelists found steaks from TBA- and E2-treated bulls to be similar in tenderness and connective tissue to steaks from steers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1885363 TI - Effects of exogenous porcine growth hormone (pGH) on growth, carcass traits, reproductive characteristics, and meat sensory attributes of young boars. AB - Two studies were conducted to examine the possible reduction in odors in fat and loin samples from boars treated with porcine growth hormone (pGH). In Exp. 1, boars were treated with either 0 (control: C), 3.5, or 7 mg of pGH daily from 72 to 119 kg BW. Treatment with pGH improved feed efficiency (P less than .05) but did not affect ADG, concentrations of testosterone in plasma, or aroma of cooked meat (all P greater than .05). Boars treated with pGH had less average backfat depth and marbling (both P less than .05) than C boars. Tenderness of the meat was reduced (P less than .05) by pGH treatment compared with control boars and contemporary barrows. Fat odors of pGH-treated boars were intermediate to those of barrows and control boars. In Exp. 2, boars were treated with vehicle (C) beginning at 62 kg BW or with 5 mg of pGH from either 65 kg (L) or 77 kg (H) BW to 118 kg BW. Average daily gain was higher in Group H than in Group C; Group L was intermediate. Average fat depth was lower (P = .0005) in Groups H and L than in Group C. Treatment had no effect on loin eye area, muscle marbling, texture, firmness, or pH, but color scores of Groups L and H tended to be different from each other (P = .06), and Group H muscle had more free water than that of Groups C and L (P less than .05). Weights of reproductive organs were unaffected by treatment (both experiments: P greater than .05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1885364 TI - Effect of colostral fat level on fat deposition and plasma metabolites in the newborn pig. AB - The effects of colostral fat level on fat deposition and plasma concentrations of glucose, insulin, and free fatty acids (FFA) were determined in 28 newborn pigs during the first postnatal day. Soon after birth, pigs were allotted to four treatments groups. Group 1 was killed at birth. The remaining pigs were fed intragastrically sow colostrum that contained high (10.2%; HFC), normal (4.8%; NFC) or low (1.0%; LFC) levels of total fat at the rate of 15 to 18 g/kg birth weight at 65- to 70-min intervals. A total of 21 feedings was provided and pigs were killed 1 h after the last feeding. Body fat deposition increased linearly (P less than .01) with the amount of ingested fat by .32 (+/- .04) g per 1-g increase in fat intake. Fatty acid composition of the pigs changed toward that of the colostrum with increased fat in colostrum. More liver glycogen was lost (P less than .01) in pigs given LFC. Plasma concentrations of glucose and insulin were similar in pigs fed HFC and NFC. After the 11th feeding (14 h postnatal), LFC resulted in lower plasma glucose concentrations (P less than .05) than HFC or NFC. Plasma insulin concentrations also were lower in pigs fed LFC. Plasma FFA concentrations remained unchanged in pigs fed LFC but increased with both fat content in colostrum (P less than .05) and time (P less than .05) in the other two groups. Colostral fat plays a major role in the supply of energy and in glucose homeostasis in the neonatal pig. PMID- 1885365 TI - Effect of protein source and fumaric acid supplementation on apparent ileal digestibility of nutrients by young pigs. AB - Two experiments were conducted to determine the apparent ileal digestibility of DM and N by young pigs fed diets supplemented with different protein sources or organic acids. Pigs were surgically fitted with silicone cannulas at 2 wk of age. Following surgery, pigs were allowed to recuperate with their dams while suckling normally. After weaning at 24 d, pigs were assigned to treatment diets at 28 d of age. A 3-d adjustment and 4-d collection sequence was followed for the duration of the 4-wk experiment. Four treatment diets were fed in each experiment in a weekly rotation until each diet had been fed to each pig. Diet samples and digesta collected through the ileal cannulas were analyzed for chromic oxide (used as an indigestible marker), DM, and N. Pigs in Exp. 1 were fed isolysinic (1.0%) corn-based diets supplemented with casein, soybean meal, soy protein concentrate, or isolated soy protein. Casein addition resulted in improved DM (P less than .001) and N (P less than .05) digestibility but reduced gain (P less than .05) compared with the average of the soy protein sources. Nitrogen from diets formulated with soybean meal was digested more completely (P less than .05) than N from diets based on soy protein concentrate and isolated soy protein. Experiment 2 was an evaluation of the effect of dried skim milk (25%) and fumaric acid (2%) addition on apparent ileal digestibility of N and DM in corn-soybean meal diets. Addition of dried skim milk improved DM (P less than .01) and N (P less than .05) digestibility and daily gain (P less than .001). Fumaric acid supplementation did not affect nutrient digestibility or gain (P greater than .10). PMID- 1885366 TI - The effect of dietary potassium and chloride on cation-anion balance in swine. AB - The apparent retention and excretion of cations and anions were evaluated in 20 growing pigs to study the mechanisms by which an interaction between dietary K and Cl levels affected growth. All pigs maintained a positive retention of K+ and Cl- regardless of the dietary levels. The K x Cl interaction observed in growth studies previously but not in this study could not be explained by a simple interaction of one ion on the retention of the other. When pooled across dietary Cl levels, an increase in dietary K levels from .10 to .60% resulted in a calculated increase in daily K+ intake of 4.86 meq/kg of BW. Sixty percent (2.99 meq) of the increased K+ intake was excreted in the urine and counterbalanced by a decrease in urine NH4+ (3.06 meq). This decrease in NH4+ excretion could account for essentially all of the increase in N retention (3.51 mmol) observed when dietary K levels were increased from .10 to .60%. Thirty-three percent of the increased K+ intake (1.62 meq) was retained, but the counter ion could not be determined. Retention of Cl- was not changed as dietary K levels were changed. When dietary Cl levels were increased from .03 to .57%, 69% (4.06 meq) of the calculated difference in Cl- intake (5.90 meq) was excreted in the urine, which must have been counterbalanced by a decrease in undetermined organic anions (1.77 meq) and HPO4 = (1.50 meq) excretion, with a tendency for an increased NH4+ (.82 meq) excretion. The counter ions required to balance the increased Cl- retention (1.82 meq) as dietary Cl levels were increased from .03 to .57% could not be identified. Shifts in the retention and urinary excretion of Ca++, Na+, HCO3-, and SO4= did not seem to be quantitatively important in identifying the mechanisms by which dietary K and Cl levels alter growth. Based on these results, we conclude that alterations in growth caused by changes in dietary K and possibly Cl levels are mediated via mechanisms involving renal NH4+ metabolism. PMID- 1885367 TI - Effect of vitamin E and copper on the vitamin E status and performance of growing pigs. AB - A 13-wk trial was conducted with 32 pigs to determine the effects of dietary Cu (250 ppm) and alpha-tocopheryl acetate (ATA, 22 IU/kg) on the performance, serum enzymes, serum and tissue tocopherols, and antibody production in growing pigs. Pigs were fed corn-soybean meal diets containing 21% CP the first 4 wk and 18% CP during the rest of the trial. All feed was stored a minimum of 14 d before it was fed. The addition of Cu decreased (P less than .01) the concentration of alpha tocopherol in the feed. alpha-Tocopherol concentrations were less than .01 mg/kg in the starter diet and less than 2 mg/kg in the grower diet after 14 d of storage. Supplemental Cu or ATA had no effect on ADG, feed intake, or gain:feed during the first 4 wk. During wk 5 to 13, the addition of Cu to diets containing no ATA increased daily feed intake and decreased gain:feed, but with ATA addition, feed intake decreased and gain:feed increased, resulting in a Cu x ATA interaction (P less than .05). The addition of Cu or ATA had no effect (P greater than .1) on serum glutathione peroxidase or lactic dehydrogenase activity. Serum tocopherols were reduced (P less than .05) by the addition of Cu during wk 1 to 4, 6 (P less than .01), and 7 (P less than .05) and increased (P less than .01) by ATA addition during the entire experiment. The addition of ATA increased the tocopherol concentrations in bile, ham, heart, pancreas, kidney, spleen, liver, psoas and longissimus muscle (P less than .01), kidney fat, backfat, and adrenal gland (P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1885368 TI - Uterine influences on the formation of subnormal corpora lutea in seasonally anestrous ewes. AB - The hypothesis that subnormal luteal function after induced ovulation in anestrous ewes was the result of uterine influences exerted during the periovulatory period was tested. Crossbred ewes (n = 27) in seasonal anestrus were induced to ovulate by administration of 12 doses of 250 ng of LHRH at 2-h intervals, followed immediately by a bolus injection of LHRH (250 micrograms; d 0). Ewes were unilaterally hysterectomized on either d -3 (PRELHRH) or 2 (POSTLHRH). Daily blood samples were collected and assayed for progesterone (P4) and 13,14-dihydro-15-keto-prostaglandin F2 alpha (PGFM). All ewes were slaughtered on d 10, and corpora lutea (CL) were collected, weighed, and assayed for concentration of P4. All ewes that ovulated exclusively in the ovary ipsilateral to the remaining uterine horn had a transient increase in plasma P4 of 2 to 3 d (short luteal phase). In ewes with at least one CL in the isolated ovary, elevated plasma P4 was maintained after hysterectomy but was consistently lower (P less than .05) in POSTLHRH ewes than in PRELHRH ewes. Concentrations of PGFM did not differ between treatments. The CL ipsilateral to the remaining uterine horn weighted less (P less than .01) and contained less P4 (P less than .01) than contralateral CL. These data confirm the hypothesis that premature regression of subnormal CL is uterine-dependent in a local fashion. Presence of the uterus during the follicular and(or) early luteal phase inhibited subsequent luteal function in seasonally anestrous ewes. PMID- 1885369 TI - Endocrine changes and ultrasonography of ovaries in suckled beef cows during resumption of postpartum estrous cycles. AB - Changes in follicular and luteal structures were assessed and concentrations of estradiol and progesterone were measured in 13 Hereford X Angus suckled beef cows during resumption of estrous cycles. Transrectal ultrasonography was used to monitor follicular size, ovulation, and formation and regression of the corpus luteum (CL). The interval from parturition to first postpartum ovulation (FO) was 82 +/- 4.7 d. Serum progesterone remained low before FO. One cow exhibited standing estrus, two cows showed other signs of estrus, and 10 displayed no signs of behavioral estrus preceding FO. All cows exhibited standing estrus before the second postpartum ovulation (SO). All cows had a short luteal phase after FO, with an average interval of 8.5 +/- .2 d between FO and SO. Concentrations of estradiol in serum during the 8 d preceding ovulation were similar before FO and SO. Maximal diameter of the preovulatory follicle was similar before FO and SO. However, the ovulatory follicle was larger in diameter at 2 d (P = .02) and 3 to 8 d (P less than .005) before FO than before SO. The time from detection until ovulation was less (P = .005) for the ovulatory follicle preceding SO than for the follicle associated with FO (8.5 vs 10.2 d, respectively, SE = .4). The second-largest follicle was larger (P less than .005) in diameter during the 8 d preceding the FO than before the SO. The difference in size between the ovulatory follicle and the second-largest follicle on the day before ovulation was greater (P less than .005) preceding SO than preceding FO (8.7 vs 6.6 mm, respectively, SE = .4).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1885370 TI - Responses of cortisol and prolactin to sexual excitement and stress in stallions and geldings. AB - Sexual stimulation induces rapid secretion of cortisol and prolactin (PRL) in stallions. Experiment 1 was designated to determine whether stallions associated location and(or) procedure with previous sexual stimulation in that location. After a control period on d 1, four stallions were exposed to an estrous mare for 5 min on d 2. On d 3, 4, 5, and 6, the same procedure was followed with no mare present. Concentrations of PRL and cortisol increased (P less than .05) after mare exposure on d 2 but did not vary (P greater than .05) on d 1, 3, 4, 5, or 6. In Exp. 2, six stallions were used to determine the short-term effects of 1) sexual stimulation, 2) acute physical exercise, 3) restraint via a twitch (twitching), 4) epinephrine administration, and 5) no stimulation on plasma concentrations of PRL and cortisol. Stallions received one treatment per day separated by 2 d of no treatment. Concentrations of cortisol increased (P less than .05) within 10 min after sexual stimulation, exercise, twitching, and epinephrine administration but not during control bleedings. Concentrations of PRL increased (P less than .05) immediately after sexual stimulation, exercise, and twitching but not after epinephrine administration or during control bleeding. In Exp. 3, the same five treatments were administered to six geldings. Concentrations of cortisol increased (P less than .05) after epinephrine administration, exercise, and twitching but not after sexual stimulation or during control bleedings. Concentrations of PRL increased (P less than .05) after exercise and sexual stimulation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1885371 TI - Distribution of time to first postpartum estrus in beef cattle. AB - The function of a distribution that describes postpartum interval (PPI) under any experimental treatment is useful for simulation modeling, understanding the effects of stimuli on the endocrine system, and estimating the average PPI in experiments terminated before all animals have expressed estrus. This study was undertaken to compare the fit of three statistical distributions, the Weibull, the log-normal, and the linear hazard rate (LHR), to the empirical distribution of PPI for five treatment regimens: no bull exposure postpartum, bull exposure from 53 d postpartum, bull exposure from 3 d postpartum, and bull exposure from an average of 63 d postpartum for 2-yr-old cows and for mature cows. The Weibull and the log-normal distributions deviated considerably from the empirical distribution. The LHR distribution with parameters changing over three different regions gave an excellent fit. The resulting hazard rate (instantaneous probability of a cow expressing her first estrus at time t postpartum) revealed a low probability of expressing estrus within 27 d postpartum (43 d for 2-yr-olds). For cows not exposed to bulls, the hazard rate increased slowly with time. For cows exposed to bulls after 3 d postpartum, the hazard rate increased rapidly between d 27 and d 50. For cows exposed to bulls after 53 d postpartum, the hazard rate increased instantaneously approximately 12 d after initial exposure to bulls. This increase was also seen when cows were exposed to bulls beginning at a constant date (at an average of 63 d postpartum). Because of lack of fit, the Weibull and the log-normal distributions should not be used in survival analysis of PPI.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1885372 TI - The effect of pure and partial yellow endosperm sorghum grain hybrids on site and extent of digestion in beef steers. AB - To compare the effects of sorghum grain hybrids on site and extent of digestion, two yellow (Y1 and Y2), two cream (C1 and C2), and two hetero-yellow (HY1 and HY2) sorghum grains were fed (1.85% BW, DM basis) in an 81% dry-rolled grain diet to steers (342 kg BW) equipped with ruminal, duodenal, and ileal cannulas within a 6 X 6 Latin square. Yellow (YEL) hybrids had a homozygous yellow endosperm and a yellow seed coat; cream (CREAM) and hetero-yellow (HET-YEL) hybrids had a heterozygous (partial) yellow endosperm, with white or red seed coats, respectively. Total tract starch digestibility (percentage) was greater (P less than .10) for CREAM and HET-YEL (82.3) than for YEL (78.9), primarily because of greater (P less than .05) starch digestion in the large intestine. Ruminal starch digestibility (percentage) was greater (P less than .10) for HET-YEL (73.2) than for CREAM (66.3) and was a larger proportion of total tract digestion for HET-YEL (90.6) than for CREAM (80.1). Ruminal starch digestion was correlated negatively (r = -.46; P less than .08) with ruminal escape of feed N. Prececal starch digestibility (average 76.2%) was more strongly correlated with ruminal digestibility (r = .69; P less than .01) than with digestion in the small intestine (r = .41; P = .12). Total tract nonammonia N (NAN) digestibility (percentage) was greater (P less than .10) for CREAM than for HET-YEL, greater for Y1 (P less than .10) than for Y2, greater for C2 (P less than .05) than for C1, and greater for HY2 (P less than .05) than for HY1. Flow of NAN to the duodenum was correlated negatively (r = -.55; P less than .05) with prececal starch digestion. Small intestinal NAN disappearance (g/d) was greater (P less than .01) for HY1 (76.0) than for HY2 (52.2). Microbial N flow (r = .88; P less than .01), but not feed N flow (r = .17; P = .52), to the duodenum was correlated with partial NAN digestibility in the small intestine. Hybrids differed in site and extent of digestion. Differences were generally larger for N than for starch. PMID- 1885373 TI - Technical note: a double L intestinal cannula for cattle. AB - A double L-shaped intestinal cannula was developed in an attempt to overcome problems observed previously with simple T-type cannulas. The cannula was constructed from cyclopolyvinyl chloride water pipe fittings. Construction materials were fairly rigid, but by connecting the split cannula pieces with elastic castration bands the cannula had some flexibility. Placing a short cone over the exposed cannula barrel reduced mechanical damage to the intestine. The double L cannula required a much smaller incision in the intestine during surgical insertion than a T-type cannula; it also simplified replacement. Construction is described; use and performance of the cannula has been satisfactory. PMID- 1885374 TI - Effects of lactational status on forage intake, digestibility, and particulate passage rate of beef cows supplemented with soybean meal, wheat middlings, and corn and soybean meal. AB - Sixteen mature, lactating (453 kg) and 16 nonlactating (487 kg) Hereford and Angus x Hereford cows were used to determine effects of different dietary supplements and lactational status on forage intake, digestibility, and particulate passage rate. Supplement treatments and amounts fed (kg/d) were as follows: control, 0; and equal daily amounts of CP from soybean meal (SBM), 1.36; wheat middlings (WM), 3.41; or a blend of corn and soybean meal (corn-SBM; 22% corn and 76% SBM), 3.41. Cows were fed supplements at 0800 and had ad libitum access to prairie hay (4.9% CP) in stalls from 0800 to 1100 and from 1300 to 1600 for three 17-d periods. Lactational status and supplement type did not interact (P greater than .50) for hay DMI, DM digestibility, or particulate passage rate. Cows fed SBM ate more hay DM (P less than .01) and had greater hay DM digestibility (P less than .01) than did cows in other treatment groups. Average hay DMI (kg/100 kg of BW) was 1.95, 2.16, 1.94, and 1.89, and hay DM digestibility was 52, 61, 55, and 53% for control, SBM, WM, and corn-SBM supplements, respectively. Total diet DM digestibility was increased by supplementation (P less than .01), but no differences (P greater than .18) were observed among supplements. Lactating cows ate more (P = .13) hay DM (2.11 vs 1.87 kg/100 kg of BW) and had greater (P less than .05) fecal output (4.6 vs 4.3 kg/d) than did nonlactating cows. Dry matter digestibility and particulate passage rate were not affected (P greater than .35) by lactational status.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1885375 TI - Influence of protein supplementation on site and extent of digestion, forage intake, and nutrient flow characteristics in steers consuming dormant bluestem range forage. AB - Four multicannulated Holstein steers (initial BW 424 +/- 16 kg) were used in a 4 x 4 Latin square to determine the influence of protein supplementation on forage intake, site and extent of digestion, and nutrient flow in steers consuming dormant bluestem-range forage (2.3% CP). Treatments were 1) control, no supplement; 2) 1.8 kg of low-protein supplement, 12.8% CP (Low-CP); 3) 1.8 kg of moderate-protein supplement, 27.1% CP (Mod-CP); and 4) 2.7 kg of dehydrated alfalfa pellets, 17.5% CP (Dehy). The Dehy supplement was fed to provide the same amount of CP/d as Mod-CP, and all supplements provided similar amounts of ME/d. Forage DMI was increased (P less than .05) by feeding Mod-CP and Dehy. Ruminal OM digestibility was 39% greater (P less than .05) for the Mod-CP and Dehy supplementations than for the Low-CP supplementation and control. Ruminal CP digestibility was negative for all treatments, and control (-326%) was less (P less than .05) than supplemented treatments (average -27%). Total tract OM digestibility was greatest (P less than .10) for steers fed Mod-CP and least for control steers; Low-CP and Dehy steers were intermediate. Total tract NDF digestibility tended (P = .15) to be less with Low-CP than with Mod-CP and Dehy. Duodenal N flow was greater (P less than .05) with Mod-CP and Dehy than with Low CP and control. In summary, supplementation with Mod-CP increased forage intake, digestion, and duodenal N flow compared with Low-CP or control; however, the response was similar when Mod-CP and Dehy supplements were fed to provide equivalent amounts of CP and ME daily. PMID- 1885376 TI - Relationships of body weight, forage composition, and corn supplementation to feed intake and digestion by Holstein steer calves consuming bermudagrass hay ad libitum. AB - Holstein steer calves (101 to 350 kg BW) consumed bermudagrass hay ad libitum without or with supplemental ground corn up to 1.0% of BW. As BW increased, total DMI increased quadratically (-2.459 + .05448 [BW]-.000073 [BW2] + .540 [corn DMI]; R2 = .83, sy.x = .655). Each kilogram of corn DM decreased bermudagrass DMI by .46 kg. Total digestible OM intake (kg) increased with BW and corn supplementation (.314 + .0127 [BW] + .441 [corn OM intake]; R2 = .79, sy.x = .444). Feed intake level accounted for approximately 2.5 times more variability in total digestible OM intake than digestion did. Corn supplementation decreased digestion of bermudagrass NDF (62.50 - 8.468 [corn DMI, % BW]; R2 = .13, sy.x = 8.121), with a similar decrease across BW. Increasing bermudagrass DMI (% of BW) decreased bermudagrass NDF digestion slightly, but variation accounted for was only 33% of that attributable to corn DMI (% of BW). Concentrations of common fiber fractions (NDF, ADF, cellulose, hemicellulose, and ADL) in bermudagrass explained very little variation in feed intake and digestion, indicating considerable influence of other factors. Bermudagrass intake and digestion were not related, and no substantial interactions were observed among steer BW, corn level, and bermudagrass composition. PMID- 1885377 TI - Influence of passage model, sampling site, and marker dosing time on passage of rare earth-labeled grain through Holstein cows. AB - Three duodenally cannulated, lactating Holstein cows were dosed with rare earth labeled grain to evaluate effects of passage model, sampling site, and marker dosing time on digesta passage parameters. Cows were given ad libitum access to feed twice daily. Rare earth-labeled grain (applied by the 24-h immersion technique) was fed immediately before (Dy) or 2 h after (Yb) the morning feeding, and duodenal digesta and feces were sampled. Marker excretion curves were fit to a two-compartment, biexponential model, using curve peeling or to a series of two compartment models, with one to six orders of gamma time-dependency in the fast compartment, using nonlinear regression. Passage estimates from the curve-peeled, biexponential model were similar to those from the best fit of the nonlinear models, which had three orders of gamma time-dependency. Ruminal passage rate of grain, averaged across models, sampling site, and dosing time, was .077/h. Estimates of time to first appearance of marker at the sampling site and mean retention times were longer (8 vs 1 h and 25 vs 17 h, respectively), but passage rates were similar, when determined from fecal compared with duodenal samples (P less than .05). Marker dosing time did not influence any of the parameters. It is concluded that both curve-peeling (linear regression) and nonlinear regression methods can be equally useful for evaluating passage kinetics of grain in dairy cows and that sampling site and time of marker dosing have little effect on passage parameter estimates. PMID- 1885378 TI - Nitrogen utilization by ruminants during restricted intake of high-concentrate diets. AB - A series of experiments was conducted to determine the effects of limit-feeding high-concentrate (LFHC) diets on dietary CP requirements of steer calves. When steer calves were fed 80% concentrate diets at 78 g/kg of BW.75, increasing dietary CP resulted in increased ADG (P less than .001). Average daily gain was increased in steers as daily monensin dosage increased from 120 to 180 mg (P less than .05). Increasing the daily monensin dosage to 240 mg did not increase ADG further. There were no (P greater than .10) CP X monensin interactions, suggesting that the monensin response was caused by improved energy utilization and not be the possible protein-sparing effects of ionophores. Steer calves in the second feedyard experiment expressed similar ADG when provided equal NEg as limit-fed, high-moisture ear corn (HMEC) or when given ad libitum access to corn silage. The basal diet did not affect the steers' daily N requirement for growth. Gain per unit of protein intake declined quadratically (P less than .05) with increasing CP intake, indicating that CP requirements were near NRC estimates on both diets. The corn silage-based diet was less digestible (70.3 vs 77.4%; P less than .01) than the HMEC diet when fed to lambs. Fecal output differed (P less than .10) substantially (342 g/d of corn silage vs 205 g/d of HMEC), whereas fecal N output was only slightly higher (6.97 vs 6.34 g/d, respectively; P less than .10). Limited feeding of higher-concentrate diets to steer calves seemed to be an effective management procedure and did not cause acute digestion upset.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1885379 TI - Jay Laurence Lush 1896-1982: a brief biography. PMID- 1885380 TI - Feedlot performance of Brahman x Angus versus Angus steers during cold weather. AB - Ten Angus and 10 Brahman x Angus F1 steers were used in a 184-d trial to compare feedlot performance during cold weather (-9 to 26 degrees C). Both groups of steers were exposed to the same environment for the same amount of time. All steers were fed for the same number of days regardless of frame score to avoid frame score x environment interactions. Brahman x Angus steers were 30.7 kg heavier (P less than .05) than Angus steers at the start of the trial. Differences in age (Brahman x Angus 40 d younger) for the two breed groups did not affect final live weight or carcass weight. Brahman x Angus steers consumed .2% less feed (P less than .05) as a percentage of BW than Angus steers; however, there was no difference in overall feed efficiency. Angus steers had a higher yield grade, more fat at the 12th rib (P less than .05), and graded 90% Choice; only 10% of the Brahman x Angus were graded Choice. Brahman x Angus steers were taller at the hip (P less than .05) and longer from first rib to aitch bone (P less than .05) and from thoracic vertebrae (T12/T13) to point of hock (P less than .05). Hide thickness determined at the neck, belly, and rump was found to be similar (7.7 mm) between the two groups. Sample hair weight and diameter did not differ between groups. Fiber, fat, protein, and DM digestibility coefficients were similar between groups but Brahman x Angus feces had a higher DM content.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1885381 TI - Effects of ractopamine, genotype, and growth phase on finishing performance and carcass value in swine: I. Growth performance and carcass merit. AB - A replicated factorial experiment using 183 individually fed crossbred barrows was conducted. Pigs were fed an 18.5% CP (.95% lysine) diet with 3,594 kcal of ME/kg. The effects of five genotypes (GT): 1) Hampshire (H) x (H x Duroc [D]), 2) synthetic terminal sire line, 3) (H x D) x (Landrace [L] x [Yorkshire (Y) x D]), 4) L x (Y x D), and 5) Y x L; two levels of ractopamine (RAC) treatment: 0 and 20 ppm; and three treatment weight periods (WT): 1) 59 to 100, 2) 73 to 114, and 3) 86 to 127 kg live weight on growth performance and carcass traits were evaluated. Ractopamine increased (P less than .0001) amount (FSL) and percentage (PFSL) of carcass lean standardized to 10% fat content, loin eye area (LEA), and dressing percentage (PDRES) and reduced (P less than .01) amount (DF) and percentage (PDF) of dissected fat. Magnitudes of RAC effects were smaller than those reported by other researchers. Effects of GT and WT on all growth and carcass traits were highly significant (P less than .001) except for those of WT on ADG (P less than .05) and GT on average feed intake (AFI) and backfat thickness at the last rib (BFLR; P less than .05). Genotype 3 performed better for most economically important traits than did GT 1 and 4, suggesting that heterosis existed in GT 3, which essentially was obtained by crossing GT 1 and 4. Among the three treatment periods, WT 2 had the highest ADG. As BW increased from WT 1 to 3, AFI and AFI/ADG ratio (FCR) increased and lean percentage decreased.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1885382 TI - Effects of ractopamine, genotype, and growth phase on finishing performance and carcass value in swine: II. Estimation of lean growth rate and lean feed efficiency. AB - A replicated factorial experiment using 183 individually fed crossbred barrows was conducted. The pigs were fed an 18.5% CP (.95% lysine) diet with 3.594 kcal of ME/kg. The effects of five genotypes (GT): 1) Hampshire (H) X (H X Duroc [D]), 2) synthetic terminal sire line, 3) (H X D) X (Landrace [L] X [Yorkshire (Y) X D]), 4) L X (Y X D), and 5) Y X L; two levels of ractopamine (RAC) treatment: 0 and 20 ppm; and three treatment weight periods (WT): 1) 59 to 100, 2) 73 to 114, and 3) 86 to 127 kg live weight on ADG of dissected lean (ADLG) and fat standardized lean adjusted to 10% fat content (ADSLG) and feed efficiency of ADLG (LFE) and ADSLG (SLFE) were evaluated. Initial carcass lean quantity of each individual animal was determined by a regression equation (R2 = .95) generated from 30 additional barrows (six per GT) slaughtered at 59 kg and 30 (six per GT) untreated pigs slaughtered at 100 kg average live weight. Logarithmic and reciprocal transformations of dependent variables were used to stabilize heterogeneous variances and to improve normality of the residuals. Ractopamine increased (P less than .0001) ADLG, ADSLG, LFE, and SLFE, respectively, by 19.5, 25.0, 19.6, and 25.5%. Differences (P less than .001) were observed among genotypes for all traits, showing that considerable variation existed in the data and indicating that genetic improvement can be realized through the identification and selection of superior genotypes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1885383 TI - Mixtures of wheat and high-moisture corn in finishing diets: feedlot performance and in situ rate of starch digestion in steers. AB - Wheat and high-moisture corn (HMC) were fed singly and in three combinations using dry-rolled wheat (DRW) (ratios of 75:25, 50:50, and 25:75, respectively, Trial 1), or singly and in two combinations using steam-rolled wheat (SRW) (ratios of 67:33 and 33:67, respectively, Trial 2) to finishing beef cattle fed a high-concentrate diet. In situ rate of starch digestion (Trial 3) was measured on grains used in Trial 1 (excluding the 25 HMC: 75 DRW mixture) and ground dry corn. In Trial 1 (132 d), gain/feed did not differ (P greater than .10); however, final weight, hot carcass weight, and ADG decreased linearly (P less than .05) and DMI exhibited a cubic response (P less than .05) as the percentage of wheat in the diet increased. Carcass characteristics were not different. In Trial 2 (113 d), there were no differences attributable to treatment for ADG, DMI, gain/feed, or carcass characteristics. Positive associative responses for gain efficiency (gain/feed) were greatest for the first increment of wheat addition (25% DRW and 33% SRW in Trials 1 and 2, respectively) and for the early portion of the feeding period (57 and 28 d for Trials 1 and 2, respectively), indicating a more rapid diet adaptation and(or) less propensity for subacute acidosis. In Trial 3, the treatment grains or mixtures did not differ in rate of starch digestion. Although the differences were not statistically significant, starch in the 100% wheat diet was digested twice as fast as the 100 or 75% HMC mixtures.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1885384 TI - Comparison of methods for predicting yearling scrotal circumference and correlations of scrotal circumference to growth traits in beef bulls. AB - From 1981 through 1986, BW, hip height, and scrotal circumference (SC) measurements were obtained on 329 bulls at the start of a 140-d gain test (SOT) and every 28 d to the end of test (EOT). Age, overall ADG, weight per day of age, ADG by period, and SC growth (cm/d) were calculated. Data were analyzed in two data sets because age of dam (AOD) and birth weights were unavailable between 1981 and 1983. Correlations of SC to other traits measured and probabilities for bulls attaining 30 or 32 cm SC by 365 d of age were calculated. Two adjusted 365 d SC (365-d SC) were calculated for each individual from regression analysis and from the following formula: 365-d SC = [(SCEOT-SCSOT)/140 d] x [365-ageSOT] + SCSOT. Except for ADG in Data Set 2, breed group differences (P less than .05) were observed for correlations of SC to all growth traits, age, and AOD. To attain 30 cm SC by 365 d of age with nearly 100% probability, Angus, Simmental and Zebu-derived bulls needed a 23-cm SCSOT, whereas continental (other than Simmental) and Polled Hereford bulls required a 26-cm SCSOT. Overall, 365-d SC means calculated by regression analysis or formula method did not differ (P greater than .10) for either data set. PMID- 1885385 TI - Effects of breed, heterosis, age of dam, litter size, and birth weight on lamb mortality. AB - Sources of individual plus maternal effects on lamb mortality were studied in data collected at the U.S. Meat Animal Research Center from 1980 to 1985 for paternal and maternal breeds lambing yearly and for maternal breeds lambing at 8 mo intervals. Records included 16,881 lambs born. Breeds included were Finnsheep (F), Dorset (D), Rambouillet (R), Suffolk (S), Targhee (T), Composite 1 (C1 = F/2, D/4, R/4), Composite 2 (C2 = F/2, S/4, T/4), and Composite 3 (C3 = Columbia/2, S/4, Hampshire/4), Traits analyzed were perinatal, postnatal, and total mortality to 60 d of age and postnatal respiratory, digestive, starvation, injury, and other or unknown causes of mortality. The least squares analyses included breed, year, sire within breed-year, sex, linear and quadratic season and age of dam covariates (Model 1), plus litter size (Model 2), plus birth weight (Model 3), and significant two-way interactions. Age of dam, litter size, and birth weight all had important, often quadratic, effects that differed among breeds. Models 1, 2, and 3, respectively, reduced variation by 8, 10, and 16% for perinatal, 7, 8, and 12% for postnatal, and 9, 11, and 20% for total mortality. In Model 1, breed means ranged from 3.5 to 16.2% for perinatal, 7.2 to 21.1% for postnatal, and 16.7 to 32.8% for total mortality. Respiratory and starvation problems were major causes of postnatal mortality. Heterosis for lamb survival retained in composites was 9% for C1 and 18% for C2. Mortality was 1 to 5% higher for males than for females.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1885386 TI - Genetic and phenotypic variation in sources of preweaning lamb mortality. AB - Information on causes of mortality to 8 wk weaning for 16,881 lambs of 10 line breed groups by 594 sires born over a 5-yr period was analyzed by least squares procedures to estimate sire variance and covariance components within line and year-season. Heritability estimates were approximately 5% for total mortality in the binomial scale and near 10% when converted to a normal scale. Average heritability estimates in the binomial and normal scale were, respectively, 4 and 12% for perinatal and 3 and 7% for postnatal mortality. The heritability estimates for respiratory problems were inconsistent; binomial-scale estimates ranged from 0 to 7% in different populations. Regression adjustment for effects of variation in litter size and birth weight caused only minor changes in the heritability estimates. Comparison of covariances among half-sibs vs full-sibs indicated very large maternal effects on perinatal mortality but smaller and less consistent effects on sources of postnatal mortality. Phenotypic correlations among sources of mortality indicated a 26% greater influence of postnatal than perinatal mortality on variation in total mortality, but both the genetic and phenotypic correlations between those two components were slightly negative. These results suggest that the use of family and progeny test selection for transmitted effects on both perinatal and postnatal lamb viability should be effective. PMID- 1885387 TI - Comparison of crossbred cows containing various proportions of Brahman in spring or fall calving systems: III. Productivity as three-, four-, and five-year olds. AB - Productivity of 3-, 4-, and 5-yr-old crossbred cows containing various proportions (0, 1/4, or 1/2) of Brahman breeding out of Angus or Hereford dams was evaluated using 489 spring-calving and 427 fall-calving records collected over a 4-yr period. Cows were bred to Limousin sires for the first 3 yr and to Limousin and Salers sires the 4th yr. Interactions between crossbred cow group and season of calving were not significant. Percentage of cows exposed to breeding that weaned a calf increased (P less than .01) as proportion Brahman breeding increased, was higher (P less than .01) for cows out of Angus dams than for cows out of Hereford dams, and was higher (P less than .01) for spring calving cows. As the proportion Brahman increased, the percentage requiring assistance at birth decreased, and cows out of Angus dams required less (P less than .05) assistance than those out of Hereford dams. Preweaning ADG, adjusted weaning weight, weaning conformation, weaning condition, and adjusted weaning hip height increased a proportion Brahman breeding increased. Spring-born calves gained .12 kg/d faster (P less than .01) than fall-born calves. However, weight at weaning was similar for the two groups; spring-born calves were weaned at an average age of 205 d, and fall-born calves were weaned at an average age of 240 d. Fall-calving cows were heavier (P less than .05) than spring-calving cows, and 0 and 1/2 Brahman cows were heavier (P less than .01) than 1/4 Brahman cows. These data indicate that Brahman-cross dams can be used to improve reproductive rate and increase preweaning growth rate, and thus weaning weight.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1885389 TI - Evaluation of feed conversion in steers from a diallel of Simmental, Limousin, Polled Hereford, and Brahman beef cattle. AB - A total of 269 steers produced in a four-breed diallel mating design of Simmental, Limousin, Polled Hereford, and Brahman breeds were evaluated for the unadjusted and maintenance-adjusted total feed intake to total weight gain ratio. Time on feed ranged from 184 to 251 d. Covariate adjustments were made separately for age- and 12th rib fat-constant end points. Purebred, general combining ability, and maternal effects and heterosis were estimated. Effects of year, breed of dam, slaughter group, and days on feed accounted for most of the variation in feed conversion. Significantly higher unadjusted cumulative feed/gain ratios were found for steers from Brahman sires and for those from Simmental, Limousin, and Brahman dams. Adjustment to either fat- or age-constant values did not rerank breed groups, but a small reduction in the differences between these groups was detected for fat-constant efficiency. For maintenance adjusted feed intake, progeny of Simmental and Limousin dams were less efficient than those of Polled Hereford and Brahman dams. Negative values for general combining ability, maternal effects, and heterosis would indicate less feed required per unit of weight gain. General combining ability for Polled Hereford crosses was negative and significant for cumulative feed/gain ratios, but no difference among dam breeds was found for the maintenance-adjusted ratio. Maternal effects for Limousin dams were positive and significant for all maintenance-adjusted ratios. Heterosis estimates for specific breed crosses were generally negative and ranged from -.87 to .22. PMID- 1885388 TI - Differences among breed crosses of cattle in the conversion of food energy to calf weight during the preweaning interval. AB - The objective of this study was to determine whether F1 cows that differ in genetic potential for weight at maturity and milk yield vary in the conversion of food energy to calf weight gain. Food intakes and weight change data were recorded by pen for cows and calves from approximately 45 d postpartum. Cows assigned to the study were 7- to 9-yr-old F1s produced by top-crossing Angus, Hereford, Brown Swiss, Chianina, Gelbvieh; Maine Anjou, and Red Poll sires to either Angus or Hereford dams. Calves were sired by Simmentals. Experimental units were pens (10 to 12 cow/calf pairs); pen was replicated within breed of sire in each of 2 yr (n = 24). Calf weight gain and energy consumed by the dams differed among the F1s, as did the ratio of calf weight gain to energy consumed by the calf and cow. Angus or Hereford (35.8), Red Poll (35.7), or Maine Anjou (35.6) F1s produced more calf weight per unit of energy consumed (g/Mcal) by the cow and calf than Chianina (33.1) or Gelbvieh (33.7) F1 females; Brown Swiss cows were intermediate (34.3). Differences in food conversion efficiency exist among breed crosses. These differences seem to be associated with breed cross differences in genetic potential for milk yield and mature weight; an exception to this trend was the Maine Anjou. PMID- 1885390 TI - Metabolizable energy for maintenance of beef-type Bos taurus and Bos indicus x Bos taurus cows in a dry, temperate climate. AB - Metabolizable energy for maintenance (MEm) was estimated using 123 mature cows of eight diverse breed groups. Cows in each breed group were allotted at random 1) to limit-feeding to approximate maintenance or 2) to ad libitum access to feed. The MEm values were calculated by regression of change in body energy on ME intake. The MEm values for mature Hereford, Red Poll, Hereford x Red Poll, Red Poll x Hereford, Angus x Hereford, Angus x Charolais, Brahman x Hereford, and Brahman x Angus breed types were as follows: 145, 169, 148, 149, 144, 152, 139, and 143 kcal.kg-.75.d-1, respectively. Bos indicus-cross cows ranked lowest for MEm/kg.75. Angus x Hereford cows averaged highest in terms of grams of calf weaned per mature female exposed divided by yearly MEm requirement. Hereford x Red Poll reciprocal crosses on average required 640 kcal less total daily MEm per animal than Hereford and Red Poll straightbreds. PMID- 1885391 TI - Effects of selection of data on estimates of breeding values by three methods for litter size, backfat, and average daily gain in swine. AB - Estimated breeding value was calculated based on individual phenotype (SP), an index of individual phenotype and full- and half-sib family averages (SI), or Best Linear Unbiased Prediction (BLUP). Traits considered were litter size (LS), backfat (BF), and ADG. Estimated breeding values were calculated using all data and after deletion of the poorest 5, 10, 15, or 20% of the records for BF and ADG, or 4.8, 8, 13, or 21% of the records for LS. When all data were used, expected genetic gain from BLUP was greater than for SP by 22, 7, and 31% and greater than for SI by 10, 4, and 21% for LS, BF, and ADG, respectively. Expected genetic gain was 4, 0, and 3% lower for LS, BF, and ADG, respectively, for selection on breeding values estimated by SI after the poorest 20% of the records were deleted compared with selection on estimates by SI using all the data. Genetic gain using BLUP on data with the poorest 20% of the records deleted was reduced by 5, 2, and 8% for LS, BF, and ADG, respectively, compared with genetic gain using BLUP on all the data. The advantage in genetic gain of BLUP, with 20% of the poorest records deleted, over SP was 15, 5, and 21% for LS, BF, and ADG, respectively. Although BLUP is affected to a greater degree by deletion of records than is SP or SI, selection of swine using BLUP on field data would improve response to selection over the use of SP or SI. PMID- 1885392 TI - Breed effects and heterosis in advanced generations of composite populations for puberty and scrotal traits of beef cattle. AB - Heterosis effects were evaluated in F1, F2, and F3 generations of females and in the F1, F2, and combined F3 and F4 generations of males in three composite populations of beef cattle. Traits included weight, height, and condition scores at different ages, percentage of females reaching puberty at 368, 410, and 452 d, adjusted age, and adjusted weight of females at puberty and scrotal circumference and paired testicular volume of males. Breed effects were evaluated for the nine parental breeds (Red Poll [R], Hereford [H], Angus [A], Limousin [L], Braunvieh [B], Pinzgauer [P], Gelbvieh [G], Simmental [S], and Charolais [C]) that contributed to the three composite populations (MARC I = 1/4 C, 1/4 B, 1/4 L, 1/8 H, 1/8 A; MARC II = 1/4 G, 1/4 S, 1/4 H, 1/4 A; and MARC III = 1/4 R, 1/4 P, 1/4 H, 1/4 A). Breed effects were significant for all traits evaluated. Heterosis was significant for weight, height, and condition score at all ages and for most measures of puberty in each generation of each composite and for the mean of the three composite populations. Heterosis for age at puberty was largely independent of heterosis effects on 368-d weight. Heterosis was significant for scrotal circumference and paired testicular volume in each generation of each composite and for the mean of the three composite populations. Heterosis effects on scrotal measurements are mediated both through heterosis effects on growth rate and through factors that are independent of growth rate. Correlation coefficients among breed group means and correlations of breed rank for scrotal measurements with puberty traits of females were greater than or equal to .88 (P less than .01) for all puberty traits except weight at puberty, which was not associated with scrotal measurements. There was close agreement in heterosis observed for most traits and expectation based on retained heterozygosity. These results support the hypothesis that heterosis in cattle for size, puberty, and scrotal measurement traits is due to dominance effects of genes. PMID- 1885393 TI - Cortisone arrests growth but enhances the inductive effect of porcine growth hormone on plasma IGF-I concentrations in female rats. AB - The present study was conducted to determine whether corticosteroids influence the inductive effect of growth hormone (GH) on plasma concentrations of insulin like growth factor I (IGF-I). The first experiment was designed to determine the effects of corticosterone alone on basal concentrations of IGF-I. Rats were treated daily for 4 d with 0, 50, 100, 250, or 500 mg of corticosterone/kg of BW. There was a close positive relationship between the dose of steroid injected and plasma concentrations of corticosterone and a close negative relationship between plasma corticosterone and growth. Plasma concentrations of IGF-I showed a positive relationship to dose and plasma concentrations of corticosterone and a negative relationship to growth rate. In the second experiment, rats were treated daily for 21 d with either porcine growth hormone (10 mg of pGH/kg of BW), pGH plus corticosteroid, or vehicle. The dose of steroid administered was increased every 3 d until the mean weight gain of the group was zero. Animals treated with pGH alone gained significantly more weight than controls. This growth response was not impaired significantly by corticosterone acetate at doses up to 500 mg/kg of BW. The more potent corticosteroid, cortisone, arrested the growth of pGH treated rats at a dose of 80 mg/kg of BW, however. Plasma concentrations of IGF-I were increased by pGH treatment (57%) and increased further by concurrent cortisone treatment (212%). In summary, corticosteroids increase plasma concentrations of IGF-I and enhance the inductive effect of pGH on this hormone despite their catabolic actions. PMID- 1885394 TI - Computer simulation model of swine production systems: III. A dynamic herd simulation model including reproduction. AB - A dynamic herd simulation model for a swine production unit has been developed. The model is discrete and stochastic and the appropriate random distributions have been defined from the literature or empirically estimated. Theoretical concepts and relationships presented previously are used to simulate growth and the overall life cycle of individual animals. Simulated animals are young pigs (from birth to slaughter age), gilts, and sows. Animal events are farrowing, weaning, mating, end-nursery (transfer from nursery to the growing-finishing facility), and slaughter and are processed individually using a next-event scheduling orientation package. Animals within the herd are culled for different health and reproductive reasons. Genetic parameters, diet composition, and herd management are input variables chosen by the user. The effects of nutrition, genetics, season, and other factors on several reproductive parameters are considered. Model evaluation is performed by studying the output of the model under specified herd situations. The herd model adequately simulates animal flow and dynamics of the herd. PMID- 1885395 TI - Effect of limited feed intake on growth of subcutaneous adipose tissue layers and on carcass composition in swine. AB - Little is known about the function of individual backfat layers in swine. Our objective in this study was to evaluate differential growth of each backfat layer in pigs fed different amounts of the same diet. Relationships of growth of backfat layers to deposition of carcass protein and ether extract were also studied. Feed intake levels were ad libitum, 92.5% of ad libitum, and 85% of ad libitum for 36 barrows averaging 95 d of age and 37.8 kg of weight at the start of the study. Chemical composition of the carcass soft tissue was determined at the end of the 84-d study. Daily gain tended to decrease (P less than .10) and conversion of feed to gain improved (P less than .15) as feed intake decreased. The daily depositions (g/d) of protein and ether extract were 62.9 and 205 for the ad libitum group, 61.1 and 176 for the 92.5% intake group, and 59.3 and 153 for the 85% intake group, respectively. The compositional effect of limiting feed intake for 84 d was to produce less carcass soft tissue of greater lean content. Overall backfat depths were 31.5, 29.6, and 27.8 mm for the ad libitum, 92.5, and 85% intake groups, respectively. The outer backfat layer differed among groups; the 92.5 and 85% groups were thinner than the ad libitum group. Relative to the ad libitum group, the change in depth of the middle backfat layer was 86 and 75% for the 92.5 and 85% intake groups (P less than .01). The inner backfat layer was not affected significantly by level of feed intake.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1885396 TI - Effects of the beta-adrenergic agonist isoproterenol on protein accretion, synthesis, and degradation in primary chicken muscle cell cultures. AB - Seven-day-old primary myotube cultures derived from embryonic chicken limb muscles were used to determine the effects of the beta-adrenergic agonist isoproterenol (ISO) on muscle protein metabolism in vitro. Isoproterenol increased (P less than .05) total protein accumulation after 2 h of acute exposure and after chronic exposure for 24 and 48 h. Isoproterenol did not consistently retard rate of protein degradation of the total protein (TP), myofibrillar protein (MFP) pools, and myosin heavy-chain subunit (MHC); degradation of these protein pools tended to be slowed by inclusion of ISO in the culture medium. After acute treatment of 1 X 10(-4) M ISO for 2 h, TP, but not MFP and MHC, synthesis rate was increased, and after chronic exposure to 1 X 10( 4), 1 X 10(-5), and 1 X 10(-6) M ISO, TP, MFP, and MHC synthesis rates and net accumulation of TP, cytoplasmic protein, and MHC fractions were enhanced (P less than .05). The beta-adrenergic antagonist propranolol (1 X 10(-5) M) blocked chronic stimulatory effects of ISO. Furthermore, after 48 h of exposure to ISO, effects on protein synthesis were less pronounced than those observed after 24 h of exposure. Isoproterenol imparted a more pronounced effect on protein synthesis than on protein degradation, indicating that increased muscle protein accretion observed in animals after ISO treatment is likely a function of enhanced protein synthesis. PMID- 1885398 TI - National beef market basket survey. AB - Beef retail cases in supermarkets in 12 cities across the United States were surveyed for fat thickness measurements, cut representation, package weights and counts, and case space allocation. Randomly selected retail cuts were purchased and transported to Texas A&M University, where they were dissected into separable components. Samples of ground beef were obtained for chemical analysis. Over 42% of the beef retail cuts had no external fat, and approximately 75% of all cuts were boneless. The overall mean fat thickness for all retail cuts in the beef case was .31 cm, and the overall mean fat thickness for steaks and roasts from the major primals - chuck, rib, loin, and round - was .38 cm. The average percentage of separable lean was 79.0%, separable fat was 12.3%, and bone and connective tissue was 8.7%. Retail cuts had more than twice as much separable seam fat as separable external fat. Beef steaks and roasts had 27.4% less separable fat than values from USDA Agriculture Handbook 8-13. Of the ground beef surveyed, 37% was regular, 40% was lean, and over 22% was extra lean. Retail ground beef had approximately 10% less fat than values from USDA Agriculture Handbook 8-13. PMID- 1885397 TI - Effect of porcine somatotropin, stress susceptibility, and final end point of cooking on the sensory, physical, and chemical properties of pork loin chops. AB - Forty-eight pigs of three known stress susceptibility classes were injected daily with porcine somatotropin (pST; 4 mg/d) or a placebo. Each pig was injected in the neck once daily until taken off test, starting when the pigs weighed 59 kg. The pST treatment was terminated at weekly intervals when individual pigs reached 109 kg, but animals continued to be fed for six additional days to allow for required withdrawal time. The effect of pST and stress classification on the sensory, physical, and chemical characteristics of pork chops was observed. Also, the effect of two end-point temperatures (71 and 77 degrees C) on the sensory attributes was observed. The pST treatment of animals resulted in a small but significant decrease in panel scores for tenderness, juiciness, and flavor. Stress susceptibility class, however, decreased panel scores for tenderness only. The pST treatment reduced intramuscular fat and increased moisture in the longissimus muscle, but stress susceptibility class had no effect on proximate composition. The pST treatment and stress susceptibility decreased and increased Hunter L values of chops, respectively, indicating darker and lighter colors, respectively. Furthermore, a greater end-point temperature reduced sensory scores for tenderness and juiciness. These results suggest that pST treatment does not cause an increased incidence of pale, soft, exudative muscle. Also, the use of a lower temperature of end-point doneness (71 degrees C) should be implemented to optimize palatability of broiled pork chops regardless of pST treatment. PMID- 1885400 TI - Soybean protein solubility in potassium hydroxide: an in vitro test of in vivo protein quality. AB - Experiments were conducted to assess protein solubility in .2% KOH as an indicator of soybean protein quality for chicks and pigs and to assess effects of particle size on protein solubility. As the particle size (micron) of soybean meal (SBM) increased, protein solubility (%) decreased (b = -.0206). In two 9-d chick trials, dehulled SBM (48% CP) was subjected to various autoclaving times and then fed as the sole source of dietary protein to young chicks. Increasing autoclaving times from 0 to 40 min at 120 degrees C resulted in a quadratic decrease in protein solubility. A broken-line model was fitted wherein gain:feed of chicks was plotted as a function of protein solubility. The analysis showed no reduction in feed efficiency with solubilities greater than 59 +/- 1.5% (mean +/- SEM). When solubility was below 59%, however, gain:feed decreased 1.5% for each 1% decrease in protein solubility. The third trial (13 d) was conducted with 7.5 kg pigs fed autoclaved SBM (44% CP) as the primary source of protein. Feed efficiency was significantly decreased when protein solubility was less than 66%. This study showed that protein solubility in KOH was a good index of in vivo soybean protein quality, and that it is important to standardize SBM particle size when applying the KOH assay. PMID- 1885399 TI - Assessment of the influence of dietary vitamin E on sows and offspring in three parities: reproductive performance, tissue tocopherol, and effects on progeny. AB - Sixty crossbred (Yorkshire-Hampshire X Duroc) gilts were fed one of four corn soybean meal diets fortified with .3 ppm Se and 0, 16, 33, or 66 IU of DL-alpha tocopheryl acetate/kg. The study was conducted over a three-parity period to evaluate sow reproductive performance and the vitamin E tissue status of both sows and progeny at various time periods postcoitum and(or) postpartum. The basal diet averaged 8.4 mg of alpha-tocopherol/kg and .38 ppm of Se. Although litter size at birth was lowest (P less than .15) when sows were fed the basal diet, a higher incidence of agalactia when sows were fed the lower dietary vitamin E levels resulted in an increased (P less than .05) litter size at 7 d postpartum as dietary vitamin E increased. Sow serum alpha-tocopherol increased (P less than .01) at each measurement period as dietary vitamin E level increased. Colostrum and milk alpha-tocopherol concentrations increased (P less than .01) as dietary vitamin E level increased, and colostrum values were three to five times higher than at later milks. Colostrum alpha-tocopherol declined by parity from sows fed less than or equal to 16 IU/kg but was similar at each parity for sows fed greater than or equal to 33 IU/kg, resulting in a dietary vitamin E x parity interaction (P less than .01). The Se content of sow milk declined with parity but was not affected by dietary vitamin E level. Sow liver tocopherol at weaning (28 d postpartum) increased (P less than .01) as dietary vitamin E increased and increased with parity (P less than .05). Pig serum and liver alpha-tocopherol concentrations were elevated at birth and 7 and 28 d of age as sow dietary level of vitamin E increased. Upon weaning, pigs were fed a torula yeast-dextrose diet that contained 3.0 mg of alpha-tocopherol/kg and .32 ppm Se for a 28-d postweaning period. Liver and serum alpha-tocopherol concentrations declined during the postweaning period. Evidence of the vitamin E deficiency occurred at 28 d postweaning in the progeny from sows fed the basal diet or 16 IU of vitamin E; the incidence was more prevalent in the pigs from Parities II and III. These results suggest that a supplemental level of 16 IU of vitamin E/kg of diet was inadequate for the reproducing sow; higher levels are justified, particularly when females are retained in the herd for several parities. PMID- 1885401 TI - Nutritional and toxicological evaluations of kochia hay (Kochia scoparia) fed to lambs. AB - Kochia foliage that had tested positive to Dragendorff's reagent (presumptive alkaloids) and had elicited chronic toxicosis when fed to rats was fed to sheep to characterize early stages of kochia toxicosis and evaluate treatments that might improve tolerance. Twelve fine-wool lambs (46 +/- 9 kg BW) were fed chopped kochia hay (35%) mixed with chopped alfalfa hay (65%) for 4 wk. The kochia diet had 14.3% CP and 39.9% ADF. Dry matter intake averaged 3.4% of BW/d. Body weight did not change during 4 wk and blood serum components were not changed from values at the onset. Thereafter, kochia was increased to 50% of diet for five more weeks, during which four treatments were imposed randomly (three lambs/treatment): 1) none; 2) N-acetyl-L-cysteine plus trans-stilbene oxide, 21 and 52 mg/kg of BW, respectively, given i.p. twice weekly; 3) retinyl palmitate, 275 mg, plus alpha-tocopherol, 300 mg/lamb dosed i.m. twice weekly; and 4) zinc sulfate mixed in the feed to provide 500 mg daily. Kochia contained 4.8% oxalate. The diet with 50% kochia had 16% CP and 36% ADF, and digestibility coefficients were 59% for DM, 72% for CP, and 59% for ADF. After 5 wk, blood glucose was elevated slightly, total bilirubin was increased about 1.5-fold (P less than .05), alanine aminotransferase was elevated slightly (P less than .05), and inorganic phosphorus and urea (blood urea N) were diminished (P less than .05); other serum components, including calcium, were unchanged from initial levels (P greater than .10). Treatments had negligible effects for modifying serum signs of mild chronic toxicosis associated with kochia hay fed as 50% of diet. PMID- 1885402 TI - Altered metabolic hormones, impaired nitrogen retention, and hepatotoxicosis in lambs fed Kochia scoparia hay. AB - Livestock grazing lush Kochia scoparia (L.) Schrad, sometimes experience BW loss, hyperbilirubinemia, photosensitization, and polyuria. Animals fed kochia hay may exhibit milder or negligible signs of toxicosis but fail to utilize nutrients efficiently. To characterize early aspects of kochia toxicosis and to evaluate prospective treatments, 12 wether lambs (34 +/- 3 kg) were fed prebloom kochia hay (83% OM, 15% CP, and 6.3% total oxalate) and treated as follows: 1) no treatment; 2) drenched daily with aqueous ZnSO4 to provide 30 mg of Zn/kg of BW); 3) injected i.p. twice weekly with N-acetyl-L-cysteine (CYS) in saline (21 mg/kg of BW) plus trans-stilbene oxide (TSO) in corn oil (27 mg/kg of BW); and 4) treated as 2) plus 3). Treatments were imposed factorially (2 x 2) with three lambs per treatment. Kochia intake (ad libitum) averaged .57 kg/d (1.7% of BW) for 80 d, and digestibility of DM and CP were 44 and 59%, respectively, at wk 4, but BW loss was severe (6 to 11 kg/lamb). After 14 d, serum insulin and prolactin were decreased (P less than .05) below initial values (.48 to .11 and 102 to 28 ng/ml, respectively). Serum somatotropin increased (P less than .05) from 4.5 to 6.8 ng/ml at 4 wk. Serum total bilirubin increased threefold at 3 wk (P less than .05) and declined slightly thereafter through 10 wk. Early changes in serum enzymes reflected mild hepatotoxicosis without cholestasis, whereas histopathology (at 80 d) showed diffuse hepatocyte swelling and nephrosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1885403 TI - Serum constituents and metabolic hormones in sheep and cattle fed Kochia scoparia hay. AB - Kochia scoparia (L.) Schrad. is a prospective forage crop for arid areas, although its potential value is constrained by occasional toxicity that may involve alteration of metabolic hormones. The present research compared serum clinical profiles and metabolic hormone concentrations in steers and wethers fed kochia hay (85% OM, 13% CP, 45% ADF, and 6.3% total oxalate) to those of suitable controls that were pair-fed equal amounts of DM as alfalfa hay (91% OM, 13% CP and 42% ADF). Eight steers (240 +/- 2 kg BW) that were pair-fed kochia or alfalfa hay for 21 d had similar levels of serum insulin (INS) or somatotropin (GH), but kochia lowered prolactin (PRL) (6.0 vs 118 ng/ml; P = .14). Kochia hay did not elevate serum bilirubin at d 21 in these steers; however, lactic dehydrogenase and aspartate aminotransferase activities were elevated 1.3-fold (P less than .05). Ten fine-wool wethers (29 +/- kg BW) pair-fed kochia or alfalfa hay for 21 d had similar levels of PRL and INS at d 0, 5, 10, and 21; however, GH was lower in wethers fed kochia at d 5 (P less than .05) and somewhat lower at d 10 and 21. Kochia elevated serum unconjugated bilirubin 1.25-fold over pair-fed controls (P = .06) and increased (P less than .05) activities of aspartate and alanine aminotransferases. Metabolic hormone responses to kochia hay differed in steers vs wethers during undemutrition and mild toxicosis that occurred within 3 wk. PMID- 1885404 TI - The influence of disease on feed and water consumption and on pharmacokinetics of orally administered oxytetracycline in pigs. AB - In the present study the feed and water consumption and pharmacokinetic parameters of orally administered oxytetracycline were compared in clinically healthy pigs and in the same pigs following a challenge with Actinobacillus (Haemophilus) pleuropneumoniae toxins. Endobronchial challenge with A. pleuropneumniae toxins was accompanied by anorexia, increased lassitude, labored breathing, fever, and increased white blood cell counts. Pleuropneumonia was evident in all pigs on autopsy. Following the challenge, both feed and water consumption were markedly reduced. In contrast to recommendations in the literature, it is concluded that drugs should not be administered to pneumonic pigs via water. In healthy pigs the oral bioavailability of oxytetracycline (50 mg/kg), given on an empty stomach, was 4.8% and the elimination half-life (t1/2 beta) was 5.92 h. After challenge, the pigs showed great variation in oxytetracycline plasma concentrations. In addition, the mean computed elimination rate constant (beta), t1/2 beta, the area under the plasma concentration-time curve (AUC), and clearance in pneumonic pigs differed significantly (P less than .05) from the values found in healthy pigs. The elimination half-life (t1/2 beta), AUC, and volume of distribution (Vd area) were increased. In diseased pigs the mean of maximum plasma concentrations (.87 micrograms/ml) was reached after 7 h, in contrast to 1.74 h (1.87 micrograms/ml) in the healthy pigs. PMID- 1885405 TI - Safety of L-tryptophan for pigs. AB - Epidemic eosinophilia-myalgia syndrome (EMS) associated with excess L-tryptophan (Trp) consumption in humans has been declared a major public health problem. The EMS problem has not been observed in pigs, nor has comprehensive pathology associated with EMS in humans been described. Experiments were therefore conducted to evaluate the pathology and effects of excess dietary L-Trp for finishing (79 to 119 kg) pigs and to determine an LD50 of Trp for pigs. In Exp. 1, addition of .1 or 1% Trp to corn-soybean meal diets had no effect on growth performance or leukocyte and relative eosinophil counts or on plasma aspartate transferase, creatine phosphokinase, and lactate dehydrogenase activities. Likewise, untoward pathological effects of Trp feeding were not observed in the animals under study. In Exp. 2, supplementing the basal diet with 0, 2, and 4% Trp caused linear (P less than .05) decreases in weight gain, feed intake, and gain:feed ratio. Mortality could not be produced by acute oral dosing in the LD50 study (Exp. 3), wherein Trp doses between 2.00 and 5.71 g/kg of BW were administered by stomach tube. Vomiting occurred at oral doses greater than 5.71 g/kg of BW. These results suggest that oral ingestion of Trp in pigs is safe and that pigs can tolerate considerable excesses of Trp. PMID- 1885406 TI - Effects of recombinant porcine somatotropin on metabolic rate in growing pigs. AB - Effects of recombinant porcine somatotropin (rpST) on metabolic rate were studied in two trials with 24 crossbred barrows (Yorkshire x Landrace) in each. The barrows weighed about 80 kg (SE within trials 2.2 kg) at the start of the measurements and in each trial 12 pigs received 4 mg of rpST and 12 received a placebo. The diet contained 2.57 Mcal NE/kg and 20% CP (about 1% lysine). Animals were fed approximately 2.8 times maintenance (280 kcal ME.kg-.75.d-1). Heat production (gaseous exchange of CO2 and O2) and activity were measured continuously. Heat production associated with activity was calculated from the regression of heat production on activity. Animals treated with rpST exceeded controls in rate of gain by 252 g/d (P less than .001) and in metabolic rate by 14.5 kcal.kg-.75.d-1 (P less than .01). The rpST treatment increased rectal (+ .2 degrees C) and surface (+ .8 degrees C) temperatures. Activity-related heat production in treated pigs was increased, but this was only partly related to the increase in metabolic rate with rpST. The daily patterns of total and activity related heat production were similar between pigs in both experimental treatments. PMID- 1885407 TI - Catheterization of the caudal vena cava via the lateral saphenous vein in the ewe, cow, and gilt: an alternative to utero-ovarian and medial coccygeal vein catheters. AB - Current methods for obtaining venous blood from the reproductive organs of livestock often have a low rate of success or involve intensive surgical procedures that may impair ovarian function. Therefore, the caudal vena cava was catheterized via the lateral saphenous vein to determine the feasibility of using this method for chronic sampling of blood draining from the reproductive organs of ewes (n = 6), cows (n = 6), and gilts (n = 7). Blood samples were collected at 2-cm (ewes and gilts) or 5-cm (cows) intervals during insertion of catheters. Correct placement, defined as the position at which plasma concentrations of progesterone or estrogen were at least threefold greater than in jugular venous plasma, varied among species and among animals within species. It seemed, however, that a majority of catheters would be placed correctly if secured at 48 to 52 cm in ewes, 52 cm in gilts, and 90 to 100 cm in cows. Saphenous vein catheters were secured for sequential sampling of vena caval blood during the follicular phase of ewes (n = 25), cows (n = 4), and gilts (n = 5). Catheters remained patent for the duration of sampling in all individuals. Concentrations of estrogen in jugular and vena caval plasma were correlated (ewe P less than .0003; cow P less than .0001; gilt P less than .0001). Profiles of progesterone and estrogen revealed an episodic pattern of secretion in vena caval but not jugular plasma. Catheterization of the vena cava via the saphenous vein is a relatively simple and noninvasive method for obtaining blood containing uterine and ovarian hormones before their metabolism. PMID- 1885409 TI - Disruption of estrous behavior in ewes by dexamethasone or management-related stress. AB - The effect of dexamethasone administration, isolation stress, or transportation stress on the ability of exogenous estradiol to induce estrus in progesterone primed, ovariectomized ewes was evaluated in this study. Dexamethasone administered twice daily over a 6-d period, or a single injection at either 2 h before estradiol administration or 8 h after estradiol treatment, delayed or blocked the expression of estrous behavior. In those animals in which dexamethasone did not block the onset of estrus, the average length of estrus was reduced. Isolation stress, which induced significant increases in the plasma concentration of corticosteroids, failed to significantly alter the number of ewes expressing estrous behavior, although the expression of estrus was blocked in three of the nine treated animals. These nine animals all expressed estrus during the nonstress phase. In contrast to isolation stress, 8 h of transportation not only increased the average plasma concentration of corticosteroids, but also significantly (P less than .05) blocked the expression of estrus in five of eight ewes and delayed the expression of estrus in one other. During the nonstressed control phase, all eight expressed estrus. These findings indicate that management-related stress can block estrogen from inducing estrous behavior, however, the role of the adrenal axis response to stress in blocking estrus remains to be clarified. PMID- 1885408 TI - Effect of constant versus adjusted dose of exogenous porcine growth hormone (pGH) on growth and reproductive characteristics of gilts. AB - Growth, carcass traits, and selected reproductive characteristics were evaluated in prepubertal gilts treated with either a constant mass of pGH or a mass of pGH adjusted periodically for changes in BW. Gilts (64 kg, n = 24) were given 24 daily injections of either vehicle (C; control) or one of two doses of pGH: 70 micrograms/kg of BW, with dose adjusted every 5th d for changes in BW (A; adjusted), or 70 micrograms/kg of initial BW (U; unadjusted). Gilts were slaughtered on d 25. Gilts treated with pGH had higher ADG (P less than .002) and improved feed efficiency (kg of feed/kg of gain; P = .0003) compared with controls. Weights of adrenal glands, liver, heart, and kidney were higher (all P less than .01) for Groups A and U than for Group C gilts. Average backfat thickness was less (P less than .004) for A and U gilts than for C gilts and less for Group A than for Group U (P less than .02). Furthermore, growth and carcass traits were similar (P greater than .05) for Groups A and U, except for measurements of first rib backfat, last rib backfat, and average backfat depth (P less than .05). Culture of granulosa cells (GC) was employed to assess ovarian function. Addition of FSH to the culture media enhanced secretion of progesterone (P4) by cultured GC from all in vivo treatments compared with unsupplemented cultures of GC (P less than .05). Addition of LH to the culture media enhanced secretion of P4 by cultured GC from pGH-treated gilts only (P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1885410 TI - Pig endometrial cells in primary culture: morphology, secretion of prostaglandins and proteins, and effects of pregnancy. AB - Luminal epithelial, glandular epithelial, and stromal cells were isolated from pig endometrium by enzymatic dispersion and sieve filtration. The three cell types, maintained in primary culture, showed distinctly different morphologies when viewed by light and scanning electron microscopy. Immunocytochemical staining indicated that luminal and glandular epithelial cells were positive for both cytokeratin and vimentin. However, stromal cells were positive only for vimentin. Acid phosphatase activity was detected in the culture medium of glandular cells and increased (P less than .05) when progesterone (.1 microM) was included in the culture medium. The secretion of uteroferrin by glandular cells was also indicated by one-dimensional PAGE and Western blot analysis. Stromal cells produced more (P less than .01) prostaglandin E (PGE) than prostaglandin F2 alpha (PGF2 alpha), whereas glandular cells secreted more (P less than .01) PGF2 alpha than PGE. Pregnancy status affected prostaglandin secretion in that stromal cells secreted less (P less than .01) PGE and PGF2 alpha and glandular cells secreted less (P less than .05) PGF2 alpha when they were harvested from pregnant vs cyclic pigs. Furthermore, the PGE:PGF2 alpha ratio in medium from stromal cells was greater (P less than .01) for cells collected from pregnant pigs. This culture system provides an in vitro model for studying the hormonal regulation of the endometrium and potentially may be useful for studying interactions between endometrial cells and embryos in the pig. PMID- 1885411 TI - Effects of the inclusion of yeast culture (Saccharomyces cerevisiae plus growth medium) in the diet of dairy cows on milk yield and forage degradation and fermentation patterns in the rumen of steers. AB - The effects of including yeast culture (YC; Saccharomyces cerevisae plus growth medium; 5 x 10(9) organisms/g) in diets for ruminants was examined in two experiments. In Exp. 1, 32 multiparous Friesian dairy cows were fed between wk 7 to 12 of lactation one of four completely mixed diets based on either hay or straw plus rolled barley (mixed to give concentrate:forage ratios of either 50:50 or 60:40, respectively) with or without 10 g YC/d in a 2(3) factorial design. Supplementation with YC increased DM intake of the cows by a mean of 1.2 kg/d (P less than or equal to .062) and increased milk yield by 1.4 liters/d (corrected to 4% butterfat; P less than or equal to .05). There was an interaction (P less than .05) between diet composition and YC addition; effects of YC were greatest in diets containing 60:40 (concentrate:forage) ratio. In Exp. 2, three steers were fed a diet of 50% hay and 50% rolled barley (DM basis). Hay was available for the major part of the day but barley was fed in two meals/d. Addition of YC to the diet increased (P less than .05) ruminal pH for 4 h after the barley meal. This elevation in pH probably was due to a reduction (P less than or equal to .01) in the concentration of L-lactate in the ruminal liquor of steers given YC (1.43 vs 3.55 mM; P less than or equal to .01). Peak ruminal L-lactate concentration (7.75 mM) in the controls coincided with time of minimum pH values (2 h after the meal of barley); this peak was absent in steers given YC. YC had no effect on the concentration of VFA in ruminal liquor, but the ratio of acetate to propionate was reduced (P less than or equal to .01) from 3.3:1 to 2.8:1 in steers given YC. The extent of DM degradation of hay incubated in the rumen of steers fed the hay and rolled barley diet was increased (P less than .05) in the presence of YC at 12 h of incubation, but degradation was similar in all treatment groups after 24 h of incubation. Presence of yeast culture in the rumen had effects on ruminal stoichiometry. An increased rate of forage degradation may have increased forage intake and productivity of these dairy cows. PMID- 1885412 TI - Selection of a sterilization method for the study of cereal grain digestion. AB - Experiments were initiated to select a sterilization method(s) that minimizes alterations in the digestive properties of cereal grains and, thus, would be suitable for the study of cereal grain digestion by pure cultures of ruminal bacteria. The following five treatments were examined: unsterilized (U), autoclaving with buffer (AB), autoclaving without buffer (AD), ethylene oxide (E), and gamma irradiation (I). Solubility of DM, starch, and CP was determined by soaking grain in buffer for 1 h followed by filtration through Whatman #54 filter paper. Ground corn and wheat from each treatment were placed in vials with a 1:1 mixture of Bryant's medium and ruminal inoculum. Vials were incubated for 4, 8, 12, 24, and 48 h and analyzed for starch content. Bacterial growth was not evident in sterilized, uninoculated samples. The AD treatment decreased the disappearance of CP in wheat and corn, whereas AB caused an increase in the disappearance of DM, CP, and starch in wheat (P less than .001) compared with U. Rates of microbial starch digestion for corn were 1.3, 1.5, 3.3, 14.7, and 3.5%/h and for wheat were 1.3, 3.4, 4.6, 17.1, and 4.6%/h for AD, E, I, AB, and U, respectively. Contrasts indicated that AD and AB differed (P less than .001) from U for both corn and wheat. It is likely that gelatinization of cereal starch enhanced microbial starch digestion in AB and the formation of Maillard products reduced starch digestion in AD. Corn and wheat sterilized with E or I had digestive properties that closely resembled those of U grain, and either sterilization method was suitable for studying cereal grain digestion. PMID- 1885413 TI - Evaluation of wheat middlings as a supplement for beef cattle consuming dormant bluestem-range forage. AB - Two experiments were conducted to evaluate wheat middlings as a supplement for cattle consuming dormant bluestem-range forage. Effects of supplement type and amount were evaluated in Exp. 1, which consisted of feeding supplements of soybean meal:grain sorghum (22:78) or two different amounts of wheat middlings. Sixteen ruminally fistulated steers were blocked by weight (BW = 374 +/- 8.3 kg) and assigned randomly to the following treatments: 1) control, no supplement (NS); 2) soybean meal:grain sorghum (SBM/GS) formulated to contain the same CP concentration (21%) and fed to provide a similar energy level (3.5 Mcal of ME/d); 3) a supplement of 100% wheat middlings fed at a low level (LWM); and 4) 100% wheat middlings fed at twice the amount of LWM (7 Mcal of ME/d; HWM). The influence of different supplemental CP concentrations in a wheat middlings-based supplement was evaluated in Exp. 2. Sixteen ruminally fistulated steers were blocked by weight (BW = 422 +/- 8.1 kg) and assigned randomly to the following treatments: 1) control, no supplement (NS); 2) 15% CP; 3) 20% CP; and 4) 25% CP supplements. These supplements consisted of 60% wheat middlings and various ratios of soybean meal and grain sorghum to achieve the desired CP concentration. In Exp. 1, SBM/GS and HWM supplements increased (P less than .10) and LWM tended to increase (P = .16) forage DMI compared with NS. All supplements in Exp. 1 increased (P less than .10) DM digestibility, ruminal DM fill, and ruminal indigestible ADF (IADF) passage rate compared with NS, although the greatest response in fill and passage was observed with HWM. In Exp. 2, forage DMI, DM digestibility, NDF digestibility, ruminal DM and IADF fill, IADF passage rate, and fluid dilution rate were increased (P less than .01) by supplementation. Forage DMI, ruminal IADF passage rate, and fluid dilution rate increased quadratically (P less than .10), and NDF digestibility, ruminal DM and IADF fill increased linearly (P less than .10) with increased supplemental CP concentration. These experiments indicate that wheat middlings performed similarly to a SBM/GS supplement of equal CP concentration, when both were fed to provide a similar amount of energy daily. Additionally, use of poor-quality range forage was enhanced when wheat middlings-based supplements were formulated to contain a CP concentration of 20% or greater. PMID- 1885414 TI - Effect of coliform bacteria, feed deprivation, and pH on ruminal D-lactic acid production by steer or continuous-culture microbial populations changed from forage to concentrates. AB - Fecal coliform bacteria were isolated from three herbivores (cattle, horse, and red panda) and shown to produce primarily the D-form of lactate, plus acetate and ethanol when grown anaerobically in 1.0% glucose broth. To evaluate coliform contribution to D-lactate acidosis in cattle, experiments involving a forage adapted steer (fasted or normally fed) and four 500-ml fermentors were compared during 3 d of grain overload. In both systems, coliforms and D- and L-lactic acid production were greater from fasted than from normally fed steer inoculum. With fasted inoculum, coliform counts peaked (3 x 10(7)/ml at 7 h after initial engorgement) and receded to 10(3)/ml by the time D-lactate concentration peaked, indicating that bacteria other than coliform were responsible for the delayed peaking of D- (48 h) compared with L-lactate (24 h). Increases in lactobacilli more closely mimicked D-lactate increases than did changes in coliforms. The comparisons between the steer and fermentors showed many similar shifts in end products and groups of bacteria, more so with the experiment initiated with fasted than with normal inoculum. With normal inoculum, VFA content and moles of butyrate/100 mol of VFA were greater in vitro than in vivo; VFA content presumably was larger because of VFA absorption in vivo. In a separate experiment, cultures initiated with identical inoculum and given the same amount of feed accumulated more lactate when pH was permitted to decrease to 5.0 than when pH was maintained at 5.5 for 6.0 or above, indicating the role buffers can have in controlling acidosis during diet change to concentrates. PMID- 1885415 TI - Snore therapy in dentistry. PMID- 1885416 TI - Extrapolating to bacterial life outside the test tube. PMID- 1885417 TI - Antibacterial activity of lomefloxacin. AB - Lomefloxacin has marked activity against Gram-negative bacilli including Enterobacteriaceae, non-fermenting strains and Haemophilus influenzae with 98% of all isolates tested having MICs of 0.25 mg/l or less. Sixty-eight per cent of Pseudomonas aeruginosa strains were sensitive to 1 mg/l with a few strains resistant to 8 or 16 mg/l. Gram-positive cocci were more resistant, particularly streptococci, where the MICs vary between 1 and 8 mg/l. Bactericidal activity was similar to inhibitory activity and the effect of increasing serum concentrations and bacterial inocula was minimal. The MIC and MBC were increased in the presence of urine, particularly at an acid pH 5. Comparative MICs showed that lomefloxacin was more active than ofloxacin and pefloxacin, similar to norfloxacin but less active than ciprofloxacin for Gram-negative bacteria but not for Gram-positive cocci. Comparative studies with sensitivity disc concentrations showed that a 5 micrograms disc was more satisfactory than the 10 micrograms disc as the zone sizes were more suitable for routine testing. Solutions of lomefloxacin showed instability in bright sunlight when 52% of activity was lost in 1 h. Similar instability was shown in impregnated discs which lost up to 40% activity in 6 h exposure. Lomefloxacin showed a wide range of activity against Gram-negative bacteria including multiresistant strains and Pseudomonas spp. Gram-positive bacteria were less susceptible, with streptococci more resistant than staphylococci. Lomefloxacin is well absorbed after oral administration giving high blood and urine concentrations and its prolonged half-life means once daily dosing in the treatment of many types of bacterial infection may be possible. PMID- 1885418 TI - Meropenem: in-vitro activity and kinetics of activity against organisms of the Bacteroides fragilis group. AB - Meropenem was compared with imipenem and nine other antimicrobial agents, against 101 strains of the Bacteroides fragilis group. Meropenem was active against all strains tested, and its activity was similar to, and in many cases better than, that of imipenem. The activity of meropenem was similar to that of metronidazole, and greater than that of the other antimicrobial agents tested. The bactericidal activity of meropenem against B. fragilis was impressive, since the MBC to MIC ratios were no greater than two. The bactericidal activity was confirmed by time killing curve assays with two strains which showed that meropenem was rapidly bactericidal and reduced the initial inoculum significantly during the first 4-6 h. The postantibiotic effect of meropenem (2-4 h) and a sub-inhibitory concentration of 1/4 x MIC suggested that meropenem interferes with the normal growth of B. fragilis, even when administered concentrations fall below the MIC. MICs of meropenem were affected minimally by the pH of the medium or by an increase in inoculum size. Meropenem continued to have good activity against a B. fragilis strain that had been induced for the production of cephalosporinase. The in-vitro data presented in this paper indicate that meropenem is a promising antimicrobial agent which may be useful in the treatment of problematic mixed infections. PMID- 1885419 TI - The effects of minocycline and tetracycline on the mitotic response of human peripheral blood-lymphocytes. AB - The effects of minocycline and tetracycline on the mitotic response of human peripheral blood lymphocytes was investigated in vitro. The effects of the antibiotics on the mitotic response of purified lymphocytes stimulated with Interleukin-1 beta varied according to the individual from whom the lymphocytes were obtained. At concentrations above those reported to be present in serum during conventional therapy (2-8 mg/l), there was a tendency for both minocycline and tetracycline to suppress the mitotic response. Minocycline was superior to tetracycline in this respect. However, at physiological concentrations the antibiotics either had no significant effect, suppressed the mitotic response (minocycline at 2 mg/l with one of six donors), or enhanced the mitotic response (tetracycline at 2 and 8 mg/l with four of six donors). The stimulatory effect of tetracycline was not demonstrated when lymphocytes were cultured in whole blood for up to seven days with the antibiotic alone. Similar effects of the antibiotics were observed when mononuclear cell fractions isolated from six donors were stimulated with an optimal concentration of phytohaemagglutinin (PHA). Stimulation of lymphocytes in whole blood cultures with PHA in the presence of minocycline and tetracycline revealed that, under these culture conditions, the antibiotics could suppress the mitotic response of lymphocytes at physiological doses with cells from a majority of donors. PMID- 1885420 TI - Comparative activities of amoxycillin, amoxycillin/clavulanic acid and tetracycline against Chlamydia trachomatis in cell culture and in an experimental mouse pneumonitis. AB - The activity of amoxycillin, amoxycillin/clavulanic acid and two tetracycline antibiotics was investigated against three strains of Chlamydia trachomatis in vitro. McCoy cells were infected and single doses of antibiotic administered 24 h after infection. The percentage of infected cells was calculated at intervals up to 72 h after infection. Amoxycillin and clavulanic acid, alone and in combination, reduced the incidence of inclusion formation of all three strains. Particularly good activity was observed against the laboratory-adapted strain C. trachomatis Sa2f and a clinical isolate C. trachomatis LB1, where a progressive reduction in numbers of inclusions was observed with time. Minocycline and oxytetracycline were the most active agents tested. In an experimental animal model, mice were inoculated intranasally with C. trachomatis MoPn (ATCC VR123) which caused a fatal pneumonia within 16 days, and treated orally for four days commencing at 24 h after infection. At doses producing clinically achievable serum concentrations, amoxycillin (10 mg/kg), amoxycillin/clavulanic acid (10 + 5 mg/kg) and minocycline (5 mg/kg) all protected the mice over a 21-day period. The majority of the animals treated with clavulanic acid alone (20 mg/kg) survived the infection. Treatment with oxytetracycline was less effective, a dose of 160 mg/kg being required to protect 70% of the mice. The results indicate that amoxycillin and amoxycillin/clavulanic acid were more effective against C. trachomatis MoPn in vivo than might be predicted from in-vitro data, suggesting that amoxycillin/clavulanic acid may have potential for the treatment of polymicrobial infections involving C. trachomatis. PMID- 1885421 TI - Activity of minocycline against Toxoplasma gondii infection in mice. AB - The chemotherapeutic activity of minocycline, a semi-synthetic tetracycline analogue, was evaluated in a murine model of toxoplasmosis. A lethal acute toxoplasmosis was produced by injecting 10(5) tachyzoites of the RH strain of Toxoplasma gondii into the peritoneal cavities of Swiss-Webster mice. When infected mice were treated once daily for 12 days, starting 2 h after challenge, the survival and cure rates were 100% and 40% respectively after minocycline alone (100 mg/kg per day), 0% and 0% after pyrimethamine alone (8.5 mg/kg per day), and 100% and 50% after combination of the two drugs at the same dosages. Absolute survival and cure with minocycline were observed when mice were treated with two daily doses of 100 mg/kg for 12 days. Mice chronically infected with a low virulent strain of T. gondii (Me49) showed a significant reduction in the number of brain cysts after three weeks of treatment with 50 mg/kg per day of minocycline. Minocycline serum levels after a single oral administration of 50 mg/kg or 100 mg/kg to normal mice, peaked at 1.8 mg/l and 10 mg/l after 1 h, respectively, and showed an extended half-life. PMID- 1885422 TI - Reappraisal of amoxycillin absorption kinetics. AB - Interest in the intestinal absorption mechanisms of drugs has increased because transepithelial passage across the gut does not necessarily follow a passive diffusion process. Amoxycillin, like other amino-beta-lactam antibiotics, has been demonstrated in vitro to use the dipeptide carrier-mediated system in rodent small intestine. In order to assess the in-vivo relevance of these data, we applied the Loo-Riegelman method for a reappraisal of amoxycillin absorption kinetics in healthy human volunteers. The results showed evidence of a saturable carrier-mediated uptake of this antibiotic. With respect to the in-vitro data previously published, the dipeptide carrier system would appear to be the most likely transport mechanism. PMID- 1885423 TI - Pharmacokinetic study of lomefloxacin and its effect on the faecal flora of volunteers. AB - In a volunteer pharmacokinetic study mean peak serum concentrations of lomefloxacin of 7.19 mg/l were obtained 1.5 h after an oral dose of 400 mg. Women had higher concentrations than men. Urinary excretion was 34% in 6 h and 63% in 24 h and the mean peak concentration was 699 mg/l. Saliva concentrations were 37% of those in serum. Lomefloxacin was detectable in the faeces up to seven days after the last dose. The major effect of lomefloxacin on the faecal flora of volunteers following a four day course of 400 mg once daily was the elimination of strains of Enterobacteriaceae and an increase in the numbers of Gram-positive cocci, mainly streptococci. There was no effect on anaerobic bacteria or yeasts. Lomefloxacin was well tolerated and no side effects were recorded. No bacterial resistance was detected after treatment. PMID- 1885425 TI - Clinical evaluation of ticarcillin, with clavulanic acid, and gentamicin in the treatment of febrile episodes in neutropenic children. AB - To assess the clinical efficacy of ticarcillin, with clavulanic acid, and gentamicin, we conducted a prospective one year study of febrile episodes in neutropenic children. Seventy-five episodes were evaluated in 42 children. The response rate was 32% during persistent neutropenia, whilst another third of episodes responded with neutrophil recovery. Positive blood cultures occurred in 21 episodes and 20 of 24 micro-organisms belonged to the 'community' flora, i.e. organisms carried by healthy people (Streptococcus pneumoniae, Staphylococcus aureus, Branhamella catarrhalis and Escherichia coli). The route of pathogenesis was endogenous in 76% of the patients. There was a substantial superinfection related morbidity (14%) and mortality (7%), related to emergence of resistance during and after parenteral antibiotic administration. The poor clinical response, combined with emergence of resistance, lead to the conclusion that this combination is of limited value as a first line regimen for neutropenic patients. PMID- 1885424 TI - The pharmacokinetics of cefuroxime axetil in the sick elderly patient. AB - The pharmacokinetics of cefuroxime axetil (RS3 formulation) were studied in 20 elderly patients following admission for lower respiratory or urinary tract infection. The mean age was 83.9 years. A 12-hourly dose of 250 mg was given for five days. The mean time to attain maximum serum concentration was 3.2 h with a mean peak concentration of 8.5 mg/l. The mean serum elimination half-life was 3.5 h and the AUC0-infinity 60.4 mg/h.l. There was no accumulation of the drug in the patients studied after five days treatment. The data suggest that the standard dosage regimen is adequate in the sick elderly patient. PMID- 1885427 TI - Ciprofloxacin and CAPD peritonitis. PMID- 1885426 TI - Episodic acyclovir therapy to abort recurrent attacks of genital herpes simplex infection. AB - Frequent recurrence of genital herpes simplex infection can be a distressing condition. Continuous suppressive oral acyclovir is effective but expensive. Hitherto episodic therapy has given disappointing results. An open comparative study of patient initiated therapy is reported here. Acyclovir 200 mg five times daily for five days aborted 44% of recurrences and shortened 38% by greater than or equal to 50%, giving useful response in 82% of 34 recurrences. Acyclovir 400 mg twice daily for five days aborted 60% and shortened 17% giving useful benefit in 77% of 20 recurrences. Acyclovir 200 mg twice a day for five days gave unsatisfactory results. Patients were selected for frequent recurrences and a recognized prodrome, and care was taken to help to identify early prodromal symptoms. In these patients acyclovir in dosages of 200 mg five times daily for five days and 400 mg bd for five days proved convenient and cost effective. PMID- 1885428 TI - Plasmid mediated ceftazidime resistance identified in a strain of Serratia marcescens isolated in Belgium. PMID- 1885429 TI - Beta-lactamase production in human and animal isolates of Campylobacter jejuni in Turkey. PMID- 1885431 TI - Action of intercostal muscles on the lung in dogs. AB - The action on the lung of interosseous intercostal muscles located in the third and the seventh interspaces was studied in 15 anesthetized-curarized supine dogs. Changes in pleural pressure, airflow rate, and lung volume produced by maximal stimulation of both intercostal muscle layers were measured at and above functional residual capacity (FRC). In five animals measurements were also obtained during isolated stimulation of the internal layer. At FRC, intercostal stimulation in the upper interspaces had invariably an inspiratory effect on the lung but no effect was detectable in the lower interspaces. Qualitatively similar results were obtained during isolated stimulation of the internal layer. Increasing lung volume reduced the inspiratory action of the upper intercostals and conferred an expiratory action to the lower intercostals. These results indicate the following: 1) when contracting in a single interspace, the external and internal intercostals have a qualitatively similar action on the lung; and 2) this action, however, depends critically on their location along the cephalocaudal axis of the rib cage: in the upper portion of the rib cage, both muscle layers have an inspiratory effect at and above FRC; in the lower portion of the rib cage, they have no respiratory action at FRC and act in the expiratory direction at higher lung volumes. PMID- 1885430 TI - Applications of fractal analysis to physiology. AB - This review describes approaches to the analysis of fractal properties of physiological observations. Fractals are useful to describe the natural irregularity of physiological systems because their irregularity is not truly random and can be demonstrated to have spatial or temporal correlation. The concepts of fractal analysis are introduced from intuitive, visual, and mathematical perspectives. The regional heterogeneities of pulmonary and myocardial flows are discussed as applications of spatial fractal analysis, and methods for estimating a fractal dimension from physiological data are presented. Although the methods used for fractal analyses of physiological data are still under development and will require additional validation, they appear to have great potential for the study of physiology at scales of resolution ranging from the microcirculation to the intact organism. PMID- 1885432 TI - Hypoxia-mediated in vivo release of dopamine in nucleus tractus solitarii of rabbits. AB - A wide variety of neuroactive substances have been suggested to be involved in the respiratory depression observed in response to severe hypoxia. By use of the technique of microdialysis, the release of dopamine (DA) was measured in the nucleus tractus solitarii during severe hypoxic provocations (6% O2 in N2) in the adult pentobarbital-anesthetized rabbit. DA release was analyzed by high performance liquid chromatography with electrochemical detection. Such hypoxic provocations caused pronounced phase of depression in the phrenic nerve activity and enhanced release of DA. After bilateral carotid sinus nerve denervation, acute severe hypoxia did not give rise to enhanced release of DA or to phrenic nerve depression. Mild hypoxic (9% or 12% O2 in N2) or hypercapnic (6% CO2) stimuli resulted in an increased phrenic nerve activity without any concomitant changes in DA release. Decerebration at the midcollicular level in rabbits prevented an enhanced release of DA in the nucleus tractus solitarii during severe hypoxia. The results suggest that 1) DA is involved in the central ventilatory response to severe hypoxia, 2) not only the initial excitatory but also the second depressive phase in response to severe hypoxia is mediated partially by the peripheral chemoreceptors, and 3) the depressive phase is dependent on intact connections from suprapontine structures. PMID- 1885434 TI - Thyroarytenoid muscle activity during loaded and nonloaded breathing in adult humans. AB - Previous fiber-optic studies in humans have demonstrated narrowing of the glottic aperture in expiration during application of expiratory resistive loads. Nine healthy subjects were studied to determine the effect of expiratory resistive loads on the electromyographic activity of the thyroarytenoid (TA) muscle, a vocal cord adductor. Four of the nine subjects also underwent the application of inspiratory resistive loads and voluntary prolongation of either inspiratory (TI) or expiratory (TE) time. TA activity was recorded by intramuscular hooked-wire electrodes. During quiet breathing in all subjects, the TA was phasically active on expiration and often tonically active throughout the respiratory cycle. TA expiratory activity progressively increased with increasing levels of expiratory load. Inspiratory loads resulted in increased TA "inspiratory" activity. Voluntary prolongation of TE to times similar to those reached during loaded breathing induced increases in TA expiratory activity similar to those reached during the loaded state. Voluntary prolongation of TI was associated with an increase in TA inspiratory activity. Similar increases in TI during inspiratory loading or voluntary conditions were associated with comparable increases in TA inspiratory activity in three of the four subjects. In conclusion, increased activation of TA during the application of expiratory resistive loads implies that the reported narrowing of glottic aperture during expiratory loading is an active phenomenon. Changes in activation of the TA with resistive loads appear to be related to changes in respiratory pattern. PMID- 1885433 TI - Effect of atelectasis and surface tension on pulmonary vascular compliance. AB - The effects of atelectasis and surface tension on the vascular volume and compliance in an isolated perfused dog lung lobe were studied using vascular occlusion and indicator-dilution methods. Measurements were made during atelectasis and again after the lobes were inflated with either a gas mixture (air) or 0.9% saline. Inflation with air resulted in a 20% increase in vascular volume (P less than 0.02), whereas saline inflation had no effect on vascular volume. Inflation with either air or saline increased static vascular compliance by approximately 58% (P less than 0.001) and dynamic vascular compliance by approximately 85% (P less than 0.001). The larger dynamic compliance in the inflated lobes appears to have been mainly due to a larger microvascular compliance. The results suggest that atelectasis can result in a stiffer pulmonary capillary bed. This effect appears to be due primarily to the reconfiguration of the lung tissue structure, because replacing the air with an incompressible fluid did not have the same effect. PMID- 1885435 TI - Air interface and elastic recoil affect vascular resistance in three zones of rabbit lungs. AB - We examined the effect of the air interface on pulmonary vascular resistance (PVR) in zones 1, 2, and 3 by comparing pressure-flow data of air- and liquid filled isolated rabbit lungs. Lungs were perfused with Tyrode's solution osmotically balanced with 1% albumin and 4% dextran and containing the vasodilator papaverine (0.05 mg/ml). Lung volume was varied by negative pleural pressure form 0 to -25 cmH2O. Pulmonary artery (Ppa) and venous (Ppv) pressures were fixed at various levels relative to the lung base. Alveolar pressure (PA) was always zero, and perfusate flow was measured continuously. In zone 1 Ppa was 2.5 cmH2O and Ppv was -15 cmH2O. In zone 2 Ppa was 10 cmH2O and Ppv was -5 cmH2O. In zone 3 Ppa was 15 cmH2O and Ppv was 8 cmH2O. We found that in zone 1 the interface was essential for perfusion, but in zones 2 and 3 it had much lesser effects. In general, PVR depended almost uniquely (i.e., with small hysteresis) on transpulmonary pressure, whereas a large hysteresis existed between PVR and lung volume. PVR was high in collapsed and especially in atelectatic lungs, fell sharply with moderate inflation, and within the ranges of vascular pressure studied did not rise again toward total lung capacity. These results suggest that in zone 1 the interface maintains the patency of some alveolar vessels, probably in corners. The majority of alveolar septal vessels appears to be exposed directly to PA in zones 2 and 3, because at equal transpulmonary pressure the PVR is similar in the presence or absence of an interface. PMID- 1885436 TI - Confidence intervals of respiratory mechanical properties derived from transfer impedance. AB - Short-term intraindividual variability of the parameters derived from respiratory transfer impedance (Ztr) measured from 4 to 32 Hz was studied in 10 healthy subjects. The corresponding 95% confidence intervals (CIo) were compared with those computed from a single set of data (CIL) according to Lutchen and Jackson (J. Appl. Physiol. 62: 403-413, 1987). Ztr was analyzed with the six-coefficient model of DuBois et al. (J. Appl. Physiol. 8: 587-594, 1956), which includes airway resistance (Raw) and inertance (Iaw), tissue resistance (Rti), inertance (Iti), and compliance (Cti), and alveolar gas compressibility (Cg). The lowest variability was seen for Iaw (CIo = 11.1%), closely followed by Raw (14.3%) and Cti (14.8%), and the largest for Rti and Iti (24.6 and 93.6%, respectively). Using a simpler model, where Iti was excluded, significantly decreased the variability of Iaw (P less than 0.01) and Rti (P less than 0.05) but was responsible for a systematic decrease of Raw and Iaw and increase of Rti. Except for Raw with both models and Iaw with the simpler model, CIL was greater than CIo. Whatever the model, a high correlation between both sets of confidence intervals was found for Rti and Iaw, whereas no correlation was seen for Raw. This suggests that the variability of the former coefficients mainly reflects experimental noise, whereas that of the latter is largely due to biological variability. PMID- 1885437 TI - Restriction of regional blood flow and diaphragmatic contractility. AB - We have tested the hypothesis that the diaphragmatic head-to-head arterial anastomosis system should maintain adequate diaphragmatic function even during occlusion of some of its arteries. In six anesthetized open-chest dogs, left phrenic vein blood flow (Qphv) was measured by pulsed Doppler flowmetry. Contractility was measured by sonomicrometry in the left costal and crural diaphragm. The diaphragm was paced for 15 min by continuous bilateral supramaximal phrenic nerve stimulation. In five separate runs the following arteries were occluded at minute 5: 1) left phrenic artery, 2) internal mammary artery (IMA), 3) left phrenic artery and IMA, 4) descending aorta, and 5) descending aorta and IMA. Occlusion was then released at minute 10 of the run. In runs 1-3 there were no changes in contractility in costal or crural diaphragm and no changes in Qphv. However, in runs 4 and 5, Qphv decreased to 55.2 +/- 7.4 and 24.0 +/- 6.5% of control values, respectively. In run 4, percent maximum shortening from functional residual capacity (%LFRC) of the crural diaphragm decreased by 39.1%, while %LFRC of the costal diaphragm increased by 41.4% and abdominal pressure decreased by 47.0%. In run 5, abdominal pressure decreased by 53.5% and %LFRC of the crural and costal diaphragm decreased by 45.5 and 5.8%, respectively. Also relative postocclusion hyperemia was greater in run 5 (64.8%) than in run 4 (40.2%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1885438 TI - Effects of prolonged inhalation of N-formyl-methionyl-leucyl-phenylalanine in rabbits. AB - On the basis of its potent proinflammatory and spasmogenic effects, N-formyl methionyl-leucyl-phenylalanine (FMLP), a bacterial oligopeptide, is a putative mediator of bronchoconstriction and airway inflammation during bacterial bronchial infection. However, after an FMLP dose-response curve in rabbits, tachyphylaxis to a second challenge was seen in some rabbits and airway inflammation was absent. This study was designed to reproduce the more prolonged airway exposure to FMLP that may occur during bacterial infection. Two groups of rabbits received FMLP [5 mg/ml in 66% dimethyl sulfoxide- (DMSO) saline] or DMSO diluent alone by nebulization every 15 min for 2 h. Pulmonary resistance (RL) was measured at 1 and 2 h. Recovery from bronchoconstriction was also assessed by measuring RL every 30 min for 2 h after the final FMLP administration. Sections of trachea and large bronchi were prepared and graded by quadrant from 0 to 3 for inflammation, a total score from 0 to 12 being given for each section. There was a progressive increase in RL in FMLP-treated rabbits, reaching 68 +/- 9% above baseline after 120 min, a significantly greater change than after diluent, 8 +/- 12% (P less than 0.01). RL remained elevated above baseline for 90 min after the final FMLP dose. Inflammation scores were greater after FMLP than DMSO: 9.3 +/- 0.5 vs. 4.3 +/- 0.7 (P less than 0.01) in trachea and 5.2 +/- 0.4 vs. 1.7 +/- 0.5 (P less than 0.01) in lobar bronchi. We conclude that prolonged exposure of airways to FMLP produces a sustained increase in RL and airway inflammation, the cardinal features of infective exacerbations of chronic airflow limitation. PMID- 1885439 TI - Changes of zero-stress state of rat pulmonary arteries in hypoxic hypertension. AB - Zero-stress state of the main pulmonary arteries, from the main trunk to a vessel with a lumen diameter approximately 60 microns, was determined in 25 normal control and 38 hypoxic pulmonary hypertensive rats. Pulmonary hypertension was induced by placing the rats in a hypoxic chamber with 10% O2-90% N2 at atmospheric pressure. The zero-stress state of each vessel was obtained by first cutting the vessel transversely into a series of rings and then cutting each ring radially, whereupon the ring opened into a sector, which is characterized by an opening angle defined as the angle subtended between two lines originating from the midpoint of the inner wall (endothelium) to the tips of the inner wall. Whereas the pulmonary blood pressure increased monotonically during the development of pulmonary hypertension, the opening angle followed a different course; e.g., the values (means +/- SD) of the opening angle at the pulmonary trunk at times 0 (control) and 2, 12, 28, 96, 144, 240, 480, and 720 h after exposure to hypoxia are, respectively, 294 +/- 30 degrees, 378 +/- 24 degrees, 385 +/- 12 degrees, 374 +/- 11 degrees, 246 +/- 63 degrees, 267 +/- 49 degrees, 193 +/- 19 degrees, 195 +/- 83 degrees, and 239 +/- 38 degrees. Trends at other places on the artery are similar, but the magnitudes differ. In this period of time, intimal edema and thickening were found. The intima media thickened rapidly from 48 to 240 h and then more slowly from 240 to 720 h. Adventitia thickened later; its thickness exceeded that of the intima media at approximately 96 h. Thus the changes of zero-stress state of the pulmonary arteries are seen to be related to the nonuniform remodeling of the vessel wall as revealed by the edema, blebs, and thickening of different layers. PMID- 1885440 TI - Neutrophil-associated lung injury after the infusion of activated plasma. AB - Previous studies from our laboratory have shown that the infusion of zymosan activated plasma (ZAP) caused large numbers of neutrophils (PMN) to accumulate in the lung. Although PMN are known to be activated by ZAP, it is unclear whether PMN delayed in the lung by ZAP infusion actually cause lung injury. The present study was designed to examine this question by measuring airway epithelial and endothelial injury. Airway epithelial injury was determined by depositing a known dose of fluorescein isothiocyanate-labeled dextran in the lung and measuring its appearance in the blood, and endothelial injury was measured by injecting colloidal carbon and measuring its accumulation in the microvasculature of the lung. The data show that ZAP infusion caused a mild epithelial and endothelial injury that did not increase either extravascular water or protein. This injury could be prevented either by depleting the animals of PMN or by pretreating them with indomethacin. In addition, the effect of ZAP infusion could be partially restored by transfusing donor PMN into the PMN-depleted animals. We conclude that ZAP infusion produces a mild lung injury that is dependent on PMN and the products of the cyclooxygenase pathway of arachidonic acid metabolism. PMID- 1885441 TI - Behavioral arousal in newborn infants and its association with termination of apnea. AB - Arousal is an important protective mechanism that aids in the resolution of obstructive sleep apnea in adults and children, but its role in neonatal apnea has not been investigated. The primary aim of the present study was to determine the role of arousal in the termination of apnea in preterm infants. Videorecording was used to identify spontaneous behavioral arousal in a group of healthy full-term (n = 7) and preterm (n = 10) infants before and during polygraphic monitoring of cardiorespiratory variables and in a group of preterm infants with apnea (n = 10) during similar polygraphic monitoring. Spontaneous arousal rates (mean +/- SE) in full-term infants before and during polygraphic monitoring were 0.18 +/- 0.03 and 0.23 +/- 0.07 episodes/min, respectively. Corresponding values in nonapneic preterm infants were 0.24 +/- 0.03 and 0.24 +/- 0.02 episodes/min. In apneic preterm infants, mean spontaneous arousal rate during polygraphic recording was 0.26 +/- 0.02, but it was considerably higher during apneic sleep periods (0.59 +/- 0.17) than during nonapneic sleep periods (0.25 +/- 0.01). The frequency of occurrence of arousal was significantly higher (P less than 0.005) in long vs. short apnea, mixed vs. central apnea, and severe vs. mild apnea. Although a clear association between arousal and apneic resolution was observed in preterm infants, lack of arousal responses in a large number of apneic episodes suggests that behavioral arousal is not essential for the termination of apnea in these infants. PMID- 1885442 TI - Muscle acetylcholinesterase adapts to compensatory overload by a general increase in its molecular forms. AB - We have investigated the impact of compensatory overload on the content of acetylcholinesterase (AChe) molecular forms in the rat fast-twitch medial gastrocnemius (MG). Overload was induced by way of a bilateral tenotomy of the MG's functional synergists coupled to a daily walking training program (15 m/min, 30% incline, up to 60 min per session, 12-18 wks). This latter condition ensured that the MG were used on a regular basis. In comparison to control values, overloaded MG showed 25 and 19% increases (P less than 0.05) in muscle wet weight and protein concentration, respectively. The content in AChe (activity per muscle) was also increased in these MG (28%, P less than 0.05). Sedimentation analyses revealed a general elevation in the content of AChe molecular forms, with A8, G2, and G1 displaying significant changes (35-42%, P less than 0.05). In a second group of rats, daily running training (27 m/min, 30% incline, using the same timetable) was supplemented to the compensatory overload. In this group, the additional running training led to a greater hypertrophic response as attested to by increases (P less than 0.05) in the MG wet weight (41%) and protein concentration (35%) in comparison to controls. However, total AChe content of these muscles was increased to an extent similar to that observed in the MG subjected only to compensatory overload (24%, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1885443 TI - Muscle damage induced by eccentric contractions of 25% strain. AB - Contractile and morphological properties were measured in the rabbit tibialis anterior muscle 1 h after isometric contraction (IC), passive stretch (PS), or eccentric contraction (EC). Maximal tetanic tension (Po) was reduced after 30 min of PS (P less than 0.001), IC (P less than 0.001), or EC (P less than 0.0001). However, the magnitude of the force deficit was a function of the treatment method. After 30 min of cyclic PS, Po decreased by 13%, whereas after IC or EC, Po decreased by 31 and 69%, respectively. The time course of tension decline in the various groups suggested that the EC-induced injury occurred during the first few minutes of treatment. Although the morphology of samples from the PS and IC groups appeared normal, eccentrically exercised muscles exhibited portions of abnormally large fibers (diam greater than or equal to 110 microns) when viewed in cross section. Examination of 231 such fibers from 6 muscles revealed that all enlarged fibers were exclusively of the fast-twitch glycolytic fiber type. Although no ultrastructural abnormalities were observed in any of the muscles from the IC or PS groups, a significant portion of the fibers in the EC group displayed various degrees of disorganization of the sarcomeric band pattern. Taken together, these studies highlight the importance of fiber oxidative capacity in EC-induced injury, which may be related to the damage mechanism. PMID- 1885444 TI - Respiratory-related recruitment of the masseter: response to hypercapnia and loading. AB - To test the hypothesis that a muscle that closes the jaw, the masseter, can be recruited by ventilatory stimuli, we studied the electromyographic activation of the masseter and genioglossus in seven normal awake males who were exposed in random order to progressive hyperoxic hypercapnia, inspiratory threshold loading (-40 cmH2O), and combined hypercapnia and loading. With hypercapnia, the masseter was generally recruited after the genioglossus had been activated. Once recruited, activation of both muscles increased linearly with increasing CO2. Combined hypercapnia and loading produced more activation than either stimulus alone. These data indicate that the masseter is activated by ventilatory stimuli that activate the genioglossus. Earlier recruitment of the genioglossus suggests that activation of the masseter serves to stabilize the mandible and allow the genioglossus to function as a more efficient dilator of the upper airway. PMID- 1885446 TI - Evidence that the effect of physical exercise on NK cell activity is mediated by epinephrine. AB - The present study was designed to test the hypothesis that the changes in natural killer (NK) cell activity in response to physical exercise were mediated by increased epinephrine concentrations. Eight healthy volunteers 1) exercised on a bicycle ergometer (60 min, 75% of maximal O2 uptake) and 2) on a later day were given epinephrine as an intravenous infusion to obtain plasma epinephrine concentrations comparable with those seen during exercise. Blood samples were collected in the basal state, during the last minutes of exercise or epinephrine infusion, and 2 h later. The NK cell activity (lysis/fixed number of mononuclear cells) increased during exercise and epinephrine infusion and dropped below basal levels 2 h afterward. The increased NK cell activity during exercise and the epinephrine infusion resulted from an increased concentration of NK (CD16+) cells in the peripheral blood. On the other hand, the decreased NK cell activity demonstrated 2 h after exercise and epinephrine infusion did not simply reflect preferential removal of NK cells from the blood, because the proportion of CD16+ cells was normalized. On the basis of the finding that indomethacin abolished the suppressed NK cell activity in vitro and the demonstration of a twofold increase in the proportion of monocytes (CD14+ cells) 2 h after exercise and epinephrine infusion, we suggest that, after stress, prostaglandins released by monocytes are responsible for downregulation of NK cell function. Our findings support the hypothesis that increased plasma epinephrine during physical stress causes a redistribution of mononuclear subpopulations that results in altered function of NK cells. PMID- 1885445 TI - EMG patterns of rat ankle extensors and flexors during treadmill locomotion and swimming. AB - Intramuscular electromyography (EMG) was used to determine and compare the recruitment patterns of the rat soleus (Sol), tibialis anterior (TA), and a deep and a superficial portion of the medial gastrocnemius (MG) during treadmill locomotion at various speeds and inclines and during swimming. Raw EMG signals for 10-20 step or stroke cycles were rectified, averaged, and processed to determine cycle period (EMG onset of one cycle to EMG onset of the next cycle), EMG burst duration, and integrated area of the rectified burst (IEMG). Mean EMG per burst was calculated as IEMG/burst duration. IEMG/min was calculated as IEMG times the number of bursts (cycles) per minute. Cycle period and burst duration of the extensors decreased hyperbolically, while the TA burst duration was unchanged, with increased treadmill speed. With increased treadmill speed, IEMG was decreased in the Sol and unchanged in the MG and TA, whereas IEMG/min decreased in the Sol and increased in the MG and TA. An elevation in treadmill incline resulted in an increase in the activation levels of the MG but not in the Sol or TA. These data indicate that the additional power required at increased speeds and/or inclines of treadmill locomotion is derived from the recruitment of the fast extensors, e.g., the MG. The mean cycle period during swimming was similar to that observed during the fastest treadmill locomotion. EMG burst durations and amplitudes, however, were higher in the TA, relatively similar in the MG, and lower in the Sol during swimming than treadmill locomotion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1885447 TI - Mitogenic response of T-lymphocytes to exercise training and stress. AB - The impact of exercise training and stress on the immune response was examined by measuring the mitogenic response of spleen lymphocytes to the T-cell mitogen concanavalin A (Con-A). Male Sprague-Dawley rats were divided into four groups: sedentary controls (n = 11), handled controls (n = 12), treadmill runners (n = 10), and voluntary runners (n = 11) housed in running wheels. The treadmill group ran at 22 m/min (0.8 mph) for 45 min, 5 days/wk for 8 wk. After the training period, spleen lymphocytes isolated from each rat were incubated with Con-A for 54 h, pulsed with radiolabeled thymidine for 18 h, and counted for tritium activity. Counts per minute per group (means +/- SE) were as follows: sedentary, 6,839 +/- 1,461; handled, 8,959 +/- 1,576; voluntary runners, 13,126 +/- 2,069; and treadmill runners, 18,950 +/- 5,975. One-way analysis of variance and Tukey's highly significant difference test found the counts per minute of the treadmill runners to be significantly different from the counts per minute of the sedentary animals. These results indicate that the responsiveness of spleen lymphocytes to Con-A increases as the level of stress and exercise increases. PMID- 1885448 TI - Respiratory responses to aortic and carotid chemoreceptor activation in the dog. AB - Respiratory responses arising from both chemical stimulation of vascularly isolated aortic body (AB) and carotid body (CB) chemoreceptors and electrical stimulation of aortic nerve (AN) and carotid sinus nerve (CSN) afferents were compared in the anesthetized dog. Respiratory reflexes were measured as changes in inspiratory duration (TI), expiratory duration (TE), and peak averaged phrenic nerve activity (PPNG). Tonic AN and AB stimulations shortened TI and TE with no change in PPNG, while tonic CSN and CB stimulations shortened TE, increased PPNG, and transiently lengthened TI. Phasic AB and AN stimulations throughout inspiration shortened TI with no changes in PPNG or the following TE; however, similar phasic stimulations of the CB and CSN increased both TI and PPNG and decreased the following TE. Phasic AN stimulation during expiration decreased TE and the following TI with no change in PPNG. Similar stimulations of the CB and CSN decreased TE; however, the following TI and PPNG were increased. These findings differ from those found in the cat and suggest that aortic chemoreceptors affect mainly phase timing, while carotid chemoreceptors affect both timing and respiratory drive. PMID- 1885449 TI - Pressure dependence of baroreceptor-mediated vasoconstriction in rat skeletal muscle. AB - To determine whether microvessels in resting or contracting skeletal muscle constrict during baroreceptor activation, vascular diameters were measured in the spinotrapezius muscle of adult rats (n = 12) during occlusion of the common carotid arteries. Neural and myogenic components were distinguished using two types of occlusion: 1) "normal" (arterial pressure was allowed to increase with baroreceptor activation) and 2) "isobaric" (arterial pressure was maintained constant by decreasing blood volume). During normal occlusions, intermediate and small arteriolar diameters decreased in resting and contracting muscle (10-15% and 25-30%, respectively). Large arterioles and all-sized venules distended slightly (approximately 5%) in resting muscle, but diameters were maintained or decreased in contracting muscle. When arterial pressure was maintained constant (isobaric), the microvascular responses to baroreceptor activation in both resting and contracting muscle were essentially eliminated. We conclude that nearly all the arteriolar constriction observed in the spinotrapezius muscle during normal carotid artery occlusion is myogenic in origin, secondary to increased arterial pressure. This pressure-dependent constriction is augmented during skeletal muscle contraction and functional vasodilation. PMID- 1885450 TI - Blood flow distribution within the rib cage muscles. AB - We used 15-microns radiolabeled microspheres to study the regional distribution of blood flow (Q) among parasternal (PS), transversus thoracis, and external (EI) and internal intercostal muscles (II) in nine anesthetized supine mongrel dogs. We measured Q (ml.min-1.100 g-1) in each intercostal space (ICS) during spontaneous breathing, inspiratory resistive loading, and mechanical ventilation following paralysis. At necropsy the EI, II, and PS were excised and sampled separately for each ICS. During paralysis there was no consistent gradient in Q among the PS, II, and EI muscles. During spontaneous breathing, Q to PS increased linearly by 125% between the first and fourth to sixth ICS, Q to EI decreased progressively from the first/second ICS to the fifth/sixth ICS, whereas Q to the II was uniform. During inspiratory resistive loading, in which mouth pressures of -16 +/- 4 cmH2O were generated, the PS gradient was similar to that during spontaneous breathing. Also, Q to the EI increased in the cranial interspaces (P less than 0.02), whereas Q to the II of the seventh/eighth ICS was greater than that of the first/second ICS (P less than 0.001). Furthermore, with loading, ventrodorsal gradients in Q appeared within both EI and II interspaces. There was no consistent gradient in Q within the transversus thoracis muscle during any of the interventions. Our results demonstrate nonuniform Q within PS, EI, and II during both spontaneous and inspiratory resistive loaded breathing. On the assumption that changes in Q reflect changes in activation, our results suggest systematic topographical patterns of recruitment of rib cage respiratory muscles. PMID- 1885452 TI - Influence of sleep on tensor palatini EMG and upper airway resistance in normal men. AB - We propose that a sleep-induced decrement in the activity of the tensor palatini (TP) muscle could induce airway narrowing in the area posterior to the soft palate and therefore lead to an increase in upper airway resistance in normal subjects. We investigated the TP to determine the influence of sleep on TP muscle activity and the relationship between changing TP activity and upper airway resistance over the entire night and during short sleep-awake transitions. Seven normal male subjects were studied on a single night with wire electrodes placed in both TP muscles. Sleep stage, inspiratory airflow, transpalatal pressure, and TP moving time average electromyogram (EMG) were continuously recorded. In addition, in two of the seven subjects the activity (EMG) of both the TP and the genioglossus muscle simultaneously was recorded throughout the night. Upper airway resistance increased progressively from wakefulness through the various non-rapid-eye-movement sleep stages, as has been previously described. The TP EMG did not commonly demonstrate phasic activity during wakefulness or sleep. However, the tonic EMG decreased progressively and significantly (P less than 0.05) from wakefulness through the non-rapid-eye-movement sleep stages [awake, 4.6 +/- 0.3 (SE) arbitrary units; stage 1, 2.6 +/- 0.3; stage 2, 1.7 +/- 0.5; stage 3/4, 1.5 +/- 0.8]. The mean correlation coefficient between TP EMG and upper airway resistance across all sleep states was (-0.46). This mean correlation improved over discrete sleep-awake transitions (-0.76). No sleep induced decrement in the genioglossus activity was observed in the two subjects studied.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1885451 TI - Presynaptic regulation of cardiac sympathetic function in hypoxic guinea pigs. AB - In the normal heart, presynaptic cholinergic muscarinic and alpha 2-adrenergic mechanisms modify the fractional rate constant for norepinephrine (NE) synthesis (kNE), an index of sympathetic neural function. To evaluate presynaptic regulation of kNE, conscious guinea pigs subjected to normoxia and then hypoxia (n = 7-8 in each group) were pretreated with 1) vehicle; 2) a cholinergic muscarinic antagonist, methyl atropine; 3) an alpha 2-antagonist, yohimbine; or 4) a combination of the two. An increase of kNE was determined from incorporation of radiolabeled tyrosine into NE in a control period (arterial PO2 130 +/- 1.7 Torr, PCO2 36 +/- 0.5 Torr) and during a hypoxic state (PO2 49.6 +/- 1.0 Torr, PCO2 36 +/- 0.5 Torr). Hypoxia activated kNE in the atrioventricular node and right ventricular moderator band in vehicle-treated animals (P less than 0.05). Sympathetic activation was more general, however, because alpha 2-presynaptic influence acted to limit kNE in all tissues tested (P less than 0.05) except muscle, spleen, and posterior left ventricle. Cholinergic muscarinic presynaptic restraint on kNE was detected during hypoxia only in the left atrial appendage and lung (P less than 0.05). These data indicate that hypoxia increases kNE in the heart, but restraint by cholinergic muscarinic and alpha 2-adrenergic presynaptic mechanisms limits increases in neurotransmitter synthesis and noradrenergic activation regionally. PMID- 1885453 TI - Maximum expiratory flow-volume curves during short periods of microgravity. AB - To elucidate the effect of normal gravitation on the shape of the maximum expiratory flow-volume (MEFV) curve, we studied nine normal subjects in a National Aeronautics and Space Administration microgravity research aircraft. They performed multiple MEFV maneuvers at 0, 1, and approximately 2 G. The MEFV curves for each subject were filtered, aligned at residual volume, and ensemble averaged to produce an average MEFV curve for each state, allowing differences to be studied. Most subjects showed a decrease in the forced vital capacity at 0 G, which we attribute to an increased intrathoracic blood volume. In most of these subjects, the mean lung volume associated with a given flow was lower at 0 G over about the upper half of the vital capacity. This is similar to the change previously reported during headout immersion and is consistent with the known effect of engorgement of the lung with blood on elastic recoil. There were also consistent but highly individual changes in the position and magnitude of detailed features of the curve, the individual patterns being similar to those previously reported on transition from the erect to the supine position. This supports the idea that the location and motion of choke points that determine the detailed individual configuration of MEFV curves can be significantly influenced by gravitational forces, presumably via the effects of change in longitudinal tension on local airway pressure-diameter behavior and thus wave speed. PMID- 1885454 TI - Cerebral O2 metabolism and cerebral blood flow in humans during deep and rapid eye-movement sleep. AB - It could be expected that the various stages of sleep were reflected in variation of the overall level of cerebral activity and thereby in the magnitude of cerebral metabolic rate of oxygen (CMRO2) and cerebral blood flow (CBF). The elusive nature of sleep imposes major methodological restrictions on examination of this question. We have now measured CBF and CMRO2 in young healthy volunteers using the Kety-Schmidt technique with 133Xe as the inert gas. Measurements were performed during wakefulness, deep sleep (stage 3/4), and rapid-eye-movement (REM) sleep as verified by standard polysomnography. Contrary to the only previous study in humans, which reported an insignificant 3% reduction in CMRO2 during sleep, we found a deep-sleep-associated statistically highly significant 25% decrease in CMRO2, a magnitude of depression according with studies of glucose uptake and reaching levels otherwise associated with light anesthesia. During REM sleep (dream sleep) CMRO2 was practically the same as in the awake state. Changes in CBF paralleled changes in CMRO2 during both deep and REM sleep. PMID- 1885455 TI - Pulmonary and chest wall mechanics in anesthetized paralyzed humans. AB - Pulmonary and chest wall mechanics were studied in 18 anesthetized paralyzed supine humans by use of the technique of rapid airway occlusion during constant flow inflation. Analysis of the changes in transpulmonary pressure after flow interruption allowed partitioning of the overall resistance of the lung (RL) into two compartments, one (Rint,L) reflecting airway resistance and the other (delta RL) representing the viscoelastic properties of the pulmonary tissues. Similar analysis of the changes in esophageal pressure indicates that chest wall resistance (RW) was due entirely to the viscoelastic properties of the chest wall tissues (delta RW = RW). In line with previous measurements of airway resistance, Rint,L increased with increasing flow and decreased with increasing volume. The opposite was true for both delta RL and delta RW. This behavior was interpreted in terms of a viscoelastic model that allowed computation of the viscoelastic constants of the lung and chest wall. This model also accounts for frequency, volume, and flow dependence of elastance of the lung and chest wall. Static and dynamic elastances, as well as delta R, were higher for the lung than for the chest wall. PMID- 1885456 TI - Abdominal distension alters regional pleural pressures and chest wall mechanics in pigs in vivo. AB - Abdominal distension (AD) occurs in pregnancy and is also commonly seen in patients with ascites from various causes. Because the abdomen forms part of the "chest wall," the purpose of this study was to clarify the effects of AD on ventilatory mechanics. Airway pressure, four (vertical) regional pleural pressures, and abdominal pressure were measured in five anesthetized, paralyzed, and ventilated upright pigs. The effects of AD on the lung and chest wall were studied by inflating a liquid-filled balloon placed in the abdominal cavity. Respiratory system, chest wall, and lung pressure-volume (PV) relationships were measured on deflation from total lung capacity to residual volume, as well as in the tidal breathing range, before and 15 min after abdominal pressure was raised. Increasing abdominal pressure from 3 to 15 cmH2O decreased total lung capacity and functional residual capacity by approximately 40% and shifted the respiratory system and chest wall PV curves downward and to the right. Much smaller downward shifts in lung deflation curves were seen, with no change in the transdiaphragmatic PV relationship. All regional pleural pressures increased (became less negative) and, in the dependent region, approached 0 cmH2O at functional residual capacity. Tidal compliances of the respiratory system, chest wall, and lung were decreased 43, 42, and 48%, respectively. AD markedly alters respiratory system mechanics primarily by "stiffening" the diaphragm/abdomen part of the chest wall and secondarily by restricting lung expansion, thus shifting the lung PV curve as seen after chest strapping. The less negative pleural pressures in the dependent lung regions suggest that nonuniformities of ventilation could also be accentuated and gas exchange impaired by AD. PMID- 1885457 TI - Cardiovascular responses of heart transplant patients to exercise training. AB - Orthotopic heart transplantation (OHT) represents an effective alternative for individuals with end-stage heart disease. The current literature reports only the responses of OHT patients to greater than or equal to 4 mo of exercise training (ET) and frequently lacks adequate controls. Most programs currently treating OHT patients usually provide 6-12 wk of ET. This study describes the effects of a 10 wk supervised ET program in 12 male OHT patients and 5 other male OHT patients who served as a comparison group. Graded exercise tests were performed before and after ET. After ET, maximal O2 consumption was significantly greater for the ET group than the comparison group (P less than 0.05) and the mean increase in peak heart rate was 18 +/- 4 and 6 +/- 4 (SE) min-1 for ET and comparison groups, respectively (P less than 0.05). Maximal ventilation was also significantly greater for the ET group at after ET, while resting heart rate and blood pressure and peak blood pressure, O2 pulse, respiratory rate, and ventilatory equivalents for O2 and CO2 were not significantly changed. We conclude that after OHT a 10-wk ET program improves maximal O2 consumption and, by improving peak heart rate, improves O2 delivery. PMID- 1885458 TI - Expiratory muscle fatigue in normal subjects. AB - We examined expiratory muscle fatigue during expiratory resistive loading in 11 normal subjects. Subjects breathed against expiratory resistances at their own breathing frequency and tidal volume until exhaustion or for 60 min. Respiratory muscle strength was assessed from both the maximum static expiratory and inspiratory mouth pressures (PEmax and PImax). At the lowest resistance, PEmax and PImax measured after completion of the expiratory loaded breathing were not different from control values. With higher resistance, both PEmax and PImax were decreased (P less than 0.05), and the decrease lasted for greater than or equal to 60 min. The electromyogram high-to-low frequency power ratio for the rectus abdominis muscle decreased progressively during loading (P less than 0.01), but the integrated EMG activity did not change during recovery. Transdiaphragmatic pressure during loading was increased 3.6-fold compared with control (P less than 0.05). These findings suggest that expiratory resistive loaded breathing induces muscle fatigue in both expiratory and inspiratory muscles. Fatigue of the expiratory muscles can be attributed directly to the high work load and that of the inspiratory muscles may be related to increased work due to shortened inspiratory time. PMID- 1885459 TI - Endotoxemia and release of tumor necrosis factor and interleukin 1 alpha in acute heatstroke. AB - To determine whether endotoxemia and release of tumor necrosis factor (TNF-alpha) and/or interleukin 1 alpha (IL-1 alpha) are involved in the pathogenesis of heatstroke, 17 adult patients with a mean rectal temperature of 42.1 +/- 0.2 degrees C were studied. Blood samples were taken on admission and after cooling was completed. TNF-alpha and IL-1 alpha levels were measured by enzyme-linked immunosorbent assay, and lipopolysaccharide (LPS) content was measured by the chromogenic substrate modification of the Limulus amebocyte lysate. TNF-alpha, IL 1 alpha, and LPS were elevated in all patients [199 +/- 25 (SE) pg/ml, 480.5 +/- 68.3 pg/ml, and 8.60 +/- 1.19 ng/ml, respectively, compared with normal control values of 31.4 +/- 8.4 pg/ml, 53.7 +/- 5.32 pg/ml, and less than 9 pg/ml]. There was no significant correlation between temperature and the circulating concentration of TNF-alpha, IL-1 alpha, and LPS. Postcooling TNF-alpha, IL-1 alpha, and LPS concentrations were significantly decreased but still above normal control values. The findings suggest that these mediators may have a role in the pathogenesis of heatstroke that could change the strategy of management. PMID- 1885460 TI - Role for tumor necrosis factor as mediator of lung injury following lower torso ischemia. AB - Ischemia and reperfusion of the ischemic lower torso lead to a neutrophil- (PMN) dependent lung injury characterized by PMN sequestration and permeability edema. This mimics the injury seen after infusion of tumor necrosis factor alpha (TNF), a potent activator of PMN and endothelium. This study tests whether TNF is a mediator of the lung injury after lower torso ischemia. Anesthetized rats underwent 4 h of bilateral hindlimb tourniquet ischemia, followed by reperfusion for 10 min, 30 min, 1, 2, 3, and 4 h (n = 6 for each time point). Quantitative lung histology indicated progressive sequestration of PMN in the lungs, 25 +/- 3 (SE) PMN/10 high-power fields (HPF) 10 min after reperfusion vs. 20 +/- 2 PMN/10 HPF in sham animals (NS), increasing to 53 +/- 5 PMN/10 HPF after 4 h vs. 23 +/- 3 PMN/10 HPF in sham animals (P less than 0.01). There was lung permeability, shown by increasing protein accumulation in bronchoalveolar lavage (BAL) fluid, which 4 h after reperfusion was 599 +/- 91 vs. 214 +/- 35 micrograms/ml in sham animals (P less than 0.01). Similarly, there was edema, shown by the lung wet-to dry weight ratio, which increased by 4 h to 4.70 +/- 0.12 vs. 4.02 +/- 0.17 in sham animals (P less than 0.01). There was generation of leukotriene B4 in BAL fluid (720 +/- 140 vs. 240 +/- 40 pg/ml, P less than 0.01), and in three of six rats tested at this time TNF was detected in plasma, with a mean value of 167 pg/ml. TNF was not detectable in any sham animal.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1885461 TI - Cardiovascular adaptations in Andean natives after 6 wk of exposure to sea level. AB - Six male Quechua Indians (34.0 +/- 1.1 yr, 159.5 +/- 2.1 cm, 60.5 +/- 1.6 kg), life-long residents of La Raya, Peru (4,350-m altitude with an average barometric pressure of 460 Torr), were studied using noninvasive methods to determine the structural and functional changes in the cardiovascular system in response to a 6 wk deacclimation period at sea level. Cardiac output, stroke volume, and left ventricular ejection fractions were determined using radionuclide angiographic techniques at rest and during exercise on a cycle ergometer at 40, 60, and 90% of a previously determined maximal O2 consumption. Subjects at rest were subjected to two-dimensional and M-mode echocardiograms and a standard 12-lead electrocardiogram. Hemoglobin and hematocrit were measured on arrival at sea level by use of a Coulter Stacker S+ analyzer. After a 6-wk deacclimation period, all variables were remeasured using the identical methodology. Hemoglobin values decreased significantly over the deacclimation period (15.7 +/- 1.1 to 13.5 +/- 1.2 g/dl; P less than 0.01). The results indicate that the removal of these high altitude-adapted natives from 4,300 m to sea level for 6 wk results in only minor changes to the cardiac structure and function as measured by these noninvasive techniques. PMID- 1885463 TI - Regional variation in canine diaphragm thickness. AB - To quantify the relationship between both regional and overall diaphragm morphometry and body weight in the dog, diaphragm thickness was measured in five regions of the costal diaphragm and three regions of the crural diaphragm in 40 healthy dogs (8-40 kg). Surface area of the diaphragm, diaphragm weight, and body weight were also determined. Diaphragm surface area and weight varied linearly with body weight, but there was no significant correlation between overall diaphragm thickness and body weight. Diaphragm thickness varied significantly between regions, and three regions had systematic left-to-right differences as well. Because diaphragm geometry influences the diaphragm's function as a pressure generator, regional differences in thickness may alter the relationship between the force developed by the activation of a particular region of the diaphragm and its action on the respiratory system. PMID- 1885462 TI - Effect of increased Hb-O2 affinity on VO2max at constant O2 delivery in dog muscle in situ. AB - We investigated the effect of increasing hemoglobin- (Hb) O2 affinity on muscle maximal O2 uptake (VO2max) while muscle blood flow, [Hb], HbO2 saturation, and thus O2 delivery (muscle blood flow X arterial O2 content) to the working muscle were kept unchanged from control. VO2max was measured in isolated in situ canine gastrocnemius working maximally (isometric tetanic contractions). The muscles were pump perfused, in alternating order, with either normal blood [O2 half saturation pressure of hemoglobin (P50) = 32.1 +/- 0.5 (SE) Torr] or blood from dogs that had been fed sodium cyanate (150 mg.kg-1.day-1) for 3-4 wk (P50 = 23.2 +/- 0.9). In both conditions (n = 8) arterial PO2 was set at approximately 200 Torr to fully saturate arterial blood, which thereby produced the same arterial O2 contents, and muscle blood flow was set at 106 ml.100 g-1.min-1, so that O2 delivery in both conditions was the same. VO2max was 11.8 +/- 1.0 ml.min-1.100 g 1 when perfused with the normal blood (control) and was reduced by 17% to 9.8 +/- 0.7 ml.min-1.100 g-1 when perfused with the low-P50 blood (P less than 0.01). Mean muscle effluent venous PO2 was also significantly less (26 +/- 3 vs. 30 +/- 2 Torr; P less than 0.01) in the low-P50 condition, as was an estimate of the capillary driving pressure for O2 diffusion, the mean capillary PO2 (45 +/- 3 vs. 51 +/- 2 Torr). However, the estimated muscle O2 diffusing capacity was not different between conditions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1885464 TI - Finite-element solution of thermal conductivity of muscle during cold water immersion. AB - The in vivo or effective thermal conductivity (keff) of muscle tissue of the human forearm was determined through a finite-element (FE) model solution of the bioheat equation. Data were obtained from steady-state temperatures measured in the forearm after 3 h of immersion in water at temperatures (Tw) of 15 (n = 6), 20 (n = 5), and 30 degrees C (n = 5). Temperatures were measured every 0.5 cm from the longitudinal axis of the forearm to the skin approximately 9 cm distal from the elbow. Heat flux was measured at two sites on the skin adjacent to the temperature probe. The FE model is comprised of concentric annular compartments with boundaries defined by the location of temperature measurements. Through this approach, it was possible to include both the metabolic heat production and the convective heat transfer between blood and tissue at two levels of blood flow, one perfusing the compartment and the other passing through the compartment. Without heat exchange at the passing blood flow level, the arterial blood temperature would be assumed to have a constant value everywhere in the forearm muscles, leading to a solution of the bioheat equation that greatly underpredicts keff. The extent of convective heat exchange at the passing blood flow level is estimated to be approximately 60% of the total heat exchange between blood and tissue. Concurrent with this heat exchange is a decrease in the temperature of the arterial blood as it flows radially from the axis to the skin of the forearm, and this decrease is enhanced with a lowered Tw.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1885465 TI - In vivo thermal conductivity of the human forearm tissues. AB - The effective thermal conductivities of the skin + subcutaneous (keff skin + fat) and muscle (keff muscle) tissues of the human forearm at thermal steady state during immersion in water at temperatures (Tw) ranging from 15 to 36 degrees C were determined. Tissue temperature (Tt) was continuously monitored by a calibrated multicouple probe during a 3-h immersion of the resting forearm. Tt was measured every 5 mm from the longitudinal axis of the forearm (determined from computed-tomography scanning) to the skin surface. Skin temperature (Tsk), heat loss (Hsk), and blood flow (Q) of the forearm, as well as rectal temperature (Tre) and arterial blood temperature at the brachial artery (Tbla), were measured during the experiments. When the keff values were calculated from the finite element (FE) solution of the bioheat equation, keff skin + fat ranged from 0.28 +/- 0.03 to 0.73 +/- 0.14 W.degrees C-1.m-1 and keff muscle varied between 0.56 +/- 0.05 and 1.91 +/- 0.19 W.degrees C-1.m-1 from 15 to 36 degrees C. The values of keff skin + fat and keff muscle, calculated from the FE solution for Tw less than or equal to 30 degrees C, were not different from the average in vitro values obtained from the literature. The keff values of the forearm tissues were linearly related (r = 0.80, P less than 0.001) to Q for Tw greater than or equal to 30 degrees C. It was found that the muscle tissue could account for 92 +/- 1% of the total forearm insulation during immersion in water between 15 and 36 degrees C. PMID- 1885466 TI - Influence of vasoconstriction, temperature, and flow on the kinetics of serotonin uptake in rabbit lungs. AB - In the process of estimating the kinetic parameters of the pulmonary endothelial serotonin (5-HT) uptake, it is critically important to distinguish the effects of hemodynamic changes from endothelial injury. Therefore, the effects of changes in flow rate (1.7-5.0 ml/s), hemodynamics (vasoconstriction by norepinephrine), and temperature (39 vs. 33 degrees C) were investigated in isolated rabbit lungs. Indicator-dilution data were expressed in terms of the Michaelis-Menten equation for the two 5-HT uptake pathways in the preparation. The maximum uptake velocity (Vmax1) and the 5-HT concentration at half-maximum velocity (Km1) of the first pathway as well as the first-order constant (Vmax2/Km2) of the linear part of the second pathway were determined. Neither vasoconstriction nor flow variations had any effect on Km1, whereas increasing the flow rate caused extensive recruitment, with a concomitant increase in Vmax1 and Vmax2/Km2. Furthermore, all the kinetic parameters were significantly decreased at the lower temperature. We conclude that Km1 is independent of organ hemodynamics (vasoconstriction and flow) but susceptible to changes in 5-HT uptake capacity caused by a change in temperature. Vmax1 and Vmax2/Km2 respond to alterations in 5-HT uptake capacity and perfused organ volume. These are prerequisites to apply kinetic modeling as a method for the investigation of pulmonary endothelial function and integrity. PMID- 1885467 TI - Intercostal muscle action inferred from finite-element analysis. AB - The external and internal intercostal muscles are important respiratory muscles in humans, but their mechanical actions have been controversial. We used finite element analysis based on anatomic and mechanical measurements in dogs to assess the action of the intercostal and other rib cage muscles in a model of an isolated canine rib cage. When intercostal muscle forces of either the internal or the external layer were applied in a single interspace, they pulled the adjacent ribs together, consistent with published observations in dogs. However, when the forces were applied in all interspaces, the external layer caused an inspiratory motion and the internal layer caused an expiratory motion, consistent with conventional understanding of intercostal muscle actions. Parasternal intercostal, levator costae, and transversus thoracis (triangularis sterni) muscle actions were also simulated. These muscles caused expected movements of the ribs and sternum. We conclude that the actions of intercostal muscles depend on the spatial extent of their activation. Their actions in a single interspace and in multiple interspaces can be observed and explained with three-dimensional finite-element models. PMID- 1885468 TI - Analysis of behavior of the respiratory system in ARDS patients: effects of flow, volume, and time. AB - The effects of inspiratory flow (V) and inflation volume (delta V) on the mechanical properties of the respiratory system in eight ARDS patients were investigated using the technique of rapid airway occlusion during constant-flow inflation. We measured interrupter resistance (Rint,rs), which in humans represents airway resistance, the additional resistance (delta Rrs) due to viscoelastic pressure dissipations and time constant inequalities, and static (Est,rs) and dynamic (Edyn,rs) elastance. The results were compared with a previous study on 16 normal anesthetized paralyzed humans (D'Angelo et al. J. Appl. Physiol. 67: 2556-2564, 1989). We observed that 1) resistance and elastance were higher in ARDS patients; 2) with increasing V, Rint,rs and Est,rs did not change, delta Rrs decreased progressively, and Edyn,rs increased progressively; 3) with increasing delta V, Rint,rs decreased slightly, delta Rrs increased progressively, and Est,rs and Edyn,rs showed an initial decrease followed by a secondary increase noted only in the ARDS patients. The above findings could be explained in terms of a model incorporating a standard resistance in parallel with a standard elastance and a series spring-and-dashpot body that represents the stress adaptation units within the tissues of the respiratory system. PMID- 1885469 TI - Peptidase modulation of noncholinergic vagal bronchoconstriction and airway microvascular leakage. AB - We investigated whether inhibition of neutral endopeptidase 24.11 (NEP) and/or angiotensin-converting enzyme (ACE) modifies vagally induced nonadrenergic noncholinergic (NANC) airflow obstruction and airway microvascular leakage as measured by extravasation of Evans blue dye (intravenous) in anesthetized guinea pigs. We gave phosphoramidon to inhibit NEP and enalapril maleate or captopril to inhibit ACE. Animals pretreated with inhaled phosphoramidon (7.5 or 75 nmol), enalapril maleate (87 or 870 nmol), or captopril (350 nmol) reached higher peak lung resistance (RL) values (14.3 +/- 2.7, 15.7 +/- 3.8, 16.7 +/- 3.8, 11.4 +/- 1.6, and 24.6 +/- 3.5 cmH2O.ml-1.s, respectively) than saline-treated animals (5.9 +/- 1.1; P less than 0.05) after bilateral vagus nerve stimulation (5 Hz, 10 V, 10 ms, 150 s). Intravenous phosphoramidon (1 mg/kg), but not intravenous captopril (6 mg/kg), potentiated peak RL (22.9 +/- 6.9 and 7.1 +/- 1.5 cmH2O.ml 1.s, respectively). Vagal nerve stimulation (1 and 5 Hz) increased the extravasation of Evans blue dye in tracheobronchial tissues compared with sham stimulated animals, but this was not potentiated by inhaled enzyme inhibitors or intravenous captopril. However, intravenous phosphoramidon significantly augmented the extravasation of Evans blue dye in main bronchi and intrapulmonary airways. We conclude that degradative enzymes regulate both NANC-induced airflow obstruction and airway microvascular leakage. PMID- 1885470 TI - Pattern of simulated snoring is different through mouth and nose. AB - Cineradiography of the pharynx during simulated snoring was done in 6 healthy volunteers, and supraglottic pressure and flow rate were recorded in 12 others. We observed, immediately before snoring, a decrease in the sagittal diameter of the oropharynx followed, during snoring, by high-frequency oscillations of soft palate and pharyngeal walls. The pattern of soft palate oscillations was different while snoring through the nose or mouth. During inspiratory snoring through the nose, the soft palate remained in close contact with the back of the tongue and only the uvula presented high-frequency oscillations. Snoring through the mouth resulted in ample high-frequency oscillations of the whole soft palate. Frequency of airflow and supraglottic pressure oscillations was less (P less than 0.05) during mouth (28.2 +/- 7.5 Hz) than during nasal snoring (77.8 +/- 36.7 Hz). This difference may be related to the smaller oscillating mass (i.e., uvula) during nasal snoring. At variance with our previous data, which showed that snoring during sleep, in both heavy (nonapneic) snorers and obstructive sleep apnea patients, was systematically preceded by flow limitation, this was not true during simulated snoring. PMID- 1885471 TI - Respiratory neuronal activity during apnea and other breathing patterns induced by laryngeal stimulation. AB - Respiration cycles through three distinct phases (inspiration, postinspiration, and expiration) each having corresponding medullary cells that are excited during one phase and inhibited during the other two. Laryngeal stimulation is known to induce apnea in newborn animals, but the cellular mechanisms underlying this effect are not known. Intracellular recording of ventral respiratory group neurons was accomplished in intact anesthetized, paralyzed, and mechanically ventilated piglets. Apnea was induced by insufflation of the larynx with ammonia saturated air, smoke, or water. Laryngeal insufflation induced phrenic nerve apnea, stimulation of postinspiratory neurons, and stable membrane potentials in inspiratory and expiratory cells consistent with postinspiratory inhibition. Usually the membrane potential of each neuronal type cycled through an expiratory level before onset of the first recovery breath. Variants of the apnea response, probably reflecting the aspiration reflex or sniffing, sneezing, coughing, and swallowing, were also observed. These latter patterns showed oscillation between inspiration and postinspiration without an apparent intervening stage II expiratory phase. However, stage II expiratory activity always preceded onset of the first ramp inspiration after such a pattern. These findings suggest that activation of postinspiratory mechanisms causes profound alterations in the respiratory pattern and that stage II expiration importantly modulates recovery of ramp inspiratory activity. The mechanism of this latter effect may be inhibition of early inspiratory neurons with consequent postinhibitory rebound. PMID- 1885472 TI - Perialveolar interstitial resistance and compliance in isolated rat lung. AB - We have developed a method to characterize fluid transport through the perialveolar interstitium using micropuncture techniques. In 10 experiments we established isolated perfused rat lung preparations. The lungs were initially isogravimetric at 10 cmH2O arterial pressure, 2 cmH2O venous pressure, and 5 cmH2O alveolar pressure. Perialveolar interstitial pressure was determined by micropuncture at alveolar junctions by use of the servo-null technique. Simultaneously a second micropipette was placed in an alveolar junction 20-40 microns away, and a bolus of albumin solution (3.5 g/100 ml) was injected. The resulting pressure transient was recorded for injection durations of 1 and 4 s in nonedematous lungs. The measurements were repeated after gross edema formation induced by elevated perfusion pressure. We model the interstitium as a homogeneous linearly poroelastic material and assume the initial pressure distribution due to the injection to be Gaussian. The pressure decay is inversely proportional to time, with time constant T, where T is a measure of the ratio of interstitial tissue stiffness to interstitial resistance to fluid flow. A linear regression was performed on the reciprocal of the pressure for the decaying portion of the transients to determine T. Comparing pressure transients in nonedematous and edematous lungs, we found that T was 4.0 +/- 1.4 and 1.4 +/- 0.6 s, respectively. We have shown that fluid transport through the pulmonary interstitium on a local level is sensitive to changes in interstitial stiffness and resistance. These results are consistent with the decreased stiffness and resistance in the perialveolar interstitium that accompany increased hydration. PMID- 1885473 TI - Water and electrolyte balance in the vascular space during graded exercise in humans. AB - We analyzed the changes in water content and electrolyte concentrations in the vascular space during graded exercise of short duration. Six male volunteers exercised on a cycle ergometer at 20 degrees C (relative humidity = 30%) as exercise intensity was increased stepwise until voluntary exhaustion. Blood samples were collected at exercise intensities of 29, 56, 70, and 95% of maximum aerobic power (VO2max). A curvilinear relationship between exercise intensity and Na+ concentration in plasma ([Na+]p) was observed. [Na+]p significantly increased at 70% VO2max and at 95% VO2max was approximately 8 meq/kgH2O higher than control. The change in lactate concentration in plasma ([Lac-]p) was closely correlated with the change in [Na+]p (delta[Na+]p = 0.687 delta[Lac-]p + 1.79, r = 0.99). The change in [Lac-]p was also inversely correlated with the change in HCO3- concentration in plasma (delta[HCO3-]p = -0.761 delta[Lac-]p + 0.22, r = 1.00). At an exercise intensity of 95% VO2max, 60% of the increase in plasma osmolality (Posmol) was accounted for by an increase in [Na+]p. These results suggest that lactic acid released into the vascular space from active skeletal muscles reacts with [HCO3-]p to produce CO2 gas and Lac-. The data raise the intriguing notion that increase in [Na+]p during exercise may be caused by elevated Lac-. PMID- 1885474 TI - A simple disposable continuous-infusion swivel for unrestrained small animals. AB - An easy-to-prepare inexpensive disposable infusion swivel for small animals is described for acute and chronic experiments. The swivel is constructed from common plastic laboratory syringe components, needles, and a three-way stopcock. PMID- 1885475 TI - Renal lesions in leprosy. PMID- 1885476 TI - Renal involvement in leprosy. AB - Renal involvement was studied in 70 patients with leprosy by urine analysis, detailed biochemical investigations and renal histopathology. Of these 70 patients, 40 had lepromatous and 30 had non-lepromatous leprosy. Creatinine clearance was reduced in 20 patients. Renal biopsies were studied in 50 cases (25 lepromatous, 25 non-lepromatous); of which in 13 cases (10 lepromatous, 3 non lepromatous) abnormal histopathological lesions were found by light microscopy. Amyloidosis was seen in only one lepromatous patient. No acid-fast bacilli and leproma like lesion were demonstrated in any case. PMID- 1885477 TI - Hickman catheter implantation in the treatment of acute leukaemia. AB - Between June 1984 and May 1986, 13 Hickman catheters were introduced in 11 patients for the treatment of acute leukaemia. The catheters remained in situ for a mean period of 77 days (range 1-180). Two of the patients developed haematomas at the entry site and one patient had a blockage of the catheter due to a blood clot which required intervention. Six patients had documented bacteraemia which on blood culture showed enteric organisms and was not catheter related. No catheter had to be removed due to a catheter-related complication. Hickman right atrial catheter provides a safe and reliable venous access with minimum complications and is well tolerated by the patient. PMID- 1885478 TI - Abnormal lipoprotein in uraemic patients treated conservatively and by maintenance haemodialysis. AB - Observations of serum lipids and lipoproteins in 35 uraemic patients treated conservatively (20 cases) and by maintenance haemodialysis (15 cases) are presented. Serum triglycerides levels of both groups (243.7 +/- 119.1 and 160.8 +/- 55.0 mg/dl) were significantly higher (p less than 0.001) and high density lipoprotein cholesterol (HDLC) levels (19.0 +/- 6.1 and 12.17 +/- 5.1 mg/dl) were significantly lower (p less than 0.001) in comparison to those in 20 controls. Agarose gel electrophoresis revealed a second, slow migrating pre-beta band in significantly higher percentage of uraemics (55% and 93.3%) as compared to controls (25%). Until the effects of uraemia and chronic haemodialysis on lipoprotein metabolism are better understood, caution should be exercised in the interpretation of HDLC levels in these patients. PMID- 1885479 TI - Immunoclinical correlation in diabetes mellitus. A preliminary report on the lectin-agglutination test. AB - Twenty cases with insulin dependent diabetes mellitus (IDDM) were studied and compared with a control group with non insulin dependent diabetes mellitus (NIDDM) and another group of nondiabetic healthy persons. Lymphocytes of each group were tested for agglutination with three sets of lectins: concavalin A (ConA), soyabean agglutinin (SBA) and peanut agglutinin (PNA). SBA test, being highly positive in IDDM and persistently negative in NIDDM, is the most significant of the three tests for differentiating between the two types of diabetes mellitus. PMID- 1885480 TI - Predicting the immediate outcome of patients with cerebrovascular accident: a prognostic score. AB - A prognostic score was derived from a prospective study of 120 consecutive patients with cerebrovascular accident. Multivariate analysis was used to compare the presenting clinical features of 106 (88%) of these patients with their immediate outcome (survival or death). Similar analysis was also used to compare features on CT scan with immediate outcome in 45 patients. The immediate prognostic features included old age, history of previous stroke, mental obtundation at the onset, persistent altered consciousness greater than or equal to first 48 hours, altered consciousness appearing in the first 24-72 hours, complete hemiplegia, seizures, aspiration pneumonitis, and multiple/massive lesions and gross mass effect on CT scan. The prognostic score derived from discriminant function using CT scan variables was less accurate than that formulated from only clinical variables. In the latter (using clinical variables) a prognostic score of 46 or less suggested a 50% chance of recovery, scores of 47 or more a 50% chance of death, while scores of 12 or less and 63 or more suggested a 99% likelihood of survival and death respectively. PMID- 1885481 TI - Clinical spectrum of myasthenia gravis and problems of management. AB - Seventeen cases of myasthenia gravis, aged 20-79 years, including one case of ocular myasthenia gravis, seen over a 3 year period, were analysed. Dysphagia was the presenting symptom in two cases. One patient had ectopic thymus gland in relation to the cardiac border, which posed difficulty in diagnosis. A majority of the patients were on medical treatment, including neostigmine, prednisolone and azathioprim. Plasmapheresis was done in 4 cases during crisis, with significant benefit. One patient was put on intermittent ventilatory support for 14-16 hours a day for over 2 years; she died during a power failure. Seven patients were subjected to thymectomy. PMID- 1885482 TI - Early onset duodenal ulcer with special reference to serum alpha-1-antitrypsin activity. AB - Thirteen patients of duodenal ulcer, below 20 years of age, ten age and sex matched controls and 17 first probands were studied to find out (i) the special characteristics of this duodenal ulcer subtype and (ii) the serum alpha-1 antitrypsin (alpha-1-AT) activity in these patients and their first probands. Basal and maximal acid output, and serum level of alpha-1-AT were measured, and serum agar gel electrophoresis done, in the above subjects. Special characteristics like positive family history, and high basal (p less than or equal to 0.01) and maximal (p less than or equal to 0.001) acid output were noted in these patients. Serum alpha-1-AT was found to be deficient in nine patients. Five first probands also had the heterozygous level of the enzyme deficiency. Thus, patients of early onset duodenal ulcer seem to have special characteristics with alpha-1-antitrypsin deficiency in them as well as in their first probands. PMID- 1885483 TI - Study of serum myoglobin and serum electrolytes in acute uncomplicated myocardial infarction. AB - Forty patients with uncomplicated acute myocardial infarction were studied within 6-18 hours after the infarction. Serum myoglobin was elevated in all the cases and was markedly high in cases studied 18 hours after the acute infarction, though the level did not show any relation with the severity of the attack. Myoglobin level showed no correlation with SGOT level, which did not rise appreciably within 6 hours. Serum sodium and potassium levels did not show any change, even in the most severe cases. Serum myoglobin estimation is thus a good diagnostic test in the early hours of acute myocardial infarction. PMID- 1885484 TI - Interpretation of treadmill stress test in patients with coronary artery disease receiving beta blocker therapy. AB - Graded maximal treadmill exercise responses were studied before and after beta blockade (atenolol 100 mg once daily for 2 weeks) in 20 male patients with chronic stable angina. Beta-blocking effect consisted of significant reduction of resting heart rate (HR) by 21%, systolic blood pressure (SBP) by 12% and rate pressure product (RPP) by 30%. While the maximum exercise capacity was marginally increased by mean 1.7 min +/- 1.6 SD (P less than 0.001) under the influence of therapy, peak HR, SBP and maximum RPP were significantly lower (P less than 0.001) than in preatenolol exercise tests. Similarly, while the configuration and magnitude of ST segment depression did not differ materially between the pre and post atenolol tests, onset time of ST change was delayed and offset time shortened significantly. These parameters cannot be relied upon to assess the extent and severity of coronary artery disease (CAD) if stress test is carried out while the patient is on a beta-blocking drug. The overall sensitivity of the stress test to detect coronary disease is, however, not likely to be compromised because of negligible influence of beta-blockers upon ST segment depression provided maximally tolerated (not submaximal) exercise is performed. ST/HR slope, an exercise test variable known to correlate well with the extent of CAD, was shown to be uninfluenced by beta-blockade. Its measurement is therefore recommended in interpreting stress tests performed in patients receiving beta blocker therapy. This, however, requires a meticulously prepared protocol of recording computer averaged QRST complexes and multilead ECG tracings at very frequent intervals throughout the exercise.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1885486 TI - Statistics for clinicians. 3. Nominal data (II) AB - When the percentage occurrence of an event in a series of groups shows a linear trend, the standard chi-square test may not reveal its significance. The data should then be analyzed by z-test for a linear trend. When the results of several similar experiments show a trend in favor of one group, but the differences in individual studies are not significant, the data from all studies can be analyzed together by the z-test for significance of the trend. In some studies, patients need to be followed up for long periods for the occurrence of an event. Here, we are interested not only in the frequency of the event, but also how soon it occurs or how long it is delayed. For this purpose the data should be analyzed by the life table method (also known as the logrank method or the Mantel-Haenszel method). Diagnostic tests are usually evaluated by their sensitivity and specificity. However, what is also important for a clinician is their predictive value, which depends on the prevalence of the condition. PMID- 1885485 TI - Continuous infusion of high doses of atropine in the management of organophosphorus compound poisoning. AB - Forty five cases of organophosphorus poisoning were studied to evaluate the results of continuous infusion of high doses of atropine as against the conventional intermittent therapy. A statistically significant reduction in mortality (23.5% to 8.8%; p less than 0.05) was evident in this study as compared to previous years. Pseudocholinesterase levels below 10% of normal were associated with a poor prognosis and increased mortality. PMID- 1885487 TI - Tumour necrosis factor/cachectin: biology and relevance to disease. AB - Tumour necrosis factor/cachectin (TNF) is considered a primary mediator in the pathogenesis of injury, infection and inflammation and seems to be essential for host defense and tissue homeostasis. On the other hand, TNF can also cause septic shock, tissue injury and cachexia. There is a close interaction between TNF and other cytokines such as interferon, interleukin-1 and interleukin-2, and prostaglandins. TNF is responsible for the deleterious effects of endotoxaemia, and passive immunization against it substantially mitigates the lethal effect of endotoxin. It is also a potent pyrogen, causes bone resorption, activates neutrophil adherence and degranulation and phagocytosis, and ultimately participates in inflammatory diseases of the skin, gastrointestinal tract, joints, muscle and central nervous system and in neoplastic diseases. PMID- 1885488 TI - Acute aortic regurgitation. PMID- 1885489 TI - A family with partial androgen insensitivity. PMID- 1885490 TI - Spontaneous rupture of the oesophagus (Boerhaave's syndrome) presenting as pyopneumothorax. AB - Spontaneous rupture of the oesophagus presenting as a pyopneumothorax in an elderly male is described. Delayed presentation of the patient led to serious complications to which he succumbed. PMID- 1885491 TI - Role of aminophylline in atropine resistant atrioventricular block. AB - Atrioventricular (AV) block may be induced by ischaemia as a result of production of adenosine, a metabolite that accumulates during hypoxia and ischaemia. Adenosine antagonism has been shown to reverse experimental AV node block in dogs. Recently, theophylline has been shown to be highly effective in diminishing the frequency and severity of bradycardia in newborn infants with apnoea bradycardia spells. We report here a case of acute inferior wall myocardial infarction who developed atropine resistant AV block which was reversed by aminophylline, a competitive, antagonist of adenosine. PMID- 1885492 TI - Ataxia telangiectasia. PMID- 1885493 TI - Myositis ossificans progressiva. AB - Myositis ossificans progressiva is a rare, incurable disease causing progressive ossification of skeletal muscles leading to total immobility. We report one such case. PMID- 1885494 TI - Cranial chordoma. PMID- 1885495 TI - ERCP in the evaluation of choledochal cyst due to anomalous pancreatobiliary junction. AB - With the application of endoscopic retrograde cholangio pancreatography (ERCP), the association of anomalous pancreatobiliary junction and choledochal cyst is being increasingly recognized. We describe here the ERCP findings in three patients who had this anomaly in association with fusiform (Type I) choledochal cyst. Two of our patients also had evidence of pancreatitis. The importance of ERCP in the preoperative assessment of such patients is highlighted. PMID- 1885496 TI - Acute Budd-Chiari syndrome. PMID- 1885497 TI - Streptococcus, ASO titre, coxsackie virus and rheumatic fever. PMID- 1885498 TI - A case of acute reversible opsoclonus-myoclonus syndrome. PMID- 1885499 TI - AIDS and autopsy. PMID- 1885500 TI - Delhi prostitutes pose no additional threat of HBV transmission. PMID- 1885501 TI - Pulmonary hypertension in systemic lupus erythematosus. PMID- 1885502 TI - Priapism in leukaemia. PMID- 1885503 TI - Xipamide induced symptomatic severe hyponatraemia. PMID- 1885504 TI - Endoscopic removal of sewing needles from the stomach and duodenum using conventional biopsy forceps. PMID- 1885505 TI - Pain chest as a presentation of post operative recurrent ulcer. PMID- 1885506 TI - Locations of the zwf, edd, and eda genes on the Escherichia coli physical map. PMID- 1885507 TI - Physical map location of the asc (formerly sac) operon of Escherichia coli K-12. PMID- 1885508 TI - Physical map location of the Escherichia coli gene encoding the bifunctional enzyme 5,10-methylene-tetrahydrofolate dehydrogenase/5,10-methenyl tetrahydrofolate cyclohydrolase. PMID- 1885509 TI - Location of a new gene, greA, on the Escherichia coli chromosome. PMID- 1885510 TI - Isolation, sequence, and expression in Escherichia coli of the Pseudomonas sp. strain ACP gene encoding 1-aminocyclopropane-1-carboxylate deaminase. AB - Pseudomonas sp. strain ACP is capable of growth on 1-aminocyclopropane-1 carboxylate (ACC) as a nitrogen source owing to induction of the enzyme ACC deaminase and the subsequent conversion of ACC to alpha-ketobutyrate and ammonia (M. Honma, Agric. Biol. Chem. 49:567-571, 1985). The complete amino acid sequence of purified ACC deaminase was determined, and the sequence information was used to clone the ACC deaminase gene from a 6-kb EcoRI fragment of Pseudomonas sp. strain ACP DNA. DNA sequence analysis of an EcoRI-PstI subclone demonstrated an open reading frame (ORF) encoding a polypeptide with a deduced amino acid sequence identical to the protein sequence determined chemically and a predicted molecular mass of 36,674 Da. The ORF also contained an additional 72 bp of upstream sequence not predicted by the amino acid sequence. Escherichia coli minicells containing the 6-kb clone expressed a major polypeptide of the size expected for ACC deaminase which was reactive with ACC deaminase antiserum. Furthermore, a lacZ fusion with the ACC deaminase ORF resulted in the expression of active enzyme in E. coli. ACC is a key intermediate in the biosynthesis of ethylene in plants, and the use of the ACC deaminase gene to manipulate this pathway is discussed. PMID- 1885511 TI - Characterization and comparative sequence analysis of replication origins from three large Bacillus thuringiensis plasmids. AB - The replication origins of three large Bacillus thuringiensis plasmids, derived from B. thuringiensis HD263 subsp. kurstaki, have been cloned in Escherichia coli and sequenced. The replication origins, designated ori 43, ori 44, and ori 60, were isolated from plasmids of 43, 44, and 60 MDa, respectively. Each cloned replication origin exhibits incompatibility with the resident B. thuringiensis plasmid from which it was derived. Recombinant plasmids containing the three replication origins varied in their ability to transform strains of B. thuringiensis, Bacillus megaterium, and Bacillus subtilis. Analysis of the derived nucleotide and amino acid sequences indicates that the replication origins are nonhomologous, implying independent derivations. No significant homology was found to published sequences of replication origins derived from the single-stranded DNA plasmids of gram-positive bacteria, and shuttle vectors containing the three replication origins do not appear to generate single stranded DNA intermediates in B. thuringiensis. The replication origin regions of the large plasmids are each characterized by a single open reading frame whose product is essential for replication in B. thuringiensis. The putative replication protein of ori 60 exhibits partial homology to the RepA protein of the Bacillus stearothermophilus plasmid pTB19. The putative replication protein of ori 43 exhibits weak but extensive homology to the replication proteins of several streptococcal plasmids, including the open reading frame E replication protein of the conjugative plasmid pAM beta 1. The nucleotide sequence of ori 44 and the amino acid sequence of its putative replication protein appear to be nonhomologous to other published replication origin sequences. PMID- 1885513 TI - Construction of cloning cartridges for development of expression vectors in gram negative bacteria. AB - A cloning cartridge was constructed that can be inserted into a plasmid of choice to form an expression vector in which gene expression is inducible with an inexpensive inducer, sodium salicylate, at low concentrations. This cartridge consists of a 3.6-kb restriction fragment which contains the positive regulatory gene nahR from plasmid NAH7, a promoter, PG, that nahR regulates, a multiple cloning site, a transcription terminator, and a gene conferring tetracycline resistance. Within promoter PG of the cloning cartridge, a sequence of three nucleotides upstream of the ATG sequence encoding the initiation codon was altered to create an NdeI recognition site (CATATG) for cloning of the 5' end of a gene without affecting the distance between the transcription start site and the gene coding region. In addition, the 5' end of a gene can be converted into an NdeI recognition site without altering the amino acid sequence it encodes and then cloned into this cartridge for regulated expression. Several other synthetic restriction sites were also inserted downstream of the NdeI site for accepting the 3' end of a cloned gene. A derivative of this cloning cartridge lacking the NdeI sequence was also constructed for cloning and expression of a restriction fragment containing a gene(s) of unknown sequence. Use of the cloning cartridges in a broad-host-range plasmid has allowed successful cloning and inducible expression of several genes in all of the gram-negative bacterial tested to date. Protein production to at least 10% of the total soluble cell proteins was observed from a cloned gene expressed in Pseudomonas putida. PMID- 1885512 TI - Cloning and characterization of a Pseudomonas mendocina KR1 gene cluster encoding toluene-4-monooxygenase. AB - Pseudomonas mendocina KR1 metabolizes toluene as a carbon source by a previously unknown pathway. The initial step of the pathway is hydroxylation of toluene to form p-cresol by a multicomponent toluene-4-monooxygenase (T4MO) system. The T4MO enzyme system has broad substrate specificity and provides a new opportunity for biodegradation of toxic compounds and bioconversions. Its known activities include conversion of a variety of phenyl compounds into the phenolic derivatives and the complete degradation of trichloroethylene. We have cloned and characterized a gene cluster from KR1 that determines the offO activity. To clone the T4MO genes, KR1 DNA libraries were constructed in Escherichia coli HB101 by using a broad-host-range vector and transferred to a KR1 mutant able to grow on p cresol but not on toluene. An insert consisting of two SacI fragments of identical size (10.2 kb) was shown to complement the mutant for growth on toluene. One of the SacI fragments, when cloned into the E. coli vector pUC19, was found to direct the synthesis of indigo dye. The indigo-forming property was correlated with the presence of T4MO activity. The T4MO genes were mapped to a 3.6-kb region, and the direction of transcription was determined. DNA sequencing and N-terminal amino acid determination identified a five-gene cluster, tmoABCDE, within this region. Expression of this cluster carrying a single mutation in each gene demonstrated that each of the five genes is essential for T4MO activity. Other evidence presented indicated that none of the tmo genes was involved in the regulation of the tmo gene cluster, in the control of substrate transport for the T4MO system, or in major processing of the products of the tmo genes. It was tentatively concluded that the tmoABCDE genes encode structural polypeptides of the T4MO enzyme system. One of the tmo genes was tentatively identified as a ferredoxin gene. PMID- 1885515 TI - Cloning and expression in Escherichia coli of the structural gene coding for the monomeric protein of the S layer of Thermus thermophilus HB8. AB - The gene coding for the 100 kDa monomeric protein (P100) of the S layer of Thermus thermophilus HB8 has been cloned in the Escherichia coli plasmid vector pUC9. Recombinant plasmids were selected by colony screening with anti-P100 rabbit antiserum. The gene, named slpA (for surface layer protein A), was identified in a bacterial clone harboring a hybrid plasmid, pMF4, with a 5.8-kbp insert. This plasmid consistently expressed a protein specifically recognized by anti-P100 antiserum. Expression was apparently independent of Plac, indicating that the promoter for P100 is functional in E. coli. Most E. coli strains transformed with plasmids containing the 5.8-kbp insert cloned in pMF4 expressed two proteins with apparent masses of 52 and 50 kDa, which were strongly recognized by anti-P100 antiserum in Western immunoblots. The 52-kDa fragment could be overproduced, and the sequence of the N-terminal undecapeptide, determined by microsequencing, indicated that it could correspond to the N terminal domain of P100. Expression of slpA in lon mutants of E. coli led to accumulation of a protein indistinguishable from native P100, indicating that the complete gene was cloned and that the product of lon, protease La, was involved in proteolytic degradation of P100 synthesized in E. coli. PMID- 1885514 TI - Incorporation of light-harvesting complex I alpha and beta polypeptides into the intracytoplasmic membrane of Rhodobacter capsulatus. AB - The light-harvesting complex I (LHI) of Rhodobacter capsulatus is an oligomer of basic subunits each consisting of the two different pigment-binding polypeptides LHI alpha and LHI beta, encoded by the pufA (LHI alpha) and pufB (LHI beta) genes. Pulse-labeling experiments showed that in the presence of the LHI alpha polypeptide, the LHI beta polypeptide was inserted earlier into the intracytoplasmic membrane than was the LHI alpha polypeptide. Each of the pufA and pufB genes was deleted to test whether the LHI alpha and beta polypeptides, respectively, are inserted into the intracytoplasmic membrane independently of the LHI partner polypeptide. Neither deletion mutant strain formed the LHI antenna, but a functional reaction center complex was present. Pulse-labeling experiments indicated that the LHI beta polypeptide was inserted into the intracytoplasmic membrane with the same kinetics and in the same amounts regardless of whether the LHI alpha polypeptide was present. However, the LHI beta polypeptide did not accumulate in the membrane in the absence of the LHI alpha protein but was degraded linearly within about 12 min. In contrast to the LHI beta protein, only trace amounts of the LHI alpha polypeptide were inserted into or attached to the membrane if the LHI beta polypeptide was not synthesized. PMID- 1885516 TI - An unusual symbiont from the gut of surgeonfishes may be the largest known prokaryote. AB - Symbionts first reported from the gut of a Red Sea surgeonfish, Acanthurus nigrofuscus (family Acanthuridae), were subsequently described as Epulopiscium fishelsoni. The taxonomic position of this very large (up to 576 microns in length) microorganism has previously been designated in the literature as either uncertain or eukaryotic. We suggest that similar symbionts from Great Barrier Reef surgeonfish may be prokaryotes, which together with E. fishelsoni from the Red Sea may represent the largest known forms of this cell type. Features identifying the symbionts as prokaryotes include the presence of bacterial-type flagella and a bacterial nucleoid and the absence of a nucleus or any other membrane-bound organelle. PMID- 1885517 TI - Rhizobium lipopolysaccharide modulates infection thread development in white clover root hairs. AB - The interaction between Rhizobium lipopolysaccharide (LPS) and white clover roots was examined. The Limulus lysate assay indicated that Rhizobium leguminosarum bv. trifolii (hereafter called R. trifolii) released LPS into the external root environment of slide cultures. Immunofluorescence and immunoelectron microscopy showed that purified LPS from R. trifolii 0403 bound rapidly to root hair tips and infiltrated across the root hair wall. Infection thread formation in root hairs was promoted by preinoculation treatment of roots with R. trifolii LPS at a low dose (up to 5 micrograms per plant) but inhibited at a higher dose. This biological activity of LPS was restricted to the region of the root present at the time of exposure to LPS, higher with LPS from cells in the early stationary phase than in the mid-exponential phase, incubation time dependent, incapable of reversing inhibition of infection by NO3- or NH4+, and conserved among serologically distinct LPSs from several wild-type R. trifolii strains (0403, 2S 2, and ANU843). In contrast, infections were not increased by preinoculation treatment of roots with LPSs from R. leguminosarum bv. viciae strain 300, R. meliloti 102F28, or members of the family Enterobacteriaceae. Most infection threads developed successfully in root hairs pretreated with R. trifolii LPS, whereas many infections aborted near their origins and accumulated brown deposits if pretreated with LPS from R. meliloti 102F28. LPS from R. leguminosarum 300 also caused most infection threads to abort. Other specific responses of root hairs to infection-stimulating LPS from R. trifolii included acceleration of cytoplasmic streaming and production of novel proteins. Combined gas chromatography-mass spectroscopy and proton nuclear magnetic resonance analyses indicated that biologically active LPS from R. trifolii 0403 in the early stationary phase had less fucose but more 2-O-methylfucose, quinovosamine, 3,6 dideoxy-3-(methylamino)galactose, and noncarbohydrate substituents (O-methyl, N methyl, and acetyl groups) on glycosyl components than did inactive LPS in the mid-exponential phase. We conclude that LPS-root hair interactions trigger metabolic events that have a significant impact on successful development of infection threads in this Rhizobium-legume symbiosis. PMID- 1885518 TI - Nucleotide sequences of the Acinetobacter calcoaceticus benABC genes for benzoate 1,2-dioxygenase reveal evolutionary relationships among multicomponent oxygenases. AB - The nucleotide sequences of the Acinetobacter calcoaceticus benABC genes encoding a multicomponent oxygenase for the conversion of benzoate to a nonaromatic cis diol were determined. The enzyme, benzoate 1,2-dioxygenase, is composed of a hydroxylase component, encoded by benAB, and an electron transfer component, encoded by benC. Comparison of the deduced amino acid sequences of BenABC with related sequences, including those for the multicomponent toluate, toluene, benzene, and naphthalene 1,2-dioxygenases, indicated that the similarly sized subunits of the hydroxylase components were derived from a common ancestor. Conserved cysteine and histidine residues may bind a [2Fe-2S] Rieske-type cluster to the alpha-subunits of all the hydroxylases. Conserved histidines and tyrosines may coordinate a mononuclear Fe(II) ion. The less conserved beta-subunits of the hydroxylases may be responsible for determining substrate specificity. Each dioxygenase had either one or two electron transfer proteins. The electron transfer component of benzoate dioxygenase, encoded by benC, and the corresponding protein of the toluate 1,2-dioxygenase, encoded by xylZ, were each found to have an N-terminal region which resembled chloroplast-type ferredoxins and a C-terminal region which resembled several oxidoreductases. These BenC and XylZ proteins had regions similar to certain monooxygenase components but did not appear to be evolutionarily related to the two-protein electron transfer systems of the benzene, toluene, and naphthalene 1,2-dioxygenases. Regions of possible NAD and flavin adenine dinucleotide binding were identified. PMID- 1885520 TI - Effects of homocitrate, homocitrate lactone, and fluorohomocitrate on nitrogenase in NifV- mutants of Azotobacter vinelandii. AB - Azotobacter vinelandii DJ71, which contains a mutation in the nifV gene, was derepressed for nitrogenase in the presence of homocitrate. When dinitrogenase was isolated from this culture, it was found to be identical to the wild-type dinitrogenase. However, when the same NifV- strain was derepressed in the presence of erythrofluorohomocitrate, a homocitrate analog which produces a nitrogenase with wild-type properties in vitro, the isolated dinitrogenase was characteristic of the NifV- enzyme. These data show that homocitrate, but not fluorohomocitrate, is utilized by NifV- mutant cells. Fluorohomocitrate does not inhibit the uptake of homocitrate because the wild-type phenotype resulted when both compounds were added to the medium during nitrogenase derepression. Homocitrate lactone failed to cure the NifV- phenotype. PMID- 1885519 TI - Buoyant density studies of several mecillinam-resistant and division mutants of Escherichia coli. AB - The buoyant density of wild-type Escherichia coli cells has previously been reported not to vary with growth rate and cell size or age. In the present report we confirm these findings, using Percoll gradients, and analyze the recently described lov mutant, which was selected for its resistance to mecillinam and has been suggested to be affected in the coordination between mass growth and envelope synthesis. The average buoyant density of lov mutant cells was significantly lower than that of wild-type cells. Similarly, the buoyant density of wild-type cells decreased in the presence of mecillinam. The density of the lov mutant, like that of the wild type, was invariant over a 2.8-fold range in growth rate. In this range, however, the average cell volume was also constant. Analysis of buoyant density as a function of cell volume in individual cultures revealed that smaller (newborn) lov mutant cells had higher density than larger (old) cells; however, the density of the small cells never approached that of the wild-type cells, whose density was independent of cell size (age). A pattern similar to that of lov mutant cells was observed in cells carrying the mecillinam resistant mutations pbpA(Ts) and rodA(Ts) and the division mutation ftsI(Ts) at nonpermissive temperatures as well as in wild-type cells treated with mecillinam, but not in mecillinam-resistant crp or cya mutants. PMID- 1885521 TI - Molecular characterization of nosA, a Pseudomonas stutzeri gene encoding an outer membrane protein required to make copper-containing N2O reductase. AB - A Pseudomonas stutzeri gene (nosA) encoding an outer membrane protein was cloned into the broad-host-range vector pRK290 and expressed in a mutant lacking the protein. Deletion analysis identified the approximate extent of the nosA region which was sequenced, and it was found to contain an open reading frame encoding 683 amino acids including a presumed signal sequence of 44 amino acids. The putative processed form had a molecular weight of 70,218, characteristics typical of outer membrane proteins, and considerable amino acid sequence homology with Escherichia coli BtuB. A short stretch of amino acids was homologous with the E. coli TonB-dependent outer membrane proteins, BtuB, IutA, FepA, and FhuA, suggesting a homologous function: interaction with a periplasmic protein or uptake of a specific substrate. PMID- 1885522 TI - Cloning, mapping, and molecular characterization of the rRNA operons of Clostridium perfringens. AB - All 10 rRNA operons have been situated on the genome map of the anaerobic pathogen Clostridium perfringens. Four of these have been cloned and partially sequenced, and their transcriptional patterns in vivo and in vitro have been examined. Expression of rrnA, rrnB, and rrnE is directed by tandem promoters, P1 and P2, whereas rrnH is the only one to be expressed from a single promoter, which resembles P1. On inspection of the nucleotide sequences of the control regions, several sites which might be involved in the regulation of rrn expression were identified. These include a possible upstream activating region which could be recognized by the C. perfringens equivalent of the Escherichia coli Fis protein and a stringent response target site. Studies of maturation of 16S RNA identified two 5' cleavage sites and sequence analysis showed the dG+dC content of its gene, rrs, to be 52%, which is twice that of the genome. PMID- 1885523 TI - Acetate-dependent methylation of two corrinoid proteins in extracts of Methanosarcina barkeri. AB - Corrinoid proteins have been implicated as methyl carriers in methane formation from acetate, yet specific corrinoid proteins methylated by acetate-derived intermediates have not been identified. In the presence of ATP, H2, and bromoethanesulfonic acid, label from 3H- or 2-14C-labeled acetate was incorporated into the protein fraction of cell extracts of Methanosarcina barkeri. Incorporated label was susceptible to photolysis, yielding labeled methane as the anaerobic photolysis product. Size exclusion high-pressure liquid chromatography (HPLC) demonstrated the presence of at least three labeled proteins with native molecular sizes of 480, 200, and 29 kDa, while electrophoresis indicated that four major labeled proteins were present. Dual label experiments demonstrated that these four proteins were methylated rather than acetylated. Two of the proteins (480 and 29 kDa) contained the majority of radiolabel and were stably methylated. After labeling with [2-14C]acetate, the stable 14CH3-proteins were partially purified, and 14CH3-cofactors were isolated from each protein. UV-visible spectroscopy and HPLC demonstrated these to be methylated corrinoids. When the 480-kDa corrinoid protein was purified to 70% homogeneity, the preparation was found to have subunits of 40 and 30 kDa. The 480 kDa protein but not the 29-kDa protein was methylated during in vitro methanogenesis from acetate and demethylated as methanogenesis ceased, consistent with the involvement of this protein in methane formation. PMID- 1885525 TI - Phospholipids and a novel glycine-containing lipoamino acid in Cytophaga johnsonae Stanier strain C21. AB - Two-dimensional thin-layer chromatography revealed that Cytophaga johnsonae contains at least 10 kinds of lipid, 2 of which are phospholipids, namely, phosphatidylethanolamine and phosphatidylcholine. One of the remaining lipids is a novel lipid that contains an amino acid. The structure of this unusual lipid (lipoamino acid) was resolved by chemical and physicochemical methods. The fatty acyl moiety of this lipid was diverse. The structure of the major molecular species of the lipid was determined as iso-3-hydroxy heptadecanoic acid, amide linked to glycine and esterified to isopentadecanoic acid. This type of glycine containing lipid is a novel biological material which we have called cytolipin, basing this nomenclature on the genus of the bacterium. This is the first report of the lipid composition of C. johnsonae. PMID- 1885524 TI - Nucleotide sequence and genetic analysis of the Azotobacter chroococcum nifUSVWZM gene cluster, including a new gene (nifP) which encodes a serine acetyltransferase. AB - Nucleotide sequence was obtained for a region of 7,099 bp spanning the nifU, nifS, nifV, nifW, nifZ, and nifM genes from Azotobacter chroococcum. Chromosomal mutations constructed at several sites within the locus confirmed a requirement for this region for expression of the molybdenum nitrogenase in this organism. The genes are tightly clustered and ordered as in Klebsiella pneumoniae except for two additional open reading frames (ORFs) between nifV and nifW. The arrangement of genes in A. chroococcum closely matches that described for Azotobacter vinelandii. The polypeptide encoded by ORF4 immediately downstream from nifV is 41% identical over 186 amino acids to the product of the cysE gene from Escherichia coli, which encodes serine acetyltransferase (SAT), a key enzyme in cysteine biosynthesis. Plasmids which potentially express ORF4 complemented E. coli JM39, a cysteine auxotroph which lacks SAT. SAT activity was detected in crude extracts of one such complemented strain. A strain of A. chroococcum carrying a chromosomal disruption of ORF4 grew normally with ammonium as the N source but more slowly than the parental strain when N2 was the sole N source. These data suggest that ORF4 encodes a nif-specific SAT required for optimizing expression of nitrogenase activity. ORF4 was assigned the name nifP. nifP may be required to boost rates of synthesis or intracellular concentrations of cysteine or methionine. Sequence identity between nifV and leuA gene products suggests that nifV may catalyze a condensation reaction analogous to that carried out by isopropylmalate synthase (LEUA) but in which acetyl coenzyme and alpha ketoglutarate are substrates for the formation of homocitrate, the proposed product of NIFV activity. PMID- 1885526 TI - Purification and characterization of benzoate-coenzyme A ligase and 2 aminobenzoate-coenzyme A ligases from a denitrifying Pseudomonas sp. AB - The enzymes catalyzing the formation of coenzyme A (CoA) thioesters of benzoate and 2-aminobenzoate were studied in a denitrifying Pseudomonas sp. anaerobically grown with these aromatic acids and nitrate as sole carbon and energy sources. Three different rather specific aromatic acyl-CoA ligases, E1, E2, and E3, were found which catalyze the formation of CoA thioesters of benzoate, fluorobenzoates, and 2-aminobenzoate. ATP is cleaved into AMP and pyrophosphate. The enzymes were purified, their N-terminal amino acid sequences were determined, and their catalytic and molecular properties were studied. Cells anaerobically grown on benzoate and nitrate contain one CoA ligase (AMP forming) for benzoic acid (E1). It is a homodimer of Mr 120,000 which prefers benzoate as a substrate but shows some activity also with 2-aminobenzoate and fluorobenzoates, although with lower Km. Cells anaerobically grown on 2-aminobenzoate and nitrate contain three different CoA ligases for aromatic acids. The first one is identical with benzoate-CoA ligase (E1). The second enzyme is a 2-aminobenzoate-CoA ligase (E2). It is a monomer of Mr 60,000 which prefers 2-aminobenzoate but also activates benzoate, fluorobenzoates and, less effectively, 2-methylbenzoate, with lower affinities to the latter substrates. The enzymes E1 and E2 have similar activity levels; a third minor CoA ligase activity is due to a different 2-aminobenzoate CoA ligase. The enzyme (E3) is a monomer of Mr, 65,000 which 2-aminobenzoate pathway (U. Altenschmidt, C. Eckerskorn, and G. Fuchs, Eur. J. Biochem. 194:647 653, 1990); apparently, it is not completely repressed under anaerobic conditions and therefore also is induced to a small extent by 2-aminobenzoate under anaerobic growth conditions. PMID- 1885527 TI - Attenuated effect of oxygen on photopigment synthesis in Rhodospirillum centenum. AB - Rhodospirillum centenum resembles typical nonsulfur photosynthetic bacteria in a number of respects, including its ability to grow either anaerobically as a phototroph or aerobically as a heterotroph. We demonstrate, however, that R. centenum is unusual in its ability to synthesize a functional photosynthetic apparatus regardless of the presence of molecular oxygen. Aerobically expressed photopigments were shown to be functionally active, as demonstrated by the ability of heterotrophically grown cells to grow photosynthetically, without a lag, when suddenly placed under anaerobic conditions. An R. centenum mutant that has acquired the ability to repress synthesis of photopigments in the presence of oxygen was also characterized. Both the wild type and the oxygen-repressed mutant of R. centenum were found to exhibit high light intensity repression of photopigment biosynthesis. The latter result suggests that R. centenum contains separate regulatory circuits for controlling synthesis of its photochemical apparatus by light intensity and oxygen. PMID- 1885528 TI - Purification and characterization of Escherichia coli heat-stable enterotoxin II. AB - Escherichia coli heat-stable enterotoxin II (STII) was purified to homogeneity by successive column chromatographies from the culture supernatant of a strain harboring the plasmid encoding the STII gene. The purified STII evoked a secretory response in the suckling mouse assay and ligated rat intestinal loop assay in the presence of protease inhibitor, but the response was not observed in the absence of the inhibitor. Analyses of the peptide by the Edman degradation method and fast atom bombardment mass spectrometry revealed that purified STII is composed of 48 amino acid residues and that its amino acid sequence was identical to the 48 carboxy-terminal amino acids of STII predicted from the DNA sequence (C. H. Lee, S. L. Mosely, H. W. Moon, S. C. Whipp, C. L. Gyles, and M. So, Infect. Immun. 42:264-268, 1983). STII has four cysteine residues which form two intramolecular disulfide bonds. Two disulfide bonds were determined to be formed between Cys-10-Cys-48 and Cys-21-Cys-36 by analyzing tryptic hydrolysates of STII. PMID- 1885530 TI - An essential iteron-binding protein required for plasmid R1162 replication induces localized melting within the origin at a specific site in AT-rich DNA. AB - The R1162-encoded protein RepIB is essential for replication of the plasmid and binds specifically to iterons within the replicative origin. The protein causes the localized melting of DNA (determined by sensitivity to P1 nuclease) at a site within the AT-rich region of the origin, about 60 bp from the iteron binding sites and separated from them by a GC-rich tract. Point mutations have been isolated in the AT-rich DNA. These mutations interfere with origin activity and also prevent the protein-induced sensitivity to P1. A second-site suppressor of one of these mutations maps in the repIb gene and restores both origin function and sensitivity to P1. The results suggest a specific interaction between RepIB and origin DNA at a position distant from its primary binding site. PMID- 1885529 TI - A gene for a new lipoprotein in the dapA-purC interval of the Escherichia coli chromosome. AB - Cloning and sequence analysis of the region located downstream of the dapA gene of Escherichia coli has revealed the presence of an open reading frame that is cotranscribed with dapA. This gene codes for a 344-amino-acid polypeptide with a potential signal sequence characteristic of a lipoprotein. When this gene, called nlpB, is expressed from a multicopy plasmid in bacteria grown in the presence of [3H]palmitate, a labeled 37-kDa protein is produced. A slightly larger precursor molecule is detected when minicells expressing nlpB are treated with globomycin, a specific inhibitor of lipoprotein signal peptidase. Therefore, the nlpB gene encodes a new lipoprotein, designated NlpB. This lipoprotein is detected in outer membrane vesicles prepared from osmotically lysed spheroplasts and appears to be nonessential, since a strain in which the nlpB gene is disrupted by insertion of a chloramphenicol resistance gene is still able to grow and shows no discernible NlpB phenotype. The putative transcription termination signals of the dapA-nlpB operon overlap the promoter of the adjacent purC gene. PMID- 1885531 TI - Regulation of phenolic catabolism in Rhizobium leguminosarum biovar trifolii. AB - In members of the family Rhizobiaceae, many phenolic compounds are degraded by the protocatechuate branch of the beta-ketoadipate pathway. In this paper we describe a novel pattern of induction of protocatechuate (pca) genes in Rhizobium leguminosarum biovar trifolii. Isolation of pca mutant strains revealed that 4 hydroxybenzoate, quinate, and 4-coumarate are degraded via the protocatechuate pathway. At least three inducers govern catabolism of 4-hydroxybenzoate to succinyl coenzyme A and acetyl coenzyme A. The enzyme that catalyzes the initial step is induced by its substrate, whereas the catabolite beta-carboxy-cis,cis muconate induces enzymes for the upper protocatechuate pathway, and beta ketoadipate elicits expression of the enzyme for a subsequent step, beta ketoadipate succinyl-coenzyme A transferase. Elucidation of the induction pattern relied in part on complementation of mutant Rhizobium strains by known subclones of Acinetobacter genes expressed off the lac promoter in a broad-host-range vector. PMID- 1885532 TI - Analysis of Escherichia coli TonB membrane topology by use of PhoA fusions. AB - Alkaline phosphatase (PhoA) fusions to TonB amino acids 32, 60, 125, 207, and 239 (the carboxy terminus) all showed high PhoA activity; a PhoA fusion to TonB amino acid 12 was inactive. The full-length TonB-PhoA fusion protein was associated with the cytoplasmic membrane and retained partial TonB function. These results support a model in which TonB is anchored in the cytoplasmic membrane by its hydrophobic amino terminus, with the remainder of the protein, including its hydrophobic carboxy terminus, extending into the periplasm. PMID- 1885534 TI - A transducing bacteriophage for Caulobacter crescentus uses the paracrystalline surface layer protein as a receptor. AB - The bacteriophage phi Cr30, a transducing phage for Caulobacter crescentus strains, required the paracrystalline surface (S) layer for infectivity. Wild type strains were phage resistant when rsaA, the gene for the 130K S-layer protein, was interrupted with an antibiotic resistance cassette. Strains that had lost the S layer by mutation were phage resistant, as were mutants that produce an S layer but which do not attach the structure to the cell surface. Phage sensitivity was restored to 130K-protein-deficient strains by introducing rsaA on a plasmid. Spontaneous phage-resistant strains produced expected phenotypes as follows (in order of decreasing frequency): S-layer cell attachment defects, no S layer, or an S layer that was wild type in appearance. PMID- 1885533 TI - Stimulation of Agrobacterium tumefaciens T-DNA transfer by overdrive depends on a flanking sequence but not on helical position with respect to the border repeat. AB - T-DNA transfer by Agrobacterium tumefaciens depends on the right border repeat of the T-DNA and is greatly stimulated by overdrive, an adjacent sequence. We report that the function of overdrive does not depend on helical position with respect to the border repeat. A synthetic 24-bp overdrive and a 12-bp region containing a fully conserved 8-bp core overdrive sequence stimulated virulence equally, but full function required additional bases to the left of the 24-bp sequence. PMID- 1885535 TI - Elevation of superoxide dismutase in Halobacterium halobium by heat shock. AB - Exposure of Halobacterium halobium to 50 degrees C for 2.5 h in an aerobic environment resulted in a greater than twofold increase in the activity of the manganese-containing superoxide dismutase. Nondenaturing polyacrylamide gels stained for enzymatic activity did not reveal any additional isozymes of superoxide dismutase induced by the heat shock. The maximal effect was observed at 50 degrees C, and the elevated levels of activity remained constant during 5 h of recovery at 40 degrees C. The induction of enzymatic activity was sensitive to protein synthesis inhibitors. The results are discussed relative to heat shock and stress-related proteins as well as alterations in metabolism brought about by elevated temperatures. PMID- 1885536 TI - Analysis of outer membrane ultrastructure of pathogenic Treponema and Borrelia species by freeze-fracture electron microscopy. AB - We analyzed the outer membrane (OM) ultrastructure of four pathogenic members of the family Spirochaetaceae by freeze fracture. The OM of Treponema pallidum subsp. pertenue contained a low intramembranous particle concentration, indicating that it contains few OM transmembrane proteins. The concave OM fracture faces of Treponema hyodysenteriae and Borrelia burgdorferi contained dense populations of particles, typical of gram-negative organisms. A relatively low concentration of particles which were evenly divided between a small and a large species was present in the concave OM fracture face of Borrelia hermsii; the convex OM fracture face contained only small particles. As for gram-negative bacteria, the convex OM fracture face particle concentrations of these pathogens were low. These spirochetes cleaved preferentially within the OM, in contrast to typical gram-negative bacteria, which tend to fracture within the inner membrane. The OM ultrastructure of T. pallidum subsp. pertenue provides an explanation for the lack of antigenicity of the treponemal surface and may reflect a mechanism by which this pathogen evades the host immune response. PMID- 1885537 TI - Escherichia coli orfE (upstream of pyrE) encodes RNase PH. AB - RNase PH from extracts of Escherichia coli was purified to homogeneity and subjected to NH2-terminal sequencing. Comparison of this sequence with all open reading frames in the GenBank data base revealed at least 95% identity to an unidentified open reading frame (orfE) upstream of pyrE at 81.7 min on the E. coli chromosome. Clones of orfE overexpress RNase PH activity, verifying that orfE encodes this ribonuclease. We suggest that orfE be renamed rph. PMID- 1885538 TI - Content and composition of hopanoids in Zymomonas mobilis under various growth conditions. AB - By using a new method for quantification of the different hopanoid derivatives, a total hopanoid content of about 30 mg/g (dry cell weight) was observed in Zymomonas mobilis. This value is the highest reported for bacteria so far. The major hopanoids in Z. mobilis were the ether and glycosidic derivatives of tetrahydroxy-bacteriohopane, constituting about 41 and 49% of the total hopanoids. Tetrahydroxybacteriohopane itself, diplopterol, and hopene made up about 6, 3, and 1%, respectively. Only minor changes in hopanoid composition were observed with changes in growth conditions. Earlier reports on a correlation between hopanoid content and ethanol concentration in the medium could not be confirmed. Over a wide range of ethanol concentrations (5 to 60 g/liter), growth rates (0.08 to 0.25 h-1), and temperatures (25 to 37 degrees C), the molar ratio of hopanoids to phospholipids in the cells amounted to about 0.7. Only at growth rates of greater than 0.30 h-1 did the molar ratio increase to about 1. PMID- 1885539 TI - Cloning, nucleotide sequence, and expression of the Pasteurella haemolytica A1 glycoprotease gene. AB - Pasteurella haemolytica serotype A1 secretes a glycoprotease which is specific for O-sialoglycoproteins such as glycophorin A. The gene encoding the glycoprotease enzyme has been cloned in the recombinant plasmid pH1, and its nucleotide sequence has been determined. The gene (designated gcp) codes for a protein of 35.2 kDa, and an active enzyme protein of this molecular mass can be observed in Escherichia coli clones carrying pPH1. In vivo labeling of plasmid encoded proteins in E. coli maxicells demonstrated the expression of a 35-kDa protein from pPH1. The amino-terminal sequence of the heterologously expressed protein corresponds to that predicted from the nucleotide sequence. The glycoprotease is a neutral metalloprotease, and the predicted amino acid sequence of the glycoprotease contains a putative zinc-binding site. The gene shows no significant homology with the genes for other proteases of procaryotic or eucaryotic origin. However, there is substantial homology between gcp and an E. coli gene, orfX, whose product is believed to function in the regulation of macromolecule biosynthesis. PMID- 1885540 TI - Mutagenic DNA repair in enterobacteria. AB - Sixteen species of enterobacteria have been screened for mutagenic DNA repair activity. In Escherichia coli, mutagenic DNA repair is encoded by the umuDC operon. Synthesis of UmuD and UmuC proteins is induced as part of the SOS response to DNA damage, and after induction, the UmuD protein undergoes an autocatalytic cleavage to produce the carboxy-terminal UmuD' fragment needed for induced mutagenesis. The presence of a similar system in other species was examined by using a combined approach of inducible-mutagenesis assays, cross reactivity to E. coli UmuD and UmuD' antibodies to test for induction and cleavage of UmuD-like proteins, and hybridization with E. coli and Salmonella typhimurium umu DNA probes to map umu-like genes. The results indicate a more widespread distribution of mutagenic DNA repair in other species than was previously thought. They also show that umu loci can be more complex in other species than in E. coli. Differences in UV-induced mutability of more than 200 fold were seen between different species of enteric bacteria and even between multiple natural isolates of E. coli, and yet some of the species which display a poorly mutable phenotype still have umu-like genes and proteins. It is suggested that umDC genes can be curtailed in their mutagenic activities but that they may still participate in some other, unknown process which provides the continued stimulus for their retention. PMID- 1885541 TI - Deletions or duplications in the BtuB protein affect its level in the outer membrane of Escherichia coli. AB - The Escherichia coli btuB product is an outer membrane protein that mediates the TonB-coupled active transport of cobalamins and the uptake of the E colicins and bacteriophage BF23. The roles of various segments of the BtuB protein in its function or cellular localization were investigated by analysis of several genetic constructs. Hybrid proteins in which various lengths from the amino terminus of BtuB were linked to alkaline phosphatase (btuB::phoA genes) were all secreted across the cytoplasmic membrane. The BtuB-PhoA proteins that carried up to 327 amino acids of BtuB appeared to reside in the periplasmic space, whereas hybrid proteins containing at least 399 amino acids of BtuB were associated with the outer membrane. Eleven in-frame internal deletion mutations that spanned more than half of the mature sequence were prepared by combining appropriate restriction fragments from btuB variants with 6-bp linker insertions. None of the deleted proteins was able to complement any BtuB functions, and only three of them were detectable in the outer membrane, suggesting that most of the deletions affected sequences needed for stable association with the outer membrane. Duplications covering the same portions of BtuB were prepared in the same manner. All of these partial duplication variants complemented all BtuB functions, although some gave substantially reduced levels of activity. These proteins were found in the outer membrane, although some were subject to proteolytic cleavage within or near the duplicated segment. These results indicate that the insertion of BtuB into the outer membrane requires the presence of several regions of teh BtuB protein and that the presence of extra or redundant segments of the protein can be tolerated during its insertion and function. PMID- 1885542 TI - Arc and Sfr functions of the Escherichia coli K-12 arcA gene product are genetically and physiologically separable. AB - The Escherichia coli arcA gene product regulates chromosomal gene expression in response to deprivation of oxygen (Arc function; Arc stands for aerobic respiration control) and is required for expression of the F plasmid DNA transfer (tra) genes (Sfr function; Sfr stands for sex factor regulation). Using appropriate lacZ fusions, we have examined the relationship between these two genetic regulatory functions. Arc function in vivo was measured by anaerobic repression of a chromosomal sdh-lacZ operon fusion (sdh stands for succinate dehydrogenase). Sfr function was measured by activation of a plasmid traY-lacZ gene fusion. An eight-codon insertion near the 5' terminus of arcA, designated arcA1, abolished Arc function, as previously reported by S. Iuchi and E.C.C. Lin (Proc. Natl. Acad. Sci. USA 85:1888-1892, 1988), but left Sfr function largely (greater than or equal to 60%) intact. Similarly, the arcB1 mutation, which depressed sdh expression and is thought to act by abolishing the signal input that elicits ArcA function, had little effect (less than or equal to 20%) on the Sfr function of the arcA+ gene product. Conversely, a valine-to-methionine mutation at codon 203 (the sfrA5 allele) essentially abolished Sfr activity without detectably altering Arc activity. These data indicate that Sfr and Arc functions are separately expressed and regulated properties of the same protein. PMID- 1885543 TI - Macromolecular structure and aggregation states of Helicobacter pylori urease. AB - Urease purified from Helicobacter pylori by differential ultracentrifugation and fast pressure liquid chromatography was composed of subunits with apparent molecular weights (MrS) of 66,000 and 30,000. Electron microscopy of this purified material demonstrated that it formed disc-shaped macromolecular aggregates that were approximately 13 nm in diameter and 3 nm thick. Images of both negatively stained and shadowed preparations indicated that the discs tended to stack to form pairs and then these pairs further aggregated to form four-disc stacks. This stacking of subunits explains the heterogeneity observed previously in the molecular weight of urease preparations. In some negatively stained preparations there were also some smaller (approximately 8-nm-diameter) annular units present, which may represent individual urease units or possibly an aggregate of one of the two subunits from which urease is constructed. PMID- 1885544 TI - Subcellular distribution of the soluble lytic transglycosylase in Escherichia coli. AB - The localization of the major autolytic enzyme, the soluble lytic transglycosylase, in the different cell compartments of Escherichia coli was investigated by immunoelectron microscopy. Ultrathin sections were labeled with a specific antiserum against purified soluble lytic transglycosylase, and the antibody-enzyme complexes were visualized with colloidal protein A-gold. A preferential localization of the lytic transglycosylase in the envelope was observed, with only 20 to 30% of the enzyme left in the cytoplasm. Most of the enzyme associated with the cell wall was tightly bound to the murein sacculus. Sacculi prepared by boiling of cells in 4% sodium dodecyl sulfate could be immunolabeled with the specific antiserum, indicating a surprisingly strong interaction of the lytic transglycosylase with murein. The enzyme-substrate complex could be reconstituted in vitro by incubating pronase-treated, protein free murein sacculi with purified lytic transglycosylase at 0 degrees C. Titration of sacculi with increasing amounts of enzyme indicated a limiting number of binding sites for about 1,000 molecules of enzyme per sacculus. Ruptured murein sacculi obtained after penicillin treatment revealed that the enzyme is exclusively bound to the outer surface of the sacculus. This finding is discussed in the light of recent evidence suggesting that the murein of E. coli might be a structure of more than one layer expanding by inside-to-outside growth of patches of murein. PMID- 1885545 TI - Identification, isolation, and structural studies of extracellular polysaccharides produced by Caulobacter crescentus. AB - Caulobacters are adherent prosthecate bacteria that are members of bacterial biofouling communities in many environments. Investigation of the cell surface carbohydrates produced by two strains of the freshwater Caulobacter crescentus, CB2A and CB15A, revealed a hitherto undetected extracellular polysaccharide (EPS) or capsule. Isolation and characterization of the EPS fractions showed that each strain produced a unique neutral EPS which could not be readily removed from the cell surface by washing. Monosaccharide analysis showed that the main CB2A EPS contained D-glucose, D-gulose, and D-fucose in a ratio of 3:1:1, whereas the CB15A EPS fraction contained D-galactose, D-glucose, D-mannose, and D-fucose in approximately equal amounts. Methylation analysis of the main CB2A EPS showed the presence of terminal glucose and gulose groups, 3-linked fucosyl, and two 3,4 linked glucosyl units, thus confirming the pentasaccharide repeating unit indicated by 1H nuclear magnetic resonance analysis. Similar studies of the CB15A EPS revealed a tetrasaccharide repeating unit consisting of terminal galactose, 4 linked fucosyl, 3-linked glucosyl, and 3,4-linked mannosyl residues. EPS was not detectable by thin-section electron microscopy techniques, including some methods designed to preserve or enhance capsules, nor was the EPS readily detected on the cell surface by scanning electron microscopy when conventional fixation techniques were used; however, a structure consistent with EPS was revealed when samples were prepared by cryofixation and freeze-substitution methods. PMID- 1885546 TI - Linkage distortion following conjugational transfer of sbcC+ to recBC sbcBC strains of Escherichia coli. AB - Conjugational recombination in Escherichia coli depends normally on RecBCD enzyme, a multifunctional nuclease and DNA helicase produced by the recB, recC, and recD genes. However, recombination can proceed efficiently without RecBCD in recB or recC strains carrying additional mutations in both the sbcB and sbcC genes. Recombination in these strains, sometimes referred to as the RecF pathway, requires gene products that are not essential in the RecBCD-dependent process predominating in the wild type. It has also been reported to produce a different spectrum of recombinant genotypes in crosses with Hfr donors. However, the sbcC+ gene was unknowingly transferred to the recipient strain in some of these crosses, and this may have affected the outcome. This possibility was examined by conducting parallel crosses with Hfr donors that were either wild type or mutant for sbcC. Transfer of sbcC+ from an Hfr donor is shown to alter the frequency of recombinant genotypes recovered. There is a severe reduction in progeny that inherit donor markers linked to the sbcC+ allele and an increase in the incidence of multiple exchanges. Colonies of mixed genotype for one or more of the unselected proximal markers are also much more prevalent. Since the yield of recombinants is lower than normal, these changes are attributed to the reduced viability of recombinants that inherit sbcC+ from the Hfr donor. When the Hfr donor used is also mutant for sbcC, the yield of recombinants is greater and the frequencies of the different genotypes recovered are similar to those obtained in crosses with a rec+ sbc+ recipient, in which transfer of sbcC+ has no apparent effect. Earlier studies are re-examined in light of these findings. It is concluded that, while recombination in recBC sbcBC strains involves different enzymes, the underlying molecular mechanism is essentially the same as that in the wild type. PMID- 1885547 TI - Penicillin-binding protein 1B of Escherichia coli exists in dimeric forms. AB - A high-molecular-weight band has been detected in Western immunoblots of nonboiled Escherichia coli samples incubated with polyclonal antiserum against penicillin-binding protein 1B (PBP 1B). This band was shown to be a dimer of PBP 1B. The dimer was more strongly associated with the envelope than the monomer, and it was still able to bind penicillin G. Analysis of the binding of fusion proteins of PBP 1B and beta-lactamase showed that the part of PBP 1B necessary for complex formation lies in the amino-terminal half of the protein. PMID- 1885548 TI - Molecular analysis of the Escherichia coli ruvC gene, which encodes a Holliday junction-specific endonuclease. AB - The Escherichia coli ruvC gene is involved in DNA repair and recombination and encodes an endonuclease that resolves Holliday structure in vitro. The 2.8-kb chromosomal DNA fragment that encompasses the ruvC gene and its flanking regions was cloned and sequenced. Four open reading frames were identified in the order orf17-orf26-ruvC-orf23 immediately upstream of the ruvAB operon, and their orientations are the same as the ruvAB operon, except for orf23. Proteins encoded by orf17, orf26, and ruvC (orf19) were identified by the maxicell method, and their sizes agreed with those predicted from the DNA sequences. Among the open reading frames in this region, only ruvC is involved in the repair of UV-damaged DNA. ruvC appeared to be regulated by at least two promoters, but, in contrast to the ruvAB operon, ruvC is not regulated by the SOS system as demonstrated by operon fusions. PMID- 1885549 TI - Identification of the Escherichia coli sohB gene, a multicopy suppressor of the HtrA (DegP) null phenotype. AB - We cloned and sequenced the sohB gene of Escherichia coli. The temperature sensitive phenotype of bacteria that carry a Tn10 insertion in the htrA (degP) gene is relieved when the sohB gene is present in the cell on a multicopy plasmid (30 to 50 copies per cell). The htrA gene encodes a periplasmic protease required for bacterial viability only at high temperature, i.e., above 39 degrees C. The sohB gene maps to 28 min on the E. coli chromosome, precisely between the topA and btuR genes. The gene encodes a 39,000-Mr precursor protein which is processed to a 37,000-Mr mature form. Sequencing of a DNA fragment containing the gene revealed an open reading frame which could encode a protein of Mr 39,474 with a predicted signal sequence cleavage site between amino acids 22 and 23. Cleavage at this site would reduce the size of the processed protein to 37,474 Mr. The predicted protein encoded by the open reading frame has homology with the inner membrane enzyme protease IV of E. coli, which digests cleaved signal peptides. Therefore, it is possible that the sohB gene encodes a previously undiscovered periplasmic protease in E. coli that, when overexpressed, can partially compensate for the missing HtrA protein function. PMID- 1885550 TI - Plant signal molecules activate the syrB gene, which is required for syringomycin production by Pseudomonas syringae pv. syringae. AB - The syrB gene is required for syringomycin production by Pseudomonas syringae pv. syringae and full virulence during plant pathogenesis. Strain B3AR132 containing a syrB::lacZ fusion was used to detect transcriptional activation of the syrB gene in syringomycin minimal medium by plant metabolites with signal activity. Among 34 plant phenolic compounds tested, arbutin, phenyl-beta-D-glucopyranoside, and salicin were shown to be strong inducers of syrB, giving rise to approximately 1,200 U of beta-galactosidase activity at 100 microM; esculin and helicin were moderate inducers, with about 250 to 400 U of beta-galactosidase activity at 100 microM. Acetosyringone and flavonoids that serve as signal molecules in Agrobacterium and Rhizobium species, respectively, did not induce the syrB::lacZ fusion. All syrB inducers were phenolic glucosides and none of the aglucone derivatives were active, suggesting that the beta-glycosidic linkage was necessary for signal activity. Phenyl-beta-D-galactopyranoside containing galactose substituted for glucose in the beta-glycosidic linkage also lacked inducer activity. Phenolic signal activity was enhanced two- to fivefold by specific sugars common to plant tissues, including D-fructose, D-mannose, and sucrose. The effect of sugars on syrB induction was most noticeable at low concentrations of phenolic glucoside (i.e., 1 to 10 microM), indicating that sugars such as D-fructose increase the sensitivity of P. syringae pv. syringae to the phenolic plant signal. Besides induction of syrB, syringomycin biosynthesis by parental strain B3A-R was induced to yield over 250 U of toxin by the additions of arbutin and D-fructose to syringomycin minimal medium. These data indicate that syringomycin production by most strains of P. syringae pv. syringae is modulated by the perception of two classes of plant signal molecules and transduced to the transcriptional apparatus of syringomycin (syr) genes such as syrB. PMID- 1885551 TI - Integration host factor binds specifically to multiple sites in the ompB promoter of Escherichia coli and inhibits transcription. AB - Escherichia coli integration host factor (IHF) is a DNA-binding protein that participates in gene regulation, site-specific recombination, and other processes in E. coli and some of its bacteriophages and plasmids. In the present study, we showed that IHF is a direct negative effector of the ompB operon of E. coli. Gel retardation experiments and DNase I footprinting studies revealed that IHF binds to three sites in the ompB promoter region. In vitro transcription from ompB promoter fragments was specifically blocked by IHF. In vivo experiments showed that IHF is a negative effector of ompB expression in growing cells. Analysis of IHF binding site mutations strongly suggested that IHF binding in the ompB promoter region is necessary for the negative effects seen in vivo. PMID- 1885552 TI - Mutations that affect activity of the Rhizobium meliloti trpE(G) promoter in Rhizobium meliloti and Escherichia coli. AB - The cloned Rhizobium meliloti trpE(G) gene is not expressed in Escherichia coli. Oligonucleotide-directed mutagenesis was used to introduce base substitution mutations in the promoter region of this gene. Three separate mutations that increased homology of the putative -10 region of this promoter with the E. coli 10 promoter consensus sequence by 1 bp converted this promoter to an active promoter in E. coli. A deletion extending to position -43 from the 5' side had a minor effect on transcription in R. meliloti. However, transcription was nearly eliminated when a deletion extended to position -33, indicating that the crucial domain of the R. meliloti trpE(G) promoter begins in the region downstream of position -43. The R. meliloti trpE(G) promoter has two regions that show homology with the E. coli -35 and -10 promoter consensus sequences. Mutations in these putative -35 and -10 regions, but not in the spacer region, affected promoter strength in R. meliloti. By comparing four known R. meliloti promoter sequences, we identified a highly conserved trimer near position -35 (5'-TTG-3') but no noticeably conserved sequence near position -10. PMID- 1885553 TI - Broad-host-range properties of plasmid RK2: importance of overlapping genes encoding the plasmid replication initiation protein TrfA. AB - The trfA gene, encoding the essential replication initiation protein of the broad host-range plasmid RK2, possesses an in-frame overlapping arrangement. This results in the production of TrfA proteins of 33 and 44 kDa, respectively. Utilizing deletion and site-specific mutagenesis to alter the trfA operon, we compared the replication of an RK2-origin plasmid in several distantly related gram-negative bacteria when supported by both TrfA-44 and TrfA-33, TrfA-33 alone, or TrfA-44/98L (a mutant form of the TrfA-44 protein) alone. TrfA-44/98L is identical to wild-type TrfA-44 with the exception of a single conservative amino acid alteration from methionine to leucine at codon 98; this alteration removes the translational start codon for the TrfA-33 protein. Copy number and stability were virtually identical for plasmids containing both TrfA-44 and TrfA-33 proteins or TrfA-44/98L alone in Pseudomonas aeruginosa and Agrobacterium tumefaciens, two unrelated bacteria in which TrfA-33 is poorly functional. This, along with recent in vitro studies comparing TrfA-44, TrfA-33, and TrfA-44/98L, suggests that the functional activity of TrfA-44 is not significantly affected by the 98L mutation. Analysis of minimal RK2 derivatives in certain gram-negative bacterial hosts suggests a role of the overlapping arrangement of trfA in facilitating the broad host range of RK2. RK2 derivatives encoding TrfA-44/98L alone demonstrated decreased copy number and stability in Escherichia coli and Azotobacter vinelandii when compared with derivatives specifying both TrfA-44 and TrfA-33. A strategy employing the trfA-44/98L mutant gene and in vivo homologous recombination was used to eliminate the internal translational start codon of trfA in the intact RK2 plasmid. The mutant intact RK2 plasmid produced only TrfA 44/98L. A small reduction in copy number and beta-lactamase expression resulted in E. coli, suggesting that overlapping trfA genes also enhance the efficiency of replication of the intact RK2 plasmid. PMID- 1885554 TI - Mutations in trans that affect formate dehydrogenase (fdhF) gene expression in Salmonella typhimurium. AB - Expression of the fdhF locus of Salmonella typhimurium is shown to be dependent upon ntrA and oxrB. However, the oxrB8 mutation is pleiotropic and also affects the expression of hyd, pepT, and chlC, whereas a mutation in ntrA does not. Insertional inactivation with Tn10 and localized mutagenesis permitted the definition and partial characterization of two new genes, fdhS and fdhR, which appear to be involved in the positive regulation of fdhF expression. Both genes were mapped to the 71- to 72-min region of the S. typhimurium chromosome with the gene order fdhS-crp-fdhR-rpsL. Mutations in fdhS specifically affect fdhF expression without affecting the expression of the other anaerobically induced genes or enzymes that were tested, including hyd, pepT, chlC, nitrite reductase, sulfite reductase, and trimethylamine-N-oxide reductase. Both fdhR and fdhS may be involved in fdhF regulation vis-a-vis oxygen, since localized mutagenesis produced alleles of both genes that permitted the aerobic expression of fdhF. However, fdhR may more directly interact with fdhF, since insertional inactivation of fdhS does not abolish aerobic expression of fdhF in fdhR mutant strains. Taken together, these results suggest that fdhS and fdhR act in concert under anaerobic conditions to activate fdhF transcription. PMID- 1885555 TI - The small-subunit polypeptide of methylamine dehydrogenase from Methylobacterium extorquens AM1 has an unusual leader sequence. AB - The nucleotide sequence for the N-terminal region of the small subunit of methylamine dehydrogenase from Methylobacterium extorquens AM1 has revealed a leader sequence that is unusual in both its length and composition. Gene fusions to lacZ and phoA show that this leader sequence does not function in Escherichia coli but does function in M. extorquens AM1. PMID- 1885556 TI - In vitro activity of the nitrogen fixation regulatory protein FIXJ from Rhizobium meliloti. AB - Cell extracts of an Escherichia coli strain that overproduces the regulatory protein FIXJ from Rhizobium meliloti promoted transcription of fixK, a known FIXJ dependent gene, in a coupled transcription-translation assay. Activation by FIXJ was dependent on the sigma 70 holoenzyme form of RNA polymerase. PMID- 1885557 TI - Null mutants of Saccharomyces cerevisiae Cu,Zn superoxide dismutase: characterization and spontaneous mutation rates. AB - Deletion-replacement mutations of the Saccharomyces cerevisiae Cu,Zn superoxide dismutase gene were constructed. They were exquisitely sensitive to redox cycling drugs and showed slight sensitivity to other agents. The aerobic spontaneous mutation rate was three- to fourfold higher in sod1 delta 1 mutants, while the anaerobic rate was similar to that of the wild type. PMID- 1885558 TI - Plasmids in diatom species. AB - We have discovered plasmids in 5 of 18 diatom species surveyed. In several species, more than one type of plasmid is present. Several of the plasmids show similarity by hybridization previously characterized plasmids in Cylindrotheca fusiformis (J. D. Jacobs et al., unpublished data). Additionally, there is similarity between the plasmids found in C. fusiformis and chloroplast DNA in three diatom species. These results add to the evidence that the plasmids have features of mobile genetic elements. PMID- 1885560 TI - Secretion and lipid association of human apolipoprotein E in Saccharomyces cerevisiae requires a host mutation in sterol esterification and uptake. AB - We have expressed a cDNA to human apolipoprotein E (apoE) in Saccharomyces cerevisiae. Secretion of apoE was achieved only by the use of a mutant (upc2) strain of yeast with the phenotype of enhanced uptake and intracellular esterification of exogenous cholesterol. Approximately 40 ng/ml apoE was secreted by upc2 mutants in the absence of media cholesterol. ApoE secretion was increased 2-3-fold upon the inclusion of cholesterol in the growth media. This response to exogenous cholesterol was not mediated at the transcriptional level, since apoE mRNA levels were constant under all culture conditions. Concomitant with the increase in secretion following cholesterol uptake by upc2 strains, approximately 5% of secreted apoE was associated with lipid; polar and non-polar lipids were detected in this lipoprotein fraction. Intracellular degradation of apoE in non secreting strains of yeast was minimized by the presence of null mutations in both vacuolar proteases with non-specific activity (pep4) and a Golgi endopeptidase with specificity for paired basic residues (kex2). The approach of expressing human apolipoproteins in yeast may identify factors that mediate lipoprotein biosynthesis in higher cells. One such factor could be the mammalian equivalent of the gene product of UPC2. PMID- 1885559 TI - Identification and sequence analysis of the hupR1 gene, which encodes a response regulator of the NtrC family required for hydrogenase expression in Rhodobacter capsulatus. AB - The hupR1 gene from Rhodobacter capsulatus was cloned and sequenced. It can encode a protein of 53,843 Da which shares significant similarity with several transcriptional regulators and activates transcription of the structural hupSL genes of [NiFe]hydrogenase, as shown by the use of a translational fusion of lacZ with the hupSL promoter. A Hup- mutant having a point mutation in the hupR1 gene is described. PMID- 1885561 TI - T4 phage ribonucleotide reductase. Allosteric regulation in vivo by thymidine triphosphate. AB - Based upon analyses of purified enzyme preparations, T4 bacteriophage-coded ribonucleotide reductase is considered to be relatively insensitive to control by allosteric inhibition. However, two factors suggest that CDP reduction to dCDP is feedback-controlled by dTTP in infected cells. First, the pool of 5 hydroxymethyldeoxycytidine triphosphate, which expands manyfold upon infection by a dCMP deaminase-deficient T4 mutant, shrinks to near-normal levels as a consequence of dTTP accumulation, and ribonucleotide reductase is the only apparent control point. Second, analysis of mutagenesis by 5-bromodeoxyuridine suggests that most induced mutations result from localized pool depletion of 5 hydroxymethyl-dCTP at replication sites, as if 5-bromo-dUTP were behaving like dTTP in inhibiting the CDP reductase activity of the phage enzyme. We found that CDP reductase activity in crude extracts of T4 phage-infected bacteria is sensitive to inhibition by either dTTP or 5-bromo-dUTP, at concentrations as low as 0.01 mM. However, in partially purified enzyme preparations that sensitivity is lost. Although we don't know the basis for this loss of feedback sensitivity, the results suggest that kinetic properties of enzymes in intact cells are determined by the cellular milieu in ways not apparent from analysis of purified enzymes. PMID- 1885562 TI - Binding protein-independent histidine permease mutants. Uncoupling of ATP hydrolysis from transmembrane signaling. AB - Periplasmic permeases consist of a substrate-binding receptor, located in the periplasm, and a membrane-bound complex composed of two integral membrane proteins and two nucleotide-binding proteins. The receptor interacts with the membrane-bound complex, which, upon receiving this signal, is postulated to hydrolyze ATP and translocate the substrate. We show that a class of mutations in the membrane-bound complex of the histidine permease, which allow transport in the absence of the substrate-binding protein, hydrolyze ATP independently from any signal. The data are compatible with the notion that cross-membrane signaling between the liganded periplasmic receptor and the cytoplasmic ATP-binding sites initiates conformational changes leading to ATP hydrolysis and substrate translocation. PMID- 1885563 TI - Wide distribution of the variant form of the human malaria parasite Plasmodium vivax. AB - We have found polymorphism in the repetitive and nonrepetitive regions of the sporozoite vaccine antigen, the circumsporozoite (CS) protein, in Plasmodium vivax malaria parasites from two geographically distant malaria endemic regions of the world. Like the recently described variant repeat sequence of P. vivax from Thailand, the CS protein repeat sequence of the variant P. vivax parasites from Papua New Guinea and Brazil is ANGA(G/D)(N/D)QPG, which differs from the previously identified CS repeat sequence, GDRA(D/A)GQPA, of P. vivax parasites from South America, Central America, and North Korea. Comparison of the P. vivax CS protein outside the repeat region revealed restricted polymorphism in regions that have exhibited T-cell immune function and sequence heterogeneity in the CS protein of Plasmodium falciparum. Our results show that P. vivax malaria parasites with the variant CS repeat sequences are widespread in nature and that the polymorphism in the CS protein of P. vivax is also present in the nonrepeat region. PMID- 1885564 TI - Sequence requirements for the editing of apolipoprotein B mRNA. AB - Apolipoprotein (apo) B48 is produced in the mammalian intestine by a tissue specific RNA-editing mechanism, which mediates a C to U conversion at position 6666 in apoB mRNA. This generates an inframe translation stop codon (UAA) in place of glutamine (CAA) at position 2153. To establish the sequences required for editing we have used an in vitro conversion assay to monitor the editing of synthetic RNAs by rat intestinal extracts. Transcripts containing 55 nucleotides (positions 6649-6703) or more of human apoB mRNA sequence were edited in vitro. Transcripts containing 42 nucleotides (positions 6648-6689) and 26 nucleotides (positions 6662-6687) were edited at 62 and 24% efficiency, respectively, of the 55-nucleotide sequence. To delineate the precise sequence requirements for editing, mutants were generated where 6-nucleotide sections of the 55-base region were changed to anti-sense sequence. Mutation of the 12-nucleotide region immediately downstream of C-6666 abolished editing, and mutation of 6-base sequences immediately 3' and 5' of this 12-nucleotide region significantly reduced editing. Having identified the key region of interest, a panel of 46 mutant RNAs carrying single base substitutions or deletions between nucleotide positions 6657 and 6685 was constructed. Mutagenesis in the sequence 5' TGATCAGTATA-3' (positions 6671-6681) downstream of C-6666 had the most dramatic effect, since almost all mutations abolished or greatly reduced conversion in vitro. These results suggest that editing is a highly sequence-specific process. We propose that this downstream region is a recognition and/or binding site for the editing enzyme. A search for this sequence in other genes may help to reveal other RNAs that undergo editing. PMID- 1885565 TI - Molecular cloning of cDNA for rat cathepsin C. Cathepsin C, a cysteine proteinase with an extremely long propeptide. AB - A cDNA for rat cathepsin C (dipeptidylaminopeptidase I) was isolated. The deduced amino acid sequence of cathepsin C comprises 462 amino acid residues: 28 NH2 terminal residues corresponding to the signal peptide, 201 residues corresponding to the propeptide, and 233 COOH-terminal residues corresponding to the mature enzyme region. Four potential glycosylation sites were found, three located in the propeptide region, and one in the mature enzyme region. The amino acid sequence of mature cathepsin C has 39.5% identity to that of cathepsin H, 35.1% to that of cathepsin L, 30.1% to that of cathepsin B, and 33.3% to that of papain. Cathepsin C, therefore, is a member of the papain family, although its propeptide region is much longer than those of other cysteine proteinases and shows no significant amino acid sequence similarity to any other cysteine proteinase. PMID- 1885566 TI - 6-Deoxy-D-talan and 6-deoxy-L-talan. Novel serotype-specific polysaccharide antigens from Actinobacillus actinomycetemcomitans. AB - Serotype-specific polysaccharide antigens from Actinobacillus actinomycetemcomitans ATCC 29523 (serotype a) and NCTC 9710 (serotype c) were extracted from whole cells by autoclaving and purified by ion-exchange chromatography and gel filtration. Analysis of component sugars by gas-liquid chromatography-mass spectrometry, high performance liquid chromatography, and NMR together with optical rotation data showed that the serotype a antigen was composed solely of 6-deoxy-D-talose, whereas the serotype c antigen consisted of 6-deoxy-L-talose. Structural analysis indicated that both of these antigens were composed of closely related repeating units, -3)-6-deoxy-alpha-D-Talp-(1-2)-6 deoxy-alpha-D-Talp-(1-(sero type a) and -3)-6-deoxy-alpha-L-Talp-(1-2)-6-deoxy alpha-L-Talp-(1-(sero type c). 1H and 13C NMR analysis showed that both of these serotype antigens contained one acetyl group/2 sugar residues. These acetyl groups localized at the O-2 position of 3-linked 6-deoxy-D-talose (serotype a) or O-4 position of 3-linked 6-deoxy-L-talose residues (serotype c), respectively. These results coupled with our previous findings on the serotype b antigen (Amano, K., Nishihara, T., Shibuya, N., Noguchi, T., and Koga, T. (1989) Infect. Immun. 57, 2942-2946) showed that the serotype antigens from A. actinomycetemcomitans are a group of novel polysaccharides with structural features closely related biosynthetically. PMID- 1885567 TI - Interaction of animal mitochondrial EF-Tu.EF-Ts with aminoacyl-tRNA, guanine nucleotides, and ribosomes. AB - The mammalian mitochondrial complex consisting of elongation factors EF-Tu and EF Ts (EF-Tu.Tsmt) is capable of efficiently binding aminoacyl-tRNA to the ribosome in the presence and absence of guanine nucleotides. In the presence of GTP the binding reaction is catalytic. In the absence of guanine nucleotides, or in the presence of a non-hydrolyzable GTP analog, only one round of ribosome binding occurs. EF-Tu.Tsmt is capable of forming a ternary complex with GTP and Escherichia coli Phe-tRNA as demonstrated by gel filtration chromatography, nitrocellulose filter binding, and by protection of the aminoacyl-tRNA bond from hydrolysis. GDP and the non-hydrolyzable GTP analog guanyl-5'-yl imidodiphosphate are also capable of facilitating ternary complex formation with EF-Tu.Tsmt, but are less effective. No kinetic advantage results from the formation of this ternary complex prior to ribosome binding, and EF-Tu.Tsmt may actually bind aminoacyl-tRNA directly to the ribosome prior to binding GTP. These results suggest that a variation of the prokaryotic elongation cycle is occurring in animal mitochondria. N-Ethylmaleimide inhibits the activity of EF-Tu.Tsmt in polymerization and in ribosome binding. However, the activity of the EF-Tsmt which can be measured independently, is not altered. PMID- 1885568 TI - Effects of pH and calcium ion on self-association properties of two dimeric phospholipases A2. AB - The monomer-dimer equilibria of the dimeric phospholipases A2 from Crotalus atrox and Agkistrodon piscivorus piscivorus venoms were examined chromatographically as a function of pH and in the presence versus absence of the essential cofactor, calcium ion. At neutral pH without calcium, the subunits of both enzymes reequilibrated sufficiently slowly that dimer and monomer were separated by size exclusion chromatography. At pH 4.2 and lower, the dimers underwent rapid dissociation and reassociation, eluting as single broad peaks whose position as a function of applied protein concentration could be analyzed to determine association constants using an algorithm that estimates these values based on elution positions. Lowering the pH from 7.0 to 4.2 increased the self-association constant of the C. atrox enzyme by 1 order of magnitude and that of the A. p. piscivorus dimer by a factor of 3. Calcium ion, an essential cofactor of phospholipase A2, converted the kinetic behavior of the dimers at neutral pH from slow to virtually instantaneous on the time scale of the chromatography runs, 40 min. Calcium ion also altered the thermodynamic stability of the enzymes; the association constant of A. p. piscivorus phospholipase A2 in neutral pH buffer was reduced by approximately 2 orders of magnitude, whereas that of C. atrox was increased by a factor of 6. The structural basis for the disparate effects of calcium ion on these two acidic, dimeric venom phospholipases A2 is uncertain. This study illustrates the importance of calcium ion and pH on the solution behavior of the dimeric members of this class of enzymes. PMID- 1885569 TI - Characterization of a recombinant single-chain molecule comprising the variable domains of a monoclonal antibody specific for human fibrin fragment D-dimer. AB - A recombinant single-chain molecule, scFv-K12G0, containing the variable domains of the monoclonal antibody MA-15C5, specific for fragment D-dimer of human cross linked fibrin, was constructed and expressed in Spodoptera frugiperda, Sf9, insect cells. The Arg108 carboxyl-terminal amino acid of the variable domain of the light-chain of the antibody was connected through a synthetic Ala-Gly-Gln-Gly Ser-Ser-Val peptide linker with the Gln1 amino-terminal amino acid of the variable domain of its heavy chain. scFv-K12G0 was secreted by the infected Sf9 cells at a rate of 10 micrograms/10(6) cells within 48 h, resulting in conditioned medium with a maximal concentration of 15 mg of scFv-K12G0/liter. The molecule, purified to homogeneity by ion exchange chromatography and gel filtration, migrated as a single Mr band on reduced sodium dodecyl sulfate-gel electrophoresis. It bound to immobilized fragment D-dimer with an affinity constant of 4.0 x 10(9) M-1 (2.0 x 10(10) M-1 for intact MA-15C5). Clearing of scFv-K12G0 from the circulation in rabbits occurred with an initial half-life (t1/2 alpha) of 10 min and a clearance of 5.1 ml min-1, as compared to 90 min and 210 ml min-1 for intact MA-15C5. Nephrectomy resulted in a prolongation of t1/2 alpha to 110 min, suggesting that the rapid clearance of scFv-K12G0 occurs primarily via the kidney, presumably by glomerular filtration. The results indicate that the single-chain recombinant molecule scFv-K12G0 is secreted in functionally intact form and suggest that it may be useful for targeting of radioisotopes or plasminogen activators to blood clots in vivo. PMID- 1885570 TI - Molecular dissection of translation initiation factor IF2. Evidence for two structural and functional domains. AB - By means of limited proteolysis of Bacillus stearothermophilus initiation factor IF2 and genetic manipulation of its structural gene, infB, we have been able to produce (or hyperproduce) and purify two polypeptide fragments corresponding to two structurally and functionally separate domains of the protein. The first is the G-domain (approximately 41 kDa), which makes up the central part of the molecule and contains the conserved structural elements found in all GTP/GDP binding sites of G-proteins. This domain is resistant to proteolysis in the presence of GTP or GDP, retains the capacity to interact with the 50 S subunit, binds weakly to the 30 S subunit, and displays ribosome-dependent GTPase activity with an approximately 2-fold higher Km for GTP and the same Vmax as compared with intact IF2. The second is the C-domain (approximately 24 kDa), which corresponds to the COOH-terminal part of IF2 and constitutes an extraordinarily compact domain containing the fMet-tRNA binding site of IF2. In spite of its negligible affinity for the ribosomes, the C-domain weakly stimulates the ribosomal binding of fMet-tRNA, presumably by affecting the conformation of the initiator tRNA molecule. PMID- 1885571 TI - Identification, purification, and characterization of major antigenic proteins of Campylobacter jejuni. AB - Evidence from developing countries and volunteer studies indicates that immunity to Campylobacter jejuni and Campylobacter coli may be acquired, but the antigenic basis for this protection is poorly defined. We have purified to homogeneity four proteins with molecular weights of 28,000 (PEB1), 29,000 (PEB2), 30,000 (PEB3), and 31,000 (PEB4) from epidemic C. jejuni strain 81-176 using acid extraction and sequential ion-exchange, hydrophobic interaction, and gel filtration chromatography. The relative amino acid compositions of these four proteins are similar. NH2-terminal sequence analysis indicates that all four proteins are different, although the first 35 amino acids of PEB2 and PEB3 are 51.4% homologous. Isoelectric focusing showed that all four are basic proteins with pI of 8.5 for PEB1 protein and greater than 9.3 for the others. Use of the purified proteins as antigens in an IgG enzyme-linked immunosorbent assay (ELISA) found that seroconversion to the PEB1 or PEB3 proteins occurred in 15 of 19 patients with sporadic C. jejuni or C. coli infection. In comparison, only two, six, and 14 of these patients seroconverted to PEB2, PEB4, or the acid extract antigen. In an ELISA with whole bacterial cells as antigens, antiserum to the acid-extracted antigens showed broad recognition of C. jejuni, C. coli, C. fetus, C. lari, and Helicobacter pylori. Antiserum to PEB1 recognized all 35 C. jejuni and all 15 C. coli strains but none of the isolates of the other three bacterial species. The PEB1 and PEB3 proteins appear to be candidate antigens for both a Campylobacter vaccine and for serological assays for the pathogen. PMID- 1885572 TI - Expression of a hybrid Cu/Zn-type superoxide dismutase which has high affinity for heparin-like proteoglycans on vascular endothelial cells. AB - Since plasma levels of enzymes, such as superoxide dismutase (SOD), that scavenge reactive oxygen species are low, surface membranes of endothelial and parenchymal cells of various tissues are often exposed to oxidative stress. To dismutase superoxide radicals efficiently in and around vascular endothelial cells, we constructed a fusion gene encoding a hybrid SOD (HB-SOD) consisting of human Cu/Zn-SOD and a C-terminal basic peptide that binds to heparin-like proteoglycans. The fusion gene was expressed in yeast, and the resulting HB-SOD was highly purified. Upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis, HB-SOD revealed a protein band with an apparent molecular weight of 20,000. HB-SOD bound to endothelial cells of aortic segments by a mechanism which was inhibited by heparin but not by antithrombin III. When injected intravenously to rats, 125I-labeled HB-SOD rapidly disappeared from the circulation; the rate of disappearance was decreased by heparin. Less than 1% of the injected HB-SOD was found in the urine 20 min after administration at which time more than 70% of SOD was excreted in its intact form. Immunohistochemical studies revealed that HB-SOD predominantly bound to heparin-like proteoglycans on endothelial cells of the artery and other tissues. HB-SOD might permit studies on pathophysiological roles of superoxide radicals in and around vascular endothelial cells in vivo. PMID- 1885573 TI - Novel cold-sensitive cytosolic 3,5,3'-triiodo-L-thyronine-binding proteins in human red blood cell. Isolation and characterization. AB - Four cytosolic 3,5,3'-triiodo-L-thyronine-binding proteins (CTBP) were isolated from hemoglobin-free human erythrocyte on DEAE-cellulose column by linear gradient of NaCl (0-0.4 M). CTBP I, II, and IV underwent rapid loss of their activities at low temperatures, whereas CTBP III was cold-insensitive. Reactivation of cold-inactivated CTBPs by warming was obtained at 20 and 37 degrees C. CTBP I, II, and IV were not inhibited by thiol-blocking agents, whereas CTBP III was blocked. Scatchard analysis of L-3,5,3'-triodo-thyronine binding showed a high affinity site with Kd on the order of 10(-10) M for CTBP II and Kd values of about 10(-9) M for CTBP I and IV and of about 10(-8) M for CTBP III. The order of affinity of iodothyronine analogues to CTBPs was similar in CTBP I, II, and IV but different in CTBP III. Chromatography on Sephacryl S-200 HR showed the elution of a single peak for each CTBP. The apparent molecular weights were about 200,000, 200,000, 25,000, and 60,000 for CTBP I, II, III, and IV, respectively. The physiological relevance of these CTBPs is discussed. PMID- 1885574 TI - Palmitoylation of cysteine 69 from the COOH-terminal of band 3 protein in the human erythrocyte membrane. Acylation occurs in the middle of the consensus sequence of F--I-IICLAVL found in band 3 protein and G2 protein of Rift Valley fever virus. AB - One of the major physiologic functions of erythrocytes is the mediation of chloride-bicarbonate exchange in the transport of carbon dioxide from the tissues to the lungs. The anion exchange is mediated by a typical polytopic transmembrane protein in the cell membrane, designated Band 3. A carboxyl-terminal peptide of Band 3 was affinity-labeled with pyridoxal phosphate, a substrate for the anion transport system, and then sequenced (Kawano, Y., Okubo, K., Tokunaga, F., Miyata, T., Iwanaga, S., and Hamasaki, N. (1988) J. Biol. Chem. 263, 8232-8238). The 10th amino acid residue of the peptide could not be determined, suggesting post-translational modification of the residue. In the present communication, we have investigated the molecular structure of human Band 3 and the COOH-terminal 8500-dalton peptide using gas-liquid chromatography-mass spectrometry. Band 3 was modified covalently by fatty acids and these acids were released from Band 3 by hydroxylamine treatment at either pH 7 or 11, indicating that the linkage between Band 3 and the fatty acid is a thio ester bond. 1 mol of Band 3 interacted with 1 mol of fatty acid at a cysteine residue located 69 residues from the COOH terminus of Band 3. The fatty acids used in the modification were myristate, palmitate, oleate, and stearate, with palmitate being the major component. The esterified site is close to the site affinity-labeled with pyridoxal phosphate (Kawano, Y., Okubo, K., Tokunaga, F., Miyata, T., Iwanaga, S., and Hamasaki, N. (1988) J. Biol. Chem. 263, 8232-8238). The amino acid sequence including the acylation site was Phe-Thr-Gly-Ile-Gln-Ile-Ile-Cys-Leu-Ala-Val-Leu, which is conserved in the G2 protein of Rift Valley fever virus as Phe-Ser-Ser-Ile-Ala-Ile Ile-Cys-Leu-Ala-Val-Leu. The G2 protein, like Band 3, is a polytopic transmembrane protein. Although acylation of the cysteine residue of G2 protein has not been examined, the Phe-X-X-Ile-X-Ile-Ile-Cys-Leu-Ala-Val-Leu sequence could be a common motif for fatty acylation of certain membrane proteins. PMID- 1885576 TI - Structural function of residue-209 in coumarin 7-hydroxylase (P450coh). Enzyme kinetic studies and site-directed mutagenesis. AB - Residue-209 plays a critical role in determining the substrate and product specificity of cytochrome P450coh. In order to investigate further the structural function of residue-209 in coumarin 7-hydroxylase reaction, we measured the enzyme-kinetic properties of wild-type P450coh and its mutants in which residue 209 was substituted with various amino acids. In general, the Km and Vmax values for coumarin increased as the size of residue-209 became smaller and Vmax values decreased. The size of residue-209, therefore, was a principle factor determining Km, Kd, and Vmax values of P450coh. Although the polarity and charge also increased the Km value consistently, they altered Vmax and Kd values in an irregular manner. The substitution of serine for residue-209 increased the Vmax, while the substitution of lysine decreased it. Coumarin 7-hydroxylase activity was inhibited weakly by indan, but competitively and strongly by 2-coumaranone. Moreover, Ki values for the inhibitor were similar to Km values of the corresponding, mutated P450s. The results indicate, therefore, that residue-209 is localized in a proposed substrate-binding sequence 1 which binds to the 2-keto group of coumarin and directs its 7-position toward the sixth ligand of heme. Consequently, the identity of residue-209 determines not only the binding of coumarin in P450coh, but also the other reaction step(s) of coumarin 7 hydroxylation. PMID- 1885575 TI - Phosphorylation regulates the activity of the eEF-2-specific Ca(2+)- and calmodulin-dependent protein kinase III. AB - The activity of the eukaryotic elongation factor 2 (eEF-2)-specific Ca(2+)- and calmodulin-dependent protein kinase III (CaM PK III) is regulated by phosphorylation. The kinase can be inactivated by treatment with alkaline phosphatase and subsequently reactivated by endogenous protein kinase. This kinase can be substituted for by the catalytic subunit of cAMP-dependent protein kinase but not by casein kinase II. The purified kinase preparation contains only one protein as judged by gel electrophoresis. This protein has a molecular mass of approximately 90 kDa and an isoelectric point of 5.2. Reactivation of the eEF 2 kinase is associated with the phosphorylation of this protein. The amino acid sequence obtained from the 90-kDa protein reveals substantial homology with that of murine heat shock protein 86 (HSP 86) a member of the HSP 90-family. Conventional preparations of HSP 90 contain an inactive eEF-2 kinase that could be activated after dephosphorylation and phosphorylation by the catalytic subunit of cAMP-dependent protein kinase. PMID- 1885577 TI - Functional cloning of a Dictyostelium discoideum cDNA encoding GMP synthetase. AB - A functional cloning procedure has been used to recover a cDNA coding for the GMP synthetase of Dictyostelium discoideum. The enzyme is encoded by a single gene, which is actively transcribed during growth, but not during development. The open reading frame encodes a protein of 718 amino acids with a predicted molecular mass of 79.6 kDa. The Dictyostelium enzyme has extensive homology with the GMP synthetase of Escherichia coli and regional homology to other glutamine amidotransferases. PMID- 1885578 TI - Vitamin A status regulates hepatic lecithin: retinol acyltransferase activity in rats. AB - The activity of lecithin:retinol acyltransferase (LRAT) was determined in microsomes from the liver and small intestine of rats with differing vitamin A status. In animals depleted of retinol, as judged by undetectable liver vitamin A stores and low plasma retinol concentrations, hepatic LRAT activity was almost undetectable, whether assayed with retinol bound to cellular retinol-binding protein or solvent-dispersed retinol. In contrast, neither the activity of intestinal LRAT nor that of acyl-CoA:retinol acyltransferase in either liver or intestine differed from that of vitamin A-adequate rats. During the course of vitamin A depletion, liver LRAT activity fell progressively, nearly in parallel to the decrease in plasma retinol concentration. Oral repletion of vitamin A depleted rats with 0.8 mg of retinol resulted in a very rapid restoration of plasma retinol concentration and full recovery of hepatic LRAT activity within 24 h, together with deposition of retinyl ester in the liver. These data strongly implicate LRAT activity in liver as responsible for the storage of hepatic retinyl esters. Retention of the intestine's capacity to esterify retinol during vitamin A deficiency provides a mechanism for capture of dietary vitamin A, while reduced hepatic LRAT activity may function to redirect retinol in liver from storage to other metabolic pathways. PMID- 1885580 TI - Mutational analysis of the ligand-binding domain of the prolactin receptor. AB - The recent isolation and sequencing of the rat liver prolactin (PRL) receptor cDNA (clone F3) revealed that the receptor is a small molecular weight protein (nonglycosylated form, Mr 33,000; glycosylated form, Mr 42,000) comprised of 291 amino acids. A second form of the PRL receptor exists (591 amino acids) that contains a much longer cytoplasmic domain. In the present study, site-directed point mutations of the 5 conserved cysteine (Cys) residues and of the three potential N-linked glycosylation sites in the extracellular domain of the rat PRL receptor were constructed to assess their involvement in hormone binding. In addition, a truncation mutant (T delta 237) lacking 55 of 57 intracellular amino acids was constructed to determine the influence of the cytoplasmic domain on ligand-receptor interactions. Binding studies of transiently transfected COS-7 cells demonstrated that serine substitution of the first 4 Cys residues (Cys12, Cys22, Cys51, and Cys62) completely eliminated binding of 125I-ovine PRL and 125I U5 and -U6, two monoclonal antibodies that bind the receptor molecule outside the PRL-binding domain. RNA blot analysis of the transfected cells showed that both the wild-type and mutant clones had similar levels of expression of receptor mRNA. Immunoblot analysis demonstrated that lack of PRL binding in these mutants was not due to incomplete processing of the protein, since the fully glycosylated Mr 42,000 form of the receptor was seen. Mutation of Cys184 had no effect on affinity or dimerization capacity of the receptor, suggesting the 5th cysteine is not directly involved in the binding domain. Carbohydrate groups of some receptors have been shown to be involved in ligand-receptor interactions as well as intracellular trafficking. This does not appear to be the case for the PRL receptor, since there was no corresponding decrease in affinity for PRL or cell surface receptor expression, following mutation of each of the 3 asparagine residues to aspartate. Interestingly, T delta 237 showed a 4-5-fold increase in affinity for PRL as well as a marked increase in the number of receptor sites. Whole cell binding assays also demonstrated that loss of the cytoplasmic domain lead to inefficient recycling of the receptor. These studies suggest that the first 4 conserved Cys residues are crucial for ligand binding.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1885579 TI - The protein sequence responsible for lipoprotein membrane localization in Escherichia coli exhibits remarkable specificity. AB - Structural information defining an N-terminal sequence required for the membrane sorting of bacterial lipoproteins has been previously garnered through the study of a hybrid outer membrane (OM) lipo-beta-lactamase (LL) (Ghrayeb and Inouye (1984) J. Biol. Chem. 259, 463-467). Introduction of an aspartate as the second residue of mature LL (D2 mutant) causes an inner membrane (IM) localization of this protein (Yamaguchi, K., Yu, F., and Inouye, M. (1988) Cell 53, 423-432). Introduction of as aspartate at the third residue of mature LL (D3) causes a weaker IM sorting signal and when present as the fourth residue (D4), normal OM sorting occurs. A positively charged residue at the second position (K2) has no effect on OM localization. Remarkably, glutamate substitution at either the second (E2) or third (E3) position does not interfere with OM sorting. Sorting of the mutant D2 LL can be partially suppressed by introduction of a positively charged histidine (D2H3) or lysine (D2K3) at residue 3 of the mature protein. These results indicate that both the negative charge of the aspartate residue and some structural feature not present in a glutamate residue are required for sorting to the IM. The suppression of IM localization of the D2H3 LL double mutant can be eliminated by growing Escherichia coli at pH 8.4 to reduce the histidine partial positive charge. This result supports the essentiality of a negative charge in IM localization and indicates that the committed step in lipoprotein sorting is made in a cellular compartment, the periplasm, at equilibrium with the external pH. PMID- 1885581 TI - Contacts between 5 S DNA and Xenopus TFIIIA identified using 5-azido-2' deoxyuridine-substituted DNA. AB - A highly photosensitive analogue of thymidine, 5-azidodeoxyuridine 5' triphosphate, has been incorporated into 61-base pair (bp) DNA fragments corresponding to the central region of Xenopus somatic-type 5 S RNA genes such that 5-azidodeoxyuridine replaces some or all T residues in either the coding or noncoding strand of the TFIIIA binding site. Photolysis of TFIIIA.DNA complexes formed with these probes results in efficient, sequence-specific cross-linking to the Zn-finger protein providing direct evidence that this class of proteins have contacts in the major groove of their target sequence. Of the 20 T residues present in the 61-bp probes, greater than 90% of the cross-linking occurs from two sites in the 5 S RNA gene corresponding to T residues at positions 84 and 88 in the noncoding and coding strands, respectively. Digestion by V8 protease of the complex formed with the noncoding strand probe releases peptides not bound to the DNA. Amino acid sequence analysis of the remaining, cross-linked peptides indicates the region including zinc-finger 2 plus the finger 2-3 linker is in contact with position 84. The linker region between fingers 5 and 6 is also in close proximity to the major groove somewhere upstream from position 84. PMID- 1885582 TI - Inhibition of leukotriene A4 hydrolase/aminopeptidase by captopril. AB - Captopril ((2S)-1-(3-mercapto-2-methyl-propionyl)-L-proline) inhibited the bifunctional, Zn(2+)-containing enzyme leukotriene A4 hydrolase/aminopeptidase reversibly and competitively with Ki = 6.0 microM for leukotriene B4 formation and Ki = 60 nM for L-lysine-p-nitroanilide hydrolysis at pH 8. Inhibition was independent of pH between pH 7 and 8, the optimum range for each catalytic activity. Half-maximal inhibition of leukotriene B4 formation by intact erythrocytes and neutrophils required 50 and 88 microM captopril, respectively. In neutrophils and platelets neither 5(S)-hydroxyeicosatetraenoic acid, 12(S) hydroxyeicosatetraenoic acid, nor leukotriene C4 formation were reduced, indicating selective inhibition of leukotriene A4 hydrolase/aminopeptidase, not 5 lipoxygenase, 12-lipoxygenase, or leukotriene C4 synthase. In whole blood, captopril inhibited leukotriene B4 formation with an accompanying redistribution of substrate toward formation of cysteinyl leukotrienes. The decrease in leukotriene B4 was more substantial than the corresponding increase in cysteinyl leukotrienes suggesting that nonenzymatic hydration predominates over transcellular metabolism of leukotriene A4 by platelets during selective inhibition of leukotriene A4 hydrolase. Enalapril dicarboxylic acid and Glu-Trp Pro-Arg-ProGln-Ile-Pro-Pro which inhibit angiotensin-converting enzyme: angiotensin I, bradykinin, and N-[3-(2-furyl)acryloyl]Phe-Gly-Gly which are substrates; and chloride ions which activate angiotensin-converting enzyme did not modulate leukotriene A4 hydrolase/aminopeptidase activity. The results indicate that: (i) the sulfhydryl group of captopril is an important determinant for inhibition of leukotriene A4 hydrolase/aminopeptidase, probably by binding to an active site Zn2+; (ii) aminopeptidase and leukotriene A4 hydrolase display differential susceptibility to inhibition; (iii) there is minimal functional similarity between angiotensin-converting enzyme (peptidyl dipeptidase) and leukotriene A4 hydrolase/aminopeptidase; (iv) captopril may be a useful prototype to identify more potent and selective leukotriene A4 hydrolase inhibitors. PMID- 1885583 TI - Inhibition of venom phospholipases A2 by manoalide and manoalogue. Stoichiometry of incorporation. AB - We have previously described the irreversible inhibition of cobra venom phospholipase A2 (PLA2) by the marine natural product manoalide (MLD) (Lombardo, D., and Dennis, E. A. (1985) J. Biol. Chem. 260, 7234-7240) and by its synthetic analog, manoalogue (MLG) (Reynolds L. J., Morgan, B. P., Hite, G. A., Mihelich, E. D., and Dennis, E. A. (1988) J. Am. Chem. Soc. 110, 5172-5177). We have now made a direct comparison of the action of these two inhibitors on PLA2 from cobra, bee, and rattlesnake venoms and have found that MLG behaves kinetically similarly to MLD in all cases with only minor differences. The time courses of inactivation differ significantly between the three enzymes, however, with the inactivation of bee and rattlesnake PLAs2, occurring much faster than does the inactivation of the cobra venom enzyme. The enzymes also differ in their sensitivity to the presence of Ca2+ during the inactivation. Of the three enzymes, the most Ca(2+)-sensitive is the rattlesnake enzyme, which shows a much faster rate of inactivation in the presence of Ca2+ than in the presence of EGTA. However, the same rate of inactivation was also observed when the inhibitor Ba2+ was substituted for Ca2+, indicating that catalytic activity is not required for inactivation of the enzyme. To probe the mechanism of inactivation and to determine the stoichiometry of incorporation, we have synthesized 3H-labeled MLG and have found that inactivation of cobra PLA2 is accompanied by an incorporation of 3.8 mol of [3H]MLG/mol of enzyme. The same amount of 3H incorporation was observed when p-bromophenacyl bromide-inactivated PLA2 was incubated with [3H]MLG, again indicating that catalytic activity is not required for the reaction of PLA2 with MLG. All together, these results suggest that MLD and MLG are not suicide inhibitors of PLA2. A portion of the incorporated radioactivity was acid-labile, and dialysis of the radiolabeled PLA2 under acidic conditions resulted in a loss of about one-third of the enzyme-associated radioactivity, leaving 2.4 mol of [3H]MLG/mol of PLA2. In previous studies, amino acid analysis, which also included acid treatment, indicated that MLG-modified cobra phospholipase A2 contained 2.8 mol of Lys less than the native enzyme. Thus, 1 mol of [3H]MLG is incorporated per mol of Lys lost. The implications of this 1:1 stoichiometry of MLG to Lys on the mechanism of reaction of these inhibitors is discussed. PMID- 1885584 TI - Proper insertion of a complex membrane protein in the absence of its amino terminal export signal. AB - The MalF protein spans the Escherichia coli cytoplasmic membrane eight times. Deletion of the first transmembrane stretch of MalF, which acts as an export signal, results in a truncated protein that still exhibits high levels of maltose transport activity. These and additional results indicate that the orientation of a membrane protein is not determined by the amino-terminal export signal, topological information is distributed throughout the MalF protein, and insertion of a protein into the cytoplasmic membrane can occur nonsequentially. PMID- 1885585 TI - Differential regulation of expression of the multiple ADP/ATP translocase genes in human cells. AB - The expression of the genes encoding the three isoforms of the human ADP/ATP translocase (T1, T2, and T3) has been investigated in cultured cell systems under different experimental conditions, using isoform-specific probes. In several human cell lines tested, i.e. HeLa, Hep3B, 143B, HL60, the T3 gene is expressed as a single 1300-nucleotide mRNA, whereas the T2 gene produces two species of mRNA, 1450 and 1600 nucleotides in size. These two species, which are present in HeLa cells in approximately equivalent amounts, were shown to derive from the use of two different polyadenylation signals. The gene for the muscle-specific isoform of ADP/ATP translocase, T1, was not found to be expressed in any of the cell lines investigated. The levels of T2 and T3 mRNAs in HeLa cells are differentially affected by the growth conditions. In fact, the T2 mRNA level remains relatively constant throughout the exponential and stationary phases, whereas the T3 mRNA level decreases progressively in the second half of the exponential phase and in the stationary phase down to less than 50%. This difference in quantitative behavior of the two mRNAs must reflect changes in their rates of synthesis, since their half-lives are very similar (t1/2 = 5-6 h), with no significant growth-related differences. Treatment of HL60 cells with 12-O tetradecanoylphorbol-13-acetate or retinoic acid, two agents which induce cessation of cell proliferation and cell differentiation, resulted in a marked decrease in both T2 and T3 mRNA levels. Exposure of HeLa cells to chloramphenicol produced a pronounced decrease in the levels of both T2 and T3 mRNAs after 48 to 72 h of treatment. Half-life time measurements strongly suggested that this decrease reflected a reduction in the rate of synthesis of the two transcripts. Treatment of HeLa cells with dinitrophenol also produced a dramatic decrease in the steady state levels of both T2 and T3 mRNA, which, however, in contrast to the just mentioned situation, could be accounted for by a decrease in their metabolic stability. Control experiments indicated that the chloramphenicol- and dinitrophenol-induced changes were not a nonspecific consequence of mitochondrial dysfunction. The observations reported here clearly demonstrate that the expression of the multiple ADP/ATP translocase genes in human cells is sensitive to the cell physiological conditions, responding to the varying cellular demands by changes in the rate of synthesis or stability of their mRNAs. PMID- 1885586 TI - The substrate specificity of bovine and feline lysosomal alpha-D-mannosidases in relation to alpha-mannosidosis. AB - Lysosomal alpha-mannosidases were partially purified from bovine and feline liver and employed to digest a large number of oligosaccharides with structures corresponding to the oligomannosyl parts of complex, hybrid, and high-mannose glycans. The incubation products were identified by high pressure liquid chromatography with reference compounds of defined structure and by acetolysis. For all classes of substrates, the lysosomal alpha-mannosidases displayed a high degree of in vitro specificity with regard to the hydrolysis of mannose residues. Thus, in each case, 1 or at most 2 residues were always preferentially cleaved so that the degradative process proceeded down a well defined pathway. A comparison of the relative efficiency with which lysosomal alpha-mannosidases catalyzed the hydrolysis of particular oligosaccharides and of the structures of the resulting intermediates with those of the compounds accumulated in alpha-mannosidosis allows conclusions to be drawn regarding the nature of the enzymatic defect. In bovine alpha-mannosidosis, the oligosaccharides are those expected for a partial deficiency of normal lysosomal alpha-mannosidase, so that they correspond to intermediates in the normal catabolic pathway. In feline alpha-mannosidosis, in which the alpha-mannosidase deficiency is more severe than in cattle, the accumulated oligosaccharides primarily represent intact oligomannosyl moieties of N-linked glycans rather than the products of residual alpha-mannosidase activity. PMID- 1885587 TI - Effect of chlorate on the sulfation of lipoprotein lipase and heparan sulfate proteoglycans. Sulfation of heparan sulfate proteoglycans affects lipoprotein lipase degradation. AB - In avian-cultured adipocytes 76% of the newly synthesized lipoprotein lipase is degraded before release into the medium (Cupp, M., Bensadoun, A., and Melford, K. (1987) J. Biol. Chem. 262, 6383-6388). The same group (Cisar, L. A., Hoogewerf, A. J., Cupp, M., Rapport, C. A., and Bensadoun, A. (1989) J. Biol. Chem. 264, 1767-1774) has proposed that the interaction of lipoprotein lipase with a class of cell surface heparan sulfate proteoglycans is necessary for degradation to occur. To test further this hypothesis, the binding capacity of the plasma membrane for the lipase was decreased by inhibiting the sulfation of glycosaminoglycans with sodium chlorate, an inhibitor of sulfate adenyltransferase. Chlorate decreased sulfate incorporation into trypsin releasable heparan sulfate proteoglycans to 20% of control levels. The amount of uronic acid in the trypsin-releasable heparan sulfate proteoglycans remained constant. Therefore, chlorate decreased sulfation density on heparan sulfate chains by approximately 5-fold. In the same fractions, chlorate increased the median heparan sulfate Mr measured on Sephacryl S-300. Chlorate decreased the maximum binding of 125I-lipoprotein lipase to adipocytes by 4-fold, but no significant effects on the affinity constants were observed. Chlorate increased lipoprotein lipase secretion in a dose-dependent relationship up to 30 mM. Utilizing a pulse-chase protocol, it was shown that lipase synthesis in control and chlorate-treated cells was not significantly different and that the increased secretion could be accounted for by a decreased lipoprotein lipase degradation rate. In control cells 77 +/- 11% of the synthesized enzyme was degraded whereas in chlorate-treated cells degradation was reduced to 42 +/- 9% of the synthesized amount. The present study shows that decreased sulfation of heparan sulfate proteoglycans decreases the maximum binding of the lipase for the adipocyte cell surface. Consistent with the model that binding of lipoprotein lipase to cell surface heparan sulfate is required for lipase degradation, degradation is reduced in chlorate-treated cultures. In this report it is also shown that chlorate inhibits lipoprotein lipase sulfation and that desulfation of the enzyme has no effect on its catalytic efficiency or on its binding to cultured adipocytes. PMID- 1885588 TI - Glucosidase I, a transmembrane endoplasmic reticular glycoprotein with a luminal catalytic domain. AB - We have analyzed the functional domain structure of rat mammary glucosidase I, an enzyme involved in N-linked glycoprotein processing, using biochemical and immunological approaches. The enzyme contains a high mannose type sugar chain that can be cleaved by endo-beta-N-acetyl-D-glucosaminidase H without significantly affecting the catalytic activity. Based on trypsin digestion pattern and the data on membrane topography, glucosidase I constitutes a single polypeptide chain of 85 kDa with two contiguous domains: a membrane-bound domain that anchors the protein to the endoplasmic reticulum and a luminal domain. A catalytically active 39-kDa domain could be released from membranes by limited proteolysis of saponin-permeabilized membranes with trypsin. This domain appeared to contain the active site of the enzyme and had the ability to bind to glucosidase I-specific affinity gel. Phase partitioning with Triton X-114 indicated the amphiphilic nature of the native enzyme, consistent with its location as an integral membrane protein, whereas the 39-kDa fragment partitioned in the aqueous phase, a characteristic of soluble polypeptide. These results indicate that glucosidase I is a transmembrane protein with a luminally oriented catalytic domain. Such an orientation of the catalytic domain may facilitate the sequential processing of asparagine-linked oligosaccharide, soon after its transfer en bloc by the oligosaccharyl transferase complex in the lumen of endoplasmic reticulum. PMID- 1885589 TI - Characterization of Chinese hamster ovary cells that are resistant to 3-beta-[2 (diethylamino)ethoxy]androst-5-en-17-one inhibition of low density lipoprotein derived cholesterol metabolism. AB - The pharmacological agent U18666A (3-beta-[2-(diethylamino)ethoxy]androst-5-en-17 one inhibits the intracellular transport of low density lipoprotein (LDL)-derived cholesterol in Chinese hamster ovary (CHO) cells. LDL-derived cholesterol accumulates in the lysosomes of U18666A-treated cells causing delayed LDL mediated regulation of cellular cholesterol metabolism and impaired movement of LDL-derived cholesterol to other cell membranes. As a result of impaired LDL derived cholesterol transport, LDL-dependent growth of CHO cells is also inhibited by U18666A. By selecting for cell growth in the presence of U18666A, we have identified a CHO cell line, designated U18R, that is resistant to U18666A inhibition of LDL-derived cholesterol trafficking. When compared to parental CHO cells, U18R cells are relatively resistant to U18666A inhibition of LDL-derived cholesterol transport as well as LDL-mediated regulation of cellular cholesterol metabolism. In cell fusion experiments, the U18666A resistance observed in U18R cells displays a dominant phenotype. Identification of the U18666A-resistant factor may provide important insights toward the understanding of intracellular LDL-derived cholesterol regulation and trafficking. PMID- 1885590 TI - Photosystem II particles from Chlamydomonas reinhardtii. Purification, molecular weight, small subunit composition, and protein phosphorylation. AB - PSII particles from Chlamydomonas reinhardtii were purified according to the protocol of Diner and Wollman (Diner, B.A., and Wollman, F.-A. (1980) Eur. J. Biochem. 110, 521-526) followed by ion-exchange chromatography. They contained the psbA, psbB, psbC, and psbD gene products in a 1/1/1/1 stoichiometry, cytochrome b559, and several small polypeptides, and exhibited electron transfer from donor Z to acceptor QA (40-50 chlorophylls/reducible QA). Upon ultracentrifugation and molecular sieving in the presence of either lauryl maltoside or octaethylene glycol dodecyl ether (C12E8), they behaved as monomers of 440-510 kDa, including the detergent. C12E8 preparations also contained a small proportion of a partially interconvertible dimeric form. Four small subunits were identified by N-terminal sequencing, namely a 6.1-kDa nuclear encoded subunit and three chloroplast-encoded subunits homologous to psbE, psbK, and psbM gene products. Cytochrome b559 subunit alpha (psbE) of C. reinhardtii, but not subunit beta (psbF), was recognized by an antiserum raised against higher plant cytochrome b559. The products of the psbF, psbI, and psbN genes remained undetected, presumably because of blocked N termini. At least four polypeptides presented both phosphorylated and unphosphorylated forms (psbC, psbD, and psbH gene products, as well as an unidentified 5-kDa subunit). PMID- 1885592 TI - Functional unit of 30 kDa for proximal tubule water channels as revealed by radiation inactivation. AB - The high water permeability of kidney proximal tubules is of paramount importance for isotonic reabsorption of 70% of the glomerular filtrate, and water channels have been postulated to account for the high water permeability. Target analysis following radiation inactivation was used to probe the molecular size of the water channel. Samples of brush border membranes from rat renal cortex were subjected to 3-MeV electron pulses from the Van de Graaff accelerator at a temperature of -130 degrees C. The inactivation of the renal brush border enzymes, alkaline phosphatase, and maltase was used for internal standardization of accumulated dose measurements in target analysis of the water channel. Osmotic water permeability was measured by following the change in scattered light intensity upon rapid mixing of vesicles with a hypertonic solution using stopped flow spectrophotometry. The vesicle shrinkage response was biphasic and the rate of the fast phase decreased dose dependently by irradiation corresponding to a target size of 30 +/- 3.5 kDa. The total change in scattered light intensity was unaltered, indicating that irradiation did not destroy the lipid barrier. Our results provide strong support for the hypothesis that the high osmotic water permeability of renal proximal tubules results from a water channel-specific protein with a functional unit of 30 kDa. PMID- 1885591 TI - Stabilization by a disulfide bond of the N-terminal domain of a mutant troponin C (TnC48/82). AB - The regulatory activity of troponin C is reversibly inhibited by a disulfide bridge between cysteine residues introduced by site-directed mutagenesis in positions 48 and 82 (TnC48/82) in the N-terminal domain of rabbit skeletal troponin C (sTnC; Grabarek, Z., Tan, R.-Y., Tao, T., and Gergely, J. (1990) Nature 345, 132-135). In the present work we have investigated the effects of the disulfide on structural properties of TnC48/82 monitored by CD spectroscopy and limited trypsinolysis. The CD spectra of the mutant protein in the oxidized form (oxTnC48/82) with and without Ca2+ are similar to the corresponding ones of the reduced and carboxamidomethylated form (CAMTnC48/82), indicating that the disulfide has essentially no effect on the overall secondary structure. The N terminal domain of oxTnC48/82 is resistant to thermal unfolding, but that of CAMTnC48/82 is only slightly more stable than the corresponding domain of sTnC. In the presence of Ca2+ oxTnC48/82 is more resistant to trypsinolysis than sTnC whereas the rate of tryptic digestion of CAMTnC48/82 is the same as that of sTnC, indicating that peptide bonds adjacent to lysine residues at position 84 and 88, the sites of tryptic attack, are protected by the disulfide. The disulfide cross linked N-terminal peptide of TnC48/82 does not bind TnI, unlike its reduced or carboxamidomethylated forms. Our data indicate that the disulfide between Cys48 and Cys82 stabilizes the structure of the N-terminal domain of TnC and blocks its ability to interact with TnI. The effects of the disulfide appear to be restricted to the N-terminal domain of TnC. PMID- 1885593 TI - Ubiquinone biosynthesis in Saccharomyces cerevisiae. Isolation and sequence of COQ3, the 3,4-dihydroxy-5-hexaprenylbenzoate methyltransferase gene. AB - Ubiquinone (or coenzyme Q) is a lipid component of the respiratory chain in the inner mitochondrial membrane, in which it functions in electron transport. Recent reports show that ubiquinone and ubiquinone biosynthetic enzymes are present in both mitochondrial and nonmitochondrial membranes of cells (Kalen, A., Appelkvist, E.-L., Chojnacki, T., and Dallner, G. (1990) J. Biol. Chem. 265, 1158 1164) although the functions that ubiquinone may play outside of the mitochondrion are not understood. To study coenzyme Q synthesis and function we cloned the 3,4-dihydroxy-5-hexaprenylbenzoate (DHHB) methyltransferase gene by functional complementation of a yeast coenzyme Q mutant strain, defective in the COQ3 gene (Tzagoloff, A., and Dieckmann, C. L. (1990) Microbiol. Rev. 54, 211 225). This gene restores both coenzyme Q synthesis in the mutant strain and the ability to grow on media containing glycerol, a nonfermentable substrate. A one step in situ gene replacement with the cloned DHHB methyltransferase DNA directs integration to the yeast COQ3 locus on chromosome XV of Saccharomyces cerevisiae, establishing that the COQ3 locus encodes the DHHB methyltransferase structural gene. The predicted amino acid sequence of the yeast DHHB methyltransferase contains a methyltransferase consensus sequence and shows a 40% identity with an open reading frame of Escherichia coli, the gyrA5' hypothetical protein. This open reading frame is adjacent to the gyrA gene and close to the mapped location of the ubiG gene at 48 min on the E. coli chromosome. These results suggest that the E. coli gyrA5' open reading frame encodes a methyltransferase and may correspond to the ubiG gene, which is required for ubiquinone biosynthesis. PMID- 1885594 TI - Inactivation of chicken mitochondrial phosphoenolpyruvate carboxykinase by o phthalaldehyde. AB - Chicken liver mitochondrial phosphoenolpyruvate carboxykinase is inactivated by o phthalaldehyde. The inactivation followed pseudo first-order kinetics, and the second-order rate constant for the inactivation process was 29 M-1 s-1 at pH 7.5 and 25 degrees C. The modified enzyme showed maximal fluorescence at 427 nm upon excitation at 337 nm, consistent with the formation of isoindole derivatives by the cross-linking of proximal cysteine and lysine residues. Activities in the physiologic reaction and in the oxaloacetate decarboxylase reaction were lost in parallel upon modification with o-phthalaldehyde. Plots of (percent of residual activity) versus (mol of isoindole incorporated/mol of enzyme) were biphasic, with the initial loss of enzymatic activity corresponding to the incorporation of one isoindole derivative/enzyme molecule. Complete inactivation of the enzyme was accompanied by the incorporation of 3 mol of isoindole/mol of enzyme. beta Sulfopyruvate, an isoelectronic analogue of oxaloacetate, completely protected the enzyme from reacting with o-phthalaldehyde. Other substrates provided protection from inactivation, in decreasing order of protection: oxaloacetate greater than phosphoenolpyruvate greater than MgGDP, MgGTP greater than oxalate. Cysteine 31 and lysine 39 have been identified as the rapidly reacting pair in isoindole formation and enzyme inactivation. Lysine 56 and cysteine 60 are also involved in isoindole formation in the completely inactivated enzyme. These reactive cysteine residues do not correspond to the reactive cysteine residue identified in previous iodoacetate labeling studies with the chicken mitochondrial enzyme (Makinen, A. L., and Nowak, T. (1989) J. Biol. Chem. 264, 12148-12157). Protection experiments suggest that the sites of o-phthalaldehyde modification become inaccessible when the oxaloacetate/phosphoenolpyruvate binding site is saturated, and sequence analyses indicate that cysteine 31 is located in the putative phosphoenolpyruvate binding site. PMID- 1885596 TI - Regulation of endothelial cell prostaglandin synthesis by glutathione. AB - Prostaglandin synthesis in in vitro systems is dependent on glutathione and peroxide concentrations. We tested the effects of glutathione depletion and H2O2 exposure on prostaglandin synthesis in cultured porcine aortic endothelial cells. Depletion of glutathione using buthionine sulfoximine (BSO), diethylmaleate, and 2,4-chlorodinitrobenzene increased prostaglandin synthetic capacity. Production of prostacyclin, but not prostaglandin E2, from exogenous arachidonic acid was significantly greater than in controls. Glutathione depletion also resulted in enhanced production of prostacyclin from exogenous prostaglandin H2. These responses were not due to direct effects of glutathione-depleting agents on prostaglandin synthetic enzymes. Exposure to H2O2 also altered prostaglandin synthetic capacity in endothelial cells. While 5 microM H2O2 stimulated prostaglandin production from exogenous arachidonate, 25 and 50 microM were found to be inhibitory. Prostaglandin synthetic capacity was greater in BSO-treated cells which were exposed to 5 and 10 microM H2O2 than in cells exposed to H2O2 alone. However, prostaglandin synthetic capacity was greatly reduced in BSO treated cells exposed to 50 microM H2O2. Thus, normal levels of cellular glutathione exert an inhibitory influence on prostaglandin synthesis. However, glutathione depletion increases the sensitivity of prostaglandin synthesis to inhibition by 50 microM H2O2. PMID- 1885595 TI - The human gene for 11 beta-hydroxysteroid dehydrogenase. Structure, tissue distribution, and chromosomal localization. AB - The Type I (mineralocorticoid) receptor has identical affinities in vitro for cortisol and aldosterone. It has been suggested that the selective role of aldosterone in regulating sodium homeostasis relies on the microsomal enzyme 11 beta-hydroxysteroid dehydrogenase (11-HSD). This enzyme converts cortisol to its inactive metabolite, cortisone, preventing cortisol from binding to the Type I receptor. We have isolated human cDNA clones encoding 11-HSD from a human testis cDNA library by hybridization with a previously isolated rat 11-HSD cDNA clone. The cDNA contains an open reading frame of 876 bases, which predicts a protein of 292 amino acids. The sequence is 77% identical at the amino acid level to rat 11 HSD cDNA. The mRNA is widely expressed, but the level of expression is highest in the liver. Hybridization of the human 11-HSD cDNA to a human-hamster hybrid cell panel localized the single corresponding HSD11 gene to chromosome 1. This gene was isolated from a chromosome 1 specific library using the cDNA as a probe. HSD11 consists of 6 exons and is at least 9 kilobases long. The data developed in this study should be applicable to the study of patients with hypertension due to apparent mineralocorticoid excess, a deficiency in 11-HSD activity. PMID- 1885597 TI - Studies on the mechanism of functional cooperativity between progesterone and estrogen receptors. AB - Steroid response elements (SREs) cooperate with many different cis-acting elements including NF-1 sites, CACCC boxes, and other SREs to induce target gene expression (Schule, R., Muller, M., Otsuka-Murakami, H., and Renkawitz, R. (1988) Nature 332, 87-90; Strahle, U., Schmid, W., and Schutz, G. (1988) EMBO J. 7, 3389 3395). Induction of gene expression can be additive or synergistic with respect to the level of activation by either transactivators. Two mechanisms have been proposed for how synergism occurs: 1) cooperative binding of transcriptional activators to DNA or 2) simultaneous interaction of individually bound activators with a common target protein. We have shown previously that cooperative binding of receptors is important for synergism between two progesterone response elements (PREs). Here we showed that an estrogen response element (ERE) and a PRE can also functionally cooperate and this synergism between an ERE and a PRE is not contributed by cooperative DNA binding. Furthermore, we have demonstrated that the activation domains of the progesterone receptor (PR) (C1Act) are required for synergism between two PREs and sufficient for confirming cooperative binding. However these two activation domains of PR are not sufficient for synergism between an ERE and a PRE. Additional regions within the NH2-terminal and COOH-terminal domains are also required for synergistic interaction between two heterologous SREs. PMID- 1885598 TI - Carbocyclic substrates for de novo purine biosynthesis. AB - The carbocyclic analogues of phosphoribosylamine, glycinamide ribonucleotide, and formylglycinamide ribonucleotide have been prepared as the racemates. Carbocyclic phosphoribosylamine was utilized as a substrate by the monofunctional glycinamide ribonucleotide synthetase from Escherichia coli as well as the glycinamide ribonucleotide synthetase activity of the eucaryotic trifunctional enzyme of de novo purine biosynthesis. Furthermore, carbocyclic glycinamide ribonucleotide was processed in the reverse reaction catalyzed by these enzymes. In addition, carbocyclic formylglycinamide ribonucleotide was converted, by E. coli formylglycinamide ribonucleotide synthetase, to carbocyclic formylglycinamidine ribonucleotide, which was accepted as a substrate by the aminoimidazole ribonucleotide synthetase activity of the trifunctional enzyme. This study has afforded carbocyclic substrate analogues, in particular for the chemically labile phosphoribosyl amine, for the initial steps of de novo purine biosynthesis. PMID- 1885599 TI - Role of protein kinase C in catecholamine secretion from digitonin-permeabilized bovine adrenal medullary cells. AB - The effects of staurosporine and K-252a, potent inhibitors of protein kinases, and 12-O-tetradecanoylphorbol-13-acetate (TPA) on catecholamine secretion and protein phosphorylation in digitonin-permeabilized bovine adrenal medullary cells were investigated. Staurosporine and K-252a (0.01-10 microM) did not cause large changes in catecholamine secretion evoked by Ca2+ in digitonin-permeabilized cells whereas these compounds strongly prevented TPA-induced enhancement of catecholamine secretion in a concentration-dependent manner. Incubation of digitonin-permeabilized cells with [gamma-32P]ATP resulted in 32Pi incorporation into a large number of proteins, detected as several major bands and darkened background in autoradiograms. Ca2+ and TPA increased phosphorylation of these proteins. Staurosporine and K-252a markedly inhibited Ca(2+)-induced and TPA induced increases in protein phosphorylation as well as basal (0 Ca2+) protein phosphorylation in digitonin-permeabilized cells. Long term treatment (24 h) of adrenal medullary cells with 1 microM TPA markedly decreased total cellular protein kinase C activity to about 5.3% of control. Pretreatment of the cells with 1 microM TPA strongly inhibited the TPA-induced enhancement of catecholamine secretion whereas it did not cause large changes in total cellular catecholamine amounts, Ca(2+)-induced catecholamine secretion, and cAMP-induced enhancement of catecholamine secretion from digitonin-permeabilized cells. From these results we conclude that protein kinase C plays a modulatory role in catecholamine secretion rather than being essential for initiating catecholamine secretion. PMID- 1885600 TI - Cell-specific and ubiquitous factors are responsible for the enhancer activity of the rat insulin II gene. AB - Pancreatic beta-cell-specific expression of the insulin gene is mediated, at least in part, by an enhancer element termed the rat insulin promoter element 3 (RIPES) found within the rat insulin II gene between positions -126 and -86. Here we identify three distinct factors interacting with RIPE3, namely 3a1, 3a2, and 3b1, which bind to the sequences between -100 to -90, -108 to -99, and -115 to 107, respectively. Factors 3a1 and 3b1 are beta-cell specific whereas 3a2 is ubiquitously distributed. The 3a1 site contains the consensus binding sequence (CANNTG) for a group of DNA-binding proteins called basic-helix-loop-helix proteins. We showed in this study that the 3a1 binding activity contains E12/E47, a member of the basic-helix-loop-helix protein family, or an E12/E47-like protein. Sequence comparison of the 3a2 and 3b1 binding sites suggest that they are unique and may bind to novel transcription factors. Mutation analysis of each individual binding site in transient expression experiments indicates that all of the three binding sites contribute to the enhancer activity of the RIPE3 in beta cells. Mutation in any one of the three binding sites not only disrupts binding of the corresponding factor but decreases RIPE3 enhancer activity by 4-7-fold. The results suggest that interactions among the 3a1, 3a2, and 3b1 factors are required for maximum enhancer activity of the RIPE3 in insulin-producing cells. PMID- 1885601 TI - 30-kDa heparin-binding protein of brain (amphoterin) involved in neurite outgrowth. Amino acid sequence and localization in the filopodia of the advancing plasma membrane. AB - A cDNA library constructed from mRNA of rat brain was used to clone the cDNA that encodes the 30-kDa heparin-binding protein (amphoterin) that is developmentally regulated in brain and enhances neurite outgrowth in cerebral neurons. cDNA and peptide sequencing identified a dipolar sequence that has been previously found in studies of high mobility group 1 protein: the 184-amino acid cationic region is followed by a cluster of 30 anionic residues. The mRNA encoding amphoterin is also developmentally regulated; it is strongly reduced in quantity after the rapid perinatal growth phase of the rat brain. Anti-synthetic peptide antibodies raised according to the sequence of amphoterin were shown to bind specifically to the protein isolated from brain, and were used to detect amphoterin in subcellular fractions and in immunostaining of cells. Amphoterin was found in the cytoplasm of the cell soma, in the cell processes, and the substrate-attached material. In cells that are at an active stage of spreading and extending their cytoplasmic processes amphoterin was especially associated with plasma membrane filopodia. The distinct localization to the filopodia of the advancing plasma membrane suggests that endogenous amphoterin has a role in the extension of neurite-type cytoplasmic processes in developing cells. This inference is further supported by the finding that both anti-amphoterin and the anti-synthetic peptide antibodies in the culture media strongly inhibit the outgrowth of cytoplasmic processes. PMID- 1885603 TI - Biochemical composition and organization of higher plant photosystem II light harvesting pigment-proteins. AB - The light-harvesting complex (LHC) of barley photosystem II (PS II) was fractionated by Deriphat-polyacrylamide gel electrophoresis into five different pigmented components: one subcomplex (LHC IIb) and four pigment-proteins (LHC IIa, -c, -d, and -e). No loss of chorophyll from the components occurred during fractionation, and violaxanthin is the only photosynthetic pigment that apparently occurs in thylakoids free of association with protein. Each LHC II component has a distinct stoichiometry of neoxanthin, violaxanthin, lutein, chlorophyll a, and chlorophyll b. LHC IIa, -d, and -e were obtained as monomeric pigment-proteins, each of which contained one apoprotein Mr 31,000, 21,000, and 13,000, respectively. LHC IIc was also isolated as a monomer but it contained two poly-peptides of Mr 29,000 and 26,500, whereas the trimeric LHC IIb subcomplex (Mr 72,000) contained three subunits of Mr 28,000, 27,000, and 25,000, but not in equal stoichiometry. How the LHC II subunits are organized in PS II was examined. We isolated PS II subcomplexes which contained four of the LHC II subunits and the core complex (CC II) in unit stoichiometry; the relative strengths of association of the LHC II subunits with CC II are: LHC IIa greater than LHC IIc greater than LHC IIb greater than LHC IId. The LHC II subunits were associated with the native dimeric and not with the derived monomeric form of CC II. In addition, a multimeric LHC II sub-complex composed of the LHC IIa, LHC IIb, and LHC IId pigment-proteins was isolated. We propose that this LHC II subcomplex, which contained the Mr 28,000 and 25,000 subunits but lacked the Mr 27,000 subunit of LHC IIb and CC II. An LHC IIb pigmented fraction of LHC IIb and CC II. An LHC IIb pigmented fraction of Mr 250,000 was isolated which contained only the Mr 28,000 and 27,000 subunits. The LHC IIb subunits in this complex were the most highly phosphorylated on a protein basis. These data together with analyses of the chlorophyll b-less barley chlorina f2 mutant were used to construct a model for the LHC II pigment-protein arrangement in higher plant PS II. PMID- 1885602 TI - CCAAT displacement protein as a repressor of the myelomonocytic-specific gp91 phox gene promoter. AB - The cytochrome b heavy chain (gp91-phox) is expressed exclusively in terminally differentiating myelomonocytic cells. The human gp91-phox gene spans approximately 30 kilobases, and is divided into 13 exons. A ubiquitous factor that is indistinguishable from the CCAAT-binding factor CP1 interacts in vitro with the distal gp91-phox promoter CCAAT box motif. CP1 binding is prevented, however, by a CCAAT displacement protein (CDP) that binds to the region surrounding the CCAAT box. CDP DNA-binding activity is found in nuclear extracts prepared from cells in which the endogenous gp91-phox gene is transcriptionally inactive, but is absent or reduced in expressing cells, consistent with CDP functioning as a repressor of gp91-phox transcription. Introduction of gp91-phox promoter/reporter constructs into nonexpressing cells yields significantly less expression than that produced by the parental reporter vector alone. The reduction in expression is relieved when the CDP/CP1-binding site is removed from the gp91-phox promoter, confirming that it is a target for repression. No derepression is observed if the CP1-binding site is selectively mutated. Derepression of expression exhibited upon deletion of the CDP/CP1-binding site suggests that, in addition to blocking the interaction of the CCAAT-binding factor with the gp91-phox promoter, CDP may also repress transcription mediated through a distinct cis-element(s). We propose that down-regulation of CDP DNA binding activity is a necessary step in the induction of myelomonocytic-specific expression of the gp91-phox gene. PMID- 1885604 TI - Molecular cloning, sequencing, and expression of human myocardial fatty acid ethyl ester synthase-III cDNA. AB - Fatty acid ethyl ester synthase-III (FAEES-III), previously purified to homogeneity from human heart, metabolizes ethanol nonoxidatively. Using a derived partial amino acid sequence and corresponding oligonucleotide probes, the cDNA for this enzyme has been cloned from a human heart lambda gtll library. Of the five positive clones obtained, one contained a complete coding region (630 base pairs) and the entire 3'-noncoding region (41 base pairs). From this nucleotide sequence the complete 210 amino acid sequence of FAEES-III (Mr 23,307) is reported. Comparison of its amino acid sequence with that of glutathione S transferase pi-1 suggests that they belong to the same gene family since they differ in only six nucleotides and four amino acids. The sequence of FAEES-III was also compared with those of placental glutathione S-transferase and the basic glutathione S-transferase. FAEES-III was 84% homologous with placental glutathione S-transferase but only less than 10% homologous with the basic glutathione S-transferase. Northern blots demonstrate expression of FAEES-III mRNA in normal human liver, placenta, and heart. In all cases, the mRNA for the enzyme is 0.7 kilobase in size. MCF-7 cells transfected with FAEES-III cDNA have a 14-fold increase in synthase activity and a 12-fold increase in glutathione S transferase (GST) activity compared with control cells. MCF-7 cells transfected with GST pi-1 cDNA have a 13-fold increase in GST activity compared with control cells but no increase in synthase activity. When the supernatant of COS-7 cells transfected with FAEES-III cDNA were immunoblotted with rabbit FAEES-III antibody, a band at 24 kilodaltons was demonstrated. Thus, we have obtained the first cDNA and amino acid sequence for a human FAEES-III which also has significant GST activity, and we have identified 4 residues potentially responsible for conferring ethanol recognition to GSTs. PMID- 1885605 TI - Characterization and molecular cloning of a putative binding protein for heparin binding growth factors. AB - A novel Mr 17,000 heparin-binding protein was purified from culture medium conditioned by A431 human epidermoid carcinoma cells. This protein, designated HBp17, was found to bind the heparin-binding peptide growth factors HBGF-1 and HBGF-2 in a noncovalent, reversible manner. In addition HBp17 was found to inhibit the biological activities of both HBGF-1 and HBGF-2. Both the binding and inactivation of HBGF-1 and HBGF-2 by HBp17 were abolished by heparin. Full-length 1163-base pair HBp17 cDNA was cloned and sequenced by using the polymerase chain reaction technique. The deduced primary structure of HBp17 consisted of 234 amino acids including each of five partial peptide sequences obtained from proteolytic fragments of purified HBp17. The encoded protein included a 33-residue N-terminal signal sequence for secretion and a single potential N-linked glycosylation site. No homology with any known protein was found for the deduced primary structure of HBp17. The expression of HBp17 mRNA was found to occur preferentially in normal human keratinocytes and in squamous cell carcinomas. This pattern of HBp17 gene expression suggests that this binding protein for HBGFs 1 and 2 has a physiological role in squamous epithelia. PMID- 1885607 TI - The periodically expressed TMP1 gene of Saccharomyces cerevisiae is subject to START-dependent and START-independent regulation. AB - The rate of transcription of the Saccharomyces cerevisiae gene encoding thymidylate synthase (TMP1) fluctuates periodically during the cell cycle. The simplest explanation for this pattern of expression is that transcription occurs during the late G1 and early S phases and does not occur during other stages of the cell cycle. In this report, however, we show that TMP1 is subject to regulation that results in at least three different levels of expression: essentially nondetectable expression during stationary phase (G0), moderate level expression in START-arrested growing cells (START-independent), and a high level of expression in proliferating cells (START-dependent). Our analysis also shows that upstream elements important for START-independent expression and required for START-dependent expression are located within a 37-base region. PMID- 1885606 TI - A DNA conformational alteration induced by a neighboring oligopurine tract on GAATTA enables nicking by EcoRI. AB - The pseudo EcoRI site GAATTA in the U3 region of the long terminal repeat of human immunodeficiency virus, which is flanked by a 26-base pair oligopurine tract, is readily nicked by either EcoRI or RsrI. The strand-specific nick occurs predominantly between the G and A residues and is independent of negative supercoiling. Other GAATTA sites surrounded by random (non-oligopurine) sequences are not nicked by these restriction endonucleases. However, other types and lengths of oligopurine tracts are effective in inducing the nicking in neighboring GAATTA sites. Hence, we propose that the flanking oligopurine tracts induce an altered DNA conformation on the GAATTA target site which may be similar to the transition state induced by EcoRI when binding to its canonical recognition site. Gel retardation analyses on restriction fragments containing the oligopurine-GAATTA-oligopurine sequences suggest the presence of helical axis distortions which are consistent with this interpretation. PMID- 1885608 TI - Unusual metabolism of the yeast actin amino terminus. AB - In this paper we have examined the post-translational modifications of the NH2 terminus of actin from the yeast Saccharomyces cerevisiae. Like actins examined previously, this actin contains an acetylated NH2 terminus. Actins in other organisms undergo a unique post-translational processing event in which the initial amino acid(s) are removed by an actin-specific processing enzyme in an acetylation-dependent reaction. This is defined as actin processing. In yeast, actin retains its initiator Met in vivo and is thus not processed even though a rat liver actin processing enzyme can process yeast actin in vitro. This lack of actin processing appears to be a general property of fungi, as the actin from three other species, Aspergillus nidulans, Schizosaccharomyces pombe, and Candida albicans are not NH2 terminally processed either. Yeast actin is a class I actin; its initiator Met directly precedes an acidic residue. We converted yeast actin to a class II species by inserting a Cys codon between the Met-1 and Asp-2 codons. In normal class II actins the Cys residue is removed as acetyl-Cys during processing. Neither the mutant actin nor chick beta-actin (a class I actin) are processed when expressed in yeast. S. cerevisiae thus appears to be also incapable of processing exogenous actins. Further study of the mutant actin containing a Cys at position 2 shows that 30-40% of this actin is stably unacetylated. This unacetylated actin does not have a shorter half-life than the acetylated form. From these studies we conclude that 1) NH2-terminal actin specific processing is not required for actin function in yeast and three other fungi, 2) yeast are apparently incapable of processing any type of actin precursor, and 3) the stability of a yeast pseudo-class II actin is not affected by the acetylation state of the NH2 terminus. PMID- 1885609 TI - Different levels of regulation accomplish the switch from type II to type I collagen gene expression in 5-bromo-2'-deoxyuridine-treated chondrocytes. AB - The shift of chick embryo chondrocytes to a fibroblastic phenotype by 5-bromo-2' deoxyuridine (BrdUrd) has been used to examine the molecular basis of the switch from type II to type I collagen gene expression. Transcription rates of each of these three collagen genes before and after this shift were measured in nuclear run-on transcription assays with double-stranded 3'-cDNA probes specific for each of these three mRNAs. Degradation rates of each of these RNAs were calculated from the rate of decrease in the concentration of each RNA after the inhibition of synthesis with actinomycin D. The shut-off of the expression of the type II collagen gene during this shift was shown to occur at the transcriptional level, since the transcription rate of this gene decreased dramatically. The decay rate of the type II mRNA (half-life of approximately 15 h) is not significantly faster in BrdUrd-treated cells. The alpha 1(I) gene is transcribed at similar rates in untreated and shifted chondrocytes, but the steady state level of alpha 1(I) RNA in chondrocytes is only 1.5% of that in shifted cells. Although the measured degradation rate of the total alpha 1(I) RNA from untreated chondrocyte cultures is approximately the same as in shifted cells (half-life of approximately 12 h), indirect evidence suggests that this alpha 1(I) RNA is derived from a low level of fibroblast contamination of these chondrocyte cultures. The alpha 1(I) RNA synthesized by untreated chondrocytes is assumed therefore to be broken down very rapidly in the nucleus. The alpha 2(I) gene is also transcribed in untreated chondrocytes at rates similar to shifted cells but, unlike alpha 1(I) RNA, its steady state level in untreated chondrocytes is approximately 30% of its level in shifted chondrocytes. The increased level of alpha 2(I) RNA in shifted cells may be regulated in part by an increase in stability of the alpha 2(I) mRNA, which has half-lives of 5.2 and 10.4 h, respectively, in untreated and shifted chondrocytes. The alpha 2(I) RNA in the untreated chondrocytes was found to have a different 5' end from that present in the BrdUrd-shifted chondrocytes or in chick embryo fibroblasts. The presence of this altered RNA in untreated chondrocytes explains the absence of synthesis of the fibroblastic alpha 2(I) collagen polypeptide chains in these chondrocytes, despite the presence of the alpha 2(I) RNA as measured with 3' probes. PMID- 1885610 TI - In vivo regulation of monomer-tetramer conversion of pyruvate kinase subtype M2 by glucose is mediated via fructose 1,6-bisphosphate. AB - The activity of pyruvate kinase, subtype M2 (PKM2), is known to be increased by fructose 1,6-bisphosphate (Fru-1,6-P2), one of the metabolites in the glycolytic pathway. Recently, we have shown that in vitro, Fru-1,6-P2 activated the association of monomer to form the tetrameric PKM2. To ascertain whether this mode of regulation also occurs in vivo, we prepared monomer-specific monoclonal antibody and quantified the monomer formation in situ in cultured cells by immunocytochemistry. The intracellular Fru-1,6-P2 was manipulated by the glucose concentration in the media. At the physiological concentration of glucose (4-6 mM), 30-35% of PK existed as a monomer. However, PKM2 was dissociated into monomer within minutes after cells were deprived of glucose. The maximal level of monomer was detected after 1 h at 37 degrees C. Monomer was rapidly (within minutes) converted to tetramer after addition of glucose. Furthermore, when cells cultured in 10 mM of glucose were treated with cytochalasin B, an inhibitor of the glucose transporter, a maximal level of monomer was detected within 20-30 min. Determination of Fru-1,6-P2 indicated that its intracellular concentration decreased concomitantly with the reduction in glucose concentration in the medium. These results indicate that monomer-tetramer inter-conversion is a major in vivo cellular regulatory mechanism in response to changes in the extracellular glucose concentration via Fru-1,6-P2. PMID- 1885611 TI - N-Acetylglutamic acid: an extracellular nod signal of Rhizobium trifolii ANU843 that induces root hair branching and nodule-like primordia in white clover roots. AB - An extracellular metabolite purified from Rhizobium trifolii ANU843 was established as N-acetylglutamic acid (GluNAc) by 1H NMR and Fourier transform IR spectroscopy, gas chromatography/mass spectrometry of its methylated product, and organic synthesis. TLC analyses indicated that extracellular accumulation of GluNAc by R. trifolii ANU843 grown in defined BIII culture medium was dependent on induction of its bacterial nodulation (nod) genes and the positive regulatory gene nodD on its symbiotic plasmid. 1H NMR analyses showed less GluNAc in fractionated culture supernatants of nodL and nodM mutant derivatives of R. trifolii ANU843. GluNAc induced three morphological responses on axenic roots of white clover seedlings: (i) root hair branching; (ii) tip swelling followed by resumed elongation of root hairs; and (iii) a slight increase in foci of cortical cell divisions, which developed into nodule-like primordia. These biological activities of extracellular GluNAc from R. trifolii ANU843 were confirmed with authentic standards of GluNAc. These results indicate that extracellular accumulation of N-acetylglutamic acid is linked to flavone-dependent metabolism involving nodD, nodL, and nodM in R. trifolii ANU843. This constitutes the first report on the structure of a nod-dependent extracellular signal from R. trifolii that can affect root hair and nodule development in white clover and whose biological activity on this host has been confirmed with authentic standards. PMID- 1885612 TI - Posttranslational modifications of fibromodulin. AB - Tyrosine sulfate residues were identified in fibromodulin produced by tracheal chondrocytes, by tendon and sclera fibroblasts in primary culture, as well as in Chinese hamster ovary cells transfected with a construct containing fibromodulin cDNA. The tyrosine sulfate residues were located in the N-terminal part of fibromodulin. Thus, Chinese hamster ovary cells expressing a deleted variant of fibromodulin lacking the N-terminal 52 amino acids following the predicted signal peptide did not contain any tyrosine sulfate residues. The substitution with keratan sulfate chains was not restricted to chondrocytes, but was also identified in fibromodulin synthesized by bovine tendon fibroblasts and sclera fibroblasts, as well as in fibromodulin isolated from tendon. Digestion of fibromodulin with N-glycosidase F reduced the apparent size of fibromodulin to that of the core protein, as predicted from sequence analysis (Oldberg, A., Antonsson, P., Lindblom, K., and Heinegard, D. (1989) EMBO J.8, 2601-2604). Thus fibromodulin from cartilage, tendon, and sclera contains N-glycosidically linked oligosaccharides, some of which are extended to keratan sulfate chains. PMID- 1885613 TI - Mouse type II collagen gene. Complete nucleotide sequence, exon structure, and alternative splicing. AB - Several overlapping clones covering the entire mouse type II collagen gene including 10 kilobases (kb) of 5'- and 15 kb of 3'-flanking sequences were isolated from a cosmid library. The overall gene structure was determined by restriction mapping and sequencing. The gene spans 28.9 kb from the start of transcription to the polyadenylation site and contains 54 exons. It codes for a major mRNA species of 4910 bases which translates into a polypeptide of 1419 amino acids. A less abundant RNA species of 5110 bases contains additional sequences corresponding to an alternatively spliced exon 2. Except for the amino terminal propeptide (N-propeptide) domain the exon-intron organization of the mouse pro alpha 1(II) collagen gene is remarkably similar to genes for other fibrillar collagen types. The overall identity of the coding sequences of the mouse and human type II collagen genes is 89% at the nucleotide level, but only 37 amino acid changes occur within the mature alpha 1(II) collagen chains between mouse and man. Intron sizes are also conserved between the mouse and human genes but not with the chick alpha 1(II) gene. The promoter of the mouse type II collagen gene is similar to those of the rat and human genes containing a TATA box and several G + C-rich elements but no CCAAT box. The 3'-untranslated sequence contains two regions of high homology between chick, mouse, bovine, and human genes preceding the major polyadenylation site. Additional size variation in the mRNA arises from the use of a minor polyadenylation signal. Information on conserved noncoding sequences will help in studies on the regulation of the pro alpha 1(II) collagen gene. Detailed knowledge of the gene is also necessary for site-directed mutagenesis and work with transgenic mice. PMID- 1885614 TI - Functional domains of proteoliaisin, the adhesive protein that orchestrates fertilization envelope assembly. AB - Ovoperoxidase, the enzyme that hardens the sea urchin fertilization envelope, is inserted into the assembling extracellular matrix through the action of an intermediary protein, proteoliaisin (PLN). The domain structure of PLN, a large, rod-shaped protein that binds to ovoperoxidase and the vitelline layer, was examined by limited proteolytic cleavage. Purified proteolytic fragments of PLN were tested for their ability to bind ovoperoxidase, inhibit the binding of 125I PLN to the vitelline layer, or act as substrates for the hardening reaction. Based on these results, the vitelline layer-binding domain can be placed near the amino terminus, followed by the binding site for ovoperoxidase; the distal two thirds of the protein contain sites for ovoperoxidase-catalyzed dityrosine formation. The pentapeptide GRGDS (but not RGD) inhibited PLN-vitelline layer binding half-maximally at 0.2 mM. Moreover, PLN promoted adhesion of bovine aortic endothelial cells to plastic dishes, a process inhibited by GRGDS. Thus PLN is a new member of the adhesive protein family, the function of which is to coordinate the morphogenesis of a specific, rapidly assembled extracellular matrix. PMID- 1885615 TI - Novel purification of the catalytic domain of Golgi alpha-mannosidase II. Characterization and comparison with the intact enzyme. AB - Rat liver alpha-mannosidase II, a hydrolase involved in the processing of asparagine-linked oligosaccharides, is an integral membrane glycoprotein facing the lumen of Golgi membranes. We have previously shown (Moremen, K. W., and Touster, O. (1986) J. Biol. Chem. 261, 10945-10951) that mild chymotrypsin digestion of permeabilized or solubilized Golgi membranes will result in the cleavage of the intact 124,000-dalton alpha-mannosidase II subunit, releasing a 110,000-dalton hydrophilic polypeptide which contains the catalytic site. Consistent with the removal of a membrane binding domain, the chymotrypsin generated 110,000-dalton peptide was found exclusively in the aqueous phase in Triton X-114 phase separation studies, whereas the intact enzyme was found in the detergent phase. Taking advantage of this conversion in phase partitioning behavior, a purification procedure was developed to isolate the 110,000-dalton proteolytic digestion product as a homogeneous polypeptide for further characterization and protein sequencing at a yield of greater than 65% from a rat liver Golgi-enriched membrane fraction. An improved purification procedure for the intact enzyme was also developed. The two forms of the enzyme were compared yielding the following results. (a) The catalytic activity of the intact and cleaved forms of alpha-mannosidase II were indistinguishable in Km, Vmax, inhibition by the alkaloid, swainsonine, and in their activity toward the natural substrate GlcNAc-Man5GlcNAc. (b) Both the intact and cleaved forms of the enzyme appear to be disulfide-linked dimers. (c) The two forms of the enzyme contain different NH2-terminal sequences suggesting that the cleaved NH2 terminus contains the membrane-spanning domain. (d) Additional peptide sequences were obtained from proteolytic fragments and cyanogen bromide digestion products in order to create a partial protein sequence map of the enzyme. These results are consistent with a model common among Golgi processing enzymes of a hydrophilic catalytic domain anchored to the lumenal face of Golgi membranes through an NH2 terminal hydrophobic membrane-anchoring domain. PMID- 1885616 TI - Biosynthetic regulation of monobutyrin, an adipocyte-secreted lipid with angiogenic activity. AB - 1-Butyrylglycerol (monobutyrin) is a novel angiogenic compound that is synthesized and secreted during the differentiation of 3T3-F442A preadipocytes into adipocytes. To study the regulation of monobutyrin biosynthesis we have developed an assay utilizing the lgycerol kinase enzyme from Cellulomonas to quantitate the levels of this compound in cell-conditioned medium. Analysis of several cultured cell types, including tumor cell lines, indicated that monobutyrin production is detectable only from adipocytes, reaching a steady state concentration of approximately 1.0 microM in conditioned medium. Monobutyrin synthesis was demonstrated in vitro using [14C]butyryl-CoA with total homogenate or particulate fractions from adipocytes. Similar fractions from non adipocyte cell lines failed to synthesize monobutyrin. This biosynthetic activity was shown to be distinct by substrate competition studies from the microsomal sn glycerol-3-phosphate acyltransferase, whose activity is known to increase during adipocyte differentiation. The production of monobutyrin was hormonally regulated, as the addition of epinephrine to adipocytes caused a 10-fold increase in the amount of monobutyrin secreted. These results indicate that monobutyrin synthesis is adipocyte specific, occurs through an apparently novel particulate enzyme system, and is regulated in a hormone-dependent manner. The implications of these results for adipose physiology and angiogenesis are discussed. PMID- 1885618 TI - Characterization of cDNA clones encoding a human fibroblast caldesmon isoform and analysis of caldesmon expression in normal and transformed cells. AB - Overlapping cDNA clones encoding a low M gamma human nonmuscle caldesmon isoform (HUM 1-CaD) span the entire coding region (538 amino acids) as well as 111 base pairs (bp) of 5'-noncoding and 1249 bp of 3'-noncoding region. Northern blot probes derived from either the coding or 3'-noncoding region hybridized to a 4.3 kilobase mRNA in nonmuscle cells and a 5.2-kilobase mRNA in stomach tissue. Primer extension results indicated that the 5'-noncoding region of the HUM 1-CaD mRNA is approximately 700 bp in length and also suggested that 1-CaD mRNAs with common 5'-noncoding regions are expressed in both liver and fibroblast cells. Comparisons of the human, rat, and chicken 1-CaD amino acids sequences demonstrated that although each isoform has unique characteristics, extensive regions of conservation exist. Amino acids 27-53 and 97-127 are 100% identical in these isoforms while amino acids 297-531 of HUM 1-CaD are 94 and 85% identical to the rat and chicken 1-CaDs, respectively. In addition, the levels of HUM 1-CaD mRNA and protein appeared to be decreased by 2-4 fold in the transformed derivatives of KD and WI38 cell lines as judged by Northern and Western blot analysis. The results suggest that the decrease of 1-CaD protein in these transformed cells is a direct result of decreased 1-CaD mRNA synthesis and/or increased mRNA turnover. PMID- 1885617 TI - Molecular cloning and gibberellin-induced expression of multiple cysteine proteinases of rice seeds (oryzains). AB - We screened a cDNA library of germinating rice seeds with a cDNA for aleurain (cysteine proteinase from barley) and obtained three distinct types of cDNA clones encoding three species of cysteine proteinases (oryzains alpha, beta, and gamma). The deduced amino acid sequences are distinct in part, but, on the whole, are similar to one another. The three sequences all contain the catalytic triad Cys25-His159-Asn175 (papain numbering). The three oryzains are similar to one another and also to other known cysteine proteinases such as papain and cathepsin H with respect to the sequences around the active site residues and the COOH terminal Trp-rich region. Amino acid sequence comparison revealed that oryzains alpha and beta are similar not only to each other (70% similarity) but also to actinidin and papain (about 50%), whereas oryzain gamma was rather similar to aleurain (85%) and cathepsin H (60%). Northern blot analysis revealed that the mRNAs for the three oryzains are expressed only in seeds, not in shoots or roots, and show different expression profiles during germination and when the seeds are treated with gibberellic acid. Oryzains alpha and gamma are expressed continuously during germination with a maximum expression 5 days from the start of germination, but are present in neither ripening nor ripened seeds. On the other hand, oryzain beta is expressed not only during germination, but also in ripened seeds before germination. It was noted that the expression of the three oryzain mRNAs is enhanced in different manners by gibberellic acid but is not enhanced by other plant hormones such as auxin. The induction of oryzain beta mRNA is transient, reaching a maximum in 4 h from the addition of giberellic acid and diminishing rapidly thereafter, while the induction of oryzain alpha and gamma mRNAs continues over 5 days. Thus, multiple systems involving cysteine proteinases must be differentially involved in the germination process, probably under hormonal control. PMID- 1885619 TI - Purification and characterization of an enhancer-binding protein of the fibroin gene. I. Complete purification of fibroin factor 1. AB - An enhancer-binding protein of the fibroin gene, fibroin factor 1 (FF1), has been purified to homogeneity from crude nuclear extracts of posterior silk gland cells where this gene is transcribed specifically. There is a multiplicity of FF1; the FF1 activity was eluted as at least three major fractions on column chromatographies. FF1 is able to form a stable complex with the enhancer DNA sequence in the presence of another proteinous factor named FF2, which lacks ability to bind DNA molecules by itself. One of FF1 forms, FF1a, was purified with a combination of classical purification techniques without using a sequence specific affinity column, and identified as a protein with molecular mass 125 kDa using sodium dodecyl sulfate-polyacrylamide gel electrophoresis. To obtain homogeneous protein of FF1a, purification of more than 26,000-fold from the starting nuclear extract was necessary. PMID- 1885620 TI - Purification and characterization of an enhancer-binding protein of the fibroin gene. II. Functional analyses of fibroin factor 1. AB - Fibroin factor 1 (FF1) when coupled with fibroin factor 2 (FF2) is an enhancer binding protein of the fibroin gene. FF1a, one type of FF1, has been purified to homogeneity from crude nuclear extracts of posterior silk gland cells and identified as a protein with molecular mass 125 kDa (Suzuki, T., Matsuno, K., Takiya, S., Ohno, K., Ueno, K., and Suzuki, Y. (1991) J. Biol. Chem. 266, 16935 16941). FF1 is able to recognize and bind a sequence of -205 to -185 in the enhancer I of the fibroin gene in the presence of FF2. The binding sequence of FF1 with FF2 contains two repeats of the derivative of consensus sequence which is recognized by homeobox-containing proteins. Though FF1 activity to construct the major band complex I is specific to posterior silk gland cells, use of a specific antibody raised against FF1a showed that FF1 protein is ubiquitous in Bombyx cells. These results suggest the possibility that FF1 molecules present as multiple proteins might be specifically modified and activated for the binding to enhancer DNA in posterior silk gland cells. Since the FF1a antibody also inhibited a transcriptional enhancement activity governed by the enhancer sequence, we conclude that FF1 is one of the transcriptional factors of the fibroin gene. The functions of FF1 on fibroin gene transcription are discussed. PMID- 1885621 TI - Hepsin, a cell membrane-associated protease. Characterization, tissue distribution, and gene localization. AB - Hepsin, a putative membrane-bound serine protease, was originally identified as a human liver cDNA clone (Leytus, S.P., Loeb, K.R., Hagen, F.S., Kurachi, K., and Davie, E.W. (1988) Biochemistry 27, 1067-1074). In the present study the human hepsin gene was localized to chromosome 19 at q11-13.2. The messenger RNA of hepsin is 1.85 kilobases in size and present in most tissues, with the highest level in liver. Hepsin is synthesized as a single polypeptide chain, and its mature form of 51 kDa was found in various mammalian cells including HepG2 cells and baby hamster kidney cells. It is present in the plasma-membrane in a molecular orientation of type II membrane-associated proteins, with its catalytic subunit (carboxyl-terminal half) at the cell surface, and its amino terminus facing the cytosol. Hepsin is found neither in cytosol nor in culture media. The results obtained suggest that hepsin has an important role(s) in cell growth and function. PMID- 1885622 TI - Functional expression of furin demonstrating its intracellular localization and endoprotease activity for processing of proalbumin and complement pro-C3. AB - We have cloned a rat cDNA encoding furin which is structurally related to yeast Kex2 protease. Products of 88 and 94 kDa were obtained by in vitro transcription/translation of the cDNA in the absence and presence of microsomes. When the cDNA was transfected into COS-1 cells, furin was expressed as a major glycosylated form of 94 kDa, accompanied by a minor proteolytic form of 86 kDa, and found to be localized in the Golgi complex. Proalbumin and complement pro-C3 are intracellularly processed into their mature forms by cleavage at the dibasic residues Arg-Arg, a common cleavage signal found in many pro-type precursors. In cells transfected with the cDNA of C3 or albumin alone, only about half of each proform expressed was processed by an endogenous activity of the cells. When furin was coexpressed, the proforms of both C3 and albumin were completely processed into their mature forms. In addition, co-expression of rat alpha 1 protease inhibitor mutant (Met352----Arg) resulted in inhibition of the endogenous and exogenous processing activities, as observed for the naturally occurring mutant Pittsburgh which has been identified as a specific inhibitor for the processing enzyme. Taken together, these results indicate that furin is an endoprotease localized to the Golgi complex and capable of processing proalbumin and pro-C3 into the mature forms. PMID- 1885623 TI - Parental education and child mortality in Burundi. AB - This paper examines the relationship between parental education and child mortality in Burundi using data collected in the 1987 Demographic and Health Survey. Proportional hazards models are estimated to examine this relationship, while holding constant other known child mortality determinants. Parental education proves to be a key factor in explaining differences in child mortality, the effect of maternal education being particularly strong compared to paternal education. PMID- 1885624 TI - Voluntary sterilisation among Canadian women. AB - Using data from the 1984 Canadian Fertility Survey, proportional hazards modelling was employed to determine factors associated with the likelihood of voluntary sterilisation among 5315 women of childbearing age, and the trends in timing and differences in the likelihood associated with different age cohorts. Multivariate analysis suggests that educational attainment, parity and duration since last birth at the time of sterilisation, religious commitment, province of residence and marital status at the time of sterilisation, are all important predictors. Education and parity attainment emerged as the best predictors of the timing of voluntary sterilisation in all age cohorts, but the contribution of other covariates varies between cohorts. PMID- 1885625 TI - Marital mobility within Shahrestan Nowshahr, northern Iran. AB - Birth localities of spouses from two generations are examined, to assess the extent to which the observed patterns of marital mobility link the spatially separated and kin-structured sub-populations within the 'shah-restan' of Nowshahr. The results indicate localised marriages and short range movements from the village of birth in both generations. Temporal increase in the range of movement indicates the breaking down of isolation, thus providing greater possibilities for admixture and genetic homogeneity. PMID- 1885626 TI - Abortion in South Australia, 1971-86: an update. AB - Official statistics on abortion in South Australia for the period 1971-86 are analysed in terms of incidence, age of patients and nuptiality, reasons for abortion, method of termination, period of gestation, previous abortions and concurrent sterilisation. Demographic implications are discussed and recommendations are made for more education and counselling, especially for younger and unmarried women for whom the incidence of abortion seems to be rising. PMID- 1885627 TI - Breast-feeding, birth interval and child mortality in Bangladesh. AB - The 1975-76 Bangladesh Fertility Survey data show little evidence that breast feeding is the intermediate factor through which birth intervals influence child survival in Bangladesh. Preceding birth interval, subsequent pregnancy and breast feeding duration each have an independent influence on early mortality risk. Within a specific interval the risk of dying decreases with increase in duration of breast-feeding, and also with an increase in the time between the index birth and the next pregnancy. The death of the immediately preceding child in infancy has a significant negative effect on the survival chance of the index child at ages 1-5 months. However, death of the preceding child appears to have a significantly positive effect on the survival chance of the index child between ages 9 months and 5 years; this may be related to competition between siblings. PMID- 1885628 TI - Proximate determinants of child mortality in Liberia. AB - The study looks at the effects of maternal sociodemographic characteristics and the quality of the environment on child survival through two intervening variables, breast-feeding and prenatal care. A linear structural equation modelling approach was used to examine infant and child survival based on a weighted sample of 5180 Liberian children aged 0-5 years. The findings confirm previous studies, but also reveal complex relationships of the role of education, maternal age and breast-feeding in enhancing child survival. PMID- 1885629 TI - Infant mortality in Bangladesh: a review of recent evidence. AB - Estimates of child mortality are mainly based on reports by mothers on the survival status of their children. Infant mortality estimates from such data do not seem to have declined in recent years. The Bangladesh Bureau of Statistics sample registration infant mortality estimates appear to be suspiciously low. PMID- 1885630 TI - Sex preferences for offspring among men in the western area of Sierra Leone. AB - This study reveals evidence of a significant sex preference among men. Programmes aimed at changing men's views on the importance of the sex of a child must be implemented in order to reduce the desired family size and eventual fertility. PMID- 1885631 TI - Birth spacing and infant mortality in Brazil. AB - The effects of birth spacing on neonatal and post-neonatal mortality in Brazil were found to be very consistent with models based on data from other South American countries. The model for neonatal mortality simplified to three significant variables, whereas the model for post-neonatal mortality included four significant interactions. PMID- 1885632 TI - Education, fertility and contraception among Hindus and Roman Catholics in Goa. AB - Differences in age at marriage, fertility and contraceptive use are related to religious background, individual educational level and community level education. In general, the effects of community education are weak compared to individual level of education, but differences exist between Hindus and Roman Catholics. PMID- 1885633 TI - Some factors in the choice of male or female sterilisation in Aberdeen. AB - In a random sample of 84 men and 167 women, medical considerations, an intransigent attitude of one partner or a fear of adverse effects, were related to the decision on which partner should seek sterilisation. Only 19% of couples felt that they had a real choice between male and female sterilisation. PMID- 1885634 TI - Darwin Lecture. Development of controlled trials in preventive and therapeutic medicine. PMID- 1885635 TI - Current thoughts on the assessment of protein metabolism in humans. AB - An understanding of protein metabolism is crucial in increasing knowledge about wound healing and functional recovery after burns. Recent advances in the clinical study of protein metabolism were addressed at a conference sponsored by the Shriners Burns Institute that took place March 7 to 8, 1990. New methods of clinical study of protein metabolism involving various isotopic labeling techniques were discussed. Conference participants concluded that advances in quantitation techniques and modeling approaches promise a better understanding of human protein metabolism, but also thought that current techniques still have limitations. PMID- 1885636 TI - Analysis of burns caused by long-term exposure to a heating pad. AB - The potential for creating a second-degree burn by extended exposure to an electric heating pad was evaluated in a simple model. Extrapolation of empirical results from experiments in thermal burns and in hyperthermia indicated that a heating pad at the low power setting can produce a burn within a threshold time of approximately 12 to 20 hours. PMID- 1885637 TI - Malignancy and chronic wounds: Marjolin's ulcer. AB - Malignancy in chronic wounds is not uncommon and has been reported as occurring in chronic scars of diverse causes. We report an unusual case of bilateral thermal injuries of the lower extremities that 40 years later presented as very large, painful, fungating wounds of both lower legs. After histologic confirmation of squamous cell carcinoma, eradication of the disease required amputations of both the lower extremities and reconstructive procedures. In addition, we discuss current theories regarding the mechanism of malignant degeneration in chronic wounds and evaluate treatment on the basis of information currently available in the literature. PMID- 1885638 TI - Reduced bacteria on transplantable allograft skin after preparation with chlorhexidine gluconate, povidone-iodine, and isopropanol. AB - A comparison was made of the residual microbiologic contamination on transplantable allograft skin for burn wound coverage taken from cadaver donors prepared by two different protocols. One group was prepared with povidone-iodine, detergent, and 70% isopropanol; the other was prepared with these agents and 4% chlorhexidine gluconate (CG). The skin from each of the donor bodies was removed from independently prepared body areas. Without CG, 13.7% of donor body areas were contaminated; with CG, only 5.6% were contaminated. The number of gram positive bacterial species isolated from skin after CG preparation was dramatically reduced. The gram-positive bacterial contamination rate dropped from 12.1% to 2.2% of donor body areas, a drop of 82%. With CG, 12 of the 15 contaminant species were eliminated; and we saw a general reduction in the total number of contaminated body areas, a specific and pronounced reduction in gram positive bacteria, and an increase from 86.3% to 94.4% in the amount of skin obtained from donor cadavers that tested negative for bacterial contamination. PMID- 1885640 TI - Early upper-extremity prosthetic fit in patients with burns. AB - Patients with upper-extremity amputations necessitated by burn injury have frequently faced delays in prosthetic fit. At the Regional Medical Center, Memphis, Tennessee, seven patients required amputations because of burns. These injuries were electrical in four cases, thermal and crush in one case, thermal in one case, and steam and crush in one case. Five patients had below-elbow amputations, one had a bilateral below-elbow amputation, and one had a bilateral above-elbow amputation. All patients were fitted with prostheses within 30 days of the last definitive surgery on the amputated extremity. All patients continued to wear a prosthesis and no patient exhibited skin breakdown. Patients returned to independence with self care within 2 weeks and to preamputation activities within an average of 2.5 months. PMID- 1885639 TI - Helicopter transport of the patient with acute burns. AB - Helicopter transportation of acutely injured or ill patients has become common practice at most major medical centers. However, its specific effectiveness in the transportation of acute-condition patients with burns has never been critically assessed. This study, for the period 1984 through 1988, evaluated the use of the helicopter for transportation of acute-condition patients with burns to a regional burn center for a rural area. It is concluded that helicopter transport within a 180-mile radius in a non-hospital-based system is not appreciably faster than is ambulance transport, and does not clinically benefit most burned patients. Consideration such as safety, cost, and working space are discussed. It is recommended that at least one of three criteria be met before helicopter transfer is considered for patients with burns: the surface area involved should be enough to require a formal fluid resuscitation, an inhalation injury should be present or suspected, or there should be a possible need for an escharotomy. PMID- 1885641 TI - Regional fasciocutaneous flaps for the burned axilla. AB - The conventional approach for secondary correction of unstable axillary scars or contractures with skin grafting commonly risks failure of adherence and early recurrence of the problem, even in highly motivated patients. Potential early mobilization and the avoidance of postoperative splinting may be advantages of reconstruction with vascularized tissues instead. The local fasciocutaneous flap is advocated as a simple, rapidly elevated, single-staged option that preserves function while correcting these deformities. Although the dorsal thoracic fascial flaps are the most versatile in the axillary region, if they are unavailable or unsuitable, other unspecified but equally robust alternatives from the upper arm or anterolateral chest are similarly efficacious. PMID- 1885642 TI - A survey of pediatric discharge educational programs in North American burn units. AB - In this study we contacted all of the 149 major North American burn facilities that treat children. The survey determined topics covered in discharge teaching, personnel administering the programs, methods used, and obstacles encountered. The subjects addressed and the personnel involved have changed little from a decade ago. Unfortunately, one fourth of the centers still do not deal with emotional aspects of burns in their discharge programs. For program delivery, videotape is becoming an increasingly accepted teaching method. Eighty-five percent of burn facilities experienced barriers to patient education at discharge, with more than half reporting three or more difficulties. The most common difficulty was time constraints (50%), followed by language and sociocultural barriers (41%), lack of receptivity by clientele (39%), lack of educational materials and planning (26%), and inadequate funding (25%). Some of these problems might be alleviated by the establishment of a clearinghouse for burn educational materials. PMID- 1885643 TI - Computer analysis of the performance of the BTE Work Simulator. AB - The BTE Work Simulator (Baltimore, Therapeutic Equipment Co., Hanover, Md.) recreates the work environment by providing a rotatable shaft to which a variety of tools can be attached. The patient can simulate the coordinated muscle and joint movements involved in the work situation, exercising either isometrically or isotonically, and thereby increase the potential for return to work. The BTE Work Simulator has four major components: the exercise head to provide variable resistance, tools that attach to the exercise head, a control console containing a microprocessor that calculates work and power, and the Quest software package (Baltimore Therapeutic Equipment Co.). Quest provides four static/isometric and seven dynamic/isotonic tests that can be used to document the extent of a patient's impairment. In addition, it has daily treatment options and acts as an extensive data base capable of retrieving any stored test or treatment results. This software system greatly facilitates the use of the BTE Work Simulator by providing instant calculations of power and coefficients of variation, immediate patient feedback, graphic expansion of the data, and printed evaluation reports. PMID- 1885644 TI - Pressure therapy for the control of hypertrophic scar formation after burn injury. A history and review. AB - Devastating functional problems can result from the formation of hypertrophic scar tissue after burn injury. Although a patient with burns may have several medical problems to contend with because of the injury, most ongoing rehabilitation difficulties are a consequence of the continual wound contraction that occurs in immature burn scars. Treatment of hypertrophic burn scar consists of several surgical options and of pressure therapy, which traditionally involves wearing garments made from elasticized fabric. This article reviews the treatment of hypertrophic scar tissue, with emphasis on its history and on nonsurgical methods of managing the burn scar. PMID- 1885645 TI - A technique for control of hypertrophic scarring in the central region of the face. AB - Various methods are available for applying pressure to the central portion of the face to reduce hypertrophic scarring after burn injury. Our center uses an elastomer insert with a thermoplastic backing, which is formed over a plaster mold of the patient's face. The insert is worn under a traditional anti-burn scar face mask. We reviewed the records of 26 patients with hypertrophic scarring to the central portion of the face to assess the effectiveness of the insert. Seventeen (65%) of these patients wore the insert until scar maturation. Three of these 17 patients later required reconstructive surgery of the central face. Our findings suggest that pressure to this part of the face may be effective in decreasing hypertrophic scar formation. The insert described in this article is inexpensive and relatively easy to fabricate. PMID- 1885646 TI - Analysis of materials for splinting of the thermally injured patient. AB - Good results have been achieved in the treatment of patients with burns with new splinting materials and proper splinting techniques. This article focuses on the thermoplastic splinting materials Clinic and Spectrum (Northcoast Medical Inc., San Jose, Calif.) and the comparable thermoplastic products Polyform (Smith & Nephew Rolyan, Inc., Menomonee Falls, Wis.) and Orthoplast (Johnson & Johnson Orthopedics, New Brunswick, N.J.). Qualities such as self-bonding, recyclability, and rigidity were tested for these materials. Splint rigidity was measured by a calibrated hook scale and determined by the force per pound needed to bend the material 20 degrees. Spectrum and Clinic products were judged more economical and, we contend, they are therefore better choices for splinting the thermally injured patient. PMID- 1885649 TI - Motor proteins. PMID- 1885648 TI - Population requirements for statistical analysis of efficacy of burn prevention programs. PMID- 1885647 TI - Research priorities for burn nursing. Report of the Wound Care and Infection Control Group. AB - This study was designed to identify research priorities in burn nursing. The Delphi technique of sequential questionnaires was used for data collection. Ninety-four participants completed four rounds of questionnaires. One hundred one research questions were identified and prioritized according to impact on the welfare of patients with burns and impact on the profession of burn nursing. Twenty-three of these research questions concerned issues of wound care or infection control. This group of questions was further analyzed to determine priority research issues. The five most highly ranked questions in the category of wound care/infection control with regard to impact on patient welfare concerned healing of donor sites and skin grafts, wound cleansing, and the effect of pressure garments on wound healing. Similarly, the five most highly ranked questions with regard to impact on the profession of burn nursing concerned the impact of combining patients with burns and patients without burns in the same unit, healing of donor sites and skin grafts, care of the patient with burns who also has acquired immune deficiency syndrome, infection control, and dressing of the burn wound. PMID- 1885650 TI - Differential regulation of vertebrate myosins I and II. AB - Cell motility events require movement of the cytoskeleton. Actin-based movement is catalyzed by the mechanoenzyme myosin, which translocates toward the barbed end of actin filaments in an ATP-dependent fashion. There are two subclasses of myosin with different structures and functions: conventional filamentous myosin (myosin II) and monomeric myosin I. Vertebrate non-muscle myosins I and II function as similar actin motors in vitro, catalyzing virtually identical actin activated MgATP hydrolysis and motility. The functional diversification of these two enzymes results from their differential regulation. Calcium and tropomyosin, which activate the MgATP hydrolysis and motility of vertebrate non-skeletal muscle myosin II proteins, inhibit vertebrate (brush border) myosin I. The activities and regulation of brush border myosin I provide insight into conserved and unique features of the myosin mechanoenzymes and suggest how the functions of myosins I and II are divided in vertebrate cells. Brush border myosin I as an enzyme also contributes to our understanding of the molecular mechanism of motility. PMID- 1885652 TI - Studies using a fluorescent analogue of kinesin. AB - The microtubule motor protein kinesin has been conjugated with 5-iodoacetamido fluorescein (5-IAF). The analogue, AF-kinesin, supports organelle motility and the movement of microtubules. PMID- 1885651 TI - An approach to reconstituting motility of single myosin molecules. AB - Over the last five years, the value of in vitro motility assays as probes of the mechanical properties of the actin-myosin interaction has been amply demonstrated. Motility assays in which single fluorescent actin filaments are observed moving over surfaces coated with myosin or its soluble fragments are now used in many laboratories. They have been applied to a wide range of problems including the study of structure-function relationships in the myosin molecule and measurement of fundamental properties of the myosin head. However, one limitation of these assays has been uncertainty over the number of myosin heads interacting with each sliding filament, that frustrates attempts to determine properties of individual heads. In order to address this limitation, we have modified the conditions of the actin sliding filament assay to reduce the number of heads interacting with each filament. Our goal is to establish an assay in which the motor function of a single myosin head can be characterized from the movement of a single actin filament. PMID- 1885653 TI - MAPs and motors in insect ovaries. AB - MAPs and microtubule motor proteins from the massive microtubule translocation complexes within the ovaries of hemipteran insects have been identified and characterized. Both classes of proteins have been compared with those of other systems, and the function of both in the insect ovaries is speculated upon. PMID- 1885654 TI - Self-assembly pathway of nonsarcomeric myosin II. AB - Cells need to control the location and timing of actomyosin-dependent force generation, and appear to do so in the first instance by regulating myosin filament self-assembly (Yumura and Fukui, 1985). The mechanism of the self assembly is little understood. In vitro it is a true self-assembly, which requires a short domain at the C terminus of the myosin molecule. The availability of this domain appears suppressed by the folding of the molecule into a compact, looped state. In vitro, the rate at which these looped molecules unfold turns out to be a key determinant of filament number and filament length. PMID- 1885655 TI - Small angle X-ray scattering studies on myosin. AB - Small angle X-ray scattering (SAXS) is a potentially powerful method for obtaining structural information from biological molecules in solution. The use of this technique in the laboratory has hitherto been limited by the long exposures necessary to obtain patterns on photographic film. Multi-wire area detectors, due to their high efficiency and absence of noise, enable patterns to be collected much more rapidly, typically in 1-2 h for a typical protein using laboratory sources. This opens up the possibility of using the technique on a semi-routine basis for a wide variety of problems. We outline the use of SAXS to characterise a large conformational change of myosin. PMID- 1885656 TI - The influence of pressure on actin and myosin interactions in solution and in single muscle fibres. AB - Studies of the molecular mechanism of motile activity require the capacity to examine the properties of individual, isolated molecular components and the properties of these same molecular components in the organised system. Pressure perturbation is one method which can be applied to motile systems at different levels of organisation. We show here that pressure perturbs a specific interaction between actin and myosin in solution and also perturbs the cycling crossbridge in a contracting muscle. PMID- 1885658 TI - Antibodies against vertebrate microfilament proteins in the analysis of cellular motility and adhesion. AB - Microinjection of specific antibodies can be an alternative and a supplement to genetic engineering in dissecting the function of individual cytoskeletal components. In this report, we describe some of the requirements for using this technique, its potential application in conjunction with morphological and biochemical analyses, and its limitations. Examples are given for the injection of antibodies to alpha-actinin, vinculin and myosin, and the effects of such treatment on adhesion, motility and cytokinesis of the recipient cells. PMID- 1885657 TI - Molecular cloning of protozoan myosin I heavy chain genes. AB - Myosins I are ubiquitous, nonfilamentous, actin-based mechanoenzymes originally discovered in protozoa. The extensive in vitro biochemical studies of purified protozoan myosins I are now being complemented with in vivo studies using cloned myosin I heavy chain genes and gene targeting techniques. Here we review briefly the systems and methods being used in these efforts to dissect protozoan myosin I structure and function using molecular genetic approaches. PMID- 1885659 TI - Phosphorylation of vertebrate smooth muscle and nonmuscle myosin heavy chains in vitro and in intact cells. AB - In this article we summarize our recent experiments studying the phosphorylation of vertebrate myosin heavy chains by protein kinase C and casein kinase II. Protein kinase C phosphorylates vertebrate non-muscle myosin heavy chains both in vitro and in intact cells. A single serine residue near the end of the helical portion of the myosin rod is the only site phosphorylated in a variety of vertebrate nonmuscle myosin heavy chains. There does not appear to be a site for protein kinase C phosphorylation in vertebrate smooth muscle myosin heavy chains. Casein kinase II phosphorylates a single serine residue located near the carboxyl terminus of the 204 x 10(3) Mr smooth muscle myosin heavy chain in vitro as well as in cultured smooth muscle cells. It does not phosphorylate the 200 x 10(3) Mr smooth muscle myosin heavy chain. However, the site is present in vertebrate nonmuscle myosin heavy chains. The 204 x 10(3) Mr myosin heavy chain of embryonic chicken gizzard smooth muscle is exceptional in not containing a site for casein kinase II phosphorylation. PMID- 1885660 TI - Recombinant DNA approaches to study the role of the regulatory light chains (RLC) using scallop myosin as a test system. AB - The ability to exchange reversibly the regulatory light chains (RLCs) from scallop myosin has provided us with a test system to probe the mechanisms of regulation mediated by the RLCs from vertebrate skeletal, vertebrate smooth and molluscan myosins. The cloning and expression of these RLCs, together with domain swapping and site-directed mutagenesis approaches, has allowed us to explore further the mechanisms involved and identify the functional importance of specific regions of the RLC molecule; for example, the presence of a high affinity metal binding site in the N-terminal domain and its interaction with the intact C-terminal domains are required for regulation. PMID- 1885661 TI - Manipulation and expression of molecular motors in Dictyostelium discoideum. AB - The eukaryote Dictyostelium discoideum is an attractive model organism for the study of cytoskeletal proteins and cell motility. The appearance and behavior of this cell closely resembles that of mammalian cells, but unlike mammalian cells, Dictyostelium offers the opportunity specifically to alter the cell physiology by molecular genetic approaches. PMID- 1885662 TI - The use of native thick filaments in in vitro motility assays. AB - Native thick filaments from the clam, Mercinaria mercinaria translocate actin filaments both toward and away from the center of the thick filament in an in vitro motility assay. The thick filaments from the adductor muscle are about 10 microns long whereas those from the catch muscle are 30-50 microns long. These thick filaments should prove useful in understanding the mechanism of myosin dependent movement of actin filaments. PMID- 1885663 TI - Molecular basis of myosin assembly: coiled-coil interactions and the role of charge periodicities. AB - Complementation of alternating zones of positive and negative charge in the myosin rod enables molecules to interact in a number of ways. This accounts for the complexity of the molecular organisation of thick filaments. However, directed mutagenesis of expressed LMM cDNA indicated that charge zone complementation is not a major driving force in myosin polymerisation. Instead, it probably serves to prevent unfavourable interaction geometries. PMID- 1885664 TI - Nuclear envelope dynamics and nucleocytoplasmic transport. AB - We have combined structural, biochemical and recombinant DNA methods to explore molecular interactions involved in nuclear envelope assembly dynamics and nucleocytoplasmic transport. Electron microscopy has established the overall architecture of the envelope and the relationship between nuclear pores, lamina fibres and pore-connecting fibrils. The lamin proteins that constitute the lamina resemble intermediate filament proteins, and assemble and disassemble during mitosis in response to phosphorylation. Lamins have been expressed in E. coli to facilitate structural investigations and the exploration of interaction sites with other envelope components. Disruption of envelopes has shown that nuclear pores are constructed from a central cylinder with cytoplasmic and nucleoplasmic rings. Examination of envelopes transporting gold-labelled nucleoplasmin has indicated that the transport pathway is complex and probably involves ring components in addition to the central cylinder. Molecular motors may be involved in changes in pore shape to enable transport and in the translocation mechanism. PMID- 1885665 TI - Bidirectional movement of actin filaments along tracks of heavy meromyosin and native thick filaments. AB - Flexibility of the myosin molecule was studied by an in vitro motility assay in terms of the direction of actin movement. Actin filaments can move in both directions on tracks of heavy meromyosin made on a nitrocellulose surface, and, furthermore, along the native thick filaments passing over their central bare zone. These observations indicate that the myosin molecule has a considerable flexibility in interacting with actin filaments. PMID- 1885666 TI - Regulation of the interaction between smooth muscle myosin and actin. AB - Phosphorylation of the regulatory light chain of smooth muscle myosin efficiently regulates the actin-activated ATPase activity of myosin filaments in solution and actin movement in an in vitro motility assay, independently of thin-filament regulatory proteins. Filaments containing both phosphorylated and dephosphorylated heads move actin at intermediate rates, depending on the relative proportions of the two myosin species. The decrease in velocity can be accounted for by mechanical interactions between phosphorylated heads and 'weak binding' dephosphorylated crossbridges. These results imply that shortening velocity could be modulated in any muscle by varying the relative proportions of two populations of crossbridges with different cycling rates. PMID- 1885667 TI - Implications of DNA replication for eukaryotic gene expression. AB - DNA replication has a key role in many developmental processes. Recent progress in understanding events at the replication fork suggests mechanisms for both establishing and maintaining programs of eukaryotic gene activity. In this review, I discuss the consequences of replication fork passage for preexisting chromatin structures and describe how the mechanism of nucleosome assembly at the replication fork may facilitate the formation of either transcriptionally active or repressed chromatin. PMID- 1885668 TI - Cellular invasion into matrix beads: localization of beta 1 integrins and fibronectin to the invadopodia. AB - We have examined the contribution of adhesion mechanisms to cell invasiveness by growing chicken embryo fibroblasts (CEF) or Rous sarcoma virus-transformed cells (RSVCEF) on fibronectin-coated crosslinked gelatin beads (FN-beads). RSVCEF attached more readily and spread more rapidly on FN-beads than CEF, suggesting an increase in the adhesion-related motility of the transformed cells. In addition, RSVCEF invaded the FN-beads, but CEF did not, by extending specialized cell surface protrusions called invadopodia at sites of cell invasion. FN removal by RSVCEF cultured on prelabeled fluorescent FN-beads (FL-FN) was evident at sites of invadopodia, and internalized FL-FN occurred in vacuoles near the ventral membrane of cells at sites of FN removal. The precise distribution of FN and integrins in cells invading FN-beads was determined by immunofluorescence and immunoelectron microscopy of frozen thin-sections. In both CEF and RSVCEF, beta 1 integrins and FN occupied separate intracellular compartments during the early stage of spreading on FN-beads. Later, beta 1 integrins were largely localized at the ventral cell surface of both CEF and RSVCEF. Polyclonal anti-integrin antibody recognizing beta 1 and several alpha chains, however, labeled both ventral and dorsal cell surfaces. During invasion by RSVCEF, beta 1 integrins were concentrated at extended invadopodia and also colocalized with internalized FL-FN material in phagocytic vesicles. Furthermore, secreted FN was deposited by RSVCEF at the base of invadopodia colocalizing with beta 1 integrin. Both FL-FN matrix removal and formation of the invadopodia were found to be resistant to treatment with GRGDS at concentrations that inhibit the interaction between cells and FN-beads. Thus, the localization of beta 1 integrins to the plasma membrane contacting immobilized FN results in an extremely tight cellular adherence to the matrix bead, that stabilizes invadopodia and also mediates endocytic clearance of degraded FN-matrix material. PMID- 1885669 TI - Spatial and temporal distribution of DNA replication sites localized by immunofluorescence and confocal microscopy in mouse fibroblasts. AB - The temporal course of replication monitored by 2- or 5-min pulses of bromodeoxyuridine (BrdUrd) incorporation in synchronized 3T3 cells was mapped by high-resolution light microscopy employing a charge-coupled device (CCD) camera and a confocal laser scanning microscope (CLSM). The cells were labeled simultaneously with monoclonal antibodies directed against BrdUrd and nuclear lamin, and stained with the A+T-specific dye 4',6-diamidino-2-phenylindole (DAPI). Stereoscopic reconstructions of cells showing both the lamin and BrdUrd distributions demonstrate that DNA replication occurs at discrete sites in the nucleus, the locations of which progress through a programmed sequence during S phase. Replication begins in a small number of sites in the interior of the nucleus exclusive of the nuclear membrane and proceeds rapidly in early S phase to encompass a relatively large number of small, discrete sites located throughout the nucleus, with the exception of the condensed heterochromatic regions. Replication is primarily confined to the condensed heterochromatic regions in mid-to-late S phase, and to the nuclear periphery at the end of S phase. These distinctive patterns demonstrate a programmed control of replication sites in the spatial domain in differentiated cell nuclei. PMID- 1885670 TI - Nuclear distribution of centromeres during the cell cycle of human diploid fibroblasts. AB - The distribution of centromeres in the interphase nuclei of human diploid fibroblasts was analyzed using anti-centromere immunofluorescence and laser scanning confocal microscopoy. The positions of the centromeres were placed within the nuclear chromatin distribution and presented some aspects of the dynamics of nuclear structure during the cell cycle. During the G1 phase of the cell cycle many of the centromeres were located in association with nucleoli or fused in chromocenters. A few centromeres were dispersed singly in the euchromatin. During S phase, the fused centromeres dispersed, often forming distinct patterns of rings or lines. At prophase, the centromere immunofluorescence condensed into distinct double dots upon the formation of the prophase chromosomes. Quantitative analysis by both image and flow cytometry showed that the intensity of immunofluorescence started to duplicate in mid S phase, well before the appearance of the double dots. The coalesence of the centromeres during G1 indicated that regions of the chromosome domains remain compacted and possibly sequestered from transcriptional activity. During S phase the chromatin and the coalesced centromeres dispersed for DNA replication. The dynamics of the centromeres and chromatin during the cell cycle seen here are evidence for a higher-order organization of nuclear structure that accompanies DNA transcription and replication. PMID- 1885671 TI - Genetic analysis of the relationships between the amoebal extranuclear spindle organizing centre and the plasmodial intranuclear spindle-organizing centre of Physarum during conjugation. AB - Physarum amoebae possess an extranuclear spindle-organizing centre (abbreviated SPOC), located in a typical centrosome with a pair of associated centrioles while plasmodia possess an intranuclear SPOC without centrioles. In order to ascertain whether, during conjugation, the plasmodial SPOC is derived from the amoebal one or is not related to it, we have constructed amoebal strains possessing two and three SPOCs and we have used as a genetic marker the frequency of polycentric metaphases in order to evaluate the number of SPOCs in the plasmodia. The results of both symmetrical crosses, i.e. between amoebae possessing the same number of SPOCs, and asymmetrical crosses, i.e. between amoebae possessing a different number of SPOCs, show that: (1) the number of SPOCs in plasmodia is dependent upon the number of SPOCs in either one of the two parental amoeba; (2) in no cross does the number of plasmodial SPOCs equal the sum of the parental amoebal SPOCs, but it corresponds to that of only one parent without any polarity of transmission in asymmetrical crosses. These results are consistent with the following model: (1) plasmodial SPOCs are derived from the amoebal ones; and (2) one set of parental SPOCs is lost, destroyed or inactivated in the zygote. PMID- 1885672 TI - Expression of lymphocyte perforin in the mouse uterus during pregnancy. AB - In situ hybridization and immunofluorescence were used to study the expression of a lymphocyte pore-forming protein (perforin) in the uterus of pregnant mice. Cells expressing perforin mRNA were detected as early as gestation day 5, whereas perforin protein was detected one or two days later. Although the number of cells expressing both perforin mRNA and perforin protein varied subsequently with time, they were consistently observed from the day of implantation until parturition. The highest levels of mRNA expression were observed sometime during midgestation. The high abundance of this cytolytic protein in the metrial gland during pregnancy and the time course of its expression thus suggest that GMG perforin expression is tightly regulated, probably hormonally, by the uterus, and that GMG cell perforin plays an important role in the normal completion of pregnancy. PMID- 1885673 TI - Dynamic regulation of yeast glycolytic oscillations by mitochondrial functions. AB - The control exerted in vivo by mitochondrial functions on the dynamics of glycolysis was investigated in starved yeast cells that were metabolizing glucose semianaerobically. Glycolytic oscillations were triggered after a pulse of glucose by inhibition of mitochondrial respiration with KCN, myxothiazol and antimycin A or in mutants in the bc1 complex (ubiquinol:cytochrome c reductase) that were largely deficient in respiratory capacity. Inhibition of the adenine nucleotide translocator by preincubation with bongkrekic acid also triggered a train of damped sinusoidal oscillations after glucose addition. The oscillations consisted of cycles of reduction and oxidation of the intracellular pool of nicotinamide nucleotides with periods of 45 s to 1 min and amplitudes of 0.8 mM or lower. Preincubation with the uncoupler carbonyl cyamide p (trifluoromethoxy)phenylhydrazone (FCCP) annihilated cyanide-induced oscillations of NAD(P)H. Evidence for de-energization of mitochondrial membranes in vivo was obtained by mitochondrial staining with dimethylaminostyryl-methyl pyridiniumiodine (DASPMI) of starved cells. The low rates of NADH reoxidation shown by respiratory mutants and the FCCP-treated X2180 strain open up the possibility that mitochondrial dehydrogenases also control glycolytic oscillations. Low rates of cytosolic NADH reoxidation induced by pyrazole, an inhibitor of alcohol dehydrogenase, were also associated with the disappearance of glycolytic oscillations. From experimental evidence and model calculations we conclude that the modulation of the levels of cytosolic ATP by mitochondrial functions in turn modulates the approach of the dynamic behavior of glycolysis to an oscillatory domain. The mitochondrial NADH dehydrogenase and the glycolytic steps associated with NADH reoxidation downstream from pyruvate appear to provide another control level of glycolysis dynamics in vivo. PMID- 1885674 TI - Expression in Escherichia coli of human lamins A and C: influence of head and tail domains on assembly properties and paracrystal formation. AB - We have expressed in Escherichia coli cDNA corresponding to human lamins A and C, together with a number of fragments produced using site-specific mutagenesis. The proteins produced in this way were characterised both biochemically and ultrastructurally, and appeared to retain their native conformation. Crosslinking showed that all fragments formed 4-chain molecular dimers ('tetramers') analogous to those formed by intact intermediate filament proteins. Shadowed preparations showed the presence of rod-like particles that closely resembled those observed for other intermediate filament proteins and their proteolytically prepared rod domains. Moreover, the expressed lamins and a series of fragments in which different domains had been deleted formed paracrystals similar to those observed with native material. Deletion of either the N- or C-terminal non-helical domains altered the solubility and aggregation properties of the expressed protein, indicating that both domains have a role in lamin assembly. PMID- 1885675 TI - Hair follicle stem cells? A distinct germinative epidermal cell population is activated in vitro by the presence of hair dermal papilla cells. AB - Germinative epidermal cells in the lower end bulb region of anagen hair follicles are highly active, and give rise to hair fibres through rapid proliferation and complex differentiation. They have often been termed hair follicle stem cells, but owing to difficulties in isolation and identification their properties have previously only been clearly documented in vivo. We aimed to isolate and culture germinative cells in vitro, and used microdissection methods to dissect a small but identifiable group of cells from complete follicles. Transmission electron microscopy confirmed that the isolated cells were identical to germinative epidermal cells in situ. SDS-PAGE was used to show that they did not have the same protein composition as epidermis from their immediate proximity (overlying hair matrix), or from other follicular (outer root sheath) and interfollicular (skin basal) regions. Moreover, the germinative cells were found to display morphology and in vitro behaviour that distinguished them from comparative epidermal cells. When cultured in media and on substrata normally conducive to epidermal cell growth they remained in a quiescent state, and did not divide or differentiate. In contrast to other epidermal cells that formed typical pavement like arrangements, germinative cells remained uniformly small, round and closely packed. However, when cultured in association with hair follicle dermal papilla cells they were radically stimulated into proliferative and aggregative behaviour. Furthermore, they were able to form organotypic-like structures, and exceptionally for skin-derived cell recombinations, a distinct basal lamina at the papilla-germinative cell junction. These results provide evidence that hair follicle germinative cells have intriguing properties that distinguish them from other follicular epidermis. The finding that they can be activated by dermal papilla cells reflects the intimate nature of the papilla-germinative cell relationship in situ, and should facilitate research into hair growth control mechanisms. The nature of germinative cells is discussed in the wider context of hair follicle stem-cell terminology. PMID- 1885676 TI - Cell density affects spreading and clustering, but not attachment, of human keratinocytes in serum-free medium. AB - Attachment, spreading and clustering of second-passage human human keratinocytes in serum-free medium have been evaluated within 24 h after plating, as a function of the density of the inoculum and of time, in two different strains. The results show that attachment is unaffected by cell density and differs significantly from strain to strain. Cell density affects the distribution of attached keratinocytes among three morphologically distinct classes: unspread, spread and clustered cells. The percentage of unspread keratinocytes shows a linear decrease at increasing cell density, and that of spread keratinocytes an increase, resulting from statistically significant increases in the percentages of both single and clustered cells. Spreading on uncoated surfaces appears therefore as an inducible phenomenon. The use of media conditioned by keratinocytes, fibroblasts and HeLa cells shows that keratinocytes specifically secrete a diffusible 'spreading factor'. We term this phenomenon 'autocrine induced spreading'. Preliminary physicochemical characterization suggests that a protein could be responsible for the spreading activity of conditioned media. The 'spreading factor' seems to act directly on the cells, and not through a modification of the plastic surface of the dishes, since most (greater than 70%) of the spreading activity can be recovered in the conditioned media used in pre-coating experiments. The percentages of clusters follow 'saturation' kinetics at increasing cell density, while the percentage of clustered cells increases linearly with the density of inoculum. Time-course experiments show that the rate of spreading is cell density and strain-independent. The percentages of clusters and of total clustered cells are time-independent, suggesting that cluster formation takes place in suspension.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1885677 TI - Cytodifferentiation of mouse mammary epithelial cells cultured on a reconstituted basement membrane reveals striking similarities to development in vivo. AB - In the present study we provide evidence that the cytodifferentiation of primary mouse mammary epithelial cells within the alveolar-like structures formed after culture on a reconstituted basement membrane resembles development in vivo during late pregnancy and early lactation. During the first two days in culture on a basement membrane gel in the presence of lactogenic hormones, epithelial cells isolated from mid-pregnant mice are disorganized and central lumina are largely absent. Levels of mRNA for the milk proteins, beta-casein and transferrin, are dramatically reduced. By the second or third day in culture, cytoplasmic polarization becomes evident and prominent apical junctional complexes are formed. Synthesis of both mRNA and milk protein is reinitiated at this time. By day 4, well-defined lumina appear, and abundant synthesis and secretion of casein and lipid is observed. A striking feature of this differentiation in culture is the specific localization of milk protein gene expression (beta-casein mRNA) to luminal epithelial cells in the alveolar-like structures. At the ultrastructural level, increased milk protein synthesis and secretion are paralleled by a fourfold increase in rough ER that resembles the dramatic increase in the ER observed in vivo following parturition. One indication of tissue-specific differentiation observed in later cultures (days 4-11) is the synthesis and secretion of abundant casein micelles. A second characteristic of lactating mammary epithelial cells in vivo that has not previously been observed in culture is the secretion of milk fat globules. Taken together, these observations indicate that mammary epithelial cells plated onto a reconstituted basement membrane differentiate to the lactating phenotype in culture. PMID- 1885678 TI - Migration of individual microvessel endothelial cells: stochastic model and parameter measurement. AB - Analysis of cell motility effects in physiological processes can be facilitated by a mathematical model capable of simulating individual cell movement paths. A quantitative description of motility of individual cells would be useful, for example, in the study of the formation of new blood vessel networks in angiogenesis by microvessel endothelial cell (MEC) migration. In this paper we propose a stochastic mathematical model for the random motility and chemotaxis of single cells, and evaluate migration paths of MEC in terms of this model. In our model, cell velocity under random motility conditions is described as a persistent random walk using the Ornstein-Uhlenbeck (O-U) process. Two parameters quantify this process: the magnitude of random movement accelerations, alpha, and a decay rate constant for movement velocity, beta. Two other quantities often used in measurements of individual cell random motility properties--cell speed, S, and persistence time in velocity, Pv--can be defined in terms of the fundamental stochastic parameters alpha and beta by: S =square root (alpha/beta) and Pv = 1/beta. We account for chemotactic cell movement in chemoattractant gradients by adding a directional bias term to the O-U process. The magnitude of the directional bias is characterized by the chemotactic responsiveness, kappa. A critical advantage of the proposed model is that it can generate, using experimentally measured values of alpha, beta and kappa, computer simulations of theoretical individual cell paths for use in evaluating the role of cell migration in specific physiological processes. We have used the model to assess MEC migration in the presence of absence of the angiogenic stimulus acidic fibroblast growth factor (aFGF). Time-lapse video was used to observe and track the paths of cells moving in various media, and the mean square displacement was measured from these paths. To test the validity of the model, we compared the mean square displacement measurements of each cell with model predictions of that displacement. The comparison indicates that the O-U process provides a satisfactory description of the random migration at this level of comparison. Using nonlinear regression in these comparisons, we measured the magnitude of random accelerations, alpha, and the velocity decay rate constant, beta, for each cell path. We consequently obtained values for the derived quantities, speed and persistence time. In control medium, we find that alpha = 250 +/- 100 microns 2h 3 and beta = 0.22 +/- 0.03h-1, while in stimulus medium (control plus unpurified aFGF) alpha = 1900 +/- 720 microns 2h-3 and beta = 0.99 +/- 0.37h-1.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1885679 TI - Interactions between mesoderm cells and the extracellular matrix following gastrulation in the chick embryo. AB - In the gastrulating chick embryo, the mesoderm cells arise from the epiblast layer by ingression through the linear accumulation of cells called the primitive streak. The mesoderm cells emerge from the streak with a fibroblastic morphology and proceed to move away from the mid-line of the embryo using, as a substratum, the basement membrane of the overlying epiblast and the extracellular matrix. We have investigated the roles of fibronectin and laminin as putative substrata for mesoderm cells using complementary in vivo and in vitro methods. We have microinjected agents into the tissue space adjacent to the primitive streak of living embryos and, after further incubation, we have examined the embryos for perturbation of the mesoderm tissue. These agents were: cell-binding regions from fibronectin (RGDS) and laminin (YIGSR), antibodies to these glycoproteins, and a Fab' fragment of the antibody to fibronectin. We find that RGDS, antibody to fibronectin, and the Fab' fragment cause a decrease in the number of mesoderm cells spread on the basement membrane, and a perturbation of cell shape suggesting locomotory impairment. No such influence was seen with YIGSR or antibodies to laminin. These results were extended using in vitro methods in which mesoderm cells were cultured in fibronectin-free medium on fibronectin or laminin in the presence of various agents. These agents were: RGDS; YIGSR; antibodies to fibronectin, fibronectin receptor, laminin and vitronectin; and a Fab' fragment of the fibronectin antiserum. We find that cell attachment and spreading on fibronectin is impaired by RGDS, antiserum to fibronectin, the Fab' fragment of fibronectin antiserum, and antiserum to fibronectin receptor. The results suggest that although the RGDS site in fibronectin is important, it is probably not the only fibronectin cell-binding site involved in mediating the behaviour of the mesoderm cells. Cells growing on laminin were perturbed by YIGSR, RGDS and antibodies to laminin, suggesting that mesoderm cells are able to recognise at least two sites in the laminin molecule. We conclude that the in vivo dependence of mesoderm cells on fibronectin is confirmed, but that although these cells have the ability to recognise sites in laminin as mediators of attachment and spreading, the in vivo role of this molecule in mesoderm morphogenesis is not yet certain. PMID- 1885681 TI - Morphological expression of cell transformation induced by c-Ha-ras oncogene in human breast epithelial cells. AB - The present work describes the morphological pattern of c-Ha-ras-transformed MCF 10A cells. This immortalized human breast epithelial cell line was transfected utilizing the calcium phosphate technique with pHo6 containing the neomycin resistant gene alone, and identified as MCF-10Aneo, or with the normal Ha-ras proto-oncogene, MCF-10AneoN, or with the human p24 mutated Ha-ras oncogene, MCF 10AneoT cells. These three cell types were studied by scanning and transmission electron microscopy at passages 6 and 20 post-transfection. It was observed that transfection with the plasmid alone did not induce any morphological changes in MCF-10A cells. These two cell types exhibited those features that are characteristic of mammary epithelial cells in culture. Amplification of the normal c-Ha-ras oncogene by transfection induced significant morphological changes at the level of cell shape, from flat to cuboidal, and cytoplasmic changes suggesting a more metabolically active cell. These changes were made more prominent by transfection with the mutated ras oncogene, which induced stratification of a cuboidal epithelium and increase in cell size as well as a more pleomorphic nuclear and cytoplasmic appearance. Distinctive features induced by the mutated c-Ha-ras oncogene were the lengthening and thickening of cell surface microvilli, formation of blebs and emission of filopodial projections. It induced cytoplasmic changes consisting of formation of intracellular lumina, and increased the number of lysosomes, mitochondria and glycogen content, significantly decreasing the number of intermediate filaments. This is the first report that describes the morphological characteristics of a human breast epithelial cell line transformed in vitro. PMID- 1885680 TI - Enhanced assembly of basement membrane matrix by endodermal cells in response to fibronectin substrata. AB - Basement membranes are complex extracellular matrices contributing to the regulation of growth, migration and differentiation of many cell types. However, little is known about the mechanisms regulating the deposition and assembly of basement membrane from its constituents. We have investigated the role of extracellular matrix molecules in the control of basement membrane matrix assembly by cultured endodermal (PFHR-9) cells. In the presence of fibronectin depleted serum, substrata of fibronectin or laminin induced an increase in deposition of laminin, type IV collagen and proteoglycans by PFHR-9 cells, in comparison to cells adherent to type I collagen-coated, vitronectin-coated or uncoated substrata. Direct effects of fibronectin or laminin on the degree of cell spreading or rate of proliferation were not responsible for enhanced matrix deposition. The effect did not result from a redirection of basement membrane components to the matrix, since there was no decrease in matrix constituents released to the culture supernatants. Furthermore, the synthesis and release of other molecules that are not basement membrane constituents was unaltered in response to different extracellular matrix substrata. Experiments with fibronectin fragments showed that a 105 x 10(3) Mr 'cell'-binding domain (containing the cell attachment sequence Arg-Gly-Asp-Ser) was an important contributor to enhanced matrix deposition, while the N-terminal 29 x 10(3) Mr heparin-binding domain also contributed to the effect, particularly with respect to heparan sulfate proteoglycan deposition. It seems that fibronectin has a dual role of action in promoting basement membrane matrix assembly, through direct cell surface interactions, and through the binding of fibronectin to other matrix components that may nucleate or stabilize the matrix assembly. PMID- 1885682 TI - Automated aflatoxin analysis of foods and animal feeds using immunoaffinity column clean-up and high-performance liquid chromatographic determination. AB - A commercially available system is described for the fully automated clean-up and high-performance liquid chromatographic (HPLC) analysis of aflatoxins in foods and animal feeds. The system marketed primarily for handling solid-phase extraction columns has modified software to facilitate use with immunoaffinity columns. Sample extract clean-up followed by injection onto an HPLC column with post-column iodination and fluorescence detection is carried out completely unattended. A coefficient of variation of 5.1% for aflatoxin B1 analysis was obtained, and the accuracy of the system was demonstrated by the analysis of peanut butter certified reference material. PMID- 1885683 TI - High-performance liquid chromatography of sulfur-containing amino acids and related compounds with amperometric detection at a modified electrode. AB - Organic disulfides generally are not oxidized at bare electrodes under conditions that are suited to routine amperometric detection, and thiols are typically oxidized in a manner that leads to partial blockage of the surface. Modification of a carbon electrode with a film of Ru(III,IV) oxide stabilized with cyanocross links permits the amperometric detection of cystine, cysteine, glutathione, methionine, and glutathione disulfide under conditions compatible with their chromatographic separation on a strong cation-exchange column. Detection limits of 0.2-0.6 microM and linear dynamic ranges of at least 1-50 microM were obtained. The electrode was stable for at least 11 days with a pH 1 citrate, phosphate mobile phase. PMID- 1885684 TI - High-performance liquid chromatographic separation of racemic and diastereomeric mixtures of 2,4-pentadienoate-iron tricarbonyl derivatives. AB - beta-Cyclodextrin chiral stationary phase facilitates the chiral separation of the (+/-)-methyl-5-formyl-2,4-pentadienoate-iron tricarbonyl (1) racemic mixture. The separation of oxazolidine derivatives 2 and 3 diastereomers were achieved with a C18 column but the compounds underwent in-column hydrolysis to give (-)- and (+)-1, respectively. This hydrolysis was exploited for the determination of 2 and 3 by the beta-cyclodextrin column, namely 2 and 3 were initially and completely hydrolyzed in the column to give (-)- and (+)-1 and this racemic mixture was then separated by this chiral column. PMID- 1885685 TI - Dual-column high-performance liquid chromatographic cleanup procedure for the determination of polychlorinated dibenzo-p-dioxins and dibenzofurans in fish tissue. AB - A high-performance liquid chromatographic cleanup procedure employing normal phase alumina and carbon--silica separations was developed for isolating polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) from other polychlorinated pollutants present in fish tissue. The method utilizes a column switching step where the dioxins and furans are trace enriched onto a carbon silica column as they are eluted from the alumina column. Interfering components such as polychlorinated biphenyls and chlorinated diphenyl ethers elute through the carbon--silica column. The PCDDs and PCDFs are subsequently recovered by backflushing the carbon--silica column using toluene. PMID- 1885686 TI - Determination of sorbic acid in margarine and butter by high-performance liquid chromatography with fluorescence detection. AB - A procedure is reported for the separation and determination of sorbic acid, as a derivative of 4-bromoethyl-6,7-dimethoxycoumarin, by reversed-phase high performance liquid chromatography with fluorescence detection using enanthic acid as an internal standard. Sorbic acid, separated from samples of commercial margarine and butter by steam distillation, was evaluated using the proposed procedure and by UV absorption and visible spectrophotometric methods (AOAC). The preparation of the calibration graph and the determination of sorbic acid with the visible spectrophotometric method was improved. The sorbic acid content determined using UV and visible spectrophotometric methods was higher than that obtained with the reversed-phase performance liquid chromatographic method owing to the presence of interfering substances in the samples. The range of recovery and the precision of the proposed method and the reference methods are also reported. PMID- 1885687 TI - Determination of bovine butterfat triacylglycerols by reversed-phase liquid chromatography and gas chromatography. AB - Triacylglycerols (TGs) from a sample of summer butterfat (bovine milk) were analysed and fractionated by reversed-phase liquid chromatography (RPLC). Fatty acid and TG composition of eac of the 47 RPLC fractions ranging from 0.1 to 6.9% were determined by capillary gas chromatography. The data were used together to determine the quantitative composition of the molecular species of TGs. A large number of TG species, accounting for 80% of the total, could be unequivocally identified and individually determined. The combination of the chromatographic methods used proved to be a powerful and accurate approach for the determination of molecular species of TGs in a complex fat, but also a difficult and time consuming task. PMID- 1885688 TI - High-performance liquid chromatography packing materials for the analysis of small molecules in biological matrices by direct injection. AB - The increasing demand on high-performance liquid chromatography to resolve mixtures of closely related components in complex biological matrices in less time with higher precision has led to the development of a variety of new high performance liquid chromatography columns, which eliminate the need for sample preparation. These packings isolate small molecules from biological macromolecules on direct sample injection by exerting two separation mechanisms. They allow elution of all sample macromolecules with high recovery in one peak at the extraparticulate void, because of size-exclusion interactions with hydrophilic outer particulate surfaces. Simultaneously, these packings allow permeation and partitioning of small molecules on bonded-phases which are protected from contamination by macromolecules. The names given to these new packings include "internal surface reversed-phase", "shielded hydrophobic phase", "semipermeable surface", "dual zone material" and "mixed-functional phases". The fundamental principles behind each of the design concepts are reviewed, and applications are cited. PMID- 1885689 TI - Coated hydrophilic polystyrene-based packing materials. AB - A very hydrophilic high-performance liquid chromatographic base support was created from microparticulate, macroporous poly(styrene-divinylbenzene) beads. An organic monomer containing cross-linking functionalities was coated on the poly(styrene-divinylbenzene), followed by a catalyzed cross-linking reaction. The coatings formed contain only stable chemical bonds (e.g., C-C, C-O-C), and easily derivatized hydroxyl moieties. This coated base support was evaluated for hydrophilicity, chemical stability, solvent compatibility, rigidity, and irreversible adsorption. Derivatives of the coated base support were made and applied in various modes of chromatography. PMID- 1885690 TI - Semipermeable-surface reversed-phase media for high-performance liquid chromatography. AB - Polyoxyethylene was both adsorbed hydrophobically (through the use of non-ionic surfactants) and covalently bonded to reversed-phase high-performance liquid chromatographic packings, thereby establishing a semipermeable hydrophilic layer over the alkylsilane surface. This layer restricts proteins from adsorbing to the alkylsilane phase while permitting penetration and chromatographic separation of small molecules. Biological fluids containing low-molecular-weight analytes may be injected directly, without sample pretreatment or the use of micellar eluents. In the case of adsorbed coatings, surfactant loading was determined primarily by the surface area (over the reversed phase) occupied by the polyoxyethylene head group. Semipermeability of the hydrophilic layer was demonstrated by observing changes in retention of both small molecules and proteins with increasing eluent ionic strength. Coated column stability was evaluated with regard to cumulative eluent volume and repeated serum injections. PMID- 1885691 TI - Liposome chromatography: liposomes immobilized in gel beads as a stationary phase for aqueous column chromatography. AB - Liposomes have been used as a stationary phase for column chromatography with an aqueous mobile phase. They were immobilized in the pores of carrier gel beads by two methods: (A) hydrophobic ligands were coupled to the matrix of gel beads, which then were packed into a column and liposomes were applied and became associated with the ligands by hydrophobic interaction; and (B) phospholipids and detergent were dialysed in the presence of gel beads; many of the liposomes that formed in the pores of the beads were sterically immobilized by the gel matrix. Proteoliposomes containing red cell glucose transport protein in the lipid bilayers were immobilized in a column by method A. This column retained D-glucose longer than L-glucose. In contrast to L-glucose, D-glucose was transported into and out of the immobilized liposomes, causing an increased retention. Liposomes with (stearylamine)+ or (phosphatidylserine)- in their lipid bilayers were immobilized by method B and the gel beads were packed into a column. A protein of opposite charge was applied in excess. Under suitable conditions, the protein molecules became close-packed on the liposome surfaces. Ion-exchange chromatographic experiments with proteins showed that these sterically immobilized liposomes were also stable enough to be used as a stationary phase. The loss of lipids was 5-23% in the first run at high protein load and with sodium chloride gradient elution but was lower in subsequent runs. It is proposed that water-soluble molecules can be separated and their interactions with liposome surfaces studied by chromatography on immobilized liposomes in detergent free aqueous solution. Membrane proteins can be inserted and ligands can be anchored in the lipid bilayers for chromatographic purposes. PMID- 1885693 TI - Determination of halofuginone in feedstuffs by the combination of capillary isotachophoresis and capillary zone electrophoresis in a column-switching system. AB - A method has been developed for the determination of the coccidiocidic drug halofuginone in feedstuff concentrates which is based on the combination of capillary isotachophoresis and capillary zone electrophoresis in the column switching mode. The high load capacity of the isotachophoretic step and high sensitivity of the zone electrophoretic step enabled analysis of up to 25 microliters of sample solution containing as little as 10(-8) M halofuginone with excellent reproducibility (R.S.D. about 1%). Attention was paid to the possibility of the existence of transient local isotachophoresis in the zone electrophoretic step, and experimental and theoretical methods of revealing zones migrating isotachophoretically in the background electrolyte were shown. PMID- 1885692 TI - Hydrophilic shielding of hydrophobic, cation- and anion-exchange phases for separation of small analytes: direct injection of biological fluids onto high performance liquid chromatographic columns. AB - Shielded hydrophobic phases (SHPs) have an external hydrophilic network that prevents larger protein molecules from interacting with hydrophobic zones. Smaller analytes are not sterically hindered from interacting with the hydrophobic zones and are retained. This mechanism allows the separation of the proteins from the analytes of interest. SHPs have been shown to be useful for the direct-injection analysis of drugs in biological fluids. In this paper, two kinds of shielded phases are discussed: bonded micellar phases and embedded polymeric phases. For some compounds of interest, the hydrophobic retention and selectivity is insufficient to obtain the desired resolution. To increase selectivity without affecting protein exclusion, shielded phases were prepared with ion-exchange groups added to the hydrophobic zones. Such modified phases with cation-exchange and anion-exchange capabilities were examined for additional selectivities. Usage of these additional selectivities will be demonstrated to achieve better analysis and resolution for basic, acidic, and neutral compounds. PMID- 1885695 TI - Isotachophoretic determination of 2-5A phosphodiesterase. AB - Together with 2-5A synthetase and ribonuclease L, 2-5A phosphodiesterase belongs to the 2-5A system, which plays an important role in the action of interferon. Analytical capillary isotachophoresis was used for the determination of 2-5A phosphodiesterase activity. Enzyme assay was optimized using snake venom phosphodiesterase as a source of 2-5A phosphodiesterase activity. The 2-5A trimer core was used as a substrate. Enzyme activity was determined in time- and concentration-dependent reactions. In addition, 2-5A phosphodiesterase activity was determined in lysates of mononuclear blood cells. PMID- 1885694 TI - Analytical isotachophoresis in biological monitoring of exposure to industrial chemicals. AB - Isotachophoretic methods for the determination of compounds of interest in biological monitoring are reviewed. The analytes are charged biotransformation products such as acids or amines. Comparisons are made between isotachophoretic methods and other techniques regarding sensitivity, need for preseparation or derivatization and similar technical aspects. PMID- 1885697 TI - The use of pulsed amperometry combined with ion-exclusion chromatography for the simultaneous analysis of ascorbic acid and sulfite. AB - Initial attempts to monitor ascorbic acid and sulfite, in a beer matrix, by combining ion-exclusion chromatography with a pulsed amperometric detector using a single applied voltage to the platinum working electrode, were unsuccessful. Alternatively, good chromatograms for the separation of the two antioxidants were achieved utilizing a standard, amperometric cell. However, remarkably superior results were observed when this standard cell was operated in a pulsed mode and cleaning cycles were continually applied throughout the analysis. The working electrode stability and precision have been examined. Preliminary spike recovery data indicate acceptable accuracy for the method. Comparisons of this method to standard reference methods are currently ongoing. PMID- 1885696 TI - Analysis of barbiturates in human serum and urine by high-performance capillary electrophoresis-micellar electrokinetic capillary chromatography with on-column multi-wavelength detection. AB - The analysis of barbiturates in human serum (or plasma) and urine by high performance capillary electrophoresis-electrokinetic capillary chromatography with on-column fast-scanning multi-wavelength detection is discussed. The use of a buffer of ca. pH 8 and containing sodium dodecyl sulphate provides a medium suitable for fast and high-resolution separations of barbiturates. Seven barbiturates are characterized by their retention and absorption spectra between 195 and 320 nm. Comparison of these computer-stored data with those of unknown samples is shown to allow the identification of barbiturates in samples of patients undergoing pharmacotherapy and in toxicological urine and serum specimens. Three-dimensional electropherograms provide reliable information on the requirement and suitability of sample pretreatment procedures. With urine, extraction of barbiturates prior to analysis is necessary. With human serum several barbiturates, including phenobarbital, are shown to elute in an interference-free window in front of uric acid and the proteins, allowing these substances to be determined by direct sample injection. The need for multi wavelength detection over a relatively wide wavelength range as a means of peak confirmation in electrokinetic capillary analyses is demonstrated and limitations of this technique for compounds with similar retention behaviour and absorption spectra are discussed. PMID- 1885698 TI - Progress in optimization of transition metal cation chromatography and its application to analysis of silicon wafer contamination. AB - Methods are reported which yield sensitive semi-quantitative analysis of transition metal contaminants on silicon wafers. An effective extracting solution is proposed together with compatible concentrators and two eluent (column and post-column) chemistry combinations to measure ppt (10(12)) concentrations and surface densities extending into the 10(10) atoms per cm2 range. Possible applications include numerous steps in wafer and integrated circuit manufacture as well as other solid-surface analysis. PMID- 1885699 TI - Determination of saccharides in biological materials by high-performance anion exchange chromatography with pulsed amperometric detection. AB - High-performance anion-exchange chromatography (HPAEC) coupled with pulsed amperometric detection (PAD) under alkaline conditions (pH 9-13) separates aminosaccharides, neutral saccharides and glycuronic acids based upon their molecular size, saccharide composition and glycosidic linkages. Carbohydrates were extracted by utilizing 0.5 M H2SO4 (neutral monosaccharides), 0.25 M H2SO4 coupled with enzyme catalysis (glycuronic acids) and 3 M H2SO4 (aminosaccharides). Solid-phase extraction with strong cation and strong anion resins was used to partition the cationic aminosaccharides and anionic glycuronic acids and to deionize acid extracts for neutral saccharides. Separation was conducted on a medium-capacity anion-exchange column (36 mequiv.) utilizing sodium hydroxide (5-200 mM and sodium acetate (0-250 mM) as the mobile phase. The saccharides were detected by oxidation at a gold working electrode with triple pulsed amperometry. HPAEC-PAD was found superior to high-performance liquid chromatography with refractive index (RI) detection for neutral monosaccharides and aminosaccharides and to low-wavelength UV detection for glycuronic acids in terms of resolution and sensitivity. HPAEC-PAD was not subject to interferences as was the case for low UV detection (210 nm) or RI analyses and was highly selective for mono- and aminosaccharides and glycuronic acids. The use of HPAEC PAD was applied for the determination of the saccharide composition of organic materials (plant residues, animal wastes and sewage sludge), microbial polymers and soil. PMID- 1885700 TI - Determination of free nitrilotriacetic acid in environmental water samples by ion chromatography with potentiometric and amperometric detection with a copper electrode. AB - An ion-chromatographic method is described for the analysis of free nitrilotriacetic acid in water samples. Separations are achieved on a polymer based anion-exchange column with 6 mM nitric acid as eluent. Both potentiometric and amperometric detection have been applied using metallic copper as the indicator electrode. Detection limits are at about 500 ng injected in the potentiometric mode and 100 ng in the amperometric mode. On-line sample preconcentration is possible for volumes up to 2 ml of river water samples. The response of the detector to other aminopolycarboxylic and aminopolyphosphonic acids has been investigated. PMID- 1885701 TI - Azide determination in protein samples by ion chromatography. AB - Sodium azide is used as an anti-fungal agent in protein samples in the health related scientific community. Due to its toxic nature, monitoring of the azide level in proteins used in scientific research is necessary. Ion-exchange chromatography has been used to quantitate azide levels in protein samples. Anion exchange methodology is described which allows for the separation of azide from various common anions found in analytical grade protein sample matrices. The analytical system described utilizes a polymer [poly(styrene-divinylbenzene)] stationary phase which has been surface sulfonated followed by the binding of the aminated latex bead active ion-exchange sites (Dionex, AS4A column). Sodium tetraborate is used as the weak anion-exchange mobile phase. A vendor ion exchange column comparison is made along with eluent composition and selection studies. Method validation data are presented including: calibration plots for external standardization, limit of detection and method recovery. Various types of proteins are assayed using the described method. PMID- 1885702 TI - Determination of dissolved hexavalent chromium in industrial wastewater effluents by ion chromatography and post-column derivatization with diphenylcarbazide. AB - A proposed EPA method for the determination of dissolved hexavalent chromium in drinking water, groundwater and industrial wastewater effluents was developed using existing ion chromatographic techniques. Two solid waste matrices were briefly investigated. Aqueous samples were passed through a 0.45-micron filter and the filtrate was either (1) left unadjusted, (2) adjusted to pH 8 or (3) adjusted to pH 10 prior to analysis by ion chromatography. The method detection limits were 0.3-0.4 micrograms/l. When analyzed within 24 h, the two pH levels and the unadjusted sample yielded ca. 100% recovery of spikes. No oxidation of trivalent chromium to hexavalent chromium was observed at pH 7, 8 or 10 when aqueous samples were spiked with 50 mg/l Cr(III). PMID- 1885703 TI - Analysis of anion constituents of urine by inorganic capillary electrophoresis. AB - Inorganic capillary electrophoresis (ICE) is a new separations technology which melds the technique of classical electrophoresis with the separations approach of ion chromatography. Matrices which have been difficult to deal with using ion chromatography have proven amenable to analysis by ICE. The simultaneous analysis of weak acid anions, oxalate and citrate and inorganic anions, chloride, sulfate, nitrate, phosphate and carbonate in diluted urine was achieved using ICE. The determination of the oxyanions of arsenic (i.e. arsenite and arsenate) in urine was also performed. PMID- 1885705 TI - Rapid and accurate high-performance liquid chromatographic method for the determination of 3-methylindole (skatole) in faeces of various species. AB - A rapid method for the determination of skatole (3-methylindole) in faeces by reversed-phase high-performance liquid chromatography is described. Samples of 0.5 g were extracted with 2 ml of methanol. The extract was purified on Amberlite XAD-8. The lower limit of detection was 2.5 ng per injection (0.2 microgram/g faeces). The mean recovery of skatole was 95%, and the mean coefficients of variation were 7.0% (intra-assay) and 11.8% (inter-assay). Skatole concentrations were clearly lower in faeces from ruminants (average 2.6 micrograms/g for goat, sheep and cattle) than in those from monogastrics. Mean concentrations in human samples were 15.5 micrograms/g, and 10 micrograms/g in mature domestic pigs. An effect of the anabolic status on skatole concentrations in faeces of pigs is likely. PMID- 1885704 TI - Fluorimetric and high-performance liquid chromatographic determination of D lactate in biological samples. AB - D-Lactate in biological samples was converted into a strongly fluorescent substance in a one-vial reaction. It was first converted into the pyruvate hydrazone in the presence of D-lactate dehydrogenase, an NADH-reoxidation system using diaphorase, D,L-6,8-thioctamide and hydrazine. This hydrazone was then converted into 2-hydroxy-6,7-dimethoxy-3-methylquinoxaline by 1,2-diamino-4,5 dimethoxybenzene in 1 M hydrochloric acid, and the quinoxaline was extracted and measured fluorimetrically at 432 nm (excitation at 365 nm). The calibration curve for D-lactate was linear up to at least 100 nmol/ml of the assay mixture, with a determination limit of 2 nmol/ml. The quinoxaline was also analysed by high performance liquid chromatography with fluorimetric detection. The calibration curve for D-lactate was linear from 500 fmol to 75 nmol in the reaction mixture. This method was 4000 times more sensitive than the fluorimetric method, and could determine D-lactate in blood plasma volumes of less than 1 microliter. PMID- 1885706 TI - Ion-sensitive field effect transistor as a monovalent cation detector for ion chromatography and its application to the measurement of Na+ and K+ concentrations in serum. AB - An ion-sensitive field effect transistor, which is a small potentiometric ion sensing probe, was applied as a detector in the ion chromatography of alkali metal cations. The cation-sensing transistor was prepared by coating the gate part of the probe to form a poly(vinyl chloride) matrix membrane containing tetranactin, which enables detection of alkali-metal ions such as Na+, K+, Rb+, and Cs+. To be able to analyse amounts less than 1 microliter and make full use of the small ion-sensing probe, we constructed a miniature cation-exchange separation column (support 10 microns polystyrene) with a PTFE tube (20 mm x 1.5 mm I.D. x 2.1 mm O.D). As an application of the system, Na+ and K+ concentrations in serum were determined. The analytical results for these two cations were good agreement with those obtained by flame photometry. PMID- 1885707 TI - Determination of morphine and 6-acetylmorphine in plasma by high-performance liquid chromatography with fluorescence detection. AB - A method is described for the simultaneous determination of morphine and 6 acetylmorphine in small volumes of human plasma by normal-phase high-performance liquid chromatography using solid-phase extraction, dansyl derivatisation and fluorescence detection. The lower limits of quantitation in a 0.1-ml plasma sample are 10 ng/ml for morphine and 25 ng/ml for 6-acetylmorphine. The method has been applied to determine concentrations of morphine and 6-acetylmorphine in plasma samples from premature babies administered an intravenous infusion of diamorphine. PMID- 1885708 TI - Application of an ovomucoid-conjugated polymer column for the enantiospecific determination of chlorprenaline concentrations in plasma. AB - An ovomucoid-conjugated polymer column was prepared for the liquid chromatographic resolution of racemic compounds. The column showed strong retention of acidic solutes, a characteristic attributed to the structure of the stationary phase support gel. Although the efficiency of the column was lower than that of an ovomucoid-conjugated silica gel column, enantiospecific chlorprenaline determination in plasma was achieved with solute amounts from 1.0 ng to 0.1 microgram. PMID- 1885709 TI - Analysis of chloramphenicol residues in swine tissues and milk: comparative study using different screening and quantitative methods. AB - Both screening and quantitative methods for chloramphenicol residues in swine tissues and milk were compared, using samples from animals treated with chloramphenicol. For screening purposes a previously developed streptavidin biotin enzyme-linked immunosorbent assay and a commercially available immunochemical card test were used. For quantitative purposes two previously developed high-performance liquid chromatographic procedures were applied using antibody-mediated clean-up and solid-phase extraction. Some improvements in both methods were also described. The results obtained with the screening tests and those obtained with the quantitative methods correspond well with each other. Using a combination of these methods, an effective control of residues of chloramphenicol can be performed in milk from the 1 microgram/kg level and in swine tissues from the 10 micrograms/kg level. PMID- 1885710 TI - Fluorimetric determination of mexiletine in serum by high-performance liquid chromatography using pre-column derivatization with fluorescamine. AB - A simple, specific and sensitive micro-scale method for the assay of the antiarrhythmic agent mexiletine in human serum is described. The method uses high performance liquid chromatography, with pre-column fluorimetric derivatization by fluorescamine. Following extraction with diethyl ether, mexiletine and 4 methylmexiletine (an internal standard) were derivatized with fluorescamine under weakly alkaline condition (pH 9.0) and chromatographed on a reversed-phase column with aqueous methanol-2-propanol as the mobile phase. The two fluorescent derivatives of mexiletine and the internal standard were separated as clear single peaks, and no interfering peaks were observed on the chromatograms. The detection limit for mexiletine was 0.005 micrograms/ml from only 100 microliters of serum, and the calibration curves in the range 0.01-5 micrograms/ml were linear, with an overall coefficient of variation of less than 5%. The analytical recovery of a known amount of mexiletine added to serum was almost 100%. This method proved to be effective in the rapid monitoring of the serum concentrations in patients who received this potent antiarrhythmic drug. PMID- 1885711 TI - Simultaneous determination of urinary creatinine and aromatic amino acids by cation-exchange chromatography with ultraviolet detection. AB - A cation-exchange chromatographic procedure for the simultaneous determination of urinary creatinine and aromatic amino acids is described. Creatinine and amino acids were separated from organic acids and/or neutral species in urine by using a preparative cation-exchange resin column. A column packed with a cation exchange resin of low capacity was used for the analytical separations. The elution of creatinine and aromatic amino acids was monitored at 210 nm by means of an ultraviolet detector. The relationships between concentration and peak heights were reproducible with a coefficient of variation of less than 2%, and were linear from 5 to 200 microM for each compound. Overall recoveries of the analytes were more than 95%. The method was applied to the analysis of urine of patients with disorders of amino acid metabolism, such as phenylketonuria. The concentration ratios of phenylalanine to creatinine in the patients' urine were accurately and easily determined, and were quite different from those in the urine of healthy newborns. PMID- 1885712 TI - Reversed-phase high-performance liquid chromatography of tenuazonic acid and related tetramic acids. AB - A reversed-phase high-performance liquid chromatographic system for the determination of the fungal toxin, tenuazonic acid, (5S,8S)-3-acetyl-5-sec. butyltetramic acid, is described. The system utilizes a column packed with deactivated end-capped C18 silica with a high carbon load to overcome the problem of poor chromatographic performance of this beta-diketone on reversed-phase liquid chromatography which previously necessitated the use of anion-exchange, ligand-exchange or ion-pairing methods. The reversed-phase system allows the separation of tenuazonic acid from its (5R,8S)-diastereomer, allo-tenuazonic acid and was applied to the detection of tenuazonic acid in cultures of Alternaria alternata and Phoma sorghina. By means of diode-array ultraviolet detection, (5S) 3-acetyl-5-isopropyltetramic acid was observed in extracts of culture material. This metabolite was purified using the analytical reversed-phase system and was identified by 1H and 13C nuclear magnetic resonance spectroscopy. PMID- 1885713 TI - Comparison of sulphur-mode and tin-mode flame photometric detectors for the gas chromatographic determination of organotin compounds. AB - A comparison of sulphur-mode (393 nm) and tin-mode (610 nm) flame photometric detectors for the gas chromatographic determination of butyl- and phenyltin compounds is described. The chromatographic peaks of the butyl- and phenyltin compounds were well separated, and high sensitivity was achieved in both modes; however, the tin-mode was more specific for tin compounds than the sulphur-mode. The absolute detection limits with the sulphur-mode and the tin-mode were 3.9-7.6 pg and 2.6-5.1 pg as tin, respectively. The application of the tin-mode gas chromatographic method to the determination of organotin compounds in fish is presented. For this application, organotins are extracted (as chloride) with hydrochloric acid and n-hexane-benzene (3:2, containing 0.05% tropolone) and the extracts are pentylated by a Grignard reagent prior to gas chromatography. The absolute recoveries of butyl- and phenyltin compounds added to fish samples ranged from 68.5 to 84.4% (the coefficients of variation were less than 6.6% for all substances, n = 8). Significant amounts of three organotin compounds (di- and tributyltin and triphenyltin) in fish samples were detected by this method. This technique may have application for other organotin compounds and the monitoring of butyl- and phenyltin compounds in the environment. PMID- 1885714 TI - Analysis of serum methylmalonic acid for the determination of cobalt deficiency in cattle. AB - An improved method has been developed and validated for the determination of methylmalonic acid (MMA) in serum to determine cobalt deficiency in cattle. Serum samples were extracted with ethyl acetate and derivatised to form the propyl esters using 14% boron trifluoride-propanol derivatising reagent. Derivatised samples were analysed by capillary gas chromatography using split injection, a DB 17 30 m x 0.25 mm I.D. capillary column and flame ionisation detection. The detection limit for the method was 0.5 mumol/l and precision, determined by replicate analyses of spiked serum samples, was less than 2% relative standard deviation. When cobalt deficiency is defined as a MMA serum concentration of more than 2 mumol/l, the method was able to detect clinical deficiency of cobalt in animals with symptoms such as "coasty" coats and low weight gain. PMID- 1885715 TI - Simple and sensitive determination of plasma N tau-methylhistidine by high performance liquid chromatography using pre-column derivative formation with o phthalaldehyde-2-mercaptoethanol. AB - A simple, rapid and sensitive assay method for plasma N tau-methylhistidine by isocratic high-performance liquid chromatography has been developed. The deproteinized plasma was treated with o-phthalaldehyde-2-mercaptoethanol. The derivatives were separated on a LiChrospher 100 RP-18 column within 10 min. The detection limit for N tau-methylhistidine was 0.5 pmol. The plasma N tau methylhistidine content of beef cattle and dairy cows was 0.038 +/- 0.004 and 0.017 +/- 0.002 nmol/ml/kg, respectively. PMID- 1885716 TI - Simultaneous determination of trimipramine and its major metabolites by high performance liquid chromatography. AB - Trimipramine is a tricyclic antidepressant drug often assayed by gas chromatographic or gas chromatographic-mass spectrometry techniques. A high performance liquid chromatographic method with electrochemical detection is described for the assay of trimipramine and its major metabolites, monodesmethyltrimipramine and 2-hydroxytrimipramine, in plasma. The method is sensitive, accurate and robust and thus suitable for routinely assaying samples following single doses of trimipramine to man. The assay was applied to plasma samples obtained following a single 50-mg dose of trimipramine to healthy volunteers. PMID- 1885717 TI - High-performance liquid chromatographic determination of glyphosate and (aminomethyl)phosphonic acid in human serum after conversion into p toluenesulphonyl derivatives. AB - We have developed a simple, highly sensitive and fast assay method for determining glyphosate and its major metabolite, (aminomethyl)phosphonic acid (AMPA), in serum by high-performance liquid chromatography with ultraviolet detection. Both compounds were successfully extracted with an anion-exchange resin column and allowed to react with p-toluenesulphonyl chloride. The detection limits were 0.3 microgram/ml for glyphosate and 0.2 microgram/ml for AMPA. Recoveries of glyphosate and AMPA spiked to serum were ca. 75% and ca. 88%, respectively. We are convinced that this procedure, in practice, allows medical examiners to analyse both compounds in the serum of poisoned patients within a short time. PMID- 1885718 TI - Rapid and sensitive method for the determination of albendazole and albendazole sulphoxide in biological fluids. AB - A sensitive and selective reversed-phase high-performance liquid chromatographic method for the determination of albendazole and its active metabolite albendazole sulphoxide in plasma has been developed. It involves single-step extraction of plasma with dichloromethane, evaporation of the solvent and chromatography on a muBondapak phenyl column with a mobile phase of water containing 1% (v/v) triethylamine-methanol-acetonitrile (70:10:20, v/v) at pH 3.1. Run time is 12 min. The assay satisfies all of the criteria required for use in clinical pharmacokinetic studies and possesses important advantages, notably speed and expense, over current methods. PMID- 1885719 TI - Sensitive determination of buspirone in serum by solid-phase extraction and two dimensional high-performance liquid chromatography. AB - A selective and sensitive determination of buspirone in serum by high-performance liquid chromatography is described. The procedure is based on separation on a C18 column. A solid-phase extraction procedure is used for sample clean-up. The retention on the first column is based on the hydrophobic interaction of buspirone with the stationary phase, and the retention on the second column is based on ionic interactions due to the presence of sodium lauryl sulphate in the mobile phase as well as hydrophobic interaction. This allows for good separation of buspirone from impurities and consequently allows lower detection limits than previously reported for liquid chromatographic methods. Detection by ultraviolet absorbance gives a detection limit of 0.2 ng/ml. PMID- 1885720 TI - Quantitation of a novel antiemetic (ADR-851) in plasma and urine by reversed phase high-performance liquid chromatography with fluorescence detection. AB - A sensitive and specific bioanalytical method for quantitation of a novel antiemetic (ADR-851) in plasma and urine has been developed and validated. The drug and internal standard (metoclopramide) are extracted from the plasma matrix by solid-phase extraction on cyanopropyl bonded-phase columns. After extraction, samples are separated by isocratic reversed-phase high-performance liquid chromatography. The parent drug, internal standard and a yet unidentified metabolite are detected by fluorescence. The method requires 1.0 ml of plasma or 0.1 ml of urine and has a lower limit of quantitation of 2 ng/ml with 10.9% relative standard deviation (R.S.D.). Method linearity has been established over a 2-800 ng/ml range when 1.0 ml of plasma is used. The intra- and inter-day imprecisions for the method are typically better than 6% and 11% R.S.D., respectively, in both plasma and urine over the entire dynamic range. The pooled estimate of bias is less than 5% and attests to the excellent accuracy. PMID- 1885721 TI - Determination of heat-exposure effects on the concentration of catecholamines in bovine plasma and milk. AB - A reversed-phase high-performance liquid chromatographic method with electrochemical detection has been adapted for the determination of picogram concentrations of norepinephrine and epinephrine in bovine plasma and milk. This method has been used to monitor the levels of these catecholamines when lactating cows are exposed to heat stress under controlled conditions. In response to heat stress, epinephrine concentrations in milk and plasma were similar. However, norepinephrine concentrations in milk were one tenth of that in plasma. PMID- 1885722 TI - Automated determination of neuroactive acidic sulphur-containing amino acids and gamma-glutamyl peptides using liquid chromatography with fluorescence and electrochemical detection. AB - A column liquid chromatographic method is presented for the determination of trace levels of acidic sulphur-containing amino acids and gamma-glutamyl di- and tripeptides in microdialysates sampled from rat brain in vivo. Automated precolumn derivatization was performed with o-phthaldialdehyde-beta mercaptoethanol. The derivatives were separated by reversed-phase liquid chromatography with electrochemical and fluorescence detection. The mean relative standard deviation (n = 10) was 1.03 and 4.59% for retention times and peak heights, respectively. The mean correlation coefficient of linearity (r) was 0.9982 in the range 4.5-450 pmol (n = 15), and the lowest detectable amount was 200 fmol for the homocysteinesulphinic acid derivative, (k' = 5.4, at a signal-to noise ratio of 3). A microcolumn electrochemical detection method, developed for volume-limited samples, produced a fifteen-fold increase in mass sensitivity. Neurochemical applications using microdialysis in vivo are presented. PMID- 1885723 TI - Chromatographic and electrophoretic studies of circulating immune complexes in plasma. AB - The protein nature of soluble immune complexes from fresh plasma was studied by combining several analytical biochemical techniques. Free immunoglobulins (Ig) G were separated from larger immune complexes by gel permeation chromatography. In a second step, immune complexes, free IgA and IgM were isolated by protein-A and protein-G affinity chromatography and analysed by two-dimensional gel electrophoresis. Sixteen plasma samples from healthy donors were analysed and evaluated visually. Their protein profiles on the gels turned out to be similar, showing only slight quantitative differences. In one case, additional proteins were detected. To prove the ability of the method, immune complexes were analysed from four plasma samples that showed macro creatine kinase type 1, a complex formation between creatine kinase BB and IgG. This methodology can be used for the examination of immune complexes of unknown protein composition in serum or plasma. PMID- 1885724 TI - Study of the mechanism of the photoisomerization and photooxidation of bilirubin using a model for the phototherapy of hyperbilirubinemia. AB - Liquid chromatography was employed for a study of photochemical degradation of bilirubin in the complex with human albumin, using a model system in the presence of riboflavin. The concentrations of bilirubin, the photoisomers and biliverdin were monitored. The reaction mechanism was verified using a quantified mathematical model and was represented by a reaction scheme. Photoisomerization is the initial process, followed by photooxidation to degradation products of the tetrapyrrole skeleton, with formation of biliverdin as an intermediate. The blood of newborns that were irradiated for treatment of hyperbilirubinemia was studied for the sake of comparison. The effect of some biochemically important substances was followed, in view of possible inhibition of the processes. The experimental results demonstrate that riboflavin acts as a catalyst, even at the concentrations typical for its occurrence in blood. The results are discussed from the point of view of the mechanism of bilirubin degradation during phototherapy. PMID- 1885726 TI - Polymerase chain reaction: trenches to benches. PMID- 1885725 TI - Assay of synovial fluid hyaluronic acid using high-performance liquid chromatography of hyaluronidase digests. AB - A high-performance liquid chromatographic method for the determination of hyaluronic acid levels in synovial fluids has been developed. The hyaluronidase sample digests, containing an internal standard (benzoic acid), were separated on a reversed-phase octadecylsilyl column eluted with 0.01 M tetrabutylammonium phosphate-acetonitrile (83:17, v/v) at pH 7.35. The determination was made on 1:10 diluted samples, by using a calibration curve from 50 to 500 micrograms/ml of human umbilical cord hyaluronic acid. For validation, the synovial fluids were simultaneously analysed by this method and a radiometric method: a high correlation was found between the two (correlation coefficient 0.94). The proposed method can be used to determine specifically the high hyaluronic acid levels of synovial fluids without interferences from other glycosaminoglycans or non-steroidal anti-inflammatory drug treatment. PMID- 1885727 TI - Antigenic variation among strains of Chlamydia pneumoniae. AB - The antigenic profiles of six strains of Chlamydia pneumoniae were analyzed by the microimmunofluorescence test (MIF) and immunoblotting with human serum and murine monoclonal antibody. MIF-derived antibody titers in serum samples from culture-positive patients were four- to eightfold higher against autologous isolate antigen than they were against the prototype antigen strain TW-183. Sera of patients with respiratory illness that were culture negative and complement fixation positive for Chlamydia spp. produced higher titers by MIF against a strain of C. pneumoniae isolated in the area than they did against TW-183. For two of five cases, the criteria for establishing the diagnosis of acute infection were met only with use of the antigen from the local strain; TW-183 was inadequate for this purpose. Immunoblot profiles revealed antigenic differences between strains that varied with the human serologic response; i.e., unique antigens were recognized by the sera of some individuals and not by the sera of others. Using the reactivity of a genus-specific monoclonal antibody against a major outer membrane protein, we found that strain CWL-011, isolated in Atlanta, Ga., may possess a major outer membrane protein with a molecular mass between those of C. trachomatis L2 and other C. pneumoniae strains. These data provide evidence of several new and unique serotypes of C. pneumoniae and suggest that the serologic diagnosis of C. pneumoniae infection may require the use of antigens from more than one strain of this species. PMID- 1885728 TI - Model of recurrent pulmonary aspergillosis in rats. AB - Male Sprague-Dawley rats were treated with cortisone acetate and fed a low protein diet for 3 weeks. At the end of week 2, animals were infected intratracheally with 10(5) conidia of Aspergillus fumigatus H11-20. Despite discontinuation of steroids and the low-protein diet 1 week after the infection, 94% of controls died of invasive pulmonary aspergillosis within 3 weeks postinfection. When rats were treated with a single dose of 1.6 mg of aerosolized amphotericin B per kg of body weight 48 h prior to the infection, mortality was reduced to 11% within 3 weeks postinfection. Despite apparent good health and rapid weight gain, all survivors showed multiple lesions in histopathological sections of the lungs, and 10(3) to 10(4) CFU of aspergilli was recovered from cultures of their lungs. With discontinuation of immunosuppression, the infection was slowly cleared; however, when cortisone acetate was restarted during week 5, reactivation of progressive invasive pulmonary aspergillosis was observed. On the basis of these results, we conclude that a single low dose of aerosolized amphotericin B prophylaxis is effective in preventing an exogenous aspergillus infection of the lung. Additional therapy is needed to prevent recurrent infection caused by endogenous aspergilli when immunosuppression is resumed. PMID- 1885730 TI - Simplified microtiter cell culture method for rapid immunotyping of Chlamydia trachomatis. AB - Serotyping of Chlamydia trachomatis strains usually requires three to six serial passages in shell vials to attain sufficient antigen for typing procedures. To circumvent this problem, we developed a rapid low-passage method for serotyping of C. trachomatis clinical isolates. Isolates with an inclusion count of greater than or equal to 500 per well in primary isolation were inoculated directly onto cell culture monolayers in microtiter plates for typing. Primary isolates with a lower initial inclusion count were passed one to two times in shell vials until there were greater than or equal to 20 inclusions per well and were then inoculated onto plates for typing. Inclusions were grown to maturity and reacted with a panel of 17 C. trachomatis-specific monoclonal antibodies in pools. Wells were then reacted with a fluorescein isothiocyanate conjugate and read by FA microscopy, and the reaction patterns were compared with prototype strain reaction patterns to determine the serotype. By the microtiter method, we successfully typed 1,711 consecutive C. trachomatis isolates; 1,215 isolates (71%) were typed with no or with one passage. The first 209 isolates typed by the microtiter method were also typed by the dot-enzyme-linked immunosorbent assay serotyping method; 100% agreement was demonstrated among strains that were typeable by both methods. We conclude that the microtiter method is extremely useful for accurate serotyping of large numbers of isolates and requires greatly reduced technician time. PMID- 1885729 TI - Detection and enumeration of toxin-producing Pasteurella multocida with a colony blot assay. AB - Colonies of toxin-producing Pasteurella multocida were detected with peroxidase labeled monoclonal antibodies by a membrane assay. Examination of the specificity of the assay with 29 P. multocida cultures representing various geographic origins, hosts, and serotypes indicated that the test was specific for toxin producing strains. No cross-reactions were observed with Bordetella species that can be associated with P. multocida in producing diseases in animals. A single membrane could be used to assay several isolated strains for toxin production or to enumerate toxin-producing colonies in mixed cultures. Toxin-producing P. multocida colonies were detected in primary cultures; hence, the assay appears to have good potential for widespread application with clinical samples. PMID- 1885731 TI - Monoclonal antibodies specific for the phase-variant O-acetylated K1 capsule of Escherichia coli. AB - Two monoclonal antibodies, one each of the immunoglobulin M and G2b types, were produced from mouse spleen cells. These monoclonal antibodies only reacted with approximately 50% of the Escherichia coli K1 strains and not against group B meningococci. No reaction was observed after the strains were boiled. E. coli K1 strains that reacted with the monoclonal antibodies could become nonreactive after subculture. Based on these findings, we conclude that the monoclonal antibodies react with the O-acetylated K1 capsule. PMID- 1885733 TI - Fine serotyping of human immunodeficiency virus serotype 1 (HIV-1) and HIV-2 infections by using synthetic oligopeptides representing an immunodominant domain of HIV-1 and HIV-2/simian immunodeficiency virus. AB - In this study, enzyme immunoassays for detection of type-specific antibodies to human immunodeficiency viruses (HIV) were developed by using short peptides corresponding to sequences located within the immunodominant domain of the transmembrane glycoproteins of both HIV-1 and HIV-2-simian immunodeficiency virus (SIV). The assays were highly sensitive with currently available sera from various geographical areas. Furthermore, they appeared to be more specific in HIV serotyping than the Western blot (immunoblot) assay, since all of the sera were clearly discriminated as one or the other type. It was also shown that in contrast to HIV-1, the C-terminal cysteine residue (amino acid 620, SIV from captive macaques, Mm142 strain) of the HIV-2-SIV peptide is not necessary for recognition of the peptide by antibody to HIV-2. PMID- 1885732 TI - Prospective multicenter study on isolation of human immunodeficiency virus type 1 from homosexual men after seroconversion. AB - A prospective multicenter study was undertaken to isolate human immunodeficiency virus type 1 (HIV-1) from 45 homosexual men for a period of 30 months after seroconversion. Efficiency of HIV-1 isolation from peripheral blood mononuclear cells was relatively stable over time, ranging from 64% at the time of seroconversion to more than 82% after 18 months of seroconversion. However, Kaplan-Meier analysis of HIV-1 culture data indicates that the cumulative proportion of HIV-1 culture positivity at 3, 6, 12, and 18 months after seroconversion was 62, 65, 84, and 92%, respectively. No significant correlation was observed between the presence of HIV-1 p24 antigen in serum, or numbers of CD4+ and CD8+ blood lymphocytes, and HIV-1 isolation within this period of time. These data suggest that HIV-1 viremia in homosexual men gradually increases to almost 100% culture positivity by 18 months after seroconversion. PMID- 1885734 TI - Seropositivity to Helicobacter pylori: lack of association with length of hospitalization. AB - To examine the possibility of nosocomial spread of Helicobacter pylori, a serosurvey (n = 238) was conducted at Perry Point Department of Veterans Affairs Medical Center, an institution providing both acute and chronic care. We hypothesized that if significant nosocomial transmission was occurring, seropositivity (as measured by enzyme-linked immunosorbent assay [ELISA]) would correlate with length of stay in the facility. Whether treated as a continuous or dichotomous variable, the ELISA results did not correlate significantly with length of stay even after adjustments were made for age, race, antibiotic use, gastrointestinal instrumentation, and diagnoses by using multiple-regression models. Age was found to be a significant risk factor for a higher ELISA optical density value. A history of chronic obstructive pulmonary disease was significantly protective among internal medicine ward patients in adjusted analysis; black race was a significant risk factor among psychiatry ward patients. Our results confirm the association of H. pylori infection with age but provide no indication that extended hospitalization is a risk factor for infection. PMID- 1885735 TI - Production and characterization of monoclonal antibodies directed against the lipopolysaccharide of Francisella tularensis. AB - Two monoclonal antibodies (FT14 and FT2F11) directed against the lipopolysaccharide (LPS) of Francisella tularensis were produced for use in tests to detect the organism in environmental samples and clinical specimens. The specificity of the antibodies was determined by enzyme-linked immunosorbent assay (ELISA) and immunoblotting. Both antibodies detected LPS from F. tularensis by ELISA, but only one antibody, FT14, was serologically active in an immunoblot. Treatment of the LPS with detergents prior to ELISA eliminated its binding to FT2F11 but not FT14. Qualitatively, both antibodies detected 10 different strains of F. tularensis by ELISA, but quantitatively, FT14 gave a detectable reaction with 10(3) organisms, whereas FT2F11 was able to detect only 10(5) organisms. FT14 did not cross-react with LPS from a range of other gram-negative species of bacteria, whereas FT2F11 cross-reacted against Vibrio cholerae LPS. Neither antibody showed cross-reactions when entire gram-negative organisms were used as antigens. In a competition ELISA, the two monoclonal antibodies were shown to compete for different epitopes. FT14 was strongly inhibited by purified O side chain from F. tularensis LPS, but FT2F11 was only weakly inhibited. It was inferred from those results that FT14 is directed against the O side chain and that FT2F11 is directed against the core. PMID- 1885736 TI - Immunologic function in a cohort of human immunodeficiency virus type 1 seropositive and -negative healthy homosexual men. AB - The study objectives were to determine the early effects of human immunodeficiency virus type 1 (HIV-1) infection on both phenotypic and functional immunologic markers in healthy homosexual men, to ascertain the relationships of these markers to each other, and to discover which markers were affected by enrollment in an AIDS study in which HIV-1 serostatus would be determined. The major findings were as follows. (i) The CD4/CD8 ratio and lymphocyte proliferative response to pokeweed mitogen were the characteristics most affected by early HIV-1 infection. (ii) The loss in CD4 cells observed in the HIV-1 positive homosexual men was entirely due to diminished numbers of the memory subset. CD4+ CD29+. The reciprocal subset of CD4, CD4+ CD45RA+, did not differ in the two groups of homosexual men at either time point or in the controls. (iii) Prior to learning their HIV-1 serostatus, HIV-1 antibody-negative risk-group males had lower phytohemagglutinin (PHA) responses than the controls did. In the assays following notification of their seronegativity, however, these men had PHA values which were not different from those of the controls. In the HIV-1-positive group, the responses to both PHA and pokeweed mitogen were below those of both HIV-1-negative groups and did not change after serostatus notification. (iv) The activity of natural killer cells was lower in the risk-group men than in the controls at both pre- and postdiagnosis but was not related to HIV-1 serostatus. (v) In this cohort of homosexual men, the CD4/CD8 ratio correlated significantly with the functional measures of immunologic status in the HIV-1-positive men, but not in the HIV-1-negative men. PMID- 1885737 TI - Comparison of the autoSCAN-W/A rapid bacterial identification system and the Vitek AutoMicrobic system for identification of gram-negative bacilli. AB - The autoSCAN-W/A (W/A; Baxter MicroScan, West Sacramento, Calif.) with the new fluorometric Rapid Neg Combo 1 (RNC) panel is a fully automated fluorometric system for identification of both enteric and nonenteric gram-negative bacilli within 2 h. We compared the W/A with the Vitek AutoMicrobic System (Vitek AMS; Vitek Systems, Inc., Hazelwood, Mo.) for identification of 383 clinical isolates of gram-negative bacilli. The API 20E (Analytab Products, Plainview, N.Y.) and conventional biochemical testing were used as the reference systems. The W/A correctly identified 336 isolates (87.7%) to the species level and classified an additional 29 isolates (7.6%) as correct with low probability (overall identification = 95.3%); the Vitek AMS correctly identified 355 isolates (92.7%) to the species level and classified an additional 8 isolates (2.1%) as correct with low probability (overall identification = 94.8%). A common set of 134 isolates of gram-negative bacilli was tested in both participating laboratories as a means of assessing interlaboratory agreement with both the W/A and the Vitek AMS. The overall agreements between the two laboratories were 86% with the W/A and 92% with the Vitek AMS. The W/A performed comparably to the Vitek AMS for identification of most gram-negative bacilli, actually exceeding the Vitek AMS for identification of nonenteric bacilli. Rapid time to identification and a high level of automation make the W/A an attractive system for clinical microbiology laboratories. PMID- 1885738 TI - Immunoblot analysis of the humoral immune response to Leishmania donovani infantum polypeptides in human visceral leishmaniasis. AB - Using the immunoblot technique, we have compared the reactions of Leishmania donovani infantum polypeptides with the immunoglobulin G of human sera from patients with parasitologically proven L. d. infantum infection, with suspected visceral leishmaniasis, and with other leishmaniases, protozoiases, helminthiases, and fungal or bacterial diseases. A 94-kDa component reacted with all L. d. infantum-infected sera and with 75% of sera from patients with clinical and serological but no parasitological diagnoses. No reaction was observed with sera from patients in the other disease groups or with control sera. Studies of eight different isolates, subspecies, and species of the genus Leishmania demonstrated that the 94-kDa component was expressed in all strains examined. PMID- 1885739 TI - False-positive Chlamydiazyme results during urine sediment analysis due to bacterial urinary tract infections. AB - Our study examined whether urinary tract infections (UTIs) would cause false positive results when urine sediment was tested with the Chlamydiazyme (CZ) system. Thirty-six infected urine samples and fifteen controls were studied. All controls were negative. Forty-seven percent of Escherichia coli UTIs (n = 30) and 100% of Klebsiella pneumoniae UTIs (n = 4) were positive on CZ testing of urine sediment. Nine E. coli UTIs positive by CZ were negative by direct fluorescent antibody staining. When suspensions of the pure cultures were analyzed, 47% of E. coli and 100% of K. pneumoniae samples were CZ positive. False-positive results were not related to organism biotype or urine characteristics, including pH, specific gravity, and leukocyte count. We conclude that the presence of a UTI and also bacterial contamination must be ruled out prior to urine sediment testing. PMID- 1885740 TI - Effect of Tween 80 on formation of the superficial L1 layer of the Mycobacterium avium-Mycobacterium intracellulare complex. AB - The effects of Tween 80 supplementation of liquid culture medium on the formation of the superficial L1 layer of the Mycobacterium avium-Mycobacterium intracellulare complex (MAC) were examined by serological and scanning electron microscopic experiments. Specific antiserum to the glycopeptidolipids on the L1 layer of M. avium S-139, made in a rabbit, was used for seroagglutination reactions with antigens prepared from strain S-139 grown in medium supplemented with various levels of Tween 80 (0, 0.05, 0.5, 5, and 50 mg/ml). The agglutination titers gradually decreased as the concentration of Tween 80 rose. Scanning electron microscopy showed that the fibrillar materials consisting mainly of glycopeptidolipids on the L1 layer of strain S-139 also disappeared with increases in the concentration of Tween 80. In addition, there was no obvious correlation between (i) the plasmid DNAs and serotypes of MAC and (ii) formation of the L1 layer of MAC. It is therefore concluded that Tween 80 used to supplement liquid culture medium affects formation of the L1 layer, which has been considered to be one of the pathogenic factors of MAC. PMID- 1885741 TI - Enzyme immunoassay for detection of antibodies against eastern equine encephalomyelitis virus in sentinel chickens. AB - We developed an enzyme immunoassay (EIA) for the detection of immunoglobulin M (IgM) and IgG subclass antibodies directed against eastern equine encephalomyelitis (EEE) virus in chickens. The assays were compared with the serum plaque reduction neutralization test (PRNT) and the hemagglutination inhibition (HI) test for ability to detect antibodies against EEE virus in laboratory-infected birds. No cross-reactivity was detected in serum from chickens inoculated with St. Louis encephalitis or Highlands J virus. The interval after infection when EEE virus-specific antibodies were first detected by IgM and IgG EIAs was found to be similar to that determined by the PRNT and HI tests: 2 to 4 days. The IgG EIA, PRNT, and HI test detected antibodies to EEE virus for at least 27 to 30 days after inoculation. In contrast, serum from five of seven chickens did not contain detectable IgM 30 days after infection. Similarly, in all three naturally infected sentinel chickens from Maryland, IgM class antibody was undetectable 1 to 5 weeks after IgM was initially detected. EIAs provide simple and rapid alternatives to traditional tests for monitoring EEE virus infections in sentinel chicken flocks. Moreover, the IgM EIA provides a means to separate recently infected chickens from those infected greater than or equal to 1 month earlier. PMID- 1885743 TI - Evaluation of monoclonal antibody-based capture enzyme immunoassays for detection of specific antibodies to measles virus. AB - Monoclonal antibodies to the hemagglutinin protein, fusion protein, phosphoprotein, matrix protein, and nucleoprotein of measles virus were evaluated as detector antibodies in capture enzyme immunoassays (EIAs) for the detection of specific serum immunoglobulin G (IgG), IgA, and IgM antibodies to measles virus. A pool of monoclonal antibodies to hemagglutinin protein and nucleoprotein proved optimal and was further evaluated. Specific IgM was detected in 97% of adolescents with clinical measles, 97% of infants 3 weeks postvaccination, and less than 1% of normal serum specimens. Specific IgA antibodies were found in 97% of adolescents with clinical measles, 97% of infants 3 weeks postvaccination, and less than 1% of normal serum specimens. Specific IgA antibodies were found in 97% of clinical measles cases and vaccinees, in 26% of healthy persons, and in 36% of infants 8 months postvaccination; consequently, IgA antibodies were not a useful indicator of recent measles infection. A significant increase in IgG antibodies between paired specimens was detected in 92% of clinical cases and all vaccinees. Only 59% of infant specimens had persistent IgG antibodies as detected by capture EIA at 8 months postvaccination, whereas all specimens had antibodies as detected by hemagglutination inhibition and plaque neutralization. An alternative indirect EIA, in which antigen was directly absorbed to the solid phase, was more sensitive than the capture design, detecting IgG antibodies in all infants postvaccination. When standardized with a microneutralization assay for the detection of persistent antibodies, the indirect IgG EIA gave predictive values for positive and negative tests exceeding 90%. Our capture IgM and indirect IgG EIAs provide a practical combination of serologic tests for the determination of acute measles virus infection and past exposure to measles virus or vaccine, respectively. PMID- 1885742 TI - Effects of incubation time and temperature on microbiologic sampling procedures for hemodialysis fluids. AB - To prevent pyrogenic reactions and bacteremia in hemodialysis patients, the Association for the Advancement of Medical Instrumentation and the Centers for Disease Control recommend culturing of hemodialysis fluids (water and dialysate) at least once a month. The recommendations for total microbial counts are (i) less than or equal to 200 CFU/ml in water used to prepare dialysate or reprocess hemodialyzers and (ii) less than or equal to 2,000 CFU/ml for the dialysate. In accordance with the Association for the Advancement of Medical Instrumentation recommendations all cultures should be incubated at 37 degrees C for 48 h on suitable culture media, such as Trypticase soy agar, standard methods agar, or one of several commercially available assay systems. There have been suggestions that lower temperatures and longer incubation might improve the recovery of bacteria from water and dialysate. In this study bacterial recovery from various dialysis fluids (water, bicarbonate dialysate, and bicarbonate concentrate) at 30 and 37 degrees C was compared. Duplicate sets of samples were membrane filtered (pore size, 0.45 microns); one set was incubated at 30 degrees C and the other was incubated at 37 degrees C for 72 h. The number of visible colonies was counted every 24 h by using a dissecting microscope. No significant difference was observed in specimens incubated at 37 degrees C for 48 h compared with those incubated at 30 degrees C for 72 h. Also, bacterial recovery was significantly better when samples of bicarbonate dialysate or bicarbonate concentrate were plated on Trypticase soy agar as opposed to standard methods agar. PMID- 1885745 TI - Localization of endogenous activity of phospholipases A and C in Ureaplasma urealyticum. AB - Endogenous activities of phospholipases A and C in Ureaplasma urealyticum were assayed in cellular fractions of exponential-phase cells. Enzymatic studies indicated that ATPase activity was localized in the plasma membrane fraction and NADH and NADPH dehydrogenase activities were localized in the cytosol fraction. Studies with purified ureaplasma membranes demonstrated that, of three serovars tested, endogenous phospholipase A1, A2, and C activities were localized in the plasma membrane. Very low levels of activity were observed in the cytosol fractions. Phospholipase A2 activity in the plasma membrane was 3- to 5-fold higher than the activity in the lysates and 60- to 300-fold higher than the activity of phospholipase A1. Phospholipase C was localized mainly in the plasma membrane, with 20% found in the cytosol fraction. The levels of activity were comparable among the three serovars. There was a significantly lower level of activity in cells from the stationary growth phase than in the exponential phase. Significant differences were observed in the phospholipase A activities among the U. urealyticum serovars 3, 4, and 8. Phospholipase A2 activity was twofold higher in serovar 8 membranes, and phospholipase A1 activity was twofold higher in serovar 3 membranes. These results demonstrate that endogenous activities of phospholipase A and C are localized primarily in the plasma membrane fraction of U. urealyticum. The specific activities in the membranes of the phospholipases varied among the three serovars. Phospholipase enzymes may function as virulence factors in U. urealyticum and may vary among the serovars. PMID- 1885744 TI - Trabulsiella guamensis, a new genus and species of the family Enterobacteriaceae that resembles Salmonella subgroups 4 and 5. AB - In 1985 the vernacular name Enteric Group 90 was coined for a small group of strains that had been referred to our laboratory as probable strains of Salmonella but did not agglutinate in Salmonella typing antisera. By DNA-DNA hybridization (hydroxyapatite method, 32P), seven strains of Enteric Group 90 were found to be closely related (98 to 100% at 60 degrees C and 94 to 100% at 75 degrees C) to the first strain received (0370-85). The relatedness of Enteric Group 90 to 62 strains of other species of the family Enterobacteriaceae was only 6 to 41%, with the highest values obtained with strains of Salmonella, Kluyvera, Shigella, Klebsiella, Enterobacter, and Citrobacter. We propose a new genus, Trabulsiella, with a single new species, Trabulsiella guamensis, for the highly related group of eight strains formerly known as Enteric Group 90. The type strain is designated ATCC 49490 (CDC 0370-85). T. guamensis strains grew well at 36 degrees C and had positive reactions in the following tests: methyl red, citrate utilization (Simmons) (38% positive at day 1, 88% positive at 2 days), H2S production, lysine decarboxylase, arginine dihydrolase (50% positive at 2 days, 100% positive at 7 days), ornithine decarboxylase, motility, growth in KCN medium, mucate fermentation, acetate utilization, nitrate reduction to nitrite, weak tyrosine hydrolysis (88% positive at 2 days, 100% positive at 7 days), and ONPG (o-nitrophenyl-beta-D-galactopyranoside) test. The strains fermented D glucose with gas production and fermented L-arabinose, cellobiose, D-galactose, D galacturonate, maltose, D-mannitol, D-mannose, L-rhamnose, D-sorbitol, trehalose, and D-xylose. T. guamensis strains had negative reactions in the following tests: indole production (13% positive), Voges-Proskauer, urea hydrolysis, phenylalanine deaminase, malonate utilization, lipase (corn oil), DNase, oxidase, pigment production, and acid production from adonitol, D-arabitol, dulcitol, erythritol, myo-inositol, melibiose, alpha-methyl-D-glucoside, raffinose, and sucrose. There were delayed positive reactions for gelatin liquefaction (22 degrees C), which was positive at 12 to 23 days, esculin hydrolysis (13% positive at day 1, 50% positive at 7 days), lactose fermentation (13% positive at 3 to 7 days, 100% positive at 8 to 10 days), glycerol fermentation (88% positive at 7 days), and salicin fermentation (13% positive at day 1, 88% positive at 7 days). All strains were susceptible by the disk diffusion method to colistin, nalidixic acid, gentamicin, streptomycin, kanamycin, chloramphenicol, and trimethoprim sulfamethoxazole, and most strains were susceptible to sulfadiazine (75% susceptible), tetracycline (88%), and carbenicillin (75%). The strains were resistant to penicillin, cephalothin, and ampicillin. The strains were isolated from vacuum cleaner dust (five strains), soil (one strain), and human feces (two strains). Although T. guamensis can occur in human diarrheal stools, there is no evidence that it actually causes diarrhea. Its main interest to clinical microbiologists may be its possible misidentification as a strain Salmonella. PMID- 1885746 TI - Detection of tetanus antitoxin using Eu(3+)-labeled anti-human immunoglobulin G monoclonal antibodies in a time-resolved fluorescence immunoassay. AB - Tetanus antitoxin in human sera was detected with solid-phase immunoassays in microtitration modules coated with tetanus toxoid by using Eu(3+)-labeled anti human monoclonal antibodies on the basis of an exactly calibrated antibody standard. The use of a time-resolved fluorescence immunoassay (TR-FIA) significantly improved the quantitative detection of tetanus antitoxin over that of the enzyme-linked immunosorbent assay (ELISA) technique because of its high sensitivity and its wide measurement range, detecting antibody levels between 0.001 and 12.5 IU/ml with a single serum dilution of 1:100. For the same purpose, two different serum dilutions (1:100 and 1:1,000) were needed in the ELISA technique. TR-FIA is reproducible and can be performed in 3.5 h. A study of 2,630 serum samples was undertaken to examine the age-dependent distribution of titer levels, indicating the decline of sufficient protection in patients older than 60 years. The wide measurement range of TR-FIA enabled fast examination of large numbers of serum samples without the need for repetition, with further sample dilution, as was often necessary in the ELISA procedure. PMID- 1885747 TI - Optimization of a rapid nonisotopic DNA probe assay for Plasmodium falciparum in the Gambia. AB - An enzyme-linked synthetic DNA probe which hybridizes to repetitive DNA of Plasmodium falciparum was used in conjunction with a microtiter-based lysis and filtration blood processing procedure. An assay protocol was developed that is more sensitive and robust than previous protocols, which use stored blood and phenol extraction. In comparison with thick smear examination, 33% positive, 60% negative, and 7% conflicting scores were recorded from 390 analyzed clinical samples, and the sensitivity threshold was about 30 parasites per mm3 of blood. PMID- 1885748 TI - Spotted fever group rickettsiae or Borrelia burgdorferi in Ixodes cookei (Ixodidae) in Connecticut. AB - Immatures and females of Ixodes cookei, a hard-bodied tick, were collected from woodchucks and other mammals in the northeastern United States and examined for spotted fever group rickettsiae and Borrelia burgdorferi. Of the 93 nymphs analyzed by a hemolymph test, 4 (4.3%) harbored rickettsiae. Six (15%) of 40 females were also infected. All infected ticks were collected from woodchucks in Connecticut. Indirect fluorescent antibody staining of midgut tissues from 128 nymphs revealed B. burgdorferi in two (1.6%) ticks, whereas larval and female ticks were negative. Further consideration should be given to I. cookei as a possible vector of spotted fever group rickettsiae or spirochetes that cause Lyme borreliosis. PMID- 1885749 TI - Detection of the Lyme disease bacterium, Borrelia burgdorferi, by using the polymerase chain reaction and a nonradioisotopic gene probe. AB - A 419-bp region of the flagellin gene sequence of Borrelia burgdorferi was used as a target for the polymerase chain reaction. With a nonradioactively labeled gene-specific probe, sensitivity to as few as 1 to 10 spirochetes was observed. The targeted gene fragment was conserved in the American and European strains of B. burgdorferi tested and among several other pathogenic borreliae. PMID- 1885750 TI - Cross-reactive antibodies induced by a monovalent influenza B virus vaccine. AB - Influenza viruses related to the markedly antigenically divergent strains B/Yamagata/16/88 and B/Victoria/2/87 are circulating in human populations. Adults develop cross-reacting antibodies against recent and earlier influenza B virus strains after vaccination with B/Yamagata/16/88, probably because of previous influenza B virus infections or immunizations. Vaccines containing B/Yamagata/16/88 should adequately protect adults against B/Victoria/2/87 infections. PMID- 1885751 TI - Evaluation of a rapid screening test for detecting group B streptococci in pregnant women. AB - The QUIDEL Group B Strep Test is an enzyme immunoassay (EIA) that was compared with culture for the rapid detection of moderate to high levels of group B streptococci (GBS) colonization in pregnant women. A total of 331 pregnant women were included in the study protocol, and GBS were cultured from 19 of these patients in moderate or greater amounts (incidence of 5.7%). Compared with culture, the EIA had a sensitivity, specificity, and positive and negative predictive values of 89, 99, 89, and 99%, respectively. With a sensitivity of 89%, the 95% confidence interval for this assay is 88 to 90%. The QUIDEL EIA test can be performed in less than 10 min and appears to be a reliable method for detecting moderate or greater amounts of GBS in vaginal or cervical specimens. PMID- 1885752 TI - Chlamydia pneumoniae elementary body antigenic reactivity with fluorescent antibody is destroyed by methanol. AB - Methanol, used for fixing chlamydia organisms to microscopic slides, was shown to eliminate the antigenic reactivity of Chlamydia pneumoniae elementary bodies with fluorescent antibodies. Acetone fixation had no adverse effect. Chlamydia trachomatis and Chlamydia psittaci were not affected by methanol fixation. The effect of methanol on C. pneumoniae is another characteristic that differentiates this species from the other two chlamydia species. PMID- 1885753 TI - Detection of Anaplasma marginale rickettsemia prior to onset of clinical signs by using an antigen capture enzyme-linked immunosorbent assay. AB - An antigen capture enzyme-linked immunosorbent assay was developed by using monoclonal antibodies to conserved epitopes on the Anaplasma marginale MSP1a surface protein. The assay sensitivity was 1.1 (+/- 0.5)% parasitized erythrocytes, and all infected cattle were detected prior to development of 2.0% parasitized erythrocytes. Positive tests preceded the onset of anemia by a mean of 2 days. The assay was specific for anaplasmosis, as demonstrated by nonreactivity with another common hemoparasitic pathogens. PMID- 1885754 TI - Effect of heat or formalin treatment of leptospires on antibody response detected by immunoblotting. AB - Leptospira interrogans serovar icterohaemorrhagiae RGA (RGA), live or heated at 56 degrees C for 15 min or treated with Formalin, was injected into rabbits to prepare hyperimmune serum. The pathogens L. interrogans serovars icterohaemorrhagiae RGA, icterohaemorrhagiae 1, canicola Moulton, grippotyphosa Andaman, hardjo Hardjoprajitno, and pomona Pomona and the nonpathogen Leptospina biflexa serovar patoc Patoc 1 were processed for sodium dodecyl sulfate polyacrylamide gel electrophoresis, and after electrophoresis they were then transferred to nitrocellulose paper. Antiserum against RGA (live, heat killed, or Formalin killed) was used on one of each of the three blots. Formalin appeared to completely eliminate antibody response to antigens with the molecular weight of 14,000 to 20,000 (14K to 20K) but did expose an antigen at approximately 23K in the pathogens only. This same band had only slight reactivity when antiserum against heat-killed RGA was used. Heating also eliminated cross-reactivity in the 19K to 30K range and partially degraded bands in the 14K to 20K region so that one broad band rather than several discrete bands appeared. The three antiserum specimens cross-reacted with all of the serovars tested, but fewer antigens of grippotyphosa and hardjo reacted with the antisera. Against patoc, reactivity was limited primarily to the flagellar region. The most cross-reactivity was with the antiserum prepared by using live leptospires. PMID- 1885756 TI - The Year 2000 National Health Objectives. PMID- 1885755 TI - Evaluation of the rapid CLEARVIEW Chlamydia test for direct detection of chlamydiae from cervical specimens. AB - The CLEARVIEW Chlamydia test (Unipath, Mountain View, Calif.), a 30-min immunoassay, was compared to a standard tissue culture technique for the direct detection of chlamydiae from 677 cervical specimens obtained from 667 patients. For data analysis, 15 specimens were eliminated because of toxicity in the culture and 14 were eliminated because of failure of the extracted specimen to migrate in the CLEARVIEW test, one of the latter group being culture positive. Of the remaining 648 specimens, 40 were culture positive, of which 38 were detected by the CLEARVIEW test, and 12 specimens were positive only by the CLEARVIEW test. Therefore, the CLEARVIEW in comparison with culture was easier to perform, more rapid, and in this low prevalence (6.2%) population had a 95.0% sensitivity, 98.0% specificity, and 76.0% positive and 99.7% negative predictive values. PMID- 1885758 TI - The role of community-based organizations in responding to the AIDS epidemic: examples from the HRSA service demonstrations. AB - This paper considers the role of community-based organizations in providing out of-hospital services to persons with AIDS, using information collected as part of a case-study evaluation of AIDS service demonstration grants in four cities. Community-based organizations which existed prior to the AIDS epidemic have been reluctant to expand services to persons with AIDS. The widest array of services is provided by new broad-based organizations. Also, exclusive reliance on community-based organizations for service delivery leads to inequities in the delivery system, due to difficulties in developing such organizations in low income communities. PMID- 1885759 TI - Science, advocacy and health policy: lessons from the New Zealand tobacco wars. AB - The New Zealand Smoke-Free Environments Act was passed in August 1990 and is a central component of a comprehensive tobacco control policy. The passage of the Act was preceded by a long campaign. The essential components of this campaign were: international scientific evidence and the estimates of tobacco-caused mortality in New Zealand; activists groups supported by established health charities and the health professions; a sympathetic Health Department bureaucracy; a committed and powerful Minister of Health; and a relatively weak industry. The legislation passed despite adverse timing, the absence of bipartisan political support, and the pressure of industry-supported sports lobby groups. The campaign provides a model for other health issues in New Zealand and lessons for the tobacco wars elsewhere. PMID- 1885757 TI - Health promotion versus health protection? Employees' perceptions and concerns. AB - The "second public health revolution" targets factors in the environment, together with lifestyle, to prevent illness and untimely death. Yet the growth of the "wellness movement" has driven a wedge between public health advocates who argue for environmental solutions and those whose major focus is individual behavior. This tension is nowhere more evident than in the workplace, where the new wellness professionals are at odds with specialists in occupational health and industrial hygiene. This paper reports findings from a cross-sectional survey of a sizeable sample of workers at six New England facilities of a very large American manufacturing firm, assessing their perceptions of risk in the two domains: environmental exposures and lifestyle risks. Multiple regression analyses reveal that both job risks and life risks are associated with a variety of potentially costly and disruptive health problems, even after controlling for demographic and occupational factors. This analysis suggests that wellness programs in the workplace will be more effective if they integrate environmental protection with efforts to reduce lifestyle risk. PMID- 1885760 TI - Regional perinatal care in crisis: a case study of an urban public hospital. AB - Regionalized perinatal care is intended to guarantee pregnant women and neonates access to appropriate care regardless of ability to pay. Its effectiveness depends on the willingness of hospitals to transfer high-risk patients according to established protocols and affiliations. This study examines maternal transfers (n = 896) to Cook County Hospital (CCH), a public facility and a designated perinatal center in Chicago. In 1987 and 1988, the majority (68%) of maternal transfers to CCH came from out-of-network hospitals, and 52% of these came directly from another perinatal center. The data indicate that 62% of the out-of network transfers who delivered were medically high-risk. The study also documents the transfer of women in active labor, a violation of federal law. The term "perinatal dumping" is introduced to mean the transfer of high-risk pregnant women between hospitals for economic rather than medical reasons. Strategies for safeguarding the integrity of regionalized perinatal care are discussed. PMID- 1885761 TI - Capitation in dentistry: original concepts and current reality. AB - Modern dental capitation was conceived as being based on staff model group practice, receiving regular periodic payments to provide comprehensive care with few exclusions, limitations and copayments, to a given population. High utilization, completion and recall rates were expected. Examples are presented. The dominant form of capitation has become a network of solo and small group practices, usually with a for-profit intermediary. Premiums are low and administrative costs are high. There are many exclusions and limitations. Low utilization and under-treatment are endemic. Specific examples are presented. The reasons for this development include competition among dentists concerned about busyness, and predominance of cost control concerns over quality concerns on the part of purchasers. PMID- 1885762 TI - Comparative policies of two national dental associations: Norway and the United States. AB - The major issues and challenges confronting the dental professions in the United States and Norway were studied through speeches of and interviews with the presidents of the American Dental Association (ADA) and the Norwegian Dental Association (NDA) in the period 1980-86. The issues most frequently dealt with related to public authorities, particularly legislation and government involvement in dental practice. Anxiety concerning "busyness," the future dental market, and a drop in the quality of applicants to dental schools were also major subjects. The spokespersons of both associations were engaged in increasing the demand for dental services by marketing, but they were ambivalent regarding advertising, especially individual advertising. Both were concerned with protecting dentistry's autonomy. While the Norwegian presidents apparently feared the medical profession's influence upon dentistry, the Americans were concerned with the hygienists and denturists, and with the insurance companies which they suspected of intruding into the dentist-patient relationship. The presidents' statements, which frequently varied, were apparently influenced by the current domestic political climate, the basic socio-political principles of the two countries, and the different socio-demographic make-up of their memberships. PMID- 1885763 TI - MUC-2 human small intestinal mucin gene structure. Repeated arrays and polymorphism. AB - MUC-2, the first described intestinal mucin gene, has become important as a prototype for secreted mucins in several organ systems. However, little is known about its protein backbone structure and hence its role in diseases such as colon cancer, ulcerative colitis, and cystic fibrosis, which are known to have mucin abnormalities. Studies in this manuscript show that MUC-2 contains two distinct regions with a high degree of internal homology, but the two regions bear no significant homology to each other. Region 1 consists mostly of 48-bp repeats which are interrupted in places by 21-24-bp segments. Several of these interrupting sequences show similarity to each other, creating larger composite repeat units. Region 1 has no length polymorphisms. Region 2 is composed of 69-bp tandem repeats arranged in an uninterrupted array of up to 115 individual units. Southern analysis of genomic DNA samples using TaqI and HinfI reveals both length and sequence polymorphisms which occur within region 2. The sequence polymorphisms have different ethnic distributions, while the length polymorphisms are due to variable numbers of tandem repeats. PMID- 1885764 TI - Maple syrup urine disease in Mennonites. Evidence that the Y393N mutation in E1 alpha impedes assembly of the E1 component of branched-chain alpha-keto acid dehydrogenase complex. AB - Maple Syrup Urine Disease (MSUD) in Mennonites is associated with homozygosity for a T to A transversion in the E1 alpha gene of the branched-chain alpha-keto acid dehydrogenase complex. This causes a tyrosine to asparagine substitution at position 393 (Y393N). To assess the functional significance of this missense mutation, we have carried out transfection studies using E1 alpha-deficient MSUD lymphoblasts (Lo) as a host. The level of E1 beta subunit is also greatly reduced in Lo cells. Efficient episomal expression in lymphoblasts was achieved using the EBO vector. The inserts employed were chimeric bovine-human cDNAs which encode mitochondrial import competent E1 alpha subunit precursors. Transfection with normal E1 alpha cDNA into Lo cells restored decarboxylation activity of intact cells. Western blotting showed that both E1 alpha and E1 beta subunits were markedly increased. Introduction of Y393N mutant E1 alpha cDNA failed to produce any measurable decarboxylation activity. Mutant E1 alpha subunit was expressed at a normal level, however, the E1 beta subunit was undetectable. These results provide the first evidence that Y393N mutation is the cause of MSUD. Moreover, this mutation impedes the assembly of E1 alpha with E1 beta into a stable alpha 2 beta 2 structure, resulting in the degradation of the free E1 beta subunit. PMID- 1885765 TI - Targeted and highly efficient gene transfer into CD4+ cells by a recombinant human immunodeficiency virus retroviral vector. AB - We have established a recombinant HIV gene transfer system based on transient expression of the HIV packaging functions and a recombinant vector genome in monkey kidney Cos cells. The recombinant HIV retroviral vector introduced the neoR gene into CD4+ cells with high efficiency, comparable to that achieved with the highest titer amphotropic murine recombinant retrovirus. Vector preparations were devoid of replication competent, infectious HIV. Gene transfer was dependent on CD4 expression, as shown by expression of the CD4 gene in HeLa cells, and could be inhibited by soluble CD4. This specific and efficient gene transfer system may be useful for development of gene therapy for which T cells are the desired targets. PMID- 1885766 TI - Endobronchial allergen challenge in asthma. Demonstration of cellular source of granulocyte macrophage colony-stimulating factor by in situ hybridization. AB - Airway inflammation is thought to play an important role in the pathogenesis of asthma. We have used in situ hybridization and an immunoassay to determine whether granulocyte macrophage colony-stimulating factor (GM-CSF) (a cytokine capable of eosinophil activation) is present in the airway of asthmatics (n = 6) who have 37.0 +/- 15.1% airway eosinophilia after endobronchial allergen challenge. Levels of immunoreactive GM-CSF (less than 4 pg/ml pre-allergen versus 180.5 +/- 46.9 pg/ml post-allergen) increased significantly 24 h after endobronchial allergen stimulation. The cellular source of bronchoalveolar lavage (BAL) GM-CSF, as determined by in situ hybridization and immunoperoxidase staining, was derived predominantly from UCHL-1 positive BAL lymphocytes, as well as from a smaller population of alveolar macrophages. Before local endobronchial allergen challenge, less than 1% of lymphocytes and alveolar macrophages recovered by BAL expressed GM-CSF mRNA, whereas after allergen stimulation 92.6 +/- 3.4% of lymphocytes and 17.5 +/- 22.7% of alveolar macrophages expressed GM CSF mRNA. This study provides evidence that in an experimental model of allergen induced asthma, activation of the immune and inflammatory response (BAL lymphocyte and alveolar macrophage production of GM-CSF) is temporally associated with an inflammatory cell influx of eosinophils into the airway. PMID- 1885767 TI - Hypoxia induces endothelin gene expression and secretion in cultured human endothelium. AB - Hypoxia in vivo is associated with constriction of the distal vasculature in the lung. Uniquely situated at the interface between blood and the vessel wall proper, the vascular endothelium may release vasoactive mediators in the setting of hypoxia. Endothelin-1 is a potent vasoconstrictor released by endothelial cells that could function as a paracrine regulator of vascular tone. We found that physiologic low oxygen tension (PO2 = 30 Torr) increased endothelin secretion from cultured human endothelial cells four to eightfold above the secretion rate at ambient oxygen tension. This increase in secretion was accompanied by a corresponding increase in the transcriptional rate of the preproendothelin gene resulting in increased steady-state mRNA levels of preproendothelin. In contrast, the transcription of a number of other growth factor-encoding genes, including transforming growth factor-beta, was unaffected by hypoxia. Endothelin transcript production increased within 1 h of hypoxia and persisted for at least 48 h. In addition, the stimulatory effects of low oxygen tension on endothelin mRNA levels were reversible upon reexposure to 21% oxygen environments. These findings suggest a role for endothelin in the control of regional blood flow in the vasculature in response to changes in oxygen tension. PMID- 1885768 TI - Mechanisms of viral pathogenesis. Distinct forms of reoviruses and their roles during replication in cells and host. PMID- 1885770 TI - Niemann-Pick type B disease. Identification of a single codon deletion in the acid sphingomyelinase gene and genotype/phenotype correlations in type A and B patients. AB - Types A and B Niemann-Pick disease both result from the deficient activity of the lysosomal hydrolase, acid sphingomyelinase (E.C. 3.1.4.12). Type A Niemann-Pick disease is a severe neurodegenerative disorder of infancy which leads to death by three years of age, whereas Type B disease has a later age at onset, little or no neurologic involvement, and most patients survive into adulthood. To investigate the molecular basis for the remarkable phenotypic heterogeneity, the nature of the mutations causing Type B Niemann-Pick disease in Ashkenazi Jewish patients was determined. The entire acid sphingomyelinase coding region from an Ashkenazi Jewish Type B patient was polymerase chain reaction-amplified, subcloned, and completely sequenced. A three-base deletion was identified of nucleotides 1821 1823 in the cDNA which predicted the removal of an arginine residue from position 608 of the acid sphingomyelinase polypeptide (delta R608). The other cDNA clones from this patient had the R496L mutation previously identified in Type A Niemann Pick disease patients. Both Ashkenazi Jewish Type B patients were heteroallelic for the delta R608 mutation, whereas this allele was not present in 15 unrelated non-Jewish Type B patients, with the notable exception of one mildly affected patient of Arabic descent who was homoallelic for the delta R608 mutation. These results indicate that the delta R608 mutation predicts the Type B Niemann-Pick disease phenotype, even in the presence of the R496L Type A allele, thereby providing the first genotype/phenotype correlation for this lysosomal storage disease. Although only two patients have been studied, it appears that the delta R608 mutation occurs frequently in Type B Niemann-Pick disease patients of Ashkenazi Jewish descent. PMID- 1885769 TI - Nonsense mutations affect C1 inhibitor messenger RNA levels in patients with type I hereditary angioneurotic edema. AB - Members of two unrelated families with type I hereditary angioneurotic edema (HANE) were found to have elevated levels of C1 inhibitor (C1INH) mRNA. DNA sequence analysis of PCR-amplified monocyte C1INH mRNA revealed normal and mutant transcripts, as expected in this disorder that occurs in heterozygous individuals. Single base mutations near the 3' end of the coding sequence were identified in affected members of each family. One mutation consisted of insertion of an adenosine at position 1304 which created a premature termination codon (TAA), whereas the second consisted of deletion of the thymidine at position 1298 which created a premature termination codon (TGA) 23 nucleotides downstream. These mutations are approximately 250 nucleotides upstream of the natural termination codon. Nuclear run-off experiments in one kindred revealed no difference in transcription rates of the C1INH gene between the patients and normals. C1INH mRNA half-life experiments were not technically feasible because of the prolonged half-life of the normal transcript. Dideoxynucleotide primer extension experiments allowed the differentiation of the normal and mutant transcripts. These studies showed that the mutant transcript was not decreased relative to the normal, and this therefore was at least partially responsible for the C1INH mRNA elevation. This elevation may be due to the decreased catabolism of the mutant transcript. PMID- 1885771 TI - Differential processing of proenkephalin-A by human peripheral blood monocytes and T lymphocytes. AB - Human peripheral blood mononuclear cells are analyzed for preproenkephalin gene expression and peptide processing. Met-enkephalin immunoreactivity as detected with a specific antiserum is found in the cytoplasm of monocytes but not in T lymphocytes. Secretion of met-enkephalin was analyzed with an RIA that is specific for the met-enkephalin pentapeptide. Unfractionated PBMC spontaneously released 40 pg/ml met-enkephalin and this increased two- to fourfold after stimulation with PHA. Lower levels (less than 100 pg/ml) of met-enkephalin were detected in supernatants from purified T cells that were activated with PHA and IL-2. In contrast, stimulation of purified monocytes with LPS or PMA resulted in the release of up to 600 pg/ml of the processed peptide. To examine whether T cells can produce met-enkephalin precursor peptides, T cell conditioned media were treated with trypsin and carboxypeptidase-B, which is known to release met enkephalin from the propeptide. This increased levels of met-enkephalin to 400 pg/ml, indicating that lymphocytes secrete the propeptide but do not process it to met-enkephalin. The 1.4-kb preproenkephalin mRNA is detected in activated blood mononuclear cells and in purified monocytes and T cells. To determine whether monocytes or lymphocytes express met-enkephalin in vivo, lymphoid tissues were analyzed by immunohistochemistry. In human spleen tissue, positive cells were found in the red pulp but not in the follicles, which is also consistent with met-enkephalin expression in monocytes. In summary, these results show that human peripheral blood mononuclear cells express preproenkephalin mRNA and that monocytes, but not T cells, process the propeptide to metenkephalin. PMID- 1885772 TI - Human eosinophils express functional interleukin 2 receptors. AB - Because T cell-derived cytokines may affect the functioning of eosinophils, we have investigated the capacity of human eosinophils to respond to IL-2. IL-2 was a potent chemoattractant with ED50 of 10(-12) M with eosinophils from all normal and eosinophilic donors tested. The monoclonal antibodies anti-Tac and TU27 against p55 (Tac/CD25) and p75 receptor subunits, respectively, each inhibited IL 2-dependent eosinophil migration. The molar potency of IL-2 and the inhibitory activity of each of the above antibodies suggest that high affinity heterodimeric IL-2 receptor complexes mediated the migration responses of eosinophils to IL-2. Binding of monoclonal antibody against p75 was not detectable by flow cytometry, and high affinity binding sites for 125I-IL-2 were below the limits of quantitation on eosinophils from individuals with eosinophilia. Expression of p55 (Tac/CD25) by eosinophils, without requirement for in vitro activation, was demonstrable by flow cytometry, radioimmunoprecipitation, and Northern blotting for mRNA. Surface expression of p55 on eosinophils from normal or eosinophilic individuals increased during culture for 24-48 h with a biologic activity purified from stimulated U937 cells and to a lesser extent with granulocyte macrophage CSF or lymphocyte chemoattractant factor but not with nine other cytokines. These studies indicate that blood eosinophils respond to IL-2 and identify one mechanism whereby activation of T lymphocytes may influence the function of eosinophils. PMID- 1885773 TI - Carbachol- and elevated Ca(2+)-induced translocation of functionally active protein kinase C to the brush border of rabbit ileal Na+ absorbing cells. AB - Protein kinase C is involved in mediating the effects of elevated Ca2+ in ileal villus Na+ absorbing cells to inhibit NaCl absorption. The present studies were undertaken to understand the mechanism by which this occurs. The effects of carbachol and the calcium ionophore A23187, agents which elevate intracellular Ca2+ and inhibit NaCl absorption in ileal villus cells, were studied. Carbachol treatment of villus cells caused a rapid decrease in protein kinase C activity in cytosol, with an accompanying increase in microvillus membrane C kinase. Exposure of the villus cells to calcium ionophore also caused a quantitatively similar decrease in cytosol C kinase and increase in C kinase activity in the microvillus membrane. This increase caused by carbachol and Ca2+ ionophore was specific for the microvillus membrane. In fact, 30 s and 10 min after exposure of the cells to carbachol, basolateral membrane protein kinase C decreased, in a time-dependent manner; whereas 10 min of Ca2+ ionophore exposure did not alter basolateral C kinase. Exposure of villus cells to Ca2+ ionophore or carbachol caused similar increases in microvillus membrane diacylglycerol content. As judged by the ability to inhibit Na+/H+ exchange measured in ileal villus cell brush border membrane vesicles, the protein kinase C which translocated to the microvillus membrane was functionally significant. Inhibition of Na+/H+ exchange required ATP and was reversed by the protein kinase C antagonist H-7. In conclusion, the effect of carbachol and Ca2+ ionophore in regulation of ileal NaCl absorption is associated with an increase in microvillus membrane diacylglycerol content and functionally active protein kinase C. The effects of both carbachol and Ca2+ ionophore are different on brush border and basolateral membrane distribution of protein kinase C. PMID- 1885775 TI - Efficacy of antilipopolysaccharide and anti-tumor necrosis factor monoclonal antibodies in a neutropenic rat model of Pseudomonas sepsis. AB - Monoclonal antibodies (MAb) directed against bacterial lipopolysaccharide (LPS) and tumor necrosis factor-alpha (TNF) provide partial protection in experimental models of septic shock. To determine if additional benefit accrues from a combination of anti-TNF and anti-LPS MAb in the treatment of septic shock, a neutropenic rat model was developed to study active infection with Pseudomonas aeruginosa 12.4.4. Animals were treated intravenously with an irrelevant MAb (group 1); anti-TNF MAb (group 2); MAb directed against P. aeruginosa 12.4.4 LPS (group 3); or a combination of anti-TNF and anti-LPS MAb (group 4). None of the control animals in group 1 survived the 7-d period of neutropenia (0/16). In contrast, the survival rate was 44% in group 2 (P less than 0.02); 37% in group 3 (P less than 0.05); and 75% in group 4 (P less than 0.0002). The combination of monoclonal antibodies provided greater protection than either MAb given alone (P less than 0.05). Serum TNF levels during infection were significantly greater in groups 1 and 3 (20.1 +/- 3.3 U, mean +/- SE) than in groups 2 and 4 (0.9 +/- 0.8 U, P less than 0.0001). These results indicate that a combination of monoclonal antibodies to LPS and TNF have additive benefit in experimental Pseudomonas aeruginosa sepsis. This immunotherapeutic approach may be of potential utility in the management of serious, gram-negative bacterial infection in neutropenic patients. PMID- 1885774 TI - Differential responses of the endothelial and epithelial barriers of the lung in sheep to Escherichia coli endotoxin. AB - Although intravenous Escherichia coli endotoxin has been used extensively in experimental studies to increase lung endothelial permeability, the effect of E. coli endotoxin on lung epithelial permeability has not been well studied. To examine this issue in sheep, bidirectional movement of protein across the lung epithelial barrier was studied by labeling the vascular space with 131I-albumin and by instilling 3 ml/kg of an isosmolar protein solution with 125I-albumin into the alveoli. E. coli endotoxin was administered according to one of three protocols: intravenous alone (5-500 micrograms/kg), intravenous (5 micrograms/kg) plus low-dose alveolar endotoxin (10 micrograms/kg), and high-dose alveolar endotoxin alone (50-100 micrograms/kg). Alveolar liquid clearance was estimated based on the concentration of the instilled native protein. Sheep were studied for either 4 or 24 h. Although intravenous E. coli endotoxin produced a marked increase in transvascular protein flux and interstitial pulmonary edema, there was no effect on the clearance of either the vascular (131I-albumin) or the alveolar (125I-albumin) protein tracer across the epithelial barrier. High-dose alveolar E. coli endotoxin caused a 10-fold increase in the number of leukocytes, particularly neutrophils, that accumulated in the air spaces. In spite of the marked chemotactic effect of alveolar endotoxin, there was no change in the permeability of the epithelial barrier to the vascular or alveolar protein tracers. Also, alveolar epithelial liquid clearance was normal. Morphologic studies confirmed that the alveolar epithelial barrier was not injured by either intravenous or alveolar E. coli endotoxin. Thus, the alveolar epithelium in sheep is significantly more resistant than the lung endothelium to the injurious effects of E. coli endotoxin. PMID- 1885776 TI - Rapid alteration in circulating free thyroxine modulates pituitary type II 5' deiodinase and basal thyrotropin secretion in the rat. AB - TSH secretion is decreased by both T4 and T3. This negative feedback control of TSH secretion has been correlated with an increase in pituitary nuclear T3 content, and it is not clear whether T4 exerts its effect directly on the thyrotroph or after its deiodination to T3. However, levels of the pituitary enzyme catalyzing T4 to T3 conversion, 5'D-II, are decreased in the presence of an increased amount of T4. Thus, it is unclear why the thyrotroph would have a mechanism for modulating the production of T3, if T3 is, in fact, the sole bioactive signal providing negative feedback inhibition. To examine this apparent paradox, we administered EMD 21388, a compound which inhibits the binding of T4 to transthyretin resulting in a rapid increase in circulating free T4 levels, to rats pretreated with radiolabeled T4 and T3. We observed increases in pituitary and liver T4 content of greater than 150%, without increases in the respective tissue T3 contents. The EMD 21388-treated rats also exhibited a 25% decrease in pituitary 5'D-II activity (103.8 +/- 15.8 fmol 125I released.mg protein-1.h-1, vs. control, 137.4 +/- 15.9, mean +/- SE), as did rats treated with sodium salicylate, another compound that inhibits T4-TTR binding (100.8 +/- 7.1). TSH levels significantly decreased 2 h after the administration of EMD 21388. These data demonstrate that despite a T4-mediated decrease in pituitary 5'D-II activity, an increase in T4 independently decreases TSH secretion. PMID- 1885777 TI - Expression of AT2 receptors in the developing rat fetus. AB - Angiotensin II is known primarily for its effects on blood pressure and electrolyte homeostasis, but recent studies suggest that angiotensin II may play a role in the regulation of cellular growth. This study was undertaken to identify the angiotensin II receptor subtypes expressed during fetal and neonatal development and to characterize their cellular localization. Using an in situ receptor binding assay on sagittal frozen sections of fetal and neonatal rats, bound 125I-[Sar1,Ile8]-angiotensin II was visualized by film and emulsion autoradiography. Bound radioligand was detected by E11 (embryonic day 11) and maximal binding occurred by E19-21. Radioligand binding remained unaltered 30 min after birth, whereas a noticeable and stable decrease was observed 12 h postparturition. The highly abundant angiotensin II receptors were shown to be AT2 by the marked reduction in radioligand binding achieved with PD123177 (10( 7)M), a specific AT2 receptor antagonist, whereas DuP 753 (10(-5)M), an AT1 receptor antagonist, had little effect. Emulsion autoradiography showed radioligand binding in the undifferentiated mesenchyme of the submucosal layers of the intestine and stomach, connective tissue and choroid surrounding the retina, subdermal mesenchyme adjacent to developing cartilage, diaphragm, and tongue. Residual AT2 receptors were found on the dorsal subdermal region of the tongue 72 h after birth. AT1 receptors were detected in the placenta at E13 and in the aorta, kidney, lung, liver, and adrenal gland at E19-21, consistent with an adult distribution. The transient expression of AT2 receptors in the mesenchyme of the fetus suggests a role of angiotensin II in fetal development. PMID- 1885778 TI - Modulation of glucose regulation and insulin secretion by circadian rhythmicity and sleep. AB - To define the roles of circadian rhythmicity (intrinsic effects of time of day independent of the sleep or wake condition) and sleep (intrinsic effects of the sleep condition, irrespective of the time of day) on the 24-h variation in glucose tolerance, eight normal men were studied during constant glucose infusion for a total of 53 h. The period of study included 8 h of nocturnal sleep, 28 h of continuous wakefulness, and 8 h of daytime sleep. Blood samples for the measurement of glucose, insulin, C-peptide, cortisol, and growth hormone were collected at 20-min intervals throughout the entire study. Insulin secretion rates were derived from C-peptide levels by deconvolution. Sleep was polygraphically monitored. During nocturnal sleep, levels of glucose and insulin secretion increased by 31 +/- 5% and 60 +/- 11%, respectively, and returned to baseline in the morning. During sleep deprivation, glucose levels and insulin secretion rose again to reach a maximum at a time corresponding to the beginning of the habitual sleep period. The magnitude of the rise above morning levels averaged 17 +/- 5% for glucose and 49 +/- 8% for calculated insulin secretion. Serum insulin levels did not parallel the circadian variation in insulin secretion, indicating the existence of an approximate 40% increase in insulin clearance during the night. Daytime sleep was associated with a 16 +/- 3% rise in glucose levels, a 55 +/- 7% rise in insulin secretion, and a 39 +/- 5% rise in serum insulin. The diurnal variation in insulin secretion was inversely related to the cortisol rhythm, with a significant correlation of the magnitudes of their morning to evening excursions. Sleep-associated rises in glucose correlated with the amount of concomitant growth hormone secreted. These studies demonstrate previously underappreciated effects of circadian rhythmicity and sleep on glucose levels, insulin secretion, and insulin clearance, and suggest that these effects could be partially mediated by cortisol and growth hormone. PMID- 1885779 TI - Dietary fish oil-induced changes in intrahepatic cholesterol transport and bile acid synthesis in rats. AB - Hepatic cholesterol metabolism was studied in rats fed purified diets supplemented (9% wt/wt) with either fish oil (FO) (n-3 fatty acids) or corn oil (CO) (n-6 fatty acids) for 4 wk. Rats were equipped with permanent catheters in heart, bile duct, and duodenum to allow studies under normal feeding conditions. [3H]-cholesteryl oleate-labeled small unilamellar liposomes, which are rapidly endocytosed by hepatocytes, were intravenously injected to label intrahepatic cholesterol pools, and plasma and bile were collected. FO as compared to CO induced a lowering of plasma cholesterol levels by 38% and of triglyceride levels by 69%. This reduction in plasma lipids in FO rats was accompanied by: (a) an increased bile acid pool size (28%); (b) a fourfold increase in the ratio cholic acid/chenodeoxycholic acid in bile; (c) increased biliary excretion of cholesterol (51%); (d) accelerated excretion of endocytosed free cholesterol into bile; (e) accelerated incorporation of endocytosed cholesterol in bile acids; (f) a significant increase in the bile acid-independent fraction of bile flow; and (g) a threefold increase in hepatic alkaline phosphatase activity. The results show that FO induces changes in transport and metabolic pathways of cholesterol in the rat liver, which result in a more rapid disposition of plasma-derived cholesterol into the bile. PMID- 1885780 TI - Luminal vasopressin modulates transport in the rabbit cortical collecting duct. AB - We explored the action of luminal AVP in rabbit CCD perfused in vitro at 37 degrees C. Nanomolar concentrations of luminal AVP induced a sustained hyperpolarization of transepithelial voltage (Vt) in contrast to a transient hyperpolarization caused by basolateral AVP. 10 microM basolateral ouabain abolished the latter but not the former change in Vt. Despite a sustained hyperpolarization (from -20.7 +/- 2.9 to -34.1 +/- 4.7 mV; P less than 0.01), 10 nM luminal AVP only slightly altered net Na+ and K+ fluxes (7.6% stimulation and no significant change, respectively). Instead, luminal AVP appeared to modulate an acetazolamide-sensitive electrogenic ion transport because 200 microM basolateral acetazolamide suppressed the luminal AVP-induced hyperpolarization (percentage of Vt from -50.4 +/- 10.8 to -5.1 +/- 1.4; P less than 0.005). In terms of water transport, 10 nM luminal AVP did not change hydraulic conductivity (Lp, x 10(-7) cm/atm per s) (from 3.9 +/- 0.8 to 5.0 +/- 1.2), but suppressed the increase in Lp induced by 20 pM basolateral AVP (134.9 +/- 19.2 vs. 204.3 +/- 21.1 in control; P less than 0.05). These findings demonstrate distinct luminal action of AVP, suggesting amphilateral regulation of epithelial transport by AVP in the CCD. PMID- 1885782 TI - Metabolism of prostaglandin F2 alpha in Zellweger syndrome. Peroxisomal beta oxidation is a major importance for in vivo degradation of prostaglandins in humans. AB - We have recently shown in vitro that the peroxisomal fraction of a rat liver homogenate has the highest capacity to beta-oxidize prostaglandins. In order to evaluate the relative importance of peroxisomes for this conversion also in vivo, we administered [3H]prostaglandin F2 alpha to an infant suffering from Zellweger syndrome, a congenital disorder characterized by the absence of intact peroxisomes. As a control, labeled compound was administered to two healthy volunteers. Urine was collected, fractionated on a SEP-PAK C18 cartridge, and subjected to reversed-phase high-performance liquid chromatography. The Zellweger patient was found to excrete prostaglandin metabolites considerably less polar than those of the control subjects. The major urinary metabolite in the control subjects was practically absent in the urine from the Zellweger patient. The major urinary prostaglandin F2 alpha metabolite from the Zellweger patient was identified as an omega-oxidized C20-prostaglandin, 9,11-dihydroxy-15-oxoprost-5 ene-1,20-dioic acid. The major urinary prostaglandin F2 alpha metabolite from the control subjects had chromatographic properties of a tetranor (C16) prostaglandin, in accordance with earlier published data. The present results, in combination with our previous in vitro data, indicate that peroxisomal beta oxidation is of major importance for in vivo chain shortening of prostaglandins. PMID- 1885784 TI - Cross-sectional radiography for implant site assessment. AB - An accurate tomographic technique is described for acquisition of optimal cross sectional images of implant sites before implant surgery. The described technique is applicable to tomographic systems equipped with a cephalometric head positioner. This cross-sectional tomographic technique was performed on a series of patients and the images of the first 20 patients subsequently evaluated. The cross-sectional images allowed for the characterization of the alveolar crest and visualization of anatomic structures in a buccolingual dimension while providing an accurate estimation of available vertical space from the crest. PMID- 1885781 TI - Effects of fat on insulin-stimulated carbohydrate metabolism in normal men. AB - We have examined the onset and duration of the inhibitory effect of an intravenous infusion of lipid/heparin on total body carbohydrate and fat oxidation (by indirect calorimetry) and on glucose disappearance (with 6,6 D2 glucose and gas chromatography-mass spectrometry) in healthy men during euglycemic hyperinsulinemia. Glycogen synthase activity and concentrations of acetyl-CoA, free CoA-SH, citrate, and glucose-6-phosphate were measured in muscle biopsies obtained before and after insulin/lipid and insulin/saline infusions. Lipid increased insulin-inhibited fat oxidation (+40%) and decreased insulin stimulated carbohydrate oxidation (-63%) within 1 h. These changes were associated with an increase (+489%) in the muscle acetyl-CoA/free CoA-SH ratio. Glucose disappearance did not decrease until 2-4 h later (-55%). This decrease was associated with a decrease in muscle glycogen synthase fractional velocity ( 82%). The muscle content of citrate and glucose-6-phosphate did not change. We concluded that, during hyperinsulinemia, lipid promptly replaced carbohydrate as fuel for oxidation in muscle and hours later inhibited glucose uptake, presumably by interfering with muscle glycogen formation. PMID- 1885785 TI - The regeneration of electroreceptors in Kryptopterus. AB - The regeneration of ampullary electroreceptors was studied in the living catfish, Kryptopterus, by differential interference contrast optics. Electroreceptors in this transparent catfish are found, among other places, along the proximal portion of each anal fin ray, while the distal portion does not contain electroreceptors. Upon interruption of the sensory innervation, the electroreceptors disappear but regenerate when the skin is reinnervated. In this study, we tested the role of the skin and nerve in receptor regeneration with the following two experiments. First, a plug of fin containing electroreceptors was removed to determine whether electroreceptors could form in regenerated skin after the complete removal of all of the receptors within an interradial zone of the anal fin. Second, a portion of anal fin that contained electroreceptors was excised and a graft of electroreceptor-free (EF) fin was sutured in its place to determine whether epidermis that does not normally contain these receptors can be induced to form them. These grafts were compared to control grafts taken from proximal electroreceptor-containing (EC) fin. By 2 weeks following surgery, receptors were found in regenerated fin tissue and within the EC grafts. Electroreceptors also formed within most of the EF grafts. As electroreceptor regeneration does not require the presence of degenerated organs, and as electroreceptors can form in fin that normally does not contain receptors, we suggest that the formation of electroreceptors does not require old target sites and that epidermal cells can be induced to form receptors upon contact by regenerating axons. We discuss as well the factors that influence the pattern of receptor reappearance. PMID- 1885783 TI - Chylomicron-retinyl palmitate clearance in type I hyperlipidemic families. AB - Our primary aim was to determine the extent to which intraplasmic retinyl palmitate (RP) transfers to other lipoprotein particles when chylomicron remnants are not produced and/or the plasma RP residence time is increased. The study was conducted on three familial type I hyperlipoproteinemic patients, four lipoprotein lipase (LpL)-deficient heterozygotes, and three controls on a metabolic research unit. To each subject, a fat load was administered containing 16% of total daily calories in type I patients, 40% in heterozygotes and controls, plus 60,000 U/m2 vitamin A. Triglyceride (TG) and RP levels were evaluated in chylomicron and nonchylomicron fractions. Delay in the clearance of chylomicron fraction RP and the marked deficiency in nonchylomicron-RP (presumed lack of remnant production) in all three type I patients suggests that RP does not demonstrate significant intraplasmic transfer from chylomicrons to existent apolipoprotein B100 particles. In contrast to noncoincident TG and RP peaking in the normal subject, heterozygotes were found to demonstrate coincident plasma TG and RP curves, which is consistent with a common catabolic pathway for both TG and RP and inconsistent with intraplasmic RP transfer. This corroborates reports on compromised chylomicron clearance in heterozygotes. We conclude that RP is an appropriate representative marker for intestinally derived particles in LpL deficient or partially deficient individuals. PMID- 1885786 TI - Patterning in the regeneration of electroreceptors in the fin of Kryptopterus. AB - The influence of the target tissue on afferent nerve regeneration was studied in the adult glass catfish, Kryptopterus. In this fish, electroreceptors in the anal fin are distributed in a characteristic pattern in the proximal part of the fin and are absent in the distal portion of the fin. We tested whether axons were more likely to induce electroreceptors in certain regions of fin epidermis than in others. We rotated fin transplants so that the location of the degenerating electroreceptors was altered with respect to the regenerating axons in the host tissue dorsal to the fin. The effects of these rotations were observed in the living animal with differential interference contrast optics over a period of 10 weeks. When transplants were reversed rostrocaudally, new electroreceptors formed in the caudal half of the interradial zone, where degenerating electroreceptors were at the time of transplantation. When transplants were rotated so that the dorsoventral and rostrocaudal axes were reversed, some new receptors formed in the old target site regions that were located in the caudal interradial zones (in the distal half of the graft with respect to the host). Regenerating axons reached these regions of the transplant by taking unusual routes around the electroreceptor-free regions of fin. Very few electroreceptors formed in the distal/caudal or proximal/caudal interradial quadrants of grafts where the original orientation of the tissue was maintained. We suggest that old target sites have a neurotropic influence on the regenerating afferent axons and discuss the possibility that the distal fin epidermis is not as permissive to electroreceptor formation as proximal fin epidermis. PMID- 1885787 TI - Representation of the body by single neurons in the dorsolateral striatum of the awake, unrestrained rat. AB - Single cell recordings in awake monkeys and cats have demonstrated that individual body parts are represented within striatal subregions receiving projections from somatic sensorimotor cortex. Literature indicating that the lateral striatum of the rat receives similar cortical inputs and subserves sensorimotor functions prompted a study of whether this subregion contains similar representations of the body. Single cell recordings were obtained from 923 neurons of 24 awake, unrestrained rats. Of 788 neurons categorized according to body part, 264 (34%) discharged in relation to active movement, passive manipulation, and/or cutaneous stimulation of a particular part of the body; the remainder were related to global, whole body movement (38%) or were unresponsive (28%). Neurons related to individual body parts were recorded throughout the entire anterior-posterior extent of the dorsolateral striatum (+1.60 to -2.12 mm A-P, from bregma), intermingled among each other in all 3 dimensions. Two topographic arrangements were observed. First, neurons that fired rhythmically, in phase with low frequency (5-6 Hz) whisking of the vibrissae were segregated in the caudal striatum (-0.2 to -2.12 mm A-P) from neurons related to other body parts, which were distributed from +1.6 to -0.8 mm A-P. Second, representations of the head and face were located ventral to those of the limbs, despite substantial overlap in their overall distributions. A prominent feature of individual electrode tracks was the clustering together of cells related to the same body part. Neurons related to body parts exhibited substantial diversity, which took several distinct forms. Some neurons fired during movement or sensory stimulation in any direction, whereas others showed selectivity for a particular direction. Certain neurons responded to sensory stimulation of a large unilateral region of the body (e.g., all vibrissae or the entire forelimb), whereas others responded to stimulation of highly restricted regions (e.g., a single vibrissa or a single forepaw digit). Finally, neurons differed in the extent to which they exhibited active and passive properties. Among vibrissae-related neurons, one group fired rhythmically during whisking but did not respond to sensory stimulation of the vibrissae; a second group responded to sensory stimulation of the vibrissae but did not fire rhythmically during whisking; a third group showed both properties. Among limb-related neurons, firing during active movement was a property of every cell; none showed sensory responsiveness without showing a relation to active movement of one limb. Of the limb-related neurons, 89% tested responded to passive manipulation of the limb to which the neuron was actively related, and 71% also responded to cutaneous stimulation.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1885788 TI - Neurogenesis in the brain auditory pathway of a marsupial, the northern native cat (Dasyurus hallucatus). AB - Neurogenesis in the auditory pathway of the marsupial Dasyurus hallucatus was studied. Intraperitoneal injections of tritiated thymidine (20-40 microCi) were made into pouch-young varying from 1 to 56 days pouch-life. Animals were killed as adults and brain sections were prepared for autoradiography and counterstained with a Nissl stain. Neurons in the ventral cochlear nucleus were generated prior to 3 days pouch-life, in the superior olive at 5-7 days, and in the dorsal cochlear nucleus over a prolonged period. Inferior collicular neurogenesis lagged behind that in the medial geniculate, the latter taking place between days 3 and 9 and the former between days 7 and 22. Neurogenesis began in the auditory cortex on day 9 and was completed by about day 42. Thus neurogenesis was complete in the medullary auditory nuclei before that in the midbrain commenced, and in the medial geniculate before that in the auditory cortex commenced. The time course of neurogenesis in the auditory pathway of the native cat was very similar to that in another marsupial, the brushtail possum. For both, neurogenesis occurred earlier than in eutherian mammals of a similar size but was more protracted. PMID- 1885789 TI - Semiautomated ROI analysis in dynamic MR studies. Part I: Image analysis tools for automatic correction of organ displacements. AB - The most important problem in the analysis of time sequences is the compensation for artifactual motion. Owing to motion, medical images of the abdominal region do not represent organs with fixed configuration. Analysis of organ function with dynamic contrast medium studies using regions of interest (ROIs) is thus not readily accomplished. Images of the organ of interest need to be registered and corrected prior to a detailed local analysis. We have developed an image analysis scheme that allows the automatic detection of the organ contours, the extraction of the motion parameters per frame, and the registration of images. The complete procedure requires only minimal user interaction and results in a readjusted image sequence, where organs of interest remain fixed. Both a visual analysis of the dynamic behavior of functional properties and a quantitative statistical analysis of signal intensity versus time within local ROIs are considerably facilitated using the corrected series. PMID- 1885790 TI - Semiautomated ROI analysis in dynamic MR studies. Part II: Application to renal function examination. AB - Fast MR techniques and the application of water-soluble contrast agents allow the simultaneous examination of renal morphology and the functional aspects of glomerular filtration using bolus injections of Gd-DTPA. Spatial resolution is sufficient to resolve individual renal pyramids, but the quantitative examination of regions of interest (ROIs) is severely impeded by organ movements due to variations of the end-inspiratory position. A new image-processing scheme has been used and tested in 23 normal volunteers and patients. This scheme replaces a tedious frame-by-frame ROI analysis by positional correction of renal regions of all frames of the sequence such that the definition of the regions has to be performed only once. The signal intensities (SIs) of the local regions in each frame are used to compute statistics and to generate curves representing local temporal SI changes due to contrast agent excretion. The success rate of the procedure depends largely on the image quality and on the adherence to a proved acquisition protocol. The present article shows that the combination of MR and robust and reliable image-processing methods can be important for the highly automated analysis of a large number of images acquired as dynamic studies. PMID- 1885791 TI - Standardized quantitative high resolution CT in lung diseases. AB - Twenty-seven patients with diffuse fibrosing alveolitis (DFA), 27 patients with granulomatous lung disease (GLD), 3 patients with homozygous alpha 1-proteinase inhibitor deficiency (alpha 1-PID), and 6 healthy volunteers (C) were studied using thin section high resolution CT (HRCT) at 50% of actual vital capacity (VC), determined and controlled spirometrically during each exposure. A fast contour tracing algorithm was used to isolate the lung parenchyma followed by a quantitative histogram analysis of the frequencies of CT values. Mean CT values enabled us to discriminate significantly between the groups of C and alpha 1-PID. Significant differences were found between the groups of GLD and DFA versus C by applying suitably selected intervals of CT values. Moreover, if the patients were assigned to four different groups according to their lung function results (normal, restrictive, obstructive, restrictive and obstructive), again significant differences existed with respect to defined intervals of CT values. Mean CT values showed a significant negative correlation with lung function tests representative of lung parenchymal disease, i.e., VC, diffusing capacity, and exercise PaO2. Moreover, CT values ranging from -899 to -800 HU correlated positively, whereas CT value frequencies above -699 HU correlated inversely with these same lung function parameters. These results indicated that certain intervals of CT values do reflect functionally different abnormalities of lung parenchyma. It is concluded that an analysis of frequencies of CT values determined by spirometrically standardized HRCT provides objective quantitative data that reflect changes of pulmonary structure corresponding to lung function impairments. Thus, spirometrically standardized HRCT may be helpful for evaluating and staging patients with diffuse pulmonary disease. PMID- 1885792 TI - Endobronchial lipoma: CT diagnosis. AB - Computed tomography was performed in two patients with endobronchial lipomas. Bronchoscopy was inconclusive, but CT provided the definitive diagnosis by demonstrating fat within the endobronchial tumor. PMID- 1885793 TI - MR imaging of partial anomalous pulmonary venous connections. AB - Magnetic resonance imaging was performed on 11 patients with partial anomalous pulmonary venous connections (PAPVC). Ten of these patients also had echocardiographic examinations, eight of which included color-flow Doppler studies. The diagnosis of PAPVC was confirmed in each of these patients by surgery or angiography. Fourteen anomalous pulmonary venous connections were identified, 10 involving the right upper lobe pulmonary vein and 4 involving the left upper lobe pulmonary vein. This retrospective review demonstrated that all 14 anomalous venous connections were correctly identified by MR imaging, whereas only 8 of 13 (62%) were identified by echocardiography. With MR, 89% of all the pulmonary veins and 93% of the anomalous pulmonary veins were visualized on axial images, while 41% of all pulmonary veins and 71% of anomalous veins were seen on coronal MR images. There were five atrial septal defects (ASDs), four of the sinus venous type and one of the septum secundum type. All five ASDs were correctly identified with MR imaging; three of four ASDs were identified with echocardiography. We conclude that MR imaging provides an accurate noninvasive method of depicting the anatomic abnormalities associated with PAPVC. PMID- 1885795 TI - Staging of urinary bladder neoplasms with MR imaging: is Gd-DTPA helpful? AB - This study was performed to investigate whether intravenous administration of Gd DTPA can improve the accuracy of MR imaging in the detection and staging of bladder neoplasms. In 68 patients with suspected urinary bladder neoplasms, MR examinations were performed with T1-weighted SE sequences before and after intravenous administration of Gd-DTPA. The findings were compared with surgical staging using the TNM classification. Overall staging accuracy of contrast enhanced MR was 46%; if stages Ta-T3a were combined into one group, the accuracy was 69%. Accuracy was low (19%) in tumors without muscular bladder wall invasion (Ta). In cases with extravesical spread (greater than or equal to T3b), the accuracy of staging was 87%. Contrast enhanced MR detected extravesical extension of tumor with a sensitivity of 93% and a specificity of 95%. Contrast enhancement increased the sensitivity for detection of urinary bladder neoplasms from 70% on precontrast T1-weighted scans to 79% on postcontrast scans. In comparison with T2 weighted scans, the Gd-DTPA enhanced T1-weighted scans had better image quality and lower acquisition times. PMID- 1885796 TI - Improving the accuracy of digital CT pelvimetry. AB - Digital pelvimetry is performed to assess the feasibility of vaginal breech delivery. This provides measurements of the anteroposterior inlet, transverse inlet, and interspinous distance. The transverse inlet measurement determined from an anteroposterior ScoutView can be inaccurate if its level is not at the gantry isocenter. Using a simple geometric argument, the theoretical error of this measurement is calculated and a method provided to allow for correction of this error. PMID- 1885794 TI - CT of fundoplication. AB - To determine the CT findings postfundoplication, we retrospectively compared CT in 22 postfundoplication patients with CT in 22 patients with unrepaired hiatal hernias and gastroesophageal (GE) junction abnormalities and 24 patients with gastric or esophageal carcinoma involving the GE junction. Seventeen of the 22 postfundoplication patients had undergone a Nissen procedure. Of the 22 patients, 11 had esophageal dilatation, 14 had GE junction masses, 4 had esophageal wall thickening, 7 had surgical clips, and none had hepatic metastases or upper abdominal lymphadenopathy. Statistically, on CT, postfundoplication patients are more likely to have a GE junction mass (p = 0.023) and least likely to have wall thickening (p = 0.021). Nonetheless, because the findings occur frequently in each group, they are not diagnostic in the individual patient. However, 11 of 12 post-Nissen masses had the unique finding of an oval or linear central fat density within the mass. This finding was absent in the other postfundoplication masses and in those patients with repaired hiatal hernia or tumor. We conclude that pseudomasses occur on CT postfundoplication and can be indistinguishable from hiatal hernias and GE junction neoplasms unless a central fat density is present. PMID- 1885798 TI - Coronal MR imaging for visualization of wallerian degeneration of the pyramidal tract. AB - A coronal image taken along a straight line between the front edge of the medulla and the deepest point of the interpeduncular cistern clearly displayed wallerian degeneration of the segment of the pyramidal tract between the internal capsule and the pons, the medulla, or the decussation. This visualization was verified in 21 patients with moderate or severe hemiparesis following a stroke episode. PMID- 1885799 TI - Curvilinear and tubulonodular varieties of lipoma of the corpus callosum: an MR and CT study. AB - Until recently all callosal lipomas were grouped together. However, these lipomas can be clearly separated into two groups having different morphologies and associated brain anomalies. One group consists of anteriorly situated round or cylinder-shaped lipomas, termed tubulonodular. These lipomas are generally greater than 2 cm in diameter and have a high incidence of corpus callosum dysgenesis, frontal lobe anomalies, and frontal encephaloceles. The second group comprises thin, posteriorly situated lipomas curving around the splenium and are termed curvilinear. The curvilinear lipomas are generally associated with a normal corpus callosum and otherwise have a low incidence of associated anomalies. When anomalies do occur, they tend to be less severe than with the tubulonodular lipomas. We present four cases of curvilinear lipomas and review similar cases in the literature to explain why lipomas of the callosal region have such a variety of associated anomalies and morphologies. Our findings support the idea that both groups of lipomas develop in the region of the origin of the corpus callosum but form at different times during gestation, with the tubulonodular ones forming earlier and thus being associated with more severe cerebral anomalies. PMID- 1885797 TI - FDG-PET in the selection of brain lesions for biopsy. AB - The CT-guided stereotaxic needle biopsy has become a widely used procedure in the diagnostic evaluation of intracranial lesions including tumors. Conventional CT or MR frequently defines the anatomic regions of abnormality, which may be multiple lesions or a single lesion that is heterogeneous in cellular composition owing to the topographic variation of cellular constituency or the combination of active disease, nonspecific inflammation, necrosis, and/or edema. In these cases, selection of the most appropriate site for a successful diagnostic needle biopsy can be difficult. In three patients, we have used [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) to determine the site most likely to provide a diagnostic biopsy result. In the first patient, who presented with confusion, multiple biopsies from the temporal lobe, based on MR abnormalities, revealed only reactive gliosis and edema. Repeat biopsy directed by PET revealed an anaplastic astrocytoma. In a second patient, PET allowed us to differentiate radiation effect from active metastatic breast cancer. In the third patient, who presented with a grand mal seizure, biopsy of a CT-defined hypodense region demonstrated lymphocytosis. Metabolism of FDG was normal or increased in areas of Aspergillus encephalitis at autopsy. These preliminary studies suggest a complementary role for FDG-PET and CT or MR in selected patients for defining the intracranial site most likely to yield a positive biopsy result. PMID- 1885800 TI - SPECT and MR imaging in herpes simplex encephalitis. AB - Two cases of necrotizing herpes simplex encephalitis (HSE) were investigated with 99mTc-hexamethylpropyleneamineoxime (HMPAO) SPECT and MR. The clinical course was compared with the neuroimaging results. In the acute stage, the increased HMPAO uptake matched the MR hyperintense signal in the limbic temporal lobe and in the basal ganglia. Protracted inflammation was accompanied by persistently high HMPAO uptake. The sequelae of HSE were characterized by decreased HMPAO uptake and postnecrotic widening of the temporal horns. The "limbic" pattern recognized in both SPECT and MR reflects the basic pathophysiology and neuropathology of HSE. Both methods may be useful in the diagnosis and follow-up of HSE. PMID- 1885801 TI - Brain perfusion studies by xenon-enhanced CT using washin/washout study protocols. AB - Very short inhalation times and short total examination times are desirable in cerebral blood flow measurements by xenon enhanced CT to minimize the possibility of flow activation and--more importantly for practical purposes--the probability of patient motion due to the effects of xenon. We have investigated washin/washout procedures and have compared them with conventional washin scanning protocols by simulation and in clinical studies. Examination protocols with only 3 min of inhalation and up to eight scans, all taken at 1 min intervals, provide flow estimates with smaller SDs than would be obtained for washin studies taken with the same total radiation dose. Compared with a standard 8 min washin procedure, a 3 min washin/5 min washout study using the same dose yields an SD reduction by a factor of 1.3 for low flow areas and of 1.8 for high flow gray matter. A 3 min washin/3 min washout study, employing only 78% of the dose of an 8 min washin study, will still provide an SD reduction factor of 1.7 in gray matter. These results have been confirmed qualitatively by studies carried out both in volunteers and in patients. PMID- 1885802 TI - Retropharyngeal mass as a rare presentation of a goiter: CT findings. AB - When sufficiently large, goiters often extend into the mediastinum. Less often, there is extension into the tracheoesophageal groove and the retroesophageal space, and, rarely, there may be growth into the retropharyngeal space. In the latter instance the goiter will present clinically as an oropharyngeal mass in a patient with stridor. We report two similar cases documented with CT studies that clearly show that the origin of the retropharyngeal mass was the thyroid gland. PMID- 1885804 TI - Demonstration of an early draining vein by MR angiography. AB - We present a case of an arteriovenous malformation (AVM) where standard MR angiography demonstrated an enlarged basal vein of Rosenthal. The lenticulostriate branches of the middle cerebral artery were suggested but not conclusively shown, as the feeders of the AVM. Therefore, it could not be determined whether the enlarged vein was part of an AVM or of a venous angioma. By using a saturation pulse inferior to the image volume including the basal vein of Rosenthal and the middle cerebral artery, the transmission of "black blood" to the basal vein of Rosenthal was demonstrated. This implied early venous draining, which confirmed that the lesion represented an AVM. PMID- 1885803 TI - CT evaluation of chondromatosis of the temporomandibular joint. AB - The CT findings in two cases of chondromatosis of the temporomandibular joint are described. The distinctive feature of the first case was the presence of ossified loose bodies surrounding the head of the condyle, whereas in the second there was clear evidence of arthrosis. Three-dimensional image reconstruction was also used in the first case to obtain a better overall visualization of the changes. PMID- 1885805 TI - Regression of pituitary macroadenoma after pituitary apoplexy: CT and MR studies. AB - We present a case of a patient with apoplexy due to infarction of a large pituitary macroadenoma. Conservative treatment with steroids resulted in reversal of symptoms and the adenoma involuted. This suggests that medical management may be sufficient therapy in some patients with this complication. PMID- 1885806 TI - Wernicke encephalopathy: follow-up study by CT and MR. AB - A follow-up study by CT and MR of a case of Wernicke encephalopathy is reported. In the early stages, CT and MR revealed a characteristic topographical distribution of lesions in the midbrain, pons, and thalami. In the later stages, MR showed atrophy of the mamillary bodies and midbrain tegmentum and dilatation of the third ventricle. Both CT and MR are useful tools for the diagnosis of Wernicke encephalopathy in the early stages. PMID- 1885807 TI - Chronic osteomyelitis with epidural abscess: CT and MR findings. AB - A case of chronic osteomyelitis in the occipital bone associated with underlying chronic epidural abscess was diagnosed by skull radiography, CT, and MR. Skull radiography showed diffuse sclerosis of the occipital bone and dural calcifications. Computed tomography demonstrated thickened sclerotic changes of the osteomyelitic area, dural calcifications, and epidural fluid collection. The area of chronic osteomyelitis displayed, essentially, no signal intensity in the T1-weighted and T2-weighted MR images. The chronic epidural abscess had heterogeneous signal intensity on T1-weighted images and good enhancement after Gd-diethylenetriamine pentaacetic acid administration. On T2-weighted images the abscess had relatively homogeneous high signal intensity. PMID- 1885808 TI - Malignant thymoma in an ectopic thymus: CT appearance. AB - To our knowledge, malignant thymoma arising from an ectopic thymus gland has not been reported. Described below is such a case. PMID- 1885809 TI - Massive hepatic necrosis in the HELLP syndrome: CT correlation. AB - We present a patient with toxemia of pregnancy and the HELLP syndrome [hemolysis (H), elevated liver enzymes (EL), and a low platelet count (LP)] resulting in massive hepatic necrosis. Cross-sectional imaging, including sonography, computed tomography, and nuclear medicine, was instrumental in the diagnosis and differentiation from hepatic abnormalities of other pregnancy related entities especially acute fatty liver of pregnancy. PMID- 1885810 TI - Hepatic focal nodular hyperplasia: diagnosis by ultrafast Gd-DTPA enhanced FLASH MR. AB - The utility of gadolinium-enhanced ultrafast MR imaging in the diagnosis of focal nodular hyperplasia (FNH) of the liver was assessed in one patient. Contrast enhanced serial snapshot-FLASH with a frequency of 30 images/min demonstrated the typical hemodynamic appearance of FNH known from CT studies. PMID- 1885811 TI - CT, US, and MR imaging of hepatic aspergilloma. PMID- 1885812 TI - Amyloidosis: CT appearance of calcified, enlarged periaortic lymph nodes. AB - The radiographic demonstration of lymph node involvement in amyloidosis is rare. We report a case of calcified, enlarged perioartic and mediastinal lymph nodes detected by CT. PMID- 1885813 TI - MR imaging of Asherman syndrome: total endometrial obliteration. AB - We present a case of Asherman syndrome involving severe intrauterine adhesions in a 31-year-old woman. Findings at hysterosalpingography and hysteroscopy are correlated with MR findings. PMID- 1885815 TI - Focal hypoplasia of the tentorium with temporal lobe herniation: CT demonstration. PMID- 1885816 TI - MR diagnosis of a right cervical aortic arch. PMID- 1885814 TI - CT demonstration of acute and chronic iliofemoral thrombosis. AB - A case of bilateral iliofemoral vein thrombosis in a young man, secondary to testicular seminoma, is presented. Both the acute and chronic thrombus were detectable on abdominopelvic CT without contrast enhancement, and the mechanisms responsible for the differing appearances of the thrombi are discussed. Detection of thrombi in this way may avoid the administration of contrast medium. PMID- 1885817 TI - Superior mesenteric artery occlusion: an unenhanced CT finding. PMID- 1885818 TI - Rapid NMR cardiography with a half-echo M-mode method. AB - A real-time NMR cardiac profiling pulse sequence has been developed that incorporates two-dimensional (2D) selective excitation and a half-echo readout. The time resolution has been improved by a factor of two relative to the previous flow-compensated, full-echo version. The technique produces a 2D plot of "beam" axis position versus time, analogous to M-mode echocardiography. In human subjects, details of valve leaflet motion, intracardiac flow, wall motion, and wall thickening may be observed along optimal lines of sight selected interactively. The pulse sequence uses a low-tip-angle 2D selective-excitation pulse derived from a spiral k-space trajectory to excite a narrow cylinder of magnetization, followed by a half-echo readout gradient oriented along the axis of the cylinder. One-dimensional Fourier transformation of the acquired signal results in a magnetization profile along the length of the cylinder, or beam. The pulse sequence is effectively flow compensated without any additional gradient lobes, because the rapid oscillation in the gradient wave forms of the 2D excitation pulse produces relatively small net gradient moments, and the shortened readout gradient has minimal first-order moment relative to center echo. The signal from moving blood can alternatively be velocity encoded by the addition of bipolar gradients along any of the three axes, producing Doppler-like traces of intracardiac blood flow. PMID- 1885819 TI - Three-dimensional volumetric display of CT data: effect of scan parameters upon image quality. AB - Of the many steps involved in producing high quality three-dimensional (3D) images of CT data, the data acquisition step is of greatest consequence. The principle of "garbage in, garbage out" applies to 3D imaging--bad scanning technique produces equally bad 3D images. We present a formal study of the effect of two basic scanning parameters, slice thickness and slice spacing, on image quality. Three standard test objects were studied using variable CT scanning parameters. The objects chosen were a bone phantom, a cadaver femur with a simulated 5 mm fracture gap, and a cadaver femur with a simulated 1 mm fracture gap. Each object was scanned at three collimations: 8, 4, and 2 mm. For each collimation, four sets of scans were performed using four slice intervals: 8, 4, 3, and 2 mm. The bone phantom was scanned in two positions: oriented perpendicular to the scanning plane and oriented 45 degrees from the scanning plane. Three-dimensional images of the resulting 48 sets of data were produced using volumetric rendering. Blind review of the resultant 48 data sets was performed by three reviewers rating five factors for each image. The images resulting from scans with thin collimation and small table increments proved to rate the highest in all areas. The data obtained using 2 mm slice intervals proved to rate the highest in perceived image quality. Three millimeter slice spacing with 4 mm collimation, which clinically provides a good compromise between image quality and acquisition time and dose, also produced good perceived image quality. The studies with 8 mm slice intervals provided the least detail and introduced the worst inaccuracies and artifacts and were not suitable for clinical use. Statistical analysis demonstrated that slice interval (i.e., table incrementation) was of primary importance and slice collimation was of secondary, although significant, importance in determining perceived 3D image quality. PMID- 1885820 TI - Head holder for PET, CT, and MR studies. AB - A new head holder for the fixation and repositioning of the patient head in PET, CT, and MR scanners has been designed and tested. With this device, a bidimensional correlation between functional and anatomical brain images can also be obtained. Head fixation and repositioning are achieved using the patient's dental morphology as an anatomical reference. With a dentistic material, a mold of the patient's teeth is obtained in a few minutes. The molding substance rests on a plastic support, fixed to the head holder. Each time the patient undergoes a new study, his/her personal mold is used, ensuring accurate head repositioning. External markers fixed on the head holder (made visible in lateral PET and CT projection images, midsaggital MR images, and also on the axial images) make it possible to record and recognize the angular orientation and the position of the brain in the three-dimensional space, to correlate images of the same patient obtained with different neuroimaging modalities, and to accurately reposition patients for follow-up studies. The head holder was tested on several subjects. Fixation and repositioning accuracy of within 2.5 mm were achieved in the three dimensional space. Orientation accuracy was 1 degree. PMID- 1885821 TI - Physical aspects of cardiac scanning with a block detector positron tomograph. AB - Physical aspects relating to cardiac scanning are described for an eight ring (15 plane) positron tomograph consisting of BGO block detectors (CTI/Siemens 931 08/12). Performance parameters were derived from a cylindrical heart phantom having a "myocardial" wall of thickness varying from 3 mm to 27 mm. This phantom was inserted into a chest phantom consisting of simulated chest wall, lungs, and arms. Recovery coefficients for myocardial thicknesses of 10 mm and 15 mm were 0.75 and 0.9, respectively. Division by the transmission minus "blood pool" (extravascular density) image was found to give a variation of corrected myocardial counts within +/- 5% when transmission data were smoothed. The on-line dead time correction algorithm was found to be accurate to within 5% up to 20 mCi (740 MBq) in the axial field of view (FOV) (10.8 cm) in the central chamber of the heart phantom. However, the correction factor at this rate is approximately 3, which would imply poor use of administered dose. Counts in the image due to scatter are approximately 2% in the (cold) central cavity of the heart phantom relative to counts/pixel in the active myocardium. The presence of phantom arms in the FOV was found to have only a small effect on mean pixel counts and noise in the heart phantom image, as did movement of the arms within a reasonable range. PMID- 1885822 TI - [Computer-assisted creation and fabrication of ceramic inlays and veneers]. AB - The application of computers in restorative dentistry make it possible to fabricate ceramic restorations. The dental CAD/CAM system CEREC (Siemens AG Co.) is available to produce inlays and veneers in the dental office in a single appointment. PMID- 1885823 TI - [Isolated cleft palates compared to cleft palates associated with Pierre Robin syndrome]. AB - The purpose of this study was to evaluate two variables associated with isolated cleft palate and cleft palate related to Pierre Robin syndrome, namely, sexual incidence and dental anomalies. The study demonstrated that there are more dental anomalies associated with the Pierre Robin syndrome and that girls are more affected than boys in both instances. PMID- 1885824 TI - [Oral health of 15-year-old students living in non-fluoridated public school sectors on l'Ile de Montreal in 1987]. AB - Using data from a cross-sectional survey on 570 fifteen year old students living in non-fluoridated public school sectors on the Island of Montreal in 1987, the effect of terminating the restorative aspect of public dental health care insurance for twelve to fifteen year old students is examined. This study also highlights the level and quality of dental caries treatment on the twelve to fifteen year old group. The main point to be made is that there was an improvement in the DMFT index values of fourteen and fifteen year old students in metropolitan areas. In reality, fourteen year old children had a DMFT index of 6.45 in 1983-1984, while the fifteen year old children in the 06A region (non fluoridated area) had a DMFT of 6.07 in 1987. Since the metropolitan fluoridated area had been eliminated from the results in 1987, it is quite obvious that the 6.07 result obtained overestimates the actual prevalence of dental caries in the metropolitan area in 1987. On the other hand, the progress which had been recorded between 1977 and 1984 by francophones in relation to anglophones was partially lost in 1987. Furthermore, this study has demonstrated that the prevalence and level of dental caries treatment are highly associated with the language spoken at home and also with the family's socio-economic status. PMID- 1885825 TI - Newer variants and simulants of basal cell carcinoma. AB - Basal cell carcinoma (BCC) has characteristic clinical and histopathologic findings that facilitate accurate diagnosis. There are, however, many variants and simulants of BCC that may cause clinical and/or histopathologic confusion. These entities often have features in common with BCC, with nodular or sclerosing basaloid islands, peripheral palisading, stromal retraction, (pseudo)-glandular formation, and/or prominent mucin. Recently described BCC variants, including signet-ring BCC and granular cell BCC, are discussed. Less commonly appreciated basaloid simulants, including ameloblastoma, cloacogenic carcinoma, and mucinous carcinoma, are described. Distinguishing among these variants and simulants of BCC is important because treatment and prognosis of each may vary. PMID- 1885826 TI - Prolongation of anesthesia in Mohs micrographic surgery with 2% lidocaine jelly. AB - The authors performed a prospective, randomized trial of topical 2% lidocaine jelly in patients with basal cell or squamous cell carcinomas to test the effectiveness of the jelly in prolonging the time of anesthesia between the multiple stages of Mohs micrographic surgery. There was a 48% increase in the duration of anesthesia achieved by the use of 2% lidocaine jelly in patients given 1% lidocaine with epinephrine. In patients given 1% lidocaine without epinephrine, there was approximately a 2.5 times greater duration of anesthesia achieved by using topical 2% lidocaine jelly. PMID- 1885827 TI - Localization of endogenous beta-galactoside-binding lectin as a means to distinguish malignant from benign skin tissue. AB - The immunolocalization of a 30-kd endogenous lectin, referred to as galaptin, was studied in various skin tumor types. Basal cell carcinomas expressed little or no galaptin, whereas nonmalignant basaloid cells, squamous cell carcinomas, melanoma, nevi, and stroma showed more prominent galaptin immunostaining. Therefore, the immunodetection of galaptin may aid the dermatopathologist in difficult histologic diagnosis. PMID- 1885828 TI - Clear cell squamous cell carcinoma. A histologic, immunohistologic, and ultrastructural study. AB - Squamous cell carcinomas (SCCs) usually show a standard histopathologic picture only varying with regard to their degree of differentiation. The authors describe a case of clear cell SCC that was studied by light and electron microscopy. The clear cells showed an empty cytoplasm that was periodic acid-Schiff and alcian blue negative. By electron microscopy these cytoplasms consisted of empty spaces and were not surrounded by membranes, which would be consistent with lipid vacuoles. The differential diagnosis of this uncommon variant of SCC requires consideration of other clear cell tumors. PMID- 1885829 TI - Growth of human basal cell carcinomas transplanted to C57/Balb/C bgJ/bgJ nu/nu (beige-nude) mice. AB - The purpose of this study was to measure growth parameters of transplanted basal cell carcinoma (BCC) to beige-nude mice during a 4-month observation time. Forty male beige-nude mice were transplanted with human BCC with our reported subcutaneous implantation technique. Initial volume and wet weight were determined for each tumor. The tumors were measured every 2 weeks by calipers with a final volume determined at 120 days, at which time the tumors were harvested, weighed, and processed for routine histology. Thirty-two tumor sites were positive for persistent tumor at harvest. Tumor volumes declined by an average of 51% and average tumor weight by 33%. There were increased numbers of mast cells surrounding the BCC tumor lobules. These results indicate that BCC can survive for 120 days in the beige-nude mouse. PMID- 1885830 TI - Clinical comparison of polyglactic acid (Vicryl) and polytrimethylene carbonate (Maxon) suture material. AB - Over a 1-year period, 584 repairs of surgical defects were completed using two different synthetic absorbable sutures, polyglactic acid (Vicryl) and polytrimethylene carbonate (Maxon). No difference in scar width or postoperative complications were found between the two sutures, but polytrimethylene carbonate (Maxon) demonstrated preferable handling and tying characteristics. PMID- 1885831 TI - Adjuncts to scalp reduction surgery. Intraoperative tissue expanders and hyaluronidase. AB - Scalp reduction has become an important part of the cosmetic surgeon's armamentarium in the treatment of male pattern alopecia. Recently, the use of two stage tissue expansion has been advocated for scalp reduction. Intraoperative tissue expansion obviates many of the disadvantages of delayed expansion and increases the yield of excised scalp by 20-30% over standard reduction techniques in the 20 patients studied. The addition of hyaluronidase to the local anesthetic facilitates its diffusion, enhancing anesthesia and the ease of dissection. Therefore, the use of intraoperative tissue expansion and the addition of hyaluronidase to the local anesthetic are two separate adjuncts to scalp reduction surgery. PMID- 1885832 TI - Diagnostic and therapeutic nail surgery. AB - The function of the nail unit is as a protective covering over the dorsal distal end of the digit. Some basic disease processes affecting the nail unit and the surgical techniques used for diagnosis and treatment are reviewed. PMID- 1885833 TI - Current issues in the performance of Mohs micrographic surgery. AB - Recently, a survey was sent to all members of the American College of Mohs Micrographic Surgery and Cutaneous Oncology concerning their performance of Mohs micrographic surgery. Responses to numerous questions regarding the daily practice of this technique revealed that many useful modifications have evolved over the years that serve to enhance the efficacy and the efficiency of the original Mohs surgical procedure. The results of this survey are presented and discussed. PMID- 1885834 TI - About the 5-year fibrel study. PMID- 1885835 TI - Management of the parotid gland and facial nerve in deeply invasive skin tumors. PMID- 1885836 TI - Re: Foam-rubber stents for skin grafts. J Dermatol Surg Oncol 1990;16:851-4. PMID- 1885838 TI - The glass slide curette. PMID- 1885837 TI - Re: Slit grafting: the use of serrated island grafts in male and female-pattern alopecia. J Dermatol Surg Oncol 1991;17:243-53. PMID- 1885839 TI - One of the ancillary procedures of "the face lift and ancillary procedures". PMID- 1885840 TI - Determining the mode of inheritance of pesticide resistance with backcross experiments. AB - The most widely used method for evaluating the mode of inheritance of pesticide resistance is based on bioassays of individuals from a backcross between F1 (hybrid of resistant and susceptible strains) and parental resistant or susceptible strains. Monte Carlo simulations of the standard backcross method showed that the probability of incorrectly rejecting the null hypothesis of monogenic inheritance (Type I error) was generally more than double the conventional value of P = 0.05. Conversely, the null hypothesis of monogenic inheritance was likely to be accepted in a relatively large proportion of cases in which resistance is controlled by two or more loci. Expected differences in mortality of backcross offspring between monogenic and additive polygenic models approached zero as dose approached extremely low values, extremely high values, and the LD50 of the backcross generation. Thus, the effectiveness of the backcross method depended strongly on dose. The power of the standard backcross method to correctly reject the null hypothesis of monogenic inheritance increased as number of loci, slope of parental dose-mortality lines, magnitude of resistance, and sample size increased. Guidelines for improving the design and interpretation of backcross experiments are presented. PMID- 1885841 TI - Horn fly (Diptera: Muscidae) insecticide resistance in Kentucky and Arkansas. AB - The effect of previous insecticide use patterns for horn fly control on the susceptibility spectrum of horn fly (Haematobia irritans [L.]) populations from Kentucky and Arkansas is described. Populations of horn flies from both states were tested with three pyrethroids (cyhalothrin, cypermethrin, and permethrin), three organophosphates (diazinon, pirimiphos methyl, and tetrachlorvinphos), and a chlorinated hydrocarbon (methoxychlor). Dose-mortality data indicated insecticide resistance in Arkansas and Kentucky. Two permethrin-resistant horn fly populations in Kentucky that did not have a history of exposure to methoxychlor were cross-resistant to this chlorinated hydrocarbon. Horn fly populations from both states with a history of at least three consecutive years of exposure to various pyrethroid ear tags were subsequently exposed to cattle tagged with cyhalothrin-impregnated ear tags for 15-16 wk. Such exposure resulted in a decrease in susceptibility to this pyrethroid (ranging from approximately 30 to greater than 100-fold) when compared with levels before treatment. Horn fly populations from Arkansas resistant to cyhalothrin (as a result of exposure to cyhalothrin ear tags) were cross-resistant to pirimiphos methyl. Seasonal exposure of an Arkansas and Kentucky horn fly population to cattle with ear tags impregnated with pirimiphos methyl resulted in a significant decrease in susceptibility to this organophosphate. PMID- 1885842 TI - Comparative toxicity of seven insecticides to immature stages of Musca domestica (Diptera: Muscidae) and two of its important biological control agents, Muscidifurax raptor and Spalangia cameroni (Hymenoptera: Pteromalidae). AB - The toxicity of seven insecticides was evaluated against unparasitized Musca domestica L. pupae and pupae parasitized by Muscidifurax raptor Girault & Sanders or Spalangia cameroni Perkins, two important biological control agents. Only pyrethrins + piperonyl butoxide (Pyrenone) was less toxic to M. raptor compared with house flies. Conversely, all of the insecticides except crotoxyphos were less toxic to S. cameroni compared with house flies. A plateau in the tetrachlorvinphos bioassay line for S. cameroni suggested that this colony had approximately 45% resistant individuals. The selectivity observed between immature stages of house flies and M. raptor or S. cameroni is different from that reported against adult stages of these same species, suggesting that selectivity of an insecticide varies considerably between different life stages. PMID- 1885843 TI - Red imported fire ant (Hymenoptera: Formicidae) control with a corn grit bait of fenoxycarb without soybean oil. AB - The standard fenoxycarb fire ant bait formulation (Logic), composed of pregel defatted corn grits and soybean oil toxicant, was modified by eliminating the soybean oil. This formulation without soybean oil contained greater than 2 times more fenoxycarb and was as effective as the standard bait formulation against laboratory colonies of red imported fire ant, Solenopsis invicta Buren. In field tests, the modified and standard baits were equally effective in controlling fire ants after 6, 12, and 18 wk. Individual worker ants obtained from plots treated with fenoxycarb baits without soybean oil had greater than 47 times less fenoxycarb than did workers from the plots treated with the standard fenoxycarb baits containing soybean oil. PMID- 1885844 TI - Distribution and density of polygyne fire ants (Hymenoptera: Formicidae) in Texas. AB - Multiple-queen or "polygyne" Solenopsis invicta Buren colonies are a serious economic and environmental concern because they occur in much higher densities than the monogyne form. Polygyne colonies have been found at numerous locations in the United States; nevertheless, the frequency and distribution of this form are poorly known. Almost 700 roadside sites in 168 Texas counties were surveyed. Polygyny was discovered at 54% of the infested sites. Polygyne populations were scattered in a mosaic across Texas. The frequency of polygyny varied somewhat with geographic region, but the pattern was generally unrelated to habitat and environmental conditions. Polygyne sites averaged more than twice as many mounds per hectare as monogyne sites. Populations of monogyne and polygyne forms were slightly lower in cooler and drier portions of the state. Mounds of both forms were about the same size. Polygyny was correlated with lower rates of sexual production and reduced numbers of native ants. The high frequency of polygyny in Texas indicates that the fire ant problem in the state is much greater than previously realized. PMID- 1885845 TI - Incorporation of pyriproxyfen in a German cockroach (Dictyoptera: Blattellidae) management program. AB - Pyriproxyfen (Nylar), a juvenile hormone analog (JHA), and acephate were used in a German cockroach, Blattella germanica (L.), management program. Monthly applications of acephate for 6 mo reduced nightly trap catches from 24.68-25.25 to 4.46-5.31 at 2 mo, and trap catches averaged 1.49-8.04 from 2-6 mo. After acephate applications were discontinued, trap catches increased from 6.86 at 7 mo to 28.08 at 12 mo. Pyriproxyfen was applied at months 0, 3, and 6. Monthly pyriproxyfen treatments were applied from 7 to 11 mo because, at month 6, only 21.00-27.30% of adults had wing twisting (one effect of pyriproxyfen exposure). These monthly applications resulted in 74.55-78.53% of adults with twisted wings in the German cockroach population at 12 mo. Trap catches in apartments treated with pyriproxyfen aerosol were significantly lower at 7, 8, 10, and 12 mo after the initial treatment than those that did not receive JHA treatment. At 7-12 mo, the pyriproxyfen residual spray did not significantly reduce German cockroach populations, but trap catches were consistently lower. German cockroach populations were sampled for 1 yr (from 13 to 24 mo) after pyriproxyfen applications were discontinued. Compared with those in apartments treated with acephate, trap catches in apartments treated with pyriproxyfen were significantly reduced from 12 to 18 mo after the initial treatment. At 18-24 mo, trap catches in apartments treated with pyriproxyfen aerosol were consistently lower than those treated with acephate, but these differences were not significant. PMID- 1885846 TI - Separation of cat flea (Siphonaptera: Pulicidae) instars by individual rearing and head width measurements. AB - Two methods to verify whether head width measurements fit Dyar's rule were evaluated for the separation of instars of the cat flea, Ctenocephalides felis (Bouche). Individual rearing was a reliable method of determining larval instar but was labor-intensive. The mean observed head widths were significantly different for each instar (first instar, 0.164 mm; second instar, 0.201 mm; third instar, 0.260 mm) and showed no sexual dimorphism. Head capsule width increased roughly 25% from instar to instar with geometrically progressing growth in accordance with Dyar's rule. However, head capsule width cannot be used to determine the instar of randomly selected larvae because the measurements overlap broadly between instars. PMID- 1885847 TI - Gelled diet for screwworm (Diptera: Calliphoridae) mass production. AB - A rearing system based on a diet gelled with Water-Lock G-400, a synthetic superabsorbent (poly(2-propenamide-co-2-propenoic acid, sodium salt)) (WL), was compared with the standard rearing system (liquid diet suspended in acetate fibers) for the mass production of screwworms, Cochliomyia hominivorax (Coquerel). The WL rearing system yielded 2% heavier pupae, 32% higher egg to pupa survival, and required 54% less diet and 88% less labor than the standard rearing system. Other advantages of the WL system include reduced susceptibility to suboptimal environmental conditions and labor practices and characteristics conducive to centralization and mechanization of rearing procedures. PMID- 1885848 TI - Lyme borreliosis--a review and present situation in Japan. AB - The skin diseases Erythema (chronicum) migrans (ECM, EM), Lymphadenosis benigna cutis (LABC), and Acrodermatitis chronica atrophicans (ACA) have long been described in northern Europe, and dermatologists are very familiar with these manifestations, which have been successfully treated with penicillin for about 40 years without the causative agent being known. Certain neurologic symptoms could be linked to tickbites during the 1920's and later also to EM. In 1977, Steere et al. reported a new form of inflammatory arthritis, mainly in school children in the community of Lyme, Connecticut, U.S.A., which they could also associate with preceding erythema and tickbites. Five years later, Burgdorfer was able to isolate Borrelia spirochetes from Ixodes ticks, which are known to be vectors of Lyme disease as well as of EM and ACA. The following year, Borrelia spirochetes were also isolated from Ixodes ticks and from skin lesions of patients in Sweden and Germany. These findings resulted in a large number of reports of new discoveries related to this infection, which is now known under the names of tick borne or Lyme borreliosis and, in the U.S., also as Lyme disease or Lyme arthritis. It has proven to be a great imitator disease, mainly through its involvement of the neurological system, and to be far more widespread than previously thought. The full course of the disease is not yet known, however it is clinically, like another spirochetosis, syphilis, divided into early and late stages. Manifestations involve mainly the skin, the joints, the nervous system (Neuroborreliosis), and the heart. Antibiotic treatment is effective, especially in the early stages. Like syphilis, the disease can be self-healing without treatment. People who are exposed to ticks should be aware of the risk of contracting this disease, also in Japan where Ixodes ticks have been shown to be carriers of Borrelia spirochetes. Cases, particularly of EM, but also with neurological symptoms, have already been diagnosed in Hokkaido, Honshu, Shikoku, and Kyushu. As Lyme borreliosis is now proven to exist in Japan, it is beneficial for dermatologists to know about the various presentations of this disease. This paper will briefly summarize the historical background, the clinical stages, the diagnosis, and the treatment of Lyme borreliosis, with a summary of the present situation in Japan. PMID- 1885849 TI - Towards a better understanding of cellular events in Mycosis fungoides: an immunohistochemical study. AB - In the present work, we have attempted to pay special attention to epidermal and dermal cellular events in Mycosis fungoides (MF). In the epidermis, the two dendritic cell populations, CD1+ and OKM5+, HLe-1+, the adhesion molecules OKM5 and DR on the surface of epidermal cells (Ecs), and cytoskeletal proteins were studied. CD1+ dendritic epidermal cells were generally more abundant than OKM5+, HLe-1+ ones with no interrelationship in their presence. OKM5+, HLe-1+ dendritic cells prevailed in the second stage plaques. The staining pattern with anti spectrin polyclonal antibody gradually presented increased intensity from Pre-MF to tumor stage. The activation-proliferation related immunophenotype was also examined, as well as other useful markers, in an attempt to correlate their presence in different stages of MF. Special emphasis was given to the staining pattern with the epidermal growth factor receptor (EGF-R) monoclonal antibody against three targets: epidermal, endothelial, and lymphoid cells. The presence of Ki-67 proliferation marker in suprabasal epidermal layers and lymphoid cells in the dermal infiltrate was also of interest. PMID- 1885850 TI - A case of erythromelanosis follicularis faciei with a unique distribution. AB - A 16-year-old Japanese boy with erythromelanosis follicularis faciei (EFF) with an unusual distribution is described. The clinical features of classic EFF consist of reddish-brown discoloration of the skin with fine follicular hyperkeratosis in the preauricular areas, and occasionally on the temples and the lateral aspects of the neck. The present case is unique in that similar lesions also occurred on the auricles and eyebrows. Both light and electron microscopic findings of the lesions were consistent with the diagnosis of EFF. PMID- 1885851 TI - Persistent facial ulcerations with a unique clinical appearance: possible trigeminal trophic syndrome. AB - We reported a 53-year-old woman with a persistent facial ulcer which moved gradually from the right marginal portion of the nasal root to the right lateral canthus along the margin of the right lower eyelid. The ulcer healed spontaneously. A similar ulcer developed at the entrance of the right anterior naris. The clinical findings were suggestive of squamous cell carcinoma, deep mycosis, mycobacterial infection, or a related condition. However, no definitive diagnosis could be made from the clinicopathological findings or the laboratory examinations, including bacterial, mycobacterial, and fungal cultures. The characteristic location of the lesion, and course of the disease, however, suggested the diagnosis of trigeminal trophic syndrome. PMID- 1885852 TI - A case of pemphigus vulgaris in a six-year-old girl. AB - A case of pemphigus vulgaris in a six-year-old Japanese girl is presented. She first developed vesicles and ulcerations in oral and laryngeal mucous membranes, showing a hoarse voice and fits of coughing with excessive slavering. She had skin blisters six months later. Biopsy of the skin lesion demonstrated the intraepidermal blister in a suprabasal location. Direct immunofluorescence (IF) of the skin lesion revealed deposits of IgG and C3. Indirect IF showed serum anti ICS antibody titer at 1:640. She was diagnosed as having pemphigus vulgaris. Treatment with oral prednisolone (1 mg/kg) proved effective. This is the first case of infantile pemphigus vulgaris in Japan. PMID- 1885853 TI - Discordant expression of tuberous sclerosis in monozygotic twins. AB - A set of 20-year-old female Japanese twins, most probably monozygotic, had clinical evidence of tuberous sclerosis (TS). They were discordant for symptoms. One of the twins exhibited facial red-brown papules (adenoma sebaceum), a dorsal shagreen patch, intracerebral calcifications, angiomyolipoma in the right kidney, and hypopigmented macules; the other had only a few hypopigmented macules. Modification of TS gene expression by the effects of environmental (extrinsic) factors is suggested. PMID- 1885854 TI - Characterization of circulating lymphocytes by monoclonal antibodies in donovanosis. AB - In 65 donovanosis patients, 53 ulcerogranulomatous, 10 hypertrophic, and 2 sclerotic, the hematological profile and quantitation of circulating blood lymphocyte subpopulations were studied with monoclonal antibodies and an indirect immunofluorescence technique to assess the immunological under-currents of the disease. The ulcerogranulomatous variant had increases in both total leucocyte and absolute lymphocyte counts. Total T-lymphocytes, CD4, CD8, CD22, and CD4/CD8 ratio were all significantly elevated. The hypertrophic variant, in contrast, showed a significant elevation only in the CD4/CD8 ratio. PMID- 1885855 TI - Self-induced vomiting in college women: its relation to eating, alcohol use, and Greek life. PMID- 1885856 TI - Simply irresistible! Marketing health to the student consumer. PMID- 1885857 TI - Gender, knowledge about AIDS, reported behavioral change, and the sexual behavior of college students. AB - This article reports on an analysis of the relationships among knowledge about AIDS, self-reported changes in sexual behavior, and independent measures of those behaviors--condom use, coital frequency, and number of partners. The sample consisted of 195 sexually active, heterosexual college students attending a northeastern state university in spring 1988. With other relevant variables held constant, statistically significant associations in the predicted direction were found between knowledge and reported change and each of the dependent variables among the men, especially the men not involved in relationships. Among women, however, the only significant association was that between reporting the beginning of condom use and the frequency with which condoms were used in the past year. Possible reasons for these gender differences are discussed. PMID- 1885858 TI - Fever response in elderly nursing home residents: are the older truly colder? AB - OBJECTIVE: To test the hypothesis that many nursing home residents with an apparently blunted fever response (maximum temperature less than 101 degrees F) may actually have a significant change in temperature (delta T greater than or equal to 2.4 degrees F) which is not recognized because of a low baseline temperature. DESIGN: Retrospective chart review for cases of infection that met specific criteria and for chart-recorded baseline and infection temperatures. Chart-recorded baseline temperatures were prospectively compared with re measurement of morning temperatures. SETTING: Nursing Home Care Unit of the VAMC West Los Angeles. PATIENTS: Random review of 40 residents' charts resulted in the detection of 69 infections among 26 residents over a 20-month period. Fifty randomly selected residents prospectively underwent comparison of chart determined and actual re-measurement of baseline temperatures. RESULTS: In 50 randomly selected residents, the mean oral baseline temperature of 97.4 +/- 0.2 (degrees F +/- SEM) closely approximated the mean nurse-recorded measures in the charts (97.6 +/- 0.1). Chart review detected 69 infections among 26 residents, with 53 episodes having a temperature recorded during the infection. The mean maximum temperature (Tmax) during an infection was 101.3 +/- 0.3 (degrees F +/- SEM) but 47% (25/53) of the episodes had a "blunted" fever response (Tmax less than 101 degrees F). Of the 25 "blunted" fevers (Tmax less than 101 degrees F), about one-fourth demonstrated an adequate change in temperature from baseline (delta T greater than or equal to 2.4 degrees F) but failed to reach 101 degrees F because of a low baseline. Most infections (89%) had a Tmax greater than 99 degrees F. CONCLUSION: Establishing a nursing home patient's basal temperature and monitoring for changes in temperature (delta T greater than 2.4 degrees F) and/or lowering the threshold for recognition of fevers (to 99 degrees or 100 degrees F) in nursing home residents with a change in function should assist in early recognition of infections. PMID- 1885859 TI - The relation of dizziness to functional decline. AB - OBJECTIVE: to assess the effect of dizziness on the probability that an older person will die or become functionally disabled within 2 years. Dizziness is a common symptom for which the prognosis is uncertain. This report compares the prognoses for dizzy and not-dizzy older people in order to assist clinicians who diagnose and treat these patients. DESIGN: a prospective study of a representative sample of elderly (70+) non-institutionalized Americans. Elderly subjects (n = 3,798) in the Longitudinal Study of Aging (LSOA) were asked questions about the presence of dizziness, medical conditions, and functional disability in 1984. The cohort was reinterviewed about functional disability in 1986. OUTCOME MEASURE: transition from functional ability to disability after 2 years. RESULTS: Bivariate analyses showed that dizziness predicts functional decline but not mortality. Multivariate models revealed that age, race, sensory impairment, vascular disease, and other morbidity are independent predictors of becoming disabled. Controlling for these potential confounders, dizziness does not predict an increased probability of becoming disabled. CONCLUSION: Elderly people who are dizzy should be evaluated for the presence of these related conditions. PMID- 1885860 TI - Predictors of mortality in older patients following medical intensive care: the importance of functional status. AB - OBJECTIVE: We examined predictors of hospital and 6-month mortality in older Medical Intensive Care Unit (MICU) patients with particular attention to age and functional status. Age is generally thought to be strongly associated with intensive care outcomes, but this relationship may be confounded by age-related changes. These age-related changes may be approximated by changes in functional status (FS). DESIGN: We conducted a retrospective chart review and collected severity of illness data using the Acute Physiology Score (APS), pre hospitalization FS dichotomized as limited or not limited, and hospital mortality. County death records were reviewed for 6-month mortality. SETTING: Three community hospital MICUs. PATIENTS: Four-hundred MICU patients aged 50 and older admitted during the study period. RESULTS: Limited FS was found in 42% of the 227 patients who had FS data in the chart. Mortality was significantly associated with APS, age, FS, immunocompromise state, comorbidity, and nursing home residence. In logistic regression analyses, while controlling for important variables, APS (P less than 0.001) and age greater than or equal to 75 with limited FS (P less than 0.05) were associated with hospital mortality. Six-month mortality predictors were APS (P less than 0.001), hospital (P less than 0.05), immunocompromised state (P less than 0.05) and age greater than or equal to 75 with limited FS (P less than 0.05). CONCLUSIONS: We found that among patients without functional limitations, the oldest group was no more likely to die than the youngest group. Age and functional status had a significant interaction: patients older than 75 years with functional limitations were almost six times more likely to die in hospital compared to the reference group of patients between 50-64 years old without functional limitations. We conclude that functional status is an important predictor of outcome in older MICU patients. PMID- 1885861 TI - Nursing home resources and tranquilizer use among the institutionalized elderly. AB - OBJECTIVE: To examine the relationship between selected resident and facility characteristics and the frequency and quality of tranquilizer prescribing and use in skilled nursing facilities. DESIGN: Retrospective review of medication profiles and pharmacy billing records using standardized protocol. SETTINGS: Seven skilled nursing facilities. PARTICIPANTS: All residents aged 65 years or older were eligible. Consent was given by 760 residents or guardians. Six refused permission. OUTCOME MEASURES: Drug use measures included the presence or absence of a tranquilizer order, any tranquilizer use during previous 30 days, and any deviation from selected drug use criteria. RESULTS: Of 760 residents, 38% had an order for an antipsychotic or antianxiety agent, and 28% actually received a tranquilizer. Comparing tranquilizer practices with specific drug-use criteria showed that nearly 19% of all elderly residents were exposed to some type of excess use such as long duration, polymedicine, or therapeutic duplication. Residents in facilities with less adequate staffing and other resources were significantly more likely to have a tranquilizer order, to have a tranquilizer administered, and to have any deviation from drug-use criteria. The data also show higher rates of deviation from criteria among residents with a diagnosed mental disorder, younger residents, and Medicaid recipients. CONCLUSION: More attention must be paid to environmental factors that may undermine current efforts to improve psychotropic drug prescribing and use in skilled nursing facilities. PMID- 1885862 TI - Effect of education on the mini-mental state examination as a screening test for dementia. AB - We studied whether Mini-Mental State Examination (MMSE) norms for detecting dementia in elderly outpatients vary according to educational attainment. Subjects were 109 elderly outpatients with Alzheimer's dementia and 100 non demented outpatient controls. Receiver operating characteristics (ROC) of the MMSE were examined among three strata of educational attainment: middle school, high school, and college/graduate school. MMSE ROC curve areas were .95-.96 in the three educational strata. Assuming a dementia prevalence of 10%-30%, the most accurate lower limits of normal for MMSE scores and their attendant sensitivities and specificities were 21 for middle school (.82/.94), 23 for high school (.79/.97), and 24 for college/graduate school (.83/1.00) attainment. These norms accurately classified over 90% of subjects in all three educational strata. We conclude that education-specific norms optimize performance of the MMSE as a screening test for Alzheimer's dementia in elderly outpatients. PMID- 1885863 TI - Major depressive disorder in hospitalized medically ill patients: an examination of young and elderly male veterans. AB - OBJECTIVE: To study the epidemiology of depressive disorder in younger and older medical inpatients. DESIGN, PATIENTS, & SETTING: Depressive disorders were examined using the Diagnostic Interview Schedule in 116 young and 332 elderly medically ill men hospitalized in a VA medical center. RESULTS: Major depressive disorder was diagnosed in 22.4% of men under 40 and 13.3% of those age 70 or over; minor depression was found in 18.1% of young and 29.2% of older men. Besides age, other risk factors for major depression were impaired social support, severe medical illness or functional disability in older men, and history of psychiatric problems primarily in younger men; specific medical diagnosis was not a risk factor. Major depression was associated with more severe symptomatology in younger patients; in both age groups, however, symptoms were of prolonged duration and frequently included suicidal thoughts. CONCLUSIONS: Depressive disorder in hospitalized male veterans is common, varies with age, severity of medical illness, degree of social support, and history of psychiatric problems and is associated with considerable psychological morbidity. PMID- 1885864 TI - Detectable serum levels of tumor necrosis factor alpha may predict early mortality in elderly institutionalized patients. AB - OBJECTIVE: To determine if detectable serum tumor necrosis factor alpha (TNF) levels are associated with higher mortality in nursing home residents. SUBJECTS AND METHODS: The basal serum concentrations of TNF and interleukin-1 alpha (IL-1) were measured in 129 elderly nursing home patients (mean age of 89 years), and survival in the cohort was monitored over a 13-month period. RESULTS: At 4 months follow-up, seven out of 33 patients with detectable serum TNF levels had died (21.2%), and only three out of 96 patients with undetectable serum TNF levels had died (3.1%) (P less than 0.001). The difference in mortality remained significant up to 13 months of follow-up (P less than 0.05). Those with detectable serum TNF levels and those with undetectable levels were comparable in age, body mass index, hematocrit, lymphocyte counts, and serum level of albumin, prealbumin, and retinol-binding protein. When patients with detectable serum IL-1 levels were compared to those with undetectable levels, there were no significant differences in mortality over a 13-month period. CONCLUSION: Detectable serum TNF levels in elderly nursing home patients may be a predictor of early mortality. PMID- 1885865 TI - The ethics of pressure sore prevention and treatment in the elderly: a practical approach. AB - The management of pressure sores in elderly patients raises a number of ethical dilemmas for health care professionals. Aggressive treatment of advanced pressure sores is often inconsistent with the overall goals of therapy. Private and public funding for effective prevention and early treatment are restricted and constrained. Little information is available that proves treatment efficacy. Health care professionals and their institutions are often stigmatized by the occurrence of a pressure sore even though accountabilities may lie in the natural history of the disease. We use case analysis to identify ethical dilemmas in pressure sore prevention and management and suggest a framework for ethical decisionmaking so that health care professionals and public policy analysts can make informed judgments about patients and standards of quality care. PMID- 1885866 TI - Acute delirium associated with ciprofloxacin administration in a hospitalized elderly patient. PMID- 1885867 TI - Senescence-accelerated mouse (SAM): a novel murine model of accelerated senescence. PMID- 1885868 TI - Medicare reimbursement for geriatric assessment: report of the American Geriatrics Society Ad Hoc Committee on Geriatrics Assessment. AB - This ad hoc committee report from the American Geriatrics Society proposes the prompt initiation of Medicare reimbursement for geriatric assessment (GA) services (also termed comprehensive geriatric assessment or geriatric evaluation and management services). Despite an extensive body of literature documenting the effectiveness of GA for improving health care outcomes in many settings for identifiable groups of frail elderly patients, no explicit Medicare reimbursement mechanisms currently exist to cover GA services provided by either hospital or physician. We believe that new physician reimbursement codes specific for geriatric assessment should be established in the Current Procedural Technology (CPT-4) manual and that reimbursement for GA should be specifically provided under Part B of Medicare. Further, we believe that hospital reimbursement within the Medicare prospective payment system should be modified to encourage GA during inpatient stays for appropriate patients. This paper summarizes the background for these recommendations. It defines the major content of GA at three levels of intensity--screening, intermediate, and comprehensive. It describes the major sites for conducting GA--hospital, office, home, nursing home. Finally, it proposes criteria for targeting patients most likely to benefit from GA. PMID- 1885869 TI - On the importance of longitudinal research in Alzheimer's disease. PMID- 1885870 TI - OBRA regulations. PMID- 1885871 TI - To float a Swan-Ganz or not? PMID- 1885872 TI - Foot problems in older patients. PMID- 1885873 TI - Geriatric evaluation and management units: experimental methods for evaluating efficacy. AB - A multi-site randomized controlled trial could most conclusively establish the efficacy of geriatric evaluation and management units, but many questions must be answered to design such a trial. First, the research questions needs to be rigorously specified. This will facilitate decisions concerning the types of patients to be included in the study. Second, the intervention requires a clear definition, including its component parts, to improve replication across multiple sites. Third, the type of randomization (ie, by hospital or by patient) and the timing of randomization (ie, at admission or at some later point during care) need to be considered. Fourth, because this type of intervention cannot be administered in a blind fashion, bias is a critical concern. Outcome measures must be selected carefully so that those least susceptible to bias are given the highest priority. Despite the need to address all of these questions, the time is upon us to conduct a multi-site trial of geriatric evaluation and management programs. PMID- 1885874 TI - Geriatric evaluation and management: current status and future research directions. AB - In the last decade the concept of geriatric evaluation and management (GEM) has been widely discussed in the literature. Studies of GEM have occurred primarily in three settings: inpatient units, outpatient clinics, and specialized types of home care. We have reviewed the literature, focusing on randomized trials, to determine the strength of the evidence for the efficacy of these interventions. Two single-site randomized controlled trials of inpatient GEM units have been conducted and indicate that such units that provide care to targeted disabled older patients probably have a favorable impact on subsequent physical function, rates of institutionalization, and mortality. Two randomized trials of inpatient GEM consultation teams have been conducted. The trial that did not target high risk individuals showed no benefit while the trial that did target an at-risk group showed that those receiving the service had improvements in mental status and short-term mortality. The results of randomized trials of outpatient GEM clinics to date have been unimpressive. Two trials of in-home GEM by a trained observer tended to show that the service resulted in a reduction in mortality. To date randomized trials of GEM have been very heterogeneous in terms of the type of assessment and subsequent care, the site in which services are delivered, and the manner in which patients are selected for the studies. This limits the ability to compare and extrapolate across studies. In the future there is a need to better clarify the selection of study participants, the exact structure of the assessment intervention provided, and the elements of successful interventions that may be most critical to insuring a good outcome. PMID- 1885875 TI - Targeting strategies: an overview of criteria and outcomes. AB - Researchers generally agree that Geriatric Evaluation and Management (GEM) Units are effective only when they are targeted at a specific group of frail, elderly patients who are most likely to benefit. Such patients are those who are neither too sick (eg, severely demented or moribund) nor too well. Various strategies for identifying such patients have been employed by investigators with little consensus on the most efficient targeting criteria. Criteria most often use for inclusion in GEM programs are various combinations of patient age, degree of functional impairment, presence of geriatric conditions (eg falls, incontinence, confusion), particular diagnostic conditions (eg, multiple disorders), and psychosocial conditions (eg, living alone, recent bereavement, low income). Commonly used exclusion factors are severe dementia, inevitable nursing home placement, and terminal illness. Outcome studies suggest that beneficial effects of GEM care are most apparent when patients are selected using specific clinical criteria. Future research on targeting should address the potential need for differing criteria in different settings (eg, inpatient vs outpatient GEM units), simplifications of criteria for greatest ease of application, and prospective evaluation of which criteria best predict functional improvement, longer survival, and reduced health care expenditures in response to GEM care. PMID- 1885876 TI - Working group recommendations: targeting criteria for geriatric evaluation and management research. AB - To maximize the cost effectiveness of geriatric evaluation and management (GEM) programs, criteria need to be established for selecting patients most likely to benefit. A working group was convened to define appropriate patient selection (targeting) criteria for each type of GEM program and to consider research questions for future targeting studies. The group outlined targeting criteria for the spectrum of GEM program types and locations. GEM program types included: inpatient GEM units; hospital geriatric consultation service; GEM programs in nursing homes; outpatient GEM programs for functionally impaired persons; and geriatric community outreach/screening programs for functionally independent elders. For each program type, the group outlined targeting criteria based on current literature and experience. Because research has not yet established the effectiveness of many of these patient targeting strategies, the group drafted a set of research questions, pertinent to targeting, that require attention: (1) For each identifiable population of elderly people, who are most likely to benefit from GEM? (2) How should these people best be identified/targeted? (3) What criteria should be used for targeting? (4) How and how often should population screening be performed to identify persons in need of GEM? PMID- 1885877 TI - Working group recommendations: research on content and efficacy of geriatric evaluation and management interventions. AB - Methods of conducting comprehensive geriatric evaluation and management (GEM) are proliferating in a variety of clinical settings. However, rigorous evaluations of efficacy for this new approach to care of older patients have demonstrated a favorable impact on patient outcome in only a few studies. All of these have been controlled single site studies, and replication is needed. If replication studies show similar results, further studies should be undertaken to define the minimum necessary intervention to achieve the desired outcome. Controlled trials are needed to determine if consultative geriatric evaluation and/or primary patient management is effective. Further innovative work is needed in model development for geriatric assessment and management in outpatient settings. Finally, studies of geriatric evaluation and management in other environments, such as home care or the nursing home, are recommended. PMID- 1885878 TI - Working group recommendations: methods for geriatric evaluation and management research. AB - Methodological issues relating to multi-site studies of inpatient geriatric evaluation and management units were the focus of this working group's deliberations. The group favored a randomized clinical trial in which the inpatient geriatric evaluation and management unit was coupled with outpatient geriatric care. Inclusion of a broad spectrum of patients stratified according to risk for poor hospital outcomes was proposed in order to obtain information on the types of patients that would be most likely to benefit. The need for a detailed definition and description of care in the unit and of "usual care" was emphasized. Serious concerns were raised about including both VA medical centers and private hospitals in the same trial due to differences in the implementation of such a program. Furthermore, fears of contamination of the control group suggested that hospitals could be randomized either to provide usual care or have a GEM unit. However, this strategy would necessitate that hospitals that have already developed inpatient GEM units would be excluded from the trial and could be costly because of the number of hospitals that would be required. PMID- 1885880 TI - Research strategies for geriatric evaluation and management: conference summary and recommendations. AB - In this paper, we present the consensus statement from a national conference on research priorities and methodologies for studying geriatric evaluation and management (GEM) programs. These conclusions, discussion points, and recommendations resulted from discussions of plenary papers, working group deliberations, and a final session in which findings were synthesized by the conference co-chairmen and presented to conference participants for final review. Major conclusions included: (1) The importance of linking geriatric evaluation with care management in future studies; (2) The need for multi-center trials of inpatient units to establish efficacy; (3) The importance of studying criteria for targeting GEM care on patients who are most likely to benefit; (4) The need for further developmental studies of outpatient GEM clinics; (5) The importance of assessing a range of outcomes including mortality, patient function, satisfaction, caregiver burden, and cost; and (6) The need to define more carefully the nature of the intervention that is being studied to aid in comparing and extrapolating findings. The following research priorities for GEMS were formulated based on the conference: (1) Within the VA health care system, a multi-site randomized trial of inpatient GEM units should be initiated; (2) Multi site studies of inpatient GEM units and consultation teams linked to outpatient care should be initiated in non-VA settings; (3) Studies should identify the components of GEM that are most critical to outcome; (4) Studies should explore efficacy of GEM in settings that have not been well studied to date such as nursing homes; and (5) Studies are needed to test screening methods and targeting criteria for GEM in all settings. PMID- 1885879 TI - Working group recommendations: measuring outcomes of care in geriatric evaluation and management units. AB - Issues related to measuring outcomes of care in geriatric evaluation and management (GEM) units were identified by the outcomes working group of the GEM evaluation conference. GEM units have as a major goal the improvement or maintenance of both physical and psychosocial function. Suggested outcome measures for physical health included survival, restricted activity days, general health perceptions, comprehensive physical function, and miscellaneous specific types of functioning. In the area of psycho-social function, the working group suggested measuring cognitive function, affect/life satisfaction, social function, and satisfaction with care. The patient's caregiver (eg, spouse or child) is often an important target of GEM care, and the group suggested measuring caregiver burden, life satisfaction, and assessment of patient behavior problems. While the primary goal of GEM units is to improve health status, their effects on the utilization and cost of health care are important to decisions about wide-spread implementation and funding. The group therefore suggested a comprehensive assessment of these outcomes. Among the large array of recommended outcomes, the most important were thought to be mortality, function, and cost. PMID- 1885881 TI - [Pauline and Charlotte or reproduction in the year 2030]. PMID- 1885882 TI - [Applications in gynecology-obstetrics of the first legal cases concerning HIV transmission by blood transfusion and errors in screening]. AB - The intention of the authors in this paper is to provide a preliminary report on what is going on in order to inform gynaecologists and obstetricians of the initial legal steps concerning the transmission of HIV by blood transfusion and the defects in screening for the infection which could have been caught by a pregnant woman; where there was a possibility of a false-positive diagnosis from the serum which could have brought about a termination of pregnancy unnecessarily. Two decisions have been analysed, the one according to the old administrative law and the other according to the more recent judgement, involving pregnancy and other decisions which were not directly concerned with the specialty. These can be instructive for practitioners because these circumstance may come up again. It is worth looking at the case papers where medical responsibility can be invoked involving the professional insurance agencies. These cases will increase in numbers in the future. The authors analysed in the light of the decisions that had been made, possible penal, civil and administrative liabilities that could threaten gynaecologists and obstetricians in this field. The study ends by pointing out what can be done to lessen these medico-legal risks by avoiding blood loss in operations, by finding other ways than blood transfusions towards the end of pregnancy, but above all, by reducing and controlling the number of blood transfusions carefully. This has to be done in collaboration with the transfusion centres and the laboratories where the blood is tested. Judges will have to work out where the responsibility lies if the cases come before them. PMID- 1885883 TI - [Cystic hygroma of the neck. Antenatal diagnosis, prognostic factors, management. 42 cases]. AB - The authors report a series of 42 cases of cystic hygroma of the fetal neck diagnosed antenatally. Cystic hygroma is one of the signs suggestive of chromosomal or congenital abnormalities that occur very early and are very specific. A diagnosis can be made from the ninth week of amenorrhoea onwards by vaginal ultrasound. 73% of the karyotypes that were obtained were abnormal. The large majority (54% = have Turner's Syndrome, but there are some of the karyotypes that are normal. Our figures correspond with those in the literature. Several factors were analysed to show the influence of this pathology on the prognosis which is overall awful (only 11.5% of infants were born alive an only 7.5% survived). Factors for a good prognosis would be a normal karyotype and the spontaneous resolution of cystic hygroma in the second trimester of the pregnancy. Hydrops is a factor of poor prognosis and it occurs in 60% of cases of cystic hygroma but unfortunately 30% of cases where the karyotype is normal have severe malformations (bone, kidney and digestive tract). The resolution of the cystic hygroma in the second trimester of pregnancy does not exclude an abnormal karyotype or a severe congenital malformation associated with the condition. As cases do recur in the same family there is an indication that a suspicion that the condition can be an autosomic, recessive or even dominant condition. The authors advise that the diagnosis should be made early and thoroughly in order to carry out chorionic villus sampling to determine the karyotype early before the very important sign for abnormality disappears as it may. PMID- 1885884 TI - [Evaluation of the risks of transabdominal chorionic villus sampling. 600 cases]. AB - The authors report their experience with fine needle chorionic villus sampling carried out transabdominally. Six hundred antenatal karyotype diagnoses were made using this method. The indications were: maternal age: 509 (85%), previous chromosomal abnormalities: 57 (9.5%), parental chromosomal abnormalities: 19 (3%), X chromosome linked diseases: 9 (1.5%), others: 6 (1%). The patients were divided into two groups according as to whether the test was carried out before or after 12 weeks of amenorrhea (Group 1 and Group 2). Each group was divided into two sub-groups according to whether the amniotic membranes were broken or not. The test was carried out using a 20 gauge needle under ultrasound control with a to-and-fro movement using continuous aspiration. The success rate was 98.4%. Minor complications were rare. Contractions 9 (1.5%), spotting 4 (0.6%), small haematomas 13 (2.1%), loss of amniotic fluid 4 (0.6%). The level of unintentional abortions depended on the duration of the pregnancy and whether the amniotic cavity or not was entered. In group 1 (before or at 12 weak amenorrhea) there were 2 abortions out of 124 cases (1.6%) and if the needle entered the amniotic cavity 10 out of 57 cases (17.5%). In group 2 (after 12 weeks of amenorrhea) there was no ill effect from going into the amniotic cavity to the rest of the pregnancy. The abortion rates was 6 out of 419 (1.43%). There were no false positive or negative results.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1885885 TI - [A case of neurofibroma of the vagina. Review of the literature]. AB - Large tumours of the vagina are rare. If a vaginal neurofibroma is found a search should be made for other sites of Recklinghausen's disease. The tumour should be removed surgically to avoid risk of degeneration. PMID- 1885887 TI - [Cervico-vaginal cytology and condylomata. Reproducibility and predictive value]. AB - Human Papilloma Virus (HPV) is associated with two groups of intra-epithelial lesions of the cervix: the condyloma or the very low grade lesion, and intra epithelial cervical neoplasia (CIN) or a higher grade of lesion. Cervico-vaginal cytology can be used to screen for these two types of lesion. Further to this research is to evaluate the reproducibility and the predicted value of cervico vaginal cytology to detect condylomas. The study is based on 610 patients who were referred because of abnormal cytology. 270 (44%) of these patients were referred because the cytology suggested condylomas and 241 (40%) had cytological signs of CIN. The reference cytology and the control cytology did not accord well. Control cytology showed signs of condyloma in only 116 (43%) of the 270 patients referred for this type of lesion. On the other hand in the case of CIN there was better correlation. Of the 241 patients who were referred for cytological signs of CIN 185 (70%) also had these signs on controlled cytology. The positive predictive value of cytology to diagnose condyloma is relatively poor. In only 126 (47%) of the women referred with diagnosis of condyloma could this diagnosis be confirmed histologically, 20% of these 270 patients had CIN. In contrast the positive predictive value of cytology with signs of CIN were better 182 (76%) of 241 patients who were referred with CIN had the diagnosis confirmed histologically. PMID- 1885886 TI - [Colposcopy of the vulva]. AB - A detailed colposcopy study of the cervix, vagina and vulva was conducted in 365 women referred for genital human papillomavirus (HPV) lesions, abnormal cervico vaginal smear or cervical intraepithelial neoplasia (CIN). Valvuloscopic abnormalities, all biopsied, were found in 144 women, i.e. 40% of the population studied. Five types of vulvoscopic abnormalities are described: diffuse acidophilia (55% of abnormalities), acidophilic maculae (17%), micropapillae (20%), papulae (4%) and leucoparakeratosis (4%). Histological examination of the biopsy specimens obtained from 144 women with abnormal vulvoscopy showed 55 typical flat condylomas (38%), 50 probable flat condylomas (35%) and no signs of condyloma in 38 cases (27%). It also revealed the presence of four vulvar intraepithelial neoplasias (VIN) stages 2-3, all of them associated with typical or probable condyloma. Comparison between the 144 abnormal vulvoscopies and a series of 14 normal vulvoscopies made it possible to establish a significant correlation between the presence of valvuloscopic abnormalities and the finding of histological signs of typical or probable flat condyloma. The vulvoscopic images of subclinical vulvar HPV infection, but apart from papulae and, to a lesser extent, leucoparakeratosis, correlations between vulvoscopic and histological images were imprecise. PMID- 1885888 TI - [Spontaneous regression of flat condylomata of the cervix]. AB - In this study 146 patients with a human papilloma virus infection of the cervix detected on cervical smear. This infection was at the worst associated with CIN 1 or CIN 2. No treatment was carried out on these patients except for advising the use of condoms. Among the 123 women whose diagnosis was CIN 1, 65.2% of them had a negative smear within 18 months. This somewhat high rate of spontaneous regression was found in out patients who were not selected. They are near the results published by Brown in a similar study. The statistics drawn from hospital patients give lower regression rates; but these patients were selected by their doctors because they did not show regression on subsequent smears. It is therefore recommended that these patients should be assessed colposcopically and there should be a wait of 6-12 months before treating patients with CIN 1. PMID- 1885889 TI - [Endometrial resection for metrorrhagia: 45 cases]. AB - Treatment of metrorrhagia has recently been modified because of the use of the hysteroscope which allows two methods to be used: diathermy and endometrial ablation or laser destruction of the endometrium. This retrospective study of ablation of the endometrium was carried out on 45 cases: the patients had excessive bleeding or menorrhagia that had been developing and in an average about 18 months. The mean age of the patients was 48 years with a deviation of 7 years. More than half the women were overweight, a quarter weighing more than 80 kgs with a height of 1 metre 60. A third of the cases had pathology associated with the condition. In 24 cases endometrial resection was carried out by itself but in 21 cases endometrial resection was accompanied with removal of polyps or of submucous myomata. The results were: There was no anaesthetic complication or accident; The operation was complicated only once by perforation of a cornu; Bleeding stopped completely in 94% of cases with an average duration of follow-up of 7 1/2 months; Control hysterosalpingography showed synechiae in 70% of the cases; The histology showed a preponderance of mucosal hyperplasia and of small fibroids. The authors point out: that it is important to learn carefully the operative technique to lessen the risks of complications, but the clinical results compare with the best in the literature but with the price to pay of a high incidence of synechiae. The following questions will have to be answered in the future: What is the risk of cancer after endometrial ablation? Is it possible to avoid synechiae so that the whole cavity of the uterus can be assessed later? What is the role of medical as opposed to surgical treatment in heavy bleeding at the time of the menopause? PMID- 1885890 TI - [Resection under echographic control of septate uteri]. AB - Septate uterus can be responsible for such infertility as requires surgical treatment. This series of this kind of uterine malformation in 37 cases makes it possible to evaluate the efficacy of a new technique for correction of the septum. It has the merit of not requiring laparotomy and above all it avoids carrying out hysterotomy which definitely weakens the uterus. The technique assists in correcting the defect through the cervix with scissors under ultrasound control. The morphological results on the uterine cavity are perfect in 19 patients. In 12 patients there was an arcuate fundus left and in 5 cases the section was insufficient and required a repeat procedure. This brings up to 20 the number of perfect corrections and 16 the number left with an arcuate fundus. The simplicity results were assessed in infertile patients and show that the number of abortions per patient dropped from 1.72 on average to 0.38 thanks to the ultrasound correction that was carried out. The simplicity of this method which can be carried out on an outpatient basis makes it possible to spread the indications to a situation where the Bret-Palmer technique could not be carried out and in particular in cases where IVF was being considered. PMID- 1885891 TI - [The perinatal period and pediatric psychiatry. Reflections on the interworking of a maternity department]. AB - This work is an assessment of the results of routine meetings between a children's psychiatrist and mothers with their new born babies in a general district hospital's maternity department. The approach is to look for early detection of faults in the mother-child relationship. Difficulties can be grouped into simple categories. The presence of a paediatric psychiatrist in a maternity department has made it possible to show up the value of specialised help early on as much for the 25% of women who are distressed after delivery as for the 6-7% that are really worrying cases. PMID- 1885892 TI - [Periodic disease and pregnancy]. AB - The authors report a case of familial Mediterranean fever in a pregnant woman treated with Colchicine. She delivered normally at term. A review of the literature shows that colchicine does not have a teratogenic effect which it was long thought to have. All the same it is best to carry out fetal karyotype examination using early amniocentesis. Furthermore, colchicine improves fertility which is disturbed in these patients and pregnancy has a good effect on the disease. PMID- 1885893 TI - [Heart surgery with extracorporeal circulation during pregnancy. Review of the literature with a case history]. AB - The authors report a case of replacement of a mitral valve and of tricuspid annuloplasty using extracorporeal circulation in a pregnancy of 23 weeks amenorrhoea with a satisfactory result for the mother and the birth of a healthy baby after 35 weeks of amenorrhoea. A review of the literature made it possible to analyse the problems occurring in pregnancies in woman who have been fitted with a cardiac valve prosthesis and who have to have cardiac surgery in pregnancy. PMID- 1885894 TI - [Delivery of pregnant women in Zaire who have previously had cesareans. An analysis of 145 cases]. AB - A retrospective study was carried out to survey 145 women who gave birth who previously had caesarean operations, delivered in the Department of Gynecology and obstetrics of the University Clinic in Kinshasa between 1st January and 31st December 1981. The authors have analysed the obstetric outcome of these pregnant women. Their study gives rise to the following results: The incidence of women who had previously had caesarean operations was 2.4%. 92 women (63.4%) delivered normally and 53 (36.6%) had another Caesarean operation. Favourable factors leading to a normal delivery were previous vaginal delivery, particularly after a caesarean operation, and a vertex cephalic presentation. The growing number of Caesarean operations had led to many repeat operations. Long labour is one of the principal factors leading to ruptured uterus which did not seem to make the prognosis for the mother any worse. On the other hand fetal prognosis was saddled with an increased mortality rate (37.5%). Even this high figure is better than the prognosis in previous series: 50% in 1975 [24], and 46% in 1983 [26]. PMID- 1885895 TI - [Aplasia cutis after exposure to carbimazole in utero]. AB - The authors report a case of a skin defect in the scalp of a child whose mother took carbimazole during her pregnancy. Including our case there are now 15 congenital scalp defects reported: however, these rare cases do not show that carbimazole should not be used during pregnancy. PMID- 1885897 TI - [Feticidal band of the umbilical cord]. PMID- 1885896 TI - [Analysis of 1410 examinations of fetal pathology at the University Hospitals of Bordeaux]. AB - We present a retrospective study of 1,410 fetal pathological examinations performed in the department of pathology of the CHU de Bordeaux. Initially, the recruitment of the cases was limited to the three maternity units of the CHU. Public and private maternities and departments of pediatrics from the whole of Aquitaine (S.W. province) as well as a certain number of neighbouring provinces now send us their material for analysis. Fetal pathological examination is systematically indicated in cases concerning spontaneous abortion, pregnancies terminated after prenatal diagnosis and stillbirths. Autopsies performed on children aged from 0 to 1 year have been included. The same technique has been used for all examinations and the data have been recorded on a computerized system (Centre Regional d'Informatique Hospitaliere). Current data analysis for age at death, sex-ratio, maternal age, mode of abortion and pathological conditions are given. We found at least one pathological anomaly in 43.2% of the spontaneously aborted fetuses and stillbirths. Nevertheless, our aim is to demonstrate that foetopathology units can play a role not only for diagnoses having a significant impact on genetic counseling, but also as a database for epidemiological studies. PMID- 1885898 TI - Esophageal epithelial defense against acid injury. AB - The esophagus is lined with a stratified squamous epithelium. This epithelium, like that of stomach and duodenum, is able to resist damage even on continuous exposure to luminal acid. The intrinsic epithelial defenses against acid injury in the esophagus can be labeled "tissue resistance." Tissue resistance is not a single factor but a number of structural and functional elements within the epithelium that interact in a dynamic way to provide protection. This article enumerates the components of this epithelial defense system and describes their roles in the protective process. Furthermore, the ability of agents such as indomethacin and sucralfate to provide protection against acid injury to esophageal epithelium is discussed in light of their known actions at the tissue level. PMID- 1885899 TI - Clinical studies of sucralfate in reflux esophagitis. The European experience. AB - Reflux esophagitis is encountered quite frequently in clinical practice. Symptoms can be mild, moderate, or severe and complications can occur, particularly if the disorder is untreated or undertreated. Treatment is aimed at relieving symptoms, healing lesions, and preventing complications. Various pharmacologic options are available for treatment, including antacids, alginate/antacid compounds, acid reducing agents, prokinetic drugs, and agents that protect the mucosa. This article reviews a number of clinical studies evaluating sucralfate in the treatment of reflux esophagitis. Almost all of the investigations were conducted in Europe and encompassed open-label studies, placebo-controlled trials, and comparative studies. From the studies discussed, it can be concluded that sucralfate not only has a place in the treatment of peptic ulcer disease, but is also effective in treating reflux esophagitis. Sucralfate is comparable to H2 receptor antagonists in symptom improvement and healing rates. In addition, the studies reviewed have shown sucralfate to be safe and well tolerated. PMID- 1885900 TI - Mechanisms of gastric mucosal injury and protection. AB - This article emphasizes and reviews the premise that because the pathogenesis of acute gastric mucosal injury is multifactorial, several protective mechanisms should also be considered in analyzing gastric mucosal defense. The first part of the article reviews the pathogenesis of acute gastric mucosal injury by major etiologic factors such as hypoxia and chemical and biological agents, and emphasizes the common endogenous mediators of damage (e.g, endothelins, leukotrienes, thromboxane, platelet-activating factor, monoamines, free radicals, proteases, ammonia, hydrochloric acid, and bile acids--in decreasing potency). The second part of the review is devoted to the gastroprotective mechanisms that are analyzed by anatomical (histologic) location and biochemical processes. The endogenous mediators of acute gastroprotection include prostaglandins, sulfhydryl (SH) compounds, non-SH antioxidants, polyamines, and epidermal growth factor, whereas the protective and mediatory role of glucocorticoids, somatostatin, pentagastrin, histamine, gangliosides, and calcitonin gene-related peptide need further studies. A list of endogenous and exogenous chemicals that exert biphasic, damaging, and protective effects on the gastric mucosa in also included. The final common pathway of acute gastroprotection at the structural and functional level seems to be the preservation of subepithelial microvascular integrity leading to maintenance of mucosal blood flow that allows the energy dependent rapid restitution (cell migration) from surviving gastric neck cells to repair the superficial epithelial defect. Very new data on the contribution of a histodilutional barrier and release of proteases to gastroprotective processes are also discussed. PMID- 1885901 TI - The clinical significance and pathophysiology of stress-related gastric mucosal hemorrhage. AB - Critically ill patients admitted to intensive care units (ICUs) develop a spectrum of gastroduodenal mucosal lesions that may result in mucosal hemorrhage and subsequent morbidity and mortality. Although stress-related mucosal lesions may be detected endoscopically in most critically ill patients, the incidence of clinically significant bleeding from these lesions is difficult to establish because of the heterogeneity in patient populations, the definitions of bleeding, and the methods of monitoring in various studies. Bleeding occurs overall in approximately 16% of patients not receiving prophylaxis, but the incidence of life-threatening hemorrhage appears to be much lower (less than 6%). In light of the increasing use of pharmacologic prophylaxis in ICUs, the clinical impact of stress-related bleeding and its prophylaxis is discussed in terms of bleeding incidence, morbidity and mortality, cost, and potential side effects. The pathophysiology of stress-related mucosal ulceration involves the complex interaction of gastric luminal factors, alterations in blood flow and intramucosal pH, and alterations in numerous factors that are normally responsible for maintaining an intact mucosa. The pathophysiology of stress ulceration is discussed, with an emphasis on cause-and-effect relationships, evolving areas of investigation, and implications for prophylaxis and treatment. PMID- 1885902 TI - Non-acid mechanisms of gastric and duodenal ulcer formation. AB - The pathophysiology of gastric and duodenal ulcer disease has two sides: the aggressive attack, principally by the highly corrosive gastric acid; and the defending forces of mucus, mucosal resistance, and other protective substances and functions. This report reviews the roles of both the attacking and defending forces in the pathophysiology of ulcer disease. It also discusses how an early notion of ulcer formation (e.g., the Schwarz dictum of "no acid, no ulcer," first published in 1910) became the slogan by which ulcer disease was understood and from which therapy took its cue. Subsequent work has since found that the Schwarz dictum holds for duodenal ulcer, but not for gastric ulcer. Non-acid mechanisms of ulcer formation--i.e., impairment of at least one of the defending or protective forces--are also described, as are treatment approaches to ulcer disease. Although suppression of acid secretion is a mainstay of treatment, agents that safely and effectively strengthen the defense are being used more frequently. There are signs that the safe limits for acid-suppressing therapy have been reached or passed. On the other hand, the search for therapy that strengthens the defensive factors has only begun. PMID- 1885903 TI - Pathogenesis and management of gastroesophageal reflux disease. AB - Several pathophysiologic abnormalities known to be associated with the development of gastroesophageal reflux disease (GERD) are reviewed. Among them are the contributions of lower esophageal sphincter pressure, length, and relaxation, the role of hiatal hernia, delayed esophageal acid clearance, and impaired esophageal mucosal resistance. Gastric factors--volume, secretion, the character of the refluxant, and the rate of gastric emptying--also play a role in the pathogenesis of GERD. Treatment requires an individualized approach based on the extent of the symptoms, esophagitis, and other reflux complications. Three phases of treatment--lifestyle modifications, pharmacologic manipulation, and surgery--are discussed, as is maintenance therapy and prevention of recurrent disease. PMID- 1885904 TI - Special diagnostic and therapeutic considerations in elderly patients with upper gastrointestinal disease. AB - Special diagnostic and therapeutic considerations apply to older patients with upper gastrointestinal disease. Age-related anatomical and physiologic changes occur in the major organ systems, affecting functions as diverse as swallowing and hepatic and renal clearance of therapeutic drugs. Because of these factors, and because older patients are more likely to be receiving multiple drugs for concomitant illness, they are more prone to drug-drug interactions and to medication-induced injury of the esophagus and stomach. In addition, several gastrointestinal disorders, notably gastroesophageal reflux and peptic ulcer disease, are commonly seen in the elderly. This report reviews those age-related system changes that affect the gastrointestinal tract, and also reviews the esophageal and gastric disorders that are common and/or particularly problematic in the elderly. Diagnostic techniques to evaluate gastrointestinal disease in older patients and approaches to therapy for this population are described as well. PMID- 1885906 TI - Salmonella septic arthritis. PMID- 1885905 TI - Infection in hospital: a proposal. PMID- 1885907 TI - Failure of fluconazole treatment in cryptococcal meningitis despite adequate CSF levels. PMID- 1885908 TI - Ferritin as the earliest prognostic marker in a case of visceral leishmaniasis. PMID- 1885909 TI - Kingella kingae meningitis in an infant. PMID- 1885910 TI - Cost implications of alternative treatments for AIDS patients with cryptococcal meningitis. Comparison of fluconazole and amphotericin B-based therapies. AB - The extra demands placed upon health care resources by management of AIDS patients have increased the focus on cost implications of therapeutic alternatives. Cryptococcal meningitis is a common life-threatening infection in AIDS patients, usually treated with amphotericin B, often in combination with flucytosine. Administered intravenously, this therapy is associated with frequent and often severe side effects. Fluconazole is a new alternative which can be given orally once daily and has fewer such side effects. The purpose of this study was to examine the cost implications of these different therapies for both primary and maintenance treatment of cryptococcal meningitis. Comparison of these two therapies in recent clinical trials has indicated that fluconazole is at least as effective as amphotericin B, and therefore cost-minimisation analysis is an appropriate method to study the economic consequences of the alternative treatments. Patient management and resource-use information for both treatments was obtained using a modified Delphi technique with a panel of European physicians experienced in the treatment of this disease, and three models were developed to reflect the variability of practice evident among the panel members. U.K. health care costs were used to value these resources. The results indicated that, despite the higher cost of the drug itself, the costs associated with fluconazole were likely to be markedly less than those for amphotericin B for primary treatment, and similar or slightly cheaper for maintenance treatment. Over 1 year of treatment, the saving from the use of fluconazole would be in the range of 4000-14,000 pounds. PMID- 1885911 TI - Concomitant carriage of hepatitis B virus and human T-lymphotropic virus type I among blood donors in Kitakyushu, Japan. AB - The seroprevalence of hepatitis B surface antigen (HBsAg) by gender and age and of human T-lymphotropic virus type I (HTLV-I), and their concomitant carriage was examined among blood donors at the Kitakyushu Red Cross Blood Centre in the fiscal year of 1988. The positive rates of HBsAg among males were consistently higher than those of females; the peaks were detected in male donors aged 30-39 years and in females aged 40-49 years. Declining seropositive rates in individuals aged 50 years or over were observed for both genders. Self-selection due to chronic HBV infection may partly account for such tendencies. On the other hand, the prevalence rates of anti-HTLV-I antibodies among males were uniformly lower than those of females, which must be attributable to male-to-female transmission of HTLV-I via sexual contact. Elevated positive rates in proportion to age were noted for both genders, which may be explained in part by birth cohort effect. The seropositive rates of HBsAg among HTLV-1 carriers were not statistically different from those of non-HTLV-I carriers. Conversely, the prevalence of antibodies to HTLV-I was unrelated to the status of seropositivity of HBsAg. PMID- 1885912 TI - Northwick Park Infection Consultation Service. Part I. The aims and operation of the service and the general distribution of infection identified by the service between September 1987 and July 1990 [see comment]. AB - The Northwick Park Infection Consultation Service (ICS) is a collaborative service operated by the departments of Medical Microbiology and Infectious Diseases where personnel and skills are combined. Its aim is to improve the availability and effectiveness of consultation for infection-related problems. This paper sets out the framework for establishing an ICS and also details the general distribution of infection identified by the Northwick Park ICS in a study carried out between September 1987 and July 1990. Part II assesses the contribution that the ICS made to the management of infection. One thousand and thirty-eight (1038) patients were seen on the ICS. Seventy-five per cent (776) were judged to be infected and in 691 this was a probable or certain diagnosis. Skin and subcutaneous tissue, respiratory tract, and genito-urinary tract infections accounted for 64% of the total. Eighty-seven per cent of infections required treatment with intravenous antibiotics, 22% were associated with concomitant bacteraemia, and 2.7% of patients died as a direct result of their infection. Sixty-four per cent of consultations were unsolicited and arose from laboratory results or the clinical information on the form accompanying the specimen: over one quarter were initiated before results were available. These infections were no different in either severity or nature from those identified by solicited requests to either department. Fifty-three per cent of consultations had a moderate to high clinical component. The results emphasise the importance of infection in hospitals and highlight the advantages of a collaborative approach from the departments of Medical Microbiology and Infectious Diseases. PMID- 1885913 TI - Sputum induction for the diagnosis of pulmonary disease in HIV positive patients. AB - We prospectively compared sputum induction with bronchoalveolar lavage (BAL) in HIV positive patients presenting with acute respiratory episodes and also assessed the effects of using an experienced respiratory physiotherapist on the diagnostic yield from induced sputum. One hundred and fifty-one consecutive patients underwent sputum induction, in 96 the procedure was supervised by nursing and medical staff with no specific expertise (group I); in 55 patients a physiotherapist supervised sputum induction (group 2). Nine patients refused BAL having undergone sputum induction. Of the remaining 142 patients sputum induction failed (no sample expectorated) in 28 patients (25 from group 1 and three from group 2), the sample was inadequate (the material expectorated was not from the lower respiratory tract) in 29, and was adequate in 85 patients. Pneumocystis carinii was diagnosed in 82 patients (51 from group 1 and 31 from group 2). The sensitivity of induced sputum for the diagnosis of P. carinii was 13% and of BAL was 77%. In the subgroup of patients with an adequate induced sputum sample, the sensitivity of induced sputum was 28% and of BAL was 73%. Of the remaining 60 patients, 27 had other diagnoses made by induced sputum and BAL (eight patients), BAL only (15 patients) and induced sputum only (four patients). Eleven patients had bronchitis and responded to oral antibiotics. In 22 patients induced sputum and BAL were negative; alternative diagnoses were established by lung biopsy or by culture of blood, urine or CSF. During sputum induction, 15 patients had nausea and vomiting, eight became dyspnoeic, three had intractable cough and one developed acute bronchoconstriction; 17 patients found the procedure unpleasant. Compared with BAL, induced sputum has a lower diagnostic yield for P. carinii and other pathogens. Use of experienced, dedicated personnel increases the number of successful attempts at sputum induction but does not increase the diagnostic yield. Fibreoptic bronchoscopy and bronchoalveolar lavage remain necessary for patients with negative results from induced sputum and those whose disease course is at variance with the diagnosis made by sputum induction. PMID- 1885914 TI - Northwick Park Infection Consultation Service. Part II. Contribution of the service to patient management: an analysis of results between September 1987 and July 1990. AB - The establishment of Infectious Disease teams combining microbiological and clinical expertise has recently been recommended by a joint working part of the Royal College of Physicians and the Royal College of Pathologists. The Northwick Park Infection Consultation Service (ICS) has been operating on these lines since 1983; details are given in Part I. Part II assesses the contribution that the ICS has made to the management of infection in a study of 1038 patients undertaken between September 1987 and July 1990. The areas of patient diagnosis, treatment, investigation and isolation were examined to assess the appropriateness of the attending doctor's management of infection and the benefits resulting from recommendations made by the ICS. At the time of consultation the correct diagnosis had already been made or considered in 93% of patients, essential investigations needed to confirm or refute the diagnosis performed in 92%, and side-room isolation correctly instituted in 81% of patients requiring it. However, 41% of 776 infected patients were receiving suboptimal treatment: this was significantly more frequent in unsolicited consultations (P less than 0.05). Advice was given following consultation in 893 of 1038 patients (86%) and related to treatment (66%), investigation (41%), diagnosis (30%) and patient isolation (4%). Of 844 patients where receipt of advice could be accurately assessed, it was taken fully in 708 (84%), partly in III (13%), and went unheeded in 25 (3%). Advice on diagnosis or investigation enabled the correct diagnosis to be reached in 30% of consultations and in a further 47 patients (5%), the diagnosis was proposed by the ICS on initial consultation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1885915 TI - Pasteurella haemolytica endocarditis. AB - Although human infections with bacteraemia due to Pasteurella multocida are not uncommon, endocarditis associated with P. haemolytica is rare. We describe such a case in which the patient died despite treatment with apparently appropriate antimicrobial agents. PMID- 1885916 TI - Yersinia enterocolitica biotype 2 serotype O9 septicaemia in a previously fit man, raw goats' milk having been the apparent vehicle of infection: a cautionary tale. AB - A previously fit 66-year-old man presented with a 2 weeks' history of malaise, fever and vomiting which led to a septicaemic illness. Yersinia enterocolitica biotype 2 serotype O9 was isolated from the patient's blood and from raw goats' milk remaining in a bottle after the patient had consumed some of the contents. He also produced antibodies to this serotype. Careful history taking, however, revealed that the bottle of milk had been purchased after the patient became ill. Milk from the same bottle was consumed by his wife who neither became ill nor seroconverted. Furthermore, the organism was not isolated from further samples from the same supplier. The milk consumed by the patient was probably contaminated by him so that initial enthusiasm in attributing his infection to the consumption of raw goats' milk is not supported by the facts. This case illustrates some of the pitfalls of trying to determine the vehicle of infection in a single case. PMID- 1885917 TI - Corynebacterium minutissimum infection. AB - Two cases of infection due to Corynebacterium minutissimum are described. On the basis of biochemical tests the organisms were thought at first to be Corynebacterium jeikeium. Methods of distinguishing between these species and the role of C. minutissimum in the pathogenesis of erythrasma and other skin infections are discussed. PMID- 1885918 TI - Disseminated Candida tropicalis infection following endoscopic retrograde cholangiopancreatography. AB - A necropsy case of a 59-year-old man who developed disseminated Candida tropicalis infection following endoscopic retrograde cholangiopancreatography (ERCP) is reported. Septic fungal infection complicating ERCP has not been described previously. PMID- 1885919 TI - Clinical rubella reinfection--a case of arthropathy. AB - We describe a case of arthropathy due to rubella reinfection. Clinical rubella reinfection with rash and lymphadenopathy has been reported but as far as we are aware this is the first report of a case with arthropathy as the sole presentation. Rubella IgG subclass and avidity tests confirmed the reinfection. PMID- 1885920 TI - Severe hyponatraemia in malaria. AB - We report a case of severe hyponatraemia and hypoglycaemia in a patient with complicated falciparum malaria. The use of large volumes of intravenous dextrose as a diluent for quinine may lead to fluid overload and exacerbate hyponatraemia. PMID- 1885921 TI - Fatal Plesiomonas shigelloides septicaemia in a splenectomised patient. AB - A case of fatal Plesiomonas shigelloides septicaemia is reported in a splenectomised patient. One week prior to his illness the patient was exposed to river water that was potentially contaminated with plesiomonads. Autopsy findings indicated that the plesiomonad may have invaded the blood stream through the terminal ileum. PMID- 1885922 TI - Four years of cryptosporidiosis at GaRankuwa Hospital. AB - Cryptosporidiosis was first recognised at GaRankuwa Hospital, a reference teaching hospital for mainly black patients near Pretoria, South Africa, in October 1985. Since then 289/6870 specimens (4.21%) submitted to the routine stool laboratory have been found to contain Cryptosporidium parvum oocysts. Seasonal peaks were seen in late summer (January, February, March) and minimum case numbers were recorded during late winter (August, September). The disease was predominantly one of early childhood, with the majority of patients being under 3 years of age. Only six positive stools came from patients older than 12 years. Cryptosporidiosis has replaced giardiasis as the most commonly detected gastrointestinal parasitic infection of patients in this hospital. Oocysts were also found in the sputum of an 84-year-old male patient with a persistent productive cough. PMID- 1885923 TI - Two new isolates of Bacillus thuringiensis pathogenic to Spodoptera litura. AB - Both the standard Bacillus thuringiensis kurstaki (HD-1) and the formulated commercial product resulted from this strain have shown limited pathogenicity against the tobacco cutworm (Spodoptera litura). However, two new isolates of Bacillus thuringiensis (K-2074 and K-2178) isolated from Taiwan have been identified through an active screening program to be highly pathogenic against the tobacco cutworm. In this paper, we present results of characterization and the pathogenicity of these two new isolates. PMID- 1885924 TI - Extracellular giant rickettsiae associated with bacteria in the gill of Crassostrea gigas (Mollusca, Bivalvia). AB - Extracellular giant rickettsiae closely associated with bacteria with a Gram negative type wall are reported among the basal insertions of the cilia of the gill epithelium of the oyster Crassostrea gigas (Mollusca, Bivalvia) from the north of Spain. These rickettsiae are extremely pleomorphic cells with a maximum 9 microns length. The internal elements are ribosome-like particles and DNA strands are distributed in some light areas. Some rickettsial cells show one to two vacuole-like dense inclusions formed by curved concentric bands approximately 4 nm thick separated by an approximately 5-nm light space (myelin-like bodies). Numerous bacteria are closely associated with the rickettsiae in the surrounding zone. The cytopathic effects of this association seemed to give rise to the epithelial lysis and concomitant disappearance of the apical microvilli and cilia and the consequent destruction and disintegration of the gill epithelial cells, where these rickettsiae live in close proximity. This is believed to be the first description of extracellular giant pathogenic rickettsiae of these oyster species. PMID- 1885925 TI - Metacestode-induced depression of the production of, and response to, sex pheromone in the intermediate host Tenebrio molitor. AB - Hymenolepis diminuta infection of Tenebrio molitor is associated with an impairment of vitellogenesis and a reduction in host fecundity. In this communication the effect of infection upon an additional aspect of host reproduction, the initiation of mating behavior, has been examined. Copulatory release pheromone, extracted from control virgin females 6-7 days old, was shown to stimulate a positive mating response in 88% of 5- to 6-day-old control males; however, only a 56% response was elicited by pheromone from infected females. In addition, parasitization adversely effected male response to pheromone from control females. A significant (P less than 0.001) depression of copulatory response occurred in infected 6- to 7-day-old males (age of peak response) although this effect was not sustained in older beetles. The possibility that an endocrine interaction between metacestodes and host may mediate these effects is discussed in the light of our knowledge of the role of host juvenile hormone in controlling both pheromone production and vitellogenesis in T. molitor. PMID- 1885926 TI - Surgical templates for the placement of osseointegrated implants. AB - This surgical template can be described as a device that aids in the placement of fixtures during implant surgery. The template helps to achieve not only an accurate position but also the correct angulation. Methods of construction for both the same-arch template and opposing-arch template are described. PMID- 1885927 TI - A multidisciplinary approach in achieving aesthetics and function. AB - This case report illustrates the successful management of a case of mutilated maxillary incisors in a 13 year old patient through a sequence of therapy designed to closely coordinate the various disciplines, endodontics, restorative dentistry and orthodontics, involved. Endodontics was directed towards the control of the infected pulp, restorative treatment was to reconstruct the broken down teeth in stages which were essential in the sequence of treatment, and orthodontics was involved in the achievement of functional occlusion and alignment. The comprehensive treatment approach combined to achieve satisfactory aesthetics and function. PMID- 1885928 TI - Understanding prevention of dental caries and gum disease in an Asian community. AB - Prevention is recognized as a cost-effective method for the control of oral diseases. Knowledge of prevention can influence preventive dental behaviour. This study surveyed knowledge on the prevention of dental caries and gum diseases among a selected group of adults. Respondants were asked to indicate the importance of numerous preventive measures for prevention of both categories of oral diseases. Results showed that while respondents appropriately identified the importance of regular brushing for prevention, the role of flossing is underestimated. Similarly, there was a lack of appreciation for the value of various fluoride treatment modalities in preventing dental caries. A lack of understanding of dental sealants was also evident. It is concluded that public knowledge on prevention of dental caries and gum disease deviates greatly from current scientific information. PMID- 1885929 TI - [Looking back upon my 29 years' career--challenge to Angle's orthodontics]. PMID- 1885930 TI - [Interrelation of tooth crown diameters]. AB - The purpose of this study was to clarify the interrelation of the tooth crown diameters using statistical methods. The material consisted of 414 dental casts from orthodontic patients in the Japanese female. The mesiodistal diameters of all permanent teeth on the left side were measured, excluding the third molars. These values were examined by correlation coefficient matrix and multivariate analyses such as multiple regression, principal component and canonical correlation, etc. The results were as follows: 1) The tooth crown diameters showed a strong intercorrelation within each jaw and between both jaws. 2) When the incisors and the canine were large in size, the premolars and the molars tended to be small. 3) When the incisors and the molars were large in size, the canine and the premolars tended to be small. 4) When the incisors and the premolars were large in size, the canine and the molars tended to be small. 5) All of the teeth except the upper lateral incisor were classified according to size into the four groups of incisors, canines, premolars and molars. 6) The dentition with small teeth tended to show a spaced arch. PMID- 1885931 TI - [Autogenous dermal grafts for repair of temporomandibular joint disc perforations]. AB - Perforations of the temporomandibular joints (TMJs) disc were made in the rabbits and repaired with autogenous dermal grafts. The healing process was investigated histologically. Twenty-one rabbits (forty-two TMJs) were divided into 3 experimental groups. Group 1. Six TMJs in which the superior aspects of the discs were exposed by the incision of the articular eminence. Group 2. Fifteen TMJs in which the discs were perforated. Group 3. Twenty-one TMJs in which the dermal grafts were sutured on the disc perforations. The results obtained were as follows: In group 2, all perforations were not repaired, except in one case. In group 3, 14/19 grafted disc perforations were repaired. One week after surgery, young, loose, collagenous tissue from the synovial membrane lined the margins of the perforations. Two weeks after surgery, vascularity from the synovial membrane and young collagen fibers were seen in the area of the repaired perforations. Four weeks after surgery, long and thick collagen fibers bridged the perforations. PMID- 1885932 TI - [Tissue response after preparation of implant cavity]. AB - The purpose of this study is to discuss the structural changes of the surrounding tissue around the implant cavity when the influence of tooth extraction is still remaining. At 3 months after the extraction of the dog lower teeth, implant cavities were prepared. Histological examinations were performed on the specimens at 30 minutes, 2 days, 5 days and 10 days. RESULTS: 1) At 3 months after the tooth extraction, enhanced bone remodeling looks like a typical one in the compact bone area. 2) The bones formed after the extraction, by alternate resorption and formation with time, were replaced by higher differentiated ones. 3) At 5 days, by the implant cavity formation, bone addition is seen on the inner and outer surfaces of the compact bone. 4) Inside the extraction socket, the changes in the shape and structure of the trabeculae, which are influenced by the implant cavity preparation, are seen near the deep zone of the implant cavity and gradually with time they could be seen in the shallow zone and away from the implant cavity. 5) The newly formed trabeculae inside the implant cavity are mainly type I and on a part of the surface there is the addition of type II. PMID- 1885933 TI - [Studies on the structure of the matrix in cementum regenerated in healing process of periodontal tissues]. AB - The purpose of this study was to investigate the structure of the matrix in regenerated cementum on surgically denuded root dentin and on acid-demineralized root dentin in dogs. Non-decalcified specimens were examined two to 16 weeks after surgery. The arrangement of the matrix fiber, the fiber component and the crystal deposition of the cementum were studied by light microscopy and electron microscopy. The results were as follows: 1. There were many differences in the structures of regenerated cementum. The differences were dependent on the presence of resorption of the root dentin, existence of lamellar structure, and density of Sharpey's fibers. 2. Regions without surface resorption of dentin exhibited a dense deposition of crystallites and a rare arrangement of collagen fibrils at the cementodentinal junction. 3. Regions of surface resorption of dentin exhibited a layer where dentinal and cemental crystallites were amalgamated, and/or dentinal and cemental matrix fibers were interdigitated at the cementodentinal junction. 4. Regions subjected to artificial demineralization by citric acid exhibited similar structure to that where surface resorption of dentin was observed. 5. It is suggested that the resorption of dentinal surface during the healing process of a surgically created wound in periodontal tissue occurred as an intermediate stage followed by the establishment of a stronger bind by the increase of superficial contact area at the cementodentinal junction. PMID- 1885935 TI - [Response properties of pulpal nerve fibers with different conduction velocities]. AB - Tapering and branching of the nerve fibers cause the conduction velocity (CV) along the axon to be unequal. The purpose of this study was to investigate the response properties of the myelinated and unmyelinated nerve fibers in the cat tooth pulp. Electrophysiological recordings were made from the functional single fibers innervating the lower canine tooth pulp in 25 adult cats anesthetized with pentobarbital sodium after the application of four types of stimuli to the canine tooth. A total of 272 single pulpal nerve fibers was identified. A-fibers (n = 215) were divided into two groups: One (Ac, n = 55) consisting of the fibers whose intrapulpal CVs were less than 2 m/s and the extra-pulpal CVs of more than 2 m/s, and the other (At, n = 160) consisting of the fibers whose CVs were more than 2m/s both inside and outside the tooth pulp. Fifty-seven C-fibers (C) were also found. None of C, 47% of At and 46% of Ac responded to the rapid elevation of the temperature. None of At, 38% of Ac and 53% of C responded to the continuous heat. None of C, 20% of At and 20% of Ac responded to the hydrostatic pressure. None of At, 86% of Ac and all of C responded to bradykinin. These results suggest that the functional difference between the pulpal A-and C-fibers is not clear and that the Ac-fibers may complicate the dental and pulpal pain. PMID- 1885934 TI - [Statistical study of endodontically treated teeth by undergraduate students from 1979 to 1989]. AB - In clinical education in dentistry, it is very important and significant that the undergraduate students themselves treat the patients. According to the rapid progress of dental science, the complexity and the high degree of the quality of education increase more and more, so that it is a requisite to make our efforts to enrich the quality of the practice at all times. In this paper, we investigated and statistically analyzed the result of 3,359 cases (test cases: 304, general cases: 3,055) which were treated endodontically by the undergraduate students of Tokyo Medical and Dental University in the four classes of 1979, 1982, 1986 and 1989. Both the number of the treated cases and the patients decreased year by year. Only the patients above sixty years old showed a tendency to increase in number. The result of the test cases was not always representative of the result of the general cases. If the clinical instructors for the undergraduate students grasp the detailed results of this study, we can expect that they can guide and train the undergraduate students more effectively. PMID- 1885936 TI - [Dental anthropological study of Mongoloid in China]. AB - The purpose of this study was to evaluate the craniofacial and occlusal characteristics of the inhabitants in China. The material consisted of cephalograms, pantomograms, dental casts and anthropological measurements taken from 517 inhabitants: 416 Han Chinese in Beijing, Shanghai, Guangzhou and Changchun and 101 Mongolians in Hohhot. The data were compared among the above five regions and also with the Japanese data. The findings were summarized as follows: I. Craniofacial characteristics; a) The Han Chinese and the Mongolians showed brachycephaly. b) The inhabitants in Guangzhou showed a tendency of bimaxillary protrusion with a smaller facial height, and the inhabitants in Changchun showed a larger gonial angle with a larger facial height than those of the other regions. c) The Mongolians had a larger value of the saddle angle and of the bi-gonial breadth. d) Compared with the Japanese, their craniofacial complex was characterized by a larger facial angle, smaller mandibular plane angle and a smaller gonial angle. II. Occlusal characteristics; a) The inhabitants in China had a similar tendency in the dental arch form and in the dental trait frequency. b) The inhabitants in Beijing had a larger mesiodistal crown-diameter of the anterior teeth than those in the other regions. c) Compared with the Japanese, their teeth were characterized by a smaller mesiodistal crown diameter (especially on the upper first molar), higher frequency of shovel-shape and lower frequency of Carabelli's tuberculum. PMID- 1885937 TI - Physician authority for unilateral DNR orders. PMID- 1885938 TI - The Alcoholic Beverages Labeling Act of 1988. A preemptive shield against fetal alcohol syndrome claims? PMID- 1885939 TI - The physician's license: an Achilles' heel? PMID- 1885940 TI - Negligence liability for transfusion-associated AIDS transmission. An update and proposal. PMID- 1885941 TI - Regulation of mail-order pharmacy. A critique. PMID- 1885942 TI - Pre-S1 and Pre-S2 gene-encoded proteins in liver and serum in chronic hepatitis delta infection. AB - Frozen cryostat sections and sera from 30 patients with chronic delta infection were examined for pre-S1 and pre-S2 gene-encoded proteins, and the results were compared to markers in liver and serum HBV and HDV replication. Pre-S1 and pre-S2 were detected by indirect immunofluorescence (IF) in the liver in all 26 patients with histochemically demonstrable HBsAg. Pre-S peptides were found by double IF to have a predominantly cytoplasmic expression and to be located in the same hepatocytes expressing HBsAg. Liver cells expressing hepatitis delta antigen (HDAg) were frequently negative or very weakly positive for HBsAg and pre-S peptides, but occasional HDAg positive hepatocytes were also strongly positive for HBsAg and for pre-S peptides, particularly pre-S2. Circulating pre-S1 was detected in 24 patients (80%) and pre-S2 in 27 (90%). Detection of pre-S peptides in liver and serum was independent of HBV and HDV replication and of the HBV-DNA integration state. There was no correlation between the amount of circulating pre S peptides and serum HBV-DNA and HDV-RNA. These results indicate that in chronic HDV infection, formation and secretion of pre-S peptides and of HBsAg occur independently of HBV and HDV replication and secretion. They further indicate that in the acquisition by replicating HDV of an HBV-derived envelope in the liver, both HBsAg and pre-S peptides are concomitantly available but circulating HDV-RNA is not invariably associated with the presence of these peptides in serum. PMID- 1885943 TI - Demonstration of concurrent dengue 1 and dengue 3 infection in six patients by the polymerase chain reaction. AB - A dual viremia resulting from naturally acquired dengue 1 and dengue 3 infections in six patients experiencing a dengue-like syndrome during the epidemic in New Caledonia in 1989 is reported. Serotype identification was first based on virus isolation in mosquito cells and immunofluorescence using type-specific monoclonal antibodies. The double infection was confirmed directly in blood samples by the polymerase chain reaction (PCR) on genomic RNA and hybridization of the amplified cDNA fragments with type-specific DNA probes. PMID- 1885944 TI - Lack of immunity to hepatitis B virus among the expatriates residing in southern Taiwan. AB - Taiwan is an endemic area for hepatitis B virus (HBV) infection. There are more than 3-million carriers on this island. Chronic HBV infections may result in liver cirrhosis and hepatocellular carcinoma, which are common in Taiwan. However little information is available concerning the immunity and the susceptibility to HBV among the expatriate-population (non-permanent residents from foreign countries) in Taiwan. Thus controversies exist on the indications for HBV vaccination among the foreign visitors and expatriates. This study evaluated the serological status of those who attended the Kaohsiung Adventist Clinic between May 1986 and August 1989. Hepatitis B surface antigen (HBsAg) and antibody (anti HBs) were determined by ELISA. A total of 152 expatriates (85M, 67F, aged 5 to 64 years, duration of residence in Taiwan: 2 weeks to 11 years) without previous HBV vaccination, were tested. HBsAg and anti-HBs were not detected in 125 (82%). Anti HBs was found in 22 (15%). There was no correlation between the duration of residence and anti-HBs positivity. However, there was an increased prevalence of anti-HBs with increasing age after 30. For those expatriates who were anti-HBs positive, 64% had a history of sexual contact with a partner from an endemic area of HBV. HBsAg was detected in 5 (3%). Three were symptomatic with abnormal liver function tests. Four had a history of sexual exposure. Their children were not antigenemic. It is concluded that most (greater than 82%) of the expatriates residing in southern Taiwan have no immunity to HBV and sexual contact is a major route (70%) of transmission.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1885945 TI - Effect of rimantadine on the immune response to influenza A infections. AB - The effects of rimantadine on lymphocyte responses to mitogens CON-A and PHA, natural killer cell activity, and the development of serum and local antibodies were studied during an epidemic outbreak of influenza A (H3N2). Twenty-three families consisting of 38 adults and 46 children had a member who developed a flu like illness and were randomly assigned to receive placebo or rimantadine either as treatment or post exposure prophylaxis. Nasal washings for virus isolation and IgG and IgA determination were collected on days 1, 5, and 10 of illness. Blood samples for immunologic studies were obtained on days 1 and 5 of clinical illness and on day 21. No differences in lymphocyte responses to CON-A and PHA or in natural-killer cell activity were noted between placebo and rimantadine groups. The development of neutralizing antibodies to influenza H3N2 was also not affected by rimantadine. However, the presence of IgA in nasal secretions was significantly diminished in the rimantadine group compared to the placebo group (0/9 vs. 6/9, P less than 0.005). The findings indicate that rimantadine had no adverse affect on the systemic immune system. However, local immune response was diminished in individuals taking rimantadine possibly due to the presence of less immunogen resulting from reduction of virus in secretions of individuals taking antivirals. PMID- 1885947 TI - Male infertility following spinal cord injury. AB - Ejaculatory dysfunction and poor semen quality are responsible for male infertility following spinal cord injury (SCI). Techniques which have been used to obtain semen include intrathecal neostigmine, subcutaneous physostigmine, direct aspiration of sperm from the vas deferens, vibratory stimulation and electroejaculation. Vibratory stimulation and electroejaculation are most widely used in the United States and have a 50-90% success rate at obtaining semen. Poor semen quality following SCI has been attributed to stasis of semen, testicular hyperthermia, urinary tract infections, sperm contact with urine, possible changes in the hypothalamic-pituitary axis, chronic use of various medications and possible sperm antibodies. The outlook for having a child following SCI continues to improve with advancements in obtaining and processing sperm and assisted reproductive technologies. PMID- 1885946 TI - Reinfection of mice with respiratory syncytial virus. AB - A BALB/c model of respiratory syncytial virus infection has been developed in which high-titered replication occurs in lung, immunological infiltrates in lung can be detected histologically, and illness can be consistently reproduced. The immunodeterminants of RSV reinfection in this system were investigated by rechallenging mice with RSV early (less than 2 months after primary infection) and late (16 to 21 months after primary infection) and correlating illness and titer of RSV isolated from lungs and noses with RSV-specific serological responses and lung histology. After early rechallenge, RSV was cleared within 24 hours from both nose and lung. After late rechallenge, RSV was isolated at 72 hours from nose in 21/24 mice, but from lung in only 5/24 mice. Isolation of RSV from lung after rechallenge was associated with low RSV-specific antibody titers measured by ELISA and plaque-reduction neutralization. The presence of lymphocyte aggregates around the bronchovascular bundles was associated with inability to isolate RSV from lung and lack of illness. The basophilic lymphocytes were small and uniform in size with dense nuclei and a small amount of cytoplasm. These studies demonstrate that nasal and pulmonary reinfection with RSV is possible in mice after late rechallenge. The studies also indicate the potential importance of RSV-specific antibody in protecting lung from reinfection. PMID- 1885948 TI - The impact of spinal cord injury on female sexuality, menstruation and pregnancy: a review of the literature. AB - Spinal cord injury (SCI) results in alterations in sexual functioning. This area has been studied in depth in males; however, the literature pertaining to female sexual dysfunction after injury is sparse and focused primarily on menstruation and pregnancy. This report reviews the literature on female sexuality, menstruation and pregnancy after SCI and discusses the findings. PMID- 1885949 TI - Psychological assessment and treatment of sexual dysfunctions following spinal cord injury. AB - Sexual dysfunction following SCI has received increased attention in recent years. Despite this attention, many physicians and allied health care workers respond to patients' sexual concerns with dismissal or reassurance. Moreover, physiological and medical aspects of sexual dysfunction tend to be emphasized at the exclusion of the emotional aspects of sexuality. A multidimensional, integrative approach to the assessment and treatment of sexual dysfunctions across the entire sexual response cycle following SCI is emphasized. The rationale and procedure of brief sexual counseling is discussed. PMID- 1885950 TI - Spontaneous pneumomediastinum presenting with dysphonia in a patient with anterior spinal artery syndrome: a case report. AB - The presence of spontaneous pneumomediastinum in otherwise healthy adults is an uncommon clinical entity. An unusual case presented in a patient with anterior spinal artery syndrome with paraplegia where progressive dysphonia was the primary presenting symptom. The clinical features, treatment and proposed pathophysiology for this condition are presented. PMID- 1885951 TI - The proximal tap or "central Tinel" sign in central dysesthetic syndrome after spinal cord injury. AB - Diffuse, chronic, and dysesthetic pain following spinal cord injury (SCI) has been described by several authors under different terms. As illustrated by the two patients described here, central dysesthetic syndrome (CDS) can be mistaken for musculoskeletal, peripheral neuropathic or visceral disease in SCI patients. In these patients, an added clue to the central neuropathic nature of their symptoms was allesthesia and allodynia to light touch or tapping over areas rostral to the level of injury; this may be called the proximal tap or "central Tinel" sign. PMID- 1885952 TI - Cultural considerations in child-rearing practices: a transcultural perspective. AB - The nursing profession has begun to see the necessity of considering an individual's cultural belief system when providing nursing care. Leininger (1978), the founder of transcultural nursing, takes a strong position that "...a nurse should not be viewed as professional until she can effectively work with people in at least a bicultural setting, and the professional nurse should be prepared to respond effectively to people in our pluralistic world as an essential criterion of being professional" (pg. 141). To intervene effectively with the parent-child subsystem, the nurse must take into consideration the parental figure's belief system and cultural values. These cultural values give parents a sense of direction as well as meaning to their life. If nurses fail to respect and incorporate these values into nursing care, their ability to effectively help these parent-child subsystems is impaired and can limit this subsystem's progress toward their own culturally defined health state (Leininger, 1978). The purpose of the article is to provide nurses with a framework that can be used when interacting with families from diverse cultural backgrounds concerning the issue of discipline. This article emphasizes the need to incorporate a culturological assessment when implementing nursing interventions. PMID- 1885953 TI - Testicular self-examination among African-American men. AB - The protection of African-American men from testicular cancer is a misnomer. Of the new cases of testicular cancer diagnosed in the United States, one-fourth will be among African-Americans. Nine out of every ten testicular tumors are discovered by the man himself. Therefore, the American Cancer Society recommends that all men practice testicular self-examination every month and make the procedure a life-time habit. Research suggests that most men are unaware of the fact that cancer can develop in the testicles. And, among African-American men this lack of knowledge is even greater. PMID- 1885954 TI - A comparison of black and white family caregivers experience with dementia. AB - The chronicity of dementia and the ever-increasing need for care of those afflicted, places tremendous burden on the family and those individuals who assume primary responsibility for caregiving. In this descriptive study, the investigators report findings comparing Black and White families' experiences with dementia, specifically, the problems associated with caregiving, the coping strategies used by the caregivers and the various forms of supportive modalities that help family caregivers provide care. Study findings indicated differences between the Black and White caregivers in identifying the single most difficult problem that they had in caring for their confused relative. Differences in coping strategies between the two groups of caregivers are noted as well. Black caregivers of all ages used religious faith as a primary means of coping with the stresses of caregiving while White caregivers tended to seek help from professionals and use problem-solving methods. The implications of the study findings for structuring interventions are discussed. Implications of this study concern three areas: 1) respite services; 2) individual and family counseling; and 3) education. PMID- 1885955 TI - Health care crisis in the black community: challenges prospects, and the black nurse. AB - The Black community, particularly in major urban settings, is faced with escalating social, economic, and life-style problems, which threaten the life and well-being of current and future generations of Black people in crisis proportion. The rising number of deaths due to heart disease and stroke, homicide and accidents related to substance abuse, AIDS, cancer, and infant mortality are among the leading culprits. They interfere with prospects of longevity, joblessness, poverty, and homelessness and further complicate the crisis. These problems have implications for the practice of nursing. The magnitude of the problems dictate the need for modifications in the health care delivery system and how future practitioners of nursing are educated. The inextricable role of the community, although often underaddressed, in solving its own problems is among the promising strategies for resolving the crisis. Black nurses, in particular, must accept the challenge and the opportunity to test innovative and sensitive interventive strategies which will enable the Black community to emerge from the complex and haunting problems which threaten well-being. PMID- 1885957 TI - A retrospective analysis of the registered care technologist (RCT) proposal. AB - This article reviews, in retrospect, the Registered Care Technologist proposal previously advanced by the American Medical Association. It argues that an analysis of this proposal is a useful way of understanding interest group theory. Further, it makes a case for nurses in general and Black nurses in particular to understand this theory from an economic perspective. Finally, it urges all nurses to continue to collectively utilize power. PMID- 1885956 TI - Cancer control by the year 2000: implications for action. AB - This article presents an overview of the overall cancer incidence and mortality rates within the United States. More specifically, it addresses the high cancer incidence and mortality rate within the Black community. Included are the guidelines for the National Cancer Institute for cancer control to be achieved by the year 2000. In order to achieve these goals, Black nurses must actively participate in developing, implementing, and evaluating primary and secondary cancer prevention initiatives that will assist in reducing the disproportionate impact of cancer upon Black Americans. PMID- 1885958 TI - Nursing education and practice for the 21st century: forecasting an agenda for historically/predominantly black colleges and universities. AB - The social worth and contribution of the historically Black colleges and universities has been well documented. We have only to look at Blacks who are in leadership positions to understand that the majority of these leaders have received their basic undergraduate preparation in historically Black colleges and universities. Dr. Elizabeth Carnegie who has recorded the Black nurses who have been admitted to the American Academy of Nursing states that most of the Black fellows are graduates of historically Black colleges and universities. The five minority fellowship programs in nursing, psychology, psychiatry, social work and sociology funded by NIMH have identified 97.3% of the Black fellows are graduates of historically Black colleges and universities. PMID- 1885959 TI - Quality control as a system for maintaining desired standards in production. PMID- 1885960 TI - A comparative study of the bedtime routines and sleep of older adults. PMID- 1885961 TI - Community health nursing and the AIDS pandemic: case report of one community's response. AB - The World Health Organization (WHO) currently projects that there may be a cumulative total of 30 million cases of Acquired Immune Deficiency Syndrome (AIDS) worldwide by the year 2000 ("WHO Predicts," 1991). Community health nurses (CHNs), particularly those employed by local and state health departments, have a major role to play in the worldwide public health effort being mounted in response to the AIDS pandemic. CHN roles may include: direct caregiver, advocate, case manager, health educator, program planner, program coordinator, and policy advocate. How CHNs contribute to the effort against AIDS in various CHN roles is illustrated through a case report of a Midwestern U.S. suburban community's response to AIDS. The community's response was fostered and an AIDS program developed and implemented by CHNs employed by the community's health department. In addition to enabling this community to respond to AIDS in a humane and caring manner, the CHN initiatives have resulted in positive community feelings about the health department, and enhanced the image of CHNs as innovators and facilitators of change. PMID- 1885962 TI - Self-perceived needs of primary caregivers of home-hospice clients. AB - The purpose of this study was to assess the self-perceived needs of primary caregivers of terminally ill home-hospice clients. A home interview was conducted using an instrument based on the Neuman Systems Model. Data were analyzed in relation to intrapersonal stressors (within the individual), interpersonal stressors (between the individual and others), and extrapersonal stressors (between the individual and the environment). Five community nursing diagnoses (Porter, 1987) were identified: (a) Population at risk for health problems, (b) population at risk for role constriction/role fatigue, (c) population at risk for insufficient support, (d) population at potential risk for lack of information, and (e) population at potential risk for lack of service coordination. Early attention to limiting the impact of stressors on the caregiver can improve the caregiver's ability to care for the hospice client. PMID- 1885963 TI - Support and education for the caregiver and client in the home: an inservice project for community health nurses. AB - This article discusses an inservice project implemented at the Berks County Visiting Nursing Association (VNA) in Reading, PA. The topic of support and education for the nonprofessional caregiver as an area in which staff nurses are lacking information is identified. Background information gleaned from a literary review is presented. Implementation and evaluation of the inservice project is discussed. PMID- 1885964 TI - Differences in technology among subspecialties in community health nursing. AB - Interest in differentiating community health nursing from home health nursing has focused on theoretical models, concepts, and examinations of the historical origins and evolution of the roles. Although not usually included in the recent differentiation efforts, school and occupational health nursing traditionally have been considered important subspecialties of community health nursing. Utilizing an approach to technology developed by organizational researchers and focusing not on hardware and equipment, but on the characteristics of the raw materials and techniques employed, this study examined the differences among public health/community health, home health, school health, and occupational health on the three technological dimensions of uncertainty, instability, and variability. Survey data from nurses in the four areas (N = 40) were utilized. Results indicated that home health nursing differed significantly from the other groups on the dimensions of uncertainty and instability. PMID- 1885965 TI - Documentation of client encounters by public health nurses at a county health department. AB - Documentation of high-risk infant (HRI) encounters in the nursing flowsheet by public health nurses (PHNs) at a county health department is evaluated for its effectiveness. A convenience sample of 31 client records was used. The effectiveness in documentation was evaluated in terms of PHNs' adherence to guidelines provided for the use of the particular nursing flowsheet. The frequency of correct documentation was determined for assessment, intervention, and outcome measures. Within the category of assessment, a high rate of correct documentation was found for the items, elimination, and bonding status. A moderate rate of correct documentation was noted for items pertaining to physical assessment, health-care system used, child abuse and neglect potential in the home, and safety. Documentation of anticipatory guidance or intervention provided was minimal throughout the flowsheet. The outcome measures, expressed as goal statements, were by comparison, more often documented correctly. PMID- 1885966 TI - Community as client: a "hands-on" experience for baccalaureate nursing students. AB - This article describes how Bachelor of Science in Nursing (BSN) students are introduced to the concept of community as client. Although this concept is widely accepted, at least theoretically, the majority of community health nursing practicums for baccalaureate students are in working with individuals and families as clients. The community health nursing faculty at La Roche College believe that undergraduate students should not only have the experience of decision making and problem solving at the individual and family level but also at the aggregate or community level. The process of actualizing the community as client concept through "hands on" experience is the focus of this article. Our student body consists of registered nurses seeking their baccalaureate degree in nursing. PMID- 1885967 TI - Geniculate neuralgia: the surgical management of primary otalgia. AB - Intractable, unexplained deep-ear pain presents a rare, albeit significant problem in otolaryngological and neurosurgical practice. The authors review their experience with 18 cases of primary otalgia during the past 15 years. A total of 31 surgical procedures were performed. Seventeen patients had sequential rhizotomies and one patient had microvascular decompression alone. Based on the clinical diagnosis, the nerves sectioned were singly or in combination: the nervus intermedius (14 patients), geniculate ganglion (10 patients), ninth nerve (14 patients), 10th nerve (11 patients), tympanic nerve (four patients), and chorda tympani nerve (one patient). Microvascular decompression of the involved nerves was undertaken in nine patients, in whom vascular loops were discovered. Adhesions (six patients), thickened arachnoid (three patients), and benign osteoma (one patient) were other intraoperative abnormalities noted. The overall success of these procedures in providing pain relief was 72.2%, and the mean follow-up period was 3.3 years (range 1 month to 14.5 years). There was no surgical mortality. Expected side effects were: decreased lacrimation, salivation, and taste related to nervus intermedius nerve section, and transient hoarseness and diminished gag related to ninth and 10th nerve section. Four patients developed sequelae consisting of sensorineural hearing loss, vertigo, and transient facial nerve paresis. One patient had a cerebrospinal fluid leak and another developed aseptic meningitis as postoperative complications. Except when primary glossopharyngeal neuralgia is the working diagnosis, a combined posterior cranial fossa-middle cranial fossa approach is recommended for adequate exploration and/or section of the fifth, ninth, and 10th cranial nerves as well as the geniculate ganglion and nervus intermedius. PMID- 1885968 TI - Stereotactic radiosurgery for arteriovenous malformations of the brain. AB - Stereotactic radiosurgery successfully obliterates carefully selected arteriovenous malformations (AVM's) of the brain. In an initial 3-year experience using the 201-source cobalt-60 gamma knife at the University of Pittsburgh, 227 patients with AVM's were treated. Symptoms at presentation included prior hemorrhage in 143 patients (63%), headache in 104 (46%), and seizures in 70 (31%). Neurological deficits were present in 102 patients (45%). Prior surgical resection (resulting in subtotal removal) had been performed in 36 patients (16%). In 47 selected patients (21%), embolization procedures were performed in an attempt to reduce the AVM size prior to radiosurgery. The lesions were classified according to the Spetzler grading system: 64 (28%) were Grade VI (inoperable), 22 (10%) were Grade IV, 90 (40%) were Grade III, 43 (19%) were Grade II, and eight (4%) were Grade I. With the aid of computer imaging integrated isodose plans for single-treatment irradiation, total coverage of the AVM nidus was possible in 216 patients (95%). The location and volume of the AVM were the most important factors for the selection of radiation dose. Magnetic resonance (MR) imaging was performed at 6-month intervals in 161 patients. Seventeen patients who had MR evidence of complete obliteration underwent angiography within 3 months of imaging: in 14 (82%) complete obliteration was confirmation being 4 months (mean 17 months) after radiosurgery. The 2-year obliteration rates according to volume were: all eight (100%) AVM's less than 1 cu cm; 22 (85%) of 26 AVM's of 1 to 4 cu cm; and seven (58%) of 12 AVM's greater than 4 cu cm. Magnetic resonance imaging revealed postirradiation changes in 38 (24%) of 161 patients at a mean interval of 10.2 months after radiosurgery; only 10 (26%) of those 38 patients were symptomatic. In the entire series, two patients developed permanent new neurological deficits believed to be treatment related. Two patients died of repeat hemorrhage at 6 and 23 months after treatment during the latency interval prior to obliteration. Stereotactic radiosurgery is an important method to obliterate AVM's, especially those previously considered inoperable. Success and complication risks are related to the AVM location and the volume treated. PMID- 1885969 TI - Aneurysms of the intracavernous carotid artery: a multidisciplinary approach to treatment. AB - Of 43 cavernous sinus aneurysms diagnosed over 6 1/2 years, 23 fulfilled indications for treatment; of these 19 were treated, eight surgically and 11 with interventional radiological techniques. Six small and two giant aneurysms were treated surgically: four were clipped, two were repaired primarily, and two were trapped with placement of a saphenous-vein bypass graft. Seven large and four giant aneurysms were treated with interventional radiological techniques: in five cases the proximal internal carotid artery (ICA) was sacrificed; one aneurysm was trapped with detachable balloons; and five were embolized with preservation of the ICA lumen. The mean follow-up period was 25 months. At follow-up examination, three patients in the surgical group were asymptomatic, two had improved, and three had worsened. Three of these patients had asymptomatic infarctions apparent on computerized tomography (CT) scans. At follow-up examination, four radiologically treated patients were asymptomatic, five had improved, two were unchanged, and none had worsened. One patient had asymptomatic and one minimally symptomatic infarction apparent on CT scans; both lesions were embolic foci after aneurysm embolization with preservation of the ICA. It is concluded that treatment risk depends more on the adequacy of collateral circulation than on the size of the aneurysm. A multidisciplinary treatment protocol for these aneurysms is described, dividing patients into high-, moderate-, and low-risk groups based on pretreatment evaluation of the risk of temporary or permanent ICA occlusion using a clinical balloon test occlusion coupled with an ICA-occluded stable xenon/CT cerebral blood flow study. Radiological techniques are suggested for most low-risk patients, while direct surgical techniques are proposed for most moderate- and high-risk patients. PMID- 1885970 TI - Determination of cerebrospinal fluid shunt obstruction with magnetic resonance phase imaging. AB - The cerebrospinal fluid (CSF) flow rates in 12 patients with symptoms suggestive of CSF shunt obstruction were measured with magnetic resonance (MR) phase imaging. The shunts were imaged over the skull, just distal to any reservoir, using a curved surface coil. Images perpendicular to the direction of flow were made on a 1.5-tesla clinical unit with a flow-sensitive pulse sequence. The patients' ages ranged from 2 months to 28 years. All patients had ancillary investigations to determine the functional status of the shunt. No flow was detected in seven patients with blocked shunts. Flow rates between 3 and 40 cc/hr were found in three patients with functioning shunts. Two patients, one with a blocked shunt and one with a functioning shunt, could not be imaged due to motion artifact. Magnetic resonance phase imaging is a promising technique in the determination of CSF shunt obstruction. PMID- 1885971 TI - Ventricular cerebrospinal fluid eosinophilia in children with ventriculoperitoneal shunts. AB - To determine the significance of cerebrospinal fluid (CSF) eosinophilia, the charts of 106 patients treated with shunt-related procedures during the calendar year 1985 were reviewed. Sixty-nine patients presented for a shunt revision; their charts were retrospectively reviewed from the time of shunt insertion until January, 1988. The remaining 37 patients had a ventriculoperitoneal shunt inserted during the study period and were subsequently followed to January, 1988. A total of 558 shunt-related procedures were performed on these patients during the study period, with a mean follow-up period of 6.9 years. The infection rate was 3.8%. Eosinophilia was diagnosed when eosinophils accounted for 8% or more of the total CSF white blood cell count. Ventricular CSF eosinophilia occurred in 36 patients sometime during their clinical course. These 36 patients required a mean of 8.5 shunt revisions, while the remaining patients required a mean of 2.5 revisions (p less than 0.001). Shunt infections were also more frequent in patients with eosinophilia (p less than 0.01). In no case was peripheral eosinophilia or a parasitic infection present. This study demonstrates that CSF eosinophilia is common in children with shunts. Children with this laboratory finding will experience more shunt failures. In addition, the new appearance of eosinophilia in the CSF of a patient with a shunt in place suggests the possibility of a shunt infection. PMID- 1885972 TI - Hyperglycemia and neurological outcome in patients with head injury. AB - To examine the relationship between serum glucose and the outcome of patients suffering from head injury, the authors retrospectively reviewed the clinical course of 169 patients admitted for treatment to Harborview Medical Center (a regional trauma center). All patients underwent craniotomy for evacuation of intracranial hematoma and/or placement of a subarachnoid bolt for intracranial pressure monitoring under general anesthesia. Patients with a Glasgow Coma Scale (GCS) score of 8 or less had significantly higher serum glucose levels than patients with GCS scores of 12 to 15 (mean +/- standard error of the mean 192 +/- 7 mg/dl vs. 130 +/- 8 mg/dl or 10.7 +/- 0.4 mmol/liter vs. 7.2 +/- 0.4 mmol/liter) (p less than 0.0001). Patients who subsequently remained in a vegetative state or died had significantly higher glucose levels both on admission and postoperatively than patients who had good outcome or moderate disability (217 +/- 12 mg/dl vs. 167 +/- 6 mg/dl or 12.1 +/- 0.7 mmol/liter vs. 9.3 +/- 0.3 mmol/liter on admission, and 240 +/- 16 mg/dl vs. 156 +/- 5 mg/dl or 13.3 +/- 0.9 mmol/liter vs. 8.9 +/- 0.3 mmol/liter postoperatively) (p less than 0.0001). Among the more severely injured patients (GCS score less than or equal to 8), a serum glucose level greater than 200 mg/dl (11.1 mmol/liter) postoperatively is associated with a significantly worse outcome (p less than 0.01). The authors conclude that severely head-injured patients frequently develop hyperglycemia and the elevated serum glucose level may aggravate ischemic insults and worsen the neurological outcome in such patients. PMID- 1885973 TI - Subarachnoid hemorrhage in sickle-cell disease. AB - The neurological complications of sickle-cell disease include cerebral intracerebral hemorrhage; subarachnoid hemorrhage (SAH) has been infrequently reported. Among 325 patients with sickle-cell disease followed at the University of Illinois between 1975 and 1989, 11 cases of SAH were identified. Aneurysms were found in 10 of these patients, three of whom had multiple aneurysms. All of the patients had some degree of anemia and nine underwent craniotomy without hematological or neurological complications. From this review it appears that SAH is not uncommon in sickle-cell disease patients and tends to occur at a younger age and with smaller aneurysm size than in the general population. With proper perioperative management, including exchange transfusions to reduce the proportion of hemoglobin S to less than 30%, these patients can undergo angiography and craniotomy without an increased incidence of complications. The techniques used in managing sickle-cell disease patients with SAH are discussed. PMID- 1885974 TI - Radiation-induced meningiomas: experience at the Mount Sinai Hospital and review of the literature. AB - From the records of The Mount Sinai Hospital, seven cases which met established criteria for radiation-induced meningiomas were identified. This represents the largest series of radiogenic meningiomas documented in North America and includes both intracranial and intraspinal tumors. The records and pathological specimens were reviewed and these data analyzed with other cases retrieved from the world literature. This study reveals that radiation-induced meningiomas can be categorized into three groups based on the amount of radiation administered: 1) low dose; 2) moderate dose and miscellaneous; and 3) high dose. The overwhelming majority of cases had received low-dose irradiation (800 rad) to the scalp for tinea capitis and the second largest group resulted from high-dose irradiation for primary brain tumors (greater than 2000 rad). The unique features distinguishing radiation-induced meningiomas from other meningiomas are reviewed. Although histologically atypical tumors were common in this series, overt malignancy was not encountered. The preoperative management of these lesions should include angiography to evaluate for large-vessel occlusive vasculopathy, a known association of meningiomas induced by high-dose irradiation. Given the propensity these tumors possess for recurrence, a wide bony and dural margin is recommended at surgical resection. PMID- 1885975 TI - Medulloblastoma: freedom from relapse longer than 8 years--a therapeutic cure? AB - Seventy-seven patients presenting with medulloblastoma between 1958 and 1986 were treated at Stanford University Medical Center and studied retrospectively. Multimodality therapy utilized surgical extirpation followed by megavoltage irradiation. In 15 cases chemotherapy was used as adjunctive treatment. The 10- and 15-year actuarial survival rates were both 41% with an 18-year maximum follow up period (median 4.75 years). There were no treatment failures after 8 years of tumor-free survival. Gross total removal of tumor was achieved in 22 patients (32%); the surgical mortality rate was 3.9%. No significant difference was noted in the incidence of metastatic disease between shunted and nonshunted patients. The classical form of medulloblastoma was present in 67% of cases while the desmoplastic subtype was found in 16%. Survival rates were best for patients presenting after 1970, for those with desmoplastic tumors, and for patients receiving high-dose irradiation (greater than or equal to 5000 cGy) to the posterior fossa. Although early data on freedom from relapse suggested a possible beneficial effect from chemotherapy, long-term follow-up results showed no advantage from this modality of treatment. The patterns of relapse and survival were examined; 64% of relapses occurred within the central nervous system, and Collins' rule was applicable in 83% of cases beyond the period of risk. Although patients treated for recurrent disease could be palliated, none were long-term survivors. The study data indicate that freedom from relapse beyond 8 years from diagnosis can be considered as a cure in this disease. Long-term follow-up monitoring is essential to determine efficacy of treatment and to assess survival patterns accurately. PMID- 1885976 TI - Symptomatic subependymoma: a clinicopathological and flow cytometric study. AB - Twenty-one intracranial subependymomas were reviewed with regard to presentation, diagnosis, operative findings, and long-term follow-up data. The histopathological features were critically reviewed, and deoxyribunucleic acid analysis was performed by flow cytometry. The patients' mean age was 48.5 years (range 32 to 72 years). In 14 cases the tumor was located in the fourth ventricle, in six within a lateral ventricle, and in one in the third ventricle with extension into the lateral ventricle. Radiographic characteristics included isodensity with minimal enhancement on computerized tomography, frequent dystrophic calcification, and isointensity on T1-weighted or slight hyperintensity on T2-weighted magnetic resonance images. The predominant histological features in all cases were those of classic subependymoma. Nonetheless, pathological examination showed a minor (less than 20%) ependymoma component in five cases, significant cytological atypia in seven, mitoses in 11, endothelial prominence in four, and focal hemorrhage-associated necrosis in two. Flow cytometry revealed a diploid pattern in 12 patients, tetraploidy in two, and aneuploidy in one. Two patients died in the perioperative period. Of the remaining 19, 12 underwent gross total resection (two of whom received postoperative irradiation) and seven underwent subtotal resection (five of whom received irradiation). None of the 12 non-irradiated patients developed tumor progression or died of direct tumor-related causes. Of the seven irradiated patients, follow-up imaging studies demonstrated their tumors to be radioresponsive, particularly with doses of 5000 cGy or greater. Despite the presence of cytological atypia and mitotic activity in the majority of cases, the prognostic effects of such factors as tumor location and the extent of surgical resection outweighed those of the standard histopathological parameters. Routine postoperative irradiation is not recommended, but should be reserved for cases with a symptomatic residual or recurrent subependymomas following surgery. PMID- 1885977 TI - "Angioglioma" and the arteriovenous malformation-glioma association. AB - The term "angioglioma" denotes a highly vascular glioma, most of which are low grade lesions associated with a favorable prognosis. The authors encountered an example of this pathology, a cystic oligodendroglioma associated with prominent vasculature which both clinically and histologically mimicked an occult arteriovenous malformation (AVM). This case and reports of the association of AVM and glioma prompted a histological review of 1034 surgically resected AVM's, both angiographically occult and visible, among which no oligodendroglial or astrocytic forms of "angioglioma" were found. Eight cases were observed, however, wherein oligodendroglial cells were increased in number within or about the malformation. Two basic histological patterns of oligodendroglial cell excess were seen; one appeared to be malformative in nature with abnormal disposition of oligodendroglial cells being an integral part of the AVM, whereas in the other an apparent increase in cellularity seemed the result of chronic ischemia with condensation of white matter. It appeared that the areas of increased oligodendrocyte content seen in association with AVM are non-neoplastic lesions that exhibit two rather distinct histological patterns of differing origin. In an effort to determine the frequency of "angioglioma," the authors examined Tissue Registry data for several glioma groups in which highly vascular examples are prone to occur. Tumors selected for study included 104 cerebellar-type (pilocytic) astrocytomas, 82 oligodendrogliomas, and 51 supratentorial pilocytic astrocytomas. Histological hypervascularity mimicking a vascular malformation (that is, an "angioglioma") was encountered in 5%, 4%, and 12% of the cases, respectively. Based upon clinical, radiological, and pathological reviews of these cases, as well as a careful review of the literature, it was concluded that 1) "angiogliomas" are neither rare nor represent a distinct clinicopathological entity; 2) in histological but not necessarily angiographic surgical terms, they represent simply highly vascular gliomas, usually of low grade; and 3) the clinicopathological and angiographic features as well as the prognosis of such lesions do not differ from those of similar gliomas without angioma-like vasculature. Finally, "angiogliomas" must not be confused with gliomas of high grade malignancy which, due to neovascularity, may be highly vascular at angiography and at surgery. PMID- 1885978 TI - Induction of transformational changes in normal endothelial cells by cultured human astrocytoma cells. AB - Endothelial cell proliferation is a significant biological feature of malignant astrocytomas. The ability of the cells of these tumors to elaborate mitogenic angiogenesis factors has been well documented. However, less is known about the transformational effects that neoplastic astrocytes may have on the endothelial cells within malignant astrocytomas. In this study, the hypothesis that humoral factors elaborated by cells derived from malignant astrocytomas induce transformational changes in normal endothelial cells in vitro is investigated. Conditioned medium (CM) was prepared from exponentially growing cultures of a human glioblastoma cell line (UW18) and from two rat brain-tumor cell lines: an anaplastic astrocytoma (R175A) and a glioblastoma with sarcomatous elements (9L). Subconfluent target bovine aortic arch endothelial cells (BAEC's) were exposed for 48 hours to varying concentrations of CM prepared from each of these tumors, and then evaluated for transformational changes. Different molecular weight (MW) fractions of UW18 CM were prepared by molecular ultrafiltration, and each fraction was tested for transforming activity. Transformation endpoints included changes in cellular deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) content and distribution (measured by differential flow cytometry) and changes in de novo DNA synthesis determined by 3H-thymidine incorporation. Significant changes in the amount and distribution of DNA and RNA were observed in the BAEC's treated with UW18 CM compared to untreated BAEC's. At 10% concentrations of UW18 CM, changes in the RNA profile of target BAEC's were evident, and at 30% concentrations of UW18 CM, an irregular bimodal distribution was well established. Patterns of DNA were also altered in a concentration-dependent manner, with significant aneuploidy developing at UW18 CM concentrations of 20%. The DNA synthesis in BAEC's increased with increasing CM concentrations, up to a maximum of about 250% of control values at 30% concentrations of UW18 CM. The transformational changes induced after exposure of BAEC's to CM prepared from R175A and 9L were significantly less than those observed with UW18 CM. Molecular ultrafiltration was used to prepare UW18 CM fractions with MW cutoffs of less than 10 kD, 10 to 30 kD, and greater than 30 kD. Transformational activity was significant only in CM's with an MW of 10 to 30 kD. It is concluded that the UW18 human glioblastoma cell line elaborates a soluble factor, or group of factors, with an MW in the 10- to 30-kD range, capable of inducing transformational alterations in target normal endothelial cells, and that such transformation may account for some of the abnormal endothelial cell changes associated with malignant astrocytomas. PMID- 1885979 TI - Treatment of vasospasm with a 480-nm pulsed-dye laser. AB - Laser energy at a wavelength of 480 nm was applied in 1-microseconds pulses of 3 to 10 mJ to two models of vasospasm. Rabbit common carotid arteries (CCA's) were constricted chronically by the application of human blood within a silicone sheath. Peak vasospasm developed 24 to 48 hours later, and persisted for up to 6 days. Endovascular laser treatment was delivered to 40 CCA's via a 200-microns diameter silica quartz fiber introduced through the femoral artery. The CCA caliber increased from 60% of the pre-vasospasm control diameter to a minimum post-laser diameter of 83% of control. No instances of laser-induced perforation or of arterial thrombosis were observed for up to 60 days after treatment. Prophylactic laser application to nine normal vessels was able to attenuate the development of vasospasm if blood was applied immediately thereafter (88% vs. 59% of control diameter, p less than 0.02), but not if blood was applied 7 days later. Studies in 16 normal CCA's established that there was a considerable margin between the laser energy required to induce dilatation and that which caused perforation, providing that the fiber remained relatively central within the artery. Morphological examination demonstrated focal loss of endothelial cells immediately after laser application, followed approximately 7 days later by the development of areas of intimal hyperplasia. Only minimal changes were observed in the medial or adventitial layers. In a second study, the basilar artery of seven dogs was constricted chronically by two intracisternal injections of autologous blood 3 days apart. Five dogs received endovascular laser treatment 7 or 10 days after the first injection, when basilar artery diameter was reduced to a mean of 61% and 77% of control, respectively. Immediately following treatment, basilar artery diameter increased to 104% and 102% of resting diameter, respectively. Both untreated and laser-treated arteries were smaller than the control diameter at 30 days (80% and 82%, respectively), but in each group the vasodilatory response to hypercapnia was preserved. These findings indicate that 1-microsecond laser pulses are well tolerated by systemic and cerebral arteries in two different animal models, and suggest that the 480-nm pulsed-dye laser may have an application for the treatment or prophylaxis of cerebral vasospasm. PMID- 1885980 TI - Reduction of central nervous system ischemic injury by monoclonal antibody to intercellular adhesion molecule. AB - Activated leukocytes appear to be directly involved in potentiating ischemic central nervous system (CNS) injury. Adhesion of leukocytes to endothelium is essential for their migration and requires the binding of adhesion receptors of the leukocyte (CD 18) to an intercellular adhesion molecule (ICAM) on endothelium. Monoclonal antibodies to an ICAM can block leukocyte adhesion and transendothelial migration. To determine the efficacy of anti-ICAM antibody treatment in preserving neurological function after CNS ischemia, two animal models were used. A 1-mg/kg dose of anti-ICAM was given to rabbits 30 minutes before induction of ischemia either in the spinal cord using temporary aortic occlusion or in the brain using intra-arterial microspheres. In this study, treatment with anti-ICAM produced a significant reduction in neurological deficits in the reversible spinal cord ischemia model but not in the irreversible brain ischemia model. This protective effect supports the active role of leukocytes in CNS reperfusion ischemic injury and offers potential for future therapy. PMID- 1885981 TI - Spontaneous dissecting aneurysms of the basilar artery presenting with a subarachnoid hemorrhage. Report of two cases. AB - A spontaneous dissecting aneurysm of the basilar artery is a rare disorder, usually presenting with ischemia rather than a subarachnoid hemorrhage (SAH). Two cases are described of a dissecting aneurysm of the basilar artery presenting with an SAH. Vertebral angiography revealed a double lumen to the basilar artery. Magnetic resonance (MR) imaging detected the intramural hematoma. One patient was treated conservatively, and the other underwent operative intervention with wrapping of the aneurysm. The usefulness of MR imaging in the diagnosis and the treatment options are discussed. PMID- 1885982 TI - Curative treatment of scalp arteriovenous fistulas by direct puncture and embolization with absolute alcohol. Report of three cases. AB - Three cases of direct arteriovenous fistulas of the scalp (two involving cirsoid aneurysms) are presented. All three patients were treated with direct puncture of the venous pouch and injection of absolute ethyl alcohol during compression of the venous outflow of the fistula. Two of the three patients were cured with this treatment alone. The third patient, with a very high-flow giant fistula, required injection of glue to close the fistula and subsequent surgical extirpation of the resulting hard mass lesion. PMID- 1885983 TI - Sixth nerve schwannomas. Report of two cases. AB - Two cases of sixth cranial nerve schwannoma are presented with a review of four other cases from the literature. The clinical spectrum, neuroradiological findings, and surgical outcome of the six cases are discussed. There are two distinct clinical presentations for sixth cranial nerve schwannomas. Type I sixth nerve schwannomas present with sixth nerve palsy and diplopia and arise from the cavernous sinus. In contrast, type II sixth nerve schwannomas have a more severe presentation with obstructive hydrocephalus, raised intracranial pressure, sixth nerve palsy, and diplopia. This type arises along the course of the sixth cranial nerve in the prepontine area. Cavernous sinus involvement in either type may preclude total surgical excision and indicate an increase possibility for recurrence. PMID- 1885985 TI - Successful excision of a juvenile-type spinal arteriovenous malformation following intraoperative embolization. Case report. AB - The case of a 57-year-old woman with a 14-year history of progressive paraparesis is presented. Selective spinal angiography revealed a juvenile-type spinal arteriovenous malformation (AVM) with a typical large size and rapid flow. The AVM was located primarily in the retromedullary space at the cervicothoracic junction. The AVM was successfully obliterated by intraoperative embolization using isobutyl-2-cyanoacrylate and surgical excision. PMID- 1885984 TI - Gliofibroma. Case report. AB - The case history of an infant with a large gliofibroma is presented. Gliofibromas are rare mixed glialmesenchymal tumors that have been poorly characterized. The computerized tomography appearance and a detailed light and electron microscopic description are presented, along with immunoperoxidase studies of this tumor. This case is compared with gliofibromas described elsewhere in the literature. PMID- 1885986 TI - Sciatic nerve entrapment in a child. Case report. AB - A child was brought for evaluation of signs of unilateral chronic progressive sciatic nerve dysfunction found to be due to nerve entrapment in the thigh by a fibrovascular band. Sectioning of the band was followed by marked improvement in the nerve function. Compression by a band is a rare but treatable cause of sciatic neuropathy. PMID- 1885987 TI - Embolization of arteriovenous malformations with peripheral aneurysms using ethylene vinyl alcohol copolymer. Report of three cases. AB - The authors report three cases of arteriovenous malformations (AVM's) with aneurysms arising from the feeding artery; all were successfully treated with a new nonadhesive liquid embolic material, ethylene vinyl alcohol copolymer (EVAL). In two patients the AVM's were totally removed without difficulty, and in one the AVM was managed conservatively after embolization. No new neurological deficits appeared during or after embolization. After road-mapping techniques, EVAL was injected slowly until the feeding artery and aneurysm were completely obliterated. This embolic agent is easy to handle and is considered safe compared with other adhesive liquid embolic agents, such as isobutyl-2-cyanoacrylate or n butyl cyanoacrylate. It is concluded that EVAL is an excellent agent for embolizing an AVM with a peripheral aneurysm on the feeding artery. PMID- 1885988 TI - The use of an intraluminal shunt for bypass grafts of the cavernous internal carotid artery. Technical note. AB - The authors describe an indwelling intraluminal shunt for use during graft bypass procedures of the cavernous internal carotid artery. The clinical use of this shunt in a patient with meningioma invading the right cavernous sinus is described. This shunt has also been found applicable during carotid endarterectomy, and should prove to be a useful addition to the neurosurgical armamentarium for skull-base surgery. PMID- 1885989 TI - Thalamotomy lesions. PMID- 1885990 TI - Epidural lipomatosis. PMID- 1885991 TI - Hangman's fracture vs. hanged-man's fracture. PMID- 1885992 TI - Differentiation of epithelial cysts. PMID- 1885993 TI - Fusiform aneurysm after surgery for craniopharyngioma. PMID- 1885995 TI - Large-area plan-view sample preparation for GaAs-based systems grown by molecular beam epitaxy. AB - We describe a method for plan-view transmission electron microscopy (TEM) sample preparation that takes advantage of extreme etch-rate selectivity in GaAs and AlAs in HF/H2O solutions. GaAs/InxGa1-xAs/GaAs strained-layer films (x = 0.05, 0.10, 0.19, 0.22) were chemically lifted off using this technique and were mounted on Cu TEM grids such that TEM transparent areas of up to 1 x 2 mm of constant thickness (196.4 nm) could be viewed. This simple, large-area plan-view technique uses only chemical methods and significantly extends the usefulness of TEM for the evaluation of crystal quality in GaAs-based epitaxial systems. The method requires the growth of a release layer of AlAs (10 nm thick) prior to the layered structure of interest. PMID- 1885994 TI - Effects of substrate texture and curvature on the morphology of cultured cells. AB - The ultrastructural characteristics of several growth matrices were examined using two cell types chosen for their distinct growth habits. Chinese hamster ovary cells and Balb-c 3T3 mouse fibroblasts were grown on flat substrates (glass, tissue culture plastic, Millipore filters) as well as spherical (glass, tissue culture plastic, cross-linked dextran) substrates. Cells were plated maintaining equal densities and growth surface area. Once the majority of the cells reached confluency, the cell's morphology on each matrix was examined using scanning electron microscopy. Digital analysis was performed on cell attachment area to compare the effect of each matrix on cell spreading. Variation in cell shape was dramatic between matrices, being most noticeable between a textured surface (filter, dextran bead) and that of a smooth (glass) surface. Even within smooth surfaces, some variation was observed. There was also an effect of matrix curvature on cell attachment area, the greatest being in the 3T3-c Balb cells, causing an overall decrease in the area of attachment between cell and matrix. The changes seen could also be related to the particular cell type used. Hamster ovary cells tended to be cylindrical and showed little effect between matrices, whereas the mouse fibroblasts, which are more flattened, showed the matrix effect to a greater degree. This study demonstrates the necessity of being aware of substrate-induced cell changes in tissue culture, where some variation in cell shape may be due to the surface on which the cells are grown as opposed to the experimental procedure. PMID- 1885997 TI - Electron crystallography at atomic resolution: the structure of the odd-chain paraffin n-tritriacontane. AB - The crystal structure of the odd-chain paraffin, n-tritriacontane, nC33H68, is determined directly by using low-dose electron microscope images and electron diffraction intensity data from epitaxially grown microcrystals. Phases of the most intense "polyethylene" reflections are determined from triplet structure invariant relationships often used in X-ray crystallography. Low-dose electron microscopic images provide phases of the low-angle "lamellar" reflections and these can be used with one-dimensional structure-invariant relationships to determine other phases on the 00l reciprocal row. The phase set is sufficient to calculate an electrostatic potential map which is directly interpretable as a structure image at atomic resolution. PMID- 1885996 TI - Immunogold labelling of the intermediate filament-lamina-nuclear matrix system in HeLa and BHK-21 cells. AB - Whole-mount, sequentially extracted cells combined with immunogold electron microscopy were developed to demonstrate the intermediate filaments, lamina, and nuclear matrix (IF-L-NM) and to identify their protein components. The IFs of HeLa cells were reacted both with keratin and vimentin monoclonal antibodies; meanwhile, the IF network of BHK-21 cell was reacted only with vimentin monoclonal antibody. The lamina and nuclear matrices of both HeLa and BHK-21 cell were labelled, respectively, with lamin monoclonal antibody-gold complex and 280 Kd nuclear matrix protein monoclonal antibody-gold complex. The monoclonal antibody to keratin could cross-react with the lamina both of HeLa and BHK-21 cells. PMID- 1885998 TI - Cellular location of thymus-leukemia (TL) antigen as shown by immuno cryoultramicrotomy. AB - Thymus-leukemia (TL) antigen is a class I molecule of the major histocompatibility complex that is expressed on the surface of mouse cortical thymocytes. Though not expected, it has been reported that TL antigen can be found on isolated mitochondria of TL+ cells. We used immuno-cryoultramicrotomy to look for TL on mitochondria in situ, thereby avoiding the plasma membrane contamination that occurs when isolating organelles. Establishing optimal fixation conditions was crucial, as mitochondrial structure was not preserved by the low concentrations of fixative needed for detection of antibody labeling. The plasma membranes of tissue culture and thymus cells were labeled well with anti TL antibody and protein A-gold conjugate, while mitochondria within the cells were not labeled. Isolation of mitochondria on a one-step Ficoll gradient resulted in a purer organelle preparation than did isolation of mitochondria by centrifugation alone. Generally, mitchondria within this purer preparation were not labeled. Our data show that under conditions where contamination by plasma membrane is not a major concern, TL antigen cannot be detected on mitochondria. PMID- 1885999 TI - Loss of grain boundary segregant during ion milling. AB - It is shown that material segregated to grain boundaries can be lost during ion milling. This specimen preparation artifact has been studied in the case of bismuth in copper and has also been observed for phosphorus in stainless steel. The loss is associated with specimen heating during ion milling and can be alleviated by good clamping and cooling of the specimen during milling. Specimen heating permits grain boundary diffusion of the segregating element to the specimen surfaces with subsequent loss of segregant from the specimen by evaporation or sputtering during ion milling. Loss of bismuth during in situ heating to 200-300 degrees C is demonstrated. Therefore, care must be taken in specimen preparation for analytical electron microscopy measurement of such segregation. Similar effects may occur during ion milling of other materials, especially those where low thermal conductivity will result in high beam heating. In these cases, care must be taken to avoid loss of segregant during specimen preparation. Additional tests showed that no significant loss of segregant was observed during X-ray microanalysis, even at nominal room temperature and probe currents five-fold higher than that normally used for microanalysis. PMID- 1886000 TI - A rapid method for the preparation of yeast for immunoelectron microscopy using Lowicryl HM-20. AB - We describe a fixation and embedding procedure for the yeast Saccharomyces cerevisiae using Lowicryl HM-20 which is rapid, gives excellent fixation, and avoids the low temperature handling normally associated with embedding in this resin. This procedure yields superior structural preservation when compared to the commonly used rapid embedding procedure which employs Lowicryl K4M. We demonstrate that sections prepared using our rapid procedure are suitable for use in immunogold labelling experiments. PMID- 1886001 TI - The effect of aluminum coating on elemental standards in X-ray microanalysis. AB - The standardisation of frozen hydrated bulk biological specimens using gelatin standards is described. The relationship between corrected elemental X-ray counts and ionic concentration was found to be linear, and minimum detectable limits for each element are stated. Variations in uncorrected standard curves were found to be due to changes in aluminium coating thickness. There was an inverse relationship between coating thickness and elemental X-ray counts. The factors causing this are discussed. To avoid errors arising from inconsistent aluminium thickness, experimental material should only be compared with standards of similar aluminium net counts. This can be achieved most easily by mounting and analysing specimen and standard together. PMID- 1886002 TI - Immunoelectron localization of mitochondrial F1 factor in cryosections of heart muscle cells. AB - Immunocytochemistry was used to investigate the localization of F1 ATPase in mitochondria of cryosections of adult mouse heart muscle cells. The initial aldehyde fixation was the only denaturation step for antigens. The fine structure was preserved with contrast enhancement as the sections were maintained hydrated, with the advantage that the entire procedure is completed in one working day. The reaction was highly specific, and entire mitochondria were labeled with the Protein A-gold complex. A new analytical technique, electron spectroscopic imaging (ESI), contributed to a better visualization of the localization of the F1 factor. PMID- 1886003 TI - A glass apparatus for the preparation of freeze-dried samples for SEM. PMID- 1886004 TI - Methods of onion seed preparation for scanning electron microscope studies of the seed coat. PMID- 1886005 TI - A fast, simple method for preparing flat semi-thin sections from epoxy embedded materials. PMID- 1886006 TI - Ultrastructural cryoimmunocytochemistry is a convenient tool for the study of DNA replication in cultured cells. AB - In the present study, we have optimized an immunocytochemical ultrastructural approach for in situ localization of newly synthesized DNA in unsynchronized as well as in synchronized human HeLa cells and in exponentially growing mouse P815 cells, which had incorporated bromodeoxyuridine (BrdU) during short pulses varying from 1 to 20 minutes. The incorporated BrdU was detected in hydrolyzed ultrathin cryosections or Lowicryl sections by means of a monoclonal antibody, revealed by secondary colloidal gold-labeled probes. The results demonstrate our ability to study, with high resolution and reproducibility, DNA replication during consecutive periods of the S-phase, which is monitored by the incorporation of tritiated thymidine. In addition, this approach allows one to perform a concomitant mapping of replicated DNA and various enzymes of the replisome. PMID- 1886007 TI - Absorption and multiple scattering by suspensions of aligned red blood cells. AB - The analytical theory of multiple scattering [J. Opt. Soc. Am. 60, 1084 (1970)] permits predictions of scattering patterns by homogeneous suspensions of aligned and randomly oriented particles. Predictions for randomly oriented particles have been tested previously. Using an optical system involving a He-Ne laser and suspensions of red blood cells, we tested the theory's predictions for scattering by suspensions in two distinct alignments. The qualitative effects of cell alignment on light scattering are consistent with those predicted, although measured differences in scattering between the two alignments exceed those predicted. We conclude that the theory may provide an optical means of distinguishing particle orientation in multiple scattering suspensions. PMID- 1886008 TI - Perceived speed and direction of complex gratings and plaids. AB - Measurements of perceived speed were obtained for a variety of drifting simple and complex gratings, and measurements of perceived speed and direction were obtained for plaids. For sine gratings, perceived speed falls off at high spatial frequencies, the effect of spatial frequency being greatest at high speeds. Speed matches obtained from a variety of one-dimensional complex gratings are in some cases consistent with a simple averaging of the discrepant speeds signaled by their spatial Fourier components when seen alone. However, in other cases the results do not fit such an interpretation but suggest the involvement of a mechanism other than Fourier decomposition and recombination. Measurements of the perceived speed of plaids suggest that the observed spatial-frequency-dependent variations in encoded speed of gratings arise largely at a low level, before the aperture problem is solved. Measurements of the perceived direction of plaids whose components are of different spatial frequencies and hence have different perceived speeds show large deviations from the direction predicted by the intersection-of-velocity-constraints model [Nature 300, 523 (1982)] and are suggestive of a revised two-stage model in which the computation of pattern direction is based on the (sometimes disparate) perceived speeds of the components rather than their actual speeds. PMID- 1886009 TI - Dynamics of adaptation for vision with a stabilized image. AB - The addition of a uniform increment of light to a high-contrast image that has been stabilized on the retina reveals marked perceptual nonlinearities. When the increment is small, the pattern appears in its original phase (OP), large increments produce an apparent phase reversal (APR), and intermediate increments may yield an apparently blank field or an oscillation of the apparent phase. In the present series of studies the threshold values used to produce a stable OP and APR were determined as a function of adaptation time before the application of the increment. The stabilized target had a luminance profile consisting of the difference of two Gaussians. A model of detection incorporating a multiplicative gain controlled by a filtered version of the stimulus was used to account for the occurrence of the OP and the APR and the transitory phenomena following the uniform increment. It is argued that the midpoint of the transition zone between the OP and APR, corresponding to blanking, enables us to estimate the shape of the step response function of the gain filter independently of the subsequent detection processes. PMID- 1886011 TI - The management of traumatic scalp injuries: report of cases. PMID- 1886010 TI - Multiple nodules of the lip, cheeks, and tongue. PMID- 1886012 TI - Cherubism in a patient with Noonan syndrome: report of a case. PMID- 1886013 TI - Hemangioma of the frontal bone: review of the literature and report of a case. PMID- 1886014 TI - A method to accurately determine the preinjury intercanthal distance. PMID- 1886015 TI - New appliance for repositioning the proximal segment during rigid fixation of the sagittal split ramus osteotomy. PMID- 1886016 TI - Wires vs screws for management of mandibular fractures. PMID- 1886017 TI - Manual separation of the pterygomaxillary suture. PMID- 1886018 TI - Treatment of rhinophyma with the carbon dioxide laser. PMID- 1886019 TI - Sparking from ceramic brackets. PMID- 1886020 TI - Know thy roots. PMID- 1886021 TI - Recovery of mandibular mobility following orthognathic surgery. AB - The aim of this prospective study was to define the patterns of recovery of mandibular mobility following three commonly performed orthognathic surgical procedures. Twenty-two consecutive patients undergoing either isolated Le Fort I osteotomy (LE FORT; n = 7), sagittal split ramus osteotomies (SSRO; n = 7), or intraoral vertical ramus osteotomies (IVRO; n = 9) were studied. LE FORT and SSRO patients had no mandibular immobilization, whereas IVRO patients were immobilized by dental fixation for 3 weeks. Mandibular mobility was assessed by measurement of maximal mandibular opening (MMO) and lateral and protrusive excursions. No significant difference in MMO was observed between groups prior to surgery (LE FORT, 47.0 mm; SSRO, 50.7 mm; IVRO, 54.5 mm). A significant reduction in MMO occurred immediately after surgery in the LE FORT and SSRO groups and at release of fixation in the IVRO group. Each group returned to presurgical levels of mandibular mobility at a different rate following surgery. LE FORT patients recovered quickly, regaining 83% (mean, 38.7 mm) of MMO by 1 month and exceeded preoperative levels (mean, 49.6 mm) by 6 months. SSRO patients showed hypomobility (mean, 23.5 mm) after 1 month, with significant improvement in MMO (mean, 38.0 mm) at 2 months, and nearly complete recovery (96.2%; mean, 48.8 mm) at 6 months. IVRO patients recovered rapidly after release of dental fixation, achieving 78% (mean, 39.8 mm) of preoperative MMO at 2 months. This study shows that significant differences in recovery patterns of mandibular mobility exist between surgical procedures. The clinician should be aware of these differences in recovery patterns in defining goals for individual patient rehabilitation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1886022 TI - The effect of a chlorhexidine rinse on the incidence of alveolar osteitis following the surgical removal of impacted mandibular third molars. AB - A prospective randomized double-blind placebo-controlled study was conducted with 139 patients (278 bilaterally impacted mandibular third molars) to determine the effect of a perioperative 0.12% chlorhexidine gluconate rinse on the incidence of alveolar osteitis following surgical removal of impacted mandibular third molars. A statistically significant 60% reduction in the incidence of alveolar osteitis was obtained in the chlorhexidine group compared with the placebo group. In most subgroups analyzed, chlorhexidine was associated with at least a 50% reduction in alveolar osteitis compared with control groups. PMID- 1886023 TI - Rhinoplasty: contemporary management of the nasal tip. AB - Surgical management of the nasal tip in esthetic rhinoplasty has long proved to be a challenging and frustrating task. While standard reductive tip techniques work well in many cases, there are those cases that require augmentation to yield an ideal cosmetic result. In this article, both reductive as well as augmentation techniques are presented to illustrate the advantages of each treatment. PMID- 1886024 TI - What are normal esthetic values? AB - The management of dentofacial deformities is at least partially assessed on the basis of standardized radiographs and photographs, which are analyzed according to accepted norms. Although one frequently hears the cry of "Treat the patient, not the cephalometric radiograph," with the development of sophisticated computer assisted digitizing systems and cephalometric analysis programs, there may be a greater reliance on cephalometric and photometric norms than previously. If we are to become more dependent on these normal values, it is necessary to know their origin and significance. PMID- 1886025 TI - Peripheral ameloblastoma: a clinical and histologic study of 11 cases. AB - Peripheral ameloblastoma (PA) is a rare odontogenic tumor. Previously, only 39 cases of PA had been reported in the English literature. In this article 11 additional cases of PA are presented. Concordance with previous cases was evident with regard to race, clinical appearance, and site of predilection. However, differences were observed with regard to age, sex distribution, and predominant histologic pattern. The average age in the current cases is younger, there is no male bias, and the most common histologic pattern is plexiform rather than follicular or acanthomatous. Recurrence following simple excision is rare, but has been reported. Long-term postoperative follow-up is recommended. PMID- 1886026 TI - An epidemiologic and anatomic survey of odontogenic infections. AB - An 81-month review of patients with infections of odontogenic origin admitted to the oral and maxillofacial surgery service at a county hospital and teaching facility in northeast Ohio is presented. Age, sex, race, etiology, pathogens isolated, admission temperature, and admission white blood cell count were identified and related to the anatomic space(s) encountered. Multispace and single-space infections occurred with equal distribution. In both the multispace and single-space infections, the submandibular and buccal spaces were most frequently involved. Males were affected with single-space infections twice as often as females. An equal distribution among sexes was found in multispace infections. The most common age range for all infections was 25 to 30 years. alpha-Hemolytic streptococci, Bacteroides melaninogenicus, and beta-hemolytic streptococci were the most frequently isolated pathogens. Third molars were the prevalent cause in both multispace and single-space infections that required hospital admission. PMID- 1886027 TI - Histomorphometric study of trabecular bone remodeling during condylar process fracture healing in the growing period: experimental study. AB - Trabecular bone remodeling during condylar fracture healing in the growing period was analyzed by histomorphometry with a synchronous system. Data from the study showed displacement of the fractured condyle was compensated by the changes in remodeling ascribed to the pubertal spurt of growth, and that such remodeling still continued even after clinical healing. The regional acceleratory phenomenon, evolved to potentiate tissue healing, was observed 1 week after induction of the fracture. Mesenchymal cells were presumably modulated into chondroblasts that promoted endochondral ossification. It was concluded that trabecular bone remodeling plays an important role in healing of condylar fractures during the growth period. PMID- 1886028 TI - Comparison of absorbable self-reinforced poly-L-lactide screws and metallic screws in the fixation of mandibular condyle osteotomies: an experimental study in sheep. AB - Nine osteotomies of the neck of the mandibular condylar process in sheep were fixed with self-reinforced poly-L-lactide screws and nine with metallic screws; two osteotomies were left unfixed. Radiographic examination was carried out at 3 weeks. The animals were killed at 6, 12, and 24 weeks. Malalignment was detected at 3 and 12 weeks in both unfixed condyles. The consolidation of the fixed osteotomies seemed to be faster in the polylactide group than in the metallic group. There were no complications in the healing of the fixed osteotomies. PMID- 1886029 TI - [Psychological states and personality as factors in the morbidity of head and neck malignant tumors]. AB - Many publications have repeatedly indicated that there seems to be a correlation between neoplastic disease and certain types of psychological situations. However, such studies subjected malignant tumors in head and neck region are scanty so far. We applied Cornell Medical Index Health Questionnaire (CMI) and Maudsley Personality Inventory (MPI) to collect medical and psychiatric data from 86 patients (56 males and 30 females) with head and neck malignant tumors and 115 control patients (73 males and 42 females) with head and neck diseases other than malignant tumors. Analysis of CMI data using Diagnostic Sheet, Fukamachi's method and Modification of Abe's method, and analysis of each of Extroversion Introversion scale scores, Neuroticism scale scores and Lie scale scores of MPI led the following conclusion. 1) Both male and female patients with head and neck malignant tumors showed to be more depressive than their control patients were. Especially, between the two patient groups in males, there was a statistically significant (p less than 0.05) difference. 2) Regarding neurosis, autonomic nerve dysfunctioning and extroversion-introversion, none of these factors seemed to be related with the morbidity of head and neck malignant tumors. Further exploration of this issue, with a special attention to the relationship between depression and head and neck malignancy should be conducted, if possibly, from a prospective point of view. PMID- 1886030 TI - [Histological study on gland tissue in the median region of the lingual root- morphology of the foramen cecum and posterior lingual gland]. AB - The lingual root is an area where the thyroid gland develops and small salivary glands composed of both serous and mucous glands are distributed in the submucosa. In this paper the foramen cecum and mucous glands at the root of the tongue were histologically investigated in serial sagittal sections of the medial portion of the lingual root. The materials were obtained from 59 autopsied cases, excluding the cases with metabolic disease, brain tumor and neck tumor in whom the original disease might exert direct or indirect effects to the gland tissue. The frontal end was determined to be the line which connects the right and left palatoglossal arch junctions with the tongue, and the rear end the line of transition of the vallecula to the epiglottis. The specimen was cut in half along the median lingual sulcus and median glossoepiglottic fold. Each serial section of 4 microns in thickness was cut from the median plain to the lateral and stained with Hematoxylin-Eosin or Pas-Alcian blue at pH 2.5. The results of the study were summarized as follows. 1) The foramen cecum was histopathologically confirmed in 12 cases out of 59 (20%). The ratio of the detection did not show any difference between both sexes and in the groups of different age. 2) The mucous gland opening into the mucosal epithelium, which were located at the side of the lingual apex from the Ebner's gland or serous gland, were detected in 45 out of 59 (76%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1886032 TI - [Experimental middle ear cholesteatoma originated from free skin graft of the external ear]. AB - The pathogenesis of middle ear cholesteatoma has been thought to be invasion of squamous epithelium originated from the external ear skin including the tympanic membrane. There is no evidence, however, that the external ear skin has more potential to form cholesteatoma than that of other sites. In this report experimental middle ear cholesteatoma of guinea pigs originated from the external ear skin was histologically compared with that originated from the auricular skin. Cholesteatoma as dermal cyst was seen in the middle ear of almost all animals (25/28 = 89.3%), using a free skin graft (3 x 3 mm), regardless of the skin taken from superior (group A) or inferior (group B) part of the external ear, or the auricle (group C) eight weeks after skin implantation. The activity of epithelium such as keratinization was evident in group C. There is, however, no obvious difference in surrounding granulation tissues among group A, B, and C. In a half of this series, cyst wall was broken and its contents (debris) mainly consisted of keratin were put on surrounding granulation tissues three weeks after skin implantation. Striking keratinized epithelium and subepithelial inflammations in relation to the amount of debris were observed at the eighth week. These findings suggest that the external ear skin does not have specific potential to form cholesteatoma and keratin plays some roles in growth of cholesteatoma. PMID- 1886031 TI - [Study on eosinophil cationic protein (ECP) and arylsulfatase B in nasal secretions and sera from patients with nasal allergy]. AB - Recently four tissue toxic proteins namely major basic protein (MBP), eosinophil peroxidase (EPO), eosinophil-derived neurotoxin (EDN), and eosinophil cationic protein (ECP) were found in eosinophilic leucocytes. Although the characteristics of these proteins concerning tissue damage in the local site of type I allergic reaction have been investigated mainly in lower respiratory tract, the actual clinico-pathological roles of these proteins in nasal allergy are not clarified. Contrary, eosinophils also have histaminase, arylsulfatase, phospholipase D, which are considered to act on a negative feedback mechanism in allergic reaction through inactivation of chemical mediators. Therefore, estimation of ECP and simultaneously arylsulfatase B in nasal secretion and the sera from patients with nasal allergy may clarify the dynamics of clinico-pathological state, especially in the late phase of allergic reaction in each patients. ECP concentrations in the nasal secretions from 22 patients and in the sera from 12 patients with nasal allergy were measured by RIA method. The activities of arylsulfatase B in the nasal secretions and the sera were also estimated in the same specimens as ECP by measuring its hydrolytic activity using p-nitro cathecol sulfate as a substrate. The results obtained were as follows; 1) There was a significant correlation between ECP concentrations in the nasal secretions and the severities of clinical symptoms, especially the degree of nasal obstruction. ECP concentrations also significantly correlated to the score of eosinophilic leucocytes in the nasal smears. 2) The serum ECP concentrations significantly correlated to the number of eosinophilic leucocytes in the peripheral blood, and also showed slight tendency of correlation to the severity of clinical symptoms.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1886033 TI - [Transcutaneous intrafold injection result and its influencing factors]. AB - The result of transcutaneous intrafold injection and its influencing factors were studied for fifty five procedures in fifty two patients with unilateral recurrent nerve paralysis. Maximum phonation time, mean air flow rate and amplitude perturbation quotient of the voice were normalized or improved after the procedures more than 85%. In general assessment with functional and acoustic examinations, 76% of the procedures showed significant improvement. The paralysis after the thoracic surgery, right vocal fold paralysis and the paralysis complicated with sulcus vocalic tended to have insufficient improvement after injection. The most significant correlation to the result was shown in the degree of vocal fold augmentation immediately after injection. It was depend on the surgeon's technique and the patient's problems such as an anatomical abnormality of the larynx and an insufficient inhibition of the gag reflex. PMID- 1886034 TI - [Active posterior rhinomanometry by means of a fine nasal catheter for obtaining postnasal pressure]. AB - Recent years, active anterior rhinomanometry using a anesthetic face mask is probably more commonly employed than active posterior rhinomanometry because of occasional failure in obtaining the oropharyngeal pressure in the latter method. Thus, in attempt to overcome the disadvantage in active posterior rhinomanometry, we employed a fine nasal catheter (# 8F infant feeding nasal catheter) through the nasal cavity instead of a peroral mouth piece. Nasal resistances in a normal adult were measured by mask active posterior rhinomanometry with a mouth piece or a nasal catheter for obtaining postnasal pressure using Rhinorheograph MPR -2100 (manufactured by Nihon-Kohden Co., Ltd.). In adult, no significant differences of unilateral and bilateral nasal resistances between with the mouth piece and with the nasal catheter were found either on inspiration or expiration. It could be concluded in this fundamental study that active posterior rhinomanometry with the fine nasal catheter is useful and has no procedure problems. PMID- 1886035 TI - Examination of neurons in wild type and mutants of Caenorhabditis elegans using antibodies to horseradish peroxidase. AB - Antibodies to horseradish peroxidase (HRP) recognize 27 of 302 neurons and several non-neuronal cells in adult hermaphrodites of the soil nematode Caenorhabditis elegans and can be used to label these cells for cytological analysis in whole animals. The antibodies bind to the anterior members, but not to the posterior members of a set of mechanosensory neurons in wild type animals. Binding to one of the posterior mechanosensory neurons (PVM) occurs when this neuron migrates to an abnormal anterior position in mab-5 mutant animals, suggesting that expression of the epitope recognized by these antibodies is position dependent or that mab-5 mutations transform PVM into AVM intrinsically. The antibodies were used to characterize morphologies of two pairs of lumbar neurons (PHC and PVN) in uncoordinated mutants representing 95 unc genes. PHC and PVN morphologies were normal in most of the unc mutants examined, however, in mutants of 9 unc genes (unc-6, unc-13, unc-33, unc-44, unc-51, unc-61, unc-71, unc-73, and unc-98), misdirected PHC and/or PVN processes were observed at a high frequency. The morphologies of 2 other lumbar neurons, PHA and PHB, were determined previously in these mutants (Hedgecock et al., 1985). Mutations in most, but not all of these 9 unc genes affect the growth of the embryonic lumbar neurons PHA and PHB differently than they affect the growth of the postembryonic lumbar neurons PHC and PVN, indicating that these neurons require different, but overlapping sets of genes for different stages of normal growth and guidance. PMID- 1886036 TI - Remarks by the Commissioner. FDA. PMID- 1886037 TI - Carleton's Corner. Apples, oranges, and additive assurance. PMID- 1886038 TI - Photostabilization of riboflavin by incorporation into liposomes. AB - The influence of liposomes on the photostabilization of riboflavin in an aqueous formulation was studied under fluorescent light at various conditions. Liposomal composition, concentration, pH, and ionic strength were varied. The photostability of riboflavin was found to increase in the presence of neutral and negatively-charged liposomes but to decrease in association with positively charged liposomes. Furthermore, increasing the concentration of dimyristoyl phosphatidylcholine (DMPC) in the composition of the liposomes resulted in an enhancement in the photostability of riboflavin such that at 5.8mM DMPC concentration a 2.3 fold increase in photostability was observed compared to control buffer solution. The pH of the medium influenced the photostability of riboflavin. However, the ionic strength of solution appeared to demonstrate no significant effect. The photodegradation reactions appeared to follow first-order kinetics in the presence and absence of liposomes. PMID- 1886039 TI - Gowning training: the use of video recording together with microbial assessment. AB - Following classroom training on proper aseptic gowning technique, clean room operators were filmed while gowning according to standard procedure. Subsequently, the exterior surface of each operator's gown was monitored for microbial contamination. Operators reviewed their personal videotaping with the trainer. Through careful and critical self-observation, the operator's ability to follow the gowning procedure in addition to using good gowning technique was ascertained. Furthermore, the operator's gowning technique was compared with the results of the microbiological monitoring data. A correlation between microbial contamination of the gown surface and improper technique was demonstrated. This correlation enhanced the operator's awareness of the consequences of improper gowning technique. Use of video replay enabled the operator and trainer to identify improper or subtle flaws in technique detected through microbial monitoring but undetected during actual gowning. This training program served to further emphasize the importance of using proper aseptic gowning technique. Clean room operators are more involved in maintaining clean room integrity and their awareness of the potential for contaminating the area by inadequate technique has been enhanced. PMID- 1886040 TI - Facility requirements for biotech plants. PMID- 1886041 TI - Regulations, proposals, guidelines, advisory opinions, and letters of advice: what legal significance? PMID- 1886042 TI - FDA inspections in Canada. PMID- 1886043 TI - Solubilities of trimethoprim and sulfamethoxazole at various pH values and crystallization of trimethoprim from infusion fluids. AB - Solubilities of sulfamethoxazole (SMX) and trimethoprim (TMP) have been measured in the absence and presence of various concentrations of hydroxypropyl beta cyclodextrin (HPCD) in buffers over a range of pH values. The solubilities of TMP increased linearly in the presence of HPCD at pH values of 7.0, 7.5, 8.9, and 9.9 indicating the formation of 1 to 1 complexes, whose association values increase as pH does and as the ionization of TMP decreases. For SMX at pH 7.0, a 1:1 complex is formed, but at pH 7.5 HPCD has little effect on the solubility of the highly ionized SMX, presumably since only un-ionized molecules can form inclusion complexes with the HPCD. At pH 7.0 when solubilities of TMP and SMX are measured in the same system containing buffer and HPCD, a massive decrease in the solubility of TMP is found, while that of SMX decreases slightly. A slightly soluble complex of TMP/SMX may be formed. When TMP/SMX injection is diluted 1;10 with phosphate buffer (pH 7.8), an immediate massive precipitation which is mostly TMP is observed. The presence of 10% w/v HPCD in the buffer delays and modifies the precipitation of TMP and SMX but does not prevent it. Mixing the injection (1 to 10) with normal saline (pH 9.5) gives a steadily increasing precipitation of TMP with time, but no discernible change in the concentration of SMX. However, in normal saline containing 10% w/v HPCD there is no crystallization of either drug over a 5 day period. PMID- 1886044 TI - Good manufacturing practices and clinical supplies. AB - Quality characteristics must be assured through adherence to good manufacturing practices in the production, control, and testing of drug products intended for investigational as well as commercial use. A draft guideline on the preparation of investigational new drug products, soon to be available in final form, addresses questions that have been raised regarding acceptable practices and procedures to facilitate compliance with the CGMP regulations as applied to clinical supplies. Inspections of sterile clinical supplies production can be expected to include the areas most likely to influence product safety, quality, and uniformity in the same manner as would be expected regarding the manufacture of commercial batches. Some areas of particular significance in the manufacture of parenteral clinical supplies include validation of terminal sterilization, aseptic processing, and oxygen exclusion. The validation of the aseptic handling during lyophilization requires special attention. Other CGMP concerns include the provision of a quality control unit, avoiding packaging mixups, and being prepared for an amendment to the CGMP regulations regarding terminal sterilization. PMID- 1886045 TI - Solubilization of aluminum-containing adjuvants by constituents of interstitial fluid. AB - The solubilization of three commercially available aluminum-containing adjuvants by citrate anion was studied. Amorphous aluminum hydroxyphosphate and boehmite were both solubilized, however, amorphous aluminum hydroxyphosphate dissolved significantly faster than boehmite. The results suggest that citrate and other alpha-hydroxy carboxylate anions in the interstitial fluid are able to solubilize and thereby facilitate the excretion of aluminum from aluminum-containing adjuvants which are administered by intramuscular injection. The results also suggest that the release of antigen following administration may be significantly more rapid from an amorphous aluminum hydroxyphosphate-adjuvanted vaccine in comparison to a boehmite-adjuvanted vaccine. PMID- 1886046 TI - The use of surface tension measurements in the design of antibody-based product formulations. AB - Many proteins in aqueous solution are susceptible to interfacial denaturation and precipitation during mechanical agitation. With the large number of protein parenteral products currently in research or clinical testing, it is important not only to understand this denaturation process but also to develop effective methods for stabilizing the products. Surfactants, such as Polysorbate 80 or sodium dodecyl sulfate (SDS), are frequently used to stabilize parenteral products. While it is a commonly accepted technique, little has been published about the precipitation and stabilization processes in general. We describe the stabilization of antibody products in solution by preferential adsorption of a water-soluble, non-ionic surfactant at the air-liquid interface. Data are presented from antibody and immunotoxin solution shake studies and surface tension measurements to support the utility of surface tension measurements in formulation design. PMID- 1886047 TI - Alcohol use and attitudes: a comparison of college athletes and nonathletes. AB - The purpose of this study was to compare patterns of use and attitudes toward alcohol by college athletes and nonathletes. One hundred forty-six college students from colleges in the Jackson, Mississippi area were compared on athletic participation, sex, and race as these variables affected alcohol use and attitudes toward use. Data were collected by means of a questionnaire administered by the investigators. Chi squares and t-tests for differences between means were utilized to assess differences among subgroups on dependent variables. Analysis of data indicated that minimal differences existed in drinking behaviors of athletes and nonathletes. Athletic participation exerted a slight influence upon the drink of choice and patterns of drinking. Some significant racial and gender-related differences were found in drinking behaviors. The more negative attitudes of athletes toward alcohol consumption did not result in drinking behaviors distinct from nonathletes. PMID- 1886048 TI - Disease versus social-learning models of alcoholism in the prediction of alcohol problem recognition, help-seeking, and stigma. AB - Subjects (N = 254) were presented with either a disease or social-learning view of alcoholism and their subsequent attitudes were examined. Presentation of a disease view strengthened endorsement of that model, but attitudes toward alcoholics, treatment effectiveness, problem recognition, and help-seeking were not significantly different between the experimental conditions. Differences in attitudes between high and low disease and social-learning belief subjects were examined in 2 x 2 ANOVAs. Separate multiple regression analyses with alcohol problem recognition, help-seeking, and stigma as composite dependent variables and etiologic beliefs, drinking measures, family history of alcoholism, and responsibility for drinking problems as independent variables were performed. Results show that neither disease nor social-learning beliefs are particularly effective in predicting the dependent variables. PMID- 1886049 TI - Antecedents and correlates of alcohol, cocaine, and alcohol-cocaine abuse in early adulthood. AB - We used a fourfold substance abuse typology consisting of non-abusers, alcohol abusers, cocaine abusers, and joint alcohol and cocaine abusers with a nationally representative sample of young adults (aged 19-26 years) to investigate issues related to prevalence, antecedents, and correlates of substance abuse. The prevalence data indicate higher alcohol abuse among white males, but approximately equal proportions of cocaine abuse and joint alcohol and cocaine abuse across gender and ethnic/racial groups. A simplex-like ordering was found for the four abuse groups with regard to the degree of problem severity associated with most of the antecedents and correlates. Joint alcohol and cocaine abusers demonstrated the highest levels of previous thirty-day and lifetime drug use, high levels of delinquent activity, and the highest rates of unemployment and marital instability. Cocaine abusers demonstrated the second highest levels of problem severity, alcohol abusers the third highest levels, and non-abusers the lowest levels. An exception to the simplex-like pattern was found with respect to educational attainment and verbal intelligence. Joint alcohol and cocaine abusers reported the lowest high school dropout rate and scored the highest on a measure of verbal intelligence. We suggest that joint alcohol and cocaine abusers may be characterized as "non-strivers" or "underachievers," quite possibly as a consequence of substance abuse. PMID- 1886050 TI - Young adults' knowledge of the strength of different alcoholic beverages. AB - Providing information about the strength of different alcoholic beverages is a common component of alcohol abuse prevention programs. However, little is known about drinkers' knowledge of the strength of different alcoholic beverages. In the present study, 113 young adult drinkers responded to a questionnaire concerning the alcohol content of different types of malt beverages (beers, malt liquors), wines, fortified wines (port, sherry), and distilled spirits. The results indicated rates of correct responses well below 50 percent for each type of alcoholic beverage, with a substantial proportion of subjects either overestimating or underestimating alcohol content. Not a single subject reported correct alcohol content values for all four beverage types. There was a trend towards less accurate estimates of the alcohol content of strength were less accurate than those of men. The results are discussed in terms of prevention of alcohol abuse. PMID- 1886051 TI - Predictors of alcohol abuse behaviors of undergraduates. AB - A representative sample of 713 Mary Washington College undergraduates responded to questions about alcohol effects, their own alcohol use, and their beliefs about the risks associated with alcohol use for college students in general and for themselves in particular. Item correlations suggested four indexes: personal risk of abuse, personal risk of alcohol-related misfortune, alcohol consumption, and alcohol abuse. Knowledge did not predict reduced use or abuse patterns, nor did perceived risk of abuse for students in general. Abuse, consumption and personal risk of abuse were all positively intercorrelated. However, personal risk of alcohol-related misfortune was negatively correlated with all other indexes. These findings have important implications for programs to reduce alcohol abuse among young people. PMID- 1886052 TI - The stigmatization of smokers: an empirical investigation. AB - This study examines the social stigmatization of tobacco smokers, i.e., the extent to which smokers are seen as discredited persons. A representative sample of residents of a major Canadian city was interviewed. Clear evidence of an unfavorable stereotype of smokers was found. The ex-smoker enjoys a positive image, but one which is slightly less favorable than that of someone who has never smoked. A majority of non-smoking respondents preferred non-smokers in roles in which the role incumbents were likely to be in close proximity. Friendship networks and marital relationships tended to be segregated along lines of smoking behavior. Sociodemographic and attitudinal correlates of anti-smoker attitudes are explored. The implications of stigmatization for changing smokers' behavior are examined. PMID- 1886053 TI - Be a winner: Arkansas' approach to involving law enforcement officers in drug education. AB - This paper describes a project which is a joint venture of the Northwest Arkansas Police Institute and the Program in Health Sciences at the University of Arkansas. Funded by the U.S. Department of Education under the Drug Free Schools and Communities Act, the focus of the project has been the development of an innovative drug education program which brings uniformed law enforcement officers into the elementary school classroom. The officers lead an eight week instructional program at the fifth or sixth grade levels using our Be A Winner curriculum. PMID- 1886054 TI - Sources of drug information among adolescent students. AB - A sample of 1023 eighth and tenth grade students in small to medium-sized central Texas school districts was assessed to determine the amount of information they receive from ten sources about six categories of drugs. The amount of information males reported receiving about each drug category was significantly greater than what females reported, and the amount of information that eighth graders reported receiving about each drug category was significantly greater than what tenth graders reported. Television was the primary source of drug information for all categories of drugs except inhalants, for which friends and television were equally important sources. Parents and printed media (magazines or newspapers) were of secondary importance, followed by friends and teachers. Adolescents were less likely to receive drug-related information from experience, siblings, church, doctors, and police. The reliance on the mass media for drug information in smaller school districts is a pattern which has been previously observed in larger urban districts. This consistency suggests that mass media approaches to drug education are likely to be as effective in rural areas and smaller towns as they are among urban adolescents. Implications for television programming are discussed. PMID- 1886055 TI - The effects of compression upon conduction in myelinated axons of the isolated frog sciatic nerve. AB - 1. Action potential conduction along frog sciatic nerve fibres has been monitored during compression of a mid-portion of the nerve. 2. The effects of compressing a 24 mm length of nerve with a pressure of 250 mmHg applied pneumatically were investigated by recording unitary action potentials. A plot of time before conduction failure (survival time) against initial conduction velocity revealed that the faster myelinated axons tend to fail before the slower myelinated axons. A large degree of scatter was evident in the pooled data as well as in the data from individual experiments. 3. When the compression was made more severe by increasing the applied pressure to 750 mmHg, the order of block was reversed, i.e. the slower myelinated axons tended to block first. Similar scatter in the order of conduction block was observed. 4. The average survival time of units following application of compression was considerably different between these two series of experiments. When 750 mmHg pressure was applied, units survived for, on average, 10.9 min (n = 246). When 250 mmHg pressure was applied units survived for, on average, 50.4 min (n = 148). 5. The results are discussed in relation to the underlying causes of conduction failure as a result of compression and in relation to results from previous investigations. PMID- 1886056 TI - Pairing of pre- and postsynaptic activities in cerebellar Purkinje cells induces long-term changes in synaptic efficacy in vitro. AB - 1. An in vitro slice preparation of rat cerebellar cortex was used to analyse long-lasting modifications of synaptic transmission at parallel fibre (PF) Purkinje cell (PC) synapses. These use-dependent changes were induced by pairing PF-mediated EPSPs evoked at low frequency (1 Hz) with different levels of membrane polarization (or bioelectrical activities) of PCs for 15 min. 2. Experiments were performed on forty-eight PCs recorded intracellularly in a conventional perfused chamber, and in fifty other cells maintained in a static chamber either in the presence (n = 21) or in the absence (n = 29) of 400 nM phorbol 12,13-dibutyrate (PDBu). 3. In these three experimental conditions, PF mediated EPSPs were always measured on PCs maintained at a holding potential of 75 mV, and further hyperpolarized by constant hyperpolarizing pulses. This allowed us both to test the input resistance of PCs and to avoid their firing during PF-mediated EPSPs. 4. In all cells retained for the present study, latencies of PF-mediated EPSPs evoked at 0.2 Hz were stable during the pre pairing period, and the same was true for their amplitude and time course. 5. In the perfused chamber, pairing of PF-mediated EPSPs with the same hyperpolarization of PCs as that used for measurements of synaptic responses had no effect on these EPSPs in 30% of PCs. It induced long-term depression (LTD) and long-term potentiation (LTP) in 23 and 47% of the tested cells respectively (n = 17). 6. In the perfused chamber, pairing of PF-mediated EPSPs with moderate depolarization of PCs (n = 19) giving rise to a sustained firing of sodium spikes significantly favoured the appearance of LTP as compared to the previous pairing protocol. However, there were still 27 and 15% of cells which showed no modification and LTD respectively. 7. In contrast, pairing of PF-mediated EPSPs with calcium (Ca2+) spikes evoked by strong depolarization of PCs (n = 12) led to LTD of synaptic transmission in nearly half of the tested cells, whereas LTP was now observed in less than 20% of them. 8. In the static chamber and in the absence of PDBu, LTD of PF-mediated EPSPs was observed in most cells, whatever the pairing protocol with sodium or Ca2+ spikes. 9. This shift towards LTD was significantly reversed by PDBu in the pairing protocol using firing of sodium spikes, but not in the case of pairings with Ca2+ spikes.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1886057 TI - Suppression of steady membrane currents by acetylcholine in single smooth muscle cells of the guinea-pig gastric fundus. AB - 1. Single smooth muscle cells from the fundus region of the guinea-pig stomach, which showed contractile responses to acetylcholine (ACh) at concentrations greater than or equal to 10(-7) mol/l, were obtained by enzymatic digestion using highly purified collagenase and papain. They were studied by recording membrane currents under voltage clamp with the patch pipette technique in the whole-cell configuration at 25-28 degrees C. 2. By applying voltage jumps from negative holding levels (-70 to -60 mV) to more positive levels, we identified two major activating currents: an initial inward Ca2+ current (ICa) was followed, and partly overlapped, by an outward K+ current (IK). 3. Cholinergic effects on membrane currents were investigated in the range of negative membrane potentials by determining current-voltage relations in the absence of ACh and during its continuous presence in the bathing fluid. 4. ACh induced a decrease in the steady state conductance which was reversibly blocked by atropine. At physiological external K+ concentration [( K+]o = 6 mmol/l), the reversal potential (Erev) of the current suppressed by ACh (3 x 10(-6) mol/l) was about 20 mV more positive than the calculated K+ equilibrium potential (EK). 5. When [K+]o was increased, Erev was shifted positively; but at each [K+]o, Erev was more positive than EK. 6. Like ACh (10(-6) mol/l), tetraethylammonium (TEA, 1 mmol/l) also suppressed a current with a reversal potential that was, at physiological [K+]o, 20 mV more positive than EK. ACh (10(-5) mol/l) applied in the presence of 1 mmol/l TEA suppressed a pure K+ current (Erev = EK), which was also suppressed by 10 mmol/l TEA. 7. When K+ in the pipette and in the bathing solution was completely replaced by Na+, both ACh (10(-5) mol/l) and TEA (1 mmol/l) caused a reduction of the membrane conductance that appeared to be identical. TEA added to the bathing solution in the presence of ACh did not produce a significant additional conductance decrease. These results did not depend on whether Cl- was present as a charge carrier or not. 8. It is concluded that in fundus muscle of the guinea pig stomach a major mechanism underlying muscarinic activation is a decrease of a K+ conductance. In addition the results indicate a suppression of a small Na+ conductance which is made up by a population of channels that are also blocked by TEA. PMID- 1886058 TI - A fast, transient K+ current in neurohypophysial nerve terminals of the rat. AB - 1. Nerve terminals of the rat posterior pituitary were acutely dissociated and identified using a combination of morphological and immunohistochemical techniques. Macroscopic terminal membrane currents and voltages were studied using the whole-cell patch clamp technique. 2. In physiological solutions, depolarizing voltage clamp steps, from a holding potential (-80 mV) similar to the normal terminal resting potential, elicited a fast, inward followed by a fast, transient, outward current. 3. The threshold of activation for the outward current was -60 mV. The outward current quickly reached a peak and then decayed more slowly. The decay was fitted by two exponentials with time constants of 21 +/- 2.9 and 143 +/- 36 ms. These decay constants did not show a dependence on voltage. The time to peak of the outward current decreased and the amplitude increased with increasingly depolarized potential steps. 4. The outward current was blocked by the substitution of K+ with Cs+ and its reversal potential was consistent with a potassium current. 5. The transient outward current showed steady-state inactivation at more depolarized (than -80 mV) holding potentials with 50% inactivation occurring at -47.9 mV. The time course of recovery from inactivation was complex with full recovery taking greater than 16 s. 6. 4 Aminopyridine (4-AP) blocked the transient outward current in a dose-dependent manner (approximately IC50 = 3 mM), while charybdotoxin (4 micrograms/ml) and tetraethylammonium (100 mM) had no effect on the current amplitude. 7. Lowering external [Ca2+] had no effect on the fast, transient outward current nor did the calcium channel blocker Cd2+ (2 mM). 8. The neurohypophysial outward current reported here corresponds most closely to IA, and not to the delayed rectifier or Ca2(+)-activated K+ currents. Neurohypophysial IA, however, appears to be different from the outward currents found in the cell bodies in the hypothalamus which project their axons to the posterior pituitary. 9. Under current clamp, evoked action potential duration increased (122%) upon application of 5 mM-4-AP, indicating that IA is involved in neurohypophysial spike repolarization. 10. The existence of this current could help explain why maximal peptide release only occurs in response to bursts of electrical activity invading the nerve terminals. PMID- 1886059 TI - Correlation between the discharges of motor units recorded from the same and from different finger muscles in man. AB - 1. Cross-correlation analysis of the discharges of individual motor units recorded from various different finger muscles has been performed during weak, isometric, voluntary contractions in man. 2. The dominant feature in 88% of the cross-correlograms studied was a narrow, central peak, the area of which significantly exceeded that expected for independent processes (P less than 0.001). The highest bin counts in these central peaks were mostly within 5 ms of time zero in the histograms, and the base of these peaks extended between 5 and 31 ms (modal value = 13 ms with 90% of the values lying between 8 and 18 ms). The width and displacement of the central cross-correlogram peaks were similar irrespective of whether the contributory spike trains were recorded from motor units active in the same finger muscle or recorded from motor units in different, co-activated finger muscles. 3. The time course of the central peaks in this study was found to be consistent with the hypothesis that it is generated by the joint occurrence of EPSPs evoked in motoneurones by branches of common stem presynaptic fibres using the theoretical model developed by Kirkwood (Kirkwood & Sears, 1978). The model parameters providing the best fit with our experimental data imply that synaptic contacts on motoneurones made by these common inputs lie on average peripherally in the dendritic tree and generate small (less than 300 microV) EPSPs superimposed on a high level of background synaptic noise. 4. Minima (troughs) were found either side of the central peak in 27% of the cross correlograms studied, and their appearance was invariably associated with a large central peak. These secondary features could not be modelled with the same operator parameters that describe the central peaks. Their presence was particularly noticed in association with very regular discharges from the output motoneurones. 5. Smaller and broader secondary peaks symmetrically displaced 30 55 ms either side of the large, narrow central peak were observed in 7% of the cross-correlograms studied. We suggest that these secondary features which were found at lags shorter than the interspike interval of the contributory motor unit spike trains reflect the autocorrelation functions of the spike trains of common input fibres. On this basis the observed displacement of these secondary peaks from the primary feature in the cross-correlogram indicate firing rates for common input fibres in the range 18-33 impulses s-1. 6. In a small number of cases (1.4%) the cross-correlogram was flat and indistinguishable from the results of cross-correlating independent spike train data. PMID- 1886060 TI - Variation in the degree of synchronization exhibited by motor units lying in different finger muscles in man. AB - 1. Cross-correlation analysis was performed on the discharges of motor units recorded from the same or from different finger muscles during weak, voluntary isometric contractions in man. 2. In 88% of cases such cross-correlograms contained a narrow central peak indicating synchronization between the firing of the contributory motor units. Expressed in terms of the synchronization index, b (peak area/total number of reference plus response spikes) the amount of synchronization found in these different recordings ranged from b = 0.0057 to b = 0.1436 (n = 1230). The duration of the synchronization (measured across the base of the peak) ranged from 5 to 31 ms (mode = 13 ms). 3. For each pair of motor units examined the amount of synchronization between their firing varied from minute to minute of a long recording. In around half the cases studied this variation appeared to correspond to variation in the firing rates of the two motor units whereas in the other half of cases tested no relationship was found between the firing rates and the amount of synchronization. 4. Some motor unit pairings consistently showed more synchronization than other motor unit pairings within the same muscle. A frequency histogram of the synchrony measurements from all of the motor unit pairings tested in that muscle showed a unimodal and continuous distribution. 5. Some subjects consistently showed two or three times more motor unit synchronization than others in equivalent recordings. This rank order of motor unit synchronization in different subjects was found to be the same in all muscle pairings tested. 6. A similar distribution in the amount of motor unit synchronization found in different muscle pairings was found in all subjects tested. In the first place the firing of motor units which act on widely separated fingers was less synchronized than the firing of motor units acting on adjacent fingers. Secondly, motor units acting on the lateral fingers (thumb, index) showed less synchronization in their discharges than motor units acting on medial fingers (ring, little). Finally the firing of motor units in the finger flexor muscles were less synchronized than the firing of motor units in either the finger abductor or the finger extensor muscles. 7. The synchronization of motor unit activity in different muscles indicates the presence of a widespread projection pattern for the branches of some last-order input fibres to finger muscle motoneurones.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1886062 TI - Characteristics of sympathetic preganglionic neurones in the lumbar spinal cord of the cat. AB - 1. In anaesthetized cats extracellular recordings have been made from antidromically identified sympathetic preganglionic neurones, located in the 2nd and 3rd lumbar segments, with axons projecting into the left lumbar sympathetic chain beyond the L4 ganglion. Sympathetic preganglionic neurones have been characterized with respect to: axonal conduction velocities, firing patterns in relation to ECG and phrenic nerve activity, responses to noxious stimuli applied to the ipsilateral hindlimb and ionophoretically applied 5-HT. 2. Two hundred and ninety-seven sympathetic preganglionic neurones were studied. Their axonal conduction velocities (0.5-13.9 m/s) were in the B and C fibre range. Sixty-eight had on-going activity and the remainder were quiescent. Of the 229 quiescent sympathetic preganglionic neurons, 111 were activated by the ionophoretic application of glutamate. 3. Of the 100 sympathetic preganglionic neurones analysed for an ECG-related pattern of discharge, forty-nine had no, and fifty one had an ECG-related pattern of discharge. Both sympathetic preganglionic neurones with on-going activity and glutamate activated cells exhibited ECG related patterns of discharge. 4. Only six of fifty sympathetic preganglionic neurones had a respiratory-related activity pattern. Three had maximal discharge during expiration and three during inspiration. 5. Forty-one sympathetic preganglionic neurones were examined for their response to noxious stimulation of the ipsilateral hindlimb. Ten had their activity decreased (seven glutamate activated, three with on-going activity), seven had their activity increased (four glutamate-activated and three with on-going activity) and twenty-four were unaffected. These results demonstrate that both sympathetic preganglionic neurones with on-going activity and glutamate-activated neurones can be influenced by noxious input. Ten sympathetic preganglionic neurones had properties consistent with them having a skin vasoconstrictor function and three with muscle vasoconstrictor function. 6. Ionophoretic application of 5-HT in the vicinity of fifty-one sympathetic preganglionic neurones caused increases in the discharge of 53%, decreases in the firing of 12% and did not affect the discharge of 35%. 7. Sympathetic preganglionic neurones which had excitatory responses to 5 HT showed only decreased discharge or no response to noxious stimulation of the ipsilateral hindlimb. Conversely, sympathetic preganglionic neurones which had discharge decreased by 5-HT had primarily excitatory responses to noxious inputs. 8. It is concluded that lumbar sympathetic preganglionic neurones consist of a heterogeneous population with respect to their physiological properties and their responses to ionophoretically applied 5-HT: both may be related to function. PMID- 1886061 TI - Central nervous pathways underlying synchronization of human motor unit firing studied during voluntary contractions. AB - 1. Motor unit firing has been studied during weak voluntary isometric contractions with pairs of needle electrodes in normal human subjects. 2. Pre- and post-stimulus time histograms of the firing time of firing of one event unit before and after the time of firing of another reference (stimulus) unit showed a clear central peak, indicative of synchronization. 3. Synchronization was seen in all the muscles studied. The mean strength of synchronization, expressed as the number of concomitant discharges of the two units as a proportion of the number of stimulus unit discharges, was 0.095 extra event unit spikes/reference unit spike (range 0.042-0.28) for first dorsal interosseous muscle, 0.016 extra event unit spikes per reference unit spike (range 0-0.043) for medial gastrocnemius and 0.056 extra event unit spikes per reference unit spike range 0.016-0.079) for tibialis anterior. 4. The mean duration of synchronization was 11.3 ms (range 5.0 21.0 ms) for first dorsal interosseous, 10.3 ms (range 3.5-21.7 ms) for medial gastrocnemious and 13.5 ms (range 3.0-25.0) for tibialis anterior. 5. Seven patients with radiographically and clinically identified central strokes were studied while they made weak voluntary isometric contractions. The duration of synchronization was significantly prolonged compared to that found in normal subjects. In these stroke patients the mean duration of synchronization on the affected side was longer than that seen in the normal subjects, and in first dorsal interosseous muscle was 35.4 ms (range 12.0-65.0 ms), in medial gastrocnemius was 21.3 ms (range 4.0-43.0 ms) and in tibialis anterior was 28.8 ms (range 14.0-49.0 ms). 6. The mean strength of synchronization of motor unit discharge was found to be greater in the stroke patients than that seen in the normal subjects for first dorsal interosseous muscle (0.161 extra event unit spikes per reference unit spike, range 0.017-0.391) and for medial gastrocnemius (0.030 extra event unit spikes per reference unit spike) but only significantly so when pooled data was compared. There was no difference in the strength of motor unit synchronization in tibialis anterior between stroke patients and normal subjects. 7. Broad duration synchronization among first dorsal interosseous motor units was also found in a patient with a rostral cervical spine lesion (total duration range 43-46 ms; n = 2), but not in a patient with a caudal (thoracic) spinal lesion.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1886063 TI - Task-dependent changes in the responses to low-threshold cutaneous afferent volleys in the human lower limb. AB - 1. In seven human subjects who were standing without support the sural nerves were stimulated electrically using trains of non-painful stimuli (five pulses at 300 Hz), designed to activate afferents from cutaneous mechanoreceptors. The reflex effects of the stimulus train on different muscles of the ipsilateral and contralateral legs were sought in post-stimulus averages of rectified EMG. Changes in the pattern of reflex influence were investigated when the subjects maintained different postures. 2. Clear reflex responses were seen in ipsilateral tibialis anterior, soleus, biceps femoris and vastus lateralis, but only when the muscles were actively contracting. In each muscle, inhibition was the dominant reflex response within the first 100 ms. In four of the seven subjects, reflex changes were detectable in the contralateral tibialis anterior and soleus, the peak-to-peak modulation within the first 200 ms being 25-50% of that for the homologous ipsilateral muscle. 3. When subjects attempted to stand on a tilted platform, an unstable platform or on one leg with the other flexed, different combinations of muscles were active, involving both flexors and extensors or predominantly flexors or predominantly extensors. In each posture the reflex effects were demonstrable only in the active muscles. 4. With ipsilateral tibialis anterior, there were task-dependent changes in the short-latency components of the EMG response, approximately 60 ms and 80 ms after the stimulus. When seated performing voluntary contractions these components were difficult to define, and when standing on a platform tilted toe-up they were small. When the ipsilateral leg was flexed or when standing on an unstable base, these early components were more prominent in each subject. With contralateral tibialis anterior, the dominant reflex pattern was inhibition when seated and contracting voluntarily, and facilitation during bipedal stance tilted toe-up. These changes in reflex pattern could not be explained by different levels of background contraction. 5. It is concluded that cutaneous mechanoreceptors of the foot have widespread reflex actions on muscles throughout both limbs, particularly the ipsilateral limb, and that the reflex pattern in different muscles and within a single muscle may change dependent on the task that the subject is undertaking. These task-dependent changes indicate plasticity in the expression of cutaneous reflex activity, affecting both short-latency spinal as well as long-latency pathways. PMID- 1886065 TI - A physiological study of the prenatal development of cutaneous sensory inputs to dorsal horn cells in the rat. AB - 1. The response of fetal dorsal horn cells to natural and electrical stimulation of the skin of the hindpaw was recorded in vivo from the lumbar spinal cord of anaesthetized rat fetuses still in contact with their mother via the maternal circulation. 2. Responses to electrical stimulation were obtained from embryonic day 17 (E17) but spikes were not evoked by natural skin stimulation until embryonic day 19 (E19). 3. At E19 responses were evoked by pressure or pinching the skin, but responses to low intensity brush and touch were not clear until E20. 4. Receptive fields were small and response amplitudes and frequencies initially very low. However, by E20 bursts of up to fifty spikes were recorded to a single pinch and some cells displayed responses that outlasted the stimulus by 10-15 s. 5. The development of dorsal horn cutaneous evoked spike activity and consequently the ability to transmit cutaneous sensory information to the brain therefore occurs some 2 days after the development of peripheral afferent receptive fields. It is concluded that this represents the maturation time for central synaptic connections. PMID- 1886066 TI - Inhibition of atrial receptor-induced renal responses by stimulation of carotid baroreceptors in anaesthetized dogs. AB - 1. Dogs were anaesthetized with chloralose and artificially ventilated. The receptors at three pulmonary vein-atrial junctions and in the left atrial appendage were stimulated by distension of small balloons. The carotid sinuses were vascularly isolated and perfused with arterial blood. A volume reservoir was connected to the aorta via the common carotid and femoral arteries to keep the mean aortic pressure constant (78.8 +/- 2.9 mmHg at low and 87.1 +/- 4.3 mmHg at high carotid sinus pressure, CSP). Propranolol and atropine were infused (i.v.) at 17 and 13 micrograms kg-1 min-1 respectively in order to block beta-adrenergic and cholinergic receptor activities. The renal blood flow was measured by an electromagnetic flow meter (wrap-round probe), glomerular filtration rate by creatinine clearance, urinary sodium excretion by flame photometry and osmolar excretion by osmometry. 2. In twelve tests in eight dogs, stimulation of the left atrial receptors for 13 min, at a mean CSP of 68.6 +/- 2.3 mmHg, resulted in significant increases in renal blood flow from 216 +/- 20.0 to 230 +/- 22.1 ml min-1 (100 g renal mass)-1 (P less than 0.005), glomerular filtration rate from 33.9 +/- 3.2 to 42.1 +/- 4.1 ml min-1 100 g-1 (P less than 0.005), filtration fraction from 0.23 +/- 0.02 to 0.26 +/- 0.02 (P less than 0.005), urine flow rate from 0.21 +/- 0.03 to 0.26 +/- 0.03 ml min-1 100 g-1 (P less than 0.001), sodium excretion from 12.9 +/- 4.0 to 16.4 +/- 4.8 mumol min-1 100 g-1 (P less than 0.01), osmolar excretion from 196 +/- 27.8 to 246 +/- 32.9 muosmol min-1 100 g-1 (P less than 0.005), whilst free water clearance decreased from -0.39 +/- 0.07 to -0.50 +/- 0.09 ml min-1 100 g-1 (P less than 0.005). However, the fractional excretion of sodium did not change. 3. In nine tests in seven dogs, stimulation of the left atrial receptors at a constantly high CSP (161 +/- 11.3 mmHg) did not produce significant change in any of the renal variables. 4. The results show that high level excitation of carotid baroreceptors can completely inhibit the reflex renal haemodynamic and functional responses to atrial receptor stimulation. PMID- 1886064 TI - The effect of acidosis on the interval-force relation and mechanical restitution in ferret papillary muscle. AB - 1. The effect of a respiratory acidosis on the interval-force relation and on mechanical restitution was investigated in ferret papillary muscles. 2. Acidosis (pH 6.85) decreased developed force over a range of stimulation frequencies (1.0.06 Hz); the percentage decrease was greatest at the lowest stimulation frequencies. Qualitatively similar effects of acidosis on developed force were observed in the presence of the sarcoplasmic reticulum (SR) inhibitor ryanodine. 3. Mechanical restitution curves were constructed by interpolating extra-systoles at different test intervals following a train of steady-state beats. Mechanical restitution in ferret papillary muscle was triphasic: an initial, rapid, exponential increase in force with test intervals to 2 s, a further increase with test intervals between 60 and 90 s and then a slow decline, with a plateau at about 30 min (0.33 Hz, 30 degrees C). 4. Acidosis slowed the initial phase of mechanical restitution. The degree of slowing depended on the steady-state stimulation frequency, being greatest at low frequencies. 5. Inhibition of the SR abolished the initial phase of mechanical restitution, suggesting that this phase depends on Ca2+ release from the SR. 6. The strength of the first contraction after the extra-systole varied inversely with the size of the extra-systole under all conditions studied. 7. It is concluded that acidosis may inhibit the SR by altering the time required for Ca2+ recycling between contractions. This effect may alter Ca2+ release from the SR during acidosis, and may underlie the mechanical alternans (the alternation of small and large contractions) that can occur during acidosis. PMID- 1886067 TI - The influence of short-term adaptation of human rods and cones on cone-mediated grating visibility. AB - 1. The influences of short-term visual adaptation of either rods or cones upon cone-mediated grating visibility were compared with their influences upon detection threshold in both the fovea and parafoveal retina. Short-term visual adaptation was induced by 20 deg diameter adapting fields (AFs) generally of 500 ms duration. The AF was either -0.5 log td in illuminance and too dim to influence cones, or 2.5 log td and bright enough to stimulate cones as well as rods. 2. In control experiments, we replicated previous results of Crawford (1947), Baker (1963), and other investigators and determined the influence of these AFs upon the detection threshold of a homogeneous test flash (TF) of 54 min of arc diameter and 10 ms duration. If the AF was 2.5 log td in illuminance and stimuli were presented foveally, TF threshold began to rise several hundred milliseconds before AF onset, was maximal when AF and TF were simultaneous in onset but was less elevated during the remaining presentation of the AF. TF threshold decreased to control value within several seconds after AF offset. These data represent a cone adaptation function since action spectra for both the test and adapting flashes adhere to the spectral sensitivity of the CIE standard luminous efficiency function V lambda. 3. If the AF was -0.5 log td in illuminance and if stimuli were presented parafoveally, the time course of TF detection threshold changes were similar to those described in paragraph 2 above. But these data represent a rod adaptation function since action spectra for both the test and adapting flashes adhered to the spectral sensitivity of the CIE standard luminous efficiency function V' lambda. In the fovea, the -0.5 log td AF had no influence upon the detection threshold of the TF suggesting complete rod cone independence. 4. The influence of short-term adaptation upon spatial visibility was studied using a vertically oriented, 18 cycle/deg grating which was also 54 min of arc in diameter and 10 ms in duration. We determined the illuminance just necessary to see the bars of the grating (i.e. threshold grating illuminance or TGI) at various time intervals in respect to the onset of an AF. 5. Rod-stimulating (-0.5 log td) AFs, whether 0.5 or 2 s in duration, only influenced TGI after AF onset. TGI gradually decreased (i.e. an increase in sensitivity) during the first 250 ms of AF presentation and then remained stable until AF offset.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1886069 TI - Effect of somatic nerve stimulation on the kidney in intact, vagotomized and carotid sinus-denervated rats. AB - 1. The influence of cardiopulmonary and arterial baroreceptors on the renal nerve dependent functional responses of the kidney to electrical stimulation of somatic afferent nerves was studied in pentobarbitone-anaesthetized rats. 2. Electrical stimulation of the left brachial nerve plexus at 3 Hz, 0.2 ms and 15 V in the intact animals increased blood pressure by 22%, and while renal perfusion pressure was maintained at pre-stimulus levels, renal blood flow and glomerular filtration rate decreased by 14 and 22% respectively. At the same time urine flow rate and absolute and fractional sodium excretion decreased by 36, 42 and 27% respectively. In animals subjected to acute renal nerve section these renal functional responses could not be elicited. 3. Following bilateral vagotomy the systemic and renal haemodynamic responses to brachial nerve stimulation were similar to the intact group. However, urine flow rate and absolute and fractional sodium excretions decreased by 50, 59 and 47% respectively, responses which were significantly greater than in the intact group. 4. In a group of rats in which the carotid sinus nerves had been sectioned, stimulation of the brachial plexus caused reductions of renal blood flow and glomerular filtration rate of the same magnitude as in the intact group; however, urine flow rate and absolute and fractional sodium excretion fell by 51, 60 and 48%, respectively, which were significantly larger than in the intact group. 5. These results demonstrate that the afferent nerve information arising from muscle joints and skin and carried via the brachial plexus caused reflex renal nerve-dependent reductions in renal haemodynamics and an antidiuresis and antinatriuresis. The cardiopulmonary and carotid sinus baroreceptors exert a tonic inhibitory action on these reflex renal responses insofar as they appeared to attenuate the antidiuretic and antinatriuretic responses to somatic afferent nerve stimulation. PMID- 1886068 TI - Mean circulatory filling pressure during splanchnic nerve stimulation and whole body hypoxia in the anaesthetized cat. AB - 1. Mean circulatory filling pressure (MCFP) was measured in cats under chloralose anaesthesia by obstruction of blood flow in the pulmonary artery. Pressures in the aorta, hepatic portal vein and right atrium were recorded, and MCFP was estimated from the value at which all three pressures became equal when blood was pumped from aorta to vena cava during circulatory arrest. Simultaneous equality was not attained at MCFP values below 5 mmHg. 2. In cats ventilated by positive pressure after administration of gallamine, MCFP was 9.7 +/- 0.3 mmHg (n = 14). The values of MCFP measured in six cats before and after administration of gallamine did not differ significantly. Change of blood volume altered MCFP linearly over the range 5-21 mmHg. Noradrenaline (7.5 micrograms kg-1 min-1) increased MCFP from 9.3 +/- 0.9 to 16.5 +/- 0.6 mmHg (n = 4), and phentolamine (2 mg kg-1) reduced it to 5.6 +/- 0.3 mmHg (n = 5). 3. Changes in MCFP were evoked at different circulating blood volumes by stimulation of the splanchnic sympathetic nerves and by whole-body hypoxia. Ablation of all splanchnic nerves reduced MCFP from 9.4 +/- 0.5 to 7.1 +/- 0.3 mmHg (n = 5) and stimulation of their distal ends at 10 Hz increased it by 4.1 +/- 0.4 mmHg (n = 4); similar increments were obtained at different blood volumes and initial values of MCFP. 4. Hypoxia increased MCFP by 0.23 mmHg per 1 mmHg fall in arterial oxygen tension below Pa,O2 56 mmHg (r = -0.86; n = 24). Similar increments were obtained at different blood volumes and initial values of MCFP. Ablation of all splanchnic nerves reduced the increments by 60%, and administration of phentolamine abolished them. PMID- 1886070 TI - Salivary secretion and grooming behaviour during heat exposure in freely moving rats. AB - 1. At neutral (24 degrees C) and at hot (40 degrees C) ambient temperatures (Ta) salivary secretion from the submandibular gland of freely moving rats was recorded, together with simultaneous observation of saliva-spreading behaviour (grooming). 2. At a Ta of 24 degrees C, basal salivary flow was less than 2 microliters/min. When rats were first placed in the experimental chamber, brief grooming bouts often occurred. Transient secretion at more than 10 microliters/min was associated with this grooming, and the rate of salivary flow was positively correlated with the duration of grooming activity. 3. At a Ta of 40 degrees C, grooming appeared frequently and salivary secretion at more than 20 microliters/min continued even between grooming bouts. Threshold rectal temperatures (Tre) for thermally induced grooming (38.2 +/- 0.2 degrees C) and for salivary secretion (38.2 +/- 0.1 degrees C) were similar, and for eleven of sixteen rats the two thresholds coincided. 4. At the threshold Tre both the rate of salivary secretion and the duration of grooming increased in a stepwise fashion. Above the threshold, there was no correlation between the duration of grooming and the rate of salivary flow. 5. Thermally induced salivary secretion and grooming behaviour appear to be controlled by independent mechanisms. PMID- 1886071 TI - Depolarization-induced influx of sodium in response to phenylephrine in rat atrial heart muscle. AB - 1. The effects of alpha 1-adrenoceptor stimulation on transmembrane potential, currents and ion fluxes were investigated in multicellular preparations and/or single cells obtained from the left atrium of rat hearts. 2. In multicellular preparations, phenylephrine caused a concentration-dependent positive inotropic effect, an increase in action potential duration, and a decrease in resting potential; the effects were antagonized by phentolamine. 3. In the presence of phenylephrine (100 mumol/1), two levels of resting potential were observed when the preparations were, alternately, electrically stimulated or kept at rest (-74 +/- 1 mV during activity and -62 +/- 4 mV at rest; mean +/- S.E.M.; n = 9). 4. In resting preparations, the depolarization in response to phenylephrine was eliminated in low-Na+ solution (12 mmol/l) and antagonized by tetrodotoxin (10 mumol/l). 5. The phenylephrine-induced depolarization was also seen in nominally Ca(2+)-free solution and in the presence of (-)-devapamil (1 mumol/l). 6. The alkylating agent N-ethyl-maleimide (30 mumol/l) abolished the depolarizing effect of phenylephrine. 7. Phorbol 12,13-dibutyrate (10 mumol/l) also abolished the depolarizing effect of phenylephrine. 8. Phenylephrine caused a significant increase of 22Na+ uptake in resting preparations and of 45Ca2+ uptake in beating preparations. 9. The depolarizing effect of phenylephrine was also observed in single atrial myocytes. Steady-state membrane currents in response to 500 ms depolarizing and hyperpolarizing voltage clamp steps were decreased. The cross over of I-V curves under control and test conditions was at about -70 mV. The effects of phenylephrine were antagonized in the presence of phentolamine. 10. After suppression of potassium currents by substitution of CsCl for internal and external KCl ([KCl]o), phenylephrine had no effect on membrane currents. 11. In conclusion, we presume the following sequence of events in response to phenylephrine in rat atrial heart muscle. First, the stimulation of alpha 1 adrenoceptors decreases the K+ conductance thereby producing a depolarization in the presence of an inward current. Second, the change of the membrane potential in the depolarizing direction induces a TTX-sensitive Na+ window current which further propels the depolarization. Third, the increase in Na+ influx may increase Ca2+ influx by activating the Na(+)-Ca2+ exchange in mechanism. The greater influx of Ca2+ may contribute to the positive inotropic effect in response to phenylephrine. PMID- 1886072 TI - Cross-bridge kinetics in the presence of MgADP investigated by photolysis of caged ATP in rabbit psoas muscle fibres. AB - 1. The interaction between MgADP and rigor cross-bridges in glycerol-extracted single fibres from rabbit psoas muscle has been investigated using laser pulse photolysis of caged ATP (P3-1(2-nitrophenyl)ethyladenosine 5'-triphosphate) in the presence of MgADP and following small length changes applied to the rigor fibre. 2. Addition of 465 microM-MgADP to a rigor fibre caused rigor tension to decrease by 15.3 +/- 0.7% (S.E.M., n = 24 trials in thirteen fibres). The half saturation value for this tension reduction was 18 +/- 4 microM (n = 23, thirteen fibres). 3. Relaxation from rigor by photolysis of caged ATP in the absence of Ca2+ was markedly slowed by inclusion of 20 microM-2 mM-MgADP in the photolysis medium. 4. Four phases of tension relaxation occurred with MgADP in the medium: at, a quick partial relaxation (in pre-stretch fibres); bt, a slowing of relaxation or a rise in tension for 50-100 ms; ct, a sudden acceleration of relaxation; and dt, a final, nearly exponential relaxation. 5. Experiments at varied MgATP and MgADP concentrations suggested that phase at is due to MgATP binding to nucleotide-free cross-bridges. 6. Phase bt was abbreviated by including 1-20 mM-orthophosphate (Pi) in the photolysis medium, or by applying quick stretches before photolysis or during phase bt. These results suggest that phases bt and ct are complex processes involving ADP dissociation, cross-bridge reattachment and co-operative detachment involving filament sliding and the Ca(2+)-regulatory system. 7. Stretching relaxed muscle fibres to 3.2-3.4 microns striation spacing followed by ATP removal and release of the rigor fibre until tension fell below the relaxed level allowed investigation of the strain dependence of relaxation in the regions of negative cross-bridge strain. In the presence of 50 microM-2 mM-MgADP and either 10 mM-Pi or 20 mM-2,3-butanedione monoxime, relaxation following photolysis of caged ATP was 6- to 8-fold faster for negatively strained cross-bridges than for positively strained ones. This marked strain dependence of cross-bridge detachment is predicted from the model of A. F. Huxley (1957). 8. In the presence of Ca2+, activation of contraction following photolysis of caged ATP was slowed by inclusion of 20-500 microM-MgADP in the medium. An initial decrease in tension related to cross-bridge detachment by MgATP was markedly suppressed in the presence of MgADP. 9. Ten millimolar Pi partly suppressed active tension generation in the presence of MgADP.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1886073 TI - Responses of slowly and rapidly adapting receptors in the airways of rabbits to changes in the Starling forces. AB - 1. The responses of the rapidly adapting receptors (RARs) and the slowly adapting receptors (SARs) of the airways to changes in the Starling forces regulating fluid exchange in the pulmonary extravascular space were investigated in anaesthetized rabbits. The hydrostatic pressure in the pulmonary microvasculature was raised by partial obstruction of the mitral valve (mean left atrial pressure increased by approximately 5 and 10 mmHg above the control values) and the concentration of plasma proteins was reduced by plasmapheresis (the total plasma protein concentration reduced by 18%). 2. There was a significant correlation between the action potentials generated by RARs and mean left atrial pressure (n = 12). A similar response was not observed in SARs (n = 12). 3. After plasmapheresis, there was an increase in the resting activity of the RARs (n = 5). In addition, the stimulus-response curve relating mean left atrial pressure and RAR activity was significantly shifted to the left compared to the one elicited before plasmapheresis. Plasmapheresis failed to influence the activity of SARs (n = 5). 4. Obstruction of the pulmonary lymph flow by raising the afterload in the right external jugular vein caused a significant increase in the activity of RARs (n = 6). This response was also maintained during the entire period of lymphatic obstruction. 5. The results show that manipulation of the Starling forces within the lung influences the RAR activity profoundly. It is suggested that the stimulus for the RARs may be a function of the fluid fluxes in the pulmonary extravascular space. PMID- 1886074 TI - Differential sensitivity in the sites of fever production by prostaglandin E1 within the hypothalamus of the rat. AB - 1. The febrile sensitivity of male Sprague-Dawley rats to microinjections of prostaglandin E1 (PGE) was investigated at three different locations in the rostromedial hypothalamic region. These were the preoptic anterior hypothalamic area (PO-AH), the organum vasculosum laminae terminalis (OVLT) and the rostral third ventricle (3V). 2. Stainless-steel cannula guide tubes were implanted in the OVLT region of one group of animals, within the PO-AH area of a second group and into the third ventricle of a third group of rats. After their recovery, the febrile response of each group was tested to a variety of doses of PGE, each administered in a volume of 1 microliter sterile 0.9% saline, via a sterile cannula inserted into the implanted guide tubes. Metabolic, vasomotor and rectal temperature changes were monitored continuously for the duration of the fevers. 3. Surprisingly, not only did the introduction of PGE into the OVLT region produce fevers, but the sensitivity of this region to PGE in the production of fever greatly exceeded that of the PO-AH area and the third ventricle. Fevers produced by microinjection of PGE into the PO-AH and 3V were identical. 4. Doses of PGE as low as 0.5 ng injected into the OVLT produced fevers of 0.5 degrees C. The fever dose threshold for the OVLT region was one-fifth those of the PO-AH area and the 3V, and the slope of the OVLT dose-response curve was twice those of the PO-AH and the 3V dose-response curves. 5. This study demonstrates that there is an anatomically distinct, regional sensitivity in the febrile responsiveness to PGE within the hypothalamus. These results are interpreted as evidence that the site of action of PGE in the production of fever is located within or immediately adjacent to the OVLT region, rather than within the medial PO-AH neuropil as has been believed previously. PMID- 1886075 TI - Repetition priming with aspect and agreement morphology in American Sign Language. AB - Two experiments are reported which investigate the organization and recognition of morphologically complex forms in American Sign Language (ASL) using a repetition priming technique. Three major questions were addressed: (1) Is morphological priming a modality-independent process? (2) Do the different properties of agreement and aspect morphology in ASL affect priming strength? (3) Does early language experience influence the pattern of morphological priming? Prime-target pairs (separated by 26-32 items) were presented to deaf subjects for lexical decision. Primes were inflected for either agreement (dual, reciprocal, multiple) or aspect (habitual, continual); targets were always the base form of the verb. Results of Experiment 1 indicated that subjects exposed to ASL in late childhood were not as sensitive to morphological complexity as native signers, but this result was not replicated in Experiment 2. Both experiments showed stronger facilitation with aspect morphology compared to agreement morphology. Repetition priming was not observed for nonsigns. The scope and structure of the morphological rules for ASL aspect and agreement are argued to explain the different patterns of morphological priming. PMID- 1886076 TI - Complement C5a receptor assay for high throughput screening. AB - The complement C5a receptor on U937 cells, a human histiocytic lymphoma cell line, stimulated with dibutyryl-cAMP have been stabilized for at least 3 months at a dilute, ready to use concentration. [125I]-Bolton Hunter labeled C5a, (recombinant, human) has been prepared by reverse phase HPLC to 2200 Ci/mmol. Using a filtration binding assay the Kd from receptor saturation analysis is 10 40 pM and there are 50,000-100,000 receptor sites per cell. These reagents have permitted the development of a reliable, reproducible and convenient drug screening assay, in kit format, for compounds acting at the C5a receptor. PMID- 1886077 TI - The binding of [3H]AF-DX 384 to rat ileal smooth muscle muscarinic receptors. AB - The tritiated cardioselective muscarinic antagonist AF-DX 384 (5,11-dihydro-11-[2 (-[8-dipropylamino)methyl]-1-piperidinyl]-ethyl] amino]-carbonyl]-6H-pyrido [2,3 b] [1,4]benzodiazepin-6-one) was used to label muscarinic receptors in the rat ileum. Saturation binding to membrane suspensions revealed a high affinity binding site with a Kd of 9.2 nM. The maximal number of binding sites labeled in this tissue (Bmax) is 237 fmol/mg protein. The association and dissociation kinetics were well represented by single exponential reactions, and the dissociation constant obtained from the ratio of rate constants was in agreement with that derived from saturation experiments. Specific binding was inhibited by muscarinic antagonists with a rank order of potencies of atropine (pKi: 8.80) greater than 4-DAMP (pKi: 8.23) = AF-DX 384 (pKi: 8.20) greater than AF-DX 116 (pKi: 7.09) = hexahydro-sila-difenidol (pKi: 6.97) greater than pirenzepine (pKi: 6.49) and is consistent with the interaction of [3H]AF-DX 384 with muscarinic receptors of the M2 subtype. It can be concluded that [3H]AF-DX 384 can be used to selectively label M2 muscarinic receptors in heterogeneous receptor populations. PMID- 1886078 TI - Endogenous dopamine (DA) modulates [3H]spiperone binding in vivo in rat brain. AB - [3H]spiperone (SPI) binding in vivo, biochemical parameters and behavior were measured after modulating DA levels by various drug treatments. DA releasers and uptake inhibitors increased SPI binding in rat striatum. In other brain areas, the effects were variable, but only the pituitary remained unaffected. Surprisingly, nomifensine decreased SPI binding in frontal cortex. The effects of these drugs were monitored by measuring DA, serotonin (5-HT) and their metabolites in the same rats. The increased SPI binding in striatum was parallel to the locomotor stimulation with the following rank order: amfonelic acid greater than nomifensine greater than D-amphetamine greater than or equal to methylphenidate greater than amineptine greater than bupropion. Decreasing DA levels with reserpine or alpha-methyl-para-tyrosine reduced SPI binding by 45% in striatum only when both drugs were combined. In contrast, reserpine enhanced SPI binding in pituitary. Thus, the amount of releasable DA seems to modulate SPI binding characteristics. It is suggested that in vivo, DA receptors are submitted to dynamic regulation in response to changes in intrasynaptic concentrations of DA. PMID- 1886079 TI - Molecular design of novel ligands for 5-HT1A receptors. AB - Serotonin (5-HT) is a potent bioactive substance known to function through a number of different receptor types and subtypes. In our attempt to develop new agents that would interact selectively at certain 5-HT receptors, especially the 5-HT1A subtype, 8-hydroxy-2-di-n-propylamino tetralin (8-OH-DPAT) served as a template for the design of novel agents sharing aspects of the pharmacophore of 8 OH-DPAT and 5-HT. 5-HT contains no center of asymmetry, and 8-OH-DPAT shows only very modest stereospecificity for 5-HT1A receptors. To develop agents having enhanced potency and selectivity for the 5-HT1A site, several ring systems offering enhanced conformational rigidity which approximate the oxygen to nitrogen interatomic distances of 8-OH-DPAT and (to a lesser extent) 5-HT were synthesized. Exemplary ring systems include the 8-alkoxy-hexahydroindeno[1,2 c]pyrrole, 5-alkoxy-hexahydro-1H-indeno-[2,1-c]pyridine, and 9-alkoxy-hexahydro 1H-benz[e]isoindole systems. These conformationally restricted molecules demonstrated moderate stereospecificity in their interaction with the 5-HT1A binding site, which was enhanced in compounds with larger nitrogen substituents. Appropriate choice of such derivatives led to highly potent compounds selective for 5-HT1A sites compared with their activity at other 5-HT and/or adrenergic receptors. The pharmacological profile of compounds which appear to act as agonists at 5-HT1A receptors in the central nervous system to lower blood pressure in animal models of hypertension is presented. PMID- 1886080 TI - 5-HT receptors: subtypes and second messengers. AB - Our knowledge about 5-HT (serotonin, 5-hydroxytryptamine) receptors has gained significantly over the recent few years. The discovery of selective ligands and the use of new techniques have led to a significant increase in the number of recognised receptors subtypes. The present status of awareness is largely related to the use of radioligand binding studies, autoradiography, second messenger analysis and more recently, molecular biological techniques. Three main families of 5-HT receptors, of which subtypes have been described, are now accepted. This heterogeneity is further substantiated by the cloning of the cDNA's of three different 5-HT receptors. This article reviews some of the recent developments which led to the characterisation of 5-HT receptor subtypes. PMID- 1886081 TI - Effect of covalent dimer conjugates of angiotensin II on receptor affinity and activity in vitro. AB - Angiotensin II [1-8 or 2-8] analogues and [4-8] fragments were dimerized through the amino- or carboxy-terminal groups in order to try to increase their potency as reported for other hormones. The binding affinity to the angiotensin II receptor subtypes A (A IIA) and B (A IIB) was tested and compared to the potency in rabbit aortic ring. The [2-8] dimers coupled through the N-terminus show no significant change in potency in aortic ring. The [4-8] fragments coupled through the N-terminus are inactive in the ring. They have however a significantly increased affinity for the A IIA receptor, the specific function of which has not yet been reported. When angiotensin II analogues or fragments are coupled through the C-terminus, there was a significant drop in affinity and potency, confirming the importance of the free carboxyl group in position 8 for binding and activity. It is concluded that binding to the A IIB receptor correlates well with the effectiveness in aortic ring. However, in contrast to the beneficial effect reported for a large number of other hormones, dimerization of angiotensin II or its fragments is not accompanied by an increased biological activity in aortic ring. PMID- 1886082 TI - Nicotinic acetylcholine receptors have ligand-specific attachment point patterns. AB - Employing a panel of synthetic peptides as representative structural elements of the nicotinic acetylcholine receptor from Torpedo electric organ, we recently identified three sequence regions of the receptor (alpha 55-74, alpha 134-153 and alpha 181-200) serving as subsites for the binding of high molecular weight antagonists of acetylcholine (Conti-Tronconi et al. 1990). The relative binding affinities to these subsites of alpha-bungarotoxin and three competitive antibodies varied in a ligand-specific fashion. Employing a set of homologous synthetic peptides differing from alpha 181-200 by the exchange of single amino acid residues along the sequence, we now find that ligand binding crucially depends on the presence of particular amino acids within the subsite while others influence binding only marginally if at all. The existence of ligand-specific attachment points may account for the wide range in binding and kinetic parameters, pharmacological specificity and distinct mean open times of the receptor-integral cation channel observed for cholinergic ligands. PMID- 1886083 TI - Differential signal transduction efficacy and biological activity of triprolyl and pentasarcosyl angiotensin II in adrenal cortex and vascular smooth muscle. AB - Two synthetic analogues of angiotensin II (ANG II) with an extended N-terminus, (Sar)5-ANG II and (Pro)3-ANG II, have been tested in vitro for their ability to bind to ANG II receptors, to raise cytosolic free calcium concentration, [Ca++]i, and to induce a biological response in bovine adrenal zona glomerulosa cells and in cultured rat aortic smooth muscle cells. The results indicate that the two analogues did not behave identically in these two target cells for ANG II. On one hand, in the adrenal cortex, (Sar)5-ANG II and (Pro)3-ANG II were very weak agonists and (Sar)5-ANG II could even be used as an antagonist of ANG II-induced aldosterone production. On the other hand, both peptides were almost as potent as ANG II in vascular smooth muscle cells, with respect to signal messenger generation and prostacyclin synthesis. Such peptides may be useful tools in the elucidation of the differences among ANG II receptors from various target tissues. PMID- 1886084 TI - Inhibition of Ca2+ efflux by pyridine nucleotides. AB - The effects of pyridine nucleotides on the Mg-dependent ATP-stimulated Ca2+ pump and on the ATP-independent Na(+)-Ca2+ exchanger were investigated in rat brain synaptic plasma membranes. Both Ca2+ efflux mechanisms are inhibited by pyridine nucleotides, in the order NADPH greater than NADP greater than NADH greater than NAD with IC50 = ca. 3-4 mM for NADP or NADPH and ca. 5 mM for the other pyridine nucleotides in the case of the ATP-driven Ca(2+)-pump, and with IC50 = 8 to 10 mM for the Na(+)-Ca2+ exchanger. Oxidizing agents such as DCIP or FeCN also affect the Ca(2+)-efflux mechanisms. DCIP and FeCN inhibit the ATP-driven Ca2+ pump but not the Na(+)-Ca2+ exchanger. Inhibition of the ATP-dependent Ca2+ pump is optimal when both a reduced pyridine nucleotide and an oxidizing agent (e.g. DCIP or FeCN) were added together. Under similar experimental conditions the pyridine nucleotide-mediated inhibition of the Na(+)-Ca2+ exchanger is partially removed. Therefore Ca(2+)-efflux mechanisms appear to be controlled in part through the redox environment, probably by means of transplasma membrane dehydrogenases. PMID- 1886085 TI - Electrically-induced release of opioid peptides from the guinea-pig myenteric plexus preparation. AB - Preparations of guinea-pig myenteric plexus-longitudinal muscle suspended in Krebs solution were stimulated electrically in the presence of cycloheximide and tetraethylammonium. The amounts of eleven endogenous opioid peptides released into the perifusing Krebs solution were determined and correlated with the decrease in the tissue contents induced by stimulation. For pro-enkephalin fragments the ratio of release to reduction in tissue contents was 29 to 43% for [Met]enkephalin, [Leu]enkephalin, [Met]enkephalyl-RF and [Met]enkephalyl-RGL. With [Met]enkephalyl-RRV-NH2 (BAM-8) the ratio was higher by 50% or more. However, it is of interest that there was no release of the probable precursor [Met]enkephalyl-RRVGRPEWWMDYQ(BAM-18). In this context it may be important that BAM-8 is the only endogenous opioid peptide having -NH2 at the C-terminal. The low tissue levels of pro-dynorphin derived peptide have made estimation of release unreliable. PMID- 1886086 TI - A computer controlled device to facilitate studies of the kinetics of ligand binding: binding of diazepam to bovine brain membranes. AB - A device to facilitate kinetic receptor filtration assays is described. The receptor containing membranes and the labeled ligand are placed in two separate syringes and are rapidly mixed into a collecting syringe using a pneumatic ram. Shortly after the start of mixing, a pneumatically controlled valve switches the collecting syringe containing the receptor-ligand mixture to the filtration unit. Filtration is performed on glass/microfiber filters or equivalent by pushing the plunger of the collecting syringe by a stepper motor. A valve positioner controlling several valves allows the filtered membranes to be washed and dried by pressure in any user programmable sequence. Further filtration of the receptor ligand mixture can be programmed at selected time points. The entire system is controlled by an IBM-PC. With this system, the association and dissociation of diazepam from crude bovine-brain membranes has been studied at 4 degrees C. The dissociation shows a biphasic pattern with half lifes of 1.3 and more than 23 minutes respectively. Association appears to be into a single compartment. PMID- 1886087 TI - Genetic manipulation of mammals and its application in reproductive biology. PMID- 1886088 TI - Effects of reducing the remating interval after parturition on the fertility and plasma concentrations of luteinizing hormone, prolactin, oestradiol-17 beta and progesterone in lactating domestic rabbits. AB - Primiparous crossbred does were remated on Day 1 (n = 15) or 14 (n = 25) post partum and killed on Day 10 post coitum to assess their fertility. Blood samples were taken during the pre- (0-12 h post coitum) and post- (1-10 days post coitum) ovulatory periods and plasma was assayed for luteinizing hormone (LH), prolactin, oestradiol-17 beta and progesterone. Ovulation response was significantly greater (P less than 0.01) and ovulation rate significantly lower (P less than 0.001) in does mated on Day 1 than in those mated on Day 14 post partum. Does failing to ovulate on Day 14 post partum exhibited no preovulatory LH surge and had significantly lower (P less than 0.05) premating concentrations of oestradiol-17 beta and prolactin than those ovulating at this time. No significant differences in hormone concentrations were observed during the preovulatory period between does ovulating on Days 1 and 14 post partum, with the exception of oestradiol-17 beta. Concentrations of this hormone were significantly lower (P less than 0.01) in does mated on Day 1, at 1 h post coitum. We conclude that (i) fertility was affected by the remating interval after parturition, (ii) ovulation failure was associated with an absence of the preovulatory LH surge and a reduction in premating concentrations of oestradiol-17 beta and prolactin and (iii) the lower ovulation rate in early lactation was apparently caused by a reduction in ovarian competence to respond to the gonadotrophic stimulus. PMID- 1886089 TI - Content of significant amounts of a cytotoxic end-product of lipid peroxidation in human semen. AB - (E)-4-Hydroxy-2-nonenal (HNE), a cytotoxic end-product of lipid peroxidation, is present in significant amounts in human semen (0.902 +/- 0.190 microM; mean +/- s.e.; n = 18). The addition of the divalent cation ionophore A23187 to suspensions of human spermatozoa resulted in increased production of HNE. Exogenous HNE was powerfully spermicidal and as little as 50 microM caused an irreversible loss of motility of human spermatozoa within minutes. The addition of human seminal plasma protected spermatozoa from the toxic effects of HNE. PMID- 1886090 TI - Inhibition by diethylstilboestrol of proliferative potential of follicles of different sizes in immature rat ovaries. AB - Intact immature female rats were treated with 1, 2, 3 or 4 subcutaneous injections of 2 mg diethylstilboestrol (DES)/rat at intervals of 24 h and then killed. Ovaries were collected, cleaned, enzymically digested and serially filtered through Teflon sieves to yield follicles of diameter less than 200 microns (small), 200-400 microns (medium) and greater than 400 microns (large). Follicular supernatant was collected and granulosa cells were extracted from these isolated follicles. There was a general increase in [3H]thymidine incorporation in all sizes of follicles after 1 or 2 DES injections, the increase in the medium and large follicles being significant after 2 doses. With 3 and 4 injections of DES, there was a sudden decrease in the rates of [3H]thymidine incorporation, particularly in the medium-sized follicles, which also had higher concentrations of follicular supernatant protein. Protein contents in small and large follicles did not change significantly. The follicular supernatant protein had a specific and dose-dependent inhibitory effect on [3H]thymidine incorporation when added to cultures of rapidly dividing granulosa cells. Addition of the same amounts of bovine serum albumin (BSA) to the cultures had no effect. Heat-denaturing did not abolish the inhibition by the protein. Removal of the protein from the cultures after the first 48 h resulted in a rebound increase in [3H]thymidine incorporation during the following 48 h, showing that the inhibitory effects were reversible. Though aromatase activity after 1 or 2 DES injections abruptly decreased after 3 and 4 injections, follicular supernatant protein had no effect on steroidogenesis in cultured granulosa cells. Taken together, these findings suggest that oestrogen can inhibit follicular development, depending on the duration of exposure. We propose that the inhibitory effects of DES on cell proliferation are mediated via the synthesis of a specific peptide factor which is produced in high amounts in the medium-sized follicles only, on prolonged exposure to the oestrogen. This factor may be autocrine or paracrine, serving as an in-built autoregulatory control mechanism for follicle development, particularly at pro-oestrus, when oestrogen concentrations are highest. PMID- 1886091 TI - Effect of dietary intake on pattern of growth of dominant follicles during the oestrous cycle in beef heifers. AB - Friesian x Hereford heifers (n = 19; mean +/- s.e.m. body weight (BW) = 375 +/- 5 kg) were used in a randomized incomplete block design. Heifers were fed 0.7 (n = 7; L), 1.1 (n = 7; M) or 1.8% (n = 5; G) of BW in dry matter (DM)/day for 10 weeks. Ovaries were examined by ultrasound, for one oestrous cycle, from week 5 of treatment. Maximum diameter of dominant follicles was smaller (P less than 0.05) in L (11.8 +/- 0.1 mm) than in M (13.7 +/- 0.2 mm) or G (13.2 +/- 0.3 mm) heifers. Growth rate (mm/day) of dominant follicles during the oestrous cycle was not affected (P greater than 0.05) by dietary intake. Persistence of dominant follicles was shorter (P less than 0.05) in L (9.8 +/- 0.2 days) than in M (11.9 +/- 0.3 days) or G (12.7 +/- 0.4 days) heifers. Three dominant follicles were identified during the oestrous cycle of 5 of 7 L, 3 of 7 M and 1 of 5 G heifers (P less than 0.10); 2 dominant follicles were identified in the remaining heifers (n = 2 of 7, 4 of 7 and 4 of 5, respectively). Length of the luteal phase and luteal-phase concentrations of progesterone were not affected (P greater than 0.05) by treatment. Low dietary intake reduced the diameter and persistence of dominant follicles during the oestrous cycle of beef heifers and tended to increase the proportion of oestrous cycles with 3 dominant follicles. PMID- 1886092 TI - Seasonal changes in testicular size, plasma testosterone concentration and body weight in captive flying foxes (Pteropus poliocephalus and P. scapulatus). AB - Adult male flying foxes Pteropus poliocephalus and P. scapulatus were captured in south-east Queensland and kept in outdoor enclosures. Testicular size (TS), plasma testosterone concentrations (PTC) and body weight (BW) were measured over 1-year periods. Testicular recrudescence in P. poliocephalus began before the summer solstice and TS was greatest during mid-March (autumn) and lowest from July to September. Large increases in PTC were observed in all individuals approximately 1 month after the peak in TS. BW also increased around the time of the mating season, changes being correlated significantly with changes in TS. Mating occurred between April and June, and births from late October to late November. In P. scapulatus, TS was greatest in the spring (October) and least in the autumn (February to May); PTC fluctuated throughout the year in this species but, unlike P. poliocephalus, did not show a single large increase in the mating season. BW showed a similar seasonal pattern to that seen in P. poliocephalus, being greatest at the time of greatest TS. Mating occurred in October to November, and births in autumn. In captivity, in outdoor enclosures, these species maintained the seasonal reproductive patterns observed in the wild. The 2 species respond differently to the same environmental cues in terms of regulation of the timing of their breeding seasons. PMID- 1886093 TI - Mating-associated peak in plasma testosterone concentration in wild male grey headed flying foxes (Pteropus poliocephalus). AB - Plasma testosterone (T) concentrations, measured in wild bats of P. poliocephalus in Queensland in 1983-87, showed a peak during the mating season in March. Plasma androstenedione (A) concentrations changed less dramatically with season. Mean testicular concentration and total content of T and A was substantially greater in March than in regressed testes in July-October. Paired adrenal glands were heavier during February to April than during September to November. In the same wild population, throughout a single breeding season (1987), plasma T concentrations were significantly higher in mid-March than 3 weeks previously or 3 weeks later. Testicular T content rose as the breeding season progressed, being greatest during March, coinciding with the large rise in plasma T concentrations. Testicular T concentration and content were correlated significantly with plasma T concentrations. Adrenal glands contained T, but the absolute concentrations were much lower than in the testis. No significant changes in plasma, testicular or adrenal A concentrations were found as the breeding season progressed. The large increase in plasma T during the mating season appears to be due to increased testicular production. PMID- 1886094 TI - A study of the effect of high concentrations of fluoride on the reproductive organs of male rabbits, using light and scanning electron microscopy. AB - Fluoride was orally administered to rabbits at 10 mg NaF/kg body weight for 18 or 29 months. The animals were then killed and the structure of the testis, epididymis and vas deferens studied under light and scanning electron microscopes. In animals treated for 29 months, the spermatogenic cells in the seminiferous tubules were disrupted, degenerated and devoid of spermatozoa. In animals treated for 18 or 29 months, loss of cilia on the epithelial cells lining the lumen of the ductuli efferentes of the caput epididymidis and of stereocilia on the epithelial cells lining the lumen of the vas deferens was observed. In some regions of the epithelial lining of the lumen of the ductuli efferentes and vas deferens, the boundaries of the cells were not clear and appeared to be peeled off. Mucus droplets were abundant in the vas deferens of control animals, but absent in both the treated groups. Spermatogenesis ceased only in animals treated for 29 months. The difference in the structural changes observed in the testes of the 2 treated groups may have been due to the blood-testis barrier. It is concluded that ingestion of high concentrations of fluoride has harmful effects on the male reproductive system. PMID- 1886095 TI - Evidence that the seasonal antler cycle of adult Reeves' muntjac (Muntiacus reevesi) is not associated with reproductive quiescence. AB - Data were obtained from post-mortem investigations of 190 culled and road-killed muntjac bucks between 1967 and 1989. Although adult bucks (i.e. those having undergone at least one antler cycle) have a synchronous annual antler cycle, unlike temperate-zone cervids there was little seasonal variation in testis size or activity, or in the size and activity of the epididymidis or accessory reproductive glands. Spermatogenesis was not abated when the antlers were in velvet and year-round fertility was achieved without additional sperm storage. There was little seasonal change in plasma testosterone concentrations in samples obtained from captive and free-living bucks although castration caused antler casting and prevented mineralization. Hence the data are equivocal as to the role of steroids in driving the antler cycle; experimental work on this species would be valuable in examining the mechanisms which regulate the antler cycle. PMID- 1886096 TI - Suppression of ovarian activity during the breeding season in suckling Japanese monkey (Macaca fuscata). AB - The menstrual cycle was examined in Japanese monkeys, short-day breeders, with or without nursing babies during the breeding season by determining the change in the plasma concentration of progesterone. Blood samples were obtained weekly from suckling and nonsuckling mothers for 6 months from September to February. Plasma concentrations of progesterone in suckling mothers did not show any apparent fluctuation and remained low throughout the study, while irregular menstruation was observed. In nonsuckling mothers, cyclic changes in plasma progesterone concentration accompanied by regular menstruation occurred from October. Annual birth rates were lower in monkeys housed in individual cages (17.6%) than in free ranging monkeys in Miyajima colony, near Hiroshima in Japan (37.5%). These results indicate that the suckling stimulus for females with young born in spring is potent enough to suppress ovarian activity during the autumn breeding season. PMID- 1886097 TI - Influence of oxytocin infusion during oestrus and the early luteal phase on progesterone secretion and the establishment of pregnancy in ewes. AB - In Experiment 1, an osmotic minipump containing oxytocin was implanted s.c. in ewes for 12 days beginning on Day 10 of the oestrous cycle, producing approximately 100 pg oxytocin/ml in the plasma. Two days after the start of infusion, all ewes were injected with 100 micrograms cloprostenol and placed with a fertile ram. At slaughter 22 days later, 9 (75%) of the 12 control (saline infused) ewes were pregnant compared with 1 (11%) of the 9 ewes infused with oxytocin. In the control group, midcycle plasma concentrations of oxytocin were significantly higher in nonpregnant than in pregnant ewes. In Experiment 2, an infertile ram was used throughout to avoid any possible effects of pregnancy and oxytocin infusions were given at different stages of the oestrous cycle. Otherwise the protocol was similar to that in Exp. 1. Oxytocin infusion during luteolysis and the early follicular phase had no effect on the subsequent progesterone secretion pattern, but infusions beginning the day before cloprostenol-induced luteolysis and lasting for 7 or 12 days and infusions beginning on the day of oestrus for 4 days all delayed the subsequent rise in plasma progesterone by approximately 3-4 days. In these animals, the cycle tended to be longer. It was concluded that an appropriate oxytocin secretion pattern may be necessary for the establishment of pregnancy in ewes and that a high circulating oxytocin concentration during the early luteal phase delays the development of the young corpus luteum. PMID- 1886099 TI - Seasonal control of odour preferences of meadow voles (Microtus pennsylvanicus) by photoperiod and ovarian hormones. AB - During the spring-summer breeding season, female meadow voles prefer odours of males over those of females, but in the autumn-winter season of reproductive quiescence this preference is reversed. Females housed in long (14 h light/day) and short (10 h light/day) photoperiods, respectively, had odour preferences comparable to those of spring and autumn voles, respectively. The preference of long-photoperiod voles for male over female odours was reversed by ovariectomy and restored by treatment with oestradiol. By contrast, neither ovariectomy nor oestradiol affected odour preferences of short-photoperiod voles. Long days appear to influence olfactory preferences by altering ovarian hormone secretion. The failure of oestradiol to affect odour preferences in short photoperiods suggests that the neural substrates mediating this behavioural response are refractory to oestrogens during the nonbreeding season. PMID- 1886098 TI - Rapid extraction of faecal steroids for measuring reproductive cyclicity and early pregnancy in free-ranging yellow baboons (Papio cynocephalus cynocephalus). AB - A rapid method was developed for extracting and assaying oestradiol and progesterone in faeces (n = 242) of female yellow baboons, free-living in Tanzania. Dose response studies generated slopes of 1.02 (r2 = 0.99) for oestradiol and 1.09 (r2 = 0.99) for progesterone, suggesting that this method accurately measured these steroids in faeces. Parallelism was proved by demonstrating that slopes produced from serially diluted samples were not different from those generated from standard curves (mean P value = 0.53 +/- 0.17 for oestradiol and 0.44 +/- 0.13 for progesterone). Faecal progesterone concentrations measured over several cycles in 2 females increased and decreased in correspondence to visual markers of the luteal phase (i.e. the period between sex-skin detumescence and menses), but the presumed preovulatory oestradiol peak was not observed consistently in all cycles. Progesterone profiles during early to midgestation in 3 females confirmed pregnancy by 25 days (14%) of gestation. Oestradiol profiles were more variable and were not indicative of pregnancy until 40 days (22%) of gestation. Radiolabel-infusion studies revealed that 32% of progesterone (n = 2) but only 11% of oestradiol (n = 2), was cleared through faeces. The latter findings may account for the greater variation observed in temporal oestradiol patterns during the baboon menstrual cycle and pregnancy. Compared with previous techniques, these new methods (i) save considerable time in assaying raw material and (ii) result in high extraction recoveries of faecal steroids (approximately 88% for oestradiol and 91% for progesterone). This approach may be particularly useful for studying physiological function and endocrine-environmental interrelationships in free-living primate species. PMID- 1886101 TI - Follicular dynamics and temporal relationships among body temperature, oestrus, the surge of luteinizing hormone and ovulation in Holstein heifers treated with norgestomet. AB - The effects of chronic treatment with norgestomet on follicular dynamics, corpus luteum growth and function as well as the temporal relationships among body temperature, oestrous behaviour, the luteinizing hormone (LH) surge and ovulation following implant removal were studied in 16 Holstein heifers. Oestrous cycles of the heifers were initially synchronized using 2 injections of prostaglandin F-2 alpha (PGF-2 alpha) 12 days apart. The heifers were then implanted with a norgestomet ear implant for 9 days, beginning either at the middle of the synchronized cycle (dioestrus) or at the end of the synchronized cycle (pro oestrus). Follicular dynamics, corpus luteum growth and regression, and plasma progesterone were not affected by norgestomet treatment at dioestrus. The dominant follicle present at the time of norgestomet implantation in the pro oestrus group was maintained during the 9-day implant period of 6 of 8 heifers and ovulated after implant removal. Time from implant removal to onset of standing oestrus and time to LH peak following implant removal were highly correlated with the time of ovulation (r = 0.92 and 0.96, respectively). Onset of standing oestrus and the LH peak and the onset of standing oestrus and peak vaginal and rectal temperatures were also highly correlated (r = 0.96, 0.82 and 0.81, respectively). It is concluded that any decrease in pregnancy rates following treatment with norgestomet is not due to asynchrony among oestrus, the LH surge and ovulation. PMID- 1886100 TI - Antibodies to early pregnancy factor retard embryonic development in mice in vivo. AB - Previous work in this laboratory has shown that passive immunization of mice against early pregnancy factor (EPF) leads to failure to maintain pregnancy. The findings presented in this paper demonstrate that this treatment affects the development of the embryos very early in gestation. By Day 3, 54 and 25% of embryos in the 2 groups treated with anti-EPF immunoglobulin (Ig)G and IgM, respectively, had not developed to the 4-cell stage, compared with 12 and 1% in the control groups. None of the embryos in the mice treated with anti-EPF had developed beyond the 8-cell stage. A similar delay in development after treatment was observed on Day 4. The effect apparent during the early stages of cleavage is an indirect rather than a direct one, as 2-cell embryos (32-36 h post coitum), cultured in vitro in the presence of anti-EPF antibodies, developed uninterrupted to the morula and blastocyst stage. The delay in development did not appear to be caused by a disruption of the normal pattern of circulating progesterone, as progesterone concentrations on Day 4 were within the normal range for Quackenbush mice. PMID- 1886102 TI - Direct effect of angiotensin II on in-vitro perfused rabbit ovary. AB - The effects of angiotensin II (AII) and its receptor blocker, saralasin (SAR), on ovulation and oocyte maturation were investigated in an isolated, in-vitro perfused rabbit ovary. Ovulation and oocyte maturation were induced by AII in the absence of human chorionic gonadotrophin (hCG). SAR inhibited ovulation induced by AII or hCG, but not oocyte maturation. AII appears to play a critical role in follicle rupture, but not in resumption of oocyte meiosis. PMID- 1886103 TI - Survival of bovine embryos transferred to progesterone-treated asynchronous recipients. AB - Treatment of recipient cows with 100 mg of progesterone daily from Days 1 to 5 of the oestrous cycle increased plasma progesterone compared with vehicle-treated recipients. Embryo transfer to progesterone-treated recipients which showed oestrus 72 h after the donor cows resulted in pregnancy rates at Day 35 similar to those of synchronous (+/- 12 h) recipients (42 vs. 50%). Only 1 of 22 (4.8%) asynchronous (-72 h) vehicle-treated recipients established pregnancy. Similar treatments of cyclic cows with progesterone shortened (P less than 0.01) the interoestrous interval by 3.2 days. When assessed on Day 7 of pregnancy, administration of progesterone to superovulated donor cows on Days 1-4 of pregnancy did not affect early embryo development compared with superovulated cows treated with vehicle alone. Plasma progesterone increased rapidly in superovulated cows compared with cows during the oestrous cycle. The results indicate that administration of progesterone early in the oestrous cycle of the recipient can effectively advance uterine receptivity for the transfer of older asynchronous embryos. PMID- 1886104 TI - Failure to detect platelet-activating factor using the splenectomized mouse bioassay. AB - The ability of purified preparations of platelet-activating factor (PAF), from three different suppliers, to induce thrombocytopaenia in mice after splenectomy and to activate mouse platelets in vitro was examined. Although the PAF preparations were potent activators of horse and cow platelets in vitro, injections of up to 1 microgram PAF failed to elicit thrombocytopaenia responses in either CD1 or Swiss Webster random-bred mice. However, when thrombin was injected into Swiss Webster mice, a dose-dependent decrease in the concentration of platelets was observed. Furthermore, isolated platelets from these strains and from 3 inbred lines (C3H/He, BALB/c, C57BL/6) of mice, were not aggregated by PAF in vitro but were sensitive to adenosine diphosphate and thrombin. No change in circulating platelet concentrations was observed over the initial 7 days of gestation in intact Swiss Webster and C57BL/6 or splenectomized C57BL/6 mice, suggesting either an absence of PAF production during early pregnancy in these strains or insensitivity of their platelets to PAF. These results suggest that many mouse strains are unsuitable for the bioassay of PAF. PMID- 1886105 TI - Chorionic gonadotrophin and embryo-maternal recognition during the peri implantation period in primates. AB - Genes for chorionic gonadotrophin (CG) are transcribed by the 16-cell embryo stage in humans, but there is no clear evidence of CG secretion as a bioactive dimer before attachment and trophoblast outgrowth stages of implantation. The studies summarized question the timing of CG expression and secretion, the possible roles of CG for intraembryonic differentiation and at the implantation site, and the recognition of this primate embryo-derived signal in support of the corpus luteum. The data suggest that the implantation window in primates may be broader than in non-primate species, where a closer synchrony between embryonic, tubal and uterine events appears to be necessary for embryonic survival. Some preliminary data concerning an association between peripheral thrombocytopenia, ovarian inhibin secretion and peri-implantation stages of embryo development indicate that an unknown embryonic signal may be secreted before bioactive CG can be detected. PMID- 1886106 TI - Dissociation of corpus luteum, endometrium and blastocyst in human implantation research. AB - We describe a well-established approach for studying the parameters and mechanisms of synchronization or desynchronization between the maternal and embryonic systems before implantation. It is useful for inducing 'delayed secretion' of the endometrium by different endocrine interventions, which dissociate the endometrial transformation from its control by the corpus luteum. The technique has been achieved by means of direct progesterone antagonists which competitively bind to the progesterone receptor and, in turn, inhibit the physiological effects of progesterone. During the luteal phase, secretory protein patterns indicate the receptive stage of the endometrium. Evidence is presented to show that these patterns, analysed by electrophoresis and densitometry, define the time at which an embryo transfer is promising for implantation and establishment of pregnancy. PMID- 1886107 TI - Glycans as biochemical markers of human endometrial secretory differentiation. AB - Uterine fluid contains a mixture of glycoprotein components the quantity and composition of which vary during the menstrual cycle. Their analysis may give clues to the involvement of maternally derived components in modulating the state of the peri-implantation blastocyst and aid in assessing the differentiation of the endometrium in preparation for implantation. Endometrial epithelium also exhibits an apical glycocalyx, the composition of which varies with the state of tissue differentiation. Evidence from animal systems suggests that glycans may be involved in molecular recognition between the embryo and maternal surface at implantation. Lectins and monoclonal antibodies to glycan epitopes have been used as sensitive and specific probes to examine the carbohydrates associated with endometrial epithelium as a function of the ovarian cycle. Numerous glycan structures are detected specifically in epithelial cells. Hitherto unsuspected biosynthetic heterogeneity is present in the glands. A secretory sialokeratan sulphate epitope is described, the occurrence of which coincides with the implantation phase of the cycle. PMID- 1886108 TI - Human endometrial morphology around the time of implantation in natural and artificial cycles. PMID- 1886109 TI - Normal and abnormal implantation in spontaneous in-vivo and in-vitro human pregnancies. PMID- 1886111 TI - Prevention of drowning. PMID- 1886110 TI - Does malaria select for predisposition to autoimmune disease? PMID- 1886112 TI - The psychoses of epilepsy. PMID- 1886113 TI - Neuropsychological investigation of temporal lobe epilepsy. PMID- 1886114 TI - Disconnected awareness for detecting, processing, and remembering in neurological patients. PMID- 1886115 TI - 'Hysteria', 'functional' or 'psychogenic'? A survey of British neurologists' preferences. AB - The diagnostic preferences of British neurologists for patients who lack a physical explanation for their symptoms were assessed by means of a postal questionnaire. Analysis of 168 completed replies showed 'functional', 'psychogenic' and 'hysteria' to be the most popular terms in use. The number of different terms a clinician would use rose in line with the volume of such patients they encountered, but was unrelated to clinician factors such as the extent of their clinical experience in psychiatry. A specific enquiry into these respondents' interpretation of the term 'functional' revealed a clear consensus as to which syndromes it should apply to, although this consensus was not shared by a comparison group of psychiatrists. PMID- 1886116 TI - Preanaesthetic medication: a survey of current usage. AB - A survey has been carried out amongst the UK based members of the Association of Anaesthetists of Great Britain and Ireland regarding their practice of premedication. Ninety-three per cent of respondents (reply rate 51.7%) used sedative-hypnotic premedication routinely in adults and 84% in children. However, anticholinergic premedication was used by only 36% in adults and 56% in children. Temazepam was the most frequently used sedative premedicant in adults and trimeprazine in children. Atropine and hyoscine were the most frequently used anticholinergic drugs. The main reasons for using sedative-hypnotic premedication were allaying anxiety and providing sedation. The main reasons for using anticholinergic drugs were drying of secretions and protection against vagal overactivity. This survey concludes that while sedative-hypnotic premedication continues to be used in the majority of patients with oral benzodiazepines the most frequently used drugs, the use of anti-cholinergic premedication continues to decline. PMID- 1886117 TI - The changing pattern of thoracic surgery in the United Kingdom 1963-1982. AB - During the period 1963-1982 a total of 11,459 patients with general surgical and thoracic conditions were admitted to the Churchill and John Radcliffe Hospitals in Oxford under the care of a single thoracic surgeon. 55.1% of the admissions were for general surgical conditions whereas 44.9% were for a thoracic disorder. The total period has been studied by dividing it into three subgroups of 7, 6 and 7 years (1963-1969, 1970-1975, 1976-1982). The percentage of thoracic patients treated during the three periods was found to be 48.86%, 41.73% and 50.11% respectively. The three periods studied have been subdivided into major disease groups and the changes in these groups have been studied in detail. During this 20-year period there has been a dramatic change in the makeup of a typical thoracic surgical practice. This is in part due to the changing pattern and prevalence of many of the diseases treated by thoracic surgeons, but is also due to a change in referral patterns, the distribution of patients between thoracic and general surgeons and also the dichotomy emerging between thoracic and cardiac surgeons. PMID- 1886118 TI - The audit of cervical cytology screening programmes: discussion paper. PMID- 1886119 TI - Treatment of Parkinson's disease in 'Ayurveda' (ancient Indian system of medicine): discussion paper. PMID- 1886120 TI - Anoxic asphyxia--a cause of industrial fatalities: a review. AB - The investigation of commercial diving accidents has indicated that the danger of anoxia, from the inhalation of gases not containing oxygen, is not fully recognized. The problem is more common in a variety of general industrial situations and is an occasional cause of death in anaesthesia. It is a particular hazard with inert gases, which, because they are recognized to be non-toxic, give a false sense of security. The pathological findings consist of pulmonary oedema and petechial haemorrhages, mainly in the brain, lungs and myocardium. Whenever possible, a minimum oxygen content should be included in all gases liable to be respired, but where this is not possible, oxygen analysers and alarms should be provided. Where a general hazard exists, personnel must be warned of the danger. PMID- 1886121 TI - A young woman with spotty pigmentation, acromegaly, acoustic neuroma and cardiac myxoma: Carney's complex. PMID- 1886122 TI - Renal cell carcinoma presenting in the skin. PMID- 1886123 TI - Liposarcoma of the spermatic cord. PMID- 1886124 TI - Neuroleptic malignant syndrome: a diagnostic dilemma. PMID- 1886125 TI - Contralateral hemiplegia complicating herpes zoster ophthalmicus. PMID- 1886126 TI - Pregnancy occurring in a morbidly obese woman who had undergone gastric stapling. PMID- 1886127 TI - Clinical considerations on neuroleptic malignant syndrome. PMID- 1886128 TI - Percutaneous transluminal coronary angioplasty in the treatment of patients with multivessel coronary artery disease. PMID- 1886129 TI - Accident flying squads and emergencies. PMID- 1886130 TI - Accident proneness. PMID- 1886131 TI - Long-term benzodiazepine use and pain. PMID- 1886132 TI - Adenocarcinoma of the gallbladder. PMID- 1886133 TI - Cardiac resuscitation; a panacea or an ethical decision? PMID- 1886134 TI - Wire-guided balloon coloplasty--a new treatment. PMID- 1886135 TI - Intentional replantation. PMID- 1886136 TI - Angiotensin II-binding protein in adult and neonatal rat heart. AB - An angiotensin II-binding activity has been identified in the 100,000 x g supernatant fraction of adrenal gland, kidney, liver, heart and brain of adult rat. The binding is specific for angiotensin II; it is of high affinity and completely dependent upon the presence of an organomercurial, p chloromercuriphenylsulfonic acid. Reducing agents, on the other hand, cause a dissociation of bound ligand. Covalent cross-linking of [125I]-angiotensin II to the soluble fraction from rat heart followed by SDS-polyacrylamide gel electrophoresis and autoradiography indicated that the macromolecule that binds angiotensin II is most probably a protein with an apparent mass of 78,000 dalton. A comparison of the binding of angiotensin II to the 100,000 x g supernatant fraction from both neonatal (1-3-day-old) and adult (3-month-old) rat hearts revealed that angiotensin II binds with similar affinity and specificity, but the number of binding sites is 3-fold higher in the neonatal heart (KD and Bmax were 10.4 +/- 3.1 nM and 1.6 +/- 0.4 pmol/mg protein for adult and 8.8 +/- 2.9 nM and 4.9 +/- 0.7 pmol/mg protein for neonatal heart, respectively). The membrane fraction prepared from neonatal rat heart similarly bound angiotensin II in a saturable manner and with high affinity (KD 4.3 +/- 0.5 nM and Bmax 146.4 +/- 4.9 fmol/mg protein), but a similar membrane fraction prepared from adult rat heart failed to show any angiotensin II binding. These observations indicated that, in rat heart, there is a decrease of angiotensin II-binding sites, both soluble and membrane bound, with age. Hence, rat heart, at various stages of development, and myocytes prepared from it should provide a suitable system with which to study the developmental regulation of the angiotensin II-binding protein. PMID- 1886137 TI - Molecular cloning and developmental expression of the rat cardiac-specific isoform of troponin I. AB - Troponin I is the subunit of the troponin complex in striated muscle which inhibits actomyosin ATPase activity. We have isolated a full-length cDNA clone for rat cardiac troponin I and determined its nucleic acid sequence. The amino acid sequence deduced from this clone shows 88%-92% similarity with previously reported amino acid sequences for rabbit (Wilkinson and Grand, 1978) and bovine (Leszyk et al.) cardiac troponin I. Examination of cardiac troponin I mRNA abundance during development revealed a 15-fold induction in its expression in the adult heart compared to that in embryonic (14 day) heart muscle. Furthermore, expression of cardiac troponin I mRNA was restricted to heart muscle and was not detected in skeletal muscle at any developmental stage. PMID- 1886138 TI - Asparaginyl deamidation-methylation of rat ventricular myosin light chains. AB - Spontaneous asparaginyl deamidation can produce damage to cytoskeletal proteins, and may lead to their targeting for subsequent rapid intracellular breakdown or repair. To test if myofibrillar proteins are subject to spontaneous deamidation damage in vitro, purified rat ventricular myosin light chain 1 (MLC1v) and phosphorylatable myosin light chain 2 (MPLC2v) were incubated (37 degrees C, 4 h, pH 2-11), and tested as substrates for human erythrocyte and rat cardiac protein carboxyl methyltransferase (PCMT). PCMT catalyzes the transfer of a methyl group from [3H-methyl] S-adenosyl methionine to deamidated asparaginyl residues and altered aspartyl residues on damaged proteins. MLC1v and MPLC2v underwent extensive incubation damage at neutral and alkaline pH. Sodium dodecyl sulfate polyacrylamide gel electrophoresis and fluorography revealed 3H-incorporation into MLC1v, MPLC2v, and a Mr = 14,000 polypeptide. 3H-methylated, CNBr-cleavage fragments of PCMT-methylated light chains were then separated by reverse-phase high performance liquid chromatography, and sequenced by automated Edman degradation. The major 3H-labeled peptide of the Mr = 14,000 protein proved homologous to residues 84 to 104 of rat MPLC2v, with a proposed deamidation site at Asn99-Ala100. The major 3H-labeled peptide from MLC1v proved homologous to residues 73 to 111 of rat cardiac MLC1v, with a proposed deamidation site at Asn108-Ser109. These results indicate that both myofibrillar protein subunits undergo selective non-enzymatic degradation at neutral and alkaline pH, resulting in the formation of methyl acceptor sites for human erythrocyte and rat cardiac PCMT. PCMT-catalyzed methylation of ventricular myosin light chains may be important in the repair, or subsequent proteolysis of these long-lived structural proteins of the myofibril. PMID- 1886139 TI - Discordance between accumulation of C-14 deoxyglucose and Tl-201 in reperfused myocardium. AB - Radiolabeled deoxyglucose (FDG) has been advocated as a marker of viability of reperfused myocardium during acute infarction. However, data for such recommendation are few. We investigated cardiac deposition of C-14 deoxyglucose (C-14 DG) and of Thallium -201 (Tl-201) in rabbits subjected to coronary occlusion (15, 30, 60 or greater than 100 min) and reperfusion (75 min and 24 h). Measured myocardial concentrations of C-14 DG and Tl-201 in macroautoradiograms were quantitatively correlated in a 24 h reperfusion group with presence of myocardial necrosis evaluated by light microscopy. The major finding in this investigation was that with 30 min or 60 min of ischemia followed by reperfusion there were myocardial regions with significant hypoperfusion (Tl-201) and histologic necrosis. However, in the same myocardial areas, the deposition of C 14 DG was not correlated with the extent of necrosis (r = 0.27). Also, the deposition of C-14 DG in acute myocardial infarction was higher than that of Tl 201 (P = 0.05 by paired T test and by nonparametric Wilcoxon's test). It was also demonstrated that when the occlusion time was varied (15-130 min) and early reperfusion was provided for 75 min or omitted altogether, the myocardial accumulation of Tl-201 was variable and that myocardial sequestration of C-14 DG was higher than perfusion in central and peripheral portions of the area-at-risk. These observations do not support a role for the use of radiolabeled deoxyglucose for the detection of myocardial viability in recently infarcted cardiac muscle. PMID- 1886140 TI - Dual action of prajmalium on the Ca currents in frog isolated cardiomyocytes. AB - The effects of N-n-propylajmaline (prajmalium) on the Na and Ca currents of single frog atrial and ventricular cells were studied by means of the whole-cell patch-clamp technique. Prajmalium (10(-9) to 10(-6) M) depressed the Na current (INa) in a dose- and use-dependent manner. In the same range of concentrations, prajmalium induced a dual effect on the high (ICaL) and low (ICaT) threshold Ca currents (the latter being only present in atrial cells). At a low concentration (10(-9) M), prajmalium increased both Ca currents while at high concentrations (10(-6) M) it depressed them. Prajmalium appeared very potent on ICaT although this current is generally reported to be barely sensitive to agonists and drugs. The action of the drug was also accompanied by a shortening in the half-time of inactivation of the Ca currents and a slight hyperpolarizing shift of their availability curves. The increase in ICaL by prajmalium was not prevented by prazosin (10(-7) M) nor by propranolol (10(-6) M), and it was also observed after ICaL had been fully stimulated by isoproterenol (10(-7)M). Nifedipine (10(-6) M), however, was able to prevent or block the prajmalium-induced increase in ICaL. Some similarities between the actions of prajmalium and dihydropyridine agonists on Ca currents are discussed. PMID- 1886141 TI - Modification of cardiac ionic currents by photosensitizer-generated reactive oxygen. AB - The effects of reactive oxygen species (ROS) generated by light and the photosensitizer Rose Bengal on ionic currents in single frog atrial cells were investigated. The excitatory inward sodium and calcium currents were both suppressed by ROS as was the outward, delayed rectifier potassium current. The inactivation kinetics of the sodium current were slowed markedly whereas the kinetics of calcium current inactivation were much less affected and potassium current activation was not changed. The sodium current-voltage relationship was shifted in the depolarizing direction by ROS whereas the voltage-dependencies of both the calcium and potassium currents were not affected. In addition to suppressing the time- and voltage-dependent sodium, calcium, and potassium currents, ROS enhanced a time-independent current which was outwardly directed at positive membrane potentials. However, the induction of this time-independent current required longer ROS exposure than was required to significantly suppress the other currents. The rapid onset of ROS-induced suppression of calcium and potassium currents followed by a later enhancement of a time-independent current can explain ROS-induced changes in action potential duration. Brief ROS exposure increased action potential duration whereas longer exposure reduced action potential duration. PMID- 1886142 TI - Combating smoking in the United States: progress through science and social action. PMID- 1886143 TI - Promising cancer drug has a different price for every use. PMID- 1886144 TI - Cancer out of the closet: support emerges over two decades. PMID- 1886145 TI - Investigators, insurers consider marrow transplant issues. PMID- 1886146 TI - Consumer group report examines mammography standards. PMID- 1886147 TI - Smoking-attributable cancer mortality in 1991: is lung cancer now the leading cause of death among smokers in the United States? AB - Findings from the new American Cancer Society prospective study of 1.2 million men and women indicate that mortality risks among smokers have increased substantially for most of the eight major cancer sites causally associated with cigarette smoking. Lung cancer risk for male smokers doubled, while the risk for females increased more than fourfold. On the basis of the new American Cancer Society relative risks, we project that cigarette smoking alone will contribute to slightly more than 157,000 of the 514,000 total cancer deaths expected to occur in the United States in 1991. Overall, smoking directly contributes to 21.5% of all cancer deaths in women but 45% of all cancer deaths in men. It would also appear that lung cancer has now displaced coronary heart disease as the single leading cause of excess mortality among smokers in the United States. PMID- 1886148 TI - Phase I and clinical pharmacological evaluation of aphidicolin glycinate. AB - The toxicity profile and the pharmacokinetics of aphidicolin glycinate, a water soluble analogue of aphidicolin, have been evaluated in two consecutive phase I clinical studies. In the first study, aphidicolin glycinate was given by 1-hour infusion for 5 consecutive days, every 3 weeks (daily x 5 study); in the second study, which was planned on the basis of the pharmacokinetic information obtained in the previous study, the drug was given by 24-hour continuous infusion. Treatment was repeated every 3 weeks. In the daily x 5 study, the daily dose was escalated from 12 mg/m2 to the maximum tolerated dose of 2250 mg/m2. Local toxicity was dose limiting. Elimination half-life was 2 +/- 0.2 hours (mean +/- SE) with aphidicolin being undetectable 6-8 hours after the end of the infusion. In the 24-hour continuous-infusion study, the dose was escalated from 435 mg/m2 to the maximum tolerated dose of 4500 mg/m2. Local toxicity was dose limiting, while other toxic effects were absent. The experimentally determined concentrations at the steady state were in agreement with those predicted on the basis of the available pharmacokinetic data. The targeted concentration at the steady state of 3 micrograms/mL was achieved at doses greater than or equal to 3000 mg/m2. Twenty-four-hour continuous infusion is the recommended schedule for clinical evaluations of aphidicolin glycinate as the synchronizing agent or in combination with cisplatin. PMID- 1886149 TI - Expression of transforming growth factor-beta 1 in human non-Hodgkin's lymphoma xenografts. PMID- 1886150 TI - Impact of mammography on breast cancer incidence in Vaud, Switzerland. PMID- 1886151 TI - Aspirin use and incidence of large-bowel cancer in a California retirement community. PMID- 1886152 TI - How physicians handle drug investigations. PMID- 1886154 TI - Smoking with the enemy: tobacco council funds scientists. PMID- 1886153 TI - New diagnostics unveil cancers by visual and molecular means. PMID- 1886155 TI - Fossil tumor creates interest in prehistoric cancers. PMID- 1886156 TI - Traffic radar and cancer: smoking gun? PMID- 1886157 TI - Contralateral primary tumors in breast cancer patients in a randomized trial of adjuvant tamoxifen therapy. AB - Prophylactic treatment with the anti-estrogen tamoxifen may reduce the risk of breast cancer because estrogens are thought to act as promoters in the pathogenesis of the disease. This article presents results on the incidence of contralateral new primary tumors among 1846 postmenopausal breast cancer patients included in a randomized trial of adjuvant tamoxifen therapy for 2 or 5 years after surgery versus no adjuvant endocrine therapy. The median follow-up was 7 years (range, 3-13 years). There was a significant reduction of contralateral breast cancer in the 931 patients in the tamoxifen group versus that in the 915 control patients (29 versus 47 cases, respectively; P = .03). The cumulative incidence at 10 years in the tamoxifen group and the control group was 5% and 8%, respectively. Analysis of the relative hazard of contralateral tumor over time showed that the benefit with tamoxifen therapy was greatest during the first 1-2 years, but there was a continued risk reduction during the entire follow-up period, i.e., more than 10 years after cessation of treatment. There was no significant difference in the number of contralateral cancers in the patients randomly assigned to 2 or 5 years of treatment, but the 95% confidence interval of the relative hazard was wide. The proportion of estrogen receptor-negative contralateral breast cancers was higher in the tamoxifen group than in the control group. There was no difference, however, between the two groups in recurrence-free survival time from the diagnosis of the contralateral cancer.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1886158 TI - Physical activity and risk of developing colorectal cancer among college alumni. AB - The assessment of physical activity at a single time to evaluate its association with cancer may be limited, since such a measure may not adequately reflect activity over the long term. To overcome this limitation, we studied 17,148 Harvard alumni aged 30-79 years who were followed prospectively for the occurrence of colon cancer (n = 225) and rectal cancer (n = 44) from 1965 through 1988. Physical activity, based on self-reported stair climbing, walking, and sports play, was assessed in either 1962 or 1966 (1962/1966) and again in 1977. The increased activity evaluated using either assessment (1962/1966 or 1977) taken alone was not associated with risk of colon cancer. However, alumni who were highly active (energy expenditure of greater than 2500 kilocalories/wk) at both assessments had half the risk of developing colon cancer relative to those who were inactive (less than 1000 kilocalories/wk) at both assessments (age adjusted rate ratio = 0.50; 90% confidence interval = 0.27-0.93), whereas those who were moderately active (1000-2500 kilocalories/wk) at both assessments had an age-adjusted rate ratio of 0.52 (90% confidence interval = 0.28-0.94). We conclude that either consistently higher levels of activity are necessary to protect against colon cancer or combining two assessments increased the precision of physical activity measurement. We found no evidence that increased physical activity protected against rectal cancer. PMID- 1886159 TI - Increased therapeutic index of antineoplastic drugs in combination with intracellular histamine antagonists. AB - L-Histidinol, a protein synthesis inhibitor and structural analogue of L histidine, has been demonstrated in chemotherapy-treated mice to be cytoprotective to normal stem cells but to enhance cytotoxicity to tumor cells. N,N-Diethyl-2-[4-(phenylmethyl) phenoxy]ethanamine.HCl (DPPE) is an antagonist of recently described microsomal and nuclear intracellular histamine receptors implicated in the mediation of proliferation and modulation of prostaglandin synthesis. DPPE is cytotoxic to tumor cells in vitro and cytoprotective to the gut in vivo. Noting the similar pharmacologic profiles for histidinol and DPPE and the structural resemblance between histidinol and histamine, we tested 1) whether binding to intracellular histamine receptors may be important to the action of histidinol, 2) whether there exists a differential effect of DPPE and histidinol on proliferating normal and transformed or malignant cells, and 3) whether DPPE, like histidinol, protects host cells from the effects of chemotherapy while augmenting tumor cell kill in vivo. It was observed that histidinol does compete at intracellular histamine receptors in isolated microsomes and nuclei, but with significantly lower affinity than DPPE. Nevertheless, for each agent, potency at intracellular histamine receptors correlates with potency to inhibit DNA and protein synthesis, without cytotoxicity, in normal mitogen-stimulated murine lymphocytes and to kill transformed mouse lymphocytes or MCF-7 human breast cancer cells. As demonstrated previously for histidinol (1-2 g/kg), DPPE (4 mg/kg) protected murine bone marrow progenitors from doxorubicin or fluorouracil, while doses of 4-50 mg/kg significantly enhanced the antitumor activity of doxorubicin and daunorubicin in murine models of early cancer. One postulate to explain the effects of intracellular histamine receptor ligands is that intracellular histamine mediates DNA and protein synthesis, possibly through a downward modulation of growth inhibitory prostaglandin levels. Antagonism of the intracellular action of histamine at intracellular histamine receptors by DPPE or histidinol may result in differential perturbations of growth/eicosanoid metabolism in normal and malignant cells, thus forming the basis of a new approach to chemotherapy. PMID- 1886160 TI - Nested case-control study of lung cancer in the meat industry. PMID- 1886161 TI - Routine screening for cancer of the prostate. PMID- 1886162 TI - Replication. PMID- 1886163 TI - Oligodendroglial cell death induced by oxygen radicals and its protection by catalase. AB - The cytotoxic effects of oxygen radicals have been studied in enriched population of mature bovine oligodendrocytes in culture. Oxygen radicals were generated enzymatically by glucose and glucose oxidase, and hypoxanthine and xanthine oxidase combinations. Cytotoxicity was assessed by trypan blue exclusion and percentage lactate dehydrogenase release into the culture media. Incubation of bovine oligodendrocytes with these oxygen radical-generating systems for 4 hr resulted in significant cell death, especially in the glucose oxidase system. The oligodendrocytes were completely protected by catalase from the cytotoxic effects of both oxygen radical generating systems. However, superoxide dismutase, dimethylsulfoxide and antioxidants such as vitamin E and glutathione did not protect oligodendrocytes from the oxidant-mediated cytotoxicity. It appears that hydrogen peroxide produced in these oxygen radical-generating systems gives rise to toxic radicals that induce the cell death of bovine oligodendrocytes in culture. PMID- 1886164 TI - Selective extraction, solubilization, and reversed-phase high-performance liquid chromatography separation of the main proteins from myelin using tetrahydrofuran/water mixtures. AB - The number of solvents capable of dissolving myelin and proteolipid protein (PLP) and of being used as a mobile phase for the separation of myelin proteins by reversed-phase high-performance liquid chromatography (RP-HPLC) is very limited. In a thorough study, we found that aqueous tetrahydrofuran (THF) fulfilled such a requirement. The maximal amount of protein extracted corresponded to a THF/water ratio of 4:1 v/v and a polarity index of 5.16. This mixture dissolved a purified PLP preparation completely, 60% of proteins from fresh myelin, and 20% of white matter total proteins. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) of those extracts, followed by densitometric analysis, showed that the amount and type of proteins dissolved depended on the polarity (i.e., the content of water) of the solvent mixture used. This selective effect was greater for basic protein in myelin preparations. Crude extracts highly enriched in basic protein can be prepared. In addition, the solvent system THF/water proved to be very useful as a mobile phase in RP-HPLC for separating myelin proteins. Using a C3 column and a linear gradient from 30% to 100% THF in water, both containing 0.1% trifluoroacetic acid (TFA), we separated completely the three main protein fractions of central nervous system (CNS) myelin in a short period of time. The high solubility power of THF/water mixtures prolonged greatly the life of the column. PMID- 1886165 TI - Characterization of ramified microglia in tissue culture: pinocytosis and motility. AB - Functional properties of ramified microglia were investigated in primary cultures of rat cerebral cortical cells. These microglia could be readily identified in both fixed and living cultures through previously established features. Based on their destruction by 5 mM L-leucine methyl ester, a high level of intrinsic endocytotic activity was established. When cultures were incubated with fluorescent latex beads to assess phagocytosis, little or no such activity was exhibited by ramified cells. However, when cultures were incubated with dyes or other soluble tracer compounds, these cells always exhibited labeling. This labeling was selective for ramified microglia in the cultures and was demonstrated using a variety of compounds, including trypan blue, lucifer yellow, horseradish peroxidase (HRP), and India ink. Intracellular label could be observed in vesicular structures; this localization corresponded to an active cellular process. Also, cellular labeling was inhibited by the presence of colchicine. These features supported the inference that the labeling was attributable to pinocytosis, and this process appeared to account for the vast majority of endocytotic activity in the ramified microglia. Possible physiological significance of this pinocytotic activity was indicated by the accumulation of various neurotransmitters/modulators: gamma-aminobutyric acid and vasoactive intestinal polypeptide (VIP). Ramified cells in these cultures have been previously noted to exhibit a constant and rapid pattern of motility, which was consistently observed here through time-lapse video recording; pinocytosis and rapid motility were shown to concur in individual cells. Based on their high intrinsic pinocytotic activity and pattern of cellular motility, the ramified microglia specifically are suggested to serve a constitutive function of fluid cleansing within the interstitial spaces of brain tissue. PMID- 1886166 TI - Non-competitive antagonists of N-methyl-D-aspartate prevent spontaneous neuronal death in primary cultures of embryonic rat cortex. AB - Primary cultures of embryonic rat cerebral cortex were treated after 17 days in vitro for 10 min with a single dose of the non-competitive antagonists of N methyl-D-aspartate (NMDA) receptor MK 801, TCP, and GK 11. They were then maintained in vitro for 31, 59, or 73 days, and then processed for the immunocytochemical detection of neuron-specific enolase (NSE). Immunoreactive cells were counted in treated and control cultures, and it was found that, except at 31 days, treated cultures contained far more NSE immunoreactive cells than controls. Moreover, this effect was dose-dependent, since with both TCP and GK 11 neuron survival was significantly higher with, respectively, 20 microM and 5 microM than with the lowest concentration of 2.5 microM. We tentatively conclude that spontaneous neuron death occurring in primary cultures in vitro is at least partly related to the NMDA-associated Ca++ channel, since the common property of the molecules we used is to block this channel. The relevance of this mechanism of cell death in vitro to neuronal death in vivo is discussed. PMID- 1886167 TI - Population-specific modulation of 5-HT expression in cultures of embryonic rat rhombencephalon. AB - This study aimed at analyzing the regulation of in vitro serotonin expression by neurons taken from different regions of the embryonic rat rhombencephalon. We studied the influence of co-culture with alarplate tissue using immunocytochemical and biochemical methods. Computer-assisted densitometry was used to estimate the co-culture effects on the serotonin content of the cell bodies. The more dynamic aspects of serotonin expression, such as synthesis and release, were studied by measuring (3H)serotonin newly synthesized from (3H)tryptophan. The density of the immunostaining was significantly decreased in B1,B2 cells by co-culture with both caudal and rostral alar-plate tissue. For B4 B9 cells, only co-culture with rostral alar-plate tissue produced a significant decrease. The de novo synthesis of serotonin was significantly decreased in B1,B2 neurons co-cultured with caudal alar-plate tissue only. Once again, the B4-B9 cells proved to be less influenced by the experimental conditions, as co-culture with both types of alar-plate tissue produced no significant effect. We concluded that the in vitro expression of serotonin can be modulated by environmental factors, but the relative influence of these factors is very different in rostral versus caudal serotonin expressing cell populations. PMID- 1886168 TI - In vitro changes in the fine structure and protein composition of light myelin fractions isolated from guinea pig brain. AB - To find out if in vitro maintenance produces changes in the electron microscopic appearance, protein composition and phosphorylation properties of guinea pig CNS myelin fractions, we incubated them for 10 min, 4 hr, 24 hr, and 48 hr in phosphate-buffered saline (pH 7.4) or in 20 mM Hepes, 2 mM EDTA, 0.5 mM EGTA, 0.5 mM dithiothreitol, and 20 mM NaCl at 4 and 30 degree C. Aliquots were processed for electron microscopic study, were analyzed for protein content by gel electrophoresis, and were assayed for endogenous protein phosphorylation. Before incubation, electron micrographs of fractions contained two types of multilamellar whorls with the periodicity of CNS myelin sheaths. The first type of whorl was separated from nearby whorls; the other type had surface lamellae that were connected to other multilayered membrane fragments. After incubation at 4 degree C for 24 hr, the number of both types of multilamellar whorls in micrographs had increased approximately 3- to 4- fold. Counts per unit area showed that the observed increase was both time- and temperature-dependent. In aliquots studied by gel electrophoresis, only minor degradation of myelin proteins was observed. The endogenous protein phosphorylation properties of the myelin fragments also remained functional, suggesting that the activities of protein phosphotransferases were not altered. We conclude that the incubation conditions described here favor interactions of proteins and lipids that lead to the formation of multilayered aggregates of CNS myelin membranes. PMID- 1886169 TI - The neurotrophic factor, n-hexacosanol, reduces the neuronal damage induced by the neurotoxin, kainic acid. AB - The long-chain fatty alcohol, n-hexacosanol, has been shown to possess neurotrophic properties in vitro on rat CNS cultures (Borg et al., 1987) and to promote the survival of septal cholinergic neurons after experimental axotomy (Borg et al., 1990). Long-chain alcohols have also been shown to be synthesized and metabolised by rat brain during development (Bishop and Hayra, 1981; Natarajan et al., 1984). The present study was undertaken in order to find out if a nonproteic neurotrophic factor like n-hexacosanol may be able to reduce the neuronal damages induced by the excitatory amino acid, kainic acid. When administered chronically by intraperitineal injection, hexacosanol (1 mg/kg) protected the pyramidal neurons of the hippocampus from the neurotoxic degeneration induced by an intracerebroventricular infusion of kainic acid in rats; the extent of the damage was limited to a small part of the CA3 region. Morphometric analysis showed that 72% of the neurons that would have died following kainic acid injection were spared by hexacosanol. Moreover the increased locomotor activity induced by the neurotoxin was also inhibited by hexacosanol and the behavioral effect was statistically correlated to the extent of neuronal loss. The present study suggests a possible role for nonproteic neurotrophic compounds against neurotoxic damages on central neurons. Moreover the peripheral administration of hexacosanol may lead to a significant breakthrough in the treatment of exicotoxin-related human diseases. PMID- 1886170 TI - Xenopus oocytes as immunological vectors to produce monoclonal antibodies to rat brain antigens. AB - A novel approach was developed to raise a panel of monoclonal antibodies (mAb) against brain antigens using Xenopus oocytes as immunological vectors. Xenopus oocytes were injected to express proteins encoded by brain-derived mRNA extracted from rat cerebral cortex. A crude membrane preparation from mRNA-injected oocytes was then used to immunize mice previously rendered immunotolerant to native oocyte membranes. mAb reacting with cryostat cut sections from rat brain were selected and further characterized by immunohistological and immunobiochemical techniques. Several mAb recognized brain specific antigens, including some that were cell type specific and others that revealed a regional binding pattern. A particular group of antibodies recognized an epitope localized exclusively to the cerebellar pinceau terminals. Although some of the hybridomas found in this panel may be products of natural autoreactive lymphocytes, the presence of a specific immune response to mRNA expression products is discussed. These results indicate that mRNA injected oocytes are useful tools to raise mAb to study the molecular diversity of the nervous system. PMID- 1886171 TI - Age-dependent decrease of process formation by cultured oligodendrocytes is augmented by protein kinase C stimulation. AB - The proportion of cultured rat oligodendrocytes (OL) that extended processes of over three soma diameter in length is dependent on the age of the animals from which the brains were derived; up to 70% of neonatal OL attained this criterion within 3 days, and this proportion progressively decreased with advancing ages of the animals (1, 3, and 6 months). The lower extent of process formation from older rat OL could be augmented, and indeed to equal neonatal levels, by treatment of cells with phorbol esters that stimulate protein kinase C: 4 beta phorbol-12,13-dibutyrate (PDB) and phorbol-12-myristate-13-acetate (PMA). Enhancement of process formation by PDB and PMA was also observed for cultured adult human and bovine OL. For adult OL from all three species, a phorbol ester that binds but that does not activate protein kinase C, 4 alpha-phorbol-12,13 didecanoate, did not result in enhancement of process formation. Selectively to biologically active phorbol esters was shown by the inability of a wide range of growth factors to promote process extension. Immunohistochemical analyses indicate that the type III isozyme of protein kinase C predominates in cultured OL; the apparent intensity of immunoreactive PKC was not different between controls or cultures treated for 12 days with PDB, suggesting that the persistent presence of PDB might not have down-regulated the enzyme, in contrast to other cell types. We propose that stimulation of protein kinase C is critical to the triggering of process formation by cultured OL in vitro. PMID- 1886172 TI - Plasma biochemistry values of young beagle dogs. AB - Plasma components of 6 to 12-month-old beagles were examined using a Technicon auto-analyzer. Age-related changes were noted for 8 of the 21 components: the levels of total protein (T. Pro) and iron (Fe) gradually increased while those of alkaline phosphatase (ALP), creatine phosphokinase (CPK) and inorganic phosphorus (Pi) persistently decreased in both sexes. Triglyceride (Trigly) in female dogs, glutamic-pyruvic transaminase (GPT) and urea nitrogen (Urea-N) in male dogs tended to increase. The following thirteen components showed no significant variation during the period of observation: glucose (Glu), lactic dehydrogenase (LDH), albumin (Alb), creatinine (Crea), glutamic-oxaloacetic transaminase (GOT), leucine aminopeptidase (LAP), total bilirubin (T. Bil), amylase (Amy), total cholesterol (T. Chol), sodium (Na), potassium (K), chloride (Cl) and calcium (Ca). Our results generally agree with the reported findings on beagles from various institutions. PMID- 1886173 TI - Automatic monitoring system for the measurement of body weight, food and water consumption and spontaneous activity of a mouse. AB - The simultaneous recording system for body weight, food and water consumption and behavior (spontaneous motor activity and drinking and feeding behavior) of a mouse was developed. The body weight and food consumption were measured by force transducers. Food and water consumption and drinking and feeding behavior were measured by an infrared luminous diode and a phototransistor. Spontaneous motor activity was measured by photosensors. The system control and data acquisition were performed by using a personal computer. Every parameter could be monitored with a desired time interval. All the data collected by this system revealed apparent circadian rhythm. In conclusion, this system would be a powerful tool for pharmacological and/or toxicological research. PMID- 1886174 TI - Intravenous self-administration of an enkephalin analog, EK-399, by rats. AB - The novel enkephalin analog Tyr-D-Met (O)-Gly-EtPhe-NHNHCOCH3 . AcOH (EK-399) was examined for psychic dependence potential by a self-administration test in rats. Five groups of experimentally naive rats were given an intravenous dose of EK-399 (0.032, 0.064 or 0.125 mg/kg), morphine HCl (0.5 mg/kg) or cocaine HCl (0.5 mg/kg) via a cannula implanted in the jugular vein when they pressed a lever. No animals initiated self-administration of EK-399 in the first 3 or 4 weeks of the experimental period. In contrast, almost all of the animals receiving morphine or cocaine initiated a high rate of self-administration within 1 or 2 weeks. However, when the doses of EK-399 were subsequently decreased, 4 of the 10 animals increased their rate of self-administration slightly. Furthermore, an increase in the rate of EK-399 self-administration was observed in 1 of 4 rats made physically dependent on EK-399. These results suggest that EK-399 has a very weak reinforcing effect on drug-taking behavior, which is slightly enhanced by the development of physical dependence on the compound, and it may possess a low psychic dependence potential. PMID- 1886175 TI - Health groups pin antitobacco hopes on turn-of-century high school class. PMID- 1886176 TI - Immune boosters disappoint AIDS researchers. PMID- 1886177 TI - Medical roads lead to new hospital in Rome. PMID- 1886178 TI - From the Centers for Disease Control. Opportunistic non-Hodgkin's lymphomas among severely immunocompromised HIV-infected patients surviving for prolonged periods on antiretroviral therapy--United States. PMID- 1886179 TI - From the Centers for Disease Control. St Louis encephalitis outbreak--Arkansas, 1991. PMID- 1886180 TI - A piece of my mind. Morning distort. PMID- 1886181 TI - Assessing prior history of sexually transmitted disease. PMID- 1886182 TI - The incidence of HBV infection and syringe exchange programs. PMID- 1886183 TI - The future of medical care. PMID- 1886184 TI - Detection of iron deficiency anemia. PMID- 1886185 TI - Trigeminal neuralgia relieved by optical anesthesia. PMID- 1886186 TI - Teaching intubation skills using newly deceased infants. PMID- 1886187 TI - Loma Linda MD/pilots should train at USC. PMID- 1886188 TI - Human immunodeficiency virus infection in urban Rwanda. Demographic and behavioral correlates in a representative sample of childbearing women. AB - OBJECTIVE: --To determine behavioral and demographic risk factors for human immunodeficiency virus (HIV) infection in central Africa. DESIGN: --Cross sectional survey. SETTING: --Kigali, Rwanda. PARTICIPANTS: --A representative sample of 1458 childbearing women aged 19 to 37 years who were recruited from outpatient prenatal and pediatric clinics at the only community hospital in the city. MAIN OUTCOME MEASURE: --Antibodies to HIV assessed by enzyme immunoassay and confirmed by Western blot or indirect immunofluorescence. RESULTS: --The HIV seroprevalence was 32% overall. Infection rates were higher in women who were single, in those in steady relationships that began after 1981, and in the 33% of women reporting more than one lifetime sexual partner. Women in legal marriages or monogamous partnerships had lower rates of infection, but even low-risk women had prevalences on the order of 20%. History of venereal disease in the past 5 years, although the strongest risk factor in a multiple logistic analysis (odds ratio, 2.7; 95% confidence interval, 2.0 to 3.7), was reported by only 30% of those infected. Having a male sexual partner who drank alcohol or who had higher income were significant risk factors for HIV infection in the multivariate analysis, but use of oral contraceptives and having an uncircumcised partner were not. CONCLUSIONS: --The epidemic of the acquired immunodeficiency syndrome in Rwanda has spread beyond high-risk groups to the general population of women without known risk factors. For most of these women, a steady male partner is the source of their HIV risk and therefore a vital target for intervention efforts. PMID- 1886189 TI - Female-to-male transmission of human immunodeficiency virus. AB - OBJECTIVE: --To examine rates of heterosexual transmission of human immunodeficiency virus (HIV) and associated risk factors and to determine the relative efficiency of female-to-male and male-to-female transmission. DESIGN: - Survey of infected individuals and their heterosexual partners recruited since 1985. SETTING: --Participants were recruited from various HIV counseling and testing sites throughout California but were generally interviewed and tested in their homes. PARTICIPANTS: --Data from 379 couples at entry to the study are reported: 72 male partners of infected women and 307 female partners of infected men. The infected index case had a well-established source of risk; couples were eliminated if the direction of transmission could not be established. The majority of couples were monogamous since 1978, white, and in their 30s. Most partners did not know their serostatus at entry into the study. MAIN OUTCOME MEASURE: --HIV serostatus in the exposed sexual partner. RESULTS: --We observed one probable instance (1%) of female-to-male transmission compared with 20% transmission rates in the female partners of infected men. All couples were sampled in the same way. Male index cases were more likely to be symptomatic than female index cases. CONCLUSION: --The odds of male-to-female transmission were significantly greater than female-to-male transmission. The one case of female-to male transmission was unique in that the couple reported numerous unprotected sexual contacts and noted several instances of vaginal and penile bleeding during intercourse. PMID- 1886190 TI - Mechanisms of glove tears and sharp injuries among surgical personnel. AB - OBJECTIVE: --The development of strategies to prevent exposure to blood for operating room personnel has been hampered by a lack of knowledge about the specific mechanisms of exposure. The purpose of this study was to classify the mechanisms of glove tears and sharp injuries in the operating room. DESIGN: - During a 3-month period, a nurse interviewed operating room personnel immediately after a glove tear or sharp injury had occurred. SETTING: --Yale-New Haven (Conn) Hospital is a tertiary care teaching hospital. RESULTS: --There were 249 glove tears and 70 sharp injuries. Visible skin contact with the patient's blood occurred in 156 glove tears (63%). The mechanism causing the tear could be identified in only 81 (33%). For 230 glove tears (92%), personnel were wearing single gloves. Of 70 sharp injuries, 47 (67%) were caused by needles and usually occurred during suturing. The following three mechanisms accounted for 40 sharp injuries (57%): (1) hands injured while stationary and holding an instrument, 11 (16%)-a position of risk not previously identified; (2) hands injured while retracting tissue, 12 (17%); and (3) injuries caused by sharp instruments not being used, 17 (24%). Instrument passage caused only four sharp injuries (6%). CONCLUSIONS: --The majority of glove tears have an unknown mechanism, and alteration in the manufacture or number of gloves worn may be helpful in reducing cutaneous blood exposures. The identification of specific mechanisms of sharp injuries should lead to effective strategies to prevent exposure to the human immunodeficiency virus and other blood-borne pathogens in the operating room. PMID- 1886191 TI - Cardiac toxicity 4 to 20 years after completing anthracycline therapy. AB - OBJECTIVE: --To assess the cardiac status of long-term survivors of pediatric malignancies who received chemotherapy, including anthracyclines. DESIGN AND METHOD: -Patients were evaluated by echocardiogram from 4 to 20 years (median, 7 years) after completion of anthracyclines, with prospective and retrospective analysis. PATIENTS: --The consecutive sample of 201 patients had received a total anthracycline dose of 200 to 1275 mg/m2 (median, 450 mg/m2), and 51 patients had mediastinal radiotherapy. MAIN OUTCOME MEASURES: --The overall incidence and severity of abnormal systolic cardiac function were determined for the entire cohort. Risk factors of total anthracycline dose, mediastinal radiotherapy, age during treatment, and length of follow-up were examined. RESULTS: --Twenty-three percent (47/201) of the cohort had abnormal cardiac function on noninvasive testing at long-term follow-up. Correlation between total cumulative dose, length of follow-up, and mediastinal irradiation with incidence of abnormalities was significant. Fifty-six patients were followed up for 10 years or more (median, 12 years), with a median anthracycline dose of 495 mg/m2. Thirty-eight percent (21/56) of these patients, compared with 18% (26/145) of patients evaluated after less than 10 years, had abnormal findings. Sixty-three percent of patients followed up for 10 years or more after receiving 500 mg/m2 or more of anthracyclines had abnormal findings. Nine of 201 patients had late symptoms, including cardiac failure and dysrhythmia, and three patients died suddenly. Microscopic examination of the myocardium on biopsy and autopsy revealed fibrosis. CONCLUSION: --The 23% incidence of late cardiac abnormalities warrants continued evaluation of patients after anthracyclines to guide patient care and the design of future chemotherapeutic protocols. PMID- 1886193 TI - A critical evaluation of new agents for the treatment of sepsis. AB - OBJECTIVE - To evaluate new treatments directed against endotoxin, tumor necrosis factor alpha, and interleukin 1 for use in sepsis and related disorders (sepsis syndrome and septic shock). DATA SOURCES - Investigations of these treatments in animal models, healthy human volunteers, and patients with sepsis and related disorders. STUDY SELECTION - Particular attention was paid to studies of patients with sepsis and related disorders, especially randomized, double-blind, controlled trials. DATA EXTRACTION - Animal studies and investigations with human volunteers were judged by how closely the experimental model replicated the clinical disorder (sepsis). Patient trials were assessed by sample size and design. Results of all studies were used to evaluate the likelihood that a given treatment would reduce mortality. DATA SYNTHESIS - Direct comparison of E5 and HA 1A antibody studies is difficult because of differences in their design, definitions of shock, and methods of subgroup analysis. However, both antibodies improve outcome in some subgroups: E5 benefits patients with gram-negative infection (bacteremic or focal) who do not have refractory shock, and HA-1A benefits those with gram-negative bacteremia (regardless of whether shock is present) but not those with focal gram-negative infection. Two agents that may be beneficial in gram-positive and gram-negative infection are monoclonal antibodies to tumor necrosis factor alpha and receptor antagonists to interleukin 1. Preliminary results with both are reviewed. CONCLUSIONS - All three types of treatment may improve outcome in sepsis. The best results will probably be obtained with combination therapy that interrupts multiple points of the inflammatory cascade underlying sepsis. PMID- 1886194 TI - The right road for medicine. Professionalism and the new American Medical Association. PMID- 1886195 TI - Heterosexual transmission of HIV. A view of the future. PMID- 1886192 TI - Estimating an individual's true cholesterol level and response to intervention. AB - An individual's blood cholesterol measurement may differ from the true level because of short-term biological and technical measurement variability. Using data on the within-individual and population variance of serum cholesterol, we addressed the following clinical concerns: Given a cholesterol measurement, what is the individual's likely true level? The confidence interval for the true level is wide and asymmetrical around extreme measurements because of regression to the mean. Of particular concern is the misclassification of people with a screening measurement below 5.2 mmol/L who may be advised that their cholesterol level is "desirable" when their true level warrants further action To what extent does blood cholesterol change in response to an intervention? In general, confidence intervals are too wide to allow decision making and patient feedback about an individual's cholesterol response to a dietary intervention, even with multiple measurements. If no change is observed in an individual's cholesterol value based on three measurements before and three after dietary intervention, the 80% confidence interval ranges from a true increase of 4% to a true decrease of 9%. PMID- 1886197 TI - [Regional meetings of the Japanese Circulation Society. 1987-1988. Abstracts]. PMID- 1886196 TI - Measuring and knowing. The trouble with cholesterol and decision making. PMID- 1886199 TI - [Enhancement of susceptibility of sulbactam/cefoperazone-treated bacteria to phagocytes]. AB - Effects of sulbactam/cefoperazone (SBT/CPZ) on the host-parasite relationship were studied using an established mouse macrophage cell line. Since SBT inactivates some types of beta-lactamase strongly, a combination of SBT with CPZ shows marked antibacterial activities against the bacteria producing beta lactamases. In addition, sub-MIC levels of SBT/CPZ made Escherichia coli more susceptible to bactericidal activity of macrophage. This study provides evidence that SBT/CPZ works in partnership with host defense mechanism against bacterial infections in clinical situations. PMID- 1886200 TI - [Cefepime in the treatment of patients with surgical infections]. AB - Between March 1988 and June 1990, we gave cefepime to 5 subjects after surgery and studied the pharmacokinetics of the drug. In the same period, we treated 23 patients with surgical infections with the same drug and evaluated its clinical efficacy. In the pharmacokinetic study, 1 g was given intravenously to each individual over a 30 minutes period. The peak levels in the plasma, 59.9-118 micrograms/ml, were obtained at around the end of this time. The peak levels in the bile, 7.1-28.2 micrograms/ml, were reached at 1-5 hours after administration, depending on the patient. At hours 5 and 6, the range of plasma concentration was 3.7-12.3 micrograms/ml. In the 22 patients with surgical infections, clinical efficacy of the drug was excellent in 12, good in 5, fair in 1, and poor in 4, with an overall efficacy rate of 77%. The bacteriological response was evaluated in the 16 patients for whom the species of the probable causative organisms were identified. Those bacteria were eradicated in 10 patients, decreased in 3, and were persisted in 3, with an eradication rate of 63%. Against 5 strains of Escherichia coli isolated, the highest MIC was 0.05 micrograms/ml, and against 2 strains of Pseudomonas aeruginosa isolated, the MIC was 1.56 micrograms/ml, so this drug should be highly effective toward these species. Three strains of Staphylococcus aureus were isolated, one of which was resistant to methicillin. It was not eradicated. PMID- 1886198 TI - [New antimicrobial agent series XL: arbekacin]. PMID- 1886203 TI - [Acute renal failure--definition, classification and clinical statistics]. PMID- 1886201 TI - [Laboratory and clinical studies on cefpirome in pediatrics]. AB - Cefpirome (HR 810, CPR), a new cephem antibiotic, was investigated for its experimental and clinical studies in pediatrics. The results obtained are summarized as follows. 1. Plasma and urinary levels of CPR were determined in 2 children (age 5 and 7 years) after the one shot intravenous injection of the drug at 20 mg/kg. Average plasma levels of the drug were 44.7 micrograms/ml, 28.5 micrograms/ml, 10.5 micrograms/ml, 4.6 micrograms/ml and 1.5 micrograms/ml at 1/2 hour, 1 hour, 2 hours, 4 hours and 6 hours, respectively, and the average half life was 1.57 hours. Average urinary levels of the drug were 1,785 micrograms/ml, 545 micrograms/ml and 198 micrograms/ml at 0-2 hours, 2-4 hours, 4-6 hours, respectively and the average urinary elimination rate was 52.0%. The results were nearly equivalent to those in adults except for urinary elimination rate which tended to be slightly lower than that in adults. 2. Cerebrospinal fluid levels in 3 cases of purulent meningitis treated with CPR were investigated. Cerebrospinal fluid levels in a case of Neisseria meningitidis were 11.5-23.1 micrograms/ml at 1 hour and 0.94 microgram/ml at 5 hours after intravenous injection of 44.4 mg/kg, 4 times a day. Cerebrospinal fluid levels in a case of Streptococcus pneumoniae were 1.01-4.23 micrograms/ml at 1 hour after intravenous injection of 49.0 mg/kg, 6 times a day, and in the other case with Streptococcus pneumoniae, the levels were 16.8-37.1 micrograms/ml at 1 hour, 11.3 and 3.60 micrograms/ml at 3 and 4 hours after intravenous injection 52.2 mg/kg, 6 times a day. These results are not inferior to those with cefotaxime or ceftriaxone. These levels appear to be higher than MIC90 values against Escherichia coli, Streptococcus agalactiae, S. pneumoniae or Haemophilus influenzae which are the major pathogens of these diseases. 3. CPR was given to 62 patients and clinical efficacy, bacteriological response and adverse reactions were evaluated. Evaluated cases for clinical efficacy included 3 cases of purulent meningitis, 1 case of acute purulent otitis media, 2 cases of acute purulent tonsillitis, 1 case of acute bronchitis, 49 cases of acute pneumoniae, 1 case of scarlet fever, 1 case of acute osteomyelitis, 1 case of acute enterocolitis, and 2 cases of acute UTI, totalling 61 cases. Clinical efficacies were excellent in 38 cases, good in 22 cases and fair in 1 case with an efficacy rete of 98.4% (excellent + good).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1886202 TI - [Susceptibilities of bacteria isolated from patients with respiratory infectious diseases to antibiotics (1988)]. AB - Isolated bacteria from respiratory infectious diseases were collected in cooperation with institutions located throughout Japan, since 1981, and Ikemoto et al. have been examining sensitivities of the isolates to various antibacterial agents and antibiotics, relationships between the isolates and the backgrounds of the patients and so forth each year. We report here the research results for the year 1988. In 18 institutions around the entire Japan from October 1988 to September 1989, 554 strains of bacteria were isolated mainly from the sputa of 439 patients with respiratory infectious diseases and assumed to be the etiologic bacteria. MICs of various antibacterial agents and antibiotics against 68 strains of Staphylococcus aureus, 102 strains of Streptococcus pneumoniae, 120 strains of Haemophilus influenzae, 86 strains of Pseudomonas aeruginosa, 65 strains of Branhamella catarrhalis, 18 strains of Klebsiella pneumoniae and so forth, were determined, and the drug sensitivities of these strains were examined except for the strains which died during transportation. The drug sensitivities of the main strains were almost the same as those determined last year for each drug. However, S. aureus strains for which MICs of methicillin were higher than 12.5 micrograms/ml (methicillin-resistant S. aureus) accounted for 38.2%, and the frequency of drug resistant bacteria increased over last year's 18.2%. Also, we examined changes in the backgrounds of patients, the infectious diseases, and the etiologic bacteria and so forth. As to patient backgrounds, there were many infectious diseases found in a high age bracket, and the patients over age 60 accounted for 57.2% of the diseases. In the distribution by disease, bacterial pneumonia and chronic bronchitis accounted for greatest numbers of cases 32.1% and 31.4%, respectively, followed by bronchiectasis and bronchial asthma. As for frequencies of etiologic bacteria by disease, S. aureus (22.5%) and S. pneumoniae (15.4%) in pneumonia, S. pneumoniae (25.7%) and H. influenzae (24.1%) in chronic bronchitis, H. influenzae (32.5%) and P. aeruginosa (23.8%) in bronchiectasis, and H. influenzae (31.4%), S. pneumoniae and B. catarrhalis (20.0%) in bronchial asthma were the most frequent. Regarding effects of administration of antibiotics and isolates obtained on each day after infection, those bacteria which were isolated before antibiotic administration and which decreased after administration included S. pneumoniae, H. influenzae, and B. catarrhalis. Frequencies of S. aureus and P. aeruginosa, however, increased after antibiotic administration. Also, when dosing continued for more than 15 days, the frequency of P. aeruginosa increased rapidly. PMID- 1886204 TI - [Acute renal failure]. PMID- 1886205 TI - [Acute renal failure--signs and symptoms]. PMID- 1886206 TI - [Acute renal failure--its basic histopathology]. PMID- 1886207 TI - [Experimental models of acute renal failure]. PMID- 1886208 TI - [Hemodynamics in acute renal failure]. PMID- 1886209 TI - [Urine concentrating and diluting ability in acute renal failure]. PMID- 1886211 TI - [Electrolyte and acid-base disorders in ARF]. PMID- 1886210 TI - [Tubuloglomerular feedback]. PMID- 1886212 TI - [Acute renal failure in heart failure]. PMID- 1886213 TI - [Acute glomerulonephritis, nephrotic syndrome]. PMID- 1886214 TI - [Acute renal failure in patients with diseases of the liver and biliary system]. PMID- 1886215 TI - [Hematological disorders]. PMID- 1886216 TI - [Acute renal failure in various diseases--solid tumor]. PMID- 1886217 TI - [Rhabdomyolysis]. PMID- 1886218 TI - [Acute renal failure induced by antimicrobial and antineoplastic agents]. PMID- 1886219 TI - [Acute renal failure induced by non-steroidal antiinflammatory drugs and antirheumatics (gold and D-penicillamine]. PMID- 1886220 TI - [Acute renal failure induced by non-drug chemical agents and contrast media]. PMID- 1886221 TI - [Bites, stings and food poisoning]. PMID- 1886222 TI - [Acute renal failure caused by mamushi bite]. PMID- 1886223 TI - [Acute renal failure in surgical and emergency patients]. PMID- 1886224 TI - [Obstetric acute renal failure]. PMID- 1886225 TI - [Acute renal failure associated with urological diseases]. PMID- 1886226 TI - [Acute renal failure in childhood]. PMID- 1886227 TI - [Acute renal failure in the elderly]. PMID- 1886228 TI - [Disseminated intravascular coagulation, hemolytic uremic syndrome, and acute renal failure]. PMID- 1886229 TI - [Goodpasture's syndrome and pseudo-Goodpasture's syndrome]. PMID- 1886230 TI - [Acute renal cortical necrosis and renal papillary necrosis]. PMID- 1886231 TI - [Shock and acute renal failure]. PMID- 1886232 TI - [Acute renal failure in patients with multiple organ failure]. PMID- 1886233 TI - [Acute deterioration in chronic renal failure]. PMID- 1886234 TI - [Prognosis of acute renal failure]. PMID- 1886235 TI - [The structures and functions of enterotoxins from Escherichia coli]. PMID- 1886236 TI - [Fulminant hepatitis B and mutant virus]. PMID- 1886237 TI - [Technological progress in visualization of functional aspects of brain]. PMID- 1886238 TI - [An introduction: diagnostic imaging and brain function]. PMID- 1886239 TI - [Clinical application of Xe-133 SPECT]. PMID- 1886240 TI - [Quantitative measurement of cerebral blood flow by 123I-IMP SPECT]. PMID- 1886241 TI - [Single-photon emission CT (SPECT) with 99mTc-ECD]. PMID- 1886242 TI - [Measurement of regional cerebral blood flow using H215O bolus-injection method]. PMID- 1886243 TI - [15O2 inhalation method: cerebral metabolic rate of oxygen (CMRO2)]. PMID- 1886244 TI - [Measurement of cerebral glucose metabolism using 11C-labeled glucose]. PMID- 1886246 TI - [Positron tracer, 11C-1-pyruvate: pyruvate metabolism]. PMID- 1886245 TI - [Amino acid metabolism in glioma patients studied with PET using 11C-methionine]. PMID- 1886247 TI - [Tomographic measurement of human cerebral glucose metabolism]. PMID- 1886248 TI - [Transport of phenylalanine in human brain by L-[2-18F]-fluorophenylalanine and PET]. PMID- 1886249 TI - [In vivo mapping of muscarinic acetylcholine receptors]. PMID- 1886250 TI - [Serotonin receptor]. PMID- 1886251 TI - [Measurement of serotonin uptake site in the human brain using PET]. PMID- 1886252 TI - [Mapping of histamine H1 receptors in human brain by positron emission tomography]. PMID- 1886253 TI - [Current and future radiopharmaceuticals for brain functional studies with PET and SPECT]. PMID- 1886254 TI - [Basic theory of MRA and development of imaging technique]. PMID- 1886255 TI - [MR angiography of intra- and extracranial vessels using gradient echo sequence; optimal pulse sequences and parameters]. PMID- 1886256 TI - [Three-dimensional MR angiography; its application for intracranial vascular lesions]. PMID- 1886257 TI - [Visualization of intracranial C.S.F. and blood flows with cine-MR imaging]. PMID- 1886258 TI - [Cine MR angiography--application to cerebrovascular disease]. PMID- 1886260 TI - [Localized spectroscopy and chemical shift imaging]. PMID- 1886259 TI - [Flow imaging of brain by means of DBI sequence]. PMID- 1886261 TI - [The development of clinical high tesla MRI/S system]. PMID- 1886263 TI - [Multinuclear MRS and CSI techniques for clinical applications]. PMID- 1886262 TI - [Problem of the localization software in clinical MRS]. PMID- 1886264 TI - [Dementia and human in vivo 31P-MRS]. PMID- 1886265 TI - [31P-MRS (brain tumors)]. PMID- 1886266 TI - [Study of cerebral infarction using 31P MRS]. PMID- 1886267 TI - [Applications of in vivo 13C NMR spectroscopy]. PMID- 1886268 TI - [Estimation of neuronal cell viability by 23Na magnetic resonance spectroscopy]. PMID- 1886269 TI - [Study of dementia, epilepsy and schizophrenia using P-CSI]. PMID- 1886270 TI - [31P chemical shift imaging of cerebral infarction, intracerebral hematoma and brain tumor]. PMID- 1886271 TI - [C-13 chemical shift imaging of the rat head in vivo]. PMID- 1886272 TI - [Metabolism of fluorohexoses in brain]. PMID- 1886273 TI - [Advances of magnetoencephalography--clinical application of a 37 channel biomagnetometer]. PMID- 1886274 TI - [Enzyme immunoassay for secretory immunoglobulin A on skin surface and in sweat]. AB - Recently secretory IgA (S-IgA) was found to be secreted from the eccrine gland. By using a sandwich enzyme immunoassay, we measured the concentration of S-IgA 1) in sweat (sweat S-IgA) and 2) in the extract buffer obtained by pipetting++ on the skin (skin surface S-IgA). Skin surface hydration and skin surface lipid were measured at the sites where the samples of skin surface S-IgA were collected. (These measurements were taken immediately after the buffer was pipetted). The quantity of both sweat S-IgA and skin surface S-IgA differed according to the sites where they were collected. Sites in order of decreasing sweat S-IgA level: face, chest, forearm. Sites in order of decreasing skin surface S-IgA level: face, chest, palm, forearm, sole. (Skin surface S-IgA levels on palm and forearm were approximately equal). Although the amount of skin surface S-IgA was not related to the skin surface hydration, there was a significant correlation between skin surface S-IgA and skin surface lipid. PMID- 1886275 TI - [Morphological changes in sebaceous glands with aging in human males]. AB - Using a computer stereographic analysis, the normal human forehead skin from 16 males of ages ranging from 7 to 77 years were investigated to known the morphological changes of the sebaceous glands with aging. The volume of sebaceous glands increased abruptly in teens, reaching maximum in the 20s; it was maintained at high levels even at middle ages and then began to decrease gradually in the 60s. The volume of sebaceous glands positively correlated with the number of the sebaceous cells but not with their sizes. Ultrastructually, in the large sebaceous glands, and peripheral cells were cuboidal, whereas they were flat in the small sebaceous glands. It is concluded that the sebaceous glands in males show no morphological change in relation to age between the 20s and 50s. PMID- 1886276 TI - [Normolipemic xanthoma developed on alopecia lesion on a SLE patient- histological study]. AB - A 30-year-old SLE patient developed a xanthoma on her alopecia lesion. Histological examination showed typical lupus changes including immunofluorescence stainings. In addition, there were numerous xanthoma cells existed through the dermis, interlobular spaces of subcutaneous fat tissue, perivascular areas of small blood vessels, and subendothelial spaces and inside of intraluminal thrombosis of subcutaneous small arteries. These xanthoma cells contained granular materials in their cytoplasm. Histochemically, these materials are diastase resistant P.A.S. (+), immunoglobulin (+), Sudan BB (+), Sudan III (+), Nile blue (pinkish red), and yellowish orange autofluorescence suggesting that they are lipofuscin or lipid peroxidation products. Further histological findings showed destruction of sebaceus glands and peri-glandular++ infiltration of lymphocytes and histiocytes. These histiocytes contained phagocytic neutral lipid droplets in their cytoplasm. Very small lipid peroxides were also seen on surface and/or cytoplasm of infiltrating lymphocytes existing not only peri lobular area but also intraluminal area of blood vessels. The marker profile of these infiltrating lymphocytes are B-cell predominant admixed with some CD8(+) T cells. These data suggest that the mechanism of developing xanthoma is initiated by immune-complex deposition on basal lamina of sebaceus glands, followed by destruction of sebaceus glands by lympho-histiocytic cells infiltration with some antigen presenting and/or effector cells, and finally xanthoma cells were developed by phagocytosis of lipid peroxides caused by macrophage-derived oxygen radicals. Interestingly, our data suggest that the lipid peroxides, which may act as photosensitizer, may leave the skin and may enter the small vessels carried by lymphocytes. Furthermore the xanthoma cells may also enter the circulation through the small arteries. PMID- 1886277 TI - [Delusions of parasitosis--report of 94 cases]. AB - The present article describes 94 patients (34 male and 60 female) with delusions of parasitosis, admitted to our dermatology clinic between 1978 and 1989. The female to male ratio was to one under the age of 45, and 1:2.1 over 45. The mean age of onset in males was 46.4 years, and in females, 52.8. In nine patients (6 male and 3 female), the delusions began shortly after their retirement, while in seven (1 male and 6 female) after separation from their families. The ratio of the number of patients living alone to that of patients living with their families was one to two, three times higher than that of the general population (1:6). About half of the patients had no skin lesions, while half the rest had excoriations. Three had eczematous lesions caused by the application of insecticides. In 58 patients, the creatures of delusion were mites. Most patients complained of some kind of cutaneous sensations of the skin, such as itching, tickling and prickling, while only two complained of auditory sensations. The color of creatures of delusion was black or white. Folie a deux was observed in 23 groups and affected both sexes. PMID- 1886278 TI - [Adult dermatomyositis with angiopathy and cecum perforation]. AB - This previously healthy 43-year-old man was admitted to our hospital with a history of rash, dysphagia and severe myalgia for two months. Physical examination showed prominent edema and erythema over the face and the chest, scattered ulcerations on the trunk, and muscle atrophy most prominent proximally. Serum levels of muscle enzymes were remarkably increased. Two weeks of oral prednisolone therapy (40 mg/day) was not effective, and betamethasone intravenous pulse therapy (3 x 1000 mg) was followed by slight clinical improvement. However, 12 days after pulse therapy, he complained abdominal pain on the right lower quadrant. The surgical findings included peritonitis due to single perforation of the cecum. After operation, cyclosporine therapy was added and over the next 14 month a considerable clinical improvement was noted. Prednisolone was reduced from 80 mg to 10 mg daily. Biopsy specimens from ulcerated+ skin and perforated cecum showed prominent vascular abnormalities: arterial and venous intimal hyperplasia, occlusion of vessels by fibrin thrombi, and lymphocytic infiltration which affected veins of all sizes. The evidence strongly suggests that both skin ulcers and cecum perforation were caused by vasculitis and occlusion of vessels, which often seen in childhood dermatomyositis. PMID- 1886279 TI - [Two cases of transient acantholytic dermatosis--with the analysis of 20 cases reported in Japan]. AB - Two cases of transient acantholytic dermatosis were reported. The first case was a 78-year-old male and showed pruritic papulovesicular lesions on the face, head, neck and back. Darier-like pattern was observed histologically. Oral administration of etretinate (40 mg/day) was effective. The second case was a 57 year-old male showed asymptomatic, herpetiform confluent vesiculo-papules on the right forearm. Darier-like pattern was dominantly observed with a focal spongiotic acantholysis histologically. Also 20 cases (10 males and 10 females) reported in Japan were collected and analyzed. PMID- 1886280 TI - [A case of benign cephalic histiocytosis]. AB - A 15-month-old girl had an asymptomatic eruption of yellowish-brown flat papules of 12 months' duration. Those papules were seen multiply on her face and in a small number on her neck and trunk. Skin biopsy showed a massive infiltrate of histiocytic cells in the upper and middle dermis. Electron microscopically, these cells had comma-shaped bodies in the cytoplasm, and formed desmosome-like junctions at the cell peripheries. A diagnosis of benign cephalic histiocytosis was made on the basis of these clinical, histological, and ultrastructural findings. To the best of our knowledge, this is the first report of benign cephalic histiocytosis in Japan. PMID- 1886281 TI - [Prognostic significance of scintigraphic silent myocardial ischemia detected by stress thallium scan in patients with recent myocardial infarction]. AB - To evaluate the prognostic significance of scintigraphic silent myocardial ischemia (SMI) detected by stress thallium scan in patients with myocardial infarction (MI), we performed a retrospective investigation on cardiac events (CE) during a two-year follow-up period in 149 patients with MI within three months of onset (34 +/- 19 days). SMI was defined as asymptomatic redistribution (RD) in the infarcted area. The patients were divided into three groups based on results of stress thallium scan as follows: 50 patients with neither chest pain nor RD (Group A), 46 patients with SMI (Group B) and 53 symptomatic patients (Group C). In comparison of the incidence of CE, which included cardiac death, recurrent MI, chronic heart failure, angina pectoris, PTCA, CABG and severe ventricular arrhythmia (lown grade greater than or equal to 3) during two-year follow-up, Group C had significantly higher incidence of PTCA and CABG than Group B (p less than 0.01), but there was no significant difference of other CE between groups B and C except PTCA and CABG. In addition, Groups B and C had a significantly higher incidence of CE than Group A in cardiac event-free curves, but there was no significant difference for Groups B and C. We conclude that patients with SMI are associated with unfavorable prognosis as symptomatic patients and that these patients should undergo careful follow-up. PMID- 1886282 TI - [Clinical evaluation of 123I-MIBG for assessment of the sympathetic nervous system in the heart (multi-center clinical trial)]. AB - Multi-center clinical trial of 123I-metaiodobenzylguanidine (123I-MIBG) was carried out to assess its utility as a scintigraphic imaging agent reflecting sympathetic neuronal function in cardiovascular field. Studies were performed on patients with heart diseases of three categories, myocardial infarction, angina pectoris and cardiomyopathy. Scintigraphic images, reflecting sympathetic neuronal function were obtained with 123I-MIBG from all of those categories of patients and the efficacy of the imaging was revealed in 781 (95.0%) out of 822 patients. In some patients abnormality was suggested in sympathetic neuronal function with 123I-MIBG imaging, in spite of normal findings with myocardial perfusion scintigraphy by 201TlCl. In all 981 patients studied with 123I-MIBG, there have been no severe adverse reactions, except complaints of burning on injection site of the agent or nausea, etc. from 4 patients. We conclude that 123I-MIBG imaging is one of the effective tools for diagnostic use reflecting topical sympathetic neuronal function in the heart, judging from its safety and efficacy. PMID- 1886283 TI - [Experimental study of per-rectal portal scintigraphy using 99mTc-EHIDA]. AB - We discovered that 99mTc-EHIDA commonly used for hepatobiliary scintigraphy could also be administered per-rectally, with adequate absorption and optimal visualization of the portal system. To evaluation its usefulness, we experimented on rabbits using the method. Portal scintigraphy with rectal administration of 99mTc-EHIDA, 123I-IMP and 99mTc-RBC were performed in normal rabbits and in extrahepatic portal shunt model rabbits. Images of the liver and thorax were obtained and shunt indices were calculated from the count values of liver and lung or heart. Then the shunt indices were compared with shunt rate derived from direct injection of 99mTc-MAA into inferior mesenteric vein. Correlation between shunt rate of 99mTc-MAA and shunt indices of 99mTc-RBC, 123I-IMP and 99mTc-EHIDA were 0.64, 0.75 and 0.78, respectively, with 99mTc-EHIDA having the most favourable results. We concluded that 99mTc-EHIDA per-rectal portal scintigraphy is a noninvasive, quantitative, inexpensive and simple method for evaluation of portal circulation system. Also, we think that this method would be applicable to human usage from our experience with normal volunteers. PMID- 1886284 TI - [Single photon emission computed tomography using 99mTc-hexamethylpropyleneamine oxime in patients with metastatic brain tumor or intracranial malignant lymphoma]. PMID- 1886285 TI - [Cerebral perfusion reserve SPECT imaging before and during acetazolamide test using consecutive 99mTc-HMPAO SPECT]. PMID- 1886286 TI - [Clinical evaluation of immunoradiometric assay for serum cardiac myosin light chain I]. PMID- 1886287 TI - Effects of MCI-727, a new antiulcer agent, on various gastric and duodenal lesions in experimental animals. AB - Effects of a new antiulcer drug, MCI-727, on gastric and duodenal lesions, gastric secretion and gastric motility were studied in comparison with cimetidine and teprenone. MCI-727 dose-dependently (3-100 mg/kg, p.o. or i.d.) inhibited the development of acute gastric or duodenal lesions such as pyrolus ligation-, water immersion stress-, indomethacin-, HCl-, HCl-ethanol-induced gastric lesions and cysteamine-induced duodenal lesions in rats and histamine-induced duodenal lesions in guinea pigs. These antiulcer effects exceeded those of cimetidine or teprenone. Repeated administration of MCI-727 (0.3-3 mg/kg/day, p.o., for 10 days) significantly promoted the spontaneous healing of acetic acid-induced chronic gastric ulcers. Concerning gastric acid secretion, MCI-727 selectively inhibited tetragastrin-stimulated acid secretion without effecting basal acid secretion and acid secretion by other stimuli. Cimetidine and teprenone inhibited acid secretion in several cases. MCI-727 and teprenone had inhibitory effects on gastric motility, although cimetidine had no effect. These results suggest that MCI-727 has a wide spectrum of antiulcer activity, and its mode of antiulcer action is different from that of cimetidine or teprenone. PMID- 1886288 TI - Differences in the antisecretory actions of the proton pump inhibitor AG-1749 (lansoprazole) and the histamine H2-receptor antagonist famotidine in rats and dogs. AB - Antisecretory effects of a substituted benzimidazole, (+/-)-2-[[[3-methyl-4 (2,2,2-trifluoroethoxy)-2-pyridyl]methyl] sulfinyl]-1H-benzimidazole (AG-1749) were compared with those of a histamine H2-receptor antagonist, famotidine. AG 1749 inhibited acid formation regardless of the stimulant in isolated canine parietal cells, while famotidine inhibited the histamine-stimulated acid formation selectively. In pylorus-ligated rats, AG-1749 suppressed basal acid secretion, histamine-, bethanechol-, pentagastrin-, 2-deoxy-D-glucose- and stress (restraint and water-immersion)-induced acid secretion; ID50 values were 1.0-6.0 mg/kg. On the other hand, famotidine only partially inhibited the acid secretion induced by 2-deoxy-D-glucose or stress, although it suppressed the acid secretion stimulated by other secretagogues several times more potently than AG-1749. The antisecretory effect of AG-1749 lasted longer than that of famotidine, especially in the case of bethanechol-stimulated acid secretion. In Heidenhain pouch dogs, both AG-1749 and famotidine potently inhibited histamine-, bethanechol-, pentagastrin- and peptone meal-stimulated acid secretion, but the inhibitory effect of famotidine was short-lived in the case of bethanechol- and pentagastrin stimulated acid secretion. These results suggest that AG-1749 persistently inhibits acid secretion induced by both peripheral and central stimuli and suggest that the antisecretory effect of famotidine depends on the nature of the stimuli. PMID- 1886289 TI - Effects of a proton pump inhibitor, AG-1749 (lansoprazole), on reflux esophagitis and experimental ulcers in rats. AB - The effects of (+/-)-2-[[[3-methyl-4-(2,2,2-trifluoroethoxy-2- pyridyl]methyl]sulfinyl]-1H-benzimidazole (lansoprazole, AG-1749) and famotidine on various experimental ulcers in rats were compared. AG-1749 inhibited reflux esophagitis; gastric lesions induced by water-immersion stress, aspirin or ethanol; and duodenal ulcers induced by cysteamine or mepirizole in a dose dependent manner: the ID50 values were 0.7, 2.4, 0.7, 8.5, 1.1 and 0.3 mg/kg, p.o. or i.d., respectively. Famotidine inhibited reflux esophagitis with an ID50 value of 12.9 mg/kg, but did not cause 50% inhibition of ethanol-induced gastric lesions even at 100 mg/kg, although it showed almost the same or a little stronger potency on other experimental ulcers: ID50 values were 0.3-1.4 mg/kg. Significant aggravation of ethanol- or water-immersion stress-induced lesions was observed in rats given famotidine at 30 mg/kg twice daily for 4 days, but not in rats given AG-1749 at 10 mg/kg twice daily. Administration of AG-1749 for 14 consecutive days markedly accelerated the healing of acetic acid-induced gastric and duodenal ulcers, and the healing effect was significant at 10 and 30 mg/kg/day, p.o. Famotidine also accelerated the healing of ulcers, but its potency was less than that of AG-1749. The results of this study indicate that although AG-1749 is slightly less potent than famotidine in inhibiting acutely induced gastroduodenal lesions, this agent is superior to famotidine in promoting the healing of ulcers and in inhibiting reflux esophagitis and ethanol-induced gastric lesions. PMID- 1886290 TI - Inhibitory effects of beta-phenylethylamine on photic-evoked potentials in the visual cortex of the cat. AB - We investigated the effects of beta-phenylethylamine (PEA) on photic-evoked potentials recorded from the cerebral cortex (visual cortex) in the anesthetized cat. The photic-evoked potential consisted of negative (N) and positive (P) components in the cerebral cortex, with peak times of 39.4 +/- 15.4 msec and 57.5 +/- 16.3 msec, respectively. Intravenous administration of PEA (6.5, 12.5 and 25 mg/kg) induced a dose-dependent decrease in the amplitude of the N component of photic-evoked potentials. PEA-induced decreases in the amplitude of photic-evoked potentials (at 12.5 mg/kg) were antagonized by yohimbine (2 mg/kg). Prazocin (2 mg/kg, i.v.) and propranolol (0.5 mg/kg, i.v.) did not change the PEA-induced decrease of photic-evoked potentials. Methysergide (2 mg/kg, i.v.), haloperidol (1 mg/kg, i.v.) and naloxone (0.5 mg/kg, i.v.) also failed to alter the inhibitory effect of PEA. Pretreatment with alpha-methyl-p-tyrosine or reserpine did not completely attenuate the PEA-induced decrease of photic-evoked potentials. According to these results, PEA inhibits the photic-evoked potentials in the visual cortex partially through the noradrenergic alpha 2-receptor. PMID- 1886291 TI - Hyperuricemia induced by the uricosuric drug probenecid in rats. AB - Stimulation of uric acid production by the well-known uricosuric drug probenecid was studied using potassium oxonate-treated rats and eviscerated rats subjected to functional hepatectomy. In oxonate-treated rats, probenecid was hyperuricosuric, increasing the glomerular-filtered amounts of uric acid and causing marked hyperuricemia. This could be completely blocked by combination dosing with allopurinol, an inhibitor of xanthine oxidase. In eviscerated rats subjected to functional hepatectomy, probenecid also increased plasma uric acid and urinary uric acid excretion, but when given together with allopurinol, the increase of plasma uric acid was abolished with a remarkable increase of plasma hypoxanthine and xanthine. When probenecid was given by combination dosing with propranolol, a beta adrenoceptor antagonist, the hyperuricemia was also completely blocked. Thus, probenecid is concluded to stimulate uric acid production, probably via some interaction with endogenous catecholamine, resulting in hyperuricemia in rats, although it is a practical hypouricemic drug in humans. PMID- 1886292 TI - Effects of muscarinic antagonists on experimental nasal secretion in guinea pigs. AB - The effects of muscarinic antagonists on acetylcholine (ACh)- and histamine induced nasal secretion were investigated in guinea pigs. Inhalations of flutropium (0.01 to 0.3%) and atropine (0.03 to 0.3%) into the nasal cavities dose-dependently inhibited the nasal secretion induced by ACh. The inhibitory action of flutropium was slightly stronger than that of atropine. Inhalations of pirenzepine (0.3%) and gallamine (0.3%) had no effect on the ACh-induced nasal secretion. However, 4-DAMP dose-dependently inhibited the nasal secretion induced by ACh. Inhalations of flutropium (0.3%) and diphenhydramine (0.3%) showed a similar inhibitory action on the histamine-induced nasal secretion. These results suggest that 1) inhalation into the nasal cavities of flutropium was effective in experimental model of ACh- and histamine-induced nasal secretion, 2) M3 cholinergic receptors may be dominant in the nasal secretion induced by ACh and 3) the experimental model of drug-induced nasal secretion in guinea pigs used in the present study can be employed to develop therapeutic drugs for nasal secretion. PMID- 1886293 TI - 9-Amino-1,2,3,4-tetrahydroacridine is a potent inhibitor of histamine N methyltransferase. AB - The effect of 9-amino-1,2,3,4-tetrahydroacridine (THA) on histamine N methyltransferase (HMT), an enzyme catalyzing the methylation of histamine to form tele-methylhistamine in the brain, was studied in vitro using a partially purified enzyme preparation from bovine brain and in vivo in the mouse brain. THA inhibited the HMT activity in competitive and non-competitive mixed type manners with respect to histamine. The Ki and Ki' values were 75 nM and 1.2 microM, respectively. The IC50 values for THA, 9-aminoacridine and physostigmine in the inhibition of HMT determined at fixed concentrations of histamine (20 microM) and S-adenosylmethionine (50 microM) were 0.2, 0.37 and 20 microM, respectively. Neostigmine exhibited only 15% inhibition even at a concentration of 100 microM. THA (2-10 mg/kg, s.c.) dose-dependently inhibited HMT in the mouse brain. The inhibition of HMT by THA (10 mg/kg) was marked at 30 and 60 min after treatment, but disappeared by 120 min after. THA (10 mg/kg) significantly increased the histamine level and decreased the tele-methylhistamine level in the mouse brain. These results indicate that THA is a potent inhibitor of HMT. PMID- 1886294 TI - Endotoxin- and inflammation-induced depression of the hepatic drug metabolism in rats. AB - Carrageenan-induced inflammation and exposure to endotoxin considerably decreased the content of cytochrome P-450 and activities of ethylmorphine N-demethylase and meperidine N-demethylase, but did not decrease the activities of aniline hydroxylase or NADPH-cytochrome c reductase, compared with the respective activities in rats treated with carrageenan alone. These results suggest that under these experimental conditions, the two host-related environmental factors interact and enhance a decrease in rat hepatic microsomal drug metabolizing enzymes depending on the substrate used. PMID- 1886295 TI - [Effect of posture on pharyngeal area measured by acoustic reflection technique]. AB - Patients with obstructive sleep apnea (OSA) have a smaller pharyngeal area (PA) and higher compliance than normal subjects. The apnea-hypopnea index (AHI) in OSA patients determined by polysomnographic study was greater in the supine than lateral position. Recently there have been reports of reduction in the PA by the acoustic reflection technique (ART) in the supine position. However, there has been no report on the PA measured by ART in the lateral position which is important in the treatment of OSA. To evaluate differences in the PA with posture changes, we measured the PA in 41 normal subjects (11 males and 30 females) in the sitting, lateral and supine positions by ART. The average PA in the sitting position in the males and females was 3.8 +/- 0.6 cm2, and 3.3 +/- 0.5 cm2, respectively. The average PA in the lateral position in the males and females was 3.5 +/- 0.6 cm2, and 3.1 +/- 0.5 cm2, respectively. The average PA in the supine position in the males and females was 2.9 +/- 0.5 cm2, and 2.7 +/- 0.4 cm2, respectively. PA in the sitting position correlated well with body surface area (BSA). The average PA in both the males and females was significantly smaller in the supine than in the sitting position. The average PA in the lateral position in both males and females was significantly smaller than that in the sitting position and was significantly larger than that in the supine position. Decrease in PA with posture (from sitting to lateral) in the males (9.2 +/- 5.5%) was similar to that in the female (5.7 +/- 5.4%). Decrease in PA with posture (from sitting to supine) was significantly larger in male (24.4 +/- 9.5%) than in female (16.6 +/- 6.8%). We conclude that the decrease of PA in the supine position is ameliorated in the lateral position in normal subjects. Lateral position may be the preferred sleeping position in snoring or OSA patients. PMID- 1886296 TI - [Analysis of factors of increased phase differences between chest flow and mouth flow at rest breathing in patients with obstructive disorders]. AB - The factors which increase phase differences between mouth flow and chest flow in patients with obstructive disorders were analyzed. From airway resistance, thoracic gas volume and measured chest flow, phase difference was predicted by the Runge-Kutta (R.K.) method assuming respiratory system to be a single compartment model. The ratio of the measured phase differences to the predicted value by the R.K. method in normal subjects was 0.99 +/- 0.25. These results suggest that a single compartment model can be applied to normal respiratory system. In contrast, predicted phase differences were remarkably higher than measured values in patients with obstructive disorders (CPE: 1.83 +/- 0.63, DPB: 1.50 +/- 0.48). This phenomenon could be explained by the existence of parallel inhomogeneity of alveolar pressure. PMID- 1886297 TI - [Effects of nasal continuous positive airway pressure (NCPAP) on nocturnal renal function in obstructive sleep apnea syndrome (OSAS)]. AB - Nocturnal renal function was examined in 8 patients with obstructive sleep apnea syndrome (OSAS) and the effects of nasal CPAP (NCPAP) on renal function were also studied. Nocturia was observed more than twice in all cases when no treatment was performed, but it disappeared after initiation of NCPAP. Fractional nocturnal urine volume and creatinine clearance decreased significantly from 1.36 +/- 0.15 ml/min to 0.75 +/- 0.20 ml/min (p less than 0.01) and from 116.8 +/- 46.5 ml/min to 101.1 +/- 33.0 ml/min (p less than 0.05), respectively, after initiation of NCPAP. Although the serum Na and creatinine did not change following NCPAP, the urine Na and creatinine changed significantly after NCPAP therapy. The serum renin, aldosterone, and ADH did not change after NCPAP therapy. The significant positive correlation (p less than 0.05) between the fractional nocturnal urine volume and DI, and also significant inverse correlation (p less than 0.05) between the fractional urine volume and %FRC were observed. These results suggest that the abnormal renal function seen in cases of OSAS is related to the hypoxemia during sleep. It was concluded that the nocturnal renal function in cases of OSAS was different from those in normal controls and NCPAP therapy induced the recovery of these abnormalities. PMID- 1886298 TI - [Radiographic visualization of pleural space under negative pleural pressure]. AB - Although many imaging modalities have developed in the area of pulmonary medicine, information about the condition of pleural surface is limited. In this study, we carried out contrast pleurography under negative pleural pressure in dogs and humans to evaluate the condition of the pleural space including adhesion between the two pleural layers, incomplete fissure and features of the pleural surface. After insertion of a flower-type catheter into the pleural space under ultrasonic guidance, contrast material (60% Meglumine iotalamate, Conray 60, 0.5 1.0 ml/kg) was injected into the pleural space through the catheter. In dogs with intact pleura, contrast material distributed to the pulmonary surface, including interlobar spaces, rapidly. In dogs with pleural adhesion which was induced artificially with talc, affected areas were visualized as defects of contrast material. In humans, this contrast pleurography provided information about pleural adhesion, pulmonary lobulation, extent of cancer to neighbouring lobes, irregular pleural surface due to bullae formation and pleural indentation by cancerous lesion. There was no serious complication in dogs and human studies. This contrast pleurography is unique because it is possible to evaluate the pleural space physiologically under negative pressure condition. It may be concluded that this method of pleurography is useful for the clinical evaluation of the condition of the pleura in various lung diseases. PMID- 1886299 TI - [Familial outbreak of psittacosis]. AB - Three familial cases of psittacosis are reported. The first case was a 46-year old woman, the second case, her 18-year-old daughter. Both of them often visited the house of the third case, a 49-year-old women, who was the elder sister of case 1 and who took care of the chick of a budgerigar which she kept in the house. Case 1 came to our hospital with abrupt onset of fever, headache, nausea and general malaise. Because she was suspected to have meningitis, she was admitted to the Department of Neurology. On admission, her chest X-ray film showed bilateral ground glass shadows. She also had hypoxemia and liver dysfunction. On learning of her history of contact with the chick, psittacosis was suspected. Case 2 suffered from fever and headache. Her chest X-ray film revealed opaque infiltration in the right lower lung field. Case 3 complained of fever, headache and vomiting. Her chest X-ray film showed fan-shaped faint shadows in the left upper, middle and lower lung fields. We interpreted these findings as showing psittacosis based on anamnesis. The result of the complement fixation (CF) antibody titer against chlamydia was 1:32 in cases 2 and 3, enabling a serological diagnosis of psittacosis. The corresponding result was 1:16 in case 1. Although the CF antibody titer showed no increase, we diagnosed the case clinically as psittacosis. It is difficult to correctly diagnose psittacosis only from the physical findings and chest X-ray films. Detailed anamnesis, in particular taking a history of exposure to birds, is an important clue for diagnosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1886300 TI - [A case of accessory cardiac bronchus with acute empyema treated by open drainage]. AB - A 40-year-old man was admitted to the hospital because of acute empyema localized in the right lower posterior pleural space. The conservative treatment with antibiotics for one month failed to show any clinical improvement. Surgical intervention, therefore, was required. Broncho-fiberscopic and bronchographic findings prior to open drainage revealed a supernumerary bronchus with inflammatory sign on the right intermediate bronchus and a small sprig like bronchial fistula attached to the tip of the abnormal bronchus. The operation induced the swift alleviation of empyema and the disappearance of bronchial inflammation. From the location of empyema and the disappearance of bronchial inflammation associated with the improvement of clinical findings, the infection of the abnormal bronchus was thought as a main cause of empyema. Empyema caused by this kind of abnormality is extremely rare and no similar case has been reported in the literature to our knowledge. Some pathological problems of the abnormal bronchus were discussed and 54 cases of accessory cardiac bronchus reported in Japan were reviewed. PMID- 1886301 TI - [A case of inflammatory pseudotumor of the lung that extended to involve the mediastinum]. AB - A 17-year-old woman was referred to our hospital because of cough and fever. The chest X-ray films revealed an anterior mediastinal mass shadow. Steroid drugs and antibiotics were administered and the shadow diminished slightly. To confirm diagnosis, open thoracotomy was performed. The tumor was extended to the mediastinum, thymus and heart as well as the right middle lobe and right lower lobe. Microscopic findings of the resected tumor showed proliferation of histiocytes with infiltration by inflammatory cells, lymphocytes and fibrous tissue. PMID- 1886302 TI - [Two cases of interstitial pneumonitis with marked increase of tumor-associated carbohydrate antigens in serum]. AB - Tumor-associated carbohydrate antigens, CA19-9 and SLEX have been used clinically as markers for malignancy. However, it is also known that these antigens are frequently elevated in the serum of patients with benign lung diseases. We have experienced two cases of interstitial pneumonitis with marked increase of carbohydrate antigens in serum, the level of which changed according to their clinical course. Case 1. A 64-year-old woman was admitted because of a cough and exertional dyspnea. Despite treatment with various antibiotics and prednisolone, she died of respiratory failure approximately two months after admission. Her CA19-9 and SLEX in serum elevated from 500 U/ml to 5506 U/ml and 167 U/ml to 1187 U/ml respectively in accordance with clinical deterioration. Autopsy revealed no malignancy. Case 2. A 57-year-old woman, who had been suffering from interstitial pneumonitis associated with rheumatoid arthritis, was admitted with a cough and fever. She responded to prednisolone therapy, however two years later she readmitted because of exacerbation and died of respiratory failure. The initial CA19-9 level in serum was 876 U/ml and dropped to 42 U/ml with prednisolone therapy. The serum antigen level again increased during the period of exacerbation, and showed 133 U/ml immediately before death. An immunohistochemical study of CA19-9 and SLEX in various tissues obtained by autopsy was performed in case 1. The distribution of these antigens in tissue was similar to that of normal individuals. The exceptions were the expression of these antigens on epithelial cells of microscopic honeycombing and on mucinous exudates in air spaces. PMID- 1886303 TI - [A case of solitary bronchial papilloma and a review of the literature]. AB - A case of solitary bronchial papilloma which is one of the rarest of pulmonary benign tumors is reported. A 25-year-old male was admitted to our hospital with an abnormal chest shadow. Bronchoscopy revealed a tumor at the orifice of left B6. The biopsy specimen of the tumor was diagnosed as a papilloma. Left S6 sleeve segmentectomy was performed to preserve lung function. The tumor was like a cauliflower and 4 x 4 x 4 cm in size. The histological diagnosis was bronchial papilloma. Since there are some reported cases of solitary bronchial papilloma with carcinoma in situ, such cases must be treated surgically when possible. PMID- 1886304 TI - [Observation of bleeding sites by fiberoptic bronchoscopy in a case of vasculo Behcet's disease with pulmonary involvement]. AB - A 45-year-old man complained of fever and bloody sputum. Chest X-ray films showed a round opacity in the left hilum. He developed massive hemoptysis (500 ml) and emergency embolization of the bronchial artery was performed. Pulmonary artery aneurysm and thrombosis were detected angiographically, and fiberoptic bronchoscopy revealed a reddish irregular eminence of the left main bronchus and lingulate++ ++ bronchus. These sites could have been the bleeding sites. Because of recurrent hemoptysis, left pneumonectomy was performed 26 days after the massive hemoptysis. Pathological findings showed panarteritis, luminal thromboembolism of the pulmonary artery and markedly dilated vessels of the bronchial wall. He developed genital ulceration after the operation and these findings suggested incomplete vasculo-Behcet's disease with rare pulmonary involvement. The disease is now well-controlled by corticosteroid therapy 27 months after the operation. PMID- 1886305 TI - [A case of pulmonary alveolar microlithiasis showing respiratory failure after 33 years and revealing microliths in bronchoalveolar lavage]. AB - A 43-year-old woman was admitted to our hospital because of dyspnea and anorexia. She had hypoxia and cyanosis. The chest roentgenogram revealed dense reticular, partly nodular shadow and emphysematous bullae in both lung fields. An abnormal chest X-ray had been pointed out and pulmonary alveolar microlithiasis had been diagnosed 33 years previously. Bronchoscopy and bronchoalveolar lavage were performed and calcium microliths were seen in the bronchoalveolar lavage fluid smear. Bronchoalveolar lavage appears useful in the diagnosis of pulmonary alveolar microlithiasis. A series of X-ray findings showed development of emphysematous bullae, niveau formation and disappearance of bullae. These changes seem to reveal the progress of her disease from the established stage to the advanced stage. Such a case of pulmonary alveolar microlithiasis over the course of a long period is rare. PMID- 1886306 TI - [Cervical lung hernia in a case of severe chronic asthma and bronchitis]. AB - A case of a bilateral pulmonary hernia of the lungs into the supraclavicular fossae is described. A man, aged 79, with severe chronic asthma and chronic bronchitis due to air pollution, complained of a cervical mass off and on for several years. The herniation was greater on the right side. It could be identified on physical examination by the presence of a soft painless supraclavicular bulge which was exaggerated by strain or cough. Radiologically this herniation could best be identified on lateral cervical roentgenogram. It is said that cervical lung hernia is a rare condition, but in our experience supraclavicular herniation of the lung is not unusual in cases of severe chronic obstructive lung disease. PMID- 1886307 TI - [Observations of the fibrosing process in paraquat lung injury by chest X-ray and CT]. AB - A 42-year-old woman with a known history of paraquat ingestion was admitted to our hospital on the 10th day after ingestion complaining of dyspnea and general fatigue. Steroid therapy and low dose oxygen therapy were administered. She recovered and was discharged on the 190th day after paraquat ingestion. A chest X ray film on admission disclosed a bilateral ground-glass shadow. As time passed, a reticular shadow with a loss of lung volume leaving a peripherally clear zone appeared on chest X-rays and shrank gradually toward the peri-hilar area during the course. CT of the lung clearly demonstrated progress of the pulmonary fibrosing process. In the early phase of paraquat poisoning, CT revealed diffuse high density areas dominant in the posterior part of the lungs with a subpleural intact area. The high density area was sharply demarcated from the subpleural intact area. As time passed, the high density area shrank toward the central zone, causing bullous changes in the subpleural area. The dominant fibrotic change in the intermediate and central zones seems to be one of the characteristic findings in paraquat induced pulmonary fibrosis. PMID- 1886308 TI - [Old pulmonary embolism causing intrabronchial bleeding]. AB - A 51-year-old man was admitted because of hemoptysis. Physical examinations and chest XP revealed no abnormal findings. Fiberoptic bronchoscopy showed pulsatile bleeding at the orifice of right B6. Right bronchial arteriography showed a markedly dilated and tortous bronchial artery and shunting to the pulmonary arterial system in the middle and lower lobes. Pulmonary arteriography showed complete obstruction of the right middle lobar and lower lobe segmental arteries (A6, 9, 10). The hemoptysis was thought to be due to increased blood flow of the right bronchial artery, which compensated for reduced right pulmonary arterial flow. Right middle and lower lobe resection was done to prevent further hemoptysis. The resected specimen revealed old thromboemboli in the right middle and lower lobe pulmonary arteries. In this case old pulmonary embolism should be considered as a cause of intrabronchial bleeding. PMID- 1886310 TI - [Treatment of aneurysms of the aortic arch]. AB - Graft replacement therapy was employed in the treatment of 28 patients with aneurysms involving the aortic arch. Of the 28 patients, 14 had true aneurysms, 13 dissecting aneurysms, and 1 pseudoaneurysm. The operative mortality was 75% (6 of 8 patients) between 1979 and 1986, whereas it was 10% (2 of 20 patients) between 1987 and 1989. Temporary or permanent bypass with vascular graft or heparin coated tube were used in 10 patients (7 patients in the early period, 3 patients in the later period). In this group, 50% hospital mortality occurred. Cardiopulmonary bypass and separate cerebral circulation were used in 16 patients (1 case in the early period, 15 patients in the later period). Thirteen of 16 patients survived this technique. In 2 patients, both in later period, profound hypothermia and circulatory arrest were used. Two patients survived without neurological deficit. Operative mortality decreased since 1987 by the change of bypass technique and operative procedures. PMID- 1886309 TI - [A case of jejunal metastasis from pulmonary adenocarcinoma occurring as perforative peritonitis]. AB - On first admission on June 5, 1989, pulmonary adenocarcinoma of left S3b in a 62 year-old male had already metastasized to the brain and the clinical stage was T2N2M1. Radiation therapy for the metastatic brain lesion was very successful but chemotherapy for the primary lesion was not effective. He was discharged on August 24, 1989. He was readmitted to our hospital on Jan. 5, 1990 because of severe abdominal pain. His chest roentgenogram showed free air under the diaphragm. An emergency laparotomy was performed, because perforation of gastrointestinal tract was suspected. At operation, two localized tumors were found, one located in the jejunum approximately 20 cm distal to the ligament of Treitz, accompanied by perforation and another approximately 20 cm distal to the above lesion in the mesentery. The resected specimen of the perforated lesion demonstrated a deep and large ulcer, compared to the tumor size, similar to a submucosal tumor, accompanied by bridging folds. The pathologic interpretation was adenocarcinoma of the lung metastatic to the jejunum and mesentery. Primary lung cancer metastasizes to a wide variety of organs, but metastasis to the small intestine is uncommon, even on postmortem examination. Furthermore, it is rare that the metastatic lesion causes abdominal symptom leading to laparotomy. PMID- 1886311 TI - [Surgical repair of postinfarction cardiac rupture in three cases]. AB - Operative managements and results of postinfarction left ventricular (LV) rupture in 2 patients and right atrial (RA) rupture in one patient are reviewed. Two patients showed both subacute onset of LV rupture in association with cardiac tamponade. The site of infarction was inferior wall in one and anterior wall in the other. Both patients underwent infarctectomy with closure of the defect using a Dacron felt patch. Endocardial site of the Dacron patches were covered with own pericardium to avoid bleeding from the patch and postoperative complication of endocardial clot formation. The case with extended inferior wall infarction was succumbed to cardiac failure and acute renal failure at the twelfth postoperative day. The other case was uneventful postoperatively and shows excellent long-term result. Left ventriculography and coronary angiographic studies were carried out 3 months after the surgery. It demonstrated 43% of LVEF. Multiple stenotic lesions were also noted in left coronary artery. The third patient was rupture of the RA in association with cardiac tamponade. Direct suture closure of the rupture was carried out under extracorporeal circulatory support. Patient tolerated the procedure well. Postoperatively, he suffered from exacerbation of renal insufficiency necessitating hemodialysis for a month. He discharged from hospital and now in the good condition. Postoperative RI study and coronary angiography demonstrated no compatible finding of right atrial infarction. However, pathological specimen revealed definite diagnosis of the infarction at the RA appendage. PMID- 1886312 TI - [Analysis of factors influencing early patency of saphenous vein grafts]. AB - To determine factors affecting early patency of saphenous vein grafts, 140 grafts in 65 patients were studied angiographically within 2 months after operation. Twenty of the 140 grafts were occluded. Sixteen variables were extracted from the angiographic findings, intraoperative measurements, clinical characteristics, and biochemical data. The univariate and multivariate analyses were performed to assess their predictive value. Of 16 variables, 3 (coronary artery internal diameter, graft flow, and coronary artery resistance) correlated significantly with graft patency in the univariate analysis. The multivariate analysis selected coronary artery resistance, coronary artery internal diameter, and degree of proximal stenosis as predictors of early graft patency. Of these 3 factors, the coronary artery resistance influenced graft patency mostly. Therefore, the coronary artery resistance was considered to be the most reliable predictor of early graft patency. PMID- 1886313 TI - [A case of left main bronchial rupture due to bronchocath tube]. AB - A 68-year-old woman underwent a right upper lobectomy for lung cancer. After resection, we noticed the left main bronchial rupture due to bronchocath tube (polyvinyl chloride double lumen tube). The lesion of the rupture was repaired by interrupted sutures with 4-0 prolene. Subsequent course of the patient was uneventful. Tracheobronchial rupture is rare complication of intubation with polyvinyl chloride double lumen tube. There are 6 cases of this complication last five years in Japan. The cause and prevention of this complications are described. It is important to use an adequate tube size, to prevent malposition of the tube and overinflation of the bronchial balloon. PMID- 1886314 TI - [New method for enlargement of narrowed aortic annulus: intra-arterial aorto infundibuloplasty]. AB - A new procedure of "intra-arterial aorto-infundibuloplasty" for the narrowed aortic annulus is described. Aortic valve replacement can be performed through the aorto-pulmonary and infundibular septal incision which is eventually enlarged by a single patch. PMID- 1886315 TI - [Subarachnoid hemorrhage following commencement of danazol treatment in a patient well controlled on warfarin anticoagulation]. AB - A 45-year-old woman with prosthetic valves replacement, was admitted with severe headache and vomiting one month after starting danazol treatment at 300 mg per day. She was receiving long-term anticoagulation with warfarin and dipyridamole, taking 3.5 mg and 300 mg per day respectively. The patient's thrombotest value was less than 6% at the time of admission. Cranial CT revealed subarachnoid hemorrhage. Warfarin and danazol treatment ware discontinued with replenishment of vitamin K. Recovery was uneventful. Danazol is 2, 3 isoxazol derivative of 17 alpha-ethinyl testosterone. As such, it shares the property of C 17 alkylated steroids in potentiating the action of coumarin. It is suggested that danazol affects the turnover of vitamin-K-dependent clotting factors, an impairment of synthesis being a likely mechanism. The possible hazard of the potentiating effect of danazol on warfarin should be widely appreciated. PMID- 1886316 TI - [Evaluation of treatment of lung cancer combined with the disease which has needed a semi-emergency operation]. AB - Six cases of lung cancer combined with the disease which has needed semi emergency operation, two cases of unstable angina, two of ileus due to colon cancer, one of impending rupture of abdominal aortic aneurysm and one of purulent cholecystitis with cholelithiasis, were discussed. Mean age was 62.0 years (range, 36 to 73); four were male and two were female. Case 1 and 2 were admitted with anterior chest pain, Case 3 with lumbago and abdominal pain, Case 4 and 5 with an abnormal shadow on chest x-ray film and Case 6 with abdominal pain. Of the two with unstable angina, one was operated on with right upper lobectomy during the first months after aorto-coronary bypass. Of the two with colon cancer, one was operated on with right upper lobectomy during about 5 weeks after right hemi-colectomy. Case 3 with abdominal aortic aneurysm operated on with left upper lobectomy during 4 weeks after replacement of abdominal aorta. Case 4 with cholecystitis was operated on with left pneumonectomy during about 3 weeks after cholecystectomy. The postoperative course of 4 cases and the post-chemotherapy condition of 2 cases were uneventful. PMID- 1886317 TI - [Informed consent in cardiac surgery]. AB - Recently, it has been recognized in Japan that informed consent is indispensable to make decisions for medical treatment, although it had been already confirmed in western countries for several decades of years. However, there may be some differences in the content of informed consent between Japan and western countries. We discussed the problems of informed consent in Japan concerning the choice of prosthetic valve, mechanical prosthesis or bioprosthesis, in patients to be undergone valve replacement. We conclude that informed consent should be the humane relationship between therapists and a patient. PMID- 1886318 TI - [Combined operation for left atrial myxoma, mitral regurgitation, coronary artery stenosis and abdominal aortic aneurysm]. AB - A 68-year-old male patient with a left atrial myxoma, mitral regurgitation, ischemic heart disease and abdominal aortic aneurysm underwent resection of the myxoma, mitral valve replacement, 4 coronary artery bypass grafting and replacement of the aneurysm simultaneously. The aneurysm was replaced under partial cardiopulmonary bypass. Combined cardiac and abdominal aortic operation is useful in selected patients who require IABP support postoperatively or whose cardiac function is poor. PMID- 1886319 TI - [Tricuspid endocarditis related to a residual ventricular septal defect: a case report of successful tricuspid valvuloplasty]. AB - A 5-year-old girl presented infected tricuspid valve related to a residual ventricular septal defect. Antibiotic therapy produced a satisfactory initial improvement. However, subsequent deterioration with uncontrolled infection, in spite of alterations of the antibiotic regime, necessitated surgical intervention. Because the lesion was localized to the anterior leaflet of the tricuspid valve, partial excision of this leaflet and patch was undergone with a sustained clinical improvement with minimum residual valvular incompetence. This experience supports the concept that tricuspid valvuloplasty is the method of choice in the treatment of patient with regional right-sided infective endocarditis. PMID- 1886320 TI - [Spontaneous pneumothorax in pregnancy: a case report and review of the literature]. AB - Spontaneous pneumothorax in pregnancy is said to be a rare condition. A 37-year old woman at 13 weeks' gestation with this rare complication, was reported. The patient was first treated by chest tube drainage, which failed to get complete reexpansion of the lung, and she was managed by thoracotomy twenty days after. She delivered, at full term, a healthy normal infant by cesarean section. Indications for operative treatment of pneumothorax in pregnancy, in general, are not absolutely defined. We believe that the usually accepted indications for operation, such as persistence of air leakage despite adequate drainage and multiple recurrences of pneumothorax, are valid during pregnancy, if the patient allows the pregnancy to proceed. PMID- 1886321 TI - [Surgical treatment of PDA in the elderly patient accompanied with aneurysm of the main pulmonary artery]. AB - A case of the elder PDA with aneurysm of the main pulmonary artery is reported. The patient was a 59-year-old female who had been suffering from severe heart failure. The PDA was closed directly from inside of the pulmonary artery using balloon catheter under usual cardiopulmonary bypass with limited circulatory arrest, and the aneurysm was repaired by aneurysmorrhaphy. The postoperative course was uneventful and she was discharged after 34 postoperative days. The pathological finding of the aneurysm of the main pulmonary artery is a cystic mucoid degeneration like a finding of Marfan syndrome. The etiology of the aneurysm of the main pulmonary artery seems to be extended Ao-PA shunt besides somewhat congenital change of the pulmonary artery. PMID- 1886322 TI - [Surgical treatment of ruptured descending aortic aneurysm to the right extra thoracic space: a case report]. AB - A fifty-nine year-old woman was emergently admitted to our hospital for the aneurysm in descending aorta. She complained of severe back pain and dysphagia, and showed extreme hypotension. Aortic angiography was performed immediately. It revealed the aneurysm of descending aorta (phi 7.2 cm) and abdominal aorta (phi 3.5 cm), and also showed obstruction of bilateral common iliac arteries. On chest X-ray, a diffuse shadow of the right-sided chest was found. Through chest drainage, fresh blood was let out from extrapleural space. On the next day, the drainage blood markedly increased. Subsequently, emergent operation was performed. The operation consists of resection of aortic aneurysm with grafting and aortofemoral bypass with a Y shaped graft. The patient survived the operation and was discharged without any disability. PMID- 1886323 TI - [A case report of atypical coarctation of the aorta with coarctation and left subclavian arterial aplasia]. AB - A 18 year-old female was admitted to our hospital with hypertension of 190/100 mmHg in her right arm and 140/110 mmHg in the left arm. Femoral arterial pulsation was not palpable. Her physical status and growth of the lower limbs were normal. Aortography demonstrated slight coarctation with a pressure gradient of 10 mmHg and descending aortic stenosis with a pressure gradient of 80 mmHg. Main three branches from aortic arch were anatomically normal. However, the left subclavian artery distal to the origin of the left vertebral artery was not visualized and the axillary artery was perfused by collaterals. Atypical coarctation was replaced using a woven Dacron graft of 14 x 40 mm. Postoperatively proximal pressure decreased from 180/113 to 156/98 mmHg and there was no pressure gradient between proximal and distal of the graft. After six months blood pressure in the right arm gradually decreased to 120/78 mmHg. PMID- 1886324 TI - [A case of perforation of the metastatic site of lung carcinoma in the small bowel]. AB - Metastasis of lung carcinoma in the small bowel is so extremely rare as there were 53 cases in total with small bowel metastasis from lung carcinoma reported in the past literature. A case of a 72-year-old man with unresectable lung carcinoma (squamous cell carcinoma) was reported, he had an acute perforation of the small bowel following intensive course of irradiation therapy for primary site. Emergency operation was performed, but he died of DIC (disseminated intravascular coagulation) 3 days after surgery. PMID- 1886325 TI - [Biosynthesis of insulin: intracellular traffic and enzymatic transformations]. PMID- 1886326 TI - [Role of amylin in the physiologic and physiopathologic regulation of energy metabolism]. PMID- 1886327 TI - [Beta cells in Type II diabetes: culprit or victim?]. PMID- 1886328 TI - [The endogenous ligand of sulfonylurea receptors]. PMID- 1886330 TI - [Vanadium and diabetes]. PMID- 1886329 TI - [Magnesium and the regulation of carbohydrate metabolism]. PMID- 1886331 TI - [Inhibitors of alpha-glucosidase]. PMID- 1886332 TI - [Role of fish oils in diabetic dietetics]. PMID- 1886333 TI - [The education of the diabetic patient: summary of his history. The results and the problems of today]. PMID- 1886334 TI - [Educational diagnosis and evaluation of educational strategies (PRECEDE Model): practical methodology for inducing changes in behavior and health status]. PMID- 1886335 TI - [Sociocultural factors implicated in the establishment of therapeutic protocols and their consequences for the individual]. PMID- 1886336 TI - [Conformational changes in lipoproteins containing apo B: significance of monoclonal antibodies]. PMID- 1886337 TI - [Diagnosis and evaluation of educational strategies for non-insulin-dependent diabetics and their treating physicians in France]. PMID- 1886338 TI - [Apollinaire Bouchardat 1991 Award. Insulin resistance in an animal model of hypoinsulinism]. PMID- 1886339 TI - [Maurice Derot 1991 Award. Diabetogenic and atherogenic fat]. PMID- 1886340 TI - [Liaison of apolipoprotein A with adipose cells: characteristics of the receptor sites and their role in the efflux of cholesterol]. PMID- 1886341 TI - [The new insulins: a result of molecular biology prowess, maybe a clinical advance?]. PMID- 1886342 TI - [Hyperthyroidism and glucose metabolism]. PMID- 1886343 TI - [Pancreatic transplantation in man]. PMID- 1886344 TI - [Molecular methods of genome analysis]. PMID- 1886345 TI - [Epidemiology of Type I diabetes: the Spanish experience. Iddm Study Group]. PMID- 1886347 TI - [Proceedings of the 83d annual meeting of the Swiss Ophthalmologic Society. 13-16 September 1990, Crans-Montana]. PMID- 1886346 TI - [Hemostasis anomalies in sugar diabetes]. PMID- 1886348 TI - [Effect of betaxolol and timolol on visual fields in glaucoma patients]. AB - In a prospective, randomized, double-masked study, primary open-angle glaucoma patients were treated twice daily with either betaxolol 0.5% or timolol 0.5%. Patients received a pretreatment baseline examination following a 2 week washout period; they were then examined after 3 and 6 months of treatment. Each examination included visual field measurements with an Octopus automated perimeter and intraocular pressure measurement. The visual fields of the betaxolol group showed on the average a pronounced tendency toward improvement (MD decrease of 2.05 dB); visual fields in the timolol group showed a slight tendency toward improvement (MD decrease of 1.56 dB). The difference between these 2 trends after 6 months was statistically not significant (p greater than or equal to 0.05, U-test). Both drugs lowered intraocular pressure, there was no significant difference between the two drugs (p greater than or equal to 0.05, U test). PMID- 1886349 TI - [Treatment of normal pressure glaucoma with a serotonin S2 receptor antagonist, naftidrofuryl (praxilen)]. AB - 35 normal tension glaucoma patients were followed during 8 to 11 month. 12 patients received 2 x 200 mg/day Naftidrofuryl, a serotonine S2 receptor antagonist. As controles, another 23 patients were followed without treatment. The treated group, compared with the 23 non treated patients showed a significant increase in visual acuity (p = 0.001), a significant increase of the MS (p = 0.03), and a non significant decrease of the MD and CLV on the Octopus visual field (p, NS). The physiology and physiopathology of serotonine and S2 receptor antagonist are discussed. PMID- 1886350 TI - [Pseudoexfoliation syndrome]. AB - The Frequency of the Pseudoexfoliation-Syndrom (= PES) was investigated about two months in a prospective study of 1069 patients in the university eye hospital of Zurich. 7.35% of these patients had a PES with or without glaucoma. Among the clinic patients there were 9.9% and among the policlinic patients 6.26%. All our patients were elder than 60 years old, 58.9% between 70-85 years. There were 33.37% men and 66.63% women. 33% of the PES-patients had a tension over 22 mmHg. 42.86% of the patients had the highest tension over 30 mmHg. 33.33% (= 26 patients) had a PES without glaucoma and 66.66% (= 52 patients) a PES with glaucoma. 56.42% of the patients (= 44 patients) had in one eye PES and 43.58% (34 patients) in both eyes. 9.61% (= 5 pat.) had an absolute PES-glaucoma in one eye. PMID- 1886351 TI - [Comparison of the anti-miotic effect of 0.03% flurbiprofen with 1% indomethacin in cataract extraction]. AB - Maintaining successful mydriasis is essential during cataract extraction. The use of nonsteroidal anti-inflammatory drugs in order to inhibit trauma induced miosis has been advocated by many authors. Indomethacin 1% has proved his efficacy since many years. Flurbiprofen has been introduced more recently and has been accepted largely because of a better patient comfort. He proved his efficacy against placebo. We conducted a randomized double blind study in order to verify if there is any difference in efficacy between these two drugs. 40 cases were randomly assigned to a pretreatment, not known by the surgeons, with Indomethacin 1% (Indoptic) or Flurbiprofen 0.03% (Ocuflur). Measurements were taken at the beginning of surgery, after nucleous extraction and after irrigationaspiration of lens cortical material. Sodium hyaluronate and epinephrine were not used during this study. After nucleous extraction, the mean pupillary constriction was 1.53 mm in the Indomethacin group and 1.23 mm in the Flurbiprofen group (p greater than 0.1). After aspiration of cortical material, the mean pupillary constriction was 2.27 mm in the Indomethacin group and 2.00 in the Flurbiprofen group (p greater than 0.1). Cumulative results of patients who constricted the pupil more than 2 and 3 mm showed a better result in the Flurbiprofen group. Flurbiprofen has proved in this study his efficacy compared to an other nonsteroidal anti inflammatory drug in inhibiting trauma induced miosis. PMID- 1886352 TI - [Complications of cataract surgery. Retrospective study of 1,304 cases]. AB - This retrospective study concerns complications arising from 1304 first operations for cataract carried out between 1982 and 1987 by two surgeons having followed the same training and using the same techniques. Loss of vitreous (2.5%) cystoid macular edema (1.9%), and retinal detachement (1.1%) are those complications occurring most frequently in this series. Other serious complications, in descending order, are trauma (0.7%), iris prolaps (0.5%), corneal dystrophy (0.4%), pupillary block (0.3%), expulsive hemorrhage (0.15%), loss of the nucleus in the vitreous (0.07%), panophthalmia (0.07%). Secondary cataract was noted in 31% of cases. PMID- 1886353 TI - [Astigmatism in cataract surgery. Retrospective study of 1,304 cases]. AB - We performed a retrospective computerized study of 1304 consecutive cataract extractions, of which 251 were intracapsular and 1053 extracapsular. The analysis of surgically induced astigmatism after a mean follow-up of 22.8 months involved 639 cases. Operations were performed by two experienced surgeons using a similar and standardized technique; however the location of the incision varied without selecting patients: 391 were corneal, 248 limbal. We found that corneal incision gives significantly more against-the-rule astigmatism (average -0.61 dptr) than limbal incision (average -0.32 dptr). The suture induced astigmatism has no determining effect on the final astigmatism (correlation coefficient = 0.011). Selective suture cutting is an interesting technique for an individual dosage of the amount of final astigmatism. PMID- 1886354 TI - [Is there an ideal surgical time for retinitis pigmentosa patients with cataract?]. AB - According to the literature, a fully developed cataract should be removed generally when the macula is intact. However, patients with a slowly progressing retinal disease find themselves in a particularly difficult situation. In this clinical, retrospective study, 24 retinitis-pigmentosa (RP) patients after cataract surgery were asked whether they recommend cataract surgery early or late in the course of the development of the retinal disease. A correlation was found between the answers to this question and the time elapsed between each patient's own operation and his interview. Three preference groups resulted through statistical evaluation: 1) those who recommend an early operation (n = 8), 2) those who recommend a late operation (n = 8), and 3) those who were undecided (n = 8). All patients had been operated at the same time following the RP onset and cataract diagnosis. Those patients who preferred a late operation had been questioned in this regard considerably later after their own operation than those who preferred an early operation. In other words, the preference for an early or late operation depended on how much prior to the questioning the patient's own operation had been conducted. The RP patient, quite disease conscious, has an exact conception of the ideal time of cataract operation in RP patients in general, but this does not always coincide with the opinion of his physician. It is considerably more necessary to consider the individual situation of the RP patient than that of normal cataract patients. PMID- 1886355 TI - [Value of the ophthalmologic examination in diagnosing patients with Anderson Fabry disease and in heterozygote detection]. AB - A 45-year-old man with Fabry's disease is presented. 27 relatives are examined. Among the different examinations (serum activity of alpha-galactosidase, urinary excretion of trihexosyl ceramide, renal function, ocular examination) ocular examination remains the easiest and cheapest test for detection of heterozygotes. The ocular manifestations of this enzymatic defect are reviewed. PMID- 1886356 TI - [Prevention of ocular complications of herpes zoster ophthalmicus by adequate treatment with acyclovir]. AB - We compared the frequency of severe ocular complications secondary to Herpes Zoster Ophthalmicus (HZO) in 232 patients. They were divided into three groups: 1) patients without treatment (n = 164); 2) patients treated adequately (n = 48) with acyclovir (ACV; 5 x 800 mg/d orally and ophthalmic ointment 5 x /d for a minimum of 7 days, given within three days after skin eruption); and, 3) patients treated inadequately (n = 20) with ACV (only topical treatment, insufficient doses, interrupted treatment, delayed treatment). Patients with no treatment or with inadequate treatments showed the same frequency of severe ocular complications (21% (34/164) and 25% (5/20), respectively). In contrast, when adequate treatment of ACV was given complications occurred in only 4% (2/48) of cases. This study emphasizes the need for prompt (within three days after skin eruption) and adequate (5 x 800 mg/d for at least 7 days) treatment of ACV to prevent the severe complications of HZO. PMID- 1886358 TI - [Uveal melanomas and vitreous hemorrhage. Diagnosis and treatment]. AB - In choroidal melanoma vitreous hemorrhage can occur as initial event or as complication of conservative therapy. To understand better these relations, four groups of cases were examined: 1.) 126 choroidal melanomas which were treated conservatively with Cobalt 60 applicator from 1969 till 1984. 2.) 715 choroidal melanomas which have been treated with proton-beam from 1984 to 1989. 3.) 7 tumors or pseudotumors for which for diagnostic purposes a phosphorus 32 test was necessary. 4.) 9 choroid melanomas which had conservative treatment and where vitrectomy was realized. The multifactorial analysis gave the following results: in vitreous hemorrhages occurring before treatment the thickness of the tumor represents the significant factor. In vitreous hemorrhages which occur after conservative treatment there is in the group of cobalt applicators important irradiation of the disc, as well as the thickness of the tumor and the age of the patient in the group with proton-beam irradiation. Vitreous bleeding occurring before or after therapy does not influence the vital prognosis in a negative way. We present here a therapeutic concept in cases of vitreous bleeding in choroid melanoma which is based both on our experience and on the indications of literature. PMID- 1886357 TI - [Ocular melanocytosis, oculodermal melanocytosis and choroid melanomas]. AB - Among 837 cases of choroidal melanomas treated conservatively, 22 cases (2.69%) presented an ocular or oculodermal melanocytosis. This incidence is compared with the data of the literature. The role of melanocytosis on tumors' parameters and vital prognosis is studied. PMID- 1886359 TI - [Retinal vascular occlusion in a young patient with hemostatic abnormalities]. AB - Retinal vascular occlusion (RVO) in the young patient without vascular parietal disease have been encountered in different pathologic states, coagulopathy being frequent. We started a prospective study in Geneva to find out the hypercoagulable states responsible for RVO. We give suggestions to the paraclinical investigations to perform. We discuss the primary and secondary hypercoagulable states in the light of two patients who had coagulation abnormalities. PMID- 1886360 TI - [Occlusion of a cilioretinal artery associated with occlusion of the central retinal vein]. AB - Cilioretinal artery occlusion (CLRAO) may be occasionally associated with central retinal vein occlusion (CRVO). This combined retinal vascular pathology is described in 5 patients. In this clinical setting the vulnerability of cilioretinal vessels can be explained by the difference in regulatory mechanisms between choroidal and retinal blood flow. The type of CRVO may predict whether the CLRAO is primary or secondary to the CRVO. PMID- 1886361 TI - [Macular neuroretinopathy]. AB - The isolated presumably inflammatory involvement mostly acute and unilateral of the photoreceptor layer of the retina, in the macular region, has been described as clinical entity: macular neuroretinopathy. Three cases are presented. Its evolution, ophthalmoscopic appearance (cuneiform tear drop), negative angiofluorography, normal electroophthalmography, differentiates neuroretinopathy from cystoid edema (CME), retinoschisis, acute macular multifocal placoid pigmentepitheliopathy, pigmentepitheliitis, and "Multiple evanescent white dot syndrome" (MEWDS). Visual acuity is mildly decreased but its recovery is poor even after a long period of time. Secondarily the pigmentepithelium may be involved. MEWDS is characterised by a primary fruste involvement of the pigmentepithelial layer simultaneously with a secondary involvement of the choriocapillaris, and possibly photoreceptor layer. PMID- 1886362 TI - [Short- and intermediate-term angular results of Cuppers retro-equatorial myopexy, with or without additional simultaneous recession]. AB - 79 variable esotropias underwent bilateral "Fadenoperations". In the first group, the posterior fixation has been performed alone. In the second series, conventional symmetrical recessions of the medial recti have been performed during the same procedure. Two further additional weakening techniques are compared in the last group: anterior medial tenotomies and the so-called "stretch effect". Concomittant recessions considerably enforced the amount of angle reduction for distance and near without affecting precision, predictibility and stability of the results. Tenotomies and stretching procedures were followed by inconstant results. PMID- 1886364 TI - [Lower eyelid extension-plasty in patients with ptosis in chronic progressive external ophthalmoplegia]. AB - Correction of ptosis in patients with chronic progressive ophthalmoplegia is problematic because the ptosis enlarges the palpebral fissure and aggravates the lagophthalmos. Additional lifting of the lower lids, which are often retracted, therefore seems advisable. Experience with various lower lid elongation techniques is reported. PMID- 1886363 TI - [Use of autologous ear cartilage in eyelid surgery]. AB - Autologous ear cartilage is relatively easy to procure in suitable form and sufficient quantity. At the donor site, there are, as a rule, no complications to be expected. Autologous ear cartilage without conjunctival coverage is of good use for replacing and lengthening the inner layer of an eyelid, not only to reconstruct large eyelid-defects, but also to give additional support and length. The cartilage graft will grow on well, provided the wound is well vascularized. This must not be expected with scarring or poor blood perfusion. The brittleness of the cartilage demands an adapted technique. Precautions to protect the cornea and to prevent adhesions in the fornix are to be taken. PMID- 1886365 TI - [Theoretical and practical vision quality with diffractive-multifocal lenses]. AB - I investigated the discrimination of objects with diffractive bifocal contactlenses, when objects in different distances are presented simultaneously. Computer assisted considerations suggested an impairment of discrimination as compared to monofocal correction for far as well as for near. The theoretical loss of image information has been shown to occur also in a visual test with steric arrangement of object points. However, the experiments suggested, that this kinds of visual quality impairment does not play a dominant role in the qualification of diffractive bifocals, since a rather sophisticated procedure was needed to demonstrate the expected effect. PMID- 1886366 TI - [Tyndallometry of the anterior chamber with the Kowa FC-100 Laser FLare-Cell Meter]. AB - The laser flare-cell meter measures the scattered light intensity of a He-Ne laser in the aqueous of the anterior chamber. It allows a reliable quantitative determination of the flare and the number of cells in the aqueous humor. The aqueous flare intensities are significantly decreased by short-acting mydriatic agents such as 0.5% tropicamide and phenylephrine. Diurnal variations and an increase of the aqueous flare with increasing age were demonstrated. PMID- 1886367 TI - [Behavior of the other eye in measuring fixation disparity]. AB - In the subjective measurement of FD, the proband fuses contours presented in the peripheral macular areas of both eyes ('fusion lock'). The position of both eyes relative to each other is monitored by means of two haploscopically seen vertical lines presented in the central visual field, one above and one below a binocularly seen horizontal line. The subject is instructed to shift one of the vertical lines horizontally until the two are aligned, while fixating their intersection with the horizontal line. It has recently been questioned whether the foveolae really are pointed at the perceived intersection. To investigate this matter, we registered the position of one eye while intermittently covering the fellow eye, while the subject maintained fixation of the intersection. We found slight differences in monocular eye position depending on the presence or absence of fusion in the macular periphery, confirming earlier findings in part. These differences were more pronounced in the nondominant eye. PMID- 1886368 TI - [Regulation of PO2 in the area of the optic papilla of the minipig in hyperoxia]. AB - PO2 measurements using a double barrelled recess type microelectrodes were measured in the optic nerve head of miniature pigs in normoxia and hyperoxia. Although periarteriolar PO2 increased markedly during systemic hyperoxia (100% oxygen breathing), the intervascular PO2 remained stable under hyperoxia. These results suggest a regulation of the tissue PO2 of the optic nerve head, as the retina does, at constant values during hyperoxia. PMID- 1886369 TI - [The effect of glucose on rod function in the isolated, perfused cat eye]. AB - Effects of changing glucose concentration on light-evoked, rod-matched electrophysiological responses were studied in isolated, arterially perfused cat eyes. 1. changes in glucose concentration in the perfusate induced remarkable effects in the electrical responses of retinal pigment epithelium neural retina, and optic nerve. 2. The ERG b-wave and the optic nerve response (ONR) were enhanced when glucose concentrations were increased above the standard level (5.5 mM), and were less than normal after termination of the increase in glucose, prior to recovery. 3. Decreasing glucose from the standard led to attenuation of b-wave and ONR. Both responses recovered completely upon returning to 5.5 mM glucose 4. When the control perfusate contained higher glucose concentrations (8 10 mM), additional glucose failed to elicit significant effects on the b-wave and on the ONR. 5. Increasing glucose induced a small transient decrease in standing potential, followed by a marked and maintained increase. Decreasing glucose induced changes of similar magnitude but opposite polarity. 6. Supply of glucose to mammalian retina in vitro is crucial for optimal sensitivity as shown in rod matched signals from the perfused cat retina. PMID- 1886370 TI - [Immunolocalization of fodrin in the retina of vertebrates]. AB - Fodrin, a member of the spectrin family, is abundantly found in brain and lens. Based on its often observed peripheral cellular distribution, it is generally believed that fodrin - like other spectrins - participates in the linkage of membrane components to cytoskeletal elements providing their anchorage to distinct, highly specialized membrane regions. To investigate the role of fodrin in the vertebrate (amphibian) retina, we have produced polyclonal antibodies in rabbits against fodrin purified from veal lens. The distribution of fodrin within the retina of Xenopus and Rana has been assessed by indirect immunofluorescence on cryostat sections and on isolated epithelial cells. In general, the staining pattern reflects the structural and functional polarity of the retinal layers. Fodrin is found in axons, dendrites and synapses of neurons, in the inner segment of photoreceptors, and as a peripheral ring of the epithelial cells. This study represents the first step of an investigation on the development and differentiation of specific, fodrin-containing membrane regions in the amphibian retina. PMID- 1886371 TI - [Ocular vasospasm. 1: Functional circulatory disorders in the visual system, a working hypothesis]. AB - Patients with normal-tension-glaucoma and with visual field defects of non-known origin, often suffer from mild vasospasm in the fingers. The observation often be provocated by coldness or emotional stress and that these defects can very often be reduced by a treatment of the vasospasm led to the hypothesis that a functional dysregulation of the circulation in the visual system might occur. PMID- 1886372 TI - [Ocular vasospasm. 2: Diagnosis of vasospastic syndrome using nailfold capillary videomicroscopy]. AB - Nailfold capillary videomicroscopy provides a very useful method to verify vasospastic disorders in ophthalmic patients. Capillary videomicroscopy at the nailfold in connection with a local cold exposure test are presented as a method with clinical applicability in vasospastic disease. This method allows not only differential diagnosis of Raynaud's phenomenon and evaluation of follow up but also to achieve pharmacological tests with different drugs which possess a specific action at the microvascular bed. PMID- 1886373 TI - [Ocular vasospasm. 3: Contribution of choroid angiography]. AB - In patients with ocular vasospasm a disturbance of papillary blood flow is discussed. The peripapillary choroidal circulation is of great interest because it supplies the papillary circulation. The Indocyanine green video-fluorescence angiography provides evaluation of choroidal blood-flow. In some cases of ocular vasospasm disturbance of choroidal blood flow could be found. Examples of these cases are demonstrated. PMID- 1886374 TI - [Ocular vasospasm. 4: Clinical examples]. AB - The presumed ocular vasospasms provoke a variety of symptoms. Out of the large spectrum, two typical cases are described. The first case is a patient that developed visual field defect under psychological stress conditions. A drug therapy relieved the patient from the symptoms. The second case is a patient with a normal-tension-glaucoma. The treatment of the vasospasm improved the visual field markedly. PMID- 1886376 TI - [Cryocoagulation of eyelid basaliomas. Limits of the technique]. PMID- 1886375 TI - [Lausanne study of retinoblastoma, 1986-90: deletion of esterase D locus in a collective of 128 patients]. AB - Activity and phenotype of red blood cell esterase D were systematically determined in a population of 128 retinoblastoma patients from 99 families and compared to 158 controls, in order to detect a chromosome 13q14 deletion. Among these patients 12 were healthy carriers and 116 affected carriers of a mutant allele of the retinoblastoma susceptibility gene (110 retinoblastoma, 5 retinoma, 1 phtisis bulbi). 4 patients were found to have decreased ESD levels in connection with 13q14 deletion which was confirmed by chromosome analysis. The data presented here suggest that ESD quantification has a high specificity and sensitivity for the detection of homogenous chromosome 13 deletions in retinoblastoma patients. PMID- 1886377 TI - [Healed (?) amoebic keratitis]. AB - Acanthamoeba keratitis was seen in two contact-lens wearers. In both cases, this finding was verified by microbiological examination of conjunctival swabs and of the lens solution. One patient had perforating keratoplasty. While neither vital amoebae nor cysts could be detected in the host corneal explant, immunohistochemical examination revealed fluorescence-positive fragments which probably correspond to incomplete cycstic walls. PMID- 1886378 TI - [Oculocerebral malignant non-Hodgkin lymphoma. A report of 5 cases]. AB - Five patients, age 35 to 77, with histologically proven malignent ocular non Hodgkin's lymphoma (previously known as reticulum cell sarkoma) are presented. The clinical ocular findings (vitreous infiltrates, retinal infiltrates, anterior uveitis) were initially misinterpreted as "panuveitis". The usual antiinflammatory therapie a temporary diminution of the "uveitis" could be observed. Four cases showed a histologically proven CNS involvement. All the patients (except the one in whom the correct diagnosis was made post mortem) received cerebral radiation therapie, including the eyes. Under the radiation therapy the ocular findings disappeared within a few weeks. The longtime prognosis for the eye and quoad vitam is unfortunately not promissing. PMID- 1886379 TI - [Vitrectomy in secondary complications caused by intraocular foreign body]. AB - Endophthalmitis and reduced vision as late complications of penetrating ocular injuries cause specific diagnostic problems. A persisting endopthalmitis may be caused by unnoticed organic foreign bodies (f.b.) like lashes or a splinter of glas. Endophthalmitis recurring months or years after a perforating injury indicates the possibility of a spontaneous mobilization of a f.b. Vitrectomy and removal of the f.b. is the therapy of choice in either situation. Five typical cases are presented: lashes encapsulated in the ciliary body following a limbal perforation; an intraretinal incarceration of a lash of unknown history; spontaneous dislocation of a glas splinter from the ciliary body into the anterior chamber; delayed spontaneous translocation of a 10 x 11 mm metallic f.b. from tenon's space transsclerally into the subretinal space leading to endophthalmitis one year after a severe perforating injury; secondary mobilization of an intraretinal piece of stone during a posterior hyaloid detachment. In each case, vitrectomy was performed and the f.b. removed via pars plana. Secondary surgery for retinal detachment or PVR was necessary in 2 cases. The final visual acuity was 20/20 in 3 cases and 10/20 or better in 2 cases. PMID- 1886380 TI - [46-year follow up of malignant transformation of choroid nevus with vascularized surface drusen]. AB - The unusual long and atypical clinical course of a prominent black choroidal tumor is presented. It was stationary for decades and became symptomatic for many years. The histologic findings post mortem showed a choroidal nervus with focal malignant change. Its symptoms were obviously caused by subretinal vascularized soft drusen. Only two histologic descriptions of this little-known change over choroidal nevi and two of histologically proven malignant transformations of choroidal nevi are published up to now. PMID- 1886381 TI - [Case report of Laurence-Moon-Bardet-Biedl syndrome]. AB - We report a case of Laurence-Moon-Bardet-Biedl Syndrome with all five recognised features: tapetoretinal dystrophy, polydactily, obesity, mental retardation and hypogonadism. Nevertheless the correct diagnosis was delayed due to the fact, that the patient has a macular dystrophy (instead of a pigmentary retinopathy). He had an operation of the polydactily during childhood. This was not revealed at first. The case underlines the importance of an exact anamnesis of the parents. PMID- 1886382 TI - [Uveitis after Yersinia enterocolitica infection]. AB - Yersiniosis is a food-born infection. It may cause an acute enterocolitis and trigger an anterior uveitis. We report a case of bilateral panuveitis with chorioretinitis - thus with the involvement of anterior and posterior uvea. Because the agglutination titer against the Yersinia enterocolitica type 3 was increased, we consider it as the most probable etiology of the panuveitis. A serological test for Yersinia should be done in patients with uveitis, who consume food from various sources e.g. tourists or with diarrhea in anamnesis. PMID- 1886383 TI - [Multiple evanescent white dot syndrome]. AB - MEWDS is a benign acquired disorder of the retinal pigment epithelium of unknown etiology which has been first described in 1984. Actually more than 50 cases have been reported worldwide but only 5 cases from Europe. We report 10 other cases of MEWDS, seen in the past 5 years. Their clinical presentation, perimetric and electroretinographic results, as well as their differential diagnosis will be reported. PMID- 1886384 TI - [Valsalva's maneuver: not always benign]. AB - Five cases are being discussed here, where an apparently harmless Valsalva manoeuvre caused different clinical manifestations in the eyes: a large central preretinal hemorrhage, diffuse retinal hemorrhages, a Purtscher retinopathy and a blindness associated with a haematoma of the upper and lower lid of the right eye, probably caused by bleeding in the sheeths of the optic nerve. It is important to note that a Valsalva manoeuvre can cause different manifestations in the eye, apart from the known small premacular haemorrhage. Since the Valsalva manoeuvre is a common phenomenon, one should keep it in mind when observing unclear ocular findings. PMID- 1886385 TI - [Diagnosis of optic neuropathy in endocrine orbitopathy]. AB - By presenting the case of a patient with Graves-disease, different methods that permit detection of optic nerve compression are discussed. Beside reduced visual acuity and pathological visual fields, measurement of episcleral venous pressure, pathological visually-evoked potentials (VEP) and enlarged extraocular muscels (detected by CT and MRI) give good additional evidence of optic nerve compression in Graves-disease. PMID- 1886386 TI - [Is vision measurement by vision tables accurate?]. AB - We observed that often visual tables are different, so that one patient can be shown to have different visual acuities. We show the more important characteristics that a standardized visual table should have. PMID- 1886387 TI - [Results of full binocular correction versus conventional methods]. AB - 163 patients suffering from different serious troubles were treated with binocular full correction (BFC) i.e. examination by Polatest and prismatic correction. Before, they all had seen other ophthalmologists. The former diagnose and therapy are listed and compared with those of the author. RESULTS: After a 2 2/3 years average follow-up period 68% of the patients were complaintless, 23% felt better. All patients reached at least binocular single vision, although initially 13% had no binocular vision and 1% complained about diplopia. 70% got ideal binocular vision (initially 0%). In the beginning 50 patients suffered from reduced visual acuity. It improved in all cases with differences of v.a. from 2 4/10 to 10/10. From the shown results the author concludes that conventional binocular diagnostic and therapeutic methods do no longer meet the state of the art. It is postulated that BFC should be accepted by school-medicine and that ophthalmologists and orthoptists should be trained in BFC. Only in this way ophthalmologists may fulfil their task to free patients from the many complaints caused by binocular troubles. The used terminology about BFC is explained in the appendix. PMID- 1886389 TI - [Computer as replacement for the current medical record? Introduction of a pilot project of the St. Gallen ophthalmology clinic]. AB - Computerized data processing is more and more used in hospitals and medical offices. There are no doubts about the usefulness of a computer for administrative tasks. At our Dept. of Ophthalmology we started a pilot project to enter the medical records into the computer. The pros and cons of such an information system are discussed. Entering medical records into the computer did not prove to be definite advantage for the physician. PMID- 1886388 TI - [Usefulness of the Laser FLare Cell Meter (LFCM, Kowa FC-1000) for evaluating inflammation of the anterior chamber in clinical practice]. AB - The Laser Flare Cell Meter (LFCM, Kowa FC-1000), an instrument measuring aqueous flare and cells in a quantitative, objective and non-invasive way, has been mainly used so far to measure inflammation in clinical and experimental research. In the light of some illustrative examples, its practical clinical usefulness is presented; the LFCM was found to be specially helpful in 3 types of situations. 1. In acute anterior uveitis (AAU) patients, precise LFCM monitoring of inflammation made it possible to avoid excessive corticosteroid therapy, mainly by more rapid and controlled tapering at the end of an inflammatory episode, so possibly minimizing steroid side effects in a group of patients prone to numerous uveitis recurrences. In a steroid-responder patient it allowed successful treatment of a flare-up of AAU with a combination of systemic and topical diclofenac (Voltaren), a potent nonsteroidal antiinflammatory drug. 2. LFCM monitoring of inflammation in patients undergoing laser treatments allowed optimal adjustment of antiinflammatory therapy. Diclofenac drops (Voltarene Ophta), were sufficient to treat inflammation in all patients, undergoing Nd-YAG laser posterior capsulotomy or Argon laser trabeculoplasty. 3. In patients with acyclovir treated herpes simplex or herpes zoster uveitis corticosteroid treatment should be avoided whenever possible, because of the tendency to develop steroid dependency. LFCM monitoring of this group of patients gave a precise evolutionary pattern of inflammation and permitted to avoid steroid treatment in many patients. PMID- 1886390 TI - [A new soft contact lens of 2-component silicone]. AB - Silicon lenses, noted for their flexible elasticity, were submitted for patent registration prior to HEMA lenses, and before practical experience was available. Favorable clinical trials remained undone for a long time. After preclinical tests with additively moistened silicons and a new hydrophilic coating, clinical evaluation was conducted in accordance with the guidelines of the american health authorities (FDA). Contact-lens centers in Germany and Switzerland participated in these tests. Statistical analysis was done on the results from 233 test persons. PMID- 1886391 TI - [Practical experiences in conversion to the wide angle observation systems for vitreous surgery BIOM, SDI, VPF]. AB - The wide-angle observation system for vitreous surgery introduced by Spitznas und Reiner has the following advantages: Wide angle of view. Large depth of field. Good view to the periphery even with narrow pupil. Easy gas fluid exchange in a phacic eye. Free mobility of the eye when working in the periphery. Changing from the conventional vitrectomy lens system to the BIOM an experienced surgeon is familiar with the new system in a very short time. PMID- 1886392 TI - [Low vision counseling with children--exemplified by a sibling pair with congenital nystagmus]. AB - We describe several visual aids that were given to two visually impaired children from our low-vision service of St. Gallen Eye Hospital. Visual aids alone do not guarantee success as collaboration between the ophthalmologist, the low-vision trainer, the child and his parents is fundamental. PMID- 1886393 TI - [Diabetic retinopathy: a new challenge of the year 2000]. AB - New programs for the prevention of blindness caused by diabetic retinopathy have been elaborated in different countries. The author analyses the results of a survey conducted in Switzerland in 5 University Ophthalmology clinics and in 9 regional centres, reviewing the ocular examinations and treatments applied to diabetic patients. A common attitude towards this disease is suggested. PMID- 1886394 TI - [Value of the RPM safety index in retinopathy of prematurity]. AB - The safety-index (S-index): S = log birth weight (kg) + gestational age (weeks)/oxygen therapy (days) combines the three main risk factors for a development of ROP. Only in very immature children which had a long time oxygen therapy (and therefore a low S-index) one finds severe stages of ROP. In our study, we correlated retrospectively ROP stages versus S-index in 261 children. The results confirm that children with S-index greater than 1 never had a severe ROP (that means, stage 3 and more, which need treatment). Therefore, the 2/3 of all newborn infants at risk with an S-index greater than 1 need only minimal ophthalmological controls. PMID- 1886395 TI - [Assessing accidental damage to the integrity of the eye with preexisting damage]. AB - According to the insurance law, compensation for damage of integrity has to be realized only in cases of accident caused damage of integrity. In cases of preexisting damage on the affected eye the evaluation is simple: Total damage minus non accidental cause integrity damage is equal to accident caused damage of integrity. More difficult is the evaluation in cases of preexisting damage on the partner eye. According to the visual function of the non affected eye (first eye) the basic value of the accident eye (second eye) amounts in case of total loss between 30 and 70%. Values in between in cases of partial damages are explained by means of a three-dimensional graphic. PMID- 1886396 TI - ["ORO" (Opportunity Recycling in Ophthalmology) Project '90: Collection of usable ophthalmologic equipment for the Dr. Betrix Clinic for Women/Cameroon]. AB - The developmental-assistance entreprise, "Opportunity Recycling in Ophthalmology (ORO)", recycles used but still usable equipment in Ophthalmology and material from the storage-rooms of eye clinics and private ophthalmological practices to responsible recipients in the Third World. ORO was found in 1977 and was given "Honorable Mention" from "Prix Rolex a l'esprit d'entreprise" in 1978. The current project consists of locating, reconditioning, and organizing the transport of material for the Dr. A.-F. Betrix Clinic in Kusseri, in the most northern province/Cameroon. As always, ORO is here, too, dependent on the generosity of clinics and private ophthalmologists. PMID- 1886397 TI - [The antibaby pill as a risk factor for thrombosis: are the molecular mechanisms known?]. AB - Oral contraceptives are being associated with an increased risk of thrombosis. Measurements of clotting factor abnormalities in plasma can not predict the individual risk of thrombosis, nor can they explain the pathophysiology of the clinically known association of thrombosis and oral contraceptives. Research conducted over the last 10 years points to the important role of endothelial cells, fibroblasts and monocytes in the regulation of the initiation of coagulation. Hence we propose, that the molecular mechanism of oral contraceptive associated thrombosis can only be elucidated by studies looking at the effect of these drugs on cellular elements involved in coagulation. Measurements of plasmatic coagulation factors can not indicate safety or risk for a patient taking any of the multiple drugs available. PMID- 1886398 TI - Serum osteocalcin levels in primary hyperparathyroidism. AB - The serum levels of osteocalcin, a 49-amino-acid bone-matrix protein, have been found to be a specific biochemical parameter of bone formation. The aim of our study was to compare the sensitivity of serum osteocalcin levels with that of alkaline phosphatase in the evaluation of patients with primary hyperparathyroidism. In 40 patients with biochemically and histologically confirmed primary hyperparathyroidism, the serum levels of osteocalcin, intact parathyroid hormone, alkaline phosphatase, calcium, phosphorus, and creatinine were determined preoperatively. The serum levels of osteocalcin were elevated in 22 patients (55%), whereas the serum levels of alkaline phosphatase were increased in 18 patients (45%). In 10 patients (25%) the serum levels of osteocalcin, but not those of alkaline phosphatase, were increased, whereas in six patients the activity of alkaline phosphatase was high, but the serum osteocalcin levels were normal. When the biochemical data of the patients with increased serum osteocalcin levels were compared with those of the patients with serum osteocalcin levels within the normal range, the serum levels of intact parathyroid hormone and alkaline phosphatase were significantly increased in the group of patients with elevated serum osteocalcin levels. Our data indicate that serum osteocalcin levels might be a clinically useful additional parameter in the evaluation of patients with primary hyperparathyroidism. PMID- 1886399 TI - [Neurologic and psychiatric complications after heart surgery]. AB - In 63 patients undergoing heart operations with extracorporeal circulation (47 males, 16 females, mean age 54 years; coronary artery bypass in 38 cases, valvular surgery in the rest) postoperative neurological and psychiatric complications were evaluated. 18 patients (29%) had no complications, whereas 35 patients (56%) showed minor or transient neurological symptoms, and 9 patients (14%) exhibited severe symptoms. Nine of the patients had slight psychiatric disturbances (affective disturbances, disorientation). No correlation was found between risk factors (age, nicotine abuse, hypertension, hypercholesteremia, neurologic and cardiac history), intraoperative parameters (duration of extracorporeal bypass, aortic clamp time, deviation of mean arterial pressure), postoperative parameters (internal complications) and the complication rate. Therefore no predisposing factors could be identified. PMID- 1886400 TI - [Fatal infection after splenectomy despite reimplantation of splenic tissue]. AB - A fatal case of a postsplenectomy sepsis is presented which occurred in a 5-year old boy 11 month following splenectomy due to trauma and reimplantation of splenic tissue. The patient died 4 h after admission to the hospital. The post mortem revealed an encephalitis and a sepsis although splenic regenerates were found in the omentum pouch. Our report increases the number of cases described to date in the literature to a total of 18. Autologous reimplantation of splenic tissue does not offer complete protection against over-whelming infection. PMID- 1886401 TI - Strategy for the screening of tetrahydrobiopterin deficiency among hyperphenylalaninaemic patients: 15-years experience. AB - Tetrahydrobiopterin deficiency in hyperphenylalaninaemic babies has to be rapidly recognized since the disease requires a specific treatment. Based on 15 years experience, we report on the evolution of a strategy for the detection of such patients. A total of 913 hyperphenylalaninaemic patients have been studied and 15 tetrahydrobiopterin deficiencies have been detected or confirmed. DHPR assay in dried blood samples and pteridine measurement in urine collected on filter paper combine convenient sampling and reliable tests for systematic investigation of hyperphenylalaninaemic patients for cofactor deficiency. PMID- 1886402 TI - First trimester diagnosis of inherited metabolic disease: experience in the UK. AB - Experience with first trimester diagnosis of inherited metabolic disease is still limited. In this report, data are collected from four major centres in the UK which provide a prenatal diagnosis service based on specific enzyme or gene product assay. The data were presented at a workshop on 'First Trimester Diagnosis of Inherited Metabolic Disease' held at the Institute of Child Health, London, on 21st June 1990. Approximately 100 different metabolic diseases can now be diagnosed in the first trimester, but because of the rarity of many of the disorders, experience of positive diagnoses, based on enzyme deficiency in fresh chorionic villus samples (CVS), cultured villus cells or early amniocentesis samples, is likely to be limited. It is, however, important that these results are reported and similarly that any problems which arise are fully documented. PMID- 1886403 TI - 3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) lyase deficiency in Saudi Arabia. AB - Deficiency of 3-hydroxy-3-methylglutaryl-CoA lyase has been studied in 11 Saudi infants. The diagnosis was established by the measurement of enzyme activity in lymphocytes, in fibroblasts and, in seven patients, by the gas chromatography/mass spectrometer pattern of excreted organic acids in the urine. In seven infants the disease caused a devastating acidotic attack within the first day of life, while in two the crisis occurred by the third day of life. In two infants from one family the disease appeared later in infancy. The clinical presentation of an acidotic attack is lethargy, hyperpnoea, tachypnoea and seizures, either at birth (two infants), following first feeding (in five infants), or following vomiting or refusal of food in later infancy. The acidotic attacks recurred later in life following minor illness or refusal to eat. The acidosis of this enzyme deficiency progresses rapidly, leading to cardiopulmonary arrest and death within hours of onset unless treated promptly. In four surviving infants diagnosed and treated early, development is normal. Magnetic resonance and computerized tomography brain scans in these infants, however, show white matter lesions and mild atrophy. PMID- 1886404 TI - Phenotypic variability and abnormal type I collagen unstable at body temperature in a family with mild dominant osteogenesis imperfecta. AB - Autosomal dominant inheritance of a mild form of osteogenesis imperfecta (osteogenesis imperfecta type I) with different phenotypic expression was found in a family. Phenotypic expression was different for the affected mother and son, in the presence of the same biochemical results. Dermal fibroblast cultures synthesized normal and mutant type I collagen alpha chains. Collagen heterotrimers containing abnormal chains were overmodified along the entire triple helical domain and showed an unusually low denaturation temperature, so far found only in lethal cases. The mild phenotype in the family is probably due to the fact that abnormal type I collagen molecules are more likely to be degraded than utilized in the extracellular matrix. PMID- 1886405 TI - The pathogenesis of the Lesch-Nyhan syndrome: ATP use is positively related to hypoxanthine supply to hypoxanthine guanine phosphoribosyltransferase. AB - In order to explain features of severe hypoxanthine guanine phosphoribosyltransferase (HPRT) deficiency, the Lesch-Nyhan syndrome, a continuous supply of substrate, hypoxanthine, for the enzyme must be generated. This supply must be increased in association with increased ATP turnover. We have shown that ATP turnover continuously supplies hypoxanthine for recycling by the enzyme HPRT and that this supply increases curvilinearly with increasing ATP turnover. The effects of increasing exercise on ATP turnover were examined using a Latin square experimental design. The outputs of hypoxanthine, xanthine, urate and creatinine were measured. The data were then examined statistically. PMID- 1886406 TI - 2-Deoxy-D-glucose uptake and fatty acid content in fibroblast cultures from children with syndromic paucity of interlobular bile ducts (Alagille syndrome). AB - 2-Deoxy-D-glucose (2-DOG) uptake was studied in skin fibroblast cultures from control children and children with Alagille syndrome or syndromic paucity of interlobular bile ducts (PILBD). No significant differences in uptake were observed between patients and controls. However, as the scatter of the results was larger in the fibroblasts from patients, we attempted to establish for these patients a relationship between 2-DOG uptake and some biochemical parameters. We observed an inverse relationship between this uptake and the levels of plasma cholesterol and phospholipids (r = -0.85). Compared to controls, 2-DOG uptake was significantly lower in cultures from patients who had very high levels of cholesterol (P2 group), but not in cultures from patients with moderately increased levels of cholesterol (P1 group). The level of total cellular cholesterol in cultured cells from the P1 and P2 groups was not significantly different from the control level, but we found marked differences between the concentrations of fatty acids. In the cultures from patients (especially the P2 group), we observed a significant increase in total fatty acids; among the saturated fatty acids, this increase chiefly concerned the 18:0 (14%) and among the polyunsaturated the n - 3 fatty acids (55%). The high concentrations of 20:5, 22:5 and 22:6, which enhance membrane fluidity, might explain the decrease in 2 DOG uptake found in the cultures from patients (P2 group) with PILBD. The nature of these abnormalities might be connected with the genetic origin of Alagille syndrome. PMID- 1886407 TI - Thyroid structure and function in bovine beta-mannosidosis. AB - In bovine beta-mannosidosis, the thyroid in the affected newborn shows marked cytoplasmic vacuolation. There is an associated reduction in the serum concentrations of thyroxine and tri-iodothyronine. PMID- 1886408 TI - Fruits and vegetables are a source of galactose: implications in planning the diets of patients with galactosaemia. AB - It has become apparent that removing dairy products from the diets of patients with galactosaemia does not sufficiently diminish the deleterious signs. We have determined the amount of soluble monomeric galactose in 45 fruits and vegetables using capillary gas chromatography and selective ion monitoring. Galactose contents ranged from less than 0.1 mg per 100 g of tissue in artichoke, mushroom, olive, and peanut to 35.4 mg per 100 g in persimmon. Fruits and vegetables with over 10 mg per 100 g included date, papaya, bell pepper, tomato and watermelon. These results will provide important data for planning the diets of patients with galactosaemia. PMID- 1886409 TI - Mild form of methylmalonic aciduria misdiagnosed as propionic acidaemia during a ketotic crisis. PMID- 1886410 TI - Canavan disease: findings in four new cases. PMID- 1886411 TI - Hepatic phosphorylase b kinase deficiency with normal enzyme activity in leukocytes and erythrocytes. PMID- 1886412 TI - Bone marrow transplantation in Lesch-Nyhan disease. PMID- 1886414 TI - Maintenance of CNS tissues in vitro for subsequent pharmacologic evaluation: a simple and inexpensive superfusion chamber. AB - A new simple, inexpensive holding chamber is described for maintaining brain slices in a viable condition for long periods of time. The advantages of its superfusion-type operation and application of this chamber to in vitro electrophysiologic studies of the pharmacologic action of serotonin in the midbrain dorsal raphe nucleus are discussed. PMID- 1886413 TI - Placental transfer of theophylline during in situ perfusion in the rabbit. AB - Many physiological changes take place during pregnancy, and the disposition profile of endogenous and exogenous compounds may change, too. Thus knowledge of the disposition pattern of a compound may be useful in relation to its therapeutic effect(s) and its potential toxicity on the fetus and the newborn. Because the amount of a compound received by the fetus is a product of placental transfer rate, and available maternal amount, and because it is difficult to control and evaluate the factors that may affect such a transfer in women, we set up an in situ perfused placental model in the rabbit. The reliability of the model was borne out by comparing the placental transfer of theophylline with antipyrine, a commonly used marker of placental exchange, at steady state after a two-step infusion at mean arterial plasma concentrations of 8 and 5 mg/L, respectively for theophylline and antipyrine. The rabbit placenta was perfused in situ with a modified Earle's buffer at a 1-mL/min flow rate. During perfusion, maternal plasma, placental perfusate, biochemical parameters, gas exchange, body temperature, and electrocardiogram were carefully monitored. The maternal plasma and perfusate drug concentrations over time were fitted by appropriate models and kinetic parameters were calculated. Umbilical vein/maternal artery concentration ratios reached equilibrium soon after the loading infusion was stopped for both drugs. Placental clearance averaged 0.62 and 0.77 mL/min for theophylline and antipyrine, respectively, and the clearance index of theophylline was 0.81 +/- 0.07. Although human and rabbit placentas are structurally dissimilar, the rabbit placenta perfused in situ appears to be a useful preparation for measuring the transfer processes and the related and governing factors, of different compounds. PMID- 1886415 TI - A new model of myocardial infarction in Yucatan minipigs. AB - Myocardial infarction studies in pigs have been complicated by the use of antiarrhythmic drugs or the high incidence of ventricular fibrillation. We report on a new model of experimental myocardial infarction in thiamylal-anesthetized Yucatan minipigs. These studies were performed in the absence of intravenous antiarrhythmic drugs. No animals required resuscitation during either surgery or reperfusion and only 19% were resuscitated during occlusion. Extensive systemic hemodynamic, regional contractility and coronary blood flow measurements were continuously obtained during left anterior descending coronary artery (LAD) occlusion (45 min) and reperfusion (240 min). Mean arterial blood pressure and left ventricular + dP/dt decreased during occlusion, and both declined further upon reperfusion. Persistent dysfunction (segmental shortening from 24.8 +/- 1.3 to 3.9 +/- 0.9% (p less than 0.001); pre-occlusion and 5 min post-occlusion, respectively) occurred immediately after occlusion in the myocardium perfused by the LAD, while late declines in segmental shortening (19.6 +/- 0.9 to 17.2 +/- 1.2%; pre-occlusion and 240 min post-reperfusion, respectively) were observed in myocardium perfused by the left circumflex coronary artery. While heart rate did not change during occlusion, tachycardia occurred at the onset of reperfusion. Although initial reactive hyperemia following reperfusion was manually inhibited, high LAD blood flow following reperfusion occurred early (0 to 60 min) but returned below pre-occlusion values late (180 to 240 min). The area at risk represented 23.1 +/- 0.9% (n = 34) of the left ventricle and 39.0 +/- 3.2% of this area was infarcted. Therefore, 9.2 +/- 0.9% of the left ventricle was infarcted. These data suggest that myocardical infarction in anesthetized minipigs can be achieved without the aid of intravenous antiarrhythmic drugs and reduced cardioversion. Therefore, this new model can be utilized in the evaluation of therapeutic compounds focused on altering the detrimental consequences of myocardical infarction. PMID- 1886416 TI - A methodological basis for improving the reliability of measurements of opiate abstinence responses in the guinea-pig ileum made dependent in vitro. AB - The purpose of this study was to find a neurogenic response of the isolated guinea-pig ileum that could serve as an internal standard to normalize abstinence responses, which are also neurogenic, during opiate dependence produced in vitro. The internal standard is required because of baseline variability in these responses of the ileum and a time-dependent decay in neuroeffector responsiveness with prolonged incubation. Systematic studies were made of the variability in the responses to neurogenic stimulation by 1) electrical field stimulation, 2) nicotinic stimulation, and 3) precipitation of opiate abstinence with opiate antagonists as well as studies of the time-dependent decay in responsiveness with prolonged incubation. The three neurogenic responses show covariation but the best correlation is found between the nicotinic and the abstinence responses. The nicotinic system presents a pharmacological sensitivity to specific acute opiate action and also shows an improving correlation with abstinence which develops with the progression of dependence. This correlation tends to a direct linear relation with a slope approaching 1.0. The nicotinic response of the ileum seems to be a valid internal control to normalize its abstinence responses after incubation with opiates for different intervals of time. PMID- 1886417 TI - A reliable technique for chronic carotid arterial catheterization in the rat. AB - A reliable and simple method for cannulating the carotid artery of rats is described. The rat was anesthetized with halothane. The right carotid artery located between the omohyoideus and sternohyoideus muscles was exposed through a 2-cm ventral neck incision. The catheter was made of Silastic tubing and a monofilament line, which served as an obturator and internal support. The line was then filled with a viscous mixture of heparin, polyvinylpyrrolidinone and normal saline to prevent the formation of blood clots. The catheter was advanced through the carotid artery towards the heart by a predetermined distance (15-20 mm) depending on the size of the rat. The catheter was well tolerated by the rats and the success rate was 95%. Its patency lasted for at least 7 days postsurgery without any special maintenance care. With the described method one would be able to perform repetitive blood sampling and arterial blood pressure measurements in unanesthetized and unrestrained rats for prolonged period after catheterization. PMID- 1886418 TI - Antibiotic interference with oral contraceptive steroid efficacy. PMID- 1886419 TI - Review of the incidence and clinical relevance of myeloid antigen-positive acute lymphoblastic leukemia. AB - An increasing number of papers document cases of acute leukemia in which individual blast cells co-express markers normally restricted to a single cell lineage. Numerous terms are used to refer to cases with unscheduled expression of lineage-foreign proteins; the best defined categories were hybrid acute leukemia and acute mixed-lineage leukemia. The incidence of phenotypically variant acute leukemia varies with the quality and quantity of parameters used and the stringency of the criteria employed for its definition. Considerable interest has focused on acute lymphoblastic leukemia (ALL) cells expressing one or several myeloid lineage-associated antigens (My+ ALL), CD13, CD14, CD15, CD33, and CDw65. Owing to legitimate and cryptic expression on lymphoid cells, CD11b and CD15 reagents may not be considered as specific indicators of myeloid differentiation. The reported incidence ranged from 5 to 46% in 14 studies on My+ ALL, totalling 3817 patients. Several detailed reports documented a higher incidence of My+ ALL in adults (realistically in the range 10-20%) than in children (5-10%) and in B lineage ALL as opposed to T-lineage ALL. My+ ALL cases are more likely to display unique cytogenetic [t(9;22), 11q23, 14q32] features than My-neg ALL. There appears to be no predominant expression of a single myeloid-associated antigen among those analyzed. As the morphological diagnosis of a leukemia subtype is often imprecise, some T-neg B-neg My+ ALL cases might actually contain FAB AML-M0 populations. While the expression of myeloid-associated antigens has no apparent prognostic significance in the majority of childhood ALL subtypes, in adults myeloid antigens seem to identify a high risk group of ALL patients with a poorer response to standard ALL therapy. PMID- 1886420 TI - Alpha interferon gene deletions in adults, children and infants with acute lymphoblastic leukemia. AB - DNA from 76 cases of acute lymphoblastic leukemia (ALL) was tested with a cDNA probe encoding the alpha 2B interferon (IFN) gene transcript. Deletions were found in three of ten pre-B, three of 21 T-cell, four of 22 common and one of 23 null ALL cases. Amongst those with null ALL were 20 infants, most with characteristic translocations, none of whom had deletion of alpha IFN genes. The results confirm that alpha IFN gene deletions may occur without visible abnormalities of chromosome 9p and show that they occur across a wide range of ALL phenotypes. The results suggest that alpha IFN gene deletions may be rare events in null ALL of infants but their incidence and cellular consequences remain unknown. PMID- 1886421 TI - Megakaryoblastic leukemia with an N-ras mutation and late acquisition of a Philadelphia chromosome. AB - A patient is described with de novo acute non-lymphocytic leukemia of megakaryoblastic lineage with tri-lineage myelodysplasia. This patient was studied cytogenetically and using molecular genetic techniques throughout her clinical course. She had an N-ras mutation at diagnosis which persisted despite a bone marrow transplant, and acquired a Philadelphia chromosome associated with a P190 BCR-ABL transcript at clinical relapse 3 months post-transplantation. PMID- 1886422 TI - Retinoic acid inhibits the expression of cytidine deaminase linked to the differentiation of the human leukemic cell line HL-60. AB - The activity of cytidine deaminase markedly increases during the differentiation of HL-60 cells induced by dimethylsulfoxide or 1,25-dihydroxy vitamin D3, but does not increase when the inducer is retinoic acid. Here it is demonstrated that retinoic acid inhibits the increase in cytidine deaminase activity elicited by the other two inducers. This inhibitory effect of retinoic acid (i) was not the result of a direct action on the enzymatic activity; (ii) was correlated with the differentiating effect of retinoic acid, as indicated by the similar time-course and dose-dependence of both effects, and by additional studies with various retinoids and with an HL-60 variant resistant to retinoic acid-induced differentiation; (iii) required the continued presence of the drug for more than 24 h, and could not be reversed after 48 h; (iv) was manifest, after a lag-time of 24 h, at whatever time retinoic acid was added during the 5 days of treatment of the cells with the differentiation inducers; and (v) was prevented by the addition of the protein synthesis inhibitor cycloheximide. These data indicate that retinoic acid negatively regulates the expression of cytidine deaminase in HL-60 cells, and suggest that this effect is mediated by a protein, the synthesis of which should be controlled by the nuclear receptor of retinoic acid. PMID- 1886423 TI - Short course high dose mitoxantrone with high dose cytarabine is effective therapy for adult lymphoblastic leukemia. AB - Mitoxantrone is effective in the treatment of acute myelogenous leukemia and, in combination with either vincristine-prednisone or cytarabine (HiDAc), it is also effective in acute lymphoblastic leukemia (ALL). As mitoxantrone exhibits a steep dose-response curve against ovarian cancer cells and acute myeloid leukemia cells in vitro, we evaluated the safety and efficacy of high dose mitoxantrone with HiDAc in the treatment of ALL. Patients received mitoxantrone 20-37.5 mg/m2 daily for 2 days or 1 dose of 40-80 mg/m2 and HiDAc 3 g/m2 over 3 h once daily for five doses. All eight of the patients with previously untreated disease and eight of ten patients with ALL in relapse achieved complete remission (CR). The untreated patients included two with Philadelphia positive ALL who also achieved CR (one after one course of mitoxantrone-HiDAc, and one after one course of mitoxantrone HiDAc followed by one additional dose of vincristine and daily prednisone). Seven of the eight previously untreated patients who achieved CR are still in remission. The one T-cell ALL has relapsed at 2 months after CR. The toxicity was acceptable. The regimen thus induces a remission rate equivalent to that of traditional vincristine-prednisone. The 'quality of remission' may be superior, and this therapy should be explored as a primary induction therapy in patients with ALL. PMID- 1886424 TI - Screening for expression of cytokines with hematopoietic growth factor activity by permanent human B-cell lines. AB - Using colony assays in semi-solid media, several investigators have shown that supernatants (SN) of normal and malignant human B-cells can stimulate the growth of granulocyte-macrophage (GM) progenitor cells. So far macrophage colony stimulating factor (M-CSF) and interleukin-6 (IL-6) have been identified as potential colony-stimulating activity (CSA) present in B-cell SN. However, other CSAs such as GM-CSF, G-CSF, IL-1-beta, IL-3, and IL-4 may also be candidates in this respect. Several human B-cell lines (CL) were screened for the expression of the respective genes at the mRNA and protein level. Constitutive production of GM CSF was detected in the lymphoblastoid CL Wi-L2-729-HF2 and in the Burkitt line Raji. The signal intensity of specific transcripts and the amount of protein being secreted increased upon exposure to the phorbol ester PMA. The hybridoma line HB-564 also expressed the GM-CSF gene, but required prior stimulation with PMA. 3H-thymidine incorporation of Raji and Wi-L2-729-HF2 cells was unchanged in the presence or absence of a specific neutralizing sheep anti-GM-CSF serum, suggesting that GM-CSF did not serve as an extracellular autocrine growth factor. The expression of the GM-CSF gene was independent of the proliferative state (log phase growth versus plateau phase growth) and of the presence of serum in cultures of the respective CL. The expression of G-CSF, IL-1-beta, IL-3, and IL-4 genes was not detectable in the CL at the mRNA level. PMID- 1886425 TI - Philadelphia chromosome positive precursor B-cell acute lymphoblastic leukemia with a translocation t(2;14)(p13;q32). AB - A female patient with precursor B-cell acute lymphoblastic leukemia (precursor B ALL) was analyzed cytogenetically. Karyotyping of the leukemic cells showed a Philadelphia chromosome (Ph1), and also showed a translocation between 2p13 and 14q32, which is thought to be specific for children with B-cell chronic lymphocytic leukemia. DNA analysis with both conventional and pulsed-field gel electrophoresis revealed the rearrangement of the c-abl gene, the BCR gene outside the 5.8 kb breakpoint cluster region (bcr or M-BCR), and the comigration of an abnormal Not I pHabl 5' and 3'-bcr fragment, indicating the presence of BCR/c-abl recombination. The JH gene was rearranged, but the JK gene showed a germline configuration, as with previously reported cases with a t(2;14). This case is the first report of a patient with Ph1-positive precursor B-ALL, in whom a specific translocation t(2;14)(p13;q32) is found simultaneously. PMID- 1886426 TI - Remission of juvenile chronic myeloid leukemia following graft failure of an unrelated marrow transplant and autologous recovery of marrow function promoted by GM-CSF and IL-3. AB - The unusual course of a boy with juvenile chronic myeloid leukaemia is presented. After bone marrow transplantation (BMT) from an unrelated donor followed by graft failure and subsequent stimulation by rhu GM-CFC and II-3, this patient experienced complete recovery of autologous haematopoiesis. At 17 months post-BMT the patient was off any therapy with completely normal blood counts and no signs of disease. PMID- 1886427 TI - Prognostic significance of BCR breakpoint location in M-bcr. PMID- 1886428 TI - "Persons of honour and reputation": the voluntary hospital in an age of corruption. PMID- 1886429 TI - An eighteenth-century medical hearing and the first observation of tropical phagedaena. PMID- 1886430 TI - Germ theories of disease and British veterinary medicine, 1860-1890. PMID- 1886431 TI - Powers of life and death: aspects of maternal welfare in England and Wales between the wars. PMID- 1886432 TI - The strange case of Field Marshall Sir John Dill. PMID- 1886433 TI - Comparison of expandable endotracheal stents in the treatment of surgically induced piglet tracheomalacia. AB - Present surgical alternatives for pediatric tracheobronchomalacia are limited and associated with many potentially undesirable complications. The feasibility of different intraluminal expandable endotracheal stents for the treatment of surgically induced tracheomalacia was analyzed in 27 piglets. A potentially fatal tracheomalacia was surgically created. Either a stainless steel "zig-zag" stent or a woven polymeric stent was then implanted. Tracheal patency, mucosal function, histopathologic respiratory tract changes, and effects of the stent on esophageal motility were evaluated over a 16-week period. Piglets with steel stents uniformly experienced intense inflammation leading to tracheal dysfunction and death. Piglets with polymeric stents experienced minimal respiratory symptoms. Expandable polymeric endotracheal stents alleviate surgically induced piglet tracheomalacia, were easy to insert, allowed for tracheal growth, and reduced the need for high-risk surgical procedures with prolonged ventilatory support. PMID- 1886434 TI - Use of intraoperative auditory brainstem responses to guide prosthesis positioning. PMID- 1886436 TI - Successful pediatric examinations using nasoendoscopy. PMID- 1886435 TI - Results of cochlear implant reinsertion. PMID- 1886437 TI - Clinical experience with the Lichtenberger endo-extralaryngeal needle carrier. PMID- 1886438 TI - Fabrication of a custom electrode endotracheal tube. PMID- 1886439 TI - cis-platinum ototoxicity in children. AB - Despite the recognized ototoxicity of cis-platinum, a clinical outline for the audiologic evaluation of patients receiving this drug has not been clearly defined. In a practical approach to this problem, the audiograms of 48 pediatric patients referred for monitoring during planned cis-platinum therapy were reviewed. Eleven patients tested with auditory brain-stem response (ABR) audiometry demonstrated several limitations of this modality. Fourteen children underwent initial ABR testing followed by at least two pure-tone audiograms. The remaining 23 patients had their hearing evaluated by pure-tone audiometry only. Various factors such as patient age, cis-platinum dosage, and cranial radiation exposure were analyzed for apparent effect. Younger patients tended to be more susceptible to audiologic changes with the administration of cis-platinum. The proportion of patients who demonstrated a hearing loss increased with successive dosing as did the severity of the hearing loss. Prior exposure to cranial radiation was strongly linked to the development of hearing loss following cis platinum therapy. Guidelines are presented regarding the use of clinical audiometry in the screening of these pediatric oncology patients. PMID- 1886440 TI - The treatment of small acoustic tumors: now or later? AB - Prior to the advent of microneurosurgery, the operative mortality for acoustic tumor removal was high and management often consisted of observation until sufficient symptoms warranted removal. The treatment of these tumors has evolved, and recent introduction of gadolinium-enhanced magnetic resonance imaging (MRI) allows the diagnosis of very small intracanalicular acoustic tumors before hearing has been significantly affected. For such tumors, some surgeons advocate the premicrosurgical philosophy of observation rather than removal. Our results of small acoustic tumor removal with attempt at hearing preservation were reviewed. From 1961 to June 1989, 39 acoustic tumors 0.5 cm or less were removed by the middle fossa approach. Measurable hearing was preserved in 67%, and facial function 1 year postoperatively was normal or nearly normal in 97%. There was no other permanent operative morbidity. Given our results, early surgical removal of small acoustic tumors is advocated. PMID- 1886441 TI - The intraoperative management of the thyroid gland during laryngectomy. AB - The standard of care of laryngeal cancer surgery is wide field excision of the larynx combined with ipsilateral thyroid lobectomy. A retrospective review of 247 laryngectomies performed between 1979 and 1989 was undertaken to determine specific intraoperative indications for thyroid gland removal. The incidence of thyroid disease in our patients with laryngeal cancer was compared to the normal population. Eight percent of thyroid specimens removed during laryngeal cancer surgery demonstrated invasion by squamous cell carcinoma. All patients having thyroid invasion had T3 or T4 laryngeal lesions that were stage IV at the time of surgery. All these lesions were found to have transglottic growth and laryngeal cartilage invasion by the pathologist. All of these patients also had abnormal thyroid glands intraoperatively and laryngeal cartilage destruction that was evident intraoperatively. Total thyroidectomy with bilateral paratracheal and pretracheal lymph node dissection is indicated when squamous cell carcinoma of the larynx involves the thyroid gland. Prophylactic ipsilateral thyroid lobectomy and isthmusectomy is warranted for large laryngeal cancers (T3, T4) that involve the anterior commissure, the subglottic area, or extend transglottically. Routine thyroid gland removal is not indicated for the majority of laryngeal cancers that do not meet the aforementioned criteria. Finally, abnormal thyroid histopathology was diagnosed in 37% of the surgical thyroid gland specimens removed during laryngectomy. PMID- 1886442 TI - Functional evaluation following microvascular oromandibular reconstruction of the oral cancer patient: a comparative study of reconstructed and nonreconstructed patients. AB - Over the past decade, the use of free flap transfers in head and neck surgery has led to remarkable advances in the reliability and the ultimate results of oromandibular reconstruction. Stable and retentive dental restorations have been achieved using enosseous implants placed directly into the vascularized bone flaps. However, the functional assessment of patients who underwent primary mandibular reconstruction with these techniques has not been previously reported. A group of 10 reconstructed and 10 nonreconstructed segmental hemimandibulectomy patients were compared using a battery of tests to assess their overall well being, cosmesis, deglutition, oral competence, speech, length of hospitalization, and dental rehabilitation. In addition, objective measures of the masticatory apparatus (interincisal opening, bite force, chewing performance, and chewing stroke) were used to compare these two groups as well as normal healthy subjects and edentulous patients restored with conventional and implant-borne dentures. The results show a clear advantage for the reconstructed patients in almost all categories. Persistent problems and future directions in oromandibular reconstruction are discussed. PMID- 1886443 TI - Computerized tomography and magnetic resonance imaging following cranial base surgery. AB - The computed tomography scans and magnetic resonance imaging films of 57 patients who underwent anterior or anterolateral cranial base surgery from January 1987 to August 1989 were retrospectively reviewed to ascertain the significance of early and late postoperative intracranial imaging changes. Extra-axial changes (air, blood, cerebrospinal fluid collection) were found in 96% of patients; axial changes (brain edema, contusion) were seen in 30% of patients in the first postoperative period (72 hours). Subsequently, extra-axial changes began to resolve but axial changes became more prevalent. After 6 months, only axial changes persisted (encephalomalacia). It was encouraging to find a low correlation of imaging abnormalities with clinically significant findings. PMID- 1886444 TI - Quantifying the spread of botulinum toxin through muscle fascia. AB - Botulinum toxin was recently approved for treating several head and neck dystonias. Paralysis of neighboring muscles is the major complication of its use. Spread of toxin from the injected muscle has been suggested as an etiology. This study examines how botulinum toxin crosses muscle fascia by a novel method of quantifying muscular paralysis. Botulinum toxin (0.2 to 10 U) was placed onto the fascia of rat tibialis anterior (TA) muscles (n = 6). Toxin was also placed on dose-matched muscles that had their fascia surgically removed (n = 6). Twenty four hours later, the nerve to the tibialis anterior was electrically stimulated to deplete the muscle fibers of glycogen. Toxin-paralyzed fibers retained their glycogen and appeared purple on periodic acid-Schiff (PAS) stain. Botulinum toxin easily passed through muscle fascia even at subclinical doses. The presence of fascia reduced the spread of botulinum toxin by 23%. These results suggest that spread of botulinum toxin can be prevented only by delivering small doses to the center of a target muscle. PMID- 1886445 TI - Otoacoustic emissions in normal and hearing-impaired children and normal adults. AB - Although distortion-product otoacoustic emissions (DPOEs) have been studied in adults recently, there is little information regarding them in young children. DPOEs and click-evoked otoacoustic emissions (CEOEs) were measured from a same group of normal and hearing-impaired children (age 4 through 10 years) and normal adults (age 22 through 29 years). Measurements of DPOEs in 13 children's ears with normal hearing showed higher levels of emissions in the 700- to 1400-Hz and 5.7-kHz regions relative to the data obtained in 10 normal adult ears. The 22 ears of children with sensorineural hearing loss demonstrated agreement between pure-tone audiograms and "DPOE audiograms." Measurements of CEOEs revealed that the average level of emission in 15 normal-hearing children's ears was slightly lower than that previously obtained in newborns, but slightly higher than that of adults. In children, the CEOE spectral components in the 4- to 6-kHz region were lower than in newborns, but higher than in adults. These results support the view that the DPOEs and CEOEs comprise a valuable tool in assessment of cochlear function in subjects of all ages. PMID- 1886446 TI - The natural history of epistaxis in hereditary hemorrhagic telangiectasia. AB - The purpose of this retrospective study is to document the natural history of epistaxis in patients with hereditary hemorrhagic telangiectasia. A telephone questionnaire was administered to 73 patients who had been previously screened for pulmonary arteriovenous malformations (PAVMs). The incidence of epistaxis in this population was 93%, with a mean onset age of epistaxis of 12 years, a mean frequency of bleeding of 18 episodes per month, and a mean duration of bleeding of 7.5 minutes. More than 90% of patients experienced the onset of epistaxis before the age of 21 and symptoms were progressive with age. There were no differences in the age of onset, frequency of epistaxis, or duration of epistaxis between patients with PAVMs versus those without PAVMs. Although the natural history of epistaxis does not predict the presence or absence of pulmonary arteriovenous malformations, epistaxis is an early marker of the disease, hereditary hemorrhagic telangiectasia, and might guide screening for pulmonary and cerebral arteriovenous malformations in children of affected parents. PMID- 1886447 TI - The oxygen and nitrous oxide indices of flammability of endotracheal tubes determined by laser ignition. AB - This study determines the flammability of polyvinylchloride (PVC), red rubber (RR), and silicone (Si) endotracheal tubes in oxygen- and nitrous-oxide-enriched atmospheres. Flammability is measured by using the oxygen and nitrous oxide indices of flammability with laser ignition. The laser-ignited oxygen (O2) index of flammability of the endotracheal tubes is: PVC, 0.25; RR, 0.19; Si, 0.20. The laser-ignited nitrous oxide (N2O) index of flammability of the endotracheal tubes is: PVC, 0.45; RR, 0.37; and Si, 0.41. These results are similar to the previously reported O2 and N2O indices of flammability with propane-torch ignition. This study validates the concept that the indices of flammability are useful measures of endotracheal tube flammability and are independent of the ignition source. PMID- 1886448 TI - cis-platinum ototoxicity in children. AB - Cis-platinum is an ototoxic antineoplastic drug. Evaluation of auditory thresholds in 33 children receiving cis-platinum shows that a threshold shift at 6 and 8 kHz is first measurable after a cumulative dose of 201 to 300 mg/m2. A 35 to 40-dB high-frequency threshold shift is evident after a cumulative cis platinum dose of 301 to 400 mg/m2. Increasing cumulative doses of cis-platinum are associated with a greater degree of hearing loss. Receiver-operator characteristic curves were used to find a criterion value that effectively identified threshold shifts that were due to cis-platinum ototoxicity. A 15-dB or greater shift in the 6- and 8-kHz threshold average identifies a high true positive (50%) and low false-positive (0%) rate of cis-platinum-induced hearing loss. Using this criterion, cis-platinum ototoxicity affected 77% of children who received cis-platinum (median cumulative dose 360 mg/m2). PMID- 1886449 TI - The embryonic development of the lateral nasal wall from 8 to 24 weeks. AB - This histological study of 20 fetal heads aged between 8 and 24 weeks of gestation demonstrates and describes the embryonic development of the lateral wall of the nose. The three turbinates (inferior, middle, and superior) arise as soft-tissue swellings (preturbinates) by 8 weeks' gestation. A cartilage capsule surrounds the nose at 8 weeks and by 9 weeks, medially directed flanges of cartilage have invaded all three preturbinates. The uncinate process arises from the medial surface of the lateral cartilaginous capsule and is first identifiable by 10 weeks. An "air space" progressively develops from 11 to 12 weeks lateral to the cartilaginous uncinate process and from this space, the embryonic channel to the maxillary sinus develops. The embryonic woven bone of the maxilla can be identified from 9 to 10 weeks and enlarges both absolutely and relatively to the nasal cavity, so that by 13 to 14 weeks, this expanding bone forms the lateral wall of the inferior meatus as the cartilaginous nasal capsule regresses. PMID- 1886450 TI - Origin of malignant centrofacial granulomas: surface markers and gene rearrangement of malignant cells. AB - Malignant centrofacial granuloma (MCFG) is a clinical entity characterized by a relentless ulceration of the upper airway involving the nose, palate, and face, without any demonstrable etiology. The origin of 11 cases were analyzed with the help of cell-surface immunostaining in all and with T-cell receptor gene (TCR) rearrangement in 3. The results show that most of the cases of MCFG are in fact T cell lymphomas with cell-surface antigens (CD2, CD7, CD3) consistent with either early or mature T lymphocytes. However, some cases exhibit B-lymphoid (CD19, CD20) or histiomonocytic (CD13, CD14) lineage-specific markers. In conclusion, despite its remarkable clinical unity, MCFG is a heterogeneous group of neoplastic diseases, most but not all of which may be classified as T-cell lymphoma. PMID- 1886451 TI - The use of an "internal standard" for control of the recovery in microdialysis. AB - Microdialysis of intravenously injected theophylline in blood and in lung tissue was performed in two rats during anaesthesia. The recovery (dialysate extraction fraction) in blood was greater than the recovery in lung tissue and there was a change in recovery with time both in blood and in lung. The concentrations of theophylline in the dialysates were corrected for the recovery using caffeine as an "internal standard" in the perfusate as well as tritiated water injected into the rats. There was excellent agreement between the two different methods. Furthermore, the corrected concentration of unbound theophylline in the blood was in accordance with the simultaneously measured total concentration of theophylline in plasma when binding to plasma proteins was taken into account. The conclusion is that an "internal standard" for correction of the recovery is a useful method to approach the true concentrations of compounds in the extracellular water. The "internal standard" must be as equal as possible to the substance of interest. PMID- 1886452 TI - Influence of diabetes on norepinephrine-induced inositol 1,4,5-trisphosphate levels in rat aorta. AB - The effects of norepinephrine on total tissue levels of inositol 1,4,5 trisphosphate were measured by protein binding assay in aortas from rats with chronic streptozotocin-induced diabetes and from age-matched control rats. In both control and diabetic aortas, norepinephrine induced a rapid, transient and concentration-dependent elevation of inositol 1,4,5-trisphosphate content during contraction. Maximum production of inositol 1,4,5-trisphosphate in response to norepinephrine was greater in diabetic than in control aortas. However, the sensitivities of control and diabetic aortas to norepinephrine for inositol 1,4,5 trisphosphate production were not significantly different. Enhanced norepinephrine-induced production of inositol 1,4,5-trisphosphate in diabetic aortas may contribute to the increased maximum contractile responsiveness of these arteries to the agonist. However, since enhanced contractile responses of diabetic aortas to norepinephrine were also detected at times when inositol 1,4,5 trisphosphate levels were not significantly increased, other factors also appear to be involved in mediating enhanced contractions of diabetic arteries to norepinephrine. PMID- 1886453 TI - Chronopharmacology of trichlormethiazide in rats; (II). Examination in aged rats. AB - We have previously demonstrated a time-dependent variability in the diuretic effects of trichlormethiazide, a thiazide diuretic agent, in young rats. The study suggested that the time-dependent variations in urinary trichlormethiazide and susceptibility of renal tissues to the agent might be involved in this phenomenon. The present study was undertaken to test a hypothesis that such a daily variation in the effects of trichlormethiazide is blunted by age. Trichlormethiazide (0.5 and 2.0 mg/kg) was given orally at 1200 hrs (day trial) or at 2400 hrs (night trial) in young (10-11 week old) and aged (23-24 month old) Wistar rats. Urine was collected for 8 hours after the agent and urinary excretions of sodium, chloride and trichlormethiazide were determined. Urine volume and urinary excretions of sodium, chloride and trichlormethiazide following the agent were significantly greater at 1200 hrs than at 2400 hrs in the young rats. However these administration time-dependent changes in the effects of trichlormethiazide and its urinary amount diminished in the aged rats. In the day and night trials, there were significant correlations between urinary trichlormethiazide and its effects (urine volume, urinary sodium and chloride) in both groups of rats. The regression lines in each parameter of two trials differed in the young, but not in the aged group of rats. These data indicate that the mode of the time-dependent changes in the effects of trichlormethiazide is altered in aged Wistar rats. Dampening of the time-dependent variations in urinary trichlormethiazide and susceptibility to the agent might be involved in these chronopharmacological alterations in aged rats. PMID- 1886454 TI - Angiotensin II mediates hyperadrenergic activity evoked by sodium restriction in essential hypertension. AB - We examined the possible involvement of angiotensin II in the modulation of circulating norepinephrine produced by acute sodium restriction in essential hypertensive patients (n = 18). Sodium restriction potentiated plasma level of norepinephrine in parallel with an increased plasma renin activity (r = 0.81, F = 31.2, p less than 0.05 given by the percent changes). An intravenous infusion of sarcosine-1, isoleucine-8 angiotensin II produced a significant fall in mean arterial pressure (-6 +/- 2 mmHg, p less than 0.05) in patients on sodium restriction but not before sodium restriction, while the infusion of the antagonist produced a greater decrease (p less than 0.05) in plasma norepinephrine with sodium restriction (-158 +/- 23 pg/ml, p less than 0.05) when compared to that obtained before sodium restriction (-91 +/- 11 pg/ml, p less than 0.05). A single oral administration of an angiotensin I converting enzyme inhibitor, captopril caused a greater fall (p less than 0.01) in mean arterial pressure after sodium restriction (-32 +/- 3 mmHg, p less than 0.05) compared to that given before (-21 +/- 3 mmHg, p less than 0.05). However, sodium restriction did not affect the magnitude of reflex increase in plasma norepinephrine to hypotension evoked by captopril (from +88 +/- 16 pg/ml to +87 +/- 17 pg/ml; p greater than 0.05). It can be interpreted that acute sodium depletion results in a substantial contribution of angiotensin II to the expression of hyperadrenergic activity. PMID- 1886455 TI - Influence of extract of Rosa rugosa roots on lipid levels in serum and liver of rats. AB - The effects of the methanol extract of Rosa rugosa roots on serum and liver lipids were studied in rats. The rats were fed the purified diets with or without the methanol extract at the 1% level for 4 weeks. The concentrations of serum and liver total cholesterol were not significantly affected by the feeding of extract. Feeding of the extract, on the other hand, reduced the liver triacylglycerol content without influencing the serum triacylglycerol level. The effects of the extract on lipids profiles were diminished markedly by dietary cholesterol. The results suggest an existence of component in the extract which may ameliorate the accumulation of triacylglycerol in rat liver. PMID- 1886456 TI - Clinical effects of methamphetamine vapor inhalation. AB - Despite the increasing popularity of crystalline methamphetamine ("ice") vapor inhalation, no investigations have reported drug plasma concentrations and effects. Under controlled laboratory conditions, six subjects were studied. Plasma concentrations of methamphetamine were determined, and subjective and cardiovascular effects were measured. Methamphetamine appeared in plasma rapidly, increased slowly over the next four hours and then progressively declined. The dose of methamphetamine administered produced modest ratings of subjective drug effects, and moderate changes in cardiovascular parameters. Both subjective and cardiovascular effects rapidly decreased despite the presence of sustained concentrations of methamphetamine in plasma. PMID- 1886457 TI - Stress-induced hypertension: effects of adrenalectomy and corticosterone replacement. AB - The effect of adrenalectomy on the hypotensive response induced by social deprivation was studied in a line of Wistar-derived rats. Prior removal of the adrenal gland by surgery was found to prevent the elevation in systolic or diastolic blood pressure observed in sham-operated isolated rats. The social deprivation-induced hypertensive response ran parallel with an increase in the levels of plasma corticosterone. Supplementation therapy with this glucocorticoid in previously adrenalectomized animals restored the levels of plasma corticosterone to normal and made the rats able to respond to social deprivation with an elevation in arterial pressure. Thus, corticosterone plays a "permissive" role in the elevation of blood pressure due to isolation. Apparently, this effect is dependent upon genetic, maturational and environmental factors since it is only evident in some lines of Wistar rats. PMID- 1886458 TI - Acute encephalopathy with hepatic steatosis induced by pantothenic acid antagonist, calcium hopantenate, in dogs. AB - In Japan, acute encephalopathy with hepatic steatosis resembling Reye's syndrome has been reported to occur after treatment with the pantothenic acid antagonist, calcium hopantenate. We studied the causal relationship and the pathogenesis in dogs. The agent was administered to seven dogs at increasing doses over a period of 8 weeks. Anorexia, vomiting, and diarrhea were common clinical findings. In four dogs, coma suddenly developed after the appearance of gastrointestinal signs. Three animals died during periods when they were not under direct observation. The effects of the agent appear to be related to dose. Laboratory findings representing significant changes at the time of coma included hypoglycemia, leukocytosis, hyperammonemia, hyperlactatemia, and elevated levels of serum transaminases. Microvesicular hepatic steatosis and mitochondrial abnormalities were consistent pathological findings. The hepatic mitochondria were enlarged and characterized by an increased number of cristae and the presence of crystalloid inclusions. In a second group of four dogs, pantothenic acid was given in addition to and in the same amount as calcium hopantenate at increasing doses over a period of 8 weeks. All four dogs survived the 8 weeks and only one developed mild anorexia. No significant biochemical changes were found and neither hepatic steatosis nor mitochondrial abnormalities were observed. The addition of pantothenic acid prevented the development of the disorder in the four animals. These results show that calcium hopantenate produces acute encephalopathy with hepatic steatosis in dogs, by inducing a deficiency of pantothenic acid. The hepatic mitochondrial changes of this reaction differ from those of Reye's syndrome. PMID- 1886459 TI - Histological changes of the liver in experimental graft-versus-host disease across minor histocompatibility barriers. V. A light and electron microscopic study of the intralobular changes. AB - Intralobular changes of the liver in experimental graft-versus-host disease (GVHD) across minor histocompatibility barriers were investigated for up to 14 months after bone marrow transplantation. Sinusoidal lymphocyte infiltration, and necrosis and degeneration of hepatocytes were evident by day 4 and reached a maximum level at 2 weeks after transplantation, then gradually decreased, but they persisted during the entire period of observation, indicating that more or less hepatocyte injury may persist continuously in hepatic GVHD. Piecemeal necrosis was transiently observed around 2 weeks after transplantation, in parallel with the peak of lymphocyte infiltration into the portal area. Similarly, central vein endothelialitis (attachment of lymphocytes to endothelial cells) was transiently observed with a peak activity at 2 weeks after transplantation. Mild centrilobular and portal fibroplasia were evident by 2 weeks after transplantation, but they hardly progressed and no cases developed liver cirrhosis. Frequently lymphocytes were found located beneath endothelial cells and attached to hepatocytes. Ultrastructural observation revealed that sinusoidal lymphocytes were occasionally in contact with endothelial cells by means of cytoplasmic pseudopods. Also lymphocytes were frequently in close contact with hepatocyte plasma membranes over short distances. Lymphocytes occasionally accompanied other inflammatory cells, such as eosinophilic leukocytes and mononuclear phagocytic cells. Hepatocytes in close contact with lymphocyte and other inflammatory cells showed a varying degree of degenerative changes, including condensation of cytoplasm and nucleus with irregular nuclear contours, dilatation of endoplasmic reticulum and mitochondria, formation of cytoplasmic vacuoles, and loss of microvilli.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1886460 TI - Angiomyolipoma of the liver: immunohistochemical study of a case. AB - Angiomyolipoma, a not uncommon tumor of the kidney, is rarely encountered in the liver. We report a case of angiomyolipoma of the liver in a 68-year-old woman, in which immunohistochemical study was performed. PMID- 1886461 TI - The effect of taurine on the cholestatic potential of sulfated lithocholate and its conjugates. AB - The present study was aimed at determining whether the protection by taurine of lithocholate-sulfate-induced cholestasis is mediated by conjugation or by direct effect of the amino acid on bile formation. Injection of free and conjugated (glycine and taurine) sulfated lithocholate in guinea pigs significantly reduced the secretion rate of non-sulfated bile acids in bile. There was no decrease in bile flow after the injection of taurine-conjugated sulfated lithocholate, which was completely recovered in bile within 60 min. In contrast, injection of sulfated lithocholate and its glycine conjugate led to a marked decrease in bile flow, and neither one was significantly recovered in bile. In addition, both caused morphological changes in the liver, characterized by the accumulation of cytoplasmic vacuoles with lamellated myelin figures characteristic of phospholipidosis. Pretreatment with taurine (0.5% in drinking water for 3 days) prevented both the drop in bile flow and the histological changes in the liver, suggesting that conjugation with taurine removed the cholestatic potential of sulfated lithocholate. However, since taurine was effective not only in preventing cholestasis induced by the free form of sulfated lithocholate but also against its glycine conjugate, these results suggest that other mechanisms in addition to conjugate must be involved. PMID- 1886462 TI - Psychiatric expert testimony: are the criticisms justified? (Part 2). PMID- 1886463 TI - Psychiatric malpractice: recent clinical loss experience in the United States. AB - This article presents a survey of recent trends in psychiatric malpractice litigation and its consequences in the United States. More particularly, it investigates the factors that trigger such litigation, the nature of the complaints and claims, the characteristics of patient and psychiatrist and the cost it involves for the parties concerned. PMID- 1886464 TI - AIDS: some medico-legal aspects. AB - The increase in HIV infection in South Africa poses serious problems not only to medical services in this country, but also to its legal system. Some of the more immediate medico-legal problems surrounding AIDS are discussed: Informed consent to the testing for HIV antibodies, the maintenance of confidentiality and the question of whether health care workers may refuse to treat AIDS patients. PMID- 1886465 TI - Abortion: in search of a constitutional doctrine (Part 1). AB - This article addresses the highly controversial topic of abortion from a constitutional angle. It discusses and analyses the landmark United States decision of Roe v Wade, the fundamental arguments of pro-choice and pro-life supporters, the difficulties inherent in the pro-choice and pro-life options and the abortion situation in South Africa, and concludes with proposals for a future Bill of Rights. PMID- 1886466 TI - The rights of children in law. PMID- 1886467 TI - The handling of prisoners in the Bophuthatswana Prisons Service in general and medical care in particular. PMID- 1886468 TI - Drug abuse--user accountability: is it a victimless crime? AB - This article examines the principles of drug-user accountability. It examines the broader concepts of accountability in terms of individual responsibility (including criminal responsibility), the actions and the consequences of such actions, in terms of the self and others. Recent and prevailing governmental and public opinions are evaluated and appropriate sanctions are examined. Medico legal aspects and dilemmas affecting the issues of the pathology of drug addiction and the nature and degree of impairment of responsibility as part of the addictive process, are analysed. A combined approach blending effective treatment, appropriate legal sanctions and community sanctions as an ultimate process to achieve demand and supply reduction universally, is proposed. PMID- 1886469 TI - The social impact of drug abuse on community life. AB - Drug abuse is often accompanied by a devastating social impact upon community life. The present article focuses on the adverse effect of drug abuse on industry, education and training and the family, as well as on its contribution to violence, crime, financial problems, housing problems, homelessness and vagrancy. PMID- 1886470 TI - Drug abuse: consequences in terms of family pathology and disintegration. AB - This article examines some of the consequences of drug addiction in terms of family pathology and family disintegration. It briefly elucidates the role of the family in developing and maintaining drug addiction in family members. The concept of 'secondary' sufferers of the illness of drug addiction is examined. An actual case history will be presented in order to facilitate analysis of some of the forms of pathology and disintegration so often seen in the family of the drug addict. Within the family context, the question of who, if anyone, is the victim of drug addiction, is raised. PMID- 1886471 TI - Introduction: physiologic adaptations to exercise training in cardiac patients: contemporary issues and concerns. AB - This symposium dealt with contemporary issues and concerns in cardiac rehabilitation. Selected topics included: the potential of exercise training to enhance coronary collateral circulation; safety and efficacy of high intensity training; influence of beta-blocking agents on exercise prescription and trainability; value of physical conditioning in patients with left ventricular dysfunction or cardiac transplantation; and the effect of exercise on serum lipids and lipoproteins. Each article attempted to assimilate the physiologically germane literature in an area and provide the reader with associated clinical and practical implications. PMID- 1886472 TI - Exercise training and coronary collateral circulation. AB - This review examines the potential for an exercise-induced increase in coronary collateral circulation, with specific reference to the role and functional significance of collateral vessels, highlighting animal and human studies in particular, and their inherent methodological limitations. Exercise training may enhance myocardial oxygen supply by promoting transient periods of myocardial ischemia, a potent trigger of collateral growth. Some human studies have shown that moderate-to-high intensity training can result in a higher double product at the onset of angina and/or ischemic ST-segment depression, suggesting that myocardial oxygen supply has increased. Attempts to use thallium-201 exercise scintigraphy to assess myocardial perfusion before and after a physical training program have produced conflicting data, whereas angiographic studies in group trials have, without exception, yielded disappointing results. Thus, direct evidence that exercise stimulates collateralization in humans is lacking. PMID- 1886473 TI - Exercise training in patients with impaired left ventricular function. AB - Advances in the understanding of the pathophysiology of congestive heart failure have guided efforts in formulating effective treatment strategies. The epidemiology, etiology, and medical management of congestive failure are reviewed. The changing approaches to exercise and exercise training in patients with heart failure are discussed. Recent studies of the impact of exercise training in this important patient group are presented. PMID- 1886474 TI - Physiologic adaptations to prolonged high-intensity exercise training in patients with coronary artery disease. AB - Exercise training elicits numerous beneficial adaptations in patients with coronary artery disease (CAD), but until 10 yr ago these adaptations were generally believed to be peripheral adaptations rather than improvements in myocardial blood supply. However, animal models of CAD have been shown to elicit improvements in myocardial blood flow and left ventricular performance with prolonged, intense exercise training. More recently we have provided electrocardiographic, echocardiographic hemodynamic, and radionuclide evidence of central cardiovascular adaptations in patients with CAD after a year-long program of 1 h of exercise at 70-90% of VO2max 5 d.wk(-1). These training-induced adaptations are consistent with an improvement in myocardial oxygenation and concomitantly an enhanced left ventricular function in these patients. This program also resulted in improvements in glucose tolerance, insulin sensitivity, and plasma lipoprotein-lipid profile. We have also shown that these beneficial cardiovascular and metabolic adaptations are maintained during six additional years of training in patients with CAD. These results do not imply that all patients with CAD should initiate such an intense training program, but rather that, in selected patients undergoing a training stimulus well in excess of that conventionally prescribed for coronary patients, the training-induced adaptations may be substantially greater than previously believed. PMID- 1886475 TI - Exercise training, serum lipids, and lipoprotein particles: is there a change threshold? AB - The role of lipoprotein manipulation in the treatment of atherosclerosis is well established. Improvement in lipoprotein cholesterol concentrations and subclass distribution through exercise training is often advised prior to pharmacologic intervention. As with other therapeutic interventions, dose must be stipulated to the patient. The dose of exercise training required to induce beneficial lipoprotein changes is unclear. This issue is further complicated by the potential effect of exercise training on lipoprotein subclass distribution (LDL I, LDL II, LDL III, LDL IV, HDL2a, HDL2b, HDL3a, HDL3b, HDL3c), enzymes, apoproteins, and transfer proteins and by the changes in diet and body composition that often accompany exercise training. These changes may be responsible for all or part of the lipoprotein change attributed to exercise. From available data, it appears that a threshold of approximately 15 miles.wk(-1) of jogging may be required to induce beneficial change. PMID- 1886476 TI - Exercise training after cardiac transplantation. AB - During the last decade, cardiac transplantation has become the accepted form of treatment for selected patients with end-stage heart disease, which usually results from dilated cardiomyopathy or coronary artery disease. Although 5-yr survival is currently 85%, patients have complicated courses after surgery, with an ever present risk of infection and graft rejection. Because of physical inactivity and severe limitation of cardiac output preoperatively, these deconditioned patients are excellent candidates for medically supervised rehabilitative exercise training programs. Denervation of the myocardium, which occurs with cardiac transplantation, results in a loss of autonomic nervous system modulation of cardiac output, with reliance on circulating catecholamines and with a delayed heart rate and cardiac output response to the onset of exercise. Oxygen uptake kinetics are prolonged, and maximal oxygen uptake is reduced. Additional abnormalities in cardiac and pulmonary artery pressures and in ventilation during exercise have been described. The literature contains seven studies concerning the effects of exercise training in cardiac transplant recipients. Benefits resulting from training include increases in maximal oxygen uptake, peak exercise power output, anaerobic threshold, and lean body mass, reduced perceived exertion, heart rate, and blood pressure during submaximal exercise, and a lowered resting heart rate and blood pressure. There are no data to suggest that exercise training alters the incidence of infection or rejection or improves longevity or return to pre-illness lifestyle. PMID- 1886477 TI - Influence of lifetime cross-country skiing on plasma lipids and lipoproteins. AB - Low concentrations of total and LDL cholesterol are associated with minimal risk of atherosclerosis. Aerobic exercise has been similarly associated with a low risk of heart disease. The literature is inconclusive as to whether there is an association between total and LDL cholesterol and exercise. Further, previous work has, almost exclusively, examined male runners. Therefore, we examined 176 male and female cross-country skiers, participating in the National Master's Championships, for body composition, dietary habits, exercise habits, and serum lipid levels. Our results show markedly low concentrations of serum LDL cholesterol and total cholesterol, as well as the expected high concentrations of HDL cholesterol and low concentrations of triglycerides, in these lean skiers. Their diets contained 30% fat, and they exercised 9 h weekly. Although it is difficult to separate the effects of diet, leanness, and exercise on the lipid profile, it is apparent that the lifestyle led by these people is associated with a lipid profile that confers an extremely low risk of atherosclerotic disease. PMID- 1886478 TI - Effects of exercise training on glucose control, lipid metabolism, and insulin sensitivity in hypertriglyceridemia and non-insulin dependent diabetes mellitus. AB - Exercise training has potential benefits for patients with hyperlipidemia and/or non-insulin dependent diabetes mellitus. In nondiabetic, nonobese subjects with hypertriglyceridemia, exercise training alone increased insulin sensitivity, improved glucose tolerance, and lowered serum triglyceride and cholesterol levels. These improvements did not occur when exercise training alone was given to similar patients with impaired glucose tolerance. In severely obese (X = 125 kg) subjects without diabetes melitus, a 600 calorie diet alone decreased glucose and insulin concentrations and improved glucose tolerance but did not increase insulin sensitivity. The addition of exercise training improved insulin sensitivity. Obese, non-insulin dependent diabetes mellitus subjects on sulfonylurea therapy alone increased insulin levels but failed to improve insulin sensitivity or glucose levels. In contrast, the addition of exercise training to this medication resulted in improved insulin sensitivity and lowered glucose levels. We conclude that exercise training has major effects on lowering triglyceride levels in hyperlipidemic subjects and can potentiate the effect of diet or drug therapy on glucose metabolism in patients with non-insulin dependent diabetes mellitus. PMID- 1886479 TI - Responses to varying rates of carbohydrate ingestion during exercise. AB - The purpose of this study was to determine how the ingestion of carbohydrate at varying rates influences physiological, sensory, and performance responses to prolonged exercise at 65-75% VO2max. Ten subjects ingested either a water placebo (WP) or carbohydrate solutions formulated to provide glucose at the rates of 26, 52, and 78 g, h-1 during 2 h of cycling exercise in a cool (10 degrees C) environment. Beverages were administered in a double-blind, counterbalanced design. A 4.8 km performance test followed each 2 h session. The average time required to complete the performance test was less with the carbohydrate feedings than with WP: mean (+/- SE) for WP = 505.0 +/- 18.7 s. 26 g.h(-1) = 476.0* +/- 8.8 s. 52 g.h(-1) = 483.8 +/- 12.7 s. 78 g.h(-1) = 474.3* +/- 19.1 s; *P less than 0.05 vs WP. Carbohydrate feeding resulted in higher plasma glucose and insulin, and lower free fatty acid concentrations than did WP. Changes in plasma osmolality, plasma volume, rectal temperature, lactate, heart rate, respiratory exchange ratio, ratings of perceived exertion, and sensory responses were similar among beverage treatments. Compared with WP, ingestion of the glucose beverages minimized changes in plasma ACTH and cortisol. In summary, carbohydrate feeding at the rates of 26 and 78 g.h(-1) was associated with improved exercise performance. The data further indicate that a dose-response relationship does not exist between the amount of carbohydrate consumed during exercise and exercise performance. PMID- 1886480 TI - Ventilatory response to sustained hypoxia during exercise. AB - The ventilatory stimulating effects of hypoxia occurring at carotid bodies are potentiated by exercise. However, hypoxia also has central ventilatory depressive effects; the potential interactions between this hypoxic depression and exercise have not been studied. We examined the ventilatory response to a 20 min period of isocapnic hypoxia (end-tidal O2, PETO2, of 50 mm Hg), preceded and followed by a 5 min period of isocapnic hyperoxia in seven normal adult males at rest and during moderate exercise (45-75 W). When hypoxia was introduced at rest (PETO2 = 42 mmHg), ventilation initially increased from 13.73 +/- 3.04 (mean +/- SD) to 23.69 +/- 5.48 1.min-1 and then slowly declined to 19.01 +/- 4.68 1 min-1. The increase was caused by increases in tidal volume and respiratory frequency, but the decline was solely in tidal volume. During a background of moderate exercise (PETCO2 = 46 mmHg), introduction of hypoxia caused ventilation to increase from 30.84 +/- 6.31 to 56.44 +/- 10.58 1.min-1. Ventilation subsequently did not decline; at the end of the hypoxic period, ventilation was 57.06 +/- 12.59 1.min 1. The increase was also associated with an increase in tidal volume and respiratory frequency, as seen as rest, but with much larger magnitudes. Despite the absence of ventilatory decline, there was still a decline in tidal volume, but it was compensated by an increase in respiratory frequency. We conclude that exercise potentiated the acute ventilatory response to hypoxia by modifying both tidal volume and respiratory frequency but that exercise abolished or greatly reduced hypoxic decline by increasing respiratory rate. PMID- 1886481 TI - Mood state and running economy in moderately trained male runners. AB - The purpose of this study was to determine the relationship between psychological states as measured by the Profile of Mood States (POMS) inventory and within subject variation in running economy (RE) in moderately trained male runners (N = 10). Subjects (ages 20-34 yr) were monitored during treadmill running, five times a week (Monday through Friday) for 4 wk, at 2.68, 3.13, and 3.58 m, s-1. Tension, depression, anger, vigor, fatigue, confusion, and a total mood disturbance (TMD) score were assessed every Friday prior to the treadmill running sessions. Oxygen consumption (VO2) was determined via the open-circuit method during each of the three running paces. VO2 values were averaged over 5 d and three speeds for each week (RE) and were correlated with the weekly TMD scores, resulting in a nonsignificant group correlation of r = -0.28. The within-subject group correlation between TMD scores and RE was r = 0.88. This positive correlation indicates that, when the focus of attention was on within-subject variation, weeks featuring more economical values were associated with more positive mental health profiles. Correlations between average VO2 and the six POMS subscales were tension. r = 0.81; depression, r = 0.73; anger, r = 0.58; vigor, r = -0.60: fatigue, r = 0.18; and confusion, r = 0.60. All correlation coefficients except for fatigue were significantly (P less than 0.01) related to average VO2. In conclusion, it appears that short-term fluctuations in RE of moderately trained male runners are closely tied to their mood state. PMID- 1886482 TI - Self-monitored exercise at three different RPE intensities in treadmill vs field running. AB - The aims of the present study were a) to compare the outcome of running exercise performed on a treadmill (laboratory) and an outdoor track (field) using an RPE production protocol and b) to study this kind of protocol used over time (3-5 wk). A group of 11 healthy male subjects participated, with ages varying from 33 to 65 yr (mean = 42.9 +/- 11.0 yr). Two test sessions consisting of both treadmill and track exercise were performed in a rotated order to control for sequential effects. All subjects exercised according to an identical protocol: two successive trials (3 min each) at RPE 11 (light exertion), followed by a RPE 13 (somewhat hard) trial (11 min) and, finally, a RPE 15 (hard) trial (5 min). Results show significantly different levels of heart rate (HR), blood lactate, and velocity at the three RPE levels. Large differences were also observed in all measured variables between field and laboratory. These differences were consistent over time. A high internal consistency, measured by test-retest reliability (alpha greater than 0.9), was obtained for both velocity and HR between the first two trials at RPE 11. In conclusion, the RPE method functioned well as a means of monitoring and regulating exercise intensity. PMID- 1886483 TI - Effects of strength training on lactate threshold and endurance performance. AB - To determine the effects of 12 wk of strength training on lactate threshold (LT) and endurance performance, 18 healthy untrained males between 25 and 34 yr of age were randomly assigned to either strength training (N = 10) or control (N = 8) groups. Despite no changes in treadmill VO2max or cycle peak VO2, a 33 +/- 5% increase (P less than 0.001) in cycling time to exhaustion at 75% of peak VO2 was observed following training. No significant changes in cycling time were observed in the control group. There were significant reductions in plasma lactate concentration at all relative exercise intensities ranging between 55 and 75% of peak VO2 training. The improved endurance performance was associated with a 12% increase in LT (r = 0.78, P less than 0.001). The strength training program resulted in significant improvements (P less than 0.001) of 31 +/- 5% and 35 +/- 7% in isokinetic peak torque values for leg extension and flexion, respectively, at a velocity of 30 degrees.s-1. There were also significant increases in 1-RM values of 30 +/- 4% (P less than 0.001) for leg extension, 52 +/- 6% (P less than 0.001) for leg flexion, and 20 +/- 4% (P less than 0.001) for the bench press. These findings indicate that strength training improves cycle endurance performance independently of changes in VO2max. This improved performance appears to be related to increases in LT and leg strength. PMID- 1886484 TI - Metabolic responses to drafting during front crawl swimming. AB - We examined the metabolic responses to front crawl swimming when following directly behind (drafting) another swimmer. Seven trained male swimmers participated as subjects. VO2max (l.min-1) was measured during a progressive tethered swim test and was also estimated from a 20 s sample of expired air collected immediately after an all-out, 549 m (600 yard) swim. On different days, each subject performed two 549 m trials at 95% of his maximal swim velocity, one with drafting and one without drafting, using a counter-balanced design. Underwater pace lights were used to establish the predetermined swim velocity. Drafting significantly reduced post-exercise VO2 (2.85 +/- 0.63 vs 3.12 +/- 0.66 l.min-1), blood lactate (3.4 +/- 0.6 vs 5.0 +/- 0.5 mM), and rating of perceived exertion (11.7 +/- 0.4 vs 14.9 +/- 0.5) (P less than 0.05). A repeated measures ANOVA (condition X distance) also revealed significant reductions in HR during the 549 m swim (137.7 vs 146.8 beats.min-1) (P less than 0.05). The results indicate that drafting results in a decrease in energy expenditure for the range of speeds examined. PMID- 1886485 TI - Physiological responses to wrist weights during endurance cycling in normal subjects. AB - Cardiopulmonary and metabolic responses were studied in 12 healthy males aged 45 +/- 7 yr (mean +/- SD) during 25 min of cycling exercise with (WW) and without (NW) arm swing with wrist weights at 60% and 75% of their maximal heart rate reserve (MHRR). Cycling leg work was adjusted in order to produce a constant 60% and 75% of MHRR during WW and NW sessions. The results revealed that during both exercises the cardiopulmonary and hemodynamic responses were similar. However, during the NW sessions lactic acid (LA) levels were significantly (P less than 0.01) higher than those observed during WW sessions (3.2 +/- 0.9 and 5.4 +/- 1.5 mm.l-1, vs 2.9 +/- 0.9 and 3.8 +/- 1.3 mm.-1), as were ratings of perceived exertion (RPE) (13.2 +/- 1 and 14.4 +/- 0.6, vs 12.2 +/- 1 and 13.4 +/- 1.5). These data indicated a similar pattern of hemodynamic and respiratory responses to NW and WW cycling exercises, while LA and RPE were lower in WW cycling. It is therefore suggested that arm swing with wrist weights may be a beneficial mode of exercise, distributing the workload on a larger muscle mass while maintaining the target heart rate. Thus, it enables a lower reliance on anaerobic metabolism and a lower perceived exertion. PMID- 1886486 TI - Effect of training on VO2max, thigh strength, and muscle morphology in septuagenarian women. AB - The purpose of this study was to determine the effects of a long-term (50 wk) combined aerobic-resistance training program on maximal oxygen consumption (VO2max, thigh strength, and vastus lateralis fiber morphology in healthy septuagenarian women (mean age = 72 +/- 6 yr). Subjects volunteered to be in either an exercise (Ex; N = 17) or control (Con; N = 10) group. Con subjects were 34% less active in winter than in summer, Ex subjects maintained their summer activity level on exercise days in winter. Initial, intermediate (20 wk), and final (50 wk) measurements were made for isokinetic knee extension/flexion strength; VO2max and morphological measurements from a muscle biopsy were made at the initial and final times only. Both groups gained in leg strength (Ex = +6.5%; Con = +7.8%; P less than or equal to 0.05) during the summer; in the winter the Ex group maintained leg strength and the Con group declined 12.2% (P less than or equal to 0.05). The fast-twitch muscle fiber area (Type IIb) increased 29% (P less than or equal to 0.001) in the Ex group and declined 26% (P = 0.014) in the Con group. VO2max increased only in the Ex group (16%; P less than 0.001). We conclude that healthy septuagenarian women can increase aerobic capacity, leg strength, and Type IIb muscle fiber area with a long-duration, combined aerobic resistance exercise program. PMID- 1886487 TI - Physical activity, body composition, and blood pressure: a multimethod approach. AB - The purpose of the current investigation was to evaluate, using multiple measures of physical activity, the relationships among physical activity, body composition, resting heart rate, and blood pressure in an adult population. Subjects were 221 male (135 normal weight, 86 overweight) and 221 female (156 normal weight, 65 overweight) subjects participating in a longitudinal study of cardiovascular risk factors in families. All subjects were administered three physical activity questionnaires. Principal components analyses were conducted to reduce measures into empirically derived subscales; this analysis revealed five stable factors in men and four in women. Results indicated that aerobic/leisure time significantly correlated to body composition and resting heart rate in both men and women. Additionally, aerobic/leisure time activity was related to blood pressure in women, and moderate activity was related positively to blood pressure in men. No other form of activity (e.g., light activity, anaerobic activity) was related to either adiposity or blood pressure. The implications of these results are discussed, and future research directions are highlighted. PMID- 1886488 TI - Validation of the 12-min swim as a field test of peak aerobic power in young men. AB - The purposes of this study were to validate the 12-min swim as a field test of VO2max and to compare its validity with that of the 12-min run. Thirty-six young men completed 12-min swim, 12-min run, tethered swimming (TS) VO2peak, and treadmill running (TR) VO2peak tests within 3 wk. Mean (+/- SD) 12-min swim and run distances were 581 +/- 88 and 2797 +/- 290 m, and mean TS and TR VO2peak values were 50.3 +/- 6.2 and 57.2 +/- 5.5 ml.kg BW-1.min-1, respectively. Correlation coefficients and standard errors of estimate for predictions of TS VO2peak from the 12-min swim (0.40 and 5.7 ml.kg BW-1.min-1) and run (0.74 and 4.2 ml.kg BW-1.min-1) and for predictions of TR VO2peak from the 12-min swim (0.38 and 5.1 ml.kg BW-1.min-1) and run (0.88 and 2.6 ml.kg BW-1.min-1) indicated that the 12-min run was a more accurate predictor of TS or TR VO2peak than the 12 min swim. We conclude that the 12-min swim has relatively low validity as a field test of peak aerobic power and that it should not be considered an equally valid alternative to the 12-min run in young male recreational swimmers. However, the accuracy of predicting VO2peak from the 12-min swim is as good as some other commonly used methods, and, therefore, it may be adequate for fitness classification in situations in which a high level of accuracy is not needed. PMID- 1886489 TI - Trend analysis for repeated measures designs. PMID- 1886490 TI - Comparison of serological and chemical characteristics of capsular polysaccharides of Cryptococcus neoformans var. neoformans serotype A and Cryptococcus albidus var. albidus. AB - The antigenic formula and chemical structure of capsular polysaccharide (CPS) of Cryptococcus albidus var. albidus (C. albidus) were studied in relation to those of C. neoformans var. neoformans serotype A (C. neoformans A). The results of slide agglutination tests with factor sera and reciprocal adsorption experiments showed that antigenic formula of C. albidus was the same as that of C. neoformans A. The soluble CPSs from the two species were obtained from culture supernatants by precipitation with ethanol followed by purification by chromatography on DEAE cellulose column. The structural analyses of such CPSs from the two species showed that the antigenic CPS fractions consisted of a backbone of alpha(1-3) linked D-mannopyranosyl residues with a single branch of beta(1-2)-xylose or glucuronic acid, and mostly with O-acetyl groups, in which side chains and O acetyl groups were responsible for antigenic specificity. It was found that there was a minor difference between the CPS of C. neoformans A and that of C. albidus; in the former, unsubstituted mannose residues existed in a low frequency, but in the latter none. Moreover, the 1H-nuclear magnetic resonance spectra of partially hydrolyzed acidic fragments of the two CPSs indicated that two xylose side chains were present between glucuronic acid side chains. Taken together, it was suggested that these two species of C. neoformans A and C. albidus are closely related to each other in their CPSs. PMID- 1886491 TI - Production of H2O2 by alveolar macrophages in experimental allergic alveolitis. AB - Experimental extrinsic allergic alveolitis (EAA) was induced in guinea pigs with Saccharopolyspora rectivirgula. Bronchoalveolar lavages were performed before inducing EAA (day 1, BAL 1), on day 23 (BAL 2), and on day 48 (BAL 3). The number of cells/ml in lavage fluid was increased at BAL 2 (4.79 x 10(6) and BAL 3 (4.29 x 10(6)) compared with BAL 1 (0.56 x 10(6)). The number of major cell types increased simultaneously, neutrophil becoming the predominant cell type over alveolar macrophages (AM). The production of H2O2 by AM was measured at the different phases of EAA. Adherent AM were either non-stimulated or triggered with phorbol myristate acetate (PMA), zymosan. S. rectivirgula opsonized with normal guinea pig serum (SRNS), or S. rectivirgula opsonized with guinea pig anti-S, rectivirgula serum (SRAS). Stimulated AM produced larger quantities of H2O2 than unstimulated cells, PMA being the most potent stimulus. At day 1, AM stimulated with S. rectivirgula and zymosan produced similar quantities of H2O2. After the induction of the disease, AM stimulated with S. rectivirgula produced larger quantities of H2O2 than with zymosan. Production of H2O2 by AM stimulated with S. rectivirgula or PMA, respectively, stayed the same at day 1 and 23, but increased sharply for both stimuli at day 48. There was no difference between H2O2 production by AM triggered with SRNS or with SRAS.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1886492 TI - Plasmid incidence rate and conjugative chloramphenicol and tetracycline resistance plasmids in Malaysian isolates of Salmonella typhi. AB - Seven (6.1%) of 115 strains of Salmonella typhi isolated from Malaysian patients harbored a single large plasmid of 71 to 166 mD. Two of the seven plasmid-bearing strains were resistant to chloramphenicol (Cm) and tetracycline (Tc) and they transferred Cm and Tc resistance traits to Escherichia coli K12 at frequencies from 1.6 x 10(-7) to 1.9 x 10(-6). Agarose gel electrophoresis provided evidence that the resistance traits were cotransferred on a conjugative plasmid. The significance and importance of these results are discussed. PMID- 1886493 TI - In vitro and in vivo transferrable beta-lactam resistance due to a new plasmid mediated oxyiminocephalosporinase from a clinical isolate of Proteus mirabilis. AB - A new plasmid-mediated beta-lactamase (FPM-1) with an isoelectric point of 7.2 and a molecular weight of 26,000 was found in a cefuroxime-resistant clinical isolate of Proteus mirabilis strain 6003. FPM-1 can be classified as a type I oxyimino-cephalosporinase on the basis of its substrate specificity and inhibition pattern by clavulanic acid etc., and its conferred resistance on both the strain and transconjugants against most oxyme-type cephalosporins as well as the older ones but not against cefamycins and a few exceptional oxyme-type cephalosporins such as ceftizoxime, ceftazidime and cefixime. In a murine systemic infection model, only these FPM-1-stable drugs exhibited protective activity against the FPM-1-producing P. mirabilis 6003 similar to that against a nonproducing derivative strain. The FPM-1-mediated cefuroxime resistance in P. mirabilis 6003 was transferred to co-infected Escherichia coli 7004 at frequencies between 3.8 x 10(-3) and 4.0 x 10(-2) in a murine ascending urinary tract infection model. In the same infection model due to the FPM-1-producing E. coli transconjugant, FPM-1-stable cefixime was significantly more effective than FPM-1-labile cefteram pivoxil, although both drugs had similar therapeutic effect against its FPM-1-nonproducing counterpart strain. PMID- 1886494 TI - Study tour USA. PMID- 1886495 TI - Impressions of American midwifery. PMID- 1886496 TI - When the stork doesn't call. PMID- 1886497 TI - Scotland's first water baby. PMID- 1886498 TI - Objectives and targets for the maternity services. PMID- 1886499 TI - [Antimycotic agents. Progress in treatment of mycoses]. PMID- 1886500 TI - [Ciguatera: an undesirable vacation souvenir]. PMID- 1886501 TI - Live donation of human body parts: a case for negotiability? PMID- 1886503 TI - Expert evidence. PMID- 1886502 TI - Alcohol and violence. PMID- 1886504 TI - Rumpole among the doctors. PMID- 1886505 TI - Politics and practice in the supply of water. PMID- 1886506 TI - Fludarabine. PMID- 1886507 TI - [The effect of oral N-acetylcysteine on glutathione concentration in bronchoalveolar lavage of patients with fibrosing lung diseases]. AB - Glutathione (GSH) is an important constituent in protecting the cellular elements within the lower respiratory tract against oxydants. We measured GSH in bronchoalveolar lavage fluid (BAL) in twelve patients with lung fibrosis and compared the data to eight healthy controls. GSH in BAL was 0.71 +/- 0.34 mumol/l in patients with lung fibrosis and 0.88 +/- 0.35 mumol/l in the controls (p greater than 0.05). After relating GSH on the volume of the epithelial lining fluid (ELF), determined by the urea method, GSH/ELF was 93 +/- 71 mumol/l in lung fibrosis and significantly different (p less than 0.005) from 387 +/- 240 mumol/l in the controls. In seven patients (four lung fibrosis, one desquamative pneumonitis, two asbestosis) GSH in BAL was determined before and after seven days of medication with 1800 mg N-acetylcysteine/day. We observed a significant increase of GSH in BAL from 0.93 +/- 0.46 to 1.56 +/- 0.92 mumol/l. Our observations confirm that in patients with lung fibrosis the protective ability against oxydants is diminished and that one parameter of the antioxydative capacity (GSH) can be increased in BAL by oral administration of N acetylcysteine. Further studies are necessary to investigate the clinical and therapeutic implications of our findings. PMID- 1886508 TI - [Course and diagnosis of pulmonary Kaposi sarcoma in patients with AIDS]. AB - Diagnosis of pulmonary Kaposi's sarcoma can be difficult. Clinical findings and chest X-rays are non-specific and endobronchial diagnostic in about 50% of cases. Additional concomitant infectious complications are frequent. Symptomatic pulmonary Kaposi's sarcoma most oftenly is progressive and has a poor prognosis. Preliminary data suggest effective palliation with radio- and chemotherapy and an improved survival time in selected cases. We present six cases of proven pulmonary Kaposi's sarcoma and discuss clinical course and diagnostic difficulties. Based on this view we propose a diagnostic approach to warrant therapeutic success. PMID- 1886509 TI - [Esophageal motility disorders with thoracic pain of unknown origin]. AB - 35 patients with angina-like chest pain underwent esophageal manometry after a coronary artery disease had been ruled out by angiography. Furthermore, patients after gastric or esophageal surgery, with pathologic upper gastrointestinal endoscopy or with pathologic gastroesophageal reflux as seen on 24-hour-pH-metry were excluded from this study. 29 out of 35 patients (83%) had a normal manometric study, six patients (17%) had a motility disorder; five of these showed an unspecific dismotility pattern and were asymptomatic while the study was done; only one patient presented with esophageal spasm. Since only this latter patient was symptomatic while the study was done, a correlation between symptoms and this motility disorder seems likely. --If pathologic gastroesophageal reflux has been ruled out, esophageal manometry can establish a diagnosis in only 3% of patients with angina-like chest pain without esophageal symptoms (dysphagia, odynophagia, heartburn or regurgitation). We conclude that this complicated examination should not be done in these patients. PMID- 1886510 TI - [Ferritin in acute leukemia. Serum ferritin concentration as a nonspecific tumor marker for M1 and M2 myeloid leukemia]. AB - Serum ferritin concentration was studied in 136 patients with different types of acute leukemia. Pretreatment serum ferritin concentrations in the immature myeloblastic leukemia (M1 and M2 of the FAB-classification of acute leukemias) was found to be highly increased compared to the more mature types of acute myeloblastic leukemias (M3 to M5) and the acute lymphoblastic leukemias (L1 to L3). Investigation of the intracellular ferritin concentration showed, that the serum ferritin levels paralleled the intracellular ferritin concentration within the leukemic blasts. Within the immature myeloic blasts (M1) the intracellular ferritin concentration was 14-fold increased compared to normal granulocytes. This correlated with the 17-fold increased serum ferritin levels in these patients. Intracellular ferritin concentrations within the leukemic blasts of more mature types of acute leukemia (M3 to M5) were found to be only slightly increased. These data support the concept, that an increased synthesis and release of ferritin by the leukemic blasts is responsible for the increased serum ferritin concentration. This concept is also supported by the observation, that a further increase of serum ferritin concentration was seen during a cytotoxic chemotherapy. It is noteworthy, that this increase was more pronounced in the immature leukemias obviously caused by a loss of intracellular ferritin from the damaged leukemic blasts. The serum ferritin levels followed closely the activity of the disease. Increased pretreatment serum ferritin concentrations normalized completely when patients achieved complete remission. In contrast, in patients with tumor relapse or tumor progression serum ferritin concentrations increased again. These data suggest that the serum ferritin in immature myeloblastic leukemia has the characteristics of a tumor associated marker.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1886511 TI - [Metolazone in the treatment of advanced therapy-resistant dilated cardiomyopathy]. AB - Ten patients (eight male/two female) with advanced dilated cardiomyopathy (NYHA III/IV) and a mean fractional shortening in two-dimensional echocardiogram of 20% (9 to 30%) and a mean sodium excretion of 21 mmol (8 to 40 mmol) per day, pretreated with digoxin, captopril and a mean frusemide-dose of 147 mg (80 to 500 mg) without an effective diuresis, were additional treated with 2.5 to 5 mg oral metolazone daily. All patients had a brisk diuresis within 24 hours and a mean weight loss of 8.9 kg (3 to 20 kg) until discharge. All patients improved considerably by additional metolazone-therapy. Seven patients developed a mild hyponatraemia (122 to 132 mmol/l), seven showed mild (greater than or equal to 3.2 mmol/l) and one had a serious hypokalaemia (2.8 mmol/l); spironolactone pretreated patients developed no hypokalaemia. Notably none of the patients had serious blood pressure fluctuation or a deterioration of renal function. To avoid severe electrolyte-disturbances, additional metolazone-therapy should be practised in hospital, preferring low-dose metolazone and reducing frusemide-dose under careful biochemical monitoring after diuresis is started. PMID- 1886512 TI - [Nuclear medicine diagnosis in bronchial cancer]. PMID- 1886513 TI - [From mucolytic agent to free radical capture: N-acetylcysteine]. PMID- 1886514 TI - [Peak performance medicine: beneficial for the patient--damaging for personnel. Approaches to understanding and prevention of burnout in the helping occupations, especially in intensive care]. PMID- 1886515 TI - [Liver cirrhosis and alpha 1-antitrypsin deficiency]. PMID- 1886516 TI - [Official position of the German Diabetes Society. Use of instruments for blood glucose self monitoring]. PMID- 1886519 TI - Microbiological degradation of pesticides in yard waste composting. AB - Changes in public opinion and legislation have led to the general recognition that solid waste treatment practices must be changed. Solid-waste disposal by landfill is becoming increasingly expensive and regulated and no longer represents a long-term option in view of limited land space and environmental problems. Yard waste, a significant component of municipal solid waste, has previously not been separated from the municipal solid-waste stream. The treatment of municipal solid waste including yard waste must urgently be addressed because disposal via landfill will be prohibited by legislation. Separation of yard waste from municipal solid waste will be mandated in many localities, thus stressing the importance of scrutinizing current composting practices in treating grass clippings, leaves, and other yard residues. Yard waste poses a potential environmental health problem as a result of the widespread use of pesticides in lawn and tree care and the persistence of the residues of these chemicals in plant tissue. Yard waste containing pesticides may present a problem due to the recalcitrant and toxic nature of the pesticide molecules. Current composting processes are based on various modifications of either window systems or in-vessel systems. Both types of processes are ultimately dependent on microbial bioconversions of organic material to innocuous end products. The critical stage of the composting process is the thermophilic phase. The fate and mechanism of removal of pesticides in composting processes is largely unknown and in need of comprehensive analysis. PMID- 1886517 TI - Genetic regulation of human immunodeficiency virus. AB - Human immunodeficiency virus (HIV) has a complex life cycle in which both cellular and virus-encoded factors participate to determine the level of virus production. Two of the viral genes, tat and rev, are essential for virus replication and encode novel trans-activators that interact specifically with their cognate RNA target elements. Elucidation of their mechanisms of action is likely to expand our knowledge of gene regulation at transcriptional and posttranscriptional levels in the eukaryotic cell. Several viral genes (vif, vpu, and vpr) facilitate virus infection and/or release and may play a role in target cell tropism and infection in vivo. The functions of yet other viral genes (nef, vpt) remain unclear. Recent data also suggest that the tat gene product may have a role in HIV pathogenesis that goes beyond trans-activating virus expression. It can potentially impact on uninfected cells as a diffusible molecule and alter the growth of different cell types. PMID- 1886518 TI - Genetic basis of virulence in Shigella species. AB - Shigella species and enteroinvasive strains of Escherichia coli cause disease by invasion of the colonic epithelium, and this invasive phenotype is mediated by genes carried on 180- to 240-kb plasmids. In addition, at least eight loci on the Shigella chromosome are necessary for full expression of virulence. The products of these genes can be classified as (i) virulence determinants that directly affect the ability of shigellae to survive in the intestinal tissues, e.g., the aerobactin siderophore (iucABCD and iutA), superoxide dismutase (sodB), and somatic antigen expression (rfa and rfb); (ii) cytotoxins that contribute to the severity of disease, e.g., the Shiga toxin (stx) and a putative analog of this toxin (flu); and (iii) regulatory loci that affect the expression of plasmid genes, e.g., ompR-envZ, which mediates response to changes in osmolarity, virR (osmZ), which mediates response to changes in temperature, and kcpA, which affects the translation of the plasmid virG (icsA) gene which is associated with intracellular bacterial mobility and intracellular bacterial spread. A single plasmid regulatory gene (virF) controls a virulence-associated plasmid regulon including virG (icsA) and two invasion-related loci, i.e., (i) ipaABCD, encoding invasion plasmid antigens that may be structural components of the Shigella invasion determinant; and (ii) invAKJH (mxi), which is necessary for insertion of invasion plasmid antigens into the outer membrane. PMID- 1886521 TI - Dissimilatory Fe(III) and Mn(IV) reduction. AB - The oxidation of organic matter coupled to the reduction of Fe(III) or Mn(IV) is one of the most important biogeochemical reactions in aquatic sediments, soils, and groundwater. This process, which may have been the first globally significant mechanism for the oxidation of organic matter to carbon dioxide, plays an important role in the oxidation of natural and contaminant organic compounds in a variety of environments and contributes to other phenomena of widespread significance such as the release of metals and nutrients into water supplies, the magnetization of sediments, and the corrosion of metal. Until recently, much of the Fe(III) and Mn(IV) reduction in sedimentary environments was considered to be the result of nonenzymatic processes. However, microorganisms which can effectively couple the oxidation of organic compounds to the reduction of Fe(III) or Mn(IV) have recently been discovered. With Fe(III) or Mn(IV) as the sole electron acceptor, these organisms can completely oxidize fatty acids, hydrogen, or a variety of monoaromatic compounds. This metabolism provides energy to support growth. Sugars and amino acids can be completely oxidized by the cooperative activity of fermentative microorganisms and hydrogen- and fatty-acid oxidizing Fe(III) and Mn(IV) reducers. This provides a microbial mechanism for the oxidation of the complex assemblage of sedimentary organic matter in Fe(III)- or Mn(IV)-reducing environments. The available evidence indicates that this enzymatic reduction of Fe(III) or Mn(IV) accounts for most of the oxidation of organic matter coupled to reduction of Fe(III) and Mn(IV) in sedimentary environments. Little is known about the diversity and ecology of the microorganisms responsible for Fe(III) and Mn(IV) reduction, and only preliminary studies have been conducted on the physiology and biochemistry of this process. PMID- 1886520 TI - Mucor dimorphism. AB - Mucor dimorphism has interested microbiologists since the time of Pasteur. When deprived of oxygen, these fungi grow as spherical, multipolar budding yeasts. In the presence of oxygen, they propagate as branching coenocytic hyphae. The ease with which these morphologies can be manipulated in the laboratory, the diverse array of morphopoietic agents available, and the alternative developmental fates that can be elicited from a single cell type (the sporangiospore) make Mucor spp. a highly propitious system in which to study eukaryotic cellular morphogenesis. The composition and organization of the cell wall differ greatly in Mucor yeasts and hyphae. The deposition of new wall polymers is isodiametric in yeasts and apically polarized in hyphae. Current research has focused on the identity and control of enzymes participating in wall synthesis. An understanding of how the chitosome interacts with appropriate effectors, specific enzymes, and the plasma membrane to assemble chitin-chitosan microfibrils and to deposit them at the proper sites on the cell exterior will be critical to elucidating dimorphism. Several biochemical and physiological parameters have been reported to fluctuate in a manner that correlates with Mucor morphogenesis. The literature describing these has been reviewed critically with the intent of distinguishing between causal and casual connections. The advancement of molecular genetics has afforded powerful new tools that researchers have begun to exploit in the study of Mucor dimorphism. Several genes, some encoding products known to correlate with development in Mucor spp. or other fungi, have been cloned, sequenced, and examined for transcriptional activity during morphogenesis. Most have appeared in multiple copies displaying independent transcriptional control. Selective translation of stored mRNA molecules occurs during sporangiospore germination. Many other correlates of Mucor morphogenesis, presently described but not yet explained, should prove amenable to analysis by the emerging molecular technology. PMID- 1886522 TI - Iso- and anteiso-fatty acids in bacteria: biosynthesis, function, and taxonomic significance. AB - Branched-chain fatty acids of the iso and anteiso series occur in many bacteria as the major acyl constituents of membrane lipids. In addition, omega-cyclohexyl and omega-cycloheptyl fatty acids are present in several bacterial species. These two types of fatty acids are synthesized by the repeated condensation of malonyl coenzyme A with one of the branched-chain and cyclic primers by the same enzyme system. The pathway of de novo branched-chain fatty acid synthesis differs only in initial steps of synthesis from that of the common straight-chain fatty acid (palmitic acid) present in most organisms. The cell membranes composed largely of iso-, anteiso-, and omega-alicyclic acids support growth of bacteria, which inhabit normal as well as extreme environments. The occurrence of these types of fatty acids as major cellular fatty acids is an important criterion used to aid identification and classification of bacteria. PMID- 1886525 TI - [Current findings on cystic fibrosis]. PMID- 1886524 TI - Growth rate of Escherichia coli. AB - It should be possible to predict the rate of growth of Escherichia coli of a given genotype in a specified environment. The idea that the rate of synthesis of ATP determines the rate of growth and that the yield of ATP determines the yield of growth is entrenched in bacterial physiology, yet this idea is inconsistent with experimental results. In minimal media the growth rate and yield vary with the carbon source in a manner independent of the rate of formation and yield of ATP. With acetate as the carbon source, anapleurotic reactions, not ATP synthesis, limit the growth rate. For acetate and other gluconeogenic substrates the limiting step appears to be the formation of triose phosphate. I conclude that the rate of growth is controlled by the rate of formation of a precursor metabolite and, thus, of monomers such as amino acids derived from it. The protein-synthesizing system is regulated according to demand for protein synthesis. I examine the conjecture that the signal for this regulation is the ratio of uncharged tRNA to aminoacyl-tRNA, that this signal controls the concentration of guanosine tetraphosphate, and that the concentration of guanosine tetraphosphate controls transcription of rrn genes. Differential equations describing this system were solved numerically for steady states of growth; the computed values of ribosomes and guanosine tetraphosphate and the maximal growth rate agree with experimental values obtained from the literature of the past 35 years. These equations were also solved for dynamical states corresponding to nutritional shifts up and down. PMID- 1886523 TI - Domains in microbial beta-1, 4-glycanases: sequence conservation, function, and enzyme families. AB - Several types of domain occur in beta-1, 4-glycanases. The best characterized of these are the catalytic domains and the cellulose-binding domains. The domains may be joined by linker sequences rich in proline or hydroxyamino acids or both. Some of the enzymes contain repeated sequences up to 150 amino acids in length. The enzymes can be grouped into families on the basis of sequence similarities between the catalytic domains. There are sequence similarities between the cellulose-binding domains, of which two types have been identified, and also between some domains of unknown function. The beta-1, 4-glycanases appear to have arisen by the shuffling of a relatively small number of progenitor sequences. PMID- 1886526 TI - [The life style and physical activity of the child operated on for congenital cardiopathy]. AB - The parents of 151 children operated on for congenital heart disease have answered some questions about the scholastic, extrascholastic and physical activity of their children. Approximately 94% of the children are at the correct school level for their age. Extrascholastic activities of the city children is the same as children living in the country. During their free time 22% of the child population engages in physical activity, whereas 78% of the child population engages in physical activity at school. Among the parents, 61% think the activity of their children is normal, and 27% think it is too active. Our results demonstrate that the children operated on for congenital heart disease have a normal life during scholastic and free time, whereas, the introduction of these children to sport activities is anomalous and insufficient. PMID- 1886527 TI - [Growth in stature in infantile-juvenile obesity]. AB - The study aimed to assess the effect of juvenile simple adiposity on growth. The height (measured using a Hapenden stadiometer) of 1443 subjects (799 boys and 644 girls) aged from 6 to 16 was measured. The Quetelet index (QI) of adiposity was used; all subjects examined exceeded the 95th centile of the standard Cronk and Roche scale. Heights are expressed as standard deviation scores (SDS) and are compared to the British Standard. Adipose boys are taller than British boys up to the age of 12, then the difference lessens and the average heights of 15-year-old adipose boys are below the 50th centile of British growth charts. Female subjects showed a higher SDS from 6 to 8 years, after which the difference lessens gradually, and after 13 years the average height is below the 50th centile of British standards. Adipose boys are taller than normal boys during childhood; in prepuberty and puberty this difference lessens and during puberty they are shorter than British boys. This growth model is probably due to advanced skeletal maturity in adipose subjects with the result that at puberty growth lessens because it is exhausted. The wide epidemiological cross-sectional study confirms that growth is favourable in juvenile adiposity but does not alter adult height. PMID- 1886529 TI - [The Guillain-Barre syndrome. The clinico-electrophysiological correlations]. AB - The authors refer about clinico-electrophysiological correlations in children with Guillain-Barre syndrome (GBS). The dates confirm the diagnostic and prognostic value of electrodiagnostic studies in GBS, so that the authors suggest an electrodiagnostic protocol. According to the authors, independently of the extent of electrophysiological abnormalities, young age has a favourable influence on the restoration of conduction abnormalities and on the evolution of damage to peripheral neurones. PMID- 1886528 TI - [The GHRH test in Turner's syndrome]. AB - GHRH test was performed in 11 girls suffering from Turner's syndrome ranging in age from 5.6-13.5 years. GH peak resulted lower than 10 ng/ml in three subjects, who had also shown reduced GH values after two conventional pharmacological stimuli (L-dopa- and insulin-induced hypoglycemia) and a value of mean GH concentration over 24 hours lower than 3 ng/ml. Both GH peak and area under the curve were not correlated with height, height velocity, bone age/chronological age ratio, GH peak after conventional pharmacological stimuli and mean GH value of spontaneous secretion. The comparison with the results of GHRH test in other kinds of short stature evidenced in girls with Turner's syndrome the presence of GH values (peak and area under the curve) higher than those in subjects with "classical" GH deficiency, lower than those in "short normal stature" and similar to those in subjects with "non classical" GH deficiency. In conclusion, our data suggest, even if within a certain variability of the responses, a possible involvement of GH deficiency to the pathogenesis of short stature in Turner's syndrome, suggesting the existence of a prevalent hypothalamic nature of GH deficiency. PMID- 1886530 TI - [Achalasic megaesophagus with onset in the 1st year of life. A case report]. AB - We report a case of esophageal achalasia in a nine months old baby. Recurrent cough and cyanosis were the most important clinical findings. Esophagomyotomy remarkably improved the clinical symptoms. Disorders of esophageal motility may be an important cause of respiratory emergencies in the first year of life. PMID- 1886531 TI - [Pseudotumor cerebri due to the cessation of corticosteroids. A case report]. AB - Cerebral pseudotumour is an endocranial hypertensive syndrome marked by the absence of focal neurological signs, the integrity of neuroradiological tests and an increased liquor pressure with normal composition of the liquor itself. It is normally self-limiting but if endocranial hypertension persists it may severely affect sight. It may be idiopathic or secondary to a number of conditions. The authors report a case of cerebral pseudotumour following the suspension of corticosteroid treatment. The pathology resolved rapidly following lumbar puncture. The paper focuses on the pathogenetic mechanisms and the still undefined therapeutic possibilities. PMID- 1886532 TI - [Persistent bradycardia and apnea due to hypothyroidism in a very low-weight newborn infant]. AB - Alterations in thyroid function are quite heterogeneous in VLBW preterm neonates. The case of a 1160-g newborn is reported, affected by severe RDS and persistent bradycardia during the first week of life, who later developed symptoms and signs of low-output cardiac failure. ECG showed low QRS. Echocardiography revealed small pericardial effusion. Therapy with L-thyroxine led to rapid improvement of clinical conditions and to normalization of ECG and echocardiographic pattern. Levels of thyroid hormones should be monitored in VLBW infants, since their deficiency may play a role in compromised clinical conditions. PMID- 1886533 TI - [The effects of treatment with growth hormone alone or in combination with oxandrolone in a group of Turner's syndrome children. A preliminary study]. AB - The authors analyzed the clinical and psychological effects of GH (group 1) and GH plus oxandrolone (group 2) in a group of 11 Turner girls aged 6.3-14 years. The results showed a significant improvement of posttreatment height velocity vs pretreatment height velocity for both study groups. No significant differences were found between the two groups. A girl of group 2 manifested a defect of sexual identification. PMID- 1886534 TI - Effects of chronic carbon disulfide inhalation on sensory and motor function in the rat. AB - Chronic carbon disulfide (CS2) exposure produces debilitating motor, sensory and neuropsychiatric consequences in humans. Sensory, especially auditory, tests have been considered for indexing early intoxication. This study examines effects of chronic CS2 exposure in rat upon auditory and neuromuscular function using reflex modulation audiometry to test the feasibility of using pure tone detection thresholds as such an index. This method is sensitive to the differential effects of toxicants upon acoustic and neuromuscular functioning. Rats were tested before, during and after five or 12 weeks of 500 ppm CS2 inhalation, six h/day, five days/week. Neuromuscular integrity, reflected by baseline startle amplitude, decreased 50% after five weeks and 67% following 12 weeks of CS2 exposure; recovery to 70% of preexposure values occurred on the fourth postexposure week. Twelve weeks of CS2 inhalation had no significant effect upon acoustic thresholds. Pure tone detection thresholds, therefore, do not appear adequate to index early CS2 exposure levels in the rat, as severe neuromuscular compromise occurred at a time when acoustic thresholds remained stable. PMID- 1886535 TI - Sexual orientation in male rats prenatally exposed to ethanol. AB - Previous studies have shown that prenatal ethanol exposure causes feminization of the male offspring, as evidenced by display of female sexual response (lordosis), when mounted by a stud male. In the present study we examined whether or not the feminization induced by prenatal ethanol exposure also affected a different aspect of sexually motivated behavior, namely, the approach towards a receptive female normally displayed by male rats. The testing apparatus consisted of an open-field arena with two small boxes in which were placed the stimulus animals, in one box a male rat, in the other a receptive female. The partition between the stimulus and the experimental animals consisted of a metal net allowing both animals to see and smell each other without actual physical contact. The tendency to approach the receptive female or the male was assessed by the proportion of the observation period the experimental male spent near the receptive female or the male rat, respectively. The experiment was performed on the adult male offspring of mothers consuming a liquid diet containing 5% ethanol, giving rise to a daily ethanol intake of about 14 g/kg. One group of control mothers was given a liquid diet without alcohol but isocaloric with the alcohol-containing diet. Another control group had free access to water and lab chow. The results showed that male offspring of both control groups devoted 29% of the observation period near the receptive female as compared to 13% near the male. The ethanol exposed males on the other hand devoted as much time, 20%, to the male as to the receptive female.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1886536 TI - Prenatal nicotine exposure increased susceptibility to electroconvulsive shock (ECS) in adult rats. AB - Female rats were treated during pregnancy (days 1-20) with nicotine (1 mg/kg SC, b.i.d.). When some aspects of maternal behavior and developmental parameters were recorded in mothers and pups, respectively, no changes were detected in the experimental group as compared with controls. However, adult offspring of nicotine-treated rats showed an increased susceptibility to ECS. These results demonstrate long-lasting deleterious effects induced by nicotine exposure during fetal life. PMID- 1886537 TI - Quantification of glial fibrillary acidic protein: comparison of slot immunobinding assays with a novel sandwich ELISA. AB - Detailed protocols are presented for assaying glial fibrillary acidic protein (GFAP), an astrocyte localized protein which serves as a quantitative marker of toxicant-induced injury to the central nervous system. Two different solid-phase assay procedures are described: 1) a nitrocellulose based slot-immunobinding assay and 2) a novel microtiter plate based sandwich ELISA. The performance of both assays was assessed by measuring the content of GFAP in homogenates of specific regions of the rat brain and in homogenates of brain regions damaged by the prototype neurotoxicants, trimethyltin (TMT) and 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP). Both procedures gave similar results that were consistent with previously published observations. By comparing the simplicity, cost effectiveness, safety and speed of the two methods, it appears likely that the sandwich ELISA has several advantages over slot-immunobinding assays. PMID- 1886539 TI - Developmental toxicity of the dopamine agonist pergolide mesylate in CD-1 mice. II: Perinatal and postnatal exposure. AB - Pergolide mesylate is a dopamine agonist and, therefore, reduces prolactin secretion. In Experiment I, pregnant mice were given oral doses of 0, 0.1, 0.3, 1.0 or 3.0 mg/kg/day pergolide on GD 15 through PD 10 or 20 to identify a tolerated dose which would not markedly reduce offspring survival during late gestational and lactational exposure. Offspring survival was not affected at any dose, but dose-related decreases in progeny body weights occurred at weaning. On PD 10, suckling-induced increases in maternal serum prolactin concentrations did not occur in dams treated with 3.0 mg/kg/day. In Experiment II, pregnant mice were given oral doses of 0, 0.002, 0.1 or 3.0 mg/kg/day pergolide on GD 15 through PD 20. Dams were allowed to deliver and maintain their offspring throughout a 21-day lactation period. Growth and behavioral performance of one F1 male and one F1 female per litter were monitored, followed by a reproduction trial and terminal organ weight measurements. There were no treatment-related effects on maternal body weights, food consumption, or terminal organ weights and pathology. Three dams showed overt signs of mammary inflammation and lactational insufficiency and mean progeny survival was decreased slightly in the 3.0 mg/kg/day group. There were no adverse effects on growth, development or reproductive performance in the F1 treatment-derived generation. Neonatal negative geotaxis, 1-h activity levels at 30 and 60 days of age, auditory startle habituation at 55 days of age, and two-way active avoidance performance at 65 days of age were not affected significantly by treatment. Thus doses of pergolide that did not inhibit lactation completely in the F0 dams were found to have no enduring effects on offspring development. PMID- 1886538 TI - Developmental toxicity of the dopamine agonist pergolide mesylate in CD-1 mice. I: Gestational exposure. AB - Pergolide was given by oral gavage to mated CD-1 female mice at doses of 0, 1, 20, or 60 mg/kg/day on gestation days (GD) 6-15. Animals assigned to the teratology segment were killed on GD 18 for evaluation of maternal organ weights, and fetal viability, weights and morphology. Animals assigned to the postnatal segment were allowed to deliver and physical development and behavioral performance of the progeny were monitored until weaning. Maternal organ weights were collected at termination after weaning. One F1 offspring per sex per litter was maintained for postweaning physical, behavioral and reproductive assessments and for terminal examinations and organ weight evaluations. No adverse effects of pergolide treatment were found in the 1 mg/kg/day group. Dose-related hyperactivity, chewing and squinting that were consistent with dopaminergic stimulation occurred following dosing in the 20 and 60 mg/kg/day groups; F0 body weights and food consumption were reduced during the initial phase of treatment in the 60 mg/kg/day group. Gravid uterine weights and fetal weights were decreased in the 60 mg/kg/day group of the teratology segment, but there was no indication of teratogenicity in any group. Mammary inflammation, attributed to increased progeny suckling, occurred during the second week postpartum in a few postnatal segment females of the 20 and 60 mg/kg/day groups. Mean negative geotaxis performance was delayed slightly, but mean progeny survival and body weights were not affected. Although after weaning the F1 offspring from the treatment-derived groups tended to weigh more than controls and to perform more effectively in the active avoidance task, these findings were attributed to unusually low values obtained in the control group. Startle amplitudes were increased significantly in the males from the 60 mg/kg/day treatment-derived group. These dose-related maternal and developmental findings were all consistent with the mixed D1/D2 agonist properties of pergolide mesylate, and suggest that only very high doses may result in persistent effects on the developing central dopaminergic systems. PMID- 1886540 TI - The teratogenic effects of nicotine in vitro in rats: a light and electron microscope study. AB - Cigarette smoking in pregnant women has been shown to lead to intrauterine growth retardation and fetal death, and possibly also to neural dysmorphology and long term learning deficits in the offspring. Because the teratogenic agent in cigarette smoke remains controversial, the present study on rat embryos in culture examined specifically whether nicotine can cause neural dysmorphology and, hence, act as a nervous system teratogen. This in vitro study confirmed previous reports in utero that nicotine leads to growth retardation, and, in addition, demonstrated that development of the nervous system, particularly the forebrain, as well as the branchial arches was impaired, possibly leading to microcephaly and cleft palate respectively in term fetuses. Cellular disruption and necrosis occurred in the neuroepithelium and underlying mesenchyme, with the effect being dose dependent. Ultrastructurally, there was severe disruption of cell and organelle membranes, with many healthy cells containing engulfed, whole condensed or remnants of dead cells. This study demonstrates that nicotine acts as a nervous system teratogen leading to gross and cellular dysmorphology. Suggested mechanisms for nicotine action include the possibility that the highly lipid soluble teratogen may exert its effects directly on the membranes or indirectly through oxidative membrane damage. PMID- 1886541 TI - Hyperactivity and spatial maze learning impairment of adult rats with temporary neonatal hypothyroidism. AB - Temporary hypothyroidism was induced in neonatal rats by 0.02% propylthiouracil (PTU) administration to lactating dams during days 0-19 after delivery, and its effects on the behavior and learning of their male offspring were examined. The serum T4 (thyroxine) level was returned to normal around 1 week after the last PTU administration, but the body weight gain was still depressed. The open field and Biel water maze tests at the age of 6 weeks showed an increased number of ambulations and an increase in errors with prolonged swimming time in the PTU rats. The radial arm maze test started at 13 weeks revealed that the PTU animals required more trials until they showed the first well-performed trial. The total number of choices was also larger, with less correct choices, and treatment effects on the response distribution and pattern were significant. Thus, the rats, which had suffered from temporary hypothyroidism in the neonatal period, showed hyperactivity and irreversible impairment in maze learning. These results suggest an involvement of temporary neonatal hypothyroidism in hippocampal dysfunction. PMID- 1886542 TI - Developmental toxicity evaluation of oral aluminum in rats: influence of citrate. AB - To evaluate the influence of citrate on the potential developmental toxicity of high doses of aluminum (133 mg/kg/day), three groups of pregnant Sprague-Dawley rats were given by gavage aluminum hydroxide (384 mg/kg/day), aluminum citrate (1064 mg/kg/day), or aluminum hydroxide (384 mg/kg/day) concurrent with citric acid (62 mg/kg/day) on gestational days 6 through 15. Control animals received distilled water. At termination on gestation day 20, live fetuses were examined for external, visceral, and skeletal alterations. There were no significant differences between controls and Al-treated rats on pre- or postimplantation loss, number of live fetuses per litter, or sex ratio. Fetal body weight was significantly reduced in the group treated with Al(OH)3 and citric acid. Although no increases in the incidence of malformations were observed, the incidence of skeletal variations was significantly increased in the group given Al(OH)3 concurrent with citric acid. In summary, although the administration of citric acid did not modify the lack of embryotoxicity and teratogenicity of Al(OH)3 in rats, some signs of maternal toxicity and fetotoxicity could be observed in this group. PMID- 1886543 TI - Prenatal marijuana use and neonatal outcome. AB - In a longitudinal study of marijuana and other substance use during pregnancy, women were interviewed at each trimester of pregnancy. Growth parameters, morphological abnormalities and gestational age were assessed for the 519 liveborn singletons. There were few significant effects of marijuana use during pregnancy on birth weight, head or chest circumference, gestational age, or growth retardation after adjustment for covariates using a regression model for analysis. There was a small but significant negative effect of marijuana use during the first two months of pregnancy on birth length and a positive effect of marijuana use during the third trimester on birth weight. PMID- 1886544 TI - Cocaine treatment in neonatal rats affects the adult behavioral response to amphetamine. AB - This study investigated whether exposure to cocaine during critical periods of brain development alters the motor stimulating effects of amphetamine given in adulthood. Female rats received 50 mg/kg/day cocaine HCl SC or vehicle during either postnatal days 1-10 or 11-20. At 60-65 days of age, activity counts were collected over a 15-min baseline period. Subjects then received one of 3 doses (0, 0.1, 0.25 mg/kg) of d-amphetamine sulfate SC followed by a 90-min period of activity monitoring. Adult activity in 1-10-day cocaine-treated rats was different from vehicle-treated rats in response to 0.1 mg/kg amphetamine only. Adult activity in 11-20-day cocaine-treated rats was different from vehicle treated rats in response to 0.25 mg/kg only. The observed differences represented an increase and decrease in activity, respectively. These alterations in amphetamine response may be related to the observed alterations in D-1 receptor concentrations as well as the altered rates of brain glucose metabolism we have observed in adult rats neonatally exposed to cocaine. PMID- 1886545 TI - Oxygen radicals: common mediators of neurotoxicity. AB - The inherent biochemical, anatomical and physiological characteristics of the brain make it especially vulnerable to insult. Specifically, some of these characteristics such as myelin and a high energy requirement provide for the introduction of free radical-induced insult. Recently, the biochemistry of free radicals has received considerable attention. It also has become increasingly apparent that many drug and chemical-induced toxicities may be evoked via free radicals and oxidative stress. Major points addressed in this work are the regulation of neural free radical generation by antioxidants and protective enzymes, xenobiotic-induced disruption of cerebral redox status, and specific examples of neurotoxic agent-induced alterations in free radical production as measured by the fluorescent probe dichlorofluorescein. This article considers the thesis that free radical mechanisms may contribute significantly to the properties of several diverse neurotoxic agents and proposes that excess production of free radicals may be common phenomena of neurotoxicity. PMID- 1886546 TI - Cocaine effects on fetal development: a comparison of clinical and animal research findings. AB - The clinical and animal literature describing the effects of cocaine use during pregnancy is reviewed. The difficulties associated with studying populations using illicit drugs during pregnancy and the multiple risk factors present in cocaine-using pregnant women limit the strength of the drug-associated effects. Nevertheless, cocaine use during pregnancy is associated with a significant number of obstetrical complications, small for gestational age infants and neurobehavioral abnormalities. In animal studies, only the neurobehavioral abnormalities could be demonstrated following the administration of non-toxic doses of cocaine. Furthermore, animal studies indicate that neurochemical changes, including those identified in the neuroendocrine axis, persist into adulthood. PMID- 1886547 TI - Program components of a comprehensive integrated care system for serious mentally ill patients with substance disorders. PMID- 1886548 TI - Dual diagnosis of major mental illness and substance disorder: an overview. AB - Dual diagnosis of severe mental illness and substance disorder is a frequent and difficult challenge to the mental health and substance abuse systems. This chapter reviews the dual diagnosis problem and introduces the chapters that follow. PMID- 1886549 TI - Assessment of comorbid psychiatric illness and substance disorders. PMID- 1886551 TI - An integrated treatment approach for severely mentally ill individuals with substance disorders. PMID- 1886550 TI - New Hampshire's specialized services for the dually diagnosed. AB - New Hampshire's specialized dual diagnosis services include continuous treatment teams and substance abuse treatment groups within each mental health center. These services are embedded in an extensive system of care for the dually diagnosed. PMID- 1886552 TI - Modifying the therapeutic community for the mentally ill substance abuser. PMID- 1886553 TI - Contrasting integrated and linkage models of treatment for homeless, dually diagnosed adults. PMID- 1886554 TI - Preventing neonatal hepatitis B virus infection. PMID- 1886555 TI - Incidence of hypoxemia associated with caregiving in premature infants. PMID- 1886556 TI - Pneumothorax in the newborn. AB - Air leak syndromes, and pneumothorax in particular, are a common occurrence in the NICU. Careful nursing assessment, monitoring, and management strategies offer the infant with pneumothorax his best hope. PMID- 1886558 TI - Developing a successful acuity billing system for intermediate nursery services. PMID- 1886557 TI - A case study: urea cycle disorder. AB - Early identification of symptoms consistent with a urea cycle disorder is crucial to ensure rapid initiation of therapy which, in turn, promotes the best possible prognosis for the newborn. Acute management may include the technological interventions of exchange transfusion, peritoneal dialysis or hemodialysis, prevention and treatment of seizures, prevention and/or treatment of increased intracranial pressure, and complex nutritional support with amino acids and/or essential enzymes. Long-term nursing management will also include identifying and providing supports for the family, promoting the integration of the infant into the family, and promoting infant growth and development. PMID- 1886559 TI - California magazines lose tax-exempt status. PMID- 1886560 TI - Nurse participation in ethical decision making in the neonatal intensive care unit. PMID- 1886561 TI - Broadening the focus of neonatal nursing. PMID- 1886562 TI - "United States Maternal and Child Health Services, Part I: Right or Privilege". PMID- 1886563 TI - Teaching parents in the NICU. PMID- 1886564 TI - Attempted suicide among high school students--United States, 1990. AB - Suicide rates for adolescents 15-19 years of age have quadrupled from 2.7 per 100,000 in 1950 to 11.3 in 1988 (1,2). Data from earlier decades are not available to assess similar trends in rates of attempted suicide in this population. Attempted suicide is a potentially lethal health event, a risk factor for future completed suicide, and a potential indicator of other health problems such as substance abuse, depression, or adjustment and stress reactions (3). This report examines self-reported data to estimate the annual prevalence of suicidal thoughts and behaviors among U.S. high school students. PMID- 1886565 TI - Mycobacterium haemophilum infections--New York City metropolitan area, 1990-1991. AB - During September 1990-March 1991, clinicians at a New York City (NYC) hospital diagnosed Mycobacterium haemophilum infections in four patients. Two cases occurred in persons with acquired immunodeficiency syndrome (AIDS), and two occurred in persons who had received bone marrow transplants and were on therapy to prevent a graft-versus-host reaction. In April 1991, three additional M. haemophilum infections in persons with AIDS were identified in the NYC area. Because M. haemophilum infection rarely has been recognized, intensive case finding was initiated in NYC as a result of these reports. PMID- 1886566 TI - Infant mortality--United States, 1988. AB - In 1988, 38,910 infants less than 1 year of age died in the United States, 502 fewer than in 1987. The infant mortality rate of 10.0 infant deaths per 1000 live births was the lowest final rate ever recorded; the rate was 10.1 in 1987. This report summarizes final 1988 infant mortality data based on information from death certificates compiled by CDC's National Center for Health Statistics' Vital Statistics System (1) and compares findings with those for 1987. PMID- 1886567 TI - [Antitumor effect of LPS immobilized beads]. AB - The anticancer effects of lipopolysaccharide (LPS) have been investigated, but its strong toxicity has made it difficult to utilize. In order to induce the anticancer effect without toxicity, LPS and its components were immobilized to polystyrene beads. Spleen cells from C3H/HeN mice and SD rats were activated by contact stimulation with immobilized beads. Cytotoxicity tests were measured by 51Cr release assay. Spleen cells stimulated by beads immobilizing a portion of the components constituting LPS led to little cytotoxicity. Spleen cells stimulated by E. coli LPS immobilized beads led to strong cytotoxicity in the murine system. On the other hand, in the SD rat system, cells stimulated with Salmonella LPS immobilized beads led to more stronger cytotoxicity than that of lymphokine activated killer (LAK) cells. These activities were enhanced by culturing within 48 to 72 hours after stimulation. Activated spleen cells were injected into the tumor-bearing mice intralesionally, and suppression of tumor growth and survival elongation of the mice were recognized. Activated cells were injected intravenously into the metastatic lung tumor-bearing rats, and lung metastasis almost vanished. LPS immobilized beads exhibited antitumor effects, and it was considered LPS immobilized beads induced killer cells through cytokines and proper immobilized LPS was different according to the species of animals. PMID- 1886568 TI - [Magnetic resonance (MR) imaging for the detection of the invasion into neighboring structures in esophageal cancers]. AB - In 104 patients with esophageal cancers, magnetic resonance (MR) imaging was performed to detect the invasion to aorta and tracheobronchial tree. Relatively short TR images (TR 300 or 40 msec) were best for depiction of esophageal cancers and neighboring structures. The detectability of esophageal cancer was 0% in cases of muscularis mucosa invasion, 50% in cases of submucosa invasion, and 75% in cases of muscularis propria invasion. In more invaded cases, all cases were detectable. Aortic invasion was evaluated according to the extent of contact and its consecutiveness between the esophagus and aorta; if contact more than 1/4 circumference was seen more than three contiguous slices, aortic invasion was diagnosed as positive. The accuracy rate of this criterion was 96.6%. Tracheobronchial invasion was evaluated according to the deformities of the trachea and bronchi by contiguous cancers those were classified into four types. It was determined that convex type (Type I) and flat type (Type II) were negative and concave type (Type III) and displaced type (Type IV) were positive. The accuracy rates of this criteria were 95% in the trachea and 87.7% in the bronchi. MRI is useful for the detecting of local invasion of esophageal cancer. PMID- 1886569 TI - [Experimental study of the effect of bile juice on the remnant gastric cancer development]. AB - Experimental studies were performed to investigate the role, if any, of bile reflux in cancer development in the stomach. A 20% solution of human bile juice and 50 micrograms/ml of the known carcinogenic MNNG were given perorally and heterochronically to male Wistar rat, and the incidence of carcinoma in the gastric gland of the rat was studied. The animals were divided into 4 groups: Group I, to which only MNNG was given. Group II, to which human bile juice and then MNNG were administered. Group III, to which MNNG and then human bile juice were administered. And Group IV, to which only human bile juice was given. The incidence of cancer was 37.5% (3/8) in Group II, 25% (2/8) in Group III, and 0% in Group I (0/12) and IV (0/12). The gastric gland mucosa was histologically examined at various times and also by microautoradiography using 3H-TdR. The results suggested that a reverse flow of bile juice to the human remnant stomach may induce an increase in proliferative cells in the lacunar epithelia of the stomach mucosa and that a predisposed site would then be available for cancer development. PMID- 1886570 TI - [Experimental study on carcinogenesis in the vagotomized stomach]. AB - The susceptibility to cancer in the vagotomized stomach which was assigned either to selective vagotomy (SV) or selective proximal vagotomy (SPV) was studied by gastric carcinoma model of male Wistar rat on N-methyl-N'-nitro-N nitrosoguanidine (MNNG) administration. Predilection for cancer of the remnant stomach was also studied. Four groups of the rats submitted to either one of the SV, SPV, antrectomy (Billroth-I reconstruction) or control (simple laparotomy) group, were prepared. The techniques of SV and SPV in rat was originally developed. MNNG in drinking water was given as carcinogen. Gastric acid output, gastric stasis, serum gastrin levels together with the number and the invasiveness of the atypical glands those were recognized in the glandular stomach of rats were examined. The results were as follows: (1) the reduction rate of gastric acid output was the most conspicuous at antrectomy group followed by SV and SPV groups, (2) gastric stasis was observed in almost the same degree in SV and SPV groups, (3) serum gastrin level was the highest in SV group followed by SPV, control and antrectomy groups in this order and (4) the susceptibility to malignancy was significantly high at SV group but not high at SPV and antrectomy group as compared with control group. PMID- 1886571 TI - [Patients with high risk of hematogenous metastasis and recurrence in colorectal cancer: correlation with histopathologic variables and tumor markers, CEA and CA19-9, in peripheral and draining venous blood]. AB - Correlations of hematogenous metastasis with histopathologic variables, preoperative CEA and CA19-9 levels in peripheral (p) venous blood, and those in draining (d) venous blood were examined in 78 patients with colorectal cancer. Out of 10 histopathologic variables, location of venous invasion was most significantly correlated with hematogenous recurrence: the rate (11%) of v0 and/or sm-pm v(+) in 50 patients without the recurrence was significantly lower than that (89%) in 28 patients with the recurrence. On the other hand, the rate (68%) of ss-extra(+) in the latter was significantly higher than that (32%) of the former. The mean values (6 and 14 ng/ml) and positive rates (22 and 48%) greater than 5 ng/ml of p and d-CEA in 50 patients without the recurrence were significantly lower than those (14 and 189 ng/ml, 48 and 96%) in 28 patients with the recurrence. Patients with d-p CEA gradient greater than 5 ng/ml were found, respectively, in 34% of the former and 82% in the latter. The mean value (982 U/l) and positive rate (94%) greater than 37 U/ml of CA19-9 in peripheral blood of 28 patients with the recurrence were significantly higher than those (25 U/ml and 11%) of 50 patients without the recurrence. These results suggest that colorectal cancer patients with high risk of hematogenous metastasis and recurrence are the patients with ss-extra(+), the values of d-CEA, especially d-p CEA gradient, greater than 5 ng/ml and with p-CA19-9 value greater than 37 U/ml. PMID- 1886572 TI - [Mechanism of retardation of obstructive jaundice: pathological investigation of alteration in bile flow]. AB - The morphological and functional alterations of hepatocytes were investigated on autopsy cases of human obstructive jaundice and experimentally common bile duct ligated rats. The livers were morphologically observed by light and electron microscopes, and in order to make clear the mechanism of bile flow, horse radish peroxidase (HRP) was injected in male Wistar rats from the inferior mesenteric vein and administered in retrograde from the common bile duct. In the extrahepatic bile duct obstruction, bile canaliculi were dilated and canalicular microvilli were decreased in number and showed bleb formation, and pericanalicular filamentous structure formed thick network. Injected HRP as a tracer was not presented in the laminar and intercellular space of hepatocytes, and administered HRP in retrograde was presented in the intercellular space through tight junction from bile canaliculi and presented pericanalicular cytoplasmic vesicles. These results suggest that extrahepatic bile duct obstruction induces morphological change in pericanalicular regions and the functional abnormality in the membrane structure of hepatocytes may be persistent cholestasis. PMID- 1886573 TI - [Inhibition of hepatic DNA synthesis after partial hepatectomy in the rats with obstructive jaundice with special reference to the enhancement of hepatic protein synthesis]. AB - We studied the liver regeneration after partial (68%) hepatectomy in rats with obstructive jaundice followed by the relief of obstruction. Rats received bile duct ligation, then 5 or 14 days later choledocho-duodenostomy was performed. Partial hepatectomy was done at various intervals after the relief of obstruction. DNA synthesis of the regenerating liver, hepatic protein synthesis and mitochondrial swelling induced by exogenous phospholipase A2 (PLA2) were determined. Hepatic DNA synthesis was significantly inhibited in obstructive jaundiced rats compared to controls. While the inhibition disappeared 5 days after the relief of obstruction in 5-day-obstructed group, it was still detectable as late as 21 days after the drainage in 14-day-obstructed group. Hepatic protein synthesis was markedly increased by obstructive jaundice, and this increase continued until 10 days after drainage in 14-day-obstructed group. Partial hepatectomy also increased the hepatic protein synthesis significantly in normal rats, but failed to show any significant changes in obstructive jaundiced rats. Any difference could not be found in PLA2-induced hepatic mitochondrial swelling between obstructive jaundiced rats and normal rats. We concluded the preceding energy-requiring responses in obstructive jaundiced liver resulted in the reduction of hepatic DNA synthesis and in the lack of additional increase of hepatic protein synthesis as the responses to a further insult of partial hepatectomy. PMID- 1886574 TI - [Experimental study of partial arterialization of the portal vein on the dearterialized liver]. AB - The influence of hepatic arterial obstruction on the hepatic circulation and tissue metabolism was studied between animals with and without partial arterialization of the portal vein. Mongrel dogs were divided into these groups: a group in which the collaterals to the liver were obstructed and the hepatic artery was dissected (hepatic artery ligated group); two groups in which an extracorporeal femoral artery-portal vein shunt was produced, and blood was sent by a Biopump at a rate of 100 or 200 ml/min (100 ml/min and 200 ml/min portal arterialized groups). The hepatic artery ligated group showed CO2 accumulation and acidosis in hepatic venous blood, reduction of oxygen supply, increase of oxygen consumption and marked increase of GOT and GPT. In the portal arterialized groups, sufficient oxygenation of portal blood was noted, and the oxygen demand and supply and tissue metabolism were kept approximately normal. The optimum flow rate for partial arterialization of the portal vein seemed to be 100 ml/min. At the flow rate of 200 ml/min, the original portal blood was reduced, leading to portal hypertension and increase of GOT and GPT. These results indicate that partial arterialization of the portal vein effectively preserves the liver function during the operation and in the early period after dissection of the hepatic artery. PMID- 1886575 TI - [Experimental study on the characteristic features of sympathetic nervous system reactions in dogs with obstructive jaundice]. AB - Possible abnormalities in the sympathetic nervous system responsible for circulatory disturbances with obstructive jaundice were investigated by determining the reactions of the heart and peripheral blood vessels using alpha.beta receptor stimulants or blockers. Mongrel dogs were randomly assigned to three groups: untreated (UT) and sham-operated (SO) controls and 3-week-old bile duct ligated (BDL). Under anesthesia with Nembutal, circulatory parameters and blood catecholamine concentration were measured. In term of alpha- and beta adrenergic reactions, reactions in the sympathetic nervous system to alpha- and beta-receptor stimulants were examined. Mean arterial pressure (MAP) and heart rate were used as an alpha-adrenergic parameter and a beta-adrenergic parameter, respectively. The hemodynamic study in BDL group was characterized by a reduction in MAP (p less than 0.05), total peripheral resistance (p less than 0.005) and left ventricular stroke work (LVSW) (p less than 0.05) and by an increase in cardiac index (p less than 0.05). The blood norepinephrine concentration was significantly increased in jaundice (p less than 0.01). Reaction to the beta receptor stimulant was significantly decreased in BDL group. In response to the alpha-receptor stimulant, lower reactivity was found in some animals in BDL group in comparison to SO group. Taking this into consideration with the increase in blood norepinephrine and the decrease in LVSW, the presence of abnormalities particularly in the beta-adrenergic system (receptor, cardiac muscle etc.) in jaundice is suggested to be a characteristic feature of reactions in the sympathetic nervous system. Such abnormalities are speculated to be responsible for postoperative shock. PMID- 1886576 TI - [Role of carcinoembryonic antigen, carbohydrate antigen 19-9 and cytology of bile in diagnosis of biliary and pancreatic cancer]. AB - To evaluate the clinical value in diagnosis of biliary and pancreatic cancer carcinoembryonic antigen (CEA), carbohydrate antigen (CA19-9) and cytology in the bile were examined in 343 patients with benign biliary disease and 71 patients with biliary and pancreatic cancer. An abnormal CEA level was defined as a level of more than 500 ng/ml in the gallbladder bile and 40 ng/ml in the bile duct bile. Increased bile CEA levels were observed in 50.0% in 22 patients with bile duct cancer, 60.0% in 20 with gallbladder cancer and 23.8% in 21 with pancreas cancer. False positive rate in 343 patients with benign diseases was only 1.2%. Bile CA19-9 levels were measured in 195 patients with benign disease and 30 with malignancy. However, the overlap between the values of the 2 groups was too great for differentiation of malignancy from benign disease. The positive rates of bile cytology were 52.2% in 23 patients with bile duct cancer, 40.0% in 15 with gallbladder cancer and 27.3% in 22 with pancreatic cancer. The diagnostic accuracies of combined assessment of bile CEA and cytology were 68.0% in 25 patients with bile duct cancer, 77.3% in 22 with gallbladder cancer and 37.5% in 24 with pancreatic cancer. The sensitivity of this combined test was 60.6% (43/71), and the specificity was 98.8% (339/343). This combined test is considered to be reliable screening test especially for biliary cancer. PMID- 1886577 TI - [Blood flow analysis of aorto-coronary bypass graft using a Doppler catheter- with special reference to comparison of SVG with IMAG]. AB - Since June to December, 1988, 46 patients had aorto-coronary bypass grafting (CABG) to the left anterior descending artery. Fifteen patients among them were subjected to this study. In 8 cases the internal mammary artery (IMAG group) was used and in 7 cases the saphenous vein graft was chosen as a bypass material (SVG group). Mean periphery anastomotic portion was 2.3 +/- 0.5 places for each group. Within two months after operation, intra-graft flow velocity was measured using a Doppler catheter. Mean cross sectional areas of the graft were 13.3 +/- 8.4 mm2 in the SVG group and 6.0 +/- 1.2 mm2 in the IMAG group. Peak flow velocity in diastole in SVG group and IMAG group were 9.9 +/- 2.7 cm/sec and 15.9 +/- 8.9 cm/sec, respectively (p less than 0.05). Also flow velocity in SVG (6.7 +/- 1.8 cm/sec) was significantly (p less than 0.05) lower than that in IMAG (12.1 +/- 6.4 cm/sec) in systole. There were no significant differences in peak, mean and integrated D/S ratio between SVG and IMAG as follows, peak D/S ratio: 1.6 +/- 0.3 in SVG, 1.4 +/- 0.4 in IMAG, mean D/S ratio: 1.5 +/- 0.3 in SVG, 1.4 +/- 0.4 in IMAG, integrated D/S ratio: 2.0 +/- 0.4 in SVG, 2.7 +/- 0.9 in IMAG. It is concluded that no significant differences were demonstrated between SVG and IMAG as to the intra-graft flow velocity profile at least in 2 months after operation. PMID- 1886578 TI - [Similarity between internal thoracic artery and gastroepiploic artery graft: pharmacological point of view]. AB - The pharmacological responses of internal thoracic artery (ITA), gastroepiploic artery (GEA) and saphenous vein (SV) obtained from patients receiving coronary artery bypass grafting (CABG) were assessed by isometric contraction records. The concentration-response curves for ergonovine and serotonin showed the leftward shift in SV compared with ITA and GEA. The 50% effective dose values of SV for ergonovine and serotonin were significantly less than those of ITA and GEA. The concentration-response curves for phenylephrine were similar among three kinds of grafts. There were no significant differences in the 50% effective dose values for phenylephrine among them. The effect of 0.4% papaverine chloride on the free graft flow was assessed in 15 patients receiving CABG with mean body surface area of 1.62 +/- 0.12 M2. The free flow of ITA graft was 71 +/- 32 ml/min before intraluminal papaverine injection, and that increased to 112 +/- 41 ml/min after injection. The free flow of GEA graft was 82 +/- 39 ml/min before injection, and that also increased to 128 +/- 40 ml/min after injection. The patency rates at the mean 2.2 months after grafting were 98% in ITA, 93% in GEA, and 88% in SV. In conclusion, both GEA graft and ITA graft can be expected as an excellent conduit in myocardial revascularization. PMID- 1886579 TI - [Effects of syngeneic preserved blood cells on metastatic growth of the Lewis lung carcinoma]. AB - Each of B6C3HF1 mice was infused with stored syngeneic blood cells, fresh syngeneic blood cells, or saline, and then was injected intravenously with 1 x 10(6) Lewis lung carcinoma cells. Survival rate of each group declined in order of the saline group, the fresh-cell group, and the stored-cell group with a significant difference between all paired groups (p less than 0.001). When the number of metastases and 125I-Iododeoxyuridine uptake in the lungs and livers were compared between these groups, there were significant differences with greater number and uptake in the stored-cell group than the fresh-cell group or the saline group on day 15 through 17, and greater in the fresh-cell group than the saline group on day 23 and 24. In the second experiment, each mouse was inoculated subcutaneously with 1 x 10(5) tumor cells. Twenty-one days later, the subcutaneous tumors were removed, and the mice were infused with blood cells or saline immediately. The number of lung metastases of the stored-cell group was significantly larger than that of the fresh-cell group or the saline group on 9 and 11 days following tumor removal. In conclusion, the transfusion of the preserved syngeneic blood cells was considered to enhance both artificial and spontaneous metastasis of the Lewis lung carcinoma. PMID- 1886580 TI - [A retrospective study of ruptured abdominal aortic aneurysms--association with respiratory function and leukocytic granular elastase]. AB - Fifty-two cases of abdominal aortic aneurysms including common iliac aneurysms operated on during July, 1981 and December, 1989 have been studied. They were divided into the following three of elective operation (n = 34), impending rupture (n = 5), and ruptured (n = 13) groups. Cases with abdominal operations without aneurysms were randomly selected as the control group (n = 12). Overall operative mortality was 9.6%, consisted of 30.8% of the ruptured, 20.0% of the impending rupture and 0% of the elective operation groups. Respiratory functions including FEV1.0%, V75, V50, V25 and V25/Ht were significantly lowered in the ruptured group. PaO2 of the ruptured group was also significantly lowered in comparison with both the control and the elective operation groups. Leukocytic granular elastase, playing a role of destruction of the elastin component in the pulmonary alveoli and the aortic media, was increased in the patients with ruptured aortic aneurysms, though the difference was not significant. The data suggested the possibility of aneurysm rupture in case with elevated leukocytic granular elastase. Surgery for abdominal aortic aneurysm, even in cases with decreased pulmonary function, should be considered aggressively to elimination of ominous result of aneurysm rupture. PMID- 1886581 TI - [Effect of Euro-Collins' or UW solution on the early graft function following cadaveric kidney transplantation]. AB - From November 1985 to March 1990, 55 cadaveric kidney transplants were performed under cyclosporine therapy. All kidneys were harvested from non-heart beating donors and cold stored after being flushed with EC solution (Group I, n = 27) or UW solution (Group II, n = 28). Warm ischemic time (min) in groups I and II were 7.1 +/- 3.3 and 6.9 +/- 2.3, respectively. Cold ischemic times (hr) in groups I and II were 6.9 +/- 2.4 and 8.4 +/- 2.8, respectively. Mean numbers of days for postoperative dialysis were 14.0 +/- 7.9 in group I and 7.9 +/- 5.8 in group II (p less than 0.05). One-month creatinine (mg/dl) was 2.9 +/- 2.8 in group I and 1.75 +/- 1.0 in group II (NS). One-month graft survivals (%) in groups I and II were 81.4% and 92.8%, respectively. In conclusion, UW solution has provided beneficial effect of preservation on ischemic damaged kidney and appears to be method of choice in non-heart beating cadaveric kidney transplantation. PMID- 1886582 TI - [Case of primary aorto-jejunal fistula caused by gram-positive cocci]. AB - A 46 year-old man was transferred to our department with a pulsating abdominal mass and back pain. On arrival he suddenly developed hematemesis. CT suggested the presence of an infrarenal aortic aneurysm and the jejunum was filled with contrast medium. An emergency operation was done. We found an aorto-jejunal fistula at the branching point of the renal artery. We directly sutured the aortic wall laceration and the jejunum wall in two layers. Then we resected infrarenal pseudoaneurysm as completely as possible, with replacement by a Dacron Y-shaped prosthesis. Culture of the aortic wall showed gram-positive cocci, but the species could not be identified. Gram stain of the aortic wall also showed infection by gram-positive cocci. The patient is alive and well 3 months after surgery. PMID- 1886583 TI - [Reconstruction of femoral vein using ePTFE grafts]. AB - Rare cases of reconstruction of peripheral veins were reported. We experienced two patients with liposarcomas of the thigh in which the femoral vessels were resected with the tumor and reconstructed with ePTFE grafts. In a 51-year-old male, the left femoral vein was reconstructed with an ePTFE graft 6 mm in diameter and 11 cm in length; but the graft occluded early in the postoperative period. In another case, a 33-year-old male, the right femoral vein was reconstructed with a ringed ePTFE graft 8 mm in diameter and 9 cm in length, with an arterio-venous fistula. The graft maintained its patency for 7 months after surgery. PMID- 1886584 TI - [A case of surgical treatment of Budd-Chiari syndrome]. AB - A 37-year-old man was admitted to our hospital for evaluation and surgical treatment of Budd-Chiari syndrome. He underwent a radical operation (endovenectomy and patch dilatation) with femoro-femoral assist bypass. The inferior vena cava (IVC) showed narrowing just below the diaphragm, and its lumen was completely obliterated with fibrous tissue. The fibrous strand was partially resected, and the IVC was closed by Xeno-medica pericardial patch. The patient has been doing well after the operation. PMID- 1886585 TI - [Studies on the concentration of surgical stress-related cytokines in exudate from operative wound or cavity: preliminary report]. PMID- 1886586 TI - [Lymphangiographic investigation of lymphatic regeneration after orthotopic small intestinal transplantation. A preliminary study with mesenteric lymphangiography: preliminary report]. PMID- 1886587 TI - [Total pancreaticoduodenal transplantation with portal venous drainage in the rat: retroparatopic pancreaticoduodenal transplantation: preliminary report]. PMID- 1886588 TI - [Pylorus preserving gastrectomy for early gastric cancer: preliminary report]. PMID- 1886589 TI - [Organ preservation with the combination of vasopressin and catecholamine in brain dead donors]. AB - Brain dead donor can not be maintained the systemic circulation more than 48 hours despite rather large dosage of catecholamine. The combined administration of arginine vasopressin (ADH) and catecholamine (epinephrine or dopamine) succeeded in long-term circulatory maintenance after brain death. We examined the renal and hepatic function by the method of circulatory maintenance. Twenty brain dead patients were randomly separated into two groups. Ten patients were maintained the systemic blood pressure with ADH and epinephrine (Group E). And the other ten were maintained with ADH and dopamine (Group D). Circulation was maintained with a small dosage of catecholamine at least six days in all donors. Urine output was well controlled, and serum BUN and creatinine were normal for 14 days. Daily creatinine clearance was always normal in both groups. Serum GPT, cholinesterase and alkaliphosphatase were the same in both groups, but total bilirubin was lower in group D than in group E on the seventh day. The combination of ADH and catecholamine preserved the kidney and liver after brain death for more than a week. This method will be of great value in organ transplantation from brain dead organ donors. PMID- 1886591 TI - [Changes in cardiorespiratory function after radical esophagectomy by bilateral thoracotomy approach in dogs]. AB - Twenty eight dogs (10-16 kg) were anesthetized with pentobarbital sodium, buprenorphine and pancuronium bromide followed by endotracheal intubation in the supine position. Twenty eight dogs were divided into two groups. Group 1 (n = 14) underwent thoracic esophagectomy with regional lymph nodes dissection under the right thoracotomy. Group 2 (n = 14) underwent the same manner of group 1. And left thoracotomy was added in the 5th intercostal space to completely dissect the left side regional lymph nodes. During surgical procedure, lactated Ringer's solution (L-R) were administered, L-R and Dextran 40 were given for postoperative fluid therapy. Cardiac output (CO), pulmonary arterial pressure (PAP), pulmonary wedge pressure (PWP), mean arterial pressure (AP), heart rate (PR), extravascular lung water (EVLW), blood gas analysis, pulmonary shunt rate (Qs/Qt), lung resistance (RL), dynamic lung compliance (CL) and colloid osmotic pressure (COP) were measured at preoperative phase and 1, 3, 6, 12 hrs after surgery. Significant differences were found in the left ventricular stroke work index (LVSWI), RL and the dosage of L-R between these dogs in groups 1 and 2. From these results, extended radical esophagotomy by bilateral thoracotomy approach for clinical cases seems to be possible under the exact indication and intensive perioperative care. PMID- 1886590 TI - [5-FU concentration in the tissue of gastric cancer, and evaluation of cancer chemotherapy with angiotensin-II]. AB - A preferable route for administration of anti-cancer drugs together with angiotensin-II (AT-II) was examined by measuring the tissue concentration of drugs in resected specimens. Twenty five patients with gastric cancer were randomly divided into five groups, and 5-FU (250 mg) was given with or without AT II intraoperatively. Group A; i.v. 5-FU alone (n = 5), Group B; i.v. 5-FU with AT II (n = 5), Group C; i.a. 5-FU alone (n = 5), Group D; i.a. 5-FU with i.v. AT-II (n = 5) and Group E; i.a. 5-FU with AT-II (n = 5). 5-FU level in regional lymph nodes was statistically higher in Group D compared to other groups, while in tumor tissues it was markedly higher in Group E. The ratio of 5-FU level in tumor tissues to normal tissues (T/N) was higher in Groups D and E. In patients with advanced malignancies, response rates were 17% in i.v. anti-cancer drugs with AT II group, 41% in i.a. anti-cancer drugs with i.v. AT-II group and 24% in i.a. anti-cancer drugs with AT-II group. Median survival time for each group were 6.3 months, 9.6 months and 14.2 months, respectively. It is concluded that intra arterial infusion chemotherapy together with AT-II can be an effective treatment for advanced malignancies. PMID- 1886593 TI - [The expression of the blood related antigens in intestinal metaplasia of the stomach in gastric cancer]. AB - The monoclonal antibodies detecting blood group related antigens of the Lewis systems have been used to define the immunoanatomic distribution of these antigens within the normal gastric mucosa and in gastric cancer tissues. In this study we analysed the presence of these antigens in histologically intestinal metaplasia of the stomach by the immunoperoxidase method. In normal gastric mucosa, Lewisb was distinctly expressed in normal foveolar epithelia and Lewisa was present in foveolar epithelia in half of the cases. Lewisx and Lewisy were detected in deep gastric glands. In intestinal metaplasia, more pronounced expression of Lewisa and decreased expression of Lewisb were observed. Lewisx and Lewisy were absent in most specimens of intestinal metaplasia. These pattern of expression of Lewis antigens in intestinal metaplasia were very similar to those observed in well and moderately differentiated adenocarcinomas of the stomach. These results indicate that well and moderately differentiated adenocarcinomas of the stomach have very similar character with the intestinal metaplasia in terms of the Lewis blood group antigen expression. PMID- 1886592 TI - [Nuclear morphometric and DNA content analyses of cancer cells in superficial esophageal cancer with reference to lymph node metastasis]. AB - In 23 cases of surgically resected superficial esophageal cancer which was defined by Japanese Society for Esophageal Diseases, the nuclear area (NA), nuclear shape factor (NSF) and DNA content (DNA) of cancer cells were measured using an image analysis system, and, in 7 out of the 23 cases, biopsy specimens were examined in the same way as well. The results were analyzed and evaluated with respect to lymph node metastasis. The NA was significantly larger (p less than 0.01) and the DNA content value was significantly higher (p less than 0.05) in the tumors with lymph node metastasis than in those with no lymph node metastasis. By means of a linear discriminant analysis using NA and DNA as variables, z = 0.238 X NA + 0.475 X DNA - 11.9, existence of lymph node metastasis could be correctly presumed at 87%. No false discrimination was found on preoperative biopsy specimens in 7 cases in which the accuracy of the discriminant analysis could be confirmed by microscopic examination of the lymph nodes extirpated at operation for esophagectomy. Conclusively NA and DNA correlate significantly with existence of lymph node metastasis in the patients with superficial esophageal cancer, and might be useful for preoperative predicting whether or not lymph node metastasis exists. PMID- 1886594 TI - [Study of para-aortic lymph node metastasis for advanced gastric cancer on consecutive lymph node slices]. AB - Para-aortic lymph nodes (No. 16) from 21 patients with advanced gastric cancer who underwent extensive lymph node dissection, were sliced consecutively at intervals of 50 mu to study minute metastasis of No. 16 lymph nodes. Twenty-six of 30 metastatic lymph nodes had minute involvement, in which carcinoma cells were detected in marginal sinus of lymph node, microscopically. The rate of the metastases to No. 16 lymph nodes was 19% among N0-3 cases by conventional method (not consecutive slices). On the contrary, the percentage of metastasis to No. 16 lymph nodes by consecutive slices was 33% among N0-3 cases. Therefore, No. 16 nodes are involved in metastasis at high rate at operation and the extensive lymph node dissection including No. 16 nodes (R4) will be recommended to prevent lymph node recurrence caused by such a minute metastasis. PMID- 1886595 TI - [Liver tissue pH measurement can predict survival in rats undergoing normothermic ischemias]. AB - The purpose of this study was to evaluate the usefulness of pH measurement of the liver for the prediction of survival after normothermic hepatic ischemia. Liver ischemia was induced in rats with cirrhosis and normal liver by cross-clamping of the portal vein and hepatic artery, bypassing the portal blood to the jugular vein through a shunt tube. The ischemic time periods were selected arbitrarily from 15 to 95 minutes. Preischemic liver function test was assessed by indocyanine green dye. I measured liver tissue pH continuously during the ischemic period. In addition, levels of adenosine triphosphate (ATP) of the hepatic tissue was determined every ten minutes after ischemia by HPLC and energy charge was calculated. There was a significant positive correlation between the postischemic change of the liver tissue pH and that of energy charge. A discriminant analysis yielded an equation predictive of survival: Y = 7.2 *delta pH10 + 27.15 *KICG - 0.07 *ischemic time - (Y greater than or equal to 0; survivors, Y less than 0; nonsurvivors, delta pH10; preischemic pH - pH at 10 minutes after ischemia). The equation predicted survival with 77.8% accuracy. I conclude that liver tissue pH reflects energy charge of the liver during the ischemic period and pH measurement can predict survival with high accuracy in rats undergoing normothermic ischemia. PMID- 1886596 TI - [Relationship between gastric emptying and G.I. symptoms after direct operations for esophageal varices: using double isotope method]. AB - Gastric emptying of mixed solid and liquid meals was studied in 34 subjects (5 normal young males, 6 preoperative patients and 23 patients after direct operations for esophageal varices), using double isotope method. Operative procedures were trans-abdominal esophageal transections in 16 patients and Hassab's operations in 7 patients. As an average, gastric emptying of postoperative patients doesn't differ so much from those of two other groups. However, postoperative gastric emptying scattered widely from rapid to slow, especially in solid meal. Furthermore, postoperative gastric emptying had relations with postoperative gastrointestinal symptoms (dumping syndrome, epigastric fullness, diarrhea, body weight loss and meal volume) in direct operations for esophageal varices. There was no significant relationship between their gastric emptying and background factors (diseases, Child's classification and postoperative period). This study suggests that some factors of operative procedures might affect and determine the postoperative gastric emptying of each patient. In conclusion, some remedy of operative procedures may decrease the postoperative G.I. symptoms after direct operations for esophageal varices. PMID- 1886597 TI - [Coronary artery bypass grafting combined with operation for non-cardiac disease]. AB - During the last two years and six months, ten patients underwent operation for both coronary artery disease and non-cardiac surgery. There were six patients with vascular disease, three with gastric cancer and one with cholelithiasis. Six patients had simultaneous operation of both coronary artery bypass grafting (CABG) and non-cardiac surgery, and four underwent non-cardiac surgery mean of 105 days after CABG. The number of significant lesions of coronary artery in patients with simultaneous or two-staged operation was 2.2 +/- 0.8 or 2.8 +/- 0.5 per patient, respectively. The operative time in patients with simultaneous operation was 361 +/- 49 minutes. However, in patients with staged operation the time for cardiac surgery was 380 +/- 36 minutes and the time for non-cardiac operation was 388 +/- 83 minutes. There were no patients with complications after either cardiac or non-cardiac operation. In patients having surgical indications for both coronary artery and non-cardiac diseases, CABG should be performed prior to the non-cardiac surgery. In patients with normal cardiac function and sufficient operative time after CABG, concomitant operation seemed to be recommended. In case with advanced malignant disease or incompetent cardiac function, staged operation would be selected for good surgical result. PMID- 1886598 TI - [Trans-sternal bilateral thoracotomy for bilateral lung lesions]. AB - The trans-sternal bilateral thoracotomy had been used widely in the early days of cardiac surgery, but since the 1960's the median sternotomy has played a great part in open heart surgery. Recently, the simultaneous bilateral thoracotomy has been used for bilateral lung lesions such as bilateral giant bullae, bilateral pneumothoraces and bilateral metastatic lung tumors. Since 1965 we have performed 6 operations using trans-sternal bilateral thoracotomy for several bilateral lung lesions. The diseases which led to the use of the trans-sternal bilateral thoracotomy technique were 2 cases of bilateral simultaneous pneumothoraces and 4 cases of bilateral lung metastatic tumors. The ages of the patients ranged from 17 to 45 years old. The operative blood loss was between 100 and 810 gm. No case showed postoperative respiratory distress or severe thoracic pain. It would like to be pointed out that the trans-sternal bilateral thoracotomy is the most ideal approach for the multiple bilateral lung metastatic lesions which often invade the chest wall or diaphragm. PMID- 1886599 TI - [De-endothelialization and re-endothelialization in autogenous vein grafts- fundamental and clinical study]. AB - Preparation for preserving endothelial cells (ECs) of autogenous vein grafts (AVGs) and the process of de-endothelialization (de-E) and re-endothelialization (re-E) were studied. Jugular veins (n = 31) from mongrel dogs were immersed in saline solution (SS), heparinized blood (HB), and other three kinds of solution. Then jugular veins (n = 26) immersed in SS for 3 hours, were used for AVGs to the abdominal aorta. Intimal changes were observed by scanning electron microscopy. ECs showed irreversible changes about 60 minutes after immersion in SS and about 150 minutes in HB. Eleven (92%) of 12 graft specimens within 1 day after implantation showed wide areas of de-E, while ECs on the venous valve were satisfactorily preserved in 6 (55%) of 11 valves. Re-E was observed predominantly around the valve from 3 days after implantation, and completed within 3 weeks. Clinically, specimens in 35 AVGs were collected before anastomosis. Severe EC damage was observed in 23 (66%) of them. Long-term observation revealed graft stenosis in 2 due to intimal hyperplasia (IH) in grafts with severely damaged EC. These results suggest that venous valves are an important source of re-E, and that the preservation of ECs in graft preparation is an important factor to prevent IH. PMID- 1886600 TI - [A case report of esophageal liposarcoma]. AB - We report the first case of esophageal liposarcoma in Japan. A 46-year-old female was admitted to our hospital with chief complaint of protruding tumor out of the mouth. She had two episodes of protruding tumor after nausea in last 6 months. Barium swallow showed a large polypoid lesion of approximately 16cm in length with a stalk. By endoscopic examination, it was the polyp originated from the anterior wall of the cervical esophagus. It was covered with intact squamous epithelia, which had slight redness and erosion in the apex. Under general anesthesia the tumor was cut off at the base through the oral cavity. Specimen was 11 x 4 x 3cm in size and had yellowish cut surface. Histologically, the tumor composed of mature adipocytes and many atypical lipoblasts with spider web shaped cytoplasm. We diagnosed this tumor as well differentiated liposarcoma. PMID- 1886602 TI - [The prognosis of segmental type of primary sclerosing cholangitis--a prognostic study of the cases]. AB - Our review of the cases of segmental primary sclerosing cholangitis (PSC) in Japanese literature has found nineteen cases, of which our own case in 1976 has been in good health for fifteen years and three months after resection. The prognostic study was possible in sixteen cases. In twelve cases the lesions were resected. Ten of twelve are found in good health, the average length of survival being nine years and one month. There are two cases of death and the causes are unknown. The unresected cases (4 out of 16) are all dead. It is concluded that the prognosis of segmental PSC is good if the lesion is resected. PMID- 1886601 TI - [A case of gas gangrene following operation of cervical esophageal carcinoma]. AB - A 74-year-old woman underwent surgery for cervical esophageal carcinoma. After operation, she had abdominal distension, high fever, and suddenly fell into shock and died. Autopsy revealed necrosis and multiple gas blebs in the entire digestive tract and liver. Direct smear specimens Gram-stained disclosed clostridium septicum and the cause of death was found to be gas gangrene. This is the first of clostridium infection localized in the digestive tract and liver after operation. Abdominal radiogram showed massive gas in the intestine, intramural bowel gas and gas in the portal vein, and these are very suggestive of gas gangrene of the intestinal tract. PMID- 1886603 TI - [An experimental study of the effects of M phi and NK cells on wound healing.: preliminary report]. PMID- 1886604 TI - Reversible inactivation of a transgene in Arabidopsis thaliana. AB - Fifty percent of Arabidopsis thaliana plants transgenic for a hygromycin resistance gene failed to transmit the resistance phenotype to the progeny. The complete transgene was, however, inherited in all cases according to Mendelian laws as observed by Southern analysis. This discrepancy between genotype and phenotype was the result of a reduced level of transcript in the sensitive transformants. The gene inactivation occurred in plants with multicopy integration of the foreign DNA. No definite correlation was found between gene inactivity and methylation of cytidine residues in the transgene sequence. Explants from several sensitive transformed plants regained a low level of hygromycin resistance on callus induction medium. Subsequent generations obtained by self-pollination were sensitive. In contrast, spontaneous restoration of hygromycin tolerance was observed in seedlings originating from out-crosses with wild-type plants or a different sensitive transformant. A reduction of the copy number was not a prerequisite for spontaneous reactivation. The resistance was often lost again in the next generation. Inactivation and reactivation of the transgene are therefore reversible. PMID- 1886605 TI - Physical linkage and transcriptional orientation of the tdc operon on the Escherichia coli chromosome. AB - The physical and genetic structure of 37 kilobases of DNA encompassing the tdc region at 68.3 min of the Escherichia coli chromosome was determined by DNA sequence analysis and restriction mapping. Re-examination of new data concerning the direction of transcription of the tdc operon revealed that in strain W3110 the tdc region is located on a transposable segment of DNA. PMID- 1886607 TI - Variation in electrophoretic karyotype between strains of Septoria nodorum. AB - The electrophoretic karyotype of 11 strains of the phytopathogenic fungus Septoria nodorum has been established by pulsed field gel electrophoresis with the CHEF DRII system. Each strain had a similar overall karyotype with 14-19 chromosomes being resolved in the size interval between approximately 0.5 and 3.5 megabase pairs (Mb). However, there were clear differences in karyotype both between and within groups of strains adapted to wheat or to barley. Considerable karyotype variation was apparent even among 6 wheat-adapted strains isolated from the same population. Only 2 strains possessed identical karyotypes; these were isolated from the same leaf and were heterokaryon-compatible and are probably independent isolates of the same clone. PMID- 1886608 TI - Nucleotide sequence of a new class A beta-lactamase gene from the chromosome of Yersinia enterocolitica: implications for the evolution of class A beta lactamases. AB - The nucleotide sequence has been determined of a 1400 bp fragment from the chromosome of Yersinia enterocolitica containing the gene for beta-lactamase I. An ORF of 882 bp was identified, which could code for a polypeptide of 294 amino acids, closely related to other beta-lactamases of molecular class A. Amino acids 1-30 could constitute a signal peptide. The mature protein would be 264 amino acids long with a calculated pI of 6.2. Alignment of the amino acid sequence of the class A beta-lactamases suggested the existence of two subgroups in the same class, and this is discussed in the context of the evolution of the enzymes. PMID- 1886606 TI - Mitochondrial inner membrane protease 1 of Saccharomyces cerevisiae shows sequence similarity to the Escherichia coli leader peptidase. AB - The nuclear yeast mutant pet ts2858 is defective in the removal of pre-sequences from the mitochondrially encoded cytochrome oxidase subunit II (COXII) and the processing intermediate of cytochrome b2 (Cytb2), a nuclear gene product. In order to identify the genetic lesion in this mutant we have cloned and characterized a DNA region which complements the pet ts2858 mutation. The DNA sequence revealed three open reading frames, one of which is responsible for the complementation. A 570 bp reading frame represents the structural gene PET2858, as demonstrated by in vitro mutagenesis, gene expression from a foreign promoter, and allelism tests. PET2858 encodes a 21.4 kDa protein, which is essential for growth on non-fermentable carbon sources and for the proteolytic processing of COXII and the Cytb2 intermediate. When the N-terminus of the PET2858 protein is fused to a reporter protein, the resulting hybrid molecule is imported into mitochondria. Interestingly, the N-terminal half of the deduced PET2858 protein exhibits 30.7% amino acid identity to the leader peptidase of Escherichia coli. These results suggest that PET2858 codes for a mitochondrial inner membrane protease (IMP1) or at least a subunit of it. This protease is involved in protein processing and export from the mitochondrial matrix. PMID- 1886609 TI - Sequence of the structural gene for granule-bound starch synthase of potato (Solanum tuberosum L.) and evidence for a single point deletion in the amf allele. AB - The genomic sequence of the potato gene for starch granule-bound starch synthase (GBSS; "waxy protein") has been determined for the wild-type allele of a monoploid genotype from which an amylose-free (amf) mutant was derived, and for the mutant part of the amf allele. Comparison of the wild-type sequence with a cDNA sequence from the literature and a newly isolated cDNA revealed the presence of 13 introns, the first of which is located in the untranslated leader. The promoter contains a G-box-like sequence. The deduced amino acid sequence of the precursor of GBSS shows a high degree of identity with monocot waxy protein sequences in the region corresponding to the mature form of the enzyme. The transit peptide of 77 amino acids, required for routing of the precursor to the plastids, shows much less identity with the transit peptides of the other waxy preproteins, but resembles the hydropathic distributions of these peptides. Alignment of the amino acid sequences of the four mature starch synthases with the Escherichia coli glgA gene product revealed the presence of at least three conserved boxes; there is no homology with previously proposed starch-binding domains of other enzymes involved in starch metabolism. We report the use of chimeric constructs with wild-type and amf sequences to localize, via complementation experiments, the region of the amf allele in which the mutation resides. Direct sequencing of polymerase chain reaction products confirmed that the amf mutation is a deletion of a single AT basepair in the region coding for the transit peptide.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1886611 TI - Two allelic genes responsible for vegetative incompatibility in the fungus Podospora anserina are not essential for cell viability. AB - Vegetative incompatibility is a lethal reaction that destroys the heterokaryotic cells formed by the fusion of hyphae of non-isogenic strains in many fungi. That incompatibility is genetically determined is well known but the function of the genes triggering this rapid cell death is not. The two allelic incompatibility genes, s and S, of the fungus Podospora anserina were characterized. Both encode 30 kDa polypeptides, which differ by 14 amino acids between the two genes. These two proteins are responsible for the incompatibility reaction that results when cells containing s and S genes fuse. Inactivation of the s or S gene by disruption suppresses incompatibility but does not affect the growth or the sexual cycle of the mutant strains. This suggests that these incompatibility genes have no essential function in the life cycle of the fungus. PMID- 1886610 TI - Post-transcriptional regulation in higher eukaryotes: the role of the reporter gene in controlling expression. AB - We have investigated whether reporter genes influence cytoplasmic regulation of gene expression in tobacco and Chinese hamster ovary (CHO) cells. Two genes, uidA encoding beta-glucuronidase (GUS) from Escherichia coli and Luc, encoding firefly luciferase (LUC), were used to analyze the ability of a cap, polyadenylated tail, and the 5'- and 3'-untranslated regions (UTR) from tobacco mosaic virus (TMV) to regulate expression. The regulation associated with the 5' cap structure and the TMV 5'-UTR, both of which enhance translational efficiency, was reporter gene independent. The poly(A) tail and the TMV 3'-UTR, which is functionally equivalent to a poly(A) tail, increase translational efficiency as well as mRNA stability. The regulation associated with these 3' ends was highly reporter gene dependent; their effect on GUS expression was almost an order of magnitude greater than that on LUC expression. In tobacco, the tenfold reporter gene effect on poly(A) tail or TMV 3'-UTR function could not be explained by a differential impact on mRNA stability; GUS and LUC mRNA half-life increased only twofold when either the poly(A) tail or TMV 3'-UTR was present. In CHO cells, however, GUS mRNA was stabilized to a greater extent by a poly(A) tail or the TMV 3'-UTR than was LUC mRNA. PMID- 1886612 TI - The GAM1/SNF2 gene of Saccharomyces cerevisiae encodes a highly charged nuclear protein required for transcription of the STA1 gene. AB - We have cloned and sequenced the GAM1 gene which is required for transcription of the STA1 gene encoding an extracellular glucoamylase in Saccharomyces cerevisiae var. diastaticus. Complementation tests indicated that GAM1 is the same gene as SNF2 which is required for derepression of the SUC2 gene encoding invertase. Accumulation of SNF2 RNA was not regulated by the GAM2 and GAM3 genes which are also required for STA1 expression. The SNF2 gene was predicted to encode a 194 kDa highly charged protein with a glutamine-rich tract. A bifunctional SNF2-lacZ fusion protein was shown by immunofluorescence microscopy to be localized to the nucleus, suggesting that the SNF2 protein is located in the nucleus. PMID- 1886613 TI - Direct genetic selection of a maize cDNA for dihydrodipicolinate synthase in an Escherichia coli dapA- auxotroph. AB - Dihydrodipicolinate synthase (DHPS; EC 4.2.1.52) is the first committed enzyme in the lysine branch of the aspartate-derived amino acid biosynthesis pathway and is common to bacteria and plants. Due to feedback inhibition by lysine, DHPS serves in a regulatory role for this pathway in plant metabolism. To elucidate the molecular genetic characteristics of DHPS, we isolated a putative full-length cDNA clone for maize DHPS by direct genetic selection in an Escherichia coli dapA auxotroph. The maize DHPS activity expressed in the complemented E. coli auxotroph showed the lysine inhibition characteristics of purified maize DHPS, indicating that the cDNA encoded sequences for both the catalytic function and regulatory properties of the enzyme. The N-terminal amino acid sequence of purified maize DHPS was determined by direct sequencing and showed homology to a sequence within the cDNA, indicating that the clone contained the entire coding region for a mature polypeptide of 326 amino acids plus a 54 amino acid transit peptide sequence. The molecular weight of 35,854, predicted from the deduced amino acid sequence, was similar to the 38,000 Mr determined by SDS polyacrylamide gel electrophoresis (SDS-PAGE) for the purified enzyme from maize. DHPS mRNAs complementary to the cDNA were detected in RNA isolated from developing maize endosperm and embryo tissues. Southern blots indicated the presence of more than one genomic sequence homologous to DHPS per haploid maize genome. PMID- 1886614 TI - Novel mercury resistance determinants carried by IncJ plasmids pMERPH and R391. AB - HgCl2 resistance (Hgr) in a strain of Pseudomonas putrefaciens isolated from the River Mersey was identified as plasmid-borne by its transfer to Escherichia coli in conjugative matings. This plasmid, pMERPH, could not be isolated and was incompatible with the chromosomally integrated IncJ Hgr plasmid R391. pMERPH and R391 both express inducible, narrow-spectrum mercury resistance and detoxify HgCl2 by volatilization. The cloned mer determinants from pMERPH (pSP100) and R391 (pSP200) have very similar restriction maps and express identical polypeptide products. However, these features show distinct differences from those of the Tn501 family of mer determinants. pSP100 and pSP200 failed to hybridize at moderate stringency to merRTPA and merC probes from Tn501 and Tn21, respectively. We conclude that the IncJ mer determinants are only distantly related to that from Tn501 and its closely homologous relatives and that it identifies a novel sequence which is relatively rare in bacteria isolated from natural environments. PMID- 1886615 TI - cysB and cysE mutants of Escherichia coli K12 show increased resistance to novobiocin. AB - Mutations in the cysB and cysE genes of Escherichia coli K12 cause an increase in resistance to the gyrase inhibitor novobiocin but not to coumermycin, acriflavine and rifampicin. This unusual relationship was also observed among spontaneous novobiocin resistant (Novr) mutants: 10% of Novr mutants isolated on rich (LA) plates with novobiocin could not grow on minimal plates, and among those approximately half were cysB or cysE mutants. Further analyses demonstrated that cysB and cysE negative alleles neither interfere with transport of novobiocin nor affect DNA supercoiling. PMID- 1886616 TI - Sequence of a cellulase gene from the rumen anaerobe Ruminococcus flavefaciens 17. AB - A cellulase gene (endA) was isolated from a library of Ruminococcus flavefaciens strain 17 DNA fragments inserted in pUC13. The endA product showed activity against acid-swollen cellulose, carboxymethyl-cellulose, lichenan, cellopentaose and cellotetraose, but showed no activity against cellotriose or binding to avicel. Nucleotide sequencing indicated an encoded product of 455 amino acids which showed significant sequence similarity (ranging from 56% to 61%) with three endoglucanases from Ruminococcus albus, and with Clostridium thermocellum endoglucanase E. Little relatedness was found with a cellodextrinase previously isolated from R. flavefaciens FD1. PMID- 1886617 TI - Analysis of conserved domains identifies a unique structural feature of a chloroplast heat shock protein. PMID- 1886618 TI - An essential gene of Escherichia coli that has sequence similarity to a chloroplast gene of unknown function. AB - The dedB gene of Escherichia coli has sequence similarity to the zfpA gene of the chloroplast chromosome. The functions of dedB and zfpA are unknown. We constructed derivatives of temperature-sensitive polA strains into whose chromosomes a plasmid containing the disrupted dedB gene was integrated by homologous recombination. These strains contained normal and disrupted dedB genes in their chromosomes. We then selected plasmid-segregated strains and found no cells containing the disrupted dedB gene, indicating that disruption of the dedB gene was lethal in polA strains of E. coli. PMID- 1886619 TI - High-frequency transfer of linear DNA containing 5'-covalently linked terminal proteins: electroporation of bacteriophage PRD1 genome into Escherichia coli. AB - Using electroporation with the phage PRD1 genome, we set up a high-frequency DNA transfer system for a linear dsDNA molecule with 5'-covalently linked terminal proteins. The transfer was saturated when more than 100 ng of PRD1 genome was used. Electroporation efficiency was about four orders of magnitude higher than that obtained with transfection. Removal of the terminal protein abolished plaque formation, which could not be rescued by supplying the terminal protein or phage DNA polymerase or both in trans. PMID- 1886620 TI - Primary structure of a novel barley gene differentially expressed in immature aleurone layers. AB - As a direct approach to elucidate the molecular biology of barley aleurone cell development, we differentially screened an aleurone cDNA library made from poly(A)+ RNA of immature grains for clones representing transcripts present in the aleurone but not in the starchy endosperm. For one of these clones, B22E, which hybridies to a 0.7 kb transcript, Northern and in situ hybridization revealed that expression is under complex spatial, temporal and hormonal control in barley grains. cDNAs corresponding to B22E transcripts were isolated from aleurone/pericarp and embryo of developing grains, and from germinating scutella. Among these were the nearly full-length aleurone/pericarp clone pB22E.a16 (541 bp). cDNAs matching the sequence of this clone (type 1 transcript) were found for all tissues investigated. In addition, cDNAs with an extra 12 bp insertion (type 2 transcript) were obtained from germinating scutella. The two different transcripts can encode novel barley proteins of 115 and 119 amino acids, respectively. A gene designated B22EL8 was isolated and sequenced; it encodes the type 1 B22E transcript and contains two introns of 145 and 125 bp. Particle bombardment of barley aleurone with a B22EL8 promoter-GUS (beta-glucuronidase) construct demonstrates that the promoter (3 kb) is active in developing barley grains. The promoter is not, however, active in the seeds of tobacco plants transgenic for the B22EL8 gene, indicating the existence of sequences specific for monocots. A comparison of 1.4 kb of upstream sequence of B22E with the maize c1 promoter reveals a number of short, identical sequences which may be responsible for aleurone cell-specific gene transcription. PMID- 1886622 TI - [Psychopathology and follow-up of post-acute schizophrenia]. PMID- 1886621 TI - Cloning and expression in yeast of a cDNA clone encoding Aspergillus oryzae neutral protease II, a unique metalloprotease. AB - The neutral protease II (NpII) from Aspergillus oryzae is a zinc-containing metalloprotease with some unique properties. To elucidate its structure, we isolated a full-length cDNA clone for NpII. Sequence analysis reveals that NpII has a prepro region consisting of 175 amino acids preceding the mature region, which consists of 177 amino acids. As compared with other microbial metalloproteases, NpII is found to be unique in that it shares only a limited homology with them around two zinc ligand His residues and that the positions of the other zinc ligand (Glu) and the active site (His) cannot be established by homology. When a plasmid designed to express the prepro NpII cDNA was introduced into Saccharomyces cerevisiae and the transformant was cultured in YPD medium (2% glucose, 2% polypeptone, 1% yeast extract), it secreted a proNpII. However, in a culture of the same medium containing 0.2 mM ZnCl2, it secreted a mature NpII with a specific activity and N-terminus identical to those of native NpII. This observation suggests that either an autoproteolytic activity or a yeast protease effected the processing. PMID- 1886623 TI - Inflammatory bowel disease (2) PMID- 1886624 TI - Sucralfate. PMID- 1886625 TI - Breast-feeding in 1991. PMID- 1886626 TI - Circadian variation and cardiovascular disease. PMID- 1886627 TI - Left-handedness and life expectancy. PMID- 1886628 TI - Underdetection of substance abuse. PMID- 1886629 TI - Hydroxychloroquine in systemic lupus erythematosus. PMID- 1886630 TI - Lidoflazine in the treatment of comatose survivors of cardiac arrest. PMID- 1886631 TI - Exceptionally high serum IgM levels (case 18-1991) PMID- 1886632 TI - Penicillin-resistant pneumococcal meningitis in an HIV-infected man. PMID- 1886633 TI - Letting children observe deliveries. PMID- 1886634 TI - The transfer of alcohol to human milk. Effects on flavor and the infant's behavior. AB - BACKGROUND: The amount of alcohol ingested by a breast-fed infant is only a small fraction of that consumed by its mother, but even this small amount may have an effect on the infant. We investigated whether the ingestion of alcohol by a lactating woman altered the odor of her milk and whether exposure to a small amount of alcohol in the mother's milk had immediate effects on the behavior of the infant. METHODS: Twelve lactating women and their infants were tested on two days separated by an interval of one week. On each testing day, the mother expressed a small quantity of breast milk and then drank either orange juice or orange juice containing a small quantity of ethanol (0.3 g per kilogram of body weight). Additional milk samples were obtained at fixed intervals after the ingestion of the beverage and analyzed to determine their ethanol content. The samples were also evaluated by a panel of adults to determine whether any difference in the odor of the milk was detectable after alcohol ingestion. The infants were weighed before and after nursing to assess the amount of milk they ingested, and their behavior during breast-feeding was monitored by videotape. RESULTS: Short-term alcohol consumption by lactating women significantly and uniformly increased the perceived intensity of the odor of their milk as assessed by the panel; this increase in the intensity of the odor peaked 30 minutes to 1 hour after the alcohol was consumed and decreased thereafter. The alteration in the odor of the milk closely paralleled the changes in the concentration of ethanol in the milk (mean range, 0 to 6.9 mmol per liter [0 to 32 mg per deciliter]). The infants sucked more frequently during the first minute of feedings after their mothers had consumed alcohol (67.0 +/- 6.5 sucks, as compared with 58.4 +/- 5.9 sucks for feedings after the consumption of the nonalcoholic beverage; P less than 0.05), but they consumed significantly less milk (120.4 +/- 9.5 ml vs. 156.4 +/- 8.2 ml, P less than 0.001) during the testing sessions in which their mothers drank the alcoholic beverage. CONCLUSIONS: Although the mechanisms underlying this reduction in milk intake remain to be elucidated, this study shows that short-term alcohol consumption by nursing mothers has an immediate effect on the sensory characteristics (odor) of their milk and the feeding behavior of their infants. PMID- 1886635 TI - Circadian variation in vascular tone and its relation to alpha-sympathetic vasoconstrictor activity. AB - BACKGROUND: The frequency of several cardiovascular events, such as myocardial infarction, sudden death, and stroke, is increased during the early morning hours. There is also a similar circadian pattern in several physiologic variables, including blood pressure, suggesting that certain dynamic processes may contribute to the circadian distribution and onset of acute events. METHODS: To determine whether there are circadian variations in vascular tone and to investigate their underlying mechanisms, we measured blood flow and vascular resistance in the forearm and their responses to phentolamine (an alpha adrenergic-antagonist drug) and sodium nitroprusside (a direct vasodilator) in 12 normal subjects (7 men and 5 women; mean age [+/- SD], 44 +/- 9 years) at three different times of day (7 a.m., 2. p.m., and 9 p.m.). The drugs were infused into the brachial artery, and the responses were measured by strain-gauge plethysmography. RESULTS: The basal forearm vascular resistance was significantly higher, and the blood flow significantly lower, in the morning than in the afternoon and evening (mean vascular resistance, 31 +/- 8, 25 +/- 6, and 22 +/- 7 mm Hg per milliliter per minute per 100 ml of forearm volume, respectively; P less than 0.01). The vasodilator effect of phentolamine was also significantly greater in the morning (mean decrease in vascular resistance, 38 +/- 6 percent) than in the afternoon (26 +/- 6 percent) and evening (21 +/- 7 percent) (P less than 0.05). Consequently, there was no circadian variation in vascular resistance or blood flow after the infusion of this drug. In contrast, the vasodilation in response to sodium nitroprusside was similar at all three times of day. CONCLUSIONS: There is a circadian rhythm in basal vascular tone, due either partly or entirely to increased alpha-sympathetic vasoconstrictor activity during the morning. This variation may contribute to higher blood pressure and the increased incidence of cardiovascular events at this time of day. PMID- 1886636 TI - Paroxysmal nocturnal hemoglobinuria with onset in childhood and adolescence. AB - BACKGROUND: Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal hematologic disorder characterized by hemoglobinuria, thrombosis, infection, and a tendency toward bone marrow aplasia. Onset usually occurs in adulthood. Few children and adolescents with PNH have been described, and data on diagnosis, clinical course, and survival in young patients are unavailable. METHODS: We retrospectively reviewed clinical and laboratory data on all patients 21 years old or younger in whom PNH had been diagnosed at Duke University Medical Center from 1966 to 1991. RESULTS: Medical records and clinical follow-up data were available for 26 young patients. Although 50 percent of adult patients present with hemoglobinuria, only four of our patients (15 percent) presented with this feature. In contrast, 15 of our patients (58 percent) had moderate or severe bone marrow failure at presentation, as compared with about 25 percent of adults in cases from the literature; all 26 patients eventually had evidence of bone marrow dysfunction. Eight patients (31 percent) have died, with a median survival of 13.5 years since their initial symptoms. CONCLUSIONS: Children and adolescents with PNH have a greater prevalence of bone marrow failure than do adults with this disorder, and their morbidity and mortality are high. Bone marrow transplantation should be considered for selected young patients with PNH. PMID- 1886637 TI - Circulating and tissue endothelin immunoreactivity in advanced atherosclerosis. AB - BACKGROUND: Atherosclerosis is characterized by endothelial injury and the proliferation of arterial smooth-muscle cells. The latter may be a result of the release of growth factors from the vessel wall; such growth factors may include an endothelium-derived vasoconstrictor for peptide with mitogenic properties. We tested the hypothesis that plasma endothelin concentrations are elevated in persons with symptomatic atherosclerosis, independently of age. METHODS: We measured plasma endothelin levels in 100 normal subjects and in 40 patients with atherosclerosis predominantly of the following types: aortic and peripheral vascular disease (14 patients), renovascular disease (9 patients) coronary artery disease (9 patients), and carotid disease (8 patients). We also performed immunohistochemical staining for endothelin in the walls of atherosclerotic vessels. RESULTS: In the normal subjects, the mean (+/- SD) plasma endothelin concentration was 1.4 +/- 0.2 pmol per liter, with no correlation between age and plasma endothelin concentration (r = 0.13, P = 0.2). In the patients with symptomatic atherosclerosis, the mean plasma endothelin concentration was 3.2 +/- 1.2 pmol per liter (P less than 0.001), and there was a significant correlation between plasma endothelin and the number of sites of disease involvement (r = 0.89, P less than 0.001). In the immunohistochemical studies, endothelin-1-like immunoreactivity was observed in vascular smooth muscle as well as in endothelial cells. CONCLUSIONS: Endothelin may be a marker for arterial vascular disease. Whether it participates in the atherogenic process or is merely released from damaged endothelial cells is unclear. PMID- 1886638 TI - Concentrations of fumonisin B1 in feeds associated with animal health problems. AB - Ninety-eight samples of feeds associated with 44 cases of equine leukoencephalomalacia (ELEM) and 83 samples of feed associated with 42 cases of a porcine pulmonary edema syndrome (PPE) were analyzed for fumonisin B1 (FB1). For comparison purposes, 51 feed samples not associated with PPE or ELEM were also analyzed. Feed associated with ELEM contained FB1 ranging from less than 1 microgram/g to 126 micrograms/g with 75% of the cases having at least 1 sample above 10 micrograms/g. Feeds associated with PPE ranged from less than 1 microgram/g to 330 micrograms/g with 71% of the cases having at least 1 sample greater than 10 micrograms/g. Quantitation was by high performance liquid chromatography (HPLC)/fluorescence using the fluorescamine derivative with confirmation by thin layer chromatography (TLC) and/or gas chromatography/mass spectroscopy (GC/MS). PMID- 1886639 TI - Detection of antibody responses and delayed dermal hypersensitivity with Blastomyces dermatitidis yeast and mycelial lysate antigens. AB - Yeast cell lysate and mycelial lysate antigens prepared from one strain (T-58) of Blastomyces dermatitidis were evaluated with respect to the detection of antibodies and delayed dermal hypersensitivity. Comparable ELISA sensitivity values were evidenced with the two antigens when assayed against serum specimens from dogs with blastomycosis, sera from non-infected dogs residing in endemic and non-endemic areas for blastomycosis and sera from rabbits that were hyperimmunized with B. dermatitidis antigens. Specificity determinations with anti-Histoplasma capsulatum rabbit sera indicated that both reagents exhibited only minimal cross-reactivity; the mycelial antigen was slightly more specific than the yeast phase reagent. Similar sensitivity and specificity results were experienced when the two antigens were used to detect delayed dermal hypersensitivity in guinea pigs previously sensitized with B. dermatitidis or H. capsulatum. PMID- 1886640 TI - Overview: cryptococcosis in the patient with AIDS. AB - Cryptococcosis is currently the most common life threatening mycoses found in patients with the acquired immunodeficiency syndrome (AIDS). Extrapulmonary involvement is most frequently seen, especially in the central nervous system and skin. Clinical findings are non-specific, even in patients with meningitis. Threshold for diagnosis of this infection should be low, with serum cryptococcal antigens, blood, urine and sputum cultures for Cryptococcus neoformans performed in febrile AIDS patients. Lumbar puncture should also be performed if unexplained headaches are included in a patient's complaints. There is currently no consensus for the most appropriate treatment strategy and the role of oral azoles versus amphotericin B or amphotericin B with flucytosine remains a serious question in need of further controlled studies. Patients eligible for multicentered trials should be encouraged to participate. Therapy for others should be individualized. This review will address some of these issues. PMID- 1886641 TI - Pseudomicrodochium fusarioides sp. nov., isolated from human bronchial fluid. AB - A fungus from bronchial lavage fluid from a patient with pulmonary infiltration was isolated in pure culture and identified as a species of Pseudomicrodochium. It is compared and contrasted with other species of the genus, in particular P. suttonii, and formally described as P. fusarioides. PMID- 1886642 TI - In vitro proteinase production by Candida species. AB - A total of 290 Candida isolates from patients were investigated for in vitro proteinase production. Overall, sixty percent of these strains were found to be proteinase producers. Of the C. albicans strains, 81.4% of the significant isolates in contrast to 19.7% of nonsignificant isolates were proteinase producers, the difference being statistically significant (P less than 0.001). Amongst the different Candida species, the proteinase production was found not only in Candida albicans, but also in C. tropicalis, C. parapsilosis and C. glabrata. Thus this in vitro method of demonstration of proteinase may be a good adjunct to smear and culture examination in identifying pathogenic Candida species from anatomical sites where they can also be present as commensals. PMID- 1886643 TI - Electron microscopic study of conidia produced by the mycelium of Paracoccidioides brasiliensis. AB - The ultrastructure of asexual spores (conidia) produced by the mycelial form of Paracoccidioides brasiliensis was studied for the first time with transmission electron microscopy, using thin sections of aldehyde-osmium-fixed and epoxy-resin embedded samples. The various types of conidia observed in the sections correlated well with previous light-microscopic descriptions. These types were intercalary or apical conidia, depending on their location along the originating hyphae. As in previous studies they were characterized as arthroconidia, aleuriospores and sessile or pedunculate pyriform conidia. The sporogenous cells were clearly distinguished from hyphal cells by the thickness and appearance of their cell walls. Copious fibrillar material (glycocalyx) detected at the cell surface was stained with ruthenium red during the fixation process. Typical subcellular organelles (nucleus, nucleolus, mitochondria, ribosomes, etc) were found in most of the sections. It was concluded that the spores produced by the mycelial phase of P. brasiliensis possess all attributes of viable and physiologically competent eukaryotic cells. PMID- 1886644 TI - Sputum cytology in the diagnosis of pulmonary paracoccidioidomycosis. AB - The presence of Paracoccidioides brasiliensis was determined in sputum samples from 50 patients with paracoccidioidomycosis using four different techniques: (a) cell-block preparations stained with silver methenamine, (b) direct microbiologic examination, (c) smears stained with Shorr, and (d) smears stained with silver methenamine. Overall, cell-block preparations and smears stained with silver methenamine proved to be the most sensitive techniques, followed by smears stained with Shorr and direct microbiologic examination in decreasing order of sensitivity. Sputum cytology tended to be less positive in patients with interstitial pulmonary lesions as determined by chest X-ray than in patients with alveolar lesions. In addition to its high sensitivity, cell-block preparation technique allows storage of blocks and slides for further studies. PMID- 1886645 TI - Spatial interactions in color vision depend on distances between boundaries. PMID- 1886646 TI - Effects of ventricular colchicine injection on vasopressin-immunoreactive neurons and pyrogen-induced fever reaction in the guinea pig. PMID- 1886647 TI - [The intermediary nerve at its entry and exist site in the brain stem]. AB - On 119 brain stem halves the nerve root fasciculi of the intermediary nerve were examined in respect of their position relative to the facial and vestibulocochlear nerves. The following variants were seen: 1.) the intermediary nerve lies between the facial and vestibulocochlear nerves as stated in the textbooks, in 32.9% of the cases; 2.) in 18.5% of the cases it is entirely apposited to the vestibulocochlear nerve from the beginning and branches off from that nerve only later; 3.) part of the nerve root fasciculi are apposited to the vestibulocochlear nerve and the others originate between the facial and vestibulocochlear nerves. This was seen in 49.6% of the cases. PMID- 1886648 TI - [Value of MRT for therapy of para-sellar tumors]. AB - When planning treatment of tumours in the sella region it is of the utmost importance to obtain precise information about the localization, spread, and (if possible) the type of alteration. Aside from the classic radiographic methods of native diagnosis, angiography, and CT, MRI has been available for some years now. This is a method whereby images can be gained from the various stages of an energetic reaction in the biological substrate: tomograms are possible for any desired plane--those routinely needed for cerebral diagnosis from the horizontal, coronary, and sagittal planes and, given a further improvement of this technology, from special oblique planes which can be matched to the direction of a probable surgical approach. A number of examples demonstrate the significance of this new method, which is a valuable addition to the procedures used up to now: indeed, in some cases it is superior to them. It has been shown that most of the neighbouring structures which border on or have been pushed aside by the tumour in the sella region (blood vessels, brain, optic chiasma, subarachnoid spaces, and occasionally even bone structures) can be identified better than with the procedures used up to now. MRI has thus proved to be valuable, and occasionally indispensable, for the correct choice when considering the many therapeutic methods available for tumours in the sella region. PMID- 1886649 TI - Microsurgical management of suprasellar and intraventricular meningiomas. AB - A series of 78 intracranial meningiomas (68 suprasellar, 10 intraventricular) were operated on in our Institute after the advent of the operating microscope. In our review, we discuss the microsurgical technical problems related to the preservation of vascular and brain structures in the removal of intraventricular and parasellar meningiomas. Basic diagnostic criteria to plan correctly the surgical approach will be emphasized. Mortality and morbidity in parasellar meningiomas is, in our opinion, related to the experience of the surgeon in using the operating microscope rather then in using the laser and CUSA. We will also discuss the utility of preoperative embolization of the lesion as well as the indications for intraoperative EC/IC bypass. Finally, morbidity and mortality related to different approaches for intraventricular meningiomas will be discussed. PMID- 1886650 TI - Chiasmatic optic glioma. AB - Optic nerve glioma is a rare tumor usually occurring in small children. How these tumors should be treated, is a matter of controversy. Recommended treatment ranges from a wait-and-see policy to radical excision with or without subsequent radio- or chemotherapy. Comparative data on these lesion are limited, as there are no randomized investigations and long-term studies reported in the literature. In 11 patients interstitial radiotherapy was carried out, by the implantation of J-125 seeds following confirmation of the histological diagnosis. The results are compared with those of 10 patients who underwent only biopsy for histological confirmation. CT-stereotactic biopsy to verify the diagnosis with subsequent interstitial irradiation is presented as an alternative therapy for optic gliomas. PMID- 1886651 TI - Transsphenoidal removal of an intra- and suprasellar epidermoid cyst. AB - A case with an intra- and suprasellar epidermoid cyst removed by transsphenoidal route is presented. Problems in radiological and histologic differential diagnosis and advantages of transsphenoidal approach besides indications are discussed. PMID- 1886652 TI - Benign osteoblastoma of the sphenoid bone. AB - Benign osteoblastoma is a rare tumour of bone with a predilection for the spinal column and appendicular skeleton. The skull is an unusual site. We report a case in which the lesion affected the lesser wing of the sphenoid bone and extended from the middle cranial fossa to the orbital region. We discuss the distinguishing features of the tumour, reviewing the literature, and the treatment. PMID- 1886653 TI - Development of human neural transplantation. AB - The possibility of altering the course of Parkinson's disease by brain grafting is slowly becoming a reality through the efforts of many research groups worldwide. It has been shown that this procedure, as performed in high-level medical research centers, usually produces no permanent adverse effects and can effectively ameliorate parkinsonian signs in certain patients. This progress has served to reinforce our commitment to develop neural transplantation into an effective therapy to treat such a devastating neurodegenerative disease. We have summarized the most important events that have shaped the initial phase of this research. In the course of the last 4 years, considerable knowledge has been gained in the clinical neurosciences regarding the real potential of various brain grafting procedures in treating Parkinson's disease, their shortcomings, and their usefulness in carefully selected patients. There is still no consensus regarding the various fundamental aspects of human brain grafting in Parkinson's disease. Questions concerning surgical technique, candidate selection, the optimal brain regions for implantation, the optimal tissue for implantation, and the real usefulness of brain grafting must be addressed. The importance of the quality of adrenal medulla fragments for grafting, the requirement for immunosuppressors in fetal brain grafting, and the optimal fetal age and the amount of donor tissue for effective grafting are additional areas of concern. The potential of xenografting, preserved tissues, and genetically engineered cells for human brain grafting remain unanswered. The development of human neural transplantation is the responsibility and privilege of neurosurgery. PMID- 1886654 TI - Association of hypovolemia after subarachnoid hemorrhage with computed tomographic scan evidence of raised intracranial pressure. AB - Hypovolemic patients are more likely to suffer delayed cerebral ischemia and infarction after a subarachnoid hemorrhage (SAH). Prompt recognition and correction of hypovolemia may improve the outcome. We have identified computed tomographic (CT) scan findings that increase the probability of a patient presenting with hypovolemia soon after an SAH. The plasma volume (PV) of 25 patients admitted within 96 hours of an SAH was measured using radioiodinated serum albumin. The normal PVs were measured in an outpatient setting 6 months later or predicted from their total body water. Nine patients (36%) were found to be hypovolemic, defined as a fall in PV exceeding 10% of the normal PV (mean fall, 18 +/- 2%). Sixteen patients were normovolemic or hypervolemic (mean PV, +9 +/- 2%). The basal cisterns were compressed or obliterated on the CT scans of all hypovolemic patients compared with 12.5% of normovolemic patients (chi-square, 14.52; P less than 0.01). The probabilities of a patient being hypovolemic if the CT scan indicated raised intracranial pressure were high: hydrocephalus, P = 0.80; compression of the basal cisterns, P = 0.82; and compression of the basal cisterns associated with intracerebral hematoma or midline shift, P = 1.00. Patients with an SAH and radiological evidence of raised intracranial pressure should be considered at particular risk for systemic hypovolemia. PMID- 1886655 TI - The effect of nicardipine on vasospasm in rabbit basilar artery after subarachnoid hemorrhage. AB - This study was performed to examine the effect of the dihydropyridine calcium antagonist, nicardipine, on vasospasm after experimental subarachnoid hemorrhage (SAH) in the rabbit. The study was carried out in two parts: 1) effect of intravenous nicardipine (n = 45) and 2) effect of intracisternal nicardipine (n = 21). SAH was induced by injecting 5 ml of autologous arterial blood into the cisterna magna. In the intravenous study, there were five groups: 1) SAH without treatment; 2) SAH with vehicle (saline); 3) SAH and intravenous infusion of low dose nicardipine (0.01 mg/kg/h); 4) SAH and intravenous infusion of high-dose nicardipine (0.15 mg/kg/h); and 5) controls without SAH. The intravenous infusions were started immediately after SAH and continued for 48 hours until death. In the intracisternal study, there were three groups: 1) SAH without treatment; 2) SAH with intracisternal administration of nicardipine (0.37 mg/h); and 3) controls without SAH. Intracisternal infusions were begun 70 hours after SAH and continued for 2 hours until death. After perfusion-fixation, the basilar artery was removed and processed for morphometric analysis. In the intravenous study, vessels from animals subjected to SAH were significantly narrowed when compared with controls, although after high-dose nicardipine vessel caliber was slightly larger than in the other SAH groups. Animals given intracisternal nicardipine showed a nonsignificant reduction of caliber as compared with controls: only 12% decrease in diameter and 22% decrease in luminal area. In the rabbit SAH model, nicardipine had a very modest effect on vasospasm at the doses tested. PMID- 1886656 TI - Intracanalicular acoustic neurinomas. AB - The cases of 16 patients with acoustic neurinomas confined to the intracanalicular area are presented. These represent 2.7% of the 600 patients with acoustic neurinomas consecutively operated upon at the Neurosurgical Clinic at Nordstadt Hospital during the last 8 years. The comparatively earlier onset of vestibular symptoms and signs was characteristic of this group and precipitated diagnosis. The diagnostic reliability of magnetic resonance imaging was at least equivalent to that of air computed tomographic cisternography. Complete tumor removal was accomplished via the suboccipital approach in all patients, with 100% preservation of facial nerve and facial function; the cochlear nerve was preserved anatomically in 100% of the patients and functionally in 57%. No recurrence has occurred during follow-up periods of up to 8 years in all 16 patients. A broad spectrum of the current literature is considered, and purely intracanalicular acoustic neurinomas are discussed with regard to clinical characteristics, diagnostic steps-including neuroradiological and neurophysiological approaches-and surgical treatment and results. PMID- 1886657 TI - Long-term effects of radiotherapy and bromocriptine treatment in patients with previous surgery for macroprolactinomas. AB - The long-term effect of radiotherapy and bromocriptine treatment was retrospectively evaluated in 25 patients who had previously undergone transsphenoidal surgery for treatment of macroprolactinomas. Surgery had reduced the median serum prolactin (PRL) value from 613 micrograms/l, a reduction of 53%. Postoperative bromocriptine was administered to 21 of the 25 patients. In 14 of these patients, serum PRL values became normal or almost normal with medication. There were no radiological or ophthalmological signs of progressive tumor growth during bromocriptine treatment. Fourteen patients received postoperative radiotherapy. After withdrawal of bromocriptine in 13 of these patients an average of 7 years after radiotherapy, the median serum PRL value had further decreased by 95%. The PRL reduction was similar for all doses applied, 38 to 52 Gy. After withdrawal of bromocriptine in 8 patients not receiving radiotherapy an average of 7 years after operation, the median serum PRL level had further decreased by 75%. At follow-up, 18 additional instances of pituitary insufficiency had developed in the group receiving radiotherapy, compared with 8 cases of insufficiency in the group not receiving radiotherapy. Thus, because bromocriptine has a long-standing effect on prolactin secretion, and radiotherapy is associated with a notably high incidence of pituitary insufficiency, we propose that photon irradiation should be considered mainly for patients who are not candidates for surgical or medical treatment. PMID- 1886658 TI - Ependymoma: internal correlations among pathological signs: the anaplastic variant. AB - In a series of 298 cases of ependymoma, survival analysis identified some prognostic histological factors but failed to demonstrate a worse survival for the anaplastic variant diagnosed with the common criteria used for assessing anaplasia in primitive brain tumors. This finding suggests that either anaplastic ependymoma does not exist, or that the established criteria are not useful in its identification. To solve these problems, the association of histological, immunohistochemical, and ultrastructural signs in 173 intracranial cases was investigated and analyzed by means of contingency tables. Many signs had only focal distribution. Some signs, meaningful for anaplasia, such as very high cell density and number of mitoses, were found to be associated, whereas other signs usually considered indicative of anaplasia, such as endothelial hyperplasia, glomeruli, and necrosers, were not. In addition, pseudorosettes, mesodermic areas, and incomplete formation of perivascular pseudorosettes were signs associated with very high cell density and number of mitoses. Distribution of glial fibrillary acidic protein and vimentin, as well as other immunohistochemical and ultrastructural features, were not helpful, with the exception of microsettes found by electron microscopy. Our conclusion is that the anaplastic variant of ependymoma is recognizable only when some histological prognostic factors, such as cell density and number of mitoses, are maximally expressed. PMID- 1886659 TI - Anterior decompression in cervical spine trauma: does the timing of surgery affect the outcome? AB - To clarify the ideal timing of anterior decompression and stabilization for all patients with cervical spine trauma as well as its efficacy for patients with complete deficits, we reviewed the records of 103 consecutive patients with cervical spine trauma (50 incomplete deficits, Group A; 53 complete deficits, Group B) who underwent this procedure during a 5-year period at the Shock Trauma Center. We subdivided each group according to time of surgery: early and delayed (less than 24 and greater than 24 hours past injury, respectively). In Group A, 10 patients underwent early surgery and 40 patients underwent delayed surgery (range, 2 to 77 days past injury; mean, 13 days). One patient (2.5%) in the delayed group died. The following data refer to the early and delayed subgroups, respectively: average acute hospitalization, 20 and 22 days; patient motor score improvement (at discharge), 37.2 and 45.0%; functional grade improvement (at discharge), 5 (50.0%) and 9 (22.5%) patients. At 1-year follow-up, every patient who had had a deficit had progressed to a higher functional grade. In Group B, 35 patients underwent early surgery and 18 underwent delayed surgery (range, 2 to 45 days past injury; mean, 13 days). One patient (2.9%) in the early group died. The following data refer to the early and delayed subgroups, respectively: average acute hospitalization, 38.7 and 45.2 days (P less than 0.05); respiratory care (number of daily suction procedures), 6.0 and 9.86 (P less than 0.05); patient motor score improvement (at discharge), 3.9 and 4.5%; functional grade improvement (at discharge), 4 (11.4%) and 1 (5.6%) patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1886660 TI - Functional recovery after traumatic transtentorial herniation. AB - To elucidate the factors associated with functional recovery after traumatic transtentorial herniation, we reviewed the records of 153 consecutive patients admitted with clinical signs of transtentorial herniation (altered level of consciousness, anisocoria or pupillary unresponsiveness, and abnormal motor findings). Overall, 28 patients (18%) had a functional outcome: 14 patients (9%) made a good recovery and 14 were moderately disabled. Sixteen patients (10.5%) were severely disabled or vegetative, and 104 (60%) died. Compared with patients who died or were left severely disabled or vegetative, patients who had a good recovery were younger (21 versus 38 years), were significantly more likely to be children (less than or equal to 17 years old) and have anisocoria and a deteriorating Glasgow Coma Score (GCS), and were significantly less likely to be flaccid or have bilaterally fixed pupils; moderately disabled patients also had a lower median age and a higher frequency of anisocoria. There was no difference in the incidence of significant intracranial hematomas between patients with a functional outcome and those with a nonfunctional outcome. Twenty-seven percent of the 95 patients with anisocoria had a good outcome or moderate disability, whereas only 3.5% of the 58 patients with bilaterally fixed and dilated pupils at admission had a functional recovery (P less than 0.05). Age, level of consciousness, and the degree of residual upper brain stem function at admission appear to be the most important determinants of functional outcome after traumatic transtentorial herniation. PMID- 1886661 TI - Elevated cortical venous pressure in hydrocephalus. AB - To gain a better understanding of cerebrospinal fluid (CSF) hydrodynamics and their relationship to the cerebrovascular system, normal and naturally hydrocephalic dogs were studied to determine transmantle [lateral ventricle (LV) to subarachnoid space] and transparenchymal [LV to cortical vein (CV)] pressures. Pressure was also measured in the sagittal sinus, cisterna magna, and femoral artery. CV pressure has not previously been measured in hydrocephalus. Ventricular volume was determined by computed tomography. Four groups of animals were studied. In Group 1 (n = 5) transmantle pressure was measured; in Group 2 (n = 5), transparenchymal pressure in normal animals was measured. In Group 3 (n = 5) was measured all the pressures in spontaneously normal animals, and in Group 4 (n = 6) was measured the pressures in hydrocephalic animals. The pressure-volume index and CSF outflow resistance were also measured. LV volume in the normal dogs was 1.3 +/- 0.7 ml and in the hydrocephalic dogs was 5.1 +/- 2.7 ml (P less than 0.005). Although LV, subarachnoid space, and sagittal sinus pressures were elevated in the hydrocephalic dogs (15.1 versus 10.2, 16.4 versus 10.5, and 8.4 versus 5.2 mm Hg, respectively), the transmantle pressure and subarachnoid space to sagittal sinus gradients were not significantly altered. CV pressure was markedly elevated in the hydrocephalic animals (21.5 versus 11.7 mm Hg, P less than 0.005). The pressure-volume index and outflow resistance were not significantly different. These results suggest that an elevated CV pressure plays a role in the development and/or maintenance of hydrocephalus, and that the pathway for CSF absorption includes transcapillary or transvenular absorption of CSF from the interstitial space.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1886662 TI - Hemodynamic response with passive neck flexion in brain death. AB - Twelve brain-dead patients admitted to the Department of Traumatology, Osaka University Hospital, from July 1988 to August 1989 were studied. A hemodynamic response elicited by passive neck flexion was observed in 10 of the 12 patients. After passive neck flexion, blood pressure began to rise, and the heart rate increased slightly. Blood pressure peaked about 2 minutes after the initiation of neck flexion and then decreased gradually to the baseline level within a few minutes. These responses were suppressed completely by administration of the ganglion blocker trimethaphan camsilate, which suggests that the efferent pathway of the response is mediated by the sympathetic nervous system. PMID- 1886663 TI - The effect of apnea on brain compliance and intracranial pressure. AB - The effect of 2 minutes of apnea during endotracheal intubation on intracranial pressure (ICP), compliance, and cerebral blood volume (CBV) was studied in 19 adult dogs during normo-, hypo-, and hypercapnia. The compliance was measured from the cisterna magna in response to an intrathecal bolus injection (pressure volume index). CBV was monitored by radiolabeled red blood cell activity. These measurements were made before and after 2 minutes of apnea. At normocapnia (pCO2 of 35-40 mm Hg), a period of apnea resulted in an increase in ICP from 9.6 to 26.3 mm Hg, a decrease in compliance from 0.051 to 0.020 ml/mm Hg (60%), and an increase in CBV of 0.26 ml (9.6%). When the animals were hypocapnic (pCO2 of 24 28 mm Hg), ICP increased from 12.8 to 19.6 mm Hg, compliance fell from 0.041 to 0.029 ml/mm Hg(29%), and CBV increased 0.07 ml (3.1%). Hypercapnia (pCO2 of 50-58 mm Hg) before apnea resulted in an increase in ICP from 21.5 to 47.1 mm Hg, a decrease in compliance from 0.032 to 0.015 ml/mm Hg (52%), and an increase in CBV of 0.41 ml (13.4%). These results suggest that hyperventilation (hypocapnia) before intubation limits the adverse decrease in brain compliance and increase in ICP by reducing changes in cerebral blood volume. PMID- 1886664 TI - Evaluation and treatment of aneurysms of the vertebral artery: different strategies for different lesions. AB - Aneurysms of the vertebral artery and its branches are relatively uncommon lesions. Their anatomy and presentation can be quite variable. A spectrum of aneurysms of the vertebral artery is presented to illustrate the neuroradiological evaluation, surgical treatment, and perioperative management of these complex lesions. PMID- 1886665 TI - Ataxic hemiparesis associated with ipsilateral cerebellar syndrome caused by a paracentral gyrus lesion. AB - The authors report a case of ataxic hemiparesis and an ipsilateral cerebellar syndrome in relation to a glioblastoma of the paracentral gyrus region. The physiopathology of this clinical presentation caused by compression of the corticopontine tract is discussed. PMID- 1886666 TI - The danger of an ultra-early computed tomographic scan in a patient with an evolving acute epidural hematoma. AB - A case of an acute traumatic epidural hematoma that developed after an ultra early computed tomographic scan of the head is discussed. Serial neurological examinations in patients with head injuries are recommended. PMID- 1886667 TI - Reversal of a dense, persistent, holohemispheric neurological deficit after an endarterectomy of the carotid artery: case report. AB - The role and timing of a carotid endarterectomy in the setting of an acute ischemic stroke-in-evolution remain controversial. Although computed tomographic (CT) scans typically show no abnormalities in the acute stage, it is generally agreed that a dense neurological deficit (hemiplegia) and/or multiple modality neurological disturbance (involving motor, sensory, gaze, and visual field impairment) represent contraindications to surgical intervention. We present a case of an acute right holohemispheric neurological deficit including dense hemiplegia, hemisensory loss, gaze disturbance, hemineglect, and impaired level of consciousness. This persisted for 4 days while serial CT scans showed no evidence of infarction. Angiography revealed pre-occlusive stenosis of the right internal carotid artery with sluggish antegrade flow. The anterior collaterals of the circle of Willis were impaired, and the right middle cerebral artery territory filled via the posterior communicating artery. Despite the dense neurological deficit persisting for 4 days, a carotid endarterectomy was performed. Gradual neurological improvement was noted within hours of the operation, and all neurological deficits resolved within the subsequent 3 days. This case is consistent with prolonged holohemispheric hemodynamic compromise below the threshold of neurological dysfunction, but above the threshold of tissue infarction ("idling neurons"). Features assisting in the recognition of this unusual scenario and the indications and risks of revascularization in this setting are discussed. PMID- 1886668 TI - Hemorrhagic venous infarction after excision of an arteriovenous malformation: case report. AB - A case of arteriovenous malformation (AVM) in which postoperative hemorrhagic infarction developed, probably because of occlusion of the former draining veins, is reported. The hemorrhage developed in the temporal lobe 3 days after the initial operation and was located in the immediate vicinity of the site of the AVM. The following findings suggest that the postsurgical hemorrhage probably resulted from a venous thrombosis: 1) no evidence of residual AVM; 2) delayed onset of the hemorrhage, inconsistent with the time course of a hemorrhage developing according to the breakthrough theory or with insufficient hemostasis with a high-pressure afterload; 3) good correlation between the location of the hemorrhage and the occlusion of the draining veins; and 4) multifocal hemorrhage affecting both the gray matter and the subcortical white matter. Postoperative hemorrhagic infarction caused by thrombosis in the draining veins is rare, but it should be considered as a distinct postoperative complication after removal of an AVM. PMID- 1886669 TI - Neurogenic pulmonary edema: treatment with dobutamine. AB - In the case of a patient with complicating subarachnoid hemorrhage, an infusion of dobutamine was followed by a massive diuresis and regression of severe neurogenic pulmonary edema. It is suggested that the reduction in total peripheral vascular resistance and the increase in cardiac contractility accounts for the observed beneficial effect and indicate that dobutamine is a suitable drug for the treatment of neurogenic pulmonary edema. PMID- 1886670 TI - Sarcoidosis presenting as an isolated intramedullary tumor. AB - We report a case of isolated intramedullary sarcoidosis. The patient developed progressive signs that indicated a spinal tumor, which were investigated with contrast-enhanced magnetic resonance imaging scans. Magnetic resonance imaging clearly revealed an intramedullary lesion, but the diagnosis of sarcoidosis was made on the pathological analysis of the surgical specimen. Magnetic resonance imaging with contrast enhancement is reported in a histologically proven case of intramedullary sarcoidosis. Only 12 other cases of isolated intramedullary sarcoidosis have been reported. We review and discuss these cases according to their clinical presentation, the segmental location of the granulomas in the spinal cord, preoperative and operative diagnoses, and signs for systemic sarcoidosis. In none of the cases was the diagnosis of intramedullary sarcoidosis made before surgery. We think that surgical therapy for intramedullary lesions is the best way to diagnose rare instances of benign lesions like sarcoidosis and to treat them in an appropriate manner. PMID- 1886671 TI - Pachymeningitis associated with a pulmonary nodule. AB - The authors report a case of hypertrophic pachymeningitis, a rare cause of spinal cord compression. In this patient, dural inflammation was associated with a histologically identical pulmonary lesion. Such an association has not been described previously and supports the hypothesis that this disease is related to other connective tissue disorders. PMID- 1886672 TI - Inflammatory pseudotumor of the choroid plexus in Sjogren's disease. AB - We report an unusual case of inflammatory pseudotumor of the choroid plexus of the right lateral ventricle, manifesting as an intraventricular mass and causing unilateral hydrocephalus in a 48-year-old man who suffered from Sjogren's disease and subacute cutaneous lupus erythematosus. The lesion obliterated the normal choroidal architecture by a mixed chronic inflammatory process that was associated with reactive connective tissue changes. Immunohistochemical studies showed no light-chain restriction in the cells, and residual islands of transthyretin-positive epithelial cells were identified, implicating the choroid plexus origin of the mass. PMID- 1886673 TI - Dissecting aneurysm of the posterior cerebral artery: spontaneous resolution. AB - Dissecting aneurysms of the intracranial arteries display vascular pathological features that appear sporadically, generally affecting young adults. The clinical features of this condition may involve both ischemic episodes and hemorrhages. Posterior circulation is affected less than the rest of the intracranial arteries, and it is extremely rare to find the posterior cerebral arteries only affected. Mortality is high in patients where the lesion is located in the posterior intracranial circulation, although dissecting aneurysms limited to the posterior cerebral arteries may, to a certain extent, be benign. We report the case of a young woman with ischemia in the territory of the posterior cerebral artery that occurred subsequent to a dissecting aneurysm that resolved spontaneously to a complete remission, both clinically and as demonstrated by angiography. A review of the literature is made, analyzing the pathogenic, clinical, angiographic, and therapeutic characteristics of such lesions. PMID- 1886674 TI - Prominent meningeal "tail sign" in a patient with a metastatic tumor. AB - A prominent enhancement of the dura adjacent to meningiomas has been described as being pathognomonic of these tumors. We describe a case where a classic meningeal "tail sign" was associated with an extra-axial metastatic tumor attached to the tentorium. There was no tumor invasion of the dura. We conclude that this sign is nonspecific and can be seen with dural-based tumors other than meningiomas. PMID- 1886675 TI - Cystic cerebellar schwannoma: case report. AB - We report a case of cerebellar schwannoma in a 64-year-old woman. The tumor was defined on computed tomographic and magnetic resonance imaging scans and confirmed on surgery. The solid part of the tumor appeared to be derived from the inferior vermis of the cerebellum, the cystic part extending toward the medulla oblongata and the foramen magnum. The problem of preoperative diagnosis based on magnetic resonance imaging findings is discussed. PMID- 1886676 TI - Lumbar disc surgery: results of the Prospective Lumbar Discectomy Study of the Joint Section on Disorders of the Spine and Peripheral Nerves of the American Association of Neurological Surgeons and the Congress of Neurological Surgeons. AB - The Prospective Lumbar Discectomy Study enrolled 740 patients in a multiphysician, multicenter, consecutive patient protocol to evaluate the indications and efficacy of lumbar discectomy. Five hundred and thirteen patients could be evaluated at 3 months after surgery. Stepwise logistic regression showed that the factors of fraction of pain referred to the back, work-related injury, absence of back pain on straight leg-raise examination, correspondence of leg pain to typical radicular patterns, leg pain on straight leg-raise examination, and reflex asymmetry were independently predictive of good outcome from surgery. Univariate analysis of the case with different numbers of predictive factors present showed that use of the operating microscope, sensory deficit, central disc bulge, and free disc fragment were correlated with outcome only in subgroups. An analysis of unsatisfactory outcomes showed two patterns: one of failure as a result of mechanical back pain and one of failure as a result of radiculopathy. Factors predictive of outcome did not influence the type of failure. In a stepwise logistic regression analysis, facetectomy and preoperative sensory deficit were associated with increased likelihood of mechanical back pain failure, while preoperative motor deficit was associated with an increased likelihood of radicular failure. The results support several intuitively derived and commonly believed principles of lumbar disc surgery. PMID- 1886677 TI - Neurosurgery image manager. AB - Computer technology has become standard in many areas of medical practice, but computer-assisted instruction has not replaced standard textbooks and didactic lectures. This paper describes the development of a computer image-based educational system designed for neurosurgical instruction. The advantages and applications of this system for both clinical and academic use and the required software and hardware requirements are delineated. This computerized tutorial can organize and manipulate large amounts of data. The Neurosurgery Image Manager system contains an introductory help section, a self-assessment test in neurosurgery, and a data base of images from the video disc "The Slice of Life," produced at the University of Utah. Questions are taken from the Self-Assessment in Neurological Surgery series. Additionally, the system contains a reference index for all material in the tutorial, a scored clinical problems section, and a several hundred word glossary. The system is programmed using the Macintosh Hypercard authoring system. Large data bases can be manipulated and linked with graphics, text, and peripherals. Images are stored using the MacVision II digitizing system. The hardware necessary to operate the system and the method of implementation of Neurosurgery Image Manager are described. The prototype Neurosurgery Image Manager has been accepted by the Joint Committee on Education of the American Association of Neurological Surgeons and Congress of Neurological Surgeons as one of the computer formats for the next self-assessment tests. PMID- 1886678 TI - Transplantation of adrenal medulla and omentum to the putamen. PMID- 1886679 TI - Right temporal-lobe contribution to global visual processing. AB - The performance of 92 patients with unilateral temporal- or frontal-lobe excisions and 35 normal control subjects was tested under two experimental conditions (global, local) of a Stroop-type reaction-time task, employing either hierarchically structured letters or abstract designs as stimuli. In the local condition, subjects were asked to focus their attention on the small forms and to ignore the large form, whereas they were instructed to do the reverse in the global condition. The results showed that, in the local condition, the patients with right temporal-lobe lesions were less affected than the other groups by interference from the global aspect of the stimulus. This reduced sensitivity to the overall configuration of the stimulus was unrelated to the extent of hippocampal removal or to the presence of visual-field defects. These findings support the hypothesis that the human right temporal neocortex contributes to the global processing of visual information. PMID- 1886680 TI - Influence of different types of grasping on the transport component of prehension movements. AB - The main aim of the present study was to clarify whether different types of grasping may affect the transport component of prehension movements. To this purpose two experiments were carried out. In the first experiment the kinematics of arm movements (transport and manipulation components) were studied in eight normal subjects instructed to reach and grasp different objects located either 20 or 30 cm from their hand. The objects employed required two different types of grip: prehension with the whole hand and prehension with the index finger and the thumb (precision grip). In the second experiment subjects were instructed to point to the same objects employed in the first experiment. This experiment served as a control for the precision requirements related to the object size. The results showed that, once the precision requirements were taken into account, the transport component remained unmodified with the different types of grip. The time course of the manipulation component and its temporal relations with the transport component changed with the type of grasping. The maximal hand aperture was reached earlier in the precision grip than in the whole hand prehension and the temporal coupling with the transport component was weaker in the former condition than in the latter. The data are interpreted as further evidence in favour of independence between the transport and the manipulation "channels". PMID- 1886681 TI - Divided attention and metabolic brain dysfunction in mild dementia of the Alzheimer's type. AB - The relationship between reaction time (RT) measures under single-task and dual task conditions and resting levels of brain metabolism, as measured by positron emission tomography (PET), was examined in patients with mild dementia of the Alzheimer type (DAT) and age- and educationally-matched controls. Slowing of RT in dual-task but not single-task conditions correlated with reductions in brain metabolism in right premotor and right parietal association areas only for the mild DAT patients. The results suggest a relation between divided attention deficits and metabolic dysfunction of right frontal and parietal lobes in mild DAT patients. PMID- 1886682 TI - Contributions of stimulus encoding and memory search to right hemisphere superiority in face recognition: behavioural and electrophysiological evidence. AB - The relative contributions of stimulus encoding and memory search to right hemisphere (RH) superiority in face recognition were investigated in a memory search task with lateralized probe stimulus presentation. RH superiority in reaction time and latency of a late positive ERP component was independent of stimulus degradations, but increased as a function of memory set size. These results suggest equal efficiency of the hemispheres in stimulus encoding, but RH superiority in memory search. In addition, a long-lasting ERP negativity contralateral to the stimulated hemifield is discussed with reference to models of hemispheric processing in hemifield studies. PMID- 1886683 TI - The effects of word length and emotionality on hemispheric contribution to lexical decision. AB - The effects of emotionality and length on lateralized lexical decision of abstract nouns were investigated in 41 normal and three commissurotomized subjects. Emotionality had the same effect in both visual fields: Emotional words were responded to more accurately than neutral words. Length had different effects in the two visual fields: The accuracy of lexical decisions in the left visual field was selectively higher for four-letter words and in the right visual field it was selectively lower for six-letter words. The latency of lexical decisions revealed equivalent length effects in both visual fields. Of the commissurotomy patients, only L.B.'s left hemisphere performed above chance and revealed a length effect. Length effects are interpreted to reflect a change from a parallel graphic analysis to a sequential parsing strategy when resources are limited. Such a change can occur for words or nonwords in either visual hemifield. PMID- 1886684 TI - [The superior laryngeal nerve: an anatomical structure at risk during thyroid surgery]. AB - The effects of injury to the external branch of the superior laryngeal nerve (ESLN) during thyroid surgery are well known, while the frequency and consequences of ESLN lesions aren't today well known. The Authors report their own experience of the incidence of ESLN injuries in thyroid surgery. PMID- 1886685 TI - [Spigelian hernia: our experience during a decade]. AB - The Authors report a small series (three cases) of Spigelian hernias and underline the rarity of this pathology (0.2% in their series of hernias of the abdominal wall). They determine the anatomical features of the region, recall clinical features and discuss the most interesting points differential diagnosis and therapy. PMID- 1886686 TI - [Appendectomy without inversion of the stump. A valid alternative. Our experience in 690 cases]. AB - The paper reports the Authors' ten year experience on simple ligation in appendicectomy. After having reviewed the various surgical procedures, the Authors report their clinical experience and, considering the good postoperative results with this method, regard this procedure as an alternative to the technique of ligation with inversion of the stump in appendicectomy. PMID- 1886687 TI - [Primary and secondary hyperparathyroidism. Analysis of our results]. AB - The Authors introduce their experience of primary and secondary surgical treatment of hyperparathyroidism, pointing out at first the good confidence of echography, scintigraphy and TAC, in the pre-operating diagnostic of the parathyroid glands localization and then the satisfactory clinical results with a follow-up which, up to date, has not shown any relapse. PMID- 1886688 TI - [Endoscopic sclerotherapy of esophageal varices]. AB - Magnetic tape recordings of endoscopic images relating to pathologies with it is extremely important to follow morphological changes after treatment offer unquestionable advantages especially in the field of sclerosing endoscopic therapy for esophageal varices. This study--which was carried out using a 3/4 inch U-Matic videotape lasting 10 minutes--confirm the above statement. The criteria of selection for sclerosing techniques are illustrated according to the authors' personal evaluations made on the basis of experience accumulated during more than 10 years' activity; the results of modulated treatment are compared as both emergency and elective treatment, used as the single therapy or following deconnection or portosystemic derivation operations. The choices are confirmed by the number of successful outcomes, with only minimal and almost always easily controlled complications. This has led to the method's inclusion in clinical practice as yet another means of controlling hemorrhages due to portal hypertension, in addition to permitting a marked increase in the percentage of success following deconnecting and derivative operations performed in patients in better conditions of clinical compensation. PMID- 1886689 TI - [Treatment of perforation of the cervical esophagus during diagnostic endoscopy]. AB - Early diagnosis of esophageal perforation is critical. We believe that the treatment of each case must be individualized. The management of perforation in our series has been "conservative" in two cases, for small perforations; and "operative", suture closure and drainage, in the remainder, for a large perforation with contamination of the mediastinum. PMID- 1886690 TI - [Carcinoid of the appendix. Presentation of a case]. AB - The paper describes a recent case of carcinoid of the appendix in a 15 year old patient, operated for appendicitis. The diagnosis was found incidentally by histologic examination. Following a review of the literature the Authors discuss the epidemiology and clinical aspects of the appendiceal carcinoid, the most common tumour of the appendix. PMID- 1886691 TI - [Perianal Verneuil's disease]. AB - One case of perianal hidradenitis suppurativa is reported. The Authors discuss the clinical, diagnostic and histopathological features and emphasize the primary importance of correct diagnosis among perianal suppurative diseases. PMID- 1886692 TI - [Acute cecal diverticulitis. Presentation of 2 cases]. AB - Two cases of acute caecal diverticulitis are reported. The Authors describe the clinical aspects, diagnostic procedures, histological pictures and surgical treatment. Particular emphasis is also placed on problem of a correct preoperative diagnosis. PMID- 1886693 TI - [A case of teratoma of the urachus]. AB - The paper reports a case of teratoma of the urachus in a 53-year-old patient. The difficulties of diagnosing this pathology are underlined, in particular in relation to the rarity of the site of which no other examples have been reported in the literature. PMID- 1886694 TI - [Retroperitoneal tumors. Description of a clinical case]. AB - The paper reports a case of retroperitoneal leiomyosarcoma; it appeared following the onset of left lumbocruralgia pain which was recacitrant to medical and physical therapy and was followed by loss of weight and endoabdominal swelling. The paper also discusses retroperitoneal tumors, paying particular attention to their diagnosis and surgical treatment. PMID- 1886695 TI - [Lymphoid sarcoidosis with axillary localization. A clinical case]. AB - Following the case of a patient affected by bilateral axillary sarcoidosis of the lymph nodes the Authors of this paper have carried out a study with particular attention to the histological diagnosis, and making use of both optic and electron microscopy. The case here presented did not have the typical pattern of sarcoidosis. We underline that it was sarcoidosis of the lymph nodes in a patient with no evidence of lung alteration (Chest X-Rays were negative). It is rare case on the basis of world surveys. PMID- 1886696 TI - Suicide liability. PMID- 1886697 TI - HMOs today. PMID- 1886698 TI - 1991 inaugural address: Keep on hoein'. PMID- 1886699 TI - Year 2000: better health for New Jersey. PMID- 1886700 TI - Nuclear medicine and pediatric nephrology. AB - Radionuclide cystography and renal scintigraphy are the diagnostic procedures of choice in conjunction with ultrasonography in the workup of pediatric urologic or nephrologic patients. Two interesting case reports--a six-month old and a three month old--are presented. PMID- 1886701 TI - High posterior approach to the internal jugular vein. AB - Thirty-seven patients underwent the high posterior approach to the internal jugular vein with a 97.3 percent success rate. The authors present a simple technique for central venous cannulation. A comparison is made to three standard methods of jugular vein catheterization. PMID- 1886703 TI - MSNJ Golden Merit Award recipients. PMID- 1886702 TI - Part I: Basic approach to health screening. AB - A variety of recommendations exists regarding the screening of disease in asymptomatic individuals. In the first of a two-part series, the authors provide a basic approach to health screening, including historical background, barriers, and criteria. PMID- 1886704 TI - Group B streptococcus: the effectiveness of screening and chemoprophylaxis. AB - Although antepartum screening for Group B Streptococcus is not ideal, it may be the most practical approach until rapid tests are proven to be useful in this clinical setting. The efficacy has been established for intrapartum chemoprophylaxis with a penicillin antibiotic of patients with a positive antepartum culture. There is evidence that supports the concept for selective intrapartum chemoprophylaxis in some populations. Intrapartum chemoprophylaxis prevents maternal morbidity. Rapid tests for intrapartum diagnosis of Group B streptococcus colonization appear promising, providing results are available in time for therapy to be administered before delivery. PMID- 1886705 TI - Advanced abdominal pregnancy. PMID- 1886706 TI - The 5' non-coding region of the BCR/ABL oncogene augments its ability to stimulate the growth of immature lymphoid cells. AB - The Philadelphia chromosome (Ph1, t9:22;34:q11) is a reciprocal translocation between chromosome 22 and chromosome 9 which results in the formation of the chimeric BCR/ABL oncogene. Alternative forms of BCR/ABL are produced by splicing different sets of exons of the BCR gene to a common set of c-ABL sequences. This results in the formation of an 8.7 kilobase mRNA that encodes the P210 BCR/ABL gene product or a 7.0 kilobase mRNA that encodes the P185 BCR/ABL gene product. Both BCR/ABL transcripts derive their 5' non-coding sequences from the BCR gene locus. This 5' region is over 500 nucleotides in length, has a GC content greater than 75% and has a short open reading frame. To determine if this unusual 5' non coding region plays a role in BCR/ABL transformation, we prepared retroviral vectors containing identical BCR/ABL coding regions but differing in the length of the BCR 5' non-coding region. Matched viral stocks were evaluated for their ability to transform bone marrow in vitro and for their ability to cause tumors when inoculated into 3- to 4-week-old mice. In this report we present the unexpected finding that the BCR/ABL 5' non-coding region augments the transforming activity of both P210 and P185 BCR/ABL in vitro. In vivo, BCR/ABL is a weak tumorigenic agent and its potency is enhanced by the presence of the 5' non-coding region. PMID- 1886707 TI - An alternatively spliced c-mil/raf mRNA is predominantly expressed in chicken muscular tissues and conserved among vertebrate species. AB - The chicken c-mil gene produces two mRNA species generated by an alternative splicing mechanism. These two transcripts differ at least by the presence or absence of a 60 nucleotide exon (E7a) localized at the splice junction of c-mil exons 7 and 8. By using RNAase protection assays, we have analysed the pattern of expression of these two mRNA species in several chicken tissues. Here we report that the two c-mil mRNAs are differentially expressed in chicken tissues: the mRNA lacking E7a is detected in all tissues tested, while the mRNA containing E7a is detected only in the skeletal muscle, heart and brain. Sequences homologous to E7a have also been detected in DNAs from quail, mouse and human cells and their sequencing revealed that the alternative E7a is structurally preserved in these species. By PCR analyses performed on RNAs extracted from muscular tissues of these species, we also show that the alternative splicing mechanism described in chicken also occurs in these species. PMID- 1886708 TI - Detection of p53 gene mutations in human brain tumors by single-strand conformation polymorphism analysis of polymerase chain reaction products. AB - Single-strand conformation polymorphism analysis of polymerase chain reaction products (PCR-SSCP analysis) was used for detection of mutations of the p53 gene in surgical specimens of human brain tumors. Six of 45 brain tumors showed mobility shifts in the analyses. These six tumors also showed loss of a normal allele. The samples were examined further by direct sequencing. Results showed that four of them had single-base substitutions and the other two had deletions of one and eight base pairs. Five of the six mutations detected were clustered in highly conserved regions of the p53 gene. The frequency of p53 gene mutations in primary brain tumors examined was 9.8%. We also found two new polymorphic markers in the p53 gene, one in intron 7 and the other in an Alu repeat in exon 11. Both markers could be detected by SSCP analysis. Using these two markers, we found two cases of loss of heterozygosity in other brain tumor specimens. Results suggested that aberrations of the p53 gene were not correlated with the malignancy of some types of brain tumors such as anaplastic astrocytoma and glioblastoma, contrary to previous observations on colorectal cancers. PMID- 1886709 TI - Loss of myb expression in an aggressive SJL/J B-cell lymphoma. AB - SJL mice spontaneously develop B-cell lymphomas that can be propagated by transplantation into syngeneic mice. These tumors usually have an indolent phenotype and require at least several weeks to produce morbidity following transplantation. However an aggressive lymphoma (RCS5) has been found that produces morbidity within days of transplantation. RCS5 cells fail to express the H-2Ds class I major histocompatibility complex antigen, whereas indolent tumors express H-2Ds. To identify genetic factors that may contribute to the tumorigenicity of B-cell lymphomas in SJL mice, tumor genomes were analyzed for mutations in cellular oncogenes. No rearrangements were detected by Southern hybridization analysis in tumors at the abl, myc, mbcl-2, Ha-ras, Ki-ras and raf loci. Indolent tumors were not rearranged at the myb oncogene, however alterations were detected in both myb alleles in RCS5. Northern hybridization analysis on RNA from in vivo-derived tumor preparations failed to detect any myb transcripts in RCS5. The loss of normal myb expression could directly contribute to the aggressive phenotype of RCS5. Alternatively, expression of the RCS5 myb allele may have contributed to early stages of tumor development. The possibilities that the observed myb mutations affect tumor aggressiveness and H 2Ds expression are discussed. PMID- 1886710 TI - Heterogeneous expression of the product of the retinoblastoma susceptibility gene in primary human leukemia cells. AB - To investigate the possible role of the product of the retinoblastoma susceptibility gene, pRB, in leukemogenesis, we examined fresh leukemia cells from 56 cases of primary leukemia (AML, 32; ALL, 12; CML-BC, 9; CLL, 3) for expression of pRB by using an immunoblotting assay with anti-pRB monoclonal antibodies PMG 3-245 or 3-340. Expression of the 70 kDa heat shock protein (Hsp70) was examined simultaneously as an internal control. pRB was found to be absent or expressed at an abnormally low level in 13 of 56 cases. Abnormal expression of pRB was most common in AML (8/32) and CML-BC (4/9), and less common in ALL (1/12). Expression of pRB was not induced in two cases of pRB- AML cultured for 24 h with GM-CSF, indicating that pRB expression could not be induced by increasing the rate of proliferation. The eight cases of AML lacking pRB protein were examined for RB1 mRNA by Northern blot. Two lacked RB1 mRNA and six had a normal-sized mRNA (approximately 4.7 kb), although the amount of RB mRNA was very low in some cases. RB1 gene structure was normal by Southern blot in all eight cases lacking pRB protein which were studied. These results show that lack of pRB expression is relatively common in human myeloid leukemias, and suggests that loss of pRB expression could contribute to the altered growth control of these cells. PMID- 1886711 TI - The MEL gene: a new member of the RAB/YPT class of RAS-related genes. AB - The MEL gene was identified following transfection of NIH3T3 mouse fibroblasts with DNA from a human melanoma cell line. The human MEL gene has been localized to 19cen-p13.2, a region in which translocation breakpoints occur in a number of malignancies. We have identified and sequenced human and mouse MEL cDNA clones which show homology of 92% and 96% at the nucleotide and amino acid levels respectively. The predicted human MEL protein shows only six amino acid differences between it and the recently described dog RAB8 protein. All of these changes occur in the 30 amino acids at the C-terminal of these proteins. MEL is similar to the RAB/YPT proteins in the region corresponding to the putative effector domain, suggesting that they may interact with the same cellular substrates. However, MEL contains a C-terminal CAAX motif in common with the majority of the RAS superfamily, unlike YPT1 and the majority of the RAB proteins. PMID- 1886712 TI - Endogenous HeLa p53 proteins are easily detected in HeLa cells transfected with mouse deletion mutant p53 gene. AB - It has been reported [Matlashewski et al. (1986). Eur. J. Biochem., 154, 665-672] that HeLa cells contain no detectable p53 protein, although they contain p53 mRNA which is translationally active. Here it is shown that endogenous HeLa p53 proteins were easily detected in HeLa cells transiently expressing mouse deletion mutant p53 gene after transfection with the appropriate recombinant plasmid. This detection was obtained by immunoprecipitation coupled with SDS-PAGE as well as by Western blotting experiments. Our results strongly suggest that HeLa p53 mRNA is actually translated in vivo, generating an extremely unstable p53 protein. Considering that the HeLa cell line is a HPV-18-positive human cervical carcinoma cell line, this high instability of HeLa p53 proteins is in keeping with the finding that E6 oncoprotein encoded by human papillomavirus 16 or 18 promotes the degradation of p53 proteins [Scheffner et al. (1990). Cell, 63, 1129-1136]. PMID- 1886713 TI - Proto-oncogene expression in avian hematopoietic tissues. AB - Previous findings from this laboratory (Kim & Baluda, 1988) have shown that the proto-oncogenes ETS, FPS, MHT (RAF), MYC and REL are expressed in avian myeloblastosis virus (AMV)-transformed cells, whereas the MYB gene is repressed. In this study five different chicken hematopoietic tissues which contained varying concentrations of target cells for AMV transformation were analyzed to determine whether the expression of these proto-oncogenes resulted from, or was altered by, v-myb-induced leukemogenesis. Poly-A+ RNA from hematopoietic cells of 11-13 day yolk sac, 16 day embryonic spleen, 1 day post-hatch bursa of Fabricius, bone marrow and thymus, as well as from chicken embryonic fibroblasts (CEF) was examined by Northern blot analysis. All five proto-oncogenes were found to be expressed in the normal hematopoietic tissues. The ETS, MHT (RAF), MYC, and REL genes, but not FPS, were expressed in CEF. The expression of these five proto oncogenes was not quantitatively or qualitatively altered in AMV-transformed myeloid cells as compared with their normal counterparts. While their expression is part of the hematopoietic phenotype of the target cells and as such is necessary for susceptibility to AMV transformation, it is not sufficient because thymocytes with a high level of expression are not transformed. This is in contrast to MYB expression, which is totally repressed in leukemic cells but probably not as a result of v-myb expression. PMID- 1886714 TI - Putative structure of the FGF6 gene product and role of the signal peptide. AB - The human FGF6 gene is an oncogene related by sequence similarities to the fibroblast growth factor (FGF) gene family, which encodes mitogenic peptides implicated in various physiological processes including angiogenesis, morphogenesis, tissue regeneration and survival and oncogenesis. Nucleotide sequence analysis of the FGF6 gene and of cDNA clones revealed an open reading frame able to code for a protein of 208 residues. The FGF6 protein shares 32-70% residues with the other members of the family within the C-terminal two-thirds of the molecule. In vitro, three in-frame ATG codons are able to initiate the translation of three peptides of 175, 198 and 208 residues. These three peptides differ at their amino termini with respect to the relative position of a hydrophobic leader peptide, which extends from residues 16 to 40, and is therefore absent from the shorter (175 amino acids) form. In-vitro analysis indicates that this signal peptide is able to drive the FGF6 protein through the endoplasmic reticulum, where it becomes glycosylated. The presence of this signal peptide sequence appears essential for the in vivo transforming capacity of the FGF6 gene. PMID- 1886715 TI - Stimulation of methotrexate resistance and dihydrofolate reductase gene amplification by c-myc. AB - We have hypothesized that the c-myc oncogene might promote DNA amplification. Resistance to methotrexate (MTX), a widely used cancer chemotherapeutic agent, often results from amplification of the gene coding for the target enzyme, dihydrofolate reductase (DHFR). We report here that gratuitously induced expression of c-myc in rat fibroblasts grown in the presence of MTX greatly increases the number of colonies resistant to the drug. This effect is not related to an alteration of cell growth, and it can also be observed to a lesser extent when c-myc is induced prior to selection in MTX. The DHFR gene is amplified in nearly half of the colonies cultured under selection conditions. Given the likely role of the c-myc product in DNA replication, these results strongly suggest that expression of c-myc plays a role in methotrexate resistance by promoting DNA amplification. PMID- 1886716 TI - Normal c-abl gene protein--a nuclear component. AB - The subcellular distribution of the c-abl and bcr-abl gene products from KG1A and K562 cells has been studied by two different techniques. Firstly, physical disruption followed by subcellular fractionation was used to demonstrate that normal c-abl (p145) was recovered from the cytosol and the nuclear fractions of KG1A cells. In contrast, bcr-abl products were recovered exclusively from the cytosol fraction of K562 cells. Secondly, indirect immunofluorescence was used to localize c-abl protein to the cytoplasm, nuclear membrane and infrequently to the nucleus of KG1A cells and bcr-abl protein to only the cytoplasm of K562 cells. Thus both the approaches indicate that there is a component of normal c-abl products which appears to be nuclear and this is not reflected in the distribution of the bcr-abl 210 kDa protein, which remains cytosolic. PMID- 1886717 TI - Loss of growth control by TGF-beta occurs at a late stage of mouse skin carcinogenesis and is independent of ras gene activation. AB - The relationship between the expression of a mutant ras gene in epithelial cells and loss of responsiveness to the negative effects of transforming growth factor beta (TGF-beta) is presently unclear. We have investigated this question using a series of cell lines derived from benign and malignant mouse skin tumours which express mutant forms of the H-ras gene. Immortalised, non-tumorigenic mouse epidermal cells respond to TGF-beta by cessation of growth, whereas in a series of malignant carcinoma lines the response was substantially reduced. Introduction of a mutant H-ras gene into the immortalised cells did not lead to any appreciable change in TGF-beta responsiveness, suggesting that initiation of carcinogenesis by ras mutation does not directly alter growth control by this pathway. Of two non-tumorigenic papilloma lines tested which had mutant H-ras genes, one retained complete sensitivity to TGF-beta, whereas the other showed a similar response to carcinomas. We conclude that growth control by TGF-beta is lost at a relatively late stage of carcinogenesis in this system, and is independent of ras gene activation. PMID- 1886718 TI - Differential sensitivity of human colonic adenoma and carcinoma cells to transforming growth factor beta (TGF-beta): conversion of an adenoma cell line to a tumorigenic phenotype is accompanied by a reduced response to the inhibitory effects of TGF-beta. AB - The growth of three non-tumorigenic human colonic adenoma cell lines, designated AA/C1, RG/C2 and RR/C1, was inhibited by low concentrations of transforming growth factor beta (TGF-beta) (0.05-0.5 ng ml-1). However, the growth of five human colon cancer cell lines under identical conditions was resistant to high concentrations of TGF-beta (2-10 ng ml-1). This is the first report of well characterized premalignant human colonic cells showing sensitivity to TGF-beta. The TGF-beta-sensitive adenoma cell line AA/C1 was derived from a relatively large adenoma with a K-ras gene mutation and represents a relatively late-stage adenoma, indicating that loss of response to TGF-beta occurs at a relatively late stage in colorectal carcinogenesis and that the presence of a ras gene mutation does not necessarily confer resistance to TGF-beta. Of further interest, the RG/CZ cell line has a p53 mutation showing that p53 mutations do not necessarily lead to TGF-B insensitivity. Furthermore, in this paper we show that the conversion of the AA/C1 adenoma cell line to a tumorigenic phenotype [Williams et al., (1990) Cancer Res., 50, 4724] is accompanied by a reduced response to the growth-inhibitory effects of TGF-beta up to 10 ng ml-1. Reduced responsiveness to the inhibitory effects of TGF-beta may be an important event in the loss of growth control in colorectal carcinogenesis. PMID- 1886720 TI - Nursing's agenda promotes access to health care for all. PMID- 1886721 TI - PNA survey examines recruitment of minority students into nursing. PMID- 1886719 TI - Two site-specific deletions and t(1;14) translocation restricted to human T-cell acute leukemias disrupt the 5' part of the tal-1 gene. AB - Analysis of several cases of t(1:14)(p32;q11) translocation present in 3% of T cell acute leukemias (T-ALL) has revealed the tal-1 gene. This gene encodes a helix-loop-helix protein. It has been found to be expressed in normal bone marrow and in leukemic T-cell and erythroleukemia cell lines, but not in normal T cells. Recently, a site-specific deletion, tald, renamed tald1 in this paper, has been detected in a high proportion of pediatric T-ALL, which arose by a site-specific DNA recombination between tal-1 and a new locus termed SIL. In this study we searched for structural rearrangements within tal-1 in a panel of 134 non selected leukemic patients (including 66 with T-ALL). Only 6% of patients with T ALL harbored the tald1 deletion. A second specific deletion termed tald2 was observed in another 6% of T-ALL patients; it involves another site within tal-1 plus the same site as tald1 in the SIL locus. Similarly to tald1 deletion, tald2 junctions harbor structural characteristics that are reminiscent of aberrant recombinase activity. Moreover, we report a detailed analysis of the tal-1 gene structure. Transcription analysis and in vitro translation data are consistent with the differential expression of several TAL-1 protein species containing the HLH motif but differing in their amino terminus. Taken together, our data indicate that t(1;14) translocations and both tald deletions disrupt the 5' part of the tal-1 gene, placing its entire coding sequences under the control of the regulatory elements of the TCR-delta gene or the SIL gene, both of which are normally expressed in T-cell lineage. PMID- 1886722 TI - Schools of excellence: an investment in the future. PMID- 1886723 TI - Inadequate staffing threatens patient care. PMID- 1886725 TI - Nurses lack health insurance. PMID- 1886724 TI - Win/win! Where do we as nurses begin? PMID- 1886726 TI - Fair share and economic general welfare. Interview by Robert Campbell. PMID- 1886727 TI - Factors influencing the regeneration of axons in the central nervous system. AB - Damage to the central nervous system (CNS) causes damage to neurons. This damage can result in the complete death of neurons, or in them becoming disconnected from their inputs or target structures due to disruption of axons. The main reason why damage to the human CNS is so disastrous and disabling is that axons will not in general regenerate in the mammalian brain, and neurons once lost are not replaced. In order, therefore, to repair the CNS, techniques will have to be developed to replace dead neurons, and induce axon regrowth. Central to the technologies necessary for brain repair is the ability to induce and control the growth of axons, since in a damaged brain both surviving and newly implanted neurons must grow axons to make or remake appropriate synaptic connections. Worthwhile treatments, however, do not necessarily require the repair of all the damaged circuits in the CNS, it may be possible to substantially improve the function of patients with relatively few reconnected axons, if those axons are ones which mediate particularly important behaviours, such as respiration, bladder control, or hand and arm movements. PMID- 1886728 TI - Regeneration of lesioned CNS axons by neutralisation of neurite growth inhibitors: a short review. PMID- 1886729 TI - Transplants of fetal neural tissue and autologous peripheral nerves in an attempt to repair spinal cord injuries in the adult rat. An overall view. AB - Embryonic neurons and autologous peripheral nerve segments constitute selected materials for studying central nervous system plasticity and repair in adult mammals. Transplanted to the brain or the spinal cord, the former are possible substitutes designed to replace lost or deficient host neurons while the latter have useful stimulating and guiding effects upon axonal regrowth from surviving axotomized neurons. Consequently, these techniques give rise to interesting prospects for short and medium range fundamental research as well as for possible medium and long-term clinical applications. From a basic viewpoint, utilisation of such transplants is designed to study the survival, the morphological and biochemical differentiation, the reafferentation, the expression of potentialities for plasticity, axonal growth or regeneration, synaptogenesis, of host as well as of transplanted embryonic neurons. From a clinical viewpoint these studies should attempt at finding solutions to counteract the effects of severe traumatic or neurodegenerative lesions of the brain and of the spinal cord which until now appear quite refractory to therapeutic approaches. PMID- 1886730 TI - Upward displacement of the centre of gravity in paraplegic patients. AB - The centres of gravity of 44 complete chronic spinal cord injured patients and 24 normal subjects were measured using a gamma ray scanner (Barycentremetre). The results are expressed as a percentage of body length and as anatomical level. The mean weight of paraplegic patients was 12kg less than the controls. The centre of gravity was 5% of body length higher in the paraplegic patients than in the controls, equivalent to 3 to 4 vertebrae level. The importance of such changes in the centre of gravity for the design of stable wheelchairs is discussed. PMID- 1886731 TI - Social role functioning following spinal cord injury. AB - The Katz Adjustment Scale--Relatives Form was completed by the wives of 27 hospital-discharged spinal cord injured (SCI) patients. Their ratings of the spouses' social adjustment and behaviour were compared to available community and psychiatric norms. Overall, spouses rated their SCI husbands as performing significantly more socially inappropriate behaviours compared to ratings of 'normals' but as engaging in significantly less socially inappropriate behaviours compared to the ratings of psychiatric patients. SCI patients were perceived as performing the same levels of social activities as 'normals', but engaging in less free-time activities compared to both 'normals' and psychiatric patients. These results mirror similar analyses comparing moderate and severe head injury victims with normal and psychiatric norms. The implications for rehabilitation and counselling of families of traumatically disabled patients are discussed. PMID- 1886732 TI - N-acetyl-beta-D-glucosaminidase in the localisation of urinary tract infection in patients with spinal cord injury. AB - This study evaluates the pattern of urinary N-acetyl-beta-D-glucosaminidase (NAG) isoenzyme excretion in patients with spinal cord injury (SCI) and its use as a diagnostic tool in localising the site of urinary tract infection (UTI). NAG-B excretion in 27 control SCI patients (mean 207.78 units) was significantly higher than in 10 normal controls (mean 12.6 units) p less than 0.001). The relative isoenzyme distribution as represented by NAG-B/Total NAG percentage is however similar in both groups, 24.27 and 20.38% respectively. NAG-B excretion in 6 SCI patients with upper UTI was not significantly higher than in 12 SCI patients with lower UTI. NAG-B/Total NAG percentage was significantly different between these two groups (35.3% and 24.98% respectively, p less than 0.05). There was no significant difference in NAG-B excretion or NAG-B/Total NAG percentage between control SCI patients and those with lower UTI. The results indicate that there is a non-selective increase in urinary NAG excretion in control SCI patients and those with lower UTI. In SCI patients with upper urinary UTI there is a selective increase in NAG-B excretion. The overlap in enzyme values between the different groups suggests that the test may not be clinically useful in localising the site of UTI. PMID- 1886733 TI - Effect of continuous versus intermittent turning on nursing and non-nursing care time for acute spinal cord injuries. AB - The present study was conducted to determine whether automated, continuous turning beds would reduce the nursing care time for spinal cord injured (SCI) patients by freeing hospital staff from manual turning of patients every 2 hours. Seventeen patients were randomly assigned to continuous or intermittent turning and were observed during the 8 hour shift for 1 to 18 days following injury. Trained observers recorded the time taken for patient contact activities performed by the nursing staff (direct nursing care) and other hospital staff. The mean direct nursing care time per dayshift per patient was 130 +/- 22 (mean +/- SD) minutes for 9 patients managed with continuous turning and 115 +/- 41 (mean +/- SD) minutes for 8 patients managed with intermittent turning. The observed difference in care time between the two treatment groups was not significant (p greater than 0.05). Numerous factors including neurological level, time following injury, and medical complications appeared to affect the direct nursing care time. Although continuous turning did not reduce nursing care time it offered major advantages for the treatment of selected cases of acute SCI. Some major advantages of continuous turning treatment were observed. Spinal alignment was easier to maintain during continuous turning in patients with injuries of the cervical spine. Continuous turning allowed radiological procedures on the spine, chest and abdomen to be more easily performed without having to alter the patients' position in bed. Therapy and nursing staff indicated that the continuous turning bed facilitated patient positioning for such activities as chest physiotherapy. With continuous turning, one nurse was sufficient to provide care for an individual SCI patient without having to rely on the assistance of other nurses on the ward for patient turning every 2 hours. PMID- 1886734 TI - Spinal injury rehabilitation: do staff and patients agree on what they are talking about? AB - The psychological effects of spinal cord injury on patients themselves have been discussed in a number of articles, but few studies have been made of patients and staff, perceptions of the effectiveness of the treatment they receive and supply. An earlier investigation by the present authors showed that there were differences between the views of staff and of patients in terms of their understanding of rehabilitation. As a consequence, a number of procedural changes were implemented in the Spinal Unit, in an attempt to improve the information provided for patients and their relatives, and the selection and support of staff. Reanalysis of the staff and patients views of rehabilitation were carried out 12 months later using a standardised questionnaire and any changes in response were noted. The present findings are analysed, and the potential implications for other units are noted. PMID- 1886735 TI - Quadriparesis in the Laurence-Moon-Biedl-Bardet syndrome: case report. AB - A 36 year old patient known to suffer from the Laurence-Moon-Biedl-Bardet syndrome (LMBBS) developed spastic quadriparesis. The typical features of the syndrome, presented by this patient were polydactyly, obesity, hypogonadism, retinitis pigmentosa and relative mental retardation. Severe spinal cervical and lumbar canal stenosis imaged by plain X-rays and computerised tomography was found. Magnetic resonance imaging showed significant atrophy of the spinal cord, indicating that the cause of the quadriparesis was cervical myelopathy. The patient underwent laminoplasty with some improvement. PMID- 1886736 TI - The role of the pediatrician in oral health care. AB - Many of the dental problems of childhood can be prevented if the physician recognizes and encourages good preventive habits, treats when indicated, and refers appropriately. With sound knowledge of health and disease of the oral and dental structures, the physician can enhance the chances of children growing up under optimal medical and dental conditions. PMID- 1886737 TI - Craniofacial growth from infancy through adulthood. Background and clinical implications. AB - The purpose of this article was to enable the pediatrician to identify and understand the implications of common facial growth problems in children and adolescents. Problems with facial growth can result in aesthetic and functional complaints. Using a simple method of clinical evaluation, the pediatrician can identify facial growth problems in the anteroposterior, vertical, and transverse dimensions. These problems can then be referred for evaluation and treatment by a variety of means. By adopting a contemporary view that facial growth is the result of genetic and environmental factors (some of which are functional), growth modification becomes a real possibility. Unfortunately, some problems must be camouflaged or treated by combined surgical and orthodontic means. Continued growth in early adulthood can enhance or detract from treatment results obtained in childhood or adolescence. These dynamic properties of the face make management of facial growth challenging but generally rewarding and successful because of substantial aesthetic and functional improvements. PMID- 1886738 TI - Structural abnormalities of the craniofacial complex and congenital malformations. AB - This article was meant to be a very cursory survey of the multiple defects that abnormal development can produce in all areas of the craniofacial complex. Careful examination for these abnormalities should lead the clinician to earlier referral of patients for additional examination by a genetics team. This often enables more focused care for the individual and better counseling concerning future pregnancies. Aase points out that "funny looking face" or "syndromic facies" is no longer helpful. Accurate assessment of the face with measurement leads to better diagnosis and ultimately better patient care. All children with facial defects deserve early intervention by a multidisciplined craniofacial team including geneticists, surgeons, dentists, speech pathologists, and other specialists. Part of the process of early referral to this team involves early detection and recognition in the neonatal period. It is hoped that this article stimulates the pediatrician to be aware of these abnormalities, recognize their importance, and seek additional help for patients, no matter what their age. PMID- 1886739 TI - Managing the cleft lip and palate patient. AB - We have attempted to elucidate, first through an examination of the basic science of clefting and then through a description of the roles of the various members of the cleft palate team, an understanding of the multiplicity of problems faced by this heterogeneous group of children with cleft lip or palate. With an incidence of cleft of 1 in 700 births, all practicing pediatricians will at some time be faced with a patient with a cleft. Pediatric management begins in the hospital nursery by ruling out possible associated anomalies (e.g., congenital heart disease or urinary tract) or syndromes. At the same time, cleft palate nursers may be needed to overcome feeding problems. Simultaneously, counseling for the family begins with a positive attitude toward outcome and an initial explanation of the schedule of corrective procedures, i.e., lip repair at 3 months of age and palate repair at about 1 year. The counseling should incorporate an understanding of the cause of clefting, both its genetics and teratogenetics, and then proceed to noting the actual recurrence risks of 1% for a new cleft and 16% if there is a positive family history in a first-degree relative. The recurrence risks in recognized syndromes may follow mendelian patterns. Later, the pediatrician can help the family deal with multiple ear infections and the likely need for tympanostomy tubes, anticipating the need for tubes in a way that might facilitate placement at the time of anesthesia for the lip or the palate repairs. An understanding of the speech and language difficulties that may be encountered in later infancy may relieve parental anxiety. Later, after palate repair, knowledge of velopharyngeal incompetence may avert premature hypernasal speech problems caused by adenoidectomy, which should be avoided if at all possible. The pediatrician needs to be aware of the tooth malformations that accompany clefting of the alveolus as well as the increased susceptibility to caries, so that the family may be directed to early intervention by the pediatric dentist. With support by pediatrics of the efforts of pediatric dentistry, the child is then in optimal condition for orthodontics. Continually keeping the child's emotional adjustment in mind, the pediatrician can encourage the child and family, knowing that with palatal expansion techniques plus possible bone graft surgery to the cleft alveolus at about 9 years of age, the child may be orthodontically corrected to very near normal.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1886740 TI - Identifying normal and abnormal development of dental occlusion. AB - Abnormalities of occlusal development manifest themselves clinically as a need for orthodontic treatment. There are many circumstances in which there is an interaction between traditional pediatric concerns and occlusal abnormalities. In some cases medical treatment impacts on the development of occlusion. In other cases, occlusal abnormalities contribute to clinical conditions seemingly far removed from the dentition. PMID- 1886741 TI - The role of the pediatrician in identifying and treating dental caries. AB - Although dental caries has been reduced greatly in the last two generations, this infectious disease persists. The pediatrician can play a direct and indirect role in preventing dental caries. The pediatrician can provide counseling on feeding practices to prevent baby bottle tooth decay as well as identify children at risk. Dental caries of the grooves of molar teeth now accounts for dental caries in more children than any other form of caries. Dental sealants are recommended to coat the grooves and prevent dental caries. Restoration of decayed teeth is the most direct means of treating dental caries. PMID- 1886742 TI - Periodontal health and disease in children and adolescents. AB - The prevention and treatment of periodontal diseases in children and adolescents are most desirable and the physician should be involved in the achievement of these goals. Furthermore, cooperation between the physician and the dentist may be imperative for the comprehensive treatment of some patients. One should be aware of the influence of the general growth and development of the periodontium in order to be able to differentiate between health and disease. Periodontal diseases in children and adolescents include chronic gingivitis, gingival recession, chronic periodontitis, prepubertal periodontitis, juvenile periodontitis, and cases with peculiar causes. The main cause for periodontal diseases is the microorganisms in the dental plaque. In addition, the systemic status of the individual may affect the response of the periodontal tissues and vice versa. The physician and dentist should cooperate with the purpose of providing comprehensive prevention, diagnosis, and treatment of periodontal diseases and systemic diseases. PMID- 1886743 TI - Preventive oral health care for the infant, child, and adolescent. AB - Although we have the knowledge and technology necessary to prevent it, most children experience dental disease, and a few children continue to experience high rates of decay. The appropriateness and effectiveness of preventive measures vary throughout the life of a child, and recommendations should be tailored to the needs of the individual. Water fluoridation continues to be the most cost effective preventive measure available. For patients who do not have access to fluoridated water, dietary supplementation offers similar benefits. A wide variety of professionally applied and home use topical fluoride products such as dentrifrices, gels, and rinses can also reduce the risk of dental caries, particularly on the smooth surfaces of the teeth. The most common site of decay in children is the fissures of the molar teeth. These areas can be protected by the professional application of plastic sealants. Dietary practices influence caries rates, and patients should be advised to limit the frequency of carbohydrate exposures rather than the total amount of carbohydrates consumed. Parents of infants should be advised to discontinue bottle feeding around the age of 12 months to avoid nursing caries. Although oral hygiene practices are not as effective in reducing caries rates as is generally believed, daily toothbrushing and flossing are unquestionably effective in preventing periodontal disease. In order to be maximally effective, preventive efforts should be initiated early in the life of the child. Although most children experience dental disease, a mouth free of caries and periodontal disease is a potentially attainable goal for all children when they use currently available techniques. PMID- 1886744 TI - Diagnosing and treating common oral pathologies. AB - When the physician is confronted with an oral pathologic condition in a child, the adage "common things happen commonly" should be applied. Congenital lesions such as palatal and alveolar cysts occur in almost 50% of newborns. Developmental conditions such as Fordyce granules and retrocuspid papillae are found in most children. Localized soft-tissue enlargements commonly seen in young children include the parulis, mucocele, papilloma, and inflammatory gingival tumors. In addition, soft-tissue pathologies and discomfort associated with herpesvirus infections or recurrent aphthous ulcerations often present as a chief complaint. The physician's knowledge and treatment recommendations for common oral pathologies should be an integral component to the overall medical management of infants, children, and adolescents. PMID- 1886745 TI - The pediatrician's involvement in prevention and treatment of oral disease in medically compromised children. AB - Significant oral health problems are associated with medical, physical, or mental disorders that occur in children. The pediatrician has the opportunity through early intervention to set the tone for a health care practice that will improve the quality of life for many disadvantaged children. When the pediatrician and pediatric dentist work hand in hand, the children can often expect a happy, healthy future. PMID- 1886746 TI - Oral habits. A behavioral approach. AB - Thumb-sucking, pacifier use, and other oral habits are not so harmful or beneficial to the child to justify ill-timed aggressive discontinuance. Indeed there is ample time to guide the child to forming desired behaviors. In nearly every case success in habit management depends on the child making a personal commitment to discontinue the habit. Control can be placed in the child's hands after that decision is made. PMID- 1886747 TI - Considerations in behavior management of the pediatric dental patient. Helping children cope with dental treatment. AB - Pediatric dentists use their knowledge of psychologic development and current theories of behavior modification to direct children in coping with the anxieties present at any dental visit. Only if these psychologic techniques are inadequate will conscious sedation, restraints, or general anesthesia be used to control children's behavior during dental treatment. This article emphasizes how dentists help children cope with dental treatment. PMID- 1886748 TI - Managing common dental problems and emergencies. AB - This article discusses the more common oral and dental emergencies that children and adolescents may present to a physician. Many of these problems represent true emergencies that require immediate treatment or referral, whereas others are more common and less critical problems perceived by the child's parents as needing immediate attention. The problems presented in this article fall into three general areas: gingival and soft-tissue-related problems; problems related to teeth; and traumatic injuries to the teeth, their roots, and supporting structures. PMID- 1886749 TI - [Role of MRI in diagnosis of adrenal tumors]. AB - The authors evaluated the ability of magnetic resonance imaging (MRI) at 1.5 T to characterize 33 adrenal masses, using visual analysis and the following quantitative variables: signal intensity ratios of tumor/liver, tumor/muscle, and (tumor--muscle)/(fat--muscle) on T2- and T1-weighted images, and the calculated T2 relaxation time of the adrenal masses. All 15 tumors of less than 3 cm in diameter were visually homogeneous on all pulse sequences, whereas the other 18 tumors of over 3 cm appeared to be inhomogeneous. The signal intensity ratios of tumor/liver and tumor/muscle and the calculated T2 relaxation time were not helpful in distinguishing tumors from one another. The ratios of tumor/fat and (tumor--muscle)/(fat--muscle) were useful in distinguishing pheochromocytoma and myelolipoma from other tumors on T2- and T1-weighted images, respectively. However, differentiation among other adrenal tumors appeared to be difficult. The authors concluded that, although MRI might have considerable potential in characterizing adrenal masses, the use of conventional MRI in such analysis is still quite limited. PMID- 1886750 TI - [Sonographic diagnosis of nonmalignant extrahepatic portal venous obstruction- incidence and background]. AB - We diagnosed nine cases of nonmalignant extrahepatic portal venous obstruction on ultrasonography at Kitakyushu Municipal Kokura Hospital between 1983 and 1989. Among 40544 cases of routine abdominal ultrasound study, nine cases of nonmalignant extrahepatic portal venous obstruction were found. The sonographic feature of "cavernous transformation" of the portal vein was noted at an incidence of about 1/2000. We classified these nine cases into three groups according to past history. Four cases underwent abdominal surgery. (Two had two operations). Three had abdominal inflammation or trauma, and two had no significant history, although one had taken oral contraceptive pills intermittently during the last ten years. PMID- 1886751 TI - [Adverse reactions to low osmolar iodine contrast media]. AB - From January 1989 to December 1989, we performed a prospective survey of adverse reactions to contrast media at three institutes of Juntendo University. We collected a total of 4365 case cards during the period. Low osmolar iodine contrast media were given in all but one case. Procedures using contrast media included computed tomography, intravenous urography, arteriography, venography and myelography. The overall incidence of adverse reactions was 6.6%, and there were no severe or fatal reactions. The incidence of adverse reactions was about the same in both sexes. However, in males, the incidence was higher in the fifth decade, and in females, it was higher in the third and seventh decades. There was no relation between the dose of contrast medium and adverse reactions. Intravenous bolus injections caused adverse reactions more often, followed by intra-arterial injections and then usual intravenous injections. The incidence of adverse reactions in patients with a history of allergy or previous reactions was higher. Pretesting was performed in 48.9% of the cases. PMID- 1886752 TI - [Radiologic manifestations of peritoneal mesothelioma]. AB - We report four cases of histologically proved peritoneal mesothelioma and describe the radiographic (mainly CT and angiographic) findings. There were three malignant diffuse tumors and one benign localized tumor. In one case, the lesion extended to the omentum and entrapped the fat tissue, and differentiation from peritonitis carcinomatosa was difficult. In the other three cases, reflecting necrotic change within the tumor, CT showed hypodensity throughout most of the mass. In two cases with hemorrhage, CT showed hyperdensity in the center of the mass. Angiography showed slight or medium neovascularity in the periphery of the tumor, but most of the tumor was avascular. Angiography was helpful for topographic diagnosis, but it was difficult to make a specific diagnosis or differentiate between malignant and benign types. We emphasize that it is important to consider peritoneal mesothelioma in the differential diagnosis when a mass of unknown origin is found in the abdomen, particularly when it is accompanied by necrosis and hemorrhage. PMID- 1886753 TI - [Value of "additional arterial embolization" to bilateral internal iliac TAE in patients with severe pelvic fractures]. AB - Transcatheter arterial embolization (TAE) of the bilateral internal iliac arteries has been shown to be of great value in controlling retroperitoneal massive hemorrhage associated with pelvic fractures. It has recently been reported, however, that TAE of only the bilateral internal iliac arteries sometimes fails to stabilize the patient's hemodynamics. The purpose of the present study was to evaluate "additional arterial embolization" to the bilateral internal iliac TAE in hemodynamically unstable cases. Sixty-eight patients who underwent emergency TAE following severe pelvic fractures were reviewed. Additional arterial embolization of the lumbar arteries in four patients, middle sacral arteries in two and inferior epigastric artery in one was carried out following bilateral internal iliac TAE. The damage to these arteries was associated with fractures of the lumbar costal process, sacrum, pubis, etc. The patients were in stable condition after the procedure, and no significant complication was experienced. When fractures and dislocations of the above mentioned bones are seen on plain X-ray films and arterial bleeding is identified by angiography, additional embolization of the arteries should be performed immediately. PMID- 1886754 TI - [Analysis of pyrophillitosis by high-resolution computed tomography]. AB - High-resolution computed tomography (HR-CT) was performed on 20 patients with pyrophilitosis. Small nodular opacities in these patients could be divided by HR CT into two types, namely, tiny irregular branching structures (TIB) and small round opacities (SRO). TIB had a centrilobular distribution and were characteristic of pyrophillitosis. SRO had both centrilobular and perilobular distributions and were considered to be changes modified by the aspiration of silica. Large opacities (LO) of pyrophillitosis were classified into three types, that is, spherical type, flat type parallel to the bronchus and flat type parallel to the thoracic wall. The spherical type was seen in patients exposed to both pyrophillite and silica, while the flat types were seen in patients exposed to only pyrophillite and were characteristic opacities of pyrophillitosis. Pulmonary emphysema was found in only one patient with pyrophillitosis, whereas mediastinal lymph node swelling and calcification were seen in most patients with pyrophillitosis. HR-CT is useful in making a more accurate evaluation of these lesions. PMID- 1886755 TI - [Study of early gastric cancer in upper third area of the stomach (C-area)]. AB - From January 1976 to March 1990, 802 cases of early gastric cancer (886 lesions) were underwent surgical resection at Himeji St. Mary's Hospital. Among them there were 74 cases (9.2%) of early gastric cancer (75 lesions (8.5%) in the C-area. In comparison with early gastric cancer found in the other 2 thirds of stomach, early gastric cancer in the C-area showed a higher incidence rate of the posterior wall lesions. This might be due to the reason why anterior wall lesions in the C-area were not fully displayed by routine radiological procedure. Since anatomically it is very difficult to study this area with the compression method, the thin layer method in the prone position should be recommended in addition to routine double contrast study. PMID- 1886756 TI - [Clinical results of N0 tongue cancer treated with interstitial brachytherapy and management of occult cervical node metastases]. AB - One hundred patients with T1-2NO squamous cell carcinoma of the oral tongue were treated with interstitial brachytherapy at the Hyogo Medical Center for Adults between 1962 and 1983. These patients were followed for more than two years. The cumulative five-year survival rate was 89% in T1N0 and 66% in T2N0. The relapse free survival rate was 88% in T1N0 and 51% in T2N0. The two-year local control rate in the primary site was 100% in T1N0 and 73% in T2N0. Cervical node metastases developed in 41% (T1N0: 33%, T2N0: 43%) of the patients. The five-year survival rate of the patients with subsequent cervical node metastases was 42%, while that of patients without subsequent cervical node metastases was 92% (p less than 0.001). Twenty-seven patients also received prophylactic neck irradiation (average dose: 33.8 Gy). In patients treated with prophylactic neck irradiation, the rate of subsequent cervical node metastases was 37% and the cumulative five-year survival rate was 62%. In the patients without prophylactic neck irradiation, these figures were 41% and 73%, respectively. There was no statistically significant difference between the two groups. Between 1984 and 1986, 28 patients with T1-2 N0 squamous cell carcinoma of the oral tongue were treated with interstitial brachytherapy. These patients were prospectively examined for the ability of chemotherapy to prevent the development of cervical node metastasis. In 13 patients treated with chemotherapy (CDDP 80 mg/m2 + PEP 6 mg/m2 x 5 days), the two-year local control rate was 90%, the incidence of cervical node metastases was 38% and the incidence of distant metastases was 15%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1886757 TI - [Intraarterial infusion of hypoxic radiosensitizer RK28 in rabbit VX2 tumor system]. AB - The effect of regional intra-arterial infusion of a hypoxic cell radiosensitizer RK28 (2-nitro-imidazole nucleoside analogue) on rabbit VX2 tumor was evaluated. Rabbits each weighing 2.5-3 kg were implanted with VX2 tumor in the left hind legs. Solid tumors grown up to 3 cm in diameter were treated with X-ray irradiation. Tumor volumes were assayed weekly by computed tomography (CT). Six rabbits were treated with 15 Gy of X-ray irradiation alone, and the other six rabbits were treated with intra-arterial infusion of RK28 (80 mg/kg) two minutes before 15 Gy of irradiation. The latter tumors regressed more rapidly than the former (p less than 0.01), and the latter rabbits seemed to survive longer than the former. The pharmacokinetics of RK28 and its metabolites in tumor tissue and serum were measured by high performance liquid chromatography (HPLC) using six rabbits. During irradiation, a high concentration of the agent was achieved in tumor tissue. It is suggested that a successful radiosensitizing effect will be obtained when regional intra-arterial infusion of RK28 is clinically combined with intraoperative radiation therapy and brachytherapy. PMID- 1886758 TI - Research on ethics in nursing education: an integrative review and critique. PMID- 1886760 TI - Why it should take six months to do an immediate denture. PMID- 1886759 TI - Directory of educational software for nursing. PMID- 1886761 TI - Evident diversity of codon usage patterns of human genes with respect to chromosome banding patterns and chromosome numbers; relation between nucleotide sequence data and cytogenetic data. AB - The sequences of the human genome compiled in DNA databases are now about 10 megabase pairs (Mb), and thus the size of the sequences is several times the average size of chromosome bands at high resolution. By surveying this large quantity of data, it may be possible to clarify the global characteristics of the human genome, that is, correlation of gene sequence data (kb-level) to cytogenetic data (Mb-level). By extensively searching the GenBank database, we calculated codon usages in about 2000 human sequences. The highest G + C percentage at the third codon position was 97%, and that of about 250 sequences was 80% or more. The lowest G + C% was 27%, and that in about 150 sequences was 40% or less. A major portion of the GC-rich genes was found to be on special subsets of R-bands (T-bands and/or terminal R-bands). AT-rich genes, however, were mainly on G-bands or non-T-type internal R-bands. Average G + C% at the third position for individual chromosomes differed among chromosomes, and were related to T-band density, quinacrine dullness, and mitotic chiasmata density in the respective chromosomes. PMID- 1886762 TI - Molecular heterogeneity of the fragile X syndrome. AB - The fragile X syndrome is an X-linked disorder which has been shown to be associated with the length variation of a DNA fragment containing a CGG trinucleotide repeat element at or close to the fragile site. Phenotypically normal carriers of the disorder generally have a smaller length variation than affected individuals. We have cloned the region in cosmids and defined the area containing the amplified sequence. We have used probes from the region to analyse the mutation in families. We show that the mutation evolves in different ways in different individuals of the same family. In addition we show that not all fragile X positive individuals show this amplification of DNA sequence even though they show expression of the fragile site at levels greater than 25%. One patient has alterations in the region adjacent to the CGG repeat elements. Three patients in fragile X families have the normal fragment with amplification in a small population of their cells. These observations indicate that there is molecular heterogeneity in the fragile X syndrome and that the DNA fragment length variation is not the only sequence responsible for the expression of the fragile site or the disease phenotype. PMID- 1886763 TI - Solid-phase synthesis of DNA fragments containing the modified base 7-hydro-8-oxo 2'-deoxyguanosine. AB - The 5'-(4,4'-dimethoxytrityl) protected 3'-(2-cyanoethoxy)-N,N diisopropylphosphoramidite of 7-hydro-8-oxo-2'-deoxy-guanosine, the exocyclic amino and lactam functions of which are protected with acetyl and diphenylcarbamoyl groups, respectively, has been prepared from the 8-bromo derivatives of deoxy- and riboguanosine. This synthon, in combination with standard d-nucleoside 3'-(2-cyanoethoxy)-N,N-diisopropylphosphoramidites, was applied successfully to a solid-phase synthesis. Well-defined oligodeoxyribonucleotides containing a 7-hydro-8-oxo-2'-deoxyguanosine residue at predetermined positions were obtained after deprotection with methanolic ammonia and purification by gel filtration. PMID- 1886764 TI - A novel and rapid method for isolating sequences adjacent to rare cutting sites and their use in physical mapping. AB - We describe a simple PCR based technique which can be used to isolate sequences adjacent to rare cutter sites and can subsequently be employed for the construction of long range physical maps. The method involves the ligation of an adaptor to rare cutter sequences and its use as a target for forward priming in PCR. Primers to Alu repeat elements initiate synthesis of the reverse strand. Using this technique any rare cutter site which has a repeat element within amplification range can be cloned. We have isolated six unique sequences around NotI sites from an irradiation reduced hybrid containing a fragment of human chromosome 22 and are using these for physical mapping around the Ewing's sarcoma translocation breakpoint on chromosome 22. PMID- 1886765 TI - Reinvestigation of DNA ligase I in axolotl and Pleurodeles development. AB - We have recently shown that the exclusion process causing the replacement of DNA ligases II by DNA ligase I in amphibian eggs after fertilization does not occur in the case of Xenopus laevis [Hardy, S., Aoufouchi, S., Thiebaud, P., and Prigent, C., (1991) Nucleic Acids Res. 19, 701-705]. Since this result is in contradiction with the situation reported in axolotl and Pleurodeles we decided to reinvestigate such results in both species. Three different approaches have been used: (1) the substrate specificity of DNA ligase I; (2) the DNA ligase-AMP adduct reaction and (3) the immunological detection using antibodies raised against the X.laevis DNA ligase I. Our results clearly demonstrate that DNA ligase I activity is associated with a single polypeptide which is present in oocyte, unfertilized egg and embryo of both amphibians. Therefore, the hypothesis of a change in DNA ligase forms, resulting from an expression of the DNA ligase I gene in axolotl and Pleurodeles early development must be rejected. We also show that, in contradiction with published data, the unfertilized sea urchin egg contains a DNA ligase activity able to join blunt ended DNA molecules. PMID- 1886766 TI - Activation of IFN-beta element by IRF-1 requires a posttranslational event in addition to IRF-1 synthesis. AB - Expression of the Type I IFN (i.e., IFN-alpha s and IFN-beta) genes is efficiently induced by viruses at the transcriptional level. This induction is mediated by at least two types of positive regulatory elements located in the human IFN-beta gene promoter: (1) the repeated elements which bind both the transcriptional activator IRF-1 and the repressor IRF-2 (IRF-elements; IRF-Es), and (2) the kappa B element (kappa B-E), which binds NF kappa B and is located between the IRF-Es and the TATA box. In this study we demonstrate that a promoter containing synthetic IRF-E, which displays high affinity for the IRFs can be efficiently activated by Newcastle disease virus (NDV). In contrast, such activation was either very weak or nil when cells were treated by IFN-beta or tumor necrosis factor-alpha (TNF-alpha), despite the fact they both efficiently induce de novo synthesis of the short-lived IRF-1 in L929 cells. In fact, efficient activation of the IRF-E apparently requires an event in addition to de novo IRF-1 induction, which can be elicited by NDV even in the presence of protein synthesis inhibitor, cycloheximide. Moreover, efficient activation of the IRF-E by NDV is specifically inhibited by the protein kinase inhibitor, Staurosporin. Hence our results suggest the importance of IRF-1 synthesis and post-translational modification event(s), possibly phosphorylation for the efficient activation of IRF-Es, which are otherwise under negative regulation by IRF-2. PMID- 1886767 TI - A self-splicing group I intron in the nuclear pre-rRNA of the green alga, Ankistrodesmus stipitatus. AB - The nuclear small subunit ribosomal RNA gene of the unicellular green alga Ankistrodesmus stipitatus contains a group I intron, the first of its kind to be found in the nucleus of a member of the plant kingdom. The intron RNA closely resembles the group I intron found in the large subunit rRNA precursor of Tetrahymena thermophila, differing by only eight nucleotides of 48 in the catalytic core and having the same peripheral secondary structure elements. The Ankistrodesmus RNA self-splices in vitro, yielding the typical group I intron splicing intermediates and products. Unlike the Tetrahymena intron, however, splicing is accelerated by high concentrations of monovalent cations and is rate limited by the exon ligation step. This system provides an opportunity to understand how limited changes in intron sequence and structure alter the properties of an RNA catalytic center. PMID- 1886768 TI - Genomic organization and chromosomal mapping of the mouse P-cadherin gene. AB - Cadherins are a family of Ca(2+)-dependent cell adhesion molecules, that includes P-cadherin, E-cadherin, N-cadherin and L-CAM. In this study, the genomic organization of the mouse P-cadherin gene was determined by analyzing overlapping DNA clones obtained from a mouse genomic library. The results showed that this gene spans over 45 kb and consists of 15 exons. A marked feature of this gene is that the first intron is 23 kbp long accounting for half its length. Comparisons of this structure with that of L-CAM, a chicken cadherin, revealed that the exon intron boundaries are conserved between the two genes except that the P-cadherin first exon includes the correspoding first and second exons of the L-CAM gene. This gene was also similar to the other in that the second intron, which corresponds to the P-cadherin first intron, is exceptionally longer than other introns. These results suggest that the exon-intron pattern conserved in these genes is of significance for generation of domain structure of cadherin molecules or for their transcriptional regulation. We also determined the chromosomal localization of the P-cadherin gene by interspecific backcross analysis, and found that this gene is located in the central region of mouse chromosome 8 and linked with the E-cadherin locus. This is the first evidence for the linkage of different cadherin genes. PMID- 1886769 TI - Transcription factors binding to the mouse HTF9 housekeeping promoter differ between cell types. AB - The mouse CpG island HTF9 harbours a bidirectional promoter shared by two housekeeping genes that are arranged head-to-head. We have previously identified several protein binding-elements across the CpG island, yet a short region around the initiation region was found to be capable of bidirectional transcription in transient expression assays, suggesting that the multiple elements of the HTF9 promoter are functionally redundant. We have now compared the binding activities in nuclear extracts from different cell types. Two protein-binding elements of HTF9 interact with widely distributed factors. A potentially strong Sp1 binding site was also identified, however Sp1 appeared to bind efficiently to its target sequence with extracts prepared from proliferating cultured cells, but not from adult organs. On the other hand, the CCAAT box upstream of one gene (HTF9-A) interacted with a liver-enriched factor, whereas no binding was detected with cultured fibroblasts extracts. Consistently, deletion of the CCAAT box affected transient expression from the HTF9-A promoter in hepatocyte, but not in fibroblast, cultures. Our results suggest that ubiquitous expression of housekeeping promoters results from the activation of alternative elements in different cell types. PMID- 1886770 TI - Monoclonal antibody-based, selective isolation of DNA fragments containing an alkylated base to be quantified in defined gene sequences. AB - We have established a sensitive, monoclonal antibody (Mab)-based procedure permitting the selective enrichment of sequences containing the miscoding alkylation product O6-ethylguanine (O6-EtGua) from mammalian DNA. H5 rat hepatoma cells were reacted with the N-nitroso carcinogen N-ethyl-N-nitrosourea in vitro, to give overall levels of greater than or equal to 25 O6-EtGua residues per diploid genome (corresponding to O6-EtGua/guanine molar ratios of greater than or equal to 10(-8). For analysis, enzymatically restricted DNA from these cells is incubated with an antibody specific for O6-ethyl-2'-deoxyguanosine, the resulting Mab-DNA complexes are separated from (O6-EtGua)-free fragments by filtration through a nitrocellulose (NC) membrane, and the DNA is recovered from the filter bound complexes quantitatively. The efficiency of Mab binding to DNA fragments containing O6-EtGua is constant over a range of O6-EtGua/guanine molar ratios between 10(-5) and 10(-8). (O6-EtGua)-containing restriction fragments encompassing known gene sequences (e.g., the immunoglobulin E heavy chain gene of H5 rat hepatoma cells used as a model in this study) are subsequently amplified by PCR and quantified by slot-blot hybridisation. The content and distribution of a specific carcinogen-DNA adduct in defined sequences of genomic DNA can thus be analyzed as well as the kinetics of intragenomic (toposelective) repair of any DNA lesion for which a suitable Mab is available. PMID- 1886771 TI - Human uracil-DNA glycosylase complements E. coli ung mutants. AB - We have previously isolated a cDNA encoding a human uracil-DNA glycosylase which is closely related to the bacterial and yeast enzymes. In vitro expression of this cDNA produced a protein with an apparent molecular weight of 34 K in agreement with the size predicted from the sequence data. The in vitro expressed protein exhibited uracil-DNA glycosylase activity. The close resemblance between the human and the bacterial enzyme raised the possibility that the human enzyme may be able to complement E. coli ung mutants. In order to test this hypothesis, the human uracil-DNA glycosylase cDNA was established in a bacterial expression vector. Expression of the human enzyme as a LacZ alpha-humUNG fusion protein was then studied in E. coli ung mutants. E. coli cells lacking uracil-DNA glycosylase activity exhibit a weak mutator phenotype and they are permissive for growth of phages with uracil-containing DNA. Here we show that the expression of human uracil-DNA glycosylase in E. coli can restore the wild type phenotype of ung mutants. These results demonstrate that the evolutionary conservation of the uracil-DNA glycosylase structure is also reflected in the conservation of the mechanism for removal of uracil from DNA. PMID- 1886772 TI - Unusual conformation of (dA)n.(dT)n-tracts as revealed by cyclobutane thymine thymine dimer formation. AB - Cyclobutane dimer formation has been used to probe conformation of (dA)n.(dT)n tracts cloned in plasmid DNA. The observed dimer probability patterns for (dA)n.(dT)n-tracts with n greater than or equal to 4 exhibit maximum intensity at the 3'-terminal TT site of Tn-tract, whereas photoreactivity at all the other TT sites is inhibited. Both the temperature and dimethyl sulfoxide increase dimer formation within Tn-tracts and result in an even dimer pattern. The data obtained have been interpreted in terms of an unusual structure adopted by (dA)n.(dT)n tracts. An influence of flanking base pairs, ethidium bromide binding and ionic strength has also been studied. PMID- 1886773 TI - Repression of the murine interferon alpha 11 gene: identification of negatively acting sequences. AB - The uninducible murine interferon alpha 11 gene (Mu IFN-alpha 11) shows strong homology with the highly inducible Mu IFN-alpha 4 gene in the promoter region. Negative regulatory sequences located between positions -470 and -145 were characterized in the Mu IFN-alpha 11 promoter. The removal of these sequences leads to virus-inducibility of Mu IFN-alpha 11 while their insertion in Mu IFN alpha 4 corresponding region significantly reduced the inducibility of Mu IFN alpha 4 promoter. On the other hand, the virus-responsive element (VRE) of the Mu IFN-alpha 11 differs by a single nucleotide substitution at position -78 from the VRE alpha 4. Constructions carrying either VRE alpha 11 or VRE alpha 4 upstream a heterologous promoter displayed different virus inducibilities. The -78 A/G substitution affects the inducibility by decreasing the affinity of VRE-binding trans-regulators. Our results suggest that the combined effect of the negative regulatory sequences and of the mutation in the VRE alpha 11, completely silences the Mu IFN-alpha 11 gene. PMID- 1886774 TI - Stringent integrity requirements for both trans-activation and DNA-binding in a trans-activator, Oct3. AB - POU-specific and POU-homeo domains of Oct3 were produced in Echerichia coli for characterization of DNA binding to the octamer sequence. POU domain protein including A, B and H domains could bind to the octamer sequence efficiently and specifically, and DNase I footprint analysis gave an indistinguishable protection pattern between recombinant POU protein of Oct3 and native Oct3 from undifferentiated P19 cells. Truncated mutants, which contained B-specific and H domains or the H domain only, showed no binding activity, indicating that both of POU-specific and POU-homeo domains are essential for binding activity to octamer sequence. Furthermore, a 6 amino acid deletion from the N-terminal region of the A-specific domain is enough to destroy the binding activity. As for trans activation, the N-terminal region is essential and sufficient. Deletion of the N terminal proline-rich region rapidly eliminated trans-activating activity. These data strongly indicate the stringent integrity requirements for both trans activation and DNA-binding domains in Oct3. PMID- 1886775 TI - Structure of the human gene for monoamine oxidase type A. AB - Monoamine oxidases, type A and type B, are principal enzymes for the degradation of biogenic amines, including catecholamines and serotonin. These isozymes have been implicated in neuropsychiatric disorders. Previously, cDNA clones for both MAO-A and MAO-B have been sequenced and the genes encoding them have been localized to human chromosome Xp11.23-Xp11.4. In this work, we isolated human genomic clones spanning almost all the MAOA gene from cosmid and phage libraries using a cDNA probe for MAO-A. Restriction mapping and sequencing show that the human MAOA gene extends over 70 kb and is composed of 15 exons. The exon structure of human MAOA is similar to that described by others for human MAOB. Exon 12 (bearing the codon for cysteine, which carries the covalently bound FAD cofactor) and exon 13 are highly conserved between human MAOA and MAOB genes (92% at the amino acid level). Earlier work revealed two species of MAO-A mRNA, 2.1 kb and 4.5-5.5 kb. We now report on further cDNA isolation and sequencing, which demonstrates that the longer message has an extension of 2.2 kb in the 3' noncoding region. This extended region is contained entirely within exon 15. The two messages therefore appear to be generated by the use of two alternative polyadenylation sites. Results from the present work should facilitate the mutational analysis of functional domains of MAO-A and MAO-B. Knowledge of the gene structure will also help in evaluating the role of genetic variations in MAO A in human disease through the use of genomic DNA, which is more accessible than the RNA, as a template for PCR-amplification and sequencing. PMID- 1886776 TI - Influence of DNA topology and histone tails in nucleosome organization on pBR322 DNA. AB - Recently, we have found that the assembly of nucleosomes reconstituted on negatively supercoiled DNA is cooperative. In the present paper the role of DNA topology and of histone tails in nucleosome assembly was explored. Reconstituted minichromosomes on relaxed DNA at different histone/DNA ratios (R) were assayed by topological analysis and electron microscopy visualization. Both methods show a linear relationship between average nucleosome number (N) and R. This suggests that in the case of relaxed DNA, cooperative internucleosomal interactions are small or absent. The influence of histone tails in nucleosome assembly was studied on minichromosomes reconstituted with trypsinized histone octamer on negatively supercoiled DNA by topological analysis. The topoisomers distribution, after trypsinization, dramatically changes, indicating that nucleosome-nucleosome interactions are remarkably decreased. These results show that, in chromatin folding, in addition to the well known role of histone H1, the interactions between histone octamer tails and DNA are also of importance. PMID- 1886777 TI - Nucleotide sequence of human elongation factor-1 beta cDNA. PMID- 1886778 TI - Complete nucleotide sequence of a gene encoding the 70 kd heat shock protein of Mycobacterium paratuberculosis. PMID- 1886779 TI - HTF4: a new human helix-loop-helix protein. PMID- 1886780 TI - DNA fingerprinting by specific priming of concatenated oligonucleotides. PMID- 1886781 TI - Improved site-directed mutagenesis method using PCR. PMID- 1886782 TI - General method for direct cloning of DNA fragments generated by the polymerase chain reaction. PMID- 1886783 TI - A simple method for introducing a thiol group at the 5'-end of synthetic oligonucleotides. PMID- 1886784 TI - Simplified method for confirmation of PCR products. PMID- 1886785 TI - A new polymorphic probe on chromosome 3p: lambda LIB46-27' (D3S635). PMID- 1886786 TI - A new polymorphic probe on chromosome 3p: lambda LIB27-98" (D3S1096). PMID- 1886787 TI - A new polymorphic probe on chromosome 3p: lambda LIB45-86 (D3S633). PMID- 1886788 TI - A new polymorphic probe on chromosome 3p: lambda LIB27-77 (D3S603). PMID- 1886789 TI - A new polymorphic probe on chromosome 3p: lambda LIB39-63 (D3S616). PMID- 1886790 TI - A new polymorphic probe on chromosome 3p: lambda LIB50-50' (D3S1099). PMID- 1886791 TI - A new polymorphic probe on chromosome 3p: lambda LIB36-68 (D3S615). PMID- 1886792 TI - PCR detection of a repeat polymorphism within the F7 gene. PMID- 1886793 TI - PCR detection of a HindIII polymorphism in the human gene for type II procollagen (COL2A1). PMID- 1886794 TI - Trinucleotide repeat polymorphism at the human gamma-B-crystallin gene. PMID- 1886795 TI - A polymorphic microsatellite repeat sequence on chromosome 21 (D21S80). PMID- 1886796 TI - PstI polymorphism within the 3' untranslated region of the insulin gene detectable by the polymerase chain reaction (INS). PMID- 1886798 TI - Final choices. PMID- 1886799 TI - Welsh care bid. PMID- 1886800 TI - Dear UKCC... PMID- 1886801 TI - Endangered occupation. PMID- 1886797 TI - New nucleotide sequence data on the EMBL File Server. PMID- 1886802 TI - Nothing special? PMID- 1886803 TI - Nursing reflections. PMID- 1886804 TI - Assessing with care. PMID- 1886805 TI - The prayer. PMID- 1886806 TI - Just chatting. PMID- 1886807 TI - Total knee replacement. Care study. PMID- 1886808 TI - Making sense of ... the Sengstaken tube. AB - Oesophageal haemhorrage is a life-threatening condition, but it can be stemmed by the use of the Sengstaken tube. Patricia McCaffrey explains the technique for insertion and the need to monitor the patient. PMID- 1886809 TI - Transient neonatal diabetes. PMID- 1886810 TI - MIETS meets needs. PMID- 1886811 TI - Real nurses don't go mad. PMID- 1886813 TI - Welsh in a bilingual health-care setting. PMID- 1886812 TI - Arts in action. Art's delight. PMID- 1886814 TI - Patient involvement in nursing decisions. PMID- 1886815 TI - Journal of Wound Care Nursing. Dressing burns in children. PMID- 1886816 TI - Journal of wound care nursing. Comparing Norton and Medley. PMID- 1886817 TI - AIDS specialist to visit USSR. PMID- 1886818 TI - Journal of Wound Care Nursing. Examining hydrocolloids. PMID- 1886819 TI - Journal of Wound Care Nursing. Using proper protocol. PMID- 1886820 TI - Workers slam AIDS charter. PMID- 1886821 TI - Journal of Wound Care Nursing. A new dressing for pressure sores. PMID- 1886822 TI - Journal of Wound Care Nursing. Choosing a dressing. PMID- 1886823 TI - Group effect on parental rating of acceptability of behavioral management techniques used in pediatric dentistry. AB - The rating of acceptability by parents either in groups of five or alone of behavior management techniques (BMT) displayed in videotaped vignettes was studied. Ratings of acceptability of the techniques for use on "a" vs. "their" child also were evaluated. Sixty parents were divided randomly into two groups (A and B). For Group A, six groups of five parents viewed a videotape containing eight BMT. All parents in Group B viewed the same videotape individually. Following the presentation of each BMT, the parents were requested to rate the technique for acceptability using a visual analogue scale (VAS). One half of Groups A and B were told to rate the acceptability of each BMT for use on "a" child. The remaining parents in Groups A and B were told to rate the acceptability for "their" child. The results indicated that there were no significant differences between groups (groupings of five vs. alone) or "their" and "a" child ratings. However, there was a consistent trend for those in groups to rate BMT as less acceptable than those rating alone. The implications of these findings are discussed in reference to findings of previous studies. PMID- 1886824 TI - An in vitro comparison of acid etched vs. nonacid etched dentin bonding agents/composite interfaces over primary dentin. AB - The purpose of this study was to evaluate acid etchant penetration on dentin bonding agents and its effect on the composite resin bond strength. Forty primary molars were mounted, then the buccal and lingual surfaces were prepared into dentin. The teeth were divided into four groups of 10, and four dentin bonding agents were placed on the buccal and lingual surfaces of exposed dentin, as recommended by the manufacturers. One surface of each tooth was etched randomly for 60 sec with 35% phosphoric acid. A standardized tube of composite resin was placed on each dentin surface and polymerized for 60 sec. The tubes were sheared off with an Instron Testing Machine. The specimens then were sectioned to be examined by a scanning electron microscope (SEM). Results demonstrated shear strengths (kg/cm2) of etched (e) and unetched (u) bonding agents to be: Scotchbond (3M Dental Products, St. Paul, MN) (e) 116.7 +/- 37.7, (u) 116.7 +/- 63.0; Scotchbond 2 (3M Dental Products, St. Paul, MN) (e) 112.0 +/- 40.6, (u) 127.0 +/- 38.7; Gluma (Bayer Dental, Leverkusen, Federal Republic of Germany) (e) 80.1 +/- 21.7, (u) 107.0 +/- 16.6; Bondlite (Kerr Manufacturing Co., Romulus, MI) (e) 53.4 +/- 34.7, (u) 79.1 +/- 26.3. The analysis of variance (ANOVA) demonstrated a statistical significance in variance at the P less than 0.001 level. Scheffe's Test indicated no statistically significant differences between the bond strengths of etched vs. nonetched dentin bonding agents and composite resin. SEM evaluation indicated that the acid etchant penetrated none of the dentin bonding agents. PMID- 1886825 TI - Macroscopic enamel defects of primary anterior teeth--types, prevalence, and distribution. AB - A total of 40.7% of 509 exfoliated primary anterior teeth from children who were healthy products of uneventful pregnancies exhibited at least one macroscopic enamel defect. Twenty percent of the teeth exhibited hypoplastic defects (HD), 12.4% exhibited white-cream opacities (WCO), and 9.8% exhibited yellow-brown opacities (YBO). Slightly more than a third (33.6%) of the teeth had defects we considered to be developmental enamel defects (DED). The occurrence of DED did not vary with gender, side of mouth, individual tooth types, or racial background. DED occurred with increased frequency on maxillary teeth, facial surfaces, and the middle third of affected surfaces. These locations have thicker enamel than other sites and may be more susceptible to insult if vulnerability is a function of metabolic demand of the rapidly secreting ameloblasts. Twenty-five per cent of the maxillary incisors and 10.1% of the mandibular incisors exhibited HD whose locations coincided with enamel forming at birth. A third (33.3%) of the canines exhibited HD, which occurred most commonly in the middle third of the facial surfaces. These defects are believed to occur approximately six months postnatally and may be primarily due to mechanical trauma. YBO most commonly occurred on the middle third of the facial surfaces, while WCO on the gingival third. Neither YBO nor WCO followed a chronologic pattern. PMID- 1886826 TI - Aspartame and dental caries in the rat. AB - Aspartame (NutraSweet--The NutraSweet Co., Deerfield, IL) an artificial intense sweetener, was tested for its cariogenicity alone and in the presence of sucrose. Sprague-Dawley rat pups (Charles River Laboratories, Bloomington, MA) inoculated with Streptococcus mutans were fed basal diet 2000 with one of the following added: 50% sucrose; 30% sucrose; 30% sucrose + 0.15% aspartame; 0.30% aspartame; 0.15% aspartame and no addition. The animals were sacrificed after eight weeks. Caries was evaluated using Keyes' technique. It was found that the addition of 0.15% aspartame to 30% sucrose diet significantly reduced caries in comparison to rats fed only 30% sucrose diet. In animals fed aspartame only, there was no caries. The S. mutans counts were high in the animals receiving sucrose diets with and without aspartame. The animals receiving only aspartame had very low S. mutans counts. PMID- 1886827 TI - Sialolithiasis in an 8-year-old child: case report. AB - Sialolithiasis rarely occurs in children; it is observed more commonly in adults. Various treatment modalities for sialolithiasis have been reported in the world dental and medical literature; most rely upon surgical intervention. This case report demonstrates that surgical intervention is not always indicated. We describe an 8-year-old child with a sialolith in the posterior third of Wharton's duct which spontaneously passed from the duct. Clinical findings, etiology and treatment of sialolithiasis are reviewed. PMID- 1886828 TI - Override of an N2O/O2 machine fail-safe mechanism: case report. PMID- 1886829 TI - Labial talon cusp in a child with incontinentia pigmenti achromians: case report. PMID- 1886830 TI - More than one factor can influence caries development in HIV-positive children. PMID- 1886831 TI - [Aging and periodontal disease. Clinical study of gingival recession]. AB - Gingival mucus in an older patient is the site of the slowing-down of the cellular turnover, of a lessening of metabolic activity and of keratinisation. The resistance to mechanical attacks and bacteria lessens thus its potential for repair. Thus one notes a worsening state of parodontal complaints during old age. By means of a study carried out at the Clinique de Parodontie of the Institut d'Odonto-Stomatologie in Dakar, we propose to attempt to see if the presence of gingival retraction can be linked with parodontal senescence by means of observing 318 patients. PMID- 1886832 TI - [Complete removable dentures and the elderly at I.O.S., Dakar]. AB - INTRODUCTION: At I.O.S. Dakar, we have taken an essential interest in elderly persons with functional disorders, aesthetic and psychological. We have fixed the following objectives: to evaluate the importance of the elderly person in our surgery to define the major characteristics of this category of patient to single out the specific aspects of the restorative denture to make our teaching programmes more relevant. MATERIALS AND METHODS: Two complementary axes: a retrospective statistical descriptive study carried out on the records of patients at P.A.C. of I.O.S. during the previous three academic years of patients at P.A.C. of I.O.S. during the previous three academic years 1986-87, 88-89, 89 90. an analysis of the records based on the following variables: age, sex, place of living, occupation, type of complete attached dentures additionally, certain particular aspects of these patients have been studied. SELECTION CRITERIA: We have studied patients over 55 years of age who have either a single or bimaxillary replacement. VARIABLES STUDIED: two types of denture: unimaxillary CAD and bimaxillary CAD our patients were classed as: urban--living in Dakar and Goree rural--coming from surrounding villages suburban--those coming from Pikine, Parcelles Assainies, Rufisque. for occupation: first sector--agriculture, fishing second sector--industrial or conversion workers third sector--service workers or tradesmen, housewives, pensioners, others. RESULTS AND COMMENTARY: the sex ratio is closely akin to that of the general population the majority of patients live in Dakar these are mainly housewives, retired people who could regularly attend our consultations and stay the course of our treatment, prosthetic restorations are complete attached bimaxillary dentures (79.14%). Clinical specifications: On a local clinical level, the total toothlessness of the elderly presents as: a muscular hypotomy, a loss of the vertical dimension of occlusion, a marked increase in nasal and oral fissures, a stiffening of the articular structures, a great reduction of osteo-mucus in the residual edges, a spreading of the tongue which invades the oral cavity, a loss of occlusive memory, Bearing on therapy and teaching: good clinical observation, constant reference to the medical services, appropriate surgery prior to denture fitting. CONCLUSION: This study shows us that at I.O.S. Dakar, persons over 55 coming to consult us are most often city dwellars and often housewives or retired people. The major purpose of these visits is functional. The minute failure rate encountered over these three years has led us to believe that prosthesis enjoys high esteem thanks to the raised criteria of competence, of knowledge and of the patience of the whole team. PMID- 1886833 TI - [Clinical use of the Sonic Air MM 1500 and the Meca Sonic 1400 in canal preparation in endodontics]. AB - INTRODUCTION: The preparation for canalisation has remained manual for a long time, technically constrictive and lasting for a long time. The application of ultrasound in Endontony allows us to tackle more calmly the canal course of the teath. The aim of this work is to make a qualitative comparison of the endosonic technique and the manual technique with reference to cases treated in the Dentisterie Operatoire clinic in Dakar. MATERIAL AND METHOD: 40 teeth of a complex canal anatomy and or in the posterior position in the buccal cavity were submitted to either a manual canalisation preparation or endosconic followed by monconic canal filling with a paste: 3 inc oxyde eugenol and iodoform. OPERATING FORMULA: Preparatory X rays: Allow us to evaluate the length of the work or the operating length after catheterisation: LO--length PRO, APEX RADIO-IMM LO- operating length PRO - occlusive point of reference The parietal support technique: The "synergetic" effect of ultrasonic oscillations of cavitation and of micro-acoustic currents associated with the action of the irrigation solution allow us to obtain canal incision. INSTRUMENTS: the pneumatic Sonic Air MM 1500; the Meca Sonic MMR 1400 coupled to a standard ISO motor; SHAPERS and Meca Shapers. Activated by shaper or Meca Shaper. Classic monoconic canal filling: Wadding paste + zinc oxyde paste-iodoform eugenol. X rays for orthocentric monitoring. RESULTS--DISCUSSION: In 60% of the cases treated, the patients presented with a complete dentition. The third inferior molar was in almost all the cases, the cause of the patient seeking a dental consultation. By endosonic treatment-conservation of teeth which would otherwise have been destined for extraction; biopulectomy or instituted pulpectomy for cases of desdodontite, endosconic amplication and canal sealing after the cooling of the inflammation. Duration of treatment: 2 sessions for gangrenous cases or desmodondite and one session for biopulpectomy or pulpectomy, with 4 sessions in 10% of the cases. Operation times: Saving of time of 40-50%. If a second session was necessary, 15 20 minutes was sufficient. Incidents or accidents during or after the operation: breakage of instruments, post-operative inflammatory reaction. CONCLUSION: better distribution of the irrigation solution, lessening of the risk of infection, better quality of the state of the canal surface, reduction in operating time, precision and reliability, conservation of teeth which would otherwise have been extracted, as many of the elements which encourages the appreciation of ultrasound in endodonty. PMID- 1886834 TI - [Surgical prosthetic approach to sequelae of a case of noma involving half the face]. AB - In this study, the authors discuss a prosthetic rehabilitation case resulting from loss of substance due to Noma. The dental prosthesis is made from tinted acrylic resin with a combination of two means of retention. The lower mean of retention is composed of a hook leaning on a handle which has been attached to that end on a metal armature and the upper mean of retention is connected to the bridge of spectacles. PMID- 1886835 TI - [Surgical dentistry and geriatrics in Senegal]. AB - INTRODUCTION: Geriatric medicine is developing more and more as a specialism. Odontology is not behindhand. That is why, even in an African setting, when life expectancy is still not as high as in the West, we are finding ourselves treating older and older patients. MATERIALS AND METHODS: During the course of the academic year 1989-1990, we treated 40 patients of both sexes, of different ethnic and social backgrounds aged from 55-89 years. Besides age, the patients had all undergone endo-buccal surgery, with the exception of parodontology surgery. According to sex: The forty patients comprised 27 men and 13 women. These figures are interesting and we will return to them during the discussion. According to age: The ages of our patients ranged from 55-89 years, with an average of 72. The distribution of age brackets shows a strong percentage (52.5%) of patients between 55 and 64 years of age. According to oral stage: In general, our patients neglect oral hygiene: 67.5% presented at least tartaric gingivitis. This negligence was evident in more men than women. According to general state: More than half the sample had at least one general pathological disorder. They ranged from cardio-vascular ailments, to differing digestive disorders, to neurological and endocrinal pathologics. METHODOLOGY: The data was collected using the following 3 methods which slowly built up: questionnaire clinical examination the operation RESULTS: The dividing-up of the different operations: we realised a total of 71 operations, this being an average 1.77 per patient. Distribution of pathological ailments according to type and nature: About 55% of our patients had a general pathology. Cardio-vascular ailments took first place with a frequency of 52.16%, followed by digestive problems with 26.08% neurological syndromes with 13.04% and ailments with endocrinal origins with a rate of 8.69%. Incidents during operation: incidents linked to the anaesthetic, incidents linked to the operation itself, post-operative incidents, healing. DISCUSSION: Age: The most representative age-band was between 55 and 64 years (with a six ration of 1:5). Multiple extractions: Apart from a defective oral state, these extractions are always motivated by the need for prosthesis. All the patients were missing at least one tooth, confirming the thesis of Dubois, according to which "the repercussion of oral ageing appears in all its simplicity in either partial or total toothlessness". CONCLUSION: Elderly Senegalese patients present serious oral problems since extraction comprises the main part of surgical odontological operations. A better way of dealing with these subjects, weakened by old age and general pathology, is desirable. PMID- 1886836 TI - Chronic mental illness in adolescence: a global overview. AB - In countries where it has been studied, between 10 and 15% of adolescents appear to have an emotional disorder, and an additional 5-10% have significant emotional symptomatology. Despite this prevalence, pediatricians appear poorly trained to identify children with emotional and behavioral problems. This paper focuses on schizophrenia, affective and chronic stress disorders. Schizophrenia in adolescence has a reported prevalence ranging from 0.9/10,000 hospital admissions for adolescents in Great Britain to 0.4% of cases in a university setting in the United States. For affective disorders, studies have placed the prevalence rates at nearly 3% for boys and almost double that for girls. A much larger percent of adolescents have significant depressive symptomatology. Many youths grow up in chronically stressful environments. This paper reviews the prevalence as well as the major diagnostic and prognostic issues, for the leading chronic mental health disorders of youth. PMID- 1886837 TI - Outpatient-based transition services for youth. AB - There is a paucity of information on the process of transition from pediatric to adult services for young people with chronic disease/disability. Adolescents and young adults have differing needs from children and older adults, and ideally transition services should take these needs into account. Diabetes provides a useful model to examine the process of transition and to seek views of young people. A study of 70 young adults with diabetes is reported. It is suggested that the ideal time for a transfer from a pediatric to an adult service is between 17 and 20 years, but this will vary considerably depending on developmental needs. Specialist physicians remain the most important professionals in the view of the young diabetics, who valued the physician as one to whom they can relate and get to know well by seeing regularly. The role of educational programs and help with psychosocial problems at this age are discussed in the light of conflicting evidence in the literature. PMID- 1886838 TI - Variations in endogenous viral gene patterns in White Leghorn, medium heavy, White Plymouth Rock, and Cornish Chickens. AB - The endogenous viral (ev) gene patterns of White Leghorn (WL; 6 lines), medium heavy (MH; 4 lines), White Plymouth Rock (WPR; 8 lines), and Cornish types (2 lines) of commercial chickens were compared. Southern blot analysis of SstI digested genomic DNA of 151 chickens revealed that the number of ev gene containing fragments in a chicken from the MH, WPR, or Cornish type is about twice twice the number of that in WL chickens. Also, the number of hybridizing fragments of different size found within one line was twice as high in the broiler (on average 16.0 bands per line) and MH lines (20.5 bands per line) than in the WL lines (10.0 bands per line). In studies with subregion-specific probes, all ev fragments detected contained the env (3') part of the viral genome. Only eight ev fragments, found in 7 animals of 2 lines, lacked the gag (5') part of the viral genome. Studies with the ev-1-specific flanking probe, pGd111, revealed that ev-1 is commonly present in the DNA of the WL chickens, but not within the DNA of the WPR chickens. The results suggest that use of the standard nomenclature for the ev genes based on restriction fragment length is not feasible within the WPR, MH, and Cornish lines because of the complexity of the ev gene patterns found within these lines. PMID- 1886839 TI - Selection for high and low threshold body weight at first egg in broiler strain females. 1. Direct response to selection and correlated effects on juvenile growth rate and age at first egg. AB - A selection program for high and low threshold body weight at first egg was carried out in a broiler line. Selection was on the basis of weight at first egg, following gradual release from feed restriction at a relatively advanced age. After six generations of selection, the lines differed by 862 g in the trait under selection. In addition, 6-wk body weight of high-line (HL) birds was 91 g greater, and age at first egg was 32 days greater than in low-line (LL) birds. When raised under an ad libitum feeding regimen from hatch, HL birds entered lay 20 days later than LL birds. When onset of lay was markedly delayed by maintaining feed restriction until 29 wk of age, body weight at first egg of HL birds was greater by 645 g than that of LL birds. Similarly, when birds of the two lines were subjected to forced molt and brought to a body weight well below that of initial body weight at first egg, and then allowed to gain weight and reenter lay, body weight difference at first egg of HL and LL birds following rehabilitation was similar to that found on original entry into lay. It is proposed that the results may most plausibly be explained as resulting from a primary effect of the selection procedure on the time required to first egg from onset of sexual competence, defined as onset of responsiveness to lay-inducing factors such as light. Alternative explanations involve effects of the selection procedure on threshold weight or threshold age requirements for sexual competence. PMID- 1886840 TI - Phenotypic, embryonic, and neonatal effects of a gene for sex-linked imperfect albinism (Sal-s) in chickens. AB - Gross phenotypic observations, histology, and tissue culture showed that the gene for sex-linked imperfect albinism that occurred at the University of Saskatchewan (Sal-s), allows a small amount of melanin pigment to be deposited in eyes and feathers. Melanin pigment accumulates in retinal pigment epithelial and cultured neural crest cells, but neural crest cells pigmenting the feathers transfer their pigment as it is produced, and this is seen as a constant amount of color in successive generations of feathers. Despite differences from early reports, it would appear that the phenotype produced by Sal-s is essentially the same as that produced by other Sal mutations. Albinos have a high incidence of lesions in the regions of the navel, the hocks, and the nares, similar to those associated with other hypomelanic mutations in the chicken. Yolk contents appear to be used more slowly by albinos late in incubation. The increased size of the yolk sacs probably contributes directly to producing the navel lesions and indirectly to variation in hatch weight. Albinos have small bursae of Fabricius, reduced hatchability, and early growth. PMID- 1886841 TI - Genetics of growth and reproduction in the turkey. 12. Results of long-term selection for increased 180-day egg production. AB - A line of turkeys selected 28 generations for increased 180-day egg production (E) was compared through regression analysis with the randombred control population (RBC1) from which it originated. The only curvilinear trends observed for RBC1 were for egg weight and 8-wk (both sexes) and 16-wk (males) BW. Linear declines in egg production and rate of lay through 84 and 180 days of lay, the number of clutches during the 180-day production period, effective days of egg production, and 16-wk (females) and 20-wk (both sexes) BW were observed for RBC1. The RBC1 turkeys had linear increases in the percentage of broody hens during the first 84 and 180 days of production, the average length of the broody period, and the total number of days lost to broodiness during the 180-day period. When expressed as a deviation from RBC1, positive quadratic curvilinear changes were observed for E turkeys for number of clutches and broody periods, and days lost to broodiness during the first 180 days of production. Percentage hatch of fertile eggs at 8 and 12 wk of production also exhibited a positive quadratic change with generation. Linear increases in egg production, rate of lay, clutch length (average and maximum), number of effective days of production, and percentage hatch of fertile eggs 12 wk into production were observed for E turkeys. There were linear declines in number of days from photostimulation to the production of first egg, number of clutches, and number, average length, and days lost to broodiness for E line turkeys.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1886842 TI - Decreased Salmonella colonization in turkey poults inoculated with anaerobic cecal microflora and provided dietary lactose. AB - The effect of intracloacal inoculation with anerobic cultures of cecal microflora and addition of lactose to the feed on Salmonella senftenberg cecal colonization was evaluated in turkey poults. One-day-old poults were divided into four groups and provided 1) no anaerobic cultures, no lactose (control), 2) anaerobic cultures, 3) 5% lactose in the feed, or 4) anaerobic cultures and lactose. All groups were challenged orally with 10(6) S. senftenberg at 3 days of age. Salmonella senftenberg growth in the cecal contents was significantly decreased (P less than .05) at 10 and 30 days of age in both trials and at 20 days of age in Trial 1 in each of the three treatment groups as compared with the controls. On Day 30, the number of poults that were positive for Salmonella cecal culture was significantly decreased (P less than .01) in each of the treatment groups compared with the controls. Protection against Salmonella colonization was similar in the treatment groups inoculated with anaerobic cultures or provided dietary lactose. Combined treatment with anaerobic cultures of cecal microflora and provision of dietary lactose resulted in a level of protection against colonization equal to or higher than did either of the two treatments administered separately. PMID- 1886843 TI - The individual and combined toxicity of kojic acid and aflatoxin in broiler chickens. AB - The individual and combined effects of kojic acid and aflatoxin were studied in male broiler chicks (Peterson x Hubbard). The experiment had a two by two factorial arrangement of treatments with dietary treatments of 0 and 2,500 mg kojic acid/kg feed and 0 and 2.5 mg aflatoxin/kg feed. The broilers were obtained at 1 day of age and housed in electrically heated batteries with feed and water available for ad libitum intake until they reached 3 wk of age. The toxicity of kojic acid was characterized by significant (P less than .05) reductions in body weight, the relative weight of the bursa of Fabricius, serum cholesterol concentration, and serum alkaline phosphatase activity, and by significant (P less than .05) increases in the relative weight of the pancreas, proventriculus, and gizzard, and serum concentrations of uric acid and triglycerides. Aflatoxicosis was characterized by significant (P less than .05) reductions in body weight, serum concentrations of total protein, albumin, cholesterol, and inorganic phosphorus, serum glutamic oxalacetic transaminase activity, and mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration. Significant (P less than .05) increases in the relative weight of the liver, kidney, spleen, pancreas, proventriculus, and heart, and the serum pyruvic transaminase activity were also caused by aflatoxin alone. The only significant (P less than .05) interaction between kojic acid and aflatoxin, which can best be described as antagonistic, was seen through an increase in mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration. These data indicate that kojic acid is not an aflatoxin synergist at the levels used in the present study. PMID- 1886844 TI - Differential resistance to Staphylococcus aureus challenge in two related lines of chickens. AB - Trials were conducted to determine whether differential resistance to challenge with Staphylococcus aureus was characteristic of two related lines of New Hampshire chickens differing genetically in size of the bursa of Fabricius. Neonatal small bursa line (SBL) chicks were superior to the unselected Lester J. Dreesen (LJD) line in five of six trials employing intracardiac challenge (chi 2 = 6.3, .05 greater than P greater than .01). Older (7 to 12 wk) SBL chicks, challenged intravenously, had superior resistance than Line LJD chicks in three of four trials where a direct comparison was possible. The mortality rate in Line SBL was 34% in all trials compared with a 54% mortality rate (chi 2 = 11.7, P less than .001) in Line LJD. Moreover, the development of morbidity was more rapid in Line LJD. It is suggested that these lines can be of use in investigations of the nature of resistance to staphylococcal disease. PMID- 1886845 TI - Effect of surgical and chemical in ovo bursectomy on lymphocyte density scores and histological evaluations of primary and secondary lymphoid organs in hypertensive and hypotensive turkeys. AB - The effects of surgical and chemical in ovo bursectomy on the histology of primary and secondary lymphoid organs were studied in hypertensive and hypotensive lines of turkeys. The effects of bursectomy were measured by determining the presence of lymphatic nodules and the presence of lymphocytes in secondary lymphoid organs: spleen, cecal tonsil, Meckel's diverticulum, and Peyer's patches; as well as in the thymus and bursa of Fabricius. No treatment effect on splenic nodule formation occurred, but a significantly lower lymphocyte density score was present in the surgically bursectomized group. Both nodule formation and lymphocyte density scores for the cecal tonsil and Peyer's patches were significantly reduced in the surgically bursectomized and testosterone treated groups as compared with the control and sham groups. The most consistent depression in lymphatic scores in both the surgically and chemically bursectomized groups occurred in the Peyer's patches followed by cecal tonsils and Meckel's diverticulum. As expected, there were no differences in thymocyte density scores. There was no consistent effect on lymphatic scores due to blood pressure selection; however, the hypertensive line showed significantly lower scores than the hypotensive line in the bursa, cecal tonsils, and Peyer's patches. No differences between the sexes were noted in any organ. PMID- 1886846 TI - Some effects of dietary aluminum and silicon on broiler chickens. AB - Experiments were conducted to determine whether dietary silicon will reduce the toxic effects of dietary aluminum on broiler chickens. The parameters measured were weight gain, feed efficiency, percentage bone ash, tibial dyschondroplasia, and the retention of calcium, phosphorus, and phytin phosphorus. Experiments 1 and 2 were conducted with casein and gelatin-based purified diets and Experiments 3 and 4 with corn and soybean meal-based practical diets. All experiments used day-old broiler cockerels and lasted 16 days. Aluminum significantly reduced weight gain, feed efficiency, and percentage bone ash in all four experiments. Aluminum supplementation reduced the incidence and severity of tibial dyschondroplasia, but this effect was associated with a reduction in weight gain. Increasing dietary aluminum reduced the retention of phosphorus and phytin phosphorus. Silicon did not alleviate the effects of aluminum toxicity on any of the parameters measured but did independently increase growth rate in Experiments 1 and 2, Supplementary dietary silicon does not appear to reduce aluminum toxicity in broiler chickens. Aluminum appears to exert its toxic effect on chickens by reducing the retention of phosphorus and phytin phosphorus. PMID- 1886847 TI - Influence of dietary flaxseed oil on the performance, muscle protein deposition, and fatty acid composition of broiler chicks. AB - Experiments were conducted to assess the effect of feeding flaxseed oil on the performance, muscle protein deposition, and fatty acid composition of broiler chicks. Four levels of dietary flaxseed oil were fed in combination with animal tallow to give a total of 6% added fat in the diets. The diets were isonitrogenous and isocaloric. Mortality, weight gain, feed consumption, and feed efficiency were not significantly different among treatments. Dietary treatments had no significant effects on the relative weights of the Extensor digitorum communis and Sartorius muscles nor on their protein or lipid contents. Feeding flaxseed oil resulted in increased accumulation of omega 3 fatty acids in skeletal muscle lipids. Increased amounts of desaturation and elongation products (C20:3, C20:5, C22:5, and C22:6) of alpha-linolenate (C18:3 omega 3) were observed in the Sartorius muscle lipids of chicks fed flaxseed oil. Amounts of these omega 3 fatty acids increased with duration of feeding. The amounts of omega 6 fatty acids (C20:2, C20:3, C20:4) were significantly depressed in muscle lipids after 21 days of feeding flaxseed oil. The effects of flaxseed oil on tissue amounts of individual saturated fatty acids were minimal, but amounts of monounsaturated fatty acids, especially C18:1, were depressed. PMID- 1886848 TI - Comparison of different anticoccidials on processing characteristics and parts yield of broiler chickens. AB - Broilers were grown to 42 days of age on diets supplemented with salinomycin (60 mg/kg), monensin (99 mg/kg), or halofuginone (3 mg/kg) and continued on unmedicated diets to 49 days of age. There were no significant (P greater than .05) differences among anticoccidials in final body weight, feed conversion, or mortality rates. Samples of birds were processed for dressing percentage and parts yield. Both males and females fed salinomycin had significantly higher breast meat yield as a percentage of postchill weight than those fed halofuginone but not those fed monensin; differences were not significant for breast meat yield of males or females fed monensin or halofuginone. Males fed halofuginone had significantly heavier leg quarters than those fed salinomycin but not those fed monensin. Females fed salinomycin had significantly higher water uptake during chill than those fed monensin or halofuginone. Results of the present study indicate that the anticoccidial used in growing broilers may influence some carcass yield parameters. PMID- 1886849 TI - Research note: incidence, number, and serotypes of Salmonella on frozen broiler chickens at retail. AB - Two similar trials were conducted to evaluate broiler carcasses at retail for incidence, number, and serotypes of salmonellae. Twelve frozen carcasses were purchased from each of three retail outlets on two sampling days. Two of the brands purchased were produced and processed conventionally, but the third brand was produced and processed under organic conditions. The frozen carcasses were tempered to 4.4 C prior to microbiological sampling. All carcasses were sampled using a mechanical shaker and 100 mL of sterile water. Recovered rinse fluid was evaluated for levels of salmonellae using a three-tube most probable number technique. All recovered Salmonella isolates were serotyped using the Kauffmann White scheme. Incidence rates across the three brands ranged from 17 to 50%, with most probable number of salmonellae per 100 mL of recovered rinse fluid ranging from 5 to 34 organisms. Serotypes recovered include Salmonella typhimurium, Salmonella paratyphi, and Salmonella arizonae. PMID- 1886850 TI - Research note: the in vitro responses of vaginal tissue and chicken spermatozoa to glycerol. AB - The fertilizing ability of glycerolized spermatozoa is apparently lost due to reactions between glycerol, spermatozoa, and vaginal tissue. Two experiments were conducted to determine the feasibility of using in vitro cultures to quantitatively assess these reactions. In the first experiment, vaginal slices alone, unglycerolized semen, and vaginal slices plus semen, all in a phosphate buffered saline were studied. The media were separated into 14 fractions using HPLC and the absorbance of each fraction was measured at 0 and 1 h of incubation. In a second experiment the changes in absorbance of these fractions were examined for unglycerolized and glycerolized semen in vaginal cultures. When unglycerolized semen was added to the vaginal cultures, Fraction 55 appeared in significantly greater absorbance than in vaginal tissue or semen alone. The opposite occurred for Fraction 57, which decreased in absorbance after 1 h of incubation in semen-vaginal culture. Fraction 57 was increased in absorbance in the presence of glycerol in the semen-vaginal culture. Glycerol appears to block the appearance of Fraction 55 in the normal semen-vaginal reaction. This reaction may be responsible for the deleterious effects of glycerol on spermatozoal survival in vivo. PMID- 1886851 TI - Research note: fumaric acid enhances performance of broiler chickens. AB - Two studies were conducted to examine the effects of dietary inclusion of fumaric acid on performance and carcass composition of broiler chickens. Fumaric acid was added to nutritionally complete diets at levels of 0, .125, .25, and .5% and fed from 1 to 49 days under simulated commercial conditions. In one trial, samples of birds were processed to determine dressing percentage and abdominal fat content. In the first trial (mixed sex broilers), the addition of .125% fumaric acid significantly (P less than .05) improved 49-day body weight of females and average weight gain of both sexes with no effect on feed utilization. Feed consumption was significantly increased when diets contained .125 or .50% fumaric acid. In the second trial (male broilers), 49-day body weight was significantly (P less than .05) improved by the addition of .125 and .25% fumaric acid. There were no significant differences in feed consumption; feed utilization was improved by the addition of all levels of fumaric acid. Dietary fumaric acid had no adverse effects on dressing percentage, abdominal fat content, or mortality rate. PMID- 1886852 TI - Research note: use of consecutive carcass rinses and a most probable number procedure to estimate salmonellae contamination of inoculated broilers. AB - Two similar trials were conducted to evaluate the accuracy of the whole carcass rinse technique in combination with a most probable number (MPN) procedure for estimating the number of salmonellae on postchill broilers. Birds were reared in litter-floored pens and inoculated with Salmonella typhimurium (10(8) cfu/mL) on Days 2, 7, and 14. In each of the two trials six carcasses were consecutively rinsed four times. Each carcass was rinsed with 100 mL of sterile water in sterile plastic bags using an automated shaking device. Salmonellae were enumerated using a three-tube MPN procedure in selenite cystine broth. There were no statistical differences in log10 MPN salmonellae per milliliter of recovered rinse fluid due to trial or consecutive rinse. In several cases salmonellae were not recovered in the initial rinse but were recovered from consecutive rinses of the same carcass. A large amount of variation in MPN levels of salmonellae among individual carcasses occurred within each consecutive rinse. The data suggested that only a percentage of the total salmonellae present on a postchill carcass were recovered with each consecutive rinse, and the organisms were firmly attached prior to processing. PMID- 1886853 TI - Genetic resistance to a Marek's disease transplantable tumor cell line in chicken lines selected for different immunological characters. AB - The tumor incidence and mortality of Marek's disease (MD) were determined for 471 progeny from four pairs of lines two-way selected for different immunological characters: graft versus host reaction (GVHR) competence, IgG levels, antibody response to rabbit serum albumin (RSA), and anaphylactic shock to BSA. All chicks were inoculated at 1 wk of age with 1 to 2 x 10(6) viable cells of a MD lymphoblastoid cell line, MDCC-MSB1-41C (41 C). Tumor incidence differed significantly between the high (H) and low (L) lines of each GVHR-, IgG-, RSA-, or BSA-selected group. There were also significant differences in mortality rates between H and L lines of all selected groups. The IgG-H, BSA-H, and RSA-H lines were more resistant than their respective L lines. The H line of the GVHR selected lines was more susceptible than the L line. Tumor regression could be detected only in the IgG- and RSA-selected lines. No definite correlation could be found between genetic resistance to 41C and genetic resistance to MD virus. PMID- 1886854 TI - Comparison of Henderson's Method I and restricted maximum likelihood estimation of genetic parameters of reproductive traits. AB - Genetic parameters of simulated reproductive traits were estimated with Henderson's Method I or restricted maximum likelihood (REML). Each of the 25 samples consisted of 2,667 birds from 50 sires. When reproductive traits were measured on all birds, the means of both sets of estimates were equal to the true value; however, precision was higher with REML. When they were only measured on the 60 (20%) heaviest birds, Henderson's Method I was severely biased by selection (up to 40% for estimates of heritability of reproductive traits and up to 45% for estimates of genetic correlation between reproductive traits and body weight). This bias, as well as the variance of estimates, increased with selection rate and absolute value of genetic correlation between body weight and reproductive traits (or another criterion of selection). Conversely, REML was not biased by selection. It should therefore be preferred when sequential selection occurs. PMID- 1886855 TI - Use of the sex-linked barring (B) gene for chick sexing on an eumelanotic columbian background. AB - A study was carried out to see whether the near-black down of an eumelanotic columbian phenotype (eWh/eWh, Co/Co, Ml/Ml) could be used in color sexing crosses as a background for the expression of the sex-linked barring (B) gene. Barred (B) and nonbarred (b+) alleles were accurately identified on a heavily eumelanotic columbian phenotype, which provides a brown-faced black down for the B-induced white head spot. Color sexing was possible due to the association between barred males (B/b+) and white head spot. Average accuracy obtained was 97%. Sexing was not possible in the presence of heterozygous Ml/ml+. PMID- 1886856 TI - Effects of selection for growth and selection diet on eggshell quality and embryonic development in Japanese quail. AB - Decreased hatchability in Japanese quail following selection for growth and relative improvements in hatchability following selection during goitrogen treatment were investigated. An unselected quail line (Line C) and lines selected for high 4-wk body weight while being fed diets containing either 20% CP and .2% thiouracil (TU) (Line T), or 28% CP and no TU (Lines P and H-CD) were used. Egg weight loss between 0 and 4, and 0 and 14 days of incubation, hatchability, and developmental stage of embryonic mortalities were determined in Experiment 1. Length of the incubation period, and percentages of body water and dry body weight were determined for 10- and 14-day embryos and 18-day-old chicks in Experiment 2. Eggshell quality was determined in Experiment 3. Hatchability was lower in selected than in unselected quail due to increased early and late embryonic mortality. Egg weight loss during incubation was greater in Line P than in Line C eggs. Weight loss, measured across lines, was lower in eggs that hatched than in those in which embryos died early. Percentage body water was higher in Line C than in Lines P and T at 14 and 18 days of incubation; however, percentage body water in Line T was lower than Line P at 14 days. Percentage of dry body weight was greater in Lines P and T than in Line C at 14 and 18 days. Eggshell thickness was greater in Line H-CD when compared with Line C. Increases in eggshell permeability occurring during selection for growth were associated with increased embryonic mortality and decreased hatchability.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1886857 TI - Effect of ahemeral light:dark cycles on egg production in early photostimulated brown-egg pullets. AB - A laying trial was conducted to determine the effect of an ahemeral lighting program on early photostimulated brown-egg pullets (DeKalb Sex-Sal). All birds received 24 h of light/day (24L:0D) to 3 days of age followed by 8 h of light (8L:16D) to 8 wk of age. From 8 to 16 wk the birds received 10 h of light daily. At 16 wk, the control group (CON) received 11 h of light and 13 h of darkness (11L:13D) followed by a weekly 1-h increase in photoperiod to 14L:10D at 19 wk, which was maintained for the duration of the trial (59 wk of age). Birds on the ahemeral (AHM) schedule were exposed to a 26-h schedule of 11L:15D at 16 wk with a weekly 1-h increase in the photoperiod to 14L:12D at 19 wk. The AHM schedule (14L:12D) was maintained from Weeks 19 to 30 at which time birds were returned to a 24-h cycle of 14L:10D and kept on this schedule for the remainder of the trial. Egg weight was significantly increased by the AHM treatment for 27 to 30 wk; however, there was no cumulative (Weeks 19 to 59) effect on egg weight. Percentages of eggs per hen per day (%HDP) were significantly reduced by the AHM treatment for the periods 23 to 26 wk and 31 to 34 wk. This reduction caused a significant cumulative effect on %HDP (68.9 for CON versus 66.2 for AHM).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1886858 TI - Growth and performance of broiler breeders fed bacitracin methylene disalicylate and zinc bacitracin. AB - Day-old Cobb broiler breeder pullets were randomly allotted into 20 floor pens where they were brooded and reared to 23 wk of age. Eight pens received a control diet containing no growth promotant. The other 12 were fed 55 mg of bacitracin methylene disalicylate/kg of diet. Males were reared separately on the control diet. Pullets were full-fed for the first 8 wk of life, then placed on a skip-a day program with breeder-recommended feed allocations. At 23 wk of age bird numbers were reduced to 26 females per pen, three males added, and diets changed to the layer regimen. Levels of 0, 27.5, 55, or 110 mg/kg of zinc bacitracin were each assigned to five pens with factorial attention to growing treatment. Layer treatments were continued for 280 days. No significant differences were associated with the feeding of bacitracin methylene disalicylate among body weight or mortality data summarized at 8 and 23 wk. Eight-week feed efficiency was also not affected. In the laying phase, 110 mg/kg of zinc bacitracin significantly improved egg production and fertility over the unsupplemented controls. Hatch of fertile eggs, overall hatchability, and the number of chicks per pen were all significantly improved by 27.5 mg/kg of zinc bacitracin. Higher drug levels supported no additional improvement. Feed efficiency, mortality rate, and final body weight were not significantly influenced by any level of supplementation. No effect of grower treatment upon subsequent layer performance was noted. PMID- 1886859 TI - Behavioral correlates of male mating success in a multisire flock as determined by DNA fingerprinting. AB - The fertility of an individual rooster within a multi-sire flock may be influenced by a number of behavioral considerations, including frequency and timing of matings and the male's position in the social dominance hierarchy. The relationship between behavior and fertility has proven difficult to assess, however, because there are a limited number of heritable morphological traits that can be used to determine paternity. The objectives of the present study were to use DNA fingerprinting to determine paternity in domestic fowl and to assess some behavioral and physiological correlates of mating success. Sixty day-old chicks from each of two commercial breeds, DeKalb White Leghorn (L) and Warren Color-Sexed (W), were reared in either same-breed or mixed-breed groups. At 43 wk of age, all females and six randomly selected males were mixed into one large pen. Male aggressive and mating behaviors were recorded over a 4-mo period. Fertility of individual sires was determined by DNA fingerprinting and pedigree analysis of chicks. Dominance rank and the frequencies of both completed matings and mating attempts were positively correlated with fertility (P less than .01). In addition, wing flapping was correlated with both dominance (P less than .001) and fertility (P less than .05). There was no correlation between fertility and plasma testosterone. There were breed effects on dominance status, with W dominating L. Multiple paternity was demonstrated in 4 out of 10 families by DNA fingerprinting. The present study is the first one to demonstrate a correlation between dominance and fertility in a flock containing several males of the same breed and morphology. PMID- 1886860 TI - Effects of air humidity during incubation and age after hatch on heat tolerance of neonatal male and female chicks. AB - Effects of incubation 45 versus 55% relative humidity (RH) and early versus late hatching time on heat tolerance of neonatal male and female chicks were studied. Chicks were exposed for 48 h to temperatures of 35 (Experiment 1), 37 (Experiment 2), or 39 C (Experiment 3). Chicks that hatched from eggs incubated at 45% RH were lighter at hatch than chicks that hatched from eggs incubated at 55% RH. Chicks that hatched from eggs incubated at 55% RH lost more body weight and water during heat exposure than those that hatched from eggs incubated at 45% RH. Body weight and water loss during heat exposure of chicks that hatched early and late was similar. However, chicks that hatched late maintained their initial heat production and respiratory quotient better during heat exposure than chicks that hatched early. Body weight and water loss of male and female chicks was similar. At 37 and 39 C, heat production of chicks fell to lower values during the 2nd day of exposure compared with the 1st day. It was concluded that chicks that hatched late, i.e., with a short holding period in the hatcher, and coming from eggs incubated at 45% RH had increased heat tolerance in comparison with the other chicks. PMID- 1886861 TI - Effects of incubation humidity and hatching time on heat tolerance of neonatal chicks: growth performance after heat exposure. AB - Three experiments were performed with 300 neonatal Hisex Brown layer chicks in each. The chicks hatched from eggs incubated at a relative humidity (RH) of 55 or 45%. Within each RH group, two groups were separated based on hatching time (early and late hatch groups). After hatch, 60 chicks served as controls. The other chicks were exposed to 35, 37, or 39 C for 48 h. After exposure, a 4-wk experimental growing period started at Day 2 of age. Chicks exposed to the experimental temperature regimens for 2 days had lower body weights at the end of exposure and grew less than controls during the 1st wk afterwards. At Day 2 of age, chicks hatched from eggs incubated at 45% RH had higher body weights than chicks hatched from eggs incubated at 55% RH. These chicks also had higher body weight gain in the 1st and 2nd wk following exposure to 39 C than chicks hatched from eggs incubated at 55% RH. Chicks hatching late were heavier at Day 2 than early-hatching ones, but body weight gain was similar. Chicks exposed to the experimental temperature regimens had lower rectal temperatures than controls at the end of the 1st and 2nd wk. Incubation RH, hatching time, and sex did not affect feed intake, feed conversion, or rectal temperature. After exposure to 39 C, fewer chicks that had hatched from eggs incubated at low RH died compared with chicks that had hatched from the 55% RH group. Early-hatching chicks had a significantly higher risk of dying than late-hatching ones. PMID- 1886862 TI - Peanut agglutinin as a marker of maturation and activation of chicken thymic derived lymphocytes. AB - In mammals peanut agglutinin (PNA) is used for separation of lymphocytes into immature and mature T-cells. Lymphocytes that bind PNA are young and functionally immature, but the cells that do not bind PNA are considered mature. No conclusive information was published on PNA as a marker of lymphocytes maturation in chickens. The present results showed that T-lymphocytes that do not bind PNA (PNA ) responded significantly higher to Concanavalin A (Con-A) stimulation than PNA+ ones. During Con-A activation, a PNA receptor was revealed. Double staining of Con-A cultured lymphocytes revealed the presence of both I-associated antigen and PNA. Therefore, the PNA receptor, on chicken T-lymphocytes, was not indicative always of immaturity. During maturation, the receptor was covered and the cells were PNA-, but subsequent proliferation reverted PNA- cells to PNA+ cells. PMID- 1886863 TI - Modulation of chicken plaque-forming cells by serotonin and dopamine. AB - Serotonin (5-hydroxytryptamine, 5-HT) and dopamine (DA) are endogenous components of the central nervous and endocrine systems of the chicken. To determine the effects of these monoamines on antibody-mediated immunity. New Hampshire chickens of Line UNH 105 were injected intravenously with 5-HT (100 micrograms/kg of body weight) and DA (1 mg/kg of body weight). One milliliter of a 5% SRBC suspension was injected intravenously 30 min later. Both IgM and IgG splenic plaque-forming cells were assayed 5 days after antigen injection. For in vitro studies, spleen lymphocytes from SRBC-primed chicks were incubated with DA and 5-HT followed by quantitation of IgM and IgG plaque-forming cells. The in vivo incubation of splenic lymphocytes with specific antagonists was used to ascertain the presence of monoamine receptors on lymphocytes. The 5-HT significantly enhanced IgM plaque forming cells compared with controls following in vivo [550 +/- 85 (SE) cells/10(6) splenic lymphocytes versus 359 +/- 44] but not in vitro exposure. The IgG plaque-forming cells were not affected by 5-HT. The DA significantly suppressed IgM plaque-forming cells responses following in vivo (284 +/- 46 versus 499 +/- 66) and in vitro (254 +/- 57 versus 451 +/- 51) exposure. Significant suppression of IgG plaque-forming cells was found in vivo (287 +/- 40 versus 462 +/- 75) and in vitro (153 +/- 36 versus 371 +/- 81) following treatment. Specific DA antagonists, apomorphine and metoclopramide, did not alleviate the in vitro suppressive effect of DA. PMID- 1886864 TI - Prediction of the apparent metabolizable energy content of fats fed to broiler chickens. AB - Soybean oil and tallow acid oil were blended in the ratio 75:25, 50:50, and 25:75 to give 3 blends (A, B, and C) of increasing free fatty acid (FFA) content but decreasing ratio of unsaturated to saturated fatty acids (U:S). Tallow and soybean acid oil were blended in similar proportions to give three blends (D, E, and F) of increasing FFA content and increasing U:S ratio. The six fats were incorporated into a basal diet at rates of 40, 80, and 120 g/kg. Experimental diets were evaluated for apparent available fat (AAF) with broilers aged 1.5 and 7.5 wk of age. The AAF of fats was calculated from extrapolation of the regression of AAF of diets to rate of inclusion of fats. The AME of fats was determined as the product of AAF and gross energy. Increasing FFA content but reducing U:S ratio lowered the AME giving 31.1, 28.7, and 21.7 MJ/kg (1 MJ = .239 Mcal) and 33.2, 31.5, and 28.4 MJ/kg, respectively, for A, B, and C for young and old birds. Corresponding data for D, E, and F (increasing FFA content and U:S ratio) were 27.7, 28.0, and 29.4 MJ/kg and 31.8, 32.9, and 33.3 MJ/kg, respectively, for young and old birds. Data generated, together with results from previous reports, were subject to regression analysis. The AME of fats could be predicted from knowledge of U:S ratio and FFA content with equations accounting for .816 and .925 of the variation in AME values for young and old birds, respectively. PMID- 1886865 TI - The effect of minimizing amino acid excesses in broiler diets. AB - A series of experiments were conducted to evaluate the performance of 7- to 21 day-old broilers fed diets in which excesses of essential amino acids (EAA) were minimized. A 23% protein diet in which all EAA except TSAA were in excess was reduced in protein in a stepwise manner, keeping the corn; soybean meal ratio constant, to the point where all EAA were at minimum requirement level based on the 1984 National Research Council (NRC) requirements. Crystalline EAA supplemented those EAA that became deficient as dietary protein was reduced. Other test diets included one containing an additional 10% of the particular EAA in question and one with nonessential amino acids (NEAA) added to make the low protein diet isonitrogenous with the 23% control. Performance of birds fed the low-protein test diets was not significantly different from that of the control birds. All EAA appeared to be adequate at levels recommended by the NRC in 1984 except Trp, which required .25% for optimal performance. A growth response was observed when Gly was used as the NEAA source; however, no response was noted when mixtures of NEAA were used as the NEAA source, suggesting that Gly may have been limiting in these earlier treatments. Total carcass protein of birds fed the low-protein test diets in which all EAA were minimized was equal to that of the control birds. In a final experiment utilizing the EAA-balanced, low-protein diet, dietary energy was allowed to vary by 15%. The EAA intake was constant, indicating that birds were eating to satisfy EAA requirements rather than energy requirements. Increased carcass fat deposition paralleled dietary energy increases. PMID- 1886866 TI - Effect of dietary protein level and length of feeding on performance and abdominal fat content of broiler chickens. AB - Dietary CP levels influence carcass fat content of chickens but the length of time necessary to feed higher levels in order to increase carcass fat is not known. Studies were conducted to evaluate the effects of length of feeding of different levels of dietary CP on broiler performance and abdominal fat deposition. All diets were calculated to be isocaloric at 3,200 kcal ME/kg. Broilers fed 23% CP for 0 to 21 days, 20% CP for 21 to 42 days, and 18% CP for 42 to 49 or 42 to 56 days served as the control group in each of two trials. In the first trial, broilers were fed constant levels of CP from day-old to market age with CP levels ranging from 15 to 27% (amino acids adjusted in proportion to CP level). Other broilers were fed 23% CP for 0 to 21 days and then fed either 15, 17, 19, or 21% CP to market age. In the second trial, broilers were fed constant levels of CP (18, 20, or 23%) from day-old to market age. Feeding CP levels lower than those fed the control group had a more pronounced effect on males than on females, with the primary effects being reduced body weight, poorer feed utilization, and increased carcass fat content. Feeding CP levels higher than those fed the control group generally did not increase final body weight but generally improved feed utilization and decreased carcass fat content. The economics of improved feed utilization and reduced carcass fat must be considered in determining dietary CP levels to use at different ages for growing broilers. PMID- 1886867 TI - Increased skin tearing in broilers and reduced collagen synthesis in skin in vivo and in vitro in response to the coccidiostat halofuginone. AB - In vivo and in vitro experiments were conducted in an effort to elucidate the mechanism of suppression by halofuginone of skin strength in broilers. In the in vivo study, halofuginone was included at concentrations of 0, 1.5, 3, and 6 mg/kg of diet, corresponding to 0, 50, 100, and 200%, respectively, of the amount recommended for use as a coccidiostat. Each dietary treatment was given to 260 female broiler day-old chickens. Skin tearing was evaluated at the processing plant. Skin collagen and Kjeldahl-nitrogen were determined chemically. At the age of 7 wk, BW and feed efficiency were affected only in birds consuming the diet containing the highest concentration of the drug. Skin tearing increased but skin collagen concentration decreased in a dose-dependent manner. Fibroblasts were obtained by collagenase digestion from chicken skin and cultured. The cultured cells were incubated with various concentrations of halofuginone, monensin, and nicarbazin, and [3H]proline incorporation was evaluated in collagenase-digestible (representing mostly collagen) and nondigestible proteins exported by the cells into the medium. Halofuginone, at a concentration as low as 10(-11) M, inhibited incorporation of [3H]proline into collagenase-digestible proteins, but did not affect incorporation of [3H]proline into collagenase-nondigestible proteins. Even at concentrations as high as 10(-9) M, neither monensin nor nicarbazin affected collagenase-digestible proteins. The in vitro results suggest that halofuginone specifically inhibits collagen synthesis by skin fibroblasts. Results of both in vivo and in vitro trials suggest that the increase of skin tearing during processing, induced by halofuginone, is caused by direct suppression of skin collagen synthesis. PMID- 1886868 TI - The effects of various dietary phosphorus levels on the circadian patterns of plasma 1,25-dihydroxycholecalciferol, total calcium, ionized calcium, and phosphorus in laying hens. AB - Six hundred and sixty 75-wk-old Hy-line W36 hens were allocated to one of three dietary levels of total phosphorus, .30, .60, or .90%. Birds were fed the diets for 3 days following which blood samples were collected at six different times, 2, 6, 10, 14, 18, and 22 h postoviposition (POP), and analyzed for 1,25 dihydroxycholecalciferol [1,25-(OH)2 D3], total calcium (TCa), ionized calcium (Ca++), percentage Ca++ to TCa (%Ca++/TCa), and phosphorus (P). Plasma TCa and P significantly (P less than .001 and .025, respectively) peaked at 10 to 14 h POP. The Ca++ and %Ca++/TCa significantly (P less than .001) decreased during eggshell formation and following completion of the shell (22 h POP) levels returned to resting concentrations. Plasma 1,25-(OH)2D3 results confirmed the existence and time of a circadian rhythm in laying hens. Peak concentrations of the metabolite occurred at 10 to 14 h POP, which resulted in a quadratic relationship (P less than .001). Plasma P decreased with decreasing dietary P and plasma 1,25-(OH)2D3 increased (P less than .025). Feeding low dietary P significantly (P less than .001) increased Ca++ and %Ca++/TCa. Results of feeding various levels of dietary P to laying hens indicate that low P stimulates an increase in plasma 1,25 (OH)2D3 as well as Ca++ and %Ca++/TCa, but high P actually suppressed this response. PMID- 1886869 TI - The effect of pelleting, salt, and pentosanase on the viscosity of intestinal contents and the performance of broilers fed rye. AB - An experiment was conducted to determine the impact of pelleting of rye, dietary salt (.39 and .57%), and crude pentosanase supplementation (0 and .2%) on the viscosity of intestinal contents and the concomitant performance of broiler chicks fed rye-based diets. Each treatment was replicated six times with six birds per replicate. Test diets were fed from 1 day to 3 wk of age, at which time body weight, feed intake, intestinal viscosity, and molecular weight distribution of carbohydrate complexes were determined in fore and hind gut sections. Enzyme supplementation in all treatment combinations significantly increased weight gains and feed conversion efficiency (FCE). Pelleting and salt did not influence weight gain or FCE, although feed intake was increased through the addition of salt. The viscosity of fore and hind gut contents was significantly reduced with pentosanase supplementation, whereas the effects of salt or pelleting were not as clearly defined. Weight gain and FCE correlated with fore but not hind gut viscosity. The viscosity of gut samples was found to be best described by the concentration of carbohydrate complexes with an average molecular weight greater than 500,000 Da. Pentosanase treatment reduced lumenal concentration of these complexes, thereby reducing viscosity and stimulating improvements in growth and FCE. PMID- 1886870 TI - Plasma, follicular, and uterine levels of prostaglandins in chickens laying soft shelled and shell-less eggs. AB - Not all eggs produced by chickens are laid at the expected time of oviposition. Some eggs are laid prematurely, which result in inadequate shells. These uncollectible eggs are referred to as soft-shelled (partial calcification) or shell-less (no calcification) eggs. Of all soft-shelled or shell-less eggs that were laid in the present study, 57% were expelled prematurely. To determine whether prostaglandins were correlated with the expulsion of soft-shelled or shell-less eggs, prostaglandin F2alpha (PGF2alpha), 13,14-dihydro-15 keto prostaglandin F2alpha (PGFM), and 13-14-dihydro-15 keto prostaglandin E2 (PGEM) were measured in the peripheral plasma and follicular and uterine tissues of hens laying soft-shelled eggs and shell-less eggs. Controls were represented by hens laying hard-shelled eggs (normal calcification). Plasma concentrations of PGFM increased (P less than .01) upon the premature oviposition of soft-shelled eggs but not shell-less eggs. The source of the peripheral PGFM may have been the preovulatory follicle, because PGF2alpha levels were higher (P less than .07) in the soft-shelled or shell-less egg layers when compared with the controls. Plasma and tissue levels of PGEM did not differ between hens laying soft-shelled or shell-less eggs versus hard-shelled eggs. These results suggest that PGF2alpha and PGFM are involved in the premature oviposition of some chicken eggs. PMID- 1886871 TI - Performance of two male broiler breeder strains raised and maintained on various constant photoschedules. AB - The purpose of the present study was to examine the interaction of constant photoschedules and genetic background on performance of male broiler breeders. Day-old cockerels from two BW strains were placed on litter floors in light controlled chambers. Light treatments (LT) (60 lx) consisted of 2, 4, 8, 16, and 24 h light/day. At 9 wk of age, birds were individually caged and evaluated biweekly for semen production. Venous blood samples were collected at 16, 32, 48, and 64 wk of age. Data for testes weight, histology, and morphometry were obtained at 64 wk. Age at first semen production showed a cubic response in the levels of LT with earliest semen production from 4 and 8 h light (187.0 and 188.2 days, respectively). The BW was linear in the levels of LT within week; average BW was generally greater for birds on short LT than for birds on longer LT. Semen concentration was also linear in the levels of LT within week; increased semen concentration occurred with short LT. Changes in semen weight and spermatozoa count per ejaculate across the levels of LT differed for strain. A larger percentage of males produced semen in the less than or equal to 8 h LT than in the 16 or 24 h LT. Plasma testosterone was lower at 16 wk compared with later ages, and a positive linear relationship existed between testosterone level and hours of light. There was a cubic LT effect for testes weight per BW with larger values for less than or equal to 8 h LT compared with 16 or 24 h LT. PMID- 1886872 TI - Hypothalamic biogenic amine levels in broiler chicks showing advanced sexual maturation. AB - Parasagittal knife cuts through the lateral hypothalamic area of 2-wk-old male broiler chicks induced precocious testes development. Two experiments were performed to determine whether hypothalamic biogenic amine levels in these chicks were changed by lateral hypothalamic deafferentation. In Experiment 1, chicks responding to surgery with advanced sexual maturation had reduced levels of norepinephrine (NE), epinephrine (E), and homovanillic acid (HVA) in the anterior hypothalamus and elevated levels of dopamine (DA) and serotonin in the median eminence, compared with controls. In Experiment 2, NE and HVA were reduced in the anterior hypothalamus of nonresponders. Dopamine was reduced in the anterior hypothalamus of nonresponders and elevated in the median eminence of responders. Serotonin was found to be higher in the median eminence of nonresponders. The increased DA in the median eminence suggests an excitatory role for this neurotransmitter in gonadotropin release at puberty. PMID- 1886873 TI - The effects of busulfan on gonadal differentiation and development in Japanese quail (Coturnix coturnix japonica). AB - To determine the effects on gonadal differentiation and development, two concentrations of busulfan (1,4-butanediol dimethanesulfonate) were injected into the albumen of unincubated Japanese quail eggs, and the eggs were then incubated. Half of the hatchlings were killed at 3 days of age and the rest at 10 wk of age (4 wk past puberty). Hatchability of fertile eggs was lowest in those eggs injected with 420 micrograms of busulfan (19.6%), intermediate in the 210 micrograms group (54.7%), and highest in the sham-injected control group (73.3%). Gonads were examined histologically for germ cells and normal development. All 23 birds evaluated after injection with 210 micrograms of busulfan had histologically normal gonads. In the 420-micrograms group, six out of eight birds were abnormal. Three females and one male in this group had gonads lacking germ cells, and two males had testicles with a combination of normal seminiferous tubules and tubules lacking spermatogonia. PMID- 1886874 TI - Research note: beta-adrenergic agonist effects on liver and breast muscle protein synthesis in female chicks. AB - The effect of administration of clenbuterol, a beta-adrenergic agonist, on live weight gain and protein synthesis of liver and breast muscle was investigated in 32 White Leghorn chicks. Protein synthesis was measured by injection of [3H]phenylalanine in a wing vein using the flooding dose method. No significant changes in body weight gain were caused by dietary administration of the beta agonist at .25 mg/kg of diet from 3 to 6 wk of age, but fat retention in the liver and breast muscle was significantly reduced by the drug treatment. No stimulating effect on protein synthesis of the beta-agonist administration was found either in the breast muscle or in the liver. Protein synthesis in the breast muscle was unchanged whereas that in the liver was reduced significantly by feeding clenbuterol. PMID- 1886875 TI - Research note: ability of fenthion to increase gizzard erosion in broiler chicks. AB - Fenthion, an irreversible cholinesterase inhibitor, was used to study the role of the cholinergic system on the development of gizzard erosion. Fenthion increases the gizzard erosion score in a dose-dependent manner and this effect became significant at levels higher than .1 ppm (p less than .05). An inverse relationship between plasma cholinesterase activity and pesticide concentration was also observed at doses higher than 1 ppm (P less than .05). These results show the necessity to evaluate organophosphate pesticide levels during the selection of fish meals in poultry. PMID- 1886876 TI - [Use of ceramic materials in fixed prosthetic appliances]. AB - The development of the use of ceramic materials in stomatology has a long history. Their composition and processing should present in particular improve their strength and accuracy, while preserving excellent biocompatibility and satisfactory aesthetic appearance. Ceramic materials are increasingly used in fixed prosthetic appliances. The author summarizes hitherto assembled findings and outlines the trends of future development. PMID- 1886877 TI - [New radiodiagnostic methods from the aspects of the dental surgeon]. AB - Based on data in the literature and their own experience the authors summarize eleven imaging systems using ionizing energy and fifteen non-X-ray techniques from the aspect of the dental surgeon. Perspective methods include CT, DSA, xeroradiography, electrography in addition to classical X-ray techniques incl. intervention radiodiagnosis. As to non-X-ray techniques sonography (echography, USG), thermography and magnetic resonance prove useful. PMID- 1886878 TI - [Health problems in the Libyan Arab Peoples Socialist Republic]. AB - The author describes the social and medical situation in the Libyan Arab Peoples Socialist Djamahiriji. He presents an epidemialogical study of the prevalence of some malocclusions. From the results it is apparent that it is necessary to introduce systematic orthodontic care which does not exist so far in the country. PMID- 1886879 TI - [Compensation criteria of basal disease in the prevention and treatment of periodontal disease in patients with diabetes mellitus]. AB - The literature overview on the current diagnostic approaches in diabetology and on the subclassification of diabetes mellitus based on compensation criteria with regard to the prevalence and characteristics of periodontal disease. PMID- 1886880 TI - [Hand, foot and mouth disease]. AB - The authors described a case of viral stomatitis of the type of hand, foot and mouth disease with mucosal and skin manifestations in an adult with a significant rise of neutralizing antibodies against the Coxsackie B4 virus. PMID- 1886881 TI - Pancreatic cancer and the familial atypical multiple mole melanoma (FAMMM) syndrome. AB - The role of host factors in the etiology of pancreatic cancer has received a paucity of systematic investigation. Anecdotal reports and one population-based study have supported the concept that familial clustering of this disease exists. We have studied a kindred with a cancer-associated genodermatosis known as familial atypical multiple mole melanoma (FAMMM) syndrome (hereditary dysplastic nervus syndrome). Three key relatives have manifested pancreatic carcinoma. Since FAMMM may account for as much as 10% of the total malignant melanoma burden, its association with pancreatic cancer harbors important public health implications. Given the fact that the etiology of pancreatic cancer remains enigmatic, it is important to investigate all possible clues to its causality, including the potential role of host factors. PMID- 1886882 TI - Regulation of transforming growth factor-alpha mRNA expression in T3M4 human pancreatic carcinoma cells. AB - Cultured human pancreatic cancer cells produce transforming growth factor-alpha (TGF-alpha), a potent mitogenic polypeptide. In the present study, we investigated the regulation of TGF-alpha mRNA expression in T3M4 human pancreatic carcinoma cells. TGF-alpha mRNA levels were quantitated by densitometric analysis of autoradiographs obtained following hybridization of size-fractionated cytoplasmic RNA with 32P-labeled cRNA coding for human TGF-alpha. There was a twofold increase in TGF-alpha mRNA levels at 2 h following addition of either epidermal growth factor (EGF) or TGF-alpha. However, TGF-alpha mRNA levels declined to near basal levels by 10 h. At 2 h, one-half maximal stimulation of TGF-alpha mRNA levels occurred at 1 nM and maximal stimulation at 4 nM of either EGF or TGF-alpha. The transcriptional inhibitor actinomycin D (Act D) and the phorbol ester, 12-O-tetradecanoyl-phorbol-13-acetate (TPA), mimicked the actions of EGF and TGF-alpha. These findings indicate that the regulation of TGF-alpha mRNA expression in T3M4 cells is complex, and is mediated, in part, via the EGF receptor. PMID- 1886883 TI - Changes in gene expression during pancreatic regeneration: activation of c-myc and H-ras oncogenes in the rat pancreas. AB - Expression of the c-myc and H-ras oncogenes, and of several genes specifically expressed in adult rat pancreas was investigated by monitoring changes in corresponding mRNA concentrations, by dot-blot hybridization, during the early phase of regeneration following subtotal pancreatectomy. The oncogenes c-myc and H-ras were overexpressed after 12-24 and 48 h, respectively, then returned to basal levels. The concentrations of mRNAs encoding amylase, chymotrypsinogen B, and trypsinogen I decreased during the regeneration time. By contrast, proinsulin I mRNA concentration was increased at 12-48 h after surgical resection, and actin mRNA concentration was increased at 12-48 h after surgical resection, and actin mRNA concentration was increased at 12 h after subtotal pancreatectomy and remained elevated thereafter. We concluded that regeneration after subtotal pancreatectomy is accompanied by repression of certain genes that are expressed in differentiated pancreatic tissue, and that derepression of other genes may be necessary for starting and/or maintaining the process of pancreatic regeneration. PMID- 1886884 TI - cDNA sequence and deduced amino acid sequence of human preprocolipase. AB - Complementary DNA clones for human pancreatic colipase were identified in human pancreatic cDNA libraries by hybridization with a pool of synthetic oligonucleotides containing all possible coding sequences for amino acids 75 to 80 of the partial human colipase protein sequence (Sternby, et al. Biochim Biophys Acta 1984;784:75). Alignment of overlapping cDNA clones yielded an mRNA sequence of 504 nucleotides [not including the poly(A) tail] encoding a polypeptide of 112 amino acids. The prepeptide comprised 17 amino acids, with an amino-terminal cluster of charged residues followed by a hydrophobic core of 12 residues typical of leader sequences. The deduced human procolipase sequence comprised 95 residues, including a propeptide of 5 residues. It was in complete agreement with the partial sequence previously obtained by protein sequencing. Northern blot analysis revealed that the polyadenylated preprocolipase transcript had a length of approximately 680 nucleotides. PMID- 1886885 TI - Immunoreactive forms of pancreatic stone protein in six mammalian species. AB - Secretory forms of the pancreatic stone protein (PSP S, Mr 17, 500-22,000) have been purified from human pancreatic juice. PSP S are inhibitors of CaCO3 crystal growth. The presence of similar proteins in bovine, canine, monkey, porcine, and rat pancreatic secretion was investigated in terms of biological role and immunological relationship. Pancreatic proteins were analyzed by electrophoretic separation and by subsequent immunoblotting with a rabbit polyclonal antibody against human PSP. A single immunoreactive form was detected in dog, pig, and rat (Mr 17,000), and two distinct immunoreactive forms were observed in cow and monkey (Mr 15,000 and 17,000). Inhibition of CaCO3 crystal growth was demonstrated in dog and rat. Further kinetic studies of the inhibition process in the rat showed that PSP S binds to the crystal surface according to a Langmuir adsorption isotherm with a dissociation constant (Kd) of 1.5 x 10(-6) M. These results suggest that proteins homologous to human PSP S are present in other mammalian species and may act as stabilizers of Ca(2+)-supersaturated pancreatic juice. PMID- 1886886 TI - The acute pancreatotoxic effects of the plant nitrile 1-cyano-2-hydroxy-3-butene. AB - The effects of synthetic 1-cyano-2-hydroxy-3-butene (CHB), a racemic mixture of the (R)- and (S)-enantiomers, were studied in adult male rats. The compound given by gavage in olive oil at doses of 25-200 mg/kg causes toxic effects on the pancreas that resemble those seen when naturally occurring CHB is given to rats. At 6 h after dosing, pancreatic edema is seen with doses of 100 mg/kg and greater. The edema fluid had a high protein content, indicating a marked increase in macromolecular permeability of the pancreatic microcirculation. A loss of zymogen granules from the acinar cells and a lacy supranuclear vacuolation of the acinar cell cytoplasm was observed. At 4 h after dosing, pancreatic nonprotein thiols were depleted and rebounded at 24 h to three times control values. At 120 h nonprotein thiol levels decreased but were still elevated compared with control values. Glutathione-S-transferase activity in the pancreas had a similar pattern of change with initial reduction, followed by elevation at 24 h. In rats with pancreatic and biliary fistulas, intraduodenal CHB caused a transient early stimulation of pancreatic juice secretion followed by a return to control values in the case of the lower doses of CHB and depression of flows at larger doses. All doses of CHB caused a dose-related depression of protein concentration in pancreatic juice. Pancreatic juice flow was almost abolished at doses of 200 mg/kg. CHB caused a dose-dependent choleresis accompanied by a marked reduction in bile acid concentrations in bile.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1886887 TI - The cephalogastric phase of the pancreatic response to food in the dog. AB - We studied post-meal pancreatic secretion and gastrin release in conscious dogs with duodenal Thomas cannulas. Normal dogs were tested in physiological conditions and with an i.v. infusion of atropine 20 micrograms/kg/h or secretin 0.5 CU/kg/h. The responses were also studied after antral and truncal vagotomy. In the early phase (0-20 min) of the response, before gastric emptying started, antral vagotomy reduced fluid and protein outputs, and truncal vagotomy reduced them still more. Atropine reduced only the protein response. Gastrin release reached a peak after 20-25 min. After antral and truncal vagotomy, gastrin release was reduced within 10 min after the meal. Late-phase (greater than 20 min) pancreatic secretion depended on the presence of chyme in the duodenum. The effects of atropine and antral vagotomy in the cephalogastric phase could be explained by antropancreatic reflexes stimulating fluid secretion (atropine resistant pathway) and protein output (atropine-sensitive pathway). PMID- 1886888 TI - Role of cholecystokinin in pancreatic bicarbonate secretion in dogs. AB - We investigated the effects of endogenous and exogenous cholecystokinin (CCK) on pancreatic exocrine secretion, in particular that of bicarbonate. In six dogs prepared with gastric cannulas and Thomas duodenal cannulas, intraduodenal administration of corn oil (Lipomul) incubated with hog pancreatic enzymes significantly increased pancreatic secretion of both bicarbonate and protein. Increase in pancreatic secretion of both bicarbonate and protein was accompanied by the increase in plasma CCK concentration. However, the increase in bicarbonate as well as protein secretion was blocked by proglumide, a CCK antagonist, given intravenously. In contrast, intraduodenal infusion of undigested Lipomul failed to stimulate the pancreatic exocrine secretion or release of endogenous CCK. These observations indicate that endogenous CCK plays an important role in secretion of both bicarbonate and protein stimulated by digested corn oil. In a group of four dogs with pancreatic fistulas, intravenous infusion of CCK potentiated the stimulatory effect of secretin on pancreatic bicarbonate secretion. The stimulatory effect as well as potentiating effect of CCK on pancreatic bicarbonate secretion was blocked by infusion of proglumide. We conclude that endogenous CCK plays a significant role in fat-stimulated pancreatic secretion, and it is apparent that both endogenous CCK and secretin are equally important for stimulation of pancreatic bicarbonate secretion, which results from potentiation of the action of the two hormones. PMID- 1886889 TI - GLP-1 and GLP-1(7-36) amide: influences on basal and stimulated insulin and glucagon secretion in the mouse. AB - We studied the cellular distribution of glucagon-like peptide-1 (GLP-1) in the pancreas and gut and the effects of GLP-1 and its truncated form, GLP-1(7-36) amide, on basal and stimulated insulin and glucagon secretion in the mouse. Immunofluorescence staining showed that GLP-1 immunoreactivity occurred within peripheral islet cells and in cells located mainly distally in the small intestine and in the entire large intestine. Double-immunostaining revealed that the GLP-1-immunoreactive cells were identical to the glucagon/glicentin cells. Experiments in vivo revealed that basal insulin secretion was stimulated by GLP 1(7-36) amide at the dose levels of 8 and 32 nmol/kg, and by GLP-1 at 32 nmol/kg. Furthermore, GLP-1(7-36) amide showed additive stimulatory influence with glucose (2.8 mmol/kg), the cholinergic agonist carbachol (0.16 mumol/kg), and the C terminal octapeptide of cholecystokinin (CCK-8, 5.3 nmol/kg), when injected at 8 or 32 nmol/kg. In contrast, stimulated insulin secretion was unaffected by GLP-1. Moreover, the glucagon secretory responses to carbachol and CCK-8 were inhibited by GLP-1(7-36) amide but were unaffected by the entire GLP-1. We conclude that GLP-1(7-36) has the potential for being a modulator of islet hormone secretion. PMID- 1886890 TI - Effects of leucine on insulin secretion and beta cell membrane potential in mouse islets of Langerhans. AB - Leucine is known to enhance insulin secretion from islets of Langerhans, and insulin promotes leucine uptake in peripheral tissues. The present studies were designed to elucidate the effects of leucine on glucose responsiveness and stimulus secretion coupling in mouse islets of Langerhans. The effects of 20 mM leucine on insulin secretion and membrane potential were studied over a range of glucose concentrations (0-27.7 mM). Microdissected, perifused pancreatic islets from normal adult mice were used for both studies of insulin secretion and electrophysiology in order to make a close comparison between these measurements. Leucine enhanced the insulin secretion in the presence of 5.6, 11.1, and 22.2 mM glucose. In the presence of leucine, 27 mM glucose inhibited insulin secretion. In the absence of glucose-leucine did not induce electrical activity of the beta cell membrane, whereas in the presence of 5.6, 11.1, and 22.2 mM glucose leucine increased spike frequency. Thus, leucine shifts both the glucose-dependent insulin secretion and electrical activity toward lower glucose concentrations. It is concluded that leucine and glucose share a common metabolic pathway (citric acid cycle) for stimulatory effects. Leucine is deaminated to form 2 ketoisocaproic acid (KIC) and produce NH4+. We propose that in the absence of glucose this increases cytosolic pH, which in turn increases K+ permeability, and inhibits electrical activity and insulin secretion. PMID- 1886891 TI - Analysis of pancreatic serum markers in patients with cystic fibrosis. AB - The occurrence of increased serum concentrations of pancreatic tumor markers CA 19-9, CA 50 and elastase 1 in cystic fibrosis (CF) prompted us to investigate the pancreatic markers DU-PAN-2 and TATI. DU-PAN-2 was measured in serum samples of 48 CF patients, 42 pediatric control patients, and 51 parents of CF children by a competition radioimmunoassay (RIA). A commercially available RIA test kit was used to measure TATI serum levels of 38 CF patients and 40 control patients. Nineteen percent of CF patients, 0% of the control group, and 6% of the parents exceeded the DU-PAN-2 threshold value of 300 U/ml. TATI concentrations were increased (greater than 20 micrograms/L) in 24% of CF patients and in 17% of control patients. The sensitivity-specificity curve of DU-PAN-2 was similar to those of CA 50 and elastase 1 but less discriminating than that of CA 19-9. However, the sensitivity-specificity profile of CA 19-9 can only be marginally enhanced in a range of low specificity by simultaneously determining elastase 1 and/or DU-PAN-2 antigens. TATI does not provide any diagnostic use in CF. PMID- 1886892 TI - Various tumor markers for small pancreatic cancer with special reference to the present status of pancreatic cancer in Japan and our experience over the past 2 years. AB - Various tumor markers for detection of small pancreatic cancer less than 4.0 cm of diameter were evaluated and our recent 2 year experience is presented. Even in T1 cancer, 62.5% of the patients (N = 24) had elevated serum CA 19-9 and 56.5% of the patients also had elevated serum SPan-1. However, that of other markers was less than 30% except for CA 50 (60%). In T2 cancer, the highest sensitivity was observed for SPan-1 (79.6%, N = 54) and that of Ca 19-9 (N = 54) was also high (77.7%). That of other markers was less than 50%. The combination assay of CA 19 9 and SPan-1 in T1 cancer increased sensitivity from a single assay of 62.5% and 56.5%, respectively, to 70%. In T2 cancer, the sensitivity of the combination was 97.1%. All of our cases showed positive results using serum SPan-1 and/or CA 19-9 before confirming the diagnosis with imaging procedures. By applying measurements accurately, the test is a very useful adjunct to the diagnosis of small pancreatic cancer and therefore improves its prognosis. PMID- 1886893 TI - Sandostatin for control of catheter drainage of pancreatic pseudocyst. AB - Primary treatment for pancreatic pseudocyst is evolving from surgical intervention to needle aspiration with catheter drainage. The latter treatment results in a similar rate of resolution but has less patient morbidity. This study evaluated the adjuvant role of Sandostatin, which inhibits basal and stimulated pancreatic secretion, in the management of three patients with pancreatic pseudocysts who had prolonged catheter drainage subsequent to percutaneous drainage. Inhibition of secretion occurred in all three patients, as evidenced by decrease in catheter output, which allowed the catheter to be removed. All three patients have remained asymptomatic for 9, 10, and 15 months, respectively. In summary, Sandostatin decreased persistent catheter drainage from chronic pancreatic pseudocysts. PMID- 1886894 TI - Association of malignant lymphoma with pancreatic adenocarcinoma: a clinicopathologic study of three patients. AB - Three patients with pancreatic adenocarcinoma are studied who had a prior history of malignant lymphoma. No common predisposing factors for the development of pancreatic adenocarcinoma were identified. We conclude that patients with malignant lymphoma who have new or persistent pancreatic masses must be evaluated for the possibility of a second primary neoplasm. PMID- 1886895 TI - A commitment that supports professional autonomy. PMID- 1886896 TI - A crucial journey which needs a standard. Transportation of critically ill patients. PMID- 1886897 TI - A reassessment of oral healthcare. PMID- 1886898 TI - A consideration not to be overlooked. Activated charcoal in acute drug overdoses. AB - Acute poisoning, accidental and incidental, is an everyday occurrence in most emergency departments. The mainstay of emergency therapy is to provide supportive care and limit further absorption of the toxic substance. PMID- 1886899 TI - Adjuncts to the nurse's skills? Advantages and disadvantages of expert systems. AB - Expert systems can, if properly devised, help nurses make clinical decisions. This, the final article in the series, looks at the advantages and disadvantages to their use. PMID- 1886900 TI - Central venous pressure monitoring. PMID- 1886901 TI - A measure of independence. Teaching home blood pressure monitoring. AB - Encouraging hypertensive pregnant women to take their own blood pressure produces reliable and consistent results. It has proved popular among women, enabling them to assess the fluctuations of their blood pressure at first hand and to maintain a sense of control. PMID- 1886902 TI - A means to a long-term goal. Helping colleagues become rational career planners. AB - Successful career counselling offers more than just opportunity awareness. Counsellors must aim to help colleagues assess their own needs and requirements, matching these with openings in the job market. PMID- 1886903 TI - A resource within your budget? Tax liabilities for lease cars and private vehicles. AB - Many community nurses rely on a car for visiting clients in their homes. A basic understanding of the liability of private and lease cars to tax is required if nurses are to avoid undue costs. PMID- 1886904 TI - A natural way to go? Death and bereavement in old age. AB - Death in old age is viewed as 'natural', and bereavement is seen as one of the many losses encountered in later life. All too often, little thought is given to the specific needs of older people in these circumstances. This article seeks to give an overview of their situation, looking at the special features of death and dying in later life. Particular attention will be paid to people who are cared for at home or in community long-stay homes. PMID- 1886905 TI - A premature end to the line. PMID- 1886906 TI - Monthly prostaglandin bibliography prepared by the University of Sheffield Biomedical Information Service. PMID- 1886907 TI - Effects of the PAF-analog and -antagonist CV-6209 on cultured human glioma cell lines. AB - Cell lines of human glioma (U-343 MGa and U-251 MG) and human glia (U-533 CG) origin were cultured as monolayers and exposed to CV-6209, an alkyl-phospholipid analog and antagonist of platelet activating factor. This drug had very potent antiproliferative effects on the studied human glioma cell lines; IC50 was 0.9 microM after 48 h treatment and 0.2 microM after 2 weeks treatment. At these doses no growth inhibitory effect was noted on the normal glia cells. The effects on the glioma cells were reversible in the dose intervals, where cell proliferation, 3H-thymidine and 14C-methionine uptakes were greatly inhibited. The simultaneous administration of platelet activating factor [(R)PAF] did not influence the antiproliferative effects of CV-6209 on the cells cultured as monolayers. The structurally similar analog CV-3988 also had antiproliferative effects, although at 10 times higher concentration than CV-6209. Two other, structurally unrelated, PAF-antagonists (WEB-2086 and TCV-309) gave effects only at very high concentrations. The U-343 MGa cell line was also exposed to CV-6209 when growing as multicellular spheroids. The studies on the spheroid cultures also demonstrated good antitumoral effects with decreases of both the volume growth and the thymidine uptake. The simultaneous administration of (R)PAF reversed the inhibitory effect of CV-6209 on thymidine incorporation. This study demonstrates a strong antitumoral effect at low concentrations of CV-6209. The antiproliferative effects were probably primarily related to the ether-lipid structure and not to the PAF-antagonistic properties. The good antitumoral effect of CV-6209 on both monolayer and spheroid cultures and the possible PAF antagonistic properties are discussed. PMID- 1886908 TI - Mechanism(s) of cytoprotective and anti-inflammatory activity of PGB1 oligomers: PGBx has potent anti-phospholipase A2 and anti-oxidant activity. AB - We postulate that the anti-PLA2 and anti-oxidant activities may account for the broad spectrum protective effects of PGBx that were previously described. These dual properties are demonstrable in vitro, in situ and in vivo, and would have profound effects on stabilization of membrane structure and function, which in turn, would protect organelles, cells, tissues, and organs from inflammation and injury, and possibly alter patterns of aging involving senescence and cell death. PMID- 1886909 TI - Influence of prostaglandin E2 infusion on gastrointestinal electrical activity in the conscious piglet. AB - In 5 conscious piglets with implanted electrodes in the antrum pylori, duodenum, jejunum and ileum, electromyographic activity was recorded daily on a multichannel recorder with a time constant of 0.03 s for intestinal and of 1 s for gastric recordings, and simultaneously integrated at 20 s intervals. PGE2 was infused for 2 h in relatively low doses of 0.1 and 1 microgram/kg/min, to avoid excessive hypersecretion, which would disguise direct effects. Each dose was tested once in each animal with a 1 week interval. Infusion of 0.1 microgram/kg/min revealed no significant changes in antral and small intestinal electrical activity. One microgram/kg/min however induced a strong depression of fast oscillations until the end of the infusion and prolongation of the inhibitory phase in the antrum following a duodenal phase of regular spiking activity. Intestinal segments displayed a prolongation of the quiescent phase and a decrease in the integrated area curve of the phase of irregular spiking activity. Recurrence of the phase of regular spiking activity was unaltered in either segment. These data suggest that the direct effect of PGE2 on gastrointestinal motility in the piglet is a partial inhibition of intestinal contractions. PMID- 1886910 TI - E and F alpha series prostaglandins in developing muscles. AB - Prostaglandins are known to affect myoblast proliferation and fusion in vitro and are putative regulators of in vivo myogenesis. The levels of E and F alpha series prostaglandins in the thigh muscles of chicken embryos were measured by radioimmunoassays and correlated with indicators of muscle development. Just prior to the onset of secondary myogenesis, the amounts of PGE1, PGE2 and PGF1 alpha plus PGF2 alpha per mg of protein were high. In temporal association with myotube formation, the amount of PGE1 and PGE2 per mg of protein decreased. PGF alpha levels also fell, but at a slower rate than observed with the E series prostaglandins. The decreases in the amounts of prostaglandins per mg protein appeared to be due to a decline in the total amount of prostaglandin within each muscle. These observations are consistent with prostaglandins being one of the factors that controls in vivo muscle formation. PMID- 1886911 TI - The effect of Max Epa on low density lipoprotein metabolism: perspectives from an animal model. AB - Rabbits were fed low fat cholesterol-free diets containing casein as the source of protein (27% w/w). One group of 6 animals was supplemented with fish oil (Max Epa; 0.5 ml oil/kg body weight) and compared with 6 animals which were supplemented with a mixture of corn, palm and soybean oils (1:1:1 v/v). VLDL triacylglycerol concentrations were lower in those supplemented with Max Epa. LDL cholesterol and the kinetics of LDL-apo B were unaffected. The results indicate that in endogenously hypercholesterolaemic animals with low triacyglycerol concentrations, casein and possibly other animal proteins, override any effect of this dose of fish oil on LDL metabolism. PMID- 1886912 TI - Effect of chronic underfeeding on uterine glycogen of rats. Influence of indomethacin and nordihydroguaiaretic acid. AB - Glycogen values in uterine strips isolated from normal-fed estrous or diestrous rats, or from rats fed a restricted diet (50% of normal food intake for 25 days) were measured. Determinations were made immediately after killing (0 time or post isolation) as well as after incubation in glucose-free medium (60 min time or post-incubation). The post-incubation levels of glycogen in the uteri from normal fed animals diminished significantly in comparison to post-isolation values, and this decrement was not modified by the addition of indomethacin, nordihydroguaiaretic acid or exogenous prostaglandins E1, E2 or F2 alpha. In rats fed a restricted-diet, the initial glycogen values (0 time) were significantly lower than in normal-fed controls, but did not decline further after incubation in glucose-free medium (60 min time). The addition of indomethacin, acetylsalicylic acid or of nordihydroguaiaretic acid led to a significant fall in the glycogen levels, and exogenous PGE1, PGE2 or PGF2 alpha failed to alter the effects of the inhibitors. The values of PGE and PGF prostaglandins release to the medium by the uterus from restricted-diet rats did not differ from those obtained in the experiments with normal-fed animals. Administration of 17-beta estradiol to restricted-diet rats led to suppression of the effects of this diet on the glycogen concentration. The above results indicate that in rats subjected to a prolonged period of dietary restriction, the uterine glycogen becomes responsive to the effects of cyclooxygenase and lipoxygenase inhibitors, suggesting the operation of some regulatory mechanism during critical periods of nutrition. PMID- 1886913 TI - Inhibitory effects of beta adrenoceptor antagonist, atenolol, on the thromboxane system in the kidney of spontaneously hypertensive rats. AB - We attempted to investigate the alterations in the vasoconstrictor thromboxane (TXA2) system in the kidney when spontaneously hypertensive rats (SHR) were treated subchronically with atenolol, a beta 1-adrenoceptor antagonist. Atenolol treatment (30 mg/kg body weight per day for 2 weeks) reduced systolic blood pressure by 11%, being accompanied by a decrease in heart rate. This treatment strikingly decreased thromboxane content in the renal cortex by 48% (p less than 0.05), whereas the tissue content was unaltered for prostaglandin E2 (PGE2) or slightly decreased for prostacyclin (PGI2). These alterations in the eicosanoid system led to an increase in the ratio of PGE2/TXA2 and of PGI2/TXA2. Similarly, thromboxane content in the renal papilla was lowered significantly with atenolol treatment, which raised the ratio of PGE2 to TXA2. Thromboxane reduction was not observed in the aortic walls and heart. However, in the vascular walls, PGI2 synthesis was markedly stimulated with atenolol treatment, resulting in an increase in the ratio of PGI2 to TXA2. Thus, these data indicate that subchronic atenolol-treatment inhibits the thromboxane system in the kidney, thereby shifting the eicosanoid system towards a vasodilator state. These alterations contribute, in part, to the anti-hypertensive properties of atenolol in genetic hypertension. PMID- 1886914 TI - [The significanse of microsomal ethanol oxidation systems for the metabolism of drugs and pollutants]. PMID- 1886915 TI - [2-Dichloromethyl-naphthimidazole quinones. 4. Heterocyclic 1,4-naphthoquinine derivatives]. AB - 2-Arylamino-3-dichloroacetylamino-1,4-naphthoquinones 4 show in ethanolic hydrochloric acid the same reactivity as the corresponding 3 monochloroacetylamino-1,4-naphthoquinones 3. After cyclisation from 4 to 6, 6 dehydrates to give 2-dichloromethyl-4,9-dihydro-1-phenyl-1H-napth [2,3 d]imidazole-4,9-diones 8. Elimination of dichloromethane from 6 to 9 is not observed. The reaction of 4c in alkaline DMSO solution indicates, that ring closure to 3-hydroxy-benzo[g]quinoxalinetriones 2 is possible. The microbiological activity from 7 and 8 has been proved. PMID- 1886916 TI - Clean-up and determination of sodium valproate in serum by high-performance liquid chromatography with fluorimetric detection. AB - A method is reported for the determination of the anticonvulsant sodium valproate in serum by fluorimetric detection. HPLC is performed on a reversed-phase column with a mobile phase of acetonitrile/water (65:35, v/v) with cyclohexane carboxylic acid as an internal standard. Samples were derivatized with 4 bromomethyl-7-methoxycoumarin and the optimized conditions are reported. PMID- 1886917 TI - [The toxicity of surface-active substances for emulsifying perfluorocarbon compounds as components of blood substitute preparations]. AB - Perfluorocarbons are insoluble in water. For being used as oxygen carriers in blood substitutes they therefore have to be emulsified. Using surfactants in the living organism a compromise on the emulsifying effect and toxicity is to be made, since good emulsifiers do also affect biological membranes. The influence of molecule parameters of surfactants on toxicity was studied in this paper. PMID- 1886918 TI - [The social role of the pharmacist in Germany between 1800 and 1870]. PMID- 1886919 TI - Quinazolinones. 19. Communication [1]: synthesis and evaluation of some CNS depressant properties of 3-(2-[(5-aryl-1,3,4-oxadiazole-2-yl)amino]acetamido)-2 methyl-4 (3H)-quinazolinones. PMID- 1886920 TI - Synthesis and antibacterial activity of some new mesoionics. PMID- 1886921 TI - Determination of D(-)penicillamine by potentiometric titration. PMID- 1886922 TI - Stability of sultamicillin tosylate in artificial gastric and intestinal media. PMID- 1886923 TI - Effect of metabolites from linoleic acid on migratory behaviour of endothelial cells. PMID- 1886924 TI - [Pharmacologic modulation of central noradrenergic mechanisms and the effect of selected substances on chemically-induced seizures: the maximal N-methyl-d,l aspartate seizure test (mouse)]. PMID- 1886925 TI - Particle track structure and its correlation with radiobiological endpoint. AB - One of the possible ways to classify track structures is application of the conventional partition techniques of analysis of multidimensional data to the track structure. Using these cluster algorithms this paper attempts to find characteristics of radiation reflecting the spatial distribution of ionizations in the primary particle track. Absolute frequency distributions of clusters giving the mean number of clusters produced by radiation per unit of deposited energy have been computed for radiation of different qualities. The results were compared with the published experimental data of cell inactivation. For particular biological objects the critical properties of radiation correlating with the cell inactivation can be found and it seems that the occurrence of a cluster of at least four ionizations formed in a domain of approximately 2-3 nm correlates with the induction of double strand break. PMID- 1886926 TI - Monte Carlo techniques in medical radiation physics. PMID- 1886927 TI - Parallel simulated annealing for emission tomography. AB - A method for implementing simulated annealing in parallel to speed up the execution of emission tomography (ET) image reconstruction is presented. A high degree of parallelism can be attained by using a parallel-acceptance partitioning strategy, in which perturbations to subsets of the estimate are evaluated in parallel. However because the point spread function in ET imaging systems is globally dependent, processors cannot update the current estimate independently. Consequently, processors must be synchronized each time a perturbation is accepted to avoid introducing error. This can produce excessive communications overhead, especially when the acceptance rate is high. In this paper an energy function is constructed to reduce the synchronization requirements by using a reformulation of the log-likelihood function from the expectation maximization (EM) algorithm. The approach is to change the global dependence in the energy function from the current estimate to the estimate generated during the last iteration. The synchronization requirements for guaranteed convergence are then significantly reduced from once per acceptance to once per iteration. This parallel implementation on 54 Inmos T800 transputers connected in a ring topology resulted in execution times that were almost 50 times faster than on a VAX 8600. PMID- 1886928 TI - A normalization technique for 3D PET data. AB - Prior to reconstruction, emission data from a multi-ring PET camera must be corrected (normalized) for variations in detector sensitivity. The appropriate correction coefficients are obtained by measuring the response of all coincidence lines to a calibrated source of activity (a blank scan). State-of-the-art cameras may contain up to a million such lines of response (LORs), and therefore around 400 million counts will be required to calibrate each LOR to a statistical accuracy of 5%. Alternatively, by modelling the LOR sensitivity as the product of the individual detector efficiencies and a geometrical factor, a calibration procedure has been proposed which requires the determination of only 6000 parameters from this same data set. A significant improvement in the statistical accuracy of the coefficients can therefore be expected. Recently, multi-ring scanners have been operated with the septa retracted, increasing the number of measured LORs by a factor of eight. The acquisition of the calibration data necessary to achieve adequate statistical accuracy then becomes prohibitive. We show that, by modelling the LOR sensitivity, it is possible, with certain approximations, to normalize a septa-retracted emission data set with good accuracy. The input to the model is a high statistics blank scan acquired with the septa extended, which offers a number of practical advantages. PMID- 1886929 TI - Determination of fat content of burbot (Lota lota) liver with low field MR imaging (0.04 T). AB - A reconstructed separate fat image was used for studying the fat content of the liver of 12 dead and six living fasting burbots (Lota lota) in a 0.04 T magnetic field with olive oil as a reference. The correlation between the MR intensities and the results of the cytological, histological and chemical fat measurements, as well as chemically measured water, collagen and total protein contents were examined. The MR signal intensity in reconstructed fat images correlated well with the changes in fat content of the liver in living fish (r = 0.69, P = 0.0014). Also the contents of water (r = -0.66, P = 0.003) and total protein (r = -0.91, P = 0.013) correlated significantly with the MR signal intensity. The reconstructed fat image is thus a reliable method for following the changes in tissue fat content. The living burbot is an applicable test animal for studying the hepatic fat content with MR. PMID- 1886930 TI - Dosimetry of 106Ru eye applicators with a p-type silicon detector. AB - Beta emitting 106Ru-applicators are used to treat choroidal melanoma. In order to improve the accuracy and simplify the dosimetry of these applicators, the suitability of using a p-type silicon semiconductor detector has been investigated. The detector is calibrated in a low energy electron beam. An important property of the detector for this application is that the linear scattering power of the epoxy resin that surrounds the silicon crystal is within 1% of that for water, in the energy interval of interest. Furthermore the variation in the mass collision stopping power ratio water to silicon is within 4% in this energy interval. The accuracy of the dose-rate measured with the detector is about 5% for this application. PMID- 1886932 TI - Lasers in medicine. PMID- 1886931 TI - Current and future trends in laser medicine. AB - In this overview, a number of the major current, and possible future developments in laser medicine are explored. In therapeutic applications, particular emphasis is given to obtaining selectivity in tissue targets and interaction mechanisms in order to achieve specific biological effects. This includes spatial confinement of thermal damage by pulsed laser irradiation and targetting by exogenous photothermal or photochemical chromophores. The potential for diagnostic applications of lasers in medicine is illustrated primarily by various in vivo spectroscopic techniques. Both therapeutic and diagnostic applications will rely increasingly on the development of total systems in which lasers will form only one, albeit an essential, part. Numerous scientific and technical problems need to be solved in order to realize the full clinical potential of the many new concepts in laser medicine. The impetus for such progress will come from integrated, multidisciplinary collaborations between medical, scientific and industrial groups. PMID- 1886933 TI - Photokeratitis from 193 nm argon-fluoride laser radiation. AB - The threshold for photokeratitis at 193 nm was obtained for the rabbit cornea using an ArF excimer laser. Because ablation occurs at a level below that for photokeratitis, it was necessary to expose the cornea to a lengthy series of low energy exposures. It is concluded that the 193 nm photons have such a shallow penetration depth, being limited to the outermost epithelial cells, that classical photokeratitis occurs from the fluorescence emitted at the corneal epithelial absorption site. An intact tear film may help to protect the cornea from low-level, scattered 193 nm laser radiation. PMID- 1886934 TI - Comparison of distribution and photodynamic effects of di- and tetra-sulphonated aluminium phthalocyanines in normal rat colon. AB - We have previously reported photodynamic therapy of normal rat colon using aluminium sulphonated phthalocyanine (AISPc). In that study, the AISPc used was a mixture of phthalocyanines of different degrees of sulphonation. Phthalocyanines of defined degrees of sulphonation have recently become available and we compared the distribution of the di- and tetra-sulphonates (AIS2Pc and AIS4Pc) in rat colon and colon wall structures employing both chemical extraction and fluorescence photometry using a charge coupled device imaging system. Also, the photodynamic effects produced by these components in rat colon were compared at various times after photosensitization. After intravenous photosensitizer administration using equimolar doses, the concentration of AIS2Pc in colon fell off more rapidly with time than AIS4Pc. Differences were noted in the microscopic distribution of these compounds, with the di-sulphonate exhibiting peak fluorescence in colon wall structures by 1 h after photosensitization, while mucosal fluorescence with the tetra-sulphonate peaked at 5 h. Fluorescence was also lost from the colon wall much more slowly with the tetra-sulphonate, which tended to be retained in the submucosa. Maximum photosensitizing capability was seen at 1 h with AIS2Pc and no lesions could be produced with photodynamic therapy at 1 week, with up to 5.65 mumol/kg. With AIS4Pc (5.65 mumol/kg), while no lesions could be produced with light treatment at 1 h, photodynamic therapy at 1 week produced lesions only slightly smaller than those produced with treatment at 48 h (the time of maximum effect), and significant photosensitization was present at 2 weeks.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1886935 TI - Comparative studies of femtosecond to microsecond laser pulses on selective pigmented cell injury in skin. AB - Threshold radiant exposures for grossly apparent immediate whitening and ultrastructural alterations of melanosomes in black guinea pig skin were determined for a series of red visible laser pulses ranging from 4 x 10(-4) to 6.5 x 10(-14) s. Threshold exposures for melanosomal injury were found to be independent of pulsewidth when the pulsewidths were below the estimated thermal relaxation time of melanosomes. Threshold radiant exposures for melanosomal injury were found to increase when the pulsewidths were approximately equal to or above the thermal relaxation time of melanosomes. At longer pulse durations, fracturing of melanosomes was not observed despite the longer exposures necessary for injury. Instead, perimelanosomal vacuoles were noted. These findings are consistent with the theory of selective photothermolysis and provide evidence for the thermal initiation of melanosomal disruption. PMID- 1886936 TI - The melanosome: threshold temperature for explosive vaporization and internal absorption coefficient during pulsed laser irradiation. AB - The explosive vaporization of melanosomes in situ in skin during pulsed laser irradiation (pulse duration less than 1 microsecond) is observed as a visible whitening of the superficial epidermal layer due to stratum corneum disruption. In this study, the ruby laser (694 nm) was used to determine the threshold radiant exposure, H0 (J/cm2), required to elicit whitening for in vitro black (Negroid) human skin samples which were pre-equilibrated at an initial temperature, Ti, of 0, 20, or 50 degrees C. A plot of H0 vs Ti yields a straight line whose x-intercept indicates the threshold temperature of explosive vaporization to be 112 +/- 7 degrees C (SD, N = 3). The slope, delta H0/delta Ti, specifies the internal absorption coefficient, mua, within the melanosome: mua = rho C/(slope(1 + 7.1 Rd)), where rho C is the product of density and specific heat, and Rd is the total diffuse reflectance from the skin. A summary of the absorption spectrum (mua) for the melanosome interior (351-1064 nm) is presented based on H0 data from this study and the literature. The in vivo absorption spectrum (380-820 nm) for human epidermal melanin was measured by an optical fiber spectrophotometer and is compared with the melanosome spectrum. PMID- 1886937 TI - Application of charge-coupled device technology for measurement of laser light and fluorescence distribution in tumors for photodynamic therapy. AB - Laser and fluorescence light distributions with applications for photodynamic therapy were measured in mouse tumors using a non-invasive electronic optical imaging system. The system consists of a liquid-nitrogen-cooled, charge-coupled device (CCD) array camera under computer control with 576 x 384 detection elements having dimensions of 23 microns x 23 microns. The available dynamic range of the array is approx. 10(3), and the effective wavelength range is 400 1000 nm. An interstitially placed cylindrical diffusing optical fiber was used to provide tumor illumination. The light distribution pattern from the fiber was determined by immersing the cylindrical diffusing tip in a fluorescing solution and recording the emission image. Fluorescence imaging facilitates an accurate measurement of light intensity distribution while avoiding problems associated with the directional nature of other detection methods used with diffusing fibers. Radiation-induced fibrosarcoma tumors on C3H mice were grown to about 1 cm diameter for in vivo recording of light distribution from the tumor volume and for determination of effective light penetration distance at 18 wavelengths in the range 458-995 nm. Endogenous tumor fluorescence and Photofrin II fluorescence intensity were measured over the wavelength range 585-725 nm to investigate the possible application of CCD imaging technology for drug distribution measurements. Model experiments were begun to evaluate the relative importance of potential distortions of light distribution measurements using this approach. PMID- 1886938 TI - Enhancement of antitumor drug cytotoxicity via laser photoactivation. AB - We investigate the efficacy of daunomycin, some imino- and amino-substituted daunomycin analogues and the disubstituted aminoanthracenedione, mitoxantrone, in photosensitizing short-term cell kill upon irradiation in the long wavelength visible range, during incubation of Fisher rat thyroid cells with the drugs. While all compounds exhibit similar cytocidal effects on our cell line, in the absence of irradiation, administering 86 J/cm2 at wavelengths either coincident or close to drug absorption peaks causes greater enhancement in cell mortality for the 4-demethoxydaunomycin analogues than either the parent drug or its 5 imino-derivative. A lower enhancement is observed with mitoxantrone. In particular, C50 doses (i.e. concentrations that would kill 50% cells) as low as approximately 10(-9) M are found for both 6- and 11-amino 4-demethoxydaunomycin, compared with the values obtained in the absence of light, which are 2.59 x 10( 4) and 0.43 x 10(-4) M, respectively. Our previous studies of the photophysical and photochemical properties of the excited states of these drugs, and ESR and spin trapping studies of photosensitized generation of singlet oxygen, which were extended in this work to include mitoxantrone, indicate that the cytocidal effects proceed via type I rather than type II mechanisms. PMID- 1886939 TI - Fluorescence imaging and point measurements of tissue: applications to the demarcation of malignant tumors and atherosclerotic lesions from normal tissue. AB - The possibilities of using laser-induced fluorescence for tissue diagnostics are discussed. The tissue types investigated are malignant tumors and atherosclerotic lesions. Studies with natural autofluorescence as well as with fluorescent tumor markers are included in this paper. Fluorescence emission and decay data are presented for some tissue chromophores contributing to tissue autofluorescence. Optical spectroscopic characteristics of fluorescent malignant tumor markers are analyzed and instrumental designs for clinical applications are discussed. Images recorded with a multicolor fluorescence imaging system developed in Lund are presented. PMID- 1886940 TI - Laser thermal ablation. AB - Continuous wave and pulsed laser ablation of tissue is described as an explosive event. A subsurface temperature maximum and superheated tissue produce high pressures that eject fragments from the tissue. Decreased water content due to dehydration and vaporization decreases thermal conductivity which reduces heat conduction. Also, a decrease in water content dramatically alters the local rate of heat generation of laser radiation above 1.3 microns since water is the primary absorber. In contrast, at UV wavelengths protein and DNA are the primary absorbers so destruction of tissue bonds is due to direct absorption of the laser light rather than heat transfer from water. PMID- 1886941 TI - Pathologic analysis of photothermal and photomechanical effects of laser-tissue interactions. AB - Pathologic analysis of the biologic effects and mechanisms of laser-tissue interactions requires correlation of the irradiation parameters with the biologic status and response of the target tissues over time. The photobiologic mechanisms of laser-induced tissue injury can be separated into three categories, photochemical, photothermal and photomechanical. Anatomic pathologic analysis of laser-induced lesions reveals alterations that represent either specific markers of the photobiologic mechanism or non-specific reactions to tissue injury. Repair, regeneration and wound healing of laser induced lesions appear to be non specific responses to the type of tissue damage rather than the photobiologic mechanism producing the lesion. PMID- 1886942 TI - Interstitial laser hyperthermia for the treatment of hepatic and pancreatic tumours. PMID- 1886943 TI - Phthalocyanines as photodynamic sensitizers. PMID- 1886944 TI - Preference of Old World monkeys for amino acids and other gustatory stimuli: the influence of monosodium glutamate. AB - Monosodium glutamate (MSG) is widely considered to enhance the flavor of beef, chicken, fish, and vegetables. This effect may be due to the interaction of glutamate with free amino acids or other basic taste stimuli present in these foods. A single-bottle test was used in order to test the preference of Old World monkeys for an extended array of gustatory stimuli individually and in combination with MSG. Six male cynomolgus monkeys, maintained on an 18-h water deprivation schedule, were given 30 min access daily to a sapid stimulus or distilled water. The following stimuli (selected on the basis of prior experimentation) were tested alone and in combination with 0.03 M MSG: sucrose, fructose, glucose, maltose, polycose, sodium saccharin, glycine, sodium chloride, hydrochloric acid, tartaric acid, malic acid, citric acid, quinine hydrochloride, urea, and beef broth. The L-isomers of the following free amino acids also were tested: alanine, histidine, phenylalanine, proline, serine, valine. The addition of MSG to the stimuli listed above had no significant effect upon the monkeys' preference or aversion thresholds. Most suprathreshold stimuli that the monkeys neither preferred nor avoided were unaffected by the addition of MSG. The monkeys' preference for sugars was adversely affected in mixtures containing MSG, but other stimuli that humans report to be sweet tasting (alanine, glycine, polycose) were unaffected. The data from the present experiment demonstrate that MSG was capable of altering the monkeys' preference for some but not all of the gustatory stimuli tested.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1886945 TI - Human development and umami taste. AB - Previously we demonstrated that in very brief, one-bottle intake tests, human infants, both well nourished and protein calorie malnourished, ingested greater amounts of soup with added MSG compared with soup alone. The potentiating effect of MSG in plain aqueous solution was tested in the current experiments. In contrast to data with sucrose and salt solution, where infants preferentially ingest these compounds compared with a water diluent, aqueous MSG solutions were rejected relative to water. The implications of this observation for understanding the mechanisms of MSG perception and pleasantness were discussed. PMID- 1886946 TI - Effects on metabolic and hormonal parameters of monosodium glutamate (umami taste) ingestion in the rat. AB - Umami taste appears to signal, at the gustatory level, the intake of proteins, therefore the working hypothesis was: does umami taste of a monosodium glutamate (MSG) solution elicit changes in both glucagon and insulin release, similar to those elicited by amino acids, and consequently, changes in plasma glucose and in overall cellular metabolism? In a first experiment, rats were equipped with indwelling jugular and oral catheter and serial samplings were made in the free moving, undisturbed rat before and after an oral or IV infusion of MSG (0.05 M). None of the plasma parameters showed any significant response. In a second experiment, energy expenditure was monitored by means of an original computer based calorimeter capable of calculating, besides the classical parameters, resting metabolism in a moving animal (designated by background metabolism). The addition of MSG to a low calorie, low-protein meal did not modify background metabolism or respiratory quotient. Therefore MSG ingestion does not by itself affect plasma levels of hormones of glucose and protein metabolism, total metabolism rate, or nutrient utilization. However, examination of individual data and those from a pilot experiment for future work suggests that MSG becomes an efficient metabolic effector if added to a caloric diet, and so enhances proper thermogenesis of macronutrients. PMID- 1886947 TI - Interaction of MSG taste with nutrition: perspectives in consummatory behavior and digestion. AB - Studies in the taste system of mammals indicate that monosodium glutamate (MSG) produces a unique taste sensation termed umami. As a derivative of glutamic acid, MSG is a naturally occurring nutrient in many foods; its commercial use to improve food palatability for humans is well documented. Behavioral studies with experimental animals have revealed that preference for MSG in solutions and selection of MSG-flavored diets can be explained by sensory means with no appreciable effects on preference by postingestive consequences. However, preference for umami-flavored fluids is reduced by feeding rats low-protein diets or low quality protein. MSG-flavored diets, initially unpreferred, were subsequently highly selected. However, the adulteration of diets by MSG either did not or only slightly increased food intake. In light of the significant contribution of MSG to diet taste, apparently as a signal coupled to dietary proteins, physiological studies have been initiated to reveal its role as a stimulator of the cephalic phase of pancreatic exocrine secretion. Modified sham feeding experiments with dogs have shown that oral stimulation by MSG produced significant stimulation of both pancreatic flow and protein output in conscious dogs. PMID- 1886948 TI - Time-quality tracking of monosodium glutamate, sodium saccharin, and a citric acid-saccharin mixture. AB - The temporal patterns of taste-quality descriptors evoked by 1000-ms duration stimulus liquids flowed through a closed delivery system over the anterodorsal tongue tip region were indicated using touch-typing on a computer keyboard. Single keys corresponded to the taste words of a 23 item code. A computer monitor displayed for subjects the keys pressed and when they were pressed, starting at stimulus delivery. For 2 mM sodium saccharin (NaSac), 75% of the responses were "sweet," 6.5% "sugar"; for NaSac in 10 mM citric acid (ArtLem), 43% "sour," 20% "citrus," and 11% "sugar"; for 214 mM monosodium glutamate (MSG), 28% "salty," 14% "sour," and 10% 1st "soapy," then "no taste," and finally "bitter." Distilled water received "no taste" on all trials. Response durations were 657 ms for ArtLem, 594 ms for NaSac, 577 ms for MSG. MSG yielded multiple quality responses on 25.5% of the trials; ArtLem, 9%; and NaSac, 1%. These results are compared with temporal patterns for taste intensity and with unrestricted verbal descriptions of the solutions. PMID- 1886949 TI - Monosodium glutamate as a palatability enhancer in the European diet. AB - Can monosodium glutamate (MSG) augment palatability in foods of the occidental diet? Its effects on the palatability of two experimental foods were investigated in 36 healthy young men and women. MSG improved palatability ratings, with an optimum at 0.6%. Weekly tests of free intake showed that subjects fed the experimental foods with 0.6% MSG added ate progressively more and faster, indicating increasing palatability with repeated exposure. The effects of MSG on familiar foods were investigated in a group of 65 institutionalized elderly persons. Spontaneous intake was measured at lunch time on 12 test days. Target foods (soup and vegetable) were served either without or with 0.6% MSG added. MSG facilitated intake of some but not all target foods, and was associated with positive (increased calcium and magnesium intake) or adverse (increased fat intake) nutritional effects. It is concluded that MSG can act as a palatability enhancer in the context of the French diet. It can facilitate long-term intake in both young and elderly persons but it should be utilized cautiously so as to improve nutrition. PMID- 1886950 TI - Taste cells in the gut and on the tongue. Their common, paraneuronal features. AB - Chemoreception of foodstuff in the gut is performed by endocrine cells dispersed in the gut epithelium. They are bipolar cells extending an apical process to the gut lumen and releasing their messenger substances from the cell base in response to the apical stimuli. The cells share cell-biological features with neurons and are classified as paraneurons. Noteworthy, the gut paraneurons do not seem to be stimulated by monosodium glutamate (MSG) as our dog experiment indicates. Administration of 50 mM MSG into the duodenal loop of anesthetized dogs did not cause changes in the volume and protein output in the pancreatic juice. The gustatory cells in the taste bud show essentially the same structure and function as the gut endocrine cells. A single gustatory cell type (type III) seems to receive different chemical stimuli, whereas different endocrine cell types in the gut react to different stimuli. The gustatory cells possess numerous peptidergic type granules besides synapse-associated small clear vesicles. The former granules, in the guinea pig and dog, are abundant in the cytoplasm, giving an endocrine-like appearance to the cell. Peptidic signal substances contained in the granules remain to be identified. Comparison of the gustatory cells in the taste bud with the endocrine cells in the gut and with other paraneurons may put into front certain hitherto unexplored structures and functions of the cells. PMID- 1886951 TI - Neuronal responses of the nucleus tractus solitarius to oral stimulation with umami substances. AB - In order to investigate coding mechanisms of special taste modality (umami), responses of neurons within the nucleus tractus solitarius (NTS) to oral stimulation with monosodium glutamate, disodium 5'-inosinate (IMP) or their mixture were recorded in the conventional electrophysiological method. Results obtained were as follows: Neither MSG-best nor IMP-best neuron was recorded within the NTS as in the primary taste afferents. Some of the sucrose-best neurons, NaCl-best neurons and HCl-best neurons responded to oral stimulation with MSG or IMP. A remarkable synergistic effect was observed in all of the sucrose-best neurons and in some of the NaCl-best neurons but not in all of the HCl-best neurons, when the mixed solution of MSG and IMP was applied into the oral cavity. As to the sucrose-best neurons, potency of the synergism was positively correlated with the responsiveness to sucrose. No correlation was recognized between them in the case of NaCl-best neurons. These results suggest a view that the sucrose-best neurons and the NaCl-best neurons which show the synergism may participate in coding umami taste. PMID- 1886952 TI - Nutritional studies of the roles of dietary protein levels and umami in the preference response to sodium chloride for experimental animals. AB - Previously we found that appetite or preference for sodium chloride depends not only on a genetic factor, but also on the nutritional status, i.e., dietary protein levels. To determine whether all kinds of protein had reducing effects on sodium chloride intake, the effect of dietary protein source on appetite or preference for sodium chloride was studied. It was found that the effect depended not only on protein levels, but also on the protein sources, i.e., amino acid patterns of diets. On the other hand, the turnover time of gustatory taste bud cells was measured by the pulse-labeled method using 3H-thymidine. It was found that the turnover time of gustatory cells in the taste buds of rats fed a low protein diet was longer than in rats fed a high-protein diet. This suggested that some reduction of receptor functions may occur with low-protein diet. It was found that the dietary protein levels and umami also modified appetite or preference for alcohol solutions. PMID- 1886953 TI - [Comment on the contribution, "Neuropsychiatric disorders caused by organic solvents", by M. v. Bose and M. Zaudig]. PMID- 1886954 TI - [Guidelines for interaction by the therapeutic team in inpatient treatment of patients with chronic neurotic disorders]. AB - In treatment of in-patients with chronic neurotic disorders we tried both to reduce distress in the therapeutic team (doctors, nurses, other therapists) as usually caused by those patients, and to improve outcome of treatment. Therefore, three to five guidelines on how to deal with the patient were given to the therapeutic team, and illustrated by possible literal statements to the patient. The guidelines aimed at a general interactional approach to the patient and did not determine specific therapeutic interventions. They were set up following principles of Brief Therapy as developed at the Mental Research Institute in Palo Alto. Results of our intervention in treatment of ten patients are reported. The therapeutic team rated the guidelines generally as positive. The therapeutic outcome varied greatly. A comparison with a matched pair control group showed a favourable tendency. Initial ratings by the team of the prescriptions predicted eventual improvement of the patients. PMID- 1886955 TI - [Adverse effects of long-term psychopharmacologic therapy on sexual functions]. AB - 103 patients who were in a psychopathologically relatively stable condition and under long-term psycho-pharmacological treatment on an outpatient basis, were questioned on sexual functional disorders and changes in sexual behaviour, basing on a semistructured interview. This is of particular importance with regard to compliance problems in long-term therapy. 50% of the patients stated that there had been changes from the beginning of the psychiatric disorders, mostly as functional sexual disorders (42%). Multifactorial causes were presumed in most of the cases; the medication was thought to be solely responsible in only 15% of all the cases (expert rating). Schizophrenic patients under neuroleptic treatment were most frequently affected by functional disturbances. In some of the patients of the total random sample (36 patients) medication was changed under experimental conditions for a period of four weeks. Improvement of the sexual function was most frequently stated whenever a medication was given with a reduced dosage; however, the examined partial random sample is very small. PMID- 1886956 TI - [Public vocational integration: a new method for integrating psychiatrically handicapped patients into occupational life?]. AB - Suitable conditions of employment represent a central factor in the rehabilitation of mentally ill people. In this case both the normality of the job -as felt by the individual--and adequate instrumental and social working conditions are determining factors. According to the ideas of the Workshop for the Handicapped (Werkstatt fur Behinderte) and the movement for the Self-help Firms, the integration of the mentally ill into normal jobs is an important step in the right direction. Appropriate preparations (i.e. assessment of patients' working capabilities and the drawing up of expectation profiles, work-preparation measures) and well-organized follow-up care are required to achieve this. Statutes which make access easier must be created in the fields of both labour and social law in order to make integration into the labour market possible. In this respect the non profit-making provision of employees (Gemeinnutzige Arbeitnehmeruberlassung) represents a model. The procedure has been described and first experiences with its realization have been reported upon. PMID- 1886957 TI - Weak sensory stimuli induce a phase sensitive bradycardia. AB - We attempted to demonstrate that significant perceptual stimuli would induce different degrees of heart rate deceleration depending on when (phase) in the cardiac cycle they occurred. Relative to previous work, we concurrently examined a number of factors that might alter the amplitude of such a cardiac cycle time effect. Stimulus intensity and presence or absence of a speeded response were manipulated. Liminal stimuli and a perceptual rather than motor set were expected to maximize any cardiac cycle time effect. Respiratory phase, length of average interbeat interval, and number of trials were also investigated. Twenty-four college aged, male volunteers were randomly separated into equal groups receiving instructions either to judge which of two weak visual stimuli occurred or to execute a speeded, discriminative response to the stimuli. Discriminative stimuli were presented at either 0, 150, 250, 350, or 500 ms after the R-wave of the electrocardiogram. Stimuli were presented with an intensity that had yielded either 63% or 90% correct detections in a prior psychophysical assessment. A phase dependent deceleration occurred after both intensities of stimuli. Poststimulus deceleration was greater for stimuli in early to mid cycle as suggested by earlier work. As expected, this result was clear when the stimuli were presented during the expiratory phase of respiration. Neither perceptual/motor set nor stimulus intensity altered the phase sensitive deceleration. Thus, phase sensitive deceleration was confirmed using demanding sensory stimuli and an improved representational technique. PMID- 1886958 TI - Exaggerated sympathetic nervous system response to extended psychological stress in offspring of hypertensives. AB - The cardiovascular responses of 24 healthy young adult males with a parental history of hypertension and 24 males without a parental history of hypertension to an extended active-coping psychological stressor were compared under three drug conditions: placebo, the beta 1-blocking agent metoprolol, and the alpha 1 blocking agent prazosin. In the placebo condition, offspring of hypertensives exhibited significantly greater heart rate, blood volume pulse, and forearm blood flow responses to the task. They also exhibited a significantly greater initial decrease in forearm vascular resistance, which, in contrast to the offspring of normotensives, was no longer significantly different from baseline levels by the end of the session. No group differences in blood pressure response were observed. Metoprolol eliminated the differences in heart rate and forearm vascular resistance responses. Prazosin eliminated the difference in blood volume pulse response and elicited a sustained group difference in forearm vascular resistance. These results implicate the sympathetic nervous system in the exaggerated cardiovascular responsivity to psychological stress in individuals with a family history of essential hypertension. They also suggest that the pattern of increasing vascular resistance in response to this stressor observed in this and other studies in this laboratory reflects alpha-adrenergic activity and not neurohumorally independent autoregulation. PMID- 1886959 TI - Maturation of prestimulation-induced startle modulation in girls. AB - This study of the maturation of prestimulation-induced modulation of startle in 4 to 8-year-old girls and young women demonstrated significant effects of age on both startle amplitude and onset latency modulation. Prestimulation with nonstartling tones resulted in strong inhibition of both amplitude and latency of the startle blink reflex in adults when 25-ms tones preceded the startling stimuli by 120 ms or 250 ms. Following sustained prestimulation for 2000 ms, the adults showed weak nonsignificant response facilitation. Eight-year-old girls showed mature inhibitory startle amplitude modulation, but significantly less inhibition of onset latency compared to adults. Preschool girls showed significantly less amplitude and latency inhibition and more facilitation than 8 year-olds and adult women. These findings in female subjects were very similar to those obtained by Ornitz, Guthrie, Kaplan, Lane, and Norman (1986) in male subjects. Gender differences were limited to the 8-year-old age group. The 8-year old girls showed significantly less startle amplitude inhibition than 8-year-old boys following the 120-ms and 250-ms prestimulation intervals and less latency facilitation following 2000 ms of sustained prestimulation. In general, these findings suggest that brainstem mechanisms that mediate startle response modulation undergo development during early childhood and do not mature until about 8 years of age in both male and female subjects. The results are discussed in relation to studies of gender effects on development of other neurophysiological variables and to maturation of the nervous system. PMID- 1886960 TI - Removal of the ocular artifact from the EEG: a comparison of time and frequency domain methods with simulated and real data. AB - Frequency-dependent transfer from EOG to EEG may be insufficiently accounted for by simple time domain regression methods (Gasser, Sroka, & Mocks, 1986; Woestenburg, Verbaten, & Slangen, 1983). In contrast, a multiple-lag time domain regression analysis, using lagged regression of EEG on EOG, must theoretically account for both frequency dependence and independence. Two data sets were constructed, in which the transfer from EOG to EEG was either frequency independent (constant gain) or frequency-dependent. Subsequently, three different correction methods were applied: 1) a simple regression analysis in the time domain; 2) a multiple-lag regression analysis in the time domain; and 3) a regression analysis in the frequency domain. The major results were that, for data set 1, the three methods constructed the original EEG equally well. With data set 2, reconstruction of the original EEG was achieved reasonably well with the frequency domain method and the time domain multiple-lag method, but not with simple time domain regression. These three correction procedures were also applied to real data, consisting of concomitantly recorded EEG and high-variance EOG series. No appreciable differences in outcome of the three methods were observed, and estimated transfer parameters suggested that these data were marked by weak frequency dependence only, which can be accounted for by simple time domain regression (and also by the other two methods). PMID- 1886961 TI - Cortical activity elicited by changes in auditory stimuli: different sources for the magnetic N100m and mismatch responses. AB - Magnetic responses to frequent and infrequent auditory stimuli, all presented in the same stimulus block in randomized order, were recorded. The standard stimuli, comprising 90% of all the stimuli, were 100-ms, 1000 Hz, 90dB sinusoidal tone bursts. There were three deviant tones, each presented at a probability of 3.3%, which differed from the standard tone on one dimension only: frequency deviant (1500 Hz), intensity deviant (67dB SPL), or duration deviant (50 ms). All mismatch fields, i.e., responses elicited by different deviants, as well as N100m to the standards and deviants, could be explained by neural activity in the supratemporal auditory cortex. The source of N100m to standards and deviants was significantly posterior to the sources for the three different mismatch fields. The mean locations of the equivalent dipoles for the different mismatch fields did not differ significantly from each other, but some differences were found for individual subjects. PMID- 1886962 TI - The effects of channel-selective attention on the mismatch negativity wave elicited by deviant tones. AB - The mismatch negativity (MMN) is an event-related brain potential elicited by infrequent, physically deviant sounds in a sequence of repetitive auditory stimuli. Two dichotic listening experiments that were designed to optimize the selective focusing of attention provided a strong test of Naatanen's proposal that the MMN is unaffected by attention and reflects the operation of a strongly automatic mismatch detection system. In Experiment 1, tones were presented at intervals of 120-320 ms, and the deviant tones (intensity decrements) in both the attended and unattended ears elicited negative waves consistent in waveshape, latency, and distribution with previously described MMNs. In contrast to previous reports, however, the MMN elicited by the unattended-channel deviant was markedly reduced (peak amplitude of less than 1 microV) relative to the corresponding negative wave elicited by the attended-channel deviants (3-4 microV), as well as relative to previously reported MMNs (3-6 microV) elicited by comparable deviations in stimulus intensity. In Experiment 2, which employed interstimulus intervals of 65-205 ms, the unattended-channel MMN elicited by the deviant fainter tones was barely discernible, whereas the corresponding attended-channel negativity was again about 3-4 microV. These findings call into question the assertion that the auditory mismatch detection process and the associated MMN wave are wholly independent of attentional influence. Rather, these data provide evidence that the processing of stimuli in unattended channels can be attenuated or gated at an early sensory level under conditions of highly focused auditory selective attention. PMID- 1886963 TI - Heart rate variability during attention phases in young infants. AB - Heart rate variability during visual attention was studied in infants who were tested cross-sectionally at 14, 20, or 26 weeks of age. They were presented with a recording of a Sesame Street program on a TV screen. After heart rate had decelerated below the prestimulus level and then returned to prestimulus level, a computer-generated pattern replaced the Sesame Street display. Heart rate variability changed throughout attention. The change consisted of a decrease in variability during attention and a return to prestimulus levels approximately five seconds following attention termination. The heart rate and variability responses are consistent with a model of parasympathetic vagal influence on the heart in which vagal firing is increased during sustained attention and is inhibited during attention termination. PMID- 1886964 TI - Behavioral, event-related potential, and EEG/FFT changes at sleep onset. AB - Behavioral, event-related potential (ERP), and EEG measures were obtained to describe more fully the relationship between brain activity and arousal level during the process of falling asleep. In addition to standard polysomnographic measures, tones were presented at random intervals throughout two nights to each of nine subjects. Subjects were instructed to respond to the tones whenever they heard them. Initial sleep onset was disrupted five times following zero through four successive response failures. Sampling of EEG was initiated 5 s prior to tone onset (EEG analyses) and continued for 5 s following tone onset (ERP data). With EEG ordered as a function of response rate, significant increases in power were found across all standard frequency bands for the pretone data at sleep onset. Significant changes in amplitude were related to decreasing responsivity for all late ERP components except P2. Inasmuch as virtually all EEG frequencies and ERP components were strongly influenced by momentary changes in arousal, arousal must be considered a (possibly the) primary determinant of the characteristics of the overall electrical output of the brain. Response cessation coupled with sharp increases in EEG synchronization mark the point of sleep onset. PMID- 1886965 TI - Response inhibition initiates cardiac deceleration: evidence from a sensory-motor compatibility paradigm. AB - Two experiments tested the hypothesis that response selection processes alter the timing of the shift between anticipatory cardiac deceleration and acceleratory recovery. Experiment 1 compared changes in cardiac interbeat interval induced by the manipulation of sensory-motor compatibility in a four choice reaction time task. A direct spatial mapping between a linear array of light-emitting diodes (LEDs) was compared to randomly assigned, indirect (non-compatible) mappings. Experiment 2 repeated these two tasks and added a two choice condition with direct spatial mapping, a task frequently employed to examine heart rate deceleration. Fifteen college aged males participated in Experiment 1; 18 college aged males participated in Experiment 2. In both experiments anticipatory cardiac deceleration either reached a plateau or shifted to acceleration by the interbeat interval in which the stimulus occurred. In contrast to previous reports, a secondary deceleration, rather than cardiac acceleration, often followed the stimulus. The secondary deceleration was greater with non-compatible mapping, slow response speeds, and short intertrial intervals. The findings suggested that the motoric inhibition required during response selection induces a phasic cardiac deceleration. PMID- 1886966 TI - Psychological correlates of nonspecific skin conductance responses. AB - Previous research has indicated that the frequency of skin conductance responses without external stimulation or motor activity is a reliable indicator of psychophysiological states and traits. Some authors have suggested that cognitions elicit nonspecific skin conductance responses. These cognitions may resemble the stimuli that evoke a specific skin conductance response. In a within subjects design (n = 31 graduate students) the onset of nonspecific skin conductance responses triggered a signal for the subject to rate cognitions on several indices. These ratings ("absent" to "fully present") were compared with samples in the absence of phasic electrodermal activity. The subjects' current concerns, negative emotion, subjective arousal, and inner speech were rated to be significantly more intense at the time of nonspecific skin conductance responses compared to electrodermal nonresponding periods. Cognitive processes seem to be concomitants of nonspecific skin conductance responses. PMID- 1886967 TI - What do arithmetic stress tests measure? Protocol variations and cardiovascular responses. AB - Three studies tested the effects of the following design/protocol variations in mental arithmetic: 1) Order of task, 2) vocal versus written delivery of responses, 3) effects of different types of superimposed noise distractors, and 4) varying types of mental arithmetic challenges. All studies used the same basic protocol with 20-min adaptation, 5-min task, and 3-min recovery periods; dependent cardiovascular variables were systolic and diastolic blood pressure and heart rate; in Study 2 respiration rate and respiratory amplitude were also assessed. Findings showed that vocal delivery enhanced subjective distress, lowered performance, and enhanced diastolic blood pressure responses. Noise distraction augmented distress but did not affect task performance. Variable noise distraction augmented systolic blood pressure and heart rate responses but only when math equations were presented on a video screen. Autonomic response adaptation was apparent from first to second tasks but not thereafter. The built in replications strengthened these findings. PMID- 1886968 TI - Depressive delusion. AB - In this study of 160 consecutively admitted inpatients who met ICD-9 criteria of endogenous depression, mood-congruent depressive delusions were ascertained in 14.4% (n = 23). The total HRSD score was significantly higher in the delusional than in the nondelusional group. Delusions of guilt were recorded by far the most frequently. There was a correlation between delusions of guilt in the current depressive episode and suicide attempts in the past. In the delusional patients the individual courses of the illness were characterized by marked symptomatological differences from one depressive episode to another. In all but one of the patients, depressive delusions coincided with a thematically identical experience of anxiety. How often anxiety occurs in delusional form depends substantially on the respective theme of anxiety. In accordance with earlier psychopathological literature the findings confirm that depressive delusion is closely linked to the experience of anxiety. PMID- 1886969 TI - Suicide attitude in breast cancer patients. AB - The suicide attitude in a group of 34 postmastectomy patients was much more marked than in two control groups consisting of 103 medical patients and in 40 healthy subjects, respectively. In a limited sample comprising 23 subjects obtained by excluding the extreme percentile values, certain psychosocial variables (irritability, psychoticism, number of confidants, number of persons in the same household) were observed to be significantly associated with the suicide attitude in postmastectomy patients. On the other hand, no differences were evident, both regarding the interval of time following initial diagnosis and between married and single patients. PMID- 1886970 TI - The psychopathology of suicide in the north western Peloponnesus. AB - A postmortem inquiry of 105 legal documents concerning suicide deaths obtained from the Office of the District Attorney covering the province of Achaia was studied for the 15-year period 1970-1984. The suicides were classified into two groups; group A consisting of 63 suicides (with a history of psychiatric illness) and group B consisting of 42 suicides (with no history of psychiatric disturbance). The findings suggest that people with a history of psychiatric illness committing suicide are disorganized in their personal and social life, with frequent previous suicidal attempts. Whereas, the nonpsychiatrically diagnosed group seemed to commit suicide under outside pressures which dislocated their lives progressively or abruptly. The differences between the two suicide groups are discussed and compared with similar studies regarding suicidal behavior. PMID- 1886971 TI - Speech characteristics in depression. AB - This study examined the relationship between speech characteristics and psychopathology throughout the course of affective disturbances. Our sample comprised 20 depressive, hospitalized patients who had been selected according to the following criteria: (1) first admission; (2) long-term patient; (3) early entry into study; (4) late entry into study; (5) low scorer; (6) high scorer, and (7) distinct retarded-depressive symptomatology. Since our principal goal was to model the course of affective disturbances in terms of speech parameters, a total of 6 repeated measurements had been carried out over a 2-week period, including 3 different psychopathological instruments and speech recordings from automatic speech as well as from reading out loud. It turned out that neither applicability nor efficiency of single-parameter models depend in any way on the given, clinically defined subgroups. On the other hand, however, no significant differences between the clinically defined subgroups showed up with regard to basic speech parameters, except for the fact that low scorers seemed to take their time when producing utterances (this in contrast to all other patients who, on the average, had a considerably shorter recording time). As to the relationship between psychopathology and speech parameters over time, we found significant correlations: (1) in 60% of cases between the apathic syndrome and energy/dynamics; (2) in 50% of cases between the retarded-depressive syndrome and energy/dynamics; (3) in 45% of cases between the apathic syndrome and mean vocal pitch, and (4) in 71% of low scores between the somatic-depressive syndrome and time duration of pauses. All in all, single parameter models turned out to cover only specific aspects of the individual courses of affective disturbances, thus speaking against a simple approach which applies in general. PMID- 1886972 TI - [Concepts of depressive patients regarding the cause of their disease]. AB - In 60 patients suffering from either neurotic or endogenous depression (according to ICD-9), the aetiological concepts regarding their illness were studied by means of content analysis of answers to an interview question. Most patients had multifactorial aetiological concepts. Psychosocial concepts were more frequent than biological ones; this bias, however, was less pronounced in endogenous depressives (and, within this group, in bipolar vs. unipolar patients) than in neurotic depressives. The latter stressed triggering events as causes of illness, whereas for endogenous depressives, dispositions were more important. A positive expectancy of being able to influence the illness correlated with an aetiological model which implied triggering as well as predisposing factors. PMID- 1886973 TI - [Using the condom--on coping with a necessary evil]. AB - Social aspects of condom use are mentioned by outlining some sections of the historical development of condom use (early and pre-history, family history in England during the 19th century, combat against syphilis, the "birth-strike debate" in the German social democratic party). A few results of an own questionnaire research about students' sexuality (n = 666) are presented. They give some hints about a change in the use of different contraceptional techniques in comparison with former studies done in the sixties and at the beginning of the eighties. Condom users and non-users seem to be different in terms of concepts of partnership, sexual contentment and aids preventive behaviour. Finally we discuss some psychological aspects of condom use with regard to the--sparse--relevant literature and to an own qualitative study of the motivation of users and non users. PMID- 1886974 TI - [Theory and methods of clinical assessment of defense mechanisms]. AB - Originally, defense theories had been developed as metapsychological categories. Applied to empirical investigations, however, defense theories have to be adapted to the specific empirical design. A clinical and an empirical theory on defense, for which the same terms are often used, are by no means identical. The clinical and empirical terms have to be matched. An empirical theory on defense should correspond not only to metapsychological categories but be adequate for the research object. Among the most common empirical procedures, clinical ratings of defense mechanisms come closest to clinical judgements, but entail methodological problems. Group ratings underly dynamic group processes which are difficult to control and thus imply a risk. The advantage of such a rating, however, is that affective processes within the rating team may be seen as an extended observational instrument. Despite their methodological restrictions, consensus ratings may be seen as an instrument the further development of which is worthwhile. PMID- 1886975 TI - [Origin of problematic constellations in psychiatric family care. Theoretical considerations and presentation of the course of a discontinued family care episode]. AB - Psychiatric family care is a therapeutic environment for mentally ill long-term patients that pays particular attention to the individuality of the patient, contrary to the hospitalising psychiatric clinic. The influence exercised by the host family on the positive development of the integration process is undisputed in literature, but has been hardly investigated so far in respect of its actual contents. Those who are practically engaged in family care have been discussing for some time whether successful integration is effected by "good host families" or by the special constellation that develops between the host family and the guest. The present article tries to emphasise (following a review of the literature) on the basis of a discontinued family care episode that integration into a host family is not a static affair but a highly sensitive process determined by the biography of the guest and the integration between host family and guest (or guests). The possible consequences for the care process are discussed. PMID- 1886977 TI - A generalized concept for cell killing by heat. Effect of chronically induced thermotolerance. AB - Chronic thermotolerance was induced in Chinese hamster ovary (CHO) cells by pretreatment at 40 degrees C for various times ranging from 15 min to 16 h. The thermotolerant cells were either exposed to single heat treatments at 43 degrees C or subjected to step-down heating consisting of a priming treatment at 43 degrees C for 90 min followed immediately by a graded test treatment at 40 degrees C. Data evaluation using a mathematical model published previously (H. Jung, Radiat. Res. 106, 56-72, 1986) showed that the rate constants p for the production of nonlethal lesions at 43 and 40 degrees C decreased by a factor of 20 with the duration of the thermotolerance-inducing pretreatment at 40 degrees C and approached exponentially (half-time 1.24 +/- 0.11 h) a minimum value. By contrast, the rate constants c for the conversion of nonlethal lesions into lethal events were not altered by the induction of thermotolerance; this applied to both c (43 degrees C) and c (40 degrees C). After transferring thermotolerant cells (pretreatment at 40 degrees C for 3 h) to 37 degrees C, the rate constants p increased exponentially with time (doubling time 25 +/- 5 h). Similar kinetics for the development and decay of chronic thermotolerance was shown to be applicable also to extended heating at 40 degrees C and to various data from the literature. PMID- 1886976 TI - [Emotional status and immunoglobulin A in saliva--review of the literature]. AB - Salivary immunoglobulin A, secreted by the local secretory immune system of the upper respiratory tract, plays an important role in the protection of infections. Psychoneuroimmunological studies postulating influences of mood states on secretion of immunoglobulin A are reviewed and discussed with regard to their internal and external validity. The results on the influence of emotional stress are heterogeneous: Lower, as well as higher, as well as unchanged secretions of salivary immunoglobulin A have been reported. This may be due to insufficient control of intervening variables, to different methodologies and to selection of non-representative subject populations, so that the relationship between emotional stress and secretion of salivary immunoglobulin A remains still under discussion. On the other side, two studies indicate that mental relaxation procedures can lead to increased secretions of salivary immunoglobulin A in comparison to vigilance task, finger touching or no explicit treatment. However, more research is required, especially on the size and duration of the induced effect. Future psychoneuroimmunological research strategies should consider to a greater extend emotion-specific and person-specific aspects, methods used in experimental virology and mediators between mood and salivary immunoglobulin A. PMID- 1886978 TI - Dose dependence of the oxygen enhancement ratio (OER) in radiation inactivation of Chinese hamster V79-171 cells. AB - The dose dependence of the oxygen enhancement ratio (OER) has been examined through multiple measurements of the response of Chinese hamster V79-171 cells to low and high doses of radiation under aerobic and hypoxic conditions. In this series of experiments the cells were maintained at 37 degrees C throughout the gassing and irradiation periods, to simulate normal physiological conditions. Flow cytometry and cell sorting techniques were used to facilitate accurate measurement of cell survival throughout the dose range, but particularly at low dose. The OER was found to decrease significantly at low dose, qualitatively confirming earlier reports from this laboratory, though the decrease was somewhat smaller in the present series. This difference may be a temperature effect since in the earlier experiments irradiation was at 0 degree C. This report shows that the OER decreases from a value of 2.87 +/- 0.16 (standard deviation of mean) at S = 0.01 to 2.36 +/- 0.19 at S = 0.80. Both alpha and beta are altered by the presence of oxygen. The OER is presented as a function of dose in nitrogen. PMID- 1886979 TI - The radiation response of asynchronous cells at low dose: evidence of substructure. AB - Flow cytometry and cell sorting techniques have been used together with repeated measurement in an attempt to define better the radiation survival response of asynchronously dividing Chinese hamster V79-171 cells under aerobic and hypoxic conditions. Although the first two decades of cell inactivation have been examined, particular attention has been given to the low-dose range of a few grays, as used in individual radiation therapy treatments. A single linear quadratic dose-response function was consistently unable to fit both the low-dose and high-dose data satisfactorily, suggesting a two-component response. Separate fitting of the low-dose and high-dose portions of the response yielded alpha and beta values which differed significantly (P = 0.001 to 0.002). The data are consistent with the hypothesis that the observed substructure simply reflects the presence of subpopulations of sensitive (G1-, G2-phase) and resistant (late S phase) cells, which are resolved in these measurements. These results may have significance for certain situations in radiation therapy and in biophysical modeling of the radiation response. PMID- 1886980 TI - Caffeine sensitization of Chinese hamster ovary cells to heat killing. AB - The effects of the methylxanthine, caffeine, on heat sensitization was investigated using Chinese hamster ovary (CHO) cells. Caffeine sensitized CHO cells to heat killing by reducing both the shoulder and the slope of the 44 degrees C survival curve. Heating was performed in suspension by addition of cells to preheated spinner flasks containing caffeine. Changes in intracellular free calcium levels, [Ca2+]i, were measured at 37 degrees C using the luminescent probe aequorin. Caffeine (1-5 mM) induced a transient increase in [Ca2+]i at 37 degrees C. The transient increase in [Ca2+]i was reduced 15-fold when 5 mM caffeine was added to aequorin-loaded cells suspended in Ca(2+)-free Hanks' balanced salt solution. However, 5 mM caffeine sensitized the cells to the same extent when they were suspended in either Ca(2+)-containing or Ca(2+)-free Hanks' balanced salt solution. The mechanism of heat sensitization by caffeine is still unknown. PMID- 1886981 TI - Effects of calcium buffering on the synthesis of the 26-kDa heat-shock protein family. AB - We have reported on the effect of heat in C127 cells having various basal levels of the Ca(2+)-binding proteins calmodulin (CaM) or parvalbumin [Evans, Simonette, Rasmussen, Means, and Tomasovic, J. Cell. Physiol. 142, 615-627 (1990)]. These studies suggested that induction of the synthesis of 26-kDa heat-shock protein (hsp-26) depended on increased intracellular free Ca2+ [Ca2+]i and that induction was abrogated by increased Ca(2+)-binding capacity. To evaluate further the role of [Ca2+]i in mediating the response to hyperthermia and the potential for Ca(2+) buffering to affect these processes, we loaded C127 parental cells with the Ca2+ chelators BAPTA or quin-2 (5 microM for 60 min) and then immediately heated the cells (30 min at 43 degrees C) and labeled them (3 h at 37 degrees C) with [3H]leucine. Measurements of [Ca2+]i with quin-2 and fura-2 showed that an increase in [Ca2+]i occurred with this heat dose, but that the quin-2 buffered that increase. Two-dimensional gels showed that cells loaded with BAPTA and quin 2 had a reduced rate of synthesis of the most basic (nonphosphorylated) hsp-26a isoform. The apparent synthesis of the more acidic isoforms (hsp-26b, hsp-26c) was less affected, but labeling studies with 32P showed this reflected continued accumulation of these phosphorylated isoforms, especially the most highly phosphorylated hsp-26c. Although it reduced hsp-26a synthesis, the temporary buffering of [Ca2+]i did not alter the subsequent expression of heat killing or the extent of thermotolerance significantly, possibly because phosphorylated hsp 26 was still generated. These data support the hypothesis that perturbations of [Ca2+]i directly modulate induction of hsp-26a synthesis. PMID- 1886982 TI - Changes in the nuclear structure in the radiation-sensitive CHO mutant cell, xrs 5. AB - The structural organization of the cell nucleus was investigated by transmission electron microscopy in the radiosensitive Chinese hamster ovary (CHO) cell mutant, xrs-5 (D0 = 45 cGy), relative to parental K1 cells (D0 = 200 cGy). In 99% of all xrs-5 cells, the outer layer of the nuclear envelope was separated from the inner layer, while 96% of K1 cells had closely apposed layers. This separation of the inner and outer layers of the nuclear envelope in xrs-5 cells was not explained by an increased susceptibility of xrs-5 cells to osmotically induced changes because (1) xrs-5 cells retained the altered nuclear periphery even when several different fixation protocols were used and (2) xrs-5 cells were not more susceptible to cell lysis as measured by trypan blue dye exclusion or by the extracellular presence of lactate dehydrogenase. The difference in the morphological organization in the nuclear periphery of xrs-5 cells correlated with the radiation sensitivity of the cells; xrs-5 cells which spontaneously reverted to a radiation sensitivity similar to that of K1 cells also reverted to a nuclear morphology similar to that of K1 cells. The inner and outer layers of the nuclear envelope were retained in nuclear scaffolds isolated from K1 and xrs 5 cells, indicating that components of the nuclear periphery are part of the nuclear scaffold. These data show that xrs-5 cells have an altered nuclear periphery which correlates with the radiation sensitivity of the cells. The separation of the layers of the nuclear envelope may represent an altered template for repair of DNA damage at the nuclear scaffold and thus may play a role in the defective repair of X-ray-induced DNA double-strand breaks in xrs-5 cells. PMID- 1886983 TI - Regulation of murine megakaryocyte size and ploidy by non-platelet-dependent mechanisms in radiation-induced megakaryocytopenia. AB - Megakaryocytic macrocytosis was evaluated in mice after irradiation with 6.5 Gy 60Co gamma rays. During the second and third months after sublethal irradiation, one or more of the following abnormalities of thrombocytopoiesis was present: thrombocytopenia, megakaryocytopenia, macromegakaryocytosis, a shift to higher ploidies, and enlargement of cells within ploidy groups. After transfusion induced thrombocytosis, reductions in megakaryocyte size were delayed or absent relative to non-irradiated mice, and there was more of a tendency to shift to lower values for megakaryocyte ploidy. Mice with radiation-induced megakaryocytopenia failed to show rebound thrombocytosis during recovery from immunothrombocytopenia, in spite of further increases in megakaryocyte size and ploidy. The findings support the hypotheses that numbers of megakaryocytes may influence the regulation of megakaryocytopoiesis even when there is an excess of platelets and that ploidy distribution is not the sole determinant of the average size of a population of megakaryocytes. After irradiation, persistent megakaryocytopenia may not severely affect platelet production under steady-state conditions, but the ability of the marrow to respond to homeostatic regulation is compromised. PMID- 1886984 TI - Novobiocin treatment reverses radiation-induced alterations in higher-order DNA structure in L5178Y nucleoids. AB - We have studied the effect of novobiocin treatment on radiation-induced damage and its repair in higher-order DNA structure in two mouse leukemia cell lines differing in their radiosensitivity, L5178Y-R (LY-R) and L5178Y-S (LY-S). We used the fluorescent halo technique to measure alterations in the superhelical density and the topological constraints of DNA in LY-R and LY-S nucleoids. The results for untreated cells show that both cell lines reached maximal DNA unwinding at the same concentration of propidium iodide (PI), whereas LY-S nucleoids were less efficient in their ability to rewind their DNA. The loop size did not differ significantly between the cell lines. Incubation of LY-R and LY-S cells with novobiocin at a concentration which does not influence survival (0.1 mM for 45 min), but inhibits DNA synthesis in LY-R cells (by 28%) to a greater extent than in LY-S cells (by 10%), also causes more DNA unwinding in LY-R nucleoids than in LY-S nucleoids. However, a decreased superhelical density was observed in nucleoids from both cell lines. Novobiocin applied before, and present during, irradiation prevents radiation-induced alterations in DNA supercoiling more efficiently in LY-R than in LY-S cells. The presence of novobiocin during the repair period increased DNA rewinding to levels not significantly different from control values in nucleoids from both cell lines. PMID- 1886985 TI - Prostanoid antagonists inhibit the response of the microcirculation to "early" photodynamic therapy. AB - Microcirculatory shutdown appears to be of central importance in the mechanisms of action of photodynamic therapy (PDT). Traditionally 24-48 h are allowed between the administration of the photosensitizer and light to allow for tumor localization. However, previous studies have shown that the effects of PDT on the microcirculation are maximal soon after administration of the photosensitizer when serum levels are highest. This study involved the use of television video microscopy of the cremaster muscle microcirculation of male Sprague-Dawley rats to study the involvement of prostanoids in the effects of PDT on the microcirculation 30 min after administration of photofrin II. Pretreatment with topical indomethacin resulted in an altered response to PDT with arteriolar dilation and delay in vessel shutdown. The thromboxane A2 antagonist SQ29548 (100 mg/kg/min iv) resulted in a significant delay in platelet thrombus formation in arterioles and venules. These results indicate that prostanoids are involved in the mediation of the response of the normal microcirculation to PDT. PMID- 1886986 TI - Oxygen enhancement ratio as a function of dose and cell cycle phase for radiation resistant and sensitive CHO cells. AB - There is still controversy over whether the oxygen enhancement ratio (OER) varies as a function of dose and cell cycle phase. In the present study, the OER has been measured as a function of survival level and cell cycle phase using volume flow cell sorting. This method allows both the separation of cells in different stages of the cycle from an asynchronously growing population, and the precise plating of cells for accurate measurements at high survival levels. We have developed a cell suspension gassing and sampling system which maintained an oxygen tension less than 20 ppm throughout a series of sequential radiation doses. For both radiation-resistant cells (CHO-K1) and a radiation-sensitive clone (CHO-xrs6), we could separate relatively pure populations of G1-phase, G1/S boundary, S-, and G2-phase cells. Each cell line showed a typical age response, with cells at the G1/S-phase boundary being 4 (CHO-K1) to 12 (CHO-xrs6) times more sensitive than cells in the late S phase. For both cell lines, G1-phase cells had an OER of 2.3-2.4, compared to an OER of 2.8-2.9 for S-phase and 2.6 2.7 for G2-phase cells. None of these age fractions showed a dependence of OER on survival level. Asynchronously growing cells or cells at the G1/S-phase boundary had an OER similar to that of G1-phase cells at high survival levels, but the OER increased with decreasing survival level to a value near that of S-phase cells. These results suggest that the decrease in OER at high survival levels for asynchronous cells may be due to differences in the OERs of the inherent cell age subpopulations. For cells in one cell cycle stage, oxygen appears to have a purely dose-modifying effect. PMID- 1886987 TI - Apoptosis in irradiated murine tumors. AB - Early radiation responses of transplantable murine ovarian (OCaI) and hepatocellular (HCaI) carcinomas were examined at 6, 24, 48, 96, and 144 h after single photon doses of 25, 35, or 45 Gy. Previous studies using tumor growth delay and tumor radiocurability assays had shown OCaI tumors to be relatively radiosensitive and HCaI tumors to be radioresistant. At 6 h, approximately 20% of nuclei in OCaI tumors showed aberrations characteristic of cell death by apoptosis. This contrasted to an incidence of 3% in HCaI tumors. Mitotic activity was eliminated in OCaI tumors but was only transiently suppressed in HCaI tumors. At 24-96 h, OCaI tumors continued to display apoptosis and progressive necrosis, whereas HCaI tumors responded by exhibiting marked pleomorphism. Factors other than mitotic activity may influence tumor radiosensitivity, and one of these may be susceptibility to induction of apoptosis (programmed cell death), because this was a prominent early radiation response by the radiosensitive OCaI tumors. PMID- 1886988 TI - Effects of some nonsteroidal anti-inflammatory agents on experimental radiation pneumonitis. AB - Corticosteroids have previously been found to be protective against the mortality of radiation pneumonitis in mice, even when given well after lethal lung irradiation. We explored the possibility that this effect was due to their well known anti-inflammatory actions by giving various nonsteroidal inhibitors of arachidonate metabolism to groups of mice that had received 19 Gy to the thorax (bilaterally). Treatments of four cyclooxygenase inhibitors, one lipoxygenase inhibitor, and one leukotriene receptor antagonist, given by various routes in various doses, were commenced 10 weeks after irradiation or sham irradiation and continued throughout the period when death from radiation pneumonitis occurs, 11 26 weeks after irradiation. Each of the treatments had the appropriate effect on arachidonate metabolism in the lungs as assessed by LTB4 and PGE2 levels in lung lavage fluid. The principal end point was mortality. The 5-lipoxygenase inhibitor diethylcarbamazine and the LTD4/LTE4 receptor antagonist LY 171883 markedly reduced mortality in dose-response fashion. The effects of cyclooxygenase inhibitors were divergent; piroxicam and ibuprofen were marginally protective, indomethacin in all doses accelerated mortality, and aspirin reduced mortality in a dose-response fashion. These results suggest that the protective effect of corticosteroids in radiation pneumonitis can be tentatively attributed to their anti-inflammatory actions, and that nonsteroidal anti-inflammatory agents, particularly those that affect lipoxygenase products, may offer equal or better protection than corticosteroids against mortality due to radiation pneumonitis. PMID- 1886989 TI - Differences in thermotolerance induced by heat or sodium arsenite: correlation between redistribution of a 26-kDa protein and development of protein synthesis independent thermotolerance in CHO cells. AB - In previous studies, we have demonstrated the differences in thermotolerance induced by heat and sodium arsenite (Lee et al., Radiat. Res. 121, 295-303, 1990). In this study, we investigated whether a 26-kDa protein might play an important role in evincing these differences. Chinese hamster ovary (CHO) cells treated for either 1 h with 100 microM sodium arsenite (ARS) or 10 min at 45.5 degrees C became thermotolerant to a test heat treatment at 43 degrees C administered 6 or 12 h later, respectively. After the test heating at 43 degrees C for 1.5 h, the level of 26-kDa protein in the nucleus was decreased by 92% in nonthermotolerant cells, 78% in ARS-induced thermotolerant cells, and 3% in heat induced thermotolerant cells. Inhibiting protein synthesis with cycloheximide (CHM, 10 micrograms/ml) after ARS treatment eliminated thermotolerance to 43 degrees C and delayed restoration of the 26-kDa protein in the nucleus. In contrast, CHM neither prevented the development of thermotolerance nor inhibited the restoration of the 26-kDa protein in heat-induced thermotolerant cells. However, when cells were exposed to cold (4 degrees C), immediately after initial heating, restoration of the 26-kDa protein and development of thermotolerance did not occur. These results demonstrate a good correlation between the restoration and/or the presence of this 26-kDa protein and the development of protein synthesis-independent thermotolerance. PMID- 1886990 TI - Prolonged hyperthermia eliminates mycoplasma from cultured human and rat brain tumor cell lines. AB - Mycoplasma infection of mammalian cells in culture is a common occurrence that can affect the results of experimental protocols. Current methods of eliminating mycoplasma from cell cultures are usually tedious, time-consuming, and sometimes unsuccessful. In the present study, four cultured brain tumor cell lines (human U 251 MG, U-87 MG, SF-126, and rat 9L) were heavily contaminated with Mycoplasma orale. Heating the cultures to 41 degrees C for at least 96 h eliminated the contamination for up to 7 months, the maximum period of observation. The time chosen to assay for the presence of mycoplasma in cultures was critical: in some cultures heated for less than 96 h that initially appeared to be free of contamination, mycoplasma began to appear after 2 weeks. Heat-treated cells grew at the same rate as unheated control cells. Infected cells were more sensitive to X rays than uncontaminated cells, but the sensitivity reverted to normal after mycoplasma was eliminated by hyperthermia. The heating method does not require a cell cloning procedure or the use of exogenous materials. Treated cell cultures exhibit normal growth and radiation sensitivity, and the technique seems to be reliable and efficient. PMID- 1886991 TI - Evidence against enhancement of the radioresistance of Escherichia coli by cloned Deinococcus radiodurans DNA. AB - Deinococcus radiodurans genomic DNA, introduced to Escherichia coli in cloning vectors, has been reported to produce radioresistant E. coli that can be selected by gamma irradiation. In this report prior results are reassessed experimentally, and additional studies are presented. Results to date suggest that the acquired radioresistance of E. coli selected by gamma irradiation does not stem from expression of stable plasmid-encoded D. radiodurans sequences, and that acquired radioresistance is not readily transmitted to naive (unirradiated) E. coli by transformation of plasmid recovered from the radioresistant isolates. Several interpretations are discussed. PMID- 1886992 TI - [The level of lymphocytes in the peripheral blood as a criterion of the degree of severity of acute radiation sickness (based on materials from the accident at the Chernobyl Nuclear Power Station)]. AB - A study was made of the peripheral blood lymphocyte level as a function of gamma radiation dose after single gamma-radiation attack resulted from Chernobyl disaster. After the initial drop an average level of lymphocytes was stabilized by day 2 after exposure and no further systematic decrease in the number of lymphocytes occurred. The accuracy of prognostication of the severity of acute radiation sickness, determined by the average lymphocyte level on days 3-6 amounted to as low as 50%. However, when the neighbouring, by the severity, groups of patients were taken into account, the accuracy was 88%. PMID- 1886993 TI - [The status of the endocrine function of the thymus in acute radiation sickness resulting from the accident at the Chernobyl Nuclear Power Station]. AB - Data are presented on the role of inhibition of endocrine function of the thymus in the pathogenesis of acute radiation sickness resulted from the direct and indirect (via the increased glucocorticoid production) effects of ionizing radiation. The complex treatment, including nonspecific active immunotherapy, permitted to normalize the thymic hormone level and certain parameters of the immune system. PMID- 1886994 TI - [A comparative evaluation of the genetic effects of uniform internal (137Cs) and local x-ray (testes) irradiation of rats]. AB - In experiments with rats it was shown that with equal absorbed doses after single injection of 137Cs and local X-irradiation of testes the mutation yield in gametes was different when tested by the frequency of dominant lethals and half lethals, reciprocal translocations, univalents, and chromosome fragments. A higher efficiency of whole-body irradiation as compared to local exposure of testes, with respect to genetic damages induction, and the statistically significant increase in the number of the damages during a long period of time after cessation of the absorbed dose formation indicated that indirect effects of whole-body irradiation contributed to the injury to hereditary structures and permitted to estimate approximately their contribution (up to 50%). PMID- 1886995 TI - [The biological action of low-level radiation]. AB - On the basis of their own data and the literature the authors have analyzed the mechanism of biological action of low-level radiation on cells. In studying the harmful effect of gamma-radiation (10-40 cGy) on HeLa cells it was shown that damages occurred in 12 postirradiation generations. Analysis of cell distribution within the colonies has demonstrated that the share of colonies with low cell content and the number of giant cell increase. These data indicate that low-level radiation causes reproductive cell death that can occur not immediately but in later generations. PMID- 1886996 TI - [The effect of low doses of x-rays on the biochemical processes in the brain and on urinary metabolites in fasted rats]. AB - The effect of mild doses of X-rays (three fractions, each of 100 R) on energy metabolism of the brain of starved rats has been investigated. It is inferred that X-radiation may cause serious detrimental changes of enzymes involved in glucose metabolism (glucose-6-phosphate dehydrogenase and fructose diphosphate aldolase) and in peroxidation (of catalase and lipid peroxidase), and of the acetylcholine activity which is determined by the cholinesterase level. Dynamics of changes in the protein and nucleic acid content of the brain has been studied. It has been shown that the level of 4-HIAA and 3M4HMA in the brain increases after irradiation of starved and normally fed rats. PMID- 1886997 TI - [The effect of low doses of ionizing radiation on the intermediate filaments and the Ca2+-activated proteolysis system in the rat brain]. AB - The immunochemical methods were used to study the effect of low-level radiation (0.00645 C/kg and 0.0129 C/kg) on the content and polypeptide composition of glial intermediate filament proteins (GIFP) in different rat brain areas. Changes in glial fibrillar acidic protein (GFAP) concentration were more significant with the dose of 0.0129 C/kg than 0.00645 C/kg. It is suggested that soluble GIFP is more susceptible to the effect of Ca(2+)-dependent proteinases, calpains, than the filament one is, and degrades as early as the first few hours following irradiation. However, low radiation doses were ineffective with respect to calpains activity in the animal brain. The increased Ca2+ concentration enhances considerably GFAP degradation under the effect of calpains I and II. It is suggested that with low radiation doses the rearrangements of glial intermediate filaments may occur due to activation of calpains by releasing Ca ions. PMID- 1886998 TI - [The effect of low-dose whole-body gamma-irradiation on the activity of enzyme systems in the rat adrenal medulla]. AB - A study was made of the pattern of changes in histochemical indices of key enzymes of the tricarboxylic acid cycle (succinate dehydrogenase) and glycolysis (lactate dehydrogenase) as well as of catecholamines (monoamine oxidase) in cells of the adrenal medulla of young and adult albino rats subjected to external whole body gamma-irradiation with doses of 0.5 and 1.0 Gy (dose-rate of 2.7 X 10(-4) Gy/s). Radiosensitivity of the enzyme systems under study in the adrenal gland cells of young animals was higher than in that of adults. Changes of their levels in different periods of observation were mainly of phase nature and indicated the development of adaptation syndrome in the animal organism. PMID- 1886999 TI - [The occurrence of hormesis during gamma-irradiation of developing rat pups]. AB - Development of rat pups was shown to accelerate (body mass made up 121% of control) after gamma-irradiation on day 21 of the postnatal development (2.88 cGy, dose-rate of 0.12 cGy/h). Higher cumulative doses (14.4 and 144 cGy) did not influence the body mass growth, and inhibition was only caused by doses exceeding 150 cGy. PMID- 1887000 TI - [Phospholipid metabolism in lymphoid cells at long-term periods following sublethal gamma-irradiation of rats]. AB - Dynamics of phospholipid metabolism in rat thymocytes and bone marrow cells was studied 1-6 months after fractionated irradiation. The rate of total and individual lipid synthesis was shown to increase in the exposed cells. The rate of lipid synthesis increased 1 and 2 months after irradiation and was normalized 3 and 6 months after irradiation. PMID- 1887001 TI - [Impairment of immunity and long-term effects of 239Pu in rats]. PMID- 1887002 TI - [The effect of gamma-irradiation on the level of circulating immune complexes in rat blood]. AB - During the first 10-20 min after gamma-irradiation (75 Gy) of rat head in the cranio-caudal direction a drastic 2-3-fold decrease was observed in the level of circulating immune complexes (CIC) in the blood. CIC content of the blood was restored 60 min after irradiation, and no changes occurred during the following 5 hour period of observation. PMID- 1887003 TI - [The effect of ionizing radiation and immunomodulators on the development of the graft versus host reaction]. AB - The reaction "transplant against host" (RTAH) was performed by subcutaneous transplantation of popliteal lymphnode lymphocytes of C57Bl/6 mice (CBA X C57Bl/6)F1 mice. gamma-Irradiation of donors with a dose of 6 Gy was shown to activate the function of T-lymphocytes, effectors in RTAH. Recipients irradiated with the same dose exhibited a drastic decrease in the ability of the organism to restrict RTAH. Decaris administered 15 min after irradiation of donors removed the postirradiation RTAH increase. In nonirradiated donors or recipients, the immunomodulators increased RTAH. PMID- 1887004 TI - [The effect of in vitro X-irradiated blood transfusions on the morphostructure of immunocompetent organs and their nerve elements]. AB - A study was made of changes that occur in the rat thymus, spleen, lymph nodes, their nerve elements, and spinal ganglia under the effect of the in vitro X irradiated blood transfusions. Parallelism was noted in the activation of the immunocompetent organ morphostructures, the rate of reactive alterations in nerve elements, and the improvement of the immunity indices. PMID- 1887005 TI - [The effect of irradiation on the growth of human laryngeal tumors transplanted under the kidney capsule of immunocompetent mice]. AB - A study was made of the influence of gamma-radiation on the growth of human larynx squamous cell carcinoma transplanted under the capsule of the kidney of immunocompetent mice. The transplants were shown to increase in size 6 days after transplantation. Irradiation of animals 24 h after transplantation inhibited considerably the tumor growth. However, the preirradiation (24 h before operation) inhibited the growth of nonirradiated transplants to the same extent as the exposure of mice with the transplanted tumor fragments did: the radiation dose that induced 50% inhibition of the growth was 4.5 Gy and 5.3 Gy, respectively. Preliminary data indicate that tumor fragment of patients with the unfavourable prognosis increase in size and respond to radiation to a lesser extent. PMID- 1887006 TI - [The granulocyte-macrophage colony stimulating factor and the radiation protective effect of yeast mannan]. AB - The effect of mannan polysaccharide on the haemopoiesis recovery in irradiated mice has been investigated. Mannan has been shown to exert both the protective and the stimulatory effect: it accelerates restoration of femur bone marrow cellularity and nucleate cell number in the peripheral blood and causes a larger initial yield and subsequent more rapid postirradiation dynamics of pluripotent haemopoietic stem cells and precursor cells of granulocytes and macrophages. PMID- 1887007 TI - [The effect of myelopid on antibody formation in gamma-irradiated animals]. AB - The effect of a new immunocorrecting preparation, Myelopid, on the antibody forming cell content of mouse spleen after gamma-irradiation (1-3 Gy) has been investigated. The preparation administered after immunization of mice with sheep erythrocytes increases the number of antibody-forming cells in the spleen, the effect being a function of radiation dose and time interval between the exposure and immunization. The preparation is ineffective when delivered after irradiation, but prior to immunization. PMID- 1887008 TI - [The radioprotective effect of extracts of Archangelica officinalis Hoffm. and Ledum palustre L. on mice]. AB - A single injection of Archangelica officinalis Hoffm. and Ledum palustre L. extracts to mice 5-15 min before irradiation with a median lethal dose increased their survival rate. The most favourable effect was produced by a combination of the two preparations: by day 30 100% of animals survived after a dose of 6 Gy (LD50/30); 70% survived after a dose of 7.5 Gy (LD90/30), and 25% after a dose of 8 Gy (LD100/12). DMF for the extract mixture was 1.48. PMID- 1887009 TI - [The effect of electromagnetic waves in the millimeter wave range on the bioenergetic processes in the liver and stomach during experimental injuries to the stomach]. PMID- 1887011 TI - [The triboluminescent spectra of the blood of gamma-irradiated rats]. AB - Triboluminescence (TL) of rat blood 3 h after whole-body single exposure to gamma radiation (0.25, 1, 3, and 5 Gy) exhibited positive coefficient of correlation r = 0.99 (at a wave length of 412 nm) with radiation dose. The effect of ionizing radiation on the animal body caused changes in blood TL within the fixed areas of the spectral range, whose fluctuation parameters were conditioned by specifically significant radiobiological changes and nonspecific adaptive reactions. PMID- 1887010 TI - [The dose-response relationship for indices of the micronucleus test using neutron-spectra therapeutic irradiation]. AB - It was shown by method of cytokinetic blocking that with neutron irradiation of human lymphocyte culture (mean energy of 0.85 MeV, doses of 0.05 to 2 Gy) the dose-response relationship, with respect to the share of binuclear cells with micronuclei and the frequency of micronuclei in binuclear cells, was of a multiphase nature with a more or less manifest plateau within the dose-range from 0.5 to 1.0 Gy. Both micronuclear tests may be used for indicating the degree of radiation injury to the organism caused by neutrons of the above-mentioned energy and doses of 0.05-0.5 Gy. PMID- 1887012 TI - [The intensity of proteolysis in the peripheral blood lymphocytes of rats in the early period of acute radiation injury]. AB - Comparative analysis of biochemical indices that reflect the proteolysis rate in rat peripheral blood lymphocytes in normal conditions and during the first 4-6 h after whole-body single uniform gamma-irradiation with lethal (7.5 Gy) and nonlethal (3 Gy) doses has revealed that the pronounced activation of proteolysis in lymphocytes and the disturbances in the inhibitor/protease balance are characteristic of the severe form of radiation damage with fatal outcome. Simultaneously changes occur in biochemical indices of plasma that reflect a catabolic pathway of metabolism in the whole-body. The absence of similar changes in the blood of the survived animals permits to recommend the biochemical indices under study to be used for early prognosis of the radiation affection outcome. PMID- 1887013 TI - [Radiation-induced changes in the content of squalene, lathosterol and cholesterol in rat blood proteins]. AB - Normal and irradiated fibrinogen, gamma-globulins, alpha- and beta-globulins and albumins of blood plasma were shown to contain squalene, lathosterol, cholesterol and some other compounds as lipid components. Radiation alteration of the total number of unsaponifiable substances and some lipid components in the individual blood plasma proteins followed certain regularities depending on the kind of a protein. The level of radiation changes in the content of lipid components in specific proteins of blood plasma was shown to be a function of radiation dose and time after irradiation. PMID- 1887015 TI - [Conclusions of the Commission on the ecological situation in the vicinity of the enterprise Mayak of the USSR Minatomenergoprom that was organized by the Presidium of the USSR Academy of Sciences No. 1140-501, June 12, 1990]. PMID- 1887014 TI - [Modification of the chronotropic-inotropic relations in the atrial and ventricular myocardium during external gamma-irradiation]. AB - It has been shown of isolated muscle preparations of rat heart that external gamma-irradiation with a dose of 6 Gy reduces the contractile capacity of myocardium and changes the chronoinotropic relationships: in the auricle, the rate/power relationship and the potentiating effect of the passive interval increase, and in the ventricles, the potentiating effect decreases. Modification of the chronoinotropic relationships may be associated with changes in the calcium ion transport in the heart cells. PMID- 1887016 TI - Fetal ventricle: importance in routine obstetric sonography. PMID- 1887017 TI - Invasion of the neurovascular bundle by prostate cancer: evaluation with MR imaging. AB - Preservation of the neurovascular bundle (NVB) and potency without compromising tumor control are current objectives of radical retropubic prostatectomy as treatment for prostate cancer, but preoperative determination of whether cancer has invaded the NVB can be difficult. The use of conventional body-coil magnetic resonance (MR) imaging to make this preoperative determination was evaluated in 50 patients with biopsy-proved cancer. All patients underwent radical retropubic prostatectomy after MR imaging. MR imaging, surgical, and pathologic data were correlated relative to tumor location and volume, Gleason grade, presence of capsular penetration, and depth of NVB invasion. The sensitivity of MR imaging for invasion was 68%, specificity was 59%, and overall accuracy was 64%. Results of this study indicate that MR imaging can help identify the NVB and predict invasion of the NVB by tumor, but the usefulness of the technique is limited by the lack of spatial resolution associated with use of the whole-body coil. PMID- 1887018 TI - Idiopathic intractable epistaxis: endovascular therapy. AB - Thirty patients with intractable idiopathic epistaxis were treated with endovascular therapy. Embolization of the internal maxillary artery controlled the epistaxis in 87% of the patients, and the success rate was increased to 97% after supplemental embolization of the facial artery. The only complication observed was transient postembolization hemiparesis, which occurred in one of the 30 patients. Intractable idiopathic epistaxis is defined as epistaxis of unknown cause that is refractory to nasal packing. Such epistaxis is commonly treated with surgical intervention, including ligation of the terminal segments of the internal maxillary artery and the ethmoid arteries. An alternative approach is performance of endovascular therapy. In our opinion, embolization is a safe and effective procedure when it is carried out by appropriately trained personnel. In most patients, its performance requires use of only neuroleptanalgesia; surgery can be avoided, and the duration of hospitalization is significantly shortened. We recommend that embolization be adopted as the primary modality for the treatment of idiopathic intractable epistaxis. PMID- 1887019 TI - Blunt splenic trauma and the angiographer: will we go back to the future? PMID- 1887020 TI - Comparison of CT, low-field-strength MR imaging, and high-field-strength MR imaging. Work in progress. AB - To assess objectively the sensitivity and specificity of low-field-strength (0.064 T) magnetic resonance (MR) imaging, a prospective blind study of 280 examinations was performed to compare low-field-strength MR imaging with computed tomography (CT) and with high-field-strength (1.5-T) MR imaging of the cranium. The sensitivity (defined as the true-positive rate) with high-field MR imaging was superior to that with low-field MR imaging and CT in helping detect overall abnormalities. Sensitivities were generally similar over a broad range of specific cranial central nervous system diseases. Low-field and high-field MR imaging were equivalent in the blind diagnoses of neoplasms and white matter disease, whereas low-field MR and CT were equivalent in the blind diagnoses of contusion, subdural and epidural hematoma, sinus disease, normality, and abnormality. The specificities with low-field MR imaging and CT were substantially better than those with high-field MR imaging. PMID- 1887021 TI - In utero analysis of fetal growth: a sonographic weight standard. AB - Regression analysis was used to develop an in utero fetal weight model from a population of 392 predominantly middle-class white patients with certain menstrual histories. There was a gradual increase in fetal weight from 35 g at 10 weeks to 3,619 g at 40 weeks, with uniform variance of +/- 12.7% (1 standard deviation) throughout gestation. When tested against the estimated weights of 1,771 chromosomally normal fetuses between 14 and 21 weeks, the mean percent difference was 0.8% and the average absolute percent error was 3.3%. When compared with actual delivery data for 163 fetuses in the group, the mean percent difference was 0.8% and the average absolute percent error was 1.1%. These data are compared with other prenatal weight curves obtained at ultrasound and with data from several large postnatal weight studies. PMID- 1887022 TI - Increased renal parenchymal echogenicity in the fetus: importance and clinical outcome. AB - Pre- and postnatal ultrasound (US) findings and clinical course in 19 fetuses (16 40 menstrual weeks) with hyperechoic kidneys (renal echogenicity greater than that of liver) and no other abnormalities detected with US were evaluated to determine whether increased renal parenchymal echogenicity in the fetus indicates renal disease. Four infants (21%) were healthy at birth and had normal postnatal sonograms. Another 10 infants (53%) survived, but abnormalities were found at neonatal US. Postnatal diagnoses in these 10 neonates included unilateral renal dysplasia (n = 3), unilateral multicystic dysplastic kidney and a contralateral hyperechoic kidney (n = 2), hydronephrosis (n = 2), and renal abnormalities of unknown type (n = 3). Five fetuses with either infantile polycystic kidney disease (n = 4) or bilateral multicystic dysplasia (n = 1) did not survive. Oligohydramnios was predictive of a poor prognosis. Hyperechoic renal parenchyma in the fetus was associated with sonographic or functional abnormalities in 15 of 19 cases (79%) and a 74% survival rate. PMID- 1887023 TI - Calcium oxalate microcalcifications in the breast. AB - Calcium oxalate calcifications can be difficult to detect with routine histologic procedures. In the reported case, microcalcifications that were evident with radiography of the specimen and of the paraffin blocks could not be detected with light microscopy. Polarized light microscopy, however, revealed the calcifications to be calcium oxalate crystals. Use of polarized light microscopy may resolve radiologic-pathologic discrepancies in such cases. PMID- 1887024 TI - Tumor invasion of the chest wall and mediastinum in lung cancer: evaluation with pneumothorax CT. AB - For preoperative evaluation of chest wall and mediastinal invasion by lung cancer, computed tomography (CT), combined with artificial pneumothorax (pneumothorax CT), was performed in 43 patients with lung cancer in whom conventional CT scans showed that the mass was contiguous to the chest wall (n = 30) and/or mediastinum (n = 25) but without evidence of definite tumor invasion. Invasion was diagnosed on the basis of whether an air space existed between the mass and the adjacent structures. In three patients pneumothorax was not produced. After the procedure, four patients developed symptomatic pneumothorax, and one, subcutaneous emphysema. Comparison of diagnoses based on findings at pneumothorax CT, surgery, and pathologic examination showed that pneumothorax CT is 100% accurate for chest wall invasion and 76% accurate for mediastinal invasion. The authors conclude that this procedure is helpful in accurate evaluation of the T criterion in lung cancer, especially for patients in whom findings at conventional CT suggest tumor invasion of the chest wall and mediastinum. PMID- 1887025 TI - Intrathoracic complications following allogeneic bone marrow transplantation: CT findings. AB - The authors retrospectively reviewed computed tomographic (CT) scans of 18 patients who developed 21 episodes of intrathoracic complications after allogeneic bone marrow transplantation (BMT). Pathologic and/or microbiologic diagnoses were available for all patients. All patients were immunocompromised due to either graft-versus-host disease (GVHD), neutropenia, or recurrent malignancy after BMT. CT demonstrated diagnostically relevant findings that were not apparent at radiography in 12 of the 21 cases (57%). These included a ground glass pattern in early pneumonia (n = 5); a peripheral distribution in GVHD, bronchiolitis obliterans organizing pneumonia, and eosinophilic drug reaction (n = 4); cavitating lesions in Pneumocystis carinii pneumonia (n = 1); hemorrhagic infarcts in aspergillosis (n = 1); and mediastinal adenopathy in recurrent Hodgkin disease (n = 1). The authors conclude that chest CT is superior to radiography in demonstrating the presence, distribution, and extent of intrathoracic complications developing in patients after allogeneic BMT. CT is useful in guiding procedures for tissue diagnosis. PMID- 1887026 TI - Assessment of diffuse infiltrative lung disease: comparison of conventional CT and high-resolution CT. AB - The diagnostic accuracies of conventional computed tomography (CT) and high resolution CT (HRCT) in examination of the entire lungs were compared prospectively, and the diagnostic utility of a limited number of HRCT sections in the evaluation of diffuse infiltrative lung disease (DILD) was determined in 150 consecutive patients. Conventional 10-mm CT sections were equivalent to 1.2-mm HRCT sections in the recognition of nodules, masses, nodular irregularities of the interfaces, large cystic air spaces, and architectural distortion. Conventional CT was superior to HRCT in the diagnosis of micronodules and infiltrates. However, 15% of micronodules were recognized only on HRCT images because of their small size and low density. Fine bronchial and parenchymal lesions were best seen on HRCT scans. HRCT was the only technique that allowed assessment of the presence of areas of ground-glass attenuation. HRCT improves visualization of small parenchymal structures and allows a confident evaluation of DILD, providing that the entire lungs are studied. Nevertheless, an optimal CT evaluation of micronodular patterns requires additional thick-section CT scans. PMID- 1887027 TI - Hyperechoic renal medullary pyramids in infants and children. AB - Fifty-five children (34 boys, 21 girls; age range, 1 day to 18 years) with increased echogenicity of the renal medullary pyramids at ultrasound evaluation were identified. The clinical diagnoses associated with hyperechoic medullary pyramids could be separated based on the presence or absence of hypercalciuria. Patients with drug-induced hypercalciuria included 10 infants treated with furosemide, two treated with long-term steroid therapy, and one treated with excessive amounts of vitamin D. Other clinical conditions associated with hypercalciuria included renal tubular acidosis (n = 10), Bartter syndrome (n = 5), hyperparathyroidism (n = 3), Williams syndrome (n = 2) and medullary sponge kidney (n = 2). Ten children with transient renal insufficiency and three with sickle cell disease had normal urine calcium concentration. Isolated disease entities accounted for the remainder of cases. A specific diagnosis can usually be made in a patient with hyperechoic renal medullary pyramids by using a systematic clinical approach that includes evaluation of patient age, serum and urine calcium concentration, and renal function. PMID- 1887028 TI - Air enema for diagnosis and reduction of intussusception: clinical experience and pressure correlates. AB - Air enema was used for exclusion, diagnosis, initial movement, and complete reduction of intussusception in 186 pediatric patients. Average pressure needed for initial movement of intussusception was 56.5 mm Hg; average maximum pressure of 97.8 mm Hg was required for complete reduction. Average fluoroscopy time required for intussusception reduction was 94.8 seconds; an average of 41.8 seconds was required to exclude intussusception. Intussusception was diagnosed in 75 patients, and reduction was accomplished in 65 (87%). Of 100 consecutive patients that underwent hydrostatic reduction of intussusception at the authors' institution, reduction was successful in 55. Compared with hydrostatic enema, air enema involves shorter fluoroscopy time and lower radiation dose to the patient. Air enema is safe and effective for diagnosis and treatment of intussusception in infants and children and has replaced hydrostatic enema for such procedures at the authors' institution. PMID- 1887029 TI - Dynamic hepatic CT: how many years will it take 'til we learn? PMID- 1887030 TI - Metabolic and destructive brain disorders in children: findings with localized proton MR spectroscopy. AB - The diagnostic potential of volume-selective proton magnetic resonance (MR) spectroscopy in vivo was evaluated in 20 children and young adults with various neurodegenerative brain disorders. All patients were examined with MR spectroscopy in conjunction with MR imaging of the brain on a whole-body imager at 1.5 T. Comparison of spectra in our patients with those of children with normal myelination (prominent signals from N-acetylaspartate [NAA], creatine/phosphocreatine, and choline) revealed a marked decrease of NAA in 12 of 17 patients with focal or generalized demyelination. In patients with Canavan disease, NAA signal intensity was markedly increased, but no choline signal was found. Increased signal intensity from lactate occurred in patients with Leigh disease, neuroaxonal dystrophy, Schilder disease, and Cockayne disease, which indicated a disturbed energy metabolism in the examined region. These results demonstrate that proton MR spectroscopy can be applied in a clinical environment to facilitate diagnosis of hereditary and acquired brain disorders in children. PMID- 1887031 TI - Right window for dynamic hepatic CT. PMID- 1887032 TI - Blunt splenic injuries: nonsurgical treatment with CT, arteriography, and transcatheter arterial embolization of the splenic artery. AB - The management and outcome of blunt splenic injury diagnosed with computed tomography (CT) were studied in 44 consecutive patients who were hemodynamically stable or whose condition stabilized rapidly with resuscitation. Celiac and splenic arteriography was used in the triage of patients for nonsurgical treatment or for hemostasis. Patients without arterial extravasation of contrast material at arteriography were treated with bed rest only (group 1, n = 19); patients who had such extravasation were treated with bed rest after percutaneous transcatheter coil occlusion of the proximal splenic artery (group 2, n = 17). Abdominal exploration without angiography or embolotherapy was begun if the patient or attending surgeon did not agree with the treatment protocol (group 3, n = 8). Treatment with bed rest alone was successful in 18 patients. Clinical control of hemorrhage was accomplished in all patients in group 2 and one patient in group 1. Thus, exploratory laparotomy was avoided in 34 of 36 patients (94%) in whom nonoperative management was attempted; splenic salvage was achieved in 35 of 36 patients (97%). PMID- 1887033 TI - Transrectal US in the diagnosis of localized colitis cystica profunda. AB - Colitis cystica profunda (CCP) mimicks rectal carcinoma, which makes distinguishing this benign lesion from the more common rectal neoplasm clinically and pathologically difficult. When transrectal ultrasound (US) was used in this case, three features of CCP were seen. There were multiple lesions, which did not penetrate beyond the submucosa. A large cystic component was seen, with a layer of uniform thickness in two of the three lesions. Non-solid contents and a lack of infiltration can be visualized at transrectal US, which helps diagnose CCP. PMID- 1887034 TI - Fluid collections developing after pancreatic transplantation: radiologic evaluation and intervention. AB - The usefulness of real-time sonography, duplex sonography, computed tomography (CT), cystography, diagnostic aspiration, and percutaneous drainage in the diagnosis and treatment of peri-pancreatic-transplant fluid collections was retrospectively assessed in 46 recipients of extraperitoneal pancreatic transplants. Forty-four abnormalities were identified in the extraperitoneal space at sonography, including four pancreatic pseudocysts associated with malfunction of the pancreatic duct, seven abscesses, six hematomas, nine urinomas, six early postoperative fluid collections that spontaneously resolved, six cases of pancreatitis, and six cases of vascular occlusion. Sonography (including pulsed Doppler sonography) was the procedure of choice in detecting fluid collections and diagnosing pancreatitis, rejection, vascular thrombosis, and pancreatic duct malfunction. CT was diagnostic in four of six hematomas; cystography was diagnostic in seven of nine urinomas. Sonographically guided percutaneous intervention enabled three patients to avoid surgery and allowed optimal surgical planning for six patients. PMID- 1887035 TI - Volvulus of the splenic flexure: radiographic features. AB - Six cases of splenic flexure volvulus were studied over a 14-year period. The patients were aged 15-62 years. Five of the six patients were mentally retarded, lifelong residents of a long-term-care institution. Two patients had congenital absence of normal colonic attachments; the other four patients had elongated mesocolons, presumably from chronic constipation. All patients underwent abdominal radiography, followed by a barium enema study. In the appropriate clinical setting, radiographic diagnosis of a splenic flexure volvulus is suggested when the following are seen: (a) a markedly dilated, air-filled colon wtih an abrupt termination at the anatomic splenic flexure; (b) two widely separated air-fluid levels, one in the transverse colon and the other in the cecum; (c) an empty descending and sigmoid colon; and (d) a characteristic beak at the anatomic splenic flexure at a barium enema examination. PMID- 1887036 TI - Chemical shift artifact: dependence on shape and orientation of the lipid-water interface. AB - On magnetic resonance images, chemical shift artifact (CSA) can be seen at a planar lipid-water interface oriented within the plane of the phase-encoding and section-select directions (ie, perpendicular to the frequency-encoding direction). Phantoms and a clinical case were used to demonstrate that when a lipid-water interface is curvilinear (eg, spherical) or planar but not oriented along the section-select direction, CSA may be absent or diminished. This effect can be seen at interfaces of normal structures (kidneys, bladder) as well as at interfaces with pathologic lesions such as lipid-containing dermoids. Not only is this effect dependent on section thickness, field of view, matrix size, and receiver bandwidth, but it is also strongly dependent on the orientation of the interface with respect to the section-select direction. Knowledge of the factors that can alter CSA is important since it is used to distinguish lipid-containing from nonlipid-containing structures of similar signal intensities. PMID- 1887037 TI - Clean and dirty shadowing at US: a reappraisal. AB - Clean and dirty shadowing are common phenomena in ultrasound (US) imaging. Clean shadowing is thought to be produced by sound-absorbing materials (ie, stones), and dirty shadowing is thought to be produced by sound-reflecting materials (ie, abdominal gas), but these properties are not consistent. To evaluate the characteristics of shadows behind different objects at US, the authors scanned two renal stones and a bovine femur (each of which had part of its surface artificially smoothed or roughened) and a tissue-mimicking phantom comprising air containing cylinders of different radii of curvature. The rougher and/or smaller the radius of curvature of the surface insonified by the sound beam, the cleaner was the shadow, independent of the composition of the underlying reflecting medium. Clean and dirty shadowing were primarily related to the properties of the surface of the shadowing object and provided little information about the structural nature of the object. PMID- 1887038 TI - Sonoelasticity imaging: results in in vitro tissue specimens. AB - The authors present a method for imaging tissue stiffness (sonoelasticity) that has been developed and tested in a laboratory setting by using in vitro canine and human prostate glands. A low-frequency acoustic source was used to induce vibration in tissue under examination, and a color Doppler ultrasound (US) instrument was modified to detect vibration amplitude. The resulting image is a color "map" of tissue vibration superimposed on conventional gray-scale US images. Stiffer tissues vibrated less in response to audible sound, regardless of echogenicity. Normal human and canine prostate glands demonstrated a uniform vibration pattern. Four of four human prostatic adenocarcinomas and two stiff inclusions injected into canine prostate glands demonstrated a lack of vibration in comparison with normal surrounding tissue. The authors conclude that while further study is necessary, sonoelasticity imaging may enhance the detection of neoplasms by enabling their identification solely on the basis of stiffness. PMID- 1887039 TI - Tumor vascularization: assessment with duplex sonography. AB - In this prospective study, the authors examined 123 patients with benign or malignant neoplasms (breast cancer, n = 44; liver neoplasms, n = 43; and tumors affecting other organs, n = 36) to establish general criteria for evaluation of neoplastic lesions by means of duplex sonography. The frequency shifts determined by means of different Doppler frequencies (2.31 or 3.75 MHz) were converted into flow velocities. Only the highest systolic peak flow velocity obtained from a lesion was used for statistical evaluation. Receiver operating characteristic curves showed that a flow velocity of 0.4 m/sec is the optimal threshold value with which to differentiate benign from malignant tumors. The data obtained in all lesions indicated that only positive findings are potentially reliable. It is concluded that negative results of sonography should not be used to diagnose the presence of a benign lesion. The resistive index of the tumors was of negligible importance. PMID- 1887040 TI - Polyclonal human immunoglobulin G labeled with polymeric iron oxide: antibody MR imaging. AB - Human polyclonal immunoglobulin (Ig) G was attached to a monocrystalline iron oxide nanocompound (MION), a small superparamagnetic probe developed for receptor and antibody magnetic resonance (MR) imaging. The resulting complex, MION-IgG, had a slightly negative surface charge, a molecular weight of 150-180 kDa, and 0.36 microgram of IgG attached per milligram of iron. After intravenous administration of MION-IgG to normal rats, most of the compound localized in liver, spleen, and bone marrow. In an animal model of myositis, MION-IgG caused reduced signal intensity (most apparent on T2-weighted spin-echo and gradient echo images) at the site of inflammation. No change in signal intensity existed after an injection of unlabeled MION. Site-specific localization of MION-IgG was corroborated with scintigraphic imaging with indium-111 IgG and MION-In-111-IgG and was confirmed histologically with iron staining. These results indicate that antibody MR imaging is feasible in vivo. Target-specific and antibody MR imaging could be easily extended to other applications, including detection of cancer, infarction, and degenerative diseases. PMID- 1887041 TI - T1-weighted snapshot gradient-echo MR imaging of the abdomen. AB - Magnetization-prepared ultrashort-repetition-time (snapshot) gradient-echo imaging is a technique of magnetic resonance (MR) imaging with many potential applications. In the application of this technique to abdominal imaging, the effects on contrast of phase-encoding order, resolution, preparation-phase inversion time, and data-acquisition flip angle were predicted and then demonstrated with images obtained in examinations of 22 patients. In the analysis of 36 liver lesions, snapshot images were compared with corresponding T1-weighted spin-echo images on the basis of signal-to-noise ratio (S/N) of liver and contrast-to-noise ratio (C/N) between liver and lesion. Snapshot MR imaging produced abdominal images with 192 (or 256) x 256 resolution, negligible motion artifact, and C/N 1.29 times (+/- 0.48) higher than that in T1-weighted spin-echo imaging. Acquisition times were 13 seconds or less, short enough for imaging during suspended respiration. Also, use of a phased-array multicoil further improves the S/N in snapshot images without acquisition-time penalty. PMID- 1887042 TI - Acute and chronic tears of the anterior cruciate ligament: differential features at MR imaging. AB - To evaluate the differential features of acute and chronic tears of the anterior cruciate ligament at magnetic resonance (MR) imaging, the authors performed a retrospective evaluation of findings in 81 MR examinations correlated with results at arthroscopy. Intact anterior cruciate ligaments (ACLs) were present in 29 patients; acute complete ACL tears, in 22; and chronic complete ACL tears, in 30. Acute tears were accurately distinguished from intact ligaments and were characterized by the presence of edema. Chronic tears had a more variable appearance: Nine (30%) were depicted at MR as intact bands with low signal intensity that bridged the expected origin and insertion of the ACL. This appearance is likely due to the presence of bridging fibrous scars within the intercondylar notch. Five of these nine cases were correctly characterized as chronically torn because of the presence of focal angulation. In four of these nine cases the scarred fragments produced a relatively straight band that mimicked an intact ligament. Although chronic and acute ACL tears usually have distinct findings at MR, a chronic tear will occasionally be difficult to distinguish from an intact ligament. PMID- 1887043 TI - Progression of meniscal degenerative changes in college football players: evaluation with MR imaging. AB - Intrameniscal degenerative changes, presumably due to mild repetitive trauma, have been shown in many college and professional athletes, but it is uncertain over what period of time they can develop or significantly progress. To ascertain this period, the authors used magnetic resonance (MR) imaging to examine one knee in each of 20 players in the starting lineup of a major college football team before and after the season. Only asymptomatic knees (right, n = 10; left, n = 10) were examined; the images were reviewed blindly by one experienced observer without reference to the other examination. A significant progression existed in the grade of signal intensity shown in the menisci over the course of the season (P less than .001). Although this is a small study covering only 1 year, these preliminary results suggest that significant degeneration can occur in the menisci of asymptomatic players over a single season. PMID- 1887044 TI - Exercise-induced muscle modifications: study of healthy subjects and patients with metabolic myopathies with MR imaging and P-31 spectroscopy. AB - Exercise-induced variations in proton signal intensity at magnetic resonance (MR) imaging and in intracellular pH were studied in the forearm muscles of healthy subjects and patients with muscular glycogenoses. The relative increase in T2 was measured from MR images obtained at 0.5 T, and end-exercise pH was measured with surface coil phosphorus-31 spectroscopy at 2 T. Eight healthy subjects showed a relative increase in T2 ranging from 20% to 44% in the flexor digitorum superficialis muscle and a drop in pH ranging from 0.35 to 1.1. Seven patients with muscular glycogenosis (six with McArdle disease and one with phosphofructokinase deficiency) showed only a slight variation in T2 (0%-17%) and no decrease in pH. Variations in T2 and in end-exercise pH were found to be correlated, perhaps reflecting the stimulation of muscular perfusion caused by acidosis. PMID- 1887045 TI - Effect of arm rotation on MR imaging of the rotator cuff. AB - The effect of humeral rotation on the appearance of the rotator cuff tendon in oblique coronal magnetic resonance images was evaluated in 70 such images. Internal rotation produced overlap of the supraspinatus and infraspinatus tendons with soft-tissue interposition or apparent discontinuity of the tendon in 22 cases, including 14 of 15 shoulders positioned in the first 30 degrees between extreme internal and external rotation. Imaging in internal rotation makes assessment of the tendon difficult and should be avoided. PMID- 1887046 TI - Osteoid osteoma: CT-guided percutaneous treatment. AB - Seven patients with presumed osteoid osteoma were treated with percutaneous destruction or drill resection with computed tomographic (CT) guidance. The diagnosis of osteoid osteoma was made on the basis of findings in the clinical history and results at plain radiography, bone scintigraphy, and CT. In four patients, histologic confirmation was obtained. Hospital stay lasted from 1 to 3 days. After 11-38 months of follow-up examinations, all patients were asymptomatic. The authors report this simple procedure as an alternative to the more traditional open surgery technique. PMID- 1887047 TI - Standards for evaluating and reporting the results of surgical and percutaneous therapy for peripheral arterial disease. AB - By adopting precise definitions of essential terms, developing objective criteria by which the various measures of success or failure can be judged, and establishing a standardized scheme by which severity of disease, degrees of improvement or deterioration, and risk factors that affect outcome can be graded, the quality of published reports of revascularization procedures for lower extremity ischemia can be greatly improved, allowing comparative evaluation of treatment modalities. PMID- 1887048 TI - Small, deep pelvic abscesses: definition and drainage guided with an endovaginal probe. AB - Four small, deep pelvic abscesses were easily drained transvaginally by using an endovaginal transducer for guidance, support, and continuous monitoring of catheter placement. Collections that could not be drained percutaneously or at surgery were effectively managed with this technique. An inexpensive guide (estimated cost, $1.65) facilitated control of the catheter. All four abscesses resolved without further intervention. PMID- 1887049 TI - Needle holder for use with a biopsy gun. AB - The authors designed and constructed a simple needle holder device for maintaining the position of the trocar and cannula before performance of computed tomography (CT)- and ultrasonography-guided biopsies with a biopsy gun. The holder can be removed before attachment of the biopsy gun and routine obtaining of tissue. Use of the holder facilitated quicker and easier CT-guided biopsies of the liver (n = 3), pancreas (n = 1), and adrenal gland (n = 1) and of a chest wall tumor. PMID- 1887050 TI - Double-lumen central venous catheter for percutaneous ureteral perfusion studies. AB - A commercially available double-lumen central venous catheter that can be inserted over a 0.018-inch guide wire was used for ureteral perfusion studies in three infants. Complications or difficulties were not encountered in any patients. This technique allows simultaneous monitoring of perfusion and intrarenal pressure and requires only a single puncture of the renal pelvis with a 21-gauge needle. PMID- 1887051 TI - Mammography in women 35 years of age and younger. PMID- 1887052 TI - Inconsistencies in mammographic phantoms used for ACR accreditation. PMID- 1887053 TI - Real-time interactive color flow MR imaging. AB - Real-time interactive color flow magnetic resonance (MR) imaging is a combination of real-time MR imaging and color encoding of velocity-induced phase angle. Flow compensated (FC) and flow-encoded (FE) images are acquired continuously by using gradient echoes and a 12-msec repetition time. Each image is reconstructed within 200 msec of acquisition, and the FC magnitude image is displayed in gray-scale format. The phase difference between the reconstructed FC and FE images, a difference proportional to velocity along the flow-encoding direction, is encoded in color and superimposed on the gray-scale FC image. Magnitude and phase information are thus presented simultaneously. The viewer may interactively adjust many acquisition parameters during data acquisition. Experimental results of phantom and in vivo human studies validate the method. Characteristics of the color flow MR imaging technique are compared with those of duplex color ultrasound. PMID- 1887054 TI - Combined chemical-shift and phase-selective imaging for fat suppression: theory and initial clinical experience. AB - Incomplete fat suppression with a chemical-shift-selective (CHESS) or phase selective (Dixon) technique is partially due to the olefinic fat component, which precesses at the same frequency as water. The authors developed a new method of fat suppression--the opposed-fat saturation (OP-ES) sequence--that combines both techniques to obtain superior fat saturation. Fat suppression was verified in phantom studies, which showed that the CHESS portion can eliminate most of the aliphatic fat signal except for a small residual component because of steady state effects and magnetic field imperfections. This residual component is cancelled by the olefinic fat with the phase-selective opposed portion of the sequence. Furthermore, this sequence was superior to another hybrid technique, chopper Dixon in combination with CHESS. When used in 10 healthy volunteers, the OP-FS sequence showed consistently better suppression of the subcutaneous and retroperitoneal fat compared with CHESS alone. Additional advantages for clinical abdominal imaging include its compatibility with respiratory compensation, use of a single excitation, and ease of implementation with gradient-echo imaging. Preliminary application in 10 patients illustrated other potential advantages, including clarification of fat-containing diseases and increasing conspicuity of some lesions. PMID- 1887055 TI - Pelvic abscesses: CT-guided transrectal drainage. AB - Percutaneous drainage of pelvic abscesses has been performed by using a number of approaches, including transabdominal, transgluteal, and transrectal. The authors present a technique for the drainage of pelvic abscesses by a transrectal route with use of computed tomographic (CT) guidance. Equipment for the technique included a plastic introducer tube, standard needle, angiographic guide wire, and pigtail catheters. The pelvic abscesses of 10 patients (six after appendectomy, three after colon resection, one secondary to diverticulitis) were successfully drained by using the new technique. No complications or recurrences were experienced. After initial catheter placement, patients were treated with use of gravity drainage and appropriate antibiotics. Success of drainage was determined with sequential CT scans. Compared with the transgluteal approach, the transrectal approach offered increased patient comfort and minimal risk of potential complications such as injury to the sciatic nerve or tracking of the abscess. Use of the plastic introducer tube promoted operator safety by protecting the guiding finger. On the basis of this initial series, CT-guided transrectal drainage appears to be an effective and well-tolerated method for the drainage of pelvic abscesses. PMID- 1887056 TI - US-guided transvaginal drainage of pelvic abscesses and fluid collections. AB - Ultrasound (US)-guided transvaginal needle or catheter drainage was performed in 14 women for a variety of pelvic abscesses and fluid collections; tubo-ovarian abscesses and postoperative collections were most common. Diagnosis was achieved in all 14 patients (100%), including one patient with suspected ovarian carcinoma who underwent only diagnostic needle aspiration and no therapeutic drainage. Abscesses or fluid collections were evacuated in 13 of 13 patients (100%) with either needle (n = 7) or catheter (n = 6) drainage (with appropriate antibiotics). Twelve of the 14 patients (86%) were spared an operation; surgery was undertaken in two patients for a persistent tubo-ovarian phlegmon. No major complications were associated with drainage. Catheters were removed an average of 6.7 days after insertion. The success, safety, and advantages of US-guided transvaginal drainage in our early experience suggest its use as an alternative to standard percutaneous catheter procedures to diagnose and drain certain pelvic abscesses and fluid collections. PMID- 1887057 TI - Myocardial high-energy phosphate metabolism and allograft rejection in patients with heart transplants. AB - To determine whether myocardial high-energy phosphate metabolism is altered in cardiac allograft patients undergoing rejection, 14 patients with heart transplants were examined with image-guided, one-dimensional, phase-encoded surface-coil phosphorus-31 nuclear magnetic resonance (NMR) spectroscopy on 19 occasions 39-2,021 days after transplantation. On average, patients underwent mild rejection (detected with endomyocardial biopsy) and had a reduced ratio of anterior myocardial phosphocreatine (PCr) to adenosine triphosphate (ATP) (1.57 +/- 0.50 [standard deviation] vs 1.93 +/- 0.2; P less than .01) compared with that of 17 healthy control subjects. Ratios of PCr to inorganic phosphate also appeared lower whenever detectable. However, P-31 NMR spectroscopy did not permit reliable identification of patients who required augmented therapy for rejection detected with biopsy either on the day of the P-31 NMR spectroscopic study or at the next scheduled biopsy 10-140 days thereafter (sensitivity, 50%, and specificity, 73% with use of cardiac-averaged PCr/ATP values for each heart; sensitivity, 88%, and specificity, 55% with use of the lowest myocardial PCr/ATP ratios measured in each heart). PMID- 1887058 TI - Occlusive and reperfused myocardial infarcts: MR imaging differentiation with nonionic Gd-DTPA-BMA. AB - To increase the time during which effective contrast exists between normal and infarcted myocardium, a high dose (0.6 mmol/kg) of the nonionic contrast medium gadolinium diethylenetriaminepentaacetic acid bismethylamide (Gd-DTPA-BMA) was used to distinguish between occlusive and reperfused myocardial infarctions in rats. After administration of Gd-DTPA-BMA, there was clear and persistent demarcation of both occlusive and reperfused infarcts on T1-weighted MR images. In occlusive infarcts, normal, infarcted, and periinfarcted myocardium could be identified. High signal intensity was evident for 60 minutes in a band straddling the border between infarcted and normal myocardium, namely, the periinfarction zone. In the reperfused infarct, normal and infarcted myocardium could be identified. The reperfused zone was immediately enhanced after injection of Gd DTPA-BMA. A differential pattern of enhancement between occlusive and reperfused myocardial infarcts was evident for 1 hour. Thus, Gd-DTPA-BMA has the potential to allow (a) depiction of occlusive and reperfused acute myocardial infarcts, (b) documentation of reperfusion of myocardial infarction, and (c) distinction between occlusive and reperfused infarction. PMID- 1887059 TI - Penetrating atherosclerotic aortic ulcer with dissecting hematoma: control of bleeding with percutaneous embolization. AB - A case is presented in which left subpleural hematoma and hemothorax resulted from a penetrating atherosclerotic aortic ulcer with an aortic pseudoaneurysm and intramedial hematoma. Percutaneous transfemoral embolization of the ulcer with use of coils and thrombin resulted in stabilization of the patient's hemodynamic status. The patient died 6 days later of pneumonia. In certain clinical situations, treatment of bleeding from penetrating aortic ulcers with percutaneous embolization may stabilize the patient's condition, allowing elective surgical intervention. PMID- 1887060 TI - Hemodialysis grafts: color Doppler flow imaging correlated with digital subtraction angiography and functional status. AB - Twenty-two patients with hemodialysis grafts were prospectively evaluated with color Doppler flow imaging and digital subtraction angiography (DSA). Eighteen patients had normal functional parameters during hemodialysis, and four had increased venous pressure during hemodialysis. Color Doppler flow imaging allowed identification of nine macroaneurysms related to wall degeneration, two cases of spontaneous fistula formation between the graft and peripheral veins, and 20 stenoses. Use of color Doppler flow imaging led to overestimation of the degree of stenosis at the venous anastomosis when compared with use of angiography. Three cases of subclavian venous stenosis were identified only at angiography. Color Doppler flow imaging appears accurate in the detection of stenoses and seems sufficient for follow-up of normally functioning grafts. However, because of its low sensitivity for identification of proximal stenoses and the necessity of obtaining an angiogram to plan surgical or percutaneous correction, DSA remains the technique of choice. PMID- 1887061 TI - Hyperechoic renal medullary pyramids in infants and children. PMID- 1887062 TI - Carcinoma of the uterus: use of gadopentetate dimeglumine in MR imaging. AB - This prospective study assessed the role of gadopentetate dimeglumine-enhanced magnetic resonance imaging in the detection and staging of carcinomas of the endometrium and cervix. Surgical-pathologic findings were used as the standard of reference. In the evaluation of endometrial carcinoma, contrast-enhanced imaging improved tumor detection and differentiation between viable tumor and retained debris. Use of contrast material significantly improved the staging accuracy. The ability to assess the depth of myometrial invasion was also improved. In the evaluation of cervical carcinoma, assessment of tumor location and size did not improve following contrast enhancement. Use of gadopentetate dimeglumine resulted in overestimation of stromal, parametrial, vaginal, and/or bladder wall invasion in eight patients. However, evaluation of intratumoral architecture and large lesions was easier with contrast-enhanced imaging. When only stage II and higher disease was analyzed, use of contrast material improved the evaluation of disease extent. The authors conclude that gadolinium enhancement adds to the accuracy of evaluation of endometrial carcinoma but is useful in only advanced cases of cervical carcinoma. PMID- 1887063 TI - The potential role of vitamin E in the treatment of immunologic abnormalities during acquired immune deficiency syndrome. AB - The literature is briefly summarized as to immunologic modifications caused by the human acquired immune deficiency syndrome (AIDS), immunocompetence at various nutritional states of vitamin E, and the immunoenhancing properties of vitamin E. The abnormalities of immune components present in AIDS are similar to those that are stimulated or restored by intake of high doses of vitamin E. Dietary supplementation of vitamin E with an adequate nutrition support or concomitant use of this vitamin with current drug therapies [For example, Zidovudine (AZT)] may increase the therapeutic efficiency of drugs and enhance immune resistance to opportunistic infections associated with AIDS. Supplementation with vitamin E may also decrease the progression of the disease to AIDS. Unlike many pharmacological agents which are toxic at low levels, vitamin E is non-toxic over a wide range of intakes. A moderately high dose may be used to target and stimulate some specific immune cells destroyed by HIV infection. However, further interdisciplinary studies are much needed to relate various levels of intake of this vitamin as a supplement to clinical outcomes during HIV infection and establish the role for this vitamin in human immunity during AIDS. PMID- 1887064 TI - Dietary fat quality and circulating cholesterol levels in humans: a review of actions and mechanisms. AB - Consumption of saturated fats contributes to elevated circulating cholesterol levels, whilst either polyunsaturated or monounsaturated fats are linked to depressed levels. Since elevated serum cholesterol is a risk factor for coronary heart disease, it is of interest to understand the factors responsible for the responses elicited by dietary fat quality. Changes in faecal sterol excretion, exogenous cholesterol absorption, lipoprotein composition, and lipoprotein catabolism can coincide with changes in fat intake but may not necessary cause them. Whether or not rates of whole-body cholesterol synthesis respond to dietary fat quality is not known. To date, animal studies suggest that shifts in LDL receptor-mediated cholesterol transport are to blame for responses of circulating cholesterol levels to dietary fat. PMID- 1887065 TI - Folate status and the immune system. AB - Folic acid plays a crucial role in DNA and protein synthesis, suggesting that every mechanism in which cell proliferation intervenes may be altered. Cell mediated immunity is especially affected by folate deficiency: the blastogenic response of T lymphocytes to certain mitogens is decreased in folate-deficient humans and animals, and the thymus is preferentially altered. The effects of folic acid deficiency upon humoral immunity have been more thoroughly investigated in animals than in humans, and the antibody responses to several antigens have been shown to decrease. Conversely, the phagocytic and bactericidal capacities of polymorphonuclear cells have been studied mainly in folate deficient humans. However results in this field are controversial. Alterations in immune system functions could lead to decreased resistance to infections, as commonly observed in folate-deficient humans and animals. PMID- 1887066 TI - Diet-disease relationships: public health perspectives. AB - Recent nutrition recommendations are directed towards prevention of chronic degenerative diseases, particularly coronary heart disease and cancer. This focus is in response to morbidity and mortality trends during this century. The evidence supporting such dietary changes remains inconclusive because of difficulties inherent in the measurement of usual dietary intake. The association between dietary fat and breast cancer is reviewed as an example of the problems faced in assessing whether a dietary component does alter the risk of disease. Current recommendations suggest a population-based approach to dietary modifications; the public health implications of this approach are discussed. PMID- 1887067 TI - Insulin receptors in the central nervous system: localization, signalling mechanisms and functional aspects. PMID- 1887068 TI - The pedunculopontine nucleus. AB - In an effort to account for a large number of reported functions mediated by a small portion of the midbrain, a hypothesis is advanced as a basis for discussion and not as established fact and is guided by reports from a large number of laboratories working on the same region but using widely disparate preparations. Overall, the hypothesized model suggests an underlying mechanism of action for what is essentially the ascending reticular activating system. The model proposed will hopefully be tested stringently in order to arrive at a better understanding of brain stem mechanisms modulating a host of rhythmic functions. PMID- 1887069 TI - Case #2. Traumatic ulcer. PMID- 1887070 TI - Reading, writing and brushing. PMID- 1887071 TI - Pain of long hours standing and sitting. PMID- 1887072 TI - Difficult, but vital treatment. PMID- 1887073 TI - Avoid infection control overkill. PMID- 1887074 TI - Case #3. Nicotine stomatitis. PMID- 1887075 TI - More or less? PMID- 1887076 TI - Delivering care to the homeless. PMID- 1887077 TI - Door openers. Adding to your education can be a plus. PMID- 1887078 TI - Crimes against young patients. PMID- 1887079 TI - Return of the missing teeth. PMID- 1887080 TI - Your patient and Prozac. PMID- 1887081 TI - Routine gloving common practice. PMID- 1887082 TI - Case #5. Benign migratory glossitis. PMID- 1887083 TI - Clothing choice still confusing. Questions still remain concerning selection of protective wear. Guidelines do help in the decision-making process. PMID- 1887084 TI - Case #6. Squamous papilloma. PMID- 1887085 TI - The older patient. PMID- 1887086 TI - The flu that won't leave. PMID- 1887087 TI - Your patient and penicillin. PMID- 1887088 TI - Case #7. Mucous retention cyst. PMID- 1887089 TI - A valuable diagnostic tool for patient care. PMID- 1887090 TI - The many faces of our profession. PMID- 1887091 TI - Your patient and antibiotics. PMID- 1887092 TI - Combating risk of transmission. PMID- 1887093 TI - Florida AIDS cases raise ethical concerns. PMID- 1887094 TI - Case #8. Major aphthous ulcer. PMID- 1887095 TI - One on the way. PMID- 1887096 TI - Guarding against HIV. PMID- 1887097 TI - Seeking normalcy: the experience of coronary artery bypass surgery. AB - The aim of this study was to describe the experience of coronary artery bypass surgery (CAB) from the patient's perspective. A grounded theory method was used to explore the postoperative experiences of eight men and one woman following CAB surgery. The major process individuals engaged in following CAB surgery was seeking normalcy which involved three conceptual stages: surviving, restoring, and being fixed. Some individuals sought other explanations for the symptoms accompanying heart disease. An understanding of patient experiences regarding the nature of cardiovascular disease through the experience of surgery regimens may contribute to the assessment and intervention strategies used by health care providers in the postoperative care of these patients. PMID- 1887098 TI - Discovering older women's experience of urinary incontinence. AB - Grounded theory was used to acquire an understanding of older women's experience of urinary incontinence (UI). Women explained that accidents or other problems related to the UI were threats to their self-esteem. These threats provided strong incentives to develop an effective continence care system which would help to protect their self-esteem. If they were successful in developing an effective system, it was possible that they could accept the UI and lead "normal" lives. Examination of the data using the constant comparative method revealed the self care system that the women in this study produced to manage the UI, but not how they developed or sustained it. Further investigation into how women with UI develop and sustain continence care routines is needed, so that nurses can provide better assessments and nursing care. PMID- 1887099 TI - Releasing restraints: providing safe care for the elderly. AB - To examine the behavioral effects of releasing restraints and the feasibility of caring for patients considered at risk if unrestrained, two patients were continuously videotaped using surveillance cameras for 1 week with and 1 week without restraints. The videotapes were coded and analyzed using nonparametric and parametric statistics. In Patient #1, motor behavioral changes with a decrease of restless behaviors, as well as changes in sleeping position, were observed. There were no changes in verbal behavior. For Patient #2, no changes in motor or verbal behavior were observed. Nursing care showed a non-significant decrease in nursing care time and an increase in the number of nursing contacts. The implications of the findings and the use of videotapes as a method for collecting observational data in the clinical area are discussed. PMID- 1887100 TI - A model of parenting stress. AB - A preliminary theoretical model of parenting stress was tested. The additive effects of a series of stresses, namely, stressful pregnancy, stress of labor and delivery, and the stress of parenting were examined in a causal model of parenting stress. Factors theoretically expected to be protective in stressful circumstances, like, personality strength, prior experience, age, education, and social support, were predicted to be negatively related to stress. Data from 101 mothers whose infants were 6 weeks old were analyzed using path analysis. The data fit the model and explained 41% of the variance in parenting stress. The empirical model showed significant paths from prior experience and social support to the stress of pregnancy. The mother's education was the only significant variable in the pathway to labor and delivery stress and it was positively related to stress. Paths to parenting stress existed from personality and from pregnancy stress, but not from labor and delivery stress or any of the other variables. PMID- 1887101 TI - Remarriage and health. AB - One hundred and five adult females and 100 adult males from the mid-Missouri area participated in a study to compare the health complaints of remarried women and men and to determine correlates of these health complaints. A structured interview format was used to gather information, and each subject completed the Dyadic Adjustment Scale (DAS) and the Inventory of Family Feelings (IFF). No major health differences between women and men were found, although women experienced more changes in health complaints following remarriage than men did. Overall, the health of both men and women was affected most by their feelings toward one another and by having decision-making power within the family. For men, more decision-making power in the family and high marital satisfaction were associated with better health. For women, health was associated with positive feelings toward their spouse and less decision-making power. In addition, a woman's health was better with fewer children in the family and when all the children in the household were hers. PMID- 1887102 TI - Nurse burnout: work related and demographic factors as culprits. AB - This study was an examination of the combined ability of perceived work environment, demographic, and work-related variables to predict burnout among 314 nurses at a large metropolitan hospital. The three dimensions of burnout measured were emotional exhaustion, depersonalization, and personal accomplishment. High work pressure and low work involvement and supervisor support predicted emotional exhaustion. Task orientation, work pressure, work involvement, and age predicted both depersonalization and personal accomplishment. Burnout among nurses on each of the three work shifts also was examined. Results are discussed from the perspective of how to decrease or to prevent burnout among nurses. PMID- 1887103 TI - Utilizing research assistants and maintaining research integrity. AB - The appropriate use and supervision of research assistants is essential to the success of a research study and the avoidance of academic misconduct. The focus of this article is to provide guidelines for the new principal investigator regarding hiring, contracting, orienting, monitoring, and evaluating research assistants. Particular attention is given to techniques that will avoid academic misconduct resulting from research assistants being uninformed or unsupervised. PMID- 1887104 TI - Focus on psychometrics. Estimating construct validity. AB - The meaning of construct validity and techniques for its estimation are discussed. Of particular interest is the appropriate role of factor analysis (and related techniques) in construct validation efforts. A comprehensive view of construct validity is encouraged, as well as a cautious interpretation of the construct validity evidence available for many existing instruments. PMID- 1887105 TI - Re: "Focus on psychometrics: internal consistency estimates of reliability". PMID- 1887106 TI - [College of the History of Medicine of Buenos Aires. Presence of dentists and dental issues in its 2 periods]. PMID- 1887107 TI - [Notes for the history of dentistry (continued). The XVII century. Medicine and science]. PMID- 1887108 TI - [50 years of Argentine dentistry. (1900-1950)]. PMID- 1887109 TI - The 1990 Pilot Videodisc Project. PMID- 1887110 TI - Imaging of pediatric ovarian masses. AB - Ultrasonography is generally the initial diagnostic study of choice for evaluating suspected or known genital masses in young girls and adolescents. The authors reviewed the sonographic anatomy of the normal ovary and the sonographic spectrum in 88 pediatric patients with a variety of ovarian masses: simple and hemorrhagic cyst, teratoma, malignant tumor, tuboovarian abscess, torsion, and ectopic pregnancy. Among the various sonographic patterns observed, those of cystic ovarian masses and complex masses with mural nodules were the most specific, representing simple cysts and benign teratomas, respectively. Sonographic features of the remaining conditions were often similar, and diagnosis required correlation with clinical data and computed tomographic or magnetic resonance imaging findings. PMID- 1887111 TI - Left infrarenal region: anatomic variants, pathologic conditions, and diagnostic pitfalls. AB - Computed tomography (CT) is the preferred method for evaluating the left periaortic infrarenal region. Structures larger than 11 mm in cross-sectional diameter in this region are considered abnormal and should be evaluated for lymphadenopathy, hydroureter, or a vascular abnormality such as venous thrombosis or varicoceles. Normal structures include inferior mesenteric vessels, left gonadal vein and artery, and ureter. The diagnostic process may be complicated by variations in anatomy, including double inferior vena cava, left inferior vena cava, retroaortic left renal vein, circumaortic left renal vein, horseshoe kidney, crossed-fused renal ectopia, renal agenesis, and ureteral duplication. Familiarity with the anatomy of this region and awareness of normal variants are necessary to avoid errors in diagnosis. Radiologists should also be aware of problems in CT technique (nonopacified bowel, dynamic and unenhanced scanning) that can confuse the diagnosis. PMID- 1887112 TI - Incidental detection of urinary tract abnormalities with skeletal scintigraphy. AB - Urinary tract abnormalities are detected as incidental findings in 15% of skeletal scintigraphic studies. Several scintigraphic patterns denote these abnormalities. Bilateral diffuse increased uptake is found in patients who have undergone chemotherapy and those with hyperparathyroidism, hypercalcemia, and sickle cell disease. Bilateral diffuse decreased uptake occurs in patients with end-stage renal disease, extensive metastatic disease to the bone, and various hematologic disorders. Focal increased activity is associated with postoperative changes and effects from radiation therapy. Focal decreased uptake is caused by space-occupying lesions such as abscesses, cysts, and neoplasms. Abnormal size, shape, and position associated with abnormalities of the kidney and bladder can also be seen. Although these scintigraphic patterns are seldom suggestive of a definitive diagnosis, they are highly specific for urinary tract disease. PMID- 1887113 TI - Meaningful tort reform? Don't count on it. PMID- 1887114 TI - Complications of radiation therapy: CT evaluation. AB - Radiation therapy is an important technique for treating cancer. In the evaluation of the results of radiation therapy with computed tomography (CT), radiation-induced injuries to normal tissues are often detected. Common complications include pneumonitis, calcified lymph nodes, gastric ulceration, enteritis, hepatitis, cystitis, nephritis, osteitis, and insufficiency fractures. Rare complications include spontaneous pneumothorax, thymic cysts, vascular calcifications, and osseous sarcomas. Radiation-induced injury can usually be diagnosed from characteristic CT appearances and knowledge of the radiation port, radiation dose, and time interval since therapy. CT findings that cannot be explained on the basis of radiation therapy or that are suggestive of recurrent disease must be further evaluated. PMID- 1887115 TI - Bone marrow transplantation: clinical and radiologic aspects. AB - With the advent of histocompatibility typing, use of bone marrow transplantation for treating hematogenous cancer has dramatically increased. Marrow grafting is preceded by intense immunosuppressive, marrow ablative treatment, usually with high-dose chemotherapy and whole-body irradiation. Because the recipient may be immunocompromised for months after transplantation due to this regimen, complications are numerous. Complications are classified according to the following intervals: pre-engraftment (from pretransplantation treatment to engraftment), postengraftment (3 months afterward), and delayed (longer than 3 months after engraftment). Pre-engraftment complications include bacterial, fungal, and viral infections; tissue-damaging effects (eg, toxic pneumonitis); hepatic veno-occlusive disease; and graft rejection. Postengraftment complications include viral, fungal, and protozoal infections; acute graft-versus host disease (GVHD); and pneumatosis intestinalis. Delayed complications include chronic GVHD and recurrence of cancer. As part of the follow-up team, radiologists should be familiar with clinical aspects of marrow transplantation and be alert for early, potential life-threatening complications. PMID- 1887117 TI - Agricultural disorders of the lung. AB - Agricultural workers are at risk for developing many respiratory tract disorders. Crop production disorders include chronic bronchitis, asthma, organic dust toxicity syndrome, chemical poisoning, farmer lung, and silo-filler disease. Livestock production disorders include toxic manure poisoning (dung lung) and several zoonoses. Radiographic manifestations can be classified into three patterns: (a) normal findings, characteristic of chronic bronchitis, asthma, or organic dust toxicity syndrome; (b) acute diffuse interstitial or alveolar pattern, characteristic of farmer lung, silo-filler disease, dung lung, and chemical poisoning; and (c) chronic interstitial pattern in the upper lobes (farmer lung) or lower lobes (silo-filler disease, paraquat poisoning). Differential diagnosis is aided by knowledge that most of these disorders have a seasonal presentation. Zoonoses generally exhibit focal areas of consolidation in the lung: The type of splenic calcification, presence of mediastinal or hilar adenopathy, and development of bronchiectasis are additional findings useful in differentiating these rare infections. PMID- 1887116 TI - MR imaging of periosteal and cortical changes of bone. AB - The changes seen in the periosteum and cortical bone are fundamental radiographic features of bone disease. The basic radiographic findings used for diagnosis of bone lesions (patterns of cortical destruction and of periosteal new bone formation) can be well identified with magnetic resonance (MR) imaging. The authors used comparative radiographic, computed tomographic, and MR images to illustrate patterns of periosteal reaction (simple, laminated, spiculated, Codman triangle), geographic and permeative cortical destruction, cortical erosion, cortical expansion and continuity, and intraosseous and extraosseous calcification. The only feature not well demonstrated by MR imaging is pattern or extent of soft-tissue calcification. Although MR images are not required for diagnosis of most peripheral bone lesions, when they are obtained, these fundamental diagnostic features should not be ignored. PMID- 1887118 TI - Radiographic caricature as a medical illustration. PMID- 1887119 TI - Vascular rings: 10-year review of imaging. AB - Radiologic studies of 47 children with surgically proved vascular rings were retrospectively reviewed. On radiographs, a right-sided or bilateral aortic arch and the presence of tracheal narrowing were signs indicative of vascular rings. On barium esophagograms, a double or right aortic arch appeared as deep persistent posterior indentation of the esophagus. On computed tomographic (CT) scans and magnetic resonance (MR) images, the diagnosis of vascular rings was based on vascular branching patterns, the side of the aortic arch or presence of two arches, and narrowing of the airway. Although the diagnosis of a complete vascular ring can usually be established with certainty by means of radiography and esophagography, CT and MR imaging add valuable anatomic detail about exact arch configuration, tracheobronchial compression, and brachiocephalic vessel branching. PMID- 1887120 TI - CT of lymphoma: spectrum of disease. AB - Computed tomography (CT) is the study of choice for the detection and staging of Hodgkin and non-Hodgkin lymphoma. CT enables accurate measurement of both tumor extent and volume and provides information that can be used to plan an appropriate therapeutic regimen as well as follow patient response to therapy. This article presents a systematic review of the common and uncommon appearances of lymphoma in the chest and abdomen. Potential pitfalls and limitations of CT in staging and follow-up are also addressed. PMID- 1887122 TI - Development of radiation protection standards. AB - Radiation protection standards are based on the best available knowledge, caution, and perception. Dose limits for occupational exposure have decreased as knowledge was gained about radiation effects: from 0.6 Sv (60 rem)/year for 1900 1930 to 50 mSv (5 rem)/year in 1958 (the level still used as of 1990). Current dose limits for public exposure range from 1 mSv to 5 mSv, depending on frequency of exposure. For the embryo and fetus, dose limits are 0.5 mSv/mo and 5 mSv for the entire gestation. In the 1970s, the concept of acceptable risk and that of a non-threshold dose-response relationship became the basis for setting dose limits. Three principles of radiation protection are that (a) dose levels should not exceed acceptable levels, (b) optimal dose levels should be as low as reasonably achievable, and (c) radiation should not be used unless it produces a positive net benefit. Although no dose limits have been set for patients undergoing diagnostic and therapeutic radiologic procedures, such measures must provide a net benefit to patients at optimal dose levels. PMID- 1887121 TI - Osteoid osteoma. AB - Osteoid osteoma is a benign skeletal neoplasm composed of osteoid and woven bone that rarely exceeds 1.5 cm in greatest dimension. The lesion is most commonly located in the cortex of long bones where it is associated with dense, fusiform, reactive sclerosis. Less often, it may be cancellous, where reactive osteosclerosis is usually less intense and may be distant from the lesion. Cancellous lesions are frequently intraarticular (most often in the hip) and may be associated with synovitis and joint effusion. Rarely, osteoid osteomas occur in a subperiosteal location. Patients are usually young, and there is a strong male predominance. Pain is the most common symptom. Radiographs of patients with cortical osteoid osteoma are often diagnostic. Intraarticular lesions, however, may be subtle, and scintigraphy may be required to locate the lesion for subsequent computed tomography (CT). CT is useful to identify and precisely locate the lesion and to provide guidance for percutaneous localization or treatment. PMID- 1887123 TI - Ultrasound case of the day. Peritransplant lymphocele, accompanied by pulsus alternans. PMID- 1887124 TI - General case of the day. Nodular amyloidosis of the lung. PMID- 1887125 TI - Allergen avoidance in childhood asthma. PMID- 1887126 TI - Endobronchial tuberculosis mimicking lung cancer in elderly patients. AB - We report four elderly patients with cough who were referred with the presumptive diagnosis of bronchial carcinoma based on chest X-ray and the macroscopic view on fibreoptic bronchoscopy, but whose final diagnosis was endobronchial tuberculosis. Chest X-ray showed atypical pulmonary infiltrates in three patients, but was normal in one. Bronchoscopic examination revealed ulcerative and/or stenotic lesions. Endobronchial tuberculosis should be considered in differential diagnosis, especially in the elderly. PMID- 1887127 TI - Tuberculin survey in the Eastern Province of Saudi Arabia. AB - We present the results of the Mantoux test (5 units tuberculin) survey in the Eastern Province of Saudi Arabia, which was conducted as part of a nationwide epidemiological survey of tuberculosis. A total of 1105 subjects were screened out of whom 630 gave a history of BCG vaccination in the past and 363 were BCG negative. Among BCG-negative children aged 5-14 years, only 5% had a positive Mantoux, a rate lower than most Third World countries but higher than developed countries were under 2% of children are tuberculin reactors. This calls for continuation of free treatment of active cases and increased efforts towards screening of contacts. The results also vindicate the current policy of giving BCG vaccine at birth and probably indicates the need to revaccinate at school leaving age, in accordance with WHO recommendations. Tuberculin reactivity rose steeply with age (32% at age 15-24 and 72% at age 45-64 years) indicating the presence of a large pool of subjects at risk of breaking into active disease. Finally, 71% (201/283) of children aged 5-14 years who had received BCG vaccine at birth, reacted negatively to the Mantoux test. This supports the findings of previous studies that in the majority of subjects, BCG-induced tuberculin sensitivity fades a few years after vaccination. PMID- 1887128 TI - Paediatric parapneumonic effusions: a review of 16 cases. AB - Over a 2-year period, 16 children with parapneumonic effusions were identified at the Royal Alexandra Hospital for Sick Children, Brighton. The case notes of these children were retrospectively reviewed. The presenting symptoms caused diagnostic confusion in two children resulting in negative laparotomies. Isolation of the infecting organism from the parapneumonic group was comparable to other authors, 6 out of 16 patients (53%); however, when the yield from pleural aspirates is compared, there was only one positive culture out of six (17%). Possibilities for improving this disappointing isolation rate are discussed. Two children with the longest history of symptoms and shortest chest drainage time had long term problems. Diagnostic tap, which carries little risk, and drainage, if required, should be performed early. PMID- 1887129 TI - Analysis of breath sounds in normal and asthmatic children and adults using computer digitized airway phonopneumography (CDAP). AB - Analysis of breath sounds using the stethoscope is a major part of physicians evaluation of their patients. However, the use of a stethoscope is often inadequate to give quantitative measurements of the clinical state of the individual. In this study a modification of a previously described computer analysis of breath sounds was used to measure sound intensity levels in both normal and asthmatic children who, in most cases, were unable to perform pulmonary function. The intensity levels were derived using a microcomputer-based program that digitizes audio signals and calculates energy values at 25-ms intervals throughout each signal. There were statistical differences between mean intensity levels for normal breath sounds in children between 2 and 6 years and the mean intensity levels for wheezing sounds in the same age group, as well as wheezing sounds in asthmatic patients over the age of 8 years (P less than 0.002). Also, the mean intensity levels for normal breath sounds could be clearly differentiated from intensity levels for other sounds from the chest, including heart sounds and voice sounds. Thus, computer digitized airway phonopneumography (CDAP) proved to be a reproducible, quantifiable method for demonstrating airway obstruction in those children and patients unable to perform pulmonary function testing. PMID- 1887130 TI - Continuous positive airway pressure ventilation for respiratory failure associated with Pneumocystis carinii pneumonia. AB - The value of continuous positive airway pressure (CPAP) ventilation via a tight fitting face mask was assessed in eight HIV-1 antibody-positive patients with Pneumocystis carinii pneumonia who were in hypoxaemic respiratory failure. All patients were conscious, able to protect their airway and not hypercapnic. Treatment was effective in seven patients. Prior to CPAP, mean (range) arterial oxygen tension was 6.7 (4.7-10.5) kPa in seven patients breathing oxygen via a face mask (FiO2 = 0.6), 6.1 kPa in one patient breathing room air and rose to 9.9 (6.8-12.8) kPa with CPAP (FiO2 = 0.6 and PEEP = 1.3 kPa in six patients and 2.6 kPa in one patient); the mean increase in PaO2 was 3.1 kPa (P less than 0.02). These seven patients experienced a rapid reduction in dyspnoea and their respiratory rate fell from a mean of 40 breaths min-1 to 32 breaths min-1 (P less than 0.001). One patient deteriorated rapidly on CPAP and died: no other complications were seen with this technique. CPAP was continued for a mean of 4.5 days and the seven responders all survived the episode of P. carinii pneumonia. We conclude that mask CPAP provides an effective means of improving oxygenation in severely hypoxaemic patients with P. carinii pneumonia. PMID- 1887132 TI - Late onset pulmonary metastases from 'benign' mucinous ovarian cystadenomata. PMID- 1887131 TI - Inflammatory markers in cystic fibrosis. AB - Plasma neutrophil elastase-alpha 1 antiproteinase complex, lactoferrin and C reactive protein (CRP) were determined over a 15-month period in 26 patients with cystic fibrosis, of whom 21 were chronically infected with Pseudomonas aeruginosa. Median concentrations of both neutrophil products and CRP were greater in patients who were clinically stable than in healthy subjects without cystic fibrosis. CRP concentrations increased further at the onset of symptomatic exacerbations. Thirty-five courses of intravenous antibiotics and 22 courses of oral ciprofloxacin were reviewed and revealed similar improvements in clinical scores and lung function tests for both forms of treatment. Intravenous antibiotics reduced the plasma concentrations of both neutrophil products and CRP, while oral ciprofloxacin only significantly reduced the concentration of neutrophil elastase-alpha 1 antiproteinase complex. Plasma concentrations of inflammatory markers were significantly greater in exacerbations associated with fever and leukocytosis. Statistical modelling demonstrated negative within patient relationships between lung function and both CRP and lactoferrin, and positive relationships between the three inflammatory markers. Neutrophil granule products and CRP reflect the pulmonary inflammatory state in cystic fibrosis and may be of value in monitoring treatment. PMID- 1887133 TI - Ocular toxicity of ethambutol. PMID- 1887134 TI - Smoking cessation in hospital patients given repeated advice plus nicotine or placebo chewing gum. PMID- 1887135 TI - The use of inhaled formoterol in asthma. PMID- 1887136 TI - Restrictive pulmonary disorders. PMID- 1887137 TI - Lymphocytes in asthma. PMID- 1887138 TI - [The practice of nursing administration]. PMID- 1887139 TI - [Leadership and communication]. AB - This study deals with the concepts of leadership and the role of the leader in communicating with his team. It stresses communication's concepts, process and its importance to built all organizations. PMID- 1887140 TI - [The preparation for self-care of the diabetic client and his family]. AB - Partial report, quanti-qualitative of action-research developed in the ward test/ambulatory of a University Hospital, extensive to home; integrating students, teachers and nursing team. OBJECTIVE: to establish standards to integrate hospital/community, seeking the man in the home circle, oppose the recovery/rehabilitation and the integration to work/society, considering the problems in the home/work and put into practice the proposition of the SUDS with extension to the hospital/community actions. Home visits raising the home conditions, family and/or community, consolidating their participation in the process. During the hospital stay nursing care was oriented to conduct the participation and realization of the care by the client and relatives happening the same in the ambulatory probation. PMID- 1887141 TI - [The hospitalization experience explained by the child himself]. AB - This study, was accomplished with 20 school-age children hospitalized in pediatric units. The goals were: how children expressed their perception of the illness and the hospitalization; what sources were available to obtain knowledge about their experience of illness and hospitalization and what were their interest and concerns. PMID- 1887142 TI - [The integration of teaching and care: the transformation of the quality of teaching and of community health care via praxeological management]. PMID- 1887143 TI - [The work of the surgical unit nurse in Brazil (the decade of the '80s)]. AB - From the view of the historical and dialectic materialism of the nurse work as a social practice insured in the Brasilian capitalistic mode of production of the eighties, these study, through the decomposition of the surgical room nursing work in his three essential elements, search to point the necessary comprehension not only of these components but, mainly, for the agreement of his superstructural relations through the Brazilian mode of production in sense of, with these reflective praxis, search a synthesis, within what I have (what the operating room nurse work is) and, what I want, synthesis which will allow a new practice. PMID- 1887144 TI - [Nursing and research in Brazil]. AB - The brazilian nursing in relation to research presented an important development in the last few years, with a quantitative improvement in the last decade. The brazilian researchers are concentrated in its majority among the faculty members and in the Southeast of Brazil. There are eight graduate university centers with several knowledge areas of concentration at master level. The doctoral level programs are all in the Southeast. There are resources available in research financial agencies for nursing, however the demand is still incipient. The Brazilian Nursing Association has tried to implement procedures which aim the development of researchers in nursing. PMID- 1887145 TI - [Nursing care for patients with changes in the elimination of tracheobronchial secretions]. AB - This research discuss the respiratory defense mechanisms with special attention to the cilio-muco activity and cough reflex. It shows the alteration in these mechanisms, the follow pulmonary complications and the nurse role in the care with this kind of patients. PMID- 1887146 TI - [Reflections on the nurse's responsibility in administering drugs]. AB - This paper is intended to stress the nurse's responsibility in therapeutic drugs administration, mainly as related to her (or his) Knowledge of the pharmacological principles involved in drugs prescriptions. The Nursing Process regarding drug and client/patient assessment is herein presented as well as some example of nursing diagnosis. Planning and evaluation of nursing actions are also discussed and other issues are stressed that require a high degree of reasoning and research in the field. PMID- 1887147 TI - Primary biliary cirrhosis in the elderly. AB - Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease with onset about menopause. To investigate its clinical features and the natural history in relation to age, we examined 86 consecutive patients with PBC (81 F, 5 M); 70 were less than 65 years (mean age 48 years) and 16 greater than 65 years (mean age 69 years). All patients were followed-up for 6 months-16 years (mean 4 years). Histological stage at presentation was comparable in the two groups, but among aged PBC subjects there was a significantly higher prevalence of asymptomatic patients (56% vs 24%, p less than 0.001). No significant differences were observed in the biochemical indices and immunological abnormalities. Survival curves showed no significant differences in PBC according to the age. Mortality was observed only in the group less than 65 years (15/70, 21.4%). In conclusion, the large proportion of asymptomatic subjects in the elderly PBC patients accounts for the similar survival in the two groups of patients. PMID- 1887148 TI - Non-Hodgkin's lymphoma of the elderly. Prognostic factors and outcome. AB - The initial features and prognosis of non-Hodgkin's lymphoma (NHL) of the elderly have been variously evaluated in literature. We have examined 190 patients with NHL: most of them received induction therapies containing vincristine, cyclophosphamide and/or anthracyclines (CVP, CHOP, CEOP); age at diagnosis was over 65 for 62 of them (32.63%). Elderly patients had a lower rate of complete remissions, a shorter duration of complete remissions and, consequently, a poorer overall survival. In our patients, prognosis was related also with stage, histology (according to Working Formulation, WF) and performance status at the diagnosis. Elderly patient had not a significantly increased incidence of these unfavourable prognostic factors at the onset. However, patients aged 65 or more received lower doses of drugs during induction therapy (cyclophosphamide: 81%; vincristine: 73%; anthracyclines: 22% of patients under 55). Patients aged 55-65 had induction therapies of intermediate intensity; also proportion of complete remissions and survival were intermediate between the two other groups. Haematological toxicity appeared the most important cause of these reductions: in fact nadirs of neutrophils and platelets during induction therapy were similar in the 3 groups in spite of the different intensity of treatment. Even if statistical correlations are not possible, the incidence of infections has been higher in the elderly. PMID- 1887149 TI - [The duodenoscopic picture in adult celiac disease]. AB - The duodenal endoscopic pictures were studied in 12 adult coeliacs patients, aged between 18 and 76 years, mean age 41.9 +/- 17.6 yrs. All patients carried out D xylose absorption test, antigliadin IgA antibodies and distal duodenum biopsy. The more frequent endoscopic picture was the disappearance of Kerckring's folds; nevertheless in 5 patients the loss of Kerckring's folds was associated with duodenal mucosa irregularity. We believe that in future the knowledge of this new endoscopic picture will be useful in coeliac's disease diagnosis. PMID- 1887150 TI - [Ulcerative colitis in hairy cell leukemia. A case report]. AB - Hairy cell leukemia (HCL) is a chronic lymphoproliferative disorder sometimes affected by autoimmune complications. The use of human recombinant alpha interferon (alpha-IFN) in the therapy of this disease may also lead to the development or the exacerbation of autoimmune pathology. We report the case of a HCL patient, treated with IFN, who developed ulcerative colitis two years later and we discuss the possible correlations of these two entities. PMID- 1887151 TI - An association of primary hyperparathyroidism and non medullary thyroid carcinoma. AB - A 40-year-old woman was admitted because of long-lasting asymptomatic hypercalcaemia. About 2 years earlier she underwent thyroidectomy and further 131 I therapy because of well-differentiated non medullary thyroid carcinoma. On admission biochemical data and hormonal values (serum calcium, serum phosphorus, i-PTH) were consistent with primary hyperparathyroidism; ultrasonography, computed tomography, thallium-technetium scintiscanning disclosed right paratracheal mass; on surgical procedure a right parathyroid adenoma was removed. The coexistence of non medullary thyroid carcinoma and primary hyperparathyroidism is rare: the prior 131 I therapy might be linked to subsequent development of parathyroid adenoma. PMID- 1887152 TI - Hyperkalaemia during infusion of hyperosmolar amino acid solutions enriched with branched chain amino acids. Report of two cases. AB - We report two cases of unexplained hyperkalaemia during infusion of amino acid solutions enriched with branched chain amino acids. The increase in potassium levels developed 24 hours after starting infusion and normalization was obtained within 24 hours after stopping infusion. Acidosis, acute renal failure, concomitant cell destruction and haemolysis were excluded; antialdosteronic diuretics were not given. The authors hypothesize that hyperkalaemia could be due to a sudden increase in plasmatic osmolality caused by the hyperosmolarity (900 mOsm/l) of the solution, not counterbalanced by adequate ADH release owing to malfunctioning of hypothalamic osmoreceptors. At present this hypothesis is lacking in experimental proofs. PMID- 1887153 TI - [Histiocytic necrotizing lymphadenitis or Kikuchi and Fujimoto's disease. A case report]. AB - We describe a case of necrotizing histiocytic lymphadenitis or Kikuchi and Fujimoto disease, a rare lymphadenopathy of unknown etiology usually striking young women. It was formerly described in Japan, and subsequently in other countries and in Italy as an anatomo-clinical entity. The disease has a favourable prognosis, therefore it has to be considered differently from other lymphadenopathies with severe prognosis whose anatomo-pathological differential features were analyzed by the authors. The case here observed differs from other cases described in literature because of the presence of a perilymphadenitic component. PMID- 1887154 TI - [Headache in Horton's disease: the clinical picture and physiopathogenetic mechanisms]. AB - Headache is no doubt one of the most frequent symptom in Horton's disease. Nevertheless it has neither received a clear definition nor it has been studied in its pathogenetic aspects. The authors report 32 cases of Horton's disease in acute phase with arteritic localizations in different areas. Among them 24 (75%) had headache which appeared with different features from case to case. The authors identify 3 different kinds of headache, all recognizable in the secondary medical forms: epicritic headache (the most frequent), deep headache and generic headache (the rarest). The characters and the pathogenetic mechanisms of each form are also described. PMID- 1887155 TI - The eosinophilia-myalgia syndrome and related disorders. AB - The recognition of the eosinophilia-myalgia syndrome associated with L-tryptophan in the United States during 1989 as a disorder resembling the previously described 1981 toxic oil syndrome of Spain has established an increased level of consciousness regarding drug and toxin associated diseases. Both of these disorders were characterized by the development of acute and chronic multisystem features that parallel many idiopathic connective tissue diseases. Common manifestations have included generalized myalgias, fever, transient pulmonary infiltrates, and xerostomia during the early months followed by late stage neuromuscular and cutaneous disease. The most conspicuous laboratory abnormality was a peripheral eosinophilia. One of the most striking clinical findings has been scleroderma-like skin disease manifesting as diffuse fasciitis or hidebound induration. A sensory neuropathy and proximal myopathy in association with skin thickening have established these syndromes as chronic disabling diseases for many of their victims. Mononuclear perimysial and epineurial infiltrates have been distinctive pathological findings. Although the etiology of the eosinophilia myalgia syndrome and the toxic oil syndrome are unknown, there is epidemiologic evidence to support the presence of contaminants in L-tryptophan and rapeseed oil, respectively, as the causative agents. No therapy has been demonstrated to arrest the evolution of the chronic sequelae in either disorder. PMID- 1887156 TI - [The interleukin-2 receptor]. AB - The interleukins comprise a class of hormones that have a definite known secondary and tertiary structure under physiologic conditions. The interleukin-2 is the leader in T cell differentiation. The interleukin-2 acts via interaction with high affinity, cell bound receptors (IL-2R). High affinity IL-2 receptors are constructed by cooperative binding of IL-2 to both the low affinity (55-Kd chain) and intermediate affinity (75-Kd chain) binding sites. The light (55-Kd) chain of these heterodimeric receptors is identified by monoclonal antibodies as TAC antigen. A soluble form of these receptors is released in the serum and it can be assayed by ELISA. Extraordinarily high levels of IL-2R are characteristic of hairy cell leukaemia. Smaller increases of IL-2R have been reported in other haematological conditions as well as in other disorders including AIDS, organ transplantation etc. Moreover, we have recently demonstrated that IL-2R is elevated in lung cancer. PMID- 1887157 TI - [The application of photopheresis in the therapy of cancerous and autoimmune diseases]. AB - Photopheresis is an extracorporeal form of immunotherapy, recently approved by the FDA for the treatment of cutaneous T-cell lymphoma. During photopheresis lymphocytes are collected from the patients by leukapheresis and after exposure to psoralens and UVA reinfused to the host. The reinfused cells induce an immunological reaction against the neoplastic cells that seems to be clone specific. 37 CTCL patients have been initially treated; 1/4 showed a complete remission, 1/4 did not answer to the therapy and 1/2 showed a clinical improvement without complete remission. The best responders were patients in erythrodermic stage, particularly when photopheresis had been started early. The association with methotrexate induced a complete clinical remission in the cases with a partial answer to photopheresis. The average survival of patients treated with photopheresis was around 50 weeks in comparison with the Mycosis Fungoides Study Group data reporting for the same type of patients a 30 weeks survival using conventional therapies. Photopheresis has been recently used in the rejection control after heart transplantation and in the treatment of AIDS and several autoimmune diseases as pemphigus, sclerodermia, rheumatoid arthritis, LES. The preliminary therapeutic results are very encouraging for a larger use of photopheresis in the treatment of T cell mediated diseases. PMID- 1887158 TI - [The ambulatory medical treatment of colonic diverticulitis. An open clinico endoscopic-histological study with rifaximin, a nonaminoglycoside enteric antibiotic]. AB - Twenty patients with mild acute diverticulitis of the colon were treated with rifaximine 400 mg b.i.d. per os per 10 days. From a clinical point of view, spontaneous and evoked abdominal pain, diarrhoea, nausea, leukocytosis and hyperthermia resulted in marked significant reduction at the end of treatment, as compared to the basal data (P less than 0.01). A significant reduction of the peridiverticular oedema, mucosal redness, submucosal haemorrhage and diffuse granular pattern was observed endoscopically at the end of treatment (P less than 0.05). Only a trend toward degrees of vasodilation and submucosa hemorrhage was observed from the histological point of view. No side-effect was observed during and after the treatment period. PMID- 1887159 TI - [Comments on the "chronic fatigue syndrome"]. PMID- 1887160 TI - [Is it possible to establish an objective criterion for evaluating scientific publications?]. PMID- 1887161 TI - Introduction: the host-microbial interface. PMID- 1887162 TI - The host-microbial interface. PMID- 1887163 TI - Parasitic adherence and host responses in the development of Pneumocystis carinii pneumonia. AB - Pneumocystis carinii pneumonia is a common cause of morbidity and mortality in patients with acquired immunodeficiency syndrome. In this article, the parasitic and host factors contributing to the pathophysiology of P carinii pneumonia will be reviewed. In particular, P carinii adherence to alveolar epithelial cells plays a central role in the development of pneumonia. Potential mechanisms mediating this attachment include cell surface glycoproteins, exogenous fibronectin and components of the parasitic cytoskeleton. Host factors contributing to respiratory impairment also have been recently evaluated. Inflammatory responses, aimed at ridding the lung of P carinii, may result in further deterioration of respiratory function. A better understanding of the host parasite relationship in P carinii pneumonia eventually will lead to the development of novel therapies for this increasingly common respiratory disorder. PMID- 1887164 TI - Aspergillosis and lung defenses. AB - Aspergillosis refers to any of the illnesses caused by fungi that are members of the genus Aspergillus. The diseases range from allergic responses that occur in the absence of fungal growth (asthma, hypersensitivity pneumonitis), to colonization with or without an allergic component (allergic bronchopulmonary aspergillosis, aspergilloma, saprophytic involvement of infarcted tissue), to invasion and destruction of lung parenchyma (invasive aspergillosis, chronic necrotizing pulmonary aspergillosis). The development of lung infection and/or disease depends on interaction among three factors: the characteristics of the fungus (virulence factors), the status of host defense mechanisms, and the type of exposure. The purpose of this article is to review these factors and their relationship to the clinical syndromes of aspergillosis. PMID- 1887165 TI - Factors promoting pathogenicity of influenza virus. AB - Each year, influenza infections cause significant morbidity and mortality in spite of intense research and control efforts. Virus is transmitted primarily by aerosolization of respiratory secretions, and infection can be caused by a small number of viral particles. Following inhalation, virus is deposited on the mucous blanket overlying the target epithelial cell. Mucociliary clearance is the normal mechanism by which deposited particulates are removed; immunoglobulins at the airway surface also play an important role in neutralization of virus. Influenza virus is very efficient at overcoming host defenses, primarily due to the function of two surface glycoproteins, hemagglutinin and neuraminidase. Both glycoproteins have antigenic sites that undergo variation. Hemagglutinin also contains cell binding sites, while neuraminidase prevents interference of mucins with cell binding. Although other factors may contribute to infectivity of the influenza virus, antigenic variation of hemagglutinin is the single most important factor. Influenza vaccination is the most effective means presently available to decrease the attack rate and impact of this infection on society. PMID- 1887166 TI - Pertussis: an old disease in a new era. AB - Pertussis has a worldwide incidence of 51,000,000 cases per year with a 1% case fatality rate and primarily affects young children. Despite the availability of an effective whole-cell pertussis vaccine, pertussis has reemerged as a significant cause of human morbidity in areas where pertussis vaccine programs have ceased because of vaccine safety concerns. The search for new vaccines without side effects has stimulated an intensive study of virulence determinants of Bordetella pertussis. As a result of this research, virulence genes of B pertussis and factors that regulate these genes have been identified and characterized. The molecular characterization of the virulence determinants of B pertussis has helped to elucidate the basis of some of the clinical observations that characterize disease caused by B pertussis. It appears that host factors may potentially determine whether virulence genes are expressed. It is now possible to construct mutants of B pertussis that are deficient in individual virulence determinants. The era of the molecular Koch's postulates is upon us, and the roles of individual virulence factors in disease pathogenesis can be studied. In this article, issues concerning immunity to pertussis, safety of whole-cell vaccine, and virulence factors of B pertussis are considered. The molecular Koch's postulates as they relate to testing prospective virulence factors in pertussis infection model systems will be presented. The mucosal environment as a potential modulator of virulence factors will be addressed. PMID- 1887167 TI - Pulmonary toxoplasmosis. AB - Symptomatic pulmonary toxoplasmosis is a relatively rare disease process, although the lung is frequently infected with the causative agent Toxoplasma gondii. Acute infection resulting in diffuse pneumonia is most likely in the immunosuppressed transplant recipient, and reinfection pneumonia occurs in this patient population as well as in patients with acquired immunodeficiency syndrome. The authors discuss the methods this protozoan uses to invade cells, to evade host defenses, and to cause tissue necrosis. The epidemiology of the disease relates directly to an inability to mount the effective cell-mediated immunity needed to keep the tissue cysts from undergoing effective replication into destructive tachyzoites. Alveolar macrophages and gamma interferon have been shown to be two important effector mechanisms in this control. Outcome is directly related to the ability to make an early diagnosis, which requires increased awareness of this disease in the patient populations at risk. PMID- 1887168 TI - Legionella pneumophila: denizen of defenders. AB - Legionella pneumophila, the causative agent of legionellosis, is an intracellular parasite of human monocytic cells and neutrophils. The life cycle of Legionella within phagocytic cells is distinct from that of other bacterial pathogens. Adherence of L pneumophila to phagocytes is mediated by attachment of complement proteins to the Legionella cell surface, followed by binding to complement receptors of phagocytes. Opsonized Legionella also may enter phagocytes after engagement of the Fc receptors. Within the host cell, the parasites reside in a membrane-bound vacuole that does not fuse with lysosomes. Activation of mononuclear phagocytes by the cell-mediated immune system serves to limit intracellular bacterial growth. Polymorphonuclear leukocytes are better at killing L pneumophila than are macrophages. However, Legionella also can invade and parasitize granulocytes. Although significant progress has been made in understanding some aspects of the pathogenesis of legionellosis, we know very little about the mechanisms by which these facultative intracellular parasites avoid killing by host defense mechanisms. This is an important area for future research and should lead to a better understanding of host-parasite interactions. PMID- 1887169 TI - [A new concept: elastodontics]. PMID- 1887170 TI - [Encouraging cooperation of adolescents in their orthodontic treatment, or the practice of effective communication]. PMID- 1887171 TI - [Non-radiographic cephalometry: the Dolphin Imaging System]. PMID- 1887172 TI - [Research, practice and information]. PMID- 1887173 TI - [Comparative evaluation of two means of investigating craniomandibular dysfunction: axiography and magnetic resonance imaging]. PMID- 1887174 TI - [Effect of dental plaque acids on composites used in orthodontics: in vitro study]. PMID- 1887175 TI - [Orthodontics and cleft lip and palate]. PMID- 1887176 TI - [Thermo-formed splints for finishing, expansion, distalizing and prevention of thumbsucking]. PMID- 1887177 TI - [Idiopathic myelofibrosis]. AB - The authors make a review of recent data in the literature and compare them to their own cases between 1983 and 1988. They analyzed eight patients with idiopathic myelofibrosis confirmed with bone marrow biopsy of the posterior iliac wrist with Jamshidi's needle. Most patients were between 55 and 60 years old (5 male and 3 female). Major symptoms were weakness and bleeding (6/8 cases), weight loss and bone distress (4/8 cases). In general, physical signs were splenomegaly and anemia (7/8 cases), hepatomegaly (5/8 cases), and jaundice (2/8 cases). Laboratory features were variable. Most cases were diagnosed in an advanced stage of the disease. Therapy with busulfan, prednisone, oxymetholone and radiotherapy of the spleen was used alone or in combination to relieve compressive abdominal symptoms. This review shows that idiopathic myelofibrosis should be included in the differential diagnosis of patients with hepatosplenomegaly and anemia. PMID- 1887178 TI - [Comparison between pelvic endovaginal and transabdominal sonography in the measurement of the uterus and ovaries]. AB - PURPOSE: this study compares endovaginal sonography to the transabdominal ultrasound in terms of their accuracy in the measurement of the uterus and ovaries. TYPE: prospective study. PLACE: Sao Paulo, SP, Brazil. PATIENTS: Forty nine women were included in the study in order to assess the clinical suspicion of pelvic mass or because they had vaginal bleeding in initial gestation. The patients were submitted to transabdominal sonography and later to endovaginal ultrasound (5.0mHz transducer). Uterus and ovaries were measured. RESULTS: the volume of 27 left and 29 right ovaries was measured. Echographic hysterometry was performed in 49 women and statistically compared. The Wilcoxon rank sum test failed to show any significant difference between the two sonographic techniques in the measurement of uterus and ovary volume. CONCLUSIONS: endovaginal ultrasound presents several advantages over transabdominal scanning. Patient's discomfort is minimum because vesical repletion is not called for. Imaging resolution is magnified and morphologic details are clearly seen because the transducer is in close contact with pelvic viscera. Results do not evidence any significant difference in the uterine measurements with either method, and the statistical difference in ovarian volume was not significant either. PMID- 1887179 TI - [Ileal loop perforation caused by tuberculosis in patients with the acquired immunodeficiency syndrome]. AB - This clinical and surgical study was performed in a Public Government Hospital with the purpose of investigating the etiology and treatment of acute perforative abdomen in AIDS patients, particularly in the case of intestinal tuberculosis. The authors describe the cases of two young male AIDS patients with acute abdomen in which surgery revealed intestinal ileal perforation due to tuberculosis. One of the patients did not survive due to his poor post-operative condition. The other case had a better evolution and was submitted to outpatient care. The immediate surgery with occlusion of the perforation and biopsy of the lesion permitted to arrive at the etiology and contributed to the good evolution of the second patient. CONCLUSION: Literature indicates cytomegalovirus as the main cause of intestinal perforation in AIDS patients. In this study, etiology was tuberculous and this is probably an important cause of acute perforative abdomen in our AIDS patients due to the general prevalence of tuberculosis in AIDS patients in Brazil and in other developing countries. PMID- 1887180 TI - [Effects of food restriction on the protein and electrolyte composition in the liver and muscles of rats]. AB - Protein and electrolyte disturbances in hepatic and muscle tissues are related to trauma, sepsis, or short term starvation or semistarvation. The consequences of a prolonged semistarvation are poorly understood. For five weeks, male adult rats were offered 50% of the diet until they had a weight loss of 40%, after which protein and electrolyte (Ca++, Mg++, Zn++, Na+, K+) changes in the liver and soleus and extensorum digitorum longus muscles were analyzed. There was a significant weight loss after 5 weeks of semistarvation. Hepatic protein and serum albumin were not changed, but the authors observed a significant muscle protein depletion. A fall in Zn++ levels in the blood was accompanied by a rise in muscle and liver concentrations. The rise in Ca++ and Mg++ concentration in blood and in the muscles might be related to the enhanced proteolysis. Results suggest that the early changes of protein and electrolyte metabolism at tissue level with semistarvation impair muscular and hepatic functions as they delay adequate response to trauma and infection. PMID- 1887181 TI - [Gastrin changes in the gastric antrum G-cells and in serum gastrin levels after 80% jejunoileal resection in rats]. AB - A study was made of the changes in the cell population producing gastrin of the gastric antrum in rats submitted to resection of 80% of jejunum-ileum. Ninety days after surgery, the animals were killed after a 12 hour nightly fast and the gastric antrum was removed with the objective of specific histological preparations (PAP method) in order to count the G-cells and the blood was taken for serum doses of gastrin. An optical microscope was used to count the cells using a histometric integraded ocular of 42 points and the counting of 10 fields of each histological cut, and the radioimmunoassay method of double antibody was used for the seric dosing of gastrin. Histometry showed a significant drop in the G-cell population of the antrum of enterectomized animals when compared to the control group. Average percentage of G-cells found were 17.55% in the control group and 7.99% in the enterectomized ones. Blood dosing of hormone showed a significant increase of gastrin in the enterectomized animals when compared to controls. Average value of gastrin dosing the control group was 110 Pg/ml and 170 Pg/ml in enterectomized animals. Therefore, the present study permits to conclude that after resection of 80% of jejunum-ileum, there was a decrease in the G-cell population with gastrin in the gastric antrum even in the presence of increased serum gastrin. PMID- 1887182 TI - [Psychiatric aspects of chronic pain syndrome]. AB - PURPOSE: to propose a systematization of the conditions in which chronic pain and psychiatric disturbances are concomitantly found, such systematization being based on the distinction between primarily psychiatric conditions and primarily neurologic conditions that have pain as their common central symptom. TYPE: literature review. CONCLUSIONS: systematization of psychiatric disturbances presented as complaints of pain allows the physician to be more specific in the therapeutic scheme for each patient. Nowadays pain should be seen as an important symptom by the psychiatrist, as it points towards some entities in the psychiatric nosography of which treatment has been well established; the general practitioner should always be alert to think about a concomitant psychiatric disturbance that could justify the chronic nature of the complaint. PMID- 1887183 TI - [Lipoid cell tumor of the ovary]. AB - The authors show the clinical and histopathological difficulties for the diagnosis of a rare ovarian tumor in a 13 year old girl who had a bone disease called enchondromatosis, and the adequate treatment for this case. Laparotomy was performed with unilateral salpingo-oophorectomy of the left ovary after a detailed study to detect the origin of the pelvic mass, the patient, who had metrorrhagia and pains in the lower abdomen. Three years after surgery, the patient was once again seen in the outpatient clinic with regular catamenia, requesting some oral contraceptives because she had started sexual activity. The authors conclude that the lipid cell tumor of the ovary is difficult to classify and diagnose, and that it is normally benign, and that treatment for this type of tumor, specially in youngsters, in whom one should be concerned with maintaining menstrual and reproductive function, is the unilateral oophorectomy. PMID- 1887185 TI - A unique approach to dental laboratory management. PMID- 1887184 TI - [Transient cerebral ischemic attack and amaurosis fugax caused by carotid ergotism]. PMID- 1887186 TI - Porcelain shoulder technique using visible light activated resin. PMID- 1887187 TI - Passive fits achieved for fixed detachable implant restorations. PMID- 1887188 TI - Preventing the risk factors in childhood learning impairment. PMID- 1887190 TI - The role of the physician in early intervention screening for infants and toddlers. AB - Research conducted over the past decade with infants and preschool children has confirmed the positive outcomes of early intervention. As a result, an urgent need now exists to develop strategies which accurately identify children in need of such services. Information derived from a comprehensive research base suggests that developmental surveillance models hold the most promise for accurately identifying developmentally disabled and vulnerable young children; and moreover, that physicians must assume a critical role in such models. Research also indicates that if such models are to be effective, they must be multivariate, child and family focused, and undertaken more than once. PMID- 1887189 TI - Perinatal care and learning disorders: a community view. PMID- 1887191 TI - Traditions and innovations: a community-based approach to substance abuse prevention. PMID- 1887192 TI - Childhood lead poisoning: a Rhode Island perspective. AB - The Rhode Island Department of Health recognizes lead exposure as the State's most important environmental health problem. Historically, the program has relied on secondary prevention strategies consisting primarily of screening, case finding, limited environmental intervention and medical management. While secondary prevention of lead toxicity identifies existing cases in a preclinical stage, it does not prevent exposure to lead hazards. The sources of lead exposure need to be appropriately identified and abated if exposures and re-exposures are to be prevented. Because of the ubiquity of lead and practical limitations of available resources, a large number of children with elevated blood lead levels will continue to go unscreened and undetected unless more effective screening strategies are implemented. Present reliance on the free erythrocyte protoporphyrin (FEP) test as a primary screening tool is recognized as an insensitive way to identify children with blood lead levels below 40 micrograms %. With growing evidence of toxicity and long term health effects associated with blood lead levels in the range between 10 and 40 micrograms %, blood lead analysis will need to become part of the routine method of screening. PMID- 1887193 TI - Aging 2000: pursuing progressive care for Rhode Island's elderly. PMID- 1887194 TI - Low birth weight in Rhode Island: the survival of the tiniest. PMID- 1887195 TI - [Loss of psychic autoactivation syndrome: bilateral lacunae of the neostriatum. Clinico-radiological study of 2 cases]. AB - In two patients with lack of spontaneous activity and emotionality, without dementia or depression and in absence of other neurologic signs, the "athymormia syndrome" has been diagnosed. CT scan and MRI showed bilateral symmetrical lesions in basal ganglia. We discuss the possible pathophysiological basis of the syndrome and the recent data about the functional connections among basal ganglia, frontal cortex and limbic system. PMID- 1887196 TI - Quadriceps myopathy: report of a late onset sporadic case. AB - The Authors describe the case of a 44 year-old man whose familial and personal histories were negative for muscular diseases. The patient complained slowly progressive wasting and weakness localized to the quadriceps muscles. The bioptic study of the gastrocnemius and the quadriceps showed dystrophic changes, confirming that muscular dystrophy closely localized to quadriceps is of rare occurrence. Muscles other than quadriceps can often be involved by the same pathology even if the clinical signs continue to be localized to the quadriceps muscles for many years. PMID- 1887197 TI - Multiple learning tasks in patients with ideomotor apraxia. AB - The Authors studied a group of patients with ideomotor apraxia (LBD+) to verify if these patients had some difficulties in multiple learning tasks in respect to non-apraxic patients and normal control subjects. All five groups were submitted to gesture learning task, motor skill learning task, supra-span (Corsi) learning task. The results indicate that learning difficulties were present in LBD+ patients, as demonstrated by their low performance in gesture sequence, motor skill and score of block-tapping supra-span task. This fact may be seen as a basic learning deficit and therefore linked to memory impairment. On the other hand, this could be tied to an aspecific more diffuse deterioration of attention if we consider that our apraxic patients had a greater cerebral lesion than non apraxic patients. PMID- 1887198 TI - [Tolosa-Hunt syndrome. TC findings in a case]. AB - The Tolosa Hunt Syndrome is a rare neurological disease. It can be the consequence of a number of processes localized in the cavernous sinus or near to it. The diagnosis has been until now a diagnosis of exclusion, even if the phlebography can give more informations. Recently the possibility of demonstrating the process has been obtained by the high resolution CT scan that can show peculiar findings as in the case that we are describing. PMID- 1887199 TI - [De-afferented state syndrome (locked-in syndrome) following sudden cervical sprain trauma during a karate training session]. AB - The paper describes a patient, who developed a "locked-in" syndrome following a cervical trauma occurred during karate training. The neurological picture was determined by an ischemic lesion of the ventral pontine region. The pathophysiological aspects concerning the association between cervical trauma and athletic activities are discussed. PMID- 1887200 TI - A family with hereditary intracerebral cavernous angiomas. AB - There are a very few reports in literature of inherited intracerebral cavernous angiomas. The majority of them are Mexican-American families. In some of the reported families autosomal dominant transmission is suggested. We report a family in which three members of three consecutive generations were proven to have multiple intracerebral cavernous malformations, without involvement of skin, eyes, or other viscera. An autosomal dominant mode of inheritance is clearly suggested. PMID- 1887201 TI - Patient and caregiver can be stricken by drug dependency. PMID- 1887202 TI - The senate adds bite to the CDC bark. PMID- 1887203 TI - Our HMO offers more than medical care. PMID- 1887204 TI - Adding insult to injury. PMID- 1887205 TI - Traumatic amputation. PMID- 1887206 TI - Wandering atrial pacemaker. PMID- 1887209 TI - When ethics and orders conflict. PMID- 1887207 TI - What's wrong with this patient? PMID- 1887208 TI - Pulmonary embolism. Preventing a disaster. PMID- 1887210 TI - Patient privacy vs. the risk of disease to caregivers. PMID- 1887211 TI - Using seat belts can help save your own life. PMID- 1887212 TI - Another way to keep postpartum and nursery units safe. PMID- 1887213 TI - Family history and pathophysiological mechanisms of primary hypertension. Studies in non-hypertensive young men with positive and negative family histories of hypertension. AB - In an attempt to explore pathophysiological mechanisms relevant for the development for future primary hypertension, we investigated young normotensive men with positive family histories of hypertension (PFH) regarding blood pressure, body weight, systemic and renal haemodynamics as well as cardiovascular hormones and sodium homeostasis. Sixteen subjects with PFH and thirteen controls with negative family histories (NFH), matched for age and body weight were investigated at age 31 and after five years. Blood pressure and heart rate did not differ between the two groups at the first or follow-up examination. At follow-up body weight had increased and a positive correlation between blood pressure and body mass index was found in subjects with PFH, while subjects with NFH had unchanged blood pressure and body weight. Initially, intraerythrocyte sodium content was increased in subjects with PFH, however, at follow-up intraerythrocyte sodium content did not differ between the two groups. At follow up systemic and renal haemodynamics and sodium homeostasis were investigated in fifteen subjects with PFH and in twenty-nine controls matched for age (36 +/- 5 year) and with NFH. The control group was divided into one group matched for body mass index (n = 15) and one group with normal body mass index (n = 14). Blood pressure and central venous pressure were measured during bolus injections of phenylephrine and during an acute saline/fluid load (1000ml 0.9% NaCl within 10 min). Renal haemodynamics and blood pressure were measured during low doses (0.1 and 0.5 ng/min/kg) continuous infusions of angiotensin II (AII). At baseline blood pressure, body weight and sodium excretion were higher in subjects with PFH and matched controls as compared with lean controls. Calf and forearm haemodynamics (pletysmography), plasma catecholamines, plasma renin activity, angiotensin II, aldosterone, blood volume and erythrocyte sodium efflux rate constant did not differ between the three groups. Circulating atrial natriuretic peptide was higher in subjects with PFH than in the two control groups. In subjects with PFH there was a negative correlation between renal sodium excretion at baseline and the ouabain-sensitive sodium efflux rate constant. During the acute saline/fluid load central venous pressure and systolic blood pressure increased more and venous vascular compliance (ml/mmHg/kg) was reduced in PFH. Atrial natriuretic peptide release and renal sodium excretion were blunted during saline/fluid load in subjects with PFH as compared with the two control groups. Renal blood flow and renal vascular resistance did not differ at baseline. Glomerular filtration rate was somewhat higher in PFH.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1887214 TI - Wright's shifting balance theory: an experimental study. AB - Experimental confirmation of Wright's shifting balance theory of evolution, one of the most comprehensive theories of adaptive evolution, is presented. The theory is regarded by many as a cornerstone of modern evolutionary thought, but there has been little direct empirical evidence supporting it. Some of its underlying assumptions are viewed as contradictory, and the existence and efficacy of the theory's fundamental adaptive process, interdemic selection, is the focus of controversy. Interdemic selection was imposed on large arrays of laboratory populations of the flour beetle Tribolium castaneum in the manner described by Wright: the differential dispersion of individuals from demes of high fitness into demes of low fitness. A significant increase in average fitness was observed in the experimental arrays when compared to control populations with equivalent but random migration rates. The response was not proportional to the selection differential: The largest response occurred with interdemic selection every two generations rather than every generation or every three generations. The results indicate that the interdemic phase of Wright's shifting balance theory can increase average fitness and suggest that gene interactions are involved in the observed response. PMID- 1887215 TI - Medium effects in antibody-catalyzed reactions. AB - Catalytic antibody technology has been used to explore the contribution of medium effects to the overall rate of an enzyme-catalyzed reaction. An antibody generated against a derivative of 2-acetamido-1,5-napthalenedisulfonate efficiently catalyzes the decarboxylation of 5-nitro-3-carboxybenzisoxazole. This unimolecular reaction is not susceptible to general acid-base catalysis but is highly sensitive to microenvironment; thus, it provides a simple chemical model for biologically important decarboxylations. The 10(4)-fold rate acceleration observed for the antibody reflects the kinetic advantage of the low-dielectric environment of the binding pocket acting to destabilize the substrate by desolvation and to stabilize the charge-delocalized transition state through dispersion interactions. These results are pertinent to an understanding of solvent effects in enzymic reactions in general and suggest approaches for developing antibody catalysts for numerous other reactions that involve large changes in charge distribution as the reaction coordinate is traversed. PMID- 1887216 TI - Differential phosphorylation of the transcription factor Oct1 during the cell cycle. AB - Orderly progression through the somatic cell division cycle is accompanied by phase-specific transcription of a variety of different genes. During S phase, transcription of mammalian histone H2B genes requires a specific promoter element and its cognate transcription factor Oct1 (OTF1). A possible mechanism for regulating histone H2B transcription during the cell cycle is direct modulation of Oct1 activity by phase-specific posttranslational modifications. Analysis of Oct1 during progression through the cell cycle revealed a complex temporal program of phosphorylation. A p34cdc2-related protein kinase that is active during mitosis may be responsible for one mitotic phosphorylation of Oct1. However, the temporally controlled appearance of Oct1 phosphopeptides suggests the involvement of multiple kinases and phosphatases. These results support the idea that cell cycle-regulated transcription factors may be direct substrates for phase-specific regulatory enzymes. PMID- 1887217 TI - Induction of inflammatory arthropathy resembling rheumatoid arthritis in mice transgenic for HTLV-I. AB - Human T cell leukemia virus type-I (HTLV-I) is the etiologic agent of adult T cell leukemia and has also been suggested to be involved in other diseases such as chronic arthritis or myelopathy. To elucidate pathological roles of the virus in disease, transgenic mice were produced that carry the HTLV-I genome. At 2 to 3 months of age, many of the mice developed chronic arthritis resembling rheumatoid arthritis. Synovial and periarticular inflammation with articular erosion caused by invasion of granulation tissues were marked. These observations suggest a possibility that HTLV-I is one of the etiologic agents of chronic arthritis in humans. PMID- 1887219 TI - A difference in hypothalamic structure between heterosexual and homosexual men. AB - The anterior hypothalamus of the brain participates in the regulation of male typical sexual behavior. The volumes of four cell groups in this region [interstitial nuclei of the anterior hypothalamus (INAH) 1, 2, 3, and 4] were measured in postmortem tissue from three subject groups: women, men who were presumed to be heterosexual, and homosexual men. No differences were found between the groups in the volumes of INAH 1, 2, or 4. As has been reported previously, INAH 3 was more than twice as large in the heterosexual men as in the women. It was also, however, more than twice as large in the heterosexual men as in the homosexual men. This finding indicates that INAH is dimorphic with sexual orientation, at least in men, and suggests that sexual orientation has a biological substrate. PMID- 1887218 TI - HRR25, a putative protein kinase from budding yeast: association with repair of damaged DNA. AB - In simple eukaryotes, protein kinases regulate mitotic and meiotic cell cycles, the response to polypeptide pheromones, and the initiation of nuclear DNA synthesis. The protein HRR25 from the budding yeast Saccharomyces cerevisiae was defined by the mutation hrr25-1. This mutation resulted in sensitivity to continuous expression of the HO double-strand endonuclease, to methyl methanesulfonate, and to x-irradiation. Homozygotes of hrr25-1 were unable to sporulate and disruption and deletion of HRR25 interfered with mitotic and meiotic cell division. Sequence analysis revealed two distinctive regions in the protein. The NH2-terminus of HRR25 contains the hallmark features of protein kinases, whereas the COOH-terminus is rich in proline and glutamine. Mutations in HRR25 at conserved residues found in all protein kinases inactivated the gene, and these mutants exhibited the hrr25 null phenotypes. Taken together, the hrr25 mutant phenotypes and the features of the gene product indicate that HRR25 is a distinctive member of the protein kinase superfamily. PMID- 1887220 TI - Forensic DNA tests and Hardy-Weinberg equilibrium. PMID- 1887221 TI - Toxic chemicals and toxic laws. PMID- 1887222 TI - Immortal sequence. PMID- 1887223 TI - Children and divorce. PMID- 1887224 TI - Patent validity. PMID- 1887225 TI - Is homosexuality biological? PMID- 1887226 TI - The brain as "sexual organ". PMID- 1887227 TI - Is "gender gap" narrowing? PMID- 1887228 TI - Trimming research flagship's sails. PMID- 1887229 TI - Heeding the call of the wild. PMID- 1887230 TI - Was Wright right? PMID- 1887231 TI - Animal choice behavior and the evolution of cognitive architecture. AB - Animals process sensory information according to specific computational rules and, subsequently, form representations of their environments that form the basis for decisions and choices. The specific computational rules used by organisms will often be evolutionarily adaptive by generating higher probabilities of survival, reproduction, and resource acquisition. Experiments with enclosed colonies of bumblebees constrained to foraging on artificial flowers suggest that the bumblebee's cognitive architecture is designed to efficiently exploit floral resources from spatially structured environments given limits on memory and the neuronal processing of information. A non-linear relationship between the biomechanics of nectar extraction and rates of net energetic gain by individual bees may account for sensitivities to both the arithmetic mean and variance in reward distributions in flowers. Heuristic rules that lead to efficient resource exploitation may also lead to subjective misperception of likelihoods. Subjective probability formation may then be viewed as a problem in pattern recognition subject to specific sampling schemes and memory constraints. PMID- 1887232 TI - Name of the game? PMID- 1887233 TI - Can OSI withstand a scientific backlash? PMID- 1887234 TI - Bernadine Healy: a new leadership style at NIH. PMID- 1887235 TI - UK diabetics plan insulin suit. PMID- 1887236 TI - Polymer scientists work to beef up biosensors. PMID- 1887237 TI - Specific DNA binding by c-Myb: evidence for a double helix-turn-helix-related motif. AB - The c-Myb protein is a sequence-specific DNA binding protein that activates transcription in hematopoietic cells. Three imperfect repeats (R1, R2, and R3) that contain regularly spaced tryptophan residues form the DNA binding domain of c-Myb. A fragment of c-Myb that contained the R2 and R3 regions bound specifically to a DNA sequence recognized by c-Myb plus ten additional base pairs at the 3' end of the element. The R2R3 fragment was predicted to contain two consecutive helix-turn-helix (HTH) motifs with unconventional turns. Mutagenesis of amino acids in R2R3 at positions that correspond to DNA-contacting amino acids in other HTH-containing proteins abolished specific DNA binding without affecting nonspecific DNA interactions. PMID- 1887238 TI - Conserved sequence and structural elements in the HIV-1 principal neutralizing determinant: further clarifications. PMID- 1887239 TI - SDNA statement on rural health nursing. PMID- 1887240 TI - Verbal abuse in the emergency department. PMID- 1887241 TI - The time has come for differentiated practice. PMID- 1887243 TI - Role of bone marrow transplantation in sickle cell anemia. PMID- 1887242 TI - Nurse practitioners and clinical nurse specialists reimbursement in rural areas. PMID- 1887244 TI - Introduction to a symposium on sickle cell anemia: current results of comprehensive care and the evolving role of bone marrow transplantation. PMID- 1887245 TI - Sickle cell anemia: beta s-gene-cluster haplotypes as prognostic indicators of vital organ failure. AB - Identification of the beta s-gene-cluster haplotype and alpha-gene status provide a useful tool to improve the possibility for early detection in high-risk SS patients. The DNA polymorphisms of the beta s-gene-cluster modify the clinical course in sickle cell anemia especially as it involves the risk of end-stage organ failure of the kidney, lung, and brain. In both Africa and America, the CAR beta s haplotype increases the risk of developing irreversible complications at an early age. The degree of anemia, the Hb F concentration, and the preservation (or lack thereof) of G gamma Hb F is haplotype dependent and correlates with the overall clinical course of the patient. Further modulation of the clinical course by the coinheritance of alpha-thalassemia-2 tends to decrease the risk of soft tissue organ failure but increases the risk of osteonecrosis. A single individual can be expected to fit into the overall pattern. Some sickle related illness will eventually occur in all patients. In the presence of a Senegal haplotype, the patient's health is better, with the CAR haplotype it is always worse; severity is intermediate in the Benin. These genetic markers can be used to identify the endangered patient before the onset of irreversible major organ failure. The high risk SS patient with a CAR chromosome or one who is homozygous Ben without alpha thalassemia-2 should be monitored closely for evidence of vasculopathy-induced microinfarction of the brain, kidneys, or lungs. Such a patient needs preventive therapy before suffering a major hemisphere stroke, losing kidney function, or developing cor pulmonale secondary to restrictive lung disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1887246 TI - What do we know about the clinical course of sickle cell disease? PMID- 1887247 TI - Stroke in sickle cell disease: demographic, clinical, and therapeutic considerations. PMID- 1887248 TI - Comprehensive care in sickle cell disease: its impact on morbidity and mortality. PMID- 1887249 TI - Sickle cell diseases in the 1990s: the need for active and preventive intervention. PMID- 1887250 TI - The dilemma of marrow transplantation in sickle cell anemia. PMID- 1887251 TI - Marrow transplantation for severe aplastic anemia and thalassemia major. PMID- 1887252 TI - Bone marrow transplantation for sickle cell anemia. PMID- 1887253 TI - Chronic graft-versus-host disease and other late complications of bone marrow transplantation. PMID- 1887254 TI - The pros and cons of bone marrow transplantation for sickle cell anemia. PMID- 1887255 TI - Bone marrow transplantation for sickle cell anemia: summarizing comments. PMID- 1887256 TI - Replication of hepatitis B and delta viruses: appearance of viral mutants. PMID- 1887257 TI - A 20-year-old man with persistent aminotransferase elevations. AB - Through intravenous drug abuse, this 20-year-old man contracted chronic active hepatitis due to hepatitis D superinfection of hepatitis B. The correct diagnosis, made after a hiatus of 20 years, awaited advances in the understanding of viral hepatitis, the discovery of the hepatitis D virus, and the development of immunostaining techniques that could be applied to his liver biopsy specimen. The case illustrates how immunoperoxidase staining may be done retrospectively and may be particularly useful in diagnosis of individual cases where serologic testing is not available or possible, as well as in scientific surveys of HBV and HDV infection. Since staining for HBcAg and HDAg can provide clinically useful information not available by other methods, it should be considered as a part of the assessment of the liver biopsy in every patient with HBV infection. PMID- 1887258 TI - Prenatal diagnosis of beta-thalassemia. AB - In this review I have discussed the state of our knowledge of the molecular basis of beta-thalassemia and its prenatal diagnosis. Improved but more complicated genetic counselling is now available as a result of our increased knowledge of the effects of various defects in the beta-globin gene. Our knowledge of the heterogenous molecular basis of the thalassemia syndromes has become very impressive and it is hoped that effective therapy will soon follow. However, for the present, prevention of the birth of affected children is the most effective means of reducing the suffering associated with the thalassemia syndromes, and prevention of this type is succeeding in many parts of the world, including North America. PMID- 1887259 TI - Hemostasis in the perinatal period: approach to the diagnosis of coagulation disorders. AB - A wide range of hemostatic disorders may complicate the clinical course of the mother or fetus during pregnancy and the perinatal period. Given the potentially life-threatening implications of hemorrhage or thrombosis, it is important to evaluate these clinical emergencies with an organized approach to the diagnosis of the pertinent derangement and its etiology in order to institute corrective action promptly. Therapeutic interventions are outside the scope of this presentation; however, it is evident that an efficient and precise diagnosis is the first step toward effective, corrective action. The three elements of the hemostatic system that have been presented, blood vessels, platelets, and plasma proteins, provide a logical framework for initiating the hemostatic evaluation and interpreting screening hemostasis tests. Optimum patient management is rewarding, since many of the disorders discussed in this article are of brief duration, improving after the peripuerium. In contrast, the manifestations of hemorrhage may lead to life-long complications. PMID- 1887260 TI - Neonatal alloimmune thrombocytopenia. PMID- 1887261 TI - The role of intravenous immunoglobulin in the treatment and prevention of neonatal bacterial infection. PMID- 1887262 TI - Neonatal testing for hemoglobinopathies. PMID- 1887263 TI - The role of cell-wall deficient bacteria (L-forms; sphaeroplasts) in fish diseases. PMID- 1887264 TI - Effects of aquatic environmental stress on enteric bacterial pathogens. PMID- 1887265 TI - Survival and growth of Legionella species in the environment. PMID- 1887266 TI - Aeromonads and their significance as potential pathogens in water. PMID- 1887267 TI - Mycobacteria in the environment. PMID- 1887268 TI - Implications for the release of genetically engineered organisms. PMID- 1887269 TI - Allergenic and toxigenic micro-organisms in houses. PMID- 1887270 TI - Selective isolation methods for fish pathogens. PMID- 1887271 TI - Bacterial pathogens in domesticated animals and their environment. PMID- 1887272 TI - Viral and bacterial pathogens of insects. PMID- 1887273 TI - Sources and survival of campylobacters: relevance to enteritis and the food industry. PMID- 1887274 TI - Women's perspectives on chronic illness: ethnicity, ideology and restructuring of life. AB - This inquiry into the lives of women living with a chronic illness brings to attention the complex processes that frame the existential meanings of illness. Data from immigrant Chinese and Anglo-Canadian women with diabetes are used to show that illness is constructed in a complex social, political and economic nexus. When the circumstances of women's lives are examined, styles of managing illness that could be attributed to ethnicity, become recognizable as pragmatic ways of dealing with the harsh realities of material existence. It is argued that the trends toward individualizing social problems, and shifting the responsibility for caretaking from the state to the individual, obfuscate the social context of illness, and exclude the socially disadvantaged from adequate health care. PMID- 1887275 TI - Coping with an ileostomy. AB - This paper reports the results of a study of persons who had undergone surgery to cure the disease ulcerative colitis. All subjects had had their colon removed and were left with an incontinent surgically constructed anus on their abdomen, called an ileostomy. The ways in which ex-patients cope with some of the consequences of surgery are described. The data were collected using semi structured interviews, which were analysed qualitatively. PMID- 1887276 TI - Employee and job attributes as predictors of absenteeism in a national sample of workers: the importance of health and dangerous working conditions. AB - This study reports on research which looks for employee and job characteristics which correlate with absenteeism. A large cross-sectional national probability sample of workers employed for at least 20 hr per week is analyzed (n = 1308). The dependent variable is the number of self-reported absences during the past 14 days. Thirty-seven independent variables are considered. Ordinary Least Squares (multiple regressions), two-limit Tobits, and two-part models are used to assess the statistical and practical significance of possible covariates. Statistically significant predictors included health variables such as being overweight, complaining of insomnia, and hazardous working conditions; job characteristics such as inflexible house; and personal variables such as being a mother with small children. Variables reflecting dangerous working conditions appear to be the strongest correlates of absenteeism. Notable variables which do not predict absenteeism include age, race, wages, and job satisfaction. Future research should direct attention toward workers' health and working conditions as covariates of absenteeism, since they are strongly significant in this study and have been neglected by most absenteeism investigators. PMID- 1887277 TI - Discrepant legacies: premature mortality in two industrial towns. AB - Previous research has indicated that, while large parts of Middlesbrough and Sunderland appear to be equally severely deprived, premature mortality in the early 1980s was substantially worse in Middlesbrough. Postcoded mortality data from 1975 to 1986 were assembled, to ascertain whether this disparity reflected a temporary or consistent difference between these two towns. In addition, to enable detailed consideration of the differentials in premature mortality, data on cause of death for 23 cause-groups were assembled for the 6-year period 1978 to 1983. The results show that, throughout the 12-year period, death rates below the age of 65 years in Middlesbrough's poorer areas consistently exceeded death rates in comparable areas of Sunderland by a large margin. This disparity is demonstrated to affect both sexes and all age-groups below 65. Middlesbrough's excess mortality was evident for most causes of death (19 out of 22 causes among men, and 16 out of 23 causes among women), with cerebrovascular disease and genitourinary malignancy among women being the only major exceptions. Possible explanations for this wide difference are considered. The conclusions of research in Lancashire, suggesting that the antecedents of present differences may be found in infant health disparities from the 1920s and 1930s, do not seem to apply in this instance. The possibility that unmeasured differences in levels of poverty or the suddenness of its onset may be contributory influences remains problematic. Individual lifestyle is not considered a plausible explanation, but possible differences in the provision and use of health services between the two towns are thought worthy of closer investigation. It is also suggested that environmental differences, in terms of the built environment and atmospheric pollutants require closer scrutiny. PMID- 1887278 TI - Ayurveda, malaria and the indigenous herbal tradition in Sri Lanka. AB - Using key informants and available records, the way in which inhabitants of purana villages in Nuwarakalaviya, Sri Lanka coped with malaria during the pre DDT era is examined. This study found that the Nuwarakalaviya peasants responded to endemic malaria through a localized herbal tradition, which was to some extent independent of the scholarly ayurveda system common to the whole of South Asia. The relevant herbal tradition, consisting of a combination of antiparasite and antivector strategies using locally available natural resources, represented an effective adaptation to the local ecosystem. PMID- 1887279 TI - General practitioners' subjective experience of surgery workload. AB - General practitioners (GPs) in the U.K. frequently cite heavy workload as a major source of work-related stress. However, there is little direct evidence either to support this claim or to suggest whether the source of this stress lies in the amount, or rather the type, of work undertaken. The present paper uses a within subjects design to address these issues in the surgery context. Over a two-week period three GPs gave ratings of subjective workload following each of their surgeries (N = 20-23). Correlational analysis showed a wide range of surgery characteristics to predict the GPs' reactions, including the length of surgeries, the number of consultations, the number of re-presentations, and the number of follow-ups and investigations requested. The GPs' perceptions of their patients (e.g. in terms of their health status and the appropriateness of the consultation), in contrast, did not emerge as significant predictors. The results of multiple regression analyses, however, revealed that most of the first-order effects could be accounted for by surgery length. Thus while the study supported the hypothesised link between the overall level of surgery work demands and the subjective experience of workload, it failed to confirm any consistent additional effects of the type of work involved. It was also found that as the length of surgeries increased, the GPs were more likely to arrange follow-up appointments. The implications of the present findings are therefore two-fold.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1887280 TI - Tswana medicine in interaction with biomedicine. AB - The purpose of this paper is twofold: to describe Tswana medicine as a system of thought and to show how traditional medical roles are acted out in the encounter with Western biomedicine. I want to draw attention to the contrast between the intellectual systems of African traditional thought and Western science as applied to health and illness (medicine). I do not argue that biomedicine is more open and adaptable to change than folk medicine, or vice versa. Rather, I want to show that both integration ('openness'), as well as rejection ('closeness'), occur when Tswana medicine meets biomedicine. How do the Botswana make sense of a new body of knowledge and ideas of contagion in a context of medical pluralism? How are medical roles adapted to the situation of medical pluralism and the predicaments that flow from such a situation. In conclusion I will briefly discuss some of the elements that may determine the future outcome of the integrative health policy: Is it possible to obtain mutual understanding and cooperation among the various practitioners--in the context of medical pluralism- when their knowledge is built on such different medical explanations and modes of though as those of biomedicine and folk medicine? PMID- 1887281 TI - Effects of social relationships on survival for women with breast cancer: a prospective study. AB - In this study we examine the relationship between a woman's social contexts at the time of diagnosis and her chances of having survived breast cancer four years later. A cohort of 133 women were followed prospectively after initial diagnosis and treatment and data were obtained from a questionnaire mailed soon after diagnosis and from hospital charts. Using multivariate methods to examine predictors of survival, two clinical factors, pathologic nodal status and clinical stage of disease, were significantly associated with survival. In addition we found significant and independent effects on survival of: number of supportive friends, number of supportive persons, whether the woman worked, whether she was unmarried, the extent of contact with friends and the size of her social network. Thus, the woman's social context, particularly contexts of friendship and work outside the home, are statistically important for survival. Using existing literature, further data analyses and interviews with some survivors, we speculate on the ways in which social contexts may influence survival and suggest research methods suitable to this question. PMID- 1887282 TI - Promoting traditional medicine in Ethiopia: a brief historical review of government policy. AB - Past and current official policy toward Ethiopian traditional medicine is reviewed. To facilitate the objective assessment of official policy, the nature and historical origins of Ethiopian traditional medicine is examined briefly. It is noted that there is no single system of traditional medicine in Ethiopia, even though themes that are common to the many cultural groups constituting the society have been evolving. Common to most systems of Ethiopian traditional medicine are the interdigitation of 'mystical' and 'natural' explanations of ill health and other misfortune and the holistic approach employed in dealing with illness and other personal misfortune. It is also noted that since the 1974 change of government in Ethiopia, official attitude toward the promotion and development of traditional medicine appears to have become more positive, especially, after the adoption of the Primary Health Care strategy in 1978. While this is true as far as official statements are concerned, in actual practice there continues to be considerable uncertainty about the interpretation and implementation of Government policy. It is suggested that misconceptions regarding the nature and role of traditional medicine in Ethiopian society will have to be corrected if appropriate plans and strategies are to be formulated. PMID- 1887283 TI - Dental care of institutionalized elderly in Singapore. AB - Previous studies have identified considerable barriers to dental care and unmet dental needs among institutionalized elderly. This study examined physical and financial arrangements for dental care of institutionalized elderly in Singapore. Chief administrators of the 68 homes for the elderly in Singapore were interviewed. Results showed that 48 homes (70.7%) assumed responsibility for arranging dental care and providing access to treatment facilities for its ambulant residents while only 33 homes (48.5%) had similar arrangements for semi- and non-ambulant residents. Four of the homes (5.9%) reported having in-house dental facilities while the rest arranged for its residents to be treated either in public dental facilities (44.2%) or in private dental offices (20.6%). Type of sponsorship of the homes and ambulatory status were closely associated with the type of arrangement for dental care. Over 64.6% of homes (44) required residents to be fully responsible for the costs of their dental care. The availability of subsidies for residents' dental costs was found to be associated with the type of sponsorship and type of arrangement for care. Lack of physical access and financial constraints were found to be potential problems in the utilization of dental services in this population group. PMID- 1887284 TI - Age at first experience of intercourse among Norwegian adolescents: a lifestyle perspective. AB - Age at first intercourse among Norwegian adolescents was studied by means of survival analysis. The data stemmed from a nation-wide survey of 3000 Norwegian adolescents aged 17-19, yielding a response rate of 61.8%. Median age at first intercourse was 17.3 years among girls and 18.0 years among boys. By means of Cox regression analysis associations between age at onset of intercourse and some correlates were estimated. Age at first intercourse was significantly associated with educational aspirations, smoking behaviour, alcohol consumption, peer affiliation, and frequency of visiting a discotheque. These inter-relationships confirm that age at onset of intercourse comprise an important indicator of the lifestyle of an individual. In order to influence sexual behaviour of adolescents it may thus be appropriate to employ health promotion activities focusing upon environmental and structural factors, as a supplement to traditional methods of sex education. PMID- 1887285 TI - Ad Hoc Research Committee on Brain Death and Organ Transplantation. PMID- 1887286 TI - Social medicine in China. PMID- 1887287 TI - A role for cognitive-behavioural strategies in schizophrenia? PMID- 1887289 TI - Associations with social networks, social support, health status and psychiatric morbidity in three samples of elderly people. AB - The effects of social network structure, support and physical health status on psychiatric morbidity were investigated among 1415 people over retirement age who took part in three independent but comparable surveys in London (urban area) and Essex (semi rural area). Multivariate analysis showed that the model explained between 14.3% and 28.6% of the variation in psychiatric morbidity in the three samples. Poor health status was a more powerful predictor of psychiatric morbidity than the social network variables. Age and sex contributed little to the model. The model was strongest among the two samples of Hackney respondents. PMID- 1887288 TI - Socio-economic status, employment and neurosis. AB - In a national sample of over 3,000 36-year-olds, neurosis was more prevalent in men of lower status as assessed by housing tenure but not occupational class, education or personal income. Symptoms were more frequent in the unemployed, especially those not seeking work. In women, rates did not differ by husband's occupational class but were higher for those in rented accommodation, with unskilled manual jobs, without paid employment, with poor qualifications and with unemployed husbands, the strength of associations being dependent upon family structure. Many of these associations were reduced or eliminated by adjustment for reported financial hardship. Accounts of mental health problems in unemployed men and in married women (especially with children) may have underestimated the importance of financial circumstances. PMID- 1887290 TI - Using longitudinal data to estimate nonresponse bias. AB - In a recent survey of depressive symptoms among former prisoners of war, longitudinal data were used to estimate nonresponse bias. A predictive model was fitted to the data of current respondents and then was used to predict the scores of nonrespondents who had earlier provided similar convariate data. This analysis showed that, despite differences between respondents and nonrespondents in age, education, and severity of treatment during captivity, differences between the observed scores of respondents and the predicted scores of nonrespondents were small. For an estimation of the overall impact of nonresponse bias, revised estimates for the entire sample were calculated by combining observed data from respondents and predicted data for nonrespondents; the revised estimates differed little from those for respondents alone. PMID- 1887291 TI - Multidimensional properties of the General Health Questionnaire. AB - This analysis re-examines the factor structure of the 12-item GHQ for a large Australian sample of young people. It shows that oblique factor rotation better approaches the criterion of simple structure, and allows separate components of the GHQ to be identified and measured using factor scores. When the performance of these separate factors is compared with composite Likert scores, it is found that they do not behave uniformly in response to outside variables, both in cross sectional and longitudinal analyses. These results suggest that there are advantages to be gained by using the multidimensional properties of the GHQ as well as a single severity score. The additional information this yields can provide new insights into the nature of psychiatric impairment within and between samples. PMID- 1887293 TI - [Effects of physical exercise on the parameters of carbohydrate metabolism in patients with type 2 diabetes mellitus during rehabilitative treatment]. AB - The evidence obtained by the authors supports literature data on a beneficial effect of muscular exercise on carbohydrate metabolism in diabetics. It is thought necessary to control sharp fluctuations of glycemia. Provided these are mild and associated with lowered insulinemia, patients with non-insulin-dependent diabetes mellitus could be recommended to continue training. PMID- 1887292 TI - Psychotropic drug use in an urban primary care clinic. AB - The prevalence and pattern of psychotropic drug use was investigated in an urban walk-in clinic in Nigeria during the course of a two-stage epidemiological survey. A total of 14.9% of the patients were using psychotropic drugs, with almost all the users taking anxiolytics. There was no significant sex difference in the prevalence of drug taking. Almost half of the users had been on the drug for over 12 months. Increasing age was associated with psychotropic drug taking in females while being married had a similar association in males. While increasing score on the GHQ-12 was associated with drug taking, over two-thirds of patients with DSM-IIIR disorders identified during the second-stage interview were not taking any psychotropic drug. PMID- 1887294 TI - [Changes in the spectrum of blood lipids in patients with renal amyloidosis]. PMID- 1887295 TI - [Characteristics of serum lipid state in women with premature failure of the ovarian function]. AB - The evidence obtained supports referring women with ovarian amenorrhea and gonadal dysgenesis to a high-risk group for atherosclerosis and cardiovascular diseases. This fact dictates inclusion of the diagnosis of atherogenic dyslipoproteinemia into the complex of check-up measures for women with early nonoperative ovarian amenorrhea as well as prophylaxis of cardiovascular disorders. PMID- 1887296 TI - [Cytochemical characteristics of lymphocytes in peptic ulcer under various states of acid secreting function of the stomach]. AB - Metabolic activity of lymphocytes was evaluated in ulcer patients with different acid-production function. Measurement of succinic dehydrogenase and alpha glycerophosphate dehydrogenase of the mitochondria showed that acid production activity brought about variations in the activity of alpha-glycerophosphate dehydrogenase suggesting activation of a reserve path of the cell energy supply. The data obtained on the strain of the local defence and repair processes in gastric mucosa of patients with ulcer running with hyperacidity especially upon cicatrization of the lesion, provide a basis for the disease outcome. PMID- 1887297 TI - [Use of an immunologic test in confirming diagnosis of breast cancer]. PMID- 1887298 TI - [Ultrasound monitoring during healing process in drained postoperative wound]. AB - The diagnosis of subclinical suppuration in operative wounds after removal of drainage tubes can be established after ultrasonic investigation of the wound. The ultrasound findings permit control of postoperative purulent complications by taking therapeutic measures to evacuate suppurative wound contents. PMID- 1887299 TI - [Emergency pulmonology]. PMID- 1887300 TI - [Chest pain of noncoronary origin]. PMID- 1887302 TI - [Theory and practice of infrastructure reorganization of the entire system of public health]. PMID- 1887301 TI - [Assessment of quality of life in internal medicine]. PMID- 1887303 TI - [Role of medical and occupational expertise in staged rehabilitation of postmyocardial infarct patients]. PMID- 1887304 TI - [Effects of adelphan-esidrex on hemodynamic indexes at rest and character of their changes during exercise tests]. PMID- 1887305 TI - [The cardiovascular system in polycythemia vera]. PMID- 1887306 TI - [Use of a two-component analysis of myocardial contractility during rehabilitation of patients with ischemic heart disease]. PMID- 1887308 TI - [Degree of objectivity in the assessment of the effect of antiulcer agents]. PMID- 1887307 TI - [Care of the focus of lesion during various stages of the surgical treatment of chronic osteomyelitis]. PMID- 1887309 TI - [Use of autotransfusion of ultraviolet irradiated blood in severe forms of viral hepatitis B]. PMID- 1887310 TI - [Ultrasonic study in the determination of the degree of extensiveness of cancer in the proximal part of the stomach]. PMID- 1887311 TI - [Use of primary plastic surgery of the tendons of the deep flexors in combined injuries of vascular-nerve fascicles of the fingers]. PMID- 1887312 TI - [Function of kidney transplant in the early post-transplantation period]. PMID- 1887313 TI - [Barotherapy in the treatment of acute renal failure in crush syndrome]. PMID- 1887314 TI - [Prevention of obstetric hemorrhage]. PMID- 1887315 TI - [Diastolic changes in isolated stenosis of the pulmonary artery after correction of valvular defect]. AB - Intracardiac hemodynamics and myocardial function were studied in 20 patients surgically treated for a valve defect. All the patients developed isolated stenosis of the pulmonary artery. It is emphasized that an early postoperative period in relevant correction proceeds with diastolic impairments. Some factors affecting the degree of the diastolic filling of the right ventricle upon the defect correction are determined. Adequate therapy of the disorders in proposed. PMID- 1887316 TI - [Digestive and absorptive function of the intestine in abdominal typhus]. PMID- 1887317 TI - [Use of immunofluorescence method in the diagnosis and study of pathogenesis of acute dysentery]. PMID- 1887318 TI - [A case of successful use of captopril in severe congestive heart failure]. PMID- 1887319 TI - [Long-term course of adenocarcinoma of the transverse colon]. PMID- 1887320 TI - [Coronary-right atrial shunt with formation of aneurysm of the atrial septum in a 4-year-old child]. PMID- 1887321 TI - [Factors related to mortality in neonatal tetanus in the rural area of Jalisco]. AB - In this article, we report the results of a survey taken in towns with less than 2,500 inhabitants in the rural tetanigenic zone of the State of Jalisco. The purpose was to know the Infant Mortality Rate (IMR), the Neonatal Tetanus Mortality Rate (NTMR), the incidence of neonatal tetanus, and a partial register of these indicators, as well as the identification of the risk factors associated with fatalities from this disease. The sampling was multistaged with random selection of the conglomerates. The results were as follows: 75 deaths in children of less than one year of age with an IMR of 34.7 per 1,000 Live Births Registered (LBR), 40 deaths in those of less than 29 days old (Neonatal Mortality Rate of 18.5 per 1,000 LBR), eight deaths by neonatal tetanus (NTMR of 3.7 per 1,000 LBR), the estimated annual incidence rate of neonatal tetanus was 4.6 per 1,000 LBR, and the proportion of neonatal deaths due to tetanus was 20 per cent. The main factors studied which were statistically found to be significantly associated with the mortality rate from neonatal tetanus were: a maternal history of two or more prior child deaths having an Odds Ratio (OR) of seven; the existence of cramped living conditions greater than 3.5 persons per room (OR = 7.93); maternal illiteracy (OR = 7.22); and birth at the home (OR = 17.89). When the logistics model was used to control some of the misleading factors and obtain adjusted OR estimates, place of birth and the maternal history or two or more prior child deaths were found to be significant. PMID- 1887322 TI - [The creation of the state of adversity. Regulation and social policy in Latin America]. AB - This work presents some recent information that documents the regressive effects of the external debt, and deals with promoting reflection upon the so called State of Adversity, which by means of political regulation, (and contrary to the classic State of Welfare), is being created in the Region. This work also puts forth some points which seem inevitable in the still open debate regarding the growth-equity relationship in Latin America. Firstly, a revision of the principal social and economic indicators is made beginning with the early years of this decade ('90). Secondly, the inserted patterns of regulation are synthetically introduced, and some of the results and problems are analyzed. Thirdly, and as an effect of successive regulation implementations that have not accomplished the desired macroeconomic equilibrium (nor economic growth), the creation of the State of Adversity is analyzed by means of looking at the disintegration that takes place in the incipient State of Wellbeing that exists in the Region. This disjointed situation brings with it a significant reduction in the quantity and quality of social services in the public sector and the exclusion of an even greater segment of the population (those pertaining to a characteristically subsistence level economy and low productivity). We do not deny the need for regulation, nor do we believe that it should encompass the social sectors, where significant financial allotments geared to combat suffering and poverty, at the same time, have not been unable to avoid their expansion (not to mention the total elimination of same). The problem here lies not in regulation, but in what kind of regulation and for whom. Finally, this work presents some ideas on mixed economy of wellbeing which could recover the potential of the public sector and market by urging a collective macroregulation that would make possible the needed investments to finance a growth with greater social integration. PMID- 1887323 TI - [Economic development and health]. AB - The purpose of this work is to examine the relationship between economic development and the population's level of health. Consequently, we will establish a comparison between Mexico and other countries in various stages of development. The interrelationship between economic development and health is a complex problem which is little understood, even though it is acknowledged that at increased levels of economic development the levels of health of a population will also increase. These considerations can be taken into account when we accept the fact that the health conditions in industrialized countries are generally better than the health conditions in non-industrialized countries. In the case of Mexico, the problems relating to social disparities due to the type of economic development are reflected in the country's level of health. Poor health conditions and the deterioration of health services in Mexico, based on international references, are matters that must be resolved by means of a clear political decision accompanied by the appropriate corresponding resources so that the strategies put forth by the National Health Program (1989-1994) can be carried out. PMID- 1887324 TI - [Tijuana: endemic zone of Coccidioides immitis infection]. AB - To consider a geographical zone as endemic for Coccidioidomycosis, three requisites are necessary: 1. isolation of the causal agent, Coccidioides immitis, from the environment, 2. a prevalence of infection among the population of that area of at least 5%, and 3. the demonstration of clinical cases of coccidioidomycosis in that population. There are no previous reports on the endemicity of Coccidioidomycosis in Tijuana, Baja California, mexico. We are reporting: a) the isolation of the causal agent, C. immitis from the environment, b) the results of a survey with intradermal antigens of the fungus, with a prevalence of infection among 1 128 healthy subjects of 10%, and c) the incidence of this systemic mycosis among the population of patients of the Tijuana General Hospital during a three-year period. PMID- 1887325 TI - [Poisoning by paralytic molluscan toxins in Oaxaca]. AB - Toxic Red Tides are caused by marine dinoflagellates which synthesize neurotoxins that accumulate in bivalve mollusks. Upon ingestion, these shellfish can cause paralysis and death. During the month of December, 1989, 99 cases of Paralytic Shellfish Poisoning in the areas of Salina Cruz and Huatulco, Oaxaca, were reported; three of which died. The majority of the cases involved the ingestion of oysters and clams. A short time later, the Red Tide was reported appearing. One hundred and fifteen seafood samples were analyzed through a biologic test in mice to determine the quantity of saxitoxin. Oysters and clams showed levels reaching 4 000 U.R. Laboratory analysis of seawater found very high quantities of Gimnodinium catenatum and Gonyaulax catenella. The control measures consisted of the prohibition of the harvest and sale of all bivalve mollusks as well as a public warning to avoid the consumption of such shellfish. PMID- 1887326 TI - [Perception of common symptomatology during pregnancy, puerperium and lactation]. AB - The objective of this investigation was to identify women's perception on normal and abnormal symptoms of pregnancy, puerperium and breastfeeding; its purpose was to assess the varying educational needs in the geographical area where a reproductive health education program will be implemented. 405 fertile females living in non-residential areas were interviewed in their homes. A predominantly pre-coded questionnaire was used; items related to reproductive health, preventable and susceptible to education were included. Symptomatology perceived incorrectly as normal: a) In pregnancy: Dysuria: 24 percent, genital hemorrhage: 15 per cent, absence of fetal movement: 23 per cent, did not know how to recognize preterm birth symptoms: 70 per cent. b) In puerperium: Increased quantity in lochia rubra: 17 per cent, fever: 22 per cent, fetid lochia: 28 per cent, and c) In breastfeeding: Breasts red and warm: 48 per cent, fever: 30 per cent, nipple fissures: 70 per cent. Symptomatology perceived incorrectly as abnormal: a) In pregnancy: Frequent urination: 17 per cent, morning nausea in the 1st trimester: 9 per cent, emotional instability: 21 per cent, Braxton Hicks contractions: 41 per cent, and b) Postpartum period: Decreased quantity in lochia rubra: 9 per cent, non-fetid lochia alba: 43 per cent, calostrum: 20 per cent. The assessment educational needs showed an inaccurate identification of abnormal and normal obstetric events; its frequency varied. It is essential that a pregnant woman be well informed and educated in order to preserve her own health as well as that of her unborn child. She must be able to recognize warning signs, take action and demand appropriate medical care. Health care personnel and health educators must be responsible for the promoting of maternal and child health during pregnancy. PMID- 1887327 TI - [Autopsy: reflection of intrahospital mortality]. AB - Autopsies have long been viewed as a biased source of information with regard to the mortality statistics that prevail in the hospital and community. This bias could be of either a demographic or clinical nature. Our objective was to define the autopsy characteristics from the National Cancer Institute of Mexico and determine how representative they were of hospital mortality. Age, sex, place of residence, socioeconomic status, and tumor location were obtained from the Hospital Mortality Registry (1985 and 1987). During these two years, 451 deaths were registered; in 290 of these cases (64.3%), an autopsy was performed. Discrepancies of 9.8 percent were found between autopsy diagnosis and mortality registry data. Our results indicate that autopsy examinations effectively reflect total hospital mortality, and represent a useful tool for epidemiological cancer studies in Mexico. Furthermore, we believe that mortality statistics should be based on autopsy results. PMID- 1887328 TI - [Psychological effects on medical students caused by earthquakes of 1985]. AB - Eight months after the earthquakes of September 1985 in Mexico City, an analysis about the psychological symptoms, commonly associated with traumatic experiences was performed, among a population of 708 students, coursing the first year of Medical School. By means of a questionnaire, they reported the symptoms they had experienced before the earthquakes, during the following two weeks, and at the moment of the survey was still higher symptoms at the moment of the survey was still higher than before the earthquakes, so eight months appear to be an insufficient lapse for the complete remission of new cases. About 15.8 per cent of the studied population reported symptomatology that can be considered as having been triggered by the earthquakes. Another sector of the population (11%), previously symptomatic, reported remission after the earthquakes. The group of students directly affected by severe injuries for deaths of either family members, cohabiting persons, or of persons with whom strong affective ties prevailed, showed a greater tendency to present symptomatic states. Women represented the group most affected psychologically by the earthquakes. PMID- 1887329 TI - [Accidents, violence and traumatic lesions. A new look at the use and conceptual analysis of the terminology]. AB - One of the barriers that has arisen for the prevention of injuries provoked by accidents and violence has been precisely that of the consideration of these terms as a health problem in and of itself; in actuality, they only constitute the mechanisms through which said injuries arise. At the moment, the usefulness of these terms is based on the fact that they offer the possibility of identifying the injury as either inadvertent of deliberate. Likewise, one of the goals of this work is to reflect upon the problems that arise from the inadequate use of these terms, as well as the implications and limitations of their use. This has had an effect on prevention and on the partial approach to the real cause of this health problem which turns out to be traumatic lesions, one of the prime causes of death and illness in infants, young persons, and the middle age in our country. PMID- 1887330 TI - [200 years of digitalis]. PMID- 1887331 TI - Genetic mapping in the mouse of four loci related to the jun family of transcriptional activators. AB - Southern blot analysis of DNAs from somatic cell hybrids and the progeny of an intersubspecies backcross were used to identify and chromosomally map four loci in the mouse containing sequences cross-reactive to members of the jun family of transcriptional activators. The murine homolog of v-jun, Jun, was mapped to chromosome (Chr) 4, and a locus containing jun B-related sequences (Junb) was mapped to Chr 8. Probes for jun D identified two genetic loci; one, Jund-1, is near Junb on Chr 8, and a second, previously unidentified locus termed Jund-2, was mapped to Chr 2. PMID- 1887332 TI - Transduction of the CHO aprt gene into mouse L cells using an adeno-5/APRT recombinant virus. AB - An adenovirus-5 recombinant virus Adapt1 carrying the Chinese hamster ovary (CHO) adenine phosphoribosyltransferase (aprt) gene was constructed by insertion of a 2.5-kb fragment containing the complete CHO aprt structural gene linked to a Moloney murine sarcoma virus (MSV) promoter into the E3 region of adenovirus-5. The CHO aprt gene was in the opposite orientation to the adenovirus E3 promoter. Mouse Lapt- tk- (LAT) cells expressed the CHO aprt gene when infected with the virus, even at low MOI (O.1). APRT activity was detectable from approximately 20 h postinfection. At a low frequency, LAT cells were transformed to aprt+, and four stable transductants were selected in adenine, azaserine (AA) medium. Such cells expressed APRT at approximately 50% wild-type activity and the enzyme was shown to be CHO APRT by starch gel electrophoresis. DNA was isolated from the transductants and probed with CHO aprt-specific DNA and with viral DNA probes. The results indicated that the CHO aprt gene was integrated into the LAT cells at a site other than mouse aprt. Although neighboring viral sequences were integrated and maintained in the transductants, viral sequences further upstream and downstream of the aprt gene were absent. PMID- 1887333 TI - Effect of an adjacent base on detection of a point mutation by restriction enzyme digestion. AB - While routinely mapping point mutations within the arginase locus of a collection of hyperargininemic patients, we discovered that a base immediately outside a restriction endonuclease recognition site (TaqI) can eliminate cleavage of this site by this enzyme. The genetic lesion lay in a base immediately flanking a TaqI recognition site within exon 8 of the arginase locus and abolished cutting by approximately 80%. We wish to emphasize the necessity of heeding subtle cues frequently encountered while generating restriction enzyme data, because neither Southern blot maps nor endonuclease digestion of polymerase chain reaction amplified products of exon 8 accurately predicted where the point mutation lay. To our knowledge, this is the first instance of inhibition of cleavage by flanking bases occurring on natural (nonsynthetic) DNA substrates, i.e., within the clinical setting of characterization of a human genetic disorder. PMID- 1887334 TI - Gene expression and metastasis of somatic cell hybrids between murine fibroblast cell lines of different malignant potential. AB - We have used somatic cell hybrids to study the relationship between ras sensitivity, metastasis, and the expression of ras-responsive or "metastasis associated" genes. We have previously shown that NIH 3T3 cells are nontumorigenic, but are made metastatic by transfection and expression of activated ras (i.e., they are ras-sensitive). LTA cells, however, are initially tumorigenic, but nonmetastatic, and are not altered in malignancy by ras (i.e., they are ras-resistant). We also have shown that patterns of expression of ras responsive and "metastasis-associated" genes differ markedly between these two cell types. In the present work, we have constructed three sets of somatic cell hybrids: NIH 3T3 X LTA cells (designated NL), NIH 3T3 X ras-transfected LTA cells (designated NLR), and LTA X ras-transfected NIH 3T3 cells (designated LNR). In all three sets of cell hybrids, pooled clones were found to be highly metastatic in the chick embryo assay, suggesting complementation had occurred. Those cell hybrids that contained ras (NLR and LNR hybrids) were significantly more metastatic than those that did not (NL hybrids). Selected clones of low and high metastatic ability from both NL and LNR fusions were examined for tumorigenicity and "experimental" metastatic ability in nude mice, as well as for expression of several genes thought to be involved in ras-induced progression and malignancy. Patterns of expression of these genes showed a relationship to level of malignancy of the hybrids and demonstrated a responsiveness to the expression of activated ras. These results suggest that the complementation of phenotype observed in the hybrids may arise through a gene regulatory factor(s) supplied by the NIH 3T3- to the LTA-derived parent. PMID- 1887335 TI - Deficient synthesis of MTHFD, a trifunctional folate-dependent enzyme, in the CHO Ade E mutant. AB - MTHFD is a folate-dependent trifunctional protein comprised of three activities: N5,N10-methylenetetrahydrofolate dehydrogenase, N5,N10-methenyltetrahydrofolate cyclohydrolase, and N10-formyltetrahydrofolate synthetase. The enzymes catalyze sequential interconversion of tetrahydrofolate derivatives required for purine, methionine, and thymidylate synthesis. A Chinese hamster ovary cell line (Ade-E), reported to have reduced cyclohydrolase activity, was studied to characterize the nature of the mutation. Enzymatic assays showed reduced activities of all three enzymes of the polypeptide. Immunoblotting and immunoprecipitation of radiolabeled cell extracts indicated that MTHFD protein was greatly reduced or absent in the mutant. Northern analysis of a clonal derivative of Ade-E revealed normal levels of MTHFD mRNA. These results suggest that the mutation affects a posttranscriptional process in the synthesis of the trifunctional enzyme. PMID- 1887336 TI - Effects of flanking base sequences on 5-bromodeoxyuridine mutagenesis in mammalian cells. AB - The molecular mechanisms of incorporation-dependent, 5-bromodeoxyuridine (BrdU) induced mutagenesis were analyzed in murine A9 cells that possess a single copy of the Escherichia coli gpt gene integrated into the chromosomal DNA as part of a shuttle vector. Four independently derived GPT- mutants with single base changes within the integrated gpt gene were utilized in BrdU-induced reversion analyses to test the relative mutability of guanine residues in four different settings: the 5' and 3' guanine residues of a GG doublet, the 3' guanine residue of a GGGG quartet, and the middle guanine residue of a GGG triplet. Two of the mutant lines possessed GG doublet sequences in which a GC----AT transition at either guanine residue of the doublet leads to restoration of GPT enzyme activity without restoring wild-type DNA sequence. Both lines were shown to be effectively reverted by BrdU incorporation-dependent mutagenesis, and sequencing of the gpt genes from numerous independently derived revertants of both lines demonstrated that greater than 90% of the revertants arose due to GC----AT transitions at the 3' guanine residue of the doublet. BrdU-induced reversion of two additional GPT- mutant lines demonstrated that the 3' guanine residue of a GGGG quartet is efficiently mutated, while the middle guanine residue of a GGG triplet sequence is at least 10-fold less mutable by BrdU incorporation-dependent mutagenesis than the 3' guanine residue of a GG doublet or GGGG quartet. All four mutant lines tested were equally revertible by treatment with the alkylating agent ethyl methane sulfonate. The results from this study define a sequence-specific mechanism for BrdU-induced, incorporation-dependent mutagenesis and demonstrate the use of reversion analysis for the determination of sequence specific effects at precise sites within a gene. PMID- 1887338 TI - Should ACE inhibitors be the drugs of choice in the treatment of hypertension in diabetes mellitus? ACE inhibitors are the drugs of choice in diabetic nephropathy. PMID- 1887337 TI - Expression of a human cDNA encoding a protein containing GAR synthetase, AIR synthetase, and GAR transformylase corrects the defects in mutant Chinese hamster ovary cells lacking these activities. AB - The isolation of a human cDNA encoding the multifunctional protein containing GAR synthetase, AIR synthetase, and GAR transformylase by functional complementation of purine auxotrophy in yeast has been reported. Chinese hamster ovary (CHO) cell mutant purine auxotrophs deficient in GAR synthetase (Ade-C) or AIR synthetase plus GAR transformylase (Ade-G) activities were transfected with this human GART cDNA subcloned into a mammalian expression vector. This restored 49-140% of the activities of GAR synthetase, AIR synthetase, and GAR transformylase in transfected cells when compared to wild-type CHO K1 parental cells. Study of one stably expressing transfectant, AdeC2, revealed that the human GART cDNA was incorporated into the CHO genome. The enzyme activities appear to be associated with an expressed protein of 110 kDa, very similar to that of purified human GART trifunctional enzyme. The Ade-C mutant shows reduced amounts of GART mRNA compared to CHO K1 and a protein of apparently reduced size, results consistent with the purine requirement and enzyme deficiency observed in the mutant. These experiments provide definitive evidence that the human GART cDNA encodes and can direct the production of active human GART trifunctional protein in mammalian cells. They also provide important evidence that the Ade-C and Ade-G mutants of CHO cells are defective in this gene. PMID- 1887339 TI - Are ACE inhibitors cardioprotective? ACE inhibitors prevent post-infarction arrhythmias and reinfarction. PMID- 1887340 TI - Are ACE inhibitors cardioprotective? ACE inhibitors improve cardiac function. PMID- 1887341 TI - Should ACE inhibitors be the drugs of choice in the treatment of hypertension in diabetes mellitus? ACE inhibitors have a more beneficial effect on biochemical parameters than low-dose thiazides. PMID- 1887342 TI - South African health care in change. PMID- 1887343 TI - Poorly nourished children and psychometric measurements. PMID- 1887344 TI - South Africa's unmet health needs--do we need medical auxiliaries? PMID- 1887345 TI - Emergency treatment of Jehovah's Witnesses. PMID- 1887346 TI - Sub-cervical spinal injuries with neural involvement. The Ga-Rankuwa Hospital experience. AB - A retrospective analysis of 48 patients with injuries of the thoracic and lumbar spine and with neural involvement showed that motor vehicle accidents (62.5%) and a fall from a height (20.8%) were the most common causes of injury. T11-L2 was the segment of the spine most commonly affected, accounting for 70% of all vertebral injuries. Associated, non-spinal injuries, frequently severe, were present in 50% of patients. There were 27 complete and 14 incomplete spinal cord injuries; of the cauda equina lesions, 3 were complete and 4 incomplete. Surgical reduction and stabilisation with dual Harrington distraction rodding, supplemented by sublaminar wiring, was performed in 85% of patients. Surgery reduced the period of obligatory bed-rest by half, but shortened the mean time in hospital by only 2.4 weeks (16%). Surgery did not appear to promote neurological recovery and no patient deteriorated neurologically in the course of treatment. Four out of 7 patients treated non-surgically improved neurologically, as did 14 out of 41 who underwent surgery. Ultimately, 17 patients became ambulatory, with or without walking aids. The Harrington rodding system as used was found to be reliable without additional external bracing. Dislodgement of hooks occurred in 7 patients. These all occurred as a result of judgmental or technical error and should be entirely preventable. PMID- 1887347 TI - Recurrent spontaneous abortion--aetiological factors and subsequent reproductive performance in 76 couples. AB - A diagnostic screening programme identified a possible aetiological factor in 32 of 76 couples (42%) evaluated for recurrent spontaneous abortion (three or more consecutive abortions). The abnormalities most commonly observed were endocervical infections (18%), cervical incompetence (11%) and uterine abnormality (9%). Hypothyroidism was present in 3 women and chromosomal abnormality in 2. None were positive for lupus anticoagulant. Treatment of uterine abnormality and cervical incompetence was associated with 75% and 86% success rates, respectively, whereas treatment of infective causes resulted in a 44% successful pregnancy rate, much the same as the 42% rate that occurred in women who had not been thus treated. PMID- 1887348 TI - Direct intracompartmental pressure measurement in the management of snakebites in children. AB - Snakebite remains a source of considerable morbidity in Natal. Despite the availability of specific and polyvalent antivenins, the regional effects of envenomation and inappropriate first-aid result in significant, potentially avoidable, disability--particularly in children. Direct measurement of intracompartmental pressure has been used as an adjunct to clinical assessment of the child with a swollen limb following snakebite in order to diagnose compartment syndrome. Initial encouraging results in 9 patients suggest that, in this difficult clinical situation, such measurements may have an important role in patient assessment. PMID- 1887349 TI - [Sex education of teenagers in Paarl]. AB - Over a 24-month period, 209 pregnant girls 16 years and younger were interviewed at the Paarl East Teenage Pregnancy Clinic. Only 60 (28.71%) had received some sex education at home and 108 (51.67%) had received some information at school. Fifty-seven girls (27.2%) had received no instruction at all. This lack of sex education partly explains the high incidence of teenage pregnancy at Paarl--once reported as the highest in the world. Eradication of this teenage catastrophe afflicting South Africa must involve improved school education and the total community, including the business sector. Teenage instruction should start at junior school and should be repeated at frequent intervals from as early as Standard 2. PMID- 1887350 TI - Tick-bite fever in Zimbabwe. Survey of antibodies to Rickettsia conorii in man and dogs, and of rickettsia-like organisms in dog ticks. AB - As part of a study of tick-bite fever in Zimbabwe, the prevalence of antibodies to Rickettsia conorii in dogs and humans was examined. Blood samples were obtained from 184 dogs in different parts of the country and tested by indirect immunofluorescence. In all, 150 (82%) were positive at a titre of 1/40 or higher. Dogs from the south and east of the country showed very high seroprevalence compared with dogs from the main urban centre, Harare. Human serum was obtained from blood donors, from people attending clinics with non-febrile illness and from agricultural workers. Antibodies to R. conorii were found in a high proportion of samples from the south and east, with 100% of blood donor samples in one area being positive. As with the dogs, a much lower proportion of samples from Harare were positive. The exact role of dogs and their ticks (Rhipicephalus sanguineus, R. simus and Haemaphysalis leachi) in the epidemiology of human tick bite fever remains unclear, since dog ticks were seldom found to harbour rickettsia-like organisms and man is not one of their preferred hosts. While dogs may be of little importance in disease transmission, their value as sentinels of spotted-fever group rickettsias in the environment was confirmed. PMID- 1887351 TI - Intra-ocular concentration-time relationships of subconjunctivally administered gentamicin. AB - Eighty-nine patients scheduled for cataract removal or lens implantation were divided randomly into three groups. Each received 5, 10 or 20 mg gentamicin subconjunctivally at times varying between 0.2 and 19 hours pre-operatively. At surgery a sample of aqueous humour was obtained and analysed for gentamicin concentration. The data for each group were subjected to non-linear regression analysis to fit an open one-compartment pharmacokinetic model with first-order kinetics. A statistically acceptable fit was obtained. The average values of the pharmacokinetic parameters obtained from the single doses were used to simulate multiple-dose kinetics. The average target intra-ocular gentamicin concentrations and dosage interval were specified in the computer program, which subsequently allowed calculation of the dose required. This allowed the construction of a simple linear nomogram that can be used to read off the dose needed for handling specific clinical situations. PMID- 1887352 TI - The theophylline content of bronchodilator preparations on the South African market. AB - The availability of over 40 different theophylline-containing preparations on the South African market poses a therapeutic dilemma when a change in bronchodilator becomes necessary, or when a patient on theophylline therapy self-medicates with an over-the-counter theophylline-containing cough medicine. This occurs because of the lack of uniformity in stating the theophylline content on the label. For example, a change in a patient's prescription from Choledyl 200 mg (200 mg oxtriphylline equivalent to 127.2 mg anhydrous theophylline) to Theodur 200 mg (200 mg anhydrous theophylline) will result in an increase in theophylline dose of over 56%. This potential for toxicity is not apparent because the label indicates the mass of the 'salt' rather than the anhydrous theophylline content. A table of currently available theophylline containing preparations on the South African market is presented. PMID- 1887353 TI - Serological markers of sexually transmitted diseases associated with HIV-1 infection in pregnant black women. AB - While the prevalence of HIV-1 is increased in women attending sexually transmitted diseases (STD) clinics, in South Africa little is known about STD risk factors in women infected with HIV-1 in the general population. Serological markers of STDs were investigated in a cohort of 21 pregnant women, who were found to be carriers of HIV-1, and in 42 age- and residentially matched uninfected pregnant women. The rapid plasma reagin test (RPR) was positive in 33% of the HIV-1- infected women (P less than 0.05 compared with controls). The specific treponemal fluorescent antibody absorbed test (FTA-abs) was positive in 43% of the HIV-1-infected women (P less than 0.05 compared with controls). Similarly the prevalence of chlamydial IgG antibodies as measured by enzyme linked immunosorbent assay was 95% (P = 0.026 compared with controls). Markers of hepatitis B infection were similar to both groups. Pregnant women with HIV-1 infection in the Johannesburg area have an increased seroprevalence of markers of STDs and more data are required on the attitudes and sexual activity of these women in order to target AIDS and education information. PMID- 1887354 TI - A consultation between Andreas Vesalius and Ambroise Pare at the deathbed of Henri II, King of France, 15 July 1559. PMID- 1887355 TI - Centronuclear myopathy--an inherited neuromuscular disorder. A report of 3 cases. AB - Three patients with the adult form of centronuclear myopathy are presented. The slow progression of this disorder is confirmed. The investigations included muscle and sural nerve biopsies. The electron microscopic findings in the muscle of these patients are unique, as are the results of histological examination and histochemical tests. The sural nerve studies were within normal limits. Insulin estimations in response to glucose loading were normal, which largely negates the possibility of an insulin-receptor defect in this disorder. PMID- 1887356 TI - Time of onset of clinical envenomation following snakebite in southern Africa. PMID- 1887357 TI - Emergency treatment of neurotoxic snakebite with a self-inflating manual bag. PMID- 1887358 TI - Effects of a 1% chlorhexidine gel on the cariogenic bacteria in high-risk elders: a pilot study. AB - Root caries in dentate elderly patients is a problem which may be controlled with chlorhexidine. The purpose of this pilot study was to establish the extent and duration of the antimicrobial effects from an intensive regimen of a 1% chlorhexidine gel in institutionalized elders who had experienced high caries activity in the previous year. Stimulated saliva samples from all subjects before treatment produced more than 105 colony forming units/milliliters of Streptococcus mutans (mean: 2.0 x 10(7); s.d.: 2.0 x 10(7)) when diluted and cultured on Mitus Salivarius-bacitracin agar for 48 hours. Findings suggest that daily treatments for 1 week with a 1% chlorhexidine gel can reduce the number of cariogenic bacteria in elderly people for approximately 3 weeks after treatment. PMID- 1887359 TI - Gingival hyperplasia: a side effect of nifedipine and diltiazem. AB - Currently, calcium channel blockers are being used increasingly for the treatment of hypertension in the elderly. Several case reports in the dental literature suggest that patients treated with the calcium channel blockers manifest gingival hyperplasia similar to that seen in patients taking phenytoin (Dilantin, Parke Davis). A small study of 89 patients undertaken at the Westside Veterans Administration Medical Center, Chicago seems to indicate that nifedipine and diltiazem do indeed cause gingival hyperplasia. A total of 83% of the patients studied receiving nifedipine showed evidence of hyperplastic tissue and 74% of those on diltiazem were found to have hyperplastic tissue. PMID- 1887360 TI - The cause and management of burning mouth condition. AB - This paper reviews the clinical presentation and many causes of burning mouth condition. A diagnostic approach and some management procedures that include eliminating all oral irritants, correcting predisposing systemic disease, and most important of all, allaying anxiety that induces parafunctional mouth habits. The term "burning mouth condition" (BMC) is considered more appropriate than the word "syndrome" for this common and troublesome complaint. PMID- 1887361 TI - [The treatment of uterine carcinomas. A report on the cure results at the Hannover Medical College]. AB - From 1971 to 1980, 639 patients with carcinoma of the cervix and 271 patients with endometrial cancer were treated in the Division of Radiation Therapy of the Medical School Hannover. In 606 patients radical radiation therapy was followed by routine surgery, 304 patients have been irradiated primarily due to the local spread of the tumor. The radiation therapy consisted of a combination of external beam and intracavitary therapy. In patients with carcinoma of the cervix the five year survival was 92% for stage Ia, 78% for stage Ib, 67% for stage IIa, 47% for stage IIb, 20% for stage III and 7% for stage IV. In patients with endometrial cancer the five-year survival was 91% for stage I, 71% for stage II, 60% for stage III and 0% for stage IV. Severe complications, i.e., ureteral stricture or fistula occurred in 1% to 1.5% of the patients with cervix cancer and in 0.5% to 1% of the patients with endometrial cancer. PMID- 1887363 TI - [The dosage calculation of very small irregular electron irradiation fields. 2. The dosage distribution at the edge of the field]. AB - Cross beam dose distributions of the small square electron fields (1 x 1 to 6 x 6 cm2), used in the first part of this paper, have been measured at a linac equipped with metal diaphragms attached to a closed cone. They have been used for calculation of the mean square radial displacements sigma 2 of the corresponding pencil beams. Due to complicate electron scattering at the cone and the diaphragm, the pencil beam method could not be used with the simplicity and accuracy desired in practice. Therefore, the therapeutical sufficient field widths, field areas and integral doses have been determined directly from the measured dose distributions, and are represented in dependence from the geometric field size. For small fields we found considerable reductions of these values, which, in practice have to be compensated by enlargement of the geometric field size. PMID- 1887362 TI - [Comparative studies on immunomodulation via hyperfractionated whole-body irradiation]. AB - The effect of the humoral immune response on Sprague-Dawley rats by hyperfractionated total body irradiation was investigated. These experiments included single doses of total body irradiation (1 Gy, 2 Gy, 3 Gy) and the administration of 1 Gy and 2 Gy in two or three fractions 2 x 0.5 Gy, 3 x 0.33 Gy and 2 x 1.0 Gy, 3 x 0.66 Gy. The time between the fractions was six hours. The primary production of antibodies against erythrocytes of sheep were determined as immunity parameter. The immune stimulation could be achieved, when single doses of 1 or 2 Gy were delivered. The single dose of 3 Gy total body irradiation showed a small, not significant immunosuppression. A significant immunosuppression was observed in all our hyperfractionated experiments. The degree of immunosuppression was nearly equivalent in the hyperfractionated group (2 x 0.5, 3 x 0.33 Gy and 2 x 1.0, 3 x 0.66 Gy). PMID- 1887364 TI - [A modified facial mask device for the radiotherapy of head-neck tumors]. AB - The reproducibility during radiotherapy of head and neck tumors has been significantly improved by special devices like individual masks. However, the temporary fixation of head and neck region to the irradiation berth induces in many patients anxiety state and reduces this way the compliance. By means of modification of the device used till now a new model in which the set up mask is only coupled to the berth, could be developed. The clinical evaluation showed that this form of fixation device is much better tolerated by the patients and can be adapted without any problems to all equipment pieces in a radiotherapy department. The estimated reproducibility was comparable to that obtained with mounted device. The average translation of the central beam during 21 days observation period was 2.6 +/- 1.4 mm (0 to 9 mm) in the sagittal plane and 3.4 +/- 1.0 mm (1 to 8 mm) in the frontal plane. PMID- 1887365 TI - [Aluminum, steel and tungsten portal film cassettes for the imaging verification of 60Co photon irradiation up to 42 MV in a clinical trial]. AB - The movement of the patient lowers the contrast of the portals, because the exposition time is long and identical with the treatment time. To enhance the contrast in the portals, the first models of the cassettes were modified under the clinical tests by a rear sheet nearly free from backscattering. With the modified cassettes iodine contrast media are weakly seen on the portals in the laboratory tests, but not in the clinical routine. PMID- 1887366 TI - Biophysical aspects of the integrated combination of cytostatic drugs with radiotherapy. Part 2: Dose-effect relationships and 31P NMR spectroscopy of L 1210 cells (monolayers) and 9L glioma cells (monolayers and tumor spheroids) treated with activated isophosphamide, adriamycin, epirubicin and 6 MeV electrons. AB - Dose-effect relations have been evaluated by the treatment of cell cultures (9L glioma cells of rat as monolayers and tumor spheroids, L 1210 cells of mice) with activated isophosphamide, adriamycin, epirubicin and 6 MeV electrons. The magnitude of synergistic effects obtained by combined treatment modalities is strictly pH-dependent, but even for tumor spheroids it appears that there exists an optimum time-interval between drug administration and consecutive irradiation. The determination of the intracellular pH value with the help of pH sensor microelectrodes and 31P NMR spectroscopy indicates that 31P spectroscopy only provides the global pH of the complete culture (average value), whereas the local pH can only be determined by sensors. The ATP-concentration before and after irradiation depends significantly on the glucose supply of the culture medium. PMID- 1887367 TI - Acid phosphatase response in murine rhabdomyosarcoma for various tumour volumes and after different doses of neutron irradiation, alone or combined with exogenous ATP. AB - Acid phosphatase activity measured in a methylocholanthrene-induced murine rhabdomyosarcoma showed a monotonically increasing relation between enzyme activity and tumour volume. This could be related to the lytic activity of the enzyme in large tumours which become more hypoxic and necrotic, and hence enhance degradation and turnover of damaged tumour cells. The tumours were also subjected to irradiation using doses of 2.0, 3.8 and 6.0 Gy from a neutron therapy facility p(66MeV)/Be. The correlation between different doses and response of acid phosphatase activity could reflect the relation of magnitude of damage from metabolic disturbances, with dose. Furthermore exogenous ATP was shown to provide radioprotective action against neutron irradiation in two different experiments. The ATP reduced the activity of this lytic enzyme in irradiated tumours and also decreased tumour growth delay. This radioprotective role of exogenous ATP in a murine tumour could be related to physiological regulatory processes during defence mechanisms to maintain self-organisation in response to the radiation damage. PMID- 1887369 TI - Sphincter-sparing surgery. AB - Since World War II, a variety of technical innovations have been introduced to preserve the anal sphincter in patients with chronic ulcerative colitis or tumors of the rectum. Studies of anorectal physiology have yielded guidelines for preserving continence and minimizing morbidity. For example, preservation of the anal rectal angle is essential; the rectal mucosa can be removed without impairing neural mechanisms; construction of a reservoir increases rectal compliance. Following these guidelines, surgeons have introduced new techniques and applications benefiting a larger and more varied patient population. Some technical problems remain, however, and patient selection criteria for restorative rectal surgery need to be refined. PMID- 1887368 TI - Radioprotection of whole-body gamma-irradiation-induced alteration in some haematological parameters by cysteine, vitamin E and their combination in rats. AB - Radioprotective effect of cysteine, vitamin E and their combination on gamma irradiation-induced alteration in some haematological parameters in male rats has been studied 24 and 48 hrs after whole-body gamma-irradiation at a dose level of 7.5 Gy. The results of this study reveal that gamma-irradiation caused a significant decrease in red blood cells (RBCs) count with insignificant change in hemoglobin level, 24 and 48 hrs postirradiation, gamma-irradiated rats showed as well a progressive decrease in their blood ATP, and serum-SH levels with a significant increase in blood glutathione (GSH) level. Administration of cysteine or vitamin E preceding gamma-radiation exposure gave a significant radioprotection to the above haematological parameters. However, combination of both agents afforded a better protection, so that most of the measured parameters were restored to the pre-irradiated values. Finally, the date demonstrate that the radioprotection provided by combined administration of vitamin E and cysteine is feasible and perhaps, even more efficient against radiation injury to RBCs. This will appreciate the usage of such combination in protecting the patient during radiotherapy. PMID- 1887370 TI - Approaches to immunotherapy of cancer: characterization of lymphokines as second signals for cytotoxic T-cell generation. AB - Lymphokines, the soluble molecules produced by cells of the immune system, regulate cell-cell interactions and, consequently, the functional status of the immune system. Altering immunoregulatory pathways with lymphokines in vivo may provide a mechanism for controlling a variety of immunologic disorders. Although normally produced in vivo in very small quantities, the widespread availability of recombinant lymphokines has made it possible to study the molecular signals involved in production of lymphocyte effectors with activity against tumor. For example, interleukin-2-based cancer immunotherapy programs have, in certain clinical situations, suggested that immunologic intervention can influence the regression of metastatic cancer. Ultimately the successful application of these biologic agents requires an understanding of the interaction between the immune system and tumor on a molecular level. To induce a given biologic effect, it is necessary both to classify the required lymphokines and to identify the relevant effector cell populations. This review will examine the progress made in identifying the requirements for lymphokine-induced cytotoxic T-lymphocyte function. PMID- 1887371 TI - Analysis of morbidity and mortality rates in right hepatectomy with the preoperative APACHE II score. AB - Morbidity and mortality rates in 70 patients who underwent major liver resection for liver tumors (primary and metastatic) were determined and correlated with the preoperative APACHE II score. Patients were divided into three groups according to their preoperative APACHE II score: low (0 to 3), mid (4 to 7), and high (8 and above). A higher score was closely correlated with increased postoperative morbidity and operative mortality rates. The group with low scores had a postoperative morbidity rate of 34% and a mortality rate of 0%, the group with mid scores had a postoperative morbidity rate of 54% and a mortality rate of 3%, and the group with high scores had a postoperative morbidity rate of 80% and a mortality rate of 20%. Age did not correlate with morbidity. It was therefore postulated that morbidity and mortality rates were related to the combination of points for abnormal physiologic variables and points for chronic health, or APACHE II score minus points for age. As the combination of these points increases the postoperative morbidity and operative mortality rates increase significantly (from 24% in the 0-point group to 69% in the greater than or equal to 3-point group). Also the two deaths occurred in the group with 3 or more points. The preoperative APACHE II score may be used by clinicians to evaluate before surgery the risk of postoperative morbidity and death in elective major liver surgery. PMID- 1887372 TI - Iliofemoral venous thrombectomy followed by percutaneous closure of the temporary arteriovenous fistula. AB - Iliofemoral venous thrombosis treated by anticoagulants alone almost invariably results in postthrombotic sequelae with deep venous reflux alone or combined with an outflow obstruction. This study evaluates the result of iliofemoral venous thrombectomy with temporary proximal arteriovenous fistula (AVF) performed on 48 consecutive patients. In 10 patients the thrombus extended in the inferior vena cava, and the thrombectomy was combined with inferior vena cava interruption. The AVF closed spontaneously in 8 of 48 patients (patency rate, 84%). An attempt to close the AVF by placing a detachable balloon percutaneously under radiographic control was made 6 to 12 weeks later (success rate, 87%; complications, rare). A preclosure arteriovenography of the femoro-iliaco-caval segment revealed 34 of 38 segments open (patency rate, 89%). Four patients had severe stenosis of the iliac segment, and a transvenous percutaneous dilatation was successfully performed in three of the four patients, keeping the fistula. At AVF closure 4 weeks later the arteriovenography showed sustained dilatation in only two patients. Thirty-seven patients were followed for 3 to 48 months (median, 24 months) and 30 of 37 patients (81%) who had no symptoms were not using compression stockings. Doppler investigation revealed patent and competent femoral and popliteal veins and normal photoplethysmography in 56% of the patients. Four iliac veins were occluded (patency rate, 88%). No recurrence of fistula had occurred. Venous iliofemoral thrombectomy seems to better preserve valve function. The percutaneous balloon closure of the AVF has decreased the complication rate, facilitated venographic evaluation of the result, and made possible the performance of percutaneous interventions under the protection of the AVF. PMID- 1887373 TI - Pulmonary and systemic fluid filtration after continuous versus bolus interleukin 2 infusion. AB - Interleukin-2 has been widely investigated as adjuvant therapy for advanced cancer and is administered by either bolus or continuous infusion. We compared the effects of bolus and continuous interleukin-2 infusion on pulmonary (QL) and systemic microvascular fluid filtration in 11 adult sheep prepared with chronic lung and soft-tissue lymph fistulas. Interleukin-2 was administered as a bolus infusion (100,000 units/kg) every 8 hours for 3 days or as a continuous infusion at the same dose for 3 days. No significant changes in pulmonary hydrostatic pressures or pulmonary vascular resistance were noted after either bolus or continuous interleukin-2 infusion. However, significantly decreased (p less than or equal to 0.05) systemic vascular resistances were observed in both groups. QL increased steadily throughout the infusion period in both groups, peaking at three times baseline on the third infusion day. The plasma/interstitial protein clearance (QL X lymph/plasma protein ratio) rose similarly in both groups, indicating increased barrier permeability. Increased lymphocyte clearance into lung lymph occurred by day 3 but was not associated with lymphocytic sequestration in the lung interstitium. We conclude that pulmonary and systemic microvascular fluid and protein flux exhibit similar changes after bolus or continuous interleukin-2 infusion. These changes are associated with increased clearance of lymphocytes into lung lymph that are not sequestered in the pulmonary interstitium after infusions of shorter duration. PMID- 1887374 TI - The hemodynamic response to hemorrhage in tumor-bearing animals. AB - Tumor-bearing rats submitted to hypovolemia have higher mortality rates than have non-tumor-bearing control rats. To determine the mechanisms underlying this sensitivity to hemorrhage, we studied Fischer-344 rats with subcutaneous methylcholanthrene-induced sarcoma (tumor burden, 10% body weight) to determine hematologic and blood volume alterations. Subsequently we used the same animal model in an unanesthetized condition to determine the sensitivity to hemorrhage and resuscitation, as well as vascular responsiveness to vasoactive agents. The rats were separated into two groups: control and tumor-bearing rats (TBR). Sensitivity to hemorrhage and resuscitation was determined by bleeding the conscious rats (15 ml/kg) and resuscitating them with 0.9% NaCl (45 ml/kg). Vascular responsiveness was determined after injection of varying doses of phenylephrine and nitroglycerin, with continuous measurement of mean arterial pressure (MAP). Rate of increase of MAP, maximum MAP, relative increase in MAP (maximum minus baseline), rate of recovery toward baseline MAP, and duration of the response were determined. There was a significant anemia in TBR, but blood volume was similar in both groups. Baseline MAP was significantly higher in control rats (125.3 +/- 8.1 mm Hg) compared with TBR (107.5 +/- 6.0 mm Hg). After hemorrhage, MAP in TBR reached significantly lower levels than in control rats. In addition, after saline resuscitation, MAP in TBR did not return to baseline levels, whereas MAP in control rats returned to prehemorrhage MAP. With nitroglycerin, MAP decreased to lower levels in TBR than in control rats. With phenylephrine, the maximum MAP reached was significantly higher, and the response to phenylephrine was maintained for a significantly longer period in control rats compared with TBR. We conclude that TBR are more sensitive to hypovolemic events in association with decreased oxygen-carrying capacity, profound hypotension, and altered overall vascular responsiveness to sympathetic stimuli. PMID- 1887375 TI - Cerebral hemodynamic effects of fluid resuscitation in the presence of an experimental intracranial mass. AB - We addressed the impact on intracranial pressure (ICP) of posthemorrhage fluid resuscitation with a protocol in which additional fluid was infused to maintain a stable cardiac output after an initial bolus of fluid was infused. Anesthetized, mechanically ventilated mongrel dogs (n = 27) underwent a 30-minute interval of hemorrhagic shock (mean arterial pressure = 55 mm Hg) during which inflation of a subdural balloon maintained ICP at 15 mm Hg. After shock, animals were resuscitated with one of four randomly assigned fluids: (1) slightly hypotonic crystalloid (Na+, 125 mEq.L-1; designated Na-125); (2) hypertonic crystalloid (Na+, 250 mEq.L-1; designated Na-250); (3) slightly hypotonic crystalloid plus 10% pentastarch (Na-125P); or (4) hypertonic crystalloid plus 10% pentastarch (Na 250P). Supplemental fluid was administered as needed to maintain cardiac output comparable to baseline values. ICP increased progressively in all fluid groups during resuscitation. Cerebral blood flow, measured by the cerebral venous outflow method, increased immediately after resuscitation and then declined steadily over time in all groups. Fluids containing pentastarch maintained hemodynamic stability with minimal supplementation throughout most of the postresuscitation period, compared with crystalloid alone, which required substantial additional volume. If decreased intracranial compliance and hemorrhage are combined, ongoing resuscitation is associated with significantly increased ICP and significantly decreased cerebral blood flow, independent of the tonicity and oncotic pressure of the infused fluid. PMID- 1887376 TI - Production of endothelium-dependent relaxation responses by saphenous vein grafts in the canine arterial circulation. AB - To determine if venous endothelium can acquire the ability to elicit endothelium dependent relaxation responses, five dogs underwent femoral artery bypass with autogenous saphenous vein. The veins were harvested 15 to 17 months later. Endothelium-dependent relaxation was determined by measuring tension of deendothelialized coronary arteries mounted on a tensiometer and superfused with the effluent of the vein grafts. These grafts were perfused with acetylcholine and calcium ionophore A23187, which cause case vascular smooth muscle relaxation by means of endothelium-dependent relaxing factor production. Control arteries and veins were obtained from other dogs for comparison. In response to acetylcholine from 10(-9) to 10(-4) mol/L, the final cumulative relaxation produced in the detector coronary artery (mean +/- SD) was 64.2% +/- 25.7% by the control arteries, 14.2% +/- 5.5% by the vein bypass graft, and 5.3% +/- 5.6% by the control veins. In response to A23187 from 10(-8) to 10(-4) mol/L, the final cumulative relaxation was 66.2% +/- 19.0% by the control arteries, 30.6% +/- 8.9% by the vein bypass grafts, and 5.3% +/- 5.6% by the control veins. The differences were significant between the vein bypass grafts and the control arteries (p less than 0.04 for acetylcholine; p less than 0.04 for A23187) and the control veins (p less than 0.03 for acetylcholine; p less than 0.02 for A23187). Perfusion of saphenous veins used as chronic arterial bypass grafts with either acetylcholine or A23187 produced detector vessel relaxation, consistent with endothelium-dependent relaxing factor production. The magnitude of the relaxation response did not approach that from perfusion of control arteries. PMID- 1887377 TI - The detrimental effects of intravenous crystalloid after aortotomy in swine. AB - We tested the hypothesis that, after aortotomy, rapidly replacing three times the blood volume deficit with intravenous crystalloid will increase hemorrhage and decrease survival. Sixteen anesthetized Yorkshire swine underwent splenectomy and stainless steel wire placement in the infrarenal aorta and were instrumented with pulmonary artery and carotid artery catheters. The wire was pulled, producing a 5 mm aortotomy and spontaneous intraperitoneal hemorrhage. The animals had been alternately assigned to either an untreated control group (n = 8) or a treatment group (n = 8), which received 80 ml/kg lactated Ringer's solution intravenously. The volume of hemorrhage and the mortality rate were significantly increased (p less than 0.05) in the treatment group receiving lactated Ringer's solution relative to the control animals (2142 +/- 178 ml versus 783 +/- 85 ml, and eight of eight animals versus zero of eight animals, respectively). From these data we conclude that, in this model of uncontrolled arterial hemorrhage resulting from abdominal aortotomy, rapidly administering lactated Ringer's solution intravenously significantly increases hemorrhage and death. PMID- 1887379 TI - Artificially induced ventricular fibrillation in the management of through-and through penetrating wounds of the aortic arch: a case report. AB - Case report of a 28-year-old woman in whom a through-and-through knife injury of the aortic arch is presented. The hemorrhage could not be brought under control by conventional means and was handled by artificially induced temporary electric fibrillation of the heart, direct suture, and immediate defibrillation. The patient made an uneventful recovery. PMID- 1887378 TI - Role of conversion of xanthine dehydrogenase to oxidase in ischemic rat liver cell injury. AB - This study was undertaken to determine whether hepatic ischemia and the subsequent reflow of blood have any effect on the conversion of xanthine dehydrogenase to xanthine oxidase (XO). Ischemia of the liver for 90 or 120 minutes did not permit survival of the animals. XO represented 15% of the total xanthine dehydrogenase plus XO activity in the control liver. XO activity remained unchanged even after 90 minutes of hepatic ischemia, although a marked increase in lipid peroxide in the liver tissue was observed during the reperfusion. When hepatic ischemia was prolonged for 6 hours (animals were dead), XO activity rose to 35% of the total activity. Incubation of the liver at 37 degrees C resulted in a definite change in XO activity dependent on the length of incubation period. Although no significant changes occurred in XO activity during the first 2 hours of incubation, a marked XO conversion was observed between 2 and 4 hours, and a maximal conversion was achieved after 6 hours of incubation. These results suggest that XO newly generated during ischemia has a very limited role in oxygen free radical production after resuming perfusion. PMID- 1887380 TI - Duodenobronchial fistula. AB - Duodenobronchial fistulas are an extremely rare subgroup of abdominobronchial fistulas, which include bronchobiliary, gastrobronchial, enterobronchial, colobronchial, and splenobronchial fistulas. Only one case of a duodenobronchial fistula has been previously reported. Duodenobronchial fistulas occur as a complication of a duodenal injury. The characteristic symptoms are a cough that produces copious bilious secretions, shortness of breath, and fever. The diagnosis is made by contrast gastrointestinal studies. Treatment requires an abdominal approach with interruption of the fistula at its duodenal origin and control of the inciting inflammatory process. With prompt diagnosis and treatment, thoracic drainage or pulmonary resection should not be needed. PMID- 1887381 TI - Pancreaticobronchial fistula causing lung abscess: case report and brief discussion of the literature. AB - A case report of a patient with an abscess of the lung caused by a pancreaticobronchial fistula is presented. The patient was treated by pulmonary resection and distal pancreatectomy-splenectomy. PMID- 1887382 TI - Ovarian carcinoma metastatic to the breast and axillary node. AB - Breast cancer is a common primary malignancy in women. On rare occasion the breast is also the site of metastatic disease. This report describes the evaluation of breast and axillary masses in a patient with known ovarian cancer, including the radiographic evaluation and special immunohistochemical stains with CA-125. Flow cytometric determinations and hormonal receptor analysis on both the primary and metastatic tumors demonstrate similar biologic characteristics. Both tumor sites demonstrated positive CA-125 staining, aneuploid DNA populations, moderately positive estrogen receptor content, and negative progesterone receptors. The mammogram demonstrated a well-circumscribed lesion with several areas of microcalcifications. Blood-borne metastasis from the ovary to the breast can show a varied clinical picture that can be differentiated from that of a primary breast carcinoma. PMID- 1887383 TI - Placement of an ileal loop urinary diversion back in continuity with the intestinal tract. AB - The use of ileum from a previously constructed urinary conduit for lengthening the small bowel has not been previously reported. We describe a patient with the short-bowel syndrome from previous small-bowel resections, radiation enteritis, and an ileal urinary diversion. The ileal conduit was revised because of recurrent hyperammonemic encephalopathy and apparent stricture of the ureteroenteric anastomosis. In an attempt to increase intestinal length, the ileal conduit was replaced by a colon conduit and the ileum was placed back in continuity with the intestinal tract. The patient had an uneventful recovery, and her chronic diarrhea, nutritional deficiencies, and metabolic derangements resolved. The ileal loop segment regained a normal intestinal appearance on radiographic studies. We suggest that when revision of an ileal urinary diversion is required restoration of the ileum into the intestinal tract may be of particular benefit to patients with the short-bowel syndrome. PMID- 1887384 TI - Chylous ascites and lymphocyst management by peritoneovenous shunt. AB - Although lymphocyst (retroperitoneal lymphocele) is not an uncommon complication after retroperitoneal surgery, with a reported incidence ranging from 0.6% to 48%, the occurrence of chylous ascites is a rare phenomenon. Most reports are anecdotal, and hospital records list the incidence of diagnosis as 0.001% of admissions. Diagnosis of chylous ascites is usually not difficult, inasmuch as aspiration and chemical analysis of the fluid yield the answer. Visualization of retroperitoneal fluid collection by computerized tomography or ultrasonography, however, does always raise the possibility of recurrence of tumor in cases where the primary operation was for cancer. Treatment of smaller lesions can be expectant. Respiratory exercises causing an increase in negative intrathoracic pressure may aid in the movement of fluid through the lymphatics. For larger collections, elemental diets and total parenteral nutrition are also often enough, but surgery is sometimes required. Simple insertion of a peritoneovenous shunt, as in this patient, can be as effective as major operations such as identification and ligation of the offending lymphatic or marsupialization of the cyst. PMID- 1887385 TI - Compartment syndrome complicating prolonged use of the lithotomy position. AB - Two patients with three postoperative calf compartment syndromes, which followed prolonged lithotomy positioning, will be presented. Potential physiologic mechanisms are described, and a review of current cases in literature are summated. PMID- 1887386 TI - Annular colon lipoma: a case report and review of the literature. AB - Colonic lipomas are generally mildly symptomatic or asymptomatic pedunculated or sessile polyps, although they have been reported to cause intussusception or significant bleeding. The difficulty in differentiation is primarily with adenomatous polyps. We describe the unique case of a symptomatic annular colon lipoma simulating an annular colon carcinoma. PMID- 1887387 TI - Uncontrolled resuscitation. PMID- 1887388 TI - Relief of pheochromocytoma headache by immersion of feet in ice water. PMID- 1887390 TI - [The effect of drugs that correct regional blood circulation on the function of the parotid salivary glands in the combined treatment of patients with Sjogren's disease]. AB - A study was made of the effect of some drugs that correct microcirculatory disorders (dimethylsulfoxide (DMSO), heparin, novocaine) on the function of the auricular salivary glands (ASG) in combined treatment of 20 patients suffering from Sjogren's disease (SD). It has been established that the use of the indicated remedies is conducive to a more rapid counteracting of the inflammatory process in the ASG, making it possible to stabilize their function for a long time in persons with the initial and marked stages of chronic parotitis (CP) but not preventing repeated exacerbations of CP. In order to maintain the therapeutic level of the response of the vascular bed of the ASG to DMSO, it is desirable that compresses with DMSO in a "pure" form be applied in 6 hours, using a 1% hydrocortisone ointment "laying" 1 to 2 times a day. PMID- 1887389 TI - [The critical value of residual kidney function in patients with chronic kidney failure from the viewpoint of the concentration of urea and potassium in the plasma]. AB - Residual kidney function was examined in 10 patients with chronic renal insufficiency under balance conditions and in 30 outpatients on the basis of urea clearance (Curea) and potassium clearance (CK). Protein intake was 35-40 g/day (0.5 g/kg/day) and potassium intake was 30-40 mmol/day. Under these conditions the critical values of residual kidney function were as follows: 1) plasma urea concentration (Purea) did not exceed 30 mmol/l if Curea did not drop below 3.8 ml/min; 2) plasma potassium concentration (PK) did not exceed 5 mmol/l if CK did not decrease below 4.1 ml/min. Clinical examination of Curea and CK provides additional information to the examination of creatinine clearance (Ccr) or its plasma concentration (Pcr). Our results suggest that the critical value of residual kidney function cannot be defined only on the basis of examination of Ccr or Pcr. Examination of Curea and CK can help in the interpretation of very high Purea and hyperkalemia in patients with chronic renal insufficiency. PMID- 1887391 TI - [The clinico-psychological correlations and work adaptation of rheumatism patients operated on for heart defects]. AB - Altogether 345 patients with rheumatic fever operated on for heart disease were examined for clinicopsychological correlations and their importance for patients' adaptation to work. Cardiovascular function was estimated with the aid of clinical and instrumental methods (ECG, echocardiography, bicycle ergometry). The psychological personality traits were examined by Quetelet's 16-factorial questionnaire, the type of the attitude towards disease by a personality questionnaire developed by the V. M. Bechterew's Leningrad Research Psychoneurological Institute, work purpose by a specially made up questionnaire. Correlations between the level of adaptation to work and the sociopsychological and clinical signs were studied. The psychological characteristics, work purpose of the personality were found to be of paramount importance for restoration of work fitness, which is of significance in the design of labour prognosis of patients and in expert medical evaluation of the working capacity. PMID- 1887393 TI - [The basic principles of the therapy of reactive arthritis]. PMID- 1887392 TI - [The achievements and outlook in the study of the problem of reactive arthritis in children]. AB - The paper is concerned with certain aspects of the problem of reactive arthritis (ReA) in children and with the data obtained by the author. The emphasis is laid on ReA related to intestinal and nasopharyngeal infections and viewed as an independent disease entity. Some controversial issues are discussed and approaches to further studies into such a complex problem are outlined. PMID- 1887394 TI - [The immunomodulating therapy of rheumatoid arthritis]. PMID- 1887395 TI - [The principles of rheumatological orthopedics of the joints of the upper extremity in patients with rheumatoid arthritis]. PMID- 1887396 TI - [The current problems in the etiology and pathogenesis of Reiter's disease (syndrome)]. PMID- 1887397 TI - [The use of thymus preparations in treating patients with rheumatic diseases]. PMID- 1887398 TI - [Rheumatological syndromes in nonspecific ulcerative colitis and Crohn's disease]. PMID- 1887399 TI - [The inverted form of Buschke's scleroderma]. PMID- 1887400 TI - [Practical games in the teaching of emergency care problems in a department of polyclinical therapy]. PMID- 1887401 TI - [The current system of training family physicians in Canada]. PMID- 1887402 TI - [The clinical and etiological characteristics of reactive arthritis in young people]. PMID- 1887404 TI - [The synovial fluid in reactive arthritis in children]. PMID- 1887403 TI - [The results of the dynamic observation of patients with reactive Yersinia arthritis]. AB - As many as 50 patients with reactive Yersinia arthritis were followed up. There were 4 men and 46 women. The mean age of the patients was 31.1 yr. The mean follow-up period was 30.8 months. In 72% of the cases, the disease was preceded by diarrhea. During the first examination, mono-oligoarthritis was detected in 78% of the patients. Extra-articular alterations (damage of muscles, ligaments, heart, skin changes, etc) were also recorded. The results of bacteriological analyses were positive in 22 out of the 50 patients. In 16 persons, Yersinia might be cultivated from the different biological media: blood, feces, urine, fauces, and synovial fluid. In 47 persons, arthritis took a chronic course. Persistence of antibodies of the types 03 and 09 seen for many years merits attention. Monoclonal anti-Yersinia antibodies were also detectable repeatedly. In 8 patients, in whom Yersinia were cultivated from a lot of the biological media, the disease ran an especially grave course. The role of circulating specific antibodies in patients with Yersinia arthritis and the trigger role they may play in the development of RA and ankylosing spondylarthritis requires further discussion. PMID- 1887405 TI - [The clinical and immunogenetic characteristics of reactive arthritis in children]. AB - Altogether 52 children suffering from reactive arthritis were placed under observation. In 45 patients arthritis developed after nasopharyngeal infection and was marked by a favourable course with a rapid positive dynamics. 7 children with a history of intestinal infection manifested Reiter's syndrome; in these children arthritis was characterized by a grave and prolonged course and by a high laboratory activity. HLA A10 (RR = 2.7), B27 (RR = 2.5) and DR2 (RR = 2.19) antigen were detected significantly more frequently in ReA patients who suffered nasopharyngeal infection. In children with Reiter's syndrome, the genetic markers of predisposition to the disease were HLA A10 (RR = 5.93) and B27 (RR = 149.1) antigens. PMID- 1887406 TI - [Humoral and cellular immune reactions in patients with reactive arthritis]. PMID- 1887407 TI - [The rheumatic complications of pseudotuberculosis in a newly arrived population in Siberia]. PMID- 1887408 TI - [The comparative effectiveness of serological and microbiological studies in the etiological diagnosis of reactive arthritis]. AB - The information content of serological and microbiological studies was studied and compared in 72 patients suffering from enterogenous reactive arthritis. A high level of antibodies to intestinal Yersinia was detected in 11.1% of the patients, positive coproculture in 8.3%. Only one patient demonstrated at a time a high level of antibodies and isolation of intestinal Yersinia coproculture. The causative agent could usually be isolated in patients with the symptoms of enterocolitis. It is assumed that among patients suffering from reactive arthritis there are at least two different groups: with positive coproculture and a low level of antibodies and with a high level of antibodies and negative coproculture. The indicated conditions can be regarded as different phases of the disease in the same patients and reflect the pathogenetic heterogeneity of the patients' group with reactive arthritis. Serological and microbiological tests are viewed as equivalent in etiological diagnosis of reactive arthritis. Emphasis is laid on the fact that microbiological tests are more successful in patients with the symptoms of concomitant enterocolitis. PMID- 1887409 TI - [The status and prospects for the improvement of the rheumatology service]. PMID- 1887410 TI - [Pathology of the gastrointestinal tract in patients with reactive arthritis and its possible role in the pathogenesis of the disease]. PMID- 1887412 TI - [Reiter's syndrome: the clinico-histomorphological correlations]. AB - A total of 11 patients with Reiter's syndrome underwent puncture biopsy of the synovial membrane of the knee joint. At the early stage of the disease the patients showed hyperemia, edema, infiltration with neutrophilic leukocytes, lymphocytes and plasmacytes. At the later stage diffuse and focal infiltrates of lymphocytes and plasmacytes and a rise of the fibrocyte count were predominant. A correlation was established between the degree of edema and pain and histomorphologically ascertained hyperemia and edema of the synovial membrane. As the disease progresses, clinically dominant is the induration of the articular bursa, which correlates with the grade of infiltrative and fibrous alterations established on histomorphology. PMID- 1887411 TI - [The efficacy of bifidum-containing preparations in enterogenous reactive arthritis]. AB - Analysis is made of the intestinal microflora in 43 patients suffering from reactive arthritides (ReA) that developed after intestinal infection. The overwhelming majority of the patients manifested a decrease of the level of the bifidoflora. The disorders of the intestinal microflora were related to the disease activity and standing. Bifidumbacterine was found to produce a significant beneficial effect on the course of ReA and to cause no serious side effects. According to the preliminary data, the efficacy of bifidumbacterin exceeded that of the known basic drug salazopyridazine, thus making it possible to apply the bifidum-containing drugs as basic agents in the treatment of ReA. PMID- 1887413 TI - [The evolution of the articular lesion in Reiter's syndrome]. AB - Evolution of polyarthritis was elucidated in 115 patients with Reiter's syndrome. There were 67% of men and 33% of women. The mean age of the patients was 33 years. 57% of the patients were HLA B27 carriers. In 70% of the patients, arthritis ran an acute course, in 12%, a subacute course, and 18% developed chronic arthritis. The axial skeleton was involved in 1/3 of the test subjects, enteropathies of different localization were detected in 58% of the cases. The author failed to establish criteria for predicting arthritis chronicity. PMID- 1887414 TI - [Blood serum and synovial fluid proteins in Reiter's syndrome]. AB - Individual proteins (transferrin, ceruloplasmin, alpha 2-macroglobulin, IgG, IgA and IgM) were examined in blood and synovial fluid of 11 patients with Reiter's syndrome. ARA-1981 was used as a diagnostic criteria. The control group included 40 patients with rheumatoid arthritis and 31 with osteoarthrosis of the knee joint. Statistically significant differences between the concentrations of individual proteins in patients with Reiter's syndrome, rheumatoid arthritis and osteoarthritis were only established in synovial fluid for IgM and for IgM index Csf/CS. PMID- 1887415 TI - [Coxitis in Reiter's disease: the problems of diagnosis and differential diagnosis]. AB - Based on analysis of the data on 124 patients with significant diagnosis of Reiter's disease, coxitis was discovered in 38 (30.8%) of them. During examination, the early clinical signs were revealed to diagnose any coxitis as were differential diagnostic signs to delineate lesions of the hip joints in seronegative arthritis and/or spondylarthritis (Reiter's disease, ankylosing spondylarthritis and psoriatic arthritis), having an analogous clinico roentgenologic appearance. PMID- 1887416 TI - [The clinico-echocardiographic characteristics of heart involvement in seronegative spondylarthritis (Reiter's disease, Bechterew's disease and psoriatic arthritis)]. AB - As many as 136 patients (76 with Bechterew's disease, 40 with Reiter's disease and 20 with psoriatic arthritic) and 35 practically healthy persons were examined by echocardiography combined with electro-, phonocardiographic and by clinical, x ray and laboratory methods. 62 patients were examined over time (within a period from 1 to 4 years). Echocardiography was used to study in detail the central and intracardiac hemodynamics, the status of the valvular apparatus of the heart and of the aorta. The different clinical characteristics of the disease were established to make a concrete contribution to the development of cardial pathology. The disease duration is the most significant characteristics. A long term prospective follow-up coupled with echocardiographic examinations made over time enabled one to specify the structure of heart damage in patients suffering from Bechterew's disease, Reiter's disease and psoriatic arthritis depending on the hypothetic nature of the damage. PMID- 1887417 TI - [Acute rheumatic polyarthritis in young men]. AB - As many as 200 patients with acute rheumatic fever were examined. Impairment of the joints in the form of classic migrating polyarthritic was detected in 96% of the cases. The knee (in 80%), talocrural (in 72%), slightly rare radiocarpal (in 21%), and elbow joints were mostly damaged. In addition to the above-indicated damage to the joints, one could see slightly atypical injuries in the form of monoarthritis (in 4%), arthritis of small articulations of the feet and hands (in 6%), and of the sternoclavicular articulations (in 3.5%). According to the cytological, biochemical and immunological findings, synovial fluid obtained from 11 patients suffering from acute rheumatic fever did not differ, significantly from synovial fluid of patients with reactive arthritis. PMID- 1887419 TI - [Reactive arthritis in liver diseases]. AB - Arthralgia and arthritis may be one of the early signs of hepatic diseases. Comparison of the course of the articular syndrome with the biochemical and immunological data (cationic proteins, NAD, NADP, antigenic markers of viral hepatitis, T lymphocyte subpopulations, and so forth) allowed one to establish a relationship between the parameters studied, to define an important role they play in early diagnosis of liver injuries, in predicting the course of the autoimmune process in active hepatitis. Extracorporeal methods of treatment for chronic hepatic diseases are an important prophylactic and therapeutic factor in the correction of pathogenetic alterations underlying the diseases. PMID- 1887418 TI - [The diagnostic significance of the surface B-cell marker carrier state in arthritis and other manifestations of rheumatic fever]. AB - To assess the diagnostic importance of B-cellular marker demonstration with the aid of D8/17 monoclonal antibodies in arthritis and other manifestations of rheumatic fever, 175 persons were examined. Of these, 117 patients presented with rheumatic fever and rheumatic heart disease. The marker was identified in 88.9% of the patients and in 10% of the healthy subjects entering the control group. The rate of the marker demonstration did not depend on the clinical manifestations of rheumatic fever (arthritis, carditis, chorea), the disease phase, the disease standing or the intensity of heart damage. It is concluded that marker demonstration in rheumatic fever is of paramount diagnostic value, particularly in little manifest processes. PMID- 1887420 TI - [Reactive arthropathies in malignant hemoblastoses]. PMID- 1887421 TI - [Osteoarthropathy in beta-thalassemia]. AB - A total of 45 patients with beta-thalassemia and 30 patients with thalassemia intermedia underwent clinical and x-ray examinations. Electron microscopy was used to examine biopsy specimens of the synovial membrane from 6 patients with homozygous thalassemia intermedia. It has been revealed that damage to the osseous system and joints is of systemic nature and depends on the clinical form of the pathological process. Morphological methods have demonstrated abnormal metabolism of iron with its deposition in the tissues and impairment of the vessels of the microcirculatory bed. PMID- 1887422 TI - [The HLA system of patients with psoriatic arthritis]. AB - Sixty patients with psoriatic arthritis were examined for the rate of demonstration of A, B and DR loci of the HLA system. As compared to the control group, the patients manifested an increase of the rate of demonstration of A24, B27 antigens as well as of DR4 and DR7, which may serve an adjuvant criterion for the disease diagnosis. The highest rate of B27 antigen demonstration was seen in patients with spondylitis. PMID- 1887423 TI - [The peripheral joint syndrome in ankylosing spondylitis--one of the variants of reactive arthritis]. AB - In 75 patients with central (n = 37) and peripheral (n = 38) ankylosing spondylarthritis, EIA was used to detect serum antibodies to Klebsiella (IgG and IgA) and to the common enterobacterial antigen (CEBA) as compared to the level of the ESR, C-reactive protein and circulating immune complexes. Out of the 75 patients, 53 were examined for the intestinal microflora. Serum antibodies to Klebsiella were demonstrated more frequently in the peripheral form than in the central one, particularly in demonstrating Klebsiella coproculture. The presence of serum antibodies correlated with the disease activity. In the central form, enterobacteria without Klebsiella prevailed in the intestine. In both forms, antibodies to CEBA were demonstrated not so frequently (in 1/4 of the patients). In both forms, a large number of cases (74-80%) showed intestinal dysbacteriosis; in the peripheral form, however, it reached a greater degree. As to the central form, the etiological role of Klebsiella is not absolutely clear. It is more remarkable in the peripheral articular syndrome (reactive arthritis towards Klebsiella?) associated with ankylosing spondylarthritis. PMID- 1887424 TI - [Immune disorders and sensitization to microbial antigens in seronegative spondylitis]. AB - A study was made of immunity in seronegative spondylarthritis. In ankylosing spondylarthritis, reactive arthritides and psoriatic arthritis, the decrease of T cells, T helpers and T suppressors was identified. Patients with ankylosing spondylarthritis and reactive arthritides manifested an increase of the B lymphocyte count. Patients with ankylosing spondylarthritis were demonstrated to be sensitive to Klebsiella (52%), those with reactive arthritides to intestinal yersinia (44%). The phenotype of antigen-binding cells was examined. Of these, 39% appeared to be T lymphocytes, 29% B lymphocytes. The presence of Fc receptors in an appreciable portion of those cells suggests their functional maturity. The inhibition test demonstrated the participation of HLA-B27 in reception of Klebsiella antigens in ankylosing spondylarthritis. PMID- 1887426 TI - [Microcirculatory disorders in patients with psoriatic arthritis]. AB - As many as 39 patients with psoriatic arthritis were examined for hemorheology. Of these, 20 were examined at a time for the status of the microcirculatory bed in the skin and skeletal muscle by 133Xe clearance from the interstitial depot and by laser-Doppler flowmetry at the areas of the clinically intact skin. In 10 patients, the plasma blood viscosity was measured. All the test subjects manifested the clinical signs of damage to the vessels of the microcirculatory bed, namely capillaritis of the palmar surface of the hands and/or of the plantar surface of the feet, sensitivity to cold, numbness of the finger tips. A detailed analysis of the individual aggregation characteristics allowed two groups of patients to be revealed: with a decrease and enhancement of aggregation at a shift rate of 2.5 s-1. It should be noted that patients with severe hemorheological disorders showed both changes on the part of the microcirculatory bed (clinical and quantitative) and a rise of the blood plasma viscosity and hematocrit fall. The data obtained indicate that the microcirculatory and related rheological disorders may be implicated in the pathogenesis of psoriatic arthritis. PMID- 1887425 TI - [Cryoglobulinemia and fibronectin in systemic lupus erythematosus]. AB - EIA was used to measure the concentration of fibronectin in plasma and cryoprecipitates of 37 patients suffering from systemic lupus erythematosus coupled with cryoglobulinemia. A definite relationship was discovered between the level of cryoglobulins and the activity of SLE, the concentration of fibronectin in plasma and liver damage. A tendency was revealed towards increase of the fibronectin content in plasma of patients with a high level of antibodies to native DNA and CIC as was a significant correlation between the concentration of cryoglobulin protein and the concentration of fibronectin in cryoprecipitates. PMID- 1887427 TI - [Reactive arthritis. The problems of theory and practice]. PMID- 1887428 TI - [The function of the effector cells of inflammation in rheumatoid arthritis]. AB - As many as 105 patients with rheumatoid arthritis were examined for function of tissue and circulating neutrophils. The effect of serum factors on the nature of inflammation and synovial fluid was estimated both in the joint and in the focus of aseptic inflammation. The defense mechanisms of regulating inflammation, different trends in the effects of serum and synovial fluid on cell migration and oxygen metabolism were revealed, relations between the phenomena under study and the disease activity and local inflammation were defined. PMID- 1887429 TI - [Prostaglandins in the blood serum of patients with rheumatoid arthritis]. AB - Radioimmunoassay was used to study the content of prostaglandins in blood plasma of patients suffering from rheumatoid arthritis (PGE in 133 and PGF2 alpha in 102 patients). It has been established that as compared to the control group subjects, it is appreciably elevated and reflects the degree of inflammatory process activity, being pronounced to a greater measure in persons not receiving glucocorticoids than in hormone-dependent patients. A relationship has been revealed between the content of PGE and PGF2 alpha and certain clinical and laboratory characteristics (disease standing, intensity of exudative component of inflammation, the presence of humoral and cellular immunity disorders, anemia, and some visceral lesions), which may be of definite importance in the assessment of the patient's status. The time-course of changes in blood plasma prostaglandins reflects on the whole the dynamics of the disease activity, being related to a greater degree to the application of nonsteroidal antiinflammatory agents than of glucocorticoids. PMID- 1887430 TI - [The effect of plasmapheresis on the function of the calcium-regulating systems in patients with rheumatoid arthritis]. AB - As many as 87 patients with rheumatoid arthritis were examined for changes in the status of the calcium-regulating systems under the influence of therapy. The multimodality treatment of 57 of the patients included discrete plasmapheresis, which allowed the attainment of an earlier and more marked beneficial clinicolaboratory effect. Plasmapheresis contributed to the correction of the status of the calcium-regulating systems: to a decrease of the level of parathyrin, an increase of the concentration of calcitonin, calcidiol, total and ionized calcium. PMID- 1887431 TI - [The potentials of colchicine in the combined therapy of secondary amyloidosis in patients with rheumatoid arthritis]. AB - The authors relate the results of prolonged treatment (up to 3.5 years) with colchicin of 22 patients suffering from rheumatoid arthritis (RA) complicated by morphologically verified secondary amyloidosis of the kidneys and/or of the gingival, rectal and hepatic mucosae. Colchicin prescribed as the only slowly acting agent turned out effective in 5 out of 11 patients and in all the 11 patients given the drug in combination with basic therapy by cytostatics or, rarely, by gold drugs and D-penicillamine. The treatment efficacy could be observed both in respect to the manifestations of rheumatoid disease proper and in respect to the manifestations of amyloidosis. The drug did not produce any side effects and could be administered for a long time. In the overwhelming majority of cases, the withdrawal of colchicin, even in basic therapy continuation caused the enhancement of the manifestations of RA and amyloid nephropathy. PMID- 1887432 TI - Organelle rearrangement and cell volume changes during squeezing invasion of peritoneal elastic lamina by targeted murine breast carcinoma cells. AB - Murine breast cancer cell lines were developed to selectively invade the peritoneum while they proliferated in ascites form in the abdominal cavity. In a dominant form of invasion, tumor cells showed special affinity for elastin fibers and squeezed through narrow gaps in the elastic fiber meshwork of the stroma. Even in fixed tissue, such cells could be recognized as being in the process of invasive migration because of their dumbbell shape. This appearance was similar to that of diapedetic blood cells traversing bone marrow sinus endothelium. Three dimensional STERECON graphics reconstruction from serial thick sections of 44 such cells was carried out. The reconstructions showed that, in mid-penetration, the cells spread extensively over the exterior surface of the elastic fiber meshwork. The cell surface contact of these forward projections was mainly with the elastic fiber outer coat of microfibrils, but small areas of the cell surface also fused directly to inner-core elastin. The morphological rearrangement of the cytoskeleton was minimal in both types of attachment areas. The location of these forward facing attachments is consistent with mechanisms for pulling the invasive cell through the gap. Lamellopodia formation and clustering of cytoplasmic organelles occurred more commonly at the forward-facing part of the cell. Morphometry of the reconstructions showed that a contraction of the whole cell occurred during the squeezing/migration process suggestive of an additional pushing process. However, our invasive cell lines showed marked differences in the degree of cell shrinkage. The process of adhesion and squeezing of tumor cells through elastin meshworks in vivo is clearly a complex phenomenon. Changes in cell surface activity appear to play a significant role in establishing the necessary 'foothold' component of invasion and, possibly, in the generation of tractive force as well. PMID- 1887433 TI - Dermal breaks: migratory cell pathways opened in anuran tadpole skin at climactic metamorphosis. AB - In this report, we studied the formation of breaks in the frog dermis during its remodelling at climactic metamorphosis. This remodelling consisted of detachment of the basement lamella collagen from the epidermis. The detached part, called derived collagen, was progressively fractured by breaks. We focused our attention on dermal cell localization during break formation. Firstly, at early climax, dermal cells were localized inside fractures opened in the derived collagen. Secondly, at the later climax, the fractures became breaks, making room for the dermal cells themselves. Thirdly, in derived collagen of the froglet, the well opened breaks contained elongated dermal cells. At climax, DAB immunoperoxidase staining of fibronectin revealed a granular pattern at the surface of epidermal and dermal cells. Unexpected staining revealed that the dermal breaks contained fibronectin in the form of vertical lines. The foregoing results suggest that the dermal breaks are migratory pathways for dermal cells in derived collagen remodelled at climax. PMID- 1887434 TI - Immunofluorescent localization of dopamine-like and leucine-enkephalin-like neurons in the supraoesophageal ganglia of the American cockroach, Periplaneta americana. AB - Leucine-enkephalin- and dopamine-like nerve cells and fibers were localized in the supraoesophageal ganglia (brain) of the American cockroach, Periplaneta americana, using immunofluorescence. The presence of leucine-enkephalin-like material was confirmed using immunoperoxidase staining. Several cells containing leucine-enkephalin-like material were found in the pars lateralis, and nerve fibers belonging to these cells were traced through the brain. Dopamine-like material was detected in deutocerebral neurons as well as the nerve processes arising from these cells which lead into the area of the deutocerebral glomeruli. Specific immunofluorescence was also obtained in the alpha and beta lobes of the corpora pedunculata with both the leucine-enkephalin and dopamine antibodies. However, the fluorescent banding pattern observed in both lobes was distinctly different with the two antibodies. No specific fluorescence was observed in the stalk or peduncle of the corpora pedunculata with either the leucine-enkephalin or the dopamine antibody. The findings suggest a possible interaction of leucine enkephalinergic and dopaminergic nerve fibers in the alpha and beta lobes of the cockroach corpora pedunculata. PMID- 1887435 TI - Fine structure of the dorsal lingual epithelium of the frog, Rana rugosa. AB - Scanning and transmission electron microscopy was employed to investigate the ultrastructure of the lingual dorsal epithelial cells of the frog, Rana rugosa. The specimens for scanning electron microscopy were prepared by a method that involved osmium postfixation and treatment with acid to remove extracellular material that adhered to the surface of the tongue. Over almost the entire dorsal surface, filiform papillae, consisting of a large number of non-ciliated cells with microridges and a very small number of ciliated cells, were compactly distributed. Fungiform papillae were scattered among these filiform papillae. A round sensory disk was located on the top of each fungiform papilla. Each sensory disk was encircled by a band of ciliated cells. Transmission electron microscopy revealed that a large part of the filiform papillar epithelium was composed of cells that contained numerous electron-dense granules. These cells were coincident with the non-ciliated cells observed by scanning electron microscopy. In these cells, the nucleus was located on the basal side, and the ergastoplasm was well-developed on the basal side of the nucleus. PMID- 1887436 TI - [Recent perceptions on the development, assembly and function of the immune system]. AB - The immune system developed through many stages during evolution. It is fascinating that none of the diverse defense mechanisms vanished in such a long period of nearly 3.5 billion years. They still function in the integrated immune system. The barrier system can be compared to the immune system. The immune system itself is subdivided in antigen-independent, paraspecific (primitive immune system) and antigen specific (specific immune system), restricted immune reactions. The role and use of the phylogenetically older, paraspecific mechanisms, that will react immediately after antigen exposure, are discussed in detail. The immune system is not autonomous. It is closely linked to the hormonal, circulatory, metabolic and nervous systems. Its function is comparable to a sensory organ. Psychoneuroimmunology as a new discipline is mentioned. Immunity and paramunity are not seen as opposing phenomena but are linked in their functions. The terminology of immunology is discussed. PMID- 1887437 TI - [Identification of cells of the central nervous system using cell-specific markers]. AB - Cell markers are membrane-associated components of the cellular wall or intracellular substances which are specific for the cell types of any tissue. Markers of the major cell types of the central nervous system (CNS) essentially are the components of the cytoskeleton (microtubules, intermediate filaments), several intracytoplasmic enzymes, and specific components of myelin (myelin proteins, myelin-associated glycoproteins, lipids). In this review the fundamental characteristics of specific CNS markers (astroglia, oligodendroglia, neurons) are discussed and examples of marker application in human and veterinary medical neurosciences are presented. PMID- 1887438 TI - [Immunohistochemical detection of rabies virus antigen in the cardiac ganglia of dogs in paraffin sections]. AB - The hearts of five naturally infected rabid dogs were studied by immunohistochemistry on paraffin sections using a monoclonal antibody and the peroxidase labelled streptavidin-biotin method to detect rabies ribonucleoprotein. In all cases distinct small granular and ring-shaped antigen deposits were found within the nerve cells of the cardiac ganglia thus reflecting the early centrifugal spread of virus along the pathway of the vagal nerve to the heart. Histologic findings consisted only of single small eosinophilic inclusions in some nerve cell bodies. These findings may be of diagnostic value. PMID- 1887439 TI - [The clinical case. Persian cat, male, 4 months old]. PMID- 1887440 TI - [Enzootic otitis in a herd of calves]. AB - Following an outbreak of enzootic bronchopneumonia, 15 out of 19 calves of one herd were affected by uni- or bilateral otitis media. The animals (aged four days to nine weeks) were housed in individual boxes. Type and distribution of concurrent diseases as well as the symptoms indicative of otitis are listed in two tables; two other tables give the results of the bacteriological examinations of aural and nasal swabs taken before and during treatment. In order to cure otitis media, systemic as well as simultaneous local treatments are necessary. The application of oily suspensions of antibiotics into the auditory canal cannot be recommended. Twelve of the 15 sick calves recovered. PMID- 1887441 TI - [Spongiform encephalopathy in a red-necked ostrich (Struthio camelus)]. AB - The paper describes anamnestic, macroscopic and microscopic findings in a female ostrich (Struthio camelus), euthanatized because of central nervous and locomotion disorders. Systemic arteriosclerotic lesions were combined with adiposis and signs of spongiform encephalopathy, localized in the brain stem and the medulla oblongata. Aetiopathogenesis of the disease remains unknown. Differential diagnosis is discussed and the disease compared to similar findings in mammals which suffered from BSE/scrapie. PMID- 1887442 TI - [Pilot study of the relationship of free amino acids in serum and in the cerebrospinal fluid of horses]. AB - In a blind study serum and cerebrospinal fluid (CSF) of control horses and of horses in hepatic coma after chronic food intoxication with Senecio alpinus were collected simultaneously and the composition of free amino acids was determined. The hepatic encephalopathy index in serum (less than 1.65) and in CSF (less than 1.11) of liver patients was distinctly less than to the control values in serum (greater than 2.42) and in CSF (greater than 1.49). The serum concentrations of glutamic acid in hepatic coma were elevated five-fold in comparison to the controls. An indication of ammonia decontamination was that nearly ten-fold higher values of glutamine were found in the cerebrospinal fluids of patients than in serum. In comparison to controls the serum levels of glutamine in horses with hepatic encephalopathy were decreased by the factor 0.7. PMID- 1887443 TI - [Pathomorphology of feline dysautonomia (Key-Gaskell syndrome). Histologic, electron microscopic and immunohistologic findings in 4 cats]. AB - The histopathologic, immunohistochemical and electronmicroscopic findings of four dysautonomic cats are presented. The main histopathologic changes were seen in the nervous system, e.g. in sympathetic and parasympathetic ganglia that were similarly affected. Acute cases showed a degeneration of most of the neurons, in one subacute case less neurons and degeneration of some of the remaining neurons were present. Degenerating neurons were swollen or shrunken and had pycnotic, eccentric nuclei. The Nissl substance was lost, the cytoplasma stained eosinophilic and was often vacuolated. Degenerating neurons were also seen in some nuclei of cranial nerves. In sympathetic ganglia numbers of glial cells were increased as shown by immunohistochemical markers (GFAP, S-100). The main ultrastructural changes in sympathetic ganglia were eccentric, crenated nuclei, loss of Nissl substance, loss of ribosomes, distended cisternae and vacuoles filled with floccular material. Circular stacks of parallel smooth-membranes and autophagic vacuoles were also often seen. No normal Golgi fields were seen. These findings closely resemble those already described for feline dysautonomia. PMID- 1887444 TI - [The clinical diagnosis of protozoal myositis syndrome (Neospora caninum) of puppies]. AB - Nine puppies suffered from progressive paresis with muscle wasting, hyporeflexia and extensor rigidity. CK-activity in serum was elevated and electrodiagnostic findings were indicative of lower motor neuron disease. Although lesions were also found in the CNS, additional neurological signs were rare, but CSF examination revealed the presence of inflammatory lesions. On pathologic examination, all animals had a disseminated necrotizing myositis. In addition, a disseminated encephalomyelitis was found as well as, in 2 cases, a neuritis. In the lesions of 6 animals protozoal organisms were found which were immunocytochemically identified as Neospora caninum. Our results show that the protozoal myositis-encephalitis syndrome in puppies can be diagnosed in the clinic with high probability. A clinical differentiation between toxoplasmosis and Neospora caninum infection is presently difficult. PMID- 1887445 TI - [The age and stage of estrus in bitches with pyometra. Statistical inquiry and interpretive study of the understanding of variability]. AB - Using anamnestic data, pyometra in the bitch is shown to be particularly a disease of the older bitch in the metestral phase of cycle. Most of the patients are presented during the first four weeks after their last heat. In individual cases the disease may occur in any other stage of the cycle. The occurrence of pyometra in young bitches is discussed. An attempt is undertaken to show the pyometra endometritis complex and glandular cystic hyperplasia of the endometrium to be a similar response to different disturbances of the cycle regulation in dogs. PMID- 1887446 TI - [Malignant meningioma with lung metastases in a Boxer]. AB - The rare case of a meningioma with pulmonary metastases in a dog is described. Clinically, the ten-year-old boxer bitch showed generalized seizures, strabismus and deficient proprioception. The post-mortem examination revealed a basically localized meningeal tumor, having the light- and electron-microscopic appearance of a malignant meningotheliomatous meningioma. Immunohistochemically, the tumor cells did not show any positive reaction with antibodies to GFAP, S-100 protein, NSE, vimentin, cytokeratin, desmin, and von Willebrand factor (factor VIII related antigen). Immunohistochemical examination of seven other canine meningiomas showed an identical pattern. The results and the relevant literature are discussed. PMID- 1887447 TI - [The neuropathology of martens]. AB - The present knowledge about the neuropathologic findings and postmortem investigation methods in neurologic diseases of martens is reviewed. Following diseases are discussed: encephalitis due to viruses (rabies, distemper), bacteria (streptococcus, staphylococcus), and parasites (toxoplasmosis, hepatozoonosis, nematodes); furthermore, metabolic disorders (amyloidosis, congophilic angiopathy, calcinosis), and congenital malformations. PMID- 1887448 TI - [Myxozoa as parasites of the central nervous system of fishes]. AB - Myxosporea species in the central nervous system of fish and host-parasite interactions are described. Whereas parasites living in the nervous tissue itself do not induce clinical signs or host reactions, Myxosporea localized in neighbouring mesenchymatous tissues (blood vessels, cartilages, meninges) may induce disease of economic significance. PMID- 1887449 TI - How psychiatrists weigh risk factors when assessing suicide risk. AB - The clinical assessment of suicide risk is a difficult task that the traditional literature contributes to in a limited way. This study aims to complement the traditional literature by determining the ranking of suicide risk factors by a group of 81 psychiatrists. Hopelessness was ranked the most important risk factor, followed by Suicidal Ideation, Previous Attempts, the Level of Mood and Affect, Quality of Relationships, Signs and Symptoms of Depression, and Social Integration. Less highly ranked risk factors are also noted. The significance of these findings is discussed with respect to the literature and commonly used textbooks of psychiatry. PMID- 1887450 TI - Medical examiners and manner of death. AB - An experimental study of medical examiners in Alberta, Canada, produced manner of death determinations from simulated cases (vignettes) in order to examine interexaminer variation in certification judgments. Characteristics of medical examiners such as experience, residence, and religious background were investigated. The influence of victim characteristics was also examined, including race, age, gender, marital status, cause of death, and the presence of alcohol. Experience, residence, and religion of examiner were found to be related to judgments as were gender, medical cause of death, and the presence of alcohol. PMID- 1887451 TI - Young suicide attempters compared with a control group: psychological, affective, and attitudinal variables. AB - Suicide attempters admitted to a general hospital psychiatric ward completed questionnaires to elicit information following their suicide attempt. Compared to normal controls who had never attempted suicide, suicide attempters were significantly more hopeless, depressed, and hostile. The suicide attempts seemed to occur in response to stress. A crisis intervention model was suggested as the most appropriate way of managing these patients. PMID- 1887452 TI - American Association of Suicidology. Presidental address: suicide assessment in the 1990's. PMID- 1887453 TI - The study of suicidal lives. AB - Thirty suicides about whom book-length biographies have been written were examined in the framework of the ten statements formulated by Leenaars for each of his ten theories of suicide. Suicides who fit well with particular theories were identified, and the theories compared both for their success in describing the suicides and for their similarity with one another. PMID- 1887454 TI - Variation in suicide occurrence by time of day, day of the week, month, and lunar phase. AB - Previous studies suggest that suicide occurrence varies by month and day of the week, but not by lunar phase. Variation by time of day has never before been adequately examined; to our knowledge, all previous studies have failed to obtain time-of-death information for a large percentage of cases. We examined suicide occurrence among residents of Sacramento County, CA, during the period from 1925 to 1983. Data were abstracted from coroner's autopsy and investigative reports. In contrast to previous studies, data on time of death were available for a large percentage of cases. 4,190 suicide deaths were identified during the study period. Suicide occurrence varied substantially by time of day; for both sexes and for ages under 65 years, the fewest suicide deaths occurred during the early morning hours, from 0401 to 0800. For recent years of the study, suicides occurred most frequently on Monday for both males and females and for most age groups. Variation by month followed no consistent pattern by gender, age, years of the study, or combinations of these factors. Contrary to popular belief, suicide occurrence did not vary by lunar phase. PMID- 1887455 TI - Interpersonal loss as a factor in the suicides of alcoholics. PMID- 1887456 TI - Suicide and mass urban transit. PMID- 1887457 TI - Habits of nervous tension and suicide. AB - In a prospective study of 1,046 male medical students, those who later committed suicide showed a heightened sensitivity in stressful situations as assessed by the Habits of Nervous Tension Questionnaire (HNT). Survival analyses specified 2 of the 25 HNT items as the strongest suicide predictors: Irritability (relative risk 5.5; 95% confidence interval 1.76-17.17) and Urinary Frequency (3.3; 1.07 10.32). No other risk factors for suicide emerged from family background measures or individual medical school measures. It appears that types of sensitivity reflect psychological characteristics that are long-term precursors of suicide. PMID- 1887458 TI - The search for primary events causing the pathology in African sleeping sickness. PMID- 1887459 TI - Future health priorities and orientations of the World Health Organization in tropical health. PMID- 1887460 TI - Impact of modern technologies on tropical medicine. PMID- 1887461 TI - Travel medicine--prevention based on epidemiological data. AB - In travel medicine efforts should be concentrated on preventive measures that are necessary, and travellers should be spared the side effects, costs and stress of superfluous measures. Excess mortality abroad is mainly due to traffic and swimming accidents, indicating the need for appropriate control strategies. The morbidity in travellers to developing countries is high, and is primarily due to traveller's diarrhoea. As prophylaxis is ineffective or unrealistic, and as travellers often need fast relief, it is recommended to include loperamide and an antimicrobial agent in the travel kit. Recent studies have shown that the incidence rate per month of Plasmodium falciparum malaria in Africa may reach 24/1000. The most frequently occurring immunizable diseases are hepatitis A (3/1000) and hepatitis B (0.8/1000). For many tourists and some expatriates pre travel advice (hygiene, measures against mosquito bites, etc.) as well as chemoprophylaxis and immunization can be limited to these infections, but those travelling or staying outside large centres need additional measures. PMID- 1887462 TI - New opportunities for the diagnosis and control of animal diseases in the tropics. PMID- 1887463 TI - Anopheles vestitipennis, the probable vector of Plasmodium vivax in the Lacandon forest of Chiapas, Mexico. AB - Baseline studies to evaluate the role of different anopheline mosquitoes as probable vectors of malaria in the Lacandon rainforest region in Chiapas (Mexico) were carried out in 3 rural villages between June and November 1988. Anopheles vestitipennis was the most abundant species in all the villages, followed by An. albimanus, An. punctimacula and An. darlingi. Human bait collections showed that An. vestitipennis and An. albimanus tended to bite man either indoors or outdoors, while An. punctimacula preferred to bite outdoors. Monthly man-biting rates of An. vestitipennis tended to follow the rainfall pattern. Plasmodium vivax was detected in An. vestitipennis only, with an estimated overall infection rate of 4.67 per 1000 mosquitoes (range 0-54.42, of 3500 mosquitoes assayed). This is the first incrimination of An. vestitipennis as a probable vector of P. vivax in Mexico. PMID- 1887464 TI - Feeding behaviour and sporozoite ejection by infected Anopheles stephensi. AB - Anopheles stephensi mosquitoes infected with Plasmodium falciparum sporozoites were allowed to feed individually through fresh whole thickness mouse skin. More sporozoites were ejected into the skin in clusters than into the blood. Deposition of sporozoites in the blood was an infrequent occurrence and always coincided with ejection of these stages into the skin--perhaps a spill-over effect. The number of probes before feeding (median 4.5) was not correlated with the sporozoite inoculum (median 8), nor was the number of sporozoites in the glands (median 14,500). However, the number of sporozoite clusters in the skin (median 1) was positively correlated with the inoculum size. The median value of the sporozoite inoculum was 22, when only those mosquitoes that ejected sporozoites were included. When feeding was interrupted and recommended on a new membrane, sporozoite ejection occurred with equal frequency on both occasions. Sporozoites disappeared from the site of bites in living mice within 2 h of feeding. The epidemiological significance of these observations is discussed. PMID- 1887465 TI - Permethrin-impregnated curtains in malaria control. AB - The impact of permethrin-impregnated curtains on the incidence of malaria episodes, parasitaemia and splenomegaly was assessed during a 22 month period in 2 groups of children aged 0.5-6 years. One group lived in houses where permethrin impregnated curtains had been installed, the other group lived in houses without curtains. A significant reduction of incidence of malaria episodes, mean parasite density, parasite prevalence and splenomegaly was consistently observed in the intervention group towards the end of the period of moderate transmission, whereas no clear-cut impact could be demonstrated during the high transmission period. The influence of malaria pressure and community utilization on the protective efficiency of curtains is discussed. Because of their acceptability and the ease of reimpregnation, curtains proved to be a suitable technique for integration into primary health care. PMID- 1887466 TI - Comparison of two simple methods for determining malaria parasite density. AB - Two simple methods for determining malaria parasite density which require only the examination of a thick blood film were compared with a more accurate method which involves determination of the red blood cell count and measurement of the level of infection in red blood cells by examination of a thin blood film. In one method, the number of parasites present per white blood cell is counted and this figure multiplied by 8000 (an average white blood cell count per microliter) to give the parasite density. In the other method, the number of parasites present per high power microscope field is determined and the parasite density calculated from this value and the assumed volume of blood present in one high power field. The latter method proved to be more accurate than that based on determination of the parasite/white blood cell ratio, probably because the variability in the volume of blood used in preparation of thick blood films was less than the variability of the white blood cell count in the population studied. PMID- 1887467 TI - The metabolic response to rapid intravenous glucose injection in acute falciparum malaria. AB - Because hypoglycaemia is common in severe malaria, intravenous glucose is often given empirically to patients on admission to hospital. To investigate the metabolic response to rapid glucose injection in acute malaria, 50 ml of 50% w/v (25 g) dextrose was given over 5 min to 10 adult patients (7 males, 3 females; mean age 30 years) with acute falciparum malaria. Five patients with severe infections were studied between doses of intravenous quinine; 5 cases were uncomplicated and previously untreated. The patients with severe malaria had lower pre-injection plasma glucose concentrations than patients with uncomplicated infections (mean +/- standard deviation, 4.2 +/- 0.9 vs 5.8 +/- 1.1 mmol/litre, 2P less than 0.015). However, peak glucose concentrations (18.6 +/- 4.8 vs 17.0 +/- 2.4 mmol/litre) and integrated responses (AUC0-245 min) were similar in the groups (2P greater than 0.1 in each case), and pre- and post injection plasma insulin concentrations and AUC0-245 min values were also not significantly different (2P greater than 0.05 in each case). No 'rebound' hypoglycaemia was observed. The patients with severe malaria had higher peak plasma lactate concentrations than the uncomplicated patients (2.5 +/- 0.7 vs 1.5 +/- 0.9 mmol/litre, 2P less than 0.05), but the highest plasma lactate achieved and the greatest maximum post-injection rise were only 3.8 and 0.8 mmol/litre respectively. The average maximum reduction in plasma potassium after injection was 0.2 mmol/litre at 35 min. These data suggest that injections of hypertonic dextrose given empirically in conventional doses to non-acidotic patients with acute, severe malaria are not harmful, but the metabolic response in patients with an established acidosis remains unknown. PMID- 1887468 TI - The changing pattern of Plasmodium falciparum susceptibility to chloroquine but not to mefloquine in a mesoendemic area of Somalia. AB - The response of Plasmodium falciparum to chloroquine and mefloquine was investigated in a mesoendemic area of Somalia from 1986 to 1989. Serial in vivo field tests for chloroquine sensitivity were performed and the sensitivity in vitro to chloroquine and mefloquine was evaluated using the standard WHO in vitro microtest. Chloroquine treatment in vivo (25 mg base/kg body weight) resulted in parasite clearance in all patients within 7 d (S/RI) in 1986, while 17%, 19% and 30% RII/RIII responses were found in 1987, 1988 and 1989 respectively. There was consistent increase of parasite clearance time of the S/RI cases in all years. The sensitivity study in vitro in 1986 showed a low degree of chloroquine resistance in 3 of 29 isolates tested and a mean 50% effective dose (EC50) and EC99 of 0.34 x 10(-6) M and 1.99 x 10(-6) M, respectively. In contrast, in 1989, 12 of the 19 isolates tested were resistant to chloroquine. The mean EC50 and EC99 values had increased to 0.78 x 10(-6) M and 7.50 x 10(-6) M respectively. The data in vivo and in vitro indicate a rapid increase of chloroquine resistance both in frequency and degree. All isolates tested in 1986 and 1989 were fully inhibited by mefloquine at 3.2 x 10(-6) M, suggesting full sensitivity. Thus, increased resistance of P. falciparum to chloroquine did not significantly influence the sensitivity pattern of mefloquine. PMID- 1887469 TI - Reversal of chloroquine resistance with cyproheptadine in 'wild' strains of Plasmodium falciparum. PMID- 1887470 TI - In vivo-in vitro test for chloroquine potentiation by cyproheptadine against Plasmodium falciparum. PMID- 1887471 TI - Absence of antimalarial activity or interaction with mefloquine enantiomers in vitro of the main human metabolite of mefloquine. PMID- 1887472 TI - Comparative effectiveness of artemisinin suppositories and oral quinine in children with acute falciparum malaria. PMID- 1887473 TI - A double-blind study on the efficacy of oral dapsone in cutaneous leishmaniasis. AB - One hundred and twenty patients with localized cutaneous leishmaniasis were randomly allocated to receive tablets of dapsone (100 mg) or matching placebo tablets every 12 h for 6 weeks. No topical medication was used. Demonstration of Leishmania from skin lesions by the slit smear technique was mandatory for inclusion. Before, periodically during, and one month after completion of therapy an overall clinical assessment, haemoglobin determination, leucocyte count, and liver function tests were performed. 49 patients (82%) of those receiving dapsone were assessed as cured by clinical and parasitological criteria. Oral dapsone has certain advantages over other current forms of treatment: it is economical and widely available in countries where cutaneous leishmaniasis is common, and it is effective by mouth and well tolerated. PMID- 1887474 TI - Isoenzyme characterization of Leishmania from man, dog and sandflies in the Maltese islands. AB - As a part of a general survey on leishmaniases and sandflies of the Maltese islands, 22 Leishmania stocks were isolated from human visceral (1) and cutaneous (1) cases, dogs (16) and sandflies (4). They were characterized by the analysis of 15 enzymes. The commonest Mediterranean L. infantum zymodeme, MON 1, was found to cause human and canine visceral leishmaniasis; L. infantum MON 78, which has so far been isolated only in Malta, was the agent of human cutaneous leishmaniasis. Both zymodemes were isolated from the same sandfly species, Phlebotomus perniciosus. PMID- 1887475 TI - Monoclonal antibodies for the identification of New World Leishmania. PMID- 1887476 TI - Spontaneous clinical resolution without specific treatment in mucosal leishmaniasis. PMID- 1887477 TI - African trypanosomiasis and drug-induced encephalopathy: risk factors and pathogenesis. AB - Data on 598 patients with Trypanosoma brucei gambiense sleeping sickness, with abnormal cerebrospinal fluid (CSF) and treated with melarsoprol, were reviewed to determine risk factors for drug-induced encephalopathy. The incidence of melarsoprol-induced encephalopathy was increased in patients with trypanosomes present in the CSF, in patients with a high CSF lymphocyte count, and among patients in whom no trypanosomes were found in either the blood or the lymph node aspirate. Among patients with trypanosomes in the CSF, the risk of encephalopathy was similar whether or not they also had trypanosomes seen in the haemolymphatic system. Dimercaprol, a heavy metal chelator, did not reduce the case-fatality rate of patients with encephalopathy. These observations and others are compatible with the hypothesis that an immune phenomenon is involved in the pathogenesis of melarsoprol-induced encephalopathy. Whether the basic mechanism relates to deposits of immune complexes in the central nervous system or to the release of trypanosomal antigens which subsequently bind to brain cells and attract antibodies or T lymphocytes, the rapidity with which trypanosomal antigens are released may be critical, and very aggressive therapeutic schemes may result in higher toxicity, especially in patients with an impaired blood brain barrier. PMID- 1887478 TI - Toxoplasma serology in Zambian and Ugandan patients infected with the human immunodeficiency virus. AB - In the USA and Europe, toxoplasmosis is well recognized as an important cause of morbidity and mortality among immunocompromised individuals. Toxoplasma gondii has been shown to be a common opportunistic infection in patients infected with the human immunodeficiency virus (HIV) in the USA and Europe with published estimates ranging from 20% to 80%. The importance of Toxoplasma infection in East Africa has not yet been defined. The seroprevalence rates of toxoplasmosis in Zambian and Ugandan patients were determined using the dye test (DT) and the latex agglutination test (LAT). The geographical variation in seroprevalence rates noted in western countries was also found in these African countries, with Zambia showing significantly lower rates than Uganda. 34% of Ugandan (64/186) and 4% of Zambian (8/187) patients infected with HIV, compared with 27% of Ugandan (26/93) and 11% of Zambian (20/189) HIV-negative persons, had anti-Toxoplasma immunoglobulin G antibodies. With the LAT, 13% of the Ugandan and 7% of the Zambian sera gave a false positive result. The relevance of Toxoplasma serology in Africa is discussed. PMID- 1887479 TI - Occurrence of Schistosoma mattheei-like eggs in a spinal cord lesion. PMID- 1887480 TI - Five mammalian schistosome species in an endemic focus in India. PMID- 1887481 TI - Hookworm (Necator americanus) infection and storage iron depletion. AB - The relationship between iron status and the intensity of infection with hookworm was investigated in a rural population on Karkar Island, Mandang Province, Papua New Guinea. There was a significant negative correlation between plasma ferritin level and hookworm burden, which was strongest in males. In contrast, there was no correlation between plasma ferritin and hookworm egg count, and no consistent correlation between haemoglobin level or haematocrit and either measure of hookworm intensity. The results suggest that the role of hookworm in the aetiology of anaemia may be difficult to assess without the accurate measurement of hookworm burden. PMID- 1887482 TI - Detection of antibodies against Echinococcus granulosus major antigens and their subunits by immunoblotting. AB - An immunoblot assay was tested to evaluate its ability to diagnose human hydatidosis and to analyse the reactivity of hydatid patients' sera with the subunits of the 2 major Echinococcus granulosus antigens (5 and B). In all, 308 sera were examined: 166 sera from patients with clinically diagnosed hydatidosis, 100 sera from healthy control subjects, and 42 sera from patients with diseases other than hydatidosis. The sensitivity of the method was 90%, as compared to 78% with the immunoelectrophoresis/double diffusion test for antigen 5. No reactivity was found with 15 sera from patients with schistosomiasis, 7 sera from patients with trichinellosis, or 20 sera from patients with non-parasitic diseases. Analysis of serum reactivities showed the presence in all positive sera of antibodies directed against the 39 kDa molecule of the antigen 5 complex. A lower reactivity (55% of all hydatid sera) was observed with the subunits of the antigen B complex. PMID- 1887483 TI - Albendazole versus praziquantel in the treatment of cerebral cysticercosis: clinical evaluation. AB - One hundred consecutive patients presenting with symptoms and signs of neurocysticercosis, confirmed by neuroimaging techniques, were randomly assigned to treatment with either praziquantel 50 mg/kg/d for 15 d or albendazole 15 mg/kg/d for 30 d. All patients were treated in addition with steroids for 45 d. Follow-up was for 90 d for response to treatment and at least 1 year for recurrence. Although similar numbers of patients showed no improvement in neuroimaging criteria at 3 months, the response to albendazole was more pronounced with larger numbers showing marked improvement or disappearance of lesions. Resolution of the presenting neurological signs and symptoms was also more frequent in the albendazole group. Electroencephalographic changes also became normal. The use of steroid cover eliminated the headache frequently present during the first few days of treatment and permitted severe cases to be treated. Both albendazole and praziquantel appeared to be effective at the doses used, with albendazole showing a slightly better overall response. PMID- 1887484 TI - Diagnostic identification of Taenia saginata with the polymerase chain reaction. PMID- 1887485 TI - Prevalence of Enterobius vermicularis in man in Malaysia. PMID- 1887486 TI - The significance of low density microfilaraemia in the transmission of Wuchereria bancrofti by Culex (Culex) quinquefasciatus Say in Sri Lanka. AB - Laboratory-bred Culex quinquefasciatus were fed on carriers with low and moderate densities of microfilariae (mf) of Wuchereria bancrofti. In the first series of experiments, mosquitoes were dissected 12 d after feeding. The percentage of infected mosquitoes and the numbers of larvae per infected mosquito were directly proportional to the mf density at the time of feeding. There was an overall high infection rate and a wide distribution of larvae per individual mosquito at all levels, except for the 4 lowest counts. Of the 4 carriers with counts of 5 mf/ml and less, 3 were capable of infecting Cx quinquefasciatus, giving infection rates of 1.0%, 7.4% and 12.0% respectively. In the second series, some mosquitoes were dissected immediately after feeding and the remainder 12 d later. There was a good correlation between the number of mf ingested and the number of infective larvae per mosquito. The high infection rates in Cx quinquefasciatus when fed on low-density microfilaraemia carriers, and the varying number of larvae in individual mosquitoes, suggest that low-density carriers could be a source of infection. Field studies were also carried out in 3 different area with mf rates of 7.24%, 0.72% and 0.16%, respectively. In the 2 areas with low mf rates, infection rates in mosquitoes were 1.32% and 1.08% respectively. Cx quinquefasciatus fed on a carrier with a residual microfilaraemia of 19 mf/ml following treatment with diethylcarbamazine had an infection rate of 13.8%. These studies suggest that the examination of recently fed house-resting populations of Cx quinquefasciatus could be a sensitive method for measuring the prevalence of mf in the human population. PMID- 1887487 TI - The dynamics of infection and disease in bancroftian filariasis. AB - This study examines the relationship between the dynamic of Wuchereria bancrofti infection and the development of chronic lymphatic disease. Data sets from Pondicherry, south India, and Calcutta are used to estimate the age-specific proportion of the endemic population which has converted from microfilaria positive to amicrofilaraemia, and is assumed to be at risk of disease. For men, but not women, the age-prevalence profile of the estimated population 'at risk' is shown to correspond closely to the observed age-prevalence of chronic lymphatic disease in the same community. For both sexes, and independent of age, approximately 11% of the population at risk eventually develop lymphoedema. These observations suggest that filariasis endemic populations consist of those individuals who remain amicrofilaraemic and asymptomatic, and those who progress through the sequence: uninfected, microfilaraemic, amicrofilaraemic, to develop irreversible obstructive lymphatic pathology. PMID- 1887488 TI - Clinical epidemiology of bancroftian filariasis: effect of age and gender. AB - A cross-sectional survey was used to determine the prevalence of disease (n = 6493) and microfilaraemia (n = 24,946) due to Wuchereria bancrofti in Pondicherry, south India. The total disease attributable to filariasis was significantly higher in males (13.67%) than females (2.26%), due to the occurrence of hydrocele in males. While the prevalence of chronic signs was clearly age-dependent in both sexes, that of acute signs was independent of age. Thus the age and gender structure of the survey sample will crucially influence apparent prevalence. Examination of the gender differences in the point prevalence of disease in 12 areas of India showed a significant relationship between occurrence of disease and gender, but this relationship did not significantly differ between northern and southern Indian populations. The study suggested that the failure to appreciate the importance of age and gender in disease prevalence has led to misconception about disease patterns in India. PMID- 1887489 TI - Tolerance of single high-dose ivermectin for treatment of lymphatic filariasis. PMID- 1887490 TI - Changes in ocular onchocerciasis after two rounds of community-based ivermectin treatment in a holo-endemic onchocerciasis focus. AB - In a longitudinal study to determine the effect of annual community-based treatment of ocular onchocerciasis with ivermectin, the population living in the 3 most affected villages in the holo-endemic onchocerciasis focus of Asubende in Ghana were re-examined 16 and 24 months after initiating treatment. Ocular microfilarial loads had decreased to very low levels in nearly all of the 334 examined persons who were treated twice. Only very few subjects had ocular loads of 32 microfilariae or more in the anterior chamber of the eye, but this was not associated with deterioration of ocular lesions. Important regression of both early and advanced lesions of the anterior segment of the eye was observed, which was highly statistically significant with respect to iridocyclitis. Lesions of the posterior segment of the eye remained stable. Though no systematic change in the visual acuity of the population was observed, 3 new cases of blindness occurred in persons who already had eye lesions at such an advanced stage that ivermectin treatment could no longer affect the outcome. The results suggest that annual ivermectin treatment is adequate to control onchocercal ocular disease even in populations with very high endemicity levels. PMID- 1887491 TI - Geohelminth infection and academic assessment in Jamaican children. PMID- 1887492 TI - The epidemiological implications of a multiple-infection approach to the control of human helminth infections. AB - It has been suggested that there is economic advantage in using a single community therapy programme to deliver multiple treatments against several parasitic infections. This preliminary study estimates the occurrence of concurrent helminth infection in Africa and Brazil to determine whether such an approach is justified epidemiologically. The results indicate that the occurrence of geohelminthiasis with schistosomiasis is sufficiently frequent in some areas of both Africa and Brazil for a combined approach to control to be appropriate, but that the relatively low frequency of occurrence of onchocerciasis with other infections would justify a multi-infection approach to control at specific foci only. PMID- 1887493 TI - Serological responses in primary neuritic leprosy. AB - The serological responses to 2 Mycobacterium leprae specific epitopes and one common mycobacterial antigen were examined in 46 untreated patients with primary neuritic (PN) leprosy. M. leprae specific antibodies to the terminal disaccharide of phenolic glycolipid and/or the ML-04 defined epitope on the 35 kDa protein were detected in 41% of PN patients and 47% responded to one of the 3 antigens. This serological response mirrored that observed in paucibacillary leprosy patients. There was a significant increase in the level of antibody response when more nerve trunks were involved. Changes in antibody levels in seropositive PN patients may prove useful in monitoring the response to chemotherapy. PMID- 1887494 TI - Outbreak of typhoid fever due to multiresistant Salmonella typhi in northern India--a preliminary report. PMID- 1887495 TI - Hemichorea in enteric fever. PMID- 1887496 TI - Human leptospirosis: a recent study in Madras, India. PMID- 1887497 TI - Isolation of Yersinia enterocolitica in Alexandria, Egypt. PMID- 1887498 TI - Pyoderma in Israel due to Streptococcus pyogenes M type 'Potter C'. PMID- 1887499 TI - Tungiasis in Trinidad: case report. PMID- 1887500 TI - The Marrara syndrome: isolation of Linguatula serrata nymphs from a patient and the viscera of goats. PMID- 1887501 TI - Studying DNA modifications and DNA-protein interactions in vivo. A window onto the native genome. AB - The study of native genomes has been greatly facilitated by the use of direct genomic sequencing and footprinting strategies. This review provides an overview of the techniques involved and presents some highlights of the biological results obtained with these methods. PMID- 1887502 TI - Cell type specification during sea urchin development. AB - Recent discoveries indicate that cell lineages and fates play a key role in the establishment of spatially restricted gene expression during sea urchin development. Unique sets of founder cells generate five territories of gene expression by means of an invariant pattern of complete cleavage. Cell lineage analysis demonstrates that the second embryonic axis, the oral-aboral axis, is specified with reference to the first cleavage plane. In the undisturbed embryo, clones that contribute to one territory or another begin to appear at the third cleavage, and founder cell segregation to all five territories is completed by the sixth cleavage. Founder cell segregation is a key feature of mechanisms that establish the spatially defined gene activity of sea urchin embryogenesis. PMID- 1887503 TI - Minor histocompatibility antigens. AB - Histocompatibility antigens have been studied for over 50 years because they form a major obstacle to clinical transplantation. Human minor histocompatibility antigens remain ill-defined, but minor histocompatibility loci have been mapped on nearly every mouse chromosome. Recent molecular definition of several transplantation antigens suggests that they are by-products of an immune system poised to present viral antigens, and a mutation in any gene may give rise to a new minor histocompatibility antigen. PMID- 1887504 TI - Control of ColE1 plasmid replication by antisense RNA. AB - One of the two major classes of regulatory strategies that control plasmid copy number involves recognition via base pairing between two plasmid-encoded complementary RNAs. The detailed analysis of this control circuitry has revealed some features of regulatory mechanisms based on RNA-RNA interaction that distinguish them from those based on protein-nucleic acid interaction. These features provide a framework with which to understand other regulatory mechanisms based on RNA-RNA interaction, and will aid in the design of efficient artificial antisense RNA systems. PMID- 1887505 TI - Duplex Doppler sonography of the umbilical arteries: predictive value in IUGR and correlation with birth weight. AB - Forty-three women with either clinically high-risk singleton pregnancies or a predicted fetal weight less than the 10th percentile were studied in their third trimester by duplex Doppler sonography of the free umbilical artery to assess the associations between umbilical arterial flow resistance and intrauterine growth retardation (IUGR) and birth weight. Test criteria included: the greatest (GRI), mean (MRI), and least (LRI) resistive index. The criterion with the strongest association with IUGR (p = 0.001) was the parameter of the LRI predicting IUGR). Linear regression analysis showed a nonsignificant correlation between RI and percentile birth weight, with r2 = 0.05 and p = 0.131. While significant associations can be shown between RI and IUGR, the clinical use of the results of this test should reflect the imprecise nature of these correlations. PMID- 1887506 TI - Computer analysis and pattern recognition of Doppler blood flow spectra for disease classification in the lower limb arteries. AB - In the present study, a computer processing method was developed to objectively classify disease in the lower limb arteries evaluated by noninvasive ultrasonic duplex scanning. This method analyzes Doppler blood flow signals, extracts diagnostic features from Doppler spectrograms and classifies the severity of the disease into three categories of diameter reduction (0-19%, 20-49% and 50-99%). The features investigated were based on frequency features obtained at peak systole, spectral broadening indices and normalized amplitudes of the power spectrogram computed in various positive and negative frequency bands. A total of 379 arterial segments studied from the aorta to the popliteal artery were classified using a pattern recognition method based on the Bayes model. Two classification schemes using a two-node decision rule were tested. Both schemes gave similar results, the first one provided an overall accuracy of 83% (Kappa = 0.42) and the second an overall accuracy of 81% (Kappa = 0.35) when compared with conventional biplane contrast arteriography. These performances, especially for the 0 to 19% lesion category, are better than the one obtained by the technologist (accuracy = 76% and Kappa = 0.33), based on visual interpretation of the Doppler spectrograms. To recognize hemodynamically significant stenoses (50 99% lesions), the pattern recognition system has a sensitivity and a specificity of 50% and 99%, respectively, using classification scheme I. With classification scheme II, the sensitivity and the specificity are 50% and 98%, respectively. Visual interpretation of the Doppler spectrograms leads to a sensitivity and a specificity of 50% and 98%, respectively. These results are the first to be obtained by a pattern recognition system in classifying lower limb arterial stenoses. PMID- 1887507 TI - Measurement of intima-media thickness of common carotid arteries with high resolution B-mode ultrasonography: inter- and intra-observer variability. AB - High-resolution B-mode ultrasonography enables quantitative measurement of the thickness of the intima-media layer of superficial large arteries noninvasively. We investigated the inter- and intra-observer variability of this measurement in the common carotid arteries in 10 randomly selected men. The maximal right and left carotid intima-media thickness (IMT) was measured with calipers during the scanning from frozen images by four observers in a blinded fashion. Three observers also repeated the scanning and the measurements twice with a week's intervals, with no knowledge of the previous readings. The inter-observer coefficient of variation (CV) was 10.5%. The intra-observer CV (mean of right and left CCA) was 5.4-5.8% for the three observers who carried out the measurements three times. The mean absolute difference between the first and third measurement was 0.087 mm. The intra-observer variation accounted for only 4% of the total measurement variability, 96% being attributable to inter-observer variation. These data show that most of the measurement variability in ultrasonographic B mode IMT measurements is due to differences between observers, whereas the within observer variability over time appears proportionately very small. PMID- 1887508 TI - Ultrasound properties of liver with and without particulate contrast agents. AB - Basic acoustic parameters are examined in rabbit liver with and without a solid contrast agent used for tumor detection. In normal liver, backscatter, attenuation, and sound speed are found to decrease with increasing water content. The addition of micron-sized particles made from iodipamide ethyl ester (IDE) can increase backscatter and attenuation depending on size and concentration. A discrepancy of the increased backscatter from theoretical predictions based on random scatterers is attributed to the particle's biodistribution in the liver. PMID- 1887509 TI - The mechanisms of stone disintegration by shock waves. AB - Through interpretation of high-speed films at 10,000 frames per second of shock wave action on kidney stones and gallstones, the mechanism of stone destruction was analyzed in detail. This shows that the interaction of the shock wave with the targets firstly produces fissures in the stone material. Liquid then enters these small cracks. The actual disintegration is caused later by the enormous violence of imploding cavitation bubbles within these small split lines. That cavitation acts inside the stone and causes fragmentation even within the human gallbladder could furthermore be demonstrated by using scanning electron microscopy. These results should lead to a different process in gallstone lithotripsy leaving intervals between the shock wave treatments. This will allow the viscous bile fluids to occupy the fissures of the stones more completely and, therefore, should increase the cavitational activity on the subsequent treatment with shock pulses. PMID- 1887510 TI - Theoretical predictions of the acoustic pressure generated by a shock wave lithotripter. AB - A one-dimensional frequency domain model is used to predict the temporal peak acoustic pressures developed near the beam focus during extracorporeal shock wave lithotripsy (ESWL). The model includes consideration of finite amplitude effects, attenuation, diffraction and dispersion, and results are presented for the case of an electrohydraulic source with the beam geometry of the Dornier HM3 lithotripter. Propagation in castor oil, water and tissue is examined. The model predicts that nonlinear effects enhance the peak positive pressure (p+) at the beam focus in 6 cm of tissue in a Dornier type lithotripter by a factor of about 3 above that which would be expected for linear propagation. The negative peak pressure (p-), conversely, is predicted to be depressed by a factor of about 0.7 below the linear theory prediction. The model also indicates the occurrence of excess absorption due to shock formation. This is shown, for a Dornier HM3 type lithotripter, to cause a reduction in the peak positive pressure gain and a broadening of the focal depth as the output of the source is increased. A threshold aperture pressure is identified for a source with the same beam geometry as the Dornier HM3 below which shock formation does not occur. In this region the pressure gain increases and the focal depth narrows as the source output increases. These effects are characteristic of current commercial piezoelectric and electromagnetic lithotripsy fields. PMID- 1887511 TI - In situ exposimetry: the ovarian ultrasound examination. AB - We have constructed a specialized in vivo exposimetry system and developed and tested customized software using specially fabricated hydrophones. We placed the hydrophones in the lateral vaginal fornix as close to the ovary as possible (usually 1-2 cm from the ovary) and determined selected first-order and second order ultrasonic field quantities during a routine ultrasound examination of the ovary. Our sonographic measurements yielded mean ultrasound beam path distances of 7.6 cm. (n = 18) in the presence of a distended bladder and 7.0 cm. (n = 25) in the presence of an empty bladder with an average group insertion loss of 6.2 dB and 7.3 dB, respectively. Using a Fixed Attenuation Model, the tissue attenuation coefficient value was 2.98 dB/MHz; whereas for the Overlying Tissue Model the value was 0.72 dB/cm-MHz. These data are both specific and unique in that they have been systematically obtained in situ. PMID- 1887512 TI - Pulse-echo imaging using a nondiffracting beam transducer. AB - Conventional ultrasonic transducers generate beams that diffract as they travel. This phenomenon causes images produced in B-mode to be degraded in the far-field of the transducers. Focused transducers are used to improve image quality. Unfortunately, focused transducers have short depth of field. Although multiple pulse transmissions focused at several depths are used to increase the effective depth of field, imaging frame rate is reduced dramatically leading to blurred images of moving objects such as the heart. We present a family of transducers that produce nondiffracting beams of large depth of field. Therefore, uniformly high resolution throughout the imaging area can be obtained without sacrificing the imaging frame rate. In addition, the nondiffracting property of these beams makes the correction for beam diffraction negligible in tissue characterization. This paper reports the results of computer simulations as well as in vitro and in vivo pulse-echo imaging experiments with a nondiffracting transducer. Images are compared to those obtained by conventional focused Gaussian shaded beam transducers and a commercial ACUSON 128 B-scanner. The new transducer has much longer depth of field with higher sidelobes than conventional transducers of the same aperture. Sidelobes can be reduced using the new transducer to transmit and the dynamically focused transducer to receive. PMID- 1887513 TI - Combined reflection and transmission ultrasound imaging. AB - Reflex transmission imaging (RTI) is a method for producing orthographic ultrasound transmission images, which depict focal-plane transmittance, by using a single transducer rather than an opposed transducer pair. RTI can be implemented using modified B-scan equipment, and a bidirectional scan probe. It has the further advantage of enabling simultaneous generation of integrated reflection C-scan (IRCS) images, which depict backscatter from the focal plane, in perfect registration with the transmission images. We describe these methods, demonstrate a new process by which the reflection and transmission images can be combined to produce a new image of superior quality, and demonstrate the applicability of this technique to improved visualization of kidney stones, with potential application to lithotripsy. PMID- 1887514 TI - Volume measurement by ultrasonic transverse or sagittal cross-sectional scanning. AB - A technique is described that provides an accurate estimation of the volume of an organ from its ultrasonic cross-sectional images. The technique is applied to two types of ultrasonic investigation, one providing transverse and the other sagittal images. The organ outline has to be traced on each scan. The computer first calculates the area and then the volume from the vector areas and the centroids of a series of sections. The technique has been tested with phantoms of various shapes and volumes made with agar gel. These experiments show that the error in the volume estimation is less than 10% and the variability of measurements is less than 2%. PMID- 1887515 TI - Sonoluminescence in water and agar gels during irradiation with 0.75 MHz continuous-wave ultrasound. AB - Free radicals, detected as light emissions (sonoluminescence), can be produced in both simple aqueous systems and agar gels by irradiation with 0.75 MHz continuous wave (CW) ultrasound using acoustic pressures as low as 200 KPa. Although the acoustic pressures necessary for free radical formation in tap water gels (200 KPa), are considerably higher than those required for the formation of macroscopic visible bubbles (26 KPa), the sonoluminescence threshold (0.5 W/cm-2 SATA equivalent) falls at the lower end of the intensity range (0.5-3 W/cm-2) commonly used by ultrasonic physiotherapy equipment. In respect of the overall features of cavitation processes, agar gels appear to be suitable simple systems in which to model cavitation in vivo. However, cavitation processes leading to sonoluminescence are themselves complex as illustrated by the findings that small changes in ionic composition or pH have a significant effect on both the acoustic pressure threshold and the extent of sonoluminescence above this threshold. PMID- 1887516 TI - O2 pressures between 0.12 and 2.5 atm abs, circulatory function, and N2 elimination. AB - To study the effects of inhaled oxygen pressures on N2 elimination, 72, 2-h washouts were performed in 6 subjects at oxygen pressures of 0.12, 0.2, 1.0, 2.0, and 2.5 atm abs using a closed circuit system that supplied an O2-argon mixture and collected the N2 off-gassed. Hypoxia induced a significant (9.4%, P less than 0.05) increase in nitrogen eliminated as compared to normoxia. Pure oxygen breathing induced a small, insignificant (3.5%) decrease in nitrogen yields, but further increases in oxygen pressure induced significant decreases in nitrogen yields (-8.9% and -16.9% for 2.0 and 2.5 atm abs, respectively). Heart rate, cardiac output, skin perfusion and leg blood flow decreased, whereas mean arterial pressure increased with increasing oxygen pressure. We conclude, therefore, that perfusion-dependent N2 elimination decreases secondary to vasoconstriction induced by increasing oxygen pressures. Changes in inhaled oxygen pressures during different phases of compression-decompression may induce alterations in the rate of inert gas uptake and elimination. Although not currently quantifiable, such alterations would imply added uncertainties in the computation of decompression schedules. Oxygen breathing during decompression should be performed at the lowest possible ambient pressure compatible with freedom from pathogenic bubble formation. PMID- 1887517 TI - Venous gas emboli and complement activation after deep repetitive air diving. AB - Complement activity has been linked to decompression sickness (DCS), but the effects of intravascular bubbles on complement activation are poorly understood. We have investigated intravascular complement activation by measuring red blood cell (RBC)-bound C3d after repetitive air diving in man. Subjects were exposed to a single, 20 min, 170 fsw (feet of sea water) dive, or to 2 such dives with a 6-h surface interval. Doppler monitoring for venous gas emboli was performed postdive. Predive blood samples were studied to determine sensitivity of complement to activation by air bubbles. Other predive and postdive venous samples were evaluated for intravascular complement activation. No cases of DCS occurred in 39 dives. Baseline complement sensitivity appeared normally distributed, thus "sensitive" and "insensitive" subjects were not clearly distinguishable. RBC-bound C3d did not increase after 1 dive but did increase after the repetitive dive (P less than 0.05). Furthermore, maximum bubble grade was independent of complement activation. PMID- 1887518 TI - High altitude dives from 7000 to 14,200 feet in the Himalayas. AB - Indian Navy divers carried out no-decompression dives at altitudes of 7000 to 14,200 ft (2134-4328 m) in the Nilgiris and Himalayas from May to July 1988. Seventy-eight dives on air and 22 dives on oxygen were carried out at various altitudes. The final dives were at Lake Pangong Tso (4328 m) in Ladakh, Himalayas, to a maximum of 140 feet of sea water (fsw) [42.6 meters of sea water (msw)] equivalent ocean depth in minimum water temperature of 2 degrees C. Oxygen diving at 14,200 ft (4328 m) was not successful. Aspects considered were altitude adaptation, diminished air pressure diving, hypothermia, and remote area survival. Depths at altitude were converted to depths at sea level and were applied to the Royal Navy air tables. Altitude-related manifestations, hypoxia, hypothermia, suspected oxygen toxicity, and equipment failure were observed. It is concluded that stress is due to effects of altitude and cold on man and equipment, as well as changes in diving procedures when diving at high altitudes. Equivalent air depths when applied to Royal Navy tables could be considered a safe method for diving at altitudes. PMID- 1887519 TI - Decompression comparison of N2 and O2 in rats. AB - We have previously reported that O2 in the breathing gas mixture contributed significantly to the risk of decompression sickness (DCS) in rats after rapid (less than 10 s) decompression to the surface from depth. The rate of O2 uptake was extremely fast (less than 1 min estimated for equilibrium after a pressure change) compared to much slower rates for He and N2. To further define the role that O2 plays in diving, the present investigation examined decompression outcome in unanesthetized male albino rats after 60-min N2-O2 dives (1-3 atm abs O2, depth 6.26 or 7.26 atm abs). Slower decompression profiles were used to determine the elimination rates of N2 and O2 as pressure was reduced and included "stops" of up to 20 min. The probability of DCS was modeled using the maximum likelihood technique. O2 again contributed significantly to the risk of DCS, although O2 was eliminated very rapidly during decompression; the washout of N2 was considerably longer. These findings support the view that O2 can add significantly to decompression risk. However, this phenomenon may not normally be encountered during human diving operations where relatively slower decompression and lower PO2's are used. PMID- 1887520 TI - Simulation of the dynamics of decompression sickness bubbles and the generation of new bubbles. AB - This communication introduces a system of equations for simulating the dynamics of growth and decay of decompression bubbles. The equations are solved by a numerical method and account for gas diffusion, the action of surface tension, tissue N2 washout by blood, and the rate of ascent from depth. The simulations demonstrate how inward diffusion of N2 can generate a persistent gas bubble from a nucleation process or a nucleus (these are provisionally defined as entities that can give rise to a small bubble of a certain size); an explosive positive feedback loop is set off as the enlarging radius decreases the pressure due to surface tension. Generation of persistent bubbles is most likely during ascent from depth when PN2 inside any gas phase is decreasing rapidly and PN2 outside is still high before appreciable tissue washout has occurred. The "susceptibility" for the generation of a persistent bubble at any time can be defined as the reciprocal of the difference, at that time, between partial pressure of the nitrogen in tissue and in a spherical bubble of the size that is characteristic of the nucleation process or nucleus; susceptibility is less when ascent is slow because PN2 in bubbles stays high while washout removes N2 from the tissue. PMID- 1887521 TI - Wheezing in a commercial diver due to disinfectant. AB - A case is described of a saturation diver with no previous history of asthma who repeatedly developed work-related symptoms of asthma at pressure, which appear to be causally related to the use of dichlorophen as a disinfectant agent. Although challenge tests were negative, suggesting that dichlorophen may have been acting as an irritant rather than as a sensitizer, the symptoms were abolished by the use of an alternative disinfectant agent. The potential importance of this effect in a diver is discussed, and the case highlights the importance of the use of nontoxic agents in the diving environment. PMID- 1887523 TI - Crystal growth of calcium oxalate in urine of stone-formers and normal controls. AB - In this study, the relative crystal growth rate (Vcr) of calcium oxalate (Caox) and a number of other parameters were determined in 17-h daily (d) and 7-h nocturnal fractions (n) of whole urine from 20 recurrent Caox stone formers (SF) and 29 age-matched male normal controls (NC). Vcr, which was determined by the gel crystallization method (GCM), showed the largest difference between SF and NC among all parameters under investigation. Mean values (+/- SD) obtained for Vcr were: 0.73 +/- 0.58 (SF-d)/0.21 +/- 0.22 (NC-d; P less than 0.001) and 0.63+/- 0.58 (SF-n)/0.24 +/- 0.25 (NC-n; P less than 0.01). Significantly higher concentrations of Ca and lower concentrations of thermodynamic and kinetic effectors of Caox crystal growth were responsible for the higher crystal growth rates observed in SF as compared with NC, i.e., they should be partially causative in Caox urolithiasis. However, other properties of urine or the urinary tract (potentially, crystal agglomeration and adhesion) must be accounted for in the genesis of Caox stones. PMID- 1887522 TI - Crystalluria determined by polarization microscopy. Technique and results in healthy control subjects and patients with idiopathic recurrent calcium urolithiasis classified in accordance with calciuria. AB - A retrospective study was done on the nature and degree of crystalluria in spontaneously voided fasting and postprandial urine of patients with recurrent idiopathic calcium urolithiasis (RCU) divided into normocalciuria (20 males, 20 females) and hypercalciuria patients (20 males, 20 females), and controls (20 males, 20 females). The crystals were obtained using a filter technique and identified by microscopy. In addition, individual data, clinical chemistry variables and indices reflecting the risk of calcium phosphate and calcium oxalate crystallization were evaluated. In contrast to findings of other investigators of crystalluria we observed only a few crystals on the filters. The most frequently occurring phases were (in this order) a urate-containing phase (tentatively termed uric), an amorphous calcium phosphate phase (tentatively termed isotropic) and a phase of spheroid-like particles, not yet definitely characterized (tentatively termed spheroid). Calcium oxalate crystals were found only exceptionally. There was no relationship between the degree of calciuria (normo- versus hypercalciuric RCU) and crystalluria. Among RCU, males generally had a predominance of the isotropic, females of the spheroid phase, as compared with controls. Also, RCU females were generally obese, and their spheroid score and lean body mass correlated negatively and significantly. The calcium phosphate and calcium oxalate risk indices were always low in normal individuals, higher in RCU. Patients of both sexes with urinary stones had normal parathyroid gland function, but higher total calcium in fasting serum and higher urinary pH as compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1887524 TI - Inhibition of calcium oxalate crystallization by urinary macromolecules. AB - The crystallization of calcium oxalate (CaOx) was determined in dialyzed urine samples collected between 0600 and 1000 hours from 18 normal men, 10 normal women and 13 men and 10 women with CaOx stone disease. Each urine samples was supersaturated by the addition of calcium chloride and sodium oxalate, and CaOx crystallization was followed by quantification of the [14C]-oxalate remaining in solution for 30 min after supersaturation of the sample. The rate of crystallization was compared with that in physiological saline. The surface area delimited by the urine and saline curves was used to express the inhibition of CaOx crystallization by urinary macromolecules (IUMM). The IUMM was significantly higher in urine from normal women than in that from stone-forming women (P less than 0.05), normal men (P less than 0.005), and stone-forming men (P less than 0.02). However, there were no significant differences between stone-forming men and stone-forming women, nor was IUMM higher in normal men than in stone-forming men. A high concentration of inhibitors might protect women from CaOx stone formation and be one factor explaining the lower stone-formation rate in women. Although low values were more predominate in normal men than in normal women, there were no significant differences between the groups when the inhibition was corrected for differences in urinary volumes. PMID- 1887525 TI - Studies of urease-induced crystallisation in undiluted human urine using the Coulter counter technique. AB - Urease-induced crystallisation was studied in different human urine samples after urease incubation. The studies were performed using the Coulter counter technique, which enables determination of the number and size of particles in a solution and calculation of the total particle volume. The crystallization took place in three consecutive but overlapping steps: (1) nucleation, (2) growth and (3) aggregation. The maximal number of particles obtained in the different samples varied little, but there was a great variation in particle size and total particle volume. The variation in particle size appeared to be mainly due to differences in particle growth, a factor that might be of importance for stone formation. PMID- 1887526 TI - Reduction in the anti-adherence activity of Tamm-Horsfall protein with increasing concentration of calcium. AB - Tamm-Horsfall glycoprotein (THP), at concentrations occurring in normal urine, was demonstrated to show anti-adherence activity for type-1 fimbriated Escherichia coli. Urine also showed anti-adherence activity, and urine from which the THP was precipitated showed a significant drop in activity. The addition of calcium to the incubation medium with THP, at concentrations normally found in the urine, had no effect on the anti-adherence activity of THP. However, concentrations of calcium higher than those normally occurring in the urine significantly decreased the anti-adherence activity of THP. It is suggested that individuals with above normal concentrations of calcium in the urine may be at increased risk for urinary tract infections since the protective effect of THP is compromised. PMID- 1887527 TI - Crystalluria in marathon runners. III. Stone-forming subjects. AB - In order to investigate further the possible relationship between urinary stone formation and marathon running, the crystalluria in seven male, stone forming runners was characterized. Particle size distribution curves (Coulter counter) and crystal number, size and morphology (scanning electron microscopy) were measured. These studies suggest that urinary stone formation may be accelerated in those subjects with previous histories of renal stone formation but that the nature of the crystalluria is favourably affected by an increase in fluid intake. The presence of large quantities of mucoid material in the urine of "natural" stone formers and its absence in the urine of stone-forming runners is cited as evidence for the existence of different aetiological mechanisms in these groups. It is concluded that while natural stone formers may be at chronic risk of stone formation due to pathological factors, marathon runners may be at acute risk due to factors associated with long distance running itself. PMID- 1887528 TI - Reduction of calcium excretion in the stone-forming kidney in unilateral ureteral obstruction. AB - Thirteen urolithiasis patients with unilateral obstructive uropathy were treated with percutaneous nephrostomy (PCN) either for urinary diversion, endopyelotomy, nephrolithtotmy or chemolysis. After percutaneous nephrostomy, the individual urine volume, creatinine clearance (Ccr), urinary absolute and fractional excretions of sodium, potassium, calcium, magnesium and inorganic phosphate were measured separately in timed urine collections from a pigtail catheter and from the urethra. The data showed that Ccr and the absolute urinary excretions of sodium, potassium, calcium, magnesium and inorganic phosphate were significantly lower in the PCN kidney immediately or 2 days after relief of obstruction. The ratio of total urinary calcium excretion to urinary creatinine excretion in the obstructed kidney was significantly greater than that in the contralateral kidney. The fractional excretions of calcium and magnesium increased as renal function decreased. The results showed that when the total Ccr is below normal, the apparent excretion of urinary calcium will be underestimated. However, when the total Ccr of patients is within normal range, hypercalciuria may be detected adequately and thus favors early implementation of an appropriate therapeutic strategy. PMID- 1887529 TI - Investigations of the efficacy of ascorbic acid therapy in cystinuria. AB - We investigated ascorbic acid therapy for cystinuria in a study of seven healthy control persons and seven cystinuric patients. The study lasted 9 days. During the first period, we collected 24-h urine specimens from all subjects on 3 consecutive days. Starting on day 4, all were given 5 g ascorbic acid/day for a period of 6 days. On the last 3 days, 24-h urine specimens were again collected. Quantitative amino acid determination was performed using an HPLC method described elsewhere. During ingestion of ascorbic acid, the mean excretion of cysteine by the control group increased from 134.1 to 159 mumol/day, whereas the excretion of cystine decreased from 107.1 to 82 mumol/day. The corresponding values for the cystinuric patients increased from 352.4 to 452.1 mumol/day for cysteine and decreased from 4,131.6 to 3,663.2 mumol/day for cystine. Thus, ascorbic acid seems to have only mild reducing properties in respect to cystine. PMID- 1887530 TI - Chronobiology of urinary citrate excretion amongst stone-formers and healthy males from north western India. AB - Urinary citrate excretion was estimated colorimetrically from urine samples collected every 3 h for 24 h from 25 healthy adult males (non-stone formers; mean age 39 +/- 7 years) and 25 male patients suffering from calcium nephrolithiasis (stone formers; mean age 41 +/- 6 years). The 24 h citrate excretion was 2.47 +/- 0.65 mmol in non-stone formers and 2.02 +/- 0.71 mmol in stone formers. This difference was not significant. However, cosinor rhythmometry revealed a significant circadian rhythmicity in urinary citrate excretion in the healthy males which was absent in the stone formers; the amplitude was 0.06 mmol in non stone formers and 0.017 mmol in stone formers. The acrophase was located at 14:25 h in non-stone formers and at 23:30 h in stone formers. PMID- 1887531 TI - The case for relief of ureteropelvic junction obstruction in neonates and young children at time of diagnosis. PMID- 1887532 TI - Transurethral resection of prostate prior to definitive irradiation for prostate cancer. Lack of correlation with treatment outcome. AB - From 1970 through 1983, 107 patients with newly diagnosed adenocarcinoma of the prostate were treated with radiotherapy with curative intent at Duke University Medical Center. Forty-five patients (42%) underwent transurethral resection of the prostate (TURP) for diagnostic and/or therapeutic purposes prior to beginning radiotherapy. Sixty-one patients (57%) were diagnosed by needle biopsy. TURP and needle biopsy groups were comparable (age, elevated acid phosphatase, early [A2, B] and late [C, D1] disease stages, and follow-up). TURP patients were more likely to have poorly differentiated tumors and were more often given concurrent hormonal therapy. Both univariate and multivariate analyses to study the effect of TURP on patients with prostate cancer treated with radiotherapy were done. We were unable to demonstrate any adverse impact of TURP on the outcome of radiation therapy for prostate cancer. This issue remains controversial and should be addressed in a prospective, randomized trial. PMID- 1887533 TI - Pathologic review of consecutive radical prostatectomy specimens. Nerve sparing versus nonnerve sparing. AB - Retrospective pathologic analysis was conducted of specimens from 88 radical retropubic prostatectomy operations performed between 1982 and 1987 inclusive. The median age of patients was sixty years (range, 46 to 73 years). Of the 88 radical prostatectomies performed, 51 were nerve-sparing (40 bilateral) and 37 were nonnerve-sparing (11 unilateral) procedures. Preoperative clinical staging was similar in both groups. Thirty-five of 37 patients (95%) in nonnerve-staging group and 51 of 51 patients (100%) in nerve-sparing group had clinical Stage B2 disease or less. Pathologic staging in both groups was also similar. In 26 of 37 patients (70%) in nonnerve-sparing group and in 35 of 51 patients (69%) in nerve sparing group, disease remained localized to the prostate. Both groups were analyzed retrospectively to determine whether or not the incidences of microinvasion of capsule and of extraprostatic disease differed. Review of the apical and lateral margins of the specimens revealed no statistically significant difference in either the degree of microinvasion of capsule or the incidence of extraprostatic disease between the groups. PMID- 1887534 TI - Value of serum alkaline phosphatase and radionuclide bone scans in patients with renal cell carcinoma. AB - Ninety-one patients who underwent radical nephrectomy for renal cell carcinoma (RCC) were reviewed to determine the prognostic value of serum alkaline phosphatase (SAP) levels and radionuclide bone scan. A preoperative SAP greater than 127 IU/L was a strong indicator of eventual disease progression or death, and an elevated SAP was a better predictor of eventual outcome than bone scan. PMID- 1887535 TI - Primary adenocarcinoma of bladder. AB - Between April 1983 and December 1987, we have treated and followed 16 patients at the University of Southern California for adenocarcinoma of the bladder. In 10 patients, the cancer originated from a nonurachal source; all underwent radical cystectomy, bilateral pelvic lymph node dissection, and urinary diversion. The other 6 patients had an apparent urachal origin of their cancer. Half of these patients were treated with radical cystectomy and urinary diversion and half were treated initially with segmental cystectomy. Presenting characteristics (age, sex ratio, and symptoms) were similar for both groups. Three-year adjusted acturial tumor-free survival rates for the two groups were 48 percent and 31 percent, respectively. We advocate an aggressive approach of radical cystectomy, bilateral pelvic lymph node dissection, and urinary diversion for all invasive adenocarcinoma of the bladder, regardless of location. PMID- 1887536 TI - Cigarette smoking and other vascular risk factors in vasculogenic impotence. AB - A total of 132 consecutive patients with erectile impotence underwent extensive evaluation, including vascular evaluation with intracavernous injection of papaverine and penile duplex ultrasonography, to determine the etiology of impotence. Three vascular risk factors, smoking, diabetes mellitus and hypertension, were investigated for their impact on vasculogenic impotence. The patients were divided into four groups: one with no risk factors, one with one vascular risk factor, one with two vascular risk factors, and one with all three risk factors. The results of penile vascular evaluation in these patient groups were compared. The incidence of penile vascular impairment was found to be higher in patients with one vascular risk factor than in those with none. The proportion of abnormal penile vascular findings significantly increased as the number of risk factors increased. These data confirm the important role of vascular risk factors, smoking, diabetes mellitus, and hypertension, in the pathogenesis of organic impotence. PMID- 1887537 TI - Percutaneous nephrolithotomy in transplanted kidney. AB - Renal transplant patients with urologic complications can be managed safely with percutaneous techniques. The development of renal calculi in transplanted kidneys is uncommon, but in these cases complications such as infection and urinary tract obstruction with impairment of graft function can occur. We report 2 cases managed successfully with percutaneous nephrolithotomy. PMID- 1887538 TI - Bilateral renal hemangiopericytoma. AB - The first reported case of bilateral renal hemangiopericytoma is presented. The 19 previous renal hemangiopericytomas that have been reported in the world literature are reviewed. This lesion has afflicted patients ranging in age from sixteen to sixty-eight years (mean 41 years) with an equal sex distribution. Mortality from hemangiopericytoma of the kidney has been 50 percent, and the primary mode of therapy remains surgical. PMID- 1887539 TI - Foley and Hutchins needle equal Councill catheter. PMID- 1887540 TI - Leiomyosarcoma of renal vein. AB - Leiomyosarcomas arising from the renal vein are rare tumors: only 13 cases are found in the literature. We report a case in a sixty-one-year-old woman who presented with back pain and hematuria. She underwent resection of the tumor and an ipsilateral nephrectomy. The tumor recurred locally, and the patient died thirty months after diagnosis. Review of the cases reported in the literature reveals the aggressive nature of these tumors and the need for a combined therapeutic approach. PMID- 1887541 TI - Retroperitoneal fibrosis as host response to papillary renal cell carcinoma. AB - A case of papillary renal cell carcinoma associated with retroperitoneal fibrosis is described. This type of fibrosis has not been previously reported to be associated with renal cell carcinoma. The case is of additional interest in that it implicates an immune phenomenon in the pathogenesis of the fibrosis, involving both putative tumor antigens and antigens associated with tumor growth but unrelated to tumor cells. PMID- 1887542 TI - Role of lymphangiography in staging testicular seminoma. AB - Bipedal lymphangiography (LAG) and abdominal/pelvic computerized tomography (CT) are both useful in evaluating retroperitoneal lymph nodes in early-stage testicular seminoma. Fifty-four patients who had both radiologic studies performed between 1982 and 1986 were identified, and their films were reviewed. Four patients had evidence of retroperitoneal lymph node metastases on both CT and LAG. Of the 50 patients who had normal findings on CT scan, 39 (78%) had a normal LAG and 11 (22%) had a positive LAG. All 11 patients had architectural abnormalities within normal-sized nodes. No patient had positive findings on CT with negative LAG. In addition to aiding in staging, LAG is very useful in designing radiation treatment portals. Therefore, we believe that LAG can continue to play an important role in the accurate staging and treatment of patients with testicular seminoma. PMID- 1887543 TI - Multicenter study of superficial bladder cancer treated with intravesical bacillus Calmette-Guerin or adriamycin. Results of long-term follow-up. AB - We evaluated 158 cases of patients with superficial bladder cancers (Stages Ta, T1, and Tis). These cases were treated with either intravesical bacillus Calmette Guerin (BCG) (Tice strain) or Adriamycin (ADR), in a multicenter, nonrandomized study. One hundred thirty-one of these patients were followed up; the results continue to show a higher percentage of initial complete remissions with BCG (68%) than with ADR (57%). With additional therapy, both BCG and ADR achieved complete remission in 83 percent of the patients. When 7 failures with patients taking ADR were switched to BCG and the disease cleared, the rate of complete remission for BCG rose to 85 percent. The recurrence rate per 100 patient-months was only slightly different for BCG (0.9) and ADR (0.8). The percentage of progressions continued to be higher for BCG (8%) than for ADR (5%). Cystectomies were performed in 2.5 percent of the BCG patients. Using the Cox regression model with covariates, we found drug treatment, tumor grade, and sex to be statistically significant in determining failures throughout the protocol. Although both BCG and ADR were effective over the course of the study, BCG is the drug of choice for residual tumor (Stages T1 and Tis). PMID- 1887544 TI - Multielement analysis of kidney tissue with renal calculi. AB - Tissue distribution and concentration gradients of macro- and micro-elements in the papilla, medulla, and cortex of human kidney with renal calculi were measured with spectrometer. An uninvolved portion of the hypernephroma kidney was used as control. Cadmium (Cd), cobalt (Co), and molybdenum (Mo) were least in amount in renal papilla as compared with the cortex and medulla in renal stone kidney. Overall there was less Mo in stone kidney tissue, and also significantly less when compared with that of control renal papilla. Considering the reported fact that Mo was found in high concentrations in urinary tract stones and our data that Mo was less in stone kidney, it is speculated that Mo may play some unexplained but significant role in certain stage(s) of the stone formation. PMID- 1887545 TI - Conservative management of stress urinary incontinence. PMID- 1887546 TI - Psychologic factors affect erectile response to papaverine. PMID- 1887547 TI - Resection of the distal interphalangeal joint in cattle: an alternative to amputation. AB - A technique for the resection of the distal interphalangeal joint of cattle with infectious arthritis of the joint is described. The procedure has advantages over amputation of the digit because a weight-bearing claw is retained so that the animal can move on slatted floors and at pasture, and its productive life can be extended. PMID- 1887548 TI - Selenium and vitamin E in blood sera of cows from farms with increased incidence of disease. AB - Selenium and vitamin E concentrations were measured in the blood sera of 287 cows in 91 herds. Herds with chronic mastitis and muscle diseases had significantly lower selenium concentrations (10.4 +/- 5.26 and 11.7 +/- 8.63 micrograms/litre serum, respectively) than healthy control herds (17.7 +/- 15.00 micrograms/litre). The selenium concentrations in herds with low fertility did not differ from control herds. The vitamin E concentrations were similar in all the herds. Supplementation of the mineral mixture with 20 mg sodium selenite and 2 g vitamin E/kg on 15 farms with a deficient selenium supply increased the selenium concentrations in the blood within two months in 12 of the herds. The vitamin E concentrations were hardly influenced by the supplementation. PMID- 1887550 TI - Control of fighting dogs. PMID- 1887549 TI - Bovine leptospirosis in cattle in Portugal: bacteriological and serological findings. PMID- 1887551 TI - Use of enrofloxacin in laying birds. PMID- 1887552 TI - Ear mites in sheep. PMID- 1887554 TI - Dangerous Dogs Bill rushed through the Commons. PMID- 1887553 TI - Separation distress. PMID- 1887555 TI - Cattle veterinarians examine alternative therapies. PMID- 1887556 TI - Pharmacokinetics and pharmacodynamics of piroxicam in dogs. AB - Piroxicam was administered to beagle dogs intravenously and orally at a dose rate of 0.3 mg/kg bodyweight. It had an elimination half-life of 40.2 hours, a volume of distribution of 0.29 +/- 0.02 litres/kg and a body clearance rate of 0.066 litres/hour. When administered orally it was 100 per cent bioavailable and maximum plasma concentrations were achieved quickly (3.1 +/- 1.0 hours). Piroxicam inhibited the generation of thromboxane B2 in the blood of dogs by more than 70 per cent and more than 50 per cent inhibition was maintained in most animals for 48 hours. PMID- 1887557 TI - Effects of four hormone treatments after calving on uterine and cervical involution and ovarian activity in cows. AB - Uterine and cervical involution after calving was measured sequentially in 25 parous commercial Friesian cows by using electronic calipers and real-time ultrasound imaging, transrectally. Ovarian activity was monitored by using real time ultrasound imaging and by the assay of milk progesterone concentrations. Peripheral plasma prostaglandin F2 alpha metabolite concentrations were assayed during this period. Five groups of five cows were treated intramuscularly, approximately 48 hours after calving, with either 100 mg progesterone in oil, 25 mg dinoprost tromethamine, 5 mg oestradiol benzoate, 1.2 mg of the long-acting oxytocin analogue carbetocin or 5 ml sterile water. There were no statistically significant differences between the intervals from calving to the completion of involution or between the intervals from calving to the first ovulation for the cows in the different groups. The mean PGFM concentrations in the peripheral circulation were significantly higher in the carbetocin-treated group, presumably owing to the stimulation of endogenous prostaglandin F2 alpha secretion. This study provides no evidence that a single treatment with any of the four hormones significantly affected the reproductive function of the cows after calving. PMID- 1887558 TI - Surgical repair of a cranial meningocele in a calf. AB - A meningocele at the anterior fontanelle was diagnosed in a two-and-a-half month old Meuse-Rhine-Yssel calf. After radiographic and ultrasonographic evaluation, the meningocele was successfully repaired surgically. PMID- 1887559 TI - Necrotic enteritis in suckled calves. PMID- 1887560 TI - Wing tip oedema and dry gangrene of raptors. PMID- 1887561 TI - Calf diarrhoea quiz. PMID- 1887562 TI - Gastrointestinal disorders. PMID- 1887563 TI - Nematodirus species on St Kilda. PMID- 1887564 TI - A mathematical model for Mycobacterium bovis excretion from tuberculous cattle. AB - An analysis was carried out of available information from a series of experiments on the excretion of M. bovis from infected cattle. The analysis indicated that an inverse exponential relationship exists between 'dose' of organisms given and the delay before excretion commences. This relationship was represented mathematically. Available field data supported the relationship and indicated that in natural bovine tuberculosis excretion of M. bovis begins around 87 days after infection occurs. It is also suggested that the data supports the concept of single nuclei infections in cattle. PMID- 1887565 TI - Experimental reproduction of respiratory tract disease with bovine respiratory syncytial virus. AB - An experiment was conducted to reproduce respiratory tract disease with bovine respiratory syncytial virus (BRSV) in one-month-old, colostrum-fed calves. The hypothesized role of viral hypersensitivity and persistent infection in the pathogenesis of BRSV pneumonia was also investigated. For BRSV inoculation a field isolate of BRSV, at the fifth passage level in cell culture, was administered by a combined respiratory tract route (intranasal and intratracheal) for four consecutive days. Four groups of calves were utilized as follows: Group I, 6 calves sham inoculated with uninfected tissue culture fluid and necropsied 21 days after the last inoculation; Group II, 6 calves inoculated with BRSV and necropsied at the time of maximal clinical response (4-6 days after the last inoculation); Group III, 6 calves inoculated with BRSV and necropsied at 21 days after the last inoculation; Group IV, 6 calves inoculated with BRSV, rechallenged with BRSV 10 days after initial exposure, and necropsied at 21 days after the initial inoculation. Clinical response was evaluated by daily monitoring of body temperature, heart rate, respiratory rate, arterial blood gas tensions, hematocrit, total protein, white blood cell count, and fibrinogen. Calves were necropsied and pulmonary surface lesions were quantitated by computer digitization. Viral pneumonia was reporduced in each principal group. Lesions were most extensive in Group II. Disease was not apparent in Group I (controls). Significant differences (p less than 0.05) in body temperature, heart rate, respiratory rate, arterial oxygen tension, and pneumonic surface area were demonstrated between control and infected calves. Results indicate that severe disease and lesions can be induced by BRSV in one-month-old calves that were colostrum-fed and seropositive to BRSV. BRSV rechallenge had minimal effect on disease progression. Based on clinical and pathological response, results did not support viral hypersensitivity or persistent infection as pathogenetic mechanisms of BRSV pneumonia. PMID- 1887566 TI - Immunological properties of Actinobacillus pleuropneumoniae hemolysin I. AB - The 105 kDa hemolysin I protein from Actinobacillus pleuropneumoniae serotype I type strain 4074 (HlyI) was shown by immunoblot analysis to be the predominant immunogenic protein if convalescent field sera or sera from pigs experimentally infected with A. pleuropneumoniae serotype 1 were used. SDS gel- and immunoblot analysis using total culture, washed cells or culture supernatant showed that HlyI is essentially secreted and is not found attached to the bacteria. Proteins in the 105 kDa range that react strongly with anti-HlyI antibody, are produced by all serotypes and are presumed to be their hemolysins. Sera from pigs experimentally infected with each of the 12 serotypes strongly reacted with HlyI. In addition, some sera from pigs that were confirmed to be negative for A. pleuropneumoniae, also reacted with HlyI as well as with related proteins from Actinobacillus rossii and Actinobacillus suis. These two species produce proteins in the 105 kDa range which cross-react strongly with HlyI. They could be the source of the immunological reactions of the A. pleuropneumoniae-negative sera with HlyI. However, no cross-reactions could be found between HlyI and the Pasteurella haemolytica leukotoxin, the Escherichia coli alpha-hemolysin or related proteins from various hemolytic E. coli strains isolated from pigs. The immunological cross-reactions of HlyI with related proteins from A. rossii, A. suis and possibly from other bacterial species may create uncertainty in interpretation if HlyI is used as the antigen in serodiagnosis of A. pleuropneumoniae. PMID- 1887567 TI - Relationship between the iron regulated outer membrane proteins and the outer membrane proteins of in vivo grown Pasteurella multocida. AB - The SDS-PAGE patterns of the outer membrane protein (OMP) extracts of Pasteurella multocida strain P1059, grown under iron-restricted, iron-replete and in vivo conditions, were examined. The results showed that the iron-regulated outer membrane proteins (IROMPs) with molecular masses of 76 kDa, 84 kDa, and 94 kDa were expressed by bacteria grown in iron-restricted media. They were also expressed by in vivo grown P. multocida. Convalescent-phase sera, obtained from turkeys which had survived pasteurellosis, contained antibodies that reacted intensly with th three IROMPs. This indicated that these proteins were expressed in vivo. Bacteria expressing the IROMPs showed greater binding to Congo Red when compared to cells not expressing IROMPs. Cells expressing the IROMPs or its OMP extracts grown in iron-restricted media also showed greater binding to 59Fe pasteurella siderophore (multocidin) when compared to bacteria or its extracts not expressing IROMPs. Convalescent-phase sera, which contained antibodies against the IROMPs, blocked this specific 59Fe-multocidin binding to IROMPs. Autoradiography was used to determine which of these IROMPs functioned as a receptor for the iron-multocidin complex. The results suggested that these three IROMPs have specific epitopes for binding to the iron multocidin complex. PMID- 1887568 TI - Evaluation of a toxoid for protection of rabbits against enterotoxaemia experimentally induced by trypsin-activated supernatant of Clostridium spiroforme. AB - Investigations were conducted into an enterotoxaemia caused by Clostridium spiroforme responsible for significant losses in commercial rabbit farms in Western Australia. Two trials using laboratory and farm bred rabbits were performed to evaluate the protective value of a toxoid prepared from the supernatant of C. spiroforme cultures against intraperitoneal challenge with the trypsin-activated toxin of C. spiroforme. The trials showed clearly that a single vaccination at weaning (four weeks) was protective against toxin but more complete and lasting protection was conferred following a second vaccination administered 14 days after the first. Adults likewise showed similar levels of protective antibodies but did not appear to pass on this protection to their kits although ELISA results indicated levels of antibody in kits from unvaccinated mother to be lower than progeny from vaccinated mothers. However antibody levels in kits from vaccinated mothers were very low and did not protect against challenge with toxin. PMID- 1887569 TI - [Angiocardiographic diagnosis of the position of the interventricular septal defect in a case of double outlet of the great vessels from the right ventricle]. AB - The paper is devoted to analysis of the results of angiocardiographic investigation of 237 patients with a double deflection of great vessels (DDGV) from the right ventricle (RV) (the patients ranged in age from 3 months to 23.5 years) to study the potentialities of the method in the diagnosis of a defect position of the interventricular septum (DIVS). Angiographic investigation permitted a sufficiently accurate determination of a DIVS position in DDGV from the RV. Of paramount importance for determining a DIVS position is the establishment of the interrelationships of the latter with the infundibular septum and the openings of major arteries. For diagnosis of a DIVS position one should necessarily use left and right ventriculography both in standard and axial projections. PMID- 1887570 TI - [Diagnosis of restenosis of the coronary artery following x-ray endovascular dilatation]. AB - Altogether 40 patients with stable angina of effort were investigated in a long term period after roentgenovascular dilatation of one or two coronary arteries. Control coronography was performed in 22 patients with lowered exercise tolerance. A reliable feature in the development of hemodynamically significant restenosis and/or "new" coronary stenosis in 11 patients was a combination of average and low exercise tolerance with its negative dynamics. For patients with I functional class, a sign of restenosis and/or "new" stenosis was the appearance of the ischemic shift of the CT-segment on ECG during bicycle testing. An efficient selection of patients resulted in increased sensitivity and specificity of noninvasive tests. PMID- 1887571 TI - [The effect of contrast ventriculography of the left ventricle on intracardiac hemodynamics in patients with ischemic heart disease]. AB - The effect of left ventricular (LV) contrast ventriculography (VG) on the state of intracardiac hemodynamics during the administration of a contrast medium and 30-40 sec. after it was investigated in 48 CHD patients. It followed retrograde catheterization of the left ventricle by a parallel use of two catheters that permitted recording intraventricular pressure directly during LV VG. The performance of left VG with 76% urografin administered in a dose of 0.6-0.8 ml/kg with the rate of 13-15 ml/s produced no significant change in the state of intracardiac hemodynamics, relaxation and pumping function of the LV in the course of the first three contrasted cardiocycles. Transitory disorder of hemodynamics observed in the patients after contrast VG was restored by itself in 15-20 min. PMID- 1887572 TI - [X-ray endovascular dilatation using an axillary access]. AB - Based on the analysis of 39 observed cases, the authors consider various aspects of the use of roentgenovascular dilatation by an axillary access: problems of methods, indications and contraindications; they also assess the advantages and shortcomings of the access. PMID- 1887573 TI - [The tolerance to different x-ray contrast preparations used in coronary angiography in patients with acute myocardial infarction]. AB - Coronary angiography (CAG) was performed in the acute period of myocardial infarction in 41 patients using verografin and in 38 patients using omnipack. In a high risk of CAG performance the tolerance of omnipack was better than that of verografin. Omnipack causes allergic reactions less frequently, disturbs less nitrogen excretory function of the kidneys and myocardial bioelectric activity. PMID- 1887574 TI - [X-ray diagnosis of a small quantity of liquid in the pericardial cavity]. AB - X-ray symptomatology of small pericardial effusions was studied on the basis of analysis of clinicoroentgenological and echocardiographic investigation of 173 patients with various chest diseases. Comparison of x-ray and USI results led to a conclusion of the effectiveness of polypositional roentgenography for the detection of small amounts of fluid in the pericardial cavity. PMID- 1887575 TI - [Computed tomography in cancer of the colon]. PMID- 1887576 TI - [The use of bone transplants in total prosthesis of the hip joint (preliminary results of magnetic resonance tomography)]. PMID- 1887577 TI - [Continuity and succession in pre- and postgraduate studies in radiodiagnosis]. PMID- 1887578 TI - [The roentgenologist as therapist]. PMID- 1887580 TI - [Comments on the article by V.B. Antonovich and L.B. Kirichenko "Clinico roentgeno-endoscopic and morphologic (morphometric) correlations in chronic non ulcerative colitis"]. PMID- 1887581 TI - [Current outlook on improving the detection of stomach cancer (review of the literature)]. PMID- 1887582 TI - [Radiologic diagnosis in 1989 (an analytic review of publications in Soviet medical journals)]. PMID- 1887583 TI - [A case of a female patient with hepatic and splenic hemangiomatosis: interventional radiologic and surgical interventions]. PMID- 1887584 TI - [Arterial occlusion by the organosilicon composition Embosil and its components]. PMID- 1887585 TI - [A device for fixing the electro-roentgenographic image]. PMID- 1887586 TI - Identification of endoprotease activity in the trans Golgi membranes of rat liver cells that specifically processes in vitro the fusion glycoprotein precursor of virulent Newcastle disease virus. AB - A ubiquitous host endoprotease(s) responsible for activation of the fusion glycoprotein precursor (F0) of virulent Newcastle disease virus (NDV) is an important determinant for its spreading and organ tropism in the host. To characterize the virus-activating protease (VAP), we isolated endoprotease activity from the trans Golgi membranes of rat liver cells by using F0-containing NDV particles grown in a lymphoid cell line NALM6 as substrate. The enzyme cleaved in vitro only the F0 protein of virulent NDV but not that of an avirulent strain, suggesting that it specifically recognizes pairs of basic residues at the cleavage site. Furthermore, the enzyme was found to be membrane-bound, calcium ion-dependent, and active over a broad pH range, from 6 to 8. The inhibitor spectrum of the protease together with the enzyme properties described above indicates that it is a KEX2-like enzyme. Experiments using monensin, A23187, and chloroquine indicate that the F0 cleavage of virulent NDV occurs normally in rat primary hepatocytes at or before the trans Golgi and is a calcium-dependent process. The correspondence between the characteristics of the cleavage in rat hepatocytes and those of the rat protease in vitro indicates that the endoprotease is a strong candidate for the VAP that determines the pantropic nature of virulent NDV. PMID- 1887587 TI - Coliphage Q beta RNA replication: RNA catalytic for single-strand release. AB - We have generated 14 recombinant RNA templates for Q beta replicase, each having either an exogenous inverted repeat sequence or a sequence with no repeat. These templates were used to initiate in vitro replication by Q beta replicase in amounts that saturated the enzyme. We observed that replication rates for RNAs that putatively contained secondary structures in the recombinant sequences ranged from 33 to 69% that of a wild-type MDV-1 RNA control, regardless of the size of the inserted hairpin. Moreover, most of the newly synthesized RNA was present as single strands. Alternatively, RNAs that contained exogenous sequences not expected to form secondary structures exhibited replication rates less than 25% that of MDV-1. In each case, the reaction rate was correlated with the length of the insertion, and the majority of product RNA consisted of duplexed molecules (complementary plus and minus strands hybridized together). When these same recombinant RNAs were used in reactions in which the molar amount of RNA template was 10(6)-10(7) times lower than that of the replicase, only those that putatively contained secondary structures survived in the replication reaction. Our results are consistent with the theory that hairpin structure formation during RNA synthesis by Q beta replicase directly influences the regeneration of single-stranded RNA products. PMID- 1887588 TI - An L (polymerase)-deficient rabies virus defective interfering particle RNA is replicated and transcribed by heterologous helper virus L proteins. AB - A rabies virus-derived defective interfering particle (DI) was isolated and characterized. The DI genome contained an internal deletion of 6.4 kb spanning the 3' moiety of the pseudogene region (psi) and most of the L gene. DI-specific monocistronic N, NS, and M mRNAs as well as a G/L fusion mRNA were transcribed in cells coinfected with DI and helper virus. In addition, polycistronic DI RNAs and standard virus RNAs with internal A stretches and intergenic regions were found. Superinfection experiments showed that heterologous rabies-related viruses (Lyssavirus serotypes 2, 3, and 4) can complement the L deficiency of the DI genome. The heterologous polymerase proteins recognize correctly the replicational and transcriptional signal sequences of the Lyssavirus serotype 1 derived DI. PMID- 1887589 TI - Genomic and subgenomic RNAs of rabbit hemorrhagic disease virus are both protein linked and packaged into particles. AB - The major subgenomic RNA of the calicivirus rabbit hemorrhagic disease virus which codes for the viral capsid protein has been cloned as cDNA. The nucleotide sequence of this mRNA was shown to be identical to the 3' terminal region of the genomic RNA. The 5' end of the mRNA corresponds to position 5296 of the genomic sequence; except for two differences the first 16 nucleotides of genomic and subgenomic RNAs are identical. After isolation from liver tissue viral genomic and subgenomic RNAs were found to be resistant to RNase degradation. This protection was due to RNA packaging into particles. Sucrose density gradient centrifugation of liver homogenates allowed separation of such particles containing either genomic RNA or subgenomic RNA. Genomic and subgenomic RNAs are protein-linked and for the genomic molecule this interaction is localized within the first 179 nucleotides. After radioactive labeling of purified RNA and subsequent RNase treatment a protein of 15 kDa was identified. PMID- 1887590 TI - Oligomerization and transport of the envelope protein of Moloney murine leukemia virus-TB and of ts1, a neurovirulent temperature-sensitive mutant of MoMuLV-TB. AB - Ts1, a temperature-sensitive mutant of Moloney murine leukemia virus-TB (MoMuLV TB), causes a progressive hindlimb paralytic disease in susceptible strains of mice. Previously, it has been shown that a single amino acid substitution, Val-25 ---Ile in gPr80env, is responsible for the temperature sensitivity, inefficient transport, and processing of gPr80env at the restrictive temperature and the neurovirulence of ts1. Since the neurovirulence of ts1 is associated with inefficient transport and processing of gPr80env and since in other systems involving viral envelope proteins it has been shown that correct folding and oligomerization of envelope monomers are required for efficient transport, we have investigated the ability of gPr80env derived from either wild-type MoMuLV-TB or ts1 to associate into oligomeric complexes. In these experiments, we establish that at both the restrictive and the nonrestrictive temperatures gPr80env molecules derived from MoMuLV-TB associate to form oligomeric complexes and these oligomers are most likely trimers. gPr80env molecules derived from ts1 also oligomerize at both temperatures; however, at the restrictive temperature, most of the molecules within the trimeric complexes remain as gPr80env and are not processed to gp70 and Prp15E. These results indicate that lack of oligomerization of gPr80env is not responsible for the transport defect of ts1. Therefore, by interacting specifically with critical sites within target cells, oligomers of mutant gPr80env rather than "tangles" of monomeric viral envelope proteins may be involved in the neurodegenerative disorder produced by ts1. PMID- 1887591 TI - Human immunodeficiency virus infection elicits early antibody not detected by standard tests: implications for diagnostics and viral immunology. AB - The FDA-approved tests for diagnosis of HIV exposure depend on detection of specific antibody in serum. HIV infection is missed in some individuals because they score seronegative by the standard clinical EIA and Western blot assays. This apparent immunological "silent" period following infection may last for months and has been reported to be as long as 3 years in rare cases. Is there truly a lack of an immune response or is there a more subtle, narrowly focused antibody response in these HIV-infected individuals which is not detected by the current tests? Using a nondenaturing serological assay (immunofluorescence of live infected T-cells), we found that each of four infected individuals "seronegative" by the standard tests did possess antibody against native HIV proteins expressed on infected cells. These antibodies reacting with native HIV antigenic epitopes were of the IgG isotype, they cross-reacted with many, but not all, of seven random HIV-1 isolates, and one of the sera immunoprecipitated HIV gp160 from NP-40-solubilized infected cells. These results show that seronegative, high-risk, infected individuals can actually be seropositive and that different types of assays using native antigenic epitopes may be required for screening. Implementation of these findings thus may decrease HIV transmission. These results also highlight the importance of protein conformation for many natural viral antigenic epitopes. PMID- 1887592 TI - Mutational analysis of the putative catalytic triad of the cowpea mosaic virus 24K protease. AB - To investigate the mechanism of action of the cowpea mosaic virus (CPMV) 24K protease, a full-length cDNA clone of bottom component (B) RNA has been constructed from which RNA can be transcribed in vitro using T7 RNA polymerase. Translation of the resulting RNA in rabbit reticulocyte lysate leads to the synthesis of a 200 kDa product (the 200K protein) which cleaves itself in a manner identical to that of the product translated from B RNA isolated from virions. Site-directed mutagenesis of the full-length clone was used to examine the effects of altering individual amino acids in the 24K protease on its activity. The results obtained are consistent with the prediction that the 24K protease is structurally similar to the trypsin-like family of serine proteases and suggest that His40, Glu76, and Cys166 comprise the active site. Substitution of Cys166 by a serine residue results in an enzyme with reduced catalytic activity. PMID- 1887593 TI - Trimerization of the reovirus cell attachment protein (sigma 1) induces conformational changes in sigma 1 necessary for its cell-binding function. AB - The implications of reovirus sigma l protein trimerization on its cell-binding function were investigated. Both monomeric and trimeric forms of sigma l were found to be present when full-length type 3 reovirus Sl transcripts prepared in vitro were translated in rabbit reticulocyte lysates. Pulse-chase experiments demonstrated that monomers were precursors of trimers. However, only the trimeric form was capable of binding to cell surface receptors. Protease and antibody recognition analyses revealed significant structural differences between these two sigma l forms at both the N- and C-termini. Our results suggest that trimerization of protein sigma l is accompanied by extensive conformational changes necessary for its cell attachment function. PMID- 1887594 TI - Insecticidal effects of an insect-specific neurotoxin expressed by a recombinant baculovirus. AB - The scorpion Androctonus australis has a peptide (AaIT) which selectively targets the insect sodium channel. This mode of action is similar to that of many widely used chemical insecticides. When Bombyx mori larvae were infected with a recombinant baculovirus carrying a synthetic AaIT gene, the expressed protein was secreted into the hemolymph and caused symptoms consistent with sodium channel blocking, including tremors and feeding cessation at 40 hr p.i. followed by paralysis and death by 60 hr p.i. Larvae infected with control virus died by 96 hr p.i. These results indicate that foreign genes can be used in recombinant baculoviruses to reduce insect feeding damage and increase the rate of insect kill. PMID- 1887595 TI - DNA replication of wheat dwarf virus, a geminivirus, requires two cis-acting signals. AB - Replication of the single-stranded DNA genome of wheat dwarf virus (WDV) leads to the accumulation of covalently closed double-stranded DNA of genome length in infected cells. By studying the replication properties of a naturally occurring deletion mutant of WDV isolated from infected plants and of deletion mutants constructed in vitro, we have defined cis-acting regions required for viral DNA replication. The results show that two distinct regions are required in cis to yield the normal replicative forms of WDV-DNA. PMID- 1887596 TI - [The integration of the current problems of disaster medicine into the postgraduate training of military physician administrators]. PMID- 1887597 TI - [Let us raise the prestige of the profession of military physician]. PMID- 1887598 TI - [The current problems in the postgraduate training of military physicians]. AB - The existing medical intern-structures of Military Districts and Fleets cannot meet modern requirements on post-graduate training of military physicians because of its restricted possibilities. It is proposed to reform these structures in the regional Military Medical Institutes (each institute in the interests of several Military Districts or Fleets) for advanced training of physicians. The further improvement of the military physicians' qualification will require new forms and methods of training. It's necessary to increase the efficiency and quality of current and long-term planning of the training process by a wide application of computers. It is reasonable to conduct proficiency test cycles, which will directly influence upon further transfer or/and medical classification estimate of the physician. The training must be performed concerning the principle "work and-study". The goals of training must converge towards further medical activities, and the final results of studies must provide for thorough professional skill of the physician. It is advisable to apply more widely the active methods of training, such as practical and clinic games, methods of concrete situation analysis, etc. PMID- 1887599 TI - [The principles and organization of the medical support for the defensive regiment (2)]. PMID- 1887600 TI - [The role of troop on-the-job training in the system of schooling for military medical personnel]. PMID- 1887601 TI - [Work experience in the instruction and education of military physicians and pharmacists in the traditions of military medicine]. PMID- 1887602 TI - [The individualized instruction of students in a department of surgery]. PMID- 1887603 TI - [The esthetic education of students in a department of military field (military naval) surgery]. PMID- 1887604 TI - [Practical games in studying the organizational problems of military field surgery]. PMID- 1887605 TI - [The etiological diagnosis of nonclostridial anaerobic organic infection of the hepatobiliary system in military medical institutions]. AB - The results of B-bile bacterial examinations of patients who had undergone operations on biliary tract for acute or chronic cholecystitis in the military medical institutions of the USSR and the USA were retrospectively compared. Distinctive and similar features were revealed. The leading role of bacteroids, anaerobic found bacteria and clostridia was ascertained during the studies of etiological structure of anaerobic biliary infection. As for nonclostridial anaerobic infection of biliary tract, the polymicrobiotic process of aerobic and anaerobic associations is more typical. The centralization of bacteriological examinations in specialized "anaerobic" laboratory may improve the efficiency of microbiological diagnostics of nonclostridial anaerobic infection. PMID- 1887606 TI - [Experience in evx47ating the wounded and ill by rail during the war years and its application to extreme situations in peacetime]. PMID- 1887607 TI - [Lipid peroxidation and its interrelation with the personality characteristics of surgical patients]. AB - The article deals with the exam results of 42 pre- and postoperative surgical patients. The reactivity of peroxide oxidation of lipids plays an important role in regulation of adaptive process of surgical patients. The authors emphasize the role of anxiety state as one of the most intimate and obligate mechanisms of psychologic stress. The anxiety rising process influences upon the formation of typical psychophysiological correlations that lead to the intensification of lipid oxidation. PMID- 1887608 TI - [The use of sipralin in the local treatment of suppurative wounds]. PMID- 1887609 TI - [The use of roentgenography with multiple magnification for the follow-up of the reparative processes in the carpal bones]. PMID- 1887610 TI - [The classification and diagnosis of rheumatic diseases]. PMID- 1887611 TI - [The significance of changes in the R and Q waves on the ECG during bicycle ergometry in the diagnosis of stable stenocardia]. PMID- 1887612 TI - [The potentials for the prognosis of recurrences and the treatment characteristics of patients with the frequently relapsing form of peptic ulcer]. PMID- 1887613 TI - [The epidemiology of wartime]. PMID- 1887614 TI - [The definition of the concept of the "health and hygiene situation" and the gradations in its assessment]. PMID- 1887615 TI - [Mathematical modelling of the estimates of the demand for medical stores]. AB - Rapid and simple calculations make it possible to get precise data for requirements estimate of medical supplies, including opportune replacement of medicaments and other disposables which have a reduced period of storage, etc. The calculations of weight and volume of medical supplies give the possibility to evaluate transport and depot requirements. This mathematical model is destined for projection of automatic information systems in the interests of medical supplies. PMID- 1887616 TI - [Bed specialization in the evacuation hospitals of the People's Commissariat of Public Health of the USSR]. PMID- 1887617 TI - [The construction of a general theory of physical therapy]. PMID- 1887618 TI - [Balneotherapy and the immune status of the skin]. PMID- 1887619 TI - [The differential assessment of the meteorological conditions for aeroheliotherapy at the health resorts in the southern Far East]. PMID- 1887620 TI - [The effect of acupuncture on the hemodynamics and tolerance for physical loads in patients with cardiovascular diseases]. AB - Discontinuation of chemotherapy substituted for a course of acupuncture and electroacupuncture in 124 patients with coronary heart disease, essential hypertension and neurocirculatory dystonia resulted in a positive response of cerebral and peripheral hemodynamics, myocardial contractility and diastolic function. Myocardial hypertrophy regressed, exercise tolerance enhanced. Reflex activation of stress-limiting systems arresting excess adrenergic action on circulation is probably responsible for these phenomena. PMID- 1887621 TI - [Transcutaneous electric nerve stimulation in the therapy of threatened abortion]. PMID- 1887622 TI - [Low-frequency ultrasound in the treatment of osteoarthrosis patients]. PMID- 1887623 TI - [Clinical and experimental research on a massage cream in physiotherapeutic practice]. AB - New Bulgarian preparations from mioton series (A, B and C) have of late attracted the attention of clinicians. Of a special interest for physiotherapists is mioton B. Broad-scale clinical and experimental trials (41 patients and 75 animals) demonstrated high clinical efficacy of the cream mioton B (Extr. caps. spis. 1.01% 01. bergamotae u ol. lavandulae) induced by ultraphonophoresis. No side effects were registered. PMID- 1887624 TI - [The principles of the action of physiotherapy and health resort treatment]. PMID- 1887625 TI - [The choice of the type of electrophoresis by the leukocyte reaction in patients with a lung inflammation]. PMID- 1887626 TI - [The acupuncture stimulation of the hand points in hypertension patients with different types of blood circulation]. PMID- 1887627 TI - [The effect of sodium chloride sulfate water on blood lipid peroxidation in liver lesions]. PMID- 1887628 TI - [The effect of naftusia mineral water on gastric acid formation]. PMID- 1887629 TI - [Laser therapy combined with the phonophoresis of pelan ointment in the treatment of psoriatic arthritis]. PMID- 1887631 TI - [The development of folk medicine in China and the prospects for cooperation]. PMID- 1887630 TI - [Therapeutic gymnastics in transplantation of the flexors of the crus to the anterior surface of the thigh]. PMID- 1887632 TI - [Our initial experience of direct professional ties with partners from the People's Republic of China]. PMID- 1887633 TI - [A new technology for preserving the biological activity of mineral waters far from their sources]. PMID- 1887634 TI - [Shumak mineral waters]. PMID- 1887635 TI - [Current deontological problems in physiotherapy]. PMID- 1887636 TI - [The methods of Chinese self-massage]. PMID- 1887637 TI - [The physiotherapy of patients with chronic nonspecific prostatitis]. PMID- 1887638 TI - [Principles and perspectives of cancer chemoprevention]. PMID- 1887639 TI - [Carcinogenic hazards of radioactive cesium]. PMID- 1887640 TI - [Malignant neoplasm morbidity in the USSR in 1985-1989]. PMID- 1887641 TI - [Cytoplasmic receptors of steroid hormones and clinico-morphological characteristics of skin melanoma]. AB - Receptors of estrogens (ER), progesterone (PR), glucocorticoids (GR) and androgens (AR) were assayed in samples obtained from 142 patients with malignant melanoma. GR were observed most often (57% of cases), the percentage being significantly lower for ER (25%) and PR (18%) and extremely low for AR (4%). The occurrence of GR was significantly higher in metastasis to lymph nodes (69%) and soft tissue (67%) as compared to primary tumor (39%). It was higher in acro lentiginous melanoma (83%) than in superficially extending (30%) or nodular one (33%). GR occurrence rose with the increase in level of invasion (from 30% for level III to 71% for level V) and tumor thickness. In application of adjuvant chemotherapy, patients with GR--negative tumors tended to survive better than those with GR--positive tumors whereas in the chemotherapy-naive group, GR- positive tumors carried better prognosis. PMID- 1887642 TI - [Psychological component of fight against smoking in the framework of primary prevention of pulmonary cancer]. AB - The study discusses certain aspects related to primary prophylaxis of lung cancer. These include objective parameters of smoking and psychological aspects of tobacco dependence of smokers as well as their awareness of health hazard of tobacco and motivations for cessation of smoking. Social and psychological reasons and patterns of smoking were studied in 400 workers and clerks of industrial enterprises. The role of psychological factors in cessation of smoking was shown. The need for certain psychologic correction aimed at formation of healthy life style is emphasized. PMID- 1887643 TI - [Excretion of nitrates with saliva and urine and nitrite excretion with saliva in patients with chronic gastritis and duodenal ulcer]. AB - The study assessed excretion of nitrates in urine and saliva and that of nitrites with saliva of patients suffering gastric and duodenal ulcer. In both study groups, a positive correlation was established between nitrate concentration in saliva, on the one hand, and that in urine, and nitrite level in urine, on the other. The groups failed to show a difference in nitrate concentrations in either urine or saliva. Since retention of nitrates in the body of chronic gastritis patients held as precancer of the stomach proved no higher than that in patients with duodenal ulcer, the authors cast doubt on endogenous nitroso compounds as a cause of gastric cancer in cases of chronic gastritis. PMID- 1887644 TI - [Radiotherapy of malignant tumors in children]. AB - Radiation treatment is widely used in pediatric cancer patients. Much attention should be paid to preserve the function and structure of normal organs and tissues adjacent to tumor. To achieve this goal, optimal treatment modality should be chosen and closely followed. Certain peculiarities of irradiation of children, particularly, infants should be considered. These include the use of medication sleep. Drug combinations to be used to prepare patients for radiotherapy are discussed. PMID- 1887645 TI - [Complex treatment of locally advanced soft tissue sarcoma of the limbs]. AB - The experience of treatment of 40 patients with locally-advanced soft tissue sarcoma of the limbs. Treatment included preoperative chemoradiotherapy in combination with electromagnetic hyperthermia. As a result, 38 (95%) patients showed marked response which allowed radical limb-saving surgery whereas in 2 (5%) amputation was performed. Adjuvant chemotherapy was used for anaplastic tumors. Five-year survival rate was 64.7 +/- 6.7%. PMID- 1887646 TI - [Treatment tactics in giant cell tumor of the bone]. AB - The data on 76 patients treated for benign or malignant giant-cell tumor (GCT) of the bone are presented. Surgery involving bone reconstruction and endoprosthetics was the basic therapeutic procedure. Cases with lytic benign GCT received 36-40 Gy of radiation prior to surgery whereas whose with malignant tumors were subjected to complex treatment including preoperative irradiation, surgery and chemotherapy. Recurrence was observed in two patients with benign and in one- with malignant GCT. There were four fatalities. Five-year survival was 82%. PMID- 1887647 TI - [Organization of radiotherapy of patients with cancer of the mouth]. AB - During the last 15 years, the incidence of oropharyngeal cancer in the Chelyabinsk region increased from 2.0 to 5.7 per 100,000 of population. Lethality was 2.8 per 100,000. The radiological service of the region includes 4 radiological departments with a total of 270 beds equipped with 7 and units for gamma-ray teletherapy whereas in the oncological dispensary intrathecal gamma-ray therapy can be performed. Under these conditions, it is justified to plan treatment in the regional dispensary and to carry out gamma-ray teletherapy in the radiological department located most closely to the patient's place of residence whereas interstitial therapy should be performed in the dispensary. The said approach assured higher efficacy of treatment, better psychosocial status of patients and shorter duration of therapy; it holds promise for tumors of other sites requiring complex and costly procedures of intrathecal irradiation. PMID- 1887648 TI - [Puncture biopsy of the breast (debatable problems)]. AB - The reliability of puncture biopsy of the breast is 65%. The procedure is not safe since it does not assure ablasticity. Puncture biopsy should be performed immediately before the start of treatment at institutions equipped for cytological, surgical and radiation treatment. The use of the procedure should be confined to cases in whom morphologic data are decisive for choosing therapeutic modality. PMID- 1887649 TI - [Improved classification of x-ray images of the breast parenchyma]. AB - Classification after J. Wolfe is the most popular classification of mammographic images of the breast to date. It distinguishes four (N1, P1, P2 and DY) types of breast parenchyma according to size of a shadow observed. P2 (subtotal) and DY (total involvement) types imply the highest risk of cancer. The study showed that criteria of the types distinguished are indistinct making it difficult to identify true high risk conditions. It is suggested that J. Wolfe's classification be detailed further, viz. conditions with and without nodular structures (N+ and N0) should be distinguished as well as types with homogeneous and nonhomogeneous non-nodular structures (P1a, P1b, P2a, P2b, etc.). The analysis of 167 mammograms of verified cancer and precancer showed the modified classification to more clearly identify various types of breast parenchyma and to more reliably define those carrying the highest risk for cancer. PMID- 1887650 TI - [Optimal effect of one-stage radical surgery in malignant tumors of the esophagus]. PMID- 1887651 TI - [The value of placental histology for the detection of genetically-induced abortions]. AB - The majority of early spontaneous abortions is caused by genetic disorders. Chromosomal aberrations do not only imply characteristical morphologic alterations in embryo/fetus, but also in chorionic villi. Its possible to draw conclusions through the combination of a small amount of histological findings on chorionic villi to explain the kind of aneuploidy. Among 968 early spontaneous abortions 18.3% were defined as genetically caused by histological examination. 87.6% are probably trisomies, 7.3% polyploidies. 5.1% were diagnosed as complete hydatidiform moles with a diploid, androgenetic chromosome set. The value of histological examination of early spontaneous abortion tissue are discussed and it is pointed out to remaining problems. In a different percentage it is possible to establish the type of aneuploid by microscopic examination alone. Frequently there are sings to allow the conclusion there is a developmental disorder like genetic aberration. PMID- 1887652 TI - [Vaginal sonographic follow-up of embryo development]. AB - The clinical study reports on facilities of transvaginal sonography to demonstrate early embryological structures. A collective of 659 sonographical examinations in 593 women between 4. and 13. week of gestation (wog) is described. The earliest imagery of an intrauterine pregnancy could be performed at 28. day post menstruation (p.m.) and first heard beats could be detected at 36./37. day p.m.. The secondary yolk sac could be discovered at the end of 5. wog and first motions of the embryo in 8. wog. Certain structures as parts of the skull, brain and spine were clearly to be differentiated in 10.-12. wog. Transvaginal sonography renders an very early and comprehensive control of regular embryological growth and development. Striking malformations are early detected. PMID- 1887653 TI - [Doppler sonography--effect of fetal position, site of the placenta and measurement site of the fetal aorta]. AB - The influence of fetal position, the site of placenta and the site of measurement in the fetal aorta on doppler-flow parameters was investigated in patients with uncomplicated pregnancies. In 20 cases the S/D-ratio was obtained in three different regions of the descending aorta. Measurements superior the renal vessels showed comparable values (4.1-4.3). No differences were found between signals obtained cranial or caudal of the diaphragma. Measurements at the aortal bifurcation showed significantly increased median values (6.6, p less than 0.05). No differences could be obtained concerning the influence of fetal position or site of placenta on S/D-ratio. All median values of a total of 197 patients were in the range of 4.8. Therefore it may be concluded that the above mentioned parameters do not have significant influence on doppler flow parameters in fetal vessels. However, a proximal site of measurement in the descending aorta fetalis should be reassured. PMID- 1887654 TI - [Comparison of duplex systems and simple Doppler equipment in obstetric diagnosis]. AB - Duplex systems are normally used in obstretric Doppler sonography. The fact that these systems are technically complex and very costly to some extent contradicts the use of Doppler sonography as a screening method. This study examines whether simplex Doppler systems without tomographic imaging and not involving costly technology, such as frequency analysis, are as suitable for Doppler examination in pregnancy as the costly duplex systems. Examinations of 83 patients between GW 32 and 42 showed that both the umbilical and uterine arteries can be reliably identified using the simplex Doppler unit. A comparison of Doppler curves obtained with duplex and simplex Doppler systems showed that the two devices produced the same results. The Doppler curves were compared both as regards their geometry, according to the score described by Fendel et al. (1988), as well as on the basis of calculated parameters. The scores were correlated to delivery mode and birth weight. However, the fetal aorta cannot be reliably located with the simplex Doppler unit unless it has been tomographically imaged beforehand. Doppler examination of the umbilical and uterine arteries provides the best information for selection of high-risk pregnancies. It therefore appears sufficient to screen patients with the simplex Doppler described here and to perform more detailed diagnostic investigations with a duplex systems in the event of pathologic findings. PMID- 1887655 TI - [Assisted spontaneous delivery vs. Bracht manual aid within the scope of vaginal delivery in breech presentation. Late morbidity in children 5-7 years of age]. AB - For judgment of late morbidity we investigated 52 children after vaginal delivery in breech presentation age from 5 to 7 years. This concerned 27 children after assisted spontaneous labour and 25 children after manual expression according to Bracht. All the children were mature and eutrophic and without neonatal distress after delivery. They were explored with help of an voluminous screening programme, concerning not only the intellectual development but also the psychomotoric capacity. The result was an very high intellectual conduct in frame of the test according to Raven (PR greater than 75). The difference in confrontation to the collective after manual expression according to Bracht was statistical significant (p less than 0.05). Neuropsychologic investigations according to Simernitzkaja demonstrated evident differences in disfavour to children after manual expression according to Bracht concerning the visual memory performance for symbols and letters. Further investigations referring to the graphomotoric accomplishment of one hand or both hands reinforced the opinion; that means the visual motoric totality performance in a narrowed sense or the psychomotoric performance in a enlarged sense was statistical significant poorer pronounced (p less than 0.05). The results underline the claim to estimate more critical the manual expression according to Bracht till now. PMID- 1887656 TI - [Diabetes in pregnancy--an underestimated risk?]. AB - During the period 9/86 to 12/89 among a total of 60 diabetic pregnant women we analyzed 32 patients with gestational diabetes concerning diagnosis at admission and time of giving the diagnosis as well as the beginning and management of insulin therapy. Pregnancy complications and fetal outcome were related to these data. The perinatal mortality rate ranged 3.1% and was exclusively caused by 2 intrauterine deaths. Until a screening program perhaps will be introduced in the context of the nationwide Prenatal Care Program it is required that obstetricians and internists have to search intensively for impaired carbohydrate metabolism in pregnant women. PMID- 1887658 TI - [Cesarean section in an 11-year-old girl]. AB - We report about a term pregnancy in an eleven year old girl (51 kgs, 152 cm). At the end of the second stage of labour, the pregnancy was terminated by caesarean section for relative disproportion. The child was a healthy boy (3080 g, 53 cm). The mother accepted the child in spite of severe problems. She left the hospital on the 13th postoperative day. PMID- 1887657 TI - [Maternal and fetal metabolic parameters in acute and chronic fetal malnutrition]. AB - The respiratory pathophysiology of placental insufficiency is well understood, whereas the metabolic effects of chronical or acute malnutrition still need further evaluation. In a comprehensive study of 20 deliveries respiratory parameters and substrates of carbohydrate- and lipid-metabolism were analysed simultaneously from maternal blood at 4 cm dilatation, at cord clamping immediately delivery and 2 hours post partum as well as from arterial and venous umbical blood samples. Normal deliveries were compared with cases of fetal retardation and moderate acute fetal acidosis. For glucose, insulin, c-peptide and pyruvate a strong rise in maternal blood during labour was observed as well as for the non-esterified fatty acids (NEFA), which have a high materno-fetal gradient. Arterio-venous differences of concentrations were found in the umbilical cord blood for glucose, pyruvate and NEFA. In cases of chronical insufficiency of the placenta especially elevated lactate levels were measured, whereas a moderate fetal acidosis obviously leads to an additional feto-maternal pyruvate transfer. The results lead to the conclusion that the fetal metabolism has considerable means of adaptation during delivery even under chronical or moderate acute stress conditions. PMID- 1887659 TI - Investigations on the ethnic variability of the ABO blood group polymorphism in Iran. AB - 112 Iranian population samples with a total of 600954 individuals are analyzed concerning the ethnic variability of ABO allele frequencies. The genetic heterogeneity within and between these population samples is considerable. This heterogeneity is discussed with regard to the ethnohistory of Iran. The most striking ABO allele frequencies are observed in Assyrians, Armenians and Zoroastrians, which differ extremely from that of all the other hitherto studied ethnic groups of Iran. Obviously varying ABO allele frequencies are seen also in Yazdis as well as in Turkomans and Arabs living in Iran. And finally the Iranian Jews reveal clear frequency differences in comparison with all the other Iranian population groups. It can be assumed that the specific ABO allele frequencies found in the above mentioned ethnic groups are connected with their different geographical origin as well as with their marked endogamy. PMID- 1887660 TI - Correlation of skeletal maturation with stature and body weight of southern Chinese girls in Hong Kong. AB - Correlations of skeletal maturation with stature and body weight were studied in one hundred and seventeen Southern Chinese girls aged eleven years nine months and twelve years three months born and brought up in Hong Kong. The skeletal maturation was assessed from the left hand and wrist radiographs by the Greulich and Pyle Atlas Method. The early maturers in skeletal development were significant taller and heavier than the late maturers with p less than 0.001. PMID- 1887661 TI - Elastic mechanisms in primate locomotion. AB - Tendons that stretch elastically and recoil, as the forces on them rise and fall, can save energy in running by enabling the animal to make do with shorter or slower muscle fascicles, that can generate force more economically. Non-human primates have rather long fascicles and thick tendons in their distal leg muscles and so seem poorly adapted to save energy in this way. Additional savings are made possible by the elastic compliance of ligaments in the foot. Though tendon and ligament compliance tend to save energy, the compliance of branches tends to increase the energy cost of arboreal locomotion. PMID- 1887662 TI - [Functional interpretation of the dimensions of the pelvis of Australpithecus afarensis (AL 288-1)]. PMID- 1887663 TI - Muscle fibre and tendon lengths in the distal limb segments of primates. AB - The dimensions of the distal leg muscles in ten different primate species were examined in order to determine whether locomotor specialization is reflected in the fibre and tendon lengths of these muscles. For comparative purposes a non primate was also included in the study. The locomotor specializations displayed by the investigated species were leaping, quadrupedal walking or running on the ground, quadrupedal climbing, and brachiation. After removal of the muscles and measurement of their free tendon lengths, fibres were isolated from several locations in the muscle and their lengths measured. Statistical tests revealed some differences between the species in fibre and tendon lengths. These did not show a consistent correlation with the locomotor specialization. It was concluded that every primate species has the potential to perform a variety of movements and to specialize in any locomotor mode. PMID- 1887664 TI - The jump as a fast mode of locomotion in arboreal and terrestrial biotopes. AB - The jump is always used for locomotion. For its execution in arboreal and terrestrial biotopes the requirements are of somewhat different nature. In an arboreal biotope the jump is characterized by a rapid progression through discontinuous substrates and the ability to take off from a small area and a secure landing on a spot. This requires well coordinated movements in all phases of the jump. On the ground, the jump is less frequent and often used for crossing obstacles or gaps. In primates both variants can be observed. In order to relate the details of locomotor behaviour to a certain environment, the biomechanics of jumping are analyzed in five primate species: The three mainly arboreal prosimian species Galago moholi, the smallest and most specialized leaper of all, Galago garnettii, a medium-sized bushbaby with some capacities for jumping, and Lemur catta also with some abilities to jump. The two simian species, Macaca fuscata and Homo sapiens, are usually terrestrial and have good jumping capacities, although not in terms of quantity. The investigation is based on high-speed motion analyses (100-500 frames/second) and the synchronized records of a force plate from which all subjects had to jump off. On the basis of the results two kinds of jumping can be distinguished: standing and running jumps. The three prosimian species perform standing jumps. Dorsiflexion of their tails compensates ventrally oriented rotational moments of the trunk during body extension at take off. The upward arm swing yields an overall increase in take-off velocity without additional muscular force exerted by the legs. The main difference among the species are the high relative forces in the small Galago moholi (up to 13 times body weight) as compared to the larger G. garnettii (8.5 times body weight) and the even larger Lemur catta (4.5 times body weight). In Homo sapiens the standing jump is characterized by an extensive arm swing backward, which is then followed by a forward and upward movement. The velocity at take-off is much smaller if compared to the prosimians. The running jump in Macaca fuscata is always preceded by at least one gallop cycle. The body assumes a ball shape at the beginning of the actual take-off. This is advantageous for rotating the body into a position in which the trunk axis is in line with the direction of movement. The tail of the Japanese macaque is too short to compensate the trunk's lift exerted on the hip region by the extending hindlimbs.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1887665 TI - Toward the locomotion of two contemporaneous Adapis species. AB - The morphological differences between the limb bones of two Adapis species from two localities in Southern France are analyzed for their functional significance. The study focuses on the distal humerus, proximal femur, astragalus and calcaneum. The Escamps species Adapis aff. betillei shows more extreme flexion at the elbow, lateral mobility at the hip, and more rotation at the calcaneocuboid joint than in the other species. The species from Rosieres 2 A. cf. parisiensis shows increased emphasis on parasagittal movements, restrictions of lateral mobility in the hindlimb, enhanced capacity for rapid flexion and powerful extension of the thigh, and powerful rapid foot extension. The Rosieres species probably engaged in more frequent branch walking and running, and the Escamps species probably included more climbing in its locomotor repertoire. In the general Adapis genus morphology, the large tuber calcanei, short astragalus, and the presence of a calcaneal "pressure facet" are similarities shared with living cercopithecids. Along with other characters, these suggest that horizontal running was possibly an important means of locomotion in the Adapis and adapine morphotypes, and may even indicate a degree of terrestraility. Contrary to the most common view, the euprimate morphotype was probably not a specialized leaper. PMID- 1887666 TI - Human body proportions explained on the basis of biomechanical principles. AB - On the basis of theoretical biomechanics and of experiments, we investigated the mechanical requirements to which the body of a bipedally walking primate is subject, and the possibilities to meet these requirements with a minimum amount of energy. The least energy-consuming adaptation is clearly a body shape favourable for the preferred locomotion. Some characteristics of human body shape, in particular its proportions, could be identified as advantageous for fulfilling obvious biological roles or mechanical necessities. The characteristic length and the extended position of human hindlimbs make walking faster without additional input of energy. Mass distribution on the hindlimbs reduces the energy necessary for accelerating the swing limb after liftoff and for decelerating the swing limb before the heelstrike. Length and mass distribution in the forelimb gives it a pendulum length comparable to that of the hindlimb, so that both extremities swing at the same frequency. This swinging of the forelimbs counters in part the movements exerted by the moved hindlimbs on the trunk. The elongate and slim shape of the trunk provides great mass moments of inertia and that means stability against being flexed ventrally and dorsally by the forward and rearward movements of the heavy and long hindlimbs. Shoulder breadth in combination with the shallow shape of the thorax yield higher mass moments of inertia against the rotation of the trunk about a vertical axis than a cylindrical trunk shape. Further elongation of the hindlimbs is limited by the energy necessary for acceleration and deceleration, as well as for lifting them during the swing phase. In addition, the reaction forces exerted by the hindlimbs would expose the trunk to undue excursions if the proportions trunk length/limb length or trunk mass/limb mass would decrease. The above-noted kinetic requirements are partly in line, partly in conflict with the requirements of statics. PMID- 1887667 TI - Tooth crown heights, tooth wear, sexual dimorphism and jaw growth in hominoids. AB - The aim of this review is to bring together data that link tooth morphology with tooth function and tooth growth: We aim to show how the microanatomy of hominoid teeth is providing evidence about rates of tooth growth that are likely to be a consequence of both masticatory strategy and social behaviour. First, we present data about incisor and molar tooth wear in wild short chimpanzees that demonstrate how crown heights are likely to be related to relative tooth use in a broad sense. Following this we review recent studies that describe the microanatomy of hominoid tooth enamel and show how these studies are providing evidence about tooth crown formation times in hominoids, as well as improving estimates for the age at death of certain juvenile fossil hominids. Next, we outline what is known about the mechanisms of tooth growth in the sexually dimorphic canine teeth of chimpanzees and compare these patterns of growth with tooth growth patterns in the canines of three fossil hominids from Laetoli, Tanzania. Finally, we discuss how selection pressures that operate to increase or reduce the size of anterior teeth interact with jaw size. We argue that the space available to grow developing teeth in the mandibles of juvenile hominoids is determined by the growth patterns of the mandibles, which in turn reflect masticatory strategy. The consequences of selection pressure to grow large or small anterior teeth are likely to be reflected in the times at which these teeth are able to emerge into occlusion. PMID- 1887668 TI - Interleukin-1 derived synthetic peptide as an added co-adjuvant in vaccine formulations. AB - A synthetic peptide containing the immunostimulatory and receptor binding sequences of human IL-1 beta was synthesized and tested for its immunoadjuvant properties. Using a commercially available hepatitis B vaccine as model antigen we found that added peptide enhanced both total and protective antibody responses in high and low responder strains of mice but was unable to overcome non responsiveness in a third strain. Increased antibody response to antigen in the responder strains was not accompanied by any significant alteration in IgG isotype composition. These results suggest that this peptide may prove useful as a co-adjuvant in vaccines. PMID- 1887669 TI - Principles of selective inactivation of viral genome. VI. Inactivation of the infectivity of the influenza virus by the action of beta-propiolactone. AB - The kinetics of inactivation of the infectivity of the influenza virus by beta propiolactone have been studied. Rate constants have been determined for inactivation of the A/Leningrad/385 (H3N2) and B/Leningrad/489/80 influenza virus under the action of beta-propiolactone on a virus-containing allantoic fluid and on a purified viral suspension. The data obtained allow calculation of the time required for inactivation of the influenza virus infectivity to a given extent in virus-containing solutions at any initial concentration of beta-propiolactone. PMID- 1887670 TI - Revaccination with pneumococcal vaccine of elderly persons 6 years after primary vaccination. AB - We vaccinated 15 persons, age 56 to 79 years, with 14-valent pneumococcal polysaccharide vaccine and revaccinated them with 23-valent vaccine 6 years later to assess adverse reactions and booster responses of anticapsular antibodies. No systemic reactions occurred after administration of either vaccine. After booster vaccination, five vaccinees developed only mild soreness or tenderness at the site of injection. The (arithmetic) mean antibody level to 12 capsular types measured by radioimmunoassay increased 3.1-fold 1 month after the first vaccine; the range was 1427-5124 ng antibody nitrogen per ml (N ml-1). Six years later, mean antibody levels waned to about half these levels. One month after administration of the second dose of vaccine, the mean antibody level increased 1.5-fold; the range was 1011-3954 ng antibody N ml-1. Revaccination with pneumococcal vaccine of elderly persons can be carried out safely; the levels of anticapsular antibody achieved after revaccination are about half the levels after primary vaccination. PMID- 1887671 TI - The adjuvanticity of Algammulin, a new vaccine adjuvant. AB - Algammulin is a suspension of 1-2 microns ovoids of the immune stimulant gamma inulin (g-IN) in which alum is embedded as a carrier for protein or other anionic antigens. Tests for specific IgG and seroconversion responses in mice immunized with keyhole limpet haemocyanin (KLH) show that the presence of g-IN on the alum has increased its adjuvanticity 6- to 17-fold (p less than 0.001), and thus has a synergistic effect. A mixture of alum and g-IN was no more active than alum alone. Low KLH doses at borderline seroconversion levels (0.1-1 microgram/mouse) allow comparison with a vaccine situation. The improved Algammulin responses extended to 58 days after primary doses and to memory recall after boost at 65 days. At 1 mg Algammulin i.p. in primary and secondary doses the anti-KLH IgG responses were equal to those from Freund's complete adjuvant. The g-IN on the alum increased all responses tested (IgG 1, 2a, 2b, 3 and total IgG, IgM, IgA and IgE), but changed the emphasis from that of alum (favouring mostly IgG 2a, IgG 2b and IgA). PMID- 1887672 TI - OmpB (osmo-regulation) and icsA (cell-to-cell spread) mutants of Shigella flexneri: vaccine candidates and probes to study the pathogenesis of shigellosis. AB - Genetic and molecular data now available on the pathogenic properties of Shigella flexneri allow rational design of live attenuated vaccine strains. The genes required at given steps of the infection process can be selectively mutated to impair the bacterium's capacity to interact with intestinal epithelial cells and/or survive within intestinal tissues in general. We have tested two mutations in S. flexneri serotype 5a (M90T) which, alone or in combination, have yielded promising results when evaluated as vaccine prototypes in orally infected macaque monkeys. The first mutation, icsA, blocks intracellular and cell-to-cell spread of the micro-organism. This mutant (SC560) appeared reasonably well tolerated and elicited protection against homologous challenge. The second mutation, ompB, disconnects the bacterium from one of its major environmental regulatory factors, osmolarity. This mutant (SC433) still caused slight dysenteric symptoms in vaccinees. It was also perfectly protective. When these two mutations were combined, the double mutant (SC445), was perfectly tolerated but failed to protect one out of five animals. These studies bring interesting prospects of the possibility of immunizing against shigellosis. In addition to providing new possibilities for vaccine design, construction and evaluation of these mutants allowed substantial progress in understanding the pathogenesis of shigellosis. PMID- 1887673 TI - Different profiles of the human immune response to primary and secondary immunization with an oral Salmonella typhi Ty21a vaccine. AB - Human immune response to a secondary immunization by the oral route was studied by enumerating specific antibody-secreting cells (ASC) in the peripheral blood, believed to reflect the local immune response in the mucosa. The volunteers had been immunized 1-2 years earlier with live Salmonella typhi Ty21a given orally as three doses of vaccine in enteric-coated capsules (3 x E); their ASC and serum antibody responses have been published. In the present study 17 of the same volunteers received one booster dose of the same vaccine (B-E). Specific ASC appeared in the blood of all volunteers after vaccination, peaked on day 5 and faded away thereafter so that on day 9 specific ASC were detected in only seven subjects. The ASC responses to the single booster dose were significantly higher than those to one dose in primary immunization and at least as high as those of the same volunteers to three doses in primary immunization. Serum antibody responses were not seen in any of the vaccinees after secondary immunization, whereas after primary immunization 60% of these subjects responded. This study shows the presence of immunologic memory also in respect of the human ASC response, and confirms the separate nature of ASC and serum response. PMID- 1887674 TI - Active immunity is seen as a reduction in the cell response to oral live vaccine. AB - Oral immunization elicits a response of antibody-secreting cells (ASC) in the peripheral blood; these cells are believed to originate in the mucosa and hence give information on the mucosal immune response. We have shown earlier that oral booster immunization is followed by an elevated ASC response reflecting an immunologic memory. In the present study we show that a booster dose of a live bacterial vaccine given at a time of active mucosal immunity elicits a low ASC response only. This is probably because the multiplication of the live vaccine is inhibited in the gut, resulting in a low actual dose of the antigen. This situation may be an example of the protective immunity manifested when an orally immunized person encounters the pathogen in nature, and could be used to assess the protective immunity. PMID- 1887675 TI - Effective postexposure treatment of rabies-infected sheep with rabies immune globulin and vaccine. AB - An experiment to assess the efficiency of the treatment recommended for humans after exposure to rabies was conducted in 68 sheep experimentally infected with a fox rabies virus. The infected sheep were divided into three groups and were given either a cell-culture vaccine (on the day of infection, then at day 3, 7, 14), human rabies immunoglobulin (26 IU kg-1 on the day of infection) or a combination of the vaccine immunoglobulin. The latter combination was the only treatment found to be effective in 100% of the animals, as 71% of the controls died. This model appears to be useful in assessing new regimens of postexposure treatment for humans as well as in the reconsideration of its feasibility, or validity, in animals. PMID- 1887676 TI - High antibody responses in rabbits immunized with influenza virus ISCOMs containing a repeated sequence of the Plasmodium falciparum antigen Pf155/RESA. AB - Immunostimulating complexes (ISCOMs) are spherical structures where immunogens are presented as multimers in a matrix of the adjuvant Quil A. ISCOMs have been shown to enhance the immunogenicity of several antigens important to both human and veterinary vaccine development. We have coupled a fusion protein, designated ZZ-M2, comprising eight copies of the C-terminal repeat subunit EENV of the Plasmodium falciparum blood-stage antigen Pf155/RESA and two IgG-binding domains of staphylococcal protein A (SpA), to preformed influenza virus envelope protein ISCOMs. Rabbits immunized with the conjugated ISCOMs produced high titres of antibodies even after the first injection. These antibodies reacted with the EENV repeat sequence in ELISA and with Pf155/RESA in immunofluorescence on infected erythrocytes. The antibody response, which was sustained for more than 20 weeks, was efficiently boosted and superior or equal to that obtained after immunization with ZZ-M2 in Freund's complete adjuvant. In contrast, the antibody response induced in rabbits immunized with ZZ-M2 in Syntex Adjuvant Formulation-MF (SAF MF) was weak and of short duration. The antibodies produced after immunization with ZZ-M2 coupled to influenza virus ISCOMs mainly recognized epitopes formed by two or more EENV subunits and were highly specific for Pf155/RESA. Furthermore, the antibodies efficiently inhibited merozoite reinvasion of erythrocytes in vitro, indicating that they recognized epitopes exposed on the native antigen. In addition, the ZZ-M2-conjugated ISCOMs also induced high titres of antibodies reacting with SpA or the influenza virus envelope protein.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1887677 TI - [Changed working times require courage and new thinking]. PMID- 1887678 TI - [Service and love create work enjoyment]. PMID- 1887679 TI - [In Alternative Birth Clinics (ABC) midwives themselves lend a hand in spring cleaning]. PMID- 1887680 TI - [Reform in care for the aged is reform for women. Interview by Jan Thomasson]. PMID- 1887681 TI - [Prioritization flop for 500 million]. PMID- 1887682 TI - [Many question marks before move to communities]. PMID- 1887683 TI - [Lawyers are members' defense advocates. Interview by Elisabet Forslind]. PMID- 1887684 TI - [It was rarely only the nurse's fault. Interview by Elisabet Forslind]. PMID- 1887685 TI - [Cancer care in the home--a link between patient and hospital. Interview by Anna Olfsson]. PMID- 1887686 TI - [OSCAR groups (Nursing Care and Pain Relief for Cancer Patients) give Kerstin security]. PMID- 1887687 TI - [Nothing to report]. PMID- 1887688 TI - [Here we inform you how things go. "We want to stay behind in Saudi Arabia". Interview by Jan Thomasson]. PMID- 1887689 TI - [Hedvig Charlotta Nordenflycht (1718-1763)]. PMID- 1887690 TI - [The psyche and the person]. AB - Psychology and Psychopathology seem to neglect the clarification of the contents of their field of work. Not trying to interpret the reasons for this lack, the author suggests a definition for psyche and person. These definitions are deduced from known biological facts taking into account the limits of cerebral abilities. They are based on the results of Weinschenk's research in the field of Erkenntnistheorie who proved that the problem of psycho-physical interrelation in philosophy is a pseudoproblem. PMID- 1887691 TI - [Discussion comment on the contribution by E. Schulz and H. Remschmidt: Stimulant therapy of hyperkinetic syndrome in childhood and adolescence]. PMID- 1887692 TI - [Inpatient management of adolescent psychiatric patients. A single day study]. AB - The distribution of disorders in a one-day sample of 1806 adolescents receiving inpatient psychiatric care and classified with the diagnostic system ICD-9 is described. Of the inpatient psychiatric facilities for adolescents in the Federal Republic of Germany and West Berlin, 85% responded to our questionnaire. The main findings were: 1) More of the inpatients were male than female (1:0.8); 2) 80% of the patients were being treated at non-university facilities; 3) differences in diagnose between university and other hospitals were small and concerned only psychosis, eating disorders and oligophrenia; 4) the most frequent diagnoses were psychosis and neurosis (20% each), followed by special symptoms/syndromes and conduct disorders (between 10% and 15% each) and emotional disorders (10%); 5) other disorders were less common (under 10% each); 6) a comparison of the different Lander in the Federal Republic indicated that some regions do not have enough inpatient facilities. PMID- 1887693 TI - [Predictive value of psychiatric symptoms in the preschool age for adjustment in school age]. AB - This paper derives from a prospective cohort study conducted in Freiburg (Federal Republic of Germany) from 1979 to 1987 with 209 (follow-up outcome: 172) 3- to 5 year-olds. The "Behaviour-Screening Questionnaire," the "Children's Global Assessment Scale" and a thorough semi-standardized interview were used to identify behavior problems in the children. The results were analyzed in relation to life events, sex and socioeconomic status. They were compared with the findings in other studies. Most of the variables examined proved to be of low predictive value. The mood changes common in preschool and kindergarten children with behavior problems were no longer in evidence 7 years later. PMID- 1887694 TI - [Development-dependent diagnosis in two children with a rare "combined disorder of school readiness" in accordance with ICD-10, F81.3]. AB - The new category (ICD-10) of mixed disorder of scholastic skills (F81.3) includes the combination of specific reading and spelling disorders with specific disorder of arithmetical skills and the combination of specific spelling disorder with specific disorder of arithmetical skills. We could demonstrate such combinations of specific developmental disorders in two children. In addition to diagnostic approaches with standardized testing procedures we used a model that is based on the steps in the development of specific skills. This method can be helpful in determining what kinds of intervention would be most appropriate. Both children with mixed disorders of scholastic skills also had psychiatric disorders. PMID- 1887695 TI - [Selective visual attention and continuous attention in dyslexic children. An experimental study]. AB - Selective and sustained visual attention were tested in 29 boys with developmental dyslexia and 28 normal spellers (also boys) matched for age, grade in school, I.Q. and other developmental parameters. The developmental dyslexia group had deficits in selective attention. A significant effect of task difficulty was found. There was no dysfunction in sustained attention. PMID- 1887696 TI - [Diseases and causes of death in native wild birds--a literature review]. AB - Little attention was dedicated to diseases and causes of death of indigenous wild birds compared to poultry until recent decades. The interest of veterinary medicine in the spectrum of causes of morbidity and mortality of wild birds increased with the understanding of the importance of these birds as vectors in the epidemiology of zoonoses and as a biological indicator for the occurrence of substances noxious for the environment. The climate as a natural factor and the influences of civilization as traffic, high voltage lines and oil contamination of the sea lead to a reduction of bird species by starvation, traumata, intoxication and degenerative or proliferative and inflammatory or non inflammatory processes. Many parasitological, bacteriological, mycotic and viral diseases are wide spread among free living birds and make difficulties in keeping and breeding endangered birds. PMID- 1887697 TI - ELISA for assessing Toxoplasma gondii antibodies in pigs. AB - The ELISA technique was applied to assess Toxoplasma gondii antibodies in pigs. Among 925 swine examined 36.4 per cent of the animals were seropositive. Serum titres ranged from 100 to 3,200. PMID- 1887698 TI - Toxigenic Pasteurella multocida in rabbits with naturally occurring atrophic rhinitis. AB - In a commercial rabbitry nasal swabs were taken from 36 animals with enzootic upper respiratory disease resembling porcine atrophic rhinitis. 35 Pasteurella multocida strains were isolated from 17 rabbits. Among 30 strains tested for dermonecrotic toxin production 3, derived from 3 animals, were positive in the guinea pig skin test. 15 Bordetella bronchiseptica strains were recovered from 14 rabbits. No toxigenic strains were found among 6 isolates tested using the same method. PMID- 1887699 TI - [The possibility of the serological differentiation of Clostridium species using enzyme immunoassays]. AB - A method for serotyping and diagnosis of 30 selected Clostridia strains of 12 different species by an enzyme-immuno-assay using polystyrene balls as a solid phase is described and tested for its efficiency. The reference strains and the homologous test strains could be differentiated from the heterologous in principle. A reliable detection of the several serotypes of Cl. perfringens was not perfectly to achieve with the conjugates used here, cross-reaction with Cl. chauvoei could be removed by absorption. The conjugate of Cl. bifermentans reacted with Cl. sordellii and Cl. difficile too, and must be absorbed prior any diagnostic applications with vegetative cells of the corresponding strains. Concerning the antigenic relationships between the Clostridia strains used here, the results of Ellner and Green (7, 8) as well as of Poxton and Byrne (14) could be reconfirmed. Moreover the applied technique offers the possibility to come to a more detailed result concerning the degree of antigenic relationship. The developed method is a valuable tool for the differentiation of pathogenic Clostridia and within the group Cl. bifermentans/Cl. sordellii/Cl. difficile a rapid diagnosis at the species level could be achieved. Some limitations by cross reactions are given, but results can be improved by absorption of the conjugates. PMID- 1887700 TI - Chicken egg antibodies for prophylaxis and therapy of infectious intestinal diseases. V. In vivo studies on protective effects against Escherichia coli diarrhea in pigs. AB - A field study and a controlled infection trial showed the protective effect of egg yolk lyophilisate and whole egg lyophilisate against enterotoxic E. coli germs. The lyophilisates were gained from eggs of hens immunized against pilus antigen of porcine-enterotoxic E. coli. In a first field study using egg yolk antibodies, 92% of 299 diarrhea affected piglets were cured. In a further field study diarrhea affected piglets were cured after 3 days by application of egg yolk lyophilisate from immunized hens. Piglets treated only with egg yolk of not immunized hens showed no signs of recovery. The infection trial showed, that whole egg lyophilisate of immunized hens was as successful as a common antibiotic therapy in curing piglets, orally infected with 5 x 10(10) E. coli/feeding and animal. The present data show that chicken egg antibodies can be used for treatment of infectious diarrheal diseases in young animals. So far they represent a good alternative to the common used antibiotic therapy. PMID- 1887701 TI - Immunohistochemical detection of chlamydiae in formalin-fixed tissue sections: comparison of a monoclonal antibody with yolk derived antibodies (IgY). AB - Immunohistological detection of chlamydiae in formalin-fixed and paraffin embedded sections of various organs from several species is described. In a retrospective study, two antisera, a commercially available monoclonal murine antibody (IgMur) and vitelline immunoglobulins (IgY), extracted from the egg yolk of immunized hens, were compared and tested for their applicability under routine condition. Both antisera were applied to tissues from which chlamydiae had been isolated or in which the presence of chlamydiae had been suspected in specially stained sections. Antigen labelling was optimal with the monoclonal antibody. Vitelline immunoglobulins produced some unspecific reactions, especially in lung tissue sections. Because of the antigenic relationship between the vitelline antibodies and tissues of birds, IgY are not suitable for the detection of psittacosis on avian substrates, when using an indirect immunological method. Staining in other tissues e.g. intestine or placenta was of equal quality as that attained with monoclonal antibodies. Depending on the advantages and disadvantages in every individual case, one of the two antibodies may be chosen for further studies. Vitelline antibodies should be preferred with respect to animal welfare. PMID- 1887702 TI - Typing of Rhodococcus equi isolated from submaxillary lymph nodes of pigs in Japan. AB - Isolation of Rhodococcus equi from the submaxillary lymph nodes of pigs, with or without caseous lymphadenitis, and typing of the isolates by two serological methods were carried out. The rate of isolation of the organisms from the lymph nodes of pigs was 5 times higher in the lymph nodes with caseous lymphadenitis than in those without the lesion. Of 219 isolates, 146 (66.7%) were typable by the method of Prescott, while all the 219 isolates (100%) were typable by the method of Nakazawa et al. The most frequently isolated were serotype 2 of Prescott (identical to serogroup 16 of Nakazawa et al.), and serogroup 3 of Nakazawa et al., which did not correspond with any serotypes of Prescott. Serotypes/serogroups of R. equi from pigs were thus first clarified in Japan. PMID- 1887703 TI - [The interaction of Legionella pneumophila with different types of cell cultures and the effect of interferon preparations on this process]. AB - The interaction of L. pneumophila with lymphoblastoid cell cultures H9 and H9/IIIB and epithelial cell cultures HEp-2 mutual influence have been noted. L. pneumophila penetrates into cells HEp-2 and multiplies there due the so-called "spin phagocytosis". The study of the influence of the preparations of interferon, Leukinferon and Reaferon, on the adhesive capacity of bacteria and their penetration into eukaryotic cells has revealed that the preliminary treatment of both bacteria and cells HEp-2 with the preparations of interferon prior to their infection with Legionella leads to a decrease in the number of microorganisms associated with cells. PMID- 1887704 TI - [The genomic fingerprinting of the causative agents of sapronoses]. AB - The genome polymorphism of the causative agents of sapronoses (Vibrio cholerae, Legionella and Leptospira) has been studied. The use of the method of genome fingerprinting [correction of dactyloscopy] has been shown to permit the differentiation of closely related strains of such causative agents. The epidemically significant strains of the causative agents of sapronoses, isolated in different geographical regions, have been found to be genotypically related, i.e., they are probably of clonal origin. Avirulent and nontoxigenic strains are genotypically heterogeneous and differ both from one another and from epidemically significant strains. Using V. cholerae as an example, the hypothesis of the appearance of potentially dangerous variants at the epidemic period in the absence of their release at the period between epidemics is considered. PMID- 1887705 TI - [Nucleic acid molecular hybridization as a method for the laboratory diagnosis of influenza: its potentials and prospects]. AB - Experiments carried out by the present moment in a number of laboratories indicate that the method of molecular hybridization (MH) has great diagnostic potential. Sufficient methodological mastery of the reaction of radioactively labeled DNA probes with RNA samples applied into a polymer membrane and good supply of commercially available materials make it possible to recommend this method for use in reference laboratories at specialized diagnostic centers. Hybridization should be used in combination with traditional virological and serological tests; the combined use of MH and the enzyme immunoassay for the determination of viral antigens permits the documentation of 90-98% of all cases of influenza A with sufficient rapidity. In the near future DNA probes for the diagnosis of influenza B and C are likely to appear. MH has rather good prospects for the analysis of experimental infection in laboratory animals, as well as for the study of the replication of influenza virus in all cultures. The prospects of the study of the processes of expression of individual genes seem to be particularly attractive. MH may play an important role as a tool for documenting vaccinal reaction, as well as for the study of the action of different chemical preparations in volunteers. And finally, the greatest expectations are linked with the use of MH for the search of inapparent (persistent, latent, etc.) forms of influenza virus infection both in experimental systems and in humans. Optimistic prospects of the studies in this field are based on high sensitivity of this method combined with its equally high specificity. An additional reserve for enhancing sensitivity is also present here due to the amplification of target molecules. PMID- 1887706 TI - [The 7th cholera pandemic in the world and the USSR]. AB - 1,713,057 cases of cholera were registered in the world during the seventh pandemic of the disease at the period of 1961-1989. The pandemic still continues, being the most prolonged pandemic in comparison with earlier ones. During the period of the seventh pandemic 10,723 cases of cholera were registered in the USSR. Great outbreaks occurred in 1965 and 1970-1974. At present sporadic cases of cholera can be registered, and wide circulation of mainly avirulent, nontoxigenic strains of cholera vibrios in environmental objects is characteristic of the epidemic situation. PMID- 1887707 TI - [The effect of new antimicrobial preparations used in combination with complete gnotobiotic isolation on the survivability and intestinal microflora of total body irradiated mice]. AB - The aim of these investigations was the study of the effect of different antimicrobial preparations on the survival rate and intestinal microflora of mice with experimental acute radiation sickness. These investigations revealed that the survival rate of the animals increased 3.1 times with the use of Supramycin, 2.4 times with the use of Tacef and 1.6 times with the use of Spizef and Pen bristol. The study of the influence of these preparations on the intestinal microflora revealed that Spizef not only decreased the number of opportunistic microorganisms, but also led to a sharp drop in the level of lactobacteria. The use of Pen-bristol and Tacef led to practically complete elimination of enterobacteria enterococci, staphylococci, as well as lactobacteria. Supramycin essentially suppressed the number of opportunistic microorganisms and did not affect the level of lactobacteria. This was probably the cause of the highest effectiveness of Supramycin in comparison with Tacef, Spizef and Pen-bristol. PMID- 1887708 TI - [The practical performance of cholera control measures in the USSR during the 7th pandemic]. AB - The critical analysis of anticholera measures carried out in the USSR since 1965 till the present time is presented. The grounds for the abolition or considerable reduction of a number of measures are considered from the viewpoint of their scientific substantiation, the adequacy of means and efforts spent for their realization and their antiepidemic effectiveness. Special attention is paid to the necessity of differentiated approach to these measures, depending on concrete local climatic and geographical, sanitary, hygienic and other factors which determine the epidemic potential of a given administrative territory. PMID- 1887709 TI - [A gel filtration study of the fractional composition of tetanus antitoxic sera]. AB - The fraction composition of tetanus antitoxic sera has been studied by the method of gel filtration in columns packed with Sephadex G-200. Differences in the fraction composition of preparations manufactured by different enterprises have been revealed. The specific activity of antitoxic sera has been found to depend on the degree of their fragmentation. PMID- 1887710 TI - [The homogeneity of a population of production strain 205 of the tick-borne encephalitis virus]. AB - Tick-borne encephalitis virus strain 205 was characterized by such sign as the presence of negative colonies. In the swine fibroblast cell line the population of the strain was represented mainly by large plaque (67.3%). Medium-sized plaques prevailed in chick embryo fibroblast cell culture. Protamine sulfate and magnesium chloride reduced the period of incubation, increased the resolving capacity of the plaque method and the proportion of medium- and small-sized plaques. Agarose B rendered the virus colonies less contrasting. The production strain and the clones of its population were found to have pronounced reproductive and protective properties. The S+ variants of the virus exhibited the highest reproductiveness. PMID- 1887711 TI - [The mutagenicity of a new multicomponent vaccine made from the antigens of Klebsiella pneumoniae, Staphylococcus aureus, Proteus vulgaris and Escherichia coli]. AB - Inactivated bacterial vaccine, containing K. pneumoniae, S. aureus, P. vulgaris and E. coli antigenic complexes were tested for mutagenicity in the test described by Ames et al. and in vivo, in experiments on mice. In Salmonella typhimurium cells, strain TA-98 and TA-100, the preparation (5-75 mg/ml) did not increase the frequency of reversions and histidine-independence either in direct experiments or after metabolic activation with rat liver homogenate. In experiments on mice the vaccine (3.3 mg/kg and 33 mg/kg) did not induce chromosomal anomalies in spermatogonia. In all experiments the mutagens used for positive control produced a mutagenic effect. PMID- 1887712 TI - [The immunomodulating action of the surface antigens of the influenza A virus in experimental staphylococcal infection]. AB - The results of the study of influenza A virus surface antigens, hemagglutinin and neuraminidase, in the induction of nonspecific immunomodulation and protection from acute pulmonary staphylococcal infection have been studied. Protective effect, the cell composition of bronchoalveolar lavage fluid depend on the serological subtypes of surface antigens used for intranasal immunization and the infective dose of staphylococci. PMID- 1887713 TI - [The determination in saliva of IgA antibodies to Shigella ribosomes for the diagnosis of dysentery]. AB - The levels of antiribosomal antibodies to Shigella ribosomes in serum and saliva samples from 38 dysentery patients (15 S. sonnei cases and 23 S. flexneri cases), 14 patients with salmonellosis and 136 healthy adults were determined in ELISA with ribosomes from S. sonnei R-mutant used as solid-phase antigen. High levels of "normal" antiribosomal IgA, IgG and IgM antibodies were revealed in the sera of healthy persons while the level of salivary IgA antibodies was very low. In dysentery infection no increase in the levels of serum IgG and IgM antibodies and only a slight increase in the level of IgA antibodies were revealed. Local immune response was manifested by the early (on days 2-4 from the onset of infection) and significant augmentation (12- to 16-fold) of salivary antiribosomal IgA antibodies. An increase in the level of these antibodies was registered in 95 100% of dysentery patients but not in patients with salmonellosis, which made it possible to recommend the method for diagnosing shigellosis. Immune response to Shigella ribosomal antigens, in contrast to the response induced by Shigella O antigen, is almost exclusively local. PMID- 1887714 TI - [The effect of chemical preparations on the biological properties of the intestinal lactobacilli in experimental animals]. AB - The oral administration of the therapeutic doses of tetracycline, pefloxacin, ampicillin, cephalexin, rifampicin, sisomicin to Wistar rats for 5 days was accompanied by a decrease in the total number of lactobacilli in feces and by changes of the species spectre of these microorganisms. In those rats species, never found in intact animals, could be revealed rather frequently. All antimicrobial preparations administered in this investigation induced a decrease in the proportion of antibiotic-sensitive cultures and led to the selection of strains having multiresistance and increased antagonistic activity with respect to Pseudomonas indicator strain. The possible relationship between the markers antibiotic resistance and antagonistic activity in lactobacilli is discussed. PMID- 1887715 TI - [The production and characteristics of liposomes bearing interferon antibodies on their surfaces]. AB - Liposomes carrying anti-interferon antibodies 5A6 on their surface were prepared from the mixture of lecithin and cholesterol. The binding of antibodies with the liposomal membrane was achieved by their modification with palmitic acid molecules in an amount of 3-4 molecules per vesicle. Antibodies on the liposomal surface were shown to retain their antigenic specificity, but the amount of the antigen bound by them was less than a half of the possible maximum amount. Double immune complexes could be formed on bound antibodies, but the number of such complexes was relatively small. The causes of a decrease in the sorption of interferon and the formation of immune complexes are discussed. PMID- 1887716 TI - [Changes in the lymphocyte membrane lipids during immunization and staphylococcal infection]. AB - The relationship between the state of the lipid complex of lymphocyte membranes and their functional activity has been studied in normal mice after immunization and in mice with staphylococcal infection. The study has revealed essential differences in the dynamics of free-radical processes under normal conditions and in the presence of pathology, as well as their relationship to changes in the functional state of lymphocytes and, in particular, to the development of immunodeficiency. PMID- 1887717 TI - [An immunomorphological study of the lymphoid organs in the experimental administration of virulent and avirulent Shigella flexneri 2A strains]. PMID- 1887718 TI - [The limitation and inhibition of microorganism viability by metal ions]. PMID- 1887719 TI - [An exhibition in the Central Museum of Medicine of the Academy of Medical Sciences of the USSR dedicated to the centenary of the birth of Academician P. F. Zdrodovskii]. PMID- 1887720 TI - [A comparative study of 2 substances produced by the Streptococcus sp. Thom-1606 strain]. AB - Among the substances secreted by Streptococcus sp. Thom-1606 [correction of TOM 1606], two substances exhibiting opposite biological action have been detected. Their antigenic structure, as indicated by the data of immunoprecipitation in agar, are not identical. The compounds contained in the substance with antibacterial action have molecular weight below 10 KD, Stokes' radium equal to 1.10 +/- 0.15 nm and electrophoretic mobility approximating that of d1-fraction of human blood serum. The compounds contained in the substance inhibiting the antibacterial activity of the preparation have molecular weight within the range 70-100 KD, Stokes' radius equal to 3.52 +/- 0.25 nm and electrophoretic mobility approximating to that of gamma-globulin of human blood serum. The removal of the inhibiting substance by ultrafiltration and chromatographic techniques enhanced the antibacterial activity of the commercial preparation tomicide. PMID- 1887721 TI - Numbers of axons innervating mystacial vibrissa follicles in newborn and adult rats. AB - Electron-microscopic techniques were used to determine the numbers of axons in the deep vibrissal nerves innervating the C1 and C4 follicles in newborn and adult rats. All counts were made from thin sections taken after the nerve had entered the follicle capsule (FC). In newborn animals, the nerves supplying the C1 (n = 10) and C4 (n = 10) follicles contained an average (means +/- standard deviation) of 355.0 +/- 40.0 and 233.9 +/- 19.2 axons, respectively. In the adult animals (n = 10 for C1 and n = 9 for C4), the respective values were 314.4 +/- 26.2 and 233.3 +/- 34.4 axons. There were no significant differences between the values for the counts from the neonates and adults for either follicle (p greater than 0.01, independent t tests). In the vibrissal nerves of neonates, both degenerating axons and occasional growth cones were visible. Such profiles were not observed in the nerves taken from adults. PMID- 1887722 TI - Functional asymmetries in the rodent barrel cortex. AB - Neurophysiological and 2-deoxyglucose (2DG) studies of the rodent whisker barrel cortex have demonstrated asymmetries in its functional organization. To examine the possibility that the activity gradients observed in metabolic studies can be attributed to subtle rostral-caudal and dorsal-ventral asymmetries in electrophysiologically measured surround or cross-whisker inhibition, we compared 2DG results with predictions generated from quantitative single-cell receptive field data. Despite differences in the two experimental approaches, there is remarkable agreement between the findings. (1) The distribution of 2DG activity declines across the barrel cortex of the behaving animal from anteromedial barrels to posterolateral barrels, and is qualitatively and quantitatively similar to the values predicted from neurophysiology. (2) The strength of surround inhibition in barrel neurons predicts the twofold increase in activation of the C3 barrel following acute clipping of adjacent whiskers. And (3) within a cortical column, the decrease in metabolic activity associated with adjacent whisker stimulation is greatest in layer IV and least in the infragranular layers; this corresponds to the laminar distribution of inhibitory interactions observed electrophysiologically. PMID- 1887723 TI - Cerebellar projections to the somatic pretectum in the cat. AB - Neurons in the somatic pretectum receive input from the dorsal column nuclei (DCN) and project to a comparable "somatic" portion of the dorsal accessory nucleus of the inferior olive (DAO). This somatic DAO is reciprocally connected with the anterior interpositus nucleus of the cerebellum. One question that arises is whether this circuitry is further controlled by an output specifically from the anterior interpositus nucleus to the somatic pretectum. Wheatgerm agglutinin conjugated to horseradish peroxidase was injected into various parts of the cat pretectum. Injection sites were interpreted as including the somatic pretectum if neurons in the DCN were retrogradely labeled and if anterograde terminal labeling occurred in somatic DAO. The locations of retrogradely labeled neurons within the deep cerebellar nuclei were then compared in cases in which the injection sites included or excluded the somatic pretectum. In all cases in which the injection site included the somatic pretectum, retrogradely labeled neurons were observed in the anterior interpositus nucleus as well as in the lateral cerebellar nuclei. In some of these cases, neurons in the posterior interpositus and medial nuclei were also labeled. In contrast, in cases in which the pretectal injection site was located outside or at the border of the somatic pretectum, retrogradely labeled neurons were observed only in the lateral, posterior interpositus, and medial nuclei. Thus, the somatic pretectum appears to receive input primarily from neurons in the anterior interpositus nucleus, along with some input from neurons in the lateral nucleus. These results provide additional evidence for a pathway through the DCN in which sequentially processed somatic information has access to and is modulated by cerebellar circuitry. The existence of such a pathway supports the conclusion that neurons in the DCN convey somatic information important not only for cutaneous, kinesthestic, and other bodily sensations, but also for the control of movement. PMID- 1887724 TI - Stimulus features relevant to the perception of sharpness and mechanically evoked cutaneous pain. AB - Mechanical probes of various sizes and shapes were used to determine thresholds for the perception of pressure, sharpness, and pain on the human finger. As force increased, perception changed from dull pressure to sharp pressure to sharp pain. With the smallest probe (0.01 mm2), sharpness threshold was very close to pressure threshold. As probe size increased, sharpness and pain threshold expressed in terms of force) increased in proportion to probe circumference (not probe area), whereas pressure threshold increased relatively little. Pain and sharpness thresholds also increased as probe angle became obtuse. There was a statistically significant increase in both thresholds with a probe angle change of 15 degrees. Thus, both size and shape are necessary to describe a mechanical stimulus adequately, and pressure (force/area) is not a sufficient metric for pain studies. Thresholds varied at different skin sites on the finger. The dorsal surface had lower thresholds than the volar surface, but the difference between the two areas was not always statistically significant. The compliance of the skin (e.g., the amount of indentation produced by a given force) exhibited no relation to sharpness or pain threshold, whether considered within subjects at various skin sites, or across subjects at the same skin site. Comparison of the perceptual thresholds with the thresholds for nociceptors determined in electrophysiological studies indicates that the sensation of nonpainful sharpness is likely to be mediated by nociceptors. Furthermore, considerably more than threshold activation of nociceptors is necessary for normal pain perception. PMID- 1887725 TI - The effects of cross-modal manipulations of attention on the detection of vibrotactile stimuli in humans. AB - Although it is well known that attention to a visual or auditory stimulus can enhance its perception, less is known concerning the effects of attention on the perception of natural tactile stimuli. The present study was conducted to examine the magnitude of the effect of cross-modal manipulations of attention in human subjects on the detection of weak, low-frequency vibrotactile stimuli delivered to the glabrous skin of the finger pad of the right index finger via an Optacon. Three suprathreshold vibrotactile arrays (40 Hz), varying in the number of activated pegs and hence the area of skin stimulated, were used. Subjects were trained to detect the occurrence of vibrotactile or visual stimuli and to respond by pressing a foot pedal as quickly as possible thereafter. Two instructional lights were used to cue the subjects as to which stimulus modality they should attend, in three experimental conditions. In the first cue condition, the forthcoming stimulus modality was indicated by the illumination of its associated light. In the second cue condition, both instructional lights were illuminated, and the subjects were asked to divide their attention equally between the two modalities. In the third cue condition, the stimulus modality was falsely indicated by the illumination of the cue not associated with the stimulus to be presented. Reaction times (RTs) were calculated for each trial. For each modality, tactile and visual, the RTs varied significantly with the cue condition, with the mean RT changing in a graded manner across the experimental conditions (being shortest for the correctly cued condition, intermediate for the neutrally cued condition, and longest for the incorrectly cued condition.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1887726 TI - Electromyographic activity of mystacial pad musculature during whisking behavior in the rat. AB - Cinematographic measurements of whisker movements generated by behaving rats were compared with electromyographic (EMG) activity recorded simultaneously from mystacial pad musculature. Muscle activity consisted of repetitive bursts, each of which initiated a "whisking" cycle consisting of a protraction followed by a retraction. Protraction amplitude and velocity were directly proportional to the amount of EMG activity during forward whisker movement. Overtime, the intensity of muscle discharge determined the set point about which the vibrissae moved; higher levels of muscle activity resulted in a greater degree of overall whisker protraction. These findings are consistent with the known anatomy of the facial musculature and underscore the importance of whisker protraction in the acquisition of tactile information by the vibrissae. PMID- 1887727 TI - Trigeminal projections to contralateral dorsal horn originate in midline hairy skin. AB - The present study tested the hypothesis that the trigeminal (V) primary afferent projection to the contralateral dorsal horn originates in midline hairy skin. A prior study (Jacquin et al., 1990) showed that this crossed projection is heaviest to ophthalmic regions of medullary and cervical dorsal horns, and that it does not arise from V ganglion cells that innervate cornea, nasal mucosa, or cerebral dura mater. Here, retrograde double-labeling methods were used to show that many ophthalmic ganglion cells that innervate midline hairy skin via the supraorbital nerve project to the contralateral medullary and upper cervical dorsal horns. Diamidino yellow injections into the right dorsal horn labeled an average of 104 cells in the left V ganglion. Of these contralaterally projecting ganglion cells, an average of 45% were also labeled by horseradish peroxidase (HRP) injections into the left supraorbital nerve, and 25% were also labeled by HRP injections into the midline opthalmic hairy skin. However, only 2% were labeled by HRP injections restricted to left supraorbital vibrissae follicle nerves. Almost all of the double-labeled cells were located in the dorsal one half of the V ganglion, and they did not differ in size from single-labeled cells. On the basis of these and prior data, we conclude that a high percentage of contralaterally projecting V ganglion cells originate in midline hairy skin. It is also likely that the contralaterally projecting V ganglion cells serve a low-threshold mechanoreceptive function, given the relatively large ganglion cells and axons giving rise to this pathway and their central terminations in dorsal horn laminae III-V. PMID- 1887728 TI - Chronic functional consequences of adult infraorbital nerve transection for rat trigeminal subnucleus interpolaris. AB - In adult rats, transection of the infraorbital nerve and subsequent regeneration have been shown to result in altered somatotopic organization and changes in response properties of primary afferents within the trigeminal ganglion. The present study examined how these changes affect the postsynaptic targets of these neurons within subnucleus interpolaris of the trigeminal brainstem. Extracellular recordings were made from 330 cells in normal rats and 424 cells in rats surviving 57-290 days after transection of the infraorbital nerve in adulthood. Adult infraorbital nerve transection resulted in significant functional reorganization within subnucleus interpolaris. Relative to normal rats, the major changes can be summarized as follows: (1) a decrease in the dorsoventral extent of infraorbital representation; (2) a disruption of inter- and intradivisional somatotopic organization; (3) an increase in the proportion of cells with no discernible receptive field; (4) an increase in receptive field size for cells with infraorbital receptive field components; (5) the appearance of a significant proportion of cells with discontinuous receptive fields; (6) an increase in the proportion of cells exhibiting interdivisional convergence; (7) significant changes in the types of receptor surfaces activating local-circuit neurons with infraorbital receptive field components; (8) the appearance of a significant proportion of cells exhibiting convergence of different receptor surfaces; (9) significant changes in the dynamic response characteristics of cells with infraorbital receptive field components; and (10) an increase in the proportion of spontaneously active infraorbital-responsive cells. The changes observed were quite similar to those reported in adult subnucleus interpolaris following neonatal infraorbital nerve transection. The majority of changes observed in both studies can be most parsimoniously explained by alterations of primary afferents. However, central mechanisms may be more likely substrates for others. Regardless of the mechanism, the mature rodent trigeminal system appears capable of considerable functional reorganization following peripheral nerve damage. PMID- 1887729 TI - The location of spinothalamic axons within spinal cord white matter in cat and squirrel monkey. AB - The locations of spinothalamic (STT) fibers in the spinal cord white matter have been identified in cat and squirrel monkey by light-microscopic visualization of labeled fibers following multiple thalamic injections of wheatgerm agglutinin conjugated to horseradish peroxidase. Thalamic injections were combined with either a constricting dural tie or an intraspinal injection of colchicine to facilitate axonal labeling at more rostral spinal levels. In the cat, the ventral to-dorsal distribution of labeled STT fibers was bimodal. In the ventrolateral white matter, labeled axons were coarse in nature and were primarily concentrated peripherally. In the dorsolateral white matter, labeled STT axons consisted of fine-caliber fibers concentrated in the ventral portion of the dorsolateral funiculus and were equally distributed throughout the medial and lateral white matter. In the squirrel monkey, the distribution of STT fibers was unimodal, extending from the ventral surface of the spinal white matter to the ventralmost portion of the dorsolateral funiculus. As in the cat, however, the ventrally located axons were large and coarse and were primarily located in the peripheral white matter, whereas the dorsalmost STT fibers were of fine caliber and were distributed equally in the medial and lateral white matter. PMID- 1887730 TI - [Experimental study on a new non constrained total shoulder prosthesis]. AB - We designed a new non constrained total shoulder prosthesis and examined it biomechanically. In order to adapt the shoulder prosthesis for the Japanese, fifty skeletal and one hundred radiographs shoulder joints of Japanese were measured. In radiographs we also measured curvature radius of the humeral head and glenoid fossa. We studied force analysis to elucidate the stability of gleno humeral joint using Rigid Body Spring Model. The result on this study indicate that to lengthen the glenoid surface and to make it near the same radius head and glenoid the joint stability will become stable. Our total shoulder prosthesis consist of a cobalt alloy humeral component, a cobalt alloy glenoid component and a high density polyethylene++ outer head put over a small head of humeral component. The glenoid component have two variations. One is for anatomical replacement and its central angle is 78 degrees. The other is for poor function of rotator cuff and its central angle is 110 degrees. The results of biomechanical experiments showed possibility and advantages of our non constrained total shoulder prosthesis being put into clinical practice. PMID- 1887731 TI - A human skeletal remain of the Kofun period excavated from the Shimozuru tumulus, Fukuoka Prefecture. AB - A human skeletal remain of the Kofun period were excavated from North Kyushu where human skeletons of the Yayoi period with a high face and tall stature had been found. The Shimozuru Kofun skull has a high upper face, the orbit and nasal part are close to the Yayoi skeletons excavated in this area, and those heights are higher than the mean values of the Yayoi skeletons in North Kyushu. PMID- 1887732 TI - [Diagnosis of cerebrovascular disorders using nuclear magnetic resonance tomography]. AB - Regarding cerebrovascular diseases magnetic resonance imaging (MRI) provides informations which could not be obtained before by any other imaging method. MRI permits an early detection of ischemic infarctions, exact delineation of lesions near to skull base, and microangiopathy. Further diagnosis of arteriovenous malformations and venous thromboses can be done without using contrast media. Exclusion of acute hemorrhage or subarachnoidal hemorrhage is still a domain of computed tomography (CT). Other MR methods, like magnetic resonance angiography (MRA) and magnetic resonance spectroscopy (MRS) are expected to replace angiography and positron emission tomography (PET) in the near future, at least for some purposes. PMID- 1887733 TI - [Cerebrovascular disorders--clinical aspects and follow-up]. AB - The observation of the spontaneous course of the extracranial vascular process as a characteristic cause of cerebral ischemia has shown that vascular changes occur largely independently from the appearance of cerebral functional disturbances in the associated vascular territory. Hemodynamic factors play a minor role; while with the present standard methods available, embolic mechanisms can be insufficiently analyzed. The prospective developmental observations of morphologic and fluid-dynamic aspects and supplemental cell biology and metabolic analysis provide new criteria for an individual risk evaluation of the various mechanisms causing pathologically different cerebral function disturbances, and their analysis has crucial significance for a therapy plan. PMID- 1887734 TI - [Prevention of cerebrovascular disorders]. AB - The decision for the optimal preventive and therapeutic interventions in cerebrovascular disease depends on the underlying disease process. Therefore it is important to identify the different pathomechanisms by modern techniques. The significantly increased cardiovascular risk of patients with atherosclerotic extracranial arterial disease--even when neurologically asymptomatic--makes identification and elimination of all vascular risk factors of crucial importance for primary and secondary prevention. The low risk of stroke without prior transient ischemic attacks makes prophylactic carotid surgery not advisable in asymptomatic patients. Regular controls by sonography are necessary to identify patients with progression of carotid stenosis, and the patients should be informed about warning symptoms of threatening stroke. Secondary prevention with antiplatelet agents (aspirin, ticlopidine) proved effective in patients with cerebrovascular diseases by significant reduction in mortality and in the incidence of stroke and myocardial infarction. The optimum dose of aspirin is not known. Patients with atherosclerotic lesions of the major cerebral arteries have not been shown convincingly to benefit from long-term anticoagulation, while the risk of bleeding complications is increased significantly. Major clinical trials have been initiated to evaluate the benefit of carotid endarterectomy. Anticoagulation therapy can reduce the risk of cardiogenic emboli. Recently it was demonstrated that also aspirin seems effective in reducing incidence of thromboembolic complications in patients with chronic atrial fibrillation. The start of anticoagulant therapy after cerebral embolism depends mainly on CT scan findings. PMID- 1887735 TI - [Cerebrovascular disorders as a manifestation of a generalized disease]. AB - During the last years several risk factors for cerebrovascular disease (CVI) could be identified by epidemiologic studies; the incidence of CVI, like that of coronary artery disease, seems to be closely related to high blood pressure, hyperlipidaemia, smoking and diabetes mellitus. The diagnostic difficulties in CVI, especially concerning the localization and size of vascular lesions, explain controversal results in the evaluation of different clinical studies. A comparison of these results is often hard to perform also out of the different statistical methods applied in the various trials. The development of improved diagnostic methods, especially ultrasonography, which allow a better definition of disease processes, offers an advantage for controlled screening and intervention trials. After all further improvements in disease prevention as well as in diagnostic and therapeutic procedures require an intensive co-operation between internal medicine and neurology. PMID- 1887736 TI - [The status of carotid artery surgery today: technique, indications, results]. AB - Carotid artery endarterectomy (CAE) is a surgical standard procedure today. The indication is the symptomatic patient (Stage II) with transient ischemic attacks (TIA) and stenosis of the internal carotid artery (ACI). Data of several studies have yielded a highly restrictive policy toward operative procedures in asymptomatic patients (Stage I) with carotid bruit or ACI-stenosis. Furthermore there emerged wide consensus, that patients with frank stroke (Stage III) should not be operated upon. As diagnostic procedures highly advanced non invasive procedures came up during the last decade, as well as computerized tomography and digital subtraction angiography. The operative procedure is performed in general anesthesia with controlled hypertension during the clamping period (n = 650). Perioperative results without using a shunt are not different to those with a shunt. During the last 5 year period our results yielded a 1% perioperative central permanent neurological deficit rate (CPNDR) and a 1% operative mortality. During a 51 months median observation period 1.5% presented again with transient ischemic attacks-with TIA; 0.6% developed a stroke and 2.2% deceased by cerebral complications yielding at totally 4.3% long term complication rate. The annual rates are 0.3%, 0.1% respectively 0.5%, totally 0.9%. In conclusion CAE can be offered as a safe surgical stroke preventing procedure in symptomatic TIA patients with ACI stenoses in our institution. Perioperative as well as long term results are yielding a high standard and are clearly better than those without operation. PMID- 1887737 TI - Effects of thiopental and halothane on spontaneous contractile activity induced in isolated ventricular muscles of the rabbit. AB - To see if the known properties of thiopental of reducing Ca2+ and K+ fluxes across the myocardial sarcolemma account for its arrhythmogenic action, we have evaluated the effect of the anesthetic on spontaneous contractile activity induced in isolated rabbit papillary muscles. Thiopental (20 mg/l) prolonged the duration of sustained automaticity induced by stimulation at 1-2 Hz in the presence of 1 mumol/l isoproterenol. Thiopental (10, 20 mg/l) shortened the delay before the onset of Ba(2+)-induced automaticity, which involves a decrease in a K+ current. The minimum concentration of Ba2+ required to induce automaticity was lowered by thiopental. Whether spontaneous activities were induced by high frequency stimulation in the presence of isoproterenol or by Ba2+, thiopental lowered the frequency of spontaneous beats. Thus, thiopental appears to have both arrhythmogenic and antiarrhythmic actions, and the former may be unmasked when catecholamines counteract the latter by increasing Ca2+ influx. Like thiopental, halothane (1.0%) decreased the frequency and force of Ba(2+)-induced automatic beats but, unlike thiopental, prolonged the delay before the onset of Ba(2+) induced automaticity, indicating that halothane acts as a purely antiarrhythmic agent in this type of automaticity. PMID- 1887738 TI - Malignant hyperthermia: an altered phospholipid and fatty acid composition in muscle membranes. AB - There is thought to be a genetic defect within the calcium release channel of the sarcoplasmic reticulum in malignant hyperthermia (MH). This primary alteration is hypothesized to influence the function and/or structure of various muscle membrane systems; e.g., to have a direct effect on the composition of the lipid matrix. Therefore, in striated muscle samples, we determined the quantity and fatty acid composition of the various types of membrane phospholipids. German Landrace pigs were classified as normal or susceptible to MH. Total lipid content from longissimus dorsi, semi-membranosus muscle, and heart left ventricular (HLV) samples were extracted with chloroform/methanol and subsequently separated by high performance liquid chromatography. The single phospholipid fractions were collected and, following derivatization, the quantities of individual fatty acids were determined using a capillary gas chromatographic method. In general, samples from the susceptible pigs contained lower absolute amounts of individual phospholipids. The most notable differences occurred in the HLV, where phosphatidylinositol, phosphatidylserine, phosphatidylethanolamine and sphingomyelin were all significantly less (P less than or equal to 0.05). The muscle from the susceptible animals also contained decreased amounts of the polyunsaturated phospholipid-bound fatty acids (P less than or equal to 0.05). These differences in phospholipid and fatty acid concentrations of membranes isolated from swine susceptible to MH may relate to their apparently increased sensitivities to halothane (e.g., fluidizing effects) or elevated temperature. PMID- 1887739 TI - Expired-breath ethanol measurement in chronic obstructive pulmonary disease: implications for transurethral surgery. AB - If ethanol is added to the irrigant used during transurethral prostatic resection, the absorption of fluid can immediately be detected by measuring the ethanol concentration in the expired breath. To evaluate this method further, we studied the influence of chronic obstructive pulmonary disease (COPD) on the agreement between expired-breath and blood-ethanol concentrations. In 14 men with a mean age of 62 years (range 55-68), the concentrations of ethanol in whole blood and end-expired breath were measured at 12 exactly timed intervals before, during, and after an intravenous infusion of 0.6 g.kg-1 ethanol for 60 min. The pulmonary function was normal in seven of the subjects (control group) whereas the other seven suffered from severe COPD (study group). The results show that the accuracy and precision of breath-alcohol analysis to predict the blood ethanol level were poorer during the infusion of ethanol than afterwards. However, at all times of sampling the estimation of blood-ethanol concentration indirectly by analysis of breath was not significantly different for COPD patients and the control group. We conclude that ethanol monitoring of irrigant absorption can be used successfully in patients with COPD. PMID- 1887740 TI - Hypoalgesia following intrathecal morphine: a segmental dependent effect. AB - The onset phase of hypoalgesia, following intrathecal morphine, was assessed by experimental argon laser-induced pain. A dose of 0.4 mg morphine was injected pre operatively at the L3-L4 level into nine patients. The thresholds to laser induced pain and pain-evoked brain potentials were monitored for 2 h at the S1, L1, and C7 dermatomes. Hypoalgesia was detected at the S1 and L1 dermatomes after 5 and 15 min, respectively. No hypoalgesic effect was found at C7. This indicates that hypoalgesia was caused predominantly by segmental spinal mechanisms during the onset phase, and not by a general widespread effect. No latency changes (conduction delay) of the brain potentials evoked from the hypoalgesic dermatomes were found. Cutaneous pain, induced experimentally by laser stimulation, has the advantage of being quantitative and is useful to assess the onset and the segmental spread of hypoalgesia. PMID- 1887741 TI - Failure to demonstrate unconscious perception during balanced anaesthesia by postoperative motor response. AB - Eighty patients undergoing a standardized balanced anaesthesia were randomly assigned to either a suggestion group (N = 38) or a control group (N = 42), in a double-blind design. Anaesthesia was maintained with nitrous oxide, enflurane and fentanyl. Patients in the suggestion group were played seaside sounds, interrupted by statements of the importance of touching the ear during a postoperative visit, by means of a prerecorded audiotape and headphones. Tapes containing these suggestions were played from 30 min after the first incision, for a duration of 15 min. Patients in the control group were only played seaside sounds. There were no significant differences between the groups in either the number of patients touching their ears postoperatively or the number and duration of ear touches. PMID- 1887742 TI - Variations in superficial renal cortical blood flow and tissue oxygenation: an experimental porcine model. AB - Renal cortical microcirculation and its relation to inulin clearance, central haemodynamics and pulmonary gas exchange were studied in eight pigs under continuous intravenous chlormethiazole-pancuronium anaesthesia. The animals were studied during six consecutive 30-min periods. Four of the animals were also studied 19 h after the first period. In the superficial renal cortex, regional blood flow (Qsrc) was measured by laser Doppler flowmetry (LDF) and tissue oxygenation (PtO2) by surface microelectrode technique. Central haemodynamics and pulmonary gas exchange values were distributed within normal ranges. The importance of stable central haemodynamics in order to perform accurate microcirculatory measurements in the renal cortex was documented. A significant relation between Qsrc and pulmonary capillary wedge pressure (PCWP) was found (P less than 0.0001) despite the fact that PCWP was distributed within a range of only 0.7 kPa (all values were well within the normal range for pigs). No other relationships were found between central haemodynamics or pulmonary gas exchange variables and renal microcirculatory parameters. Concerning renal microcirculation and inulin clearance, at least 2-3 h may be required for stabilization after surgery. The average temporal variability between measurements performed every 30 min in each animal was 6 +/- 7% (s.d.) in the LDF values and 21 +/- 21% in the PtO2 values (mean PtO2). No correlations were found between Qsrc or PtO2 and inulin clearance. Since the haemodynamic parameters, pulmonary gas exchange variables and haematocrit were distributed within narrow ranges, we regard the temporal microcirculatory variability obtained here as normal in this experimental situation, and consider the porcine model well suited for further studies concerning renal microcirculation. PMID- 1887743 TI - Model-based adaptive closed-loop feedback control of atracurium-induced neuromuscular blockade. AB - Closed-loop control of atracurium-induced neuromuscular blockade by a model-based adaptive feedback algorithm is described. Mean offsets (+/- s.d.) from setpoints at 50, 70 and 90% neuromuscular blocks using the Relaxograph were 1.1 +/- 1.3, 0.2 +/- 0.7 and 0.1 +/- 0.4%, respectively. Correspondingly, the mean steady state rates of infusion of atracurium were 0.20 +/- 0.06, 0.25 +/- 0.03 and 0.39 +/- 0.10 mg.kg-1.h-1. The described controller provides reasonable control of atracurium dosing at different degrees of neuromuscular blockade. It gives a solution to the problem of adapting pharmacokinetic and pharmacodynamic data to individuals when using population mean data as starting values for drug therapy. PMID- 1887744 TI - Effects of diltiazem on postischaemic renal cortical microcirculation in the pig. AB - Diltiazem--a calcium entry blocker--was tested in a porcine model under continuous chlormethiazole-pancuronium anaesthesia as protection against renal failure following 60 min of renal ischaemia. Fourteen pigs were randomly allocated to one experimental (diltiazem and ischaemia) and one control group (only ischaemia) (n = 7 in each). Diltiazem was administered as a continuous intravenous infusion started before the ischaemic insult. In two additional animals diltiazem was given but ischemia was not induced. The postischaemic renal cortical microcirculation was simultaneously investigated in four different regions in the left kidney during the first 4 h of reperfusion. Laser Doppler flowmetry (LDF) was performed in two different regions and measurement of tissue oxygenation was done in two other regions. In the two animals treated with diltiazem without ischaemia, only minor variations in central haemodynamic and renal microcirculatory parameters were evident. In the control group (ischaemia), superficial renal cortical blood flow (Qsrc) decreased from 49 +/- 11 (s.d.) arbitrary units at baseline to 24 +/- 4 arb. units 4 h after start of reperfusion (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1887745 TI - Hypoalgesia following epidural morphine: a controlled quantitative experimental study. AB - The efficacy, duration, and spread of epidural morphine hypoalgesia were assessed by an experimentally induced pricking pain evoked by laser stimulation. Four mg of plain morphine was injected epidurally in 7 volunteers at the L2-L3 interspace. Thresholds to warmth and pain perception, and pain-evoked potentials were measured. In the first experiment, hypoalgesia was monitored each hour for 7 h at various dermatomes. Hypoalgesia was detected at S1 dermatome after 2 h, but 3 h elapsed before hypoalgesia could be detected at the L1, T12, T10, T8, and T6 dermatomes. No effect was found at C7. No conduction delay was found along the pain pathway during hypoalgesia. Hypoalgesia lasted more than 7 h at S1, whereas hypoalgesia could not be detected after 5 h at other dermatomes. In the second experiment, naloxone (0.8 mg i.v.) was injected 230 min after injection of epidural morphine, and the subsequent recording 10 min later showed that hypoalgesia had been partly reversed. The onset and duration of hypoalgesia are different for experimentally induced pain and clinical pain. Experimentally laser induced pain has the advantage of being quantitative, and is, as such, useful to assess hypoalgesia, and to test the potency of narcotics. PMID- 1887746 TI - Effects of glycopyrrolate and atropine on heart rate variability. AB - Analysis of heart rate variability, combined with physiological tests (deep breathing and tilt tests) was used to characterise the effects of atropine and glycopyrrolate on the parasympathetic nervous tone of the heart in healthy male volunteers. The low dose of atropine (120 micrograms) administered as a continuous infusion in 15 min was associated with parasympatomimetic effects estimated by the slowing of the heart rate and an increase of the mean and beat to-beat heart rate variability. The bradycardia and increase of heart rate variability following infusion of glycopyrrolate (50 micrograms) was less marked and did not differ significantly from that of placebo. The higher doses of atropine (720 micrograms) and glycopyrrolate (300 micrograms) administered as a continuous infusion in 15 min produced an equal vagal cardiac blockade characterised by significant tachycardia and a decrease in overall and beat-to beat heart rate variability. It is concluded that at low doses the parasympatomimetic action of glycopyrrolate is less marked than that of atropine; and at higher doses only small differences exist between these two muscarinic antagonists in their effects on cardiac vagal outflow, assessed by heart rate and heart rate variability. PMID- 1887747 TI - Hemodynamic and catecholamine responses to laryngoscopy with vs. without endotracheal intubation. AB - To study the relationship between the intensity of the stimulus exerted against the base of the tongue during direct laryngoscopy and the magnitude of associated hemodynamic and catecholamine responses, a study was conducted in 40 ASA I or II patients. Laryngoscopy lasting 40 s was performed with a size 3 Macintosh blade connected to a force-displacement transducer. The intensity of the stimulus exerted during laryngoscopy is expressed by the product of its average force (N) and duration (s) and given as impulse in Ns. Highly significant relationships were found between the impulse during laryngoscopy and the maximal hemodynamic and catecholamine responses. Also, when laryngoscopy was followed by orotracheal intubation, significant relationships were found with steeper slopes of the regression lines for systolic blood pressure, heart rate and plasma epinephrine concentrations. A more rapid regression of hemodynamic data was seen in intubated patients, whereas their plasma catecholamine concentrations regressed more slowly. The mechanisms of the responses to laryngoscopy and orotracheal intubation are proposed to be by somato-visceral reflexes. Stimulation of proprioceptors at the base of the tongue during laryngoscopy induces impulse dependent increases of systemic blood pressure, heart rate and plasma catecholamine concentrations. Subsequent orotracheal intubation recruits additional receptors that elicit augmented hemodynamic and epinephrine responses as well as some vagal inhibition of the heart. PMID- 1887748 TI - The effect of positive end-expiratory pressure ventilation on atrial filling. AB - As a measure of atrial filling, left and right auricular diameter and free wall segment length were recorded by sonomicrometry during incremental positive end expiratory pressure (PEEP) in eight acutely instrumented closed chest dogs. The effect of PEEP was assessed with the pericardium open (n = 6) and closed (n = 8). On both occasions, PEEP decreased left auricular diameter (P less than 0.05). PEEP also caused a reduction in right auricular diameter with the pericardium open (P less than 0.05), while the variable was unchanged with the pericardium closed. PEEP did not cause any changes in either left or right free wall segment lengths. Both left and right auricular pressure-diameter relationships were progressively shifted leftwards with incremental PEEP. These observations suggest that PEEP may reduce left ventricular output not only by interfering with passive ventricular filling, but also by reducing atrial dimensions. PMID- 1887749 TI - Decreased expression of class II major histocompatibility complex (MHC) molecules on monocytes is found in open-heart surgery related immunosuppression. AB - The expression of class II major histocompatibility complex (MHC) molecules on monocytes and the relative proportion of immunoregulatory lymphocyte subpopulations were studied from the blood of eight patients undergoing a cardiac operation. The aim of the study was to reveal mechanisms responsible for depression of cellular immunity and B-lymphocyte activation associated with open heart surgery. A decreased staining of HLA-DR and even more of HLA-DQ class II MHC molecules was found on the monocyte surface in samples taken 2 and 7 days after operation when compared to preoperative values. The relative proportion of monocytes in mononuclear cells increased after surgery, but within lymphocyte subpopulations only a decrease in total T cells and an increased number of activated (HLA-DR positive) T cells were found, whereas the rations between various T cells subsets remained relatively stable. PMID- 1887750 TI - Effects of famotidine on gastric pH and residual volume in pediatric surgery. AB - Aspiration pneumonitis is a severe complication of anesthesia. The objectives of this study were to determine if preoperative famotidine, a new histamine2 receptor antagonist, given by mouth either the evening before or the morning of elective surgery, reduced gastric residual volume and increased gastric pH in pediatric patients. Either famotidine or placebo (or both) were orally administered to 58 children (aged 2-17 years). The patients were randomly assigned to four groups: Famotidine-Famotidine, Placebo-Placebo, Placebo Famotidine, and Famotidine-Placebo; subjects in the Famotidine-Famotidine group received two doses of famotidine (0.5 mg.kg-1 per dose), those in the Placebo Placebo group, two doses of placebo, those in the Placebo-Famotidine and Famotidine-Placebo group, one dose of each by mouth. The Famotidine-Famotidine group received one dose of famotidine at 22:00 the evening before surgery and a second dose 60-90 min before the scheduled time of surgery. The Placebo-Placebo group received two doses of placebo at the same times as the Famotidine Famotidine group. The Placebo-Famotidine group received a dose of placebo the night before surgery and a dose of famotidine the morning of surgery; the Famotidine-Placebo group received famotidine the night before surgery and placebo the morning of surgery. The administration of famotidine on the morning of surgery significantly increased gastric pH (4.8 vs. 1.3) in comparison with placebo, as did two doses of famotidine (6.6). Famotidine failed to reduce gastric residual volume significantly in any group. The administration of famotidine significantly reduced the number of pediatric patients considered at higher risk for aspiration pneumonitis, despite not decreasing gastric residual volume. PMID- 1887751 TI - Danger of metallic particles in the spinal-epidural spaces using the needle through-needle approach. PMID- 1887752 TI - Crawford W. Long--first amongst firsts, March 30th, 1842. PMID- 1887753 TI - Forty-six "first anaesthetics" in the world. PMID- 1887754 TI - Muscle relaxation rate in patients with malignant hyperthermia. PMID- 1887755 TI - Decreased glucose utilization in discrete brain regions of rat in thioacetamide induced hepatic encephalopathy as measured with [3H]-deoxyglucose. AB - To evaluate the possible contribution of bioenergetic failure in the particular brain regions to the pathomechanism of hepatic encephalopathy (HE), local cerebral metabolic rate for glucose (LCMRglue) was evaluated from [3H] deoxyglucose uptake in frontal, visual and auditory cortex, striatum, cerebellum and medulla oblongata of rats with acute HE induced with a hepatotoxin- thioacetamide (TAA). HE caused a decrease of LCMRglue in all the regions studied. The strongest decrease (about 65%) was noted in hippocampus and cerebral cortex- the two regions rich in glutamatergic neurons. The results indicate a possible link between decreased energy metabolism and impaired excitatory, glutamatergic neurotransmission--the two factors whose contribution to HE has so far been implicated separately. PMID- 1887756 TI - Marked reduction in CSF lactate and pyruvate levels after CoQ therapy in a patient with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke like episodes (MELAS). AB - Many CoQ trials for mitochondrial encephalomyopathy are reported, however, the action of CoQ in the central nervous system is unknown. We administered CoQ to a patient with MELAS, and decreasing CSF lactate and pyruvate levels were revealed. This reduction in CSF lactate and pyruvate may be evidence that CoQ acts directly on the CNS. There have been no other descriptions of evidence of CoQ effective action in the central nervous system, a finding unique to this report. PMID- 1887757 TI - Bone anomalies in myotonic dystrophy. AB - Sixteen patients with myotonic dystrophy underwent CT examination of the skull, and measurement of bone mineral density at lumbar spine and hip by dual-photon absortiometry. The results were compared with those of 20 normal subjects of similar age and sex distribution. Hyperostosis of the calvarium, and increased bone mineral density at lumbar vertebrae were observed. One case showed basal ganglia calcification associated with hyperparathyroidism secondary to deficiency of vitamin D. In the other 15 patients, studies of calcium metabolism were normal. There results suggest the existence of generalized hyperostotic potential in patients with myotonic dystrophy. PMID- 1887758 TI - Mode of action of triethylenetetramine dihydrochloride on copper metabolism in Wilson's disease. AB - The drug of choice for the initial treatment of "decoppering" in Wilson's disease, an inherited disorder of copper metabolism, is the chelating agent D penicillamine. In the case of harmful side-effects an alternative drug is triethylenetetramine dihydrocholoride (trien or trientine). Using the 24-h-urine excretion of copper and the oral copper loading test with copper-64, a double function for trien was found: trien increases the urine copper excretion and decreases the intestinal copper absorption respectively. PMID- 1887759 TI - HLA antigens in subacute sclerosing panencephalitis patients in Israel. AB - HLA Class I antigens were determined in the 49 subacute sclerosing panencephalitis (SSPE) patients. In analyzing the Arabs and the Jews separately, there is a decrease in HLA-A2 in the Jewish patients (X2 = 3.96; P less than 0.05), a significant increase in the HLA-A29 in the Arab SSPE patients (X2 = 6.29; P less than 0.02), and a slight, insignificant increase of HLA-A29 in the Jewish patients. The present study supports previous findings of Kurent's and needs following studies in larger groups of Arab SSPE patients. PMID- 1887760 TI - Neuropsychological deficits in asymptomatic carotid artery stenosis. AB - A total of 20 subjects with asymptomatic carotid artery stenosis (ACAS) and a group of healthy controls were compared as to their cognitive performance. Subjects with ACAS showed substantial deficits on tasks of mental speed, learning, visuospatial abilities, verbal processing and deductive reasoning. The cognitive profile of ACAS--subjects indicated non-specific impairment, possibly related to widespread cerebral vascular disease, of which the presence of ACAS may be one indicator. PMID- 1887761 TI - Familial narcolepsy in Finland. AB - Five patients with narcolepsy-cataplexy (aged 31-69, mean age at onset 15 years) and their 47 relatives were examined. They were interviewed in detail, all patients and 16 relatives (including all symptomatic cases) were examined neurologically and a multiple sleep latency test and HLA-typing were done. One case of narcolepsy and two cases of idiopathic hypersomnia were identified. All the other 45 relatives were symptom-free. The observed rate of familial cases (1/5 for narcolepsy and 2/5 for idiopathic hypersomnia) corresponds the results of other recent studies. PMID- 1887762 TI - Amyotrophic lateral sclerosis in Sweden in relation to occupation. AB - All cases of ALS in Sweden during the period 1970-1983, i.e., 1961 cases, were compared with an age-stratified random sample of 2245 individuals from the Swedish population. On the basis of census information, the male cases were found to be heterogeneously distributed over occupational groups. Significantly more male cases than expected were found among office workers (OR = 1.8; 34 cases) as well as among farm workers (OR = 1.7; 56 cases). There was a cluster of male cases in agricultural work in one south-western county (OR = 3.4; 25 cases). Significantly more female cases than expected were medical service workers (OR = 1.7; 33 cases). PMID- 1887763 TI - Serum antibodies to GM1 and GM3-gangliosides in systemic lupus erythematosus with chronic inflammatory demyelinating polyradiculoneuropathy. AB - Acute symmetric demyelinating polyneuropathy of the Guillain-Barre type is known in systemic lupus erythematosus (SLE). Chronic idiopathic demyelinating polyneuropathy (CIDP) has been reported rarely with SLE. A case is reported of CIDP accompanying SLE with autoantibodies against GM1- and GM3-gangliosides. There was no historical evidence to suggest SLE, and CIDP was the first manifestation of SLE. The 38-year-old patient had elevated CSF-protein, slow nerve conduction velocities, sural nerve biopsy revealed mixed axon loss with demyelination and CIDP white matter lesions were observed in magnetic resonance imaging, the GM1- and GM3-autoantibodies may play a role in the pathogenesis of CIDP in SLE. PMID- 1887764 TI - X-linked spastic paraplegia. AB - This paper describes a family with 10 males affected by x-linked spastic paraplegia. X-linked inheritance is rarely encountered in pure and complicated forms of hereditary spastic paraplegia. The disease was characterized by hyperreflexia, progressive spastic gait disorder, extensor plantar responses and mental retardation in all of the affected members of the family we studied. In addition to these symptoms, the older patients had cerebellar findings, severe disability and contractures. This is the 13th family manifesting x-linked spastic paraplegia reported in the literature. PMID- 1887765 TI - Febrile convulsions in northern Japan: a quantitative and qualitative analysis of EEG and clinical findings. AB - In an attempt to describe the characteristics of febrile convulsions (FC) 133 children with a history of FC were checked neurologically at health centers in northern Japan. Using categorical data from principal component analysis, family history of FC, recurrence and body temperature prior to convulsion, EEG disorders, exogenous factors, age at onset as the principal components were extracted. A quantitative and qualitative analysis of EEG showed that children with FC had more paroxysmal and basic abnormalities, that the rate of appearance of theta wave was more common and of alpha wave was less common, and that mean values of frequency ranges of theta and alpha wave ranges together were significantly lower in the background activity than those of control group children. PMID- 1887766 TI - A sensitive test to detect aprosody. PMID- 1887767 TI - Hypokalemic rhabdomyolysis in anorexia nervosa. PMID- 1887768 TI - Neurodegenerative diseases: basic and clinical research. The Tenth Sandbjerg Symposium. Sandbjerg, Denmark, June 10-12, 1990. Abstracts. PMID- 1887769 TI - Prognosis for obstructive sleep apnea after UPPP. PMID- 1887770 TI - Ocular rotation and perception of the horizontal under static tilt conditions in patients without labyrinthine function. AB - In a previous study (1) it was found that in healthy subjects Ocular (Counter) Rotation is mainly due to otolith stimulation and only to a minor extent induced by slanted visual structures. Stimulation of the neck by tilting the trunk laterally upwards did not result in a systematic rotation of the eyes. In the present study it was found that subjects with bilateral loss of vestibular function showed a higher visually induced ocular rotation. Tilting the head (cervical stimulation) or the whole body (somatosensory stimulation) also led to a considerable OCR, demonstrating substitution of other sensory modalities for the loss of vestibular function. Estimates of the subjective horizontal were noisy, demonstrating the lack of an adequate gravitational reference signal. PMID- 1887771 TI - Modelling the action of caloric stimulation of vestibule. III. Caloric nystagmus induced by osmotic pressure variation. AB - The properties of the membranous wall of the semi-circular canal and of the labyrinthine fluids give as a result the inflating pressure of this inflatable structure. The difference of osmotic pressure between perilymph and endolymph, which is involved in this problem, depends on temperature. Therefore, a caloric stimulation leads to a change in the inflating pressure. A numerical model, similar to the model used to study the effects of relative volume variations, gives a quantitative estimation of the transcupular pressure arising in a horizontal semi-circular canal (i.e. without gravity dependent effects) during a caloric stimulation, according to the inflating pressure change. As a consequence, it appears that rotational and caloric stimulations are not quite similar. The caloric stimulation leads not only to a transcupular pressure difference but also to a change in inflating pressure. As a result of the change in inflating pressure, the stiffness of the cupula varies. This modifies the gain and the dynamics of the vestibulo-ocular reflex, and may explain the asymmetry between hot and cold stimulations. PMID- 1887772 TI - Hearing decrease after loss of cerebrospinal fluid. A new hydrops model? AB - In a prospective study of 12 patients undergoing operation for acoustic neuromas the hearing on the contralateral ear was tested before and systematically day by day after operation. In 11 cases a perceptive loss of at least 20 dB was found at one or more frequencies during the first 2 postoperative weeks. A maximal average threshold decrease of 16.5 dB was found in the treble (2.4, 8 kHz average), while a tendency of a more pronounced decrease of 19.6 dB was seen in the low frequencies (125, 250, 500 Hz average). After 3 months the hearing had normalized in all cases. The explanation for the transitional loss supports the present theory: The loss of cerebro-spinal fluid during operation diminishes the CSF pressure. This decrease is transmitted to the perilymph via the cochlear aqueduct producing a transitory perilymphatic hypotonia, which in turn hydromechanically results in a relative endolymphatic hypertension mimicking an endolymphatic hydrops thus representing a human hydrops model. PMID- 1887773 TI - Intensity effect on latency and interval of human BAER. AB - Intensity effect on wave latency and interval (IPI) in brainstem auditory evoked responses (BAER) from birth to adulthood was investigated. The L-I functions were slightly steeper in younger groups than in older groups, which was associated with age-related difference in the absolute latencies. Wave I latency in most age groups exhibited two "transitional" responses: one at 70 dB HL or, sometimes, at 60 dB HL and the other mostly at 20 dB HL. As click intensity decreased, the I III IPI tended to decrease slightly while the III-V IPI tended to increase slightly in most age groups. Since the I-V IPI was constant at various intensities which could be attributed to a slight change in the morphology of wave III with altering intensity. PMID- 1887774 TI - ABR findings in vertebrobasilar ischemia. AB - Auditory brainstem response (ABR) changes in the ischemic brainstem condition and the correlation between ABR and blood flow of the auditory pathway are not clear. In this study, ABR changes in two cases with brainstem ischemia are reported. In order to clarify the correlation between ABR changes and cochlear blood flow, experimental studies on guinea pigs with brain ischemia were performed. Changes of ABR in the human brainstem ischemic condition consisted of a decrease of the amplitudes of all waves and a delay in wave latencies. Even if ABR showed no response, it turned to normal when the blood flow was recovered. In the experimental study, the same changing patterns in ABR occurred in parallel with a decrease of the cochlear blood flow, and the cochlear blood flow was not zero when ABR became non-responsive. This suggests that ABR changes reflect the degree of ischemia in the auditory pathway, and that non-responsive ABR does not imply irreversible ischemic condition. PMID- 1887775 TI - Acetylcholine receptor localization in human adult cochlear and vestibular hair cells. AB - The FITC technique using alpha-bungarotoxin visualized the staining pattern of acetylcholine (ACh) receptors in adult human cochlear and vestibular hair cells (HCs) in normal labyrinths and in cochleae with sensorineural hearing loss. Flourescence staining occurred in the cuticular plates of all HCs, indicating that the micromechanics of their suprastructures can act under cholinergic control. Quantitative differences of the fluorescence of ACh receptors occurred between the three rows of outer HCs at the same level in the cochlea and decreasing along a base-to-apex directed gradient. There is strong evidence that the subsurface cisterns are integrated in the efferent nerve system. In the degenerating organ of Corti an uncoupling of the efferent system takes places adjacent to disintegrating HCs, though the staining in the cuticular plates remains until a very late stage in HC disintegration. In vestibular HCs type I, fluorescence is emitted in the supranuclear area of the cytoplasm below the cuticular plate probably indicating an efferent guidance on the afferent nerve transmission directly via the HC itself. PMID- 1887776 TI - Ultrastructural changes in the outer hair cells of the guinea pig cochlea after exposure to quinine. AB - The outer hair cells have been shown to have motile properties which are likely to participate in the cochlear performance. Quinine is known to induce hearing loss as well as contraction of skeletal muscles. Isolated outer hair cells and isolated cochleae from guinea pigs have been exposed to quinine, which was also injected into living guinea pigs. When a physiological response was registered, the cells and cochleae were fixed and examined by transmission electron microscopy. In the isolated cells the formation of a central microtubule core occurred and in the cochleae a swelling of the subsurface cisternae in the outer hair cells was observed. The results are discussed in the context of a proposed effect of quinine on the contractile processes of the outer hair cells. PMID- 1887777 TI - Hyaluronan applied to lesioned round window membrane is free from cochlear ototoxicity. AB - Hyaluronan (HYA) in 1% solution was instilled into the round window (RW) niche of rats (n = 6) prior to perforating the round window membrane (RWM). Cochlear functioning and structure were then monitored by recording auditory brainstem responses (ABRs) at 2-31.5 kHz and by scanning electron microscopy. Perforation of the RWM alone (n = 6) resulted in immediate loss of ABR thresholds between 6 and 31.5 kHz in 2 of 6 animals. Similar results were obtained after instilling HYA into the RW niche and subsequent RWM perforation (n = 6). After 2 months, ABR thresholds were recorded at all frequencies in the HYA-treated animals, whereas in 2 of the controls no ABR thresholds could be elicited at 20 and 31.5 kHz. However, in both treatment groups the mean ABR thresholds and mean latencies for wave II at the ABR threshold returned to the pre-surgical (normal) range after 2 months. With respect to the cochlear morphology the results in both treatment groups were also alike including minor structural changes in hair cell stereociliae but no loss of hair cells. It is concluded that HYA, when instilled into the middle ear with the inner ear opened, is free from cochlear otoxicity. PMID- 1887778 TI - Quantitative histochemical study of secretory cells after short term tubal obstruction in the cat. AB - Quantitative histochemistry of goblet cells producing different types of glycoproteins was examined in cat middle ears with and without Euatachian tube obstruction (ETO). The goblet cell population significantly increased at 1 week after ETO and showed a tendency to decrease down to the normal level at 4 weeks after ETO. In the normal ears, approximately 85% of glycoprotein in the secretory cells were sulphated and 15% were neutral. ETO significantly increased goblet cell population containing sulphated glycoprotein at the expense of neutral glycoprotein. The results indicate that goblet cells can easily and within a short period be modified both in number and in intracellular glycoproteins by a tubal obstruction. PMID- 1887779 TI - Chronic suppurative otitis media: complicated versus uncomplicated disease. AB - To determine prognostic factors in patients with chronic otitis media who develop suppurative complications, we performed a retrospective study of all patients with chronic suppurative otitis media who underwent mastoid surgery between the years 1981 and 1989. Patients who developed complications were compared with those who did not with respect to six prognostic variables. The results indicated that patients with complications were younger (p less than 0.001), had shorter duration of ear discharge (p less than 0.001), were more likely to have pars tensa perforations (p less than 0.05), and had a higher degree of mastoid sclerosis in the operated and contralateral ears (p less than 0.001). The presence of cholesteatoma and the sex of the patient were of no prognostic value. Bacteriology of CSF and pus specimens from patients who developed intracranial complications mostly revealed mixed flora (62.9%). Proteus species was the most frequent isolate (34%) and anaerobes were present in 21.3% of specimens. Mastoid abscess occurred in more than half the patients in the complicated group. Brain abscess (57.4%) was the most frequent intracranial complication. On the basis of our findings we recommend that risk factors in patients with chronic suppurative otitis media be identified early to enable effective measures to be taken to eradicate the disease. PMID- 1887780 TI - Cholesteatoma in an Asian population. AB - Two hundred Malaysian patients representing 227 ears with previously untreated cholesteatoma disease were analysed retrospectively in terms of i) type of disease, i.e. primary acquired attic defect or posterior superior retraction pocket and secondary acquired type cholesteatoma; ii) positive history of previous middle ear effusion, atelectasis or grommet insertion; and iii) likelihood of complications as initial presenting feature. The high 47.1% incidence of secondary acquired cholesteatoma disease in our patients contrasts with the predominance of primary acquired cholesteatoma in the Caucasian patient. Correlation of these two disease types with a positive history showed a significant positive association between the primary acquired group and a positive history; and conversely a significant negative association for the secondary acquired type. This supports a role for the retraction theory in primary acquired cholesteatoma but negates this theory in secondary acquired cholesteatoma. Secondary acquired cholesteatoma had a significantly higher (35.5%) complication rate against 15.8% in the primary acquired type (p = 0.001). This fact together with a 47.1% incidence of secondary acquired disease, low otolaryngologist population ratio and patient attitudes to disease account for the high total complication rate of 27.3%. PMID- 1887781 TI - ELISA for determination of immunoreactive free elastase and elastase in complex with alpha 1-antitrypsin in nasal secretions with sinusitis. AB - Sensitive double antibody sandwich ELISA methods was developed in order to quantify immunoreactive neutrophil elastase (NE) levels in nasal secretions with chronic sinusitis (CS). Microwell plate as a solid phase was coated with anti-NE antibody. Two different horseradish peroxidase (HRP) labelled antibodies used as the second antibody were anti-NE-HRP for measuring total (free + complexed) NE level and anti-alpha 1-antitrypsin (AT)-HRP for complexed NE level. Mean value of total NE was 31.0 +/- 20.7 micrograms/ml in nasal secretions from adult patients with CS, and the percentage of complexed NE in total NE was 33.7 +/- 21.4%. This sandwich ELISA is a useful method for measuring both total and complexed NE levels in nasal secretions. PMID- 1887782 TI - Penetration of administered IgG into the maxillary sinus and long-term clinical effects of intravenous immunoglobulin replacement therapy on sinusitis in primary hypogammaglobulinaemia. AB - The influence of long-term intravenous immunoglobulin (i.v. IgG) replacement therapy on the clinical course of chronic sinusitis in patients with primary hypogammaglobulinaemia has not previously been reported. We have analysed the efficacy of i.v. IgG therapy and the penetration of administered i.v. IgG into the maxillary sinus. Seventeen patients with primary hypogammaglobulinaemia received i.v. IgG replacement therapy to maintain pre-infusion serum IgG concentrations above 4 g/l for periods of 12 to 58 (mean 36.7) months. Cases with established chronic sinusitis prior to therapy did not have symptomatic or radiological improvement at this dose, although no sinusitis developed de-novo in the 3 previously unaffected patients. The administered IgG penetrated into maxillary sinus antral lavage fluid in 3 patients from whom secretions were obtained at antroscopy. This indicates that poor clinical responses are not due to lack of penetration of antibodies to the required sites of action. Larger doses of i.v. IgG may be more effective in this situation, but the addition of antibiotics at high dosage may be a more economical therapeutic alternative. These findings highlight the importance of diagnosis of hypogammaglobulinaemia by measurement of serum IgG concentrations in patients who suffer from recurrent sinusitis, as the early institution of i.v. IgG therapy may prevent the development of sinusitis refractory to i.v. IgG therapy. PMID- 1887783 TI - Symptoms in heavy snorers with and without obstructive sleep apnea. AB - Five hundred and eighty persons who were heavy snorers filled in a questionnaire regarding symptoms on a 5-grade scale. Of these, 178 had a complete polysomnography investigation while 402 patients underwent oxymetric screening during the night only. On the basis of these investigations. 217 were classified as suffering from the obstructive sleep apnea syndrome (OSAS) and 363 as snorers without OSAS. The symptom scores differed between the two groups, but the range was wide and some persons with OSAS claimed only minor daytime sleepiness, somnolence, etc., while a high proportion of persons without OSAS frequently suffered from such symptoms. Thus, it was not possible to discriminate between patients with and without OSAS on the basis of their symptoms only. Furthermore, there are many persons who are "only" heavy snorers but who have symptoms that affect their career and social life and who so far have only received scant interest from the medical profession. Excessive daytime sleepiness and somnolence thus do not seem to be secondary to hypoxemia at night but rather to poor quality of sleep, which may be the case in association with heavy snoring even without appreciable deterioration of oxygen saturation. PMID- 1887784 TI - Long-time follow-up after UPPP for obstructive sleep apnea syndrome. Results of sleep apnea recordings and subjective evaluation 6 months and 2 years after surgery. AB - Fifty unselected consecutive patients with obstructive sleep apnea syndrome (OSAS) underwent uvulopalatopharyngoplasty (UPPP). The diagnosis was based on the patient's history and recording of respiration movements (Static Charge Sensitive Bed. SCSB) and oximetry, alone or combined with polysomnography. Renewed SCSB oximetry recordings were used to evaluate the success of the treatment. Six months postoperatively 40% of the patients were classified as non-responders, i.e. their oxygen desaturation indices (ODI) were reduced by less than 50% or were still above 20. The mean body mass index (BMI) was significantly higher in the non-responder group. A second recording with complete data was obtained in 45 patients after an average of 21 months. It was found that 9 patients who had been responders in the first postoperative recording had become non-responders. Only 18 of the patients with complete data could be verified as responders after 2 years. The patients who relapsed showed a significant increase in mean BMI between the first and second postoperative recordings compared to the patients who remained responders. There were no significant differences between responders and non-responders concerning age or preoperative severity of OSAS expressed as ODI, nadir SaO2 and percentage of obstructive periodic breathing. Of the non responders, 47% in the first postoperative recording and 52% in the second reported complete recovery from excessive daytime sleepiness. This subjective improvement was not correlated to the objective results. The conclusions of this study are thus that one postoperative recording is not enough to estimate the outcome of UPPP and that statements of the patient's subjective recovery alone must not be used for this purpose. PMID- 1887785 TI - The Waldeyer ring equivalent in the rat. A model for analysis of oronasopharyngeal immune responses. AB - By means of serial sectioning of the head and neck a paired, rod shaped, parachoanic lymphoid organ was identified in Lewis rats. Histological, ultrastructural studies and FACS analysis showed this organ to be a lympho epithelial organ with high endothelial venules (HEV) and a preponderance of B over T and T helper over T suppressor cells. Consequently this organ resembles the pharyngeal tonsil of man, and it is called the Waldeyer ring equivalent (WRE). The lymphatic drainage of this organ occurs predominantly to the deep, and to a lesser extent to the superficial cervical lymph nodes. Migration studies with 51Cr labeled cells show that the WRE lymphoid cells migrate into the lymphoid organs with HEV (peripheral lymph nodes. Peyer patches and WRE). In this respect they resemble peripheral lymph node cells more than cells from the Peyer patches. Thus the WRE lymphoid tissue in the rat is undoubtedly involved in local oronasopharyngeal immune surveillance and may also contribute to mucosal and systemic immune responses. PMID- 1887786 TI - Sialographic and ultrasonographic analyses of major salivary glands. AB - Seventy patients with major salivary gland diseases (60 parotis, 10 submandibular) were examined both with sialography and ultrasonography. The clinical and histopathological results were compared with radiological interpretations. Sialography was found to be 60% accurate for the diagnosis of salivary gland tumors and cysts and 63% for the diagnosis of inflammatory diseases. Ultrasonography diagnosed 95% of the tumors and 63% of inflammatory diseases accurately. PMID- 1887787 TI - Ultrastructural and histochemical study of the neuromuscular junctions in the denervated intrinsic laryngeal muscle of the cat. AB - Morphological changes and acetylcholinesterase (AchE) activity in the neuromuscular junctions (NMJ) of the normal and denervated posterior cricoarytenoid muscle (PCA muscle) of the cat were studied. Two days after denervation, the nerve terminals at the NMJ had almost disappeared. Six weeks after denervation, intensity of AchE activity at the former junctional site (FJS) was unchanged histochemically. At this stage, primary synaptic clefts were distorted and the Schwann's cells covered the FJS. Fourteen weeks after denervation, AchE activity at the FJS had decreased in contrast to that of the non-affected side. Calcitonin gene-related peptide (CGRP) was also investigated at the NMJ of the normal PCA muscles immunocytochemically. The present study shows that CGRP coexists with Ach in the nerve terminals of the PCA muscles and may be involved in the regulation of the contractile function of the intrinsic laryngeal muscle. PMID- 1887788 TI - [Pharmacokinetics of norethindrone-3-oxime and norethindrone in rhesus monkeys]. AB - After intravenous administration or nasal feeding of (6, 7-3H)-labelled norethindrone-3-oxime (NETO) or norethindrone (NET) to rhesus monkeys, the serum concentrations were determined by measuring the radioactivity after separation with HPLC. The serum concentrations of total extractable radioactivity were also measured without HPLC separation. In cases of nasal feeding, NETO and NET were quickly absorbed, and almost all of them were eliminated within 24 hours. NETO, when given via both routes, was partly metabolized to NET and partly remained in original form. The blood concentration--time curves for NETO and NET were adequately fitted to two compartment models. No significant difference in pharmacokinetic parameters between the two drugs was observed. The absolute bioavailability for NETO and NET were found to be 64.46 +/- 34.60% and 35.02 +/- 26.49% respectively. PMID- 1887789 TI - [Total synthesis of an analogue of schizandrin]. AB - A schizandrin analogue 9, 1, 2, 3, 10, 11, 12-hexamethoxy-6,7-dihydroxy-cis-6,7 dimethyl dibenzocyclooctadiene, is one of the metabolites of schizandrin with comparable anti-convulsion activity. In this paper, compound 9 was synthesized from gallic acid through the following sequence of reactions: methylation, Henry condensation, reduction with Fe-FeCl3-HCl, intermolecular reductive coupling and intramolecular nonphenolic oxidative coupling, totally in seven steps. The intermediate 1,4-diaryl-2,3-dimethyl-2,3-butanediol (7) which is a mixture of erythro and threo isomers was converted by DDQ in TFA into compound 9 and another new compound 10 via a different reaction path. PMID- 1887790 TI - [Synthesis of small peptides containing hydroxy-amino-acid, and its effects on progesterone production]. AB - Eleven peptides containing hydroxy-amino-acid have been synthesized manually by stepwise solid-phase method. Three of them were started on BHA-resin, the others on Merrifield-resin. TFMSA/TFA/p-cresol were used as cleaving reagent in all peptide-resin (1-11) cleavage. Furthermore, HF cleaving procedure was also used parallelly to five of those peptide-resins for contrast. No conspicuous difference in yield was found between TFMSA and HF. The purity of all products was checked by the profiles of analytical reversed phase HPLC (C-18) and the data of amino acid analysis. All synthetic peptides were tested for the effect on progesterone production by rat corpus luteum in vitro. Among them, three peptides, GlyTyr-NH2, LysTyr-NH2 and GlySer Lys-OH, showed significant effect (p less than 0.01) on inhibiting hCG-induced progesterone production. PMID- 1887791 TI - [Studies on the chemical constitutents of the traditional Chinese medicine "yun qian-hu" (Peucedanum rubricaule Shan et Shch.)]. AB - A new coumarin-glycoside and twelve known coumarins together with seven other known compounds have been isolated from the roots of Peucedanum rubricaule Shan et Shch. (Umbelliferae). The new coumarin-glycoside named rubricauloside, has been elucidated as 5,7-dimethoxy-8-[2'-hydroxy-3'-methyl, 3'-O-beta-d- apiofuranosyl(1----6)-beta-D-glucopyranosyl-butyl]-courmarin by means of spectral and chemical analysis. PMID- 1887792 TI - [Studies on the chemical constituents from the roots of Lamiophlomis rotata (Benth.) Kudo, a medical plant in Xi-Zang (Tibet)]. AB - Two new highly oxygenated iridoids, named lamiophlomiol A and B, were isolated from an alcohol extract of the roots of Lamiophlomis rotata (Labiatea) by silica gel G column chromatography. Lamiophlomiol A and B are two epimers. Their structures were elucidated to be Ia and Ib with spectroscopic and chemical analysis. PMID- 1887793 TI - [Studies on the chemical constituents of Flemingia philippinensis]. AB - Two new prenylated flavonoids, flemiphilippinin C (I) and flemiphilippinin D (II) have been isolated from the root of Flemingia philippinensis (Merr. et Rolfe) Li along with four known compounds. The structure of I and II were elucidated as 7 (.4'-hydroxy-3'-methoxyphenyl)-5-hydroxy-2, 2-dimethyl-10-prenyl-2H,6H-benzo-[1,2 b:5,4-b']dipyran-6-one and 5,7,2',4'-tetrahydroxy-6,8-diprenylisoflavanone, respectively, on the basis of chemical and spectroscopic data. The four known compounds were identified as 5,7,3',4'-tetrahydroxy-6,8-diprenylsilflavone (III), flemichin D (IV), beta-sitosterol (VI) and lupeol (VII), and a mixture of n C22 C30 aliphatic acid (V). Compounds III and IV showed significant cytotoxic activities against P388 cell cultures. PMID- 1887794 TI - [Use of the Powell method to optimize the composition of HPLC mobile phase--the separation of ephedrine and pseudoephedrine]. AB - The isomers ephedrine and pseudoephedrine are difficult to be separated by HPLC. In this paper, the Powell method was successfully introduced to optimize the composition of mobile phase in HPLC. On a mu Bondapak C18 column (8-10 microns, 3.9 mm x 30 cm), KH2PO4 solution methanol mobile phase system was optimized for separating ephedrine and pseudoephedrine by the Powell method. The optimized composition of the mobile phase was found as: 0.01 mol/L KH2PO4 -MeOH = 94: 6 (V/V). The Powell method was carried out in a process illustrated by tables and figures and 0.95 peak separation function was achieved. PMID- 1887795 TI - [Separation and quantitative determination of three saponins in licorice root by high performance liquid chromatography]. AB - A new analytical method for the separation and simultaneous determination of three saponins in Licorice root by high performance liquid chromatography has been developed. The saponins, glycyrrhizic acid (S-I), uralsaponin B (S-II) and uralsaponin A (S-III) were separated and determined by use of the solvent system CH3CN-3% HOAc (H2O) (47:53) at 248 nm, and with gradient increasing flow rate, the operation can be completed in 20 min. This method is sensitive and acuate with good reproducibility. The contents of three saponins in Chinese Licorice roots derived from four Glycyrrhiza species were determined. PMID- 1887796 TI - [Studies on decomposition kinetics of thalidasine in aqueous solution]. AB - In this report, the decomposition kinetics of thalidasine (TD) in aqueous solution at pH 2.0-7.8, salt concentration 0-0.132 mol/L, temperature 50, 60, 70, 80 degrees C, and different oxygen concentrations were investigated. The decomposition rate constant of TD in aqueous solution were determined by fluorescence spectrophotometer. The results showed: the oxidation reaction contributed largely to the overall decomposition, the oxidation rate of TD was found to be chiefly dependent on the PH of the medium and presence of oxygen. When in excess oxygen, the reaction followed pseudo first-order kinetics with respect to TD concentration. The rate constant can be expressed as: [formula: see text]. No primary salt effect was observed at pH 7.2. PMID- 1887797 TI - Effects of platelet-activating factor antagonist SRI 63-441 on endotoxin-induced changes in rat mesenteric microcirculation. AB - Intravenous injection of E. coli endotoxin 30 mg/kg to rats resulted in a systemic hypotension and rapid decrease in mesenteric arteriolar blood flow velocity (MABFV). The mesenteric arterioles constricted within 3 min followed by a short period of vasodilation after endotoxin administration. Pretreatment with the platelet-activating factor receptor antagonist SRI 63-441 attenuated the endotoxin-induced systemic hypotension and the decrease in MABFV, and abolished the mesenteric vasodilation effect of endotoxin infusion. The results suggest that PAF may be a mediator of endotoxic shock. PMID- 1887798 TI - [The identification of ephedrine and its analogues in urine by gas chromatography]. AB - A sensitive and reliable method of analysis for ephedrine and its analogues was established by using GC and GC-MS. The columns used for both GC and GC-MS were HP 5, and the carrier gas was helium. NPD was used as the detector for GC. The urine sample was extracted with ether and submitted to GC. If positive, it was then submitted to GC-MS to identify its structure. The detection limits for ephedrine and its analogues are lower than 200 ng/ml urine. The recoveries are above 80%. PMID- 1887799 TI - [Determination of 3,3'-dichlorodibenzoyl peroxide impurity in 3-chloroperbenzoic acid]. AB - An ultraviolet spectrophotometric method has been developed for the determination of 3,3'-dichloro dibenzoyl peroxide impurity in 3-chloroperbenzoic acid, an important epoxidation agent in drug (especially steroid) syntheses. The method is based on the selective extraction of the main component by aqueous alkali from a chloroformic solution. The solution of the test substance (0.05-0.1 g in 50 ml chloroform) is extracted four times with 20 ml portions of 0.1 M aqueous sodium hydroxide and the absorbance of the resulting chloroformic solution in measured at 286 nm to calculate the content of 3,3'-dichloro dibenzoyl peroxide impurity. Beer's law is obeyed in the 0-10% impurity range. The A10/01 cm.value is 77.9 and the correlation coefficient of the regression equation was found to be 0.995. The relative standard deviation of the measurement in the case of 2% impurity was +/- 0.43%. PMID- 1887800 TI - [Drug technology of a parenteral preparation for trimethoprim monotherapy]. AB - The formulation of Trimetoprim (TBP) injection has been studied. Use of N-N' dimethylacetamide in nonaqueous medium, propylene glycol, N-beta-hydroxyethyl lactamide-propylene glycol and Macrogol--400 resulted in the preparation of the solution in appropriate concentration. In the presence of adequate quantity of ascorbic acid the TBP is soluble in 0.8% concentration. It was experimentally proved that the equimolar ratio is optimal for the TBP-ascorbic acid combination. After the preparation of the solution and lyophilized formulas the presence of TBP-ascorbic acid adduct has been proved by derivatographic and NMR spectroscopic techniques. It has been found that the lyophilized formula is stable without decomposition for six years. PMID- 1887801 TI - [Some criteria for the planning and evaluation of the ruggedness test of HPLC methods]. AB - Ruggedness is a measure of the reproducibility of the individual test results when the procedure is used repeatedly to determine the same homogeneous sample in a variety of specified experimental conditions. Ruggedness testing can be divided into two major groups: Type-A, when the influence of the changed environmental conditions (different equipment, analysts, etc.) on the analytical performance parameters and results are tested, and Type-B, when the effect of variation in the experimental conditions are checked. In the latter case, Type-B group can be further classified into two major subgroups: ruggedness testing of sample preparation and chromatographic separation. Checking sample preparation for ruggedness testing includes the investigation of various sample preparation procedures, such as: liquid-liquid extraction, solid phase extraction, direct sample introduction and derivative formation. The investigation of column-to column variability, changes in the instrumental and experimental conditions belongs to the ruggedness testing of chromatographic separation. In this paper the basic principles of selection for experimental variables for various ruggedness tests are discussed introducing a new possibility to design multivariable-multicriteria system, and the evaluation of a single-variable single-criterion system, as well. In general, from the work introduced in this paper, it can be concluded that when new analytical methods are developed, it is quite important to be aware the sensitivity of the method to variations in the specified conditions. For adequate performance of ruggedness testing: a) the factors (variables) which have significant influence on the chromatographic results can be firstly selected, b) maximum acceptable deviations from the prespecified experimental conditions can be decided, and c) the acceptable deviations from the values of the prespecified analytical performance parameters can be defined. PMID- 1887802 TI - [Analysis of steroids. Part 40. Isolation and identification of unusual impurities in ethynodiol diacetate]. AB - In the course of the estimation of the impurity profile of ethynodiol diacetate, in addition to common impurities such as norethisterone acetate, ethynodiol-3 acetate and alpha-ethynodiol diacetate, two unknown impurities were detected by analytical reversed phase HPLC (C-18 silica and 80% aq. methanol as the eluent) and isolated by normal phase preparative HPLC (silica and 98:2 mixture of hexane and 2-propanol as the eluent). The 1H- and 13C-NMR spectra of the isolated impurities revealed that their structures could be characterized as the E and Z isomers of an analogue of EDDA containing "trimerised acetyl" group at the 17 hydroxy group (structures 4 and 4a). These structures were in good agreement with the extended UV spectra of the impurities and the mass spectra with the m/z 438 peak which can be derived from 4 and 4a by the loss of ketene. PMID- 1887803 TI - [Constituents of Asarum europeum L. Communication No. 18. Dynamics of the synthesis of flavonoids]. AB - In the present study, the dynamics of the biogenesis of the flavonoid compounds in haselworth such as isorhamnetin and quercetin glycosides and chalcone diglycoside, respectively, were investigated at various ontogenetic stages. The yield of transisoasarone and chlorophyll a and b were also analysed. The high concentration of transisoasarone was found in the rootstock (rhizome). Flavonoids were accumulated in the leaves; some chalcone diglycoside was found in the rhizome, too. The maximum concentration of flavonoid glycosides was detected in spring. In this period the young leaves are not protected either by cover leaves of buds or by the foliage of the uppermost zone of the vegetation. At this stage the a possible function of flavonoid glycosides could be the protection of the assimilation apparatus of young leaves against UV radiation. PMID- 1887804 TI - [HPLC-investigations of imidazoquinazolone derivatives. Part 2]. AB - In a previous paper (2) authors, reported good correlation between the HPLC (log k') and TLC (RM) retention data and the 1-octanol/water partition coefficient (log l') of imidazoquinazolone derivatives synthetized in their laboratory. In the present work the behaviour of the compounds in HPLC systems containing ion pairing agents (camphorsulfonic acid, Na-dodecyl sulfate) has been studied. While, in reversed phase systems no change of retention indicating the formation of ion-pairs or molecule complexes was observed, camphor-sulfonic acid caused significant increase of retention in the chromatographic systems with bare silica as stationary phase. This phenomenon is interpreted by the formation of camphorsulfonic acid double layer on the silica surface and as a consequence of mixed retention mechanism. The results of a detailed study on the latter subject will be published in a next paper. Double peak formation was observed in reversed phase system in case of C1-C3 disubstituted derivatives. This was interpreted with the formation of isomeric mixtures. Theoretical considerations as well as the identical spectra of the two peaks make plausible the appearance and separation of conformational isomers. PMID- 1887805 TI - [Analysis of steroids. Part 42. By-products of the ethynylation of 17 ketosteroids (isolation, identification and determination)]. AB - The therapeutically very important 17 alpha-ethynyl steroids are prepared from 17 keto steroids by means of addition of acetylene. Two important side reactions of this procedure are known: the formation of the isomeric beta-ethynyl derivative and the formation of a dimeric product with acetylene bridge. The aim of this paper is to approach this problem from the point of view of impurity profiling of 17 alpha-ethynyl steroids (norethisterone, ethisterone, norgestrel and delta 9(11)-ethisterone) i.e. isolation, identification and quantification of the above mentioned by-products as impurities in the bulk drugs. Capillary gas chromatography is an ideal tool for the separation and quantitative determination of the beta-ethynyl derivatives (20 m long fused silica capillary, I.D 0.2 mm; stationary phase Ultra-2: 5% phenylmethyl silicon gum phase with a film thickness of 0.33 mu; column temperature 240-250 degrees C). The dimeric impurity cannot be determined directly by gas chromatography as it decomposes in the flash heater to the 17 alpha-ethynyl and the 17-keto derivatives. For this reason reversed-phase HPLC was preferred for their separation and quantitation; (column: 250 x 4 mm LiChrosorb RP-18, 10 microns; eluent methanol-water 7:3; UV detector 240 nm). The HPLC method is suitable for the separation and determination of the beta-ethynyl impurities, too. The chemical shifts of the protons and carbon atoms in the vicinity of C-17 in the 1H and 13C NMR spectra of the epimeric 17-ethynyl steroids greatly depend on the configuration of the ethynyl group and for this reason they (especially that of the C-18 are eminently suitable for the characterization of the isomers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1887806 TI - [N-acetyl-beta-D-glucosaminidase as an early marker and indicator of the extent of kidney and liver lesions in endotoxemia and endotoxic shock]. AB - The aim of the study was to answer the question whether the serum level and the urine level of N-acetyl-beta-D-glucosaminidase (NAG) could be the indicator of liver and kidney lesions, and the indicator of the stage of the lesions, in cases of endotoxemia and endotoxin shock. The authors performed the experiment using 60 rabbits as experimental animals. The animals were divided into six groups (10 rabbits in each group); control animals received an equal volume (1.0 ml/kg of body weight) of physiological saline solution. Endotoxin (Lipopolysaccharide E. coli 055 B-5) in doses of 20, 40, 60, 80, and 100 micrograms/kg of body weight were administered in a single intravenous injection to each animal of I-V experimental groups. Using endotoxin in that dose of application, the authors provoked different stages of endotoxemia on the rabbits in the first four experimental groups, and the endotoxin shock on the rabbits of the fifth experimental group. After 18 hours, the rabbits were decapitated, and the levels of NAG in serum, urine, kidney and liver tissues determined. The results showed that the serum increase of NAG activity is caused not only by the lesions of kidney parenchyma, but by the lesions of liver parenchyma too, in the cases of endotoxemia and endotoxin-produced shock; the increase is statistically significant. Urine increase of NAG activity is significant even in cases in which the authors administered very low doses of endotoxin (20 micrograms/kg of body weight), so it can be said that urine NAG activity is a very good indicator of early kidney parenchyma lesions. But, the urine increase of NAG activity is (absolutely) in correlation with the dose of administered endotoxin, so it can be said that urine activity of NAG is the indicator of stage of kidney lesions in cases of endotoxemia and endotoxin-provoked shock. PMID- 1887807 TI - Brain shunts in patients with stroke: possible cerebral autoregulation of changed haemodynamics. AB - The cerebral perfusion was evaluated in 8 patients with stroke, caused by stenosis or occlusion of the carotid artery, and in 4 neurologically healthy subjects, using Tc99m labeled microspheres (LMS). By measuring activity in the brain and lungs after intracarotid injection of LMS, the existence of brain shunts in patients with stroke was demonstrated. It seems that brain ischaemia triggers the opening of shunts which appear to be one of the important autoregulatory and protective mechanisms to cerebral haemodynamic changes after brain infarction. PMID- 1887808 TI - Lenticulostriate arteries in aging process: an angiographic study. AB - Histological studies describe in detail the changes of the small arteries wall with controversial results concerning lumen narrowing during the aging process. In this study, the anatomic and the angiographic parameters of the medial and lateral lenticulostriate arteries were analysed in 64 carotid angiograms. Only 20% of the total number of lenticulostriate arteries were shown on angiograms. Collateral branches were rarely visible, especially those of medial group. The course of the lenticulostriate arteries was mostly straight or moderately tortuous. No significant differences were noted in any of the measured parameters when compared with the age (p greater than 0.05). It appears that age-related changes spread over external layers of small arteries, with no lumen narrowing or filling defect. PMID- 1887809 TI - Immunological reactivity in psoriatic arthritis. AB - Immunologic reactivity of patients with psoriatic arthritis and the influence of the activity of psoriatic arthritis on immunologic reactivity were analysed. The group of psoriatic arthritis patients, aged 17 to 65 years, consisted of 36 males and 13 females with confirmed diagnosis. 51 age and sex-matched volunteers served as the control group (32 males and 19 females aged 21 to 62 years). The following parameters of immunologic reactivity were analysed: number of leucocytes, percentage of the lymphocytes in peripheral blood, number and percentage of T lymphocytes with positive CD3, CD4 and CD8, number and percentage of B lymphocytes, number and percentage of B lymphocytes with surface IgG, IgA and IgM, number and percentage of large granular lymphocytes (LGL), lymphocytic transformation by phytohaemagglutinin and phagocytic index. The authors found statistically significant reduction of the number and percentage of CD4 T lymphocytes, number and percentage of B lymphocytes with surface IgG as well as significantly decreased lymphocyte transformation and phagocytic activity of peripheral granulocytes in patients with psoriatic arthritis in comparison to control group. PMID- 1887810 TI - Erythropoietin and improvement of anemia in long-term hemodialysis patients. AB - Two groups, with 4 patients each were selected for study out of 155 patients on regular hemodialysis (HD): Group I, with hematocrit (PCV) less than 20% and group II, with PCV greater than 30%. The patients in both groups had been anemic at the start of HD treatment, but a significant improvement in their anemia had occurred only among the patients in the Group II. The main difference between the two patient groups, other than the degree of anemia, was found to be in serum erythropoietin (Ep) levels. No significant differences were observed between the two groups in serum urea, creatinine, parathyroid hormone or CFU-E growth inhibition. Acquired cystic disease of the kidney was found in five patients from group I, and in 11 patients from group II. The correlation between the number of cysts in the kidneys and the patient's PCV and serum Ep levels proved significantly positive. The results presented could be regarded as another proof that diseased kidney is capable of functioning as an Ep producing organ despite the loss of excretory function. PMID- 1887811 TI - [Epidemiologic study of laryngeal cancer in Yugoslavia]. AB - In Yugoslavia cancer of the larynx has an important position in the group of malignant tumours, especially among the malignomas of the respiratory system. According to the data on mortality, laryngeal cancer accounts for 2.67% of all tumours and 11.59% of all respiratory tract tumours during the period from 1977 to 1988. In that period the average age-adjusted mortality rate of laryngeal cancer was 3.09 per 100,000 population, much higher in mean--6.29%(000) than the women--0.53%(000). The linear trend in laryngeal cancer mortality from 1977 to 1988 points to a slight increase (y = 2.97 +/- 0.02x), in men (y = 6.03 +/- 0.04x), while in women it shows a decrease (y = 0.60--0.01x). Age specific mortality rates of laryngeal cancer are low in the age groups to 39 years in men and 49 years in women. It augments steadily from 40 and 50 years of age respectively, with the highest rates in patients above 70 years of age (39.66%(000) for men and 4.05%(000) for women). PMID- 1887812 TI - C-reactive protein in sarcoidosis. AB - Sarcoidosis is characterized by granuloma formation, the macrophage being the most important building block. The activated macrophage in sarcoidosis produces interleukin-1 (II-1). It is well known that interleukin-1, among other functions, stimulates the hepatic production of C-reactive protein. We therefore prospectively measured the serum C-reactive protein in 17 patients with active pulmonary sarcoidosis, 10 patients with other chronic interstitial lung diseases of unknown etiology, 11 patients with active lung tuberculosis, and 10 healthy volunteers. Serum C-reactive protein was assayed by enzymoimmunodiffusion test. The serum C-reactive protein was negative in 13 patients suffering from active sarcoidosis and positive in four. Patients with other interstitial lung diseases had negative results in 7 and positive in 3 cases. The analyses of C-reactive protein in patients with sputum positive lung tuberculosis were positive in 10 cases. All the healthy controls had negative C-reactive protein measurements. The difference between the groups was statistically significant when sarcoidosis and tuberculosis serum C-reactive protein measurements were compared (p less than 0.01), as well as the difference between the group of other interstitial lung diseases and tuberculosis (p less than 0.01). In this respect, the measurements of serum C-reactive protein are valuable in the differentiation of sarcoidosis and other chronic interstitial lung diseases of unknown etiology from tuberculosis and other diseases which are known to induce an acute phase response. PMID- 1887813 TI - The importance of computer observation of postoperative complications in ophthalmology presented on the model of postoperative complications following cataract surgery. AB - Medical documentation is getting more extensive, it is not standardised and can hardly be used to provide the exact and proper feedback. The crisis of data storage, processing and uninterrupted flow of information is becoming concial in the medical institutions as well. An example of informatic model of observation of postoperative complications following cataract surgery is presented in this work. The model has a very flexible pattern, and can, therefore, with minor changes, be used in observation of all postoperative complications in ophthalmology. It is based on the use of personal computer with professional software support (data base III programme was used for creation of data base, while statistical graphic analysis was carried out by following programmes: MICROSTAT, ABSTAT, STATGRAPHIC and FRAMEWORK). It has to be pointed out that any doctor, after only a short (optional) education, could prepare such models for his own purposes, and could thus assist in overcoming the information in medicine. In conclusion, the authors state computer is simple to work with, fast, economical and precise. Computerisation of health service shall include it in one of the aspects of practical realisation of the third technological revolution. PMID- 1887814 TI - The spatial and temporal framework of the normal and the pathological in social psychiatry. AB - During the last four decades, parallel to the strategic and practical innovations that have occurred in social psychiatry, the concepts of the normal and the pathological have changed. As the normal and the pathological are determined and recognisable in both the spatial and the temporal framework, a change in these concepts can be assessed by tracing the shifts in their above mentioned fundamental dimensions. The spreading of the ideas and the practice of the community-centred psychiatry has brought about the greatest difficulties in defining the normal and the pathological. PMID- 1887815 TI - Mechanical loading, estrogen deficiency, and the coupling of bone formation to bone resorption. PMID- 1887816 TI - Estrogen binding and estrogenic responses in normal human osteoblast-like cells. AB - A finite human cell line was established from trabecular bone explants obtained from a 48-year-old woman. These cells, designated BG688, were characterized as osteoblast-like in phenotype using the following independent criteria: (1) the presence of histochemically detectable alkaline phosphatase (AP) activity; (2) response to the calciotropic hormone 1,25-(OH)2D3 as assessed by increased AP activity; (3) synthesis and secretion of the osteoblast-specific marker bone gla protein; and (4) expression of alpha 1(I)-procollagen and alpha 1(III) procollagen mRNAs in a pattern similar to that of other osteoblast-like cell lines. In addition to these classic osteoblast markers, BG688 cells also possess approximately 2400 high-affinity (Kd = 0.45 nM) 17 beta-estradiol (E2) binding sites per cell. The binding of E2 to these sites is specific, and of the steroid hormone agonists tested, E2 and diethylstilbestrol elicited the greatest amount of competition with radiolabeled E2. BG688 cells were also shown to respond to a physiologic concentration (10 nM) of E2. In vitro translation products of poly(A)+ RNA obtained from control and hormone-treated cells revealed a pleiotropic influence of E2 on the relative abundance of several mRNAs as assessed by two-dimensional gel electrophoretic analysis of their corresponding peptides. E2 also elicits a twofold increase in the steady-state concentration of alpha 1(I)-procollagen mRNA as demonstrated by northern blot hybridization. Thus, we here extend our previous data obtained in osteoblast-like osteosarcoma cells to indicate that a normal osteoblastic cell line is a target for the action of estrogen.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1887817 TI - In vitro studies on bone resorption in neonatal mouse calvariae using a modified dissection technique giving four samples of bone from each calvaria. AB - Bone resorption in a modified bone culture system, based on incubation of small fragments from neonatal mouse calvarial bones, has been studied. Four bone fragments were dissected out from each mouse calvaria and were thereafter cultured in CMRL 1066 medium in plastic multiwell dishes. Bone resorption was assessed by 45Ca release from prelabeled bones. The rate of bone resorption in response to parathyroid hormone (PTH) was less in the anterior part of the calvaria compared to the posterior part. After removing the anterior region, four parietal bone fragments that showed identical basal and PTH-stimulated release of 45Ca could be dissected out from each mouse. Excretion of lactate dehydrogenase and beta-glucuronidase was the same in bones cultured submerged or on grids. Uptake of [3H]thymidine in bones cultured submerged was 54% of [3H]thymidine uptake in bones cultured on grids. Dose-response curves, established by using parietal bone fragments, showed that the sensitivity and the magnitude of the increase in 45Ca release seen after stimulation with PTH, prostaglandin E2, and 1 alpha-hydroxyvitamin D3 were the same for bones cultured submerged or on grids. The 45Ca release in response to stimulation with PTH, prostaglandin E2, and 1 alpha-OHD3 was the same in calvarial fragments cultured submerged and those previously obtained with calvarial halves cultured on grids. Thus, even though the rate of DNA synthesis was slower in bones cultured submerged, the rate and the magnitude of resorption were the same in bones cultured on grids or submerged. These data show that it is possible to perform studies on bone resorption with small fragments of neonatal mouse parietal bones. PMID- 1887818 TI - Genetic determinants of bone mass in adult women: a reevaluation of the twin model and the potential importance of gene interaction on heritability estimates. AB - We estimated genetic effects on bone density in pre- and postmenopausal twins and critically considered the assumptions of the twin model. Bone mass in the radius, lumbar spine, and hip, anthropometric measurements, usual calcium and caffeine intake, tobacco and alcohol use, number of pregnancies and live births, menstrual history, usual physical activity, and medical history were measured in a volunteer sample of 171 twin pairs [124 monozygotic (MZ) and 47 dizygotic (DZ)], aged 25-80, free of diseases known to affect bone mass or mineral metabolism. At all skeletal sites, MZ intraclass correlations exceeded DZ correlations for both pre- and postmenopausal women, yielding highly significant estimates of heritability for bone mass. Adjustments for height, age, and environmental characteristics did not reduce the heritability estimates. However, many of these estimates were unrealistically high, suggesting some violation(s) of the assumptions of the twin model. Thus, the familial resemblance in bone mass is due primarily to genetic effects at all skeletal sites and at all ages, although the importance of genetic effects is diminished with aging, as evidenced by increasing within-MZ pair variability in older women. Because of failures in the assumptions of the twin model, however, particularly the greater MZ environmental similarity and the probability of gene interaction, heritability estimates are probably too high and require cautious interpretation. PMID- 1887819 TI - Superoxide dismutase and catalase activities in the growth cartilage: relationship between oxidoreductase activity and chondrocyte maturation. AB - Superoxide dismutase (SOD) and catalase are enzymes that protect cells from radical attack. Catalase disproportionates hydrogen peroxide, and SOD is an oxidoreductase that serves to dismutate the superoxide anion. The objective of this communication was to measure the activity of these disproportionating enzymes in the chick tibial growth cartilage and to relate enzyme activity to chondrocyte maturation and tissue calcification. Analytic techniques were optimized for the measurement of both enzymes; particular care was taken to ensure that the values obtained were due to SOD and catalase, not to the presence of other oxidases or contaminants. Catalase and SOD had similar profiles of activity in cartilage. For both enzymes, the highest levels of activity were observed in premineralized cartilage; as chondrocytes matured there was a progressive decrease in the activity of SOD and catalase. Comparison of chondrocyte SOD activity with nonmineralizing tissues indicated that the activity of cultured cartilage cells was low. We also measured the SOD activity of avascular chondrodystrophic cartilage and found it to be less than that of proliferating cartilage. When cartilage was electrofocused, three SOD isozymes were detected. The pI of the major isozyme corresponded to the copper-zinc isoform. We suggest that the observed changes in enzymatic activity are dependent on a number of cartilage-specific factors that include the vascular supply, the local production of oxygen radicals by chondrocytes, and the oxidative state of the tissue. PMID- 1887820 TI - Automated comparison of dual-photon absorptiometric studies of the lumbar spine. AB - An automated image comparison procedure was developed to optimize the precision of bone mineral density measurements by dual-photon absorptiometry. Changed acquisition conditions cause differences between two images to be compared. Alignment of one image with respect to the other is performed by a transformation that involves a rotation, a horizontal or vertical shift, and a correction for the soft tissue level. The best possible transformation is found in a stepwise search, guided by initial estimations of its parameters. After optimum transformation of one image, the region of interest of the other image is applied to both of them. Duplicate measurements of 9 patients and 15 normal subjects were performed; automated analysis yielded improved precision with respect to manual analysis. The coefficient of variation (CV) was also computed. The CV for automated analysis was 2.00% for patients and 1.04% for normal subjects compared to 3.55 and 1.93%, respectively, for manual analysis. For phantoms, the precision was 2.67% for manual analysis and 0.49% for automated analysis. PMID- 1887821 TI - Estrogen therapy and variable-resistance weight training increase bone mineral in surgically menopausal women. AB - This study was undertaken to examine the effect of estrogen replacement therapy alone and estrogen replacement therapy plus variable-resistance weight training on the bone mineral content of surgically menopausal women. A total of 20 surgically menopausal women were randomized and treated with either 0.625 mg conjugated estrogen daily or the same dose of estrogen plus a closely monitored exercise program involving the use of Nautilus muscle strengthening/endurance equipment. After 1 year's observation, the bone mineral density (BMD) of the spine determined by dual-photon absorptiometry increased in the exercising subjects by 8.3 +/- 5.3% (p = 0.004), 95% confidence limits (CL) 3.9-12.8%; the group with estrogen replacement therapy alone maintained their BMD: 1.5 +/- 12.4% (p = 0.36; 95% CL = -6.9-9.8%). The total body BMD of the exercising group increased by 2.1 +/- 1.5% (p = 0.003; 95% CL = 0.8-3.3%); the nonexercising women had a nonsignificant 0.6 +/- 2.9% change (p = 0.30; 95% CL = -1.4-2.5%). A significant increase of 4.1 +/- 4.3% (p = 0.01; 95% CL = 0.8-7.4%) in the radial midshaft BMD of the exercising group was found; the estrogen alone group recorded a nonsignificant change of -0.3 +/- 3.1% (p = 0.33; 95% CL = -1.7-2.4%). The results of this study suggest that variable-resistance training in estrogen replete women adds bone to both the axial and appendicular skeleton. PMID- 1887822 TI - Biphasic effect of calcitonin on tartrate-resistant acid phosphatase activity in isolated rat osteoclasts. AB - Tartrate-resistant acid phosphatase (TRAP) has been implicated as being involved in osteoclastic bone resorption, and calcitonin (CT) is known to inhibit the resorptive process. This study investigates the kinetics of CT action on TRAP activity in isolated rat osteoclasts using both biochemical and quantitative cytochemical methods. The latter technique has been developed to detect very small changes in intracellular TRAP activity at the single-cell level. The biochemical study showed that 10(-9) M salmon CT (sCT) decreased TRAP activity in medium throughout the experimental period; TRAP activity in the cells was increased during the first 2 h but subsequently declined and was decreased to a significant level at 6 h. TRAP activity in sCT-treated osteoclasts measured by the cytochemical method showed significant increases within the first hour. This response was dose dependent between 10(-16) and 10(-11) M sCT with EC50 at 8 X 10(-14) M. After 1 h, the initial increase in intracellular TRAP activity in CT treated osteoclasts was followed by a decline to below control levels, reaching statistical significance at 9 h. Treatment with forskolin (10(-5) M) showed a similar trend, suggesting that this response is mediated by cyclic AMP-regulated phosphorylation events. From these results, we conclude that CT has two actions on TRAP in isolated rat osteoclasts: the first to inhibit its release, the second to inhibit its synthesis and/or increase its degradation. PMID- 1887824 TI - Establishment and characterization of two immortalized cell lines of the osteoblastic lineage. AB - Osteoblastic cells were cloned by culturing rat calvariae cells in agarose in the presence of TGF-beta and EGF. Two bone cell lines were established by immortalizing such an osteoblastic clonal cell population by the introduction of the avian v-mycOK10 gene in the form of a mouse ecotropic retrovirus. Although originating from the same clonal cell population, the two lines exhibited somewhat differing properties. IRC10/30-myc1 expressed alkaline phosphatase (AP), showed PTH- and PGE2-induced cAMP production, synthesized mainly collagen type I and a minor fraction of type III, and produced mRNA for the bone-specific protein osteocalcin. IRC10/30-myc3 did not express AP, showed no PTH responsiveness, and synthesized only about one-third as much collagen as IRC10/30-myc1 (4 versus 12% of total protein synthesis). However, the cell line IRC10/30-myc3 was induced to synthesize cAMP by PGE2 and produced osteocalcin mRNA. When cultured in vivo in diffusion chambers, both lines proved to be osteogenic. Besides bone, both lines also formed cartilage and fibrous tissue. Thus, by immortalizing a clonal cell population of the osteoblastic phenotype, cell lines expressing varying properties can emerge. Furthermore, the expression of alkaline phosphatase and PTH-inducible adenylate cyclase are not prerequisites for a cell to form bone in vivo. Finally, cells expressing the phenotype of differentiated osteoblasts, including osteocalcin synthesis, still have a multipotential differentiation capacity and form bone and cartilage in vivo. PMID- 1887823 TI - Effects of guanine nucleotides and parathyroid hormone on inositol 1,4,5 trisphosphate metabolism in canine renal cortical tubular cell membranes. AB - Parathyroid hormone (PTH) and guanosine 5'-O-(3-thiotriphosphate) (GTP-gamma S) increase levels of the second messenger inositol 1,4,5-triphosphate (IP3) and other inositol phosphates (IP) in several membrane preparations of PTH-responsive cells. We present evidence here indicating that in a membrane preparation of canine renal cortical tubular cells bPTH-(1-84), bPTH-(1-34), [N Leu8,18Tyr34]bPTH-(3-34)NH2, and the human PTH related peptide fragment hPTHrP-(1 34)NH2 all increase levels of inositol phosphate (IP) but [Tyr34]-bPTH-(7-34)NH2 and hPTHrP-(7-34)NH2 have no significant effects on IP accumulation. Increases in IPs are generally attributed to increased formation of IPs and appear to be mediated by a G protein. However, increased levels of IPs may also result from inhibition of the phosphatases are responsible for their metabolism. We investigated the effect of PTH and GTP-gamma S on the metabolism of IP3 in canine renal cortical tubular membranes. These membranes rapidly metabolize [3H]IP3 (47% at 15 s). Decreases in [3H]IP3 at all time points are accounted for quantitatively by increases in the sum of its breakdown products: [3H]IP2, [3H]IP1, and [3H]inositol. After 5 minutes of exposure to membranes, the vast majority of [3H]IP3 (84%) is converted to its terminal metabolite, [3H]inositol. GTP-gamma S (100 microM) inhibits the amount of [3H]IP3 metabolized in 15 s by 70% and reduces the amount of [3H]inositol ultimately formed in 5 minutes by 64%. ATP-gamma S, ATP, and 2,3-bisphosphoglycerate (100 microM) also inhibit [3H]IP3 hydrolysis in this preparation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1887825 TI - Ascorbate uptake by ROS 17/2.8 osteoblast-like cells: substrate specificity and sensitivity to transport inhibitors. AB - Ascorbate (reduced vitamin C) is required for bone formation. We have shown previously that both the osteoblast-like cell line ROS 17/2.8 and primary cultures of rat calvarial cells possess a saturable, Na(+)-dependent uptake system for L-ascorbate (J Membr Biol 111:83-91, 1989). The purpose of the present study was to investigate the specificity of this transport system for organic anions and its sensitivity to transport inhibitors. Initial rates of ascorbate uptake were measured by incubating ROS 17/2.8 cells with [L-14C]ascorbate at 37 degrees C. Uptake of [L-14C]ascorbate (5 microM) was inhibited 98 +/- 1% by coincubation with unlabeled L-ascorbate (3 mM) and 48 +/- 4% by salicylate (3 mM), but it was not affected by 3 mM formate, lactate, pyruvate, gluconate, oxalate, malonate, or succinate. Uptake of the radiolabeled vitamin also was not affected by acute (1 minute) exposure of the cells to the Na+ transport inhibitors amiloride and ouabain or the glucose transport inhibitor cytochalasin B. In contrast, anion transport inhibitors rapidly (less than 1 minute) and reversibly blocked [L-14C]ascorbate uptake. In order of potency, these drugs were 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) approximately equal to sulfinpyrazone greater than furosemide approximately equal to 4-acetamido-4' isothiocyanostilbene-2,2'-disulfonic acid (SITS). These findings indicate that the ascorbate transporter is relatively specific for the ascorbate anion, since other organic anions (with the exception of salicylate) did not compete with ascorbate for uptake. Rapid and reversible inhibition by the impermeant antagonists DIDS and SITS suggests that they interact directly with the ascorbate transporter, consistent with location of the transport system in the plasma membrane. PMID- 1887826 TI - Urinary excretion of pyridinoline crosslinks correlates with bone turnover measured on iliac crest biopsy in patients with vertebral osteoporosis. AB - Vertebral osteoporosis, a common disorder in elderly women, is characterized by a wide spectrum of bone turnover abnormalities on iliac crest biopsy. The level of bone formation can be assessed noninvasively by measuring serum osteocalcin, whereas conventional biochemical markers of bone resorption lack specificity and do not reflect bone resorption assessed from histology. We measured the urinary excretion of pyridinoline crosslinks Pyr and D-Pyr, a specific marker of bone and cartilage collagen degradation, along with serum osteocalcin and urinary hydroxyproline, in 36 elderly women with vertebral osteoporosis who had a simultaneous iliac crest biopsy. Urinary pyridinoline crosslinks, but not hydroxyproline, correlated significantly with histologic resorption, assessed by the osteoclast surface (r = 0.35, p less than 0.05 for Pyr; r = 0.46, p less than 0.01 for D-Pyr). In addition, Pyr and D-Pyr were correlated with the bone formation rate as well as serum osteocalcin, with correlation coefficients ranging from 0.69 to 0.80, p less than 0.0001. These data indicate that Pyr and D Pyr are sensitive markers of bone turnover in elderly women with vertebral osteoporosis. The poor correlation between the level of urinary collagen crosslinks and histological assessment of bone resorption indicates the low sensitivity of iliac crest histomorphometry in the measurement of resorption rate of the skeleton. PMID- 1887828 TI - The high cost of higher education. AMA Investment Advisers, Inc. PMID- 1887827 TI - The notice of proposed rule making for the new Medicare physician payment system: AMA summary and analysis. PMID- 1887829 TI - Medical malpractice and access to obstetrical care in Alabama. AB - The medical malpractice insurance crisis of the mid-1980s has abated, but nonetheless there are concerns that the threat of liability continues to have a deleterious effect on access to obstetrical services for low income women. Currently, at the national level there is discussion over whether the tort system should be replaced with a no fault compensation scheme similar to the worker's compensation system. Florida and Virginia have already enacted no fault compensation schemes for certain birthrelated neurological injuries. After reviewing the situation in Alabama with respect to claim frequency and severity, insurance costs and access to obstetrical care, we will examine proposals for a fundamental restructuring of the medical liability system. PMID- 1887830 TI - Hospice--let it work for you. PMID- 1887831 TI - Current treatment of otitis media in children. AB - Otitis media is a common childhood disease with a spectrum of pathology ranging from acute, painful infection to persistent middle ear effusion to chronic negative middle ear pressure and development of cholesteatoma. Amoxicillin remains the initial empiric drug of choice with TMP-SMZ or erythromycin sulfisoxazole used for penicillinallergic patients or for amoxicillin therapy failures. Amoxicillin-clavulante, cefuroxime axetil (no elixir form available) or cefixime may then be tried keeping in mind relative costs, side effects, dosing frequency and drug formulation. Prophylactic amoxicillin or sulfisoxazole at one half the usual daily dose given once a day throughout the URI season is effective in reducing the number of episodes of AOME. Prolonged sulfonamide use should be carefully monitored. Tympanostomy tube insertion is indicated for frequently recurring otitis media and for persistent middle ear effusions. Adenoidectomy is an adjunctive procedure shown to be effective in children requiring a second set of tubes for recurrent infections or for children four years old or older with persistent middle ear fluid. Tympanoplasty may be necessary to prevent ossicular chain damage due to severe cases of MEVD or to repair non-healing perforations. Cholesteatomas must be surgically removed and may require elaborate reconstructive techniques. PMID- 1887832 TI - The Coke factor. PMID- 1887833 TI - 600,000 x 1. PMID- 1887834 TI - Commitment. PMID- 1887835 TI - Historical study: Johann Gregor Mendel 1822-1884. AB - The life and personality of Johann Gregor Mendel (1822-1884), the founder of scientific genetics, are reviewed against the contemporary background of his times. At the end are weighed the benefits for Mendel (as charged by Sir Ronald Fisher) to have documented his results on hand of falsified data. Mendel was born into a humble farm family in the "Kuhlandchen", then a predominantly German area of Northern Moravia. On the basis of great gifts Mendel was able to begin higher studies; however, he found himself in serious financial difficulties because of his father's accident and incapacitation. His hardships engendered illness which threatened continuation and completion of his studies until he was afforded the chance of absolving successfully theological studies as an Augustinian monk in the famous chapter of St. Thomas in Altbrunn (Stare Brno). Psychosomatic indisposition made Mendel unfit for practical pastoral duties. Thus, he was directed to teach but without appropriate state certification; an attempt to pass such an examination failed. At that point he was sent to the University of Vienna for a 2-year course of studies, with emphasis on physics and botany, to prepare him for the exam. His scientific and methodologic training enabled him to plan studies of the laws of inheritance, which had begun to interest him already during his theology training, and to choose the appropriate experimental plant. In 1865, after 12 years of systematic investigations on peas, he presented his results in the famous paper "Versuche uber Pflanzenhybriden." Three years after his return from Vienna he failed to attain his teaching certification a second time. Only by virtue of his exceptional qualifications did he continue to function as a Supplementary Professor of Physics and Natural History in the two lowest classes of a secondary school. In 1868 he was elected Abbot of his chapter, and freed from teaching duties, was able to pursue his many scientific interests with greater efficiency. This included meteorology, the measurement of ground water levels, further hybridization in plants (a.o. involving the hawk week Hieracium up to about 1873), vegetable and fruit tree horticulture, apiculture, and agriculture in general. This involved Mendel's active participation in many organizations interested in advancing these fields at a time when appropriate research institutes did not exist in Brunn. Some of the positions he took in his capacity of Abbot had severe repercussions and further taxed Mendel's already over-stressed system. The worst of these was a 10-year confrontation with the government about the taxation of the monastery.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1887836 TI - Joubert syndrome: a clinical and pathological description of an affected male and a female fetus from the same sibship. AB - A severely retarded male child with Joubert syndrome is described. He had severe neurological anomalies including Dandy-Walker malformation, hypoplasia of the corpus callosum, occipital meningo-encephalocele, and bilateral coloboma of the optic nerve with retrobulbar cystic mass. This is the first male described so far with both coloboma and other midline defects. A detailed autopsy on an affected female fetus from the mother's second pregnancy is presented. PMID- 1887837 TI - Father and two children with total anomalous pulmonary venous connection. AB - Total anomalous pulmonary venous connection (TAPVC) is a rare form of cyanotic congenital heart disease which, without surgical treatment, has a high mortality in the first year of life. Reports of familial recurrence of TAPVC have involved sibs, first cousins, and twins. This is the first report of TAPVC in a father and his 2 children. The implications for genetic counseling to families with this anomaly and individuals reaching adulthood after repair of TAPVC are considered. PMID- 1887838 TI - Metacarpophalangeal pattern profiles: Q-score for ages from birth to 7 years. AB - The metacarpophalangeal pattern profile (MCPP) analysis is a widely used method of standardization of bone length measurements to quantify congenital skeletal dysplasia of the hands. A main source of inaccuracy is the prominent scatter in the values of the standard deviation (S.D.) of the reference length, which is used in the calculation of the standardized values (Z-scores). Other sources of error, especially when bone length measurements of younger children are evaluated, are the rather large variability in the age of appearance of the epiphyses of the different bones, and the use of tabulated reference data which are available only at one-year intervals. We have devised another method of standardization of bone length measurements, by calculating the Q-score. Its advantages are that no S.D. values are needed and that more accurate results are obtained. Moreover the interpretation of the Q-scores is more straightforward than the interpretation of the Z-scores. Q-scores for 3 patients with Sotos syndrome are presented. Use of the MCPP in the form of the Q-score, will probably make it an even stronger tool than before. PMID- 1887839 TI - Creativity in medical genetics and dysmorphology. AB - One gauge of creativity in medical genetics and dysmorphology is the eponym. Conditions named for people reflect their powers of observation and analysis. We examined the fields and ages of 210 eponymous physicians and scientists whose biographies were published by Peter and Greta Beighton [1986] in The Man Behind the Syndrome. Twenty fields were represented with the dominant fields being, in order, pediatrics, neurology, general and internal medicine, pathology, radiology, and orthopedics. The ages of the eponymous workers averaged 43 years at the time of their relevant publications. Fully a fifth of the contributions were made by persons aged 30 years or less, or 60 years or more, suggesting that eponymous fame may come to workers of talent independent of age. PMID- 1887840 TI - Identification of the origin of centromeres in whole-arm translocations using fluorescent in situ hybridization with alpha-satellite DNA probes. AB - We detected 2 patients with whole-arm translocations resulting in a derivative chromosome consisting of 18q and 21q. Because the breakpoints were near the centromere, classical cytogenetic techniques could not determine the centromeric origin of the derivative chromosomes. Using nonradioactive in situ hybridization with a chromosome 18 alpha-satellite DNA probe (D18Z1), the centromeres in the abnormal chromosomes were determined to be from chromosome 18. The abnormality in one patient resulted in monosomy 18p with a karyotype 45,XX, -18, -21, + der(18)t(18;21) (p11;q11)mat complement. The second patient with a 46,XX, -21, + der(18)t(18;21)(p11;q11) de novo karyotype had complete trisomy of 18q. In both cases the appropriate phenotype was observed. PMID- 1887841 TI - Balanced X;3 translocation associated with gonadal dysgenesis: clinical report and review. PMID- 1887842 TI - Trichothiodystrophy and ichthyosis as diagnostic signs. PMID- 1887843 TI - Adams-Oliver syndrome associated with congenital heart defect: not a coincidence. PMID- 1887844 TI - Tracheoesophageal and anal atresia in prenatal children exposed to a high dose of alcohol. PMID- 1887845 TI - Forebrain cleavage gene causing holoprosencephaly: deletion mapping to chromosome band 2p21. PMID- 1887846 TI - Facio-cardio-renal (Eastman-Bixler) syndrome. AB - We report on a 5-year-old boy with moderate mental retardation, horseshoe kidneys, tricuspid valve prolapse, and a characteristic face with broad nasal root, prominent ears, and a cleft palate. These manifestations suggested the diagnosis of the Eastman-Bixler syndrome. Our patient also had an isolated growth hormone deficiency which responded successfully to treatment. PMID- 1887847 TI - Autosomal recessive Peters anomaly, typical facial appearance, failure to thrive, hydrocephalus, and other anomalies: further delineation of the Krause-Kivlin syndrome. AB - Two cousins and an unrelated patient, all offspring of consanguineous parents, presented with Peters anomaly, unusual facial appearance, disproportionate short stature, retarded skeletal maturation, and a variable degree of mental retardation. Variable digital, cardiac, CNS, and urogenital anomalies were present. The inheritance is probably autosomal recessive. The condition is a distinct clinical entity for which we suggest the eponym Krause-Kivlin syndrome. Peters anomaly is thought to result from abnormal migration of neural crest cells. A similar mechanism was implicated in the pathogenesis of other disorders of the anterior chamber. The presence of Peters anomaly, and possibly of other corneal endothelial disorders in a newborn infant, should alert the clinician to the possibility of this syndrome. Communicating hydrocephalus (or brain atrophy) and polyhydramnios were documented in two patients, potentially allowing prenatal diagnosis in secondary familial cases. PMID- 1887848 TI - Crossed polydactyly type I in a mother and son: an autosomal dominant trait? AB - In a Japanese family, a propositus and his mother had crossed polydactyly type I. A maternal grandaunt also had preaxial polydactyly of the feet. The findings that both of the mother and son had the identical type of polydactyly are consistent with an autosomal dominant inheritance with variable expressivity. Other explanations include X-linked recessive inheritance, polygenic inheritance, and a chance occurrence of the 2 different kinds of polydactyly. PMID- 1887849 TI - Chromosome instability and X-ray hypersensitivity in a microcephalic and growth retarded child. AB - We report on a microcephalic, growth-retarded newborn girl without major anomalies who has chromosome instability in lymphocytes and fibroblasts. Frequent involvement of bands 7p13, 7q34, 14q11, and 14q32 suggested the diagnosis of ataxia telangiectasia (AT) or a related disorder. Supportive evidence was radioresistant DNA synthesis in fibroblasts and radiation hypersensitivity of short-term lymphocyte cultures. Follow-up for nearly 4 years showed largely normal development, and no signs of telangiectasia, ataxia, or immunodeficiency. Serum AFP levels turned from elevated at age 5 months to normal at age 2 years. We propose that our patient belongs to the expanding category of "AT-related" genetic disorders, probably to the Nijmegen breakage syndrome. PMID- 1887850 TI - Penta X syndrome: a case report with review of the literature. AB - We describe a 6 month-old girl with a 49, XX-XXX chromosome constitution. The patient had a characteristic round face, a low hairline, hypertelorism, epicanthus, a long philtrum, high-arched palate, short and webbed neck, small hands and feet, clinodactyly of the fifth fingers, overlapping toes, and separation between the first and the second toes. She also had atrial septal defect and patent ductus arteriosus complicated by myocarditis which exacerbated the course of her congestive heart failure. Psychomotor development was retarded with opisthotonoid posture, axial hypotonia, and with a borderline abnormal EEG. A densitometric, transmission analysis on X-linked polymorphic DNA-fragments of the Southern blots of the patient and the parents, using P20/MspI and pERT87 1/XmnI as probe/enzyme combinations, showed that the pentasomy X had resulted from 3 successive nondisjunctions at maternal meiosis. Clinical manifestations among 22 previously reported penta X syndrome patients are also reviewed. PMID- 1887851 TI - Alagille syndrome associated with caudal dysplasia sequence. AB - A 36 day-old male with typical features of Alagille syndrome presented at birth additional features consistent with the diagnosis of caudal dysplasia sequence: imperforate anus, rectourethral fistula, lumbosacral abnormalities, and dysplastic right kidney. The association of these 2 conditions has not been previously reported, and could indicate the existence of an axial mesodermal dysplasia, of variable extension, in the Alagille syndrome. PMID- 1887852 TI - Waardenburg I syndrome: a clinical and genetic study of two large Brazilian kindreds, and literature review. AB - Two large kindreds with Waardenburg I syndrome are described. The total number of affected individuals is 73. The major manifestations are telecanthus (the only constant anomaly in all cases), prominent nasal root, round or square tip of nose, hypoplastic alae, smooth philtrum, bushy eyebrows with synophrys, sensorineural deafness, heterochromia or hypoisochromia iridis, hypopigmented ocular fundus, white forelock, premature greying, and hypopigmented skin lesions. These and other aspects of the syndrome, associated findings, frequency, genetic heterogeneity, pathogenesis, animal models, and gene linkage and mapping are reviewed briefly. PMID- 1887853 TI - Interstitial deletion of 4(q21q25) in a liveborn male. AB - We describe a liveborn male with a de novo deletion of 4(q21q25). The findings in this infant are compared with those of other 4q interstitial deletion patients with similar break-points. Given the reproducible findings including skull asymmetry, cardiac defects, renal cysts, "butterfly" vertebrae, as well as a particular dysmorphic face with developmental delay, there is evidence for an interstitial 4q deletion syndrome. PMID- 1887854 TI - Trisomy 14 mosaicism in a 5-year-old boy. AB - We report on a 5-year-old boy with failure to thrive, mental retardation, a broad nose, hypertelorism, slight antimongoloid slant palpebral fissures, mild ptosis, microphthalmia, short and wide neck, apparently acyanotic tetralogy of Fallot, dislocation of the left hip, generalized linear and patchy hyperpigmentation, micropenis, and undescended testes. He had mosaicism of 46,XY/47,XY, + 14 in a ratio of 3:1. Comparisons are made with the other reports of trisomy 14 mosaicism and relationship to incontinentia pigmenti. PMID- 1887855 TI - Newly recognized syndrome of cerebral, ocular, dental, auricular, skeletal anomalies: CODAS syndrome--a case report. AB - We report on a child with a unique constellation of congenital anomalies suggesting a new syndrome. These consist of developmental delay; craniofacial abnormalities, including bilateral cataracts, ptosis, median nasal groove, malformed ears with associated neurosensory hearing loss; dental anomalies consisting of anomalous cusp morphology with unusual pointed extensions and delayed tooth eruption; short stature with marked delay in epiphyseal ossification; coronal clefts involving vertebrae T11-S2; and dislocated hips. A literature search and use of a computer-assisted syndrome-identification program failed to uncover an identical case. PMID- 1887856 TI - Acrocallosal syndrome: a new case. AB - We describe a 2-month-old infant girl with typical clinical manifestations of the acrocallosal syndrome: characteristic face, agenesis of corpus callosum, polydactyly associated with other anomalies of the extremities, and mental retardation. The importance of a correct nosology and genetic counseling is underlined on the basis of the description of familiar cases of the syndrome. PMID- 1887857 TI - Congenital lung herniation. AB - Congenital lung herniation is a rare condition. It is usually associated with a costal cartilage defect. We report on a newborn boy with a partial lung herniation through the parietal pleura and skin associated with a sternal malformation. We propose the herniation occurred around the fifth month of fetal life and interfered with sternal ossification. PMID- 1887858 TI - Tissue factor antigen in senile plaques of Alzheimer's disease. AB - Tissue factor (tissue thromboplastin) is the primary initiator of the extrinsic coagulation pathway, triggering a proteolytic cascade when exposed to circulating coagulation factors. In this study, the distribution of tissue factor was examined immunohistochemically in Alzheimer's disease (AD) and control brains. Tissue factor was expressed diffusely in the neocortex, but in AD there was enhanced immunoreactivity in senile plaques. Although tissue factor might potentially contribute to the formation of senile plaques, it could also accumulate in the plaques as a secondary response to other biochemical perturbations. PMID- 1887859 TI - Transgenic oncogene mice. Tumor phenotype predicts genotype. AB - The hypothesis that oncogenes influence tumor phenotype was tested by examining slides from 607 mammary tumors from 407 transgenic mice bearing the ras, myc, and/or neu oncogenes. Most tumors (91%) had patterns (phenotypes) that could not be classified by Dunn's standard nomenclature. The nonstandard tumors were described as eosinophilic small cell (SC), basophilic large cell (LC), or pale intermediate cell (IC). The SC tumor was associated with ras, the LC was associated with myc, and the IC was associated with neu, with specificities more than .90 and sensitivities ranging from .99 to .48. Thus, the tumor phenotype could be used to predict which oncogene was present in the animal. The presence of myc in combination with either ras or neu resulted in the predominance of LC tumors and accelerated tumorigenesis. The combination of ras and neu resulted in a decreased tumor incidence. Thus, knowledge of the oncogenes that were present could be used to predict the natural history of the disease. PMID- 1887860 TI - Activated T-cell subsets in benign lymphoid hyperplasias and B-cell non-Hodgkin's lymphomas. AB - Activated tumor-infiltrating T lymphocytes (TIL-T) were quantitated prospectively in excisional biopsy specimens of 49 B-cell non-Hodgkin's lymphomas (NHL) of various grades and compared with eight benign lymphoid hyperplasias (BLH) to identify any potential difference in host T-cell response. Immunotyping of tissue cell suspensions was done by three-color flow cytometry, which was complemented by immunocytology by using cytocentrifuged preparations. Two activated T-cell subsets were studied: acutely activated TIL-T (CD3+ CD25+ HLADr-) and chronically activated TIL-T (CD3+ CD25- HLADr+). Results showed an association of the more aggressive intermediate/high-grade B-cell NHL with a higher percentage of late phase activated TIL-T and a progressive increase with the grade of malignancy: 10.29%, 23.25%, 33.87%, and 47.78% (means) for BLH and for low-, intermediate- and high-grade B-cell NHL, respectively. Differences for this subset were significant (P less than 0.050) for the following comparisons: hyperplasia versus intermediate-grade NHL (P less than 0.0012), hyperplasia versus high-grade NHL (P less than 0.0002), and low versus high-grade NHL (P less than 0.0080). The percentage of acutely activated TIL-T cells did not show a statistically significant difference between the groups. The results suggest a host T-cell response to proliferating neoplastic cells in B-cell NHL. Paradoxically, the response does not appear to be protective for the host since the intensity is directly proportional to the grade of malignancy. However, the recognition of this response may have clinical applications since its amplification with biological response modifiers may result in effective adoptive immunotherapy of B cell NHL. Further clarification of the specificity and biologic significance of host T-cell activation in B-cell NHL will require functional studies of isolated lymphocytic subpopulations from neoplastic tissue. PMID- 1887861 TI - Pathogenic significance of serum components in the development of autoimmune polyarthritis in MRL/Mp mice bearing the lymphoproliferation gene. AB - MRL/Mp mice bearing the lymphoproliferation gene (lpr) (MRL/Mp-lpr/lpr) spontaneously develop polyarthritis, associated with autoimmune traits, including rheumatoid factor production, which resembles rheumatoid arthritis. To investigate possible arthritogenic activity of serum of these mice, intraarticular injections of the serum components to knee joints of nonarthritic MRL/Mp mice not bearing the lpr gene (MRL/Mp(-)+/+) were performed. Two fractions from the serum were obtained by a gel chromatography. The void fraction (VF), but not the nonvoid fraction (NVF), induced acute inflammatory lesions in the joints by single injection, and destructive arthritis by repeated injections. VF had immune complex activity, and contained a large amount of cryoglobulin, which in itself was found arthritogenic. These findings indicate that the serum components of MRL/Mp-lpr/lpr mice have a potency to cause destructive arthritis. These results are direct evidence in a syngeneic animal model system, which suggests the pathogenic significance of serum components in rheumatoid arthritis. PMID- 1887862 TI - Morphologic features and nuclide composition of infarction-associated cardiac myocyte mineralization in humans. AB - Low dietary Mg results in Ca loading of cardiac myocytes, which increases the likelihood of myocyte calcification in the event of acute myocardial infarction (AMI), and possibly increases myocyte vulnerability to necrosis. Bloom and Peric Golia1 previously reported an autopsy study of cases from the Washington, D.C. area (a region with low levels of Mg in the drinking water), demonstrating AMI associated mineralization in myocytes with histologically normal nuclei and cross striations, as well as in obviously necrotic myocytes. The authors have re examined mineralized myocytes from the same autopsy material, using electron probe microanalysis, light microscopy, and transmission electron microscopy. Microprobe analysis identified Ca and P as the nuclides composing the inorganic phase of the mineral deposits. Ultrastructurally, all Ca deposits, regardless of size or intracellular location, were composed of aggregates of needlelike hydroxyapatite crystals. The mildest form of intracellular Ca deposition was observed as small Ca deposits limited to some mitochondria of myocytes, which demonstrated intact nuclei and regular sarcomere pattern. More advanced stages of intracellular calcification, in the form of Ca deposits associated with mitochondria, Z-band regions and nuclei, were observed in other myocytes that also retained intact nuclei and sarcomeres. Massive Ca deposits were associated with myocytes which showed morphologic features of advanced necrosis, including loss of nuclei, disruption of sarcomere structure and masses of cellular debris. These observations support the theory originally proposed by Bloom and Peric Golia1 suggesting that Ca loading of myocytes, possibly related to Mg deficiency in humans, increased vulnerability of the myocytes to subsequent AMI-associated necrosis and dystrophic calcification. In addition, the light microscopic impression of calcification of otherwise normal myocytes is contradicted by the electron microscopic identification of hydroxyapatite crystals free in the sarcoplasm, a condition unlikely to be compatible with viability. Lastly, the fact that all Ca deposits were in the form of hydroxyapatite supports the view that they were formed in a Mg-poor environment, which favors conversion of the more common amorphous form of Ca phosphate into the needlelike crystals of hydroxyapatite. PMID- 1887863 TI - Inhibition of vein graft intimal proliferative lesions in the rat by heparin. AB - The authors investigated the effect of heparin on the development of myointimal proliferative lesions in a rat vein graft model. Intimal thickening in this model was most pronounced in the anastomotic regions, and was composed principally of vascular smooth muscle cells, as identified by immunocytochemistry with anti muscle actin antibody, HHF-35. Medial thickening was less cellular, and evenly distributed throughout the grafts. Continuous, intravenous infusion of whole heparin at 0.3 mg/kg/hr effectively inhibited the development of myointimal proliferative lesions, although with no effect on medial thickening. The authors suggest that heparin, through its antiproliferative activity for vascular smooth muscle cells, may have a potentially important pharmacologic role in preventing vein graft failure, which most commonly results from the development of myointimal proliferative lesions. PMID- 1887864 TI - Alpha 1-antitrypsin is present within the primary granules of human polymorphonuclear leukocytes. AB - Elastase is a potent proteolytic enzyme found within human neutrophil primary granules. Its major inhibitor in the serum is alpha 1-antitrypsin, a protein that is synthesized by hepatocytes but which has recently also been shown to be synthesized by circulating neutrophils. The authors have therefore carried out an immunocytochemical study at the light microscopic and ultrastructural level to determine the intracellular localization of alpha 1-antitrypsin. Double labeling with colloidal gold showed that alpha 1-antitrypsin is localized at the same site as neutrophil elastase, i.e., within primary granules. Secondary granules (detected by labeling for lactoferrin) were unstained for alpha 1-antitrypsin. Elastase and its major inhibitor therefore coexist within the same granule population within human neutrophils. Some difference in their intraorganelle distribution existed at the ultrastructural level (in that elastase tended to be localized at the periphery of the granules whereas alpha 1-antitrypsin was usually diffusely present in the matrix of the granules), but further studies are required to determine whether the two molecules are already complexed with each other within the neutrophil. PMID- 1887865 TI - Abnormal differentiation of tissue macrophage populations in 'osteopetrosis' (op) mice defective in the production of macrophage colony-stimulating factor. AB - Examination of the op/op mouse disclosed marked reduction and abnormal differentiation of osteoclasts in the bones and of tissue-specific macrophages in various visceral organs and tissues. Most of these macrophages were immature as judged by ultrastructural criteria. In co-cultures of normal mouse bone marrow cells with fibroblast cell lines prepared from the lungs of the op/op mice, a defective differentiation of monocytes into macrophages was confirmed, supporting previous evidence that the fibroblast cell lines of the mutant mouse failed to produce functional macrophage colony-stimulating factor (M-CSF/CSF-1). In such co cultures, however, a small number of macrophages apparently mature under the influence of granulocyte/macrophage colony-stimulating factor (GM-CSF) produced by the op/op fibroblast cell lines. In the mutant mice, the numbers of macrophages in the uterine wall and ovaries were severely reduced. Compared with the tissues of normal littermates, those of the mutants contained about 60% fewer macrophages in many tissues. This suggests that an M-CSF-independent population of macrophages is derived from granulocyte/macrophage-colony-forming cells (GM CFC) or earlier hematopoietic progenitors. PMID- 1887866 TI - Comparative morphologic and immunohistochemical studies of estrogen plus alpha naphthoflavone-induced liver tumors in Syrian hamsters and rats. AB - Syrian hamsters were treated with ethinylestradiol and maintained on a diet containing alpha-naphthoflavone (alpha NF), a regimen that produces a high incidence of liver tumors. Morphologic analyses (light microscopy, immunoperoxidase studies, and electron microscopy) were performed on livers of these animals. After 4 months of hormone plus alpha NF treatment, marked hepatocyte cell changes were already present, as demonstrated by loss of eosinophilic staining of hepatocyte cytoplasm. Large multinucleated hepatocytes exhibiting frequent mitoses were observed around central veins. After 5 months of treatment, there was proliferation of bile ducts, and small cells with eosinophilic cytoplasm resembling hepatocytes appeared surrounding these bile ducts. At 7 to 8 months, the first tumor nodules (foci) were seen. Tumor foci in the portal area consisted of small clusters of large cells resembling hepatocytes with irregular nuclei. At the same time, dysplastic glands were identified among proliferating bile ducts. By 8 to 10 months, large tumors were present. These were trabecular hepatocellular carcinomas with widely varying individual cell morphology. Compared with adjacent liver, dysplastic glands in the portal areas, microcarcinomas, and large tumors all showed intense immunostaining for cytokeratin. Rats treated with the same regimen also developed hepatic tumors, but the light and electron microscopy results and immunohistochemical profiles were very different. Altered hepatic foci composed of small hepatocytes were typically prominent; however, malignant tumors did not arise from the portal area. Neither altered foci nor tumors stained significantly for cytokeratin. These data suggest that the biochemical events giving rise to these liver tumors differ between the species studied, despite the animals being exposed to the same treatment regimens. PMID- 1887867 TI - Hereditary polycystic kidney disease. Adult polycystic kidney disease associated with renal hypertension, renal osteodystrophy, and uremic enteritis in SPRD rats. PMID- 1887868 TI - Histamine H1-receptor-mediated keratan sulfate production in rabbit chondrocytes: involvement of protein kinase C. AB - We investigated the characteristics of the histamine H1-receptor in cultured rabbit chondrocytes. Scatchard analysis of [3H]pyrilamine, an H1-antagonist, binding to the chondrocytes revealed a single class of binding sites with KD and Bmax values of 90 +/- 12 nM and 56 +/- 11 fmol/10(4) cells, respectively. H1 agonists stimulated the production of keratan sulfate in a dose-dependent manner. Stimulation of keratan sulfate production was inhibited by pyrilamine. Protein kinase C inhibitors (sphingosine and H-7) also had inhibitory effects. Phorbol 12,13-dibutyrate, a direct activator of protein kinase C, activated the production. When protein kinase C in the chondrocytes was down-regulated by preincubation with phorbol ester, the effect of the H1-agonist on keratan sulfate production was abolished. These results indicate that the histamine H1-receptor on chondrocytes mediates the accumulation of keratan sulfate production and that protein kinase C is involved in these events. PMID- 1887869 TI - Changes in pattern of phospholipid acylation during in vivo aging of rat red blood cells. AB - We have investigated the patterns of incorporation of stearic, oleic, and linoleic acids into phosphatidylcholine (PC) and phosphatidylethanolamine (PE) of intact red blood cells of differing age isolated by centrifugation on discontinuous density gradient. Acylation rates of PC and PE elicited marked declines from the reticulocyte to the young erythrocyte stage followed by minimal changes of acylating potency in older cells; this biphasic decay pattern was similar with the three fatty acids. Molar acylation rates were higher for PC than for PE in reticulocytes, whereas they were comparable in erythrocytes. PC served as preferred fatty acid acceptor in circulating red blood cells, a function which was largely accounted for by PC contained in the small percentage of circulating reticulocytes. On a per cell basis, this function of PC was due to the cumulative effects of higher molar acylation rates in reticulocytes and higher content in PC over PE in the red blood cell membrane. Acylation rates in PC and PE increased with the number of unsaturated bonds in the acylating fatty acid, regardless of cell age. PMID- 1887870 TI - Estrogen modulates phospholipid acylation in red blood cells: relationship to cell aging. AB - Ethinyl estradiol administered in vivo to female rats resulted in a mild anemia with a 120% increase in reticulocytosis. Consistent with a previous study, the red blood cell cholesterol-to-phospholipid molar ratio was decreased by 25%, whereas fatty acyl incorporation was significantly increased into phosphatidylethanolamine (PE) and not into phosphatidylcholine (PC), the major acyl acceptor in red blood cells. Analysis of this estrogen-dependent acylation increase as a function of cell age indicated that it was not expressed in reticulocytes but in erythrocytes and was associated with cell aging. Estrogen was further shown to increase the red blood cell susceptibility to peroxidation generated by incubation with H2O2. Altogether, the results suggest that estrogen indirectly increases phospholipid acylation in red blood cells by decreasing protection against oxidative damage, thereby favoring the action of endogenous phospholipases against oxidized substrates. This occurs predominantly in PE of oldest cells because 1) PE, being more unsaturated than PC, is more sensitive to oxidation, and 2) susceptibility to oxidation increases with cell age. PMID- 1887871 TI - Effect of flow on prostaglandin E2 and inositol trisphosphate levels in osteoblasts. AB - Osteoblasts in culture respond to mechanical strains. Fluid flow has been shown to increase intracellular adenosine 3',5'-cyclic monophosphate levels in cultured osteoblasts, and this response is mediated by prostaglandin synthesis. The signal transduction pathway of these cells exposed to fluid flow is still unknown. In the present study, we have demonstrated a 9- and 20-fold increase in the rate of prostaglandin E2 (PGE2) production in osteoblasts exposed to low (6 dyn/cm2) and high (24 dyn/cm2) steady shear, respectively. We further observed that fluid flow induced increases in the intracellular levels of inositol trisphosphate (IP3), another important second messenger. A shear stress of 24 dyn/cm2 increased IP3 levels dramatically for up to 2 h. Removal of flow resulted in a gradual return of IP3 to basal levels. The stimulation of IP3 levels was partially inhibited by 20 microM ibuprofen and 14 microM indomethacin, indicating that the IP3 response was partly dependent on flow-induced prostaglandin synthesis. The IP3 response was unaffected by daltroban, a specific thromboxane antagonist. These results show that fluid flow induced prostaglandin E2 production and increased intracellular levels of IP3 in osteoblasts. This suggests that flow may be the external signal produced by loading and that these messengers may be involved in the transduction of mechanical strain into a biochemical response. PMID- 1887872 TI - Disappearance of the protein of a somatic mutation: a possible example of stem cell inactivation. AB - The low concentration of the hemoglobin variant, Hb Vicksburg (leucine-beta-75 deleted), and a profound deficit of its mRNA led us to postulate that a beta(+) thalassemia mutation existed in cis to the coding region mutation, suppressing its synthesis. We examined blood from this patient 6, 8, and 10 yr after our initial studies, using methods of analysis unavailable initially. We found 1) mutations causing beta(+)-(-88 C----T) and beta 0-(849 A----G) thalassemia; 2) that the proportion of Hb Vicksburg in erythrocytes fell over time, from 8 to 4%, and ultimately disappeared; and 3) that the mutation causing Hb Vicksburg was not detectable in genomic DNA isolated from blood leukocytes when this variant was present in hemolysate. We postulate that Hb Vicksburg arose from a somatic mutation of a beta(+)-thalassemia gene in an erythroid-committed stem cell. Its gradual disappearance suggests the cycling of stem cells, with inactivation of different clones over time. PMID- 1887873 TI - Developmental regulation of the hepatic acute phase response. AB - For evaluation of the ontogenetic regulation of the acute phase response, inflammation was induced in Fischer rat litters at different postnatal ages. Four homologous rat hepatic serine protease inhibitor (Spi 2.1, Spi 2.2, Spi 2.3, and alpha 1-antitrypsin) mRNAs were measured in livers 24 h after injection. Animals mounted both positive and negative acute phase responses at all ages, but responses were blunted in young animals, reaching adult levels by days 7-19. alpha 1-Antitrypsin mRNA had no response, and Spi 2.2 mRNA had 50% the rise seen in adults on days 3 and 7. Spi 2.1 and 2.3 mRNAs, negative acute phase reactants, showed attenuation of adult response to inflammation in infant animals of 33% (Spi 2.1) and 40% (Spi 2.3). In hypophysectomized animals, the responses of Spi 2.2, 2.3, and alpha 1-antitrypsin mRNAs after turpentine stimulation were similar to that of normal animals, whereas Spi 2.1 mRNA did not change. In conclusion, infant animals mount a blunted response to tissue injury; multiple factors may be involved in the development of the full adult response. Immaturity of the pituitary may play a role in the suppression of Spi 2.1 mRNA's response during inflammation in infant animals. These highly evolutionary related genes will be helpful in identifying specific factors regulating gene expression in inflammation and development. PMID- 1887874 TI - Mn and Cd transport by the Na-Ca exchanger of ferret red blood cells. AB - Ca influx via the Na-Ca exchanger into ferret red blood cells is easily measured from a Na-free solution; the intracellular Na concentration is normally approximately 150 mM in ferret red blood cells. We have found that Mn and Cd competitively inhibit Ca influx. Mn influx and Cd influx were a saturable function of the divalent cation concentration, consistent with a carrier mechanism. Indeed, the Km (approximately 10 microM) and the Vmax (usually 1-3 mmol.l packed cells-1.h-1) were similar for Ca, Cd, and Mn. Extracellular Na inhibited divalent cation influx, and intracellular Na stimulated influx. These results are consistent with Na-Cd and Na-Mn influx pathways in ferret red blood cells. Ca (1 mM) almost completely inhibited Mn influx and Cd influx, whereas 1 mM Mg inhibited 5-15%. These results strongly support the notion that Mn and Cd are alternative substrates for Ca on the ferret red cell Na-Ca exchanger. The similarity in the behavior of all three divalent cation places important constraints on kinetic and structural models of the exchanger. PMID- 1887875 TI - Carbachol-stimulated phosphorylation of a 170-kDa endogenous protein in avian salt gland cells. AB - The effect of cholinergic stimulation of cellular protein phosphorylation was studied using an intact cell preparation isolated from the avian salt gland. Isolated cells were allowed to incorporate 32Pi into the cellular ATP pool and then challenged with compounds known to induce ion secretion in this tissue. Addition of carbachol resulted in a time- and concentration-dependent (EC50 = 500 nM) increase in 32Pi content of a 170-kDa protein (pp170). The stimulated phosphorylation could be blocked by the inclusion of atropine (100 microM). Subcellular fractionation studies localized pp170 to the plasma membrane fraction of the tissue. The integral nature of this protein was demonstrated by detergent solubilization experiments with Triton X-100. The possibility that carbachol stimulates phosphorylation of pp170 via activation of protein kinase C (PKC) was investigated. Incubating salt gland cells with 4 beta-phorbol 12-myristate 13 acetate (PMA; 1 microM) or carbachol (100 microM) resulted in a translocation of soluble PKC from the cytosol to a plasma membrane fraction. Addition of either PMA (1 microM) or ionomycin (1 microM) alone did not enhance phosphorylation of pp170. A 4.5-fold increase in the phosphorylation state of pp170 was only observed when PMA and ionomycin were added concurrently. Preincubation of salt gland cells with PKC inhibitors H-7 (50 microM) or staurosporine (10 microM) inhibited the carbachol-stimulated phosphorylation of pp170. These findings suggest that carbachol mediates its secretomimetic effects via activation of PKC and that pp170 may represent a novel integral membrane PKC substrate protein. PMID- 1887876 TI - Ventromedial hypothalamic stimulation enhances peripheral glucose uptake in anesthetized rats. AB - Effects of electrical and chemical stimulation of the ventromedial (VMH) and lateral hypothalamic (LH) nuclei on glucose uptake in peripheral tissues were studied by the 2-deoxy-D-[3H]glucose (2-[3H]DG) method in anesthetized rats. Electrical stimulation of the VMH increased the rate constant of glucose uptake in brown adipose tissue (BAT; 8 times), heart (3 times), and skeletal muscles (1.5 times) but not in white adipose tissue, diaphragm, and brain, without detectable changes in plasma insulin levels. Chemical stimulation of the VMH by microinjection of L-glutamate also enhanced the rate constant of glucose uptake in BAT, heart, and skeletal muscles preferentially, which indicates that the enhancement of glucose uptake in these tissues is derived from activation of VMH neurons. The increased rate of glucose uptake in BAT in response to VMH stimulation was effectively suppressed by surgical sympathetic denervation, suggesting a mediation of the sympathetic nerve in this effect. On the other hand, electrical stimulation of the LH had no appreciable effect on 2-[3H]DG uptake in any tissues. It is concluded that glucose uptake in certain peripheral tissues is accelerated selectively by activation of VMH neurons, the action of which is independent of plasma insulin but which is probably via the sympathetic nervous system. PMID- 1887877 TI - Bidirectional saturable transport of LHRH across the blood-brain barrier. AB - Systemic administration of luteinizing hormone-releasing hormone (LHRH) in rats has been found to influence behavior independently of pituitary or ovarian function. A previous study has shown that LHRH can cross the blood-brain barrier in one direction, but it was not known whether this was due to a saturable transport system. The rate of entry of 125I-labeled LHRH from blood to brain was determined by two different single-pass methods of carotid perfusion. The first, a multiple time point method, measures Ki from the slope of the linear regression when brain-to-blood ratios of radioiodinated LHRH are plotted against time. Saturable transport was determined by the difference between the Ki of rats perfused with 125I-LHRH (12.51 X 10(-3) mg.g-1.min-1) vs. rats perfused with 125I LHRH and unlabeled LHRH (10 nmol/ml; 2.20 X 10(-3) ml.g-1.min-1). The inhibition by the unlabeled peptide was statistically significant (P less than 0.001). The second method, a single time point technique, measures the cerebrovascular permeability-surface area coefficient (PA). Saturable transport was determined in rats by the competition of unlabeled LHRH with 125I-LHRH. The PA value for 125I LHRH (20.00 X 10(-3) ml.g-1.min-1) was significantly greater (P less than 0.05) than for 125I-LHRH with the addition of 10 nmol/ml unlabeled LHRH (4.14 X 10(-3) ml.g-1.min-1). Saturable transport of LHRH from brain to blood in mice was also determined.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1887878 TI - Structural requirements of pancreatic polypeptide receptor binding. AB - Pancreatic polypeptide (PP) receptors have been identified and characterized on the basolateral membranes (BLM) of canine intestinal mucosa. The present study was designed to ascertain the structural requirements of the PP molecule for binding to its receptor. A radioreceptor assay using purified BLM was employed to elucidate receptors specific to PPs of various mammalian species and to modified bovine PP (bPP) fragments. Receptor cross-reactivities (CR) to various PPs and bPP fragments were established. Results show that percent receptor CR by PPs of various species was as follows: bPP (100%) greater than human PP (68%) greater than porcine PP (50%) greater than canine PP (45%) greater than ovine PP (36%) greater than rat PP (3%). The fragments bPP-(1-15), bPP-(1-17), bPP-(1-26), bPP (16-23), bPP-(18-30), bPP-(24-36), bPP-(27-35), and bPP-(31-36) at 500 nM did not significantly displace tracer from receptor (less than 0.1% CR). Des-COOH terminal tyrosinamide [bPP-(1-35)] produced less than 0.1% CR. Oxidation of bPP methionine-30 residue to methionine sulfoxide decreased displacement to 67%. Modification of native amidated tyrosinamide to the free acid abolished receptor binding, whereas esterification to the methyl ester of COOH-terminal tyrosine restored binding to 60%. Additionally, percent CR decreased progressively as amino acid residues were deleted from the NH2-terminal region. We conclude that the molecular homologue of PP primary structure is necessary for full receptor binding. Both the NH2- and COOH-terminal residues are required for recognition, and the COOH-terminal tyrosinamide must be intact for PP binding to its receptor. PMID- 1887879 TI - Effects of calmodulin antagonists on hydrogen-translocating shuttles in perfused rat liver. AB - The effects of calmodulin antagonists on the capacity of hydrogen-translocating shuttles were studied in the perfused rat liver. The capacity was estimated by measuring the changes in the rate of production of glucose from sorbitol during the oxidation of ethanol [T. Sugano, T. Ohta, A. Tarui, and Y. Miyamae. Am. J. Physiol. 251 (Endocrinol. Metab. 14): E385-E392, 1986]. Thyroxine given to intact rats increased the activity of alpha-glycerophosphate dehydrogenase (alpha-GPD). Glucocorticoid replacement in adrenalectomized rats decreased the activity of the alpha-GPD to values obtained after treatment with PTU. In either thyroxine treated or steroid-replaced rats, the capacity of hydrogen-translocating shuttles increased markedly. However, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), trifluoperazine, and chlorpromazine inhibited the increased capacity in steroid-replaced rats and had no effect on the increased capacity in thyroxine treated rats. W-7 inhibited the stimulatory effects of norepinephrine on the capacity of the malate-aspartate shuttle without inhibition of efflux of intracellular Ca2+. The stimulatory effects of vasopressin on the malate aspartate shuttle were also inhibited by W-7, trifluoperazine, and chlorpromazine. The results suggest that the malate-aspartate shuttle may be regulated by Ca(2+)-calmodulin. PMID- 1887880 TI - Application of mass isotopomer analysis for determination of pathways of glycogen synthesis. AB - An elementary exposition of the application of mass spectroscopy to studies with substrates labeled uniformly with 13C is presented. A procedure to obtain mass isotopomer spectra, corrected for natural abundance, of products labeled with 13C in several positions is outlined. The calculation for enrichment, a term equivalent to specific activity with radioisotopes, is shown. Examples of mass isotopomer patterns of blood glucose and glycogen are presented, and calculations of the contribution of the direct path to hepatic glycogen synthesis and the dilution of glucose-derived pyruvate are shown. The analysis of mass isotopomer patterns recently offered by C. Des Rosiers, B. R. Landau, and H. Brunengraber [Am. J. Physiol. 259 (Endocrinol. Metab. 22): E757-E762, 1990] is critically examined. PMID- 1887881 TI - In vivo location of the rate-limiting step of hexose uptake in muscle and brain tissue of rats. AB - The uptake of glucose proceeds via facilitated transport from the plasma followed by phosphorylation of intracellular glucose. We have quantified the relative contribution of transport and phosphorylation to the overall rate of hexose utilization into the quadriceps muscle (red and white) and cerebellum of rats anesthetized with pentobarbital sodium. The method employed simultaneous infusions of radiolabeled 3-O-methyl-D-glucose and 2-deoxy-D-glucose. Results were expressed in terms of a parameter ft*, which has theoretical limits of 0 and 1 corresponding to phosphorylation and transport limitation, respectively. In cerebellum, basal rates of transport and phosphorylation were comparable (ft* = 0.32 +/- 0.02). Under conditions of hyperglycemia plus maximum insulin stimulation, phosphorylation limited glucose utilization to a greater extent (ft* = 0.12 +/- 0.02). No effect of hyperinsulinemia alone was observed. In red muscle, transport determined overall glucose utilization in the basal (ft* = 0.96 +/- 0.05) and euglycemic insulin-stimulated states (ft* = 0.90 +/- 0.02). A shift of the rate-limiting step from transport toward phosphorylation was observed in insulin-stimulated red muscle when blood glucose (ft* = 0.64 +/- 0.05) or epinephrine levels (ft* = 0.66 +/- 0.07) were elevated. Neither effect was seen in white muscle. We conclude that the transport step dominates but is not the only determinant of muscle hexose utilization under all conditions. PMID- 1887882 TI - Correlation between mRNA levels for bone cell proteins and bone formation in long bones of maturing rats. AB - This report describes the relationship between bone formation and mRNA levels for selected bone proteins. Dynamic bone histomorphometry was used to measure bone formation in tibial periosteum of male rats from weanling (3 wk) to 52 wk old. Northern blot analysis of freshly isolated periosteal cells from the long bones was used to determine steady-state mRNA levels for the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAP), the bone matrix proteins osteocalcin (BGP), and prepro-alpha-2 (I) chain of type 1 precollagen (collagen), the osteoblast marker enzyme alkaline phosphatase (AP), and the osteoblast derived signaling factor (growth factor) transforming growth factor-beta (TGF beta). Radial growth at the tibial diaphysis achieved a maximum value in 8-wk-old rats and decreased progressively with age thereafter. This age-related decrease in the radial growth rate was initially due to reduced osteoblast activity; however, in older rats (greater than 17 wk old) reduced osteoblast number contributed to the decrease in bone formation. There was a strong correlation between the steady-state mRNA level for collagen and the periosteal bone formation rate. In contrast, the mRNA levels for the other bone proteins were more weakly correlated (TGF-beta and AP) or not correlated (BGP). These results suggest that the decreased bone matrix synthesis by periosteal cells in long bones of maturing rats is due to decreased expression of genes for bone matrix proteins. PMID- 1887883 TI - Sex-related differences in meprin-A, a membrane-bound mouse kidney proteinase. AB - To investigate the expression of meprin-A, a brush-border metalloproteinase in mouse tissues, immunohistochemical studies were conducted using a monoclonal antibody prepared against a purified form of kidney meprin-A form male mice. Kidney slices from female mice displayed markedly less immunoreactivity compared with similar preparations from male mice using this antibody. However, the specific activities of meprin-A in kidney homogenates and purified preparations of meprin-A from male and female mice were not significantly different. Western blots of kidney membrane proteins from several mouse strains indicated that the female form of meprin-A had a decreased mobility relative to the male form when subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis; this difference could be eliminated by treatment of preparations with endoglycosidase F, which removes some asparagine-linked oligosaccharides. These data and lectin blots of membrane proteins indicate that there are differences in the glycosylation (specifically in the complex type oligosaccharides) of meprin-A in adult (8 wk old) male and female mice. Juvenile (3 wk old) male and female mice displayed similar amounts of immunohistochemical staining in kidney slices, as well as similar meprin-A electrophoretic mobilities and lectin affinities. Administration of 17 beta-estradiol to gonadectomized adult mice decreased the immunoreactivity of meprin-A in kidney slices and the electrophoretic mobility of meprin-A. These studies indicate that estrogens affect posttranslational modifications of meprin-A. PMID- 1887884 TI - Insulin responsiveness of CK-M and CK-B mRNA in the diabetic rat heart. AB - Decreased cardiac performance is a known complication of diabetes mellitus, but the detailed molecular mechanisms that are responsible for this contractile abnormality are only incompletely explored, and cardiac gene products of known function, which are markedly and actively insulin responsive, have not been described. Recently, we found that creatine kinase (CK) enzyme activity and CK-M subunit mRNA levels are decreased in the heart of rats with experimental diabetes mellitus. These abnormalities could be restored to normal with chronic insulin administration. The CK-M and CK-B genes are expressed in the heart, and we wanted to determine whether diabetes also induces a change in CK-B mRNA levels. Quantitation of CK-M and CK-B mRNA levels on Northern blots with specific cDNA probes showed that, in diabetic hearts, CK-B mRNA levels represent only 19.8% of control levels and are more markedly depressed than CK-M mRNA levels, which are 46.5% of control values. Acute injection of insulin led to a significant 1.6-fold increase in CK-M mRNA and a 2.2-fold increase of CK-B mRNA 5 h after insulin injection. CK-M mRNA levels were restored to normal within 12 h, but 48 h were required to restore CK-B mRNA levels to normal values. After 1 mo of insulin therapy, CK-B mRNA levels had risen 9.7-fold, exceeding normal values by 90%, whereas CK-M mRNA levels were at the normal level as previously shown. CK enzyme activity showed only a small response to insulin administration 48 h postinjection. Diabetes leads therefore to a marked lowering of CK-M and CK-B mRNA levels in the rat heart.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1887885 TI - Maintenance of thyroid hormone production during exercise-induced weight loss. AB - Calorie restriction reduces thyroxine (T4) and 3,5,3'-triiodothyronine (T3) production, but the effects of exercise-induced weight loss on thyroid hormone metabolism in rodents are unclear. We studied the effects of chronic exercise on T4 and T3 metabolism comparing exercising (exercise) rats pair fed to sedentary (control) rodents and to weight-matched underfed sedentary animals (underfed; caloric intake 75% of ad libitum-fed controls). The exercise group utilized voluntary running wheels (28 days), and thyroid hormone metabolism was assessed using a three-compartment kinetics model. The exercise and underfed groups were equivalent in weight, but protein mass was greater in the exercise vs. underfed groups (30.4 +/- 0.5 vs. 27.9 +/- 0.5 g; P less than 0.05). During exercise, the T4 plasma clearance rate (PCR) was decreased (-39.2%; P less than 0.01) and the T4 concentration in serum was increased (48.6%; P less than 0.01), resulting in an unchanged T4 plasma appearance rate (PAR) vs. the control group. The decrease in T4 PCR in the exercise group was associated with a lower transport rate of T4 out of the slow pool (P less than 0.01). In the underfed group there was a reduction in both T4 serum concentration and PAR (-36%; P less than 0.01) compared with the control group, which was associated with a decrease in the volume of distribution (-25%; P less than 0.01). T3 PAR decreased 38.7% (P less than 0.01) during underfeeding but only 16.9% (P = not significant) during exercise vs. the control group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1887886 TI - Glucose availability and sensitivity to anoxia of isolated rat peroneal nerve. AB - The contrast between resistance to ischemia and ischemic lesions in peripheral nerves of diabetic patients was explored by in vitro experiments. Isolated and desheathed rat peroneal nerves were incubated in the following solutions with different glucose availability: 1) 25 mM glucose, 2) 2.5 mM glucose, and 3) 2.5 mM glucose plus 10 mM 2-deoxy-D-glucose. Additionally, the buffering power of all of these solutions was modified. Compound nerve action potential (CNAP), extracellular pH, and extracellular potassium activity (aKe) were measured simultaneously before, during, and after a period of 30 min of anoxia. An increase in glucose availability led to a slower decline in CNAP and to a smaller rise in aKe during anoxia. This resistance to anoxia was accompanied by an enhanced extracellular acidosis. Postanoxic recovery of CNAP was always complete in 25 mM HCO3(-)-buffered solutions. In 5 mM HCO3- and in HCO3(-)-free solutions, however, nerves incubated in 25 mM glucose did not recover functionally after anoxia, whereas nerves bathed in solutions 2 or 3 showed a complete restitution of CNAP. We conclude that high glucose availability and low PO2 in the combination with decreased buffering power and/or inhibition of HCO3(-)-dependent pH regulation mechanisms may damage peripheral mammalian nerves due to a pronounced intracellular acidosis. PMID- 1887887 TI - Jejunal mucosal injury and restitution: role of hydrolytic products of food digestion. AB - The effects of hydrolytic products of carbohydrate, protein, and lipid digestion on jejunal mucosal injury and restitution were assessed in anesthetized rats. Mucosal epithelial integrity was continuously monitored by measuring the blood-to lumen clearance of 51Cr-labeled EDTA. Perfusion of the lumen with hydrolyzed casein (3%) or glucose (150 mM) did not affect 51Cr-EDTA clearance compared with saline controls. By contrast, perfusion with emulsified lipids (20 mM sodium taurocholate and 10-40 mM oleic acid) increased 51Cr-EDTA clearance in a dose dependent manner. The lipid-induced increase in 51Cr-EDTA clearance returned toward control levels when the lipid infusion was terminated and saline perfusion resumed. Histological evaluation of jejunal mucosa indicated that the epithelial lining of the villous tips was damaged during lipid infusion and that restitution of the lining occurred within 50 min after resumption of saline perfusion. In vitro studies indicated that neither glucose nor hydrolyzed casein affected the integrity of rat intestinal epithelial cell (IEC-18) monolayers in culture. Oleic acid emulsified in rat hepatic bile produced a dose-dependent disruption of the epithelial monolayer. Biochemical determination of lipid peroxidation products in vivo and in vitro yielded negative results, indicating that the lipid-induced epithelial cell injury was not due to lipid peroxidation. Because the concentrations of the various nutrients used in the present study are similar to those measured in postprandial chyme, the findings of the present study suggest that the intestinal epithelium is injured and restitutes during the normal course of digestion and absorption of a meal. PMID- 1887888 TI - Nitric oxide: mediator of nonadrenergic noncholinergic responses of opossum esophageal muscle. AB - Nonadrenergic noncholinergic (NANC) nerves of the opossum esophagus mediate relaxation of circular muscle from the lower esophageal sphincter (LES) and the off contraction of circular esophageal muscle. The latencies between the end of the stimulus and the off contraction describe a gradient so that the latency is longest in muscle from the caudad esophagus. NG-nitro-L-arginine (L-NNA), an inhibitor of nitric oxide (NO) synthase, and NO were used to test the hypothesis whether NO is a mediator of these nerve-induced responses. Both electrical field stimulation (EFS) of intrinsic esophageal nerves and exogenous NO relaxed LES muscle. Only EFS-induced relaxation was inhibited by L-NNA [half-maximal response (EC50) = 60.0 +/- 20.0 microM]. L-Arginine, the substrate for NO synthase, reversed the inhibitory effect of L-NNA. Exogenous NO did not contact circular esophageal muscle. Both the amplitude (EC50 = 14.7 +/- 4.0 microM) and the latency of the off contraction (EC50 = 41.1 +/- 5.6 microM) were diminished by L NNA. L-Arginine prevented the action of L-NNA. NG-nitro-L-arginine also attenuated the gradient in the latency of the off response by shortening latencies in muscle from the caudad esophagus. It had no effect on cholinergic nerve-induced contraction of longitudinal esophageal muscle. These data support the hypothesis that NO or an NO-containing compound may be a mediator of NANC nerve-induced responses of the esophagus and LES. PMID- 1887889 TI - Electric properties of rat liver cell cultures on gas-permeable membranes. AB - In rat hepatocytes grown on gas-permeable membranes (Petzinger et al. In Vitro Cell. Dev. Biol. 24: 491-499, 1988), cellular and canalicular potentials as well as input resistances were measured using two-channel microelectrodes. In HCO3(-) containing solutions, we found -30.9 +/- 0.4 (SE) (n = 141) and -13.9 +/- 1.4 mV (n = 22) for cell and canalicular membrane potentials, respectively. There was no dependence of these parameters on the age of the primary culture. Canalicular input resistance, however, increased from 13.3 +/- 2.0 M omega (n = 4) at day 1 after seeding to 36.1 +/- 5.0 M omega (n = 9) at day 2 and stabilized thereafter, while cell input resistance continuously decreased from 37.0 +/- 3.3 M omega at 1 h (n = 6) to 5.2 +/- 2.1 M omega (n = 27) at 3 days after preparation. In ion substitution experiments there were no changes in the transference numbers for K+, Na+, or Cl- that could account for this effect. Cable analysis, however, revealed that the decrease in input resistance reflects a time-dependent increase in electrical coupling between cells. We conclude that rat liver cells on gas permeable membranes are highly suited for the quantitative analysis of cell-to cell interaction. In addition, cells and canaliculi are readily accessible with two-channel microelectrodes, making this preparation a promising tool for electrophysiological analysis of hepatocellular transport mechanisms. PMID- 1887890 TI - Effect of increased intra-abdominal pressure on peristalsis in feline esophagus. AB - Our aim in this study was to determine the effect of variations in intrabolus pressure on esophageal peristalsis. In five cats, intrabolus pressure was altered by increasing intragastric pressure to 20-45 mmHg by use of a pressure cuff to compress the abdomen. In each cat, increases in intragastric pressure were associated with comparable increases in pressure of the esophageal bolus while the bolus was in the distal esophagus during esophageal peristalsis. Secondary peristalsis induced by a 5-ml injection of barium into the proximal esophagus was recorded by synchronized videofluoroscopy and esophageal manometry. Graded increases in intrabolus pressure caused an increased prevalence of ineffective, incomplete peristaltic sequences that did not completely clear barium from the esophagus. At intragastric pressures greater than 45 mmHg, 63% of the peristaltic sequences were incomplete. Increases in intrabolus pressure elicited by increased intragastric pressure also caused 1) slowing of the peristaltic wave in the distal esophagus, 2) increased pressure wave duration in the distal esophagus, 3) increased esophageal diameter, and 4) increased duration of lower esophageal sphincter opening. The incidence of retrograde bolus escape was inversely related to the difference between peristaltic wave amplitude and intrabolus pressure. A pressure difference of greater than 20 mmHg prevented retrograde barium escape at all esophageal levels, whereas a difference of less than 20 mmHg was generally associated with retrograde escape of barium in the distal esophagus. We conclude that an increase in intrabolus pressure causes an increase in esophageal distension that is transduced into alterations of esophageal peristalsis by either a myogenic or neural mechanism. PMID- 1887891 TI - Comparison of fluid absorption by bovine and ovine descending colon in vitro. AB - Although bovine and ovine descending colon absorbed solute and sodium at approximately the same rate in vitro, water absorption by bovine colon was faster (15.0 +/- 2.0 microliters.h-1.cm-2, n = 8) than by ovine colon (8.6 +/- 1.3 microliters.h-1.cm-2, n = 9; P less than 0.01). Consequently, the observed osmolality of cattle absorbate was lower (364 +/- 13 mosmol/kg, n = 8) than with sheep (807 +/- 135 mosmol/kg, n = 9; P less than 0.01). Paracellular permselectivity was examined to elucidate this difference; the permeability of bovine descending colon to [3H]polyethylene glycol 400 and 4000 was higher than in sheep (P less than 0.001). A paracellular solvent drag was observed in bovine but not in ovine colon, and the electrical resistance of bovine colon was lower (16.0 +/- 1.4 omega.cm2) than ovine colon (28.0 +/- 2.4 omega.cm2; P less than 0.001). Pore radii of 2.5 nm for ovine and 5 nm for bovine colonic paracellular route were estimated from these data. It is concluded that an increased hydraulic conductance of the "active" route for solute absorption combined with raised solute reflux via the wider paracellular pathway may account for the failure of cattle to form a hypertonic absorbate and, consequently, hard feces. PMID- 1887892 TI - Mechanism of arachidonic acid transport across rabbit distal colonic mucosa. AB - The initial rate of [1-14C]arachidonic acid (AA) entry in the serosal side of rabbit distal colonic mucosa mounted in Ussing-type chambers is linear and independent of intracellular metabolism. When the maximal AA uptake was plotted as a function of medium AA concentration in ranges between 50 and 500 nM, saturation of the AA uptake with increasing concentrations was observed. The time course of the uptake of oleic acid and palmitic acid was similar to that observed with AA, and their separate addition to incubation medium strongly reduced the AA uptake. The influx of arachidonate was largely inhibited by ouabain and by incubation with mucosal sodium-free solution and amiloride, while it was increased when colonic mucosa was exposed to luminal amphotericin B. However, voltage-clamp studies showed that the AA entry rate appeared to be linearly related (r = 0.99) to transepithelial potential difference (PD) and suggested that the sodium dependence of AA translocation is an indirect effect of the changes in transepithelial PD induced by sodium transport shifts. These features provide evidence that there is a common entry pathway for AA and other long-chain free fatty acids mediated by a mechanism of facilitated diffusion driven by transmembrane PD. PMID- 1887893 TI - Inhibitory effect of ileal oleate on postprandial motility of the upper gut. AB - To determine the effect of ileal oleate on postprandial gastrointestinal motility, duodenal and paired perfusion-aspiration ileal catheters and bipolar duodenal and jejunal electrodes were surgically implanted in five dogs. The ileum was perfused with either saline or an isotonic oleic acid emulsion at 2 ml/min. A 205-kcal mixed meal containing 120 ml liquid nutrient labeled with 111In diethylenetriamine pentaacetic acid (DTPA) and solid food labeled with 99mTc was then administered orally. Gastric emptying was assessed by a gamma camera, myoelectric activity was continuously monitored, and duodenal-ileal transit of phenol red was determined over the ensuing 240 min. Ileal oleate reduced duodenal spikeburst frequency by 50% (P less than 0.05) and delayed gastric emptying of liquids and solids. Four hours after ingesting the meal, 62% of solids and 34% of liquids were retained in the stomach during oleic acid perfusion compared with 25 and 4%, respectively, when saline was perfused (P less than 0.05). Duodenal-ileal transit was markedly slowed by ileal perfusion with the oleic acid emulsion (P less than 0.001). Ileal oleate therefore exerted a profound inhibitory effect on proximal gut motility in the early period after ingestion of a mixed-nutrient meal in dogs. PMID- 1887894 TI - Role of oxygen-derived free radicals in indomethacin-induced gastric injury. AB - The role of oxygen-derived free radicals in the pathogenesis of acute gastric ulceration induced by indomethacin (Indo) was investigated in rats. Gastric damage was assessed by blood-to-lumen leakage of 51Cr-EDTA, as well as by measuring the extent of macroscopically visible hemorrhagic lesions. The stomach was perfused with isotonic saline for 30 min, followed by Indo (10 mg/ml for 30 min) and HCl (100 mM for 60 min). Rats were given a continuous intravenous infusion of the antioxidant enzymes superoxide dismutase (SOD) or catalase or the iron-chelating agent deferoxamine. Additional rats received an intravenous infusion of the vehicle (control group) or were pretreated with prostaglandin E2 (100 micrograms/kg ip) or allopurinol (50 mg/kg po). Exposure of the stomach to Indo caused a fourfold increase in 51Cr-EDTA leakage compared with that observed in rats receiving only the vehicle for Indo. Subsequent exposure of the stomach to HCl resulted in a further twofold increase in 51Cr-EDTA leakage. Treatment with SOD, catalase, or deferoxamine significantly (P less than 0.05) reduced 51Cr EDTA leakage during the intragastric perfusion with Indo and during the subsequent exposure to HCl. Pretreatment with PGE2 reduced 51Cr-EDTA leakage during perfusion with HCl only. Pretreatment with allopurinol did not significantly affect 51Cr-EDTA leakage at any time during the experiment. In addition to reducing the leakage of 51Cr-EDTA into the gastric lumen, SOD, catalase, and PGE2 significantly reduced the extent of macroscopically visible mucosal damage (P less than 0.05). These results support the hypothesis that oxygen-derived free radicals, probably derived from neutrophils, contribute to the pathogenesis of Indo-induced ulceration. PMID- 1887895 TI - Ischemia-reperfusion-induced mucosal dysfunction: role of neutrophils. AB - The ability of the small intestine to absorb and transport lipid into lymph is markedly reduced 24 h after a 10-min total occlusion of the superior mesenteric artery (SMA). The aim of this study was to define the role of neutrophils in the ischemia-reperfusion (I/R)-induced decrement in lipid absorption. A lipid test meal containing 40 mumol of radioactive triolein was infused intraduodenally at 3 ml/h for 8 h, and radioactive lipid output in lymph was monitored during lipid infusion in intestinal lymph fistula rats. Animals rendered neutropenic with antineutrophil serum (ANS) did not exhibit the reduction in lipid absorption and transport in lymph normally observed 24 h after I/R. This protective effect of ANS was specifically related to the reduction in the number of neutrophils in the intestinal mucosa. The amount of radioactive lipid detected in the liver of untreated rats was significantly higher than in control rats, suggesting an increased portal transport of infused radioactive lipid. Neutropenia reduced the liver lipid level toward the control value. The intestinal blood flow response to SMA occlusion was not altered by neutropenia. Our results suggest that neutrophils play an important role in the mucosal dysfunction associated with ischemia-reperfusion. PMID- 1887896 TI - Fatty acids stereospecifically stimulate neurotensin release and increase [Ca2+]i in enteric endocrine cells. AB - In primary cultures of canine enteric endocrine cells, fatty acids directly stimulated the release of neurotensin-like immunoreactivity (NTLI). This stimulatory effect was cell specific, selective for long-chain unsaturated fatty acids, and stereospecific. Saturated fatty acids of comparable chain length and trans isomers of long-chain unsaturated fatty acids had no effect on basal NTLI secretion. NTLI release in response to oleic acid (cis-11) was dose dependent with an apparent EC50 of 37 +/- 0.18 microM. Cyclooxygenase inhibitors had no effect on fatty acid-stimulated NTLI release, indicating the response was not mediated by the production of active arachidonic acid metabolites. Somatostatin (100 nM) inhibited maximal oleic acid-stimulated NTLI release by 92%. Long-chain unsaturated fatty acids also selectively and stereospecifically stimulated an increase in the mobilization of [Ca2+]i to 313.5 +/- 28.6% of resting [Ca2+]i. Staurosporine, an inhibitor of protein kinase C, dose dependently inhibited oleic acid-stimulated NTLI release with an IC50 value of 22 +/- 0.4 nM. Long-chain unsaturated fatty acids had no effect on basal NTLI secretion from rat pheochromocytoma cells and medullary thyroid carcinoma cells, two clonal lines that express NTLI. The cell-specific, selective stereospecific, and inhibitable action of fatty acids on NTLI secretion suggests that the effect of fatty acids on enteric endocrine cells is indicative of a receptor-mediated mechanism. PMID- 1887897 TI - Cl(-)-HCO3- exchanger in isolated rat hepatocytes: role in regulation of intracellular pH. AB - In rat hepatocytes, basolateral Na(+)-H+ exchange and Na(+)-HCO3- cotransport function as acid extruders. To assess mechanisms of acid loading, intracellular pH (pHi) recovery from an alkaline load was analyzed in short-term cultured rat hepatocyte monolayers using the pH-sensitive dye BCECF. Electrophysiological techniques were also used to assess the role of the membrane potential (Vm). Cells were alkaline loaded by suddenly reducing external CO2 and HCO3- (from 10% and 50 mM, respectively, to 5% and 25 mM) at constant pHo. After this maneuver, pHi rapidly rose by 0.13 +/- 0.03 pH units (pHu) and recovered to baseline at an initial rate of 0.026 +/- 0.009 pHu/min. Intracellular buffering power was estimated from the dependence of pHi on [NH4+]o and varied between 70 and 10.5 mM/pHu in a pHi range of 6.5-7.6. Initial pHi recovery corresponded to a rate of OH- efflux (JOH) of 1.76 +/- 0.71 mM/min and was blocked by 0.5 mM DIDS (0.003 +/ 0.002; JOH = 0.18 +/- 0.06) or by 1 mM H2DIDS (0.001 +/- 0.002; JOH = 0.26 +/- 0.08) and by removal of [Cl-]o (0.003 +/- 0.007; JOH = 0.28 +/- 0.07). The dependence of JOH on [Cl-]o exhibited saturation kinetics with an apparent Km for [Cl-]o of 5.1 mM. pHi recovery was Na+ independent and was not inhibited by substitution of Na+ with NMDG (0.045 +/- 0.09; JOH = 2.94 +/- 0.59). During an alkaline load, cell Vm hyperpolarized from -33.4 +/- 1.8 to -43.4 +/- 2.8 mV, mainly due to an increase in K+ conductance by a factor of 2.8 +/- 0.3.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1887898 TI - Ornithine decarboxylase is involved in repair of small intestine after ischemia reperfusion in rats. AB - To assess whether ornithine decarboxylase (ODC) is involved in mucosal repair after ischemia-reperfusion (I/R), two approaches were used: 1) measurement of mucosal ODC activity at different intervals after I/R, and 2) inhibition of ODC activity with alpha-difluoromethylornithine (DFMO, an irreversible inhibitor). In the first series of experiments, rats were allowed to recover after superior mesenteric arterial occlusion (10 min) before harvesting the intestinal mucosa for measurement of ODC activity. ODC activity increased markedly 6 h after I/R, and greater than 72 h were required for enzyme activity to return to normal. DFMO treatment completely abolished the I/R-induced increase in ODC activity. In another series of experiments, rats with an intestinal lymph fistula were infused intraduodenally at 3 ml/h with vehicle or 2% DFMO in vehicle immediately after I/R. Lipid absorption was measured at 24 and 48 h after I/R. In the DFMO group, lymph radioactive lipid output at 24 h after I/R was significantly lower compared with time-matched sham-operated controls. Lymph lipid output in rats receiving the vehicle was restored to a normal level at 48 h after I/R. However, this restoration of normal lymphatic lipid transport at 48 h I/R was not observed in the DFMO group. These observations indicate that ODC activity plays an important role in the repair process that results in complete restoration of mucosal function 2 days after I/R. PMID- 1887899 TI - Portal transport of absorbed lipids in rats. AB - Previous studies [C. M. Mansbach II and A. Arnold. Am. J. Physiol. 251 (Gastrointest. Liver Physiol. 14): G263-G269, 1986] have shown that only 41% of the mass and 54% of the disintegrations per minute (dpm) are recovered in lymph on duodenal infusion of 3H-labeled glyceryl trioleate (TO). The present studies evaluate the potential that the unaccounted for lipids were transported via the protal vein. Rats received portal vein, carotid artery (surrogate for the mesenteric artery), and duodenal cannulas and an ultrasonic flow probe around the portal vein. [3H]TO (135 mumol/h) was infused into the duodenum, and blood samples were collected from the other cannulas. Portal flow was recorded. Portal fatty acid (FA) increased from 220 to 705 nmol/ml during the 6-h infusion and was 201 mumol/h in excess in the portal vein vs. the carotid artery. All common FAs were increased in the portal vein vs. the carotid artery except C18:3 and C20:4. Thirty-nine percent of the dpm infused was calculated to be transported via the portal vein. We conclude that considerable endogenous FA and infused lipid, mostly as triacylglycerol, are transported in the portal vein in response to TO infusion. We speculate that TO infusion induces endogenous FA mobilization from the mesenteric bed. PMID- 1887900 TI - Hepatic venular pressures of rats, dogs, and rabbits. AB - We tested the hypotheses that the hepatic venule pressures (Phv), just downstream from the hepatic sinusoids, are closely similar (less than 2 mmHg) either to the portal venous pressure (Ppv), indicating a high hepatic venous resistance, or to the inferior vena cava (Pivc) pressure, indicating a high portal-sinusoidal venous resistance, as reported by previous investigators. A micropipette servo null pressure measurement technique was used with rats, dogs, and rabbits. Phv, referred to the anatomic level of the vena cava, averaged 5.1 +/- 1.0, 6.4 +/- 1.1, and 5.4 +/- 1.0 (SD) mmHg in the rats, puppies, and rabbits, respectively. Ppv averaged 8.0 +/- 1.4, 10.8 +/- 2.2, and 7.4 +/- 1.5 mmHg, respectively. Norepinephrine infusion into the portal vein (1-5 micrograms.min-1.kg-1) caused Ppv to increase and the portal venous flow to decrease but did not significantly affect Phv. The hepatic venous circuit contributed 44 +/- 17% (rats) and 31 +/- 26% (dogs) of the total liver venous vascular resistance under control conditions. We conclude that the portal and sinusoidal vasculatures are the dominant, but not exclusive, resistance sites of the liver venous vasculature both at rest and during norepinephrine-induced vasoconstriction. PMID- 1887901 TI - In vivo measurement of rat gastric surface cell intracellular pH. AB - Intracellular pH (pHi) of the surface mucous cells of the rat stomach was measured in vivo using a fluorescent microscopic technique. Gastric surface mucous cells were loaded with fluorescein by superfusion with 5(6)-carboxy fluorescein diacetate, and the ratio of the intensity of emitted fluorescence at 495 and 450 nm excitation was determined by image analysis of videotapes. An in vivo calibration curve was constructed using 10(-5) M nigericin to equilibrate pHi and extracellular pH, and intra- and extracellular potassium concentrations. The pHi of the gastric surface cells was 7.22 +/- 0.06, and pHi was stable over 45 min. A pulse of 20 mM NH4Cl in Krebs solution rapidly alkalinized the cells to pH 7.7, followed by a slow return of pHi to baseline pH 7.2. After withdrawal of NH4Cl, pHi dropped to 6.7 with gradual recovery to baseline. pHi increased when the mucosa was superfused, in the presence of nigericin, with 150 mM KCl solutions and decreased when superfused with 2.6 mM KCl solutions. Perfusing with pH 3 Krebs buffers transiently decreased pHi, whereas superfusion with pH 1.2 Krebs irreversibly decreased pHi. These findings confirm that the measured fluorescence was intracellular and that the cells responded to changes in luminal pH. PMID- 1887902 TI - Functional characterization of alpha- and beta-intercalated cell types in rabbit cortical collecting duct. AB - Single-cell electrical measurements and spectrophotometric determinations of intracellular pH were used to determine unique features of alpha- and beta intercalated cells (alpha-IC, beta-IC) in in vitro perfused rabbit cortical collecting ducts (CCD). pHi rose in alpha-IC and fell in beta-IC after bath Cl- removal. Luminal Cl- removal did not change pHi of alpha-IC, but pHi of beta-IC rose by 0.36 +/- 0.01 pH units. Cl- concentration-dependent recovery of beta-IC pHi revealed a Cl- Km of 18.7 mM for the luminal Cl(-) -HCO3- exchanger. Measurements of basolateral membrane voltage (Vbl) also showed two IC cell types. Removal of luminal Cl- did not change Vbl in alpha-IC, whereas Vbl hyperpolarized by a mean of 73.2 +/- 3.5 mV in beta-IC. Reducing bath Cl- depolarized both alpha and beta-IC Vbl. In alpha-IC a large repolarization of 39.8 +/- 5.2 mV followed acute depolarization after bath Cl- removal. Reducing bath HCO3- (constant CO2) had little effect on beta-IC Vbl, whereas alpha-IC Vbl depolarized by 5.2 +/- 0.7 mV. Reducing luminal HCO3- in the absence of luminal Cl- produced a 17.6 +/- 1.8 mV depolarization in beta-IC. This change was independent of luminal Na+ and was not blocked by luminal 10(-4) M 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS). In beta-IC, Vbl was not altered by either bath or lumen DIDS in the presence of luminal Cl-. However, when luminal Cl- was removed, luminal DIDS reversibly depolarized Vbl by 9.6 +/- 2.9 mV.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1887904 TI - Chaos in blood flow control in genetic and renovascular hypertensive rats. AB - Hydrostatic pressure and flow in renal proximal tubules oscillate at 30-40 mHz in normotensive rats anesthetized with halothane. The oscillations originate in tubuloglomerular feedback, a mechanism that provides local blood flow regulation. Instead of oscillations, spontaneously hypertensive rats (SHR) have aperiodic tubular pressure fluctuations; the pattern is suggestive of deterministic chaos. Normal rats made hypertensive by clipping one renal artery had similar aperiodic tubular pressure fluctuations in the unclipped kidney, and the fraction of rats with irregular fluctuations increased with time after the application of the renal artery clip. Statistical measures of deterministic chaos were applied to tubular pressure data. The correlation dimension, a measure of the dimension of the phase space attractor generating the time series, indicated the presence of a low-dimension strange attractor, and the largest Lyapunov exponent, a measure of the rate of divergence in phase space, was positive, indicating sensitivity to initial conditions. These time series therefore satisfy two criteria of deterministic chaos. The measures were the same in SHR as in rats with renovascular hypertension. Since two different models of hypertension displayed similar dynamics, we suggest that chaotic behavior is a common feature of renal vascular control in the natural history of the disease. PMID- 1887903 TI - Basolateral tetraethylammonium transport in intact tubules: specificity and trans stimulation. AB - To examine the specificity of proximal renal basolateral organic cation transport, the effects of unlabeled organic cation substrates in the bathing medium on the rate of uptake [14C]tetraethylammonium ([14C]TEA) by intact nonperfused proximal tubules and isolated basolateral membrane vesicles (BLMV) from rabbit kidneys were explored. The pattern of inhibition of transport by a battery of unlabeled organic cations was similar in intact tubules and BLMV. To determine if trans-stimulation could be demonstrated across the basolateral membrane of intact tubules, the effects of preloading tubules with unlabeled substrates on the rate of uptake of [14C]TEA and the effects of unlabeled substrates in the bathing medium on the rate of efflux of [14C]TEA from tubules preloaded with this labeled substrate were examined. Trans-stimulation was clearly demonstrated for the first time in intact tubules. However, of the compounds that significantly inhibited [14C]TEA uptake (TEA, amiloride, tetrapropylammonium, mepiperphenidol, isopropyl pyridinium, and choline), only TEA itself and choline produced a trans-stimulation of [14C]TEA uptake. Moreover, choline appeared to be at least as effective as TEA itself as a counter ion for TEA transport. Such trans-stimulation could play a physiological role in the net reabsorption of choline and the net secretion of most other organic cations. PMID- 1887905 TI - Analysis of pulsatile pressures and flows in glomerular filtration. AB - Previous mathematical models of glomerular filtration have ignored the pulsatility of the glomerular capillary pressure, using only steady-state equations and time-averaged pressures and flows. Because the actual pressure pulses are rapid and of large amplitude and because the governing equations are nonlinear, it is questionable whether the effects of the pressure pulses average out in the manner that has been assumed. We have developed a model that includes sinusoidal variations in the glomerular transcapillary hydraulic pressure (delta P) and the afferent arteriolar plasma flow rate over each cardiac cycle. The analysis suggests that the previously ignored time derivatives in the luminal mass balance equations are not negligible. The amplitude of the oscillations in delta P was found to be sufficient to reverse the direction of the transmural fluxes over part of each cardiac cycle, at the more efferent locations in a capillary. However, the time-averaged values of single-nephron glomerular filtration rate and sieving coefficients for macro-molecules from the pulsatile model differed from that for a steady-state formulation by less than 0.1 and less than or equal to 10%, respectively. We conclude that use of the usual steady state assumption introduces negligible errors in calculating glomerular membrane parameters from experimental data. PMID- 1887906 TI - Polyclonal antibodies in study of ADH-induced water channels in frog urinary bladder. AB - It is now generally accepted that changes in water permeability in anti-diuretic hormone (ADH)-responsive target epithelial cells result from the insertion in the plasma apical membrane of new components that contain channels for water. The specificity of these channels suggests that they are formed by intrinsic proteins having access to both facies and spanning the whole membrane. We have previously shown that Triton X-100 apical extracts from ADH-stimulated frog urinary bladder contain some proteins inserted under hormonal stimulation. In the present study we have developed polyclonal antibodies using Triton X-100 extract as an immunogen. After considering the inhibitory effect exerted by the whole immune serum on the osmotic water flow, we used different adsorption steps to select, from the immune serum, antibodies to apical membrane proteins inserted in response to the hormone. Immunoblot analysis of these selected antibodies shows that they recognize seven to eight proteins, of which 55-, 35-, 26-, and 17-kDa proteins are always present. Antibodies to these four proteins, affinity purified on nitrocellulose sheets, inhibited ADH-induced osmotic water flow. Altogether these results strongly suggest that proteins of 55, 35, 26, and 17 kDa (or at least one of them) are likely to be involved in the mechanism of water transport. PMID- 1887907 TI - Glomerular hypertrophy accelerates hypertensive glomerular injury in rats. AB - Micropuncture and morphological studies were performed in four groups of rats that received subcutaneous infusions of saline or angiotensin II (ANG II) for 8 wk. Group 1 rats received saline; group 2 rats were subjected to uninephrectomy and then received saline; group 3 rats received ANG II (100 ng/min); and group 4 rats were subjected to uninephrectomy and then received ANG II (50 ng/min). In comparison with group 1 rats, group 2 rats exhibited no increase in mean arterial pressure (MAP) (group 2, 102 +/- 6 mmHg; group 1, 104 +/- 10 mmHg) or glomerular capillary pressure (PGC) (group 2, 56 +/- 3 mmHg; group 1, 55 +/- 4 mmHg). In the absence of glomerular hypertension, an increase in glomerular volume (VG) was not associated with glomerular sclerosis in group 2 rats. In contrast to group 2 rats, group 3 rats exhibited increases in MAP (161 +/- 13 mmHg) and PGC (70 +/- 7 mmHg) without any increase in VG. Glomerular hypertension was associated with development of increased albuminuria and glomerular sclerosis in group 3. Group 4 rats exhibited increases in MAP (157 +/- 18 mmHg), PGC (69 +/- 6 mmHg), and VG. These rats also developed glomerular sclerosis and significantly more albuminuria than would have been expected from simple combination of effects of uninephrectomy and ANG II infusion. Additional morphological studies were performed in two groups of rats that received ANG II for 12 wk. Over this period, uninephrectomized group 6 rats infused with ANG II (50 ng/min) developed markedly greater albuminuria and glomerular sclerosis than intact group 5 rats infused with ANG II (100 ng/min).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1887908 TI - Abnormal intestinal regulation of calbindin-D9K and calmodulin by dietary calcium in genetic hypertension. AB - Using isolated duodenal cells from spontaneously hypertensive rats (SHR) and their normotensive controls, Wistar-Kyoto rats (WKY), we previously showed that cellular calcium flux was decreased in SHR and that increasing dietary calcium (from 1 to 2%) eliminated strain differences in Ca2+ fluxes. The present study was carried out to investigate the role of calbindin-D9K and calmodulin in the flux difference and dietary calcium effects. Calbindin-D9K and calmodulin were separated by sodium dodecyl sulfate (SDS) gel electrophoresis in duodenal protein extracts of SHR and WKY (12-14 and 24-26 wk old) fed either a 1 or 2% calcium diet and measured by a ligand blotting (45Ca) technique. Young SHR had a significantly lower calbindin-D9K (P less than 0.001) than did WKY on either diet. Calmodulin was significantly lower in young SHR than in WKY (P less than 0.002). There was no strain difference in calmodulin in older rats fed the normal calcium diet. Calbindin-D9K was significantly decreased by the high-calcium diet in both strains at both ages. There was a significant correlation between duodenal calbindin-D9K and plasma levels of calcitriol (r = +0.80, P less than 0.001) in WKY but not in SHR. Calmodulin was significantly decreased by dietary calcium in mature WKY (4.8 +/- 0.2 vs. 3.7 +/- 0.4 micrograms/mg cell protein, P less than 0.03), demonstrating a potential regulation by dietary calcium of this protein. Finally, there was a significant correlation between calbindin-D9K and calmodulin (r = 0.59, P less than 0.001) in WKY but not in SHR.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1887909 TI - Pathways of acute pH regulation of ammoniagenesis in LLC-PK1 cells: study with [15N]glutamine. AB - The present study utilized [15N]glutamine labeled at amide (5-N) and amino (2-N) groups to analyze the metabolic fate of glutamine nitrogen in basal and in acute pH regulation of ammoniagenesis. One-hour incubation of LLC-PK1 cultures in a media of pH 7.4, 7.0, or 7.6 containing either [5-15N]glutamine or [2 15N]glutamine resulted in parallel alterations in glutamine consumption in response to acute acid-base maneuvers. Incubation with [5-15N]glutamine resulted in substantial enrichment and production of ammonia at pH 7.4, which was unaffected by the changes in media pH, and in no significant enrichment of alanine, aspartate, and glutamate. In contrast, significant enrichment and production of 15N-labeled ammonia, alanine, aspartate, and glutamate were detected from cultures incubated with [2-15N]glutamine. Ammonia formation, from incubation with [2-15N]glutamine, was stimulated significantly by a low pH and inhibited by high pH. Alanine production was altered in a fashion similar to ammonia formation, whereas aspartate production was unaltered and glutamate formation significantly decreased by a low pH. Furthermore, a low pH significantly increased the production of alpha-ketoglutaramate in a fashion qualitatively similar to alanine production. In contrast to our prior conclusions based on total metabolite production, these studies indicate that although ammonia formation at pH 7.4 is predominantly generated from the mitochondrial phosphate-dependent glutaminase pathway, the increased ammonia formation in acute acidosis is a result of increased flux through glutamate dehydrogenase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1887910 TI - Thromboxane stimulates synthesis of extracellular matrix proteins in vitro. AB - The vasoconstrictor eicosanoid thromboxane plays an important role in the pathogenesis of several renal diseases. As an autacoid, its local release alters blood flow and induces platelet aggregation. We report a direct stimulatory effect of thromboxane on extracellular matrix protein production and gene expression in vitro. Treatment of two cell types, differentiated mouse teratocarcinoma cells (F9+) and human glomerular mesangial cells, with two different thromboxane analogues resulted in increased production of components of the extracellular matrix including fibronectin and the basement membrane proteins laminin and type IV collagen. These responses to thromboxane were not the result of a mitogenic effect of thromboxane nor the result of an increase in total cellular protein. The increased production of extracellular matrix proteins was, at least in part, due to an increase in the steady-state level of mRNA for these genes. Furthermore, the effect of thromboxane was markedly inhibited by cotreatment with a thromboxane-receptor antagonist. These results suggest a new potential role for thromboxane as a mediator of the sclerotic and fibrotic responses to injury. PMID- 1887911 TI - Transport of sodium chloride and water in rat ascending vasa recta. AB - Experiments were undertaken to test the hypothesis that transcapillary small solute (NaCl and urea) gradients drive water across ascending vasa recta (AVR). Axial gradients of NaCl and urea were eliminated with furosemide. AVR were perfused with buffer containing fluorescein isothiocyanate-labeled dextran and 22Na. Perfusion of AVR with isotonic buffer at 10 and 20 nl/min yielded collectate-to-perfusate 22Na ratios of 0.17 +/- 0.05 and 0.34 +/- 0.03, respectively, in AVR of 601 +/- 56 and 583 +/- 46 microns mean length, respectively. A 22Na permeability of 113.2 +/- 12.8 x 10(-5) cm/s was determined. AVR were perfused at 20 nl/min with buffer NaCl of 0 (hypotonic to papilla), 161 (isotonic), or 500 mM (hypertonic). Transcapillary volume flux was not significantly different in these groups (3.8 +/- 1.5, 4.6 +/- 1.5, and 2.1 +/- 1.4 nl.min-1.mm-1, respectively). AVR were perfused in the hydropenic kidney at 5 nl/min antegrade from tip to base and retrograde from base to tip, which was a maneuver designed to impose physiological transcapillary NaCl and urea gradients of opposite direction. Volume fluxes were -1.4 +/- 0.05 and -1.3 +/- 0.04 nl.min 1.mm-1 in these groups, respectively. These data demonstrate that the AVR are highly permeable to NaCl and that physiological small solute gradients do not influence water movement across the AVR wall. PMID- 1887912 TI - Intracellular milieu changes associated with hypoxia impair sarcoplasmic reticulum Ca2+ transport in cardiac muscle. AB - The effects on sarcoplasmic reticulum (SR) Ca2+ transport of solutions mimicking the important intracellular milieu changes associated with short-term hypoxia (hypoxic solutions, as described by Kammermeier et al. J. Mol. Cell. Cardiol. 14: 267, 1982) were examined. SR Ca2+ content was estimated by measuring the magnitude of the caffeine-induced contracture in saponin-skinned rat papillary muscle. SR Ca2+ uptake was inhibited by hypoxic solutions only at loading times less than or equal to 30 s. This inhibition was primarily due to the increase in Pi. The hypoxic solutions had no effect on Ca(2+)-induced Ca2+ release from the SR. We also tested the effects of ATP-free (rigor) solutions that mimic the intracellular environment during late hypoxia and ischemia. Elevating Pi or ADP alone in rigor solution had no effect on SR Ca2+ content. However, elevating Pi and ADP (+/-Mg2+) produced a 44-48% reduction in SR Ca2+ content. This reduction is most likely due to reversal of the SR Ca2+ pump. We conclude that the changes in milieu with short-term hypoxia can depress contractility in intact cardiac muscle by inhibiting SR Ca2+ uptake. During long-term hypoxia or ischemia, these milieu changes can elevate intracellular Ca2+ by reversing the SR Ca2+ pump. PMID- 1887913 TI - Correlation between antioxidant changes during hypoxia and recovery on reoxygenation. AB - Changes in myocardial antioxidants due to different durations of hypoxia at normal or lower temperatures were correlated with the recovery of structure and function on reoxygenation. Hearts perfused with substrate-free hypoxic buffer at 37 degrees C for 5 or 10 min and at 22 degrees C for 10 min showed a significant depression in the contractile function and rise in resting tension. Reoxygenation of these hearts at 37 degrees C for 20 min resulted in a recovery of these functions. On reoxygenation, hearts made hypoxic for 10 min at 37 degrees C showed poor recovery of the contractile function, increase in malondialdehyde content and a dramatic increase in the creatine phosphokinase activity in the coronary effluent. Addition of catalase to the perfusion medium markedly improved function recovery of these hearts. Hypoxia at 37 degrees C for 5 min or at 22 degrees C for 10 min with or without reoxygenation had no effect on superoxide dismutase (SOD) or glutathione peroxidase (GSHPx) activities. These antioxidants were depressed in hearts made hypoxic for 10 min at 37 degrees C with no further change on reoxygenation. Neither SOD nor GSHPx was detected in the coronary effluent during hypoxia or reoxygenation. Hypoxia at 37 or 22 degrees C for 10 min caused significant ultrastructural changes, and on reoxygenation 37 degrees C hypoxic hearts showed exacerbation, whereas the 22 degrees C hypoxic hearts showed recovery. These data support the hypothesis that reduced antioxidant reserve during hypoxia may contribute to the oxidative injury on reoxygenation, suggesting that maintenance of endogenous antioxidant levels during hypoxia may be important for recovery. PMID- 1887914 TI - Turbulent pressure fluctuations on surface of model vascular stenoses. AB - Turbulence frequently develops when blood passes through a stenosis. To study the hypothesis that turbulence near a plaque surface can cause pressure fluctuations that may promote plaque rupture, models of intravascular stenoses were studied. Experimental conditions simulated peak flow in the coronary and carotid arteries through a stenosis of 80 or 90% diameter reduction and into a region where the plaque had widened distally to a 50-75% stenosis. For symmetric stenoses at carotid artery flow rates, peak pressure fluctuations were observed 1-1.5 upstream diameters distal to the stenosis, but there were no significant turbulent pressure fluctuations at coronary artery flow rates. Stenosis asymmetry strongly increased the intensity of turbulent pressure fluctuations at flows simulating carotid flow and resulted in significant pressure fluctuations for coronary flow conditions. Increasing stenosis severity from 80 to 90% increased the root mean square pressure fluctuations 3.6-fold. These studies predict peak to peak pressure fluctuations of 15 mmHg in a 90% asymmetric coronary stenosis; it is possible that turbulence may play a role in acute damage of atherosclerotic plaques, particularly in asymmetric stenoses. PMID- 1887915 TI - Adenosine inhibits postischemic leukocyte-endothelium interaction in postcapillary venules of the hamster. AB - The reduction of postischemic reperfusion injury by exogenous adenosine has been ascribed to reduced oxygen radical generation and adhesion of leukocytes to the vascular endothelium. To provide in vivo evidence for this concept we investigated the effects of adenosine (110 micrograms.kg-1.min-1 iv) on postischemic leukocyte-endothelium interaction in the dorsal skinfold chamber model in awake hamsters by intravital fluorescence microscopy. Leukocytes were stained in vivo with acridine orange and classified according to their interaction with the endothelium as nonadherent, rolling, or sticking leukocytes. In control animals, reperfusion after a 4-h pressure-induced ischemia to the striated muscle in the dorsal skinfold chamber elicited a marked increase in leukocyte rolling and sticking. This phenomenon was significantly attenuated in adenosine-treated animals 30 min after reperfusion. Postischemic changes in vessel diameters and red cell velocities were not affected by adenosine. The data suggest that systemic adenosine administration reduces reperfusion injury by the inhibition of postischemic leukocyte adherence to the microvascular endothelium. PMID- 1887916 TI - Characterization of AT2 angiotensin II receptors in rat anterior cerebral arteries. AB - Quantitative autoradiography using the agonist 125I-Sar1-angiotensin II was used to localize and characterize angiotensin II (AT) receptors in the anterior cerebral artery of the male rat. This artery showed a moderately high number of AT receptors, localized throughout the arterial wall. The number of receptors was higher (125 +/- 7 fmol/mg protein) in arteries from young 2-wk-old rats compared with those in adult 8-wk-old rats (43 +/- 2 fmol/mg protein). In the anterior cerebral artery, AT binding was insensitive to displacement with the selective AT1 antagonist DuP 753 but was readily displaced by the selective AT2 antagonist CGP-42112 A (concentration eliciting 50% of maximum inhibition: 6 +/- 1 x 10(-10) M). This indicated that the AT receptors in the cerebral artery were of the AT2 subtype. Our observations suggest that AT may exert its effects on cerebral circulation by stimulation of AT2 receptors and that these receptors may play a role during cerebrovascular development. PMID- 1887917 TI - Load-dependent left ventricular relaxation in conscious dogs. AB - Load-dependent relaxation was studied in eight conscious dogs by inflating an intra-aortic balloon during late systole. Initially, the balloon was inflated at the aortic dicrotic notch and deflated before the next systole; subsequently, the inflation time was moved progressively earlier in 30-ms steps. This intervention produced an abrupt increment in left ventricular (LV) systolic pressure. The contraction duration was assessed by measuring the time required for LV pressure to fall by 50% of its maximum value (P50). The rate of LV pressure decline was assessed by measuring its peak negative first time derivative (-dP/dt) and the time constant of relaxation (tau). When the balloon was inflated during late systole (50 +/- 5 ms before aortic dicrotic notch), the time to peak -dP/dt fell, P50 fell, peak -dP/dt increased, and tau was unchanged. Thus the initial rate of LV pressure decline was accelerated, and the duration of the contraction was abbreviated. These data indicated that myocardial relaxation in the intact conscious dog is load dependent. Late systolic balloon inflations were performed after treatment with propranolol, verapamil, or caffeine. During propranolol and verapamil, the rate of LV relaxation (peak -dP/dt and tau) was slowed; however, the effects of balloon inflation on LV pressure transients were qualitatively similar to that seen in the baseline state. By contrast, caffeine prevented the abbreviation in the contraction duration caused by late-systolic balloon inflation. Thus LV relaxation remained load dependent when myocardial relaxation was slowed by propranolol or verapamil; load-dependent relaxation was attenuated by caffeine, presumably due to its influence on the sarcoplasmic reticulum. PMID- 1887918 TI - Does pentobarbital anesthesia depress left ventricular contractility in dogs? AB - Although pentobarbital sodium (NP) anesthesia has been shown to depress left ventricular (LV) contractility in dogs, measurements of LV contractility in previous studies have been made soon after a bolus of NP was given when serum concentrations would be extremely high. In this study, we compared indexes of LV contractility during awake and anesthetized conditions. During anesthesia, measurements were obtained 1 h after an intravenous bolus of NP was given when serum concentrations were approximately 25 mg/l and above that reported to abolish pain. In 13 dogs, subendocardial ultrasonic crystal transducers and a high-fidelity pressure transducer were implanted into the LV. Measurements were obtained with and without prior treatment with propranolol to produce beta adrenergic blockade. LV contractility was assessed by ejection fraction and the end-systolic pressure-volume relationship. The effect of NP on ventricular myocardium was also examined in an in vitro canine right trabecular preparation to compare in vivo and in vitro effects. In the in vivo study, the results showed no decrease in LV contractility during anesthesia regardless of whether propranolol was administered. The in vitro preparation showed only a minimal decrease in isometric tension at the concentrations used in the in vivo study. We conclude that NP anesthesia does not depress LV contractility when concentrations are maintained at approximately 25 mg/l. PMID- 1887919 TI - Cerebrovascular effects produced by electrical stimulation of fastigial nucleus. AB - We used the microsphere technique and laser flowmetry to assess cerebral blood flow in 43 anesthetized rats. Cerebral blood flow did not increase significantly when the fastigial nucleus was stimulated 15 min after administration of alpha chloralose. In animals that received maintenance doses of alpha-chloralose, the modest (50%) increase in cerebral blood flow that did occur returned toward control during stimulation despite a continued stable elevation of arterial pressure. Stimulation of fastigial nucleus 2 h after alpha-chloralose elicited a 20 +/- 3 mmHg increase in arterial pressure; cerebral blood flow increased gradually for 30-60 s after the rise in arterial pressure and reached a peak that was approximately 90% (P less than 0.05) above baseline. The stimuli did not significantly reduce vascular resistance or impair autoregulation. We did not stimulate the fastigial nucleus for more than 2 h after administration of alpha chloralose because anesthesia was effective for only 2 h. This study demonstrates that stimulation of the fastigial nucleus in rat produces a delayed increase in cerebral blood flow that is blocked by alpha-chloralose anesthesia. The delay in increases of cerebral blood flow suggests that a metabolic mechanism, not a direct neurogenic vascular effect, may account for increases in flow with fastigial stimulation. PMID- 1887920 TI - Analysis of lymphatic protein flux data. V. Unique PS products and sigma dS at low lymph flows. AB - The selectivity of the capillary membrane to protein (osmotic reflection coefficient, sigma d) can be measured at high transcapillary volume flow when the capillary membrane can be considered as a true sieve. However, the diffusive capacity of the membrane (permeability-surface area product, PS) for macromolecules has not been directly measured, only estimated by assuming that transcapillary volume flow was zero. Based on unique properties of the Peclet number, a parameter that describes the ratio of solute convective flux relative to diffusive capacity, we have developed three new techniques using lymph protein fluxes to estimate a unique PS product that is independent of transcapillary fluid flux. Two of these techniques require a measure of sigma d when the ratio of protein concentration in lymph relative to plasma is equal to (1- sigma d), which occurs at high capillary filtration rates. However, the third method allows both sigma d and the PS product to be determined at relatively low lymph flow rates, eliminating the need for high capillary pressures to determine sigma d. For each protein, these techniques yield an estimate of PS and sigma d for the total membrane. However, by analysis of several different sized proteins and estimation of small- and large-pore volume flows, sigma d and PS can be determined separately for the small- and large-pore pathways. These techniques for estimating sigma d and PS were evaluated by modeling the total solute flux of albumin and immunoglobulins G and M in a heteroporous membrane. PMID- 1887921 TI - Influence of metabolic substrate on rat heart function and metabolism at different coronary flows. AB - The influence of metabolic substrate on contractile strength, myocardial oxygen consumption (MVO2), high- and low-energy phosphate levels, and intracellular pH were determined in isovolumically contracting isolated rat hearts perfused with solutions containing either glucose or hexanoate at both high and low coronary perfusion pressures (CPP). Contractile strength was not significantly influenced by substrate at a CPP of 80 mmHg. As coronary flow was decreased, developed pressure measured at a fixed left ventricular volume (LVV) was lower during hexanoate than glucose perfusion. The relationship between MVO2 and mechanical work determined at a CPP of 80 mmHg over a range of LVVs was shifted upward in a parallel manner when substrate was switched from glucose to hexanoate. The MVO2 work relationship measured at a fixed LVV but over a range of coronary flows (7 20 ml/min) was also parallel shifted upward on switching from glucose to hexanoate. Basal MVO2 was greater during hexanoate than glucose perfusion by an amount that accounted for two-thirds the total increase in MVO2 observed between the substrates under unloaded beating conditions. The remainder of the difference was attributed to increased energy requirements for excitation-contraction coupling. Inorganic phosphate concentrations increased more and phosphocreatine concentrations decreased more during low-flow conditions (3 ml/min) when hearts were perfused with hexanoate compared with glucose. Thus hexanoate decreases myocardial efficiency compared with glucose in large part by increasing non-work related oxygen demands. This inefficiency impacts adversely on contractile strength and high-energy phosphate concentrations at low coronary flows. PMID- 1887922 TI - Volumetric response of right ventricle during progressive supine exercise in men. AB - Right ventricular (RV) adaptation to supine exercise has been studied in 10 young male volunteers by 81mKr electrocardiogram (ECG)-gated radionuclide ventriculography. During progressive supine exercise, the ejection fraction gradually increased from a mean value of 46% at rest up to 60% at a maximal exercise level. End-diastolic volume however remained unchanged at a low exercise level and even slightly decreased at a higher exercise level. Little or no change in end-diastolic volume and an increase in ejection fraction produced a significant decrease in end-systolic volume and a net increase in stroke volume. These results indicate that the Frank-Starling mechanism does not contribute to the increase in right ventricular stroke volume during progressive supine exercise, but the increase in right ventricular stroke volume rather seems related to an increased contractility, presumably mediated by an increased sympathetic activity. PMID- 1887923 TI - Effect of H+ on ATP-regulated K+ channels in feline ventricular myocytes. AB - Using patch-clamp techniques, we examined the effects of pH on properties of ATP regulated K+ channels in single myocytes isolated from cat left ventricles. ATP K+ channels of inside-out patches were bilaterally exposed to 140 mM K+ solutions (22 degrees C). In the absence of ATP and Mg2+, the channels had a linear current voltage relationship during hyperpolarizing pulses (20-100 mV negative to the reversal potential) at both intracellular pH (pHi) 7.4 and 6.5, but the slope conductance was 66 +/- 2 pS at pHi 7.4 and 46 +/- 2 pS at pHi 6.5. Lowering pHi from 7.4 to 6.5 increased the mean open time (from 15.9 +/- 4.6 to 35.9 +/- 7.9 ms, P less than 0.01) but decreased the open-state probability measured at 50 mV positive to the reversal potential (from 0.35 +/- 0.04 to 0.16 +/- 0.04, P less than 0.01). However, in the presence of both 0.2 mM ATP and 1 mM MgCl2, lowering pHi from 7.4 to 6.5 increased the mean open time (from 5.0 +/- 2.6 to 17.9 +/- 5.9 ms, P less than 0.01) and the open-state probability (from 0.025 +/- 0.010 to 0.098 +/- 0.024, P less than 0.01). These data indicate that increases in intracellular H+ concentration modulate cardiac ATP-K+ channel properties. Ischemia-associated decreases in pHi may enhance the opening of cardiac ATP regulated K+ channels and resultant action potential shortening. PMID- 1887924 TI - Effects of coronary occlusion duration on reactive hyperemia in conscious dogs and ponies. AB - Coronary reactive hyperemia duration (RHD) and coronary blood flow debt repayment (BFDR) were compared in conscious dogs and ponies instrumented with coronary artery Doppler flow probes and pneumatic occluders. Additional ponies were instrumented with pacing electrodes. With the use of a Latin square design, eight animals of each species were subjected to a randomized series of nine coronary occlusions ranging from 5 s to 2 min in duration. In both species, postocclusion blood flow velocity rose rapidly and plateaued at similar peak levels relative to control, but in ponies this plateau lasted significantly longer. The interspecies difference in plateau duration increased as a function of coronary occlusion duration (COD). RHD ranged from 19.5 +/- 5.9 to 139.7 +/- 5.9 s in dogs and from 26.6 +/- 9.0 to 395.0 +/- 9.0 s in ponies. The slope of the RHD vs. COD curve was steeper in ponies. BFDR was similar in dogs and ponies at the shortest COD (418.1 +/- 26 vs. 451.4 +/- 58%) but declined in dogs as a function of COD to 232.3 +/- 26%. In ponies, BFDR increased as a function of COD to a maximum of 945.4 +/- 58% with a 60-s occlusion and then declined to 614.3 +/- 58%. RHD was not significantly altered in ponies when heart rate was changed to match that in dogs. Although the underlying basis for these interspecies differences in RHD and BFDR was not determined, the differences were considered to be too large to be explained by animal model differences in coronary conductance, collateral blood flow, or myocardial oxygen consumption.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1887925 TI - Decreased flow reserve in "stunned" myocardium after a 10-min coronary occlusion. AB - The effect of brief reversible ischemia on coronary vascular function remains controversial. Studies using a 15-min coronary occlusion have reported an impairment of vasodilator reserve, whereas studies using shorter occlusions have not. To elucidate the relation between postischemic vascular abnormalities and duration of ischemic insult, we evaluated coronary reserve after a 10-min coronary occlusion in the same model previously used for a 15-min occlusion. Open chest dogs (n = 12) underwent a 10-min left anterior descending coronary artery occlusion followed by reflow. Four hours after reperfusion, coronary resistance was higher in the postischemic "stunned" myocardium than in the nonischemic myocardium, both at rest and during adenosine-induced maximal vasodilation; in addition, all indexes of reactive hyperemia after a 40-s coronary occlusion were significantly lower than at baseline. There was no appreciable correlation between systolic wall thickening in the stunned myocardium and 1) the resting myocardial perfusion, 2) the hyperemia attained during adenosine, and 3) the hyperemic response to a 40-s coronary occlusion. The loss of coronary reserve was less than that previously observed after a 15-min occlusion, suggesting that the magnitude of the postischemic vascular abnormalities increases with the duration of the ischemic insult. In control dogs (n = 8), there was no change in coronary reserve. We conclude that a brief ischemic insult lasting only 10 min is sufficient to cause a prolonged increase in resting vascular resistance and a prolonged impairment in vasodilator responsiveness, both of which persist for at least 4 h, indicating the presence of a postischemic microvascular dysfunction. The severity of these vascular derangements is not related to the severity of the contractile depression, suggesting that they may represent a relatively independent phenomenon. The differences among previous studies may be due, in part, to the fact that the abnormalities observed after a 10-min occlusion are relatively subtle. PMID- 1887926 TI - Influence of systolic pressure profile on rate of left ventricular pressure fall. AB - We examined the influence of the systolic left ventricular pressure (LVP) waveform on the rate of isovolumetric LVP fall, as assessed by the time constant tau. Seven open-chest dogs were instrumented with a micromanometer in the left ventricle, with segment length gauges in the anterior and posterior midwall of the left ventricle, and with a balloon-tipped catheter in the proximal aorta. The intra-aortic balloon was inflated before the onset of ejection (early) or during midejection (late) to produce timed and graded increases in peak LVP of 2-20 mmHg. The rate of LVP fall slowed significantly more with late than with early increases in LVP (tau increased 1.5 +/- 0.5 vs. 0.5 +/- 0.3%/mmHg increase in peak LVP, respectively, P less than 0.001). For a similar increase in peak LVP, there was a progressively greater increase in tau when the timing of balloon inflation was progressively delayed from early to late ejection (in 10-ms increments). The differential effect of early vs. late pressure increases on tau was not related to regional differences in segment length behavior nor to an increase in regional nonuniformity between anterior and posterior sites. We conclude that under the experimental conditions of an intact, ejecting left ventricle, the systolic pressure profile is an important determinant of the rate of pressure fall. The rate of LVP fall slows in direct proportion to the magnitude of increase in systolic pressure. The sensitivity to systolic load increases progressively throughout the ejection period, so that the rate of LVP fall slows significantly more with late than with early pressure increases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1887927 TI - Hemodynamic effects of posterior hypothalamic injection of neuropeptide Y in awake rats. AB - Unilateral microinjection of neuropeptide Y (NPY) into the posterior hypothalamic nucleus was previously found to evoke a sympathoexcitatory-mediated increase in mean arterial pressure (MAP) in urethan-anesthetized rats. In this study, the effect of unilateral injection of NPY into the posterior hypothalamic nucleus on the cardiovascular system of conscious, freely moving rats was determined. Microinjection of NPY (0.2-2.4 nmol) or the cholinergic agonist carbachol (0.5 5.5 nmol) resulted in concentration-dependent increases in MAP. Pretreatment of animals with 7.5 mg/kg iv of the ganglionic blocker pentolinium resulted in a blockade of the increase in MAP evoked by microinjection of NPY (2.4 nmol) or carbachol (3.3 nmol). Despite their similarity of effects on MAP, NPY and carbachol evoked different changes in heart rate. NPY increased heart rate, whereas carbachol evoked a biphasic change in heart rate that consisted of an initial increase followed by a decrease. In addition, carbachol caused increases in both hindquarter and mesenteric vascular resistances, whereas NPY caused a short-lasting increase in mesenteric resistance and a tendency toward an increase in hindquarter resistance. Both NPY and carbachol increased total peripheral resistance while NPY decreased stroke volume. Cardiac output was not significantly affected by either NPY or carbachol, although NPY had a tendency to decrease cardiac output. These results suggest that microinjection of NPY or carbachol into the posterior hypothalamic nucleus of conscious rats evokes an increase in MAP primarily as a result of sympathoexcitation and that NPY and carbachol selectively affect autonomic nervous system control of the cardiovascular system. PMID- 1887928 TI - Peripheral circulatory control of cardiac output in diabetic rats. AB - Diabetes is believed to be associated with impaired systolic and diastolic function of the heart; however, some investigators have found that diabetic rats have increased cardiac output. We investigated changes in the peripheral circulation that could account for an increased cardiac output in diabetic rats (n = 30), 4 wk after a single tail vein injection of streptozotocin (60 mg/kg), and age-matched control rats (n = 31). Compared with controls, diabetic rats exhibited decreased (P less than 0.05) mean arterial pressure, characteristic aortic impedence, and total peripheral resistance; however, cardiac index and stroke volume index were increased. Aortic compliance, mean circulatory filling pressure, central venous pressure, pressure gradient for venous return, and venous compliance were unchanged in the diabetic rats compared with control. Baseline left ventricular end-diastolic pressure and end-diastolic volume were increased in the diabetic rats. Following a volume load of 30 ml/kg, cardiac index and stroke volume index increased less in the diabetic than in the control rats (35 vs. 102% and 69 vs. 105%, respectively). Thus, even with impaired systolic function, cardiac output is increased or maintained in diabetic rats because of the combination of decreased afterload and maintenance of preload. PMID- 1887929 TI - Enhanced synthesis of epoxyeicosatrienoic acids by cholesterol-fed rabbit aorta. AB - Arachidonic acid metabolism via cyclooxygenase, lipoxygenase, and cytochrome P 450 epoxygenase was investigated in thoracic aortic tissue obtained from rabbits fed either standard rabbit chow or chow containing 2% cholesterol. Aortic strips were incubated with [14C]arachidonic acid and A23187. Metabolites from extracted media were resolved by high-pressure liquid chromatography (HPLC). Normal and cholesterol-fed rabbit aortas synthesized prostaglandins (PGs) and hydroxyeicosatetraenoic acids (HETEs). The major cyclooxygenase products were 6 keto-PGF1 alpha and PGE2. Basal aortic 6-keto-PGF1 alpha production was slightly reduced in cholesterol-fed compared with normal rabbits. 12(S)- and 15(S)-HETE were the major aortic lipoxygenase products from both normal and cholesterol-fed rabbits. The structures were confirmed by gas chromatography-mass spectrometry (GC-MS). Only cholesterol-fed rabbit aortas metabolized arachidonic acid via cytochrome P-450 epoxygenase to the epoxyeicosatrienoic acids (EETs). 14,15-, 11,12-, 8,9-, and 5,6-EET were identified based on comigration on HPLC with known 14C-labeled standards and typical mass spectra. Incubation of normal aorta with 14,15-EET decreased the basal synthesis of 6-keto-PGF1 alpha. The other EETs were without effect. The four EET regioisomers relaxed the norepinephrine precontracted normal and cholesterol-fed rabbit aorta. The relaxation response to 14,15-EET was greater in aortas from cholesterol-fed rabbits. These studies demonstrate that hypercholesterolemia, before the development of atherosclerosis, alters arachidonic acid metabolism via both the cyclooxygenase and epoxygenase pathways. PMID- 1887930 TI - Effects of paraventricular nucleus lesions on chronic renal hypertension. AB - The contribution of the paraventricular nucleus region of the hypothalamus (PVN) to the maintenance of one-kidney, figure-8 renal wrap hypertension was determined in this study. Electrolytic ablation of the PVN was performed 4 wk after the production of hypertension or sham operation. Ablation of the PVN region significantly reduced mean arterial pressure (MAP) from 150 +/- 9 to 110 +/- 3 mmHg in the hypertensive rats. In the sham-hypertensive group, the lesion decreased MAP from 118 +/- 2 to 99 +/- 4 mmHg. In both groups of animals MAP from 118 +/- 2 to 99 +/- 4 mmHg. In both groups of animals MAP returned to prelesion values by day 7 postlesion. When ganglionic blockade was performed on day 7 postlesion, the fall in MAP was greater in hypertensive rats (-44 +/- 5 mmHg) than in normotensive rats (-26 +/- 3 mmHg). In a separate group of rats studied 3 days after PVN ablation, ganglionic blockade produced similar decreases in MAP in the wrapped and sham-operated animals. These studies suggest that the PVN contributes to the increased functional sympathetic nervous system associated with one-kidney, figure-8 renal hypertension. Although ablation of the PVN region decreases MAP, neural mechanisms compensate to return MAP to hypertensive levels. PMID- 1887931 TI - Role of H+ and alpha 2-receptors in escape from sympathetic vasoconstriction. AB - In a previous study, we noted that mesenteric venous pH falls during the reductions in intestinal blood flow caused by sympathetic stimulation and that alpha 2-receptor antagonists enhanced autoregulatory escape (the partial recovery that blood flow undergoes despite sustained sympathetic stimulation). In addition, other studies indicated that increased [H+] selectively inhibits the responsiveness of postjunctional alpha 2-receptors to norepinephrine (NE). Therefore, we investigated the role of H+ in escape by 1) measuring the rate of unbuffered H+ release during sympathetic stimulation in isolated loops of canine small bowel, 2) infusing acidic buffer intra-arterially and determining the effects of acidosis on sympathetic vasoconstriction and escape, 3) ascertaining the effects of acidosis on the release rate of endogenous NE during sympathetic stimulation, and 4) determining whether acidosis exerts effects in vivo on post junctional responses to the selective alpha 1- and alpha 2-agonists, phenylephrine and clonidine, respectively. Our findings were that 1) the rate at which the gut released H+ into blood increased during sympathetic stimulation, 2) infusing acidic buffer to lower venous pH from 7.3 to 7.1 attenuated the initial vasoconstrictor response after 30 s of stimulation, 3) acidosis caused blood flow to return further toward control despite continued stimulation and thus enhanced escape, 4) acidosis did not impair NE release at either 30 s or 6 min of stimulation, and 5) acidosis inhibited the intestinal vasoconstrictor effects of selective alpha 2- but not alpha 1-agonists. The results support the hypothesis that escape from sympathetic vasoconstriction occurs, in part, because increased [H+] inhibits alpha 2-mediated postjunctional responses to neuronally released NE. PMID- 1887932 TI - Influence of histaminergic receptors on denervated canine gracilis muscle vascular tone during endotoxemia. AB - The purpose of this study was to determine if endogenously released histamine and its non-neural interaction with the H1- and H2-histaminergic receptors in the peripheral vasculature can account for the decompensatory loss of peripheral vascular tone associated with the hypotension occurring during endotoxemia. A denervated in situ constant flow double canine gracilis muscle preparation that permitted one muscle to serve as a control (GMc) for the contralateral experimental muscle (GMe) was used. Endotoxemia was induced by intravenous infusion of 2 mg.kg-1.30 min-1 endotoxin. The specific H1 and H2 antagonists diphen-hydramine and cimetidine were infused either together or separately in both high and low dosages into the GMe. Blockades were validated by intra arterial injection of histamine or the specific agonists betahistine for H1 and dimaprit for H2 receptors. The results suggest that the high-dose diphenhydramine produced a nonspecific dilation not seen with the lower dose. Because both the blocked and unblocked vascular beds exhibited the same degree of vasodilation after endotoxin, these studies do not support the hypothesis that endogenously released histamine is responsible for the loss of vascular tone. These studies do verify, however, that a nonneurally mediated loss of skeletal muscle vascular tone is an important factor to consider in the overall cardiovascular hypotension occurring during endotoxin shock. PMID- 1887933 TI - Metabolic and functional consequences of blunted myocardial reactive hyperemia. AB - This study determined whether the rapidity of myocardial metabolic and contractile recovery after brief coronary occlusion depends upon the intensity of reactive hyperemia. We also tested the hypothesis that coronary flow rate modulates contractility after brief myocardial ischemia, independent of changes in phosphorus metabolites. Eight open-chest pigs were studied with phosphorus-31 nuclear magnetic resonance (NMR) spectroscopy with 14 s time resolution. After a 29-s anterior descending coronary occlusion, peak Doppler coronary flow velocity was alternately unrestricted (normal hyperemia, 443 +/- 40% of control) or limited to 159 +/- 9% of control. During 29 s coronary occlusion, phosphocreatine to-inorganic phosphate ratio (PCr/Pi) and systolic segment shortening in the ischemic region fell to 28 +/- 4 and 7 +/- 7% of control, respectively. With normal hyperemia, PCr/Pi and segment shortening recovered within 29 s. With blunted hyperemia, recovery of both parameters was delayed an additional 29-43 s, associated with reduced subendocardial blood flow (measured with radioactive microspheres) and persistent intracellular acidosis. However, the relationship between segment shortening and PCr/Pi was unaffected by the intensity of reactive hyperemia. Thus blunted reactive hyperemia significantly delays metabolic and contractile recovery from brief ischemia, probably via transient maldistribution of transmural perfusion. However, coronary blood flow rate does not independently modulate contractility after brief reversible ischemia. PMID- 1887934 TI - Interstitial adenosine concentration during norepinephrine infusion in isolated guinea pig hearts. AB - This study determined the effect of norepinephrine (NE) on cardiac interstitial fluid adenosine concentration [( ADO]isf). Isolated guinea pig hearts were perfused with a Krebs-Henseleit buffer solution. Radiolabeled albumin, sucrose, and adenosine were injected under control conditions and after 3 and 20 min of NE infusion to obtain multiple indicator dilution curves that were used to determine capillary transport parameters for adenosine. These parameters together with venous adenosine concentrations were used in a mathematical model to a calculate [ADO]isf. Capillary transport parameters were not changed significantly by NE infusion. Because of uncertainty regarding two model parameters, two sets of [ADO]isf values were calculated. One set used best-fit values obtained from indicator dilution curves, and a second set used parameters chosen to provide the highest [ADO]isf values consistent with indicator dilution curves. Venous adenosine concentrations were 1.9 +/- 0.4 nM under control conditions and 243 +/- 110 and 45 +/- 25 nM after 3 and 20 min of NE infusion, respectively. Calculated [ADO]isf was 2.6-9.4, 591-1,288, and 166-324 nM, respectively, under these same conditions. We conclude that NE infusion greatly increases [ADO]isf, and adenosine is responsible for most of the vasodilation at 3 min. The subsequent fall in venous concentration is due to a fall in [ADO]isf rather than to decreased capillary permeability. Vascular resistance remained low while [ADO]isf fell, which suggests that additional vasodilators are important during maintained NE infusion. PMID- 1887935 TI - Heart rate reduction improves myocardial ischemia in swine: role of interventricular blood flow redistribution. AB - Regional myocardial blood flow (MBF) distribution and function upon slowing the heart rate (HR) during ischemia were studied in anesthetized swine, a species without coronary collaterals. Perfusion of the left anterior descending artery by a pump allowed controlled production of regional ischemia. Slowing tachycardia by electrical pacing (127 to 87 beats/min) caused marked improvement of regional dysfunction [% wall thickening (WTh) from 9 to 27%] and increased subendocardial MBF [from 0.31 to 0.55 ml.min-1.g-1 (P less than 0.001)] without change of subepicardial MBF. Total left ventricular (LV) MBF increased, whereas right ventricular (RV) MBF fell by 18% (P less than 0.02). The mechanism of MBF changes during slowed HR was assessed by surgically excluding the RV and comparing findings with previous experiments with RV intact when HR was slowed from 96 to 60 beats/min. A similar improvement of regional LV function occurred (8% vs. 30% WTh) with the RV excluded, but without a change in total flow to the LV bed, whereas subendocardial MBF increased and subepicardial MBF fell, indicating transmural redistribution only. These findings show that the RV vascular bed can contribute to LV perfusion in swine during ischemia, and they document the potential for "reverse RV steal" during slowed heart rate in this setting. PMID- 1887936 TI - Transmural distribution of three-dimensional strain in the isolated arrested canine left ventricle. AB - Three-dimensional myocardial strains in seven isolated, potassium-arrested dog hearts were measured by biplane radiography of 3 transmural columns of 4-6 radiopaque beads implanted in the midanterior left ventricular free wall. Transmural distributions of strain during inflation of a left ventricular balloon to 20-30 mmHg were computed with respect to the zero pressure state. Magnitudes of the 3 principal strains increased in proportion to ventricular volume (0.0088, 0.0037, and -0.0059 ml-1). At a left ventricular pressure of 8 +/- 4 mmHg, mean circumferential (E11) and longitudinal strains (E22) were similar, increasing from epicardium (0.058 +/- 0.055 and 0.036 +/- 0.024) to subendocardium (0.139 +/ 0.102 and 0.120 +/- 0.084) as did the transmural (wall thinning) strain E33 ( 0.053 +/- 0.071 to -0.128 +/- 0.083). Negative in-plane shear E12 was small ( 0.008 to -0.052), consistent with a left-handed torsion of the left ventricular wall. Mean transverse shear strains E13 and E23 were small (-0.029 to 0.007) but showed considerable variability between hearts. Fiber strain had no significant transmural variation (P = 0.57). The principal axis of greatest strain was close to the fiber orientation on the epicardium (-15 degrees) but closer to the cross fiber direction near the endocardium (-40 degrees). Therefore, the end-diastolic fiber lengths are maximized on the epicardium and minimized on the endocardium. PMID- 1887937 TI - Optimal design of experiments to estimate LDL transport parameters in arterial wall. AB - To quantify transport processes in atherosclerosis, the arterial wall is often exposed to labeled lipoproteins. In vivo experiments are desirable for estimation of transport parameters, but they are technically difficult. A dynamic mass transfer model has been developed to describe experimental transmural profiles of lipoprotein accumulation as a function of luminal permeability, diffusion, convection, and degradation. To avoid extraneous experiments and to assure successful parameter estimation, an optimal design of experiments is needed. For our purposes a design was considered optimal when it maximized the sensitivity of the model output to changes in parameter values as indicated by the determinant of the Hessian matrix of the objective function. A comparison was made between two designs: dual-time designs prescribing unequal circulation times for two distinguishable injections of labeled low-density lipoprotein (LDL) and dual species designs requiring simultaneous circulation of LDL and tyramine-cellobiose modified LDL. Circulation time was optimized for both designs. Although both were heavily dependent on the circulation times, dual-time designs required better preliminary knowledge of parameter values. Because labeled degradation products of the modified tracer become anchored in the arterial tissue, information about the degradation process is retained in the dual-species study. For this reason, dual-species designs were generally superior to dual-time designs. PMID- 1887939 TI - Measurement of blood flow in rat eyes by hydrogen clearance. AB - Intraocular measurements of blood flow have been made in the rat eye using hydrogen-clearance polarography. Hydrogen was delivered by a bolus injection of hydrogen-saturated saline via a cannula in the lingual artery of the anesthetized rat. An intraocularly placed hydrogen-sensitive microelectrode monitored the arrival and clearance of hydrogen preretinally adjacent to retinal arteries, veins, and intervascular areas. The effect of stepwise penetration through the retina and into the choroid was also determined, and a map of hydrogen distribution in the retina during hydrogen delivery and clearance was produced. Intraocular measurements, which have the advantage that the electrode location can be clearly visualized, together with computer control of the bolus injection and data collection, have allowed highly repeatable measurements of local blood flow to be made. The mean blood flow in retinal tissue was 373 +/- 51 ml.min 1.100 g-1 (values are means +/- SD, n = 32). The correlation between the nature of the hydrogen clearance curve and the location of the electrode helps explain data from other studies in which the position of the electrode with respect to the vasculature was unknown. PMID- 1887938 TI - Calcium measurement in isolated arterioles during myogenic and agonist stimulation. AB - Vascular smooth muscle calcium was measured during agonist treatment or pressure induced stimulation of the myogenic response in isolated first-order skeletal muscle arterioles. Arterioles (40-180 microns) with spontaneous tone were isolated from rat cremaster muscle and cannulated. Arterioles were loaded with the calcium-sensitive dye fura-2 and excited at 340 and 380 nm. Images of vessel fluorescence were formed with a fluorescence microscope and digitized using an image processor coupled to a low light level camera. The fluorescent images allowed individual vascular smooth muscle cells to be seen within the arteriolar wall. Fluorescent intensity of the vessel wall, expressed as the ratio of fluorescence at 340 nm/380 nm, was used to estimate changes in vessel wall calcium. Topical application of norepinephrine (10 microM) to the arterioles caused a rapid and sustained constriction of the arterioles (64% of basal diam). The calcium response was biphasic consisting of a transient spike to 271% of basal followed by a decrease to a new steady state at 143% of basal. In comparison, steady-state indolactam (1 microM) produced a similar degree of constriction without an increase in calcium. Adenosine significantly dilated (35%) the arterioles and produced a decrease (24%) in vessel wall calcium. To investigate the myogenic response, intravascular pressure was step increased from 90 to 130 cmH2O. Increasing intravascular pressure caused an initial increase in vessel diameter of approximately 5% followed by active constriction that returned diameter to basal diameter. In association with this diameter change, estimated vessel wall calcium increased rapidly 8 +/- 2% and then continued to increase more slowly and remained elevated at 10-15% above basal levels. This study demonstrates the successful application of calcium-imaging technology in isolated arterioles for study of the role of calcium in arteriolar function. Results indicate that the calcium-contraction relationship differs for different agonists and are further consistent with a role for pressure-induced increases in vascular smooth muscle calcium during the myogenic response. PMID- 1887940 TI - Similar pressure pulse propagation and reflection characteristics in aortas of mammals. AB - Similar pressure and flow waveforms recorded in mammalian aortas suggest that pulse transmission characteristics may also be similar. We examined the validity of this hypothesis, utilizing allometric equations of pertinent hemodynamic parameters and a model of the arterial system. Results show that both the reflection coefficient and the propagation constant times the aortic length are essentially invariant across the mammalian species investigated. Resolved forward and reflected propagating waves are also similar. These findings suggest that the arterial system in these mammals indeed functions in a similar manner. PMID- 1887941 TI - Thermoregulation, growth, and reproduction in Alaskan collared lemmings: role of short day and cold. AB - To assess factors controlling seasonal thermoregulatory and reproductive changes, collared lemmings (Dicrostonyx groenlandicus) were exposed for 16 wk to long day (LD, 22 h light: 2 h dark) and warm (15 +/- 3 degrees C), LD and cold (1 +/- 0.5 degrees C), short day (SD, 4 h light: 20 h dark) and warm, SD and cold or acclimatized to outdoor winter conditions (OUT). Hair length and color, body mass, and food intake were monitored weekly. Resting metabolic rates (RMR) and nonshivering thermogenesis (NST) were estimated several times by measuring oxygen consumption before and after norepinephrine injections. Body composition and reproductive condition were determined at the end of the experiment. SD and OUT groups had a 15.8% lower (P less than 0.01) RMR at 7 degrees C than the LD groups. Lower thermal conductance in SD and OUT animals appears due to molt to white winter pelage, which occurred by week 3 in SD but not in LD groups. Neither SD, cold, nor OUT altered NST or reproductive morphology. SD-exposed lemmings showed 19.2% greater growth than those in LD, resulting primarily from a 29.2 and 15.0% increase in lean and ash components, respectively. Cold exposure increased food intake by 34.7%. Results suggest that the pineal gland, which mediates SD effects, may influence molt and growth but not NST or reproductive morphology. PMID- 1887942 TI - Effects of pylorectomy on cholecystokinin-induced inhibition of liquid gastric emptying. AB - The present study was designed to investigate a role for the pyloric sphincter and its population of cholecystokinin (CCK) receptors localized to the circular muscle layer in the inhibition of gastric emptying produced by exogenously administered CCK in rats. We examined the ability of two doses of CCK to inhibit the gastric emptying of 10-ml saline (0.9% NaCl) and glucose (0.125 g/ml) test meals in rats equipped with chronic gastric fistulas before and after surgical removal of the region of the pylorus containing CCK receptors. Preoperatively, CCK (2 and 8 micrograms/kg) inhibited gastric emptying of both saline and glucose. Pylorectomy did not significantly alter the baseline saline and glucose emptying and did not alter the ability of CCK to inhibit the emptying of the saline test meals. In contrast, pylorectomy eliminated the ability of CCK to inhibit glucose emptying. These results demonstrate that the inhibition of gastric emptying by CCK may involve multiple mechanisms depending on the character of the gastrointestinal contents. PMID- 1887943 TI - Bradykinin-induced prostaglandin synthesis is enhanced in keratinocytes and fibroblasts by UV injury. AB - Ultraviolet (UV) light exposure substantially modifies the host immune response, in part through the synthesis of prostaglandins. Work examining the mechanisms by which UV irradiation stimulates prostaglandin synthesis has focused on mediators that increase in quantity after irradiation. The present work demonstrates that UV irradiation injury increases the sensitivity and maximum response of keratinocytes to bradykinin, suggesting that agonist quantities need not increase in injured tissue to contribute to inflammation. The ability of UV injury to increase bradykinin-stimulated prostaglandin synthesis is not limited to keratinocytes, as irradiation produced a similar response in fibroblasts. Receptor binding studies demonstrate that the enhanced response of irradiated cells is not due to increased bradykinin binding. These data suggest that UV irradiation may cause cells to increase their response to an array of inflammatory mediators present in injured tissue, whether or not the quantity of the mediator increases. PMID- 1887944 TI - Normal food intake and growth in hyperprolactinemic rats. AB - Normal lactation, a state of chronic hyperprolactinemia, is often accompanied by increased food intake. Two recent reports suggested that, in rats, prolactin (PRL) administration or chronic endogenous PRL excess led to increased food intake and growth. Similar methods of achieving augmented circulating levels of PRL in rats have been employed in our laboratory. Rats with extra anterior pituitary (AP) grafts under the kidney capsule have chronically elevated circulating PRL levels. However, in several experiments, weight gain, food intake, and fecal weight were the same in AP-grafted rats and in control muscle grafted rats. In addition, the AP-grafted rat model was modified to demonstrate that PRL-induced increases in adrenal glucocorticoids and decreases in estrogens did not provoke alterations in eating behavior. Injection of homologous PRL for 8 days did not increase weight gain in normal or hypophysectomized rats. These data suggest that neither the chronic PRL excess caused by AP grafts nor the acute PRL excess caused by rat PRL injections increases food intake or weight gain. PMID- 1887945 TI - Development of mammalian endothermic metabolism: quantitative changes in tissue mitochondria. AB - The development of energy metabolism of mammalian tissues was assessed in the tammar wallaby Macropus eugenii by the measurement of mitochondrial parameters in the liver, heart, kidney, and brain. Tissues taken from wallabies (n = 27) ranging from 10-day-old pouch young (weighing approximately 4 g) to adults (averaging 6.2 kg) were weighed and fixed, and mitochondrial volume and mitochondrial membrane surface area (MMSA) were determined by quantitative electron microscopy techniques. Developmental changes in these parameters were analyzed chronologically and allometrically. Relative growth rates of all four tissues decreased during development. Liver and heart showed constant allometric growth throughout development, whereas kidney and brain showed biphasic allometric growth. Tissue metabolic intensity assessed by MMSA (m2/cm3 tissue) was constant in liver, showed a threefold increase in brain during pouch life, showed a fourfold increase in the heart between 100 and 200 days of age, and showed a twofold increase in the kidney at the end of pouch life. In all tissues, adult levels of tissue metabolic capacity were present at pouch exit. In all four tissues, total MMSAs were at "reptilian" levels at birth and gradually increased to "mammalian" levels. Each tissue exhibited a different developmental timetable. When the total MMSAs for all four tissues were summed there was a similar pattern of allometric development between summed MMSA and whole animal metabolic rate. PMID- 1887947 TI - Endothelin action on cerebral circulation in unanesthetized goats. AB - The effects of endothelin 1 on the internal maxillary artery blood flow, measured as an index of cerebral blood flow, were examined in six unanesthetized goats under control conditions, hypercapnia induced by inhalation of 10% CO2 in air, hypertension by intravenous infusion of norepinephrine, and hypotension by intravenous injection of diazoxide. Under control, administration of endothelin (0.01-0.3 nmol) into the internal maxillary artery produced dose-dependent sustained decreases in cerebral blood flow and increases in cerebrovascular resistance; higher doses (0.1 and 0.3 nmol) also caused hypertension and bradycardia. During hypercapnia or hypertension, endothelin did not significantly affect cerebral blood flow, and only higher doses (0.1 and/or 0.3 nmol) increased cerebrovascular resistance, but this was lower than under control. However, under hypotension endothelin evoked a higher reduction in cerebral blood flow and increment in cerebrovascular resistance, and systemic effects were also more marked than under control. Therefore endothelin is a potent cerebral vasoconstrictor, and this effect is very attenuated during hypercapnia and hypertension but is increased under hypotension. PMID- 1887946 TI - Patterns of duodenal osmolality in young pigs fed solid food. AB - Duodenal hypertonicity can induce satiety, but whether duodenal osmolality varies during eating enough to influence meal size is not clear. To find out more about this, duodenal samples were taken via implanted catheters from 10 young pigs under three feeding conditions. 1) The pigs were fasted 4-5 h and then given a meal with drinking water available. Duodenal osmolality rose from a premeal level of 297 mosmol/kgH2O to a peak of 430 mosmol/kgH2O at 35 min after the meal began and then returned to the premeal level after 2.2 h. 2) When pigs were similarly fasted and then given a meal, but with no drinking water available during and after the meal, osmolality rose to 418 mosmol/kgH2O after 35 min and only returned to premeal levels after 4.2 h. 3) Finally, when pigs were allowed to eat and drink spontaneously, osmolality rose from a mean of 281 to only 308 mosmol/kgH2O after meals, in part because of water drinking in association with meals and in part because the spontaneous meals were smaller. The results demonstrate that duodenal osmolality can rise significantly after meals but that hyperosmolality is moderated by water drinking. PMID- 1887948 TI - Pressure natriuresis and cortical and papillary blood flow in inbred Dahl rats. AB - The present study examined whether alterations in papillary blood flow, renal interstitial pressure (RIHP), and the pressure-natriuretic (PN) response are associated with the development of hypertension in inbred Dahl salt-sensitive (Dahl-S) rats. The PN responses were compared in 18- to 20-wk-old, Inactin anesthetized, inbred Dahl salt-sensitive (S/Jr) and salt-resistant (R/Jr) rats fed a low-(0.3%) and a high- (8.0%) sodium chloride diet. Cortical and papillary blood flows were measured using laser-Doppler flowmetry. Neural and hormonal influences on the kidney were controlled by renal denervation and by fixing plasma norepinephrine, vasopressin, corticosterone, and aldosterone levels by intravenous infusion. The slope of the PN relationship in S/Jr rats maintained on a low-salt diet was 62% lower than that observed in R/Jr rats; however, whole kidney, cortical, and papillary blood flows and RIHP were not significantly different at any perfusion pressure studied. Glomerular filtration rate (GFR) was 25% lower in S/Jr rats than in R/Jr animals maintained on a low-salt diet. The slopes of the PN responses were similar in S/Jr and R/Jr rats exposed to a high salt diet, but the entire relationship was shifted toward higher pressures by 20 mmHg in the S/Jr rats. Control cortical and papillary blood flows measured at control mean arterial pressures of 126 +/- 3 and 167 +/- 5 mmHg in R/Jr and S/Jr rats, respectively, were not significantly different. However, cortical and papillary blood flows were 25% lower in the S/Jr than in the R/Jr rats exposed to a high-salt diet when compared at equivalent renal perfusion pressures.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1887949 TI - Selective effects of sodium and chloride depletion on salt appetite in rats. AB - Findings from hypertension research indicate that dietary sodium chloride (NaCl), Na+, and Cl- independently influence blood pressure, electrolyte metabolism, and hormone secretion. In this context, we examined the effects of NaCl, Na+, and Cl- depletion, respectively, on the development of saline preference (salt appetite) in rats. Male Wistar rats were given a normal diet (1% NaCl) for 15 days and tested for salt appetite using a two-bottle choice test, one bottle containing water and the other 0.3 M saline. The animals were then divided into three groups (n = 11/group): one group received low NaCl, another received a Na(+)-deficient, normal-Cl-diet (low Na+), and a third received a Cl(-)-deficient, normal-Na+ diet (low Cl-). Salt appetite was again tested after 19 days on these diets. Both NaCl and Na+ depletion stimulated saline intake (P less than 0.01), whereas salt appetite did not change in the low-Cl- group. Water intake was not influenced by the regimens. In addition, no alterations were noted for weight, systolic blood pressure, plasma Na+ concentration, or blood pH. Dietary Cl-depletion, however, significantly reduced plasma Cl- concentration (P less than 0.05), and reduced plasma potassium in relation to rats depleted in Na+ (P less than 0.05). Plasma renin activity and urinary aldosterone were elevated in low-NaCl and Na(+) depleted rats relative to the Cl(-)-depleted group (P less than 0.05). These results suggest that salt appetite is increased by dietary Na+ deficiency but not by Cl- deficiency. Salt appetite may be controlled by central or peripheral systems specifically sensitive to Na+ or by hormonal changes characteristic of Na+ depletion, such as the activation of renin and aldosterone observed in the low-NaCl and low-Na+ groups. PMID- 1887950 TI - Allometry of cooling, supercooling, and freezing in the freeze-tolerant turtle Chrysemys picta. AB - Although several vertebrates are freeze tolerant, little is known of the relationship between body size and the kinetics of cooling and freezing. We compared these responses for six hatchling and eight adult Chrysemys picta from an Ohio population. All turtles initially recovered from freezing, and all adults, but only two hatchlings (which experienced ice contents of approximately 35%), exhibited long-term survival. Rapid thawing may have compromised hatchling survival. Turtle water content was inversely related to body mass, but we found no significant correlation between the extent of supercooling and body size. Prefreezing and postfreezing cooling rates scaled with body mass to the -0.55 and -0.40 power, respectively, but the latter rate was more than two orders of magnitude slower. Theoretical (assuming 20% bound water) and calorimetric estimates of body ice agreed reasonably well. Ice contents were both body mass and time dependent. The absolute rate of ice formation scaled with body mass to the 0.4 power. Body size strongly influences the freezing response of ectotherms and deserves more attention. PMID- 1887951 TI - Hypothalamic lesions increase saline ingestion induced by injection of angiotensin II into AV3V in rats. AB - Water and 3% NaCl intake were increased by the injection of 4 ng angiotensin II (ANG II) into the anteroventral third ventricle (AV3V) region of rats. Pretreatment with two specific ANG II receptor antagonists, [octanoyl-Leu8]ANG II and [Leu8]ANG II, significantly reduced ANG II-induced water and saline intake. This inhibition lasted approximately 30 min, with partial recovery at 60 min. In rats with electrolytic lesion of the bilateral ventromedial nucleus of hypothalamus (VMH), the effect of ANG II on water intake was not different from that observed in sham rats, but saline ingestion increased. In summary, the present results show that the AV3V region is an important central structure for ANG II-induced saline ingestion. Lesion of the VMH increases the response to ANG II, showing an interaction between the AV3V region and the VMH in the regulation of salt ingestion. PMID- 1887952 TI - Differential feeding responses to bacterial lipopolysaccharide and muramyl dipeptide. AB - The present study was designed to test whether a tolerance to the hypophagic effects of bacterial lipopolysaccharide (LPS) and muramyl dipeptide (MDP) develops with repeated injections in rats and whether a relationship between the hypophagic effects of both compounds exists. Only the first of three subsequent intraperitoneal injection of LPS (100 micrograms/kg body wt each), given every 2nd day, led to a significant reduction of food intake. In contrast, MDP (1.6 mg/kg body wt) did not lose its hypophagic effect with four subsequent intraperitoneal injections. Furthermore, the LPS tolerance did not alter the hypophagic response to subsequently injected MDP. Likewise, MDP pretreatment did not alter the hypophagic response to LPS. Doses of MDP and LPS that were individually below the threshold for a reliable reduction of food intake (0.4 mg MDP/kg body wt + 25 micrograms LPS/kg body wt) reduced food intake synergistically when injected together. The hypophagia produced by combined injections of MDP plus LPS slowly diminished with repeated injections. The results indicate that separate but interacting mechanisms are involved in the feeding responses to MDP and LPS. The observed synergism between MDP and LPS suggests a synergistic role of bacterial muramyl peptides and LPS in the anorexia during bacterial infections. PMID- 1887953 TI - Effect of V2 antagonist on clearance of arginine vasopressin by isolated perfused rat kidneys. AB - Isolated rat kidneys were perfused with Krebs-Henseleit-bovine serum albumin solution at a mean pressure of 99 +/- 2.6 mmHg. After control periods, arginine vasopressin (AVP) was added to the perfusate at a final calculated concentration of 25 pg/ml (2.5 x 10(-11) M). Urine and perfusate samples were collected at 15 min intervals for the following 60 min to measure kidney function and the renal clearance of immunoreactive AVP (irAVP). At 15-30 min after the addition of AVP, total renal clearance of irAVP was 1,623 +/- 190 microliters.min-1.g kidney wt-1. Glomerular filtration accounted for 35 +/- 3.0% of the total clearance, and 65 +/ 10.3% was cleared by peritubular pathways. Of the filtered irAVP, 48 +/- 4.8% was recovered in the urine. To investigate the importance of V2 receptors in the metabolism of AVP, clearance measurements were made in the presence of the V2 antagonist [d(CH2)5,D-Ile2,Ile4,Arg8]AVP (5 x 10(-9) M). Total renal clearance of irAVP was reduced by 48% to 848 +/- 79 microliters.min-1.g-1. This reduction was entirely accounted for by the complete inhibition of peritubular clearance of irAVP. In the presence of the V2 antagonist, irAVP was cleared only by filtration. The proportion of filtered AVP recovered in the urine (53 +/- 8.7%) was not significantly altered by the presence of the V2 antagonist. We conclude that a major component of the renal clearance of AVP depends on receptor-mediated uptake of AVP in the kidney cells. PMID- 1887954 TI - Circadian characteristics of Djungarian hamsters: effects of photoperiodic pretreatment and artificial selection. AB - Bidirectional artificial selection for (High Line) and against (Low Line) photoresponsiveness altered the percent of photoresponsive hamsters within lines and affected circadian function of hamsters identical in photoresponsiveness. For example, free-running period was shorter in responsive relative to nonresponsive hamsters. Between-line differences for responders and nonresponders were also found: hamsters from the High Line had a shorter free-running period relative to Low Line hamsters. However, phase angle of entrainment to long and short days was not affected. In general, expression of circadian rhythmicity was extraordinarily inflexible in photononresponsive hamsters from both lines: 1) phase angle of entrainment to lights on was similar under short and long day; 2) activity duration was similar under long and short days, although some decompression occurred in constant dark; 3) aftereffects on the free-running period were absent; and 4) amplitude of the phase-response curve was small (+/- 1 h) and present only at circadian times 10-24. We propose that selection for or against photoresponsiveness may have affected the interaction of component oscillators underlying circadian rhythmicity. PMID- 1887955 TI - Role of vasopressin in acutely altered baroreflex sensitivity during hemorrhage in rats. AB - Experiments were performed to examine the potential role of circulating arginine vasopressin (AVP) on baroreflex sensitivity during hypotensive and nonhypotensive hemorrhage in the conscious rat. Animals were chronically instrumented for measurement of cardiac output, blood pressure, and heart rate (HR). Three potential stimuli for release of AVP were utilized: 1) rapid 20% arterial hemorrhage that resulted in hypotension, 2) nonhypovolemic hypotension induced by intravenous infusion of nitroprusside, and 3) nonhypotensive hemorrhage (rapid 10% arterial blood withdrawal). Hypotensive hemorrhage was associated with significant reductions in blood pressure, cardiac output, HR, and calculated total peripheral resistance, an increase in baroreflex (BRR) bradycardia in response to pressor infusions of phenylephrine, and a moderate elevation in circulating AVP. Prior intravenous administration of a specific V1 vasopressinergic antagonist augmented the hypotensive response to hemorrhage; however, neither V1- nor V2-blockade affected hemorrhage-induced augmentation of the BRR. Inducement of hypotension by infusion of nitroprusside did not alter subsequent BRR sensitivity. Finally, nonhypotensive hemorrhage was associated with an increase in resting HR and augmented BRR sensitivity. However, in contrast to hypotensive hemorrhage, either V1- or V2-antagonism attenuated the increase in BRR sensitivity seen with 10% hemorrhage. These data suggest that, although AVP may play a role in blood pressure maintenance via its direct vasoconstrictor actions during hypotensive hemorrhage, the observed augmentation of BRR sensitivity associated with severe blood loss is not attributable to a vasopressinergic mechanism activated by circulating AVP. However, blood-borne AVP may contribute to BRR sensitivity alterations in response to mild blood loss. PMID- 1887956 TI - Role of circulation in maintaining Na+ and K+ concentration in pelvic patch in Rana catesbeiana. AB - Skin samples from the pelvic, pectoral, and back areas of frogs were taken from control (C) animals and from dehydrated animals under three conditions: dehydrated and not exposed to a bathing medium (D), dehydrated live and ventral surface exposed to a bathing medium (DL), and dehydrated with heart stopped and ventral surface exposed to a bathing medium (DHS). The skin concentration of Na+ and K+ of the pelvic patch in the absence of circulation was significantly reduced [DHS 286 +/- 22 microM/mg dry wt (n = 6)] compared with control [C 392 +/ 21 microM/mg dry wt (n = 8)]. However, the pelvic skin concentration was maintained in a frog with an intact circulation [DL 381 +/- 26 microM/mg dry wt (n = 7)] even in the presence of a high pelvic water flow [684 +/- 105 cm3.cm-2.s 1.10(-7) (n = 13)]. The water uptake in the pectoral region [231 +/- 54 cm3.cm 2.s-1.10(-7) (n = 13)] was not high enough to predict a dilution, and none was found. The concentrations were 354 +/- 21 (n = 8), 359 +/- 22 (n = 7), 353 +/- 26 (n = 7), and 373 +/- 45 microM/mg dry wt (n = 6) for C, D, DL, and DHS, respectively. Examination of the Na+ and K+ concentrations separately in the pelvic skin shows that the lower salt content in DHS frogs is mainly due to a loss of Na+.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1887957 TI - Effects of intravenous infusions of angiotensin II on muscle sympathetic nerve activity in humans. AB - The effect of angiotensin II (ANG II) on the sympathetic outflow was examined in normal humans. The mean arterial pressure and muscle sympathetic nerve activity (MSNA) were measured before and during intravenous infusions of phenylephrine (0.5 and 1.0 micrograms.kg-1.min-1) or ANG II (5, 10, and 20 ng.kg-1.min-1) for 15 min at 30-min intervals. The baroreflex slope for the relationship between the increases in mean arterial pressure and the reductions in MSNA was significantly less acute during the infusions of ANG II than during the infusions of phenylephrine. When nitroprusside was infused simultaneously to maintain central venous pressure at the basal level, MSNA significantly increased during the infusions of ANG II (5 ng.kg-1.min-1 for 15 min) but not during the infusions of phenylephrine (1.0 micrograms.kg-1.min-1 for 15 min), with accompanying attenuation of the elevation in arterial pressure induced by these pressor agents. These findings suggest that ANG II stimulates the sympathetic outflow without mediating baroreceptor reflexes in humans. PMID- 1887958 TI - Gestational maturation of placental glucose transfer capacity in sheep. AB - The net transfer rate of glucose to the fetus from the placenta (Rf,up) increases approximately 10-fold over the second half of pregnancy. To examine the mechanism underlying this increase, we measured Rf,up at different glucose concentration gradients between maternal arterial (GA) and umbilical arterial (Ga) glucose and at three fetal ages: midgestation (76.0 +/- 0.6 days, n = 6), late gestation (131.5 +/- 2.1 days, n = 8), and an intermediate age (103.3 +/- 1.9 days, n = 4). The GA -- Ga gradient was varied by changing Ga below and above control values with fetal insulin and glucose infusions, respectively, while GA was kept constant at 70 +/- 2 mg/dl by a glucose clamp procedure. The slope of the line relating Rf,up to GA -- Ga increased from 0.15 to 1.01 dl/min in the 76- to 131.5 day period, while the intercept in the GA -- Ga axis remained approximately constant at 34 mg/dl. This indicates a fivefold increase in the ability of the placenta to supply glucose to the fetus at fixed values of maternal and fetal glucose concentration (placental glucose transfer capacity). Concomitant with this increase, there was a significant (P less than 0.001) decrease in control Ga from 26.7 +/- 1.3 to 20.3 +/- 0.3 mg/dl, leading to a significant increase in the GA -- Ga gradient and an 11-fold increase in control Rf,up (from 1.53 to 16.77 mg/min). We conclude that, in the second half of pregnancy, fetal glucose demand grows much more rapidly than placental glucose transfer capacity and requires a decrease in fetal glucose concentration to balance glucose supply and demand. PMID- 1887959 TI - Dynamics of behavioral thermoregulation in the rat. AB - Past studies have found that the laboratory rat placed in a temperature gradient prefers temperatures that are markedly below its lower critical ambient temperature (LCT), whereas other rodents (e.g., mouse, hamster, and guinea pig) generally select thermal environments associated with minimal metabolic expenditure. To further study the rat's thermoregulatory behavior, a temperature gradient was designed to monitor the selected ambient temperature (STa) and motor activity (MA) of food-deprived rats of the Long-Evans (LE), Fischer 344 (F344), and Sprague-Dawley (SD) strains over a 22-h period. All three rat strains selected relatively cool STas of 21-26 degrees C during the first 1-3 h in the temperature gradient. This was followed by a gradual increase in the STa that peaked at 4 (F344) to 6 h (SD and LE) after being placed in the gradient. The LE strain had a significantly lower STa during the initial period in the gradient. There were slight decreases in the STa during the nocturnal phase in the F344 and SD strains concomitant with marked increases in MA. These results indicate that the rat requires a relatively long adjustment period in a temperature gradient before it exhibits STas that are associated with minimal metabolic expenditure. Given adequate time for accommodation, behavioral thermoregulatory responses of the rat appear to be similar to those of other rodents. PMID- 1887960 TI - Contribution of renal medullary mitochondrial density to urinary concentrating ability in mammals. AB - In mammals, the length of the loops of Henle increases with increasing body size without a concomitant rise in urinary concentrating ability. Because mass specific metabolic rate falls with increasing body mass, this study sought to determine the extent to which this decline in metabolic rate could explain the low urinary concentrating ability of large mammals with long loops of Henle. Mitochondrial ultrastructural parameters were measured in the medullary thick ascending limbs (mTALs) of a series of nine mammalian genera ranging in body mass from 0.011 kg (bats) to approximately 400 kg (horses). The volume of mitochondria as a percent of mTAL cellular volume declined with increasing body mass (Mb 0.056). Inner mitochondrial membrane area per volume of mitochondrion also declined with increasing body mass (Mb-0.034), as did basolateral membrane area per unit mTAL cellular volume (Mb-0.075). Thus, not only do mitochondria occupy more volume of mTAL cells of smaller mammals, but those mitochondria are also more densely packed with cristae. Inner mitochondrial membrane area per unit volume of mTAL cell cytoplasm scaled as Mb-0.092. The decline in inner mitochondrial membrane area and basolateral membrane area per volume of mTAL cell may explain at least in part the relationship between body mass and renal concentrating ability in mammals of different sizes. PMID- 1887961 TI - Medial medullary contribution to tonic descending inhibition of visceral input. AB - In the present study, we sought to define the extent and source of tonic descending modulation of spinal neurons receiving visceral input from the afferent renal nerve (ARN). Spinal gray neurons responding to stimulation of the ARN in 64 chloralose-anesthetized rats were located primarily in laminae IV and V (70%), with fewer neurons located in laminae I and VII. ARN stimulation excited 76 and inhibited 8 neurons. Analysis of response latencies demonstrated that responses were due to activation of A delta- and/or C-fiber afferents. Reversible spinalization with cervical cold block (2-5 degrees C) affected activity in most neurons excited by ARN stimulation without affecting inhibited neurons. Cervical cold block increased the spontaneous activity of (disinhibited) the majority of neurons (54 of 76 neurons) and disfacilitated the spontaneous activity of 14 neurons. The evoked response to ARN stimulation was disinhibited by cold block in 51% and disfacilitated in 17% of the neurons, and there was a good correlation between neurons with disinhibited spontaneous activity and those with disinhibited evoked activity. Microinjections of muscimol (0.5-1 nmol) into the rostral medial medulla affected spontaneous and ARN-evoked activities similarly to cold block in 14 of 15 neurons, although the responses to muscimol were usually smaller in magnitude. We conclude that ARN input is modulated supraspinally and that the nucleus raphe magnus and adjacent neuropil contain neurons that contribute to tonic supraspinal inhibition of renal input in the rat. PMID- 1887962 TI - Measuring the lipid content of live animals using cyclopropane gas. AB - The cyclopropane technique was validated, and it accurately estimated the lipid mass of six pond turtles (Trachemys scripta). This technique provided more accurate estimates of lipid mass and lipid-free mass (by difference) than other nonfatal techniques. This technique was accurate despite the turtles' low lipid contents (0.71-3.5% of body mass), variable water contents (65-74% of body mass), and variable body temperatures (approximately 23-31 degrees C). A computer model of the cyclopropane technique revealed that an analytical error of 1% in variables measured (e.g., body water content and body temperature) may cause errors of less than 1-6% in lipid estimates. PMID- 1887963 TI - Microdialysis of cat pons reveals enhanced acetylcholine release during state dependent respiratory depression. AB - Microinjection of cholinergic agonists and acetylcholinesterase inhibitors into the medial pontine reticular formation (mPRF) causes a state that is polygraphically similar to rapid-eye-movement (REM) sleep. Respiratory studies of intact unanesthetized cats during this cholinergically induced REM sleep-like state have shown that the same cholinoceptive pontine reticular regions that mediate REM sleep can also cause state-dependent respiratory depression. The present study investigated the hypothesis that acetylcholine (ACh) release in the mPRF is increased during the respiratory depression that accompanies the cholinergically induced REM sleep-like state. Cats were implanted for polygraphic recording of sleep and wakefulness and with guide tubes aimed for placing a microinjector in one mPRF and a microdialysis probe in the contralateral mPRF. ACh release was measured with high-performance liquid chromatography and electrochemical detection. Compared with waking levels, ACh was significantly increased and respiratory frequency was significantly decreased during the carbachol-induced REM sleep-like state. These results support the hypothesis that endogenous cholinergic neurotransmission in brain regions known to regulate REM sleep can also cause state-dependent changes in respiratory control. PMID- 1887964 TI - Anticoagulant drugs and central nerve blockade. PMID- 1887965 TI - Induction and recovery characteristics of desflurane in day case patients: a comparison with propofol. AB - Desflurane is an ether halogenated exclusively with fluorine. It has a blood/gas partition coefficient of 0.42 (cf. isoflurane 1.40 and nitrous oxide 0.46). This characteristic suggests that it should provide both a fast induction of anaesthesia and a rapid recovery from anaesthesia. To assess this, 60 patients were entered into a study and allocated at random to one of four groups receiving either desflurane or propofol for induction and maintenance of anaesthesia. Desflurane caused loss of consciousness in approximately 2 minutes during gaseous inductions. The psychomotor scores in the patients who received propofol for induction and maintenance of anaesthesia were significantly worse compared with those who were given desflurane for either induction and maintenance or for maintenance only. There was also a tendency for other recovery parameters to be faster in the patients receiving desflurane although this did not reach statistical significance. This suggests that desflurane would be a suitable agent for day case anaesthesia providing for a rapid recovery. PMID- 1887966 TI - Lumbar regional anaesthesia and prophylactic anticoagulant therapy. Is the combination safe? AB - A survey has been carried out in all Danish anaesthetic departments (n = 80) regarding the attitude towards the use of epidural/spinal lumbar analgesia in patients who were receiving prophylactic anticoagulant therapy for the prevention of thromboembolism. About 60% of the departments used the techniques in patients receiving low-dose heparin and no side effects had been experienced. Spinal and epidural anaesthesia were in general regarded as being contraindicated in patients fully anticoagulated with vitamin K antagonists. In the world literature, the attitude towards the combination is conflicting. No randomised trial has been performed and complications are almost entirely confined to patients fully anticoagulated with vitamin K antagonists. Only one case of an epidural haematoma has been recorded when subcutaneous low-dose heparin was used as thromboprophylaxis. PMID- 1887967 TI - Comparison of the combined effects of atropine and neostigmine with atropine and edrophonium on the lower oesophageal sphincter. AB - In two groups (n = 11) of healthy patients, we have measured gastric, lower oesophageal and barrier pressures before and after antagonism of neuromuscular block during anaesthesia with nitrous oxide and isoflurane. In one group, atropine 1.2 mg and neostigmine 2.5 mg were given and in the second group atropine 0.6 mg with edrophonium 1 mg/kg. One minute after administration of the reversal agents, there was a significantly greater reduction in barrier pressures in the neostigmine and atropine group than in the edrophonium and atropine group, but subsequently, there was no significant difference between the two groups. We conclude that there is no clinical difference between the two reversal mixtures in terms of the risk of regurgitation in the immediate period after reversal. PMID- 1887968 TI - Cardiovascular effects of intravenous clonidine. Partial attenuation of the pressor response to intubation by clonidine. AB - The effect of clonidine on the pressor and heart rate response to tracheal intubation was studied in a placebo-controlled, randomised, double-blind trial. Thirty patients were pretreated with either clonidine 1.25 micrograms/kg, or clonidine 0.625 microgram/kg or an equivalent volume of normal saline, given intravenously 15 minutes before induction of anaesthesia. The attenuation of the pressor response to intubation of both clonidine groups was statistically significant compared to the saline group. Neither dose of clonidine completely abolished the increase in either heart rate or blood pressure. There was no difference in attenuation between the clonidine treatments; this indicated that the lower dose may be the more appropriate. PMID- 1887969 TI - Plasma catecholamine response to cataract surgery: a comparison between general and local anaesthesia. AB - We studied the plasma catecholamine, plasma glucose and cardiovascular responses to cataract surgery in 20 elderly patients allocated randomly to receive either general anaesthesia or local anaesthesia by retrobulbar block. Local anaesthesia prevented the increase in plasma noradrenaline, adrenaline and glucose concentrations found in those patients who received general anaesthesia and also improved cardiovascular stability. The results show the beneficial effects of local anaesthesia in preventing the hormonal, metabolic and cardiovascular changes found when cataract surgery is conducted under general anaesthesia. PMID- 1887970 TI - Oral ketamine. Its use for mentally retarded adults requiring day care dental treatment. AB - Four cases of severely mentally handicapped young adults requiring day care dental treatment are reported. All had required varying degrees of restraint during previous dental treatments, which had been distressing for the patient, the relatives and the ward staff. In all cases, administration of oral ketamine 10 mg/kg, 30-60 minutes before the procedure, facilitated subsequent induction of anaesthesia. PMID- 1887971 TI - Spondyloepiphyseal dysplasia congenita. Caesarean section under epidural anaesthesia. AB - Spondyloepiphyseal dysplasia congenita is a rare condition with several features of concern to the anaesthetist. The patients are of extremely short stature and the presence of kyphoscoliosis may lead to significant respiratory impairment. Cervical vertebral body changes can result in spinal cord compression and laryngotracheal stenosis may be present. The management of such a patient presenting for elective Caesarean section under epidural anaesthesia is described. PMID- 1887972 TI - Unilateral pulmonary oedema of the contralateral lung following transaxillary sympathectomy. AB - A previously healthy young male developed unilateral pulmonary oedema immediately after re-expansion of an intentionally collapsed lung after transaxillary sympathectomy. The pulmonary oedema was localised to the contralateral, uncollapsed lung. PMID- 1887973 TI - Thoracic epidural analgesia in a patient with bilateral phaeochromocytoma undergoing coronary artery bypass grafting. AB - A patient suffering from phaeochromocytoma and coronary artery stenoses needed coronary artery bypass grafting before adrenalectomy. High thoracic epidural analgesia (T1-T2) with bupivacaine and sufentanil in combination with general anaesthesia was used. Plasma adrenaline and noradrenaline concentrations decreased during the period before bypass grafting compared to the baseline value and no important haemodynamic changes were seen during this period. Thoracic epidural analgesia failed to suppress the release of catecholamine during the bypass period. After the operation, the plasma catecholamine concentrations returned to the baseline value. Excellent analgesia (visual analogue scale = 1-2) was achieved with a postoperative epidural, but the plasma catecholamine concentration increased considerably. PMID- 1887974 TI - The laryngeal mask airway. An unusual complication. AB - The laryngeal mask airway is an important addition to the anaesthetist's armamentarium, but its use is not without the possibility for misfortune. We encountered an unusual and potentially serious complication. A patient's epiglottis became trapped between the pliable grates in the mask portion of the laryngeal mask and partially obstructed his airway. Should this problem occur and remain unnoticed, in addition to the problem of airway obstruction during the anaesthetic, the oedematous epiglottis could be severely injured upon removal of the laryngeal mask. This, in turn, could result in airway obstruction requiring emergency treatment. PMID- 1887975 TI - Awake intubation: a new technique. AB - A 46-year-old male with a known history of difficult intubation presented for elective surgery. It was considered prudent to perform an awake intubation and a size 3 laryngeal mask was introduced under topical anesthesia. A gum elastic bougie was then passed, enabling the laryngeal mask to be removed and a tracheal tube to be inserted. PMID- 1887976 TI - Use of the Inspiron nebuliser during continuous positive airway pressure ventilation. AB - The Inspiron Nebuliser 002305 with air entrainment was assessed as a gas delivery device in a continuous positive airway pressure system. Inspired oxygen concentrations, total gas flows and pressures within the system were measured over a range of settings, with and without positive and expiratory pressure. Inspired oxygen concentrations and total flows were completely disrupted when a positive and expiratory pressure valve was applied, and the system failed to generate continuous positive airway pressure. We would not therefore recommend the Inspiron nebuliser as a gas delivery system for continuous positive airway pressure. PMID- 1887977 TI - Inaccuracy of pulse oximetry in patients with severe tricuspid regurgitation. AB - The accuracy of pulse oximetry was studied in a group of patients with severe tricuspid regurgitation. Measurements of arterial oxygen saturation from a finger and an ear probe were compared with those from a radial arterial blood sample analysed in vitro. Lower values were obtained using the pulse oximeter; the difference ranged from +2% to -11%. The discrepancies between pulse oximeter and laboratory oximeter readings were greater in this group of patients than in a control group who did not have tricuspid regurgitation. There was, however, no correlation between the magnitude of this discrepancy and either the peak central venous pressure or the venous pulse pressure. PMID- 1887978 TI - Faulty Superset plastic catheter mounts. A cautionary tale applicable to other mass-produced disposable products. AB - Nine Superset (Intersurgical Ltd) single-use corrugated plastic catheter mounts were found to be faulty in a boxed batch of 75. The manufacturer's meticulous system of batch coding enabled the source of the problem to be traced quickly. Sporadic faults must be expected to occur in mass-produced disposable equipment and the unusual origin of the defect reported in these catheter mounts is testimony to the way unexpected events can prejudice the most carefully regulated quality control. It is emphasised that the user can help safeguard the community by ensuring that stock is used in strict rotation and that batch numbers are accurately reported when faults arise. PMID- 1887979 TI - Whole blood electrolyte assay using ChemPro 500. A comparison of assay performance with standard laboratory instruments. AB - The ChemPro 500 'near-the-patient' analyser, with ChemPro 'Ion Profile' sensor cards, was evaluated for the assay of pH, Ca2+, K+ and Na+ in whole blood samples from patients in the intensive care unit or during surgery for heart or major blood vessel disease, or for liver transplantation. Imprecisions estimated from replicate whole blood measurements were much greater for all four ions than even the least stringent of the generally accepted analytical goals, and much greater than those estimated using quality assurance materials. Comparisons of assayed values with those obtained using standard laboratory instruments showed significant constant and proportional biases. The performance of the ChemPro 500 with the Ion Profile cards gave us no confidence in recommending their use to anaesthetists and intensivists. PMID- 1887980 TI - Harold King. A notable contributor to anaesthesia. AB - Harold King was an analytical chemist of distinction, who worked with Sir Henry Dale and his colleagues in the Medical Research Institute, later the Medical Research Council. He helped to quash the theory that the anaesthetic action of ether was attributable to its impurities. Interest in alkaloids led to the elucidation of the structure of hyoscine, the synthesis of muscarine and the first isolation of crystalline tubocurarine for which he proposed a structural formula, work which influenced Bovet in the synthesis of gallamine. He proposed the synthesis of the homologous series of methonium compounds which included relaxant and hypotensive drugs. His collaboration with Rosenheim was outstanding and opened the way for synthesis of cholesterol and the steroids. He was always encouraging clinicians, and gave a sample of tubocurarine to Ranyard West who was the first to inject d-tubocurarine into a human patient. PMID- 1887981 TI - Cardiovascular effects of nasotracheal intubation. AB - Intubation time, arterial pressure, heart rate and arterial oxygen saturation during nasotracheal intubation effected with the Macintosh laryngoscope blade were compared with those during orotracheal intubation. The 60 patients studied received a standardised general anaesthetic and were randomly allocated to one of two groups immediately before tracheal intubation. The mean nasal intubation time (33.2 seconds) was significantly greater than mean oral intubation time (14.8 seconds). The mean arterial pressure changes in the nasal group were significantly greater and more prolonged than in the oral group. The mean heart rate in the nasal group was significantly lower than in the oral group during the first minute after intubation, after which heart rates were similar. There were no significant differences between the two groups with regard to arterial oxygen saturation levels at any stage. PMID- 1887982 TI - Papaveretum infusions in infants under 6 months of age. AB - The effectiveness of a continuous low dose papaveretum infusion for the relief of postoperative pain was assessed in 29 infants aged 1-6 months nursed on the infant surgical ward following major abdominal surgery. Trained nursing staff were able to adjust the dosage within prescribed guidelines and satisfactory analgesia was obtained with a regimen which delivered up to 0.0375 mg/kg/hour, approximately half the dose recommended in children older than 12 months. There was one case of clinically significant respiratory depression. PMID- 1887983 TI - Pain on intradermal injection with lignocaine. The effect of concentration. AB - Twenty ASA 1 volunteers were each injected intradermally with four solutions containing 0.2 ml of 0.5%, 1%, and 2% lignocaine and 0.9% saline to determine whether the pain experienced on injection was related to the concentration of local anaesthetic. A 10 cm linear analogue pain scoring system was used, and the solutions were ranked from most painful to least painful. There were no differences between the different concentrations of lignocaine and 0.9% saline in the severity of pain experienced. We conclude that any concentration of lignocaine may be used intradermally before inserting intravenous catheters without affecting the degree of pain experienced by that injection. PMID- 1887984 TI - Awareness during caesarean section. PMID- 1887985 TI - A personal view of postdural puncture headache. PMID- 1887986 TI - Fault with an Ohmeda Excel 410 machine. PMID- 1887987 TI - Vaporizers--serviced and checked? PMID- 1887988 TI - Blood pressure recording during carotid endarterectomy. PMID- 1887989 TI - The oesophageal detector device. PMID- 1887990 TI - Anaesthesia for adults with congenital heart disease. PMID- 1887991 TI - Pulmonary artery wedge pressure in ARDS. PMID- 1887992 TI - Postoperative oxygen via the laryngeal mask airway. PMID- 1887993 TI - Laryngeal mask airway for coronary artery bypass grafting. PMID- 1887994 TI - Trainee anaesthetists and the laryngeal mask airway. PMID- 1887995 TI - The laryngeal mask and the oesophagus. PMID- 1887996 TI - Children's fingers and spurious pulse oximetry. PMID- 1887997 TI - Prilocaine associated methaemoglobinaemia and the pulse oximeter. PMID- 1887998 TI - Recurrent pleural effusions following superior vena cava thrombosis. PMID- 1887999 TI - Withdrawal syndrome after propofol. PMID- 1888000 TI - Inadvertant dural puncture during caudal anaesthesia for Saethre-Chotzen syndrome. PMID- 1888001 TI - Propofol in myotonic dystrophy. PMID- 1888002 TI - Ginger as an antiemetic: possible side effects due to its thromboxane synthetase activity. PMID- 1888003 TI - Masseter spasm in Williams syndrome. PMID- 1888005 TI - Fluorometric determination of carbohydrate with 2-aminothiophenol. AB - The 2-aminothiophenol-based fluorometric assay of Nakano et al. (1973, J. Pharm. Soc. Jpn. 93, 350-353) for monosaccharides has been modified to improve the speed, applicability, and sensitivity of the method. The improved assay is applicable to complex carbohydrates as well as to monosaccharides. Less than 50 ng of carbohydrate in a final volume of 2 ml can be quantitatively measured within 30 min. The assay is reasonably compatible with the presence of a variety of reagents commonly used in aqueous buffer solutions. The assay is especially useful for monitoring column eluents during the purification of small quantities of carbohydrates or their conjugates. PMID- 1888004 TI - n-Alkyl p-aminobenzoates as derivatizing agents in the isolation, separation, and characterization of submicrogram quantities of oligosaccharides by liquid secondary ion mass spectrometry. AB - In this laboratory we are pursuing a comprehensive strategy for isolation and characterization of oligosaccharides from glycoproteins that are available only in limited quantities. To improve sensitivity in the analysis by liquid secondary ion mass spectrometry, we have investigated the relative behavior of a homologous series of n-alkyl esters of p-aminobenzoic acid as derivatizing agents. Ethyl p aminobenzoate, the derivatizing agent used in many of our earlier studies, is one of these compounds. Our experiments using the hepatasaccharide maltoheptaose (M7) as a model oligosaccharide establish that by lengthening the alkyl chain from methyl to n-tetradecyl, a concomitant increase in the molecular ion abundance is obtained. The increase is a factor of 10 when 1 microgram of derivatized M7 is analyzed, and as much as 40 when 0.1 microgram of sample is examined. This series of derivatives of maltoheptaose form a suite of relatively abundant fragment ions in the negative ion mode as expected from our previous studies with the ethyl ester. Although very high mass spectral sensitivities were achieved with M7 n tetradecyl and n-decyl p-aminobenzoates, the yields of derivative obtained were significantly lower than those obtained for M7 n-octyl, n-hexyl, n-butyl, ethyl, and methyl p-aminobenzoates, despite improvements made in the derivatization procedure. When analyzing biological samples, n-octyl and n-hexyl p-aminobenzoate were found to be optimal considering both yield of derivative and mass spectral sensitivity. This improved method of derivatization was incorporated into a simple but effective procedure for dealing with very small quantities of heterogeneous samples of oligosaccharides, such as those released from 250 micrograms (1 nmol) of nicotinic acetylcholine receptor from Torpedo californica and 90 micrograms (2 nmol) of human alpha 1 acid glycoprotein. PMID- 1888006 TI - A method for eluting DNA in a wide range of molecular weights from agarose gels. AB - We have developed a simple and rapid method for recovering DNAs of a wide range of molecular weights from agarose gels. A DNA-containing gel slice is placed on a Parafilm sheet in the center of a circular (positive) electrode and covered with a drop of buffer, while a linear (negative) electrode is placed on the top of the gel and driven about 1 mm into the gel itself. When a continuous current is applied, the DNA migrates into the buffer toward the circular electrode. We have obtained almost total recovery of DNAs up to 10 kb in size. Our method may also be used, under appropriate conditions, for higher molecular weight DNAs. The yield and all the biological assays performed on the DNAs obtained by our method recommend it for routine laboratory use. PMID- 1888007 TI - Simultaneous determination of inosine, hypoxanthine, xanthine, and uric acid and the effect of metal chelators. AB - We describe a sensitive, reproducible method for the simultaneous determination of the ATP catabolites inosine, hypoxanthine, xanthine, and uric acid in biological samples and organ perfusate using reverse-phase chromatography and multiwavelength detection at 254, 270, and 292 nm. Sample preparation includes precipitating proteins with perchloric acid, neutralizing the sample, passing the supernatant over a polyethyleneimine column, and analyzing the collected fractions by high-performance liquid chromatography. Addition of metal chelators to the perchloric acid resulted in increased values for xanthine, hypoxanthine, and uric acid. The method was sensitive (limit of detection, 0.08 nmol on column; S/N = 4) and linear over the range 0.5-30 microM. Precision and accuracy of the method were evaluated for lung tissue and lung perfusate. Coefficients of variation ranged from 2.8 to 6.1% for perfusate and from 1.7 to 12.6% for tissue. Recoveries for all compounds exceeded 90%. We applied this method to rat lung tissue, lung perfusate, and rat and human blood. Advantages of this method are simultaneous quantitation with excellent sensitivity of all compounds, simplified peak identification by using multiwavelength detection, and improved accuracy by preventing loss of compounds with metal chelators. PMID- 1888008 TI - A microassay for proteolytic activity. AB - A quantitative procedure for measuring proteolytic activity, utilizing azoalbumin as substrate, has been developed for use in microtiter plates. An enzyme-linked immunosorbent assay reader is used to measure absorbance. The procedure is sensitive, as well as being both rapid and economical. It is particularly convenient for measuring large numbers of samples, such as fractions from column chromatography. PMID- 1888009 TI - Interference of biogenic amines with the measurement of proteins using bicinchoninic acid. AB - The use of bicinchoninic acid (BCA) to measure protein concentrations has received wide acceptance because the reagent is insensitive to many of the buffers, sucrose solutions and detergents used with various tissue and enzyme preparations. However, any compound capable of reducing Cu2+ in an alkaline medium such as biogenic amines will produce a color reaction. The primary objective of this study was to determine whether biogenic amines present in neuronal tissue would interfere with the measurement of protein using the BCA method. Catecholamines were found to produce a linear increase in color of the BCA reagent at concentrations between 1 and 100 nmol/2.1 ml assay volume. Catecholamines appeared to be more sensitive to the BCA reagent than either serotonin or ascorbic acid. Catecholamines at concentrations of 50 nmol/mg of protein or 1 nmol/2.1 ml assay volume or higher will produce significantly (P less than 0.0001) higher color reactions than protein alone. The BCA reagent is not ideal for measuring protein concentrations of intact synaptic vesicles and chromaffin granules since the catecholamine concentrations in these organelles are high enough to increase the color developed by 1.1 to 2.5 times that observed with protein alone. The linearity of the color development produced by catecholamines suggest that BCA could be used to quantitate catecholamine concentrations between 1 and 100 nmol. The BCA reagent will not distinguish between the different catecholamines. PMID- 1888010 TI - Anthranilamide and nitrotyrosine as a donor-acceptor pair in internally quenched fluorescent substrates for endopeptidases: multicolumn peptide synthesis of enzyme substrates for subtilisin Carlsberg and pepsin. AB - The preparations of N alpha-Fmoc-3-nitro-L-tyrosine and N-Boc-anthranilic acid Dhbt ester and their application to parallel multiple column solid-phase peptide synthesis is described. A series of peptide substrates containing an anthraniloyl group at the amino terminus and a 3-nitrotyrosyl residue close to the carboxyl terminus have been synthesized. The fluorescence of the anthraniloyl group, intramolecularly quenched by the 3-nitrotyrosine, increases with cleavage of peptide bonds situated between the two groups. The quenching mechanism is of the long-range resonance energy transfer type and long peptide substrates were constructed and used for kinetic measurement on subtilisin Carlsberg and pepsin. Complete quenching was observed even with more than 20 A between the centers of the chromophores, and substrates with up to 50 A between the chromophores were synthesized. The importance of long substrates for optimal enzymatic activity was demonstrated. PMID- 1888011 TI - A continuous fluorescence assay for protein kinase C. AB - A 6-acryloyl-2-dimethylaminonapthalene (acrylodan)-labeled 25-amino acid peptide (acrylodan-CKK-KKRFSFKKSFKLSGFSFKKNKK-COO-), containing the protein kinase C (PKC) phosphorylation sites of brain myristoylated alanine-rich kinase C substrate protein, undergoes a 20% fluorescence decrease when it is phosphorylated by phospholipid/calcium-dependent protein kinase (PKC). This fluorescence decrease is dependent on the presence of PKC, calcium (half-maximal stimulation at pCa = 6.2), phosphatidylserine, diacylglycerol, or phorbol-12 myristate-13-acetate (half-maximal stimulation at 2 nM) and ATP, and correlates well (r = 0.997) with [32P]phosphate incorporation into the peptide. This fluorescence assay allows detection of 0.02 nM PKC, while similar concentrations of cyclic AMP-dependent or type II calmodulin-dependent protein kinases produced no change in peptide fluorescence. The method can be used to assay purified PKC as well as activity in crude brain homogenates. Incubation of PKC with staurosporine inhibits the fluorescence decrease with an IC50 of 2 nM. Thus the fluorescence decrease that occurs in the acrylodan-peptide provides a continuous fluorescence assay for PKC activity. PMID- 1888012 TI - An o-toluidine method for detection of carbohydrates in protein hydrolysates. AB - The o-toluidine high-performance thin-layer chromatography (HPTLC) method for detection of reducing sugars has been demonstrated to be a facile method for composition analysis of protein hydrolysates with a maximum sensitivity range of 50-100 pmol. The solution phase reaction of o-toluidine with reducing sugars has been previously used for spectrophotometric detection of glucose at 480-630 nm. In contrast, the heterogeneous reaction of o-toluidine with reducing sugars resolved by thin-layer chromatography produces chromophoric derivatives which have a broad absorbance at 295 nm. Detection of these chromophoric derivatives is achieved by uv diffuse reflectance scanning densitometry. It is demonstrated that detection limits of less than 10 ng can be achieved by using HPTLC plates and is therefore equal or more sensitive for some sugars than recently reported high pressure liquid chromatography methods using amperometric or fluorescence detection. PMID- 1888013 TI - Synthesis and application of Fmoc-hydrazine for the quantitative determination of saccharides by reversed-phase high-performance liquid chromatography in the low and subpicomole range. AB - A new derivatization reagent, Fmoc-hydrazine, has been synthesized from the reaction of Fmoc-chloroformate with hydrazine as a precolumn fluorometric labeling reagent for reducing sugars such as glucose, galactose, mannose, fructose, fucose, ribose, xylose, arabinose, lactose, and maltose. The optimization of derivatization conditions was examined in detail. Using a reversed-phase high-performance C-8 column and a mobile phase consisting of acetonitrile-aqueous acetic acid, seven sugar derivatives were separated under either isocratic or gradient conditions within 20 min. The Fmoc-hydrazine and sugar Fmoc-hydrazone derivatives exhibit excellent stability. The extent of the hydrazone formation was 77 and 82% for mannose and fucose as assessed by Dionex high-performance anion-exchange chromatography with pulsed amperometric detection. Linear calibration graphs were established in the range from 0.5 to 2 pmol and 12 to 110 pmol for individual sugar derivatives. The determination limits were 0.05-0.09 pmol for mannose, galactose, and ribose; 0.1 pmol for maltose, xylose, and glucose; 0.2 pmol for fucose and lactose; 0.3 pmol for arabinose; and 0.4 pmol for fructose. The component monosaccharides of ultramicroquantities of two glycoproteins (e.g., from 7 ng fetuin and ovalbumin) were determined in the subpicomole range. PMID- 1888014 TI - High-performance liquid chromatographic determination of 1,2,3,4 tetrahydroisoquinoline in rat brain with fluorescence detection. AB - A high-performance liquid chromatographic method for the fluorometric determination of 1,2,3,4-tetrahydroisoquinoline in rat brain is described. 1,2,3,4-Tetrahydroisoquinoline and 4-phenylpiperidine (internal standard) are isolated by liquid-liquid extraction, and then converted into the corresponding fluorescent derivatives with 3,4-dihydro-6,7-dimethoxy-4-methyl-3-oxoquinoxaline 2-carbonyl chloride, a fluorescence derivatization reagent for amines. The derivatives are separated within 60 min on a reversed-phase column, TSK gel ODS 120T, with isocratic elution, and detected fluorometrically. The detection limit of 1,2,3,4-tetrahydroisoquinoline is 1.0 pmol/g in rat brain (S/N = 3). PMID- 1888015 TI - Selective precipitation of proteins from guanidine hydrochloride-containing solutions with ethanol. AB - The solubility of guanidine hydrochloride in ethanol and conversely the low solubility of proteins have been used as the basis for a procedure for recovering proteins from guanidine-containing solutions by selective precipitation. Yields of greater than 94% were observed with as little as 28 ng protein and of 98% for larger quantities of protein up to 20 mg/ml. The precipitations were independent of molecular weight for proteins in the range of 6-100 kDa and could be run in as little as 5 min at room temperature. Unlike the conventional desalting methods for removing guanidine, ethanol precipitation is rapid, efficient, and can be applied simultaneously to a large number of samples. The approach should have a wide range of applications. PMID- 1888016 TI - Determination of the epimeric composition of ibuprofenyl-CoA. AB - Ibuprofen [racemic2-(4-isobutylphenyl)propionic acid] is a 2-arylpropionic acid nonsteroidal anti-inflammatory drug which undergoes unidirectional, R to S chiral inversion in vivo. It has been proposed that this chiral inversion phenomenon occurs via a coenzyme A (CoA) thioester intermediate. To characterize the formation and metabolism of this metabolic intermediate, ibuprofenyl-CoA, reference standards were needed and thus the CoA derivatives of (R)-, (S)-, and racemic ibuprofen were chemically synthesized. An HPLC assay employing a C18 reverse-phase column was developed to quantitate "total" ibuprofenyl CoA. Samples collected from this assay were then analyzed for ibuprofenyl-CoA epimeric composition by chiral chromatography employing a Chiral-AGP alpha 1-acid glycoprotein column. The applicability of these methods was demonstrated by assessing (R)- and (S)-ibuprofenyl-CoA hydrolysis and epimerization following incubation with rat liver homogenates. Rat liver homogenate catalyzed the complete and rapid epimerization of ibuprofenyl-CoA and the rate constants for (R)- and (S)-ibuprofenyl-CoA hydrolysis were equal. ATP and CoA were found to inhibit rat liver-catalyzed ibuprofenyl-CoA hydrolysis by 70-80% with no effect on epimerization. Additionally, it was demonstrated that traditional indirect ibuprofenyl-CoA assays which employ basic hydrolysis result in erroneous epimeric ratio determinations due to chemical epimerization. PMID- 1888017 TI - Preparation and characterization of the NAD vinylogue, 3-pyridylacryloamide adenine dinucleotide. AB - The vinylogue of NAD, 3-pyridylacryloamide adenine dinucleotide, was prepared from NAD and 3-pyridylacryloamide through the snake venom NADase-catalyzed transglycosidation reaction. The analog, purified by ion-exchange chromatography, was obtained in a 55% yield. The cyanide adduct and reduced form of the analog exhibited absorbance maxima at 358 nm and 378 nm, respectively, with extinction coefficients in each case being 2.3-times higher than those reported for the corresponding NAD derivatives. 3-Pyridylacryloamide adenine dinucleotide served as a coenzyme with bovine liver glutamic dehydrogenase and to a lesser extent with malate and lactate dehydrogenases. The analog was not reduced in reactions catalyzed by yeast and horse liver alcohol dehydrogenases, sheep liver sorbitol dehydrogenase, and rabbit muscle glycerophosphate dehydrogenase. Substitution of the pyridylacryloamide analogs for NAD and NADH in the assay of substrates for glutamic dehydrogenase was demonstrated. PMID- 1888018 TI - Biological sulfane sulfur. AB - A voltammetric method for determining cyanide-reactive sulfane sulfur in biological materials is described. Samples are incubated with a sulfurtransferase, a thiolic cofactor, and cyanide. Thiocyanate formed and/or residual cyanide may then be determined electrochemically with either a silver rotating disk electrode or a dropping mercury electrode in differential pulse mode to provide estimates of sulfane sulfur content. The thiocyanate-based procedure is preferable, particularly when samples contain either serum albumin or inorganic sulfide. PMID- 1888019 TI - A method for the quantitation of hypericin, an antiviral agent, in biological fluids by high-performance liquid chromatography. AB - Hypericin, a polycyclic aromatic dianthroquinone, is a natural plant product with antiviral properties. We report here the development of a methodology for the extraction and quantitation of hypericin from plasma and biological fluids and the adaptation of a sensitive and selective method for detection of the compound by high-performance liquid chromatography. The methodology offers a rapid and specific means of monitoring drug blood levels in clinical and pharmacokinetic studies. The chromatographic procedure utilizes the substantial retentive properties of hypericin on reverse-phase media and detection by the strong visible absorbance maximum at 590 nm. Verification by the fluorescence spectral properties of hypericin in organic media can also be utilized. The assay is linear over a 3 log concentration range and hypericin is consistently recovered from murine, simian, and human plasma. The methodology was applied to assess the pharmacokinetic properties of hypericin in mice receiving a single bolus injection of 350 micrograms. A distribution half-life of 2.0 h and an elimination half-life of 38.5 h were calculated. We also discuss the limitations of direct analysis of hypericin by absorbance or fluorescence measurements. PMID- 1888020 TI - Continuously recording fluorescent assays optimized for five human matrix metalloproteinases. AB - Four new fluorogenic heptapeptide substrates have been synthesized with sequences that are optimized for five human matrix metalloproteinases (MMP). All four substrates are similar to one recently reported by Stack and Gray (1989, J. Biol. Chem. 264, 4277-4281) and have the fluorescent Trp residue in subsite P'2 and the dinitrophenol (DNP) quenching group on the N-terminus. The quenching of the Trp fluorescence in the intact substrate is relieved on hydrolysis of the P1-P'1 bond, giving rise to a continuously recording fluorescence assay. The residues placed in subsites P3-P'1 and P'3 have been optimized for each MMP, while Arg has been placed in P'4 to enhance solubility. Thus, DNP-Pro-Leu-Ala-Leu-Trp-Ala-Arg has been prepared as a substrate for fibroblast collagenase, DNP-Pro-Leu-Ala-Tyr Trp-Ala-Arg for neutrophil collagenase, DNP-Pro-Tyr-Ala-Tyr-Trp-Met-Arg for neutrophil collagenase, DNP-Pro-Tyr-Ala-Tyr-Trp-Met-Arg for stromelysin, and DNP Pro-Leu-Gly-Met-Trp-Ser-Arg for both 72-kDa fibroblast gelatinase and 92-kDa neutrophil gelatinase. These substrates have been characterized with respect to their composition, solubility, optical and fluorescence spectra, and hydrolysis by their target MMP. The hydrolysis rates rival or exceed those of either their natural protein substrates or other synthetic peptides. The solubility of each substrate in assay buffer exceeds the KM value for each reaction, allowing accurate determination of the kinetic parameters. These new substrates should greatly facilitate kinetic studies of the MMP. PMID- 1888021 TI - Miniaturization of three carbohydrate analyses using a microsample plate reader. AB - Three carbohydrate analyses (reducing value by copper-bicinchoninate, total carbohydrate by phenol-sulfuric acid, and D-glucose by glucose oxidase) have been miniaturized using a microsample plate reader. The use of the reducing-value procedure to measure the hydrolysis of starch by alpha-amylase and the use of the glucose oxidase method to measure the hydrolysis of lactose by lactase are illustrated. PMID- 1888022 TI - A coupled assay for bile acid:CoA ligase. AB - A new assay for the enzyme bile acid:CoA ligase is presented. The new assay is designed to supplant the existing radiometric assays which require radiolabeled bile acids. The new assay couples the formation of bile acid-CoA to its glycination in a reaction catalyzed by bile acid-CoA:glycine N-acyltransferase. The coupling reaction utilizes [14C]glycine and the bile acid-CoA is quantitatively converted to [14C]glycobile acid. The [14C]glycobile acid is isolated by solvent extraction and quantitated by liquid scintillation counting. The method is shown to be accurate, highly sensitive, and applicable to a wide variety of bile acids. PMID- 1888023 TI - Determination of platelet-activating factor and alkyl-ether phospholipids by gas chromatography-mass spectrometry via direct derivatization. AB - A mass spectrometric method has been developed for the quantitative analysis of platelet-activating factor (PAF) and lyso-platelet-activating factor (lyso-PAF) based on electron-capture gas chromatography-mass spectrometry using a stable isotope dilution technique. The cleavage and derivatization was accomplished in a single step by direct reaction of phospholipid with pentafluorobenzoyl chloride at 150 degrees C. Spectroscopic and chromatographic data indicated that PAF and lyso-PAF were converted into derivatives containing a pentafluorobenzoyl group in place of the original phosphocholine group with 95 and 51% yield, respectively. Additionally, in the lyso-PAF derivative, the free hydroxyl group was found to be replaced by chlorine. Phosphatidylcholines containing an arachidonoyl group can be derivatized with a solution of PFBCl/chloroform at 120 degrees C for 18 h, producing 90% derivative. Analysis by GC/MS and LC/MS allowed the detection of 1 or 250 pg derivative, respectively, injected onto the column with S/N greater than 3. Newly available analogues of high isotopic purity containing either three or four deuterium atoms located in the 1-O-hexadecyl chain were used as internal standards. The developed GC/MS assay was used to quantitate PAF and lyso-PAF in rabbit leukocytes before and after stimulation with calcium ionophore. The levels of PAF in unstimulated cells were in the order of 2.27 pmol/10(6) cells and increased about 17-fold during 10-min stimulation with 2 microM ionophore A23187. The lyso-PAF levels in resting cells were in the order of 3.76 pmol/10(6) cells and increased 1.7-fold during stimulation. This assay exhibited satisfactory sensitivity, reproducibility, and accuracy. PMID- 1888024 TI - Quantitative determination of albumin in urine by on-line immunoadsorptive cleanup and reversed-phase chromatography. AB - Albumin in urine is selectively adsorbed on an immunoadsorber (human serum albumin-specific antibodies coupled covalently with a silica stationary phase) and after elution with 0.1% HCl is quantitatively determined by reversed-phase chromatography with detection of native fluorescence. The optimization of sample preparation and characteristics of the method such as recovery, linearity, reproducibility, detection limit, and selectivity are discussed. PMID- 1888025 TI - A mass spectrometry method for mapping the interface topography of interacting proteins, illustrated by the melittin-calmodulin system. AB - The shielding of lysine groups from acetylation by acetic anhydride has been used to identify the regions of calmodulin in contact with melittin in the 1:1 complex. The estimation of the degree of acetylation was done by examining cyanogen bromide and cyanogen bromide/trypsin digests by mass spectrometry. Evidence was obtained that lysines-21, -75, and -148 are protected to some extent, with the implication that both the N- and C-terminal lobes and the connecting strand are involved in the interaction. PMID- 1888026 TI - Quantitative high-performance liquid chromatography analysis of DNA oxidized in vitro and in vivo. AB - Oxidative modification of genetic material has been implicated as a factor in carcinogenesis, particularly during promotion and progression, and therefore there is a need for sensitive detection of oxidized DNA bases. We developed a method that can be applied to DNA isolated from any source and used to simultaneously quantify oxidized nucleosides without a need to prelabel the DNA or use destructive hydrolytic procedures. This method is based on: (a) enzymatic DNA digestion; (b) HPLC separation of the resultant nucleosides; (c) acetylation of the oxidized nucleosides with [3H]Ac2O (acetic anhydride); (d) removal of the radioactive debris; and (e) quantitative analysis of tritiated nucleoside acetates by HPLC. Enzymatic DNA digestion was optimized using DNase I in the presence of Mg2+ (pH 7), followed by nuclease P1 in the presence of Zn2+ (pH 5.1) and alkaline phosphatase (pH 7.5). Analysis of DNA oxidized with H2O2 in the presence of Fe2+/EDTA for 30 min showed that the levels of 8-OHdG (8-hydroxy-2' deoxyguanosine) were increased 2.7-fold, HMdU (5-hydroxymethyl-2'-deoxyuridine) 3.15-fold, and FdU (5-formyl-2'-deoxyuridine) 2.5-fold. Although the (-)-isomer of cis-dTG (cis-thymidine glycol) was enhanced 2.3 times, the (+)-isomer remained virtually unchanged. Analysis of DNA isolated from epidermal cells of mice treated in vivo with the tumor promoter TPA (12-O-tetradecanoylphorbol 13 acetate) showed 4.8-, 2.7-, and 8.7-fold increases in the levels of total cis dTG, 8-OHdG, and HMdU, respectively, and of some unknown DNA oxidation products. These results prove applicability of the 3H-postlabeling method to the analysis of DNA (and potentially RNA) isolated from many sources, including animals and humans. PMID- 1888027 TI - The direct measurement of protein kinase C (PKC) activity in isolated membranes using a selective peptide substrate. AB - A protein kinase C (PKC)-selective peptide substrate was used to develop a method for measuring PKC activity directly and quantitatively in isolated cell membranes without prior detergent extraction and reconstitution of the enzyme with phosphatidylserine and TPA in the presence of excess Ca2+. This simple and rapid method can reliably measure changes in membrane-associated PKC activity induced by various bioactive compounds such as hormones and growth factors. Also, this method, which measures PKC activity in its native membrane-associated state, has the advantage of being able to distinguish between active and inactive PKC associated with cell membranes. PMID- 1888028 TI - Filter screening of antibody Fab fragments secreted from individual bacterial colonies: specific detection of antigen binding with a two-membrane system. AB - Recently antibody fragments have been expressed in a functional form from bacteria. We have devised a simple method to detect the binding of antigen to antibody Fab fragments secreted by bacterial colonies. Bacteria harboring plasmid vectors that direct the secretion of Fab fragments into the bacterial periplasm are grown on one membrane. The secreted fragments are allowed to diffuse to a second "capture" membrane coated with anti-globulin, and are probed with antigen. Using enzyme or colloidal gold conjugates, the binding of antigen is detected on the second membrane as a colored spot. The colonies can be regrown on the first membrane, and the antigen binding signal on the second membrane is free of noise contributed by bacterial debris. PMID- 1888029 TI - Analysis of mutant tRNA gene transcripts in vivo in Saccharomyces cerevisiae by abortive primer extension. AB - When the primer extension of a synthetic oligonucleotide hybridized to a complementary region of RNA is made in the presence of only three deoxyribonucleosides triphosphates, elongation of the primer stops as soon as the missing nucleotide is needed. This abortive primer extension assay has been adapted to analyse tRNA gene transcripts and has two main advantages. First it is specific and allows the identification of particular tRNA gene products in an homologous system provided the gene bears a point mutation. Second, it is highly sensitive and can be used to complement and confirm results of Northern blot hybridization. This assay should be a useful tool in the further in vivo study of the transcription and processing of particular tRNA genes in the homologous system. In this report the expression of wild-type and mutant yeast Sup4- tyrosine inserting suppressor gene was studied. PMID- 1888030 TI - Separation by capillary electrophoresis followed by dynamic elution. AB - In this study we have explored the behaviour of peptides after capillary electrophoresis (CE) followed by elution under pressure. The use of D2O- rather than H2O-based buffer solutions appears to restrict the diffusion of peptides after CE, resulting in little loss of resolution when peptides are eluted by dynamic flow. In this paper we present results showing that a simple two-step process, involving CE at a low voltage, switching off the power supply, and connecting the fused capillary at the anode end to a syringe pump for dynamic flow, can retain separation characteristics and can be used for the isolation of picomole quantities of peptides for sequence determination. PMID- 1888031 TI - A reversed-phase ion-pair high-performance liquid chromatography method for bovine testicular hyaluronidase digests using postcolumn derivatization with 2 cyanoacetamide and ultraviolet detection. AB - A reversed-phase ion-pair HPLC method for separating hyaluronic acid oligomers, using a polymeric C18 column at alkaline pH, is described. As the concentration of the ion-pairing agent tetrabutylammonium hydroxide increased, over the range of 0.01 to 0.06M, the capacity factors (k') of tetra- to dodecasaccharide decreased. The change in k', for each increment in pairing agent, increased with oligomer molecular weight. When changing mobile phase pH from 7 to 8, k' dramatically decreased and remained unchanged from pH 8 to 11. The isocratic separation was optimized to resolve tetrato dodecasaccharide at pH 9.0 in under 19 min. The postcolumn derivatizing agent 2-cyanoacetamide reacted with the reducing N-acetylglucosamine end groups of hyaluronic acid oligomers to yield reaction products that were monitored at 27 nm. In a series of control experiments using decasaccharide and N-acetylglucosamine, it was found that maximum product formation took place at pH 9 and was greatly influenced by borate buffer concentration. The optimum concentration for 2-cyanoacetamide was 0.33% and a temperature of 100 degrees C gave the best signal to noise ratio for the postcolumn reaction. The method is linear and reproducible, and has a lower limit of detection for tetrasaccharide of 20 ng (25 pmol). This system is suitable for studying the degradation kinetics of purified hyaluronic acid oligomers by bovine testicular hyaluronidase. Extension of the method to fluorescent and electrochemical detection and its applicability to other glycosaminoglycans is discussed. PMID- 1888032 TI - Development of an acid-soluble assay for measuring retrovirus integrase 3'-OH terminal nuclease activity. AB - A quantitative and efficient assay was developed to measure the 3'-OH terminal DNA endonuclease activity of the avian myeloblastosis virus (AMV) integrase protein. A retroviral-like linearized plasmid containing long terminal repeat (LTR) sequences at its recessed 3'-OH termini was filled in and labeled with the Escherichia coli Klenow DNA polymerase fragment. The 32P-labeled nucleotide was located at the penultimate position. The labeled linearized plasmid or restriction fragments derived from it were incubated with AMV IN and release of the label was quantitated by conversion to acid-soluble counts. The structure of the released product was characterized on 23% sequencing gels. Results indicate that AMV integration protein is functioning as an endonuclease releasing a dinucleotide and that the activity is stoichiometric with a preference for the cleavage of the U3 LTR terminus over that of the U5 LTR terminus. PMID- 1888033 TI - Gel electrophoresis of reacting macromolecules. Rate-limited self-association. AB - Prompted by experimental sodium dodecyl sulfate-gradient polyacrylamide gel electrophoresis (PAGE) patterns of an oligomerizing 73-residue peptide, PAGE and gradient PAGE patterns were simulated numerically for two rate-limited, reversible self-associating systems, viz., monomer-dimer and monomer-dimer tetramer interactions. A wide range of values for rate constants and other relevant parameters was examined. The cardinal result for interactions with half times comparable to the time of electrophoresis is that the number of peaks in the pattern can exceed the number of interacting species. Since peaks of intermediate migration velocities are composed of interconverting monomer and oligomers, molecular weights corresponding to individual species cannot be assigned to them. PMID- 1888034 TI - Transpeptidation during the analytical proteolysis of proteins. AB - Since peptide mapping with proteolytic enzymes such as trypsin and Staphylococcus aureus V8 protease is a powerful tool for the characterization of proteins, investigators should be cognizant of possible artifacts due to the technique itself. This article describes the identification of minor peaks found in the maps of recombinant human relaxin and insulin-like growth factor I as transpeptidation products. Both proteins have some homology to insulin with relaxin being composed of two chains designated A and B, while insulin-like growth factor I is composed of a single polypeptide chain. Digestion of relaxin with trypsin at pH 7.2 yields two peptides, T2,3(A10-18) and T7(B10-13), linked together by a disulfide bond. An unexpected component at a 10% level was identified to be the T2-T7 peptide pair where T3(ArgA18) has formed a peptide bond with the amino-terminal LeuB10 of the T7 peptide. It was also observed that the digestion of insulin-like growth factor I with V8 protease normally yields two peptides V4(13-20) and V9(59-70) linked by a disulfide bridge. A minor peak at a 1 to 2% level was identified to be a single polypeptide resulting from the formation of a peptide bond between the amino-terminal Met59 of V9 and the carboxyl-terminal Asp20 of V4, with the disulfide bond intact. These transpeptidation products were isolated by reversed-phase HPLC and identified using amino-terminal sequence and mass spectrometric analyses. PMID- 1888035 TI - Large-scale preparation of asymmetrically labeled fluorescent lipid vesicles. AB - A method for producing lipid vesicles containing fluorescent phospholipid analogues localized to the inner leaflet of their membrane was developed. Incubation of a 450-fold molar excess of serum albumin with lipid vesicles symmetrically labeled with 1 mol % 1-palmitoyl-2-(N-4-nitrobenzo-2-oxa-1,3 diazolyl)amino-caproyl phosphatidylcholine resulted in the removal of 99% of the fluorescent lipid from the outer leaflet. Asymmetrically labeled vesicles were separated from albumin/lipid complexes by gel filtration chromatography. Vesicles prepared in this manner were unable to transfer fluorescent lipid to cells during liposome-cell incubations. Liposomes asymmetrically labeled with other 4 nitrobenzo-2-oxa-1,3-diazole (NBD)-phospholipid analogues were also prepared. Removal of amino-dodecanoyl-NBD-labeled lipids from the outer leaflet of liposomes required three times more bovine serum albumin, and 48 h of incubation. This method can be used to produce large amounts of asymmetrically labeled liposomes suitable for use in investigating a variety of membrane phenomena. PMID- 1888036 TI - Quantitation of type I, III, and V collagens in human tissue samples by high performance liquid chromatography of selected cyanogen bromide peptides. AB - A method to determine the proportions of the major fiber-forming collagens (types I, III, and V) in noncartilaginous human tissues is presented. The procedure relies on direct solubilization of tissue collagen as cyanogen bromide peptides. The peptides are subjected to cation exchange chromatography followed by gel permeation chromatography in a manner consistent with the rapid resolution and quantitation of relatively low-molecular-weight marker peptides for each collagen. The marker peptides utilized for type I, III, and V collagens are alpha 1 (I)-CB2, alpha 1 (III)-CB2, and alpha 1 (V)-CB1, respectively. Quantitation of the peptides is attained as a function of ultraviolet absorbance during gel permeation chromatography. The nature of the marker peptides, the use of high performance liquid chromatography techniques, and quantitation of the peptides by ultraviolet absorbance renders the method suitably rapid, sensitive, and accurate for routine evaluations of collagen composition. The utility of the method is illustrated in the presentation of analyses on specimens of placental membranes and blood vessel walls. PMID- 1888037 TI - Detection apparatus for multiple heterogeneous chemiluminescence immunoassay configurations. AB - We describe an apparatus for measuring signals emanated from two heterogeneous chemiluminescence immunoassay (CLIA) configurations: antibody-coated polystyrene beads, in reaction tray wells, and microparticles captured by a porous matrix. An optics and fluidics design which allows the use of a common detection head for these two different assay configurations is described. The detection head moves along three Cartesian coordinates to create a localized light-tight compartment around each individual disposable reaction vessel. Reproducibility of the light seal, trigger solution delivery, and mixing is achieved for acridinium-labeled CLIA. The coated polystyrene beads configuration is tested using beta HCG, CEA, and TSH assays. The microparticle-capture configuration is tested using beta HCG and HBsAg assays. The microparticle capture CLIA has shorter incubation times and the potential for ease of automation. PMID- 1888038 TI - Quantitative study of protein association at picomolar concentrations: the lambda phage cl repressor. AB - A method has been developed for radiolabeling the lambda cl repressor to a specific activity sufficiently high to permit accurate quantitation of the protein in the picomolar range of concentration. Procedures are described whereby the labeled protein can be used for accurate quantitative study of the energetics of repressor assembly by large zone analytical gel chromatography. This methodology is applicable to other systems in which the stoichiometry and energetics of tightly associating DNA binding proteins are currently difficult to measure. PMID- 1888039 TI - Nondenaturing protein electrotransfer of the esterase activity of lipolytic preparations. AB - Lipolytic enzymes subjected to nondenaturing polyacrylamide gel electrophoresis were electrophoretically transferred under nondenaturing conditions onto a solid state matrix. Electrotransfer permitted the visualization of hydrolytic activity to the long-chain water insoluble substrate alpha-naphthyl palmitate. Four commercial preparations: a lipase from Candida cylindracea, an esterase from porcine liver, a lipase from Pseudomonas sp., and a cholesterol esterase from Pseudomonas fluorescens were examined. PMID- 1888040 TI - Fluorometric determination of plasma adenosine concentrations using high performance liquid chromatography. AB - Methods are described for the fluorometric determination of plasma adenosine concentrations, using HPLC. Plasma obtained from blood of dogs treated with erythro-(2-hydroxy-3-nonyl)adenine hydrochloride and dipyridamole was deproteinized with perchloric acid and the neutralized sample was put sequentially onto a SepPak C18 and boronic acid affinity column. Subsequently, adenosine in the final elution was converted to 1,N6-ethenoadenosine and was quantitated by HPLC with a fluorescence detector. The percentage recovery of adenosine added to the deproteinized plasma was nearly 100%. In the adenosine deaminase treated plasma, the increase in adenosine concentration of even 4 nM can be accurately determined. The control renal venous plasma concentrations of adenosine in anesthetized dogs were 19.9 +/- 1.9 nM, a significantly higher value than the corresponding arterial concentrations (12.7 +/- 1.1 nM), thereby suggesting the renal release of adenosine. This release was markedly enhanced following the removal of the renal arterial occlusion. Thus, taken together with the in vivo results, the present method is sensitive, hence most useful for the determination of plasma adenosine concentrations. PMID- 1888041 TI - Quantitative determination of mRNA phenotypes by the polymerase chain reaction. AB - A method for quantitative determination of specific cellular mRNA is described. The mRNA in a dilution series of total RNA was reverse transcribed by an oligo-dT primer and the cDNA was amplified by the polymerase chain reaction (PCR) using sets of specific primers. A 32P- or biotin-labeled specific probe was hybridized to the PCR products immobilized on nitrocellulose membrane. The intensity of the hybridization signals was evaluated for quantification of the PCR products. A standard curve was produced by the known amount of the in vitro transcribed cRNA, which contained the same sequence as the mRNA. The series of standard cRNA dilutions were reverse transcribed, amplified and hybridized in the same manner. The amount of the specific RNA was deduced by fitting to the standard curve. Two tissue specimens of intestinal tumors, evaluated on the basis of hybridization signals by three different methods, were shown to contain similar amounts of beta actin mRNA. Furthermore, a Chinese hamster ovary (CHO) cell line transfected with platelet-derived growth factor (PDGF) beta-receptor cDNA was found to contain similar amounts of beta-actin mRNA as the untransfected CHO cell line. However, the transfected CHO cell line contained over 10(11) copies of the PDGF beta receptor mRNA per microgram of total RNA, while the untransfected one showed no detectable RNA, indicating that the latter contained less than 10(6) copies per microgram of total RNA in this assay. PMID- 1888042 TI - Separation of phytanic and pristanic acid by high-pressure liquid chromatography: application of the method. AB - The synthesis of pristanic acid from phytanic acid, and a simple reversed-phase high-pressure liquid chromatographic (HPLC) method for the separation and purification of these acids, is described. A base-line separation of [U 3H]phytanic and [U-3H]pristanic acid is achieved with a graphitized carbon column. The isoprenoid metabolites formed after incubation of cultured fibroblasts with phytanic or pristanic acids are extracted with a Sep-Pak C18 cartridge and separated from the substrates by the same reversed-phase HPLC used for substrate purification. The methods are suitable for studies on the mechanisms for degradation of phytanic acid. Recently, different inborn errors with accumulation of phytanic acid have been defined. The present method will be a useful tool in our efforts to define these metabolic defects and their subcellular localization. PMID- 1888043 TI - A dot-blot assay for quantitation of nanogram amounts of protein in the presence of carrier ampholytes and other possibly interfering substances. AB - A method for protein determination in one- and two-dimensional electrophoresis sample buffer is presented. Accurate quantitation of protein in two-dimensional electrophoresis sample buffer (9.5 M urea, 2% Nonidet P-40, 2% carrier ampholytes, and 5% 2-mercaptoethanol) required removal of carrier ampholytes prior to the assay. This was made possible by taking advantage of the mutual solubility/insolubility of carrier ampholytes/proteins in saturated ammonium sulfate solution. In addition, improvement of protein determination in denaturing electrophoresis sample buffer containing the anionic detergent sodium dodecyl sulfate and the reducing agent 2-mercaptoethanol was achieved. The assay covers a range of sensitivity from 40 ng to 20 micrograms of protein. The procedure is applicable to large numbers of samples. PMID- 1888044 TI - Acute ventricular wall motion heterogeneity. A valuable but imperfect index of myocardial ischemia. PMID- 1888045 TI - The automated interview versus the personal interview. Do patient responses to preoperative health questions differ? AB - Laboratory testing of presurgical patients has been shown to be excessive, thereby increasing costs, reducing resources for other health care uses, and increasing risks to both patients and physicians. As one step toward reducing the number of unnecessary preoperative tests ordered, we used an automated method to aid preoperative assessment of 239 patients in Chicago and in Winnipeg. The "HealthQuiz," a small hand-held device containing a computer chip and video screen, uses a decision tree to ask a minimum of 60 health-related questions (the patient's response to certain questions determines the number of questions presented). The device then generates a summary printout of patient answers, the health areas needing further attention, and the laboratory tests most likely to uncover clinically important abnormalities in that patient. HealthQuiz responses are intended to aid the physician and not to replace the personal interview. As an aid, the automated interview highlights possible problem areas for in-depth pursuit by the physician. The need for nonselective batteries of tests is eliminated because recommendations for tests are based on specific elements of a patient's history. To be effective, responses to the HealthQuiz should be the same as responses to similar questions asked by a physician. We tested that premise in this study. Patient's answers to the HealthQuiz were compared with their responses to a randomly selected set of the same questions in a personal interview. Ninety-seven percent of the response pairs were identical, and most of the 3% that differed involved changes from "not sure" replies to the HealthQuiz. Laboratory tests suggested by responses to the two methods of questioning did not differ.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1888046 TI - The effect of intrathecal morphine on somatosensory evoked potentials in awake humans. AB - Although the effect of systemic opioids on somatosensory evoked potentials has been well described, little is known about the interaction between intrathecally administered opioid analgesics and somatosensory evoked potentials. Accordingly, the influence of intrathecally administered morphine on posterior tibial nerve somatosensory cortical evoked potentials (PTSCEPs) was investigated in 22 unpremedicated, awake, neurologically normal patients scheduled to undergo elective abdominal or pelvic procedures. Patients were randomly assigned to receive either preservation-free intrathecal morphine sulfate (ITMS) or placebo. After baseline PTSCEP, heart rate and, mean blood pressure were recorded, ITMS (15 micrograms.kg-1) was injected via standard dural puncture with the patient in the lateral position. PTSCEPs, heart rate, and mean blood pressure were recorded again at 5, 10, 20, 30, 60, 90, and 120 min. Control patients were treated identically (including position, sterile preparation, and subcutaneous tissue infiltration with local anesthetic), except for lumbar puncture, and were unaware of their randomization. Before administration of ITMS, PTSCEP P1, N1, P2, N2, and P3 latencies were 39.4 +/- 3.2, 47.6 +/- 3.9, 59.2 +/- 3.2, 70.4 +/- 3.7, and 84.6 +/- 5.5 ms, (mean +/- standard deviation), respectively. The corresponding P1-N1, N1-P2, and P2-N2 amplitudes were 2.4 +/- 1.1, 2.4 +/- 1.1, and 2.3 +/- 0.9 microV, respectively. There were no significant changes over time between the control and ITMS groups. PTSCEPs resulting from left-sided stimulation were not different from those elicited by right-sided stimulation. All ITMS patients had intense postoperative analgesia for at least 24 h. It is concluded that ITMS does not affect PTSCEP waveforms in the 35-90 ms latency range during the awake state.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1888047 TI - Fetal heart rate after epidural lidocaine and bupivacaine for elective cesarean section. AB - This prospective double-blind study was designed to determine whether the fetal heart rate (FHR) changes that have been reported after epidural administration of bupivacaine and lidocaine during labor are present when larger doses of these drugs are given during elective cesarean section. Prior to inserting an epidural catheter, FHR and maternal vital signs were monitored during a control period in 60 healthy term parturients. Patients were randomly assigned to receive either 0.5% bupivacaine with 0.1 mEq sodium bicarbonate added to each 20 ml (n = 30) or 2% lidocaine with 1:300,000 epinephrine (n = 30). A 3-ml test dose of the study solution was injected via the catheter and was followed by an additional 17 ml, in increments; additional doses were administered as necessary to obtain surgical anesthesia. FHR and maternal vital signs were monitored for at least 20 min and the characteristics of the anesthetic block noted. At delivery, neonatal status was evaluated, and maternal and cord blood samples were obtained for local anesthetic assays and neonatal blood gases. The groups were similar with respect to maternal characteristics, onset of surgical anesthesia, time to delivery, and uterine incision-delivery interval. Maternal blood pressure decreased from control values in both groups (P less than 0.05), but there was no difference between the groups in either the incidence of hypotension or ephedrine requirements. Analysis of FHR tracings by a perinatologist blinded to the study group revealed no changes after anesthesia and no significant differences between the groups at any time in basal FHR, short- or long-term variability, or the incidence of accelerations or decelerations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1888048 TI - Effect of epidural clonidine on analgesia and pharmacokinetics of epidural fentanyl in postoperative patients. AB - Epidural clonidine produces postoperative analgesia in patients and potentiates opioid analgesia in animals. The aim of the current study was to assess the effect of epidural clonidine on the plasma concentrations and analgesic effect of fentanyl after epidural administration. Twenty ASA physical status 2 or 3 patients recovering from abdominal surgery were allocated randomly to receive either epidural fentanyl (100 micrograms in 10 ml isotonic saline; EF group) or epidural fentanyl (same dose) plus epidural clonidine (150 micrograms; EF + C group) in isotonic saline solution. Analgesia was assessed over a period of 12 h after epidural injection. Venous samples were obtained until 360 min after epidural injection for radioimmunoassay determination of plasma fentanyl concentration. Onset of analgesia was similar in the two groups of patients (13 +/- 6 and 13 +/- 3 min, respectively, after injection), but duration was more than doubled in the patients receiving clonidine (543 +/- 183 vs. 250 +/- 64 min). Peak plasma fentanyl concentrations (Fmax) and the time to reach Cmax (Tmax) were comparable in the two groups (0.29 +/- 0.15 ng.ml-1 at 16.2 +/- 14.8 min in the EF group and 0.27 +/- 0.11 ng.ml-1 at 8.3 +/- 5.5 min in the EF + C group), as were plasma concentrations at each definite time of measurement. Drowsiness and hypotension were noticed in the EF + C group. Thus, epidural clonidine appears to prolong epidural fentanyl analgesia without affecting its plasma concentration. PMID- 1888049 TI - Assessment of myocardial perfusion during CABG surgery with two-dimensional transesophageal contrast echocardiography. AB - No reliable, quantifiable index of tissue perfusion is currently available to assess the efforts of coronary artery bypass graft (CABG) surgery. We used two dimensional transesophageal contrast echocardiography with sonicated Renografin 76 microbubbles to determine the distribution of myocardial blood flow during coronary artery bypass graft surgery in 15 patients. Sonicated Renografin-76 contrast agent was injected into the aortic root of all patients after institution of cardiopulmonary bypass and application of the aortic occlusive clamp. Eight patients had contrast agent injected directly into the free proximal end of the vein-CABG anastomosis. All patients again received aortic root injections during reperfusion after anastomosis of the proximal aortovein and distal coronary artery. Echocardiographic images of the left ventricle short axis at the level of the papillary muscles were obtained in real time and analyzed retrospectively from videotape. Injection of contrast provided information about the magnitude and geometric distribution of coronary artery-vein bypass run-off and enabled identification of poorly perfused myocardial regions. When predicted myocardial perfusion patterns, based on preoperative evaluation of epicardial vessel distribution derived from coronary angiography, were compared to actual perfusion patterns assessed with intraoperative echocardiography, contrast regional myocardial perfusion patterns were predicted 84% of the time (71-97%, 95% confidence limit). Regional myocardial perfusion deficits detected after coronary bypass grafting were associated with regional wall motion abnormalities detected after separation from cardiopulmonary bypass. Our technique makes possible on-line visualization of changes in regional blood flow in the heart before, during, and after CABG.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1888050 TI - Respiratory, laryngeal, and tracheal responses to nasal insufflation of volatile anesthetics in anesthetized humans. AB - In order to determine whether or not irritation of the nasal passage with commonly used volatile anesthetics can elicit airway reflexes, we investigated respiratory, laryngeal, and tracheal responses to nasal insufflation of three volatile anesthetics (enflurane, isoflurane, and halothane) in 13 patients anesthetized with flunitrazepam, pentazocine, and nitrous oxide. The trachea of each patient was intubated with a saline-filled double-cuffed endotracheal tube. Changes in breathing pattern were measured with a pneumotachograph while changes in laryngeal wall tension and tracheal wall tension were assessed by measuring changes in the proximal cuff pressure and the distal cuff pressure, respectively. In 8 of 13 patients, the dose-response relationship for each anesthetic was determined by administering different concentrations (1, 3, and 5%) of gas mixtures. In these patients, nasal insufflation of 1 and 3% of each anesthetic did not produce any reflex response, whereas reflex responses were evident during nasal insufflation of 5% enflurane, isoflurane, and halothane. In all 13 patients, nasal insufflation of all three anesthetics at a concentration of 5% invariably produced changes in breathing pattern characterized by prolongation of expiratory time (TE). However, prolongation of TE was the most pronounced for enflurane (from a control value of 2.1 +/- 0.5 to a maximum value of 4.8 +/- 2.2 s [mean +/- standard deviation]), less for isoflurane (from 2.2 +/- 0.5 to 3.9 +/ 1.7 s), and the least for halothane (from 2.2 +/- 0.6 to 2.9 +/- 0.9 s).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1888051 TI - Measurement of pulmonary blood flow with transesophageal two-dimensional and Doppler echocardiography. AB - Transesophageal echocardiography permits measurement of the pulmonary artery diameter (two-dimensional echocardiography) and pulmonary artery blood flow velocity (pulsed-wave Doppler). These measurements considered with the heart rate allow for the determination of pulmonary artery blood flow, which is equivalent to cardiac output. This study compared the precision of transesophageal Doppler derived cardiac output (DdCO) with the precision of thermodilution cardiac output (TdCO) and examined the agreement between DdCO and TdCO in 33 cardiac surgical patients. The proximal pulmonary artery diameter was measured in triplicate during systole and end expiration, and the local blood flow velocity was recorded on video tape. The instantaneous pulmonary artery blood flow velocity (centimeters per second) for three random cardiac beats was integrated with respect to time. DdCO was calculated as the product of the flow velocity integral (centimeters per beat), heart rate (beats per min), and the mean cross-sectional area (centimeters squared) of the main pulmonary artery. At the same time that the velocity recordings were made, three serial determinations of TdCO were made by an independent observer. Pulmonary blood flow could be measured in 25 of the 33 patients. The anatomical relationship among the esophagus, the left main stem bronchus, and the pulmonary artery did not allow adequate imaging of the pulmonary artery in 8 (24%) of the patients. A total of 45 sets of triplicate measurements were made. The range of cardiac outputs encountered was 1.7-6.6 l.min-1 by TdCO and 1.5-6.9 l.min-1 by DdCO. The 95% confidence limits for the difference between the two methods (agreement) was 0.030 +/- 0.987 l.min 1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1888052 TI - Postoperative epidural morphine is safe on surgical wards. AB - The use of epidural morphine for postoperative analgesia outside of intensive care units remains controversial. In this report our anesthesiology-based acute pain service documents experience with 1,106 consecutive postoperative patients treated with epidural morphine on regular surgical wards. This experience involved 4,343 total patient days of care and 11,089 individual epidural morphine injections. On a 0-10 verbal analog scale, patient-reported median pain scores at rest and with coughing or ambulation were 1 (inter-quartile range 3) and 4 (interquartile range 4), respectively. The incidence of side effects requiring medication were as follows: pruritus 24%, nausea 29%, and respiratory depression 0.2%. There were no deaths, neurologic injuries, or infections associated with the technique. Migration of epidural catheters into the subarachnoid space and into epidural veins each occurred twice. Overall, 1,051 of the 1,106 patients (95%) experienced none of the following problems: catheter obstruction, premature dislodgement, painful injections, catheter migration, infection, or respiratory depression. We conclude that postoperative pain can be safely and effectively treated with epidural morphine on surgical wards. PMID- 1888053 TI - Right- and left-arm blood pressure discrepancies in vascular surgery patients. AB - To identify a relationship between atherosclerotic vascular disease and differences in blood pressure between the right and left arms, blood pressure differences between arms were measured in patients with peripheral vascular disease (PVD, n = 58), in patients with coronary artery disease (CAD, n = 38), and in patients with no evidence of atherosclerotic disease, who served as a control group (n = 38). The incidence and magnitude of right and left arm pressure difference determined by the oscillometric technique were compared between the patient groups. The incidence of systolic pressure difference greater than or equal to 20 mmHg between arms in patients with PVD (21%) was greater than that in either those with CAD (3%) (P less than or equal to 0.05) or control subjects (0%) (P less than 0.01). The incidence of systolic pressure difference greater than or equal to 45 mmHg between arms in patients with PVD (10%) was greater than that in either those with CAD (0%) (P less than 0.05) or control subjects (0%) (P less than 0.05). Patients with PVD also had a greater incidence of right and left arm difference than did those with CAD or controls for mean and diastolic blood pressures. Of all patients with a systolic difference greater than 10 mmHg, neither the right nor the left arm blood pressure was consistently higher: 21 of 35 (60%) had a higher pressure in the right arm, and 14 of 35 (40%) had a higher pressure in the left arm (P = 0.33). Gender, diabetes, hypertension, smoking, and age were not associated with a difference in blood pressure between the right and left arms.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1888054 TI - Altered load dependence of postischemic myocardium. AB - Intermittent myocardial ischemia can produce areas of postischemic ("stunned") myocardium in the heart of the human with coronary artery disease. These areas are no longer ischemic, but have diminished contractile performance. Although the effects of loading conditions on systolic contraction of normal, ischemic, and failing myocardium have been investigated in great detail, the way in which load affects contraction of postischemic myocardium is not known. The aim of this study was to determine in anesthetized dogs how loading conditions affect the systolic function of a region of myocardium after 10 min of ischemia and 1 h of reperfusion. Sets of piezoelectric crystals were implanted in a test zone and in a remote zone of myocardium. Measurements of systolic wall thickening were made during nine combinations of left atrial pressure (3, 6, and 9 cmH2O) and mean arterial pressure (70, 90, and 110 mmHg). One set of measurements was made under baseline conditions, and a second set was made after 10 min of coronary occlusion and 1 h of reperfusion. Ischemia and reperfusion reduced wall thickening in the test zone 36 +/- 3% and diminished the response to increases in preload. In contrast, the response of the test zone to changes in afterload was unchanged. An interaction between the test zone (in which depressed contraction was observed) and the surrounding myocardium (in which enhanced function was observed) produced the appearance of a regional wall motion abnormality as afterload increased. These results emphasize that the load dependence of postischemic myocardium differs from that of normal myocardium and must be taken into account in clinical studies in which regional contraction is used to monitor the heart for ischemia. PMID- 1888055 TI - A thromboxane analog increases pulmonary capillary pressure but not permeability in the perfused rabbit lung. AB - Thromboxane has been implicated as a mediator of pulmonary hypertension and pulmonary edema in acute respiratory failure. Pulmonary edema may result from increased pulmonary capillary hydrostatic pressure or from increased pulmonary vascular permeability. We therefore studied the effects of a stable thromboxane analog, U46619, on these two parameters in the perfused rabbit lung. Pulmonary capillary pressure was measured by the double vascular occlusion method, and pulmonary vascular permeability was estimated by measurement of the pulmonary fluid filtration coefficient (Kf). U46619 infusion produced pulmonary hypertension and lung weight gain; increased both the arterial (precapillary) and venous (postcapillary) components of pulmonary vascular resistance; and increased pulmonary capillary pressure from 4.7 +/- 0.5 to 9.0 +/- 0.7 mmHg (P less than 0.01). The isogravimetric pressure (equivalent to the capillary pressure corresponding to no lung weight gain) was 4.0 +/- 0.4 mmHg before U46619 and 4.6 +/- 0.4 mmHg during U46619. Therefore, U46619 significantly increased capillary pressure above isogravimetric pressure and resulted in the development of pulmonary edema. U46619 did not affect vascular permeability as measured by Kf. We conclude that pulmonary venoconstriction resulting in increased pulmonary capillary hydrostatic pressure is the major mechanism by which thromboxane produces pulmonary edema in isolated lungs. PMID- 1888056 TI - Effects of anesthesia on norepinephrine kinetics. Comparison of propofol and halothane anesthesia in dogs. AB - Alteration of sympathetic function is a major determinant of the cardiovascular effects of anesthetic agents. Plasma norepinephrine (NE) concentrations are determined not only by the rate of NE release from sympathetic nerves but also by NE clearance rate. Therefore, NE concentration in plasma may be an inadequate index of sympathetic activity. We used an isotope dilution technique to investigate the effects of halothane and propofol anesthesia on NE kinetics. A relationship of NE kinetics to halothane dose was determined in six dogs. Halothane 1.0 MAC reduced plasma NE concentration by 35 +/- 9% versus awake (P less than 0.05). This was due to a reduction of 52 +/- 9% in NE spillover (P less than 0.05) accompanied by a reduction of 27 +/- 5% in NE clearance (P less than 0.005). The clearance changes were dose-dependent: reductions were 34 +/- 4% at 1.5 MAC (P less than 0.05 vs. 1.0 MAC) and 45 +/- 5% at 2.0 MAC (P less than 0.05 vs. 1.5 MAC). Six dogs were studied with a single halothane dose (1.0 MAC) and NE concentration, spillover, and clearance were found to be stable over a period of 5.5 h of anesthesia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1888057 TI - Depression of baroreflex control of heart rate by halothane in growing piglets. AB - The purpose this study was to examine the effects of halothane on baroreflex control of heart rate in developing swine. Serial tests of baroreflex function were performed over the first 2 months of life in eight piglets in the conscious state and during anesthesia with 0.45, 0.9, and 1.35% halothane. Systemic blood pressure was increased with phenylephrine (pressor test) and decreased with nitroprusside (depressor test), and stimulus-response curves relating mean blood pressure to heart rate were constructed. Baroreflex sensitivity was determined as the slope of the linear portion of the curve. Halothane markedly depressed baroreflex sensitivity at all ages in a dose-dependent manner (conscious greater than 0.45% greater than 0.9%, 1.35%). Increasing age was accompanied by decreasing baroreflex sensitivity in both the conscious and the anesthetized states. The difference in baroreflex sensitivity between conscious and anesthetized states did not change with age for the depressor test (tachycardia response), but it did change with age for the pressor test (bradycardia response). For this test, conscious values converged toward anesthetized values at higher ages; therefore, there was relatively less depression by halothane at older ages. Halothane also decreased resting heart rate and decreased the limits and narrowed the range of the baroreflex heart rate response. Increasing age was accompanied by a decreasing resting heart rate and by decreasing limits and a narrowing range of the baroreflex response. The effect of halothane on heart rate variables was similar at all ages. Halothane decreased resting blood pressure and decreased the lower limit and widened the span of the baroreflex blood pressure range.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1888059 TI - Quadriplegia in a patient with cervical spondylosis after thoracolumbar surgery in the prone position. PMID- 1888058 TI - Malignant hyperthermia: normal muscle calcium uptake and abnormal caffeine and halothane contractures. PMID- 1888060 TI - Life-threatening hypoxemia after lithotripsy in an adult due to shock-wave induced pulmonary contusion. PMID- 1888061 TI - Spontaneous ventilation via transtracheal large-bore intravenous catheters is possible. PMID- 1888062 TI - Therapeutic suppression of a permanent ventricular pacemaker using a peripheral nerve stimulator. PMID- 1888063 TI - Cardiopulmonary bypass in a patient with factor XII deficiency. PMID- 1888064 TI - Epidural opioid analgesia does not obscure diagnosis of compartment syndrome resulting from prolonged lithotomy position. PMID- 1888066 TI - Ethics in publication and the "operator". PMID- 1888065 TI - Treatment of cocaine-induced cardiovascular toxicity. PMID- 1888067 TI - Tracheal extubation in children. PMID- 1888068 TI - Truth in advertising: the journal's responsibility. PMID- 1888069 TI - A new presentation of post-dural puncture complication. PMID- 1888070 TI - Aids for fiberoptically guided intubation in children. PMID- 1888071 TI - Induction dose of propofol in infants and children. PMID- 1888072 TI - [Morphometric analysis of an Anoplocephala perfoliata population]. AB - An Anoplocephala perfoliata population isolated from the caecum of a dead horse was analysed morphometrically. Besides the number of segments, length and width of strobila, the width of scolex and the last segment, in adult tapeworms the number of eggs per segment was counted. By the aid of these data the population was divided into 4 categories. The length of fixed tapeworms varied between 5.46 and 41.53 mm. There was an direct relation between length of the strobila and number of segments. Only 42 of 440 investigated tapeworms contained mature eggs in the uterus. The number of eggs varied between 125 and 4482. The beetle mite Scheloribates latipes could be infected successfully, 9 cysticercoids were isolated from their body cavity. PMID- 1888073 TI - [Sphaerospora truttae (Myxosporidia) in Salmo trutta and Thymallus thymallus: first detection in Thuringia and in the Hartz region and also in the grayling]. AB - S. truttae is described from brown trout and grayling in Middle Germany. This species is obviously not connected with PKX, the causative agent of Proliferative Kidney Disease (PKD) in salmonids. S. truttae, however, is important in this connection from the viewpoint of differential diagnostics. PMID- 1888074 TI - [Determination of the purity of Eimeria species of chickens]. AB - The morphologic criteria length and breadth were used for the examination of the purity from 23 strains of different Eimeria species in the fowl (Eimeria tenella, E. acervulina, E. maxima, E. necatrix) by three methods: Tabulate graphic method, determination of the size of concentration, analysis with counter. The tabulate graphic method by use of peak value as only criterion of valuation has suitable proved for the screening test. A qualification of the degree of purity is reached in the form of classes of homogeneity with the criteria peak value, first and second classes of the neighbour by the determination of the size of concentration. The quantitative certainly of the assertion increases by the analysis with counter from six statistical parameters (frequency of peak value, frequency of the sum from peak value, first and second classes of the neighbour, number of taking classes in the specific range of species, coefficient of variation, coefficient of correlation, divergence of specific index of the form in the species). PMID- 1888075 TI - [A titrographic method for determining the glycolysis flow rate with Plasmodium berghei-infected red blood cells]. AB - A procedure is described for the elucidation of the glycolytic flux rate of red blood cells infected with the malarial parasite Plasmodium berghei. It is based on the titration of the protons originating from the glycolytic lactate accumulation. Compared with traditional methods of biochemical measurements of glucose consumption or accumulation of lactate the proposed procedure shows the following advantages: continuously measurement is possible; constancy of the pH value during the measurement; lower amounts of biological material are necessary (increased sensitivity) increased accuracy; The method can also be applied to studies on other cells and species with normal or increased glycolytic flux rate. PMID- 1888076 TI - [Experimental animal studies for the detection of circulating Toxoplasma antigens]. AB - Rabbits and mice were infected by Toxoplasma gondii (RH and HanR) and Hammondia hammondi. An enzyme immunoassay with monoclonal antibodies was used to reveal circulating Toxoplasma antigens. They were found only in mice and rabbits that had been infected by the cyst-forming strain Toxoplasma HanR. In mice infected by Hammondia hammondi low antibodies titres were found that showed a cross-reaction with Toxoplasma. The enzyme immunoassay for evidence of Toxoplasma antigens demonstrated a negative reaction in these animals. PMID- 1888078 TI - ANA is nurse's workplace partner. PMID- 1888077 TI - Comparative study of clinical signs, haematology and prevalence of trypanosomiasis in Holstein Friesian and White Fulani Zebu cattle exposed to natural infection in a rain forest zone of Nigeria. AB - A comparison of the symptomatology, haematology and prevalence of trypanosomiasis in Holstein Friesian and White Zebu cattle exposed to natural infections on a ranch in a rain forest zone of Nigeria is presented. 23 (44%) of the adult Friesians had trypanosome infections with a generally heavy parasitaemia. Infection was light in the Friesian calves and the Zebus with infection rates of 2 (6.9%) and 3 (15%) respectively. Trypanosoma vivax was the sole species encountered on the farm. There was a general unthrifty appearance in the adult Friesian herd as well as classical signs of trypanosomiasis. The Friesian calves and Zebus were generally in good conditions with an appearance of good health except one each of the infected animals which showed apparent symptoms of the disease. There was a marked reduction of the red cell values of the infected adult Friesian and Zebu cattle. The red cell values of the uninfected adult Friesians were equally depressed suggesting cryptic infections or that they were cured parasitologically by the recently administered trypanocide. The Friesian calves had normal red cell values for both the infected and uninfected. Leucocyte counts were generally high on the Farm and higher for the infected animals. PMID- 1888079 TI - Burn care nurse is special breed. PMID- 1888080 TI - Waste policy is health issue. PMID- 1888081 TI - ANA pushes feds on hazards to nurses. PMID- 1888082 TI - Proposed plan would halt encroachment by assistants. PMID- 1888083 TI - RNs oppose mandatory HIV testing. Quality patient care tops list of what's important to nurses. PMID- 1888084 TI - ANA mounts effort to immunize urban, rural children. PMID- 1888085 TI - Worker safety must be priority. PMID- 1888086 TI - Working conditions present risks. PMID- 1888087 TI - Vision and personal regard for members. PMID- 1888089 TI - Higgerson to JCAHO committee. PMID- 1888088 TI - Did DCAHO abolish care plans! Yes! As I see it. PMID- 1888090 TI - AIDS legislation sent to House. PMID- 1888092 TI - Physician payment: why it matters to nurses. PMID- 1888091 TI - Senate votes penalties for health care workers. PMID- 1888093 TI - Risk estimates for carcinogenic effects of radiation. PMID- 1888094 TI - The relative contributions of different organ sites to the total cancer mortality associated with low-dose radiation exposure. PMID- 1888095 TI - Low-dose radiation epidemiological studies: an assessment of methodological problems. PMID- 1888096 TI - Genetic effects of ionising radiation in man. PMID- 1888097 TI - Ionising radiation and the developing human brain. PMID- 1888098 TI - Kinetics of particle retention in the human respiratory tract. AB - A mathematical model of retention of insoluble aerosol particles penetrating the lungs during inhalation has been described. Based on data of the streams of deposited particles and their residence times in the subsequent generations of bronchial tree the retention dynamics of particles with diameters 5, 1 and 0.01 microns in the air-spaces has been determined. PMID- 1888099 TI - Strategy of analysis and interpretation of thermal working conditions. AB - This paper proposes a strategy for the management of heat problems at the workplace. This includes three steps of analysis: the first aims at recognizing the problem and classifying it under one of the categories--comfort, discomfort but no health risk, or health risk either in the long term or in the short term. The second is designed to evaluate the magnitude of the problem and to optimize the choice of solutions. The interpretation of the data is based on analytical indices: the PMV-PPD indices for heat discomfort conditions and the Required Sweat Rate index for heat stress conditions. The third step involves an in-depth analysis of the situation: this will be undertaken only if a major problem of heat stress has been detected at the previous stage and providing technical solutions cannot be immediately implemented. The advantages and possible limitations of this step-by-step approach are outlined and its cost effectiveness is discussed in the perspective of a true management of health and safety at work. PMID- 1888100 TI - Exposure to vibration and self-reported health complaints of riveters in the aircraft industry. AB - Workers using vibrating tools may experience neurological and vascular symptoms in the fingers and hands. The effect of vibration exposure on bone and joint disorders in the hand, arm and shoulder is less clear. In a cross-sectional study, riveters and controls in an aircraft company were investigated for vibration exposure and health complaints. Vibration measurements showed that frequency-weighted acceleration levels for riveting hammers and bucking bars ranged from 5.5 to 12.3 m s -2. The calculated equivalent frequency-weighted acceleration for a period of 4 h was the questionnaire survey 101 riveters reported statistically significant more complaints of pain and stiffness in their hands and arms when compared with 76 controls with no, or little, exposure to vibration. After 10 years of exposure statistically significant age-adjusted odds ratios (P less than 0.05) were found for vibration-induced white finger (VWF) (1.9) and pain or stiffness of the wrist (3.2). Although they were not statistically significant (0.05 less than P less than 0.10) odds ratios appreciably greater than 1 were found for numbness in fingers (1.6) and pain or stiffness in the elbow (1.6) and the shoulder (1.5), and these complaints were strongly associated with duration of exposure to vibration. With logistic regression the probabilities for a riveter of having symptoms of VWF after 10 and 20 years of exposure was estimated to be P = 0.18 and P = 0.29, respectively, which can be compared with the prevalences predicted by the dose-response relationship for VWF in ISO 5349, which are 10 and 30%. The results of this study suggest that exposure to vibration from working with impact power tools can contribute to complaints of pain and stiffness in the hand, arm and shoulder, and especially in the wrist. PMID- 1888101 TI - Long-term effects of soldering fumes upon respiratory symptoms and pulmonary function. AB - To evaluate the long-term effect of soldering gases and fumes, and of cigarette smoke on lung function, and the prevalence of respiratory symptoms, a comparative study of spirometric measurements in 57 solderers engaged in acetylene gas soldering of brassware joints in the brass industry (mean exposure: 12.4 +/- 1.1 years) and in 131 controls was performed. The two groups were similar in age, height, smoking habits and social class. The prevalence of respiratory symptoms in the solderers did not differ significantly from that in the unexposed controls (59.6 vs 56.4%). However, solderers who smoked showed higher prevalence of respiratory symptoms than those who did not smoke; a similar trend was observed in the controls. The study failed to demonstrate any association between the respiratory symptoms and length of exposure. The respiratory status of the solderers was unaffected as the results of spirometric measurements of lung function did not show any significant differences between the exposed and the control groups, indicating the absence of an additive effect of cigarette smoking and exposure to soldering fumes. PMID- 1888102 TI - Physiological modelling of organic compounds. AB - In pharmacokinetic modelling the body is represented as a set of compartments. The characteristics of these compartments are defined either by fitting predetermined mathematical equations to the data ('data-based compartments') or by defining compartments based on the actual biological structure of the animal ('physiologically based compartments'). Physiological models of chemical disposition are developed using these physiologically based compartments. These models then consist of sets of organs or types of tissue compartments whose characteristics are based as far as possible on the anatomy and physiology of the test species. Individual organs or types of tissue are defined with respect to their blood flow, volume, kinetic constants for metabolism, storage capacity for the compound involved, protein binding and other relevant characteristics. Linking these compartments together in a proper anatomical arrangement yields the physiological model for compound disposition. This paper provides an overview of the basics for constructing physiological models for organic compounds, focusing on the structure of individual compartments in these models and the data required for model development. Some past applications of physiological models are reviewed and speculation offered on future developments in this field. PMID- 1888103 TI - Modelling of respiratory exchange of polar solvents. AB - Physiologically based pharmacokinetic (pbpk) models are frequently used to describe the kinetics of inhaled gases and vapours. In these models the conducting airways of the respiratory tract are generally assumed to act as inert tubes. The function of the inert tubes is merely to conduct the vapour to the alveolar regions where the actual exchange between ambient air and body takes place. Such an 'inert tube' model may be adequate to describe the inhalation and exhalation kinetics of inert vapours, for example non-polar solvents which have a low water solubility. Experimental data suggest, however, that the 'inert tube' model may be erroneous for polar solvents which have a high water solubility. To explore this possibility further a tentative pbpk model was developed. Model structure and parameters were obtained from the literature on lung anatomy and physiology and by visual fitting to experimental acetone, carbon dioxide, diethyl ether and ethanol data. The model was written and solved by spreadsheet programming on a personal computer. Simulations were carried out to illustrate the difference between end-exhaled and alveolar air and how water solubility and workload influence the uptake and excretion kinetics of polar solvents. It is concluded that the model is valuable for predicting the lung kinetics of polar vapours under various circumstances. It may therefore be useful in the development of biological monitoring methods based on breath sampling and help us to understand and to explain experimental data. PMID- 1888104 TI - A case report of contaminated operating theatre multipurpose equipment: a potential hazard for health care workers. AB - The problem of bacterial contamination of clinical and operating equipment is well recognized [Claymane et al., J. Cataract Refract. Surg. 12, 158-161 (1986); Magnusson et al., J. Hosp. Infect. 7, 86-90 (1986)] and appropriate methods are available for ensuring adequate cleanliness. Operating theatre equipment may contain complex electro-mechanical technology which requires substantial 'down time' for maintenance and cleaning. Often this is not built into operating theatre schedules and problems can occur. Opportunistic bacteria may colonize surfaces in semisealed parts of equipment where, since these areas are not normally subject to cleaning procedures, their growth may go undetected. This could have serious clinical consequences. While the risk to patients is obvious [Bengtsson et al., J. Hyg., Camb. 83, 41-57 (1979)] theatre and maintenance staff may also be at risk, particularly if they have well controlled chronic disease which could predispose them to opportunistic infection. We describe bacterial contamination in the pump unit and exhaust of a combined electrosurgical/suction/fibre light unit commonly used in operating theatres throughout the U.K. A method of ensuring acceptable freedom from bacterial contamination is discussed. PMID- 1888106 TI - Occupational Hygiene Standards Committee of the British Occupational Hygiene Society and the Institute of Occupational Hygienists. PMID- 1888105 TI - An investigation of environmental impact on health of workers at retail petrol pumps. AB - Ninety-four male pump workers, employed in 41 petrol filling stations in Kanpur (formerly Cawnpore) and Lucknow--both in the Ganges plain of north India--were clinically examined. Headache, redness in eyes, lacrimation and signs like coated and/or furred tongue, throat and/or conjunctival congestion and carious teeth were significantly higher (P less than 0.05) in workers exposed to petrol fumes than in controls, as also was the level of phenol in urine (P less than 0.01). Environmental measurements revealed higher concentrations of benzene, sulphur dioxide and photoionizable dust in the air at petrol stations, and most of the symptoms and signs could be attributed to petrol fumes and other environmental pollution. PMID- 1888107 TI - Sphincter-saving surgery for rectal carcinoma. Comparison of two five-year periods from 1980 to 1989. AB - The early results of treatment for rectal adenocarcinoma in 290 patients were compared in two five-year periods, from 1980 to 1989, considering sphincter preservation. Altogether, 223 patients (77%) had radical surgery and the primary tumour was excised in 267 cases (92%). Operative mortality was 2.8% (8 patients), 3.2% in the first and 2.3% in the second five-year period. Sphincter-saving surgery was undertaken in 68 of 157 patients (43%) and in 90 of 133 patients (68%) within the two periods. This failed in one (1.5%) and five (5.6%) patients (P greater than 0.05), respectively. Anastomotic leak rates were 1.4, 18 and 38% after anterior resections for tumours of the upper, middle and lower thirds of the rectum. Both mortality (1.4 vs 3.8%) and the total number of complications (23 vs 39%) were less after anterior resection than after abdominoperineal excision of the rectum. In conclusion, increased use of low anterior resection for rectal carcinoma has not led to higher mortality or overall morbidity, but the high leak rate after very low anastomoses remains to be solved. PMID- 1888108 TI - Can acid secretion be predicted in the duodenal ulcer patient by interpretation of mucosal biopsies? AB - At gastroscopy 4 biopsies were taken from the oxyntic mucosa in 51 patients with duodenal ulcer. The patients underwent an acid stimulating test by injecting 6 microgram 5-gastrin/kg bodyweight. The parietal cell density in the mucosa of the biopsies was determined by cell counting in a standardized lattice. The method was fully acceptable compared with morphometric analysis of the parietal cell density per volume, and had a low intra- and inter-observer variation. Parietal cell density showed a significantly positive correlation with peak acid output (PAO) in patients with PAO less than or equal to 25 meqH+/h, whereas a correlation not could be demonstrated in patients with PAO greater than 25 meqH+/h. The lack of correlation in patients with high acid secretion reduces the value of the parietal cell counting method in predicting acid secretion in patients with duodenal ulcer disease. PMID- 1888109 TI - Surgery of acute peptic ulcer haemorrhage. AB - During the years 1973-1985, 145 patients with acute peptic ulcer haemorrhage were treated surgically at the Department of Surgery, Turku University Central Hospital. The bleeding site was gastric ulcer in 76 patients; 58 of these were treated by gastric resection and 17 by ulcer excision combined with vagotomy and pyloroplasty. Forty-two out of 69 patients with bleeding duodenal ulcer were treated with partial gastrectomy, the remaining with transfixion and vagotomy and pyloroplasty. The rebleeding rate was 2% and reoperation rate 9% among the patients who had a resection. In contrast 19% of the transfixed and 12% of ulcer excision cases rebled. The primary overall mortality was 12%; 44% of the patients with recurrent bleeding died. Because rebleeding was the most important cause of mortality, partial gastrectomy in bleeding gastric as well as duodenal ulcer may be preferable. PMID- 1888110 TI - Multiple adenomas and synchronous hyperplastic polyps as predictors of metachronous colorectal adenomas. AB - The development of metachronous adenomas was evaluated in 56 patients, 34 men and 22 women, with a history of 139 removed adenomas and non-neoplastic polyps, in order to determine whether the presence of concomitant adenomas and hyperplastic polyps at the initial examination could predict a higher risk of new adenomas. Sixteen of the 56 patients developed 21 metachronous adenomas and 1 rectal carcinoma after a median follow-up of 2.8 years. Among the 16 patients developing metachronous adenomas there were significantly more men (P less than 0.01), patients with multiple adenomas (P less than 0.05) or patients with adenomas and synchronous hyperplastic polyps at the initial examination (P = 0.043) than among the 40 patients without new adenomas. The combination of multiple adenomas with synchronous hyperplastic polyps at the initial examination predicted best the risk of developing new adenomas (P = 0.005). The results of the study suggest that patients with multiple adenomas and synchronous hyperplastic polyps at the initial examination may comprise a new higher risk group for developing metachronous colorectal adenomas. PMID- 1888111 TI - Predictive factors of functional ability after lower-limb amputation. AB - Functional ability and accommodation situation were studied by personal interview and examination of 125 surviving lower-limb amputees after one postoperative year. Among ten independent variables studied by multiple linear regression analysis, an unfavourable association was found between increasing age and the following aspects of physical function: walking distance (P less than 0.001), walking time (P less than 0.001), amount of outdoor walking outdoors (P less than 0.001), increased need for aids to ambulation (P less than 0.01), use of a prosthesis (P less than 0.05). Using a partial correlation coefficient analysis of functional ability and accommodation situation, with adjustment for age, the time lag between surgery and prosthetic fitting, and the occurrence of cerebrovascular disease displayed a similar unfavourable association with prosthetic usage. In the group of BK (below-knee) amputees the length of the stump had a significant favourable relationship with walking distance (P less than 0.01). In the male group of vascular BK amputees, smoking had an unfavourable association with walking distance (P less than 0.01), ability to walk outdoors (P less than 0.01) and walking time (P less than 0.05). None of the variables showed any significant relationship with the postoperative accommodation situation. PMID- 1888112 TI - Results of the management of ureteric stones with the ureterorenoscope. AB - Eighty ureterorenoscopies (URS) were performed for stone removal in 67 patients between January 1985 and April 1988. The success rates for stone removal were 54% in the lower third of the ureter, 70% in the middle third, 38% in the upper third, and 33% in the renal pelvis. The overall success rate was 42%. Open ureterolithotomy was performed after failed ureteroscopy nine times. There were two perforations of the ureter: one by the hook of the forceps and the other by the dormia basket. No significant late complications occurred in 51 patients after six to 36 months postoperatively. At the moment ureteroscopy is of value particularly in the treatment of lower or middle ureteric stones. PMID- 1888113 TI - Painful spine after stable fractures of the thoracic and lumbar spine. What benefit from the use of extension brace? AB - In a series of 126 patients with conservatively treated stable fractures of the thoracic and lumbar spine, the fracture occurred most often (56%) in the thoracolumbar junction. The mean follow-up time was 7.2 years (range 5.5-10.7) and the mean age was 45.9 years (range 14-83). The radiological measurement of vertebral deformity and evaluation of clinical outcome showed that the patients with poor outcome had significantly greater anterior wall compression and kyphosis on admission than the patients with good outcome, but the deformity worsened similarly in both groups. The use of extension brace seemed to decrease subjective symptoms during the mobilization phase but it could not prevent the development of kyphosis deformity during the follow-up period. The results favour the conception of more effective treatment concerning patients with kyphosis of greater than or equal to 13 degrees or anterior wall compression of greater than or equal to 30% on admission, respectively. PMID- 1888114 TI - The angle-measuring device, a practical resource in high tibial osteotomy. AB - Thirty-two patients with medial gonarthrosis were subjected to high tibial osteotomy. In 16 knees the base of the osteotomy wedge was measured in mm using a caliper and in another 16 knees the angle-measuring device was used. The miscorrection in correlation to the aimed angle was in the first case 0.2 +/- 4.7 degrees, and in the second case 2.4 +/- 4.1 degrees varus undercorrection. The possible sources of error according to measurement of mechanical axis deviation angle of the knee, angle-measuring device and wedge measuring technique during surgery as well as laxity of knee and age-correlated need of overcorrection are pointed out. The angle-measuring device is an important tool especially in high tibial osteotomy of the knee. PMID- 1888115 TI - Surgical treatment of hydatidosis. AB - Hydatidosis is particularly widespread in some geographic areas. Among these Sardinia presents one of the highest incidences. The authors examine the results obtained of 382 patients submitted to surgery between 1973 and 1989. The average age was 38.9 years. Liver involvement was observed in 215 cases, lung involvement in 167 cases, while localizations in other organs were rare. Forty liver cysts and 54 lung cysts were complicated preoperatively. The patients were submitted predominantly to total or subtotal cysto-pericystectomy (270 cases), parenchymal resection (75 cases), simple cystectomy (40 cases). Total postoperative mortality was 2.35%. Postoperative time was significantly shorter after cysto pericystectomy and after parenchymal resection than after simple cystectomy. Patients suffering from multiple or complicated cysts were given supplementary chemotherapy. PMID- 1888116 TI - Diagnosis and treatment of ovarian cysts in children. AB - Seventeen girls were treated following the diagnosis of ovarian cysts. Four patients were operated on within the first 6 months of age and the other 13 patients were 10-15 years old at the time of diagnosis. Antenatal diagnosis was made in 3 cases. The presenting symptoms in the infants were distended abdomen in 3 cases, abdominal pain in 1 and vomiting in 1. In the older children the presenting symptoms were abdominal pain in 12, vomiting in 5 and elevated temperature in 6. Preoperative ultrasound was performed in 5 patients, 3 neonates and 2 older children. Sixteen of the 17 girls were operated on. The indication for surgery was an ovarian cyst with complication in the infants and in the older children the suspicion of acute appendicitis. The operative procedure was cyst uncapping in 7 cases, salpingo-oophorectomy in 4, ovarian resection in 2, ovarian fixation only in 1 and no ovarian intervention in 2. Asymptomatic infants with an ovarian cyst less than 4 cm in diameter can be managed conservatively. Surgery can be recommended after documented change of the cyst on ultrasound, large cysts giving rise to symptoms or presentation of an acute abdomen. Salvage of variable ovarian tissue is desirable. PMID- 1888117 TI - Venous gangrene of the limb. Pathophysiological and therapeutic considerations. AB - Venous gangrene of the limb is a rare disease. Peripheral arterial collapse has been shown to underlie the ischaemia. The two patients studied had venous gangrene and malignancy of the gastrointestinal tract with liver metastases. One patient had slowly and the other rapidly progressing gangrene despite heparin warfarin therapy. Both patients died. Microscopy revealed occlusive thrombosis of small peripheral arteries of the leg. The authors conclude that the pathophysiology in venous gangrene may be occlusive thrombosis of small arteries. This situation is the lethal form of the entity and responds poorly to established therapy. PMID- 1888118 TI - Oxygen tension and tissue perfusion. PMID- 1888119 TI - Birth fractures of long bones. AB - A case of traumatic separation of the proximal humeral epiphysis in a newborn is described. Three other cases of birth fractures of long bones have been taken care of in our hospital during 1980-89, when the frequency of birth fractures of long bones was 0.02%. The causes and diagnostic problems of these fractures are discussed. PMID- 1888120 TI - Continuous direct tissue oxygen tension measurement. A new application for an intravascular oxygen sensor. AB - An oxygen tension measurement equipment, developed for continuous intravascular monitoring was tested as a direct tissue oxygen tension meter. The sterile disposable oxygen probe consists of a Clark type polaro-graphic bipolar electrode placed in a 5 cm long flexible polyethylene catheter (OD 0.55 mm). The probe is easily placed, e.g. in subcutaneous tissue or muscle, with the aid of an introduction needle. In vitro measurements as well as subcutaneous and intramuscular readings were performed. The animals were subjected to various experimental conditions such as different inspiratory oxygen fractions, hypovolemia, and circulatory impairment. Results were comparable to those obtained with previously used and well characterized tissue oxygen tension measurement equipment. The clinical applicability of the oxygen sensor for tissue oxygen measurement was assessed in one patient by 40 hours' surveillance in a free myocutaneous flap. The procedure was simple and implied minimal discomfort for the patient. PMID- 1888121 TI - Lipid intake and atherosclerosis. AB - The importance of diet in the prevention and treatment of atherosclerosis is well known. Among the different nutrients, lipids certainly have a primary role. Dietary cholesterol can influence the progression of atherosclerosis by increasing cholesterol levels or by modifying the composition of lipoproteins. Epidemiological and clinical studies have clearly demonstrated a relationship between the intake of saturated fatty acids and atherosclerosis. Among these fatty acids, stearic acid has the smallest effect on cholesterol levels. Until a few years ago it was though that monounsaturated fatty acids (MUFA) did not affect lipoprotein metabolism. However, very recently it has been shown that MUFA have the same hypocholesterolemic effect as polyunsaturated fatty acids; moreover they do not induce a decrease in high-density lipoprotein cholesterol. Therefore the overall metabolic effect of MUFA seems to be beneficial. PMID- 1888122 TI - Relationship between dietary cations and blood pressure. AB - The relationship between dietary cations and blood pressure is complex. Epidemiological evidence points to a significant independent positive relationship between dietary sodium and blood pressure. The same evidence favours the existence of a significant negative relationship between dietary potassium and blood pressure. On a molar basis 1 mmol of potassium is about 2.5 times more effective in lowering blood pressure than sodium is in raising it. The evidence concerning the effect of dietary calcium on blood pressure remains controversial. Intervention studies favour a blood-pressure-lowering effect, but serum and urinary calcium correlate positively with blood pressure. Dietary magnesium has probably a slight blood-pressure-lowering effect, but more data are needed in order to evaluate its importance. At the population level blood pressure is significantly related to the dietary intake of cations. PMID- 1888123 TI - Food patterns in the British isles. AB - Food supply statistics can show the general dietary pattern in European countries. However, their energy content is 50% or more above physiological needs, and because the wastage of each food will be different within a country as well as between countries, comparisons between their nutrient content and a country's mortality may be unreliable. The types and amounts of food brought into the home are closer to what people eat, and this paper describes the main dietary changes which have occurred in Britain at this level since 1970. During a time when life expectancy increased and mortality from coronary heart disease fell, the main characteristics of the diet remained British, but it became more pre packaged. Many recent changes were in the direction advocated by nutritionists, but, because of a decline in sugars and starches as well as in fat, the proportion of energy derived from fat remained at about 42%. Intakes of several other nutrients also declined, but the ratio of polyunsaturated to saturated fatty acids doubled to 0.37. PMID- 1888124 TI - Food patterns and health problems: central Europe. AB - Central Europe comprises a heterogeneous group of some 120 million persons from 11 countries which differ greatly in food availability and preferences. The region has undergone dramatic changes in food consumption patterns and in the patterns of nutritionally related diseases. The changes in the political situation in central Europe have provided a unique natural experiment which allows the study of the effects of different eating behaviors on health within a genetically homogeneous population and an analysis of the time frame in which effects can be seen at the national level. This is in particular the case for the FRG and the GDR. Epidemics of nutritionally related disease have arisen, including cardiovascular disease, cancers of the colon and breast and obesity. These occur at very different rates in neighboring countries. Furthermore, unknown factors, probably including food-hygienic factors and methods of storage and preparation, have resulted in drastic reductions in the rates of stomach cancers in all countries. These have only recently been detected, as no systematic nutritional surveillance systems are currently in effect in Europe. Due to the chronic nature of the diseases in question, we are noticing too little, too late. Food patterns provide a realistic and sensitive predictor of disease incidence. They are timely enough to detect changes before they are reflected in a diminished health status of the population or specific risk groups. Details on the patterns of intake and secular trends, as far as they are available for individual countries, reveal that eating behavior is quite labile and subject to dramatic changes within decades. The current information status does not allow a closer examination of specific population groups, such as the behavior of children or the elderly, the intakes of pregnant or breast-feeding women, or the eating behavior of men at high risk of heart disease. The foundations of a European nutrition surveillance system need to be laid, to make possible the timely detection of high-risk-related changes in food consumption, unfavorable trends and early signs of nutritionally related epidemics. The regular, standardized assessment of eating patterns will be an important building stone in such a system. PMID- 1888125 TI - Food patterns in the Nordic countries. AB - The purpose of the work reported is to provide a first-order assessment of food patterns and food pattern trends in each of the Nordic countries. The primary source of input has been food supply data for the period of 1970-1988. The study reveals that important changes in food consumption have taken place over the last 20 years. In Finland and Norway, this has resulted in a reduction of energy contribution from fat to 35%. For Denmark and Sweden no such reduction is observed. The data are intended for use in a wider context in a transeuropean search for relations between health problems and food patterns. PMID- 1888126 TI - Diet patterns and health problems: diet in southern Europe. AB - The diet of the populations in southern Europe, particularly those living in the Mediterranean areas, was characterized by a relatively higher consumption of fish, olive oil, vegetables and fruit and by a lower consumption of meat and animal fat. In terms of nutrients the most significant difference between the Mediterranean type of diet and the diet of continental and northern European populations was in the consumption of saturated and monounsaturated fatty acids and to a lesser degree in the intake of protein, sugar and alcohol, as well as in regard to the dietary fiber content. Since the Mediterranean populations have shown a lower total mortality rate as well as a specific mortality from coronary heart disease (CHD) which in part could be explained by their dietary habits, the Mediterranean diet has often been proposed as a prototype on which dietary measures for the prevention of CHD in populations should be developed. However, more recent data indicate that in the last 20 years the food pattern of the Mediterranean populations was subjected to substantial changes, particularly in regard to the increase in meat and dairy product consumption which in turn has resulted in an increase in the percentage of energy of saturated fats and which has also affected the ratio of monounsaturated to saturated fatty acids. These changes have also affected some of the risk factors of CHD in those populations. PMID- 1888127 TI - Health status in Finland and other Nordic countries with special reference to chronic non-communicable diseases. AB - It is a general belief that the health status of the populations of the Nordic Countries, Denmark, Finland, Iceland, Norway and Sweden is very good. Infant mortality is the lowest in these countries. However, other indicators of the health status such as overall life expectancy and incidence of mortality from chronic non-communicable diseases demonstrate a large variation between the Nordic countries. Compared with other countries frequency of several non communicable diseases is among the highest worldwide. Moreover, the incidence and mortality trends in non-communicable diseases suggest a heterogeneous development among the Nordic countries. PMID- 1888128 TI - Trends in mortality in Britain: 1920-1986. AB - In Britain continuing declines in infant mortality have ensured that life expectancy at birth has consistently improved during this century. Life expectancy in middle ages showed small declines between 1921 and 1940, probably due to real increases in coronary heart disease and cancer mortality which were not counterbalanced by falls in infectious disease mortality of sufficient magnitude. The persistence of social class differentials during this period and the role of diet are discussed. It is suggested that the reversal in the trend in overall mortality seen earlier this century in Britain has implications for recent mortality trends in Eastern Europe. PMID- 1888129 TI - Health in central Europe. AB - Some of the 11 central European countries enjoy today a high level of health, among the highest life expectancies worldwide and, concomitantly, low or intermediate risk factor levels for some of the major chronic diseases. However, on a regional level, and particularly according to social groups, important differences in risk, morbidity and mortality still remain. Perhaps the most dramatic differences now found relate to east-west differences within Europe. This paper addresses these issues drawing upon examples such as cancer of the colon and coronary heart disease. PMID- 1888130 TI - Food patterns and health problems: health in southern Europe. AB - The health status description refers to 7 countries of southern Europe, i.e. Portugal, Spain, France, Italy, Malta, Yugoslavia and Greece, and is mainly derived from official mortality data. In general the health status of southern European countries, as related to the adult population, seems satisfactory and improving along the last 10-15 years in spite of the adverse trends of some diseases. As compared to central, northern and eastern European countries, the southern ones enjoy relatively low mortality and morbidity rates from coronary heart disease and cardiovascular diseases in general, from lung cancer, from large bowel cancer and all-causes mortality, whereas they suffer from strokes and liver cirrhosis at relatively high rates. An exception is made by Yugoslavia where trends in death rates from cardiovascular diseases and all-causes mortality are definitely increasing like it has happened in eastern Europe during the last 20 years. Data from official mortality records are supported by information on incidence, mortality and risk factor distribution derived from population studies like the Seven Countries Study, the Erica and the Monica Project. PMID- 1888131 TI - Food patterns and health problems: conclusions of the chairman. PMID- 1888132 TI - Methodological considerations on intra- versus interpopulation correlation studies. AB - Epidemiological studies on the diet-health relationship have frequently resulted in confusing controversies rather than in clear and consistent findings. As an illustration of this phenomenon the relationship between dietary cholesterol and coronary heart disease (CHD) is used in this presentation. The epidemiological evidence favoring a strong and causal relationship between dietary cholesterol, serum lipids and CHD relied until some years ago largely on studies between populations. However these studies are more susceptible to confounding error. Therefore epidemiological studies have been conducted within populations looking into the relationship between dietary cholesterol, CHD risk and CHD frequency on the individual level. Until recently no consistent association had been observed between dietary cholesterol and serum total cholesterol levels or between dietary cholesterol and CHD mortality in homogeneous groups of individuals; this relates probably to methodological problems in measuring the dietary variable with sufficient precision. More recent studies using a more precise dietary methodology and a prospective study design over longer time periods result in observations that are more in line with the interpopulation study observations. Besides epidemiological evidence it is necessary to compare these findings with those from experimental work and from clinical studies. This approach has the best chance to separate ecological fallacy from real existing associations between diet and health. PMID- 1888133 TI - Diet and cancer: the role of case-control studies. AB - The advantages and disadvantages of case-control studies of the role of nutrition in cancer etiology are examined. The results, the scientific conclusions and the policy implications of several such studies undertaken in Athens are discussed. PMID- 1888134 TI - Long-term prospective studies: the only solution? AB - One of the advantages of prospective studies in nutritional epidemiology is that dietary patterns and nutrient intake data are collected before the occurrence of the disease. With such a design it is possible to study the contribution of dietary variables in explaining the occurrence of diseases between different cultures and within populations. In order to make a good estimate of the relation between a dietary variable and the occurrence of a disease in long-term prospective studies, it is necessary to have insight in the changes of dietary variables with time. For prospective cohort studies also information about the reproducibility of a dietary variable is needed. Long-term prospective studies with repeated dietary measures provide a powerful tool in studying diet-disease relations, but practical limitations may prevent the implementation of such designs. PMID- 1888135 TI - Dietary patterns and cancer. AB - The possible role of dietary habits in the aetiology of cancers, and in the differences observed in the prevalence of this group of diseases between populations, should be considered in the context of the competing theories of cancer causation. This paper briefly reviews the historical context in which the contemporary emphasis on nutritional influences in cancer causation is placed and outlines the scope of the evidence currently available. PMID- 1888136 TI - Metastatic T-cell hybridoma cells display target preference for invasion ('homing') in tissue culture models. AB - BW-O-Li1 murine T-lymphoma cells display target preference for invasion in two different in vitro models. In the precultured chick heart fragment (PHF) assay, BW-O-Li1 preferentially invaded into aggregates of MCF-7 mammary carcinoma cells rather than into PHFs. In a monolayer invasion assay (MIA), BW-O-Li1 cells preferentially invaded under 10 T1/2 mouse embryo cell monolayers rather than under MCF-7 monolayers. Thus, although BW-O-Li1 cells were perfectly able to invade into any of the targets presented, they migrated and accumulated preferentially in one of the targets when a choice was offered. We suggest that this in vitro 'homing' phenomenon can be exploited to investigate certain aspects of organ-specific metastasis. PMID- 1888137 TI - Induction of morphological transformation, anchorage-independent growth and plasminogen activators in non-tumorigenic human osteosarcoma cells by lead chromate. AB - The possible carcinogenicity of insoluble chromium (VI) compound, PbCrO4, in human cells has been tested using a nontumorigenic human osteosarcoma cell line (HOS, TE 85). Electron microscopic studies show that PbCrO4 is phagocytosed by HOS cells and accumulates within the vacuoles in the cytoplasm. A number of cell lines have been isolated following multiple treatment of HOS cells with PbCrO4. These cell lines are morphologically different from HOS cells, form anchorage independent colonies in soft agar and form quickly regressing small tumor nodules in athymic nude mice. The cellular and secreted plasminogen activator (PA) levels of 5 cell lines isolated after PbCrO4 treatment are increased up to 8 fold and up to 10 fold respectively as compared to untreated HOS controls. SDS-PAGE analysis in the presence of copolymerized substrates is consistent with increase in 55 kDa urokinase-type PA (u-PA) and 68 kDa tissue-type PA (t-PA). These results show that PbCrO4 treatment leads to stable phenotypic changes indicative of the transformation of HOS cells. PMID- 1888138 TI - Chromosome anomalies in human breast cancer: evidence for specific involvement of 1q region in lymphocyte cultures. AB - Constitutional chromosome abnormalities that may predispose a group of individuals to develop certain neoplasms have been reported for some human solid tumors. Deletions of 13q in retinoblastoma, 11p in Wilms' tumor, 1p in neuroblastoma, 3p in renal cell carcinoma, 5q in colorectal carcinoma and 22q in meningioma are examples of such anomalies. In breast carcinoma, a specific cytogenetic defect has not been conclusively identified. We have studied Phytohemagglutinin-stimulated lymphocytes of 76 breast cancer patients, 68 predisposed family members, 40 controls, and 30 additional controls with lung cancer to determine whether nonrandom chromosome defects are present. From each sample 100, G-or Q-banded metaphase spreads were studied for rearrangements. A marked clustering of alterations in the long arm of chromosome no. 1 (q11-22) was seen in breast cancer patients and in some predisposed family members. Alterations in 1q were present in 1% to 3% of metaphases, and included translocations to chromosomes 3, 6, 7, 9, 12, 15, 17, 18, 21 and the X; deletion of 1q, or pericentric inversion. Twelve out of 62 (19.3%) familial cases, 3 out of 14 (21.4%) sporadic cases, 9 out of 68 (13.2%) predisposed cases and 2 out of 40 (5%) control cases showed 1q alterations. None of the 30 lung cancer patients showed chromosome 1 anomaly in this region. This is consistent with the reports on primary breast tumor tissues, cell lines and pleural effusions where 1q defects have been reported. We conclude that chromosome 1q rearrangement might be one of the primary lesions specifically associated with the development of breast cancer. PMID- 1888139 TI - Intrinsic drug resistance in a human medullary thyroid carcinoma cell line: association with overexpression of mdrl gene and low proliferation fraction. AB - Medullary thyroid carcinoma (MTC) is a cancer that is relatively insensitive to clinical chemotherapy. Our previous studies have demonstrated that an established human MTC cell line, TT, seems to possess an intrinsic resistance phenotype when tested for its chemosensitivity to multiple antineoplastic agents. We now report our investigation on the potential mechanisms responsible for the chemoresistance of TT cells. Northern analysis showed an increased level of multidrug resistance gene (mdrl) mRNA in TT and in an inherently drug-resistant colon carcinoma cell line, LoVo, when compared with CEM, a drug-sensitive leukemic lymphoblastic cell line; the latter two cell lines were included here as a control. Verapamil (10 microM) partially reversed resistance to doxorubicin in TT and LoVo cells, but had no effect on doxorubicin cytotoxicity to CEM cells. Expression of glutathione S-transferase-pi (GST pi) gene was undetectable in TT, whereas, under similar conditions, GST pi mRNA was detectable in LoVo. Growth kinetics studies revealed that doubling times of the 3 cell lines in exponential growth were 95, 37, and 24 h for TT, LoVo and CEM, respectively. Flow-cytometric analysis showed that the percentage of TT population is S phase was 49% and 33% of the LoVo and CEM cell populations, respectively, while the G1/G0 fraction of TT was about 63% and 61% higher than that of LoVo and CEM, respectively. Our data suggest that the intrinsic chemoresistance in TT cells may be attributed to the combined factors of overexpression of the mdrl gene, a slower growth rate and a smaller proliferation fraction, although other factors or mechanisms that are yet to be investigated may also act in concert to contribute to the resistance phenotype of TT. PMID- 1888140 TI - Increasing prevalence of the myelodysplastic syndrome. An international Delphi study. PMID- 1888141 TI - Effect on protein synthesis and cell survival of the benzaldehyde derivatives sodium benzylidene ascorbate (SBA) and the deuterated compound zilascorb(2H). AB - Three different benzaldehyde derivatives (viz. beta-cyclodextrin benzaldehyde inclusion compound (CDBA), 4, 6-O-benzylidene-D-glucose (BG) and sodium benzylidene-ascorbate (SBA) have been shown to exert anticancer effects in patients without causing side effects. The anticancer effects are, however, variable and in many cases weak. In a previous study we showed that benzaldehyde with a deuterated formyl group gave rise to a greater protein synthesis inhibition than nondeuterated benzaldehyde. Based on this deuterated benzaldehyde we have synthesized an ascorbic acid acetal; 5,6-benzylidene-d1-L-ascorbic acid (zilascorb(2H). In the present paper we compare the effect of this drug with respect to cell inactivation and inhibition of protein synthesis in human cells cultured in vitro with that of benzaldehyde, BG and SBA. It is shown that zilascorb (2H) is clearly the most effective of these drugs. The effect of zilascrob(2H) is reversible in the sense that protein synthesis regains its normal level shortly (i.e. within 1h) after removal of the drug. Even after protracted treatment inducing a cell kill of more than 99%, the few survivors appear to be without damage after removal of the drug. PMID- 1888142 TI - The role of protein accumulation on the kinetics of entry into S phase following extreme hypoxia. AB - Protein accumulation was measured in human NHIK 3025 cells, synchronized by mitotic selection, during and following treatment with extreme hypoxia (less than 4 ppm O2). Comparison was made between cells treated while in different stages of the G1 phase. The total protein content was measured in individual cells and related to cell cycle phase by coincident recording of DNA and protein using two parametric flow cytometry. After a 24 h treatment with extreme hypoxia, all cells, irrespective of where in G1 they were located at the start of treatment, were reversibly arrested in a pre NDA synthetic stage. During this treatment there was a slight reduction (approximately 2%) in the average amount of protein per cell. The arrested cells were found to display a heterogeneous protein content after treatment, but cells rendered hypoxic while in early-G1, had clearly lost more protein during hypoxia than cells rendered hypoxic while in late-G1. After reoxygeneration, the cells initiated DNA synthesis after first having restored the amount of protein which is normal for these cells at the stage of initiation. Thus, in the first hours following reoxygenation, cells rendered hypoxic while in early-G1 accumulated protein faster than those rendered hypoxic while in late-G1 (the respective rates being 12.3 versus 5.2%/h). We conclude that this protein accumulation may be of importance in restoring the pool of protein required for the initiation of DNA synthesis and that the differences in rate reflect the amount of protein lost during hypoxia. PMID- 1888143 TI - Cytotoxic activity of di-n-butyltin(IV)(X-A-B-Y) compounds related to salicylic acid against human tumour cells. AB - A series of di-n-butyltin(IV) compounds of the type di-n-butyltin(IV)(X-A-B-Y) with the (X-A-B-Y) being related to salicylic acid was tested in vitro for cytotoxic activity against tumour cells of the human A 204, MCF-7, T24, WiDr and IgR-37 cell lines using the PIT method. In each cell line the di-n-butyltin(IV) compounds displayed similar activity. As compared to cisplatin, the compounds were 4- to 10-fold more effective against A 204, MCF-7 and T24 tumour cells and slightly more effective against WiDr cells. The effectiveness against IgR-37 cells was similar for cisplatin and di-n-butyltin (IV) compounds. PMID- 1888144 TI - Metal complexes of ruthenium: a potential class of selective anticancer drugs. AB - Metal complexes of ruthenium were subjected to a number of studies concerning their chemical behaviour and their potential role in medical applications. Particular emphasis was given to the examination of the antineoplastic properties of ruthenium complexes with a number of ligands of biological interest. The possibility of obtaining compounds of potential value in the chemotherapeutic approach to neoplastic disease is supported by observations that ruthenium compounds could interact with tumor cells better than with normal tissues. This interaction can be considered the result of the chemical characteristics of ruthenium ions which can confer much more selectivity than do the actually available and clinically used organic compounds or cis-dichlorodiammine-platinum (II). Thus, ruthenium-based compounds represent the way for introducing a new class of antitumor drugs endowed with a great potential for the management of human tumors. PMID- 1888145 TI - Observations on the antimetastatic action of lysozyme in mice bearing Lewis lung carcinoma. AB - The effects of the oral administration of 100 mg/kg/day of lysozyme chloride on lung metastasis development were studied in mice bearing Lewis lung carcinoma. Lysozyme was administered to mice by supplying the daily amount of lysozyme with the powdered food. Lysozyme treatment reduces lung metastasis development, by significantly reducing the number of metastases of large dimension (diameters greater than 2mm) and by causing a significant increase of the percentage of animals free of large metastases, as compared with untreated controls. Correspondingly, the same animals show a pronounced increase of the number of multinuclear giant cells in the spleen; this parameter appears to be inversely correlated with the antimetastatic effect. These effects support the hypothesis that the antimetastatic effect of orally administered lysozyme depends upon spleen activation and perhaps upon induction of multinuclear giant cells of macrophage origin. This effect is consistent with previous findings indicating the occurrence of host-mediated effects in the antitumor action of lysozyme administered through the oral route. PMID- 1888146 TI - Phenothiazines and calmodulin (review). AB - The cytotoxic properties of the phenothiazines suggest the potential of phenothiazines as antitumor drugs. The following are some important characteristics of phenothiazines for antitumor research: (i) Phenothiazines show an inherent cytotoxicity which can be utilized in the treatment of tumors. (ii) Selective concentration of phenothiazines in tissues such as melanoma and brain tumors can be utilized in the treatment of such tumors. (iii). Structural modifications of phenothiazines with the substitution of a nitrogen atom may lead to more potent cytotoxic agents, particularly when used in combination with radiation. (iv) A synergic effect may be achieved when phenothiazines are used in combination with other agents and conditions. (v) More research is required for understanding the molecular mechanisms responsible for the cytotoxicity of phenothiazines. (vi) Phenothiazines seem to show both antitumor as well as anticarcinogenic properties. The latter property may be utilized in preventing the formation of tumors as well as in the treatment of tumors at very early stages of their development. PMID- 1888147 TI - Expression and partial characterization of estramustine-binding protein (EMBP) in human breast cancer and malignant melanoma. AB - The expression of the estramustine/estromustine-binding protein (EMBP) in human mammary cancer and malignant melanoma was examined by immunochemical methods and compared with that in endometrial and ovarian cancers. By RIA measurements, EMBP was detected in 6/17 mammary cancers (range 11.3-2,660 ng/g tissue) and 2/3 malignant melanomas (618 and 1,240 ng/g), whereas endometrial (n = 6) and ovarian (n = 3) cancers exhibited non-detectable levels. In breast cancer, EMBP expressing tumours were all estrogen receptor-negative, suggesting an inverse correlation between EMBP and hormone responsiveness of the tumour. Biochemical characterization revealed properties of EMBP in mammary tumours and melanomas almost identical to those for EMBP purified from rat ventral prostate: i.e. surface-charge distribution by Mono Q/FPLC ion-exchange chromatography, a molecular weight of 50,000 by gel filtration, and a subunit composition by Western blot analysis under denaturing conditions. Finally, the EMBP immunoreactivity was confined to the cytoplasm of malignant cells in breast cancer and melanoma sections by immunohistochemical examination. This is the first study that demonstrates EMBP in mammary cancer and malignant melanoma. Our findings suggest that a mechanism for selective uptake of cytotoxic estramustine and estromustine is prevailing in these malignancies and that monitoring of EMBP in biopsy samples will be of value in defining patients who may benefit from Estracyt treatment. PMID- 1888148 TI - Localization of endogenous sugar-binding proteins (lectins) in tumors of the central and peripheral nervous system by biotinylated neoglycoproteins. AB - The carbohydrate part of cellular glycoconjugates - glycoproteins, glycoproteins, glycolipids and proteoglycans - and specific endogenous sugar receptors, i.e. lectins, can establish a system of biological recognition based on protein-sugar interactions on the cellular and subcellular levels. To gain insight into the role of proteins in this type of interaction, sections of surgically removed tumor specimens of central and peripheral nervous tissue were analyzed glycohistochemically, using biotinylated neoglycoproteins with different sugar part. A specific staining with this type of probe, exposing different sugar moieties as ligands, indicated the presence of sugar receptors in different types of meningiomas, glioblastomas, gangliocytomas, anaplastic and well-differentiated oligodendrogliomas and ependymomas as well as in neurinomas and neurofibromas of peripheral nerves. In comparison to the well-differentiated ependymomas, the anaplastic form of this tumor exhibited a generally higher capacity to specifically bind the neoglycoproteins, containing alpha- or beta-glucosides. Inverse intensity of the glycohistochemical reaction was observed with galactose 6-phosphate-, galactose-beta(1.3)-N-acetylglucosamine-N-acetyl-D-glucosamine- and mannose- (BSA- biotin), respectively, when anaplastic and differentiated oligodendrogliomas were compared with each other. Tumorously dedifferentiated neurons, i.e. in gangliocytomas, showed a changed spectrum of endogenous sugar receptors in comparison to neurons of normal cerebral cortex. Qualitative and quantitative differences of sugar receptors were observed among the distinct subtypes of meningiomas. Receptors for N-acetyl-D-galactosamine were present only in the anaplastic form, while glucuronic acid-specific receptors were only found in the meningotheliomatous meningiomas. Distinctions in binding spectrum of neoglycoproteins suggest the presence of a possible additional subtype of meningiomas, called submalignant meningioma. Analysis of the spectrum of endogenous sugar receptors can serve to distinguish between different cell populations composing a given tumor, as shown in neurofibromas in the cases of Schwann cells and fibroblastoid cells stained with N-acetyl-D-glucosamine-(BSA biotin). The analysis of expression of endogenous sugar receptors, as part of an intercellular information code system, may represent a further way of studying the mechanism of tumor differentiation and propagation. PMID- 1888149 TI - Comparison of two double labeling techniques to measure cell cycle kinetics in myeloid leukemias. AB - Five patients with acute myeloid leukemia (AML) received a one hour infusion of iododeoxyuridine (IUdR) 100 mg/M2 to label S-phase cells in vivo. The aspirate was labeled in vitro either with tritiated thymidine (3HTdr) or bromodeoxyuridine (BrdU) to measure the duration of S-phase (Ts). The mean Ts using 3HTdr (Ts1) was 15.9h (13.1-19.8h) and using BrdU (Ts2) was 17.1h (14.5-20.6h). Total cell cycle time (Tc) ranged between 44.7h to 158.8h using Ts1 and 54.0h to 170.5h using Ts2. Based on this close approximation between the results, we confirm the reliability of the newly developed method that relies purely on immunohistochemical reaction. PMID- 1888150 TI - Adoptive immunotherapy of solid tumors with activated macrophages: experimental and clinical results. AB - Adoptive immunotherapy in cancer has been essentially restricted to the use of lymphoid effector cells (NK, TIL, LAK) stimulated with IL-2. Differentiated macrophages represent another key effector population even more important for the immune control of cancer. We have shown that activated murine macrophages reduced primary tumors and experimental metastases. Human macrophages differentiated from circulating monocytes and activated with IFN gamma (MAK) were cytotoxic in vitro for a variety of tumor cell and caused regression of human tumors implanted in nude mice. A large scale technology has been developed for the generation of antitumor macrophages. These MAK cells (10(8) to 10(9] were injected in cancer patients in pilot clinical trials and were well tolerated. MAK treatment is technically feasible, clinically safe and presents several advantages compared to other immunotherapies. PMID- 1888151 TI - Expression of a new surface membrane antigen (SQM1) in tumor cells cultured in media with different calcium ion levels. AB - Terminal differentiation is usually achieved in normal as well as transformed squamous epithelial cells when cultured. On the other hand, tumor cells at various differentiation stages and with different biological characteristics comprise the heterogeneous properties of tumors which have been one of the barriers to effective treatments. Recently, a surface membrane protein has been reported in squamous cell carcinomas of the head and neck, which is recognized by a murine monoclonal antibody, SQM1. This glycoprotein was further suggested to be related to squamous cell differentiation and intercellular adhesion. In a recent study, the esophageal carcinoma cells of EC/CUHK2 cell line were induced to various differentiation stages as evidenced by the increasing amount of intracellular desmosomes and tonofilaments and greater binding ratios of cytokeratin and involucrin antibodies than in those cells that maintained lower calcium ion concentrations. The expression of SQM1 antigen was found to increase in intensity when the tumor cells were cultured in moderate to high calcium ion levels for 10 to 15 hours when the differentiation patterns were beginning to appear. The intensity declined gradually thereafter. Thus SQM1 protein might be related to the stage when the cells started committing with squamous differentiation. PMID- 1888152 TI - Effects of polyunsaturated fatty acids on vincristine-resistance in human neuroblastoma cells. AB - PUFAs such as GLA (n-6) or DHA (n-3) were shown to exert antitumor activity on a human neuroblastoma cell line (NCG) and its VCR-resistant subline (NCG/VCR1, 8.6 fold resistant to VCR) in vitro. The NCG/VCR1 line had markedly decreased intracellular accumulation of [3H]-VCR and an accelerated drug efflux, compared to the NCG. The cytotoxic activity of PUFAs was correlated with the generation of MDA-like products in these cells. When VCR was added simultaneously with GLA or DHA to culture medium, the cytotoxic effect of VCR was about 2-fold enhanced, accompanied by about 1.5-2.0-fold increase of intracellular [3H]-VCR in both cell lines. Fatty acid analysis of membrane phospholipids of the NCG and the NCG/VCR1 cells treated with GLA or DHA showed an increased total PUFAs and SFAs, associated with markedly decreased total MUFAs and an inverted PUFAs/MUFAs ratio. Such phospholipid modification may have altered the membrane physical properties and enhanced the VCR cytotoxicity by increasing intracellular VCR accumulation; however, these PUFAs did not affect the drug efflux sufficiently enough to overcome completely the VCR resistance in the NCG/VCR1 cells. These results indicate that PUFAs partially alleviate the VCR-resistance in human neuroblastoma cells, not directly acting on VCR-resistance mechanism(s). PMID- 1888153 TI - Effect of diverse categories of drugs on human colon tumour cell proliferation. AB - The effect of a number of drugs belonging to different therapeutic categories on cell proliferation in a human colon cancer cell line (HT 29) was studied. Generally, drugs classified as calcium antagonists had a moderate to strong inhibitory effect on cell growth. The EC50 value for prenylamine, perhexiline and bepridil was 10 microM. The so-called calcium channel blockers (verapamil, nifedipine, diltiazem) were less effective. With the exception of the sodium selective ionophore, monensin, which was extremely potent (EC50 less than 0.1 microM), calmodulin antagonism appeared to be a common feature of compounds inhibiting cell proliferation of human colon tumour cells. PMID- 1888154 TI - High dose intensity of cisplatin and etoposide in adenocarcinoma of unknown primary. AB - Adenocarcinoma of unknown primary (AUP) has generally a poor prognosis. Previous studies have suggested that Cisplatin and Etoposide have activity in AUP. The aim of this study was to determine if dose intensification of this combination would result in increased efficacy. Each 28 day cycle consisted of Cisplatin 100 mg/m2 given on Day 1 and 8 with Etoposide 80 mg/m2 given on day 1, 2, 8 and 9. Sixteen patients (Pts) with no prior chemotherapy were accrued to this study. Predominant sites of disease were lung, liver, and bone. BHCG and AFP were not elevated. One complete remission was seen in a patient with a mediastinal mass (duration of remission = 59 weeks). Two other patients had a partial response. Overall response rate was 19%. Moderate to severe renal toxicity was recorded in 8 patients, with neuro- and ototoxicities in 2 patients each. Severe granulocytopenia occurred in 8 patients, and one patient died of congestive heart failure on day 1 of cycle 2. This excessive toxicity, without enhanced efficacy does not encourage a more extensive empiric trial by this dose schedule in the treatment of AUP. PMID- 1888155 TI - Relationship between tumor growth and cachexia during progressive malignant disease: a new measure of the extent of cachexia, the cachexia index. AB - The relationship between the dynamics of tumor growth and the development of cachexia in C57b1/6j mice bearing the syngeneic transplantable adenocarcinoma EO 771 has been studied. The tumors grow independently of the inoculum size according to the Gompertzian mode of growth, with a maximum growth rate at a tumor size of about 3 g. As a dynamic measure of the degree of cachexia, the cachexia index "K", i.e. the quotient of the alteration of the carcass weight of the animal divided by the alteration of the tumor weight during the same time interval, is introduced. K is superior to a simple estimation of the alteration of the carcass animal weight because it also considers local weight-reducing effects of the infiltrating tumor growth. With respect to cachexia, three phases of tumor growth can be distinguished; cachexia develops mainly during the 2nd phase, i.e. for tumor sizes between 1.0 to 3.5 g which strongly correlates with the maximum growth rate of the tumor. PMID- 1888156 TI - Intravesical Bacillus Calmette-Guerin treatment for superficial bladder cancer: results after 15 years of experience. AB - Superficial bladder cancer has a high recurrence rate and considerable progression rate. The treatment currently consists of resection and adjuvant intravesical chemotherapy or immunotherapy. Intravesical instillation of Bacillus Calmette-Guerin (B.C.G.) is considered to be one of the most successful immunotherapies in man. Durable response rates of 60-70% are achieved. Toxicity is more pronounced in comparison with intravesical chemotherapy. In this article we describe the experience with B.C.G. during the last 15 years. No consensus has been reached yet about the ideal treatment scheme, appropriate strain and optimal dosage. The mechanisms of action are complicated and still not completely understood. PMID- 1888157 TI - Immunotherapy of bovine ocular squamous cell carcinoma: isolation, culture and characterization of lymphocytes present in the tumor. AB - Bovine ocular squamous cell carcinoma (BOSCC) is sensitive to intralesional immunotherapy with BCG or recombinant human IL-2 (rhIL-2). The mechanism of tumor regression is as yet unclear. Alterations in the concentration of IL-2 (and possibly other factors) in the tumor, due to regional injection or induction by BCG, may induce killer cell activity and thus tumor regression. To investigate this, lymphocytes were isolated by mechanical fractionation of biopsies of BOSCC. Growth, phenotypical, and functional characteristics were studied. TIL could be isolated and grown from all biopsies of BOSCC. An estimated increase in cell number of 50-150 fold was observed during 5-7 weeks of culture. FACS analysis of a limited number of the TIL cultures showed a characteristic shift in phenotypes until day 28 of culture. CD2+ cells (50-70%), and as a consequence of this CD2- cells, remained stable in number. The number of CD8+ cells increased. CD4+ cells were detected in low numbers by day 28. Prolonged culture resulted in an increase of CD2- gamma delta + cells, CD2+4-8- cells, and occasionally of both CD8+ and CD2+ cells. In 51Cr release assays TIL showed cytotoxicity for BOSCC-derived tumor cell lines in general, which increased transiently by cocultivation with tumor cells. Killing of YAC-1, and P815 was far less efficient. Preferential killing of autologous cell lines was not seen. In conclusion, TIL from bovine ocular squamous cell carcinomas can be cultured in the presence of rhIL-2, which induces cytotoxic activity for BOSCC-derived tumor cells. Cells responsible for killing in vitro and potentially for regression of the tumor after immunotherapy with BCG or rhIL2 cannot yet be identified. Depletion and blocking experiments are being conducted in order to identify the cells (CD2+8+, CD2-gamma delta + or other CD2 +/-) responsible for killing. PMID- 1888158 TI - Membrane transport of methotrexate in a squamous carcinoma cell line adapted to low folate concentrations. AB - Membrane transport characteristics of the folate analogue methotrexate (MTX) were studied in a human squamous carcinoma cell line of the head and neck (HNSCC) adapted to grow in tissue culture media with nanomolar reduced folate concentrations (SCC-11B-LF), as compared to SCC-11B cells grown in standard medium containing high folate concentrations. We observed that SCC-11B-LF cells exhibited a 10.5-fold increased uptake of [3H]-MTX via the reduced folate/MTX carrier system compared to SCC-11B cells. Affinity labelling of the reduced folate/MTX carrier system suggests that the up-regulation of [3H]-MTX transport mainly results from an increased rate of carrier translocation, and only to a minor extent (15-20%) from an increased amount of carrier protein. The upregulation of MTX transport resulted in a 2.4-fold increased growth inhibitory effect by MTX. These results suggest that membrane transport may play a more important role in MTX-cytotoxicity when SCC-11B cells in vitro are grown in more physiological folate concentrations. PMID- 1888159 TI - Splenectomy abolishes antitumor effect of immunotherapy with streptococcal preparation, OK-432, on mouse liver tumors. AB - In the present study, we investigated the therapeutic effects of oral and subcutaneous administration of OK-432 prior to or following the transplantation of murine liver tumors. In addition, the effect of splenectomy on the antitumor activity of OK-432 was investigated. Mice which received OK-432 orally prior to tumor transplantation exhibited significantly lower tumor weight and significantly improved survival, when compared to the control mice. Prior subcutaneous injection of OK-432 did not show any antitumor activity. On the other hand, both oral and subcutaneous administration of OK-432, subsequent to tumor transplantation, led to a significant improvement of survival and a decrease in the number of lung metastases, although tumor weight was not affected. The anti-tumor effect of OK-432 required the presence of the spleen, since the survival of the mice with liver tumors was not improved by OK-432 if splenectomy and tumor transplantation were performed simultaneously. These results suggest that immunotherapy with OK-432 may beneficial in the treatment of liver tumors and that these effects are dependent on the presence of the spleen. PMID- 1888160 TI - Reversing multidrug resistance in L1210 tumor cells by hycanthone or chlorophenoxamine in vitro and in vivo. AB - In the presence study we demonstrated that hycanthone and chlorophenoxamine can modulate the resistance of multidrug resistant (MDR) murine L1210 leukemia tumor lines in vitro and in vivo. The circumvention of MDR by hycanthone and chlorophenoxamine in vitro was demonstrated by a short-term test using tritiated nucleic acid precursors and by flow cytometrical measurement of accumulation of rhodamine 123. Furthermore, we treated mice bearing resistant L1210 ascites cells with doxorubicin and hycanthone or chlorophenoxamine. Hycanthone in combination with doxorubicin significantly inhibited tumor growth. We also found an improved therapeutic effect of doxorubicin plus chlorophenoxamine. Our results in vitro and in vivo indicate that hycanthone and chlorophenoxamine might be appropriate tools for the circumvention of MDR in human tumors. PMID- 1888161 TI - Vitamin B6 and cancer: a novel pyridoxal 5-phosphate conjugate in tumor cells and blood of cancer patients. AB - Studies on the metabolic transformations of labeled pyridoxine showed that its utilization by tumor animals and tumor cells differs greatly from that seen in control animals. When [3,4-14C] and/or tritium labeled pyridoxine at the 6th ring carbon is administered i.p. to tumor-bearing animals and its fate is subsequently determined at different time intervals (using HPLC separation of the labeled metabolites following acid extraction from tissues), in addition to other differences, synthesis of a novel labeled product occurs which begins with the onset of tumor growth. It is either absent or present only at minimal levels in normal animals and regenerating rat liver. It is present in all tumor sources examined to date, i.e. serum of tumor rats, a spectrum of rat hepatomas, solid human tumors, tumor cells in culture and plasma of cancer patients. The novel product is a conjugate of pyridoxal 5'-phosphate with the structure Adenosine-N6 Diethylthioether-N1- Pyridoximine-5'-phosphate. This communication reports on the occurrence and distribution of the novel product in different tumor tissues and cells as well as the blood of cancer patients with active disease and in remission, and in normal volunteers. The results show significantly higher levels of this product in the blood of patients with different malignancies and in the active state. The novel vitamin B6 compound may be a good candidate as a marker for tumor presence and/or metastasis. PMID- 1888162 TI - Antiinvasive activity of hexadecylphosphocholine in vitro. AB - The antiinvasive and related effects of hexadecylphosphocholine (HePC), a newly synthesized antitumor phospholipid, were studied on malignant murine MO4 cells in vitro and compared to the effects produced by racemic - 1 - 0 - octadecyl - 2 - 0 - methylglycero - 3 - phosphocholine (ET-18-OCH3), the prototype of ether lipids. The effects on cell survival produced by both drugs, determined through the 3 (4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium-bromide test, was moderate at the antiinvasive concentration of 30 micrograms for HePC and 10 micrograms for ET 18-OCH3 per ml. Growth in suspension culture and directional migration from MO4 spheroids explanted on solid substrate was reduced in the presence of 30 micrograms HePC per ml. Invasion of MO4 cells into precultured heart fragments (PHF) was variably inhibited in the presence of 30 micrograms HePC per ml, while the antiinvasive effect on two epithelial lines was more complete. Invasion was also inhibited in PHF pretreated with 30 micrograms HePC and 10 micrograms ET-18 OCH3 per ml for 48 hours followed by confrontation with MO4 spheroids in drug free medium. This inhibition of invasion was maintained when PHF was pretreated and kept in drug-free medium for 7 days before confrontation with MO4 spheroids. It was our impression that this phenomenon was more obvious with ET-18-OCH3 than with HePC. After pretreatment of PHF followed by 7-day incubation in drug free medium, a larger shift towards higher molecular weight of the N-linked cell surface glycosylpeptides (N-GP) was observed with ET-18-OCH3 than with HePC. Removal of terminal sialic acid moieties abolished the shift in PHF pretreated with HePC or ET-18-OCH3 followed or not by further incubation in drug-free medium. The antiinvasive effect on the malignant epithelial cells was complete at 30 micrograms HePC per ml. Areas of differentiation in close contact with the PHF were obvious. We concluded that both ET-18-OCH3 and HePC had antiinvasive activity in vitro. For MO4 cells, this antiinvasive activity was less variable with ET-18-OCH3 than with HePC. PMID- 1888163 TI - In situ lactate dehydrogenase patterns as markers of tumour oxygenation. AB - The histochemical patterns of lactate dehydrogenase, LDH, are here proposed as indicators of the local levels of oxygenation of malignant tissue. This parameter has outstanding importance in determining the tumour aggressiveness and response to treatment. The tetrazolium salt reaction previously proposed for the mapping of hypoxia has been improved by the use of polyvinyl alcohol as a tissue stabilizer. The intracellular coloured products of this reaction appear in two distinct forms, diffuse and granular, which we previously postulated to be indicative of LDH isoenzymes soluble and bound, respectively. Solubility is promoted by H-LDH subunits preferentially synthesized under good oxygenation; binding to membranes is favoured by the presence of M-LDH subunits preferentially active under poor oxygeneration. A reversible shift between the two forms apparently regulates the cells' metabolic adaptation to different stress situations. We assume that the anoxic shock protein LDHk exists exclusively in the bound form. In the Ehrlich carcinoma model previously employed, we verify a drift towards the exclusive presence of the granular form as the section's depth increases and/or when the cuff width decreases. This trend is ascribed to a progressive worsening of the local oxygenation levels. At the tumour interface, a chronic inflammatory tissue (notoriously highly hypoxic) is characterized by a granular LDH activity. New models of hypoxia are proposed and discussed for explaining the patterns here described and observed also in other studies, namely those derived from hyperviscosaemia, damaged endothelia, fibrosis, anaemia, poor ventilation and impaired cardio-vascular system. PMID- 1888164 TI - Different chemosensitivities of rat 3Y1 fibroblasts transformed by various agents in vitro. AB - Alterations of chemosensitivities associated with transformation of rat 3Y1 fibroblasts were compared among various agents, including either adenovirus type 12 (Ad12-3Y1), the E1A region of adenovirus type 12 (E1A-3Y1), mouse polyoma virus (Py-3Y1), Simian virus 40 (SV-3Y1), Rous avian sarcoma virus (SR-3Y1), plasmid DNA carrying v-Ha-ras oncogene (HR-3Y1), or N-methyl-N'-nitro-N nitrosoguanidine (NG-3Y1), with untransformed 3Y1 fibroblasts, using a semiautomated non-clonogenic MTT assay. IC50 values were compared for each drug in each cell line. Among the different cell lines, untransformed 3Y1 cells were the most resistant to cisplatin (CDDP), adriamycin (ADM), carboquone (CQ), bleomycin (BLM), mitomycin C (MMC) and 4-hydroperoxy cyclophosphamide (4-hp-CPA). On the other hand, E1A-3Y1 cells were more resistant to vincristine (VCR) and NG 3Y1 and Ad12-3Y1 were more resistant to 5-fluorouracil (5-FU) than untransformed 3Y1 cells. These transformed lines did not display any cross-resistance to other drugs. The dissociation of chemosensitivities between Ad12-3Y1 and E1A-3Y1 to ADM, VCR and 5-FU was recognized. These results suggested that some of these transforming agents may alter the chemosensitivities of anticancer drugs. PMID- 1888165 TI - Increased plasma free tryptophan levels in human cancer: a tumor related effect? AB - High free tryptophan (F-TRP) plasma levels are found in cancer patients (CP). F TRP plasma concentrations are affected by the levels of its carrier, albumin (ALB), and free fatty acids (FFA) competing with TRP for ALB binding sites. The lack of correlation between F-TRP, ALB and FFA in CP suggests a tumor-dependent effect on the rise in F-TRP. To verify this hypothesis, F-TRP, ALB and FFA levels were assayed in 12 lung and 16 breast CP susceptible to radical surgery, before and 15 days after surgical removal of the tumor. F-TRP levels significantly decreased after tumor ablation. Since no correlation was found between F-TRP, ALB and FFA variations, it is conceivable that the tumor itself may be responsible for the high F-TRP levels in CP. PMID- 1888166 TI - Inhibition of human DNA ligase by anthracyclines and distamycins. AB - Antitumor anthracyclines and distamycins behave as strong inhibitors of human replicative DNA ligase. The enzyme appears sensitive to a specific occupancy of the minor groove of DNA. Inhibition by anthracyclines takes place after enzyme adenylation, does not correlate with DNA unwinding potency but strictly correlates with the presence of an amino group on the sugar. In contrast to the non-toxic distamycin A, its antitumor derivative FCE24517 inhibits DNA joining, enzyme adenylation and AMP-driven DNA topoisomerisation. Our data favour a model in which multiple enzymic targets contribute to the activity of these antitumor drugs. PMID- 1888167 TI - Progesterone-binding cyst protein (PBCP = GCDFP-24) and steroid hormone receptors as markers of differentiation in breast cancer. Inverse relation of distribution in normal and malignant tissue of the same breast. AB - Progesterone-binding cyst protein (PBCP, identical to Gross Cystic Disease Fluid Protein; GCDFP-24) has been evaluated as a possible marker of differentiation in breast tissues. In 17 women with verified operable breast cancer, we have quantitated the cytosol content of PBCP, steroid hormone receptors (estrogen receptor[ER], progesterone receptor[PR] and androgen receptor[AR] as well as albumin in specimens from the primary tumor and from the adjacent non-malignant tissue of the same breast. A significantly higher amount of PBCP (p less than 0.001) and albumin (p less than 0.003) was found in the non-malignant tissue. Conversely, the content of steroid receptors was significantly higher (p less than 0.001) in the malignant tumor, compared to the non-malignant breast tissue. A significant correlation (p = 0.005) between PBCP content in the malignant tumor and in the non-malignant tissue was found. In malignant tissue, ER was significantly correlated with AR (p = 0.007) and to age at operation (p = 0.006). Our results are in agreement with recent reports on other tissue parameters, which indicate qualitative and quantitative differences between the malignant and the non-malignant counterpart with regard to regulation of cell growth and the expression of differentiation markers. This study provides evidence for PBCP as a marker of differentiation to be implemented in further clinical and basic research on breast cancer. PMID- 1888168 TI - Effect of unlabelled monoclonal antibodies on the biodistribution of 111In labelled anti-prostate-specific acid phosphatase monoclonal antibodies in the mouse model. AB - In order to optimize methods developed for the radioimaging of prostatic cancer, the effect of unlabelled monoclonal antibodies (MoAbs) on the biodistribution of 111In-labelled MoAbs was studied in nude mice carrying human prostatic cancer xenografts (PC-82). Since the intact IgG and its F(ab')2 fragment have different clearance patterns from the blood, we also studied which of these antibody forms is preferable for use as the unlabelled antibody, when injected prior to, simultaneously with, or following the injection of the labelled antibody. Due to their faster blood clearance, F(ab')2 fragments displayed higher tumour-to-blood ratios than the corresponding anti-prostate-specific acid phosphatase (anti-PAP) IgG1. However, tumour-to-blood ratios increased when the amount of the labelled anti-PAP-IgG1 was increased (from 10 micrograms to 25 micrograms) and the biodistribution measurements were carried out after a prolonged period (216 h). When a combination of labelled IgG1 (1, 10 micrograms) and unlabelled IgG1 (200 micrograms-300 micrograms) was used, tumour-to-blood ratios could not be improved. Contrary to what was observed with the intact IgG1, labelled F(ab')2 fragments did not display a dose-dependent accumulation in the tumour. A combination of labelled F(ab')2 fragments and unlabelled IgG1 resulted in a slight increase in tumour-to-blood ratios, but the administration of labelled F(ab')2 fragments with unlabelled F(ab')2 fragments resulted in a significant decrease (p = 0.04) in tumour-to-blood ratios. Liver-to-blood ratios could be decreased by using either a combination of unlabelled and labelled IgG1 (at ratios of 30:1, or 200:1), or a combination of unlabelled IgG1 and labelled F(ab')2 fragments (at ratios of 50:1, or 100:1), or a combination of the unlabelled and labelled F(ab')2 fragments (at a ratio of 50:1). The decrease of liver-to-blood ratios was independent of the mode of administration of the unlabelled substances. A "rinse" with an additional dose of unlabelled IgG1, 24 h before the sacrifice, resulted in even lower liver-to-blood ratios. The results obtained from this study suggest that, of the combinations investigated, to increase tumour-to-blood ratios and decrease liver-to-blood ratios thereby improving the radioimaging of prostatic cancer, the best one consists of 111In labelled anti-PAP-F(ab')2 fragments and unlabelled anti-PAP-IgG1. PMID- 1888169 TI - Cis-platin responsive sequences in the human c-myc promoter. AB - We have transfected recombinant plasmids carrying 5' c-myc sequences linked to the reporter gene chloramphenicol acetyl-transferase (cat) and to the selectable marker aminoglycoside phosphotransferase (aph) into rat fibroblasts and obtained stable transfectants. The response to cis-platin of these cell lines was studied. At 5 X 10(-5) M concentration cis-platin stimulates cat gene expression 9 and 11 fold respectively in cell lines containing constructs with c-myc promoter sequences truncated at -2319 and -350 relative to c-myc RNA start site P1. A third cell line expressing a myc/cat recombinant truncated at -290 shows no response to cis-platin, thus defining a cis-platin responsive element between coordinates -290 and -350 on the myc promoter region. PMID- 1888170 TI - Oncogene transfection of mink lung cells: effect on growth characteristics in vitro and in vivo. AB - Three sublines have been derived from the parental line Mv1Lu by transfection with normal and mutated Ha-ras, and myc oncogenes, and subsequent cloning. All the oncogenes have increased the growth rate of the cell in vitro, increased their plating efficiency in monolayer and suspension, and reduced their serum dependence. Growth in vivo as xenografts in nude mice has also been increased. Very few tumours were generated from the parental line and those that did form did so after a prolonged lag period, while the transfected lines produced tumours with 100% efficiency, and a short lag period. In general the effects of ras transfection were more extreme, with the highest growth rates and plating efficiencies in vitro and the shortest lag period and doubling times in vivo. There was no increase in plasminogen activator activity as a result of transfection, and the invasive behaviour of the lines in organotypic culture was broadly similar. PMID- 1888171 TI - The effect of H-ras oncogene transfection on response of mink lung epithelial cells to growth factors and cytotoxic drugs. AB - Mink lung epithelial cells were transfected with c-myc and activated H-ras genes. The transfected sublines formed colonies in soft agar and were tumorigenic when injected subcutaneously into athymic nude mice. DNA synthesis was measured in each of the cell lines by 3H-thymidine incorporation and in the parent line there was dose related stimulation of DNA synthesis by epidermal growth factor (EGF) and inhibition by transforming growth factor-beta (TGF-beta). The c-myc transfected line had a reduced inhibitory response to TGF-beta and an exaggerated stimulatory response to EGF whereas the activated H-ras1 transfected line did not respond to TGF-beta or EGF. The activated H-ras1 transfected line was significantly more resistant to doxorubicin (ID50, 4.4 nM) and vincristine (ID50, 4.9 nM) than the parent mink lung epithelial cell line (ID50, 2.7 nM and 2.4 nM respectively). It would appear that oncogene transfection can alter the sensitivity of mink lung epithelial cells to both exogenous growth factors and cytotoxic drugs. PMID- 1888172 TI - In contrast to EGFr gene overexpression, H-ras gene expression decreases in human gliomas. AB - We have examined the expression of the epidermal growth factor receptor (EGFr) gene and 14 other oncogenes in several human gliomas. EGFr overexpression was apparent in 17 of 18 tumors. Nevertheless, remarkable amounts of aberrantly-sized EGFr mRNAs were not found in the 11 tumors examined. Among the 14 other oncogene probes employed, only the H-ras probe revealed changes in the expression level. The expression of this oncogene was 2-3-fold reduced in 13 of 18 tumors. In neural tissue the H-ras gene expression can be correlated with cellular differentiation. A correlation between H-ras protein expression and a favourable clinical prognosis was found in neuroblastomas. The decreased amounts of H-ras transcripts in gliomas may be a sign of a lower state of differentiation of the cells. PMID- 1888174 TI - The influence of once or twice daily irradiation regimens on growth of squamous cell carcinoma spheroids of different diameters. AB - Large tumours are in general more difficult to cure by radiation treatment than small tumours. Several factors may be responsible for this phenomenon which evolves during tumour growth. In an earlier study using squamous cell carcinoma cell line HN-1, we have shown in split-dose recovery experiments that the amount of sublethal damage repair is equal in spheroids of different diameters. To elucidate this repair capacity further, we have employed other radiation regimens, calculated with the LQ-equation to be iso-effective, in spheroids of different sessions. Using specific growth delay to quantify radiation response after two to five fractions, it was shown that repair capacity was equal in spheroids of different sizes. For small spheroids the specific growth delay was smaller in once daily fractionation regimens than when radiation was administered in twice daily sessions. In large spheroids this advantage of accelerated fractionation was not observed. If spheroids from this squamous cell carcinoma cell line may be regarded as a relevant model system for their in vivo counterparts, then the results from the present study may indicate that accelerated fractionation of treatment is advantageous for small lesions, but not for larger tumours. PMID- 1888173 TI - Pleural fluid and serum soluble interleukin-2 receptors in pleural effusions. AB - Pleural fluid and serum soluble Interleukin-2 receptors (sIL-2R) were measured by an enzyme-immunoassay in 13 patients with tuberculous pleurisy, in 28 patients with carcinomatous pleurisy and in 17 transudates from patients with congestive heart failure. Significantly higher values of sIL-2R were observed in exudative than in transudative (mean +/- SEM = 713 +/- 111 U/ml) pleural fluid samples, the highest being found in tuberculous (3777 +/- 501 U/ml) and the intermediate in carcinomatous exudates (1981 +/- 160 U/ml) (p less than 0.0001; on way ANOVA). Serum sIL-2R were significantly higher in carcinomatous and transudative groups than in age- and sex- matched controls (p less than 0.002; one way ANOVA), while there was no significant difference between the tuberculous group and controls. The pleural/serum sIL-2R ratio was significantly higher in tuberculous (5.32 +/- 0.60), than in carcinomatous pleurisy (2.67 +/- 0.20) and higher still than in transudates (0.76 +/- 0.10) (p less than 0.001; one way ANOVA). In conclusion, the pleura/serum sIL-2R ratio may be a helpful parameter in differentiating tuberculous from carcinomatous pleurisy and an additional confirmatory one for distinguishing transudates from exudates. PMID- 1888175 TI - Inhibition of influenza A virus replication by a kanamycin derivative. AB - We studied the antiviral activity and the mechanism of action of a new antiviral agent and kanamycin derivative, 1-N-eicosanoyl-3"-N-trifluoroacetyl kanamycin A (ETKA), against influenza A virus. From yield reduction assays with VERO cells, ETKA showed a significant antiviral activity with negligible cytotoxic effect. In the presence of 20 micrograms/ml of ETKA at which VERO cell growth was not inhibited, virus titer was suppressed to 11.2% of control, and at 100 micrograms/ml virus production was suppressed to more than 99%. ETKA markedly inhibited viral protein synthesis when cells were pretreated with the drug before infection, but there was no inhibition when the drug was added 15 min post infection. ETKA did not inhibit virus adsorption and penetration. Nor did it affect the activity of viral RNA polymerase in vitro. We found that the drug had a direct inactivating effect on influenza A virus under acidic conditions. These results suggest that ETKA exerts its antiviral action mainly in the early stage, prior to uncoating by direct inactivation of the virus due to the acidic environment of the endocytic vesicle. Aerosol treatment with the drug protected mice against a lethal influenza A virus infection. PMID- 1888176 TI - Synthesis and anti-HIV activity of some haloalkyl phosphoramidate derivatives of 3'-azido-3'-deoxythymidine (AZT): potent activity of the trichloroethyl methoxyalaninyl compound. AB - Phosphate triester derivatives of AZT have been prepared as membrane-soluble pro drugs of the bio-active nucleotides, and have been evaluated against HIV-1 in vitro. In particular, the phosphorus centre carries a trichloro- or trifluoroethyl group and a carboxyl-protected, amino-linked amino acid. The compounds are prepared using phosphorochloridate chemistry, and are characterized by a range of techniques. They display potent anti-HIV activity and low host toxicity, but surprisingly this activity does not increase on the introduction of the haloalkyl moiety. The trichloroethyl methoxyalaninyl compound is exceptional: here the activity is enhanced 50-fold by the introduction of the trichloroethyl group. PMID- 1888177 TI - [Minimal residual disease in leukemia]. AB - Recently, detection of the minimal residual disease (MRD) has become possible by polymerase chain reaction (PCR) using leukemia specific DNA or mRNA sequences originated from t(9; 22), t(1; 19) and t(14; 18) translocations, T cell receptor or immunoglobulin CDRIII. This method made possible to detect one leukemic cell out of 10(4)-10(5) cells, and the presence of MDR became clear during complete remission after chemotherapy or bone marrow transplantation. This suggests the usefulness of this method in the treatment of leukemia. PMID- 1888178 TI - [Recent progress in the treatment of oral and pharyngeal cancer]. AB - Today, in the treatment of oral cancer, combined resection and reconstructive surgery has shown marked progress. Especially, the surgical procedures of bone graft after mandibulectomy have been seen widespread application. In the treatment of nasopharyngeal cancer, adjuvant chemotherapy after therapeutic dose of irradiation indicates a better survival rate than radiation alone, and in advanced nasopharyngeal cancer, a wide resection is effective for cure. In the surgical treatment of hypopharyngeal cancer, by the immediate reconstruction of pharynx with jejunum, patients can eat orally in a short time. The most important problem in the treatment of head and neck cancer is development of effective chemotherapy against distant metastases. PMID- 1888179 TI - [A combined therapy for maxillary cancer]. AB - Forty-three patients with cancer of the maxillary sinus were treated by surgery combined with radiation and regional chemotherapy as a series of treatment in 1978-1989. The combined therapy consisted of the followings: 1) Operation to reduce tumor-mass. 2) Irradiation of total dose of 16 Gy, that is, 8 Gy preoperatively and 8 Gy postoperatively. 3) Chemotherapy with arterial infusion of 1,000 mg fluorouracil (5-FU) and 2,000 mg broxuridine (BUdR) for 4 days after operation. Of the 16 patients with neck metastasis, 14 accepted extirpation of the metastatic cervical lymph nodes and upper neck dissection was performed in other 2 cases. Five-year survival was 87% in the 32 patients of stage II and III but 41% in the 11 of stage IV. The combined therapy for patients of stage II and III disease is recommended because of the satisfactory results. However, a further study is required in our therapeutic schema for the case of stage IV since the prognosis was poor. PMID- 1888180 TI - [Classification of DNA histogram perturbed with 5-FU and its clinical application]. AB - Analysis of cell kinetics may be beneficial for evaluation of the therapeutic effect of anticancer agents. Therefore, using flow cytometry, the authors could classify perturbations of DNA histogram of cultured colon cancer cells treated with 5-FU into 4 types. Perturbation of DNA histogram of cancer cells treated with 5-FU of different concentrations was closely associated with the degree of cell damage indicated by the growth curve. Then, tumor samples before and after injection of 5-FU were collected from 9 preoperative patients with colon cancer and classified into the above 4 types. The results show that 2 cases were classified into type I (S/G1 ratio: 1.5 greater than, G1.G2M comparison: G1 greater than G2M) and another two into type IV (CV ratio: 1.5 less than or equal to, S/G1 ratio: 1.5 less than or equal to, G1.G2M comparison: G1 greater than G2M). However, 5 cases could not be classified (not evaluated) because of the absence of stemline and the presence of heterogeneity in tumor samples. The authors consider that the classification of perturbation of DNA histogram is a useful method to evaluate the degree of cell damage with 5-FU, if tumor samples are appropriately selected and analysis is made with careful attention. PMID- 1888181 TI - [Analysis of tumor cell growth and effects of antitumor drugs on cell cycle regulation by flow cytometry]. AB - Relationship between tumor cell growth and cell cycle and influence of antitumor drugs on the cell cycle regulation were investigated by the use of murine EL-4 tumor. Cell growth curve of EL-4 cells was well related to the cell cycle pattern analyzed by two color flow cytometry both in vivo and in vitro. The ratio of S phase rapidly increased in early log phase and decreased from late log to plateau phases. The ratio of G0/G1 phase showed a reciprocal change. Minimum effective doses of 5-fluorouracil (5-FU) and CDDP on EL-4 growth in vitro were 1 x 10(-6) M and 0.5 micrograms/ml, respectively. At such doses, 5-FU showed an accumulation in early S phase and CDDP showed a partial synchronization in S phase and subsequent accumulation in late S and G2 + M phase. In case of in vivo administration with 5-FU (20 mg/kg/day) ratio of S phase was higher than in untreated control mice at day 2-3 but decreased rapidly thereafter. Mice administered with CDDP (5 mg/kg/day) showed a decrease in S phase from day 2 and completely rejected the tumors by day 5. From these results, each phase of cell cycle was influenced by the cell growth characteristics and the cell cycle pattern was dynamically changed according to the mode of action of antitumor drugs. Moreover, in vivo effects of these drugs can be evaluated adequately by the analysis of the cell cycle. PMID- 1888182 TI - [Effect of UFT by oral administration using a murine hepatic metastasis model]. AB - We examined the antitumor effect of UFT, a 5-FU derivative using a hepatic metastasis model in mice. BALB/c and CDF1 mice were given orally UFT (30 mg/kg, 50 mg/kg daily or 120 mg/kg every other day) for 20 days after inoculation of colon-26 tumor cells into the portal vein. The number of metastatic nodules and the weight of the liver decreased significantly in all groups of UFT treatment. The therapeutic effect with 50 mg/kg UFT was better than those with the other doses. NK and LAK activities of spleen cells obtained from UFT-treated tumor bearing mice were not significantly different from the untreated control. IL-1 and IL-2 production of the spleen cells were also not significantly changed by the treatment with UFT. These results suggested that the oral administration of UFT represents an antitumor effect against hepatic metastasis in mice without sever suppression of the host immune system. PMID- 1888183 TI - [Hepatic infusion-chemotherapy of liver metastases from stomach cancer- comparative study for intraarterial group and non-intraarterial group]. AB - Metastasis to the liver was detected in 96 out of 1,825 patients with gastric cancer treated at our department from April 1980 to March 1990, and was respectively found to be synchronous and metachronous in 63 and 33 of the 96 patients. We compared survival durations among these 96 patients according to synchronous or metachronous metastasis by dividing them into the intermittent intra-arterial chemotherapy (FAM) group (18 patients) and non-intra-arterial chemotherapy group (78 patients). In the comparison between the intra-arterial and non-intra-arterial groups, the survival duration was determined to be significantly longer in the intra-arterial group by Wilcoxon generalized test and Cox-Mantel test (p less than 0.01). Among the patients with synchronous metastasis, a significantly longer survival duration was also observed in the intra-arterial group (p less than 0.01). The direct effect of intra-arterial chemotherapy through CT was seen in 56% of the patients in the intra-arterial group. These results indicated the usefulness of FAM hepatic infusion chemotherapy for the treatment of metastasis of gastric cancer to the liver. It is expected that therapeutic results will be much more improved by selecting more effective anticancer drugs in the future. PMID- 1888184 TI - [Study of intermittent intra-arterial infusion chemotherapy in liver metastases from squamous cell carcinoma]. AB - There are few reports about the methods, amounts, and kinds of dosage about intermittent intra-arterial chemotherapy of liver metastases from primal pathological type's squamous cell carcinoma. Because they are less than liver metastases from adenocarcinoma of colon or stomach. Although it is important of other factors about the operative method of primary focus and metastases of the other parts, it is possible that those cases obtained the good prognosis and protected liver failure, if those liver metastases could be controlled well. In our department from January 1987 to December 1989, 9 cases of inoperative liver metastases of squamous cell carcinoma (esophagus: 4 cases, larynx: 3 cases and cervix of uterus 2 cases) were treated of intra-arterial infusion chemotherapy of FAM (5Fu 500 mg/week, ADM 30 mg/4 weeks and MMC 4 mg/2 weeks) and CDDP methods (only CDDP 10 mg/week). Cases of esophagus carcinoma were treated with FAM method. On the CT-scan one of the cases showed the reduction rate of more than 50% and was a Progressive Response (PC), and the SCC tumor marker decreased in 2 cases. However, 2 other cases died of liver failure. Cases of larynx were treated with FAM and CDDP methods. However, on the CT-scan all of the cases showed No Change (NC) nor decrease in SCC. But thinking of prognosis FAM was better than CDDP. Cases of cervix of uterus were treated with the FAM and CDDP methods. FAM was not different than the CDDP in the prognosis and effect. PMID- 1888185 TI - [Adjuvant chemotherapy with vinblastine, adriamycin and UFT (VAU) for renal cell carcinoma]. AB - We tried adjuvant chemotherapy with vinblastine, adriamycin, and UFT on thirty one renal cell carcinoma patients in stage I, II or III to determine whether or not it might improve their survival rate. The patients were started on adjuvant chemotherapy with vinblastine 5 mg/m2 i.v. and adriamycin 30/m2 i.v. 7 to 14 days after surgery, and drugs were administered every 4 weeks for a total of 5 times. UFT was administered orally in a dose of 3 capsules (300 mg as tegafur) daily for 2 to 3 years. The postoperative period averaged 4 years and 2 months with a range of 2 years and 6 months to 7 years and 1 month. The 1-year survival rate for the 31 patients was 100%, and 3- and 5-year survival rates were 96%. These results were encouraging, compared to the 1-, 3-, and 5-year survival rates of 81%, 72% and 60% achieved in a series of 60 renal cell carcinoma patients in stage I, II or III without adjuvant chemotherapy. Side effects such as alopecia, gastrointestinal symptoms, and myelosuppression were observed, but all symptoms were so mild or transient that the treatment could be continued in the patients. PMID- 1888186 TI - [Notification of cancer in breast cancer patients]. AB - The notification of the name of disease is a premise for making the system of informed consent more complete in case of cancer treatment. In Japan, however, the notification of cancer can hardly be said to have an attained social consensus. Considering that the notification can ultimately improve patients quality of life (QOL), the breast cancer group of our department informs all breast cancer patients of their diseases in principle. This paper reports and discusses the results of a survey by questionnaire on the notification of cancer in 100 patients with breast cancer. The notification of cancer was received favorably in 83% of the patients. For those who answered, the explanation on the notification was convincing and it accounted for 81%. An examination of background factors of patients who had not been convinced revealed that many of them were suffered from advanced cancer. After the notification, a human relationship with the family and friends aggravated few of them and improved in 30% (family) and 18% (friends), respectively. The notification of cancer was thus suggested to contribute to the improvement of QOL. Although 83% well received the notification of their own diseases, only 21% were affirmative for the notification of cancer in case of a member of the family. We medical professionals should make a further effort not to make the notification of cancer the pronouncement death but to make it an aid for patients to live better. PMID- 1888187 TI - [A case of gastric cancer of Borrmann type IV complicated with carcinomatous peritonitis responding well to chemotherapy of tegafur only]. AB - A 46-year-old-male was admitted to our hospital with an unresectable stage of gastric cancer of Borrmann type IV with carcinomatous peritonitis. He was treated only with tegafur 900 mg/day. After 2 months' treatment, computed tomography showed ascites disappeared and a remarkable improvement was observed by barium meal study and endoscopic examination. The patient has survived for 12 months without any abdominal complaints and ascites since the beginning of treatment. Thus, this is a rare case responding well to chemotherapy of tegafur only. PMID- 1888188 TI - [Successful treatment of metastatic and refractory osteosarcoma by ifosfamide, carboplatin and vindesine: case report]. AB - A 13-year-old boy with unresectable pulmonary metastatic osteosarcoma, which was refractory to high dose methotrexate, adriamycin, cisplatin and combination of bleomycin, cyclophosphamide and actinomycin D, was treated by aggressive chemotherapy including the combination of ifosfamide (1 g/m2 x day 1-4), Carboplatin (100 mg/m2 x day 1-4) and Vindesine (4 mg/m2 x day 1). After 5 courses of the treatment, pulmonary metastasis regressed, respiratory symptoms resolved completely, and in this regimen no severe toxicity was observed. Thoracotomy for pulmonary metastatic osteosarcoma is an accepted treatment, but treatment for patients with unresectable disease has not been established. It is suggested that this regimen is relatively safe and very effective for refractory and unresectable osteosarcoma. PMID- 1888189 TI - [Intravaginal administration of CDDP for adenocarcinoma]. AB - Single vaginal administration of CDDP was done in a case of adenocarcinoma when relapse in the vaginal stump followed surgery for uterine corpus carcinoma. A tumor the size of a large fingertip in the vaginal stump was completely eliminated via 15-time (75 mg) CDDP vaginal administration, suggesting that this treatment was effective against adenocarcinoma. The only side effect over the whole body was slight pain developing in the external genitalia. PMID- 1888190 TI - [Conversion of CPT-11 into SN-38 in human tissues]. PMID- 1888191 TI - [Clinical treatment of MST-16 (Sobuzoxane) for malignant lymphoma]. PMID- 1888192 TI - [Basic study on hepatic artery chemoembolization using temperature-sensitive liposome in the treatment of hepatic tumor: animal experiment]. PMID- 1888193 TI - Diffuse pigmented villonodular synovitis: non-surgical management. PMID- 1888194 TI - Osteoarthritis in the elderly: clinical and radiological findings in 79 and 85 year olds. AB - The prevalence of joint complaints and clinical and radiological findings of osteoarthritis in wrist, hand, and knee joints was studied in representative population subsamples of 79 and 85 year olds. Joint complaints, clinical findings of osteoarthritis, and radiographic osteoarthritis were more common in women. Age related differences in the prevalence of osteoarthritis were not found. Although there was a correlation between clinical signs of osteoarthritis and radiographic osteoarthritis, clinical signs were often present without radiographic evidence and moderate and severe radiographic osteoarthritis was often present without clinical signs. PMID- 1888195 TI - Osteoarthritis of the hip and osteoporosis of the proximal femur. AB - A negative association has been reported between osteoarthritis and osteoporosis. There are, however, few population based data to support this association. In this study the bone density in the upper femur was compared with the presence and severity of hip osteoarthritis in 314 subjects undergoing radiography for non skeletal indications. There was a statistically significant negative association between the two disorders. This relation may reflect differences in the cause of these two major musculoskeletal conditions. PMID- 1888196 TI - Prevalence of antiphospholipid antibodies in patients with fetal loss. AB - The prevalence of antiphospholipid and antinuclear antibodies in 102 patients with at least three unexplained miscarriages before a gestational age of 12 weeks, or at least one intrauterine fetal death after 12 weeks, was investigated and compared with the prevalence in 102 normal pregnant controls. Six patients had a history of thrombosis and six had 'lupus-like' disease. Twenty one patients had anticardiolipin antibodies compared with 10 controls. Serum samples of nine patients and one control contained antinuclear antibodies. The lupus anticoagulant was present in the plasma of five patients with anticardiolipin antibodies. The influence of patient selection on the results was illustrated by the finding that antiphospholipid antibodies and antinuclear antibodies were mainly detected in patients with lupus-like disease or a history of thrombosis. When these patients were excluded there was no significant difference in the prevalence of anticardiolipin and antinuclear antibodies between patients and controls. Therefore, in the absence of lupus-like disease or a history of thrombosis, screening for antiphospholipid antibodies in patients with adverse pregnancy outcomes seems not to be indicated. PMID- 1888197 TI - Evidence for a promoter of urate crystal formation in gouty synovial fluid. AB - The effect of serum and synovial fluid obtained from six healthy subjects and from 12 patients with gout, six with rheumatoid arthritis and 18 with calcium pyrophosphate dihydrate arthropathy (CPPD) on the rate of in vitro urate crystal formation was measured. Gouty and normal serum produced similar results. Gouty synovial fluids promoted urate crystal formation significantly more than did rheumatoid or CPPD fluids. The promotion of urate crystal formation by gouty synovial fluid was not due to native urate crystals nor to an effect on the level of urate supersaturation. The development of gout in some, but not other, hyperuricaemic subjects may relate to the presence of promoters (or relative lack of inhibitors) of urate crystal formation in the group who develop gout. PMID- 1888198 TI - High molecular weight glycosaminoglycans in AA type amyloid fibril extracts from human liver. AB - Glycosaminoglycans have previously been identified in extracts of AA type hepatic amyloid fibril from a patient with amyloidosis associated with juvenile rheumatoid arthritis. The macromolecular properties of these polysaccharides are described here in more detail. By gel filtration and ion exchange chromatography glycosaminoglycans in the form of high molecular weight free chains were shown to coisolate with water extracted amyloid fibrils. About 60% of these were characterised as galactosamines (chondroitin sulphate/dermatan sulphate), whereas the remaining 40% consisted of N-sulphated glucosamines (heparin/heparan sulphate). The amyloid associated glycosaminoglycans were not part of intact proteoglycans in the fibril extracts. PMID- 1888199 TI - In vitro platelet aggregability studies: lack of evidence for platelet hyperactivity in systemic sclerosis. AB - Systemic sclerosis is characterised by vascular endothelial damage. Platelets adhering to the exposed subendothelium may contribute to the inflammatory changes found in the vessel wall. Increased in vitro platelet aggregability in systemic sclerosis has been reported. In vitro platelet aggregation of platelet rich plasma obtained from patients with systemic sclerosis (CREST (calcinosis, Raynaud's phenomenon oesophageal dysmotility, sclerodactyly, telangiectasia) variant) and from controls matched for age and sex was compared. Collagen, ADP, and platelet activating factor were used as aggregating agents. The actions of a platelet activating factor antagonist, BN52063, were also examined. Each agonist caused dose dependent platelet aggregation; there was no difference in either rate of primary aggregation or maximum percentage aggregation between platelets derived from patients with systemic sclerosis and from the control group (analysis of variance). BN52063 was shown to be a dose dependent, competitive antagonist of platelet aggregation induced by platelet activating factor; there was no difference in its action on platelets derived from patients with systemic sclerosis or controls. These results do not support the hypothesis that platelets from patients with systemic sclerosis are hyperactive and may explain the disappointing results obtained with antiplatelet drugs in systemic sclerosis. PMID- 1888200 TI - Clinical and biological characteristics of Ureaplasma urealyticum induced polyarthritis in a patient with common variable hypogammaglobulinaemia. AB - Persistent infectious polyarthritis caused by Ureaplasma urealyticum in a patient with common variable hypogammaglobulinaemia is described. The patient developed a symmetrical, destructive polyarthritis and tenosynovitis associated with a markedly depressed synovial fluid glucose concentration and characteristic soft tissue abscesses. The ureaplasma organism developed resistance to multiple antibiotics and persisted for five years. The organism was identified repeatedly in many joints by culture, confirmed by DNA hybridisation, and mycoplasma-like structures were shown in synovial tissues by electron microscopy. PMID- 1888201 TI - Breast vasculitis in association with breast gigantism in a pregnant patient with systemic lupus erythematosus. AB - A 24 year old woman with systemic lupus erythematosus (SLE) developed widespread necrotic skin ulceration and gigantism of both breasts during an exacerbation of SLE in the last trimester of her second pregnancy. Over the remainder of the pregnancy the ulceration was only controlled by high dose corticosteroids. After parturition, however, it was possible to reduce the steroid dose without recurrence of the ulceration. PMID- 1888202 TI - Interleukin 2 production in a family with systemic lupus erythematosus and a C4Q0 heterozygous inheritance. AB - Interleukin 2 production was studied in a family with systemic lupus erythematosus (SLE) and a C4Q0 heterozygous inheritance. Autoimmune manifestations seemed to be associated with the HLA haplotype containing the C4Q0 allele, which was shared by all four ill family members. Concentrations of interleukin 2, however, did not associate either with the haplotype or with the clinical or serological manifestations, as diminished concentrations of interleukin 2 were found in only two subjects with SLE. Thus the defect in this family seemed to be acquired rather than genetically conditioned. PMID- 1888203 TI - Measurement of haematological indices of chronic rheumatic disease with two newer generation automated systems, the H1 and H6000 (Technicon). AB - Two automated counters, the H1 (Technicon) and the H6000 (Technicon), which count 10,000 cells per sample, were compared and used to examine the clinical relevance of the additional haematological information now provided to the rheumatologist in three groups of patients--38 with rheumatoid arthritis (RA), 41 with ankylosing spondylitis (AS), and 35 with systemic lupus erythematosus (SLE). The two machines agreed in their estimations of the main indices (haemoglobin, red blood cell count, and white blood cell count), but estimations of platelet count and volume were significantly lower on the H6000 machine, as were mean cell haemoglobin and monocyte count, whereas packed cell volume and red cell distribution width were higher. As expected, both machines identified pancytopenia among the group with SLE, while low haemoglobin and high platelet count were found particularly among patients with RA and AS respectively. Additional information available from these counters showed marked variability in red cell size in SLE, and also of haemoglobin content, which is only measured on the newer H1 machine. Flags for microcythaemia, anisochromasis, and white cell noise (usually due to nucleated red cells) were all more common in SLE. Interpretation of results was complicated by the inevitable difference in age and sex distribution among the disease groups, and identification of active disease was also limited by the effect of drugs. In conclusion, the increasingly widespread use of automated counters as part of the routine haematological service may provide the rheumatologist with useful information, but, as always, care should be taken in the interpretation of indices in patients receiving non steroidal or second line agents, and also in extrapolating results from one machine to another when they are updated or when patients are monitored at more than one centre. PMID- 1888204 TI - Haemophilic arthritis. PMID- 1888205 TI - The ship and the eye. PMID- 1888206 TI - Observations and reflections on the immature stages of Onchocerca volvulus in the human host. AB - Knowledge of the morphology, migrations and development rates of the L3, L4 and prepubertal L5 stages of Onchocerca volvulus in the vertebrate host is an essential prerequisite to work vaccine development of chemoprophylaxis. After a brief review of the scanty literature available on this subject a description is given of two immature worms, one male and one female, found in an O. volvulus nodule from Guatemala. The male, which measured 12 mm x 40 micron(s), had fine regular transverse cuticular annulations, two prominent spicules, and an undifferentiated testis. The female, which measured 20 mm x 40 micron(s), had not yet developed cuticular ridges but showed a vulva, gut, and two rudimentary genital tracts. It is thought that these worms may have been six to 12 weeks old. The likely course of the early development of O. volvulus in the vertebrate host is discussed, based on analogy with O. lienalis in cattle; and some of the factors to be taken into account when pursuing the search for O. volvulus immatures are described. PMID- 1888208 TI - Observations on third-stage larvae and adults of Litomosoides carinii (Nematoda: Filarioidea) by scanning and transmission electron microscopy. AB - The morphology of the body wall of the infective third-stage larvae and adults of Litomosoides carinii was studied by scanning and transmission electron microscopy. The mouth of both stages is surrounded by four inner papillae and two outer papillae; a pair of amphidial glands open laterally between the inner papillae. Female larvae and adults have two lateral caudal papillae; male larvae have a single ventral one, and adult males have two ventro-lateral lines of caudal papillae. The larval cuticle is two-layered, with fibres in the inner layer, whereas the adult cuticle has four layers apparently traversed by channels. Except for the chordal regions, larvae and adults both have an exceptionally thin hypodermis which is separated from both the cuticle and the underlying muscle cells by highly-convoluted membranes. The dorsal and ventral hypodermal chords contain nervous tissue, whereas the lateral hypodermis contains mainly mitochondria, golgi and micro-organisms. The muscle cells of larvae and adults contain thick and thin myofilaments arranged parallel to the long axis of the worms. In larvae each section has nine to 12 muscle cells, each of which has an inner non-sarcoplasmic zone containing the nucleus. The muscle cells of adult worms, although fewer in number, are more complex, and those of male worms in particular have lamellae which are deeply invaginated to form dense rectangular bands. Glycogen and lipid droplets are absent from larval muscle cells, whereas they are present in those of adult worms. PMID- 1888207 TI - The Tsetse Research Laboratory. AB - The Tsetse Research Laboratory in Bristol was opened in December 1962, with the initial objective of developing techniques for rearing tsetse flies on a large scale outside Africa. Its work has, however, extended greatly since then. This article highlights the research undertaken at the Laboratory, not only on the breeding of tsetse flies but also on various aspects of their biology and control. PMID- 1888209 TI - Filariasis in Ceylon then (1961) and in Sri Lanka now (1990-30 years on). AB - The changes in the prevalence and distribution of bancroftian filariasis in Ceylon/Sri Lanka since Professor Kershaw's visit in 1961 show that the infection has spread over a wider area, although the microfilaria rates have decreased. New information is available on the vector, Culex quinquefasciatus, and more details are available on the animal filariae and their vectors. Dirofilaria repens infection of dogs is now a proven zoonosis in the country. PMID- 1888211 TI - The vector host link in filariasis. AB - Only a minority of microfilariae taken up by the appropriate vector develop to the infestive stage, and the distribution of the resulting third-stage larvae in the vector population is overdispersed. The larvae which reach the final host at first stimulate an immune defence reaction, but this is later suppressed. The importance of these factors in the life cycles of vector-borne parasites is considered. PMID- 1888210 TI - Experimental chemotherapy of lymphatic filariasis. A review. AB - An intense global collaborative effort under the leadership of the Steering Committee of the Filariasis Scientific Working Group of the Tropical Diseases Research Programme, World Health Organization, has brought together researchers, pharmaceutical chemists and clinicians in the development and search for antifilarial compounds which are more effective and more convenient to administer than diethylcarbamazine citrate, the current drug of choice for lymphatic filariasis. The Brugia spp.-rodent model has been used extensively for the primary screening and B. pahangi infections in the dog or cat for the secondary screening, of potential filaricides. Recently, the leaf-monkey (Presbytis spp.) infected with subperiodic B. malayi or Wuchereria kalimantani has been used for the tertiary evaluation and pharmacokinetic studies of compounds which have shown effectiveness in the primary and secondary screens. Both P. cristata and P. melalophos are extremely susceptible to subperiodic B. malayi infection, but the former is a better host as a higher peak microfilaremia and adult worm recovery rate were obtained. Although more than 30 potential filaricides have been evaluated in the tertiary screen, only a few compounds have shown some promise against lymphatic filariasis. CGP 20376, a 5-methoxyl-6-dithiocarbamic-S-(2 carboxy-ethyl) ester derivative of benzothiazole, had complete adulticidal and microfilaricidal activities against the parasite at a single oral dose of 20 mg kg-1. However, as the compound or its metabolites caused hepatotoxicity, its clinical use in the present formulation is not recommended.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1888212 TI - Mosquito host influences on development of filariae. AB - A brief review is presented of the literature relating to factors which limit the capacity of filariae to develop in mosquitoes, with particular emphasis on immune mechanisms. Most insects respond to bacterial infection by the production of potent antibacterial proteins, but little is known of this aspect of the immune response in mosquitoes or of the possible influence of immune proteins on the fate of filarial infections in mosquitoes. A summary account is given of recent experiments with the mosquito Aedes aegypti which involve passive transfer of immune haemolymph together with its in vitro assay and SDS-PAGE examination for induced proteins. These experiments demonstrate the production, in response to inoculation with Brugia pahangi, Escherichia coli, and various components of microbial cell walls, of haemolymph factors which are protective against filarial infection. It remains to be seen whether mosquitoes can produce a specific protective response to infection with eukaryotic organisms such as filaria that is distinctive from that mobilized against bacteria. PMID- 1888213 TI - The New World screw-worm fly in north Africa. AB - The course of the North African outbreak of New World screw-worm myiasis (Cochliomyia hominivorax) since its discovery in 1988 is described. Chemical and biological control measures are reviewed, including the current progress of the 'sterile male' (SIT) eradication programme. PMID- 1888214 TI - Freshwater crabs and Simulium neavei in east Africa. III. Morphological variation in Potamonautes loveni (Decapoda: Potamidae). AB - Potamonautes loveni (Colosi) is the valid name for the species also described as P. granviki, P. harvardi and P. loveni longimerus, and incorrectly identified as P. berardi berardi. Potamonautes jeanelli and P. idjwiensis may be allied to P. loveni, but are geographically separated and show sufficient morphological distinction not to be considered conspecific. Potamonautes loveni occurs in the upper reaches of rivers on the highlands of western Kenya and eastern Uganda. Its replacement by other species, principally P. niloticus, at lower altitudes is probably determined by the temperature range of the water. Potamonautes loveni has been observed to coexist with P. niloticus within the range of altitude 1280 1950 m. Distinct forms of P. loveni, differing in colour, size and the expression of the post-frontal crest, occur on the western side of Mt. Elgon and in the former ochocerciasis foci of Kenya. Hybridization is evident in populations from between these areas. Morphological divergence within P. loveni may be the result of past climatic change. Periods of generally lower temperature have been accompanied by increased aridity and reduction of forest cover. It is suggested that these conditions are such as to promote a disjunct distribution of P. loveni, and in particular the isolation of the Mt. Elgon population. PMID- 1888215 TI - The human parasite fauna: towards an analysis and interpretation. AB - A breakdown of the human parasite fauna shows approximately 270 species, with almost equal numbers of nematodes, flukes and protozoa and smaller numbers of arthropods and tapeworms. More than 70% are 'adventitious' species for which man is an incidental host. Only 16% are 'core' species, dependent on man for their survival. For 26% man is the usual source of human infection, and for 51% the source is other mammals. A sequence is illustrated showing how parasites may arrive by the host-transfer or co-evolutionary pathways. Adventitious parasites have a narrower geographical range than core species. The richest representation of the major species is in the Aethiopian Zoogeographical Region and the poorest is in the Australasian. Some 14 pairs of closely related forms occur in the main fauna. Some implications of this analysis with respect to man's early history are discussed speculatively. PMID- 1888216 TI - Elusive trypanosomes. AB - Professor Kershaw's encouragement of the development of anion-exchange separation of African trypanosomes from blood led to two decades of activity when, for the first time, considerable progress was made in the intrinsic characterization of these parasites. Such characterization depended on establishing high infections in laboratory rodents. However, the collection of samples from the field was restricted by the failure of certain trypanosomes either to infect, or to multiply adequately in, rodents. More recently, in vitro culture has come to play an increasingly important role in producing material. By obtaining procyclic forms directly from wild tsetse flies, or by transforming low numbers of bloodstream forms in field samples to the procyclic phase in experimental tsetse, trypanosomes of poor or nil infectivity to rodents were readily cultured in the large amounts required for biochemical characterization. A number of specimens of a new kind of Nannomonas, of Trypanosoma simiae, of T. grayi, and of an antigenically distinct T. brucei gambiense were found. Evidence is presented that many other kinds of trypanosome may be eluding isolation by their inability to infect rodents. PMID- 1888217 TI - Perspectives in research on and control of African trypanosomiasis. AB - African trypanosomiasis affects both man and his domestic animals, and is fatal if untreated. The risk of epidemics makes the disease a major public health problem in 36 sub-Saharan African countries, where some 50 million people are at risk of contracting the disease. Continued suppression of the disease through medical surveillance is indispensable to prevent epidemics which are difficult and costly to control. Recent epidemics and flare-ups have occurred in certain countries due to breakdown in medical surveillance occasioned by political, social and economic factors. The development of new tools through research over the last decade has improved the diagnosis of patients and vector control. The development of eflornithine (DFMO) for the treatment of gambiense sleeping sickness is a major breakthrough in view of its safety compared with current treatment alternatives, and it has been nicknamed the 'resurrection drug'. In spite of these achievements, however, there is no radical solution to the problem of sleeping sickness. The use by the endemic countries of improved tools for disease control depends upon the availability of resources from national, bilateral and multilateral sources, and commitment of the countries concerned. PMID- 1888218 TI - Lipid peroxidation as a component in trypanocidal drug action. AB - A representative range of trypanocides was examined for ability to induce lipid peroxidation in Trypanosoma rhodesiense in vitro. Because of drug interference, thiobarbituric acid (TBA) chromogen production and diene conjugation U.V. absorbance assay methods were less satisfactory that GLC analysis of polyenoic fatty acid loss. Docosohexanoic acid (22:6) content was specifically reduced to a highly significant degree by treatment with Ethidium or the lipid-soluble 4 demethoxydaunorubicin. PMID- 1888219 TI - Comparison of Trypanosoma grayi-like isolates from west and east Africa. AB - Three flagellates recently isolated from the hindguts of tsetse flies in West Africa were compared with a previously described T. grayi-like trypanosome isolated in East Africa. In media with Microtus agrestis feeder layer cells, the flagellates developed into bloodstream-like trypomastigotes, which resembled the description of T. grayi from the blood of crocodiles. The results of isoenzyme electrophoresis suggest that the isolates are T. grayi-like trypanosomes, and that some variation exists between the West and East African stocks of these reptile trypanosomes. PMID- 1888220 TI - The chemotherapy of rodent malaria. XLVI. Reversal of mefloquine resistance in rodent Plasmodium. AB - Multiple drug resistance in Plasmodium falciparum is already showing evidence of extending to mefloquine, which at present is one of the few alternative antimalarials for the prevention or treatment of infection with such parasites. Neither verapamil nor cyproheptadine, which reverse chloroquine (CQ) resistance in P. falciparum and in rodent malaria parasites, reverse resistance to mefloquine (MEF) in the MEF-resistant NS/1100 line of P. yoelii ssp. NS. On the other hand, such resistance is clearly reversed when mefloquine is administered to infected mice together with penfluridol. PMID- 1888221 TI - The growth and development of Echinococcus granulosus of sheep origin in dogs and foxes in Britain. AB - Four separate experiments were carried out by dosing dogs (Beagles and Border collies) and red foxes with protoscoleces obtained from hydatid cysts in sheep from mid-Wales. The dogs and foxes were killed at intervals over a period from 34 180 days after infection and the intestines were examined for Echinococcus granulosus. Border collie dogs were efficient hosts in that large numbers of worms developed, with gravid segments present by 55 days after infection; but Beagle dogs were poor hosts in that only small numbers of immature worms developed. Foxes were poor hosts in that few or no worms developed, but gravid segments were seen in three of 29 foxes. The worms showed morphological features similar to the 'sheep' rather than the 'horse' strain. PMID- 1888222 TI - The epidemiology of Echinococcus granulosus in the U.K. VIII. The structure of adult colonies of E.g. equinus say in farm dogs in Wales. AB - The status of Echinococcus granulosus equinus in farm dogs was examined in two valleys in South Powys, Wales. In one valley 76% of the dogs examined were infected, and there was at least one infected dog on every farm except one. In the second valley 49% of the dogs were infected. The structure of natural adult colonies of Echinococcus is described, and the population dynamics of the parasite in the U.K. is discussed. Every colony in the dogs, excepting the very smallest and the very youngest, consists of parasites at several stages of development. Most colonies comprise less than 20 worms. Colony density is greatest about the second or third eighth of the total length of the small intestine. The general characteristics of a colony (other than number) are reflected in the characteristics of the group of worms 'resident' in each successive eighth of the small intestine. Neither the age nor the sex of the host has any obvious effect on the incidence or the size of the colony, its development, or the ultimate infectivity of the colony. The parasites continue to grow throughout life, and growth may be largely independent of the worms' development. As a result, their length is very variable. The number of eggs in each gravid proglottid varies considerably, from 12-1626. All the evidence available and derived from the study of natural populations confirms that E. granulosus is an obligate self-fertilizing hermaphrodite, and that serial development of gravid proglottids does not occur. PMID- 1888223 TI - Membrane transport of amino acid enantiomers in protoscoleces of Echinococcus granulosus (Cestoda). AB - Protoscoleces of Echinococcus granulosus absorb both L- and D-alanine. Concentration ratios exceed 1 with values for D-alanine exceeding those for the L isomer, suggesting that both are absorbed by active mechanisms. Uptake of both isomers involves both diffusion and carrier-mediated components. Values for the diffusion component (Kd) for L- and D-alanine were 0.21 and 0.38 nmol mg-1 protein/1.5 min mM-1 respectively, and values for Kt, the transport constants, 0.17 mM and 0.21 mM respectively. Uptake of both isomers was inhibited competitively by a number of other amino acids. PMID- 1888224 TI - Human onchocerciasis: notes on the history, the parasite and the life cycle. PMID- 1888225 TI - The conquest of 'river blindness'. AB - Studies carried out at the WHO/OCP Onchocerciasis Chemotherapeutic Centre in Tamale, Ghana, are reported, culminating in the clinical trials of ivermectin (Mectizan), which has revolutionized our approach to the treatment of the disease. It is concluded that the conquest of 'river blindness' is an eminently achievable goal. PMID- 1888226 TI - Protective effect of (4R)-hexahydro-7,7-dimethyl-6-oxo-1,2,5-dithiazocine-4 carboxylic acid (SA3443), a novel cyclic disulfide, on immunologically induced liver injuries in mice. AB - The effects of (4R)-hexahydro-7,7-dimethyl-6-oxo-1,2,5-dithiazocine-4- carboxylic acid (SA3443), a novel cyclic disulfide, on new immunological liver injury models were investigated. The first liver injury model included a single injection of rabbit anti-basic liver protein antibody into DBA/2 mice. Serum transaminase activities showed a dose-dependent increase 42 hr after the antibody treatment. SA3443 significantly inhibited the elevation of serum transaminase activity and the histopathological changes of the liver in antibody-treated mice at doses of 100 to 300 mg/kg, p.o. The second hepatic failure model was based on an injection of lipopolysaccharide into BALB/c mice which had been previously treated with heat-killed Propionibacterium acnes (P. acnes). SA3443 reduced the lethal acute hepatic failure at doses of 100 to 300 mg/kg. Moreover, a distinct increase in lymphocyte-activating factor activity was detected in the supernatant of the culture medium of the liver macrophage/Kupffer cells isolated from the rat treated with P. acnes. SA3443, at 10(-6) to 10(-4) M, suppressed the release of the lymphocyte-activating factor activity from liver macrophage/Kupffer cells. These results suggest that SA3443 provides considerable protection against immunological liver injuries, and that the efficacy of SA3443 might be partially related to an inhibition of the increase in lymphocyte-activating factor activity. PMID- 1888227 TI - Effect of activated charcoal on the disposition of sulphadoxine. AB - Studies were conducted to examine the effect of activated charcoal on the disposition kinetics of sulphadoxine after Fansidar administration. Activated charcoal caused a significant reduction in ka, half-life and AUC0-48hr from 1.4 to 0.7 hr, 256 to 117 hr and 2533 to 1346 mg/l/hr, respectively. Activated charcoal absorbed sulphadoxine effectively in vitro. Sulphadoxine, at a simulated highly toxic dose of 5 mg/ml, showed adsorption percentages of 23.06, 28.66, 41.24, 64 and 100 to amounts of activated charcoal of 12.5, 25, 50, 100 and 250 mg, respectively. The results show that activated charcoal effectively adsorbs sulphadoxine both in vitro and in vivo. PMID- 1888228 TI - Pharmacological studies of lappaconitine: supraspinal-spinal interaction in antinociception. AB - Changes in lappaconitine levels in blood, brain and spinal cord following subcutaneous (s.c.) injection were correlated with the analgesic activity at intervals up to 90 minutes after injection. In the mouse, intracerebroventricular (i.c.v.) and intrathecal (i.t.) injections of amounts corresponding to ED50 values in the tail pinch method (i.c.v.: 2333 ng/mouse; i.t.: 1127 ng/mouse) gave peak lappaconitine levels of 1300 ng/g brain and 761 ng/g spinal cord, respectively. However, injection of lappaconitine at ED50 by the s.c. route (7 mg/kg) gave lower peak lappaconitine levels of 320 ng/g brain and 214 ng/g spinal cord. The responses to i.c.v., i.t. and combined i.c.v. plus i.t. administration of lappaconitine were evaluated by the determination of ED50 values, which were plotted as an isobologram. The experimental point is not significantly different from the theoretical additive ED50 point. When a dose equal to the experimental additive ED50 value (i.c.v., i.t. = 620, 413 ng/mouse) was injected, peak lappaconitine levels reached 344 ng/g brain and 241 ng/g spinal cord. Thus, the equianalgesic doses of lappaconitine (ED50 by the s.c. route and additive ED50 by the i.c.v. plus i.t. route) gave closely similar concentrations of the drug in brain and spinal cord. These results indicate that a simultaneous action of lappaconitine on supraspinal and spinal sites is likely to be important for the analgesia produced by systemically administered lappaconitine. PMID- 1888229 TI - Cholinergic modulation of spatial learning in mice in a Morris-type water maze. AB - Injection of the centrally active muscarinic antagonist scopolamine i.p. 20 min pre-test at 3 mg/kg but not at 1 mg/kg, impaired spatial learning of a Morris type water maze adapted for mice. Both doses caused hyperactivity. D-amphetamine (3 mg/kg, i.p.), which also caused hyperactivity, did not impair spatial learning nor did methylscopolamine (3 mg/kg, i.p.). In a cued version of the water maze, apart from a temporary disturbance on day 1, scopolamine (3 mg/kg) and control groups behaved similarly, indicating that scopolamine-induced place learning deficits are not due to changes in swimming ability, motivation or ability to use proximal cues. Physostigmine (0.1 and 0.2 mg/kg, i.p.) and oxotremorine (0.02 mg/kg but not 0.01 mg/kg, i.p.) antagonized the deficits in the swimming maze. Neither drug affected the scopolamine hyperactivity despite causing hypoactivity per se. In contrast, the peripherally acting cholinergic drug neostigmine was inactive against scopolamine in either test at 0.1 mg/kg. THA (2-8 mg/kg, i.p.), RS86 (0.25-1 mg/kg, i.p.) and nicotine (1 and 3 mg/kg, i.p.) were also unable to antagonize the scopolamine effect. These studies show that scopolamine disrupts acquisition of spatial rather than cued learning in mice in a Morris-type water maze and that this effect appears to be mediated centrally and can be dissociated from drug-induced hyperactivity. Moreover, this deficit can be reversed with certain cholinergic agents. PMID- 1888230 TI - Regional vasodilating effects of spirapril diacid and enalapril diacid in anesthetized dogs. AB - The acute regional hemodynamic effects of spirapril diacid, a novel nonsulfhydryl angiotensin-converting enzyme inhibitor, and enalapril diacid at an equidepressor dose were examined in anesthetized dogs by simultaneously measuring renal, coronary, vertebral arterial and aortic blood flow. Spirapril diacid (30 micrograms/kg, i.v.) lowered aortic pressure and increased aortic and renal blood flow associated with no marked change in heart rate, myocardial contractility, vertebral and coronary blood flow in a similar manner to enalapril diacid (30 micrograms/kg, i.v.). Both inhibitors thus produced an increase in stroke volume and a decrease of the rate-pressure product. The decrease of renal vascular resistance after administration of both agents was greater than that in vertebral and coronary vascular beds. A relatively more prolonged renal vasodilatation and a shortened coronary vasodilatation were seen with spirapril diacid as compared with enalapril diacid, despite practically identical reductions in total peripheral resistance. Each of the drugs markedly inhibited the pressor and renal vasoconstrictor responses to angiotensin I. These results indicate that the two inhibitors exhibit a similar profile of regional differences in vasodilatory effects, although they might display different durations of regional vasodilatation. PMID- 1888231 TI - Comparison of the cardiovascular effects of amineptine with those of amitriptyline and imipramine in anaesthetized rats. AB - In this study, two tricyclic antidepressant drugs and amineptine, administered to anaesthetized rats by intravenous bolus injection, were compared with regard to their in vivo cardiovascular effects. Amitriptyline and imipramine decreased mean arterial blood pressure and heart rate and caused conduction and rhythm changes in ECG. Amineptine, on the other hand, increased mean arterial blood pressure and caused a transient reduction of heart rate only at doses higher than those of amitriptyline and imipramine, while producing no noticeable ECG effects, even at doses 8 times higher than for the two tricyclic antidepressant drugs. The results of this study imply that amineptine, which structurally resembles tricyclic antidepressant drugs in having three rings and a side chain, has, nevertheless, a pattern of cardiovascular effects differing from that of amitriptyline and imipramine. PMID- 1888232 TI - Cardiohemodynamic effect of a novel calcium antagonist, SD-3211, in the dog. AB - The cardiohemodynamic effects of SD-3211, a calcium antagonist possessing a unique structure, were studied in anesthetized open-chest dogs and in conscious dogs. SD-3211 (10-300 micrograms/kg, i.v.) increased coronary and vertebral artery blood flow dose-dependently while lowering blood pressure, indicating a vasodilatation of these arteries. SD-3211 caused a significant increase in heart rate at 10-100 micrograms/kg, but a significant decrease at 300 micrograms/kg. Left ventricular dp dtmax was dose-dependently decreased at the dose range examined, and the change was significant at 300 micrograms/kg. When compared with the cardiohemodynamic effects of diltiazem (10 300 micrograms/kg, i.v.) and nicardipine (1-30 micrograms/kg, i.v.), the selectivity of SD-3211 with regard to vasodilatation as compared to cardiac depression, manifested by a reduction in heart rate and myocardial contractility, was greater than that of diltiazem, but less than that of nicardipine. Furthermore, a comparative study of the effects of orally administered SD-3211 and diltiazem on blood pressure and atrioventricular conduction in conscious, normotensive dogs, demonstrated that SD-3211 had a more potent and long-lasting hypotensive effect, but a much weaker effect on atrioventricular conduction prolongation than diltiazem. Thus, these in vivo cardiohemodynamic studies show that SD-3211 possesses a tissue-selectivity for vasculature, respectively cardiac tissues, which is intermediate between diltiazem and nicardipine. PMID- 1888233 TI - Cardiovascular depressant effects of N-methyl- and N-isobutyl-1,2-diphenyl ethanolamines: elucidation of the mechanisms of action. AB - The cardiovascular effects of N-methyl-1,2-diphenyl ethanolamine (compound M) and N-isobutyl-1,2-diphenyl ethanolamine (compound E) were examined in anaesthetized rats and their effects were compared with those of verapamil and diltiazem. Administration of compound M (10-80 mumole/kg), compound E (2-16 mumole/kg), diltiazem (1.5-24 mumole/kg) or verapamil (1.25-10 mumole/kg) induced dose dependent decreases in arterial blood pressure and heart rate. The induced cardiovascular changes were not antagonized by chlorpheniramine, cimetidine or imidazole. Indomethacin antagonized the diltiazem-induced hypotension without any effect on that of compounds M and E. The effects of all compounds tested were antagonized by pretreatment of the rats with CaCl2 (1.2-2.4 mmole/kg). Furthermore, methylene blue significantly antagonized the compound E- and diltiazem-induced hypotension. Treatment of the animals with propranolol enhanced the compound M- and E-induced hypotension. Compounds M and E antagonized the NA induced increase in arterial blood pressure in a competitive manner. Compounds M and E seem to exert their cardiovascular effects via interference with the influx of extracellular Ca2+. Furthermore, compound E and diltiazem may act partially via activation of guanylyl cyclase. PMID- 1888234 TI - What every physician should know about the National Practitioner Data Bank. PMID- 1888235 TI - The prevention of tetanus in the elderly. AB - Tetanus is a rare disease in the United States, which predominantly affects the elderly and who have a lower prevalence of tetanus immunity compared with younger age groups. A large proportion of the elderly have not received primary immunization for tetanus and do not receive recommended tetanus booster immunizations. Although expert panels support immunization of all persons, without an upper age limit, physicians either are unaware of or do not act on recommendations to immunize the elderly. Improved education of physicians and patients, emphasizing a case-finding approach, may reduce the number of tetanus cases in the elderly. Studies are needed to find ways to improve tetanus immunity in the elderly. PMID- 1888236 TI - Adult chronic lead intoxication. A clinical review. AB - A stained-glass artisan with depression and a retired junkyard worker with congestive cardiomyopathy had increased mobilizable body burdens of lead by calcium ethylenediaminetetaacetic acid testing. Although both patients improved with several months of intramuscular chelation therapy, the efficacy of such therapy in chronic lead poisoning is controversial. Recognition of unusual manifestations of chronic lead poisoning may at least interrupt further exposure, even if specific therapy is not undertaken. PMID- 1888237 TI - A critical review of the evidence supporting a relationship between impaired fibrinolytic activity and venous thromboembolism. AB - We critically evaluated the evidence for an association between venous thromboembolism and impaired fibrinolytic activity, as determined by global tests of fibrinolytic activity or specific tests for tissue plasminogen activator and plasminogen activator inhibitor. A computer-assisted and manual search was performed to retrieve all articles that reported on fibrinolytic activity and venous thromboembolism. The strength of the evidence for an association was assessed by analysis of the design of individual studies with special attention directed to choice of controls and methods of diagnosis of venous thromboembolism. It is concluded that for patients with symptomatic thrombosis the published evidence does not prove an association between impaired fibrinolytic activity and increased risk of thrombosis. In contrast, for postoperative thrombosis there is good evidence for an association between impaired fibrinolytic activity measured either preoperatively or postoperatively and increased risk of postoperative thrombosis. Whether this association is causal or coincidental is unclear, since randomized clinical trials that used interventions to enhance fibrinolytic activity produced inconsistent results. PMID- 1888239 TI - Influenza vaccination. Are we doing better than we think? AB - Patients who were candidates for influenza vaccination seen in the primary care center of a community teaching hospital were studied to determine whether there is a differential immunization rate depending on risk level. The immunization rate was as follows: moderate risk group, 44%; high risk group, 59%; and very high risk group, 81%. The immunization rate was also closely associated with the frequency of clinic visits, ranging from 34% for those with low visit frequency to 73% for those with high visit frequency. The highest vaccination rates were thus found in the groups at highest risk for influenza-associated morbidity and mortality. Although influenza complication rates are lower in the healthy elderly, this group is so large that the public health impact of a low vaccination rate will be significant. The healthy elderly should be the special targets of future influenza vaccination campaigns. PMID- 1888238 TI - Marine oil capsule therapy for the treatment of hyperlipidemia. AB - Because marine oil capsules may vary widely in their content of omega-3 fatty acids, saturated fat, and cholesterol composition and, therefore, their biologic potency, we compared the lipid-lowering effects of three representative preparations in patients with different forms of hyperlipidemia. The ester and triglyceride forms of marine oil both effectively lowered triglyceride, but the response of low-density lipoprotein cholesterol was variable; it declined modestly in patients with hypercholesterolemia and was either unchanged or increased in those with hypertriglyceridemia. The saturated fat and cholesterol content of the marine oil preparation appeared to influence the low-density lipoprotein cholesterol response. Therefore, marine oil capsules are useful for lowering levels of very-low-density lipoprotein cholesterol, but the large dose required to achieve and sustain this effect (4.5 g of omega-3 fatty acids, or nine to 18 capsules daily) may limit long-term compliance. PMID- 1888240 TI - Microalbuminuria in clinical practice. AB - Albumin excretion rate measured by new immunoassays and semiquantitative tests is advocated as a means for early detection of diabetic nephropathy. We determined albumin excretion rate in 276 patients. Albumin excretion rate was normal in 66%, within the microalbuminuric range in 27%, and within the macroproteinuric range in 7%. Significant predictors of albumin excretion rate included presence of hypertension and glycosylated hemoglobin level in type I diabetes mellitus, and years since diagnosis in type II diabetes mellitus. A semiquantitative test was deemed to be of limited diagnostic value. We conclude that testing for early diabetic nephropathy in routine clinical practice gives valuable information and that determination by a quantitative immunoassay based on a single 24-hour urine sample is preferable. The optimal frequency of screening and the levels that determine progressive renal disease have yet to be established. PMID- 1888241 TI - Rickettsial meningitis and encephalitis. AB - Nine of 72 patients with scrub typhus and three of 137 with murine typhus presented with meningitis and/or encephalitis syndromes. Focal neurologic signs were rare, and cerebrospinal fluid profiles were similar to those of leptospirosis and viral and tuberculous meningitis. One patient had papilledema, and another had cerebellitis. Other major organ involvement (renal, liver, or lungs) occurred in five patients. One patient died and four spontaneously recovered, while the conditions of the rest responded well to either chloramphenicol or doxycycline. Scrub and murine typhus should be included in the differential diagnoses of aseptic meningitis and encephalitis in patients exposed to endemic areas, especially when accompanied by renal insufficiency and/or jaundice. They are treatable forms of virallike meningoencephalitis. PMID- 1888242 TI - Assessment of risk of overt nephropathy in diabetic patients from albumin excretion in untimed urine specimens. AB - The ability of an albumin-to-creatinine ratio, measured in a single untimed urine specimen, to indicate the likelihood of developing overt diabetic nephropathy was determined in 439 Pima Indians (134 men, 305 women) aged 25 years or older with non-insulin-dependent diabetes. During a mean follow-up period of 4.2 years, 59 (13%) of the subjects developed overt nephropathy, 47 (80%) of whom had albumin to-creatinine ratios of 30 mg/g or greater at baseline. Subjects with albumin-to creatinine ratios of 30 to 299 mg/g (a level of excretion often termed "microalbuminuria") had 9.2 times (95% confidence interval, 4.4 to 21.4) the incidence of overt nephropathy of those with ratios of less than 30 mg/g. Furthermore, the albumin-to-creatinine ratio remained a strong predictor of overt nephropathy even when controlled for age, sex, diabetes duration, mean blood pressure, and 2-hour postload plasma glucose concentration with a proportional hazards function analysis. Thus, an albumin-to-creatinine ratio measured in a single untimed urine specimen is an effective means of identifying diabetic subjects who are at risk of developing overt nephropathy that could replace the more traditional timed urine collections. PMID- 1888243 TI - Outpatient use of prescription sedative-hypnotic drugs in the United States, 1970 through 1989. AB - Data from two pharmaceutical marketing research databases, the National Prescription Audit and the National Disease and Therapeutic Index, were used to study outpatient use of prescription sedative-hypnotic drugs in the United States from 1970 through 1989. Retail pharmacies dispensed an estimated 62.5 million prescriptions for sedative-hypnotic drugs in 1970. This number declined by half to 31.6 million in 1978. This decline has continued, so that in 1989 there were 20.8 million dispensed prescriptions. From 1970 to 1989, barbiturate and nonbarbiturate-nonbenzodiazepine prescriptions decreased 24-fold and 18-fold, respectively, and benzodiazepine prescriptions increased 26-fold. By 1989, the ultrashort-acting benzodiazepine drug triazolam was the leading sedative hypnotic, with about 40% of the total sedative-hypnotic market in the 6 years since its marketing. Data also indicate shifts from longer to shorter acting, and from higher to lower dose, benzodiazepine prescriptions, increasing use of antidepressant drugs for insomnia, female predominance of use, and increasing use with age. PMID- 1888244 TI - Resistant hypertension in a tertiary care clinic. AB - STUDY OBJECTIVE: --To determine the prevalence of resistant hypertension in a tertiary care facility, the frequency of its various causes, and the results of treatment. DESIGN: --Review of clinic records of all patients seen for the first time between January 1, 1986, and December 31, 1988. METHODS: --Patients meeting criteria for resistant hypertension were examined for appropriateness of their medical regimen, presence of secondary causes of hypertension, noncompliance, interfering substances, drug interactions, office resistance (elevated blood pressure in the office only while receiving treatment), and other potential causes of resistance. RESULTS: --Of the 436 charts reviewed, 91 were those of patients who met criteria for resistant hypertension and were seen more than once. The most common cause was a suboptimal medical regimen (39 patients), followed by medication intolerance (13 patients), previously undiagnosed secondary hypertension (10 patients), noncompliance (nine patients), psychiatric causes (seven patients), office resistance (two patients), an interfering substance (two patients), and drug interaction (one patient). Blood pressure control, defined as diastolic blood pressure of 90 mm Hg or less and systolic blood pressure of 140 mm Hg or less for patients aged 50 years or less (less than or equal to 150 mm Hg for those aged 51 to 60 years and less than or equal to 160 mm Hg for those aged greater than 60 years), was achieved in 48 (53%) of those 91 patients. Another 10 had significant improvement in their blood pressure (greater than or equal to 15% decrease in diastolic blood pressure). Of patients whose blood pressure was controlled after they had been on a suboptimal regimen, the two most frequently used therapeutic strategies were to add (50%) or modify (24%) diuretic therapy or to add (50%) or increase the dose of (12%) a newer drug, either a calcium entry blocker or angiotensin-converting enzyme inhibitor. CONCLUSION: --We conclude that resistant hypertension is common in a tertiary care facility and that a suboptimal regimen is the most common reason. Furthermore, in the majority of these patients, the elevated blood pressures can be controlled or significantly improved. PMID- 1888245 TI - Air travel in patients with chronic obstructive pulmonary disease. AB - Air travel exposes patients with chronic obstructive pulmonary disease to the risk of severe hypoxemia. We sought to determine the frequency and outcome of airline travel in patients with chronic obstructive pulmonary disease. A cohort of 100 patients (76 men and 24 women; age 67 +/- 7 years [mean +/- SD]) with severe chronic pulmonary obstructive disease examined by means of spirometry (forced expiratory volume in the first second, 0.04 +/- 0.35 L), all military retirees, or their dependents, comprised the study population. Forty-four patients traveled by commercial air carrier over a 28-month interval, giving an annual frequency of 18.9% of these patients per year. The group that did not travel by air (n = 56) had a lower mean value for forced expiratory volume in the first second and greater prevalence of home oxygen use than did the group that did travel by air. Twelve of the travelers (27.3%) consulted a physician beforehand. Flights reached foreign destinations for 22.7% of patients. The median duration of the longest flight segment was 3 hours. A minority of patients (34.3%) occupied seats in the smoking sections of aircraft. A majority (56.8%) ambulated aboard the aircraft during flights. Eight patients (18.2%) reported transient symptoms during air travel. We conclude that patients with chronic obstructive pulmonary disease travel with appreciable frequency, often without medical consultation, and develop symptoms in some cases. PMID- 1888246 TI - Bacteremia in febrile patients. A clinical model for diagnosis. AB - Among 244 patients aged 18 to 98 years who were consecutively hospitalized in a department of internal medicine because of a febrile disease, 52 (21%) were bacteremic. On a logistic regression analysis, five variables known within 24 hours of admission were found to be associated both significantly and independently with bacteremia: low serum albumin level, low premorbid performance status, chills, renal failure, and an assumptive diagnosis of urinary tract infection on admission. The logistic model was used to divide patients into three groups. In group 1, the percentage of bacteremic patients was 5%, in group 2, 40%, and in group 3, 83%. The percentage of deaths in the three groups was 0%, 23%, and 50%, respectively. The model was validated in a second group of 257 patients. The percentage of bacteremia was 1% in group 1, 23% in group 2, and 65% in group 3. The death rate in three groups was 3%, 4%, and 35%, respectively. The accuracy of the attending physician in diagnosing bacteremia within 24 hours of hospitalization was compared with that of the model. Use of the model could have improved the diagnostic accuracy in 5% of the patients in group 1 and in 18% of patients in group 3. PMID- 1888247 TI - Iatrogenic renal disease. AB - We studied iatrogenic problems in nephrology by classifying all patients for nephrology consultation into nine presenting syndromes and seven etiologic groups. One hundred (2.2%) of all admissions were seen in nephrology consultation. Acute renal failure was the most common presenting syndrome, accounting for 59% of the consultations. Forty-one of the 100 consultations (1% of all admissions) had a renewal syndrome of iatrogenic origin. Of these 41 patients, 38 had acute renal failure and three had fluid and electrolyte problems. Twenty of the 41 patients had drug-induced problems. Eighteen of these patients were dehydrated, and in three patients, acute renal failure occurred after surgery. Of the 20 patients with iatrogenic renal problems caused by drugs, seven problems were antibiotic related, five were due to diuretics, four were due to nonsteroidal anti-inflammatory drugs, three were due to angiotensin-converting enzyme inhibitors, and one was from the use of contrast medium. The 41 patients with iatrogenic-related renal disease were older than the other 59 patients (61.8 vs 49.3 years). Iatrogenic renal disease developed in 1% of all patients admitted to a tertiary care hospital, and 12% of these patients died. The most common renal syndrome is acute renal failure, most often caused by nephrotoxic drugs. The incidence can probably be decreased by better monitoring of body weight and fluid balance to prevent dehydration and by the avoidance of nephrotoxic drugs. PMID- 1888248 TI - A randomized controlled trial of the effects of three antihypertensive agents on blood pressure control and quality of life in older women. AB - We conducted a multicenter, randomized, double-blind, parallel group trial to compare the impact of titrated doses of atenolol (50 to 100 mg once a day), enalapril (5 to 20 mg once a day), and diltiazem (sustained release) (60 to 180 mg twice a day) on blood pressure and quality of life in older hypertensive women. Two hundred forty-two patients were randomized. Dose titration was completed by week 4 after randomization, and the maintenance phase was completed at week 16. Diltiazem (sustained release) demonstrated greater diastolic blood pressure lowering at both weeks 8 and 16 by an intent-to-treat analysis. At week 16, diltiazem changed diastolic blood pressure -13.7 +/- 0.7 mm Hg compared with 10.8 +/- 1.1 mm Hg for atenolol, and -10.5 +/- 0.9 mm Hg for enalapril. Diltiazem also demonstrated greater lowering of systolic blood pressure at week 3, but these differences in systolic blood pressure had decreased by week 16. More patients were classified as treatment failures during the 16 weeks of the trial for atenolol (15%) than for diltiazem (2.5%), while the treatment failure rate was intermediate with enalapril (8%). Total rates of adverse events were equivalent across the three treatment arms. There were few significant differences in the impact of the three treatments on mean scores of quality-of life measures at week 16. There was a trend for atenolol to have somewhat worse quality-of-life scores, but none of these differences were statistically significant. In conclusion, all three treatment regimens were effective in lowering diastolic blood pressure without significant differences in rates of adverse events or deleterious effects on quality of life. PMID- 1888249 TI - Explicit criteria for determining inappropriate medication use in nursing home residents. UCLA Division of Geriatric Medicine. AB - Increasing attention is being paid to inappropriate medication use in nursing homes. However, criteria defining the appropriate or inappropriate use of medication in this setting are not readily available and are not uniform. We used a two-round survey, based on Delphi methods, with 13 nationally recognized experts to reach consensus on explicit criteria defining the inappropriate use of medications in a nursing home population. The criteria were designed to use pharmacy data with minimal additional clinical data so that they could be applied to chart review or computerized data sets. The 30 factors agreed on by this method identify inappropriate use of such commonly used categories of medications as sedative-hypnotics, antidepressants, antipsychotics, antihypertensives, nonsteroidal anti-inflammatory agents, oral hypoglycemics, analgesics, dementia treatments, platelet inhibitors, histamine2 blockers, antibiotics, decongestants, iron supplements, muscle relaxants, gastrointestinal antispasmodics, and antiemetics. These criteria may be useful for quality assurance review, health services research, and clinical practice guidelines. The method used to establish these criteria can be used to update and expand the guidelines in the future. PMID- 1888250 TI - Problems in the use of serologic tests for the diagnosis of Lyme disease. AB - Lyme disease can be reliably diagnosed in the presence of erythema migrans. When erythema migrans is absent, serologic tests are often used to confirm the diagnosis. To choose a test for our Lyme disease diagnostic center, serum samples were obtained from 34 patients and tested for antibodies to Borrelia burgdorferi. We evaluated five enzyme-linked immunosorbent assays from Stony Brook (NY) University Hospital, Cambridge Bioscience (Worcester, Mass), Hillcrest Biologicals (Cypress, Calif), Sigma Diagnostics (St Louis, Mo), and Zeus-Wampole Scientific Inc (Raritan, NJ) and two fluorescent antibody tests (3M [Diagnostic Systems Inc, Santa Clara, Calif] and FIAX [Whittaker M.A. Bioproducts Inc, Walkersville, Md]). A positive sample by any test was further analyzed by Western blot. Using the Centers for Disease Control (Atlanta, Ga) epidemiologic case definitions, patients were classified into those with clinical Lyme disease, patients not meeting the Centers for Disease Control definitions, and asymptomatic patients. Sensitivities of Lyme serologies varied from 13% to 73%, with Hillcrest showing the highest value and Sigma the lowest value. False positive test results were found in 0% to 27% of patients. Western blot analysis was positive in six of 15 patients with clinical Lyme disease. These results emphasize the need for better serologic testing for Lyme disease and underline their usefulness only as adjuncts in the clinical diagnosis of Lyme disease. PMID- 1888251 TI - Symptoms associated with tamoxifen treatment in postmenopausal women. AB - Adjuvant breast cancer therapy with tamoxifen is associated with greater disease free survival and possibly overall survival. Long-term treatment, possibly of indefinite duration, is being evaluated. Compliance with long-term therapy will depend largely on the nature and severity of tamoxifen's side effects. We evaluated the symptoms associated with tamoxifen therapy in 140 postmenopausal women with axillary node negative breast cancer in remission (mean years since menopause, 9.3) enrolled in a placebo-controlled, randomized toxicity study. Tamoxifen recipients reported moderated or severe vasomotor symptoms up to 17%, and gynecologic symptoms up to 4% more frequently than placebo subjects. Persistent vasomotor, gynecologic, or other major side effects were reported by 48% of tamoxifen recipients, and by 21% of placebo subjects. These carefully collected data suggest significant perceived symptom 'cost' of tamoxifen therapy in postmenopausal women, of a magnitude likely to compromise long-term compliance. PMID- 1888252 TI - Feasibility of universal screening mammography. Lessons from a community intervention. AB - It is estimated that 44,500 American women will die of breast cancer in 1991. The breast cancer screening guidelines of the American Cancer Society and the National Cancer Institute calling for annual mammography for all women older than 50 years have been endorsed by numerous professional groups. Third-party reimbursement for screening mammography is becoming more prevalent, and payment for screening mammography is now a Medicare benefit. Our studies, conducted as part of a National Cancer Institute grant to increase the routine use of screening mammography and clinical breast examination in women 50 to 75 years of age, have uncovered a number of significant barriers to the implementation of screening guidelines among women, primary care physicians, and providers of mammography services. These barriers, as well as methods to assure the quality of mammography, need to be addressed before universal screening is feasible. PMID- 1888253 TI - Clinical spectrum of sulfonylurea overdose and experience with diazoxide therapy. AB - We retrospectively reviewed our 10-year experience with the management of sulfonylurea overdose. There were 40 overdoses in 37 patients aged 1 to 78 years, with two deaths and one patient being left in a chronic vegetative state. Blood sugar levels ranged from normal to severe recalcitrant hypoglycemia. Maximal duration of recurrent hypoglycemia was 82 hours. In 21 of 31 patients with hypoglycemia, response to hypertonic glucose therapy was poor, resulting in recurrent hypoglycemia. Six of these patients were treated with intravenous diazoxide and had prompt correction. Overdose of sulfonylurea drugs may produce severe, protracted hypoglycemia poorly responsive to hypertonic glucose therapy. Treatment with diazoxide is rational and effective and may be lifesaving. PMID- 1888254 TI - Cushing's disease and cutaneous alternariosis. AB - Alternaria species are common plant pathogens, but a rare cause of human infection. We present a patient with cutaneous alternariosis that revealed a relapse of an old case of Cushing's disease. Immunosuppression following the excessive glucocorticoid production seemed to contribute to the development of dermatosis. We also present a review of the literature on the association of Cushing's disease and cutaneous alternariosis. Our case is unique because the ketoconazole therapy that we used was successful in the treatment of both diseases. PMID- 1888255 TI - Nifedipine GITS (gastrointestinal therapeutic system) bezoar. AB - In a patient with a gastroplasty, gastric outlet obstruction developed after the dosage of nifedipine GITS (gastrointestinal therapeutic system) was increased from 30 to 60 mg/d. The hard, insoluble shell for this extended-release tablet appears causative. PMID- 1888256 TI - Drug-induced fever due to diltiazem. AB - To our knowledge, drug-induced fever has not been reported with the use of diltiazem hydrochloride, a commonly prescribed calcium channel blocker. We describe a patient in whom this was the primary manifestation of drug hypersensitivity. A 67-year-old man was admitted for management of a diabetic foot ulcer. His hospital course was complicated by a non-Q-wave myocardial infarction, for which diltiazem was prescribed. On the seventh day of therapy, he experienced fever, with temperatures as high as 38.8 degrees C. Despite an extensive evaluation, which included a gallium scan, a technetium bone scan, and abdominal ultrasound, a source could not be found. On the 16th day of therapy, however, relative eosinophilia developed, and 2 days later a pruritic maculopapular rash appeared. Diltiazem therapy was discontinued, leading to resolution of fever within 48 hours. Drug-induced fever should be considered in patients who have unexplained high temperatures during diltiazem therapy. PMID- 1888257 TI - Gemfibrozil-induced myopathy. AB - Drug-induced myopathy has been reported with use of lovastatin, nicotinic acid, and clofibrate. A particularly severe form, often accompanied by rhabdomyolysis, has been reported with the use of lovastatin and gemfibrozil; however, as far as we know, no case has been documented with use of gemfibrozil alone. Herein, we report the first case (to our knowledge of gemfibrozil-induced myopathy, confirmed by drug rechallenge. PMID- 1888258 TI - Gender and lipids in coronary artery disease. PMID- 1888259 TI - Isoniazid prophylaxis for young adults. PMID- 1888260 TI - Cystocerebral syndrome: a possible explanation. PMID- 1888261 TI - [Asphyxia protracted after shaking trauma]. AB - A case of "shaken baby syndrome" (SBS) is reported. A 3 1/2 months old female baby has been found by his mother death in bed. The circumstances predicted a case of Sudden Infant Death Syndrome (SIDS), but the father, a disc-jockey, who had to look for the baby, had left a notice: "Gitti--i didn't want it, I don't know what had happened, I'm sorry!". The corpse of the baby had no external signs of violence. At the medicolegal examination we found small subarachnoidal and subdural hemorrhage from ruptured bridge veins and signs of prolonged asphyxia. Few hours later the father could be arrested. He told that he had shaken the baby, because she didn't stop crying. The infant lost conscious and he layed him down to the bed with his face below. Then he looked TV for at least a few minutes. After insufficient reanimation he had left the house. The court found the man to be guilty of fatal infant child abuse and convicted him to detention of 8 months. The main signs of SBS are discussed (subarachnoidal and subdural hemorrhage, intraretinal and periretinal hemorrhages, brain edema). Especially in the german speaking Europe many medical examiners are not familiar with this form of infant child abuse. PMID- 1888262 TI - [Casuistics of unusual death from loss of blood]. AB - 7 cases of unusual natural and unnatural death due to loss of blood are reported. The case reports show the important role of acute and chronic alcohol abuse in this context. They also demonstrate the problems of necropsy caused by the unusual and suspicious situation, in which the corpses are often found; even in cases of natural death sometimes the first aspect arouses the suspicion of a crime. PMID- 1888263 TI - [Ultrafiltration, an efficient method for purification of DNA from stains]. AB - Isolating DNA from stains all pollutions are extracted, too. Restriction of the DNA can be prevented. After phenol extraction the DNA had been ultrafiltered. Photometrically measurement and fingerprinting showed, that the disturbing substances are removed. PMID- 1888264 TI - Biochemical mechanism of caffeine tolerance. AB - Most of the biological actions of caffeine are possibly mediated through its antagonistic effects to adenosine. Adenosine activates an inhibitory GTP-binding protein (Gi). One of the physiological actions of Gi is the inhibition of cAMP formation. Caffeine overcomes this action thus leading to elevation of cAMP. Firing of neurons and the release of neurotransmitters is also inhibited by adenosine. Caffeine overcomes this effect, thus producing increased CNS-activity. During long term administration of caffeine many functions of the organism develop tolerance including cardiovascular and central nervous systems. Present evidence suggests that caffeine tolerance following continuous severe coffee ingestion is the response of the body against caffeine through the upregulation of adenosine receptors. PMID- 1888265 TI - Synthesis and antifungal activity of some new benzimidazole derivatives. AB - Synthesis and antifungal evaluation of 5-ethoxycarbonyl-2-(substituted-benzyl or phenoxymethyl)benzimidazoles are reported. Structures of the compounds were elucidated with IR-, 1H-NMR-, 13C-NMR-, mass-spectra and elemental analysis. Preliminary results show that none of the synthesized benzimidazole derivatives has antifungal activity at the concentration of 100 micrograms/ml against Candida parapsilosis, Candida stellatoidea, and Candida pseudotropicalis. PMID- 1888266 TI - [Ciprofibrate: erythrocyte partition coefficient and binding to serum protein]. AB - The in vitro binding of the lipid lowering agent Ciprofibrat (1) to different plasma protein fractions and its red blood-cell partition coefficient were investigated. The binding-rate to albumin and alpha-globulin is dose-dependent (first order kinetic) and amounts to about 95% for albumin and to 25% for alpha globulin. The affinity of 1 to beta- and gamma-globulin is non-specific and dose independent (average binding-rate 8% and 10%, respectively). 1 shows only a weak affinity to erythrocytes, therefore, the red blood-cell partition coefficient is 0.02. PMID- 1888267 TI - Platelet aggregation inhibiting and anticoagulant effects of oligoamines, XV: Antithrombotic effect of selected oligoamines in rats. AB - Oligoamines which exert antiplatelet and anticoagulant properties in vitro show as well antithrombotic effects in mesenteric arterioles and venoles of rats. The formation of thrombi in these vessels was induced by a laser beam and quantified by the thrombus formation index (TFI). The most potent compound RE 1492 already reduced the formation of thrombi after i.v. administration of 1 mg/kg significantly. After oral administration, however, only a minor effect even after a 200 mg/kg dose is observed. This suggests that the oligoamine was poorly absorbed from the gastrointestinal tract. The tricarbamate of RE 1492 (identical to RE 1492 C), however, was a suitable prodrug. Eight hours after a single oral dose of 10 mg/kg significant antithrombotic properties in arterioles and venules were seen. (TFI = 3.63 (A), 1.77 (V); control: 1.76 (A), 1.29 (V).) After p.o. application of 30 mg/kg RE 1492 C the onset of activity is after 2 h (TFI = 3.44/1.48). A maximum effect is reached after 4 h (TFI: 4.43/2.84) and maintained up to 24 h (TFI = 4.49/2.45). After 48 h the effect in arterioles is still significant (p less than 0.05, chi 2-test). The results obtained with five other carbamates (RE 2029 C, RE 1964 C, RE 2120 C, RE 2112 C, and RE 1981 C) 4 h after p.o. administration in general show a stronger effect in arterioles than in venules which is in the same range as in RE 1492 C. PMID- 1888268 TI - [5-Acyloxydioxolanones as prodrugs of non-steroidal anti-inflammatory agents. 1]. AB - The derivatissation of various acidic non-steroidal anti-inflammatory drugs to 5 acyloxy-1,3-dioxolan-4-ones is described. The synthesis of the title compounds is achieved by reaction of 5-bromo-1,3-dioxolan-4-ones with the salts of the carbonic acids. PMID- 1888269 TI - The influence of protein level in the diet on nitrogen content in the total, and in the gain of body mass of growing male rats. AB - The experiment was conducted on 364 male Wistar rats of which 74 were included into the "zero" group and the remaining 290 were divided into 5 experimental groups, corresponding to the dietary protein levels of 4, 5, 10, 15 and 20%. The protein source in the diet was skim milk powder. The animals were fed individually and ad libitum. The experiment was performed between the 21 and 66 days of life of the rats and during this period, the animals in each group were successively killed to determine the nitrogen content in the body. Between the N content in the body and the body mass of rats from "zero" group, the relationship N0/W0 was determined. In each experimental group, two relationships were determined: --final nitrogen against final body mass--Nf/Wf --gain of nitrogen against gain of body mass--delta N/delta W. The derivatives of both functions were used for calculation of the daily gains of nitrogen (delta Nd) 1. According to the relationship Nf/Wf there was a similar significant increase of nitrogen content in the body in all groups with increasing the body mass, according to bc = 1.0413. The percentage of nitrogen in the body increased significantly only at dietary protein levels over 10%. 2. The rate of nitrogen gain in the gain of body mass according to delta N magnitude of was relatively constant in all groups (bc = 1). Thus, N-% in delta W was also relatively constant. N-% in the body gain increased significantly only at dietary protein levels over 10%. 3. Differences in the gains of nitrogen, as calculated by the derivative dNf/dWf and by d delta N/d delta W, showed in the first line in low-protein groups (on 4 and 5% protein) due to the error of estimation of the initial-N according to the equation N0 magnitude of W0. The mean relative error of estimation the initial-N was +/- 3% but in groups on 4 and 5% protein it charged the gain of N with 9-12% in spite of excluding from the relationship delta N magnitude of delta W rats with delta W less than 10 g. 4. Only when delta N greater than or equal to 1.3 g and delta W greater than or equal to 43, the error of estimation of delta N, did not exceed 3%.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1888270 TI - Cellulose fermentation capacity of the hindgut and nitrogen turnover in the hindgut of sows as evaluated by oral and intracecal supply of purified cellulose. AB - Adult sows fed a constant amount of a basal diet received purified cellulose either orally at levels of 0 and 475 g/animal.d (Experiment 1) or intracecally at levels of 0, 285, 570 and 855 g/animal.d (Experiment 2). Each experiment consisted of subsequent periods of faeces and urine collection with the animals re-allocated to the treatments each time. With that, a total of 36 observations on each parameter was achieved. The faecal samples were analyzed for the contents of organic matter, cell wall carbohydrates and various nitrogen fractions such as bacterial N and undigested dietary N. Furthermore, N balance, urinary allantoin excretion and plasma urea concentrations were determined. In a preliminary study, the effects of freeze-drying and of shaking of the faecal samples as suspensions with water (in order to release bacteria from fibre) on content and composition of faecal nitrogen had turned out to be reproducible. Cellulose significantly enhanced faecal nitrogen loss whereas N retention was not affected due to the counteraction of urinary N loss. Plasma urea concentration reflected the situation with urinary N. The proportion of undigested dietary N and of water soluble protein in total faecal N was somewhat increased by cellulose at cost of the bacterial N proportion which accounted for about 72% of total N on average. Urinary allantoin did not respond to the higher bacterial activity in the hindgut in the presence of supplementary cellulose. Cellulose significantly decreased the apparent N digestibility by on average about 3 percentage units per 100 g of supplementary cellulose. True N digestibility was also reduced by cellulose but did not go below 95%. The supplementary cellulose was fermented in the hindgut at similar rates of on average about 60% regardless of the route of administration. The almost 100 g of native cellulose incorporated in the basal diets were lignified by about 20%, and that is why they were fermented at a rate of only about 30%. The rate of fermentation was only slightly decreasing with increasing amounts of supplementary cellulose, and a daily quantity of 564 g (11 g/W0.75) cellulose was fermented on average if the highest level of cellulose was provided. This was within a range exclusively reported for easily-fermentable carbohydrates but was achieved in the case of cellulose only at a consistently higher level of supply. The true efficiency of bacterial protein synthesis was 5.2 g bacterial protein/100 g supplementary cellulose on average. The apparent efficiency was 60% higher averaging 8.4 g bacterial protein/100 g further apparently fermented organic matter. PMID- 1888271 TI - [The energy metabolism of growing swine in the liveweight range of 10-50 kg. I. Study design, feed intake and digestibility]. AB - Studies of the energy metabolism at maintenance and growth levels after the feeding of rations with a crude protein content of 17-24% and 44-47% resp. were carried out with hybrid pigs of line 150 in the live weight range between 10 and approximately 50 kg. This paper gives information on the methods and the outlay of the experiment and presents results concerning feed intake, live weight development and digestibility. Feed intake increased on average with growing live weight by 30-35 g DM/kg live weight. Feed conversion ranged from 1.2 to 1.8 kg DM/kg live weight gain in the first period and from 2.3 to 3.2 kg DM/kg live weight gain in the last period. The digestibility of the energy in the rations with a crude protein content of between 17 and 24% averaged 80% and that of the rations with a crude protein content of 44-47% averaged 86%. In the course of ontogenetic development the digestibility increased up to about 30 kg LW. The influence of the nutritional level on the level of digestibility was unequal in the experiments. In one experiment a decrease (1% unit) and in two experiments an increase (1-3% units) of the digestibility after the feeding of growth level in contrast to maintenance level could be observed. The change of rations with a varying protein content did not result in an influence on the digestibility level in comparison with the constant feeding of one ration. PMID- 1888272 TI - [Purine and pyrimidine metabolites for the estimation of rumen metabolism: HPLC analysis in milk and blood plasma]. AB - In milk and blood plasma samples of 6 German Simmental and 12 German Black and White heifers it was investigated, whether purine and pyrimidine compounds are suitable indicators of the microbial protein synthesis in the rumen. Therefore the secreted quantities in milk and the concentration in blood plasma are correlated with energy intake. The results indicated significant correlation coefficients for both the secretion quantity of allantoin in milk (r = 0.942) and the concentration of allantoin in blood plasma (r = 0.694). Other investigated compounds appeared more suitable for evaluating the mammary gland metabolism (uridine-lactose synthesis, pseudouridine-protein synthesis). In an experiment with 7 male castrated pigmy goats subjected to a four-day fasting period the decrease of plasma allantoin, which was already apparent after 12 hours of fasting, was closely correlated with the increase of plasma free fatty acids. PMID- 1888273 TI - [Growth studies of bulls of the black pied dairy cattle breed during low feed levels. 3. Anabolism and energy metabolism at empty body weight at slaughter]. AB - In two long-term individual feeding experiments with rations very rich in roughage, nutrient and energy retention in the course of live weight development of black-and-white dairy bulls were determined. For this purpose, a total of 123 animals were slaughtered at the age of 5, 9, 12, 15, 18, 21 and 24 months, and the total body was analysed of 97 animals. The ascertained protein, fat and energy retention per day showed a clear dependence of the implemented level of nutrition. The results received compare well with the findings of earlier studies (PIEPER et al., 1984a). At a nutrition level (maintenance = 1.0) of 1.38 = 473 g gain of empty body [table: see text] at a nutrition level of 1.48 [context: see table] live weight range between 150 and 450 kg. The dynamics of the nutrient and energy retention in the course of live weight development is depicted in tables. PMID- 1888274 TI - First results on the incorporation and excretion of 15N from orally administered urea in lactating pony mares. AB - Two lactating pony mares were given oral offers of 20 g 15N urea [95 atom-% 15N excess (15N')] on 6 subsequent days. About 80% of the consumed 15N' were excreted via urine and faeces, but only about 2% via milk. The 15N' secreted via milk lysine only amounted to 0.04% of the 15N' intake. The recovery was about 90% in each case. Tissues with active metabolism had an unexpectedly high labelling (greater than 0.3 atom-% 15N'). The low extent of the conversion of oral urea N into milk-lysine speaks against an essential participation of the enteral synthesis in meeting the amino acid requirement of lactating mares. It was already concluded from this results that the determination of the amino acid requirement will be necessary for this group of performance. PMID- 1888275 TI - [Occupational medicine in European countries and in Yugoslavia]. AB - A recent publication on occupational health services in European countries prepared by the World Health Organization is reviewed. On the basis of guidance by the international organizations, the overall objectives of occupational health services are embodied in principles which are implemented in various ways in the practical activities undertaken in each country. The functions of occupational health services, organizational models, coverage, personnel, support systems (industrial hygiene, ergonomics, psychology, clinical occupational medicine) as well as research, training and funding are discussed. Comparison is made with the actual situation and development of occupational health service in Croatia with special reference to the conclusions drawn at a round table discussion organized by the Association of Occupational Health of the Croatian Medical Society in Pazin, in April 1991. PMID- 1888276 TI - [Characteristics of main and additional sleep time in workers on rotating shifts]. AB - Various sleep characteristics were examined among rotating shift workers (n = 603) and control workers (n = 113). The results showed the shift workers to have poorer sleep quality than the control group. In addition their main sleep episode was shorter on morning shift and longer on days off in comparison to controls. Shift workers' main sleep length and frequency of napping were affected by the situation in which they were taken (morning, afternoon, night shift or days off). In the group of shift workers the short main sleep episode on morning and night shifts was compensated by longer sleep on afternoon shift and days off. The short night shift sleep was additionally compensated by napping. However, naps taken on the morning shift did not prove to be compensatory. The length of the main sleep episode was affected by the situation in which sleep was taken also in the control group of workers. In this group only the longer main sleep episode on days off appeared to have a compensatory function for the short main sleep on working days. The relationship between sleep quality and main sleep duration was determined by the situation in which sleep was taken, while the relationship between sleep quality and napping was established only for the control group of workers. PMID- 1888277 TI - [Urinary cotinine as a marker for passive tobacco smoking]. AB - To provide an objective measure of the hazard smoking parents represent to their children's health, continue concentration in urine was measured by the colorimetric method using barbituric acid (DBA). A total of 205 children, aged 10 12, were examined. The results of laboratory tests were correlated with the data collected by interview. A significant difference in the average value of cotinine concentration was demonstrated between the children whose parents did not smoke (3.2 mumol/L) and those whose one parent smoked (5.8 mumol/L). An even larger concentration was recorded when both parents smoked (7.8 mumol/L). The largest cotinine concentration was determined in the urine of children--passive smokers whose both parents smoked and who did not have a room of their own (9.2 mumol/L). The difference in cotinine concentration between girls and boys was not statistically significant. PMID- 1888278 TI - [Immunologic and respiratory findings in workers on a pig farm]. AB - The prevalence of respiratory symptoms and ventilatory capacity in relation to immunological status were studied in 32 swine workers and in 39 controls. A large number of swine workers reacted to antigen of swine hair (34%) and to swine confinement antigen (28%) but also to other antigens such as animal food (78%), and corn flour (37%). Control workers showed comparable prevalence in their reaction to these antigens (17%, 25%, 51%, 25%). Increased IgE serum level was determined in three swine workers (9.4%) and in one control worker (2.6%). Swine workers with positive skin tests demonstrated significantly larger acute reductions in FEF50 and FEF25 than those with negative skin tests (P less than 0.01). The ventilatory capacity data measured before shift in swine workers with positive skin tests were significantly lower than the predicted normal values. Swine confinement antigen caused a dose-related contraction of guinea pig smooth muscle in vitro. Our data indicate that non-immunological reactions may be partly responsible for the acute and/or chronic changes in respiratory function. PMID- 1888279 TI - [Causes of permanent disability in professional drivers]. AB - In the period from 1984 to 1989 a total of 8139 professional drivers were examined in the Centre for Prevention, Diagnosis and Assessment of Work Ability in Rijeka. Of this number 347 were assessed as permanently disabled. On the basis of the Regulations on Health Requirements, with which motor vehicle drivers must comply, 130 of these 347 drivers were completely disabled for all driving categories (A, B, C, D and E categories). More than half the disabled professional drivers were aged from 18 to 47 years. The most frequent cause of disability of professional drivers was disease of the eyes and defective sight (34.3% of disabled). The second cause was alcoholism (19%) and the third cause was disease and conditions of the skeletal system and locomotor apparatus (11.5% of the total number of disabled drivers). PMID- 1888280 TI - [Protective effect of zinc in chromium poisoning in rats]. AB - The effect of a toxic trivalent chromium dose on histopathological changes in rat organs was investigated. To evaluate a protective effect of zinc, rats were treated with ZnCl2 two hours before chromium administration. The protective zinc action was best observed in respect to morphological changes in the organs of chromium poisoned rats, particularly in the liver. The lack of areas of focal necrosis on the liver capsule in the protected group of rats was the most evident macroscopic findings. The histopathological changes observed were in accordance with the results of own previous investigation of the changes in lactate dehydrogenase activity in rat organs induced by chromium and zinc. The mechanisms of the zinc protective effect against chromium poisoning are discussed. PMID- 1888281 TI - [Acute poisoning in children in Vojvodina]. AB - The paper deals with acute poisoning among children in Voivodina from the point of view of frequency, characteristics and regional differences. The histories of the poisoned children aged 0-16 years, who were hospitalized in all eleven in patient clinics in Voivodina during 1985, 1986, 1988 and 1989, were analysed. Acute poisoning in children accounted for 2.4% of hospital morbidity. The most frequent causes of poisoning were medicaments (60.6%), pesticides (8.7%), ethanol (6.34%), organic solvents (5.7%) and all other substances (18.35%). Poisoning occurred more often among boys than among girls (53.47%). The average age of the poisoned was 4.7 years. The average age of the poisoned girls was significantly higher than that of the poisoned boys. Poisoning usually took place during a "game", but a major number of poisonings was suicidal. There were great regional differences as regards the course of poisoning, sex and average age of the poisoned, circumstances of poisoning and period in which it happened. The children's age and circumstances of poisoning point to the absence of preventive measures or their failure. PMID- 1888282 TI - [Urinary incontinence in female workers in the area of Zagreb]. AB - To determine the incidence of urinary incontinence among female workers 383 women with different jobs from three firms were examined over a three-year period. Examination comprised a systematic gynaecological check-up and a questionnaire. The established incidence was 4.7%. Among the factors known to predispose damage to the pelvic muscles the number of births, physical work and body weight failed to show the expected impact, whereas age was highly significant in respect to the symptoms of incontinence (P less than 0.001). The age-related degeneration and involution of the genital tract can be cured if treatment is started early enough. Regression of symptoms was noticed in 66% of the treated women. PMID- 1888283 TI - [How should pharmacodynamic tests for respiratory tract obstruction be evaluated?]. AB - The factors that could influence the results of pharmacodynamic testing with beta 2 agonists in lung function diagnostics are discussed. These are: hypersecretion of the mucus, acute respiratory infection, tachyphylaxis of the adrenoceptors, therapy in the past 48 hours, patient's cooperation, and ambient or environmental pollution. The correct application, by inhalation, of selective sympathomimetics is described and differences between the basic values of lung function parameters and those following the salbutamol test are discussed. PMID- 1888284 TI - [Arterial hypertension and insulin resistance: physiopathogenic and therapeutic implications]. PMID- 1888285 TI - [Comparison of negative chronotropic action of nitrendipine, nifedipine and verapamil on the isolated right atrium of normotensive and renovascular hypertensive rats]. AB - PURPOSE: To study the negative chronotropic effects of nitrendipine, nifedipine and verapamil in isolated right atria from normotensive and renovascular hypertensive rats. MATERIAL AND METHODS: Hypertension (medium arterial pressure, MAP = 154 +/- 4 mmHg) was induced by applying a silver clip to the left renal artery and right nephrectomy. Control rats (MAP = 109 +/- 2 mmHg) were submitted to right nephrectomy only. The animals were studied 2 weeks after surgery. Different preparations were used to obtain cumulative dose-response curves (0.01 microM to 100 microM) with each drug. RESULTS: No difference in "in vitro" initial sinusal rate of control (243 +/- 7 bpm) and hypertensive (245 +/- 5 bpm) rats was observed. The negative chronotropic response produced by calcium channel blockers was similar in normotensive and hypertensive groups. 2 microM verapamil, 4 microM nitrendipine or 20 microM nifedipine was necessary to produce a 50% decrease of the initial sinusal rate. CONCLUSION: Sensitivity of the sinusal pacemaker to calcium antagonists does not change in this model of hypertension. Moreover, the negative chronotropic effect of nitrendipine is stronger than nifedipine and weaker than verapamil. PMID- 1888286 TI - [Infective endocarditis. Study of 83 cases at the Hospital da Santa Casa de Sao Paulo]. AB - PURPOSE: To analyse clinical aspects, diagnosis and treatment of infective endocarditis (IE), in order to guide medical procedures and indicate the surgical treatment. PATIENTS AND METHODS: 83 patients were submitted to clinical treatment of IE between January 1980 and December 1987; clinical aspects, laboratory and pathologic-anatomy findings, the site of infection and the entrance of micro organism were studied. RESULTS: 37 (44.6%) patients were males. Fever was present in 75 (90.4%) cases, cardiac murmur in 76 (91.5%), splenomegaly in 28 (33.7%) and heart failure (III and IV) in 32 (39.8%) patients. Blood culture was positive in 55.5%; staphylococcus 50% of blood cultures; anemia was present in 66 cases (79.5%) and high serum mucoprotein in 58 (92%); echocardiography was 85.7% positive. The mortality was 39.76%; congestive heart failure was the main cause of death; 78.1% of these ones occurred in the first 15 days of antibiotic therapy. The mitral valve was the one most impaired and the most frequent entrance of micro-organisms in oropharynx. CONCLUSION: Congestive heart failure, sepsis and systemic embolisms were the main complications that led the patient to death in course of IE, usually before 15 days of antibiotic-therapy. In these cases, we may hypothesize that prompt surgical treatment could have diminished the mortality of IE. PMID- 1888287 TI - [Evaluation of the PR intervals in normal and prolonged maximum limit with short QRS]. AB - PURPOSE: Evaluation of the A-V node function by determining the Wenckebach period (WP) and atropine response in cases of normal PR interval, PR interval at maximum normal range and prolonged PR interval, all with short QRS. PATIENTS AND METHODS: 129 patients, 79 male and 50 female, aged 17 to 84 years (mean 59), asymptomatic or with complaints of palpitations, dizziness, presyncope or syncope has been studied. ECG showed supra-ventricular tachycardia, first degree A-V block or intermittent Mobitz I type A-V block and sick sinus syndrome. Preexcitation (WPW) syndrome and longitudinal A-V dissociation were excluded. Electrical transoesophageal atrial stimulation was performed in all patients for evaluating the PR interval and WP. Atropine test was performed in a group of 16 patients. Based on the values of the WP, patients were divided into three groups: group I, WP greater than or equal to 125 ppm (N = 88); group II, WP ranging 125-110 ppm (N = 16) and group III, WP less than or equal to 110 ppm (N = 25). RESULTS: There was a good decreasing lineal correlation between the PR interval and the WP only in the group III (r = 0.76, p less than 0.01). PR interval greater than 240 ms had greatest and significant incidence in the group III in relation to the other groups in which the number of WP post-atropine normalization was observed. CONCLUSION: There is a strong linear decreasing correlation between the PR interval of the ECG and the WP in individuals with WP less than or equal to 110 ppm. PR interval greatest than 0.24 ms corresponds better to WP below 110 ppm (mean 90 ppm) and the majority of these patients do not normalize the WP with the atropine. We suggest the term "first degree A-V block" for those cases with PR interval greater than 240 ms and "A-V depression" for the cases with PR interval shorter than 240 ms when recorded on the surface electrocardiogram and have been normalized with atropine. PMID- 1888288 TI - [Clinical aspects and development of dilated cardiomyopathy in infants and children]. AB - PURPOSE: The evaluation of the clinical aspects of the dilated cardiomyopathy (DCM) in infants and children regarding, mainly, to the evolution and prognostic of this disease. PATIENTS AND METHODS: 38 patients divided in two groups: A) 22 infants till 22 (11.60 +/- 6.50) months of age, 15 female, and B) 15 children of 2 to 12 years of age (5.23 +/- 3.13) the majority males (10). A retrospective study was carried out based on the data from the patients's records. It was performed, in all the cases, a clinical, electrocardiographic, echocardiographic (M module and two dimensional echocardiography) and radiologic evaluation. RESULTS: The dyspnea on exercise (included sucking) was the predominant symptom in 15 (65.22%) patients of the A group and 10 (66.67%) of the B group followed by perilabial cyanosis in 7 (30.43%) and 6 (40%) patients, respectively. In the A group the clinical diagnostic hypothesis was inspecific myocarditis (IM) in 12 (52.17%), endocardial fibroelastosis (EFE), in 8 (34.79%), and "idiopathic" dilated cardiomyopathy (IDCM) in 3 (13.04%). In the B group to the diagnostic conclusion of myocarditis was made in 10 patients (66.67%)--5 of them IM--EFE in 3 (20%); and IDCM in 2 (13.33%). The average time of evolution was 5.48 months in the A group and 18.56 in the B group. In the A group the evolution was excellent in 3 (3.04%), good in 10 (43.46%), stable in 2 (8.70%) and bad in 1 (4.35%). In the B group, excellent in 8 (53.33%), good in 2 (20%) stable in 1 (6.67%). No bad evolution in this group. There was a decrease in the A group (4.34%); 6 patients in this group (26.09%) and 3 (20%) of the B group interrupt the follow-up. CONCLUSION: 1) The prognosis of infants with DCM including those with the diagnostic hypothesis of EFE seems to be less adverse than it could be supposed to be; 2) the prognostic in children with the diagnosis of DCM established above 2 years of age seems to be good; 3) the differential clinical diagnosis between EFE and IM is difficult and with no accuracy; 4) it is possible that the IM could be more prevalent in infants till 6 months of age than we suppose it was. PMID- 1888289 TI - [Modified Cooley technique for surgical repair of left ventricular aneurysms]. AB - PURPOSE: To evaluate early postoperative results of modified Cooley's technique of ventricular endoaneurysmorrhaphy. PATIENTS AND METHODS: Eight patients, seven males, with ages ranging 38.0 to 67.0 years (m = 51.2 +/- 11.4 years) and with postinfarction left ventricular aneurysms were submitted to surgical repair by a modified Cooley's technique of ventricular endoaneurysmorrhaphy. RESULTS: No postoperative complication occurred and all patients were discharged from the hospital asymptomatic on a mean time of 9.0 +/- 2.3 days after surgery. The mean cardiac index increased from 2.1 +/- 0.5 to 3.3 +/- 1.1 l/min (p less than 0.05) with a mean percentual increase of 53.0%. No patient required mechanical circulatory assistance after surgery and the pharmacological support could be interrupted soon. CONCLUSION: Ventricular endoaneurysmorrhaphy searchs to restore shape, contour and volume to the left ventricle and has shown excellent initial results. PMID- 1888290 TI - [Early exercise test after acute myocardial infarction]. AB - PURPOSE: To study the predischarge exercise testing importance in determining prognosis after acute myocardial infarction (AMI). PATIENTS AND METHODS: Treadmill exercise testing was performed in 50 stable and without complications patients with AMI, just before hospital discharge; there were 43 men and 7 women, mean age of 53.6 +/- 9.3 years. It was used the modified Naughton protocol and there were no casualties during the exercise testing. Patients were followed up for a mean period of 22.2 +/- 7.7 months. RESULTS: The test was positive in 32% of the patients, abnormal (inadequate blood pressure, heart rate response or arrhythmia) in 36% and normal in 42%. During the first year of follow-up, eleven patients presented with a serious cardiac event. There was one cardiovascular death, 6 patients with unstable angina, 2 reinfarctions and 7 patients had a coronary bypass revascularization. The cumulative risk for these events at one year after myocardial infarction was 50% in patients with a positive exercise test, and 5% in those with a normal exercise test (p less than 0.005). CONCLUSION: The predischarge exercise testing proved to be a simple and safe method to determine prognosis after acute myocardial infarction, identifying a high risk group early after the acute event. PMID- 1888291 TI - [Mitral valve aneurysm associated with mitral insufficiency in absence of aortic insufficiency]. AB - Two 31 year old patients were interned with cardiac insufficiency (functional class III). Case number one infective endocarditis with mitral valve 8 months before. Case number two had previous rheumatic disease. Both had severe mitral insufficiency and were submitted to replacement of mitral valve. Surgical findings included the presence of aneurysm mitral leaflet (posterior in case one and both in case two). The pathologic study showed mitral valve prolapse and signs of previous endocarditis in case one and rheumatic lesion in the other case. PMID- 1888292 TI - [Case 2/91 (Instituto do Coracao do Hospital das Clinicas--FMUSP)]. PMID- 1888293 TI - [Hypertensive urgencies and emergencies]. PMID- 1888294 TI - [The diagnosis of myocardial ischemia]. PMID- 1888295 TI - [Diagnosis of myocardial ischemia]. PMID- 1888296 TI - Prothrombin in myocardial infarct. PMID- 1888297 TI - [Streptokinase in myocardial infarction]. PMID- 1888298 TI - [Pulmonary artery pressure evaluation in adults by Doppler echocardiography]. AB - PURPOSE: To assess the role of pulsed Doppler echocardiography (PDE) in the indirect assessment of pulmonary artery (PA) pressure (P), analysing the pulmonary velocity blood flow curves (PVBFC) profile. PATIENTS AND METHODS: Sixty one adults with several kinds of heart disease were submitted to heart catheterization to obtain PAP (systolic, diastolic, mean), and other hemodynamic variables. A PDE examination was performed in all to obtain the PVBFC at the level of the pulmonic annulus. Qualitative features of the curve were analysed (morphological pattern, presence of pulmonic regurgitation) as well as quantitative data (acceleration time = AT, right ventricle ejection time = RVET index, AT/RVET index AT corrected for heart rate = ATC), which were compared to the invasive measurements. RESULTS: An abnormal rapid acceleration of the PVBFC, with triangular configuration, was noted in patient with pulmonary hypertension (PH), in contrast to the dome-like shape of the PVBFC in normal PAP. Pulmonary regurgitation was more frequent (p less than 0.05) in patients with severe PH (mean PAP greater than or equal to 40 mmHg), comparing with patients with PAP less than 40 mmHg. Inverse linear correlations were observed between AT and mean PAP, particularly when sinus rhythm was present (r = 0.89; p less than 0.05) excluding patients with atrial fibrilation (19 cases). CONCLUSION: PDE is an useful and noninvasive method for indirect evaluation of PAP in adults, especially during stable sinus rhythm, in heart rate range from 60 to 115 bpm. PMID- 1888299 TI - [Fatal active rheumatic disease. Study of 13 necropsy cases]. AB - PURPOSE: To study the clinical features of a group of patients with fatal acute rheumatic fever (ARF). PATIENTS AND METHODS: Thirteen patients with ARF, the ages ranged between 4.5 and 25 (mean 14) years. Eight patients were male. Patients were studied in two groups: group A of those 14 year-old or younger (8 cases), and group B of those older than 15 years (5 cases). RESULTS: Clinical presentation was fever and severe heart failure in all patients. In group A, it was the first attack of ARF in 5 patients. The time elapsed between beginning of symptoms and hospital admission ranged between 10 and 90 (mean 40) days. Mitral insufficiency occurred in all patients. The blood leukocyte count was greater than 10000 per mm3 in six cases. Atrioventricular block occurred in one case. Valvular vegetations were detected on echocardiogram in 4 cases. Two patients received antibiotic therapy. Surgical treatment of the valvular heart disease was carried on in one patient. In group B, it was the first ARF attack in 2 cases, the time elapsed between beginning of the symptoms and hospital admission ranged between 4 and 60 (mean 21) days. Leukocyte count greater than 10000 por mm3 occurred in 4 cases. Atrioventricular block was diagnosed in one case. Valvular vegetations on echocardiogram were detected in 2 patients. In two cases, the treatment was antibiotic therapy. Three patients were operated on. CONCLUSION: ARF may still be fatal, even in the first attack or in patients in the third decade of life. Other diagnoses are frequently considered, due to the intense clinical and laboratorial manifestations. PMID- 1888300 TI - [Use of implantable pacemaker in the treatment of paroxysmal supraventricular tachycardia refractory to pharmacologic therapy]. AB - PURPOSE: To evaluate the results with the use of an automatic antitachycardia pacemaker in patients with refractory paroxysmal supraventricular tachycardia. PATIENTS AND METHODS: Nine patients aged 32 to 63 years with symptoms from 2 to more than 40 years and prophylactic treatment with several antiarrhythmic drugs that had failed to control tachycardia. The frequency of attacks in the year before the implant was from 1 per month to 3 daily and 4 of patients required direct counter current cardioversion at least once. The electrophysiologic studies demonstrated atrioventricular (AV) nodal reentry in 6 and AV reentry utilizing an accessory AV connection in 4 patients (in one patient both mechanisms were present). The patients have been followed from 2 to 18 months. RESULTS: All patients experienced new episodes of the arrhythmia that were successfully terminated by the pacemaker. Two patients presented episodes of tachycardia not terminated by the pacemaker. These events were successfully treated by reprogramming the unit. The drug treatment was discontinued in 7 patients. CONCLUSION: The antitachycardia pacemaker proved to be an effective therapeutic tool in reentrant supraventricular tachycardia refractory to pharmacologic therapy. PMID- 1888301 TI - [Systemic-pulmonary shunts in congenital heart diseases with decreased pulmonary blood flow: critical analysis of the surgical techniques and immediate results]. AB - PURPOSE: To evaluate immediate postoperative results in children with congenital heart disease and decreased pulmonary blood flow who underwent a systemic to pulmonary shunt. PATIENTS AND METHODS: Sixty-four patients underwent surgery, 46.8% (30) of them males with ages from 1 day to 17 years old. They were divided in three groups: I--13 pts (20.3%) who underwent classical Blalock-Taussig (BT) shunt; II--46 pts (71.8%) who underwent modified BT shunts, 34 of them with polytetrafluoroetylene (PTFE) and 12 of them with umbilical vein shunts; III--5 pts (7.8%) with central anastomosis that were made with three different types of graft; 3 PTFE, umbilical vein and bovine mammary artery in one each. The simultaneous procedures were: section and suture of PDA--2, closure of systemic pulmonary collaterals--3, pulmonary valvotomy--3, right ventricular outflow patch -3, pulmonary branch stenosis (enlargement)--2. RESULTS: In group I there were 4 (30.7%) closures, with two immediate reoperation and a total mortality of 30.7%. In group II there were 4 closures (8.6%) and two reoperations with a mortality of 15.2% (7 cases). In group III there was one graft closure and an overall mortality of 80% (4 pts). When analysing deaths due to the shunt itself the mortality rate was respectively 15.3%, 8.6% and 40.0%. CONCLUSION: Modified BT operation was performed most frequently in our service; it was associated with less closure and mortality than the other types of shunt. It is considered our first alternative for a systemic-pulmonary shunt. PMID- 1888302 TI - [Myocardial revascularization after reperfusion in the acute phase of myocardial infarction]. AB - PURPOSE: To evaluate the coronary artery bypass grafting (CABG) after successful coronary reperfusion (CR) by streptokinase and/or percutaneous transluminal coronary angioplasty in acute myocardial infarction (AMI). PATIENTS AND METHODS: During 65-months period, 245 patients underwent CR during AMI. In 47 (19.2%) CABG were performed in the acute period due to multi-vessel disease (31%), residual lesion (20%) and post-reperfusion angina (17%). There were two distinct periods: in the first, between Jun/81 and Jun/83, 34 patients underwent CABG, 47 hours average after reperfusion; in the second, between Jul/83 and Nov/86, 13 patients underwent CABG, 7 days average after reperfusion. RESULTS: There were 7 deaths (21%) in the first period and 1 (8%) in the second one. CONCLUSION: After a multifactorial analysis the authors concluded that better results with inferior mortality (p less than 0.05) were obtained when CABG was performed later (mean 7 days) than in the immediate post-reperfusion period (mean 47 hours). PMID- 1888303 TI - [Percutaneous pulmonary valvuloplasty at the cardiovascular center of the Universidad de Los Andes]. AB - PURPOSE: To compare balloon valvuloplasty and surgical valvulotomy in the management of pulmonary valvar stenosis. PATIENTS AND METHODS: Balloon pulmonary valvuloplasty was performed in 10 consecutive patients, 6 girls and 4 boys, age ranges 3 to 19 years (mean 11), between April 1987 to November 1988. RESULTS: Immediate hemodynamic and angiographic changes consisted in reduction of the peak transvalvular gradient from 93 +/- 42 mmHg to 39 +/- 26 (p less than 0.01), the right ventricular systolic pressure from 108 +/- 16 mmHg to 58 +/- 27 mmHg (p less than 0.01) and in increasing of the pulmonary valve diameter from 9.59 +/- 3.28 mm to 19.55 +/- 6.16 mm (p less than 0.01) and the systolic pulmonary artery pressure from 15.15 +/- 3.28 mmHg to 18.4 +/- 6 (NS). No relationship between right ventricular systolic pressure and transpulmonary valvular gradient could be found. We only observed one case of mild pulmonary insufficiency as a complication of the procedure. The intermediate follow up (7 to 14 months), in 4 of 10 patients showed maintenance of the initial finding. CONCLUSION: The results of the percutaneous pulmonary valve valvuloplasty are as good as those obtained by the surgical valvulotomy. PMID- 1888304 TI - [Coronary angioplasty of moderate lesions (50 to 60%)]. AB - PURPOSE: To assess the efficacy of transluminal coronary angioplasty in patients with moderate (50-60%) coronary lesions. PATIENTS AND METHODS: One hundred and thirty nine patients, 108 (78%) male, mean age was 55 years, who underwent coronary angioplasty from August 1983 to January 1989. Clinical findings included stable angina in 91 (65%) and unstable angina in 48 (35%). Single vessel disease was the case for 117 (84%), whereas 22 (16%) had two vessel coronary artery disease. RESULTS: Primary success rate was 130 (94%). All patients with two vessel disease had complete revascularization. In the failure group there were 2 acute myocardial infarction (1.4%), and 4 (2.8%) emergency coronary artery by pass surgery. There were no in-hospital deaths. Of the 130 patients with success, 119 (92%) had late follow-up (mean time 31 months). At the end of the follow-up period we found 85 (71%) asymptomatic, while 27 (23%) had recurrence of symptoms. There were 2 late cardiovascular deaths. Fifty four patients underwent late angiography and 42 (78%) had maintenance of the result while 12 (22%) had restenosis, with a mean degree more severe than pre-coronary angioplasty. CONCLUSION: Coronary angioplasty of moderate lesions has a high success rate (94%); nevertheless the rate of major complications and restenosis is very similar to that of coronary angioplasty for severe stenosis. Such findings led us to reserve the indication of coronary angioplasty for moderate lesions for patients at higher risk with clear evidence of myocardial ischemia. PMID- 1888305 TI - [Intrapericardial lipoma]. AB - A 27 year-old female patient presented with atypical chest pain. 2-D echocardiogram and thorax computed tomography revealed intrapericardial tumor. The patient was operated on for removal of the tumor, which turned out to be two isolated lipomas. The patient had a rapid postoperative recuperation. PMID- 1888307 TI - [Neoplastic pulmonary embolism, subacute cor pulmonale]. PMID- 1888306 TI - [Assisted circulation with centrifugal pump for cardiogenic shock after extracorporeal surgery]. AB - A 59 year old woman with aneurysm of the left ventricle anterior wall developed heart failure, class III-IV (NYHA). The radioisotopic angiography showed left ventricular function impairment, ejection fraction of 16% and the aneurysm. She was submitted to aneurysm correction with bovine pericardium patch. In spite of technically successful cardiac surgery, the patient cannot be weaned from cardiopulmonary bypass with maximal pharmacological therapy and intra-ortic balloon pump. Then, we used Biomedicus centrifugal pump for left ventricular assistance. Cannulation was made by aorta and left atrial appendage. Myocardial function evolution was accompanied by hemodynamic parameters and by intra esophagic echocardiography. The patient was assisted during 42 hours. After this time, assist cannulas were removed in operating room without difficulty. She was submitted to another radioisotopic study on the 50th post-operative day and ejection fraction was 24%. She was discharged from hospital at 52th post operative day. Nowadays she is in NYHA class II at third post-operative month. More frequent utilization of circulatory assistance devices will reduce global mortality from cardiac surgery and improve safety in surgery of severe cardiac disease. PMID- 1888308 TI - [Effect of ticlopidine and dipyridamole on platelet aggregation and count in patients with chronic stable angina pectoris]. AB - PURPOSE: To compare the ticlopidine and dipyridamole effects on platelets count and aggregation in patients with stable coronary artery disease. PATIENTS AND METHODS: Eighty patients with stable coronary artery disease and mean of 58.3 +/- 5.8 years were studied. They were divided into two equal groups of 40 patients and each one treated with ticlopidine or dipyridamole. Platelets count and aggregation were examined before treatment and at first and fourth weeks of treatment. RESULTS: At the end of fourth week of treatment, spontaneous, induced by ADP or by adrenalin platelet aggregation inhibition was observed, respectively, in 82.5%, 72.5% e 67.5% of the patients in ticlopidine group. The spontaneous, induced by ADP or by adrenalin, platelet aggregation inhibition in the patients of dipyridamole group was, respectively, 40%, 30% e 27.5% (p less than 0.001). The platelets count did not change in both groups. CONCLUSION: The ticlopidine effect is much more evident in platelet aggregation inhibition than dipyridamole, and maybe a choice in the prevention of cardiovascular events. PMID- 1888309 TI - The origins of bovine brucellosis in New South Wales and its eradication. PMID- 1888311 TI - A survey of farmers' attitudes to services provided by consulting veterinarians to the Western Australian sheep industry. AB - A postal survey was conducted of 80 sheep farmers in the Kojonup and Esperance districts of Western Australia to establish what they wanted from a veterinary service. Twenty five of the farmers surveyed used a sheep consultant, 25 did not, and 30 were interested in employing one. Farmers were asked questions about themselves and their attitudes to private veterinarians who provide specialist services to sheep farmers. Data reported here showed that farmers wanted a veterinarian who lived in the district, was well trained in sheep management and production, was enthusiastic and had good communication skills. The service provided should be whole-farm and available to members of the consultant's group only. Regular newsletters and field days were necessary, but the provision of contract services, such as mulesing, lamb-marking, drenching, pregnancy testing and sheep classing, and 'fire-brigade' services for sick animals, were not rated as important. Most farmers were unwilling or unable to give a dollar value for the likely benefits of a consultancy service. Non-financial benefits included keeping farmers up to date with new technical developments and information. The survey also showed that a veterinarian specialising in services to sheep farmers could be confident of employment. PMID- 1888310 TI - A clinical trial of a topical preparation of miconazole, polymyxin and prednisolone in the treatment of otitis externa in dogs. AB - A topical preparation containing miconazole, polymyxin and prednisolone was shown to be more effective in the treatment of otitis externa in 167 dogs than 2 other ear preparations containing antibiotics, an antimycotic and a corticosteroid. With miconazole, polymyxin and prednisolone, the recurrence rate was 26.7% compared with 72.6% and 54.3% when the other products were used. The mean duration of treatment required to achieve resolution of clinical signs was 9.6 days, compared with 12.2 days and 13.0 days and no cases failed to respond to treatment, compared with 17.7% and 14.3%. Malassezia canis alone (71%) or in association with bacteria (18%) was recovered from 44 of 49 ears cultured. PMID- 1888312 TI - Pasteurella multocida septicaemia in fallow deer (Dama dama). AB - Thirteen of 100 fallow deer, aged between 6 months and 10 years, died over a 5 week period. The deaths occurred in 2 outbreaks 3 weeks apart. Both outbreaks were preceded by at least 3 days of cold wet and windy weather, and were associated with water-logged pastures. Affected animals were usually found dead, with a frothy blood-stained nasal discharge. In the 8 deer necropsied, gross lesions included widespread subserosal petechial haemorrhages, severe pulmonary congestion and oedema with froth-filled airways, and fibrinous pneumonia and pleurisy in 4 deer. Two deer, also, had extensive subcutaneous petechial and ecchymotic haemorrhages and oedema of skeletal musculature. Histologically, the most significant lesions were present in the lungs. Moderate to severe pulmonary congestion and oedema, with fibrinous exudation into alveoli and septal oedema, were present in all deer. In some deer these changes were accompanied by a diffuse infiltration with polymorphonuclear leucocytes. Pasteurella multocida was isolated from a range of tissues from 7 of 8 deer examined. The remaining animal had been treated with antibiotics 8 hours before death. The isolates had identical polyacrylamide gel electrophoresis patterns and were of the same antigenic type-Carter group A, Heddleston type 3,4. PMID- 1888313 TI - Clinical and pathological findings of Babesia infection in dogs. AB - The clinical and pathological findings of Babesia infection in 32 dogs in northern Australia are presented. Eleven different breed types were represented from 6 localities in north Queensland and one locality in northern Western Australia. Twenty three (72%) were males. Babesia-infected dogs were grouped by the degree of haematological disturbance and clinical severity: Acute babesiosis (25/32), all pups with severe haemolytic anaemia; subclinical carriers (5/32) with non-specific malaise, characterised haematologically by a normal erythrogram but marked leucopenia; chronic anaemia, observed in 2 adult dogs. Pups were azotaemic (serum urea greater than 6.6 mmol/l) and had elevated serum bilirubin levels (20.8 to 48.5 mmol/l). Total serum protein was usually within the normal range. Pups that died were also hypoglycaemic and severely hyperkalaemic (K+ greater than 10 mmol/l). Low parasitaemias in routine blood smears complicated diagnosis but smears made from ear or toe capillaries, or after haematocrit concentration, greatly enhanced finding parasitised cells. At necropsy, pallor and jaundice were the most consistent observations. Haemoglobinuric nephrosis, an active reticulo-endothelial system and capillaries packed with large numbers of infected erythrocytes were the main histopathological findings. A combination of imidocarb dipropionate at 5 mg/kg body weight, given intramuscularly, with fluid therapy and blood transfusion was the most successful treatment. PMID- 1888314 TI - Streptococcus dysgalactiae infection in calves. PMID- 1888315 TI - An unusual outbreak of contagious ovine ecthyma. PMID- 1888316 TI - Multifocal symmetrical encephalomyelopathy of Simmental cattle. PMID- 1888317 TI - Suspected poisoning of camels by Trema tomentosa (poison peach). PMID- 1888318 TI - Ixodes holocyclus in the Melbourne metropolitan area. PMID- 1888319 TI - Dog attacks on postal delivery officers in Queensland. PMID- 1888320 TI - Use of oxytocin to induce oviposition in a dystocic saltwater crocodile- Crocodylus porosus. PMID- 1888321 TI - Efficiency of inspection procedures for the detection of tuberculous lesions in cattle. PMID- 1888322 TI - Covariation bias and electrodermal responding in spider phobics before and after behavioural treatment. AB - The present study investigated whether a covariation bias is present in severe spider phobics and whether such bias is modified by successful treatment. In addition, this study sought to examine whether a covariation bias is linked to differential autonomic responding. Subjects were 20 untreated phobics, 19 treated phobics, and 18 no-fear controls. Subjects were exposed to a series of 72 slides comprising three categories: spiders (fear-relevant), mushrooms, and flowers. At slide offset one of three possible outcomes occurred: a shock, a tone, or nothing at all. All slide-outcome combinations occurred equally frequent. The results show that an equally strong covariation bias is present in severe spider phobics, in successfully treated phobics, and in no-fear controls. Thus, the present data only partially sustain earlier findings of Tomarken, A. J., Mineka, S. & Cook, M. (1989) (Journal of Abnormal Psychology, 98, 381-394). The covariation bias appeared to be mimicked by differentially heightened autonomic responding. The current data suggest that both the covariation bias and the heightened physiological responding reflect a "beloningness" between spider slides and aversive outcome. PMID- 1888323 TI - Visual palatability of food in patients with eating disorders and dieting women. AB - The effects of 19 meals of different caloric content on slides on palatability and hypothetical duration of consumption were investigated in 7 patients with anorexia nervosa, 17 patients with bulimia nervosa at the beginning and after 8 weeks of hospital treatment. Nine healthy females served as controls. At the beginning of treatment, palatability of low caloric food was significantly higher and hypothetical duration of consumption of high caloric food was significantly longer in patients when compared to controls. After 8 weeks, in the patients palatability of low caloric food had decreased. Dislike for high caloric food remained stable in anorexics. PMID- 1888324 TI - Changes in degree of sclerosis as a function of prophylactic treatment in cancer prone and CHD-prone probands. AB - One-hundred and ninety-two probands were selected on the basis of personality questionnaires as being cancer-prone (100) or CHD-prone (92). They were then randomly divided into a control and a treatment group, the latter receiving a special kind of behaviour therapy attempting to change the personality patterns in the direction of a healthier, more autonomous personality. Follow-up after 10 and 13 years disclosed significantly lower death rates in probands receiving prophylactic treatment than in controls. Of special interest was the degree of sclerosis in the fundus of the eye, rateds on a 3-point scale. This was significantly higher prior to therapy in the CHD-prone group than in the cancer prone group. Treatment reduced the degree of sclerosis, particularly in the CHD group; lack of treatment was followed by an increase in sclerosis. Similar but less marked changes were found in the cancer-prone group. Clearly psychological treatment affects significantly bodily functions associated with CHD. Other risk factors considered were systolic and diastolic blood pressure, blood cholesterol and blood sugar, all of which, together with personality, influenced the degree of sclerosis observed. PMID- 1888325 TI - Social phobia: individual response patterns and the long-term effects of behavioral and cognitive interventions. A follow-up study. AB - In this study the long-term effectiveness of Social Skills Training (SST) and Rational Emotive Therapy (RET), on social phobia was studied, as well as the differential influence of patient characteristics on treatment effectiveness. Fifty-seven patients were assessed 14 months after the post-test. Results showed that long-term effectiveness was independent of the response-pattern of the patients. Comparisons between methods, irrespective of the response-pattern of the patients, showed no differences in effectiveness in favor of either SST or RET. Explorative analysis indicated the potential predictive power for treatment outcome of confederate ratings of overt behavior on the SSIT. Patients who needed additional treatment appeared to perform significantly worse on this measure at the pretest. No factors could be traced that predict relapse after a relatively successful treatment. PMID- 1888326 TI - Anticipatory anxiety and avoidance in panic disorder with agoraphobia. AB - The present study utilized the responses of 34 patients with panic disorder with agoraphobia to investigate the occurrence and anticipation of panic attacks in relation to the avoidance of specific situations from the Fear Questionnaire [Marks & Mathews (1979) Behaviour Research and Therapy, 17, 263-267]. Results indicated that self-reports of avoidance of specific situations were often significantly correlated with the anticipation of panic but rarely with the occurrence of panic. The occurrence and anticipation of panic were also frequently associated with social phobic situations in addition to agoraphobic situations. PMID- 1888327 TI - Anxiety sensitivity and nonclinical panic attacks. AB - The present study examined anxiety sensitivity in relation to trait anxiety and the occurrence of nonclinical panic attacks in 265 subjects. Fifty percent of high anxiety sensitivity subjects reported panic attacks (both cued and spontaneous) in the past year. In addition, almost 42% of subjects with high anxiety sensitivity but no history of panic reported a high level of trait anxiety concerning physical danger. The results suggest that anxiety sensitivity is frequently not independent of other forms of anxiety. PMID- 1888329 TI - Alterations in protein synthesis in rat liver cells by in vitro and in vivo exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin. AB - Alterations in protein synthesis in rat liver cells were examined following in vitro and in vivo exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Primary cultured rat liver parenchymal cells were exposed to 1 nM TCDD for 23 and 47 hr. Synthesis of two proteins with molecular weights (Mr) of 26,000 and 39,000 (designated 26k-P and 39k-P, respectively), other than cytochrome P450, was increased markedly in the cells. These proteins did not have the same antigens as cytochromes P450IA1 and P450IA2. Synthesis of three proteins with Mrs of 24,000, 25,000 and 29,000, respectively, was decreased by TCDD. TCDD was administered to rats at a dose of 100 micrograms/kg body weight. The amount of five proteins (two proteins with Mr of 26,000, one of 36,000 and two of 39,000) was increased in TCDD-treated rat liver. However, the proteins increased in vivo by TCDD were distinguishable from 26k-P and 39k-P by two dimensional gel electrophoresis. PMID- 1888328 TI - Inhibition of cytosolic epoxide hydrolase by trans-3-phenylglycidols. AB - The inhibition of murine cytosolic epoxide hydrolase has been studied with both racemic and enantiomerically pure trans-3-phenylglycidols. These compounds are the first enantioselective, slow binding inhibitors of cytosolic epoxide hydrolase. The (2S,3S)-3-phenylglycidol enantiomer was always a better inhibitor than the (2R,3R)-enantiomer. When the I50 values of (2S,3S)- and (2R,3R)-3-(4 nitrophenyl)glycidol were compared, the (2S,3S)-enantiomer was at least a 750 fold better inhibitor (I50 = 1.6 microM) than the (2R,3R)-enantiomer (I50 = 1200 microM), and it was the most potent inhibitor tested in the 3-phenylglycidol series. If the hydroxyl group of the glycidol was masked or converted to another functionality, the potency of the inhibitor decreased and the (2S,3S)-enantiomer was not necessarily the better inhibitor. In addition, trans-3-phenylglycidols demonstrated slow binding inhibition of cytosolic epoxide hydrolase. Inhibitors without a hydroxyl group, or with a blocked hydroxyl group, were not slow binding inhibitors. These results suggested that the hydroxyl group was important in both enantioselectivity and time dependence of inhibition of cytosolic epoxide hydrolase by trans-3-phenylglycidols. The hydration pattern of (2S,3S)- and (2R,3R)-2,3-epoxy-3-(4- nitrophenyl)glycidol by cytosolic epoxide hydrolase also differed. When incorporation of [18O] from water catalyzed by cytosolic epoxide hydrolase was measured, the (2S,3S)-enantiomer gave 12% incorporation into the benzylic carbon and the (2R,3R)-enantiometer gave 40% incorporation into the benzylic carbon. Finally, trans-3-phenylglycidols were found to be poor inhibitors of microsomal epoxide hydrolase. PMID- 1888330 TI - Halysin, an antiplatelet Arg-Gly-Asp-containing snake venom peptide, as fibrinogen receptor antagonist. AB - By means of Sephadex G-75 and CM-Sephadex C-50 column chromatography and reverse phase HPLC, a low molecular weight (Mr = 7500), cysteine-rich peptide, halysin, was purified from Agkistrodon halys (mamushi) snake venom. Halysin is a potent platelet aggregation inhibitor that concentration-dependently inhibited human platelet aggregation stimulated by ADP, thrombin and collagen (IC50 = 0.16 to 0.36 microM) without affecting platelet secretion. It was active in inhibiting platelet aggregation of platelet-rich plasma and whole blood. Halysin had no effect on thromboxane B2 formation of platelets or intracellular Ca2+ mobilization of Quin 2-AM loaded platelets stimulated by thrombin. It inhibited the fibrinogen-induced aggregation of elastase-treated platelets. Halysin concentration-dependently inhibited the 125I-fibrinogen binding to ADP-stimulated platelets in a competitive manner (IC50 = 0.16 microM). 125I-Halysin bound to resting platelets (Kd = 1.6 x 10(-7) M) and to ADP-stimulated platelets (Kd = 3.4 x 10(-8) M) in a saturable manner. EDTA, the Arg-Gly-Asp (RGD)-containing snake venom peptides trigamin and rhodostomin, Arg-Gly-Asp-Ser (RGDS), and Gly-Gln-Gln His-His-Leu-Gly-Gly-Ala-Lys-Gln-Ala-Gly-Asp-Val blocked both 125I-fibrinogen binding and 125I-halysin binding to ADP-stimulated platelets. The monoclonal antibody, 7E3, raised against glycoprotein IIb-IIIa complex blocked both 125I fibrinogen and 125I-halysin binding, whereas 10E5 had no significant effect on halysin binding to ADP-stimulated platelets, indicating that 7E3 and halysin bind to an epitope which is different from that of 10E5. RGDS concentration dependently inhibited 125I-halysin binding in a competitive manner. We determined the primary structure of halysin which is a single peptide chain of 71 amino acid residues. An RGD sequence appeared in the carboxy-terminal domain of halysin. Halysin showed about an 85% identical sequence with trigamin which is a specific antagonist of fibrinogen receptor associated with glycoprotein IIb-IIIa complex. In conclusion, halysin inhibited platelet aggregation by interfering with fibrinogen binding to the fibrinogen receptor of the activated platelets. The RGD sequence of halysin plays an important role in the expression of its biological activity. PMID- 1888332 TI - Mitochondrial activity and cytotoxicity of vitamin A (retinol) in yeast and human cell cultures. Protective effect of antioxidants. AB - Vitamin A inhibited the growth of yeast and human cells in a dose-dependent but selective manner in cultures utilizing a non-fermentable carbon and energy source. At sub-inhibitory concentrations in yeast cultures (approximately 100 micrograms/mL), the vitamin had a stimulatory effect on the mitochondrial system, foreshortening the lag phase in the adaptation to non-fermentable substrate. At inhibitory concentrations, vitamin A depressed mitochondrial protein synthesis relative to cytoplasmic protein synthesis and induced the mitochondrial mutation petite but had little or no mutagenicity with respect to nuclear genes at the concentrations used. The vitamin showed a dose-dependent cytotoxicity (lethality) in both yeast and human cells. All of these deleterious effects were overcome to a large extent by the presence of antioxidants implicating free-radical metabolites in much of the toxicity. PMID- 1888331 TI - Comparative studies on coumarin and testosterone metabolism in mouse and human livers. Differential inhibitions by the anti-P450Coh antibody and metyrapone. AB - We have studied coumarin 7-hydroxylase (COH) and testosterone 15 alpha hydroxylase (15 alpha OH) activities in human liver microsomes and compared them with corresponding activities catalysed by members of the P450IIA sub-family in DBA/2N mouse liver microsomes. Human liver contained low levels of 15 alpha OH (about 5-30 pmol/min/mg protein) when compared with control mouse liver microsomes (about 200 pmol/min/mg protein). The anti-P450Coh antibody efficiently inhibited mouse liver 15 alpha OH, also 7 alpha OH (which is a member of the P450IIA sub-family), but it did not inhibit human 15 alpha OH or other testosterone hydroxylases. In mouse liver microsomes, metyrapone preferentially inhibited 15 alpha OH, but in human liver microsomes it inhibited all testosterone hydroxylations measured, including 15 alpha OH (IC50 = 2.0-5.0 microM). Metyrapone clearly inhibited COH in mouse liver microsomes, but interestingly it had no effect on COH activity in human liver microsomes, although these two isozymes have earlier been shown to be immunologically similar. On the basis of available evidence human and mouse P450Coh isozymes seem to be orthologous enzymes whereas the present results indicate that the human 15 alpha OH is different from the mouse P45015 alpha. PMID- 1888333 TI - Cytochrome P450 maintenance and diazepam metabolism in cultured rat hepatocytes. AB - Diazepam metabolism has been investigated in rat hepatocytes cultured for 3, 24, 48 and 72 hr under five different conditions. Although four of the treatments studied reduced markedly the spontaneous loss of cytochrome P450, they had different effects on the metabolism of diazepam (DZ) presumably by affecting the relative proportions of cytochrome P450 isozymes during the period of culture. Thus P450 medium or dimethyl sulphoxide-supplemented medium maintained the rate of disappearance of DZ from the culture medium and metabolite profile in 24 hr cultures at the initial levels found in 3 hr cultures, while culture at 30 degrees or in metyrapone-containing medium resulted in the production of oxazepam, a metabolite normally only produced by dog, monkey and human hepatocytes. These findings indicate that the well recognized phenotypic alteration of cytochrome P450-dependent mono-oxygenase activities that occurs when rat hepatocytes are cultured in different media can result in a range of metabolic options that are normally only available in other animal species. PMID- 1888334 TI - Induction of glutathione-S-transferase and heat-shock proteins in rat liver after ethylene oxide exposure. AB - Defense mechanisms in rat liver against depletion of glutathione (GSH) and cellular injuries induced by ethylene oxide (EO) were studied. Rats were exposed to EO under either high dose (1300 ppm for 4 hr, once) or low dose (500 ppm for 6 hr, three times a week for 6 weeks) conditions. The hepatic content of GSH decreased dramatically after EO treatment, probably due to detoxication of EO. After the high dose treatment the hepatic GSH content fell by 90% of the control values but recovered within 10 to 15 hr. EO reacts directly with a variety of cellular macromolecules but all rats survived the exposure. Since the metabolites of EO are ethylene glycol and GSH-conjugates, the enzymatic activities of epoxide hydrolase and glutathione-S-transferase (GST) were determined. Only GST activity was found to occur after low dose chronic exposure. The defense mechanism at mRNA level was investigated using probes for GST and several heat-shock proteins (hsps). Enhanced accumulation of GST mRNA was detectable during the recovery period of rats after both high and low dose exposure to EO. Interestingly, both hsp32 (less than 40-fold) and hsp90 (less than 3-fold) mRNA increased after high dose exposure but the mRNA level of one of the major heat-shock proteins, hsp70, did not change under these conditions. Diethylmaleate, which is known to be a GSH depleter in liver, induced hsp32 mRNA only in rat liver, while hsp70 and hsp90 mRNA levels did not change when GSH was depleted. These results suggest that individual heat-shock proteins are induced in different ways under unphysiological conditions such as EO exposure. PMID- 1888335 TI - Effect of diallyl sulfide, a naturally occurring anti-carcinogen, on glutathione dependent detoxification enzymes of female CD-1 mouse tissues. AB - The present studies were undertaken to elucidate the mechanism(s) of the anti neoplastic effect of diallyl sulfide (allyl sulfide, DAS), a naturally occurring organosulfide abundant in vegetables of the Allium genus, against benzo[a]pyrene (B[a]P)-induced carcinogenesis in the mouse. DAS treatment caused a significant increase in glutathione S-transferase (GST) activity, an enzyme system responsible for detoxification of a variety of electrophilic xenobiotics including several harmful B[a]P metabolites, of mouse stomach in a dose-dependent manner. This activity in the stomach of mice treated with 25, 50 and 75 mumol DAS was higher by 1.13-, 1.20- and 1.58-fold, respectively, when compared to the control. Purification and quantitation of GST from equal amounts (1.2 g) of control and 50 mumol DAS-treated mice stomach tissues demonstrated that elevation in activity occurred as a result of increased de novo synthesis of the enzyme protein. DAS treatment also resulted in increased pulmonary GST activity, but not in a dose-dependent fashion. On the other hand, treatment of mice with DAS did not alter hepatic GST activity. Interestingly, a small but statistically significant (P less than or equal to 0.05) reduction in kidney GST activity was observed in mice treated with 50 or 75 mumol DAS, as compared to the control. The effect of DAS treatment was also assessed on glutathione (GSH) peroxidase activity, another GSH-dependent detoxification enzyme, in mouse tissues. Treatment of animals with 25, 50 and 75 mumol DAS increased stomach GSH peroxidase activity by 1.64-, 1.93- and 2.52-fold, respectively, over the control. This enzyme activity in the lungs of mice treated with 25, 50 and 75 mumol DAS was higher by 1.44-, 1.54- and 1.21-fold, respectively, when compared to the control. On the other hand, GSH peroxidase activity in liver and kidney was unchanged by DAS treatment. These results suggest that DAS and perhaps other naturally occurring organosulfur compounds may exert an anti-neoplastic effect by modulating GSH-dependent detoxification enzymes. PMID- 1888336 TI - Identification of mouse liver aldehyde dehydrogenases that catalyze the oxidation of retinaldehyde to retinoic acid. AB - NAD(P)-linked aldehyde dehydrogenases catalyze the oxidation of a wide variety of aldehydes. Thirteen of these enzymes have been identified in mouse tissues; eleven are found in the liver. Some are substrate-nonspecific; others are relatively substrate-specific. The present investigation sought to determine which of these enzymes are operative in catalyzing the oxidation of retinaldehyde to retinoic acid, a metabolite of vitamin A that promotes the differentiation of epithelial and other cells. Spectrophotometric and HPLC assays were used for this purpose. Enzyme-catalyzed oxidation of retinaldehyde (25 microM) was restricted to the cytosol (105,000 g supernatant fraction) and occurred at a rate of 211 nmol/min/g liver; oxidation of acetaldehyde (4 mM) by this fraction proceeds about ten times faster. At least 90% of this activity was NAD dependent. Of the approximately 10% that was apparently NAD independent, two-thirds was inhibited by 1 mM pyridoxal, a known inhibitor of aldehyde oxidase. Of the six cytosolic aldehyde dehydrogenases, only two, viz. AHD-2 and AHD-7, catalyzed the oxidation of retinaldehyde to retinoic acid. An additional NAD-dependent enzyme, viz. xanthine oxidase (dehydrogenase form), also catalyzed the reaction. Catalysis by AHD-2 accounted for more than 90% of the total NAD-dependent activity. Km values were 0.7, 0.6 and 0.9 microM, respectively, for the AHD-2-, AHD-7- and xanthine oxidase (dehydrogenase form)-catalyzed reaction. AHD-4, an aldehyde dehydrogenase found in the cytosol of mouse stomach epithelium and cornea, did not catalyze the reaction. PMID- 1888337 TI - Differential effects of oltipraz and its oxy-analogue on the viability of Schistosoma mansoni and the activity of glutathione S-transferase. AB - Adult worms of Schistosoma mansoni recovered from mice treated with oltipraz (OPZ) showed a significant diminution in their ability to reduce 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) to formazan, a measure of parasite viability. Incubation of glutathione S-transferase (GST) from S. mansoni with OPZ resulted in a time- and concentration-dependent inhibition of enzyme activity. RP 36,642 (an inactive oxy-derivative of OPZ) had a minimal effect on the viability of the worms and no effect on GST activity. The structural integrity of OPZ, particularly the thione sulphur, appears to be necessary for expression of the antischistosomal effects of the drug. OPZ-induced inhibition of GST was non-competitive with either reduced glutathione (GSH) or 1 chloro-2,4-dinitrobenzene (CDNB), indicating that the drug is not a substrate for GST-catalysed conjugation reactions. In addition, the inhibition of GST could not be reversed by dialysis or repurification of the enzyme via a GSH-agarose affinity column. The effects of OPZ on GST activity could render the parasite vulnerable to damage by host-derived reactive oxygen species and aldehydic products of lipid peroxidation. The effects of OPZ on GST activity may play a role in the antischistosomal action of OPZ. PMID- 1888339 TI - [Structure of tryptic fragments of a neurotoxin from black widow spider venom]. AB - The N-terminal amino acid sequence of a neurotoxin from the venom of Latrodectus mactans tredecimguttatus (alpha-latrotoxin) was determined. Latrotoxin was subjected to the tryptic cleavage and total or partial amino acid sequences of 25 peptides were established. In total the tryptic fragments contained 252 amino acid residues. Essential structural information on cloning of the latrotoxin structural gene was obtained. PMID- 1888338 TI - Variability of sarin-induced hypothermia in mice: investigation into incidence and mechanism. PMID- 1888340 TI - [Photosystem II of rye. Nucleotide sequence of psbD, psbI genes encoding reaction center proteins]. AB - Structures of the rye chloroplast DNA regions, containing psbD and psbI genes coding for the components of the reaction centre of photosystem II, D2 protein and I polypeptide, respectively, have been determined. The gene trnS for tRNA(Ser) (GCU) is located 111 bp downstream from the stop codon of the psbI gene on the opposite strand. The high homology between the rye BamHI-fragment comprising these genes and his counterpart from wheat are discussed. PMID- 1888341 TI - [Detection of two types of internal core structures of gram-negative bacteria lipopolysaccharides using chromophore markers]. PMID- 1888342 TI - [Biopolymer fragments containing residues of glycosylphosphtates. 6. Synthesis of phosphodiethers of alpha-D-galactopyranose--fragments of yeast phosphogalactanes from Sporobolomyces and capsule antigen of Escherichia coli K52]. AB - Syntheses of methyl 6-(alpha-D-galactopyranosyl phosphate)- and p-nitrophenyl 3 (alpha-D-galactopyranosyl phosphate)-alpha-D-galactopyranosides were performed through coupling of 2,3,4,6-tetra-O-benzoyl-alpha-D-galactopyranosyl hydrogenphosphonate with the partially acylated galactopyranosides, in the presence of trimethylacetyl chloride, followed by oxidation and debenzoylation. The data of 1H, 13C, and 31P NMR spectra of the synthesized phosphate diesters are reported. PMID- 1888343 TI - [Study of the structure of anthracycline antibiotics by ERIAD mass spectrometry]. AB - Fragmentation of antibiotics daunorubicin, carminomycin, doxorubicin and their semisynthetic analogues under conditions of the new mass spectrometry method ERIAD is discussed. Signals of protonated molecular ion (M + H)+ and ions of fragments are present in all the mass spectra. The results are compared with literary data obtained by means of other (EI and FAB MS) mass spectrometry methods. PMID- 1888344 TI - [Use of mass spectrometry with chemical ionization in screening antibacterial antibiotics with a broad spectrum of action (aminoglycosides and macrolides)]. AB - It is shown that mass-spectrometry with ammonia desorption chemical ionization (ADCI) can be used for identification of aminoglycosides and macrolides at the initial stages of screening. ADCI can also be used for selection of strains which form the lowest amounts of by-products, as well as for optimization of biosynthetic conditions. PMID- 1888345 TI - Efficacy of behavioral versus triazolam treatment in persistent sleep-onset insomnia. AB - OBJECTIVE: This study compared differential effects of behavioral therapy and triazolam in a clinical population with sleep-onset insomnia. Triazolam was hypothesized to decrease sleep latency and frequency and duration of awakening, with some effects during the first night's administration. But at follow-up, sleep measures were predicted to return to baseline levels. Behavioral treatment was hypothesized to effect sleep after 2 or more weeks of training which persisted at follow-up. METHOD: Thirty patients with average sleep latencies of 81.48 minutes, who reported chronic insomnia for an average of 2.6 years, were randomly assigned to one of two treatment groups: behavioral stimulus control/relaxation training and triazolam. RESULTS: Both treatments decreased sleep latency but differentially. Triazolam was effective immediately but maintained only some gains at follow-up. Behavioral treatment decreased sleep latency beginning the second week, when subjects expected no improvement, with gains maintained at follow-up. Comparisons showed that triazolam group latencies returned toward baseline, while behavioral group gains were maintained at follow up. CONCLUSIONS: Triazolam treatment showed superior immediate treatment effects, while behavioral treatment showed superior treatment effects at follow-up, effects that accrued during the training period and differentially persisted at follow-up. One treatment strategy implied by these results would be to combine these two interventions concurrently. This would seem to use the immediate effects produced by the medication until the behavioral skills were learned, at which point medication would be terminated. This strategy could offer immediate relief and sustained effects at drug termination. PMID- 1888346 TI - Access to information about AIDS. AB - Medical information related to human immunodeficiency virus (HIV) infection is highly diverse, and the practicing physician or researcher may find specific information difficult to locate. To provide timely access to medical information on topics related to the acquired immunodeficiency syndrome (AIDS), several computer-based products have recently been developed. Some are available from vendors of online information systems, whereas others are available only on CD ROM or floppy disk. We review several computer-based products. AIDSLINE is the most comprehensive bibliographic index, AIDSTRIALS contains specific information about ongoing unpublished investigational studies, and AIDS Knowledge Base from San Francisco General Hospital is an up-to-date electronic textbook covering all aspects of AIDS. COMPACT LIBRARY: AIDS operates on a microcomputer and combines several databases, including full-text AIDS-related articles from nine major medical journals. AIDS References from the Bureau of Hygiene and Tropical Diseases provides critical analysis of publications worldwide. Although smaller in size than AIDSLINE, about one third of the publications covered by this resource are not covered by AIDSLINE. PMID- 1888347 TI - Anaphylactoid reaction to intravenous hydrocortisone sodium succinate: a case report and literature review. AB - Reports of corticosteroid sensitivity reactions are rare in the medical literature. We report an anaphylactoid reaction to hydrocortisone sodium succinate given intravenously which occurred on two occasions during treatment of a patient for asthma. Intradermal testing with a wide range of steroid preparations gave positive results with hydrocortisone sodium succinate, methylprednisolone sodium succinate, methylprednisolone sodium succinate and methylprednisolone acetate. No reactions occurred to dexamethasone sodium phosphate administered intravenously, prednisolone given orally or beclomethasone dipropionate by inhalation. Results of a radioallergosorbent test (RAST) were negative for hydrocortisone sodium succinate. PMID- 1888348 TI - Analysing ordered categorical data. PMID- 1888349 TI - Choosing a partner in general practice. PMID- 1888350 TI - Sudden cardiac death: management of high-risk patients. AB - Sudden cardiac death remains a leading cause of death in the United States, accounting for more than 350,000 deaths each year, and the survival rate of victims remains low. Most survivors face a significant risk for recurrence. The typical substrate is chronic--abnormal myocardium with fibrosis (often from previous myocardial infarction) and left ventricular dysfunction. Acute triggers for sudden cardiac death are primarily electrical, ischemic, metabolic, neurohormonal, and pharmacologic. In most electrocardiographically documented cases of sudden cardiac death, the trigger-substrate interaction appears to result in ventricular tachycardia and fibrillation. After initial resuscitation, survivors need a thorough cardiovascular evaluation, including definition of coronary anatomy, left ventricular function, and wall-motion abnormalities, as well as an electrophysiologic evaluation. An attempt must be made to determine what each survivor's correctable triggers are. Management should address all reversible triggers, such as acute ischemia and electrolyte abnormalities, and should include modifying or correcting the arrhythmogenic substrate. Empiric antiarrhythmic therapy offers no advantage in such modification. Pharmacologic therapy with antiarrhythmic drugs should be guided by an objective therapeutic endpoint, which is best accomplished through the use of programmed ventricular stimulation and serial electrophysiologic studies. Other therapeutic options include surgical suppression of ventricular tachycardia and implantation of a cardioverter defibrillator. PMID- 1888351 TI - A piece of my mind. Fare well. PMID- 1888352 TI - Unintended pregnancy among teenagers: important roles for primary care providers. PMID- 1888353 TI - Coronary risk factors six to twelve months after coronary artery bypass surgery. 1986 compared with 1990. AB - A 1986 study found that coronary risk factors were receiving insufficient attention in patients who had recently undergone coronary artery bypass grafting. This issue was readdressed in a like group of 100 patients from the same surgical unit three and a half years later, in 1990, to ascertain whether risk factor management had improved over the period. An increased proportion of patients in 1990 were undergoing active management of hypertension and hyperlipidaemia. Only 25% of patients in 1990 manifested hypercholesterolaemia (cholesterol levels greater than or equal to 6.5 mmol/L) compared with 60% in 1986. Five per cent of patients in 1990 manifested diastolic hypertension (diastolic pressure greater than or equal to 95 mmHg) compared with 23% in 1986. Such patients appear better managed in 1990 than they were in 1986. PMID- 1888355 TI - The way forward. AB - At the end of November the Department of Health held a seminar in London on the topic of oral health education. An invited audience of 60 heard presentations about the problems in this field and how Department-funded experimental projects have sought to overcome them. These presentations were followed by a discussion about possible ways forward. PMID- 1888354 TI - Evaluation of the routine examination of nine month old infants. AB - During the month of March 1988, 880 (85.6%) of the 1027 babies born in New Zealand during the first week of June 1987 were examined by either a Plunket nurse or a paediatrician. Sixty-nine percent of the babies were European, 16.9% Maori, 6.8% from the Pacific Islands and 4.4% other nationalities. Previously unknown conditions or abnormalities that required further assessment or treatment were discovered in 8.3% of babies. Abnormalities were found in: 7.3% of European infants; 10.1% of the Maori infants; 18.3% of the Pacific Island infants and 2.6% of the others. Other topics considered of significance to the examiner but not directly associated with the nine month examination (eg, maternal health problem), were recorded in 24% of cases. There was no significant difference across the three main ethnic groups. Similar results were recorded irrespective of whether the examination was undertaken by a doctor or a nurse. We believe the nine month examination should be continued but the present policy of recommending that preferably general practitioners carry out the examination should be reassessed. PMID- 1888356 TI - ECT response and blood pressure reduction. PMID- 1888357 TI - Immunisation and homoeopathy. PMID- 1888358 TI - Physiotherapy for stress urinary incontinence: a national survey. AB - OBJECTIVE: To study the physiotherapeutic treatment of urinary stress incontinence in England. DESIGN: Postal questionnaire survey. SETTING: All 192 English district health authorities. SUBJECTS: One physiotherapist from each district who was primarily concerned with urinary incontinence. A consensus view was requested. MAIN OUTCOME MEASURES: Responses to questionnaire and analysis of a visual analogue scale to indicate effectiveness. RESULTS: There was a 98% response rate. Treatment was often by senior physiotherapists (108 senior I grade or above) who, in 117 districts, claimed to have made a specialty of treating the condition. Gynaecologists and obstetricians were far more likely to refer patients than any other agency (147 respondents said that they were the commonest source of referral). One hundred and fifty four respondents stated that physiotherapy was usually used as the first line of treatment. Pelvic floor exercises and interferential treatment were most commonly used (by 178 and 144 respondents respectively) and thought to be the most effective, especially in combination, though various techniques were used in applying them. Positive motivation (108), recent onset of symptoms (55), and youth (40) were viewed optimistically, and obesity (60), previous surgery (59), prolapse (42), and a chronic cough (36) were considered to be bad prognostic features. The number of patients treated varied greatly (range 10-360) between districts and was poorly correlated with catchment size (correlation coefficient 0.3). CONCLUSIONS: As physiotherapists are treating considerable numbers of patients with stress incontinence research is urgently needed to produce efficacy data to enable rationalisation of resources to cater for the whole population. PMID- 1888359 TI - Cancer of the breast: a study of 1520 consecutive patients operated on between 1960 and 1980. AB - A retrospective study was carried out of 1520 consecutive patients with breast cancer operated on at the Hopital Notre-Dame in Montreal between 1960 and 1980. Age and hormonal status of the patient, and duration, size, location, histologic type and stage of the tumour were studied. The authors grouped the patients according to four types of surgical treatment: radical (487 patients), modified radical (497 patients) and simple (220 patients) mastectomies and conservative procedures (316 patients). Adjuvant treatments included radiotherapy in 60%, hormone therapy in 4.7% and chemotherapy in 6.7% of patients. Overall survival at 5, 10 and 15 years was 71.3%, 58.7% and 51.1%; in patients with stage I disease, survival rates were, respectively, 86%, 78% and 72%; rates for patients with stage II disease were 74%, 62% and 53%. The population characteristics and survival rates were similar to those reported by others. The four types of treatment did not produce significantly different survival rates in patients with stage I lesions. However, this was not the case in patients with stage II and III lesions in whom simple mastectomy (McWhirter procedure) was associated with significantly worse results. Finally, this study confirmed the prognostic importance of stage, size of the tumour and degree of axillary lymph-node involvement. PMID- 1888360 TI - Helicobacter pylori gastritis mimicking gastric carcinoma at CT evaluation. AB - The abdominal computed tomographic (CT) scans from 61 patients with biopsy-proved Helicobacter (formerly Campylobacter) pylori gastritis were retrospectively reviewed. The CT scans were interpreted on the basis of the original report of the findings at CT examination and without knowledge of the results of biopsy. Of 19 patients (31%) with gastric abnormalities at CT, 14 (74%) had inflammatory changes initially reported as suspicious for gastric malignancy; malignancy was entertained as the primary diagnosis in four of those patients. In five of the 19 abnormal cases (26%), the diagnosis with CT was gastritis. The two major patterns of severe H pylori infection identified were (a) circumferential antral wall thickening and (b) thickening of the posterior gastric wall along the greater curvature, with or without evidence of ulceration. Thickening averaged 1.5-2.0 cm in cases suspicious for malignancy. The majority of abnormalities involved the gastric antrum (68%). No cases demonstrated significant adenopathy, obliteration of fat planes, or invasion of adjacent organs. PMID- 1888361 TI - Adequacy of general practitioners' premises for minor surgery. AB - OBJECTIVE: Assessment of facilities for minor surgery in general practitioners' premises. DESIGN: Independent inspection of premises and equipment. SETTING: Large urban district. SUBJECTS: Premises of all general practitioners who applied to be reimbursed for minor surgery. MAIN OUTCOME MEASURE: Fullfilment of 14 pre selected criteria. RESULTS: 69 of 111 premises met all criteria and were approved; 23 failed on only one criterion. The commonest reasons for failure were inadequate record keeping and lack of resuscitation equipment. Twelve practices had out of date adrenaline. CONCLUSIONS: Most premises are suitable for minor surgery, some with attention needed to record keeping. Practices must pay careful attention to the expiry date of adrenaline. PMID- 1888362 TI - Preventing the spread of HIV infection. PMID- 1888363 TI - Abortion forms. PMID- 1888364 TI - Adequacy of general practitioner's premises for minor surgery. PMID- 1888365 TI - Response to the editorial: Developing a national plan for schizophrenia research. PMID- 1888366 TI - Connectology problems with swan neck peritoneal dialysis catheters. PMID- 1888367 TI - Delayed traumatic cranial nerve. PMID- 1888368 TI - Breast cancer screening. PMID- 1888369 TI - Electrophysiologic studies for cardiac arrest. PMID- 1888370 TI - 'The way forward'. PMID- 1888371 TI - Dopamine and schizophrenia. PMID- 1888372 TI - Reichenstein disease. PMID- 1888373 TI - Oral BCAA in the treatment of chronic hepatic encephalopathy. PMID- 1888375 TI - Early surgery for essential infantile esotropia. PMID- 1888374 TI - Development of array applicators for superficial hyperthermia. PMID- 1888376 TI - Aluminum accumulation in patients with chronic renal disease. PMID- 1888378 TI - Nursing's minimum data set. PMID- 1888377 TI - Rural general practitioners. PMID- 1888379 TI - Thrombosis in injured small vessels. PMID- 1888380 TI - Eating disorders in patients with diabetes. PMID- 1888381 TI - Confidential reporting by physicians. PMID- 1888382 TI - Spontaneous resolution of congenital nephrotic syndrome in a neonate. PMID- 1888383 TI - Marker genotyping errors in old data on X-linkage in bipolar illness. AB - Investigations of linkage markers of the X-chromosome colorblindness region in bipolar manic-depressive illness (BP) have yielded inconsistent results, with linkage accepted in some and rejected in other studies. Although genetic heterogeneity has been proposed as the reason for differences, other possibilities exist, including systematic procedural errors. Statistical evidence for linkage between the markers, Xg and colorblindness, is present in a series of papers on bipolar illness reported in 1972-1975. The linkage implied by this reanalysis is spurious, since the two markers are at opposite ends of the X chromosome. The presumptive reason for this spurious linkage is that it is a result of systematic genotyping errors. The support provided by these data to the X-linkage hypothesis in BP illness is thus diminished. That is, the linkage to illness may depend on systematic errors in marker genotyping. In general, the possible causes of inconsistency between linkage reports may be divided into statistical and systematic causes. Statistical causes would generally consist of chance differences in sampling, such as might occur under genetic heterogeneity. If this occurs, the reports rejecting linkage may be false negatives, or the reports detecting linkage may be false-positive results. Systematic causes of differences among reports could include systematic errors (or variations) in procedures, including ascertainment, diagnosis, genotyping, or analysis. Consistency of the marker map in a particular study with the known marker map is one test for systematic errors in genotyping. PMID- 1888384 TI - Patient data in child psychiatry. PMID- 1888385 TI - Acute hydrops of gall bladder. PMID- 1888386 TI - Do universal precautions reduce needlestick injuries? PMID- 1888387 TI - Testing for immunity after hepatitis B vaccination. PMID- 1888388 TI - Ifosfamide administration recommendation questioned. PMID- 1888389 TI - Clinical skills of foreign medical graduates. PMID- 1888390 TI - [Helicobacter pylori gastritis: a new infectious disease. Reflections from a personal experience]. AB - To determine the relationship of microscopic chronic antral gastritis to Helicobacter pylori, 69 consecutive patients were studied. In a prospective longitudinal study, at least 2 successive gastroscopies with antral biopsies were performed (177 investigations on the whole). Sixty six of the 69 patients were treated with various therapeutic regimens i.e. antiulcer drugs and/or antibiotics. The type and intensity of inflammation (as based on whole inflammatory infiltrate density, polymorphonuclear cells presence or absence and IgA and IgM plasma cells counts) were correlated with H. pylori status (Giemsa staining and/or biopsy culture). The presence of the organism (Hp) and the gastritis were significantly correlated (high grade of whole inflammatory infiltrate Hp + ve: 98/109 90%, Hp-ve: 9/61 15%, p less than 0.001--presence of neutrophil PMNC Hp + ve: 80/109 73%, Hp-ve: 1/61 2%; p less than 0.001--IgA and IgM plasma cells respectively Hp + ve: 7.6 +/- 6.6, 10.6 +/- 7.1, Hp-ve 1.9 +/- 2.9, 4.2 +/- 4.5; p less than 0.005). Clearance and/or eradication of H. pylori after antibiotic treatment were associated with the disappearance of chronic gastritis activity and a statistically significant decrease of whole inflammatory infiltrate density (p less than 0.001) and IgA (p less than 0.005) and IgM (p less than 0.01) plasma cells counts. Mucosal inflammation was unchanged in case of H. pylori persistence and inflammation worsening occurred in case of infection relapse. H. pylori gastric mucosa colonization seemed to be responsible for the antral chronic inflammation associated with its presence.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1888391 TI - Sources and control of error in industrial hygiene measurements. AB - Many sources of error exist in industrial hygiene measurements. Errors may be systematic or random. Eliminating or controlling systematic and random error during measurement, analysis, and data interpretation is a matter of aggressive quality control/quality assurance and appropriate statistical treatment of data. The occupational health care professional should be aware of error sources in industrial hygiene measurements and be on the lookout for flawed exposure estimates. PMID- 1888392 TI - Heat stress disorders. Old problems, new implications. AB - Occupational health nurses must always be aware of changing job tasks that create new classes of employees at risk for developing heat stress disorders. Examples include chemical handlers or asbestos containment specialists who must wear non permeable protective clothing. Heat induced occupational illnesses and injuries, and reduced productivity occur in situations in which the total heat load (environment plus metabolic heat) exceeds the capacities of the body to maintain normal body functions without strain. Health screening should include evaluation of an employee's age, sex, body size, level of fitness, chronic diseases, use of medications, drugs and alcohol, and ability to acclimate. Prevention of heat stress disorders is a team effort. The occupational health nurse, plant engineer, safety/industrial hygienist, and the employee all impact on the success of any heat stress disorder prevention program. Without cooperation, the possibility for harm exists. PMID- 1888394 TI - Occupational health nurses' attitudes toward cancer. AB - Attitudes toward cancer held by a study population of 100 occupational health nurses were not significantly different than a normative reference group and did not indicate a negative attitude toward cancer. The majority of the literature reviewed supported a more negative attitude toward cancer than exhibited by either the normative group or the occupational health nurses in this study. Since this study was limited to one geographic location, a population of occupational health nurses in a different geographical area should be studied and the results compared to further establish reliability. PMID- 1888393 TI - Teaching employees breast self examination. Factors that may influence practice. AB - Breast self examination is a widely known technique used for detection of breast lumps. Many women do not practice monthly breast self examination, although it has been proven that with early detection the prognosis of breast cancer can be improved greatly. When tend to be taught, or learn about, breast self examination at an early age. The educational techniques used during the instruction can influence the practice of BSE later on. Health professionals can make a difference in the practice of BSE by communicating the value of this detection technique. BSE is a viable breast cancer detection technique that employees can be taught easily in employee wellness programs by health professionals. PMID- 1888395 TI - Advance directives. Educating employees about the living will and the durable power of attorney for health care. PMID- 1888396 TI - Farm accidents and injuries among farm families and workers. A pilot study. AB - Farm accident facts traditionally have been difficult to collect because of the wide array of farm family and non-family involvement in farming practices. Areas commonly involved in farm related accidents include farm machinery, tractor overturns, farm animals, farm trucks, hand and power tools, household items, chemicals, and garden equipment. Two purposes of this descriptive study were to examine, over a 1 year period, the demographic features and types, severity, and mechanisms of injury among farm families and their workers in a representative county in South Carolina, and to develop a two part mail-out questionnaire for data collection relative to farm work related accidents. The researcher concluded that farm accidents are sparsely researched; that traditional data collection methods are difficult, expensive, and time consuming; and that mail-out questionnaires are not a very effective method of collecting data relative to farm accidents, since farmers proved very reluctant to report accidents. PMID- 1888397 TI - Shiftwork: its effect on workers. AB - Shiftworkers have more complaints in three specific areas: sleep-wake disorders, gastrointestinal disorders, and cardiovascular disorders. After 1 to 4 months of effective shiftworking, more than 50% of shiftworkers leave shiftwork after suffering from fatigue, sleep disturbance, and other problems. In addition, older workers seem less able to adjust to shiftwork and are more likely to leave sooner. Three main factors influence the ability to predict adjustment to shiftwork: rigidity/flexibility of sleeping habits; ability/inability to overcome drowsiness; and morningness/eveningness. Occupational health nurses can influence shiftwork policy and workers' health through health promotion policies aimed at predicting which workers might be less tolerant of shiftwork, scheduling shiftwork so it follows the sun, and providing early diagnosis and rapid treatment to workers with symptoms that need management. PMID- 1888398 TI - The evolving American family. AB - The American family is undergoing constant changes that influence the work environment. The contrast between the U.S. parental support system and other industrialized nations is dramatic. Despite the fact that the United States has no mandated federal policy, a number of corporations are instituting their own policies because they believe family care and education are good business. Occupational health professionals are in a key position to take an active role in seeking to balance work and family issues. PMID- 1888399 TI - Family medical leave. An employee benefit for working caregivers of elderly family members. AB - Future trends include a decrease in the number of adult children, an increase in the number of individuals over age 65, single parent families, working women, and individuals with no health care insurance. As more women with multiple roles and responsibilities enter and continue as part of the work force, employers recognize the need for support of family issues. Currently many employers lack initiative to make these needed changes. The occupational health nurses' role in relation to future policy for working caregivers includes assessment of how employment and caregiving impact work performance, job satisfaction, and health; and participation in defining public policy issues. PMID- 1888400 TI - Smoking cessation programs in the workplace. Review and recommendations for occupational health nurses. AB - The worksite offers occupational health nurses unique opportunities to assist workers in their smoking cessation efforts. For nurses to be effective in this endeavor, they must be knowledgeable about the various quit smoking strategies that have met with some success. Based on the review of the research, there is no "magic bullet" to offer smokers who want to quit. Occupational health nurses have an opportunity, therefore, to use multiple approaches and design programs to fit the specific needs of the smokers in their practice. Published reports of nurses' involvement in workplace smoking cessation programs are sparse. It is crucial that occupational health nurses spearhead smoking cessation efforts at the workplace and communicate the results of these enterprises. PMID- 1888401 TI - Managing at a distance. PMID- 1888402 TI - Missed myocardial ischaemia in the accident & emergency department: E.C.G. a need for audit? AB - Accident & Emergency Department Senior House Officers rely heavily on their ECG interpretation skills in the diagnosis and management of patients with chest pain. This prospective double-blind study was designed to test the accuracy with which Accident & Emergency Senior House Officers interpret ECGs, by comparing their interpretation with that of a Consultant Cardiologist. ECGs from 279 of 314 consecutive patients with chest pain were analysed. Ninety per cent of normal electrocardiographs and 57% of abnormal ECGs were correctly interpreted. Despite the inaccurate interpretation of 43% of abnormal ECGs, 96.5% of the patients in the study were considered to have been managed correctly. Audit of all ECGs recorded in the Accident & Emergency Department should be undertaken by someone with experience of ECG interpretation. New A&E staff should receive training in the interpretation of ECGs. PMID- 1888403 TI - A review of medical airlifts by a search and rescue squadron on the east coast of England over 18 years. AB - This paper reviews the medical workload of a Royal Air Force Search and Rescue squadron on the East Coast of England over a period of 18 years and their association with the principal receiving hospitals in that area. It illustrates the effects of improvements in road networks on the workload of the squadron and contrasts the use of military helicopters with established U.K. civilian helicopter schemes. PMID- 1888404 TI - The value of routine expiratory chest films in the diagnosis of pneumothorax. PMID- 1888405 TI - The importance of elbow aspiration when treating radial head fractures. AB - A prospective study of elbow aspiration was performed to assess the effect of this procedure on pain relief and function following Type I and II fractures of the radial head. Aspiration of the haemarthrosis produced dramatic pain relief in 77% of elbows thus treated. Earlier return of function was also noted for these elbows compared to controls. We recommend elbow aspiration for patients with these fractures to both relieve pain and restore early function. PMID- 1888406 TI - A study of the eye care provided by an accident and emergency department. AB - The eye care provided by an Accident and Emergency (A&E) Department was prospectively studied over a 2-month period. Six out of a total of 506 patients were deemed to have been treated unsatisfactorily by the A&E Department. None of these patients suffered serious sequelae. Approximately one in three of those patients seen solely by A&E staff failed to have their visual acuity recorded. PMID- 1888407 TI - A study to compare the use of fusidic acid viscous eye drops and chloramphenicol eye ointment in an accident and emergency department. AB - A total of 300 patients attending an Accident and Emergency department with ophthalmic complaints needing topical antibiotic treatment were treated with fucithalmic or chloramphenicol (chloromycetin). Their compliance and the incidence of side effects were assessed. There was a 70.3% response rate to the questionnaire. Of the patients 51.3% using fucithalmic completed the 5 day course compared with 37.2% of those taking chloramphenicol. However, no patients were found to have suffered as a result of failing to complete the course. The incidence of side effects was similar in both groups. PMID- 1888408 TI - An evaluation of a logbook for trainees in accident and emergency medicine in the United Kingdom. AB - The ideal requirements of a logbook for trainees in accident and emergency medicine in the United Kingdom were sought by means of a postal survey of 100 Senior Registrars and recently-appointed Consultants in the specialty. Sixty-two replies were received. An overwhelming majority supported ACLS and ATLS certification, as well as formal training in Management/Clinical Budgeting skills, the use of Information Technology, dealing with medicolegal issues and Disaster Planning. Secondments to General Practice, Regional Poisons Centres and the Emergency Services were similarly recommended. A total of 71% (42 responders) approved of a minimum of 3 years experience in an A&E Department before appointment as a Senior Registrar in the specialty. The majority of responders disapproved of acquiring laboratory-based skills. The results of the survey are discussed and suggestions for the possible role of a logbook are made. PMID- 1888409 TI - Minor trauma--major problem. Neck injuries, retropharyngeal haematoma and emergency airway management. PMID- 1888410 TI - Extensive subcutaneous bleeding after cardiopulmonary resuscitation and thrombolytic therapy. AB - A patient with acute myocardial infarction, complicated by pre-hospital cardiac arrest, was treated with anistreplase, heparin and aspirin following resuscitation. She developed a large lower lip haematoma and extensive bruising over the chest wall ten hours after thrombolytic therapy. A blood transfusion was required. PMID- 1888411 TI - Delayed presentation of perforation of the ileum following seat belt trauma. AB - A 36-year-old man presented with an acute abdomen due to perforation of the terminal ileum, 26 days after sustaining blunt abdominal trauma from a seat belt. He had been completely well and undertaking vigorous physical exercise since the injury. This is the first reported case of this type of injury presenting after a long asymptomatic interval. PMID- 1888412 TI - Hand injury in a child--a rare adverse effect of rear seatbelt use. PMID- 1888413 TI - Pulse electromagnetic energy and pre-tibial lacerations: a randomized clinical trial. PMID- 1888414 TI - The 'ten-to-fifteen' syndrome. PMID- 1888415 TI - Cyanoacrylate tissue adhesive. PMID- 1888416 TI - A system of feedback from out-patient clinics. PMID- 1888417 TI - Felis silvestris. PMID- 1888418 TI - Swallowed foreign body. PMID- 1888419 TI - Violent crime and victim support. PMID- 1888420 TI - International repatriation following overseas disasters. AB - The repatriation of 33 hospitalized patients to the United Kingdom following the Joigny coach accident in 1990 is described. The repatriation was undertaken by medical staff from St Bartholomew's Hospital Careflight project and EuropAssistance using a chartered McDonnell Douglas 83 aircraft. All patients were repatriated without mishap, but a number of difficulties were encountered. It is recommended that agreement is reached in advance as to the organization that should handle overseas disasters involving British citizens. The organization should have expertise in repatriation as well as close ties with the NHS. A protocol should be designed and adhered to. The initial response should involve despatching a team to the disaster country and provision of a control centre in the U.K. Special arrangements need to be made for staff and equipment. Liason with the airlines and ambulance services is essential. PMID- 1888421 TI - Chest pain in the accident and emergency department: is chest radiography worthwhile? AB - Four per cent of patients attend the Accident and Emergency Department (A&E) present with chest pain. In this prospective study of 297 patients the value of chest radiography is assessed. Overall, 23% of chest X-rays (CXRs) had an abnormality which influenced management of the patient, rising to 40% in those patients admitted to Coronary Care. Twenty-nine per cent of CXRs were misinterpreted by Casualty Officers but resulted in the mismanagement of only six patients (3.3%). Potentially serious errors were averted by early CXR audit by a Radiologist. PMID- 1888422 TI - [Stress and the endocrine system. A contribution to the value of endocrine parameters in anesthesia and surgery]. AB - This study examined prospectively the effects of different anaesthetic techniques on the plasma concentrations of adrenocorticotrophic hormone (ACTH), aldosterone, cortisol, dehydroepiandrosterone (17-DHEA), insulin, prolactin, thyroxine, triiodothyronine as well as the effects on the plasma concentrations of epinephrine, norepinephrine and dopamine. Forty patients for trauma surgery were randomly allocated to one of the following anaesthetic techniques: halothane N2O/O2-anaesthesia, isoflurane-N2O/O2-anaesthesia, midazolam-fentanyl-N2O/O2 anaesthesia, midazolam-ketamine-N2O/O2-anaesthesia or tramadol-N2O/O2 anaesthesia. The results of this endocrinological study demonstrate differences in the quality of the anaesthetic techniques used even without extreme stress situations for the patient. The elimination of pain can reduce, but not avoid, endocrinologic response to stress. Endocrine values are influenced by a lot of different control mechanisms. It is not always possible to distinguish between pharmacologic and indirect or direct effects of anaesthesia or surgery. For this reason, single plasma hormone levels should not be overvalued and equated with "stress" indicators, which is a much more complicated issue. PMID- 1888423 TI - [The blood level of gamma-aminobutyric acid in patients with liver cirrhosis and portacaval anastomosis]. AB - Venous blood was collected from 21 patients with liver cirrhosis and portocaval anastomosis for routine laboratory tests and determination of GABA levels by radioreceptor assay. The patients additionally underwent psychometric tests for determining the degree of hepatic encephalopathy. No differences were seen in psychometric tests and laboratory parameters between patients and normals. However, GABA serum levels showed a 10-fold increase and the difference was highly significant. The fact that these patients did not show any signs of hepatic encephalopathy is probably due to an intact blood-brain barrier that prevents the uncontrolled influx of GABA. Therefore, not even high GABA serum levels are associated with symptoms of encephalopathy. PMID- 1888424 TI - [Spontaneous and evoked electroencephalograms in experimental incomplete cerebral ischemia]. AB - In the present study changes in spontaneous EEG and somatosensory evoked potentials (SEP) under incomplete cerebral ischaemia and in the following reperfusion phase were examined in 8 goats. The neurophysiological parameters were compared with global cerebral blood flow (CBF). At CBF values below 37 ml/100 g/min significant reduction in the EEG power density occurred with a shift of the dominant frequency to lower frequencies. The cortical SEP amplitudes increased significantly with simultaneous increases in latencies. In contrast subcortical components were not affected. In the reperfusion period no complete remission of EEG and SEP changes occurred despite occasional CBF values above the baseline values. The study demonstrates that neurophysiological monitoring can show early functional changes in cases of incomplete cerebral ischaemia. PMID- 1888425 TI - [The clinical assessment of tissue oxygenation. The significance of hemodynamic and oxygen transport-related parameters]. AB - Adequate matching of the tissue O2 supply to the cellular O2 demands depends on the integrity of all components of the O2 transport system. The quality of O2 uptake by the lungs as well as O2 transport to the tissues can be assessed nowadays in the clinical setting. However, even if O2 uptake by the lungs and O2 transport to the tissues are normal cellular O2 supply may nevertheless be inadequate, if gas and substrate exchange are impaired on the tissue level. This may occur when nutritive blood flow is disturbed, as in patients with sepsis and ARDS. The hemodynamic monitoring parameters that are available in the clinical setting (i.e. systemic blood pressure, heart rate, cardiac filling pressures and art. blood gases) are only poor reflectors of the adequacy of tissue oxygenation. This review attempts to evaluate the extent to which the commonly measured hemodynamic variables relate to O2 transport and tissue oxygenation. PMID- 1888426 TI - [Reasons for the persistent lethality of malignant hyperthermia and recommendations for its reduction]. AB - Dantrolene is the only known specific treatment of malignant hyperthermia (MH). Following official approval an intravenous formulation of dantrolene became clinically available for emergency treatment of MH. At that time it had been anticipated, that with dantrolene therapy combined with constant vigilance each case of MH could be treated successfully and the mortality rate should be close to zero. Surprisingly enough, reports of death due to MH continue to be published up to the present. Analysis of case reports revealed the following reasons for the discrepancy between the expectations and the clinical reality: 1. Delay in early diagnosis due to preoccupation with the name-giving symptom hyperthermia: lack of MH-sensitive monitoring (i.e. capnometry, pulse oximetry, blood gas analysis). 2. Preoccupation with non specific facets of therapy: measures such as cooling, change of the anaesthesia machine, transfer of the patient to the intensive care unit or the administration of drugs which have been shown to be ineffective in treating MH may not only be a waste of time, but fully disregard the prime factor in therapy--intravenous administration of dantrolene. 3. Administration of an insufficient amount of dantrolene and delayed start of specific therapy due to failure to have immediate access to intravenous dantrolene. 4. Failure to increase minute ventilation immediately after making the diagnosis to meet elevated metabolic demands. A recommendation is presented how to diagnose, to treat and prevent MH, considering present day diagnostic and therapeutic measures in the presence of the presumptive diagnosis of MH. PMID- 1888427 TI - [A computer-controlled closed circle system for ventilation during anesthesia and intensive care and its possibilities for patient monitoring]. AB - A computer feed back controlled anaesthesia- and intensive care ventilator has been developed with on-line and separate lung function measurement. The system design is built on the principle of a totally closed circuit (closed rebreathing respirometer) and an inspiratory "high flow", the gas being rotated through the closed circuit unidirectionally by a blower with 70 l/min. Ventilation is performed by metal membranes freely movable in membrane chambers with an internal part included into the closed circuit and an external part connected to pressurized air controlling inspiratory valves expiratory valves. The electronic valves are software controlled by the computer to exactly perform the desired preset ventilatory mode. Membrane movement are on-line measured capacitively and transformed into respective flow and volume values, whereby the compressibility of the system gas (on-line pressure recording) is taken into account. Volatile anaesthetic gases are feed back controlled to preset end expiratory values (MAC controlled anaesthesia), circuit volume is maintained by N20-addition and oxygen is added to maintain the desired present inspiratory concentration measured with paramagnetic oxygen sensors. Ergonometric aspects led to the triangular from of the new anaesthesia and intensive care ventilator with the controlling service screen turnable to all three sides of the ventilator (high flexibility of the user) and all necessary equipment and material included into the "Anaesthesia workstation". All measured and present parameters are continuously displayed on the service (computer) screen and entered into the computer-memory in minute cycles with a memory capacity of 75 h anaesthesia. At any desired moment the memorized values can be transferred to IBM-compatible disc systems for storage or into the respective data management systems, thus at the end of anaesthesia, at the end of the working day or at the end of the week. PMID- 1888428 TI - [Carbamazepine poisoning]. AB - Due to the increased indications of using carbamazepine, a higher number of intoxications is to be expected. A case report is given of a 42-year-old patient who took about 250 tablets (50 g) carbamazepine (Finlepsin) in a suicide attempt. The maximum serum level of carbamazepine was 118.74 mumol/l. After a gastric lavage and the use of activated charcoal the detoxication was carried out by forced diuresis and one-time haemodialysis. The unconscious patient was ventilated for 8 days after intubation. Two hours after admission three generalised seizures occurred. A long-term hypotension and electrolyte shifts were balanced and a bronchoscopy and lavage were necessary. Bronchopneumonia occurred as a complication. The patient became conscious on the 5th day of treatment, the extubation was accomplished on the 12th day and on the 15th day she was transferred to the psychiatric clinic for further treatment of the basic disease. Since a specific antidote does not exist, general intensive therapeutic measure after carbamazepine intoxication are discussed. After gastric lavage to eliminate the poison, the patient should receive hourly doses of activated charcoal plus vigorous cathartic-like solutions of mannitol and sorbitol and forced diuresis. In case of complicated coma haemoperfusion is recommended. PMID- 1888429 TI - Peripheral lymph node homing receptor (LECAM-1). PMID- 1888430 TI - Cytokines in T-cell development. AB - The thymus provides a unique environment for the development of T cells, supporting both precursor cell proliferation and differentiation. The control of these processes is unknown but they may be mediated by cytokines, or other soluble factors, or by interactions with specific elements of the thymic stroma. Here, Simon Carding, Adrian Hayday and Kim Bottomly describe cellular, immunochemical and molecular studies of the production and action of cytokines within the human and mouse thymus and demonstrate their essential role in T-cell development. PMID- 1888431 TI - Invariant involvement of IL-2 in thymocyte differentiation. PMID- 1888432 TI - The discovery of the immunological function of the thymus. PMID- 1888433 TI - Tumor-cell-targeted cytokine gene therapy. PMID- 1888434 TI - O6-methylguanine-DNA methyltransferase and human cancer chemotherapy. AB - Two kinds of human tumor cell strains having different activity of O6 methylguanine-DNA methyltransferase (O6-MT) were transplanted into nude mice. Then the mice were injected intraperitoneally with bifunctional alkylating agent 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU). The tumors with low O6-MT activity were quickly suppressed or cured. The result suggests that some tumors, if provisionally determined with low O6-MT activity, might be efficiently cured by treatment with ACNU. This probably opens a new way for human cancer chemotherapy. PMID- 1888435 TI - Potentiated effect of vagal stimulation and hormonal agents on pancreatic exocrine secretion in dogs. AB - Chronic experiments were made on eighteen dogs with Thomas pancreatic fistula and gastric fistula. Both in chronic and acute experiments the degenerated right cervical vagus nerve was stimulated by electrical shock and the endogenous secretin and CCK was released by means of duodenal acidification (D. A.). The exogenous secretin, atropine and lidocaine were infused to analyse the interrelationship of neurohormones in the pancreatic exocrine secretion. The results were as follows. In chronic experiments the pancreatic secretory latency was shorter and volume larger than that in acute experiments induced by D. A. The difference is very significant (P less than 0.001). Both vagotomy and atropine significantly inhibited pancreatic secretion induced by D. A. (P less than 0.01). Lidocaine infused into duodenum inhibited pancreatic secretion induced by D. A. as well. When vagal stimulation was combined with D. A., either simultaneously or successively, the pancreatic secretion was increased more than the additive sum obtained by separate action of vagal stimulation and D. A. or secretin. In view of the above-mentioned facts, the author suggests that vagal impulses combined with D. A. or secretin act on the pancreatic exocrine secretion, and that the interaction of nerve and hormones appear to be mutually potentiated. PMID- 1888436 TI - Effect of pre-flight treatment with constant magnetic field on development of Artemia eggs retrieved from Chinese Satellite "8885". AB - Dry winter eggs of Artemia salina were treated with a 30-60 mT inhomogeneous constant magnetic field for 113 h, and then carried by Chinese Satellite "8885" to its spaceflight for 8 days. Their early development rate and hatching ratio were observed on the 10th, 31st, 65th and 227th days after the accomplishment of the flight. Three main results were obtained as follows: (i) The treatment accelerated the development of the eggs not flown; (ii) it also enhanced the resistance of the flown eggs against unfavorable spaceflight effects (retarding early development and lowering the hatching ratio), and promoted the recovering ability of the flown eggs from the affected state; and (iii) the latent beneficial effect produced by treatment was found to be very durable, still appearing in the development of the treated eggs on the 318th day after treatment (the 227th day after the flight). PMID- 1888437 TI - Studies on steroidal plant-growth regulators (XVII)--a new synthesis of homobrassinolide and (22S, 23S)-22, 23-epi-homobrassinolide. AB - Homobrassinolide (2) and (22S, 23S)-22,23-epi-homobrassinolide (4) were synthesized from stigmasterol in seven steps respectively in 4.7% and 24.1% overall yields. The ratio of 2 to 4 is 1:5. The key step is the highly regioselective formation of the B-homo-7-oxa-lactone ring by oxidation of an enol silyl ether with 3-chloro-peroxybenzoic acid. PMID- 1888438 TI - An efficient site-directed mutagenesis using polymerase chain reaction. AB - We report here a simple and efficient method for site-directed mutagenesis using polymerase chain reaction (PCR). In constructing a new expression plasmid for the EcoRI restriction gene, we made two point mutations. While one created a new SalI site prior to the SD sequence, the other replaced Glu144 with Lys. A 1.5 kb SalI PstI fragment isolated from pER101 was used as the template. Two 25 mer oligonucleotide primers containing the desired mutations were synthesized and used to direct PCR amplification with Taq DNA polymerase. About 0.5 microgram of the 0.49 kb fragment was obtained from 0.05 microgram of the 1.5 kb fragment by carrying out polymerase chain reaction for 30 cycles. As calculated theoretically, 99% of the product contained the desired mutations. The product was cloned into pUC19 using SalI and PstI, two of the transformed colonies were randomly chosen for sequence analysis, and both of them were shown to contain the desired mutations. Finally, the amplified fragment was cloned into pER304 to place the EcoRI (Lys144) gene directly under the control of the lambda PL promoter. PMID- 1888439 TI - Effect of stress on drug hypersensitivity. PMID- 1888440 TI - Effect of drug treatment on quality of life in mild to moderate heart failure. AB - The most frequently reported symptoms in heart failure are fatigue and dyspnoea, which limit exercise tolerance. However, several surveys reveal other changes in physical and psychological well-being which affect the patient's perception of 'quality of life'. The introduction of new treatments for heart failure has stimulated interest in their impact on quality of life. Until recently, attempts to quantify well-being were restricted to assessment of symptoms which affect exercise capacity or classification of the functional capacity of the patient from his ability to perform everyday tasks. Although drug treatment can improve these measures, they are insensitive to change and also provide little information on the more subtle disturbances which patients may perceive as important determinants of their overall well-being. More comprehensive assessments of quality of life have been devised and validated in heart failure. Early results indicate that inotropic drugs such as digoxin and xamoterol can improve these measures. However, at present there is too little information from studies using these questionnaires to compare the wider benefits of individual drug treatments. PMID- 1888442 TI - Acute cyclosporin overdose. A review of present clinical experience. AB - Although cyclosporin is widely used in transplant patients, experience regarding the consequences of an overdose is limited. This article summarises the data available on 27 patients with oral (n = 20) or parenteral (n = 7) overdosage of cyclosporin. The available clinical data are consistent with predictions derived from animal toxicological studies, suggesting a low acute toxicity of the drug in humans. Acute oral overdoses result in minimal clinical manifestations and/or mild degrees of renal dysfunction, primarily in patients with previously impaired kidney function. Acute parenteral overdoses may have more serious consequences, premature neonates being at particular risk of developing life-threatening reactions. Determinations of blood concentrations of cyclosporin are of limited use in the management of patients with acute overdose. Guidelines are suggested for the management of such patients. PMID- 1888443 TI - Risks and benefits of the treatment of heart failure. Current status. AB - Congestive heart failure is an increasingly common patient problem. It is a multisystem disease that involves not only the heart but also the kidneys and neurohormonal systems. Any treatment for heart failure should address depressed contractility and exercise intolerance, as well as control compensatory mechanisms. There are many different approaches to the treatment of congestive heart failure: among the drugs used are diuretics, digitalis compounds, nitrates, calcium channel blockers, beta-blockers, beta-agonists, vasodilators, angiotensin converting enzyme (ACE) inhibitors and the new phosphodiesterase inhibitors. The therapy usually involves a multiple drug treatment plan to achieve the maximum effect for the patient with the lowest incidence of side effects. Heart failure involves a large spectrum of patients with left ventricular dysfunction, and success at achieving treatment goals with these patients will vary with the severity of that symptom. A major concern is that increasing contractility may further damage the myocardium and shorten the survival of these patients, although there is as yet no evidence of such shortening. The new phosphodiesterase inhibitor drugs are an exciting development in the treatment of heart failure, because they add a dimension to the treatment for patients who are not sufficiently improved by a regimen of digoxin, diuretics and ACE inhibitors. Any new heart failure medication should be able to improve rest and exercise haemodynamics, maintain its benefits when given orally and result in an improved exercise capacity and quality of life, and prolonged survival. PMID- 1888445 TI - Experimental orthotopic penetrating keratoplasty--a rat penetrating keratoplasty model. AB - An orthotopic penetrating keratoplasty model was developed in the rat. An oversized (0.5 mm) graft was used and 8 interrupted sutures were applied. These sutures were not removed. Eleven grafts out of 13 were rejected by the 3rd week in the disparate group (Brown Norway rat to Lewis rat transplantation group), which was characterized by edema, opacity, and neovascularization. All grafts remained clear in the syngeneic group (Lewis rat to Lewis rat transplantation group). Immunohistochemical examination was performed. This model seems to be a reliable and reproducible one to evaluate rejection reaction in corneal transplantation. PMID- 1888441 TI - Benzodiazepine poisoning. Clinical and pharmacological considerations and treatment. AB - Benzodiazepines are among the most frequently prescribed drugs worldwide. This popularity is based not only on their efficacy but also on their remarkable safety. Pure benzodiazepine overdoses usually induce a mild to moderate central nervous system depression; deep coma requiring assisted ventilation is rare, and should prompt a search for other toxic substances. The severity of the CNS depression is influenced by the dose, the age of the patient and his or her clinical status prior to the ingestion, and the coingestion of other CNS depressants. In severe overdoses, benzodiazepines can occasionally induce cardiovascular and pulmonary toxicity, but deaths resulting from pure benzodiazepine overdoses are rare. Quantitative determinations of benzodiazepines are not useful in the clinical management of intoxicated patients since there is no correlation between serum concentrations and pharmacological and toxicological effects. Benzodiazepine overdoses occurring during pregnancy rarely induce serious morbidity in mothers or fetuses, although large doses administered near delivery can induce respiratory depression in neonates. The teratogenic potential of benzodiazepines remains controversial, but is probably small if it exists at all. There is clear evidence that the prolonged use of even therapeutic doses of benzodiazepines will lead to dependence. The risk of developing significant withdrawal symptoms is related to dosage and duration of treatment. Prevention of gastrointestinal absorption should be initiated in all intentional benzodiazepine overdoses. Forced diuresis and dialysis techniques are not indicated since they will not significantly accelerate the elimination of these agents. Intravenous administration of flumazenil, a pure benzodiazepine antagonist, effectively reverses benzodiazepine-induced CNS depression. PMID- 1888446 TI - Assessment of regional cerebral blood flow (rCBF) in ischemic stroke using Tc-99m HMPAO SPECT--comparison with CT and MR findings. AB - To assess the regional cerebral blood flow (rCBF) in ischemic stroke, we analyzed the findings of single photon emission computed tomography (SPECT) using technetium-99m hexamethyl propyleneamine oxime (Tc-99m HMPAO). The SPECT images revealed abnormal areas of decreased perfusion in 29 out of 31 subjects (93.5%), which represented a higher detection rate than those for CT and MR (89.5%, respectively). Also, the areas of decreased perfusion were frequently larger than the lesions on CT and MR. Areas of decreased perfusion remote from the CT/MR lesions were found in 10 patients, including 8 with crossed cerebellar diaschisis (CCD). Thus, studies of rCBF by Tc-99m HMPAO SPECT can be useful in the assessment of ischemic stroke. PMID- 1888447 TI - Different modifying responses of capsaicin in a wide-spectrum initiation model of F344 rat. AB - The modifying potential of capsaicin (CAP) on lesion development was examined in a rat multiorgan carcinogenesis model. Groups 1 and 2 were treated sequentially with diethylnitrosamine (DEN) (100 mg/kg, ip, single dose at commencement), N methylnitrosourea (MNU) (20 mg/kg, ip, 4 doses at days 2, 5, 8, and 11), and N,N dibutylnitrosamine (DBN) (0.05% in drinking water during weeks 3 and 4). Group 3 received vehicles without carcinogens during the initiation period. Group 4 served as the untreated control. After this initiating procedure, Groups 2 and 3 were administered a diet containing 0.01% CAP. All surviving animals were killed 20 weeks after the beginning of the experiment and the target organs examined histopathologically. The induction of GST-P+ hepatic foci in rats treated with carcinogens was significantly inhibited by treatment with CAP. CAP treatment significantly decreased the incidence of adenoma of the lung but increased the incidence of papillary or nodular (PN) hyperplasia of the urinary bladder. The tumor incidence of other organs, such as the kidney and thyroid, was not significantly different from the corresponding controls. These results demonstrated that concurrent treatment with CAP not only can inhibit carcinogenesis but can also enhance it depending on the organ. Thus, this wide spectrum initiation model could be used to confirm organ-specific modification potential and, in addition, demonstrate different modifying effects of CAP on liver, lung, and bladder carcinogenesis. PMID- 1888448 TI - Incidence estimation of thyroid cancer among Koreans. AB - The medical records of inpatients with diagnoses of either ICD-9 193(malignant neoplasm of the thyroid gland) or 226(benign neoplasm of the thyroid gland) in the claims sent in by medical care institutions throughout the country, to the Korea Medical Insurance Corporation (KMIC) during the period from January 1, 1986 to December 31, 1987 were abstracted. These records were abstracted in order to identify and confirm new cases of thyroid cancer among the beneficiaries of the KMIC. Using these data, the incidence rate of thyroid cancer among Koreans was estimated as of July 1, 1986 through June 30, 1987. The crude rates were estimated to be 0.76(95% Cl: 0.63-0.87) and 3.87(95% Cl: 3.60-4.14) per 100,000 in males and females, respectively, and the cumulative rates for the age spans 0 64 and 0-74 in males were 0.06% and 1.10%, respectively. In females, those were equally 0.35%. The age-adjusted rate for the world population was 0.93 per 100,000 in males, which is one of the lowest levels in the world. However, the adjusted rate in females was 3.96 per 100,000, which is an average level and very similar to that of the Chinese in Singapore and Shanghai. A similar tendency was shown in the case of the truncated rates for the age group of 35-64, which was 1.91 per 100,000 in males and 8.82 per 100,000 in females. PMID- 1888444 TI - Risk-benefit assessment of anaesthetic agents in the puerperium. AB - A critical evaluation of anaesthetic agents in the puerperium is difficult because systematic, relevant studies are still lacking. Current knowledge of the effects of different agents used in labour and caesarean section indicates that significant residual effects on the mother and newborn are limited. In the early puerperium, based on physiological and/or hormonal changes, the mother could be more sensitive to inhalational anaesthetic agents and local analgesics. To date there is no evidence that any anaesthetic agent is excreted in breast milk in clinically significant amounts when given as a single dose. The only exception is perhaps in the case of very premature neonates whose mothers have had multidrug therapy before labour. Even then the importance of breast milk should be carefully assessed against possible adverse drug effect. However, repeated administration of long-acting benzodiazepines and continuous epidural administration of pethidine (meperidine) can have adverse effects on the neonate. The essential conclusion of this review is that breast-feeding is best. The different anaesthetic agents are excreted in the milk in amounts so low that detrimental effects on the neonate should not be expected. PMID- 1888449 TI - Production of tumor necrosis factor-alpha by alveolar macrophages from patients with pulmonary tuberculosis. AB - In order to ascertain the role of TNF-alpha in pulmonary tuberculosis, we determined the TNF-alpha productivity of alveolar macrophages(AMs) obtained by bronchoalveolar lavage(BAL), along with the level of TNF-alpha in the serum of patients with tuberculosis including pulmonary, miliary, and endobronchial tuberculosis, healthy controls, and pulmonary diseases such as diffuse interstitial lung disease (DILD) and pneumonia. AMs from patients with pulmonary tuberculosis did not produce a larger amount of TNF-alpha than did those from the healthy control subjects. However, among the patients with pulmonary tuberculosis, the AMs from the fresh and reactivated groups produced a larger amount of TNF-alpha than those from the inactive group. AMs from patients showing positivity in culture produced a larger amount of TNF-alpha than those showing negativity. The average level of serum TNF-alpha in patients with pulmonary tuberculosis was slightly higher than that of the healthy control group. Among patients with pulmonary tuberculosis, significantly increased levels of serum TNF alpha were noted in the reactivated group compared to those of the fresh and inactive group. Patients with moderate to far-advanced infiltration on their chest X-rays, showed a significantly higher level of serum TNF-alpha than those with minimal involvement on the chest X-ray. Smokers from the healthy control group showed a significantly higher level of serum TNF-alpha than non-smokers from the same group. These results suggest that an increase in the production of TNF-alpha may correspond with the severity of pulmonary tuberculosis. PMID- 1888450 TI - Necrotizing lymphadenitis--a clinico-pathologic study of 36 cases with immunohistochemical analysis. AB - Thirty-six cases of necrotizing lymphadenitis--including 33 cases of unknown etiology, 1 typhoid lymphadenopathy, and 2 cases of suspicious lupus lymphadenopathy--were clinico-pathologically reviewed and analyzed with immunostaining for s-100 and lysozyme. All cases histologically showed architectural effacement by paracortical lesions composed of nuclear karyorrhexis and mononuclear cell proliferation. Immunohistochemical study revealed proliferation of lysozyme-positive macrophages in the necrotizing areas and an increase in the number of s-100-positive cells in the uninvolved paracortical areas. This observation suggests that necrotizing lymphadenitis may be a common morphologic expression of a T cell-mediated hyperimmune condition induced by diverse etiologies. PMID- 1888451 TI - The prevalence of specific IgE and IgG to reactive dye-human serum albumin conjugate in workers of a dye factory and neighboring factories. AB - Previous studies suggest that reactive dyes can induce IgE mediated bronchoconstrictions. To evaluate the significance of specific IgE and IgG antibodies in workers exposed to reactive dyes, we studied the prevalence of Black GR-specific IgG by enzyme linked immunosorbent assay, as well as Black GR specific IgE by RAST, in 176 workers employed in 1 reactive dye factory and 4 neighboring factories. Six employees of reactive dye asthma who were working in factories near the reactive dye factories were noted. The prevalence of specific IgE antibodies in the neighboring factories was higher than in that of the reactive dye factory. The prevalence of specific IgG was highest in the reactive dye factory, and those of the neighboring factories were markedly lower. It was suggested that IgE mediated sensitization to reactive dye could have occurred in employees who were working in neighboring factories, and the prevalence of reactive dye-specific IgG antibody could be used as an in direct method of assessing the exposure of workers to reactive dye. PMID- 1888452 TI - Giant cell tumor of the scapula associated with secondary aneurysmal bone cyst. AB - Giant cell tumors are distinctive neoplasms characterized by a profusion of multinucleate giant cells scattered throughout a stroma of mononuclear cells. Most giant cell tumors are found at the epiphyses of long bones, especially around the knee joint. Flat bone involvement is rare. However, a case of giant cell tumor with secondary aneurysmal bone cyst was encountered at the scapula of a 25-year-old man. Since the occurrence of a giant cell tumor with secondary aneurysmal bone cyst on flat bones (i.e., the scapula) is extremely rare, the above-mentioned case is worthy of reporting. PMID- 1888453 TI - Incidence estimation of stomach cancer among Koreans. AB - A series of incidence estimation studies of cancers among Koreans through a nationwide survey has been undertaken by authors since 1988. The medical records were studied of inpatients with diagnoses of either ICD-9 151 (malignant neoplasm of the stomach), or 197 (secondary malignant neoplasm of the respiratory and digestive systems), or 211 (benign neoplasm of other parts of the digestive system) in claims sent in by medical care institutions throughout the country to the Korea Medical Insurance Corporation (KMIC) during the period from January 1, 1986 to December 31, 1987. These records were abstracted in order to identify and confirm the new cases of stomach cancer among the beneficiaries of the KMIC, which covers about 10% of whole Korean population. Using these data from the KMIC, the incidence patterns of stomach cancer among Koreans were estimated as of July 1, 1986 to June 30, 1987. The crude incidence rates of stomach cancer among Koreans are estimated to be 36.2 (95% tonfidence interval; 35.3-36.9) and 21.0 (95% CI; 20.3-21.6) per 100,000 in males and females, respectively. The cumulative rates for age spans 0-64 and 0-74 are 3.8% and 7.3% in males, respectively. In females they are 1.8% and 3.0%. The adjusted rates for the world population are 57.9 in males and 25.1 in females, which are similar to those of Shanghai, China '78-'82 but lower than those of Osaka, Japan. The truncated rates for ages 35-64 years, however, are 108.3 in males and 49.1 in females, which may be the highest in the world. Among Koreans in Korea, an increased risk of stomach cancer in this age group is the notable finding. Incidence patterns of stomach cancer by age, sex, and area, which are the first report in Korea, are analyzed and presented. PMID- 1888454 TI - Pulmonary lymphangioleiomyomatosis in a male. AB - Pulmonary lymphangioleiomyomatosis has been observed almost exclusively in women, usually in their reproductive years. Exacerbations with pregnancy and after hormonal manipulation have been documented, and it has been suggested that its pathogenesis is due to the influence of hormonal(estrogenic) stimulus. The clinical, roentgenographic, and histopathologic features of this case of pulmonary lymphangioleiomyomatosis in a 22-year-old male are all characteristic of those described in prior reports, except for the patient's sex. With the following case of pulmonary lymphangioleiomyomatosis in a male, we suggest the possibility of the existence of an additional pathogenetic mechanism. PMID- 1888455 TI - Alcoholic pellagra encephalopathy combined with Wernicke disease. AB - Clinical and postmortem findings of a case that had combined alcoholic pellagra encephalopathy and Wernicke disease are described. This 51-year-old malnourished and chronic alcoholic man presented with progressive mental deterioration, pellagra dermatitis, hypertonus of the neck and other musculatures, myoclonic jerks with bizarre involuntary movements, in addition to total external ophthalmoplegia and gait disturbance. After administration of multivitamins, including thiamine and nicotinamide, these neurologic abnormalities were dramatically improved in a few days. However, the patient died thereafter because of sepsis associated with pneumonia. Postmortem examination revealed marked abnormalities in CNS, characterized by diffuse atrophy of gray matter and widespread neuronal degeneration and characteristic central chromatolysis in pontine nuclei, dentate nuclei, cranial nerve nuclei in the brain stem, Betz cells of the cerebral cortex, and Clarke's column and anterior horn cells of the spinal cord. There were also atrophy and gliosis of the mammillary bodies, degeneration and vascular proliferation of periaqueductal gray matter, and massive gliosis around the third ventricle. These neuropathological changes were compatible with symptoms of both alcoholic pellagra encephalopathy and Wernicke's disease, but they were also strongly suspected on clinical grounds. PMID- 1888456 TI - [Possible mechanism of production of the musical second heart sound and its clinical significance]. AB - To investigate the predisposing factors and the clinical significance of the musical aortic component of the second heart sound (musical S2), 18 patients with musical S2 (musical group) among the consecutive 2,000 patients with phonocardiographic examination were noninvasively studied by analyzing underlying diseases, phonocardiographic findings, organic changes of the aortic valve, severity of aortic regurgitation and left ventricular dysfunction. Organic changes of the aortic valve were assessed by two-dimensional echocardiography, and aortic regurgitation was assessed by color Doppler flow imaging. Twenty-two normal subjects (normal group) and 17 patients with essential hypertension (hypertensive group) served as controls. Mean ages were matched among the three groups. 1. Left ventricular dilatation (seven patients) and hypertension (six patients) were the dominant part of underlying disease in the musical group. 2. Musical S2 was classified in the following two types based on the phonocardiographic characteristics; musical vibrations followed immediately after the accentuated S2, and the S2 which was replaced by regular vibratory waves. 3. Frequency of the musical vibrations ranged from 120 to 200 Hz, and its duration ranged from 60 to 120 msec. Amplitude of the musical vibrations decreased by inhalation of amyl nitrite, but increased by infusion of methoxamine. In a case with mild rheumatic valve disease, methoxamine induced marked intensification of the amplitude and prolongation of the duration of the musical vibrations, finally giving a typical cooing murmur. 4. Echo intensity of the aortic valve tended to be higher in the musical group than in the other two groups. 5. Echocardiographically, aortic regurgitation appeared more frequently in the musical group (88%) than in the normal (36%) and hypertensive (41%) groups. Area of the aortic regurgitant signal was significantly larger in the musical group (4.1 +/- 1.4 cm2) than in the normal (1.2 +/- 0.8 cm2) and hypertensive (2.3 +/- 1.2 cm2) groups. 6. Left ventricular end-diastolic dimension was significantly larger in the musical group (5.8 +/- 0.6 cm) than in the normal (4.7 +/- 0.5 cm) and hypertensive (4.8 +/- 0.7 cm) groups. Fractional shortening of the left ventricle was significantly smaller in the musical group (26 +/- 10%) than in the normal (37 +/- 5%) and hypertensive (37 +/- 8%) groups. In a case of the musical group, musical vibrations following the S2, which was large in amplitude at the state of heart failure, decreased markedly after the recovery from heart failure.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1888457 TI - [Transesophageal echocardiographic study on systolic flow pattern of the pulmonary vein in patients with mitral stenosis and atrial fibrillation]. AB - To determine the clinical significance and effect of cycle length on systolic backward (C) and forward (S) flow patterns of the pulmonary vein, we performed transesophageal and transthoracic echocardiography in patients with atrial fibrillation (Af). Study population consisted of 10 patients with mitral stenosis and sinus rhythm (MS-SR), 15 with MS and Af (MS-Af), 15 with mitral valve replacement and Af (MVR-Af), 10 with Af without organic heart disease (lone-Af) and 15 normal subjects. Various parameters, including peak velocities of C and S waves, closing amplitude of anterior mitral valve echogram during end-diastole, amplitude of the mitral annulus and interatrial septal motion during systole and left atrial pressure during the mitral closing period or end-diastole, were measured in each group. Results were as follows: 1. C wave was observed in all Af groups and six of 10 patients with MS-SR. Particularly, peak velocity of the C wave in MS-Af group was increased significantly compared with those of every other group. 2. Peak velocity of S wave in all Af groups, particularly in MS- and MVR-Af groups, decreased significantly compared with that of the normal group. 3. There were significant negative correlations between preceding R-R interval and peak velocity of the C wave or closing amplitude of anterior mitral valve echogram or left atrial pressure during end-diastole in MS-Af group. 4. There were significant positive correlations between preceding R-R interval and peak velocity of the S wave or amplitude of the mitral annulus or interatrial septal motion during systole in MS-Af group. 5. Peak velocities of the C and S waves had no correlations to preceding R-R interval in lone-Af group. We concluded that the C and S waves of pulmonary venous flow velocity pattern in MS-Af are affected by cycle length, and that the former is influenced by left atrial pressure and/or pliability of the mitral valve during the mitral closing period, and the latter by the grade of left atrial dilatation and/or preceding left atrial emptying. PMID- 1888458 TI - [Diagnosis of prosthetic mitral valve regurgitation by Doppler color flow imaging using right parasternal approach: a comparative study with transesophageal method]. AB - Doppler color flow imaging is a useful tool in evaluating mitral regurgitation (MR). However, it is frequently difficult to assess prosthetic valve MR by the conventional transthoracic approach using left parasternal or apical echo windows, because of the interception of ultrasound by the prosthesis or artifacts produced by its motion. The purpose of this study is to determine the usefulness of the "right" parasternal approach (RPA) in the echo diagnosis of prosthetic MR. Six patients with pathological prosthetic MR determined by transesophageal approach (TEA) were studied. Transthoracic echo was performed using both the RPA and the conventional approach, and the presence or absence and the extent of MR signals by these transthoracic approaches were compared with those by TEA. Prosthetic MR was detected in five of six patients by the RPA and the extent of MR signals by the RPA was very similar to that by TEE in each of the five patients. MR could not be detected by the RPA only in one patient, whose MR was estimated to be very mild by TEE. By the conventional approach, MR could not be detected in three patients and the degree of MR was significantly underestimated in two of the remaining three patients. Thus, the transthoracic RPA is often as useful as TEA in diagnosing prosthetic MR, which is often undetectable or underestimated by the conventional approach. Because the RPA is less invasive than TEA, the RPA should be encouraged in patients with suspected prosthetic mitral valve dysfunction. PMID- 1888459 TI - [Development of severe mitral regurgitation following percutaneous transvenous mitral valve commissurotomy]. AB - The purpose of this study was to analyze the risk factors of unexpected occurrence of mitral regurgitation (MR) following percutaneous transvenous mitral valve commissurotomy (PTMC) in patients with mitral stenosis. The analyzed factors were clinical pictures, hemodynamic findings, echocardiographic findings and balloon inflation techniques during PTMC. Among 24 patients undergoing successful PTMC using an Inoue's balloon, severe MR developed in five patients (21%). No significant correlation in the occurrence of MR was observed in clinical findings, hemodynamic data and balloon inflation techniques including the times and size of ballooning. Echocardiographic findings of the mitral valve including the pliability of the mitral leaflet and localized calcification of the mitral orifice were the most contributory factors to the occurrence of severe MR. The localized alternation of valve stiffness produced localized tear or excessive dilatation of the mitral leaflet during PTMC, resulting in severe MR. Hemodynamic results and calculated mitral valve areas after PTMC showed significant improvement in both groups with and without MR. However, symptomatic improvement in patients with severe MR was less prominent when compared to the patients without MR. Thus, the complete echocardiographic evaluation of the mitral valve apparatus before PTMC is important to prevent severe MR. PMID- 1888460 TI - [Doppler hemodynamic evaluation of bioprosthetic valve failure in the mitral position]. AB - M-mode and two-dimensional echocardiography (2DE) allows the accurate assessment of primary tissue degeneration of bioprosthetic valves. The Doppler method permits quantitative evaluation of the pressure gradient across the prosthetic valve or detection of regurgitant flow. The present study summarized our clinical experiences of serial cases of mitral valve replacement (MVR) with bioprostheses at the mitral position, and clarified the clinical usefulness and limitations of Doppler and 2DE examinations for the early detection of primary valve dysfunction. Consecutive 65 patients undergoing single mitral valve replacement from April, 1977 to November, 1979 were listed for the study. A survey of the present clinical status was carried out from July, 1988 to July, 1990 (a follow up period ranged from 84 to 127 months) for all patients, and the information was available from 53 patients (47 adults and six infants). Twenty-four survived patients without re-MVR were examined by Doppler and 2DE. Among the 53 patients, 34 were alive and 19 dead, and the total survival rate was 64.2%. The reasons for death in 19 patients were perioperative death in seven (including four infants with severe calcification of bioprostheses), chronic heart failure in three, cerebral infarction in two, post blood transfusion hepatitis in two, endocarditis in one, and non-cardiac death such as cancers in four. During the long-term observation of 47 adult patients, 14 cases (30%) had re-MVR (one for a stenotic lesion with massive calcification, and 13 for torn leaflets). Thickening and/or torn leaflets were noted in 13 (54%) of the 24 survived patients without re MVR.2+ suggests that bioprosthetic valve replacement at the mitral position may not be recommended. PMID- 1888461 TI - [Four boys with multiple floppy valves involving all cardiac valves and hyperextensive joints]. AB - We experienced four boys (two siblings) whose cardiac valves were all prolapsed, which have never been reported as a recognized disease. All had hyperextensive joints without any other stigmata of Marfan or Ehlers-Danlos syndrome. The severity and progression of regurgitation of each valve differed by a case, though they had similar echocardiographic findings consistent with the diagnosis of multiple floppy valves. Three of the four patients had severe aortic regurgitation, and two received aortic valve replacement. Their excised valves revealed myxomatous degeneration. The tricuspid valves were more thickened and redundant than the mitral valves. Although three patients had moderate tricuspid regurgitation, none of them had clinically important mitral regurgitation. We recommend aortic and/or mitral valve replacement, whenever the regurgitation exacerbates left ventricular dilatation. Aortic regurgitation deteriorated rapidly in one case due to valve rupture. In this case, moderate tricuspid regurgitation was relieved after aortic valve replacement. Skin fibroblast did not show any abnormalities in collagen biosynthesis. PMID- 1888462 TI - [Mitral valve disease with pulmonary hypertension: two surgical cases]. AB - Two surgical cases of mitral valve disease with severe pulmonary hypertension were reported, in which pulmonary hypertensive crisis (PHC) was a really serious problem to be treated. The first case (60-year-old woman) had atrial fibrillation and her pulmonary artery pressure was 68/32 mmHg (Pp/Ps = 0.63) and mean pulmonary wedge pressure was 26 mmHg with a high v wave (46 mmHg). PHC developed immediately after the cessation of artificial cardiopulmonary bypass, and intraaortic balloon pumping was performed. However, it was difficult to wean from the assist circulation, and then PGE1 and isoproterenol were given into the pulmonary artery and epinephrine and norepinephrine were given into the left atrium, and we succeeded in weaning from the assist circulation. The second case (58-year-old woman) had high pulmonary artery pressure (86/37 mmHg) and the Pp/Ps was 0.73. According to the experience of the first case, prevention of PHC started during cardiopulmonary bypass, giving PGE1, nitroglycerin and torazoline into the pulmonary artery. This led to the easy weaning from cardiopulmonary bypass. PHC may be seen even in cases of acquired valvular disease, and the prevention is mandatory for uneventful surgery. PMID- 1888463 TI - [Mycotic aneurysm of the sinus of Valsalva and complete atrioventricular block complicating infectious endocarditis with aortic regurgitation: a case report]. AB - A patient with a mycotic aneurysm of the sinus of Valsalva and heart block secondary to infectious endocarditis was described. This 46-year-old man was admitted to our hospital on May 9, 1990, because of fever and progressive general malaise after extraction of a tooth. Physical examination on admission revealed blood pressure of 98/62 mmHg, pulse rate 96 per min, temperature 37.7 degrees C and respiration 35 per min. Auscultation of the heart revealed a grade 3/6 systolic murmur and a grade 2/6 diastolic murmur at the third left intercostal space. Chest radiograph showed mild cardiomegaly with moderate lung congestion. Electrocardiography revealed the first grade atrioventricular block. Echocardiography demonstrated vegetations on the aortic valve, and perforation of the non-coronary sinus of Valsalva. The prolapsed non-coronary sinus of Valsalva extended into the right atrium. Doppler echocardiography revealed a severe aortic regurgitant jet in the diastolic phase. We diagnosed the patient as having aortic regurgitation with a mycotic aneurysm of the non-coronary sinus of Valsalva due to infectious endocarditis. His condition remained severely ill despite intensive medical treatment. On May 14, 1990, aortic valve replacement and excision of the mycotic aneurysm were performed. The commissural portions of the aortic cusps were heavily thickened and calcified. The mycotic aneurysm was very fragile. During manipulating the mycotic aneurysm, the sinus accidentally perforated into the right atrium. The cardioaortic fistula was closed with a goretex patch. A demand pacemaker was implanted because of postoperative complete atrioventricular block.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1888464 TI - Aspects of mitral and tricuspid regurgitation. PMID- 1888465 TI - [Pathology of the cardiac valves]. AB - The cardiac valves develop from the endocardial cushions of the fetus. Some congenital anomalies such as the 21-trisomy syndrome (Down syndrome) show poorly differentiated immature valves similar to those under development. The normally mature valves have four layers of the connective tissue, i.e., proximalis, spongiosa, fibrosa and distalis. Gargoylism promotes abnormal thickening of collagen fibers in the fibrosa via acid-mucopolysaccharide (aMPS) overproduction, but Marfan syndrome weakens the valves in spite of increased aMPS. The reversed conditions could be caused by the difference of increased aMPS; i.e., dermatan sulfate B or heparitin sulfate in gargoylism, on the contrary, dermatan sulfate A and C or hyaluronic acid in Marfan syndrome. Hemodynamic changes in the valves consist of diffuse hypertrophy of the proximalis and fibrosa in high flow cases and focal thickening of the proximalis at the line of closure and of the spongiosa at the anatomical edge in high pressure cases. Aging of the valves simulates partly the hemodynamic changes but degeneration of collagen fibers in the fibrosa after consumption of the spongiosa is more prominent than the latter. So-called myxomatous degeneration in the mitral valve prolapse cases seems reactive hypertrophy of the spongiosa replacing the interrupted fibrosa. Spontaneous chordal rupture is partly related to myxomatous change, but that in the elderly cases shows only simple disruption of collagen fibers with loss of the spongiosa tissue. Calcification of the valvular rings and bodies often observed in the elderly cases with parallelism to degeneration of the connective tissue produces mitral regurgitation, aortic stenosis or both, showing a preponderance of females.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1888466 TI - [Physiology of the heart valves]. AB - The function of healthy heart valves has been understood as the "on-off switch", which initiates and terminates blood flow in the cardiac cycle. It is believed that an impedance of the valves against blood flow is minimal and their closure is abrupt and complete. Clinically, an increase in impedance of the diseased valve is estimated by measuring pressure difference across that valve. However, the pressure gradient induced by acceleration of blood along the outflow tract of the ventricle or the artery during the early ejection phase, or along the inflow tract of the ventricle during the rapid filling phase can not be estimated separately from the pressure difference produced by valvular impedance in physiological state. Opening speed of the valve is related to the factors determining the velocity of blood flow. Mechanisms of a valve closure have been explained based on the Henderson and Johnson's concepts. Recent advances in ultrasonic technology can only confirm their concepts. Measurement of the pressure gradient across the semilunar valves in the late ejection phase has also several technical difficulties. Relationships among pressure, flow and valve motion have been extensively investigated, how-exact determination of the timing of the valve closure is not detected. The heart valves are considered to function as a passive organ throughout the cardiac cycle except for the atrioventricular valves including the subvalvular apparatus during systolic phase. The development of new methodology is necessary for the investigation of this field. PMID- 1888467 TI - [Morphological observation of the mitral annulus fibrosus (II)]. AB - In 1986, Hutchins observed a high incidence of the disjunction of the mitral annulus fibrosus in mitral valve prolapse syndrome. However, we could not prove his view in our previous study using one section in each case. In this study, the types of mitral annulus fibrosus were analyzed in plural sections. Autopsy hearts of nine aged cases were used for examination of the mitral annulus fibrosus in five to eight longitudinal sections from the posterolateral wall. The types of the mitral annulus fibrosus were classified as; Type A (the mitral valve attaches to the left ventricle), Type B (the valve attaches to the left atrium), Type C (the atrialis layer of the valve continues to the left atrium, while the fibrosa layer continues to the left ventricle), and type D (mitral annulus calcification). A1-3 and B1-3 are subtypes. In the nine cases there were no consistent patterns in type distributions. All sections showed Type A1 (Case 2), Type A1 to A3 (Case 5), and Type B1 to B3 (Case 8). In other cases, a combination of Type A and B (Case 4, 6, 7, 9), and inclusion of Type C (Case 1) and Type D (Case 3) were found. The location of the middle scallop of the posterior mitral leaflet corresponded to the section of the previous study. Among three cases of Type A in the middle scallop, two showed Type A in every section. Among five cases of Type B in the middle scallop, only one case showed Type B in every section. Other four cases showed various combinations with the other types. A case of Type D in the middle scallop showed also Type B and Type C. The conclusion of this study was that in 1/3 of the cases, the type of the mitral annulus fibrosus was consistent, but in the other 2/3 they were not consistent. In other words, one section is not necessarily representative of the morphology of the mitral annulus fibrosus in each case. PMID- 1888468 TI - [The prevalence and clinical features of pathologically abnormal mitral valve leaflets (myxomatous mitral valve) in the mitral valve prolapse syndrome: an echocardiographic and pathological comparative study]. AB - We studied the prevalence and clinical features of pathologically abnormal mitral valve leaflets (myxomatous mitral valve: MMV) in consecutive 142 patients with the mitral valve prolapse syndrome (MVP). Our echocardiographic criteria for MMV were 1) thick leaflets 3 mm or greater, 2) redundant leaflet-motion, and 3) echo density lower than that of the aortic walls. The echocardiographic measurements of left ventricular diastolic dimensions (LVDd), percent fractional shortening (%FS), mitral annular diameter (MAD), and LV mass were compared between MMV and non-MMV groups. Twelve patients (8%) were referred for surgery because of congestive heart failure, and two patients died during the observation periods. Gross morphology of the MMV was characterized by increased surface area, dome formation of the leaflet-body, and non-uniform leaflets in thickness, and histologic findings of the MMV were the infiltration of spongiosa layer into the fibrosa layer. The diagnostic accuracy of echocardiography for the MMV was examined in 14 patients underwent either surgery or autopsy, and it was high (78% in sensitivity and 80% in specificity). The progression of mitral regurgitation (MR) from mild to moderate grade or mild to severe grade was found in five of 26 patients during follow-up studies over 12 months (mean = 36 months). All of the five patients were aged 50 years and older. While, MR completely disappeared in a 17-year-old boy with marked physical development within three years of the observation period. Mitral annular diameter significantly increased in MMV with MR when compared to non-MMV with MR (4.1 +/- 0.7 vs 3.5 +/- 0.4). But no significant changes were noted in LVDd and LV mass between non-MMV with MR and MMV with MR. Of the 142 patients with MVP, 96 patients were non-MMV and 46 patients were MMV. Ruptured chordae tendineae were associated in 5/96 patients (5%) with non-MMV and 22/46 patients (48%) with MMV. Intracardiac vegetations were seen in four of the 96 patients (4%) with non-MMV. The prevalence of MMV in MVP was greater in older patients, and it reached nearly as high as 50% of MVP patients aged 60 years and older. In conclusion, the echocardiographic diagnostic criteria for MMV are reliable with high sensitivity and specificity, and are useful to predict the high risk patients in the MVP syndrome. MMV may be a potential etiology causing aggravation of mitral regurgitation and/or ruptured chordae tendineae. PMID- 1888469 TI - [Clinical survey of 126 cases with mitral valve prolapse detected at the annual health check-up]. AB - Clinical and echocardiographic survey of mitral valve prolapse (MVP) was performed in 616 cases, which were selected from about 6,000 health check-up. An echocardiographic study revealed MVP in 126 cases. The prevalence of MVP was about 2% (health check-up survey) and 20.5% (echo study). The male and female ratio was 102/24. Frequent premature contractions, isolated atrial fibrillation and an apical systolic murmur were more frequently associated with MVP. Among 13 cases of isolated atrial fibrillation, seven with MVP were permanent, while other six without MVP were transient. Most cases (77%) were asymptomatic. Mild mitral regurgitation proved by auscultation and phonocardiography was observed in only two cases (1.6%), and most of the cases (81%) had no mitral regurgitant signals by a Doppler study. PMID- 1888471 TI - Models in the biological sciences. PMID- 1888470 TI - [Mitral regurgitation due to redundant chordae]. AB - This paper reports the etiology and the findings of phonocardiograms and echocardiograms in four cases with mitral regurgitation caused by the redundant chordae. Redundancy of the chordae were determined by the surgeon during operation. The results were as follows: 1. The etiology of redundant chordae was either congenital, rheumatic, or mucoid degeneration. 2. Phonocardiographic findings of this condition are a holosystolic murmur accompanied by a diastolic rumble at the apex. 3. Two-dimensional echocardiogram shows holosystolic bulging of the mitral leaflet to which redundant chordae are attached. 4. The findings of the M-mode echocardiogram are multiple linear echoes and bowing of the mitral valve in systole. PMID- 1888472 TI - [Use of DNA amplification by PCR in the study of the hypervariable region (VNTR) in a forensic medicine setting. Experience with 2 systems: Apo B and YNZ 22]. AB - The PCR method has been applied to amplify two Variable-number-Tandem-Repeat (VNTR) sequences. The high polymorphism of these VNTR systems can be usefully applied in medical legal fields such as paternity testing and individual identification. The VNTR systems utilized were: ApoB and YNZ 22. The study was conducted on a three-generation family of thirteen members, whose relationship was previously established using conventional blood systems. The results confirm the Mendelian inheritance of the alleles found and the suitability of the PCR method for forensic purposes. PMID- 1888473 TI - Functional properties of Hb-J Calabria, beta 64 (E8) Gly-Asp. AB - A young male from Apulia region (Southern Italy), heterozygous carrier of Hb-J Calabria (beta 64(E8) Gly-Asp), was described here. He showed mild polycythemia, and his whole blood dissociation curve for oxygen was clearly left-shifted, with a decreased p50. But these characteristics were not only due to the hyperaffinity of the abnormal pigment, accounting for about one third of the total Hb; in fact, also Hb-A, the main pigment present, had relative hyperaffinity. Nevertheless, this subject was completely symptomless, suggesting that the abnormal Hb was almost completely excluded from respiratory exchange and traveled always oxygenated also in the venous-capillary bed. However, the level reached by Hb-A furnished a satisfactory functional compensation against tissue hypoxia. PMID- 1888474 TI - EEG changes and platelet aggregation in experimental cerebral focal ischemia in rabbits. AB - Nine white New Zealand rabbits were submitted to internal carotid embolization with microspheres which caused a histologically verified focal cerebral ischemia. Six animals were sham-operated. EEG, QEEG, ECG, blood pressure, rectal temperature and platelet aggregation were monitored in basal conditions and one hour after ischemia. Embolized animals showed an increase in power density spectrum (PDS) and delta activity (0.15-3.70 Hz) and the appearance of platelet aggregation. The QEEG changes were correlated to the degree of platelet aggregation after ischemia. PMID- 1888475 TI - Prestimulus EEG influence on late ERP components. AB - Ten healthy volunteers were submitted to an auditory oddball event related potentials (ERP) paradigm. Single trial 500 ms poststimulus ERPs (Pz, Cz, Fz- linked earlobes) along with the correspondent 1000 ms prestimulus EEG (O1-Cz) were stored. EEG epochs were submitted to spectral analysis and a slow wave index (SWI = delta + theta/total) was computed. Three selective ERP averages corresponding to low, medium and high SWI were computed. N2 latency was longer and P3a amplitude was lower in high SWI averages as compared to low SWI averages. PMID- 1888476 TI - Effect of repetition rate on middle latency auditory evoked potentials in humans. AB - Middle Latency Auditory Evoked Potentials (MLAEPs) were recorded from 15 healthy subjects in order to evaluate the influence of different repetition rates on the latency and the amplitude of their main components Na, Pa and Nb. MLAEPs were obtained from Cz-ipsilateral ear lobe by averaging responses to 2000 monaural clicks delivered to both ears, at 65 dB SL of intensity, for each of 3 different repetition rates (1.1, 4.1, 8.1 Hz). Time base was 100 ms, analogical band-pass filter 5-1000 Hz (off-line digital bandpass: 20-100 Hz). The statistical analysis (repeated measures analysis of variance), demonstrated that, the latency and the amplitude of the Nb component were slightly influenced by repetition rate while Pa and Na were not. Moreover Nb showed the greatest interindividual variability (as already pointed out by other authors too); thus, we suggest that a stimulus rate of 8.1 Hz and the analysis of Na and Pa component only, can be regarded as the best assessment for MLAEPs evaluation when they are used for clinical purposes. PMID- 1888477 TI - [Inflammatory process caused by intraperitoneal injection of polyester in the rat: chemotactic activity in lavage fluid from the cavity]. AB - Minced polyester threads introduced into peritoneal cavity of guinea pigs or rats cause a granulomatous inflammation with evidence of macrophage stimulation. Chemotactic agents play an important role in the inflammatory reaction; they may be exogenous and/or endogenous. These are released locally by the cells involved in inflammation. In this paper the chemotactic effects of the peritoneal fluids from rats bearing the polyester inflammatory process, have been studied on PMN cells "in vitro". The peritoneal cavity fluids were obtained by washing the cavity of untreated rats or rats intraperitoneally injected with polyester, 1, 3, 7, 14 days after the intraperitoneal injection. The chemotactic response was assayed by employing modified chemotaxis Boyden chambers (Blind Well Neuro Probe) and polymorphonuclear leukocytes from normal or treated rats. Quantification of the migration was calculated by chemotactic index (A/B) (B = random migration, A = chemotaxis). The results demonstrated that the peritoneal fluids taken 3 and 7 days after the intraperitoneal polyester injection, elicit an evident chemotaxis response greater than that showed by peritoneal fluids from control rats. It is suggested that chemotactic factors can be produced and released by mononuclear cells involved in the inflammatory process. PMID- 1888478 TI - [Chemotactic activity of the peritoneal lavage fluid of guinea pigs with inflammatory processes caused by the inoculation of various types of suture thread]. AB - Minced non adsorbable or adsorbable suture threads introduced into peritoneal cavity of guinea pigs elicit at inflammation with mononuclear and giant cells surrounding suture thread fragments. We studied the presence in the peritoneal cavity of chemotactic factors for PMN cells and we compared the results in relation to the different type of the suture threads used (Dexon, Mersilene, Gore Tex). The peritoneal cavity was washed, the fluids collected and used as chemotactic agents. The chemotactic response was assayed by employing multiwell chemotaxis chambers (Neuro Probe) and PMNs from normal, non-treated guinea pigs. Quantification of the migration was calculate by chemotactic index (A/B) (B = random migration, A = chemotaxis). The results demonstrate that a chemotactic activity is present in peritoneal fluids following the inflammatory process. This activity is evident at 7th day after Dexon and Mersilene inoculation; using PTFE however, it decreases at 14th d, when the inflammatory process is already developing into healing tissue. In conclusion the chronic inflammation determines the appearance of chemotactic factors for PMN cells; it is suggested that reactive, mononuclear cells, involved in the process, could be responsible for their production and release. PMID- 1888479 TI - [Morpho-histochemical observations on the liver parenchyma of adult albino rats subjected to acute acoustic stress]. AB - The hepatic noradrenergic innervation and the glycogen cellular content, after acoustic stress, were studied by the fluorescence and P.A.S. methods, respectively, in 7-month-old male albino rats exposed to continuous intense noise for 60' and 8 hours. While the 60'-treatment did not cause noteworthy changes in adrenergic fibers and a decrease in PAS-positive material, the 8 h.-treatment induced a significant increase of catecholamines content, in addition to a non homogeneous response to PAS reaction by hepatocytes surrounding the portal spaces or the lobular central veins. The authors ascribe the effect of the 8 h. treatment to a partial adaptation of hepatocytes to acoustic stress. PMID- 1888480 TI - [SEM study on the mucosa of the pre-stomach in Bubalus buffalus]. AB - Morpho-structural features of pre-stomach mucosa in the first period of post natal life in Bubalus buffalus have been studied by SEM. The rumen presents a well defined morpho-structural architecture from 10 to 100 days of life, while in reticulum and in omasum numerous morphological variations have been noticed. During the development, in fact, in these organs the establishment of a typical morphological pattern has been observed. PMID- 1888481 TI - [Role of Corollospora maritima in the degradation and bioconversion of leaf material from Posidonia oceanica]. AB - Posidonia oceanica supports mainly saprophytic marine flora, comprising predominantly lignicolous fungi. The frequency of occurrence of species recorded on this marine angiosperm, was high, indicating that they play a major role in the biological degradation of the sea grass Posidonia oceanica. In vitro experiments with Corollospora maritima (isolated from leaf material) were conducted in order to evaluate their role in the degradation of leaf material. Corollospora maritima actively degrade leaf material. Biophysical and biochemical changes (particle detritus formation, C and N variation), enzymatic activity involved and sterol production were studied during the transformation process of leaves to mycelial biomass. PMID- 1888482 TI - [Changes in the subendothelial compartment during the maturation process of cerebral microvessels]. AB - Basement lamina and pericytes of growing blood microvessels were analyzed in the chick embryo optic tectum, from the 8th incubation day to hatching. Formation of the basement lamina and morphological changes of the pericytes take place in a short range of time, but late in the embryonic life, when also the blood brain barrier (bbb) devices are developing. The spatial and temporal coincidence between basement lamina formation, endothelium tight junction differentiation, and perivascular arrangement of the astrocytic glia, indicates that these events are correlated and corroborates the hypothesis that the glia needs an extracellular matrix to induce the junctional system maturation in the neural endothelia. Pericytes are irregular in shape during the early neural angiogenesis and smooth and flattened later, as the basement lamina synthesis is taking place; these cells represent a second line of barrier beyond the endothelium when the bbb is immature, owing to their phagocytic and digestive properties. PMID- 1888483 TI - [Endothelial vesicles as a transport system in the blood-brain barrier. Morphometric study during development]. AB - The vesicles and vacuoles of the endothelia, morphological expression of endocytosis and transendothelial transport, are quite absent in the mature neural endothelia. In order to study the temporal sequence of the vesicle and vacuole modifications during the blood brain barrier (bbb) setting up, the extent of these structures was morphometrically analyzed on electron micrographs of neural microvessels in the optic tectum of 8, 14, and 17 day chick embryos, fixed after an intracardial injection of the permeability marker horseradish peroxidase. During the development, endocytosis and transendothelial transport change, since a statistically significant reduction of both vesicles and vacuoles was recorded at the 17th incubation day. The temporal coincidence between decrease of endocytosis-transport processes and appearance of astrocytic endfeet close to the vessel wall, suggests that the glial cells might control, besides the tight junction formation, the expression of other properties of the bbb-provided endothelia. PMID- 1888484 TI - Analytical morphometry of sagittal fronto-facial profiles of 2nd-6th month human foetus. AB - A prominent problem in the morphological study of developing biological structures is shape parametrization with the aim to evaluate transformations in a non subjective way. We carried out an analytical morphometrical study on a series of human embryos, by means of the S.A.M. (Shape Analytical Morphometry) software package. After standardization and normalization of the fronto-facial sagittal profiles, the analytical procedures applied were: 1) Fourier analysis: each profile was considered as an irregular but periodic function obtained by the sum of sinusoids of increasing order. 2) Shape Asymmetry Evaluation: couples of profiles are compared by means of "Janus" procedure; by a parabolic fitting we obtained parameters able to evaluate allometric and isometric differences between the two profiles. The preliminary results of the applied procedures indicated that rate and direction of allometric and isometric growth are not constant during the time. PMID- 1888485 TI - [Effect of the sudden removal of lambs on the blood levels of prolactin, triiodothyronine and thyroxine in ewes]. AB - The effect of the sudden removal of lambs, average age 42 days (36 to 54), on the blood level of PRL, T3 and T4 was checked, using a radioimmunological method, in 18 Sardinian ewes that had lambed in November (10 treated and 8 control). The two groups of animals, reared indoors in different sheep-folds, were subjected to the same management and feeding. Compared to day before the removal of the lambs, the blood PRL showed a sharp decrease which lasted 24 hours. After 4 days of observation, despite two daily milkings, the blood PRL had not returned to the initial levels. On the other hand, T3 and T4 showed an increase that lasted 48 hours, on the third day returning to the initial levels. PMID- 1888486 TI - Multivariate analysis of metastasis risk in laryngeal carcinoma. I. Tumor factors. AB - A multivariate analysis with a logistic regression model was performed in 181 cases of patients affected by laryngeal cancer, in order to evaluate the histologic tumor factors in predicting metastatic risk. The patterns used were: grading, localization, extension to the extralaryngeal structures, mode of growth. Nodal metastases are less influenced by the localization and the differentiation grade of the tumor. Cancer extended to the extralaryngeal tissues and with "infiltrating" type of growth are significantly correlated with nodal involvement. Multivariate analysis seems to be the best method to identify the exact value of each histological parameter used in prognosis of laryngeal carcinoma. PMID- 1888487 TI - Multivariate analysis of metastasis risk in laryngeal carcinoma. II. Immune response. AB - The presence of inflammatory reaction, plasma cells, and eosinophils in peritumoral connective tissue and in neoplastic stroma was evaluated with morphometrical method in 181 patients affected by laryngeal carcinoma. A logistic multiple regression model was applied making it with the use of an independent variable represented by the "infiltrating" or "expansive" types of tumor growth, in order to evaluate the probability of nodal metastatsis of each parameter. The results suggest an inverse correlationship between plasma cells and inflammatory infiltration and incidence of nodal metastatsis only in the comparison of the extreme conditions: those with scarce infiltration versus the ones with large infiltration. Inflammatory or plasmacellular infiltration may represent both a defense mechanism against cancer and an aspecific or allergic reaction. The eosinophilic infiltration shows no value in the prevention of nodal involvement. PMID- 1888488 TI - The quantitation of rabies-specific antibodies. III. A comparative evaluation of modified counter immunoelectrophoresis, haemagglutination inhibition and serum neutralization titres of human sera. AB - The rabies-specific antibodies of 73 serum samples from vaccinated humans were determined by the modified counter immunoelectrophoresis (MCIE), and the haemagglutination inhibition test (HAI) by using the conventional serum neutralization test (SN) as a yard-stick. Both MCIE and HAI were found to be sensitive and specific for the estimation of rabies antibodies. In general, the unitages obtained by the MCIE and SN showed statistically insignificant differences (P greater than 0.05) and the correlation coefficient between the two methods was 0.697 (P less than 0.05). Although the unitage of the sera detected by HAI tests was lower by a factor of 0.155 from the unitage of SN tests, there was statistically insignificant differences between the two techniques (P greater than 0.05) with a correlation coefficient of 0.556 (P less than 0.05). PMID- 1888489 TI - A collaborative assay of the proposed third British Reference Preparation for Pertussis Vaccine and of the relative potencies of the second International Standard and the second British Reference Preparation for Pertussis Vaccine. AB - A collaborative assay has been carried out to estimate the mouse protective potency of a freeze-dried preparation of Bordetella pertussis (88/522) intended to serve as the third British Reference Preparation for Pertussis Vaccine (third BRP). The opportunity was also taken of reassessing the relationship between the second International Standard for Pertussis Vaccine and the second British Reference Preparation for Pertussis Vaccine (second BRP). Workers in nine laboratories took part in the study and together completed 19 assays which were considered to be statistically valid. Based on the results of the study it is proposed that ampouled preparation code number 88/522 be established as the third BRP with an assigned potency of 50 IU per ampoule. The evidence of this study also suggests that the relationship between the second International Standard for Pertussis Vaccine and the second BRP has not changed significantly since they were originally established. PMID- 1888490 TI - Appraisal of rabies vaccine potency by determination of in vitro, specific interleukin-2 production. AB - The potency of different rabies vaccines was measured via cell mediated immunity (CMI) assessed by the production of interleukin-2 (IL-2) by CD4+CD8- lymphocytes. IL-2 production by splenocytes from mice immunized with various vaccines was measured following in vitro stimulation with antigens from different rabies and rabies-related strains. IL-2 production was specific, reproducible and correlated with the vaccine protective activity as determined by the pre-exposure NIH test. Our results suggest that measurement of IL-2 production could be used for the appraisal of rabies vaccine potency. PMID- 1888491 TI - Note for guidance. Production and quality control of cytokine products derived by biotechnological processes. Committee for Proprietary Medicinal Products: Ad hoc Working Party on Biotechnology/Pharmacy and Working Party on Safety Medicines. PMID- 1888492 TI - Note for guidance. Production and quality control of human monoclonal antibodies. Committee for Proprietary Medicinal Products: Ad hoc Working Party on Biotechnology/Pharmacy and Working Party on Safety Medicines. PMID- 1888493 TI - What is a biological? PMID- 1888494 TI - Control of biological products in the U.K. PMID- 1888495 TI - International symposium on pertussis evaluation and research on acellular pertussis vaccines. National Institute of Health in Tokyo and International Association of Biological Standardization. 14-15 September 1990 at Shizuoka, Japan. PMID- 1888496 TI - Increased sensitivity of antithymocyte globulin-treated newborn rat assay for metastasis. AB - Tumorigenic and metastatic abilities of FL, transformed human amnion, Vero and LLC-MK2, continuous monkey kidney cell lines (CCLs), none of which produced lung metastases in nude mice, were studied in ATG-treated newborn Wistar rats. Effects of subcutaneous (s.c.) and intraperitoneal (i.p.) inoculation of 10(6) and 10(7) cells were compared. l.p. inoculation of the same number of FL cells produced larger primary tumors, increased incidence of lung metastasis and more metastases per rat than s.c. inoculation. The same was true of the higher inocula administered by either route as compared to the smaller inocula. The CCLs (Vero at passages 320 and 323, LLC-MK2 at passage 306) inoculated either s.c. or i.p. induced small tumors regressing in all animals. After s.c. inoculation of 10(6) Vero or LLC-MK2 cells lung metastases did not develop in any rats, but 10(7) inoculum and i.p. administration of both size inocula caused single lung metastases. Thus, increased sensitivity of the rat system was achieved by larger size of the s.c. inoculum or the i.p. route of inoculation. Highly sensitive assay is especially important for evaluation of possible metastatic abilities of CCLs. PMID- 1888497 TI - Improvement of a Vero cell assay to determine diphtheria antitoxin content in sera. AB - Diphtheria antitoxin content in sera were determined automatically in Vero cell assay by spectrophotometric determination of the equivalence point between toxin and antitoxin followed by computer analysis of absorption values. The method was more accurate than visual reading and made handling of many samples easy. PMID- 1888498 TI - The immunogenicity of recombinant LC16mO vaccinia virus harboring HBsAg gene in mice. AB - It was found that hepatitis B surface antigen (HBsAg) expressed by recombinant vaccinia virus (RVV), rProHBmO143, harboring HBsAg gene was immunologically similar to plasma-derived HBsAg and immunogenicity of the rProHBmO143 was possible to evaluate by the skin scarification (SS) method using BALB/c mice. When we compared the immunogenicity of 10(8) TCID50 of the rProHBmO143 by the SS method with that of 0.125 ml of the plasma-derived hepatitis B vaccine (HB vaccine) given by intraperitoneal inoculation, the anti-HBs antibody eliciting ability of its RVV was almost the same as that of the HB vaccine with maintenance of high antibody titers, and the antibody responses rose further by re inoculation in association with HB vaccine, especially by using its RVV as a priming. Also, no virus was recovered from the liver, spleen or brain of the mice inoculated with rProHBmO143 by the SS method. Furthermore, in mice inoculated with rProHBmO143 and then inoculated with RVV harboring Japanese encephalitis virus (JEV) gene 24-weeks later, no effect was recognized on duration of anti-HBs antibody persistence while anti-JEV antibody is being produced. These results suggest that the rProHBmO143 is likely to become a practical live vaccine; a different immunization schedule to protect against hepatitis B virus and two or more kinds of RVV vaccines may be usable for the same animal or humans at intervals of some years. PMID- 1888499 TI - Quality control testing of surfaces for mammalian cell culture using cells propagated in a protein-free medium. AB - Mouse NCTC clone 929 L (L-929) cells were propagated continuously for 3 years as monolayers in a protein-free chemically-defined medium. These cells, designated L 929-WS, were used for quality control testing of the surfaces of commercially available cell culture plastic flasks. Differences in attachment and saturation density of L-929-WS cells in a protein-free culture medium were taken to define various levels of quality of the culture vessels tested. The rate of attachment and growth of L-929-WS cells on a surface of a given quality correlated directly with that of human embryonal fibroblasts and embryonal epithelial cells grown in a serum-free medium supplemented with growth factors and hormones. L-929-WS cells propagated continuously in a protein-free medium provide a simple and sensitive assay system for more general quality control testing of surfaces used for the culture of monolayer cells. PMID- 1888500 TI - The quantitation of rabies-specific antibodies. I. Modified counter immunoelectrophoresis. A rapid and sensitive method. AB - Modified counter immunoelectrophoresis was standardized with respect to dilution of tissue culture antigen and indicator serum, the incubation time for neutralization and the effect of an electric current. The technique was found to be sensitive enough to detect a minimum level of antibodies (0.5 IU/ml) by using a 16 mA current per slide for 2 h, indicator serum of 15 IU/ml and the use of an antigen at a concentration of 1:35. Above all, the incubation period did not affect the neutralization of the virus. The test was also applied to the detection of rabies-specific antibody levels in 73 human sera. The test was found to be simple, quick and economical for titration of rabies antibodies. PMID- 1888501 TI - The quantitation of rabies-specific antibodies. II. Factors affecting the sensitivity of the haemagglutination inhibition test. AB - Various factors affecting the HAI test for the quantitation of rabies-specific antibodies have been evaluated with a view to obtaining maximum sensitivity and reproducibility in tests using tissue culture antigens prepared in vero cells and concentrated by dialysis. Goose erythrocytes treated with proteolytic enzyme bromelian at a concentration of 0.025% were much more susceptible to HA than those that were untreated or erythrocytes treated with neuraminidase. In addition, other parameters like the use of a phosphate buffered saline (PBS) as a diluent at pH 6.2, incubation at 0-4 degrees C for 1.5-3 h were found to be most critical for achieving maximum HA activity. To remove non-specific inhibitors, serum samples were treated with aerosil, acetone in combination or alone. Of the 73 serum samples tested, removal of non-specific inhibitors by aerosil alone occurred in up to 54.79% of the samples, whereas using acetone-aerosil treatment followed by adsorption with goose erythrocytes, the inhibitors were removed in 98.67% of the samples to a level that was undetectable at the 1:4 starting dilution in the HAI test. PMID- 1888502 TI - The influence of ventilating tubes on the surgical treatment of atelectatic ears. AB - Forty children and 53 adults having 111 atelectatic ears were operated on and followed up. All patients underwent a tympanoplasty operation, while 27 patients underwent concomitant various mastoid operations. A ventilating tube was inserted in 55 out of the 111 atelectatic ears, while in 56 ears the tympanoplasty was left without a ventilating tube. After an average of 53.1 months of post operative follow-up we found that all ears were adequately aerated as long as a ventilating tube was in place. However, at the final check, once all ventilating tubes extruded, it was found that insertion of a ventilating tube at operation did not change the natural evolution of the atelectatic condition after surgery. Our conclusion is that the only way to overcome the atelectatic prone condition is to reinsert a ventilating tube whenever atelectasis reformation occurs. PMID- 1888503 TI - The influence of middle ear pressure on the lateral vestibulospinal tract neurons in cats. AB - The influence of changes in middle ear pressure on the lateral vestibulospinal tract (LVST) neurons was investigated in anesthetized cats. The activities of some LVST neurons increased with negative pressure and decreased with positive pressure. This tendency was stronger when pressure changes were applied to the contralateral middle ear than to the ipsilateral side. The influence of changes in middle ear pressure on LVST neurons was opposite to that on the vestibular nerve, suggesting the existence of inhibitory inter- and commissural neurons. PMID- 1888504 TI - Localization of the sensory neurons in the canine nodose ganglion sending fibers into the internal branch of the superior laryngeal nerve. AB - The distinct localization of the sensory neurons in the canine nodose ganglion that send fibers into the internal branch of the superior laryngeal nerve (the main sensory pathway from the larynx) was studied using horseradish peroxidase technique. The labeled cells were located mainly in the rostral one-third of the lateral side of the nodose ganglion. We conclude that the localization of these labeled cells does not reflect a difference in cellular role or function but is due to the course of the nerve's fibers. PMID- 1888505 TI - Papillary carcinoma in thyroglossal duct remnants. AB - About 100 cases of carcinoma arising in thyroglossal remnants have been reported in the world literature. Five additional cases were discovered incidentally on histopathological examinations of specimens following Sistrunk's operation for removal of thyroglossal cysts and are now reported. The possibility of preoperative clinical diagnosis and the modalities of treatment are discussed. PMID- 1888507 TI - Induced atelectasis of the middle ear and its clinical behavior. AB - Atelectatic ears are often treated with ventilating tubes for long periods of time. However, a certain percentage of atelectatic ears and retraction pockets resolve spontaneously over time. In order to determine whether self-aeration had been achieved in atelectatic ears previously fitted with ventilating tubes, the tubes were sealed and the ears were then closely followed. Out of 37 such tests, atelectasis did not recur in 4 ears, allowing their ventilating tubes to be removed. In 33 tests atelectasis redeveloped within 1-2h after the ventilating tube was sealed, with ears reverting to the same degree and shape as the original atelectatic condition. The seals were then removed, resulting in resolution of atelectasis. These observations were enforced by previous observations of similar changes and suggest that the partial pressures of the blood gases may be an important factor in controlling the level and possibly also the pathogenesis of atelectasis. The method of testing described also can be used in selected cases to determine whether or not a given atelectatic ear still requires a ventilating tube. PMID- 1888506 TI - Short nasal respiratory cilia and impaired mucociliary function. AB - A 48-year-old man was examined because of anosmia. He was otherwise healthy except for mild arterial hypertension. He had stopped smoking 20 years ago. Previously he had been exposed to sulfuric acid gases for 3 years in his work. Clinical examination revealed no findings to explain his anosmia. The patient was fertile, indicating normal sperm/cilia motility. Nasal mucociliary function was examined by radioactive tracer and found to be markedly and constantly impaired. Ciliary ultrastructure in cross-sections was normal. However, in longitudinal sections the length of the cilia varied from 0.6 microns to 3.9 microns. The mean length of the cilia from the cell membrane to the tip was 2.5 +/- 0.9 microns, in contrast to normal ciliary length of 5-7 microns. These findings represent a new structural defect among the various known ciliary abnormalities. PMID- 1888508 TI - Progressive hearing loss after single exposure to acute acoustic trauma. AB - Progressive hearing loss after single episodes of acute acoustic trauma (Knalltrauma) has been reported in only a few cases. Many authors dispute such a progressive evolution. Since this question is of obvious importance in cases evolving into lawsuits, its occurrence also arouses scientific interest. The present study reports 58 bilateral and 17 unilateral cases of acute acoustic trauma showing progression of more than 20 dB at least at one frequency. The mean follow-up time was more than 20 years. The incidence was estimated as less than 1% of cases involving acute acoustic trauma. The evolution of the progressive hearing loss did not show a specific pattern; in the unilateral group, there were no statistically significant differences between the progression in both ears. The findings clearly indicate that late progression of hearing loss due to single episodes of acute acoustic trauma does not exist unless the affected ear is exposed to additional damage not related to the initial trauma. PMID- 1888509 TI - Comparison of compound action potential audiograms with distortion product otoacoustic emissions in experimentally induced hydrops. AB - Endolymphatic hydrops was induced in a series of adult pigmented guinea pigs. Distortion product oto-acoustic emissions in general reflected the typical form of the hydropic compound action potential (CAP) audiogram, either with predominant low-frequency losses or a relatively flat audiogram. However, at certain two-tone combinations in some control ears the emissions could be smaller than expected from respective CAP audiograms, while in some hydropic ears the emissions could be larger than expected. The data presented here suggest that whilst the diagnostic value of distortion product emissions in the clinical situation might, at this time, be limited, the data from these emissions can give some insight into tonotopic hair cell function. PMID- 1888510 TI - Cerebral abscess complicating dilatation of a corrosive esophageal stricture. AB - A case is presented in which a metastatic cerebral abscess developed in a 62-year old female who required repeated dilatation for an esophageal stricture following accidental ingestion of liquid caustic soda. The literature is reviewed and management suggested for the avoidance of this uncommon complication. PMID- 1888511 TI - Structure and expression of the nerve growth factor gene in Xenopus oocytes and embryos. AB - A large part of the coding portion of the Xenopus nerve growth factor (NGF) gene has been identified and cloned by the use of a chicken cDNA probe and its sequence has been determined. Comparison of the derived amino acid sequence of mature Xenopus NGF with that of other species showed a high conservation, whereas comparison of the prepropeptide showed large divergent regions alternated with short conserved regions. Expression of the NGF gene was examined during development of oocytes and embryos. Surprisingly, NGF mRNA was found in the oocyte; it is present in small previtellogenic as well as in fully grown oocytes. NGF mRNA, passed to the embryo at fertilization, is degraded before the gastrula stage and starts accumulating again around the stage of the neurula. The association of NGF mRNA with polysomes is indicative of NGF synthesis during oogenesis. In fact, by using antibodies against mouse NGF it was possible to reveal NGF molecules present as precursors. These molecules accumulate during oogenesis and are maintained in the embryos up to the blastula stage; a very faint band corresponding to a smaller size peptide is sometimes detected. A maternal role for the NGF can be proposed, although a possible activity of NGF in the oocyte cannot be ruled out. PMID- 1888512 TI - Developmental regulation of a serum response element binding activity in amphibian embryos. AB - As part of our studies of transcriptional control during early development in vertebrates, we have examined embryos of the amphibian Xenopus laevis for the presence of sequence-specific DNA-binding proteins, using gel electrophoresis mobility-shift assays. Our analysis has focused on sequence elements in the cytoskeletal actin gene, whose embryonic transcription is initially activated at the gastrula stage, approximately 16 hours after fertilization. We detect activities capable of specific binding to two known transcriptional regulatory elements, the serum response element and the GC-box, located in the 5'-flanking region of the cytoskeletal actin gene. Binding activity specific for a region downstream of the transcriptional startsite is also detected, in a region which may be involved in controlling developmental activation of this gene. Serum response element-binding activity, as well as the downstream binding activity, is enriched in extracts from gastrula and neurula stage embryos, compared to egg extracts, suggesting that increased levels of one or both of these activities might play a role in developmentally timed transcriptional activation of the cytoskeletal actin gene in the embryo. PMID- 1888513 TI - Rabbit blastocysts accumulate [3H]quinuclidinyl benzilate in vitro. AB - Day-6 rabbit blastocysts were able to accumulate [3H]quinuclidinyl benzilate (QNB) from their environment. This accumulation was reduced approximately 50% in the presence of 1.5 x 10(-4) M atropine (an accepted antagonist for ligands which bind to muscarinic cholinergic receptors). The accumulation of QNB was sensitive to temperature and was apparently saturable. In the presence of 2 nM QNB, Day-6 blastocysts accumulated 30.3 +/- 2.0 fmoles per blastocyst. When the cellular elements alone were examined, lesser amounts of specific binding were detected. Owing to the complexity of this multicompartmental system, Scatchard analysis did not provide meaningful results. This accumulation appears higher than that reported for other tissues such as rabbit heart homogenates or rabbit uterine endometrial cells. This muscarinic cholinergic accumulation may have some roll in blastocyst-maternal recognition. PMID- 1888514 TI - Effect of RU486 on development and implantation of rat embryos. AB - This study evaluated the effects of postcoital treatment with the antiprogestin RU486 on transport, development and implantation of rat embryos. Doses of 0.1, 0.5, 1.0, 2.0, or 3.0 mg/rat of RU486 were injected subcutaneously on days 1, 1 + 2, or 4 of pregnancy. Autopsies were carried out on days 5 or 12 of pregnancy. RU486 provoked a significant dose-related reduction in the number of recovered embryos and inhibited their development (day 5) and decreased the number and size of implanted embryos (day 12). Treatment on day 4 was the least effective. Blastocysts recovered from RU486-treated rats exhibited comparable rate of trophoblastic outgrowth in vitro as the controls. Blastocysts transferred from RU486-treated rats to synchronous untreated pseudopregnant recipients yielded implanted embryos 12 days later in all recipients, although at a significantly lower rate than the controls. Blastocysts transferred from control pregnant rats to RU486-treated pseudopregnant recipients failed to implant completely when the dose was greater than or equal to 1.0 mg. The interceptive mechanism of postcoital treatment with RU486 in the rat involves loss of embryos from the reproductive tract and altered development prior to implantation. Endometrial receptivity or the ability of the uterus to retain the embryos until the time of implantation are also impaired by RU486. The embryos that survive these effects may experience delayed implantation in their mothers. PMID- 1888515 TI - Alterations in distribution of surface and intracellular antigens during epididymal maturation of rat spermatozoa. AB - The surface membrane of mammalian spermatozoa is known to undergo considerable conformational and organizational changes during epididymal maturation. However, much less is known about remodelling of intracellular membranes. In this communication we have used specific immunological markers to study the behavior of several antigens both on and within rat spermatozoa as they mature in the epididymis. Four monoclonal antibodies (McAbs) designated 5B1, 1B5, 2D6, and 1B6 were used to probe testicular and caput and cauda epididymal spermatozoa by indirect immunofluorescence and immunogold labeling techniques. None of the McAbs bound to testicular spermatozoa; in all cases, they became reactive only on spermatozoa which had reached the caput epididymis. McAb 5B1 was restricted to the outer acrosomal membrane (OAM) of the acrosomal cap domain. The epitope first appeared on antigen(s) with molecular mass (Mr) of approximately 200 kDa in immature spermatozoa, but later in mature spermatozoa the antigen(s) had Mr of approximately 160 kDa. The antigen(s) recognized by 1B5 McAb on the other hand was initially distributed over the OAM of the entire acrosomal domain (cap + equatorial segment), but during maturation it became progressively more restricted in area until in cauda spermatozoa only the anterior tip of the OAM bound the McAb. McAb 2D6 also bound to the entire OAM and acrosomal contents of caput spermatozoa, but, unlike 5B1 and 1B5 McAbs, reactivity was transient. That is, staining was first detected in caput spermatozoa but then disappeared in corpus and cauda spermatozoa. In contrast to all of the above, 1B6 McAb bound to the surface membrane overlying the entire head domain of caput spermatozoa, but during maturation it became restricted to the postacrosomal domain. These results indicate that, in addition to remodeling of the surface membrane during epididymal maturation, extensive processing of intracellular membrane antigens also takes place and that it is very active within the acrosome. The nature of these intracellular processing events remains to be elucidated, but they may have important consequences for membrane fusion and cell recognition phenomena during fertilization. PMID- 1888516 TI - Vitrification of mouse oocytes: improved rates of survival, fertilization, and development to blastocysts. AB - Rall and Fahy's (1985) vitrification procedure for the cryopreservation of 8-cell embryos was applied to unfertilized mouse oocytes. Unchanged, this method resulted in a mean of 24.1% of vitrified oocytes fertilizing and developing to blastocysts in vitro. Exposure of oocytes to the cryoprotectant media, but without the vitrification, resulted in 30.8% developing to blastocysts. Modifications to the durations of and media used in the dilution and equilibration steps of the procedure produced a final protocol giving a mean of 55.4% of vitrified oocytes and 72.4% of nonvitrified VS1-exposed oocytes developing to blastocysts; 85.7% of control oocytes develop to blastocysts. Osmotically induced damage was found to be the most important cause of loss of viability in these methods. Cooling of oocytes to 5-8 degrees C during the procedure had no significant effect on their viability. No parthenogenetic activation of oocytes occurred as a result of exposure to the procedure. PMID- 1888517 TI - Effect of 6-dimethylaminopurine on germinal vesicle breakdown of bovine oocytes. AB - The effect of 6-dimethylaminopurine (6-DMAP) on germinal vesicle breakdown (GVBD) and maturation in bovine oocytes was investigated in this study. This puromycin analog has been shown to be an inhibitor of phosphorylation. Whereas GVBD occurred in nearly all oocytes (96.8%, 120/124) in control medium, presence of 6 DMAP (2 mM) blocked this process almost completely, irrespective of the presence (98.3% GV, 349/355) or absence (97.1% GV, 165/170) of cumulus cells. When lower concentrations of 6-DMAP were used (100-500 microM), GVBD was observed in 87.9% of oocytes, but their maturation was arrested at late diakinesis-metaphase I stage. The inhibition of GVBD was fully reversible, but most of the metaphase II plates were abnormal (80%). To assess whether the action of 6-DMAP is different from the inhibitors of protein synthesis, metaphase II oocytes were exposed to either cycloheximide or 6-DMAP, respectively. Whereas in cycloheximide supplemented medium approximately 80% of the oocytes were activated, parthenogenetic activation was much less frequent after incubation in 6-DMAP (14.5%). Fusion studies showed that, even if GVBD occurs in 6-DMAP supplemented medium, the level of the maturation-promoting factor (MPF) is decreased. These experiments may indicate the importance of phosphorylation for GVBD in cattle oocytes. PMID- 1888518 TI - Oviduct function in pigs, with particular reference to the pathological condition of polyspermy. AB - Because the exceptionally high incidence of polyspermic fertilisation has been emphasised as a major defect in systems of in vitro fertilisation in pigs, the aetiology of the condition has been analysed in a series of experiments in vivo in the search for a common underlying cause and possible means of mitigation. Whereas the defense mechanism against polyspermy in pig oocytes is classically viewed as zona reaction, more recent evidence suggests a secondary block at the vitelline surface. Both blocks may be compromised in situations leading to polyspermy, although deleterious influences seem to be expressed principally in an inadequate zona block, as judged by the presence of perivitelline spermatozoa. Postovulatory aging of mammalian oocytes prior to sperm penetration leads to polyspermy, as can be demonstrated in pig eggs. The primary lesion may concern the cortical reaction, owing to a delayed and incomplete exocytosis of the vesicular contents. Eggs ovulated after gonadotrophin treatment during the luteal phase of the cycle show a high incidence of polyspermic penetration (60.6%), as do those shed at estrus in animals treated with progesterone systemically (40%) or by local microinjections in the oviduct wall (32.3%). Whereas progesterone may be modifying interactions of the gametes and responses of the egg organelles in all four above experimental situations, enhanced numbers of spermatozoa ascending a more patent isthmus appear to be the principal cause of polyspermy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1888519 TI - [Hemodynamic effects of captopril in acute infarct of the anterior myocardium]. AB - OBJECTIVE: Evaluation of haemodynamic effects after sublingual administration of 25 mg of captopril in patients with Acute Anterior Myocardial Infarction within the first 48 hours. DESIGN: Determination of basal parameters and 30 minutes after 25 mg of captopril. SETTING: Patients admitted in the ICU with Anterior Myocardial Infarction diagnosis. PATIENTS: 41 consecutive patients; 22 patients submitted to thrombolysis with streptokinase; 19 patients submitted to conventional therapy. RESULTS: A) In the whole group: No significant change in the HR, PAP, CI, SI, MAP, SVR, PR. RA and CWP were reduced. B) In thrombolysed patients: No significant change in HR, RA, PAP, CWP, MAP, SVR, PR. CI and SI were significantly increased. C) In non-thrombolysed patients: No significant change in HR, PAP, CI, SI, SVR, PR. RA, CWP and MAP were reduced. CONCLUSION: 1. We found no significant hypotension with sublingual captopril in Acute Myocardial Infarction. 2. Non-thrombolysed patients showed a greater reduction of arterial pressure. 3. Thrombolysed patients had significant increases in systolic function indices. PMID- 1888520 TI - [Echo-Doppler in patients undergoing mitral commissurotomy. Comparison of open and closed commissurotomy]. AB - OBJECTIVE: 1. To evaluate with Echo-Doppler the medium/long term results of mitral commissurotomy. 2. To compare the results of open mitral commissurotomy to those of closed commissurotomy. PATIENTS AND METHODS: The Echo 2D-Doppler study has been performed in 117 patients (104 females and 13 males), randomly selected among patients previously submitted to open (62 d.) or closed (55 d.) mitral commissurotomy, with greater than or equal to 12 months follow-up. Pulsed and continuous Doppler recordings were obtained in all 117 patients, and the following parameters were evaluated: Maximum Mitral Gradient (MG); mitral valvular area calculated by half-pressure time (MVA); presence of mitral regurgitation greater than or equal to grade 2 (MR); evaluation of systolic Pulmonary Artery pressure (PAP) by the gradient RV/RA + 14mmHg, in the patients with tricuspid insufficiency; acceleration time (ACT), ejection time (EJT) and the relation ACT/EJT in pulmonary artery. To compare the results of open commissurotomy, to those of closed commissurotomy, and in order to minimize the pre-operative differences between the patients submitted to each of these interventions, only the patients in the same NYHA functional class before surgery (class III), and in sinus rhythm have been selected. In this way two groups were compared: group A-24 patients with open commissurotomy and group F-37 patients with closed commissurotomy. RESULTS: in the total of patients the results were: MG-9.8 +/- 4.2 mmHg; MVA-2.3 +/- 0.95 cm2; MR 16 pts. (13.7%); PAP obtained in 30 pts. (25.6%) -27.47 +/- 1.18 mmHg; the ACT, the EJT and the relation ACT/EJT in PA were respectively 115.63 +/- 34 ms, 309.9 +/- 38.5 ms, 0.37 +/- 0.1. The Doppler parameters obtained respectively in group A and in group F were: MG 8.96 +/- 4.5 mmHg and 10.38 +/- 3.82 mmHg (ns); MVA 2.62 +/- 1.01 cm2 and 2.08 +/- 0.84 cm2 (ns); MR 8.3% and 15.6% (ns) (Fig.3); the PAP have been calculated on 5(20.8%) patients in group A and on 10(27%) patients in group F and their respective values were 30.78 +/- 0.48 mmHg and 28.26 +/- 1.11 mmHg (ns); ACT 109.09 +/- 41.55 ms and 116.67 +/- 33.22 ms (ns); EJT 297.27 +/- 72.94 ms and 308.7 +/- 41.58 ms; ACT/EJT 0.35 +/- 0.12 and 0.38 +/- 0.10 (ns). CONCLUSION: Both open and closed commissurotomy revealed to be good therapeutic alternatives to mitral stenosis with identical long term results as evaluated by Echo-Doppler. The results of percutaneous mitral valvuloplasty should be compared with these in the future. PMID- 1888521 TI - [Residual myocardial function in dilated myocardiopathy. Response to post extrasystolic potentiation]. AB - OBJECTIVE: to evaluate the effectiveness of post-extrasystolic potentiation (PESP) to detect latent residual contraction function in patients (pts) with idiopathic dilated cardiomyopathy. DESIGN: retrospective study in pts referred for cardiac catheterization. SETTING: Haemodynamic Laboratory of Cardiology Service, Bellvitge Hospital. Barcelona, Spain. PATIENTS: the criteria for including pts with sinus rhythm were (SR): 1-The appearance of an extra beat R' on the ventriculogram; 2-The location of R' in relation to the preceding sinus beat R1 and the following beat R2 being such that R1-R' less than R'-R2. In patients with atrial fibrillation (AF), the criteria were: 1-An early beat Re had to be identified; 2-R1-Re interval had to be at most half of the Re-R2 interval; 3-The length of the cardiac cycle preceding R, has to be equal to the mean cycle length. All the patients with an increase of the ejection fraction (EF) from R, to R2 less than 12% were included in group A: 12 patients (3 females, 9 males, mean age 51 years, 5 SR, FE 27 +/- 10%). In group B were included patients with an increase of the ejection fraction greater than or equal to 12%; 14 patients (4 females, 10 males, mean age 50 years, 7 SR, FE = 31 +/- 7%). MEASUREMENTS: In each ventriculogram we assessed the performance of left ventricle on R1 and R2 beats by determining: 1-Left ventricular end diastolic (EDV), end systolic (ESV), stroke (SV) volumes; 2-Volumes index (EDVI), (ESVI) (SVI); 3 - Ejection fraction (EF) - Change in ventricular contractility from R1 to R2, delta EF. RESULTS: in the sinus rhythm group the values of R1 and R2 were respectively: EDV: (184 +/- 48 ml/m2; 191 +/- 17 ml/m2; NS); SVI (53 +/- 19 ml/m2; 80 +/- 22 ml/m2; p less than 0.01) FE (29 +/- 7%; 42 +/- 10%; p less than 0.01), delta EF 13 +/- 6%. The change of the ejection fraction from R1 to R2 in pts with SR and AF were respectively: 13 +/- 6% and 11.5 +/- 6.4%; NS. Group A: Deterioration of the functional class and two deaths occurred. Group B: Improvement in functional class in all cases but one. CONCLUSION: our data suggest that augmented ventricular filling and consequent Starling's effect is not a significant contribute for PESP in pts with dilated cardiomyopathy. The analysis of post extrasystolic beat in SR pts and the beat following an early beat with a long diastole in AF, is a valuable method of determining the residual left ventricular function in this group of pts. PMID- 1888522 TI - [Ebstein's anomaly. Clinical aspects and surgical therapy]. AB - OBJECTIVE: We reviewed the clinical findings and surgical results of Ebstein's anomaly in adult and adolescent age. DESIGN: Retrospective analysis on clinical data, surgery and follow up. SETTING: Patients (pts) studied in the Cardiology and Cardiothoracic Surgery Departments of the Santa Marta Hospital, Lisbon. PATIENTS: All pts in whom Ebstein's anomaly was diagnosed by cardiac catheterization or echocardiography or both, between 1875 and 1989 were included. RESULTS: There were 8 cases (4 female and 4 male). The age varied from 15 and 53 years. Cyanosis and dyspnoea were the presenting features in 7 pts. One of the youngest pts had asymptomatic murmurs. Late appearance of cyanosis had no relation with prognosis. Three pts had pulmonary tuberculosis. One woman had no deterioration in cardiac function during two pregnancies. Clinical findings were variable and ranged from absent murmur with third and fourth sounds to systolic murmurs of high intensity. The ECG was abnormal in all pts. A case with delta wave and normal PQ interval was noted. On the chest X-ray we found cardiomegaly in all pts. Echocardiograms were recorded in 6 pts. The delay of tricuspid valve closure on mitral closure was not always diagnostic. Uncomplicated catheter studies were done in 6 pts. Two pts had associated cardiac lesions: ventricular septal defect (VSD) with pulmonary hypertension and mild pulmonary valve stenosis. Right ventricular angiographies were diagnostic in all cases. During medical follow up from 1 year to 10 years (mean-4) one death occurred in one pt with VSD. In the remaining 4 cases no deterioration in cardiac function or cyanosis was noted. Three pts were operated. The indications for surgery were: severe heart failure and/or increasing cyanosis. Two pts had tricuspid valve replacement with biological prosthesis. One pts had Danielson's tricuspid annuloplasty. During surgical follow up from 2 to 15 years (mean-7) functional class improved and cyanosis disappeared in 2 pts and it decreased in the other. CONCLUSION: In our series of pts with Ebstein's anomaly clinical findings were variable. The indications for surgery were heart failure and cyanosis. The 3 pts operated are alive and have mild symptoms. PMID- 1888523 TI - Incidence, characteristics and coronariographic significance of myocardial ischemia during daily life in patients with angina pectoris. AB - OBJECTIVES: To evaluate the incidence, characteristics and angiographic significance of myocardial ischemia detected on Holter monitoring in a group of patients with stable angina pectoris. SETTING: Department of Cardiology of a Central Terciary Hospital. METHODS: In 24 patients (pts) with stable angina pectoris and proven coronary artery disease (11 pts with left main or three vessel disease; 13 pts with one or two vessel disease), a 24 hour Holter monitoring was performed. Two groups of ischemic episodes were considered: Group I with 65 ischemic episodes detected in pts with left main or three vessel disease and group II constituted by 17 ischemic episodes detected in pts with one or two vessel disease. RESULTS: The incidence of myocardial ischemia was 91% in pts with left main or three vessel disease and 46% in pts with one or two vessel disease. Statistically significant differences were seen between group I and II concerning the mean heart rate variation from two minutes before onset of ST segment depression to its onset (3.5 bpm vs 7.4 bpm; p less than 0.05) and from the onset of ST-segment depression to its maximal depression (6.5 bpm vs 15 bpm; p less than 0.000001). CONCLUSIONS: The presence of myocardial ischemia and some of its characteristics on Holter monitoring seem to have a relation with the severity of coronary artery disease in patients with stable angina pectoris. PMID- 1888524 TI - [Pulmonary embolism. A propos of a case treated with APSAC]. AB - One describes the clinical case of a patient suffering from massive pulmonary embolism under a state of shock who was successfully treated with APSAC 30 units in one single bolus. Thrombolytic agents provoke a rapid destruction of thrombi which lead to a very important and fast hemodynamic improvement. These agents have a great improving action, compared to heparin, in the alterations of pulmonary diffusion provoked by embolism. Most of the times, they also avoid surgery and the appearance of cor pulmonale. APSAC seems to be effective and secure. PMID- 1888525 TI - [Angiotensin I converting enzyme inhibitors in ischemic cardiopathy]. PMID- 1888526 TI - [Cytogenetic adaptive response induced by low dose radiation]. AB - Human and rabbit peripheral blood lymphocytes were irradiated in vitro with 1.5 Gy x-rays after exposure to 0.01 Gy of x-rays (dose rate: 0.01 Gy/min). The frequency of chromosome aberration in the cells pre-exposed to 0.01 Gy of x-rays at Go, G1, S and G2 phases of cell cycle respectively was markedly lower than that in the cells irradiated with 1.5 Gy alone (P less than 0.01). This adaptive response would last for 3 cell-cycles, beyond which the damage of the chromosome following the second large dose occurred with the same magnitude as that without a previous conditioning exposure. However, when the low dose was repeated after the third cell cycle the adaptive response could be revived. Meanwhile, it was found that the adaptive response could be also induced in vivo in the bone marrow cells and germ cells of mice by low dose irradiation. In addition, the effect of dose rate of the first irradiation on the induced adaptive response was also studied. PMID- 1888527 TI - [High resolution chromosome G-banding pattern of domestic pig of China]. AB - Lising methotrexate or thymidine treatment to induce synchronous division, combined with GTG technique, the high resolution banded chromosomes of seven domestic pig breeds of China were investigated. No distinct difference was found among then. Hence, in line with The International System for Human Cytogenetic Nomenclature, a standard idiogram of high resolution G-banded karyotype of domestic pig is suggested in this paper. In the idiogrammatic presentation of G banding pattern, all the regions and bands of each pair of chromosomes are designated and described with slight modifications for the landmark system. Up to 444 bands were detected per haploid set, including the X and Y chromosomes, a number nearly two times as much as that in banded metaphase chromosomes. PMID- 1888528 TI - [The effects of upstream region of SUC2 gene on its expression]. AB - A series of deletions were made at upstream region of SUC2 gene with the direction from about -900 bp to the initiation codon. The DNA fragments, which contain SUC22 gene and its deleted upstream region, were inserted into multicopy plasmid. After transforming resulted plasmid into SUC strain, the invertase activities produced by the transformants were determined. Under glucose repressing condition, the glycosylated invertase produced by transformants with deletion from -636 bp to -179 bp of SUC2 gene were gradually increased. The transformants with deletion down to -223 bp and -179 bp could produce about 100 times higher glycosylated invertase activity as compared to wild type. Under glucose derepressing condition, the glycosylated invertase produced by transformants with deletion from -395 bp to -179 bp of SUC2 gene were only slightly more than that produced under glucose repressing condition. Under either glucose repressing or derepressing condition, the transformants with deletion at 89 bp and -41 bp produced only a little of glycosylated invertase, while they produced remarkably higher nonglycosylated invertase activity. PMID- 1888529 TI - [Study on immunoglobulin allotypes in the Chinese: a hypothesis of the origin of the Chinese nation]. AB - This paper reports the distribution of immunoglobulin Gm and Km allotypes in 74 Chinese geographic populations. These populations are derived from 24 nationalities comprising 96.6% of the total population of China. A total of 9,560 individuals were phenotyped for Gm (1,2,3,5,21) factors and 9,611 for Km(1). Phylogenetic trees were constructed on the basis of Gm haplotype frequencies and genetic distances. The results of clustering analysis show the heterogeneity of the Chinese nation, and confirm the hypothesis that the modern Chinese nation originated from two distinct populations. One population originating in the Yellow River valley, and the other originating, in the Yangtze River valley during the early part of neolithic times (to date 3,000--7,000). Frequencies of the Gm haplotype of 74 Chinese populations were compared with those from 33 populations from major racial groups. The results suggest that during human evolution, the Negroid group and Caucasoid-Mongoloid group diverged first, followed by a divergence between the Caucasoid and Mongoloid. Interrace divergences are high in comparison with interrace divergences. There appear to be two distinct subgroups of Mongoloid, Northern and Southern Mongoloid. The Northern and Southern Mongoloid have Gm1;21 and Gm1,3;5 haplotypes as race associated markers, respectively. Furthermore, the Caucasian associated haplotype Gm3;5 was found in several of the minorities living in the northwest part of China. The amount of Caucasian admixture has been estimated. The presence of the Gm3;5 haplotype is attributed to the Caucasians living in Central Asia throughout the "Silk Road." In contrast to the Gm haplotype distribution, Km1 gene frequencies showed a random distribution in the populations studied. PMID- 1888531 TI - [The application of alpha-globin-3'HVR probe for DNA fingerprinting in forensic science]. AB - Using alpha-globin-3'HVR as the molecular hybridization probe, A clear and readable DNA fingerprint has been obtained. Based on the DNA fingerprint analysis of 200 unrelated individuals living in Beijing area, the probability of chance association of two random individuals was 4.0 x 10(-12). The study of 32 related individuals of 6 families showed that the inheritance of DNA fingerprint bands conformed to the Mendelian law. The method is reliable for the individual identification and paternity test. It provides a scientific basis for solving cases such as rape, homicide etc. and it has been used in our actual case work. PMID- 1888532 TI - [Expression of human lymphotoxin gene in CHO-DHFR- cells]. AB - A recombinant plasmid p91-HuLT was constructed with a human lymphotoxin (HuLT) gene 2.4 kb EcoRI fragment and a mammalian cell expression vector plasmid p91023. The HuLT EcoRI DNA fragment covers entire coding sequence and some 3(1) non translated region sequence of the gene, p91-HuLT DNA was used to transfect Chinese hamster cell line CHO-DHFR- cells by using calcium phosphate-DNA coprecipitation method, and DHFR+ transfectants were obtained. RNA dot blot hybridization analysis showed that the HuLT mRNA was produced by p91-HuLT in transfectants. The results of MTT dye reduction assay indicated that the DHFR+ cell lines we obtained constitutively synthesize and secrete the HuLT with the cytotoxic activity of at least 200 units per mL of medium. PMID- 1888533 TI - [Study on the estimation methods of genetic parameters with mixed family]. AB - By theoretically supposing the male variance component be equal to the female variance component, a new method and an approximate estimation method of heritability are suggested on the basis of decomposing the expected mean squares in variance analysis with mixed families. Seven estimation methods of heritability are compared by an actual estimation example. The results indicate that the difference of the estimation value between full-sib analysis method and the method suggested in this paper is the smallest and the standard error of estimated heritability by the latter method is the smallest among the standard error of estimated heritability by the latter method is the smallest among the seven methods. Also the approximate method is effective. For all methods, the more disequilibrium of the data, the bigger difference of the estimate value by those methods. The new method can be used when the difference of variance components between male and female is relatively large with full-sib analysis in actual estimation. Moreover, the new method is easily calculated because the two way classification data was analyzed by one-way classification variance analysis and the average relationship coefficient among mixed families may not need to be calculated. PMID- 1888530 TI - [Investigation of C4 haplotypes in Han nationality of Hubei Province in China]. AB - C4 haplotypes of 93 unrelated families of Han nationality in Hubei Province were determined by means of a method established in our laboratory based on the techniques recommended in the 4th International Workshop for the Genetics of Complement and the method of Carboxypeptidase B developed by Zhang in Australia. 310 C4 haplotypes were analysed. The haplotype frequency of A3B1 (0.4194) was found to be the highest in Han nationality of Hubei in China. The others are as follows: A3B2: 0.1161, A2B1 and A4B2: both 0.0903, AQOB1: 0.0645, A3BQO: 0.0548, AQOBQO: 0.0322, A2B2: 0.0256, A4B1: 0.0161, A2B92: 0.0129. Some kinds of rare haplotypes were also discovered. Significant positive-linkage disequilibrium parameters (delta) were found in haplotypes of A4B2, AQOBQO and A2B92, while the significant negative delta was observed in that of A4B1 and AQOB2. Our data were compared with those of Japanese, Caucasian in USA and Germany, Negroids in South Africa are discussed in the paper. The differences among them. PMID- 1888535 TI - [Anatomy of post-ethmoid sinus and its near-by structures]. PMID- 1888534 TI - [Influence of beclomethasone dipropionate on rabbit's nasal mucosa, adrenal and frog oral mucociliary activities]. AB - The histology and surface ultrastructures of the nasal mucosa and adrenal after intranasal beclomethasone dipropionate (BDP) 400mg/day for 5 weeks were observed with light and scanning electron microscopes in rabbits. Besides, the ciliary activities in vitro and mucociliary transportation function in frog oral mucosa after administrating BDP were studied. The results showed that intranasal BDP did not produce significant lesions of the nasal mucosa and atrophy of the adrenal in rabbits and BDP did not reduce oral mucociliary activities in frog. It suggests that intranasal BDP therapy is safe. PMID- 1888536 TI - [Nasal breathing pressure and the flow test]. AB - The evolution of nasal breathing pressure and a flow test had been introduced. Five abnormal types of nasal function were analyzed. The test is very useful to rhinologists by offering an objective diagnostic information, it is also useful to physicians and other medical workers, because nasal activities is related to cardio-pulmonary-vascular function. PMID- 1888537 TI - [Differentiation between allergic rhinitis and vasomotor rhinitis. Light and electron microscopic studies]. AB - The pathological changes of nasal mucosa from allergic rhinitis and vasomotor rhinitis were observed. The results showed that the general characteristic was vascular dilatation with increased permeability and glandular proliferation with increased secretory activity. The pathological difference between mucous membranes of allergic and vasomotor rhinitis were mainly cellular infiltration and degree of damage on vascular wall. In allergic rhinitis there were more eosinophils, basophils, neutrophils and some mast cells and plasma cells in nasal mucosa. Gap formation in capillary wall was found in allergic nasal mucosa, there were less cellular infiltration and no gap formation in vasomotor rhinitis. PMID- 1888538 TI - [Regeneration of the severed facial nerve]. AB - Twenty-four specimens from distal end of the human facial nerve obtained at reinnervation surgery (nerve grafting) were studied by light and electron microscopies. In 21 specimens, with complete severance of the facial nerve but continuous neurilemma confirmed during surgery, regeneration phenomenon was observed. Histological examination of the auricular branches of vagus nerve (2 cases) and auriculotemporal nerve (1 case) with their communication portion showed regeneration of axons into the facial nerve below the level of sectioning. This phenomenon points to the possibility that surgically interrupted communication branches may provide new endoneural tubes following inevitable degeneration of communication branches. These tubes facilitate motor axons growing through nerve graft. PMID- 1888539 TI - [Relation between the DNA content in laryngeal cancer cell and its clinical behaviour]. AB - The DNA contents of 45 cases of laryngeal cancer have been analyzed by flow cytometry (FCM). The DNA index (DI) ranged from 0.9 to 3.39; proliferative index (PI) was 27.3%. Among them, 13 cases (28.8%) were diploid and 31 (68.8%) distinctly aneuploid. Correlation has been found between DI and the histopathologic grades of the tumors. The larger the DI, the higher the histopathologic grade (P less than 0.05). The mean value of the PI in supraglottic types was higher than that of glottic types. DNA content analysis also showed that diploid tumor had a better prognosis and longer survival than those with higher DI values. In addition, the proliferative activity of cancer cell was found to be markedly reduced after irradiation which demonstrates that preoperative radiotherapy is favourable for laryngeal cancer. PMID- 1888540 TI - [Value of laryngofissure and frozen biopsy in pathological diagnosis of laryngeal cancer]. AB - Thirty-two cases of laryngeal tumor were treated from January 1986 to December 1989. Thirty cases with laryngeal cancer were diagnosed by laryngo-fissure with frozen biopsy. Before laryngo-fissure, there were no positive pathological findings despite repeated examination and biopsy. The authors believe that laryngo-fissure with frozen biopsy is a reliable method for diagnosis of suspected laryngeal cancer. Otherwise, the diagnosis and treatment will be delayed. PMID- 1888541 TI - [Nasal polyps]. PMID- 1888542 TI - Full coverage cosmetic dentistry and gingival health. AB - Beautiful, healthy gingival tissue is achievable with full coverage restorations that are biologically compatible. The restorations must meet the following requirements: (1) respect for the marginal gingiva by proper preparation of the tooth and the use of a soft tissue model; (2) careful subgingival depth placement; (3) proper subgingival and supragingival contours of the temporary and final restorations; (4) healthy gingiva prior to placement of final restorations; (5) marginal integrity; and (6) polished bonding interface. PMID- 1888543 TI - Dentin bonding: overview of the substrate with respect to adhesive material. AB - The current challenge in adhesive dentistry is to develop dentin bonding systems that will reproducibly achieve high bond strengths similar to those obtained between resins and acid-etched enamel. Some of the limitations of dentin as a bonding substrate are that it changes its structure as it is prepared deeper, it is difficult to dry, and its smear layer is weak. Further, it is difficult to avoid contaminating proximal boxes with blood. Such contamination lowers dentin bond strengths to very low values. Decontamination of such dentin must be done prior to resin placement. The forces of polymerization contraction depend, in part, on the shape of cavities and how they are filled. Bulk filling of class I cavities can lead to conditions in which the forces of polymerization contraction exceed dentin bond strength with some materials and locations. The future development of resin systems that do not shrink on polymerization would eliminate many current problems in adhesive dentistry. PMID- 1888544 TI - Evaluation of effects of application of a citroxain-containing dentifrice. AB - The benefits to the patient of the removal of tooth deposits is well documented. Should such removal provide the additional effect of "whitening" the tooth surface, an additional cosmetic benefit would be provided. This study documents that a Citroxain-containing dentifrice provides all of these benefits. PMID- 1888545 TI - At-home bleaching system: effects on enamel and cementum. AB - An analysis by scanning electron microscopy was undertaken to investigate the effects of bleaching on enamel-cementum surface morphology. Teeth were investigated in five groups: control; vital bleached for 5, 15, and 30 days; and 37 percent phosphoric acid gel etched for 20 seconds. Only the gel-etched group exhibited etching patterns. Shade change in vital bleached teeth was noted in the group vital bleached for 30 days. PMID- 1888546 TI - Reshaping tooth contours with direct resins. PMID- 1888547 TI - Principles and mechanisms of bonding with dentin adhesive materials. AB - This article reviews six dentin bonding agents with regard to composition of the individual components of each of the systems. Adhesion mechanisms are discussed relative to the chemical compounds mediating the bond. Adjunctly, inspection of the bonding sites between the different adhesives and human dentin by scanning electron microscopy elucidates the bonds formed as far as detail reproduction as an indicator for wetting ability or mechanical interlocking. PMID- 1888548 TI - Role of biodental engineering factors (BEF) in the etiology of root caries. AB - A preliminary study and hypothesis of the etiology of root caries is presented with appropriate data suggesting that biodental engineering factors (BEF) be introduced into the equation that is generally accepted in the formation of all caries. Principally, because of the rapid progression and location of root caries, BEF in addition to bacterial plaque and suitable substrate contribute to the development of these unique lesions. The dominant and most significant factors recognized by bioengineers are tooth flexure, stress concentration, stress corrosion, and piezo-electricity. All of these factors interplay during the dynamics of occlusal activity causing the loss of tooth substance. A new and revised model is being presented that provides a basis for the etiology of root caries. PMID- 1888549 TI - Amalgam controversy--media hype or reality. PMID- 1888550 TI - Bond strength of composite resin to enamel bleached with carbamide peroxide. AB - Bleaching with 35 percent hydrogen peroxide causes enamel surface changes, which result in lower bond strengths of composite resin. Although a previous SEM study showed that home bleaching with 10 percent carbamide peroxide does not cause such surface changes, the results of our study indicate that carbamide peroxide bleaching reduces the shear bond strength of composite to etched enamel. Removal of surface enamel, however, restores bond strengths to normal levels. PMID- 1888551 TI - Adhesion to dentin. AB - The bond strengths of dentinal bonding systems to dentin and the microleakage at the dentinal bonding system to dentin interface are often determined in laboratory studies prior to the clinical evaluation of these systems. The shear bond strengths of some of the third generation dentinal bonding systems to dentin and the microleakage at the dentinal bonding system to dentin interface are discussed. In addition, the shear bond strengths of fluoride-containing liners/bases and the fluoride release from these systems are evaluated. PMID- 1888552 TI - Microleakage of dentin adhesive systems. AB - Five different dentin adhesives were evaluated under various experimental conditions (using different restorative materials, placement techniques, and specimen storage). A silver-staining technique was used to detect microleakage. Pentra Bond II was less effective than Tenure in prevention of marginal leakage, but similar to Scotchbond 2 and Gluma. PMID- 1888554 TI - Differential diagnosis of perennial rhinitis. PMID- 1888553 TI - Shear bond strength of Dicor using resin adhesive systems and light activated cement. AB - A laboratory study was conducted to determine the shear bond strength to dentin of etched and silane-treated Dicor castable ceramic glass using a resin cement and newer generation adhesive systems. Scanning electron microscopy (SEM) examinations were also completed to evaluate the failure sites. The mean shear bond strength of the control (resin cement only, no adhesive system) was 2.1 +/- 1.2 MPa. The shear bond strength values determined for the adhesive systems and resin cement are as follows: Prisma Universal Bond 2, 18.7 +/- 2.9; XR Primer/XR Bond, 16.9 +/- 6.4; Scotchbond 2, 15.8 +/- 6.2; Tenure Solution, 15.4 +/- 4.5; and Gluma, 14.8 +/- 5.5 MPa. SEM examinations of the debonded specimens attached with Prisma Universal Bond 2 and Tenure Solution showed a complex failure pattern with cohesive failure in the glass ceramic material and adhesive failure between the resin cement and the etched and silane-treated glass surface. The debonding pattern of specimens attached with XR Primer/XR Bond, Scotchbond 2 and Gluma were primarily adhesive between the dentin and resin materials. The results of this study support the use of an adhesive system in conjunction with a resin cement for placement of Dicor castable ceramic restorations. PMID- 1888555 TI - Nasal polyps. State of the art. PMID- 1888556 TI - Clinical and physiological effects of fluticasone propionate aqueous nasal spray in the treatment of perennial rhinitis. PMID- 1888557 TI - The inflammatory basis of rhinitis. PMID- 1888558 TI - Childhood obsessive-compulsive disorder. AB - Childhood OCD is a distressing and debilitating condition. Childhood OCD is not a simple exaggeration of the rituals and superstitions that occur over the course of normal development. More males than females are diagnosed as having OCD. Not unexpectedly, anxiety and affective disorders are often associated with childhood OCD. Compulsive personality disorder is also an associated feature for a proportion of children with OCD. Treatment usually involves individual psychotherapy and family counselling, although behavioural treatment and medication (clomipramine) have also been used by clinicians. PMID- 1888559 TI - Conductive education. PMID- 1888560 TI - Screening for congenital dislocation of the hip in Australia. PMID- 1888561 TI - Possible mechanisms responsible for the sudden infant death syndrome. PMID- 1888562 TI - Two decades of change: cot deaths and birth score items in Canterbury, New Zealand. AB - The individual items of two birth scores and the scores themselves were examined for a sample of 2065 mothers and infants pairs for any changes between 1968 and 1986. About 100 births were randomly sampled for each year. The scoring systems used were the Sheffield risk score and the Christchurch-Invercargill-Dunedin score. A total of eight items from these scores was examined. The purpose was to discover whether the increasing cot death rate in Canterbury could be attributed to an increasing proportion of vulnerable infants, as determined by the items in the risk scores. No such relationship was uniformly found. PMID- 1888563 TI - Aluminium absorption in infancy. AB - The use of aluminium-containing medications and aluminium contamination of infant formulae is common. We aimed to determine whether aluminium absorption occurs after antacid ingestion. Plasma and urinary levels of aluminium were measured before and after antacid therapy in seven infants whose mean gestational age was 36 +/- 2 weeks and postnatal age 11 +/- 5 days. Antacid therapy (400-800 mumol aluminium) was given with feeds for 2 days. Plasma aluminium levels increased and reached toxic levels (0.64 +/- 0.33 mumol/L vs 3.48 +/- 2.86 mumol/L, P = 0.029). Urinary aluminium: creatinine ratio also increased. These results demonstrate that infants absorb aluminium from antacids and raise the concern of aluminium toxicity. PMID- 1888564 TI - Duration of hospitalization in extremely preterm infants. AB - This study reports the age at hospital discharge of 233 survivors and age at death of 209 infants who were born at 23-28 weeks gestation over a 10 year period, 1977-86. The mean duration of hospitalization of survivors was 95 days and was inversely related to maturity at birth; those born at 23-25 weeks remained in hospital on average 1-2 weeks beyond term while those born at 26-28 weeks went home on average at term or 1 week before term. The mean age at death was 12 days: 53% within 1 day, 23% between 2 and 7 days, 15% between 8 and 28 days and 9% between 28 days and 1 year. The proportions of death in the post neonatal period for infants born at 23-24 weeks, 25-26 weeks and 27-28 weeks were 2, 9 and 16% respectively. There was no significant trend in prolonged hospitalization of survivors or postponement of neonatal deaths to the post neonatal period over the 1977-86 period. Nevertheless, both neonatal and post neonatal mortality should continually be monitored in this extremely preterm group. PMID- 1888565 TI - An epidemiological survey of dog bites presenting to the emergency department of a children's hospital. AB - German shepherds are the most popular registered breed of dog in South Australia, but are also the most hazardous to children, biting more often and more severely. A study of the victims of dog bites presenting to the Emergency Department of the Adelaide Children's Hospital over an 18 month period revealed that, although many breeds were involved, only German shepherds were implicated more frequently than their prevalence in the community. Attacks occurred most often in a domestic setting involving a friendly dog that was known to the victim. Boys were more often bitten than girls and children aged 1-6 years most commonly involved. Injuries to the face and scalp were frequent and the usual ones to require admission for suture under general anaesthetic. Some scarring was a common sequel and resulting fear of dogs remained with some children. Most attacks were reported to be unprovoked and a previous biting history on the part of the dog was uncommon. Parents who are contemplating obtaining a dog for a family pet should be made aware of these facts and advised regarding the biting hazards and possible prevention. The German shepherd situation especially should be brought to their attention. PMID- 1888566 TI - Outcome to 8 years of infants less than 1000 g birthweight: relationship with neonatal ventilator and oxygen therapy. AB - The study involved a cohort of 59 consecutive survivors with birthweights less than 1000 g, born between 1977 and 1980, to 8 years of age. The aim of the report was to determine if those survivors who had received more oxygen and ventilator therapy differed in their outcome compared with those who had received less oxygen and ventilation. Children were graded into four groups, characterized by decreasing durations of oxygen and ventilation. Children who had received less oxygen and ventilation were more likely to be below the third percentile for weight at 2, 5 and 8 years but the trends were significant only at 2 and 5 years (P = 0.006, P = 0.013 and P = 0.19 respectively). The rate of cerebral palsy was 8% at 8 years; the only children with severe or moderate disabilities from their cerebral palsy were in the lowest oxygen and ventilation group (n = 4, P less than 0.02). The frequency of hospital re-admission and the duration of re hospitalization did not vary significantly between the four groups at any age. The rates of recurrent wheezing episodes or asthma did not vary significantly between the groups. Although the cohort as a whole had some impairment of lung function compared with healthy full-term controls, there was no significant difference between the four groups. Contrary to expectations, our findings suggest lower rates of poor growth and adverse neurological outcomes with increasing durations of oxygen and ventilation in the newborn period. PMID- 1888567 TI - Pitfalls in current methods of CDH detection. PMID- 1888568 TI - Neonatal meningitis. PMID- 1888569 TI - Pyloric tumour in pyloric stenosis. PMID- 1888570 TI - Postnatal chemoprophylaxis. PMID- 1888571 TI - School health services. PMID- 1888572 TI - [Mesolimbocortical dopamine system]. PMID- 1888573 TI - [Local spinal cord glucose utilization and extracellular potassium activity changes after spinal cord injury in rats]. AB - Spinal microenvironment and metabolic alterations after experimental contusional injury of the spinal cord were evaluated in the same Wistar rats. Severe spinal cord injury was made under light GOF anesthesia with a 10 g weight drop onto the exposed Th-8 spinal cord from a 10 cm height and then halothane was ceased. The author studied extracellular potassium activity ([K+]e) and DC potential for 2 hours after paraplegic spinal cord injury in conscious rats. Furthermore, at 2 hours after cord injury, local spinal cord glucose utilization (1-SCGU) was measured with quantitative autoradiographic 2-[14C] deoxy-glucose method (Sokoloff et al.). [K+]e in injured spinal cords was 59 +/- 5 (mean +/- S.E.M.) mEq at 10 min after injury and was cleared with an exponential half-life of 1 hour. At 2 hours after injury [K+]e was still high with a value of 16 +/- 1 mEq compared with 4 mEq of control animals. DC potential changes was a mirror image of that of [K+]e. DC potential changed by a mean of 10.7 mV positively from 10 min. to 2 hours after injury. 1-SCGU at the impact site was extremely low in both white and gray matters. At 6mm rostral from the impact center 1-SCGU was remarkably reduced in the gray matter, and in the lateral white matter. But at 3 mm rostral 1-SCGU was well preserved. And at 20 mm rostral there was no difference in 1-SCGU with control animals. Massive potassium efflux from the injured spinal cord to the adjacent spinal segment was clarified at this experiment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1888574 TI - [Behavioral and histochemical observation in rotational rat with adrenal medulla transplantation--comparison of two different graft sites (striatum v.s. lateral ventricle)]. AB - Effect of adrenal medullary allograft to two different sites of the brain (striatum and lateral ventricle) was compared on rotation rat. Rotation rats were prepared by chemical ablation of the right nigro-striatal system by 6-hydroxy dopamine (6-OHDA). In this experiment, adrenal medulla was transplanted to the rotation rat brain and effects of the transplantation was evaluated by behavioral change of the rats, i.e., reduction in rotation behavior, and by histochemical examination of the grafts sites, i.e., presence and morphology of dopaminergic cells. The animals were divided in to 2 groups. The first group received the graft to the striatum (striatum group) and the second group to the lateral ventricle close to the striatum (ventricle group). Six weeks after grafting, the rotation behavior in striatum group and ventricle group was reduced by 43% (p less than 0.01) and 35% (p less than 0.01) respectively as compared to that in the pretransplantation state. Twelve weeks after grafting, the comparable figures were 30% (p less than 0.05) and 17% (n.s.) respectively. Histochemical examination of graft site was similar in both groups: Six weeks after grafting, many transplanted cells transformed into nerve cells which were considered to be capable of producing dopamine and, twelve weeks after grafting, honeycomb shaped fluorescence positive area without apparent viable cells. From above results, it was concluded that the striatum was somewhat superior to the lateral ventricle as the graft site. However, the effect of the transplantation was short lasting, being most manifest at six weeks after transplantation, and started to wear off as the grafted cells perished. PMID- 1888575 TI - [Brain tumors in Yamaguchi Prefecture--incidence through 4 years]. AB - The incidence of brain tumors was studied in Yamaguchi prefecture of about 1,600,000 population. All of the brain tumor patients admitted to the neurosurgical hospitals in Yamaguchi prefecture were registered. Cases of osteoma, lipoma, scalp tumor and spinal tumor were excluded. From 1986 through 1989, 726 cases were registered. 135 recurrent cases were included. Therefore first-diagnosed primary brain tumors were selected to calculate the true incidence. The number of cases of primary brain tumor was 478 and showed female preponderance (male/female: 207/271). The incidence of primary brain tumor was 7.5/100,000/year (male/female: 6.8/8. 1). No difference was present between the incidence in cities and that in rural districts. Percentages of representative tumors were 28.2% for glioma, 32.8% for meningioma, 13.0% for pituitary adenoma and 10.7% for neurinoma. Age-adjusted incidence was 2.1/100,000/year for glioma and 2.1/100,000/year for meningioma. The incidence of glioma was lower and that of meningioma was higher in Yamaguchi prefecture than those in other reports. Compared with the Brain Tumor Registry of Japan (1969-1983), the percentage of meningioma cases was large in Yamaguchi prefecture. This difference owed partly to the increased number of population over age of 40's in Yamaguchi prefecture. The peak of age distribution was present in age of 50's in Yamaguchi prefecture and in age of 30's and 40's in Brain Tumor Registry of Japan. The peak of age distribution shifted to older ages in Yamaguchi and the difference was conspicuous in age of 60's. This peak consisted of mainly cases of meningioma and partly those of glioma.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1888576 TI - [Effects of muscle relaxant E-0646 on human stretch reflex and responses]. AB - The experiment examined the effects of a muscle relaxant E-0646 on short latency stretch reflex (SLR) and long latency stretch responses (LLRs) of lower leg muscles in 5 healthy male subjects, aged 24-41 years. An AC servomotor produced an ankle rotation of comfortably seated subjects in the direction to stretch the triceps surae muscle for the SLR and the tibialis anterior muscle for the LLRs. Following control measurements, after the oral administration of 50, 100, 150, and 300 mg of E-0646, the SLR and LLRs were recorded every 2 hours for 4 or 6 hours with simultaneous blood sampling to measure E-0646 plasma levels. Electromyograms (EMGs) of the soleus and tibialis anterior muscles were recorded with surface electrodes on each muscle belly. A precision potentiometer was used to measure the ankle angle. The soleus SLR, evoked by a torque pulse (7 msec duration) of one of 5 different amplitudes, decreased 2 hours after the 300 mg administration. A SLR decrease was also found in a simple relationship between the integrated SLR EMG and the angular velocity at 20 msec after the torque onset, in which the slope and intercept of the relationship changed. The plasma E 0646 level roughly correlated with the SLR decrease. No significant change of the SLR was observed when dosage was less than 150 mg. The LLRs of the tibialis anterior muscle were tested under the instruction "resist when perturbed" during a weak isometric contraction against a constant plantar flexion torque.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1888577 TI - [A case of Crow-Fukase syndrome associated with idiopathic thrombocytopenic purpura]. AB - A 40-year-old man was admitted to our hospital because of paresthesia and weakness of the limbs. At the age of 38, he was diagnosed as having an idiopathic thrombocytopenic purpura (ITP) which have been refractory to oral administration of prednisolone and splenectomy. Platelet-associated IgG was elevated markedly at that time. It was, however, only mildly elevated on this admission. He showed polyneuritis, generalized pigmentation, hirsutism, and marked edema on the legs. The bone X-ray disclosed a lytic lesion in the left iliac bone, which was confirmed as a plasmacytoma by bone biopsy. Axonal degeneration with marked loss of myelinated figure was seen on sural nerve biopsy. Serum immunoelectrophoresis revealed his monoclonal IgG was lambda type. Then, he was diagnosed as having a Crow-Fukase syndrome associated with ITP. Plasma exchange, pulse therapy, and irradiation to plasmacytoma resulted in a slight improvement of the polyneuritis and the skin symptoms, and a disappearance of edema. However, ITP has not responded to these therapies. Although the same autoimmune mechanism is suggested in these conditions, we could not clarify how this monoclonal IgG produce both polyneuritis and ITP. PMID- 1888578 TI - [Dissecting aneurysm of distal posterior inferior cerebellar artery--case report and review of the literature]. AB - A rare case of dissecting aneurysm of distal posterior inferior cerebellar artery (PICA) is reported. A 51-year-old woman was admitted to our hospital complaining of severe headache and nausea. CT scan revealed subarachnoid hemorrhage which was thicker in the posterior fossa. The vertebral angiography demonstrated an aneurysm on the telovelotonsillar segment (Lister's classification) of the left PICA. On the third day, the left suboccipital craniotomy was performed and the fusiform aneurysm was resected. The postoperative course was uneventful. Histological examination of the resected aneurysm showed a dissection between the ruptured elastic lamina and the tunica media. Dissecting aneurysm of distal PICA is still belong to a rare entity. In all three cases found in the literature, the dissecting aneurysms are sited in the anterior medullary segment of PICA. Probably, this is the first report described a dissecting aneurysm on the more distal part-telovelotonsillar segment of PICA. The clinical features, pathogenesis and treatment of intracranial dissecting aneurysms are briefly discussed with reviewing the literature. PMID- 1888579 TI - [A case of metoclopramide-induced neuroleptic malignant syndrome with cerebrospinal fluid lactic acidosis]. AB - A case of metoclopramide-induced neuroleptic malignant syndrome with cerebrospinal fluid (CSF) lactic acidosis was reported. A 44-year-old Japanese woman noted tarry stool on July 2, 1988 and was treated with metoclopramide and cimetidine for nausea and vomiting. Hydroxyzine pamoate was also administered for insomnia at 3:10 am and she became comatose with muscle rigidity at 3:40-4:30 am on July 3. Tachycardia and high fever (39.5 degrees C) were evident at 8:00 am on July 4. She was transferred to the Kyushu University Hospital. On admission, serum creatine kinase was elevated to 1640 IU/1; MM fraction was 100%. She was diagnosed as malignant syndrome. Cerebrospinal fluid was normocellular with protein 38 mg/dl and glucose 122 mg/dl. Cerebrospinal fluid lactate increased markedly to 3.43 mmol/l, CSF pH was 7.264, HCO3- 14.4 mEq/l, indicating CSF metabolic acidosis. She became afebrile after the 10th hospital day, and gradually but completely recovered within a month. She was discharged on August 16, 1988. The anti-dopaminergic activity of metoclopramide was considered to be primarily responsible for the development of malignant syndrome in this case. Cerebrospinal fluid lactic acidosis seemed to reflect hyperpyrexia or malignant syndrome induced derangement of the brain metabolism. PMID- 1888580 TI - The great amalgam debate. AB - Mercury amalgam has been used for dental fillings since the 1830s. Over that time, questions have occasionally been raised with regard to its safety, but a recent TV programme in America has re-focussed attention in this area. PMID- 1888581 TI - 'The health of the nation'. PMID- 1888582 TI - Science, myths and lies in dentistry. AB - Over the past 20 years there has been an explosion in the number of techniques, materials and concepts advocated for clinical dentistry. Unfortunately, this explosion is mild compared with the number of myths, falsehoods and downright lies which have accompanied these ideas. Practitioners are misinformed, and many are justifiably cynical about dental research. This article gives my opinion as to the cause of these myths together with some important ideas to constrain the problem. PMID- 1888583 TI - Specialist registration. PMID- 1888584 TI - 'A clinical trial to evaluate plaque removal with a double-headed toothbrush'. PMID- 1888585 TI - Tongue control of upper complete dentures: a clinical hint. PMID- 1888586 TI - '1931 vulcanite dentures'. PMID- 1888587 TI - Hexetidine mouthrinse in the management of minor aphthous ulceration and as an adjunct to oral hygiene. AB - A number of compounds have been used in the management of recurrent oral ulceration, including antimicrobials. This was a double-blind placebo-controlled cross-over study to assess the value of a 0.1% hexetidine mouthwash in the management of minor aphthous ulceration and as an adjunct to oral hygiene. Forty patients with a catalogued history of ulceration took part. Patients were randomly allocated to active/placebo or vice versa order of mouthwashes, which were used as 15 ml volumes three times a day. Treatment periods were 6 weeks with a 3 week washout. During each period patients kept daily records of the number, site, and duration of ulcers, together with pain scores. Plaque and gingivitis were scored at baseline and end of treatment periods. Thirty-eight patients completed the study, with no significant treatment differences between active and placebo rinses on any ulcer parameter. Additionally, the hexetidine rinse provided no significant benefit to oral hygiene or gingival health. However, there was a significant period effect, with considerable ulcer improvements during the second period, irrespective of treatment. In conclusion, the hexetidine rinse appeared to offer no benefits to these patients, but professional supervision of ulcer treatment does appear to result in a worthwhile placebo effect. PMID- 1888588 TI - Autologous keratinocyte grafting: a new technique for intra-oral reconstruction. AB - Oral keratinocytes have been grown in sheets in the laboratory from small oral biopsies from four patients undergoing reconstructive oral surgery. These sheets have been successfully applied to mucosal surfaces and good clinical results obtained, with accelerated healing of mucosal defects. These results indicate that keratinocyte grafts can be used in mucosal sites, and may have applications as an alternative to skin grafts in the mouth. PMID- 1888589 TI - Domestic water treatment appliances and the fluoride ion. AB - Specific ion metering of fluoride ion levels of water samples obtained after passage through water softeners and a conditioner showed no alteration in concentration when compared with controls. Similar comparison of water samples passed through water filters demonstrated that highly significant amounts of fluoride ion were removed. In one filter tested, 90% of the fluoride content was lost in the filtration process. The findings of this study suggest that, in a household using a filter, it may be necessary to increase the fluoride supplement or in some cases to initiate use of fluoride supplements as children are not receiving as much fluoride as was thought. New guidelines are required to take account of this surprising effect. PMID- 1888590 TI - Geographic tongue during a year of oral contraceptive cycles. AB - The geographic tongue of a 23-year-old female student was examined daily for one year. The size, number and location of the lesions were recorded using transparent films. The phase of the oral contraceptive cycle appeared to have a marked effect on the initiation and duration of the circinate lesions, the tongue changes being severest on the 17th day of the cycle. There was a positive correlation between the subjective complaint and the clinical picture of the tongue. PMID- 1888591 TI - A 10-year comparison of General Dental Service care in the Northern Region 1979 1989. AB - The 1979/1989 patterns of General Dental Service provision in the Northern Region and its nine FPC/FHSA areas have been examined in relation to intraregional variations and assessed against the national average and other regions. Attention is drawn to the Northern Region's failure to reach national averages in a number of key measures of dental care, owing to the low numbers of practitioners working within the Region. It is clear that redistribution of dental manpower will not be generated under the present system. Alternatives are required if dentistry is to continue to be an essential part of a comprehensive health service for all. PMID- 1888592 TI - A letter to hospice board members. Computers: high-tech help or old fashioned headache? PMID- 1888593 TI - The hospice movement in Poland: an appeal for help. PMID- 1888594 TI - Ethics and hospice physicians. AB - Advocates of compassionate care for the dying should contribute to the formulation of ethical policies for dealing with the dying. Having identified the relevant ethical principles and controversies there is a need for continued dialogue as society makes new demands on the medical profession. At a time when the concept of what is moral or immoral is under review, as societal mores change, the needs of the dying also change. The medical profession must be flexible in responding, within the constraints of maintaining the integrity of the profession. PMID- 1888595 TI - It takes more than knowledge: it takes assertiveness. PMID- 1888596 TI - Grief has no color. PMID- 1888597 TI - Utilization review of hospice: an interdisciplinary team approach. PMID- 1888598 TI - When Mommy dies. PMID- 1888599 TI - Understanding tolerance, physical dependence and addiction in the use of opioid analgesics. PMID- 1888600 TI - Fluid and electrolytes revisited. PMID- 1888601 TI - Is postoperative oliguria avoidable? PMID- 1888602 TI - Management of hyponatraemia. PMID- 1888603 TI - Calcium for resuscitation? AB - Calcium ions are essential for myocardial excitation-contraction coupling and for increasing contractility of the heart. Because of these physiological effects, use of calcium has been recommended in the treatment of electromechanical dissociation, asystole and ventricular fibrillation. Recently, however, the use of calcium during cardiac arrest has come into dispute, as there are no controlled clinical trials supporting a favourable haemodynamic effect. It has rather been suggested that, in resuscitation, calcium may have detrimental effects. In order to evaluate the role of calcium in cardiopulmonary resuscitation, it is important to know the serum concentrations of calcium and the haemodynamic effects in this situation. Measurements in some patients with cardiac arrest have demonstrated that severe hypocalcaemia may not be uncommon. In these patients, calcium may augment myocardial contractility, decrease intracardiac filling pressures and increase mean arterial pressure. At present, the more or less established indications for use of calcium during cardiopulmonary resuscitation are in treating patients with proven hypocalcaemia, hyperkalaemia, calcium channel blocker overdose and, possibly, electromechanical dissociation combined with a wide QRS complex. There is no good evidence supporting the routine use of calcium in resuscitation. PMID- 1888604 TI - Fluids for resuscitation. PMID- 1888605 TI - Proceedings of the Anaesthetic Research Society, Exeter meeting. March 22-23, 1991. Abstracts. PMID- 1888606 TI - Relationship between exercise-induced myolysis and malignant hyperthermia. PMID- 1888607 TI - 29-gauge spinal needles. PMID- 1888608 TI - Tension pneumothorax--wrong tube? PMID- 1888610 TI - Uncertainties about the ventilatory response to hypoxaemia. PMID- 1888609 TI - Inappropriate heparinization with a cell saver. PMID- 1888611 TI - Failed tracheal intubation. PMID- 1888612 TI - Tracheal intubation with the patient in a sitting position. PMID- 1888613 TI - Analgesia with subhypnotic doses of thiopentone and propofol. PMID- 1888614 TI - Incremental spinal anaesthesia and caesarean section--relevance to the test dose for extradural analgesia. PMID- 1888615 TI - The scope of clinical pharmacology in the pharmaceutical industry. PMID- 1888616 TI - The roles and responsibilities of clinical pharmacology. PMID- 1888617 TI - Pharmacokinetic and pharmacodynamic effects of UK-68,798, a new potential class III antiarrhythmic drug. AB - 1. The pharmacokinetic and pharmacodynamic properties of UK-68,798, a novel selective potential class III antiarrhythmic agent, were studied in 18 patients with coronary artery disease. Three groups of four patients received intravenous doses of 1.5, 3.0 and 4.5 micrograms kg-1 respectively over 10 min. 2. UK-68,798 caused a mean increase in electrocardiographic QTc interval of 41, 40 and 81 ms, and in uncorrected QT interval of 36, 52 and 83 ms at the three dose levels. There were no significant effects on heart rate, blood pressure, PR interval and QRS duration. UK-68,798 was well tolerated with no significant adverse effects. 3. A dosing regimen using a loading infusion of two thirds of the total dose over 15 min with the remainder given over the following 45 min in six patients produced stable plasma concentrations and lengthening in QTc during the maintenance infusion. 4. There was a linear correlation between plasma concentration and change in QTc. The drug exhibited first-order kinetics with a mean clearance of 4.7 +/- 1.2 ml min-1 kg-1 and a mean terminal plasma half-life of 9.7 h. 5. UK-68,798 warrants further study as a selective potential Class III antiarrhythmic agent. PMID- 1888618 TI - The effect of intra-arterial endothelin on resting blood flow and sympathetically mediated vasoconstriction in the forearm of man. AB - 1. The hypothesis that endothelin (ET) influences sympathetically mediated vasoconstriction was investigated in 13 healthy, male subjects. 2. ET (1 pmol min 1) was infused for 60 min into the left brachial arteries of seven healthy male subjects. Resting forearm blood flow, and sympathetic vasoconstriction produced by lower body negative pressure (LBNP; 15 mm Hg), was measured in both arms by strain gauge plethysmography. In a further six subjects, noradrenaline (NA) was infused intra-arterially at doses of 150-600 pmol min-1, with and without co infusion of ET (1 pmol min-1), with blood flow measured in both forearms. 3. ET produced a small but significant reduction of blood flow in the infused forearm from 3.9 +/- 0.6 ml 100 ml-1 min-1 during infusion of saline, to 3.3 +/- 0.7 ml 100 ml-1 min-1 during infusion of ET at 60 min (P less than 0.05). Blood flow in the non-infused forearm was not altered by ET infusion. 4. NA produced a significant and dose-dependent reduction of blood flow in the infused forearm from 3.13 +/- 0.5 ml 100 ml-1 min-1 during saline infusion, to 1.49 +/- 0.2 ml 100 ml-1 min-1 with NA at 600 pmol min-1 (P less than 0.001). During co-infusion of ET, blood flow was reduced similarly in the infused arm from 3.15 +/- 0.7 ml 100 ml-1 min-1 during saline infusion to 1.55 +/- 0.2 ml 100 ml-1 min-1 with NA at 600 pmol min-1. Blood flow in the non-infused arm was not altered by ET and NA infusion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1888619 TI - Evaluation of drug information for cardiology patients. AB - 1. Cardiologists and pharmacists at the University Hospital of Wales collaborated to write 20 individual leaflets incorporating guidelines for a range of drugs used in the treatment of cardiology patients. The Plain English Campaign advised on the intelligibility and presentation of the information. 2. One hundred and twenty-five patients from the Regional Cardiology Unit, University Hospital of Wales were randomly allocated to receive usual verbal counselling about their drug treatment with or without an individualised drug information wallet. Two weeks after discharge from hospital patients completed a postal questionnaire to determine their satisfaction with the information about their drug treatment and their understanding of it. Forty-nine questionnaires were returned from the leaflet group and 52 from the control group. 3. The provision of written guidelines resulted in significant improvements in patients' satisfaction with their drug treatment (chi 2 = 33.3, P less than 0.001) and their understanding of it (P less than 0.001, Mann-Whitney test). Overall, patients who received leaflets were more likely to be aware of the potential side effects of their drugs but less likely to be apprehensive about them. Succinct guidelines concerning drug therapy can be assimilated by cardiology patients and provide them with a permanent record for future reference. PMID- 1888620 TI - Lack of a relationship between the polymorphism of debrisoquine oxidation and lung cancer. AB - 1. Determination of debrisoquine oxidation phenotype was carried out in 119 healthy subjects, 135 patients with chronic bronchitis and 153 patients with lung cancer, all of Caucasian origin. 2. A non-Gaussian distribution of the log D/HD ratio was observed in the three groups. 3. Assuming an antimode of 1.12, the proportion of PMs was found to be 6.7% in healthy subjects, 8.9% in chronic bronchitics and 6.5% in patients with lung cancer. These differences were not significant. 4. The presence of a lung tumour itself had no influence on phenotype in a group of 14 patients who were phenotyped before and after surgery. 5. We conclude that a link between debrisoquine phenotype and lung cancer is unlikely. PMID- 1888621 TI - Diclofenac concentrations in synovial fluid and plasma after cutaneous application in inflammatory and degenerative joint disease. AB - 1. Ten patients with bilateral knee joint effusions were treated topically with a gel containing 1 g diclofenac/100 g (80 mg three times daily). They were randomized to receive diclofenac gel to one knee and a placebo gel preparation to the other knee. 2. Diclofenac was assayed in synovial fluid and blood plasma by GC/ECD as the pentafluorobenzyl-ester derivative. 3. Total concentrations of diclofenac in synovial fluid (day 4) were significantly higher in the diclofenac gel treated knee than in the contralateral placebo treated knee (25.5 +/- 3.6 ng ml-1 vs 21.6 +/- 2 ng ml-1; P less than 0.05). These concentrations were lower than total plasma drug concentrations (40.6 +/- 4.7 ng ml-1, n = 10, P less than 0.01). Unbound concentrations of diclofenac in synovial fluid from either the diclofenac gel treated or the placebo treated knee were not significantly different from each other or from plasma free concentrations (115 +/- 16 and 99 +/- 12 vs 108 +/- 19 pg ml-1). 4. Clinical parameters showed improvement of joint mobility and a small reduction of swelling (circumference) in both knees with time. However, the differences between knees were not significant. 5. We conclude that direct transport of diclofenac from the skin into the ipsilateral knee joint after cutaneous application is minimal. Distribution seems to be predominantly via the blood. Whether the observed improvements of clinical parameters were due to drug effects or to the spontaneous course of the underlying disease cannot be distinguished. PMID- 1888622 TI - The comparative pharmacokinetics of acemetacin in young subjects and elderly patients. AB - Single and multiple dose pharmacokinetics of acemetacin in 10 young healthy subjects and 10 elderly patients with osteoarthritis were studied. Peak plasma concentrations of acemetacin and its metabolite, indomethacin, were found between 2.4 and 4 h after an oral dose of the drug. After dosing to steady state (7 days), the mean plasma elimination half-life for acemetacin was 1.1 h and 1.0 h, and for indomethacin 7.1 h and 7.2 h in the young and elderly groups respectively. Statistical analysis of tmax, AUC, plasma t1/2 and residual drug concentrations for acemetacin or indomethacin revealed no significant differences (P greater than 0.05) between young subjects and elderly patients after acute or chronic dosing. The results suggest that drug accumulation did not occur in the elderly subjects over the time period studied and that, on pharmacokinetic grounds, dose adjustment in the elderly is unlikely to be required. PMID- 1888623 TI - Diflunisal and its conjugates in patients with renal failure. AB - Six patients with renal failure were given a single oral dose (250 mg) of diflunisal. In contrast to the acyl glucuronide, the phenolic glucuronide and sulphate conjugates showed the capacity to accumulate in plasma, suggesting that systemic instability of the acyl glucuronide contributes, via hydrolysis, to plasma concentrations of diflunisal itself. Although earlier studies in renal failure patients have almost certainly underestimated diflunisal clearance (by overestimation of plasma diflunisal concentrations through unrecognized acidic hydrolysis of diflunisal sulphate during analysis), the present results suggest that the reported decrease in clearance was not attributable only to this analytical artifact. PMID- 1888624 TI - A comparison of drug protein binding and alpha 1-acid glycoprotein concentration in Chinese and Caucasians. AB - alpha 1-acid glycoprotein (AAG) concentration and the binding of both lignocaine and warfarin were compared in 15 healthy Chinese and age and sex matched Irish (Caucasian) subjects. Both the extent of lignocaine binding and AAG concentrations were significantly (P less than 0.05) lower in Chinese subjects. No difference was shown in warfarin binding. These results suggest that the binding of basic drugs may be significantly less in Chinese than Caucasians, and lower concentrations of the binding protein AAG are a major determinant of this difference. PMID- 1888625 TI - A comparison of serum and saliva paracetamol concentrations. AB - The relationship between serum and saliva paracetamol concentrations was investigated in twenty healthy volunteers. The plasma and saliva drug concentrations showed a significant correlation (r = 0.67). However the agreement between the two methods of measurement was poor with limits of agreement of -15.3 mg l-1 to +15.9 mg l-1 with mean sample values of 19.2 and 19.5 mg l-1 for plasma and saliva, respectively. PMID- 1888626 TI - Mefloquine pharmacokinetics and resistance in children with acute falciparum malaria. AB - The pharmacokinetic properties of mefloquine hydrochloride (15 mg base kg -1) were studied in 12 Karen children (five girls, seven boys) aged between 5 and 10 years presenting with uncomplicated falciparum malaria. The drug was well tolerated. Mean (s.d.) peak blood drug concentrations of 2031 (831) ng ml-1 were reached in a median of 8 (range 6-24) h. Mean (s.d.) estimates for oral clearance and mean residence time were 0.52 (0.27) ml min -1 kg -1 and 15.3 (4.7) days, respectively. These values are similar to those reported previously in adults. In one child parasitaemia failed to clear despite whole blood mefloquine concentrations which peaked at 1744 ng ml -1; parasitaemia rose and fever recurred when blood drug concentrations had fallen to 442 ng ml -1. The prevalence of highly mefloquine resistant parasites such as this can be expected to increase under drug pressure in this area. PMID- 1888627 TI - Should we cross off the crossover? PMID- 1888628 TI - Stereoselective pharmacokinetics of oral and intravenous nitrendipine in healthy male subjects. AB - 1. Stereoselectivity in the pharmacokinetics of nitrendipine was investigated by reanalysing plasma samples of a previously published study (Soons et al., 1989). 2. Racemic nitrendipine was administered intravenously (40 micrograms kg-1) and orally, both as plain tablet (20 mg) and in an osmotic pump device (40 mg Osmet) to nine healthy male subjects. Nitrendipine enantiomers were measured with a stereoselective assay. 3. Upon oral administration (tablet) the bioavailability of (S)-(-)-nitrendipine (13.4% +/- 5.6%) was 75% (50% - 98%) higher than that of (R)-nitrendipine (7.9% +/- 4.0%) (mean +/- s.d. (95% confidence interval)). Values of AUC and Cmax for (S)-nitrendipine were 90% (55% - 121%) and 77% (51% - 100%) higher respectively, than those for (R)-nitrendipine. Similar results were obtained with the osmotic system. 4. The clearance of intravenously administered (S)-nitrendipine was slightly (7%) lower than that of (R)-nitrendipine, but elimination half-lives and volumes of distribution were similar. 5. The difference in disposition of nitrendipine enantiomers is most likely related to a difference in activity of the cytochrome P-450 system towards the enantiomers, giving rise to a two-fold difference in first-pass elimination. 6. Stereoselectivity in the first pass metabolism of nitrendipine exhibited little intersubject variability and therefore is not a major factor in the wide variability in systemic availability of the more-potent (S)-enantiomer. PMID- 1888630 TI - Once vs twice daily administration of a fixed combination of captopril plus hydrochlorothiazide in essential hypertension: a double-blind crossover study in known responders to a standard combination. AB - The purpose of this randomized, double-blind, crossover trial was to compare the hypotensive effects of a fixed combination of captopril (C) 50 mg and hydrochlorothiazide (HCTZ) 25 mg (C 50/HCTZ 25) once daily with those of a fixed combination of C 25 mg and HCTZ 12.5 mg (C 25/HCTZ 12.5) twice daily. We studied 199 patients (108 M, 91 F) with mild to moderate essential hypertension whose BP was already controlled by the co-administration of C 25 mg and HCTZ 12.5 mg twice daily. They were randomly assigned to either C 25/HCTZ 12.5 twice daily during the first 6 weeks and C 50/HCTZ 25 once daily during the second 6 weeks or C 50/HCTZ 25 once daily followed by C 25/HCTZ 12.5 twice daily. Both regimens showed comparable efficacy on office diastolic BP (91.6 vs 91.3 mm Hg). Systolic BP was slightly but significantly higher (P = 0.02) with the once daily formulation (141.2 vs 139.1 mm Hg). Fixed combinations once daily and twice daily resulted in identical working ambulatory BP (133.7 +/- 13/83.6 +/- 8 mm Hg vs 132.4 +/- 11/83.3 +/- 7 mm Hg) without affecting heart rate. Adverse events were reported by 16% of patients and cough was the most common occurring in 7%. In conclusion, these results indicate that the fixed combination of C 50/HCTZ 25 given once daily controls office and working BP as well as the fixed combination C 25/HCTZ 12.5 given twice daily in patients with mild to moderate hypertension. PMID- 1888629 TI - Regular nebulised terbutaline in chronic obstructive airways disease: dose response studies fail to detect tolerance. AB - 1. To determine the effects of high dose terbutaline on the possible development of tolerance we have examined the influence on dose-response of regular nebulised terbutaline. 2. We studied 10 subjects with severe chronic obstructive airways disease (COAD), mean age 63 years mean (s.e. mean) PEFR 142 l min-1 (19), FEV1 0.77 1 (0.12) and FVC 1.93 (0.19). Cumulative dose-response curves were measured (PEFR, FEV1 and FVC) to six incremental doses of terbutaline (0.5-8 mg) before and 1, 4, 8 and 12 weeks after starting nebulised terbutaline 5 mg four times a day. 3. Maximal bronchodilatation (Emax) was calculated by polynomial regression. Responses were examined by analysis of variance. 4. Mean baseline PEFR increased by 32 l min-1 (P less than 0.05), FEV1 by 0.16 1 (NS) and FVC by 0.54 l (P less than 0.05) after 12 weeks. Initial mean Emax PEFR was maintained throughout the study. The percentage of mean Emax PEFR achieved by each cumulative dose of terbutaline either increased (0.5 mg, 1 mg and 2 mg, P less than 0.01) or was maintained (4 mg, 6 mg and 8 mg) throughout the study. 5. We conclude that in severe COAD regular nebulised terbutaline 5 mg four times a day produces a sustained improvement in baseline lung function without changes in dose-response which would suggest tolerance. PMID- 1888631 TI - The effect of preincubation with cimetidine on the N-hydroxylation of dapsone by human liver microsomes. AB - We have examined the ability of cimetidine to inhibit the oxidative metabolism and hence haemotoxicity of dapsone in vitro, using a two compartment system in which two Teflon chambers are separated by a semi-permeable membrane. Compartment A contained a drug metabolizing system (microsomes prepared from human or rat liver +/- NADPH), whilst compartment B contained human red cells. Preincubation (30 min) of human liver microsomes with cimetidine (0-1000 microM) and NADPH prior to the addition of dapsone (100 microM) and NADPH (1 mM) resulted in a concentration-dependent decrease in the concentrations of dapsone hydroxylamine (from 179 +/- 47 to 40 +/- 6 ng) in compartment B. This reduction of hydroxylamine metabolite was reflected in the concentration-dependent reduction in methaemoglobin measured (from 7.1 +/- 0.7 to 3.5 +/- 1.5%) in parallel experiments. Preincubation of microsomes with cimetidine in the absence of NADPH had no effect. The effect of cimetidine pretreatment on dapsone-dependent methaemoglobin was confirmed using microsomes prepared from a further three sources of human liver, as well as from rat liver. PMID- 1888632 TI - Lack of effect of flosequinan on the pharmacokinetics of theophylline. AB - The pharmacokinetics of theophylline (240 mg) p.o. were studied before and after the administration of oral flosequinan for 14 days in 21 healthy volunteers using a randomised cross-over design. Comparisons of Cmax, tmax, AUC, CL of theophylline and urinary recovery of the parent drug and metabolites showed that flosequinan had no significant effect on the disposition of theophylline. PMID- 1888634 TI - Cyclosporin A does not possess K+ channel opening properties in smooth muscle. PMID- 1888633 TI - COMT inhibition with nitecapone does not affect the tyramine pressor response. AB - Nitecapone (OR-462) is a new selective COMT inhibitor with gastroprotective properties. The aim of the present study was to determine whether nitecapone potentiates the haemodynamic effects of a tyramine-induced increase in catecholamine release. The systolic blood pressure response to tyramine was studied in 11 healthy male volunteers (age 20-32 years). Tyramine was given i.v. as rapid bolus injections in increasing doses without drug intake and after oral intake of single doses of 25 mg and 100 mg of nitecapone. The tyramine dose required to increase systolic blood pressure by 30 mm Hg ('pressor dose') was 4.98 mg, 5.04 mg and 4.88 mg after no medication, and with 25 mg and 100 mg of nitecapone, respectively. There were also no differences in the systolic blood pressure response vs time curves between the three regimens. COMT inhibition with nitecapone did not potentiate the haemodynamic responses to tyramine-induced catecholamine release. PMID- 1888635 TI - Distinct phenotypes and genotypes of debrisoquine hydroxylation among Europeans and Chinese. PMID- 1888636 TI - Fluoxetine and norfluoxetine are potent inhibitors of P450IID6--the source of the sparteine/debrisoquine oxidation polymorphism. PMID- 1888637 TI - The lateral decubitus position may affect gastric emptying through an autonomic mechanism: the skin pressure-vegetative reflex. PMID- 1888639 TI - Morphine kinetics after diamorphine infusion in premature neonates. AB - 1. The pharmacokinetics of morphine were studied in 26 newborn premature neonates (26-38 weeks gestational age) who were given a loading dose of 50 micrograms kg-1 of diamorphine followed by an intravenous infusion of 15 micrograms kg-1 h-1 of diamorphine. Plasma concentrations of morphine were measured during the infusion at steady-state and for 24 h after the cessation of the diamorphine infusion. 2. The mean steady-state plasma morphine concentration (+/- s.d.) for a diamorphine infusion rate of 15 micrograms kg-1 h-1 was 62.5 +/- 22.8 ng ml-1. 3. Morphine clearance was 3.6 +/- 0.9 ml min-1 kg-1, the elimination half-life was 8.9 +/- 3.3 h and the volume of distribution was 2.7 +/- 1.01 kg-1. 4. Morphine elimination kinetics were described by a mono-exponential function. 5. There was a direct relationship between the gestational age of the patients and the clearance (r2 = 0.31, P = 0.003) and half-life (r2 = 0.35, P = 0.01) of morphine, but no relationship was found between gestational age and volume of distribution. 6. The results suggest that the currently used dosing regimen of diamorphine achieves a safe and effective morphine concentration in the premature newborn but that the loading dose could be modified to achieve a more rapid onset of analgesia. PMID- 1888638 TI - Possible pharmacological actions of magnesium in acute myocardial infarction. PMID- 1888640 TI - The effect of infinitesimal drug dilutions on the pharmacokinetics of nalidixic acid and atenolol. AB - 1. Ten healthy subjects received two treatments: a single 1 g oral dose of nalidixic acid (NA) followed 1 h later by either an infinitesimal dilution of the drug (NA 7CH) or by succussed water which served as placebo. The study was repeated 18 months later in 10 different subjects. 2. A further 10 healthy subjects received three treatments: a single 100 mg oral dose of atenolol (AT) followed 3 h later by either placebo or a dilution of AT (AT 7CH) or of bisoprolol (BI 7CH). The homoeopathic preparations were administered by the sublingual route. 3. In the first NA experiment NA 7CH significantly shortened the elimination half-life of NA from 8.6 +/- 2.2 (placebo) to 6.4 +/- 1.6 h (NA 7CH). In the second NA experiment none of the pharmacokinetic parameters was modified significantly by the administration of NA 7CH. Neither AT 7CH nor BI 7CH modified the pharmacokinetics of AT. PMID- 1888641 TI - Cardiovascular effects of cromakalim (BRL 34915) in healthy volunteers. AB - 1. The effect of oral doses of cromakalim 0.5, 1.0, 1.5 and 2.0 mg on several cardiovascular parameters was studied in healthy male volunteers. 2. In the first study, no dose of cromakalim reduced systolic or diastolic blood pressure in the supine or standing position. Reductions of diastolic blood pressure after exercise (P less than 0.01) were observed 4 h after administration of 2.0 mg. 3. There was a trend towards increased heart rate after 2.0 mg at all time intervals, and significant changes were observed in supine and standing heart rate at 2 and 4 h (P less than 0.01). No significant change was observed in exercise heart rate. 4. In the second study small increases in forearm blood flow were observed from 3 h to 5 h after oral administration of 1.0 and 2.0 mg of cromakalim. Forearm vascular resistance was significantly reduced after 2.0 mg (P less than 0.025) when compared with placebo. No change was observed in forearm venous capacitance after either dose of cromakalim, or placebo. Supine heart rate was significantly increased 4 h after 2.0 mg of cromakalim (P less than 0.025). 5. These results show that oral administration of cromakalim decreases diastolic blood pressure and forearm vascular resistance. A hypotensive effect is probably attenuated by reflex tachycardia. PMID- 1888642 TI - Inhibitory effect of uraemia on the hepatic clearance and metabolism of nicardipine. AB - 1. The principal aim of this study was to investigate the effect of renal impairment on the pharmacokinetics of nicardipine following intravenous and oral dosing. 2. The plasma clearance of nicardipine was significantly lower at 6.5 ml min-1 kg-1 in patients with impaired renal function, compared with a mean value of 10.4 in patients with normal renal function and with 12.5 ml min-1 kg-1 in patients on regular haemodialysis treatment. 3. In comparison to the patients with normal renal function, there were significant increases in AUC and Cmax in the patients with renal impairment. These increases were particularly marked during chronic dosing - AUC was increased by 163%, Cmax by 127% and apparent oral bioavailability by 90%. There were no such increases in the dialysis group whose values were similar to those for normal renal function. 4. There were no significant differences in volume of distribution or protein binding, nor in the measured indices of hepatic function to account for the reduction in drug clearance in the patients with renal impairment. 5. The results of this study indicate that renal impairment may have a significant and potentially important impact on the disposition of a drug which, under normal circumstances, is highly extracted by the liver. Accumulation of a metabolic 'inhibitor' substance is a possible explanation. PMID- 1888643 TI - No effect of probenecid on the renal and biliary clearances of digoxin in man. AB - 1. The cardiac glycoside digoxin is subject to a number of pharmacokinetic interactions. This study concerns the influence of the anionic transport inhibitor probenecid on the steady-state kinetics of digoxin. 2. Six healthy young men were enrolled in the study. After an administration period of 6 days with digoxin only (0.5 to 1 mg p.o. day-1) or digoxin in combination with probenecid (2 g p.o. day-1; 8 days), digoxin was administered intravenously (0.7 oral dose) on day 7. Plasma and urine samples were taken over 48 h. The biliary clearance of digoxin was measured during day 8 by a duodenal perfusion technique. 3. Probenecid did not affect the plasma clearance (mean +/- s.d.: 255 +/- 80 vs 266 +/- 40 ml min-1), renal clearance (166 +/- 17 vs 155 +/- 10 ml min-1), biliary clearance (106 +/- 40 vs 111 +/- 50 ml min-1), elimination half-life (34.4 vs 35.2 h) or volume of distribution (538 +/- 241 vs 566 +/- 60 l) of digoxin. 4. Our results suggest that different systems exist in man for the renal and biliary secretion of probenecid and digoxin. PMID- 1888644 TI - Dose-related analgesic effects of flupirtine. AB - 1. Flupirtine is a novel and, in all probability, centrally acting, analgesic. The present investigation was conducted in order to investigate dose-related effects of perorally administered flupirtine in man, with special regard to specifically analgesic actions, employing a model based on pain-related chemosomatosensory evoked potentials and subjective intensity estimates of painful stimuli. 2. Plasma concentrations of flupirtine measured 2 h after dosing linearly increased as a function of the administered dose. 3. It was possible to reproduce our own previously obtained results, which established the analgesic action of 200 mg flupirtine administered perorally. 4. Intensity estimates linearly decreased as a function of the administered dose, whereas chemosomatosensory evoked potential amplitudes non-linearly changed in relation to the administered dose. 5. In the spontaneous EEG, a dose-dependent increment in the power-spectra was observed, and this mainly in the alpha- and beta-range. PMID- 1888647 TI - The morphology and function of echocardiography. AB - Ultrasonographic methods rely on piezoelectric effects that define the reflection of sound energy from either moving blood or tissue. Noninvasive imaging of cardiac structures has altered the practice of cardiology over the past decade. During recent years, Doppler echocardiography has brought important advances in the assessment of cardiac morphology and function. Doppler color flow mapping studies have greatly enhanced both structural and functional assessment and the evaluation of congenital and acquired cardiac diseases. Although two-dimensional echocardiography is an established tool in clinical cardiology, the image quality of conventional transthoracic approaches can sometimes be unsatisfactory for various reasons. In such cases, transesophageal echocardiography can provide important diagnostic information. Furthermore, some structures that are poorly visualized on standard precordial echocardiography can be observed better on the transesophageal approach. PMID- 1888645 TI - Aspirin-induced gastric mucosal damage: prevention by enteric-coating and relation to prostaglandin synthesis. AB - 1. Gastric damage induced by low-dose aspirin and the protective effect of enteric-coating was assessed in healthy volunteers in a double-blind placebo controlled cross-over trial using Latin square design. Each was administered placebo, plain aspirin 300 mg daily, plain aspirin 600 mg four times daily, enteric-coated aspirin 300 mg daily, or enteric-coated aspirin 600 mg four times daily for 5 days. Gastric damage was assessed endoscopically, and gastric mucosal bleeding measured. 2. Aspirin 300 mg daily and 600 mg four times daily caused significant increases in gastric injury compared with placebo. Gastric mucosal bleeding was significantly more with the high dose, with a trend towards increased gastric erosions, compared with the low dose. 3. Enteric-coating of aspirin eliminated the injury caused by low dose aspirin and substantially reduced that caused by the higher dose. 4. All dosages and formulations caused similar inhibition of gastric mucosal prostaglandin E2 synthesis. 5. Serum thromboxane levels were suppressed equally with plain and enteric-coated aspirin. 6. In this short-term study in healthy volunteers, gastric toxicity from aspirin was largely topical, independent of inhibition of prostaglandin synthesis, and could be virtually eliminated by the use of an enteric-coated preparation. PMID- 1888646 TI - Monotherapy with conventional and controlled-release carbamazepine: a double blind, double-dummy comparison in epileptic patients. AB - 1. Twenty-one epileptic patients completed a double-blind, double-dummy, random order, crossover comparison of conventional carbamazepine (CBZ, Tegretol, Ciba Geigy) with a new controlled-release formulation (CBZ-CR, Tegretol Retard). All participants were stabilised on maximally tolerated doses of CBZ as monotherapy (one twice daily, twelve three times daily, eight four times daily). Each preparation was taken with a matched placebo of the other for 4 weeks. 2. Peak serum CBZ concentrations (mean +/- s.e. mean) were lower (CBZ 11.4 +/- 0.4 mg l 1; CBZ-CR 10.4 +/- 0.5 mg l-1; P less than 0.01) and times to peak longer (CBZ 3.6 +/- 0.5 h, CBZ-CR 5.2 +/- 0.7 h, P less than 0.01) during CBZ-CR treatment. Mean CBZ concentrations, however, were also slightly reduced with the new formulation (CBZ 9.9 +/- 0.3 mg l-1; CBZ-CR 9.1 +/- 0.5 mg l-1, P less than 0.05) and this was associated with greater seizure frequency (CBZ 2.8 +/- 1.2, CBZ-CR 3.8 +/- 0.9; P less than 0.05) during the CBZ-CR treatment phase. 3. Diurnal fluctuations (CBZ 41 +/- 3%, CBZ-CR 28 +/- 2%, P less than 0.01) and variations (CBZ 53 +/- 5%, CBZ-CR 33 +/- 3%; P less than 0.01) in serum CBZ concentration were substantially less with CBZ-CR and were similar to those calculated during a 6 or 8 hourly dosage interval with conventional CBZ (fluctuation 33 +/- 3%, variation 42 +/- 5%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1888648 TI - Magnetic resonance imaging of the heart: perfusion, function, and structure. AB - The use of interventional therapy in acute myocardial infarction has intensified the desire to obtain accurate information on regional myocardial perfusion. MR imaging using ultrafast techniques and contrast agents may be useful to estimate myocardial perfusion in patients with coronary artery disease. In addition, MR imaging with contrast agents is capable of defining the infarcted region and the area at risk after coronary artery occlusion. Quantitative evaluation of regional myocardial contractile function with and without pharmacologic stress testing further improves the utility of MR imaging in defining the effects of reperfusion therapy on dysfunctional myocardium and in detecting myocardial ischemia. Furthermore, cine MR techniques are now used extensively to assess cardiac function and volumes and to obtain flow velocity maps. Cardiac MR applications are evolving rapidly and the clinical significance is expanding. PMID- 1888649 TI - Evaluation of great heart vessels and pulmonary vasculature. AB - This year's literature relating to imaging of the great heart vessels was devoted primarily to measurements of aortic size and to comparisons of imaging modalities in evaluating aortic aneurysms, dissections, and coarctation. The imaging modalities compared were plain chest roentgenography, conventional CT, ultrafast CT, MR imaging, transcutaneous esophageal echocardiography, and Doppler echocardiography. The pulmonary vasculature literature dealt with MR imaging of pulmonary vessels and the estimations of pulmonary pressure using echocardiography and Doppler techniques. PMID- 1888650 TI - Evaluation of systolic and diastolic heart function. AB - The evaluation of cardiac function generated considerable interest in the 1990 literature. Conventional modalities such as contrast angiography, cardiac ultrasound, and radionuclide angiography are being applied in new ways to the investigation of both systolic and, especially, diastolic heart function. Ultrafast CT can be used to precisely quantitate ventricular volumes and ejection fraction. Similarly, spin-echo and cine MR imaging provide accurate estimates of both global and regional ventricular function. However, the high cost of these sophisticated imaging modalities may limit their use for the routine assessment of systolic heart function. PMID- 1888651 TI - Evaluation of congenital diseases of the heart. AB - Three different new developments have taken place in the evaluation of congenital heart diseases. First, in the fetal period, intravaginal echocardiography allows earlier diagnosis of significant cardiac abnormalities that could lead to a wanted termination of pregnancy. Second, in adults and children, MR imaging has become a standard imaging modality in complex congenital heart diseases. Moreover MR imaging has become the best noninvasive imaging method in visualization of the great vessels. Finally, in surgery, the intraoperative epicardial echocardiography could improve operation results in the future (solving the regurgitation problem). Postoperatively, MR imaging has become an important diagnostic tool that helps to reduce repeated catheterization and angiography. PMID- 1888652 TI - Coronary angiography and interventional cardiology. AB - The purpose of coronary arteriography is to image the pathoanatomic morphology fundamental to diagnosis and therapy. Interventional cardiology aims to eliminate the pathologic substrate as completely as possible. The interventional techniques and the assessment of their success are based on an exact geometric and, in particular, functional analysis of coronary artery stenoses. Recent progress in coronary arteriography has involved, firstly, quantification of structural and functional aspects. Secondly, the direct application of the information provided, which permits immediate diagnosis and treatment, demands real-time availability and maximum quality, especially for imaging difficult geometric conditions. PMID- 1888654 TI - Mammographic equipment, technique, and quality control. AB - The most important improvements in mammographic technique were the introduction of single- or double-emulsion high-contrast film-screen combinations for mammography, the use of a specially designed low-kilovoltage Bucky grid to reduce scattered radiation, and the introduction of smaller focal spots to improve imaging geometry. Magnification techniques, especially the spot-film technique, yields clearer delineation of high-contrast microcalcifications. Dedicated mammographic equipment with specially designed x-ray tubes is necessary for modern high-quality mammography. However, in many modern mammographic units, the automatic exposure controller still fails to provide appropriate and constant optical film density over a wide range of tissue thickness and absorption. Extended-cycle processing of single-emulsion mammographic films can yield better image contrast and reduce exposure by up to 30%. Exposure times of less than 1 second are recommended to avoid the unnecessary higher doses caused by longer exposure times and reciprocity law failure. The wide dynamic range in mammography can be reduced by a beam equalization filter, and thus be better adapted to the decreased latitude of modern high-contrast mammographic screen-film systems. Mammographic film reading (detection of subtle microcalcifications) can be facilitated by modern computer evaluation of previously digitized mammograms. Standardization and assurance of image quality have been major challenges in the technical development of mammography. Different technical and anthropomorphic phantoms have been designed to measure and compare practical image quality. Detailed quality control measures have been developed. The benefit of a single or annual screening mammography, calculated in gained life expectancy, by far outweighs the relative risk for radiation-induced breast cancer. PMID- 1888653 TI - Nuclear cardiology: myocardial perfusion and function. AB - Myocardial perfusion studies continue to be a major focus of research, with new investigations of the relationship of exercise-redistribution thallium imaging to diagnosis, prognosis, and case management. The redistribution phenomenon, which seemed to be fairly well understood a few years ago, is now recognized to be much more complex than originally thought, and various strategies have been proposed to clarify the meaning of persistent defects. Pharmacologic intervention with dipyridamole and adenosine has become available as an alternative to exercise, and comparisons with exercise imaging and catheterization results have been described. Thallium itself is no longer the sole single-photon perfusion radiopharmaceutical; two new technetium agents are now widely available. In addition to perfusion studies, advances in the study of ventricular function have been made, including reports of studies performed in conjunction with technetium perfusion studies, new insights into cardiac physiology, and the prognostic and case-management information that function studies provide. Finally, work has continued with monoclonal antibodies for the identification of areas of myocyte necrosis. PMID- 1888655 TI - Follow-up as an alternative to biopsy for probably benign mammographically detected abnormalities. AB - As utilization of mammographic screening increases, a large number of probably benign mammographic abnormalities are being reported. Although the primary effort of screening mammography is to detect cancer at its earliest stages, the secondary goal must be to recognize probably benign abnormalities as such and to offer prudent alternative strategies to surgical excision. Retrospective studies of false-negative mammographic findings indicated the potential for increased sensitivity of employing subthreshold findings. But this increased sensitivity is at a high cost of appropriated resources. Other retrospective studies suggested that such increased sensitivity may not be translated to improved clinical outcome. The validity of mammographic surveillance as opposed to immediate surgical referral is best evaluated through prospective trials. Three such trials have been published in the past year and offer strong reason to consider surveillance, under appropriate circumstances, as an acceptable alternative to immediate biopsy for probably benign mammographically detected lesions. PMID- 1888656 TI - Mammography in younger women. AB - Breast imaging is not frequently performed in women aged 35 years or younger for several reasons. Approximately half of the radiographic examinations of a breast symptom give normal results because the expected density of the breast in younger women may obscure abnormalities. Results from biopsies performed subsequent to positive mammogram findings confirm the predominance of benign lesions; cancers are rarely observed. After reviewing the main breast diseases that occur in the 20- to 35-year-old age group, we evaluated the accuracy of mammography in diagnosing malignancy, and attempted to summarize guidelines for breast imaging in young women, whose breasts are quite sensitive to radiation. PMID- 1888657 TI - Cardiac imaging. PMID- 1888658 TI - Breast. PMID- 1888659 TI - Some remarks on the bias of the MPN method. AB - The estimation of cell number by using the MPN method was studied mathematically for three parallel inoculations from three decimal dilutions. As a result of computation it can be established that these estimations at a range of microbial numbers over 10 are biased. Confidential estimation could be obtained at cell numbers between 0 and 10 accepting only a few combinations of positive and negative test tubes. These are 1 0 0, 2 0 0, 3 0 0, 3 1 0 and 3 2 0. PMID- 1888660 TI - Growth of and toxin production by Aeromonas hydrophila and Aeromonas sobria at low temperatures. AB - The effects of different temperatures on the growth and toxin production of Aeromonas hydrophila and Aeromonas sobria were studied. The results showed that these Aeromonas species are not only able to grow at low temperatures (e.g. at 4 and 10 degrees C) but may also produce cytotoxin, hemolysin and enterotoxin under suitable growth conditions. PMID- 1888661 TI - The growth of salmonellae in tomatoes. AB - The growth of Salmonella enteritidis, S. infantis and S. typhimurium in tomatoes was studied at 7,22 and 30 degrees C. The pH values of tomatoes varied from 3.99 to 4.37 before incubation and from 3.90 to 4.36 after incubation at different temperatures. No growth was observed at 7 degrees C. S. enteritidis, S. infantis and S. typhimurium grew from cell densities of 1.2 x 10(1), 0.7 x 10(1) per g to 2.0 x 10(6), 2.3 x 10(6) and 7.1 x 10(6) per g, respectively, at 22 degrees C in 24 h. At 30 degrees C, the number of bacteria was about one logarithmic unit higher than at 22 degrees C after the same incubation time. The results of this study demonstrated a possible risk of tomatoes as vehicles of Salmonella spp. PMID- 1888662 TI - Increased production of oxygen free radicals in cigarette smokers. AB - Oxygen free radicals are known to produce damage in many biological tissues. Cigarette smoking is a major risk factor for various diseases. It is possible that oxygen free radical producing activity of polymorphonuclear (PMN) leucocytes is increased by cigarette smoking. We studied the oxygen free radical producing (luminol-dependent chemiluminescent) activity of PMN leucocytes in blood and the malondialdehyde (lipid peroxidation product) content of blood and serum in nonsmokers and smokers. The zymosan-induced chemiluminescent activity was measured on a LKB 1251 luminometer. The malondialdehyde (MDA) was measured as thiobarbituric acid (TBA) reactive substances. The chemiluminescent activity due to oxygen-derived free radicals (superoxide anion, hydrogen peroxide, hydroxyl radical) and superoxide dismutase (SOD)-inhibitable (superoxide anion) in nonsmokers were 1215.1 +/- 91.1 and 849.3 +/- 72.3 mV min/10(6) PMN leucocytes respectively. There was a significant increase in the oxygen-derived free radicals and SOD-inhibitable chemiluminescence in smokers. The values of blood and serum MDA were 171.7 +/- 6.1 and 222.2 +/- 5.6 nmoles/l respectively in nonsmokers. There was an increase in both blood and serum MDA in smokers. These results suggest that the increased generation of oxygen free radicals by PMN leucocytes might be responsible for an enhanced risk of various diseases related to cigarette smoking. PMID- 1888663 TI - Inhibition of the presentation of dengue virus antigen by macrophages to B cells by serine-protease inhibitors. AB - It has been shown that macrophages (M phi) process dengue type 2 virus (DV) antigen and present it to B cells leading to their clonal expansion as shown by DV-specific IgM antibody plaque-forming cell (PFC) count in spleen. The present study was undertaken to find out the nature of enzymes responsible for the processing of DV antigen in M phi. DV-pulsed M phi were treated with seven different protease inhibitors and then assayed for antigen presentation to B cells. It was observed that maximum inhibition occurred by treatment of M phi with PMSF, a serine-protease inhibitor. The effect of PMSF was dose dependent and was abolished by using predigested antigen. PMSF inhibited presentation of DV and sheep RBC antigens but had no effect on presentation of bovine serum albumin which does not require processing. The results thus identify the serine group of proteases as the main enzymes involved in processing the DV antigen in M phi. PMID- 1888664 TI - Effect of oral phytohaemagglutinin intake on cell adaptation in the epithelium of the small intestine of the rat. AB - The effect of phytohaemagglutinin (PHA) on the adaptation of the proximal jejunal epithelium and on the distal ileal epithelium was studied in rats. The group receiving PHA gained less weight than controls, and the enterocyte population of their jejunal villi, as well as the morphokinetic parameters (length, population, crypt cell production per crypt) of their jejunal and ileal crypts were higher than those of the controls. The proximal lesion caused by PHA (reduction of villus cell populations) stimulates hyperplasia of the crypt-villus unit of the ileal epithelium with the development of adaptation from afar. These adaptations occurred in animals that ingested PHA even in the presence of severe malnutrition. PMID- 1888665 TI - Acute histopathological changes produced by Penicillium aurantiogriseum nephrotoxin in the rat. AB - Shredded wheat moulded by an isolate of Penicillium aurantiogriseum elicited progressive histopathological changes at the rat renal cortico-medullary junction during 5 days of dosing, when incorporated into diet as a 20% component. The changes of acute tubular necrosis and regeneration were seen in the P3 segment of the nephron. In rats exposed to contaminated diet for 5 days the histopathological changes regressed in severity by about one-half within a further 4 days on normal diet and by 7 days the tubular epithelium was nearly normal. A partially purified fraction of an alcohol extract, selected by preparative high-voltage electrophoresis and anion exchange and notably rich in amino-compounds, was typically nephrotoxic when given in diet over 4 days. Acute marked tubular necrosis also occurred when the same fraction was given intraperitoneally over a similar period. The acute histological changes provide a rapid bioassay for this Penicillium nephrotoxicity and facilitate the search for the toxic metabolite(s). The cumulative expression of necrosis and repair over only a few days in tubular epithelium suggests that chronic exposure will elicit a more complex pathology which might serve as an experimental model for the idiopathic Balkan endemic nephropathy. PMID- 1888666 TI - Antigen-specific and non-specific depression of proliferative responses induced during contact sensitivity in mice. AB - Exposure of the flank of mice to either oxazolone or trinitrochlorobenzene (TNCB) 5 days prior to the application of oxazolone on the ear resulted in a reduced capacity of oxazolone-induced draining lymph node cells to express IL-2 receptors, produce IL-2, protein, RNA and DNA. However, histological examination of the draining lymph node suggest that antigen-specific and antigen-non-specific influences differ with respect to the frequency of pyroninophilic cells. Pre exposure to oxazolone suppressed the number of oxazolone-induced pyroninophilic T cell blasts, whereas draining lymph nodes from TNCB-pretreated mice contained significantly more pyroninophilic cells than from oxazolone-pretreated mice. However, the majority of these cells were incorporating little or no thymidine. Thus exposure to certain contact sensitizers induces at least two systemic control mechanisms which serve to regulate subsequent lymphoproliferative responses. These mechanisms appear to exert their influences at different stages of in-vivo T cell activation. PMID- 1888667 TI - The effects of some anti-arthritic drugs and cytokines on the shape and function of rodent macrophages. AB - Non-steroidal antiinflammatory drugs (NSAID) enhanced the spreading of mouse and rat peritoneal macrophages attached to either plastic or glass. This was probably due to drug inhibition of prostaglandin E2 (PGE2) production since spreading was also inhibited by adding exogenous PGE2. Corticosteroids (dexamethasone, cortisol and prednisolone) and some immunosuppressants (6-mercaptopurine, methotrexate, but not cyclosporin-A) also enhanced in-vitro spreading of murine peritoneal macrophages. Some recombinant cytokines (human tumour necrosis factor alpha and beta, murine tumour necrosis factor alpha, and murine interferon gamma, but not human interferon gamma) also enhanced the spreading of mouse peritoneal macrophages in vitro. Scanning electron microscopy revealed significant differences in morphology of cells induced to spread by these drugs and cytokines. NSAID treatment also enhanced macrophage clumping in vitro, indicating that cell spreading may play an important role in the resolution of inflammatory processes and/or the formation of multinucleated giant cells. PMID- 1888668 TI - The c-src family of protein-tyrosine kinases. PMID- 1888669 TI - Stereotaxic placement of a ventricular catheter and reservoir for the administration of morphine sulfate. AB - Patients with intractable pain due to cancer present a unique challenge to both medical and nursing personnel. This case study illustrates a unique home hospice managed pain control regime that has been implemented for a terminal cancer patient with intractable pain. A ventricular catheter attached to a reservoir was stereotaxically implanted for the administration of preservative-free morphine sulfate. The presentation will include the history of intraspinal morphine, the surgical placement of the ventricular access devise, and the procedure for intraventricular morphine administration. Also, the preoperative nursing assessment and patient family education will be discussed. Education of hospice nurses in the technique of injection, postoperative pain assessment, monitoring of side effects and discharge planning will conclude the presentation. PMID- 1888670 TI - Effects of multiple sclerosis on occupational and career patterns. AB - The paper will examine the impact of multiple sclerosis on occupational roles and career patterns of 210 persons registered with the Vancouver Island Multiple Sclerosis Society. METHODOLOGY: 210 participants responded to a 17-item mailed questionnaire. Items pertained to participants' demographic characteristics, medical history related to MS, years of career training, occupational history and changes in employment associated with changes in physical status due to MS. FINDINGS: An initial analysis indicates that the majority of the respondents (64.8%) were 30-59 years of age, the years of greatest career development. Although 97.1% of respondents had held a job at some time in their lives, only 24% were employed on a full or part-time basis at the time of the study. The greatest decrease in employment occurred in health related professions and service industries. Disabilities and symptoms which had the greatest effect on employment were fatigue and muscle weakness. Identified work related problems included inability to work full time and inaccessible environments. The paper will discuss strategies nurses can use to assist employees with MS. PMID- 1888671 TI - The pain experience of a multiple sclerosis population: a descriptive study. AB - A detailed survey questionnaire was distributed to patients attending a multiple sclerosis clinic for the purpose of describing the pain experience of an MS population. Three hundred and sixty-four (364) questionnaires were completed and returned for evaluation. Two hundred and thirty-three (233) or 64 percent of subjects surveyed reported painful symptoms at some time during the course of their disease. Data was gathered and analyzed with regard to age, gender, duration of illness, age of onset of MS, employment status, classification of disease, onset of painful symptoms and their frequency and intensity. Similarities between the two groups (pain vs no pain) were observed in mean age (44.15 years vs 43.40), duration of illness (10.97 years vs 10.26 years), employment status (56 percent employed vs 57 percent employed), age of disease onset (33.74 years vs 32.07 years) and breakdown of illness classifications in both groups. Onset of pain was reported at time of diagnosis or before in 41 percent of subjects surveyed. Females were more likely to complain of pain than were men (68 percent vs 55 percent) and tended to report a significantly higher pain intensity than males. Forty-nine percent of subjects with pain reported difficulty working, 44 percent difficulty sleeping and 34 percent reported troubled interpersonal relationships. Forty percent of patients with pain report never being completely pain free. PMID- 1888672 TI - Stereochemical complementarity of progesterone and cavities between base pairs in partially unwound double stranded DNA using computer modeling and energy calculations to determine degree of fit. AB - Computer modeling was applied for the first time to investigate previously reported complementarity of progesterone and cavities formed between base pairs in partially unwound double stranded DNA. Computer graphics enabled a more objective assessment of complementarity; energy calculations provided a rigorous method to evaluate degree of fit. Graphics confirmed that the complementarity was virtually "lock and key", i.e. close contacts were formed between van der Waals surfaces in the progesterone/DNA complexes and hydrogen bonds were formed between the two carbonyl groups on opposite ends of the steroid and phosphate groups on adjacent strands of DNA. Molecular mechanics calculations revealed that insertion of the steroid resulted in a relatively stable complex i.e. both van der Waals and electrostatic energies were lowered due to favorable steric interactions and stereospecific hydrogen bonds, respectively. Three published X-ray crystal structures of progesterone exhibited similar complementarity. Ent-progesterone which does not occur naturally possessed very poor complementarity. These findings confirm that the structure of progesterone is directly reflected in the stereochemistry of DNA. While no mechanistic explanation for these results is proffered, we hypothesize that such complementarity must have played a decisive role in the evolution of steroid hormone structure and function. PMID- 1888673 TI - Corticosterone regulation of brain and lymphoid corticosteroid receptors. AB - Circulating lymphocytes are often used as a model for brain corticosteroid receptor regulation in clinical disease states, although it is not known if lymphoid receptors are regulated in a similar manner as brain receptors. In the present study the regulation of brain (hippocampus, frontal cortex, hypothalamus and striatum), lymphoid (circulating lymphocytes, spleen and thymus) and pituitary glucocorticoid receptors in response to alterations in circulating corticosterone levels was examined. Seven days following adrenalectomy, type II corticosteroid receptors (i.e. glucocorticoid receptors) were significantly increased in the hippocampus, frontal cortex and hypothalamus, but not in any other tissues. Administration of corticosterone (10 mg/kg) for 7 days significantly decreased type II as well as type I (i.e. mineralocorticoid receptors) receptors in the hippocampus. Type II receptors in the frontal cortex, circulating lymphocytes and spleen were also significantly decreased by chronic corticosterone treatment. Immobilization stress (2 h a day for 5 days) failed to alter receptor density in any of the tissues. These results demonstrate that homologous regulation of corticosteroid receptors by corticosterone does not invariably occur in all tissues and emphasize the complex degree of regulation of these receptors. However, the simultaneous downregulation of both hippocampal and lymphocyte glucocorticoid receptors by corticosterone provides support for the hypothesis that circulating lymphocytes do reflect some aspects of brain glucocorticoid receptor regulation. PMID- 1888674 TI - Effects of orchidectomy and different modes of high dose estrogen treatment on circulating "free" and total 1,25-dihydroxyvitamin D in patients with prostatic cancer. AB - Serum levels of total 1,25-dihydroxyvitamin D (1,25(OH)2D), vitamin D binding protein (DBP), sex hormone binding globulin (SHBG), testosterone, estradiol 17 beta (E2) and the "free" 1,25(OH)2D index were measured before and during treatment in prostatic cancer patients treated by orchidectomy (n = 15), with combined i.m. polyestradiol phosphate (PEP) + oral ethinyl estradiol (EE) (n = 10) and with i.m. PEP only for 3 months, followed by addition of oral EE (n = 9). Total concentrations of 1,25(OH)2D and DBP were unaffected by orchidectomy and treatment with i.m. PEP only, but were significantly elevated during treatment including oral EE. SHBG levels were unaffected by orchidectomy, slightly increased by i.m. PEP only and greatly increased by oral EE. The free 1,25(OH)2D index was slightly elevated by treatment including oral EE. Evidence was obtained that the increase in 1,25(OH)2D levels observed during oral estrogen treatment was secondary to the estrogen-augmented increase in DBP and not a result of an estrogen-stimulated synthesis of 1,25(OH)2D. Furthermore, the stimulatory effect of estrogen on DBP concentrations seemed to be dependent on the route of administration of the hormone. PMID- 1888675 TI - Inhibitory effects of gossypol on corticosteroid 11-beta-hydroxysteroid dehydrogenase from guinea pig kidney: a possible mechanism for causing hypokalemia. AB - Inhibition of 11-beta-hydroxysteroid dehydrogenase (11-beta-OHSD) in the kidney can cause excess mineralocorticoid effect and hypokalemia. To find out if gossypol, a potential oral contraceptive for men that has been associated with cases of hypokalemia, inhibits this enzyme, its effect on guinea pig kidney was studied. Working with microsomes from the kidney cortex, and using corticosterone as the substrate, racemic gossypol was found to be a competitive inhibitor of 11 beta-OHSD with a Ki of 67 +/- 5 microM. The (+) enantiomer was a little more potent than the (-) enantiomer. Microsomes from the kidneys of animals given gossypol for 2 weeks had lower enzyme activities than saline-treated animals. Microsomes from a strain of hairless guinea pigs had lower intrinsic enzyme activity than the normal animals. We conclude that there is genetic variation in the activity of this enzyme and that it can be inhibited by gossypol. PMID- 1888676 TI - Steroid determinations in human ovarian follicular fluid using reversed phase liquid chromatography. AB - A method is presented, based on high performance liquid chromatography (HPLC) with u.v. absorbance detection, to simultaneously analyse all major unconjugated steroids in ovarian follicular fluids. The total analysis time is only 30 min. The use of a 3 mm i.d. column allows us to obtain detection limits for 3-oxo-4 ene steroids of 2 ng/ml. Calibration curves are linear in the 10-20,000 ng range per injection. Excellent agreement is obtained with the results using a previously published gaschromatography method. PMID- 1888677 TI - The effect of gonadectomy and aromatase inhibition on the excretion of 19 nordeoxycorticosterone in rats. AB - 19-Nordeoxycorticosterone (19-norDOC) is a powerful mineralocorticoid, which has been postulated to be involved in the pathogenesis of some forms of hypertension. The urinary excretion of 19-norDOC by female rats is up to 20 times that of males. To demonstrate the influence of the gonads on the excretion of 19-norDOC, we measured the excretion of 19-norDOC in intact and gonadectomized male and female rats with and without replacement with testosterone (40 mg testosterone enanthate s.c.) or estrogen (4 mg estradiol valerate s.c.) and in intact animals receiving the aromatase inhibitor, 10-propargyl androstenedione (10-pA) (10 mg s.c.). Orchiectomy produced a significant increase in the urinary excretion of 19 norDOC in males. Testosterone treatment decreased 19-norDOC excretion by castrated males to below intact values, while estrogen administration increased its excretion. Oophorectomy had no consistent effect on 19-norDOC excretion. In oophorectomized females, testosterone administration significantly suppressed 19 norDOC excretion and estrogen replacement increased excretion slightly. 10-pA had little effect on the excretion of 19-norDOC in intact rats of either sex. In conclusion, it appears that 19-norDOC production is inhibited by testosterone, but is affected only slightly by estrogens. PMID- 1888678 TI - Direct time-resolved fluoroimmunoassay of estriol in serum. AB - A rapid, direct, solid-phase, time-resolved fluoroimmunoassay for free estriol in serum, using Europium-chelate-protein A as a label, is described. The coefficient of correlation with the results of RIA was 0.983. PMID- 1888679 TI - Induction of progestin receptors in the mediobasal hypothalamus of gonadally intact male rats primed with estrogen in relation to display of lordosis behavior. AB - The purpose of this study was to determine whether the effects of estrogen on lordosis behavior in the male rat were related to the number of progesterone (P) receptors in the mediobasal hypothalamus (MBH) and/or dependent on blood P concentration. Two groups of gonadally intact male rats were given five successive doses of 1.0 or 2.5 micrograms estradiol benzoate (EB) and tested for lordosis behavior with a male stimulus at the end of the treatment. One month later they were again injected with EB and sacrificed under the same temporal schedule, but they were not tested for lordosis so as to prevent any emotionally stressful effects of intermale cohabitation. The males given 2.5 micrograms EB more frequently displayed lordosis responses to male mounts than those receiving 1 microgram EB, with a parallel increase in the number of MBH P receptors. The total number of MBH P receptors also appeared to be higher in the animals that displayed lordosis responses (lordosis group) than in those which did not (no lordosis group). In contrast, the display of lordosis behavior was negatively correlated with blood P concentration. Comparing MBH P receptors and blood P values in the EB treated and in nonhormonally treated gonadally intact animals which had been selected for either ability or inability to spontaneously display lordosis behavior, we observed that (1) EB was capable of increasing the number of MBH P receptors in the male rat; and (2) in the absence of EB treatment blood P values were higher in the animals showing lordosis than in those which did not. These data are discussed with respect to observations made in castrated male rats and in ovariectomized females. PMID- 1888680 TI - Metabolism of E1 and E2 in Ishikawa endometrium carcinoma cells: influence of TNF alpha. AB - The metabolism of estrone (E1) and estradiol (E2) by Ishikawa endometrial carcinoma cells and its alteration by TNF alpha treatment was studied. Whereas this cell line practically does not respond to estrogens, it is very sensitive to TNF with respect to growth inhibition and other parameters. E2 and E1 were found to be metabolized by this cell line whereby the main metabolite for both estrogens was estriol. TNF significantly increased the rate of E1 and E2 conversion. PMID- 1888681 TI - Steroid hormones as mediators of neural plasticity. AB - Steroid and thyroid hormone receptors are expressed in the developing brain and persist throughout adult life. They mediate a variety of effects on the brain, ranging from developmental effects of thyroid hormone and the process of sexual differentiation to the cyclic changes during reproductive cycles in adult female animals. This review summarizes data from the author's laboratory on three topics: (1) actions of extradiol and progesterone on the ventromedial nucleus of the hypothalamus in adult female and male rats, showing both the cyclicity and the consequences of brain sexual differentiation; (2) actions of estradiol on the cholinergic neurons of the basal forebrain of the female and male rat, reflecting the plasticity of the adult cholinergic system as well as sex differences which are developmentally programmed; and (3) diverse actions of estrogens, thyroid hormone and glucocorticoids on the morphology of hippocampal neurons. The review concludes by discussing the interactions between "organizational" (i.e. developmental) effects and the "activational" effects of steroids on the mature nervous system in relation to the environmental control of brain gene expression. PMID- 1888682 TI - Symposium on psychoendocrinology in honour of Professor Marion Krantz Birmingham. Montreal, Canada, 11 November 1989. PMID- 1888683 TI - Regulation of glucocorticoid receptors in human mononuclear cells: effects of glucocorticoid treatment, Cushing's disease and ketoconazole. AB - Glucocorticoid receptors (GcR) were determined by a whole cell assay in human mononulear leukocytes (hMNL) from control subjects, patients receiving glucocorticoid therapy for systemic diseases and Cushing's disease patients with or without ketoconazole therapy. Prolonged corticosteroid treatment resulted in down-regulation of GcR, while the mean level of GcR in Cushing's disease was normal. In this group, however, receptor levels and morning plasma cortisol values showed a negative correlation, indicating a subtle down-regulatory effect. Furthermore, GcR were unaltered after these patients received ketoconazole, in spite of a marked reduction in morning plasma cortisol and urinary free cortisol. We also observed that ketoconazole was a weak competitor of GcR in intact cells, although it significantly inhibited [3H] dexamethasone binding in cytosolic preparations from rat tissues. The results suggested that GcR in hMNL are down regulated by synthetic steroids given in vivo, but they showed very mild down regulation in hypercortisolemic patients suffering from Cushing's disease. Finally, we did not observed either up-regulation or antagonism of GcR by ketoconazole treatment, at the time that cortisol levels of patients with Cushing's disease were reduced. This indicates that the beneficial effects of ketoconazole in Cushing's disease are due to adrenal cortisol suppression and not to interaction with GcR of target cells, and that the process of GcR regulation in hMNL is a complex phenomenon awaiting further elucidation. PMID- 1888684 TI - Treatment of major depression with steroid suppressive drugs. AB - The hypercorticism frequently observed in major depression, unaccompanied by signs of Cushing's syndrome, is still poorly understood. One suicidal young woman, with very high cortisol levels and unusual resistance to dexamethasone suppression, is described. She was successfully treated with steroid suppressive drugs (aminoglutethimide, metyrapone), had a prompt and complete remission and has remained well for more than two years on no medication. This success prompted an on-going clinical trial of this therapy. The available drugs and a working hypothesis of their action are discussed. PMID- 1888685 TI - Modulation by adrenal steroids of limbic function. AB - The effects of various steroid hormones on the long-term potentiation (LTP) of the rat hippocampus were evaluated. LTP was elicited in the dentate gyrus of adrenalectomized animals with priming tetanic stimulation (200 Hz-0.03 cps) of its main afferent, the perforant pathway. Single pulse EPSP (excitatory post synaptic potential) slope, and PS (population spike) amplitude values were compared before and after the i.v. injection of the hormones and subsequently after the priming stimulation every 15 min up to 1 h. 18-OH-deoxycorticosterone (18-OH-DOC) produced a significant decrease of the EPSP LTP and arrested the PS enhancement in comparison with vehicle at every time post-tetanic stimulation. Its 21-acetate derivative produced a moderate decrease of the EPSP and had no effect on the PS LTP in comparison with vehicle. Deoxycorticosterone (DOC) exhibited similar effects on the EPSP although less marked than with 18-OH-DOC while the PS only decreased in the first 30 min post-train. Corticosterone decreased both EPSP and PS for the first 15 and 30 min after priming stimulation, respectively, matching values with those of vehicle afterwards. Its 21-acetate produced an initial decrease of the EPSP and had no effect on the PS LTP. Allo tetrahydro-DOC produced little, if any, initial enhancement of the PS LTP in comparison with vehicle. These results show that the adrenal steroids tested can modulate hippocampal LTP, a plastic phenomenon in the mammalian CNS which is known to be related to memory and learning processes. Moreover, adrenal steroids can independently modify the PS or EPSP components of the LTP, suggesting different loci of action at the neuronal level. PMID- 1888686 TI - Regulatory effects of 5 beta-reduced steroids. AB - The first section of this publication summarizes early work according to which 5 beta-pregnanedione is an important metabolite of progesterone in the early stages of the chick embryo's adrenal steroidogenesis, then decreasing gradually as corticosteroidogenesis increases. In the second section a model is described in which adrenal 3 beta-ol hydroxylase-isomerase of the 17-day-old chicken is suppressed pharmacologically, this suppression being correlated with that of the synthesis of aminoevulinic acid (ALA), the first and rate-limiting step of the heme pathway. 5 beta-Pregnanedione (10(-7)-10(-6) M) restored ALA synthesis in this inhibited model to normal values. The effect of 5 beta-pregnanedione was specific since other steroids tested: progesterone; 5 alpha-pregnanedione; corticosterone or estradiol, did not stimulate ALA. Since heme formation by steroidogenic glands contributes to the synthesis of cytochrome P450 rather than hemoglobin, 5 beta-pregnanedione was also assayed as a stimulator of this enzyme system and was found to increase cytochrome P450 in adrenals and testes but not in the liver. In view of these results a hypothesis is advanced according to which 5 beta-reduced progestagens and androgens stimulate cytochrome P450 formation, i.e. the synthesis of progesterone and higher hydroxylated steroids, by steroidogenic glands in the event of an excessive precursor reduction. PMID- 1888687 TI - Cellular mechanisms underlying the development and expression of individual differences in the hypothalamic-pituitary-adrenal stress response. AB - Several years ago Levine, Denenberg, Ader, and others described the effects of postnatal "handling" on the development of behavioral and endocrine responses to stress. As adults, handled rats exhibited attenuated fearfulness in novel environments and a less pronounced increase in the secretion of the adrenal glucocorticoids in response to a variety of stressors. These findings clearly demonstrated that the development of rudimentary, adaptive responses to stress could be modified by environmental events. We have followed these earlier studies, convinced that this paradigm provides a marvellous opportunity to examine how subtle variations in the early environment alter the development of specific neurochemical systems, leading to stable individual differences in biological responses to stimuli that threaten homeostasis. In this work we have shown how early handling influences the development of certain brain regions that regulate glucocorticoid negative-feedback inhibition over hypothalamic-pituitary adrenal (HPA) activity. Specifically, handling increases glucocorticoid (type II corticosteroid) receptor density in the hippocampus and frontal cortex, enhancing the sensitivity of these structures to the negative-feedback effects of elevated circulating glucocorticoids, and increasing the efficacy of neural inhibition over ACTH secretion. These effects are reflected in the differential secretory pattern of ACTH and corticosterone in handled and nonhandled animals under conditions of stress. In more recent years, using a hippocampal cell culture system, we have provided evidence for the importance of serotonin-induced changes in cAMP levels in mediating the effect of postnatal handling on hippocampal glucocorticoid receptor density. The results of these studies are consistent with the idea that environmental events in early life can permanently alter glucocorticoid receptor gene expression in the hippocampus, providing evidence for a neural mechanism for the development of individual differences in HPA function. PMID- 1888688 TI - The premenstrual syndrome and its treatment. AB - The premenstrual syndrome has been described briefly and the literature relating to its pathophysiology and treatment have been reviewed. The great number of theories as to etiology and many different kinds of treatments attest to our ignorance of the exact nature of this problem. Although it is obvious that the hypothalamo-pituitary-ovarian axis must be involved, the exact mechanism whereby the symptoms come about remains elusive. Progestin in the presence of estrogen appears to be essential. Excess estrogen may aggravate the condition. The popular theory of progesterone deficiency has not been supported by double blind trials of progesterone in various forms versus placebo. Because of the important placebo effect in this condition, double blind trials are essential in the assessment of any form of treatment. PMID- 1888689 TI - The steroid hormone of sunlight soltriol (vitamin D) as a seasonal regulator of biological activities and photoperiodic rhythms. AB - Neural and systemic somatotrophic effects of the ultraviolet component of sunlight through the skin-vitamin D endocrine system are considered as alternate or additional to the neuroendocrine effects of the visual component of light through the retino-diencephalic input. The extensive distribution of soltriol nuclear receptor cells, revealed by autoradiography with tritium-labeled 1,25 dihydroxycholecalciferol (vitamin D, soltriol) and related effects, indicate an involvement of vitamin D-soltriol in the actinic induction of seasonal biorhythms. This is considered to be independent of the traditionally assigned effects of vitamin D on systemic calcium regulation. Skin-soltriol mediated seasonal, and to a degree daily, genomic activation involves many target regions in the brain. These include neurons in the central nucleus of the amygdala, in the linked part of the bed nucleus of the stria terminalis, in periventricular hypothalamic neurons, dorsal raphe nucleus, reticular thalamic nucleus and autonomic, endocrine as well as sensory and motor components of the brainstem and spinal cord. Additional to the eye-regulated "suprachiasmatic clock", existence of a soltriol-vitamin D regulated neural "timing circuit(s)" is proposed. Both, activational and organizational effects of soltriol on mature and developing brain regions, respectively are likely to play a role in the regulation of neuronal functions that include the modulation and entrainment of biorhythms. Soltriol's central effects correlate with peripheral effects on elements in skin, bone, teeth, kidney, intestine, heart and blood vessels, endocrine organs, and tissues of the immune and reproductive system. PMID- 1888690 TI - Calcium antagonists and myocardial infarction. AB - In vitro and in vivo studies have demonstrated many similarities between the three calcium antagonists verapamil, nifedipine, and diltiazem in relation to protection of the myocardium during hypoxia. Important clinical differences exist between the three drugs when they are used during or after an acute myocardial infarction with the purpose of preventing death and reinfarction. The balance between the negative inotropic and the vasodilator properties and concomitant treatment with beta blockers may explain the results of clinical trials with the three calcium antagonists. Patients not treated with beta blockers. Nifedipine has been demonstrated to be no better than placebo both during and after an acute myocardial infarction. No placebo-controlled studies exist with diltiazem. Verapamil had no effect during the acute phase of a myocardial infarction. After a myocardial infarction, verapamil improved survival and reduced the reinfarction rate, an effect primarily found in patients without heart failure in the coronary care unit. Patients also treated with beta blockers. Nifedipine prevents the development of myocardial infarcts in patients with unstable angina. Diltiazem probably prevents reinfarction in the first two weeks after non-Q-wave infarction. Secondary prevention with diltiazem after an acute myocardial infarction had no overall effect on death or cardiac events (i.e., reinfarction or cardiac death). Subgroup analysis demonstrated in diltiazem-treated patients, compared with placebo-treated patients, a significant reduction of cardiac events in patients without and a significant increase of cardiac events in patients with heart failure. At present no indications exist for nifedipine during or after a myocardial infarction; further studies are needed with diltiazem, and verapamil may be used in secondary prevention of death and reinfarction. PMID- 1888691 TI - Magnesium content of erythrocytes in patients with vasospastic angina. AB - The possibility that a magnesium deficiency might be the underlying cause of vasospastic angina (VA) and the efficacy of Mg administration in its treatment were studied. Subjects included 15 patients with VA and 18 healthy subjects as the control group. The erythrocyte Mg content was measured by atomic absorption, and serum Mg was measured by conventional chemical assay. The efficacy of Mg administration was studied in seven patients with VA. The results were as follows: a) The mean erythrocyte Mg content was less in the group with frequent episodes of angina (1.59 +/- 0.11 mg/dl) than in the group without angina (2.11 +/- 0.38 mg/dl, p less than 0.01) and in the control group (2.22 +/- 0.29 mg/dl, p less than 0.01). There was no significant difference between the control group and patients of each group with respect to serum Mg. b) Coronary arterial spasm was induced by ergonovine maleate in seven patients and was completely inhibited by the administration of Mg sulfate (40-80 mEq, hourly) in six of these patients; in the remaining patient neither obvious ST change nor chest pain occurred. Thus, it was concluded that the measurement of erythrocyte Mg content is useful to determine how easily vasospasm might occur in VA and that the administration of Mg might be developed as a new therapy for spasm associated with a low erythrocyte Mg content. PMID- 1888692 TI - Effect of the acute sublingual administration of ketanserin in hypertensive patients. AB - The purpose of this study has been to compare the acute antihypertensive effect of a dose of 20 mg of ketanserin in 18 patients after sublingual administration and in 19 after oral administration. In three patients ketanserin and ketanserin ol plasma levels were measured after both sublingual and oral administration. The results showed a more rapid, considerable antihypertensive effect after sublingual administration. In addition, the high plasma levels of ketanserin-ol, the metabolite produced by hepatic reduction of ketanserin, reached after sublingual administration, rather than transmucosal absorption, indicate that the clinical effect observed is due to more rapid dissolution of the tablet formulation and liberation of the active drug. PMID- 1888693 TI - Twenty-four hour ambulatory blood pressure profile of a new slow-release formulation of diltiazem in mild to moderate hypertension. AB - Twelve patients with a mild to moderate essential hypertension were included in a double-blind, balanced, randomized placebo-controlled cross-over study to assess the efficacy and duration of action of a new slow-release formulation of diltiazem (300 mg) given once daily for 3 weeks. All office blood pressure measurements were done 24 hours after drug intake. In order to improve the accuracy of the trial, 24-hours non-invasive ambulatory blood pressure monitoring (Spacelabs 90207 system) were performed as well. Diltiazem significantly lowered supine and standing systolic and diastolic office blood pressure (by 16.9/12.7 mmHg and by 17.3/13.8 mmHg, respectively), without changing office heart rate. Diltiazem also significantly lowered ambulatory blood pressure measured over 24 hours, as well as ambulatory heart rate. The blood pressure lowering effect was most pronounced during the daytime period and did not reach statistical significance during the sleeping hours. The treatment was well tolerated, and there were no significant side effects. The results confirm the antihypertensive efficacy of diltiazem LP 300 mg once daily during the daytime and during the early morning blood pressure rise, without inducing nocturnal hypotension. PMID- 1888694 TI - Amiloride improves hemodynamics in patients with chronic congestive heart failure treated with chronic digoxin and diuretics. AB - Potassium-sparing diuretics have been reported to decrease the positive inotropic effect of digoxin. We studied the hemodynamic effects of amiloride in patients taking digoxin for chronic heart failure. Eleven men with a history of congestive heart failure were studied in a double blind, cross-over, placebo controlled trial with the patients on digoxin alternating placebo with amiloride. After 7 days on the trial drug, a Swan-Ganz catheter was placed in the pulmonary artery and measurements made at rest and with increasing degrees of supine bicycle exercise. Right-sided and pulmonary artery wedge pressures and systemic arterial pressures, as well as cardiac outputs, were measured. After a 7 day washout period, placebo (P) and Amiloride (A) were switched and after 7 days on the therapy, a second hemodynamic study at rest and varying degrees of supine bicycle exercise was repeated. At rest there were no significant differences in the right sided, pulmonary arterial wedge pressure or cardiac outputs between the patients on Amiloride (A) versus placebo (P). During exercise there were significant differences between (P) and (A) at the 50 watt-second stage of exercise.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1888695 TI - Effects of the angiotensin converting enzyme inhibitor, benazepril, on the sino aortic baroreceptor heart rate reflex. AB - The effects of monotherapy with the angiotensin converting enzyme inhibitor benazepril (10 mg once daily) on cardiovascular baroreceptor reflexes were determined in 10 patients with essential hypertension using a randomized, double blind, placebo-controlled, cross-over protocol. Early sino-aortic baroreceptor/heart rate reflex resetting was apparent with acute treatment; this effect persisted throughout the active treatment period. Changes in baroreflex sensitivity did not appear to mediate the hypotensive effect of benazepril. PMID- 1888697 TI - Positive and negative factors regulate the transcription of the ETS2 gene via an oncogene-responsive-like unit within the ETS2 promoter region. AB - The DNA-protein interactions in the ETS2 promoter have been studied. Three distinct sequence motifs have been identified, each of which interacts with at least two distinctive protein complexes. The GC motif, possessing mirror symmetry, interacts with two ubiquitously identifiable complexes (S and S2); the PEA3 motif interacts with a ubiquitous (H1) and a tissue-specific (H3) complex; the H2 (an AP1-like) motif interacts also with a ubiquitous (H2a) and a tissue specific (H2b) complex. Mutational analysis and correlation of the presence of defined complexes with the ETS2 mRNA levels indicate that the S, S2, H1, and H2b complexes have positive effects on ETS2 transcription, whereas the H3 and H2a have negative effects. The organization of the PEA3 with the AP1-like motif in the ETS2 promoter resembles the oncogene-responsive unit previously identified in the polyoma virus enhancer region. Our data suggest that cooperation between these two motifs is vital for ETS2 promoter function. PMID- 1888696 TI - Effect of palmitic acid and fatty acid binding protein on ventricular fibrillation threshold in the perfused rat heart. AB - The effects of increased free fatty acid (FFA) levels on ventricular arrhythmias remain controversial. Using ventricular fibrillation threshold (VFT), we examined the relationship between FFA levels and ventricular arrhythmias. Isolated rat hearts were perfused with palmitate bound to either albumin or fatty acid binding protein (FABP) by Langendorf's method. The VFT was determined by electrical stimulation. Perfusion with 0.12 mM albumin alone, 0.12 mM palmitate bound to 0.12 mM albumin, and 0.36 mM palmitate bound to 0.12 mM albumin did not lower the VFT significantly. However, 0.60 mM palmitate bound to 0.12 mM albumin lowered VFT from 2.19 +/- 0.20 mA to 1.56 +/- 0.13 mA. The perfusion of 0.36 mM palmitate bound to 0.12 mM FABP lowered the VFT from 2.05 +/- to 0.19 mA to 1.47 +/- 0.23 mA, but 0.12 mM FABP alone did not affect the VFT. Perfusion with 0.36 mM palmitate bound to 0.12 mM FABP caused the VFT to fall more than perfusion with 0.36 mM palmitate bound to 0.12 mM albumin. Then the effects of verapamil perfusion or a low concentration of perfusate Ca2+ on VFT were examined. VFT was determined by electrical stimulation. Palmitate (0.6 mM) bound to 0.12 mM albumin lowered VFT. Verapamil 10(-7) M perfusion and a low concentration of Ca2+ (Ca2+ 1.67 mM) suppressed the FFA-induced fall of VFT. These results suggested that the arrhythmogenic action of FFA was related to Ca2+ overload in myocardial cells. PMID- 1888698 TI - Structure, mapping, and expression of fisp-12, a growth factor-inducible gene encoding a secreted cysteine-rich protein. AB - We have characterized a growth factor-inducible gene, fisp-12, previously isolated by differential screening of a lambda complementary DNA library of RNA from serum-stimulated NIH 3T3 cells, and have shown that it encodes a cysteine rich secreted protein of 348 amino acids. The induction of fisp-12 mRNA is rapid and remains for at least 8 h at a high level of expression. The increased level of fisp-12 mRNA following serum stimulation is mainly due to transcriptional activation. Studies on the genomic structure reveal that the fisp-12 transcription unit is 3.1 kilobases long and split into five exons. The 5' flanking region does not contain serum-responsive elements normally found in other immediate early genes. Immunoprecipitation analyses show that the protein is rapidly induced following serum stimulation and that it is efficiently secreted in an unglycosylated form to the medium. The fisp-12 gene maps to the [10A3-10B1] region of the murine genome. PMID- 1888700 TI - [Recent advances in gene therapy and future prospects]. AB - Gene therapy, which is treatment of diseases by introducing normal genes into the body, is becoming feasible as the result of advances in genetic engineering. The hematopoietic stem cells have been considered as the appropriate target for gene transfer in many genetic diseases for which allogeneic bone marrow transplantation has been employed successfully. However, there are still many problems to be solved. In particular, expression from retrovirally transduced genes in bone marrow cells has been transient and unstable. On the other hand, an alternative approach to somatic cell gene therapy using nonhematopoietic cells, including skin fibroblasts, endothelial cells, keratinocytes, and lymphocytes, has been shown to possess several advantages. This kind of approach is usually applied to supplementation therapy in not only hereditary disorders but also various acquired diseases, such as cancer or infectious diseases. Recently, clinical application of gene transfer into lymphocytes to treat cancer and immunodeficiency have been approved at NIH (USA). The trial could represent the start of a new era in molecular medicine. PMID- 1888699 TI - Differential regulation of the p72-74 RAF-1 kinase in 3T3 fibroblasts expressing ras or src oncogenes. AB - The c-raf-1 protooncogene encodes a p72-74 serine/threonine-specific kinase that has been implicated in growth factor-mediated signal transduction and malignant transformation. Here, we compared the effects of Ha-c-ras and v-src oncogenes on the regulation of p72-74 RAF-1 kinase in NIH3T3 cells. In both serum-starved and platelet-derived growth factor-treated v-src-transformed cells, the RAF-1 kinase was constitutively activated, displaying characteristic retarded mobility in electrophoretic gels and elevated activity in in vitro kinase assays. In contrast, the RAF-1 protein from quiescent ras-transformed cells did not exhibit constitutively shifted gel mobility or elevated kinase activity but did respond normally with regard to platelet-derived growth factor- and phorbol myristate acetate-induced changes in p72-74 RAF-1 phosphorylation and kinase activity. 3T3 cells transformed by ras, however, contained elevated levels of p72-74 RAF-1 protein (as determined by immunoblotting), suggesting an indirect influence on this kinase. Quantitative differences in the levels and subcellular distribution of immunodetectable protein kinase C enzymes did not account for the differences between src- and ras-transformed 3T3 cells with regard to regulation of the RAF kinase. These findings in serum-deprived 3T3 cells demonstrate that expression of a ras oncogene can be insufficient for full activation of the p72-74 RAF-1 kinase, implying necessity for an additional growth factor-mediated stimulus. PMID- 1888701 TI - [Gene-transfer into bone marrow cells]. AB - We have intended to improve gene-transfer technique into hematopoietic stem cells for somatic gene therapy. 1) We have developed a new packaging cell line, ampGPE for retroviral production. LTR-less gag, pol or env genes from Moloney murine leukemia virus were separately inserted into BMGNeo vector. Packaging cell lines containing 20-50 copies of these two kinds of plasmid were obtained. Retrovirus stock for gene-transfer have been produced at a high titer (10(5)-10(6) cfu/ml) and without replication-competent viruses by using ampGPE. 2) Retrovirus transduced murine CFU-GM have been found to selectively proliferate (5-10 fold/week) in liquid capture with recombinant murine IL-3, human IL-6 and G418 to consequently obtain enough amount of, highly concentrated (70-100%), and gene transferred murine CFU-GM for gene-delivery system. PMID- 1888702 TI - [Resistance to anticancer drugs in NIH3T3 cells transfected with c-myc and/or c-H ras genes]. AB - NIH3T3 cells transfected with c-H-ras and/or c-myc genes were examined for differences in drug sensitivity. The two transfectants used were NIH3T3-nm-1 (nm 1), pT22-3-nm-2. They were transfected with c-myc, c-myc plus activated c-H-ras, respectively. The relative resistances (IC50 values of transfectants/those of NIH3T3 cells) to cisplatin, adriamycin, 4-hydroperoxycyclophosphamide, melphalan, and CPT-11 were 2.1, 1.6, 4.7, 4.9, 1.6, respectively for nm-1 and 1.6, 2.2, 3.3, 9.1 and 2.2, respectively for nm-2. These results strongly suggest that the expression of the c-myc gene plays a role for the acquisition of drug resistance. The c-myc gene is believed to provide us an important clue for determining the mechanism of drug resistance. PMID- 1888703 TI - [Identification of a chromosome carrying a putative tumor suppressor gene in human choriocarcinoma by microcell-mediated chromosome transfer]. AB - There are two main mechanisms of origin for complete hydatidiform mole; a) fertilization of an empty egg by a haploid sperm followed by duplication, and b) fertilization of such an egg by two haploid spermatozoa. It is widely accepted that, of all forms of pregnancy that had to choriocarcinoma, the risk associated with moles is by far the highest. Homozygous expression of a recessive mutation of moles has been assumed to associate with this propensity to malignancies. Alterations of several tumor suppressor genes together with activation of oncogenes are assumed to be necessary for choriocarcinogenesis. Genetic characteristics shown in the moles suggest that the former alterations are especially important to explore the multistep conversions to malignancies. Thus, individual chromosomes derived from normal cells were introduced into choriocarcinoma cells via microcell fusion. Evaluation of tumorigenicity in microcell hybrids suggested that chromosome #7 carried a putative tumor suppressor gene for choriocarcinoma. The gene imprinting or recessive mutation may be responsible for the inactivation of such a gene, being able to correspond with the high propensity to malignancy of moles. PMID- 1888704 TI - [Establishment and characterization of a human ureteral cancer cell line producing carbohydrate antigen 19-9 and carcinoembryonic antigen]. AB - We established a new cell line (FU-UrC-1) derived from a human primary ureteral carcinoma xenografted in a nude mouse. This cell line exhibited epithelial characteristics and formed clusters in monolayer cultures. The cells were subcultured in vitro for more than 20 passages and had a doubling time of 53 hours. The modal number of chromosomes was 66. The cell line, which was xenografted again to nude mice, produced tumors essentially identical to the original tumor. Furthermore, the cultured cells expressed carbohydrate antigen 19 9 (CA19-9) and carcinoembryonic antigen (CEA) that were secreted in the culture media. This cell line appears to provide a useful system for studying ureteral carcinoma in vivo and in vitro. PMID- 1888705 TI - [Establishment and characterization of endometrial undifferentiated carcinoma cell line (TMCC-2.U)]. AB - We established new cell line designed TMCC-2.U, which suggested transformation to undifferentiated carcinoma, derived from endometrial clear cell carcinoma cell line (TMCC-2). The monolayer culture cell showed a pavement arrangement and spindle like shape. A rough-endoplasmic reticulum, mitochondria etc. are well developed. But cytoplasmic endocrine granulosa were so poorly, it suggests functional developments are poor. The TMCC-2.U cells were transplanted to nude mice which showed no typical pattern suggested undifferentiated carcinoma. Their chromosome number varied and the mode is 78. Marker chromosome were found frequency. Growth pattern and production of tumor marker are clearly differentiate from TMCC-2. As mensioned above, TMCC-2.U cell line will be very valuable in basic research on mechanism of transformation and effects of patient's serum on hystogenesity. PMID- 1888706 TI - [Establishment and characterization of a CA19-9 producing human gastric cancer cell line, STKM-1]. AB - A human gastric cancer cell line, STKM-1, was established from the malignant cells in pleural effusion of a 41-year-old female patient. The primary gastric cancer revealed histologically a poorly differentiated adenocarcinoma. The cells have been cultured with RPMI-1640 medium supplemented with 10% fetal bovine serum and grew as monolayers following a doubling time of 31.4 hour at passage 30. The mode of chromosome number was 52. The STKM-1 cell was tumorigenic in nude mice. The STKM-1 cell cultured in vitro secreted CA19-9, into the medium as a tumor marker. Cells in tumors grown in nude mice were immunohistochemically recognized positively by anti-CA19-9 antibody. The STKM-1 will provide a useful information to clarify the mechanism of CA19-9 secretion. PMID- 1888707 TI - IL-4 down-regulates IL-2 receptor p75 by accelerating its endocytosis. AB - We examined the effects of interleukin 4 (IL-4) on the expression of IL-2 receptor p75 (IL-2R p75) or beta chain on various human T cells. IL-4 promptly down-regulated surface IL-2 receptor (IL-2R) p75 in these cells. Although IL-2 induced IL-2R p75 down-regulation was seen more quickly, IL-2 did not contribute to the process of the IL-4-induced decrease of IL-2R p75. Northern blotting revealed that IL-4 did not reduce the expression of IL-2R p75 mRNA. Studies using Pronase E, which digests cell surface IL-2R p75, or brefeldin A, which blocks intracytoplasmic protein transport from endoplasmic reticulum to the Golgi apparatus, suggest that IL-4-induced IL-2R p75 down-regulation is controlled after IL-2R p75 is expressed on the cell surface. We found that IL-4 accelerated the endocytosis of IL-2R p75, which was monitored by [125I]Mik-beta 3 monoclonal antibody that recognizes non-IL-2-binding epitope on IL-2R p75. These findings demonstrate that IL-4 down-regulates IL-2R p75 mainly by accelerating its endocytosis. PMID- 1888708 TI - The stimulation of lymphocyte motility by cultured high endothelial cells and its inhibition by pertussis toxin. AB - Incubation of rat lymph node lymphocytes with cultured high endothelial cells caused a high proportion of the lymphocytes to lose their round shape and adopt a polar morphology. This shape change was rapid; a substantial increase in the number of polar cells occurred within 15 min. Between 30 and 60% of the lymphocytes became polar. The change was not dependent on protein synthesis. Both lymphocytes which adhered to the cultured high endothelial cells and those which were non-adherent changed shape. Evidence is presented for two pathways for the induction of polarity in non-adherent lymphocytes: (i) transient or weak binding to the high endothelial cells may induce a shape change which persists after lymphocyte detachment and (ii) the high endothelial cells shed or secrete high molecular weight material into the medium which induces the shape change. The rapid change in lymphocyte morphology induced by cultured high endothelial cells was inhibited by pre-incubation of the lymphocytes with low concentrations (4-100 ng/ml) of pertussis toxin. Upon prolonged (2 h) incubation of toxin-treated lymphocytes with cultured endothelial cells a significant proportion of the lymphocytes adhering to the endothelial cells changed shape while the non adherent lymphocytes remained spherical. This implies that cultured high endothelial cells may stimulate lymphocyte motility by two mechanisms: one which is rapid and pertussis toxin sensitive and one which is slower, pertussis toxin insensitive and dependent on lymphocyte adhesion to the high endothelial cells. PMID- 1888709 TI - Regulation of murine in vivo IgG and IgE responses by a monoclonal anti-IL-4 receptor antibody. AB - Although the cytokine interleukin 4 (IL-4) stimulates LPS-activated mouse B lymphocytes to secrete both IgG1 and IgE, an anti-IL-4 antibody completely inhibits IgE responses but has little or no effect on several in vivo IgG responses. IL-4 might, therefore, have a restricted role in the generation of in vivo humoral immune responses. Alternatively, IgG1 responses might be stimulated by IL-4 secreted by T cells that are interacting directly with B cells, so that anti-IL-4 antibody cannot neutralize IL-4 before it binds to a B cell IL-4 receptor. In contrast, an antibody that blocks the IL-4 receptor (IL-4R) should equally inhibit responses to IL-4 produced proximal to or distant from a B cell. This reasoning led us to determine the ability of an anti-IL-4R mAb to affect antibody production in mice injected with a goat antibody to mouse IgD (GaM delta) or inoculated with the nematode parasite Heligmosomoides polygyrus. Anti IL-4R mAb, like anti-IL-4 mAb, blocked IgE responses by greater than 95% and enhanced IgG2a responses to a variable extent. Anti-IL-4R mAb, however, had only a modest and variable inhibitory effect on the induction of IgG1 responses, although it caused these responses to terminate more rapidly. A combination of anti-IL-4 and anti-IL-4R mAbs totally blocked goat anti-mouse IgD antibody (GaM delta)-induced IgE production but had no additive inhibitory effect on IgG1 production. These observations are most consistent with the view that IL-4 is required for a primary IgE response, but has relatively little role in the induction of IgG1 responses in the in vivo systems studied. PMID- 1888710 TI - Room temperature, low-field 13C-n.m.r. spectra of degraded kappa/iota carrageenans. AB - Using samples previously degraded by autohydrolysis, it is possible to obtain valuable low-field 13C-n.m.r. spectra of samples of kappa/iota carrageenans at room temperature. Spectroscopy of samples extracted at different stages of autohydrolysis helps to determine the mechanism of the reaction and the presence of low proportion kinks and other irregularities in the molecules. PMID- 1888711 TI - Structural analysis of turkey tendon collagen upon removal of the inorganic phase. AB - Calcified leg flexor tendons in which the inorganic phase content had been lowered by progressive demineralization were studied by small angle X-ray diffraction and thermogravimetry. The X-ray diffraction results agree very well with the data previously obtained on calcified turkey tendon indicating that the method used to decalcify tendons provides good correspondence with the process of calcification. Up to five thermal processes can be detected in the thermogravimetric scans: (1) water release; (2) collagen decomposition; (3 and 4) combustion of the residual organic components; (5) carbonate removal from the apatitic phase. The temperature of collagen decomposition decreases at lower inorganic phase content in agreement with the higher thermal stability of calcified collagen fibrils compared with uncalcified ones. The decrease of collagen thermal stability upon decalification is paralleled by a decrease of the structural order of the collagen fibrils as indicated by small angle X-ray diffraction data. Decalcification down to about 40% wt of inorganic phase does not significantly alter the inorganic blocks that are regularly arranged inside the gap zone of the collagen. Further removal of inorganic phase down to about 15% wt provokes a variation of the intensity distribution of the small angle meridional reflections that can be ascribed to a reduction of the mean height of the inorganic blocks. At inorganic phase contents below 15% wt the gap region is more free to contract upon air drying as a result of the reduction of the mean length of the inorganic blocks. PMID- 1888712 TI - Molecular transforms of kappa carrageenan and furcellaran from mixed gel systems. AB - X-ray fibre diffraction studies of furcellaran-carob, furcellaran-tara, and furcellaran-konjac mannan mixed gels have failed to reveal any evidence for the predicted intermolecular binding between the algal polysaccharide helix and the galactomannan or glucomannan (konjac) mannan). In the absence of such interactions, mixed gels of kappa carrageenan-konjac mannan and furcellaran konjac mannan, have been used to obtain good quality molecular transforms of the kappa carrageenan and furcellaran molecules in an oriented nematic liquid crystalline form. Analyses of the pattern support double helix structures with threefold symmetry with helix pitch of 2.5 nm. The absence of a 0.83 nm meridional in kappa carrageenan necessitates zero axial translation from the exact half-stagger position, contrary to the model building prediction. An axial translation from half-stagger is necessary for furcellaran. PMID- 1888713 TI - Single crystals of V amylose. AB - Single crystals of V amylose were prepared from dilute solution in water/ethanol over a range of temperatures. The effects of crystallization temperature on crystal morphology and thickness were investigated using transmission electron microscopy. Annealing of these crystals gave rise to large increases in crystal thickness. It is concluded that V amylose crystals behave in a similar way to crystals of linear synthetic polymers. PMID- 1888714 TI - Model for the structure of formaldehyde dehydrogenase based on alcohol dehydrogenase. AB - The three-dimensional structure of rat liver formaldehyde dehydrogenase (FALDH), previously known as class III alcohol dehydrogenase, was constructed using computer graphics and computer programs developed for model building. The construction is based on horse liver alcohol dehydrogenase (EE-ADH), whose structure has been elucidated by X-ray crystallography. The high sequence homology between the two enzymes makes knowledge-based modelling feasible in this case. The model shows a remarkable similarity to horse liver alcohol dehydrogenase especially in the NAD-binding domain. Certain mutations, and the one insertion in FALDH compared to EE-ADH in particular, have cause important changes in the substrate binding site, and thus aliphatic alcohols have been replaced by hemi-thioacetals as favourable substrates. PMID- 1888715 TI - Influence of the substituents of the carboxyl groups and of the rhamnose content on the solution properties and flexibility of pectins. AB - Viscometric measurements were carried out on well-characterized apple, citrus, sugar-beet pectins in order to analyse the effect of the nature and the amount of substituents (methyl, amide, acetyl groups) and of the rhamnose content on the flexibility of the polymeric backbone. Through the dependence of the intrinsic viscosity with the ionic strength the flexibility parameter B was determined. B values between 0.072 and 0.017 indicate that pectins are relatively stiff molecules. However, an increase in flexibility is noticeable with the rise of the rhamnose content and of the amount of amide groups of the pectic acids. The flexibility is also sensitive to the degree of methylation. PMID- 1888716 TI - Accumulation of a poly(hydroxyalkanoate) copolymer containing primarily 3 hydroxyvalerate from simple carbohydrate substrates by Rhodococcus sp. NCIMB 40126. AB - A number of taxonomically-related bacteria have been identified which accumulate poly(hydroxyalkanoate) (PHA) copolymers containing primarily 3-hydroxyvalerate (3HV) monomer units from a range of unrelated single carbon sources. One of these, Rhodococcus sp. NCIMB 40126, was further investigated and shown to produce a copolymer containing 75 mol% 3HV and 25 mol% 3-hydroxybutyrate (3HB) from glucose as sole carbon source. Polyesters containing both 3HV and 3HB monomer units, together with 4-hydroxybutyrate (4HB), 5-hydroxyvalerate (5HV) or 3 hydroxyhexanoate (3HHx), were also produced by this organism from certain accumulation substrates. With valeric acid as substrate, almost pure (99 mol% 3HV) poly(3-hydroxyvalerate) was produced. N.m.r. analysis confirmed the composition of these polyesters. The thermal properties and molecular weight of the copolymer produced from glucose were comparable to those of PHB produced by Alcaligenes eutrophus. PMID- 1888717 TI - Structure of gamma-chymotrypsin in the range pH 2.0 to pH 10.5 suggests that gamma-chymotrypsin is a covalent acyl-enzyme adduct at low pH. AB - Crystals of gamma-chymotrypsin (gamma-CHT) grown at pH 7.0 are stable from pH 2.0 to 11.0. Crystalline gamma-CHT therefore provides an unusually favourable system to observe the structure of a protein and its bound solvent over a broad range of pH. In this report we describe the high-resolution refined structure of gamma-CHT at pH values of 2.0, 7.0 and 10.5. The apparent tetrapeptide seen bound in the active site of gamma-CHT at pH 7.0 is also present at pH 2.0 and 10.5 although it is better defined at low pH. A comparison of the respective structures shows that there is additional electron density in the low pH structure at the point where the side-chain of Ser 195 approaches most closely to the presumptive inhibitor. This suggests that the adduct is most likely to be covalently linked to the enzyme at low pH and to be non-covalent at higher pH. As the pH is lowered from 7.0 to 2.0, the side-chain of His 40 rotates approximately 120 degrees about its C alpha-C beta bond and, in concert, the side-chain of Gln 34 also rotates approximately 140 degrees about its C alpha-C beta bond. Apart from these localized rearrangements in the vicinity of His 40, the structure of gamma-CHT at pH 2.0 is very similar to that at neutral pH. The structure of gamma-CHT at pH 10.5 is also seen to be almost identical with that at neutral pH. There is no indication that the internal salt bridge between Asp 194 and the alpha-amino group of lle 16 begins to dissociate at pH 10.5. With the exception of the vicinity of His 40, the structure of the bound solvent in the crystal structures at low, neutral and high pH is very similar.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1888718 TI - Mapping of isozymic differences in enolase. AB - The existence of the isozymes of non-regulatory enzymes often has been linked to their interaction with other macromolecules. Enolase, a non-regulatory enzyme, has three isozymes for which sequences have been determined in two or more vertebrate species. The positions in the enolase sequences that differ between the isozymes were mapped in the 3-D structure of the enzyme. The positions in a given isozymic form which were not conserved in different species were considered to be resulting from the neutral drift of sequences and rejected. Also, the residues with no accessible surface were rejected. Three areas with relatively high densities of isozymic substitutions were found. We consider them as the likely sites of contact with other macromolecules. PMID- 1888719 TI - Domains, motifs, and linkers in 2-oxo acid dehydrogenase multienzyme complexes: a paradigm in the design of a multifunctional protein. PMID- 1888720 TI - Electron transfer within xanthine oxidase: a solvent kinetic isotope effect study. AB - Solvent kinetic isotope effect studies of electron transfer within xanthine oxidase have been performed, using a stopped-flow pH-jump technique to perturb the distribution of reducing equivalents within partially reduced enzyme and follow the kinetics of reequilibration spectrophotometrically. It is found that the rate constant for electron transfer between the flavin and one of the iron sulfur centers of the enzyme observed when the pH is jumped from 10 to 6 decreases from 173 to 25 s-1 on going from H2O to D2O, giving an observed solvent kinetic isotope effect of 6.9. An effect of comparable magnitude is observed for the pH jump in the opposite direction, the rate constant decreasing from 395 to 56 s-1. The solvent kinetic isotope effect on kobs is found to be directly proportional to the mole fraction of D2O in the reaction mix for the pH jump in each direction, consistent with the effect arising from a single exchangeable proton. Calculations of the microscopic rate constants for electron transfer between the flavin and the iron-sulfur center indicate that the intrinsic solvent kinetic isotope effect for electron transfer from the neutral flavin semiquinone to the iron-sulfur center designated Fe/S I is substantially greater than for electron transfer in the opposite direction and that the observed solvent kinetic isotope effect is a weighted averaged of the intrinsic isotope effects for the forward and reverse microscopic electron-transfer steps.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1888721 TI - Metabolism of low-density lipoprotein free cholesterol by human plasma lecithin cholesterol acyltransferase. AB - The metabolism of cholesterol derived from [3H]cholesterol-labeled low-density lipoprotein (LDL) was determined in human blood plasma. LDL-derived free cholesterol first appeared in large alpha-migrating HDL (HDL2) and was then transferred to small alpha-HDL (HDL3) for esterification. The major part of such esters was retained within HDL of increasing size in the course of lecithin cholesterol acyltransferase (LCAT) activity; the balance was recovered in LDL. Transfer of preformed cholesteryl esters within HDL contributed little to the labeled cholesteryl ester accumulating in HDL2. When cholesterol for esterification was derived instead from cell membranes, a significantly smaller proportion of this cholesteryl ester was subsequently recovered in LDL. These data suggest compartmentation of cholesteryl esters within plasma that have been formed from cell membrane or LDL free cholesterol, and the role for HDL2 as a relatively unreactive sink for LCAT-derived cholesteryl esters. PMID- 1888722 TI - CD2 rocking modes as quantitative infrared probes of one-, two-, and three-bond conformational disorder in dipalmitoylphosphatidylcholine and dipalmitoylphosphatidylcholine/cholesterol mixtures. AB - The use of CD2 rocking modes in the IR spectrum as quantitative probes of phospholipid conformational disorder has recently been described for aqueous dispersions of 1,2-dipalmitoylphosphatidylcholine (DPPC) and DPPC/cholesterol mixtures [Mendelsohn et al. (1989) Biochemistry 28, 8934-8939; Davies et al. (1990) Biochemistry 29, 4368-4373]. Initial studies focused at the 4, 6, and 10 acyl chain positions of DPPC. In the current work, the method is extended to the 2, 3, 12, and 13 positions. Conformational disorder in the L alpha phase is approximately the same (about 20% gauche) at positions 4, 10, and 13, but an unexpected higher value is observed (about 30%) at the 6 position. Cholesterol (33 mol%) restricts gauche rotamer formation by factors ranging from 6 to 9 at positions 4 and 6, respectively, to 1.5-2 at positions 10, 12, and 13. Quantitative analysis for the DPPC/cholesterol "liquid-ordered" phase indicates the occurrence of 1.2 gauche bonds/chain, a marked reduction from the 3.6-4.2 gauche bonds/chain for DPPC alone. Proximity to the ester moiety at acyl chain position 3 perturbs the vibrational coupling patterns of the CD2 rocking modes and eliminates their sensitivity to conformational change. In addition, the feasibility of a method based on the conformation-dependent coupling between CD2 rocking frequencies of two successive CD2 groups for the quantitative detection of specific, position-dependent king (gtg') and isolated gauche (gtt) conformers is demonstrated. Finally, comparisons between IR measurements and explicit theoretical predictions of acyl chain conformational order are presented. PMID- 1888723 TI - Infrared spectroscopic studies on the phosphatidylserine bilayer interacting with calcium ion: effect of cholesterol. AB - Fourier transform infrared (IR) spectroscopic studies of phosphatidylserine/cholesterol/Ca2+ complexes are reported using the synthetic phosphatidylserines (PS) 1,2-dioleoyl-sn-glycero-3-phospho-L-serine (DOPS), 1 palmitoyl-2-oleoyl-sn-glycero-3-phospho-L-serine (POPS), and 1,2-dimyristoyl-sn glycero-3-phospho-L-serine (DMPS). IR spectra reveal that cholesterol does not significantly alter the binding nature of Ca2+ to PS molecules; Ca2+ binds to the phosphate ester group of PS in the presence of cholesterol up to 50 mol% as in the case of pure PS bilayers. However, the IR data indicate that the presence of cholesterol induces disorder of the acyl chain packing, increases the degree of immobilization of the interfacial and polar regions, and increases the degree of dehydration of the PS/Ca2+ complexes. PMID- 1888724 TI - Complete structure of the cell surface polysaccharide of Streptococcus oralis C104: a 600-MHz NMR study. AB - Specific lectin-carbohydrate interactions between certain oral streptococci and actinomyces contribute to the microbial colonization of teeth. The receptor molecules of Streptococcus oralis, 34, ATCC 10557, and Streptococcus mitis J22 for the galactose and N-acetylgalactosamine reactive fimbrial lectins of Actinomyces viscosus and Actinomyces naeslundii are antigenically distinct polysaccharides, each formed by a different phosphodiester-linked oligosaccharide repeating unit. These streptococci all coaggregated strongly with both A. viscosus and A. naesludii strains, whereas S. oralis C104 interacted preferentially with certain strains of the latter species. Receptor polysaccharide was isolated from S. oralis C104 cells and was shown to contain galactose, N-acetylgalactosamine, ribitol, and phosphate with molar ratios of 4:1:1:1. The 1H NMR spectrum of the polysaccharide shows that it contains a repeating structure. The individual sugars in the repeating unit were identified by 1H coupling constants observed in E-COSY and DQF-COSY spectra. NMR methods included complete resonance assignments (1H and 13C) by various homonuclear and heteronuclear correlation experiments that utilize scalar couplings. Sequence and linkage assignments were obtained from the heteronuclear multiple-bond correlation (HMBC) spectrum. This analysis shows that the receptor polysaccharide of S. oralis C104 is a ribitol teichoic acid polymer composed of a linear hexasaccharide repeating unit containing two residues each of galactopyranose and galactofuranose and a residue each of GalNAc and ribitol joined end to end by phosphodiester linkages with the following structure. [----6)Galf(beta 1--- 3)Galp(beta 1----6)Galf(beta 1----6)GalpNAc(beta 1----3) Galp(alpha 1--- 1)ribitol(5----PO4-]n PMID- 1888725 TI - Purification of the endogenous glucocorticoid receptor stabilizing factor. AB - A ubiquitous, low molecular weight, heat-stable component of cytosol stabilizes the glucocorticoid receptor in its untransformed state in association with hsp90. This heat-stable factor mimics molybdate in its effects on receptor function, and it has the heat stability, charge, and chelation properties of a metal oxyanion [Meshinchi, S., Grippo, J.F., Sanchez, E.R., Bresnick, E.H., & Pratt, W.B. (1988) J. Biol. Chem. 263, 16809-16817]. In this paper, we describe the further purification of the endogenous factor from rat liver cytosol by anion-exchange HPLC (Ion-110) after prepurification by molecular sieving, cation absorption, and charcoal absorption. Elution of the factor with an isocratic gradient of ammonium bicarbonate results in recovery of all of the bioactivity in a single peak which coelutes with inorganic phosphate and contains all of the endogenous molybdenum. The bioactivity can be separated from inorganic phosphate by chromatography of the partially purified endogenous factor on a metal-chelating column of Chelex 100. The chelating procedure results in complete loss of bioactivity with recovery of 98% of the inorganic phosphate in both the column drop-through and a subsequent 1 M NaCl wash. The factor preparation purified through the Ion-110 HPLC step inhibits temperature-mediated dissociation of the immunopurified glucocorticoid receptor-hsp90 complex, but it is considerably more effective at stabilizing the unpurified receptor-hsp90 complex in a Chelex-treated cytosol system that has been depleted of metal components. These observations support the proposal that an endogenous metal can stabilize the binding of hsp90 to the receptor but it is likely that other cytosolic components that are not present in the immunopurified complex must contribute to the stability of the soluble protein-protein complex in cytosol. PMID- 1888726 TI - Mutations in endonuclease V that affect both protein-protein association and target site location. AB - A general mechanism by which proteins locate their target sites within large domains of DNA is a one-dimensional facilitated diffusion process in which the protein scans DNA in a nonspecifically bound state. An electrostatic contribution to this type of mechanism has been previously established. This study was designed to question whether other characteristics of a protein's structure might contribute to the scanning mechanism of target site location. In this regard, T4 endonuclease V was shown to establish an ionic strength dependent monomer-dimer equilibrium in solution. A protein dimer interaction site was postulated to exist along a putative alpha-helix containing amino acid residues 54-62. The conservative substitutions of Phe-60----Leu-60 and Phe-59, Phe-60----Leu-59, Leu 60 resulted in mutant enzymes which remained in the monomeric state independent of the ionic strength of the solution. The target site location mechanism of these mutants has also been altered. Under conditions where wild-type endonuclease V processively scans nontarget DNA, the target location mechanism of the monomeric mutant proteins was shifted toward a less processive search. This decrease in the processivity of the mutants was especially surprising because the nontarget DNA binding affinity was found to be significantly increased. Thus, an additional component of the endonuclease V DNA scanning mechanism appears to be the formation of a stable endonuclease V dimer complex. PMID- 1888727 TI - Quadruplex DNA formation in a region of the tRNA gene supF associated with hydrogen peroxide mediated mutations. AB - A hot spot for H2O2/Fe-mediated mutation has been observed between bases 154 and 170 of the supF gene in the mutation reporter plasmid pZ189 [Moraes et al. (1990) Carcinogenesis 11, 283; Akman et al. (1991) Mutat. Res. (in press)]. To further characterize this hot spot, we synthesized the 33mer d(pAAAGTGATGGTGGTGGGGGAAGGATTCGAACCT) (pZ33), which is complementary to bases 159 191 of the supF gene. pZ33 annealed spontaneously in 10 mM Tris-HCl (pH 8.0)-1 mM EDTA-100 mM NaCl at 50 degrees C into two major forms, one of which migrates more slowly than does d(pT)33 on nondenaturing 12% polyacrylamide gels. We propose that this form is a four-stranded structure stabilized by Hoogsteen-type deoxyguanosine quartets involving all deoxyguanosines of the sequence d (pGGTGGTGGGGG) because of the following. (1) pZ33 migrates as a single form that comigrates with d(pT)33 on denaturing 20% acrylamide-8 M urea gels. (2) Annealing an equimolar mixture of 5'-32P-labeled pZ33 and the oligodeoxynucleotide d(pTTTTTTTTpZ33TTTTTTTT) (pZ49), as well as 5'-32P-labeled pZ49 and pZ33, caused the formation of four, discreet slowly migrating bands on nondenaturing 12% polyacrylamide gels. Mixing 5'-32P-labeled pZ33 with 5'-32P-labeled pZ49 resulted in five slowly migrating bands. (3) An oligodeoxynucleotide identical with pZ33 except that every deoxyguanosine has been replaced with deoxyinosine did not anneal into a slowly migrating form. (4) Dimethyl sulfate protection studies demonstrated that all deoxyguanosines of the sequence d(pGGTGGTGGGGG) were protected at N-7 in the slowly migrating form but not in single-stranded pZ33. These data suggest that a hot spot for H2O2/Fe-mediated base substitutions is located adjacent to a sequence that can spontaneously adopt a quadruplex structure in which deoxyguanosine quartets are Hoogsteen bonded. PMID- 1888728 TI - Photooxidation of specific residues in alpha-crystallin polypeptides. AB - Singlet oxygen is a biologically important, photochemically generated species that preferentially oxidizes His, Trp, and Met residues of protein molecules. Calf alpha-crystallin was photooxidized with use of meso-tetra(p sulfonatophenyl)porphyrin (TPPS) and uroporphyrin (UP) as singlet oxygen generators. The effects of photooxidation were monitored by analyzing the changes in alpha-crystallin peptide maps obtained by reversed-phase HPLC using a photodiode array absorbance detector. The reaction led to the loss of six specific peptides, five of which contained photooxidizable residues. Peptides containing His-97 and His-154 from the A chain and Met-68 from the B chain are preferentially photooxidized, suggesting that those residues have access to singlet oxygen. Trp residues in the N-terminal region are converted to NFK, whereas Trp-60 in the B chain is not photooxidized strongly suggesting that the former are close to the surface of alpha-crystallin while the latter Trp residue is buried. Only one peptide that is lost from the peptide maps does not contain a photooxidizable group; however, this peptide does contain an apparently undigested Lys residue. It is suggested that it forms a cross-link with a photooxidized His residue. PMID- 1888729 TI - Catalytic mechanism of NADP(+)-dependent isocitrate dehydrogenase: implications from the structures of magnesium-isocitrate and NADP+ complexes. AB - The structures of NADP+ and magnesium isocitrate bound to the NADP(+)-dependent isocitrate dehydrogenase of Escherichia coli have been determined and refined at 2.5-A resolution. NADP+ is bound by the large domain of isocitrate dehydrogenase, a structure that has little similarity to the supersecondary structure of the nucleotide-binding domain of the lactate dehydrogenase-like family of nucleotide binding proteins. The coenzyme-binding site confirms the fundamentally different evolution of the isocitrate dehydrogenase-like and the lactate dehydrogenase-like classes of nucleotide-binding proteins. In the magnesium-isocitrate complex, magnesium is coordinated to the alpha-carboxylate and alpha-hydroxyl oxygen of isocitrate in a manner suitable for stabilization of a negative charge on the hydroxyl oxygen during both the dehydrogenation and decarboxylation steps of the conversion of isocitrate to alpha-ketoglutarate. The metal ion is also coordinated by aspartate side chains 283' (of the second subunit of the dimer) and 307 and two water molecules in a roughly octahedral arrangement. On the basis of the geometry of the active site, the base functioning in the dehydrogenation step is most likely aspartate 283'. E. coli isocitrate dehydrogenase transfers a hydride stereospecifically to the A-side of NADP+, and models for a reactive ternary complex consistent with this stereospecificity are discussed. PMID- 1888730 TI - Determination of the three-dimensional solution structure of barnase using nuclear magnetic resonance spectroscopy. AB - The solution conformation of the ribonuclease barnase has been determined by using 1H nuclear magnetic resonance (NMR) spectroscopy. The 20 structures were calculated by using 853 interproton distance restraints obtained from analyses of two-dimensional nuclear Overhauser spectra, 72 phi and 53 chi 1 torsion angle restraints, and 17 hydrogen-bond distance restraints. The calculated structures contain two alpha-helices (residues 6-18 and 26-34) and a five-stranded antiparallel beta-sheet (residues 50-55, 70-75, 85-91, 94-101, and 105-108). The core of the protein is formed by the packing of one of the alpha-helices (residues 6-18) onto the beta-sheet. The average RMS deviation between the calculated structures and the mean structure is 1.11 A for the backbone atoms and 1.75 A for all atoms. The protein is least well-defined in the N-terminal region and in three large loops. When these regions are excluded, the average RMS deviation between the calculated structures and the mean structure for residues 5 34, 50-56, 71-76, 85-109 is 0.62 A for the backbone atoms and 1.0 A for all atoms. The NMR-derived structure has been compared with the crystal structure of barnase [Mauguen et al. (1982) Nature (London) 297, 162-164]. PMID- 1888731 TI - Human erythrocyte glutathione reductase: chemical mechanism and structure of the transition state for hydride transfer. AB - Kinetic parameters and primary deuterium kinetic isotope effects for NADH and five pyridine nucleotide substrates have been determined at pH 8.1 for human erythrocyte glutathione reductase. DV/KNADH and DV are equal to 1.4 and are pH independent below pH 8.1, but DV decreases to 1.0 at high pH as a group exhibiting a pK of 8.6 is deprotonated. This result suggests that as His-467' is deprotonated, the rate of the isotopically insensitive oxidative half-reaction is specifically decreased and becomes rate-limiting. For all substrates, equivalent V and V/K primary deuterium kinetic isotope effects are observed at pH values below 8.1. The primary deuterium kinetic isotope effect on V, but not V/K, is sensitive to solvent isotopic composition. The primary tritium kinetic isotope effects agree well with the corresponding value calculated from the primary deuterium kinetic isotope effects by using the Swain-Schaad relationship. This suggests that the primary deuterium kinetic isotope effects observed in these steady-state experiments are the intrinsic primary deuterium kinetic isotope effects for hydride transfer. The magnitude of the primary deuterium kinetic isotope effect is dependent on the redox potential of the pyridine nucleotide substrate used, varying from approximately 1.4 for NADH and -320 mV reductants to 2.7 for thioNADH to 4.2-4.8 for 3-acetylpyridine adenine dinucleotide (3APADH). The alpha-secondary tritium kinetic isotope effects also increase as the redox potential of the pyridine nucleotide substrate becomes more positive. Together, these data indicate that the transition state for hydride transfer is very early for NADH and becomes later for thioNADH and 3APADH, as predicted by Hammond's postulate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1888732 TI - Zinc inhibition of renin and the protease from human immunodeficiency virus type 1. AB - We report here for the first time that Zn2+ is an effective inhibitor of renin and the protease from HIV-1, two aspartyl proteinases of considerable physiological importance. Inhibition of renin is noncompetitive and is accompanied by binding of 1 mol of Zn2+/mol of enzyme. Depending on the substrate, inhibition of the HIV protease by Zn2+ can be either competitive or noncompetitive, but in neither case is loss of activity due to disruption of the protease dimer. Inhibition of both enzymes is first order with respect to Zn2+ and is rapidly reversed by addition of EDTA. Ki values are strongly pH dependent and optimal in the range of 20 microM at or above pH 7. All of the data in hand suggest that the inhibitory effect of Zn2+ is a consequence of its binding at, or near, the active-site carboxyl groups of these aspartyl proteinases. This inhibition of the viral enzyme may help to explain some of the beneficial effects seen in AIDS patients who have received Zn2+ therapy. PMID- 1888733 TI - Unusual binding of ethidium to a deoxyoligonucleotide containing a B-Z junction. AB - Equilibrium binding studies are reported that describe the interaction of the simple intercalator ethidium with a hexadecadeoxynucleotide (BZ-1) that contains a stable B-Z junction. The transition of BZ-1 from its low-salt right-handed form to its high-salt hybrid form containing the junction between left- and right handed DNA was found to greatly facilitate ethidium binding. Ethidium binding to all conformational forms of BZ-1 was found to be complex and highly cooperative, a result that indicates an unusually robust conformational mobility in the molecule. Binding results were quantitatively analyzed by using an allosteric model that provides a description of energetics of the conformational transitions in BZ-1, in addition to estimates of the binding constants for ethidium binding to the different conformations. These results provide a quantitative description of a structurally specific intercalator-DNA interaction. PMID- 1888734 TI - Mechanisms of mutagenesis by exocyclic DNA adducts. Construction and in vitro template characteristics of an oligonucleotide bearing a single site-specific ethenocytosine. AB - By using a gene-targeted random DNA adduction approach, we have recently shown that chloroacetaldehyde, a metabolite of vinyl chloride, induces mutations predominantly at cytosines under conditions in which both ethenoadenine (epsilon A) and ethenocytosine (epsilon C) are formed. Although the observed mutational specificity of epsilon C suggested that it was a noninstructional lesion, the high efficiency of mutagenesis and an apparent lack of SOS dependence were reminiscent of mispairing lesions. To obtain more direct evidence showing that epsilon C has properties of a noninstructional mutagenic lesion, we have examined the in vitro template properties of a single epsilon C residue at a unique position in a synthetic oligonucleotide. The oligonucleotide was constructed by use of the following steps: (a) in vitro treatment of the pentameric oligodeoxyribonucleotide TTCTT with chloroacetaldehyde to convert the central cytosine to ethenocytosine; (b) purification and characterization of TT epsilon CTT; and (c) ligation of purified TT epsilon CTT to two decamers to create a 25 nt long oligodeoxyribonucleotide with a centrally located epsilon C residue. The template characteristics of epsilon C were examined by the annealing of end labeled primers to the purified epsilon C-containing oligonucleotide and primer elongation by Escherichia coli DNA polymerase I in the presence of one or more nucleotide precursors. The elongation products were analyzed by high-resolution gel electrophoresis followed by autoradiography and quantitated by computing densitometry.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1888735 TI - Mechanisms of mutagenesis by exocyclic DNA adducts. Transfection of M13 viral DNA bearing a site-specific adduct shows that ethenocytosine is a highly efficient RecA-independent mutagenic noninstructional lesion. AB - It is widely accepted that mutagenic DNA lesions fall into two categories: mispairing lesions hydrogen bond with an incorrect incoming base, generally do not stop replication, and possess high mutagenic efficiency without any requirement for induced functions; noninstructional lesions lack accessible template information, act as strong blocks to DNA replication (and are therefore toxic), and their mutagenic effects are SOS-dependent. Our recent results show that ethenocytosine (epsilon C), a noninstructional exocyclic DNA lesion induced by vinyl chloride, may have unusual mutagenic properties. To obtain more definitive experimental evidence for the observed effects, we have introduced a single epsilon C residue at a specific site of coliphage M13AB28 replicative form DNA by a "single-stranded linker-ligation" technique. The resulting DNA was purified and transfected into appropriate recA+ or recA- Escherichia coli host cells. The effect of epsilon C on survival was determined from transfection efficiency. Both the frequency and specificity of mutations induced by epsilon C were determined by direct sequence analysis of randomly picked progeny phage plaques. The results indicated that epsilon C has little effect on the survival of M13 DNA. Approximately 30% of the progeny phage obtained by transfecting epsilon C DNA had a base substitution mutation precisely at the lesion site. No such mutations were observed in progeny plaques obtained by transfecting the control DNA construct. All epsilon C-induced mutations were either C-to-T transitions or C-to-A transversions. Neither survival nor mutagenic efficiency was significantly affected in recA- host cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1888736 TI - Interaction of DNA with the Klenow fragment of DNA polymerase I studied by time resolved fluorescence spectroscopy. AB - The interaction of a fluorescent duplex DNA oligomer with the Klenow fragment of DNA polymerase I from Escherichia coli has been studied in solution by using time resolved fluorescence spectroscopy. An aminonaphthalenesulfonate (dansyl) fluorescent probe was linked by a propyl chain to a C5-modified uridine base located at a specific site in the primer strand of the DNA oligomer. The fluorescent oligomer bound tightly to the Klenow fragment (KD = 7.9 nM), and the probe's position within the DNA-protein complex was varied by stepwise elongation of the primer strand upon addition of the appropriate deoxynucleoside triphosphates. The decay of the total fluorescence intensity and the polarization anisotropy were measured with a picosecond laser and a time-correlated single photon counting system. The fluorescence lifetimes, the correlation time for internal rotation, and the angular range of internal rotation varied according to the probe's position within the DNA-protein complex. These results showed that five or six bases of the primer strand upstream of the 3' terminus were in contact with the protein and that within this contact region there were differences in the degree of solvent accessibility and the closeness of contact. Further, a minor binding mode of the DNA-protein complex was identified, on the basis of heterogeneity of the probe environment observed when the probe was positioned seven bases upstream from the primer 3' terminus, which resulted in a distinctive "dip and rise" in the anisotropy decay. Experiments with an epoxy terminated DNA oligomer and a site-directed mutant protein established that the labeled DNA was binding at the polymerase active site (major form) and at the spatially distinct 3'----5' exonuclease active site (minor form). The abundance of each of these distinct binding modes of the DNA-protein complex was estimated under solution conditions by analyzing the anisotropy decay of the dansyl probe. About 12% of the labeled DNA was bound at the 3'----5' exonuclease site. This method should be useful for investigating the editing mechanism of this important enzyme. PMID- 1888737 TI - Insight into the conformational dynamics of specific regions of porcine pancreatic phospholipase A2 from a time-resolved fluorescence study of a genetically inserted single tryptophan residue. AB - The effects of Ca2+ and substrate analogue binding on the conformational dynamics of porcine pancreas phospholipase A2 (PLA2) in different regions was explored by combining site-directed mutagenesis and time-resolved fluorescence measurements. The single tryptophan residue (Trp-3) of the wild-type protein (W3), in the alpha helix A, was replaced by a phenylalanine residue (W3F), whereafter Trp was substituted either for leucine-31 (W31), located in the calcium binding loop, or for phenylalanine-94 (W94), located at the "back side" of the enzyme. Furthermore, mutants lacking the 62-66 sequence were constructed with the Trp at position 3 (delta W3) or 31 (delta W31). The total fluorescence intensity decays of Trp in each protein, in the protein-calcium and the protein-calcium-substrate analogue complexes, analyzed by the maximum entropy method (MEM) can be interpreted as distributions of separated lifetime classes. In the case of the W94 mutant, a major short-lived excited-state population (tau approximately 50 ps) is observed, probably deactivated by the interaction with two proximate disulfide bridges via a radiationless process. For the four other mutants, the respective barycenters of the four lifetime classes display comparable values, but the amplitude distributions are different for Trp-3 and Trp-31. The rotational mobility of the Trp residue varies along the peptide chain. Trp-3 experiences only a fast hindered motion. Trp-31 is sensitive to an additional local flexibility that is absent in the N-terminal part of the protein. The largest wobbling angle is observed at position 94. No effect of calcium binding occurs on the lifetime distribution of the Trp-3 and Trp-94 residues. Their mobilities are not affected. In contrast, calcium binding displays a strong influence on the excited-state population distribution of Trp-31. A major population decaying with the longest lifetime is selected in the W31 protein and contributes to approximately 50% of the decay. The local flexibility and the amplitude of motion of Trp-31 is wider in the protein-calcium complex than in the unliganded protein. Binding of the monomeric substrate analogue n dodecylphosphocholine (C12PN) in the presence of calcium slightly affects the Trp 3 excited-state population distribution and its mobility. Trp-31 is more sensitive to this binding. In particular, a more restricted rotation of the Trp 31 residue and a decrease of the peptide local flexibility as protein-calcium complexes are observed in both the W31 and delta W31 mutants.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1888738 TI - How accurately can oligonucleotide structures be determined from the hybrid relaxation rate matrix/NOESY distance restrained molecular dynamics approach? AB - The accuracy and precision of structures derived from a combined hybrid relaxation rate matrix/NOESY distance restrained molecular dynamics methodology were examined with simulations that included typical experimental errors. NOESY data were simulated for a DNA dodecamer duplex, d-(CGCGAATTCGCG)2, with added volume error of approximately 20% and low-level thermal noise. Distances derived from a hybrid relaxation matrix analysis of the NOE data were used as constraints in molecular dynamics driven structural refinements of several initial model geometries. The final structures were compared against results obtained from the traditional isolated two-spin approximation treatment of these NOESY volumes and also against refined structures that employed error-free data. Results show that the structures derived from the relaxation rate matrix analysis of the NOESY data are more accurate than those derived from a simple two-spin approximation analysis and it is possible to achieve refinement to the level of simulated experimental error. Results may be significantly improved with the use of either more accurately measured NOESY volumes or additional matrix-derived constraints. Many of the helical parameters and backbone torsional angles may be accurately reproduced by the hybrid matrix methodology. PMID- 1888739 TI - Effect of metal ion binding on the secondary structure of bovine alpha lactalbumin as examined by infrared spectroscopy. AB - We have examined the influence of monovalent and divalent cations on the secondary structure of bovine alpha-lactalbumin at neutral pH using Fourier transform infrared spectroscopy. Our present studies are based on previously reported amide I' component band assignments for this protein [Prestrelski, S. J., Byler, D. M., & Thompson, M. P. (1991) Int. J. Pept. Protein Res. 37, 508 512]. The results indicate that upon dissolution, alpha-lactalbumin undergoes a small, but significant, time-dependent conformational change, regardless of the ions present. Additionally, these studies provide the first quantitative measure of the well-known secondary structural change which accompanies calcium binding. Results indicate that removal of Ca2+ from holo alpha-lactalbumin results in local unfolding of the Ca(2+)-binding loop; the spectra indicate that approximately 16% of the backbone chain changes from a rigid coordination complex to an unordered loop. We have also examined the effects of binding of several other metal ions. Our studies have revealed that binding of Mn2+ to apo alpha lactalbumin (Ca(2+)-free), while inducing a small, but significant, conformational change, does not cause the alpha-lactalbumin backbone conformation to change to that of the holo (Ca(2+)-bound) form as characterized by infrared spectroscopy. Similar changes to those induced by Mn2+ are observed upon binding of Na+ to apo alpha-lactalbumin, and furthermore, even at very high concentrations (0.2 M), Na+ does not stabilize a structure similar to the holo form. Binding of Zn2+ to the apo form of alpha-lactalbumin does not result in significant backbone conformational changes, suggesting a rigid Zn(2+)-binding site.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1888740 TI - Raman spectroscopic studies of NAD coenzymes bound to malate dehydrogenases by difference techniques. AB - We report here on the Raman spectra of NADH, 3-acetylpyridine adenine dinucleotide, APAD+, and a fragment of these molecules, adenosine 5'-diphosphate ribose (ADPR) bound to the mitochondrial (mMDH) and cytoplasmic (or soluble, sMDH) forms of malate dehydrogenase. We observe changes in the Raman spectrum of the adenosine moiety of these cofactors upon binding to mMDH, indicating that the binding site is hydrophobic. On the other hand, there is little change in the spectrum of the adenosine moiety when it binds to sMDH. Such observations are in clear contrast with those results obtained in LDH and LADH, where there are significant changes in the spectrum of the adenosine moiety when it binds to these two proteins. A strong hydrogen bond is postulated to exist between amide carbonyl group of NAD+ and the enzyme in the binary complexes with both mMDH and sMDH on the basis of a sizable decrease in the frequency of the carbonyl double bond. The interaction energy for formation of a hydrogen bond is the same as found previously for LDH, and we estimate that it is 2.8 kcal/mol more favorable in the binary complex than in water. A hydrogen bond is also detected between the amide-NH2 group of NADH and sMDH that is stronger than that formed in water and is of the same size as found in LDH. Surprisingly, the hydrogen bond to the -NH2 group in mMDH is the same as that found for water.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1888741 TI - Parvalbumin isoforms in chicken muscle and thymus. Amino acid sequence analysis of muscle parvalbumin by tandem mass spectrometry. AB - Parvalbumins are high-affinity Ca(2+)-binding proteins characterized by an EF hand structure. Muscles of lower vertebrates contain up to five isoparvalbumins whereas higher vertebrates were believed to contain only one isoform per species. Recently Brewer et al. [Brewer, J.M., Wunderlich, J.K., & Ragland, W. (1990) Biochimie 72, 653-660] purified and sequenced a protein that they named avian thymic hormone, from chicken thymus. This protein, promoting immunological maturation of bone marrow cells in culture, was identified as a parvalbumin. The amino acid composition of this thymic parvalbumin was, however, considerably different from those of chicken muscle parvalbumin [Strehler, E.E., Eppenberger, H.M., & Heizman, C.W. (1977) FEBS Lett. 75, 127-133], suggesting the existence of two tissue-specific parvalbumins in chicken. We purified parvalbumin from chicken muscle, determined its complete amino acid sequence by tandem mass spectrometry, and showed that this protein is rather homologous to muscle parvalbumins from other species but different in 45 positions from the thymic parvalbumin. We discuss the possibility that a parvalbumin gene family might exist in higher vertebrates, expressed in a tissue-specific and developmentally regulated manner. PMID- 1888742 TI - Associative behavior of the histone (H3-H4)2 tetramer: dependence on ionic environment. AB - Mixtures of histones H3 and H4 were examined by analytical ultracentrifugation and circular dichroism to determine their association behavior and secondary structure content in high and low ionic strength solvents containing chloride, phosphate, or sulfate. H3 and H4 were also cross-linked by using DSP in order to directly trap any intermolecular interactions occurring in solution. While H3 and H4 can exist as an H3-H4 dimer under limited conditions, they behave as a stable (H3-H4)2 tetramer under most conditions, particularly those which are physiologically relevant. In chloride-containing solutions, the equilibrium between H3-H4 and (H3-H4)2 is responsive to changes in ionic strength and paralleled by large changes in alpha-helicity. In sulfate- and phosphate containing solutions, the equilibrium is again governed by ionic strength, but there are no significant changes in secondary structure accompanying shifts in the equilibrium. Small oligomers can be formed in the presence of sulfate and phosphate and trapped by the cross-linking reagent; these oligomers are much smaller than those formed in chloride-containing solutions. However, addition of the H2A-H2B dimer into the system prevents aggregation of the (H3-H4)2 tetramer by acting as a "molecular cap" and thus regulating the assembly pathway toward the formation of tripartite octamers. The observed assembly of H3 and H4 into a stable, tetrameric complex supports the concept of the core histone octamer having a tripartite organization in solution rather than being organized as two heterotypic tetramers. PMID- 1888743 TI - Structural organization of aldehyde dehydrogenases probed by limited proteolysis. AB - Incubation of cytosolic and mitochondrial aldehyde dehydrogenases with trypsin or Glu-C protease under native conditions causes a time-dependent loss of dehydrogenase activity and the production of protein fragments. For evaluation of the results, termination of the reactions with a specific protease inhibitor is especially important in the case of the Glu-C protease. Cleavage site determination by SDS/polyacrylamide gel electrophoresis and sequence analysis identified protease-sensitive amino acid residues at two internal regions spanning positions 248-268 (region 1) and 397-399 (region 2) and at positions in the N-terminal segment (region 3). Region 1 encompasses several cleavages and is sensitive to both proteases in both aldehyde dehydrogenases. Further, it is in a conserved segment and correlates with reactive residues and regions ascribed functional roles. It also correlates with exon borders in the corresponding genes. Combined, the results define region 1 as an important and highly accessible segment of the protein. Region 2 is also adjacent to a conserved segment but lacks further correlation with special properties and appears just to represent an accessible region. The internally cleaved subunits retain a tetrameric configuration as calculated from exclusion chromatography and polyacrylamide gel electrophoresis under native conditions, suggesting that the quaternary structure is not dependent on covalently linked domains within the subunits. Furthermore, the fragments can bind to AMP-Sepharose, suggesting that some functional properties are retained within the cleaved tetramers. However, cleavage at position 35 appears to cause a large fragment (36-263) to be released from the tetramer, suggesting a role of an N-terminal segment or arm (at or before region 3) in subunit interactions. PMID- 1888744 TI - Carbon-13 and deuterium isotope effects on the reaction catalyzed by glyceraldehyde-3-phosphate dehydrogenase. AB - Carbon-13 and deuterium isotope effects have been measured on the reaction catalyzed by rabbit muscle glyceraldehyde-3-phosphate dehydrogenase in an effort to locate the rate-limiting steps. With D-glyceraldehyde 3-phosphate as substrate, hydride transfer is a major, but not the only, slow step prior to release of the first product, and the intrinsic primary deuterium and 13C isotope effects on this step are 5-5.5 and 1.034-1.040, and the sum of the commitments to catalysis is approximately 3. The 13C isotope effects on thiohemiacetal formation and thioester phosphorolysis are 1.005 or less. The intrinsic alpha-secondary deuterium isotope effect at C-4 of the nicotinamide ring of NAD is approximately 1.4; this large normal value (the equilibrium isotope effect is 0.89) shows tight coupling of hydrogen motions in the transition state accompanied by tunneling. With D-glyceraldehyde as substrate, the isotope effects are similar, but the sum of commitments is approximately 1.5, so that hydride transfer is more, but still not solely, rate limiting for this slow substrate. The observed 13C and deuterium equilibrium isotope effects on the overall reaction from the hydrated aldehyde are 0.995 and 1.145, while the 13C equilibrium isotope effect for conversion of a thiohemiacetal to a thioester is 0.994, and that for conversion of a thioester to an acyl phosphate is 0.997. Somewhat uncertain values for the 13C equilibrium isotope effects on aldehyde dehydration and formation of a thiohemiacetal are 1.003 and 1.004. PMID- 1888745 TI - Mechanism of serpin action: evidence that C1 inhibitor functions as a suicide substrate. AB - Serpins form a family of structurally related proteins, many of which function in plasma as inhibitors of serine proteases involved in inflammation, blood coagulation, fibrinolysis, and complement activation. To further characterize the mechanism by which serpins inhibit their target enzymes, we have studied the effect of temperature on the reaction of C1 inhibitor and the serine protease plasma kallikrein. At both 38 and 4 degrees C, C1 inhibitor (Mr 105,000) is cleaved by alpha-kallikrein (Mr 85,000 and 88,000) at position P1 (Arg444) of the reactive center, a reaction that leads to the formation of a covalent bimolecular enzyme-serpin complex (Mr 195,000) and cleaved but uncomplexed serpin (Mr 95,000). Between 38 and 4 degrees C, the product distribution is temperature dependent, with more cleaved C1 inhibitor (Mr 95,000) formed at lower temperatures and correspondingly less Mr 195,000 complex. Studies employing intrinsic tryptophan fluorescence and 1H NMR spectroscopy show that this behavior is not caused by temperature-dependent conformational changes of kallikrein or C1 inhibitor. C1 inhibitor also behaves in this manner with the light chain of kallikrein and, to a lesser extent, with plasmin and C1s. These data are best explained by a branched reaction pathway, identical with the scheme describing the mechanism of action of suicide substrates. This scheme involves the formation of an enzyme-inhibitor intermediate, which can be stabilized into a covalent complex and/or dissociate into free enzyme and cleaved inhibitor, depending on the reaction conditions. PMID- 1888746 TI - Thioltransferase in human red blood cells: kinetics and equilibrium. AB - Thioltransferase from human red blood cells (HRBC TTase), coupled to GSSG reductase, catalyzed glutathione (GSH)-dependent reduction of prototype substrates hydroxyethyl disulfide (HEDS) and sodium S-sulfocysteine as well as of other homo- and heterodisulfides, including the protein mixed disulfide albumin-S S-cysteine. Whereas apparent KM values for the substrates varied over more than a 20-fold range, the Vmax values agreed quite closely, usually within less than a factor of 2, suggesting that initial interaction of oxidized substrate with enzyme is not rate determining. HRBC TTase was inactivated by iodoacetamide (IAA), and this was prevented by pretreatment with disulfides. The pH dependence of IAA inactivation gave a remarkably low apparent pKa of 3.5, which was independent of ionic strength (0.05-2 M). At pH 6, one radiolabeled carboxyamidomethyl moiety was bound to the enzyme after treatment with [14C]IAA. This unusual thiol reactivity suggests that the active-site cysteine moiety of the TTase may be involved in a hydrogen bond with a carboxylate moiety. In contrast, the pH dependence for GSH-dependent TTase catalysis of disulfide reduction displayed an inflection point near pH 8.0, also suggesting that the initial reaction of oxidized substrate with the active-site thiol is not involved in rate determination. Two substrate kinetic studies of HRBC TTase and rat liver TTase (e.g., [GSH] and [HEDS] varied independently) gave patterns of intersecting lines on double-reciprocal plots (1/v vs 1/S), indicating a sequential mechanism for the TTase reactions, rather than a ping-pong mechanism.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1888747 TI - Synthesis, isolation, and characterization of endogenous beta-galactoside-binding lectins in human leukocytes. AB - Galaptin, a beta-galactoside-binding lectin, was isolated from human buffy coat cells (peripheral leukocytes) and spleen by affinity chromatography. The molecular weight (32K) of the native buffy coat galaptin was similar to that for splenic galaptin. Their subunit molecular weight (14.5K), pI (4.60-4.85), and amino acid composition were identical. Both galaptins showed the presence of a single polypeptide when subjected to reversed-phase HPLC. Monospecific rabbit polyclonal antiserum raised against the 14.5-kDa subunit of splenic galaptin reacted with a 14.5-kDa polypeptide present in buffy coat cells, Epstein-Barr virus-immortalized B lymphoblastoid cells, and HL-60 promyelocytic leukemia cells. However, galaptin was not synthesized in vitro by buffy coat cells. Rather, a monomeric beta-galactoside-binding protein of Mr 15.5-16.5K that is immunologically distinct from galaptin was synthesized. This galactoside-binding protein was separable from galaptin by polyacrylamide gel electrophoresis and by anion-exchange chromatography. In contrast, immunoprecipitation experiments confirmed that galaptin was synthesized by the B lymphoblastoid cells. cDNA corresponding to the B lymphoblastoid cell mRNA encoding galaptin was amplified by the polymerase chain reaction. The amplified product was partially sequenced, and 299 nucleotides were identified. The derived amino acids corresponded to residues 6-65, 84-114, and 118-126 found to be present in human splenic galaptin. Immunohistochemical analyses revealed that galaptin was distributed throughout the cytoplasm of B lymphoblastoid cells rather than being localized to the cell surface.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1888748 TI - Enzymatic redox chemistry: a proposed reaction pathway for the six-electron reduction of SO3(2-) to S2- by the assimilatory-type sulfite reductase from Desulfovibrio vulgaris (Hildenborough). AB - A detailed reaction pathway for the six-electron reduction of SO3(2-) to S2- by the assimilatory-type sulfite reductase (SiR) from Desulfovibrio vulgaris (Hildenborough) has been deduced from experiments with 35S-labeled enzyme and the relative reaction rates of nitrogenous substrates. The ligand bridging the prosthetic [Fe4S4]-siroheme center is apparently exchanged by 35S2- in both oxidized and reduced enzyme. This 35S2- label was retained in the course of SO3(2 ) reduction, implicating substrate binding to the nonbridging axial site of the siroheme. A reaction mechanism is proposed in which SO3(2-) binds to Fe2+ through the sulfur atom, followed by a series of two-electron reductive cleavages of S-O bonds. Protonation of oxygen facilitates bond cleavage, giving hydroxide as leaving group. The bridge remains intact throughout the course of the reaction, providing an efficient coupling pathway for electron transfer between the cluster and siroheme. PMID- 1888749 TI - Immunohistochemical localization, purification, and characterization of human urinary bladder glutathione S-transferases. AB - This study describes immunohistochemical localization, purification and characterization of glutathione S-transferase (GST) of human urinary bladder. Even though all the three major classes of isoenzymes (alpha, mu, and pi) were expressed in human bladder, more than 90% of total GST activity was accounted for by a pi class anionic form. Human bladder alpha, mu, and pi class GSTs were immunologically related to respective isoenzymes of other human tissues. GST pi was present in all 13 samples analyzed, whereas GST alpha and mu were detected in nine and eleven samples, respectively. GST alpha of human bladder appeared to be unique, because unlike this class of GSTs of other human tissues, bladder enzyme had lower affinity for GSH linked to epoxy-activated Sepharose 6B affinity resin. Immunohistochemical staining indicated localization of GST alpha in epithelial surface cells, underlying submucosa and smooth muscle, whereas mu and pi class isoenzymes were predominantly distributed in epithelial surface cells. These results suggest that human bladder GSTs may play an important role in providing protection against xenobiotics because epithelium is considered a target for several carcinogens and all the three classes of isoenzymes are expressed in these cells. PMID- 1888750 TI - Primary structure of molluscan metallothioneins deduced from PCR-amplified cDNA and mass spectrometry of purified proteins. AB - The primary structure of metallothioneins (MT) of a mollusc, the oyster Crassostrea virginica, was determined by molecular cloning and mass spectrometry of purified proteins. The cloning strategy included PCR amplification of the responsible cDNAs from total cDNA using completely degenerate oligonucleotides (derived from the N-terminal amino acid sequence) and oligo(dT)20 as primers. Primer extension off mRNA was used as an independent determination of the nucleotide sequence represented by the degenerate PCR primers. The deduced amino acid sequence was consistent with characteristics of class I MT. Twenty-one cysteine residues, were arranged in nine Cys-X-Cys motifs, five as Cys-Lys-Cys. A single Cys-X-X-Cys motif was also observed. Two MTs that differ only in the presence or absence of an N-acetyl group exist in this organism. Masses of tryptic peptides of purified MTs corresponded with those of peptides predicted from tryptic cleavages of the deduced amino acid sequence. Allowing for known N terminal modifications, 96% of the deduced sequence was confirmed by mass spectrometry. Comparison (FASTA algorithm) of the primary structure of the oyster MTs with those of other species indicated a higher similarity with vertebrate MTs than with those of other invertebrates. PMID- 1888751 TI - Antiarrhythmic drugs impair hepatic uptake and secretory function by different mechanisms in the isolated perfused rat liver. AB - In the present study the effect of various antiarrhythmic drugs on hepatic perfusion parameters, uptake capacity of organic anions and biliary secretion using the isolated perfused rat liver was examined. Infusion of verapamil (VP), diltiazem, N-propyl-ajmaline (NPAB), and quinidine at pharmacological doses induced consistently a 1.4-1.6-fold increase in portal pressure accompanied by a approximately 60% decrease in bile flow and a approximately 65% inhibition of biliary taurocholate (TC) excretion. Furthermore, hepatic uptake of oxygen, bromosulphthalein (BSP), and TC was significantly reduced. All these effects were dose-dependent and reversible upon withdrawal of the drugs. Studies of the hepatic circulation using a Trypan blue staining technique demonstrated a patchy perfusion pattern during infusion of the antiarrhythmic drugs as compared to the homogenously stained control organ. The hemodynamic alterations and the impairment of the hepatic initial uptake function could be entirely prevented by concomitant administration of the vasodilator papaverine. Bile flow and biliary TC excretion, however, were still inhibited under these conditions. The present results indicate that antiarrhythmic drugs produce cholestasis in the isolated perfused rat liver independently of their adverse effect on hepatic hemodynamics. PMID- 1888752 TI - Vesicles and particles of sodium bis(2-ethylhexyl) phosphate in binary and ternary systems. AB - Vesicles were identified in aqueous solution of pure sodium bis(2-ethylhexyl) phosphate, a short branched chain surfactant. Superficial tension measurements show that the vesicles appear above a molality of 0.02 (0.69 %w). These aggregates are equilibrium structures. The "packing parameter' theory established by Israelachvili et al. allows the prediction of the occurrence of such vesicles. If an organic solvent, such as xylene or ethylhexanoate, is added to the binary system, a different type of aggregate appears, the size of which is determined by several methods including electron microscopy and light scattering. Interfacial tension measurements show that these aggregates would be expected to form above a molality of 0.02. According to our experimental results, the microstructure of these aggregates can be described as micelles and/or vesicles, swollen or not. PMID- 1888753 TI - Activation and inhibition of human alcohol dehydrogenase by monoclonal antibodies. AB - The human class I alcohol dehydrogenase isozyme beta 2 beta 2 was used as the antigen to raise monoclonal antibodies. Altogether seven lines of hybridomas secreting monoclonal antibodies were obtained. None of the antibodies was isozyme specific and all of them exhibited a similar affinity against all isozymes of the human class I ADH. Five out of the seven monoclonal antibodies had no effect on beta 2 beta 2 activity. Antibody G3 acted as a non-competitive inhibitor with a KI of 3 micrograms/ml at pH 7.5. Increasing pH was effective in reducing the level of inhibition. On the other hand, antibody 1D4 exhibited a pH-dependent activation of ADH activity. In the presence of this antibody, the pH optimum of beta 2 beta 2 was shifted from 9 to 8.5 and total activity was increased by 70% at this optimal pH. Kinetic analysis indicates that 1D4 probably acts as a non competitive activator and may exert its action by interacting with the coenzyme binding site. PMID- 1888754 TI - Detergent-solubilized proteoglycans in rat testicular Sertoli cells. AB - Rat Sertoli cells were cultured for 48 h in the presence of [35S]sulfate and extracted with 4 M guanidine chloride. In this extract, a Sepharose CL-2B Kav 0.10 proteoheparan appeared lipid associated, since after addition of detergent it emerged at Kav = 0.65 on Sepharose CL-2B. Treatment of cells with 0.2% Triton X-100 released 35S-labeled material which was purified by ion-exchange chromatography and hydrophobic interaction chromatography on octyl-Sepharose. Proteoglycan with affinity for octyl-Sepharose (Kav = 0.30 and 0.12 on Sepharose CL-4B and CL-6B, respectively) mostly carried heparan sulfate chains with Kav = 0.38 and minor proportion of heparan chains with Kav = 0.77 on Sepharose CL-6B. An association with lipids was confirmed by intercalation into liposomes of this proteoheparan which might be anchored in the plasma membrane, via an hydrophobic segment and/or covalently linked to an inositol-containing phospholipid. Non hydrophobic material consisted of: (i) proteoheparan slightly smaller in size than lipophilic proteoheparan and possibly deriving from this one and (ii) two heparan sulfate glycosaminoglycan populations (Kav = 0.38 and 0.86 on Sepharose CL-6B) corresponding to single glycosaminoglycan chains and their degradation products. PMID- 1888755 TI - Isolation of two new natural pteridines from photosynthetic bacteria, Rhodopseudomonas sphaeroides. AB - Two new natural pteridines have been isolated from the cultured medium of Rhodopseudomonas sphaeroides GM-1. The compounds are tentatively identified as 2 amino-4-hydroxy-6-hydroxy-6-(1,2, 3,4-tetrahydroxybutyl)pteridine and 2-amino-4 hydroxy-6-(3-hydroxy-4-phosphonoxy-1-butenyl)pteridine by degradative experiments and by electrophoretic and paper chromatographic comparison with authentic materials. PMID- 1888756 TI - Improved purification of 12-lipoxygenase from rat basophilic leukemia cells and conditions for optimal enzyme activity. AB - 12-Lipoxygenase from rat basophilic leukemia cells was purified about 300-fold by protein-HPLC in a single run. Maximal 12-lipoxygenase activity was observed at pH 7.5, while the enzyme became almost inactive at pH 6 and 9. Although Ca2+ was not essential for 12-lipoxygenase activity, the partially purified enzyme was stimulated approx. 2-fold in the presence of 0.1-5.0 mM Ca2+. Contrary to 5 lipoxygenase from RBL-1 cells, 12-lipoxygenase was not inactivated by preincubation with Ca2+ for 1-10 min, nor was it stimulated by 0.1-10 mM ATP. PMID- 1888757 TI - Mechanism of dioxygen formation catalyzed by vanadium bromoperoxidase from Macrocystis pyrifera and Fucus distichus: steady state kinetic analysis and comparison to the mechanism of V-BrPO from Ascophyllum nodosum. AB - Vanadium bromoperoxidase (V-BrPO) catalyzes the oxidation of bromide by hydrogen peroxide, which results in the bromation of appropriate organic substrates or the formation of dioxygen, in the absence of an organic substrate and under certain other conditions. The mechanism of the bromide-assisted disproportionation of hydrogen peroxide catalyzed by V-BrPO, which is the reaction that forms dioxygen, has been investigated for V-BrPO isolated from two new marine algal sources, Macrocystis pyrifera and Fucus distichus. The steady state kinetic studies have been performed under conditions of 0.02-40 mM H2O2, 1-500 mM Br- and pH 4.0-8.0. The rate data is consistent with a substrate-inhibited bi bi ping pong mechanism, in which the substrate bromide, is also an inhibitor by a noncompetitive-type mechanism. Bromide inhibits V-BrPO from M. pyrifera most strongly at pH 5.0-5.5 and V-BrPO from F. distichus most strongly at pH 5.5-6.0. The steady state mechanism of the Macrocystis and the Fucus enzymes are compared to the mechanism of the bromide-assisted disproportionation of hydrogen peroxide catalyzed by V BrPO from Ascophyllum nodosum. In addition, the substrate hydrogen peroxide can also inhibit V-BrPO. PMID- 1888758 TI - Purification and characterization of rat ovarian 20 alpha-hydroxysteroid dehydrogenase. AB - To investigate the regulatory mechanism of 20 alpha-hydroxysteroid dehydrogenase (20 alpha-HSD) (EC 1.1.1.149) activity in ovarian tissue, the enzyme was purified from ovaries of normal mature female rats. Column chromatography of the cytosolic fraction from ovaries on DEAE-Toyopearl 650M revealed two peaks of the 20 alpha HSD activity at different ionic strengths. These peaks were designated HSD1 and HSD2, respectively. Each of the active fractions was further purified to homogeneity by dye-affinity chromatography using Matrex Green A and AF Red Toyopearl. Both the fractions appeared as a single band on sodium dodecyl sulfate polyacrylamide gel electrophoresis (at Mr = 33,000 under reducing conditions). Under non-reducing conditions, similar values were obtained on gel-exclusion HPLC, indicating that the enzyme fractions were single-stranded, monomeric polypeptides. Homogeneous HSD1 and HSD2 were purified 361-fold and 509-fold, respectively, and differed in their substrate preference. The two enzyme fractions had Km values of 4.75 microM and 5.16 microM for 20 alpha dihydroprogesterone, respectively, and showed almost the same RF values on reverse-phase HPLC and free-zone capillary electrophoresis. However, amino acid composition was slightly different, i.e. lysin content was higher in HSD1 than HSD2. Thus, it was clarified that two types of 20 alpha-HSD with very similar molecular structures are present in the rat ovary. PMID- 1888759 TI - Immunological characterisation of different meprin species in mice. AB - Meprin-a is a metalloendopeptidase present at high levels in the kidney brush border of some inbred mouse strains. Meprin-b is a latent metallo-endopeptidase, activated by trypsin-mediated proteolysis in vitro, that is present at similar activities (after activation) in all mouse strains. Meprin (a mixture of a and b forms) was purified from a high-meprin Mep-1a/a animal, and Lys-C peptides of this preparation were sequenced. The sequence data were used to direct the synthesis of peptides that were conjugated to albumin and used as immunogens. One of these antisera was specific to meprin-b and thus provided a specific tool to monitor expression of this form of meprin in different mouse strains. PMID- 1888760 TI - Isolation, characterisation and growth-related changes of an HMG-like protein from microplasmodia of Physarum polycephalum. AB - An alanine, lysine and glutamic acid-rich nuclear protein (P2) of Mr approximately 19,500 co-extracts with the histones from nuclei of Physarum polycephalum when using the CaCl2 method for histone extraction [1] and was found to have the composition previously ascribed to a putative histone H1(0) isolated from microplasmodia using 5% PCA (Yasuda, H., Mueller, R.D., Logan, K.A. and Bradbury, E.M. (1986) J. Biol. Chem. 261, 2349-2354). P2 has very similar electrophoretic properties to chicken erythrocyte histone H5, calf thymus histone H1(0) and the Physarum HMG-like protein AS-2, but does not appear to be immunologically or structurally similar to H5 or H1(0). An increase in the abundance of P2 was observed during exponential growth in microplasmodia, reaching an approximately 1:1 ratio with histone H1 by 48 h of culture. Standard amino acid analysis and NMR show that P2 is more HMG-like than H1-like and CD measurements demonstrated that P2 contains only 5% secondary structure in its maximally structured state and is, therefore, essentially unstructured under in vivo conditions. Also possible clustering of acidic residues is detected using CD and may be of functional significance. Analysis of post-translational modification of P2 shows that it is phosphorylated at up to three sites as isolated from immature spherules. The relationship of P2 to the HMG family of proteins and AS-2 is discussed. PMID- 1888761 TI - Influence of polyfluorination of the phenylalanine ring of angiotensin II on conformation and biological activity. AB - [Phe(F5)8]angiotensin II was synthesized by the solid phase method and purified by reverse-phase HPLC. In rat uterus and rabbit aorta bioassays the analogue had 10 and 50%, respectively, of the contractile activity of angiotensin II and demonstrated antagonist properties. These findings illustrate that inversion of the Phe8 ring quadrupole moment in angiotensin II decreases agonist activity and invokes antagonist properties. 1H-NMR studies at 400 MHz in DMSO-d6 demonstrated the presence of cis and trans isomers in the ratio 1:3 due to restricted rotation of the His-Pro bond. Downfield shifts of the His C2 and C4 protons in [Phe(F5)]ANG II compared to ANG II suggest that the Phe(F5) residue may be involved in a parallel-plate ring pairing interaction with the imidazole group. However heteronuclear NOE studies, carried out by measuring the proton difference spectrum before and after saturation of the fluorine resonances, showed the absence of any NOE enhancement illustrating that electrostatic influences of the Phe(F5) ring occur at relatively long range. PMID- 1888762 TI - The primary structures of four subunits of the human, high-molecular-weight proteinase, macropain (proteasome), are distinct but homologous. AB - Macropain (proteasome) is a high-molecular-weight proteinase complex composed of at least 13 electrophoretically distinct subunits. Previous work, including peptide mapping and limited amino acid sequencing, suggested that most of the subunits belong to an evolutionarily related group of different gene products (Lee et al. (1990) Biochim. Biophys. Acta. 1037, 178-185). In order to define the extent and pattern of subunit relatedness, and to determine the structural basis for possible similarities and differences in subunit functions, we are deducing the primary structures of macropain subunits by cDNA cloning and DNA sequence analysis. We report here the primary structures of four subunits. The data clearly demonstrate that the proteins represent different, but homologous gene products. Surprisingly, no evidence for homology with any other protein, including proteinases, was obtained. These results suggest that macropain is comprised of a previously unidentified family of evolutionarily related polypeptides. Because biochemical data indicate that macropain contains several different proteinase activities, the current results raise the possibility that the macropain complex is composed of a group of novel proteinases, distinct from those of other structurally identifiable proteinase families. PMID- 1888763 TI - Conformational interpretation of intramolecular electron transfer in Met5 enkephalins between Tyr and Met(S:.Br) radical. AB - Mean distances between C beta atoms of redox centers and mean values of the exponentially distance dependent rate constants for intramolecular electron transfer, (k), in aqueous solution were calculated for Met5-enkephalin and its D Ala2 analogue using the molecular mechanics and Monte Carlo techniques. The ratio of (k) values thus obtained proved similar to that determined experimentally for intramolecular electron transfer accompanying Met(S:.Br)----TyrO.radical transformation in these two peptides. This agreement indicates that the almost 2 fold difference observed between experimental k values for Met5-enkephalin and its D-Ala2 analogue can be attributed to the effect of Gly2 for D-Ala2 replacement on the average separation of the redox centers. PMID- 1888764 TI - Separation of electronic and hydrophobic effects for the papain hydrolysis of substituted N-benzoylglycine esters. AB - The role of hydrophobic and electronic effects on the kinetic constants kcat and Km for the papain hydrolysis of a series of 22 substituted N-benzoylglycine pyridyl esters was investigated. The series studied comprises a wide variety of substituents on the N-benzoyl ring, with about a 300,000-fold range in their hydrophobicities, and 2.1-fold range in their electronic Hammet constants (sigma). It was found that the variation in the log kcat and log 1/Km constants could be explained by the following quantitative-structure activity relationships (QSAR): log 1/Km = 0.40 pi 4 + 4.40 and log 1/kcat = 0.45 sigma + 0.18. The substituent constant, pi 4, is the hydrophobic parameter for the 4-N-benzoyl substituents. QSAR analysis of two smaller sets of glycine phenyl and methyl esters produced similar results. A clear separation of the substituent effects indicates that in the case of these particular esters, acylation appears to be the rate limiting catalytic step. PMID- 1888765 TI - Purification and hydrolytic action of a chitosanase from Nocardia orientalis. AB - Chitosanase from the culture filtrate of Nocardia orientalis was purified to apparent homogeneity by precipitation with ammonium sulfate followed by CM Sephadex chromatography, biospecific affinity chromatography on a Sepharose CL-4B with immobilized chitotriose and by gel filtration on Sephadex G-75. The enzyme specifically acted on chitooligosaccharides and chitosan to yield chitobiose and chitotriose as final products. The mode of action of the chitosanase on chitooligosaccharides and their corresponding alcohols suggests that the enzyme requires substrates with four or more glucosamine residues for the expression of activity and its shows maximum activity on chitohexaose and chitoheptaose. In the hydrolysis of chitosans of varying N-acetyl content, the enzyme cleaved about 30% acetylated chitosan with maximum activity and the enzyme activity decreased with increasing the degree of deacetylation of chitosans tested. The analysis of products formed from 33% acetylated chitosan shows the chitosanase is capable of cleaving between glucosamine and glucosamine or N-acetylglucosamine, but not cleaving between N-acetylglucosamine and glucosamine. On the basis of the results, the whole pathway of enymatic degradation of partially acetylated chitosan by a combination of chitosanase, exo-beta-D-glucosaminidase and beta-N acetylhexosaminidase is proposed. PMID- 1888766 TI - Chaos-theoretical analysis of possible structural quantities for globular proteins. AB - Chaos-theoretical analysis is made on possible candidates for the structural quantities. Since this is a first attempt to incorporate chaos into protein structural studies, a brief introduction to chaos especially the correlation integral method is given. It is shown that for several globular proteins the quantities called N14 and the distance rho of each C alpha atom from the center of mass suggest their deterministic origin which, we consider, is an essential requirement for a parameter to be recognized as the structural quantity. The claim made by the originator of N14 that the quantities N14 and rho can be good candidates for structural quantities is supported here by a completely new and different analysis. PMID- 1888768 TI - On the inhibition of cholinesterase by D-tubocurarine. AB - Some investigation in this laboratory pointed to an unexpectedly slow inhibition of cholinesterase by D-tubocurarine, occurring in addition to a typically instantaneous inhibition. In order to elucidate this phenomenon, the hydrolysis of butyrylthiocholine catalyzed by cholinesterase was recorded, in the absence and presence of D-tubocurarine, on a stopped-flow apparatus. Experimental results were analyzed by classical kinetic methods and by means of mathematical modeling. It was found that the inhibition is of a double character, consisting of an instantaneous phase and a slow one occurring in a minute time scale. It seems that the action of D-tubocurarine is a consequence of an instantaneous binding of D-tubocurarine to a peripheral site, followed by a relatively slow conformational transition in the enzyme. PMID- 1888767 TI - Purification and functional characterisation of the pyruvate (monocarboxylate) carrier from baker's yeast mitochondria (Saccharomyces cerevisiae). AB - Isolated yeast mitochondria were subjected to solubilization by Triton X-114 and the detergent extract was subsequently chromatrographed on dry hydroxyapatite. Purification of the yeast monocarboxylate (pyruvate) carrier was achieved by affinity chromatography on immobilized 2-cyano-4-hydroxycinnamate, as described previously for bovine heart mitochondria (Bolli, R., Nalecz K.A. and Azzi, A. (1989) J. Biol. Chem. 264 18024-18030). The final preparation contained two polypeptides of apparent molecular mass 26 and 50 kDa. The yeast carrier appeared to be less abundant, but more active, than the analogous protein from higher eukaryotes. The carrier was able to catalyse the pyruvate / pyruvate and pyruvate / acetoacetate exchange reactions, both reactions being sensitive to cyanocinnamate and its derivatives, to phenylpyruvate and to mersalyl and p chloromercuribenzoate. In the pyruvate / acetoacetate exchange reaction (200 mM internal acetoacetate, enzymatic assay), the Km value for external pyruvate was found to be 0.8 mM and the Vmax 135 mumol/min per mg protein. Among other substrates of the yeast carrier, all transported with similar affinity and identical maximal velocity against acetoacetate, we identified 2-oxoisocaproate, 2-oxoisovalerate and 2-oxo-3-methylvalerate. Lactate was not translocated by this carrier with a measurable rate, neither were di- or tricarboxylates. PMID- 1888769 TI - Lecithin-cholesterol acyltransferase in the metabolism of high-density lipoproteins. PMID- 1888770 TI - Kinetic control of steroidogenesis by steroid concentration in guinea pig adrenal microsomes. AB - For clarification of the effects of steroid concentration on steroidogenesis of adrenal microsomes, the kinetic parameters, Km and kcat, were determined in the steady-state for progesterone and 17 alpha-hydroxyprogesterone metabolism catalyzed by P-450C21 and P-450(17 alpha lyase) in guinea pig adrenal microsomes. At a high concentration of progesterone, it was equally metabolized by P-450C21 and P-450(17 alpha lyase), while at a low concentration, it was hydroxylated at 17 alpha-position with twice higher rate than at 21-position. 17 alpha Hydroxyprogesterone is apparently metabolized preferentially by P-450C21 at any concentration. Although the productions of deoxycortisol and androstenedione from 17 alpha-hydroxyprogesterone were strongly inhibited by progesterone, androstenedione formation from progesterone was not inhibited by a high concentration of progesterone. The addition of liposomal P-450C21 to the reaction medium containing adrenal microsomes caused a decrease in the concentration of 17 alpha-hydroxyprogesterone released into the medium in the steady state reaction, but this had no effect on the activity of androstenedione formation from high concentrations of progesterone. It thus follows that androstenedione is produced by successive monooxygenase reactions without the release of 17 alpha hydroxyprogesterone from P-450(17 alpha lyase) at a high concentration of progesterone, which is the condition of the adrenal microsomes in vivo. PMID- 1888771 TI - Effect of indomethacin on the uptake, metabolism and excretion of 3-oxocholic acid: studies in isolated hepatocytes and perfused rat liver. AB - 3 alpha-Hydroxysteroid dehydrogenase catalyzes the reduction of 3-oxo-bile acids and binds 3 alpha-hydroxy bile acids. Indomethacin is a competitive inhibitor of the enzyme. In incubations of isolated rat hepatocytes, indomethacin delayed the intracellular reduction and the initial uptake of 3-oxocholic acid. Following a tracer dose of 3-oxocholic acid in perfused rat liver, rapid biliary excretion was observed mainly as taurocholic acid. Only 1.1% of the dose was recovered in the caval outflow and nearly all appeared in the first 5 min collection. When the tracer dose was given after initiating a constant infusion of indomethacin (50 microM), a dramatic decrease in biliary excretion was observed, still mainly as taurocholic acid, and 14% of the dose was recovered in the caval effluent: 10% in the first 5 min collection, mainly as 3-oxocholic acid, followed by a steady, slow release of mainly taurocholic acid. The increased intrahepatic retention of bile acids and slow release into perfusate and bile in response to indomethacin are consistent with displacement of bile acids from cytosolic protein. PMID- 1888772 TI - The effect of n-3 fatty acids on osmotic fragility of rat erythrocytes. AB - In order to study the effect of n-3 fatty acids on the physical state of the erythrocyte membrane, measured as osmotic fragility, rats were fed a diet supplemented in n-3 fatty acids (1.5 ml/day, 35% 20:5, 30% 22:6) for 21 days. With salt concentrations ranging from 0.37% to 0.44%, osmotic resistance was increased by 25% to 45% in cells from n-3-fed animals compared to controls. No change was observed in either phospholipid or cholesterol content in the membrane. A small, but still significant difference (P less than 0.05) in phospholipid sub-class distribution was observed in that the phosphatidylethanolamine fraction was decreased and the phosphatidylserine fraction increased after n-3 supplementation. The major change was, however, that the level of eicosapentaenoic acid (20:5(n-3] in phospholipids was increased from 1.5% of total fatty acids to 4.5%. This increase was mainly at the expense of linoleic acid (18:2(n-6]. No change was observed in the level of docosahexaenoic acid (22:6(n-3]. It is thus concluded that both the fatty acid composition and the nature of the phospholipid polar head group may influence the osmotic fragility of erythrocytes. PMID- 1888773 TI - Delta 5-desaturation of dihomogammalinolenic acid (20:3(n-6)) into arachidonic acid (20:4(n-6)) by rat liver microsomes and incorporation of fatty acids in microsome phospholipids. AB - Liver microsomes of rats fed an essential fatty acid (EFA)-deficient diet or a commercial balanced diet were used to study the effect of incubation time on the delta 5-desaturation of [14C]dihomogammalinolenic acid (20:3(n-6)) into arachidonic acid (20:4(n-6)) and incorporation of the two acids into microsomal phospholipids. The EFA-deficient diet highly increased the desaturation rate of 20:3(n-6). Incorporation of the formed 20:4(n-6) into microsomal phospholipids was also increased but at saturating concentration of substrate only. At early times of incubation, the precursor 20:3(n-6) was rapidly incorporated into phospholipids. Formation and incorporation of 20:4(n-6) into phospholipids proceeded more progressively. Data suggest that desaturation of 20:3(n-6) and incorporation of both 20:3(n-6) and 20:4(n-6) into phospholipids occur concomitantly and independently. PMID- 1888774 TI - UVA-induced lipid peroxidation in cultured human fibroblasts. AB - The UVA irradiation of cultured human fibroblasts leads to the formation and to the release of thiobarbituric acid-reactive substances in the supernatant. The major thiobarbituric acid-reactive substance is identified by fluorescence spectroscopy and HPLC, as malondialdehyde or malondialdehyde-forming substances under the thiobarbituric acid assay conditions. Malondialdehyde formation strongly suggests a UVA-induced lipid peroxidation. Lipid peroxidation is also supported by the inhibitory effect of D,L-alpha-tocopherol, the well-known chain breaking antioxidant, by the additional malondialdehyde formation in the dark after the photooxidative stress and by membrane damage revealed by lactate dehydrogenase leakage. PMID- 1888775 TI - Synthesis of phosphatidylinositol in rat liver microsomes is accompanied by the rapid formation of lysophosphatidylinositol. AB - In mammalian cells, newly synthesized phosphatidylinositol (PI) has a fatty acid composition similar to its precursors, phosphatidic acid and CDP-diacylglycerol (DAG). It is then remodelled by deacylation/reacylation cycles to the predominant form, 1-stearoyl, 2-arachidonoyl PI. Incubation of dipalmitoyl CDP-DAG, [3H]inositol and Mg2+ with rat liver microsomes results in the rapid synthesis of PI, along with the simultaneous formation of multiple species of lysoPI. Analysis of the kinetics of formation of PI and lysoPI reveals no lag in the formation of lysoPI from PI. Moreover, evaluation of the concentration dependencies indicate nearly identical apparent Km values for PI synthesis compared with lysoPI synthesis for the substrates inositol (180 microM) and CDP-DAG (100 microM). The dependence on pH and the requirement for Mg2+ or Mn2+ are nearly identical for PI and lysoPI formation and the labelling of both lipids is similarly inhibited by submicromolar concentrations of calcium and by NEM. These results suggest that the formation of lysoPI is dependent on the initial, rate-limiting synthesis of PI. Pulse-chase analysis of the labelling of these lipids indicates that PI and lysoPI rapidly equilibrate after the initial slow synthesis of PI. In addition, it appears that only newly synthesized PI is involved in lysoPI formation. The extent of lysoPI formation depends upon the fatty acid composition of the added CDP-DAG. A number of experimental approaches demonstrate that lysoPI is not formed when pre-existing microsomal PI is labelled by head group exchange, perhaps because this PI has already undergone remodelling to polyenoic forms. These data suggest that the rapid deacylation of newly synthesized PI may represent the first step in PI remodeling. PMID- 1888776 TI - Fatty acid remodelling of phosphatidylinositol under conditions of de novo synthesis in rat liver microsomes. AB - Phosphatidylinositol (PI) is initially synthesized in mammalian cells with a fatty acid composition similar to that of its precursor, primarily monounsaturated forms of cytidine diphosphodiglyceride (CDP-DAG). However, at the steady state, over 80% of PI exists in the 1-stearoyl, 2-arachidonoyl form. The fatty acid remodelling of PI is due to a number of deacylation/reacylation mechanisms. In the preceding paper we demonstrated that de novo synthesized PI is rapidly deacylated and subsequently reacylated. In this report we present further evidence that cycles of deacylation and reacylation are involved in the remodelling of PI. Incubation of microsomes with CDP-DAG of different fatty acid composition results in quantitative and qualitative differences in lysoPI formation. Additionally, analyses of the resulting lysoPI and PI species reveal that multiple species of fatty acids are incorporated into the 1-position of both PI and lysoPI. Addition of acylation cofactors (fatty acyl CoAs or ATP plus CoA) potentiate reacylation in this system. The addition of stearoyl or myristoyl CoA during de novo synthesis of PI results in the incorporation of these added fatty acids into the I-positive of PI. In addition, some evidence is presented that multiple mechanisms for remodelling of the 1-position of PI may be active in the microsomes, including ATP- and CoA-dependent acylation, ATP-independent, CoA dependent acylation and CoA-independent mechanisms. Finally, the disappearance of only a subset of lysoPI species upon the addition of acylation cofactors suggests that the reacylation step exhibits some substrate specificity. PMID- 1888777 TI - Coenzyme A-dependent, ATP-independent acylation of 2-acyl lysophosphatidylinositol in rat liver microsomes. AB - Phosphatidylinositol (PI) is synthesized from cytidine-diphosphodiacylglycerol (CDP-DAG) and inositol by the enzyme PI synthase. CDP-DAG is itself synthesized from phosphatidic acid and CTP. The observation that PI differs in fatty acid composition from its precursors CDP-DAG and phosphatidic acid led to the proposal that following its synthesis the fatty acids of PI are removed and replaced by others in a process called fatty acid remodelling. Previously, we used rat liver microsomes to study the molecular mechanisms of PI remodelling. Following its synthesis, PI is rapidly deacylated to form lysoPI which is reacylated to form new PI species. PI remodelling occurs predominantly at the 1-position. We demonstrate here that lysoPI can be acylated in the 1-position in an ATP independent manner. The acylation of 2-acyl lysoPI by the coenzyme A-dependent, ATP-independent mechanism was examined. The acylation exhibits a pH optimum of 7.5, does not require a divalent cation, and is not inhibited by Ca2+ or Mg2+, although Zn2+ is a potent inhibitor. The apparent Km values for coenzyme A and 2 acyl lysoPI are 14 microM and 30 microM, respectively. The acylation of 2-acyl lysoPI incorporates primarily stearic acid into the 1-position of PI, as would be expected based on the fatty acid composition of steady-state PI in rat hepatocytes. PMID- 1888778 TI - Effect of estrogen and progesterone on the hepatic cholesterol 7-alpha hydroxylase activity in ovariectomized baboons. AB - Cholesterol 7 alpha-hydroxylase activity was measured in livers from ovariectomized baboons fed a high cholesterol high saturated fat diet and maintained in four groups: untreated controls, estrogen (100 micrograms/g per week), progesterone (3 mg/kg per day) and estrogen + progesterone. Estrogen treatment alone increased hepatic 7 alpha-hydroxylase activity by 2.7-fold, whereas progesterone treatment alone did not influence hepatic 7 alpha hydroxylase activity. The increase in 7 alpha-hydroxylase activity in estrogen + progesterone group was similar to that in the estrogen group. PMID- 1888779 TI - Lipoxin formation in fish leucocytes. AB - Adherent leucocytes, consisting of mainly macrophages, isolated from the haemopoietic head kidney of five species of fish were challenged with calcium ionophore and the resulting lipoxygenase products were separated and identified by reverse-phase high performance liquid chromatography. Of the fish examined, only adherent leucocytes from the Atlantic salmon and mirror carp generated lipoxins. Atlantic salmon leucocytes synthesized mainly lipoxin (LX) A4/LXA5 and 11-trans-LXA4/11-trans-LXA5, while mirror carp produced both LXA4 and LXB4 and their isomers but no 5-series lipoxins. This variation in lipoxin generation suggests that there are differences in the mode(s) of biosynthesis of these compounds between the two species of fish. PMID- 1888780 TI - Readily synthesized calibration compounds for quadrupole and magnetic instruments for use over the mass range to 2000 daltons. AB - Volatile mass calibration standards have been prepared by esterifying beta cellobiose (4-beta-D-glucopyranosyl-D-glucose) with a mixture of heptafluorobutyric (HFB) anhydride and pentafluoropropionic (PFP) anhydride. The mixed esters produce spectra that are useful for mass spectrometer calibration with positive or negative ion methane chemical ionization and electron impact over the mass range 300-2000. The spectra contain prominent ions spaced at m/z 20 and m/z 50 intervals. Using the mixed ester with direct insertion probe introduction gives intense spectra that persist for tens of minutes. All signals above m/z 194 derived from these substances disappear rapidly upon withdrawal of the probe. The composition and exact masses are given for the positive and negative ion spectra of a mixed HFB/PFP ester of beta-cellobiose. Two other calibrants are described: one made from beta-cellobiose using a mixture of HFB, PFP and trifluoroacetic anhydrides, and another the HFB/PFP mixed ester of perseitol. These are examples of the flexibility of this approach with respect to mass range and ion composition. PMID- 1888781 TI - Sequencing of peptides containing alanine, asparagine, histidine, isoleucine and tryptophan by partial methanolysis and fast atom bombardment mass spectrometry. AB - Five peptides containing the amino acids alanine, asparagine, histidine, isoleucine and tryptophan were investigated by partial methanolysis and fast atom bombardment mass spectrometry in order to examine the behaviour of these amino acid residues under the conditions employed in the methanolytic step. The results obtained confirm that partial methanolysis prior to mass analysis increases considerably the content of sequence information in the mass spectra and that no secondary reactions occur in the residues of the amino acids now investigated, with the exception of the esterification of the glutamic acid carboxyl group and partial conversion of the asparagine amide group in the corresponding methyl ester. PMID- 1888782 TI - Quantification of plasma phenylethylamine by combined gas chromatography/electron capture negative ion mass spectrometry of the N-acetyl-N-pentafluorobenzoyl derivative. AB - An ultrasensitive method capable of detection and quantification of beta phenylethylamine in 1 ml of human plasma has been developed using gas chromatography/electron capture negative ion mass spectrometry. Phenylethylamine and tetra-deutero phenylethylamine internal standard in plasma were acetylated, extracted into organic solvent and then further acylated with pentafluorobenzoyl chloride. The N-acetyl-N-pentafluorobenzoyl-phenylethylamines were detected by high-resolution single ion monitoring of the molecular ions. Normal plasma levels were found to be 41.5 +/- 10.7 pg ml-1, in accordance with results of a previous high-performance liquid chromatographic method. PMID- 1888783 TI - Identification and determination of propafenone and its principal metabolites in human urine using capillary gas chromatography/mass spectrometry. AB - The capillary gas chromatography/mass spectrometry of trimethylsilyl trifluoroacetyl, trifluoroacetyl and pentafluoropropionyl (PFP) derivatives of the antiarrhythmic agent propafenone (Rytmonorm), as well as its main metabolites N-despropyl-propafenone and 5-hydroxy-propafenone, have been investigated. Both electron impact and positive isobutane chemical ionization mass spectrometry using the Ion Trap Detector have been evaluated. The presence of propafenone and its co-extracted metabolites in human urine at time intervals after the oral administration of 150 mg Rytmonorm to healthy volunteers was established, and the urinary excretion of propafenone and 5-hydroxy-propafenone was calculated using selective chemical ionization mass spectrometric detection. Only a few per cent of the dose was excreted unchanged in the urine. Large intersubject variabilities had been observed also. The large dynamic range of the Ion Trap Detector and the high correlation coefficients (0.92-0.99) of the calibration curves were striking. PMID- 1888784 TI - CRNAs, whose team are we on? PMID- 1888785 TI - Point/counterpoint. The anesthesia care team. PMID- 1888786 TI - Effect of transport time and FiO2 on SpO2 during transport from the OR to the PACU. AB - Early postoperative hypoxemia may be due to a reduced functional residual capacity, hypoventilation, and ventilation-perfusion mismatch. These factors reduce the partial pressure of the arterial oxygen which ultimately reduces the oxygen transported to the tissues by decreasing the hemoglobin saturation. This may lead to cellular ischemia and death. Oxygen saturation may decrease during transport from the operating room to the postanesthesia care unit. The length of transport time in large operating suites may exceed 5 minutes, which may lead to inadequate oxygenation. This research used a pretest-posttest control group design on a convenience sample. Subjects were randomized into either the treatment or control group. At emergence, the SpO2 measured and the stopwatch started. The treatment group received 40% oxygen via a venturi mask during transport while the control group breathed room air. After a routine transport to the postanesthesia care unit, the SpO2 was again measured and the transport time was recorded. Oxygen saturation was found to be significantly greater in the group breathing supplemental O2 during transport. PMID- 1888787 TI - Does the administration of oral Bicitra before elective cesarean section affect the incidence of nausea and vomiting in the parturient? AB - Soluble oral antacids are commonly used before anesthesia for cesarean section. The purpose of this prospective, single institution, randomized experimental study was to examine the relationship of oral administration of Bicitra (sodium citrate and citric acid) to the incidence of nausea and vomiting in patients undergoing elective cesarean section utilizing regional anesthesia, and to evaluate its effectiveness in neutralizing gastric acid. Eighty-six patients were studied (39 in a control group and 47 in a Bicitra treatment group) to ascertain if there was any difference with regard to height, weight, parity, gravity, age, race, incidence of heartburn with pregnancy, incidence of nausea with pregnancy, length of NPO status, preoperative systolic blood pressure (SBP), perioperative low level of SBP, and cumulative drop in SBP. Pearson chi square analysis showed no significant difference between the two groups for all variables or the incidence of nausea and vomiting. No significant difference was noted in the mean pH and volume of emesis of seven subjects analyzed using pooled t tests. After initial hypothesis testing was concluded, the sample was divided into two groups, those who experienced nausea and those who were free from nausea. The nausea group demonstrated a significantly greater cumulative decrease in SBP than did the non-nausea group. Larger patients (mean cube root weight index of 2.78) tended to become nauseated more frequently. PMID- 1888789 TI - The Nursing Pain Association. PMID- 1888788 TI - Determination of power and sample size for a statistical test. PMID- 1888790 TI - Functional requirements of c-myb during normal and leukemic hematopoiesis. PMID- 1888791 TI - Molecular genetics of the retinoblastoma suppressor gene. AB - The retinoblastoma gene (RB) is the prototype of a class of genes, called tumor suppressor genes, for which loss-of-function mutations are oncogenic. Such genes would then normally function to suppress or prevent tumor formation. Classical genetic and cytogenetic studies of retinoblastoma, a rare childhood eye cancer, laid a fundamental groundwork for the molecular cloning of this gene. Surprisingly, mutations of RB are found not only in retinoblastomas but also in some osteosarcomas, soft-tissue sarcomas, and carcinomas of breast, lung, prostate or bladder, suggesting a broad role for RB in human oncogenesis. In support of this hypothesis, a wild-type copy of RB is able to suppress the neoplastic properties of several types of tumor cells with mutated endogenous RB alleles. The RB gene product, pp110RB, is a nuclear phosphoprotein with DNA binding activity. RB protein is cyclically phosphorylated and dephosphorylated during the cell division cycle, and may play a significant role in its regulation. PMID- 1888792 TI - Capsules for frozen sectioning of small specimens. AB - It was necessary to make sections of small unfixed specimens which had been frozen while still immersed in their normal culture medium. The principal difficulty stemmed from the poor sectioning quality of the frozen culture medium. A capsule is described which has a narrow well in which the tissue specimen fits snugly within a small amount of culture medium. After freezing, the whole capsule is sectioned and the resulting sections, being nearly devoid of culture medium, are of good quality. PMID- 1888793 TI - Citric acid-ammonium acetate buffer. AB - A pH table is reported for citric acid-ammonium acetate buffers that are useful for horseradish peroxidase (HRP) histochemistry. PMID- 1888794 TI - The importance of choice of visualization technique in the use of indirect immunodetection methods: specific reference to the detection of light chain movement on a regulatory myosin. AB - This paper addresses a practical problem associated with the use of visual detection systems used in immunoblotting. Western blot analyses from the same experiment, differing only at the level of the secondary antibody used and the means of visualization employed, have produced apparently different results which, in isolation, could lead to different conclusions at both the qualitative and quantitative level. Indirect immunofluorescence, using a fluorescein isothiocyanate labeled secondary antibody and visualized by fluorescence excitation, was excellent for detecting the major species present but could not detect minor components. Indirect immunoperoxidase staining, on the other hand, appeared to detect all immunoreactive species present, both major and minor, presumably reflecting a more realistic picture of the experimental situation. All results were obtained during the observation of photocross-link formation between regulatory light chains and regulatory and essential light chains after hybridization of scallop myosin with benzophenone-4-maleimide labeled regulatory light chains. Results were obtained under conditions designed to simulate the physiological states of rest and rigor; the implication of these results with respect to myosin-linked regulation is discussed. PMID- 1888795 TI - A quick embedding method for light and electron microscopy of textile fibers. AB - A quick embedding method employing UV polymerization reactions has been devised for embedding fibers in acrylic and methacrylate media. The resultant thin, flat embeddings are suitable for both light and electron microscopy. PMID- 1888796 TI - Reference markers in serial sections. AB - A simple technique for placing reference markers on serial sections is presented. The objective is to permit proper cut orientation, especially when the shape of a structure appearing in the various cuts is to be digitized for computer analysis. PMID- 1888797 TI - Hardware for in-flight fixation of plants in microgravity. AB - NASA-approved hardware was designed for an experiment involving in-flight fixation of 4.8-day-old seedlings of Brassica perviridis. The hardware is inexpensive, reliable, and simple to construct. This hardware aboard flight 61-C of space shuttle Columbia functioned perfectly, and required less than 0.5 hr of crew time for training. Analyses of cellular ultrastructure indicated excellent ultrastructural preservation. PMID- 1888798 TI - Measurement of tissue lithium concentration by lithium magnetic resonance spectroscopy in patients with bipolar disorder. AB - Measurements of the lithium concentration in the occipital pole of the head and calf muscle of nine patients with bipolar disorder in remission were performed using in vivo lithium-7 nuclear magnetic resonance spectroscopy (7Li NMR). 7Li NMR measurements were performed on a 1-m-bore, 1.85-T, superconducting magnet supplemented with a multinuclear spectrometer, using 11.5-cm-diameter surface coils. The average lithium concentration in the occipital pole was 0.36 +/- 0.10 mEq/L, whereas in the muscle it was 0.50 +/- 0.17 mEq/L, both lower than the average serum lithium concentration (0.79 +/- 0.23 mEq/L). The average brain/serum lithium concentration ratio was 0.47 +/- 0.12 whereas the average muscle/serum lithium concentration ratio was 0.66 +/- 0.20. There was a positive correlation between the brain versus serum and brain versus muscle lithium concentrations. The hypothesis is advanced that the minimal effective concentration of brain lithium concentration for maintenance treatment of bipolar disorder is around 0.2-0.3 mEq/L. PMID- 1888799 TI - Erythrocyte choline concentration in bipolar disorder: a predictor of clinical course and medication response. AB - Erythrocyte choline concentrations were measured in hospitalized patients with bipolar disorder, manic phase, and control subjects. There was a significant elevation in mean erythrocyte choline in the patients with mania. This elevation in erythrocyte choline was due to a subgroup of patients with especially high values. Significant clinical differences were apparent between the patients with "high" and those with "low" erythrocyte choline concentrations. The subgroup of manic patients with elevated erythrocyte choline had a more severe illness at admission, a worse outcome at discharge, and required significantly more neuroleptic during hospitalization than their low choline counterparts; that is, they were less likely to respond well to lithium alone. Furthermore, the bipolar patients with low erythrocyte choline concentrations, as a whole, had more than four times as many previous manic episodes than depressive episodes, while the patients with high choline values had approximately the same number of past manias and depressions. These results are discussed in light of the evidence implicating cholinergic neurotransmission in the pathophysiology of affective disorders. In addition, the design of future clinical studies of erythrocyte choline and its possible clinical utility are discussed. PMID- 1888800 TI - PET in generalized anxiety disorder. AB - Positron emission tomography (PET) measurements of cerebral glucose use were made in 18 patients with generalized anxiety disorder (GAD) during a passive viewing task off medication, and an active vigilance viewing task before and after medication or placebo treatment. In the passive viewing task, patients with GAD were compared with 15 normal controls. A significant difference in pattern of absolute brain metabolism was found. Patients showed lower absolute metabolic rates in basal ganglia and white matter. Relative metabolism was increased in the left inferior area 17 in the occipital lobe, right posterior temporal lobe, and the right precentral frontal gyrus. Significant left-right asymmetry of the parahippocampal gyri was not found in patients with GAD. An active vigilance task resulted in activation of relative basal ganglia metabolism in patients. Benzodiazepine therapy resulted in decreases in absolute metabolic rates for cortical surface, limbic system, and basal ganglia and was not associated with normalization of patterns of glucose metabolism. Change in anxiety scores was significantly correlated with change in limbic system and basal ganglia for the placebo group. The normal-anxious difference in the basal ganglia and the change seen in this region after benzodiazepine treatment are suggestive of a role in anxiety for this structure. PMID- 1888801 TI - Effects of imipramine on the nocturnal behavior of bilateral olfactory bulbectomized rats. AB - Experiments were performed to characterize the circadian behavior of bilateral olfactory bulbectomized (OB) rats and to investigate the effects of imipramine on that behavior. OB and sham-operated (SO) rats were housed individually for 2 weeks in activity monitors on a 13-hr light/11-hr dark cycle. OB rats were significantly more active than SO rats during the dark phase of the cycle, and both groups of rats were equally inactive during the light phase. Seven daily injections of imipramine [10.0 mg/kg, intraperitoneally (IP)] significantly reduced the nocturnal activity of OB rats, such that OB rats displayed nocturnal activity equivalent to SO rats. Abnormally high nocturnal activity is another important characteristic of the OB rat. This behavioral characteristic may prove to be valuable for the evaluation of novel antidepressive compounds. PMID- 1888802 TI - The QKd interval in panic disorder: an assessment of end-organ thyroid hormone responsivity. AB - The QKd interval was utilized as a presumptive index of end-organ thyroid hormone effect to test the hypothesis that patients with panic disorder might have abnormal tissue-level responsivity to normal levels of peripherally circulating thyroid hormones. No significant differences in QKd intervals were found between 15 patients with panic disorder (230 +/- 50 msec) and 20 normal controls (224 +/- 29 msec) while drug-free. These findings suggest that patients with panic disorder have normal tissue-level responsivity to thyroid hormone. PMID- 1888803 TI - Prevalence and severity of akathisia in patients on clozapine. AB - The atypical antipsychotic clozapine is reported to have unique therapeutic effects and to produce minimal extrapyramidal side effects. However, in a blind survey, akathisia was observed to be similar in prevalence and severity in patients treated with clozapine and those receiving standard neuroleptic antipsychotic drugs. In addition, as with standard antipsychotic drugs, the presence of akathisia in patients receiving clozapine was associated with a worse overall clinical outcome. The results suggest that akathisia may be a common side effect of all antipsychotic drugs, that akathisia may be produced by a mechanism distinct from other locomotor effects of these medications, and that patients receiving clozapine, like patients receiving standard antipsychotic drugs, should be monitored for akathisia. PMID- 1888804 TI - Fibrinolytic behaviour of streptokinase-immobilized poly(methacrylic acid-g ethylene oxide). AB - Streptokinase was immobilized on poly(methacrylic acid-g-ethylene oxide) surfaces by means of a modified coupling reagent method. The surfaces were activated with a carbodiimide to form an O-acyl isourea derivative, which, upon addition of the enzyme, condensed to form the corresponding amide. The quantity of enzyme immobilized on the surface increased as the reaction time with carbodiimide and streptokinase increased. The fibrinolytic activity of the immobilized enzyme systems was measured by a clot lysis assay. The dynamics of fibrin clot lysis was investigated for a period of up to 500 min. The lysis reaction mechanism was found to approximate a first-order fibrin degradation. In addition, the kinetic rate constant was found to increase with increasing immobilized enzyme content. PMID- 1888805 TI - Ellipsometric studies of plasma protein adsorption on membrane polymers for blood purification. AB - Description of ellipsometric studies on absorption of the human plasma proteins; albumin (HSA), immunoglobulin G (IgG) and fibrinogen (FGN) to polymer surfaces of polyamide, polysulphone, polyetherpolycarbonate and polyacrylonitrile copolymer. Thin layers of the polymers (20-30 nm) were cast onto silicon dioxide/silicon wafers by a spin-coating procedure. The variations observed in surface concentration and adsorption time of the proteins were significant in all four polymers investigated. PMID- 1888806 TI - Microcapsules through polymer complexation. I: Complex coacervation of polymers containing a high charge density. AB - Acidic and basic methacrylate co- and ter-polymers based on (respectively) methacrylic acid (MAA) and dimethylaminoethyl methacrylate (DMAEMA) were prepared by solution free radical polymerization and structurally characterized by NMR spectroscopy and dilute solution viscometry. Relationships between pKa/pKb/pH, solubility and extent of ionization were determined by acid/base titration. Yields and equilibrium water contents of complex coacervates from these polymers were measured, and microcapsule forming systems based on this effect were developed as potential prostheses for organ transplantation. Short term cell viability in these capsules was demonstrated using erythrocytes as a model cell line. PMID- 1888807 TI - Texturing of polymer surfaces at the cellular level. AB - A technique to surface-texture polymer sheets with any conceivable surface morphology is described. It uses technology developed for semiconductor device fabrication. It allows the definition and control of implant surface texture at subcellular levels, down to 2 micron dimensions, and the cellular response to those textures to be studied in vitro and in vivo. The results of a pilot study are presented and the biological significance of a microscopic surface texture is discussed. PMID- 1888808 TI - Synthesis and antithrombogenicity of heparinized polyurethanes with intervening spacer chains of various kinds. AB - Heparin was immobilized to polyetherurethaneurea membrane by covalent or ionic bondings with intervening spacer chains having different lengths and different terminal functional groups. The amount of immobilization of heparin and the release rate of immobilized heparin were controlled by the nature and the mode of bonding of spacer chains. The heparinized polyetherurethaneurea membranes became more in vitro antithrombogenic and suppressed more strongly the adhesion and activation of platelets, as the amount of immobilization increased. It was also shown that the membrane to which the low-molecular-weight fraction of heparin was immobilized was less stimulating to platelets. PMID- 1888809 TI - Development of a new in vitro model for studying implantable polyurethane calcification. AB - The objective of this study was to reproduce mineralization of polymeric substrate in an extracirculatory environment which would facilitate investigation of the calcification mechanism in implantable biomaterials and methods of prevention. Calcification was examined on polyurethane films incubated in metastable solutions of calcium phosphate and the role of strain, serum and polymer porosity was examined. Validation of the model was evaluated by examining the calcification of both highly calcifiable biomaterial (bioprosthetic tissue) and a non-calcifiable biomaterial (charge-modified tissue and polyurethane containing anticalcification agent). It is concluded that the developed model is adequately sensitive to diagnose biomaterials' propensity to calcify and could serve as a pre-screening method to examine calcification mechanism and methods of prevention. PMID- 1888810 TI - Bonding osteogenesis in coralline hydroxyapatite combined with bone marrow cells. AB - Coralline hydroxyapatite ceramics alone (control) and the ceramics combined with rat marrow cells were implanted subcutaneously in the backs of syngeneic Fischer rats and harvested at 1,2,3,4,6,8 and 24 wk after surgery. None of the control ceramics (without marrow) showed bone formation. However, ceramics combined with marrow cells showed consistent new bone formation in the pore regions. Histometrical results revealed increased new bone formation over time. Undecalcified sections of the ceramics studied by fluorochrome labelling showed that the osteogenesis began directly on the surface of the ceramic and proceeded centripetally towards the centre of the pores (bonding osteogenesis). SEM-EPMA analysis of the bone-ceramic interface also revealed direct bonding of bone to the ceramic surface. PMID- 1888811 TI - Scanning electron microscopy of platinum scala tympani electrodes following chronic stimulation in patients. AB - Platinum (Pt) electrodes from three auditory prostheses (Cochlear Pty Ltd) were examined for evidence of corrosion following implantation periods of up to 1000 days. These devices were used for periods ranging from 1600 to 10,400 h and developed maximum charge densities of 0.257 microC mm-2 geom. per phase. Scanning electron microscopy of the surface of the 66 stimulated electrodes examined showed no evidence of definitive Pt corrosion. Their surface features were essentially identical to control (unstimulated) electrodes. In addition, there was no evidence of any change in the surface morphology of the Silastic carrier adjacent to the stimulating electrodes. These results indicate that Pt is a suitable electrode material for neural prostheses that use relatively large surface area electrodes (0.1-1.0 mm2) and low to moderate charge densities (0.01 0.26 microC mm-2 geom. per phase). PMID- 1888812 TI - Effects of environmental exposure on carbon polysulphone composites. AB - In vivo and in vitro studies were designed to characterize the material degradation associated with implantation of carbon fibre-reinforced polysulphone (C/PS). Composite plates were compression moulded for both studies, and a fibre orientation of 0 degrees with the long axis and a fibre volume fraction of approximately 55% were used. The in vitro experiment involved soaking three groups of four plates each at 4, 12 and 26 wk in 0.9% saline solution at 37 degrees C. The plates were measured for weight gain after each time period and mechanically tested non-destructively in four-point bending to determine modulus. The in vivo experiment involved implanting three groups of eight composite plates (24 total) subcutaneously in the abdomens of 12 rabbits (two implants/animal). Implants were harvested at 4, 12 and 26 wk after implantation and evaluated for changes in weight or modulus of elasticity. In vitro results showed a statistically significant (P less than 0.05 paired t-test) increase in weight for all time periods: 0.41, 1.25 and 0.93% weight gain for the 4, 12 and 26 wk periods respectively. In vivo results were similar to those in vitro: 0.66, 1.06 and 1.15% weight gain for the 4, 12 and 26 wk periods respectively (P less than 0.05 paired t-test). There was no statistically significant difference between the pre- and post-implantation modulus of elasticity for any time period in vivo or in vitro. However, in both studies, on average, the modulus tended to increase with environmental exposure. PMID- 1888813 TI - Evaluation of the mechanical properties of hot isostatically pressed titania and titania-calcium phosphate composites. AB - A number of composites based on titania and calcium phosphates, hydroxyapatite, bone ash or beta-tricalcium phosphate, were sintered by glass-encapsulated hot isostatic pressing at 925 degrees C. The mechanical properties of the titania and titania-calcium phosphate composites--three-point bending strength, fracture toughness and Young's modulus--were 250-450 MPa, 2.5-2.9 MPa m1/2 and 230-270 GPa, respectively. Hardness and density were also measured. The results suggest that these composites have potential applications in medicine as implant materials. PMID- 1888814 TI - Review article: stomach wars--a mucosal defense initiative. AB - A model is presented which attempts to unify many of the processes identified in recent years as contributing to the maintenance of mucosal integrity in the stomach. Two concepts, namely acid disposal and rapid repair of superficial injury, are highlighted as being of particular physiological significance. The mechanisms involved in protection of the normal mucosa against luminal aggressors (e.g. acid/pepsin, ethanol, aspirin) must be distinguished from the factors which influence the healing of a pre-existent ulcer. In this context, the relatively neglected topic of wound healing in the gastric mucosa is considered, and the implications for current therapeutic strategies and for the discovery of new anti ulcer drugs are explored. PMID- 1888815 TI - Colloidal bismuth subcitrate causes sustained release of gastric mucosal prostaglandin E2. AB - Gastric application of high doses of colloidal bismuth subcitrate (CBS) stimulates mucosal prostaglandin E2 (PGE2) production, which is considered part of the mechanism by which the drug accelerates peptic ulcer healing. Whether therapeutic, orally administered, doses of CBS cause a sustained stimulation of prostaglandin production is not known. We have, therefore, determined gastric luminal release of PGE2 during 'steady-state' perfusion of the stomach with CBS (10 mg/ml; isotonic mannitol 5 ml/min) and 4 h after the last oral dose of the drug (240 mg b.d.) for 2 weeks (isotonic mannitol 5 ml/min) in 8 healthy volunteers. A significant increase in PGE2 concentrations (712 (409-1076) vs. control 334 (252-655) pg/ml; medians with Q50 ranges; P less than 0.02) and PGE2 output (12.5 (7.3-14.3) vs. control 4.8 (4.1-7.3) ng/15 min; P less than 0.02) occurred during gastric perfusion with CBS. A similar increase in PGE2 concentrations (630 (297-1429) pg/ml; P less than 0.02) and PGE2 output (12.6 (6.4-22.2) ng/15 min; P less than 0.02) was observed following treatment with CBS for 2 weeks. These results suggest that therapeutic doses of CBS cause a sustained stimulation of gastric mucosal PGE2 formation. PMID- 1888816 TI - The effects of renzapride, a novel prokinetic agent, in diabetic gastroparesis. AB - Gastric emptying was measured in 9 diabetic patients with autonomic neuropathy (Group 1) and 8 normal controls (Group 2) on 4 occasions after swallowing placebo, 0.5, 1.0 or 2.0 mg of the newly developed prokinetic drug renzapride given double-blind and in random order. The liquid component of the test meal was labelled with In113m and the solid with Tc99m. Liquid emptying was uni exponential. Solid emptying comprised an initial lag phase, followed by a linear component. Following placebo, the mean lag phase of solid emptying was 40 +/- 7 (S.E.M.) min in Group 1 and 16 +/- 2 min in Group 2 (P less than 0.01). In Group 1 subjects renzapride reduced the mean lag phase by 20-26 min at all doses (P less than 0.01). No effect was seen in Group 2. The linear rate of solid emptying was similar in both groups (0.9 +/- 0.1 and 1.0 +/- 0.2%/min) and was not altered by renzapride. Mean liquid t1/2 was similar in Groups 1 and 2 after placebo (30 +/- 6 and 29 +/- 4 min, respectively) and was decreased with increasing doses of renzapride in both groups. No adverse effects were encountered in any subjects. Renzapride may be useful in the treatment of diabetic gastroparesis. PMID- 1888817 TI - Nocturnal therapy with famotidine for 1 year is effective in preventing relapse of gastric ulcer. AB - A multicentre, double-blind, randomized, placebo-controlled trial was undertaken to investigate the therapeutic efficacy of a nocturnal dose of famotidine 20 mg to reduce the 1 year relapse rate of recently healed gastric ulcers. Twenty investigators in eight countries randomized 202 patients with endoscopically confirmed healed gastric ulcers. Repeat endoscopies were performed at 6 and 12 months or for symptoms compatible with ulcer relapse. A per protocol analysis of cumulative life table relapse at 12 months showed that famotidine 20 mg was superior to placebo in reducing gastric ulcer relapse, 24 versus 50%, respectively (P less than 0.01). Both placebo and famotidine were well tolerated. Since nocturnal dosing with famotidine 20 mg is effective in preventing gastric ulcer relapse over a 1-year period and is well tolerated, it offers a therapeutic option for the long-term treatment of patients with gastric ulcer. PMID- 1888818 TI - A controlled study of 20 mg famotidine nocte vs. 150 mg ranitidine nocte for the prevention of duodenal ulcer relapse. AB - A 24-week, double-blind, randomized study at 13 centres compared the efficacy and safety of 20 mg famotidine nocte and 150 mg ranitidine h.s. for the prevention of duodenal ulcer recurrence. All participants had been successfully treated for an acute duodenal ulcer with 40 mg famotidine nocte. Patients were endoscoped at baseline and at 24 weeks, unless symptoms warranted earlier examination: of the 208 patients enrolled, 86 who received famotidine and 84 who received ranitidine met all protocol criteria and were considered evaluable. Intention to treat and per protocol analyses showed non-significant trends in favour of famotidine (P = 0.44 and 0.16, respectively). During the 24-week observation period, 16.3% of the famotidine group and 25% of the ranitidine group had an ulcer recurrence (95% CI of percentage difference -0.22 + 0.04). At 24 weeks, relief of day and night pain was reported by 81.2% and 91.8% of the famotidine-treated patients, respectively. The corresponding figures in the ranitidine group were 73.5% and 85.5%. No laboratory abnormalities related to the study-drugs were noted and only two drug related (possibly or probably) adverse experiences were reported, both in the famotidine group. The data from this study therefore, supports the conclusion that the efficacy of 20 mg famotidine nocte is comparable to that of ranitidine in preventing duodenal ulcer recurrence, with comparable tolerability for long term therapy. PMID- 1888819 TI - Cimetidine suspension in patients with stage 0 gastro-oesophageal reflux disease. AB - One hundred and twenty-five patients with symptoms of heartburn and acid regurgitation but without endoscopic abnormalities were randomized to receive 200 mg cimetidine suspension four times daily or placebo for two weeks. Daily dairy cards were kept to evaluate the frequency and degree of symptoms. At two weeks cimetidine was significantly more effective than placebo. It is concluded that placebo suspension has a considerable effect on gastro-oesophageal reflux disease symptoms, but cimetidine suspension provides significantly better relief. PMID- 1888820 TI - Fluconazole for oropharyngeal candidiasis in anti-HIV positive haemophiliacs. AB - Candidiasis of the oropharynx and oesophagus is one of the most common problems encountered in patients with HIV disease. Fluconazole is a bis-triazole antifungal agent with a long serum half-life. Sixteen anti-HIV positive patients (15 haemophiliacs and one blood transfusion recipient) with a clinical diagnosis of oropharyngeal candidiasis were treated with 50 mg fluconazole daily for 14-28 days and then either 150 mg fluconazole or placebo weekly for 6 months in a prophylactic phase. Clinical cure occurred in all patients, and mycological cure occurred in 13/16 (81%) patients. In the prophylactic phase, there were 2/5 (40%) relapses in the placebo arm compared with 1/8 (12.5%) in the fluconazole arm, but this was not statistically significant by Fisher's one-sided exact test (P = 0.31). It is concluded that fluconazole is an effective treatment of oropharyngeal candidiasis and has potential for prophylactic use. PMID- 1888821 TI - Short report: lipid and vitamin B12 malassimilation in pancreatic insufficiency. AB - Patients with exocrine pancreatic insufficiency have steatorrhoea as well as vitamin B12 malassimilation. To investigate whether this is caused by the pancreatic insufficiency per se or whether intestinal bacterial overgrowth contributes to the condition, 10 patients with pancreatic steatorrhoea were studied. Intestinal culture was done. Lipid and vitamin B12 assimilation was estimated from faecal spot tests, using 14C-triolein and 58Co-vitamin B12 as tracers and 51CrCl3 as marker. Out of the 10 patients, 9 had either vitamin B12 malassimilation (n = 8), and/or bacterial overgrowth (n = 5). These 9 patients were retested with pancreatic enzyme therapy, with and without addition of the antibiotics metronidazole and cefalexin. The lipid assimilation was significantly increased by enzyme therapy but did not improve further on additional antibiotic treatment. The vitamin B12 assimilation did not improve significantly on enzyme therapy nor with additional antibiotic treatment. PMID- 1888822 TI - Review article: improved preservation of the liver for transplantation. AB - This paper reviews the development of the techniques used for liver preservation and describes their clinical use. Recent advances with the introduction of lactobionate based solutions for simple cold storage are described and illustrated by their effect on the Cambridge/King's College Hospital transplant programmes. Better preservation of the liver has simplified the logistics of the transplant procedure, improving organ usage and allowing increased sharing of livers for urgent or paediatric cases. PMID- 1888823 TI - Ranitidine in the treatment of duodenal ulcer disease: relationship between antisecretory effect and ulcer healing rate. AB - The relationship between drug-induced suppression of intragastric acidity and the rate of duodenal ulcer healing was examined using data for a single drug, ranitidine, from 156 clinical trials involving 16,362 patients together with data on acid suppression from 37 studies of intragastric acidity in 630 subjects. In these studies ranitidine was given in doses ranging from 150 mg to 1200 mg per day administered in 9 different dosage regimens. The overall percentage of patients whose duodenal ulcers healed at 2 and 4 weeks on the different regimens was highly correlated with the percentage suppression of 24-hour intragastric acidity induced by different regimens. Thus the therapeutic benefit of a given ranitidine dosage regimen in healing duodenal ulcers relates directly to its antisecretory effect. PMID- 1888824 TI - Dose-related healing of duodenal ulcer with the proton pump inhibitor lansoprazole. AB - Lansoprazole (AG 1749) is a novel substituted benzimidazole which inhibits gastric acid secretion by blocking H+,K(+)-ATPase. This randomized, double-blind multicentre trial studied the dose-response relationship of lansoprazole on ulcer healing and compared it with ranitidine in 314 out-patients with endoscopically assessed, symptomatic duodenal ulcer. Cumulative healing rates with Lansoprazole 7.5, 15, and 30 mg o.m. were 48, 59, and 74% at 2 weeks and 75, 84, and 95% at 4 weeks, respectively (intention-to-treat); the difference of the healing rates between 7.5 and 30 mg groups was significant (P less than 0.001). Corresponding healing rates for 300 mg ranitidine nocte were 51 and 89%. Pain relief was similar in all treatment groups. Lansoprazole was well tolerated. During a follow up of 6 months relapse rates after lansoprazole 7.5, 15, and 30 mg were 21, 29, and 22%, respectively; the relapse rate after ranitidine 300 mg was 20%. In conclusion, lansoprazole provides faster healing of duodenal ulcer than ranitidine and a similar relapse pattern. For further trials in peptic ulcer disease a daily dose of lansoprazole 30 mg o.m. is recommended. PMID- 1888825 TI - The effect of ranitidine, cimetidine or famotidine on low-dose post-prandial alcohol absorption. AB - Plasma alcohol concentration following oral ingestion of 0.3 g/kg of alcohol (ethyl alcohol), one hour after an evening meal, was measured in four groups of 12 healthy subjects. Each group had a control study and a repeat study after 7 days dosing with either placebo or an H2-receptor antagonist (300 mg ranitidine nocte, 800 mg cimetidine nocte, or 40 mg famotidine nocte). There was no significant difference between the control and post-dosing studies in the integrated 4-h plasma alcohol concentration, peak plasma alcohol concentration, or time to reach peak alcohol concentration. This study shows that post-prandial alcohol absorption after 0.3 g/kg of alcohol is not affected by ranitidine, cimetidine or famotidine. PMID- 1888826 TI - Assessment of water and solute absorption from experimental hypotonic and established oral rehydration solutions in secreting rat intestine. AB - Water and solute absorption from three experimental hypotonic oral rehydration solutions (HYPO-ORS; sodium 45, 60 and 75 mmol/L, glucose 90 mmol/L), the World Health Organization recommended ORS (WHO-ORS; sodium 90 mmol/L, glucose 111 mmol/L), and the British National Formulary recommended ORS (BNF-ORS; sodium 35 mmol/L, glucose 200 mmol/L), have been assessed by perfusion studies in cholera toxin-induced secreting rat intestine. Net water absorption was greatest from the most hypotonic solution (HYPO-45; P less than 0.05). UK-ORS prevented net water secretion and WHO-ORS promoted moderate net water absorption. Net sodium secretion was seen with all solutions but was least from WHO-ORS and greatest with BNF-ORS (P less than 0.01). Glucose absorption was similar from BNF-ORS, WHO ORS and HYPO-45 and in each case was greater than glucose absorption from HYPO-60 and HYPO-75 (P less than 0.05). These results suggest that net water and sodium absorption from ORS may be enhanced if osmolality is reduced by decreasing the glucose content. PMID- 1888827 TI - Eradication of Helicobacter pylori abolishes 24-hour hypergastrinaemia: a prospective study in healthy subjects. AB - In a prospective study, eight young healthy subjects (five with an active H. pylori infection in the antral mucosa) were treated with a course of tripotassium dicitrato bismuthate, amoxycillin and metronidazole. The triple therapy eradicated infection when assessed 20-24 weeks later by antral biopsy (urease, histology, and 13C urea breath test [4 out of 5 subjects]). Twenty-four hour intragastric acidity and plasma gastrin concentration were measured before treatment, and 4-6 weeks and 20-24 weeks post-treatment. Treatment did not affect acidity in either the H. pylori-positive or H. pylori-negative groups, nor did it affect the plasma gastrin profile in the H. pylori-negative group. Eradication of H. pylori infection in five subjects caused a drop of the median integrated 24 hour plasma gastrin concentration from 558 pmol.h/L before treatment to 307 and 289 pmol.h/L at 4-6 and 20-24 weeks post-treatment, respectively. It is concluded that H. pylori infection is associated with 24-hour hypergastrinaemia, and that in apparently healthy subjects normal gastric physiology can be restored by eradication of the infection. PMID- 1888828 TI - Steady-state pharmacokinetics of enteric coated 5-amino-salicylic acid tablets in healthy volunteers and in patients with Crohn's disease or ulcerative colitis. AB - An Eudragit-L coated oral 5-aminosalicylic acid (5-ASA; mesalazine) product (Mesasal), has been formulated to deliver 5-ASA to the distal small bowel and colon for the treatment of inflammatory bowel disease. The purpose of this study was to compare the pharmacokinetic profile of this product at steady-state between healthy volunteers and two different patient groups with inflammation of either the small or the large bowel. Two carefully selected groups of patients, nine with Crohn's disease restricted to the small intestine and ten with total ulcerative colitis and one group of ten healthy volunteers received two 250 mg Mesasal tablets three times daily for 10 days to reach steady-state. Plasma 5-ASA and acetyl-5-ASA concentrations were followed for 48 h and urinary excretion for 72 h. There was a great variation in most pharmacokinetic parameters within each group and no significant differences were noticed between the groups. The location of the inflammatory process probably does not influence the pharmacokinetics of 5-ASA in any significant way in patients with either Crohn's disease in the small bowel or total ulcerative colitis. PMID- 1888829 TI - Omeprazole and Helicobacter pylori: temporary suppression rather than true eradication. AB - Twenty-four Helicobacter pylori (H. pylori)-positive patients were treated for 28 days with either 20 mg omeprazole o.m. (n = 12) or 40 mg omeprazole o.m. (n = 12). Clearance (absence of H. pylori at the end of or shortly after treatment) and eradication (absence of H. pylori 1 month after cessation of treatment) were assessed using the 14C-urea breath test. Observed clearance and eradication were: 20 mg omeprazole 3/12 and 0/12; 40 mg omeprazole 6/12 and 1/12 respectively. The effect on H. pylori is probably due to the change in gastric pH from acid to neutral, however it is insufficient to recommend the inclusion of omeprazole in regimens aimed at eradicating H. pylori. PMID- 1888830 TI - Effects of ranitidine on maternal gastric juice and neonates when administered prior to caesarean section. AB - Ranitidine hydrochloride, a histamine H2-receptor antagonist, was intravenously administered to 61 pregnant women at a dose of 50 mg as premedication for caesarean section; its effects on gastric secretion were studied in the mother and the newborn. The volume of the maternal gastric juice collected immediately after the induction of anaesthesia averaged 14.0 +/- 10.0 ml with pH 3.48 +/- 1.70, and at the time of extubation, 3.6 +/- 2.8 ml with pH 4.19 +/- 1.79, respectively. Forty-four full-term neonates whose mothers had received ranitidine were selected to investigate the effects of ranitidine. Another 45 full-term normal newborns delivered vaginally, and 14 by caesarean section, served as controls. No effects of ranitidine infusion in the mothers were detected in the newborn children. The gastric pH of the newborn at birth and 24 hours after birth, gastrointestinal symptoms and the general growth checked at the regular one-month work-up after birth did not differ in test and control groups. PMID- 1888831 TI - Challenges in acid/peptic disorders: a symposium overview. AB - Before 1977, the treatment of peptic ulcer disease consisted primarily of dietary, antacid, and anticholinergic programmes. There were heated controversies regarding rigid vs. liberal ulcer diets, a variety of antacids and dosing patterns to choose from, and conflicting claims over the benefit of various anticholinergic therapies. It was hoped that the dramatic introduction of the H2 receptor antagonists would simplify our approach to the treatment of peptic ulcer and reflux oesophagitis. Standard doses of H2-receptor antagonists are effective for acid/peptic disorders, yet it has become clear that some subsets of patients present special management problems, including recurrent ulcers, non-steroidal anti-inflammatory drug (NSAID)-induced disease, stress ulcers, and refractory oesophagitis. New regimens, such as maintenance therapy and once-daily nocturnal dosing, have been indicated for peptic ulcer disease. New drugs have been introduced, such as sucralfate, misoprostol, and omeprazole, each with a different mechanism of action. Therefore, while we have learned considerably more about the pathogenesis of peptic disease, treatment decisions have become more complicated. The Transatlantic Conference on Acid/Peptic Disorders was held on 19 21 January 1990, in Wesley Chapel, Florida. A faculty from the United Kingdom, the United States, and Canada reviewed pathophysiology and the role of pharmacologic agents in the treatment of acid/peptic disorders and outlined clinically useful treatment strategies. The conference was organized into five segments: acid suppression and ulcer healing; acid suppression and control of reflux disease; NSAID-induced ulceration; stress ulceration, rationale for control of rebleeding, and drug interactions; and controversies. The proceedings of the symposium are presented in this supplement. PMID- 1888832 TI - Helicobacter pylori: review of research findings. AB - Helicobacter pylori attracted widespread interest from gastroenterologists because of its potential aetiologic role in disorders of the upper gastrointestinal tract. Based on extensive microbiological studies, Campylobacter pylori was renamed Helicobacter pylori, and the organism represents a new genus of bacteria. It is generally accepted that H. pylori causes chronic, non-specific gastritis (type B gastritis). The inflammatory response occurs even though the bacterium does not penetrate the gastric epithelium; it is found on the surface of and adjacent to the epithelium. The clinical significance of histological gastritis is unknown. The bacterium is often found in asymptomatic subjects. In Caucasian adults, the prevalence of infection increases with increasing age. Higher rates of infection are found in blacks and Hispanics than would be expected for their age. Whether these different rates are the result of racial or socioeconomic factors is not known. It is theorized, but not proven, that high rates of infection with H. pylori at an early age may explain the high incidence of gastric carcinoma found in Hispanic populations. H. pylori is found in almost every patient with duodenal ulcer disease, although no direct evidence for a causal relationship exists. Indirect evidence is based on the findings that if H. pylori infection is eradicated, ulcer recurrence is less likely (up to one year of follow-up). A small percentage of patients have a relapse despite eradication of the organism, suggesting a role for other factors in duodenal ulcer disease. The role of H. pylori in gastric ulcer disease is unknown. Seventy to eighty per cent of patients with gastric ulcer have evidence of H. pylori infection, and preliminary data seem to support the existence of two distinct aetiologic groups: those with gastric ulcers related to H. pylori infection and those with gastric ulcers related to use of non-steroidal anti-inflammatory drugs. The role of H. pylori in non-ulcer dyspepsia is unknown. Some clinicians believe that H. pylori causes non-ulcer dyspepsia and treat these patients for H. pylori infection. However, the data supporting this practice are poor. Treatment is only recommended for patients with resistant duodenal ulcers and patients who have frequent relapses of duodenal ulcers and who are willing to take triple-drug therapy (bismuth compounds, metronidazole, tetracycline) for the infection. As 95% of patients with duodenal ulcer have evidence of H. pylori infection, there is probably little need to confirm the diagnosis of H. pylori infection. PMID- 1888833 TI - Non-ulcer dyspepsia: myths and realities. AB - Dyspepsia can be defined as the presence of upper abdominal pain or discomfort; other symptoms referable to the proximal gastrointestinal tract, such as nausea, early satiety, and bloating, may also be present. Symptoms may or may not be meal related. To be termed chronic, dyspepsia should have been present for three months or longer. Over half the patients who present with chronic dyspepsia have no evidence of peptic ulceration, other focal lesions, or systemic disease and are diagnosed as having non-ulcer (or functional) dyspepsia. Non-ulcer dyspepsia is a heterogeneous syndrome. It has been proposed that this entity can be subdivided into a number of symptomatic clusters or groupings that suggest possible underlying pathogenetic mechanisms. These groupings include ulcer-like dyspepsia (typical symptoms of peptic ulcer are present), dysmotility (stasis) like dyspepsia (symptoms include nausea, early satiety, bloating, and belching that suggest gastric stasis or small intestinal dysmotility), and reflux-like dyspepsia (heartburn or acid regurgitation accompanies upper abdominal pain or discomfort). The aetiology of non-ulcer dyspepsia is not established, although it is likely a multifactorial disorder. Motility abnormalities may be important in a subset of dyspepsia patients but probably do not explain the symptoms in the majority. Epidemiological studies have not convincingly demonstrated an association between Helicobacter pylori and non-ulcer dyspepsia. Other potential aetiological mechanisms, such as increased gastric acid secretion, psychological factors, life-event stress, and dietary factors, have not been established as causes of non-ulcer dyspepsia. Management of non-ulcer dyspepsia is difficult because its pathogenesis is poorly understood and is confounded because of a high placebo response rate. Until more data are available, it seems reasonable that treatment regimens target the clinical groupings described above. Antacids are no more effective than placebo in non-ulcer dyspepsia, although a subgroup of non ulcer dyspepsia patients with reflux-like or ulcer-like symptoms may respond to H2-receptor antagonists. However, there is no significant benefit of these agents over placebo in many cases. Bismuth has been shown to be superior to placebo in patients with H. pylori in a number of studies, but these trials had several shortcomings and others have reported conflicting findings. Sucralfate was demonstrated in one study to be superior to placebo, but this finding was not confirmed by another group of investigators. Prokinetic drugs appear to be efficacious, and may be most useful in patients with dysmotility-like and reflux like dyspepsia. PMID- 1888834 TI - Idiopathic gastric acid hypersecretion: treatment implications for refractory acid/peptic disorders. AB - Although in most patients with duodenal ulcer disease the ulcer heals after 8 weeks of treatment with standard doses of H2 blockers or other agents, in about 10% the ulcer does not heal. These patients are considered 'refractory' to treatment. Reasons often cited for non-healing include poor patient compliance, cigarette smoking, and non-steroidal anti-inflammatory drug (NSAID) use. Gastric acid hypersecretion also appears to be an important factor in non-healing with standard doses of antisecretory agents. We have defined idiopathic gastric acid hypersecretion as a basal acid output of greater than 10 mmol/h in the absence of an elevated fasting serum gastrin level (or a negative secretin test if gastrin level greater than 100 pg/ml) to exclude persons with Zollinger-Ellison syndrome. Among the acid/peptic-related disorders in which idiopathic gastric acid hypersecretion should be considered are refractory duodenal ulcer, refractory gastro-oesophageal reflux disease (especially patients with oesophagitis), postbleeding duodenal ulcer, and certain rare disorders such as hereditary angioedema. Some children with atypical abdominal pain may also be hypersecretors of gastric acid. Once identified, patients with refractory duodenal ulcer or gastro-oesophageal reflux disease are treated with incremental doses of ranitidine titrated against the level of gastric acid secretion that remains during therapy. Ranitidine was selected to avoid the dose-related antiandrogenic effects and potential hepatic cytochrome P450 system-related drug interactions that may occur with cimetidine. In most cases of refractory duodenal ulcer, doubling the standard dose of ranitidine (to 300 mg b.d.) is sufficient to achieve symptomatic relief and mucosal healing. Higher doses appear to be necessary for refractory oesophagitis. To date, no side effects have been associated with high doses of ranitidine (up to 1800 mg/day) for periods of longer than 6 months. Idiopathic gastric acid hypersecretion is an important factor in explaining why not all patients respond to a 'standard' ulcer-healing dose of H2 blocker, and it provides a rationale for use of higher-dose therapy as a safe and effective alternative to omeprazole or to combination drug therapy in refractory acid/peptic disease. PMID- 1888835 TI - Degrees of acid suppression and ulcer healing: dosage considerations. AB - The human stomach has a normal circadian rhythm of intragastric acidity characterized by increasing acidity during the day and peaks in the early hours of the morning. Eating causes a transient decrease of intragastric acidity. Acid appears to be the permissive factor in peptic ulcer disease and to be responsible for symptoms; the patient with duodenal ulcer may secrete too much acid. Pharmacological control of gastric acid secretion will speed ulcer healing. Modern regimens, which typically use a bedtime dose of an H2-receptor antagonist, produce a pulse of decreased acidity. Intragastric acidity is decreased during the night and early morning, leaving a normal profile of acidity during the day and early evening. Higher or more frequent doses of an antisecretory agent can produce a more profound decrease of 24-h intragastric acidity. Theoretical problems associated with a sustained or profound decrease of 24-h intragastric acidity include the threat of enteric infection and infestation, potential bacterial overgrowth with possible N-nitrosamine formation, and drug-induced hypergastrinaemia. In light of these potential problems, for the management of simple peptic ulceration, it appears sensible to use the minimum intervention required. Bedtime H2-receptor blockade is one such regimen. The more potent antisecretory regimens can be used for difficult clinical problems such as the Zollinger-Ellison syndrome, intractable duodenal ulceration, and severe oesophagitis. PMID- 1888837 TI - Pathophysiology of NSAID-induced gastroduodenal damage: epidemiology and mechanisms of action of therapeutic agents. AB - All NSAIDs cause gastroduodenal mucosal damage. The mechanisms by which NSAIDs damage the mucosa are not fully understood. Peptic ulcers appear to be caused by an imbalance between acid output and mucosal resistance; therapeutic agents that act favourably on either variable will heal NSAID-induced ulcers, particularly if the NSAID is discontinued. Inhibition of acid secretion and/or stimulation of prostaglandin secretion are also believed to have a protective effect against NSAID-induced mucosal damage. Thus, antisecretory agents, such as the H2 blockers, and prostaglandin analogues, such as misoprostol, can provide protection against NSAID-induced gastroduodenal damage. PMID- 1888836 TI - Quality of gastric ulcer healing: histological and ultrastructural assessment. AB - It has long been assumed that the mucosa in areas of grossly 'healed' gastric or duodenal ulcers returns to normal, either spontaneously or after treatment. This assumption is based almost entirely upon visual, superficial examination by endoscopy. Few, if any, histological and ultrastructural studies examined the deeper mucosa in the areas of grossly healed ulcers. In several experimental studies, we analysed the development, evolution, and healing of acetic acid induced gastric ulcers in rats and assessed the histological and ultrastructural features (structure and cellular composition) of the gastric mucosa in areas of grossly healed ulcers. The gastric mucosa of grossly 'healed' ulcers showed re epithelialization of the mucosal surface at every study interval (2 weeks, 2, 3, and 4 months), but the subepithelial mucosa displayed prominent abnormalities. Two patterns of scarring were distinguished: (a) the mucosa in the area of healed ulcer was thinner (25-45% thinner than normal mucosa) with increased connective tissue and poor differentiation and/or degenerative changes in the glandular cells; and (b) the mucosa displayed a marked dilation of gastric glands with poor differentiation of the glandular cells and a reduction in the supportive microvascular network. It is theorized that these abnormalities could interfere with oxygenation, nutrient supply, and mucosal resistance and defence; therefore, they could be a basis for ulcer recurrence. These observations indicate that the quality of mucosal structural restoration rather than the speed of ulcer healing is the most important factor in determining risk of ulcer recurrence. The clinical relevance of these findings is supported by a preliminary study in which marked histological abnormalities were found in the subepithelial mucosa in patients with 'healed' duodenal ulcers. PMID- 1888838 TI - [Visceral obesity, a metabolic entity with vascular risk]. PMID- 1888839 TI - [Long term follow-up of non-symptomatic HBsAg carriers]. AB - 232 asymptomatic HBsAg carriers were controlled between May/1986 and May/1990. The were detected in our blood bank between 1974 and 1976 or during pregnancy or delivery period after 1981. 23 of 232 (10%) became negative during the follow-up, this happening more frequently in carriers after 5 years of follow-up. Only 2 of 209 carriers with HBsAg were HBeAg positive and 1 of these was also DNA-VHB positive. None of the HBeAg negative carriers showed DNA-VHB; only 5 had increased transaminases. 7 were anti-VHC positive, these individuals experiencing more frequent increases in transaminases. The results of this study suggests that the determination of transaminases, viral activity markers, anti-HD, anti-VHC in HBsAg carriers are enough to identify those with hepatic disease. PMID- 1888840 TI - [Cefotaxime treatment of osteomyelitis of the foot in the diabetic]. AB - Osteomyelitis at the base of an ulcer the foot of diabetic patient is a serious complication usually produced because of the patient's neglect, and entailing difficulties in diagnosis and treatment. Several factors (neurological and vascular ...) favor the onset of the initial ulcer and its evolution, the ulcer subsequently converting into the main door for soft tissue infection with extension to the contiguous bone, with a bad prognosis. Cefotaxime is a 3rd generation cephalosporin, active against coccus gram positive and the majority of aerobic gram negative bacillus. This antibiotic was used in 25 diabetic patients with osteomyelitis at a dosage of 2 gr. IV a/d, during at least 30 days, adding metronidazole when anaerobic bacteria were isolated. The number of patients cured were 21 (84%), one improvement (4%), one resistant (4%) and two relapses (8%). There were no secondary effects. PMID- 1888841 TI - [Pigmented erythema: a marker of alcoholism]. AB - The aim of this paper is to describe the association between chronic alcoholism and pigmented erythema in the lower limbs. 489 patients were prospectively registered for this study; a significant association was observed between chronic alcoholism and pigmented erythema (prevalence 41,95 in alcoholics and 14.29 in nonalcoholics. x2 = 47.57; p less than 0.0001; OR = 4.274, confidence interval (CI) = 6.49-2.81); being more evident in patients under 60 years old (40% in alcoholics and 5.94 in non-alcoholics. x2 = 37.36; p less than 0.0001; OR = 9,21; IC = 4.29-19.77). Alcoholics with erythema tended to be the older ones, however, at the same time, they were younger than the non-alcoholic patients with erythema. Erythema was associated to the period time of ethanol addiction. Thus, we concluded that pigmented erythema can be considered a new alcoholism marker. PMID- 1888842 TI - [Comparative morbidity study 1984-1989 in the internal medicine department of a second-level general hospital]. AB - In order to determine the changes in the clinico-pathological pattern of admitted patients in an internal medicine department, 240 patients/year were compared during the years 1984 and 1989. A predominant proportion of males was registered (3:2); which did not vary by the year. An increased tendency of the median age (55.78 vs 58.48 years) was also established. The medium time of admission (8.98 vs 9.5 days) and mortality rate (6.3% vs 7.1%) did not change. A high rate (greater than 50%) of cardiovascular and respiratory disease was found on analyzing the cause of admission; in 1989 infection caused by HIV was detected and admissions to optimize the treatment of patients with diabetes mellitus were observed which did not exist in 1984. A slight but surprising decrease in admissions due to acute ischemic cardiopathy and significant decrease of admissions owing to respiratory disease were also noted. The majority of the patients admitted had a baseline disease (85% in 1984 and 87.1% in 1989). The knowledge of these data and their variations in every hospital department will, undoubtedly, assist in achieving a better use of technical and human health resources. PMID- 1888843 TI - [Collagenous colitis associated with rheumatoid arthritis]. AB - A patient diagnosed as having well-tolerated rheumatoid arthritis and diarrhea is described. The female patient in question was diagnosed as suffering from collagenous colitis by means of a colon biopsy. The association of this clinical state with immunological disease is discussed. PMID- 1888844 TI - [Familial outbreak of pulmonary tuberculosis]. AB - A study of 5 patients diagnosed as having pulmonary tuberculosis during a period of 14 months is presented. 3 of them are members of the same family of 7 and the other 2 are closely related. This study calls our attention to the need for carrying out contacts evaluation, relative or not, and for chemoprophylaxis. The presentation of microepidemyes in relation to the decrease of the prevalence was also observed. PMID- 1888845 TI - [Gaucher's disease type I, anticoagulant factor and pregnancy]. AB - In this paper, we show the presence of an anticoagulant factor which induced a prolongation of the partial time of thromboplastin (PTT) in a 23 year old female with Gaucher's disease and premature delivery. We discuss the importance of this factor and the therapeutic efficacy of the total splenectomy in this type of patient when spleen enlargement poses problems for the evolution of pregnancy to the end. PMID- 1888846 TI - [Usefulness of 2-D ultrasound in diagnosis of pericardial partial defects]. AB - A case of 2 year old female, asymptomatic, was referred to this hospital in order that an abnormal radiological cardiac shape could be studied. Physical examination and ECG were normal. The 2-D ultrasound showed systolic deformation on the antero-lateral wall in the left ventricle, with an increased ecogenity and protrusion of the left earlobe to the left lung. A CT scan showed a defect of the pericardium at the same level. After the revision of the pericardium, we concluded that the use of an invasive test to diagnose this disease is not necessary, the 2-D ultrasound being enough to show the defect. PMID- 1888847 TI - [Cardiac diseases related to free radicals and active oxygen species. Pro oxidation and anti-oxidation in cardiology (part 2)]. AB - In this second part, we study in detail the most important cardiological diseases showing the physiopathological consideration to support the importance of the stationary equilibrium between pro-oxidation and anti-oxidation to maintain the cardiovascular health. Ischemic cardiopathy and its risk factors (lipids, smoke, blood hypertension, alcohol, etc.), anti-oxidation, different cardiac diseases (coronary insufficiency, blood hypertension, congestive heart insufficiency, cardiomyopathies), are analyzed, and finally, we make clear certain information related to the onset of nitrites tolerance phenomenon and its treatment with anti oxidation products. PMID- 1888848 TI - [Psittacosis as a cause of severe acute respiratory insufficiency: first case of this infection in the Canary Islands]. PMID- 1888849 TI - [Smoldering multiple myeloma: 2 observations]. PMID- 1888850 TI - [Skin involvement as the first manifestation of an epidermoid carcinoma of the lung]. PMID- 1888851 TI - [Efficacy of roxithromycin in the treatment of lower respiratory tract infections in patients with chronic respiratory disease]. PMID- 1888852 TI - [Evolution of acquired aplastic anemia to myelodysplasia and posterior multiple myeloma]. PMID- 1888853 TI - [Severe accidental hypothermia. A case report with favorable outcome]. PMID- 1888854 TI - [Rhabdomyolysis and Q fever]. PMID- 1888855 TI - [A new case of Munchausen's syndrome]. PMID- 1888856 TI - [Intravascular coagulation and Mediterranean boutonneuse fever]. PMID- 1888857 TI - [Malnutrition in developed societies]. PMID- 1888858 TI - [Psychocutaneous diseases in primary care]. PMID- 1888859 TI - [Quality control of a computer system for repeat prescriptions]. AB - The results of a quality control of a computer system of repeated prescription (RPS) and its basic features are reported. The selected quality criteria were the following: reduction of the bureaucratic index in the visit, correct fulfillment of the treatment order, health attention circuits of the RPS, and compliance of the patient with the treatment. The record of activities and a random sample of treatment orders (TO) were used as sources of data. Quality indexes near the optimal standard (OS) were achieved: bureaucratic index 12.8% (OS = 15%), fulfillment of the TO 94% (OS = 100%), specified dosages 86% (OS = 100%), prescriptions in out-of-date orders 7% (OS = 0%), use higher than calculated 1% (OS = 0%), and use lower than calculated 36% (OS = 25%). Finally, the corrective measures for the detected quality problems are proposed, and the advantages of the computer RPS are discussed. PMID- 1888860 TI - [Physician-patient communication and health education]. AB - The aim of the present study was to analyze the content in health education of the patient-physician interview. The study was observational and descriptive. The target population were the patients attending the general practices of the Social Security clinics. With permission of patients and physicians, 53 visits of two general practitioners were recorded on tape. 48 interviews were analyzed with definition of activities (asking, answering, discussing, etc.) and contents (health problems, treatment, health education, etc.). Health education was 10% of the contents, and it was associated with the physician's activity of commenting/instructing and with the patient's activity of commenting/asking. PMID- 1888861 TI - [Evaluation of the use of digoxin in a primary care emergency service]. AB - Digoxin is a widely used drug. Previous studies suggest a high prevalence of inadequate use, subtherapeutic levels and high toxicity rates. The aim of the present study was to evaluation the use of digoxin in our area. 50 consecutive patients who attended our emergency service and who were receiving digoxin on a chronic basis were prospectively evaluated. There were 37 females and males, with age 78.1 +/- 8.6 years. We found that digoxin was not indicated in 12% of cases. Only 48% had digoxin plasma levels within the therapeutic range. When plasma levels were considered in association with clinical and electrocardiographic findings, 12% of patients were undertreated and 6% had digitalis toxicity. There was no relation between the digoxin plasma level and the dosage schedule, the ECG findings, the renal function, the use of other drugs or the anthropometric data. Emphasis is made on the need to individualize digoxin therapy and to measure plasma levels in particular cases. PMID- 1888862 TI - [Evaluation of compliance with appointments and the control of blood pressure in a group of hypertensive patients]. AB - The social and public health relevance of hypertension (HT) is well know. In the present study, 308 hypertensive patients were evaluated in two six month periods. An organized variation was carried out, consisting of the suppression of the scheduled visit with subsequent attention of the patient by visit on demand. The evaluated variables were the degree of compliance with the appointment and the control of the blood pressure levels in the two periods, depending on sex, age, and degree of hypertension. Better results were achieved during the first period (with scheduled visit), both regarding compliance and control. Therefore, it seems preferable to keep scheduled visits for the HT protocols. PMID- 1888863 TI - [Results of periodic health examinations in an adult population aged 15-60 years]. AB - We report the results of 510 periodical health examinations in adults aged 16-60 years (43% males and 57% females), carried out by the nursing staff in our center (belonging to the PAPPS of the SEMFyC). In the results there was a remarkably high rate of risk factors: 46.6% of obesity, 46% of smokers, 40% of sedentarism, 20% of hyperlipidemia, and 5.1% of hypertension. There was a higher prevalence of smokers among the female population between 15-44 years of age; 6.3% of the surveyed population consumed more than 50 g of alcohol/day, 3.7% had abnormal urine reactive strips and 1.6% had abnormal carbohydrate metabolism. In our experience, the periodical health examination perfectly fits the role of nurses and is well accepted by the population. PMID- 1888864 TI - [Prevalence of chronic lower limb ischemia in a population attending a health center]. AB - To evaluate the prevalence of chronic lower limb ischemia in a part of the population on care of the health center Les Borges Blanques (Lleida), a study of 305 subjects (131 males and 174 females over 59 years) who presented to the health center was carried out with case finding methodology. Chronic ischemia was detected in 27 patients (20 males and 7 females), with a 8.8% prevalence in males and 4% in females. The ratio was 4.5 times higher in males (p less than 0.001). A 40% of patients were aware of their disease; 44% had an adequate clinical control and 48% had intermittent claudication. It was concluded that the prevalence of the condition is high, with a good clinical control in less than one half of the patients. Early detection and adequate control of the patients is necessary. PMID- 1888865 TI - [Carpal tunnel syndrome: report of 3 cases]. AB - The carpal tunnel syndrome is a neuropathy due to trapping (focal lesion of the peripheral nerve due to a local cause); in this case, the median nerve is the most commonly involved. Its presentation is characteristic in females about 40 years of age. The diagnosis is mainly based on clinical features and is confirmed by electrical criteria. In the anamnesis it is important to consider systemic diseases as causing the abnormality. Treatment depends on the etiology. It may be medical or surgical. In the present article we report three cases with different etiology and treatment. We also review the syndrome. PMID- 1888866 TI - [Anxiety]. PMID- 1888867 TI - [The small intestine]. PMID- 1888868 TI - [Community-oriented primary care (I). Conceptual and methodological basis]. PMID- 1888869 TI - [On the general practice posts in the open examinations for appointing primary care teams]. PMID- 1888870 TI - [A study of health priorities by the Delphi method]. PMID- 1888871 TI - [Ischemic heart disease: mean age of onset, form of presentation and prevalence of coronary risk factors]. PMID- 1888872 TI - [Inadequate use of the term prevalence]. PMID- 1888873 TI - [Increased transaminase activity in children of carriers of surface antigen]. PMID- 1888874 TI - [A study of absenteeism in an urban primary care center]. PMID- 1888875 TI - [Gingival hyperplasia as an adverse reaction to nifedipine]. PMID- 1888876 TI - [Exploratory investigation on mental diseases in primary care]. PMID- 1888877 TI - Progressive changes from young adult age to senescence in mRNA for rat cardiac myosin heavy chain genes. AB - In rodents of an advanced age the cardiac contraction exhibits a reduced shortening velocity and prolonged time course. This is, in part, due to a reduction in myosin ATPase activity which results from a shift in the myosin heavy chains from the alpha (V1) to the beta (V3) isoform. The present study demonstrates that during adult aging the steady state levels of alpha myosin heavy chain mRNA decrease while those of beta myosin heavy chain increase; for both mRNAs the respective changes are greater than fourfold. Thus, the phenotypic, biophysical and biochemical cardiac contractile changes with adult aging are, at least, in part regulated at the level of gene expression. PMID- 1888878 TI - Histological evidence of increased turnover in bone from spontaneously hypertensive rats. AB - 24 weeks-old spontaneously hypertensive male rats and normotensive genetic controls were subjected to: histomorphometry of the proximal tibiae, assay of mineral density of the femurs by dual photon absorptiometry, and measurement of the calcium content of the femoral bone ash by atomic absorption spectophotometry. Compared with the controls, the hypertensive rats showed osteopenia and increased bone turnover; their osteoid volumes and the surface area of both osteoclasts and osteoblasts were all increased. The data suggest that, during aging, spontaneously hypertensive rats both lose bone mass more rapidly and also have an increased skeletal metabolic rate with respect to the controls. PMID- 1888879 TI - Acute effects of adriamycin on the macromolecular organization of the cardiac muscle cell plasma membrane. AB - Adriamycin is a potent chemotherapeutic agent used in the treatment of human neoplastic disease. A major side effect limiting the use of this drug is its toxic effect on the heart, and congestive heart failure becomes an increasingly common complication as the cumulative dose of the drug rises. To learn more about the mechanism of adriamycin cardiotoxicity and, in particular, to investigate its initial effects on the cardiac muscle cell plasma membrane, isolated guinea pig myocytes were exposed to the drug in vitro. Plasma membrane macromolecular structure was examined by freeze-fracture electron microscopy of myocytes exposed to 0.1, 1 and 2 mM adriamycin for periods up to 105 minutes. The principal effect of adriamycin was rapid induction of smooth (protein-poor) domains in the membrane, with displacement and clustering of intramembrane particles (the structures representing integral membrane proteins). These effects, which are time-dependent and dose-dependent, culminate in the formation of saucer-shaped lesions in the membrane, which broadly resemble deformations of the membrane induced by polymyxin B. Both adriamycin and polymyxin are known to have the ability to interact selectively with anionic phospholipids. It is concluded that an important initial effect of adriamycin on cardiac muscle cells is alteration of the macromolecular architecture of the plasma membrane, probably through interaction with anionic phospholipids, and that this may represent the underlying cause of a range of sarcolemmal dysfunctions associated with exposure to the drug. PMID- 1888880 TI - Fatty acids of hearts from rats fed linseed or sunflower oil and of cultured cardiomyocytes grown on their sera. AB - Rats were fed for 6 weeks a diet containing either sunflower oil or linseed oil. In each case, blood serum was subsequently collected and added to two media which were then used to grow cardiomyocytes. Under these conditions, the incorporation of omega 6 and omega 3 polyunsaturated fatty acids shows similar trends in hearts and cultured cardiomyocytes. The content of C22-unsaturated fatty acids was lower in the myocytes than in the hearts but the ratio of acids of the omega 6 series to those of the omega 3 series was similar. PMID- 1888881 TI - Echocardiography shows persistent thickness of the wall of the right ventricle in infants at high altitude. AB - We have applied M-mode and two-dimensional echocardiography to infants living at high altitude in La Paz, Bolivia (3800m) and infants living at low altitude in Santa Cruz, Bolivia (400m). At low altitude, the thickness of the anterior wall of the right ventricle decreases during the first month of extrauterine life to a dimension which remains constant for the rest of infancy. At high altitude, the thickness of the anterior wall of the right ventricle at birth is similar to that found at low altitude but does not decrease in the succeeding twelve months. The ratio of the diameter of the aorta to that of the pulmonary artery was higher at low altitude in all age-groups. The observations are consistent with the persistence of a high pulmonary arterial pressure during infancy at high altitude. PMID- 1888882 TI - Species differences in human and rat islet sensitivity to human cytokines. Monoclonal anti-interleukin-1 (IL-1) influences on direct and indirect IL-1 mediated islet effects. AB - Species differences in sensitivity to human recombinant cytokines were observed when human or rat islets were co-cultured with human recombinant cytokines for 6 days. Suppression of both human and rat islet insulin secretion resulted from co culture with recombinant interleukin-1 alpha (rIL-1 alpha) or interleukin-1 beta (rIL-1 beta); however, direct rIL-1 alpha and rIL-1 beta cytotoxicity was seen with rat islets but not with human islets. Human islet insulin secretion was also suppressed during co-culture with recombinant tumor necrosis factor (rTNF) or interferon (rIFN), but not with lymphotoxin (rLT) or rIL-6; rat islet insulin secretion was not suppressed by any of these cytokines. No direct cytotoxic effects resulted from co-culture of human islets with rLT, rTNF, rIFN, or rIL-6; rLT was slightly cytotoxic for rat islets. Human islet cytotoxic synergy occurred between rLT and rIL-1 alpha, rIL-1 beta, or rIFN; synergy in suppression of human islet insulin secretion occurred between rLT and rIL-1 beta, and between rIFN and rTNF. Pretreatment of rIL-1 with monoclonal antibody (mAb) specific for non crossreactive epitopes on rIL-1 alpha (H43 and H12) or rIL-1 beta (H34 and H21) prevented islet cytotoxic synergy between rIL-1 alpha or rIL-1 beta, respectively, and rLT. Although all four mAb's neutralize the thymocyte and fibroblast stimulatory activities of rIL-1 alpha or rIL-1 beta, mAb H21 does not neutralize rIL-1 beta activity against rat islets. Implications for cytokine mediated islet cytotoxicity and suppression of insulin secretion are discussed. PMID- 1888883 TI - Interleukin-1 suppresses mesangial cell growth via inhibition of Ca2+ entry. AB - We have investigated the effect of interleukin-1 (IL-1) on the cell growth and Ca2+ homeostasis of rat mesangial cells in culture. DNA synthesis measured by [3H]thymidine uptake by mesangial cells was significantly inhibited by IL-1 (10 U/ml) and the calcium channel antagonist nicardipine (5 x 10(-6) M). 45Ca2+ uptake by mesangial cells was also significantly inhibited by IL-1 and nicardipine. The above observations support the premise that IL-1 suppresses the growth of mesangial cells via inhibition of extracellular Ca2+ entry to the cytosol. PMID- 1888884 TI - Comparison of human interleukin-1 beta and its 163-171 peptide in bone resorption and the immune response. AB - Human interleukin-1 beta (IL-1 beta) caused a dose- and time-dependent enhancement of the release of 45Ca from prelabeled mouse calvaria in organ culture. In addition, IL-1 beta dose-dependently stimulated the formation of prostaglandin E2 (PGE2) and 6-keto-PGF1 alpha in the calvarial bones. However, IL 1 beta-induced 45Ca release was only partially inhibited by blocking the PGE2 response with indomethacin, suggesting that enhanced PGE2 formation in response to IL-1 beta is not necessary to obtain a bone resorptive effect, but that prostaglandins potentiate the action of IL-1 beta. The synthetic nonapeptide VQGEESNDK, corresponding to the fragment 163-171 of human IL-1 beta, administered simultaneously with antigen (SRBC) to C3H/HeN male mice, induced a dose-dependent enhancement of specific antibody-producing cells in the spleen (PFC). The degree of PFC stimulation was comparable to that caused by native human IL-1 beta. In mouse bone cultures, neither 45Ca release nor prostanoid formation was stimulated by fragment 163-171. These data indicate that (1) IL-1 beta-induced stimulation of bone resorption is dissociable from IL-1 beta-induced increase of prostanoid biosynthesis and (2) the epitope of the IL-1 beta molecule involved in the immunostimulatory effects may be different from that involved in the stimulatory effects on bone resorption. PMID- 1888886 TI - Interleukin-6 induces the (2'-5') oligoadenylate synthetase gene in M1 cells through an effect on the interferon-responsive enhancer. AB - Interleukin-6 (IL-6) activates (2'-5') A synthetase (2'-5' AS) gene expression in differentiating myeloleukemic M1 cells. Antibodies to type I interferon (IFN) inhibit 2'-5' AS induction but not differentiation. Analysis of the mechanism of 2'-5' AS induction shows that it does not result from increased IFN formation, but from a synergism between IL-6 and endogenously secreted IFN. IL-6 can activate expression of a CAT construct fused to the interferon response sequence (IRS) of the 2'-5' AS gene. In extracts of IL-6-treated M1 cells, changes in protein binding to IRS DNA can be demonstrated. One of the effects of IL-6 on M1 cells is, therefore, to induce DNA binding factors, some of which act on the same enhancer sequence as IFNs, resulting in a synergistic gene activation. M1 variants resistant to differentiation by IL-6 have lost the ability to induce the 2'-5' AS gene. PMID- 1888885 TI - Cytokines in normal and abnormal parturition: elevated amniotic fluid interleukin 6 levels in women with premature rupture of membranes associated with intrauterine infection. AB - The participation of interleukin-6 (IL-6) in the pathophysiology of normal and abnormal human parturition was evaluated by determining IL-6 concentrations in amniotic fluid (AF). Biologically active IL-6 was determined (in U/ml) using the B9 hybridoma growth factor assay, while the concentrations of immunoreactive IL-6 species (in pg/ml) were assessed using a monoclonal antibody (moAb)-based ELISA. Two hundred and twenty-seven AF samples from women in normal labor and from those presenting with a clinical diagnosis of premature rupture of membranes (PROM) were assayed. In selected instances, IL-6 levels were evaluated simultaneously in AF and in maternal and fetal plasma. Women with a normal pregnancy had low titers of biologically active IL-6 in AF both at midtrimester (group 1, n = 27; median IL-6 concentration = 16 U/ml) and at term (group 2, n = 33; median = 15 U/ml). There was an increase in the IL-6 bioactivity in AF from women in normal labor at term (group 3, n = 40; median = 74 U/ml; p less than 0.001). In order to distinguish between the relative contributions of parturition per se and of intrauterine infection to the elevation of biologically active IL-6 levels in AF, IL-6 titers were compared in four different groups of women with PROM.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1888887 TI - The immunobiology of murine interleukin-1 alpha encoded by recombinant vaccinia virus. AB - Recombinant vaccinia viruses were constructed which encoded murine interleukin-1 alpha (IL-1 alpha) (VV-IL1). One virus also encoded the hemagglutinin (HA) gene of influenza virus (VV-HA-IL1). Mice were infected with these viruses and the effects of co-expressed IL-1 on various immune parameters were assessed. The growth of VV-IL1 in vivo was less than that of the control virus, and this was reflected in the reduced virus-induced cell-mediated immune responses. However, specific antibody responses generated after challenge with vaccinia or influenza viruses were significantly higher when VV-HA-IL1 was used to prime mice, compared to the control virus (VV-HA-TK). This study demonstrates that co-expressed cytokines may be useful for selective alteration of immune reactivity. PMID- 1888888 TI - 24th annual meeting of the American Society of Nephrology (ASN). November 17-20, 1991. Program and abstracts. PMID- 1888889 TI - Gene structure and expression of a tobacco endochitinase gene in suspension cultured tobacco cells. AB - We have isolated and characterized the genomic clone lambda CHN50 corresponding to tobacco basic endochitinase (E.C.3.2.1.14). DNA sequence and blotting analysis reveal that the coding sequence of the gene present on lambda CHN50 is identical to that of the cDNA clone pCHN50 and, moreover, the CHN50 gene has its origin in the progenitor of tobacco, Nicotiana sylvestris. Tobacco basic chitinases are encoded by a small gene family that consists of at least two members, the CHN50 gene and a closely related CHN17 gene which was characterized previously. By northern blot analysis, it is shown that the CHN50 gene is highly expressed in suspension-cultured tobacco cells and the mRNA accumulates at late logarithmic growth phase. To identify cis-DNA elements involved in the expression of the CHN50 gene in suspension-cultured cells, the chimeric gene consisting of 1.1 kb CHN50 5' upstream region fused to the coding sequence of beta-glucuronidase (GUS) was introduced by electroporation into protoplasts isolated from suspension cultured tobacco cells. Transient GUS activity was found to be dependent on the growth phase of the cultured cells, from which protoplasts had been prepared. Functional analysis of 5' deletions suggests that the distal region between -788 and -345 contains sequences that potentiate the high-level expression in tobacco protoplasts and the region (-68 to -47) proximal to the TATA box functions as a putative silencer. PMID- 1888890 TI - Cytokinin content and tissue distribution in plants transformed by a reconstructed isopentenyl transferase gene. AB - The cytokinin gene, isopentenyl transferase (ipt), was placed under the control of a heat-inducible promoter from the Drosophila melanogaster hsp70 gene and introduced into Nicotiana plumbaginifolia by cocultivation with Agrobacterium tumefaciens. Transformants were analyzed for organ-specific expression, cytokinin levels and effects on plant development before and after the heat induction. The ipt gene transcripts were detected in leaves and stems but not roots of transgenic plants following a 2 hour, 45 degrees C treatment. Maximum mRNA levels observed occurred 2 hours after heat treatment and 46 hours later were detected only in leaves. Zeatin and zeatinriboside concentrations 2 hours after heat shock ranged from over 900 to 2000 pmol/g, representing a greater than 140- to 200-fold increase over uninduced levels. After 46 hours, approximately 50% of the cytokinins are still present in the leaves as opposed to much reduced levels in the stems. Transgenic plants were greener, shorter, had an underdeveloped root system, reduced leaf width, and increased growth of axillary buds. After a single heat treatment, plants exhibited a darker green pigment and continued growth of lateral buds. Transient accumulations of endogenous cytokinins following thermal induction did not appear to alter the plant's preprogrammed pattern of differentiation. PMID- 1888891 TI - Molecular analysis of two PR-1 pseudogenes from tobacco. AB - Two independent PR-1 lambda genomic clones (W38/1 and W38/3) were isolated and characterized from a tobacco (Nicotiana tabacum cv. Wisconsin 38) library. Neither clone is identical to the previously described PR-1 cDNA clones, and both clones carry mutations within the highly conserved PR-1 protein coding region. For example, clone W38/1 has a GAA Glu codon instead of the translation stop codon thus harbouring an open reading frame extended by 16 additional amino acids. Furthermore, both clones display considerable variations in the genomic flanking sequences when compared to the PR-1a gene. In order to test whether the encoded genes are active, their upstream sequences were fused to the E. coli beta glucuronidase (GUS) reporter gene. While significant GUS activities as compared to the 35S RNA promoter from cauliflower mosaic virus (CaMV) were obtained with the W38/1 and W38/3 sequences in transient gene expression assays, no transcriptional activities could be observed upon stable transformation of the same constructs. In addition, the protein coding region of W38/1 was joined to the CaMV 35S RNA promoter and transgenic tobacco plants were generated. However, neither transcripts nor a protein could be detected deriving from the W38/1 structural gene with this chimaeric construct in the transformants. Taken together, these data indicate that the genes contained in lambda clones W38/1 and W38/3 are not active in planta. PMID- 1888892 TI - High-level expression of a tobacco chitinase gene in Nicotiana sylvestris. Susceptibility of transgenic plants to Cercospora nicotianae infection. AB - Endochitinases (E.C.3.2.14, chitinase) are believed to be important in the biochemical defense of plants against chitin-containing fungal pathogens. We introduced a gene for class I (basic) tobacco chitinase regulated by Cauliflower Mosaic Virus 35S-RNA expression signals into Nicotiana sylvestris. The gene was expressed to give mature, enzymatically active chitinase targeted to the intracellular compartment of leaves. Most transformants accumulated extremely high levels of chitinase-up to 120-fold that of non-transformed plants in comparable tissues. Unexpectedly, some transformants exhibited chitinase levels lower than in non-transformed plants suggesting that the transgene inhibited expression of the homologous host gene. Progeny tests indicate this effect is not permanent. High levels of chitinase in transformants did not substantially increase resistance to the chitin-containing fungus Cercospora nicotiana, which causes Frog Eye disease. Therefore class I chitinase does not appear to be the limiting factor in the defense reaction to this pathogen. PMID- 1888894 TI - Sequence analysis of alfalfa (Medicago sativa) leghemoglobin cDNA and genomic clones. PMID- 1888893 TI - The expression of class I patatin gene fusions in transgenic potato varies with both gene and cultivar. AB - Patatin is a family of glycoproteins that contributes about 40% of the total soluble protein in tubers of potato (Solanum tuberosum L.). The protein is encoded by a multigene family of 50-70 genes which have been divided into classes I and II on the basis of sequence homology. The promoters of two class I genes, PS20 and PS3/27, were transcriptionally fused to beta-glucuronidase and transformed into the potato cultivars Desiree and Maris Bard. Examination of the expression levels in large populations of microtubers indicated that the PS20 promoter produced beta-glucuronidase activities 5-fold lower in Desiree than Maris Bard whereas the PS3/27 promoter showed similar levels in both cultivars. Furthermore, the relative expression levels from the two promoters were reversed in the two cultivars. The beta-glucuronidase enzyme activity was correlated with the mRNA level but not the copy number of the introduced gene. The implications for the use of patatin promoters in the genetic modification of tubers is discussed. PMID- 1888895 TI - Sequence analysis of a chalcone isomerase cDNA of Phaseolus vulgaris L. PMID- 1888896 TI - Analysis of the 5' flanking region responsible for the endosperm-specific expression of a rice glutelin chimeric gene in transgenic tobacco. AB - The 5' upstream region of the rice storage protein type II glutelin gene was examined for its regulatory function in transgenic tobacco. Chimeric genes containing 5' flanking regions of the glutelin gene transcriptionally fused to the beta-glucuronidase (GUS) reporter gene were introduced into the tobacco genome by Agrobacterium tumefaciens-mediated gene transfer. The chimeric genes were expressed specifically in developing seeds, as opposed to leaves and stems, of the transgenic tobacco. Histochemical analysis revealed that the GUS activity was restricted to the endosperm tissue. A deletion series of the 5' flanking region was created from position -1329 to -74 relative to the transcriptional initiation site and similarly examined in transgenic tobacco. Measurement of GUS activity of the seeds from the transgenic plants bearing the chimeric genes indicated that the region between positions -441 and -237 was required for the temporal and endosperm-specific expression of the GUS activity in tobacco. RNA analysis by northern blotting confirmed the importance of the -441 to -237 region. Addition of up to 888 bp to the -441 deletion resulted in little increase in GUS activity, although all constructs expressing the GUS gene showed a similar tissue and temporal regulation pattern. PMID- 1888898 TI - The interaction of CD4 with HIV-1 gp120. AB - CD4 is an integral cell surface glycoprotein that is able to enhance T cell specific antigen responses when it interacts with its physiological ligand, class II major histocompatibility (MHC) molecules. In addition, CD4 is a specific cell surface receptor for the human immunodeficiency virus-1 (HIV-1). Infection by HIV 1 is initiated by the binding of the envelope glycoprotein, gp120, to the first domain of CD4. The binding of CD4 to class II MHC is inhibited by gp120, one possible mechanism for immunosuppression in AIDS patients. In addition, the CD4/gp120 interaction may directly inhibit T cell function. Recently we have synthesized small molecules (CPFs) that specifically inhibit this interaction. CPFs bind to gp120 and prevent the binding of gp120 to CD4, and also inhibit the infectivity of HIV-1. PMID- 1888897 TI - Chloroplasts of Arabidopsis thaliana homozygous for the ch-1 locus lack chlorophyll b, lack stable LHCPII and have stacked thylakoids. AB - We are interested in the mechanism of insertion of proteins into the chloroplast thylakoid membrane and the role that accessory pigments may play in this process. For this reason we have begun a molecular analysis of mutant plants deficient in pigments that associate with thylakoid membrane proteins. We have characterized plants that are homozygous for the previously isolated, recessive mutation chlorina-1 (ch-1) of Arabidopsis thaliana. Despite the lack of chlorophyll b and light-harvesting proteins of photosystem II (LHCPII) near normal levels of LHCPII mRNA are found in the mutant, in contrast to LHCPII mRNA levels in carotenoid deficient mutants. The LHCPII mRNA of chlorina-1 plants can be translated in vitro so it is likely that LHCPII is not stable in ch-1 plants. Moreover, the thylakoid membranes of ch-1 plants remain appressed even though LHCPII levels are drastically reduced. PMID- 1888899 TI - Factors which cause tooth color changes ... protocol for in-office "power" bleaching. PMID- 1888900 TI - Dentist monitored bleaching: a combined approach. PMID- 1888901 TI - A comparative clinical study of two anticalculus dentifrices for efficacy in the inhibition and removal of surface stain and calculus. PMID- 1888902 TI - Chemical, optical, and physiologic mechanisms of bleaching products: a review. PMID- 1888903 TI - A predictable restorative Class V erosion technique. PMID- 1888904 TI - Removable telescopic frictional prosthesis. PMID- 1888905 TI - [Humanistic nursing care]. AB - The purpose of this study is to describe the degree of humanistic nursing care in different health care facilities as perceived by specialized nurses, registered nurses and licensed practical nurses. The problems of study are as follows: 1) What is the degree of humanistic nursing care as perceived by specialized nurses, registered nurses and practical nurses? 2) Do the nurses' perceptions of humanistic nursing differ between types of hospitals? The materials were gathered by a questionnaire which was compiled on the basis of the scale of humanistic nursing created and tested by Fenton (1987). In this scale, humanistic nursing is divided into four dimensions, including empathy, status equality, holistic selves, and shared decision-making and responsibility. The scale consisted of 70 statements describing patient and nursing staff behaviors, which were placed in a questionnaire with a 5-point Likert format. Fenton's scale was translated into Finnish as accurately as possible. Of the four dimensions of humanistic nursing care, the one-way analysis of variance revealed a statistically significant difference in the sum index for two dimensions and highly significant difference for one dimension by types of hospitals. The means of the equal status sum index differed in a statistically significant way among different hospitals. The sum index for status equality in nursing and the means computed for the statement measuring status equality in the nurses' own ward indicated that the nursing staff employed in central hospitals and health centers regard nursing as much more equal than those working in district hospitals. The central hospital nursing staff considered nursing care slightly more equal than those working in health centers. PMID- 1888907 TI - [Pressure sores frequently start with poor nursing technique]. PMID- 1888906 TI - [Professional nursing]. AB - One aim of Nursing Education is the Professionalization of Nursing. The characteristics of Nursing Professionalization are expertise, accountability and autonomy. The Nursing Education is a starting-point to expertise, what is a starting-point to accountability and autonomy. The professional Nursing is a more extensive concept than immediate nursing. It includes the Developing of Health Care System and the Providing of. PMID- 1888908 TI - [Prevention and care of pressure sores]. PMID- 1888909 TI - [The development of pressure sores]. PMID- 1888910 TI - [Care of pressure sores]. PMID- 1888912 TI - [The medical school at the city hospital in Berlin--Friedrichshain]. PMID- 1888911 TI - [Prevention of pressure sores]. PMID- 1888913 TI - [More satisfaction in nursing care activities. Interview by Kaarina Wilskman]. PMID- 1888914 TI - [Public health nurses as supporters of young people's self-esteem]. AB - Public Health Nurses are in a key position to support the self-esteem of young people and their families. Supporting people's self-esteem is significant for the welfare of the population. The purpose of this study was to investigate the connection between childhood experiences and young people's self-esteem and the type of assistance young people had received from public health nurses compared with their expectations in this respect. The population consisted of Finnish speaking students in the second form of upper secondary schools, students in their second year at vocational schools and first-term nursing students, all from Helsinki. A random sample of 461 pupils was taken. Public health nurses working with the young people in the sample totalled seven. Data were collected with the help of a questionnaire in March 1986. The response rate was 100%. The research findings showed that there is a connection between a person's childhood experiences and self-esteem. The more support young people had received from their parents, the brighter their perception of their childhood and the better their chances of developing high self-esteem. The more a public health nurse had supported young people's self-esteem, the better they viewed the visits to as having met their expectations and the more ready they were to accept the public health nurse's help, which they also regarded as important. A public health nurse's support helped to strengthen young people's self-esteem. The findings will be used to increase public health nurses' opportunities to support the self esteem of children, young people and their parents. Public health nurses' capacities to do this should be increased through education and supervision. PMID- 1888915 TI - [Public health nursing's role in a crisis stage: people-oriented functions are obsolete]. AB - The nurses and the public health nurses identified mostly individuals as the focus of their service although also families and groups are increasingly receiving services. Orientation towards communities or environments is rather rare. The modes of nursing practice of nurses differentiated from each other quite a lot. On the basis of the results two main modes had been identified: organization oriented and people oriented mode. The organization oriented made is somewhat stereotyped, rather guided by rules and regulations than by the needs of people. The people oriented mode is based on the needs of clients. The needs are being assessed openly and by exploring the situation. Client-centred objectives are being established more often and the interventions are better identified than in the organization oriented mode. The interventions are focused to support the resources of the clients f.e. their own thinking processes and other abilities. On the basis of the interviews it seems to be that nursing practice is in the middle of a transition period. The accountability for one's practice is being gradually accepted. Nursing practice is developing to a more individual direction and the viewpoints of people will be better understood. PMID- 1888916 TI - [The nature of health in nursing advanced--is discussion on nursing activities in health needed?]. AB - Nurses promoting patient's health--is there a need to discuss the concept of health in nursing? The concept of health has been studied from different points of view in order to determine what health is. The nature of health is problematic and value based. In nursing where the health and wellbeing of patient is of interest to the practice, there is a need to become aware of what kind of health nurses are promoting. Does health promotion mean the same as disease prevention or does health have any positive content? There is need to get more information about health by studying it from different perspectives, for instance as perceived by clients. Also in nursing practice nurses should discuss the purpose of their action. PMID- 1888917 TI - [Young men's attitude to life and self-evaluation of the basis for development of health care activities]. AB - This article describes the results of a study which seeks to ascertain the extent to which young men feel themselves to be in control of their lives as well as to obtain insights which can be of use in developing methods for promoting good health. The target group consisted of men thirty years of age or younger employed by the state in health district of the city of Oulu. A questionnaire was used to collect the data from a random sample of 150 men. The percentage of response was 70%. 94% of the respondents were employed and almost half (48%) had graduated from upper secondary school resulting in a sample population of above average education. In general the young men who answered the questionnaire had a positive attitude upon their lives and their futures. They see themselves as having obtained satisfaction in their lives and having achieved their goals as well as having succeeded in having some control upon the course of their lives. The majority of respondents were satisfied in their work. They also indicated satisfaction with their relationships with friends and family. White-collar workers tended to express more satisfaction with their lives than did blue-collar workers and graduates of upper secondary school tended to indicate a greater sense of reward and recognition in their lives than did those who had not gone beyond comprehensive school. Almost all of the respondents described good health in terms of physical and mental well-being. Only four defined good health solely in terms of the absence of illness. PMID- 1888918 TI - [Nursing care of patients with AIDS is a holistic nursing process]. AB - Every nurse should be prepared to meet a person with HIV-infection. Nursing care of people with AIDS is a challenge because it is a holistic nursing process of a person. After diagnosing a HIV-infection a person will be in a crisis. If a nurse is familiar with the process of a crisis, he/she can better understand and support the person. With empathy, therapeutic attitude and by recognizing own reactions a nurse will be able to meet the needs of the patients. The nursing plan helps a nurse to plan, to see the problems, to implement and to evaluate the nursing process of the patient with AIDS. The aim of the nursing process is to react to the unique needs of the patient with the HIV-infection. To be able to grow as a human being and as a professional nurse, one needs education about HIV infection and its specific areas. During discussions and consultations, nurses are able to share their feelings and reactions caused by HIV-infection. PMID- 1888919 TI - [Changes in health services]. PMID- 1888920 TI - The American health care predicament. PMID- 1888921 TI - "Brittle" diabetes. PMID- 1888922 TI - What do patients want? PMID- 1888923 TI - Total knee replacement. PMID- 1888924 TI - American sex survey cancelled. PMID- 1888925 TI - Effect of a fetal surveillance unit on admission of antenatal patients to hospital. AB - OBJECTIVE: To analyse the effect of a fetal surveillance unit, which undertakes a wide range of maternal and fetal tests on an outpatient or inpatient basis, on the number and length of antenatal hospital admissions. DESIGN: A comparison of the number and length of antenatal admissions six months before and five months after the opening of the unit on 1 July 1990. MAIN OUTCOME MEASURES: Admission rate, antenatal bed occupancy, and interval from admission to discharge or delivery. RESULTS: The antenatal bed occupancy rate fell by 22% from 174/100 deliveries during the six months before the unit was opened to 136/100 deliveries in the five months after it was opened. The difference in distribution of lengths of admission after the unit was opened from before was highly significant (Mann Whitney test = 5.14, n = 752 and 679; p less than 0.0001), and this was due to shorter intervals from admission to discharge and from admission to delivery. In contrast, the antenatal admission rate did not change significantly (50/100 deliveries v 49/100 deliveries). There was no significant change in the stillbirth rate (6/1294 births v 8/1372 births; difference between rates = 0.0012, 95% confidence interval-0.0043 to 0.0067). CONCLUSION: Obstetricians are more prepared to discharge antenatal patients from hospital and, similarly, admit patients for delivery rather than for assessment if the patients are reliably monitored on an outpatient basis. If this change in practice is sustained substantial financial and social benefits will result as well as improvements in organisation, audit, teaching, and research. PMID- 1888926 TI - Prevalences of diabetes and cardiovascular disease risk factors in Hindu Indian subcommunities in Tanzania. AB - OBJECTIVES: To seek differences in the prevalence of diabetes mellitus and other coronary heart disease risk factors, and to identify factors associated with these differences within a Hindu Indian community. DESIGN: Population based cross sectional survey. SETTING: Dar-es-Salaam, Tanzania. SUBJECTS: Of 20 Hindu subcommunities categorised by caste in Dar-es-Salaam, seven were randomly selected. 1147 (76.7%) of 1495 subjects aged 15 or over participated. MAIN OUTCOME MEASURES: Blood glucose concentrations (fasting and two hours after oral glucose loading), serum total cholesterol and serum triglyceride concentrations, blood pressure, and height and weight. RESULTS: The subcommunities differed substantially in socioeconomic characteristics and lifestyle. Overall, 9.8% of subjects (109/1113) had diabetes, 17.0% (189/1113) impaired glucose tolerance, 14.5% (166/1143) hypertension, and 13.3% (151/1138) were obese. The mean fasting blood glucose concentration was 4.9 mmol/l, the blood glucose concentration two hours after oral loading (75 g) 6.0 mmol/l, the total cholesterol concentration 4.9 mmol/l, the serum triglyceride concentration 1.4 mmol/l, and body mass index (weight/height: kg/m2) 24.3. Systolic and diastolic blood pressures were 121 and 77 mm Hg respectively. There were important intercommunity differences even after standardisation for age, sex, and body mass index--for example, in mean fasting blood glucose concentration (range 4.5 (Jains) to 5.9 mmol/l (Patels)), serum total cholesterol concentration (range 4.5 (Jains) to 6.2 mmol/l (Suthars)), systolic blood pressure (range 110 (Limbachias) to 127 mm Hg (Bhatias)), and prevalences of diabetes (range 3.4% (3/87 Limbachias) to 18% (20/111 Navnats)) and hypertension (range 5.7% (5/87 Limbachias) to 19.4% (43/222 Bhatias). Variables which showed significant linear correlation with subcommunity variations were entered into a multiple regression model. Intercommunity variations persisted. The Limbachia and Jain communities had the lowest prevalence of and mean values for coronary heart disease risk factors and the Bhatia and Patel communities had the highest. CONCLUSIONS: In this series intercommunity variations in disease and risk factors might have been related to genetic, dietary, socioeconomic, and lifestyle differences but could not be explained by the characteristics studied. Studies of Indian subcommunities are warranted to confirm and extend these descriptive findings and explore the genetic basis of diabetes. Communities of Indian origin should not be perceived as homogeneous. PMID- 1888928 TI - Outcome of brittle diabetes. PMID- 1888927 TI - Serum cholesterol concentration and coronary heart disease in population with low cholesterol concentrations. AB - OBJECTIVE: To examine the relation between serum cholesterol concentration and mortality (from coronary heart disease and from other causes) below the range of cholesterol values generally seen in Western populations. DESIGN: Prospective observational study based on 8-13 years of follow up of subjects in a population with low cholesterol concentrations. SETTING: Urban Shanghai, China. SUBJECTS: 9021 Chinese men and women aged 35-64 at baseline. MAIN OUTCOME MEASURE: Death from coronary heart disease and other causes. RESULTS: The average serum cholesterol concentration was 4.2 mmol/l at baseline examination, and only 43 (7%) of the deaths that occurred during 8-13 years of follow up were attributed to coronary heart disease. There was a strongly positive, and apparently independent, relation between serum cholesterol concentration and death from coronary heart disease (z = 3.47, p less than 0.001), and within the range of usual serum cholesterol concentration studied (3.8-4.7 mmol/l) there was no evidence of any threshold. After appropriate adjustment for the regression dilution bias, a 4 (SD 1)% difference in usual cholesterol concentration was associated with a 21 (SD 6)% (95% confidence interval 9% to 35%) difference in mortality from coronary heart disease. There was no significant relation between serum cholesterol concentration and death from stroke or all types of cancer. The 79 deaths due to liver cancer or other chronic liver disease were inversely related to cholesterol concentration at baseline. CONCLUSION: Blood cholesterol concentration was directly related to mortality from coronary heart disease even in those with what was, by Western standards, a "low" cholesterol concentration. There was no good evidence of an adverse effect of cholesterol on other causes of death. PMID- 1888929 TI - Reuse of disposable plastic insulin syringes. PMID- 1888930 TI - Effects of parathyroid hormone on delayed renal allograft function. PMID- 1888931 TI - Assessment of pain after subcutaneous injection of erythropoietin in patients receiving haemodialysis. PMID- 1888932 TI - Why patients consult and what happens when they do. AB - OBJECTIVE: To study patients' perceptions of why they consulted the doctor, how ill they thought they were, and what happened in the consultation. To compare patients' perceptions before and after the consultation and to compare these perceptions with those of the doctor. DESIGN: Patients filled in a questionnaire before and after the consultation. The doctor filled a questionnaire in after the consultation. SETTING: Three general practices in Bedfordshire and one in Hertfordshire. PATIENTS: 500 consecutive patients consulting in each practice. MAIN OUTCOME MEASURES: Changes in patients' perceptions and differences between the perceptions of patients and doctors. RESULTS: Doctors perceived patients to be less ill than the patients themselves did. Patients from social classes IV and V and children perceived themselves to be more ill than the average. Patients perceived themselves to be less ill after the consultation. A third of patients attended because doctors had told them to, and a quarter of patients had already tried to treat their problem themselves when they attended the consultation. Doctors' perceptions of the consultation emphasised listening, supporting, and giving advice. Patients' perceptions emphasised prescribing, reassuring, and referring to a consultant. Doctors perceived that they listened, examined, and gave advice less to social classes IV and V than to social classes I, II, and III and gave explanations more often to men than to women. Patients perceived external factors rather than lifestyle factors as being more important in causing their problems. CONCLUSION: Doctors' perceptions of patients' problems differed from those of patients expressed both before and after their consultation. Doctors' and patients' perceptions also differed about the consultation itself. The consultation reassured some patients. PMID- 1888934 TI - Homosexuality and parenthood. PMID- 1888933 TI - General practitioners' views on quality specifications for "outpatient referrals and care contracts". AB - OBJECTIVE: To ascertain general practitioners' views about which quality specifications should be included in contracts for hospital care. DESIGN: In depth interview study and postal survey. SETTING: General practitioners in City and Hackney Health District. SUBJECTS: Fourteen doctors were interviewed in depth; 77 of 131 doctors (59%) returned postal questionnaires. MAIN OUTCOME MEASURE: Rating of listed quality specifications. RESULTS: The most popular items which doctors thought should be included in contracts by April 1991 related to the availability of patients' notes in outpatient clinics, respect shown to general practitioners in telephone communications with hospital doctors, supply of medicines after discharge, patient management plans for general practitioners, the earlier arrival of discharge slips, the type of hospital doctor to see new outpatients, and the unnecessary duplication of investigations. CONCLUSIONS: A high premium was attached by general practitioners to effective organisation, effective communication between primary and secondary sources of care, and effective communication with patients. PMID- 1888935 TI - First steps towards a strategy for health. PMID- 1888936 TI - Health costs of the Gulf war. PMID- 1888937 TI - HIV testing of patients with end stage renal failure. PMID- 1888938 TI - Management in the NHS. PMID- 1888939 TI - A tax on infertility? PMID- 1888940 TI - Zidovudine after occupational exposure to HIV. PMID- 1888941 TI - Same day testing for HIV. PMID- 1888942 TI - Incidence of HIV infection among homosexual men. PMID- 1888943 TI - The health of the nation. PMID- 1888944 TI - Availability of cadaver organs for transplantation. PMID- 1888945 TI - Ethics, commerce, and kidneys. PMID- 1888946 TI - Cervical samplers. PMID- 1888947 TI - Failure to encourage breast feeding. PMID- 1888948 TI - Future of mental health services. PMID- 1888949 TI - Prioritizing equipment inspections. PMID- 1888950 TI - Joint Commission changes and trends for equipment managers. Interview by Mary Beth Hatem. PMID- 1888951 TI - From quality assurance to quality improvement: a guide to the Joint Commission's change in emphasis. PMID- 1888952 TI - Clinical engineering participation in hospital technology assessment. PMID- 1888953 TI - Pacemakers, past-makers, and the paced: an informal history from A to Z (Aldini to Zoll) PMID- 1888954 TI - Apnea monitoring basics. PMID- 1888955 TI - Psychiatrists and citizens. PMID- 1888956 TI - Personality as a vulnerability factor to depression. AB - One hundred and forty non-depressed primiparous women in a stable relationship completed two personality measures (the EPI and the IPSM) antenatally, and were then assessed for depression at several times post-natally. The risk of depression at six months was increased up to tenfold by high interpersonal sensitivity and threefold by high neuroticism. When previously depressed women were excluded from analyses, high interpersonal sensitivity and, to a lesser extent, high neuroticism were still associated with an increased risk of being depressed. Interpersonal sensitivity, as measured, is suggested as a refined personality risk factor to both the onset and recurrence of depression. PMID- 1888957 TI - Early sexual abuse and clinical depression in adult life. AB - Sexual abuse in childhood and adolescence was studied in 286 working-class mothers living in Islington, who were contacted on three occasions over a two year period. The sample was collected primarily to study current vulnerability factors in the onset of depression, but childhood measures were also included to look at longer-term risk factors. Twenty-five women - 9% of the sample - reported sexual abuse involving physical contact before age 17 and, of these, 64% had case depression in a three-year period (which included the year before first interview). While such abuse was related to other earlier stressful experiences such as parental indifference, violence to the child and institutional stay, it was associated with an increased risk of depression over and above these factors. Sexual abuse before age 17 also related to having been divorced/separated or never having married/cohabited. PMID- 1888958 TI - Outcome of bipolar disorder on long-term treatment with lithium. AB - The long-term treatment outcome of 248 bipolar patients in an out-patient lithium programme was assessed. Over half of the patients (138 or 56%) had no affective episodes in the year observed. Patients were divided into outcome groups according to GAS scores: the outcome for 40% of patients was good, for 41% fair, and for 19% poor. More frequent psychiatric admissions before starting lithium treatment was the best predictor of poor outcome, followed by a negative affective style in the family and lower social class. Current alcohol and drug abuse was associated with poor outcome. Although familial and psychosocial factors were significantly associated with outcome, the findings suggest there may be inherent differences in the pathophysiology of bipolar disorder reflected in an increased frequency of episodes which account for a large variance in lithium treatment outcome. PMID- 1888959 TI - The impact of political change in eastern Europe on behavioural sciences and psychiatry. PMID- 1888960 TI - Correlation of negative symptoms in schizophrenia with frontal lobe parameters on magnetic resonance imaging. AB - Among 24 chronic schizophrenic patients, the 10 with high ratings for negative symptoms had significantly higher left-frontal: temporal-cortical T2 ratios. This finding was unrelated to age, dose of medication, length of illness or handedness. No T1 or T2 changes were found to be associated with positive symptoms or tardive dyskinesia in the regions examined. PMID- 1888961 TI - Symptoms of post-traumatic stress disorder in Falklands veterans five years after the conflict. AB - A group of 64 Falklands war veterans who were still serving in the British Army were studied and compared with a group of matched controls. Half the veterans reported some symptoms of post-traumatic stress disorder, and 22% were rated as having the complete PTSD syndrome. Presence of the symptoms was associated with intensity of combat experience and the retrospective report of emotional difficulties in the initial period on return from the war. PMID- 1888962 TI - Psychotherapy 2000. Some predictions for the coming decade. PMID- 1888963 TI - Outcome for elderly depressives. PMID- 1888964 TI - Lithium education programme. PMID- 1888965 TI - 'The disease concept of alcoholism'. PMID- 1888966 TI - Double blind acceptance. PMID- 1888967 TI - Ordering thoughts in thought disorder. PMID- 1888968 TI - Anabolic steroid use outside competition. PMID- 1888969 TI - Treatment-resistant depression. PMID- 1888970 TI - Psychiatry and post-traumatic stress disorder. PMID- 1888971 TI - Access to Health Records Act, 1990. PMID- 1888972 TI - Chloroquine-induced mania. PMID- 1888973 TI - Catatonia and NMS. PMID- 1888975 TI - On the therapeutic value of Indian hemp, 1891. PMID- 1888974 TI - Amitriptyline in clozapine-induced sialorrhoea. PMID- 1888977 TI - The evolution of the British Journal of Psychiatry. PMID- 1888976 TI - The human brain and political behaviour. PMID- 1888978 TI - The history of 'nervous disorders' from 1600 to 1840, and a comparison with modern views. AB - In the 18th century the main varieties of nervous illness - hypochondria, hysteria, the spleen, the vapours and dyspepsia - became included under the general term 'nervous disorders'. When no physical disorder of the nerves could be detected in such conditions, the hypothesis of nervous disorder was replaced by the more vague concept of 'nervous temperament'. The fact that there is still no evidence of pathological change in such cases continues to expose physicians to the alternative hypothesis of a purely psychological cause. The modern era in our understanding of the nervous system may be said to date from 1843 when Du Bois Reymond showed the electrical nature of nervous conduction. The publication of Jorden's Briefe Discourse in 1603 may be taken to represent the start of a discrete period (1600 to 1840) in the history of neurotic illness. PMID- 1888979 TI - The founding of psychiatric nurse training and its aftermath. AB - The first national training scheme for attendants upon the insane began in 1891. The Medico-Psychological Association considered this initiative as essential if asylums were to have therapeutic credibility and recruit high-quality attendants. The initiative failed because poor pay and conditions of service were obstacles to recruitment and better standards of care. The Association then sought to integrate asylum and general nursing, leading to a double sense of betrayal on the part of the asylum nurses. They felt betrayed by the failure of the training scheme to improve their career structure and by the threat to their jobs posed by the proposed merger with general nurses. They responded by unionisation, so that two decades after the introduction of training, its only major effect had been to politicise nurses and engage them in disputes with their hospital superintendents and employing authorities. Training raised expectations in the attendants which neither the Association nor the institutions had intended to satisfy, and it was not seen by attendants as of benefit either to them or to patients. PMID- 1888980 TI - Twentieth-century influences on the development in Britain of services for child and adolescent psychiatry. AB - Modern comprehensive multidisciplinary mental-health services for children and adolescents have four origins: psychology from 1890, psychoanalysis from 1906, the child-guidance movement from 1920, and the children's departments of psychiatric teaching hospitals from 1930. Post-war changes in society and reform, especially the NHS Act 1946, contributed to rapid development of services and an increasingly wide range of sophisticated therapeutic interventions; professional and interdisciplinary associations and trans-Atlantic exchange were also influential. In the last three decades a succession of official inquiries, reports, legislation and reorganisations have had a damaging effect. Children and their services have been prey to causes celebres, fashion and the exaggerated fads and foibles of the media and politicians; they have thrived best when society and their carers were tolerant, and loving, sought good qualities to augment, not evil to exorcise, and succeeded in balancing structure and control with flexibility and freedom to grow. Planners should review the past before acting. PMID- 1888981 TI - The Surrey County Lunatic Asylum (Springfield). Early years in the development of an institution. AB - In the mid-19th century, the Commissioners in Lunacy continued the direction of the earlier reform movements, but depended upon local magistrates for the execution of their ideas. The early development of a single county asylum is described from its beginnings, as are some of the personalities involved. PMID- 1888982 TI - The Holocaust and German psychiatry. PMID- 1888983 TI - Measurement in psychiatry. PMID- 1888984 TI - Drinking, thirst and water intoxication. AB - Drinking is an activity determined partly by oropharyngeal stimulation and gastrointestinal sensations as well as biochemical changes, and thirst need not be involved. It is sometimes disturbed in mania or depression. Overdrinking (polydipsia) is common in long-stay in-patients, but only gives rise to water intoxication when there is a variable functional renal abnormality such as SIADH causing water retention. In contrast, in affective disorders, disturbance of sodium retention may be seen, possibly representing failure of nervous vascular control as part of the mental illness. PMID- 1888985 TI - Pathways to psychiatric care in South Manchester. AB - Of 250 patients newly referred to the mental illness services of South Manchester, almost two-thirds were referred directly by their GPs; a further third were referred by hospital doctors. Non-medical sources of referral accounted for only 2% of new cases. Patients with somatic problems had the longest interval between seeking care and referral to the psychiatric services. Being employed was associated with a longer delay before seeking care; among women, those living with their husbands or children had longer total intervals between the onset of the problem and arrival at the psychiatric services. PMID- 1888986 TI - Affects as central organising and integrating factors. A new psychosocial/biological model of the psyche. AB - A new psychosocial/biological model of the psyche is proposed, in which the affects play a central role in organising and integrating cognition. The psyche is understood here as a complex hierarchical structure of affective/cognitive systems of reference (or 'programmes for feeling, thinking, and behaviour'), generated by repetitive concrete action. These systems store past experience in their structure, and provide the functional basis for further cognition and communication. Affects endow these programmes with a specific qualitative value (such as motivation), connect cognitive elements synchronically and diachronically, and contribute to their storage and mobilisation according to context. They also participate in differentiating cognitive systems at higher levels of abstraction. These assumptions are supported by recent findings on the role of the limbic and hypothalamic system for the regulation of emotion, on neuronal plasticity, and on the phenomenon of state-dependent learning and memory. Refutable hypotheses are formulated for further research on the interaction of emotion and cognition. PMID- 1888987 TI - Effects of convulsants on handling-induced convulsions in mice selected for ethanol withdrawal severity. AB - Withdrawal seizure-prone (WSP) mice were genetically selected to express severe handling-induced convulsions (HIC) upon cessation of chronic ethanol vapor inhalation. The HIC is a sensitive measure of CNS excitability, and the current paper compares the effects of eleven convulsant drugs on the HIC in WSP and WSR (withdrawal seizure-resistant) mice, the latter selected for minimal alcohol withdrawal HIC. If WSP and WSR mice were differentially sensitive to a subset of the tested drugs, a common mechanism of action for that subset would imply that genes influencing that mechanism were important in determining ethanol withdrawal severity. All drugs significantly enhanced HIC in WSP mice. The magnitude of enhancement was small for N-methyl-D-aspartate (NMDA), kainic acid, BAY K 8644, Ro 15-4513, and strychnine; greater enhancement in WSP mice was seen after nicotine, and the direct and indirect gamma-aminobutyric acid (GABA) antagonists bicuculline, 3-mercaptopropionic acid, picrotoxin, t-butylcyclophosphorothionate (TBPS), and pentylenetetrazol. Only two drugs, picrotoxin and pentylenetetrazol, had a marked effect on WSR mice: maximal effect of these drugs was equivalent in WSP and WSR mice. However, picrotoxin and pentylenetetrazol were more potent in WSP than in WSR mice. Three other GABA antagonists, bicuculline, 3 mercaptopropionic acid, and TBPS, had a very small effect in WSR mice: these drugs also seemed to be more potent in WSP than in WSR mice. For all other tested drugs, maximal effect in WSP mice was much greater in WSP than in WSR mice.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1888988 TI - Insular cortex stimulation produces lethal cardiac arrhythmias: a mechanism of sudden death? AB - The rat posterior insular cortex has recently been shown to possess cardiac chronotropic organization and therefore may be involved in cortical mechanisms of sudden death. In order to assess the potential of this region for cardiac arrhythmogenicity, phasic microstimulation of tachycardia zones was undertaken in the urethane-anesthetized rat. The insular stimulus was triggered by the R wave of the electrocardiogram (ECG) and delayed so that resultant putative cardiac sympathetic nerve activity would be synchronous with the T wave of the ECG. This resulted in increasing degrees of heart block leading to escape rhythms, ventricular ectopics and ultimately death in asystole. Heart block was associated with elevated plasma norepinephrine levels and myocardial damage. Such effects have not been previously demonstrated for a cortical site. These data suggest that pathophysiological activation of the insular cortex by stroke, epileptic seizure, or under conditions of severe emotional stress could predispose to ECG changes, cardiac arrhythmias and sudden death. PMID- 1888989 TI - Functional brain asymmetry and lymphocyte proliferation in female mice: effects of right and left cortical ablation. AB - Brain immunomodulation may be lateralized as evidenced by two experimental approaches. Using a behavioral paradigm, we have reported an association between asymmetrical brain function and lymphocyte reactivity in mice selected for right- and left-paw preference. Left-handed mice, in comparison to right-handers, exhibit higher mitogen-induced T-lymphocyte proliferation. Using a cortical lesion paradigm in mice, it has been previously shown that each hemicortex modulates in opposite directions lymphocyte reactivity. In these experiments, the role of the brain cortex in the association between paw preference and immune reactivity was assessed by studying mitogen-induced lymphoproliferation in left- and right-handed mice after right or left-cortical ablation. The difference in T lymphocyte responsiveness between right- and left-handed mice persisted after right lesions but was abolished after left lesions. This immunological effect of left cortical ablation is hypothesized to involve the hypothalamic dopaminergic neurons. PMID- 1888990 TI - Characterization of muscarinic receptor subtype of rat eccrine sweat gland by autoradiography. AB - The muscarinic cholinergic receptor of rat eccrine sweat gland was characterized using quantitative autoradiography and [3H]QNB as radioligand. The distribution of radioligand was maximal in the secretory coil. Autoradiographic competition binding studies were performed using selective antagonists to M1 (pirenzepine), M2 (AF-DX 116), and M3 (4-DAMP) and the classical nonselective antagonist atropine. pKi for pirenzepine, AF-DX 116, 4-DAMP, and atropine was 6.58, 5.47, 8.50, and 8.66 respectively indicating that the eccrine sweat gland muscarinic receptor was predominantly M3. PMID- 1888991 TI - Frequency dependence of cat vestibulo-ocular reflex direction adaptation: single frequency and multifrequency rotations. AB - Vertical and horizontal vestibulo-ocular reflex (VOR) eye movements were recorded in alert cats during horizontal rotation in total darkness before and after a 2 h vestibulo-ocular reflex direction adaptation procedure. Adaptation stimuli were whole body horizontal vestibular rotation coupled to synchronous vertical optokinetic motion. The waveform of the adaptation stimuli was either a sinusoid at 0.05, 0.1, 0.25, 0.5, or 1 Hz, or a sum of sinusoids containing 0.2, 0.3, 0.5, 0.7, 1.1, and 1.7 Hz. Exposure to single frequency stimuli produced adaptive vertical VOR with a gain that was greatest near the training frequency; adaptive VOR phases were advanced below, accurate at, and lagged above the training frequency. Exposure to the multifrequency waveform produced a uniform modest increase in gain across frequencies, with accurate adaptive VOR phase. PMID- 1888992 TI - Changes in filipin-sterol binding in the rat cingulate cortex after the administration of antidepressant drugs. A freeze-fracture study. AB - The amount of cholesterol in cell membranes of cingulate cortex nerve cells from rats treated with Imipramine (tricyclic antidepressant drug) or mianserin (non tricyclic antidepressant) was investigated using filipin-sterol binding and freeze-fracture. The number of filipin-sterol complexes decreased within membranes of neurons from cingulate cortex chronically treated with imipramine or mianserin. These results suggest that the decreased content of cholesterol causes the cell membrane to become more fluid. This increased fluidity of the cell membrane may play an important role in regulating the interaction of transmitters and drugs with their membrane receptors. PMID- 1888993 TI - Intrathecal serotonin attenuates the pressor response to static contraction. AB - We tested the hypothesis that intrathecal injection of serotonin onto the lumbosacral spinal cord of chloralose-anesthetized cats attenuates the pressor response to static contraction of the triceps surae muscles. Serotonin (10 micrograms) significantly attenuated the contraction-induced reflex increases in mean arterial pressure but not in ventilation. This attenuation of the reflex pressor response to static contraction by serotonin was prevented by prior intrathecal injection of mianserin hydrochloride, a serotonergic receptor antagonist. In addition, the reflex pressor response to contraction was significantly attenuated by intrathecal injection of carboxamidotryptamine maleate, a 5-HT1 agonist but not by DOI-hydrochloride, a 5-HT2 agonist. We conclude that stimulation of 5-HT1 receptors in the lumbosacral spinal cord attenuates the reflex pressor response to static muscular contraction. PMID- 1888994 TI - The effects of amphetamine preexposure on electrical kindling of the hippocampus and related transfer phenomena. AB - Earlier research has established that repeated amphetamine administration can interact synergistically with the processes responsible for the genesis of kindled seizures after intermittent electrical stimulation of the amygdala. In this study, the effects of amphetamine preexposure on primary hippocampal kindling, secondary kindling of the contralateral amygdala, and rekindling of the original hippocampal focus were evaluated. It was shown that amphetamine treatment did not modify kindling rates when electrodes were situated in the dorsal hippocampus. However, transfer kindling of the contralateral amygdala evolved after fewer afterdischarges, and rekindling of the dorsal hippocampus progressed significantly faster in amphetamine-pretreated animals. The effects of amphetamine on ventral hippocampal kindling were also determined, and it was found that although epileptogenesis developed more rapidly relative to the dorsal region of this structure, kindling rates were not affected by amphetamine preexposure. These results were related to the possibility that the amygdala might have a unique function in the relationship between kindling- and stimulant induced sensitization effects. PMID- 1888995 TI - GABA release in the zona incerta of the sheep in response to the sight and ingestion of food and salt. AB - In order to establish which neurotransmitters may influence the activity of zona incerta neurones in the sheep which respond selectively to the sight or ingestion of food, we have measured the release of amino acid and monoamine neurotransmitters from this region using microdialysis sampling. Co-ordinates for the placement of microdialysis probes in regions of the zona incerta where cells respond to the sight or ingestion of food were first established by making single unit extracellular recordings. When animals were food-deprived results showed that release of gamma-aminobutyric acid (GABA) was increased in response to the sight and ingestion of food but not of aspartate, glutamate, taurine, noradrenaline, dopamine or serotonin. This release of GABA was absent when the animals were shown non-food objects or saw or ingested salt solutions. When the same animals were physiologically sodium-depleted GABA release was evoked by the sight and ingestion of salt solutions and release following the sight and ingestion of food was significantly reduced. These results provide further evidence that GABA is an important neurotransmitter in neural circuits controlling the regulation of food intake. PMID- 1888996 TI - Influence of substantia innominata neuronal activity on neocortex neuronal reactions during conditioned reflex. AB - Impulse activity of substantia innominata (SI) and motor cortex neurons was studied in cats during conditioned placing with food reinforcement. It was shown that SI neurons have been activated first directly by sound stimuli and later by food reward. Stimulation of SI did not change the background activity of neocortex neurons but promoted the modulation of impulse response to conditioned stimuli. The modulating effect of the SI has a mainly excitatory character, that manifested itself either in a change and increase of the impulse responses of cortical neurons which responded initially to sound stimuli, or in the appearance of impulse responses in those neurons which showed no initial reaction to conditioned sound stimuli. PMID- 1888997 TI - Do adenosinergic substrates mediate methylxanthine effects upon reinforcement thresholds for electrical brain stimulation in the rat? AB - Caffeine and other methylxanthines elevate reinforcement threshold for electrical brain stimulation with an order of potency suggesting that the effect is mediated by antagonism of adenosine A2 receptors. The purpose of this study was to evaluate further the possible mechanism by which caffeine and other methylxanthines elevate reinforcement thresholds for ICSS. Drugs known to affect adenosinergic transmission in predictable ways, adenosine receptor agonists and antagonists and benzodiazepine agonists and inverse agonists, were tested to determine their effect upon reinforcement threshold. Both the selective A1 adenosine agonist, R(-)-PIA, and the non-selective A1/A2 adenosine agonist NECA failed to alter reinforcement thresholds, as did CGS 15943, a potent non-xanthine non-selective adenosine receptor antagonist. Chlordiazepoxide, a benzodiazepine agonist, lowered reinforcement thresholds and FG 7142, a benzodiazepine inverse agonist, elevated reinforcement thresholds, perhaps corresponding to their anxiolytic and anxiogenic subjective effects in humans. However, another benzodiazepine agonist, midazolam and another inverse agonist, beta-CCE, did not alter reinforcement thresholds. These results fail to support a general role for adenosinergic systems in the threshold-elevating effect of methylxanthines. PMID- 1888998 TI - Early neural grafts transiently reduce the behavioral effects of radiation induced fascia dentata granule cell hypoplasia. AB - X-irradiation of the neonatal rat hippocampus produces a selective hypoplasia of fascia dentata granule cells, locomotor hyperactivity, perseverative movements and deficits in passive avoidance. We previously reported that transplantation of fetal hippocampal tissue into the adult (age = 182 +/- 4 days) brain produced a partial recovery of these behavioral deficits. Since graft/host interconnections are more prominent when transplants are conducted soon after radiation-induced hippocampal damage, in this study we transplanted hippocampal or cerebral cortex neurons when host rats were 33 +/- 5 days of age (i.e. only 16 days after radiogenic brain damage). Behavioral evaluations were conducted 80 and 182 days after transplantation or surgical control procedures. In the first test series only, selective components of locomotion (e.g. stereotypy and total distance traveled) and perseverative turning (e.g. mean bout length and turning speed topography) were normalized by the hippocampal grafts. Radiation-induced changes in passive avoidance were less prominent in these studies than in past experiments. Still, transplantation of hippocampal tissue improved performance on this learning task as well. Cerebral cortex grafts did not produce reliable improvements in most behavioral measures. These data suggest that hippocampal grafts placed soon after X-ray induced fascia dentata hypoplasia reduce a broad range of behavioral deficits. However, these benefits are transient and, for the most part, depend on the use of transplant tissues homologous with those damaged. PMID- 1888999 TI - Spinal serotonin receptors mediate descending facilitation of a nociceptive reflex from the nuclei reticularis gigantocellularis and gigantocellularis pars alpha in the rat. AB - Electrical stimulation in the nucleus reticularis gigantocellularis (NGC) and gigantocellularis pars alpha (NGC alpha) produces facilitation and/or inhibition of spinal nociceptive transmission in behavioral and electrophysiological studies. The present study examined spinal neurotransmitter receptors mediating descending facilitation from the NGC/NGC alpha. As previously demonstrated, electrical stimulation in the NGC/NGC alpha at low intensities (approximately equal to 10 microA) produced facilitation and at greater intensities (approximately equal to 38 microA) inhibition of the tail-flick (TF) reflex. Intrathecal pretreatment with the non-selective serotonin (5-HT) receptor antagonist methysergide attenuated or completely abolished facilitation of the TF reflex produced by electrical stimulation in the NGC/NGC alpha; intrathecal pretreatment with atropine, phentolamine, naloxone or mecamylamine was without effect on stimulation-produced facilitation. Descending inhibition from the NGC/NGC alpha produced by electrical stimulation was attenuated or completely abolished by bilateral transection of the dorsolateral funiculi (DLF) of the cervical spinal cord. Descending facilitation produced by electrical stimulation, however, was unaffected or enhanced following DLF transections. Glutamate microinjections (1.7 nmol/0.17 microliters) into the NGC/NGC alpha produced a rapid, repeatable and short-duration facilitation of the TF reflex in rats with bilateral DLF transections and such facilitation was attenuated by intrathecal pretreatment with methysergide, but not atropine, xylamidine (5-HT2 selective receptor antagonist) or MDL-72222 (5-HT3 selective receptor antagonist). These findings suggest that facilitation of the TF reflex from the activation of the cell bodies in the NGC/NGC alpha is mediated by a descending serotonergic pathway traveling in the ventrolateral funiculi and by spinal 5-HT1 receptors. PMID- 1889000 TI - Visual stimulation reduces EEG activity in man. AB - Data are presented which show that background electric activity of the human brain is reduced by visual stimulation. Occipital EEG amplitude decreases 5-15% for all frequencies analyzed (0.2-40 Hz) upon pattern stimulation. The reduction is stimulus-specific, i.e. is the strongest for stimuli that activate a large number of visual cortical neurons. PMID- 1889001 TI - Metabolic effects of kynurenate during reversible forebrain ischemia studied by in vivo 31P-nuclear magnetic resonance spectroscopy. AB - The metabolic effects of kynurenate, an endogenous excitatory amino acid antagonist, were studied by in vivo 31P-NMR spectroscopy before, during and after reversible forebrain ischemia in the rat. Kynurenate had no effect on cerebral metabolism before ischemia. During a 30-min ischemia, kynurenate protected against the decrease in phosphocreatine (up to -55 +/- 3% vs -73 +/- 3% in the reference group) and the increase in inorganic phosphate (up to +479 +/- 39% vs +805 +/- 66%), whereas there was no statistical difference in the decrease in intracellular pH (up to 6.37 +/- 0.05 vs 6.30 +/- 0.03) and ATP (up to -60 +/- 3% vs -60 +/- 7%). The recovery of PCr, Pi, and pHi to control levels during recirculation was faster in the treated group than in the reference group, whereas the time course of ATP recovery was similar in both groups. We conclude that kynurenate protects against neuronal loss, as previously reported, by mechanisms other than metabolic protection. PMID- 1889003 TI - Evidence for a frontocortical-septal glutamatergic pathway and compensatory changes in septal glutamate uptake after cortical and fornix lesions in the rat. AB - To determine the source of glutamatergic input to the septum and to the nucleus accumbens septi, glutamate uptake was assessed after transections of the frontal cortex and/or fornix. Uptake in the septum and accumbens was reduced by 25 and 30% respectively, 6 days after bilateral frontal cortex transections. Both indices returned to control levels 30 days postoperatively. In contrast, while unilateral fornix transection did not affect uptake in the accumbens at either day 6 or 30, uptake in the septum was significantly reduced (25-35%) at both times. When a unilateral transection of the fornix was performed in rats with a pre-existing bilateral ablation of the frontal cortex, a further reduction in uptake was observed in the septum (50-60% at both 6 and 30 days after the fornix transection). The data implicate glutamate as a neurotransmitter in frontocortico septal projections and suggest that the contribution of the hippocampo-septal system to total glutamate uptake in the septum is increased following ablation of the frontocortico-septal system. PMID- 1889002 TI - Endoproteolytic conversion of beta-endorphin-1-31 to beta-endorphin-1-27 potentiates its central cardioregulatory activity. AB - Brain neurons that express the pro-opiomelanocortin gene secrete multiple forms of beta-endorphin (beta E) which subserve diverse bioregulatory processes. beta E 1-31, for example, is a potent analgetic but beta E-1-27 acts as an opioid antagonist and beta E-1-26, as well as the N-acetyl derivatives of all 3 peptides, lack opioid receptor activity. The present study examines the effects of beta-endorphin processing on its central cardioregulatory potency. Consistent with previous reports, intracisternal beta E-1-31 (1.5 nmol) injection lowered mean arterial pressure (MAP); MAP was reduced by 29.7 +/- 3.9 mm Hg at 60 min and returned toward baseline by 120 min. Unexpectedly, beta E-1-27 displayed a 10 fold greater hypotensive potency than beta E-1-31. At 0.15 nmol, it produced a response equivalent to 1.5 nmol beta E-1-31 while 1.5 nmol beta E-1-27 sustained a maximal reduction in MAP (49.2 +/- 3.9 mm Hg) throughout the 120-min test period. In contrast, beta E-1-26 and N-acetyl-beta E-1-26, -1-27 and -1-31 were inactive at 1.5 nmol. Bradycardia accompanied the depressor response to the higher beta E-1-27 dose but not to beta E-1-31. Naloxone pretreatment completely blocked the depressor effects of both beta E-1-31 and beta E-1-27, and reversed the bradycardia produced by beta E-1-27, suggesting that both peptides act through opioid receptors. beta E-1-27 also stimulated catecholamine release from the perfused adrenal gland but beta E-1-31 was inactive. These findings emphasize the importance of regionally selected post-translational processing in defining the functional specificity of beta E peptides. PMID- 1889004 TI - Area-specific hormonal regulation of brain aromatase. AB - In vitro experiments were conducted to compare the steroid regulation of aromatase in preoptic and posterior hypothalamic areas. Kinetic analysis of aromatase activity in the preoptic area (POA) and posterior hypothalamus (AHP) of castrated and intact doves indicate that both areas have a similar, high substrate affinity (apparent Km less than 15 nM), but castration decreases the Vmax to a greater extent in POA than AHP. This differential effect was confirmed using a single substrate (10 nM) concentration representing the Km of the enzyme. Comparison of the effects of non-aromatisable androgens, methyltrienolone (R1881) and 5 alpha-dihydrotestosterone (DHT), on aromatase activity in 20-day castrates showed that neither R1881 nor DHT induced aromatase activity in POA. This was confirmed in 40-day castrates which also showed a reduced inductive effect of testosterone (T) on the brain enzyme activity. R1881 specifically increased aromatase activity in AHP, but DHT did not affect either area. The non aromatisable androgens influenced androgen-dependent vocal behaviour to the same extent. Oestradiol (E2) increased aromatase activity in both POA and AHP. We conclude that non-aromatisable androgens affect hypothalamic, but not preoptic oestrogen formation. Aromatase activity in the male preoptic area associated with behaviour is specifically sensitive to the aromatisable androgen, T and E2. The results suggest that hormonal regulation of the aromatase differs locally within androgen target areas of the brain. PMID- 1889005 TI - Biochemical changes in isolated hepatocytes exposed to tert-butyl hydroperoxide. Implications for its cytotoxicity. AB - When isolated hepatocytes were exposed to tert-butyl hydroperoxide (tBOOH) they lost their cellular membrane integrity. Decreased levels of GSH, increased phosphorylase a activity (an indirect index of the amount of free cytosolic Ca2+), and increase in the formation of malondialdehyde (MDA)-like products (an index of lipid peroxidation) preceded the release into the culture medium of the cytosolic enzyme lactate dehydrogenase (LDH), indicating that this later process was the consequence of the former intracellular events. While ATP levels were not modified during the incubation of cells with increasing concentrations of tBOOH, protein synthesis was decreased in a concentration-dependent manner. The glycogen content decreased at the same time as the increase in LDH leakage. The addition of promethazine (PMZ) an antioxidant molecule, prevented the lipid peroxidation, but did not protect cells against the oxidative effects of tBOOH, including loss of membrane integrity. Nevertheless, the addition of GSH to cell suspensions incubated with tBOOH, decreased the formation of MDA-like products, restored the protein synthesis rate, prevented partially the activation of phosphorylase a and preserved cell viability. On the basis of these results, we postulate that both GSH depletion and modification in phosphorylase a activity (Ca2+ levels) were the most relevant intracellular events to explain the cytotoxicity of tBOOH. PMID- 1889007 TI - "Except for all others ...". PMID- 1889006 TI - Structure/activity investigations in eight arylalkyltriazenes comparison of chemical stability, mode of decomposition, and SCE induction in Chinese hamster V79-E cells. AB - A series of seven 1-aryl-3.3-dialkyltriazenes, including 1-phenyl-3.3 dimethyltriazene (DMPT), 1-phenyl-3.3-di-(trideuteromethyl)-triazene (DMPT-ds), 1 p-methylphenyl-3.3-dimethyltriazene (DMpMPT), 1-p-nitrophenyl-3.3 dimethyltriazene (DMpNPT), 1-phenyl-3.3-diethyltriazene (DEPT), 1-phenyl-3.3-di-n propyltriazene (DnPrPT) and 1-phenyl-3.3-diisopropyltriazene (DiPrPT) and 1.3 diphenyl-3-methyltriazene (DPMT), was synthesized and characterized by UV/VIS, IR and 1H-NMR spectroscopy. Chemical half-life was determined in phosphate buffer at 37 degrees using UV/VIS spectroscopy. With the exception of DMpNPT, which was stable, the triazenes underwent pH-dependent hydrolytic decomposition (acid catalysis). By means of UV/VIS spectra, TLC and HPLC, phenol, aniline and secondary azocoupling products were identified after complete hydrolytic cleavage of the parent compounds. Pathways of spontaneous hydrolysis are proposed and discussed. Genotoxic activity of the triazenes was assayed by measurement of sister chromatid exchanges (SCE) in V79-E cells without and with rat liver S9 mix as an exogenous metabolizing system. In the direct SCE assay (without S9 mix), all triazenes except DMpNPT exerted a toxic action (cell cycle delay) in a narrow concentration range between no effect and overt cytotoxicity. This non-specific toxicity depended on the pH of the incubation system and was inversely proportional to chemical half-life. The toxicity of these agents is most likely due to the arenediazonium cation which is a relatively stable intermediate. In a sublethal concentration range most triazeness induced significant increases of SCE rates. These are interpreted as an indirect consequence of cytotoxicity. Upon metabolic activation, the compounds were genotoxic in a dose-dependent fashion. Their SCE-inducing capacity depended on the nature of the alkylating species generated, i.e., the alkyldiazonium cation, and on chemical stability. Surprisingly, no deuterium isotope effect was observed in DMPT-d6. The order of genotoxic activity among the aryldialkyltriazenes was DMpNPT much greater than DMPT = DMPT-ds greater than DMpMPT much greater than DEPT greater than DnPrPT greater than or equal to DiPrPT. DPMT was a marginal SCE inducer but very toxic upon metabolic activation. As monooxygenation of DPMT, like spontaneous hydrolysis, should generate a phenyldiazonium cation, the results suggest that arylation of DNA causes a very low SCE induction, if any. PMID- 1889009 TI - Giving science a bad name. PMID- 1889008 TI - Consulting with specialists. PMID- 1889010 TI - Honing your referral skills. PMID- 1889011 TI - The self-sanitizing partial. PMID- 1889012 TI - Practice management & success. Ready-aim-fire. PMID- 1889013 TI - Dr. Gerald Niznick--a Canadian who made a difference. PMID- 1889014 TI - Complex impressions simplified with copper bands and warmed rubber base. PMID- 1889015 TI - The maintenance of osseointegrated implants. PMID- 1889016 TI - Peel bond strengths of five impression material tray adhesives. AB - The peel bond strengths of five impression materials and their tray adhesives to a perforated and non-perforated test surface were measured and the results were compared using a one-way ANOVA and Student Newman Keuls Multiple Range Test at p less than or equal to .05 level of significance. The auto-mix addition reaction silicone material Extrude produced the greatest peel bond strengths on both the non-perforated test surface (10.88 kg/cm2), and on the perforated test surface (15.88 kg/cm2). These bond strengths were greater than those obtained from the polysulphide and polyether materials used in the study. Using the perforated test surface significantly increased the peel bond strength for all the materials tested. It was concluded that in order to achieve the maximum adhesive bond, impression trays should be perforated. The greatest peel bond strengths were obtained using Extrude medium-body impression material. PMID- 1889017 TI - [Adolescents' fear of dental treatment: development and evaluation of a cognitive inventory]. AB - Morin et al.'s Inventaire cognitif de la peur des traitements dentaires pour adolescent(e)s [Adolescents' Fear of Dental Treatment Cognitive Inventory] was administered to 343 subjects. Factor analysis revealed a single general factor that accounted for 33.5 per cent of the total variance. A reliability test revealed an alpha coefficient of 0.91, which was quite acceptable. A measure of test-retest reliability over a four-week period (N = 181) indicated that the scale was stable over time (r = 0.85). Standard error of measurement was found to be 4.63. Normative data are provided along with a description of the final version of the scale. PMID- 1889018 TI - Skin exposure and thyroid dose distribution using niobium filtration. AB - A thermoluminescent dosimetry system was utilized to investigate how much the radiation dose is reduced through the addition of a niobium-based accessory filter to an X-ray unit's conventional aluminum filter. A two-bitewing series was exposed in a tissue-equivalent human phantom. The skin exposures from an X-ray beam with the added niobium filter and a beam with the aluminum filter alone were measured and compared. Thyroid dose distribution was also measured and similarly compared. Utilization of the niobium filter resulted in a significant reduction in skin exposure (p less than 0.001) of 14.8 per cent. Thyroid dose was not lessened by using the niobium filter, however. In fact, in one region of the thyroid it increased significantly. PMID- 1889019 TI - Orbital lesions with granulomatous inflammation. AB - Orbital lesions characterized by granulomatous inflammation are a heterogeneous group of diseases of various causes with a common histopathological substrate involving aggregates of epithelioid cells. Forty-one patients (27 females and 14 males) with biopsy-proven granulomatous inflammation were seen at an orbital clinic between 1978 and 1989. The mean age at presentation was 40.2 (extremes 6 and 77) years. Two main clinical presentations were noted: painless, subacute or chronic mass effect, and tender, subacute inflammatory process. Six patients had secondary features that were infiltrative in character. The lesions were primarily located in the anterior superior orbit. In nearly half the patients the granulomatous reaction was confined to the orbit (predominantly ruptured dermoid and localized orbital sarcoid), and the remainder had either regional involvement (Wegener's granulomatosis or fibro-osseous process) or systemic involvement (sarcoidosis). PMID- 1889020 TI - Effect of vitrectomy on the ocular distribution of gentamicin in the rabbit. AB - To determine whether vitrectomy affects the ocular distribution of intravitreally injected gentamicin sulfate, 25 pigmented rabbits received an intravitreal injection of gentamicin (control group), and 25 other pigmented rabbits underwent pars plana vitrectomy followed by an intravitreal injection of gentamicin (experimental group). The animals were killed in groups of five 1, 3, 6, 12 and 24 hours after the injection. The mean retinal gentamicin levels 1 and 3 hours after the injection were significantly higher in the experimental group than in the control group (p less than 0.01). The mean gentamicin level in the aqueous humour was significantly lower in the experimental group than in the control group 1 hour (p less than 0.01), 6 hours (p less than 0.01) and 24 hours (p less than 0.001) after the injection. The mean corneal gentamicin level 24 hours after the injection was significantly lower in the experimental group than in the control group (p less than 0.05). There was no significant difference in mean choroidal gentamicin level between the two groups. We conclude that vitrectomy significantly affects the ocular distribution of gentamicin in the rabbit. PMID- 1889021 TI - Ocular pharmacokinetics of subconjunctivally administered cyclosporine in the rabbit. AB - The authors assessed the ocular toxicity and pharmacokinetics of subconjunctivally and intravenously administered cyclosporine in New Zealand white rabbits. Fifteen rabbits received a subconjunctival injection of 5 (five animals), 10 (five animals) or 25 (five animals) mg of cyclosporine in 0.1 mL (intravenous solution of Sandimmune [50 mg/mL]); 5 mg was found to be the maximum tolerable dose. This dose was given as a bolus to 36 other rabbits either subconjunctivally (18 animals) or intravenously (18 animals). In both groups the cyclosporine concentrations in the ocular compartments, blood and urine were measured by means of high-pressure liquid chromatography at 0.5, 1, 2, 4, 8 and 12 hours, three animals being assessed at each interval. Subconjunctival administration resulted in peak cyclosporine concentrations of 718 ng/mL in the aqueous humour and 1078 ng/mL in the vitreous humour, compared with no detectable levels in the aqueous humour and a peak concentration of 292 ng/mL in the vitreous following intravenous administration. The peak blood cyclosporine levels were 10 times lower after subconjunctival injection than after intravenous injection. The results indicate that subconjunctival administration is superior to intravenous administration in enhancing the ocular absorption of cyclosporine while minimizing systemic exposure in the rabbit. PMID- 1889022 TI - Corneal transplantation in infants, children and young adults: experience of the Toronto Hospital for Sick Children, 1979-88. AB - Between 1979 and 1988, 85 penetrating keratoplasty procedures were performed in 54 patients aged 1 month to 18.2 years at the Hospital for Sick Children, Toronto. The minimum length of follow-up was 3 months. A clear transplant was obtained in 27 eyes: 7 of 16 eyes with Peter's anomaly, 0 of 8 eyes with congenital glaucoma, 2 of 5 eyes with herpes simplex keratitis, 6 of 8 eyes with corneal dystrophy and 12 of 17 eyes with traumatic corneal scars. The most recent visual acuity was best in the trauma and dystrophy groups and worst in the congenital glaucoma group. Visual acuity results were better in older children and were fair in younger children and those with postoperative complications. Although penetrating keratoplasty is more difficult in children than in adults, it has a reasonable chance of success. However, the poor outcome in the congenital glaucoma group indicates that the procedure is not warranted in such patients. PMID- 1889023 TI - Cardiovascular effects of levobunolol eyedrops in healthy subjects. AB - The cardiovascular side effects of the abrupt cessation of treatment with 0.5% levobunolol hydrochloride eyedrops in 10 healthy subjects (5 women and 5 men) aged 18 to 30 years were investigated in a double-blind randomized crossover study. The subjects received either levobunolol eyedrops or placebo drops for 7 days, then, after a 14-day washout period, they received the alternative drops for 7 days. The heart rate and blood pressure at rest, the maximal heart rate and blood pressure on treadmill exercise stress testing and duration of exercise were recorded before treatment began, at the end of treatment and 14 days after withdrawal of the drops. The mean resting heart rate was significantly lower during treatment with levobunolol than with placebo (p less than 0.05). The mean exercise duration was significantly longer during treatment with levobunolol (p less than 0.05); to our knowledge, we are the first to report this finding. There were no significant differences in mean arterial pressure, double product (product of heart rate and systolic blood pressure) or maximal heart rate between the groups at any measurement. PMID- 1889024 TI - Contact thermal burns of the cornea. AB - The records of 59 patients (66 eyes) with contact thermal burns of the cornea (unilateral in 52 cases and bilateral in 7) were reviewed to determine the causes, clinical presentation, management and complications of such injuries. Most of the injuries (90%) occurred at home. The commonest cause was splashing of boiling fluids (42% of cases), followed by contact with red-hot firecracker particles (18%) and lit match heads (17%). In 59 eyes (89%) the burn was limited to the corneal epithelium, in 5 (8%) the superficial stroma was also involved, and in 2 (3%) there was associated corneal perforation caused by mechanical impact of foreign bodies. Debridement of the coagulated epithelium with patching was the most successful treatment, healing 48 (73%) of the eyes. Postburn complications were rare, the most common being development of inferior symblepharon, in three eyes (4%). PMID- 1889025 TI - Results of surgery to modify the null-zone position in congenital nystagmus. AB - The author reports the long-term (average 11 years) results of surgery to correct the face turn or tilt adopted to use the null zone associated with nystagmus. Of the 18 patients 16 had a face turn (7 with fusion and no strabismus, and 9 without fusion and strabismus) and 2 had a head tilt. Surgery was done after the age of 7 years (average 11 years), the same amount of surgery being done on all four horizontal rectus muscles in patients without strabismus to turn the eyes in the same direction as the face turn. Ten-millimetre recession/resection surgery produced the best correction of the face turn and the most gaze restriction. In patients with straight eyes before surgery strabismus was not produced or fusion or stereopsis lost. In patients with strabismus, surgery was modified on the nonfixing eye to correct the strabismus in addition to the face turn. PMID- 1889026 TI - Management of suspected ocular laceration or rupture. AB - The records of 95 consecutive patients with suspected ocular laceration or rupture managed by a single surgeon were reviewed. A total of 86 patients were found to have a laceration or rupture, of whom 79 were followed up, for an average of 6.4 months. In 32 eyes (40%) the final visual acuity was 20/40 or better, and in another 32 the final acuity was less than 5/200. Eyes with lacerations had a better visual outcome than those with rupture due to blunt trauma. Of the 26 eyes operated on for suspected blunt rupture 6 (23%) were found not to have a rupture. Ruptured eyes were more likely than nonruptured eyes to have abnormal anterior chamber depth, vision less than hand motion and hyphema. PMID- 1889027 TI - Incontinentia pigmenti (Bloch-Sulzberger syndrome): a case report and review of the ocular pathological features. AB - Incontinentia pigmenti (IP) (Bloch-Sulzberger syndrome) is an X-linked dominant condition usually fatal in males. Shortly after birth affected girls present with a rash followed by pigmentary changes. Abnormalities of the central nervous system and dentition are often present, and ophthalmic problems develop in approximately one-third of patients. The authors present the pathological findings in the skin and eye in a young woman who required enucleation as a result of long-standing retinal detachment and closed-angle glaucoma. A review of published ocular pathology reports indicates that retinal detachment and a fibrovascular retrolental membrane are the commonest intraocular abnormalities in IP. Changes in the retinal pigment epithelium are also prominent, although whether these are primary or secondary remains to be established. PMID- 1889028 TI - Ophthalmologists treated unfairly in fee increases and income-disparity adjustments. PMID- 1889029 TI - The Canadian Council on Animal Care--its guidelines and policy directives: the veterinarian's responsibility. PMID- 1889030 TI - The effect of porcine follicular fluid on the interaction of boar spermatozoa with zona-free hamster ova. AB - Boar spermatozoa were cocultured with zona-free hamster ova (eggs) to assess the effects of preovulatory porcine follicular fluid (pFF) in the capacitation medium or gamete coculture (fertilization) medium (pFF; 0, 10 or 40% v/v) on subsequent sperm-egg interaction. Increasing pFF concentrations in the capacitation medium resulted in a progressive decrease in the average numbers of sperm attaching to or penetrating each ovum. When pFF was included in the fertilization medium, but not in the capacitation medium, the average numbers of sperm attaching to or penetrating each ovum and the percentage of ova with sperm attached decreased markedly with increasing pFF concentrations. The percentage of ova with greater than five sperm attached decreased from 84% to 13% and 0% with 0%, 10% and 40% pFF, respectively. Sperm attachment was completely inhibited in approximately 50% of the ova cocultured in 40% pFF. The percentage of ova penetrated by greater than five sperm decreased from 82% to 21% and 7% with 0%, 10% and 40% pFF, respectively. Preincubation of ova in 40% pFF prior to coculture with sperm also resulted in a reduction in sperm attachment and penetration. These results suggest that pFF contains substance(s) that alter the ability of boar spermatozoa to interact with the hamster ovum plasma membrane in vitro. PMID- 1889031 TI - The effect of lipopolysaccharide on bovine mammary macrophage function. AB - The effect of Escherichia coli lipopolysaccharide (LPS) on the expression of major histocompatibility complex (MHC) class II molecules by bovine mammary macrophages was examined. The ability of LPS-treated mammary macrophages to support antigen-specific T-cell proliferation, as a measure of their antigen presentation ability, was also evaluated. For this purpose, control and LPS treated macrophages were pulsed with heat-killed Staphylococcus aureus and then cultured with S. aureus-sensitized T-cells. Our data show that LPS had no significant effect on the expression of MHC class II molecules on the surface of mammary macrophages. Furthermore, LPS-induced macrophages were no more active in supporting T-cell proliferation on a per cell basis than unstimulated macrophages. The lack of macrophage response to LPS with respect to expression of MHC class II molecules and the antigen presentation ability is another example of the hyporesponsive nature of macrophages isolated from the bovine mammary gland. PMID- 1889032 TI - Atrophic rhinitis caused by Pasteurella multocida type D: morphometric analysis. AB - In order to study the distribution and the extent of atrophy caused by Pasteurella multocida in the nasal conchae, experimental piglets were injected intramuscularly at seven days of age with either two or four 50% mouse lethal doses per kg body weight of P. multocida type D dermonecrotoxin. Experimental and control piglets were killed four, six and ten days postinjection. Serial transverse paraffin embedded sections of the noses were cut throughout the entire length of the nasal conchae. The area of the nasal ventral conchae was measured and the morphometric index of the nasal cavity was calculated. It was observed that P. multocida type D dermonecrotoxin induced severe atrophy of the nasal ventral conchae. This atrophy was present along the entire conchae. However, it was most severe at the level of the first and second premolar teeth. PMID- 1889033 TI - Distribution of atrophy in the nasal ventral conchae of piglets infected experimentally with Bordetella bronchiseptica. AB - The distribution and extent of atrophy caused by Bordetella bronchiseptica in the nasal ventral conchae were investigated by intranasally infecting piglets at day 4 of life. Experimental and control piglets were killed at one, two, three, four, five and six weeks of age. Serial transverse 80 microns thick nondecalcified sections were cut throughout the entire length of the nasal ventral conchae, and microradiographed. It was observed that the distribution and extent of atrophy was not uniform along the ventral conchae. The articular and transverse laminae as well as the connecting zone were not atrophied, except at their rostral extremity. The entire dorsal scroll was atrophied. This atrophy was moderate, except at the rostral and caudal extremities of the dorsal scroll, where its size was less than half that of the controls. The ventral scroll was less atrophied than the dorsal scroll, although a marked atrophy was present at its rostral extremity. From these observations, it is suggested that two transverse sections should be made through the nose of pigs in order to establish a diagnosis of atrophic rhinitis at slaughter: one section at the level of the first-second premolar tooth and one more rostral section, at the level of the canine tooth. PMID- 1889034 TI - Naturally acquired Pasteurella multocida infection in rabbits: clinicopathological aspects. AB - A cohort of 41 New Zealand White rabbits, 35 to 60 days old, from twelve litters were followed for twelve weeks for development of pasteurellosis. Eleven of 19 rabbits in five litters acquired Pasteurella multocida infection. The incubation period was difficult to determine as P. multocida infection was detected both before and after the onset of rhinitis. The response of rabbits to infection varied from subclinical infection to death from systemic pasteurellosis. Atrophy of the maxilloturbinates of the nares was detected in rabbits with chronic rhinitis associated with P. multocida infection. PMID- 1889036 TI - An epidemiological study of paratuberculosis in dairy cattle in Ontario: study design and prevalence estimates. AB - An observational study involving 304 dairy herds and three abattoirs was conducted between 1986 and 1989 to investigate the epidemiology of paratuberculosis in dairy cattle in Ontario. The objectives of this paper were to describe the method of data collection for the study, to present descriptive production statistics and to present estimates of the prevalence of paratuberculosis among dairy cattle in Ontario. Mycobacterium paratuberculosis was isolated from the distal ileum and/or the ileocecal lymph node of 5.5% of 400 cull cows. Based on a lipoarabinomannan antigen enzyme-linked immunosorbent assay (LAM-ELISA) on sera, the predicted true prevalence of paratuberculosis among 14,923 dairy cattle from 304 herds, was 6.1%. Nineteen percent of 2,943 fecal cultures were uninterpretable because of overgrowth with contaminating bacteria or fungi. It was concluded that the true prevalence of paratuberculosis among dairy cattle in Ontario was no greater, and may be less than the true prevalence among dairy cattle from various regions of the United States. However, at a practical level, for the purposes of trade policy, the present study suggests that the functional prevalence is very similar in the two countries. PMID- 1889035 TI - Detection and characterization of leptospiral antigens using a biotin/avidin double-antibody sandwich enzyme-linked immunosorbent assay and immunoblot. AB - A biotin/avidin double-antibody sandwich enzyme-linked immunosorbent assay (ELISA) for the detection of antigens of Leptospira interrogans serovars in experimentally inoculated bovine urine samples was evaluated. Immunoglobulin G (IgG) from rabbits immunized with L. interrogans serovar hardjo type hardjobovis sonicated, whole cell, and formalinized-heated antigen preparations were purified by a protein A-superose column coupled to fast protein liquid chromatography, and evaluated for species specificity in the ELISA. The ELISA using each specific IgG detected as few as 10(4) leptospires of the homologous serovar hardjo diluted in phosphate-buffered saline solution with Tween 20 (PBSS-Tween 20). On immunoblot analysis of proteinase-K-digested whole cell leptospiral preparations, each IgG revealed the presence of bands specific to serovar hardjo, suggesting the presence of serovar-specific epitopes on the lipopolysaccharide molecules. The minimum number of cells of heterologous serovars pomona, grippotyphosa, bratislava, icterohaemorrhagiae and copenhageni detected by each ELISA was greater, ranging from 10(6) to 10(7). The common antigenic determinants observed on immunoblot analysis were different for each specific IgG, except for a major cross-reacting, possibly flagellar, protein doublet at approximately 36-36.5 kDa. Leptospires were equally well detected by the ELISA in both bovine urine and PBSS Tween 20. PMID- 1889037 TI - Serological diagnosis of cysticercosis by an enzyme-linked immunosorbent assay in experimentally infected cattle. AB - Taenia saginata infections were established in four groups of calves by administering doses of 10, 10(2), 10(3) and 10(4) infective eggs respectively by gavage. A fifth group remained as uninfected controls. Sera were collected from all calves over a period of 210 days. The sera were examined by an enzyme-linked immunosorbent assay (ELISA) with a fraction of larval Taenia hydatigena cyst fluid as antigen for the presence of anti-T. saginata IgG antibodies. At slaughter, the tongue, masseter, diaphragm and cardiac muscles and liver were examined for cysticerci. The higher dose rates of T. saginata eggs were reflected in higher numbers of cysticerci found in the calves at necropsy. There was also a correlation between higher levels of antibodies produced as measured by the ELISA and the numbers of eggs given. Sero-conversion was first detected about 25 days postinfection in heavy infections and later in the lighter infections. Maximal levels of antibody occurred between 40 and 60 days postinfection, followed by a gradual decrease in levels of antibody. A secondary increase in antibody occurred between 160 and 200 days postinfection which might have been due to release of antigen after death of the cysticerci. The low level of circulating antibodies in light infections may result in false positive or false negative diagnoses depending upon the selection of the cut-off point. PMID- 1889038 TI - Epidemiological approach to the association between economic efficiency and productivity on swine farms in Prince Edward Island. AB - Regression analysis was used to determine the ability of a number of biological parameters to predict economic efficiency. Detailed feed, financial, and production records were maintained by a random sample of eighteen Prince Edward Island (PEI) swine producers (each producing over 1000 market hogs per year). Relative economic efficiency of the operations was measured using return to management and labor (RML). Of the routinely monitored biological parameters, RML on PEI farrow-finish operations was best predicted (R2 = 64.8%) by: marketed per square meter per year (p = 0.008) and marketed per sow per year (p = 0.096). Regression of fixed costs revealed that biological parameters had limited ability to predict fixed costs per hog on farrow-finish operations (R2 = 30.7%). The only parameter contributing to the prediction of the fixed cost component of RML was feeder hog density (p = 0.077). The variable cost component of RML on farrow finish operations was predicted (R2 = 94.3%) by feed cost per kg gain (p = 0.000), and marketed per sow per year (p = 0.044). The routinely recorded biological parameters on feeder farms had only limited ability to predict RML in this study (R2 = 43.7%). The only parameter of any importance was marketed per square meter per year (p = 0.106). Prediction of the fixed cost component of RML on feeder farms (R2 = 67.4%) was best realized by measuring feeder hog density (p = 0.045). The variable cost component of RML on feeder farms was reasonably well predicted (R2 = 74.7%) by feed cost per kg gain (p = 0.012). Although this parameter is difficult to monitor from records currently maintained on most farms, it points out the need to monitor feed consumption on swine farms. PMID- 1889039 TI - Histamine inhalation challenge in normal horses and in horses with small airway disease. AB - A histamine inhalation challenge (HIC) procedure was developed to assess hyperreactive states in horses. Following clinical evaluation, percutaneous lung biopsies were performed on nine light breed mares aged 6 to 15 years. Five horses, with normal small airways, were classified as group A and four subjects with small airway disease (SAD) lesions formed group B. Pulmonary mechanics parameters were monitored following an aerosol of 0.9% saline and every 5 min for up to 30 min after HIC with 0.5% w/v of histamine diphosphate, administered through a face mask for 2.5 min. Tidal volume (VT) and airflow (V) values were obtained with a pneumotachograph. Transpulmonary pressure (delta Ppl) was measured by the esophageal balloon catheter method. Dynamic compliance (Cdyn), total pulmonary resistance (RL), end expiratory work of breathing (EEW) and respiratory rate (f) were calculated by a pulmonary mechanics computer. Group A horses had increases in RL, and decreases in Cdyn whereas horses in group B were hyperreactive and showed greater changes in EEW, Cdyn, and delta Ppl but with a relatively lower variation of RL. One horse in clinical remission from SAD, but with a high biopsy score (group B), and one clinically normal horse belonging to group A showed marked hyperreactivity as shown by increases in EEW, maximum change in delta Ppl and RL and decreases in Cdyn. These results suggest that the HIC described can be used as a method to investigate airway hyperreactivity and SAD in horses. PMID- 1889040 TI - Effects of season and stage of gestation on luteinizing hormone release in gilts. AB - This study was designed to examine the effects of two seasons and stage of gestation on luteinizing hormone (LH) release in the gilt. Eleven Yorkshire Landrace crossbred gilts were each fitted with an indwelling vena caval cannula. Blood samples were collected at 6 h intervals for six days during early (day 39 to 44) or mid-gestation (day 69 to 74). Serum progesterone, estradiol-17 beta and LH concentrations were determined in samples collected at 6 h intervals. Early and mid-gestation occurred during August and September in group 1 (n = 6) and during January and February in group 2 gilts (n = 5). To characterize pulsatile LH release, samples were collected at 15 min intervals for 8 h on day 40, 43, 70 and 73 of gestation. Following each 8 h sampling period, gilts were treated intravenously with 0.5 micrograms gonadotropin-releasing hormone (GnRH)/kg body weight and blood collected at 10 min intervals for 3 h. Progesterone concentrations decreased (p less than 0.01) from 22.1 +/- 0.4 ng/mL during early gestation to 18.2 +/- 0.4 ng/mL during mid-gestation. Estradiol-17 beta concentrations increased (p less than 0.01) from early to mid-gestation (13.5 +/- 0.8 versus 28.4 +/- 0.7 pg/mL). Frequency of LH pulses and LH pulse amplitude were higher (p less than 0.05) in pregnant gilts during January and February compared to August and September.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1889041 TI - Adherence of Streptococcus suis capsular type 2 to porcine lung sections. AB - The present study was undertaken to evaluate the ability of 33 Streptococcus suis capsular type 2 isolates to adhere to frozen sections of porcine lung. Twenty isolates originated from diseased pigs and 13 from the nasal cavities of clinically healthy pigs. All isolates from diseased animals adhered to lung sections; isolates from pneumonia adhered, in general, in greater numbers than isolates from meningitis. Only four isolates from clinically healthy animals showed a weak adherence to lung sections. Hydrophobic surface properties were also evaluated. All isolates tested appeared to possess a hydrophilic cell surface. The thickness of the capsular material correlated well with the degree of adherence. However, when the adherence capacity of a noncapsulated mutant was compared with that of the parent strain, it was found that the mutant strain had at least the same adherence capacity as the capsulated parent strain. The data suggest that S. suis capsular type 2 isolates involved in pathological conditions can adhere to porcine lung tissue. The adherence activity does not seem to involve hydrophobic interactions. The amount of capsular material seems to influence the adherence activity, but is probably not the only mechanism involved. PMID- 1889042 TI - Human infections associated with Bordetella bronchiseptica. AB - This study examines the potential of Bordetella bronchiseptica to act as a human pathogen. After encountering two patients from whom B. bronchiseptica was isolated, we searched the literature and found 23 reports in which a human infection was reported in association with B. bronchiseptica. As a basis for evaluating these cases, we summarize the literature about the current microbiological status of B. bronchiseptica, the pathology and pathogenic mechanisms associated with the microorganism, and the likelihood of it acting as a commensal or colonizer. From this review we conclude that B. bronchiseptica has been rarely isolated from humans despite their considerable exposure to animal sources. Evidence suggests that B. bronchiseptica may be rarely encountered as a commensal or colonizer of the respiratory tract of humans and rarely in association with infection. When found as a probable pathogen, most infections have been respiratory tract in origin and have occurred in severely compromised hosts. PMID- 1889043 TI - Diversity and origin of rheumatologic autoantibodies. AB - A hallmark of sera from patients with systemic rheumatic diseases is the presence of circulating autoantibodies directed against nuclear antigens. The identification of the antigens binding to these antibodies has provided the cell biologist and the immunologist with important tools to study cell structure, cell function, and the processes underlying the immune response. Through the elucidation of autoantibody specificities, the clinician has been provided with a better appreciation of the diagnostic and prognostic significance of autoantibodies. Many autoantigens, including those directed against components in the nuclear matrix, chromosomes, Golgi apparatus, and other intracellular antigens, are not yet characterized nor is their clinical significance established. The mechanisms leading to the breakdown of tolerance and the appearance of autoantibodies are not fully understood. Molecular mimicry at an interspecies or an intracellular level may be involved in altering immune tolerance. On the other hand, studies of epitopes on human autoantigens has provided compelling evidence that most autoantibody responses seen in systemic rheumatic diseases are driven by endogenous antigen. PMID- 1889044 TI - The tribe Ehrlichieae and ehrlichial diseases. AB - The tribe Ehrlichieae consists of gram-negative minute cocci that are obligate intracellular parasites classified in the family Rickettsiaceae. Although ehrlichial organisms have been observed in leukocytes for many years, only a few species have been cultured in quantities sufficient for biochemical and molecular analyses. Recents studies on 16S-rRNA sequence analysis and energy metabolism showed that the genus Ehrlichia is closely related to the genus Rickettsia. There is, however, no antigenic cross-reactivity between these genera. Ehrlichial organisms cause a disease called "ehrlichiosis," a noncontagious infectious disease known to be transmitted by a tick in several cases and by a fluke in one case. Ehrlichia spp. infect dogs, ruminants, horses, and humans. Recently, two new ehrlichial diseases, Potomac horse fever and human ehrlichiosis, were discovered in the United States. The etiologic agent of Potomac horse fever, Ehrlichia risticii, is closely related to the known human pathogen Ehrlichia sennetsu. The etiologic agent of human ehrlichiosis is related to Ehrlichia canis, a canine pathogen. In contrast to the genus Rickettsia, members of the tribe Ehrlichieae reside primarily in the cytoplasmic vacuoles of monocytes or granulocytes and cause hematologic abnormalities, lymphadenopathy, and other pathologic changes in the host. However, the actual mechanisms whereby Ehrlichia spp. infect leukocytes, multiply in them, and produce various forms of systemic disease have not been defined. Depending on the ehrlichial species involved, serologic or direct microscopic observation of stained blood smears is currently used to diagnose ehrlichial disease. PMID- 1889045 TI - Factors promoting acute and chronic diseases caused by yersiniae. AB - The experimental system constructed with the medically significant yersiniae provides a powerful basic model for comparative study of factors required for expression of acute versus chronic disease. The system exploits the close genetic similarity between Yersinia pestis, the etiological agent of bubonic plague, and enteropathogenic Yersinia pseudotuberculosis and Yersinia enterocolitica. Y. pestis possesses three plasmids, of which one, shared by the enteropathogenic species, mediates a number of virulence factors that directly or indirectly promote survival within macrophages and immunosuppression. The two remaining plasmids are unique and encode functions that promote acute disease by enhancing bacterial dissemination in tissues and resistance to phagocytosis by neutrophils and monocytes. These properties are replaced in the enteropathogenic yersiniae by host cell invasins and an adhesin which promote chronic disease; the latter are cryptic in Y. pestis. Additional distinctions include specific mutational losses in Y. pestis which result in loss of fitness in natural environments plus gain of properties that facilitate transmission and infection via fleabite. PMID- 1889048 TI - Relation of left atrial size to pulmonary capillary wedge pressure in severe mitral regurgitation. AB - 4,071 consecutive cardiac catheterizations were reviewed retrospectively to obtain 56 cases of pure mitral regurgitation among whom chest X-ray, electrocardiography and echocardiography had been performed within 10 days of catheterization. Mitral regurgitation was mild to moderate (1-2+) in 7 of the 56 cases while 49 had more severe regurgitation (3-4+). Left atrial size as measured by echocardiography was found to be enlarged in all but 2 cases. A positive correlation between left atrial size and severity of mitral regurgitation, irrespective of the height of the pulmonary capillary wedge pressure V wave was demonstrated. There was no demonstrable, predictive relationship between left atrial size and pulmonary capillary wedge pressure or electrocardiographic or chest X-ray findings. We conclude that knowledge of left atrial size is predictive of the severity of mitral regurgitation; however, it is not possible to predict the pulmonary capillary wedge pressure or height of the V waves based on a knowledge of left atrial dilatation in patients with pure mitral regurgitation. PMID- 1889049 TI - Systemic and pulmonary flow in mitral stenosis: evidence for a bronchial vein shunt. AB - We measured pulmonary and systemic flows in 22 patients with mitral stenosis and in 7 controls. In patients with mitral stenosis, pulmonary flow index averaged 2.33 +/- 0.41 l/min/m2 and systemic flow index averaged 2.15 +/- 0.60 l/min/m2, p = 0.045. There was a strong correlation between the difference in pulmonary and systemic flow indexes and the difference in mean left and right atrial pressure (r = 0.749, p = 0.00008). After a successful dilatation in 17 patients, there was a significant drop in the difference between pulmonary and systemic flow indexes (0.26 +/- 0.41 vs. 0.07 +/- 0.37 l/min/m2, p = 0.048). We conclude that chronic elevation of left atrial pressure leads to a left to right shunt probably through bronchial veins. PMID- 1889050 TI - Importance of coronary collateral circulation for increased treadmill exercise capacity by nitrates in patients with stable effort angina pectoris. AB - The purpose of this study was to elucidate the mechanism that induces an improvement in exercise capacity by nitrates in patients with stable effort angina pectoris. The study population was composed of 19 patients: group A, 10 patients with chronic stable effort angina who had a well-developed coronary collateral circulation to the potentially ischemic region; group B, 9 patients with chronic stable effort angina who had no collateral circulation to the jeopardized myocardium. Treadmill exercise was performed according to the standard Bruce protocol with and without pretreatment with orally administered 10 mg isosorbide dinitrate. Percent increases (mean +/- SE) in exercise duration were not significantly different between groups A and B (25 +/- 6 vs. 14 +/- 6%). Percent increases in the maximal rate-pressure product tended to be greater in group A than in group B (27 +/- 6 vs. 10 +/- 6%). Percent increases in the rate pressure product at the onset of angina pectoris were significantly greater in group A than in group B (37 +/- 7 vs. 7 +/- 6%; p less than 0.01). Percent increases in the rate-pressure product at 0.1 mV S-T segment depression were also significantly greater in group A than in group B (26 +/- 6 vs. 1 +/- 5%; p less than 0.01). These results suggest that isosorbide dinitrate dilates epicardial collateral vessels with smooth muscle layers, but fails to dilate the coronary arteries with significant organic stenoses. PMID- 1889051 TI - Natural history of hypertrophic cardiomyopathy in the elderly. AB - To assess the natural history of hypertrophic cardiomyopathy (HC) in the elderly, we reviewed clinical, electrocardiographic and hemodynamic data from 21 patients over 60 years of age at diagnosis who were studied since 1970. Comparison with 95 younger patients (less than 60 years) showed that a greater proportion of older patients had exertional angina and atrioventricular conduction delay at time of diagnosis. During a mean follow-up of 9 +/- 6 years, mortality from cardiac causes was 33% (7 out of 21) in patients over 60 years of age and 23% (22 out of 95) in younger patients (NS). Univariate analysis showed that functional class and hemodynamic indices of right- and left-sided heart impairment were associated with a poor prognosis in the elderly. We conclude that: (1) presenting features and outcome of patients with HC over 60 years of age do not differ significantly from those of younger patients; (2) functional class and measurements of cardiac function are significant predictors of death in the elderly. PMID- 1889052 TI - Three echocardiographic methods in right ventricular function evaluation. AB - We employed two-dimensional echocardiography for the assessment of right ventricular (RV) volumes and/or function in a series of 44 patients. The results of three different echocardiographic approaches were compared with the data obtained from single-plane RV angiography following ultrasound within a 7-day interval. Only the echocardiographic area length method with two orthogonal imaging planes employed (apical 4-chamber and subcostal projections) yielded the beneficial results. The correlations between echocardiographic and angiographic RV volume estimates were rather high (end-diastolic volume: r = 0.83, end systolic volume: r = 0.82, stroke volume: r = 0.81) and satisfactory in ejection fraction (r = 0.75). Using the method mentioned, the differentiation of patients with an angiographic evidence of RV failure (echocardiographic ejection fraction less than 0.55) from those without it was possible with a sensitivity of 0.68 and a specificity of 0.82. Concerning the clinical impact of the presented study, we can recommend the technique in question as a screening procedure for the detection of changes in RV function exceeding 12% (95% confidence limits). PMID- 1889053 TI - Evaluation of aortic regurgitation by cardiac cine magnetic resonance imaging: planar analysis and comparison to Doppler echocardiography. AB - Cine magnetic resonance imaging (MRI) displays cardiac flow in cine loop fashion on multiple tomographic sections. Since laminar flow is easily distinguished from turbulent flow, cine MRI may be uniquely suited to the study of valvular regurgitation: the entire cardiac volume can be sampled and the regurgitant jet at the valve plane can be depicted. We therefore assessed aortic regurgitation (AR) by cine MRI in 35 patients and 11 normal volunteers and compared results to pulsed (n = 32) or color flow Doppler (n = 14). The extent of the flow disturbance was estimated for both cine MRI and Doppler by indexing the size of the maximal, single plane regurgitant jet area (JA) to the left ventricular (LV) area. Cine MRI JA/LV ratio compared well with pulsed (r = 0.81) and color flow (r = 0.88) Doppler; classification as mild (less than 20%), moderate (20-40%), and severe (greater than 40%) AR by both methods was identical in 43 of 46 cases with no differences of more than one grade. Overall sensitivity and specificity of cine MRI, compared to Doppler, were 94 and 95%, respectively. Cine MRI also depicted the regurgitant jet at the valve plane in 11 patients. Thus planar analysis of cine MRI images in patients with AR provides a semiquantitative assessment of the AR flow disturbance which is similar to Doppler but, in addition, can image the entire cardiac volume and the regurgitant jet at the valve plane. PMID- 1889046 TI - Cryptosporidiosis. AB - Before 1982, only eight case reports of human cryptosporidiosis and fewer than 30 papers on Cryptosporidium spp. appeared in the biomedical literature. At that time, cryptosporidiosis was thought to be an infrequent infection in animals and rarely an opportunistic infection in humans. The concept of Cryptosporidium spp. as pathogens has changed dramatically within the past 8 years because of improved diagnostic techniques, increased awareness within the biomedical community, and the development of basic research programs in numerous laboratories. Presently, greater than 1,000 publications including over 400 case reports in the biomedical literature address Cryptosporidium spp. and cryptosporidiosis. Cryptosporidium parvum is now thought to be one of the three most common enteropathogens causing diarrheal illness in humans worldwide, especially in developing countries. It is likely that cryptosporidiosis was previously included in the 25 to 35% of diarrheal illness with unknown etiology. Because of the severity and length of diarrheal illness and because no effective therapy has been identified, cryptosporidiosis is one of the most ominous infections associated with AIDS. The role of C. parvum as an enteropathogen is well established; documentation of its role as a cause of hepatobiliary and respiratory diseases is now appearing in the literature. Our present understanding of the natural history, epidemiology, biology, and immunology of Cryptosporidium spp. as well as the clinical features, pathogenicity, and treatment of cryptosporidiosis are reviewed here. PMID- 1889055 TI - A case of malignant lymphoma simulating acute myocardial infarction. AB - A patient with malignant lymphoma suddenly collapsed, and ST segment elevation with complete atrioventricular block was observed on his electrocardiogram during an episode resembling acute myocardial infarction. Cardiac cineangiography revealed posterobasal asynergy of the left ventricle with no significant obstruction in the coronary arterial tree. Autopsy revealed diffuse invasion of the myocardium by lymphoma cells. Left ventricular wall motion was preserved even in the area of massive invasion; there was no true necrosis. Myocardial biopsy may be indicated in patients in whom there is a discrepancy between coronary pathoanatomy and wall motion abnormalities. PMID- 1889054 TI - Lipid and lipoprotein abnormalities in South African Indian men with myocardial infarction. AB - The Indian (Asian) population in South Africa has a high rate of coronary artery disease. Fasting serum lipid and lipoprotein levels were measured in 620 consecutive male survivors of myocardial infarction and compared with those of 524 healthy male volunteer controls, and the presence of hypercholesterolaemia and hypertriglyceridaemia in the patient group was related to other non-lipid coronary risk factors. All survivors and controls were below age 61 years. Total cholesterol, triglyceride and low-density-lipoprotein cholesterol concentrations varied significantly with age both in patient and control groups, whereas high density-lipoprotein (HDL) cholesterol did not vary with age in either group. Using the 90th-percentile age-adjusted values of controls for total cholesterol (7.1 mmol/l) and triglyceride (3.0 mmol/l) as cut-off points, 287 (46%) survivors were hyperlipidaemic. Hypercholesterolaemia with or without associated hypertriglyceridaemia was the commonest abnormality: 125 (20%) patients showed hypercholesterolaemia without associated hypertriglyceridaemia; 73 (12%) had both hypercholesterolaemia and hypertriglyceridaemia and 89 (14%) hypertriglyceridaemia without associated hypercholesterolaemia. The frequency of hyperlipidaemia did not vary with age. HDL cholesterol levels below 0.66 mmol/l (10th percentile) were observed in 131 (22%) survivors. Obesity was significantly more frequent among hypertriglyceridaemic survivors, whilst diabetes and hypertension were seen more frequently in survivors with combined hypercholesterolaemia and hypertriglyceridaemia. No significant difference was noted in the frequency of smoking and family history of coronary artery disease in hyperlipidaemia and normolipidaemic patients. PMID- 1889057 TI - Protective effect of preconditioning on reperfusion induced ventricular arrhythmias of isolated rat hearts. AB - STUDY OBJECTIVE: The aim was to investigate the effect of preconditioning on reperfusion induced arrhythmias in the isolated working rat heart. DESIGN: Rat hearts were perfused with modified Krebs-Henseleit bicarbonate buffer. A 15 min period of global ischaemia was performed followed by a reperfusion period of 5 min. This procedure was repeated three times. Hearts were divided into the control group (n = 10) and the free radical scavenger group (n = 11). Hearts in the latter were reperfused in the presence of scavengers (SOD 3.5 x 10(4) U.litre 1 and catalase 5.0 x 10(5) U.litre-1). EXPERIMENTAL MATERIAL: Hearts were obtained from male Sprague-Dawley rats (270-350 g). MEASUREMENTS AND MAIN RESULTS: The incidence of reperfusion induced ventricular fibrillation in the control group decreased from 100% to 70% (NS) and to 40% (p less than 0.01) during the second and the third reperfusion periods, respectively. In the scavenger group, the incidence of ventricular fibrillation was the same in each reperfusion period at 45%. The time to onset of ventricular fibrillation increased at the second reperfusion in both groups. CONCLUSIONS: (1) The protective effect of preconditioning on reperfusion induced arrhythmia is evident in the isolated rat heart. (2) Addition of free radical scavengers reduced the incidence of reperfusion arrhythmia. However, the protective effect of preconditioning was lost. PMID- 1889056 TI - Myocardial infarction during pregnancy: a case report. AB - Myocardial infarction during pregnancy is rare. This report presents a 28-year old parturient with no risk factors for coronary heart disease, in whom an acute anterior myocardial infarction occurred in the 34th gestational week. A cesarean section was performed at term due to an obstetrical cause and under hemodynamic monitoring without complications. Coronary angiography performed 4 months after delivery revealed the presence of normal coronary arteries and mild regional left ventricular dysfunction. PMID- 1889058 TI - Effects of digoxin, propranolol, and verapamil on exercise in patients with chronic isolated atrial fibrillation. AB - STUDY OBJECTIVE: The aim was to evaluate the effects of digoxin, propranolol, and verapamil on exercise in patients with chronic isolated atrial fibrillation. DESIGN: Patients with chronic isolated atrial fibrillation underwent maximal exercise testing before and after the administration of digoxin, propranolol, or verapamil. Heart rate, oxygen uptake and oxygen pulse were observed at rest, at gas exchange anaerobic threshold, and at peak exercise. SUBJECTS: The subjects were 10 patients (aged 48-78 years, mean age 60, SD 9, years) with chronic isolated atrial fibrillation. MEASUREMENTS AND MAIN RESULTS: During exercise without medication, the heart rate was 85 (SD 8) beats.min-1 at rest, 127(19) at the level of anaerobic threshold, and 175(17) at peak exercise. With digoxin, heart rate was reduced to 75(9) beats.min-1 at rest (control v digoxin, p less than 0.01). However, reduction of heart rate was not seen at anaerobic threshold or at peak exercise. With propranolol, heart rate was 63(7) beats.min-1 at rest, 99(16) at anaerobic threshold, and 138(28) at peak exercise (control v propranolol, all p less than 0.01). Heart rate with verapamil was 70(13) beats.min-1 at rest, 107(30) at anaerobic threshold, and 138(28) at peak exercise (control v verapamil, p less than 0.05 at rest and at anaerobic threshold, p less than 0.01 at peak exercise. Neither digoxin, nor propranolol, nor verapamil changed the oxygen uptake during exercise. Without medication, oxygen pulse was 6.5(2.0) ml.beat-1 at anaerobic threshold and 7.7(2.1) ml.beat-1 at peak exercise. With digoxin, the change of oxygen pulse, versus without medication, was not significant at rest or at anaerobic threshold but was increased at peak exercise, at 8.3(2.1) v 7.7(2.1) ml.beat-1, p less than 0.05. With propranolol, oxygen pulse was increased to 8.2(1.9) ml.beat-1 at anaerobic threshold and 9.2(2.3) ml.beat-1 at peak exercise (control v propranolol, both p less than 0.01). With verapamil, oxygen pulse was increased to 8.7(1.8) ml.beat-1 at anaerobic threshold and 10.0(2.1) ml.beat-1 at peak exercise (control v verapamil, both p less than 0.01). CONCLUSIONS: Digoxin was effective in reducing heart rate at rest, but failed to reduce it during exercise. Propranolol and verapamil reduced heart rate at all levels of exercise as well as at rest. Oxygen uptake during exercise (total exercise capacity) was not reduced with propranolol or verapamil; this was thought to have been accomplished by an increased oxygen pulse. PMID- 1889047 TI - Infectious diseases associated with complement deficiencies. AB - The complement system consists of both plasma and membrane proteins. The former influence the inflammatory response, immune modulation, and host defense. The latter are complement receptors, which mediate the cellular effects of complement activation, and regulatory proteins, which protect host cells from complement mediated injury. Complement activation occurs via either the classical or the alternative pathway, which converge at the level of C3 and share a sequence of terminal components. Four aspects of the complement cascade are critical to its function and regulation: (i) activation of the classical pathway, (ii) activation of the alternative pathway, (iii) C3 convertase formation and C3 deposition, and (iv) membrane attack complex assembly and insertion. In general, mechanisms evolved by pathogenic microbes to resist the effects of complement are targeted to these four steps. Because individual complement proteins subserve unique functional activities and are activated in a sequential manner, complement deficiency states are associated with predictable defects in complement-dependent functions. These deficiency states can be grouped by which of the above four mechanisms they disrupt. They are distinguished by unique epidemiologic, clinical, and microbiologic features and are most prevalent in patients with certain rheumatologic and infectious diseases. Ethnic background and the incidence of infection are important cofactors determining this prevalence. Although complement undoubtedly plays a role in host defense against many microbial pathogens, it appears most important in protection against encapsulated bacteria, especially Neisseria meningitidis but also Streptococcus pneumoniae, Haemophilus influenzae, and, to a lesser extent, Neisseria gonorrhoeae. The availability of effective polysaccharide vaccines and antibiotics provides an immunologic and chemotherapeutic rationale for preventing and treating infection in patients with these deficiencies. PMID- 1889059 TI - Ventricular fibrillation threshold is influenced by left ventricular stretch and mass in the absence of ischaemia. AB - STUDY OBJECTIVE: Ischaemic heart disease is known to contribute to the development of ventricular arrhythmias. However, the role of non-ischaemic variables has been less well defined. We therefore studied the effect of myocardial stretch and ventricular mass on the vulnerability of the rat heart to ventricular fibrillation. DESIGN AND EXPERIMENTAL MATERIAL: Two groups of rat hearts were studied in an isolated buffer perfused apparatus: group I, mature female animals with an average dry left ventricular weight of 73 mg and group II, a group of retired breeders with an average left ventricular weight of 122 mg. Hearts performed isovolumetric work at either low (0 mm Hg) or high (20 mm Hg) left ventricular end diastolic pressures. MEASUREMENTS AND MAIN RESULTS: Ventricular fibrillation was provoked by trains of ventricular extrastimuli delivered at increasing current until development of the arrhythmia. The current required to provoke ventricular fibrillation decreased in both groups at the high left ventricular end diastolic pressure and the larger hearts in group II were more vulnerable to ventricular fibrillation than those in group I. The decrease in ventricular fibrillation threshold occurred in the absence of an increase in myocardial lactate production or a decrease in endocardial to epicardial flow ratios. CONCLUSIONS: This study thus identified two variables, myocardial stretch and ventricular mass, which influence the development of ventricular fibrillation and which are independent of myocardial ischaemia in this animal model. These observations may be relevant to an understanding of the increased incidence of lethal arrhythmias which occur in patients with dilated cardiomyopathies. PMID- 1889060 TI - Adaptive mechanisms of the aorta and left ventricle to volume overloading following abrupt aortic regurgitation in rabbits. AB - STUDY OBJECTIVE: Compensatory mechanisms of the left ventricle for volume overloading caused by acute aortic regurgitation and associated changes in physiological properties of the aorta were studied in rabbits. DESIGN: Aortic regurgitation was produced by aortic valve perforation, and haemodynamic measurements were performed before, 1 h and 4 weeks afterwards. Characteristic impedance of the distensibility of the aorta were calculated. EXPERIMENTAL ANIMALS: 42 Japanese white rabbits were used. The animals were anaesthetised with intravenous urethane. MEASUREMENTS AND MAIN RESULTS: Total systemic vascular resistance did not change significantly during the 4 weeks. When aortic regurgitation was produced, an immediate increase in circumferential distensibility was followed by the gradual dilatation of the aorta. An increase in circumferential distensibility resulted in decreased characteristic impedance, and the reduction in cardiac output caused by aortic regurgitation was compensated by increased systolic shortening of left ventricular dimensions at 1 h. After 4 weeks, however, decreased characteristic impedance was associated with increased aortic diameters during both systole and diastole, and dilatation and hypertrophy of the left ventricle were responsible for compensation of left ventricular performance. CONCLUSIONS: Volume overloading of the left ventricle by aortic regurgitation gave rise to a two stage compensatory process over a 4 week period and the aorta interacted with chronological changes in left ventricular performance. PMID- 1889061 TI - Sequential echocardiographic-Doppler assessment of left ventricular remodelling and mitral regurgitation during evolving experimental heart failure. AB - STUDY OBJECTIVE: The aim was to study the nature, magnitude, and time course of left ventricular structural adaptations to evolving heart failure. DESIGN: 17 male mongrel dogs, weight 24.9(SD 3.7) kg, underwent rapid ventricular pacing (250 beats.min-1) until severe heart failure developed. Two dimensional echocardiographic and Doppler studies were performed at control, then weekly to severe heart failure. Haemodynamic measurements were made at control and severe heart failure. All studies were performed with the animals conscious during temporary sinus rhythm. MEASUREMENTS AND MAIN RESULTS: Left ventricular diastolic volume gradually increased and the left ventricle assumed a more globular shape associated with significant wall thinning. Both the change in diastolic volume after one week of pacing and at the time of severe heart failure correlated with the time to peak heart failure. Mitral regurgitation was mild after one week of pacing, became moderate in most animals at severe heart failure, and lagged temporarily behind the increase in cardiac dimensions. The percentage increase in mitral annular size was significantly less than the increase in left ventricular cross sectional area. CONCLUSIONS: In pacing induced heart failure (1) marked left ventricular remodelling occurs, (2) the extent of left ventricular dilatation, both early and late, correlates directly with the time required for the development of severe heart failure, (3) mitral regurgitation is an epiphenomenon and is most likely to be caused by the increase in left ventricular cross sectional area. PMID- 1889062 TI - The contribution of ischaemia to the development of microvascular incompetence in the myocardium. AB - STUDY OBJECTIVE: The aim was to determine the contribution of ischaemia per se to the development of microvascular incompetence in the myocardium. DESIGN: Isolated, buffer perfused rat hearts were made globally ischaemic for 0-60 min, then fixed with nitrogen bubbled glutaraldehyde and perfused with nuclear track emulsion to identify and quantify competent blood vessels in scanning and transmission electron micrographs. SUBJECTS: Adult Male Wistar rats weighing between 275 and 350 g were used. MEASUREMENTS AND MAIN RESULTS: Thirty or more min ischaemia significantly (p less than 0.05) reduced the density of competent capillaries in the subendocardial third of the myocardium, as did 45 or more min in the subepicardial third and 60 min in the middle third. Following 60 min ischaemia virtually all vessels in the subendocardial third were not perfusable. Severely ischaemic myocardium showed relatively normal, open, unobstructed capillaries and an absence of the endothelial, myocyte and mitochondrial swelling which have previously been attributed to ischaemia. CONCLUSIONS: In severely ischaemic myocardium microvascular incompetence shows a transmural gradient in severity. It develops progressively, starting near the endocardium. These findings suggest that postischaemic reoxygenation may accelerate the development of microvascular incompetence. PMID- 1889063 TI - Effects of diltiazem as an additive to St Thomas's Hospital cardioplegic solution in isolated neonatal and adult rabbit hearts. AB - STUDY OBJECTIVE: The aim was to compare the protective efficacy of diltiazem as an additive to St Thomas's Hospital cardioplegic solution in isolated hearts from neonatal and adult rabbits. DESIGN: The relative responsiveness of the two age groups to diltiazem was first determined in Langendorff perfused hearts (n = 6 per group) by constructing concentration-response curves for the drug's negative inotropic effect. The IC20 and IC50 of diltiazem (the concentrations of diltiazem resulting in 20% or 50% reduction in developed pressure, respectively) were the doses subsequently included in the cardioplegic solution. Isolated working hearts (n = 8 per group) were perfused aerobically (37 degrees C) for 20 min followed by a 2 min infusion of St Thomas's Hospital cardioplegic solution with or without added diltiazem. All hearts were then subjected to global ischaemia (37 degrees C). The durations of ischaemia were 60 min in the neonatal and 45 min in the adult heart. Hearts were then reperfused (15 min Langendorff, 20 min working) before reassessment of function. EXPERIMENTAL ANIMALS: 30 neonatal (7-10 d) and 30 adult (2-3 months) New Zealand white rabbits were used. MEASUREMENTS AND MAIN RESULTS: The IC20 and IC50 of diltiazem were found to be 0.1 and 0.5 mumol.litre 1, respectively, in the neonatal heart, and 0.5 and 2.5 mumol.litre-1, respectively, in the adult heart. Postischaemic recovery of cardiac output was 57.9(SEM 6.7)% in the control group and 64.1(5.0)% (NS) and 47.7(3.8)% (NS) in the 0.5 mumol.litre-1 and 2.5 mumol.litre-1 diltiazem groups, respectively, in the adult hearts. In the neonatal hearts, cardiac output recovered to 55.6(4.8)% in the control group and 59.9(4.2)% (NS) and 62.0(5.6)% (NS) in the 0.1 mumol.litre-1 and 0.5 mumol.litre-1 diltiazem groups, respectively. CONCLUSIONS: The addition of diltiazem, at IC20 or IC50 negative inotropic concentrations, to St Thomas's Hospital cardioplegic solution does not improve postischaemic recovery in either neonatal or adult rabbit hearts. This suggests that the slow calcium channel may not be an important mediator of ischaemia and reperfusion induced injury in the cardioplegically arrested rabbit heart. PMID- 1889064 TI - Effect of alpha adrenergic agents and phorbol esters on phosphorylation of sarcolemmal proteins in beating guinea pig hearts. AB - STUDY OBJECTIVE: The aim was to determine whether activation of protein kinase C by alpha adrenergic agonists or phorbol esters would be associated with increased phosphorylation of the 15 kDa sarcolemmal protein in guinea pig hearts. DESIGN: Intact, beating guinea pig hearts were perfused with modified Krebs-Henseleit buffer containing [32P]Pi and freeze clamped in a control condition or at the peak of the inotropic response to noradrenaline. Membrane vesicles enriched in sarcolemma were isolated and then subjected to SDS polyacrylamide gel electrophoresis and autoradiography. Phosphorylated proteins were identified and 32P incorporation was quantitated. In some cases, hearts were perfused with phorbol 12-myristate, 13-acetate, or dioctanoyl-glycerol, which are known to be potent activators of protein kinase C. EXPERIMENTAL PREPARATIONS: Whole hearts from 55 anaesthetised guinea pigs weighing 500-600 g were used. MEASUREMENTS AND MAIN RESULTS: Perfusion of guinea pig hearts with noradrenaline resulted in increases in contractility and tissue inositol 1,4,5-triphosphate levels, but there were no increases in the phosphorylation of the 15 kDa sarcolemmal protein observed. Furthermore, perfusion with phorbol 12-myristate, 13-acetate, or dioctanoylglycerol failed to stimulate the phosphorylation of the 15 kDa sarcolemmal protein. CONCLUSIONS: These data indicate that the 15 kDa sarcolemmal protein, which may be phosphorylated by protein kinase C in vitro, is not a substrate for the same enzyme in beating guinea pig hearts. PMID- 1889065 TI - Comparison of estimates of cardiac output by indicator dilution and freon 22 uptake during gas mixing in dogs. AB - STUDY OBJECTIVE: The aim was to measure cardiac output while rebreathing tidal volumes, by correction of soluble gas uptake for gaseous mixing. DESIGN: Simultaneous measurements of cardiac output by indocyanin green and freon 22 uptake during rebreathing were made. Mixing for a hypothetical gas of identical gaseous diffusivity to freon 22 was calculated by interpolation between concentrations of two insoluble gases, helium and sulphur hexafluoride. Mixing efficiency was estimated by the number of breaths for helium to become 99% equilibrated with lung gas (n99-He). EXPERIMENTAL MATERIAL: Five anaesthetised dogs rebreathed at intervals with 300 ml of test gas. MEASUREMENTS AND MAIN RESULTS: 63 comparisons of cardiac output using indocyanin green and freon 22 uptake (over breaths 7-13 using the mean mixed volume of distribution), gave a mean (95% confidence interval) underestimation of 0.345 (0.093-0.597) litre.min-1 (14%). Exclusion of 12 points in which n99-He was greater than 15 resulted in a mean underestimation of 0.052(-0.163-0.267) litre.min-1 (2%). Without correction for gaseous mixing, freon 22 uptake for these data overestimated blood flow by a mean of 1.31 litre.min-1 (overestimation = 2.7 over breaths 5-11). Use of the equilibrium volume of distribution resulted in an overestimation of blood flow relative to green dye of 1.2 litre.min-1 (breaths 5-11) and 0.76 litre.min-1 (breaths 7-13). CONCLUSIONS: Estimates of cardiac output by soluble gas uptake are optimal when correction is made for mixing of gas of identical diffusivity. The mean mixed gas volume gives the best correlation with the reference method, implying a selective distribution of blood flow to the better ventilated areas. PMID- 1889066 TI - Episodic cluster headache and narcolepsy: a case report. AB - A patient who first presented with episodic cluster headache later developed narcolepsy. In spite of REM sleep alterations associated with narcolepsy, the frequency and distribution of pain attacks did not change when narcolepsy occurred and were similar to those seen in cases of episodic cluster without narcolepsy. The lack of influence of narcolepsy on the pattern of cluster pains questions the role of REM sleep states in triggering pain in episodic cluster. PMID- 1889067 TI - Short-lasting unilateral neuralgiform headache attacks with tearing and conjunctival injection: the first "symptomatic" case? AB - A 36-year-old man was suffering from brief, unilateral and short-lasting pain attacks always associated with marked homolateral tearing and conjunctival injection, both presenting in a cluster fashion. An arteriovenous malformation was subsequently discovered in the homolateral cerebellopontine angle. The clinical picture shares similarities with both cluster headache and trigeminal neuralgia, although it can not be accurately placed with either of these forms. Patients with similar symptoms have previously been described in detail, and on the basis of these few descriptions a new syndrome "short-lasting" unilateral neuralgiform headache attacks with conjunctival injection, tearing, sweating, and rhinorrhoea has been postulated. Assuming the validity of this syndrome as an entity, this case is in all probability its first "symptomatic" example. Careful evaluation of the varieties of cluster headache and trigeminal neuralgia, and the reporting of similar new cases as they arise are necessary to establish the nosologic boundaries of this syndrome. PMID- 1889068 TI - A population-based analysis of the diagnostic criteria of the International Headache Society. AB - In 740 representative normal subjects a diagnostic headache interview and a neurological examination provided the necessary information to classify headache disorders according to the operational diagnostic criteria of the International Headache Society (IHS). Sixteen per cent (n = 119) had migraine, 78% (n = 578) tension-type headache. In migraineurs, pain was of a pulsating quality in 78%, severe in 85%, unilateral in 62%, and aggravated by routine physical activity in 96%. Tension-type headache was of a pressing quality in 78%, mild or moderate in 99%, bilateral in 90%, and 72% had no aggravation by physical activity. The accompanying symptoms of nausea, photo- and phonophobia occurred frequently and were usually moderate or severe in migraine subjects, and if present in subjects with tension-type headache, they were usually mild. Only two subjects had unclassifiable headache. The IHS Classification is thus exhaustive. The criteria may be improved by mandatory demands to the criterion of pain intensity leaving other features of pain as supportive for the diagnosis and by including graded severity of accompanying symptoms. A specific proposal is given. PMID- 1889069 TI - Multiple clinical and paraclinical analyses of chronic tension-type headache associated or unassociated with disorder of pericranial muscles. AB - Thirty-two female patients fulfilling the diagnostic criteria of chronic tension type headache underwent multiple clinical (severity index before and after biofeedback therapy; anxiety score) and paraclinical (pericranial EMG levels and pressure-pain thresholds, temporalis exteroceptive silent period) assessments. Twenty-three patients (72%) had at least one increased EMG level and/or at least one decreased pain threshold and qualified for the subgroup" associated with disorder of pericranial muscles" (code 2.2.1). Nine patients (28%) were within the normal range for both investigations and would have been classified in the subgroup "unassociated with such disorder" (code 2.2.2). No significant differences were found between these two groups of patients for headache severity, anxiety, response to biofeedback therapy or duration of temporalis second exteroceptive silent period. The various clinical and paraclinical parameters were not significantly correlated to each other. It is therefore suggested that the subdivision of chronic tension-type headache in two subgroups based on pericranial EMG levels and/or pain sensitivity might be artificial. Since both of the latter and temporalis silent periods vary independently, they appear complementary in the study of tension-type headache patients and probably represent peripheral abnormalities, which are induced to varying intensities by a common central nervous system dysfunction. PMID- 1889070 TI - Kinetics of platelet 5-hydroxytryptamine uptake in headache patients. AB - Platelet 5-hydroxytryptamine (5-HT) uptake was measured in asymptomatic headache patients attending a specialist migraine clinic, and in hospital staff who did not suffer from regular or severe headache. Current levels of anxiety and depression were assessed in all subjects using the Hospital Anxiety and Depression (HAD) scale and their possible influence on the uptake kinetics taken into account during the analysis of results. The Michaelis-Menten constant (Km) was significantly raised in common migraine and tension headache compared with controls (p less than 0.001 and p less than 0.01, respectively), but not in classical migraine or cluster headache. The increase remained significant after adjusting for differences in age, sex, presence of anxiety or depression (HAD sub scale score greater than or equal to 8), drug intake during the week before testing, time elapsed since last attack and time of assay (am or pm). No differences were observed between patients and controls in the maximal rate of uptake (Vmax) or platelet count, and previous reports of a reduction in Vmax in patients experiencing attack within 5 days prior to testing could not be confirmed. The cause and significance of an increased Km are not clear, but plasma factors acting as competitive inhibitors for the uptake site or an alteration in the configuration of the uptake site are possible explanations. If confirmed, the shared biochemical abnormality may suggest that common migraine and tension headache have a common pathogenesis. PMID- 1889071 TI - Magnetic resonance image abnormality in migraine with aura. AB - Cerebral magnetic resonance imaging (MRI) was performed on 18 patients with migraine characterized by aura consisting of both visual symptoms and paresthesias. Fifteen headache-free individuals of the same age range were used as controls. Records were randomized and read in blind fashion by two neuroradiologists. Small subcortical white matter lesions were seen in three migraine cases and two controls. In one migraine case cortical infarctions were seen. In two controls, small areas of increased density similar to those in migraine were seen. No consistent correlation of migraine or its duration with cerebral atrophy was found. It is concluded that identification of both these MRI findings (small subcortical white lesions and cerebral atrophy) as significantly associated with migraine is doubtful. PMID- 1889072 TI - Migraine with aura and photosensitive epileptic seizures: a case report. AB - An 18-year-old female presented with two seizures induced by photic stimulation. She had a positive family history for migraine and a history of febrile convulsions. Since the age of 13 she had suffered from migraine attacks with aura. A brain computerized tomography with contrast enhancement was negative and several electroencephalograms showed a photoparoxysmal response. At the age of 18 she had a partial secondary generalized seizure after photic stimulation during routine electroencephalogram. The onset of seizure was in the occipital region. Two days later, the patient presented with a typical migrainous attack with aura. Interictal apomorphine test (1.5 mg s.c.) blocked the photoparoxysmal response. According to Quesnay, dopaminergic failure of the occipital cortex may account for both epileptic and migraine features. PMID- 1889073 TI - C2 and C3 pain dermatomes in man. AB - This report defines the C2 and C3 pain dermatomes by the distribution of: the hypalgesia clearing after surgical root decompression; the dysaesthesias produced by electrical root stimulation; and the hypalgesia produced by anaesthetic root block. The C2 pain dermatome, so defined, consists of an occipital parietal area 6-8 cm wide, ascending paramedially from the subocciput to the vertex. The C3 pain dermatome is a craniofacial area including the scalp around the ear, the pinna, the lateral cheek over the angle of the jaw, the submental region and the lateral and anterior aspects of the upper neck. These C2 and C3 pain dermatomes do not overlap and are smaller than the C2 and C3 tactile dermatomes described in the literature. PMID- 1889074 TI - Complicated migraine studied by phosphorus magnetic resonance spectroscopy. PMID- 1889075 TI - A study on the exteroceptive suppression of the masseter, temporalis and trapezius muscles produced by mental nerve stimulation in patients with chronic headaches. PMID- 1889076 TI - Short and long term outcome of percutaneous transluminal coronary angioplasty in unstable versus stable angina pectoris: a report of the 1985-1986 NHLBI PTCA Registry. AB - In a cohort of 1,720 consecutive patients from the National Heart, Lung, and Blood Institute, Percutaneous Transluminal Coronary Angioplasty (PTCA) Registry (August 1985-May 1986), we compared 768 patients (45%) with stable angina and 952 patients (55%) with unstable angina pectoris. Unstable angina patients exhibited at least one of the following characteristics: new onset angina, rapidly progressing angina, angina at rest, angina refractory to medication, variant angina, acute coronary insufficiency, or angina recurring shortly after an acute myocardial infarct. The distribution of single- and multi-vessel disease was similar among stable and unstable angina patients; multi-vessel disease predominated. Average severity of stenosis and incidence of tubular and diffuse stenosis morphology were higher among patients with unstable angina (both p less than 0.001). Patient success rates were similar in stable and unstable patients. However, on a per lesion basis, overall angiographic success rate and average reduction of severity of stenosis in successfully dilated lesions were significantly higher among patients with unstable angina (both p less than 0.001). Incidence of major patient complications (p less than 0.01) and of emergency coronary bypass surgery (p less than 0.05) were also higher in patients with unstable angina but consistent with their more precarious clinical condition and stenosis morphology. During a two year follow-up, the cumulative distributions of death, myocardial infarct, repeat PTCA, and coronary bypass surgery were not significantly different in patients with stable angina compared to patients with unstable angina. Comparison of the current PTCA Registry cohort with the cases reported in the 1979-1982 Registry revealed a 19% higher success rate for both stable and unstable angina patients. Major complication rates decreased between time periods for stable but not for unstable angina patients. Incidence of emergency bypass surgery decreased more for stable than for unstable angina patients. Coronary angioplasty is indicated in properly selected patients with unstable angina and both single- and multi-vessel coronary disease. PMID- 1889077 TI - Percutaneous transluminal coronary angioplasty utilizing prolonged balloon inflations: initial results and six-month follow-up. AB - Coronary angioplasty (PTCA) using prolonged balloon inflation has obviated emergency coronary bypass surgery in some patients with acute occlusions at the time of PTCA. However, the use of prolonged balloon inflations has not been shown to improve long-term restenosis rates. As an alternative to the passive autoperfusion catheter, we evaluated a hemoperfusion system in which blood was obtained from the side arm of an arterial sheath and infused through the central lumen of standard balloon catheters via a modified Medrad IV pump during balloon inflation. PTCA was performed in 71 male patients (median age 57 yr). The median balloon inflation time was 4.8 minutes and the median rate of blood perfusion was 30 ml/min. PTCA was successful (lumen increase by 20 percentage points) in 83% of patients (59/71) with diameter stenosis decreasing from a median 82% to 30%. Emergency coronary bypass was required in four patients (5%). Angiographic data for six-month followup was available on 37 patients. The restenosis rate (loss of 50% of gain) was 46% (17/37). The conclusion is that prolonged balloon inflation angioplasty has a role in complicated PTCA but offers no advantage in improving long-term restenosis rates in elective PTCA. PMID- 1889078 TI - A femoral vein-femoral artery loop technique for aortic dilatation in children. AB - Balloon aortic dilatation is now a recognized therapy for aortic stenosis in children. Using retrograde approaches with either single or double balloons, successful dilatation can be readily achieved, but with little control of balloon position across the valve. We describe a femoral vein-femoral artery loop technique via a transseptal approach which facilitates antegrade crossing of the stenotic aortic valve and allows optimal balloon control and simultaneous pressure gradient recording during the procedure. PMID- 1889080 TI - Objective assessment of new technology. PMID- 1889079 TI - Blade atrial septostomy: experience with the first 50 procedures. AB - We have performed 50 blade and balloon atrial septostomies in 46 patients with diagnoses of transposition of the great arteries--32 patients; mitral atresia or stenosis--10 patients; total anomalous pulmonary venous drainage--2 patients; tricuspid atresia--1 patient; and pulmonary valve atresia with hypoplastic right ventricle--1 patient. The patients' age ranged from 1 day to 72 months (median = 8 months) and weights ranged from 2.7 to 14.5 kg. In patients with transposition the systemic saturation increased from an average of 62% to 74.6% (p less than 0.001) and the inter-atrial mean pressure gradient was reduced from 7.74 +/- 5.3 to 1.4 +/- 2.04 mm Hg. Patients with mitral atresia had no significant increase in systemic arterial saturation but a significant decrease in the mean inter atrial gradient from 19.6 +/- 12.4 to 3.8 +/- 5.3 mm Hg. In three patients the blade septostomy was unsuccessful for technical reasons and the condition of the patient. Complications included one death due to atrial laceration, blood loss requiring transfusion in 5 patients, transient CVA in one patient, and failure of the blade to close in one patient. We have found the palliative use of the blade catheter in conjunction with balloon atrial septostomy to be an effective and safe procedure. PMID- 1889081 TI - The NACI Registry: an instrument for the evaluation of new approaches to coronary intervention. The NACI Investigators. AB - The New Approaches to Coronary Intervention (NACI) Registry was developed to collect in-depth data about patients whose coronary artery lesions are being treated with new interventional techniques such as atherectomy, stents, and laser devices. The NACI Registry database distinguishes among several possible "modes" for device use, such as preparatory, planned definitive, and bailout use. Common definitions are used for data collection across all devices, and device-specific forms are used to record procedural details. NACI's unique modular form design facilitates thorough data collection, even for the most complex treatment scenarios. The database structure allows for data analysis at the patient, procedure, lesion, and device levels, as required to perform in-depth analyses of the immediate and long-term success of new devices. Once adequate knowledge of basic device performance has been collected, the Registry structure can also allow expeditious planning and performance of randomized trials comparing a new device to conventional PTCA. PMID- 1889082 TI - Abrupt vessel closure following platelet transfusion post-PTCA. AB - A successful PTCA was complicated by abrupt closure following a platelet transfusion which was given for control of local bleeding. Possible mechanisms of abrupt closure are discussed. Recommendation is made to avoid giving platelet transfusion following PTCA. PMID- 1889083 TI - Relationship between coronary blood flow and perfusion pressure during reactive hyperemia: a case report in an awake unanesthetized woman with normal coronary arteries. AB - The linear relationship between coronary blood flow and mean arterial pressure during reactive hyperemia is presented for the first time in an awake unanesthetized woman with normal coronary arteries during systemic hypotension induced by pharmacologic vasodilation. This case demonstrates the critical dependence of coronary flow reserve on simultaneous perfusion pressure. PMID- 1889084 TI - Percutaneous mitral valvuloplasty following surgical repair of sinus venosus atrial septal defect. AB - Mitral valvuloplasty performed 5 y after repair of a sinus venosus ASD was difficult because of a thickened septum, but resulted in improved mitral valve opening and did not lead to ASD. Thus, prior repair of a sinus venosus ASD may not be an absolute contraindication to mitral valvuloplasty. PMID- 1889085 TI - Ventricular fibrillation complicating endomyocardial biopsy of a cardiac allograft. AB - Transvenous endomyocardial biopsy remains the most useful diagnostic aid in assessing rejection in the transplanted heart. Although invasive, the complications associated with endomyocardial biopsy are few, and the procedure is generally regarded as safe. We report a case of apparent ventricular fibrillation complicating transvenous endomyocardial biopsy. Histologic section revealed evidence of moderate acute rejection. This case represents the first report of a life threatening ventricular dysrhythmia following routine endomyocardial biopsy in a cardiac transplant recipient. PMID- 1889086 TI - Mutational analysis of the interaction between CD4 and class II MHC: class II antigens contact CD4 on a surface opposite the gp120-binding site. AB - Using functional and adhesion assays, we have studied the ability of 30 human CD4 mutants to interact with class II major histocompatibility complex (MHC) molecules and also with gp120 from human immunodeficiency virus. The mutants cover the four domains (D1-D4) of CD4 and include several single-site substitutions. Analysis of the results, in the context of the CD4 crystal structure, shows that mutations that affect the interaction with class II MHC molecules are located on three exposed loops from CD4 domains 1 and 2. The specifically implicated residues, 19, 89, and 165, are separated from one another by 9 A, 24 A, and 24 A on one face of the CD4 molecule. Moreover, the class II binding site does not include residues 43 to 49 of the CD4 molecule, a region on an opposite face known to be involved in the binding of gp120. PMID- 1889087 TI - Friend virus-induced erythroleukemia and the multistage nature of cancer. PMID- 1889088 TI - Subtractive hybridization cloning of a tissue-specific extinguisher: TSE1 encodes a regulatory subunit of protein kinase A. AB - Tissue-specific extinguisher 1 (TSE1) is a trans-acting locus on human chromosome 17 that down-regulates expression of seven liver genes in hepatoma x fibroblast hybrids. To study the mechanism by which TSE1 functions, we used subtractive cDNA hybridization to clone transcripts encoded within a 2-4 Mb segment of chromosome 17 that includes TSE1. High resolution mapping within this region indicated that 8 of 9 different human cDNAs so obtained were distinct from TSE1. The remaining cDNA clone mapped concordantly with TSE1 in a panel of fragment-containing hybrids. DNA sequencing indicated that this cDNA encoded regulatory subunit RI alpha of cAMP-dependent protein kinase, and RI alpha mRNA levels correlated with TSE1 activity in various hybrid lines. Stable transfection of wild-type or cAMP binding mutant RI alpha alleles into hepatoma recipients produced an extinction phenotype indistinguishable from that encoded by human TSE1. We conclude that TSE1 encodes a regulatory subunit of protein kinase A whose activity differs in different cell types. PMID- 1889089 TI - The molecular basis of the undulated/Pax-1 mutation. AB - The murine paired box gene Pax-1 has been associated with the mouse developmental mutant undulated (un), which exhibits malformations in the vertebral column. In un mice, a point mutation leading to a Gly-Ser exchange in a conserved part of the paired domain of Pax-1 is present. Here we show that Pax-1 encodes a DNA binding protein with transcriptional activating properties. The DNA-binding specificity of the Pax-1 protein has been extensively analyzed in gel shift assays, and in conjunction with binding interference experiments, a DNA-binding core motif was defined. Comparison of the DNA-binding properties of wild-type and un Pax-1 proteins demonstrates that the Gly-Ser replacement at position 15 within the paired domain dramatically decreases the DNA-binding affinity of the un Pax-1 protein and alters its DNA-binding specificity. These results decipher the molecular basis of the un mutation. PMID- 1889090 TI - The Viviparous-1 developmental gene of maize encodes a novel transcriptional activator. AB - The Viviparous-1 (Vp1) gene of maize is specifically required for expression of the maturation program in seed development. We show that Vp1 encodes a 73,335 dalton protein with no detectable homology to known proteins. An acidic transcriptional activation sequence was identified by fusion to the GAL4 DNA binding domain. Expression of VP1 in maize protoplasts resulted in strong activation (greater than 130-fold) of a reporter gene fused to the promoter of a presumptive target gene. The acidic domain in VP1 was essential for transactivation and could be functionally replaced by the activator sequence of the herpes simplex virus VP16 protein. Our results indicate that VP1 is a novel transcription factor possibly involved in potentiation of a seed-specific hormone response. PMID- 1889091 TI - Activation of class II gene transcription by regulatory factors is potentiated by a novel activity. AB - A novel activity (USA) stimulated activator-dependent transcription in a reconstituted system in conjunction with natural TFIID, resulting in 10- to 50 fold levels of induction by regulatory factors. USA mediated a modest induction by USF in conjunction with either recombinant human TFIID, intact yeast TFIID, or the evolutionarily conserved C-terminal portion of yeast TFIID. Upon further purification, USA was resolved into two components that had opposite effects on core promoter activity and that in combination potentiated activator function. Gel mobility shift experiments indicated physical interactions between the inhibitory activity and TFIID, suggesting that the additional components (cofactors) associate with the preinitiation complex both to reduce promoter activity in the absence and to increase promoter activity in the presence of transcriptional activators. PMID- 1889092 TI - Influenza virus strain identification for the 1990-1991 influenza season. PMID- 1889093 TI - Distribution of influenza vaccine in Canada. PMID- 1889094 TI - Reye syndrome surveillance, 1989--United States. PMID- 1889095 TI - Cholera in 1990. PMID- 1889096 TI - Global Cholera Control Task Force. PMID- 1889098 TI - [Evaluation of nursing psychological traits]. PMID- 1889097 TI - Cholera. PMID- 1889100 TI - [Emergency treatment and care of acute Coriaria smica maxim poisoning]. PMID- 1889099 TI - [Sweeping methods of floors and beds in burn ward]. PMID- 1889101 TI - [Combination of commonly used antibiotics in intravenous infusions]. PMID- 1889102 TI - [Clinical and experimental study on cerebral thrombosis treated with antithrombotic xinmaining]. AB - Antithrombotic xinmaining were composed with Moschus, Calculus Bovis, Borneol, Radix Ligusticum, Flos Sophorae Immaturus, Radix Salviae Miltiorrhizae, Leech, etc. This preparation was suitable for treating channels and collaterals type of cerebral thrombosis. The dosage was 2-4 capsules (0.5 g/capsule) oral administration twice per day, 3-4 weeks as a therapeutic course. The authors studied 158 cases of these patients compared with 117 cases of control group with dextran and Vinorutone. The clinical result showed that the obvious effective rate in the therapeutic group was 62.1% and the total effective rate 96.3%; the values in the control group were 38.5% and 86.3% respectively (P less than 0.01). The laboratory results showed that the blood viscosity, serum viscosity, hematocrit (vol %), RBC electrophoresis rate (micron/sec/v/cm) and platelet aggregation rate (%) before antithrombotic xinmaining administration were 5.82 +/ 0.82, 1.82 +/- 0.02, 52.81 +/- 6.70, 0.82 +/- 0.19 and 28.33 +/- 12.02 respectively; and those after the treatment were 4.72 +/- 0.65, 1.70 +/- 0.02, 48.76 +/- 0.40, 0.97 +/- 0.17 and 23.05 +/- 10.01 (mean +/- S), P less than 0.01. The toxicological study proved that the preparation was safe, no significant side effect and good for cerebral thrombosis medication. PMID- 1889103 TI - [Clinical and experimental studies on the treatment of severe facioplegia with compressing drug, acupuncture and infrared rays]. AB - In 160 patients with severe facioplegia detected by the strength-duration curve, partial or complete reaction of degeneration of the facial nerve and its related muscles occurred in 158 patients and no reaction of degeneration in 2 patients. All the patients were arbitrarily divided into 2 groups. One group of 62 patients was treated with the regimen 1: Mianmasan adding acupuncture and the other of 98 patients with the regimen 2: modified Mianmasan adding acupuncture and red lighting. The treatment concretely was an application method by dusting the Mianmasan, over the scarified skin corresponding to the selected acupoints and motor points, and finally stick a piece of adhesive plaster on them. The clinical experiment was carried out by using double contrast method, i.e., autogenous and allogenic contrasts with ear pulse wave and skin temperature records. It was confirmed that the affected side of the face had chronic tissue ischemia and returned to normal after treatment. The results showed that among 160 treated patients, 70(43.8%) were cured, 46 (28.7%) markedly improved, 43 (26.9%) improved and 1 (0.6%) remained ineffective. By the statistical analysis, it was demonstrated that the curative effect of regimen 2 was superior to that of regimen 1 (P less than 0.01), and the effective rate in the patients with partial reaction of degeneration was higher than that in those with complete reactcon of degeneration (P less than 0.05). PMID- 1889104 TI - [Clinical research on the treatment of cervical spondylosis with jingtongning granule]. AB - The authors treated 102 cervical spondylosis patients with jing tong ning granule that made of herbs according to the TCM principle of promoting blood circulation to remove blood stasis. The 9 hemorheological indexes before and after treatment were observed. 15 patients of all were also observed the changes of eyeground microangium. Moreover, the animal experiments were taken in order to test and verify the effects further. The results revealed that the total effective rate was 96.1%. The main hemorheological indexes (eg. blood viscosity and plasma viscosity) showed significant difference in statistics before and after treatment (P less than 0.05, P less than 0.01). The changes of eyeground microangium had significant difference too, (P less than 0.01). The animal experimental results were the same as the clinical ones. Hence, the authors consider that jing tong ning granule had the effects to decrease the blood viscosity, improve microcirculation and accelerate blood flow. PMID- 1889105 TI - [Treatment of chemotherapy-induced leukocytopenia with acupuncture and moxibustion]. AB - The effects of acupuncture and moxibustion on 376 cases of chemotherapy-induced leukocytopenia was observed in patients with malignant tumors in the intermediary and advanced stages. Findings revealed that the total effect in 121 cases (88.4%) occurred in the group treated with acupuncture and moxibustion with warming needle; while the total effect in 221 cases (90.9%) was in the group treated with moxibustion with ignited moxa cone. A comparison made between the 2 groups showed no significant difference (P greater than 0.05). The total effective rate was 38.2% when compared with the control group using batylalcohol and pentoxyl and so the difference was significant (P less than 0.01). Analysis found that with patients having higher basic WBC value, the effect would be higher. Conversely, those who had lower basic value in their WBCs, the expected effect would be lower. These findings suggest that acupuncture and moxibustion in raising the effect on the white cells were influenced by the extent to which the bone marrow was inhibited, having no relevance to the kind of disease, the chemotherapy regime, and the treatment course which the patient was in. PMID- 1889107 TI - [Protective effect of Angelica injection on arrhythmia during myocardial ischemia reperfusion in rat]. AB - The protective effects of Angelica injection on arrhythmia were studied through the model of ischemic myocardial reperfusion in rats. The results showed that the incidence of ventricular premature beat and the total incidence of arrhythmia (IA) were greatly reduced by peritoneal injection of Angelica (0.6 gm crude drug/kg) in rats. The difference between the Angelica group (n = 12, IA = 41.7%) and the saline control group (n = 12, IA = 91.7%) was significant (P less than 0.05), while that between Angelica group and verapamil group (n = 10, IA = 40%) was insignificant (P greater than 0.05). The data suggested that Angelica injection is effective on the protection of arrhythmia during the myocardial ischemia reperfusion in rats. PMID- 1889106 TI - [Experimental studies on immunostimulatory effects of the Isatis indigotica polysaccharide]. AB - Polysaccharides extracted from the root of Isatis indigotica (IIP, 50 mg/kg.d, ipx8d) significantly increased the weight of spleen and number of white blood cell and lymphocyte in peripheral blood in normal ICR mice, and antagonized the immunosuppressive actions of hydrocortisone. There were marked potentiating effects on delayed hypersensitivity reaction induced by 2, 4-dinitrochlorobenzene in normal NIH mice treated with IIP as well as in immunodepressed mice induced by cyclophosphamide. By administration of IIP, the percentage of ANAE+ lymphocytes stained with acid alpha-naphthyl acetate esterase method were significantly increased in peripheral blood of normal ICR mice, and the decreases in number of ANAE+ lymphocytes in mice induced by hydrocortisone were prevented to a certain extent. But IIP could not enhance Con A-induced lymphocyte proliferation of C57BL mouse spleen cells in vitro measured with MTT colorimetric assay. In addition, the plaque forming cells in 5 x 10(6) splenocytes of NIH mice treated with IIP were higher than that of the control group (P less than 0.01). IIP could also elevate the clearance rate of intra-venous charcoal particles in normal mice, i.e., stimulated the phagocytic activity of macrophages. The result indicates that IIP is capable of increasing humoral and cellular immune functions and enhancing the functions of reticuloendothelial system, and might be a good immunopotentiator. PMID- 1889108 TI - [Scavenging effect of re-du-qing on free radicals]. AB - The general Shwartzman reactions of rabbits were induced by intravenously injecting endotoxin twice with 24 hours interval. The lipid peroxides (LPO) in sera and liver homogenates of rabbits in normal saline group (12.26 +/- 0.84 n mol MDA/ml, 1.86 +/- 0.43 n mol MDA/mg protein respectively) were significantly higher than those of rabbits in normal control group (7.93 +/- 2.90, 1.31 +/- 0.22, both P less than 0.01), and LPO in sera and liver homogenates of rabbits in Re-Du-Qing group (6.55 +/- 2.97, 1.19 +/- 0.12) were evidently lower than those of rabbits in normal saline group (P less than 0.01), accessed to the LPO level of rabbits in normal control group. In in vitro experiment, LPO of mitochondria in Re-Du-Qing group (1.50 +/- 0.43 n mol MDA/mg protein) dramatically decreased, compared with that of endotoxin group (2.39 +/- 0.69, P less than 0.05) and of control group (2.23 +/- 0.75, P less than 0.05). The findings of both in vivo and in vitro experiments showed that Re-Du-Qing possesses scavenging effect on free radicals. In view of the detoxification mechanism of Re-Du-Qing, in addition to inhibiting bacteria and degrading. endotoxin, the scavenging effect of Re-Du-Qing on free radicals are also included. PMID- 1889109 TI - [Treatment of idiopathic thrombocytopenic purpura with Chinese herbal drugs]. PMID- 1889110 TI - Pulmonary embolism: improving the odds. PMID- 1889111 TI - Ordering stool exams: room for improvement. PMID- 1889112 TI - Quo vadis, NIH? The new director plots a course. PMID- 1889113 TI - Immunoglobulin therapy in infectious disease. AB - The role of immunoglobulin therapy in the prevention and treatment of infectious disease has been greatly expanded by the ability to administer immunoglobulins intravenously. Neonates, patients with AIDS, and bone marrow transplant recipients are beneficiaries of the advances being made in IgG therapy. Studies suggest that the synergistic effect of a combination of antibiotics and antibodies will be useful in the future. Other future directions for antibody therapy include development of monoclonal antibodies for treatment of sepsis. Also, clinical trials of monoclonal antibody against tumor necrosis factor are setting the stage for monoclonal antibody research directed increasingly to the anti-mediator concept. PMID- 1889114 TI - Transesophageal echocardiography in the critical care unit. AB - Transthoracic echocardiography may be of limited value for patients in intensive care units because of suboptimal patient positioning, surgical wounds, and mechanical ventilation. By contrast, transesophageal echocardiography provides a new window for cardiac imaging, even in critically ill patients. We report our indications based on findings comparing transesophageal and transthoracic echocardiography in 112 studies in intensive care units. The transesophageal approach diagnosed 131 significant findings, compared to only 95 (73%) found transthoracically. Transesophageal echocardiography was superior to the transthoracic approach in patients with significant (higher than 2+) mitral regurgitation, with improved detection in 10 (9%) cases (p less than 0.05). Transesophageal echocardiography also provided additional information in the evaluation of vegetations, diseases of the aorta, visualization of the left ventricle, intracardiac masses, intracardiac thrombi, and congenital heart disease. Transesophageal echocardiography provides a useful diagnostic tool for evaluation of critically ill patients. PMID- 1889116 TI - Hepatic infarction: MRI appearance. AB - Because the liver is supplied with portal venous as well as hepatic arterial blood, hepatic infarction is a rare occurrence. Prior to the use of computed tomography (CT), ante mortem diagnosis of this entity was unusual. The CT findings in liver infarction have been described. However, the magnetic resonance imaging (MRI) appearance has not been well characterized or illustrated. We present the CT and MRI findings of a biopsy-proven case of hepatic infarction. PMID- 1889115 TI - Atrial fibrillation and flutter with left bundle branch block aberration referred as ventricular tachycardia. AB - Five patients were referred for electrophysiologic evaluation of nonsustained or sustained ventricular tachycardia. In each patient, the clinical rhythm disturbance was reproduced and identified as atrial fibrillation or flutter with left bundle branch block aberrancy. All five patients demonstrated enhanced or accelerated atrioventricular conduction through the normal atrioventricular nodal His Purkinje pathway. This rapid conduction created an electrophysiologic substrate suitable to the preferential development of this less common form of aberration. Four of five patients responded well (ventricular rate control or reversion to sinus rhythm) to verapamil therapy. Electrocardiographic criteria for differentiating supraventricular tachycardia with aberration from ventricular tachycardia exist. Nevertheless, misdiagnosis of wide complex tachycardia remains common. Electrophysiologic testing plays an important role in correctly identifying these rhythms, assessing long-term prognosis, and choosing effective therapy. PMID- 1889117 TI - Reversible decerebrate posturing after profound and prolonged hypoglycemia. AB - Decerebrate rigidity is one of several reversible neurological abnormalities which have been observed in the setting of metabolic coma. We present the case of a patient who recovered fully from prolonged decerebrate rigidity associated with hypoglycemic coma. This case emphasizes the possibility of recovery from severe, prolonged hypoglycemia. PMID- 1889118 TI - Estrogen supplements in menopause. PMID- 1889119 TI - Dressings for stasis ulcer. PMID- 1889120 TI - Aspirin and Reye's syndrome. PMID- 1889121 TI - Ionselective minielectrode determination of ionic and total calcium concentrations in mixed saliva. AB - A minielectrode suitable for determination of ionized and total calcium in small volumes (5 microliters or less) of biological fluids without loss of carbon dioxide from the sample, was evaluated. The relative standard deviation ranged from 4.5-7.1%, and analytical recovery from 97-101%. Interference by hydrogen, sodium and magnesium was negligible. Small differences in ionic strength between standards and samples caused only minor analytical errors. Freezing the sample prior to analysis significantly affected the readings for ionized calcium concentration. Compared to determination by atomic absorption spectrophotometry, there was no statistical difference in the total calcium concentration of mixed saliva determined by the electrode at approximately pH 4 after addition of a known volume of hydrogen chloride. This minielectrode method evaluated allows accurate calcium analysis of fluids such as secretion from minor salivary glands or the fluid in the dental integument, with subsequent recovery of the sample for further analysis. PMID- 1889122 TI - Glyceroluria in healthy adults, mentally ill adults and children selected for metabolic screening. PMID- 1889123 TI - Significance of variation in turnover of glycated albumin on indices of diabetic control. AB - We measured the half-time of disappearance of 125I-labelled glycated albumins in a rat model of diabetes with continuous infusion of physiological saline and insulin. Our results indicate that (i) in non-diabetic rats, continuous infusion of saline per se did not affect the concentrations of glucose or of fructosamine, and the half-time of disappearance of albumin was unaffected by degree of glycation; (ii) hyperglycaemia (mean plasma glucose concentration of 18-27 mmol/l) caused a small but significant increase in half-time of labelled glycated albumin disappearance from a mean of 42 h to a mean of 47 h; (iii) this effect of hyperglycaemia outweighed any effect of increase in albumin excretion detected in poorly controlled diabetic rats without infusion. We conclude that the effect of hyperglycaemia in slowing turnover of glycated albumin is likely to be insignificant in relation to its effect in promoting glycation, and may be species-dependent. However, in nondiabetics, variation of turnover of glycated albumin may well be significant in explaining the wide interindividual variation in concentration of glycated protein. PMID- 1889124 TI - Accelerated in vitro degradation of CCK-58 in blood and plasma of patients with acute pancreatitis. AB - Proteases released into the circulation during acute pancreatitis may hydrolyse circulating peptide hormones leading to altered regulatory functions. Cholecystokinin is a major regulator of postprandial gut function; stimulating pancreatic enzyme secretion, gallbladder contraction and diminishing food intake. Cholecystokinin-58 is the largest and most abundant form of this hormone in acid extracts of human intestine, and major amounts are released into the circulation after feeding. In order to test whether cholecystokinin-58 is degraded more rapidly due to the increased circulating of enzymes, this peptide was added to blood and plasma of patients with acute pancreatitis and incubated for various time intervals. The in vitro half life of cholecystokinin-58 was 10 +/- 1 minutes (mean +/- SE) in plasma and 11 +/- 1 min in blood from patients with acute pancreatitis, about four fold lower than the half life in plasma of healthy volunteers; 45 +/- 5 min. Degradation of cholecystokinin-58 produced immunoreactive forms of cholecystokinin that eluted in the positions of cholecystokinin-8 and cholecystokinin-33/39. We conclude that acute pancreatitis increases the degradation of CCK molecules. PMID- 1889125 TI - Serum aluminium and zinc and other variables in patients with and without cognitive impairment in the community. PMID- 1889126 TI - Changes in proteolytic susceptibility of erythrocyte membrane proteins in hereditary spherocytosis. PMID- 1889127 TI - Nomenclature standardization on an international basis. PMID- 1889128 TI - Primary localized cutaneous amyloidosis and familial medullary thyroid carcinoma. AB - We have studied a family with an autosomal dominant inheritance of primary localized cutaneous amyloidosis (PLCA) and familial medullary thyroid carcinoma (MTC). Ten family members were screened for multiple endocrine neoplasia (MEN) 2; five were found to have MTC and two had C-cell hyperplasia. None had evidence of phaeochromocytoma or parathyroid abnormalities. Five of these seven patients presented characteristic interscapular hyperpigmented lesions, showing dermal amyloid deposits in two of the four patients in which a biopsy was performed. The data are analysed in the light of two recent reports of MEN 2A associated with identical lesions. We conclude that PLCA should be sought in MTC patients, even if no other endocrinopathies are present. This may be informative of the familial character of MTC in index cases and also of the tumour gene status in family members who are being screened. PMID- 1889129 TI - Defects in monocyte polarization and dendritic cell clustering in patients with Graves' disease. A putative role for a non-specific immunoregulatory factor related to retroviral p15E. AB - A depressed chemotactic responsiveness of monocytes and a depressed cluster capability of dendritic cells have been found in diseases such as chronic purulent infections of the respiratory tract and in various types of malignancies. These impairments in monocyte and dendritic cell function could be ascribed to the action of a low molecular weight factor (LMWF; less than 25 kDa) circulating in the serum of the patients. The factor, which seems to be a non specific immunoregulatory factor, shares a structural homology with p15E, the capsular protein of murine and feline leukaemogenic retroviruses. In order to study the chemotactic responsiveness of monocytes and the cluster capability of dendritic cells of Graves' patients, monocytes were isolated from the peripheral blood and dendritic cells were prepared from these peripheral blood monocytes by exposure to metrizamide. Monocytes were studied for their chemotactic responsiveness measuring their capability to polarize (morphological changes determined by light microscopy) after stimulation with the chemoattractant fMLP. Dendritic cells were studied for their capability to form clusters with allogeneic lymphocytes. A defective fMLP-induced monocyte polarization was found (16 vs 37% in healthy controls), whereas the dendritic cells showed a defective clustering (60 clusters vs 151 clusters in healthy controls). The effect of fractions of less than 25 kDa prepared from the serum of Graves' patients on healthy donor monocytes and dendritic cells was studied to test the presence of p15E-like factors. The serum fractions had a significant inhibitory effect on monocyte polarization and dendritic cell clustering.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1889130 TI - Reproducibility of 24-hour serum growth hormone profiles in man. AB - OBJECTIVE: To study the reproducibility of 24-h serum growth hormone (GH) concentration profiles in adults. DESIGN: 24-h serum GH concentrations were constructed by drawing blood samples at 20-min intervals. Four study occasions over a period of 1 year were chosen to assess the reproducibility. SUBJECTS: Six healthy adult male volunteers of normal height and weight and aged between 20 and 22 years. MEASURES: The resulting GH data arrays were analysed by Fourier transformation. Between and within individual variations were calculated and expressed in terms of coefficients of variation and data plotted to show variations between groups and individuals. RESULTS: The frequency component of GH secretion occurred with a dominant periodicity of between 160 and 240 min. Precise estimates of spectral power (strength of oscillatory activity) and period were obtained for group data, but such estimates cannot be inferred from a single profile. There was no significant difference in 24-h mean serum GH concentration over the year of study: occasion 1 (February) mean 2.0 mU/l (SD 0.5); occasion 2 (March) mean 3.7 mU/l (SD 2.8); occasion 3 (July) mean 2.7 mU/l (SD 1.4); occasion 4 (February) 2.5 mU/l (SD 1.5) (mean within individual coefficient of variation 35%, range 9-58). The concentrations of factors known to influence GH synthesis and secretion, insulin-like growth factor I, thyroxine, testosterone and oestradiol, varied little over the year of study. CONCLUSIONS: These data demonstrate that group data are reproducible in terms of oscillatory activity and the amount of GH secreted and that 24-h GH profiles should be used predominantly for analysing group data. The variability between individual profiles limits their value in the investigation of children with growth failure and suspected GH insufficiency. PMID- 1889132 TI - The treatment of Cushing's syndrome. PMID- 1889131 TI - Changes in skeletal muscle and body composition after discontinuation of growth hormone treatment in growth hormone deficient young adults. AB - OBJECTIVES: The aim of this study was to determine whether there are any changes in skeletal muscle strength and size and body composition following growth hormone (GH) withdrawal in GH deficient young adults. DESIGN: A longitudinal, 1 year, open, uncontrolled study of the changes in skeletal muscle and body composition following GH withdrawal was performed. Endocrine status was reassessed at the end of the study period during an insulin tolerance test. Some measurements were repeated after 2 years of treatment. PATIENTS: Twelve (11 male, one female; age range 14-21) patients who had been diagnosed during childhood as growth hormone deficient took part in the study. Four of the 12 patients were found to have a normal GH response on retesting at the end of the study and their results were analysed as a separate group. MEASUREMENTS: Quadriceps and forearm flexor maximum voluntary isometric strength, body fat content and serum IGF-1 were measured at 3-monthly intervals over 1 year. Every 6 months muscle size was measured from computerized tomography scans and fibre area from quadriceps needle biopsy samples. RESULTS: For the growth hormone deficient group the 12 month quadriceps strength, size and fibre areas were 94.0% +/- 8.5 (mean +/- SD), 94.5% +/- 6.3 and 85.6% +/- 17.7 respectively of control (baseline) values. Forearm flexor strength and size were 101.4% +/- 7.9 and 92.0% +/- 9.2 of control. Body fat percentage had increased from 19.5% +/- 8.6 to 24.1% +/- 9.5. No change was seen in the non-growth hormone deficient group. CONCLUSIONS: Although the changes measured were relatively small they suggest a role for GH in the maintenance of muscle integrity and body composition in the young adult with growth hormone deficiency. PMID- 1889133 TI - The role of oxytocin: present concepts. PMID- 1889134 TI - Creutzfeldt-Jakob disease following treatment with human pituitary hormones. PMID- 1889135 TI - The management of obesity. PMID- 1889136 TI - Human plasma melatonin and urinary 6-sulphatoxy melatonin: studies in natural annual photoperiod and in extended darkness. AB - OBJECTIVES: The aims of the study were (1) to examine the human plasma melatonin rhythm at the equinoxes and the solstices in the natural photoperiod (at 35 degrees S); (2) to examine melatonin rhythms in the same subjects under extended darkness conditions to expose any suppressive (gating) effects of light at any time of the year; (3) to undertake a rigorous examination of the relationship between plasma melatonin and the urinary metabolite 6-sulphatoxy melatonin at varying times of the year. DESIGN: At the equinoxes and solstices, unrestricted subjects had hourly urine collections followed by venous blood sampling taken under natural light conditions for 24 hours. Following a 24 hour interval, a similar collection regime was performed with subjects held under conditions of extended darkness (5 hours darkness prior to natural sunset and following natural sunrise) for a further 24 hours. SUBJECTS: Groups of four (minimum) to six female volunteers (age range 18-35 years) were studied, who had a normal lifestyle, no history of depression, and were not taking any medication or recently engaged in shiftwork. MEASUREMENTS: The plasma was assayed for melatonin and the urine samples for 6-sulphatoxy melatonin by radioimmunoassay. RESULTS: The onset of natural melatonin secretion was delayed until after sunset at all seasons but was earlier in summer, and not different from the time of sunset in extended darkness. The offset of melatonin secretion under natural conditions occurred at sunrise in autumn and winter but was delayed until after sunrise during spring and summer, particularly in extended darkness. No significant changes in the duration of melatonin secretion were observed between seasons nor between the duration of melatonin secretion under natural photoperiod or extended darkness. The measurement of 6-sulphatoxy melatonin proved to be a close indicator of the phase and amplitude of secretion of plasma melatonin. Both onset and offset times of 6-sulphatoxy melatonin were delayed compared to the times when plasma melatonin was detectable/undetectable. A good correlation exists between the total plasma melatonin secretion and that of 6-sulphatoxy melatonin. CONCLUSIONS: The results suggest evidence for a suppressive (gating) effect of light at dawn only during summer which was associated with a phase advance of the onset of melatonin secretion at this time of year. The lack of a major gating effect of environment light on melatonin secretion, and the unchanging duration of secretion through the year in the normally entrained human, highlight differences between the human and those photoperiodic animal species which breed seasonally. Urinary 6-sulphatoxy melatonin proved to be a good indicator of plasma melatonin levels under rigorous examination and is confirmed as a useful clinical measure. PMID- 1889137 TI - Disturbance of osmoregulated thirst and vasopressin secretion in thyrotoxicosis. AB - OBJECTIVE: To assess the effect of untreated thyrotoxicosis on osmoregulated thirst sensation and AVP secretion. DESIGN: Measurements were made at 30-minute intervals while untreated thyrotoxic patients were given sodium chloride 855 mmol/l intravenously for 2 hours followed by water drinking ad libitum for 2 hours. The protocol was repeated when the patients were euthyroid. PATIENTS: Eight newly diagnosed thyrotoxic patients were studied. MEASUREMENTS: Thirst sensation (visual analogue scale), plasma osmolality, AVP and plasma renin activity were measured. RESULTS: Prior to osmotic stimulation and after plasma osmolality had been returned to normal by drinking water, thirst sensation was increased in the thyrotoxic state. Plasma AVP showed an exaggerated response to hypertonic saline in the patients when they were thyrotoxic. Increasing plasma osmolality produced a linear increase in thirst sensation and log linear increase in plasma AVP. However, in the thyrotoxic state both these relations were altered. The apparent osmolar thresholds for onset of thirst sensation and AVP release were similar (281 and 280 mosm/kg respectively) and were reduced similarly in the thyrotoxic state (269 and 274 mosm/kg respectively). CONCLUSIONS: The osmostat mechanisms which regulate thirst sensation and AVP release are reset in the thyrotoxic state. The responses of thirst sensation and of plasma AVP to increasing plasma osmolality are altered similarly, suggesting that thyrotoxicosis affects both homeostatic functions by a common mechanism. PMID- 1889138 TI - Prevalence of thyroid deficiency in pregnant women. AB - OBJECTIVE: The present study was designed to determine the current prevalence of gestational hypothyroidism, since maternal thyroxine deficiency is associated with poor obstetric outcomes and mental retardation in the surviving offspring. DESIGN: TSH concentrations were measured in the sera of women at 15-18 weeks of gestation. Those sera with TSH concentrations above 6 mU/l and the two sera closest in order with TSH concentrations below 6 mU/l were further analysed for T4, FT4, TBG, and antithyroid antibodies. Study criteria for hypothyroidism were sera with elevated concentrations of TSH plus both a free T4 concentration and a total T4 concentration and/or T4/TBG ratio more than two standard deviations below the mean for the control pregnant women. PATIENTS: The sera were from 2000 consecutive women in Maine being tested for alpha-fetoprotein concentration at 15 18 weeks of gestation. RESULTS: TSH concentrations above 6 mU/l were found in the sera of 49 women, 2.5% of the pregnant women. Six women with elevated TSH concentrations (range 6.9-54 mU/l) had both a FT4 concentration and a T4/TBG ratio and/or a T4 concentration more than two standard deviations below the respective control means, meeting the study criteria for thyroid deficiency, and thus giving a prevalence of 0.3%. The remaining 43 women with elevated TSH concentrations were classified as having compensated thyroid disease although some may have been hypothyroid. Fifty-eight per cent of women with TSH concentrations above 6 mU/l and 90% of the women with elevated TSH concentrations and at least one thyroxine index more than two standard deviations below the control means had positive titres of antithyroid antibodies as opposed to 11% of the controls. CONCLUSIONS: Although it is not known what severity of maternal thyroid deficiency is necessary to cause fetal brain damage, the present data indicate a sufficiently high prevalence of thyroid dysfunction to demand investigation of the mental development of the offspring of women with thyroid dysfunction and of the effect of replacement therapy. PMID- 1889139 TI - The use of venous catheterization in the diagnosis and localization of bilateral phaeochromocytomas. AB - OBJECTIVE: The purpose was to assess the value of venous catheter sampling as a method for the location of phaeochromocytomas, particularly when imaging techniques have been equivocal or ambiguous. DESIGN: Venous catheter sampling was carried out in cases of suspected phaeochromocytoma, and compared with samples obtained from other patients without phaeochromocytomas undergoing adrenal venous catheterization. PATIENTS: Three patients had phaeochromocytomas (subsequently confirmed by histology); five patients had no clinical or biochemical evidence of phaeochromocytoma but were being investigated for other conditions. MEASUREMENTS: Catecholamine and cortisol assays were performed on plasma samples from the adrenal veins and elsewhere, and the noradrenaline to adrenaline (NA:AD) ratio was calculated. RESULTS In patients without phaeochromocytomas the NA:AD ratio was less than 1 in nine adrenal vein samples; in four adrenal vein samples with NA:AD ratio of greater than 1, the presence of a phaeochromocytoma was subsequently confirmed. An extra-adrenal tumour was also located by comparison of central and peripheral venous catecholamine concentrations. CONCLUSIONS: Venous catheterization with measurements of catecholamines, and determination of NA:AD ratios, allows for the rapid and confident diagnosis and localization of unilateral, bilateral, and extra-adrenal phaeochromocytomas. PMID- 1889140 TI - Nocturnal melatonin secretion in thyroid disease and in obesity. AB - OBJECTIVE: The purpose was to investigate whether the function of the pinealocytes is changed in patients with disturbed metabolic rate or in subjects with marked obesity. DESIGN: Venous blood was sampled every second hour between 1800 and 0800 h, and urine collected between 2200 and 0700 h. PATIENTS: Eight patients with thyrotoxicosis, six with primary hypothyroidism, eight with maturity-onset obesity, and 12 healthy controls were included in the study. MEASUREMENTS: Peak serum melatonin values during the night, total nocturnal melatonin secretion (estimated by melatonin incremental areas), and urinary excretion of melatonin were determined in each participant. RESULTS: Patients with hypothyroidism were found to have higher peak serum melatonin values, total nocturnal melatonin secretion, and urinary excretion of melatonin than normal individuals (Peak melatonin values: 0.55 +/- 0.13 vs 0.27 +/- 0.04 nmol/l, respectively; P less than 0.05. Melatonin incremental areas: 3.38 +/- 0.80 vs 1.45 +/- 0.26 nmol/l h; P less than 0.05. Melatonin excretion: 0.140 +/- 0.023 vs 0.081 +/- 0.013 nmol/9 h; P less than 0.05). Neither of these values differed significantly from the normal in patients with thyrotoxicosis or obesity. Although thyrotoxic patients thus released a normal amount of melatonin during the night, their melatonin secretion peak was phase advanced (melatonin secretion peak appearing at 1.1 +/- 0.5 h in thyrotoxic, and at 3.4 +/- 0.5 h in normal participants; P less than 0.01). No such phase shifts were seen in patients with obesity or hypothyroidism. CONCLUSIONS: These findings imply that both hypothyroid and thyrotoxic patients have disturbed pineal function, which is not the case in patients with obesity. The mechanism underlying these observations remains to be elucidated. PMID- 1889141 TI - Changes in circulating thyroid hormone levels and systolic time intervals in acute hypothyroidism. AB - OBJECTIVE: We have previously reported that, in thyrotoxic patients treated with carbimazole, serum T4 and T3 levels are the first parameters to return to normal, followed by the systolic time interval (STI, a marker of thyroid function at tissue level) and then the serum TSH. The aim of this study was to compare the rate of change of thyroid hormones, TSH and STI in treated hypothyroid patients after the sudden withdrawal of thyroxine. DESIGN AND PATIENTS: Serum T4, T3 (free and total) and TSH were measured in 12 patients taking thyroxine for primary hypothyroidism; seven were biochemically euthyroid and five were over-replaced, as defined by an elevated free T4 and a sub-normal TSH. Thyroxine was withdrawn and the measurements repeated three times a week until the STI rose above the euthyroid range (0.26-0.32). RESULTS: After stopping thyroxine, the serum TSH and STI left the normal range, in advance of the free T4 and T3, after 9.5 +/- 0.95 and 12.2 +/- 1.5 days respectively (mean +/- SEM). The TSH was the first parameter to leave the euthyroid range in all subjects except one in whom the serum TSH was fully suppressed (less than 0.05 mU/l) initially. In the euthyroid group the TSH and STI increased rapidly after stopping thyroxine (time to leave euthyroid range 7.4 +/- 0.8 and 9.4 +/- 0.7 days respectively). In contrast, in the over-replaced group serum TSH and STI became elevated after 12.4 +/- 1.0 days (P less than 0.005 vs euthyroid group) and 16.0 +/- 2.7 days (P less than 0.05 vs euthyroid group) respectively. There was no delay in the fall in serum T4 or T3 in the over-replaced group when compared with the euthyroid group. CONCLUSIONS: In the evolution of primary hypothyroidism, markers of thyroid function at a tissue level (TSH and STI) become abnormal in advance of thyroid hormones. After stopping thyroxine therapy in treated hypothyroid patients, there is a delayed rise in STI and serum TSH levels in subjects with a subnormal TSH level, as compared with those with a normal TSH on treatment. This suggests mild tissue thyrotoxicosis in these individuals. PMID- 1889142 TI - Glucocorticoid receptors in lymphocytes in anorexia nervosa. AB - OBJECTIVE: The aim was to explore the down-regulation of the glucocorticoid receptors during hypercortisolaemia in anorexia nervosa. DESIGN: Urine and plasma samples were obtained for cortisol determination and blood lymphocytes were isolated for receptor binding studies. PATIENTS: Sixteen anorexic patients, aged 16-27 years, with a mean +/- SEM body mass index of 14.2 +/- 2.0 (ranging from 11.1 to 17.4), and 15 normal women were studied. Six patients were reinvestigated after a significant weight gain. MEASUREMENTS: The binding capacity and affinity of the glucocorticoid receptors were measured with dexamethasone as ligand on lymphocytes. RESULTS: In patients, both total and free plasma cortisol concentrations were higher than in the normal women, as was their urinary free cortisol; the number of glucocorticoid receptors per cell (Ro) and the binding affinity (Kd) for dexamethasone were, however, not significantly different (Ro: 7687 +/- 1750 vs 7347 +/- 1285 sites/cell; Kd: 7.7 +/- 2.4 vs 7.4 +/- 1.7 nM at 24 degrees C). After weight gain (14 +/- 2 to 16 +/- 2 kg/m2), receptor numbers were 8421 +/- 2126 (pre) and 9011 +/- 500 (post) sites/cell, which are not significantly different (P greater than 0.2); the Kd was unchanged (9.3 +/- 2.6 vs 9.2 +/- 2.4 nM). CONCLUSIONS Hypercortisolaemia does not down-regulate the lymphocyte glucocorticoid receptors in anorexia nervosa and a post-receptor defect might be involved in peripheral tissue resistance to the effects of glucocorticoid hormones in undernutrition. PMID- 1889144 TI - Association between autoimmune thyroid disease and familial Alzheimer's disease. AB - OBJECTIVE: To determine the prevalence of autoimmune thyroid disease in Familial Alzheimer's Disease kindreds and to ascertain whether there is any evidence for genetic linkage between the two conditions. DESIGN: Retrospective study of Familial Alzheimer's Disease kindreds. PATIENTS: Seventy affected and unaffected family members from 12 kindreds. MEASUREMENTS: Anti-thyroglobulin and anti microsomal autoantibody status was determined using an enzyme-linked immunosorbent assay. Thyrotrophin levels were determined by an immunoradiometric assay. RESULTS: Of the family members, 41.4% had evidence of autoimmune thyroid disease, with significant co-segregation between the presence of thyroid autoantibodies and the development of Alzheimer's disease (P less than 0.01). CONCLUSIONS: This study demonstrates a very high prevalence of autoimmune thyroid disease in Familial Alzheimer's Disease kindreds and suggests that a genetic factor contributing towards the development of autoimmune thyroid disease may be located on chromosome 21 within close proximity to the Familial Alzheimer's Disease gene. PMID- 1889143 TI - Cholinergic blockade with pirenzepine induces dose-related reduction in glucose and insulin responses to a mixed meal in normal subjects and non-insulin dependent diabetics. AB - OBJECTIVE: The aim of the study was to assess the effects of cholinergic blockade with pirenzepine on glucose and insulin responses to a mixed meal in normal subjects and patients with non-insulin dependent diabetes (NIDDM). Further, to assess in normal subjects the relative importance of nocturnal GH suppression by pirenzepine. DESIGN: Placebo, 100 or 200 mg pirenzepine were given to the normal subjects 1 hour before a standard mixed meal. The effects of placebo or 200 mg pirenzepine at night on nocturnal GH secretion and subsequent breakfast carbohydrate tolerance were also studied. NIDDMs were given placebo or 200 mg pirenzepine before the meal. SUBJECTS: We studied six healthy male volunteers (ages 20-22, body mass indices 20.3-23.3) and ten NIDDMs (eight men, ages 42-74); five obese (BMI 25.5-31.8) and five non-obese (BMI 21.2-24.8). MEASUREMENTS: Serial plasma glucose and insulin concentrations were measured for 3 hours after a standard mixed meal. RESULTS: Acute pretreatment of normal male volunteers with pirenzepine produced a dose-related improvement in carbohydrate tolerance. Peak post-prandial plasma glucose levels were delayed and significantly reduced following 200 mg orally (6.5 +/- 0.1 mmol/l), but not following 100 mg (7.3 +/- 0.3), compared with placebo (7.6 +/- 0.3). Peak insulin levels were similarly delayed and reduced by the 200 mg dose only (36.5 +/- 6.1 mU/l, compared with 49.8 +/- 8.7). Suppression of nocturnal GH by 200 mg pirenzepine at night produced a small reduction in fasting plasma glucose (5.0 +/- 0.1 mmol/l, compared with 5.3 +/- 0.1, P less than 0.02) but did not improve subsequent breakfast carbohydrate tolerance. Peak plasma glucose in NIDDMs was reduced following pirenzepine (12.4 +/- 0.9 mmol/l) compared with placebo (14.3 +/- 1.0, P less than 0.01). This reduction was equally significant in obese and non-obese groups. Peak plasma insulin was also reduced by pirenzepine (22.4 +/- 3.9 mU/l) compared with placebo (42.4 +/- 5.3, P less than 0.01). Insulin suppression was quantitatively greater in obese than in non-obese patients. CONCLUSIONS: Improvement in carbohydrate tolerance after pirenzepine in normal subjects is dose related and largely independent of GH suppression. Cholinergic blockade can also improve meal carbohydrate tolerance with simultaneous reduction in plasma insulin concentrations in non-insulin dependent diabetics, particularly those with obesity. PMID- 1889145 TI - An association between hypothalamic-pituitary dysfunction and peripheral endocrine function in extreme obesity. AB - OBJECTIVE: The aim was to investigate a possible relationship between measures of insulin secretion and glucose disposal and hypothalamic-pituitary function in extreme obesity. DESIGN: A cross-sectional analysis of obese subjects attending the Obesity Clinic at the Royal London Hospital and normal weight volunteers was undertaken. Investigations were performed on separate occasions and in random order. PATIENTS: The subjects were 34 extremely obese women, menstruating and with normal glucose tolerance (mean Body Mass Index, BMI = 42) and 15 normal weight female controls (mean BMI = 22). MEASUREMENTS: The following were measured: fasting insulin, relative insulin resistance calculated using fasting insulin and plasma glucose by the homeostatic model of assessment, insulin release during a 75-g oral glucose tolerance test (insulin area under the curve), steady-state plasma glucose level achieved during a simultaneous intravenous infusion of dextrose, insulin and somatostatin, and the prolactin and growth hormone (GH) responses to insulin-induced hypoglycaemia. RESULTS: In the obese group an impaired prolactin response to hypoglycaemia (mean area under the curve obese 54 U/l min, controls 155 U/l min; P = 0.0001) was inversely correlated to fasting insulin, r2 = 0.142, P = 0.03; relative insulin resistance, r2 = 0.134, P = 0.03 and steady-state plasma glucose level, r2 = 0.345, P = 0.0004 whereas the impaired GH response (mean GH area under the curve obese 1.9 U/l min, controls 65.7 U/l min; P = 0.0001) was inversely correlated to steady-state plasma glucose level, r2 = 0.196, P = 0.01. Backward procedure for stepwise regression analysis confirmed the steady-state plasma glucose level to be the most important variable associated with the prolactin and growth hormone response among the remaining indices of insulin secretion/resistance. CONCLUSION: We conclude from these findings that hyperinsulinaemia in obesity is an important association with altered hypothalamic-pituitary function indicated by impaired prolactin and growth hormone secretion to insulin-induced hypoglycaemia. PMID- 1889146 TI - C4A deficiency and poor prognosis in patients with IgA nephropathy. AB - IgA nephropathy (Berger's disease) is an important cause of end-stage renal failure in persons of Asian and European descent. We performed C4 phenotyping on plasma from 123 patients with IgA nephropathy who resided in several different parts of the United States. All of these patients underwent diagnostic renal biopsy in adulthood. Six patients had a total deficiency for the C4A protein and all six had chronic renal insufficiency (serum creatinine concentration higher than 1.4 mg/dl at last follow-up). In contrast, 47% of the patients without C4A deficiency had chronic renal insufficiency (p = 0.001). The C4 gene defect was due to deletion of both C4A genes in only two individuals, whereas three patients were heterozygous for the C4A gene deletion. We speculate that the functional alteration of the complement system related to C4A deficiency might lead to expression of clinically severe disease in an individual with a genetic susceptibility to IgA nephropathy. PMID- 1889147 TI - Autoreactive lymphocytotoxic IgM antibodies in highly sensitized dialysis patients waiting for a kidney transplant: identification and clinical relevance. AB - The contribution of different families of lymphocytotoxic antibodies in the serologic reactivity of 45 highly sensitized dialysis patients (HSDP) (panel reactivity antibody value-PRA greater than 80%) was assessed by analyzing patients' sera for the presence of auto- and alloreactive IgM and alloreactive IgG antibodies. A total of 220 sera was screened at different incubation temperatures, before and after treatment with the reducing agent dithiothreitol, against a large variety of cell targets by means of complement dependent cytotoxicity (CDC) and antiglobulin augmented (AHG) CDC assays. The results allowed to subdivide the HSDP under study into four groups: Group 1 consisted of 13 untransplanted patients and 14 patients with a prior failed graft whose PRA values did not change following DTT treatment. Alloreactive IgG antibodies alone, with anti-HLA specificity, were present in the sera of this patient group. Group 2 consisted of 3 untransplanted patients whose sera did not contain any autolymphocytotoxic antibody but appeared completely unreactive to panel lymphocytes following DTT treatment, thus confirming the presence of alloreactive IgM only endowed with antiHLA reactivity. Group 3 consisted of 4 untransplanted and 4 patients with a prior failed graft whose sera were found to contain in addition to autoreactive IgM also alloreactive IgG antibodies. Their PRA values declined after DTT treatment on average from 96.2% to 45% and from 95% to 52.5%, respectively. Group 4 consisted of 6 untransplanted patients whose PRA reactivity to both autologous and panel lymphocytes completely disappeared following DTT treatment, thus indicating that their sera contained exclusively autolymphocytotoxic IgM antibodies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1889148 TI - An analysis of ten-year trends in infections in adults on continuous ambulatory peritoneal dialysis (CAPD). AB - Infectious complications are the Achilles heel of CAPD. To determine trends in these events, we analyzed the CAPD related infections of 303 adults on CAPD at a single university center between 1979 and 1989. During this decade the percentage of insulin-dependent diabetics increased from 14% to 39% (p less than 0.005). Peritonitis rates fell from 2.4 episodes/y in 1979 to 0.8 episodes/y in 1989. The proportion of patients with multiple episodes of peritonitis decreased (40% of the patients in 1979-1982 vs 15% in 1983-1989, p = 0.0001) while the proportion of patients with no episodes of peritonitis increased during the same periods (29% vs 49%, p = 0.005). The proportion of peritonitis episodes due to S. aureus rose over the 10-year period (p = 0.005), while those due to S. epidermidis decreased (p less than 0.10). The overall incidence of S. aureus peritonitis remained unchanged. Catheter infection rates initially increased and then fell during the decade; S. aureus remained the predominant cause. The proportion of peritonitis episodes associated with catheter infection rose (13% in 1982 vs 24% in 1989, p = 0.025), and in 1989, 80% of these episodes were caused by S. aureus. Catheter loss was also primarily due to S. aureus infections in 1989 (80%). Infections due to P. aeruginosa were a persistent problem. The proportion of patients transferring to hemodialysis each year paralleled catheter loss rates, which in turn appeared to be more related to catheter infection rates than to peritonitis rates. We conclude that control of S. aureus and P. aeruginosa will be the key to future reductions in the infectious complications of CAPD patients. PMID- 1889149 TI - Pharmacokinetics of vancomycin in patients undergoing hemodialysis with polyacrylonitrile. AB - The pharmacokinetics of vancomycin in patients undergoing dialysis with cuprophane membranes are well known, however little has been reported of the use of polyacrylonitrile membranes in dialysis. We studied, in a crossover design, eight dialysis patients (7 men, 1 woman) aged 30 to 66 years who prospectively received 1 gram of vancomycin i.v. before first dialysis and were subsequently hemodialyzed with cuprophane every second day for a total of three times. A month later trial was repeated using polyacrylonitrile. A mono-compartment model was used to calculated pharmacokinetic parameters. Mean +/- standard deviation of vancomycin clearance varied from 5.2 +/- 2.1 ml/min in the interdialysis period to 9.7 +/- 2.7 ml/min during dialysis with cuprophane and to 58.4 +/- 15.6 ml/min during dialysis with polyacrylonitrile (p less than 0.001). Vancomycin half-life varied from 71.5 +/- 23.0 to 35.9 +/- 9.8 and to 6.1 +/- 1.4 hours, respectively (p less than 0.001). Fractional removal of vancomycin increased from 4% using the cuprophane dialyzer to 34% using the polyacrylonitrile dialyzer (p less than 0.001). Serum vancomycin levels at 100 and 168 hours were higher with cuprophane than with polyacrylonitrile (7.0 +/- 2.2 vs 3.9 +/- 1.2 micrograms/ml) (p less than 0.001). Moreover, the mean levels at 100 hours were suboptimal on polyacrylonitrile. Approximately 208 +/- 53 mg of vancomycin were removed during one polyacrylonitrile dialysis. Thus, those patients who undergo dialysis with polyacrylonitrile and are treated with vancomycin may need supplementary doses post dialysis or to lessen dosage intervals than those traditionally used for dialysis patients since clearance of the drug is significantly higher than with cuprophane dialyzers. Continuous monitoring of vancomycin levels is also recommended. PMID- 1889150 TI - Acute thrombosis of the renal transplant artery: a case report and review of the literature. AB - Acute thrombosis of the renal transplant artery is a known but unusual complication of renal transplantation usually occurring in the first month. Reported here is a case of acute renal artery thrombosis in a well functioning long-term renal allograft in which there was clear angiographic evidence of a normal renal artery two years earlier. PMID- 1889151 TI - Diffuse mesangial sclerosis in a fetus. AB - An 18-week fetus was born following termination of pregnancy by prostaglandin induction. Pregnancy was terminated because of elevated maternal serum alpha fetoprotein and ultrasonographic evidence of severe oligohydramnios, intrauterine growth retardation, non-visualization of the bladder, dolichocephaly and possible mild hydrocephalus. Pathologic examination disclosed diffuse mesangial sclerosis and histologic evidence of the nephrotic syndrome. To our knowledge this is the first reported example of ante-natal diffuse mesangial sclerosis; of fetal congenital nephrosis other than Finnish type; and of fetal congenital nephrosis with prominent glomerular lesions. PMID- 1889152 TI - Peritonitis caused by Candida lusitaniae in patient on continuous ambulatory peritoneal dialysis (CAPD) PMID- 1889153 TI - Treatment of nephrotic hyperlipidemia with lovastatin. PMID- 1889154 TI - Pattern of proteinuria in IgA nephritis by SDS-PAGE: clinical significance. AB - Of sixty patients with IgA nephritis, none had CRF at first examination, 13 developed CRF with creatinine above 1.6 mg/dl within 6 years. Among these patients who had analysis of proteinuria by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE), 31 patients had middle molecular weight (MMW) proteinuria alone (pattern 1), 10 had MMW and Low MW (LMW) or tubular proteinuria (pattern 2), 10 had high MW (HMW) and MMW proteinuria (Pattern 3) and 9 had HMW, MMW and LMW proteinuria (Pattern 4). At the end of a follow up period of 6 years (1983-1989) patients with mixed proteinuria had a higher incidence of chronic renal failure (CRF), 11/29 (38%) compared to those with pattern 1 proteinuria, 2/31 (6%) (chi 2 = 8.7, p less than 0.005). Based on the glomerular selectivity index (GSI), 19 patients had nonselective proteinuria but they did not have a higher incidence of CRF. By the selectivity index (SI), 18 patients had nonselective proteinuria and they showed a significantly higher incidence of CRF. Compared to the 41 patients who did not have LMW proteinuria, 19 patients with LMW proteinuria had more severe proteinuria. After a follow-up period of 6 years, patients with LMW proteinuria had a higher incidence of CRF (10% versus 47%, p less than 0.001). The presence of LMW proteinuria indicates a less favourable outcome and the pattern of proteinuria as assessed by the SDS PAGE appears to be a better prognostic index in IgA nephritis than the SI and the GSI. PMID- 1889155 TI - Immediate reconstruction of the lower extremity--an update. AB - The objective of emergency free-tissue transfer of complex lower extremity injuries is to provide primary coverage of the wound at the time of the first surgical procedure during the first 24 hours after the accident. This is achieved by meticulous debridement of soft tissues and bone in the zone of injury, by fracture stabilization by either external or internal fixation, by assuring good circulation with a direct artery repair or by the use of venous or arterial grafts, and by closure of the soft-tissue defect with a suitable free flap with microvascular anastomoses. Such a repair on an emergency basis requires cooperation between orthopedic and plastic surgeons and organization of a continuous microsurgical service. With these prerequisites fulfilled, emergency treatment of complex lower leg injuries gives predictably better results than delayed primary treatment in terms of lower free flap failure rate, lower infection rate, lower number of operations required to obtain the final result, shorter time of hospitalization, shorter time to bone healing and weightbearing, and lower cost of treatment. Emergency free-tissue transfer is not indicated in life-threatening situations. PMID- 1889156 TI - Microvascular reconstruction of the lower extremity in the elderly. AB - The natural changes of aging increase perioperative medical risk factors in the elderly population. Aggressive preoperative patient evaluation and perioperative monitoring can effectively decrease morbidity and mortality rates to equal those of younger patients. The surgical strategy must take into account the increased incidence of atherosclerosis in the inflow and free-tissue transfer recipient vessels. Lower extremity microvascular reconstruction can be performed safely and successfully in the elderly patient. PMID- 1889157 TI - Foot reconstruction in diabetes mellitus and peripheral vascular insufficiency. AB - The great majority of diabetic patients have diabetic foot symptoms. Significant recent advances in reconstructive surgery, as well as improvements in the management of both diabetes mellitus and peripheral vascular disease, make these patients eligible for plastic and reconstructive surgery. Many diabetic patients who would previously have had below-the-knee amputations are now having their complex foot wounds reconstructed. In addition to the metabolic consequences of the disease and the increased susceptibility to infection and wound healing complications, infrapopliteal arterial occlusive disease, peripheral neuropathy, and hemorrheologic changes are addressed in this article. PMID- 1889158 TI - Prevention of complications and correction of postoperative problems in microsurgery of the lower extremity. AB - Prevention of complications in microsurgery of the lower extremities begins with proper patient selection and patient preparation. Complications are highest in elderly patients who have had multiple trauma, smokers, patients with arterial or venous insufficiency, and those with hypercoagulability. Some patients may be best served by primary amputation. If multiple flaps are required, a higher success rate can be achieved with simultaneous rather than sequential transfers. However, for simultaneous transfers, a higher re-exploration rate must be anticipated. The key to avoiding long-term problems with infection is adequate preparation of the wound. Multiple debridements may be necessary. If early coverage can be obtained in trauma cases, a lower rate of chronic osteomyelitis has been observed. Attention to details in the operating room, such as patient warmth and perfusion, will increase the success rate. Recipient vessels must be out of the "zone of injury" and normal in appearance and pulsatility. It is safer to use normal recipient vessels and vein grafts than to attempt anastomoses to vessels affected by "post-traumatic vascular disease." If thrombosis occurs in the early postoperative period, prompt re-exploration can result in flap salvage, with a high degree of predictability if the cause of the thrombosis can be determined and corrected. PMID- 1889159 TI - Revascularization of the lower extremity with omentum. AB - The use of the omental graft with multiple level arterial anastomoses may prove useful for salvaging the severely ischemic lower limb. Because the long-term results of full free omental grafts may depend on neovascularization of the omentum from the surrounding tissue, the technique described here should be utilized only in those patients who are not suitable candidates for other procedures. PMID- 1889160 TI - Bridging bone gaps with the Ilizarov technique. Biologic principles. AB - For the treatment of bone gaps of less than 4 cm, cancellous autografting remains the treatment of choice. But for gaps exceeding 4 cm, the distraction osteogenesis is a viable option. The following conditions should be satisfied: (1) patient selection; (2) stable fixation; (3) osteotomy by corticotomy; (4) 7- to 14-day latency period before initiating distraction; and (5) a controlled rate and rhythm of distraction of 1 mm per day (0.25 mm, four times a day). This type of treatment leaves the pathologic focus alone, and bone healing occurs on the healthy bone. The quality of bone regenerate may be improved by a motorized unit and by better soft-tissue coverage using early grafts and flaps. Interface healing is probably improved by cancellous grafting and internal fixation after the transport period, thus decreasing the fixator time. PMID- 1889161 TI - Management of extremity injuries with external fixator or Ilizarov devices. Cooperative effort between orthopedic and plastic surgeons. AB - Major advances in the last decade have improved the treatment and outcome of patients with moderate to severe lower extremity injuries. Better transport and emergency room facilities, which allow more prompt repair of injuries, advances in bone stabilization, and better methods of soft-tissue reconstruction have led to a significant decrease in amputation and infection rates. This article presents the Mangled Extremity Severity Score (MESS) index and Gustilo's classification to evaluate injuries. Orthopedic, plastic, and vascular surgeons collaborate to manage these injuries in five categories: limb viability, timing, debridement, fixation, and secondary reconstruction. Finally, two cases are presented to demonstrate practical application of these steps, and guiding principles are outlined. PMID- 1889162 TI - Update on chronic osteomyelitis. AB - Recent advances in the understanding of the pathophysiology and treatment of osteomyelitis have been discussed. Some of the advances (in either knowledge or technology) that we have found particularly useful include the following: The discovery of additional prognostic factors, which allow more reliable preoperative assessment. The development of the Ilizarov device, which allows bone fixation and later limb lengthening. Confirmation of the effectiveness of single-staged debridement and muscle flap closure. Confirmation that a brief (10 to 14 day) course of antibiotics is as effective as more prolonged therapy. The development of several new free muscle donor sites and a greater appreciation of the need for careful insetting of the muscle. The development of local antibiotic delivery systems, especially continuous antibiotic irrigation catheters. The development of newer oral and intravenous antibiotics that allow outpatient therapy following surgery. The recognition that patients require extended follow up, and that any recurrences can be successfully treated with a second debridement and muscle flap closure. PMID- 1889163 TI - Judgment and approach for management of severe lower extremity injuries. AB - Severe lower extremity injuries are devastating in their impact on the patient, his or her family, and the future. A critical evaluation of the results of previous salvage efforts provides the basis for the formulation of a treatment strategy. Success can be measured only in terms of functional outcome. The type of therapy is perhaps less important than the effectiveness of establishing a coordinated multidisciplinary approach to these injuries. PMID- 1889164 TI - Muscle flap coverage for the lower extremity. AB - The use of local transposition muscle flaps for coverage of the lower extremity has been overshadowed in recent years by the development of microsurgical techniques for tissue transfer. There are still definite indications for local muscle flaps in reconstruction of the lower extremity. An outline of criteria of selectivity as it applies to specific wounds and practical pitfalls of their use is presented. PMID- 1889165 TI - Blood supply of the lower extremity. AB - The blood supply to the lower extremity has been reviewed, and the concept of direct arterial or axial supply at the groin, fasciocutaneous perforators, and septocutaneous blood vessels in the lower leg has been outlined. The major myocutaneous and fasciocutaneous units in the lower extremity have been outlined and their applications described. All of the reconstructive flaps available are based on a clear understanding of the underlying blood supply. We have tried to look toward what might be multiple contributions of blood supply that may change flap design in an anatomic territory or alter the flap concept entirely. An example would be a myocutaneous flap and its overlying fasciocutaneous territory, or a flap based on a septocutaneous perforator. The plastic surgeon has truly benefited from more in-depth study of the lower extremity blood supply. PMID- 1889166 TI - Analysis of cutaneous perfusion: an aid to lower extremity reconstruction. AB - The use of cutaneous and musculocutaneous flaps has been greatly enhanced by a better understanding of vascular anatomy. Cutaneous vessels reach the skin by three basic pathways: over the muscle layer, through the muscles, and between the muscles. The authors' anatomic investigation of each of these three types of vessels and the clinical application of this information is presented. PMID- 1889167 TI - Fasciocutaneous flaps in reconstruction of the lower extremity. AB - The fasciocutaneous flap, when correctly chosen, can supply an expedient solution for some of the challenging soft-tissue problems in the leg. The fasciocutaneous flap should be included in the list of reconstructive options for the lower extremity, particularly in the distal tibia. The improved knowledge of blood supply to the fasciocutaneous flaps allows the design of a safer, longer, more useful flap. PMID- 1889168 TI - Salvage of prosthetic grafts and joints in the lower extremity. AB - Infection or exposure of prosthetic joints and vascular conduits continues to challenge the reconstructive surgeon. Techniques of regional muscle flaps, fasciocutaneous flaps, and free microvascular transfers have added much to the management of this problem, often converting a hopeless situation to a salvageable one. Close cooperation between the plastic, vascular, and orthopedic surgeons optimizes the chance for a satisfactory outcome. PMID- 1889169 TI - Soft-tissue expansion in lower extremity reconstruction. AB - Soft-tissue expansion in the lower extremities is typically well tolerated. The more proximal one is--that is, the closer to the thigh and buttocks--the easier and less complication prone the expansion will be. It is another valuable technique for resurfacing the lower extremity and for reconstructing defects in contour and in skin character. There are limitations to this technique, which generally is most useful in late reconstructions. Intraoperative expansion has no place in lower extremity reconstruction. Soft-tissue expansion may be limited by an unsuitable geometry or the sheer size of defects. It should not be used next to open wounds. Soft-tissue expansion offers significant advantage in that the coverage of a defect will be replaced with tissue like that lost. Seldom does one see necrosis of advanced flaps, so that there is little risk of tissue loss in using this modality. There is an excellent vascularity to the flaps and an excellent character to the skin. In addition, in this cost-conscious era, soft tissue expansion is quite cost effective, and in many cases the procedures can be conducted on an outpatient basis with a minimum of hospitalization, if any. With care to select patients properly, design carefully, and conduct expansion in a leisurely fashion, soft-tissue expansion offers a valuable means of reconstructing both large and small lower extremity defects. PMID- 1889170 TI - Calf augmentation and correction of contour deformities. AB - In general, augmentation of soft tissue has been a problem for plastic surgeons because of the body's protective mechanisms against foreign material, but silicone rubber implants are the author's choice of the materials currently available. The aesthetic considerations of the shape of the calf and techniques and complications are discussed. This article is generously illustrated with case examples. PMID- 1889171 TI - Resurfacing and sensory recovery of the sole. AB - (1) There is very little quantitative objective information on sensory recovery after resurfacing of the sole. However, based on results obtained by quantitative rather than qualitative methods to measure sensibility, there is little reason to expect a high level of sensory recovery, at least in free flaps. There is no evidence to prove or refute that by using neurosensory flaps or other forms of neurotization, a higher level of sensibility can be achieved, and therefore no reason why such a flap should be specifically selected when reconstructing the sole. Also, the sensibility of the flap has not been shown to be related to the soft-tissue stability after resurfacing of traumatic defects. (2) There are no firm guidelines to flap selection. If possible, a local flap should be selected. If a free-tissue transfer is necessary, a safe choice is for the surgeon to select a familiar flap with a long pedicle of sufficient caliber. The flap should be well tailored into the defect, and excessively thick flaps should be avoided. If in doubt, the donor area can be measured with ultrasonography and compared with the depth of the defect. Muscle flaps should be used to cover deep, irregular, or infected defects, whereas skin flaps are suitable for resurfacing superficial degloving tissue loss. (3) The most important reason for recurrent breakdowns after reconstruction may be abnormally high pressure points in the sole. Bony deformities should be identified preoperatively and removed during the operation. Patient education in meticulous foot care and custom-made insoles or footwear should be provided to prevent reulcerations. (4) The ideal method of resurfacing of the sole would also provide normal sensibility to the skin. With free-flap transfer this cannot be achieved with current techniques. Before new methods of neural reconstruction can be recommended for general use, their efficacy in improving sensibility should be documented by prospective studies using quantitative methods of measurement. If a reduction of breakdowns is claimed, biomechanical studies should be employed to exclude this being merely due to elimination of abnormal pressure points in the sole. PMID- 1889172 TI - Latex agglutination detection of group-B streptococcal inoculum in urine. AB - It is not uncommon for a newborn to be blood culture negative, but urine latex particle agglutination (LPA) positive for group-B streptococcus (GBS). We hypothesized that whole-cell GBS contamination of urine, which is possible in bag collected specimens, could cause LPA positivity. Serial tenfold dilutions through 10(-8) of an 18-hr broth suspension of GBS serotype III were prepared in sterile urine. Directigen (Becton-Dickenson Microbiologic Systems, Cockeyville, MD) LPA testing was performed on each sample at inoculation and, if negative, every 2 hr until becoming LPA positive. All tubes were quantitiatively cultured when becoming LPA positive. The assay was performed four times to evaluate independently the effects of urine sample centrifugation, volume, glucose content, and incubation temperature. An 18-hr GBS suspension dilution of 1:10,000 in urine and as few as 5.7 x 10(3) organisms/ml caused LPA positivity at time 0. Urine supported sufficient replication to enable log 0 concentrations (10(-8) dilution) to become LPA positive within 8 hr at 35 degrees C, a routine infant incubator setting. Alteration by centrifugation, volume, or glucose content had no effect on LPA positivity or time needed to become positive. We conclude that Directigen LPA can detect a relatively small concentration of GBS organisms in urine. Due to potential contamination from skin bacteria, positive LPA results from bag urine should be interpreted with caution in the absence of positive cultures. PMID- 1889173 TI - The clinical microbiology laboratory as an aid in infection control. The application of molecular techniques in epidemiologic studies of methicillin resistant Staphylococcus aureus. AB - A microbiologic surveillance study was performed in order to estimate the point prevalence, source, and nosocomial acquisition of methicillin-resistant Staphylococcus aureus (MRSA) within the Iowa City Veterans Affairs Medical Center (IC VAMC). Immediately following the microbiologic surveillance study, a cluster of nosocomial MRSA infections was detected by routine infection control surveillance. An epidemiologic investigation was conducted and all isolates of MRSA detected during the microbiologic surveillance study and the subsequent cluster of nosocomial infections were characterized by restriction endonuclease analysis of plasmid DNA (REAP). REAP subtyping defined a total of ten distinct subtypes from 24 patients infected or colonized with MRSA. The documentation of a single subtype of MRSA (subtype A2) in nine patients from the surgical service, eight of which were hospitalized in the surgical intensive care unit, provided convincing evidence of a breakdown of infection control practices in that unit. REAP subtyping was a highly discriminating means of identifying different subtypes among the various isolates of MRSA and was useful in directing infection control efforts to specific problem areas within the hospital. Molecular typing methods, such as REAP, when used appropriately in conjunction with careful epidemiologic investigation provide an effective approach to the investigation and control of the spread of MRSA within the hospital. PMID- 1889174 TI - Laboratory diagnosed human viral infections in Canada, 1980-1988. Trends and clinico-epidemiological characteristics. AB - Between 1980 and 1988, the Laboratory Centre for Disease Control (LCDC) received 261,573 reports of positive laboratory diagnoses of viral and selected nonviral agents from Canadian laboratories for the determination of the distribution of these agents with age, seasonality, periodicity, and symptoms. The agents most frequently associated with diseases of the respiratory and gastrointestinal tracts, skin, and mucous membranes, the eye, and the central nervous system are identified and ranked. The temporal patterns of common enteroviruses and vaccine preventable diseases are also described. New diagnostic techniques, availability of diagnostic services, awareness of the role an agent plays in disease, and real changes in the occurrence of a disease may influence the number of positive laboratory reports. PMID- 1889175 TI - Correlation of the percent of positive Chlamydia trachomatis direct fluorescent antibody detection tests with the adequacy of specimen collection. AB - Chlamydia trachomatis is an obligate, intracellular parasite infecting the columnar and transitional cells lining the endocervix, uterus, fallopian tubes, rectum, urethra, and epididymis. We determined if the percent of specimens positive for C. trachomatis in the Microtrak Direct Specimen Test depended on the quality of specimens obtained. Female genital slides (649) were evaluated by the direct fluorescent antibody (DFA) test for the presence and numbers of (a) C. trachomatis elementary bodies and (b) columnar, transitional and squamous epithelial cells, and polymorphonuclear neutrophils (PMNs). Only 138 (21.3%) of the 649 slides were considered to be adequately taken, that is, containing columnar/transitional cells either alone or in conjunction with squamous cells and/or PMNs. Of the 138 adequate slides, 10 (7.2%) were C. trachomatis positive. However, 511 (78.7%) of the 649 slides were judged inadequate; 395 contained only squamous cells and/or PMNs, 19 were too thick to determine cell types, 46 contained only cell debris, and 51 contained neither cells nor debris. Only four (0.78%) of 511 were C. trachomatis positive. Thus adequate specimens containing columnar/transitional cells for C. trachomatis detection had a tenfold increase in the percent of positive results compared to inadequately collected specimens. By using the DFA test, one has the advantage of determining the adequacy of the specimens obtained as well as the presence of chlamydiae. PMID- 1889176 TI - Antibiotic susceptibility profile of Xanthomonas maltophilia. In vitro activity of beta-lactam/beta-lactamase inhibitor combinations. AB - The susceptibility of 42 strains of Xanthomonas (Pseudomonas) maltophilia to 37 antibiotics (mainly beta-lactams, aminoglycosides, and fluorinated quinolones) was tested. Xanthomonas maltophilia was resistant to most beta-lactams, with ceftazidime, moxalactam, and ICI-194008 being the most active ones. Aminoglycosides had a very modest activity, with quinolones showing only moderate activity against this species. Trimethoprim/sufamethoxazole was effective against all strains tested. We also tested the synergy of several beta-lactam/beta lactamase inhibitors against X. maltophilia. Only aztreonam/clavulanic acid at 3:1, 1:1 and, mainly, 2:1 combinations had synergistic activity, decreasing the rate of resistance from 92.8% for aztreonam alone to 32.4% for aztreonam clavulanic acid at 1:1 and 0% for aztreonam-clavulanic acid at 2:1. PMID- 1889177 TI - In vitro antibacterial activities of the fluoroquinolones PD 117596, PD 124816, and PD 127391. AB - Three new aminopyrrolidine-substituted fluorocyclopropyl quinolones--PD 117596, PD 124816, and PD 127391--were tested for in vitro antibacterial activity against 349 bacterial strains, which are primarily clinical isolates. The minimum inhibitory concentrations (MIC) in micrograms/ml required for greater than or equal to 90% of strains were 0.03-0.06 for staphylococci (26 strains); 0.06-0.25 for Streptococcus pyogenes, S. agalactiae, S. pneumoniae, and Enterococcus faecalis (80); less than or equal to 0.015 for Branhamella catarrhalis, Haemophilus influenzae, and Neisseria gonorrhoeae (42); 0.06 for Enterobacteriaceae (97); 0.125-0.25 for Acinetobacter spp. (14); 0.5 for Pseudomonas aeruginosa (20); 0.125-1.0 for Bacteroides fragilis (13); and 0.25 0.5 for anaerobic cocci (11). These activities were generally superior to that of ciprofloxacin, imipenem, ampicillin, penicillin G, oxacillin, cefazolin, ceftazidime, cefoxitin, cefsulodin, aztreonam, piperacillin, amikacin, spectinomycin, doxycycline, erythomycin, clindamycin, metronidazole, and vancomycin. The activities of the new quinolones were generally unchanged with light, 50% human serum, aerobic/anaerobic atmosphere, 5% sodium choate, cation supplementation, and 100-fold increased or decreased inoculum; as with other quinolones, potency was measurably diminished with decreasing pH (pH less than or equal to 6.0) and in 100% urine. PMID- 1889178 TI - Comparison of agar versus broth dilution techniques for determining antibiotic susceptibilities of Ureaplasma urealyticum. AB - We determined minimal inhibitory concentrations (MIC) for tetracycline and erythromycin for 72 clinical isolates using broth and agar dilution methods. Erythromycin MIC ranges were less than 0.125-8 micrograms/ml and 1-64 micrograms/ml in broth and agar, respectively. The erythromycin MIC50 and MIC90 as determined by broth were two dilutions (fourfold) lower than those for agar. Tetracycline MIC ranges in broth and agar were less than 0.125-greater than 64 and 0.25-greater than 64 micrograms/ml, respectively. The tetracycline broth MIC50 was one dilution lower than that for agar. The tetracycline broth MIC90 was 64 micrograms/ml and that for agar was greater than 64 micrograms/ml. Of the strains tested, 98.6% using broth were susceptible or moderately susceptible to erythromycin as compared with 75% using agar, representing a significant difference (p less than 0.001). For tetracycline, 80.6% of strains were susceptible or moderately susceptible using broth and 73.6% using agar. MICs were determined by agar dilution after 72 and 96 hr of incubation in 32 strains. There was an increase in the erythromycin MIC by one dilution in 16 strains and two dilutions in one strain with the longer incubation. The tetracycline MIC increased by one dilution in nine strains between readings. Broth MICs were reproducible with one dilution for both drugs in 10 of 12 strains tested twice. Agar MICs were reproducible within a maximum of two dilutions (fourfold). Different interpretations of susceptibility versus resistance may be made depending on which assay is utilized, thus influencing conclusions regarding spectrum of activity of investigational drugs as well as treatment options. The technique employed should always be considered whenever apparently differing drug susceptibility patterns are reported. PMID- 1889179 TI - Reproducibility of Staphylococcus epidermidis plasmid profiles. AB - The plasmid profiles of six isolates of Staphylococcus epidermidis were repetitively evaluated over an 8-month period. Each isolate was subcultured and stored at three different temperatures (-70 degrees C, -20 degrees C, and room temperature) and plasmid DNA was prepared from each subculture at 0, 1, 4, and 8 months by two different methods of plasmid extraction [using mixed alkyltrimethylammonium bromide (ATAB) or Brij 58 and deoxycholate (modified Parisi)]. Plasmid DNA bands were lost from two isolates when subcultures were kept at room temperature. This plasmid loss was confirmed by repetitive extractions and electrophoresis, as well as by restriction endonuclease analysis of the ATAB preparations. Profiles were otherwise highly related to one another, with occasional exceptions being extra or missing plasmid DNA bands of high molecular size. The latter findings were not reproducible. Plasmid DNA extracted by the modified Parisi method was not reliably digested with restriction endonuclease enzymes. We conclude that the plasmid profiles of Staphylococcus epidermidis isolates are highly reproducible as long as isolates are stored at less than or equal to -20 degrees C. Minor discrepancies in the number of plasmid DNA bands of large molecular size may occur. These are resolvable by repetitive testing or restriction endonuclease analysis of ATAB-extracted plasmid DNA preparations. PMID- 1889180 TI - Evaluation of the modified Visuwell Strep-A enzyme immunoassay for detection of group-A Streptococcus from throat swabs. AB - The modified Visuwell Strep-A enzyme immunoassay (EIA) was compared with culture for detection of group-A Streptococcus from throat swabs. Throat swabs in modified Stuarts medium obtained after culture at two institutions were tested in Visuwell. Cumulative results were n = 417, sensitivity 87.8%, specificity 89.9% predictive value positive (PVP) 67.9%, predictive value negative (PVN) 96.8%, and accuracy 89.5%. At another site, swabs were delivered to the laboratory without transport medium, cultured, and subsequently tested by Visuwell (n = 202, sensitivity 79.6%, specificity 84.5%, PVP 65.2%, PVN 91.9%, accuracy 83.2%). When 1+ culture-positive specimens were considered negative, the sensitivity and PVN increased from 79.6% to 90.2% and 91.9% to 97.1% respectively. Overall performance of the modified Visuwell was comparable with that of the initial assay for throat swabs transported with or without modified Stuarts medium. Cross reaction with organisms other than group-A Streptococcus normally found in the oropharynx was negligible in Visuwell and the limit of detection of group-A Streptococcus was 5 x 10(4) colony-forming units. PMID- 1889181 TI - Antimicrobial activity of E-1040, a novel thiadiazolyl cephalosporin compared with other parenteral cephems. AB - E-1040, a new parenteral fourth-generation cephalosporin, was tested against greater than 600 bacteremic pathogens and compared with cefotaxime, ceftazidime, and cefpirome. E-1040 activity against Staphylococcus aureus was comparable (MIC90, 8 micrograms/ml) to ceftazidime, but inferior to cefotaxime (MIC90, 2 micrograms/ml) and cefpirome (MIC90, 0.5 microgram/ml). beta-Hemolytic streptococci and most Gram-positive anaerobes were also susceptible to E-1040. Some strains of coagulase-negative staphylococci, all oxacillin-resistant Staphylococcus spp., enterococci, and Bacteroides fragilis group strains were resistant to E-1040 (MIC90, greater than 64 micrograms/ml). Comparative tests for E-1040 and the three other cephalosporins against pseudomonads and nonenteric Gram-negative bacilli showed E-1040 to be generally most active. The E-1040 MIC90 for Pseudomonas aeruginosa was 1 microgram/ml and for ceftazidime it was 4 micrograms/ml. Haemophilus influenzae, Moraxella catarrhalis, and Neisseria spp. has E-1040 MIC90s ranging from 0.12 to 2 micrograms/ml. Neisseria gonorrhoeae, strains resistant to penicillin, did not have markedly elevated E-1040 MICs compared with penicillin-susceptible strains. Enterobacteriaceae species had all MICs of less than or equal to 8 micrograms/ml for E-1040 and cefpirome, indicating activity against strains producing stably derepressed beta-lactamases. E-1040 appeared to be beta-lactamase stable, little influenced by testing systems or media, and was bactericidal. E-1040 seems to have promise as a parenteral beta lactam for use on strains resistant to "third-generation" cephalosporins and other families of drugs such as aminoglycosides and fluoroquinolones. PMID- 1889182 TI - Antibacterial activity of rokitamycin compared with that of other macrolides. AB - The activity of rokitamycin, a 16-membered macrolide, was compared with other macrolides and agents used to treat respiratory infections. Rokitamycin had in vitro activity against streptococci and Streptococcus pneumoniae comparable to the other macrolides, inhibiting most organisms at less than 0.03 to 0.5 microgram/ml. It was the most active macrolide agent against Staphylococcus aureus, inhibiting 90% at 1 microgram/ml. Macrolide-resistant streptococci and staphylococci in which resistance was inducible were inhibited, but constitutively resistant Gram-positive bacteria were resistant. Rokitamycin was less active than erythromycin against Haemophilus influenzae, but had activity comparable to erythromycin against Moraxella catarrhalis and Neisseria gonorrhoeae. It inhibited Clostridium spp. and peptostreptococci, but had poor activity against Bacteroides species. Rokitamycin was bactericidal for streptococci and staphylococci, but not for enterococci. Overall rokitamycin has in vitro activity comparable to currently available 14-membered macrolides. Its clinical utility will be influenced by the degree of metabolism to less active metabolites since 70% is rapidly metabolized. PMID- 1889183 TI - In vitro activity of 43 antimicrobial agents tested against ampicillin-resistant enterococci and gram-positive species resistant to vancomycin. AB - A total of 57 strains of ampicillin-resistant and -susceptible enterococci representing 10 species and 23 strains of vancomycin-resistant Gram-positive bacteria (Leuconostoc and Pediococcus) were tested to determine their susceptibility to 43 antimicrobial agents by the reference broth microdilution method. The drug MICs for the ampicillin-resistant enterococci were generally similar to those of ampicillin-susceptible strains, that is, highly resistant to cephalosporins, moderately susceptible or resistant to quinolones, and susceptible to "glycopeptides." Some investigational quinolones (PD127391, sparfloxacin, WIN57273), minocycline, and rifampin were highly active. Vancomycin resistant strains were usually resistant to other "glycopeptides," for which correlation coefficients of MICs ranged from 0.881 to 0.978, except ramoplanin (MICs, 0.008-0.5 micrograms/ml). Most isolates resistant to vancomycin were susceptible to the newer quinolones, penicillins, aminoglycosides, clindamycin, and erythromycin, but highly resistant to cephalosporins. Discrepancies between the MICs and MBCs for glycopeptides were noted (greater than or equal to 8-fold, MBC50/MIC50), but not for ramoplanin. The vancomycin disk test was in 96.1% absolute agreement by identifying resistant strains without contributing false susceptible, very major error. PMID- 1889184 TI - Infections with Rhodococcus equi in children. AB - Three cases of serious infection in children, including the first two reports of bacteremia, due to Rhodococcus equi are described. Only seven pediatric cases have been reported to date. In the laboratory, R. equi can easily be misidentified as a nonpathogenic Corynebacterium spp. (diphtheroid) or a Mycobacterium spp. Despite an overall mortality rate of 25% in adults, no pediatric deaths have occurred due to R. equi. The organism is generally susceptible to vancomycin, aminoglycosides, chloramphenicol, and erythromycin, but, optimal duration of antibiotic therapy is unknown. Treatment with multiple antibiotics was successful in all three cases reported here. Although only a small number of cases have been reported in children, R. equi appears to be an important pediatric pathogen. PMID- 1889185 TI - Simultaneous infection with multiple serotypes of Shigellae in a patient. AB - We isolated three different serotypes of Shigella on admission from a patient with dysentery as well as a Shigella-like organism and Campylobacter jejuni upon follow-up. The patient produced serum antibodies to all three serotypes of shigellae. PMID- 1889186 TI - In vitro activity of sparfloxacin (AT-4140 and CI-978), a new quinolone antimicrobial agent, against Haemophilus and gram-positive cocci. AB - Sparfloxacin (AT-4140 and CI-978) was evaluated for activity against 194 clinical isolates of staphylococci, streptococci, Enterococcus faecalis, anaerobic Gram positive cocci, and Haemophilus sp. The MIC of sparfloxacin for greater than 93% of the strains tested was less than or equal to 0.5 microgram/ml. Sparfloxacin demonstrated increased activity against enterococci, staphylococci, pneumococci, and anaerobic cocci when compared with ciprofloxacin. PMID- 1889187 TI - Antimicrobial activity of cefpirome. An update compared to five third-generation cephalosporins against nearly 6000 recent clinical isolates from five medical centers. AB - Cefpirome, cefotaxime, ceftazidime, cefoperazone, ceftizoxime, and ceftriaxone were tested against approximately 6000 fresh clinical isolates from five medical centers. For 3031 strains of Enterobacteriaceae tested, cefpirome consistently had the lowest MIC50s and lowest percentage of resistant strains. Cefpirome was also the most active agent against the 2138 Gram-positive cocci tested; Staphylococcus haemolyticus was uniformly resistant to all agents tested. Against 791 nonenteric Gram-negative bacilli, the activity of cefpirome was most comparable to that of cefoperazone and slightly less active than ceftazidime. Among the current third-generation cephalosporins, cefotaxime and cefoperazone emerged as having better overall balanced activity. Ceftazidime displayed poorest coverage against Enterobacteriaceae and Gram-positive organisms. Ceftizoxime also provided compromised coverage of staphylococci and nonenteric Gram-negative bacilli. Cefpirome remains as active as originally described in 1984 and possesses a slightly wider spectrum of activity against contemporary aerobic pathogens compared to currently marketed third-generation cephalosporins. PMID- 1889188 TI - Randomization analysis of dental data characterized by skew and variance heterogeneity. AB - Many distributions of dental variables exhibit positive skew and variance heterogeneity. Although the use of parametric tests on data with these disturbances usually does not pose a problem with respect to alpha error level, transformation of data sometimes increases power. Occasionally one or both of these expectations do not hold and it becomes problematic as to whether data should be transformed and which analyses should be considered valid. Simulated dental trials were conducted on independent samples (n = 25 per group) drawn from exponential distributions with the same or different population means, t-tests on raw, log, and square root transformed data; the Mann-Whitney-Wilcoxon ranking test; and a randomization test, all exhibited satisfactory levels of alpha error but the randomization test exhibited the greatest power followed closely by the t test on raw scores. The present results demonstrate that the log transformation does not increase power for all forms of positively skewed data. Randomization tests, not being subject to normality and variance homogeneity assumptions, may yield greater confidence in validity in these cases. Some implications for analytical strategy are discussed. PMID- 1889189 TI - Effect of time costs on demand for dental services among adults in Norway in 1975 and 1985. AB - The aim of the present study was to assess the effect of travel time, time spent on a waiting list and time spent in the waiting room on demand for dental services in Norway. The analysis was performed on two sets of national data from 1975 and 1985, and on one set of local data from 1987. The national data were representative of the non-institutionalized Norwegian population aged 20 yr and above. Travel time had an effect on demand in 1975, but not in 1985. Time spent on a waiting list had no opportunity cost, and did not influence demand. There was a statistically significant association between time spent in the waiting room and demand. However, this association disappeared when the effect of dental attendance pattern was controlled for. Regular attenders had shorter waiting times than those who were irregular attenders. This study has shown that factors such as presence of teeth, family income, and age are more important than travel time on demand for dental services. PMID- 1889190 TI - Cohort comparisons of dental status in the adult Swedish population between 1975 and 1981. AB - The aim was to describe and analyze changes in dental status in Sweden over a 6 yr period, and to establish a baseline for a subsequent investigation. Representative samples of the Swedish population in 1975, 1977, and 1981 were investigated by means of interviews. The participation rate varied between 81 and 86% and the number of participants between 11,582 and 14,964. Dental status, based on a question about natural teeth and/or removable denture(s), was analyzed in relation to demographic, socio-economic, social support and life style factors. The prevalence of edentulism in the age group 16-74 years decreased during the observation period from 12.7% to 9.9% in men and from 15.5% to 11.2 in women. Besides age, urbanization, occupation and tobacco smoking had the highest explanatory value for edentulism. The findings are discussed with respect to the increasing life expectancy and possible changes in the need and demand for dental care. PMID- 1889191 TI - Tooth loss and dental caries in Dutch adults. AB - As part of a nationwide dental survey in 1986 a caries study was executed in 3526 adults, aged 15-74 yr, living in 40 residential areas in The Netherlands. Marked differences were found between the social classes distinguished (more edentates in the lower classes) and between the different regions. It is supposed that these differences reflect the lack of dental manpower in the past. PMID- 1889192 TI - Effects of diagnostic threshold and overlapped approximal surfaces on reported caries status. AB - The aims of this study were to examine the influence upon reported caries status of: 1) employing different diagnostic thresholds and 2) using differing conventions for treating approximal surfaces which appeared overlapped on posterior bitewing radiographs. Caries prevalence data from a group of 211 Scottish schoolchildren aged 5-15 yr studied during a trial of elective temporary tooth separation in general dental practice in Scotland were used. In this "moderate" caries group, values for dmft/DMFT rose significantly (P less than 0.001) when the D1 diagnostic threshold (all grades of lesion accepted) was applied in comparison with the D3 threshold (only caries into dentine recognised); dmft increasing from 3.9 to 5.4 and DMFT increasing from 1.7 to 4.7. This demonstrated that an over-optimistic impression of overall caries levels may be given when only the D3 threshold is used uncritically. In this study the status of approximal surfaces which were overlapped on bitewing radiographs was assessed by direct clinical examination using the temporary elective tooth separation technique. The investigation showed that, for this juvenile population, most (81.8% mesial, 93.1% distal) overlapped approximal surfaces were sound. Significantly more mesial than distal surfaces were found to be overlapped. PMID- 1889193 TI - Comparison of patients' views and dentists' evaluations 5 years after complete denture treatment. AB - This study describes a comparison of patients' views of their dentures and dentists' technical evaluations 5 yr after complete denture treatment. Of the original sample (n = 139) a test group of 92 patients remained available for the actual study 5 yr after treatment. Firstly, the patients filled in a questionnaire regarding their complaints of and (dis)satisfaction with dentures. Secondly, they were examined independently by two experienced dentists in order to evaluate their dentures. Finally, after considering the answers to the questions in the questionnaire and their own dentures' evaluation the dentists proposed a therapy. It was found that patients and dentists agree on assessments of denture retention, but do not agree on assessment of denture aesthetical aspects. Furthermore, it appeared that generally more therapy was rendered by the dentists than could be expected on the basis of their evaluations and the patients' views. PMID- 1889194 TI - Finnish dentists as tobacco counselors. AB - The first nationwide survey of Finnish dentists' use of tobacco, their inquiring about and advising patients on tobacco use, and their attitudes toward anti tobacco health education (ATHE) was carried out at the end of 1987. A questionnaire mailed to 540 dentists produced 435 answers (81%). One fourth of the male dentists and 6% of the female dentists currently were smokers, and 11% of men and 2% of women smoked daily. Information on smoking practices of patients was obtained always by 8%, often by 18%, and occasionally by 62% of the dentists. Four percent of the dentists advised always and 15% often their patients about smoking, and 62% did so occasionally. The majority of the dentists agreed that dentists should take part in ATHE and that dentists can encourage patients to stop using tobacco. The respondents supporting the involvement of dentists in ATHE reported having an active role in tobacco counseling (TC) significantly more frequently than those not sharing the idea of involvement. It was concluded that Finnish dentists could be a valuable resource in TC because of their positive attitudes. PMID- 1889195 TI - Tooth loss and caries prevalence in older Floridians attending senior activity centers. AB - Older adults attending 14 senior activity centers in six countries of Florida cooperated for a questionnaire and an oral examination. The mean age was 76.5 yr, and about one-third were 80 yr or older. One-third of the dentate persons had dental caries. Most of the carious lesions were on the crown, not the root, and most of the decay was primary, not recurrent. Most of the persons with a need for caries treatment were likely to seek dental care; however, the majority of carious surfaces were in persons who reported being infrequent users of care. These results from ambulatory older adults suggest that older adults have significant caries treatment needs, and provide support for the view that the treatment of older U.S. adults may grow in the coming decades. PMID- 1889196 TI - A study to determine oral health needs of institutionalised elderly patients by non dental health care workers. AB - In this survey normative need as assessed by an examining dentist and the subject's own perceived need are compared with need assessed by untrained care workers. A method for simple assessment of elderly people on admission to day centres or elderly peoples' residential homes is described and its efficiency in use assessed during a survey of 41 subjects. Results suggest that use of a simple questionnaire can alert carers to problems requiring dental care--oral hygiene regimens can then be improved, dentures named and dentists called to provide treatment. Too often this type of initial assessment is neglected. PMID- 1889197 TI - Dental caries of 12- and 15-year-old schoolchildren in Gazankulu, South Africa. PMID- 1889198 TI - Prevalence of dental decay and treatment needs in Algerian schoolchildren and adolescents in the Constantine area. PMID- 1889199 TI - A model for diagnosing and explaining multiple disorders. AB - The ability to diagnose multiple interacting disorders and explain them in a coherent causal framework has only partially been achieved in medical expert systems. This paper proposes a causal model for diagnosing and explaining multiple disorders whose key elements are: physician-directed hypotheses generation, object-oriented knowledge representation, and novel explanation heuristics. The heuristics modify and link the explanations to make the physician aware of diagnostic complexities. A computer program incorporating the model currently is in use for diagnosing peripheral nerve and muscle disorders. The program successfully diagnoses and explains interactions between diseases in terms of underlying pathophysiologic concepts. The model offers a new architecture for medical domains where reasoning from first principles is difficult but explanation of disease interactions is crucial for the system's operation. PMID- 1889200 TI - Alveolar sacs and the expirograms of He and SF6: a model study. AB - In 1975, Hansen and Ampaya described alveolated outpouchings in the walls of the acinar ducts, which were observed in all airway generations within the acini. These structures were called alveolar sacs, and they appear to contain the larger fraction (56%) of the acinar volume. The total depth of an alveolar sac including its alveoli (approximately 0.32 mm) is comparable to the mean length of an acinar duct (0.18 to 0.97 mm). Therefore, the alveolar sacs contribute to the asymmetric morphology of the acini. In this paper we investigate the impact of this aspect of the alveolar sacs on the shape of the expirograms of He and SF6. To that end, single-breath washout experiments were simulated with two different mathematical lung models. The one model is an airway model in which the alveolar sacs are modelled explicitly by separate compartments. The expirograms obtained with this model are compared to those obtained with a conventional axisymmetric airway model which is used as a reference model. In this model the volumes of the alveolar sacs are added to those of the acinar ducts; i.e., both air spaces are represented by the same compartments. The washout of He and SF6 was simulated for three different breathing maneuvers corresponding to ventilatory conditions at rest and at exercise. Comparison of the expirograms obtained with the two models showed no differences between their shapes when identical dimensions are used for the lengths and cross sections of the alveolar ducts in the two models. We conclude that the contribution of the alveolar sacs to the asymmetric morphologic structure of the acini has no consequences for the shape of the expirograms of He and SF6. PMID- 1889201 TI - On two weighted signal averaging methods and their application to the surface detection of cardiac micropotentials. AB - In this paper, the variance normalized averaging (VNA) and the optimal weighted averaging (OWA) are derived and their application to the surface detection of cardiac micropotentials is discussed. Theoretical analysis and computer simulation showed that VNA and OWA are superior to the conventional signal averaging (CSA) in reducing random noise with changing variance and the larger the change of noise variance the better the improvements of VNA and OWA relative to CSA. Clinical application of VNA and OWA using a proposed noise variance estimation technique indicated that residual noise on the PR and ST segments can be further reduced in most of the cases. This manifests that the new techniques have a potential advantage for improving the effectiveness of signal averaging as a fundamental method for surface detection of cardiac micropotentials. PMID- 1889202 TI - A model for critiquing based on automated medical records. AB - We describe the design of a critiquing system, HyperCritic, that relies on automated medical records for its data input. The purpose of the system is to advise general practitioners who are treating patients who have hypertension. HyperCritic has access to the data stored in a primary-care information system that supports a fully automated medical record. Hyper-Critic relies on data in the automated medical record to critique the management of hypertensive patients, avoiding a consultation-style interaction with the user. The first step in the critiquing process involves the interpretation of the medical record in an attempt to discover the physician's actions and decisions. After detecting the relevant events in the medical record, HyperCritic views the task of critiquing as the assignment of critiquing statements to these patient-specific events. Critiquing statements are defined as recommendations involving one or more suggestions for possible modifications in the actions of the physician. The core of the model underlying HyperCritic is that the process of generating the critiquing statements is viewed as the application of a limited set of abstract critiquing tasks. We distinguish four categories of critiquing tasks: preparation tasks, selection tasks, monitoring tasks, and responding tasks. The execution of these critiquing tasks requires specific medical factual knowledge. This factual knowledge is separated from the critiquing tasks and is stored in a medical fact base. The principal advantage demonstrated by HyperCritic is the adaption of a domain-independent critiquing structure. We show how this domain-independent critiquing structure can be used to facilitate knowledge acquisition and maintenance of the system. PMID- 1889203 TI - An interlingua for electronic interchange of medical information: using frames to map between clinical vocabularies. AB - The proliferation of medical knowledge has led to the development of extensive dictionaries for electronically accessing information resources. The task of standardizing terminology used for electronic hospital records and for knowledge bases for medical expert systems and indexing the medical literature cannot easily be met by developing a single, monolithic "official" medical vocabulary. Developing a monolithic vocabulary would require a massive effort, and its existence would not guarantee its use by third-party payors, by practicing clinicians, or by developers of electronic medical information systems. Recognizing this, the National Library of Medicine (NLM) has begun to develop the Unified Medical Language System (UMLS) as a means of promoting electronic information exchange among systems with controlled vocabularies. The authors describe a frame-based system developed as an experimental approach to mapping between controlled clinical vocabularies. PMID- 1889204 TI - Ten years' experience in a cardiovascular disease prevention community programme in Austria. AB - In 1977, a field survey of coronary risk factors was undertaken in a Tyrolean village. All inhabitants aged between 20 and 64 years were investigated for hypercholesterolaemia, hypertension and smoking. In subsequent years a community intervention programme was developed and implemented in a joint endeavour between the general practitioners of the village and the project leader. After 10 years, in May 1987, a new survey was conducted in the age group 20 to 74 years. The mean values for systolic and diastolic blood pressure as well as the plasma cholesterol level in the population were found to be significantly lower than 10 years previously. There was a substantial, but not significant reduction in the percentage of male smokers in the age group 20 to 64 years, but no change in the percentage of female smokers. PMID- 1889205 TI - Modification of cardiovascular risk factors in rural population of Newfoundland through nutritional counselling. AB - Cardiovascular risk factor (CVRF) evaluation has been offered to the adult population of a rural area of Newfoundland. Out of 4,814 residents of the selected communities 522 persons volunteered for a screening examination. The assessed variables included medical history, blood pressure, total cholesterol, smoking and body mass index. The most frequent CVRF encountered had been hypercholesterolaemia, ascertained in 61% of all residents. Among the respondents 30% were smokers and 27% were hypertensives. A six-month intensive educational programme aimed at a cohort of 41 high risk individuals led to a significant decline of systolic blood pressure, body mass index and serum cholesterol. Although, after termination of the intervention programme six months later, the risk factor levels increased again, they have remained below the original values. The results of this pilot study led to a design of a major random clinical trial on non-pharmacological therapy to be implemented in the years 1990/1993. PMID- 1889206 TI - Cardiovascular risk factors in the Czech population. AB - In 1985 and 1988 as part of the WHO's MONICA project two surveys of cardiovascular risk factors were conducted in the population aged 25 to 64 years and resident in the six districts of the Czech Republic collaborating in MONICA. Over a period of three years, the prevalence of smoking decreased from 46% to 41.8% (p less than 0.05) in men. Daily cigarette consumption declined from 17.9 to 15.1 (p less than 0.001) in men and from 11.1 to 10.1 (p less than 0.05) in women. Despite the unchanged prevalence of hypertension during the three years' period the proportion of population with elevated BP levels declined from 22.25% to 19.1% in men (p less than 0.05), and from 16.8% to 14.0% (p less than 0.05) in women as a result of better hypertension control. The prevalence of obesity in men rose from 18.5% to 23.9% (p less than 0.001). The proportion of individuals with a total cholesterol level over 5.2 mmol/l rose from 78.0% to 83.1% (p less than 0.001) in men and from 75.9% to 80.6% in women (p less than 0.01). The changes were favourable only in those risk factors that were actively influenced by the preventive programmes "A Chance for Three Million" in smoking habits, and the "National Programme of Hypertension Control". The authors believe that consistent nationwide preventive programmes might exert a beneficial effect on the profile of risk factors of the whole Czech population. PMID- 1889207 TI - Non-pharmacological control of blood pressure and physical fitness in subjects with arterial hypertension. AB - In a group of 60 men and 17 women aged 54 +/- 9 yrs. suffering from mild and moderate arterial hypertension (i.e. 90 greater than DBP less than 120 mmHg), a five-week non-pharmacological intervention programme in spa led to a reduction in body weight by 5 kg, an increase in maximum tolerated workload by 4 W, a decrease in blood pressure at rest by 12/6 mmHg on average, and a decrease in heart rate during exercise and in the recovery phase. The training effect persisted in a certain degree for a long time (i.e. 14 months on average after spa treatment). The reduction in weight, heart rate and systolic blood pressure at rest persisted as well. The therapy resulted in a decrease in minute ventilation and there was no increase in aerobic capacity. No change in the number of pathological ECG changes at rest and during exercise was observed during spa treatment. The regimen and training measures enable to reduce pharmacological therapy in 60% of originally treated hypertensives. This kind of spa treatment constitutes a model of a rational lifestyle for persons with arterial hypertension. PMID- 1889208 TI - Serum cholesterol increase in a middle-aged male industrial population during ten years (1976-1986) and general food consumption changes in Czechoslovakia. AB - The authors evaluate the coronary risk factor changes in middle-aged men from the point of view of changed nutritional habits of the whole population (yearly per capita consumption of different food). They compared 3,754 men aged 40-50 years when screened in 1976-77 (Skoda I Study) and 568 men aged 40-50 years when screened in 1986-88 (Skoda II Study). During the 10-year period, a significant decrease of smoking habits was observed, hypertension prevalence remained unchanged and hypercholesterolaemia prevalence increased significantly. The estimated yearly per capita consumption of meat and fat remained unchanged in the years 1975-1985, however, the structure of consumption revealed a gradual change towards food containing high amounts of animal fat. Education efforts during the 10-year period (1976-1986) led to a decrease in smoking habits in middle-aged men leaving hypertension control unchanged. The observed increase of cholesterol levels may be attributed to inappropriate nutritional habits gradually worsening in the whole population probably due to a socio-economic depression. PMID- 1889209 TI - Cholesterolaemia in school-age children and hypercholesterolaemia aggregation in the family. AB - The distribution of cholesterol values was established in a group of 2,000 Prague children aged 11-12 years. Of these, 100 children with cholesterol values exceeding the 95th percentile (HYPER), and 100 children with values between the 5th and the 10th percentiles (HYPO) were selected for follow-up. In addition to a thorough clinical and laboratory examination in children and parents, three-day food consumption was registered in children. Even though differing significantly from those assigned to the HYPO group in lipid spectrum parameters, HYPER group children did not show any abnormalities in carbohydrate metabolism or increased incidence of obesity. There is no significant difference in the energy values of food consumed by HYPER and HYPO children. Although a significantly higher proportion (in per cent) of total lipids and animal fat consumption was found in HYPER boys (p less than 0.05), the proportions (in per cent) of fatty acids, and the unsaturated/saturated fatty acid ratio in HYPER and HYPO children did no differ significantly. Parents of HYPER children showed significantly higher mean values of cholesterol, apolipoprotein B, LDL cholesterol and more unfavourable atherogenic index values. Hypercholesterolaemia aggregation in both parents was likewise significantly higher in children assigned to the HYPER group. PMID- 1889210 TI - Blood thiocyanate levels and self-reported smoking habits compared in two large cardiovascular population studies. AB - In two representative population surveys (n1 = 1712, n2 = 3757, age-range: 25-64 years) from six towns in Northern Badenia (FRG) self-reported smoking habits and blood thiocyanate levels were compared. In Survey 1 the smoking prevalence was 44.1% in males and 32.9% in females, in Survey 2 45.0% in males and 26.5% in females. In agreement with previous studies it was proved that thiocyanate measurements allow to distinguish groups of non-smokers from smokers, whilst not being specific enough to reflect precisely the quantity of tobacco consumption of the individual. A quadratic regression of thiocyanate levels on cigarette consumption provided a better fit and a higher correlation coefficient than linear regression, indicating a saturation effect, i.e., there is no further increase of thiocyanate levels when more than about 30 cigarettes daily are consumed. PMID- 1889211 TI - Angiocardiographic diagnosis of ventricular septal defect localization in double outlet right ventricle. AB - Children with double outlet right ventricle, aged 3 months to 23.5 years, were examined to assess the possibility of angiocardiographic diagnosis of defect localization. It was found angiocardiography allows satisfactory localization of the defect in question. To be able localize the defect, it is critical to determine the interaction between the defect and the conus septum, and the origin of large arteries. To establish the diagnosis of ventricular septal defect, right and left ventriculography in standard and axial projections must be performed. PMID- 1889212 TI - Current status and future perspectives in the prevention of coronary heart disease. AB - The causal role of the three major coronary heart disease (CHD) risk factors - elevated plasma cholesterol, elevated blood pressure, and smoking - has become established by a wealth of scientific information which has become importantly expanded during the last decade with regard to prevention and treatment of elevated blood pressure and cholesterol lowering. A comprehensive action for CHD prevention has to include a population strategy for the reduction of risk factor levels in the entire population, and high-risk strategy for the reduction of risk factor levels in asymptomatic high-risk individuals, as well as a risk factor intervention as part of secondary prevention and good clinical care of patients with symptomatic CHD. There is no conflict between population and high-risk strategies, but instead these two different strategies are complementary to each other. PMID- 1889213 TI - Meibomian gland dysfunction in chronic blepharitis. AB - We examined 57 patients with symptoms of chronic blepharitis using meibomian gland expression, meibography, tear osmolarity, and the Schirmer's test. We also performed meibography on 20 normal patients free of chronic blepharitis. We found that 42 blepharitis patients (74%) had evidence of meibomian gland loss, whereas only four of 20 normal patients (20%) had any gland dropout. We performed cluster analysis on the data from the patients with blepharitis and found that these patients tended to fall into distinct groups with clinically relevant characteristics. We also found that tear osmolarity correlated positively with gland dropout (+0.413) and negatively with excreta volume (-0.499). This study demonstrates that an objective analysis of meibomian gland function may be used to assess chronic blepharitis and define subsets of blepharitis with measurable differences. It also supports the significance of meibomian gland dysfunction on tear osmolarity and the evaporative state of the eye. PMID- 1889214 TI - In vitro penetration of human corneal epithelium by Acanthamoeba castellanii: a scanning and transmission electron microscopy study. AB - Human corneal buttons were exposed to Acanthamoeba castellanii trophozoites and cysts for 12 hours at 35 degrees C. The buttons examined by light microscopy and scanning and transmission electron microscopy had severe epithelial ulceration and penetration by trophozoites. Observations on trophozoites below the surface suggest that penetration is accomplished by both secreted cytolytic enzymes and phagocytosis. It is likely that the secretion of one or more enzymes constitutes the initial step in preparing the host tissue for endocytosis or that the secretory mechanism is used by the amebas to move through the outer squamous layer to the basement epithelium where phagocytosis occurs. Based on this study and a previous study, it appears that entry into the cornea is a two-step process involving adherence and penetration by trophozoites. PMID- 1889215 TI - In vitro intercellular adherence of Acanthamoeba castellanii: a scanning and transmission electron microscopy study. AB - Human corneal buttons were exposed to trophozoites and cysts of Acanthamoeba castellanii for 12 hours. Examination of the buttons by scanning electron microscopy showed numerous trophozoites on the surface of the epithelium. Trophozoites examined by transmission electron microscopy had limited regions of attachment to the epithelium but extensive regions of attachment to each other. Attachment regions were characterized as plaque-like maculae of an incomplete desmosome junction. Firm attachment mechanisms may explain how penetration of the human cornea occurs. PMID- 1889216 TI - Relaxing incisions for postkeratoplasty astigmatism. AB - We report 100 cases of postkeratoplasty astigmatism, ranging from 4 to 20.5 diopters, treated with the following procedures: relaxing incisions, relaxing incisions with augmentation sutures, and repeated relaxing incisions with augmentation sutures according to the degree of astigmatism. Patients were divided into three study groups (group 1 for preoperative defects ranging from 4 to 10 diopters, group 2, from 10.5 to 15 diopters, and group 3 for defects exceeding 15 diopters). Mean preoperative astigmatism was 7.15 +/- 1.67, 12.56 +/ 1.37, and 17.50 +/- 1.51 diopters in each group, respectively. The net decrease in astigmatism after surgery was 5.53 +/- 1.44, 9.68 +/- 1.80, and 14.87 +/- 1.69 diopters in each group, respectively. Postoperatively, spectacle-corrected visual acuity improved by two Snellen lines in the group 1, five in the group 2, and nine in the group 3. The mean time to achieve stable results after surgery was 2.2 +/- 0.3, 2.7 +/- 0.4, and 4.2 +/- 0.7 months in each group, respectively (two patients in group 2 and all patients in group 3 underwent a two-step procedure). The relaxing incisions procedure, eventually modified by either adding compression sutures or repeating the incisions after 8-10 weeks, offers the possibility of a wide range of corrections for postkeratoplasty astigmatism with acceptable postoperative periods for visual rehabilitation. PMID- 1889217 TI - Tectonic keratoplasty for peripheral ulcerative keratitis. AB - Peripheral ulcerative keratitis (PUK) is a destructive, inflammatory process that can lead to corneal perforation and visual loss. Successful control of PUK has been reported with conjunctival resection, cyanoacrylate adhesive, and systemic immunosuppression. Cases with impending or actual corneal perforation may require more extensive surgery, including lamellar or penetrating keratoplasty, to maintain the integrity of the globe. We report on 17 eyes of 14 patients with PUK that required tectonic keratoplasty because of progressive ulceration. Surgery with concomitant immunosuppression preserved the eyes in all but two cases, and 8 of 17 eyes maintained or improved preoperative visual acuity. Six eyes had final visual acuities of 20/200 or better. This therapeutic strategy can preserve eyes that might otherwise be lost to progressive inflammation. PMID- 1889218 TI - Caterpillar-induced keratitis. AB - Caterpillar hairs are responsible for a well-described though infrequent form of ocular trauma and disease sometimes referred to under the term ophthalmia nodosa. Four patients with this condition are presented with a review of the pathology and treatment guidelines. PMID- 1889219 TI - Isolation of wound-specific cDNA clones from a cDNA library prepared with mRNAs of alkali-burned rabbit corneas. AB - Alkali burn is one of the most severe corneal injuries. In order to gain a better understanding of the healing of alkali-burned corneas, it is necessary to identify and characterize proteins that are specifically synthesized by the injured corneal tissues. In this study, we developed a useful procedure to identify and isolate cDNA clones that encode messenger ribonucleic acids (mRNAs) that are specific and/or abundant in alkali-burned rabbit corneas (ARCs), but absent in normal rabbit corneas (NRCs). At first, a cDNA library was prepared by cloning cDNA of mRNA isolated from ARCs into the lambda ORF-8 vector. A differential plaque hybridization was used to screen 2.5 x 10(4) plaque-forming units (pfu) from an ARC cDNA library using 32P-labeled cDNAs prepared from mRNA of ARCs and NRCs. Thirty-seven cDNA clones of mRNAs specific for ARCs were identified and isolated in their pureform. The cDNA inserts of these lambda ORF-8 phages were subcloned into the pSM216 vector by in vivo recombination. The cDNA inserts then were characterized by restriction enzyme digestion, i.e., BamHI, HindIII, and EcoRI. The size of the cDNA inserts ranged from 210 to 5,000 base pairs. Using Northern blot hybridization of total RNA prepared from polymorphonuclear neutrophils, mononuclear leukocytes, alkali-burned corneas, and normal corneas, the cDNA clones were divided into three groups. Five cDNA clones encoded mRNA of corneal cells in ARCs. Twenty-four cDNA clones derived from mRNA of inflammatory cells were present in alkali-burned corneas, but Northern blot hybridization failed to identify mRNA of discrete sizes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1889221 TI - Scleritis and Streptococcus pneumoniae. AB - We retrospectively review our experience with four patients with Streptococcus pneumoniae scleritis. Two of the patients had been exposed to beta irradiation after pterygium removal 4 and 13 years previously. One patient had a 3-year history of chronic anterior nodular scleritis, and one patient had severe rheumatoid arthritis. All were treated with intensive i.v. and topical fortified antibiotics. In two of the cases, the infection was controlled and visual acuity returned to 20/30 and 20/60. In one patient, infectious scleritis progressed to endophthalmitis. This eye ultimately became phthisical and required enucleation because of chronic pain. In the remaining patient, infectious scleritis led to perforation, which required a corneal-scleral patch graft. This patient had a final visual acuity of counting fingers. An infectious etiology should be suspected in cases of necrotizing scleritis associated with a purulent discharge, and appropriate smears and cultures should be obtained. Infectious scleritis can be caused by streptococcal organisms. Appropriate topical and intravenous antibiotic treatment is effective in some cases. PMID- 1889220 TI - Microcomputer software applied to corneal stromal biometry. AB - Here we report a new method for image analysis of the corneal stroma. To obtain the biometric characteristics of a given area, we perform three different treatments of the same image. These automated predictions closely match each parameter (length, surface area, etc.), as measured manually by a "blind investigator." Furthermore, to obtain quantifiable, average values, we have increased the number of successive image measurements, which has led to the development of a series of programs designed to optimize automated data handling. Finally, the acquired, calculated parameters are summarized in the form of intermediate tables for each series of images, and as a final summary table incorporating t-test values and permitting comparison between two stromas (e.g., normal and pathological). Multivariate analysis and an ascending hierarchical classification demonstrate the main trends in differences of pathological vs. normal stroma. PMID- 1889222 TI - Phosphatic metabolism and corneal edema. AB - From three groups of patients with corneal edema, the degree of edema was clinically quantified prior to penetrating keratoplasty. Corneas from patients with failed grafts (n = 16) had the greatest edema (mean score 3.8 +/- 0.6 SE), corneas with Fuchs' endothelial dystrophy (n = 12) had the least edema (1.4 +/- 0.4), and corneas with aphakic and pseudophakic bullous keratopathy (n = 40) had intermediate edema (2.7 +/- 0.5). Phosphorus-31 nuclear magnetic resonance spectroscopy was used to quantitate five high-energy phosphates and nine low energy phosphates and calculate 12 metabolic indices from the specimens of these three edematous groups. Corneas with aphakic and pseudophakic bullous keratopathy had lower alpha-glycerophosphate (alpha-GP) and glycerol 3-phosphorylethanolamine and glycerol 3-phosphorylcholine (GPE & GPC), and higher phosphocreatine (PCr), adenosine diphosphate (ADP), monoesters/diesters, PCr/Pi (phosphocreatine/inorganic orthophosphate), and PCr/ATP (phosphocreatine/adenosine triphosphate) than corneas with Fuchs' endothelial dystrophy (p less than 0.05). Corneas from failed grafts had lower alpha-GP, ethanolamine phosphate (EP), ethanolamine phosphate and choline phosphate (EP&CP), monoesters/Pi, ATP/Pi, and energy modulus, no detectable GPE and GPC, and higher Pi, phosphorylglycans (PG), PCr, ADP, diesters, PCr/Pi, and PCr/ATP than those with Fuchs' endothelial dystrophy (p less than 0.05). Corneas from failed grafts had lower ATP, monoesters/Pi, ATP/Pi, PCr/Pi, and energy modulus and higher Pi, PG, ADP, diesters, and PCr/ATP than corneas with aphakic and pseudophakic bullous keratopathy (p less than 0.05). In summary, there was increasing decline in the high-energy metabolites and energy status with increasing edema. PMID- 1889223 TI - Severe corneal edema after prolonged use of psychotropic agents. AB - A 23-year-old woman with schizophrenia who had been treated with a high dose of psychotropic agents for 6 years had bilateral corneal edema and suffered from severe visual disturbance. No signs of inflammation, infection, congenital abnormality, or corneal endotheliitis were observed. The symptoms did not respond to either topical or systemic treatments. Reduction in the dosage of psychotropic agents resulted in quick and complete disappearance of the corneal edema within 2 weeks. Specular microscopic examination after recovery revealed a marked enlargement of corneal endothelial cells, but there was no evidence of any corneal dystrophy. Blood-aqueous barrier function was not deteriorated, as demonstrated by aqueous protein concentration measured with a laser flare-cell meter. In conclusion, we suggest that corneal edema may be caused by prolonged use of psychotropic agents, particularly a major tranquilizer. PMID- 1889224 TI - Romberg's progressive hemifacial atrophy: an association with scleral melting. AB - We report the unusual case of a 43-year-old woman who presented with Romberg's progressive facial hemiatrophy and spontaneous scleral perforation in the ipsilateral eye, for which scleral grafting was performed. Histologic and ultrastructural examination of the scleral specimen revealed a noninflammatory lytic process. The location of the scleral loss, exactly on the line of the "en coup de sabre" atrophy, as well as the light microscopy and ultrastructural histopathologic findings suggest that the scleral destruction was a late manifestation of Romberg's disease. PMID- 1889225 TI - Conjunctival pleating and keratoconjunctivitis sicca. PMID- 1889226 TI - Keratoconus and Fuchs' endothelial dystrophy. PMID- 1889228 TI - Ultrastructural localization of alpha A-crystallin to the bovine lens fiber cell cytoskeleton. AB - Monoclonal antibodies to the bovine alpha A-crystallin were developed and used to probe the relationship between alpha A-crystallin and the bovine lens fiber cell Plasma Membrane-Cytoskeleton Complex (PMCC). Superficial bovine lens cortex was washed by repeated homogenization/centrifugation to remove "soluble protein." The resulting Plasma Membrane-Cytoskeleton Complex was covalently immobilized to inert resin, and extensively buffer washed. SDS PAGE and immunoblot analysis of both the covalently immobilized PMCC and of the sequentially-generated subcellular fractions shows that most of the lens alpha crystallin is "soluble", and readily extracted with physiologic buffers. However, this data also shows that 1) Non-alpha crystallins are progressively and quantitatively extracted from the PMCC with buffer, 2) An irreducible level of non-covalently bound alpha crystallin is achieved which cannot be readily extracted from the PMCC, even with 2 M urea, 1% NP40 or 0.4M KCl. Electron microscope level immunocytochemistry was performed on both the covalently immobilized PMCC, as well as on buffer-extracted thick frozen sections, using monoclonal antibodies to the alpha A-crystallin. The results show a very heavy labelling of both intermediate filaments and beaded filaments, but little or no labelling of fiber cell membranes. The data presented argues that a subfraction of the total alpha A-crystallin is strongly associated with the fiber cell cytoskeleton complex, and constitutes a quantitatively major component of the lens cytoskeleton fraction. PMID- 1889227 TI - Characterization of human and rabbit pigmented and nonpigmented ciliary body epithelium. AB - Nonpigmented epithelial (NPE) and pigmented epithelial (PE) cells were carefully dissected from both human and rabbit ciliary processes and have been maintained in vitro and partially characterized by morphology and immunocytochemical techniques using polyclonal and monoclonal antibodies against S-100 proteins, collagen type I and type III. The tissue distribution of these proteins was studied in formalin fixed deparaffinized tissue sections of human and rabbit eyes by immunoperoxidase staining techniques. Both NPE and PE cell lines from human and rabbit showed hexagonal morphology by light microscopy; distinct granules containing pigment could be visualized in the PE cell lines, but not in the NPE cells. Antibodies against S-100 proteins stained NPE layer intensely and PE layer slightly in the human tissue sections. The staining was less intense in rabbit tissues than human tissues. The ciliary body stroma was positive for collagen type III and negative for collagen type I or S-100. PMID- 1889229 TI - Parasympathetic denervation of the ciliary muscle following panretinal photocoagulation. AB - Cynomolgus monkeys underwent unilateral panretinal scatter photocoagulation (PRP) and/or nasal and temporal horizontal retinal meridional photocoagulation (HRMP) with xenon arc or argon or krypton laser light. Shortly thereafter, in the PRP treated eyes, accommodative responsiveness to topical eserine and electrical stimulation of the Edinger-Westphal nucleus (EWN) was diminished, accommodative responsiveness to intramuscular (i.m.) pilocarpine was enhanced, and the number of muscarinic receptors in the ciliary muscle was reduced compared to the contralateral controls. In most instances, these parameters returned to normal over 6-12 wks and the abnormalities could be induced again by another round of PRP. However, in some PRP-treated eyes, accommodative responsiveness to EWN stimulation and topical eserine remained subnormal permanently (greater than 1 yr). Shortly after HRMP alone, accommodative responses to i.m. pilocarpine, topical eserine, and central stimulation did not differ markedly in the treated and control eyes. Morphologic studies 1 to 78 wk following PRP revealed that myelinated and unmyelinated nerves within the entire circumference of the choroid and ciliary muscle were severely damaged early on. The number of unmyelinated nerves between the individual ciliary muscle fibers was drastically reduced, those which remained were swollen or deteriorated, and agranular synaptic vesicles were rarely seen. Thereafter, the nerves in the choroid and ciliary muscle gradually regenerated. Following HRMP, only the choroidal nerves which passed through the photocoagulated areas and the ciliary muscle nerves in the corresponding meridians showed signs of deterioration, and there was minimal effect on the physiologic responses examined. These findings collectively indicate that intraocular parasympathetic denervation of the ciliary muscle is produced by PRP, although all nerve types are likely damaged. PMID- 1889230 TI - Immunolocalization of arrestin (S-antigen) in rods of pearl mutant and wild-type mice. AB - The pearl mutant mouse is hypopigmented and exhibits a significantly elevated dark-adapted (DA) threshold in comparison to the congenic wild-type mouse. The primary cause of the elevated DA threshold is not known. The subcellular immunolocalization of arrestin/S-antigen reflects the state of adaptation of rod photoreceptors. In this study, quantitative immunoelectron microscopy was used to examine the subcellular distribution of arrestin in wild-type and pearl rods as a function of light exposure. The goal was to determine whether arrestin distribution within rods of pearl and wild-type mice responds to background luminance in a comparable manner. The level of arrestin immunolabeling in DA (unilluminated) rods of pearl retinas was indistinguishable from that measured in wild-type rods. By contrast, arrestin immunolabeling in light-adapted (LA) pearl rod outer segments (ROS) was significantly greater than in wild-type LA ROS. Relative to DA ROS, arrestin labeling density increased 1.6 fold in wild-type ROS following light adaptation, as compared to a 4 fold increase in pearl ROS. These data suggest that although arrestin levels in DA pearl rods are indistinguishable from that of DA wild-type rods, net changes in arrestin immunolocalization in response to light exposure reflect the effects of the pearl mutation at the level of the rod outer segment. The possible implication of this finding is discussed in view of the proposed role of arrestin in the down-regulation of the enzymatic cascade of phototransduction. PMID- 1889231 TI - Polyamines in rabbit aqueous humor after surgical trauma to the eye. AB - The polyamines putrescine, spermidine and spermine are necessary for cellular growth and directly involved in cellular differentiation and cell death. The hypothesis that extracellular polyamine levels in rabbit aqueous humor could be used as biomarkers for trauma after eye surgery was investigated. Changes in polyamine levels in rabbit aqueous humor were measured after anterior chamber lens implantation and compared to normals. The measurements were made by reversed phase HPLC and 9-fluorenylmethyl chloroformate and fluorescence detection. An increase in protein concentration followed by a white blood cell mobilization in the aqueous humor is a response to trauma to the eye. Therefore, the polyamine levels were compared to the aqueous levels of protein and leukocytes. Three days postoperatively a significant increase in spermidine was observed and a significant correlation between elevated protein levels and elevated spermine as well as total polyamines were noticed. No correlation between a high number of leukocytes and high polyamine levels were found. The results suggest that polyamines are evident markers for surgical trauma response, but not necessarily correlated to the postoperative inflammatory phase and the infiltration of inflammatory cells. PMID- 1889232 TI - Immunologic conservation of the fiber cell beaded filament. AB - Lenses were obtained from the eyes of four different classes of Chordates, including Mammalia (rat, mouse, cow, human), Aves (chicken), Amphibia (tiger salamander), and Osteichthyes (steelhead), as well as from one Mollusca (squid). Buffer soluble, urea soluble and urea insoluble fractions were prepared from each, and probed by western blot analysis for the presence of the lens fiber cell 115 and 49 kD beaded filament proteins. Application of both polyclonal and monoclonal antibodies revealed that an immunologic homologue to the bovine fiber cell 115 kD protein is present in all examples of Chordates tested, and that this homologue possessed properties very similar to those of its bovine counterpart. Both monoclonal and polyclonal antibodies revealed an immunologically cross reactive homologue in squid as well, but suggested that the squid protein had a native molecular weight of closer to 70-80 kD. A monoclonal antibody to the bovine 49 kD beaded filament protein was successful at identifying an immunologic homologue to this protein in mouse, chicken, and tiger salamander. Ultrastructural analysis of rat, human, and fish lenses showed that a beaded filament was present in these lenses, which was indistinguishable from that seen in the bovine lens. In the squid a filamentous, beaded structure was observed, but it differed from that seen in the bovine lens. We conclude from the data presented that the beaded filament, and its constituent proteins, are well conserved. This data should facilitate the identification of lens cytoskeletal proteins and structure in a wide range of animal models, and establish that probes for these proteins may be of broad applicability. PMID- 1889233 TI - Ki-67 and bromodeoxyuridine labeling of human choroidal melanoma cells. AB - Understanding tumor growth patterns has implications for prognosis as well as for response and susceptibility to treatment. The antibody Ki-67 was used as a marker of cycling cells and bromodeoxyuridine (BrdUrd) was used as a marker of proliferating cells to characterize the cycling and proliferative rates of cells from human choroidal melanoma. The BrdUrd labeling indices varied from 0-1.1% and the Ki-67 labeling indices ranged from 0-3.0.3%. Linear regression modeling showed good correlation defined by the equation: Ki-67 index = 0.237 + 1.63 x BrdUrd labeling index with r = 0.919. Correlations between these indices and clinical and histologic parameters were not significant. PMID- 1889234 TI - Covalent labelling of bovine lens multicatalytic proteinase complex with [3H]di isopropyl fluorophosphate. AB - Enzymatically active lens multicatalytic proteinase complex bound [3H]iPr2P-F after incubation for 3 hours at ambient temperature. Label was associated with the lowest molecular weight band (Mr 22,000) on sodium dodecyl sulfate polyacrylamide gels. This binding was inhibited by preincubation of the enzyme with the cysteine-directed reagent, p-chloromercuribenzoate, which inhibits all three hydrolytic activities of the enzyme. Leupeptin, which inhibits the arginyl hydrolyzing component, but not the iPr2P-F-inhibitable leucyl-hydrolyzing component of the enzyme, does not inhibit [3H]iPr2P-F binding. These data suggest that the leucy-hydrolyzing component of the lens multicatalytic proteinase complex is localized to the 22,000 Mr subunit and is a member of the thiol dependent subclass of serine proteinases. PMID- 1889235 TI - Recognition and prevention of barium enema complications. AB - The barium enema is a safe and accurate diagnostic study of the colon but, in rare cases, complications may result. Many of these can be prevented by proper equipment and careful attention to technique. When a complication does occur, prompt recognition and management is vital in decreasing morbidity and mortality. Perforation of the bowel is the most frequent serious complication, occurring in approximately 0.02% to 0.04% of patients. Rarely the colon may burst due to excessive transmural pressure alone. However, a colon weakened by iatrogenic trauma or disease is more likely to perforate during an enema than is a normal healthy bowel. Injury to the rectal mucosa or anal canal due to the enema tip or retention balloon is probably the most common traumatic cause of barium enema perforation. Inflation of a retention balloon within a stricture, neoplasm, inflamed rectum, or colostomy stoma is particularly hazardous. Recent deep biopsy or polypectomy with electrocautery makes the bowel more vulnerable to rupture. The tensile strength of the bowel wall is impaired in elderly patients, patients receiving long-term steroid therapy, and in disease states including neoplasm, diverticulitis, inflammatory bowel disease, and ischemia. Intraperitoneal perforation leads to a severe, acute peritonitis with intravascular volume depletion. The ensuing shock may be rapidly fatal. Prompt fluid replacement and laparotomy are essential. If the patient survives the initial shock and sepsis, later complications caused by dense intraperitoneal adhesions may develop. Extraperitoneal perforation is usually less catastrophic but may result in pain, sepsis, cellulitis, abscess, rectal stricture, or fistula. Intramural extravasation often forms a persistent submucosal barium granuloma which may ulcerate or be mistaken for a neoplasm. The most dramatic complication of barium enema is venous intravasation of barium. Fortunately, this is quite rare as it may be immediately lethal. Most cases have been attributed to trauma from the enema tip or retention balloon, mucosal inflammation, or misplacement of the tip in the vagina. Bacteremia has been found in as many as 23% of patients following barium enema and, in rare cases, may cause symptomatic septicemia. Other less common complications include barium impaction, water intoxication, allergic reactions, and cardiac arrhythmias. Preparatory laxatives and cleansing enemas have been implicated in some instances of dehydration, rectal trauma, water intoxication, and perforation. Careful review of the indications for examination, previous radiographs, and clinical history will identify many of the patients at greater risk for complications so that appropriate precautions may be observed.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1889237 TI - The electric guitar, eardrums, and medical meetings. PMID- 1889236 TI - Catheter pulmonary embolectomy. PMID- 1889238 TI - Helping patients choose treatments. An important role for administrative health care databases. PMID- 1889239 TI - Diffuse panbronchiolitis. PMID- 1889240 TI - Diagnostic utility of ventilation/perfusion lung scans in acute pulmonary embolism is not diminished by pre-existing cardiac or pulmonary disease. AB - The purpose of this study was to assess the impact of prior cardiac or pulmonary disease upon the utility of ventilation/perfusion (V/Q) scans in the diagnosis of acute pulmonary embolism (PE). Ventilation/perfusion scans were evaluated among 365 patients with no prior cardiac or pulmonary disease and compared to V/Q scans in 526 patients with prior cardiac or pulmonary disease. Among patients with no prior cardiac or pulmonary disease, PE was present in 117 and PE was excluded in 248. Among patients with prior cardiac or pulmonary disease, PE was present in 140 and excluded in 386. The positive predictive value for PE of high probability V/Q scans among patients with prior cardiac or pulmonary disease, 55 of 66 (83 percent), was not significantly lower than among patients without prior cardiac or pulmonary disease, 50 of 54 (93 percent) (NS). The positive predictive value of low probability V/Q scans was similar with prior cardiac or pulmonary disease, 25 of 182 (14 percent), and without prior cardiac or pulmonary disease, 17 of 113 (15 percent) (NS), as was the predictive value of near normal/normal V/Q scans, 2 of 51 (4 percent), vs 3 of 79 (4 percent) (NS). The sensitivity of high probability V/Q scans, with pre-existing cardiac or pulmonary disease and without, 55 of 140 (39 percent) vs 50 of 117 (43 percent), did not differ significantly. The specificity of high probability V/Q scans with prior cardiac or pulmonary disease and without, 375 of 386 (97 percent) vs 244 of 248 (98 percent) was also similar (NS). In conclusion, the diagnostic utility of V/Q scans for acute PE was not impaired by the presence of pre-existing cardiac or pulmonary disease. Fewer patients, however, with no prior cardiac or pulmonary disease, had intermediate (indeterminate) V/Q scans. PMID- 1889241 TI - Respi-Care. An innovative home care program for the patient with chronic obstructive pulmonary disease. AB - The purpose of the present study was to evaluate the effectiveness of a hospital based home care program for a group of patients with severe COPD. Respi-Care was a multidisciplinary home care program administered by Norwalk Hospital in cooperation with the public health nursing departments of the city of Norwalk and the town of Wilton, Conn. The overall goal of Respi-Care was to provide more comprehensive home care services to patients previously requiring frequent hospitalizations by combining the advantages of hospital resources and community agencies through a unique cooperative effort. Preprogram and on-program data were collected on the following variables for the 48 months of Respi-Care operation: hospitalizations; hospital days; emergency room visits; home care services; and the costs of these services. Costs of operating the Respi-Care program were included in on-program data. Seventeen subjects completed 320.5 months on Respi Care. Each subject was matched to an equal length of time prior to entering the program, for a total of 641 months analyzed. There were 88 preprogram hospitalizations for the group; hospitalizations while participating in Respi Care dropped to 53 (p = 0.022; paired t statistics). On-program hospital days showed a significant decrease, from 1,181 preprogram days to 667 on-program days (p = 0.024). Emergency room visits decreased from 105 before the program to 64 during the program (p = 0.017). Costs of care also decreased. Costs for hospitalizations, emergency room visits, and home care fell from $908,031 to $802,999, resulting in a $105,032 savings or $328 per patient per month.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1889242 TI - Psychological outcomes of a pulmonary rehabilitation program. AB - This study assessed physiologic, psychological, and cognitive functioning in outpatients with COPD. Sixty-four subjects, 53 to 82 years of age, participated in the 30-day exercise rehabilitation program. The program consisted of exercise, education and psychosocial counselling. Participants were assessed prior to beginning the program and at the end of 30 days. Assessments at both times included physiologic functioning (bicycle ergometry testing, pulmonary function tests, 12-min walk), psychological well-being (anxiety, depression, psychiatric symptoms, perceived well-being) and an abbreviated neuropsychological test battery. Results indicate significant improvement in physical endurance and pulmonary function, significant reductions in symptoms of depression and anxiety, and improvement in measures of general well-being and neuropsychological functioning. The study suggests that exercise rehabilitation of older adults with COPD contributes not only to improvements in physical functioning and endurance, but also to enhanced cognitive functioning and psychological well-being. PMID- 1889243 TI - Maximum intensity exercise training in patients with chronic obstructive pulmonary disease. AB - We studied high intensity, symptom-limited, endurance exercise training in 52 patients with COPD participating in a pulmonary rehabilitation program. The patients had moderate to severe airway obstruction and reduced exercise tolerance with ventilatory limitation. The target workload for endurance exercise testing was 95 percent of the baseline maximum treadmill work load. At training weeks 1, 4 and 8, they were training at 85, 84, and 86 percent respectively, of baseline maximum. After rehabilitation, there was an increase in maximal treadmill work load, VO2max, and endurance exercise time, and a decrease in perceived symptoms. Patients who did not reach anaerobic threshold (group 2) were able to train at a higher percentage of maximum exercise tolerance than patients who reached anaerobic threshold (group 1). The increase in exercise performance of both groups, however, was similar. We conclude that patients with moderate to severe COPD can perform exercise training successfully at intensity targets which represent higher percentages of maximum than typically recommended in normal individuals or other patients. PMID- 1889244 TI - The differential effect of cigarette smoke on the growth of bacteria found in humans. AB - The effect of cigarette smoke on growth of those species of bacteria that are considered common potential human pathogens was examined in vitro. Smoke from both mentholated and nonmentholated cigarettes inhibited the growth of Gram positive cocci to a greater degree than that of Gram-negative rods. Staphylococcus aureus, Streptococcus pneumoniae, and a variety of other streptococci were inhibited at a smoke solution dilution of 1:8. Enteric bacteria such as Klebsiella, Enterobacter, and Pseudomonas were not affected by a 1:1 dilution of the solution. As with the Gram-positive cocci, the Neisseria species and Branhamella were also inhibited at a dilution of 1:8. Culture results of the mouth of 15 smokers and 15 nonsmokers showed that the smokers have a propensity to develop heavy Gram-negative bacterial colonization. PMID- 1889245 TI - Screening for sleep apnea using pulse oximetry and a clinical score. AB - Confirmation of the diagnosis of OSA currently requires overnight polysomnography. This study evaluates the usefulness of pulse oximetry together with a clinical score in identifying OSA. Forty patients were assigned a clinical score based on the presence or absence of loud snoring, observations of interrupted breathing during sleep, hypersomnolence, obesity and essential hypertension. Each underwent a night of domiciliary pulse oximetry followed by nocturnal polysomnography. Significant OSA was confirmed in 26. All 15 patients with positive pulse oximetry tracings had significant OSA (apnea index greater than or equal to 10). Five of eight with negative tracings were also shown to have significant OSA along with six of the seven patients with inadequate or indeterminate tracings. Clinical scores were significantly different for those with and without OSA. This study confirms the usefulness of nocturnal pulse oximetry in establishing the diagnosis of OSA and highlights the value of a clinical score in improving its sensitivity as a screening tool. PMID- 1889246 TI - Auscultated forced expiratory time as a clinical and epidemiologic test of airway obstruction. AB - OBJECTIVE: Seeking an inexpensive, readily available, clinical, screening, and field surveillance test of airway obstruction, we determined the validity of current dogma that forced expiratory time (FET) is a good clinical test of airway obstruction yet is of no epidemiologic use given excessive intrasubject variability. SUBJECTS AND METHODS: Two hundred twenty-nine white male plumbers and pipefitters were evaluated by spirometry, chest roentgenography, and a standardized respiratory questionnaire during a union-sponsored asbestos screening program. Subjects were classified as having large airway obstruction (LAO), small airway obstruction (SAO) alone, or no obstruction, on the basis of standard spirometric prediction equations. Two physicians, blinded to clinical and spirometric data, independently measured FET while auscultating the trachea with a stethoscope. The FET was defined as the time taken for an individual to forcefully exhale through an open mouth from total lung capacity until airflow became inaudible. Five such times were recorded for each subject. The mean of the three times having the narrowest range was deemed the FET for calculating test sensitivity and specificity. Based on previous literature, an FET greater than or equal to 6 s was considered abnormally prolonged. RESULTS: Two hundred five subjects completed both spirometry and FET testing; 67 had LAO, 5 SAO, and 133 no obstruction. A total of 83 percent had three FETs reproducible within a range of less than or equal to 1 s. The sensitivity and specificity of FET for LAO were 92 and 43 percent, respectively, while for SAO alone, 60 and 44 percent, respectively. Overall, FET misclassified 56 percent of nonobstructed subjects. Adjusting the normal-abnormal cutoff points for both FET and SAO minimally improved the performance of FET. CONCLUSION: Although FET is a simple, inexpensive, sensitive, and fairly reproducible clinical test of LAO, it cannot be recommended as a clinical or an epidemiologic tool because of its extremely low specificity. PMID- 1889247 TI - Priority of peak circadian variation of bronchial responsiveness to the trough of circadian variation of bronchial caliber in asthmatic children. AB - To study the temporal relation between the peak of circadian variation of bronchial responsiveness and the trough of circadian variation of bronchial caliber, we performed seven inhalation challenges with histamine at 4-h intervals in six stable asthmatic children aged eight to ten years. Bronchial responsiveness was expressed as PC20. Coefficient of variation of baseline FEV1 within the study day was less than 7 percent in all. The trough of FEV1 variation by cosinor analysis ranged from 02.50 to 11.99 h (mean, 05.66). All had both significant (p less than 0.05) or marginally significant (0.05 less than p less than 0.1) cosinusoidal rhythm of PC20 and two or more doubling concentration differences between the highest and lowest PC20s. The trough of PC20 variation ranged from 16.32 to 02.87 h (mean, 22.30). There was a significant (p less than 0.05) difference between troughs of FEV1 and PC20 variations. We conclude that the peak of circadian variation of bronchial responsiveness precedes the trough of circadian variation of bronchial caliber in asthmatic children. PMID- 1889248 TI - Bacterial ribosomal immunostimulants prime alveolar macrophages in vivo to produce interleukin 1 in vitro. AB - Alveolar macrophages (AMs) may play a key role in human respiratory immune defenses, partially by synthesizing and releasing interleukin 1 (IL = 1). D53 (Ribomunyl), a composite bacterial ribosomal immunostimulant, has been recognized as an efficient prevention of respiratory tract infections. In vitro, D53 enhances the IL-1 production by mouse spleen adherent cells. A thymocyte proliferative response assay was used to evaluate the in vitro IL-1 production by AMs in healthy subjects who received D53 immunostimulant. Twelve nonsmoking healthy subjects took part in a prospective double-blind placebo control study. On day 1, a first bronchoalveolar lavage (BAL) was performed to assess IL-1 production by unstimulated and lipopolysaccharide (LPS) stimulated AM. Then, subjects were randomized to receive D53 (n = 6) or its placebo (n = 6) by both oral and subcutaneous injection routes from day 1 to day 15. On day 15, a second BAL was done and AM IL-1 production was again tested. IL-1 production on day 15 did not significantly differ from day 1 in both D53-treated and placebo groups either when AMs were unstimulated or were stimulated with concentrations of LPS resulting in maximal IL-1 production. However, in the D53-treated group, but not in the placebo group, IL-1 production induced by low LPS concentration (5 mg/L) was significantly higher (mean +/- SEM: 1,238 +/- 287 U/10(6) AM) on day 15 in comparison with day 1 (577 +/- 113 U/10(6) AM; p less than 0.05, Wilcoxon W test) and in comparison with the control group (day 15 IL-1 production induced by 5 mg/L LPS, 758 +/- 175 U/10(6) AM; p less than 0.05, Mann-Whitney U test). Moreover, in the D53-treated group, the optimal LPS concentration (ie, LPS concentration that induced maximal IL-1 production) was significantly lower on day 15 (mean +/- SD: 11 +/- 7 mg/L) than on day 1 (16 +/- 7 mg/L; p less than 0.05 Wilcoxon W test). We conclude that D53 immunostimulant in vivo primes AM to produce IL-1 following low LPS concentration stimulation. This may partially explain the protective effect of D53 immunostimulant against respiratory tract infection. PMID- 1889249 TI - Pulmonary function, nutrition, and self-concept in cystic fibrosis summer campers. AB - Children with cystic fibrosis (CF) often attend special summer camps. We postulated that beyond the simple fun of camp, attendance at camp might improve the clinical status and self-image of the campers. We therefore studied lung function, nutrition, and self-image in 45 children between the ages 6 and 12 years after a two-week CF summer camp. Although there was a 10 percent fall in respiratory rate during camp, spirometry did not change significantly. There were, however, significant gains in weight, skin fold thickness, and midarm circumference after two weeks at camp, and these increases were positively correlated with the number of pancreatic enzymes taken daily by the child. The Primary Self-Concept Inventory test was completed by each camper on the first and last days of camp. Although there was a trend toward increasing self-concept during camp, this did not reach statistical significance. Two weeks' attendance at summer camp appears to be associated with improved nutrition in children with CF. This may be due to increased emphasis on weight gain and appropriate use of pancreatic enzymes or to other factors, like avoidance of tobacco smoke exposure, that are unique to the summer camp setting. PMID- 1889250 TI - Pulmonary embolectomy by catheter device in massive pulmonary embolism. AB - From 1982 to 1989, ECD was performed on 18 patients suffering from poorly tolerated massive pulmonary embolism, for whom classic treatments (fibrinolytics and surgery) were impossible. Eleven of these 18 patients immediately improved (S group). This procedure was unsuccessful in other seven patients (F group). Thirteen patients survived (72 percent). The time lag between the first episode of pulmonary embolism and ECD was significantly shorter in the S group than in the F group (4.7 +/- 5.4 days vs 18.3 +/- 6.9 days, p = 0.0004). So was the elapsed time between the onset of hemodynamic impairment and ECD (13 +/- 12 hours vs 59 +/- 38 hours, p = 0.003). We conclude that ECD should be considered when other treatments are impossible especially when the first symptoms date back less than 15 days and the hemodynamic impairment less than 48 h. PMID- 1889251 TI - Comparison of oxygen desaturation during sleep and exercise in patients with cystic fibrosis. AB - Patients with cystic fibrosis (CF) desaturate during sleep and during exercise but by different mechanisms. To determine the need for supplemental oxygen, many centers measure resting and exercise arterial oxygen saturation (SaO2). We examined the associations among resting, sleep, and exercise SaO2 to ascertain the validity of this approach. We studied 21 adult and adolescent CF patients, eight of whom were hypoxemic (SaO2 less than 95 percent; group A) and 13 of whom were nonhypoxemic (SaO2 greater than or equal to 95 percent; group B) by overnight oximetry and treadmill exercise testing. The whole group desaturated more during sleep than during exercise, the change in SaO2 being 10.59 +/- 8.35 vs 6.25 +/- 4.44 (p less than 0.002). Group B desaturated significantly more during sleep than during exercise, with a reduction in SaO2 of 7.9 +/- 3.3 vs 3.3 +/- 1.49 (p less than 0.05). Group A desaturated more during exercise than group B, with a reduction of 11 +/- 3.2 vs 3.3 +/- 1.5 (p less than 0.001). Despite a strong correlation between awake SaO2 and mean sleep SaO2 (r = 0.68; p less than 0.001), minimum sleep SaO2 (r = 0.55; p less than 0.01), and minimum exercise SaO2 (r = 0.92; p less than 0.001), there was no correlation between awake SaO2 and sleep-related desaturation or between exercise- and sleep-related desaturation. In conclusion, clinically significant oxygen desaturation during sleep may be missed unless specifically checked in CF patients, and awake and exercise SaO2 may not give an indication of the degree of sleep-related desaturation. PMID- 1889252 TI - High prevalence of positive antibodies to Legionella pneumophila among outpatients. AB - A serologic survey of antibodies to Legionella pneumophila serogroups 1 through 6 was performed to assess the prevalence of positive antibody titers among outpatients and to evaluate the association between elevated antibody titers and previously identified risk factors for legionellosis. Subjects were recruited from outpatient clinics at the Minneapolis VA Medical Center. Each participant completed a self-administered questionnaire which asked about their general health and any recent symptoms of illness. Medical records were also audited for all participants to provide additional information on medical history and known risk factors for Legionella infection. Single samples of serum were obtained from each subject, and antibody titers to L pneumophila serogroups 1 through 6 were assayed. Three hundred ninety-six subjects were enrolled in the study. They had a mean age of 67 years, and 98 percent were male subjects. Overall, 36 percent of the subjects had positive antibody titers (greater than or equal to 1:128) to L pneumophila. There were no differences between those with and without elevated titers with respect to recent systemic symptoms or other previously established risk factors for legionellosis. We conclude that positive anti-Legionella antibodies are a frequent occurrence among these outpatients. This has important implications for the interpretation of single or static antibody titers from patients who are acutely ill. PMID- 1889253 TI - Routine initial computed tomography of the chest in blunt torso trauma. AB - Computer tomography (CT) is an effective technique in the initial evaluation of the abdomen and head following blunt trauma. To evaluate the role of CT of the thorax, a prospective study comparing routine early thoracic CT scanning with initial chest roentgenogram (CXR) was carried out on 73 patients with blunt torso trauma undergoing concomitant abdominal CT examination. Initial CXR and CT scans were interpreted independently by radiologists in a blinded fashion. CXR diagnosed more bony injuries than CT, while the CT identified pulmonary contusions and effusions more accurately. Only those contusions diagnosed by CXR proved clinically significant. Patient treatment was changed in one case based on CT findings. In the absence of CXR findings, chest CT scanning frequently identifies abnormalities with limited clinical significance. Although more sensitive, CT of the thorax has a limited role in the initial emergent evaluation of victims of blunt torso trauma. PMID- 1889254 TI - Action of budesonide on asthmatic bronchial hyperresponsiveness. Effects on directly and indirectly acting bronchoconstrictors. AB - We have investigated the effects of inhaled budesonide on the bronchial responsiveness to both directly and indirectly acting spasmogens in man. Following treatment with budesonide or placebo for three weeks in a double-blind, crossover trial with a three-week washout, the response to histamine and bradykinin was determined in ten patients with mild asthma. After treatment with budesonide, the response to both inhaled histamine and bradykinin was decreased when compared with placebo. The PD35 histamine was increased by 1.95 doubling doses and PD35 bradykinin by 2.1 doubling doses. Daily (PEF) recordings were significantly increased during budesonide therapy, the morning PEF by 34.8 +/- 14.1 L/min and evening by 50.3 +/- 23.1 L/min. Baseline laboratory lung function on the study days was not altered by budesonide nor were symptom records altered significantly. Inhaled budesonide therefore inhibits to the same extent the exaggerated response to both directly acting histamine and bradykinin which acts through airway nerves. PMID- 1889255 TI - Atypical pulmonary diseases associated with AIDS. AB - We present three patients with pulmonary diseases not usually associated with AIDS. Early recognition and treatment allowed a favorable outcome. The cases are discussed and the literature is reviewed. PMID- 1889256 TI - Tuberculosis diagnosed at death in the United States. AB - From 1985 through 1988, 5.1 percent of TB cases reported in the United States were diagnosed at death. Differences in the proportions diagnosed at death by race/ethnicity, sex, and place of birth (United States vs foreign-born) were relatively small. The proportion of cases diagnosed at death increased with age, from 0.7 percent in patients less than 5 years old to 18.6 percent among patients 85 years and older. Only 26.0 percent of cases diagnosed alive were among those 65 years and older, but 60.3 percent of those diagnosed at death were in this age group. Eighteen percent of cases with miliary, meningeal and peritoneal TB were diagnosed at death, compared with 4.8 percent among those with pulmonary TB. These data indicate that TB too often remains unrecognized and that, to prevent continuing deaths from this curable disease, a high index of suspicion of TB remains important, particularly among the elderly and among persons with extrapulmonary sites of disease. PMID- 1889257 TI - Antibody levels to whole culture filtrate antigens and to purified P32 during treatment of smear-positive tuberculosis. AB - Antimycobacterial IgG levels were measured repeatedly during treatment in 12 patients with moderate or severe pulmonary tuberculous disease using a dot immunobinding assay. We used reflectance densitometry equipment to quantify the immunoperoxidase staining and a Mycobacterium bovis BCG culture filtrate and the purified P32 protein as antigens. Antibody response against whole culture filtrate and P32 antigen increased after a three-month period of treatment. After this antibiotherapy was completed, the estimated amount of antibodies directed against the P32 decreased while those against the whole culture filtrate remained at the same level. A serologic test using P32 as the antigen seems to allow a better discrimination between active and healed tuberculosis. PMID- 1889258 TI - Appearance of thrombosis-inducing activity in the plasma of patients undergoing pulmonary resection. AB - Thrombosis-inducing activity (TIA) was detected in the peripheral blood of patients with lung cancer who had undergone pulmonary resection. TIA was examined by intravenously injecting plasma from the patients into BALB/c mice. The plasma containing TIA induced multiple thromboses in the lung and caused the mice to die 3 to 30 minutes after injection. The subjects were 19 patients whose plasma contained no TIA before operation. TIA was detected in 5.3 percent (1/19) on the first postoperative day (POD), 47.4 percent (9/19) on the seventh POD, 47.1 percent (8/17) on the 14th POD, 26.7 percent (4/15) on the 21st POD, and 20 percent (2/10) on the 28th POD. Plasma fibrinogen levels and peripheral platelet counts increased postoperatively and reached a maximum on the seventh and 14th POD, respectively. Peripheral blood with TIA had a significant elevation of plasma fibrinogen levels and platelet counts as compared to that without TIA. These observations suggest that TIA is present in blood in a hypercoagulable state in patients after pulmonary resection. Since tumor necrosis factor and interleukin 1 are known to induce hypercoagulable states both in vitro and in vivo, we tried to determine whether it was possible to detect both cytokines in blood indicated as hypercoagulable state by the presence of TIA. They did not, however, reach detectable levels in the blood. PMID- 1889259 TI - Effects of air pollution resulting from wire reclamation incineration on pulmonary function in children. AB - This study evaluated the effect of long-term air pollution resulting from wire reclamation incineration on pulmonary function in children. General physical examination and the determination of spirometric parameters, including forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and forced mid expiratory flow (FEF25-75%) were conducted in 400 primary school children between ages 9 and 11 years who reside in one control and three polluted areas. A survey using ATS-DLD-78-C questionnaire indicated that there were no significant differences in their demographic characteristics among children in the four areas under study. Those who had nonrespiratory diseases that might affect pulmonary function and those who failed to perform spirometric measurements were excluded from the study; therefore, 382 children were included in data analysis. The results revealed that (1) the mean values of FVC and FEV1 (expressed as percentage of predicted values calculated from Polgar's equations) in the polluted areas were significantly lower than the nonpolluted area (p less than 0.05), and (2) the incidence of pulmonary function abnormality in the polluted areas was greater than that of the nonpolluted area (p less than 0.05). The results indicated that air pollution produced by wire reclamation incineration can impair children's pulmonary function. PMID- 1889260 TI - Use of a highly purified alpha 1-antitrypsin standard to establish ranges for the common normal and deficient alpha 1-antitrypsin phenotypes. AB - Diagnosis of the hereditary disorder alpha 1-antitrypsin (alpha 1AT) deficiency is critically dependent on quantification of serum levels of alpha 1AT, a 52-kDa antiprotease that serves to protect the lung from destruction by neutrophil elastase. Although the measurement of serum alpha 1AT levels is not difficult, there is no international standard for alpha 1AT, and investigators in the field recognize that widely used commercially available standards vary by as much as 50 percent. To establish accurate ranges for the common normal and deficient alpha 1AT phenotypes, the present study uses a purified alpha 1AT standard to quantify the alpha 1AT serum levels of 443 individuals with common normal and deficient alpha 1AT phenotypes, including MM, ZZ, SS, MZ, MS, and SZ. Based on the observed values, a statistical model was developed to generate predicted frequency distributions of alpha 1AT serum levels for each of these phenotypes. Based on these studies, the ranges (5th to 95th percentile) for alpha 1AT serum levels of the common phenotypes are: MM, 20 to 53 mumol/L; SS, 20 to 48 mumol/L; ZZ, 3.4 to 7.0 mumol/L; MZ, 15 to 42 mumol/L; MS, 18 to 52 mumol/L; and SZ, 10 to 23 mumol/L. This alpha 1AT standard and these ranges are being used for the National alpha 1-Antitrypsin Deficiency Registry organized under the auspices of the National Heart, Lung, and Blood Institute. PMID- 1889261 TI - The maternal immune response in coccidioidomycosis. Is pregnancy a risk factor for serious infection? AB - Seven subjects with prior coccidioidal disease and three with active Coccidioides immitis infection during their first trimester were studied during pregnancy and postpartum to determine their general and antigen-specific cell-mediated immune status. All ten were white and carried their pregnancies to term without incident. Decreases in total lymphocytes and T-helper and T-suppressor subsets were noted during the third trimester, presumably secondary to an increase in plasma volume. Lymphocyte responses to the mitogens phytohemagglutinin, concanavalin A, and pokeweed were mildly decreased late in pregnancy, with significant intrasubject and intersubject variation. Responses to tetanus antigen were consistently and significantly lower as pregnancy progressed, rising above first trimester levels by 12 weeks postpartum. A similar pattern of response was noted with spherulin antigen for the seven subjects with previously demonstrated coccidioidal immunity. The three subjects with active coccidioidomycosis either failed to mount a significant spherulin immune response or demonstrated an early response that fell as pregnancy progressed. This antigen-specific immune suppression continued for up to 16 months postpartum despite the fact that there was no clinical evidence of coccidioidal activity beyond the first trimester. Thus, while all three completed pregnancy without complication, the data suggest that significantly increased maternal risk may be present when active coccidioidomycosis and pregnancy occur together. This risk may be greatest among darker-skinned individuals who become infected during the latter half of pregnancy. PMID- 1889262 TI - Mycobacterium gordonae: a possible opportunistic respiratory tract pathogen in patients with advanced human immunodeficiency virus, type 1 infection. AB - STUDY OBJECTIVE: To determine if Mycobacterium gordonae is an opportunistic respiratory tract pathogen in patients infected with human immunodeficiency virus, type 1 (HIV-1). DESIGN: Retrospective review of medical records of all patients with positive cultures for M gordonae from 1987 to 1989. PATIENTS: Fifteen patients had positive sputum cultures for M gordonae: five patients had AIDS or had HIV-1 infections with less than or equal to 180 CD4 cells/cu mm, and ten patients had no clinical evidence of HIV-1 infection. RESULTS: Three of the five HIV-1 infected patients had clinical, roentgenographic, and microbiologic evidence of pulmonary infection due to M gordonae that responded to antimycobacterial therapy. One of the two remaining HIV-1 infected patients had disseminated M tuberculosis and possible coinfection with M gordonae, and the other was lost to follow-up. None of the ten patients without evidence of HIV-1 infection was considered to have M gordonae respiratory tract infection. CONCLUSIONS: Sputum isolates of M gordonae should be considered potential opportunistic respiratory tract pathogens in patients with advanced HIV-1 infection and with otherwise unexplained pulmonary infection. PMID- 1889263 TI - Radionuclide evaluation of cardiac function during sleep in children with bronchopulmonary dysplasia. AB - The influence of sleep on cardiac function in severe bronchopulmonary dysplasia was assessed in five children 1.5 to 5 years of age. Left and right ventricular ejection fractions (LVEF and RVEF) were investigated by equilibrium radionuclide ventriculography in five children undergoing polygraphic monitoring during the different states of alertness: wakefulness, nonrapid eye movement sleep, and rapid eye movement sleep. Intraobserver and interobserver LVEF and RVEF measurement reproducibility was high. During quiet, supine wakefulness, LVEF was normal, but RVEF was low. During sleep, a decrease in both LVEF and RVEF, expressed as a percentage of the awake value, was marked in the two children with the most nocturnal desaturation and longest duration of paradoxic rib cage motion during inspiration. It is concluded that radionuclide ventriculography can be easily performed during sleep in children and can provide useful information regarding right ventricular function during sleep in children with severe bronchopulmonary dysplasia. PMID- 1889264 TI - Needle aspiration of extrathoracic metastases from bronchogenic carcinoma. AB - Five patients with suspected metastatic bronchogenic carcinoma underwent needle aspiration of peripheral metastatic lesions instead of a diagnostic bronchoscopy. Aspirates were from the soft tissue of the proximal arm (three patients), an axillary mass (one patient), and a skin nodule (one patient). Two patients had non-small cell carcinoma, two had small cell carcinoma, and one patient had a nondiagnostic aspirate. The procedure had insignificant morbidity, was easy to perform, quickly established a diagnosis of metastatic disease, and obviated the need for a more invasive diagnostic procedure in four of the five patients. PMID- 1889265 TI - Use of Medicare claims data to evaluate outcomes in elderly patients undergoing lung resection for lung cancer. AB - OBJECTIVE: To estimate, using Medicare claims data, the outcomes in elderly Americans undergoing lung resection for lung cancer. DESIGN: We used discharge diagnosis and procedure codes in 1983 to 1985 Medicare hospital (part A) claims records to identify patients who underwent lung resection for lung cancer; we assessed perioperative, one-year, and two-year survival using Medicare enrollment file data. PATIENTS: From a nationally random sample of 1,138,000 Medicare beneficiaries over 65 years of age, we identified 1,290 individuals who fulfilled our definition for lung resection for lung cancer. MEASUREMENTS AND MAIN RESULTS: Overall perioperative (30-day) mortality was 7.4 percent. Postoperative survival at one and two years was 69 percent and 54 percent, respectively. Male sex, older age, and pneumonectomy, as opposed to a lesser procedure, were associated with reduced perioperative and one-year and two-year survival. The adverse effect of advanced age on one-year and two-year survival following lung resection was not explained by the lower life expectancy of older individuals. CONCLUSIONS: Medicare claims data can be used to estimate likely outcomes for elderly patients undergoing surgery for lung cancer. Expected outcomes vary with the patient's age, sex, and the type of surgical procedure performed. PMID- 1889266 TI - Cine magnetic resonance imaging for diagnosis of right coronary arterial ventricular fistula. AB - In two cases of coronary arterial-ventricular fistula, detailed morphologic evaluation of the affected coronary artery was performed by MRI. Cine-MRI enabled both identification of the fistula and evaluation of the direction of shunt blood flow. Thus, MRI is a valuable noninvasive procedure in the anatomic and physiologic diagnosis of coronary arterial fistula. PMID- 1889267 TI - Effect of postural stress on left ventricular performance using the continuous wave Doppler technique. AB - To evaluate the effect of postural shifts on continuous-wave Doppler indices of left ventricular performance in normal man, we recorded Doppler signals suprasternally in 69 healthy volunteers, ranging in age from 20 to 86 years, in the supine position and 2 min after assumption of sitting and standing postures. All indices decreased progressively with increasing orthostasis: peak acceleration (PKA): 15.6 +/- 4.5 m/s2 to 14.0 +/- 4.0 m/s2 to 13.6 +/- 4.6 m/s2; peak velocity (PKV): 0.64 +/- 0.18 m/s to 0.58 +/- 0.17 m/s to 0.56 +/- 0.17 m/s; stroke distance (SD): 11.4 +/- 3.7 cm to 9.8 +/- 3.4 cm to 8.0 +/- 2.8 cm; SD x heart rate (VIH): 717 +/- 272 cm to 655 +/- 268 cm to 572 +/- 217 cm, from supine to sitting to standing, respectively (p less than 0.001). In contrast heart rate increased modestly from 62.4 +/- 10.0 bpm supine, to 66.9 +/- 12.4 bpm sitting, to 71.3 +/- 9.9 bpm standing (p less than .001). Similar postural changes in Doppler variables were seen in all three age groups (20 to 44 years; 45 to 64 years; and 65 to 86 years). Thus, orthostasis in normal subjects is accompanied by a reduction in all continuous-wave Doppler indices of left ventricular performance, regardless of age. PMID- 1889268 TI - Right ventricular pacing and left ventricular filling pattern. An echo-Doppler study. AB - The influence of right ventricular pacing on left ventricular filling has not been completely clarified. The aim of the study was to analyze the possible alteration in and effects on left ventricular filling resulting from right ventricular pacing. The study population consisted of two groups; group A was comprised of 12 patients with a spontaneous left bundle branch block, and group B had 12 patients without left bundle branch block. All the patients underwent an interrogation of the mitral valve inflow by Doppler echocardiography, in order to measure isovolumic relaxation time, early and late peak velocity (E and A wave), E/A ratio and deceleration time. The study was performed at spontaneous rhythm and after, inhibition of the pacemaker. In group A, there were no changes in the Doppler parameters when passing from a spontaneous to an 80/min electrically induced rhythm. Analysis of group B revealed a statistically significant lengthening of IVR and Dec t with electrical stimulation. No statistically significant differences were found when we compared the Doppler parameters of the two populations at the same pacing frequency. Right ventricular pacing causes interventricular asynchrony and abnormalities in diastolic filling times, which resulted in a lengthening of either IVR and Dec t, simulating a pattern of abnormal relaxation. PMID- 1889269 TI - Diastolic time in diabetes. Impairment of diastolic time during dynamic exercise in type 2 diabetes with retinopathy. AB - To evaluate the effect of microangiopathic complications and autonomic dysfunction on diastolic time (DT) during dynamic exercise, 19 patients with type 2 diabetes and ten normal subjects were studied using ear densitography. All subjects had neither an ischemic electrocardiographic response nor chest pain during maximal treadmill exercise. The DT and heart rate (HR) had an inverse nonlinear relation, and electromechanical systole (QS2) and HR had an inverse linear relation during exercise. When the exercise DT-HR and QS2-HR relations were compared, a significant lengthening of QS2, with a consequent shortening of DT, was observed in diabetic patients with retinopathy, compared to patients without retinopathy and normal subjects (p less than 0.005), while no significant differences were found between diabetic patients without retinopathy and normal subjects; however, there were no significant differences in the exercise DT-HR and QS2-HR relations among diabetic patients with and without autonomic dysfunction and normal subjects. A more prominent abbreviation in the diastolic perfusion time observed in patients with retinopathy would be meaningful because microangiopathy might already have limited subendocardial blood flow. Thus, patients with type 2 diabetes who have retinopathy have a potential risk of aggravation of left ventricular function through the deterioration of myocardial blood flow. PMID- 1889270 TI - The value of portable chest roentgenography in adult respiratory distress syndrome. Comparison with computed tomography. AB - In 17 patients with adult respiratory distress syndrome, we used data derived from computed tomographic (CT) scan densitometric analysis to validate the value of portable chest roentgenograms in objectively estimating the amount of pulmonary edema. Chest roentgenograms and CT scans were taken in the same ventilatory conditions (apnea at 10 cm H2O of positive end-expiratory pressure [PEEP]); blood gas samples and hemodynamic parameters were collected at the same time. Roentgenographic analysis was undertaken by independent observers using two standardized scoring systems proposed in the literature. CT scan analysis was performed using the CT number frequency distribution and the gas lung volume (measured by helium dilution technique) to estimate quantitatively the lung density, the lung weight, and the percentage of normally aerated and nonaerated tissue. Knowing the mean CT number of the pulmonary parenchyma in a group of normal subjects, we also inferred the ideal lung weight expected in the study population and computed the excess tissue mass as the difference between actual and ideal lung weight. Both the roentgenographic scoring systems showed direct correlation with the pulmonary impairment as detected by CT scan densitometric analysis (CT number, percentage of nonaerated tissue, lung weight, and excess tissue mass; p less than 0.01) and inverse relation with the percentage of normally aerated tissue (p less than 0.01). We also found a relationship between roentgenographic scores and the impairment in gas exchange as detected by shunt fraction (p less than 0.05). We conclude that standardized reading of portable chest roentgenograms by means of scoring tables is a valuable tool in estimating the amount of pulmonary edema in a patient with adult respiratory distress syndrome. PMID- 1889271 TI - Serial measurement of pulmonary mechanics assists in weaning from extracorporeal membrane oxygenation in neonates with respiratory failure. AB - Extracorporeal membrane oxygenation (ECMO) is a highly invasive therapy for intractable neonatal respiratory failure, and serious complications may occur with increasing duration of bypass. Weaning from bypass is empirical at present. Thus, there is a need to accurately predict when infants can be successfully decannulated. We hypothesized that pulmonary mechanics would reflect lung recovery and, therefore, predict successful weaning from ECMO. We measured pulmonary mechanics daily in 22 neonates, at gestational age of 37.8 +/- 0.6 weeks (SE) requiring ECMO for severe respiratory failure (oxygen index 66 +/- 6). Pulmonary resistance (Rpul), dynamic compliance (Cdyn), and tidal volume (VT) were measured. Rpul did not predict lung recovery. Cdyn within 24 hours of starting ECMO was 0.3 +/- 0.04 ml/cm H2O. Cdyn within 24 hours of weaning from ECMO was 1.2 +/- 0.09 ml/cm H2O (p less than 0.001). All 22 infants had Cdyn greater than 0.6 ml/cm H2O at the time of decannulation, but four infants (20 percent) with Cdyn less than 0.6 ml/cm H2O could not be weaned from ECMO within 20 hours (p less than 0.01). Thus, a minimum Cdyn of 0.6 ml/cm H2O is associated with successful weaning from ECMO. Cdyn of 0.8 ml/cm H2O provided better overall discrimination between those who could be successfully weaned from ECMO. We conclude that serial measurement of dynamic pulmonary compliance predicts successful weaning from ECMO. PMID- 1889272 TI - Nasal positive pressure ventilation in patients with acute respiratory failure. Difficult and time-consuming procedure for nurses. AB - Intubation and mechanical ventilation are well-established techniques in the management of patients with acute respiratory failure; however, there are situations in which these procedures cannot be used safely for various reasons. A recently described noninvasive technique, nasal positive-pressure ventilation (NPPV), has been developed for home ventilation of certain patients with chronic ventilatory insufficiency. We hypothesized that NPPV could be used in selected patients in whom intubation and mechanical ventilation were clearly indicated, but not immediately possible, or even contraindicated. Six patients were treated with NPPV during an episode of acute respiratory failure and enrolled in a prospective study. We found that NPPV was successful in avoiding intubation, but only in the three patients suffering from a restrictive pulmonary disorder, whereas the procedure was unsuccessful in patients with obstructive disorders. Moreover, in every patient, acute NPPV was very time-consuming for the nursing staff: in patients with restrictive disorders, a nurse had to monitor a patient submitted to NPPV during 41 +/- 9 percent of the duration of ventilation and during 91 +/- 9 percent of the NPPV time in patients with obstructive disorders. We conclude that acute NPPV may be attempted in selected patients with acute respiratory failure, predominantly patients with restrictive respiratory disorders, but that this procedure is very time-consuming for nurses. PMID- 1889273 TI - Antibiotic prophylaxis of respiratory tract infection in mechanically ventilated patients. A prospective, blinded, randomized trial of the effect of a novel regimen. AB - The objective of this study was to assess the effect of a novel regimen of antibiotic prophylaxis on the incidence of lower respiratory tract infection in patients requiring prolonged (at least five days) mechanical ventilation. The design was a controlled, prospective, randomized trial, with blinded comparison of the groups regarding the incidence of respiratory tract infection in an intensive care unit of a university hospital. After determination of the APACHE II score for severity of disease, 88 patients were randomly divided in three groups. Twenty-four of these patients did not complete five days of mechanical ventilation, and eight were withdrawn for other reasons. Fifty-six patients (18 in group 1, 21 in group 2, 17 in group 3) completed the study. Patients in both control groups 1 and 2 did not receive antibiotic prophylaxis, but the two groups differed in the antibiotic policy in case of infection. Patients in group 3 received antibiotic prophylaxis consisting of norfloxacin, polymyxin E, and amphotericin B, applied topically in oropharynx and stomach from time of ICU admission until extubation, and intravenous cefotaxime 500 mg three times a day during the first five days of admission. In both control groups, about 90 percent of the patients acquired microbial colonization of oropharynx or stomach. In group 3, only 12 percent and 24 percent of the patients acquired colonization of oropharynx and stomach, respectively (p less than 0.001). This resulted in a reduction of the incidence of lower respiratory tract infection (78 percent in group 1, 62 percent in group 2, 6 percent in group 3 [p = 0.0001]). The regimen of antibiotic prophylaxis studied prevented respiratory tract infection in mechanically ventilated patients. Antibiotic prophylaxis should be considered in all patients expected to require prolonged mechanical ventilation. PMID- 1889274 TI - Effects of high- and low-carbohydrate meals on maximum exercise performance in chronic airflow obstruction. AB - The purpose of this study was to compare the effects of isocaloric liquid meals with high fat (55 percent) and low carbohydrate (28 percent) content (Pulmocare) to meals with low fat (30 percent) and high carbohydrate (53 percent) content (Ensureplus) on exercise performance in subjects with chronic airflow obstruction (CAO). Twelve stable subjects with CAO (FEV1 = 1.30 +/- 0.47 L) underwent incremental symptom-limited exercise tests 90 minutes following the ingestion of 920 calories of EnsurePlus HN (E), 920 calories of Pulmocare (P), or a noncaloric placebo (C). Tests were performed on three days, in a double-blind randomized fashion. Expired gases were collected continuously and analyzed every 30 seconds. The mean maximal work load after E (81 +/- 24 W) was significantly less than that after P (88 +/- 21 W) or C (88 +/- 24 W). The mean ventilation at exhaustion was similar after E (48 +/- 13 L/min), P (51 +/- 11 L/min), and C (49 +/- 10 L/min). In comparison to C, six of the 12 individuals had a decreased work load following E, while only one had a decreased maximal tolerated work load following P. The results of this study suggest that meals with a higher fat and lower carbohydrate content may be less likely to impair work performance of patients with CAO in the absorptive phase than meals with a lower fat and higher carbohydrate content. These findings may have clinical significance to patients with CAO who complain of postprandial exertional dyspnea. PMID- 1889275 TI - Norepinephrine and phenylephrine effects on right ventricular function in experimental canine pulmonary embolism. AB - In a canine model of pulmonary embolism (PE) produced by infusion of autologous blood clots, mean arterial blood pressure (MAP) decreased to 73 +/- 4 mm Hg while cardiac output (CO) decreased to less than 50 percent of baseline. Intravenous infusion of phenylephrine (PHEN) and norepinephrine (NE) restored MAP to somewhat above baseline values. However, only NE restored CO to control levels. The right ventricular myocardial blood flow increased 15 percent in the PE group with PHEN and 229 percent with NE at equipressor concentrations. The right ventricular myocardial oxygen consumption (RVMVo2) was not significantly different between PE and PE + PHEN while PE + NE increased RVMVO2 by 144 percent to 20.2 +/- 1.8 ml/min/100 g. The RV output was not adequately restored with PE, but when RV contractility was augmented with NE, RV output was restored to baseline. Right ventricular minute work increased 100 percent with NE and was maintained with a 100 percent increase in oxygen consumption. Calculated pulmonary vascular resistance (PVR) was decreased during PE by 36 percent with PE + PHEN while PVR in NE-treated dogs decreased by 59 percent. In NE-treated animals, systemic vascular resistance (SVR) was restored to control levels while in PHEN-treated animals SVR increased about 75 percent from baseline. We conclude that the salutary effects of NE on RV output are due to both alpha and beta receptor stimulation, which increased contractility, RVMBF, and RVMVo2, and decreased both PVR and SVR. In the PHEN-treated dogs, our indices of minute-work, RVMBF, and RVMVo2 suggest that coronary autoregulation was intact; however, there was no apparent benefit to RV output. This study suggests that in the clinical setting of acute PE, the judicious use of NE, rather than PHEN, may be more beneficial in restoring RV function and systemic hemodynamics. PMID- 1889276 TI - Gram-negative sepsis. Background, clinical features, and intervention. AB - Gram-negative sepsis remains an urgent medical problem, with more than 200,000 cases occurring each year in the United States and an associated mortality rate of 20 to 50 percent. Since the onset of shock greatly worsens prognosis and to encourage early intervention, the term sepsis syndrome was developed to describe the features of a preshock septic state. Early clinical and metabolic indicators are discussed, and current therapy is reviewed. Better understanding of the pathophysiology of endotoxin release from Gram-negative bacteria and advances in biotechnology have led to the development of potential new treatments for sepsis. One such development--monoclonal antibodies to endotoxin--has shown great promise in the effort to block the progression to septic shock, reduce mortality, and decrease the overall costs of sepsis to the patient and to the national economy. PMID- 1889277 TI - A man with a large trachea. PMID- 1889278 TI - Right-sided chest pain with progressive dyspnea. PMID- 1889279 TI - A follow-up visit with Dr Dickens. PMID- 1889280 TI - Surgical treatment of lung cancer. PMID- 1889281 TI - Endobronchial treatment of lung carcinoma. PMID- 1889282 TI - Neoadjuvant therapy of lung cancer. PMID- 1889283 TI - Tranexamic acid treatment of hemothorax in two patients with malignant mesothelioma. AB - Patients with malignant mesothelioma may present with hemothorax. We used a combination of oral and intrapleural tranexamic acid to treat two patients with this severe complication. Initiation of treatment with this potent anti fibrinolytic drug resulted in rapid reduction of bleeding and of transfusion requirements. PMID- 1889284 TI - Use of TAO without methylprednisolone in the treatment of severe asthma. AB - The antimicrobial agent troleandomycin (TAO) has been shown to be effective in reducing corticosteroid requirements in patients with corticosteroid-dependent asthma. To our knowledge, the efficacy of TAO without concomitant use of corticosteroids has never been documented. We report the case of a 12-year-old patient with corticosteroid-dependent asthma who has remained asymptomatic and without any evidence of pulmonary deterioration during treatment with TAO without concomitant use of corticosteroids. PMID- 1889285 TI - Reversible tricuspid stenosis. Demonstration with two-dimensional echocardiography and continuous-wave Doppler. AB - We report a case of pseudo-tricuspid stenosis as a result of extrinsic compression of the tricuspid valve by a large right-sided pericardial effusion. Two-dimensional echocardiography and continuous-wave Doppler enabled accurate noninvasive diagnosis and hemodynamic assessment. PMID- 1889286 TI - Chronic reactive airway disease following acute chlorine gas exposure in an asymptomatic atopic patient. AB - While chlorine gas inhalation has previously been reported to cause temporary mucous membrane irritation, acute pneumonitis, pulmonary edema, and transient bronchospasm, there is controversy about the existence of long-term pulmonary sequelae. We report the case of a 25-year-old man in whom chronic, recurrent asthma developed after exposure to a chlorine gas leak in an enclosed space. His course since the exposure has been notable for frequent exacerbations necessitating chronic corticosteroid therapy and multiple hospitalizations. To our knowledge, the persistence of symptoms years after the exposure is unique in the literature. PMID- 1889287 TI - Pulmonary Kaposi's sarcoma presenting as fulminant respiratory failure. AB - A 32-year-old black man, a homosexual patient with a history of lymphadenopathy, presented with diarrhea, weight loss, and a bilateral interstitial infiltrate. Within days after admission, the patient developed dyspnea with rapid progression to respiratory failure and a rapid increase of the infiltrate. An open-lung biopsy showed Kaposi's sarcoma. Treatment with chemotherapy reversed the respiratory failure. PMID- 1889288 TI - Mycoplasma pneumoniae as the causative agent for pneumonia in the immunocompromised host. AB - A young man undergoing chemotherapy for Ewing's sarcoma presented with fever, neutropenia, anemia, thrombocytopenia, and a new infiltrate on the chest roentgenogram. Routine cultures and cytopathologic examination of bronchoalveolar lavage fluid provided no evidence for an etiology; however, special cultures of the BAL fluid demonstrated heavy growth of Mycoplasma pneumoniae. We recommend that evaluation of pneumonia in the immuno-compromised host include appropriate cultures of BAL fluid for M pneumoniae, particularly when the patient is 5 to 25 years old, the age of high incidence of mycoplasmal pneumonia. PMID- 1889289 TI - J-shaped catheter for endobronchial aspiration of right upper lobe bronchus during rigid bronchoscopy in pediatric patients. AB - A J-shaped suction catheter was tailored to facilitate aspiration of the right upper lobe bronchus during rigid bronchoscopy in pediatric patients. This suction catheter was used successfully in three patients. PMID- 1889290 TI - Bronchoalveolar lavage neutrophilia seen in Pneumocystis pneumonia presenting with pneumothorax. AB - Spontaneous pneumothorax is a known complication of Pneumocystis carinii pneumonia (PCP) in patients with acquired immunodeficiency syndrome. From a series of 61 patients with PCP, we identified two cases, not associated with aerosolized pentamidine, that presented with spontaneous pneumothorax and cystic changes seen on chest radiographs. Bronchoalveolar lavage cell findings were remarkable for very elevated neutrophil counts in both cases, suggesting a possible inflammatory cause for the observed cystic changes. PMID- 1889291 TI - Percutaneous balloon valvotomy for the treatment of isolated tricuspid stenosis. AB - A 46-year-old woman with isolated tricuspid stenosis complained of increasing fatigue and dyspnea on exertion. Exercise Doppler echocardiography reproduced her symptoms and revealed a marked increase in trans-tricuspid gradient. Successful percutaneous balloon tricuspid valvotomy was performed, with resolution of her symptoms. PMID- 1889292 TI - Anterior mediastinal tumor of 30 years' duration. AB - A 67-year-old woman had a large mediastinal mass with calcification. On roentgenogram of 30 years ago, the same mass without calcification was seen. The mediastinal mass was removed by surgery and proved to be a non-Hodgkin's lymphoma (NHL), most probably as a transition from a giant lymph node hyperplasia (Castleman's disease). PMID- 1889293 TI - Massive ST-segment elevation without myocardial injury in a patient with fulminant hepatic failure and cerebral edema. AB - A 49-year-old woman presented in fulminant hepatic failure. The ECG showed dramatic ST-segment elevation, suggesting diffuse myocardial injury. However, echocardiography, creatine phosphokinase enzyme determinations, and examination of the heart at autopsy (six days later) failed to demonstrate any physiologic, anatomic, or histologic evidence of abnormality. The appearance of ST-segment elevation in this setting should not prompt treatment for cardiac disease or limit the candidacy for liver transplantation of such critically ill patients. PMID- 1889294 TI - Prostaglandin F2 alpha and indomethacin in hepatogenic pulmonary angiodysplasia. Effects on pulmonary hemodynamics and gas exchange. AB - We treated a 68-year-old man with cirrhosis of the liver associated with moderate hypoxemia. Contrast-enhanced echocardiography revealed late opacification of the left ventricle, and pulmonary perfusion imaging with 99mTc macroaggregated albumin showed evidence of a significant uptake in both lungs and in the liver, spleen, and kidneys. Right cardiac catheterization revealed pulmonary hypotension, low pulmonary vascular resistance, and high cardiac output. We administered prostaglandin F2 alpha intravenously (0.2 microgram/kg/min for 30 minutes) and indomethacin orally (75 mg/day for three days). There was some degree of resolution of the hypoxemia and increases in both pulmonary arterial pressure and pulmonary vascular resistance. These findings suggest that the pathophysiology of hepatogenic pulmonary angiodysplasia is a reversible intrapulmonary vascular dilatation. These conditions can to some extent be modulated by vasoactive substances such as prostaglandins or other eicosanoids. PMID- 1889296 TI - The thoracic vent. Clinical experience with a new device for treating simple pneumothorax. AB - We report recent experience with a new device, the thoracic vent, in the management of simple pneumothorax. There were 16 patients aged 19 to 73 years who suffered pneumothorax due to spontaneous (4), traumatic (3), or iatrogenic (9) causes. Ease of insertion, patient tolerance, and the presence of a unique signal diaphragm all contributed to patient and physician acceptance of the device. Average time to pneumothorax resolution was 2.5 days, and time to thoracic vent removal averaged 3.2 days. There were no immediate recurrences or significant complications. We conclude that the thoracic vent is an effective device for initial and definitive therapy of simple pneumothorax. PMID- 1889295 TI - Fatal pulmonary aspergillosis presenting as acute eosinophilic pneumonia in a previously healthy child. AB - A previously healthy boy presented with cough and diffuse pulmonary interstitial infiltrates. Acute eosinophilic pneumonia was diagnosed by bronchoalveolar lavage in the absence of a demonstrable infectious etiologic agent. Corticosteroid therapy resulted in immediate improvement but was followed by respiratory distress and death from invasive aspergillosis and Pseudomonas cepacia sepsis. PMID- 1889297 TI - Scorpion envenomation. PMID- 1889300 TI - Intravenous etoposide therapy and intractable hiccups. PMID- 1889299 TI - Complications of thoracostomy. PMID- 1889298 TI - Cardiac arrhythmias during theophylline toxicity. PMID- 1889301 TI - Chest wall vascular malformations. PMID- 1889302 TI - Nocardiosis mimicking pulmonary tuberculosis in Ugandan AIDS patients. PMID- 1889304 TI - In vitro activity of lomefloxacin, a difluorinated quinolone, compared with other antimicrobials. AB - A total of 3,144 clinical isolates from 3,011 consecutive patients were tested against lomefloxacin by the agar dilution method. They consisted of 1,380 isolates of Enterobacteriaceae, 527 pseudomonads, 47 Haemophilus influenzae, 53 Acinetobacter, 42 Brucella melitensis, 903 staphylococci and 192 strains of enterococci. In vitro activity of lomefloxacin was compared with ciprofloxacin, norfloxacin, beta-lactams and aminoglycosides. Over 98% of Enterobacteriaceae were susceptible to lomefloxacin with an MIC of 0.06-4.0 micrograms/ml. It also inhibited 93 and 85% clinical isolates of Pseudomonas aeruginosa and Xanthomonas maltophilia, respectively. All isolates of Haemophilus, Brucella and Staphylococcus aureus were susceptible to this fluoroquinolone. However, only 43% of the 192 strains of enterococci exhibited in vitro susceptibility. Lomefloxacin was found to be comparable to ciprofloxacin and norfloxacin in its in vitro activity, and superior to most penicillins, cephalosporins and aminoglycosides against both gram-negative and gram-positive bacteria except enterococci. PMID- 1889303 TI - In vitro and in vivo candicidal activities of 2-(p-n-hexylphenylamino)-1,3 thiazoline. AB - The 2-amino-1,3-thiazoline, 2-(p-n-hexylphenylamino)-1,3-thiazoline (MDL 20,245) killed 10(5) logarithmic or stationary phase Candida albicans/ml in less than 1 h. Miconazole killed logarithmic phase cells at that rate, but miconazole, clotrimazole or econazole killed stationary phase cells at a slower rate of 10(2) 10(4) cells/ml in 24 h. MDL 20,245 induced efflux of K+ and L[U-14C] lysine from C. albicans, indicating that the candicidal mechanism is to exert direct damage upon the cytoplasmic membrane. The activity of MDL 20,245 in vitro was antagonized by fatty acids, triglycerides and phospholipids. Topical application of MDL 20,245 ointment (10% w/v) twice per day for 4 days to rats suppressed C. albicans-induced vaginitis 100%. Single-dose regimens of MDL 20,245, miconazole or clotrimazole correlated with 97, 90 and 73% suppression, respectively. These data suggest that MDL 20,245 may be effective in the treatment of C. albicans induced vaginitis in humans. PMID- 1889305 TI - Variation in induction of chromosomal beta-lactamase expression in strains of Enterobacter cloacae. AB - Eight strains of Enterobacter cloacae with varying patterns of susceptibility to beta-lactam antibiotics were studied to compare the inducibility and expression of their beta-lactamase genes. These strains included two isolates from one patient, which differed in their susceptibility to cefamandole. A resistant strain constitutively produced large amounts of beta-lactamase; a sensitive strain produced an inducible beta-lactamase. Study of induction and growth characteristics of all strains revealed that the induction and the expression of inducible beta-lactamase genes may vary considerably among strains of E. cloacae. PMID- 1889306 TI - Turbidimetric study of the effect of inoculum density on the response of Escherichia coli to gentamicin under aerobic and anaerobic conditions. AB - The turbidimetric response to gentamicin of two strains of Escherichia coli was examined under aerobic and anaerobic conditions with 3 inocula. Turbidimetry showed that the minimum inhibitory concentration (MIC) was influenced by growth of partially inhibited cultures during the overnight incubation period. Continuous turbidimetric monitoring also allowed the minimum antibacterial concentration (MAC: the lowest concentration to cause an effect on normal growth) to be measured. As judged by the MAC, the effect of inoculum was small over the range 5 x 10(5) to 9 x 10(7) colony-forming units (CFU), but increased substantially as the inoculum was raised further. Exposure to gentamicin under anaerobic conditions caused an average 4-fold rise in the MAC with different inocula. PMID- 1889307 TI - Bactericidal effect of 15-deoxyspergualin on Staphylococcus aureus. AB - 15-Deoxyspergualin (DSG), an immunosuppressive agent used in organ transplantation, exerts metabolic and antiproliferative effects on methicillin- and gentamicin-resistant Staphylococcus aureus and other bacteria (e.g. Sarcina lutea, Bacillus subtilis, Shigella sonnei, Salmonella typhi and Citrobacter freundii). DSG, at the concentration of 20 mg/l, depleted intracellular putrescine and spermidine in S. aureus to 43 and 40% of the controls, respectively. In these polyamine-depleted S. aureus cells, the synthesis of protein, DNA and RNA was decreased to 20, 85, 78% of the controls. The minimal inhibitory concentrations (MIC) of DSG for growth of S. aureus, S. lutea, B. subtilis, S. sonnei, S. typhi and C. freundii were 17, 13, 7, 15, 4, and 29 mg/l, respectively. PMID- 1889308 TI - Inhibitory effect of tachyplesin I on the proliferation of human immunodeficiency virus in vitro. AB - An antimicrobial peptide, tachyplesin I, isolated from hemocytes of the Japanese horseshoe crab (Tachypleus tridentatus) was examined for its inhibitory effects on human immunodeficiency virus (HIV) infection in vitro. At a concentration of 7.5 micrograms/ml, tachyplesin I suppressed the development of cytopathic effects (CPE) by more than 70% in MT-4 cells infected with HIV (lymphadenopathy associated virus). This inhibitory effect was observed only when the drug was added during the adsorption period of the virus to the cells. In cocultures of MOLT-4 and persistently HIV-infected cells (MOLT-4/HIV), tachyplesin I at the same concentration completely inhibited multinucleated giant cell formation. Infectivity of HIV was reduced by 10(-2.5) in medium free from fetal calf serum containing tachyplesin I at a concentration of 200 micrograms/ml. Tachyplesin I did not show any inhibitory effect on reverse transcriptase activity of HIV at concentrations of 9-80 micrograms/ml at which tachyplesin I inhibited HIV infection. These results suggest that the anti-HIV action of tachyplesin I was due to the inhibition of virus adsorption. PMID- 1889309 TI - Influence of human urine on the in vitro activity and postantibiotic effect of ciprofloxacin against Escherichia coli. AB - The purpose of this investigation was to study the effects of human urine on the minimum inhibitory concentration (MIC) and the postantibiotic effect (PAE) of ciprofloxacin against Escherichia coli. MICs and the PAE were performed in Mueller-Hinton broth (MHB; pH 7.3 and 5.5) and in human urine (pH 5.5 and 7.3). In urine, pH 5.5, MICs increased 64-fold (from 0.016 to 1.024 micrograms/ml) and the PAE was abolished (from 101.6 to 3.7 min), when compared to MHB, pH 7.3. An acidic pH demonstrated the greatest effect on reduced susceptibility and PAE. Using ciprofloxacin concentrations adjusted for a higher MIC obtained in pH adjusted urine and MHB, PAE values were similar for urine and MHB (approximately 280 min at 40 x MIC). This study demonstrated that the MIC and PAE of ciprofloxacin against E. coli are influenced by human urine and in particular its pH. PMID- 1889310 TI - Ambivalences: a challenge to permanency for children. AB - A key to determining a permanent plan for children in placement lies in determining and working with the history and relative intensity of parental ambivalence in the parent-child relationship as it is acted out in the placement experience. A study of cases in a public department disclosed not only indicators of parental ambivalence but also the reinforcement of that ambivalence by agency policy, working conditions, and lack of resources. PMID- 1889311 TI - Competency-based evaluation of case-management skills in child sexual abuse intervention. AB - A model training protocol for case management of child sexual abuse cases, with a concomitant competency-based evaluation of these skills, is presented. Findings suggest that relative to skills in problem identification, child protective service workers need training in formulating goals and objectives and negotiating contracts with sexually abusive families. PMID- 1889312 TI - Innovations in child protective services inservice training: commitment to excellence. AB - The overwhelming obstacles to effective CPS intervention created by increasing reports of abuse and neglect, funding shortfalls, and the lack of qualified workers have prompted national efforts to reform the public child welfare system in the United States. Organizations such as the American Public Welfare Association, the Children's Defense Fund, the Child Welfare League of America, and the National Association of Social Workers are currently working closely with other national organizations to develop legislative proposals that will enable child welfare agencies to be more responsive to the needs of children and families. A critical component of this reform is the need to recruit, train, and retain qualified and competent CPS workers. The four training programs described in this article are examples of innovative programs seeking to enhance service delivery by enhancing the knowledge and skills of their staff members. Although the four programs were developed in very different political and social climates and within diverse organizational structures, they all provide useful lessons in how to develop efficient and effective training for workers delivering protective services for children. Any national, state, or local efforts to design and develop new CPS training programs should take into account the significant strides made by these agencies. PMID- 1889314 TI - Comparative perspectives on child abuse and neglect: Chinese versus Hispanics and whites. AB - In a quota sample of 150 individuals, equally divided among Chinese, Hispanics, and whites, it was found that the Chinese were more tolerant of parental conduct than the Hispanics and whites, and were less likely to ask for investigation by protective agencies in potential cases of child abuse and neglect. The Chinese attitude is explained in part by well-known features of traditional Chinese culture, such as filial piety and familism. In addition to contributing to a transcultural understanding of child mistreatment, the study calls for heightened sensitivity in approaching issues of abuse and neglect in minority groups. PMID- 1889313 TI - Pediatricians and foster children. AB - The poor state of health and health care of foster children is well documented. The cure lies in the hands of the agencies that administer the foster care system and pay for medical services, and in those of the physicians who provide that care. This study suggests that much of the problem may be solvable. Adequate numbers of pediatricians in Connecticut seem to be committed to caring for foster children, but major impediments remain, including inadequate reimbursement for both primary and specialty health services. The institution of a medical passport can make needed information available and help to establish and promote standards of care. Pediatricians appear willing to take a leadership role in assisting other agencies in developing programs to improve the care of these children; despite the problems in providing medical care to foster children, most pediatricians view it as part of their responsibility to the community and to all children. PMID- 1889315 TI - Use of court-appointed advocates to assist in permanency planning for minority children. AB - Despite federal law on reuniting children in care with their families, minority children remain in dependency longer and are more likely to be placed in long term foster care than white children. This article describes a program of volunteer, court-appointed advocates to assist in cases of abuse and neglect involving minority families, and an outcome study. Significantly fewer children were placed in long-term foster care and significantly more children were placed in adoptive families than in a comparison group of families. PMID- 1889316 TI - Toward a clearer differentiation of high-risk from low-risk fire-setters. PMID- 1889317 TI - [Changes of calcitonin gene-related peptide (CGRP) concentrations in CSF in patients with cerebrovascular disorders]. AB - Concentrations of CGRP in CSF in the patients of cerebral vascular diseases were measured by radioimmunoassay. The results showed that CGRP concentration in CSF in the patients with ischemic cerebral vascular diseases (ICVD) was 152 +/- 60 pg/ml, which was not significantly different from the control level of 45 +/- 9 pg/ml. While the CGRP concentration in CSF in the patients with hemorrhagic cerebral vascular diseases was 3965 +/- 680 pg/ml, which was significantly higher than the levels in the control group and in the ICVD group. PMID- 1889318 TI - [Acute cerebrovascular disorders and myocardial infarction]. AB - A retrospective study in 1,314 cases with acute cerebrovascular disease was conducted. The clinical diagnosis included cerebral hemorrhage (CH) 489 cases, cerebral thrombosis (CT) 686 cases, cerebral embolism (CE) 68 cases, and subarachnoid hemorrhage (SAH) 71 cases. Of the 1,314 cases there were 21 patients (1.6%) complicated with acute myocardial infarction during the stage of stroke. The percentage of incidence was 2 cases in CH (0.4%), 13 cases in CT (1.9%), 2 cases in CE (2.9%), and 4 cases in SAH (5%). Based on the detail cases reports the incidence, death rate, diagnosis, and pathogenesis of acute cerebrovascular disease complicated with myocardial infarction were discussed respectively. PMID- 1889319 TI - [Treatment of acute cerebral infarction with PGI2--evaluating the clinical effect and observation of dynamic changes in plasma TXB2 and 6-keto PGF1 alpha levels]. AB - 18 patients with acute cerebral infarction were randomly subdivided into two groups: PGI2-treated group (11 cases) and low-molecular-weight Dextran-treated group (7 cases). Dosage of PGI2 was 2-5 ng/kg/min intravenous drip. Infusion was started within 72 hours after the onset of symptoms. The data showed that the plasma 6-keto-PGF1 alpha levels were increased, the plasma TXB2 levels, MAR as well as the scores of neurological deficit were decreased in the PGI2-treated group. The clinical improvement in PGI2-treated group is better than that in the dextran-treated group. PMID- 1889320 TI - [A random sample study of therapeutic effect of beta-receptor blocking agents in patients with subarachnoid hemorrhage]. AB - The Study on the treatment of 50 cases of subarachnoid hemorrhage (by applying beta-receptor blocking drug propranolol) and the control group of 55 cases revealed that the mortalities of the therapeutic group and the control group were respectively 4% and 9.2% (P less than 0.05) the incidences of the cerebral vasospasm were 2% and 10.6% (P less than 0.01) and those of the abnormal electrocardiograms were 6% and 21.8% (P less than 0.01). The differences between the two group were significant. The function of propranolol may be associated with the sudden increase of catecholamine after subarachnoid haemorrhage and there for the drug has the function of protection of the cardiac muscle and prevention of the cerebral vasospasm. PMID- 1889321 TI - [Effect of 654-2 on the cerebral blood flow in patients with ischemic cerebrovascular disease by measurement of 133Xe rCBF and the microcirculation of bulbar conjunctiva]. AB - Eighteen patients with cerebrovascular disorder were observed comparatively using 133Xe rCBF measurement and microcirculation test of bulbar conjunctiva before and after treatment with 654-2. Remarkable decreasing of blood flow in the brain and improving of bulbar conjunctiva microcirculation were found after treatment. We consider that the same drug caused the different change of blood flow in and out brain may due to the reaction of micrangium tissue construction, nerve regulation and different organ's micrangium to Ach. We recommend 133Xe as a objective measurement to estimate brain blood flow. The value of treatment of ischemic cerebrovascular disorder by 654-2 and raising microcirculation test as a objective measurement remains to discussed. PMID- 1889322 TI - [Clinical and CT correlative researches in deep infarction of cerebral hemispheres]. AB - Clinical and CT correlative researches in 172 patients with deep infarction of cerebral hemisphere were reported. The lesions are classified into eight types according to their location. Lateral of the central part of lateral ventricle was most frequently, and putamen, posterior limb of internal capsule, lateral of the anterior horn of lateral ventricle were subsequently. Only a few deep infarctions were watershed infarction possibly. The question of low perfusion in the peripheral of the lesion were discussed. PMID- 1889323 TI - [Pathological and etiological studies on cerebral infarction in the vertebrobasilar arterial system]. AB - 25 cases of cerebral infarcts in vertebrobasilar arterial system are reported. Those were divided into 4 groups: 1. Embolism (10), the causes were NBTE, pulmonary infarct, rheumatic or congenital heart disease, coronary artery disease, respectively, and 2 unknown. 2. Thrombosis (5), the causes were arteriosclerosis, vascular malformations in the basal part of cerebrum. 3. Inflammatory infarcts (3), those were verified from tuberculosis, syphilis and aspergillosis respectively. 4. Lacunar infarcts (7), the causes were considered from hypertension. Pathologically, it was noticed that the location of embolism often situated at the terminal of basilar artery, and that if the embolism was completely obliterated, often a hemorrhagic infarction would follow. But the thrombosis in basilar artery, even the lumen was completely obliterated, any infarct would not follow, if the related collateral circulation was satisfactory. Clinically, the embolism in basilar artery often showed sudden onset, and that the symptoms of brain stem would aggravate quickly, but the thrombosis in basilar artery, if the collateral circulation was satisfactory, and symptom of brain stem might not follow. PMID- 1889324 TI - [Beta-glucuronidase activities assay in the ischemic brain in rats]. AB - Beta-glucuronidase (beta G) being a kind of hydrolases in the lysosome, the change of beta G activities has been known to be related to the degree of the damage of tissues or cells and the permeability of the cellular membranes. This study aimed at investigating beta G activities in rat brains and their changes after incomplete brain ischemia. It was shown that the brain beta G activities increased one hour, three hours and six hours after the rat brain ischemia was produced in the experimental rat models. Especially six hours after the rat brain ischemia was effected brain oedema became markedly evident. PMID- 1889325 TI - [The relationship of hypoperfusion and dementia caused by cerebral amyloid angiopathy]. AB - The pathohistologic study was conducted on the brain of a dementia patient caused by simple cerebral amyloid angiopathy and the neural cell counts of cerebral cortices was compared with that of two normal subjects of same age. Medium to small arteries and capillaries of leptomeninges and cortices exhibited amyloid deposits. The occipital lobe was predominantly affected. 53.3% of medium to small arteries and 25.3% capillaries showed the abnormality. Decrease of neural cells also varied considerably. The occipital lobe was involved most severely and 54.8% neural cells lost in this lobe. The increase of amyloid deposits was closely related to the severity of ischemic lesion and loss of neurons. The findings in this patient indicated that the pathogenesis of dementia caused by cerebral amyloid angiopathy might be more complicated. The possible mechanism might be that the deposition of amyloid destroyed the structure of cerebral vasculature and lead to the impairment of autoregulation. These pathologic changes resulted in hypoperfusion which caused ischemic changes and loss of neurons and dementia. PMID- 1889326 TI - [Auditory event-related potentials in Parkinson's disease]. AB - The results of event-related potential (ERP) components were studied in 25 cases of Parkinson's disease. This study included 33 normal volunteers (14 females and 19 males). With no prior history of neurologic or psychiatric illness. They were all over 50 years of age in "Auditory oddball" event-related potential paradigm. All of the Patients (20 males and 5 females) were 45-80 year's old. The latencies of the patients on N2P3aP3b wave which reflected cognitive process (activity) were significantly prolonged (P less than 0.001, P less than 0.001, P less than 0.02). The amplitude of P3a, P3b wave were decreased (P less than 0.001). This cognitive function were markedly different from normal. It's valuable in the diagnosis and follow up of Parkinson's disease. The origin of waves of ERP components and clinical application were also discussed in this paper. PMID- 1889327 TI - [Auto-cholinergic synapse dysfunction in patients with generalized epileptic seizures. A preliminary report]. AB - The mechanism of epileptic seizures so far remains unclear. Immunological disturbances may be one of the possible mechanisms. The assumption that primary epilepsy is an autoimmune disease lacks an experimental basis. In order to search any relationship between generalized epileptic seizures and autoimmune we examined and measured the serum anti-acetylcholine receptor antibody (A AchR Ab) and anti-synaptic premembrane antibody (A PrM Ab) in 12 patients with typical absences, 20 patients with generalized tonic-clonic seizures (GTC) and 6 patients with Lennox-Gastaut Syndrome. 2 (16.7%) out of 12 patients with absences showed positive both A AchR Ab and A PrM Ab, positive A AchR Ab in 1 patient. Among 20 patients with GTC both A AchR Ab and A PrM Ab were positive in 7 patients (35%), A PrM Ab was positive in 1 patient. Totally in 8 patients A PrM Ab was positive. However, the difference between the two Antibodies was not significant (1.1:1). The two kinds of antibody were positive in 5 (83%) out of 6 patients and A PrM Ab was positive, but A AchR Ab was doubtful in another one patient with Lennox Gastaut syndrome. Therefore, all the patients with Lennox-Gastaut syndrome showed positive antibody. Our data suggested that different types of generalized epileptic-seizures showed different severity of autoimmune dysfunction. The meaning of this kind of immune dysfunction needs further investigation. PMID- 1889328 TI - [A family of Fahr's disease]. AB - A family of Fahr's disease with autosomal dominant inheritance was reported 5 cases in 3 generations were affected in this family. The first patient was admitted for operation because of intracranial hematoma. No specific abnormality was found in the patients except intellectual impairment CT, however, revealed high density lesions in basal ganglion cerebellum, and cerebral white matter. PMID- 1889329 TI - [A study on the serum biochemistry in carrier detection of Duchenne muscular dystrophy]. AB - The serum levels of creatine kinase, creatine kinase isoenzyme (MB), lactate dehydrogenase, pyruvate kinase and myoglobin were studied in 85 carriers of Duchenne muscular dystrophy and 125 normal female controls. The results showed that the best single test for carrier detection was myoglobin or creatine kinase, the combination of multiple tests could increase the effectiveness of carrier detection, in which the best and most rational tests to use in combination were creatine kinase, lactate dehydrogenase and myoglobin. PMID- 1889330 TI - [Acetylcholine receptor antibody titer, sensitivity to curare electromyogram and disease severity in myasthenia gravis]. AB - All of 39 rabbits immunized with acetylcholine receptors invariably formed anti AChR Abs and some of them developed muscular weakness or flaccid paralysis. Pharmacological, physiological and ultrastructural studies indicated that the pathology of experimental autoimmune myasthenia gravis in rabbits resembled that of human myasthenia gravis. The titer of anti-AChR Abs correlated poorly with disease severity and did not simply predicted the muscular weakness. The results ruled out the possibility that antigenic modulation of AChR was sufficient to account for the induction of myasthenia gravis. There was a close relationship between the sensitivity to curare and disease severity, but only part of immunized animals appeared electromyogram change. This led us to conclude that serum anti-AChR concentration would not be the single pathological factor in myasthenia gravis and disease severity may correlate with amount of normal AChR. PMID- 1889331 TI - [Determination of praziquantel levels in cerebrospinal fluid and plasma in patients with cysticercosis of the central nervous system treated with praziquantel]. AB - The CSF and plasma concentrations of praziquantel (PZQ) were determined with high pressure liquid chromatography in 37 patients with cysticercosis of the central nervous system during a dosing regimen of PZQ 20 mg/kg p o q 8h for 3 days. The pharmacokinetic parameters were estimated using the nonlinear least squares method. The results showed that PZQ could pass through the blood-brain barrier. The absorption and elimination rates in CSF were slower than those in plasma, the corresponding mean levels being 0.1 and 0.27 micrograms/ml, which were lower than those in plasma. There was a linear correlation between CSF and plasma concentrations (r = 0.87, P less than 0.01). The neurological complications during the period of therapy were not related to the CSF level of PZQ. The cure rates of muscular and cerebral cysticerci were 14/14 and 5/37 respectively. The difference in susceptibility was considered to be caused by the pharmacokinetic behavior of PZQ and CSF and plasma. It was suggested that in general favorable regimens had better be adjusted with adequate increase of the dosage of PZQ, shortening the dosing interval, and prolong the period of PZQ treatment, but individualization of the PZQ dosing regiment would be necessary in accordance with the plasma concentration of the PZQ. PMID- 1889332 TI - [Event-related potential P300 in cerebral infarction]. AB - N1, P2 and P300 potentials were studied in 20 cases of cerebral infarction and 47 healthy controls with standard technique of auditory event-related potentials. Healthy controls of both sexes, different ages, education levels and cognitive capacity did not show apparent differences in the latency of p300 (P greater than 0.05, respectively). The patient group, however, revealed significant (P less than 0.001) prolongation of latency of P300 (mean = 409.6 +/- 50 ms) as compared with 28 well matched healthy subjects (mean = 337.7 +/- 24 ms). Although there was some decline of amplitude of P300 in the patient group, the difference between the control and patient groups was not significant (P greater than 0.05). There was significant difference in the Cognitive Capacity Screening Examination findings between the control and patient groups (P less than 0.01), but it seemed that the evaluation of latency of cognition-related p300 might be more objective and sensitive (P less than 0.001). PMID- 1889333 TI - [Establishment of a murine ascites hepatoma cell line H 22-F 25/L and its biological characteristics]. AB - Having been passed for 160 generations, a cell line designated as H 22-F 25/L was established from a murine tumor lymphatic metastatic model H 22-F 25 which had been set up in our college. The cell line was in suspension culture with a rapid proliferation and stable growth. The peak time of cell division and proliferation was 48 and 96 hours after culture. In a week, the cell number was increased by 25 times. H 22-F25/L still keeps the features of a poorly differentiated cancer. Its tumor inducing rate (in vivo) was 100% in 615 mice. Lymph node metastasis rate was 50% and pulmonary metastasis rate 10%. H 22-F 25/L is a population of heterogenetic tumor cells including 2 stem cell lines (the model number of chromosomes being 43 in 40% tumor cells and 86 in 32%) and some side lines. The common marker chromosomes M1, M2, M3 and M4 were present in all stem and side lines. PMID- 1889334 TI - [Invasion of human lung adenocarcinoma cell line LTEP-a2 into various organs of different species]. AB - The invasiveness of human lung adenocarcinoma cell line LTEP-a2 was investigated in co-culture system of tumor cells and fragments of the heart and liver from the newborn, rabbit and rat. It was found that the tumor cells had different invasive behaviors, for example cell diastrophism, proliferation or invasion speed and adenic formation when invading various species or various organs in the same species. When invading the fragments of newborn heart and liver, strong cell diastrophism potential, cell twist or formation of multiprocess pseudopodia and mitosis could be observed. The result was contrary to the above when the fragments of rat heart and liver were used as the target. When the fragments of rabbit liver were invaded, marked adenization was formed by cancer cells with the invading speed increased. However, the adenic structure was absent as the heart fragments of rabbit were invaded. The results indicate that target organs could change biological behavior of the invading tumor cells to different degrees even their differentiation. It may be related to structure and biochemical property of the target organs. PMID- 1889335 TI - [Estrogen and progesterone receptors in esophageal carcinoma cells]. AB - Distribution of estrogen and progesterone receptors (ER and PR) was studied in esophageal tissue (48 patients with esophageal carcinoma, 20 normal subjects and 12 fetuses) and Eca 109 cell line using enzyme-linking affinity immunohistochemistry method. In the meantime, plasma estradiol and progesterone levels were determined in 8 patients with esophageal carcinoma using radioimmunoassay method. The results showed that the positive rates of ER and PR in esophageal carcinoma were 43.75% (21/48) and 39.58% (19/48). Both ER and PR were positive in Eca 109 cell line whereas they were negative in the control groups. Sex and grade of cancer were the factors influencing the positive rates of ER and PR. It is indicated that carcinogenesis of esophageal carcinoma might be related to sex hormone metabolism. The measurement of ER and PR may be useful in clinical practice. PMID- 1889336 TI - [Retinoic acid and 12-0-tetradecanoylphorbol-13-acetate (TPA) inducing bipotent differentiation of cultured primary bone marrow cells from leukemia patients]. AB - The in vitro differentiation of cultured primary bone marrow cells from patients with acute promyelocytic leukemia (M3) and chronic myelocytic leukemia (CML) induced by retinoic acid (RA) and TPA was studied. The results indicated that both the M3 and CML bone marrow cells bipotently differentiated into either myeloid or macrophage-monocytic lineage in response to the inducers. On M3 cells the effect of TPA was more potent than RA, and TPA could inhibit the phenotype of myeloid terminal differentiation induced by RA but not vice versa. However, RA could overcome the TPA-induced inhibition of myeloid terminal differentiation of CML cells. These experiments provide a useful model for studying the molecular mechanism of hematopoietic cell differentiation. PMID- 1889337 TI - [Value of gastroscopy in postoperative patients with gastric cancer]. AB - From September 1980 to May 1987, fiberoptic gastroscopy was performed in 3538 patients. Of them, 356 (10%) had received operation for gastric cancer. A second primary cancer was found in 31 cases, recurrent gastric cancer in 18 and adenoma in 87. Among the 138 asymptomatic operated patients, a second primary cancer developed in 8, and 6 of them were in the early stage. In the 218 symptomatic operated patients, a second primary cancer developed in 23, and 10 of them were in the early stage. The results suggest that gastroscopic examinations at regular intervals are mandatory for asymptomatic postoperative patients. PMID- 1889338 TI - [Image diagnosis of small renal carcinoma--a report of 7 cases]. AB - Seven cases (8 tumors) of small renal carcinoma (less than 3 cm in diameter) proven by pathology were reviewed. It accounted for 7% of patients with renal cell carcinoma during the same period. Sonogram was hypoechogenic in 3 tumors, isoechogenic in 2 and slightly hyperechogenic in 3. Heteroechogenicity was shown in 3 cases and homoechogenicity in 5. None of the margins was sharp. CT scan showed 4 isodense, 1 hypodense and 1 slightly hyperdense masses. After contrast enhancement, increased attenuation to different degrees but still lower than the normal renal parenchyma was observed. The sensitivity of IVP was low because of the small size of the tumor, peripheral location and rare involvement of the renal calyces and pelvis. MRI is helpful in differential diagnosis of hilar adenopathy and small vessels for tumor staging. Yet, the value of MRI for renal masses should be further studied. On cost benefit, sonography and CT are more practical in the diagnosis of renal carcinoma. PMID- 1889339 TI - [Combination treatment of acute non-lymphocytic leukemia with HOAP and AA- preliminary report of 14 cases]. AB - Fourteen patients with acute non-lymphocytic leukemia (ANLL) were alternately treated with HOAP (harritonine, oncovin, Ara-C and prednisone) and AA (adriamycin and Ara-C). The complete response rate was 64.3% (9/14). Four in 5 previously untreated patients and 5 in 9 patients with relapse achieved complete response. The side effects were weakness, gastrointestinal disturbance, bone marrow suppression and pancytopenia, which lasted for 2-3 weeks after discontinuation of treatment. Sinus tachycardia was noted in 3 cases and inverted T wave in 2. The authors consider that this may be a treatment of choice in ANLL because of its high response rate, shorter attainment to complete remission and mild side effects. But the long term results still need to be studied. PMID- 1889340 TI - [Preliminary experience in salvage treatment for advanced recurrent cancers of the head and neck]. AB - Sixteen patients with far advanced recurrent malignancies (later than Stage IV) of the head and neck were treated with radical salvage surgery combined with radiotherapy, chemotherapy, immunotherapy, laser and/or traditional Chinese medicine. The 2- and 3- year survival rates were 56.3% (9/16) and 37.5% (6/16), which were superior to 6.3% (1/16) and 6.3% (1/16) of similar patients who refused treatment. The authors are of the opinion that aggressive treatment should be attempted for patients with far advanced recurrent cancers of the head and neck. PMID- 1889341 TI - [Dihydroetorphine hydrochloride for moderate and severe cancer pain]. AB - One hundred and three patients with moderate and severe cancer pain were given a sublingual analgesic agent--dihydroetorphine hydrochloride (DHE). Relief of cancer pain was moderate or complete in 89.3% (92/103). The average relief time (ART) was 3.9 hours and the average time before effectiveness was 20 minutes. In patients with acute or chronic cancer pain, moderate and complete pain-relief rates were 91.3% and 82.2% (P = 0.237). Difference of ART between them was insignificant (P = 0.299). The main clinical side-effects were somnolence (60%), dizziness (72%), nausea (30%), vomiting (16.5%), constipation (5%) and shortness of breath (8%). In two of the patients, the administration of DHE had to be stopped due to its side-effects. Age, sex and site of cancer pain were not related to the analgesic effects of DHE, but the pain-relief in patients with bladder cancer was poor (P less than 0.001). Within certain range, increase in dose was able to enhance its analgesic effect (P less than 0.001) and reduce drug resistance (P less than 0.001). PMID- 1889342 TI - [Clinical analysis of 25 cases of multiple myeloma]. AB - Since 1972, 25 cases of multiple myeloma had been diagnosed. Of them, 22 (88%) were over 50 years old. Most of them had bone pain with anemia to different degrees. Marked elevation of ESR was found in 19 cases. Bence-Jones protein was detected in the urine in 15 cases resulting in elevation of blood urea nitrogen and creatinine. Twenty-two of 23 cases were found to have a high peak of abnormal globulin. Increased plasma cells with abnormal features in the bone marrow were observed in 17/21 cases. Multiple osteolytic lesions, compression fracture and osteoporosis on X-ray films were shown in the majority. Of these 25 cases, 10 had advanced myeloma. These 10 patients all died during admission and eight without any chemotherapy. In the other 15 cases treated with chemotherapy, marked response was seen in 1, partial response in 8 and no response in 6. The diagnosis of the disease is discussed in detail. PMID- 1889343 TI - [Electrocardiogram analysis of adriamycin cardiotoxicity in 160 cases]. AB - From January 1986 to May 1989, 160 cancer patients proven by pathology were treated by combined chemotherapy with adriamycin (ADM) as the chief agent. Of them, 20 were given simultaneous cyclophosphamide (CTX) and 14 had received mediastinal irradiation. 40 mg/m2 of ADM was given by rapid IV bolus injection which was repeated every 3 weeks. All but 9 had normal electrocardiogram (ECG) before ADM administration. In these 9 patients, when ADM reached certain accumulated dose, ECG showed no further changes. Thirty-seven (24.5%) cases had various types of abnormal ECG, manifested as arrhythmia in 11, non-specific ST-T changes in 12 and low voltage in 14. Of these 37 patients, fatal congestive heart failure developed in 4 cases. To reduce ADM cardiotoxicity, its indication should be strictly adhered to; ADM may be divided to two fractions on Day 1 and 2, for those patients receiving simultaneous CTX or who had had mediastinal irradiation, ADM accumulated dose should be limited to 400 mg/m2; ADM should never be given to patients with lowered QRS voltage greater than or equal to 30% of the normal value or with obvious ST-T changes; the accumulated doses should range from 450 to 550 mg/m2, simultaneous anti-histamines, anti-adrenaline, coenzyme Q10 and vitamin E are indicated. PMID- 1889344 TI - Relationship between erythrocyte sorbitol content and diabetic microangiopathy in patients with non-insulin-dependent diabetes mellitus: the study of a diet loading test. AB - To determine whether erythrocyte sorbitol content could become an indicator of diabetic microangiopathy, we studied the relationship between the changes in erythrocyte sorbitol content in response to diet loading and diabetic microangiopathy in patients with non-insulin-dependent diabetes mellitus. The increase of change in erythrocyte sorbitol content (delta Sor) after diet loading (420 kcal) significantly correlated with that of plasma glucose levels (delta BS). The patients with less than or equal to 40 m/s of motor or sensory nerve conduction velocity (MCV and SCV) had significantly higher delta Sor and delta Sor/delta BS values than those with greater than 40 m/s of MCV and SCV; nevertheless, there were no significant differences in delta BS between the two groups. Furthermore there was a significant negative correlation between nerve conduction velocity and delta Sor and Delta Sor/delta BS values. On the other hand, the patients with nephropathy or retinopathy showed no significant increase in delta Sor or delta Sor/delta BS compared with patients without these complications. The results demonstrated that delta Sor and delta Sor/delta BS could become indicators of the presence or severity of diabetic neuropathy. Furthermore the more significant participation of alteration in the polyol pathway in the pathogenesis of neuropathy than of the other microangiopathies was suggested. PMID- 1889345 TI - Renal handling of glycated albumin in non-insulin-dependent diabetes mellitus with nephropathy. AB - Renal handling of glycated albumin in diabetic nephropathy was examined by studies on renal selectivity for glycated albumin in 23 normal controls and 52 patients with non-insulin-dependent diabetes mellitus (NIDDM) with various degrees of nephropathy. The serum and urinary levels of glycated albumin were measured by enzyme-immunoassay with monoclonal antibody to glucitol-lysine residues in human glycated albumin. The diabetic patients were divided into 3 groups according to the albumin index (AI): patients with normoalbuminuria [AI less than or equal to 30 mg/g creatinine(Cr)], with microalbuminuria (30 less than AI less than or equal to 270 mg/g Cr), and with macroalbuminuria (AI greater than 270 mg/g Cr). The renal selectivity for glycated albumin was calculated from the ratio of the urinary to serum level of glycated albumin. In the controls, the renal selectivity was as high as 4.40 +/- 0.48, and significantly higher than those in patients with normo- (2.87 +/- 0.29), micro- (1.72 +/- 0.20) and macroalbuminuria (1.26 +/- 0.23). The renal selectivity was inversely correlated with the AI in diabetic patients (r = -0.58, P less than 0.01). These data indicate that glycated albumin was selectively excreted in the urine and that the renal selectivity in diabetic patients gradually decreased to a value of 1 with increase in albuminuria. When the patients with normoalbuminuria were divided into two subgroups with high and low albumin excretion, the renal selectivities for glycated albumin in both subgroups were still significantly lower than that in controls. These results suggested that early diabetic nephropathy which cannot be detected clinically by albuminuria can be diagnosed by measurement of renal selectivity for glycated albumin. PMID- 1889346 TI - Correlation of insulin deficiency and hypertriglyceridemia in diabetic rats. AB - The relationship between plasma insulin (IRI) and lipid concentration, or triglyceride (TG) kinetics was studied in streptozotocin-induced diabetic rats (DM) to examine how insulin deficiency is associated with the mechanism of hypertriglyceridemia (HTG) in diabetes. Plasma glucose and ketones were significantly elevated and IRI reduced in DM. Plasma glucagon concentration in DM was similar to controls. The plasma concentration of TG, total cholesterol phospholipid and apoprotein B was 3-4-fold higher in DM compared to control rats. The HTG in DM was mainly attributable to an increase in the concentration of TG rich lipoprotein (TRL). Multiple linear regression analysis showed a positive relationship between the concentration of non-esterified fatty acid and plasma lipids, but the decrease in IRI best correlated with increased concentrations of lipids and apoprotein B in plasma and TRL. Neither glucose nor glucagon correlated significantly with lipids or apoprotein B concentration in plasma or TRL. The rate of entry of TG into blood was similar between DM and controls, and in DM this significantly correlated with IRI. Clearance of radiolabeled TRL-TG in DM was significantly decreased and correlated with IRI. Conversely, the removal of radiolabeled Intralipid-TG was similar for DM and controls. The data suggest that insulin critically regulates TRL-TG metabolism in DM and that a catabolic defect of TRL-TG due to insulin deficiency is a main reason for the HTG.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1889347 TI - Prediction of persistent carbohydrate intolerance in patients with gestational diabetes. AB - A 12-month prospective study was carried out in 120 Chinese patients with gestational diabetes who were found to have persistent carbohydrate intolerance at 6 weeks postpartum. The 75 g OGTT and WHO diagnostic criteria were employed for both antepartum and postpartum assessment. By 12 months, persistent carbohydrate intolerance was found in 13.3% of the patients only, 6 patients were diabetic while 10 had impaired glucose tolerance. Of those whose carbohydrate tolerance reverted to normal, 85% did so within the first 6 months. The clinical variables were analysed by multiple discriminant analysis using the logistic model. Five prognostic variables which were predictive of persistent carbohydrate intolerance at 12 months were identified. In order of decreasing predictive value, these included a high fasting glucose during pregnancy and at the first postnatal visit, a high antepartum 2 h blood glucose, the requirement of insulin during pregnancy, and a high postpartum 2 h blood glucose. Macrosomia, gestational age at diagnosis and a family history of diabetes were not predictive of persistent carbohydrate intolerance. Multiparity, maternal age and body mass index were of marginal significance only. The fitted logistic model provides a mechanism to estimate the probability of persistent carbohydrate intolerance. Such information will be helpful in patient counselling and in the efficient planning of postpartum medical follow-up. PMID- 1889348 TI - Use of human ultralente as the basal insulin component in treatment of patients with IDDM. AB - To determine the suitability of a single subcutaneous evening injection of human ultralente (UL) as the basal component of an intensive insulin therapy program, insulin concentrations were measured in five insulin-dependent diabetic volunteers over a 40-h period. Each patient had been maintained on a human UL based program for at least one month prior to the study. All short-acting insulin was withheld during the study. The onset of action of human UL was 2 to 4 h, and a broad, variable peak was observed between 6 and 12 h after each injection. We concluded that human UL does not provide constant basal insulin concentrations. When human UL is considered as part of an intensive insulin therapy program, this potential disadvantage must be weighed against the potential advantage of low antigenicity. PMID- 1889349 TI - Taste impairment for glucose in diabetic PTC tasters and non-tasters. AB - Effect of high blood glucose levels in diabetes mellitus was studied on gustatory responses to glucose in PTC tasters and non-tasters, before and after the ingestion of a glucose solution. After a 12-h overnight fast, prescreening for phenylthiocarbamide (PTC) sensitivity was done in each subject, and then each subject tasted, and rated, 7 concentrations of glucose solutions for intensity and hedonic responses. Blood glucose levels were also determined under fasting and then after a 100-g glucose load. A decrease in palatability of the glucose solutions induced by the glucose load (negative alliaesthesia) was evident in both groups of subjects. Tasters showed higher hedonic ratings (Mean 4-25), as compared to non-tasters (Mean 3-70) and this difference was more evident after the glucose load in non-tasters. PMID- 1889350 TI - Prevalence, age at diagnosis, clinical characteristics and treatment of diabetes in the young in Pahang, Malaysia. AB - The prevalence, age at diagnosis, clinical characteristics and treatment of young diabetics, younger than 40 years were determined on the basis of a cross sectional study of medical records of 2 health districts in Pahang, Malaysia. There were only 20 insulin-dependent diabetics (IDDM), prevalence 0.07 per 1000 inhabitants. There were 84 non-insulin-dependent diabetics (NIDDM), prevalence 0.3 per 1000 inhabitants. Three of the NIDDM patients could have malnutrition related diabetes. Many NIDDM patients were asymptomatic which is an important reason why many of them remain undetected in the community. Seventy-four percent of the patients below the age of 30 years at diagnosis had NIDDM, 56% of the patients below the age of 20 years at diagnosis also had NIDDM and 54% of the NIDDM patients had a strong family history of diabetes. Many NIDDM patients were misdiagnosed as IDDM, especially if they were underweight, leading to considerable overuse of insulin. This study confirms that IDDM is rare in Malaysia, as in other Asian countries. Most young diabetics have NIDDM and have a strong family history. This pattern of diabetes in the young is unlike that seen in the West. PMID- 1889351 TI - The prevalence of diabetes mellitus in the adult population of Guadeloupe as estimated by history or fasting hyperglycemia. AB - A study was conducted between January 1984 and March 1985 to determine the prevalence of diabetes in the adult population of Guadeloupe (18 years of age and over). A two-step sampling frame, using a sampling fraction of 0.46%, where the primary units were composed of districts and where sub-units were households, was used. The household refusal rate was 22%. Subjects were classified as 'diabetic' when they were either already known or when their fasting plasma glucose was above 8.0 mmol/l. The total age and sex standardized prevalence of diabetes among the adult population of Guadeloupe can be estimated at 6.6%. The high prevalence rate appears to be related to obesity (strongly in women), a genetic susceptibility (22.5% of age standardized prevalence among subjects of Asian Indian origin for both sexes), and, possibly, in men of African origin only, to a maternal history of diabetes. PMID- 1889352 TI - [Splenic cysts. Their morphology, diagnosis and therapy]. AB - Over a 10-year period, nine patients (four men, five women, mean age 27 years) underwent surgery for splenic cysts (six epidermoid cysts, two mesothelial cysts and one pseudocyst). Six patients had had suggestive clinical symptoms, but, in the other three, the cysts were only discovered by chance on ultrasound scan. Three of the patients with epidermoid cysts had raised serum concentrations of the tumour markers carcinoembryonic antigen (CEA) or carbohydrate antigen (CA 19 9. All six benign epidermoid cysts contained immunohistochemically demonstrable CEA and/or CA 19-9 in the inner epithelial layer, implying a mesothelial origin for these cysts. In five cases the splenic cysts were completely extirpated (splenectomy in two, hemisplenectomy in one, enucleation in two); in four cases cyst resection was performed, leaving part of the cyst adherent to the spleen. In one of these four patients, a 4 cm cyst persisted postoperatively in the hilus of the spleen, but has remained unchanged over an 8-year period. Splenic cysts are usually benign, despite the presence of tumour markers in the cyst wall, and do not require removal. The only indications for surgical intervention are complications (e.g. rupture), symptomatic cysts or asymptomatic cysts with an increased risk of rupture (diameter greater than 5 cm). The very rare parasitic and infective forms must always be surgically sterilized. PMID- 1889353 TI - [The duplex sonographic diagnosis of portal hypertension in liver cirrhosis. The effect of a standardized test meal on portal hemodynamics]. AB - The effect of a standardized test meal on portal haemodynamics was measured by duplex ultrasonography in healthy subjects (12 men and 13 women; mean age 43 +/- 9 years) and patients with liver cirrhosis (14 men and 11 women; mean age 55 +/- 10 years). Maximal flow velocity, vessel diameter and flow volume were measured in the portal vein and superior mesenteric artery before the test meal and 15, 30 and 45 min thereafter. After a 12-hour fasting period maximal flow velocity in the portal vein was significantly lower in the cirrhosis patients than the normal subjects (P less than 0.05), but the individual values clearly overlapped. 30 min after the test meal flow velocity in the portal vein rose by 22%, flow volume by 29% in the cirrhosis patients, but by 76% and 131%, respectively, in the normal controls (P less than 0.01). Vessel diameter remained constant in the patients, but increased significantly in the controls (P less than 0.05). There was no overlapping of values between the two groups. The increase in flow velocity in the superior mesenteric artery was nearly the same in both groups. It is concluded that, after a test meal the haemodynamic differences between normal subjects and cirrhosis patients becomes quite marked and thus can provide a more exact diagnosis of portal hypertension by duplex ultrasonography. PMID- 1889354 TI - [The leukostasis syndrome with a cerebral infarct in rapidly progressing chronic lymphatic leukemia]. AB - An 82-year-old woman developed acute neuropsychiatric signs (confusion, disorders of speech and vision) together with ataxic gait and left hemiparesis mainly affecting the lower limb. For 10 years she had been known to have chronic lymphatic leukaemia (CLL) which had not hitherto needed treatment. The patient had an exceptionally high leucocyte count (1,300,000/microliters), most of the cells being morphologically atypical lymphocytes. The computed tomogram of the skull showed a marginal zone infarct with a hypodense focus in the area of the right middle and posterior cerebral arteries, extending from the cortical to subcortical zones almost as far as the posterior horn. This was interpreted as a leukostasis syndrome with cerebral infarction due to rapid progression of the CLL. Significant reduction of leucocyte count with considerable improvement in clinical signs was achieved after three doses of vincristine and prednisone together with one cycle of COP (cyclophosphamide, vincristine, prednisone) therapy. Although the leucocyte count is not an important criterion in planning the therapy of CLL, in the event of rapidly increasing leucocytosis it is important to begin cytoreductive treatment in good time so as to avert the leukostasis syndrome. PMID- 1889355 TI - [Lipomatous hypertrophy of the atrial septum. Cardiac-induced syncope in hamartoma of the right heart atrium]. AB - A previously well 40-year-old woman suddenly collapsed and had to be resuscitated by an emergency physician. Admitted to hospital she remained unconscious and needed artificial respiration. Diagnostic tests failed to find evidence for pulmonary embolism, myocardial infarction or myocarditis. ECG monitoring in the intensive care unit merely revealed occasional unifocal ventricular premature systoles. Echocardiography was within normal limits. She remained in coma without spontaneous respiration. Cranial computed tomography and serial electroencephalograms indicated brain death. Autopsy revealed lipomatous hypertrophy (hamartoma) of the atrial septum with extensive bleeding into it as the most likely cause of (unrecorded) malignant cardiac arrhythmias. PMID- 1889356 TI - [The leukostasis syndrome]. PMID- 1889357 TI - [Erythropoietin substitution in anemic patients with rheumatoid arthritis?]. PMID- 1889358 TI - [The intensive medical treatment of severe malaria tropica]. PMID- 1889359 TI - [ST-segment depression in the exercise ECG]. PMID- 1889360 TI - [The surgical treatment of symptomatic carotid stenosis. An interim analysis of the European Carotid Surgery Trial]. PMID- 1889361 TI - [The effect of metabolic alkalosis on colostrum and milk quality of cows and on the health status of their newborns]. AB - The investigation was carried out on 12 cows and their calves. At the time of 3 months before parturition and 7 days after parturition metabolic alkalosis one provoked with the high protein feed. The laboratory investigations dependent of determinations on the rumen content the pH, NH3, volatile fatty, acids, the protozoa, bacteria, total gas CO2 and CH4. On the arterial and venous blood on determination the pH, BE, sO2, pO2, HCO3 and coefficient of consumption of the oxygen, and on the venous blood the levels of Na, K, Mg, Ca, P, total proteins, albumins and globulins, cholesterol, glucose, bilirubin, alkaline phosphatase and urea. In the colostrum and in milk one determined the pH, potential acidosis- degree SH, proper weight, proteins, dried mas of milk, time of coagulation in the presence of rennin, Na, K, Ca, Cl, total fats and their composition with different fatty acids. No existed truly changes of clinical signs, only feces was sickly. The metabolic alkalosis of cows decreased the consumption of oxygen across the tissue, deficient of the energy, disorders of water-electrolyte and acid-base balances. The calves form cows with metabolic alkalosis delivered also with metabolic alkalosis, with the symptoms of achondroplasia and degeneration of the liver and other organs. Metabolic alkalosis of cows influenced on the quality of colostrum and milk. The colostrum gained from cows with alkalosis caused of disturbance of gastrointestinal tract and diarrhea presence. PMID- 1889362 TI - Influence of sodium taurocholate on the potency and duration of action of some neuromuscular blocking agents. AB - The effect of sodium taurocholate (S. T.) on the contractile response of rat phrenic nerve diaphragm, frog's musculus rectus abdominis and frog's musculus gastrocnemius sciatic nerve preparation was studied. Moreover, interaction of S. T. with neuromuscular blockers are carried out, too. S. T. was found to have a dose-dependent reduction in the contractile response of the tested preparation. On the other hand, the inhibitory effect induced by S. T. did not block or alter the stimulatory effect of either acetylcholine or prostigmine. Trials were made to estimate the potency of S. T. in a comparison with other skeletal muscle relaxant drugs. In this respect S. T. exhibited a more potent effect than gallamine. In contrast, other skeletal muscle relaxants (dtubocurarine, atracurium, pancuronium and succinylcholine) were highly potent. There was also a marked synergistic effect between S. T. and other neuromuscular agents. PMID- 1889363 TI - [The distaff philosophy in folk medicine animal science]. AB - Spinning, distaffs and spinning-rooms are used to be closely linked with superstitious thinking and behavior. The so-called distaff philosophy reflects the wisdom of the old black magic spinners. Their wisdom was known by the popular veterinary medicine. With the help of the collections of distaff philosophical thoughts the relation between distaff philosophy and popular veterinary medicine is shown. PMID- 1889364 TI - [The hypophysis of Monodelphis domestica (Marsupialia): the state of organ development and cell differentiation in the adenohypophysis on different days post partum]. AB - In the newborn gray short-tailed opossum, Monodelphis domestica, the fusion of the neurohypophysis and adenohypophysis has not finished. A compression of the adenohypophyseal vesicle is exerted by the neurohypophysis. The latter, as can be seen in a 12-day old specimen, finally, will be almost completely wrapped into the adenohypophysis. The adenohypophysis of the newborn and early pouch-young shows substantial growing on the basis of mitoses mainly in the pars intermedia, but in the pars distalis, too. Cytodifferentiation in the newborn, light microscopically, is indicated by an increasing heterogeneity of cell morphology which is most obvious in the cranial and caudal regions of the median sections. Electron microscopically, the presence of small quantities of granules as well as small quantities of golgi membranes and ribosomal endoplasmic reticulum, respectively, gives evidence of a beginning synthesis activity in the newborn. PMID- 1889365 TI - [Endogenous opioid peptides in cattle during pregnancy, birth and the newborn period]. AB - The concentrations of beta-endorphin and met-enkephalin in plasma were investigated in cows in different stages of gestation, during parturition and in the early postpartum period as well as in their newborn calves. Plasma beta endorphin concentrations were low in the early stages of pregnancy. In the last month of gestation beta-endorphin levels almost as high as during parturition were found. Therefore in cattle the antepartum increase in plasma beta-endorphin concentration is not linked to the onset of labour. Met-enkephalin levels in plasma of calving cows were higher than those in cows in the last month of gestation. For met-enkephalin a relation to the stress of parturition is more likely than for beta-endorphin. In conjunction with a cesarean section the concentrations of beta-endorphin and met-enkephalin in plasma increased during surgery. This increase is likely to be caused by surgery-related stress. Calves showed highest beta-endorphin concentrations immediately after delivery. One hour post natum beta-endorphin levels were markedly decreased and showed only minor changes thereafter. In calves born at term highest met-enkephalin concentrations were found immediately post natum with levels decreasing continuously over the first two days of life. Preterm calves showed lower met-enkephalin concentrations in plasma than those born at term. During the first hour post natum in preterm animals met-enkephalin levels in plasma even increased. A highly significant correlation existed between met-enkephalin levels and the degree of acidosis in calves. An antagonism between endogenous opioids and catecholamines in newborns is suggested. PMID- 1889366 TI - [Epidemiological studies of the infection of ticks with borreliosis agents in small mammals from north Germany]. AB - In a two years study into the infestation of ticks with Borrelia burgdorferi from mice in North Germany 1330 mice out of 11 species could be examined. Altogether 508 mice showed to be parasitized by 1445 ticks belonging to three species of Ixodes. 777 I. ricinus from 334 mice could be tested for B. burgdorferi. In 66 ticks (8.5%) from 34 mice (10.2%) borreliae could be demonstrated. These discoveries came from 9 of 14 investigated forest regions in Lower Saxony. PMID- 1889367 TI - [A phagocytosis test for the evaluation of the local immunity status during endometritis therapy with special regard to the use of uterofertil in cattle]. AB - After the influence of organic acids or peroxide acids with low concentration upon mucous membranes results a higher activity of the topical defence-situation. The application of a 0.2 per cent solution of peroxyethane acid (drug Uterofertil) into the uterus for endometritis-therapy directs an increase of phagocytosis-activity not only topical but also in the peripheric circulation of blood. The phagocytosis-activity was measured with a test by granulocytes. Other drugs were also tested, which will needed by endometritis-treatment of cattle. PMID- 1889368 TI - [The nature of the dog--a contribution to the keeping and breeding of so-called fighting dogs]. AB - The behavioural repertoire of dogs derives from that of the wolf. But there are distinct race-specific differences which go back to the man's breeding influence in the course of domestication to develop special qualities in dogs. Today, dog keeping no longer corresponds to these qualities of dogs in many ways. We refer to the problems resulting from this and man's responsibility for the establishment of a man-dog relationship that is functional and responds to the dog's character. The abuse of certain dog behaviour by man has to be pursued consistently. In the same way we must also take care of an unforced integration of dogs into our society. PMID- 1889369 TI - [The phosphoenolpyruvate content of milk as an indicator of the energy balance of the dairy cow (short communication)]. PMID- 1889370 TI - Effects of subacute pretreatment with carbamate together with acute adjunct pretreatment against nerve agent exposure. AB - Visual observations were made to compare the pretreatment benefits of subacute (75 micrograms/hr, sc) and acute (146 micrograms/kg, im, at 30 min) deliveries of physostigmine salicylate (Phy) against 2 or 5 LD50s (60 or 150 micrograms/kg, sc) of soman in guinea pigs; scopolamine, 80 micrograms/kg, im, was given routinely at 30 min. In a second set of studies, pretreatment with subacute carbamate [sc, Phy 36 micrograms/hr or pyridostigmine (Pyr), 50 micrograms/hr] and acute adjunct (im, scopolamine, 0.48 mg/kg, or trihexyphenidyl, 2 mg/kg) at 30 min, was used against soman (5 LD50s, sc) and VX (18.4 micrograms/kg, sc; 2 LD50s); atropine (16 mg/kg, im) and 2-PAM (25 mg/kg, im) were given at 1 min post soman. In all studies, lethality, % convulsing, convulsive/subconvulsive score, and recovery time were noted. Subacute dosing for 7 days was done via 14-day osmotic minipumps (OMPs). Results of the first set of studies indicate that subacute and acute deliveries of Phy give essentially comparable protection against 2 or 5 LD50s of soman. The second set of studies show that against soman, the adjuncts scopolamine and trihexyphenidyl when compared, and the carbamates, Phy and Pyr when compared, gave similar protective benefits as indicated by all four monitored measures of toxicity. Phy with either adjunct provided excellent protection against VX induced mortality and convulsions. With both carbamates, trihexyphenidyl gave similar protective benefits against VX. Scopolamine, however, under the conditions used herein, failed to act beneficially with Pyr against VX. PMID- 1889371 TI - The use of uninduced rat liver S-9 to supplement BALB/3T3 cells in the in vitro transformation assay. AB - Because of limited inherent capacity to metabolize chemicals to their reactive form, the BALB/3T3 transformation assay using clone A31-1-1 cells requires metabolic supplementation with rodent liver homogenate preparations (S-9). Activation by S-9 is limited, however, by its cytotoxicity to the cells, thus necessitating a reduction in treatment time from the usual 24-72 to 1-4 hr. With cyclophosphamide (CP) as a test chemical, we were able to increase the treatment time to 24 hr by using lower concentrations of cofactors and S-9 prepared from the livers of untreated rats. Statistically significant increases in transformed foci were induced in cultures treated with 50 or 100 micrograms CP/ml in the presence of 100 or 200 micrograms of uninduced rat liver S-9/ml and 76 or 380 micrograms each of NADH, NADP, NADPH, and glucose-6-phosphate per ml of incubation medium. PMID- 1889372 TI - Assessment of the developmental toxicity of ascorbic acid, sodium selenate, coumarin, serotonin, and 13-cis retinoic acid using FETAX. AB - The developmental toxicity of five compounds was evaluated with the Frog Embryo Teratogenesis Assay: Xenopus (FETAX) and the results were compared to mammalian literature. Small cell Xenopus laevis blastulae were exposed to ascorbic acid, sodium selenate, coumarin, serotonin and 13-cis retinoic acid for 96 hr. Three separate static-renewal assays were conducted for each compound. Teratogenic potential of the test materials was determined based on Teratogenic Index values [TI = LC50/EC50 (malformation)], types and severity of induced malformations and embryo growth. Ascorbic acid had little or no teratogenic potential. Sodium selenate and coumarin tested as having moderately positive teratogenic potential. Serotonin scored as having moderately strong teratogenic potential and 13-cis retinoic acid scored as having strong teratogenic potential. Results were consistent with mammalian data and support the use of FETAX for the screening of developmental toxicants. PMID- 1889373 TI - Assessing the efficacy of an Aroclor 1254-induced exogenous metabolic activation system for FETAX. AB - The developmental toxicity of N-nitrosodimethylamine (NDMA) and trichloroethylene (TCE) was assessed with Frog Embryo Teratogenesis Assay: Xenopus (FETAX). Late Xenopus laevis blastulae were exposed to NDMA and TCE for 96-h in two separate static-renewal tests with and without the presence of three differently induced exogenous metabolic activation systems (MAS). The MAS consisted of Aroclor 1254 induced (Aroclor 1254 MAS), isoniazid-induced (INH MAS), and a post-isolation mixture (mixed MAS) of Aroclor 1254- and isoniazid-induced rat liver microsomes. Addition of the INH MAS and the mixed MAS increased the Teratogenic Index [TI = LC50/EC50 (malformation)] of NDMA and TCE nearly 2.0- and 2.1-fold and 2.1- and 1.7-fold, respectively. Inclusion of the Aroclor 1254 MAS did not alter the developmental toxicity of either compound. Based on TI values, embryo growth, and types and severity of induced malformations, both NDMA and TCE were developmentally toxic. Use of post-microsome isolation mixtures from differentially induced rat livers increased the efficacy of the exogenous MAS routinely used by FETAX. PMID- 1889374 TI - Changes of spontaneous motor activity of rats after acute exposure to tributyltin chloride. AB - The effects of a single acute exposure to tributyltin chloride (TBTCl) on spontaneous motor activity (SMA) in home cage were studied in male Wistar rats. The rats were given TBTCl intraperitoneally at a dosage of 0, 1.6 or 3.3 mg/kg, and the SMA was measured for five days after administration of TBTCl. Body weight gain in the 3.3 mg/kg group was significantly lowered, but that in the 1.6 mg/kg group was comparable to that in the control group. The SMA during light phase was not affected by TBTCl treatment. However, the SMA during dark phase was decreased in both of the TBTCl-treated groups. These decreases in SMA gradually returned to the control levels. The 24-hr total daily and 12-hr nocturnal activity in the TBTCl-treated groups were decreased in a dose-dependent manner. These data indicate that TBTCl possesses behavioral toxicity and suggest that the decreased nocturnal SMA is a sensitive index for detecting toxicity of chemicals in rats. PMID- 1889375 TI - A non-invasive monitoring of exposure to an industrial organic solvent, dimethylformamide. AB - A urinary metabolite, N-hydroxymethyl-N-methyl formamide (DMF-OH) was measured by a colorimetric method in Wistar and Sprague-Dawley rat urine after a single exposure to N,N-dimethyl formamide (DMF). A linear relationship was found between the total excretion of DMF-OH in 2 days versus the exposure ranging from 1 to 20% of the LD50 of DMF i.e. 47.2 to 944 mg DMF per kg b. wt. This is proposed to be a non-invasive biological method for monitoring exposure to DMF. PMID- 1889376 TI - Protection from lethality and behavioral incapacitation resulting from intoxication by soman (pinacolyl methylphosphonofluoridate) and treatment with atropine sulfate and 2-PAM chloride in the guinea pig, cavia porcellus. AB - The lethal and incapacitating effects of the toxic organophosphorus (OP) agent, soman were evaluated in guinea pigs. The protective effects of the standard therapies atropine sulfate (ATR) and pralidoxime chloride (2-PAM) in minimizing or reducing soman-produced lethality and incapacitation (evaluated using a modification of the rat conditioned avoidance procedure) were also studied. At 0.75 and 1.5 LD50 soman was extremely toxic and fast-acting; its effects appeared within five minutes, and its lethal effects occurred within the first three hours. Therapeutic combinations of ATR (64 or 128 mg/kg) and 2-PAM (25 or 100 mg/kg) protected animals from the lethality of soman, but not from its incapacitating effects. However, therapeutic treatment with ATR and 2-PAM also produced a behavioral toxicity in its own right, an effect which lasted for at least three hours in the guinea pig. This behavioral toxicity was lessened by reducing ATR dosage from 128 to 64 mg/kg, but 2-PAM dosage did not influence the behavioral toxicity of the treatment combinations within the range of dosages studied. PMID- 1889377 TI - Differences in the effects of piperine and piperonyl butoxide on hepatic drug metabolizing enzyme system in rats. AB - An i.p. administration of rats with piperine (100 mg/kg) and piperonyl butoxide (400 mg/kg) produced a significant decrease in hepatic cytochrome P-450, and activities of benzphetamine N-demethylase, aminopyrine N-demethylase and aniline hydroxylase 1 hr after the treatment. Twenty-four hr later, these parameters along with cytochrome b5 and NADPH-cytochrome c reductase remained depressed only in piperine-treated rats. In contrast, piperonyl butoxide caused a significant induction of these parameters with the exception of cytochrome b5 and aminopyrine N-demethylase, which were up by 36 and 33% over their respective controls but not significantly. These results point up that effect of piperine on hepatic mixed function oxidases is monophasic while that of piperonyl butoxide is biphasic. PMID- 1889379 TI - Ten- and ninety-day toxicity studies of 1,2-dichlorobenzene administered by oral gavage to Sprague-Dawley rats. AB - Ten- and ninety-day toxicity studies of 1,2-dichlorobenzene (DCB) were conducted in male and female Sprague-Dawley rats to meet the needs of the U.S. Environmental Protection Agency for toxicity data on this chemical for use in their determination of possible health risks related to human exposure. 1,2 Dichlorobenzene was administered at doses of 37.5, 75, 150, and 300 mg/kg/day (10 day), and 25, 100, and 400 mg/kg/day (90-day) in corn oil by oral gavage; control animals received corn oil. At time of sacrifice, gross necropsies were performed and selected tissues were weighed and prepared for histological evaluation. Blood was taken for hematology and clinical chemistries. In the 10-day study, exposure of 300 mg DCB/kg body weight to male rats resulted in a statistically significant decrease in final body weight, organ weights (heart, kidneys, spleen, testes, and thymus), and relative organ weights (spleen and thymus). A significant increase in absolute and relative liver weights was also noted in this dose group. Males also displayed significant increases in water consumption (300 mg/kg group), ALT (300 mg/kg) and leukocyte count (150 and 300 mg/kg). A significant increase in the incidence of hepatocellular necrosis was seen in the 300 mg/kg group of males compared to controls. In the 90-day study, male rats exposed to 400 mg DCB/kg displayed a statistically significant decrease in body weight, organ weight (spleen), and relative organ weight (spleen). The absolute weights of kidney and liver and the relative weights for heart, kidney, liver, lung, brain, and testes were increased significantly for this dose group. The absolute and relative weights of both the kidney and liver were significantly increased in the female 400 mg/kg dose group. The only clinical chemistry parameters statistically different than control were increased ALT (100 and 400 mg/kg groups), BUN and total bilirubin in the male 400 mg/kg group and total bilirubin in the 400 mg/kg female group. Histopathological evaluation showed hepatocellular lesions associated with DCB treatment which included centrolobular degeneration and hypertrophy, and single cell necrosis in male and females receiving 400 mg DCB/kg. The NOAEL observed in this study is 25 mg/kg/day. PMID- 1889378 TI - Toxicity and carcinogenicity studies of nalidixic acid in rodents. AB - Toxicity and carcinogenicity studies of nalidixic acid, an antimicrobial agent used to treat bacterial infections of the urinary tract, were conducted in F344/N rats and B6C3F1 mice of each sex for 13 weeks or 2 years. In the 13-week studies, nalidixic acid was administered at dietary concentrations ranging from 1,000 to 16,000 ppm. Body weights of both rats and mice were reduced in the groups receiving diet containing 8,000 and 16,000 ppm, and feed consumption of rats in the highest treatment groups was approximately two-thirds that of controls. Degeneration of the germinal epithelium in the seminiferous tubules of the testis was observed in male rats that received 16,000 ppm; no other compound-related histopathologic effects were observed in either species. Two-year studies were conducted by feeding diets containing 0, 2,000, or 4,000 ppm nalidixic acid to groups of 50 rats and mice/sex/group. The average daily feed consumption was slightly reduced compared to control groups and resulted in approximate daily doses of 82 or 175 mg nalidixic acid/kg for low dose and high dose rats, and 220 or 475 mg/kg for low dose and high dose mice. Mean body weights of dosed rats and mice were lower than those of controls, except for groups of low dose female rats and male mice. The incidences of preputial gland neoplasms in dosed male rats and of clitoral gland neoplasms in dosed female rats were significantly increased compared to those in controls; responses in low dose groups were similar to those in high dose groups. There were decreased incidences of leukemia and mammary gland neoplasms in dosed female rats and of pituitary gland neoplasms in dosed male rats. Subcutaneous tissue fibrosarcomas were marginally increased in dosed male mice. There were no increased incidences of neoplasms in dosed female mice. Under the conditions of these studies, the dietary administration of nalidixic acid was carcinogenic for rats, causing preputial gland or clitoral gland neoplasms in males and females, respectively. The association of subcutaneous neoplasms with administration of nalidixic acid to male mice was equivocal. PMID- 1889381 TI - Antimicrobials in periodontitis: a clinical approach. PMID- 1889380 TI - Chemotherapeutic mouthrinses. PMID- 1889382 TI - The use of self-instructional materials in dental education as applied to clinical epidemiology and decision making. PMID- 1889383 TI - Job burnout and the dentist. PMID- 1889385 TI - Automated probe: futuristic technology for diagnosis of periodontal disease. PMID- 1889384 TI - Test your diagnostic skills. Central Giant cell granuloma. PMID- 1889386 TI - Localized juvenile periodontitis: a case report. PMID- 1889387 TI - Detection of conformational and net charge differences in DNA-protein complexes by quantitative electrophoresis on polyacrylamide-agarose copolymer gels. AB - The Galactosidase repressor (GalR) of Escherichia coli modulates the expression of the gal operon by binding to two DNA operators, OE and O1. The OE and O1 elements are 16 bp pallindromic DNA sequences, differing in four of the base pairs. OE and O1 DNA fragments, both free and complexed with repressor, were analyzed by "quantitative gel electrophoresis". By the criteria of that method, applied to the linear Ferguson plots of both DNA fragments and the linear ranges of those of the DNA-GalR complexes, it was shown that the apparent size of DNA increases upon repressor binding. Moreover, this size increase is greater for the complex with the O1 operator than for the complex with the OE operator in the case that GalR is located in the center of a 155 bp DNA fragment. This is not the case when GalR is located in a peripheral position. By contrast with their size differences, the centrally located GalR-O1 and GalR-OE complexes appear to possess indistinguishable net surface charge densities as judged from the intercepts with the mobility axis. The larger size of the complex with centrally located O1 fragment, as compared with that bearing the OE fragment, is interpreted as being due to bending of the DNA-protein complex, since an authentically bent fragment of a plasmid with bent upstream activator sequence also exhibits a larger slope of the Ferguson plot, and thus the larger size, than predicted on the basis of its DNA chain length (bp).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1889388 TI - Determining consanguinity by oligonucleotide fingerprinting with (GTG)5/(CAC)5. AB - Simple tandemly organized (GTG)n/(CAC)n sequences are spread throughout the human chromosomes. The most informative DNA fingerprints for the testing of pedigrees and/or paternity were obtained with the simple triplet repeat probe (GTG)5 or its complement (CAC)5. These hypervariable simple-repeat fragments are stably inherited in a Mendelian fashion. Using these highly discriminating probes, all human individuals could, theoretically, be differentiated, except for genetically identical monozygotic twins. Examples from actual case work are reported and pertinent advantages of this methodology are discussed. PMID- 1889389 TI - High-performance capillary electrophoresis of gangliosides. AB - Gangliosides are sialic acid-containing glycosphingolipids. In aqueous media, these glycolipids have been shown to exist as stable micelles. Ganglioside micelles could be analyzed by high-performance zonal capillary electrophoresis in uncoated fused-silica capillaries within 10 min. The mass sensitivity determined by monitoring the absorption of ultraviolet light at 195 nm was in the order of 10(-11) mol. Increasing the pH of the running buffer from 3.0 to 7.4 or the voltage from 10 to 30 kV increased the relative mobilities of gangliosides. By contrast, increasing the ionic strength of the buffer decreased the migration and broadened the elution peak widths of gangliosides. Ganglioside* micelles including GM1, GD1b, and GT1b were resolved into separate peaks by capillary electrophoresis at physiological pH shortly after mixing. Upon prolonged incubation, the ganglioside peaks merged to form a single species. The fusion process was temperature-dependent. At 50 degrees C, formation of mixed micelles between polysialogangliosides GD1b and GT1b was complete within 30 min. In contrast, no fusion of the ganglioside peaks was observed at 0 degrees C even after 75 h. Formation of mixed micelles between GD1b and other polysialogangliosides including GD1a, GT1b, and GQ1b at 37 degrees C required 1.5, 3.0, and 2.0 h, respectively. Formation of mixed micelles between monosialoganglioside GM1 and polysialogangliosides were 6- to 36-fold slower. No fusion was observed between monosialogangliosides GM1 and GM2 after 2 days of incubation. These findings indicate that polysialogangliosides may have higher propensities than monosialoganglioside to form mixed micelles. PMID- 1889390 TI - Analysis of the interaction between human plasma fibronectin and gelatin by affinity electrophoresis. AB - The interaction between human plasma fibronectin and gelatin was analyzed by affinity electrophoresis, in which the fibronectin was subjected to electrophoresis in a 4% polyacrylamide gel in the presence and absence of gelatin, as an affinity ligand, and the fibronectin band was stained by an immunoblotting method. The apparent dissociation constants (Kd) of fibronectin for gelatin were calculated from affinity plots based on the original affinity equation at different pHs, urea concentrations, and temperatures. The fibronectin exhibited much lower affinity in the presence of urea. The Kds at 37 degrees C were 1.49 X 10(-7) M, 2.50 X 10(-6) M, and 3.58 X 10(-6) M with 2 M, 3 M, and 4 M urea, respectively. The van't Hoff plots of Kd values against absolute temperature (T) showed that the value of log Kd decreased in proportion to the increase in the value of 1/T within the range of 15-50 degrees C. The standard enthalpy, the standard free energy change at 37 degrees C, and the entropy change at 37 degrees C for association were calculated to be -124.7 kJ/mol, -33.23 kJ/mol, and -295.1 J/mol/deg, respectively. These results suggest that a hydrophilic interaction, such as hydrogen bond or van der Waals interaction, plays an important role in the binding of plasma fibronectin to gelatin. PMID- 1889391 TI - Quantitative analysis of two-dimensional protein profiles of inbred lines of maize (Zea mays L.). AB - Two-dimensional electrophoresis and fluorography of [35S]methionine labeled maize germinated embryo proteins were performed at Cold Spring Harbor Laboratory. Fluorographs of 63 gels representing 37 inbred lines were subsequently scanned and spot-detected at Protein and DNA Imageware Systems (Huntington Station, NY). The digitized images were then matched with the aid of PDQUEST-II computer software. Over 1500 different protein spots were included in the resulting dataset. The optical density data were normalized to parts per million, then transformed to their natural logarithms. Analyses of variance were performed on each spot in order to select for further study those spots with most of their variation partitioned among inbred lines rather than within inbred lines. Using this method of spot selection, over 100 protein spots were included in the set of spots which display significant differences among inbred lines of maize. PMID- 1889392 TI - Fluctuating bond model of DNA gel electrophoresis. AB - We present a Monte Carlo algorithm that allows a small length scale numerical study of DNA gel electrophoresis in high electric fields, similar to the fluctuating bond model for dynamical properties of polymeric systems. This approach combines advantages of lattice Monte Carlo methods with those from continuous Brownian dynamics algorithms, and also takes into account the persistence length of DNA, as well as the random nature of the gel. The initial orientation and acceleration of a random-walk DNA conformation shows a number of features that can be related to experimental results. The detailed description of DNA motion provided by this approach may lead to a first realistic computer study of the process of DNA sequencing. PMID- 1889393 TI - Application of schlieren optics to real-time monitoring of protein electrophoresis in crosslinker-free linear polyacrylamide solution. AB - Molecular sieving effect of crosslinker-free linear polyacrylamide solutions could be visualized in a real-time mode using schlieren optics for electrophoresis of proteins. Since linear polymer solutions are going to find application in capillary electrophoresis (Zhu, M., et al., J. Chromatogr. 1989, 480, 311-319), the above approach may be useful for obtaining basic data of electrophoresis of proteins and nucleic acids in such media under conditions free from the predominant wall effect pertinent to the use of a capillary. PMID- 1889394 TI - A technique for detecting antifungal activity of proteins separated by polyacrylamide gel electrophoresis. AB - A technique was developed for the detection of antifungal activity of proteins after discontinuous polyacrylamide gel electrophoresis under native conditions. The antifungal activity is detected as growth inhibition zones in a homogeneous fungal lawn, grown in an agar layer spread on top of the polyacrylamide gel. The position of proteins with antifungal activity can be determined on a diffusion blot prepared from the same gel. The technique is illustrated for three antifungal plant proteins, i.e. alpha-purothionin, Urtica dioica agglutinin, and tobacco chitinase. PMID- 1889395 TI - Detection of gelatinolytic enzyme activities after sodium dodecyl sulfate electrophoresis and protein blotting. AB - Visualization of proteases with gelatinolytic activity in sodium dodecyl sulfate gels is described. After conventional sodium dodecyl sulfate-polyacrylamide gel electrophoresis, proteins are transferred onto nitrocellulose membranes preincubated with 0.3% gelatine. During the protein electrotransfer, the proteases are renaturated and their enzymatic activity is restored. After nonspecific protein staining, bands with proteolytic activity appear as white areas on a dark background. PMID- 1889396 TI - Demonstration of murine pancreas elastase and its interstrain variation by isoelectric focusing. AB - Isoelectric focusing between pH 9 and 11 was used for separation of murine pancreas proteases. One of these proteases is characterized by its preference for N-acetyl-L-alanine-alpha-naphthylester as substrate and by its genetic linkage to bt, a coat color marker of chromosome 15. This protease was identified as elastase, and is probably elastase-1 (ELA-1). Because of the simple procedure and the excellent reproducibility of the focusing pattern, ELA-1 is recommended as a useful marker for mouse chromosome 15. PMID- 1889397 TI - Effect of hair dyes and bleach on the hair protein patterns as revealed by isoelectric focusing. AB - The effect of hair dyes, i.e., temporary, semi-permanent, or permanent hair dyes, or hair bleach on the isoelectric focusing (IEF) hair protein patterns was studied. A permanent hair dye (metallic, alkaline oxidative, or acidic oxidative) and hair bleach induced changes in the IEF hair protein patterns and in the intensity of hair protein bands. The changes in the IEF patterns, caused by the alkaline oxidative dye or the bleach, are considered to result from the combined effect of an alkaline agent and an oxidative agent in the alkaline oxidative dye and in the hair bleach. PMID- 1889398 TI - The ATP requirement for initiation of eukaryotic translation varies according to the mRNA species. AB - The requirement for ATP for initiation of eukaryotic mRNA translation was tested using gel-filtered rabbit reticulocyte lysates incubated with labelled Met tRNAfMet and exogenous RNA templates, and assaying the formation of labelled 80S initiation complexes in the presence of GTP, or labelled 40S initiation complexes in the presence of a non-hydrolysable analogue of GTP. Initiation complex formation on globin mRNA, or on capped viral RNAs such as papaya mosaic virus RNA and tobacco mosaic virus RNA, was strongly stimulated by ATP. In contrast, initiation complex formation on (uncapped) encephalomyocarditis virus RNA was uninfluenced by the presence or absence of ATP, which may be correlated with the recent evidence for scanning-independent internal initiation on this viral RNA. In addition, initiation complex formation on uncapped cowpea mosaic virus RNA and on poly(A,U,G) was only slightly stimulated by ATP, much less than in the case of the capped RNAs. These results suggest that most of the ATP hydrolysed during translation initiation is consumed in cap-dependent processes, probably in unwinding the mRNA, and relatively little in the actual migration or scanning of 40S subunits along the mRNA. PMID- 1889399 TI - Effect of Thermus thermophilus elongation factor Ts on the conformation of elongation factor Tu. AB - Affinity labeling in situ of the Thermus thermophilus elongation factor Tu (EF Tu) nucleotide binding site was achieved with periodate-oxidized GDP (GDPoxi) or GTP (GTPoxi) in the absence and presence of elongation factor Ts (EF-Ts). Lys52 and Lys137, both reacting with GDPoxi and GTPoxi, are located in the nucleotide binding region. In the absence of EF-Ts Lys137 and to a lesser extent Lys52 were accessible to the reaction with GTPoxi. GDPoxi reacted much more efficiently with Lys52 than with Lys137 under these conditions [Peter, M. E., Wittman-Liebold, B. & Sprinzl, M. (1988) Biochemistry 27, 9132-9138]. In the presence of EF-Ts, GDPoxi reacted more efficiently with Lys137 than with Lys52, indicating that the interaction of EF-Ts with EF-Tu.GDPoxi induces a conformation resembling that of the EF-Tu.GDPoxi complex in the absence of EF-Ts. Binding of EF-Ts to EF-Tu.GDP enhances the accessibility of the Arg59-Gly60 peptide bond of EF-Tu to trypsin cleavage. Hydrolysis of this peptide bond does not interfere with the ability of EF-Ts to bind to EF-Tu. EF-Ts is protected against trypsin cleavage by interaction with EF-Tu.GDP. High concentrations of EF-Ts did not interfere significantly with aminoacyl-tRNA.EF-Tu.GTP complex formation. PMID- 1889400 TI - Characterization of Hex2 protein, a negative regulatory element necessary for glucose repression in yeast. AB - The regulatory HEX2 gene plays an important role in glucose repression in the yeast Saccharomyces cerevisiae. The hex2 mutants have pleiotropic defects in the regulation of glucose-repressible enzymes, hexokinase PII synthesis and maltose uptake [Entian, K.-D. & Zimmermann, F.K. (1980) Mol. Gen. Genet. 177, 345-350]. The HEX2 gene encodes a protein of 114137 Da, deduced from its DNA sequence. There were no strong similarities to previously known genes. HEX2-lacZ fusions revealed a largely constitutive expression when repressing and non-repressing growth conditions were compared. Cellular fractionation studies indicated a nuclear localization of the Hex2 protein. The hex2 mutation was shown to be allelic to reg1, which releases galactose pathway enzymes from glucose repression [Matsumoto, K., Yoshimatsu, T. & Oshima, Y. (1983) J. Bacteriol. 153, 1405-1414]. Overexpression of HEX2 resulted in a 70% reduction of GAL1 expression under induced growth conditions. Our studies support the view that protein Hex2 is a negative regulatory element in glucose repression which may directly influence transcription, possibly by interaction with transcriptional factors. Deletion experiments identified a central core of Hex2, spanning only 492 out of 1026 amino acid residues, as mainly important for glucose repression. There are two strongly acidic regions within this part of the protein, their possible importance is discussed. PMID- 1889401 TI - Association of ribosomal subunits. A new functional role for yeast EF-1 alpha in protein biosynthesis. AB - A yeast ribosomal subunit association factor (AF) has been purified from a high salt ribosomal wash. The purified enzyme is a thermostable protein that associates ribosomal subunits at low Mg2+ concentration without requiring energy. It appears to be an aggregate of trimers or dimers (molecular mass 125 or 79 kDa) which on sodium dodecyl sulfate gels shows the presence of a major protein band whose estimated molecular mass is 43 kDa. Evidence also indicates the existence of a 50-kDa polypeptide which seems to be unstable since with freezing and thawing it gives rise to the 43-kDa polypeptide. It was shown that the labelled factor interacts with 80S ribosomes and with 40S ribosomal subunits. The purified polypeptide reacts with antibodies directed against EF-1 alpha, this last protein recognizing the antibodies raised against AF. Likewise, both EF-1 alpha and AF associate ribosomal subunits in the same way. When EF-1 is heated, it not only maintains its association activity, but also behaves like a 43-kDa polypeptide in an SDS electrophoresis run. These observations strongly suggest that AF originates from EF-1 alpha, which implies that the well-known elongation factor may also play a role in the initiation step of protein synthesis. PMID- 1889402 TI - Cytoplasmic aspartyl-tRNA synthetase from Saccharomyces cerevisiae. Study of its functional organisation by deletion analysis. AB - Aspartyl-tRNA synthetase (AspRS) from yeast, a homodimer of 125 kDa, was shortened by several residues from the C- and N-termini, via site-directed mutagenesis, to examine the contribution of the removed peptides to the enzyme properties. This study showed that the N-terminal sequence up to amino acid 70 (which confers peculiar ionic properties to the protein) is dispensable for activity. Domains located beyond amino acid 70 appeared to have increasing catalytic importance; the removal of 80 or 90 residues affected the Km values for ATP and deletions of 101 or 140 amino acids profoundly modified the physiochemical properties of AspRS, and by consequence, its structural organisation (extraction of the mutated proteins out of the cells required the presence of SDS). On the C-terminal side, very limited modifications readily affected the enzyme properties. Deletion of as few as three residues increased the Km for ATP and reduced the aminoacylation kcat as well as the thermostability of the adenylate synthesis activity; the kcat of this step was impaired after deletion of two further residues. Finally, shortening the C-terminal decapeptide completely inactivated AspRS, whilst affecting neither its affinity for tRNAAsp nor its dimerisation capacity. These data reveal the role of the C-terminal decapeptide as a determinant in both reactions catalysed by AspRS. This peptide is involved in ATP binding, stabilising the functional conformation of the amino acid-activating domain and probably maintaining the tRNA-acceptor end in a reactive position with regard to the activated amino acid. PMID- 1889403 TI - Tendamistat (12-26) fragment. NMR characterization of isolated beta-turn folding intermediates. AB - In order to determine whether regions of a protein that are turns in the native structure are able to maintain such a structure when isolated, we have studied the conformational properties of various peptide fragments corresponding to the 12-26-peptide region of the alpha-amylase inhibitor tendamistat, by NMR. Amide solvent accessibility, NOE spectroscopy (NOESY) and rotating-frame NOE spectroscopy (ROESY) data strongly support the conclusion that the 12-26 and 15 23 peptides adopt in aqueous solution, a set of turn-like structures located around the central region of their corresponding polypeptidic chains, the same region where a beta turn exists in the native protein. Such a set of structures are destabilized when one residue located within the native beta turn of the 15 23 peptide is modified Trp18----Ser. Our results indicate that the tendency to bend in a predetermined region of a protein chain seems to exist from the very beginning of the folding process and therefore it could drive the folding instead of being a consequence of the tertiary assembly of the protein. PMID- 1889404 TI - An intra-dimeric crosslink of large subunits of spinach ribulose-1,5-bisphosphate carboxylase/oxygenase is formed by oxidation of cysteine 247. AB - Crystals of the hexadecameric form of ribulose-bisphosphate carboxylase used to solve the structure of the enzyme are composed of protein substantially crosslinked by a disulfide bond between pairs of large subunits. Conditions leading to the selective formation of dimers of the large subunits are described. The stability and specificity of the intra-dimeric crosslink was used to confirm that only one cysteine residue, Cys247 of neighboring large subunits, is involved in the bridge. The ability to generate this disulfide selectively, or alternatively replace the cysteine by site-directed mutagenesis, has led us to conclude that there is no effect of these changes on any of the critical kinetic parameters of the enzyme. The benign effect of the oxidation indicates that the crystal structures of the ribulose-bisphosphate carboxylase, particularly of the active site, are a true representation of the native enzyme. PMID- 1889405 TI - Nuclear magnetic resonance studies of recombinant Escherichia coli glutaredoxin. Sequence-specific assignments and secondary structure determination of the oxidized form. AB - Escherichia coli glutaredoxin (85 amino acid residues, Mr = 9100), the glutathione-dependent hydrogen donor for ribonucleotide reductase, was purified from an inducible lambda PL, expression system both with a natural isotope content and with uniform 15N labelling. This material was used for obtaining sequence-specific 1H magnetic resonance assignments and the identification of regular secondary structures in the oxidized form of the protein, which contains the redox-active disulfide Cys11-Pro-Tyr-Cys14. Oxidized glutaredoxin contains a four-stranded beta-sheet, with the peripheral strand 32-37 arranged parallel to the strand 2-7, which further combines with the two additional strands 61-64 and 67-69 in an antiparallel fashion. The protein further contains three helices extending approximately from residues 13-28, 45-54 and 72-84. PMID- 1889406 TI - Molecular structure of human protamine P4 (HP4), a minor basic protein of human sperm nuclei. AB - Protamine HP4 is a minor protein which was purified from human sperm nuclei. It was characterized by its amino acid composition, peptide mapping after digestion with highly specific endoproteinases and finally by its amino acid sequence. Protamine HP4 contains high amounts of arginine, cysteine and histidine. The primary structure of the protein was established by sequence analysis of intact protamine and of its fragments. HP4 is a P2-type protamine of 58 residues (Mr 7783) structurally related to human protamines HP2 and HP3 from which it only differs by an amino-terminal extension of one and four residues, respectively. These three protamines exhibit a close structural relationship with mouse protamine mP2. The heterogeneity of protamines in human sperm nuclei is discussed. PMID- 1889407 TI - Glycosphingolipids in insects. The amphoteric moiety, N-acetylglucosamine-linked phosphoethanolamine, distinguishes a group of ceramide oligosaccharides from the pupae of Calliphora vicina (Insecta: Diptera). AB - A group of Calliphora vicina pupal glycolipids could be segregated from the neutral glycosphingolipids, according to their two-dimensional TLC migration properties and positive reactions toward ninhydrin and fluorescamine spray reagents. These classified zwitterionic glycolipids were isolated by silica-gel column chromatography and characterized by the presence of a N-acetyl-glucosamine bound phosphoethanolamine residue. The structural elucidation of the oligosaccharide moieties was performed by the determination of constituent carbohydrates as alditol acetates, linkage analysis by permethylation, exoglycosidase cleavage, fast-atom-bombardment mass spectrometry and NMR spectroscopy. The dominant fatty acid and sphingoid base species of the ceramide moieties were C20:0 (arachidic acid) and C14:1 (tetradecasphing-4-enine), respectively. The chemical structures of the zwitterionic, biogenetic glycosphingolipid series were determined as: (PEtn-6')GlcNAc(beta 1-3)Man(beta 1 4)Glc beta Cer; GalNAc(beta 1-4)(PEtn-6')GlcNAc(beta 1-3)Man(beta 1-4)Glc beta Cer; GalNAc(alpha 1-4)GalNAc(beta 1-4)(PEtn-6')GlcNAc(beta 1-3)Man(beta 1- 4)Glc beta Cer; Gal(beta 1-3)GalNAc(beta 1-4)(PEtn-6')GlcNAc(beta 1-3)Man(beta 1-4)Glc beta Cer; Gal(beta 1-3)GalNAc(alpha 1-4)GalNAc(beta 1-4)(PEtn-6')GlcNAc(beta 1- 3)Man(beta 1-4)Glc beta Cer; GlcNAc(beta 1-3)Gal(beta 1-3)GalNAc(alpha 1 4)GalNAc(beta 1-4)(PEtn- 6')GlcNAc(beta 1-3)Man(beta 1-4)Glc beta Cer. PMID- 1889409 TI - Kappa-casein micelles: structure, interaction and gelling studied by small-angle neutron scattering. AB - Small-angle neutron scattering (SANS) measurements on dilute and concentrated dispersions of kappa-casein micelles in a buffer at pH = 6.7 were made using the D11 diffractometer in Grenoble. Results indicate that the micelles have a dense core with a fluffy outer layer. This outer layer appears to give rise to a steeply repulsive interaction on contact. In fact, the hard-sphere model best fits the measured scattering intensities. Adding chymosin to the dispersion initiated a fractal flocculation of the micelles and consecutively a coalescence of the micelles. This unexpected second process resembled that of spinodal demixing. The dispersion phase thus separates into a water and a protein phase on a time scale of hours. The observed phenomona contribute to the understanding of the cheese-making process. PMID- 1889408 TI - Conformational dynamics and solvent viscosity effects in carboxypeptidase-A catalyzed benzoylglycylphenyllactate hydrolysis. AB - We have used a new approach to the dynamics of hydrolytic metalloenzyme catalysis based on investigations of both external solvent viscosity effects and kinetic 2H isotope effects. The former reflects solvent and protein dynamics, and the nuclear reorganization distribution among damped protein motion and intramolecular friction-free nuclear motion. The isotope effect represents proton tunnelling and reorganization in the hydrogen bond network around the active site. We illustrate the approach by new spectrophotometric and pH-titration data for carboxypeptidase-A-catalyzed benzoylglycyl-L-phenyllactate hydrolysis. This substrate exhibits both a significant inverse fractional power law viscosity dependence over wide ranges controlled by glycerol and sucrose, and a kinetic 2H isotope effect of 1.65. The analogous benzoylglycylphenylalanine hydrolysis has a smaller isotope effect (1.3) and no viscosity dependence. Viscosity variation has no effect on the CD spectra in the 180-240-nm range. In terms of stochastic chemical rate theory, the data correspond to an enzyme-peptide substrate complex with a 'tight' structure protected from the solvent. In comparison, the enzyme ester substrate complex is 'softer', strongly coupled to the solvent, and the rate-determining step is accompanied by proton transfer or by substantial reorganization in the hydrogen bonds near the active site. PMID- 1889410 TI - Activation of the fibrinogen receptor on human platelets exposed to alpha chymotrypsin. Relationship with a major proteolytic cleavage at the carboxyterminus of the membrane glycoprotein IIb heavy chain. AB - The serine proteinase alpha chymotrypsin from bovine pancreas (CT) is known to expose fibrinogen binding sites on the surface of human platelets in the absence of cell activation and granular secretion. This is accompanied by the appearance of membrane-bound chymotryptic fragments of both glycoprotein (GP) IIb and GPIIIa, the two subunits of the platelet fibrinogen receptor, the GPIIb-IIIa complex. However, no clear relationship between discrete proteolytic event(s) within GPIIb-IIIa and fibrinogen-binding-site expression has yet been established. We have now evaluated the proteolysis of GPIIb-IIIa by CT by Western blot analyses using a panel of polyclonal and monoclonal antibodies against GPIIb or GPIIIa. The different proteolytic events were then correlated with the kinetics of the expression of active fibrinogen binding sites on platelets, as measured through the binding of 125I-labelled purified fibrinogen and to the capacity of CT-treated platelets to aggregate. Treatment of platelets with CT at 22 degrees C resulted in the expression of fibrinogen binding sites prior to cleavage of GPIIIa (Mr approximately 90,000) into a previously described, major membrane-bound fragment with Mr 60,000. In contrast, fibrinogen receptor expression closely paralleled a proteolytic cleavage at the carboxy terminus of the GPIIb heavy chain (Mr approximately 120,000), which was converted into a faster migrating species with Mr approximately 115,000). This proteolysis resulted in the release of a soluble peptide with an expected molecular mass of less than 3.7 kDa. Quantitation of this peptide using a competitive immunoenzymatic assay, confirmed that its release from the platelet surface correlated with the expression of fibrinogen binding sites and aggregability. When platelets were exposed to CT at 37 degrees C, a prompt increase in fibrinogen binding sites and platelet aggregability was observed, whereas the GPIIb heavy chain was rapidly converted into the carboxy-terminal-cleaved form. However, incubation at 37 degrees C for longer than 10 min resulted in extensive and simultaneous degradation of both the GPIIb heavy and light chains and of GPIIIa, with the latter being converted into the 60-kDa fragment. These later events were associated with a sharp decline of platelet aggregability and a reduction in the number of fibrinogen binding sites. These data allow us to propose that an early and limited proteolytic processing of the GPIIb component of the platelet fibrinogen receptor is associated with a shift of this receptor complex into a state which expresses specific binding sites for fibrinogen. Further cleavage of GPIIIa to generate the 60-kDa fragment results in loss of receptor activity. PMID- 1889411 TI - Evidence for the existence of distinct transporters for the polyamines putrescine and spermidine in B16 melanoma cells. AB - The uptake of intracellular putrescine and spermidine was examined in B16 melanoma cells. It was found that difluoromethylornithine preferentially induced putrescine transport (28-fold) compared to that for spermidine (3.5-fold). Putrescine uptake was partially Na+ dependent, whereas spermidine uptake was not. Inhibition studies with the two polyamines showed that putrescine was a poor competitive inhibitor of spermidine uptake, exhibiting a Ki of 69-75 microM, whereas the estimated Km for putrescine uptake was only 5.36 microM. By contrast, spermidine inhibition of putrescine transport produced a non-linear Eadie Scatchard plot suggesting that putrescine was taken up by a spermidine-sensitive and a spermidine-insensitive process. The estimated spermidine Ki for inhibition of the spermidine-sensitive process was 0.125 microM. Using a series of polypyridinium quaternary salts to inhibit transport, no correlation between inhibition of putrescine uptake and inhibition of spermidine uptake was seen. Finally, the photoaffinity label, 1,12-di(N5-azido-2-nitrobenzoyl)spermine selectively inactivated the putrescine transporter(s) without affecting spermidine uptake. From these observations, it was concluded that multiple polyamine transporters are present on B16 melanoma cells and that separate, distinct transporter(s) account for the uptake of putrescine and spermidine in this cell-line following induction with difluoromethylornithine. The present of different transporters for the two polyamines indicates that expression of uptake activity for putrescine and spermidine may be under separate cellular control. PMID- 1889412 TI - Kinetic studies of the variations of cytoplasmic pH, nucleotide triphosphates (31P-NMR) and lactate during normoxic and anoxic transitions in maize root tips. AB - We have followed the dynamic evolution of intracellular pH and of the intracellular concentration of nucleotides (NDP, NTP), Pi and lactate in maize root tips during the course of normoxia and anoxia transition. The intracellular pH, determined from the 31P-NMR chemical shift of the cytoplasmic P1 peak, dropped from 7.5 to 6.9 during the first few minutes after anaerobiosis. It increased again, then settled to a steady-state value of 7.1-7.2, 25 min after the beginning of the anoxic treatment. Following oxygenation, the chemical shift of the cytoplasmic Pi peak drifted gradually to its initial value. The cytoplasmic pH followed an oscillatory time course which was almost identical to the time course of NTP. Intracellular lactate accumulated steadily during the first 30 min after anaerobiosis, then its intracellular concentration remained almost constant. Following oxygenation, the intracellular concentration of lactate decreased slowly. The cytoplasmic pH followed a time course which was not identical to the time course of lactate. Following hypoxia, the pH dropped to low values long before the intracellular lactate concentration reached a steady-state equilibrium. Conversely, subsequent to oxygenation, the pH returned to normal values long before lactate. These results do not agree with the statement that cytoplasmic acidification in hypoxic maize root tips is necessarily associated with lactic acid synthesis. PMID- 1889413 TI - Identification and characterization of a Saccharomyces cerevisiae gene (PAR1) conferring resistance to iron chelators. AB - o-Phenanthroline (1,10-phenanthroline) is a chemical known to chelate iron and other transition metal ions. This compound was added to solid yeast media to reduce the concentration of biologically available iron. Other essential divalent cations, like Zn2+ or Cu2+, which could also be bound, were supplemented. Growth of wild-type yeast strains was totally inhibited at specific concentrations of the chelator. However, several cells containing plasmids of a multicopy vector genomic library of S. cerevisiae could be selected by growth on these media. All of the resistant clones carried a single additional gene, PAR1 on their multicopy plasmids. Plasmid-directed overexpression of PAR1 increased the resistance of transformants to o-phenanthroline and additionally conferred resistance to 1 nitroso-2-naphthol, an iron(III)-binding molecule with different coordinating ligands. By supplementing the o-phenanthroline-containing media with several different metal ions, it could be proved that the selection plates really caused a specific iron limitation. These observations clearly demonstrated that the overexpressed PAR1 gene enables the cell to compete with iron-chelating organic molecules. PAR1 null mutants, constructed by insertion of the LEU2 gene into the open reading frame, showed a remarkable phenotype: they did not grow on slightly alkaline buffered media (pH greater than 7) and became hypersensitive to oxidative stress by hydrogen peroxide. Of several heavy metal ions, such as Fe3+, Fe2+, Co2+, Ni2+, Cu2+ and Zn2+, tested for supplementation of the alkaline growth deficiency, only iron, either added in the ferrous or ferric form, was able to restore cellular growth. It can be concluded from the DNA sequence that PAR1 encodes a highly acidic protein of 650 residues with mostly hydrophilic character. Some interesting repetitive amino acid motifs, such as (Asp-Asn)4 or Cys-Ser-Glu, may act as metal-binding sites. The possible role of PAR1 is discussed. PMID- 1889414 TI - Induction, regulation and messenger half-life of cytochromes P450 IA1, IA2 and IIIA6 in primary cultures of rabbit hepatocytes. CYP 1A1, 1A2 and 3A6 chromosome location in the rabbit and evidence that post-transcriptional control of gene IA2 does not involve mRNA stabilization. AB - A study on the regulation and induction of expression of cytochromes P450-IA1, IA2 and IIIA6 genes has been undertaken using primary cultures of adult rabbit hepatocytes grown in a serum-free chemically and hormonally defined medium. In 72 h-old cultures, 50 microM beta-naphthoflavone induced both IA1 and IA2 mRNA, the maximal level being reached after 4 h and 12 h, respectively. This was shown to result from an increase in the rate of transcription of gene IA1. In contrast, gene IA2 was constitutively transcribed in untreated cells, but mRNA only accumulated in the presence of beta-naphthoflavone which, however, did not affect the rate of transcription. Actinomycin D fully blocked induction of both IA1 and IA2 mRNA in response to their inducer. In untreated cells the presence of cycloheximide allowed a 'constitutive' expression of gene IA1, while in beta naphthoflavone-treated cells, it produced a super-induction of IA1 but no modification of IA2 gene expression. Rifampicin (50 microM) strongly increased the IA1 mRNA level and rate of transcription only in cycloheximide-treated cells. Rifampicin and dexamethasone, two prototypical inducers of P450-IIIAs, induced both large and small IIIA6 mRNAs in a time-dependent fashion, the maximum level being reached after 24 h. This was related to a large increase in the rate of transcription of the gene. Cycloheximide significantly decreased the accumulation of both IIIA6 mRNAs in response to rifampicin, while actinomycin D fully blocked induction. The half-lives of IA1, IA2 and IIIA6 mRNAs were determined by two different methods, namely actinomycin D and [3H]uridine-chase experiments. In untreated cells, the half-lives for IA1, IA2 and IIIA6 mRNAs were 14 h, 16 h and 19 h, respectively when determined by the uridine chase and 18 h, 25 h and 22 h when determined by the actinomycin-D chase. These values were not modified significantly in cells treated with beta-naphthoflavone or rifampicin, indicating that neither of these inducers affected the stability of IA1 and IA2 or IIIA6 messages, respectively.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1889415 TI - Isolation and characterization of a cytochrome P450 of the IIA subfamily from human liver microsomes. AB - Antibodies raised against cytochrome P450, which is overexpressed in mouse hepatic tumors, (P450tu) crossreact with two human liver microsomal proteins (49 kDa and 52 kDa). We have quantified these proteins in 60 human liver samples and found great interindividual variability in both of them. The concentration of the 49-kDa protein varies up to 144 fold in the various samples and represents typically 10% of the total mincrosomal P450 content. Its immunologically determined concentration correlates well (R = 0.78) with the microsomal coumarin 7-hydroylase (COH) activity. This activity is strongly and completely inhibited by anti-P450tu antibody (IC50 = 0.13 mg IgG/mg microsomal protein). The crossreacting 49-kDa protein shows an unusually high substrate specificity towards coumarin; it presents all human COH and part of 7-ethoxycoumarin O deethylase (ECOD). Besides these two activities, we did not find any activity with other typical P450 substrates. In primary cultures of human hepatocytes, it is inducible by phenobarbital and dexamethasone, but not by pyrazole and beta naphthoflavone. We isolated this protein from human liver microsomes and purified it to homogeneity by a combination of aminooctyl-amino-Sepharose chromatography and immunoaffinity chromatography. The protein was identified as a cytochrome P450 of the IIA subfamily. Its N-terminal amino-acid sequence was identical with the first 20 residues deduced from the nucleotide sequence of P450IIA6. PMID- 1889416 TI - Characteristics of short-chain alcohol dehydrogenases and related enzymes. AB - Different short-chain dehydrogenases are distantly related, constituting a protein family now known from at least 20 separate enzymes characterized, but with extensive differences, especially in the C-terminal third of their sequences. Many of the first known members were prokaryotic, but recent additions include mammalian enzymes from placenta, liver and other tissues, including 15 hydroxyprostaglandin, 17 beta-hydroxysteroid and 11 beta-hydroxysteroid dehydrogenases. In addition, species variants, isozyme-like multiplicities and mutants have been reported for several of the structures. Alignments of the different enzymes reveal large homologous parts, with clustered similarities indicating regions of special functional/structural importance. Several of these derive from relationships within a common type of coenzyme-binding domain, but central-chain patterns of similarity go beyond this domain. Total residue identities between enzyme pairs are typically around 25%, but single forms deviate more or less (14-58%). Only six of the 250-odd residues are strictly conserved and seven more are conserved in all but single cases. Over one third of the conserved residues are glycine, showing the importance of conformational and spatial restrictions. Secondary structure predictions, residue distributions and hydrophilicity profiles outline a common, N-terminal coenzyme-binding domain similar to that of other dehydrogenases, and a C-terminal domain with unique segments and presumably individual functions in each case. Strictly conserved residues of possible functional interest are limited, essentially only three polar residues. Asp64, Tyr152 and Lys156 (in the numbering of Drosophila alcohol dehydrogenase), but no histidine or cysteine residue like in the completely different, classical medium-chain alcohol dehydrogenase family. Asp64 is in the suggested coenzyme-binding domain, whereas Tyr152 and Lys156 are close to the center of the protein chain, at a putative inter-domain, active-site segment. Consequently, the overall comparisons suggest the possibility of related mechanisms and domain properties for different members of the short-chain family. PMID- 1889417 TI - Competitive inhibition of liver glucokinase by its regulatory protein. AB - The regulatory protein of rat liver glucokinase (hexokinase IV or D) behaved as a fully competitive inhibitor of this enzyme when glucose was the variable substrate, i.e. it increased the half-saturating concentration of glucose as a linear function of its concentration without affecting V (velocity at infinite concentration of substrate). The inhibition by the regulatory protein and that by palmitoyl-CoA were synergistic with that by N-acetyl-glucosamine, indicating that the two former inhibitors bind to a site distinct from the catalytic site. In contrast, the effects of the regulatory protein and palmitoyl-CoA were competitive with each other, indicating that these two inhibitors bind to the same site. The regulatory protein exerted a non-competitive inhibition with respect to Mg-ATP at concentrations of this nucleotide less than 0.5 mM. At higher concentrations, the latter antagonized the inhibition by the regulatory protein partly by decreasing the apparent affinity for fructose 6-phosphate. The following anions inhibited glucokinase non-competitively with respect to glucose: Pi, sulfate, I-, Br-, No3-, Cl-, F- and acetate. Pi and sulfate, at concentrations in the millimolar range, decreased the inhibition by the regulatory protein by competing with fructose 6-phosphate. Monovalent anions also antagonized the inhibition by the regulatory protein with the following order of potency: I- greater than Br- greater than NO3- greater than Cl- greater than F- greater than acetate and their effect was non-competitive with respect to fructose 6-phosphate. Glucokinase from Buffo marinus and pig liver were, like the rat liver enzyme, inhibited by the regulatory protein, as well as by palmitoyl CoA at micromolar concentrations. In contrast, neither compound inhibited hexokinases from rat brain, beef heart or yeast, or the low-Km specific glucokinase from Bacillus stearothermophilus. PMID- 1889418 TI - Effectors of the regulatory protein acting on liver glucokinase: a kinetic investigation. AB - In the absence of fructose 6-phosphate, the regulatory protein of rat liver glucokinase (hexokinase IV or D) inhibited this enzyme, though with a much (15 fold) lower potency than in the presence of a saturating concentration of fructose 6-phosphate. Evidence is provided that this inhibition is not due to contaminating fructose 6-phosphate. In the presence of regulatory protein, sorbitol 6-phosphate, a potent analog of fructose 6-phosphate, exerted a hyperbolic, partial inhibition on glucokinase, the degree of which increased with the concentration of regulatory protein. Plots of the reciprocal of the difference between the rates in the absence and in the presence of sorbitol 6 phosphate versus 1/[sorbitol 6-phosphate] at various concentrations of regulatory protein were linear, and demonstrated that the apparent affinity for sorbitol 6 phosphate increased with the concentration of regulatory protein. Plots of the reciprocal of the difference between 1/v in the presence and in the absence of sorbitol 6-phosphate versus 1/[sorbitol 6-phosphate] were also linear and crossed the axis at a value independent of the concentration of regulatory protein. Fructose 1-phosphate released the inhibition exerted by the regulatory protein in a hyperbolic fashion. The concentration of this effector required for a half maximal effect increased linearly with the concentrations of sorbitol 6-phosphate and of regulatory protein. These results are consistent with a model in which the regulatory protein exists under two conformations, one form which binds inhibitors and glucokinase, and the other which binds activators, although not glucokinase. Sorbitol 6-phosphate, 2-deoxysorbitol 6-phosphate and mannitol 1 phosphate, all analogs of the open-chain configuration of fructose 6-phosphate, inhibited glucokinase in the presence of regulatory protein at lower concentrations than fructose 6-phosphate, whereas fixed analogs of the furanose form of fructose 6-phosphate were inactive or behaved as activators. This indicated that fructose 6-phosphate in its open-chain configuration is recognized by the regulatory protein. A series of compounds exerted an activating effect. These included, in order of decreasing potency: fructose 1-phosphate, psicose 1 phosphate, ribitol 5-phosphate, analogs of fructose 1-phosphate and of ribitol 5 phosphate and, at much higher concentrations, inorganic phosphate. PMID- 1889419 TI - A membrane-bound metallo-endopeptidase from rat kidney hydrolyzing parathyroid hormone. Purification and characterization. AB - A metallo-endopeptidase, which appears to be an integral membrane protein of rat kidney, was purified to homogeneity by a series of standard chromatographic procedures. This enzyme significantly hydrolyzed human parathyroid hormone [hPTH(1-84)] and a synthetic substrate Suc-Leu-Leu-Val-Tyr-Mec (Suc = succinyl, Mec = 4-methyl-coumarinyl-7-amide). The purified enzyme had apparent molecular masses of 250 kDa on gel filtration, and 88 kDa and 245 kDa on sodium dodecyl sulfate/polyacrylamide gel electrophoresis under reducing and non-reducing conditions, respectively. Its pH optimum for activity was 8.0-8.5 and its isoelectric point was pH 4.9. Its activity was inhibited by EDTA, EGTA and o phenanthroline, but not by phosphoramidon. The metal-depleted enzyme was reactivated by the addition of metal ions. The enzyme was also inhibited by chymostatin and eglin C, and by thiol compounds. Of the synthetic substrates examined, the enzyme hydrolyzed only Suc-Leu-Leu-Val-Tyr-Mec, one of the synthetic substrates for alpha-chymotrypsin. It did not hydrolyze synthetic substrates with less than four amino acid residues with tyrosine in the P1 position. The enzyme hydrolyzed hPTH and reduced hen egg lysozyme but did not hydrolyze azocasein or [3H]methyl-casein. NH2-terminal amino acid sequence analyses of the degradation products of hPTH(1-84) and reduced hen egg lysozyme by the purified enzyme revealed that the enzyme preferentially cleaved these peptides at peptide bonds flanked by hydrophilic amino acid residues. Amino acid analyses showed that the main degradation products of PTH were hPTH(17-29), hPTH(30-38) and hPTH(74-84). The ability of the enzyme to hydrolyze peptide bonds flanked by hydrophilic amino acid residues and its inability to degrade azocasein distinguish it from several other kidney endopeptidases reported, such as endopeptidase 24.11 and meprin. PMID- 1889420 TI - Cell-cycle-dependent, differential prenylation of proteins. AB - Isoprenylated proteins related to cell growth have been detected during proliferation. Since cholesterogenesis (isoprenoid synthesis) is mandatory for cell proliferation, the observation of a temporally coordinated protein prenylation during the cell division cycle might constitute obligatory processes in the signalling pathway for initiating DNA replication and/or in maintaining the growing state. We have found such a definitive cell-cycle-phase-dependent pattern of prenylation for various classes of cytosolic and nuclear matrix proteins in synchronized HepG2 cells. Characteristic [3H]mevalonate incorporation began to increase during mid-to-late G1, just after cholesterol synthesis reached its apex, and peaked just prior to or coincident with mid S. Incorporation then declined subsequent to S (during G2) as cells approached mitosis. Prior to the rise in mevalonate incorporation into proteins, during early-to-mid G1, steady state [14C]acetate incorporation into chromatographically resolved cholesterogenic lipid intermediates displayed a maximum only into cholesterol. However, during the late-G1/S interval, a singular peak of 14C incorporation was found for the farnesyl moiety (farnesol/nerolidol plus farnesyl diphosphate). Except for the farnesyl moiety, none of the other polyisoprenoids detected by our procedures showed any fluctuation in 14C incorporation subsequent to mid G1. These results support the proposal that subsequent to peak cholesterol synthesis in early-to-mid G1, the generation of a cholesterol-pathway-dependent set of post translationally modified, polyisoprenylated proteins could constitute an obligatory step leading to the duplication of the cellular genome, thereby impelling transit through the cell cycle. The well known high flux through cholesterogenesis in tumors, which manifests an intrinsic lack of sensitivity to feedback inhibition and operates continuously, is consonant with this proposal. PMID- 1889421 TI - Glycosphingolipid specificity of the human sulfatide activator protein. AB - The interaction of the sulfatide activator protein with different glycosphingolipids have been studied in detail. The following findings were made. 1. The sulfatide activator protein forms water-soluble complexes with sulfatides [Fischer, G. and Jatzkewitz, H. (1977) Hoppe-Seyler's Z. Physiol. Chem. 356, 6588 6591] and various other glycospingolipids. 2. In the absence of degrading enzymes the activator protein acts in vitro as a glycosphingolipid transfer protein, transporting glycosphingolipids from donor to acceptor liposomes. Lipids having less than three hexoses, e.g. galactosylceramide, sulfatide and ganglioside GM3 were transferred at very slow rates, whereas complex lipids such as gangliosides GM2, GM1 and GD1a were transferred much faster than the former. The transfer rate increased with increasing length of the carbohydrate chain of the lipid molecules. 3. Both the acyl residue in the ceramide moiety and the nature of the carbohydrate chain are significant for recognition of the glycosphingolipids by the sulfatide activator protein. Apparently, both residues serve as an anchor and the longer they are the better they are recognized by the protein. 4. In the absence of activator protein, degradation rates of sulfatide derivatives by arylsulfatase A, and of ganglioside GM1 derivatives by beta-galactosidase, increase with decreasing length of acyl residues in their hydrophobic ceramide moiety. Addition of activator protein stimulates the degradation of only those GM1 and sulfatide derivatives that have long-chain fatty acids in their hydrophobic ceramide anchor. PMID- 1889422 TI - Precision in assessment of osteoporosis from spine radiographs. AB - Inter- and intra-observer variation in spine radiographs of 100 osteoporotic women and longitudinal change in roentgenologic status after 1 year of antiosteoporotic treatment were assessed. The method applied was naked eye inspection, and a score system estimating severity of fractures - vertebral deformation score (VDS). Agreement was assessed by the Kappa coefficient corrected for agreement by change. The results showed a satisfactory inter- and intraobserver agreement for wedge (Kappa = 0.72 and 0.90) and compression fractures (Kappa = 0.60 and 0.92). The method proved less reliable for endplate fractures (Kappa = 0.39 and 0.73). We think that the method of investigation is well suited for monitoring treatment effects in longitudinal studies. PMID- 1889423 TI - Tolerance data of Gd-DTPA: a review. AB - Gd-DTPA is the first paramagnetic contrast agent approved for clinical use in cranial and spinal MRI in the F.R.G., U.S.A., Japan and several other countries. After submission 13,439 patients were enrolled in standardized protocolled clinical trials. The observed adverse drug reactions (ADRs) after i.v. injection of Gd-DTPA were comparable to those after administration of iodinated non-ionic roentgen contrast media (CM). However, the overall incidence of ADRs after intravenous injection of 0.1 or 0.2 mmol/kg body weight Gd-DTPA was found to be even lower. Adverse events were observed in only 1.46% of the patients - or 1.14% if localized warmth is excluded. None of them was critical. There was no correlation between patient age and the incidence of ADRs. In patients with a known history of allergy the incidence of ADRs was increased by a factor 3-4, which is still lower than the incidence reported after intravenous administration of iodinated non-ionic roentgen CM to patients without known allergy. Good renal tolerance was seen in all patients, irrespective of pre-existing renal impairment. Fast bolus injections of Gd-DTPA were tolerated without added risk. The favorable safety profile is also reflected in the post marketing surveillance reports since Gd-DTPA became available as a commercial drug. PMID- 1889424 TI - Are patients with fractures of the femoral neck more osteoporotic? AB - Combined cancellous/cortical density and mass in the femur and lumbar spine were assessed 2 or 3 days after femoral neck fractures and compared to identical measurements in control subjects. Cancellous density was also assessed in the spine. Correction for age differences between patients and controls were made by means of regression analyses and by selecting groups without age differences. After compensation for the age differences, the patients were found to have significantly lower femoral bone mass and lumbar density than the controls. The femoral density and lumbar mass density were not significantly different in the two groups after age correction. The findings for the cancellous spinal density was equivocal. The study indicates that in the femur the total bone mineral content is lower in patients with femur neck fractures and that it is at least one of the etiological factors of these fractures. However, in the femur it is not the bone density that is the decisive factor, but the amount of calcified bone, or the bone mass. PMID- 1889425 TI - MR-imaging with Gd-DTPA in carcinomas of tongue, oro- and hypopharynx. AB - High-field MRI was performed in a series of 24 patients with squamous cell carcinomas of the tongue, oro- and hypopharynx. The value of contrast enhanced T1 weighted images in tumor staging was established prospectively. Non-contrast T1 weighted images did not provide sufficient tumor-delineation. Marked contrast enhancement produced by Gd-DTPA was observed in all carcinomas and in normal pharyngeal mucosa. In tumors of the tongue and upper pharynx clinical examination and ultrasound were equally sensitive as post-contrast MRI; in tumors of the lower pharynx the true tumor extension could be better assessed by contrast enhanced MRI. PMID- 1889426 TI - Postsurgical follow-up of aortic dissections by MRI. AB - Fifteen patients with surgical repair for dissecting aneurysm were examined by Magnetic Resonance Imaging (MRI), using a 0.5 T super-conductive unit. Follow-up studies were obtained at 1 to 18 months (mean 7.2) post-surgery. T1-weighted spin echo sequences were acquired with ECG gating on axial, coronal and oblique sagittal planes. In 6 patients gated gradient rephased sequences were also employed. Residual intimal tear in the native aorta was visualized in 11 patients, together with new or progressive extention of the dissection and aneurysmatic development. Gradient rephasing sequences were useful in detecting slow flow and thrombotic deposits and in evaluating relations to aortic vessels and intimal flap. MR images provided useful information on pathology allowing a non invasive evaluation of the status of the aorta. PMID- 1889427 TI - CT staging of renal carcinoma: a prospective comparison of three dynamic computed tomography techniques. AB - Three dynamic computed tomographic methods used for staging of renal carcinoma in 70 patients are described and compared. Twenty-eight patients were examined using incremental dynamic scanning across the kidneys whilst infusing contrast via an arm vein (technique 1). Eighteen patients were staged using a single location dynamic scan sequence at the level of the renal hilum followed by an incremental sequence during an infusion of contrast into the femoral vein (technique 2). Twenty-four patients were examined using a single location sequence at the level of the renal veins and a rapid bolus incremental dynamic technique (technique 3). Technique 1 correctly staged 20 patients (72%) with 4 patients (14%) understaged and 4 (14%) overstaged, technique 2 correctly staged 11 (61%) patients with 3 (17%) overstaged and 4 (22%) understaged and technique 3 staged 17 (71%) correctly with 3 (13%) understaged and 4 (17%) overstaged. The techniques using single location scanning were more accurate in demonstrating tumour involvement of the renal vein and inferior vena cava but were less accurate in assessing extracapsular spread. Technique 3 was the most accurate in the diagnosis of lymph node involvement. As accurate pre-operative knowledge of vascular involvement by tumour is more important to the surgeon than the presence of extracapsular spread, the combined single location and incremental scan technique is advocated. PMID- 1889428 TI - Correlation between CT and DNA contents in peripheral lung cancers. AB - The DNA contents of 30 lung cancers were correlated with preoperative chest CT findings. Tumors with diameters less than 4 cm had lower DNA contents than larger ones, and tumors with spiculated margins had lower DNA than those with lobulated or smooth margins. As DNA contents are correlated with prognosis, the border configuration of peripheral lung cancers may be enough to predict prognosis. PMID- 1889429 TI - Granulocyte enzymes and complement after an anaphylactoid reaction to coronary angiography. AB - An anaphylactoid reaction following angiography with ioxaglate in a 59-year-old man implied generalized pruritus, angioedema, bronchospasm and hypotension. Leucocytosis and an increased number of neutrophils were observed from 90 min to 8 h after the reaction. Elevated values of the neutrophil specific enzymes elastase and lactoferrin were demonstrated. The concentrations of C3d and CH50 did not change which indicate that no complement activation took place. PMID- 1889430 TI - Peripheral DSA with automated stepping. AB - Peripheral digital angiography can be applied with automated stepping and in digital subtracted technique to evaluate the complete lower extremities angiographically with one single injection of contrast medium. Altogether 25 DSA examinations were compared with non-substracted technique. By DSA-technique additional series could be reduced to only those, where significantly different flow in both extremities necessitated different timing as known from conventional angiography. DSA-technique with automated stepping may in the future totally replace conventional angiography of the peripheral arteries. PMID- 1889432 TI - Splenic lesions: sonographic patterns, follow-up, differential diagnosis. AB - This report concerns 172 patients with sonographically diagnosed benign and malignant splenic lesions. A variety of echopatterns was observed, but a differential diagnosis was often impossible without contributory clinical data. Thirteen patients underwent ultrasound-guided fine-needle biopsy for histological confirmation or therapy. In 14 cases splenectomy was performed for treatment or final diagnosis. Twenty-three patients had malignant space-occupying lesions of the spleen. 26 cases presented with normal splenic size, 47 showed splenomegaly of different extent. Lymphoma was the main basic illness in 60 patients. Thirteen cases presented with splenic metastases from other neoplasms. 71 malignant splenic lesions were hypoechoic when compared with normal splenic echotexture. Only two patients exhibited hyperechoic metastases. In three cases a 'halo' sign was seen. In 99 patients benign focal lesions of the spleen were diagnosed. These included splenic infarction (n = 36), dysontogenetic cysts (n = 23), splenic abscesses (n = 7), splenic calcification (n = 13), and hyperechoic lesions (n = 17) most probably representing splenic hemangioma. PMID- 1889431 TI - ECG changes during cerebral angiography; a comparison of low osmolality contrast media. AB - 334 electrocardiographic recordings obtained from 109 patient who underwent cerebral angiography with low osmolality contrast media (CM) were analysed. CM used in this study included meglumine sodium ioxaglate, iopamidol, and iohexol. A tachycardial effect greater than 10% was seen in 8.3% of recordings, while a bradycardial effect greater than 10% was seen in 11.1%. Assessment was based on the type of CM used, age of the patients, usage of atropine sulfate as premedication, and the vessel injected. Patients who were under 19 years of age, and unpremedicated had a significantly higher incidence of bradycardia. On the other hand, there was no significant difference of the incidence of electrocardiographic abnormality between the three CM, and between two injected vessel groups. We have also analysed the incidence of generalized adverse effect. There was no serious complication, however, 11.9% of the patients who underwent cerebral angiography with ioxaglate developed urticaria and this was significantly higher incidence than in the other two CM groups. PMID- 1889433 TI - Uterine fibromyolipoma: uncommon imaging features. PMID- 1889434 TI - The costal hook: an indicator of occult flail segment in chest trauma. AB - The presence of a hook-like configuration at the site of rib fracture reflects significant rotational displacement. Such displacement can occur only as the result of a further fracture at another site within the same rib and is therefore indicative of a flail segment injury even if a second fracture site is not clearly identified. This appearance is illustrated and termed the 'costal hook' sign. PMID- 1889435 TI - Radiographic reporting directly from the TV monitor of a digital chest radiography system. AB - The practical usefulness of a digital large image intensifier system was tested on 400 consecutive, routine chest examinations. Reading and reporting was carried out directly from the digital images on the TV monitors. For each patient images were also read independently from 100 mm photofluorograms. When the reports for each examination were compared, there was total agreement in reporting in 40% of the cases and clinically insignificant differences in interpretation in 56%. In the remaining 16 patients (4%), the opinion of the observers differed as to whether significant disease was present or not. However, these disagreements could not be related to imaging technique. We believe that a majority of chest examinations can be performed with digital technique and can be read directly from the monitor screen. PMID- 1889436 TI - What is the cost of radiotherapy? PMID- 1889437 TI - The clinical approach--cui bono? PMID- 1889438 TI - First myocardial infarction in smokers. AB - In 484 patients with a first myocardial infarction 155 were smokers at the time of infarction. Their unadjusted survival was superior to the non-smokers at 3 months follow-up, with a relative risk of 0.36 (95% confidence interval 0.22 0.59). Major baseline differences existed between the two populations. When these inequalities were taken into account through a multivariate Cox regression the relative risk was increased to 0.55 (95% confidence interval 0.33-0.93), but was still significantly lower than in non-smokers (P = 0.017). No difference in rate of reinfarction was observed between the two populations. The smokers tended to have a 'less serious infarction' than the non-smokers. However, adding variables that accounted for this into the Cox model did not cancel the impact of smoking. From the results it is suggested that the reduced mortality in smokers is due to a thrombus occurring at an earlier stage of the coronary artery disease. Thus, at the time of infarction smokers' left ventricular function tends to be less affected, and this is reflected in the improved survival rate among smokers in the first months after an acute myocardial infarction. PMID- 1889439 TI - Effects of exercise on the displacement of the atrioventricular plane in patients with coronary artery disease. A new echocardiographic method of detecting reversible myocardial ischaemia. AB - The effect of exercise on the displacement of the atrioventricular (AV) plane was studied by echocardiography (echo) in 48 patients with stable angina pectoris without prior myocardial infarction and 20 age-matched healthy subjects. Echo was performed at rest, immediately after and 10 and 30 min after the test. The patients also underwent thallium stress scintigraphy and coronary angiography. From the apical four- and two-chamber views, the atrioventricular plane displacement (AVPD) during the cardiac cycle was recorded at four sites corresponding to the septal, anterior, lateral and posterior walls of the left ventricle and a mean value was calculated (AV-mean). The healthy subjects and patients had almost the same AVPD at all the sites at rest (AV-mean of 14.5 and 14.2 mm respectively). Immediately post-exercise the healthy subjects showed a significant (P less than 0.001) and equally distributed increase in the AVPD at all the sites with an AV-mean value of 19.2 mm. In most of the patients with angiographically confirmed coronary artery disease (CAD), there was a reversible decrease of AVPD (greater than or equal to 3 mm) at one or more of the AV plane sites. The overall sensitivity and specificity were 80% and 100% respectively in identifying CAD patients. The changes correlated well with the reversible ischaemic changes on the thallium scan (sensitivity, 88%, and specificity, 83%). A generalized exercise-induced decrease in AVPD at all the recorded sites had a high specificity (91%) in detecting patients with three-vessel disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1889440 TI - Prevalence and significance of an abnormal exercise ECG in asymptomatic males. Outcome of thallium myocardial scintigraphy. AB - During a 3-year period 2500 asymptomatic male aviators were screened routinely for coronary artery disease by maximal bicycle exercise testing. In 55 cases (2.1%) the exercise ECG was abnormal (40 subjects exhibited ST depression, 14 ventricular ectopic activity and in one subject both abnormalities were observed). Further non-invasive studies (Thallium scintigraphy, echocardiography and ambulatory ECG monitoring for arrhythmias) identified nine out of the 55 aviators (16%, 95% CL = 7-26%) with an abnormal exercise test as having cardiac disease. We conclude that standard exercise ECG by itself is a poor predictor of coronary artery disease in asymptomatic subjects because of too many false positives when the pre-test likelihood of disease is low. Therefore, exercise electrocardiography cannot be recommended as the single routine screening test for coronary artery disease in such individuals. PMID- 1889441 TI - Role of the electrocardiogram in assessing irreversibly impaired left ventricular systolic function in chronic mitral regurgitation. AB - The study set out to determine whether the electrocardiogram (ECG) might be useful in assessing left ventricular (LV) volumes and systolic function in patients with pure, chronic mitral regurgitation. To do this preoperative haemodynamic and angiocardiographic data, QRS duration, total 12-lead QRS amplitude, R peak time in V6, R peak delay in V6 (RPDV6) (i.e. the R peak in V6 is later than the S peak in V2) and a T wave score assigned to the extent of LV strain were evaluated. Twenty-seven out of 62 patients were subjected to stepwise discriminant multivariate analysis. Radionuclide (RN) LV ejection fraction (EF) was obtained postoperatively; RPDV6, gender, LVEF and LV end-diastolic volume index (EDVI) were selected in decreasing order of discriminatory importance to identify 13 (81.3%) of 16 patients with RNEF greater than or equal to 50% and 10 (90.9%) of 11 with RNEF less than 50% at rest. Preoperatively, 18 subjects with RPDV6 had a significantly greater end-systolic volume index (ESVI) (75.6 +/- 37.8 ml.m-2 versus 50.7 +/- 31.5 ml.m-2, P = 0.003), greater EDVI (196.9 +/- 73.4 ml.m 2 versus 155.2 +/- 48.5 ml.m-2, P = 0.034) and lower LVEF (61.1 +/- 11.9% versus 68.8 +/- 12.7%, P = 0.014) compared to 44 cases without this finding. With respect to postoperative RNEF, eight subjects with RPDV6 had a significantly lower EF compared to 19 cases without this finding (40.1 +/- 8.2% versus 56.0 +/- 9.9%, P = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1889442 TI - Signal averaging of the electrocardiogram in the remote differential diagnosis of broad complex tachycardias. AB - The diagnosis of the origin of a broad complex tachycardia may be difficult, especially in the absence of a 12-lead electrocardiogram of the tachycardia. This study investigates the value of signal averaging in the differential diagnosis of broad complex tachycardia. Signal averaging during sinus rhythm was performed in 102 consecutive patients who presented with broad complex tachycardia (QRS width greater than 110 ms), in whom a definitive electrophysiological diagnosis was made. The presence of late potentials was determined on the basis of two definitions, the second including total QRS duration. The patients studied included 75 with ventricular tachycardia; 33 of these patients had suffered previous myocardial infarction, five had dilated cardiomyopathy, and 37 had a 'normal' heart. Of the 27 patients with supraventricular tachycardia, 22 had an atrioventricular accessory pathway (seven with a delta wave in sinus rhythm), three had atrioventricular nodal tachycardia and two had atrial tachycardia. The sensitivity of late potentials for the diagnosis of ventricular tachycardia was low utilizing both definitions (28% and 45%) although specificity was high (96% and 95%). The sensitivity for the diagnosis of ventricular tachycardia was higher for patients with ischaemic heart disease (43% and 70%) but very low for patients with ventricular tachycardia and a normal heart (16% and 22%). In conclusion, signal averaging in the remote diagnosis of broad complex tachycardia is specific but not sensitive for ventricular tachycardia, which limits its usefulness in selecting patients for electrophysiological study. PMID- 1889443 TI - Morphologic-echocardiographic correlates of Ebstein's malformation. AB - The cross-sectional echocardiographic findings were analysed retrospectively in 26 patients with Ebstein's malformation in the light of studies of autopsied specimens from different patients showing this lesion. The salient anatomical feature in diagnosis is the finding of the hinge point of the septal and mural leaflets of the valve within the inlet component of the right ventricle rather than at the atrioventricular junction. The other important feature is the nature of the distal attachment of the leaflets, particularly the anterosuperior one, which can either be in focal or linear fashion. The hinge point of the septal leaflet was noted echocardiographically to be displaced in 19 patients but, significantly, the leaflet was absent in the other seven. Also significant was that the hinge point of the mural leaflet at the crux had been visualized in only 15 of the patients. The anterosuperior leaflet had a distal linear attachment in 20 of the patients, with the anteroseptal commissure becoming a keyhole in six of these through which blood passed to the functional right ventricle. The valve remained a competent structure, even though closing at the junction of atrialized and functional components of the right ventricle rather than at the atrioventricular junction. Cross-sectional echocardiography is the technique of choice with which to display the salient morphological features of Ebstein's malformation. PMID- 1889444 TI - Clinical and haemodynamic features in relation to severity of aortic stenosis in adults. AB - The main symptoms of aortic stenosis (AS), angina pectoris, dyspnoea, and syncope/effort dizziness, are thought to reflect the severity of AS. This assumption is based on studies in relatively young patients, and may not apply to older age groups. Thus, in 100 consecutive adults (age 41-79 years) referred to cardiac catheterization with suspected AS, clinical and haemodynamic variables were assessed in relation to significant (less than or equal to 0.50 cm2 m-2) (n = 70) and nonsignificant AS (n = 30), and to symptoms. Prevalence of symptoms, functional class, and systolic murmur grade greater than or equal to 3, was similar in the groups. However, patients with significant AS more often had an abnormal second heart sound, electrocardiographic left ventricular (LV) hypertrophy with strain, severe echocardiographic aortic valve calcification, and increased LV wall thickness. Multivariate analysis identified an abnormal second heart sound, and aortic calcification grade, as independent predictors of significant AS. When the Doppler mean gradient was added to the analysis, it became the best predictor. Angina pectoris (n = 74) was related to coronary artery disease, but not to severity of AS. However, 31% of patients without angina also had coronary artery disease. Dyspnoea (n = 69) was only related to age, and syncope/effort dizziness (n = 26) was more frequent in women. Functional class grade was not related to severity of AS. Thus, in adults with assumed symptomatic AS, clinical symptoms do not predict severity of AS. Therefore, the decision for valve replacement should rely on Doppler assessment of the severity of AS. Furthermore, in adults with AS, coronary artery disease cannot be excluded without selective coronary angiography. PMID- 1889445 TI - Acute and long-term efficacy of propafenone in patients with sustained ventricular tachyarrhythmias: assessment with programmed ventricular stimulation. AB - To determine the electrophysiological properties of oral propafenone, 50 patients (39 male and 11 female, aged 31 to 80 years) with sustained ventricular tachycardia or ventricular fibrillation underwent serial electrophysiological drug testing, using propafenone (750 to 900 mg daily) as the anti-arrhythmic regimen of first choice. During baseline study, all patients had inducible sustained ventricular tachyarrhythmias. After oral loading of propafenone, 37 patients (74%) remained inducible whereas 13 were rendered non-inducible. Among the still inducible patients, the mean VT rate decreased from 223 +/- 38 b.min-1 (baseline) to 172 +/- 32 b.min +/- 1 (P less than 0.001). Four patients showed an increase of VT rate during propafenone compared to the VT rate at control. Non inducible patients were discharged on propafenone. During a mean follow-up period of 20 +/- 15 months, there were three non-fatal VT recurrences among the responders, two of them due to non-compliance. Thus, propafenone used as the anti arrhythmic agent of first choice among patients undergoing serial electrophysiological drug testing for ventricular tachyarrhythmias proved effective in suppressing VT induction in 26%. With regard to arrhythmic events, these patients have a favourable outcome. PMID- 1889446 TI - Propofol for direct current cardioversion in cardiac risk patients. AB - We investigated 69 patients (most belonging to NYHA classes II and III) undergoing elective direct current cardioversion of atrial fibrillation (46 patients) and atrial flutter (23 patients), respectively. Without premedication anaesthesia was induced with the new soya bean emulsion of propofol ('Diprivan') 1.2 mg.kg-1 over 45 s. Recovery time was measured from the start of the anaesthetic injection to the moment at which the patients regained consciousness. Completeness of recovery was assessed with two methods: opening eyes on command and time orientation. Good amnesia was observed in all patients. Conversion was achieved in all but seven patients (90%). After injection of propofol, the mean arterial pressure decreased slightly (2% below baseline). Induction of anaesthesia and successful DCC effected a statistically significant decrease in both the heart rate and the rate pressure product. Eleven patients required assisted ventilation for 2 min due to respiratory depression. Fifteen patients developed arrhythmias. Side-effects, such as myocloni, recall or vomiting, were not observed. In conclusion, propofol may well prove to be the anaesthetic of choice for DCC in cardiac patients because of good amnesia, low incidence of side effects and short recovery time (mean 5.3 min). PMID- 1889447 TI - Aortic and coronary atheromatosis in a woman with severe hypercholesterolaemia without LDL receptor alterations. AB - Familial hypercholesterolaemia (FH) is a monogenic disorder, with a strong family history, characterized by a deficiency in functional receptors for low density lipoproteins (LDL). The case of a patient with all the clinical traits of FH, including elevated cholesterol, xanthomas and early coronary and peripheral arterial lesions, but with a normal LDL receptor function, is described. In the patient the molecular weight and immunological properties of apolipoprotein (apo) B were normal; furthermore, autoantibodies to either LDL or to their receptor were also absent. The increased apo B/cholesterol ratio in LDL was compatible with the diagnosis of hyperapobetalipoproteinaemia. With the help of a turnover study using 131I homologous and 125I autologous LDL, it could be established that the patient had an almost three-fold increase in LDL-apo B biosynthesis, with, however, a fractional catabolic rate within normal limits. These findings pointed to the possibility of a genomic alteration in the region responsible for the control of apo B biosynthesis. However, extensive studies both at the cDNA level and in the 5' region of the apo B gene, failed to detect any significant alteration vs published nucleotide sequences. Although the exact mechanism for this unusual clinical presentation of an FH-like syndrome could not be uncovered, this case provides an extreme example of hypercholesterolaemia, with early and severe arterial disease, solely explained by an increased LDL biosynthesis. PMID- 1889448 TI - Dextrocardia, situs inversus and severe mitral stenosis in a pregnant woman: successful closed commissurotomy. AB - A 16-weeks' pregnant woman with situs inversus and dextrocardia underwent successful closed commissurotomy for severe mitral stenosis. The electrocardiogram revealed sinus rhythm with right axis deviation and progressive diminishing of QRS amplitude towards the left precordial leads. The chest X-ray showed dextrocardia with situs inversus. Doppler echocardiography depicted severe mitral stenosis; the mitral valve area increased from 0.9 cm2 pre-operatively to 1.8 cm2 post-operatively with mild increase of mitral regurgitation from grade I to II post-valvotomy. She also had associated mild functional tricuspid insufficiency and moderate pulmonary hypertension. No thrombo-embolic complications occurred intra- or post-operatively. There was no evidence of either clinical or Doppler restenosis. The course of pregnancy was uneventful. At 39 weeks a healthy baby was vaginally delivered. The patient is still free of cardiac symptoms. PMID- 1889449 TI - False tendon rupture simulating chordal rupture after percutaneous mitral balloon dilation. A report of two cases. AB - We describe two cases of ruptured false tendons following percutaneous balloon dilation of the mitral valve in one case, and combined mitral and aortic balloon valvotomy in the other, using in both the retrograde approach. The echocardiographic characteristics of this previously unreported complication of the procedure are presented with special emphasis on the differentiation with true chordal rupture. No short or mid term adverse effects were noted following this complication. PMID- 1889450 TI - Anomalous coronary arteries coursing between the aorta and pulmonary trunk: clinical indications for coronary artery bypass. AB - Coronary arteries of anomalous origin with subsequent coursing between the aorta and pulmonary trunk can cause ischaemia, infarction or sudden death. However, reports of surgical correction are sparse due to the rarity of ante-mortem diagnosis. We report two cases in which symptoms were related to anomalous origin of a non-atherosclerotic coronary artery. Surgical repair was performed to prevent sudden death or recurrent ischaemia. PMID- 1889451 TI - Identification of anomalous origin of one pulmonary artery from ascending aorta by two-dimensional and colour Doppler echocardiography. AB - The anomalous origin of the right pulmonary artery from the ascending aorta in a neonate was diagnosed by two-dimensional and colour directed Doppler echocardiography. An anomalous arterial vessel coursing towards the right lung originated from the posterolateral aspect of the ascending aorta. It could be visualized in parasternal and suprasternal views. The normal bifurcation of the pulmonary trunk was absent. Colour Doppler examination aided in clearer delineation and consequent correct identification of the anomalous vessel as the right pulmonary artery. PMID- 1889452 TI - Prolonged QT, atrioventricular block, and sudden death in the newborn: an electrophysiologic evaluation. AB - An electrophysiologic study was performed in the first month of life in a patient with the congenital long QT syndrome and spontaneous episodes of 2/1 atrioventricular block. The block could be reproduced by incremental atrial pacing, and its infrahisian location was associated with a prolongation of the refractoriness in the ventricular muscle itself. Surprisingly, intravenous propranolol aggravated this phenomenon by further prolonging the QT interval. Sudden death occurred shortly thereafter during Holter monitoring and was due to a sudden resumption of normal AV conduction after an episode of 2:1 block, immediately followed by ventricular fibrillation. PMID- 1889453 TI - Acute natural valve endocarditis due to corynebacterium Group 1 in a normal competent host. PMID- 1889454 TI - Evidence for idiotypic sharing between conventional and naturally activated B cells. AB - In the primary immune response to hen egg-white lysozyme (HEL), approximately 50% of the primary anti-HEL antibody-forming cells (AFC) express IdXE, an idiotype absent from the secondary response. Spontaneous IgM enzyme-linked immunosorbent assay (ELISA)-AFC in spleen cells from naive A/J mice were analyzed for the occurrence of IdXE by use of two affinity-purified rabbit antisera, R213 and R8, each raised against a different primary IdXE+, anti-HEL mAb. Two ELISA-AFC assay methods were used: direct coating of immunoplates with R213 or development of IgM producing ELISA-AFC with biotinylated R8. From ages 7 days until 6 months, 10-20% of spontaneous IgM AFC were found to be IdXE+. IdXE+ anti-HEL IgG1 monoclonal antibodies, 2F4 or 3C11 (100 micrograms/ml), completely inhibited binding of biotinylated R8 (0.5 micrograms/ml) to spontaneous IgM-AFC while IdXE-, anti-HEL IgG1, 5E11 and 2C7, showed no significant inhibition. Greater than 90% of IdXE+ spontaneous IgM-AFC were not HEL specific. We conclude that a dominant set of idiotopes found in a conventional antigen-driven immune response can also play a major role in the spontaneously activated B cell repertoire. Our data argue against a bifurcation of the immune system into a compartment of idiotypic network-related cells and an independent set of non-network cells subject to antigenic stimulation. PMID- 1889455 TI - Monoclonal antibodies that block adhesion of B cell progenitors to bone marrow stroma in vitro prevent B cell differentiation in vivo. AB - B cell differentiation requires adhesion of B cell progenitors to bone marrow (BM) or fetal liver stroma. We show that B lymphoid cells can adhere to the BM stroma cell line CS 1.3, in vitro. Two monoclonal antibodies, SAB-1 and SAB-2, inhibited the adhesion of a B220+ progenitor B cell line but did not interfere with the binding of cytoplasmic mu chain-positive pre-B cells or mature B cells to the BM stromal cell line. Injection of both SAB-1 and SAB-2 antibodies into pregnant mice reduced by 90% the number of B220+n B lineage cells in the livers of their embryos. Livers from such embryos also were virtually devoid of cells able to give rise to B cell colonies in soft agar cultures (CFU-preB). Either antibody separately had no effect. Flow cytometry analysis show that SAB-1 is present on CS 1.3 stroma cells and on a pre-B cell line while SAB-2 is present on pro-B and pre-B cell lines, but not on CS 1.3 stromal cells. SAB-1 and SAB-2 react with different molecules and neither antibody seems to recognize CD44, and adhesion molecule that may also participate in B cell differentiation. Proteinase K and trypsin can digest both SAB-1 and SAB-2 antigens from viable cells suggesting that both are cell surface proteins. We propose that antibodies SAB-1 and SAB-2 probably recognize novel cell-cell adhesion molecules, and that these molecules are involved in the interactions between B cell progenitors and stroma cells. PMID- 1889456 TI - Hemolytic anemia in non-obese diabetic mice. AB - The non-obese diabetic mouse (NOD mouse) is widely used as a model of organ specific autoimmunity because it develops specific autoimmune destruction of pancreatic beta cells mediated by T cells and culminating in insulin-dependent diabetes mellitus. Here, we report that the NOD mouse also develops Coombs' positive hemolytic anemia, a B cell-mediated autoimmune disease. Aged NOD mice were found to have splenomegaly and jaundice predominantly due to raised unconjugated serum bilirubin. Their hematocrits were markedly lowered, and there was a reciprocal increase in the reticulocyte count. Red blood cells (RBC) from anemic mice showed a normal lytic response to hypotonicity. RBC from non-anemic mice had normal half lives in non-anemic, non-diabetic NOD mice by 51Cr labeling but, dramatically shortened half lives in anemic mice. Similar results were obtained with RBC from anemic mice. Hemolysis could be transferred with serum from anemic mice resulting in reticulocytosis. The antibody-mediated nature of the anemia was confirmed with the direct Coombs' test. Anemia was found only in mice aged greater than 200 days and was more common in diabetic (4/8) than non diabetic (1/16) mice at 300 days. However, by 550 days, 14/17 non-diabetic mice were affected. PMID- 1889457 TI - Tolerance to a self peptide from the third hypervariable region of the Es beta chain. Implications for molecular mimicry models of autoimmune disease. AB - As a first step in the analysis of a molecular mimicry model of rheumatoid arthritis, we addressed the question of whether tolerance to self-major histocompatibility complex (MHC) class II molecules includes tolerance to peptides from the third hypervariable region of their beta chain. We studied T cell responses to a peptide from the third hypervariable region of the Es beta chain, Es beta peptide (PEFLEQRRAAVDTYC), in different mouse strains after footpad priming with peptide in complete Freund's adjuvant. Strains of mice of the k or d haplotype (B10D2; H-2d, B10BR; H-2k) mounted a vigorous T cell response to the Es beta peptide. In mice expressing the Es beta chain either on the cell surface (B10S9R) or in the cytoplasm as free unassociated chain (B10S), no response could be detected. Binding studies using purified MHC class II molecules and competition for antigen presentation showed that the Es beta peptide binds Ak, Ad and As but not Ek. Thus, the nonresponder status of B10S and B10S9R mice appears to reflect self tolerance. Tolerance was also suggested by the observation that responder x nonresponder F1 crosses such as (B10D2 x B10S9R) and (B10BR x B10S9R) did not respond to Es beta peptide. Interestingly, mice derived from the (B10BR x B10S) cross responded to the Es beta peptide, suggesting that the immune system may not always tolerate peptides from the third hypervariable region of self-MHC class II molecules. PMID- 1889458 TI - The binding affinity and dissociation rates of peptides for class I major histocompatibility complex molecules. AB - Peptides of various lengths derived from the influenza nucleoprotein (NP) bind to H-2Db class I molecules with affinities at 4 degrees C between approximately 3 x 10(5)- approximately 3 x 10(7) M-1. The peptide with the highest affinity corresponds to the sequence of nine amino acids (NP366-374) recently isolated from cells infected with influenza. This peptide forms stable complexes with half lives greater than 110 h at 4 degrees C, 39 h at 22 degrees C and 3 h at 37 degrees C. Small increases in length of the peptide greatly reduce the stability of the complex (t1/2 approximately 1-10 h at 4 degrees C). These results may explain the homogeneous length of peptides isolated from class I molecules formed in vivo, and suggest that class I and II may differ in their dependence on the length of peptides for the formation of stable complexes. PMID- 1889459 TI - The early cellular and humoral immune response to primary and booster oral immunization with cholera toxin B subunit. AB - The immune response to cholera toxin B subunit given orally was studied in 13 human volunteers. A serum IgG and IgA antitoxin response was observed, which was boosted by a second immunization. Using an immunospot assay, cells spontaneously secreting anti-toxin IgG and IgA, but not IgM appeared transiently in the blood after immunization. There were 105 IgG- and 87 IgA-secreting cells per 2 x 10(6) mononuclear cells 7 days after the first immunization, and 282 IgG- and 413 IgA secreting cells 5 days after the second immunization. A polyclonal increase in total IgM-secreting cells was observed. Few anti-toxin-secreting cells were observed in the bone marrow at the peak of the circulating cell response, which could be accounted for by contamination of the sample with peripheral blood, suggesting that the bone marrow is not a significant site of anti-toxin-secreting cells after oral immunization. PMID- 1889460 TI - Homotypic aggregation of human cell lines by HLA class II-, class Ia- and HLA-G specific monoclonal antibodies. AB - Major histocompatibility complex (MHC) class II molecules have been implicated in cell adhesion in two ways. In addition to the well-established role of class II antigens in low-affinity adhesion provided by interactions between class II and CD4, recent data indicated that class II may also induce adhesion between T and B cells by activating the CD18/CD11a (LFA-1) adhesion pathway. Here we report that monoclonal antibodies (mAb) against HLA-DR (L243, p4.1, HB10a, VI15) and certain broad class II reacting mAb (TU35, TU39), but not anti-DQ (TU22, Leu-10) mAb, induced homotypic aggregation of human class II-positive monocytic (I937) and T leukemic (HUT78) tumor cell lines and Epstein-Barr virus (EBV) transformed B lymphoid cell lines (EBV-LCL). Class II-negative cell lines (U-937 and the EBV LCL mutant line 616) were not induced to aggregate. An HLA-G-transfected EBV-LCL, 221-AGN, but not the class I-negative parental line, 221, showed homotypic aggregation in response to an HLA-G specific mAb (87G) and a broad reacting class I-specific mAb (IOT2). Both cell lines responded with aggregation to anti-class II mAb (TU35). The anti-class I mAb, W6/32, had no effect on all cell lines tested and two anti-beta 2-microglobulin mAb had variable, weak effects. The aggregation response was an active, temperature-sensitive process which was almost totally abrogated by azide and by cytochalasins B and E, but unaffected by colchicine, EDTA, aphidicolin, actinomycin D and protein tyrosine kinase inhibitors (genistein, herbimycin A). Serine/threonine protein kinase inhibitors (staurosporin, H7) partly inhibited the aggregation responses. There was no strict correlation between induction of aggregation and epitope density. FcR were not involved in the aggregation response, since F(ab')2 fragments of anti-DR mAb, L243, were as effective as the whole antibody. The aggregation was not influenced by mAb against accessory molecules previously shown to be involved directly or indirectly in homotypic aggregation [CD11a (LFA-1)/CD18/CD54 (ICAM-1), CD58 (LFA 3)/CD2, BB1/CD28, CD43, and CD44]. In conclusion, these data provide further evidence that HLA molecules are implicated in a novel, cellular aggregation phenomenon involving the cytoskeleton. PMID- 1889461 TI - Molecular cloning of cDNAs for the rat interleukin 2 receptor alpha and beta chain genes: differentially regulated gene activity in response to mitogenic stimulation. AB - We have isolated, by transient expression and screening using an oligonucleotide probe, cDNA clones encoding the rat interleukin 2 receptor (IL 2R) alpha and beta chains, respectively. Both chains are approximately 60% identical at the amino acid level to their human counterparts. In common with the human and mouse IL 2R beta chains, the rat beta chain is a member of the cytokine receptor family. The rat IL 2R beta chain contains no conventional signal transduction machinery and, like the mouse IL 2R beta chain, has a significant number of deletions in its cytoplasmic tail in comparison to the human protein. Northern analysis indicates that the rat beta chain message is constitutively transcribed in normal resting lymphocytes, whereas the alpha chain message is absent. Transcription of both chains of the receptor is up-regulated by cellular activation. However, kinetic studies have shown that whereas alpha chain message is rapidly induced, and can be detected 5 h after the addition of phytohemagglutinin, levels of beta chain mRNA increase at a much later time point and are not seen to rise until approximately 24 h after the addition of mitogen. These data suggest that the expression of high-affinity IL 2R is controlled by factors which influence transcription of both the alpha and the beta chain genes. PMID- 1889462 TI - Dissociation between plasma and monocyte-associated cytokines during sepsis. AB - We report our investigations of circulating interleukin (IL) 1 beta, IL 6 and tumor necrosis factor (TNF)-alpha, as well as cell-associated IL 1 alpha, IL 1 beta and TNF-alpha in plasma and monocytes of 21 patients with sepsis syndrome and 6 patients with non-septic shock. Longitudinal studies reveal that (a) the most frequent detectable plasma cytokines were TNF-alpha and IL 6, (b) the presence and the kinetics of circulating cytokines were independent of one other, (c) detectable levels of cytokines could be found for a long period of time, and (d) significantly higher levels of IL 6 were found for non-surviving patients. Because of the in vivo half-life of cytokines and of the existence of numerous specific high-affinity receptors, it is quite probable that detectable plasma cytokines represent the excess of produced mediators which have not been trapped by the target cells. TNF-alpha (410 +/- 65 pg/10(6) monocytes) and IL 1 beta (153 +/- 60 pg/10(6) monocytes) were frequently found associated to monocyte lysates (88% and 50%, respectively). Despite the fact that IL 1 alpha is the most abundant cytokine found associated to monocytes following in vitro activation, IL 1 alpha was rarely found in monocytes of intensive care unit patients (29%). No correlation was found to exist between the levels of plasma cytokines and cell associated cytokines. Some patients had plasma TNF-alpha or IL 1 beta in the absence of the corresponding monocyte-associated cytokine. This observation suggests that cells other than monocytes can participate in the production of circulating cytokines. At the end of the longitudinal study (day 14 +/- 2), only 2/12 surviving patients still had plasma TNF-alpha, whereas 8/12 had monocyte associated TNF-alpha. These results indicate that activation of monocytes still occurs in patients for whom no plasma cytokines can be detected. Thus, in addition to the measurement of plasma cytokine, measurement of cell-associated cytokine appears useful to assess cytokine production and monocyte activation in vivo. PMID- 1889463 TI - Expansion and high proliferative potential of the macrophage system throughout life time of lupus-prone NZB/W and MRL lpr/lpr mice. Lack of down-regulation of extramedullar macrophage proliferation in the postnatal period. AB - Systemic lupus erythematosus is an autoimmune disease, characterized by high titers of autoantibodies against many cell-membrane and intracellular antigens. Polyclonal B cell activation and alterations in the T cell compartment have been described. The present report deals with the organ-associated macrophage (M phi) system of two lupus-prone mouse strains (NZB/W and MRL lpr/lpr) and demonstrates that in both mouse strains the M phi compartment of liver and spleen is clearly expanded. In the liver the number of F 4/80+ M phi is strongly elevated. In addition, presence of early M phi precursors and of extramedullary organ associated monocyte proliferation in response to colony-stimulating factor (CSF) is documented in liver and spleen of these mice. Further, in normal animals during the first two weeks of life extramedullar monocytopoiesis is present in liver and spleen, which is then down-regulated in the third week of life. In the two lupus-prone mouse strains down-regulation does not occur but extramedullar monocyte proliferation is sustained at high level throughout life time. As possible correlates for the expansion of the M phi system elevated CSF-1 mRNA levels are demonstrated in kidney, spleen and liver of NZB/W mice and elevated CSF serum levels are documented in MRL lpr/lpr mice. The possible contribution of the expanded M phi system to B and T cell dysregulation is discussed. PMID- 1889464 TI - Coordinate secretion and functional synergism of T cell-associated serine proteinase-1 (MTSP-1) and endoglycosidase(s) of activated T cells. AB - Cell lysates and exocytosed soluble mediator(s) (ESM) released from CD8+ T cell lines (TCL) by receptor-triggered secretory exocytosis were tested for degradation of proteoglycans associated with in vitro produced subendothelial extracellular matrix (ECM). ESM was found to release low-molecular weight (kav 0.5-0.6) fragments from the sulfated proteoglycans in ECM. In the presence of heparin, an inhibitor for endoglycosidase activity, only high-molecular-weight products (kav 0.2) were formed. Preincubation of ESM with HD-prolylphenylalanyl arginyl-chloromethylketone (PFR-CK) an inhibitor for the T cell-associated serine proteinase-1 (MTSP-1) totally prevented release of high- and low-molecular weight proteoglycan fragments. Furthermore, it was shown that purified MTSP-1 is able to release from ECM high-molecular weight proteoglycans and that this process is inhibitable by PFR-CK but not by heparin. Further treatment of these soluble high molecular weight sulfated proteoglycans with ESM from TCL 1.D9 led to appearance of low-molecular weight split products (kav 0.5-0.6). This conversion was inhibitable by heparin but not by PFR-CK. These findings indicate that activated T cells contain two enzymatic activities, i.e. MTSP-1 and at least one endoglycosidase, which after receptor-triggered secretion can synergize in the degradation of sulfated proteoglycans in subendothelial ECM. PMID- 1889466 TI - Negative signaling by surface IgM on B cells isolated from ileal Peyer's patch follicles of sheep. AB - Lymphoid follicles from the sheep ileal Peyer's patch (PP) were used to prepare a cell suspension consisting of 98% surface IgM-positive (sIgM+) B cells and 1% T cells. Co-stimulation of follicular cells with pokeweed mitogen and either recombinant bovine interleukin 1 (IL 1) or IL 2 resulted in a marked proliferative response. In contrast, the addition of soluble F(ab')2 rabbit anti sheep Ig completely inhibited the proliferative response induced by pokeweed mitogen and IL 1 or IL 2 co-stimulation. Anti-Ig inhibition of B cell proliferation was specific for ileal PP follicular cells and was not observed with mesenteric lymph node cells or splenocytes. Furthermore, suppression of ileal PP follicular B cell proliferation required at most divalent cross-linking of sIg was independent of Fc receptors, but was dependent on the concentration of anti-Ig and required 48 h for maximal effect. Negative signaling by sIgM indicates that ileal PP follicular B cells are functionally distinct from B cells in other secondary lymphoid tissues. Also, the present observations are consistent with previous reports indicating that B cell proliferation in ileal PP follicles is antigen independent. PMID- 1889465 TI - Lack of H-2 restriction of the Plasmodium falciparum (NANP) sequence as multiple antigen peptide. AB - The major surface antigen of malaria sporozoites, the circumsporozoite protein, contains a region of tandem amino acid repeats, which in the case of the human malaria parasite Plasmodium falciparum, consist of four amino acids Asn-Ala-Asn Pro (NANP) repeated up to about 40 times. This repetitive sequence has been considered as the basis for the development of subunit vaccines against P. falciparum malaria. We and others had previously shown that synthetic and recombinant NANP peptides were immunogenic only in H-2b mice. In the present report we show that, when mice with different H-2 haplotypes are immunized with the repetitive NANP sequence incorporated in a synthetic branching multiple antigen peptide (MAP), all except one of the mouse strains tested mounted an anti peptide antibody response. Such a response does not appear to be due to the peculiar assembly of the NANP sequence. In fact, MAP containing repetitive sequences from circumsporozoite proteins of other malaria parasites did not overcome the genetic restriction of the immune response to the linear peptides. These data show that in the case of the P. falciparum NANP repeats, their immunogenicity can be dramatically changed and increased when these peptides are assembled as MAP. This unexpected finding may be of interest in the design of synthetic candidate malaria vaccines. PMID- 1889467 TI - Exogenous beta 2-microglobulin is required for antigenic peptide binding to isolated class I major histocompatibility complex molecules. AB - Binding of antigenic peptides to purified class I major histocompatibility complex (MHC) molecules, as measured by antigen-specific cytolytic T lymphocyte (CTL) degranulation, was found to occur in the presence of serum but not in its absence. The role of soluble beta 2-microglobulin (beta 2m), a normal component of serum, in class I-peptide complex formation was therefore examined. Sera depleted of beta 2m did not support effective peptide binding to class I, but binding was restored in the presence of low concentrations of purified human beta 2m. Sequential incubation of immobilized class I with human beta 2m first, followed by peptide, resulted in antigenic complex formation, while reversing the order of pulsing could not. Similar results were obtained in experiments examining H-2Db, Kb and Kd with appropriate peptides and CTL. These results demonstrate that mature class I proteins are not able to directly bind peptide, but that interaction with exogenous beta 2m results in a structure that will subsequently bind peptide. Binding of exogenous beta 2m appears to result in "empty" class I molecules, possibly by exchange for endogenous beta 2m, with a concomitant loss of endogenous peptide. PMID- 1889468 TI - T cell function in patients with impaired antibody responses to polysaccharide antigens. PMID- 1889469 TI - Schistosoma haematobium and S. japonicum: analysis of the ribosomal RNA genes and determination of the "gap" boundaries and sequences. AB - We have determined the intragenic organization of the rRNA genes of Schistosoma haematobium and S. japonicum and found them to be similar to that of S. mansoni and other eukaryotes. An entire ribosomal repeat approximately 10 kbp in size from each species was isolated as a SalI fragment from a genomic library constructed in bacteriophage lambda. The segments encoding both the small and large rRNAs have been identified using three cloned EcoRI fragments of S. mansoni as probes. There were three EcoRI fragments (4.2, 3.0, 1.6 kbp) from S. haematobium and four EcoRI fragments (4.6, 2.3, 1.7, 1.0 kbp) from S. japonicum. As in a wide variety of organisms within the protostome phyla, the 28S rRNA in schistosomes contains a "gap" which separates it into two fragments. The length of the gap sequence in S. haematobium is 54 bases and it is identical to that in S. mansoni in both length and sequence. However, in S. japonicum the sequence is between 64-67 bases long. In each case, irrespective of the species, the gap is located at the same position within the 28S rRNA. Secondary structures of the gap sequence derived by computer analysis predict a conformation with the minimum free energy that has an UAAU tract in a hairpin loop for S. haematobium and an UAUU tract for S. japonicum. PMID- 1889470 TI - Trichinella spiralis: a 76-kDa excretory/secretory larval antigen identified by a monoclonal antibody. AB - Spleen cells from BALB/c mice were fused with myeloma cells following infection of the mice with Trichinella spiralis larvae and an ip booster injection with larval homogenate antigen. A monoclonal antibody (Mab), designated as TS 3G6 which did not react with sera or tissue extracts from noninfected mice, rats, and guinea pigs, was selected for further studies because of its high activity and specificity. When tested in ELISA TS 3G6 did not cross-react with Ascaris suum, A. lumbricoides, Toxocara canis, E. granulosus (larvae), Trichiuris suis, or T. ovis. Western blot analysis showed that Mab 3G6 recognized an antigen of 76 kDa located in the stichosome of the larvae as well as on the surface of the larval cuticle. Digestion of a larval extract with different enzymes suggests that the Mab TS 3G6 corresponding epitope is a polypeptide. The TS 3G6 antigen was detected in culture supernatants of Trichinella muscle larvae and in sera of experimentally infected animals using a sensitive ELISA assay. This secretory antigen also seemed to induce a specific immune response in the host since sera from infected animals could block the binding of Mab TS 3G6 to its target antigen when tested in a competitive ELISA. PMID- 1889471 TI - Interaction of the 140/130/110 kDa rhoptry protein complex of Plasmodium falciparum with the erythrocyte membrane and liposomes. AB - During Plasmodium falciparum merozoite invasion into human and mouse erythrocytes, a 110-kDa rhoptry protein is secreted from the organelle into the erythrocyte membrane. In the present study our interest was to examine the interaction of rhoptry proteins of P. falciparum with the erythrocyte membrane. It was observed that the complex of rhoptry proteins of 140/130/110 kDa bind directly to a trypsin sensitive site on intact mouse erythrocytes, and not human, saimiri, or other erythrocytes. However, when erythrocytes were disrupted by hypotonic lysis, rhoptry proteins of 140/130/110 kDa were found to bind to membranes and inside-out vesicles prepared from human, mouse, saimiri, rhesus, rat, and rabbit erythrocytes. A binding site on the cytoplasmic face of the erythrocyte membrane suggests that the rhoptry proteins may be translocated across the lipid bilayer during merozoite invasion. Furthermore, pretreatment of human erythrocytes with a specific peptide derived from MSA-1, the major P. falciparum merozoite surface antigen of MW 190,000-200,000, induced binding of the 140/130/110-kDa complex. The rhoptry proteins bound equally to normal human erythrocytes and erythrocytes treated with neuraminidase, trypsin, and chymotrypsin indicating the binding site was independent of glycophorin and other major surface proteins. The rhoptry protein complex also bound specifically to liposomes prepared from different types of phospholipids. Liposomes containing PE effectively block binding of the rhoptry proteins to mouse cells, suggesting that there are two binding sites on the mouse membrane for the 140/130/110-kDa complex, one protein and a second, possibly lipid in nature. The results of this study suggest that the 140/130/110 kDa protein complex may interact directly with sites in the lipid bilayer of the erythrocyte membrane. PMID- 1889472 TI - Trichinella spiralis: light microscope monoclonal antibody localization and immunochemical characterization of phosphorylcholine and other antigens in the muscle larva. AB - A panel of monoclonal antibodies was used to examine the structure of the muscle larva of Trichinella spiralis under the light microscope. Immunofluorescence and, in some cases, immunoperoxidase staining were used. All four antibodies reacted with the cuticle of the organism, although differences in the staining pattern were observed for some of these. Interestingly, all the antibodies also reacted with the stichosome. One of the antibodies (Ts2Ab) is specific for the hapten, phosphorylcholine. In a binding assay, this antibody also reacted with extracts of Trichuris suis, Ascaris suum, and Fasciolopsis buski, but not with extracts derived from Cysticercus cellulosae, Candida albicans, Salmonella typhi, or Escherichia coli. This crossreactivity was confirmed microscopically in which the cuticle, oviduct and eggs of T. suis, the cuticle, muscle cells, and eggs of A. suum, and the cuticle and vitelline glands of F. buski were seen to be clearly stained by the antibody. In addition, Ts2Ab also reacted with the cuticle and stichosome of the adult T. spiralis worm. In Western blot analysis, Ts2Ab recognized a 43-kDa antigen from T. spiralis muscle larvae extracts, while a previously studied antibody (7C2C5Ab) identified four major antigens (48.5, 47, 43, and 39 kDa) in this preparation. Similar results were obtained when the 24-hr excretory-secretory (ES) antigens of T. spiralis were immunoblotted with the antibodies, although the reactivity shown by Ts2Ab was relatively weak. With the 72-hr ES material, on the other hand, major antigens of lower mol wt (44, 28, and 25 kDa) were revealed by 7C2C5Ab, and no reactivity was seen with Ts2Ab. However, this antigen preparation reacted well with both antibodies in an enzyme-linked immunoassay. Taken together, the findings suggest that the 72-hr ES antigens probably result from extensive degradation of material originally secreted or excreted by the worm. Similar binding studies on the 24-hr ES preparation indicated that this source may be relatively rich in 7C2C5Ab-reactive epitopes and relatively poor in the antigen identified by Ts2Ab. Other studies performed demonstrated that the antigens recognized by these two antibodies were distinct and physically unassociated. PMID- 1889473 TI - Acanthocheilonema viteae: vaccination of jirds with irradiation-attenuated stage 3 larvae and with exported larval antigens. AB - Jirds (Meriones unguiculatus) were immunized with irradiated (35 krad) stage-3 larvae (L3) of Acanthocheilonema viteae. The induced resistance against homologous challenge infection and the antibody response of the animals were studied. Immunization with 3, 2, or 1 dose of 50 irradiated L3 induced approximately 90% resistance. Immunization with a single dose of only 5 irradiated L3 resulted in 60.8% protection while immunization with a single dose of 25 L3 induced 94.1% protection. The protection induced with 3 doses of 50 irradiated L3 did not decrease significantly during a period of 6 months. Sera of a proportion, but not all resistant jirds, contained antibodies against the surface of vector derived L3 as defined by IFAT. No surface antigens of microfilariae or adult worms were recognized by the sera. Vaccinated animals had antibody responses against antigens in the inner organs of L3 and in the cuticle and reproductive organs of adult worms as shown by IFAT. Immunoblotting with SDS PAGE-separated L3 antigens and L3-CSN revealed that all sera contained antibodies against two exported antigens of 205 and 68 kDa, and against a nonexported antigen of 18 kDa. The 205-kDa antigen easily degraded into fragments of 165, 140, 125, and 105 kDa which were recognized by resistant jird sera. Various antigens of adult worms, but relatively few antigens of microfilariae, were also recognized. To test the relevance of exported antigens of L3 to resistance, jirds were immunized with L3-CSN together with a mild adjuvant. This immunization induced 67.7% resistance against challenge infection and sera of the immunized animals recognized the 205- and 68-kDa antigens of L3. PMID- 1889474 TI - Interaction of benzimidazole anthelmintics with Haemonchus contortus tubulin: binding affinity and anthelmintic efficacy. AB - The ability of various benzimidazoles (BZs) to bind tubulin under different conditions was assessed by determining their IC50 values (the concentration of unlabeled drug required to inhibit 50% of the labeled drug binding), Ka (the apparent equilibrium association constant) and Bmax (the maximum binding at infinite [BZ] = [drug-receptor]). The ability of unlabeled benzimidazoles- fenbendazole, mebendazole (MBZ), oxibendazole (OBZ), albendazole (ABZ), rycobendazole (albendazole sulfoxide, ABZSO), albendazole sulfone, oxfendazole (OFZ), and thiabendazole--to bind tubulin was determined from their ability to inhibit the binding of [3H]MBZ or [3H]OBZ to tubulin in supernatants derived from unembryonated eggs or adult worms of Haemonchus contortus. The binding constants (IC50, Ka, and Bmax) correlated with the known anthelmintic potency (recommended therapeutic doses) of the BZ compounds except for OFZ and ABZSO whose Ka values were lower than could be expected from anthelmintic potency. The binding of [3H]ABZ or [3H]OFZ to tubulin in supernatants derived from BZ-susceptible and BZ resistant H. contortus was compared. [3H]ABZ demonstrated saturable high-affinity binding but [3H]OFZ bound with low affinity. The high-affinity binding of [3H]ABZ was reduced for the R strain. Tubulin bound BZ drugs at 4 degrees C with lower apparent Ka than at 37 degrees C. PMID- 1889475 TI - The effector function of nitrogen oxides in host defense against parasites. PMID- 1889476 TI - Enhancement of the antimalarial effect of chloroquine on drug-resistant parasite strains--a critical examination of the reversal of multidrug resistance. PMID- 1889477 TI - Relationship between platelet volume and anti-platelet autoantibodies in idiopathic thrombocytopenic purpura. AB - We used flow cytometry to explore the relationship between platelet volume and anti-platelet autoantibodies in 71 patients with idiopathic thrombocytopenic purpura (ITP). An increase in platelet volume was found more frequently in patients with a platelet count of less than 20,000/microliters. Platelet volume was larger in patients without anti-GPIIb/IIIa autoantibodies than in patients with these autoantibodies. Furthermore, the platelet count was significantly lower in patients without anti-GIIb/IIIa autoantibodies than in the patients with these autoantibodies. There was a positive correlation between a large platelet volume in patients with a platelet count of less than 30,000/microliters and high platelet-associated IgM levels. These results suggest that the platelet volume is related to the severity of thrombocytopenia in ITP. PMID- 1889478 TI - Folate-deficient human lymphoblasts: changes in deoxynucleotide metabolism and thymidylate cycle activities. AB - Peripheral blood lymphocytes of healthy volunteers cultured with phytohaemagglutinin in folate-deficient medium exhibit megaloblastic maturation with reduced intracellular folate content. We have employed this in vitro model for megaloblastic maturation to determine accompanying changes in cellular thymidylate cycle activities and deoxynucleotide levels. Folate-deficient cells exhibit a two-fold increase in thymidine kinase and thymidylate synthase activities. These increased activities were reduced to those of folate-replete cells by co-culture of folate-deficient cells with thymidine. Folate deficiency was accompanied by reduced cellular levels of thymidine triphosphate (TTP) and deoxyguanosine triphosphate (dGTP). Exogenous deoxyuridine produced no increase in the reduced levels of TTP of folate-deficient cells but effected a two-fold increase in cellular deoxycytidine triphosphate. Exogenous thymidine increased the reduced TTP levels of folate-deficient cells and corrected the reduced dGTP level; the increase in cellular TTP accompanying exogenous thymidine was more pronounced in folate-deficient cells. These in vitro findings are compatible with a block in de novo thymidylate synthesis and explain in part the reported in vivo changes for the deoxynucleotide pool in megaloblastic marrow cells due to folate or vitamin B12 deficiency. PMID- 1889479 TI - Dietary deficiency of vitamin B12 is associated with low serum cobalamin levels in non-vegetarians. AB - A prospective study of 106 patients with low serum cobalamin (vitamin B12) levels showed that, in 37, it was unexplained. The dietary intake of the vitamin was assessed in these patients by questionnaire and was found to be low in 10 (37%). None of these patients was vegetarian and they were of varying age and social circumstance. Dietary deficiency may be the sole cause of a low serum cobalamin in a significant proportion of non-vegetarians. An assessment of dietary intake should be part of the investigation of cobalamin deficiency. PMID- 1889480 TI - Acute renal failure associated with haematological malignancies: a review of 10 years experience. AB - Patients with ARF and haematological malignancy (excluding myeloma), presenting to a single unit over 10 years were analyzed to see if patients likely to benefit from intensive renal supportive therapy could be identified. 31 episodes of ARF were identified in 29 patients (mean age 51 +/- 2.9 yr): 19 were associated with acute leukaemia (13 AML, 6 ALL); 10 with lymphoma. Acute tubular necrosis (ATN) was identified as the cause of ARF in 26 cases, with sepsis (96%) and exposure to nephrotoxic drugs (88%), especially aminoglycosides, being the commonest precipitating factors. Toxic levels of the latter were commonly documented. Patient survival was 45%. Requirement for mechanical ventilation resulted in a universally fatal outcome; age greater than 55 yr and the presence of CNS symptoms or signs were also significantly associated with a poor outcome. Non-ATN causes (urate nephropathy or obstruction) carried a better prognosis. However, only 4 patients (14%) lived for more than 6 months following ARF. Thus, although a subgroup of patients more likely to benefit from treatment can be identified, the overall prognosis is poor and limited by that of the underlying disease. The potential benefit of avoiding nephrotoxic drugs, especially aminoglycosides, in these patients is highlighted by this study. PMID- 1889481 TI - Influence of blood donation on iron stores assessed by serum ferritin and haemoglobin in a population survey of 1433 Danish males. AB - The general impact of blood donation on iron status has been studied in Danish males. Iron stores were assessed by serum (S-) ferritin and haemoglobin (Hb) in a population survey comprising 1433 males in age cohorts of 30, 40, 50, and 60 years; 389 (27%) were blood donors and 1044 (73%) non-donors. Hb levels were identical in donors and non-donors, mean 155 +/- 11 (SD) g/l (9.6 +/- 0.7 mmol/l); values less than 129 g/l (8.0 mmol/l) were observed in 1.3% of donors vs 1.9% of non-donors. Correlations between S-Ferritin and Hb were slight and without practical clinical relevance: rS = 0.13, p less than 0.01 in donors vs rS = 0.16, p less than 0.0001 in non-donors. Donors had lower S-Ferritin, median 95 micrograms/l, than non-donors, median 136 micrograms/l (p less than 0.0001). S Ferritin values less than 15 micrograms/l (i.e. depleted iron stores) were seen in 3.3% of donors vs 0.4% of non-donors, and S-Ferritin values of 15-30 micrograms/l (i.e. small iron stores) in 9.8% of donors vs 1.4% of non-donors. Iron-deficiency anaemia (i.e. S-Ferritin less than 15 micrograms/l and Hb less than 129 g/l) was seen in 0.26% of donors vs 0.10% of non-donors; employing the 5th percentile for Hb (137 g/l (8.5 mmol/l] as discriminatory value increased the percentage of iron-deficiency anaemia to 0.51% in donors vs 0.10% in non-donors. Blood donation had a marked influence on iron status in the adult male population. The frequency of phlebotomy should be adjusted according to S Ferritin as well as Hb levels. If Hb is used as single criterion for donation, only donors with pre-donation values greater than or equal to 135-137 g/l should be allowed phlebotomy. Optimal donation standards should include monitoring of iron status through measurement of S-Ferritin and Hb, combined with individualised postdonation iron supplementation. PMID- 1889482 TI - Expression of cell surface transferrin receptor and intracellular ferritin after in vitro stimulation of peripheral blood T lymphocytes. AB - Measurements of peripheral blood lymphocyte surface transferrin receptor using flow cytometry show that phytohaemagglutinin (PHA) stimulation causes a marked increase in both the number of cells bearing receptors and the absolute number of receptors. This increase is accompanied by the interleukin-2 receptor and there is a progressive increase of cells in the S phase of their cycle. Furthermore, ferritin synthesis in proliferating cells, as determined by immunoprecipitation techniques, increases significantly compared to non-stimulated cells. Intracellular concentrations of both spleen-type and heart-type ferritin are also increased with a preferentially high proportion of heart-type ferritin. These results suggest that expression of transferrin receptor and synthesis of ferritin is regulated by a complex mechanism. Cellular proliferative activity increases the expression of transferrin receptor and could modulate the biosynthesis of intracellular ferritin that is normally controlled by iron. These two processes do not appear to be linked. PMID- 1889483 TI - Exchange transfusion in the neonate, a comparison between citrate-, heparinized- and reconstituted whole blood. PMID- 1889484 TI - Meperidine (pethidine) to control shaking chills and fever associated with non hemolytic transfusion reactions. PMID- 1889485 TI - Coexistence of myelofibrosis and focal osteolysis with clusters of megakaryocytes and necrosis in a patient with trilineage myelodysplastic syndrome. PMID- 1889486 TI - Changes in serum erythropoietin levels during allogeneic bone marrow transplantation. AB - Serial serum erythropoietin levels were measured in 10 consecutive patients undergoing allogeneic bone marrow transplantation. Observed erythropoietin levels are compared with those predicted from a large control population of anaemic patients not receiving chemotherapy. There was an initial acute rise in serum erythropoietin, peaking between days 1 and 4 after marrow transfusion, which was unrelated to changes in haemoglobin concentration. Patients maintained serum erythropoietin concentrations at around twice the predicted level for the first 2 weeks following transplantation, with a gradual fall into the expected range by wk 3. Erythropoietin levels did not change with episodes of bacterial infection or acute graft-versus-host disease. A patient with severe aplastic anaemia had initial successful engraftment with normalisation of erythropoietin levels, but showed a marked and amplified rise in erythropoietin 2 wk before falling peripheral blood counts indicated failure of the bone marrow graft. PMID- 1889487 TI - In vivo evaluation of the anemia induced by azidothymidine (AZT) in a murine model of AIDS. AB - Azidothymidine (AZT) induces severe anemia in patients with acquired immune deficiency syndrome (AIDS). To evaluate the mechanism of anemia in immune suppressed animals, a murine model of AIDS (MAIDS), caused by infection with LP BM5 murine leukemia virus (LP-BM5 MuLV) was used at early and late stages of the disease. AZT-induced anemia was dose- and time-dependent. An increased percentage of erythroblasts in bone marrow was observed, with an increased ratio of early to late erythroblasts in both disease stages. Increases in splenic erythroid burst forming units (BFUe) were observed in early-stage AZT-treated mice. Mean plasma erythropoietin (EPO) levels were increased by AZT in both groups in a dose dependent manner and were inversely proportional to hematocrit values. These data suggest that the anemia induced by AZT stimulated a response by immature erythroid elements, but that the maturation or survival of early erythroblasts may be impaired. PMID- 1889488 TI - Acute leukemia in professional drivers exposed to gasoline and diesel. AB - The environmental exposure to the petroleum products gasoline, diesel, and their motor exhausts was studied in a case-control interview of 125 patients with acute leukemia and 1 matched control per patient. Odds ratios were calculated by comparing discordant matched patient-control pairs. An excess risk for developing acute leukemia was found for the professional drivers, and odds ratio was determined to be 3.0 (95% CI: 1.1-9.2/p less than or equal to 0.02). For those who were exposed for more than 5 years in their life-time, or more than 1 yr during the 5-20 yr period prior to diagnosis, the odds ratio was 5.0 (p less than 0.05). This finding remains after consideration is given to exposures to organic solvents, smoking and therapeutic x-ray treatment. No excess risk was observed for persons professionally exposed to motor oil and machine oil without exposure to fuels and exhausts. No preferential type of acute leukemia was found to be associated with exposure to fuels and their exhausts. The results indicate an etiological relationship between the development of acute leukemia and exposure to petroleum products as fuels and exhaust. PMID- 1889489 TI - Alveolar cell population in HIV infected patients. AB - Alveolar lymphocytosis, in the face of blood lymphopenia, is a common finding among patients with AIDS. We studied by bronchoalveolar lavage (BAL), the alveolar cell profile of 43 human immuno deficiency virus (HIV) seropositive patients divided into three groups involving the advanced stages of the disease: group A (n = 9; CDC III), ambulatory individuals without systemic or respiratory symptoms; group B (n = 15; CDC IV) patients admitted for evaluation of fever of unknown origin (FUO) without pulmonary involvement; group C (n = 19; CDC IV), patients admitted for evaluation of an acute pulmonary condition. Sex, age and risk factor were comparable among the groups. Alveolar lymphocytosis was found in no group A patients, in 2 out of 15 group B patients (both with P. carinii lung infection) and in all group C patients, where pulmonary involvement was due to opportunistic infection or to nonspecific interstitial pneumonitis. Our findings suggest that in patients with advanced HIV infection alveolar lymphocytosis may be an expression of a concomitant process within the lungs either clinically manifest or inapparent, or possibly related to HIV primary lung involvement. PMID- 1889490 TI - Ventilatory lung function in young cigarette smokers: a study of susceptibility. AB - The objective of this study was to estimate the effect of cigarette smoking on ventilatory lung function among young adults with special emphasis on the recognition of susceptible subgroups. In a cross-sectional study of 1,044 adults aged 15-40 yrs, a statistically significant linear relationship between quantity of smoking in cigarette-years and level of forced expiratory volume in one second (FEV1) was found. Among current cigarette smokers, FEV1 level was on average 35 ml lower for each 100 cigarette-years of exposure (corresponding to smoking of ten cigarettes per day for 10 yrs) compared to lifelong nonsmokers in a linear regression adjusted for confounding. Potentially susceptible subgroups were studied by introducing interaction terms between quantitative smoking and gender, wheezing, atopy, asthma, childhood respiratory illness and exposure to environmental tobacco smoke during the growth period, to the additive linear regression model explaining the FEV1 level. Wheezing was found to modify the effect of smoking significantly: the FEV1 level was on average 68 ml lower for each 100 cigarette-years due to interaction between smoking and wheezing. An introduction of the interaction term eliminated the independent effect of smoking. The results suggest that the detrimental effect of smoking on FEV1 in young adults may be limited to individuals with wheezing. Thus, the presence of wheezing among smokers indicates a higher risk for low level of ventilatory lung function compared to smokers who do not wheeze. PMID- 1889491 TI - Quantification of sleep disordered breathing by computerized analysis of oximetry, heart rate and snoring. AB - Intermittent snoring and cyclic oscillations of heart rate and oxyhaemoglobin saturation (Sao2) are characteristic features of the obstructive sleep apnoea syndrome (OSAS). Thus, overnight recordings of laryngeal sounds and heart rate by a portable device (MESAM) and of Sao2 by oximetry are applicable to screen outpatients for the presence of OSAS. Computerized analysis for time intervals of constant heart rate and intervals between snoring sounds is used by MESAM to quantify respiratory disturbances during sleep. Rapid increases in Sao2 during the postapnoeic hyperventilation period together with the number of desaturations are used by a new software for quantitative analysis of oximetry. To elucidate reliability of results from automatically scored MESAM and oximetry recordings, we compared the four computer calculated respiratory disturbance indices from heart rate (RDIH), snoring (RDIS), resaturations (RDIR) and desaturations (RDID) with the apnoea plus hypopnoea index (AHI) from simultaneously performed polysomnography. The study population consisted of 53 snorers with an AHI of 19.0 +/- 2.6 (median +/- SEM; range 0.7-87.8). Whereas both RDI's from MESAM correlated rather weakly with the AHI from polysomnography (RDIH: r = 0.32, p less than 0.05; RDIS: r = 0.33, p less than 0.05), this correlation was much better for the RDI's from oximetry (RDIR: r = 0.951, RDID: r = 0.93; p much less than 0.0001). Accepting a plus/minus 30 percent difference from the AHI, the RDIR classified 77% of patients correctly, the RDID 62%, the RDIS 32% and the RDIH 23%. In conclusion, results from computerized analysis of oximetry for desaturations and rapid resaturations correlate more closely with polysomnography than those from automatic scoring of MESAM recordings. PMID- 1889492 TI - Occurrence of breathing disorders during CPAP administration in obstructive sleep apnoea syndrome. AB - The spectrum of breathing events during sleep in patients with obstructive sleep apnoea syndrome (OSAS) after the abolition of obstructive apnoeas has been extensively studied in tracheostomized patients, but has received much less attention in patients submitted to continuous positive airway pressure (CPAP). We analysed the breathing pattern during sleep in forty patients while CPAP was administered. A regular breathing pattern throughout the sleep study was observed in 15 patients. In the remaining 25 subjects, one or more of the following events was observed: central apnoeas, hypopnoeas, periodic breathing, prolonged oxyhaemoglobin desaturations. Central apnoeas during non-rapid eye movement (NREM) sleep appeared almost exclusively after arousals or wakefulness periods; their prevalence did not significantly differ between subjects who showed and who did not show similar events before CPAP. Central apnoeas in rapid eye movement (REM) sleep had a random occurrence. Hypopnoeas were found only in REM sleep, and, like central apnoeas, occurred randomly; in one patient they had a prolonged duration (up to 110 s). Periodic breathing was observed in only two subjects, one of whom had congestive heart failure: it was limited to NREM sleep and was not associated with arousals or shifts in sleep stage. Prolonged oxyhaemoglobin desaturations were found mainly in REM sleep; most subjects with such abnormalities had daytime blood gas alterations. In conclusion, abnormalities of the breathing pattern of patients with OSAS can be observed during CPAP and after tracheostomy, but periodic breathing is less common than is reported after tracheostomy, and is probably caused by different mechanisms. PMID- 1889493 TI - The role of thromboxane in allergen-induced asthmatic responses. AB - In this study we evaluated the role of thromboxane in causing allergen-induced early and late asthmatic responses and airway hyperresponsiveness in asthmatic subjects. Twelve atopic subjects with stable asthma and documented early and late asthmatic responses to an inhaled allergen were treated with placebo or CGS 13080, a specific thromboxane synthetase inhibitor, given orally (200 mg four times daily) for two days before, the day of, and the day after allergen inhalation. Treatments were administered in a double-blind, placebo-controlled, crossover fashion. The effect of pretreatment with CGS 13080 was examined on serum TxB2 levels and the magnitude of the asthmatic responses after inhaled allergen. Serum TxB2 levels increased significantly from 96 ng.ml-1 (SEM 29) 3 h after diluent to 151 ng.ml-1 (SEM 27) 3 h after allergen (p = 0.008). CGS 13080 pretreatment markedly inhibited the levels of TxB2 at all time points before and after inhaled allergen (p = 0.0001) and had a small but significant effect on the magnitude of the early asthmatic responses after allergen (p = 0.0009). CGS 13080 did not alter either late asthmatic responses, baseline airway responsiveness, or the increase in histamine airway responsiveness after allergen. These results suggest that allergen-induced early asthmatic responses, but not late responses or allergen-induced airway hyperresponsiveness, are partly caused by thromboxane release. PMID- 1889494 TI - Comparison of the effects of intravenous almitrine and positive end-expiratory pressure on pulmonary gas exchange in adult respiratory distress syndrome. AB - The effects of almitrine on pulmonary gas exchange and haemodynamics were compared to those of positive end-expiratory pressure (PEEP) in 10 patients with a severe adult respiratory distress syndrome (ARDS) who required continuous mechanical ventilation. Haemodynamic and gas exchange measurements were made before and after 30 min of PEEP at a level of 10 cmH2O, then 30 min later, before and at the end of the intravenous infusion of almitrine at a dose of 0.25 mg.kg-1 in 30 min. There was no significant difference between baseline gas exchange and haemodynamic parameters. PEEP and almitrine increased Pao (p = 0.001) from 10.9 to 12.6 kPa and from 10.6 to 12.6 kPa (1 kPa = 7.5 mmHg), respectively, and ratio of venous admixture to total blood flow (Qs/Qt) decreased (p less than 0.001) from 34 to 29% and from 33 to 29%, respectively, the effects of PEEP and almitrine being not significantly different. Neither PEEP nor almitrine caused a significant change in arterial carbon dioxide tension (PaCO2). The haemodynamic parameters did not change significantly with almitrine, whereas mean systemic arterial pressure decreased from 85.4 to 81.1 mmHg (p less than 0.05) with PEEP. These results are consistent with the hypothesis that both treatments improve ventilation/perfusion (VA/Q) distributions, by an increase in functional residual capacity in the case of PEEP and a redistribution of pulmonary perfusion in the case of almitrine. PMID- 1889495 TI - Almitrine in low dose potentiates vasoconstrictor responses of isolated rat lungs to moderate hypoxia. AB - To test whether the effect of almitrine on hypoxic pulmonary vasoconstriction was dose-dependent, two series of experiments were performed on isolated rat lungs perfused with constant flow of blood. In the first series, the effects of different doses of almitrine on perfusion pressure were measured. Baseline perfusion pressure was not changed by solvent or by 0.25 micrograms.ml-1 almitrine, but it was increased by 0.5 and 2.0 micrograms.ml-1 almitrine. The increase in perfusion pressure in response to 10 min ventilation with hypoxic gas mixture (5% O2) was significantly (p less than 0.05) higher after 0.25 micrograms.ml-1 almitrine (12.0 +/- 0.8 torr) than before addition of the drug (5.43 +/- 1.8 torr). Responses to hypoxia were insignificant after higher doses (0.5 and 2.0 micrograms.ml-1) of almitrine. In the second series of experiments the responses to varying degrees of hypoxia were measured after administration of one dose of almitrine (0.25 micrograms.ml-1). Almitrine, compared to solvent alone, significantly altered the shape of the dose-response curve to hypoxia. Increases in perfusion pressure in response to moderate degrees of hypoxia were potentiated (10% O2: 8.7 +/- 1.8 torr after almitrine, 2.1 +/- 0.6 torr after solvent, p less than 0.05), whereas responses to severe hypoxia (3% O2) were not changed by almitrine. Reactivity to angiotensin II was decreased by 0.25 micrograms.ml-1 almitrine. We conclude that almitrine in low but not in high dose augments pulmonary vasoconstriction induced by mild degrees of hypoxia. PMID- 1889496 TI - Particle deposition and resistance in the noses of adults and children. AB - Nasal filter efficiency for particles has been described by several authors as showing large individual variations, probably somehow related to airflow resistance. Twelve children, aged 5.5-11.5 yrs and 8 aged 12-15 yrs were compared to a group of ten adults. Deposition of polystyrene beads (1, 2.05, 2.8 microns mass median aerodynamic diameter (MMAD] was measured by comparing inhaled aerosols and exhaled air concentrations, for both nose and mouth breathing. Ventilation was controlled to scale breathing patterns appropriate for each age either at rest or during moderate exercise to allow comparison between subjects in similar physiological conditions. Anterior nasal resistance (as a function of flow rate) and standard lung function were measured for each subject. For the same inhalation flow rate of 0.300 l.s-1, children had much higher nasal resistances than the adults, 0.425 +/- 0.208 kPa.l.1.s under 12 yrs, 0.243 +/- 0.080 kPa.l.1.s over 12 yrs and 0.145 +/- 0.047 kPa.l.1.s in adults. Individually, nasal deposition increased with particle size, ventilation flow rate and nasal resistance, from rest to exercise. The average nasal deposition percentages were lower in children than in adults, in similar conditions: at rest, 12.9 and 11.7 versus 15.6 for 1 microns; 13.3 and 15.9 versus 21.6 for 2.05 microns; 11 and 17.7 versus 20 for 2.8 microns. This was even more significant during exercise, 17.8 and 15.9 versus 29.2 for 1 microns; 21.3 and 18.4 versus 34.7 for 2.05 microns; 16 and 16.1 versus 36.8 for 2.8 microns.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1889497 TI - Active inspiratory impedance and neuromuscular respiratory output during halothane anaesthesia in humans. AB - The aim of this study was to measure, in 11 patients with healthy lungs, active inspiratory impedance during anaesthesia. In addition, we recorded changes in inspiratory occlusion pressure at 100 ms (P0.1) and ventilatory pattern while awake and during anaesthesia with a mean inspiratory fraction (FI) of 0.017 halothane in O2. The total active inspiratory resistance and elastance values were 5.4 +/- 3.3 hPa.l.1.s and 29.9 +/- 6.2 hPa.l.1, respectively. P0.1 and the ratio between P0.1 and mean inspiratory flow (P0.1/(VT/TI)) increased 124% (p less than 0.001) and 68% (p less than 0.001), respectively, during anaesthesia. Respiratory frequency rose significantly from 12.2 +/- 1.5 (mean +/- SD) to 24.6 +/- 4.6 cycles.min-1, while tidal volume and inspiratory duty cycle lowered significantly from 0.599 +/- 0.195 l and 0.44 +/- 0.04 to 0.372 +/- 0.088 l (p less than 0.001) and 0.40 +/- 0.04 (p less than 0.05), respectively. Minute ventilation (VE) and VT/TI did not change significantly. During halothane anaesthesia with an FI:0.017, the increase in neuromuscular respiratory output appears to compensate for the increased mechanical load, thus resulting in maintenance of VE at levels similar to those of an awake state. PMID- 1889498 TI - Ventilation-perfusion inequality in patients with non-alcoholic liver cirrhosis. AB - Ventilation-perfusion relationships were studied in patients with non-alcoholic liver cirrhosis. Spirometry was essentially normal but the transfer factor of the lung (DLCO) was reduced by an average 34% of predicted. Arterial oxygen tension (PaO2) ranged from normal down to 6.9 kPa. Varying degrees of ventilation perfusion (VA/Q) abnormalities (multiple inert gas elimination technique) were observed with increased dispersion of the perfusion distribution (log SDQ, 0.90; range 0.32-1.71; upper normal limit, 0.60) and the presence of both regions of low VA/Q ratios (between 0.1 and 0.005) (mean 4.1%; range 0-18.8%) and shunt (VA/Q ratios below 0.005) (mean 3.9%; range 0.19.8%). There was a close similarity between measured and calculated PaO2 in normoxaemic patients, but calculated values exceeded measured PaO2 in hypoxaemic patients. The difference between calculated and measured PaO2 correlated inversely to DLCO (r = 0.65, p less than 0.05). An inverse correlation was also noted between DLCO and the sum of shunt and low VA/Q regions (r = 0.87, p less than 0.001). It is concluded that hypoxaemia in non-alcoholic liver cirrhosis patients can be accounted for by intrapulmonary shunting and VA/Q mismatch, and possibly a "diffusion-perfusion" defect in patients with more severe gas exchange impairment. PMID- 1889499 TI - Sodium thiophene carboxylate does not facilitate expectoration. AB - A randomised double-blind crossover study compared the clinical effectiveness of a 21-day treatment with 600 mg per day of sodium thiophene carboxylate and placebo in 33 patients with stable chronic bronchial disease. During the seven week trial, subjective symptoms and findings were recorded, pulmonary function tests performed and sputum physical characteristics determined. Side-effects were closely monitored. Both subjective assessment of overall clinical efficacy and statistical analysis of the above mentioned factors failed to show any significant advantage of sodium thiophene carboxylate to placebo. Sodium thiophene carboxylate appears to be an expectorant and mucoregulatory drug, lacking evidence of clinical effectiveness in the treatment of patients with stable chronic bronchitis. PMID- 1889500 TI - Lack of effect of N-acetylcysteine on the release of oxygen radicals from neutrophils and alveolar macrophages. AB - N-acetylcysteine (NAC) is rapidly de-acetylated in vivo to cysteine (CYSH), a precursor of glutathione (GSH) which is an antioxidant in cells and body fluids. We investigated the effect of oral administration of N-acetyl cysteine for 5 days on the spontaneous and stimulated generation of hydrogen peroxide (H2O2) and superoxide anion (O2-) from human and rat phagocytic leucocytes. Alveolar macrophages (AM) were obtained by bronchoalveolar lavage (BAL) in control rats and rats given NAC in their drinking water. Neutrophils (PMNL) were harvested from whole blood in normal nonsmoking volunteers before and after NAC was given by mouth. The stimulated release of H2O2 and O2 from both rat AM and human PMN was not changed by administration of NAC. However, a small but significant increase was observed in both the spontaneous generation of O2- from rat AM and the spontaneous generation of H2O2 from human PMNL. Administration of NAC significantly increased cysteine levels in human plasma and rat BAL, but the levels in human PMNL and rat AM after NAC did not differ from control levels. GSH levels were not altered significantly by NAC. PMID- 1889501 TI - Neutral endopeptidase modulates neurogenic inflammation. AB - A noncholinergic, nonadrenergic nervous system has been described, involving the sensory nerves in the airways. Chemicals, dusts and other irritants stimulate these sensory nerves to release substance P and related neuropeptides. These neuropeptides have the remarkable ability to affect multiple cells in the airways and to provoke many responses including cough, mucus secretion, smooth muscle contraction, plasma extravasation and neutrophil adhesion. This series of effects is termed "neurogenic inflammation." An enzyme exists on the surfaces of all lung cells that contain receptors for these neuropeptides. This enzyme, neutral endopeptidase (NEP), by cleaving and thus inactivating the neuropeptides, limits the concentration of the neuropeptide that reaches the receptor on the cell surface. Thus, neurogenic inflammatory responses are normally mild and presumably protective in nature. However, when NEP is inhibited pharmacologically (with NEP inhibitors) or by cigarette smoke, respiratory viral infection, or by inhalation of the industrial pollutant toluene diisocyanate, neurogenic inflammatory responses are exaggerated. Delivery of exogenous human recombinant NEP inhibits neurogenic inflammation. Finally, evidence is provided that corticosteroids suppress neurogenic plasma extravasation and that this drug can upregulate NEP in human airway tissue. Neutral endopeptidase cleaves multiple peptides. Thus, its selectivity resides, at least in part, on its fixed location on the surfaces of specific cells where it can modulate effects of peptides exposed to the cells' surfaces. PMID- 1889502 TI - Evolution of a case of lung plasma cell granuloma. AB - Plasma cell granuloma, on lung inflammatory pseudotumour, is a localized benign proliferation of plasma cells and mesenchymal cells. We report the case of a 45 yr old male, who first presented with mild pain in the left side of the chest. Chest radiography was normal. Eight weeks later he had more pain and an opacity in the left and lower zones of his left chest. After another 7 weeks he had fever and cough with yellowish-green sputum. Chest X-ray then showed a round density in the left upper lobe. The final diagnosis was established after thoracotomy histological examination. PMID- 1889503 TI - Isolated intrathoracic tuberculous lymphadenopathy. AB - We report an 82 yr old man with isolated intrathoracic lymphadenopathy of tuberculous origin, which is an extremely uncommon presentation of tuberculosis especially in elderly Caucasian patients. The diagnosis was suggested by the computerized tomographic (CT)-scan showing central hypodense areas after contrast, and was subsequently proved by mediastinoscopic biopsy with histological and microbiological analysis. The atypical presentation of tuberculosis together with a negative two-step 5 international units of purified protein derivative (IU-PPD) tuberculin skin test and a frequent contact with a cavernous index case points towards a primary infection in this patient. PMID- 1889504 TI - Streptococcus group A pneumonia in an intravenous drug misuser (IVDM). AB - Streptococcus pyogenes appears to have become an uncommon cause of pneumonia. In view of the recent increase in S. pyogenes infections this situation is likely to change. An intravenous drug user presented with acute onset of fever and chills. At presentation pleuritic chest pain was a prominent symptom, and later he developed pulmonary abscesses and an empyema. The patient had a good response to benzyl penicillin, and his pulmonary lesions resolved completely. Although his clinical picture was characteristic of S. pyogenes pneumonia, it could easily be mistaken for Staphylococcus aureus septicaemia. PMID- 1889505 TI - Respiratory involvement in metal fume fever. PMID- 1889506 TI - NO and CO transfer. PMID- 1889507 TI - Which apparatus for inhaled pentamidine? A comparison of pulmonary deposition via eight nebulisers. PMID- 1889508 TI - [Occult papillary carcinoma of the thyroid presenting as a solitary pulmonary metastasis]. AB - This is a report of a quite rare case of occult papillary carcinoma of the thyroid in which the initial clinical manifestation was a solitary lung metastasis. A 58-year-old woman was referred to the Fukuoka University Hospital because a coin lesion approximately 5 cm in diameter was detected in the right lower lobe of the lung by routine roentgenographic examination. This abnormal finding by chest X-ray had been pointed out about fifteen years before. Although she did not remember the exact size of the lung tumor, it had grown minimally since that time. Otherwise, she had been in good health all her life. No abnormalities in clinical and laboratory tests were found on admission. The tumor was clinically suspected to be of benign nature (probably sclerosing hemangioma), and pulmonary lobectomy was performed. Microscopic examination of the tumor revealed a papillary carcinoma with focal areas of follicle formation and colloid production, consistent with metastatic thyroid carcinoma. Immunoperoxidase stain for thyroglobulin was strongly positive in the tumor, and this finding confirmed the thyroid origin. Repeated physical examination of the thyroid gland, thyroid scan, and thyroid function tests were all unremarkable, however, she was closely followed up for two years. Then, a thyroid nodule with cystic change was detected on the ultrasonogram. The patient underwent a right hemithyroidectomy, disclosing papillary adenocarcinoma histologically. This case suggests that thyroid cancer should be considered as possible primary site in cases of long-standing coin lesion on chest X-rays in patients without remarkable complaints and in whom the primary site is unknown. A search of the literature has revealed only five cases with occult thyroid carcinoma associated with solitary pulmonary metastasis. PMID- 1889509 TI - [The role of signal transduction systems in the regulation of the production and secretion of hCG (alpha, beta) by cultured human choriocarcinoma cells (BeWo)]. AB - The BeWo cell line, derived from choriocarcinoma, produces and releases human chorionic gonadotropin (hCG) and its alpha- and beta-subunits. The authors have already reported that cAMP and EGF stimulated the production and secretion of hCG and its subunits by cultured BeWo cells. Therefore, in order to elucidate the role of signal transduction systems (cAMP-A-kinase system, DG-C-kinase system and Ca(2+)-calmodulin system) in the regulation of hCG (alpha, beta) synthesis by human choriocarcinoma cells, effects of cholera toxin (CT), an activator of adenylate cyclase, phorbol 12-myristate 13-acetate (PMA), a protein kinase C activator, and Ca2+ ionophore A23187, an activator of Ca2+ modulation on hCG (alpha, beta) production and secretion by BeWo cells cultured in a serum-free condition were evaluated. Immunoreactive hCG alpha, hCG beta and hCG in the media and cultured cells were measured by each homologous RIA for hCG alpha, hCG beta and hCG, respectively. Addition of CT at a concentration of 100 ng/ml into the medium caused extreme increases in the cellular levels of hCG alpha, hCG beta and hCG together with remarkable increases in hCG alpha, hCG beta and hCG levels in the medium. This stimulatory effect of CT was first observed on the increase of hCG alpha levels in cultured BeWo cells and medium at 3h, then observed on the increase of hCG beta levels at 6h and was last detectable on the increase of hCG levels in the cultured cells and medium at 12h. Addition of PMA at a concentration of 100 ng/ml into the medium caused an increase in the cellular and medium levels of hCG alpha, hCG beta and hCG shortly (3h) after the exposure to PMA. Addition of A23187 at a concentration of 100 ng/ml into the medium caused a slight increase in hCG alpha levels in the medium at 6h without accompanying the increase in those cellular levels. When added together, PMA potentiated the stimulatory effect of CT on hCG alpha, hCG beta and hCG levels in the cultured BeWo cells and medium, while PMA did not potentiate the effect of A23187 in this experimental condition. These findings suggest that cAMP-A-kinase system plays a major role in the signal transduction of hCG (alpha, beta) synthesis and secretion by BeWo choriocarcinoma cells, and that DG-C-kinase system interacts synergistically with cAMP-A-kinase system in the regulation of hCG (alpha, beta) synthesis and secretion by BeWo cells. Ca(2+)-calmodulin system appears to participate in the regulation of hCG alpha secretion without affecting the synthesis of hCG (alpha, beta) in BeWo cells. PMID- 1889510 TI - [Renal sodium handling and renal dopaminergic activity in overweight normotensive subjects]. AB - Recently, we reported that the blunted natriuretic ability related to an attenuation of renal dopaminergic activity might play an important role in the hypertensive mechanisms of overweight patients with essential hypertension. On the other hand, the interrelationships between obesity, blood pressure and renal sodium handling in normotensives (NT) have not been clear. The purpose of the present study is to reveal the role of renal dopaminergic activity on renal sodium handling in overweight NT. The study consisted of 52 hospitalized NT receiving a regular diet containing 200mEq of sodium, 75mEq of potassium, 2400kcal/day, who were divided into two groups of 31 non-obese (NNT) and 21 obese (ONT) subjects. NNT was categorized as the body mass index (BMI) less than, and ONT as the BMI equal to or more than, 25kg/m2. In the early morning, after overnight fasting, all subjects remained in a supine state and were examined for renal clearance. During the clearance period, mean arterial pressure (MAP), heart rate (HR), endogenous creatinine clearance (Ccr), urinary excretion of sodium (UNaV), fractional excretion of sodium (FENa) and of inorganic phosphorus (FEP) and urinary excretion of free dopamine (uDA) were determined. There were no significant differences in age, HR, Ccr or UNaV between the two groups. Higher MAP and lower FENa) were observed in ONT than in NNT, but the differences in these parameters were not statistically significant. However, FENa in ONT was significantly lower than in MAP-and Ccr-matched NNT. In addition, FENa correlated negatively with BMI in ONT, unlike in NNT. MAP was correlated positively with FENa, and a similar tendency was found between MAP and FEP in NNT, but not in ONT. On the other hand, there was no significant correlation between BMI and uDA in either NNT or ONT. This result was different from our previous data in patients with essential hypertension (EHT) in which BMI correlated with uDA positively in non-obese EHT and negatively in obese EHT. These findings suggest that blunted natriuretic ability may exist in ONT, and the role of renal dopaminergic activity related to the attenuated natriuretic ability in ONT may be less important than in obese EHT. PMID- 1889511 TI - [19-Hydroxyandrostenedione in human ovarian vein measured by GC-MS]. AB - Nineteen-hydroxyandrostenedione (19-OHA) is considered to be an obligatory intermediate of estrogen synthesis. To clarify the role of 19-OHA in the human ovary, the following experiments were undertaken. Ovarian and peripheral vein blood in mid follicular and luteal phase were obtained from 14 women during gynecological surgery. The concentrations of androstenedione (A), testosterone (T), 19-OHA, estrone (E1) and estradiol (E2) were measured by gas chromatography mass spectrometry using deuterium-labeled steroids as internal standard. The effect of human chorionic gonadotropin (hCG) on those steroids was also studied in mid luteal phase. The concentrations of 19-OHA in ovarian vein were 1.20 +/- 0.16 ng/ml (mean +/- SE) in mid follicular and 0.78 +/- 0.18 ng/ml in mid luteal phase. The steroid levels measured in ovarian vein were significantly higher than those in peripheral vein. Though the administration of hCG in mid luteal phase enhanced A and E2 levels in ovarian vein, the levels of T, 19-OHA and E1 were not altered. Significant correlation between the levels of E2 and A was observed while none of the steroids correlated with 19-OHA. These results suggest, for the first time, that 19-OHA is produced and secreted from the human ovary. The question as to the physiological and biosynthetic role of ovarian 19-OHA has to be answered in the future. PMID- 1889512 TI - [Incidence of abnormal thyroid function in patients with low titers of thyroid microsomal antibodies]. AB - The incidence of abnormal thyroid function related to autoimmune disorders was examined in a district of Shimane Prefecture in 1988. Thyroid microsomal antibodies (MCPA) in sera were measured in a general population of 1,646, including 678 males and 968 females, aged 57.8 +/- 14.8 (mean +/- SD) yr. MCPA titer was defined as high (less than 1:128), low (1:16, 1:32, 1:64) or negative (less than 1:16) according to the highest dilution of test serum capable of agglutinating gelatin particles coated with the appropriate antigen. Test of MCPA revealed high titers in 141 subjects (group A), low in 43 subjects (group B) and negative in 1,462 (group C). Twenty-four patients with overt thyroid disorders were found in groups A and B: five with Graves' disease, two with Hashimoto's thyroiditis and 15 with goiter in group A, and two with goiter in group B. In the remaining 119 subjects in group A and 41 subjects in group B, serum free T4 (FT4) and TSH levels were measured. According to abnormalities in the levels of serum FT4 and/or TSH, their thyroid function was divided into the following 3 subgroups: 1) hyperthyroid (FT4 greater than 2.0 ng/dl, TSH less than 0.4 mu U/ml), 2) latent hypothyroid (0.8 less than FT4 less than 2.0 ng/dl, TSH greater than 5.0 mu U/ml) and 3) hypothyroid (FT4 less than 0.8 ng/dl, TSH greater than 5.0 mu U/ml). The hyperthyroid group consisted of two patients in group A and one in group B. Ten latent hypothyroid patients were found in group A and two in group B. Hypothyroidism was found in four patients in group A. The incidence of abnormal thyroid function was not different between group A (16 out of 119, 13.4%) and group B (three out of 41, 7.3%). Graves' disease and primary myxedema were found in one patient each in group B; these patients had no subjective symptoms but showed low titers of MCPA. These findings suggest that not only high titers of MCPA but also low titers of MCPA are closely related to abnormal thyroid function. PMID- 1889513 TI - [The frequency and mechanisms of urolithiasis in acromegaly]. AB - It is generally accepted that acromegaly is often associated with hypercalciuria, but there are few reports on the frequency and the mechanisms of urolithiasis. Recently we consecutively experienced 2 cases of acromegaly with urolithiasis, and these experiences made us investigate the association between urolithiasis and acromegaly. Among 18 acromegalies from 1977 to March 1990 (10 males, 8 females, 24-64 years old), 13 cases (72%) fulfilled the criteria of hypercalciuria (urinary calcium (u-Ca) greater than or equal to 200 mg/day or u Ca/urinary creatinine (u-Ca/u-Cr) greater than or equal to 0.15), and 7 cases (39%) suffered from urolithiasis that was diagnosed by KUB (4 cases) or X-ray computed tomography (CT) (3 cases). Especially in the last 2 years, 5 out of 7 cases (71%) were complicated with urolithiasis and all 7 cases were associated with hypercalciuria. These results suggest that hypercalciuria and urolithiasis are both much more frequent than previously reported. In 6 cases who were treated by pituitary adenomectomy from 1988-1989 (4 males, 2 females, 24-59 years old), we examined Ca metabolism before and after operation. Before operation, the levels of serum growth hormone (GH), u-Ca (mg/day), u-Ca/u-Cr (in all cases) and plasma somatomedin-C (Sm-C) (in 4 cases) were increased above the normal range. To determine the etiology of hypercalciuria, we performed the oral Ca load test under restriction of Ca (400 mg/day) and P (650 mg/day) intake. The results suggested that the hypercalciuria might be mainly due to the increased absorption of Ca from the intestine (so-called "Absorptive hypercalciuria"). However, the levels of serum vitamin D (Vit. D) metabolites were all within the normal range before operation. After operation, GH and u-Ca/u-Cr (in 5 cases) and u-Ca (mg/day) (in all cases) decreased significantly compared with before operation, and the levels of Sm-C (in all cases), serum 25-(OH)D3, 1 alpha, 25-(OH)2D3 (in 4 cases) and 24,25-(OH)2D3 (in 3 cases) were also reduced after operation. Surprisingly, u-Ca and u-Ca/u-Cr normalized only in 4 cases who showed a reduction in 1 alpha, 25-(OH)2D3 levels after operation, although there were no correlations between u-Ca (mg/day) or u-Ca/u-Cr and 1 alpha, 25-(OH)2D3. Significant correlations were found between u-Ca (mg/day) or u-Ca/u-Cr and Sm-C. The parathyroid function evaluated by the rapid Ca infusion test or nephrogenous cyclic adenosine monophosphate (NcAMP) was normal before and after operation.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1889514 TI - [Serum osteocalcin concentration in a patient with pseudohypoparathyroidism type Ib]. AB - A seventeen-year-old youth was presented with muscle cramps and convulsions. A brain CT scan showed calcification in the region of the ganglia, and a diagnosis of brain tumor was thus made and an anticonvulsant given for two years. At age nineteen, the patient developed pseudohypoparathyroidism owing to low serum calcium and high serum PTH levels. However, serum alkaline phosphatase and serum osteocalcin levels were high, lesion was detected in the femur neck. These data indicated that the bone remodeling response to PTH had remained intact in this patient. Serum osteocalcin is known to increase in primary hyperparathyroidism. However, unlike patients with hyperparathyroidism, those with pseudohypoparathyroidism show no increase in serum 1,25(OH)2D. The present case was thus useful for examining the direct effect of PTH on serum osteocalcin. The patient was administered 1 alpha (OH)D, and his condition monitored for two years. During this period, osteocalcin and PTH levels decreased while that of 1,25(OH)2D increased. Osteocalcin and PTH levels were found to be closely correlated (r = 0.68, p less than 0.01). The present results indicate the possibility that PTH may increase serum osteocalcin independent of Vitamin D. PMID- 1889515 TI - [The effect of growth hormone on leukopoiesis: in vivo and in vitro studies]. AB - Growth hormone (GH), which has been extracted from the pituitary gland since early times, has become easily available by the advance of genetic engineering in recent year. Its clinical application to treatment in various fields, involving obesity, wounds, fractures, gastric ulcers and so on, is being increasingly discussed. The presence or absence of the effect of GH on leukopoiesis was studied in vivo and in vitro experiments. In the in vivo experiment, GH was administered to rats whose bone marrow production had been suppressed by the injection of mitomycin C, and time-course changes in the peripheral blood leukocyte count in these rats were compared with those in rats given physiological saline solution alone (control group). The in vitro experiment was performed by colony assay of mouse marrow cells. Insulin growth factor-1 (IGF-1) was also studied in the in vitro experiment. The in vivo experiment revealed that GH promoted recovery of leukocytes from the nadir, and in the in vitro experiments GH and IGF-1 were demonstrated to increase the number of colonies in the presence of granulocyte macrophage colony stimulating factor (GM-CSF). GH was considered to exert effects on myeloid progenitor cells and the hemopoietic microenvironment simultaneously, resulting in an increase in leukocytes. PMID- 1889516 TI - Homologous desensitization of bombesin-stimulated Ins(1,4,5)P3 production in Swiss 3T3 fibroblasts. PMID- 1889517 TI - Effects of adipokinetic hormones on inositol phosphate metabolism in locust fat body. PMID- 1889518 TI - Epidermal growth factor stimulates phospholipase D activity in the absence of inositol lipid hydrolysis in Swiss 3T3 cells. PMID- 1889519 TI - Murine macrophage phospholipase A2. PMID- 1889520 TI - Late gestation changes in rat tissue phosphatidylcholine composition. PMID- 1889521 TI - The biosynthesis of phosphatidylcholine molecular species in fetal and neonatal guinea pig lung. PMID- 1889522 TI - The biosynthesis of molecular species of phosphatidylcholine in neonatal guinea pig liver. PMID- 1889523 TI - Differential activation of phospholipase A2 by protein kinase C in pituitary cells. PMID- 1889525 TI - Stimulation of DNA synthesis by 340nm/351nm UV laser irradiation. PMID- 1889524 TI - Differential regulation of gene expression in mouse parotid glands in response to isoprenaline treatment. PMID- 1889526 TI - Differential cisplatin responses in human carcinoma cell lines pre-exposed to fractionated X-irradiation. PMID- 1889527 TI - Properties of the diadenosine tetraphosphate nucleoside analogue, bis (N6 adenosyl)dodecane, and its possible use in the treatment of disorders of purine metabolism. PMID- 1889528 TI - Differential modulation of cisplatin cytotoxicity by human ovarian carcinoma cell lines in vitro. PMID- 1889529 TI - Trough levels of gentamicin do not indicate tissue accumulation. PMID- 1889530 TI - N-acetyltransferase in human urothelium and bladder cell lines. PMID- 1889531 TI - The effect of catecholamines on the metabolism of glutamine by skeletal muscle of the rat. PMID- 1889532 TI - The effect of an acute load of glucose on the rate of clearance of lactate from the blood of adult males after severe exercise. PMID- 1889533 TI - Dose related stimulation of glucose metabolism by peroxovanadate in rat skeletal muscle preparations in vitro. PMID- 1889534 TI - Effect of electrical stimulation of the sciatic nerve in anaesthetized rats on content of CGRP in rat skeletal muscle. PMID- 1889535 TI - Changes in serum lipids after exercise and on exposure to altitude. PMID- 1889536 TI - Metabolic changes in skeletal muscle of frog during exercise and recovery. PMID- 1889537 TI - The loading of fura 2 into mitochondria in intact rat heart and its use to estimate matrix Ca2+. PMID- 1889538 TI - Regulation of lipogenesis from lactate in isolated cells from early neonatal rat brain. PMID- 1889540 TI - Muscarinic acetylcholine receptors in the lung. PMID- 1889539 TI - The fate of lactate in isolated cells from early neonatal rat brain. Comparison with glucose and 3-hydroxybutyrate. PMID- 1889541 TI - The effect of perfusion rate on the apparent release of tritiated L-glutamate from superfused synaptosomes. PMID- 1889542 TI - Studies of presynaptic kainate and quisqualate effects on [Ca2+] i and phosphoinositide metabolism. PMID- 1889543 TI - Beta-endorphin C-terminal dipeptide elicits calcium influx and release of arachidonic acid metabolism in cortical neurones. PMID- 1889544 TI - Comparison of inositol 1,4,5-trisphosphate and inositol 1,3,4,5-tetrakisphosphate binding sites in cerebellum. PMID- 1889545 TI - Ethanolamine as well as choline is released to the external medium on phorbol ester and foetal calf serum stimulation of glial cells in primary culture. PMID- 1889546 TI - Observations on platelet prostaglandin metabolism in schizophrenia: the response to ADP. PMID- 1889547 TI - The effect of energy status on phosphatidylinositol turnover in rat brain. PMID- 1889548 TI - Investigation of the tissue distribution of the calcium independent kinase, Rx kinase; which is distinct from known isozymes of protein kinase C. PMID- 1889549 TI - Effect of Caprogen on membrane lipid peroxidation and motility of bovine sperm. PMID- 1889550 TI - Fourier transform infrared spectroscopy of (13C=O) trans-cinnamoyl- and (13C=O) hydrocinnamoyl-a-chymotrypsins. PMID- 1889551 TI - Light amplification by a coupled biological system: ATP, firefly luciferase and recycling of ATP. PMID- 1889552 TI - Predictions of cyclic GMP-dependent protein kinase structure from its primary sequence. PMID- 1889554 TI - Ethanol-induced reductions in skeletal muscle protein synthesis: use of the inhibitors of alcohol and aldehyde dehydrogenase. PMID- 1889553 TI - Effects of acute ethanol toxicity on protein synthesis in three anatomically distinct regions of the rat gut. PMID- 1889555 TI - Characterisation of microvascular endothelial cells derived from human fat. PMID- 1889556 TI - Gas liquid chromatography (GLC) analysis of hamster conjugated biliary bile acids. PMID- 1889557 TI - Active accumulation of creatine by cultured rat myoblasts. PMID- 1889558 TI - Collagen stimulation of intracellular calcium mobilization in washed platelets from patients with familial hypercholesterolaemia. PMID- 1889559 TI - One-step facile synthesis of radioactive acyl-CoA and acylcarnitines using rat liver outer mitochondrial membrane as the enzyme source. PMID- 1889560 TI - Immunoreactive [arginine] vasopressin (AVP) in human fetal and neonatal muscle. PMID- 1889561 TI - Net membrane permeability to Pi: a key factor controlling transient changes in cellular [Pi]. PMID- 1889562 TI - Prostaglandin metabolism in dystrophin-deficient MDX mouse muscle. PMID- 1889563 TI - DNA concentrations are increased in mdx mouse muscles. PMID- 1889564 TI - Immunoblotting of cerebellar proteins in multiple sclerosis. PMID- 1889565 TI - Enhanced lipid peroxidation in Duchenne dystrophy muscle may be secondary to muscle damage. PMID- 1889566 TI - Studies on the rat liver benzpyrene binding protein. PMID- 1889567 TI - Biosynthesis of platelet activating factor (PAF) by an osteosarcoma cell line (UMR 106). PMID- 1889568 TI - Selective increases in type II muscle protein synthesis in NSAID induced inflammatory bowel disease (IBD). PMID- 1889569 TI - Gut protein synthetic studies in a NSAID model of inflammatory bowel disease (IBD). PMID- 1889570 TI - Morphogenetic proteins from dentine extracellular matrix and cell-matrix interactions. PMID- 1889571 TI - Alterations in neuromuscular function following thermal injury. PMID- 1889572 TI - Yeast cells with a low-affinity binder of methotrexate. PMID- 1889573 TI - Dihydrofolate reductase from a reptile, uromastix. PMID- 1889574 TI - In situ hybridisation of a Y chromosome-specific probe to male myoblasts after implantation into female skeletal muscle. PMID- 1889576 TI - An investigation into the early effects of aortic constriction on the rates of protein synthesis in the rat heart. PMID- 1889577 TI - The effect of cell volume on the rate of lactate release from rat skeletal muscle. PMID- 1889575 TI - The effects of acutely administered anaesthesia on various plasma analytes, insulin and growth hormone concentrations and rates of cardiac and skeletal muscle protein synthesis in vivo in the rat. PMID- 1889578 TI - Genetic regulation of the pituitary control of smolting and sexual maturation in Atlantic salmon. PMID- 1889579 TI - Expression of chromosome 21 specific DNA sequences in brain tissue and in neuronal cell lines. PMID- 1889580 TI - Improved human faecal bile acid extraction. PMID- 1889581 TI - Inducible expression of mutant human proinsulins in a mouse pituitary cell line controlled by the mouse metallothionein promotor. PMID- 1889582 TI - The refolding of mitochondrial proteins after denaturation. PMID- 1889583 TI - Proton buffering in human skeletal muscle studied in vivo by phosphorus magnetic resonance spectroscopy. PMID- 1889584 TI - Age-dependent changes in cardiac muscle metabolism upon replacement of creatine by beta- guanidinopropionic acid. PMID- 1889585 TI - NMR visibility of ATP, PCr and Pi in the rat heart: effects of perfusion conditions. PMID- 1889586 TI - Energy status in the post myocardial infarcted rat heart. PMID- 1889587 TI - Prediction of serum apolipoprotein B levels from total cholesterol and triacylglycerols, or from total heparin-precipitable lipoprotein. PMID- 1889588 TI - N-acetyl-beta-D-glucosaminidase isoenzyme-A in human ovarian cyst adenoma. PMID- 1889589 TI - Effect of clenbuterol on the activity of proteolytic enzymes partially purified from rat skeletal muscle. PMID- 1889590 TI - Analysis of plasma lactate levels following ischemic exercise in patients with suspected metabolic myopathy. PMID- 1889592 TI - Separation of ferritin dimer, trimer and tetramer by preparative polyacrylamide gel electrophoresis and their identification by electron microscopy. PMID- 1889591 TI - A study of the distribution of desferrioxamine in the isolated perfused rabbit kidney. PMID- 1889593 TI - Lactate dehydrogenase isoenzymes from human heart: separation by preparative gel electrophoresis; and a crystalline preparation of isoenzyme--1. PMID- 1889594 TI - The generation of heavy atom derivatives by site-directed mutagenesis: can successful changes be rationalised? PMID- 1889595 TI - The influence of faecal exclusion on the colonic bile acid profile in Crohn's colitis. PMID- 1889596 TI - Chronological variation in faecal and ileal bile acid excretion. PMID- 1889597 TI - Serum phospholipase A2 and free fatty acid levels in acute pancreatitis. PMID- 1889598 TI - The influence of total colectomy on secondary bile acid metabolism. PMID- 1889599 TI - Human erythrocyte SOD in adults and normal, hypoxaemic, and anaemic foetuses. PMID- 1889600 TI - The biotin-carboxylation reaction of pyruvate carboxylase: the roles of acetyl CoA, Mg2+ and biotin. PMID- 1889601 TI - Human red cell malate dehydrogenase purification and antibody production. PMID- 1889602 TI - Reaction of N-terminal valine dipeptides with two ninhydrin derivatives. PMID- 1889603 TI - Demonstration of an isoenzymic form of a cell surface protease expressed in human colonic tumour cells but not in normal colonic cells. PMID- 1889604 TI - A scintillation proximity assay for transforming growth factor alpha (TGF alpha). PMID- 1889605 TI - Some glutathione-related enzymatic activities in skeletal muscle and myocardium of the rat. Adaptations to endurance training. PMID- 1889606 TI - N.m.r. and biochemistry. AB - The role and historical progress of n.m.r. applications in biochemistry are briefly outlined. Technical advances over the years have made n.m.r., at last, a technique which can give valuable information about a wide range of biochemical topics, from enzyme kinetics in vivo to the structure of protein-DNA complexes. Emphasis here is placed on studies of proteins, especially those made up from mosaics of modules. It is shown that n.m.r. can readily give detailed structural information about individual protein modules and that valuable information about the structure and function of the intact mosaic protein can be inferred. PMID- 1889607 TI - An overview of conventional and novel routes of protein secretion. AB - The purpose of this overview is to demonstrate the new complexities that have been revealed in secretory pathways. It is clear that in some areas (e.g. ATP driven translocators), mechanisms have been conserved between bacteria and higher eukaryotic cells, while certain new processes involve modified secretory routes (e.g. antigen presentation) which will be restricted to eukaryotic cells. It is generally believed that in the evolution of living systems, the development of membrane-delimited compartments was crucial, and that insertion of proteins into membranes allowed more control of the passage of molecules through the membrane. It has been suggested that the first secretory proteins were in fact membrane bound, and extracellular proteolysis was responsible for the release of the first soluble secretory proteins. If so, it is interesting to note that the process still exists today and Pandiella [259-262] has described how the release of the growth factor transforming growth factor-alpha (TGF alpha) from mammalian cells is a case of regulated surface proteolysis. Finally, it is clear to see that as regards secretory pathways, we should keep an open mind as to which routes are utilized and which are not, and indeed, which routes exist and which do not. It appears that if two secretory organelles exist then some protein will be shown to move between them. Even the cytosol can provide a reservoir for secretory proteins or peptides. Perhaps in time S. S. Rothman will be thought of as the Nostradamus of protein secretion. PMID- 1889608 TI - Interleukin 1 beta and thioredoxin are secreted through a novel pathway of secretion. PMID- 1889609 TI - Transforming growth factor-alpha. PMID- 1889610 TI - Transmembrane signalling by interleukin 2. PMID- 1889611 TI - Growth and differentiation in the haemopoietic system. PMID- 1889612 TI - Protein phosphorylation events and changes in inositol metabolism during HL60 cell differentiation. PMID- 1889613 TI - Regulation of the hydrolysis of phosphatidylcholine in Swiss 3T3 cells. PMID- 1889614 TI - Energy metabolism and fatigue during intense muscle contraction. PMID- 1889615 TI - Control of energetic processes in contracting human skeletal muscle. PMID- 1889616 TI - Effect of diet manipulation on substrate availability and metabolism in trained cyclists. PMID- 1889617 TI - Control of gene expression in adult skeletal muscle by changes in the inherent level of contractile activity. AB - The evidence presented here supports the concept that multiple, complex controls of gene regulation underlie the adaptive changes in protein quantity associated with alterations of the inherent amount of contractile activity in adult skeletal muscle. Investigations of increased contractile activity by running and resistance exercise, as well by recovery from the reduced contractile activity of limb immobilization suggest that control of the alterations of gene expression are initially (one day) at the level of translation. Likewise, experimental models which do not closely mimic human physical training (i.e. electrical stimulation and chronic overload) produce early alterations in the translational control of gene expression. More prolonged changes in contractile activity, brought about by either physical training or experimental models, produce altered gene expression via changes in pre-, post- and translational control. PMID- 1889618 TI - Retroviral vectors. PMID- 1889619 TI - Nerve-growth-factor-treated and v-src-expressing PC 12 cells: a model for neuronal differentiation. PMID- 1889620 TI - Arachidonic acid metabolism: potential for diverse signalling within the same neuron. PMID- 1889621 TI - Phorbol ester activation of the isotypes of protein kinase C from bovine and rat brain. PMID- 1889622 TI - Signal-dependent activation of phosphatidylcholine hydrolysis: role of phospholipase D. PMID- 1889623 TI - Arachidonate release consequent to bradykinin-stimulated phospholipid metabolism in dorsal root ganglion cells. PMID- 1889624 TI - Characterization of the nucleotide-modulated interaction of myth actin by n.m.r. spectroscopy. PMID- 1889625 TI - Fluorescence approaches to the study of the p21ras GTPase mechanism. AB - The use of ribose-modified guanine nucleotides and tryptophan mutants of p21ras, neither of which have significant effect on the kinetic mechanism of the p21ras GTPase and the GAP-activated p21ras GTPase, will now allow a detailed kinetic study of how GAP and other regulatory proteins interact with p21ras. This will lead to a better understanding of how the relative concentrations of 'active' p21ras. GTP and 'inactive' p21ras. GDP are regulated in the cell. PMID- 1889626 TI - Chirality and its importance in drug development: what are the issues? PMID- 1889627 TI - Chirality and its importance in drug development: a synthetic chemist's perspective. PMID- 1889628 TI - Chirality and its importance in drug development: an analytical chemist's perspective. PMID- 1889629 TI - Chiral drug metabolism: a perspective. PMID- 1889630 TI - A clinical pharmacologist's perspective. PMID- 1889631 TI - Regulatory implications: a committee member's perspective. PMID- 1889632 TI - Regulatory implications: an authority's perspective. PMID- 1889633 TI - Regulatory implications: a company's perspective. PMID- 1889634 TI - A patent lawyer's perspective. AB - The principles of patent law are first briefly explained. Particular patent problems which arise from the preparation of new drugs in novel chiral forms are then discussed and illustrated by reference to legal decisions. PMID- 1889635 TI - Chirality and its importance in drug development. PMID- 1889636 TI - Laser light scattering in biochemistry. Introductory remarks. PMID- 1889637 TI - Combined static and dynamic light scattering approaches to biopolymeric analysis. PMID- 1889638 TI - Low-bias macroscopic analysis of polydispersity. PMID- 1889639 TI - Mesoparticle diffusion in biopolymer and polymer solutions. PMID- 1889640 TI - An overview of current methods of analysing QLS data. PMID- 1889641 TI - Static and dynamic light scattering by semidilute rod-like polyelectrolyte solutions. PMID- 1889642 TI - A study of the diffusion of probe molecules in poly(N-isopropylacrylamide) gels using forced Rayleigh scattering. PMID- 1889643 TI - Developments in electrophoretic laser light scattering and some biochemical applications. PMID- 1889644 TI - Light scattering as a tool for characterizing biopolymer solutions and gels. PMID- 1889645 TI - Combined differential light scattering with various liquid chromatography separation techniques. PMID- 1889646 TI - Use of low-angle laser light scattering with gel permeation chromatography for the molecular mass determination of biomolecules. PMID- 1889647 TI - New tools for biochemists: combined laser Doppler micro-electrophoresis/photon correlation spectroscopy. PMID- 1889648 TI - An on-line dynamic light-scattering instrument for protein chromatography. PMID- 1889649 TI - Compactness of protein molecules in native and denatured states as revealed by laser light scattering and X-ray scattering. PMID- 1889650 TI - Dynamic light scattering from casein micelle suspensions. PMID- 1889651 TI - Light-scattering studies of protein association. PMID- 1889652 TI - Hydrodynamic behaviour of myosin filaments studied by laser light scattering. PMID- 1889653 TI - Quasi-elastic light-scattering studies of the assembly properties of microtubules. PMID- 1889654 TI - Quasi-elastic and total intensity light-scattering studies of mucin glycoproteins and cartilage proteoglycans. PMID- 1889655 TI - Use of on-line laser light-scattering photometry coupled to chromatographic separations for determination of biopolymer molecular mass, branching, size and shape distributions. PMID- 1889656 TI - Conformational aspects of ionic polysaccharides: laser light scattering of aqueous solutions of hyaluronic acid and alginate. PMID- 1889657 TI - Laser light-scattering studies of polysaccharide gels. PMID- 1889658 TI - Light scattering studies on DNA condensation. PMID- 1889659 TI - Dynamics and structures of DNA. PMID- 1889660 TI - Dynamics of oligonucleotides and DNA restriction fragments. PMID- 1889661 TI - Total intensity and quasi-elastic light-scattering applications in microbiology. PMID- 1889662 TI - Quasi-elastic light scattering studies of membrane structure and dynamics. PMID- 1889663 TI - Quasi-elastic light scattering from an evanescent wave to probe particle/wall interactions. PMID- 1889664 TI - Quasi-elastic laser light-scattering studies of size and dispersity of secretory vesicles and neurosecretosomes isolated from vertebrate neurohypophyses. PMID- 1889665 TI - Photon correlation spectroscopy and zeta potential characterization of model particles and colloidal drug carriers--essential information for the interpretation of cell culture studies. PMID- 1889667 TI - Particle sizing using methods of discrete Legendre analysis. PMID- 1889666 TI - Light scattering from liquid crystalline solutions of rod-like macromolecules. PMID- 1889668 TI - Size-exclusion chromatography/low-angle laser light scattering experiments to detect aggregation phenomena in biopolymer solutions. PMID- 1889669 TI - Bridging flocculation of polystyrene latex by beta-lactoglobulin: photon correlation spectroscopy studies. PMID- 1889670 TI - Gel permeation chromatography--multi-angle laser light scattering characterization of the molecular mass distribution of 'Pronova' sodium alginate. PMID- 1889671 TI - Photon correlation spectroscopy study of a 2311 bp relaxed circular DNA- applicability of Rouse-Zimm and wormlike chain models. PMID- 1889672 TI - Analysis of pH-induced population oscillations of Saccharomyces cerevisiae and Escherichia coli using photon correlation spectroscopy. AB - Following a recent successful application of p.c.s. to liquid chromatography in the biotechnology industry, its usefulness as a contamination monitor in the fermentation industry was assessed. It was found that: (i) the intensity bias of the technique limits its uses to the detection of contaminants when they are larger than the host; (ii) the inherent heterogeneity of microbial cultures prevents the use of multiangle studies, and (iii) the large size of bacteria make the use of p.c.s. in flowing, on-line systems impractical. PMID- 1889673 TI - Influence of scattering on physiological measurement using laser light in vivo. PMID- 1889674 TI - The interpretation of alignments between proteins of unusual sequence composition. PMID- 1889675 TI - Proteins of unusual sequence composition from the malarial parasite Plasmodium falciparum. PMID- 1889676 TI - Sulphur-poor prolamins of barley, wheat and rye. PMID- 1889677 TI - TonB; a model for signal transduction between membranes. PMID- 1889678 TI - Basic fibroblast growth factor in the developing bovine heart. PMID- 1889679 TI - Effects of age, vitamin D3 metabolites and calcium ionophore A23187 on cytosolic free calcium in rat hippocampus. PMID- 1889680 TI - The role of inositol transport in cellular differentiation. PMID- 1889681 TI - Effect of inhibitors of eicosanoid synthesis upon lymphocyte proliferation. PMID- 1889682 TI - Stimulation of U937 human monocytic cells by thrombin results in inositol trisphosphate formation and the mobilisation of intracellular Ca2+ but not the synthesis of thromboxane B2. PMID- 1889683 TI - Purification and characterisation of phospholipase A2 from human epidermis. PMID- 1889684 TI - The influence of inflammatory mediators on the effects of phenytoin on steroidogenesis by human gingival fibroblasts (HGF). PMID- 1889685 TI - Effects of phytoalexin elicitor on levels of inositol phosphates in lucerne cells in suspension culture. PMID- 1889686 TI - Kinetics of calcium mobilisation and inositol phosphate metabolism in endotoxin stimulated HL-60 cells. PMID- 1889687 TI - Natural resistance of W/Wv mice to ethanol-induced gastric lesions and its abrogation by bone marrow grafting: possible role of mast cells and LTC4. AB - The extent of ethanol-induced acute gastric lesions, gastric leukotriene C4 (LTC4) levels, and the number of gastric mucosal mast cells were examined in mast cell-deficient W/Wv mice, normal litter-mate +/+ mice, and bone marrow reconstituted W/Wv mice. After administration of ethanol, +/+ mice developed gastric lesions and elevation of gastric LTC4 levels in a dose dependent manner. In mast cell-deficient W/Wv mice, the extent of gastric lesions was far less than that of +/+ mice and the level of gastric LTC4 was not significantly altered. This difference was not due to anemia because blood-transfused non-anemic W/Wv mice were still resistant to ethanol-induced gastric lesions. When W/Wv mice were reconstituted with +/+ bone marrow cells, their natural resistance against ethanol-induced gastric lesions was abrogated. The extent of gastric lesions of bone marrow-reconstituted W/Wv mice paralleled with the increase in number of gastric mucosal mast cells and also with the level of gastric LTC4. Furthermore, ethanol-induced gastric lesions in bone marrow-reconstituted W/Wv mice was inhibited by pretreatment with 5-lipoxygenase inhibitor, AA-861, in a dose dependent manner. These results suggest that LTC4 may, even if it is not a prerequisite factor for ethanol induced acute gastric lesions, act as the amplitier in the sequential events of the pathogenesis. PMID- 1889688 TI - Colloidal bismuth subcitrate-induced changes on gastric mucosal hemodynamics in the rat: gastric mucosal blood flow after CBS treatment. AB - The belief that blood flow plays a central role in cytoprotection and there being no data available, at present, regarding the possible action of Colloidal bismuth subcitrate (CBS-DENOL) on the gastric mucosal blood flow (GMBF), led us to investigate its influence on mucosal hemodynamics in the rat stomach. Measurements of GMBF were performed in 32 male Wistar rats, treated by either CBS or placebo in drinking water for a 3-wk period, by the use of a laser-Doppler flowmeter, at 14 defined points of the stomach. CBS treated animals revealed a highly statistically significant increase (P less than 0.0005, upaired t-test) of GMBF in comparison with the placebo treated. These findings lead us to suggest that CBS exerts its antiulcer action via the mechanism of increased gastric mucosal blood flow. Additionally the increased blood flow may be associated with the previous findings of increased synthesis of prostaglandins, gastric mucus and bicarbonate secretion by CBS. PMID- 1889689 TI - Clinical course and long-term prognosis of Japanese patients with ulcerative colitis. AB - The course and prognosis of 308 patients with ulcerative colitis who visited Tohoku University Hospital during the period from 1954 to 1987 were investigated. Based these investigations, the following results were obtained. 1) In 27.6% of patients with proctitis, extension to the proximal colon developed during the observation period. 2) Surgical intervention was necessary in 33.9% of patients with total colitis and in 9.7% of those with left-sided colitis. 3) Of 1,566 patient-years in which the course was observed, 988 (63.1%) were active-years. When the course of ulcerative colitis was analyzed according to the duration and extent of involvement, the frequency of the attack-years in patients with proctitis or left-sided colitis steadily decreased with time. However, that of total colitis was constant, 65-85%, regardless of the follow-up period. Patients younger than age 20 at onset were prone to relapse during their course, compared with patients older than 20. 4) Ten patients died from causes related to ulcerative colitis in our hospital: 5 of them due to postoperative complications. Two patients developed colorectal cancer accompanying ulcerative colitis. 5) With respect to the cumulative survival rate, the 95% confidence limits of the observed curve was lower than the expected curve during the first 2 years and 12 16 years after the onset. The main causes of death were postoperative complications in the former and unrelated deaths of older patients in the latter. PMID- 1889690 TI - Mucosal lesions of the stomach in liver cirrhosis with a special reference to phospholipid metabolism. AB - Gastric mucosal lesions are an inevitable complication in patients with liver cirrhosis. Their etiology, however, is as yet unknown. The present study investigated phospholipid metabolism in the gastric mucosa of rats with cirrhosis induced by carbon tetrachloride. Gastric mucosal lesions were induced by taurocholic acid (TCA) which was given through a gastric tube. Levels of phospholipids, phosphatidylcholine, and disaturated-phosphatidylcholine were found to be markedly reduced at the mucosal surface in the cirrhotic rats, and they were increased in the gastric juice. Metabolism of phospholipids in the gastric mucosa was visualized by 3H-choline autoradiography and the rate of phospholipid metabolism was found to be reduced. These results strongly suggest that mucosal lesions induced by bile regurgitation into the stomach are due to disturbance of phospholipid metabolism in the gastric mucosa. PMID- 1889691 TI - Plasma free amino acid pattern in chronic hepatitis as a sensitive and prognostic index. AB - To evaluate the diagnostic and prognostic significance of plasma amino acid imbalance in chronic hepatitis (CH), plasma-free neutral amino acid levels were examined in 47 patients with CH, consisting of 8 chronic persistent hepatitis (CPH), 26 chronic aggressive hepatitis (CAH) 2A and 13 CAH 2B, compared with those of 58 patients with liver cirrhosis (LC) and of 12 healthy controls. Fischer's ratio (a molar ratio of branched chain amino acids to aromatic amino acids) was found to be reduced in the order of normal subjects (3.5 +/- 0.4), CPH (3.0 +/- 0.2), CAH2A (2.7 +/- 0.3), CAH2B (2.1 +/- 0.3), compensated LC (LC-C, 1.5 +/- 0.4) and decompensated LC (LC-D, 1.1 +/- 0.2). Patients with CPH showed a significant decrease of the ratio compared with normal subjects (P less than 0.05). The ratio was significantly higher in patients with CAH 2B in comparison with LC-C (P less than 0.001). Especially, the ratio could be used to discriminate the three distinct stages of CH. Discriminant analysis, carried out using six amino acids, Fischer's ratio and conventional liver function tests indicated that Fischer's ratio was the most reliable parameter for differentiation of the three stages of CH. Furthermore, serial examinations of Fischer's ratio in patients with CH remained unchanged in CPH, whereas was significantly reduced in CAH during 2-3 years follow-up. These results strongly suggest that Fischer's ratio is a useful indicator for differential diagnosis and for prediction of the subsequent clinical course of CH as well as being a sensitive index for functional hepatic reserve in chronic active liver diseases. PMID- 1889692 TI - Uptake of bilirubin glucuronides by isolated rat hepatocytes. AB - The uptake of bilirubin diglucuronide (BDG) into isolated rat hepatocytes was investigated in order to characterize the mechanism by which bile pigments are transported by the liver. The BDG uptake by hepatocytes was saturable. The uptake was inhibited by bilirubin, sulfobromophthalein, and bilirubin monoglucuronide, but not by taurocholate. The uptake was not affected by replacement of sodium with other cations except for choline. Only when sodium was replaced with choline, was significant decrease in uptake observed. When chloride was replaced with nitrate, BDG uptake decreased, but it was not changed by replacement with sulfate. Metabolic inhibitors did not affect BDG uptake significantly. Thus bile pigments share a common sodium-independent and electrogenic potential-dependent transporter in liver cell membranes. A high concentration of albumin interferes with BDG uptake. PMID- 1889693 TI - A case of prominent hepatic cholestasis developing to hepatic failure in lambda AL amyloidosis. AB - We report a case of lambda-AL amyloidosis which manifested prominent hepatic cholestasis. The patient was a 71-year-old Japanese male who was admitted to our hospital because of abdominal distension and jaundice. Laboratory examination revealed a marked deterioration of liver function with cholestasis. Gastric biopsy revealed amyloid deposition. Under a diagnosis of primary amyloidosis he was treated with corticosteroid and dimethylsulfoxide. However, jaundice progressed, renal function deteriorated rapidly, and he died two weeks after admission. Autopsy revealed a profound deposition of lambda-AL amyloid not only in the liver but also in the kidneys, spleen, lungs, heart and intestine. PMID- 1889694 TI - Electroencephalogram patterns during sleep reflux in infants. AB - Twenty-four infants, 3-35 months of age, with histories of apnea or chronic lung disease underwent nighttime polysomnography and esophageal pH monitoring. Fifteen infants had pathological levels of gastroesophageal reflux on esophageal pH monitoring, and 9 had normal study results (symptomatic controls). Partition of sleep stages, sleep efficiency, and frequency of arousals to electroencephalographic stage 0 were the same in both groups. During sleeping reflux episodes, defined as reflux starting during sleep stages 1-5 or reflux episodes consisting of greater than 50% of sleep stages 1-5, there was a 50% decrease in the amount of stage 0 electroencephalogram pattern compared with nonreflux sleep, and a compensatory increase in the non-rapid eye movement sleep stages. Reflux onsets in patients with pathological reflux were evenly divided between stages 0, 1/2, and 5. Onset of reflux occurred rarely during sleep stages 3 and 4. Slight body movement accompanied the onset of 62.5% of sleep reflux episodes in symptomatic controls and 64.7% in patients with pathological gastroesophageal reflux. Arousals to stage 0 electroencephalogram occurred with equal frequency in sleep reflux episodes of symptomatic controls and patients, and frequency did not increase over the observed value for nonreflux time. There were no differences between the sleep patterns of infants with and without pathological gastroesophageal reflux; nor were there decreases in arousals from sleep in infants with pathological reflux. However, reflux occurring during sleep in all infants studied was characterized by a significant decrease in stage 0 (waking) electroencephalogram. PMID- 1889695 TI - Increased activation of isolated intestinal lamina propria mononuclear cells in inflammatory bowel disease. AB - Normal human lamina propria lymphocytes are in a heightened state of activation compared with peripheral blood with regard to cell-surface activation antigen expression (transferrin receptor, interleukin-2 receptor, 4F2) and the increased spontaneous secretion of immunoglobulins in vitro. This study evaluates the cell surface expression of activation-associated antigens in different subpopulations of isolated colonic lamina propria mononuclear cells in inflammatory bowel disease. In pilot studies using three-color flow cytometry, autofluorescence was observed that was emitted by unstained lamina propria mononuclear cells, which interfered with both the sensitivity and the specificity of the analyses. Because a major portion of the intestinal lymphocyte populations of interest were autofluorescent, a method to remove autofluorescence signals was developed by designing a computer program for the subtraction of autofluorescence from the emissions of each individual cell. This technique increases both the sensitivity and specificity of flow-cytometric analyses of intestinal lamina propria mononuclear cells. Using fluorescence-activated cell-sorter analyses with subtraction of autofluorescence on a single-cell basis, increased expression of lymphocyte activation antigens (interleukin-2 receptor, transferrin receptor, 4F2) was found on the cell surface of isolated intestinal B cells, T cells, CD4+ T cells, and CD8+ T cells in both Crohn's disease and ulcerative colitis. Therefore, markedly increased intestinal lymphocyte activation is a major immunological alteration in inflammatory bowel disease and includes all lymphocyte subpopulations investigated in this study. In addition, 5 aminosalicylic acid, which is used for the treatment of intestinal inflammation in inflammatory bowel disease, inhibits the expression of cell-surface activation antigens on mitogen-activated peripheral blood lymphocytes in a dose-dependent manner. These observations suggest that lymphocyte activation may play an important role in underlying immune processes that lead to chronicity and perpetuation of inflammatory bowel disease and may implicate an additional mechanism for the therapeutic action of 5-aminosalicylic acid. PMID- 1889697 TI - Reversal of protein-bound vitamin B12 malabsorption with antibiotics in atrophic gastritis. AB - The role of bacteria in the bioavailability of protein-bound vitamin B12 was examined in eight elderly subjects who had atrophic gastritis and in eight normal controls. On separate days and in random order, vitamin B12 absorption tests were performed using either radiolabeled crystalline or protein-bound vitamin B12. At the same time, bacterial samples were collected from the upper gastrointestinal tract. The tests and gastrointestinal aspirates were performed before and during tetracycline therapy. Crystalline vitamin B12 was absorbed to the same extent in the two study groups. Atrophic gastritis subjects absorbed significantly less protein-bound vitamin B12 than normal controls (mean +/- SEM, 0.7% +/- 0.2% vs. 1.9% +/- 0.5%, respectively). However, protein-bound vitamin B12 absorption in these subjects normalized after antibiotic therapy. These results suggest that the small amounts of vitamin B12 released from the protein binders is readily absorbed (as shown in vitro) and/or metabolized by bacteria. PMID- 1889696 TI - Effects of diazepam and Ro 15-1788 on duodenal bicarbonate secretion in the rat. AB - Bicarbonate secretion by duodenal mucosa just distal to the Brunner's glands area and devoid of pancreatic secretions was titrated in situ in anesthetized rats. Intravenous injection of diazepam (0.1 and 0.5 mg/kg) significantly increased the secretion; this stimulation was abolished by proximal bilateral vagotomy. Ro 15 1788, a benzodiazepine antagonist that also has well-known intrinsic activity, caused similar stimulation of the secretion when administered IV (0.01 and 0.1 mg/kg). Intracerebroventricular infusion of Ro 15-1788 (10 micrograms/h) resulted in a greater increase in secretion; again, this stimulation was prevented by vagotomy. Adrenoceptor blockade by phentolamine increased basal alkaline secretion but did not affect the stimulation by diazepam. The tricyclic antidepressant trimipramine (2.5 mg/kg IV) did not affect the duodenal bicarbonate secretion. For comparison, effects of diazepam and Ro 15-1788 (10(-6) 10(-4) mol/L) were also tested in isolated bullfrog duodenal mucosa. Neither drug effected the alkaline secretion in vitro. The combined results strongly suggest that benzodiazepines, as previously shown for certain brain peptides, influence the central nervous control of duodenal mucosal alkaline secretion and that their stimulation of secretion is vagally mediated. This action benzodiazepines might be used in modulating mucosal protection against acid. PMID- 1889698 TI - Light and electron microscopy of neuropeptide Y-containing nerves in human liver, gallbladder, and pancreas. AB - Neuropeptide Y-containing nerve fibers were identified by light and electron microscopic immunocytochemistry in the human liver, gallbladder, and pancreas. In the liver, neuropeptide Y-containing nerve fibers were distributed richly in Glisson's sheath and were prominent around the walls of the interlobular vein, interlobular hepatic artery, and hepatic bile duct. The fibers also formed a dense network surrounding the hepatocytes. The nerve terminals were found close to the endothelial cells of blood vessels, as well as being distributed in Disse's space, where they appeared to terminate. Occasionally these terminals contacted directly the membrane of a hepatocyte. In the gallbladder, neuropeptide Y fibers were found in each layer, with an especially dense network in the lamina propria. The fibers also ran close to the epithelium and parallel to the muscle bundles. Blood vessels throughout the gallbladder were well supplied with such nerve fibers. In the pancreas, neuropeptide Y fibers were found mainly near blood vessels and partly in gaps between exocrine glands, seeming to terminate on certain endocrine cells. Nerve terminals were located in the vascular walls and adjacent to the surface of exocrine acinar cells. These studies provide a basis for correlating the neuropeptide Y distribution with pharmacological and physiological studies in humans. PMID- 1889699 TI - Complications of endoscopic sphincterotomy. A prospective series with emphasis on the increased risk associated with sphincter of Oddi dysfunction and nondilated bile ducts. AB - Mostly retrospective series with limited use of sphincter of Oddi manometry have indicated that early complications are more common when endoscopic sphincterotomy is performed for sphincter of Oddi dysfunction than for common duct stones. The current study was undertaken to prospectively evaluate the frequency and type of complications of endoscopic sphincterotomy performed for sphincter of Oddi dysfunction compared with endoscopic sphincterotomy performed for other conditions. Four hundred twenty-three patients underwent sphincterotomy for sphincter of Oddi dysfunction (166), common duct stone(s) (163), tumor (60), and miscellaneous reasons (34). Patients were observed in the hospital for at least 24 hours after the procedure, and 30-day follow-up data were obtained. The overall complication rate was 6.9%, but complications were more frequent when sphincterotomy was performed for sphincter of Oddi dysfunction than for all other indications (10.8% vs. 4.3%; P = 0.009). Precut sphincterotomy was more frequently required in the sphincter of Oddi dysfunction group (21.1% vs. 11.7%, P = 0.009) but was no more likely to result in a complication (6.2%) than standard sphincterotomy. The risk of a complication was considerable for a small diameter common bile duct (less than or equal to 5 mm), particularly when sphincterotomy was performed for sphincter of Oddi dysfunction (37.5%). The overall 30-day mortality rate was 1.7%, but the procedure-related mortality rate was believed to be 0.2%. It is concluded that endoscopic sphincterotomy for sphincter of Oddi dysfunction is more hazardous than for other conditions, particularly when a small common bile duct is present. PMID- 1889700 TI - Defective Fc receptor-mediated clearance in patients with primary biliary cirrhosis. AB - Fc receptor-mediated clearance of immunoglobulin G-coated autologous erythrocytes was studied in patients with primary biliary cirrhosis (n = 14), alcoholic liver cirrhosis (n = 5) and healthy reference individuals (n = 14). The mean half-life of the sensitized erythrocytes was significantly prolonged in patients with primary biliary cirrhosis (85 +/- 25 minutes; P less than 0.001) compared with the corresponding value in patients with alcoholic cirrhosis (16 +/- 2 minutes) and healthy reference individuals (20 +/- 5 minutes), respectively. No correlation between clearance rate and age, liver histopathology, or serum levels of bilirubin, aminotransferases, immunoglobulin G, immunoglobulin A, and Clq binding or C3-containing immune complexes was found. The results presented here indicate a profound disturbance of Fc receptor-mediated immune clearance function in patients with primary biliary cirrhosis. PMID- 1889701 TI - Azathioprine treatment increases hepatocyte turnover. AB - The effect of azathioprine on the hepatocytes cell turnover was evaluated. This was accomplished by injection of rats with trituim thymidine. The distance of labeled liver cells from the portal space was determined, after 1 hour and 30 days, in control and azathioprine-treated rats. In the control group, the streaming velocities of hepatocytes and littoral cells were 3.2 microns/day and 3.1 microns/day, respectively. In azathioprine-treated animals, the respective velocities were 7.0 microns/day and 5.5 microns/day. In the liver acinus, cell displacement velocity is proportional to cell production. Because hepatocyte velocity in azathioprine-treated animals increased by 218% and littoral cell velocity by 177%, their respective turnovers also increased to 218% and 177%. It can be concluded that the liver is essentially a slowly renewing cell population. Azathioprine increased the hepatocytes' and littoral cells' streaming velocities. This in vivo experimental model may help evaluate the effect of hepatotoxic drugs on the kinetics of liver cells. PMID- 1889702 TI - Prophylactic sclerotherapy in high-risk cirrhotics selected by endoscopic criteria. A multicenter randomized controlled trial. AB - Controlled trials of sclerotherapy for the prevention of the first variceal hemorrhage in cirrhotics have given conflicting results. In the present study, 106 cirrhotics were randomized to sclerotherapy (55 patients) or control group (51 patients). Admission criteria were no history of previous variceal bleeding and the presence of high-risk varices, i.e., a variceal score less than or equal to 0 according to Beppu et al. Sclerotherapy sessions were performed at time zero, 7 days, 30 days, and then monthly until eradication. Follow-up endoscopies were performed at 6-month intervals thereafter. Control patients underwent repeat endoscopy at 6-month intervals. Bleeding episodes were treated by sclerotherapy in both groups, whenever possible. Mean follow-up was 24 months. Analysis of the results was performed by the intention-to-treat method. Variceal bleeding occurred in 19 sclerotherapy patients (34.5%) and in 17 controls (35.4%, P = NS). Overall mortality was 34.5% in sclerotherapy patients and 50% in controls (P = NS). Seven of the 19 sclerotherapy patients (36.8%) and 11 of the 17 controls (64.7%) who bled died of hemorrhage (P less than 0.05, log-linear model). It is concluded that prophylactic sclerotherapy does not reduce the incidence of first variceal bleeding in cirrhotics. However, there seems to be a trend toward a lower bleeding-related mortality in sclerotherapy patients than in controls. PMID- 1889703 TI - An Na(+)-dependent and an Na(+)-independent system for glutamine transport in rat liver basolateral membrane vesicles. AB - In the present study the transport of glutamine across rat liver basolateral membrane was examined with special emphasis on the existence of an Na(+) independent system and on the characteristics of the Na(+)-dependent system with respect to stoichiometry of glutamine to Na+. Well-validated and purified liver basolateral membrane vesicles were used in the study. Results of studies on the effect of incubation medium osmolarity and incubation temperature indicated that glutamine uptake by liver basolateral membrane vesicles is largely the result of transport of the substrate into the intravesicular compartment with little binding to basolateral membrane vesicles. Transport of glutamine with time was Na+ gradient dependent (out greater than in) with a distinct "overshoot" phenomenon. Replacing Na+ with an equivalent concentration of K+, NH4+, choline, or mannitol caused significant inhibition of the initial rate of glutamine transport; on the other hand, Li+ could partially substitute for Na+. The initial rate of transport of glutamine as a function of concentration (0.05-12 mmol/L) was saturable both in the presence and in the absence of an inwardly directed Na+ gradient. Apparent Km values of 2.95 and 3.35 mmol/L and Vmax values of 11,565 and 6663 pmol.mg protein-1.10s-1 were calculated in the presence and absence of a Na+ gradient, respectively. Both in the presence and absence of an Na+ gradient (out greater than in), transport of [3H]glutamine was significantly inhibited by the addition to the incubation medium of unlabeled glutamine as well as histidine, asparagine, and serine. Transport of glutamine by the Na(+)-dependent process was significantly inhibited or stimulated, respectively, by inducing a relatively positive or negative intravesicular space. On the other hand, glutamine transport by the Na(+)-independent process was not affected by changes in transmembrane electrical potential. Using the "activation method," the stoichiometry of glutamine Na+ transport was found to be 1:1. These results show that glutamine transport in rat liver basolateral membrane vesicles is carrier mediated both in the presence and absence of an Na+ gradient. Furthermore, the Na(+)-dependent process is electrogenic in nature (net positive) and cotransports one glutamine molecule with one Na+. Transport of glutamine by the Na(+) independent system, on the other hand, is electroneutral in nature. PMID- 1889704 TI - Glucocorticoids stimulate ornithine decarboxylase gene expression in pancreatic AR42J cells. AB - The effects of dexamethasone on ornithine decarboxylase gene expression were examined in rat pancreatic AR42J cells. Dexamethasone increased ornithine decarboxylase activity and messenger RNA (mRNA) concentrations in a time dependent manner, with a maximal effect at 12 hours (207% +/- 63% and 327% +/- 34% of control, respectively; n = 5). Ornithine decarboxylase mRNA levels returned to control values at 48 hours, whereas ornithine decarboxylase activity was decreased to 41% +/- 8% of control (n = 3). Dexamethasone induction of ornithine decarboxylase mRNA was dose dependent, with half-maximal effects at 10( 8) mol/L (210% +/- 20% of control; n = 4) and maximal effects at 10(-7) mol/L (327% +/- 26% of control; n = 4). The glucocorticoid antagonist RU 38486 blocked the dexamethasone effects in a dose-dependent manner, with maximal effects occurring at 10(-7) mol/L (120% +/- 18% of control; n = 3). When protein synthesis was blocked by addition of cycloheximide, ornithine decarboxylase mRNA levels remained unchanged in response to glucocorticoids, indicating a primary effect of dexamethasone. Furthermore, cycloheximide by itself had no significant effect on ornithine decarboxylase mRNA levels. Inhibition of transcription with actinomycin D showed a half-life for ornithine decarboxylase mRNA of approximately 240 minutes. Ornithine decarboxylase mRNA stability was not affected by dexamethasone pretreatment for 12 hours. Therefore, these data suggest that dexamethasone regulates ODC gene expression via glucocorticoid receptor-mediated gene transcription. Furthermore, translational mechanisms seem to be involved in glucocorticoid-regulated ornithine decarboxylase induction. PMID- 1889705 TI - Fecal incontinence in a 39-year-old man. PMID- 1889706 TI - Treatment of severe postgastrectomy dumping with a long-acting somatostatin analog: is effective management finally available? PMID- 1889707 TI - Recurrent hepatitis B in liver transplant recipients--no easy answers. PMID- 1889708 TI - Concentration in pancreatic juice of lithostathine. PMID- 1889709 TI - Pathogenesis and treatment of rotavirus diarrhea. PMID- 1889710 TI - Prevalence of spontaneous hepatofugal portal flow in liver cirrhosis. PMID- 1889711 TI - Hyperplastic polyps and risk of adenomas. PMID- 1889712 TI - The effect of histamine H2-receptor blockade on bismuth absorption from three ulcer-healing compounds. AB - Twelve healthy male subjects were dosed with six regimens: ranitidine and De Noltab (tripotassium dicitrato bismuthate; Gist-Brocades Ltd., Weybridge, England), placebo and De-Noltab, ranitidine and Pepto-Bismol liquid [bismuth salicylate; Procter & Gamble (Health and Beauty Care) Ltd., Egham, England], placebo and Pepto-Bismol, ranitidine and Roter tablets (bismuth subnitrate; Roter Pharma Ltd., Ashford, England), and placebo and Roter. Ranitidine, 300 mg, or placebo was administered at 10 PM (night before) and at 7 AM; at 9 AM, the oral dose of bismuth was either 2 De-Noltabs, 3 30-mL doses of Pepto-Bismol liquid, or 2 Roter tablets. When predosed with placebo, the median integrated 8-hour plasma bismuth concentration was significantly greater after dosing with De-Noltabs than after dosing with either Pepto-Bismol or Roter (61, 8, and 8 ng.h/mL, respectively), with a similar trend for 8-hour median urinary bismuth excretion (213, 40, and 6 micrograms, respectively). When predosed with ranitidine, only after De-Noltab administration were there significant increases in the 8-hour plasma bismuth concentration (147 ng.h/mL), and 8-hour urinary bismuth excretion (686 micrograms). Eliminating intragastric acidity may enhance bismuth absorption after oral dosing with De-Noltabs by maintaining intragastric tripotassium dicitrato bismuthate as a colloidal suspension. PMID- 1889713 TI - Electrolyte transport in piglets infected with transmissible gastroenteritis virus. Stimulation by verapamil and clonidine. AB - The effects of clonidine, an alpha 2-adrenergic agonist, and verapamil, a Ca2+ channel blocker, on Na+ and Cl- absorption were studied in stripped jejunal mucosa from control and transmissible-gastroenteritis-virus-infected piglets. All infected piglets developed severe diarrhea 18-24 hours after oral inoculation. Jejunum from infected animals, as compared with control jejunum, had decreased mucosal-to-serosal, serosal-to-mucosal, and net Na+ and Cl- fluxes. Clonidine and verapamil caused a decrease in short-circuit current and stimulation of Na+ and Cl- absorption in control jejunum. In infected piglets, although the jejunum exhibited severe villus atrophy, both drugs stimulated Na+ and Cl- absorption and the magnitude of Na+ and Cl- absorption was similar in control and transmissible gastroenteritis-infected jejunum. In contrast, D-glucose stimulated Na+ absorption, and the decrease in short-circuit current caused by verapamil and clonidine, were decreased in transmissible-gastroenteritis-infected jejunum. Such pharmacological stimulation of Na+ and Cl- absorption might be useful in the management and treatment of certain viral diarrheal diseases. PMID- 1889714 TI - Comparative evaluation of acid- and bile-induced damage to pedicled jejunal or colonic segments in the rat. AB - The choice of the esophageal substitute after surgical resection for peptic stricture lies between the colon and jejunum. The current study was designed to compare long-term resistance of the colonic and jejunal mucosa to gastric or mixed duodenogastric secretions. The following preparations were performed in Wistar rats: transposition of a colonic or jejunal patch (a) to the gastric body, with or without truncal vagotomy, or (b) to the gastric antrum and proximal duodenum, with or without truncal vagotomy. Jejunal and colonic patches were removed 4, 8, and 12 months after surgery. The only damage to the transposed mucosae was the alteration of microvilli. The alteration was more severe in colonic than in jejunal patches and was prevented by truncal vagotomy. Long-term resistance of the transposed mucosae to the environmental challenge may depend on their adaptation potentiality, involving both specific and nonspecific mechanisms. Nonspecific mechanisms include the increased production of mucus and the gastric-like transformation of the superficial epithelial layer. Specific mechanisms include the reduction of the mucosal surface size for jejunal segments and the shifting in mucin secretion patterns for colonic segments. PMID- 1889715 TI - Comparative evaluation of carcinoembryonic antigen, secretory component, and mucins in index and metachronous adenomas of the colorectum. AB - Of 124 patients who underwent endoscopic polypectomy, 70 were colonoscopically reevaluated during a mean period of 10 years. On the basis of the clinical outcome, the patients were divided into three groups: group 1, 31 patients who had a colon still with no adenomas or cancer; group 2, 35 patients in whom one or more metachronous adenomatous polyps developed; and group 3, 4 patients in whom a carcinoma of the colon subsequently developed. In addition to the clinical and pathological features, the pattern of the immunohistologic staining for carcinoembryonic antigen and secretory component was studied. Moreover, the mucin histochemical staining intensity of neutral mucins, sulfomucins, and sialomucins was evaluated. The features of the 40 index adenomas obtained from patients in group 1 were compared with the features of the 51 index adenomas from patients in group 2. Furthermore, these characteristics of the index adenomas were compared with those in the 69 metachronous adenomas of the group 2 patients. It was found that male sex (P less than 0.005) and a history of colorectal neoplasia (P less than 0.02) are main factors for the development of new adenomas. The neutral mucins were less abundant in the group 2 index adenomas (r = -0.21; P less than 0.05). The expression of the other evaluated markers was not significantly different between both groups, although the group 2 index adenomas were significantly smaller (r = -0.22; P less than 0.05) and showed a trend toward a more pronounced cytoplasmic expression of carcinoembryonic antigen than the index adenomas from group 1 (22% vs. 12.5%). Moreover, it was found that in comparison with the index adenomas, metachronous adenomas were significantly smaller (r = 0.24; P less than 0.01) and more sessile (r = 0.20; P less than 0.002). Significant negative correlations, i.e., decrease, were also found in the expression of carcinoembryonic antigen (surface P less than 0.001; cytoplasmic P less than 0.05) and neutral mucins (P less than 0.005) between the index adenomas and the metachronous adenomas, whereas positive correlations were found for secretory component (P = 0.0001) and sulfomucins (P less than 0.05). These findings suggest that a limited production of neutral mucins in the goblet cells of a small index adenoma from a male patient with a history of colorectal neoplasia is indicative of an increased risk for the development of new colorectal adenomas. Furthermore, the clinical, mucin histochemical, and immunohistochemical findings of the metachronous adenomas show less malignancy associated features than those of the index adenomas. PMID- 1889716 TI - Epidemiology of colonic symptoms and the irritable bowel syndrome. AB - Functional gastrointestinal disease is believed to be very common, but reports of its prevalence have not usually evaluated random community samples, and validated questionnaires have not been used to elicit symptoms. The prevalence of specific colonic symptoms and the irritable bowel syndrome among representative middle aged whites was determined from a defined population, and the impact of these symptoms on presentation for medical care was measured. An age- and sex stratified random sample of 1021 residents of Olmsted County, Minnesota, aged 30 64 years, was obtained. All subjects were mailed a valid self-report questionnaire that identified gastrointestinal symptoms and functional gastrointestinal disorders. The response rate was 82% (n = 835). The age- and sex adjusted prevalence of abdominal pain (more than six times in the prior year) was 26.2 per 100 (95% confidence interval, 23.1-29.2). The prevalence of chronic constipation (hard stools and straining and/or less than 3 stools per week greater than 25% of the time) was 17.4 (95% confidence interval, 14.8-20.0), whereas the prevalence of chronic diarrhea (loose watery stools, and/or greater than 3 stools per day greater than 25% of the time) was 17.9 (95% confidence interval, 15.3-20.5). The prevalence of abdominal pain and disturbed defecation was similar in women and men, except that infrequent defecation and straining at stool were more common in women. Using the Manning symptom criteria to identify irritable bowel syndrome (greater than or equal to 2 of 6 symptoms in those with abdominal pain more than six times in the prior year), the prevalence of irritable bowel syndrome was 17.0 per 100 (95% confidence interval, 14.4-19.6). Overall, 71 persons (9%) reported visiting a physician for abdominal pain or disturbed defecation in the prior year; a subset of variables related to pain severity were the best predictors of health care seeking after adjustment for age and gender. However, these accounted for only 22% of the log likelihood. In conclusion, more than one third of an unselected middle-aged population reported chronic abdominal pain or disturbed defecation, and more than one in six had symptoms compatible with the irritable bowel syndrome. Only a minority had presented for medical evaluation; moreover, the characteristics of the abdominal complaints did not explain the seeking of health care in most cases. PMID- 1889717 TI - Action of beer and its ingredients on gastric acid secretion and release of gastrin in humans. AB - The intragastric action of beer and its known ingredients before and after fermentation on gastric acid secretion and release of gastrin was studied in healthy humans. None of 11 tested ingredients of fermented beer (2 x 500 mL, pH 5.5, given either alone or in combination) or hop extract had any significant effect. Finished beer (6 weeks old) and new beer were potent stimuli of acid output, causing 93% and 76% of the incremental maximal acid output in response to pentagastrin (6 micrograms/kg SC), respectively. Before the addition of yeast, preproducts of beer were considerably less potent. Thus, first and finished wort caused only a minor acid response which was 48% and 46% of maximal acid output. Foreign fermentation in first and finished wort is presumably the reason for the stimulatory action because glucose solutions in concentrations (11.5% wt/vol) seen in wort did not stimulate acid secretion. However, glucose solutions to which yeast was added, resulting in fermentation, were as potent stimuli of acid secretion as beer. Lyophilization of beer at pH 11.0 and dialysis (cutoff mol wt, 1000) removed the stimulatory substances. The plasma gastrin responses paralleled the gastric acid response to the different stimulants. It was concluded that (a) the addition of yeast to finished wort and the following alcoholic fermentation are the essential steps for the stimulatory action of beer on gastric acid secretion and release of gastrin; (b) carbohydrate metabolites with a molecular weight of less than 1000 are the acid-stimulatory agents in fermented beer; and (c) gastrin is the mediator of the stimulation of acid secretion because all substances that had a potent acid-stimulatory action also were potent stimuli of gastrin release. PMID- 1889718 TI - Omeprazole treatment does not affect the metabolism of caffeine. AB - This study was performed to investigate the possible influence of repeated omeprazole dosing on the metabolism of caffeine, which has been shown to reflect the activity of one specific enzyme within the hepatic cytochrome P450 family, P450IA2. Ten healthy, nonsmoking young men participated in this placebo controlled double-blind trial. Each subject was given omeprazole, 20 mg, every morning for 1 week and placebo every morning for 1 week in random order and separated by a 2-3 week washout period. On the sixth and seventh days of each period urine was collected twice daily, and urinary metabolites of caffeine were determined by high-performance liquid chromatography. The urinary metabolite ratio of three paraxanthine 7-demethylation products relative to a paraxanthine hydroxylation product corresponds to caffeine clearance and, therefore, to P450IA2 activity. This calculated ratio was 4.8 (95% confidence interval, 3.9 5.6) in the placebo and 4.6 (95% confidence interval, 3.6-5.5) in the omeprazole period. These results show that the metabolism of caffeine was unaltered following omeprazole treatment, indicating that omeprazole treatment has no influence on cytochrome P450IA2 activity in the clinical situation. PMID- 1889719 TI - Tolerance during 5 months of dosing with ranitidine, 150 mg nightly: a placebo controlled, double-blind study. AB - Repeated dosing with an H2-receptor antagonist results in a modest decrease in antisecretory potency termed "tolerance." The object of this prospective study was to determine whether tolerance is a progressive phenomenon or whether it levels off during prolonged dosing with a standard maintenance dose of an H2 antagonist. The effect of continuous dosing with ranitidine, 150 mg nightly, was compared with intermittent dosing (27 days of placebo each month) with active ranitidine, 150 mg nightly, only on the night of each experiment. Simultaneous 24 hour intragastric acidity and plasma gastrin concentration were measured monthly for 5 months in 17 healthy subjects (7 continuous and 10 intermittent dosing). In the intermittent-dosing group, the antisecretory response to ranitidine, 150 mg nightly, was preserved throughout the 141-day trial period; the median nocturnal integrated acidity decreased from 557 mmol.h/L (day 0) to 38 mmol.h/L on day 1 of dosing, and it ranged between 32 and 55 (median, 45) mmol.h/L during days 29-141. In the continuous-dosing group, there was a significant return of nocturnal intragastric acidity on days 29 and 85 compared with day 1 of dosing. The median nocturnal integrated acidity decreased in the continuous-dosing group from 554 mmol.h/L (day 0) to 87 mmol.h/L on the first day of dosing, and it ranged between 145 and 287 (median, 170) mmol.h/L during days 29-141. Either intermittent or continuous dosing with ranitidine was associated with an elevation of plasma gastrin concentration, which remained constant throughout the 5-month study. Tolerance does develop in healthy subjects during the first month of dosing with ranitidine, 150 mg nightly, but it is not a progressive phenomenon, and it is probably not of clinical relevance. PMID- 1889720 TI - Role of capsaicin-sensitive afferent neurons in alkaline secretory response to luminal acid in the rat duodenum. AB - The role of capsaicin-sensitive afferent neurons in acid-induced HCO3- secretion was investigated in the duodenum of anesthetized rats. The proximal duodenum was perfused with saline (pH 4.5), the pH of perfusate and the transmucosal potential differences were continuously monitored, and HCO3- output was determined by pH change. Under these conditions, duodenal pH, potential difference, and HCO3- output were significantly increased in response to IV injection of prostaglandin E2 (300 micrograms/kg) and luminal acidification (10 mmol/L HCl, 10 minutes). These responses induced by luminal acid were significantly attenuated by SC pretreatment with indomethacin (5 mg/kg), preexposure of the mucosa to lidocaine (4%, 15 minutes), functional ablation of capsaicin-sensitive afferent neurons, or even prior application of capsaicin (6 mg/mL, 30 minutes) to the duodenum. Although capsaicin application by itself (0.3-6 mg/mL) produced a concentration dependent increase of HCO3- output, this effect was significantly reduced by lidocaine, indomethacin, or chemical deafferentation and exhibited a tachyphylaxis after repeated application at a high concentration (6 mg/mL). Neither of these treatments significantly affected the HCO3- response induced by prostaglandin E2. It was concluded that stimulation of capsaicin-sensitive afferent neurons increased duodenal HCO3- secretion and that these neurons may be involved in the mechanism of HCO3- response induced by luminal acid in the duodenum. PMID- 1889721 TI - Reverse-perfused sleeve: an improved device for measurement of sphincteric function of the crural diaphragm. AB - The sphincteric function of the crural diaphragm has been difficult to measure in humans. The authors recently reported the use of a Dent sleeve device to measure esophagogastric junction pressure during contraction of the crural diaphragm. However, the major limitation of the conventional sleeve device is its slow response rate, and sustained diaphragmatic contractions of 6-8 seconds must be induced to measure the true pressure. In this article, the principles of a reverse-perfused sleeve device and the theoretical basis for its fast response rate are reported. The reverse-perfused sleeve is validated in an in vitro model of the lower esophageal sphincter. Furthermore, in vivo studies were performed in seven healthy human subjects. Standardized Muller maneuvers and straight-leg raises were performed to induce diaphragmatic contractions. Pressure increases of 50-150 mm Hg during diaphragmatic contractions were attained in less than 1 second. The delay between the actual contraction of the diaphragm as measured by simultaneously recorded crural diaphragm electromyography and pressure recorded by the sleeve was only 0.25-0.50 seconds. Increasing the rate of infusion of the sleeve from 0.5 to 1.0 mL/min did not further improve the response rate of the reverse perfused sleeve. It was concluded that the reverse-perfused sleeve is a considerable improvement over the conventional sleeve for quantitating the sphincteric function of the crural diaphragm. The role of the crural diaphragm in reflux esophagitis may be easily investigated using a reverse-perfused sleeve device. PMID- 1889722 TI - Effect of age on gastric acid secretion and serum gastrin concentrations in healthy men and women. AB - The effects of age on basal, meal-stimulated, and human gastrin-17-stimulated gastric acid secretion rates and serum pepsinogen concentrations were evaluated in 41 healthy men and women. Older subjects (ages 44-71 years; mean, 57 years) had higher mean basal, meal-stimulated, and gastrin-17-stimulated acid secretory rates and basal serum pepsinogen I and II concentrations than younger subjects (ages 23-42 years; mean, 33 years). Age-related differences in acid secretion were especially prominent in men, and age-related differences in serum pepsinogen I and II concentrations were more prominent in women. Higher gastric acid secretion rates in older subjects could not be explained by body size (height, weight, body surface area, or fat-free body mass) or by the higher incidence of infection with Helicobacter pylori. Using a multivariate linear regression model, age had an independent positive effect on acid secretion, and H. pylori infection had an independent negative effect. It was concluded that aging is associated with an increase in gastric acid secretion in humans, especially in men, while infection with H. pylori is associated with lower acid secretion rates. PMID- 1889723 TI - Enterogastric reflux after various types of antiulcer gastric surgery: quantitation by 99mTc-HIDA scintigraphy. AB - In 28 controls and 142 patients subjected to a variety of antiulcer procedures, the enterogastric reflux (EGR) was quantitated by 99mTc-HIDA scintigraphy and expressed as the EGR index on 229 different occasions. The EGR index was calculated according to two different formulas: one based on the maximal radioactivity over the gastric area as a percentage value of the total abdominal activity (EGR-Im) and the other based on the relative maximal radioactivity over the gastric area as a percentage value of the relative hepatobiliary activity (EGR-It). There was a significant positive correlation of values between the two methods (P less than 0.0001). In patients with an EGR-Im greater than 20% or EGR It greater than 57% and postgastric surgery symptoms some of the symptoms were attributed to EGR, an antireflux procedure is expected to relieve those symptoms. Sixteen of these patients underwent Roux-en-Y gastrectomy and their preoperative symptoms were relieved. PMID- 1889724 TI - The origin of symptoms on the brain-gut axis in functional dyspepsia. AB - It was hypothesized that symptoms in functional dyspepsia are originated by an altered mechanism at the brain-gut axis (one or several) in the process of gastric accommodation to a meal. To test the key mechanisms potentially involved in symptomatic gastric accommodation, the sensorial responses (on a 0-10 perception score) and the gastric tone responses (by electronic barostat) to either gastric accommodation (n = 10) or to cold stress (n = 10) were measured in 20 patients with functional dyspepsia and 20 healthy controls. The mechanical accommodation of the stomach to gastric distention (compliance) was similar in patients (52 +/- 8 mL/mm Hg) and controls (57 +/- 6 mL/mm Hg). However, isobaric gastric distention elicited more upper abdominal discomfort in dyspeptics than in controls (perception scores, 4.7 +/- 0.9 vs. 1.1 +/- 0.5, respectively; mean +/- SE; P less than 0.005). Cold stress induced a similar gastric relaxatory response in dyspeptics and controls (delta vol, 145 mL +/- 40 mL vs. 141 mL +/- 42 mL, respectively); hand perception (scores, 8.3 +/- 0.4 vs. 7.9 +/- 0.4, respectively) and autonomic responses were also similar. It is concluded that an abnormal afferent sensorial pathway (altered gastric perception) may be a major mechanism of symptom production in functional dyspepsia. PMID- 1889725 TI - [What benefit and harm can be expected from screening and routine examinations and from their omission?]. AB - Benefit and harm of screening and routine tests or their omission are dealt with in four parts. In the first part methods are described to evaluate the diagnostic value of medical testing. The concepts of diagnostic sensitivity, diagnostic specificity, and pre- and posttest probability of a diagnosis are defined. It is then shown how these concepts intercorrelate and how their numerical values can be calculated ("Bayes" theorem"). In consideration of the above mentioned intercorrelations, the second and third parts deal with the diagnostic value of preoperative routine tests from an anaesthesiological viewpoint, and the diagnostic value of other screening and follow-up tests is discussed from a gynaecological point of view. Pre-operative laboratory tests are necessary, and necessary only then, if careful evaluation of patient history and physical examination reveal pathological findings or risk factors. The benefits from regular lab-screening tests and follow-up tests, as recommended to the gynaecologists, are low. This is due to the large share of "healthy" women among the gynaecological patients, as well as the fact that treatment of early detected recurrences shows no demonstrable advantage over treatment of later detected recurrences. In the fourth part, we show that no adverse forensic consequences are to be expected if diagnostic tests are omitted because of demonstrably low diagnostic value. In case of legal procedures against the physician, a medical expert will have to evaluate the diagnostic value of the omitted test objectively from an "ex-ante" point of view, using the methods defined in the first part.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1889726 TI - [Clinic interns, individual performance appraisal and obstetric quality assurance]. AB - Obstetrical management and fetal outcome were individually analysed annually from 1987 to 1990, using computerised equipment. The individual results were discussed anonymously with all colleagues, but every colleague knew his own results. Clinical methods and obstetrical management had not been changed during the investigation period. The number of high-risk pregnancies increased significantly, whereby the incidence of risk-related surgical interventions decreased at the same rate. The number of FBA and EDA increased significantly (p less than 0.001). The mean umbilical artery pH increased during the last four years from 7.27 to 7.30 (p less than 0.05), i.e. that each colleague achieved an improvement. The incidence of acidotic values in the umbilical artery decreased significantly (pH less than 7.20 from 13.2% to 7.1%, pH less than 7.10 from 3.6% to 1.2% p less than 0.01). The rate of caesarean section increased (p less than 0.05) and the number of vaginal operative deliveries did not change significantly. As early as one year after the introduction of the individual efficiency control, a significant improvement in obstetrical results could be demonstrated. PMID- 1889727 TI - [The kinetocardiotocogram--initial clinical experiences using the kinetocardiotocogram]. AB - 160 woman patients in whom the course of pregnancy was uneventful or pathological (intrauterine growth retardation, percentile less than 5) were investigated at the Department of Obstetrics and Gynaecology of the University of Homburg/Saar between the 28th and 42nd week of pregnancy, using a newly developed cardiotocograph (HP M1350A Hewlett-Packard, Boblingen, FRG). By means of the kinetocardiotocogram (KCTG), fetal mobility (fetal movements of the whole body or of the extremities) was recorded simultaneously with the conventional recording of the fetal heart rate and uterine contractions. One of the aims in developing the KCTG was to record as far as possible all fetal movements synchronous to the recordings of heart rate and uterine contractions. To this end, the recording algorithm of the KCTG was adapted to the examination results obtained by two simultaneously operating ultrasound investigators. After the 28th week of pregnancy it was possible to record by the KCTG fetal "movement clusters" (combined body and limb movements) independent of the weight of the fetus and of amniotic fluid volume or positional anomalies, reliably and with good correlation with the results of the sonographic control investigations (r = 0.88-0.97). In cases of intrauterine growth retardation (percentile less than 5) a significantly reduced motility was observed on average as early as 13 days before delivery (p less than 0.005). It must be emphasized that, at this stage, most of the antenatal CTGs were normal. These findings indicate that KCTG can contribute to improved monitoring in high-risk pregnancies. PMID- 1889728 TI - [Clinical experience and possibilities of rapid cytogenetic diagnosis of spontaneous abortions in the routine work load of a gynecology clinic]. AB - The practicability of rapid karyotyping of spontaneous abortions by short-term culturing of chorionic villi is demonstrated in a large clinical study. 836 samples from spontaneous abortions were karyotyped successfully. Pathological findings were found in a rate of 48.8% whereby 54% of these were observed in week 10-11 of pregnancy. With increasing maternal age, the frequency of abnormal karyotypes also increased. Most of the pathological findings were trisomies, followed by polyploidies and monosomies. Correlation between maternal age and the type of aberration was observed. Chromosomal normal abortions were dominated by 46,XX abortions. The advantage of the described method of rapid karyotyping is the fact, that by knowing the karyotype of an abortion, a suitable concept of therapy can be chosen. Furthermore, a quick diagnosis has a positive effect on the psychological state of a patient, following a spontaneous abortion. PMID- 1889729 TI - [Effects of primary radiotherapy on uterine circulation in advanced cervix cancer]. AB - We examined 11 patients suffering from advanced cervical carcinomas, who were treated primarily with radiation. The blood flow through the uterus was established by measuring the Doppler pulse flow through the arteria uterina before and after radiotherapy. In a reference group of 25 women, free from cervical carcinomas, we established a median PI of the arteria uterina of 3.52 (+/- 1.10) with values between 1.64 and 5.06. In contrast, the group of 11 patients suffering from inoperable cervical carcinomas, were found to have a PI of 1.80 (+/- 1.40), with values between 0.41 and 4.41 (Wilcoxon Test: p = 0.001). After completion of the radiotherapy, 7 of the 11 patients showed no measurable pulsations of the arteria uterina, 3 patients had only systolic blood flow and only one patient had the same unchangingly high rate of blood flow as registered before radiotherapy. The significantly reduced flow of blood through the tumour tissue after radiotherapy, indicates a very limited response to chemotherapy. Therefore, chemotherapy should be administered before radiotherapy. PMID- 1889730 TI - [Vaginal sonographic contrast imaging of the endometrium with gel]. AB - In many cases, the sonography of the endometrium requires an exact pre therapeutical interpretation. Apart from a hysteroscopy, this can take place by means of an improved version of a contrast hysterosonography, i.e. the Gel-KHSG. The technique and examination results are described here. This simple examination method can--like hysteroscopy--precisely define or exclude anomalies of the endometrium, and, beyond that, it has the advantage of the sono-tomographic depiction of the uterine wall. Moreover, it can be taken assumed, that the vagino sonomorphological diagnostics at the endometrium could--for instance, analogous to the colposcopy of the uterine portion--become part of a system of preventive diagnostics for the cavum uteri. However, such a system has not been set up to date. PMID- 1889731 TI - [Differential diagnosis of cystic ovarian tumors by determination of estradiol in cystic aspirate]. AB - Since ultrasound is routinely used in gynecologic practice, cystic ovarian tumours are detected and, as a result, more unnecessary operations are performed. The aim of our study was, to determine the value of measurement of intracystic oestradiol (E2) in the differential diagnosis of simple cystic ovarian tumours. 30 patients, who underwent a laparotomy for cystic ovarian tumour, had prior measurements of E2 content of the cystic fluid. In 7 functional cysts, E2 was higher than 3,700 pmol/l and in the 23 neoplastic cysts, E2 level was lower than 1,200 pmol/l. Our results and the review of the literature suggest, that E2 content of the intracystic fluid may help to differ between functional and neoplastic cystic ovarian tumours. PMID- 1889732 TI - [Pregnancy after combined microsurgical and hysteroscopic surgical procedure in a patient with uterus septus and vagina septa]. AB - Disturbances in the development of the Mullerian duct system may cause different forms of genital anomalies. We report on a patient with uterus septus and vagina septa, undiagnosed for years, and consequently successfully treated for infertility, who became pregnant immediately after combined microsurgical and operative-hysteroscopic treatment. The pregnancy proceeded without any complications. The patient delivered a healthy girl in the 41st week of gestation. PMID- 1889733 TI - [Psoas abscess in pregnancy: a case report]. AB - Psoas abscess is a very rare complication in pregnancy. It creates difficulties in diagnosis and treatment. In our patient pain, fever, leukocytosis and Magnetic Resonance Imaging led to the diagnosis. It was the first manifestation of Crohn's disease. PMID- 1889734 TI - [Does an increase in endogenous estradiol in treatment with low-dose ovulation inhibitors signify increased risk?]. PMID- 1889735 TI - [Hysterosalpingography: synechia? Gartner's ducts?]. PMID- 1889736 TI - [64th Congress of the Bavarian Society of Obstetrics and Gynecology in Passau in the Nibelungen Hall 14-16 June 1990]. PMID- 1889737 TI - The giemsa banding pattern of canine chromosomes, using a cell synchronization technique. AB - Cytogenetic investigations of the domestic dog, Canis familiaris, were performed on the Doberman pinscher and two Boxer dogs. Conventional homogeneously stained and G-banded metaphases from peripheral blood lymphocyte cultures synchronized with amethopterin and bromodeoxyuridine were studied. These procedures permitted the unequivocal identification of all canine chromosomes. A canine chromosome idiogram was constructed on the basis of the G-banding pattern at the haploid 327 band resolution level. The secondary constrictions and tapering of the telomeric regions characteristic of several canine chromosomes are described. Q-, C-, and NOR-banding were also performed and the salient features are described. This karyotype should enhance the value of the canine species in cytogenetic investigations. PMID- 1889738 TI - The phylogeny of nine species of the Drosophila obscura group inferred by the banding homologies of chromosomal regions. I. Element B. AB - The phylogenetic relationships among nine Drosophila species belonging to the obscura group were investigated by establishing the segments displaying banding homologies in their element B (equivalent to the U element of D. subobscura). The phylogenetic ordering of the species was accomplished using overlapping inversions. Two African species, D. kitumensis and D. microlabis, were investigated. These species are homosequential for their element B gene arrangement but differ from that of D. obscura by several rearrangements. Drosophila obscura seems to be most closely related to D. subsilvestris, from which the respective element B gene arrangements differ at least by six inversions. Three species, D. obscura, D. ambigua, and D. tristis, are closely related and form a cluster. Drosophila obscura displays an element B polymorphism for a pericentric inversion for which D. ambigua is fixed for one gene arrangement and D. tristis for the other. Both D. ambigua and D. tristis share a short distal inversion in the small arm of the chromosome, and differ in this respect from D. obscura. Drosophila madeirensis, D. guanche, and D. subobscura all share the same element B gene arrangement, which is acrocentric, but metacentric in all the other species mentioned. It was found that the gene arrangements of the species from the obscura cluster seem to occupy an intermediate position between those of the species of the D. subobscura cluster and those of the African one. The data reported generally are in good agreement with information provided in the literature. PMID- 1889739 TI - DNA fingerprinting in reptiles: Bkm hybridization patterns in Crocodilia and Chelonia. AB - The simple tetranucleotide repeat GATA (GACA) occurs in all eukaryotes so far studied. In many species, the arrangement of these sequences varies considerably among individuals. Thus GATA (GACA) type probes produce DNA fingerprints when hybridized with restricted DNA from different individuals within a species. Banded krait minor (Bkm) satellite DNA (related to sequences originally recovered from the W chromosome of the banded krait and consisting essentially of a series of GATA repeats) is found in a wide spectrum of vertebrates and invertebrates. We used the Bkm 2(8) clone to evaluate the occurrence of this satellite in DNA from five species of Crocodilia and six species of Chelonia, including the sea turtles Chelonia mydas and Lepidochelys kempi. Well-resolved DNA fingerprints were obtained. Among the crocodilians, fewer restriction fragments were generated and fewer of the fragments were polymorphic, than among the chelonians, consistent with the view that the crocodilians are less divergent within species. The Bkm 2(8) clone can accordingly be used to advantage in individual, familial, and population studies, and perhaps in the evaluation of taxonomic relationships in these animals. This is of potential value in endangered species such as C. mydas and L. kempi. PMID- 1889740 TI - The interspersed DNA repeat conserved in water birds' genomes. AB - A putative old and ubiquitous interspersed DNA repeat family was identified from TaqI restriction, M13 cloning, and sequencing of the genomic DNA of a Mallard (Anas platyrhynchos), a Muscovy Duck (Cairina moschata), a Toulouse Goose (Anser anser), and a Black Swan (Cygnus atratus). A 425-bp consensus core sequence was obtained for the interspersed family. The 425-bp unit was about 2% of the avian genome and was found to be conserved in at least four genera of the order Anseriforme: Anas, Anser, Cairina, and Cygnus. PMID- 1889742 TI - Muscle opacity (mo), a new mutant gene in Xenopus laevis, linked to the rusty locus. AB - A new developmental mutant is described in Xenopus laevis (Amphibia, Anura): muscle opacity (mo). Homozygotes die at larval stage 48. The underlying defect, visible at stage 47, is a degeneration of cephalic musculature. The mo gene is linked to the rusty locus, with a map distance of 6.1%. PMID- 1889741 TI - Differential susceptibility to a trematode parasite among genotypes of the Mytilus edulis/galloprovincialis complex. AB - We show that parasitism by the trematode Prosorhynchus squamatus in parental and introgressed Mytilus edulis/galloprovincialis (Bivalvia) mussels occurs in individuals with a predominantly M. edulis genome. This result suggests that the restricted specificity of P. squamatus is dependent on genetic factor(s) present in M. edulis. Because of its strong pathogenic effects (i.e. total castration and possible death), this parasite may be a source of intense selection against M. edulis genomes when they are present in a site. As a consequence, it may favour the geographic extension of the M. galloprovincialis genome. Previous studies have indicated that, in hybrid zones, recombinant genotypes are more susceptible to parasitic infections than either parental genotype. We demonstrate that this is not the case for the M. edulis/M. galloprovincialis system, and that the parental genotype alone determines susceptibility. PMID- 1889743 TI - Conservation and evolution of the nucleus-encoded and chloroplast-specific ribosomal proteins in pea and spinach. AB - Two cDNA clones have been isolated from a lambda g11 cDNA library constructed with poly(A)+ mRNAs prepared from spinach seedlings. These nuclear cDNAs encode chloroplast (cp) ribosomal (r) proteins designated L24 and L40. These r-proteins have been identified in the cp 50S r-subunit by immunoblot analysis, amino acid (aa) composition and N-terminal aa sequencing. The L24 r-protein contains a central eubacterial homologous core with the N- and C-terminal polypeptide extensions. The L40 r-protein has no homologous counterpart in bacterial ribosomes. The two nuclear encoded r-proteins have their homologues in pea, a legume, showing that specific elements of cp ribosomes are conserved in higher plants. Surprisingly, the cp-specific r-protein L40 has a higher aa substitution rate than that of other eubacterial-like cp r-proteins identified previously in pea and spinach. PMID- 1889744 TI - Modulation of firefly luciferase stability and impact on studies of gene regulation. AB - Two of the reporter enzymes most commonly used in studies of eukaryotic gene expression are chloramphenicol acetyl-transferase (CAT) and firefly luciferase (Luc). CAT has a half-life of about 50 h in mammalian cells, making it useful for transient transfection assays but less suitable for assays with stable cell lines. Luc has a half-life of only 3 h in mammalian cells, making it much more responsive in stable cell lines. Luc instability arises from its sensitivity to proteolysis both in vivo and in vitro. Compounds that resemble its natural substrate, luciferin, act as effective competitive inhibitors in vitro. When these compounds (e.g., phenylbenzothiazole) are added to either prokaryotic or eukaryotic cells, more than tenfold increases in Luc activity can be observed. This increased activity results from a lower rate of degradation of the enzyme in vivo and can be mimicked in vitro as phenylbenzothiazole protects Luc from trypsin digestion while it has no effect on the rate of digestion of alkaline phosphatase. PMID- 1889745 TI - Structure and expression of the duck alpha-enolase/tau-crystallin-encoding gene. AB - In the duck, the glycolytic enzyme, alpha-enolase (alpha ENO) and the lens structural protein, tau-crystallin (tau CRY), are products of the same gene, an example of protein multi-functionality. We report that duck alpha ENO/tau CRY mRNA levels are developmentally regulated: alpha ENO/tau CRY mRNA levels in the lens increase over those in the liver by embryonic day 14 and, within the lens, are higher in the lens epithelium than in fiber cells. We determined the structure of the duck alpha ENO/tau CRY-encoding gene (alpha ENO/tau CRY), sequenced 1 kb of 5'-flanking region, and demonstrated that this region contains a functional promoter. The gene is 13 kb in size and is composed of twelve exons; the exon organization is identical to that of mammalian enolase-encoding genes. A fragment of 5'-flanking region (-803/+3) containing three CCAAT boxes and a TATA box was able to activate transcription of a heterologous reporter gene when transfected into cultured lens cells. However, in spite of greater quantities of alpha ENO/tau CRY mRNA and protein in the lens, the promoter was equally active in primary cultures of embryonic lens, liver and fibroblast cells. Since the cultured cells unexpectedly lost the restricted pattern of alpha ENO/tau CRY mRNA levels observed in vivo, evaluation of the promoter's tissue specificity was precluded. PMID- 1889746 TI - Characterization of the opposite-strand genes from the mouse bidirectionally transcribed HTF9 locus. AB - The mouse HTF9 locus contains two genes that are bidirectionally transcribed with opposite polarity from a shared CpG-rich island. Both genes were previously shown to be expressed in a housekeeping fashion in mouse. We have now determined the molecular organization of the genes over 12 kb surrounding the island. In addition, we show that the HTF9 locus resides in the proximal region of mouse chromosome 16. We have sequenced the cDNAs corresponding to both divergent transcripts. Both genes appear to code for novel proteins that are structurally unrelated to each other. Finally, we show that both genes are highly conserved and efficiently expressed in human cells. PMID- 1889747 TI - Evidence for three genes encoding class-I alcohol dehydrogenase subunits in baboon and analysis of the 5' region of the gene encoding the ADH beta subunit. AB - Five alcohol dehydrogenases (ADH; alcohol: NAD+ oxidoreductase; EC 1.1.1.1) have been identified in the baboon. All are homodimers of five distinct ADH subunits, with the two class-I ADH subunits being differentially expressed in the liver (the beta-subunit) and kidney. We have hybridized restriction-enzyme-digested baboon DNA to a 30-bp probe or a 337-bp DNA fragment, to reveal the presence of three genes encoding class-I ADH subunits in the baboon genome. This result was confirmed by the amplification of three different baboon ADH (bADH) nucleotide (nt) sequences, corresponding to exon 5 in the human gene encoding ADH beta (hADHB) from baboon DNA. Two of these sequences are identical to previously isolated liver and kidney cDNA nt sequences. These results are consistent with a phylogenetic analysis of the nt sequences of class-I hADH and bADH genes. Then, using primers based on the nt sequence of hADHB, we amplified a 336-bp DNA fragment, from genomic DNA, encoding the 5' region of the bADHB gene. In a 49-bp region of overlap, the nt sequence of this DNA fragment was identical to the sequence of a cDNA fragment amplified from baboon liver mRNA, whereas there were seven differences between this DNA fragment and the sequence of a cDNA amplified from baboon kidney mRNA. We used primer extension analysis to identify three adjacent transcriptional start points (tsp) for bADHB mRNA. Initiation of transcription at the most 5' bp leaves a 72-bp untranslated region. Examination of the sequence upstream from the tsp reveals a number of conserved putative regulatory sequence elements. PMID- 1889749 TI - Cloning and sequencing of the gilthead seabream (Sparus aurata) growth hormone encoding cDNA. AB - The cDNA clones encoding gilthead seabream (gsb) (Sparus aurata) growth hormone (GH) have been isolated from a cDNA library prepared from seabream pituitary gland poly(A)+ RNA. The cDNA library was screened using red seabream and rainbow trout GH cDNAs. The complete nucleotide (nt) sequence of gsbGH has been determined. The cDNA sequence codes for a polypeptide of 204 amino acids (aa), including a putative signal peptide of 17 aa. The 5'- and 3'-untranslated regions of the message are 55 and 236 nt long, respectively. The predicted aa sequence of gsbGH revealed 97% homology with red seabream GH, 95% with tuna GH, 85% with yellowtail GH, and 65% with rainbow trout GH. PMID- 1889748 TI - Problems encountered in detecting a targeted gene by the polymerase chain reaction. AB - We have investigated problems encountered when using the polymerase chain reaction (PCR) to detect recombinants in gene targeting experiments in which homologous recombination occurs between incoming DNA and an endogenous target sequence. The targeting system studied was designed to correct a human sickle cell beta-globin-encoding gene (HBBS) on human chromosome 11 by replacing the defective gene with incoming DNA carrying normal HBB sequences. Two sets of experiments were executed which led to the isolation of a clone of cells having the sickle-cell gene corrected. We found that a positive control system was essential to allow a real targeting event to be distinguished from various types of false positives that arise during the diagnostic PCR. PMID- 1889750 TI - Protein-binding A + T-rich motifs flank the duck beta A-globin enhancer. AB - The duck beta A-globin (beta GLB) enhancer DNA was analysed by footprinting for sites of specific binding of proteins extracted from duck erythrocytes. The results were compared with previously determined protein binding to the homologous region in chicken DNA. Two A + T-rich protein-binding sites, not recognized in chicken, were found at the 5'-end and the 3'-end of the duck beta GLB enhancer. The 5'-motif (designated BS-1; 5'-AAACAAAATGAA) binds proteins extracted from both embryonic and adult erythrocytes, while the 3'-motif (BS-2; 5'-ATAAACAAGGTC) binds protein from embryonic cells only. PMID- 1889751 TI - Isolation of a cathepsin B-encoding cDNA from murine osteogenic cells. AB - Cathepsin B-encoding cDNA (CTSB) clones have been isolated from a lambda gt10 library of a murine osteosarcoma by differential screening during a search for genes which are typically expressed during osteogenic differentiation in mouse mandibular condyles in vitro. Sequencing of the CTSB 3' end revealed that the isolated sequence contained an 825-bp 3'-noncoding region, the polyadenylation signal and the poly(A) tail. The enhanced CTSB expression during the early stages of the enchondral ossification-like process in mandibular condyles in vitro suggests that CTSB participates in the degradation of cartilage matrix prior to the synthesis of bone matrix proteins. PMID- 1889752 TI - Structure and expression of the human gene encoding testicular H1 histone (H1t). AB - The gene coding for the human H1t histone, a testis-specific H1 subtype, was isolated from a genomic library using a human somatic H1 gene as a hybridization probe. The corresponding mRNA is not polyadenylated and encodes a 206-amino-acid protein. Sequence analysis and S1 nuclease mapping of the human H1t gene reveals that the 5' flanking region contains several consensus promoter elements, as described for somatic, i.e., S-phase-dependent H1 subtype genes. The 3' region includes the stem-and-loop structure necessary for mRNA processing of most histone mRNAs. Northern blot analysis with RNAs from different human tissues and cell lines revealed that only testicular RNA hybridized with this gene probe. PMID- 1889754 TI - Reducing the risk of stroke: identifying patients to refer for carotid endarterectomy. AB - The most common causes of stroke are two diseases of aging: hypertension and atherosclerosis. Therefore, although stroke may occur at any age, the incidence is highest among the elderly population. Noninvasive efforts to reduce the risk of stroke in the elderly include control of hypertension and diabetes, smoking cessation, low-cholesterol dietary habits, and moderate exercise. Routine low dose aspirin also provides some protective effect. High-risk patients (with asymptomatic high-grade stenosis, TIAs, or prior stroke) should be considered candidates for carotid endarterectomy in the absence of contraindications to surgery. PMID- 1889753 TI - Cloning and characterization of the human ADH4 gene. AB - Human alcohol dehydrogenase (ADH) constitutes a set of isozymes and enzymes with different tissue and substrate specificities. The subunits are coded for by at least five gene loci, ADH1-ADH5. We now report the cloning and analysis of the human ADH4 gene coding for the class-II ADH with pi-subunits. The gene spans a region of 21 kb and is divided into nine exons and eight introns. The arrangement is the same as for all analyzed mammalian class-I genes, but the region covered is 50% larger than that in the human class-I genes. The nucleotide (nt) sequences of the exons, exon/intron boundaries and 5'- and 3'-untranslated regions were determined. The transcription start point (tsp) of the ADH4 gene was defined by primer extension and localized to a position 61 nt upstream from the ATG start codon. A TATA box and a CAAT element were identified by homology to consensus sequences for tsp. No DNA structures homologous to the glucocorticoid-responsive elements (GRE) present in the ADH2 gene were found in the upstream region of the ADH4 gene, but two structures with a 70% identity to the GRE consensus sequence were found at nonhomologous locations. The difference and the overall low degree of identity, 41%, of the upstream regions suggest different regulatory mechanisms for the class-I and class-II genes. PMID- 1889755 TI - Malignant tumors of the eye in geriatric patients. AB - The ocular tissues can be the site of a number of malignant tumors in adults and geriatric patients. In addition to posing a threat to the patient's life, these tumors can cause severe visual loss or blindness. Therefore, the primary care clinician should be capable of prompt diagnosis of the various malignant ocular tumors and be prepared to refer the patient for appropriate management. This article provides a photographic guide to the most common primary and secondary malignancies that can affect the eyelid, conjunctiva, intraocular structures, and orbit in the geriatric patient. PMID- 1889756 TI - Guidelines for prescribing psychoactive drugs in the elderly: Part 1. AB - Primary care physicians are usually the first to see elderly patients with emotional problems secondary to dementia and other psychiatric disorders. Because these problems often can be treated effectively, physicians should have a working knowledge of the guidelines for optimal use of psychoactive medications. Part 1 of this two-part article discusses general prescribing guidelines based on the pharmacokinetics of aging and provides specific information about benzodiazepines and antidepressants. Antipsychotics and other psychoactive agents used to treat the elderly are discussed in part 2 (page 52). PMID- 1889757 TI - Obesity: it's time to 'clean house'. AB - Inactive older patients are at high risk for overeating. Caring doctors can help them tune out temptation and trim down. PMID- 1889759 TI - Coping with hypochondriasis in older patients. PMID- 1889758 TI - Will affluent elderly prop up Medicare? PMID- 1889760 TI - [Modulation of anthracycline resistance by reserpine in P388 leukemia cells]. AB - The activity of reserpine and a possible mechanism by which it reverses the resistance to both doxorubicin and pirarubicin in doxorubicin-resistant P388 leukemia (P388/DOX) cells were examined in vitro. During 48 hr drug-exposure, the sensitivity of doxorubicin and pirarubicin were potentiated markedly when reserpine was present at the concentration of 1 microgram/ml, which is not toxic to P388 leukemia (P388/S) cells. However, reserpine had little effect on the cytotoxicity of doxorubicin and pirarubicin in the sensitive parent cell. Reserpine at 0.5-20 micrograms/ml increased intracellular accumulation of doxorubicin and pirarubicin in the drug-resistant cells. The potentiating action of reserpine was stronger when the cells were preincubated with reserpine within 30 min. Efflux of doxorubicin and pirarubicin was greater in drug-resistant cells compared to sensitive cells. This enhanced efflux of drug resulted in a decrease in the intracellular accumulation of doxorubicin in the drug-resistant cells. When the resistant cells were exposed to 2 micrograms/ml of reserpine, this enhanced efflux was blocked. A similar effect of reserpine on doxorubicin was seen with the efflux pattern of pirarubicin. From the measurements of drug uptake and efflux, it seems that like other multiple drug resistance modifiers, reserpine modulates anthracycline resistance by increasing intracellular accumulation of drug. PMID- 1889761 TI - [Biochemical and histopathological studies on a mouse brain ischemic model induced by bilateral carotid artery occlusion: comparison with the carbon monoxide inhalation method and other ischemic or anoxic models]. AB - Bilateral occlusion of the carotid arteries (BCAO) killed 52% of the male ddY mice (N = 86) and 77% of the ICR mice (N = 96) within 10 min, and the mean survival time of the ddY strain recorded for the 10 min was significantly longer than the time of the ICR strain. Among animals that survived longer than 1 hr after BCAO, some (5 of ddY and 3 of ICR) were able to survive for more than 24 hr. All of the neurobehavioral and histopathological signs developed by BCAO and in most cases followed by death were found to be also inducible by unilateral occlusion alone, although this was in a small fraction of mice. The brain levels of ATP, glucose and acetylcholine significantly decreased in mice that died within 10 min after BCAO, while none of these changes were detectable in mice surviving BCAO for 1 hr, just as in mice that died by carbon monoxide or ether inhalation. The results obtained herein indicate that mice may not be homogeneous in the functional level of the collateral route of blood supply to the brain tissue and/or in the sensitivity toward the ischemia-inducible lethality. PMID- 1889762 TI - [Effects of low molecular weight heparin (FR-860) on the experimental disseminated intravascular coagulation models]. AB - Effects of low molecular weight heparin (FR-860) on experimental disseminated intravascular coagulation (DIC) models in rats were compared with those of conventional unfractionated heparin (UF-heparin) and other anticoagulants. In the endotoxin-induced DIC model, FR-860 (12.5-200 U/kg/hr) and UF-heparin (25-200 U/kg/hr) inhibited dose-dependently the decreases in platelet counts, fibrinogen, antithrombin III activity and alpha 2-plasmin inhibitor activity, and they also inhibited the increases in fibrin de-products and thrombus formation in the glomerular capillary bed. Neither gabexate mesilate (FOY, 10 mg/kg/hr) nor nafamostat mesilate (FUT, 0.1 mg/kg/hr) improved endotoxin-induced DIC. FR-860 showed comparable potency to UF-heparin in plasma anti-factor Xa (F.Xa) activity. However, FR-860 was weaker than UF-heparin in prolongation of activated partial thromboplastin time. In the thrombin-induced DIC model, both FR-860 and UF heparin significantly improved, as seen in the endotoxin-induced DIC model, the changes in coagulation and fibrinolytic parameters and suppressed the production of pulmonary thrombus. On the other hand, both FOY and FUT showed significant but weak improvement in this model. In addition, FR-860 inhibited the enhancement of fibrinolysis and the production of pulmonary thrombus in the lactic acid-induced DIC model. These results suggest that the efficacy of FR-860 on DIC in rats is comparable to that of UF-heparin and that the efficacy can be attributed to its anti-F.Xa activity. FR-860 can be expected to be a useful therapeutic drug for DIC. PMID- 1889763 TI - [Case histories and "medical statistics" 200 years ago--case notes by Jung Stilling on his cataract operations 1773-1778]. AB - At the time of Goethe, Jung-Stilling (1740-1817) was highly regarded for his cataract operations. He had a general practice in Elberfeld from 1772 to 1778 and began to carry out his eye operations there. Unpublished, handwritten notes on 92 cataract operations were found only a short time ago in the library of the University of Basle. These notes show us that Jung-Stilling wrote proper case histories that correspond somewhat to the style we use today. Apparently these notes, Report on my cataract cures and healing methods of other eye diseases, formed the basis for the statistical result he published in Marburg in 1791 that represent his main medical work: Methods of taking out cataracts and of healing... PMID- 1889764 TI - [Revision operations in retinal redetachment]. AB - We analyzed retrospectively 239 consecutive patients who had undergone reoperation for repeat retinal detachment; 441 repeat operations were performed. The average follow-up was 2.1 years, and on average we noted 1.8 retinal redetachments per patient. At the last follow-up examination in 173 eyes (72.4%), the retina was reattached; 10.5% of the eyes had a partially detached retina and in 15.9% the retina was again completely detached. Enucleation was necessary in 3 eyes (1.2%). Visual improvement occurred in 45% of the eyes with reattachment of the retina. When the first retinal detachment occurred, 74 eyes were aphakic. Compared to the other 165 eyes there was no difference in anatomic or visual outcome. Aphakic eyes needed fewer additional reoperations (39%) compared to the phakic group (50%, p less than 0.01). One important reason for the surgery being unsuccessful was poor placement of the scleral buckle. In both groups equatorial placement of the scleral buckle led to anatomical success in more than 50%. The eyes in the aphakic group required more vitrectomies (47%) compared to the phakic eyes (34%, p less than 0.01). PMID- 1889765 TI - [Development of lens opacities in a period of 6 months after pneumatic retinopexy]. AB - When performing a pneumatic retinopexy, air or gas is injected into the vitreous cavity to reattach a primary, rhegmatogenous retinal detachment. SF6 gas, for examples, remains in the vitreous cavity for up to 2 weeks before it is completely absorbed. It is conceivable that the injection of SF6 gas into the vitreous cavity interferes with lens metabolism, thus causing opacities of the lens. Even minor early changes in lens transparency can be monitored by Scheimpflug photography. Two months after performing a pneumatic retinopexy, 31 out of 100 consecutive eyes showed a loss of lens transparency, which was not pronounced or statistically significant. Six months after surgery the loss of transparency was more pronounced in all lens layers, increasing from the front to the back. The increment was statistically significant for the anterior lens cortex. Further investigations are needed to determine whether lens changes are the result of the intraocular tamponade with SF6 gas or are related to other factors, such as the surgical maneuver itself. PMID- 1889767 TI - [Postnatal cellular pleomorphosis in retinal pigment epithelium]. AB - Selected features of cell morphology of the retinal pigment epithelia (RPE) were compared in newborn (42 eyes) and adult albinotic rats (34 eyes) at the age of 9 months. The RPE of newborn rats was found to consist of nearly homeomorphous, hexagonal, mononucleate, and relatively small cells (monomorphism). Minimal regional differences were found to exist. In adult albinotic rats the density of the RPE cell population was found to be considerably reduced, but the cells and nuclei were generally enlarged. A high percentage of RPE cells was found to contain two nuclei, and as a rule there were always some cells with three, four or even more nuclei. The picture of the cell mosaic was characterized by marked pleomorphism with regionally determined graduation. Pleomorphous changes were more pronounced in the central than in the more peripheral areas. The genesis and dynamics of cellular pleomorphism are also discussed. PMID- 1889766 TI - [Comparative immunohistochemical studies of epiretinal membranes in proliferative vitreoretinal diseases]. AB - Epiretinal membranes are a fibrocellular tissue whose cellular components are macrophages, glial cells, retinal pigment epithelial cells and fibroblasts. In our immunohistochemical study on epiretinal membranes in proliferative vitreoretinopathy (PVR), proliferative diabetic retinopathy, macular pucker, uveitis and after intraocular silicone oil tamponade we analyzed the cellular growth patterns of these histogenetically different cell types on serial sections of paraffin-embedded and frozen material. In addition, the topographic distribution of fibronectin was analyzed and the localization of the epidermal growth factor receptor, which is the coreceptor for the transforming growth factor alpha, was examined by staining procedures. We used antibodies against macrophages (Ki-M7), cytokeratin, vimentin, desmin, glial fibrillary acidic protein and against the proliferation antigen Ki-67. The different cell systems often showed cell-type-specific growth patterns causing an "organoid" structure of the epiretinal membranes. Macrophages predominated in membranes of eyes affected by uveitis and after intraocular silicone oil tamponade. The coexistence of macrophages and other cell types within the same area might be explained by intercellular regulatory mechanisms. Fibronectin, which has functions that are important for cell adhesion, migration, proliferation and differentiation, was topographically localized mainly in areas of denser cell populations and within the walls of newly formed capillaries in diabetic membranes. There was no correlation with specific cell types, however. Among the cellular receptors necessary for signal transduction of mitogenic substances, we localized the coreceptor for the epidermal growth factor and the transforming growth factor alpha among actively proliferating macrophages in a PVR membrane.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1889768 TI - [Retinal changes in Wilson's disease]. AB - Increasing loss of vision caused by peculiar macroscopic and functional retinal changes was the first ophthalmologic manifestation of Wilson's disease in a 22 year-old patient. Neither retinal changes nor great visual impairment has been described thus far in the literature concerning this disease. Likely correlations are discussed with Menkes syndrome, an X-linked inborn error of copper metabolism with onset in early childhood. PMID- 1889769 TI - [Reference values for quantitative image analysis of indocyanine green video fluorescence angiography]. AB - Indocyanine green video-fluorescence angiography was performed in 46 healthy normal subjects between the ages of 20 and 81 years using a 30 degrees Zeiss fundus camera, an external light supply and a high resolution CCD camera. Pictures were directly stored in a picture analysis system based on a PC with a temporal resolution of 25 pictures per second. Using statistical picture analysis, choroidal blood-flow parameters were obtained in a round area of interest with a diameter of 8 degrees with the center in the fovea. The parameters include: the mean arterial filling time (AFT) and the mean capillary density (MCD) in the choroid. There was no correlation for one of these parameters with arterial blood pressure or intraocular pressure. All values for the AFT were on an equal level for normal subjects younger than 65 years. Older normal subjects in some cases had clearly increased arterial filling times. The density of the capillary network in the choroid was significantly reduced with increasing age, and there was reduced density of the capillary network in normals with myopia. PMID- 1889770 TI - Limbal transplantation for ocular surface reconstruction--a review. AB - Based on the new concept that the limbal epithelium contains the stem cell population for corneal epithelial cellular proliferation and differentiation, a surgical procedure, limbal transplantation, has been devised. This paper reviews the background information regarding how this procedure was originally developed and the encouraging clinical as well as experimental results of corneal surface reconstruction using this procedure. The clinical aspects are also discussed concerning the surgical indications, procedural details, expected results, and potential problems. We also include the recent results using a rabbit model to compare the efficacy of surface reconstruction between limbal transplantation and original conjunctival transplantation. We hope, through this up-to-date review, that our capacities to manage these and other ocular surface disorders will be enhanced by understanding the new important concept of the limbal stem cell. PMID- 1889772 TI - [Persistence of Chlamydia trachomatis in patients with chronic therapy refractory conjunctivitis]. AB - We report three patients with recurrent Chlamydia-associated conjunctivitis. The clinical course of the Chlamydial infection was documented by positive conjunctival smears (direct immunofluorescence staining) and the evaluation of the IgA-titer in the sera (immunoperoxidase assay). The recovery of the ocular symptoms after therapy onset correlated well with the negative results of the conjunctival smears and the decrease in IgA level in the sera. The recurrence of the conjunctivitis was accompanied by an increase in the IgA titer in the sera of all three patients and the presence of Chlamydial elementary bodies in the conjunctival scrapings in two cases. Three patients showed immunologic pecularities: two had an allergic diathesis; the third patient developed Wegener disease 3 months after the onset of ocular inflammation. Inclusion bodies or Chlamydial DNA can persist in conjunctival cells. Anderson suggested that a recurrence of active Chlamydial infection may be induced by external causes, which lead to reconstitution of elementary bodies from the persisting DNA. The extraordinary immune situation of our patients might be one cause of the recurrent conjunctivitis. PMID- 1889773 TI - [Results of 102 perforating pseudophakic keratoplasties]. AB - Between July 1980 and February 1990 we performed 102 penetrating keratoplasties in 102 eyes of 98 patients with pseudophakic bullous keratopathy. Patients were followed up prospectively with an average follow-up of 14 months. 53 of the implant were iris-supported lenses (ISL), 32 were anterior chamber lenses (ACL), and 17 were posterior chamber lenses (PCL) following extracapsular cataract extraction (ECCE). In 88 eyes the intraocular lens implantation had been performed elsewhere. The interval between lens implantation and keratoplasty ranged from 3 to 451 months (mean 59 months) and was significantly shorter (p less than 0.03) for PCL. Eight intraocular lenses had been removed before keratoplasty. During penetrating keratoplasty, 25 lenses were left in place, 49 were removed, and 20 were exchanged. Since 1988, PCL have been implanted and sutured to the iris after removal of the ACL or ISL in 17 eyes that had undergone intracapsular cataract extraction (ICCE). After keratoplasty, visual acuity improved in 95 of the 102 eyes. However, visual acuity was frequently limited by persisting cystoid macular edema. In eyes that had undergone keratoplasty following ECCE and PCL implantation, visual acuity was significantly better (p less than 0.03) and cystoid macula edema was rarer (p = 0.07) than in eyes with ISL or ACL. the prognosis of penetrating keratoplasty for pseudophakic bullous keratopathy is generally good, although visual acuity is often limited postoperatively by cystoid macular edema. The technique of secondary PCL implantation sutured to the iris appears promising for allowing better optic rehabilitation of patients with pseudophakic bullous keratopathy. PMID- 1889771 TI - [Conjunctival microcirculation and hemorheology in patients with venous occlusions of the retina]. AB - Forty-two patients with branch vein or central retinal vein occlusion were enrolled in this randomized placebo-controlled study. We studied the influence of hemodilution therapy with hydroxyethyl-starch (HAES-steril) combined with pentoxifylline (Trental) for 6 months. In the bulbar conjunctiva, capillary red blood cell (RBC) velocities and vessel diameters and rheological parameters of hematocrit, erythrocyte aggregation and plasma viscosity were examined. In the hemodilution group we observed no changes in vessel diameter and a significant increase in RBC velocity after therapy. After 6 weeks the RBC velocity showed 30% higher values but there was no statistically significant difference. After hemodilution therapy hematocrit, erythrocyte aggregation and plasma viscosity were significantly different from those in the control group. After 6 weeks we observed significant differences only in erythrocyte aggregation. This examination verifies the positive influence of hemodilution therapy on microcirculation and hemorheology. PMID- 1889774 TI - [Development of an improved cryopreservation vial for cryopreservation of donor corneas]. AB - To date, corneal cryopreservation has been performed in vials made of glass or plastic, where the cornea is placed in a large volume of culture medium. For improved cell survival, an attempt was made to define freezing curves, which are induced by variations in the temperature in the freezing chamber. Depending on the mass of the specimen to be frozen and on the material conducting the heat, the freezing vials used so far cannot be regarded as optimum. As glass and plastic do not conduct heat very well, we developed a new freezing vial that is especially suitable for corneal cyropreservation. In our experiments, the interaction of the chamber temperature and the temperature near the corneal endothelium were monitored. Additionally, endothelial cell survival was studied by postculturing the tissue and by vital staining. As a result, a cylindrical vial made of aluminum 2-4 mm thick was designed, which enables even heat transfer from the freezing chamber to the cornea. In this vial, the amount of freezing medium could be reduced to 400 microliters, so that the heat from the crystallization process was very low. In a small series the conditions that had been optimal with porcine tissue were tested on ten human donor corneas. The endothelial cell density before (2365 cells/mm2, range 1675-2800) and after cryopreservation (2199 cells/mm2, range 1600-2720) did not differ significantly. PMID- 1889775 TI - [Changes in the endothelial cell density after perforating keratoplasty]. AB - We examined 590 endothelial photomicrographs of 327 patients with computerized morphometry; these patients had undergone penetrating keratoplasty in the period from 1981 to 1987. We found a weak negative correlation of r = -0.39 between postoperative endothelial cell density and the postoperative period. The endothelial cell density in the interval 12-24 months postoperatively averaged 1624 cells/mm. This is approximately 380 cells/mm more than described in other studies of that kind. We found significantly higher cell densities for cultured corneas and for corneas of young donors (age up to 39 years) up to 1 year postoperatively. Comparison of the diagnosis groups showed no relevant differences in postoperative cell density. PMID- 1889776 TI - [Image of the cornea with the scanning laser ophthalmoscope]. AB - With a scanning laser ophthalmoscope (SLO), a hexagonal reflex phenomenon can be observed, which originates from the tear film and corneal tissue layers. Time motion analysis verifies that it is possible to discriminate between the cornea and tear film. PMID- 1889777 TI - [Capsular membranes: a risk factor for cataract operation?]. AB - A prospective study of the peroperative behaviour of eyes with pseudoexfoliation syndrome (PEX) in cataract surgery was carried out between June 1989 and July 1990, including 164 eyes with PEX and 164 eyes in the control group. All eyes underwent either phakoemulsifikation or extracapsular extraction with implantation of a posterior chamber lens. Intraoperative the eyes with PEX fairly often failed to reach adequate mydriases (23%) compared with the control group (5.5%). The rate of postoperative fibrinoid reactions was almost the same in both groups (7.9% in eyes with PEX, 7.5% in the control group). Even though the cataract extraction and implantation of the IOL sometimes is slightly more difficult due to inadequate mydriasis, there is no evidence for an increased rate of severe intraoperative complications. The incidence of ruptures of the posterior capsule and vitreous loss was 1.2% and 0.6% respectively in eyes with PEX, the former is within our results of cataract surgery, delivered from a study of 6000 consecutive cases from 1982 to 1985 (0.73%). PMID- 1889778 TI - [Experience with hydrophilic silicone disc intraocular lenses]. AB - When oxygen plasma was used for plasma etching it was possible to hydrophilize the surface of silicone intraocular lenses (IOLs) without changing the chemical composition or the properties of deeper layers of the polymer. The modification was characterized by surface analysis. (Electron spectroscopy = XPS, contact angle estimations) and by scanning electron microscope. A cytotoxic influence of the modified surface could be excluded by cell culture experiments in which we evaluated cell spreading, cell morphology, DNA synthesis and protein synthesis. In vivo experiments on rabbits showed that the postoperative foreign body reaction was not significantly influenced by the hydrophilization of the IOL surface. Over the entire follow-up period (12 weeks), there was a reduced tendency to induce posterior synechiae in the group with hydrophilized lenses (P = 0.009). The number of dislocations and the incidence of posterior opacification did not differ significantly; on the other hand there were indications of improved adhesion to the posterior lens capsule of the hydrophilized IOL. PMID- 1889779 TI - [Tarsus-plasty with chondroplasty]. AB - For a few years new Chondroplast has been available as a ready-to-use product in a variety of different shapes and sizes. The material is obtained from bovine cartilage and is made antigen-free and stable against decomposition by treatment with glutaraldehyde and irradiation. To date we have used Chondroplast for lid stabilization in 9 eyes with very slack entropion or ectropion. For tarsusplasty secondary to tumor resection we chose Chondroplast for seven eyes. A thin 0.5-mm thick lamella was cut out of the original material and positioned in a preformed pocket between the orbicularis muscle and the skin and conjunctiva and then fixed with Vicryl sutures. Corrective of eyelid malposition was combined with pentagonal excision for ectropion, or resection of the orbicularis muscle for entropion. In plastic lid replacement the material was sutured to the existing wound edges of the lid margin and covered posteriorly with conjunctiva and anteriorly with advancement or transposed flaps. In all patients the implant took well, and there were no complications during wound healing. The cosmetic and functional results were satisfactory. The largest post-operation follow-up time was over 1 year. In one case--1 year after resection of a lower eyelid basalioma- we had the opportunity to examine histologically the tissue in the area of a Chondroplast implant. We performed this biopsy excision because of a suspected recurrence. Macroscopically the implanted cartilage lamella was surrounded by a barely vascularized capsule. Histologically we found a non-vital cartilage implant surrounded by a mainly fibrotic connective tissue capsule. In only a few places was there evidence of a slight reaction to the foreign body but without substantial inflammation activity. There was also no histological indication of resorption of the implant. PMID- 1889780 TI - [A modified surgical approach to the orbits]. AB - A major precondition for microsurgical removal of an orbital tumor is adequate topographic preparation of the structures involved. Cosmetic aspects also have to be considered. In this regard, the modified surgical approach presented here is superior to the familiar techniques of lateral orbitotomy. The surgical steps are as follows: hemicoronal incision of the skin starting from the superior end of the external ear, extending into the hairy temporo-frontal region, and ending close in front of the hair line. This incision is performed through the periosteum down to the bone, so that the forehead skin flap can be exposed to give complete exposure of the temporal muscle and the entire bony borders of the orbit. Following the osteoplastic removal of the lateral orbital rim and wall, the periorbita is opened and the intraorbital tumor can be removed microsurgically all along the superior, lateral, and inferior regions of the orbit and the muscle cone even in the orbital apex. The postoperative functional and cosmetic results are good. PMID- 1889781 TI - [Development of postoperative motility in orbital floor, zygomatic and mid-face fractures]. AB - A prospective study of was made on 100 patients with fractures of the orbital floor, the zygoma and/or midface who were surgically treated and investigated (before and 3 days, 7 days, 1 month and 6 months after surgery) with regard to their eye motility (Hess screen) and their double vision (Harms tangent screen). Stable results were obtained at least 30 days after surgery. Patients in whom early surgery was performed (within 7 days after trauma) showed better results (82% improvement) compared with those operated on in the second week after the trauma (50% improvement) or later (27% improvement). Young patients (less than 10 years of age) and patients with midface fractures (LeFort II and III) showed significantly poorer results with regard to eye motility. PMID- 1889782 TI - [A modification for reducing measurement value spread with the Hertel exophthalmometer]. AB - The concave part of Hertel's exophthalmometer which contacts the orbita functions like an inclined plane. Therefore, the measurement is sensitive against tilting and changing of the basic distance. We modified this contact surface into a right angle. The tangents at the contact points form a common line at right angles to the measurement direction. Reproducibility of measurements was studied on 10 patients who were measured by 5 to 12 different examiners with both instruments. Accuracy improved significantly by 57%. PMID- 1889783 TI - [Differential expression of HLA DR, DP and DQ in cultivated, human ciliary body epithelial cells]. AB - The antigen-specific activation of T-helper lymphocytes is dependent on the presentation of antigen in context with the gene products of major histocompatibility complex class II (MHC II). Aberrant expression of MHC II on the ciliary epithelium has been observed in uveitic eyes, which may enable these cells to interact specifically with lymphocytes and may play a role in ocular autoimmunity. Human MHC II consists of three subclasses, termed HLA DR, DP and DQ, which seem to be differentially regulated and may have different functions. The present study was initiated to investigate the dynamics of the differential MHC II expression on cultured human non-pigmented ciliary epithelial cells (NPE cells) in response to gamma-interferon by means of immunohistochemistry. NPE were isolated by a technique of selective adhesion to tissue culture substrate, and growth was induced after transfection with an origin-defective mutant of SV-40 virus DNA. NPE grown in control tissue culture medium did not express MHC class II. HLA DR and DP could be induced by incubation with low concentrations of gamma IFN for short periods. HLA DQ was expressed only weakly even with higher doses of gamma-IFN and longer incubation periods. The differential expression of HLA DR and DP, compared to HLA DQ in response to gamma-IFN in the ciliary epithelium, is similar to observations in other non-lymphoid ocular cells, but appears to be different from the regulation of MHC II on lymphoid cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1889784 TI - [Clinical and experimental results with a new fully automatic self-tonometer]. AB - In a clinical study 25 patients being treated at the Department of Ophthalmology in the Hamburg University were instructed in self-tonometry using a new automatic tonometer. In a first sequence, three self-measurements were taken by the patients within 1 min; then a control measurement with a motor-driven hand applanation tonometer (HAT) was taken by a physician. The procedure was repeated 6-10 min afterwards without new local anesthesia. In addition, a dynamometer was applied to 5 healthy eyes in order to test the self-tonometer at higher pressure levels. The correlation of repetitive measurements of the self-tonometer showed good results for the patient measurements (r1 = 0.97, SD1 = 1.66 mmHg, r2 = 0.96, SD2 = 1.47 mmHg) and slightly worse values for the measurements with the dynamometer (r3 = 0.97, SD3 = 2.02 mmHg), probably due to the non-physiological deformation of the eye induced by the dynamometer. To establish accuracy, the results were compared to the HAT. The following results were achieved: (r1 = 0.97, s1 = 1.71 mmHg, r2 = 0.96, s2 = 1.49 mmHg, r3 = 0.97, s3 = 2.69 mmHg). Other studies with the self-tonometer will follow in order to optimize its accuracy and design. Self-tonometry under conditions of microgravity is planned for the 2nd German Spacelab Mission and the Russian Space station MIR. In the future, self-tonometry will play an important part in the management of glaucoma. PMID- 1889785 TI - [Follow-up of patients suspected of glaucoma using computer-assisted analysis of the optic disk]. AB - The Optic Nerve Head Analyzer was used for longitudinal monitoring of glaucoma suspects. Forty-one patients (76 eyes) were monitored for more than 12 months and 29 patients (51 eyes) for more than 18 months. A significant (p less than or equal to 0.06) decrease in the neuroretinal rim area was found in 8 of 51 eyes monitored greater than 18 months. Thirty-eight of 19 healthy subjects served as the control group. Only 1 of these 38 healthy eyes showed a significant decrease in the neuroretinal rim area (p = 0.04); this decrease is perhaps an artifact caused by the limited accuracy of the Optic Nerve Head Analyzer. From our data we conclude that longitudinal monitoring of patients for glaucoma by means of the Optic Nerve Head Analyzer is an adequate method of detecting ongoing glaucoma damage. PMID- 1889786 TI - ["Lateralis splitting" in total oculomotor paralysis with trochlear nerve paralysis]. AB - In two cases of 3rd nerve palsy and trochlear palsy we performed a new transposition procedure. This procedure consists of splitting of the lateral rectus muscle and transposition of the upper half to a retroequatorial point near the nasal superior vortex vein. The lower half is transposed to a retroequatorial point near the nasal inferior vortex vein. In the first case we linked the two halves with fascia late. The horizontal deviation was diminished by 15-20 degrees. PMID- 1889787 TI - [The scanning laser ophthalmoscope and its application as a measuring system for eye movements]. AB - This paper describes the present status of scanning laser ophthalmoscopy (SLO) for three-dimensional recordings of monocular eye movements. The measurement principle is based on tracking suitable landmarks on either the ocular fundus or the anterior eye pole. In addition, since it incorporates a special feature allowing the projection of visual test stimuli onto precisely controllable locations of the retina, SLO introduces a novel method of studying the relationship between retinal activity and eye movement analysis. The clinical use of SLO for the evaluation of vestibular otolith function by measuring the rotation of the ocular fundus image in response to lateral head tilt (ocular counterrolling reflex, OCR) is illustrated. PMID- 1889788 TI - [Value of diagnostic methods in conduction disorders for pacemaker indications and choice of a suitable stimulation mode]. AB - Sinus node syndrome: In patients with sinus node dysfunction, additional conduction disturbances may be present in the AV-node thereby precluding the possibility for basically-desirable atrial stimulation. Systematic electrophysiologic studies have shown that, overall, conduction disturbances are uncommon, albeit more frequently than in normal subjects and most are incurred a high rate of stimulation. In practice, invasive electrophysiologic studies are not required to clarify this question. If there is no high-grade AV-block on Holter monitoring, diagnostic atrial stimulation can be carried out at the time of pacemaker implantation via the atrial electrode. A low rate should be used initially then increased gradually. On 1:1 conduction to 130 to 140 b/min permanent atrial pacing is possible since under these conditions it is very unlikely that high-grade AV-block will occur. If AV-block is observed at an atrial rate of 130 b/min, an additional ventricular electrode for two-chamber pacing should be implanted. If there is intact retrograde ventriculo-atrial (V-A) conduction, isolated ventricular stimulation should not be carried out because of the possibility of hemodynamically-unfavorable pacemaker syndrome. Possible problems with intact V-A conduction currently have only negligible importance since the development of modern programmable two-chamber systems. Carotid sinus syndrome: On manipulation of the hypersensitive carotid sinus, the invariably present functional compromise of the AV-node is masked by the marked bradycardia but can be detected by atrial stimulation. This examination is not routinely necessary however, since in carotid sinus syndrome isolated atrial stimulation is not carried out.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1889789 TI - [Anti-bradycardia pacemaker therapy: rational choice of system in relation to hemodynamic and prognostic aspects]. AB - Currently, the most important indications for pacemaker treatment include high grade AV-block, the sinus node syndrome, atrial fibrillation with slow ventricular rate as well as the hypersensitive carotid sinus. In the Federal Republic of Germany, 88.5% of the units employed were fixed-rate ventricular single-chamber systems (VVI), in less than 10% dual-chamber systems (DDD) and in 2.4% fixed-rate atrial single-chamber systems (AAI) as well as rate-adaptive systems (VVIR, AAIR). In 1986, a total of 32,000 pacemakers were implanted in the Federal Republic and about 105,000 in the USA. State-of-the-art: Miniaturization of single-chamber systems to less than 20 grams and dual-chamber systems to less than 30 grams has been associated with markedly improved lead technology which has lowered energy requirements. The development of atrial-independent, variable rate systems has enabled rate adaptation in patients who are not candidates for DDD-stimulation or in whom the atrial rate is inadequate. With Holter functions various physiological parameters can be continuously monitored and their response as well as biorhythmicity are analyzed. INDICATIONS: The following guidelines are those of the working group "Cardiac Pacing" of the German Society for Heart and Circulatory Research for the choice of pacemaker systems which are considered to provide the best respective physiologic form of stimulation with the goal of rendering optimal hemodynamics. For characterization of the pacemaker modes, the five-letter NASPE/BPEG code is used. The possibility for single modes, AV synchrony and rate adaptation as central factors for physiologic stimulation forms is shown in Table 2. Those systems are designated as "physiologic" which reestablish AV-synchrony, that is, pacing modes in which the atria are incorporated With the VAT-, VDD- and DDD-modes there is an additional atrial triggered rate modulation. In AAI- order DDD/I-modes rate adaptation is independent of the atria (AAIR, DDD/IR) via physiologic parameters while rate adaptive VVI stimulation does not enable AV-synchrony. Atrioventricular conduction disturbances: Pacemaker treatment is carried out for prevention of Adams-Stokes symptoms and for improvement of the hemodynamic situation. Prognostic implications of pacemaker treatment: With pacemaker treatment the one year mortality of patients with Adams-Stokes symptoms and/or complete AV-block can be lowered to 5 to 19% from 50 to 70%.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1889790 TI - Hemodynamics and exercise capacity during pacemaker stimulation. AB - This review summarizes the present knowledge concerning the hemodynamic and myocardial effects of various pacing modalities with special reference to the importance of heart rate variability and atrioventricular synchronization. An adequate increase in heart rate, irrespective of atrioventricular synchronization, seems to be the most important denominator for cardiac output and exercise tolerance. Atrioventricular synchronization will add some hemodynamic benefit, which is most pronounced at rest. The importance of a rate adaptive atrioventricular delay and a normalized ventricular activation sequence remains, however, to be fully established. Myocardial oxygen consumption does not differ during fixed rate ventricular pacing, atrial synchronous or non synchronous rate-adaptive ventricular pacing, neither at rest nor during exercise, despite a higher cardiac output during the rate-adaptive modes. This indicates a more "economic" cardiac work with rate-adaptive pacing. Fixed rate ventricular pacing, on the other hand, may have negative long-term effects on myocardial function due to an increased cardiac sympathetic activity compared with rate-adaptive ventricular pacing, in particular during exercise. It is concluded that the majority of pacemaker-dependent patients will benefit from restored rate variability, with the atrial electrogram still being the most appropriate trigger for rate-adaptive ventricular pacing. When the atrial signal cannot be used or when it is unreliable, however, other rate-triggering signals can be used with comparable results regarding hemodynamics and exercise tolerance. PMID- 1889791 TI - [Which programmable functions of pacemakers are available, and what is their clinical relevance?]. AB - Microprocessors incorporated into cardiac pacemakers enable a substantial number of programmable functions (Table 1), the clinical relevance of which is the subject of this overview. Stimulation mode: The mode of operation can be chosen as fixed-rate, triggered and inhibited stimulation. Rate: Rate-programmability enables optimal setting with respect to electrophysiologic and hemodynamic considerations. Impulse amplitude and width: With programmable impulse amplitude and width excessive stimulation energy can be avoided and the duration of the aggregate prolonged. In some pacemakers, the output current can be chosen as "unregulated or regulated" whereby with regulated current the magnitude of the output impulse remains constant until the battery is depleted. Functional impairment of the pacemaker through threshold elevation or muscle stimulation can be eliminated by reprogramming of the impulse amplitude or width. Sensitivity: Programmability of the input sensitivity enables noninvasive counteraction of detection disturbances (as undersensing especially with low-amplitude atrial signals and oversensing of interference signals with subsequent pacemaker inhibition; Figure 1). A new option, automatic sensitivity setting, regulates the registration of cardiac activity at the atrial and/or ventricular level within a safety margin of 2:1; even though somewhat problematic, undersensing is rare. Electrode polarity: Depending on the clinical situation, the unipolar or bipolar electrode may offer advantages. The programmability of the electrode polarity accordingly represents a clinically-relevant new development which provides a favourable combination of bipolar detection and unipolar stimulation. Some modern dual-chamber systems enable separate programming of the atrial and ventricular electrode configurations. Hysteresis: For single-chamber systems and, more recently, AV-sequential pacemakers, hysteresis is optionally available, that is, a programmable prolongation of the basic interval after detection of a spontaneous cardiac event. With further refinement, the so-called search hysteresis prolongs the stimulation interval after a constant number of continuous stimulation cycles to a programmed hysteresis interval to allow spontaneous cardiac activity; if this is detected during the prolonged interval, the pacemaker is inhibited, otherwise the pacemaker stimulates at the set rate. An AV-interval hysteresis - to date only available in one pacemaker system - prolongs the duration of the AV-interval in the following cycles to a programmed interval, if, within the programmed AV-interval, spontaneous AV-conduction is detected. Additionally, after a defined number of AV-cycles an AV-interval prolongation is chosen to assess the possibility of physiologic AV-conduction. AV interval: Modern AV-sequential pacemakers incorporate integration of the differential and rate-adaptive AV-interval.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1889792 TI - The present status of cardiac pacing. AB - At the time of its inception, pacemaker treatment only had the goal of reliably maintaining a regular ventricular rhythm. After solving technical problems of detection, function and introduction of AV-sequential pacing (1962), cardiac hemodynamics have become the central issue of interest. While, at low heart rates atrial contraction contributes meaningfully to cardiac output, it has been shown that for physiologic needs and high rates, rate-adaptive single-chamber stimulation is hemodynamically more favorable than non-rate adaptive AV sequential pacing. A rate-adaptive stimulation, more suited to physiologic needs with incorporation of a combination of various control parameters will improve pacing technology in the future. Anti-tachycardia stimulation, now integrated into the function of the implantable cardioverter/defibrillator has substantially widened the scope of this aspect of pacing. PMID- 1889793 TI - [Anti-tachycardia stimulation in supraventricular and ventricular tachycardia with and without cardioverter/defibrillator]. AB - Reentry is the underlying electrophysiologic mechanism in most of the clinically occurring tachycardias. It has been known for 25 years that a reentrant circuit can be interrupted by correctly timed stimuli during programmed stimulation. Although there has been a continuous technological progress in pacemaker technology in the last ten years, application of pacemaker therapy for the treatment of atrial as well as of ventricular tachyarrhythmias did not increase significantly. Prophylactic permanent pacing preventing the onset of tachyarrhythmias has not become an accepted therapeutic approach and is still a matter of research. Antitachycardia pacing designed to interrupt a reentrant circuit uses single or multiple extrastimuli which invade the excitable gap of the reentrant circuit so that antegrade and retrograde conduction within the circuit becomes impossible. The excitable gap, however, is not a fixed electrophysiological parameter, but its width depends mainly on the influence of the sympathetic and parasympathetic nervous system. Therefore, a variety of stimulation programs delivered by the implanted pacemaker had to be invented in order to adapt to the constantly changing electrophysiologic parameters. It becomes obvious that application of burst stimulation is more effective than delivery of single or double extra stimuli and that tachycardia rate-related pacing is more reliable than fixed-rate pacing for tachycardia interruption. The most effective termination mode seems to be self-adaptive auto-decremental pacing with constantly decreasing intervals between multiple stimuli and addition of further impulses for each new termination attempt. The risk of acceleration of tachycardia or induction of non-clinical tachyarrhythmias is higher with burst stimulation than with single or double extra stimuli. Fast tachycardia rates are more prone to acceleration than slower ones. Tachycardia detection algorithms are based mainly on rate, sudden onset and rate stability of the tachycardia. In order to reliably distinguish pathologic tachycardias from sinus or physiologic tachycardias, other than rate-detection parameters will be applied in the future. These are endocardial electrogram signal-analysis, frequency content of the endocardial signals as well as biological sensors. A prerequisite for successful permanent antitachycardia pacing is a thoroughly performed preoperative electrophysiologic study in order to identify the most reliable and effective tachycardia termination mode. This requires multiple induction of the clinical tachycardia under various conditions, different activity or posture states as well as under the influence of antiarrhythmic drugs.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1889794 TI - Familial aggregation of lipids and lipoproteins in families ascertained through random and nonrandom probands in the Minnesota Lipid Research Clinic Family Study. AB - The familial aggregation of lipids [total cholesterol (CH) and triglyceride (TG)] and lipoproteins [high-density lipoprotein cholesterol (HDL) and low-density lipoprotein cholesterol (LDL)] was investigated in families ascertained through both random and nonrandom probands in the Minnesota Lipid Research Clinic Family Study. Nonrandom proband ascertainment was based on single selection through truncation for hyperlipidemia at an earlier screening. A path model was used to investigate the nature of familial resemblance using appropriate adjustments for ascertainment and to determine whether random and hyperlipidemic samples are heterogeneous with regard to the multifactorial model. The results suggest that parameter estimates are consistent with those from previous studies in which only random families were used and that random and nonrandom samples are homogeneous with regard to the path model for CH and LDL. However, for TG and HDL the random and hyperlipidemic samples are significantly heterogeneous. This heterogeneity would be observed if familial hypertriglyceridemia and/or familial hypoalphalipoproteinemia segregates predominantly in the hyperlipidemic rather than in the random sample, as on might expect. PMID- 1889795 TI - Fluctuating asymmetry as a possible measure of developmental homeostasis in humans: a review. AB - We investigate three hypotheses related to fluctuating asymmetry (FA) of bilateral morphologic traits in humans: (1) the magnitude of FA in individual suffering from different levels of morbidity is significantly elevated compared with FA in healthy control subjects, (2) FA is negatively correlated with an individual's heterozygosity, and (3) phenotypic variance of FA may have a significant genetic component (or at least a family resemblance). Our experimental data and the literature support the first hypothesis and indicate that individuals who suffer from chromosomal or polygenic morbidity and from anomalies or conditions of development with still unknown genetic components demonstrate an elevated FA of various structures. The literature regarding the second hypothesis is sparse but is generally in agreement with it, although some exceptions exist. A study of correlations of phenotypic scores of FA between family members of nuclear families in two independent samples has shown that FA variance in individual traits probably does not have any significant genetic component. However, phenotypic variance of the mean estimate of FA over 8 traits showed significant additive and nonadditive (dominance) genetic components, each about 0.30. PMID- 1889796 TI - Postmarital residence and within-sex genetic diversity among the Urubu-Ka'apor Indians, Brazilian Amazon. AB - The analysis of biologic variation in prehistoric human populations separately by sex has been used as a tool to recover post-marital residential rules. These studies, which focus on the sexual distribution of skeletal traits, assume that the degree of intragroup or intergroup biologic diversity is higher in one sex with regard to unilocality (uxori- or virilocality). Despite a recent attempt to interpret this phenomenon in terms of population genetics (Konigsberg 1988), the main assumption has never been tested in situations in which the real residential practice of an indigenous population is known and in which genetic rather than phenotypic data are available. We investigated the within-group and between-group genetic variability among males and females from 4 villages of an uxorilocal Amazonian tribe, the Urubu-Ka'apor, on the basis of 20 polymorphic loci. The results were only partly concordant with the expected. Individual mean per locus heterozygosities were not different between the sexes, and the analysis of genetic heterogeneity showed similar gene frequencies for males and females in all villages. On the other hand, the intergroup approach detected a level of variation significantly greater among females than among males. The ethnographic evidence shows that three of the four subgroups studied belong to the same gamic unity, with the fourth subgroup belonging to another gamic network. Within-sex differences in intergroup analysis turned out to be more evident; yet, when those 3 villages were investigated separately, the female FST (0.0609) proved to be significantly higher than the male FST (0.0218). Such results suggest that the intergroup analysis is more sensitive to the genetic effects of differential migration rates between the sexes. In prehistoric contexts, therefore, an intergroup genetic approach can provide more reliable grounds for sociocultural inferences. PMID- 1889797 TI - Relationship between birth order of spouses with different degrees of consanguineous relationship. AB - The relationship between birth order of spouses with different degrees of consanguinity is examined in a sample of 1826 couples belonging to the endogamous Vadde Fisherfolk of Kolleru Lake, Andhra Pradesh, India. We attempt to explain the wide variation in the frequency of different kinds of consanguineous marriages through the age-sex structure of the population in general and especially of the related families. This structure may also be manifested in the association between the birth orders of spouses. A highly significant and large correlation between the birth orders of spouses in uncle-niece marriages and a gradual decrease in the correlation with increase in remoteness of the relationship between the spouses were observed. Given the distribution of age differences between the spouses and assuming a standard age-sex structure, it seems possible to estimate the optimum frequency with which at least close consanguineous marriages occur in any particular population. PMID- 1889798 TI - Phenotypic evolution in prehistoric Ohio Amerindians: natural selection versus random genetic drift in tooth size reduction. AB - Many anthropologic investigations involve measurement and analysis of polygenic skeletal and dental traits in prehistoric populations from which genetic details cannot be inferred. However, population genetics concepts can be applied productively to analyses of phenotypic variation in prehistoric human populations. One potentially useful approach, derived from basic quantitative genetics (Lande 1976, p. 314), models the effects of natural selection and random genetic drift on the evolution of the average phenotype in a population. We apply this model to the problem of dental size reduction in three prehistoric Amerindian populations from Ohio. Conversion of mean log-transformed buccolingual diameters for six permanent teeth (maxillary and mandibular I1, M1, and M2) to phenotypic standard deviation units reveals significant size reduction in the maxillary teeth only. By assuming 40 generations (t) between the 2 populations and a narrow heritability (h2) range of 0.30-0.70, the estimated minimum selective mortality required to produce the reductions is 1.8 deaths per 100 persons per generation. Given the same t and h2 values, the effective population size (Ne) needed to reject the neutral hypothesis (i.e., random genetic drift) with 95% confidence is approximately 150. Because paleodemographic and ethnographic studies suggest minimum effective sizes of this magnitude for these populations, we tentatively reject random genetic drift and conclude that selective mortality is most probably responsible for the maxillary tooth size reduction observed. PMID- 1889800 TI - Inverse relationship between risk of SIDS and early neonatal mortality: study of state mortality rates. AB - It was predicted that at the state level early neonatal (0-6 days) mortality rates and rates for sudden infant death syndrome (SIDS) in the age range 7-364 days would be negatively correlated. Using published data for each of the 50 states and the District of Columbia over the 5-year period 1980-1984, the actual correlation was -0.68 (p less than 0.001). In a breakdown of early neonatal mortality by age at death, rates for infants aged less than 1 hour proved to be the exception; their rates were not found to be negatively correlated with the rates for SIDS (r = +0.20). This finding probably reflects uniformity in the quality of obstetric care. The geographic variation in mortality rates for infants aged 1 hour to 6 days might be explained by variation in the probability of a mother and fetus sharing one or more HLA antigens. PMID- 1889799 TI - Localized enamel hypoplasia of human deciduous canine teeth: prevalence and pattern of expression in rural Pakistan. AB - Localized hypoplasia of the labial surface of deciduous canine teeth is a widely reported enamel defect, the etiology of which remains enigmatic. Published frequencies for this defect are based on small or biased samples from prehistoric and clinical contexts. In this study I report the prevalence and pattern of expression of this defect among 113 schoolchildren of Harappa village, Punjab Province, Pakistan. The labial surface of deciduous canines of children between the ages of 5 and 8 years was examined using a penlight; age, sex, stature, and socioeconomic status were also recorded. The defect occurs in 34.5% of the subjects studied and in 14.6% of the teeth examined. No significant association was found between the presence of the defect and gender, socioeconomic status, stature, or side of the jaw. The hypoplastic lesion occurs more frequently in the mandible than in the maxilla, and bilateral expressions are less common than unilateral expressions. These results confirm specific aspects of earlier studies and imply that localized (circular) enamel hypoplasia of deciduous teeth, unlike linear enamel hypoplasia, is not a marker of systemic growth disruption. PMID- 1889801 TI - Sources of variation in longitudinal assessment of maximal aerobic power in teenage boys and girls: the Amsterdam Growth and Health Study. AB - Maximal oxygen uptake (VO2 max), generally accepted as a valid method for measuring state and change of aerobic fitness, was repeatedly measured in 93 males and 107 females 5 times over a period of 8 years. A direct measurement was made using a treadmill running test with constant speed (8 km/hr) and increasing slope. Oxygen uptake was analyzed continuously by an open-circuit technique. The reproducibility of VO2 max estimated from interperiod correlations resulted in high test-retest correlations of approximately 0.9 in both males and females. Inspection of the longitudinal data from the multiple-longitudinal design with four measurements in three cohorts did not reveal confounding effects, such as time of measurement effects, cohort effects, and drop-out effects. A comparison of the longitudinal data evaluated over four years with data from a comparable control group that was measured once during the four-year period also failed to show any testing effects. In 40% of the males and 50% of the females no leveling off in VO2 max could be demonstrated; that is, there was an increase of more than 150 ml in the last stage of running. A comparison of subjects who showed leveling off with those who showed no leveling-off supports the idea that in the age range 12-23 years leveling-off is not a prerequisite for reaching a true VO2 max. Repeated measurement of VO2 max, using a maximal running test on a treadmill appears to be a reliable method to describe the individual development of aerobic fitness in males and females in the age range 12-23 years. PMID- 1889802 TI - Genetic epidemiology of non-insulin-dependent diabetes mellitus in north India: preliminary analyses of some genetic markers in Punjabis. AB - Studies on monozygotic (MZ) twins and admixed populations show that the predisposition to non-insulin-dependent diabetes mellitus has a large genetic component. We have examined the distribution of some genetic polymorphisms (ABO, GLO, ESD, AK, ACPA, and GPI) in control and diabetic Punjabis from north India. The distribution of various genetic markers indicate that the differences between the control and diabetic samples are statistically not significant. Moreover, a contingency chi-square analysis over all loci suggests nonsignificant genetic differentiation (p = 0.50) between the Punjabi samples. PMID- 1889803 TI - Localization of the panhypopituitary dwarf mutation (df) on mouse chromosome 11 in an intersubspecific backcross. AB - Ames dwarf (df) is an autosomal recessive mutation characterized by severe dwarfism and infertility. This mutation provides a mouse model for panhypopituitarism. The dwarf phenotype results from failure in the differentiation of the cells which produce growth hormone, prolactin, and thyroid stimulating hormone. Using the backcross (DF/B-df/df X CASA/Rk) X DF/B-df/df, we confirmed the assignment of df to mouse chromosome 11 and demonstrated recombination between df and the growth hormone gene. This backcross is an invaluable resource for screening candidate genes for the df mutation. The df locus maps to less than 1 cM distal to Pad-1 (0.85 +/- 0.85 cM). Two new genes localized on mouse chromosome 11, Rpo2-1, and Edp-1, map to a region of conserved synteny with human chromosome 17. The localization of the alpha 1 adrenergic receptor, Adra-1, extends a known region of synteny conservation between mouse chromosome 11 and human chromosome 5, and suggests that a human counterpart to df would map to human chromosome 5. PMID- 1889804 TI - The Interleukin-6-dependent DNA-binding protein gene (transcription factor 5: TCF5) maps to human chromosome 20 and rat chromosome 3, the IL6 receptor locus (IL6R) to human chromosome 1 and rat chromosome 2, and the rat IL6 gene to rat chromosome 4. AB - Using two panels of somatic cell hybrids segregating either human or rat chromosomes, the gene encoding the interleukin-6-dependent DNA-binding protein, also called liver activator protein (designated transcription factor 5: TCF5), was assigned to human chromosome 20 and to rat chromosome 3. The TCF5 gene might be identical with the NF-IL6 gene. The locus encoding the IL6 receptor gene (IL6R) was localized to human chromosome 1 and rat chromosome 2. An IL6R-like (IL6RL) locus was also assigned to human chromosome 9. In addition, the rat interleukin-6 (IL6) gene was assigned to rat chromosome 4. These mapping data allow one to extend comparison between the rat, mouse, and human gene maps. PMID- 1889805 TI - Analysis of a dystrophin gene deletion by amplification of mRNA isolated from DMD myotubes cultured in vitro. AB - The most frequent causes for the X-linked muscular dystrophy of the allelic Duchenne (DMD) or Becker (BMD) type are partial deletions of the dystrophin gene. These mutations are accompanied either by disrupted or by preserved translational reading frames in mRNAs derived from the deleted genes. As a rule, the reading frame is destroyed in the more severe DMD, whereas it is preserved in the less severe BMD (M. Koenig et al., 1989, Am. J. Hum. Genet. 45, 498-506). We have analyzed in detail a deletion that was detected in a fetus at risk of DMD. The analysis of this mutation included the delineation of the altered subregion in the dystrophin mRNA. mRNA was isolated from myotubes derived from embryonic DMD myoblasts propagated in vitro. This study was based on enzymatic amplification by the polymerase chain reaction (PCR) of dystrophin mRNA and direct sequencing of the amplified cDNA. Exons 47 to 50 were found to be missing in the mRNA. The splicing of exon 46 to exon 51 resulted in a reading frameshift, indicating that this mutation is likely to be responsible for a DMD type of dystrophy. The clinical diagnosis of DMD for a 10-year-old patient in this family was compatible with the "reading frame" assumption. PMID- 1889807 TI - Chromosomal mapping of brain-derived neurotrophic factor and neurotrophin-3 genes in man and mouse. AB - Brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NTF3) are two new members of the nerve growth factor gene family, which play important roles in the development and maintenance of the vertebrate nervous system. Here we describe the assignments of the BDNF and NTF3 gene loci to human and mouse chromosomes and discuss the evolutionary relationship of human chromosomes 11 and 12. BDNF has been mapped to human chromosome 11p15.5-p11.2 and to mouse chromosome 2, and NTF3 to human chromosome 12p and mouse chromosome 6. PMID- 1889806 TI - Human and rat brain-derived neurotrophic factor and neurotrophin-3: gene structures, distributions, and chromosomal localizations. AB - The development and maintenance of the vertebrate nervous system depends upon neuronal survival proteins known as neurotrophic factors. Nerve growth factor (NGF) remains the best characterized neurotrophic molecule. Brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) are two recently cloned neurotrophic factors that are homologous to NGF. Here we describe the molecular cloning of the human and rat genes encoding BDNF, as well as the isolation of the human NT-3 gene. On the basis of comparison of our genomic and cDNA clones with those of previously isolated BDNF and NT-3 genes and cDNAs, we make inferences about the structures of processed transcripts derived from the neurotrophin genes and the protein precursors they encode. We demonstrate that the mature form of BDNF is identical in all mammals examined, and that the same is true of the mature form of NT-3. Furthermore, the respective tissue-distributions and neuronal specificities of NT-3 and BDNF are also conserved among mammals. Finally, we localize the gene encoding human BDNF (gene symbol designated BDNF) to chromosome 11, band p13, and the gene encoding human NT-3 (gene symbol designated NTF3) to chromosome 12, band p13. PMID- 1889808 TI - Linkage homogeneity near the fragile X locus in normal and fragile X families. AB - The fragile X syndrome locus, FRAXA, is located at Xq27. Until recently, few polymorphic loci had been genetically mapped close to FRAXA. This has been attributed to an increased frequency of recombination at Xq27, possibly associated with the fragile X mutation. In addition, the frequency of recombination around FRAXA has been reported to vary among fragile X families. These observations suggested that the genetic map at Xq27 in normal populations was different from that in fragile X populations and that the genetic map also varied within the fragile X population. Such variability would reduce the reliability of carrier risk estimates based on DNA studies in fragile X families. Five polymorphic loci have now been mapped to within 4 cM of FRAXA--DXS369, DXS297, DXS296, IDS, and DXS304. The frequency of recombination at Xq26-q28 was evaluated using data at these loci and at more distant loci from 112 families with the fragile X syndrome. Two-point and multipoint linkage analyses failed to detect any difference in the recombination fractions in fragile X versus normal families. Two-point and multipoint tests of linkage homogeneity failed to detect any evidence of linkage heterogeneity in the fragile X families. On the basis of this analysis, genetic maps derived from large samples of normal families and those derived from fragile X families are equally valid as the basis for calculating carrier risk estimates in a particular family. PMID- 1889809 TI - Construction and characterization of a NotI linking library of human chromosome 21. AB - Effective procedures have been developed for constructing NotI linking libraries starting from chromosome-specific genomic libraries. Fifteen different single copy and two rDNA NotI linking clones from human chromosome 21 were identified in two libraries. Their chromosomal origin was confirmed, and regional location established using hybrid cell panels. Hybridization experiments with these probes revealed pairs of genomic NotI fragments, each ranging in size from less than 0.05 to 4.0 Mb. Many fragments displayed cell type variation. The total size of the NotI fragments detected in a human fibroblast cell line (GM6167) and mouse hybrid cell containing chromosome 21 as its only human component (WAV17) were approximately 32 and 34 Mb, respectively. If these fragments were all non overlapping, this would correspond to about 70% of the 50-Mb content estimated for the whole chromosome. The linking clones will be enormously useful in the subsequent construction of a NotI restriction map of this chromosome. Characterization of these clones indicates the presence of numerous additional sites for other enzymes that recognize sequences containing CpG. Thus most NotI linking clones appear to derive from CpG islands and probably identify the 5' end of genes. PMID- 1889810 TI - Chromosomal assignment of the human genes coding for the major proteins of the desmosome junction, desmoglein DGI (DSG), desmocollins DGII/III (DSC), desmoplakins DPI/II (DSP), and plakoglobin DPIII (JUP). AB - We have established PCR assays for the genes coding for the major proteins of the desmosome type of cell junction, the desmosomal cadherins DGI (desmoglein) and DGII/III (desmocollins), and the plaque proteins DPI/II (desmoplakin) and DPIII (plakoglobin) and used them to test human-mouse and human-rat somatic cell hybrids with different contents of human chromosomes. From these data we were able to assign DGI to chromosome 18 (DSG), DGII/III to chromosome 9p (DSC), DPI/II to chromosome 6p21-ter(DSP), and DPIII to chromosome 7 (JUP). PMID- 1889811 TI - The conservation of dinucleotide microsatellites among mammalian genomes allows the use of heterologous PCR primer pairs in closely related species. AB - The high degree of polymorphism displayed by DNA microsatellites makes them useful as DNA markers in linkage studies. A search of the DNA sequence databases revealed that the locations of dinucleotide microsatellites are often conserved among mammalian species, enabling the prediction of the presence of DNA microsatellites using comparative genetic data. In closely related species such as cattle and sheep, this conservation was close enough to allow PCR primers designed for use in one species to be used to analyze microsatellite length polymorphism in the other. A total of 48 sets of primer pairs, flanking bovine microsatellites and giving polymorphic PCR products in that species, were tested with template DNA from sheep, horses, and humans. Specific products were obtained in 27 cases (56%) with ovine DNA, 20 of which (42%) showed polymorphisms. With equine DNA, 3 (6.2%) gave specific but monomorphic products, while no specific products were obtained using human DNA. The ability to use heterologous PCR primers, coupled with comparative mapping information will facilitate the use of DNA microsatellites in gene mapping studies in closely related species such as cattle and sheep, rat and mouse, or primates. PMID- 1889812 TI - Rapid screening of a YAC library by pulsed-field gel Southern blot analysis of pooled YAC clones. AB - A new method for screening of YAC libraries is described. Individual YACs were pooled into groups of 384 clones and prepared as samples suitable for pulsed field gel electrophoresis. A five hit human YAC library (Brownstein et al., 1989) containing approximately 60,000 clones was condensed into 150 such pools and chromosomal DNAs in each sample were separated on three pulsed field gels containing 50 samples each. Southern blots prepared from these gels were hybridized with probes of interest to identify pools containing homologous YACs. Further purification was performed using standard colony hybridization procedures. Twenty-one probes used thus far have identified 47 positive pools and corresponding YACs have been purified from 28 of these. Some significant advantages of this method include avoidance of DNA sequence analysis and primer generation prior to YAC screening and the ability to handle the entire library on three filters. The screening approach described here permits rapid isolation of YACs corresponding to unsequenced loci and will accelerate establishment of YAC contigs for large chromosomal segments. PMID- 1889813 TI - Application of methylase-limited partial NotI cleavage for a long-range restriction map of the human ABL locus. AB - The use of partial restriction digests for mapping complex genomes by pulsed field gel electrophoresis has been limited by the difficulty of consistently obtaining these digests in agarose, which is a necessary matrix for high molecular-weight DNA. Enzyme cleavage in agarose is faster then diffusion for most of the enzymes which cleave infrequently. We have developed a method for the production of partial digests in agarose for the endonuclease NotI (5' . . . GC/GGCCGC . . . 3') which circumvents the diffusion problem by using the blocking methylase M. BspRI (5' . . . GGmCC . . . 3'), which competes for the same sites. Using various ratios of the methylase and endonuclease results in partial digests in any size range desired. We report the successful application of this technique to the production of NotI partial digests of human genomic DNA for the mapping of the ABL locus of human chromosome 9. PMID- 1889814 TI - Microclones derived from the mouse chromosome 7 D-E bands map within the proximal region of the c14CoS deletion in albino mutant mice. AB - A group of radiation-induced perinatal-lethal deletions that include the albino (c) locus on mouse chromosome 7 causes failure of expression of various hepatocyte-specific genes when homozygous (S. Gluecksohn-Waelsch, 1979, Cell 16:225-237). The transcription of such genes could be controlled in trans by a regulatory gene(s) located within the proximal region of the C14CoS deletion. To identify this potential regulatory gene, a microclone library was established from microdissected D and E bands of chromosome 7. Three nonoverlapping microclones (E305, E336B, and E453B) hybridizing with wildtype but not with C14CoS/C14CoS DNA were isolated. E336B represents a single-copy DNA fragment, whereas E305 and E453B hybridized with 3 and 10 EcoRI DNA restriction fragments, respectively. All fragments map exclusively within the deletion. The microclones hybridized to DNA of viable C6H/C14CoS deletion heterozygotes but not to DNA of homozygotes for the lethal mutation c10R75M, which belongs to the same complementation group as c14CoS. DNA of viable homozygous mutant C62DSD, which carries a deletion breakpoint proximal to that of c6H, hybridized only with E453B. This microclone identified 6 EcoRI restriction fragments in C62DSD/C62DSD DNA. The results demonstrate that of the isolated microclones, E453B identifies a locus (D7RT453B) that maps closest to the hsdr-1 (hepatocyte-specific developmental regulation) locus (S. Gluecksohn-Waelsch, 1989, Mouse Newslett. 83: 149), which maps between the proximal breakpoints of deletions c10R75M and c62DSD. PMID- 1889815 TI - The gene map of the Norway rat (Rattus norvegicus) and comparative mapping with mouse and man. AB - The current status of the rat gene map is presented. Mapping information is now available for a total of 214 loci and the number of mapped genes is increasing steadily. The corresponding number of loci quoted at HGM10 was 128. Genes have been assigned to 20 of the 22 chromosomes in the rat. Some aspects of comparative mapping with mouse and man are also discussed. It was found that there is a good correlation between the morphological homologies detectable in rat and mouse chromosomes, on the one hand, and homology at the gene level on the other. For 10 rat synteny groups all the genes so far mapped are syntenic also in the mouse. For the remaining rat synteny groups it appears that the majority of the genes will be syntenic on specific (homologous) mouse chromosomes, with only a few genes dispersed to other members of the mouse karyotype. Furthermore, the data indicate that mouse chromosome 1 genetically corresponds to two rat chromosomes, viz., 9 and 13, equalizing the difference in chromosome number between the two species. Further mappings will show whether the genetic homology will prove to be as extensive as these preliminary results indicate. As might be expected from evolutionary considerations, rat synteny groups are much more dispersed in the human genome. It is clear, however, that many groups of genes have remained syntenic during the period since man and rat shared a common ancestor. One further point was noted. In two cases groups of genes were syntenic in the mouse but dispersed to two chromosomes in rat and man, whereas in a third case a group of genes was syntenic in the rat but dispersed to two chromosomes in mouse and man. This finding argues in favor of the notion that the original gene groups were on separate ancestral chromosomes, which have fused in one rodent species but remained separate in the other and in man. PMID- 1889816 TI - Highly clustered zein gene sequences reveal evolutionary history of the multigene family. AB - We have determined the nucleotide sequences of zein cDNA clones ZG14, ZG15, and ZG35. The three clones have 95 to 98% homology to the previously published sequence of clone A20, and 84% homology to sequences of the zein subfamily A30. Comparison of all sequences of the A30 and A20 subfamilies highlights the following features: the 5' nontranslated regions are 68 and 57 nucleotides in length for the A20- and A30-like mRNAs, respectively, and contain at least three repeats of the consensus sequence ACGAACAAta/gG; the majority of these genes are highly clustered as judged from pulsed-field gel electrophoresis of high molecular weight maize DNA. Furthermore, we discuss a model for the evolution of the multigene family which stresses the special importance of unequal crossingover and gene conversion in this system. PMID- 1889817 TI - Regional assignment of two genes of the human branched-chain alpha-keto acid dehydrogenase complex: the E1 beta gene (BCKDHB) to chromosome 6p21-22 and the E2 gene (DBT) to chromosome 1p31. AB - Maple syrup urine disease (MSUD) is caused by the deficiency of the mitochondrial branched-chain alpha-keto acid dehydrogenase complex. The multienzyme complex is a macromolecule (Mr 4 X 10(6] consisting of at least six distinct subunits. In this study, the human E1 beta gene (BCKDHB) has been localized to human chromosome 6 by hybrid somatic cell analysis, and regionally assigned to chromosome bands 6p21-22 by in situ hybridization. The E2 gene (DBT), which was previously localized to chromosome 1, is regionally assigned to the chromosome band 1p31 also by in situ hybridization. Localization of the E1 beta gene to chromosome 6p21-22 assigns another major human disease locus to a region that contains several important genes, including the major histocompatability complex, tumor necrosis factor, and heat-shock protein HSP70. Mapping of the E1 beta and the E2 genes may provide information for the linkage analysis of MSUD families with mutations in these two loci. PMID- 1889818 TI - Evidence for linkage of the central core disease locus to the proximal long arm of human chromosome 19. AB - Central core disease of muscle (CCD; MIM 117000) is a rare inheritable myopathy that is frequently found in association with susceptibility to malignant hyperthermia (MHS). This observation has prompted us to perform a linkage study in CCD families using various chromosome 19q probes that are linked to the MHS locus and map close to the ryanodine receptor gene (RYR1), a strong MHS candidate gene. Our genetic linkage data support a location of the CCD gene on proximal 19q13.1 and thus suggest that CCD and MHS may be allelic. PMID- 1889819 TI - Adaptation of the interspersed repetitive sequence polymerase chain reaction to the isolation of mouse DNA probes from somatic cell hybrids on a hamster background. AB - A strategy for the rapid isolation of DNA probes from radiation-fusion Chinese hamster cell hybrids containing overlapping portions of the murine X chromosome based on the interspersed repetitive sequence polymerase chain reaction (IRS-PCR) previously used with human somatic cell hybrids has been developed. This specific amplification of mouse DNA on a hamster background depends on the use of primers directed to the B2 short interspersed repeat element family and the R repeat, from the long interspersed repeat element family, L1. Two sets of amplification conditions, which gave specific amplification of mouse DNA from either a mouse X monochromosomal hybrid or irradiation-fusion hybrids having reduced X content, were defined. The mouse X-only chromosome hybrid yielded approximately 20 discrete reproducible bands, while the irradiation-fusion hybrids yielded between 1 and 10 discrete products. Comparison of different irradiation-fusion hybrids has allowed the definition of both specific and shared products corresponding to different regions within the overlapping X-chromosome fragments present within these hybrids. Use of such hybrids and the IRS-PCR technique has allowed the isolation of probes corresponding to the central region of the mouse X chromosome that contains the X-inactivation center. The method should be widely applicable to the isolation of mouse DNA sequences from mouse hybrid cell lines on either human or Chinese hamster backgrounds. PMID- 1889820 TI - Sequence of human glucose-6-phosphate dehydrogenase cloned in plasmids and a yeast artificial chromosome. AB - The sequence of 20,114 bp of DNA including the human glucose-6-phosphate dehydrogenase (G6PD) gene was determined. The region included a prominent CpG island, starting about 680 nucleotides upstream of the transcription start site, extending about 1050 nucleotides downstream of the start site, and ending just at the start of the first intron. The transcribed region from the start site to the poly(A) addition site covers 15,860 bp. The sequence of the 13 exons agreed with published cDNA sequence and for the 11 exons tested, with the corresponding sequence in a yeast artificial chromosome (YAC). The latter confirms YAC cloning fidelity at the DNA sequence level. Sixteen Alu sequences constitute 24% of the total sequence tract. Four were outside the borders of the mRNA transcript of the gene; all the others were found in a large (9858 bp) intron between exons 2 and 3. Two Alu clusters each contain Alus lying between the monomers of another. PMID- 1889821 TI - Generation of novel sequence tagged sites (STSs) from discrete chromosomal regions using Alu-PCR. AB - Human DNA segments from discrete chromosomal regions were generated by utilizing Alu-element-based polymerase chain reaction (Alu-PCR) of an irradiation-fusion hybrid containing approximately 10 to 15 Mb of human DNA. Following cloning into a plasmid vector, a subset of the clones was used to generate sequence tagged sites (STSs) de novo. By means of a panel of hybrids containing portions of the human X chromosome, the STSs were shown to localize to two chromosomal regions, Xq24-Xq26 and Xcen-Xq13, reflecting the presence in the irradiation-fusion hybrid of two human chromosome fragments. These results demonstrate that high densities of STSs can be rapidly and efficiently generated from defined regions of the human genome using Alu-PCR. PMID- 1889822 TI - Localization of the mouse thymidine kinase gene to the distal portion of chromosome 11. AB - We report the cytogenetic mapping of the thymidine kinase (tk-1) gene in the mouse using two complementary and independent analyses: (1) investigation of chromosome aberrations associated with tk-1 gene inactivation in the L5178Y TK+/- -3.7.2C cell line, and (2) fluorescence in situ molecular hybridization of cloned tk-1 cDNA probes to mitotic chromosomes of this cell line. The consensus location from both analyses is 11E1-E2. Consideration of the mouse tk-1 gene localization, along with evidence that the homologous human TK1 gene is located distally on the large arm of chromosome 17, appears to extend the region of homology between MMU11 and HSA17 to the distal end of both chromosomes. PMID- 1889823 TI - The gene for the novel vasoactive peptide endothelin 3 (EDN3) is localized to human chromosome 20q13.2-qter. AB - Endothelin 3 is a novel vasoactive peptide of unique structure and belongs to the endothelin gene family. Though it mainly functions as a vasoconstrictor/pressor, it plays a major role in a wide variety of other biological functions, possibly as a novel neuropeptide. Studies with human-mouse somatic cell hybrids have suggested that the gene EDN3 is localized on human chromosome 20. We confirmed this localization and regionally mapped the gene to the region 20q13.2-q13.3. PMID- 1889824 TI - Effect of Plumbago zeylanica root powder induced preimplantationary loss and abortion on uterine luminal proteins in albino rats. AB - P. zeylanica treatment during first 7 days of pregnancy abolished uterine proteins of 13,000, 19,000 and 26,000 and 75,000 Da molecular weights resulting in preimplantationary loss. Proteins having molecular weights 55,000 and 65,000 Da were absent in aborted rats, that were given P. zeylanica root powder since day 6 to day 17 of pregnancy. The results suggest that proteins having molecular weights 13,000, 19,000, 26,000 and 75,000 Da influence the implantation and proteins of 55,000 and 65,000 Da are required for the maintenance of the pregnancy. PMID- 1889825 TI - Goat erythrocyte calmodulin is not abnormal. AB - Calmodulin was purified from goat erythrocyte hemolysate using heat treatment and Sephadex G-100 gel filtration chromatography. The molecular weight and Stokes, radius of the purified calmodulin was determined. The goat erythrocyte calmodulin stimulated (Ca(2+)-Mg2+)-ATPase but not (Mg2+)-ATPase and (Na(+)-K(+)-Mg2+) ATPase. The (Ca(2+)-Mg2+)-ATPase of the erythrocyte membrane derived from human, rat, rabbit and pig were significantly stimulated. PMID- 1889826 TI - Effect of dihydroergotoxine, a cerebral vasodilator, on cognitive deficits induced by prenatal undernutrition and environmental impoverishment in young rats. AB - The study was conducted on 64 Charles Foster strain albino rats, which were equally distributed into 8 evenly matched groups, following a 2 x 2 x 2 factorial design, by varying three independent factors at two levels: nutrition--normal and undernutrition; environment--enrichment and impoverishment, and drug treatment- vehicle and dihydroergotoxine (3 mg/kg, i.p.). Prenatal undernutrition was induced by restricting the mother's food intake. The environmental enrichment/impoverishment and the vehicle/dihydroergotoxine treatments were given during the postweaning period of the pups. The rats were subjected to original and subsequent reversal brightness discrimination learning tests in a single unit T-maze at 8-9 weeks of age. Thereafter, the animals were tested for passive avoidance learning. The results indicate that undernutrition caused significant original and reversal discrimination learning, deficits whereas environmental deprivation attenuated only the original discrimination learning performance. Dihydroergotoxine treatment facilitated the learning performance of rats in both the original and reversal learning tests. Nutritional, environmental and dihydroergotoxine treatments had no effect on the retention of the passive avoidance learning, both at 24 hr and 1 week intervals. Dihydroergotoxine treatment attenuated the learning deficits induced by prenatal undernutrition. The results indicate that dihydroergotoxine is not likely to be useful in cognitive deficits, induced by malnutrition, though it facilitated learning acquisition, since it had no effect on retention. PMID- 1889827 TI - Antinociceptive action of GABA-mimetic agent--N-phthaloyl GABA. AB - N-phthaloyl GABA (P-GABA), a nonselective GABA-ergic drug, showed positive analgesic response in four different models in mice, viz-tail immersion, tail clip, hot plate and writhing-induced by acetic acid. Antinociceptive ED50 (ip in mice) of P-GABA was lowest in tail immersion method (ED50 = 24.27, mg/kg). Though pethidine (10 mg/kg, ip) significantly potentiated the antinociceptive action of P-GABA (20 mg/kg, ip), pretreatment of naloxone (5 mg/kg, im) did not influence the same. Pretreatment with atropine (10 mg/kg, im), picrotoxin (0.08 mg/kg) and 3-mercaptopropionic acid (2 mg/kg) reduced the antinociceptive action of P-GABA significantly. But pretreatment with bicuculline (0.4 mg/kg), a specific GABA antagonist, did not reduce the antinociceptive action of P-GABA. PMID- 1889828 TI - Modulation of morphine induced antinociception by intracerebroventricularly administered captopril. AB - Captopril when administered intracerebroventricularly (icv) in doses of 100, 300, 500 and 1000 micrograms induced a dose dependent antinociceptive effect in rats. Naloxone pretreatment (10 mg/kg, ip) completely antagonised antinociceptive effect of captopril, suggesting thereby the involvement of brain enkephalinergic system. Captopril 300 micrograms, icv potentiated the antinociceptive effect of morphine in intact animals. The bilateral adrenalectomy did not have any effect on this potentiation as against the reported blockade of potentiation in adrenalectomized animals when captopril was administered by systemic route. Thus potentiation of morphine induced antinociception by icv captopril is unlikely to be exerted through an effect on adrenal function and is most likely due to increased brain enkephalin levels. PMID- 1889829 TI - Effect of propranolol on ECG of Myna, Acridotheres tristis, and Goh, Varanus bengalensis. AB - Effect of propranolol (1 and 3 mg/kg body wt), a sympathetic blocking agent, on ECG patterns was studied in Varanus and Acridotheres. ECG was recorded before and after 5 min (immediate), 15 min and in some cases 25 min of drug infusion. All animals responded to propranolol with bradycardia. The effectiveness is dose dependent and it is also associated with the high heart rate both in Acridotheres and in Varanus. The P-R or P-S interval increased in all cases of Varanus after infusion. In Acridotheres height and duration of P-wave were increased slightly with the lower dose and decreased with the higher dose. The Q-S shortened with the lower dose and widened late with the higher dose in Varanus whereas in Acridotheres it is widened with lower and higher doses of propranolol. The Q-T interval has been increased in both groups of animals. An increased amplitude of T-wave height was observed in Varanus after 5 and 15 min of drug infusion. But it was noted with decrease in amplitude under high dose after 15 min of drug infusion. In Acridotheres it was on increase with lower dose and decrease with higher dose. The delta-wave disappeared after the administration of propranolol in Acridotheres.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1889830 TI - Antifungal activity and mode of action of saponins from Madhuca butyracea Macb. AB - The antifungal activity of saponins isolated as a byproduct from the defatted cake of M. butyracea oil seed is reported. The inhibitory concentrations against plant pathogenic fungi ranged from 500 to 2000 ppm. Maximum sensitivity to saponins was shown by Penicillium expansum. Cephalosporium acrimonium, Helminthosporium oryzae and Trichoderma viride. The saponins caused leakage of cell components and underwent degradation by fungus, Trichoderma viride. The usefulness of saponins as antimycotic agents is discussed. PMID- 1889831 TI - In vitro and in vivo inhibition of pulmonary cytochrome P450 activities by piperine, a major ingredient of piper species. AB - In vitro and in vivo modulation of drug metabolizing enzymes by piperine was investigated in microsomes of rats and guinea pigs. In vitro piperine caused concentration related inhibition (50% at 100 microM) of arylhydrocarbon hydroxylase (AHH) and 7-ethoxycourmarin deethylase (7ECDE) activities, which were comparable in control and 3-methylcholanthrene (3MC) treated rats. In guinea pig microsomes however, piperine caused strong inhibition at lower concentrations (35% at 10 microM) and relatively much lesser inhibition with further increase in piperine concentrations. A Dixon plot of the kinetic data of both AHH and 7ECDE indicated noncompetitive inhibition with a Ki of approx. 100 microM. In vivo, piperine given at a dose of 25 mg/kg body wt to rats caused a maximal inhibition at 1 hr of both the enzymes, while only AHH returned to normal value within 4 hr. Similarly, upon daily treatment of piperine (15 mg/kg body wt) to rats for 7 days, 7ECDE was consistently inhibited, while AHH showed faster recovery. Piperine thus appeared to cause differential inhibition of two forms of cytochrome P450 and thus would accordingly affect the steady-state level of those drugs metabolized by these pulmonary forms of cytochromes P450. PMID- 1889832 TI - Interrelation of xanthine oxidase and dehydrogenase and L-gulonolactone oxidase in animal tissues. AB - There is a correlation between phylogeny and the activities of L-gulonolactone oxidase (LGO), the key enzyme responsible for ascorbic acid (AH2) synthesis in animals and total xanthine oxidase and dehydrogenase [XOD(D/O)], the enzyme responsible for the production of endogenous superoxide radical (O2-.). LGO appears in the kidneys of amphibians and reptiles but livers of mammals. XOD(D/O) also is present mainly in the kidneys of amphibians and reptiles and livers of mammals. AH2 is a potential scavenger of O2-. and it appears that tissue specific expression of LGO takes place to counteract the endogenous O2-. toxicity. The interrelation of XOD(D/O) and LGO was also observed in the liver of rats during prenatal to postnatal development. PMID- 1889833 TI - Infectivity of a mermithid nematode Romanomermis iyengari (Welch) in different conductivity levels under laboratory and field conditions. AB - Infectivity of R. iyengari was examined by exposing mosquito (Culex quinquefasciatus) larvae to the preparasite at different conductivity levels. The preparasite infected 63.5, 30, 11, 1.5 and 0.5% of the mosquito larvae respectively at 2000, 2500, 3000, 3300 and 3600 mu ho/cm. Although, 62-69% of the preparasite survived at 4000-5400 mu ho/cm, it did not infect. Application of preparasite to tree-holes resulted in 53-63% infection of Aedes albopictus larvae initially. On 6th day the infection level was 40% which decreased further to 7% by 15th day. The infection reappeared on 38th day indicating that R. iyengari has not only infected mosquito larvae as soon as they were applied to tree-holes in which the conductivity was 600-2800 mu ho/cm but also got established there. PMID- 1889834 TI - Neurolytic manifestation of piscicidal flavanoid of plant, Engelhardtia colebrookiana (Lindle) in fish. AB - The sublethal concentration 6 mg.l-1 of a piscicidal flavanoid, 'Quercetin glycoside', obtained from E. colebrookiana affected neuro-architecture in medulla oblongata of freshwater fish, Barilius bendelisis (Ham.), at 32 days exposure. Since medulla of fish is primary centre for the reception of several incoming stimuli, the breakdown of neurons and their neuraxes in facial and vagal lobes impaired the transmission of sensory informations to cerebellum. Consequently fish became unconscious and could be caught easily with hands. The symptoms like lack of schooling, lack of response to food and external stimuli, sluggishness, incapability of maintaining body posture and uncoordinated functioning are accounted for by the neurolysis in hind brain of fish. PMID- 1889835 TI - Elimination of eggplant mottled crinkle virus using virazole in explant cultures of Solanum melongena L. AB - Virazole (1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide; 100 and 150 mg/l) incorporated into brinjal explant culture medium induced in complete elimination of eggplant mottled crinkle virus - Indian isolate (EMCV-1) from infected explant cultures of S. melongena L. and production of virus free plant progeny. Acridine orange and ethidium bromide (150 ml/l) were also potent antiviral agents to some extent. PMID- 1889836 TI - ComA gene encodes an ATP-dependent export protein for induction of competence for genetic transformation. PMID- 1889837 TI - NifA of Rhizobium meliloti is degraded by the products of genes lon, snoB and snoC in Escherichia coli. PMID- 1889838 TI - MCC located at 5q21 is most probably the colorectal tumor suppressor gene. PMID- 1889839 TI - Purification of renin and prorenin. PMID- 1889840 TI - Renin purification and cloning. PMID- 1889841 TI - Renin release regulation during acute renin inhibition in normal volunteers. AB - Blockade of the renin-angiotensin system by an angiotensin converting enzyme (ACE) inhibitor or an angiotensin II (Ang II) antagonist is accompanied by a reactive rise in renin release. This rise is generally attributed to interruption of the short feedback loop between Ang II and renin release. Similarly, after the administration of a renin inhibitor, the plasma concentrations of active and total renin are increased and plasma renin activity is suppressed. The aim of the present study was to investigate if a fall in the plasma Ang II level is the unique determinant of the rise in the active renin (AR) level that follows renin inhibition. Six normal male volunteers participated in three successive 240 minute experiments at weekly intervals according to a single-blind randomized Latin square design. For experiment 1, Ang II was infused at 2 ng/kg/min from 0 to 60 minutes and at 4 ng/kg/min from 60 to 120 minutes. For experiment 2, 0.3 mg/kg of the new potent renin inhibitor Ro 42-5892 was injected at 30 minutes followed by infusion at 0.1 mg/kg/hr from 30 to 240 minutes. For experiment 3, Ang II and Ro 42-5892 were administered simultaneously at the same doses as described above. The mean +/- SEM Ang II concentration increased from 10.2 +/- 1.6 to 33.7 +/- 11.2 pg/ml after infusion of exogenous peptide. It decreased from 9.5 +/- 0.9 to 1.4 +/- 0.3 pg/ml after the injection of Ro 42-5892 and increased from 15.6 +/- 2.9 to 37.1 +/- 11.8 pg/ml after the simultaneous infusion of both compounds.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1889842 TI - Prolonged angiotensin II antagonism in spontaneously hypertensive rats. Hemodynamic and biochemical consequences. AB - The present study examines the effects of prolonged angiotensin II antagonism in spontaneously hypertensive rats by using an angiotensin II receptor antagonist (DuP 753) that is devoid of agonistic properties and selective for the subtype 1 of the angiotensin II (AT1) receptor. The antihypertensive effects of DuP 753 and its effects on circulating parameters of the renin-angiotensin system were compared with those of a converting enzyme inhibitor (benazeprilat). To minimize any influence of differences in the pharmacokinetic properties of the two blockers, administration was by continuous intravenous infusion. The experiments were performed in conscious, freely moving rats with continuous 24-hour monitoring of blood pressure. DuP 753 (10 or 30 mg/kg/day) lowered mean arterial pressure to the same extent as benazeprilat (3 or 10 mg/kg/day) during a 48-hour period. The antihypertensive effect was sustained when the treatment was extended to 7 days (DuP 753, 10 mg/kg/day; benazeprilat, 3 mg/kg/day). Neither of the compounds affected the baseline or diurnal rhythm of heart rate. Plasma concentrations of renin and angiotensin II were increased sevenfold and 10-fold, respectively, in the rats treated with DuP 753. In rats treated with benazeprilat, plasma renin concentration increased threefold, whereas angiotensin II was unchanged. Heart weights were significantly reduced to a similar extent by DuP 753 and benazeprilat. Both compounds also induced a smaller but significant decrease in blood pressure in Wistar-Kyoto rats. Our results indicate that the antihypertensive effects of converting enzyme inhibitors in spontaneously hypertensive rats are mainly due to the blockade of the renin-angiotensin system. In this rat model, angiotensin II appears to play an important role in the maintenance of hypertension that is mediated via the AT1 receptor. PMID- 1889843 TI - Simplified captopril renography in diagnosis and treatment of renal artery stenosis. AB - To improve the diagnosis and forecast the response to surgery or renal angioplasty in patients with hypertension and renal artery stenosis, we employed a simplified captopril renography protocol in conjunction with renal arteriography in 94 clinically selected patients. Fifty hypertensive patients (group 1) with a high clinical likelihood of renovascular hypertension were evaluated using a simplified captopril renography protocol and renal angiography on the arterial side. Criteria for normal captopril renal scintigrams were established based on this original cohort and validated in an additional 44 clinically comparable patients (group 2). Renal revascularization or nephrectomy was performed in 39 patients, and success of the procedure was determined in the 34 patients for whom 3-month follow-up was available. In the 94 patients, 44 (47%) had renal artery stenosis. Simplified captopril renography was 91% sensitive and 94% specific in identifying or excluding renal artery stenosis in the combined group, with no difference in the diagnostic utility between groups 1 and 2, or in those with renal insufficiency (n = 38) or those with bilateral disease (n = 17). Scintigraphic abnormalities induced by captopril were strongly associated with cure or improvement in blood pressure control following revascularization or nephrectomy (15 of 18), while the lack of captopril-induced changes was associated with failure of such intervention (13 of 16) (p = 0.0004). We conclude that simplified captopril renography is highly sensitive and specific in the diagnosis of renal artery stenosis in a clinically selected high-risk population and that the test accurately predicts the success or failure of therapeutic intervention. PMID- 1889845 TI - Evidence for a renomedullary vasodepressor system in rabbits and dogs. AB - Renal perfusion was increased in anesthetized rabbits and dogs by using an extracorporeal circuit. When left kidney perfusion pressure was raised in rabbits (145-240 mm Hg), arterial pressure fell by 1.34 +/- 0.20 mm Hg/min. Pretreatment of the rabbits with 2-bromoethylamine hydrobromide, which destroyed the renal medulla, abolished the fall in arterial pressure (-0.08 +/- 0.08 mm Hg/min) in response to increased renal perfusion pressure. In dogs (with blockade of autonomic ganglia by pentolinium, converting enzyme inhibition [captopril/enalaprilat], and surgical renal denervation), increasing renal perfusion pressure to 170-220 mm Hg resulted in a fall in arterial pressure by 0.32 +/- 0.03 mm Hg/min (or by 28.9 +/- 3.1 mm Hg over a 90-minute period). Mean arterial pressure did not change significantly in identically prepared dogs not subjected to increased renal perfusion pressure, whereas pretreatment of dogs with bromoethylamine abolished the hypotensive response to increased renal perfusion pressure. Thus, the hypotensive response to increased renal perfusion was dependent on the presence of an intact renal medulla, but hypotension still occurred in the presence of converting enzyme inhibition, autonomic ganglion blockade, and renal denervation. The results provide in vivo evidence in two species that a vasodepressor factor from the renal medulla is released in response to increased renal perfusion. PMID- 1889844 TI - Diagnostic usefulness of renal scanning after angiotensin converting enzyme inhibitors. AB - Radioisotopic renal scanning after angiotensin converting enzyme inhibition (ACEI) has proven to be an exciting area for research. The biologic activity of markers such as DTPA and hippuran, when combined with the physiological effects of ACEI, may provide noninvasive methods of diagnosing both renal artery stenosis and renovascular hypertension. Recent investigators have demonstrated that the sensitivities and specificities of these tests may vary widely; these differences are probably due to variations in study design, patient population, diagnostic criteria, and outcome measurements. We have reviewed these studies and discuss these possible sources of variation and their impact on the clinical usefulness of these diagnostic tests, especially in relation to the prevalence of disease in the population. Current results suggest that the post-ACEI DTPA scan is relatively accurate in the diagnosis of renal artery stenosis, with sensitivity generally greater than 90% and specificity around 95%. However, the best results in predicting the response to angioplasty or surgery in patients with renal artery stenosis have been with the use of post-ACEI hippuran in combination with furosemide (sensitivity, 96%; specificity, 95%). With confirmation of these findings and continued investigation, it is expected that accurate noninvasive tests will be available for widespread clinical use in the near future. PMID- 1889846 TI - Renal changes associated with cyclosporine in recent type I diabetes mellitus. AB - The effects of cyclosporine A treatment on arterial pressure and renal function were assessed in 11 young patients with type I diabetes of short duration. Cyclosporine was started at 7.5 mg/kg/day, progressively decreased to 6.3 mg/kg/day at 6 months, and then continued at a lower dose (4.1 mg/kg/day) for an additional 3 months in patients in whom remission of insulin dependency was obtained (n = 6). After 3 months of cyclosporine, a slight but significant increase in arterial pressure (+5.2 +/- 1.5 mm Hg), a rise in renal vascular resistance (approximately 20%), a decrease in glomerular filtration rate (approximately 25%), and a fall in filtration fraction were observed. Such changes were sustained after 6 and eventually 9 months of therapy. The decrease in glomerular filtration rate observed during cyclosporine treatment contrasted with the lack of change in simultaneously estimated creatinine clearance; in fact, the creatinine clearance/glomerular filtration ratio increased from 1.07 +/ 0.05% to 1.33 +/- 0.09% within 3 months of cyclosporine therapy, thus suggesting an enhanced tubular secretion of creatinine. Plasma renin activity and urinary excretion of kallikrein decreased significantly (approximately 50%), whereas plasma aldosterone concentration remained unaltered and plasma concentration of potassium increased during cyclosporine therapy. These changes were observed in the presence of a constant urinary excretion of sodium and potassium and a constant body weight. All parameters returned to pretreatment values within 3 months after cessation of cyclosporine. These results indicate that cyclosporine given for 6-9 months at a moderate dose causes a deleterious but reversible effect on arterial pressure and renal function in young diabetic patients. PMID- 1889848 TI - Uptake of norepinephrine in an isolated artery from normotensive humans. AB - Previous studies have suggested that catecholamine uptake may play a role in vascular responsiveness in hypertension. The current study was undertaken to characterize amine uptake and effects of its inhibition in an isolated human artery from normotensive subjects and to provide a basis for future study in hypertensive individuals. Accumulation of tritiated norepinephrine into the artery of normotensive subjects was time-dependent and 16.9-fold more than the incubation media concentration (1 microM) of amine after 60 minutes. There was a lesser accumulation of tritiated normetanephrine (3.1-fold), and it was not increased over time. Increasing the concentration of norepinephrine to 30 microM did not significantly change the proportional accumulation. Inhibition of neuronal uptake with cocaine (10 microM) reduced the average accumulation of both concentrations of tritiated norepinephrine to 3.9-fold (p less than 0.001). Inhibition of extraneuronal uptake with corticosterone alone (10 microM) had no significant effect on average accumulation of norepinephrine, and where combined with cocaine, there was no further effect of corticosterone. Neither cocaine nor corticosterone had any effects on accumulation of normetanephrine. In spite of elimination of approximately 75% of the uptake of norepinephrine, cocaine had very little potentiating effect on mechanical responses to exogenous norepinephrine and neurally released transmitter. Thus, norepinephrine uptake in human cystic artery is characteristic of neuronal uptake, but cocaine treatment has only a very modest potentiating effect on responsiveness to endogenous norepinephrine and no significant effect on responsiveness to exogenous amine. PMID- 1889847 TI - Glucose tolerance and insulin action in rats with renovascular hypertension. AB - To test whether hypertension can cause hyperinsulinemia or insulin resistance, we performed intravenous glucose tolerance tests at 1 month and euglycemic clamps at 3 months after induction of two-kidney, one clip renovascular hypertension in rats. At 1 month, systolic pressure was higher in 21 clipped than in 12 control animals (161 +/- 5 mm Hg, range 134-187 mm Hg versus 119 +/- 3 mm Hg, range 108 146 mm Hg; p less than 0.001). Glucose tolerance, assessed as the glucose fractional disappearance rate between 3 and 11 minutes after the glucose injection, was similar in the clipped and sham groups (0.059 +/- 0.002 versus 0.056 +/- 0.002 min-1, respectively; p greater than 0.4). The total area under the insulin curve during glucose tolerance tests was also similar in the clipped and sham groups (926 +/- 95 versus 869 +/- 126 microunits/ml x min; p greater than 0.4). There was no significant relation between systolic blood pressure and insulin area during glucose tolerance tests in the clipped group, but there was a positive rectilinear relation in the control group (r = 0.66; p = 0.01). Fourteen animals had euglycemic clamps 2 months after glucose tolerance tests. At that time, systolic pressure (direct femoral measurement) was higher in the seven clipped animals (189 +/- 13 mm Hg versus 122 +/- 5 mm Hg in controls; p less than 0.001). Insulin infusions of 1 and 4 milliunits/min/kg body wt effected similar plasma insulin levels in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1889850 TI - American Heart Association Prevention Conference II--Hypertension. Washington, D.C., April 24-26, 1990. Proceedings. PMID- 1889849 TI - Inhibition of endopeptidase-24.15 decreases blood pressure in normotensive rats. AB - The potent vasodilatory peptide bradykinin is cleaved at the Phe5-Ser6 bond in vitro by the metalloenzyme endopeptidase-24.15 (E.C.3.4.24.15). We now report that intravenous infusion of N-[1-(R,S)-carboxy-3-phenylpropyl]-Ala-Ala-Phe-p aminobenzoate, a specific active site-directed inhibitor of endopeptidase-24.15, produces an immediate drop in mean arterial pressure of as much as 50 mm Hg in pentobarbital-anesthetized, normotensive rats. Arterial pressure recovers within 5 minutes. The B2 bradykinin antagonist [Arg0,Hyp3,Thi5,8,D-Phe7]-bradykinin attenuates the decrease in mean arterial pressure resulting from treatment with the inhibitor. The endopeptidase-24.15 inhibitor potentiates the hypotensive effect of intravenous bradykinin infusion, increasing the maximal effect of the peptide by 47% and increasing the potency by almost 10-fold, while the response to intra-arterial bradykinin is less affected by the inhibitor. These results support a role for endopeptidase-24.15 in the inactivation of endogenous and exogenous bradykinin and suggest a direct involvement of the enzyme in the control of blood pressure. PMID- 1889851 TI - Insulin resistance and hypertension. AB - While clinicians have long recognized the apparent increased prevalence of hypertension among diabetics, sophisticated epidemiological analyses begun in the early 1970s have established that hypertensive individuals are more prone to hyperinsulinemia and glucose intolerance than normotensive individuals. Subsequently, the several hypertensinogenic effects of insulin were carefully studied in a number of laboratories. Most recently, the association of these two relatively common cardiovascular risk factors, hypertension and insulin resistance, was broadened to include lipid abnormalities, namely, increased concentrations of very low density lipoprotein triglycerides and decreased concentrations of high density lipoprotein cholesterol. These abnormalities, all of which appear in association more commonly than would be expected by chance, clearly predispose affected individuals to increased cardiovascular risk. This review summarizes our current understanding of the mechanisms underlying the relations between insulin resistance and hypertension and focuses discussion on the role of insulin as a common link between them. It concludes with recommendations, based on today's knowledge, for behavioral and therapeutic interventions aimed at the prevention of increased cardiovascular risk. PMID- 1889852 TI - Nutrition and hypertension prevention. AB - Hypertension has been related to both obesity and a high salt intake. Evidence for the associations of blood pressure with body weight and dietary salt intake is summarized. In both adolescents and adults correlations between blood pressure and weight are highly significant, and in longitudinal studies change in blood pressure over time is correlated with change in weight. Correlations between salt intake and blood pressure are less striking, and the results of trials of modest salt restriction demonstrate a small but significant effect on blood pressure. Individuals vary in their susceptibility to salt, and hypertensive individuals are more responsive than normotensive individuals. Dietary deficiencies of potassium and calcium may amplify the effect of a high salt intake on blood pressure. Animal models provide compelling evidence for a genetic component to salt sensitivity of blood pressure. In two hypertension prevention trials, change in blood pressure was more convincingly related to change in weight than to change in dietary salt. Avoidance of obesity, or weight reduction in overweight individuals, should be key strategies for hypertension prevention. Avoidance of salt excess is also appropriate, although currently available trial data do not justify a recommendation of rigorous salt restriction for the entire population. PMID- 1889853 TI - Can renal failure due to hypertension be prevented? PMID- 1889854 TI - Long-term effectiveness of nonpharmacological treatment of hypertension. AB - Various nonpharmacological therapies reduce the blood pressure of a significant portion of both patients with established hypertension and people who are considered to be at high risk for the development of hypertension; that is, they are secondary and primary preventions. Of the various therapies, weight reduction, sodium restriction, moderation of alcohol intake, and regular aerobic exercise have been shown to be most effective, whereas the effectiveness of other practices has been less uniform or smaller in degree. Changes in lifestyle, mainly involving diet and physical activity, should be widely used to treat and, hopefully, to prevent hypertension. PMID- 1889855 TI - Dissecting the primary causes of genetic hypertension in rats. AB - Blood pressure has a genetic component influenced by several to many genetic loci in both humans and animals; that is, blood pressure is a polygenic trait. Ultimately, the primary causes of genetic hypertension can only be established with genetic techniques. The primary tools for this analysis in animals are inbred strains of rodents selectively bred for differences in blood pressure and the genetic analysis of these strains by cosegregation techniques. This analysis determines whether it is possible to separate specific alleles at a candidate genetic locus from a component of blood pressure in genetically segregating populations. If the candidate alleles cosegregate with a component of blood pressure, these alleles must be the cause of the blood pressure differences or be linked on the same chromosome to alleles at other loci that cause blood pressure differences. If, on the other hand, the candidate alleles do not cosegregate with blood pressure, they cannot be the cause of the blood pressure differences. This analysis is straightforward in the case of a single-locus Mendelian candidate trait but is less informative if a candidate trait is itself polygenic. In this case, genetic analysis yields either 1) results that are compatible with, but not definitive proof for, a genetic role of the trait in causing blood pressure differences or 2) results that eliminate the trait as a cause of genetic differences in blood pressure. A complete listing of all the traits that have undergone genetic cosegregation analysis in rodents is given. PMID- 1889856 TI - Are there interactions and relations between genetic and environmental factors predisposing to high blood pressure? AB - An overview of published observations suggests that both genetic predisposition and environment work together to produce hypertension in most persons. High blood pressure before age 55 occurs 3.8 times more often among persons with a strong positive family history of high blood pressure. Much of the total variability in blood pressure in modern populations seems attributable to genetic factors. Estimates of the proportion of the variance attributable to all genetic factors (heritability [H2]) vary from 25% in pedigree studies to 65% in twin studies for sitting diastolic blood pressure. Several biochemical traits associated with high blood pressure are highly genetic (H2, 78-84%) and may help elucidate the pathophysiology of high blood pressure. While pertinent environmental factors such as salt intake, alcohol use, and amount of exercise also correlate significantly among relatives, only 7% of the total variance of diastolic blood pressure seems attributable to all shared environmental factors in family households. Thus most familial aggregation of high blood pressure appears to be due to genes rather than shared family environment. Practical benefit may result from identifying familial predisposition in multiple siblings with high blood pressure before age 55 and lipid abnormalities (labeled "familial dyslipidemic hypertension"). About 12% of high blood pressure patients have familial dyslipidemic hypertension and also have high risk of early coronary heart disease. Hyperinsulinemia and central obesity as well as high triglycerides and low high density lipoprotein cholesterol are prominent features of familial dyslipidemic hypertension.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1889857 TI - Do primary dysfunctions in neural control of arterial pressure contribute to hypertension? AB - This article is a summary of the physiological and clinical evidence that links the cause of essential hypertension to the brain. We stress the potential importance of a biochemical disturbance in the central role of angiotensin II in the regulation of arterial pressure. While the evidence is compelling, we acknowledge the need for further complete studies on this timely subject. PMID- 1889858 TI - Are vascular abnormalities a primary cause or secondary consequence of hypertension? AB - This paper reviews the evidence that the resistance vasculature is altered in hypertension and the role that the vasculature may play in the pathogenesis of the disease. Although functional changes (i.e., increased vascular smooth muscle sensitivity) have been found to be associated with some models of hypertension (e.g., spontaneously hypertensive rat), in human essential hypertension it appears that the abnormalities that predominate in the resistance vasculature are structural in nature. These changes result in an increased media/lumen ratio of the more proximal resistance vessels (i.d. 100-300 microns), and the changes are such that they could account for many of the altered hemodynamic characteristics seen in patients with essential hypertension (e.g., increased minimum vascular resistance, increased pressor response). However, evidence that the abnormal structure of the peripheral vasculature is a prime determinant of blood pressure is still lacking, and much of the available evidence suggests that the altered structure is a secondary adaptation. Nevertheless, the abnormal vascular structure may play an important pathological role concerning the morbid consequences of the hypertensive disease, suggesting that normalization of vascular structure is a desirable aim for antihypertensive treatment. At present it seems that treatment must be continued for long periods, maybe many years, before vascular structure is normalized. PMID- 1889859 TI - Local hormonal factors (intracrine, autocrine, and paracrine) in hypertension. AB - Vasoactive hormones acting as endocrine, neuroendocrine, or local hormonal systems (intracrine, autocrine, and paracrine) are an important component of the many factors that regulate blood pressure. Hypertension may be the result of an alteration in the balance between vasodepressor and vasopressor hormonal systems. Changes in this balance could be due to genetic factors such as mutations in one of the genes of the vasoactive system or environmental factors that alter the synthesis and release of one or more vasoactive hormones. Endocrine and neuroendocrine vasopressor hormonal systems, such as the renin-angiotensin system and catecholamines, play a well-established and important role in the regulation of blood pressure and the pathogenesis of some secondary forms of hypertension. The blockade of such systems has already resulted in effective antihypertensive treatment. The role of local hormonal systems is less well established; however, recent evidence suggests they also play an important role in the regulation of blood pressure and the pathogenesis of hypertension. Some vasopressor hormonal systems, such as the renin-angiotensin system, can act as both endocrine or local hormonal systems. Work using transgenic rats harboring the mouse Ren-2 gene has conclusively demonstrated that the renin-angiotensin system, acting as a local hormonal system, has the capability to cause severe hypertension. Whether this model of experimental hypertension mimics any type of human hypertension is not known. Vasodepressor hormones such as kinins, prostaglandins, and endothelium derived relaxing factor (EDRF) act mainly as local hormonal systems, with the notable exception of atrial natriuretic factor, which may act as both an endocrine and a local hormone. The tissue kallikrein-kinin system, acting either directly or via paracrine eicosanoids or EDRF, participates in local regulation of the circulation, renal function, and the acute antihypertensive effect of angiotensin converting enzyme inhibitors. A restriction fragment length polymorphism (RFLP) that distinguishes the kallikrein gene family of a strain of spontaneously hypertensive rats (SHR) from normotensive Brown Norway rats has been identified. In a set of 32 recombinant inbred strains derived from these SHR and Brown Norway strains, the RFLP marking the kallikrein gene family of SHR cosegregated with an increase in blood pressure. Also, in a study of Utah families it was found that a dominant-allele kallikrein gene expressed as high urinary kallikrein excretion was associated with a decreased risk of essential hypertension. In conclusion, vasopressor and vasodepressor hormones, acting not only as endocrine but also as local hormones, play an important role in the regulation of blood pressure and the pathogenesis of hypertension.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1889860 TI - Childhood predictors of future blood pressure. AB - Blood pressure in infants and children is much lower than that in adults. It is suspected that children whose blood pressures are greatest for their age or body size may be destined for future hypertension. However, it is apparent that some children with lower blood pressures are also destined for hypertension as adults. Children with a family history of hypertension demonstrate greater blood pressure and heart rate responses to mental challenge. These responses are enhanced when a high salt diet is consumed. Increased maximal exercise systolic blood pressure and increased left ventricular wall mass in childhood add significantly to the prediction of future high blood pressure. In addition, the acquisition of excess weight for height from childhood to young adult life adds to the prediction of future blood pressure elevations. Both children and adults who are obese have significantly higher blood pressures than those who are lean. Approximately 34% of the variability in body mass index is explained by genotype differences at a single recessive locus, 41% by genotype differences at polygenic loci, and 25% by nongenetic factors. Thus, the genetic influence of obesity may be an important factor responsible for elevated blood pressure in both children and adults. PMID- 1889861 TI - Can essential hypertension be subclassified with respect to mechanism? AB - Hypertension may result from a variety of abnormalities. The rise in blood pressure may trigger other secondary events that further influence cardiovascular homeostasis. The ability to measure some markers associated with hypertension or the responsiveness of blood pressure to nutritional interventions or to specific therapeutic agents may also have pathogenetic implications. The ultimate goal of further knowledge in this area should be to understand the fundamental abnormalities responsible for hypertension. Such insight would permit more effective treatment and, perhaps, primary prevention of this ubiquitous and multifaceted disorder. PMID- 1889862 TI - Blood pressure and high blood pressure. Aspects of risk. AB - This report deals with three aspects of risk related to blood pressure and high blood pressure. The first aspect of risk concerns distributions of systolic blood pressure (SBP) and diastolic blood pressure (DBP) in the adult population and their relation to long-term risk of morbidity and mortality. By middle age, only a minority (about 20%) of Americans have optimal SBP and DBP levels, less than 120 mm Hg and less than 80 mm Hg, respectively. For the majority with higher levels, risks of major clinical events, including death from cardiovascular diseases and from all causes, are markedly increased. The relations of SBP and DBP with risk are strong, continuous, and graded. Risk is sizable not only for persons with high blood pressure by usual clinical criteria (SBP greater than or equal to 140 mm Hg or DBP greater than or equal to 90 mm Hg), but also for those with "high-normal" blood pressure (e.g., SBP 130-139 mm Hg or DBP 80-89 mm Hg). Thus, the blood pressure problem is a population-wide one and requires for its control a combined population-wide and high-risk strategy. A major component of this strategy must be nutritional-hygienic measures for the primary prevention of the rise in blood pressure during adulthood and of high blood pressure (i.e., primary prevention not only of the complications of high blood pressure but also of high blood pressure itself) through improved lifestyles having the potential to shift downward the blood pressure distribution of the whole population. The second aspect of risk concerns the known risk factors (i.e., aspects of modern lifestyle) leading to the mass occurrence of blood pressure rise during adulthood and of high blood pressure. These risk factors are high salt intake, high dietary sodium/potassium ratio, calorie imbalance and resultant obesity, and high alcohol intake. The extensive data base establishing the role of these common traits in the etiology of the blood pressure/high blood pressure problem is the scientific foundation for efforts to achieve the primary prevention of high blood pressure. The third aspect of risk relates to the combined impact of other risk factors along with blood pressure-high blood pressure in markedly increasing the probabilities of morbidity and mortality (e.g., "rich" diet, diet-dependent serum cholesterol and uric acid, smoking, diabetes, and target-organ damage). Prevention and control of lifestyle-related traits are essential components of the strategy for dealing with the blood pressure-high blood pressure problem. PMID- 1889863 TI - Antibiotic usage for initial empirical treatment of infections in hospitalized patients in West Germany. AB - Antibiotic usage for initial empirical treatment of infections in hospitalized patients was assessed by means of a questionnaire sent to physicians in charge of surgical and medical intensive care units, departments of neurosurgery, neurology, general surgery, thoracic surgery, internal medicine and pediatrics. Analysis of a total of 82 questionnaires filled in by the various departments revealed that the most frequently used regimens for initial empirical therapy were combinations of a broad spectrum penicillin with an amino-glycoside or of a second generation cephalosporin with an aminoglycoside in intensive care. Third generation cephalosporins ranked third among combination partners with aminoglycosides. Imipenem and fluoroquinolones were used only rarely for first line treatment. Second line treatment was most frequently with third generation cephalosporins or imipenem/cilastatin for internal wards and intensive care with an extension for staphylococcal infections with vancomycin or teicoplanin as the most frequent additional antibiotics. Patterns of antibiotic usage changed with regard to infection sites with a predominance of third generation cephalosporins or broad spectrum penicillins in combination with an aminoglycoside and metronidazole in abdominal sepsis and peritonitis. In case of pneumonia a differentiation between community acquired and hospital acquired pneumonias was made. Treatment was predominantly carried out with penicillin G, ampicillin or a second generation cephalosporin with or without the addition of an aminoglycoside in case of community acquired pneumonia. The addition of clindamycin or metronidazole was considered for suspected staphylococcal infection or aspiration pneumonia. Third generation cephalosporins were preferred for pneumonia treatment in surgical patients. PMID- 1889864 TI - The need for intubation in serious upper respiratory tract infection in pediatric patients (a retrospective study). AB - Serious bacterial infections occurred in ten children (1.4%) of 710 patients with croup admitted to the Soroka Medical Center during the years 1983-1989. Sixty four patients (9% of all croup patients) were admitted to the pediatric intensive care unit (PICU), and 13 of them (20%) required intubation. Bacterial infections were noted in nine of the 13 intubated patients, in none of the other 51 PICU patients who did not require intubation and in one of the 646 patients (0.2%) who were not admitted to the PICU (p less than 0.0001). There was no difference in age, ethnic origin, or body temperature on arrival between the two PICU groups. Causative microorganisms were isolated from blood samples (three cases) and tracheal pus (eight cases). All intubated PICU patients were seriously ill: eight had bacterial tracheitis and one supraglottitis. Patients with bacterial tracheitis required frequent suctioning of the trachea for copious purulent secretions. The single patient with bacterial infection who was not admitted to the PICU had transient bacteremia. We conclude that the need for intubation in croup patients was an indicator for the presence of a serious bacterial infection. PMID- 1889865 TI - Perinatal transmission of Chlamydia trachomatis. The use of serological tests in detecting infected women. AB - A study is presented on the use of serological tests for the detection of Chlamydia trachomatis in 273 pregnant women. 166 were cultured for C. trachomatis and nine (5.4%) were positive. Three culture-positive babies, all born to culture positive women, had conjunctivitis. Elevated IgG and IgA antibody levels were seen in six (67%) and three (33%) of the infected women, respectively. Three (2.4%) of IgG antibody-negative mothers (n = 126) were positive by culture. Compared to serology culture of the microorganism appears as the most reliable way of detecting infected women. PMID- 1889866 TI - Neonatal sepsis in an intensive care unit and results of treatment. AB - Incidence and fatality of neonatal sepsis in intensive care units have been relatively high despite progress in the management of very ill neonates and combined treatment of sepsis with antibiotics. Between 1985 and 1989 944 children (632 premature babies and 312 term babies) were treated in the intensive care unit of the University Children's Hospital of Kiel. The incidence of sepsis was 5% (congenital sepsis 4%, sepsis acquired after birth 1%). Pneumonia occurred in 4% (congenital pneumonia in 2%, postnatal pneumonia in 2%). Early diagnosis and treatment with piperacillin plus cefotaxime reduced the mortality rate of sepsis to 2%. Sepsis never developed under treatment with piperacillin plus cefotaxime. Early recognition of neonatal sepsis by a good blood culture technique and beginning of treatment on first suspicion of sepsis with cefotaxime and piperacillin can improve the results especially in intensive care patients. PMID- 1889867 TI - Interleukin-1 secretion by blood monocytes of septic premature infants. AB - This study examined lipopolysaccharide (LPS) induced in vitro secretion of interleukin-1 (IL-1) by peripheral blood monocytes from pre-term infants with and without sepsis. Thirteen pre-term babies were tested; eight were completely healthy and five suffered from six episodes of sepsis. The latter group was tested both in the acute septic phase and in the convalescent period. IL-1 secretion by monocytes derived from septic pre-term infants was lower, but not significantly different from healthy pre-term infants (7.1 +/- 1.0 U/ml versus 8.1 +/- 0.9 U/ml, respectively). IL-1 secretion by monocytes of eight control full-term babies was in the same range (8.4 +/- 0.6 U/ml). In the convalescent period IL-1 secretion by monocytes from septic pre-term babies increased (9.0 +/- 0.3 U/ml) and was significantly higher than values measured during acute infection (p less than 0.05). Septic premature babies were also found to have higher absolute blood neutrophil concentration (p less than 0.001), but their body temperature did not increase along the infectious stage. The decreased secretion of IL-1 by monocytes from pre-term babies in the acute phase of infection compared to the convalescent period may have contributed to their inability to mount appropriate immunological as well as inflammatory responses. Sepsis promoting IL-1 production in vivo may have limited the monocytes' capacity for LPS stimulated IL-1 synthesis in vitro. PMID- 1889868 TI - Interaction between HDV and HBV infection in HBsAg-chronic carriers. AB - We studied the interaction between HBV and HDV infection in 149 consecutive subjects with HBsAg positive chronic hepatitis and in 22 chronic HBsAg healthy carriers. Liver HBcAg was detected in 52 (30.4%) of the 171 subjects. Of these 52, 35 were HBV-DNA and HBeAg positive, 11 HBV-DNA positive only; two HBeAg positive only and four were negative for both HBeAg and HBV-DNA. None of the 119 HBcAg-negative subjects had detectable HBV-DNA in serum. HD-Ag in hepatocytes was detected in 31 of the 171 subjects (18%); it was detectable in none of the 22 HBsAg healthy carriers, in four of the 56 patients with chronic persistent hepatitis (7.2%), in six of the 24 patients with chronic lobular hepatitis (25%), in 16 of the 40 patients with chronic active hepatitis (40%) and in five of the 29 with cirrhosis (17%). A presence of anti-HD in serum in the absence of liver HD-Ag was found in 54 of the 171 subjects (32%). This condition was observed not only in patients with a progressive disease (37.7% of chronic active hepatitis or cirrhosis and 33% of chronic lobular hepatitis), but also in healthy carriers (36%) and in chronic persistent hepatitis patients (21.4%). Liver HBcAg was detected in 6.4% of the 31 HD-Ag-positive patients, in 12.9% of the 54 HD-Ag negative/anti-HD positive, but in 50% of the 86 with no marker of HDV infection. HDV appears to inhibit HBV genome and such inhibition may persist even when anti HD is the only HDV marker detectable. PMID- 1889869 TI - An outbreak of molluscum contagiosum in a kibbutz. AB - Molluscum contagiosum is a viral disease that presents in a primary care setting as single or multiple wart-like lesions. We have seen an outbreak of Molluscum contagiosum in a small rural community, affecting 34 individuals. The most infected were children two-to nine-years-old. The diagnosis was made on clinical grounds. Spread appeared to be as a result of direct contact and by fomites. There was no evidence, in our study, of spread via swimming pool. Cryosurgery was used to treat our patients with Molluscum contagiosum. PMID- 1889870 TI - Isolation of Chlamydia trachomatis from prostatic tissue of patients undergoing transurethral prostatectomy. AB - Chlamydia trachomatis was isolated from three of 100 prostatic tissue specimens obtained from patients undergoing transurethral resection of the prostate. All examined patients were free from symptoms of urethral or prostatic inflammation. Our findings are in accordance with the high incidence of asymptomatic chlamydial infection of the lower genital tract and the increasing evidence that C. trachomatis can cause infection of the prostate. PMID- 1889871 TI - Characterization of 20 Entamoeba histolytica strains isolated from patients with HIV infection. AB - Twenty Entamoeba histolytica strains from patients with HIV-1 infection were isolated and compared with E. histolytica strains from patients without HIV infection. The isoenzyme pattern of the hexokinase as well as the hybridization with known DNA-probes were used as markers for pathogenicity. According to these markers, all 20 strains could be regarded as being nonpathogenic. Direct measurements of the virulence were carried out: destruction of monolayer tissue culture cells, capacity of phagocytosis and the ability to induce liver abscesses in the hamster. The virulence of strains from HIV patients was comparable to that of E. histolytica strains which had been isolated from HIV-negative asymptomatic carriers. In agreement with this, none of the HIV-positive patients showed symptoms of an invasive amebiasis. By PRC, no HIV-1 proviral DNA could be evidenced in the E. histolytica strains which had been isolated from HIV patients. PMID- 1889872 TI - Resistance to trimethoprim in Haemophilus influenzae. AB - The mechanisms of resistance to trimethoprim in eleven U.K. clinical isolates of Haemophilus influenzae were studied. The levels of dihydrofolate reductase (DHFR) activities in crude extracts from four resistant wild-types were similar to those in susceptible controls. However, activities in extracts from the other seven resistant wild-type isolates, and transformants of two of these, were at least triple those in the sensitive strains. Resistance to trimethoprim was also selected for in vitro during prolonged exposure to the drug and was associated with increased levels of DHFR specific activity in the mutants. DHFR enzymes were, however, still very susceptible to inhibition by trimethoprim. Activities in four extracts, including one from a transformant of a resistant mutant, were reduced by at least 45% following incubation with 10(-8) M trimethoprim. The results suggested that overproduction of the chromosomal DHFR enzyme may be the resistance mechanism in some organisms. The much lower DHFR activities measured in extracts from other resistant isolates may reflect synthesis of chromosomal enzymes that have reduced susceptibility to trimethoprim. PMID- 1889873 TI - Flucytosine conversion to fluorouracil in humans: does a correlation with gut flora status exist? A report of two cases using fluorine-19 magnetic resonance spectroscopy. AB - A relationship between the gut flora level, particularly gram-negative enterobacilli, and the in vivo flucytosine conversion to fluorouracil has been observed in humans from the fluorine-19 magnetic resonance spectroscopy analysis of urine from two patients treated with the flucytosine- (6 to 9 g/day) amphotericin B (1 mg/kg/day) combination. Indeed the percentage of fluorouracil metabolites was extremely low (less than 0.6% of total fluorinated compounds excreted) when the number of enterobacillary colonies was low (less than 10(3] and higher (3.5 to 8.8%) when enterobacillary colonies were under reconstitution or in the normal range (10(5) to 10(8]. The intestinal microflora assessment may therefore be of high interest to predict the risk of an additive flucytosine induced myelotoxicity suspected to be due to fluorouracil during flucytosine chronic therapy. PMID- 1889875 TI - Haemophagocytic visceral kala azar. PMID- 1889876 TI - Pathogenicity of Blastocystis hominis. PMID- 1889874 TI - Treatment of a meningitis due to an Enterobacter aerogenes producing a derepressed cephalosporinase and a Klebsiella pneumoniae producing an extended spectrum beta-lactamase. AB - A case of nosocomial meningitis due to a Klebsiella pneumoniae producing a CAZ-5 extended-spectrum beta-lactamase and an Enterobacter aerogenes producing a derepressed cephalosporinase is reported. The intrathecal catheter incriminated was removed and a treatment with ceftazidime (4 g/24 h) and amikacin (1.5 g/24 h) was started. After 24 h ceftazidime was replaced by imipenem (2 then 4 g/24 h). This treatment failed to obtain cerebrospinal fluid sterilization; therefore the imipenem dosage was increased to 8 g/24 h and two intrathecal infusions of amikacin (50 mg) were carried out. Thereafter the patient recovered. PMID- 1889878 TI - The combined effects of noise, nightwork and meals on mood. AB - The present paper describes a laboratory study on the acute effects of a combination of noise and nightwork on subjective mood. Subjects tested in the presence of noise felt more alert than those tested under quiet conditions. Circadian variation in alertness was also reported, but the noise did not change the shape of the alertness rhythms. The only exception to this was found after the mid-shift meal. Subjects tested under quiet conditions felt less alert after the meal than before it, whereas those tested in the presence of noise reported that they were more alert in the post-meal period. These results suggest that noise and nightwork produce independent effects, whereas noise and meals influence similar mechanisms. PMID- 1889877 TI - Combination effect of SCE-2787 and cefepime with aminoglycosides on nosocomial gram-negative bacteria. AB - The in vitro activity of cefepime and SCE-2787, two new parenteral cephalosporins, and the combination effect with tobramycin and gentamicin against nosocomial gram-negative rods was studied using checkerboard agar dilution technique. Cefepime showed excellent in-vitro activity against Klebsiella pneumoniae, Enterobacter cloacae, Serratia marcescens and Proteus vulgaris (MIC90 0.03-0.125 mg/l) and good to moderate activity against Acinetobacter anitratus, Pseudomonas aeruginosa and Pseudomonas cepacia (MIC90 4-16 mg/l). SCE-2787 had an excellent activity against Citrobacter spp. (MIC90 0.125 mg/l) and a very good activity against A. anitratus, P. aeruginosa and P. vulgaris (MIC90 1-2 mg/l). Pseudomonas maltophilia was not inhibited at therapeutically achievable concentrations (MIC90 64 mg/l). On average, 14-28% of the strains were inhibited by synergistic SCE-2787 aminoglycoside-combinations, whereas only 8.6% were inhibited by a synergistic effect of the combination with cefepime and gentamicin. No antagonism occurred with any of the combinations. PMID- 1889879 TI - Central nervous system effects and visual fatigue in VDT workers. AB - To assess central nervous system effects and visual fatigue induced by work with visual display terminals (VDT), symptom frequency was assessed and visual evoked potential (VEP), critical flicker fusion (CFF) and near-point distance were measured in 24 female keypunchers before and after 2.5 h of VDT work and in 6 non VDT-exposed subjects at the same intervals. Each keypuncher had been engaged in data entry for 1-7 (mean, 4) years. After VDT work, the number of complaints of subjective fatigue as well as an objective measure of near-point distance were significantly increased as compared with those before work; also, the N75, P100 and N145 latencies of VEP were significantly prolonged. The change of P100 latency during VDT work was inversely correlated with the number of years worked in data entry. No significant change was seen in any of these tests in the non VDT-exposed subjects. The changes in N75 latency and subjective fatigue related to drowsiness and dullness in the keypunchers were significantly larger than those in the non-VDT-exposed subjects. The CFF was significantly lower in keypunchers than in non-VDT-exposed subjects in both the first and the second tests. These data suggest that VDT work is associated with impairment of the visual nervous system function, that VEP latencies appear to be a sensitive indicator of visual fatigue, at least transiently, and that CFF appears to be a good parameter for estimations of chronic visual fatigue. PMID- 1889881 TI - Quantitation of urinary chlorobenzene metabolites by HPLC: concentrations of 4 chlorocatechol and chlorophenols in urine and of chlorobenzene in biological specimens of subjects exposed to chlorobenzene. AB - A simple method for the determination of 4-chlorocatechol (ClCh, 4-chloro-1,2 benzenediol) and chlorophenols (ClPh), metabolites of monochlorobenzene (ClBz), in urine by high performance liquid chromatography (HPLC) is described. Enzymatic hydrolysates of urine were applied to a stainless-steel column packed with octadecyl-silanized silica gel, and a mixed solution of 20 mM potassium phosphate monobasic: acetonitryl (75:25, v/v) was used as a mobile phase. The procedures for ether extraction and evaporation of extract could be omitted. The accuracy and precision of the present HPLC method were satisfactory. The excretion kinetics of ClCh and p-ClPh were investigated over 35 h after cessation of ClBz inhalation. Proportional relationships between concentrations of ClBz in air and of its metabolites in urine were observed. The slopes of regression lines predicting the levels of ClCh, p-ClPh and total ClPh in urine taken during the last 2 h of exposure to ClBz in air were 6.56, 1.13 and 2.83 mg/g creatinine for 1 ppm ClBz, respectively. ClBz in the blood and the end exhaled air of subjects at the end of exposure were identified by gas chromatography (GC) and mass spectrometry. A proportional relationship was observed between the concentration of ClBz in air and that in blood. The validity of the threshold limit value (TLV) for ClBz as evaluated from the subjective and objective symptoms is discussed. PMID- 1889880 TI - Investigations of the frequency of DNA strand breakage and cross-linking and of sister chromatid exchange in the lymphocytes of electric welders exposed to chromium- and nickel-containing fumes. AB - A total of 39 electric welders exposed to chromium and nickel were compared with 18 controls standardized for age, smoking habits and sex with respect to the frequency of sister chromatid exchange (SCE) and of DNA strand breakage and cross linking (measured by the method of alkaline filter elution) in their blood lymphocytes. A significant correlation was found between the frequency of SCE and of individual DNA strand breakage and the concentration of chromium in the urine. Less DNA from the welders than from the control group was eluted through the two filter types used (polycarbonate and polyvinylidene fluoride filters). This must be interpreted as resulting from the presence of DNA-protein cross-links, which has the secondary effect of leading to a relative reduction in the measurable frequency of strand breakage amongst the welders. The present results are in good agreement with in vitro and in vivo investigations that confirm the importance of DNA-protein cross-links for the carcinogenic effect of chromium. PMID- 1889882 TI - Nutritional status and physical fitness of Polish miners and steel workers. AB - The nutritional status of 690 miners and 604 steel workers was determined. Their physical fitness was estimated by an indirect method using the Astrand Rhyming nomogram. The nutritional status parameters indicated an increase in weight in relation to increasing age: 57% of the subjects were overweight. Over 70% were current smokers. The mean value for V O2max was 2.8 +/- 0.5 l/min/38 +/- 7 ml/kg per min. The high percentage of subjects (Polish miners and steel workers) who eat too much, are overweight, smoke and who have a low physical-activity level during their leisure time demonstrates the risk for coronary heart disease. PMID- 1889883 TI - A physiologically based mathematical model for the human inhalation pharmacokinetics of 1,1,2-trichloro-1,2,2-trifluoroethane. AB - A physiologically based mathematical model is described for the human inhalation pharmacokinetics of 1,1,2-trichloro-1,2,2-trifluoroethane (FC113). Physiological parameters for the model are derived from the scientific literature. Partition coefficients are determined from in vitro measurements. Predictions of the resulting model for breath and blood concentrations compare well with results of a human volunteer study described in a companion paper (Woollen et al. 1990). Using this data some alternative models are also examined with different choices of physiological parameters and partition coefficients. The mathematical model is used to examine the consequences of metabolic elimination of FC113. A value for metabolic clearance is estimated using the during-exposure breath concentration data; however, the concentrations of FC113 in breath or blood during and after exposure are shown to be insensitive to metabolic clearance. Consequently, no firm conclusion can yet be drawn as to whether FC113 is metabolised by man. PMID- 1889884 TI - Respiratory nicotine absorption in non-smoking females during passive smoking. AB - The aim of this study was to measure nicotine concentrations in inspired and expired air so as to learn more about respiratory (nasopharyngeal cavity and lung) nicotine absorption from inspired air and to estimate the nicotine intake during passive smoking. A total of 17 young non-smoking women were exposed to experimental passive smoking. Inspired and expired air was sucked at a constant rate into samplers filled with acid-treated diatomite (Uniport-S) to absorb nicotine in the air. Absorbed nicotine was assayed by gas chromatography. The range of nicotine concentration in the inspired air was 40-200 micrograms/m3. In this setting, 47 samples obtained from the 17 subjects were assayed. Nicotine absorption, which was calculated as [(nicotine concentration in inspired air nicotine concentration in expired air)/nicotine concentration in inspired air] x 100, remained at 60%-80% (mean +/- SD, 71.3% +/- 10.2%) without being affected by the nicotine concentration in the inspired air. From this result, it was estimated that the average intake of nicotine was 0.026 mg/h in a group of non smokers exposed in a room containing a nicotine concentration of 100 micrograms/m3, which is equivalent to fairly severe involuntary tobacco smoking. This is the first report on the estimation of respiratory nicotine absorption and nicotine intake during passive smoking based on the direct measurement of nicotine concentrations in both inspired and expired air. PMID- 1889885 TI - Circulatory disturbances of the foot in vibration syndrome. AB - Circulatory disturbances of the foot in patients with vibration syndrome were studied by measuring the skin temperature of both index fingers and great toes through a 3-min immersion of the right foot in cold water at 10 degrees C. Subjects included 11 patients with vibration-induced white finger (VWF) [VWF(+) group], 12 patients without VWF [VWF(-) group], and 20 healthy referents not exposed to vibration. Patients were all male chain saw operators who had scarcely been exposed to vibration of the foot. The prevalence of coldness felt in the upper and lower extremities was greater than 90% in the VWF(+) group, about 60% in the VWF(-) group, and less than 10% in the referents. The extent of the coldness was greatest in the VWF(+) group. The skin temperature of both fingers and toes was lowest in the VWF(+) group, somewhat higher in the VWF(-) group, and highest in the referents both before and after immersion. These findings indicate that patients with vibration syndrome, especially those with VWF, have circulatory disturbances in the foot as well as in the hand. The disturbances in the foot may be related to long-term repeated vasoconstriction in the foot induced by hand-arm vibration through the sympathetic nervous system. PMID- 1889886 TI - The mutagenic activity and polycyclic aromatic hydrocarbon content of mineral oils. AB - Naphthenic distillates (raw or acid-treated) and motor and emulsifiable aluminium rolling oils were tested for mutagenicity in the Salmonella/microsome assay using the TA98 and TA100 strains. The polycyclic aromatic hydrocarbon (PAH) content of oil samples was also determined in parallel. In the presence of metabolic activation, both untreated and acid-treated naphthenic distillates were found to be mutagenic on a modified Ames test. One untreated sample showed the highest value of mutagenic potency (50 net revertants/mg oil for strain TA98). The PAH content of naphthenic distillates was about 10% (w/w) and was slightly reduced by sulfuric acid/earth treatment (1%). Non-mutagenic paraffin- and solvent-extracted crankcase oils became active, both with and without enzyme activation, after long use as gasoline engine lubricants, whereby their PAH content doubled (from 1.5% to 3%, w/w). A refined emulsifiable mineral oil also became directly mutagenic in both Salmonella strains after prolonged use in an aluminium hot-rolling mill. As the PAH levels found in used rolling oils was very low, we cannot explain their mutagenic activity. Mutagenicity was greatly reduced following careful cleaning of the oil bath and of the entire rolling machine. The present data reveal both the potential risk of occupational exposure to unrefined or mildly treated oils and the formation of mutagens in highly refined oils if the latter are used at high temperatures. The formation of mutagens in oils used in the metal-working industry can be prevented by careful industrial hygiene measures. PMID- 1889887 TI - An inverse lead air to lead blood relation: the impact of air-stream helmets. AB - At a secondary smelter (24 smelting workers, 13 refinery workers), data on exposure to lead were collected by systematic observation of hygienic behaviour, a questionnaire, personal sampling of lead dust in ambient air (PbA) and determination of lead in the blood level (PbB). The smelting workers showed a negative relation between PbA and PbB. The 53% variance in PbB levels in the smelting workers can be explained by the combination of PbA, the percentage of time an air-stream helmet is worn, the frequency of cigarette smoking at the workplace and the amount of spitting. Air-stream helmets and spitting contribute to a lower PbB, whereas smoking contributes to a higher PbB. Moreover, expected PbB levels were computed by using several regression equations for the relation between PbA and PbB, as suggested in the Final OSHA Standard for Occupational Exposure to Lead (OSHA 1978). As the percentage of time an air-stream helmet is worn increases, the deviation from the expected PbB falls substantially. The refinery workers showed the expected weak positive correlation coefficient between PbA and PbB. No direct relation between the PbB level and the observed hygienic behaviour could be established. However, there was a positive relation between the level of education and the level of PbB. Moreover, the level of education was related to the frequency of eating at the workplace and negative as far as the percentage of time gloves are worn is concerned. Our conclusion is that hygienic behaviour is a major factor that modifies the relation between PbA and PbB in groups of workers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1889890 TI - The French registry for plasma exchange: a four year experience. PMID- 1889889 TI - Cardiac support and mechanical cardiac replacement. PMID- 1889888 TI - Failure to find a relationship between mnestic skills of octogenarians and aluminum in drinking water. AB - High concentrations of aluminum (greater than 80 micrograms/l) in drinking water have been related to an elevated incidence of Alzheimer's disease. Mnestic and naming skills of residents living for greater than 15 years in districts with high (98 micrograms/l) or low (4 micrograms/l) aluminum concentrations [Al] in the drinking water were evaluated in a population survey by examining 800 residents aged 81 to 85 using the mnestic subtest of the Mini Mental Status test (Zurich variant). The mnestic and naming performance of the octogenarians did not differ between the high- and low-content-areas. Since 73% of dementias are at least partly caused by Alzheimer's disease in the area examined and because the short test used discriminates demented from healthy octagenarians as well as tests involving extensive examinations, the findings of this study suggest with a high probability that the [Al] of drinking water is not an essential factor in the pathogenesis of senile dementia. The serum [Al] the urinary [Al] and the urinary [Al]/creatinine ratio were measured twice in ten clinically diagnosed Alzheimer patients and ten controls in both areas. No significant difference was found, which confirms the negative epidemiological findings. PMID- 1889891 TI - Bioartificial pancreas and liver: a review. PMID- 1889892 TI - Combined recombinant human erythropoietin-blood letting strategy for treating anemia and iron overload in hemodialysis patients. AB - We studied the feasibility of treating refractory anemia and post-transfusional serious hemochromatosis in a patient undergoing hemodialysis (3x4 h weekly) for fourteen years, with recombinant human erythropoietin (r-HuEPO) associated with blood-letting. Blood transfusion previously received by the patient at a rate of two units of packed red cells every month for nine years was stopped and r-HuEPO (80 U/kg b.w.) was administered i.v. at the end of each hemodialysis. When Hct increased over 30%, approximately 40 ml of blood was removed per hemodialysis session in an attempt to accelerate iron loss. Excellent control of anemia and hemochromatosis was achieved after seven months of treatment. The patient's general condition and skin pigmentation were significantly improved. PMID- 1889893 TI - In vivo comparative evaluation of hemodialysis tubing plasticized with DEHP and TEHTM. AB - The migration of plasticizers from blood lines was studied in 11 patients with chronic renal failure on hemodialysis for a period of six months. Di-2 ethylhexylphthalate (DEHP), the conventional plasticizer, was compared with tri-2 ethylhexyltrimellitate (TEHTM). A liquid chromatography method for quantitative determination of DEHP and TEHTM in human blood plasma is described. During treatment with tubing containing DEHP, the plasma level of DEHP rose from 0.10 micrograms/ml (less than 0.05-0.17 n = 11) to 0.70 micrograms/ml (0.30-1.6 n = 11). When the patients were changed to tubing containing TEHTM, the concentration of DEHP was below or close to the detection limit and TEHTM could not be detected. No adverse events of either tubing were found as regards acute toxic effects, performance or applicability. PMID- 1889894 TI - Effects of recombinant human erythropoietin on the plasma levels of vasoactive regulatory peptides in patients on maintenance hemodialysis. AB - The plasma levels of nine vasoactive regulatory peptides were measured by radioimmunoassay in six stable patients with chronic renal failure on regular hemodialysis, before and during treatment with recombinant human erythropoietin (r-huEPO). All patients responded with significant increases in hemoglobin concentrations and hematocrit. Mean arterial blood pressure was not significantly changed nor were there any changes of body weight or interdialytic body weight gain. The mean plasma levels of atrial natriuretic peptide and motilin decreased significantly, by 38 and 16 percent respectively, during r-huEPO treatment. There were no changes in mean plasma levels of arginine vasopressin, calcitonin gene related peptide, beta-lipotropin, gamma 2-melanocyte-stimulating hormone, neuropeptide Y, substance P or vasoactive intestinal peptide. No significant correlations were observed between changes of plasma peptide levels and changes of mean arterial blood pressure. PMID- 1889895 TI - Effect of ethanol perfusion on creatinine removal in a Roux-Y intestinal segment. AB - Five rats and 2 goats had a bypass operation to allow infusion of sorbents through an inlet ostomy. The sorbents passed through one limb of intestine isolated from food contact to join a food limb which included 30-40% of the original length of small intestine. In goats, serum creatinine levels were elevated by infusion of sterile creatinine solutions intravenously. Twenty-four hour urines were collected before, during and after periods of infusion of sorbents into the inlet ostomy. Infusion of charcoal into the ostomy had little effect on the total daily urinary creatinine excretion (TDUC). However infusion of 4.3 g/kg/day ethanol decreased the TDUC significantly, in both species. In rats, 8.6 g/kg/day ethanol infusion had an even greater effect on TDUC. Studies of intraluminal creatinine concentration in the distal part of the sorbent segment indicated that especially when serum concentration of creatinine is over 2 mg%, ethanol greatly increases the intraluminal creatinine concentration in the intestine. It is concluded that ethanol, in combination with intestinal sorbents or alone, could allow intestinal dialysis to remove considerably more creatinine, and possibly aid transport of other organic substances. PMID- 1889896 TI - The measurement of blood density to investigate protein deposition at the blood/hollow fiber membrane interface during ultrafiltration. AB - Concentration polarization and secondary membrane formation change the membrane hydraulic permeability of capillary filters during hemofiltration reducing initial value filtration rates up to 50%. This leads to a significant loss of filter efficiency which must be taken into consideration when designing filters for long-term application such as in implantable artificial kidneys. By measuring blood density uninterrupted over a period of time using the mechanical oscillatory technique it is possible to follow the dynamics of protein deposition at the interface between the blood and capillary walls. The resulting picture of the deposition behaviour can lead to a better understanding of time-dependent filtration where flow and pressure conditions change. Protein deposition (Pt) with polysulfone membranes in relation to the effective capillary surface was in the range of 2.2. mg/(h x cm2) according to a logarithmic function (Pt = a + b x log(t)). PMID- 1889897 TI - Principle of operation, design criteria and fluid dynamics of a new bileaflet heart valve prosthesis. AB - Bileaflet heart valves show the best fluid dynamic behaviour among mechanical valves and, as a consequence, give the best clinical results. A new bileaflet heart valve has been designed whose main characteristics are the kind of leaflet movement, low profile, fluid dynamics and material. Two flat leaflets move freely inside a very low profile housing ring. The movement is described by the rolling without sliding of the leaflet surface around a cylindrical surface on the inner wall of the housing. The opening angle is 85 degrees. Both the leaflets and the housing are machined from a solid piece of titanium and then covered with carbon by ion beam techniques. The design phase and the first fluid dynamic evaluation were done by numerical methods. PMID- 1889898 TI - A new glucose clamp algorithm: clinical validation. AB - A new glucose clamp technique for in vivo studies of insulin sensitivity was validated clinically. Eighteen patients (10 males, 8 females, age 35-80 years, body mass index 34.6-17.04) were connected to a computer-assisted artificial pancreas "Betalike R", using a new algorithm based on a "minimal model", to carry out the glucose clamp technique automatically and especially to overcome the well known problems of its priming phase. We performed the euglycemic hyperinsulinemic clamp in four patients and the hyperglycemic hyperinsulinemic clamp in 14. In one patient both clamps were done. The mean priming time to reach steady-state glycemia was 20 min. Plasma insulin concentrations were measured every 20 min. This new automatic glucose clamp technique enables the priming phase to be run without any significant overshoot, and accidental variations of glycemia in steady state were reduced to a minimum. The system showed satisfactory safety and stability in controlling the patient's glycemia and assured high speed of the priming phase. PMID- 1889899 TI - Medical expert systems based on causal probabilistic networks. AB - Causal probabilistic networks (CPNs) offer new methods by which you can build medical expert systems that can handle all types of medical reasoning within a uniform conceptual framework. Based on the experience from a commercially available system and a couple of large prototype systems, it appears that CPNs are now an attractive alternative to other methods. A CPN is an intensional model of a domain, and it is therefore conceptually much closer to qualitative reasoning systems and to simulation systems than to rule-based or logic-based systems. Recent progress in Bayesian inference in networks has yielded computationally efficient methods. The inference method used follows the fundamental axioms of probability theory, and gives a sound framework for causal and diagnostic (deductive and abductive) reasoning under uncertainty. Experience with the prototypes indicates that it may be possible to use decision theory as a rational approach to test planning and therapy planning. The way in which knowledge is acquired and represented in CPNs makes it easy to express 'deep knowledge' for example in the form of physiological models, and the facilities for learning make it possible to make a smooth transition from expert opinion to statistics based on empirical data. PMID- 1889900 TI - The PRIST-2 development environment: architecture and implementation. AB - The PRIST-2 system has been designed as an interactive and high-productivity tool for the rapid prototyping and development of medical applications. Three major issues were addressed in this research project which derived from the evolution of a previous 4th generation software package, called PRIST (patient record information system tool): a high transportability on different hardware and operating systems, a conversational and interactive user-interface and user independence Relational Data Base Management System (RDBMS). Although we developed PRIST-2 on the top of the ORACLE RDBMS, it does not depend on SQL commercial products because the ORACLE features have been directly used only for SQL relational data base management. The application design methodology implemented in the system architecture allows an interactive and formal description of the application constraints in terms of the semantic data model rather than in terms of the data structure. The translation of the conceptual constraints into SQL tables is performed by several pre-defined routines. In the PC based release (MS/DOS, OS/2, Xenix operating systems), the Graphic-User Interface (GUI) has been developed using Microsoft Windows Software Development Kit. The UNIX release will use a GUI developed on top of the X-Windows environment. PMID- 1889901 TI - European strategies for training in health information systems. AB - The Committee of Ministers of the Council of Europe recently adopted a recommendation on training strategies for health information systems. The main elements were: specific adaptation of training both to the wider health care setting and to the individual work situation; training provided on a multidisciplinary basis; involvement of local health care, educational, research and commercial establishments; setting up of a network of reference centres to facilitate rapid exchange and harmonisation at national and European levels. PMID- 1889902 TI - Adaptive fiducial point detector for ECG stress testing systems. AB - The paper deals with the problem of fiducial point detection in noisy exercise ECG signals. Performance of the averaging process depends on the detector's repeatability. The paper proposes an adaptive algorithm for optimization of the detector. The structure of the detector is well known and often used. Characteristics of the last filter are matched to the current signal and bandpass filter impulse response. The new method was tested using real ECG signals. Results indicated that the FP jittering was reduced to almost one half. PMID- 1889903 TI - Computerized dispensing system: reducing the time of dispensing medicines. AB - We have developed a new computerized dispensing system which reduces the time needed to dispense medicines. This system is so designed to assist the pharmacist with various tasks. These include receiving prescriptions, dispensing of medicines, checking for accuracy, and payment. This system consists of automated dispensing devices, a tray-transfer line, a reception number indicator screen installed in the waiting room, and a terminal to provide patients with additional information. The prescription data are instantly transmitted to the respective dispensing positions and the prescriptions are dispensed simultaneously. The trays travel efficiently on the tray-transfer line. The host computer performs such functions as input of information of prescriptions, accounting calculations, integrating prescription audit, and preparation of printing data for medicine bags. The control computer, which receives prescription data from the host computer, sorts and sends instruction data on prescriptions to the automated dispensing machines, outputs instructions on the preparation of medicines in the manual dispensing sector, and controls the tray-transfer line, the turn tables and the reception number indicator screen. This computerized dispensing system has produced the following results: (1) improvement in the quality of the dispensing work; (2) reduction in the time required for dispensing medicines; (3) improvement in the quality of service to patients; (4) improvement in the efficiency of the clerical work in non-dispensing work; (5) improvement in work efficiency. PMID- 1889904 TI - Formula predicting survival in mice inoculated with leukemia cells. AB - A microcomputer program in BASIC for predicting the survival probability after inoculation of L1210 leukemia cells into mice is designed. Formulas used in this study are derived from the data published by Johnson et al. (J Natl Cancer Inst, 34 (1965) 277-290). A mathematical model and a computer program previously published by the author are employed in this study. Analysis of the computer assisted predicted values and the reported data (J Natl Cancer Inst, 34 (1965) 277-290) on survival probabilities has shown that the program is accurate and reliable with a close agreement in expressing survival probability as a function of inoculum size and time after inoculation. PMID- 1889905 TI - A computer program for the estimation of kinetic parameters of membrane currents based on the Gauss-Newton method. AB - A computer program based on the Gauss-Newton method was developed for the Hodgkin Huxley estimation of kinetic parameters of membrane currents recorded in voltage clamp experiments. Fast potassium current of land snail neurons was estimated, and found to be in agreement with literature reports. PMID- 1889906 TI - MacCueSee: a quality control program for the Macintosh computer. AB - MacCueSee was written to perform routine calculations on quality control concentration values from radioimmunoassay. It is written in Microsoft QuickBASIC for the Apple Macintosh computer. The program calculates within and between assay standard deviation (S.D.) and coefficient of variation from a spreadsheet file containing concentration values of controls analyzed. It also calculates the average concentration +/- 1 S.D. and contraction +/- 2 S.D. to establish between assay ranges. Its flexibility permits varying replicates between assays and automatic exclusion of missed assays. Within assay variability calculations are made for single, duplicate, and triplicate tubes. Results are displayed and can optionally be printed. In addition to radioimmunoassay, MacCueSee can be applied to a number of analytical methods in which quality control is monitored. An example of program use is included. PMID- 1889907 TI - Some software requirements for a PACS: lessons from experiences in clinical routine. AB - In the Department of Radiology of the University of Graz a PACS which includes CT scanners as modalities was installed. Parts (communication and archiving) of this PACS are used in routine work. Summarizing our experiences from routine work we discuss a minimal set of software requirements that a PACS must meet to allow a fast and non-problematic operation concerning communication and archiving. Most of the functionality of the PACS is provided by software processes which are running automatically in the background. These processes convert images into the ACR-Nema format, submit data in the image database and so on. If a process does not work correctly or crashes, it may happen that examinations are only partially or even not archived. If the user recognises a malfunction too late the troubles spread over the whole system and great time delays or loss of data may occur. Examples of such malfunctions are software crashes, interruptions of the connection between 2 processes or a hardware crash. A PACS that is used in routine work should conform to a set of requirements like autonomous supervising of the single processes, automatical elimination of malfunctions, communication with the user and others. Then the PACS will operate without problems and safely. An intelligent process-structure which conforms to these requirements will be discussed. PMID- 1889908 TI - Automatic identification of significant graphoelements in multichannel EEG recordings by adaptive segmentation and fuzzy clustering. AB - A new approach to visual evaluation of long-term EEG recordings is proposed. The method is based on multichannel adaptive segmentation, subsequent feature extraction, automatic classification of the acquired segments by fuzzy cluster analysis (fuzzy c-means algorithm), and on the distinguishing of thus identified EEG segments by colour directly in the EEG record. The black and white variant of the described automatic system is presented. The method was evaluated by applying it to simulated artificial data and to real EEG recordings; some of the illustrative results are shown. In addition, the performance of this system is evaluated and the first experience with its application to routine EEG recordings is discussed. PMID- 1889909 TI - Evaluation of computerized medical diagnostic decisions via fuzzy sets. AB - Two of the greatest obstacles in medical data processing can be summarized as 'multiclass and noncrisp membership of the patterns' and originate from the fact, that one patient can suffer in different degrees from more than one disease simultaneously. Some encouraging results have been obtained applying to these problems a fuzzy pattern recognition model instead of the purely statistical one. A criterion for evaluation of fuzzy classification accuracy has been developed. In this paper, its general form is presented and appropriately discussed. A composed form of the criterion is suggested, which consists of three components - Integral Index of Classification. Highest Discrepancy Index of Classification and Highest Coincidence Index of Classification. Three graphical examples have been designed in order to clear up the underlying idea. The implementation of the criterion is illustrated by experiments with real data from medical practice. PMID- 1889910 TI - Pharmacokinetics of a controlled release preparation of naproxen. AB - The pharmacokinetics of a controlled release preparation of naproxen (750 mg) was compared with that of standard release naproxen, in 12 healthy volunteers. The plasma levels of naproxen and urinary recoveries of naproxen and metabolites were determined both after single doses and chronic administration. The experimental data show that the bioavailability of the controlled release preparation is equal to that of standard release naproxen; however, the controlled release preparation allows more constant plasma levels of naproxen and, when administered once a day for prolonged periods, is capable of maintaining effective concentrations for most of the dosing period. PMID- 1889911 TI - Theophylline-induced increase in plasma uric acid--purine catabolism increased by theophylline. AB - The effect of theophylline on the concentration of uric acid in plasma was investigated. Theophylline increased the plasma concentrations of purine bases (uric acid, hypoxanthine and xanthine) without a decreased urinary excretion of these purine bases in normal subjects. 1-methyl uric acid, a metabolite of theophylline, was not converted to uric acid in a detectable level by the hepatoma-derived cell line HuH-7 cells. Although theophylline affected neither the concentration of nucleotides nor the activities of the enzymes related to purine metabolism (hypoxanthine-guanine phosphoribosyl transferase, 5' nucleotidase, adenosine deaminase and purine nucleoside phosphorylase) in erythrocytes, these results suggested that theophylline-induced purine degradation seems to be a cause of the increased concentration of uric acid in plasma. PMID- 1889912 TI - Reassessment of dapsone as a marker of acetylator phenotypes. AB - The ratio of metabolite to parent dapsone concentrations at 3 hours after dosing has been used as a marker of acetylator phenotypes. The absorption of dapsone is somewhat erratic with peak concentrations often found after the 3-hour determination. The present study done in 30 healthy, male volunteers compared ratios of metabolite to parent dapsone concentrations 3 hours after dosing with AUC values calculated during a 24-hour period as well as extrapolated to infinity. A single oral dose of 100 mg of dapsone was given to fasting subjects and serial blood samples were obtained over a 24-hour period and assayed by high performance liquid chromatography for parent and acetylated metabolite. Dapsone pharmacokinetic parameters of AUC (23.4 +/- 8.6 micrograms.h/ml), half-life (24.8 +/- 11.5 hours) and apparent clearance values (81 +/- 30 ml/min) were consistent with those reported previously. Using established criteria for acetylation phenotyping, 20 percent of the subjects (6 of 30) demonstrated rapid acetylation. Bimodality in the ratios, independent of the experimental indices used to differentiate genetic metabolism, was not readily apparent. The data suggest that large variability in the pharmacokinetics of dapsone may sufficiently obscure the evidence of polymorphic metabolism. The use of dapsone as a marker of acetylator phenotyping should be limited to patient populations. PMID- 1889913 TI - Lack of gastric adverse effects of erdosteine in rats and men. AB - Erdosteine is a thiol derivative endowed with mucolytic, mucomodulator and free radical scavenging properties. Studies were performed in rats and men with the aim to assess its safety on gastric mucous barrier. Two experiments were performed in rats by comparing the effects of erdosteine, homocysteine thiolactone (HTL), carbocysteine, tiopronin and placebo on a) macroscopic appearance of G. I. ulcer, total HCl, pH and volume of gastric juice 4 and 6 hours after, respectively, pylorus ligation in Shay rats and drug oral treatment, and on b) macroscopic appearance of G. I. ulcer in fasting rats for 50 hours, during which the animals received 4 oral doses of each compound. In both conditions erdosteine was completely inactive in the dose-range of 500-1000 mg/kg p.o. while HTL, carbocysteine and tiopronin were ulcerogenic already at the dose of 500 mg/kg p.o. Accordingly, 15 human beings, undergoing gastroscopy, well tolerated erdosteine at the oral dose of 300 mg TID for 9-13 days. In this open study the patients neither revealed worsening of their pre-existing gastric complains, nor indicated new subjective symptoms, nor manifested macroscopic and histological alterations concerning the parietal tonus, the status of epithelial mucosa and of gastric content (including: volume, total acidity and total, bound and free sialic acid). PMID- 1889914 TI - Intrathecal baclofen overdose: report of 7 events in 5 patients and review of the literature. AB - This study is intended to alert the clinician to the insidious symptoms of baclofen overdose, its prevention and treatment. In a group of 43 patients suffering from previously intractable spasticity and a total treatment time of 2,422 weeks, 7 events of intrathecal baclofen overdose happened in 5 patients. On two occasions, a bolus injection caused an overdose (dose 50 and 280 micrograms). The 5 events during continuous infusion intoxication only happened in high dosed patients. The overdose symptoms occurred in one patient when she was lying in supine position (800 micrograms/24 h), in another patient after repair of CSF leakage by an autologous epidural bloodpatch (1,920 micrograms/24 h) and in tolerant patients, once during maximal dose adjustments (2,400 micrograms/24 h) and twice ca. 6 hours following reinitiation of the intrathecal baclofen infusion after a "drug holiday" treatment (27 and 55 micrograms/h). We could not confirm the reported similarity of baclofen overdose with the anticholinergic syndrome. Especially, the bradycardia and hypotension are more in accord with the reported clinical picture of oral baclofen overdose. In the absence of a pure baclofen antagonist and the varying symptoms of intrathecal baclofen, intoxication make rational treatment difficult. We observed that the advised physostigmine therapy is not always effective and safe. The occasionally doubtful antidotal benefits of physostigmine must be weighted against major side-effects. The classical approach of decreasing the absorption of a drug by lowering baclofen levels in the CSF by lumbar puncture drainage was successful. This approach together with conservative symptomatic treatment in an intensive care environment is probably a better and safer alternative than physostigmine alone as an antidote. PMID- 1889915 TI - Recidivism among high-risk youths: study of a cohort of juvenile detainees. AB - We report some results from an ongoing, longitudinal study of juvenile detainees. Analyses were directed toward determining whether the youth's alcohol or other drug use and their emotional/psychological problems at entry into the detention center predicted subsequent arrests for new offenses. Statistically significant relationships were found between the youths' demographic characteristics (age, race, gender), referral history, reason for placement in the detention center, and cocaine use (as measured by urinalysis) and recidivism. However, the magnitudes of these relationships were low to moderate in value, suggesting that a longer follow-up period is needed to more meaningfully study this issue. PMID- 1889916 TI - Impact of chemical dependency on family health status. AB - Previous discussions of the relationship between chemical dependency and family health have been based primarily on clinical observations and on the perceptions of family members rather than on research evidence. In order to systematically document the relationship, this study compared family medical insurance claims 2 years prior to and 2 years following the year in which a family member completed a chemical dependency treatment program. Results indicate a significant decrease in claims following the family member's completion of treatment, thus suggesting a relationship between the chemical dependency of one family member and the health status of other family members. PMID- 1889917 TI - MMPI profiles of impaired nurses. AB - The MMPI profiles of 42 nurses presenting themselves for treatment of alcoholism or opiate addiction in a residential setting were examined. When comparisons were made, no significant differences in this sample emerged based on sex, level of professional training, or drug of choice. Results suggested that a significant elevation emerged on the Pd scale, and the D scale approached clinical significance. The clinical implications of these data as they impact the treatment of impaired nurses are discussed. PMID- 1889918 TI - Sexual dysfunction in female adult children of alcoholics. AB - This study investigated sexual dysfunction and selected related characteristics attributed to female adult children of alcoholics (ACOAs). Using a variety of established measures, data were collected on 30 female ACOAs and 30 non-ACOA control subjects from the general population. The results indicated that female ACOAs manifested lower self-esteem, more distrust, and more sexual dysfunction, compared to the control subjects. These findings provide strong empirical evidence that female ACOAs may be at high risk for experiencing sexual problems. PMID- 1889919 TI - Fear of AIDS among intravenous drug users in London and New York. AB - Intravenous drug users in drug treatment centers in London (N = 89) and New York City (N = 100) were given a 31-item, closed-ended questionnaire which asked them to rate levels of fear they experienced and to note fear-related behavior during the previous 8 weeks. Users reported an awareness of AIDS and had changed their behavior to reduce their risk of contracting the disease. The higher rates of AIDS within the study population in New York were associated with (1) higher levels of fear of AIDS on the part of the subjects interviewed and (2) higher rates of behavior change to limit the risk of contracting AIDS. PMID- 1889920 TI - A comparison of the effects of single- and split-dose methadone administration on the fetus: ultrasound evaluation. AB - A prospective study was conducted to evaluate the effects of oral methadone on fetal activity (body movements, breathing, longest inactive period) for drug dependent pregnant women on methadone maintenance. Seven consenting drug dependent pregnant women between 26 and 37 weeks gestation were enrolled in the study. Pairs of ultrasound observation studies were conducted, before and after single-dose methadone (SDM) treatment and split-dose methadone treatment. There were significant decreases in both body movements (p less than 0.001) and breathing episodes (p less than 0.01), and a significant increase in the longest period of inactivity (p less than 0.001) following SDM. A similar but not significant trend was noted before and after split-dose methadone. The results of the single-dose studies differed significantly from normal controls. However, the results of the split-dose studies were similar to controls. It is recommended that women on methadone maintenance should be offered a split-dose treatment protocol. PMID- 1889921 TI - The Teen-Addiction Severity Index: rationale and reliability. AB - There is an urgent need for a reliable method of evaluating the severity of adolescent chemical abuse and problems related to chemical abuse. The lack of an appropriate rating scale to fill this objective hampers the design and the assessment of objective treatment outcome and follow-up of adolescent chemical abusers. The Teen-Addiction Severity Index (T-ASI) is a structured interview which was developed to assess the seven following domains: chemical use, school status, employment-support status, family relationships, peer-social relationships, legal status, and psychiatric status. This paper discusses the rationale for the design of the T-ASI and presents a preliminary study indicating satisfactory interrater reliability of the rating scale. PMID- 1889922 TI - Behavior and personality traits among DUI arrestees, nonarrested impaired drivers, and nonimpaired drivers. AB - Eight types of drinking driver groups were compared on several personality and behavior traits. It was found that impaired drivers arrested after an accident or moving violation were significantly higher in hostility, psychopathic deviance, nontraffic arrests, frequency of impaired driving, accidents after drinking, and drinks consumed per week than impaired drivers caught in roadblocks. Neither impaired drivers stopped in roadblocks nor impaired drivers never arrested differed from nonimpaired drinking drivers or nondrinking drivers on most measures examined. PMID- 1889923 TI - Prediction of resumption of drinking in posttreatment alcoholics. AB - The ability of five factors (depressive symptomatology, neuropsychological performance, psychosocial maladjustment, previous treatment history, and childhood attention deficit disorder symptomatology) to predict relapse was examined in a follow-up experimental design. Fifty-eight male and 45 female alcoholics were interviewed immediately following release from inpatient treatment units. Fourteen months later, 41 subjects (41%) were classified as resumers; 62 (59%) were abstainers. Resumers showed significantly poorer scores than abstainers on all five of the predictor variables. Discriminant function analysis resulted in 75% correct classification of resumers and abstainers (chi 2 = 22.1, p less than .001). Stepwise multiple regression resulted in isolation of depressive symptomatology as the best single predictor of relapse. PMID- 1889924 TI - Male physical aggression as a function of alcohol, frustration, and subjective mood. AB - An experiment tested the hypothesis that alcohol intoxication will increase aggression only if the subject is experiencing the intoxicated state as displeasing. Forty males drank either 0.8 mL of pure alcohol/kg body weight or a placebo drink and were then exposed to either a pleasant or an unpleasant mood manipulation. Following this, they were given the chance to aggress in a modified version of the Buss "aggression machine" paradigm. All subjects were observed under varying levels of frustration. Results indicated that alcohol-drinking subjects were more aggressive than placebo-drinking subjects, and that both intoxicated and sober subjects increased their aggression when frustrated. Intoxicated subjects in a pleasant mood were most aggressive under both provocative and nonprovocative conditions. The hypothesis was not supported and results are discussed in relation to different theoretical models and in relation to results from other similar studies. PMID- 1889925 TI - Adolescent initiation into drug-taking behavior: comparisons over a 5-year interval. AB - Acquisition curves for six substances were compared for adolescents in two samples separated by a 5-year interval. Individual variations in initiation ages were found for different substances, but the general pattern of exposures to drugs was essentially stable over the time interval. The findings suggest that there appears to be a range of first experience with drugs that extends from 13 to 16 years. Special emphasis was given to the implications which the findings have for education and intervention programs, and for further research. PMID- 1889926 TI - Irish alcoholic women in treatment: early findings. AB - Alcoholic women in Ireland, as in other countries, tend to drink alone and a minority are pub drinkers. There are scant data about alcoholic women who are treated as well as about the outcome of such treatment. A representative sample of women in treatment were interviewed based on consecutive admission to treatment centers in Ireland. The women will be interviewed again 1 year later. Drinking patterns, use of other drugs, parental drinking, and troubles associated with drinking are described. PMID- 1889928 TI - Patient factors related to early attrition from an outpatient cocaine research clinic: a preliminary report. AB - Of 60 cocaine misusers seeking outpatient treatment, 33 (55%) dropped out by 4 weeks. Dropouts were more likely to be male, Black or Hispanic, or with no history of primary depression. Completers were more likely to be White, female, or depressed. The implications of these findings and possible strategies for reducing the dropout rate are discussed. PMID- 1889927 TI - Effectiveness of the Transcendental Meditation program in preventing and treating substance misuse: a review. AB - This article reviews 24 studies on the benefits of Transcendental Meditation (TM) in treating and preventing misuse of chemical substances. Studies cover noninstitutionalized users, participants in treatment programs, and prisoners with histories of heavy use. All the studies showed positive effects of the TM program. Some of the survey-type studies were unable to exclude the possibility of self-selection or responder biases. However, longitudinal, random-assignment studies with objective measures also showed positive results. Taken together, these and other studies indicate the program simultaneously addresses several factors underlying chemical dependence, providing not only immediate relief from distress but also long-range improvements in well-being, self-esteem, personal empowerment, and other areas of psychophysiological health. PMID- 1889929 TI - Sobriety outcome after alcoholism treatment with biofeedback participation: a pilot inpatient study. AB - The effect of the amount of biofeedback training received upon abstinence from alcohol was studied at 3, 6, and 12 months postdischarge for 233 male veterans in an inpatient alcoholic rehabilitation unit (ARU). The frequency of sobriety for those patients with at least 6 training sessions was significantly better than for those with less or no training at all three time periods. The effect was most prominent for those receiving the highest level of biofeedback training (8+ sessions), and at the earlier time frame (3 months). The discussion focused upon the implications for overall rehabilitation programming for the alcoholic and on factors involved in the efficacy of biofeedback therapy. PMID- 1889930 TI - Development and evaluation of the revised Alcohol Evaluation Instrument. AB - This study reports on the development of a revised version of the Alcohol Evaluation Instrument (ALCEVAL-R). Items in the four major areas of the ALCEVAL-R were factor analyzed separately and relationships among factors were examined. Results suggest that the ALCEVAL-R measures clinically meaningful aspects of the alcoholic patient's occupational and social status, and reveals important dimensions of alcohol consumption and of the personal and social consequences of alcohol abuse. PMID- 1889931 TI - Is there an epidemic of drug misuse in Brazil? A review of the epidemiologic evidence (1977-1988). AB - A critical review is presented of methods and findings of epidemiological studies on drug use carried out in Brazil. Studies of the first phase (1977-1986) suffered from serious flaws but tended to produce inflated rates, as compared to studies conducted after 1987, which used better case definition criteria and sampling strategies. Prevalence of consumption of legal substances was comparable to industrialized countries but lifetime use of illicit drugs in the country tended to be much lower. In conclusion, there is no support from epidemiologic studies for the hypothesis of an epidemic of drug addiction in Brazil nowadays. PMID- 1889932 TI - The behaviour of the plasma free testosterone/cortisol ratio during a season of elite rowing training. AB - During nine months of training preceding the 1988 Olympic Games, six elite male rowers were regularly subjected to an investigation to changes in the rest values of the free testosterone/cortisol ratio (FTCR). In addition, the rowers were subjected to an exercise test on rowing ergometer. When comparing the FTCR levels through the season with the initial level, the results show that during periods of heavy training (training camp) the rest levels of the FTCR decrease (range 5 50%) in most of the rowers. During periods of less intensive training, the opposite is the case for the behaviour of the FTCR. The FTCR value never dropped below 0.35*10(-3), a value which is considered to be the threshold of overstrain. Moreover, decreases in the FTCR of more than 30% relative to preceding values were often found. These decreases are not indicative for overstrain but should be related to temporary incomplete recovery from intensive training. However, it remains to be demonstrated that periods of prolonged decreases (several months) in the level of the FTCR may finally lead to a situation of overstrain or overtraining in an athlete. Power at 4.0 mmol lactate (P4.0) and maximal power (PM) did not show a relation with the hormonal parameters. PMID- 1889933 TI - Beta-endorphin time course response to intensity of exercise: effect of training status. AB - The concentration of beta-endorphin (B-EP) was measured in 6 trained and 6 untrained cyclists during three intensities of exercise to determine the time course changes of B-EP. B-EP was determined by radioimmunoassay with less than 5% cross reactivity with beta-lipotrophin. A counter-balanced design was used to avoid an order effect from exercise intensity. Resting B-EP values were similar across visits. There were no differences in resting B-EP values comparing the trained (4.61 +/- 0.25 pmol.l-1) to the untrained (4.03 +/- 0.23 pmol.l-1) group. Cycling at 60% VO2max did not increase B-EP in either group at any time measured. Cycling at 70% VO2max increased B-EP by 10 min in both groups p less than 0.05. The rate and magnitude of increase of B-EP were similar for both groups. B-EP changes at 80% VO2max were significantly greater that at 70% VO2max and were identical for the two groups. Both groups demonstrated increases by 5 min and further increases at 30 min of exercise p less than 0.01. These changes occurred despite the fact that lactate levels were lower in the trained group at both 70 and 80% VO2max intensities. It is concluded that the time course change for B-EP is similar for trained and untrained individuals working at the same relative intensity of exercise and does not seem to be related to plasma lactate concentrations. PMID- 1889934 TI - Failure to induce ovulation with clomiphene citrate and bromocriptine in luteal deficient women athletes. AB - This study was designed with a three-fold aim: to assess ovarian function of women athletes with menstrual irregularities (AMI); to evaluate the potentiality of clomiphene citrate and bromocriptine for the induction of ovulation in these women; and to show that ultrasound scanning offers a suitable technique for ovarian screening in healthy and high-performance athletes. Our small test group consisted of 11 women, mainly track athletes, with AMI. There was no significant difference in age at menarche (13.2 yrs +/- 0.2), percent of ideal body weight (92% +/- 4), or percent of body fat (12.3% +/- 2.8) among the subjects. Plasma estradiol values were low (mean: 22 pg/ml +/- 0.8), as those of plasma progesterone (2.85 ng/ml +/- 2.10), LH (5.6 mIU/ml +/- 0.8), and prolactin (10.89 ng/ml +/- 5.56). The mean distance run per week (35 km +/- 15) was relatively high considering the presence of 4 non-runners. All menstrual irregularities were attributed to exercise. A short luteal phase (7 days +/- 1.5 for a cycle with a mean duration of 25 days +/- 1.8) was found in all subjects. We failed to observe the presence of a corpus luteum in 9 out of 11 women. A two-month administration of clomiphene citrate (150 mg/d for 5 days) or bromocriptine (2.5 mg/d) did not succeed in provoking ovulation in any of these women. Ultrasonographic observations showed a continuously hypo-estrogenic endometrium with a consecutively developing and regressive follicle. Our data emphasize the difficulties inherent in the restoration of menstrual function in women athletes with AMI. In addition, the usefulness of ultrasound in screening ovarian function was confirmed. PMID- 1889935 TI - Phagocytic function of blood neutrophils in sedentary young people after physical exercise. AB - The effect of exhaustive running exercise on the phagocytic function of blood polymorphonuclear neutrophils in sedentary young men and women has been studied. Adherence capacity to the endothelium, spontaneous mobility, chemotaxis and ingestion of Candida albicans were not modified after physical exercise. However, opsonization of Candida albicans as well as candidicide power increased significantly in men and women after exercise. The immediate advantages of physical exercise on the phagocytic immune response is discussed. PMID- 1889936 TI - Organization of segmental reflexes in trained dancers. AB - Unilateral and conditioned Achilles tendontap reflex (ATR) characteristics were examined in a group of skilled dancers and a group of sedentary, untrained subjects (n = 7/group). For the conditioned reflex, the right ATR was conditioned by a tap to the left Achilles tendon using intervals of 10, 40, 70, 100, 130, 160 and 190 ms. Peak isometric force, contraction time and half-relaxation time were examined on each trial. The results indicated that the trained dancers exhibited less unilateral isometric force and longer half-relaxation times (p less than 0.05) than the untrained subjects. Moreover, the contralateral conditioning stimulus caused a more marked short-latency facilitation as well as a long latency inhibition in the reflex force characteristics for the trained dancers when compared with the untrained subjects. These differences in both simple and conditioned reflexes in individuals trained for dance activities may reflect differences in muscle stiffness, tissue compliance or neural organization. PMID- 1889937 TI - Prolonged peroneal reaction time in ankle instability. AB - The peroneal reflex time to sudden ankle inversion and the postural control of 15 athletes with functionally instable ankles were compared with 15 stable controls. A trapdoor produced sudden ankle inversion. Surface electrodes recorded electromyographic activity of the peroneal muscles. Postural sway was expressed by a transverse sway value obtained during single limb stance on a force plate. Increased postural sway was found in subjects with functional instability (p less than 0.01). This is in accordance with previous studies. Functionally instable subjects also displayed an increased peroneal reaction time (p less than 0.01) supporting the theory that functional instability is induced by a proprioceptive reflex defect. Nine of the 15 instable subjects were unilaterally instable and showed lower peroneal reaction time and postural sway values for the stable ankle, but the difference was not significant. There was a high degree of correlation between postural sway and peroneal reaction time (Spearman's rho = .92). In ten functionally instable athletes tested with and without ankle taping, it could not be verified that a reflex enhancing effect of taping occurs through stimulation of cutaneous afferents. PMID- 1889938 TI - Visual evoked potentials: differences related to physical activity. AB - Visually evoked potentials to patterned stimuli were recorded from tennis players, rowers and non-athlete control subjects. Each group consisted of 12 males and 12 females of similar age. Tennis players showed shorter P100 latencies compared to those of control subjects and rowers. This difference exists, in the same range, both in the male and in the females. The analysis of covariance and multiple linear regressions show that these shorter latencies cannot be explained by head circumference or by height. The hypothesis of a relationship between these shorter latencies and the specific qualities of racket players is suggested. A second experiment with squash players seems to confirm these first results. PMID- 1889939 TI - Variations in stride length and running economy in male novice runners subsequent to a seven-week training program. AB - The purposes of this investigation were to document the changes in stride length of college-age male novice runners (n = 13) who were allowed of freely choose their stride length throughout a 7-week training period (FCSL), and to compare subsequent changes in running economy to those observed in a similar group of runners (n = 13) that ran for 7 weeks with constant stride lengths equivalent to their initially chosen stride lengths (CSL). Subjects trained 3 days per week for approximately 7 weeks (22 training bouts). Each training bout consisted of a minute warmup (60% VO2max) and a 15-minute run at a speed equivalent to 80% of the subjects' initial VO2max. Absolute stride length (ASL), heart rate (HR), and ratings of perceived exertion (RPE) were measured during the 12th and 20th minute of exercise. Relative and absolute submaximal VO2 were measured during the 4th and 22nd training bout. No significant differences in percent change in ASL were found between the groups or across the weeks of training at the 12th or 20th minute of exercise; however, there was a significant difference (p less than or equal to .05) between the groups during the 4th week of training. No significant differences were found between the groups in relative or absolute submaximal VO2. Relative submaximal VO2 at the 12th minute of exercise decreased significantly following the training period in both the FCSL (-3.38%) and CSL (-4.32%) groups. Absolute submaximal VO2 did not change significantly following the training period.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1889940 TI - Physiological responses at the fatigue threshold. AB - The purpose of this investigation was to determine the oxygen consumption, heart rate and plasma lactate responses at the fatigue threshold (FT) and estimate the length of time the FT could be maintained. Ten adult males (mean age +/- SD = 21.1 +/- 1.3 yrs) volunteered to perform a maximal treadmill test and FT test. During the maximal test, VO2 heart rate and plasma lactate measurements were taken. The results of the investigation indicated that the FT (14.0 +/- 1.2 km.hr 1, 197 +/- 8 bpm; 47.5 +/- 5.7 ml/kg.min-1, 5.4 +/- 1.3 mM) was very close to a maximal effort (VO2max = 14.4 +/- 1.2 km.hr-1, 203 +/- 10 bpm; 49.5 +/- 6.1 ml/kg.min-1, 7.4 +/- 2.1 mM) and could be maintained for only 0.16 to 0.28 hrs. These findings do not support the validity of the FT as a measure of the maximal running velocity that can be continued for an extended period of time without exhaustion. PMID- 1889941 TI - Peak heart rates during maximal running and swimming: implications for exercise prescription. AB - Thirty-four college-age fitness swimmers, 19 males and 15 females, were maximally tested during treadmill running (TR) and tethered swimming (TS). A discontinuous, graded test protocol was used for both TR and TS with 2-min stages and 1-min rest periods. Peak HRs were obtained via a UNIQ CIC monitor during the last 120 s of each stage. Blood lactate was measured at 3 min post exercise using a YSI Model 27 Analyzer. TS peak HR was significantly lower (p less than 0.05) than both the age-predicted HRmax (220-age) and TR peak HR by 13 and 11 bt.min-1, respectively. Blood lactate for TS (8.0 mmol.l-1) and TR (8.1 mmol.l-1) were similar. Mean target heart rate range (THRR) calculated from TS peak HR (144-176 bt.min-1) was significantly lower than THRR calculated from age-predicted max HR (151-187 bt.min-1) and TR peak HR (151-186 bt.min-1). For young adult fitness swimmers, we suggest reducing the HRmax obtained from treadmill exercise or predicted from age by 12 bt.min-1. This correction appears to be a reasonable estimate of swimming HRmax that can be used for calculating exercise intensity. PMID- 1889942 TI - Evidence for an alveolar-arterial PO2 gradient threshold during incremental exercise. AB - Examination of the alveolar-to-arterial O2 tension (A-a PO2 difference) provides a method of examining the efficiency of pulmonary gas exchange during exercise. At present, considerable confusion exists as to the exact pattern of the A-a PO2 difference during incremental exercise. We tested the hypothesis that the A-a PO2 difference during incremental exercise is alinear with respect to metabolic rate. Measurements of the A-a PO2 difference were made on six healthy male subjects during incremental exercise under sea level conditions (PIO2 = 149 torr). An alinear model best described the relationship between the A-a PO2 difference and metabolic rate; only small increases in the A-a PO2 difference occurred at low work rates followed by a rapid increase at higher work rates. The existence of a "A-a PO2 difference threshold" was mathematically confirmed by the use of a computer algorithm to define inflection points. These data provide evidence that the relationship between the A-a PO2 difference and metabolic rate is alinear and that a metabolic threshold exists for a rapid increase in the A-a PO2 difference. We conclude that the efficiency of pulmonary gas exchange during exercise is unaltered from rest during low-to-moderate power outputs, however, high intensity exercise compromises pulmonary gas exchange efficiency as evidenced by a significant widening of the A-a PO2 difference. PMID- 1889943 TI - Metabolic and cardiorespiratory responses to the performance of Wing Chun and T'ai Chi Chuan exercise. AB - The primary purpose of this study was to examine the metabolic and cardiorespiratory responses to the continuous performance of Wing Chun and T'ai Chi Chuan exercise. No significant differences in VO2max or HRmax obtained during treadmill exercise were found between the practitioners of the two styles. Average values for oxygen uptake (VO2) were 23.3 +/- 7.5 ml.kg-1.min-1 (6.6 METS) and 16.0 +/- 3.9 ml.kg-1.min-1 (4.6 METS) for Wing Chun and T'ai Chi Chuan exercise, respectively. Mean heart rates obtained during exercise were 137 +/- 25 beats.min-1 for Wing Chun and 116 +/- 22 beats.min-1 for T'ai Chi Chuan exercise. These exercise values corresponded to 52.4% of VO2max and 70.5% of HRmax for Wing Chun and only 36.4% of VO2max and 59.8% of HRmax for T'ai Chi Chuan exercise. Thus, only the continuous performance of Wing Chun exercise elicited VO2 and HR responses that would be expected to bring about a cardiorespiratory training effect in subjects with a relatively low initial VO2max. The ventilatory equivalent for oxygen (VE/VO2) obtained during T'ai Chi Chuan exercise (21.7) was significantly lower than for Wing Chun exercise (24.2), suggesting that T'ai Chi practitioners utilize efficient breathing patterns during exercise. Both Wing Chun and T'ai Chi Chuan styles may have a small static component that produces a slightly elevated heart rate relative to metabolic load when compared to traditional aerobic activities. However, the effect was not severe and these forms of exercise should not be considered dangerous for individuals at high risk for cardiovascular disease. PMID- 1889944 TI - Mineral and vitamin intake in field athletes (discus-, hammer-, javelin-throwers and shotputters). AB - Thirty field athletes (discus-, hammer-, javelin-throwers and shotputters) were studied. Dietary intake was determined by using the seven-day estimated dietary record. Analysis of the dietary intake indicated that on average, the males (n = 20) consumed adequate amounts of micro-nutrients. The mean intake for the females (n = 10) were adequate for phosphorus, zinc, vitamin A, thiamin, riboflavin, nicotinic acid, vitamin B6, folic acid, vitamin B12 and vitamin C. Some of the females did not consume adequate amounts of calcium, iron, and magnesium. These dietary deficiencies can be corrected through proper food choices and by consuming a great variety of food. Athletes (especially the females) should be educated on their nutritional needs, good dietary practices, and planning adequate diets for training and performance. PMID- 1889945 TI - The concentration of lactic acid in breast milk following maximal exercise. AB - The purpose of this study was to investigate the concentration of lactic acid in breast milk following maximal exercise. Seven active postpartum women (2 to 24 months) were exercised to maximum on a treadmill (VO2 max = 37.0 +/- 13.7 ml.min 1.kg-1). Blood was sampled via finger prick at rest before exercise and 5 minutes postexercise; milk was collected via self expression at rest before exercise and at 10 and 30 minutes postexercise. Both blood and milk were analyzed for lactic acid via enzymatic methods. Following maximal exercise, a significant increase in the concentration of lactic acid was found in the blood at 5 minutes postexercise and breast milk at 10 minutes postexercise. Although elevated, the lactic acid concentration of the 30-minute sample of breast milk was not significantly different from the resting sample. Maximal exercise can result in significant increase in lactic acid concentration in breast milk. Further research is needed to demonstrate whether the taste of the milk is affected. PMID- 1889946 TI - Development of runner's anemia during a 20-day road race: effect of iron supplements. AB - Intense training for long-distance running has been associated with reduced hemoglobin (Hb) levels and low iron stores. Whether iron supplementation helps prevent this "runner's anemia" remains controversial. To determine the relationship between iron status and the early stage of reduced Hb levels in male runners, we examined hematologic variables in 15 healthy men (ages 25 to 47 yrs) who ran twice their regular training distance in 20 days during a 500-km road race. Nine of the runners took iron-containing tablets which provided an average of 36 mg/d of iron, while the other six did not take iron supplements. Only one of the 15 subjects had a low Hb concentration (less than 14 g/dl) before the race. After 10 days (285 km), low Hb levels (p less than 0.001) were found in 12/15; six of these runners took iron supplements. However, following a 2-day rest period and five more days of running, only 5/15 and 7/15, respectively, had low Hb levels. Serum iron, ferritin, total iron binding capacity, and percent transferrin saturation values remained within normal limits and did not change significantly. Reticulocyte counts progressively increased, becoming 8-fold higher than at baseline (p less than 0.001), irrespective of the use of iron supplements. "Runner's anemia" developed in 11/15 (73%) of the subjects, independently of their iron status and iron intake. The reductions in Hb were accompanied by parallel decreases in RBC count and hematocrit, and by a significant reticulocytosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1889947 TI - Psychological aspects of psychogenic deafness in children. AB - Twenty-nine children with psychogenic deafness were investigated from audiological and psychological aspects. ABR and Bekesy audiometry were useful for diagnosing psychogenic deafness. The elapsed time from the start of treatment to audiometric recovery was significantly shorter in patients receiving psychological treatment, indicating that treatment by a team of otologists and counselors was able to hasten recovery in children with psychogenic deafness. The pattern of hearing recovery in the treated group was classified into 3 types and in the control group into 4 types. Counseling seemed to have a positive effect on patients with fluctuating improvement. In the patients in the treated group, the elapsed time to audiometric recovery from the beginning of psychological treatment was 7.5 months; however, in the control group recovery it took 17.1 months. Psychological treatment revealed that the clinical course of psychogenic deafness in children seemed to have some relation to the patient's personality and psychological stresses. PMID- 1889948 TI - Adverse perinatal factors in the causation of sensorineural hearing impairment in young children. AB - The study involves aetiological evaluation of various adverse perinatal causes leading to bilateral sensorineural hearing impairment in children born during the 5-year period of 1981-1985 (inclusive) in the Greater Manchester area of England, United Kingdom. This group comprised over 12% of the total number of hearing impaired children in the area. Individual possible adverse factors are discussed in the light of present understanding of the pathogenesis and previous reports. PMID- 1889949 TI - Eustachian tube function in otitis-prone and healthy children. AB - To evaluate the significance of Eustachian tube function in recurrent acute otitis media (rAOM), 50 otitis-prone children (greater than 11 episodes of AOM) were compared with 49 children without rAOM. Tubal function tests were: initial middle-ear pressure, active tubal function (muscular opening function), passive function (pressure opening and closing levels), and inflationary and deflationary capacity. The otitis-prone children were found to have significantly poorer active tubal function than controls. Other test results did not differ between the two groups. The otitis-prone children were also divided into subgroups with and without intermittent secretory otitis media (SOM), and with and without allergy, but no differences in tubal function tests were found between the different subgroups. The findings suggest active tubal function to be the most significant variable regarding proneness to rAOM, but not to distinguish between particular subgroups of otitis-prone children. The available technique for testing Eustachian tube function is insufficiently sensitive, however, to be conclusive in individual cases, and it is still not possible to predict individual outcome of the illness from tubal function test results alone. PMID- 1889950 TI - Management of epistaxis in children. AB - A randomised clinical trial of antiseptic nasal carrier cream (Naseptin) and silver nitrate cautery in the treatment of epistaxis in children was carried out. Fifty-four percent responded to cautery with silver nitrate and 50% to treatment with Naseptin antiseptic carrier cream. There were 24 patients in each group. No statistically significant difference was observed between the groups when tested with the chi 2 test. We believe that the first line treatment of epistaxis in children should be the use of antiseptic nasal cream. PMID- 1889951 TI - Inner ear damage from toy cap pistols and fire-crackers. AB - Groups of guinea pigs comprising 7 animals in each group were exposed to 10, 50 or 100 exposures to fire-crackers or 10, 50 or 100 exposures to toy cap pistol shots. An additional group of 7 animals comprised the control material. The exposures were performed with 15-s intervals at 0.25 m distance for the toy cap pistol shots and at 0.8 m for the fire-crackers. The peak sound level at the ear was 155 dBC for both impulsive sounds. After a 3-week survival period the animals were anesthetized and decapitated. The cochleas were examined histologically in surface preparations and read double-blind. One animal in each group exposed to 10 fire-crackers and 10 toy cap pistol shots showed sensory cell loss. With 50 or 100 toy cap pistol shots or fire-cracker exposures, 24 out of 28 animals showed pronounced sensory cell loss. The present results clearly indicate the risk for noise-induced hearing loss in children playing with toy cap guns and fire crackers. PMID- 1889952 TI - Problems in diagnosis and treatment of cholesteatoma in children. AB - Our clinical study includes 56 cases of cholesteatoma in children aged 3-14 years, treated in a 6-year period. Cholesteatoma was localized in attic (6 cases), in middle ear (6 cases), in attic plus middle ear (16 cases) and in attic + middle ear + mastoid (28 cases or 50% of the total number). In the surgical treatment combined approach tympanoplasty (intact canal wall technique) was used in 76.8%, radical tympanomastoidectomy in 16.1%, and other techniques in 7.1%. Intact ossicular chain was found in 25%. Reconstruction of the ossicular chain (including autograft, homograft and allograft material) was done in 59%, and the remaining 16% were treated by classic radical surgery. Hearing results: unchanged, 48%; improved, 45%; slightly worsened, 7%; and no dead ear. Recurrency in 31% is considerably higher as compared to 15% in adults found in another comparable study by us. PMID- 1889953 TI - Laryngeal pathology in hearing-impaired children. AB - Eighty-five children enrolled in a total communication elementary school for the severe-to-profoundly hearing-impaired were evaluated prospectively to assess the incidence of laryngeal abnormalities. Direct flexible laryngoscopy and indirect mirror laryngoscopy revealed vocal cord nodules in 3 children, omega-shape infantile epiglottis in 3 children, and normal larynges in the remaining 79 children. These findings suggest that severe-to-profoundly hearing-impaired children develop detectable laryngeal pathology at approximately the same frequency as previously reported by others for normal hearing children. PMID- 1889954 TI - An enteric duplication cyst occurring in the anterior two-thirds of the tongue. AB - Enteric duplication cysts are cysts that are attached to the alimentary tract and that are lined by some type of gastrointestinal mucosa. Such cysts are especially rare when found in the oral cavity. We report the case of an 8-month-old female with an unusual duplication cyst in the anterior two-thirds of the tongue. Eighteen cases of intraoral cysts have been previously reported in the literature, this one being the 7th case of a true duplication cyst of the anterior two-thirds of the tongue which contains gastric mucosa. The case presents many aspects of the diagnosis and management of this unusual lesion. The literature and present etiological theories are discussed. PMID- 1889955 TI - The pencil grip technique for middle ear effusion aspiration. PMID- 1889956 TI - Flexible laryngoscopy in neonates and infants: insertion through a median opening in the face mask. AB - The most common reasons for laryngoscopy in newborns and infants are inspiratory stridor and/or dyspnea. With the help of flexible endoscopes, especially with instruments of diminished diameter, laryngoscopy can be carried out even in premature newborns. We report on a technique of flexible laryngoscopy without the need for restraint and with improved safety. A modified face mask is used for endoscopy. An additional hole is made into the mask with a 4.5 mm drill. It is located in the midline just above the nostrils, about 2.5 cm above the ventilation opening. The flexible endoscope is passed into the nose and pharynx with ease. It does not interfere with the anesthetist's ventilation by the mask. In inhalation anesthesia with halothane, 100% oxygen is supplied. The larynx remains in its physiological position. The head is not retroflexed, and the tongue is not supported by an endoscope as in direct laryngoscopy. No muscle relaxation is used, and muscular activity of the larynx can be observed during spontaneous and assisted ventilation. PMID- 1889957 TI - Early treatment of orbital floor fractures with catheter balloon in children. AB - Fifteen pediatric patients with orbital floor fractures were successfully treated early, following injury by a transantrally introduced catheter-balloon technique. The latter stabilizes and supports the torn, but still vascularized periosteum at the edges of the fracture and also serves as a guide for its further proliferation and new bone formation. Apart from a transient anesthesia in the dermatome of the infraorbital nerve in certain patients no complication or sequela was noted in this series. Accordingly early repair with the use of catheter-balloon appears to be a viable alternative in the repair of orbital floor fracture in children. PMID- 1889958 TI - Modulation of serotonin-induced vasospasm by endothelium and monoamine oxidase. AB - Endothelial modulation of flow induced by intraluminal serotonin (5-HT) in isolated and perfused bovine coronary artery segments was studied. A constant pressure continuous perfusion apparatus was utilized. Control coronary arteries were perfused with a fixed volume of serotonin-containing solution followed by a serotonin-free solution, and flow-rate changes during onset and relaxation of vasospasm were measured. Both monoamine oxidase inhibition by iproniazide and endothelium disruption by collagenase increased the rate of onset and magnitude of vasospasm. When the endothelium was intact the vasospasm continued to increase, reaching maximum well after the end of the serotonin perfusion, followed by slow relaxation toward baseline. This contrasted with de endothelialized vessels in which the increase in contractile response terminated abruptly at the end of the serotonin perfusion and returned rapidly to baseline. Coronary arteries stimulated with prostaglandin F2 alpha responded similarly to de-endothelialized vessels stimulated by 5-HT, although further de endothelialization of F2 alpha-stimulated vessels showed increased rates of onset and relaxation of vasospasm, suggesting a physical barrier role for the endothelium towards unmetabolized agents. These observations are consistent with the hypothesis that endothelial cells are capable of taking up, storing and subsequently releasing serotonin. The results suggest a protective role of the endothelium as a metabolic and physical barrier. This may represent an anatomical substrate favouring the development of localized vasospasm at sites where the endothelium is injured. PMID- 1889959 TI - Influence of 4-hydroxynonenal on bombesin-induced stimulation of phospholipase C activity in rat liver. AB - The influence of 4-hydroxynonenal (HNE) on bombesin-induced PIP2-phospholipase C activity (PL-C) was studied in vitro on isolated liver membranes. Both bombesin and HNE stimulated the enzymatic activity at micromolar concentrations and their effect was enhanced by the nucleotide GTPgammaS. An additive synergism was observed with 1 microM bombesin and 0.1 microM HNE. When GTPgammaS was added to the reaction mixture, the degree of PL-C stimulation in the presence of both compounds was not different from the activity value induced by bombesin alone. Since such micromolar amounts of HNE can be actually found in normal liver cells, these results support the hypothesis of a physiological importance of lipid peroxidation in the regulation of phospholipase-C activity. PMID- 1889960 TI - Antidyslipaemic action and role of CoA in lipid metabolism of mitochondria and peroxisomes. AB - Our study has evaluated the effect of the parenteral administration of CoA on the pattern of haematic lipids and on palmitate oxidation in liver mitochondria and peroxisomes of rats made hyperlipaemic with a high fat diet with or without CoA. Lipid fractions, total cholesterol, triacylglycerols, total lipids and nonesterified fatty acids (NEFA) were determined in blood. Palmitate oxidation was determined in liver peroxisomes and mitochondria incubated in modified Krebs Henseleit solution with 100 microM 1-14C palmitate in the presence and absence of some cofactors. Our results show that in rats fed with a high fat diet there was an increase of all lipid fractions. The increase of all lipid components was lower in animals treated with CoA. In liver peroxisomes of rats fed with high fat diet an increase in palmitate oxidation, that is higher when CoA is parenterally administered, was observed. In addition, palmitate oxidation in mitochondria of rats treated with CoA reached values higher than those of control and of rats fed with a high fat diet without CoA. PMID- 1889961 TI - Effect of propionyl carnitine on energy charge and adenine nucleotide content of cardiac endothelial cells during hypoxia. AB - Adenine mucleotide metabolism is very active in endothelial cells. These cells are very rich in xanthine oxidase which may produce oxygen reactive species during ischaemia and reperfusion when a high amount of adenine nucleotides may be catabolized to hypoxanthine. We investigated the effect of propionyl carnitine on energy charge and nucleotide content in cultured endothelial cells during changes in oxygen partial pressure. During hypoxia the adenine nucleotide pool and the energy charge decreased more slowly in the presence of 0.5 mM propionyl carnitine than in the absence of the compound. Furthermore during reoxygenation a more rapid increase of energy charge and adenine nucleotide concentration was observed with propionyl carnitine. These observations suggest that the presence of propionyl carnitine allows the endothelial cells to maintain their functionality and regulatory role on vessel activity for a longer time and decreases the formation of oxygen reactive species due to xanthine oxidase activity on hypoxanthine formed by adenine nucleotide catabolism. PMID- 1889962 TI - Protective effect of propionyl carnitine against peroxidative damage to arterial endothelium membranes. AB - Endothelial cells may be damaged by oxygen reactive species produced by granulocytes, by transition metal ions or by xanthine oxidase, an enzyme present in great quantity in these cells. Since it has been observed that propionyl carnitine protects the heart from peroxidation, we have investigated the effect of this compound on the formation of thiobarbituric acid reactive oxidation products (TBAR) in endothelial membranes. The peroxidation systems used were a mixture of Fe3+ and Fe2+, hydrogen peroxide and Fe2+, or xanthine oxidase-- xanthine. Propionyl carnitine at millimolar concentrations decreases TBAR formation. The protection is concentration-dependent and is almost absent in the presence of propionate and carnitine. From these results it appears that propionyl carnitine may protect not only myocardium but also vessels from peroxidative damage that occurs during ischaemia and reperfusion. PMID- 1889963 TI - Effects of metoxibutropate, ibuprofen and guaiacol on the gastrointestinal system. AB - In previous studies we have shown that ibuprofen, guaiacol and the guaiacol ester of ibuprofen (I.N.N. metoxibutropate) are able to inhibit in-vitro prostaglandin synthesis. In the present study we have evaluated the effect of ibuprofen, guaiacol and metoxibutropate on the gastrointestinal system. Oral treatment with equimolar increasing doses of the three drugs produced a progressive inhibition of prostaglandin biosynthesis in the intestinal tract, without any effect on the rate of intestinal propulsion. Further studies evaluated the gastric tolerance of a molar dose of ibuprofen causing ulceration in 50% of the animals. After single and repeated administration of guaiacol and of the guaiacol ester of ibuprofen, the percentage of animals with gastric damage was very low and the index of ulceration seemed rather moderate. Our results show that although guaiacol is able to inhibit prostaglandin biosynthesis like a classic NSAID, it does not induce gastric damage. For these reasons it is justified to combine guaiacol with ibuprofen in order to reduce gastric erosions induced by a classic antiinflammatory drug. PMID- 1889964 TI - Adrenal incidentalomas: what is the role of fine needle biopsy? AB - A series of 13 patients with incidental adrenal mass discovered by computed tomography or/and ultrasound is reported. In 5 cases endocrine evaluation and radiological criteria suggested the diagnosis of the mass. In 8 cases we carried out fine needle biopsy (FNB) under ultrasound guidance. FNB confirmed in two cases the presence of metastatic diseases, in one case adrenal adenoma, in other two cases myelolipoma and in one case lymphoma. Surgical exploration was avoided in all cases. In two cases the presence of an asymptomatic adrenal carcinoma and of a giant adenoma, potentially malignant, was demonstrated by FNB. None of the patients underwent surgical exploration as a final diagnostic measure. In conclusion, FNB may represent a useful tool to select the best modalities of treatment. PMID- 1889965 TI - Failure of blood pressure control by a new combined alpha- and beta-blocking agent (amosulalol) in a patient with pheochromocytoma. AB - A 42-year-old woman with pheochromocytoma received preoperatively a combined alpha- and beta-adrenoceptor blocking agent, amosulalol, exerting some inhibitory action on both receptors. Severe hypertension and remarkable fluctuation of heart rate occurred following this medication. Although it is claimed currently that a combined blocking agent is useful for the management of this disease, it should be administered with caution. PMID- 1889967 TI - Sodium, potassium and chloride concentrations in the inner nucleus and outer crust parts of urinary tract calculi. AB - In this study sodium, potassium and chloride concentrations were analysed in the nucleus and crust parts of various kinds of urinary tract calculi. Concentrations of these elements in the nucleus were found to be higher than those in the outer crust part. Moreover, some intra- and inter-correlations were established among the elements mentioned in these two parts of the stones. It was also determined that sodium, potassium and chloride concentrations in the nucleus and crust of various urinary tract stones exhibited statistically significant differences. PMID- 1889966 TI - Acute changes of serum markers for tissue damage after ESWL of kidney stones. AB - Seventeen serum markers (including 9 enzyme activities) for eventual tissue damage were studied after ESWL in 40 patients with unilateral kidney calculosis. No changes were established in the 8 non-enzymic parameters and the activities of amylase, lipase, AST (GOT), ALT (GPT) and CK-MB. A statistically significant increase was found in LDH, alpha-HBDH, CK (twice) and glutamate dehydrogenase (3 times). The slight elevation of LDH and alpha-HBDH could be due to haemolysis caused by the shock waves. Increased activity of CK suggested myolysis and that of GlDH a hepatocellular damage. PMID- 1889968 TI - Diclofenac sodium and spasmolytic drugs in the treatment of ureteral colic: a comparative study. AB - Forty-nine patients with ureteral colic were included in this prospective double blind study investigating the analgesic efficacy and side effects of a prostaglandin synthetase inhibitor Diclofenac sodium (Voltaren) versus a spasmolytic drug Tropenzilium bromide (Palerol). The analgesic efficacy and side effects of the calcium antagonist Nifedipine (Nidilat) applied sublingually in ureteral colic were also investigated. It was concluded that diclofenac sodium was more efficient for relieving pain due to acute ureteral obstruction and had fewer side effects than spasmolytic drugs. Nifedipine proved to have an analgesic effect equivalent to that of Tropenzilium bromide. PMID- 1889969 TI - Evaluation of the course of pregnancy, delivery and the condition of the newborn infant in women operated on for vesicoureteral reflux in childhood. AB - Evaluation of the course of pregnancy, delivery and the condition of the newborn infant in mothers after an antireflux operation performed in childhood has revealed differences to the disadvantage of women operated on after the age of ten. This is shown by a significantly more frequent incidence of EH gestosis and urinary tract infections. Pregnancy intensifies the already existing renal insufficiency but does not adversely affect an efficient kidney. No significant differences have been observed in fertility, way of delivery termination, and the newborn's condition between the studied and the control groups. PMID- 1889970 TI - Histological analysis of high-grade superficial bladder tumour. AB - Segmental cystectomy or total cystectomy was performed in 26 patients with newly diagnosed stage T1, grade 3 transitional cell carcinoma of the bladder. Their histological specimens were assessed with regard to types of tumour cell spread, small vessel involvement and coexistent carcinoma in situ. Patients were followed for 12 to 141 months. Broad front type and tentacular type spread were seen in 57.7% and 38.5%, respectively. Small vessel involvement was seen in 38.5% of patients. Coexistent carcinoma in situ was found in as many as 65.4%. Urethral recurrence was found in 4 patients out of 26. These data suggest that the high incidence of coexistent carcinoma in situ may be the most important cause of the unsatisfactory prognosis for stage T1, grade 3 bladder cancer. PMID- 1889972 TI - Malakoplakia of the prostate. AB - Malakoplakia of the prostate is a rarely reported granulomatous inflammatory disorder which may clinically mimic carcinoma of the prostate gland. A case of a 70-year-old man, with long follow-up, is reported. Histologic diagnosis allows for effective antibiotic treatment. PMID- 1889971 TI - Effects of ethinyl oestradiol/polyoestradiol phosphate and estramustine phosphate on some proteins related to haemostasis in prostatic carcinoma patients. AB - Twenty-four previously untreated patients with carcinoma of the prostate were prospectively randomized to one of the following treatments: (1) ethinyl oestradiol combined with polyoestradiol phosphate (EE/EP); (2) estramustine phosphate (EM); (3) bilateral orchiectomy. The effects on some plasma proteins related to haemostasis were studied by measuring the concentrations of alpha-1 antitrypsin, orosomucoid, haptoglobin, antithrombin III, C1-inhibitor and von Willebrand's factor before and 3 months after the start of treatment. Orchiectomy induced a reduction of alpha-1-antitrypsin and haptoglobin, while the other studied proteins were unaffected. It was found that both EE/EP and EM treatment induced significant decreases of orosomucoid, haptoglobin, antithrombin III and C1-inhibitor, while the same treatment increased the plasma concentration of alpha-1-antitrypsin. None of these treatments showed any influence on the plasma concentration of the von Willebrand factor. No differences were observed between EE/EP and EM for any of the studied proteins, suggesting comparable oestrogenic effects of these forms of treatment in patients with prostatic carcinoma. The findings are discussed in relation to the proposed difference in thromboembolic complications between EE/EP and EM treatments of prostatic carcinoma patients. PMID- 1889973 TI - Removal of silicon, aluminum and beta 2-microglobulin in chronic haemodialysis patients. AB - One hundred outpatients on chronic haemodialysis with polymethylmethacrylate (PMMA) membrane dialyzer were randomly chosen. A control group of 100 likewise randomly chosen outpatients were treated with cuprophane membrane dialyzer. In both groups the treatments lasted for one year. Comparison of the test results revealed that Si, Al and beta 2-M.G levels could be reduced in patients on chronic HD with PMMA. PMID- 1889975 TI - Neural processing of craniovascular pain: a synthesis of the central structures involved in migraine. AB - In order to determine the anatomical distribution of cells concerned with relaying craniovascular nociception, local cerebral glucose utilization was determined by the 2-deoxyglucose method in tissue autoradiographs of the alpha chloralose anesthetized cat. The superior sagittal sinus was carefully lifted from the brain by sectioning the dura laterally and the falx inferiorly and suspending the sinus across two platinum hook electrodes for stimulation. The sinus was stimulated electrically and its effect on caudal brainstem, upper cervical spinal cord and diencephalic metabolic activity determined. Stimulation of the sinus caused increased metabolic activity in the trigeminal nucleus caudalis, in the cervical dorsal horn and in a discrete area in the dorsolateral spinal cord at the second cervical segment. Metabolic activity was also increased in the ventrobasal thalamus, specifically in the ventroposteromedial (188%) nuclear group, in the medial nucleus of the posterior complex (70%) and the intralaminar complex (49%). There was no change in the surrounding thalamus, lateral geniculate nucleus or overlying cerebral cortex. These increases in 2 deoxyglucose utilisation were blocked by bilateral trigeminal ganglion ablation. The dorsolateral area activated in the spinal cord corresponds to a hitherto unrecognised group of cells in or near the lateral cervical nucleus that may form an important relay for craniovascular nociception. Further electrophysiological studies with glass coated tungsten microelectrodes have characterised the cells in these regions of the thalamus to be responsible for relaying nociceptive information. An understanding of the connections and properties of the neurons that subserve craniovascular pain is an essential prerequisite to understanding the complex pathophysiology of migraine. PMID- 1889974 TI - Tertiary hyperparathyroidism associated with metastatic cardiac calcification in a haemodialyzed patient. AB - A 32-year-old man undergoing haemodialysis treatment for 10 years was referred to our hospital because of intractable heart failure with atrioventricular block. On the 5th hospital day he was found dead in bed. Autopsy revealed extensive metastatic calcification involving the myocardium and the cardiac conduction system, and a parathyroid adenoma with hyperplastic parathyroid glands. Retrospectively, first-degree heart block developed 14 months before death, and was subsequently associated with intraventricular conduction defect and atrioventricular block (Wenckebach type). Throughout the 3 years the patient received 1 alpha-hydroxycholecalciferol (1 alpha-OH-D3) and the calcium phosphorus product (Ca X P) exceeded 70. 1 alpha-OH-D3 should not be prescribed when patients develop an increase in Ca X P and exploration of the parathyroid glands should not be delayed if heart block presents in long-term haemodialyzed patients. PMID- 1889976 TI - Review article: migraine and pregnancy. AB - A 27-year-old woman with no family or personal history of migraine presented with headache associated with unilateral paresthesias and blurred vision. This was her first, and so far only, attack of migraine with aura and led to the diagnosis of her pregnancy and to this review. Migraine can begin for the first time with pregnancy, particularly in the first trimester. Cases of migraine with aura are the most commonly reported. Preexisting migraine usually improves with pregnancy, particularly if it was associated with menstrual migraine. Headache occurs frequently in the post-partum period, particularly in known migraineurs. Migraineurs have no increased risk of complications during pregnancy and their children have no increased incidence of birth defects. PMID- 1889977 TI - Bilateral episodic mydriasis as a migraine equivalent in childhood: a case report. AB - We report a 14-year-old girl who presented with yearly attacks of bilateral internal ophthalmoplegia, nausea and headache, since the age of nine. The episodic isolated bilateral mydriasis in this child is believed to be a migraine equivalent. PMID- 1889978 TI - Migraine and epilepsy with infantile onset and electroencephalographic findings of occipital spike-wave complexes. AB - An EEG finding of temporo-occipital or temporo-parieto-occipital spike-wave complexes, suppressed by eye opening, coexisting with classical migraine, was observed in 14 children; in 13 of these patients, seizures were present. Classical migraine, visual phenomena and seizures coexisted in different clinical patterns. PMID- 1889979 TI - Criteria for the diagnosis of migraine in clinical practice. AB - Criteria for the diagnosis of migraine have evolved from generalized descriptions to specific rules designed to ensure the selection of homogenous groups of patients for research studies. For clinical practice, the former are insufficiently specific and the latter are too complex. For care of headache patients by primary care physicians, we propose that the diagnosis of migraine without aura (common migraine) is warranted if any two of the following symptoms are present: unilateral site, throbbing quality, nausea, photophobia or phonophobia. These criteria are derived from a study comparing the features of 100 patients with migraine without aura and 100 patients with chronic daily headache. The proposed criteria for the diagnosis of migraine without aura were highly sensitive and adequately specific in discriminating groups. These simple criteria should facilitate the diagnosis of migraine by primary care physicians. PMID- 1889980 TI - Flunarizine in migraine: a minireview. AB - Flunarizine is a non-selective calcium antagonist. It distributes preferentially in the adipose tissue and passes the blood brain barrier. Numerous controlled clinical studies have established that flunarizine is efficacious in migraine prophylaxis, including double-blind studies in which the drug was compared with placebo or other antimigraine drugs. To avoid side effects a special schedule or administration is necessary. Flunarizine has no myogenic effect on smooth muscle cells of the vessles. It is said to be the only calcium antagonist able to protect brain cells against hypoxic damage. In addition, the considerable body of information which shows flunarizine capable of directly influencing the central nervous system, suggests that the drug's anti-migraine action may depend on its ability to influence central phenomena. PMID- 1889981 TI - Visual evoked potentials and background EEG activity in migraine. AB - To investigate whether quantification of the background EEG during a visual evoked potential (VEP) study is of value for the diagnosis of migraine we studied 8 unmedicated migraineurs between attacks, and 10 age-matched controls. Three paradigms were used: the first two concerned pattern-reversal VEPs with different analysis times (500 and 1500 ms), and in the third paradigm the pattern did not reverse. Power spectra were calculated for individual responses, and the delta, theta, alpha and beta areas of the averaged spectra were noted as indicators of background reactivity. Alpha and beta powers were consistently but not significantly higher in the migraine group. The difference was too small to be of value as a diagnostic test. Alpha power was (not significantly) lower in the presence of photic stimulation than in its absence. As this was the case in both groups photic stimulation does not explain the higher alpha powers in the migraine group. We conclude that EEG background activity during the VEP does not distinguish reliably between migraineurs and controls. PMID- 1889982 TI - An unusual angiographic picture in status migrainosus. AB - Arteriographic findings suggestive of inflammation are described in a 26-year-old woman presenting with headache and syncope. There were no clinical findings of angitis, and a diagnosis of status migrainosus was eventually made. We present her case, as well as a review of previous cases of arterial changes in patients with headache. Most previous cases report arterial narrowing, felt to reflect spasm, whereas our patient demonstrated segmental stenoses and dilatations, perhaps implicating inflammation. The inflammatory process has been postulated as the pathogenesis of migraine pain. As most migraineurs do not undergo arteriography, the incidence of arterial change in these patients is unknown. This finding has therapeutic implications for selecting the optimal anti-migraine agent. PMID- 1889983 TI - Shortlasting, unilateral, neuralgiform headache attacks with conjunctival injection, tearing, and subclinical forehead sweating ("Sunct" syndrome): II. Changes in heart rate and arterial blood pressure during pain paroxysms. AB - The recently described "Sunct" syndrome is a rare picture of unilateral, shortlasting headache attacks accompanied by autonomic phenomena (conjunctival injection, tearing, etc.) on the symptomatic side. Heart rate and blood pressure were monitored in two elderly "Sunct" patients during and outside headache attacks. An ultrasound Doppler servo method was used for the non-invasive, continuous, beat-to-beat determination of instantaneous arterial blood pressure. In a third patient, systolic and diastolic blood pressure, both outside and during pain paroxysms, were assessed using the standard Korotkoff method. Heart rate was found to be significantly decreased during pain paroxysms. Systolic blood pressure was observed to be significantly increased during attacks, when compared with the inter-attack period, while a less consistent pattern was observed for diastolic blood pressure. Some of the changes in the cardiovascular system seemed to start prior to pain onset. Therefore, it seems unlikely that these changes were caused by pain activation of the sympathetic nervous system or the oculocardiac reflex. PMID- 1889984 TI - Changes in neutrophil met-enkephalin containing peptides in episodic cluster headache. AB - We have previously demonstrated an increase in plasma met-enkephalin levels during the pain attacks in episodic cluster headache. The present study was undertaken in order to clarify the source of the plasma met-enkephalin increase. Recent evidence has shown that peripheral blood polymorphonuclear cells contain peptides derived from the proenkephalin A system, which can be released by specific stimuli. We studied neutrophil met-enkephalin containing peptides (NMECP) in 27 episodic cluster headache patients: 24 in a cluster period (6 of them during a pain attack), and 3 in the remission period. Neutrophil met enkephalin containing peptide levels (after sequential enzymatic digestion with trypsin and carboxypeptidase B) were determined by radioimmunoassay with specific antiserum. Neutrophil peptide concentration (pmol/mg prot) was lower (p less than 0.01) in patients during the pain attack (14.4 +/- 0.36) than after their pain had subsided (36.7 +/- 0.31) and lower than in the remission period patients (35.8 +/- 0.4). We conclude that neutrophil met-enkephalin containing peptides decrease during pain in episodic cluster headache, and that they may be involved in the concomitant plasma met-enkephalin increase. PMID- 1889985 TI - Blood leukotrienes in headache: correlation with platelet activity. AB - Platelet hyperactivity, one of the commonest findings associated with migraine, has been related to increased release of biologically active substances such as catecholamines and arachidonic acid metabolites, which seem to play a role in the pathogenesis of migraine. In this study, in vitro platelet aggregation tests were performed on samples from patients with different types of headache. The presence of platelet hyperactivity was clearly demonstrated in 11 patients with classical migraine between attacks, but not in 4 patients between attacks of common migraine. Nevertheless, the presence of a marked platelet hyporesponsivity was found during the attack phase of both classical and common migraine. No difference in platelet aggregability was found between attack and post-attack phases in 5 patients with cluster headache. Blood leukotrienes were analyzed in 8 patients with classical migraine and in the 5 patients with cluster headache. During the attack phase of classical migraine both LTC4 and LTB4 were present in the peripheral blood, while the post-attack phase was characterized by the disappearance of LTC4 and the presence of LTB4 and its transisomer delta 6-trans LTB4. Blood leukotrienes were constantly absent during both phases of cluster headache. Incubation of normal platelets with LTC4 or delta 6-trans-LTB4 was followed by inhibition of platelet response to epinephrine. delta 6-trans-LTB4, at higher concentrations, induced the opposite effect. A possible role of blood leukotrienes in the changes occurring in platelet aggregability during the different phases of classical migraine, is discussed. PMID- 1889986 TI - Headache syndromes in Sierra Leone, West Africa. PMID- 1889987 TI - [Simultaneous removal of liver and pancreas does not have an effect on results of transplantation of these organs]. AB - In a retrospective clinical study we compared the outcome after pancreas and liver transplantation when both organs were retrieved from the same donor to the outcome when only one or the other organ was retrieved. The results in this article demonstrate that simultaneous procurement of liver and pancreas grafts has no detrimental effect on the rate of technical failures, or allograft or patient survival after either pancreas or liver transplantation. PMID- 1889988 TI - [Orthotopic liver transplantation at the Island Hospital. Initial experiences 1985-1990]. AB - Between 1985 and 1990 22 orthotopic liver transplantations (OLT) were realized in 19 patients. Active infection and diffuse splanchnic venous thrombosis were the only contra-indications to the intervention. Sixteen patients were transplanted electively; three had to be retransplanted urgently. Three patients had an urgent primary transplant. The incidence of surgical complications related to liver implantation was fair. One patient (5%) developed a late portal vein thrombosis; another patient (5%) had to be retransplanted because of hepatic artery thrombosis. All patients presented one or more major postoperative complications. All, but one, patients had a rejection of the allograft; five of them needed treatment with mono- or polyclonal antilymphocytic sera to reverse the rejection. One patient was retransplanted because of a hyperacute rejection. The six-month survival in this series is 68.5% (13 of 18 patients); one patient died 7 months post-OLT due to a neurological complication of her Wilson disease. Quality of life (from 6 to 64 months post-OLT) is excellent in the 12 long-term survivors. This small experience of the Bernese transplantation program shows that liver transplantation is a safe surgical procedure allowing excellent quality of life in a majority of patients. PMID- 1889989 TI - [Quality of life after liver transplantation. Preliminary catamnestic study of 8 adult patients at 1 year following liver transplantation]. PMID- 1889990 TI - [Blood transfusion and reducing the need for blood in heart transplantation]. AB - Viral infections transmitted by the donor organ or by blood and blood products are severe complications in heart transplantation. The use of blood and blood saving management is evaluated in 57 consecutive orthotopic heart transplantations. Indication was cardiomyopathy in 63%, coronary artery disease in 30%, valve disease in 5%, congenital in 5%, arrhythmia in 5% and primary cardiac malignancy in 2%. Previous open heart surgery was performed in 32%, and 81% had anticoagulation, with a mean quick value of 0.28 +/- 0.13. The total use of blood and blood products was 1151 units and was distributed as follows: whole blood and packed cells 41%, platelets 17%, fresh frozen plasma (FFP) and coagulation factors 36%, albumine 7%. Anticoagulated recipients received more FFP and factors, 7.9 +/- 5.7 U vs. 4.4 +/- 4.8 U. In the reoperation group 78% vs. 22% (p less than 0.001) in the primary operation group received platelets. Hemodilution to hematocrit 0.24 instead of 0.30 lead to a decrease of red cell transfusions per patient from 12.3 +/- 6.7 U to 6.3 +/- 7.4 U (p less than 0.001) and the percentage of patients receiving red cells was reduced from 100% to 82%. Intraoperative hemofiltration was performed in 49% (mean filtration volume was 1652 +/- 910 ml). No differences in the amount of blood and blood products could be shown. Heart transplantation is an operation with a high need for blood and blood products. Reoperation and anticoagulation are predictors for a higher use of platelets, FFP and coagulation factors. Hemodilution reduces the use of red cells, whereas intraoperative hemofiltration has no influence on the use of blood. PMID- 1889991 TI - [Surgical diseases in advanced age]. AB - Between 1982 and 1989 hospitalized treatment was applied to 615 patients aged between 85 and 101 years. The average age was 88.8 years. Operations were performed on 406 of them (66.1%). The surgical lethality amounted 16.5%. The lethality in conjunction with emergency operation was as high as 30.8% or as low as 10.7% in the context of elective operations. X-ray findings recorded from heart and lung as well as ECG provided reliable criteria for assessment of the surgical risk. PMID- 1889993 TI - [Predictive factors of postoperative infection. Value of cutaneous immunologic tests]. AB - A prospective study of the risk of postoperative local and general infectious complications was realized on 93 patients undergoing elective general surgery. The factors usually known to favour these septic complications, such as the length, the importance of the operation, as well as a preoperative loss of weight and thoracic or abdominal surgery are significantly demonstrated. Preoperative laboratory results bring no significant predictive information. On the contrary, when the immune defense mechanisms (determined by the cutaneous sensibility to ubiquitous antigens) were absent or very low before surgery, these patients significantly developed more septic postoperative complications. PMID- 1889992 TI - [Surgical intensive care in advanced age]. AB - The question of sense and limits of intensive care in the critically ill or traumatized elderly induced us to analyse our own patients. In 1986, 877 patients were treated in our surgical intensive care unit. 164 (= 19%) of these patients were greater than or equal to 70 years old. Of these 22 had suffered a trauma, 142 were non-traumatized patients. 83 had an emergency operation, 76 an elective operation, and 5 were treated conservatively. Preoperative risk assessment was estimated, according to ASA classification. The median length of stay in the surgical intensive care unit was 2.9 days for all 877 patients, that of our patients greater than or equal to 70 years 1.9 days. Mortality in the intensive care unit was 6.5% for the whole group, and 6.1% for the group greater than or equal to 70 years of age. 79 of the 164 elderly patients (= 48%) could be discharged to their homes, 52 (= 32%) into another hospital, 4 (= 2.4%) were transferred to a nursing home, and 29 (= 17.7%) died during hospitalization. Two years after admission in the intensive care unit 84 (= 51%) patients were still alive. These patients looked rather optimistically on their state of health and independence, which allows certain conclusing on an acceptable quality of life. The results seem to justify an aggressive attitude regarding primary treatment of elderly patients, all the more since in the elderly feasibility of treating quite often becomes evident only after an attempt for treatment. PMID- 1889994 TI - [Role of the A2 hospital in general surgery training in Switzerland]. AB - A full training in general surgery is difficult to achieve and involves an important professional commitment. In Switzerland, surgical theoretical and operative knowledge is mainly acquired in University Hospitals (A1 hospitals). A2 hospitals (smaller teaching hospitals) can be the best complement for this training. In these departments, general surgeons have a broad field of activity, including gastrointestinal, chest, vascular, outpatient surgery, conservative treatment and internal fixation of fractures and, sometimes, surgical endoscopy. Operative activity is intense. These departments thus allow privileged teaching positions for surgical residents and chief residents. PMID- 1889995 TI - [Modified postoperative prevention of recurrence in euthyroid struma nodosa]. AB - In a prospective clinical study after uni- or bilateral subtotal thyreoidectomy, cause of euthyreote goitre, no substitution with L-thyroxin was ordered postoperatively. The follow-up after three months and one year shows a representative time for judgement of the hormonal situation after three months. Over one year 55% with bilateral resection need hormone substitution but only 4% with unilateral. Bilateral subtotal thyroid resection seems to be a too extensive resection to leave enough functional thyroid tissue for a physiological function. PMID- 1889996 TI - [Missed and iatrogenic nerve lesions in surgery]. AB - Missed and iatrogenic nerve lesions are not encountered very often. Nevertheless, they represent an increasingly important subject because of their implications for the patient and the physician and their legal aspects. We present an overview of the patients with missed or iatrogenic nerve lesion treated at the Division for Plastic and Reconstructive Surgery of the Inselspital in Berne from 1980 to 1989. After a look at the legal aspects a few typical lesions and their treatments are illustrated. The diagnosis of a missed or iatrogenic nerve lesion differs in no way from that in other nerve lesions. Therefore, we favor an early surgical revision in all cases where the possibility of a transsected nerve must be suspected postoperatively. PMID- 1889997 TI - [Choledochal cyst as an unexpected intraoperative finding]. AB - In adulthood, choledochal cysts often surprisingly are discovered during cholecystectomy. Abdominal ultrasonography incorrectly identified the cyst as a dilated or septated gallbladder. Once suspected preoperatively, confirmation of the diagnosis is obtained by ultrasonography or computerized axial tomography, which define its relationship to the vascular structures in the porta. The rapidity and accuracy of ultrasonography favour its use as the initial investigative procedure. Direct cholangiography is the preferred modality for accurate definition of the type of choledochal cyst, ductal strictures, intrahepatic ductal configuration, and polypoid filling defects suggesting cholangiocarcinoma. The well known risk of development of ascending cholangitis as well as cystic cancer, mainly in the adult, indicates the excisional operation for preventing these complications. Cyst excision and Roux-en-Y hepaticojejunostomy is the definitive treatment of choice. PMID- 1889998 TI - [Epidemiology of liver injuries in 14 district, urban, regional and canton hospitals in Switzerland]. AB - 224 patients with liver injuries treated in 14 District and Regional Hospitals over a 10-year period were retrospectively evaluated. The results were compared to those obtained in 175 patients referred to the Central University Clinic "Inselspital", Berne/Switzerland. In all cases the degree of multiple trauma was assessed by the Injury Severity Score (ISS) and the severity of the liver injury by a Liver Injury Score (modified after MOORE). Blunt injury to the abdomen as a result of road traffic accidents, accidents at work or sporting misadventures were responsible for about 80% of all liver injuries. Peritoneal lavage was the main special investigation and was reliable in the diagnosis of haemoperitoneum. Abdominal ultrasonography proved of additional value. It allowed in experienced hands not only the diagnosis of liver injury but also some assessment of the severity of injury. Additional injuries to other abdominal organs can be assessed. By utilizing abdominal ultrasonography (or computed-tomography) liver trauma were managed conservatively in selected stable patients with minor injuries. The overall mortality was 17% in the 224 patients and compares well with the international figures. The results of treatment revealed a low mortality for liver injuries Grades I to III, whether managed in a District or Regional Hospital or in the Central University Clinic. For more severe injuries (Grades IV or V) the prognosis was worse in the District or Regional Hospitals than in the Central University Clinic. 20% of patients with liver injury Grades I to III in stable circulatory condition could be treated conservatively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1889999 TI - [Ultra-pressurized hydrodynamics in surgery]. AB - Like the CO2-laser, a H2O-jet stream may produce a selective cutting effect by working at distance. Because of the innovative possibility to add any kind of pharmacological agents to the ejected operating liquid, the new surgical equipment: Aquatom NTS-1000 allows a deep penetration of efficient medicaments directly into pathological areas, such as met in septic cutaneous diseases. PMID- 1890001 TI - [Is cecostomy still current for emergency relief of the colon?]. AB - The policy of treatment in patients with acute obstruction of the left colon remains controversial. One-stage emergency colectomy and primary anastomosis is usually recommended. Is a multiple-stage approach with primary blowhole cecostomy still a valuable solution? This retrospective analysis of 117 patients with emergency cecostomies shows an overall perioperative mortality and morbidity which are favourable compared with those reported in series of similar cases treated by one-stage procedures. In all patients the colon obstruction was treated effectively by the cecostomy. Only two of the stoma-related complications required operative intervention. The second operation was performed after a mean interval of 12 days. The low perioperative mortality of 2.1% shows, that the time was successfully used to optimize the perioperative conditions. It is concluded that patients with a very poor risk may profit by preliminary decompression by blowhole cecostomy. PMID- 1890000 TI - [Emergency hospitalization for acute, non-accidental abdominal pain. Prospective data of a surgical university clinic]. AB - During a 19-month period 549 patients (278 women, 271 men) suffering from abdominal pain unrelated to trauma (mean age 48.2 years) entered the emergency room of the Department of Surgery of the University Hospital Zurich. 43% presented during business hours, whereas 57% were admitted during nighttime and/or weekends. Clinical examination, abdominal roentgenograms (upright and supine) as well as sonography were the most commonly used diagnostic tools. 40% suffered from abdominal pain of unknown cause. The most common diagnosis on admission was appendicitis. Only half of these cases really proved to be an appendicitis. In 36% the diagnosis on admission corresponds both to the initial diagnosis made by a member of staff during his first visit, as well as to the final diagnosis. The initial diagnosis agrees in 57% with the final diagnosis. In 10% of the patients the cause of pain was not elucidated despite extensive diagnostic procedures. High technology and sophisticated diagnostics are less important than the clinical evaluation. The decision between operative or nonoperative treatment was mainly based on clinical findings. PMID- 1890002 TI - [Results of fundoplication in reflux esophagitis]. AB - A retrospective study of 71 patients treated with Nissen-Rossetti fundoplication for a symptomatic esophagitis shows that 82% of the patients are satisfied and symptom-free 2 1/2 years after surgery. 18% have recurrent reflux disease, 15% need medicamentous therapy to control their symptoms, 3% were reoperated on. Possible explantation for recurrent reflux disease are wrap dislocation and wrap disrupture. With one exception recurrences occurred within the first 12 months after operation. PMID- 1890003 TI - Chronic myelogenous leukemia: molecule to man. AB - Chronic myelogenous leukemia (CML) is the best understood human cancer. The molecular basis of CML involves activation of a cellular proto-oncogene--ABL. The consequence is to increase tyrosine kinase activity. This results in a marked clonal increase in the myeloid mass. Later on, cellular maturation is blocked and the decrease eventuates in acute leukemia. Abnormalities of other proto-oncogenes or antioncogenes, like P53, may be involved in leukemia progression. Treatment of CML involves chemotherapy and, more recently, interferon. Whether this treatment prolongs survival or increases the likelihood of cure is unknown but either result seems unlikely. Bone marrow transplants which cure about 50% of persons with CML are most effective when performed in chronic phase. PMID- 1890004 TI - Application of the polymerase chain reaction for detection of minimal residual disease of hematologic malignancies. AB - Current induction therapies for acute and chronic leukemias and the lymphomas have achieved significant complete remission rates. Despite this initial success, disease recurrence remains a major problem. Relapse from clinically undetectable residual malignant cells is the most likely mechanism of recurrence. Of crucial importance to the clinician is the accurate detection of residual malignant cells prior to clinical relapse. Standard approaches to evaluate for this minimal residual disease (MRD) allow detection only when the malignant clone exceeds 1%. Patients in remission, however, may frequently have residual neoplastic cells that are far below this level. Recently, several investigators have adapted the polymerase chain reaction (PCR) to detect tumor-specific DNA or RNA sequences. This approach is highly sensitive (able to detect 1 malignant cell in 10(6) normal cells). The application of this technique to the study of MRD thus far has been limited to tumors in which specific DNA or RNA sequence data are available. This review describes the application of PCR to the detection of MRD in patients with chronic myelogenous leukemia, acute lymphoblastic leukemia, and follicular small cleaved cell lymphoma. Because the number of clinical studies and length of follow-up is limited, detection of MRD by PCR is at present largely a research tool and the biological significance of MRD as determined by PCR must await further studies. PMID- 1890005 TI - Assessment of methylprednisolone purging efficacy on Daudi burkitt lymphoma cells from normal bone marrow. AB - Studies on normal bone marrow and Daudi Burkitt lymphoma cells were performed to determine the efficacy of selective, in vitro chemopurging with methylprednisolone (MP). We found that MP reduces the number of lymphoma cells without significant damage to bone marrow cells. This information is important because we need to improve the existing in vitro purging regimens used to cleanse autologous marrows of metastatic disease before transplantation into cancer patients who have received high-dose chemotherapy. Normal human bone marrow (NBM) and Daudi lymphoma cells were treated in parallel with various purging regimens, NBM death was evaluated using soft-agar culture, while Daudi cell death was evaluated using one-week liquid culture. A protocol of 2.0 mg/mL of MP for four hours demonstrated optimal selectivity. When treatment was followed by cryopreservation, a 1.7 log purge of Daudi cells was increased to 2.3 logs while preserving 36% of committed NBM precursors. We repeated these experiments on a simulated contaminated marrow to model closely the mixture of normal and malignant cells found in advanced, metastatic disease. We evaluated this mixed system by flow cytometric immunoanalysis using the two-color CD10/CD20 markers to detect residual, viable Daudi cells. Our initial results were reproducible in this mixed-cell system, further supporting the evidence for effective in vitro purging of bone marrow using MP. PMID- 1890007 TI - Antimicrobial chemotherapy in the intensive care unit. PMID- 1890006 TI - Porcine bioprosthetic aortic valve endocarditis with ring abscess and aortic stenosis. AB - Porcine bioprosthetic valve endocarditis is an infrequent but serious complication of valve replacement surgery. Ring (or annular) abscess is a frequent finding in mechanical valve endocarditis. In contrast, porcine valve endocarditis most often involves the cusps, and annular infection is uncommon. Porcine valvular dysfunction secondary to endocarditis usually takes the form of incompetence, whereas stenosis is less frequent. We report a case of a 76-year old female who developed endocarditis with Staphylococcus epidermidis nine months after placement of a Carpenter-Edwards porcine aortic valve. Her initial presentation included complete heart block and moderate aortic stenosis. Transesophageal echocardiography aided the diagnosis by demonstrating large vegetations, while transthoracic echocardiography showed only slight thickening of the valve leaflets. At operation, there was a circumferential abscess around the sewing ring causing valve dehiscence and virtual discontinuity of the aorta from left ventricle. Valve degeneration and organisms within the cusps were observed on microscopy. This case illustrates two infrequent complications of porcine aortic valve endocarditis, namely massive annular abscess with invasion of the conducting system and aortic stenosis. It also demonstrates the utility and limitations of transesophageal echocardiography in the diagnosis of this disorder. PMID- 1890008 TI - Capsaicin: a therapeutic option for painful diabetic neuropathy. AB - Fifteen patients with diabetes mellitus who had painful diabetic neuropathy (PDN) were enrolled in a double-blind study to test the safety and efficacy of capsaicin 0.075% (Axsain, Genderm, Northbrook, IL). Twelve of the 15 patients completed the eight-week study. Nine of the 12 patients reported symptomatic relief; of these nine, five used the drug and four used the vehicle. The three patients who reported no relief of symptoms applied the vehicle. Capsaicin is potentially effective when burning pain is a major symptom of PDN. The side effects of capsaicin were limited and minimal. This agent should be considered by clinicians for treatment of PDN. PMID- 1890009 TI - The department of surgery and the Halsted tradition. PMID- 1890010 TI - Hospice care: an overview. PMID- 1890011 TI - Management of terminal illness: the hospice concept of care. PMID- 1890012 TI - Predicting survival in the advanced cancer patient. PMID- 1890013 TI - Caring for the terminally ill: communicating with patients and family. AB - Caring for terminally ill patients requires effective communication skills. It is important that medical personnel understand appropriate ways to communicate with the patient in order to inform him about his illness, throughout its duration. Physicians must develop an understanding of how patients communicate and ways to respond to that communication. Furthermore, the physician needs to communicate with the family of the terminally ill patient. Effective communication must become a regular part of the treatment. PMID- 1890014 TI - Quality of life: what does it mean? PMID- 1890015 TI - Current issues in the leukemias. PMID- 1890016 TI - Complete nucleotide sequence of a genomic clone encoding HLA-B35 isolated from a Caucasian individual of Hispanic origin. Identification of a new variant of HLA B35. AB - The primary structure of an HLA class I genomic clone isolated from a homozygous HLA-B35 Caucasian individual of hispanic origin was determined. The nucleotide sequence of exons 1, 2, 4, 5, 6, and 7 is identical to that of the HLA-B35 allele of Oriental origin reported previously. Exon 3 differs in only three nucleotides present in a stretch of 23 bp. These changes introduce three amino acid substitutions in residues 109 (Leu----Phe), 114 (Asp----Asn), and 116 (Ser--- Tyr), two of which (114 and 116) are located in one of the beta sheets at the bottom of the peptide binding site. The nature of these replacements in this HLA B35 variant is likely to affect peptide binding and recognition by T lymphocytes. Introns 1, 2, 3, 4, 5, and 6 from this genomic clone are identical to those present in HLA-Bw58, further confirming the evolutionary origin of HLA-B35. PMID- 1890017 TI - A new HLA-DR2 extended haplotype is involved in insulin-dependent diabetes mellitus susceptibility. AB - To ascertain why HLA-DR2 seems to confer only a moderate resistance to insulin dependent diabetes mellitus (IDDM) in the high-incidence population of Sardinia, Italy, 32 families having one individual affected with IDDM (the proband) and 31 families without IDDM history were randomly selected from the same geographical area and serologically and molecularly HLA typed. The 64 haplotypes of the probands were then compared with the 122 haplotypes determined in the parents from the control families. Two haplotypes were found to have the highest percentage in the general population (12.3% and 7.3%, respectively). The first is the already described "Sardinian" extended haplotype A30, Cw5, B18, 3F130, DR3, DRw52, DQw2 (39.0% in IDDM patients). The second is an extended haplotype that has not been identified before (A2, Cw7, B17, 3F31, DR2, DQw1), and, due to the DR2 allele, we expected it to be decreased in IDDM. However, a stratified analysis performed by removing the DR3 and DR4 haplotypes showed that the frequency of this haplotype is significantly increased in IDDM patients. A peculiar feature of this haplotype is its DQw1 allele, which is DQB1*0502 and has serine in position 57 of the DQ beta chain. The absence of an aspartic acid in this position seems to confer susceptibility to IDDM and not resistance. The fact that DQB1*0502 was present in 75% of the Sardinian DR2 haplotypes may explain why, in Sardinia, DR2 is not providing the commonly recognized resistance to IDDM. PMID- 1890018 TI - Negative signal transmission through class II molecules on activated T cells. AB - Major histocompatibility complex class II antigens are expressed on human T cells following activation, but their functional role remains obscure. We have investigated the effect of anti-class II monoclonal antibodies on T cell proliferation. Our results indicated that antibodies directed against either DR, DQ, or DP were able to decrease 3H-TdR uptake if the cells had been activated by interleukin-2 (IL-2). On the other hand, minimal inhibition resulted when phorbol dibutyrate, a phorbol ester, and ionomycin, a calcium ionophore, were used to activate cells. The specificity of the effect was demonstrated by the observation that anti-class I antibodies inhibited proliferation stimulated by IL-2 and phorbol dibutyrate and ionomycin equally well. Proliferation by the anti-class II monoclonal antibodies was inhibited regardless of whether the monoclonal antibodies were added at the initiation of culture or to actively proliferating cells, suggesting that an early event was not specifically targeted. Our findings are consistent with the interpretation that class II antigens are involved in the transmission of signals to activated T cells. PMID- 1890020 TI - Nomenclature for factors of the HLA system, 1990. PMID- 1890019 TI - A physical linkage map of HLA-A, -G, -7.5p, and -F. AB - The class I region of the human leukocyte antigen (HLA) complex includes genes encoding the classical transplantation antigens (HLA-A, -B, -C), at least three nonclassical class I genes (HLA-E, -F, and -G), and many class I pseudogenes (including HLA-7.5p). We have used probes from DNA within or flanking the HLA -A, -F, -G, and -7.5p genes to construct a physical linkage map that places the HLA F, -G, and -7.5p loci in order with respect to HLA-A. The map was constructed using clamped homogeneous electric field pulsed-field gel electrophoresis. DNA was isolated from LCL 721 (A1:B8, A2:B5), a human Epstein-Barr virus-transformed lymphoblastoid cell line (LCL), and from two gamma-irradiation-induced mutants of LCL 721 lacking complementary class I haplotypes. The physical linkage data place HLA-G closest to HLA-A and place HLA-7.5p between HLA-G and HLA-F. The map constructed supports a maximum distance of 490 kilobases between HLA-A and HLA-F. PMID- 1890022 TI - Proceedings of the American Society for Therapeutic Radiology and Oncology 33rd annual meeting. November 4-8, 1991, Washington, D.C. Abstracts. PMID- 1890021 TI - HLA class I nucleotide sequences, 1991. PMID- 1890023 TI - Woodward center equipped with tools for building veterinary trends ... and its equine hospital is setting the pace. PMID- 1890025 TI - My life in our country of freedom. PMID- 1890024 TI - CVM's human drug-use policy creates additional dilemmas for veterinarians. PMID- 1890026 TI - Portable veterinary x-ray support systems for field use. PMID- 1890027 TI - Costs associated with selected preventive practices and with episodes of clinical mastitis in nine herds with low somatic cell counts. AB - Nine dairy herds (mean size, 149 cows) with bulk-tank milk somatic cell counts of less than 300,000 cells/ml and greater than 80% of cows with Dairy Herd Improvement Association linear somatic cell counts less than or equal to 4 were selected for study. Each herd was monitored for 12 consecutive months. Duplicate quarter-milk specimens were collected from each cow for bacteriologic culturing at beginning of lactation, cessation of lactation, and at the time of each clinical episode of mastitis. Streptococcus agalactiae was never isolated and Staphylococcus aureus was isolated from less than 1% of all quarters. There were 554 episodes of clinical mastitis. During the year of study, the incidence rate of clinical mastitis varied from 15.6 to 63.7% of cows among the 9 herds. Mean costs per cow per year in herd for mastitis prevention were: $10 for paper towels, $3 for nonlactating cow treatment, and $10 for teat disinfectants. Mean cost associated with clinical mastitis was $107/episode. Approximately 84% ($90) of the costs attributed to a clinical episode were associated with decreased milk production and nonsalable milk. Costs of medication and professional veterinary fees per clinical episode varied significantly among the 9 herds. Three of the herds did not have a veterinarian treat a clinical episode of mastitis during the year of study even though 2 of these herds had the first and third highest incidence rates of clinical mastitis. When calculated on a per cow in herd basis, mean costs of $40/cow/year were attributed to clinical mastitis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1890028 TI - Joining forces for research, teaching, service. PMID- 1890029 TI - Followership and leadership: promoting unity in the veterinary profession. PMID- 1890030 TI - The human/animal bond: a time for commitment. PMID- 1890031 TI - Evaluation of twelve-hour preprandial and two-hour postprandial serum bile acids concentrations for diagnosis of hepatobiliary disease in dogs. AB - In samples collected from 170 dogs suspected of having hepatobiliary disease, preprandial serum bile acids (PRSBA) and postprandial serum bile acids (POSBA) concentrations were measured, using a spectrophotometric enzymatic method. Dogs were assigned to 8 disease groups and 1 control group on the basis of hepatic histopathologic findings. Pre- and postprandial SBA concentrations and results of routine biochemical analyses (including total bilirubin, albumin, and BUN concentrations, and serum alkaline phosphatase (ALP), alanine transaminase (ALT), and aspartate transaminase (AST) activities) were expressed, using 4 indices: sensitivity, specificity, positive predictive value, and negative predictive value. Single tests and combinations of tests in series were evaluated. For diagnosis of hepatobiliary disease, the specificity of PRSBA was 100% at values greater than 20 mumol/L and of POSBA was 100% at values greater than 25 mumol/L. Test combinations with the best sensitivity for diagnosing the following diseases were: PRSBA-POSBA for cirrhosis, portosystemic vascular anomaly, and glucocorticoid hepatopathy; PRSBA-POSBA or PRSBA-ALP for cholestasis; PRSBA-POSBA or ALT-AST for chronic hepatitis; PRSBA-ALT for hepatic necrosis and passive congestion; and PRSBA-ALP for neoplasia. Test combinations with the overall highest sensitivity and positive predictive value for the fewest number of tests were PRSBA-POSBA, and either PRSBA or POSBA combined with an enzyme activity (ALT, AST, or ALP). The overall test efficacy for PRSBA vs POSBA was nearly identical: for PRSBA, it was 82.4%, and for POSBA, it was 82.3%. On the basis of the results of this study, PRSBA greater than 20 mumol/L or POSBA greater than 25 mumol/L (measured by use of an enzymatic procedure) indicates histopathologic abnormalities of the hepatobiliary system or portosystemic vascular anastomosis. Seemingly, determination of SBA concentrations can be used to indicate the propriety for hepatic biopsy. Pre- and postprandial serum bile acids concentrations should be evaluated in conjunction with routinely used hepatobiliary screening tests for best diagnostic advantage. PMID- 1890032 TI - Effect of latex and vinyl examination gloves on canine spermatozoal motility. AB - Two experiments were conducted to determine whether contact with latex or vinyl examination gloves affects canine spermatozoal motility. In experiment 1, semen was collected by digital manipulation from each of 5 dogs, and initial spermatozoal motility was assessed. The ejaculate was divided into 5 equal subsamples of 2 ml each, then randomly assigned to a control group, or treated with a 0.5-cm2 piece of latex or vinyl glove with or without talcum powder. After such exposure, spermatozoal motility was assessed at 1 and 5 minutes. Talcum powder within latex or vinyl glove treatments had no significant effect on spermatozoal motility at either period. Spermatozoal motility in samples did not differ between the control and vinyl glove groups; however, latex glove-treated samples were found to have a significant (P less than 0.05) decrease in spermatozoal motility at 1 and 5 minutes. In experiment 2, the effects of latex and vinyl gloves on canine spermatozoal motility during a sham laboratory manipulation was performed. Three ejaculates of approximately 10 ml were collected from each of 5 dogs and randomly assigned, within each dog, to be either a control (no glove exposure) or allowed to briefly contact either a latex or vinyl glove during sample manipulation. Spermatozoal motility was assessed for each sample immediately prior to and at 1 minute after manipulation. Exposure of semen to latex gloves significantly (P less than 0.05) decreased sample spermatozoal motility, whereas vinyl glove exposure had a minimal (P greater than 0.05) effect.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1890034 TI - Nonsurgical removal of a catheter embolus from the heart of a foal. AB - Nonsurgical, percutaneous, transvenous removal of a catheter fragment embolus was performed in a 14-day-old Thoroughbred foal. A basket retrieval catheter was introduced into the jugular vein and manipulated under fluoroscopic guidance to remove the fragment from the right side of the heart. Percutaneous retrieval should be considered as an alternative to thoracotomy for retrieval of intracardiac or intravascular foreign bodies. PMID- 1890033 TI - T-plate for middle carpal and carpometacarpal arthrodesis in a dog. AB - Partial arthrodesis was performed for carpal hyperextension injury in a dog. T plate application for middle carpal and carpometacarpal arthrodesis was associated with low patient morbidity and allowed normal pet activity without clinical lameness. Radiography revealed bony healing of arthrodesed joints, reactive bone formation over the dorsal aspect of the plate, and periarticular osteophyte formation. A guarded prognosis is advised for degenerative joint disease that may lead to decreased range of motion of the antebrachiocarpal joint. PMID- 1890036 TI - Renosplenic entrapment of the large colon in horses: 33 cases (1984-1989). AB - Between 1984 and 1989, 33 horses were diagnosed with renosplenic entrapment of the large colon. Duration of colic, signalment, physical findings, and laboratory values were determined, and treatment methods were evaluated. Nonsurgical correction was attempted in 22 of the horses with suspected renosplenic entrapment of the large colon and was successful in 11 cases. Survival and complication rates also were determined. Nonsurgical correction is a viable alternative to immediate surgery for renosplenic entrapment of the large colon, if cases are selected properly. PMID- 1890035 TI - Transendoscopic contact neodymium:yttrium aluminum garnet laser excision of tracheal lesions in two horses. AB - Two male racehorses (1 Standardbred, 1 Thoroughbred) were examined because of intraluminal cervical tracheal lesions, located 60 to 70 cm from the nares. A contact neodymium:yttrium aluminum garnet laser with a chisel probe attached to the fiber end was used to transendoscopically debride a nonhealing tracheal ulcer and to excise a pyogranulomatous mass. In both horses, the surgical sites healed quickly and the lesions did not redevelop. PMID- 1890038 TI - 1989 gross practice income attributable to veterinary service and product categories. PMID- 1890037 TI - Infiltrative urethral disease in female dogs: 41 cases (1980-1987). AB - Forty-one cases of infiltrative urethral disease in female dogs were reviewed. The cause was epithelial neoplasia in 29 dogs, granulomatous (chronic active) urethritis in 10 dogs, and leiomyoma in 2 dogs. Clinical signs of disease were similar in dogs with neoplastic and inflammatory disease and included strangury (36/41), hematuria (30/41), pollakiuria (20/41), vaginal discharge (16/41), and complete urinary obstruction (7/41). Results of aspiration biopsy of the urethra correlated with those of surgical biopsy in 11 of 15 dogs. In 4 of 15 dogs, results of cytologic and histologic examinations differed. Granulomatous (chronic active) urethritis is an infiltrative urethral disease in female dogs. Clinical findings are similar, but the prognosis is more favorable than that in dogs with urethral epithelial neoplasia. PMID- 1890039 TI - What is your diagnosis? Intradiskal osteomyelitis at L3 and L4, resulting in ventral extradural compression. PMID- 1890041 TI - Is social validity what we are interested in? Argument for a functional approach. AB - It is argued that neither the term social nor the term validity is best to identify the processes used or the results obtained in questioning consumers about the goals set, procedures employed, or outcomes achieved in habilitative programming. The term consumer satisfaction acknowledges the fact that it is essentially a collection of consumer opinions. The underlying intent of the process might be called habilitative validation, a name that seems to better guide our validation efforts. More important, in carefully considering consumer satisfaction assessment, it becomes clear that not only does consumer satisfaction itself need to be validated, but also that more objective methods can be used for assessing habilitative validity. However, legitimate uses still remain for consumer satisfaction measurement, as long as we do not mistake it for strong evidence of the habilitative validity of our goals, procedures, or outcomes. PMID- 1890040 TI - Social validity assessments: is current practice state of the art? AB - The use of evaluative feedback from consumers to guide program planning and evaluation is often referred to as the assessment of social validity. Differing views of its role and value in applied behavior analysis have emerged, and increasingly stereotyped assessments of social validity are becoming commonplace. This paper argues that current applications of social validity assessments are straying from the point originally proposed for them. Thus, several suggestions for improving current social validity assessment are proposed, including (a) expanding the definition of consumers to acknowledge the variety of community members able and likely to affect a program's survival, (b) increasing the psychometric rigor of social validity assessments, (c) extending assessment to heretofore underrepresented populations, (d) implementing widespread application of well-designed social validity assessments, (e) increasing meaningful consumer involvement in the planning and evaluation of behavioral programs, and (f) educating consumers to make better informed programming decisions. PMID- 1890043 TI - If reliance on epidemiology were to become epidemic, we would need to assess its social validity. PMID- 1890042 TI - Extending the concept of social validity: behavior analysis for disease prevention and health promotion. AB - A broader definition of social validity is proposed wherein a socially valid behavior-change intervention is directed to a problem of verifiable importance, the intervention is valued and used appropriately by designated target groups, and the intervention as used has sufficient behavioral impact to substantially reduce the probability of the problem's occurrence in target populations. The verifiable importance of a problem is based on epidemiological data, and the value and appropriate use of an intervention are enhanced through the use of conceptual frameworks for social marketing and behavior change and considerable formative and pilot research. Behavioral impact is assessed through efficacy and effectiveness studies. Thus, the social validity of a behavior-change intervention is established through a number of interactive, a priori steps. This approach to defining social validity is related to critical analysis and intervention issues including individual and population perspectives and "top down" and "bottom-up" approaches to intervention design. This broader definition of social validity is illustrated by a project to reduce the risk of HIV infection among adolescents. Although the various steps involved in creating socially valid interventions can be complicated, time-consuming, and expensive, following all the steps can result in interventions capable of improving a nation's health. PMID- 1890044 TI - Social validity: a note on methodology. PMID- 1890045 TI - On further development of the concept of social validity. PMID- 1890046 TI - Functional communication training to reduce challenging behavior: maintenance and application in new settings. AB - We evaluated the initial effectiveness, maintenance, and transferability of the results of functional communication training as an intervention for the challenging behaviors exhibited by 3 students. Assessment indicated that escape from academic demands was involved in the maintenance of the challenging behaviors. Social attention was also implicated as controlling the behavior of 1 student. The intervention involved teaching alternative assistance-seeking and attention-getting phrases to the students in an effort to replace challenging behavior with these verbal equivalents. Multiple baseline data collected across the 3 students indicated that not only did the intervention substantially reduce challenging behavior but also that these results transferred across new tasks, environments, and teachers, and were generally maintained from 18 to 24 months following the introduction of functional communication training. These results are discussed in light of recent efforts to develop effective interventions for severe challenging behavior and to understand the processes underlying transfer and maintenance of intervention effects. PMID- 1890047 TI - Interspersed requests: a nonaversive procedure for reducing aggression and self injury during instruction. AB - Interspersed requests are simple commands, with a high likelihood of being followed correctly, that are interspersed among instructional trials to increase the probability that a learner will attempt to perform new or difficult tasks without engaging in aggression or self-injurious behavior. This report presents two assessments of the effect of interspersed requests on aggression and self injury during instruction. The participants were individuals with severe mental retardation who used aggression and self-injury to avoid difficult instructional situations. Results from both studies indicate that interspersed requests were effective at increasing the responsiveness of the learners to instructions and reducing levels of aggression and self-injury. PMID- 1890048 TI - Establishing operations and reinforcement effects. AB - Positive reinforcement procedures have had a major impact on educational programs for the developmentally disabled; nevertheless, variation in reinforcer effectiveness both within and across individuals is a common phenomenon. This study examined one class of variables--establishing operations--that might influence the effectiveness of reinforcers. Five developmentally disabled adult males participated. Responding on one of two motor tasks--switch closure or block placement--was assessed during baseline, satiation, and deprivation conditions with respect to three classes of consequences: small food items, music, and social praise. Deprivation and satiation conditions were constructed so as not to alter significantly the normal course of events in a subject's day. For example, food deprivation entailed scheduling sessions just prior to a subject's regular lunch, and social deprivation involved limiting a subject's access to social interaction for 15 minutes, during which time the subject had access to an assortment of other activities. Results showed that each stimulus class functioned as reinforcement with different degrees of effectiveness during satiation versus deprivation conditions. These results are discussed in light of previous research on enhancement of reinforcer efficacy as well as the assessment and identification of functional reinforcers, and implications are presented for future research and client habilitation. PMID- 1890050 TI - Effects of contextual competence on social initiations. AB - The frequency of social initiations and satisfaction with interactions in three dyads, each consisting of 1 student with disabilities and 1 nondisabled peer, were assessed under two alternating conditions: Condition 1 assessed the interactions around a set of four trained computer games, and Condition 2 assessed interactions when students were playing a set of four untrained computer games. Training was conducted with a multiple baseline design across participants and was followed by social interaction probes using an alternating treatments design. The results indicated greater frequencies of social initiation by 5 of 6 participants, higher degrees of game satisfaction by all participants, and equal or higher degrees of peer satisfaction by 5 of 6 participants when playing trained games in comparison to untrained games. PMID- 1890049 TI - Constructed-response matching to sample and spelling instruction. AB - The development of interactive programmed instruction using a microcomputer as a teaching machine is described. The program applied a constructed-response matching-to-sample procedure to computer-assisted spelling instruction and review. On each trial, subjects were presented with a sample stimulus and a choice pool consisting of 10 individual letters. In initial training, sample stimuli were arrays of letters, and subjects were taught to construct identical arrays by touching the matching letters in the choice pool. After generalized constructed-response identity matching was established, pictures (line drawings) of common objects were presented as samples. At first, correct spelling was prompted by also presenting the printed name to be "copied" via identity matching; then the prompts were faded out. The program was implemented with 2 mentally retarded individuals. Assessment trials determined appropriate words for training. Correct spelling was established via the prompt-fading procedure; training trials were interspersed among baseline trials that reviewed and maintained spelling of previously learned words. As new words were learned, they were added to a cumulative baseline to generate an individualized review and practice battery for each subject. PMID- 1890051 TI - Social interactions in three supported employment options: a comparative analysis. AB - Controversy exists over the benefits that workers with severe disabilities accrue under different supported employment options. This study focused upon one benefit of supported employment: social integration. Direct observation procedures were used to assess the social interactions of 37 adults with severe disabilities in 18 employment programs representing three different supported employment contexts (individual, enclave, and work crew). Results indicated that workers employed in individual and enclave programs had significantly more contact with nondisabled persons than did members of work crews. No differences were detected in the social contact rate between disabled and nondisabled workers in individual versus enclave sites. Furthermore, few differences in type of interactions across the three different work options were revealed. Results suggest that both individual and enclave models are capable of facilitating social integration. However, characteristics of specific job sites, more so than the employment model per se, may determine whether a particular employment setting is conducive to social integration. PMID- 1890053 TI - Inducing variability in communicative gestures used by severely retarded individuals. AB - Handicapped individuals who have been taught spontaneous gesture requests often use only a small part of their vocabulary. Procedures to recover the unused part of this vocabulary have not been documented. This study was designed to identify procedures for increasing the proportion of gestures used spontaneously. Six mentally handicapped individuals served as subjects. After a baseline phase during which spontaneous gesture requests were reinforced, consequences were withheld for high-rate gesture requests. This led to an increase in different gesture requests. Although gesture requests did not return to baseline levels during a reversal condition, functional control was demonstrated by way of a multiple baseline across subjects. The absence of a reversal effect suggests enduring effects of the procedure. PMID- 1890052 TI - Facilitating conversation through self-initiated augmentative communication treatment. AB - We examined the conversational skills of 2 adult males with severe motor and speech deficits resulting from cerebral palsy. A multiple baseline design across subjects was used to determine the effectiveness of an intervention strategy designed to teach them to use an augmentative communication system (Touch Talker) independently. The dependent measure was the number of conversation initiations relative to conversation reactions during spontaneous communication across baseline and treatment. The treatment included specific training on using the augmentative system to participate in communication. Once the intervention began, the production of conversation initiations accelerated at a rapid rate. The treatment program was effective in training the subjects to use the augmentative system to increase conversation participation. These results demonstrate that training on the operation of the device alone is not sufficient to ensure improvement in conversation performance, and that it is important to incorporate direct conversational treatment when providing instruction on the use of augmentative communication systems for severely speech-impaired individuals. PMID- 1890054 TI - Functional assessment, curricular revision, and severe behavior problems. AB - An adolescent female with multiple handicaps and a long history of severely disruptive behavior participated in a functional assessment linked directly to specific revisions in her school curriculum. During Phase 1, reversal designs were used to test hypotheses pertaining to antecedent and curricular influences on problem behavior. During Phase 2, a multiple baseline across afternoon and morning time periods demonstrated that the curricular revisions were effective in eliminating severely disruptive behavior and increasing on-task responding. Data also showed that inappropriate "psychotic" speech was reduced and appropriate social interactions were increased. Follow-up results showed that the changes were maintained throughout the school year. Questionnaire data provided social validation of the procedures and outcomes. The findings are discussed in relation to their implications for functional assessment, individualized curricula, and positive programming for students with disabilities and serious behavior problems. PMID- 1890055 TI - Conventional therapy of head and neck cancer. AB - Squamous cell cancers occurring at the various sites within the head and neck are remarkable for their differences with respect to clinical presentation, staging, risk of neck disease, anatomic considerations, histology, and response to conventional therapy. In general, either surgery alone or radiation alone can be used effectively for early (T1, T2, favorable T3) tumors. If surgery can be done safely and without significant disruption of normal function or cosmesis, as in early oral cavity tumors, surgery is preferable because it avoids a prolonged and uncomfortable acute treatment and long-term radiation complications. Otherwise, as in early oropharyngeal and laryngeal tumors, radiotherapy is favored. Although single modality therapy can be given for advanced disease, combined surgery and radiotherapy appear to offer improved locoregional control and enhanced survival. The status of neck nodes is a critical prognostic factor, and the neck remains the most common site of treatment failure. Consequently, treatment of the neck can never be divorced from treatment of the primary. For early neck disease, single modality therapy suffices, but for more extensive disease, combined treatment is indicated. In view of the complexity of head and neck cancer both in terms of diagnosis and treatment, management of the patient should begin in a multidisciplinary setting in which all tumor and patient factors can be evaluated and a treatment plan agreed upon by both surgeon and radiotherapist. PMID- 1890056 TI - New concepts in head and neck surgery. AB - New methods in head and neck cancer treatment have enabled the oncologic surgeon to pursue the goals of conservation of head and neck physiologic function, reduce the morbidity and mortality associated with advanced head and neck cancers, and increase the cure rates for cancers once considered inoperable. Advances in multimodality therapy may lead in the next decade to less surgical mutilation and higher cure rates. PMID- 1890057 TI - Recent advances in radiation therapy for head and neck cancer. AB - The most efficacious treatment method for head and neck cancer is not yet defined. However, there have been some improvements made in the radiotherapy of head and neck cancer that are encouraging. Both hyperfractionated radiation therapy and accelerated radiation therapy have improved the local control rates in numerous primary sites, and the results of more rigorous prospective randomized studies, if positive, will justify more routine use of these techniques. The use of neutrons for unresectable salivary gland tumors has clearly been established as the treatment of choice. Local control as well as cosmetic outcome is excellent, with the only disadvantage being that neutron therapy is not as widely used as photon radiation. The same is true for charged particle therapy, the greatest utility of which appears to be for relatively small tumors adjacent to critical structures such as the brain and spinal cord. We also believe that intraoperative radiation therapy shows great promise and may soon be more widely available for the treatment of head and neck cancers. However, we believe that the most exciting advancement in the treatment of head and neck cancer is the use of concomitant radiation therapy and chemotherapy, a topic that is discussed in detail in another article in this issue. PMID- 1890058 TI - Roles of computed tomography and magnetic resonance imaging diagnoses in the treatment of head and neck cancer. AB - This article has provided an overview of the current imaging techniques for evaluating head and neck cancer. Advantages, disadvantages, and complementary roles of CT and MRI have been described. PMID- 1890059 TI - Chemotherapy for recurrent and metastatic head and neck cancer. AB - At the present time, the treatment of recurrent and metastatic head and neck squamous and salivary gland cancers with chemotherapy is palliative. Pain relief, improvement in functional parameters, and improved survival are important goals. Although survival benefits are small, palliation can be significant. For squamous cancers, the median duration of response to chemotherapy is 2 to 4 months, and overall survival is about 6 months. Responses can be achieved with acceptable toxicity for good palliation in approximately 30% of patients treated with the standard regimens. Although more intensive chemotherapy regimens often result in higher response rates in pilot trials, they do not offer significant gains in effectiveness or survival. In salivary gland malignancies, results are substantially better, but this may only reflect the different natural history of this heterogeneous group of tumors. A small number of patients will have excellent and very durable responses to chemotherapy. Unfortunately, at this time we are unable to select these patients or determine which regimen will produce this desired result. The optimal use of currently available drugs is in the process of refinement. The timing of palliative chemotherapy represents a major challenge to oncologists and patients. Chemotherapy may in the future have a role in the cure of patients with recurrent disease, but innovative therapy, combined modality approaches, and new drug development will all need to be investigated. We look forward toward a new understanding of tumor biology and the development of agents that may substantially improve the control of these tumors. PMID- 1890060 TI - The Wayne State University experience with adjuvant chemotherapy of head and neck cancer. AB - Because of the poor results of standard therapy in patients with locally advanced head and neck cancers, chemotherapy is increasingly used to improve the outcome of these patients. In resectable disease, chemotherapy is being investigated before definitive treatments, after surgery, concurrent with postoperative radiotherapy, after radiotherapy, and for possible laryngeal salvage. In unresectable cancers, chemotherapy before, concurrent with, and following radiotherapy is being investigated. PMID- 1890061 TI - Analysis of prognostic factors in squamous cell carcinomas of the head and neck. AB - It appears that prognostic factors of proven value in the management of other malignancies have marginal value in the treatment of patients with squamous cell carcinomas of the head and neck (SCCHN). For example, age, sex, and performance status do not correlate with treatment outcome. Similarly, histologic differentiation has little predictive value, with undifferentiated carcinomas of nasopharyngeal origin being a possible exception. On the other hand, primary tumor site may be an important prognostic factor, with tumors arising from the nasopharynx, oral cavity, and possibly the oropharynx having a more favorable outcome, whereas tumors of the hypopharynx appear to be the least favorable. A tumor's TNM stage is also highly predictive of response to treatment and survival. Overall stage of disease is an effective predictor of relapse and survival only for patients with limited disease and only after the primary site is specified. Independent of primary tumor site, an inverse correlation clearly exists between T and N stage and either response to treatment or overall survival. Flow cytometry, a relatively new test, appears to be one of the most significant predictors of response to chemotherapy, relapse, and survival in patients with SCCHN. As a prognostic factor, DNA tumor content may be independent of all other known clinical and pathologic factors. Patients with diploid tumors have a superior relapse-free and overall survival as compared with patients whose tumors are aneuploid. Another parameter of significant value is the patient's response to induction chemotherapy, with responding patients demonstrating a far superior relapse-free and overall survival compared with nonresponders. In summary, the site of the primary tumor, its T stage, N stage, and DNA content, and the magnitude of its response to induction chemotherapy are the most valuable prognostic factors in SCCHN. It is assumed, however, that as new and more effective therapies are developed for patients with SCCHN, previously significant prognostic factors will cease to have clinical or scientific value. Similarly, as new diagnostic tests and staging tools are developed, a new generation of prognostic factors with greater biologic and clinical relevance is likely to emerge. In the evolution of new therapies for patients with SCCHN, prognostic factors such as those mentioned here or ones yet to be evaluated will be central to the design of clinical studies and the identification of specific patients for specific therapies. Once treatment is initiated, treatment-related prognostic factors may further identify patients for whom modifications of the initial therapeutic plan would be appropriate.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1890062 TI - Organ preservation in multimodality therapy of head and neck cancer. AB - Several conclusions can be drawn from the studies that have been done to evaluate induction chemotherapy and organ preservation. These principles can serve as the foundation for the design of future trials for organ preservation. 1. The addition of chemotherapy to surgery/radiation for advanced head and neck cancer has not improved overall patient survival. 2. Surgery and radiation therapy can safely and effectively be given after chemotherapy to patients who have had induction chemotherapy. 3. Neoadjuvant chemotherapy followed by definitive radiation therapy can achieve laryngeal preservation in a high percentage of patients, without compromise of survival. 4. In order to change the standard of care, organ preservation trials must be conducted in a randomized, prospective fashion. 5. Organ preservation trials must be conducted for specific sites and stages of head and neck cancer. 6. All patients with nonlaryngeal head and neck cancer who are treated with induction chemotherapy for organ preservation should be treated within a protocol setting. PMID- 1890063 TI - Randomized trials of induction chemotherapy. A critical review. AB - There are nine prospective randomized trials comparing induction chemotherapy with standard therapy published in either final form or as preliminary abstract reports. Only one of the six randomized trials critiqued was designed to account for all known prognostic factors, utilized an effective chemotherapy regimen, and had excellent compliance such that the numbers of patients completing the protocol were adequate to provide a valid statistical interpretation of the data. This was the VA cooperative group trial to preserve the larynx. Although this trial did not show a difference in survival between surgically treated patients and those who received induction chemotherapy, the larynx was preserved in two thirds of patients. The results of the other published trials cannot be considered conclusive owing to the flaws in design and interpretation noted in this review. These trials do confirm the feasibility of administering chemotherapy prior to surgery and RT and do confirm the prognostic importance of various factors suggested by the results of single institution trials. Induction chemotherapy has been tested for almost two decades. During this time we have learned the importance of treating intensively to obtain a high complete response rate. At one primary site, the larynx, it has been shown that 64% of patients can be rendered histologically disease-free after three courses of cisplatin and 5 FU. The results of three randomized trials indicate that induction chemotherapy can change the expected pattern of recurrence by decreasing the rate of distant metastases. This early systemic treatment of micrometastases may also reduce the mutation rate theorized for the development of drug resistance. The goals of future randomized trials should include the use of dose-intensive multidrug regimens to increase complete response rates, improve locoregional control, and decrease distant metastases. Induction chemotherapy trials with cisplatin and 5 FU should explore organ preservation at sites other than the larynx where significant functional impairment results from standard surgical approaches. Randomized trials must be carefully designed and rigorously conducted to ensure that the results and conclusions are valid. New regimens, perhaps incorporating growth factors, need to be identified and tested in this group of patients. Finally, improvement in survival must remain a primary goal of multimodality therapy for advanced head and neck cancer. PMID- 1890064 TI - Biologic rationale of combined radiotherapy and chemotherapy. AB - This article presents a brief review of the mechanisms by which chemotherapy can be combined with radiotherapy to improve the therapeutic ratio, the possible mechanisms of interaction between chemotherapy and radiotherapy, the various factors that may influence their combined effects, and future perspectives in this area of clinical and laboratory research. PMID- 1890065 TI - Radiotherapy with concomitant chemotherapy for head and neck cancer. AB - Concomitant chemoradiotherapy has already resulted in statistically significantly improved disease-free and overall survival for patients with head and neck cancer. Although the differences observed so far have been small, it is of note that the improved outcome was achieved even though only single-agent chemotherapy was used. More recent, chemoradiotherapy schedules have employed more aggressive chemotherapy regimens, frequently with split-course radiotherapy. Several of these schedules have resulted in encouraging response and survival figures in phase II trials. At the same time, toxicities, usually in the form of mucositis, have also been increased. The role of these schedules in the management of patients with advanced head and neck cancer will need further evaluation, eventually using a randomized format comparing such a regimen with standard radiotherapy alone. Their use outside of clinical trials cannot be recommended yet. PMID- 1890066 TI - Controversies in the multimodality management of head and neck cancer. AB - A number of prospective controlled trials currently exist, with consistent results that help define the current role of chemotherapy in patients with advanced-stage head and neck cancer, and they may offer directions for future research. Neoadjuvant combination chemotherapy appears to offer no survival advantage but does appear to select a subgroup of patients who do not require surgical intervention, thereby resulting in organ preservation. Patients who have received neoadjuvant chemotherapy and obtain a prompt complete response are more likely to realize a significant local control advantage following regional therapy. Randomized studies using simultaneous chemotherapy and radiotherapy have resulted in higher clinical local control and overall survival rates. These studies have used only single agents, however. Phase II trials with drug combinations have been even more encouraging as compared with historical data. By comparing different treatment schemes, such as alternating and sequential, to simultaneous schedules, it is hoped that differences in toxicity, the role of dose-intensity, and regional control rates can be further defined. The information now exists for the formulation of well-designed, prospective randomized clinical trials comparing different schemes of concomitant chemotherapy with standard regional treatment regimens. PMID- 1890067 TI - Chemoprevention in head and neck cancer. AB - It is not a coincidence that the aerodigestive tract has proven such a fertile ground for the evaluation of chemoprevention. The incidence of second primaries and the concept of field cancerization made the need for prevention acute and showed the limitations of even the most curative of treatments. New and presumably less toxic agents are being evaluated; chemoprevention is being applied to asymptomatic populations at higher risk for lung, colon, breast, and other neoplasias. Biomarkers may be instrumental in rapid development of these new clinical applications, but much is still to be done. Yet unanswered is whether suppression of premalignant lesions will ultimately decrease cancer incidence. Survival in the second primary prevention trial has not thus far shown a significant improvement and toxicities were significant. Many questions remain in the study of chemoprevention; head and neck cancer provides a conducive model in which these answers might be found. PMID- 1890068 TI - Nasopharyngeal carcinoma. Biology, natural history, and therapeutic implications. AB - Undifferentiated carcinoma of the nasopharyngeal type (UCNT) is a particular head and neck Epstein Barr virus (EBV)-related carcinoma. It has a specific geographic repartition and a short natural history. Radiotherapy allows a high rate of local control, but 80% of patients die with or of metastatic spread. This tumor is also very chemosensitive, but the role of chemotherapy is still controversial. The Gustave Roussy experience (1984-1989) in this field is described. An 80% response rate in metastatic disease, 10% of unmaintained long-term complete responders after chemotherapy, and the achievement of 66% complete response with bleomycin epirubicin-cisplatin (BEC) regimen in locally advanced disease are the main arguments for a primary role for chemotherapy in this potentially curable disease. PMID- 1890069 TI - Fetal bovine serum and immunogenicity of rat colon cancer cells. PMID- 1890070 TI - Murine T cell leukemia line in suspension culture. PMID- 1890071 TI - Culture of human adult endothelial cells on liquid-liquid interfaces: a new approach to the study of cell-matrix interactions. AB - Human adult endothelial cells (ECs) were cultured on liquid-liquid interface formed when aqueous culture medium is overlaid onto a fluorocarbon solvent. When ECs were seeded on untreated interfaces, some cells seemed to attach but they did not spread or grow. In contrast, when ECs were seeded on interfaces pretreated with such proteins as collagen type IV (COL), laminin (LN), fibronectin (FN), and fibrinogen (FG) the cells spread and proliferated until they formed confluent monolayers. Proteins such as bovine serum albumin (BSA) or gelatin (GN) were not as effective in providing surfaces for vigorous growth. Cells grown on fluorocarbon interfaces expressed specialized characteristics exhibited by endothelial cells grown under the usual culture conditions; they grew in a cobblestone monolayer, stained positively for Factor VIII-related antigen, and produced angiotensin-converting enzyme. The growth rate of ECs was the same whether they were cultured on treated fluorocarbon interfaces or on the usual tissue culture plastic surfaces. Using this culture system, the interactions of ECs with various adhesive proteins used as substrata was examined. ECs were observed to attach readily to the interfaces coated with GN, COL, LN, FN, and FG, but poorly to those coated with BSA. All the substrates tested, with the exception of BSA, promoted EC growth on fluorocarbon interfaces; ECs tended to grow more rapidly on COL- or FG-coated interfaces than on LN-, FN-, or GN-coated interfaces. PMID- 1890072 TI - The bicarbonate ion is essential for efficient DNA synthesis by primary cultured rat hepatocytes. AB - Bicarbonate in the culture medium is essential for DNA synthesis of primary cultured rat hepatocytes stimulated by epidermal growth factor (EGF). When primary cultured hepatocytes in supplemented Leibovitz L15 medium were placed in a 100% air incubator, no increase in DNA synthesis was observed even after stimulation by EGF. However, when these cells were cultured with NaHCO3 and EGF and placed in a 5% CO2:95% air incubator, a stimulus of DNA synthesis more than 10-fold greater than in cultures in air only was seen, and many mitotic figures could be identified. Furthermore, NaHCO3 added to supplemented DMEM/F12 medium enhanced the DNA synthesis of primary cultured rat hepatocytes in this medium. The ideal pH of the medium for DNA synthesis of cultured hepatocytes was in the range of 7.6 to 8.0. A dose response of NaHCO3 in several media showed that DNA synthesis of the cells increased as the concentration of NaHCO3 increased and that 25 to 30 mM NaHCO3 in the medium was optimal for the replication of DNA by primary cultured rat hepatocytes. PMID- 1890073 TI - Effects of differentiation of embryonal carcinoma cells (P19) on mitochondrial DNA content in vitro. AB - The embryonal carcinoma cell line P19 is derived from mouse teratocarcinomas. These pluripotent cells can be induced to differentiate into a variety of cell types by exposure to various drugs. We used retinoic acid to induce embryonal carcinoma cells to differentiate into neuronlike cells. In this study, we show that changes occur in mitochondria during differentiation of embryonal carcinoma cells to neuronlike cells. We found that various morphologic parameters such as mitochondrial fractional area and mitochondrial size decrease as embryonal carcinoma cells differentiate into neuronlike cells. Similar changes were also observed in mitochondrial DNA content. Stereologic analysis of cell preparations provided a measure of mitochondrial fractional area per cell and mtDNA content was assessed by radiolabeled mtDNA probe. This study establishes that mitochondria are regulated as cells differentiate. PMID- 1890075 TI - Aerosol deposition and delivery of therapeutic aerosols. PMID- 1890074 TI - Establishment and characterization of bovine mammary epithelial cell lines. AB - One bovine mammary epithelial cell clone, designated PS-BME-Cl, and two bovine mammary epithelial cell lines, designated PS-BME-L6 and PS-BME-L7, were derived from mammary tissue of a pregnant (270 day) Holstein cow. The cells exhibit the distinctive morphologic characteristics of mammary epithelial cells and express the milk fat globule membrane protein, PAS-III. They form domes when cultured on plastic substrata and acinilike aggregates when cultured on a collagen matrix. These cells are capable of synthesizing and secreting alpha-lactalbumin and alpha s1-casein when cultured on a collagen matrix in the presence of insulin, cortisol, and prolactin. The cells have a near-normal diploid number and do not grow in suspension culture. When transplanted to the cleared mammary fat pads of female athymic nude mice, the cells readily proliferate forming noninvasive palpable spherical cellular masses within 8 wk after inoculation. The cells may become a useful tool to study the regulation of ruminant mammary epithelial cell growth and differentiation. PMID- 1890077 TI - A method of intrasegmental allergen provocation followed by bronchoalveolar lavage in patients with pollen asthma. PMID- 1890076 TI - Aerosols in the treatment of asthma. PMID- 1890078 TI - Outcomes of emergency room treatment of children with asthma. AB - Duration of symptoms, medication use and follow-up medical care were examined over an 8-week period in children following emergency room treatment for an acute asthma episode. Two groups of children were compared: Short-course (N = 90) and Continuous Medication Users (N = 46). Over a third of Short-Course Users continued to report symptoms up to 6 weeks following the index episode with 31% reporting medication use at 8 weeks. Relapse, resulting in an emergency room visit, occurred in 26% of all study children. Factors associated with relapse included maternal smoking, female gender, prior hospitalization for asthma, cough, and medication use during the follow-up period. PMID- 1890079 TI - Breathing patterns during sleep in stable asthmatic children. AB - Breathing patterns during sleep at night were studied in 15 asymptomatic asthmatic children and 11 nonasthmatic controls using impedance pneumography. Inspiratory time (TI), expiratory time (TE) and expiratory time/inspiratory time ratio (TE/TI) were used as the indices of breathing patterns. In the daytime, TI, TE and TE/TI, showed no significant differences between asthmatics and controls. During nocturnal sleep, TE and TE/TI increased significantly in the asthmatics compared with the value during daytime, while these values showed only a small variation overnight in the controls. TI showed no significant changes through the night in either the asthmatics and the controls. The results of this study indicate that the stable asthmatic children had abnormal breathing patterns during nocturnal sleep. PMID- 1890080 TI - Pulmonary function in a hospital population of asthmatic children. AB - Traditionally, assessment of control of pediatric asthma has relied on symptoms reported by the child and his or her family, and on clinical examination at office visits. A survey of the pulmonary function of 100 clinically stable asthmatic children, recruited from the outpatient clinics of the Royal Children's Hospital, Melbourne, Australia for a clinical drug trial was performed. Correlation of baseline pulmonary function with symptom scores recorded at home and home monitoring of peak expiratory flow variability (PEFV) found that a third of these clinically stable asthmatic children had an abnormal FEV1 and half had an abnormal FEF25-75; however, there was no correlation between symptom scores and FEV1 or PEFV. Objective measurements of pulmonary function are needed to ensure good asthma control. Home monitoring of peak expiratory flow can provide a valuable aid for the management of pediatric asthma. PMID- 1890081 TI - Parental smoking and the risk of childhood asthma. AB - In order to explore the correlation between parents' smoking habits and bronchial asthma in children, we undertook a cross-sectional study of 3300 (54% males, 46% females) school children aged 7-12 years old. A survey of smoking habits and attitudes conducted in Saudi Arabia showed a positive correlation between parental smoking and asthma. This study showed a significant link between parental smoking and chest wheeze or whistling, cough, and family history of rhinitis. Evidence is accumulating that there is a relationship between parental smoking and respiratory symptoms in Saudi children. The present study results are clear evidence of a definite association between smoking in the home and bronchial asthma in young children, which not only may present immediate problems, but may also be a cause of illness in the future. PMID- 1890082 TI - Individualized asthma self-management: a beginning. PMID- 1890083 TI - A case report of unilateral hyperlucent lung syndrome. PMID- 1890084 TI - Anxiety disorders of childhood and adolescence: a critical review. AB - The 1980s were a decade of advancement in the knowledge of anxiety disorders in children and adolescents; this sets the stage for research achievements in the 1990s. This review examines the anxiety disorders of childhood and adolescence (separation anxiety disorder, overanxious disorder, and avoidant disorder), including prevalence rates, demographic profiles, comparisons of clinical presentations in different developmental age groups, and comorbidity patterns. Fears and simple phobias, obsessive-compulsive disorder, post-traumatic stress disorder, and panic disorder in children and adolescents are also evaluated. The controversy of whether panic attacks occur in prepubertal children is addressed. A brief review of behavioral and pharmacological treatment studies is included. Future directions for research are suggested. PMID- 1890085 TI - Overanxious disorder: a review of its taxonomic properties. AB - The taxonomic properties of overanxious disorder are reviewed using the diagnostic criteria and other features listed in the DSM-III-R manual as a template. The data suggest that overanxious disorder is only a modestly reliable, distinct and valid taxon, and that adjustments to the diagnostic items and criteria and improved sources and methods of data capture are needed. Such changes should be on the basis of empirical data. Since these data are not yet extant, better psychometric-type studies are needed, coupled to assessments of validity. Recently, there has been a distinct increase in number and quality of studies. Although some adjustments are needed, to alter overanxious disorder too much in DSM-IV could make past studies of doubtful relevance and could force a fresh start instead of building on current knowledge. PMID- 1890086 TI - Social phobia and overanxious disorder in school-age children. AB - Epidemiological data indicate that, based on current diagnostic criteria, anxiety disorders are the most common childhood disorders. Furthermore, the comorbidity rate among the various diagnostic categories is quite high, and relatively little attention has been given to delineating the specific and distinct parameters of these disorders. The current study examined the characteristics of overanxious disorder and social phobia by comparing children who have these disorders to matched normal controls. The results indicated that children with social phobia could be differentiated from the other groups, based on self-report inventories, daily diary data, and a psychophysiological assessment. However, there were few variables that distinguished overanxious children. The results provide strong support for the diagnostic validity of social phobia in children but lesser support for overanxious disorder as currently defined. PMID- 1890087 TI - Simultaneous prepubertal onset of panic disorder, night terrors, and somnambulism. AB - Concurrent acute onset of night terrors, somnambulism, and spontaneous daytime panic attacks meeting the criteria for panic disorder is reported in a 10-year old boy with a family history of panic disorder. Both the parasomnias and the panic disorder were fully responsive to therapeutic doses of imipramine. A second case of night terrors and infrequent full symptom panic attacks is noted in another 10-year-old boy whose mother has panic disorder with agoraphobia. The clinical resemblance and reported differences between night terrors and panic attacks are described. The absence of previous reports of this comorbidity is notable. It is hypothesized that night terror disorder and panic disorder involve a similar constitutional vulnerability to dysregulation of brainstem altering systems. PMID- 1890088 TI - Risk factors for substance use among high school students: implications for prevention. AB - To identify salient risk factors for drug use that could be targeted for modification in prevention programs, a survey was administered to a sample of 1,091 urban and suburban 10th grade students. Substantial proportions of students reported alcohol alcohol and cigarette use in the past year, and around 10% reported heavy use of these substances. In general, the measured risk factors most strongly associated with the use of alcohol, cigarettes, and marijuana were those derived from the socialization model of substance use; however, certain factors derived from the stress/strain and disaffiliation models also were related to increased drug use risk. PMID- 1890089 TI - Risk factors and their relation to initiation of alcohol use among early adolescents. AB - This study examined the relationship between risk factors and initiation of alcohol use over a 15-month period among a cohort of 7th graders who were abstainers at the time of initial testing. The relationship between risk factors and alcohol use was examined using a discriminant function analysis. At the univariate level, rejection of parental authority, deviant behavior, and sensation seeking were statistically significant. The discriminant function retained only three of the risk factors: rejection of parental authority, deviant behavior, and religious commitment. Implications for school-based prevention programs are discussed, particularly the need to target primary prevention programs based upon adolescents' risk. PMID- 1890090 TI - Psychopathology among substance abusing juvenile offenders. AB - The prevalence of substance abuse and coexisting DSM-III psychiatric disorders was evaluated in 111 juvenile offenders. As expected, a high rate of conduct disorder (91%) was present in both substance abusing and nonsubstance abusing juvenile offenders. However, significantly higher rates of attention deficit disorder and aggressive subtype of conduct disorder were present in those offenders who abused drugs and alcohol (54%). Excluding all conduct and oppositional disorder diagnoses, 39% of substance abusers versus 14% of the nonsubstance abusers demonstrated comorbid psychiatric diagnoses. These findings suggest that careful psychiatric evaluation of juvenile substance abusers may be necessary to optimize treatment planning. PMID- 1890091 TI - Substance abuse prevalence and comorbidity with other psychiatric disorders among adolescents with severe emotional disturbances. AB - Among 547 adolescents with serious emotional disturbances, ages 12 to 18, this study assessed (1) prevalence of DSM-III substance use disorders (i.e., alcohol and marijuana abuse/dependence), and (2) comorbidity with DSM-III Axis I disorders. Factors of age, sex, state location, and type of treatment program also were examined. Data were analyzed by logistic regression. Significant factors (p less than 0.05) associated with severe alcohol or marijuana abuse/dependency diagnosis included (1) residential mental health treatment program, 2.37 Odds Ratio (OR); (2) conduct disorder diagnosis, 2.18 OR; (3) depression diagnosis, 1.75 OR; (4) states, 1.43 OR; (5) age, 1.29 OR; and (6) a depression x facility interaction, 1.91 OR. PMID- 1890092 TI - The impact of curriculum-based suicide prevention programs for teenagers. AB - The impact of three school-based suicide prevention programs was assessed by comparing attitudes and knowledge of 758 9th and 10th graders with those of 680 control pupils, matched on age, ethnicity, and socioeconomic status at the school level, who did not receive the programs. Evaluations were conducted before exposure to the programs and again 1 month later. A large majority of students knew and subscribed to some of the more important program goals before exposure to the program. There was little evidence of program impact among the minority that did not. Most students were interested by the programs, and positive reactions were more common among female and minority students. PMID- 1890093 TI - A longitudinal study of suicidal ideation in young adolescents. AB - As part of a longitudinal study of depression and suicidal ideation in adolescents, a three-item suicide screen was administered to 1,073 students for 3 consecutive years starting at the beginning of the 7th or 8th grades. Each year over 70% of respondents reported no suicidal thoughts, and less than 5.5% attained high suicide ideation scores. Blacks and females had higher scores, respectively, than did whites and males. The individual students' suicide scores were less stable than the overall distributions with 1- and 2-year correlations reaching 0.35 and 0.28, respectively. Only one student received a high score all 3 years. The best predictors of a given year's suicide score was the previous years' depression scores. Gender, undesirable life events, family adaptability, and family cohesion were significant but less consistent predictors. PMID- 1890094 TI - Cognitive characteristics of adolescent suicide attempters. AB - The present study examined the relationship among psychiatric diagnosis, depression, attributional style, and hopelessness among 69 adolescent suicide attempters and 40 psychiatrically hospitalized adolescent controls. Contrary to predictions, the suicide attempters were more likely than the nonsuicidal group to attribute good events to global causes. No differences in attributional style were found across the depressed versus nondepressed subjects. However, there was a modest relationship between depression and attributional style. Results suggest that maladaptive cognitive characteristics are present in adolescent clinical samples but may be less specific to suicide attempters than is often suggested. PMID- 1890095 TI - Suicidal children grow up: demographic and clinical risk factors for adolescent suicide attempts. AB - This longitudinal study reports rates and demographic and clinical risk factors for adolescent suicide attempts during a 6- to 8-year follow-up period of an initial sample of 106 preadolescent and young adolescent psychiatric inpatients and 101 preadolescent and young adolescent nonpatients. Survival analysis was used to evaluate risk for a first suicide attempt in the follow-up period for 133 subjects who were interviewed. No deaths occurred. Suicidal inpatients, compared with nonpatients, had earlier first suicide attempts in the follow-up period. Adolescents who attempted suicide in the follow-up period were seven times more likely to have a mood disorder during the follow-up period than those who did not attempt suicide. Implications for clinical practice and research are discussed. PMID- 1890096 TI - Psychiatric diagnoses in minority female adolescent suicide attempters. AB - Psychiatric diagnoses were examined using the Schedule for Affective Disorders and Schizophrenia for School-Aged Children semistructured interview among three groups of minority adolescent females aged 12 to 17:61 suicide attempters, 31 psychiatrically disturbed nonattempters, and 23 nonattempting, nondisturbed girls. Major or minor depressive disorder was found in 42% of the suicide attempters; conduct disorder in 46%; multiple diagnoses in 38%, no diagnosis in 13%. These rates were very similar to those found in disturbed nonattempters. Only one symptom, suicidal ideation, distinguished attempters from disturbed nonattempters, while many symptoms distinguished these two groups from nondisturbed nonattempters. PMID- 1890097 TI - To whom do adolescents turn for help? Differences between disturbed and nondisturbed adolescents. AB - The focus of this investigation was to 1) identify those adolescents experiencing distress; 2) examine the formal and informal helping agents that adolescents seek out for help for emotional problems; and 3) describe adolescents' perceptions of the helpfulness of selected helping agents. Adolescents (N = 497) from three high schools in a large metropolitan area in the Midwest, representing a broad socioeconomic spectrum, were administered instruments related to self-image, delinquency, symptomatology, and help seeking. The prevalence rate of disturbance was 22.3%. Results show that disturbed adolescents sought help from alcohol/drug abuse centers, teenage drop-in centers, and mental health professionals more frequently than nondisturbed adolescents. In additional, both groups frequently sought help from parents and friends and perceived this help as beneficial. Implications of these findings for the development of adolescent mental health services are discussed. PMID- 1890098 TI - The role of somatic complaints in the diagnosis of depression in children and adolescents. AB - The question of whether somatic complaints are a significant feature of depression independent of anxiety was explored. Structured interview (Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children) and Child Behavior Checklist data from depressed and nondepressed psychiatric controls were analyzed to explore the interaction of somatic complaints, anxiety, and depression. Seventy percent of the children who met criteria for depression also had significant somatic complaints in contrast to 34% of the controls. Findings revealed that frequency of somatic complaints increased with severity of depression regardless of coexisting anxiety. PMID- 1890099 TI - The CES-D as a screen for depression and other psychiatric disorders in adolescents. AB - The performance of the Center for Epidemiologic Studies Depression Scale (CES-D) as a screen for depression was explored in a two-stage epidemiological study of adolescents. The study consisted of a CES-D screening stage completed by a school sample of 2,465 young adolescents and a structured psychiatric interview stage completed by 332 mother-adolescent pairs. Adolescents with interview validated depression had elevated screening scores (mean = 31.10, SD = 11.30) compared with individuals with no disorder (mean = 21.01, SD = 11.77). Using receiver operating characteristic curves, a cut point of 12 for males produced the best overall screening characteristics (sensitivity = 0.85, specificity = 0.49), while for females, a cut point of 22 was optimal (sensitivity = 0.83, specificity = 0.77). PMID- 1890100 TI - Interpersonal psychotherapy for adolescent depression: description of modification and preliminary application. AB - Interpersonal psychotherapy (IPT) is a brief treatment developed and tested specifically for depressed adults. This paper describes a modification for use with depressed adolescents (IPT-A) that will be tested in a controlled clinical trial. A description of IPT, its efficacy in adults, a rationale for developing IPT-A, and preliminary experience with depressed adolescents treated with IPT-A are presented. Data available on the treatment of depressed adolescents using drugs and/or psychotherapy is more than a decade behind that of adults. The specification and testing of psychotherapy will accelerate a rational, scientific basis for their treatment. PMID- 1890102 TI - The feasibility of conducting structured diagnostic interviews with preadolescents: a community field trial of the DISC. AB - A field trial of the Diagnostic Interview Schedule for Children, Version R, was conducted with a sample of 144 preadolescents identified from a 1986-1987 New Haven, Connecticut, cross-sectional children's mental health survey. This report examines procedural and methodological issues pertaining to the feasibility of completing structured diagnostic interviews with young children in the community. Four topics relating to community acceptance and potential response problems are addressed: 1) participation and completion rates; 2) quality of interview response; 3) parent and child reactions to the interview; and 4) evaluation of response bias. PMID- 1890103 TI - The utility of a DSM-III-R-based checklist in screening child psychiatric patients. AB - The Stony Brook Child Psychiatric Checklist, a parent completed rating instrument based on DSM-III-R, was used as part of a psychiatric inpatient admission evaluation. Data were collected on 63 5- to 13-year-old children. Checklist endorsements were compared with the same parent's responses to the Kiddie Schedule for Affective Disorders and Schizophrenia for School-aged Children Epidemiologic Version structured interview for the most frequently occurring disorders. Sensitivity scores ranged from 0.69 to 0.93. Results suggest the checklist can be useful in alerting the clinician to diagnostic areas warranting further pursuit. PMID- 1890101 TI - Child psychiatrists' views of DSM-III-R: a survey of usage and opinions. AB - The DSM-IV Child Psychiatry Work Group surveyed 460 child psychiatrists about their use of DSM-III-R and their reactions to specific proposed nosological revisions for DSM-IV. This paper presents the responses of the sample as a whole and of respondent subgroups with different theoretical, practice, and training characteristics. The survey indicates that DSM-III and DSM-III-R are widely used and generally accepted by child psychiatrists. Ninety-eight percent of respondents believe a criterion-based diagnostic system is useful, and 65% consider DSM-III-R to be an improvement over DSM-III. Depending on the diagnosis 47% to 66% of the respondents reported that they generally assess all applicable criteria and 28% to 49% often refer to the manual before assigning a diagnosis. A majority of respondents supported proposals for several new diagnostic subtypes. Ninety-three percent of respondents indicated that "adequacy of family support" was very valuable for treatment planning or estimating prognosis. Fifty-five percent of respondents admitted to diagnosing adjustment disorders in order to avoid the stigma associated with other disorders. Child psychiatrists who are psychodynamically oriented or practicing in an office-based setting or out of training for more than 10 years tend to use the DSM-III-R less rigorously. PMID- 1890104 TI - The use of a computer-assisted interview to administer the Child Behavior Checklist in a child psychiatry service. AB - This study describes the use of a computer-assisted interview to administer the Child Behavior Checklist to the parents of children referred to a child psychiatry service. The scores from the computer-assisted interview varied little from the scores obtained using the standard written checklist. Information collected by means of computer-assisted interviews with parents and children has the potential to facilitate the diagnostic assessment of individual children with emotional and behavioral problems, to provide a more comprehensive description of the work of child psychiatry services, and to encourage new clinical research by mental health professionals working in child psychiatry services. PMID- 1890105 TI - Commentary on unexplained death of children on Norpramin. PMID- 1890106 TI - Resolved: the pass rate for the child and adolescent psychiatry board examination should be higher than it is at present. PMID- 1890108 TI - Sexualized doll play. PMID- 1890107 TI - Forensic issues. PMID- 1890109 TI - European child psychiatry. PMID- 1890110 TI - Fluoxetine and suicidal ideation. PMID- 1890111 TI - Child psychopharmacology. PMID- 1890112 TI - Book review: the female fear. PMID- 1890114 TI - Bone allografts: the biological consequences of immunological events. PMID- 1890113 TI - IQ and reading progress. PMID- 1890115 TI - Observations on massive retrieved human allografts. AB - Radiographic and histological studies of sixteen massive retrieved human allografts were carried out after the allografts had been in situ for four to sixty-five months. The studies demonstrated that union between the allograft and the host took place slowly at cortical-cortical junctions by the formation of an external callus derived from the cortex of the host, and it took place more rapidly at cancellous-cancellous junctions by internal callus advancing from the host into the allograft. Internal repair took place very slowly, was confined to the superficial surface and the ends of the graft, and had involved only 20 per cent of the graft by five years. The deep unrepaired portions of the graft retained their architecture, and where bone cement had been used to fix a prosthetic stem or an intramedullary rod to the allograft, there was no evidence of resorption of bone or loosening of the device. Soft tissues of the host became attached to the graft by deposition of a thin seam of new bone on the surface of the graft. A previous fracture of two grafts had healed before the time of retrieval. Analysis of the articular cartilage revealed no evidence that any chondrocytes had survived, even when the graft had been cryoprotected before it was preserved by freezing. The necrotic cartilage functioned well for as long as five years, and as it degenerated, it was covered by a pannus of fibrovascular reparative tissue. Two allografts that had been removed because of rejection were surrounded by an envelope of chronic inflammatory tissue that prevented union, adherence of soft tissue, and internal repair. Internal repair was more advanced about sites of fracture and adjacent to recurrent tumors than in other portions of the graft. These findings suggest that large frozen allografts in humans are osteoconductive rather than osteoinductive. PMID- 1890116 TI - The fate of cancellous and cortical bone after transplantation of fresh and frozen tissue-antigen-matched and mismatched osteochondral allografts in dogs. AB - After implantation, a massive osteochondral allograft cannot be completely protected from the stresses that are produced by weight-bearing, and it is susceptible to collapse during incorporation, revascularization, and substitution. How these processes are affected by disparities between the tissue antigens of the host and the graft remain unclear. To clarify the role of histocompatibility antigen-matching in the incorporation of cancellous and cortical bone, we orthotopically implanted both fresh and cryopreserved dog leukocyte-antigen-matched and mismatched proximal osteochondral radial allografts in beagles. Four groups of beagle dogs were used; they received (1) a dog leukocyte-antigen-mismatched frozen allograft, (2) a dog leukocyte-antigen mismatched fresh allograft, (3) a dog leukocyte-antigen-matched fresh allograft, or (4) a dog leukocyte-antigen-matched frozen allograft. In twelve dogs, a sham operation was done in the contralateral limb (the first living donor had a sham operation), and in the remaining ten dogs, the proximal part of the contralateral radius was removed and then replaced as an autogenous (control) graft. The animals were given fluorochromes periodically, and they were killed eleven months after the operation. The osseous portion of the grafts was evaluated radiographically, biomechanically, and histomorphometrically. No dog had grossly obvious clinical abnormalities, all host-graft interfaces healed, and no joints dislocated. Radiographic examination of the allografts frequently showed deformation of the radial head and variable peripheral resorption. No significant difference in the modulus of elasticity at the host-graft interface was found among the groups. The repair process of the cortical bone was similar for all grafted segments. New periosteal and endosteal bone formed, and the cortical bone became porotic as vessels penetrated it. The uptake of fluorochrome was the most active in the autogenous grafts and the least active in the fresh antigen mismatched grafts. The volume of cancellous bone was significantly greater and the trabeculae were thicker in all allografts compared with the bones on which a sham operation had been done and compared with the autogenous grafts. The volume of intertrabecular fibrous connective tissue was directly proportional to the immunogenicity of the allografts, and the percentage of the surface on which bone was forming tended to be inversely proportional to the immunogenicity of the allografts. The grafts were revascularized by the ingrowth of vessels into the intertrabecular spaces; necrotic trabeculae were not penetrated by vessels. This pattern was particularly pronounced in the antigen-mismatched grafts, regardless of whether they were fresh or frozen.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1890117 TI - Unwashed filtered shed blood collected after knee and hip arthroplasties. A source of autologous red blood cells. AB - We evaluated the results of twelve hematological and plasma protein determinations in 450 to 500-milliliter volumes of shed blood that had been collected with or without acid-citrate-dextrose anticoagulant (National Institutes of Health Formula A) from knees and hips during the first twelve hours after arthroplasty. We also evaluated the effects on the recipients when the blood was used for reinfusion. The findings in the units that had been obtained in less than four hours, in between four and six hours, and in more than six hours after the arthroplasty were similar whether or not the acid-citrate dextrose anticoagulant had been used. The mean values for the collected units were: in the blood, a concentration of hemoglobin of 115 grams per liter, a hematocrit of 0.34, a white blood-cell count of 4.8 x 10(9) per liter, and a red blood-cell count of 3.7 x 10(12) per liter, and, in the plasma, a level of hemoglobin of 160 grams per liter, a level of fibrinogen of less than 0.2 gram per liter, a level of factor-V clotting protein of less than 10 per cent of normal, a level of factor-VIII clotting protein that was 45 per cent of normal, a level of antithrombin III that was 45 per cent of normal, a level of plasminogen that was 55 per cent of normal, a level of protein C that was 100 per cent of normal, and a level of fibrin-degradation products of 1000 micrograms per milliliter of plasma. The clinical response of the patient was assessed after the reinfusion of a total of 205 units of unwashed shed blood into 153 patients. In addition, in 126 of the 153 patients, hematological and plasma-protein measurements were analyzed before the autotransfusion and one and twenty-four hours afterward. Each of these patients had received one to four units of shed blood that had been filtered but not washed. Only two (2 per cent) of the ninety nine patients who received shed blood that had been collected six hours or less after the operation had a febrile reaction, whereas twelve (22 per cent) of the fifty-four patients who received blood that had been collected six to twelve hours after the operation had such a reaction.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1890118 TI - Results of spinal arthrodesis with pedicle screw-plate fixation. AB - Sixty-one patients were followed for an average of thirty months (range, twenty four to thirty-five months) after arthrodesis of the lumbar or lumbosacral spine with pedicle screw-plate fixation for painful degenerative arthritis, spondylolisthesis, or pseudarthrosis. The patients rated the clinical result according to an analog scale. Most patients reported a marked decrease in pain and an increase in function, and two-thirds were able to work full time. The result of the operation was regarded as a clinical failure if the patient considered it so, if an additional operation had been done, or if the functional and pain scores were not good (that is, if the patient was not able to work full time and the rating for pain was more than 5 of 10 points). Seventeen (28 per cent) of the patients were considered to have a clinical failure, with the lowest rate (20 per cent) for patients who had painful degenerative arthritis and the highest rate (47 per cent) for patients who had had a pseudarthrosis before the operation. The rate of fusion was 90 per cent in patients who had painful degenerative disease, 93 per cent in patients who had spondylolisthesis, and 65 per cent in patients who had had a pseudarthrosis preoperatively. PMID- 1890120 TI - A new device for the fixation of unstable pertrochanteric fractures of the hip. AB - A new type of fixation device for the treatment of pertrochanteric fractures of the hip is described. The device has an axial-compression screw to allow compression along an axis parallel to the femoral shaft. As the fracture settles postoperatively, dynamic axial compression continues. This axial-compression device was used in twenty-five patients who had an unstable intertrochanteric or proximal subtrochanteric fracture of the proximal part of the femur. The average extent of axial impaction or settling was five millimeters (standard deviation, 1.3 millimeters) at the most recent follow-up examination, and the relationship between the femoral head and shaft was altered less than with the use of a conventional compression screw-plate device. A larger proportion of the patients who had the new device were able to walk fifteen meters (fifty feet) independently by the time of discharge from the hospital, even though they left the hospital earlier. No technical failures were seen in the patients who were treated with the axial-compression screw device. We believe that the axial compression screw-plate device is appropriate for the treatment of unstable pertrochanteric fractures of the hip. PMID- 1890119 TI - Long-term roentgenographic and functional changes in patients who were treated with wide fenestration for central lumbar stenosis. AB - Thirty-four patients who had central stenosis of the lumbar spine were treated with wide fenestration, a procedure in which only the medial parts of the inferior facets and the adjoining ligamentum flavum were removed. The patients were followed for an average of five and one-half years (range, four and one-half years to seven years and ten months). Wide fenestration successfully relieved the symptoms. The new bone that was laid down in the operatively treated segments did not reproduce the symptoms of spinal stenosis; instead, it appeared to stabilize those segments. PMID- 1890121 TI - The importance of positive bacterial cultures of specimens obtained during clean orthopaedic operations. AB - Microbiological cultures of specimens of tissue and of fluids from the wound in forty patients who had had consecutive clean, elective orthopaedic operations (excluding total joint replacements) and had not received antibiotics preoperatively were analyzed. Of the forty patients, twenty-three (58 per cent) had a positive culture on at least one of the media that were used and seventeen (43 per cent) had negative cultures. Of the forty specimens that were obtained from swabbing of the wound, eight (20 per cent) were positive on culture, compared with twenty (50 per cent) that were obtained from biopsy of tissue. Of these twenty-eight positive cultures, thirteen (46 per cent) were on routine blood-agar plates and fifteen (54 per cent), in broth only. Of the thirty-three bacterial organisms that were identified in the twenty-eight positive cultures of the wound, nineteen (58 per cent) were coagulase-negative Staphylococcus; eight (24 per cent), Propionibacterium acnes; two (6 per cent), Peptostreptococcus; and four (12 per cent), miscellaneous organisms. In all of the positive cultures on the blood-agar plates, except in those showing Propionibacterium acnes, there were five colonies or fewer. One patient had a clinical infection with Staphylococcus aureus that developed later, but the initial cultures of the wound had been positive for Staphylococcus epidermidis only. None of the bacteria that grew on culture were Staphylococcus aureus or the less common pathogenic gram negative bacteria, such as Escherichia coli, Pseudomonas, or Klebsiella.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1890122 TI - Vibratory response in adolescents who have idiopathic scoliosis. AB - The PVD Bio-Thesiometer was tested as a tool for measuring vibratory thresholds and for detecting possible differences in these thresholds between adolescents who have idiopathic scoliosis and those who do not. It was found to be limited by low reliability and large errors in measurement, with the metatarsophalangeal joint being the only reliable site for measurement. The vibratory thresholds at this site were significantly higher in the fourteen subjects who had scoliosis than in the twenty-two control subjects. No significant asymmetry in vibratory thresholds was found between the concave and convex or the right and left sides in either the scoliotic or the control group. Because there was no significant difference between the readings from the concave and convex sides, it is unlikely that a lesion of the posterior column is responsible for idiopathic scoliosis. If there is a difference, then the PVD Bio-Thesiometer is not sufficiently reliable to detect it. PMID- 1890123 TI - Open reduction and internal fixation of two-part displaced fractures of the greater tuberosity of the proximal part of the humerus. AB - Twelve patients, ranging in age from thirty-four to seventy-two years (average, fifty-three years), were evaluated an average of five years (range, two to eight years) after open reduction and internal fixation of a two-part displaced fracture of the greater tuberosity of the proximal part of the humerus. The indication for operative reduction was one centimeter or more of displacement of the fracture as seen on the diagnostic radiographs. The anterosuperior deltoid splitting approach, combined with rotation of the humerus, allowed adequate exposure of the retracted tuberosity. Internal fixation of the greater tuberosity with heavy, non-absorbable sutures and careful repair of the rotator cuff permitted early passive motion. All fractures healed without postoperative displacement. Six patients had an excellent result and six had a good result; active elevation averaged 170 degrees. There was one partial, transient palsy of the axillary nerve. PMID- 1890124 TI - Non-union of fractures of the mid-shaft of the clavicle. Treatment with a modified Hagie intramedullary pin and autogenous bone-grafting. AB - We reviewed a series of fifty patients who had a non-union of a fracture of the clavicle. Twenty-one patients (42 per cent) who had a symptomatic non-union of the middle of the shaft of the clavicle were treated with open reduction, internal fixation with a modified Hagie intramedullary pin, and autogenous bone grafting, and those patients form the basis for the report. The average duration of follow-up was thirty-five months (range, five months to eleven years). Healing occurred in twenty (95 per cent) of the twenty-one patients. Intramedullary fixation has several advantages compared with other treatments, such as fixation with a plate and screws. It can be performed through a cosmetically acceptable incision in the Langer line; less dissection of the soft tissues is needed; and, after healing, the pin can be removed through a small incision under local anesthesia. PMID- 1890125 TI - Use of the Souter-Strathclyde total elbow prosthesis in patients who have rheumatoid arthritis. AB - Thirty-three patients had thirty-four consecutive primary arthroplasties, with use of the Souter-Strathclyde cemented unconstrained prosthesis, for severe rheumatoid arthritis of the elbow. The minimum duration of follow-up for inclusion in the study was two years. Three patients died. Four arthroplasties were revised: three, because of irreducible dislocation immediately after the operation and one, because of loosening without infection. One prosthesis was removed because of a late deep infection. In most of the remaining twenty-five patients (twenty-six arthroplasties), who had an average duration of follow-up of four years (range, two to eight years), pain was markedly less or had resolved completely, and the function of the elbow was greatly improved. PMID- 1890126 TI - Magnetic resonance imaging in the evaluation of partial growth arrest after physeal injuries in children. AB - The precise delineation of the size, shape, and location of an osseous bridge is a critical step in the management of children who have a partial growth arrest of the epiphyseal plate. Five children between the ages of ten and fourteen years were diagnosed, with the aid of conventional roentgenograms, as having a partial growth arrest. Magnetic resonance-imaging studies were carried out to determine the exact size, shape, and location of the osseous bridge. The information derived from the imaging studies was essential for the determination of the appropriate treatment and for the planning and undertaking of any operative intervention. PMID- 1890127 TI - Intra-articular fractures of the distal part of the radius treated with the small AO external fixator. AB - Thirty adults who had a severely comminuted intra-articular closed fracture of the distal part of the radius were treated by closed reduction and AO external fixation consisting of a converging-pin configuration with a double row of connecting bars. The patients were followed for an average of 2.6 years (range, two to four years). Twenty-seven patients had an excellent result; two, a good result; and one, a poor result, on the basis of pain, motion, strength, and radiographic appearance. Complications were rare, and there was no loss of fixation of the pins. The average grip strength was 92 per cent of normal. Motion of the wrist and rotation of the forearm averaged more than 90 per cent of that of the normal side. Carpal height was used as an indicator of distraction force produced by the fixator. There was an average increase in carpal height of four millimeters initially and 3.7 millimeters immediately before removal of the fixator, indicating near-constant distraction throughout the treatment. Radial length was well maintained, with shortening averaging less than one millimeter. The converging pins of the AO fixator prevent loosening, thereby diminishing the risks of infection, loss of reduction of the fracture, and breakage of the pins. This geometry of the pins allows the use of smaller-diameter (2.5-millimeter) pins and provides rigid fixation, even in osteoporotic bone. PMID- 1890128 TI - The symptomatic os subfibulare. Avulsion fracture of the fibula associated with recurrent instability of the ankle. AB - Four adults who had symptomatic instability of the ankle had an associated os subfibulare. Operative exploration revealed the ossicle to represent a non-union of an avulsion fracture of the anterior talofibular ligament. These findings suggest that an os subfibulare represents an avulsion fracture that may or may not be associated with laxity of the anterior talofibular ligament, rather than being a normal variant. PMID- 1890129 TI - Bilateral deficiency of ossification of the lunate bone. A case report. PMID- 1890130 TI - Therapeutic embolization of false aneurysms of the superior medial genicular artery after operations on the knee. A report of two cases. PMID- 1890131 TI - Magnetic resonance imaging of a rupture of the medial head of the gastrocnemius muscle. A case report. PMID- 1890132 TI - Chemotherapy for bone and soft-tissue sarcomas of the extremities. PMID- 1890134 TI - Amputation or limb-lengthening for partial or total absence of the fibula. PMID- 1890133 TI - Acetabular anatomy and the transacetabular fixation of screws in total hip arthroplasty. PMID- 1890135 TI - Results of treatment of displaced patellar fractures by partial patellectomy. PMID- 1890136 TI - Carcinogen-induced liver tumours of Wistar rats: absence of activated ras genes and of N-rasC. AB - We examined mutational activation of ras genes in rat liver preneoplasias and tumours induced by diethylnitrosamine and N-methyl-N-nitrosourea (NMU). In accordance with previous reports on H- and K-ras genes, no mutations were detected in the investigated hepatic tumours and prestages suggesting that neither mutations at codons 12, 13 and 61 of H- and N-ras nor a mutation in the last intron of the H-ras gene are involved in initiation and progression of rat hepatocellular carcinomas. In the course of this investigation we found two N-ras genes (N-rasA, N-rasB). Surprisingly N-rasC, which is present in the germ line of Fischer rats, is missing in Wistar rats. This suggests different numbers of germline N-ras genes in members of one species. Two out of eight NMU-induced liver tumours exhibited additional N-ras-related sequences of unknown origin. PMID- 1890137 TI - Investigation into the immunological effects of miltefosine, a new anticancer agent under development. AB - Miltefosine is the prototype of alkylphosphocholines, a new class of anticancer agents related to alkyl-lysophospholipids. These agents were considered to possess potent immunomodulatory properties. Miltefosine was highly active against the human KB tumour xenograft in nude mice, leading to growth inhibition as well as regression of large established tumours, which suggested that its mode of action was not mediated by the T cell system. In vivo natural killer cell activity was measured by chromium release of YAC-1 cells using spleen cells from treated animals as effector cells. Miltefosine had no significant effect on YAC-1 cytolysis. Similarly, the compound did not induce cytotoxic spleen cells against KB target cells. The results were identical when spleen cells from tumour-bearing animals were used. Humoral antibody production in rats following sheep red blood cell immunization was not changed by miltefosine pretreatment. Finally, the in vitro phagocytic activity of mouse bone marrow macrophages was not stimulated but rather inhibited in a dose-dependent manner. In conclusion, there is no experimental evidence that the miltefosine action is mediated by the host immune system and no major immunotoxicity was observed. PMID- 1890138 TI - The morphology, deformability and microvascular arrest of rat fibrosarcoma and adenocarcinoma cells. AB - The deformation and flow properties of tumour cells may play a role in their arrest in the microvasculature of different organs. In the present investigation the morphology, deformability and microvascular arrest in the liver of rat fibrosarcoma cells (FSCs) and adenocarcinoma cells (ACCs) were compared using electron microscopy, deformability measurements in narrow glass pipettes and isotope-labelling techniques. The ACCs had a larger mean diameter (13.9 microns) than the FSCs (10.9 microns) and showed a slower rate of deformation into 6.5 microns glass pipettes. A significantly larger percentage of ACCSs (52.4%) than of FSCs (19.9%) remained in the livers 5 min after intraportal injection. The results indicate that for the particular tumour cells studied here, there exists a relationship between cell deformability and the tendency for microvascular trapping in the liver, i.e. less deformable cells have a greater tendency for retention in the liver. PMID- 1890139 TI - Different response of murine and human mammary tumour models to a series of diastereoisomeric [1,2-bis(difluorophenyl) ethylenediamine]dichloroplatinum(II) complexes. AB - A series of isomeric [1,2-bis(difluorophenyl) ethylenediamine]dichloroplatinum(II) complexes and cisplatin were tested on the P388 leukemia and on the murine hormone-independent MXT (M3.2) OVEX and the ovarian-hormone-dependent MXT (M3.2) mammary carcinoma for evaluating antineoplastic activity against breast cancer in vivo. Although these results were heterogeneous, a trend to the 2,6-difluorosubstituted compound as the most active platinum complex was observed. For the development of a large-scale in vitro screening method on human breast cancer cell lines, cell number, [3H]thymidine incorporation, and crystal violet staining were evaluated as parameters for end-point determination. Chemosensitivity testing on the human breast cancer cell lines MDA-MB-231 and MCF-7 unambiguously identified [1,2 bis(2,4-difluorophenyl)ethylenediamine]dichloroplatinum(II) as the complex with the highest activity in the crystal violet micro-assay. In equimolar concentration this compound was superior to cisplatin on both cell lines. The analysis of the conflicting results of this study indicates that murine mammary carcinomas are most probably unrealistic and inappropriate models for the screening of cytotoxic platinum complexes with potential activity on human breast cancer. PMID- 1890140 TI - Growth, ribonucleotide reductase and metals in murine leukemic lymphocytes. AB - Trace metals are essential for the growth and several other properties of human lymphocytes. We studied the effects of media with variable concentrations of three metals (Fe2+, Cu2+, Zn2+), a metal chelator (deferoxamine, DFX) and a cell growth inhibitor (hydroxyurea) on the growth, intracellular metal concentration and activity of the enzyme ribonucleotide reductase in murine leukemic lymphocytes (L1210). Intracellular concentrations of Fe and Cu fluctuated within narrow limits in normal media, but decreased to very low concentrations in metal poor media. The intracellular Zn concentration did not vary appreciably. Growth in intact cells decreased by 50%-70% when normal media were replaced by metal poor media, but returned to control values when media were supplemented with gradually increasing concentrations of Fe and Cu. Fe and Cu had synergistic effects, while Zn had no stimulatory action. Hydroxyurea and DFX both inhibited cell growth, but only DFX inhibition was reversed by addition of metals. The addition of the above metals and inhibitors to the cell extracts produced effects on ribonucleotide reductase activity similar to those observed on the growth of whole cell preparations (stimulation by Fe and Cu, inhibition by Zn, DFX and hydroxyurea). These findings show that (a) the intracellular metal concentration is maintained in a narrow range during cell growth; (b) ribonucleotide reductase activity varies with cell growth; (c) ribonucleotide reductase activity and cell growth increase with Fe and Cu and decrease with Zn and DFX. Our data suggest that (a) Fe, Cu and Zn may have some effect on the growth and ribonucleotide reductase activity of L1210 cells, that (b) Fe, Cu and Zn may operate in a related and interdependent way and that (c) DFX inhibits cell growth probably through inhibition of the reductase activity and chelation of the Fe of its Fe containing subunit. We conclude that any study on one of these metals should always include the other two and that manipulation of intracellular metals should be investigated as a potential therapeutic modulator of growth in leukemic lymphocytes. PMID- 1890141 TI - Y/6 chromosome translocation in a male with triple primary cancers involving the breast. AB - Cytogenic studies were performed in a 72-year-old male patient with triple primary cancers including breast, skin and lung. Left breast cancer was diagnosed at the age of 46 and he received mastectomy and thoracic irradiation. Squamous cell carcinoma and Bowen's disease were diagnosed from two separated parts of a skin lesion at the age of 70. Small-cell lung cancer was diagnosed 1 year later, and he received chemotherapy and radiotherapy. Chromosome analysis was carried out on both peripheral lymphocyte and skin fibroblast cultures at the age of 72. Out of 30 fibroblast cells karyotyped at the second passage, 7 cells (23%) consistently showed a reciprocal translocation t(Y;6)(q12;p21). The same translocation was found in one of 200 cells from lymphocyte cultures. The findings suggest that the translocation t(Y;6) might be inherent in nature, and that the patient was a mosaic of 46,XY/46,X,t(Y;6)(q12;p21). These results highlight the constitutional chromosomal abnormality as one of the possible high risk factors for multiple primary cancers. PMID- 1890143 TI - Comparative analysis of cancer-associated antigen CA-195, CA 19-9 and carcinoembryonic antigen in diagnosis, follow-up and monitoring of response to chemotherapy in patients with gastrointestinal cancer. AB - To establish further the clinical significance of the CA-195 tandem immunoradiometric assay in gastro-intestinal malignancies, the sera of a total of 222 subjects have been analysed and compared with assays of the "classical gastrointestinal tumour markers", CA19-9 and carcinoembryonic antigen (CEA). CA 195 elevations above normal (greater than 10 U/ml) were noted in 51/72 (70.8%) colorectal, 15/15 (100%) pancreatic, and in 6/12 (50%) gastric cancer patients. Whereas CA19-9 was increased (greater than 37 U/ml) in 65%, 93%, and 42% of cases, only 54% colorectal, 45% pancreatic, and 42% gastric cancer patients had pathologically elevated serum CEA levels (greater than 5 ng/ml). No abnormal increase of both CA-195 and CA19-9 was found in healthy volunteers, whereas 3/20 (smoking) individuals had CEA levels slightly above normal. With a 29% false positive rate noted among 103 patients with benign gastrointestinal disorders, the specificity of CA-195 was superior to that of CA19-9 (58%) and comparable with that of CEA (31%). A significant correlation between CA-195 levels and the clinical/pathological stage of disease was noted in colorectal (P less than 0.01) and pancreatic cancer patients (P less than 0.007). Preliminary results of serial measurements of CA-195 in colorectal cancer suggest that this new marker protein, which has no cross-reactivity with CEA, may be useful as a non-invasive test for postoperative surveillance of patients to detect disease recurrence, and serve to complement (though certainly not replace) standard clinical measurements of response to chemotherapy. PMID- 1890142 TI - Five-day 4'-(9-acridinylamino)methanesulphon-m-anisidide and intermediate-dose cytosine arabinoside in high-risk relapsing or refractory acute myeloid leukemia. AB - Twenty-two patients with acute myeloid leukemia (AML), having a median age of 48.3 years (range 26-70; 10 male, 12 female), were treated with 4'-(9 acridinylamino) methanesulphon-m-anisidide (m-AMSA) 100 mg/m2 and cytosine arabinoside (AraC) 2 x 1000 mg/m2i.v. on days 1-5. There were 2M1,8 M2, 9 M4, 2M4 Eo, and 1 M5a. Of these, 12 achieved a complete remission, 3 a partial remission and 6 did not respond. The median remission duration was 9.0 months and the median overall survival 8.1 months. Side-effects of induction consisted mainly of haematological toxicity and infections with a median duration of WHO-grade-4 granulopenia and thrombopenia of 20 and 28 days respectively. Organ toxicity was mild with mucositis and cutaneous and liver toxicity being experienced by only a few patients. There was one treatment-related death. Five-day m-AMSA and intermediate-dose AraC is an easy-to-handle condensed treatment schedule with tolerable toxicity. Its effectiveness in relapsed and refractory AML is comparable to combinations of high-dose AraC with m-AMSA, anthracyclines or etoposide. PMID- 1890145 TI - Case of a 2-year-old boy with a unilateral retinoblastoma followed by a second neoplasm resembling neuroblastoma. PMID- 1890144 TI - Cancer mortality in young adults in Switzerland, 1951-1989. AB - Trends in mortality from all neoplasms and major cancer sites in Switzerland among populations aged between 20 and 44 years are presented. In men total cancer mortality was approximately constant around 270/10(6) between 1951 and 1965, but declined appreciably thereafter to 217 per million in 1980-1989. The overall fall was 20%. The pattern of trends was similar for women, although a modest decline was already apparent in the earlier calendar period, and the overall fall was 29% (from 303 to 215/10(6)). These favourable trends reflect therapeutic advancements for Hodgkin's disease, leukaemias, testis and (chiefly non-epithelial) ovarian cancer, better control of cervical cancer, the long-term decline in gastric cancer, but also the downward trends in cancer of the intestines and a few less common sites, such as gallbladder and thyroid neoplasms for reasons that are not yet clear. Appreciable rises were observed for lung and other tobacco-related sites in women, for the oral cavity in men and (in earlier calendar periods) cutaneous melanoma in both sexes. Although restricted to a selected number of sites, these rises are discouraging, since the causes of these neoplasms have long been recognized. Somewhat discouraging also is the absence of decline in male lung cancer. These problems notwithstanding, the overall pattern of trends in cancer mortality in young Swiss adults over the last few decades is still reassuring, particularly in comparison with those observed in other European countries, and in the more general framework of the debate on the perspectives of progress in cancer control. Although restricted to a small proportion of all cancer deaths, in fact, trends in young adults offer useful indications on the likely future trends in the same generations in the near future, since they reflect more recent changes in the pattern of exposure. The size of the changes, however, will probably differ, since the prevalent cancers in middle age are different from those in the young. PMID- 1890146 TI - Clinical review 26: Insulin resistance in obese and nonobese man. PMID- 1890147 TI - Characteristics of 3,5,3'-triiodothyronine sulfate metabolism in euthyroid man. AB - The sulfated conjugate of T3 (T3S) has long been recognized as a normal product of peripheral thyroid hormone metabolism. In order to better understand the role that T3S may play in this process, the metabolic handling of T3S was studied in euthyroid man. After the iv administration of [125I]T3S in man, T3S was found to be rapidly metabolized with estimated mean MCR of 135 +/- 15 liters/day (L/D) after a bolus injection and 127 +/- 8 L/D employing a constant infusion. The primary route of T3S disposal was by deiodination with an efficiency of 92%. The administration of propylthiouracil (PTU, 300 mg every 6 h x 5 days) and iopanoic acid (IA, 500 mg every day x 5 days), both inhibitors of deiodination, decreased clearance compared to control (87 +/- 9 L/D, P less than 0.01 and 46 +/- 10 L/D, P less than 0.002, respectively). A 3-day fast also reduced the clearance of T3S (56 +/- 10 L/D, P less than 0.002). All three maneuvers decreased the total urinary deiodination fraction of tracer T3S (control 91 +/- 2%, PTU 70 +/- 9%, P less than 0.04, IA 26 +/- 3%, P less than 0.0001, and fasting 58 +/- 6%, P less than 0.01). A strong correlation between T3S clearance and deiodination was noted for fasting and IA only (r = 0.78, P less than 0.003). However, no relationship between clearance and deiodination was noted with PTU administration presumably as a result of a compensatory increase in biliary losses of T3S. The urinary thyronine excretion pattern demonstrated the presence of small amounts of labeled T3,3,3'-T2, and 3,3'-T2S with the major metabolite being T3S itself. TSH levels were not influenced by the infusion of stable T3S designed to achieve a serum value greater than 50 ng/dL. No absorption of intact T3S was detected after its oral ingestion. In conclusion, T3S is rapidly cleared from the serum, primarily by deiodination, may undergo nondeiodinative disposal when hepatic deiodination is inhibited by PTU but not with IA or fasting, and has no intrinsic biological activity. Thus, T3S may serve as a metabolite of T3 for its rapid deiodinative disposal. Although the precise role T3S plays in human thyroid hormone metabolism has not been defined, the metabolic characteristics of T3S appear similar to that of an unidentified alternate T4 metabolite formed in low T3 states of fasting and nonthyroidal illness. PMID- 1890148 TI - Expression of aromatase cytochrome P-450 in premenopausal and postmenopausal human ovaries: an immunocytochemical study. AB - The cellular distribution of the aromatase cytochrome P-450 enzyme in human ovaries has been investigated immunocytochemically, using an aromatase-specific monoclonal antibody. Ovaries of females ranging in age from prepubertal infant girl through to postmenopausal adulthood were obtained from immediate autopsy or after surgery. The results have revealed temporal and spatial changes in expression of aromatase at different stages of development. No immunoreactive aromatase was detected in the ovary of the 2.5 month infant. In premenopausal ovaries, aromatase was absent from the stromal compartment, but in follicles, a consistent pattern in expression of aromatase was observed, related to their size and developmental stage. Aromatase was not expressed in primordial, primary, or small secondary follicles less than 250 microns diameter. In slightly larger follicles (250-700 microns diameter) aromatase was first detected in a few thecal cells (TC). In more developed secondary through to large preovulatory follicles (greater than 1 cm) TC aromatase immunostain increased in intensity and number of positive cells, and the reaction was localized to a band of theca interna (TI) cells at the TI/theca externa interface. In granulosa cells (GC), aromatase was first detected in follicles in the initial stages of antrum formation (greater than 700 microns), and staining intensified as follicle diameter and antral cavity increased, being maximal in preovulatory follicles. GC aromatase was always found in the presence of TI immunostain. These two cell populations were separated by an unstained layer of TI cells giving the follicle walls a banded appearance. Immunostain was most intense in mural GC, was weaker in antral GC cells and was absent from the cumulus GC. Immunoreactive aromatase was also detected in functional corpora lutea (CL) but was absent from involuting CL's and corpora albicans. Our findings indicate that the immunostained cells of the CL are comprised of the former GC and possibly a subpopulation of former TI cells. In perimenopausal ovaries there was no evidence of any follicular or stromal aromatase immunostain. In postmenopausal ovaries no follicles were observed, but individual cells and clusters of cells in the stromal compartment of 3/7 specimens were found to have an aromatase immunostain reaction. In all cases, the aromatase immunostain reaction was cytoplasmic. The results provide the first direct evidence of the existence of TC aromatase, and of stromal cell aromatase in postmenopausal women. PMID- 1890149 TI - Detection, cellular localization, and modulation of heat shock proteins in cultured fibroblasts from patients with extrathyroidal manifestations of Graves' disease. AB - We hypothesize that fibroblasts obtained from the retroocular space and the pretibial skin, sites affected by the peripheral manifestations of Graves' disease, share unique characteristics that may in part explain the site specificity of Graves' ophthalmopathy (GO) and pretibial myxedema (PTM). Heat shock proteins (HSPs), synthesized by cells undergoing stress, function to maintain cellular homeostasis and are probably involved in the intracellular processing and cell surface presentation of antigens. We investigated possible differences in the expression of 70-kDa HSPs between cultured fibroblasts obtained from patients with severe GO and normal individuals. In addition, we compared HSP expression in fibroblasts derived from tissues involved in the extrathyroidal manifestation of Graves' disease (GO and PTM) with that in fibroblasts from uninvolved tissues. HSPs were detected by both immunoblotting and indirect immunofluorescence, using monoclonal antibodies that are directed against HSP72, HSP72/73 (termed HSP70), and HSP90. HSP expression at baseline and after treatment with various cytokines and heat stress was examined. At baseline, HSP72 reactivity was exclusively detected in retroocular and pretibial fibroblasts from patients with severe GO and PTM, but was not observed in abdominal fibroblasts from these patients and was not detectable in fibroblasts from any anatomical site of normal individuals. The abundance of HSP70 expression at baseline and after treatment with certain cytokines was significantly greater in retroocular and pretibial fibroblasts from patients with GO than in normal individuals. In addition, characteristic changes in the cellular localization of HSPs before and after exposure to heat stress and cytokines were observed; cell surface expression of HSP70 was detected at baseline in fibroblasts from patients, but not in normal fibroblasts. These data provide the first evidence that HSPs are differentially expressed by fibroblasts derived from tissues affected by the extrathyroidal manifestations of GD. These proteins may have a role in localized immune processes, leading to the development of GO and PTM. PMID- 1890150 TI - Contribution of postprandial insulin and glucose to glucose disposal in normal and insulin-resistant obese subjects. AB - We recently found that postprandial hyperinsulinemia does not compensate for the insulin resistance of obese subjects and proposed that postprandial hyperglycemia might be more important in promoting glucose disposal via the mass action effect of glucose. To test this idea we perform oral glucose tolerance tests (OGTT) in six lean and eight obese subjects, measuring glucose and insulin levels. Afterward two insulin infusion studies were performed. During infusion study I, insulin was infused in a dynamic square wave fashion to mimic the individual post OGTT insulin levels at content euglycemic glucose levels. During study II, glucose and insulin infusions were varied to mimic post-OGTT levels in each subject. Overall glucose turnover was measured isotopically by infusion of [3-3H] glucose. During the OGTT the obese subjects exhibited significantly higher insulin (P less than 0.005) and glucose levels (P less than 0.002). Insulin stimulated glucose disposal rates and total incremental glucose disposal (IGD) over 4 h during study I at euglycemia were significantly lower in obese compared to lean subjects (area under the curve, 824 +/- 166 vs. 1222 +/- 161 mmol/L.m2; P less than 0.01) despite higher post-OGTT insulin levels in obese subjects. When insulin plus glucose levels were matched to the individual OGTT levels, IGD was not significantly different between obese and control subjects (1712 +/- 253 vs. 1617 +/- 444 mmol/L.m2; P = NS). A significant inverse correlation (r = -0.73; P less than 0.05) existed between the degree of glucose intolerance (OGTT) and the decrease in IGD during the phasic hyperinsulinemic euglycemic study (infusion study I). These data suggest that with increasing insulin resistance, hyperinsulinemia is less effective in compensating for this decrease in insulin action, and hyperglycemia becomes more important in augmenting overall glucose disposal values. PMID- 1890151 TI - Hypothalamic modulation of growth hormone secretion in the rhesus monkey: evidence from intracerebroventricular infusions of glucose, free fatty acid, and ketone bodies. AB - To evaluate the hypothalamus as a possible site of metabolic modulation of GH secretion, we studied the GH response to insulin hypoglycemia (IHG) and nicotinic acid (NA)-induced FFA depression in the absence and presence of third ventricular (ivt) infusions of glucose, oleic acid (Ol-Ac), or beta-hydroxybutyrate (beta OHB). Four rhesus monkeys had been prepared for chronic remote iv and ivt infusions as well as blood sampling from the adjacent room. Statistical evaluation used a two-way analysis of variance and individual comparisons with Tukey's Studentized range test. The GH response (area under the curve +/- SE) to IHG was significantly reduced by a concomitant ivt glucose infusion (control, 1.0 +/- 0.1; IHG, 12.1 +/- 3.3; IHG plus ivt glucose, 7.0 +/- 1.2 microgram/L.120 min). The GH response to FFA depression was significantly reduced by ivt Ol-Ac or beta OHB infusion (control, 6.0 +/- 1.0; NA, 51.5 +/- 4.1; Na plus Ol-Ac, 81.2 +/ 1.3; NA plus beta OHB, 38.6 +/- 3.5 microgram/L.300 min). Introcerebroventricular infusions of glucose, Ol-Ac, or beta OHB alone had no effect on plasma GH, glucose, FFA, or beta OHB concentrations. These results provide evidence for a hypothalamic site of metabolic modulation of GH secretion in the rhesus monkey. This does not exclude an additional effect directly at the pituitary gland. PMID- 1890152 TI - Decreased serum growth hormone-binding protein in patients with liver cirrhosis. AB - The recently characterized GH-binding protein (GH-BP) has an amino acid sequence identical to the extracellular domain of the GH receptor. Serum GH-BP reflects the amount of GH receptors, and the liver seems to be their main source. To evaluate the effect of liver disease on GH-BP, 52 patients with liver cirrhosis were studied. Serum GH-BP was measured by a binding assay with dextran-coated charcoal separation. Levels of GH-BP were correlated against the clinical state, assessed by Pugh's score. The GH-BP of 31 Pugh's class A patients was 9.7 +/- 0.5%/50 microL serum, and that of 21 Pugh's class B and C patients was 7.2 +/- 0.5%/50 microL serum compared to 11.3 +/- 0.5%/50 microL serum in age-matched controls. GH-BP correlated negatively with Pugh's score and serum bilirubin, and positively with serum albumin. It did not correlate with serum liver enzymes or serum insulin-like growth factor-I. Scatchard analysis of GH binding to the GH-BP revealed similar binding affinities in Pugh's A, B, and C patients and controls. The binding capacity in cirrhosis was significantly lower than that in controls. We conclude that serum GH-BP is controlled mainly by the liver and can provide an additional measure of disease severity in liver cirrhosis. PMID- 1890153 TI - Comparison of plasma oxytocin and catecholamine concentrations with uterine activity in pregnant rhesus monkeys. AB - Pregnant rhesus monkeys exhibit diurnal changes in uterine activity (UA), with episodes of increased UA during the early hours of darkness. The estrogenic environment during late pregnancy serves a permissive role in the maintenance of nocturnal UA episodes and may involve myometrial interactions with oxytocin (OT) and/or alpha-adrenergic stimuli. In the present study we have used chronically catheterized pregnant rhesus monkeys to measure diurnal changes in maternal plasma OT, epinephrine, norepinephrine, and dopamine. We also determined the effects of infusing an OT antagonist (ORF 22164) and the alpha-adrenergic antagonist phentolamine on nocturnal UA episodes. Animals were exposed to a 16-h light, 8-h dark photo-period, with the hours of darkness between 2300-0700 h. Maternal plasma samples were collected at 3-h intervals for 36 h and analyzed by RIA for OT and by high performance liquid chromatography for catecholamines. Plasma OT was correlated with UA in animals that displayed nocturnal UA episodes (r = 0.76; P less than 0.01). Maximal OT concentrations occurred at 2400 h in these animals; plasma OT was higher during the hours of darkness compared to levels during the light phase (10.4 +/- 1.9 and 3.0 +/- 0.3 pmol/L, respectively; n = 4). Some animals did not display nocturnal episodes of increased UA and showed no increase in OT concentrations during the hours of darkness. Maternal plasma catecholamine concentrations were not correlated with nocturnal UA and were maximal during the light phase. Nocturnal UA was abolished within 30 min of infusion of the OT antagonist, but phentolamine infusions had no effect on nocturnal UA. We conclude that 1) changes in maternal plasma catecholamine concentrations are not involved in the generation of nocturnal UA; 2) the presence of episodes of increased UA at night results from increased maternal plasma OT concentrations; and 3) the absence of nocturnal UA in some animals can be explained by a reduced level of OT secretion. PMID- 1890154 TI - Ras oncogene mutations in benign and malignant thyroid neoplasms. AB - Current models for tumorigenesis propose that a series of genetic alterations occur during the progression from the normal cell to the malignant phenotype. Mutations in each of the three ras genes (K-ras, H-ras, and N-ras) have been identified in many human neoplasms, including thyroid cancer. In this study we examined genomic DNA from benign and malignant thyroid neoplasms for mutations that are known to activate the ras oncogenes (codons 12, 13, and 61). DNA from frozen surgically excised tissue (n = 8) and from formalin-fixed paraffin embedded tissue (n = 30) was amplified by the polymerase chain reaction and screened for mutations using oligonucleotide-specific hybridization. No mutations were identified in follicular adenomas (n = 9). In follicular carcinomas, 2 of 14 tumors contained mutations (N-ras 61, Gln to Arg), and both of these patients had bone metastases. One of 15 papillary carcinomas had a ras mutation (H-ras 12, Gly to Ser). In contrast to other studies, we found that ras mutations are relatively uncommon in both benign and malignant thyroid neoplasms. Studies of larger numbers of tumors and comparisons of different patient populations will be required to assess a possible association of mutations in N-ras 61 with clinically aggressive follicular cancer. PMID- 1890155 TI - Dihydrospirorenone, a new progestogen with antimineralocorticoid activity: effects on ovulation, electrolyte excretion, and the renin-aldosterone system in normal women. AB - Dihydrospirorenone (DHSP; 6 beta,7 beta,15 beta,16 beta-dimethylen-3-oxo-17- alpha-pregn-4-en-21,17-carbolacton) is an aldosterone antagonist 8 times as potent as spironolactone in the rat. It is also a progestogen that suppresses ovulation in normal women at a daily dosage of 2 mg. The effects of this dosage on the renin-aldosterone system and sodium and potassium balances were investigated in two experiments. In study I, 12 healthy women received a diet with 100 mmol sodium and 60-70 mmol potassium per day from days 3-13 of their normal menstrual cycles. Six women took 2 mg DHSP; 6 others received placebo from days 8-13 of the cycle. Sodium excretion in the DHSP group rose from a mean of 79 to 98.5 +/- 8.3 mmol/day during medication. Placebo had no effect. The difference between average sodium excretion rates in subjects treated with DHSP or placebo was close to significance (P = 0.053). Potassium excretion did not change. Weight loss was slightly greater after DHSP than placebo treatment. PRA and plasma and urinary aldosterone rose significantly during DHSP medication. In study II, 12 women on a free diet were studied during a control and a treatment cyle. From days 5-25 of the second cycle, they took 2 mg DHSP (n = 6) or 1 mg cyproterone acetate. Both compounds suppressed ovulation and the rise in progesterone. During cycle 1, sodium excretion, PRA, and aldosterone were higher in the luteal than in the follicular phase, probably due to an antialdosterone effect of progesterone. DHSP reversed this pattern of natriuresis by inducing a significant early natriuresis and a rise in PRA and aldosterone. Cyproterone acetate only abolished differences in natriuresis between the follicular and luteal phases and the rise of PRA and plasma aldosterone in the luteal phase. We conclude that DHSP may be a suitable partner of ethinyl estradiol as a constituent of an oral contraceptive, since its progestogenic and antialdosterone profile is similar to that of progesterone. Other synthetic progestogens are devoid of an antialdosterone effect. The antialdosterone effect of DHSP may help prevent sodium retention and a rise in blood pressure in susceptible women. PMID- 1890156 TI - Effects of yohimbine on human sympathetic nervous system function. AB - The alpha 2-adrenergic receptor antagonist yohimbine is often used as a neuroendocrine probe in human studies, in which it is assumed to increase plasma norepinephrine (NE) by increasing sympathetic outflow. In this study we have tested that assumption by using a radioisotope dilution technique to measure norepinephrine (NE) kinetics in arterialized plasma after administration of oral yohimbine (20 or 40 mg) or placebo to normal young men. In agreement with previous studies, we found that yohimbine causes dose-dependent increases in blood pressure, heart rate, and plasma NE. We further found that the increase in plasma NE is, in fact, due to an increase in the rate of appearance of NE into plasma and not to reduced NE clearance from plasma. In addition, we found that yohimbine causes a dose-dependent increase in plasma epinephrine, which had not been found in studies measuring catecholamines in venous plasma. We conclude that yohimbine increases plasma NE levels by increasing the rate of NE release from sympathetic nerves, and probably increases epinephrine release from the adrenals. PMID- 1890157 TI - Exaggerated early insulin release and insulin resistance in a diabetes-prone population: a metabolic comparison of Pima Indians and Caucasians. AB - Pima Indians have the highest reported prevalence rate of noninsulin-dependent diabetes mellitus (NIDDM) in the world, so that metabolic comparisons with caucasians, who have a much lower rate, should provide insights into the pathogenesis of NIDDM. We have compared 81 caucasians with 211 Pima Indian nondiabetic subjects similar in age, sex, degree of obesity, and glucose tolerance. During a hyperinsulinemic euglycemic clamp at physiological insulin concentrations, Pima Indians were 17% more insulin resistant than caucasians after accounting for any differences in degree of obesity (P less than 0.0001). During oral glucose tolerance testing, mean plasma insulin concentrations were 33% higher in the Pimas (P less than 0.0001), but these differences were largely explained by the greater insulin resistance in the Pimas. Insulin clearance did not differ between the races. However, early insulin responses were exaggerated in the Indians and not explained by insulin resistance. After accounting for differences in insulin action, plasma insulin concentrations in Pima Indians were 50% higher than those in caucasians 3-5 min after iv glucose (P less than 0.0001), 38% higher 10 min after the end of a meal (P less than 0.0001), and 20% higher 30 min after an oral glucose load (P less than 0.006). These data suggest that in addition to insulin resistance, Pima Indians have exaggerated early insulin release and either increased beta-cell mass or enhanced beta-cell sensitivity to glucose. The data argue against low or delayed insulin secretion as primary factors leading to NIDDM in Pima Indians and favor insulin resistance as the underlying and initiating cause of the disease. PMID- 1890158 TI - Pheochromocytoma with pyrexia and marked inflammatory signs: a paraneoplastic syndrome with possible relation to interleukin-6 production. AB - Pheochromocytoma can cause several paraneoplastic syndromes. We report a patient with pheochromocytoma who exhibited pyrexia and marked inflammatory signs along with an elevated serum interleukin-6 (IL-6) level. All of these abnormalities disappeared and serum IL-6 became undetectable by removal of the tumor. In addition, immunohistochemical analysis revealed the presence of IL-6 in the tumor cells. It is suggested that pyrexia and the elevation of acute phase proteins can be a paraneoplastic syndrome with pheochromocytoma, and that the elaboration of IL-6 from pheochromocytoma may play an important role in the development of the syndrome. PMID- 1890159 TI - Immunohistochemical localization of epidermal growth factor in human endometrium, decidua, and placenta. AB - Epidermal growth factor (EGF) was localized immunohistochemically in human endometrium throughout the menstrual cycle, in gestational decidua, and in first, second, and third trimester placenta using two polyclonal antihuman EGF antisera. In proliferative phase endometrium, moderate EGF immunostaining was localized to the cytoplasm of stromal cells, with absent to light staining of glandular epithelium. In the secretory phase, EGF immunostaining was intense and localized predominantly to stromal cells, particularly those surrounding spiral arterioles. There was absent to light EGF immunostaining within epithelial cells; however, there was no staining of subnuclear vacuoles. In addition, the luminal surface of exhausted secretory glands demonstrated moderate EGF immunostaining. In gestational decidua, EGF immunostaining was light to moderate in the stromal cells, but was intense in the surface epithelium. Intense EGF immunostaining was noted in the syncytiotrophoblast layer of first trimester placenta, with light to moderate staining of the cytotrophoblast. Immunostaining decreased in both layers of trophoblast as pregnancy progressed. Immunoreactive EGF is found in endometrium and trophoblast and may have a physiological role in endometrial and placental function. PMID- 1890160 TI - Insulin and glucose do not affect the glycogen content in isolated and cultured trophoblast cells of human term placenta. AB - The influence of insulin and glucose on the glycogen content of isolated trophoblast cells was measured for the first time. The cells were obtained by tryptic digestion of villous tissue from term placentae of 15 healthy women, further purified on a Percoll gradient and enriched by employing a monoclonal anti HLA class-I antibody. The cells stained intensively with PKK1 and exhibited the structural and phenotypical characteristics of intermediate and syncytiotrophoblasts. The mean glycogen content of cells cultured in Dulbecco's Modified Eagle's Medium with 5.5 mM glucose was 17.7 +/- 3.2 micrograms/mg protein, remained constant from days 1-4, and was unaltered by higher glucose concentrations (17 and 28 mM) in the medium. Between 2-5 h after a medium change, the cells contained 50% more glycogen than at the time of replacement. Short term (0-5 h) as well as long term incubations (24 h) with both pathological (10(-8) M) and physiological (10(-9) M) concentrations of insulin had no effect, with respect to either the rate of increase in glycogen or the maximum level. We conclude that the glycogen content of isolated syncytiotrophoblasts in vitro is invariant to extracellular glucose concentrations and is not regulated by insulin. This suggests that cells other than syncytiotrophoblasts and their immediate precursors account for the reported alterations of glycogen content in normal human term placenta in vitro under hyperglycemic or hyperinsulinemic conditions. PMID- 1890161 TI - A mutation in the tyrosine kinase domain of the insulin receptor associated with insulin resistance in an obese woman. AB - Insulin resistance is frequently associated with acanthosis nigricans and hyperandrogenism. In patients with type A insulin resistance, this has been shown to be due to genetic defects in insulin receptor function. However, other patients with a similar clinical syndrome have been reported to have a variant of this syndrome, in which assays of insulin receptor function were normal. We have sequenced a portion of the insulin receptor gene in one such patient, a 29-yr-old woman with obesity and insulin resistance. The patient is heterozygous for a mutation substituting isoleucine for methionine at position 1153. Met1153 is located in the intracellular domain of the receptor near the cluster of tyrosine phosphorylation sites at positions 1158, 1162, and 1163. Studies of the mutant receptor expressed in NIH-3T3 cells demonstrated that the Ile1153-mutation impairs the ability of insulin to stimulate autophosphorylation of solubilized insulin receptors. In addition, the mutation impairs the ability of insulin to stimulate receptor tyrosine kinase activity to phosphorylate an artificial substrate [poly(Glu-Tyr)]. It seems likely that this defect in receptor tyrosine kinase activity explains the defect in the ability of the patient's insulin receptors to mediate insulin action in vivo. Furthermore, this patient provides a paradigm in which genetic factors act in concert with other risk factors, such as obesity, to cause clinically important insulin resistance. PMID- 1890162 TI - Insulin-like growth factor-I as a reflection of body composition, nutrition, and puberty in sixth and seventh grade girls. AB - Large variations in nutritional intake have profound effects on the GH-insulin like growth factor-I (IGF-I) axis in children and adults, but the effect of normal variations in nutrition on IGF-I concentrations is largely unstudied, particularly during puberty. We measured serum IGF-I concentrations in 325 sixth and seventh grade girls (12.4 +/- 0.7 yr) at the beginning of a multisite school based health curriculum. The mean serum IGF-I level among the 243 girls with complete data was 573 +/- 244 micrograms/L. Pubertal stage was significantly associated with IGF-I (P less than 0.0001, by analysis of variance). Mean concentrations rose from 427 +/- 198 micrograms/L among those at the earliest pubertal stages to 639 +/- 219 micrograms/L among the mature girls. After adjusting for the association with the stage of pubertal development, serum IGF-I was not significantly associated with measures of body composition (body mass index, triceps skin fold thickness, waist/hip ratio, height, and weight). Additionally, IGF-I concentrations were not associated with nutritional intake (total calories, total protein, total fat, and total carbohydrate) or such measures of nutrition as serum iron, hemoglobin, red cell mean corpuscular volume, white cell count, and cholesterol. IGF-I concentrations, however, were significantly correlated with transferrin concentrations, another possible index of nutritional status (r = 0.29; P less than 0.0001). IGF-I is not a clinically useful index of nutritional status among normal pubertal girls. PMID- 1890163 TI - Rheumatoid factor (RF) distribution in periodontal disease. AB - This study investigated the occurrence of an autoantibody, IgM rheumatoid factor, that may result from the chronic inflammation noted in periodontal disease and rheumatoid arthritis. In order to detect IgM-RF, a biotin-avidin ELISA was developed. This assay was found to be sensitive and accurate by testing a rheumatoid arthritis population. The characteristics of this rheumatoid arthritis group were further determined, such that the total serum immunoglobulin concentrations were slightly elevated although within the normal range for IgM, IgG, and IgA; IgG antibody levels were elevated against oral microorganisms of the genus Capnocytophaga, while elevated IgM antibody levels were noted to Bacteroides species. In a population of 260 subjects of which 171 were periodontal disease patients, 16 of 171 (9.4%) were seropositive for IgM-RF, of which the predominant disease types were advanced destructive periodontitis and adult periodontitis. For comparison, a random population of seronegative periodontal disease patients was constructed that was matched for sex and approximate age to the seropositive group. The total immunoglobulin levels of the two groups were not significantly different and the means of both were slightly lower than the rheumatoid arthritis group. When the antibody profiles of the two periodontal disease populations were compared it became evident that the RF positive group showed IgM and IgG antibody that was significantly elevated to Capnocytophaga species and F. nucleatum. Therefore, the chronic inflammation associated with periodontitis appears to increase significantly the formation of IgM-RF; however, there does appear to be a relationship between IgM-RF and elevated antibody to selected oral microorganisms. PMID- 1890164 TI - Different B-cell responses to human T-cell lymphotropic virus type I (HTLV-I) envelope synthetic peptides in HTLV-I-infected individuals. AB - HTLV-I (human T-cell lymphotropic virus type I) is the retrovirus related to two distinct diseases, adult T-cell leukemia/lymphoma (ATLL) and HTLV-I-associated myelopathy (HAM). We analyzed the difference in antibody activities against the viral protein and the difference in specificities of anti-HTLV-I envelope antibodies among HTLV-I-infected individuals from the same HTLV-I-endemic area using a HTLV-I-gag-env hybrid protein and HTLV-I-env-encoded synthetic peptides as antigens, respectively. The difference in the responses of IgG anti-HTLV-I envelope antibody production among HTLV-I-infected individuals was qualitative as well as quantitative. Sera from patients with HAM showed significantly higher activities of antibodies against HTLV-I-gag-env hybrid protein than sera from other HTLV-I-infected individuals including ATLL patients. The specificities of IgG anti-HTLV-I-envelope antibodies, tested on seven synthetic envelope peptides, were directed mainly against four sites, V1E7 (residues 97-111), V1E8 (191-209), and V1E9 (268-286) on gp46 and V1E1 (342-363) on gp21. Three of these sites were shown to be immunodominant T-cell sites in mice in our previous study. Whereas patients in all categories made antibodies specific for V1E1 and V1E8, only HAM patients made antibodies to the V1E7 and V1E9 epitopes, suggesting a qualitative difference in response. Whether this difference is of pathogenetic significance is not clear.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1890165 TI - Suppression of immunoglobulin production of lymphocytes by intravenous immunoglobulin. AB - The proliferative responses and the immunoglobulin production of peripheral blood mononuclear cells to pokeweed mitogen were dose-dependently suppressed by sulfonated intravenous immunoglobulin (IVIG), polyethylene glycol-treated IVIG, pH 4-treated IVIG, or human gamma-globulin, but they were not or only slightly suppressed by human serum albumin or pepsin-treated IVIG. Moreover, the suppression of immunoglobulin production by sulfonated IVIG, polyethylene glycol treated IVIG, or pH 4-treated IVIG was seen in the cases in which B cells preincubated with IVIGs were cocultured with T cells and monocytes preincubated with or without IVIGs and in the cases in which monocytes preincubated with IVIGs were cocultured with T cells and B cells preincubated with or without IVIGs. However, in the cases in which only T cells were preincubated with IVIGs, immunoglobulin production was not suppressed. The suppression of the monocyte function by IVIGs tended to be less than the suppression of the B-cell function by IVIGs. Moreover, the suppression by IVIGs was blocked by anti-human IgG Fc. Our results suggest that IVIGs suppress the immunoglobulin production of lymphocytes through suppression of the B-cell function and the antigen presenting cell function by attachment of IVIGs to Fc receptors of B-cell membranes and antigen presenting-cell membranes. PMID- 1890166 TI - Use of dried blood spot specimens in the detection of human immunodeficiency virus type 1 by the polymerase chain reaction. AB - Dried blood spots (DBSs) constitute a potentially valuable source of material for human immunodeficiency virus (HIV) serologic and molecular testing. To facilitate molecular testing, we have adapted the polymerase chain reaction (PCR) to the detection of HIV proviral DNA in DBS samples. The method is highly reproducible, with 75 microliters of whole dried blood providing sufficient DNA for duplicate testing with three primer sets. By using DBS PCR, 66 of 69 (95.6%) seropositive at-risk individuals tested positive by at least two primer sets and 85 of 85 (100%) low-risk seronegative blood donors tested negative by all three sets of primers. The frequency of HIV DNA detection in seronegative at-risk individuals was low, with only 1 of 58 (1.7%) individuals testing positive. These results show that in a clinical environment, HIV PCR analysis of DBS specimens is specific and sensitive. The method is cost effective and presents a useful alternative to the isolation of HIV from seropositive babies with an undefined infection status. PMID- 1890167 TI - Sampling efficiency in the diagnosis of Helicobacter pylori infection and chronic active gastritis. AB - The methods and sampling procedures used in the diagnosis of Helicobacter pylori infection and chronic active gastritis were evaluated. Five biopsy specimens for bacteriological cultivation and three specimens for histological examination were obtained endoscopically from a defined area of the gastric antral mucosae of 83 patients. An increase in the number of biopsy specimens for cultivation from one to five revealed only one more H. pylori-infected patient. H. pylori was isolated from 31 of 83 patients. Three technically adequate samples for histological examination were obtained from each of 74 patients. Of these 74 patients, chronic active gastritis was diagnosed by demonstration of typical histological changes in all three specimens from each of 20 patients, in two of three specimens from each of 3 patients, and in one of three specimens from 1 patient. The results indicate that one biopsy specimen is sufficient for the isolation of H. pylori, whereas several specimens may be necessary for the histological diagnosis. Chronic active gastritis was found in four patients not infected with H. pylori; on the other hand, H. pylori was isolated from nine patients who showed no signs of chronic active gastritis in any of three samples. PMID- 1890168 TI - Evaluation of 10 methods to distinguish epidemic-associated Campylobacter strains. AB - We compared four phenotypic and six genotypic methods for distinguishing Campylobacter jejuni strains from animals and humans involved in four epidemics. Based on a comparison with epidemiologic data, the methods that correctly identified all strains in three milkborne outbreaks and one waterborne outbreak were heat-stable and heat-labile serotyping; multilocus enzyme electrophoresis (MEE); DNA restriction endonuclease analysis with BglII, XhoI, PvuII, or PstI; and Southern blot and hybridization of PvuII- and PstI-digested DNA with Escherichia coli 16S and 23S rRNA (ribotyping). Biotyping, phage typing, plasmid analysis, and probing of BglII and XhoI DNA digests with C. jejuni 16S rRNA genes failed to correctly separate one or more strains. MEE, restriction endonuclease analysis, and ribotyping were the most sensitive methods and identified nine types among the 22 strains. These methods were also capable of further distinguishing strains within the same serotype. Data from MEE were also analyzed to calculate genetic relatedness among strains. Serotyping was the most discriminating phenotypic method, with eight and seven types distinguished by the heat-stable and heat-labile methods, respectively. MEE and ribotyping had several advantages over the other methods because they measure relatively stable and significant chromosomal differences and are applicable to other species and genera. These methods, however, are complex and not easily quantified; they are currently limited to specialized laboratories. When antisera are available, serotyping appears to be an effective and more practical approach to the identification of epidemic-related strains. PMID- 1890169 TI - Detection of Helicobacter pylori by using the polymerase chain reaction. AB - A 1.9-kb cloned fragment of chromosomal DNA randomly selected from a Helicobacter pylori cloned library was evaluated as a potential probe. The probe detected 19 of 19 H. pylori strains and yielded a specificity of 98.7% when tested against 306 other bacterial strains representing 32 different species. False-positive results with non-H. pylori strains were due to the presence of contaminating vector sequences. A polymerase chain reaction (PCR) assay was developed by using 20-base oligonucleotide primers homologous to a portion of the 1.9-kb fragment. The PCR assay amplified a 203-nucleotide-pair product which was analyzed by agarose gel electrophoresis and Southern hybridization by using a third 20-base 32P-labeled oligonucleotide complementary to a region of DNA between the primers. The PCR assay was 100% sensitive, detecting all 35 H. pylori strains tested, and did not amplify sequences in several closely related species. The assay was sensitive for as little as one copy of the cloned plasmid DNA or 100 H. pylori bacterial cells. To evaluate the PCR assay for clinical samples, gastric biopsy and aspirate specimens were tested by PCR, and the results were compared with those of microbiologic culture and histologic examination. In fresh biopsy specimens, H. pylori sequences were detected by PCR in 13 of 14 (93%) positive tissues and 0 of 19 negative tissues. In gastric aspirate specimens, 11 of 13 (85%) positive tissues were positive by PCR. H. pylori DNA was detected in 1 of 14 aspirate specimens negative by culture, histology, and PCR of the accompanying biopsy tissue. PCR is a rapid, accurate, and sensitive method for the detection of H. pylori. PMID- 1890170 TI - Isolation of a strain-specific Entamoeba histolytica cDNA clone. AB - Entamoeba histolytica is an intestinal parasite causing significant morbidity and mortality worldwide. More tools are needed to understand the epidemiology and molecular pathogenesis of amebiasis. A cDNA library was constructed by using poly(A)+ RNA isolated from an axenic strain of E. histolytica, HM1:IMSS, which expresses a pathogenic isoenzyme pattern (zymodeme). Differential screening of the library yielded a strain-specific 3' polyadenylated cDNA clone, C2, possessing nine 26-nucleotide tandem repeats. RNA and DNA transfer blot analysis of four axenic strains of E. histolytica possessing the same pathogenic zymodeme revealed that the gene is present and expressed in pathogenic E. histolytica HM1:IMSS and 200:NIH but is not present in pathogenic strains HK-9 and Rahman. In addition, Southern blot analysis using the C2 clone showed heterogeneity of genomic organization between HM1:IMSS and 200:NIH. DNA dot blot hybridization analysis demonstrated that cDNA clone C2 was also able to distinguish axenically cultured E. histolytica strains possessing pathogenic zymodemes from those possessing nonpathogenic zymodemes and could detect as few as 100 amebic trophozoites. We conclude that C2 is a strain-specific E. histolytica cDNA clone that, in conjunction with other E. histolytica-specific probes, could serve as a useful epidemiologic tool. PMID- 1890171 TI - Molecular probe for identification of Trichomonas vaginalis DNA. AB - Trichomoniasis is one of the most widespread sexually transmitted diseases in the world. Diagnosis can be achieved by several methods, such as direct microscopic observation of vaginal discharge, cell culture, and immunological techniques. A 2.3-kb Trichomonas vaginalis DNA fragment present in strains from diverse geographic areas was cloned and used as a probe to detect T. vaginalis DNA in vaginal discharge by a dot blot hybridization technique. This probe was specific for T. vaginalis DNA. It recognized strains from two regions in Italy (Sardinia, Piemonte) and from Mozambique (Africa). In addition, our probe did not cross react with bacterial (Escherichia coli, Enterococcus spp., group B streptococci, Gardnerella vaginalis, Neisseria gonorrhoeae, Chlamydia trachomatis, and Lactobacillus spp.), viral (herpes simplex virus type 2), fungal (Candida albicans), protozoan (Entamoeba histolytica, Giardia lamblia, Plasmodium falciparum, Leishmania major, and Leishmania infantum), or human nucleic acids. The probe reacted with Pentatrichomonas hominis and Trichomonas foetus. The limit signal recognized by our probe corresponded to the DNA of 200 T. vaginalis isolates. The 2.3-kb probe was used in a clinical analysis of 98 samples. Of these, 20 samples were found to be positive both with the probe and by cell culture, and only 14 of these were positive by a standard wet mount method. PMID- 1890173 TI - Chronic conjunctivitis caused by oral anaerobes and effectively treated with systemic metronidazole plus amoxicillin. AB - In this study, we report on a case of refractory, unilateral anaerobic conjunctivitis. The predominant anaerobic flora consisted of Prevotella intermedia (formerly Bacteroides intermedius) and Peptostreptococcus micros. By using the technique of restriction endonuclease fingerprinting of genomic DNA, it was shown that the P. intermedia likely originated from the oral cavity. Topically applied antibiotics had failed to suppress the infection in the past. Successful treatment was achieved after systemic administration of metronidazole plus amoxicillin. PMID- 1890172 TI - Serotyping of Chlamydia psittaci isolates using serovar-specific monoclonal antibodies with the microimmunofluorescence test. AB - A panel of 10 serovar-specific monoclonal antibodies that could distinguish 10 distinct serovars of Chlamydia psittaci was prepared. The panel included one monoclonal antibody to each of the 10 serovars. Monoclonal antibodies were selected for their specificity in the indirect microimmunofluorescence test. Each of the monoclonal antibodies had a titer of 1:1,280 or higher to the homologous strain, with only two showing any cross-reactivity at a dilution of 1:10. Chlamydial antigen derived from organisms growing in tissue culture of one well of a 96-well multiwell dish was usually sufficient for the serotyping of an isolate. Infected yolk sac preparations were also suitable for serotyping. The panel of monoclonal antibodies was used to serotype 55 mammalian and avian strains. All except five of the strains were successfully serotyped; these five strains are presumed to represent at least two additional serovars. The use of a panel of monoclonal antibodies in the indirect microimmunofluorescence test provides a rapid and reliable method for serotyping new isolates. Monoclonal antibodies to new serovars can easily be added to the panel. PMID- 1890175 TI - Identification of Staphylococcus species and subspecies with the MicroScan Pos ID and Rapid Pos ID panel systems. AB - The accuracies of the MicroScan Pos ID and Rapid Pos ID panel systems (Baxter Diagnostic Inc., MicroScan Division, West Sacramento, Calif.) were compared with each other and with the accuracies of conventional methods for the identification of 25 Staphylococcus species and 4 subspecies. Conventional methods included those used in the original descriptions of species and subspecies and DNA-DNA hybridization. The Pos ID panel uses a battery of 18 tests, and the Rapid Pos ID panel uses a battery of 42 tests for the identification of Staphylococcus species. The Pos ID panel has modified conventional and chromogenic tests that can be read after 15 to 48 h of incubation; the Rapid Pos ID panel has tests that use fluorogenic substrates or fluorometric indicators, and test results can be read after 2 h of incubation in the autoSCAN-W/A. Results indicated that both MicroScan systems had a high degree of congruence (greater than or equal to 90%) with conventional methods for the species S. capitis, S. aureus, S. auricularis, S. saprophyticus, S. cohnii, S. arlettae, S. carnosus, S. lentus, and S. sciuri and, in particular, the subspecies S. capitis subsp. capitis and S. cohnii subsp. cohnii. The Rapid Pos ID panel system also had greater than or equal to 90% congruence with conventional methods for S. epidermidis, S. caprae, S. warneri subsp. 2, S. xylosus, S. kloosii, and S. caseolyticus. For both MicroScan systems, congruence with conventional methods was 80 to 90% for S. haemolyticus subsp. 1, S. equorum, S. intermedius, and S. hyicus; and in addition, with the Rapid Pos ID panel system congruence was 80 to 89% for S. capitis subsp. ureolyticus, S. warneri subsp. 1, S. hominis, S. cohnii subsp. urealyticum, and S. simulans. The MicroScan systems identified a lower percentage (50 to 75%) of strains of S. lugdunensis, S. gallinarum, S. schleiferi, and S. chromogenes, although the addition of specific tests to the systems might increase the accuracy of identification significantly. PMID- 1890174 TI - Comparison of in vitro culture and polymerase chain reaction for detection of Borrelia burgdorferi in tissue from experimentally infected animals. AB - A polymerase chain reaction (PCR) was developed for identification of Borrelia burgdorferi in biological specimens. The diagnostic efficiency was compared with that of in vitro culture. A primer set specifying a 791-bp DNA fragment of the B. burgdorferi B31 flagellin gene was used. Amplified DNA sequences were analyzed by agarose gel electrophoresis, and the identity of amplified DNA was confirmed by restriction enzyme cleavage and Southern blot hybridization with a 32P-labeled probe. By using purified B. burgdorferi DNA, the detection limit of the assay was approximately 0.002 pg of DNA, corresponding to one copy of the B. burgdorferi genome. By using in vitro-cultivated B. burgdorferi without prior DNA purification as the template DNA, 2 to 20 organisms could be detected. A 791-bp DNA fragment was amplified from all of 18 different B. burgdorferi strains tested, as well as from Borrelia hermsii and Borrelia anserina but not from Treponema pallidum. The efficacy of the PCR assay was evaluated on spleen, renal, and urinary bladder tissue specimens from eight experimentally infected gerbils. Specimens from the same organs were cultured in BSK medium in parallel. Of 24 organs, 21 (88%) were PCR positive and 17 (71%) were culture positive. All culture-positive specimens were also PCR positive. Compared with B. burgdorferi cultivation, PCR had at least a comparable diagnostic sensitivity, it was less laborious, and results were available within 1 to 2 days. PMID- 1890177 TI - Identification of epidemic strains of Streptococcus suis by genomic fingerprinting. AB - A natural outbreak of Streptococcus suis meningitis in two closed swine herds was studied. DNA fingerprinting, serotyping, and biochemical profiles were assessed. Multiple serotypes were recovered from these herds. In farm A, 50 S. suis strains were isolated from 330 swabs collected. Eighteen strains belonged to serotype 2, and 32 strains belonged to serotypes 3, 5, 6, 8, 9, and 11. In farm B, 16 S. suis strains were recovered from a total of 70 samples. Eight strains belonged to serotype 7 and eight belonged to serotypes 2, 3, 5, and 8. In each epidemiological situation, a single strain characterized by a distinctive restriction fragment pattern predominated among affected penmates. The epidemic serotype 2 strain was detected in farm A in weaned pigs between the ages of 5 and 7 weeks. In contrast, the pathogenic strain in farm B belonged to serotype 7 and was isolated from pigs up to 3 weeks of age. The results from both farms strongly suggest a lateral spread of these organisms. No vertical transmission could be shown in either herd. It was concluded that genomic fingerprinting is an appropriate method to distinguish outbreak isolates of S. suis from nonoutbreak strains, within the same serotype or from epidemiologically unrelated clusters of strains. PMID- 1890176 TI - Urea-induced release of heat-labile enterotoxin from Escherichia coli. AB - Urea induces the release of heat-labile enterotoxin (LT) from cells of LT producing Escherichia coli strains. Optimal conditions were defined by using the checkerboard immunoblotting system. LT release was highest when E. coli cells were incubated in 8 M urea, pH 8.0, at 37 degrees C in a water bath for 30 min. Urea was more effective than polymyxin B in inducing the release of LT antigen from E. coli; the activity of LT from urea-treated cells was seven times that of LT from polymyxin B-treated cells. Urea also increased the antigenic and biological reactivities of purified LT. This procedure is potentially applicable for the detection of LT-producing E. coli strains in the clinical laboratory. PMID- 1890179 TI - Blocking enzyme-linked immunosorbent assay for detection of antibodies to Actinobacillus pleuropneumoniae serotype 2. AB - A blocking enzyme-linked immunosorbent assay (ELISA), based upon a polyclonal rabbit antiserum specific to Actinobacillus pleuropneumoniae serotype 2, was developed for the detection of antibodies to A. pleuropneumoniae serotype 2 in pigs. By testing sera from pigs experimentally infected with the 11 recognized serotypes of A. pleuropneumoniae, the assay was proven to be specific for A. pleuropneumoniae serotype 2. With field sera from herds infected with A. pleuropneumoniae serotype 2, the assay was found to be more sensitive than the complement fixation test. Positive results were not observed with field sera from herds known to be free from Actinobacillus infection or with sera from two herds infected with either A. pleuropneumoniae serotype 6 or 8. The high diagnostic sensitivity and specificity of the blocking ELISA will make it useful in field diagnostic work. PMID- 1890178 TI - Identification of Anaplasma marginale long-term carrier cattle by detection of serum antibody to isolated MSP-3. AB - Rapid and accurate detection of Anaplasma marginale-infected cattle would enhance anaplasmosis control procedures and evaluation of vaccines. Current tests based on detection of antibodies in serum are not widely used for several reasons, including the occurrence of either false-positive or false-negative results. We evaluated binding of antibodies in serum to a subunit antigen isolated from A. marginale initial bodies--major surface protein 3 (MSP-3). MSP-3 was detected in lysates of eight geographically different isolates of A. marginale and purified by affinity chromatography with monoclonal antibody AmG75C2. Antibodies from cattle infected with any of five geographically different isolates of A. marginale reacted in immunoblots with MSP-3. Sera from uninfected cattle and cattle infected with another rickettsial organism and two hemoprotozoal organisms failed to react with MSP-3. Six carrier cattle infected with the Florida isolate of A. marginale had antibody titers to MSP-3 ranging from 10(3) to 10(6) during a 5-year evaluation period. Since specific antibodies to isolated MSP-3 persist in high titers in long-term carrier cattle sera and MSP-3 is common among A. marginale isolates, it is recommended as a subunit antigen for an anaplasmosis test. PMID- 1890180 TI - Detection of human immunodeficiency virus type 1 by using the polymerase chain reaction and a time-resolved fluorescence-based hybridization assay. AB - The polymerase chain reaction (PCR) has many potential applications in the field of nucleic acid diagnostics. In particular, it has been successfully applied to the detection of pathogens present in low copy numbers such as the human immunodeficiency virus type 1. Here we describe a time-resolved fluorescence based hybridization assay which, combined with the PCR, offers an extremely sensitive method for the detection of nucleic acids. In this assay format, the PCR is run by standard procedures and the subsequent hybridization reaction is carried out in solution by using two oligonucleotide probes, one biotinylated and one labeled with europium (Eu3+). The sandwich hybrids are then collected onto a streptavidin-coated microtitration well, and the bound Eu3+ is measured in a time resolved fluorometer. This assay is rapid, user friendly, and quantitative and lends itself to automation. The application of this assay to the detection of human immunodeficiency virus type 1 is described. PMID- 1890181 TI - Serological follow-up of patients involved in a localized outbreak of leptospirosis. AB - Eighteen patients involved in a localized outbreak of leptospirosis were subjected to a serological follow-up study over a 5-year period. Four distinct sets of sera from all patients and a fifth sample obtained from 10 of them were examined by the microscopic agglutination test (MAT) for demonstration of leptospiral antibodies. The test was carried out by using live leptospires from reference strains of 17 Leptospira interrogans serovars known to occur in Italy. In all cases, the highest titers of agglutinins were recorded against one or more of the three Australis group serovars tested (australis, bratislava, and lora). The highest antibody levels were reached soon after the acute phase of infection in some patients but only after some months in others. Titers then tended to recede with varying rapidity, but titers against the Australis group serovars were still detectable in some patients after 5 years. Coagglutinins against serovars of other serogroups were detected, generally at low levels, in the early sets of sera of most patients, but tended to disappear in the late-set sera. Specific immunoglobulin M (IgM) and IgG against the three Australis group serovars were determined in most serum samples from 16 patients by solid-phase enzyme immunoassay (EIA). In general, EIA titers were considerably lower than MAT titers, but there was a certain patient-to-patient variability in both the IgM/IgG ratio and the evolution and persistence of the two immunoglobulin classes. Since all the evidence indicated that the initial outbreak from a single source, the observed patient-to-patient variability in the progress of both MAT and EIA titers appeared to be attributable to factors inherent in the individual patients. Cross agglutination absorption tests, aimed at retrospectively determining to which of the Australis group serovars the outbreak-specific infecting strain belonged, were performed with six serum samples from different patients. Most absorbed sera seemed to originate from an australis or lora infection, but it was not possible to discriminate conclusively between the two serovars. PMID- 1890182 TI - Pulsed field electrophoresis of genomic restriction fragments for the detection of nosocomial Legionella pneumophila in hospital water supplies. AB - Ten Legionella pneumophila strains isolated from different sources were analyzed according to their restriction fragment patterns obtained by cleavage of genomic DNA with NotI and SfiI and separation by pulsed field electrophoresis. Three L. pneumophila isolates from a nosocomial outbreak in Lubeck (Germany) and three other L. pneumophila strains independently isolated from a water tap located in the care unit where the patients were hospitalized exhibited identical restriction fragment profiles. Therefore, we concluded that these environmental specimens were the source of the Legionnaires disease. Another two isolates from patients and two strains from the environment, all unrelated to the outbreak described, showed different cleavage patterns. PMID- 1890184 TI - Egg yolk emulsion agar, a new medium for the cultivation of Helicobacter pylori. AB - We developed a new agar, egg yolk emulsion (EYE) agar, for cultivation of Helicobacter pylori. EYE agar contains Columbia agar base (Oxoid), 10% EYE (Oxoid), 1% IsoVitaleX (BBL), and 40 mg of Triphenyleteraxolium chloride (Sigma) per liter. We compared EYE agar with the following agars: (i) brain heart infusion agar-7% horse blood-1% IsoVitaleX (GDW agar; C. S. Goodwin, E. D. Blincow, J. R. Warren, T. E. Waters, C. R. Sanderson, and L. Easton, J. Clin. Pathol. 38:1127-1131, 1985), (ii) brain heart infusion agar-10% horse serum-0.2% charcoal-1% yeast extract-40 mg of triphenyltetrazolium chloride per liter (GLU agar; Y. Glupczynski, M. Labbe, and F. Thiabaumont, p. 3-6, in F. Megraud and H. Lamouliatte, ed., Gastroduodenal Pathology and Campylobacter pylori, 1989), (iii) Columbia agar with 7% lysed horse blood (D&M agar; J. C. Dent and C. A. M. McNulty, Eur. J. Clin. Microbiol. Infect. Dis. 7:555-558, 1988), and (iv) brain heart infusion agar-10% EYE-1% IsoVitaleX (BHIE agar). H. pylori CFU counts, expressed as average percentages of maximum growth, were as follows: EYE agar, 96; GDW agar. 76; BHIE agar, 57; D&M agar, 52; and GLU agar, 23. Colony counts for EYE agar were significantly higher than for GDW agar (P = 0.027), BHIE agar (P = 0.005), D&M agar (P = 0.0001), and GLU agar (P less than 0.0001). EYE agar also had higher CFU counts than two commercial chocolate media; the EYE agar count was 80%, versus 33% for BBL chocolate medium and 63% for Remel chocolate medium. PMID- 1890183 TI - Prevalence of antibody to Chlamydia pneumoniae TWAR in japan. AB - Chlamydia pneumoniae TWAR is a newly recognized Chlamydia species that is a pathogen of respiratory tract infection. To clarify the endemic status of C. pneumoniae in Japan, we evaluated the incidence of C. pneumoniae antibody in 1,330 serum samples (660 from outpatients, 600 from normal individuals, and 70 from cord blood). The antibody titer was determined by a microimmunofluorescence test by using the elementary body of C. pneumoniae TW-183 as the antigen. Immunoglobulin G antibody titers of 1:32 or higher were regarded as evidence of past infection. The detection rate of C. pneumoniae antibody rapidly increased in subjects between the ages of 4 and 7 years, reached 44% in subjects between the ages of 8 and 11 years, and was about 50% in older subjects. The rate did not differ between healthy subjects and outpatients. These results suggest that C. pneumoniae infection is highly endemic in Japan as it is in Western countries. However, the antibody prevalence was high in the low age groups in Japan compared with that in Western countries. PMID- 1890185 TI - Serratia marcescens meningitis. AB - A case of Serratia marcescens meningitis in a 66-year-old man is reported. The infection occurred 4 weeks after apparently successful otic surgery, and a nidus of infection in the middle ear was established at autopsy. This is the second case of S. marcescens meningitis following ear surgery reported in the English language literature. PMID- 1890186 TI - Reliability of two new test kits for rapid diagnosis of respiratory syncytial virus infection. AB - Two new rapid enzyme immunoassays (EIAs) for detecting respiratory syncytial virus (RSV), Directigen (Becton Dickinson Microbiology Systems) and TestPack (Abbott Diagnostics) were compared with virus isolation and direct immunofluorescence by using fresh specimens. The sensitivities of both EIAs were low (72 to 73%), but when initial specimens were used, TestPack had a high sensitivity (92%) in contrast to that of Directigen (76%). Because of its high sensitivity and specificity, TestPack can be used for diagnosis of RSV in acute disease. PMID- 1890188 TI - Serratia fonticola isolated from a leg abscess. AB - Serratia fonticola was isolated from a very large leg abscess in a patient following an accident. This is the first documented human infection due to S. fonticola. PMID- 1890187 TI - Inguinal lymphadenitis associated with Capnocytophaga bacilli. AB - Capnocytophaga organisms are capnophilic, gram-negative bacilli that have been associated with infections deriving from the flora of the oropharynx. We report a case of inguinal adenitis caused by Capnocytophaga species that probably represents sexual transmission of the pathogen. PMID- 1890190 TI - Inverse correlation in nutritionally variant streptococci between the production of bacteriolytic activity and sensitivity to a Streptococcus pyogenes bacteriocinlike inhibitory substance. AB - Nineteen strains of nutritionally variant streptococci (NVS) were tested for bacteriolytic activity and for their production of and sensitivity to streptococcal bacteriocinlike inhibitory substances (BLIS). None appeared to produce BLIS. An inverse relationship was found between the sensitivity to BLIS and the production of bacteriolytic activity against Micrococcus luteus. All but one of the 14 Streptococcus defectivus isolates were sensitive to the BLIS of S. pyogenes P5, and these isolates were nonlytic. The five S. adjacens isolates were not sensitive to any BLIS tested, and all of these isolates displayed bacteriolytic activity. Sensitivity to the BLIS of S. agalactiae P3 separated the nonlytic S. defectivus strains into two categories. PMID- 1890191 TI - Neopterin in diagnosis of human immunodeficiency virus infection in infants. PMID- 1890189 TI - Immunologic characterization and specificity of three monoclonal antibodies against the 58-kilodalton protein of Legionella pneumophila. AB - Three monoclonal antibodies against the Legionella pneumophila 58-kDa protein were produced. By using immunoblot analysis, the percentages of reactivity against 47 serogroups of Legionella representing 29 species were determined to be 80.9, 87.2, and 95.6 for monoclonal antibodies GB5BE8, GB5AF6, and CA4AF5, respectively. Specificities obtained from testing 63 heterologous organisms representing 22 genera and 46 species were 90.7, 92.2, and 95.3% for monoclonal antibodies GB5BE8, GB5AF6, and CA4AF5, respectively. No single heterologous strain was reactive with all three monoclonal antibodies. These monoclonal antibodies successfully identified all 10 clinical isolates of Legionella examined in a dot blot assay and should be excellent reagents for use in genuswide diagnostic immunoassays. PMID- 1890192 TI - WELCAN UK: its development and future. PMID- 1890193 TI - Early clinical pathologists. 4: John Hunter (1728-1793). PMID- 1890194 TI - Heterogeneity of T cell lymphoblastic leukaemias. AB - Twenty eight out of 170 consecutive cases of acute lymphoblastic leukaemia (ALL) were examined. They were of T cell origin, with the following distribution: seven (28%) cases had pre-T or prothymic features; nine (36%) cases showed early thymocytic features, six (24%) had cortical features; and three (12%) had a "mature" phenotype. The remaining three cases could not be sub-classified. A striking finding was that pre-T ALL differed from intrathymic ALL not only in the absence of both E rosettes and intrathymic differentiation antigens, but also in the expression of two non-lineage specific antigens HLA-DR and CD10. Both antigens appear in the bone marrow from the very first stages of lymphoid differentiation, implying that the origin for pre-T ALL is bone marrow. A comparison of the clinical features of pre-T and thymic ALL showed that pre-T ALL disease showed a pattern more similar to non-T ALL disease: a lower incidence of mediastinal mass, absence of extrahaematopoietic disease, lower white cell counts and haemoglobin concentrations, and a higher incidence of bone pain. No obvious difference in response to treatment was apparent. The results show that T-ALL is not only a heterogeneous immunological group but also suggest that it may have different origins: bone marrow for pre-T ALL and the thymus for thymic ALL. PMID- 1890195 TI - Immunohistological diagnosis of "plasmacytoid T cell lymphoma" in paraffin wax sections. AB - An immunohistological study of paraffin wax embedded tissue from three cases of plasmacytoid monocyte neoplasms, using a panel of antibodies which react with fixation resistant leucocyte markers, is reported. This neoplasm was found to have a distinctive antigenic profile, being negative for CD3 and elastase, but positive for CD43 and CD68. This immunological phenotype, coupled with its characteristic morphological features, should facilitate the recognition of this rare neoplasm in routinely processed tissue. Furthermore, the term "plasmacytoid monocyte sarcoma" is proposed to designate it because it is inappropriate to refer to it as a lymphoma. As all cases have been associated with a myeloproliferative disorder (usually an acute or chronic myeloid leukaemia), these tumours probably represent the accumulation in lymphoid tissue of neoplastic cells which have differentiated along the plasmacytoid monocyte pathway. PMID- 1890196 TI - Ber-ACT8: new monoclonal antibody to the mucosa lymphocyte antigen. AB - Using a newly established HTLV-1 positive T cell line as an immunogen, a new monoclonal antibody, Ber-ACT8, was produced. It reacts with in vitro activated T cells and a small subset of normal resting T cells, but not with resting B cells or any of the 29 established human permanent cell lines tested. Immunohistological analysis of a wide spectrum of human tissues showed that Ber ACT8 reactivity is restricted to a few T cells in the peripheral blood, the extrafollicular areas of lymph nodes and tonsils, and splenic red pulp. In the gut Ber-ACT8 labelled most intraepithelial T cells and up to 50% of lamina propria T cells. The antibody also immunostained T cells present in the oral and bronchial mucosa. Double labelling on splenic cells, fresh blood lymphocytes, and in vitro activated T cells showed that most Ber-ACT8 positive cells coexpressed CD8. Ber-ACT8 did not react with any of the 14 Hodgkin's lymphomas nor any of the 172 non-Hodgkin's lymphomas tested, with the exception of 10 cases of T cell lymphomas, five of which were located in the jejunum and associated with coeliac disease, and one B cell lymphoma, and most cases of hairy cell leukaemia tested. Parallel immunostainings with Ber-ACT8, anti-TCR-beta (beta F1), and anti-TCR delta showed that most Ber-ACT8 positive T cells carry the TCR of alpha beta type. Comparison of Ber-ACT8 with HML-1, B-ly7, and LF61 showed essentially the same reactivity and an identical molecular target. The molecular structure recognised seems to be a trimeric molecule with components of 150, 125 and 105 kilodaltons, with the Ber-ACT8 epitope localised on the 150 kilodalton chain. The 150 kilodalton molecule contains an 0-linked carbohydrate moiety of about 10 kilodaltons. Because of its very selective distribution, the trimeric antigen is a powerful reagent for the diagnosis of gut T cell-derived T cell lymphomas and other extranodal T cell lymphomas, as well as hairy cell leukaemia. PMID- 1890197 TI - Basement membrane proteins in the space of Disse: a reappraisal. AB - The distribution of two major basement membrane components, type IV collagen and laminin, was studied within the perisinusoidal space of Disse in normal human liver using (i) an immunoperoxidase method for light microscopy and (ii) immunogold labelling for ultrastructural localisation. Although immunoreactivity depended on the mode of tissue fixation, both proteins could be identified at this site using a panel of affinity purified antibodies. These findings indicate that these proteins are normal constituents of the perisinusoidal extracellular matrix, and refute the hypothesis that capillarization of the sinusoids in chronic liver disease results from neo-expression of laminin in the space of Disse. PMID- 1890198 TI - Breslow thickness of cutaneous malignant melanoma in paraffin wax and frozen sections. AB - Breslow tumour thickness was measured in frozen and paraffin wax sections from 21 excision biopsies of cutaneous malignant melanomas by two observers. There was no consistent variation between frozen and paraffin wax sections, with recorded differences ranging from +0.3 mm to -0.2 mm. Interobserver differences ranged from +0.4 mm to -0.2 mm. The interobserver variations exceeded the intraobserver variations, but neither were significant. These findings show conclusively that, when using high quality frozen sections, there is no significant difference between Breslow thickness measured in frozen or paraffin wax sections and therefore that frozen sections can be used to microstage melanoma. Interobserver variations seem to be a more likely source of erroneous measurements of tumour thickness. PMID- 1890199 TI - Middle ear adenoma: tumour of mixed mucinous and neuroendocrine differentiation. AB - Two cases of progressive hearing loss due to middle ear tumours are described. The histological characteristics numbered intraluminal mucin production and neuroendocrine features, as shown by argyrophilia and ultrastructural demonstration of dense core granules. These tumours have been known by many different names, reflecting the controversies relating to their presumed histogenesis and differentiation. The currently preferred designation is middle ear adenoma, and these two cases provide further evidence for dual lines of differentiation. PMID- 1890200 TI - Use of monoclonal antibodies to recognise osteoclasts in routinely processed bone biopsy specimens. AB - In decalcified (5% nitric acid) and undecalcified (glycol-methacrylate or resin embedded) routinely processed bone specimens osteoclasts against resorbing surfaces were identified with monoclonal antibodies directed against leucocyte common antigen (LCA) (PD7/26, 2B11), CD68 (KP1), and gpIIIa (Y2/51) but not against HLA-DR (CR3/43 and Ta11B5). Mononuclear cells on resorbing surfaces and occasional mononuclear cells against or near resting surfaces showed a similar pattern of reactivity. This study shows that immunohistochemistry is a sensitive and useful technique for identifying osteoclasts in routinely processed bone specimens. It also suggests a role for mononuclear cells (possibly pre osteoclasts) in bone resorption. PMID- 1890201 TI - Infections in British clinical laboratories, 1988-1989. AB - During 1988-89 this continuing survey showed 18 infections in the staff of laboratories reporting from 166 centres, representing 21,756 person-years of exposure. Shigella and other bowel infections (one caused by S typhi) predominated, affecting 11 microbiology medical laboratory scientific officers. Three shigella infections originated from quality control samples. Pulmonary tuberculosis affected four workers, including two mortuary technicians, but without detected occupational exposure to Mycobacterium tuberculosis. Other infections included one caused by Brucella melitensis. Hepatitis was not reported. The sustained low level of hepatitis is encouraging and suggests a low risk to staff of bloodborne infections such as human immunodeficiency virus. PMID- 1890202 TI - Streptococci from primary isolation plates grouped by reverse passive haemagglutination. AB - Reverse passive haemagglutination, a novel microtitre based assay, was compared with the Streptex (Wellcome UK) latex slide agglutination kit for streptococcal grouping in a diagnostic microbiology laboratory. Three hundred and fifty two extracts from 349 consecutive primary isolation plates were assayed by both methods. Reverse passive haemagglutination gave identical grouping results for 98.0% of the 345 streptococci identified by Streptex, and the kappa coefficient of agreement between the methods for all 352 extracts tested was 0.973. Cross reactions with Listeria spp seen with Streptex were not found by reverse passive haemagglutination. In the reverse passive haemagglutination method 11 streptococci could be grouped on each 96-well plate and most reactions were stable for at least 30 minutes. Reverse passive haemagglutination is more rapid to perform than latex slide agglutination when many organisms are to be grouped, and the patterns of haemagglutination are easily recognised. If the method was taken into routine use in a diagnostic laboratory, the persistence of reverse passive haemagglutination reactions would enable grouping results to be checked for quality control purposes. PMID- 1890204 TI - New sternal puncture needle. AB - The needles most commonly used for obtaining bone marrow aspirates from the sternum are the Salah and Klima needles. They were designed in the 1930s, and except for the introduction of different kinds of stops and guards there has been no change in their basic structure and design. These instruments are small, do not fit properly in the operator's hand, and the lack of a T-bar handle often makes them difficult to manoeuvre; their introduction into the sternum by twisting or rotary movement of the hand can be cumbersome. To overcome all of these disadvantages an instrument was designed which is larger, provides better grip, and offers improved maneuverability. The stilette of this aspiration needle has a domed handle which rests snugly in the operator's hand and affords operator comfort, while the specially shaped large T-bar handle at the proximal end of the needle provides adequate and firm grip and also ensures precise control during the sternal puncture procedure. PMID- 1890203 TI - Nasal, axillary, and perineal carriage of Staphylococcus aureus among women: identification of strains producing epidermolytic toxin. AB - Following two outbreaks of staphylococcal scalded skin syndrome in a maternity unit, 500 pregnant women attending an antenatal clinic were screened for carriage of epidermolytic toxin producing Staphylococcus aureus. Nasal, axillary, and perineal swabs were collected from women whose gestational ages ranged from 12-40 weeks. Isolates of S aureus were purified, phage typed, and tested for methicillin sensitivity and production of epidermolytic toxin. The results showed that 164 (33%) women carried S aureus; of these, 100 (61%) were from the nose and three (2%) from axillae, but 41 (25%) strains were isolated from the perineum alone. Screening for nasal carriage alone will therefore miss 25% of carriers. More than one strain of S aureus was identified in seven of 20 women with multiple site carriage. Three (2%) methicillin resistant strains were isolated during the survey, and five (3%) isolates produced epidermolytic toxin. Phage typing identified 63 (34%) strains as non-typable, but 50% of isolates typed either groups I, II or III, and a further 10% represented varying combinations of these and other phage groups. These results provide baseline information on S aureus in the community, and identification of methicillin resistant and toxin producing strains shows a reservoir of outbreak potential which could become relevant on hospital admission of such a carrier. PMID- 1890205 TI - HTLV-1 associated T cell lymphoma in South East Asia: case report and family study. AB - Geographic clustering of human T cell lymphoma/leukaemia virus type 1 (HTLV-1) infection is well recognised, particularly in south western Japan, parts of West and Central Africa, the south eastern United States and the Caribbean islands. Sporadic cases have been reported in many other parts of the world. The first case of HTLV-1 associated leukaemia/lymphoma (ATLL) in South East Asia is reported. Contact tracing showed a high incidence of carriers among the relatives. PMID- 1890206 TI - Treatment of acute myeloid leukaemia in a renal allograft recipient: implications of cyclosporin immunosuppressive treatment. AB - The clinical effects of cyclosporin were evaluated during cytotoxic treatment in a 61 year old man with acute myeloid leukaemia. He had required a renal transplant 18 months before presenting with acute myeloid leukaemia (FAB subtype M4). He had received cyclosporin 3.5-4.0 mg/kg daily to maintain a plasma cyclosporin concentration of 75-150 ng/ml. Cyclosporin was continued during induction chemotherapy with daunorubicin, cytarabine, and 6-thioguanine (DAT). He had fever and oropharyngeal candidiasis that was unresponsive to anti-bacterial drugs but responsive to systemic amphotericin. Bone marrow examination 14 days after chemotherapy showed complete haematological remission. Subsequently he tolerated consolidation treatment with DAT with no serious complications. Unfortunately he developed fatal septicaemia following a second consolidation with mitozantrone and cytarabine. Inhibition of P-glycoprotein activity by cyclosporin may not significantly increase the toxicity of aggressive chemotherapeutic regimens, and as benefit may be achieved by this approach further clinical evaluation is justified. PMID- 1890207 TI - Inhibition of urease activity but not growth of Helicobacter pylori by acetohydroxamic acid. AB - The in vitro effects of acetohydroxamic acid (AHA), a potent urease inhibitor, were studied to determine the effect on the urease activity and growth of 38 strains of Helicobacter pylori. AHA in concentrations of 50-1000 mg/l had a noticeably reversible inhibitory effect on the urease activity of the organism but no effect on growth. PMID- 1890208 TI - Detection of Helicobacter pylori carriers by discriminant analysis of urea and pH levels in gastric juices. AB - An alternative approach to the problems inherent in current methods for detecting Helicobacter pylori carriers--that of being generally time-consuming, expensive, and not sufficiently sensitive--was devised by using the urea concentration and pH levels of gastric juices. A linear discriminant analysis of these variables, measured in 54 patients submitted to digestive endoscopy for gastritis, provided a mathematical formula for assigning the subjects (previously classified by other standard methods) to groups of either positive or negative H pylori carriers. The results obtained showed a correct classification in 52 out of 54 cases with only one false negative and one false positive case. PMID- 1890209 TI - Acanthamoeba keratitis: experience in a non-specialist microbiology laboratory. AB - Acanthamoeba keratitis is an unusual complication of wearing soft contact lenses: a case was diagnosed by culturing corneal scrapings. Acanthamoeba are tolerant of variations in osmolarity in the culture media. Page's saline, recommended for culture agar plates, can easily be substituted with salines which are suitable for cell culture media, thereby avoiding the cumbersome manufacture of special saline. Early diagnosis as a result of successful isolation may avoid the need for keratoplasty. PMID- 1890210 TI - Statistical analysis of comparison between laboratory methods. PMID- 1890211 TI - Rectal gelatin coating: a marking tool for pathologists. PMID- 1890212 TI - Periodontal conditions in Europe. AB - The aim of the present overview is to evaluate the periodontal conditions in European populations. Study was made of a number of extensive surveys of periodontal diseases carried out in a number of European countries, primarily North West Europe. These surveys often provide considerable detail. However, international comparisons are difficult to perform because of the different methods applied. Therefore, the latest overviews of results of periodontal surveys, based on the CPITN method and stored in the WHO Global Oral Data Bank, are given for the age groups 15-19 years and 35-44 years. Based on this approach, the conclusions are as follows. Trends and prevalences in periodontal health and disease in Europe are clear, at least up to the age of 60 year. Severe periodontal destruction seems to be a limited problem, seldom leading to tooth loss before age 50 and certainly not a major cause of edentulousness before age 60. For a large majority, in most of the populations observed, the progress of periodontal destruction seems to be compatible with the retention of a natural, functioning dentition into older age. However, the periodontal problem might still be of considerable magnitude and importance as bleeding on probing is widely encountered in the younger age groups. Furthermore, 5-15% of populations affected by a serious, irreversible condition at age 40 years is high, compared with most other diseases. PMID- 1890213 TI - Factors influencing the assessment of treatment needs. AB - Epidemiologic surveys have provided data for health planning by estimating prevalence and incidence of diseases in populations. New ways of presenting epidemiologic data on periodontal diseases have changed our understanding of their extent and severity, and conversion of prevalence data into treatment need estimates has proved difficult. Furthermore, new concepts of the pathogenesis of periodontal diseases have questioned the validity of epidemiologic methods currently used. Treatment need assessments vary considerably between studies even when prevalence data from the same populations are similar. This may be due to lack of described goals for periodontal health. Various aspects of the concept of need for treatment are discussed. It is suggested that periodontal treatment need on a population level is defined as the intervention needed in order to change the existing periodontal condition to the described goal. Thus, treatment need assessments will have to include descriptive epidemiologic data as well as defined periodontal health goals. It is recommended that goals are described in terms compatible with the indicators used in the epidemiologic description of the disease status. PMID- 1890214 TI - Public health aspects of periodontal diseases in Europe. AB - There is relatively little severe periodontal disease in populations in Europe. The public health significance is therefore debateable. The fact that the costs of treating the disease are high because of the organization of dental care, qualifies it as a dental public problem. In addition, the symptoms of periodontal diseases such as bleeding, halitosis, gingival recession and tooth loss have an impact on many people, and we have sufficient information to control the common forms of the disease. The goals for dental health can be expressed in terms of health, disease, health education and health promotion and training. A reasonable objective is to achieve a rate of loss of attachment compatible with maintaining at least upper and lower shortened arches for a lifetime. 4 strategies are considered: a high risk, a population, a secondary prevention strategy or a combination of the three. A combination of the 3 is needed to achieve the objective of maintaining a functional, aesthetically and socially acceptable natural dentition for the lifespan of most people. The balance of effort should be heavily weighted towards the population strategy. If the strategy is adopted, the need for treatment will be reduced and treatment will be more successful. PMID- 1890215 TI - Periodontal diagnosis in the 1990s. AB - Clinicians are usually inclined to reduce data obtained from diagnosis to a simpler form such as "yes or no" answers in order to obtain useful parameters for daily practice. It should be realized, however, that the diagnostic process very rarely exhibits "black and white" situations. Rather the evaluation of numerous "grey levels" is imperative. The diagnostic process, therefore, remains always incomplete and inaccurate, and it represents an evaluation of probabilities rather than certainties. For this reason, the diagnostician should realize and understand the mathematical relations between the information provided by diagnostic tests and the clinical situation actually present at the time of the test. This will allow one to convert diagnostic results into therapeutic procedures with a high degree of confidence. Since results from diagnostic tests are quite often used to decide on treatment, complex data are reduced to simple dichotomy, such as presence or absence of disease, normal or abnormal conditions, etc. In order to react to diagnostic tests in an ordinal, dichotomous manner, the clinician has to choose a particular level of a test at which he initiates treatment without having the assurance that this level represents the one and only standard at which treatment has to be initiated. PMID- 1890216 TI - The onset age of periodontal destruction. AB - In the present paper, the onset age of periodontal destruction is discussed. Results of epidemiological studies have shown that with increasing age, the prevalence of periodontitis in a population increases. Data show that after the age of 40 years, the % of the population affected by periodontitis remains rather constant. If it is supposed that the incidence of periodontitis after the age of 40 is zero (no new cases), then extractions resulting in edentulousness due to periodontitis should lead to a decrease of the prevalence of periodontitis. However, after the age of 40 years, the prevalence of periodontitis remains about the same, whereas edentulousness due to periodontitis increases. This suggests that even at a relatively old age, the onset of periodontitis may occur. On the other hand, periodontal destruction has also been found in the primary dentition. Especially on the basis of family studies and studies on localized juvenile periodontitis patients, it can be supposed that in a substantial part of the population, periodontal destruction starts early in life. PMID- 1890217 TI - Decision making in periodontal therapy. The re-evaluation. AB - 7 patients completed 2 years of observation following initial therapy. Triplicate probing measurements were used to identify sites with greater than or equal to 1 mm of probing attachment change between any 2 of the following time points; immediately pre-instrumentation; immediately post-instrumentation; 3 months; 12 months and 24 months. 24% of sites lost probing attachment directly due to instrumentation. 12% of sites lost probing attachment at 24 months compared to pre-instrumentation, but over 1/3 of these lost attachment at the time of instrumentation. 47 sites lost probing attachment from post-instrumentation to 24 months. 22 of these sites were shallow buccal or lingual sites and their attachment apparatus may have remodelled. The initially deeper of these sites displayed other clinical features more consistent with inflammatory periodontitis. Sites that initially gained probing attachment due to treatment but which later lost were identified. These sites may have had a reversal of the enhanced epithelial adaption. 17 other patients were monitored over a period of 3 1/2 years and sites losing probing attachment were identified using linear analysis of regression. The diagnostic predictability of clinical signs to reveal probing attachment loss at 3 1/2 years was calculated. In general, predictability values improved with increasing time interval. Increase in probing depth, particularly if combined with a high frequency of bleeding, showed the highest predictability. The effect of therapy on probing attachment levels should be considered in the identification of sites with probing attachment loss. Persistent bleeding, combined with high residual probing depths or increase in probing depth, may be a useful adjunct to probing attachment loss in identifying diseased sites. PMID- 1890218 TI - Prosthetic reconstruction of dentitions seriously compromised by periodontal disease. AB - Dentitions seriously compromised by periodontal disease are often in need not only of cause-related periodontal therapy of high quality but also of relevant prosthetic rehabilitation. Contrary to traditional claims, clinical investigations published during the last 2 decades demonstrate that, if adequately treated and controlled, such dentitions can carry fixed, cross-arch bridges on an extremely reduced amount of periodontium, with a good long-range prognosis. It has also been shown that a markedly reduced but healthy and favourably distributed periodontium supporting such constructions can withstand occlusal forces of considerable magnitude. Another controversial topic, related to fixed bridges, involves indications and contra-indications for cantilever segments. Some clinical investigations demonstrate a markedly increased risk of failure if the fixed bridge is provided with cantilever units, while other controlled studies with defined specifications on the design of the constructions exhibit a high success rate after 8 years or more also for bridgework where 2 or 3 cantilever units are included. The force pattern along cantilever segments of both tooth-supported and implant-supported bridges has been extensively studied. The results show that the force distribution depends not only on the occlusal contact pattern and the dimensioning of the cantilever beam, but also on the type of prosthetic construction in the opposite jaw occluding with the cantilever segment. The free-standing, implant-supported bridge has recently become an important treatment modality for rehabilitation of the partially edentulous jaw, and follow-up studies demonstrate a high success rate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1890219 TI - The use of genomic DNA fingerprinting in studies of the epidemiology of bacteria in periodontitis. AB - Recent studies of microbial epidemiology emphasizing the genetic organization and distribution of organisms associated with orofacial infections have led to new insights into the possible origins of pathogenicity. Studies into genetic heterogeneity, acquisition and transmission of these organisms have been markedly advanced by the utilization of the powerful technique of genomic DNA fingerprinting. Characteristic fingerprints for each bacterial isolate can be produced by cleavage of high molecular weight genomic DNA by restriction endonucleases. It is assumed that each DNA fingerprint represents a clonal type. In this report, we review and analyze studies of the epidemiology of bacteria associated with orofacial infections with an emphasis on periodontal disease. Studies of nontypable (NT) Haemophilus influenzae associated with recurrent otitis media illustrate the utility of this technique. DNA fingerprinting clearly demonstrates genetic heterogeneity of NT H. influenzae isolates, and clonality of infection of any individual. Furthermore, DNA fingerprinting has shown that the same clonal type is seen in siblings concurrently suffering from otitis media, suggesting horizontal transmission within the family. Studies of mutans Streptococci also show extensive genetic heterogeneity and show vertical transmission of a predominant clonal type only from mother to infant, but not from father to infant. Studies of Actinobacillus actinomycetemcomitans show considerable genetic heterogeneity among monkey isolates. Thus far, three clonal types have been reported with DNA fingerprinting among isolates from periodontal patients, but additional genetic heterogeneity can be found using specific DNA fragments as probes in hybridization experiments. Intrafamilial transmission of A. actinomycetemcomitans has been demonstrated. Porphyromonas (Bacteroides) gingivalis shows extensive genetic heterogeneity and case reports suggest clonal infection of any one individual. In contrast, results with DNA fingerprinting of Eikenella corrodens, Fusobacterium nucleatum, and Bacteroides intermedius show that individuals may be infected with 2 or more clonal types. These studies point to the great potential of DNA fingerprinting for investigating the epidemiology of putative orofacial pathogens. Such studies with periodontal microorganisms will likely reveal steps in the acquisition, intraoral and person-to-person transmission, which then could possibly be inhibited or interfered with to prevent periodontal disease or its recurrence. PMID- 1890220 TI - Microbiology in the management of destructive periodontal disease. AB - This paper summarizes the rationale for the application of microbiology in the management of destructive periodontal diseases. The subgingival microbiota in patients with severe periodontitis is complex and contains high numbers of obligate anaerobic bacteria as well as facultative micro-organisms. It has become clear that major differences exist in the composition of the subgingival microflora. These differences are not only quantitative but also qualitative. Difference in plaque composition is the basis for the application of clinical microbiology in the management of periodontal disease. Several bacterial species have emerged as useful indicators for progressive periodontitis. In this respect, the importance of Actinobacillus actinomycetemcomitans, Bacteroides gingivalis and Bacteroides intermedius has been shown in a number of studies. It has become clear that A. actinomycetemcomitans is not specifically associated with the local form of juvenile periodontitis, but this micro-organism is probably also of importance in severe periodontitis in adult patients. Selection of individuals with an A. actinomycetemcomitans associated periodontitis is essential since successful treatment in these patients needs an adjunctive antibiotic therapy. Microbiological testing can be useful in patients showing a poor response to periodontal treatment (refractory periodontitis). Factors which may be responsible include poor oral hygiene, poor subgingival debridement, the patient's susceptibility and a subgingival microflora resistant to therapy. In this patient category, microbiological testing is capable of diverting continuing periodontal treatment. Furthermore, microbiology can be useful in evaluating periodontal treatment. Successful elimination of specific periodontopathic microorganisms can be used to determine recall intervals. PMID- 1890221 TI - New views on periodontal microbiota in special patient categories. AB - The microorganisms in periodontitis of special patient categories have been only partially elucidated. The periodontitis microbiota of HIV-infected individuals, cancer patients on myelosuppressive therapy, and persons with other medical disorders includes common suspected periodontal pathogens as well as enteric rods, pseudomonads, staphylococci and yeasts. Failing implants also may be associated with classical periodontal pathogens as well as primarily nonoral potential pathogens. Refractory periodontitis in systemically healthy adults can show a great variety of oral and nonoral organisms. The frequent occurrence of unusual periodontal organisms in special patient categories may be due to a weakened host response and/or usage of various chemotherapeutic regimens. The unusual organisms may contribute to progressive periodontitis and in leukemia patients may even give rise to life-threatening systemic manifestations. The primary therapeutic goal in special periodontitis patients is control of pathogens and amid the wide range of pathogenic microfloras, an effective treatment strategy should include a comprehensive microbiological analysis, especially if systemic antimicrobial therapy is contemplated. PMID- 1890222 TI - Importance of the host response in the periodontium. AB - Immunological mechanisms have been implicated in the pathogenesis of periodontal disease for over 25 years. Studies throughout the 1970s established that advanced forms of the disease were dominated by B-cells/plasma cells while early and putative stable forms of the disease were dominated by T-cells/lymphocytes. Based on these observations, a model of disease was put forward which highlighted a possible T-cell/macrophage immunoregulatory imbalance being involved in disease pathogenesis. Studies throughout the 1980s have supported such a concept although the precise nature of this imbalance remains elusive. At the same time, clinical studies have established that patient susceptibility may be of overriding importance in determining disease outcome. In this context therefore, factors which influence this susceptibility should be fundamental in determining periodontal disease activity. These factors may include genetic variation between individuals in the way in which they respond to periodontopathic bacteria upon which environmental factors would be superimposed. These environmental factors would include anything that altered the balance between the host and the parasite and may be as diverse as recent viral infections resulting in T-cell anergy or physical and mental stress. Recent studies have shown that in elite atheletes, physical stress during training and competition leads to a suppression of mucosal immunity as evidenced by a reduction in salivary IgA. The subsequent effect of these environmental factors at the level of the periodontium, however, remains to be determined. PMID- 1890223 TI - Impact of mental stress on the immune response. AB - Psychosocial factors can influence immune functions: the brain intermediates between the outside world and the inside of the body. The functional interaction between the central nervous system and the immune system is effected by 2 different pathways: the nervous "wiring system" innervating lymphoid tissues and the "soluble connection" via the neuroendocrine system. The paper reviews data from the literature regarding changes in susceptibility to infections due to stressful conditions. Emphasis is given to information regarding infection of the oral cavity and the upper respiratory tract. PMID- 1890224 TI - Periodontal disease mechanisms in immunocompromised patients. AB - Deficiency in the number and function of phagocytes is associated with gingival inflammation and periodontitis. A hereditary deficiency in membrane glycoproteins involved in granulocyte adherence causes impaired chemotaxis, reduced phagocytosis and periodontal problems. Virus infections of antigen-presenting cells interfere with immune responses and lead to seriously increased susceptibility to infections with bacteria which cause no problems in normal patients. Increased levels of IgG antibodies may limit penetration of antigens in the tissues, but at the cost of local inflammation and tissue injury. Mucosal inflammatory disease with increased local formation of IgG is more frequent in IgA deficient patients. The immunological homeostasis depends on a balance between the respective classes and subclasses of antibodies. Deficiencies in the IgA system may contribute to a disturbed balance of the humoral immune response to critical antigens from oral bacteria. A disproportional increase in IgG1 and IgG3 antibodies may persistently activate complement, stimulate the inflammatory activity and cause tissue injury. PMID- 1890225 TI - Non-plaque related periodontal lesions. An overview of some common and uncommon lesions. AB - An overview is presented of some common and uncommon non-plaque-related lesions and conditions of the periodontal tissues. Erosive lesions of the gingiva, such as lichen planus, may clinically be misdiagnosed as being the result of inflammation. Likewise, local and generalized gingival swelling may be based on non-plaque-related lesions and conditions. True leukoplakia of the gingiva is rare, but should be looked upon with suspicion. The reasons for pigmentation of the gingiva are many-fold. Especially in the maxilla, the clinician should be alert for an early malignant melanoma. A large variety of lesions may affect the periodontal bone structures, ranging from the common periapical granuloma to the rare, sometimes sclerosing, osteosarcoma. Irregular widening of the periodontal ligament and loss of the lamina dura are ominous radiographic signs. PMID- 1890226 TI - Dental bacterial plaques. Nature and role in periodontal disease. AB - Antony van Leeuwenhoek first described oral bacteria. However, not until almost 200 years later was the famous Koch postulate introduced. Since then, research has extensively been performed regarding the development and microbiology of dental plaques. In spite of the complexity of the developing flora of supragingival plaque, culture studies have shown a remarkably orderly succession of organisms. Lately, the concept of microbial specificity in the etiology of periodontal diseases has been widely suggested, i.e., that different forms of periodontal disease are associated with qualitatively distinct dental plaques. Cross-sectional and longitudinal studies of the predominant cultivable microflora reveal that only a small number of the over 300 species found in human subgingival plaques are associated with periodontal disease. Among the commonly mentioned are: Actinobacillus actinomycetemcomitans, Bacteroides gingivalis, Bacteroides intermedius, Capnocytophaga sp., Eikenella corrodens, Fusobacterium nucleatum, and Wolinella recta, as well as certain gram-positive bacteria such as Eubacterium species. Anti-infective therapy for many systemic infections equals the use of antimicrobial drugs. However, for localized infections like periodontal diseases, treatment may consist of a combination of mechanical wound debridement and the application of an antimicrobial agent. The general effectiveness of mechanical anti-infective therapy and successful oral hygiene in the management of periodontal disease is well established in the literature and has met the test of success in clinical practice for most cases of periodontitis in adults. The definition of periodontal pathogens as either opportunistic pathogens, or as exogenous pathogens carries with it significant implications.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1890227 TI - Anti-plaque agents. Rationale and prospects for prevention of gingivitis and periodontal disease. AB - Oral health surveys have shown that even in countries with established patterns of oral hygiene habits, most individuals have relatively poor gingival health. This is due to a low interest in complying with oral health procedures. A number of factors are apparent when investigating compliance to oral hygiene habits, viz only approximately 50% of the population brushes twice a day or more, brushing time is probably much too short and use of dental floss is not very prevalent. Studies of the effect of motivation on oral hygiene suggest that improvements can be achieved, but these are not maintained unless motivation is continuously reinforced. This suggests that topically applied anti-plaque agents should be used to augment mechanical plaque control. A number of product forms are available to delivery anti-plaque agents i.e., mouthrinses, dentifrices, aqueous gels, and additionally floss, chewing gum and lozenges. Any product form should provide a physically, chemically and microbiologically stable environment for the agent concerned. It should facilitate optimal bioavailability of the agents at the site of action and encourage patient compliance. Anti-plaque agents for topical administration should have the following properties: high intrinsic efficacy against a broad spectrum of oral organisms, toxicological and ecological safety, oral substantivity, no adverse reactions and good chemical stability. A number of classes of anti-plaque agents have been identified such as positively charged organic molecules, metal salts, phenols, enzymes, peroxides, sugar substitutes, fluorides and surface modifying agents. In order to achieve optimal bioavailability, the agent to be dosed should be compatible with the product form used. The 2 major product forms are rinses and dentifrices.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1890228 TI - Zinc citrate/Triclosan: a new anti-plaque system for the control of plaque and the prevention of gingivitis: short-term clinical and mode of action studies. AB - A dentifrice based upon the additive anti-plaque effects of zinc citrate and Triclosan has been developed and optimised for clinical activity. In 16-h and 4 day plaque growth inhibition studies, zinc citrate/Triclosan inhibited plaque accumulation significantly more than either agent alone. The effect on the development of gingivitis has been demonstrated in a 21-day experimental gingivitis study. ZCT/Triclosan reduced the development of gingival bleeding sites by significantly more than ZCT alone, suggesting that the system has the potential to give a gingival health benefit in a 6-month unsupervised brushing study. Zinc and Triclosan employ multiple modes of antimicrobial action and these result in reduced growth, inhibition of glucose uptake and metabolism and modified virulence of periodontal pathogens. Importantly, the effects of zinc and Triclosan are additive and complementary. Oral substantivity is a pre-requisite of any agent for anti-plaque activity in vivo. Pharmacokinetic data demonstrate that approximately 30% of the zinc and Triclosan dosed is retained immediately after brushing. Saliva decay curves indicate that Triclosan is cleared more quickly from the mouth than zinc, consistent with the physicochemical properties of these agents. Triclosan is present in plaque for at least 8 h and in the oral mucosa for at least 3 h after brushing. PMID- 1890229 TI - Dentifrices containing new agents for the control of plaque and gingivitis: microbiological aspects. AB - Antimicrobial agents have been proposed as playing an important role in controlling plaque and gingivitis. Unfortunately, a large number of potential compounds are unsuitable for use in dentifrices because they lack "substantivity", produce undesirable side-effects, or are incompatible with toothpaste ingredients. New agents that have been successfully incorporated into dentifrices include plant extracts, phenolic compounds and metal salts. Several products are currently being based on the phenol, Triclosan. Triclosan has a broad spectrum of antimicrobial activity against yeasts and oral bacteria. To enhance its clinical efficacy, Triclosan has been combined either with a co polymer or with another compatible antimicrobial agent, zinc citrate. The co polymer acts to increase the oral retention of Triclosan, and has resulted in further reductions in salivary bacterial counts in vivo. Zinc salts also have antimicrobial activity, and at low concentrations, can inhibit glycolysis and bacterial proteases. In mixed culture chemostat studies, Triclosan selectively inhibited Gram-negative periodontopathic bacteria; additive effects were obtained when zinc citrate and Triclosan were combined. In an experimental human gingivitis study, a zinc citrate/Triclosan dentifrice reduced plaque accumulation and gingivitis compared to a placebo paste; the ratio of anaerobic/aerobic bacteria and the proportions of Actinomyces species in plaque were also reduced. The prolonged use of a zinc citrate/Triclosan dentifrice neither significantly altered the ecology of supragingival plaque nor led to the selection of Triclosan resistant bacteria. The data suggest that dentifrices containing new antimicrobial agents could be of clinical relevance in the prevention and control of plaque and gingivitis. PMID- 1890230 TI - Antibacterial dentifrices. Clinical data and relevance with emphasis on zinc/triclosan. AB - The present review concerns the effect on plaque and gingivitis of some antibacterial dentifrices. The difficulties of including cationic agents in conventional dentifrice formulations are briefly discussed. The focus is on 2 recently introduced dentifrices with triclosan as the active ingredient. One aims at providing a slow release reservoir of triclosan in the oral cavity by delivering the substance dissolved in a lipophilic copolymer. 3-month results indicate a modestly improved effect on plaque and gingivitis compared to that of triclosan alone. Long-term studies are needed before conclusions on the clinical relevance can be drawn. The other dentifrice on the market utilises the principle of additive effects by combining triclosan and zinc citrate in the formulation. The combination appears to be more effective against plaque and gingivitis than either compound alone. Studies of up to 1 year duration indicate that the level of oral hygiene and gingival health obtained through an initial period of motivation and oral hygiene instruction can be maintained by regular use of the test dentifrice, while most subjects in the control group returned to pre experimental levels. Microbiological monitoring indicates no major shifts in plaque ecology nor any development of resistant bacteria, and adverse side effects have not been observed. It is concluded that the new approaches to chemical plaque control may be beneficial to the population at large, and thus of great clinical relevance. PMID- 1890231 TI - State of the art in oral implants. AB - Uncontrolled oral implant devices are still being widely used. The documentation of most oral implant systems is poorly backed up or not followed up for an adequate time period. Success rates are being quoted without reference to any defined success criteria. Frequently used oral implant designs such as the Core Vent, IMZ and Calcitek hydroxyapatite coated implants are in neither case supported by any adequate clinical reports from minimally 5-years of follow-up. Other implant systems such as the ITI, some subperiosteal designs and the Tubingen implant demonstrate well-controlled and acceptable 5-year data but are not followed up in a sufficient number or have demonstrated less good results in the 10-year evaluation. The Small transosteal staple has been adequately reported for more than 10 years of follow-up, whereas the Branemark implant is the only endosseous design that has demonstrated acceptable 15-year success rates. PMID- 1890232 TI - Implants in relation to natural teeth. AB - Osseointegrated implants are now an accepted part of the prosthetic treatment of edentulous patients. More recently, osseointegrated implants have been advocated in the treatment of partially dentate patients. The implants can be used in conjunction with natural teeth for the support of rigid prostheses. The natural tooth is supported in bone by a periodontal ligament, whereas the implant may be described as having a more intimate or ankylotic connection with the supporting bone. Different attachment mechanisms may lead to differential rates of destruction in both situations, particularly if teeth and implants are splinted together by a rigid prosthetic appliance. Also noteworthy are the possible differential rates of marginal tissue breakdown as a result of the influence of bacteria. Results of a pilot study in which marginal breakdown was induced around implants and natural teeth in beagle dogs suggest that the process of destruction proceeds more slowly in the case of implants. However, the disease process around implants may be more difficult to arrest due to conjectural problems in treating the surface of the implant using conventional techniques of periodontal treatment. From the limited data available so far, it would appear that osseointegrated implants can be used as predictably in partially dentate as in totally edentulous mouths. More research should be initiated on the potential for tissue-breakdown, and long-term maintenance of the marginal tissues around implants. PMID- 1890233 TI - The rehabilitation of oral defects by osseointegrated implants. AB - So far, preprosthetic surgery for oral defects improved prosthetic retention problems for only a limited amount of time and led to many side-effects. The alternative offered by the osseointegration technique developed by P.-I. Branemark changed the concept of preprosthetic surgery dramatically. By means of a few permucosal titanium screws, bridges or overdentures can be retained even in cases of advanced jaw bone resorption. When the latter is extreme, an autologous free bone graft fixed by means of self-tapping titanium implants can offer the necessary support for sometimes elaborate prosthetic reconstructions. The marginal bone loss around Branemark implants is very limited after a 1st year of bone remodelling, even when an autologous transplant has been used. PMID- 1890234 TI - Bone regeneration using the principle of guided tissue regeneration. AB - The biological principle of "guided tissue regeneration" (GTR) was developed for regenerating periodontal tissues, lost as a result of periodontal disease. This principle was based on the hypothesis that non-desirable types of tissue cells can be prevented from migrating into a wound by means of a membrane barrier and at the same time giving preference to those particular cells to repopulate the wound, which have the capacity to regenerate the desired type of tissue. This principle may have its application in many areas of surgery, aimed at regeneration of lost tissues. One such area is osseous surgery aimed at bone regeneration. In the present paper, a series of experiments in laboratory animals using the method of GTR for regeneration of various types of bone defects are presented as well as examples of application in humans for regeneration of jaw bone defects in conjunction with the placement of dental implants. PMID- 1890235 TI - Two systems of branching axons in monkey's retina. AB - Several monkey retinae were stained, by using the reduced silver technique, in order to analyse long-distance intraretinal connections. Long, bifurcating processes covering very large areas were identified. Morphological investigation of these processes suggest that they are members of two different systems of branching axons. The first population of these processes originates as axon collaterals from cell in the ganglion cell layer. These cells have a relatively large, elongated soma and straight, sparsely branching dendrites, stratified in the vitreal half of the inner plexiform layer. The main axon (0.6 microns average diameter) passes along the optic fibre bundles, disappearing into the optic disk, whilst its collaterals run mainly in the inner plexiform layer. A cell showing similar morphology has also been found in the ganglion cell layer of a cat retina. The second population of processes consists of very thick fibres (2.1 microns average diameter) apparently originating from the optic disk. The main branches run in the space between the optic fibre layer and the ganglion cell layer, with short, secondary processes crossing the ganglion cel layer orthogonally. Many higher-order processes originate from the second-order branches; these run almost horizontally in the inner plexiform layer. The ganglion cells generating axon collaterals may constitute an intraretinal firing synchronization system, or they may be a residual feature of retinal development. The centrifugal fibres may be related to the sensitivity control during retinal dark adaptation. PMID- 1890236 TI - Accurate prediction of Purkinje cell number from cerebellar weight can be achieved with the fractionator. AB - Purkinje cell nucleoli are used as counting units in order to obtain unbiased (fractionator) estimates of the number, N, of Purkinje neurons in adult mammalian cerebella of known weight, W. Regression analysis is then employed to establish the nature of the relationship between logN and logW. The linear regression equation defines an allometric relation that is employed to predict number in cerebella of known weight from other mammals. Predicted numbers are tested against empirical estimates. For 19 cerebella ranging in weight from 0.2 g (rat) to 113 g (human), the allometric relation between Purkinje cell number and organ weight was determined. By using this relation, the mean complement in three rabbit cerebella (average weight, 0.87 g) is predicted to be 0.63 million. This figure is confirmed by fractionator estimates made on the same three brains. The cat cerebellum should contain about 1.5-2.0 million Purkinje cells. An estimate of 1.2-1.3 million cells is to be found in the literature. Including rabbit cerebella in a refined equation yields the following relation: N = 686000W(0.695). With this refined equation, further predictions are made about the numbers likely to be found in the cerebella of the dog, goat, pig, ox, and horse. The numbers predicted for these animals must await experimental verification, but they are entirely consistent with previous suggestions that neuronal packing densities decrease with increasing brain size. PMID- 1890237 TI - Myelinated fiber regeneration after crush injury is retarded in sciatic nerves of aging mice. AB - To compare nerve regeneration in young adult and aging mice, the right sciatic nerves of 6- and 24-month-old mice were crushed at the sciatic notch. Two weeks later, both groups of mice were perfused with an aldehyde solution, and, after additional fixation, the sciatic nerves were processed so that the transverse sections of each nerve subsequently studied by light and electron microscopy included the entire posterior tibial fascicle 5 mm distal to the crush site. The same level was sectioned in unoperated contralateral nerves; these nerves served as controls. Electron micrographs and the Bioquant Image Analysis System IV were used to measure areas of posterior tibial fascicles and count the number of myelinated axons, the number of unmyelinated axons, and their frequency in Schwann cell units. In aging mice, the total number of regenerating myelinated axons was significantly reduced, but totals of regenerating unmyelinated axons in aging and young adults did not differ significantly. In aging mice, the frequency of Schwann cells that contained a single unmyelinated axon was greater, suggesting that before myelination began, Schwann cell ensheathment of axons also was slowed. After axotomy by a crush injury, the area of the posterior tibial fascicle was less than that in young adults and the distal disintegration of myelin sheath remnants also appeared to be retarded. The results indicate that responses of neurons, axons, and Schwann cells could be important in slowing the regeneration of myelinated fibers found in sciatic nerves from aging mice. PMID- 1890238 TI - From embryo to adult: anatomy and development of a leg sensory organ in Phormia regina Meigen (Insecta: Diptera). I. Anatomy and physiology of a larval "leg" sensory organ. AB - Neurons within the precursor of the adult leg, the imaginal disc, innervate a larval sense organ, Keilin's organ. Electron microscopical investigations of first instar larvae show that five dendrites end at the organ: three insert at the bases of the three hairs of the organ and two end against the cuticle, without any apparent cuticular specialization. In third instar larvae, the imaginal leg discs invaginate into the body cavity, and only four of the dendrites (the outer segments of which become greatly elongated) remain in contact with Keilin's organ. The axons of the neurons that supply Keilin's organ project into a ventral neuropile region of the central nervous system, with a pattern that resembles the projections of other larval sensilla. Electrical activity can be recorded from neurons of the imaginal disc in response to mechanical stimulation. PMID- 1890239 TI - From embryo to adult: anatomy and development of a leg sensory organ in Phormia regina, Meigen (Insecta: Diptera). II. Development and persistence of sensory neurons. AB - The imaginal leg disc of Phormia regina contains eight neurons that arise during embryogenesis. Five of the neurons are associated with Keilin's organ, and of these five, two persist to the adult fly. Two new neurons arise at about the time of pupariation and flank each of these persisting neurons, forming two triplets of cells. Both triplets can be followed throughout metamorphosis; in the late pupa they are situated anteriorly and posteriorly at the tip of the fifth tarsomere. Two triplets of cuticular specializations are found at corresponding positions in the adult fly, each consisting of two campaniform sensilla and a trichoid hair. The central member of each set of sensilla, a campaniform sensillum, is associated with the persisting cell. PMID- 1890240 TI - Calcitonin gene-related peptide (CGRP) immunoreactive projections from the thalamus to the striatum and amygdala in the rat. AB - The organization of calcitonin gene-related peptide-like immunoreactive (CGRPir) innervation of the amygdala and caudate-putamen in the rat was examined by using immunohistochemistry for CGRP combined with retrograde transport of the fluorescent dye fluoro-gold, as well as anterograde transport of Phaseoleus vulgaris leucoagglutinin (PHA-L). The lateral part of the central nucleus of the amygdala and the amygdalostriatal transition zone was densely innervated by CGRPir terminals at all anterior-posterior levels. More caudally, the lateral part of the caudate-putamen also had large numbers of CGRPir terminals. Injections of fluoro-gold into the amygdala and amygdalostriatal transition area followed by immunohistochemistry for CGRP revealed double-labeled neurons in the subparafascicular, lateral subparafascicular, and posterior intralaminar nuclei of the thalamus and peripeduncular nucleus. Injections into the caudate-putamen demonstrated double-labeled neurons in the more lateral parts of this same nuclear complex. PHA-L injections into the posterior thalamic nuclei from which the CGRPir projections arise confirmed the medial-to-lateral organization of the projections to the amygdala and striatum. The subparafascicular nucleus and the rostral portion of the lateral subparafascicular nucleus primarily projected to the medial amygdala and the amygdalostriatal transition area, while the more lateral cell groups, including the caudal part of the lateral parafascicular, posterior intralaminar, and peripeduncular nuclei projected to the lateral amygdala and the caudate-putamen. These CGRPir projections may be involved in mediating conditioned autonomic and behavioral responses to acoustic stimuli or somatosensory stimuli. PMID- 1890241 TI - Reidentification of larval interneurons in the pupal stage of the tobacco hornworm, Manduca sexta. AB - The abdominal prolegs are the primary locomotory appendages of Manduca sexta larvae. After the prolegs are lost at pupation, some of the proleg motoneurons die while the survivors are respecified to carry out different functions in the adult moth. As a first step toward investigating the process of functional respecification at the synaptic level, we searched for larval interneurons that affected the activity of proleg motoneurons, and followed these interneurons into the pupal stage. Interneurons were judged to be individually identifiable based on their effects on proleg motoneuron activity and their anatomical features. Seven larval interneurons were identified and placed in five physiological classes based on their effects on proleg motoneurons: ipsilateral excitors, contralateral excitors, ipsilateral inhibitors, contralateral inhibitors, and bilateral inhibitor-excitors. Four of the larval interneurons produced apparently monosynaptic postsynaptic potentials in proleg motoneuron. Of the five larval interneurons that were reidentified in the early pupal stage, two showed minor but consistent structural modifications from the larval stage. Interneurons that produced unitary postsynaptic potentials in larval motoneurons continued to do so in pupal motoneurons. These studies demonstrate that individually identified interneurons can be followed through the larval-pupal transformation, during the initial stages of motoneuron respecification. PMID- 1890242 TI - Stump the experts. PMID- 1890243 TI - Recurrence rates of treated basal cell carcinomas. Part 1: Overview. AB - This is the first article in a series reviewing the extensive experience of the Oncology Section of the Skin and Cancer Unit, from 1955 through 1982, with 5755 basal cell carcinomas (BCCs) treated by curettage-electrodesiccation, surgical excision, or x-ray therapy. Recurrence rates were calculated by three methods for each of the treatment modalities: 1) by the raw recurrence rate method; 2) by the "strict" 5-year recurrence rate method; and 3) by modification of the life-table method. Our analyses show that the last method best approximates the true recurrence rate. Primary (previously untreated) BCCs had a 5-year recurrence rate of 10.6% (standard error 0.6%), and previously treated BCCs had a rate of 15.4% (standard error 1.3%) (P = .0002). The greatest risk for recurrence of treated primary BCCs occurred 1 to 4 years after therapy. It is concluded that recurrence rates of primary BCCs should be reported separately from those of previously treated BCCs and that the modified life-table method is best suited to calculate 5-year recurrence rates. PMID- 1890244 TI - Multiple pilomatricomas and myotonic dystrophy. AB - Multiple pilomatricomas are rare. However, among patients with myotonic dystrophy, the occurrence is higher. The authors report a patient, to their knowledge the 11th case of multiple pilomatricomas associated with myotonic dystrophy, to emphasize that these tumors may be associated with the disease. PMID- 1890245 TI - Angiolymphoid hyperplasia with eosinophilia of the hand. A case report. AB - Angiolymphoid hyperplasia with eosinophilia is an uncommon benign vascular neoplasm manifested by multiple or solitary subcutaneous nodules, usually on or about the head of young adults. Angiolymphoid hyperplasia with eosinophilia is characterized microscopically by marked proliferation of large endothelial cells with a mixed inflammatory infiltrate consisting of lymphocytes, histiocytes, and eosinophils. This benign skin disorder may resemble an angiosarcoma both clinically and histologically. We wish to report a patient with angiolymphoid hyperplasia with eosinophilia on the palm of the hand and discuss therapeutic recommendations. PMID- 1890246 TI - Use of the argon-pumped tunable dye laser for port-wine stains in children. AB - The authors reported previously a new technique using a low power argon-pumped tunable dye laser at a wave-length of 577nm (yellow light) to treat port-wine stains in adults. The authors report their results using this same technique as a form of treatment for 92 children with facial port-wine stains. PMID- 1890247 TI - Liposculpture. 2: Evaluation of the patient for liposculpture. AB - The author discusses cannula development and patient evaluation and selection for liposculpture. The author recommends that surgeons new to liposculpture should choose their patients carefully to avoid poor cosmetic outcomes. PMID- 1890248 TI - Sunscreens. Update and review. AB - The awareness of sun-induced skin damage has increased in both the lay public and physician. Coincidentally, there has been progress in the development of new ultraviolet-(UV) radiation protecting sunscreens. In this review and update on sunscreens, sunscreen classification, UVB and UVA protection, sunscreen vehicle, and substantivity will be addressed. PMID- 1890249 TI - Lip augmentation with silicone. AB - More and more patients are coming to cosmetic and dermatologic surgeons for augmentation of their lips. Filling substances are ideal for this procedure. Silicone is the best filling substance for several reasons. Careful attention to technique and aesthetics will reward both patient and doctor. PMID- 1890251 TI - A profile of women in dental education. PMID- 1890250 TI - Excision of exposed cartilage for management of Mohs surgery defects of the ear. AB - Cartilage of the ear is often exposed during Mohs surgical procedures. Fenestration of the cartilage with a skin punch has been recommended to stimulate granulation tissue where the perichondrium has been destroyed. This article describes an alternative method--the excision of a window through the exposed cartilage, fully exposing the perichondrium on the other side of the cartilage. This promotes the rapid healing by second intention or provides a vascular bed for immediate skin grafting. Also, aggressive excision of nonviable cartilage helps prevent chondritis or perichondritis. PMID- 1890252 TI - The aging population and its impact on the future of dentistry--a symposium. PMID- 1890253 TI - The effect on the dental curriculum. PMID- 1890254 TI - Dental insurance and senior Americans. PMID- 1890255 TI - The perspectives of federal programs. PMID- 1890256 TI - A family oriented practice may be different in the 1990s. PMID- 1890257 TI - Current status of adhesive resin systems. AB - The advanced third-generation bonding agents have created excitement as they have the potential to develop effective dentin bonding. These materials have shown better bond strengths and less marginal microleakage than the previous generations of adhesives. Enamel acid etching and the new primer/adhesive systems can enhance the retention rates of resin restorations and reduce or eliminate marginal microleakage. PMID- 1890259 TI - Use of nonstimulatory peptides: a new strategy for immunotherapy? PMID- 1890258 TI - Regulation of IgE synthesis in humans: a tale of two signals. PMID- 1890260 TI - Asthma '90. Immunopharmacologic update. Course summary. Naples, Florida, February 2-4, 1990. PMID- 1890261 TI - Clinical and immunologic follow-up of patients who stop venom immunotherapy. AB - We prospectively studied 51 self-selected Hymenoptera sting-sensitive patients to determine (1) whether a minimal or optimal duration for venom immunotherapy (VIT) exists and (2) whether clinical or immunologic parameters exist that are predictive of clinical immunity after VIT was stopped. After 2 to 10 years of VIT, all patients had deliberate sting challenges (DSCs) from live insects. If DSCs were tolerated, patients voluntarily stopped VIT and returned annually for repeat venom skin tests (VSTs) and DSCs. In most patients, it was possible to monitor VST and venom-specific antibody (Ab) levels before and after VIT was stopped. One-year after VIT, VST and venom-specific IgE and IgG Ab level results were variable; 49 patients tolerated DSC, whereas two patients exhibited generalized reactions. These two patients had pre-VIT histories of grade IV field sting reactions and had received VIT for 2 years and 4 years, respectively. The short-term (1 year) risk of recurrence of clinical allergy to stings after VIT was higher in patients who had experienced grade IV field-sting reactions before VIT versus patients experiencing grade I to III reactions before VIT (2/15, 13% versus 0/36, 0%) and higher in patients who had received VIT for less than 5 years versus patients who received VIT for 5 or more years (2/20, 10% versus 0/31, 0%). We suggest that VIT should be continued for 5 years in patients with pre-VIT field-sting reactions of grade IV severity. VST and venom-specific Ab results do not reliably predict the outcome of DSC or the subsequent clinical course in individual patients stopping VIT. PMID- 1890262 TI - Identification of anti-idiotypic antibodies in the sera of ryegrass-allergic and nonallergic individuals. AB - Anti-idiotypic (Id) antibodies (Abs) are generated in the humoral response to antigen (Ag). Some of these anti-Id Abs are capable of binding to the combining site or paratope of Abs that bind Ag. These Ab2 can competitively inhibit the binding of Ab1 to Ag may trigger an Ab1 response similar to the response induced by Ag. To determine if specific Ab2 that inhibit the binding of IgE Abs to ryegrass (RG)-pollen allergens are present in the sera of RG-allergic (RGA) individuals before the initiation of allergen-specific hyposensitization with RG pollen extract, we studied sera from five RGA and four nonallergic (NA) subjects in an IgE anti-RG RAST-inhibition assay. Ab2-enriched serum fractions were prepared from these study subjects by exhaustive mixed grass-pollen affinity chromatography to remove IgE and IgG anti-RG Ab1 from whole serum aliquots containing Ab1. Unabsorbed, twice-concentrated sera were diluted to one-time concentrated sera with equal volumes of either Ab2-enriched sera without Ab1 or borate-buffered saline absorbed by mixed grass-pollen affinity chromatography. IgE anti-RG Ab1 was determined by a standard RG RAST assay. We have detected Ab2 in the sera of the RGA patients, which inhibit the binding of autologous and allogeneic IgE anti-RG to RG Ags in solid phase. Parallel RG RAST assays with sera from NA subjects demonstrated no significant inhibition. Ab2-enriched sera from some grass-allergic and some NA subjects inhibited IgE anti-RG binding found in some RGA patients' sera. We conclude that anti-Id Abs, Ab2, specific for IgE anti-RG, Ab1, are present in some RGA patients and NA individuals. PMID- 1890263 TI - The usefulness of routine screening for salivary secretory component. AB - Secretory IgA is a dimeric immunoglobulin found in association with the J chain and secretory component (SC). It is secreted into saliva and other mucosal fluids and is involved in mucosal immunity. The absence of either SC or secretory IgA may be associated with recurrent sinopulmonary infections, diarrhea, and failure to thrive. We present a retrospective study of 1262 samples from 877 patients who were screened for salivary IgA, SC, and serum immunoglobulin levels. Forty-six patients (5.2%) of those tested were found to have absent salivary SC. Although only 19 of these patients (41.3%) could be retested, all were found to have SC on repeated testing. Of the patients whose initial samples of saliva exhibited no SC, 15% (6/46) had low or absent serum IGA (less than 10 mg/dl) in contrast to 8.6% (66/769) of patients whose saliva contained detectable SC, but this was not statistically significant (chi 2 = 1.93; p greater than 0.1). There was also no correlation between serum immunoglobulin levels and the absence of SC. Because of the rarity of salivary SC deficiency, routine screening is not valuable. PMID- 1890264 TI - An examination of food hypersensitivity as a cause of increased bronchial responsiveness to inhaled methacholine. AB - To determine if food challenges could alter bronchial hyperresponsiveness, methacholine challenges were performed before and 24 hours after double-blind, placebo-controlled food challenges on 11 subjects with asthma with a history of food-induced asthma and positive skin prick tests to the suspect food. An equal number of patients demonstrated increased methacholine sensitivity after food and placebo challenges. Thus, we could not find evidence that allergic reactions to food induced bronchial hyperresponsiveness. PMID- 1890266 TI - Levels of endothelin in the bronchoalveolar lavage fluid of patients with symptomatic asthma and reversible airflow obstruction. AB - We have previously demonstrated that human bronchial smooth muscle cells possess a single class of specific binding sites for the potent bronchoconstrictive peptide, endothelin 1, and that human bronchial epithelial cells constitutively release an endothelin-like material in culture, which binds to smooth muscle cell receptors with a kinetic analogous to that observed with the authentic peptide. To evaluate the potential role of endothelin in the pathogenesis of asthma, we examined in this study the release of endothelin in the airways of six patients with asthma, both at the time when they were symptomatic and had reversible airflow obstruction and during the remission phase of the disease induced by treatment. Five normal volunteers and five patients with chronic bronchitis and airflow obstruction unaffected by bronchodilators were tested as control subjects. The release of endothelin in airway mucosa was assessed by RIA with the bronchoalveolar lavage fluid recovered during bronchoscopy. Patients with asthma had increased amounts of immunoreactive endothelin in bronchoalveolar lavage fluid than normal control subjects or subjects with chronic bronchitis (p less than 0.05) in absence of any significant alteration in the levels of circulating peptide. Treatment of patients with asthma with oral corticosteroids and inhaled beta-agonists for 15 days resulted in improvement of airflow obstruction and in more than threefold reduction in the contents of endothelin in lavage fluid. Our findings indicate that the potent bronchoconstrictive substance, endothelin, may contribute to the pathogenesis of airflow obstruction in asthma. PMID- 1890265 TI - Release of granule proteins by eosinophils from allergic and nonallergic patients with eosinophilia on immunoglobulin-dependent activation. AB - The release of eosinophil peroxidase (EPO) and eosinophil cationic protein (ECP) was evaluated after incubation of eosinophils (EOSs) from allergic subjects with the specific allergen or with anti-IgE monoclonal antibodies (MAbs). High levels of EPO could be released after addition of the specific allergen (and not unrelated ones) or anti-IgE MAb. Moreover, EPO release with the two stimuli was significantly correlated both in allergic and in nonallergic patients. In the same supernatants, another granule protein, ECP, could not be detected, suggesting a lack of correlation between EPO and ECP release after IgE-dependent stimulation. However, when EOSs with surface-IgA antibodies were incubated with anti-IgA MAb, both EPO and ECP were released. In contrast, incubation of EOSs with anti-IgG MAb induced mainly the release of ECP and not EPO. These results indicate that pharmacologically active mediators can be released by EOSs from allergic and nonallergic patients on immunoglobulin-dependent activation. The results also confirm the hypothesis of a selective release of the various granule proteins and raise the question of transduction signals delivered by the three Fc receptors (Fc epsilon R, FC alpha R, and FC gamma R) present on human EOSs. PMID- 1890267 TI - Changes in carbohydrate and lipid metabolism in children with asthma inhaling budesonide. AB - In a longitudinal study, antiasthmatic and metabolic effects of budesonide inhalations in initially high (800 micrograms/m2/day for 1 month) and subsequently lower (400 micrograms/m2/day for 4 months) dosage were evaluated in nine children with asthma, aged 5 to 10 years. The FEV1 increased significantly after high dosage (median, 96.5% versus 105.5%; p = 0.0339). After lower dosage, FEV1 was still higher than at the baseline (106% versus 96.5%; p = 0.0339). Clinically, no additional beta2-agonist was needed after 2 weeks of treatment. Serum high-density lipoprotein cholesterol increased significantly by 22% after high dosage (medians, 1.18 versus 1.44 mmol/L). A significant decline to 1.31 mmol/L was observed when the dose was reduced (overall, p = 0.0319). The treatment had no significant effect on serum total cholesterol, on serum triglycerides, on the ratio of high-density lipoprotein to total cholesterol, on the body mass index, or on glucose tolerance. The high dosage increased significantly the ratio of serum insulin to blood glucose, calculated from the areas under the incremental 2-hour curves in the glucose tolerance test (medians, 17.3 versus 23.2 mU/mmol). After lower dosage, the ratio declined significantly to 13.5 mU/mmol (overall, p = 0.0164). No significant changes were observed in plasma cortisol in the 2-hour adrenocorticotropic hormone test. The antiasthmatic effect of budesonide inhalations in a dose of 800 micrograms/m2/day for 1 month was accompanied by detectable changes in lipid and carbohydrate metabolism. These metabolic changes were reversible, and the antiasthmatic effect could be maintained by a dose of 400 micrograms/m2 for 4 months without significant systemic effects. This dose is safe and efficient in the maintenance treatment of childhood asthma. PMID- 1890268 TI - Variability in parameters of allergic bronchopulmonary aspergillosis in patients with cystic fibrosis. AB - Seventy-nine patients with cystic fibrosis (CF) were evaluated and were followed in a longitudinal, prospective fashion during a 6-year period for the development of immune parameters indicating Aspergillus fumigatus (Af) sensitization and allergic bronchopulmonary aspergillosis (ABPA). Although four patients developed frank ABPA, there was considerable variability in immune parameters in non-ABPA. Twenty-four patients became skin test positive to Af with none losing skin reactivity. Twenty-five patients developed serum precipitins to Af, whereas 12 patients lost their precipitins. Of 15 patients with an elevated total serum IgE of greater than or equal to 2 SD, five demonstrated a marked decline of at least 40%. Three of 16 patients with IgE-Af became negative, whereas eight of 27 patients lost their IgG-Af. None of these patients had received corticosteroid therapy that could have accounted for the findings. Thus, patients with CF frequently lose evidence of Af sensitivity spontaneously without corticosteroid intervention. The diagnosis of ABPA in CF should not be based solely on serology and skin test results, since at any point in time, patients with CF may demonstrate variable responses to Af. PMID- 1890269 TI - Modulation of human cutaneous mast cell responsiveness by a single, low-dose, PUVA treatment. AB - The present study was conducted to investigate whether a single administration of a relatively low dose of 8-methoxypsoralen (8-MP) with long-wave ultraviolet A (UVA) irradiation alters human skin test responses to a mast cell secretagogue, codeine, and to a vasodilator, histamine. Administration of 8-MP at a dose of 10 mg followed by UVA irradiation (1 joule/cm2) suppressed the skin flare-and-wheal response to codeine and decreased the number of visible degranulated mast cells in biopsy specimens examined histologically. UVA irradiation alone enhanced the skin wheal-and-flare response to either codeine or histamine. The inhibitory effect of 8-MP plus UVA irradiation on both wheal-and-flare responses to codeine tended to decrease, and an increasing enhancement of the skin response to histamine could be observed as the dose of 8-MP was increased from 10 to 30 mg. We postulate that (1) a single 8-MP plus UVA irradiation treatment at appropriate doses could be a potential approach to modulate the mediator-releasing properties of mast cells resident in the skin and (2) the underlying mechanisms of this inhibition is complex, probably reflecting a balance between the inhibitory effect of 8-MP plus UVA irradiation on mast cell-mediator release, enhancement of the vascular response to histamine, and direct photoactivation of resident mast cells. PMID- 1890270 TI - Anaphylactic reactions to a psyllium-containing cereal. AB - Historical data were obtained by questionnaire and telephone survey on 20 of 24 women with reported allergic reactions to a psyllium-containing cereal, Heartwise. Protein fractions from this new cereal, as well as from psyllium mucilloid and a psyllium-containing laxative, Metamucil, were extracted, quantitated, and separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Patients' sera were collected, and specific IgE and IgG antibodies to these psyllium antigens were detected by immunoblotting techniques. Of the 20 women evaluated, all but six were nurses. Eighteen (90%) of the women had historical and/or laboratory evidence of atopy. Exposures included ingestion or dispensing of psyllium-containing products. Only three women denied prior exposure to psyllium. Symptoms developed shortly after small amounts of the cereal were ingested and most commonly included moderate to severe wheezing, throat and chest tightness, and urticaria. All the women required medical therapy, 11 (55%) in an emergency room. Specific IgE and IgG antibodies to various psyllium protein fractions were documented in all the subjects. It was concluded that individuals sensitized by occupational exposure to psyllium dust are at high risk for allergic reactions to ingested psyllium-containing products. PMID- 1890271 TI - When to start, when to stop, and what to measure in venom immunotherapy: issues in allergy grand seminar, AAAI annual meeting 1990. PMID- 1890272 TI - Serum eosinophil cationic protein (ECP) in human immunodeficiency virus (HIV) infection. PMID- 1890273 TI - Spontaneous remission of common variable immunodeficiency of 20 years duration. PMID- 1890274 TI - Localized fibrosis associated with immunotherapy? PMID- 1890275 TI - In re: Cote et al. (JACI 1990;85:592-8) PMID- 1890276 TI - Guidelines for the diagnosis and management of asthma. National Heart, Lung, and Blood Institute. National Asthma Education Program. Expert Panel Report. PMID- 1890277 TI - Myocardial fibrosis in aging germ-free and conventional Lobund-Wistar rats: the protective effect of diet restriction. AB - The influences of diet restriction and germ-free environment on aging were studied in 127 male Lobund-Wistar rats ranging in age from 7 to 48 months. There was an age-related increase in collagen deposition of the heart, particularly involving the left ventricle. The degree of fibrosis was significantly less extensive in middle and old age rats (18 mo, 30 mo, 32+ mo) maintained on a restricted diet. No clear-cut influence of germ-free environment was apparent. No amyloid was detected in 175 tissue sections examined from hearts, lungs, and livers. PMID- 1890278 TI - Assessment of the role of the glucocorticoid system in aging processes and in the action of food restriction. AB - The Glucocorticoid Cascade Hypothesis of Aging and the hypothesis that food restriction retards the aging processes by preventing the development with age of hyperadrenocorticism were investigated. A longitudinal life span study of the daily concentration pattern of plasma corticosterone was conducted in male Fischer 344 rats fed ad libitum or restricted to 60% of the mean food intake of ad libitum fed rats. In another group of ad libitum fed and food-restricted rats, the influence of age on the response of plasma corticosterone levels to restraint stress was measured as was the time course of the return of plasma corticosterone to basal levels following the stress. The findings do not support the hypothesis that food restriction retards the aging processes by preventing the development of hyperadrenocorticism with advancing age. They also indicate that the Glucocorticoid Cascade Hypothesis does not describe a major aspect of the aging processes. Rather, the results suggest the possibility that a lifetime of daily periods of mild hyperadrenocorticism may, if anything, retard the aging processes. PMID- 1890279 TI - Decreased plasticity of glucoregulatory responses in aged rats: effects of chronic stress. AB - These experiments were conducted to determine the effects of age and chronic stress on the ability of rats to attenuate stimulus-induced glucose and insulin responses during repeated exposure to a mild stressor. Young (5-month) and old (21-month) Fischer 344 male rats were either exposed to intermittent sessions of an escapable footshock stress for 3 months, or to no chronic stress. Afterwards, blood samples were obtained from each rat before, during, and after the first and fourth exposure to a novel motion stimulus. Between the first and the fourth exposure to the motion stimulus a pronounced attenuation of glucose and insulin responses was seen in both groups of young rats, and in old chronically stressed rats, but not in old control animals. Thus, it appears that the adverse effects of aging on plasticity of glucoregulatory response processes were significantly diminished by exposure of the animals to periodic challenges from their external environment. PMID- 1890280 TI - Restoration of normal growth hormone responsiveness to GHRH in normal aged men by infusion of low amounts of theophylline. AB - In order to establish whether the age-related reduced growth hormone (GH) responsiveness to GH-releasing hormone (GHRH) could be improved by treatment with low amounts of theophylline, a drug mainly acting through cyclic adenosine 3', 5' monophosphate (cAMP), and calcium-mediated mechanisms, eight adult subjects (aged 20-37) and eight elderly men (aged 64-79) were tested with GHRH (50 micrograms in an iv bolus), theophylline (1.67 mg/min for 3 h), or the combination of both drugs. The GH response to GHRH was significantly lower in the older than in the younger group (mean peaks were 4.5 and 7.5 times higher than baseline, respectively). Theophylline did not change basal GH levels in any subjects and GHRH-induced GH rise in the younger group, whereas it restored normal GH responses to GHRH in the older subjects (mean peak responses were eight times higher than baseline in both groups). These data show that in elderly subjects the mechanism underlying the GHRH-induced GH secretion may be fully activated by GHRH during treatment with low amounts of theophylline. PMID- 1890281 TI - Postural change in blood pressure associated with age and systolic blood pressure. The National Health and Nutrition Examination Survey II. AB - The prevalence of postural change in blood pressure and its association with age and systolic blood pressure were examined in data from 8,574 White nondiabetic persons aged 25-74 who participated in the second National Health and Nutrition Examination Survey (1976-1980). Postural change in blood pressure was defined as a drop of 20 mm Hg or more on change from supine to seated position. In subjects on no antihypertensive medications (n = 7,316), the prevalence of postural change in blood pressure increased with older age and with higher blood pressure levels, regardless of age. However, systolic blood pressure levels also increased with age. In logistic regression models, level of supine systolic blood pressure was strongly related to postural change in blood pressure (Relative odds (RO) = 1.59, 95% confidence interval (CI) = 1.49, 1.70 for a 10 mm Hg increase in systolic blood pressure) whereas age was not related to postural change in blood pressure (RO for age = 1.07, Cl = .89, 1.19 for a 10-year increase in age). Results were similar for those medicated for hypertension. All results were unchanged by addition of health status indicators, including reports of hospitalization and number of medical conditions, to the model. These data suggest that the age related increase in the prevalence of postural hypotension previously reported may be partially explained by age-associated increases in systolic blood pressure. PMID- 1890282 TI - Risk factors for injurious falls: a prospective study. AB - We conducted a prospective study of the consequences of falls in 325 elderly community-dwelling persons, all of whom had fallen in the previous year. We contacted subjects every week for one year to ascertain falls and to determine the circumstances and consequences of falls. Only 6% of 539 falls resulted in a major injury (fracture, dislocation, or laceration requiring suture), but over half (55%) resulted in minor soft tissue injury. One in ten falls left the faller unable to get up for at least 5 minutes, and one in four falls caused subjects to limit their activities. The risk of injury per fall was about the same regardless of the number of falls a person had during follow-up. The risk of major injury was increased (age- and sex-adjusted odds ratio: 5.9, 95% confidence interval: 2.3-14.9) in falls associated with loss of consciousness compared to nonsyncopal falls. In multivariate analyses of nonsyncopal falls, the risk of major injury per fall was higher in persons having a previous fall with fracture (6.7; 2.1 21.5), a slower Trail Making B time (1.9; 1.1-3.2), and in Whites (18.4; 7.5 44.6). The risk that a nonsyncopal fall would result in minor injury (versus no injury) was increased in persons with a slower hand reaction time (1.8; 1.0-3.2) decreased grip strength (1.5; 1.0-2.3), in Whites (2.0; 1.0-3.7), in falls while using stairs and steps (2.2; 1.0-5.0), and turning around or reaching (3.5; 1.7 7.3). Our findings suggest that neuromuscular and cognitive impairment, as well as the circumstances of falls, affect the risk of injury when a fall occurs. PMID- 1890283 TI - Circadian characteristics of healthy 80-year-olds and their relationship to objectively recorded sleep. AB - Thirty-four healthy older adults (self-described "good sleepers") in their ninth decade of life (16m/18f, mean age 83.1) were compared to 30 young controls in their third decade (21m/9f, mean age 25.5) with regard to: (a) circadian and personality characteristics as measured by the Horne-Ostberg Morningness Questionnaire (HOM), Circadian Type Questionnaire (CTQ) and Eysenck Personality Inventory (EPI); (b) measures of habitual bedtime, waketime, and time in bed from a 2-week sleep diary; and (c) polysomnographic measures from a (post-adaptation) night of sleep recording in the laboratory. In almost all laboratory measures the older group slept poorly compared with the young, acquiring about one hour less total recorded sleep. The older group showed earlier habitual time of waking than the young, and showed higher (more "morning-type") scores on test instruments (HOM, CTQ-M) designed to assess morning-evening orientation. They also showed a lack of flexibility in sleep patterns (higher CTQ-Rs score) and less intersubject and intrasubject variability in habitual sleep timing compared to the young. Older subjects' morningness test scores were significantly associated with objectively measured sleep durations, with a tendency toward "morning-type" circadian orientation being associated with longer sleep. PMID- 1890284 TI - Effect of age on fever response to recombinant tumor necrosis factor alpha in a murine model. AB - Certain elderly humans show a blunted fever response to infection. A study was designed using a murine model to assess the influence of age on the febrile response to the endogenous pyrogen, tumor necrosis factor alpha (TNF alpha). Twenty (10 young: 4-6 months; 10 old: 24-28 months) BALB/c mice were injected with 50 ng of TNF alpha into the intraperitoneal space; the experiments were repeated one week later with 100 ng TNF alpha. Control animals received intraperitoneal injections of pyrogen-free phosphate buffered saline. Temperatures were measured rectally at baseline and at 10-minute intervals for 90 minutes post-injection using a thermistor probe and temperature gauge. In the majority of the time intervals following injection, the mean temperature changes of young mice were significantly higher than old mice for both 50 ng and 100 ng doses of TNF alpha. Similarly, peak temperature changes from baseline were consistently higher in young animals following injection of TNF alpha. Moreover, the peak temperature changes in young mice after 50 ng TNF alpha injection were significantly higher than those in old mice following a 100 ng injection of TNF alpha. These findings confirm that (a) TNF alpha has a role in the pathogenesis of fever; (b) aging alters significantly the febrile response; and (c) a mechanism of this age-related blunted febrile response may involve TNF alpha. PMID- 1890285 TI - On age differences in processing variability and scanning speed. AB - This investigation examined adult age differences on a recognition memory taks for order information. Experiment 1 consisted of a modified memory-scanning task in which a memory set of four letters was presented in boxes. Subjects judged whether a subsequent probe letter was or was not transposed from its original presentation position. One block of primary memory trials (i.e., no distractor task) and one block of secondary memory trials (i.e., a 10-second distractor task) were used. Experiment 2 used basically the same task, except both blocks of trials were primary memory tasks, and acoustic similarity was manipulated. A processing variability model predicted that both experiments should show distance effects (i.e., transposing letters a distance of one box should result in more errors and/or longer reaction times than a transposition of two, or three boxes) for both right and left transposition directions. However, a generalized slowing model predicted that distance effects should only occur for left transpositions (because of left-to-right scanning order). The present data supported the processing variability model but not the generalized slowing model. PMID- 1890286 TI - Attentional and perceptual contributions to the identification of extrafoveal stimuli: adult age comparisons. AB - Gerontological researchers have been cautioned that conclusions about age differences in attention may have been inferred from data that, in fact, reflected age differences in perceptual processing of stimuli falling outside the fovea (Cerella, 1985). Presumably, the experimental manipulations on which Cerella based his caution induced a broad focus of attention so that changes in perceptual processing would not be confounded with changes in attention. Experiment 1 tested this by comparing a condition similar to Cerella's with another in which attention was narrowly focused at fixation. The results replicated Cerella's findings. In addition, there were greater age differences when attention had been narrowly focused, showing that attentional effects can be separated from the effects reported by Cerella. Experiment 2 showed that age differences in extrafoveal perception could be removed by increasing the duration of the target from 200 to 2000 ms, suggesting that the perceptual deficits in older adults are due to differentially lengthened processing of stimuli outside the fovea. PMID- 1890287 TI - Recognizing and naming tunes: memory impairment in the elderly. AB - Subjects over the age of 50 listened to theme tunes of remote, recent, and frequent television programs. If they recognized the tune, they were asked for the name of the program and for as much information about the program as possible. From the responses to a subsequent questionnaire, it was possible to divide the data according to whether or not the subjects watched the programs. There was no effect of age on the recognition and naming of programs subjects never watched. For programs they watched (a true test of memory), older subjects recognized fewer tunes as familiar and were less able than younger subjects to name the programs with familiar tunes. Neither the amount of exposure nor the delay since exposure had a significant influence on the recognition and naming impairments with age. Older subjects reported less information about programs they watched than younger subjects. In multiple regression analyses, age was a better predictor of performance than measures of current cognitive ability. The results are compared with the effects of age on the recognition and naming of famous faces (Maylor, 1990a). It is argued that the studies together support the view that the information processing rate decreases with age; therefore the elderly are poor at speeded tasks, the most dramatic effects appearing for later components of sequential processes. PMID- 1890288 TI - Choice enhances performance in non-insulin dependent diabetics and controls. AB - Cognitive performance on a number of tasks is poorer in individuals with non insulin dependent diabetes mellitus (NIDDM) than in age-matched nondiabetics. In this study, diabetic and nondiabetic individuals, 55-74 years of age, learned target words, half of which were self-chosen and the remainder assigned. To evaluate susceptibility to background interference, each target was accompanied by one or more unrelated background words. On a recognition test, susceptibility to background interference appeared to be greater in diabetic individuals. The allocation of processing resources to target and background stimuli was more uniform in diabetic than in nondiabetic individuals. While choice improved recognition of target and background words for both groups, its effectiveness was attenuated in NIDDM. Choice facilitates the differentiation of target from background stimuli--a process that may reduce interference from background stimuli. PMID- 1890289 TI - Age differences in depressive symptom experiences. AB - Age differences in depressive symptom experiences were investigated in a community sample of 368 women between the ages of 51 and 92 who were administered the SCL-90 Depression and Additional Symptoms Scales. Confirmatory factor analysis was used to assess and compare depressive symptom experiences in a younger (age 51-65) and older (age 66-92) age cohort. Findings show that two somewhat different depressive syndromes underlie symptom reporting patterns, one having higher levels in the older age cohort, the other having higher levels in the younger age cohort. In addition, three more delimited forms of distress -- feelings of enervation, dysphoria, and sleep disturbances -- show higher levels among the older cohort. Implications of these findings for future research on the relation between aging and depression are discussed. PMID- 1890290 TI - Social density, stressors, and depression: gender differences among the black elderly. AB - This research examined gender differences with regard to the effects of social density and stressors upon depressive symptomatology among 600 Black elderly community residents (aged 55-85 years) of Nashville, Tennessee. The sample had more females than males and fewer married individuals. Approximately half of the males and females lived alone. Regression analyses show that poor ego and chronic medical problems were the common predictors of depression among both the males and females. Gender differences were found with regard to life events in that females tended to become more depressed as the number of events increased and as level of contact with relatives and friends decreased. Further, females with lower levels of social attachment, guidance, and reliability were more depressed. None of these social support dimensions related to depression among the males. These relationships tended to be stronger for those living alone than for those living with others. PMID- 1890291 TI - The role of time orientation in life satisfaction across the life span. AB - Relating contentment to different points in life can provide the construct of life satisfaction with an essential time orientation. The Self-Anchoring Scale was used to rate life in the present, the past (five years before), and the future (five years ahead). Subjects were the respondents of five national surveys in Israel. The findings showed an age-related configuration where progressive age was associated with declining ratings for the future, a milder decline for the present, and a relative increase for the past. In addition to rating levels, a structural modeling approach was used to explore the relative salience of these time referents, considered as indicators of the construct of life satisfaction. LISREL estimates of the indicator loadings in two related models showed the present as most salient and the past as least salient in most age groups. The salience of the past increased in later life, when that of the future did as well. The time-related construct of life satisfaction (which fit the data in all age groups) highlights the yet undetermined role of the future in the subjective well-being of the elderly. PMID- 1890292 TI - A longitudinal investigation of the factor structure of subjective well-being: the case of the Philadelphia Geriatric Center Morale Scale. AB - The purpose of this research was twofold: (a) to replicate the hierarchical factor structure of well-being with rural data; and (b) to investigate the longitudinal invariance of this factor structure. Subjective well-being was hypothesized to have a hierarchical factor structure with a second order factor, well-being, explaining variance in first order dimensions labeled agitation, lonely dissatisfaction, and attitude toward one's aging. The latent constructs were measured by items composing the PGC Scale (Lawton, 1975). Maximum likelihood confirmatory factor analysis techniques were used to test the fit of the model. Subjective well-being was investigated using a panel of older rural adults surviving a ten-year, two-wave investigation. Results of the study provided support for the hierarchical factor structure of well-being in cross-sectional analyses. This factor structure was varied across time, however. PMID- 1890293 TI - Exploratory and problem-solving consumer behavior across the life span. AB - Different cognitive functioning, social, and personality changes appear to occur systematically during the adult life span. This article synthesizes research on life span changes in order to develop age-specific models of shopping behavior. The models are tested within a naturalistic field study of shoppers. PMID- 1890294 TI - Race and the self-reported health of elderly persons. AB - This research examined race differences in the structure and measurement of six self-reports of health that are widely used in studies of elderly persons. Second order confirmatory factor analyses (LISREL) revealed race differences only in the validity of subjective interpretations of health state and in the measurement error of a chronic conditions indicator. No race differences were found in the form of the four-factor model of self-reported health. Results, interpreted within a cognitive illness-labeling framework, have implications for future race comparative health research. PMID- 1890296 TI - Centrality of the grandfather role among older rural black and white men. AB - This study examined racial differences in the centrality of the grandfather role and in the factors related to its saliency. Rural men aged 65 years or older, 48 Black and 51 White, reported on their grandchild of most contact. Multiple Classification Analysis, t-tests, and hierarchical multiple regression were used to examine two hypotheses: (a) the grandfather role would be more central to Black than to White men, and (b) factors predicting interaction with grandchildren would vary by race. Strong support was found for both. Racial differences were observed in household structure, association with grandchildren, grand-filial expectations, help given to grandchildren, and in affection for grandchildren. Similarities, however, were seen in the ranked importance of the role, in the amount of help received from grandchildren, and in grandfather grandchild consensus. The findings support a cultural rather than a structural/economic base for the grandfather role, thus validating the cultural variant perspective. PMID- 1890295 TI - Predictors of health status in middle-aged and older Mexican Americans. AB - Data from the Southwestern sample of the Hispanic Health and Nutrition Examination Survey (Hispanic HANES) were employed to investigate the association of socioeconomic variables with the health status of middle-aged (aged 45 to 59) and older (aged 60 and over) Mexican Americans. The most significant and consistent predictor of health status was employment. Less acculturated men had poorer self-assessed health; married men were more likely to have been hospitalized during the year prior to the interview, while less acculturated women were less likely to have been hospitalized (other things equal). Analysis involving interaction terms showed more significant associations in middle-aged than in older respondents, but only among men. Implications related to a selective survival thesis are discussed along with directions for future research. PMID- 1890297 TI - A multivariate comparison of the involvement of adult sons versus daughters in the care of impaired parents. AB - The purpose of this research was to explore whether gender differences in parent care (i.e., the greater participation of daughters) persisted after controlling for additional caregiver and care-receiver characteristics known to affect the provision of care. Assistance with activities of daily living (ADLs) was examined separately from assistance with instrumental activities of daily living (IADLs). A multivariate analytical framework was employed to account for the effects of a wide range of variables. Moreover, data on all of the living children (N = 13,172) of a sample of impaired elders (N = 4,371) were used, not just data on those children who were known to be providing help. Net of other caregiver and care-receiver characteristics, daughters were 3.22 times more likely than sons to provide ADL assistance and 2.56 times more likely to provide IADL assistance. Although these results are not substantively different from previous research, the methodological approach taken provides a better empirical base for estimating the effect of gender on the probability of being involved in parent care. PMID- 1890298 TI - Key relationships of never married, childless older women: a cultural analysis. AB - The key relationships of never married, childless older women, that is, those relationships described as central, compelling, enduring, or significant throughout their lifetimes, were explored in this study. Analysis of qualitative, ethnographically based interviews with 31 women indicated that the key relationships they describe fall into three classes: ties through blood, friendships, and those we label "constructed" ties (kin-like nonkin relations). We report on types of key interpersonal relationships of these women and also examine limits to these key relations, describing some strategies these women have adopted for gaining kin-like relations and the problems inherent in them for the expectation of care in later life. Theoretical work by anthropologist David Schneider concerning American kinship as a cultural system is used to explore dimensions of these relationships. PMID- 1890299 TI - Role reversals in the exchange of social support. AB - We tested the assumption that there is a role reversal in exchanges of social support: that the older one becomes, the less likely one is to send support and more likely one is to receive it. Using data from a community study in Southern California with 513 middle-aged and older respondents, the results show that both support-sending and support-receiving decline with age. The respondents report giving more support than they receive until age 85+. Controls for income and activities of daily living extend the age at which role reversal occurs, and further controls for the number of people in the social network eliminate it. Examining different types of support and different sources of support shows that similar results apply to both affective and instrumental support, but that this pattern applies more to exchanges with family members, as all forms of role reversal are less likely in exchanges with nonfamily. PMID- 1890300 TI - Home upkeep and housing quality of older homeowners. AB - Among older homeowners, successive cohorts exhibit lower levels of home upkeep. This research explores several possible sources of these age-related differences in home upkeep as well as the potential effects on the quality of the elderly population's housing. Analysis of data from the Survey of Housing Adjustments suggests that only income has sizable effects on the quantity of home upkeep conducted, and that lower upkeep appears to reflect cutbacks in discretionary, as opposed to vital repairs. PMID- 1890301 TI - Antigen-induced Fc receptor-dependent and -independent B cell desensitization. An elevation in [Ca2+]i is not sufficient and protein kinase C activation is not required for these pathways of surface IgM-mediated desensitization. AB - The interaction of an Ag ligand with its B cell surface Ig (sIg) receptor can occur via an FcR-dependent or -independent pathway. We previously found that transfected TNP-specific B cells undergo both Ca2+ signaling and desensitization upon interaction with the thymus-dependent Ag TNP-OVA. Similarly, we showed that these B cells can also be desensitized by cross-linking sIg to the Fc gamma R via the formation of an Ag-antibody bridge. Thus, Ag-specific B cells can be desensitized by two different Ag-dependent events, one mediated by Ag-sIg interaction and the other by sIg-Fc gamma R cross-linking. Inasmuch as Ag-sIg and sIg-Fc gamma R interactions lead to positive and negative signaling, it was of interest to determine whether B cell desensitization mediated by these interactions occurs by one of the well known signaling pathways in B cells. We found that Ag-induced changes in [Ca2+]i could be readily dissociated from Ag induced desensitization, indicating that a Ca(2+)-independent pathway is likely responsible for this pathway of desensitization. To determine if PKC plays a role in B cell desensitization mediated by either Ag or sIg-Fc gamma R interaction, PKC was downregulated by long term exposure to 12-O-tetradecanoylphorbol 13 acetate or inhibited by exposure of cells to staurosporine. The PKC down regulated and inhibited cells underwent similar Ag- and Fc gamma R-dependent desensitization compared to cells containing active PKC. Taken together, these data indicate that Ag-induced desensitization of B cell signaling likely involves an event(s) that occurs either upstream or independent of Ag-induced elevations in [Ca2+]i and PKC activation. PMID- 1890302 TI - Stimulation of in vitro murine lymphocyte proliferation by bacterial DNA. AB - Although DNA is generally considered to be a poor immunogen, recent evidence suggests that DNA from various species differ in their immunologic activity and that bacterial DNA, unlike mammalian DNA, can induce significant antibody responses in mice. To explore further the immunologic activities of bacterial DNA, its ability to stimulate in vitro proliferation of murine lymphocytes was tested. The stimulation of lymphocytes with highly purified ssDNA from Escherichia coli resulted in a dose-dependent response that was maximal at 48 h. Several lines of evidence indicate that DNA, rather than endotoxin contamination, induced this response: 1) LPS at doses equivalent to those detected in the DNA preparation caused significantly less proliferation than the DNA; 2) the response to DNA was insensitive to polymyxin B; 3) pretreatment of DNA with DNase completely abrogated the response; and 4) DNA induced the proliferation of cells from endotoxin-resistant C3H/HeJ mice. Furthermore, although DNA from three different bacterial species induced proliferation, mammalian DNA from three species were nonmitogenic. Depletion of T cells from lymphocytes did not reduce proliferation, suggesting that bacterial DNA directly triggered B cell proliferation. These studies provide further evidence that DNA are not uniform in their immunologic activities likely because of their content of nonconserved structural determinants. PMID- 1890303 TI - Alloreactive cytotoxic T cells recognize MHC class I antigen without peptide specificity. AB - In this report, experiments are described to differentiate between three potential models of class I MHC allorecognition, namely 1) recognition of peptide free MHC, 2) peptide-MHC-specific recognition, and 3) peptide-MHC-nonspecific recognition. Using a nucleoprotein peptide (NPP) with a sequence derived from influenza virus nucleoprotein with high affinity for Kd class I MHC molecules, it is shown that target cells rapidly become lysable by Kd-NPP self-restricted cytotoxic T (Tc) cells, and retain sufficient Kd-NPP complexes for at least 72 h. Kd-specific alloreactive Tc cells at the clonal and polyclonal level do not show decreased lysis of Kd-bearing targets in the continuous long term (48 h) presence of NPP. Kd-stimulator cells modified with NPP are able to induce potent Kd-NPP specific self-restricted Tc cells, however Kd-NPP stimulator cells do not generate Kd-NPP specific alloreactive Tc cells from CBA and B10.A (5R) mouse strains as tested by limiting dilution split clone experiments. Human cells infected with the vaccinia virus recombinant coding for the murine Kd class I MHC Ag can be lysed by murine Kd-specific alloreactive Tc cells. In addition the rate of reemergence of alloreactive and self-restricted Tc cell epitopes on virally infected target cells that had their cell-surface class I MHC Ag removed is identical. These results are consistent with model 3 namely that the majority of Tc precursor and effector cells recognize class I MHC Ag without peptide specificity. PMID- 1890304 TI - The generation of immunogenic peptides can be selectively increased or decreased by proteolytic enzyme inhibitors. AB - The ability of splenic APC and a B cell hybridoma (LS.102.9) to process and present OVA to a panel of T-T hybridomas with different fine specificities was investigated. Splenic APC process and present OVA to all the T-T hybrids. The B cell hybridoma could similarly process and present OVA to some T-T hybrids but was very inefficient in stimulating two of the T cell hybridomas. The presentation of native OVA to these two T-T hybrids was significantly increased by leupeptin. Pulsing experiments demonstrated that leupeptin acted on the APC at a step before the processed Ag was displayed on the cell surface in association with MHC molecules. Leupeptin has no effect on the presentation of OVA peptides by LS.102.9 to the T-T hybrids. Leupeptin inhibits the generation of the epitopes of OVA that LS.102.9 produces under basal conditions. We also surveyed the effect of other protease inhibitors and observed similar augmenting and inhibitory effects on the presentation of selected OVA epitopes. The augmentation of processing by a protease inhibitor indicates that in the lysosomal/endosomal compartment proteases have capacity to both generate and destroy immunogenic peptides. Our data suggest that protease inhibitors could potentially be used as immunomodulators and are discussed in terms of physiology of the lysosomal/endosomal compartment. PMID- 1890305 TI - The effects of IL-1, IL-2, and tumor necrosis factor on polymorphonuclear leukocyte Fc gamma receptor-mediated phagocytosis. IL-2 down-regulates the effect of tumor necrosis factor. AB - It has been reported that the Fc gamma R-mediated phagocytic activity of polymorphonuclear leukocytes (PMN) from patients with acute bacterial infections is markedly enhanced when compared with healthy controls. Inasmuch as several potent cytokines are known to be involved in inflammatory and infectious processes, we studied the effects of three such cytokines (IL-1 beta, IL-2, and TNF-alpha) on normal PMN Fc gamma R-mediated phagocytosis. IL-1 beta and TNF alpha both caused a significant increase in the ingestion of EIgG by adherent PMN. In combination, IL-1 beta and TNF-alpha had an additive effect, even when each was used at its optimal concentration. In contrast to the enhancing effects mediated by IL-1 beta and TNF-alpha, IL-2 alone had no significant effect on PMN phagocytosis. Notably, however, IL-2 at a concentration of 10(4) U/ml partially inhibited TNF-alpha-mediated enhancement of phagocytosis by decreasing TNF binding to the PMN cell surface. This inhibitory effect of IL-2 on TNF was reversed by anti-IL-2 antibody and mAb directed against the low affinity IL-2R (anti-Tac), whereas mAb directed against the intermediate affinity receptor (mik beta 1) had no such effect. These findings may have important physiologic implications, because patients receiving IL-2 therapy have been shown to have increased susceptibility to infection. PMID- 1890306 TI - Spontaneous activation of serum C1 in vitro. Role of C1 inhibitor. AB - The temperature and ionic strength dependence of the spontaneous activation of C1 were determined for normal human serum, and the free energy, enthalpy, and entropy of spontaneous activation were calculated. The half-life of C1 in human serum was approximately 15 h at 37 degrees C. This half-life was markedly extended by dilution with C1-depleted serum, and an extrapolated upper limit of 40 to 50 h was reached at infinite dilution. Thus, the spontaneous activation of C1 in serum appeared to involve a dilution-sensitive reaction as well as a dilution-insensitive, first order reaction. A reaction mechanism was developed combining: 1) first order spontaneous activation of C1; 2) second order, C1 catalyzed activation of C1; and 3) second order inactivation of C1 by C1 inhibitor. A steady state equation was derived from this reaction mechanism, which provided a reasonable fit to the experimental data. The equation predicts that when the C1-inhibitor concentration decreases so that the steady state condition is lost, the concentration of C1 builds up quickly, and activation of most of the C1 occurs rapidly. PMID- 1890307 TI - Occupancy of CD11b/CD18 (Mac-1) divalent ion binding site(s) induces leukocyte adhesion. AB - The group of leukocyte integrins CD11a-c/CD18 coordinate disparate adhesion reactions in the immune system through a regulated process of ligand recognition. The participation of the receptor divalent ion binding site(s) in this mechanism of ligand binding has been investigated. As compared with other divalent cations, Mn2+ ions have the unique property to dramatically stimulate the adhesive functions of the leukocyte integrin CD11b/CD18 (Mac-1), expressed on myelo monocytic cells. This is reflected in a three- to fivefold increased early monocyte adhesion (less than 20 min) to resting, unperturbed endothelial cells, and increased association of CD11b/CD18 with its soluble ligands fibrinogen and factor X. CD11b/CD18 ligand recognition in the presence of Mn2+ ions is specific, time and concentration dependent, and inhibited by anti-CD11b mAb. At variance with Ca(2+)-containing reactions where CD11b/CD18 functions as an inducible receptor activated by adenine nucleotides or chemoattractants, Mn2+ ions induce per se a constitutive maximal ligand binding capacity of CD11b/CD18, that is not further modulated by cell stimulation. Rather than quantitative changes in surface density, Mn2+ ions increase the affinity of CD11b/CD18 for its complementary ligands up to 10-fold, as judged by Scatchard plot analysis of receptor:ligand interaction under these conditions. Furthermore, monocyte exposure to Mn2+ ions induces the expression of activation-dependent neo antigenic epitopes on CD11b/CD18, selectively recognized by mAb 7E3. These data suggest that in addition to cell-activating stimuli, favorable engagement of divalent ion binding site(s) can provide an alternative pathway to rapidly regulate the receptor affinity of leukocyte integrins. PMID- 1890308 TI - Lipoproteins of Borrelia burgdorferi and Treponema pallidum activate cachectin/tumor necrosis factor synthesis. Analysis using a CAT reporter construct. AB - Lipoproteins from two pathogenic spirochetes (Borrelia burgdorferi and Treponema pallidum) induced the biosynthesis of TNF in murine macrophages and in permanently transformed macrophages of the cell line RAW 264.7. Induction was studied by measuring the secretion of biologically active TNF and by measuring the activity of the reporter enzyme chloramphenicol acetyltransferase (CAT) produced within macrophages transfected with an endotoxin-responsive CAT construct. Several lines of evidence indicated that the induction of TNF and CAT was attributable to the spirochete lipoproteins rather than to contaminating or endogenous LPS: 1) the dose response curves observed for the lipoproteins were markedly different from those obtained with LPS; 2) lipoprotein-mediated activation was unaffected by amounts of polymyxin B that completely neutralized the induction of TNF and CAT by LPS, 3) low concentrations of the lipoproteins induced TNF in macrophages from endotoxin-unresponsive C3H/HeJ mice as effectively as in macrophages from normal C3H/HeN mice, and 4) isolated spirochete lipoproteins, but not a non-lipoprotein immunogen, were potent inducers of CAT in the transformed macrophages. Moreover, LPS was not detected in the B. burgdorferi lipoprotein mixtures by Limulus amebocyte lysate assay. Proteolytic digestion of the intact bacterial protein preparations only modestly diminished their ability to activate the cells, suggesting that small lipopeptides comprise the biologically active portions of the molecules, as is the case with the murein lipoprotein of Escherichia coli. Through their ability to induce TNF production by macrophages, spirochete lipoproteins may play important roles in the development of the local inflammatory changes and the systemic manifestations that characterize syphilis and Lyme disease. PMID- 1890309 TI - Induction of the immune response to Legionella pneumophila cytolysin by monoclonal anti-idiotypic antibodies. AB - A panel of mAb (IgG1, IgG3, IgM) against Legionella pneumophila cytolysin (CL) protease of 37 kDa was obtained. Subtyping of L. pneumophila strains of serogroup 1 by using mAb against CL (mAb-CL) was carried out. The results of comparative analysis of the specificity of mAb-CL and the panel of mAb kindly provided by Dr. J. M. Barbaree (Centers for Disease Control, Atlanta, GA) allowed us to recommend mAb-CL to be used as a diagnostic tool to reveal the pathogenicity of L. pneumophila strains of serogroup 1. Hybridomas were also raised in a syngenic system which produced anti-idiotypic mAb (mAb2) against anti-CL mAb B6/1. The Ab2 belonged to Ab2 gamma type: 1) Ab2 reacted with B6/1 Id only, 2) Ab2 inhibited the interaction of B6/1 Ab1 with CL, and 3) CL inhibited the reaction of Ab2 with Ab1. The use of Ab2 allowed us to show that B6/1 Id is expressed in 4 to 32% of serum antibodies during the primary and secondary immune responses of BALB/c mice to CL. Ab2 induced the production of anti-anti-idiotypic antibodies (Ab3) in BALB/c mice, and some of them reacted with CL. Thus, we have demonstrated the possibility of inducing an antibody response to CL (one of the main L. pneumophila pathogenic factors) in intact syngenic mice with anti-idiotypic antibodies. PMID- 1890310 TI - Molecular characterization of a supratypic cross-reactive idiotype associated with IgM autoantibodies. AB - Neoplastic B cells from patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphomas (SLL) frequently express surface Ig reactive with the mouse mAb, Lc1. Raised against a human monoclonal IgM with rheumatoid factor activity, Lc1 detects a major cross-reactive Id (CRI) present on the H chain of many monoclonal IgM autoantibodies. In contrast to other major autoantibody-CRI investigated to date, we note that the Lc1-CRI is expressed by subpopulation of cells in the germinal centers, as well as in the mantle zones, of secondary human B cell follicles. To examine the molecular basis for Lc1 expression, we used the polymerase chain reaction to isolate the functionally rearranged Ig VH genes of monoclonal Lc1-reactive B cell populations from six unrelated patients with CLL or SLL. Although the neoplastic B cells from most patients with CLL or SLL express the CD5 surface differentiation Ag, the lymphoma cells from one patient with SLL were CD5-negative. We find that the Lc1-reactive cells from each cell population have Ig rearrangements involving a VH gene of the VH4 subgroup. However, the VH4 genes rearranged in different Lc1-reactive tumor populations may originate from at least two disparate germ-line VH4 genes. Also, in contrast to the CD5-positive tumor populations, we find evidence for intraclonal diversity in the functionally rearranged VH4 genes of the CD5-negative SLL. Collectively, this study discerns a degeneracy in the VH4 genes that can encode the Lc1 CRI, indicating the term "supratypic cross-reactive idiotype" may best describe the specificity of the Lc1 mAb. Also, this study suggests that expression of CD5 may delineate categories of B cell SLL that differ in their relative rates of constitutive Ig V gene somatic mutation. PMID- 1890311 TI - Analysis of anti-tumor antibodies in mice and rabbits induced by monoclonal anti idiotope antibodies. AB - Eight different mouse monoclonal anti-idiotope antibodies (mAb2) generated against a mouse monoclonal anti-human melanoma proteoglycan Ag (MPG) antibody (mAb1), MEM136, were tested for their ability to induce anti-MPG responses in mice and rabbits. All Ab2 were idiotypically cross-reactive and combining site specific as demonstrated by competitive cross-inhibition studies and their ability to inhibit the binding of MEM136 to the melanoma cells, Colo38. However, only two Ab2, IM32 and IM06, were able to induce specific anti-TAA-specific (Ab1') responses in rabbits. When IM32 and IM06 were tested in allogeneic stains of mice for the induction of anti-MPG responses, only IM32 produced an Ab1' response. In mice, the Ab3 response induced by IM32 is idiotypically cross reactive with its Ab1. Furthermore, the IM32-induced murine Ab3 and MEM136 recognized a similar MPG epitope on the melanoma cells because the Ab3 inhibited the binding of MEM136 to melanoma cells. The Ab3 induced by IM32 and IM06 in rabbits also recognized a similar epitope as the Ab1. In rabbits, the Ab3 response induced by IM32 and IM06 were idiotypically cross-reactive with each other. However, additional studies indicated that the majority of Ab3 induced by IM32 were IM32 Id-specific and lacked IM06 idiotopes. Further experimentation indicated that IM32-induced rabbit Ab3 were biologically active as demonstrated by the ability of the Ab3 to inhibit melanoma cell invasion in a Matrigel assay. PMID- 1890312 TI - Recognition of chromosome 6-associated target structures by human lymphokine activated killer cells. AB - Different populations of unstimulated and IL-2-activated PBL were used in binding and killing assays against somatic mouse/human lymphocyte cell hybrids containing different human chromosomes. Unstimulated PBL effector cells showed low binding and killing activity to both cell hybrids and mouse parental cell lines. However, IL-2-activated killer (LAK) cells bound strongly to, and effectively killed, cell hybrids carrying human chromosome 6, but were inefficient in both assays to mouse parental cells and to cell hybrids not carrying human chromosome 6. These results show that human LAK cells but not endogenous NK cells bind and kill mouse/human lymphocyte hybrids containing human chromosome 6. We thus suggest that LAK cells recognize ligands encoded by genes on chromosome 6. PMID- 1890313 TI - Relation between surgery-induced prolactin increase and the menstrual cycle phase at time of surgery in premenopausal breast cancer. AB - It has been suggested that both the menstrual cycle phase and postoperative changes in prolactin (PRL) secretion at the time of surgery may influence the prognosis of breast cancer. The present study was carried out to evaluate the relation between menstrual cycle period and surgery-induced PRL variations. We evaluated 32 premenopausal women with operable breast carcinoma; 17 were in perimenstrual phase (days 1-6 and 21-28) and 15 were in the mid-cycle (days 7-20) period at the time of surgery. To investigate serum levels of PRL, venous blood samples were collected before and 7 days after surgery. Postoperative hyperprolactinemia occurred in 17/32 patients and it was statistically more frequent in patients surgically treated during the perimenstrual phase than in the mid-cycle phase (12/17 vs 5/15; p less than 0.05), while no other parameter (including axillary node and estrogen receptor status) showed a significant influence on hyperprolactinemia rate. The results suggest that in premenopausal breast cancer patients surgery-induced hyperprolactinemia may be influenced by the menstrual cycle phase at the time of surgery. PMID- 1890314 TI - A role for tumor markers in therapeutic decisions after chemotherapy induction of objective remission in stage III epithelial ovarian neoplasms. AB - The management of advanced stage ovarian carcinomas is presently based on initial surgical debulking, multiple drug chemotherapy including cisplatinum, second-look laparotomy. Such an aggressive approach has improved objective response rates and expected survival time, but no dramatic change has been demonstrated as for definitive cure percentages. Many Authors have attempted to turn an optimal objective response to chemotherapy (no residual or minimal residual disease at second-look) into a definitive cure with irradiation. Some reports show satisfactory results, but a high incidence of bowel obstructive complications has been demonstrated, probably due to multiple surgical manipulations before radiotherapy. A reliable diagnostic tool, that could help to avoid the second look laparotomy (whose inherent role in improving survival is not assessed) should be therefore useful. The possible role of serum tumor markers determinations, for this purpose, is here discussed on the ground of a series of 20 patients affected by stage III ovarian carcinoma. Following this experience, a valuable role seems attributable to CA 125 in monitoring tumor response. Patients achieving values under 35 U/ml before second-look laparotomy showed tumor residuals in the range O-microscopic- less than 1 cm., that is, neoplastic localizations reliable for consolidation radiation therapy. PMID- 1890315 TI - Tumour associated antigens CA 15.3 and CA 125 in ovarian cancer. AB - CA 125 and CA 15.3 antigens were determined by enzyme immunoassay in 78 patients with ovarian cancer for a total of 540 determinations. The antigens were also investigated in sera from 100 women with other gynaecological diseases, 82 lung cancer patients and in 39 pleural fluids of varying origin. CA 15.3 reference values were evaluated in 91 healthy women (cut-off: 25 U/ml). CA 15.3 sensitivity at diagnosis (60%) and for detecting relapse (44%) was lower than that of CA 125 (90% and 64.7%, respectively). However, CA 15.3 does not increase with aspecific mesothelial cell reaction and thus it is more specific than CA 125. Combined use of the markers during follow-up improves early detection of relapse (at least one of the two was positive in 79% of cases). Therefore both CA 15.3 and CA 125 should be routinely determined for the detection and monitoring of ovarian cancer. PMID- 1890316 TI - Circulating immune complexes in human breast cyst fluids: relationship with intracystic immunoglobulin and electrolyte levels. AB - Circulating immune complexes, the major classes of immunoglobulins and electrolyte concentrations were measured in sixty-two breast cyst fluids aspirated in women affected by gross cystic breast disease. Two main classes of cysts were defined according to the Na/K ratio. Appreciable levels of immunoglobulins were found in almost all samples examined; 66% of breast cyst fluids showed increased levels of immune complexes. A highly significant linear correlation between increased values of immune complexes and immunoglobulin M (p less than 0.001) was found in apocrine cysts, characterized by Na/K ratio less than 3. However, a significant inverse linear correlation was found between positive values of immune complexes and lowered levels of immunoglobulins A (p less than 0.001) and G (p less than 0.001) in epithelial cysts with Na/K ratio greater than 3. These data suggest and confirm that the menstrual cycle can also influence or modulate the metabolic activity of human breast cells as a part of the secretory immune system. The relationship between immune complexes and immunoglobulins and electrolyte profiles may provide further knowledge about the immunological features of breast cyst fluid and suggest the possible alteration of immune-response in cystic breast lesions associated with increased cancer risk. PMID- 1890318 TI - A new procedure for gangliosidic N-acetylneuraminic acid analysis in serum. AB - In this paper a method is presented which is suitable for the extraction, purification and analysis of serum gangliosides. The advantage in comparison with other previously published procedures is the complete extraction of sialoglycolipids without contamination of sialoglycoproteins and/or sialoglycopeptides. The method could be used as a second-level test for the diagnosis and follow-up of cancer patients, and also could be potentially used for pharmaco-kinetic studies after ganglioside treatment. PMID- 1890317 TI - Clinical evaluation of a new two-site assay for CA125 antigen. AB - As appropriate surgery and chemotherapy can improve both quality of life and survival of patients with ovarian adenocarcinoma, there has been a pressing need for "serodiagnostic" assays to enable close patient monitoring. CA 125 antigen has previously been described as a useful tumor marker of ovarian cancer. This is the first clinical evaluation of a radioimmunoassay using two new monoclonal antibodies, B27.1 and B43.13, that react with separate sites on the glycoprotein marker CA 125. Using the new assay, the majority of patients with clinically or radiologically detectable disease had serum CA 125 antigen levels well above the upper limit seen with random apparently healthy donors, while only three patients who were believed free of disease had elevated levels. Disease progression was associated with increasing values of serum CA 125 antigen, while response to therapy was associated with a steady decline in serum CA 125 antigen levels. Seven patients had steadily rising serum CA 125 antigen levels after initially having normal levels. The mean lead time between rise above normal and clinical or radiological evidence of relapse was 5 months (range 2 to 12 months). The merits of further surgical intervention are illustrated by the serial values of two patients followed after chemotherapy. The assay appears to have value in monitoring response to therapy and in detecting disease relapse at a time when appropriate therapeutic intervention is still possible or likely to be beneficial. Furthermore, monitoring CA 125 antigen was shown to be of benefit in assessing response to chemotherapy in a few patients with metastatic adenocarcinoma of unknown primary, and may be useful in this group of patients in determining those likely to benefit from aggressive chemotherapy. PMID- 1890319 TI - Oral lichen planus. A review. AB - Lichen planus is a mucocutaneous disease of unknown etiology which, according to current knowledge, may represent a cell-mediated immunological response to induced antigenic changes in the skin and mucosa. Oral lichen planus (OLP) is a disease of adulthood and as one of the most prevalent diseases affecting the oral mucosa it has been the subject of intensive research during recent years. Ultrastructural and immunohistochemical studies particularly dealing with the subepithelial inflammatory cell infiltrate and its relations to epithelial pathology, the basal cell region and the intraepithelial antigen presenting Langerhans' cells, have contributed vastly to our knowledge of the pathogenesis of OLP. However, the treatment of OLP still remains largely symptomatic because many as yet unknown factors, active in the disease process, still remain to be elucidated. PMID- 1890320 TI - Oral manifestations of AIDS-associated non-Hodgkin's lymphomas. AB - While B-cell lymphomas are frequently found in AIDS patients, reports on oral manifestations are rare. Among a group of 465 HIV-infected patients 5 presented with primary oral manifestations of a malignant B-cell lymphoma. The primary site of manifestation was the maxilla in 3 cases and the mandible in 2 cases. Based on the histological and immunohistochemical examination the tumors were differentiated as Burkitt's lymphoma (n = 1), as anaplastic large cell (ALC) lymphoma of the B-cell type (n = 1), as high-grade non-Hodgkin's lymphoma not classifiable according to the Kiel classification (n = 1), as immunoblastic plasmoblastic lymphoma (n = 1), and as centroblastic lymphoma (n = 1). Serum samples were negative for HTLV-I antibodies in 5/5 cases. PMID- 1890322 TI - Explantation procedure in the F-type and Bonefit ITI implant system. AB - The explantation technique for the ITI F-type and Bonefit implant system is described. Although implant survival rates are high, the risk of failure must be considered. In some cases implants will have to be removed for reasons other than failure of the implant itself. PMID- 1890321 TI - Mucoepidermoid odontogenic cyst. AB - This unusual cystic lesion was previously described as a lesion that has features of both botryoid odontogenic cyst and mucoepidermoid tumor and later was named as glandular odontogenic cyst. An additional case is reported and its clinicopathologic features described. The name "mucoepidermoid odontogenic cyst" is proposed. PMID- 1890324 TI - Stereophotogrammetry of facial soft tissue. AB - Stereophotogrammetry was employed to measure the 3-dimensional location of points on the surface of the face in a chosen system of coordinates. A 3-dimensional model (image) was computer-generated on the basis of these data. By using specifically determined points the face was postoperatively superimposed upon the preoperative model. Standardized models using the same coordinate system served to objectify surgically induced changes in different graphic representations (sectional planes, contour lines, differences in contour lines, perspective models, differential vector imaging). PMID- 1890323 TI - Cephalometric analysis of permanently snoring patients with and without obstructive sleep apnea syndrome. AB - Habitual heavy snoring may be considered a preliminary stage of sleep apnea syndrome. This investigation deals with the craniofacial morphology of 51 heavily snoring patients, with and without obstructive sleep apnea, and with 28 healthy control patients. The apnea group showed a reduced posterior airway and a posterior rotation of the mandible. Reduction of the anterior-posterior diameter of the cranial base, maxilla and mandible and vertical reduction of the posterior facial height appeared to be common facial characteristics in both snoring and apnea patients. These findings indicate an anatomical disposition for snoring and apnea. PMID- 1890325 TI - Sucking efficiency of early orthopaedic plate and teats in infants with cleft lip and palate. AB - Intraoral negative pressure during bottle feeding with two kinds of teats (a regular Nuk and a cleft Nuk) was measured in 7 infants with cleft lip and palate, 8 infants with cleft palate, 2 infants with cleft lip, 4 infants with operated cleft lip and palate and 7 normal infants. Infants with cleft lip and palate or cleft palate were unable to generate negative pressure before cleft lip and palate closure. The presence or absence of an early orthopaedic plate did not make any difference. In infants with unoperated cleft lip and with operated cleft lip and palate, peak negative pressure during feeding differed little from that of normal infants. PMID- 1890326 TI - Magnetic resonance in lesions of the parotid gland. AB - In a prospective study the relevance of magnetic resonance (MR) for the diagnoses of tumors of the parotid gland has been evaluated. Due to the excellent soft tissue contrast and also the possibility of imaging in various planes and sections and to the high resolution achieved by surface coils, it was possible to visualize the lesions and the surrounding anatomy in great detail. MR combines the advantages of ultrasound and computed tomography and is indicated if a tumor cannot be defined sharply by using ultrasound or CT. PMID- 1890327 TI - Effect of experimental disc perforation in sheep temporomandibular joints. AB - The effect of surgical perforation of the disc on intra-articular morphology was examined using sheep. Eight sheep had bilateral perforations and 2 animals were used as controls. After 8 months the sheep were killed and the joints examined radiologically and histologically. Osteophytes were seen on all the condylar radiographs. Histologically, there were proliferative changes in both the condylar and temporal surfaces adjacent to the disc perforations. PMID- 1890328 TI - Ultrasonography as a diagnostic aid in temporomandibular joint dysfunction. A preliminary investigation. AB - Twenty-five patients presenting with temporomandibular joint dysfunction were examined by both ultrasonography and arthrotomography. Ultrasonography produced an image of the TMJ which was at right angles to the image produced by arthrotomography, since the ultrasound picture was in the coronal plane; with ultrasonography the meniscus became more visible during mouth opening. Anterior displacement of the meniscus was associated with deeper location of the condylar head within the glenoid fossa whilst a perforated meniscus produced a bilobed image. This study has provided a preliminary look at ultrasonography of the TMJ and has shown promise for further work. The present images are not ideal for clinical use but they show the possible potential for non-invasive diagnosis which might be provided by higher resolution ultrasound equipment than that used in this study. PMID- 1890329 TI - [Relationship between general thoracic and cardiovascular surgery in our Japanese Association for Thoracic Surgery]. PMID- 1890330 TI - Thoracic surgery in the AIDS patient. AB - AIDS is a syndrome caused by HIV. The virus is spread by homosexual or heterosexual transmission and by infected blood or certain body fluids. Respiratory infections are the commonest cause of death, and diagnosis may be difficult. The fiberoptic bronchoscope (FOB) plays an essential role in diagnosing respiratory infections in AIDS and is important in minimizing the need for open lung biopsies. Various problems require thoracic surgical consultation and treatment. We do not consider it ethical to deny these patients help. There can be no "double standard" in the care of patients in the hospital or in the operating room since any of our patients may have HIV without our knowledge. PMID- 1890331 TI - Present status and problem of heart transplantation in Japan. PMID- 1890332 TI - [Is postoperative mechanical ventilation necessary in esophageal surgery?]. PMID- 1890333 TI - [Surgical treatment of active infective endocarditis]. PMID- 1890335 TI - [Surgery of elderly patients]. PMID- 1890334 TI - [Combined resection of the heart, lung and esophagus]. PMID- 1890336 TI - [Late results of Stanford A type aortic dissection]. PMID- 1890337 TI - [Surgery of complex congenital heart defects]. PMID- 1890338 TI - [Mitral valvuloplasty]. PMID- 1890339 TI - [Coronary artery bypass with arterial graft]. PMID- 1890340 TI - [Surgical technique in atrioventricular septal defect]. PMID- 1890341 TI - [Surgical technique in aortic arch aneurysm]. PMID- 1890342 TI - [Reconstruction of the bronchus]. PMID- 1890343 TI - [Reconstruction of the trachea and carina]. PMID- 1890344 TI - [Surgical treatment of reflux esophagitis]. PMID- 1890345 TI - [New techniques for reconstruction after esophagectomy]. PMID- 1890346 TI - [Mechanism of cytokinesis in Tetrahymena]. PMID- 1890347 TI - [Purification of nicotinic acetylcholine receptors from brain and ganglion]. PMID- 1890348 TI - [Regulation of liver-specific gene expression]. PMID- 1890349 TI - [Urinary 11-dehydro thromboxane B2 during toxemic pregnancies]. AB - The increased TXA2 and decreased PGI2 seen in the toxemic pregnancies suggest the imbalance of arachidonic metabolism. Thromboxane (TX) B2 was thought to be a suitable parameter of TXA2 production in vivo. However, recently it has come to be recognized that a large amount of TXB2 is readily produced and decomposed to 11-dehydro TXB2 during blood sampling. In this study, a new RIA method was established, capable of measuring the urinary 11-dehydro TXB2 level. (1) The samples were measured with a 125I-labeled RIA kit for 11-dehydro TXB2 (Amersham, U.K.). In this assay system a highly specific antibody to 11-dehydro TXB2 was used. (2) The values for urinary 11-dehydro TXB2 measured by the RIA correlated closely with those measured by gas chromatography-mass spectrometry (r = 0.95). (3) The mean 11-dehydro TXB2 value in non pregnant was 2.62 +/- 1.71ng/mg Cr, The mean values in the first, second and third trimesters of pregnancy were 4.57 +/- 2.45ng/mg Cr, 5.75 +/- 2.81ng/mg Cr, 6.33 +/- 2.60ng/mg Cr, respectively. (4) The mean 11-dehydro TXB2 value in toxemic pregnancy was 4.13 +/- 1.86ng/mg Cr, which was significantly lower than that in normal pregnancies. (5) There was a significant negative correlation (p less than 0.0001) between the urinary 11 dehydro TXB2 concentration and the blood pressure. PMID- 1890350 TI - [Flow cytometric DNA analysis of uterine endometrial carcinoma]. AB - The DNA content in individual cells from 40 cases of histopathologically normal endometria, 15 of endometrial hyperplasia and 68 of endometrial adenocarcinoma was measured by flow cytometry. An aneuploid cell population was found in 50% of malignant endometria, but in the remaining endometrial carcinomas, the flow cytometrical findings showed no difference from those of benign tissue. Aneuploidy was more common (77.8%) in poorly differentiated tumors than in highly differentiated tumors (35.5%). Two and more aneuploid cell populations were found in 8 cases of 34. The DNA indices of aneuploid tumors were classified into 3 groups: hyperdiploidy, low hyperdiploidy (DNA index range: 1.04-1.2) and high hyperdiploidy (DNA index range: More than 1.2). The proportion of tumors with a high DNA index tended to increase as tumors became less differentiated. In normal endometria the fraction of cells with DNA content corresponding to the s-phase (s fraction) was 8 +/- 3% on average in the proliferative phase. In well differentiated diploid tumors the s-fraction was 12 +/- 6%, but in moderately and poorly differentiated tumors it was higher (16.0% and 19.0%). PMID- 1890351 TI - [Significance of umbilical plasma concentrations of catecholamines and their metabolites in patients with term vaginal deliveries]. AB - In an attempt to further clarify the physiological significance of Catecholamine (CA) s in the feto-placental unit, umbilical plasma concentrations of CAs and CA metabolites, 3-methoxy-4-hydroxy-phenylglycol (MHPG), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were measured in cases of full-term vaginal deliveries by HPLC-ECD. Results were as follows. 1. Norepinephrine (NE) and epinephrine (E) levels were significantly higher in arterial than in venous plasma, but no significant arterio-venous differences were found with dopamine (DA) concentrations. 2. High concentrations of MHPG, DOPAC and HVA were demonstrated in both arterial and venous plasma. 3. DOPAC and HVA levels were significantly higher in arterial than in venous plasma, but no significant arterio-venous differences were noted with MHPG. 4. A significant positive linear relations hip was demonstrated between arterial levels of NE and MHPG as well as DA and DOPAC, DA and HVA. 5. Arterial plasma MHPG levels were correlated significantly with arterial plasma pH and pO2. These results suggest that, in the feto-placental unit, NE, E and DA turnover is increased at term vaginal deliveries, and NE and E secretion sensitively responds to fetal respiratory and metabolic states. In addition, it is suggested that the mechanism which controls the DA turnover is different from that of NE and E. PMID- 1890352 TI - [Clinico-pathological study of cervical carcinoma with massive infiltration of eosinophils]. AB - Eight patients with cervical carcinoma with massive stromal infiltration of eosinophils were selected for a clinicopathological study among 474 patients with cervical carcinoma at stages Ib-IIIb who underwent radical hysterectomy between 1971 and 1989 at Kyoto University Hospital. The 8 patients ranged in age from 28 to 48 years and had menstrual cycles. The peripheral leucocyte count in 5 patients showed eosinophilia of the peripheral blood. Histologically, the cervical carcinoma was a locally advanced tumor with invasion of more than 2/3rds the depth of the cervical wall in 6 cases, and with parametrial involvement in 4 cases. Massive infiltration of eosinophils was observed not only around the cancer nests but also within the regional lymph nodes. Mast cells expressing immunoreactivity for histamine were scarce around the tumor. Consequently, the production of an eosinophil chemotactic factor by the tumor cells was strongly suggested. PAS and Alcian-blue staining as well as electron microscopy revealed that the tumor cells in most cases had the histological characteristics of both squamous carcinoma and adenocarcinoma. Collectively, these clinicopathological characteristics of cervical carcinoma with massive infiltration of eosinophils distinguish this tumor from conventional cervical carcinomas. PMID- 1890353 TI - [Endosalpingosis in the pelvic peritoneum and pelvic lymph nodes]. AB - The pelvic peritoneum with macroscopic findings characteristic of endometriosis was biopsied in 18 cases at conservative surgery for endometriosis and examined. Pelvic lymph nodes removed in 76 cases at radical surgery for uterine cervical, corpus cancer or ovarian cancer patients were examined. In 3 of the 18 cases, endosalpingiosis was encountered in the pelvic peritoneum. In 2 of these 3 cases combined lesions of endometriosis and endosalpingiosis were observed. On the other hand, in 4 of the 76 patients with gynecological malignancies, benign glandular inclusions were found in pelvic lymph nodes. In 3 of these 4 patients, there was endosalpingiosis, and another there was endometriosis. Endosalpingiosis is an interesting lesion offering some clues to the histogenesis of endometriosis, and important in the differential diagnosis of malignant tumors. PMID- 1890355 TI - [Establishment and characterization of endometrial clear cell carcinoma cell line (TMCC-2)]. AB - A new cell line, designated TMCC-2, has been established from operation material from a woman with endometrial clear cell carcinoma. TMCC-2 was successively subcultured 40 times in about 1 year. The monolayer culture cell showed a pavement-like arrangement of polygonal and short spindle-shaped cells, and had a tendency to pile-up without contact inhibition. Since PAS positive and Alcian Blue negative substance could be seen in the cytoplasm, the cells were found to produce glycogen. The population doubling time, the saturation density and plating efficiency of the 25th passage cells were 24 hours, 1.8 x 10(5) and 23%, respectively. The nuclear DNA histogram obtained by flow cytometry showed two peaks at 2.1C and 4.1C. Therefore, the DNA index was 1.05. A tumor maker assay of the culture medium revealed significantly high values for TPA, CA125, CA19-9, and SLX compared with the control medium. The TMCC-2 cells produced the tumors in nude mice after subcutaneous transplantation. In addition, the histological findings were similar to those in the original tumor. As mentioned above, the TMCC-2 cell line derived from endometrial clear cell carcinoma will be very valuable in basic research on clear cell carcinoma of the endometrium. PMID- 1890354 TI - [Significance of the detection of serum specific IgA and IgG antibodies to Chlamydia trachomatis in the epidemiological survey, diagnosis and therapeutic effect on chlamydial infection in women]. AB - In a study to evaluate the epidemiological status of Chlamydia trachomatis (C. trachomatis) infections in the OB/GYN field, we performed an indirect enzyme immune assay, measuring serum specific IgG and IgA. 1) Among 1,812 cases (0-68 years old), antibody positive rates for IgG and IgA were 29.7% and 11.2%, respectively. The first peak was observed in an age group under 1 year old, representing birth canal infections and the second one in a 20-24 age group showed a certain relation to STD. 2) The C. trachomatis IgG and IgA antibody positive rates in the antigen positive group (139 cases) were significantly higher (p less than 0.01) than in the antigen negative group (792 cases). 3) In the antigen positive group (139 cases), the positive IgG rate was high (78.8 90.9%) but it did not show any clear differences among the following groups: PID, cervicitis, pregnancy and infertility. However, the positive IgA rate in peritoneal antigen positive PID showed a significantly higher positive rate (100%) than other groups such as cervicitis (39.4%), pregnancy (37.8%) and infertility (45.5%). 4) Following oral administration of antibiotics, the C. trachomatis antigen became negative in almost all cases, while IgG decreased or became negative only in cases of initial infection. IgA decreased or became negative in the following cases: initial infection, low titer cases before treatment, cases treated many times and comparatively young patients with acute infections. Consequently, the immunoassay of C. trachomatis serum antibody appeared to be valuable for epidemiological surveys, for defermining the status of the infection and the effect of treatment. PMID- 1890356 TI - Effects of longitudinal maternal glucose control on infants of diabetic mothers. AB - Between 1980 and 1987, 45 pregnant women with diabetes mellitus who required insulin therapy were delivered at Kagoshima Municipal Hospital. The perinatal mortality rate in the present study was zero. Twelve infants were large for gestational age, ten were small for gestational age, and 23 were appropriate for gestational age. Tight maternal glucose control (fasting values of less than 100mg/dl and 2 hours post-prandial values of less than 120mg/dl) obtained before 32 weeks of gestation significantly decreased the incidence of large for gestational age infants. However, longitudinal control patterns of maternal glucose during pregnancy have little effect on the incidence of small for gestational age infants and neonatal complications. The former was more closely related to maternal vascular complications. Congenital malformations were found in two cases. PMID- 1890357 TI - The effect of an acute stress in late pregnancy on hypothalamic catecholamines of the rat fetus. AB - Prenatal stress in the last trimester of pregnancy induces permanent disorders in sex-specific differentiation of the brain in rats. In order to determine the neuroendocrine response of the fetal hypothalamus to the maternal stress, we investigated the temporal change in fetal hypothalamic catecholamines when their mothers were exposed to an acute stress. On day 20 of gestation, pregnant rats were subjected to forced immobilization and sacrificed at 0, 30, 60, 120 and 180 minutes. Plasma corticosterone reached a peak at 60 minutes of stress in mothers and fetuses. Hypothalamic norepinephrine and epinephrine decreased at 120 and 180 minutes of stress in mothers, whereas in fetuses, hypothalamic norepinephrine decreased at 120 and 180 minutes of stress, and dopamine also showed a tendency to decrease. These results suggest that maternal stress in late pregnancy decreases fetal hypothalamic norepinephrine which is involved in androgen dependent sex differentiation of the brain. PMID- 1890358 TI - [Human chorionic gonadotropin levels in the follicular fluid in relation to oocyte maturity in in vitro fertilization]. PMID- 1890359 TI - [Nucleolar organizer region in human endometrial cells]. PMID- 1890360 TI - [Marshall-Marchetti-Krantz operation for urinary stress incontinence]. PMID- 1890361 TI - A clinical, immunological, and histological study of neuritic leprosy patients. AB - An assessment has been made of 108 neuritic leprosy patients to find out if the number of affected nerves and the clinical presentations of these patients give any indication of the underlying severity (classification) of the disease. Detailed clinical recordings, skin smears, lepromin testing with Dharmendra antigen, and a leukocyte migration inhibition test (LMIT) using sonicated Mycobacterium leprae antigens were done in these patients. Nerve biopsies of available affected nerves were taken in 39 patients. The results show that neuritic leprosy patients also have a spectrum. However, none of the clinical parameters, including the number and distribution of affected nerves, the immune response and the nerve histology, were found to be inter-related. Further, even though all of the patients were skin-smear negative, a significant proportion showed lepromatous histology and nearly two thirds had a moderate-to-heavy bacterial load within the nerves. PMID- 1890362 TI - Progression of eye lesions in leprosy: ten-year follow-up study in The Netherlands. AB - Forty-eight leprosy patients in The Netherlands were re-examined 10 years after initial examination. Forty-six of these patients had received a course of multidrug therapy (MDT), according to the World Health Organization recommendation, at the time of their initial examination. Two patients had burned out disease and had been merely under observation. Out of 40 patients, who initially did not show eye complications due to leprosy, 37 patients were essentially the same 10 years later. The eyes had changed in 3 multibacillary patients: 1 patient had developed a late type 1 reaction with facial nerve involvement and lagophthalmos; 2 patients had undergone intra-ocular surgery for cataract and acute glaucoma, respectively. Out of 8 patients with pre-existing eye involvement, 1 patient recovered and the lesions in 2 patients remained unaltered. One patient showed progression of pre-existing exposure keratitis. Four patients had undergone cataract extractions; all four patients were lepromatous, with a long history of disease and signs of iris involvement at the first examination. The main progressive lesions were cataracts in lepromatous patients. PMID- 1890363 TI - Detection of M. leprae-specific antigens with dot-ELISA in urine and nasal samples from leprosy patients. AB - One-hundred-two urine and nasal samples collected from leprosy patients of different classifications of disease were studied for the presence of Mycobacterium leprae antigens, including phenolic glycolipid-I (PGL-I). Lipids were extracted from the urine samples, and nasal washings were concentrated and used as such in the dot-ELISA. Two types of primary antibodies, a polyclonal antibody obtained from lepromatous (LL) leprosy patients' pooled and absorbed sera and an anti-PGL-I monoclonal antibody, were used for the detection of M. leprae antigens from these samples. The polyclonal sera detected 23% to 36% of the paucibacillary (PB) and 100% of the multibacillary (MB) leprosy cases from the urine samples. Corresponding values for nasal detection were 10% to 18% for PB and 100% for MB cases. The monoclonal antibody against PGL-I could not detect tuberculoid (TT) leprosy cases. From the urine samples, however, 16% of the borderline tuberculoid (BT), 25% of the borderline (BB), 80% of the borderline lepromatous (BL), and 100% of the LL leprosy cases were detectable. It was interesting to note that PB, skin-smear negative cases were detectable from urine examination. The specificity and sensitivity of the test is discussed in relation to the crossreacting antigens. PMID- 1890364 TI - IgM antibodies to native phenolic glycolipid-I in contacts of leprosy patients in Venezuela: epidemiological observations and a prospective study of the risk of leprosy. AB - In a randomized, double-blind vaccine trial in Venezuela, about 29,000 contacts of leprosy patients have been vaccinated with either a mixture of heat-killed Mycobacterium leprae and BCG or BCG alone, and are being re-surveyed annually to detect new cases of leprosy. All contacts had a serum sample collected at the time of entry into the trial, and 13,020 of these sera have been analyzed for antibodies to phenolic glycolipid-I (PGL-I). Antibody levels have been related to various characteristics of the contacts and to their risk of developing leprosy in the following 4 years. A strong association was found between PGL-I antibody level and the risk of developing leprosy, in spite of possible modification of the incidence rate induced by vaccination. Antibody levels were higher in females than in males, and declined progressively with age. Household contacts had higher levels than did non-household contacts, and levels were higher in individuals from the state in Venezuela which has the highest incidence of the disease. No substantial differences were found in antibody levels between contacts of multibacillary and paucibacillary patients, which may in part reflect the influence of treatment, and there was no clear association with the presence of BCG or lepromin scars or with skin-test responses to PPD and leprosy soluble antigen. The assay of antibodies to PGL-I seems unlikely to provide a sensitive or specific test for infection with M. leprae, and measuring PGL-I antibody levels as a screening procedure to identify those at high risk of developing leprosy is unlikely to be particularly useful in most leprosy control programs. Such assays may be useful for the epidemiological monitoring of changes in the intensity of infection with M. leprae in a community and for the study of carefully defined groups of contacts during some phases of control programs. PMID- 1890365 TI - A seroepidemiological study of leprosy in high- and low-endemic Indonesian villages. AB - A seroepidemiological study was performed in three different leprosy-endemic areas in Indonesia, including two isolated villages with high endemicity in South Sulawesi (Kaluarang and Hulo) and an area with low endemicity in Java (Jepara). A total of 2430 serum samples were collected from 2672 individuals in these locations. The prevalence of leprosy in these three areas, as determined during this study, was 29/1000, 11/1000, and 7/1000 in Kaluarang, Hulo and Jepara, respectively. Two serological assays were employed in this study to detect antibodies against Mycobacterium leprae. One is an enzyme-linked immunosorbent assay (ELISA) based on the detection of antibodies to the species-specific epitope of phenolic glycolipid-I (PGL-I) of M. leprae. The second test, using inhibition of an ELISA reaction (ELISA-INH) detects antibodies to a species specific epitope on the 36-kDa protein antigen of M. leprae. In comparison with clinical findings, the specificity of both serological tests was calculated to be 91%. The sensitivity of the ELISA was 97.6% for multibacillary (MB) cases and 56.8% for paucibacillary (PB) cases; for the ELISA-INH, it was 97.6% and 81.8% for MB and PB cases, respectively. Seropositivity rates were shown to be unrelated to sex, to Mitsuda skin-test reactivity, or to BCG vaccination status. The pattern of seropositivity was, however, clearly age-related, with high seropositivity in the age group 10-19 years and decreasing rates of positivity in the older age groups. Age-standardized seropositivity ratios were not correlated to the prevalence of leprosy when comparing the three areas. Therefore, it is not yet clear whether or not seropositivity reflects infection. If it does, other, as yet unidentified, factors may play a role in the natural history of the disease. PMID- 1890366 TI - Seroepidemiological study of leprosy in a highly endemic population of south India based on an ELISA using synthetic PGL-I. AB - As part of a continuing longitudinal immuno-epidemiological study, blood samples were collected by finger prick from 4243 individuals living in a highly endemic area for leprosy in South India. The samples were tested for IgM antibodies against phenolic glycolipid-I using an ELISA. Seropositivity defined as optical density greater than or equal to 0.2000 was marginally higher in the age group 10 30 years and in females. There was no evidence for a higher level in contacts than in non-contacts. The future prospect for the large scale use of this ELISA in high-endemic populations in special epidemiological investigations or routine control programs as a serological tool to detect leprosy infection appears questionable. PMID- 1890368 TI - Serum IgA1 and IgM antibodies against Mycobacterium leprae-derived phenolic glycolipid-I: a comparative study in leprosy patients and their contacts. AB - In order to evaluate the potentials of IgA1 versus IgM as well as of native phenolic glycolipid-I (PGL-I) versus PGL-I-disaccharide coupled to bovine serum albumin (D-BSA) as antigens in the serodiagnosis of leprosy, anti-D-BSA IgA1 and anti-PGL-I IgM were investigated and compared to anti-PGL-I IgA1 in sera from patients and contacts. Anti-D-BSA and anti-PGL-I IgA1 significantly correlate in patients and contacts. The higher IgA1 positivity rates obtained with D-BSA as compared to PGL-I may suggest D-BSA as the favorable antigenic material. In patients but not in contacts anti-PGL-I IgM and IgA1 correlate, IgM predominating over IgA1. In all three antibody systems, the mean values as well as the positivity rates increased from the tuberculoid toward the lepromatous disease pole. Also, the levels of all three antibodies significantly increased with the bacterial index (BI). However, anti-D-BSA (PGL-I) IgA1 appears to be preferable to IgM with respect to sensitivity, i.e., detection of disease activity, in paucibacillary or BI-negative patients. A number of contacts were detected as seropositive with anti-D-BSA and/or anti-PGL-I IgA1 but not with anti-PGL-I IgM. This suggests that IgA1 is a better tool than IgM for the detection of leprosy in its subclinical stage. PMID- 1890367 TI - The value of IgM antibodies to PGL-I in the diagnosis of leprosy. AB - An ELISA has been used to measure IgM antibodies to phenolic glycolipid-I (PGL-I) in previously undiagnosed patients who were suspected of leprosy on purely clinical grounds. The certainty of clinical diagnosis was classified as either "firm" or "indefinite." Leprosy was confirmed in 133 of 161 patients on the basis of positive slit-skin smears and/or skin and/or nerve histopathology. All 58 patients with multibacillary leprosy (BB, BL, or LL) were correctly diagnosed clinically, as were 50 of 54 patients (93%) with a firm diagnosis of BT or TT leprosy. The firm clinical diagnoses were more accurate than either the slit-skin smear or ELISA data. However, there were 44 patients (27% of total), designated "rule out leprosy" (RO), for whom the clinical diagnosis was indefinite. The clinical suspicion of leprosy (RO) was correct in only 24 (55%) of these patients who had BT leprosy. The slit-skin smears were positive in only 20% of these patients compared to 50% for the ELISA. It was concluded that the PGL-I IgM ELISA may have its greatest diagnostic confirmatory value in paucibacillary disease because paucibacillary leprosy comprises the major source of clinical diagnostic difficulty. PMID- 1890370 TI - Impact of multidrug therapy on the treatment and control of leprosy. PMID- 1890369 TI - A serologic study of naturally acquired leprosy in chimpanzees. AB - Data from longitudinally obtained serum samples spanning several years has permitted us to identify two chimpanzees with leprosy and to estimate the time of Mycobacterium leprae exposure/infection. The results confirm high levels of specific anti-M. leprae phenolic glycolipid-I (PGL-I) as well as anti-lipo arabinomannan (anti-LAM) antibodies in both chimpanzees, and identify additional chimpanzees with possible M. leprae exposure. The observations are consistent with the hypothesis that leprosy exists in chimpanzees in the U.S.A. and suggest the possibility that M. leprae may be transmitted among chimpanzees. The data suggest that monitoring anti-PGL-I and anti-LAM IgG and IgM levels longitudinally in leprosy contacts may be useful in the recognition of preclinical leprosy. PMID- 1890371 TI - Trigeminal trophic syndrome in Hansen's disease. PMID- 1890372 TI - Response to phytohemagglutinin of LL patients' lymphocytes preincubated in culture media. PMID- 1890373 TI - Mycobacterial cell surface proteins revealed by labeling with 125I. PMID- 1890374 TI - In vitro effect of dapsone on NADH-methemoglobin reductase. PMID- 1890375 TI - Effect of circulating immune complexes of leprosy patients on leukocyte migration inhibition induced by Mycobacterium leprae antigens in healthy volunteers. PMID- 1890377 TI - [Proceedings of the 6th meeting for orthopaedic research of the Japanese Orthopaedic Association. August 29, 30, 1991, Kyoto City]. PMID- 1890378 TI - Society for Leukocyte Biology. Membership directory. PMID- 1890376 TI - Hypothesis: solar ultraviolet radiation and the initial skin lesion of leprosy. PMID- 1890379 TI - Georgia's new "no code" law. PMID- 1890380 TI - Allocation of study time and recall by learning disabled and nondisabled children of different ages. AB - Study time and recall by learning-disabled and nondisabled children of five different ages were examined in a task requiring recall of digits that were presented at the child's own rate. Recall increased with age and was significantly higher by nondisabled than disabled children, particularly at older ages. As additional digits of each sequence were presented, study time by 8-year old disabled and nondisabled groups were relatively constant, increased in older disabled and nondisabled children, but increased more in older nondisabled children than older learning disabled children. Instructions in hierarchical grouping of digits increased recall by all groups to a similar degree, but the increase by younger children and learning disabled children was associated with longer study times. The results suggest that allocation of study time and recall are developmentally delayed in learning disabled children. PMID- 1890381 TI - Does object modeling elicit imitative-like gestures from young infants? AB - One interpretation of the evidence for early imitative-like matching of facial gestures is that the acts are elicited by stimulus properties, rather than constructed by the infant. Verification of this possibility requires presentation of object models to determine whether infants reliably respond to them with movement-matching gestures. Two object models, one simulating tongue movements and the other mouth opening/closing, were presented to younger infants (median age = 5 weeks) and to older ones (median age = 12 weeks) under systematically varied movement conditions. Additionally, a live model presented tongue protrusion and mouth opening gestures to the same infants. Findings of two studies were similar. At neither age was there reliable elicitation of facial gestures by either object model, which suggests that most infants were not imitating the object movements or responding to them in a way that verifies elicitation of facial matches by object presentation. Live modeling of tongue extensions, however, did increase the incidence of partial tongue protrusions among infants at 5 weeks, which supports previous research. PMID- 1890382 TI - Discounting in preschoolers: effect of type of reward agent. AB - The effect of type of reward agent on children's discounting was examined. In Study 1, 49 preschool children were told two stories illustrated with small dolls and toys. Subjects discounted intrinsic interest in toy A when a "big, mean brother" told a sibling that if he played with toy A he could play with toy B. Discounting did not appear when the reward agent in the story was the child's mother, which is the typical outcome in previous research with young children. Studies 2 and 3 suggested that the combination of a negative valence and a particular social role/status accounted for the effect of the big, mean brother of Study 1. More specifically, neither a "big brother" nor a "mean mother" as reward agents elicited a significant amount of discounting. The results suggest that social knowledge guides the application of the discounting schema. PMID- 1890383 TI - Transfer of control in ambiguous discriminations. AB - Rats' acquisition and transfer of performance in ambiguous discriminations was examined using discrete-trial operant lever-press procedures. Rats learned serial ambiguous discriminations (X----A+, A-; B+, X----B-) by acquiring both positive and negative occasion setting functions to the X feature. Mutual transfer occurred among cues from serial ambiguous, feature positive (Y----C+, C-), and feature negative (Y----C-, C+) discriminations, but that transfer did not extend to cues not trained within one of those serial discriminations. The ambiguous feature's positive occasion setting powers were unaffected by nonreinforced presentation of that feature alone, and posttraining counterconditioning did not eliminate the feature's ability to serve as a negative occasion setter. Occasion setting was not acquired with simultaneous ambiguous discriminations (XA+, A-; XB , B+), which apparently were solved with a configural strategy. PMID- 1890384 TI - Differential effectiveness of various prior-cuing treatments in the reactivation and maintenance of memory. AB - In 3 experiments, changes were examined in the characteristics of newly acquired and reinstated memories over time in preweanling rats. Experiment 1 indicated that forgetting after conditioning was monotonic, with the upper limit of retention at approximately 120 min posttraining. In Experiment 2, Ss were exposed to various elements of the training episode before testing, after either a 3- or a 24-hr retention interval. The results indicated that the prior-cuing treatments were differentially effective and that the effectiveness of a reactivation treatment may change as a function of the retention interval. Experiment 3 indicated that Ss expressed a conditioned aversion at much longer intervals following reactivation treatments than after initial conditioning. Furthermore the susceptibility of the reinstated memory to forgetting was dependent on the prior-cuing treatment used. The results suggest a change in the memorial representation of the conditioning episode over time. PMID- 1890385 TI - Reconsideration of the role of competing responses in demonstrations of the interference effect (learned helplessness). AB - In Experiment 1a, rats trained to escape shock by performing a 2-s inactive response were less impaired on a subsequent 2-way shuttle response than their yoked counterparts that received inescapable shock. In contrast, in Experiment 1b, rats trained to escape shock by performing a longer duration inactive response were more impaired on the subsequent escape task than their inescapably shocked counterparts. In Experiment 2, the results of Experiments 1a and 1b were replicated, and the inactive responses performed during pretreatment by both the escapable and inescapable shock groups were assessed and correlated with test stage 2-way shuttle escape performance. These activity data indicate that inactivity during pretreatment shock in both escapable and inescapable shock groups was a highly reliable predictor of subsequent 2-way shuttle performance, irrespective of the pretreatment shock contingency to which these Ss were exposed. PMID- 1890386 TI - Dynamics of time discrimination. AB - Pigeons tracked sinusoidal sequences of interfood intervals (IFIs) by pausing in each interval for a time proportional to the preceding interval. Schedules with either long (30-90 s) or short (5-15 s) values, with variable numbers of cycles and starting phase each day, were tracked about equally well. Tracking was apparently immediate and did not improve across sessions. Experiment 2, in which long and short series were presented on alternate days, showed that tracking on long was more impaired than on short. Experiment 3 showed that occasional presentation of a short IFI in a series of fixed, longer IFIs caused a reduction in waiting time in the next IFI. These effects are evidence for a fast-acting timing mechanism in which waiting time in the IFI N + 1 is strongly determined by the preceding IFI, N. Earlier IFIs have some cumulative effect, but the details remain to be elucidated. PMID- 1890387 TI - Selective attention and search images in pigeons. AB - In a visual search task, pigeons detected targets when pretrial visual cues or blocked trial sequences signaled the target's identity. Sequential priming was robust over a wide range of intertrial intervals, but visual priming was unstable when the delay between cue offset and display onset was varied. Larger target set sizes enhanced sequential, but not visual, priming. Sequential priming did not depend on display size over the range of relatively large displays used. However, ambiguously cued targets in small displays were detected more quickly than primed targets in large displays. These findings suggest that naturalistic selection biases, or "search images," may be attributable to sequential priming and that the common attentional mechanism has moderately selective properties. PMID- 1890388 TI - Modulation of a discrete Pavlovian conditioned reflex by a putative emotive Pavlovian conditioned stimulus. AB - Three experiments showed the modulation of a rabbit eyeblink conditioned response (CR) to a Pavlovian conditioned stimulus (CS) by 30-s stimuli (A & B) that had been differentially paired with paraorbital shock. The CS (Y) was a 1,050-ms cue that had been paired with paraorbital shock outside A or B. In testing, the amplitude of CRs was greater when Y was presented within A than within B. Differential modulation occurred whether shock in A had been preceded by another 1,050-ms cue, X(AX+,BX-;Experiment 1) or not (A+B-;Experiment 2). Experiment 3 compared the technique of Experiment 1 (AX+) with that of Experiment 2 (A+) and found the latter to be advantageous for facilitation of CRs to Y by A. These data are consistent with the predictions of a model of Pavlovian conditioning (AESOP, Wagner & Brandon, 1989) that distinguishes between emotive and sensory conditioning as did Konorski (1967). PMID- 1890389 TI - Modulation of unconditioned defense reflexes by a putative emotive Pavlovian conditioned stimulus. AB - Four experiments showed differential modulation of defensive unconditioned responses (URs) in rabbits by contextual stimuli that Brandon and Wagner (1991) have shown similarly to modulate conditioned eyeblink responses. Two 30-s auditory cues, A and B, were differentially paired with shock. Tests were presentations of a response-eliciting probe stimulus within A, B, or a comparable blank interval, Experiments 1 and 2 demonstrated that A and B differentially facilitated eyeblink URs, and Experiments 3 and 4 showed that A and B similarly differentially facilitated startle responses elicited by airpuffs to the ear. These data are consistent with a characterization of Pavlovian conditioning that distinguishes between emotive and sensory conditioning and assumes that conditioned emotional responses similarly modulate specific conditioned and unconditioned defensive reflexes (Konorski, 1967; Wagner & Brandon, 1989). PMID- 1890390 TI - Modulation of a conditioned eyeblink response by a putative emotive stimulus conditioned with hindleg shock. AB - Two experiments with rabbits showed that the differential modulation of a conditioned eyeblink response (CR) by 30-s auditory stimuli previously paired with shock was independent of the locus of shock application. In Experiment 1, the modulation occurred when the CR was trained with paraorbital shock and the 30 s stimuli were trained with either hindleg or paraorbital shock. Experiment 2 replicated the observed adequacy of hindleg shock for modulation training, under 2 different conditions of eyeblink conditioning. The data, along with the findings that the same 30-s stimuli similarly facilitate the unconditioned eyeblink and the airpuff-elicited startle response (Brandon, Bombace, Falls & Wagner, 1991), were viewed as supporting the notion that the CR-modulation is dependent upon a conditioned fear response elicited by the 30-s cues (Wagner & Brandon, 1989). PMID- 1890391 TI - Learning to discriminate the sex of conspecifics in male Japanese quail (Coturnix coturnix japonica): tests of "biological constraints". AB - Male Japanese quail learn to approach and remain near female, but not male, quail if they are allowed to copulate with female quail and receive noncopulatory exposures to males. The generality of the mechanisms involved in this type of discrimination learning was investigated in the present study. In Experiment 1, Ss learned to spend more time near initially unfamiliar blonde quail than familiar brown female or male quail as a result of being allowed to copulate with the blonde, but not the brown, quail. In Experiment 2, Ss learned to respond more to nonreproductive male as compared with female quail as a result of being allowed to copulate with the males, but not with the females. The experiments provided some evidence of a bias favoring responding to females independent of copulatory reinforcement contingencies. However, the results also indicated remarkable plasticity of discrimination learning about species-specific sexual stimuli. PMID- 1890392 TI - Perirectal abscess. PMID- 1890393 TI - MEDLINE. PMID- 1890394 TI - Clinical guidelines development: opportunities for family physicians. PMID- 1890395 TI - Networks and net worth: practice-based data collection in family medicine. PMID- 1890396 TI - Screening healthy people for diabetes: is it worthwhile? AB - BACKGROUND: The objectives of this study were (1) to estimate the prevalence of previously unknown diabetes mellitus in an apparently healthy population aged 40 years and older, (2) to estimate the ratio of known to unknown diabetics, and (3) from this information, to estimate the true prevalence of diabetes. METHODS: A one in five random sample of healthy patients aged 40 years and older attending six rural family physician offices had their fasting plasma glucose (FPG) level tested with a reflectance glucometer. If the FPG was greater than or equal to 7.8 mmol/L (140.5 mg/dL), a second FPG test was done on a later day. RESULTS: The sample of 1264 patients contained 139 known patients with diabetes. Of the remaining 1125 patients, 936 (83%) were tested. Twenty-three patients had an elevated FPG level on the first test, but only nine of them had an elevated FPG level on the second test. One new patient with diabetes was found for each 15 patients already diagnosed; thus, the prevalence of unknown diabetes in the study population was 0.7%. As a result of this survey, the estimated prevalence of diabetes in the population age 40 years and older rose from 11.0% to 11.7%, and the estimated prevalence for the entire population rose from 4.4% to 4.6%. CONCLUSIONS: Routine screening for diabetes mellitus in otherwise healthy patients aged 40 years and older is not worthwhile. Such screening should be restricted to high-risk groups. PMID- 1890397 TI - Koilocytotic atypia and underlying dysplasia. AB - BACKGROUND: Several studies have examined the agreement between Papanicolaou smear cytology and subsequent biopsy results in the diagnosis of cervical dysplasia. However, few studies have focused specifically on koilocytotic (KC) atypia. Given the increasing frequency of reporting KC atypia on Papanicolaou smears, we sought to obtain more information on the relationship between Papanicolaou smears and subsequent colposcopically directed cervical biopsies. METHODS: Retrospectively, we compared the Papanicolaou smears and colposcopically guided biopsy results for 132 college women who had abnormal Papanicolaou smears (KC, cervical intraepithelial neoplasia [CIN], or reactive atypia [RA]). Data were compiled through systematic review of the charts of these women. The cervical biopsies were taken 6 months or less after the Papanicolaou smears. RESULTS: Of 99 women having only KC atypia on cytology, histology revealed concordance in 51 cases and underlying dysplasia in 16 cases. Only one biopsy revealed CIN III, and no biopsies showed invasive carcinoma. We also noted variation in the histologic results between the laboratories that analyzed the biopsy specimens. In comparing the biopsy results after one or two KC atypic Papanicolaou smears 6 months or less apart, we found no statistically significant difference. CONCLUSIONS: These findings suggest that physicians who obtain an initial Papanicolaou smear read as KC atypia could obtain a second smear 3 months later to determine if there is persistent KC atypia before advising a patient to have cervical biopsy. In addition, physicians also should know the limitations of the laboratories providing them with information. PMID- 1890398 TI - Student athlete cholesterol screening during routine precompetition examination. AB - BACKGROUND: When properly organized and conducted, the preseason physical examination process for scholastic athletes can identify existing medical and musculoskeletal problems as well as provide for age-specific anticipatory guidance. This examination may also present an ideal opportunity to screen for adolescent hyperlipidemia. METHODS: Seven-hundred seventy-seven (777) students, aged 11 to 15 years, from seven junior high schools received fingerstick cholesterol screening during a complete preseason physical examination. Elevated values were verified by repeat examination. Values were compared with previously published national norms for this age group. All students received information on cholesterol, and the parents and pediatrician or family physician of those with confirmed positive tests (higher than 4.8 mmol/L [185 mg/dL]) were notified. RESULTS: One hundred fourteen (114), or approximately 15%, of the subjects were found to have elevated cholesterol levels. Of the 74 who returned for a second test, 38 (51%) were confirmed as having elevated cholesterol levels. Feedback from parents, principals, and coaches regarding the value of the screening and the associated education was overwhelmingly positive. CONCLUSIONS: In our experience, the precompetition examination provides an opportunity to screen for elevated cholesterol levels and to educate young people about hyperlipidemia. PMID- 1890399 TI - Psychiatric side effects associated with the ten most commonly dispensed prescription drugs: a review. PMID- 1890400 TI - Effect of repeated annual reminder letters on influenza immunization among elderly patients. PMID- 1890401 TI - Late tubo-ovarian abscess following abdominal hysterectomy. PMID- 1890402 TI - Papillophlebitis, optic disc vasculitis. PMID- 1890403 TI - Expression of epidermal growth factor (EGF) and the EGF receptor in human tissues. AB - The EGF-EGF receptor system has been widely examined for signal transduction, control of cell growth and differentiation, and in vivo physiological function and carcinogenesis. The localization of EGF receptors in vivo led to the idea that the system is operative in proliferation and differentiation of cells and tissues. However, a consensus for its distribution and function in human tissues has not yet been determined because of discrepancies in the reported results. Using a highly specific monoclonal antibody against the EGF receptor, we examined various tissues of an infant and adults as well as embryonal carcinoma. We observed restricted localization of EGF receptors in basal cells of epithelial tissues and duct cells of secretory tissues. Fibroblasts express a high level of EGF receptors when they are rapidly growing. Using the monoclonal anti-EGF antibodies, we observed that EGF is localized to differentiated cells rather than to stem cells such as glandular tissues. We also observed that some cells express both EGF and the EGF receptor. All histochemical results indicated that in epidermis and various glandular tissues, EGF may be expressed in differentiating cells derived from the stem cells expressing EGF receptors. PMID- 1890404 TI - Expression of an antigen specific for trunk lateral cells in quarter embryos of the ascidian, Halocynthia roretzi. AB - Cell-lineage analysis has demonstrated that a pair of the right and left A7.6 cells of a 64-cell embryo of the ascidian Halocynthia roretzi, descendants of A4.1 cells of an 8-cell embryo, give rise to trunk lateral cells (TLCs). In this study, in order to investigate cellular mechanisms involved in the specification of TLCs, we have examined the expression of a TLC-specific antigen in cleavage arrested embryos and in quarter partial embryos. Although cleavage arrest of embryos by treatment with cytochalasin B at early stages, prior to and including the 16-cell stage, inhibited expression of the TLC-specific antigen, embryos arrested at the 32-cell stage and at later stages developed the antigen. The only blastomeres exhibiting expression of the antigen were the presumptive TLCs, as predicted by cell-lineage assignments. When the developmental potential of quarter embryos that originated from four isolated blastomere-pairs (a4.2, b4.2, A4.1, and B4.1 pairs) of an 8-cell embryo was examined, the A4.1 quarter embryos, which are developmentally fated to give rise to TLCs, rarely showed evidence of expression of the antigen. Expression of the antigen was not observed in a4.2 and b4.2 quarter embryos, which are not associated with the TLC fate. By contrast, expression of the antigen was detected in about a half of the B4.1 quarter embryos which are also not associated with the TLC fate. These results are discussed with reference to the relationship between TLCs and mesenchyme cells. PMID- 1890405 TI - Developmental interactions in the pigmentary system of the tip of the mouse tail: effects of coat-color genes on the expression of a tail-spotting gene. AB - The tails of agouti C3H/HeJmsHir mice are completely pigmented, whereas the tails of black C57BL/10JHir animals possess unpigmented tips. Genetic analysis indicates that white tail-tipping is due to an autosomal recessive gene, with incomplete penetrance, that segregates independently from the gene for agouti with a maternal influence in the F1 generation. To analyze the influence of specific coat-color genes on the expression of tail-spotting in mice, five congenic lines of C57BL/10JHir with different coat colors were prepared. No influence was observed on the occurrence of tail-spotting in agouti (A/A) or dilute (d/d) mice or in F1 mice from crosses between black and albino (c/c), or in F1 mice from crosses between black and pink-eyed dilution (p/p). However, the frequency of tail-spotting was dramatically decreased in brown (b/b) mice. These results suggest that the mutant allele (b) at the brown locus is involved in determining the extent of pigmented areas in the tail tips of mice through an interaction with the tail-spotting gene. PMID- 1890406 TI - Culture of intact Sertoli/germ cell units and isolated Sertoli cells from Squalus testis: I. Evidence of stage-related functions in vitro. AB - As part of an ongoing program of research using the testis of the dogfish shark (Squalus acanthias) to characterize morphologic and functional changes during spermatogenesis, we have developed procedures for culturing intact spermatocysts (germ cell/Sertoli cell clones) and isolated Sertoli cells from premeiotic, meiotic, and postmeiotic stages of development. Phase contrast and light microscopy confirmed the stage and cellular composition of spermatocysts and showed that they retained their closed, spherical configuration for at least 15 d in culture. Stage-related variations in [3H]thymidine incorporation (premeiotic much greater than meiotic = postmeiotic) were observed, a pattern that was the same quantitatively and qualitatively after one or seven days of culture. [3H]Leucine-labeled protein synthesis was twofold greater in cultures with premeiotic spermatocysts than in cultures with more mature stages, whether medium or cysts were analyzed. Sertoli cells isolated from spermatocysts of different stages differed in size, shape, cytological appearance, ability to form flattened monolayers, and rate of DNA synthesis. One day after seeding, [3H]thymidine labeling of Sertoli cells corresponded to the pattern obtained with intact spermatocysts (premeiotic much greater than meiotic = postmeiotic); however, 7 days in culture effected a 40- to 200-fold increase in this parameter and altered the stage-dependent pattern (premeiotic = meiotic greater than postmeiotic). Also, when [3H]leucine-labeled macromolecules secreted by Sertoli cells from premeiotic versus meiotic stages were analyzed by polyacrylamide gel electrophoresis (PAGE), banding patterns differed. Initial results demonstrate the feasibility and potential of this in vitro system for studying qualitative and quantitative changes during spermatogenesis. PMID- 1890408 TI - Egg exudate-induced reduction of sperm lysin sensitivity in the vitelline coat after fertilization of Bufo japonicus and its participation in polyspermy block. AB - The jellyless eggs of Bufo japonicus or those from which the vitelline coats (VCs) had been removed (denuded eggs) were electrically activated. The exudate that accompanied egg activation (AEX) was collected to study its role in preventing polyspermy. When dejellied (but VC intact) eggs were treated with AEX, the eggs lost not only fertilizability but also the sensitivity of their VCs to the sperm lysin. By contrast, denuded eggs treated with AEX were fertilizable; even activated eggs were highly fertilizable, provided they were deprived of their VCs and inseminated 30 min after activation. The loss of sensitivity to sperm lysin occurred in VCs 3-5 min after activation either in De Boer's or 1/20 De Boer's solution. The activity of AEX to reduce the sensitivity of VCs to sperm lysin was heat-sensitive and dependent on Ca2+, but it was not affected at all by the variety of protease inhibitors used. The activity was lost by the preincubation of AEX with fragmented VCs in the presence of Ca2+, suggesting Ca(2+)-dependent binding of AEX molecules to the VC at fertilization. Immunocytochemical studies employing anti-AEX rabbit serum showed that the pertinent antigens were localized in the cortical granules of unfertilized eggs and in both the inner surface of VCs and the perivitelline space of fertilized eggs. We conclude that the AEX-induced loss of lysin sensitivity in VCs and the deposition of cortical granule materials on the inner wall of VCs constitute a slow and permanent block to polyspermy. PMID- 1890407 TI - Trypsin inhibitors prevent the progesterone-initiated increase in intracellular calcium required for the human sperm acrosome reaction. AB - Inhibitors of trypsin-like enzymes, benzamidine hydrochloride and 4' acetamidophenyl 4-guanidinobenzoate (also an inhibitor of other serine proteases), were tested for their effects on the acrosome reaction (AR) of human sperm initiated by progesterone or the calcium ionophore ionomycin. The AR was assayed by indirect immunofluorescence and transmission electron microscopy. The trypsin inhibitors, when added 10 min prior to stimulation by progesterone, significantly inhibited the AR in comparison with progesterone treatment alone. Transmission electron microscopic examination of the sperm after progesterone treatment indicated that the inhibitors blocked the membrane fusion events of the AR. By contrast, when ionomycin (at final concentrations of 3 microM) was added to sperm preincubated in inhibitors, sperm underwent morphologically normal AR, acrosomal matrix loss was not inhibited, and the percentage of acrosome-reacted sperm was the same as that obtained in the absence of inhibitors. Using the cell calcium indicator fura-2, we further demonstrated that both trypsin inhibitors prevented the progesterone-stimulated rise in intracellular Ca2+ ([Ca2+]int) required for the AR, but did not affect [Ca2+]int in unstimulated sperm. These results suggest that sperm trypsin-like activity may be directly or indirectly involved in increasing sperm [Ca2+]int during stimulation by progesterone. PMID- 1890409 TI - Low prevalence of human T-cell leukaemia virus-I and -II infection among drug users in Amsterdam, The Netherlands. AB - The prevalence of human T-cell leukaemia virus-I and -II infection was studied in a cohort of 346 intravenous and nonintravenous drug users in Amsterdam. Three participants (0.86%) had antibodies to HTLV-I by two commercially available HTLV I enzyme immunoassays (EIA). Infection in these three subjects was confirmed by radioimmunoprecipitation assay. In the immunoblot study, only two of the three subjects were considered positive, since the serum of the third subject had antibodies to p24 only. By means of the polymerase chain reaction two participants (male intravenous drug users infected with human immunodeficiency virus; HIV) appeared to be infected with HTLV-I and one subject (a male nonintravenous drug user from Surinam) with HTLV-II. It is concluded that HTLV-I and HTLV-II circulate sporadically among drug users in Amsterdam and that risky injecting behaviour, which led to an HIV epidemic among intravenous drug users, has not led so far to an appreciable transmission of the other retroviruses among this group. PMID- 1890410 TI - Characterisation of a series of human immunodeficiency virus isolates derived sequentially from a single patient. AB - Five HIV-1 isolates were obtained sequentially from a single seropositive individual during the later stages of AIDS. Four of these isolates were adapted to grow in a continuous human T-lymphocytic cell line. Comparative biological and biochemical studies of the virus isolates were made using persistently infected cultures or virus derived from these systems respectively. The data obtained clearly shows that viruses with different biological properties can be isolated from the same individual at different times during the course of clinical AIDS. PMID- 1890411 TI - Incidence of hepatitis B viraemia, detected using the polymerase chain reaction, after successful therapy of hepatitis B virus carriers with interferon-alpha. AB - Thirty-nine patients (62 sera) who, after interferon-alpha therapy for chronic hepatitis B virus (HBV) infection, were seronegative for HBeAg and HBV-DNA by dot blot hybridisation, were tested using the polymerase chain reaction (PCR) for residual viraemia. Overall, 59% of the HBsAg-positive sera and 43% of the HBsAg negative sera were positive by PCR. All except one of the HBsAg-negative patients had seroconverted to anti-HBs. Between 13 and 18 months after therapy, 33% of the HBsAg-positive and 20% of the HBsAg-negative patients remained viraemic. Eighteen months after the end of treatment, no patient tested was positive. Twenty-three patients were tested sequentially over periods from 1 to 43 months: Thirteen lost HBV-DNA by PCR, three remained positive, five remained negative, and two patients relapsed. The merits and disadvantages of PCR for assessing interferon treatment of HBV carriers are discussed. PMID- 1890412 TI - Natural seroconversion from hepatitis Be antigen to antibody among hepatitis B virus carriers in Okinawa Islands. AB - In the Okinawa Islands, the great majority of hepatitis B surface antigen (HBsAg) carriers have already acquired antibody to hepatitis Be antigen (anti-HBe) by the age of 30 years (preliminary cross-sectional data). To elucidate natural seroconversion from hepatitis Be antigen (HBeAg) to anti-HBe among HBsAg carriers found in the islands of Okinawa Prefecture, 34 HBeAg-positive HBsAg carriers were followed for 1-6 years with serial measurements of aminotransferase levels, HBeAg, and anti-HBe. The 34 subjects included 24 patients with chronic hepatitis (group 1) and ten asymptomatic HBsAg carriers (group 2). During the follow-up period, HBeAg disappeared from 14 subjects in group 1 with the cumulative clearance rate of HBeAg of 56.3% within the first 2 years and with 10 of the 14 subsequently developing anti-HBe. Moreover, the aminotransferases in 12 of the 14 spontaneously seroconverted fell into the normal range. The annual clearance rates of HBeAg among group 1 and group 2 were 25.6% and 9.3%, respectively. The tendency for early disappearance of HBeAg during a carrier's life time or in the course of chronic hepatitis may lead to the low death rate from hepatocellular carcinoma (HCC) particularly HCC associated with hepatitis B virus infection in this area. PMID- 1890413 TI - Autoantibodies during alpha-interferon therapy for chronic hepatitis B. AB - The development of autoantibodies and autoimmune reactions has been reported during and after interferon (IFN) therapy. Thirteen different antibodies from the sera of 32 patients with chronic hepatitis B treated with alpha-interferon (alpha IFN) were tested. Seventeen HBeAg-positive patients received 4.5 megaunits (MU) of recombinant IFN thrice weekly for 4 months, and 15 anti-HBe and HBV-DNA positive patients were treated with 5 MU/m2 of lymphoblastoid IFN thrice weekly for 6 months. Five patients (15%) had antinuclear antibodies (ANA) and one patient (3%) had smooth muscle antibodies before treatment. ANA appeared during IFN treatment in five (18%) of 28 previously negative patients. With discontinuation of treatment, the titer of ANA fell to undetectable levels in all patients. In contrast, none of the patients developed antibodies to endocrine organs, such as thyroid microsomal, thyroglobulin, parietal cells, pancreatic islet cell, and adrenal cortex antibodies or autoantibodies specifically associated with autoimmune liver disease such as liver kidney microsomal antibodies and antimitochondrial antibodies. There was no correlation between autoantibody positivity before therapy or autoantibody occurrence during treatment and response to IFN therapy. None of the patients developed clinical signs of autoimmune disease. These results indicate that these regimens of recombinant and lymphoblastoid IFN therapy of chronic hepatitis B are associated with a low risk of clinically significant autoimmunity. PMID- 1890414 TI - Neuron loss and addition in developing zebra finch song nuclei are independent of auditory experience during song learning. AB - In zebra finches early auditory experience is critical for normal song development. Young males first listen to and memorize a suitable song model and then use auditory feedback from their own vocalizations to mimic that model. During these two phases of vocal learning, song-related brain regions exhibit large, hormone-induced changes in volume and neuron number. Overlap between these neural changes and auditory-based vocal learning suggests that processing and acquiring auditory input may influence cellular processes that determine neuron number in the song system. We addressed this hypothesis by measuring neuron density, nuclear volume, and neuron number within the song system of normal male zebra finches and males deafened prior to song learning (10 days of age). Measures were obtained at 25, 50, 65, and 120 days of age, and included four song nuclei: the hyperstriatum ventralis pars caudalis or higher vocal center (HVc), Area X, the robust nucleus of the archistriatum (RA), and the lateral magnocellular nucleus of the anterior neostriatum (IMAN). In both HVc and Area X, nuclear volume and neuron number increased markedly with age in both normal and deafened birds. The volume of RA also increased with age and was not affected by early deafening. In IMAN, deafening also did not affect the overall age-related loss of neurons, although at 25 days neuron number was slightly less in deafened than in normal birds. We conclude that while the addition and loss of neurons in the developing song system may provide plasticity essential for song learning, these changes do not reflect learning.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1890415 TI - Nonspiking pathways antagonize the resistance reflex in the thoraco-coxal joint of stick insects. AB - In the stick insect (Carausius morosus) imposed forward and backward movements of the coxa of the middle leg induce resistance reflexes in the retractor or protractor coxae muscles, depending on the direction of movement. The hairs of the ventral coxal hairplate (cxHPv) function as the primary transducer of the retractor part of the underlying feedback loop: bending of the hairs of the cxHPv during an imposed forward movement of the coxa leads to a reflex activation of the retractor motoneurones, whereas releasing of the hairs causes an inhibition of these motoneurones. Local nonspiking interneurones were investigated, which transmit information from the cxHPv onto the retractor motoneurones: 1) they are depolarized during bending of the hair sensilla of the cxHPv and 2) they decrease the activities of retractor motoneurones. In addition, four of the interneurones drive a protractor motoneurone, when they are depolarized. As bending stimuli at the cxHPv (mimicking an imposed forward movement of the leg) induce reflex activation of the retractor motoneurones and reflex inhibition of the protractor motoneurones, the physiology of the recorded interneurones appears to antagonize the resistance reflex in the thoraco-coxal joint. The results indicate that these nonspiking interneurones take part in the shaping of the reflex response and that furthermore these interneurones are involved in the organization of the motor output to the two antagonistic sets of motoneurones. The possible role of these interneurones might be the adjustment of the gain and of the time constant in the thoraco-coxal feedback loop. PMID- 1890416 TI - Light-adapting migration of the screening-pigment in crayfish photoreceptors is a two-stage movement comprising an all-or-nothing initial phase. AB - The light-adapting response of the screening-pigment in crayfish retinal photoreceptors, previously described as a monophasic movement, was found to consist of two stages with different properties: (1) a rapid initial expansion that once started proceeds for at least half of the full distance, and (2) a slower and more variable continuation of the movement. The two components were resolved in isolated eyes stimulated under conditions expected to restrict Na+ influx into the photoreceptors. Only the second stage of the response to light was inhibited when Na+ was substituted with choline, or if the normal saline contained amiloride, a diuretic that hinders Na+ entry across many cell membranes. Amiloride in a medium without Na+ delayed, but did not curb, the first stage, whereas the rest of the movement was markedly restrained. Partial replacement of Na+ with Li+ blocked the second stage without affecting the rapid initial shift triggered by light. Exposure of dark-adapted eyes to high Na+ levels or to ouabain in the presence of Na+ in the dark also elicited a two staged pigment dispersion to the light-adapted position. Low Na+ concentrations or amiloride affected the latency, but not the rate or extent, of the first stage of migration in ouabain-treated eyes. Consistent though less significant results were obtained with cyanide and the Na+ ionophore monensin. These observations suggest a differential control of pigment position over two defined domains along the photoreceptors, probably to integrate a double mechanism of light-adaptation: an all-or-nothing partial shift of the pigment screen as a safety factor against overexposure, followed by a regulated adjustment according to stimulation intensity. PMID- 1890417 TI - A specific 70K protein found in epileptic rat cortex: induction of bursting activity and negative resistance by its intracellular application in Euhadra neurons. AB - The effect of 70-kD protein (P70, a specific protein found in cobalt-induced epileptogenic focus of rat cerebral cortex) on membrane properties was examined in identified neurons of the snail, Euhadra peliomphala, using the pressure injection method combined with the voltage-clamp technique. In neurons that normally exhibited spontaneous regular firing, intracellular injection of P70 elicited bursting activity and a negative slope resistance (NSR) region in their current-voltage (I-V) curve in a manner corresponding to the duration of its injection. These responses were suppressed by prior injection of an antibody to P70 into the neurons, and were markedly inhibited by a reduction of extracellular Na+ ions and the anticonvulsant agent phenytoin, but not by Co(2+)-substituted Ca(2+)-free saline. In addition, intracellularly applied P70 potentiated both bursting activity and the NSR induced by a Na channel activator, veratridine. However, prior application of a saturating dose of this activator occluded the effect of P70. These results suggest that P70 elicits a Na(+)-dependent negative resistance, which may contribute to the generation of bursting activity. PMID- 1890418 TI - An autoradiographic analysis of neurogenesis in juvenile Aplysia californica. AB - In developing Aplysia californica, a dramatic proliferation of new neurons occurs throughout the central nervous system (CNS) surprisingly late in juvenile development (Cash and Carew, 1989). In the present study, we investigated the source of these new neurons. Using tritiated thymidine autoradiography, we examined two different juvenile stages: stage 11 (before the large-scale proliferation) and stage 12 (at the peak of proliferation). Previous results implicated the body wall as a source for neurons in developing Aplysia (McAllister, Scheller, Kandel, and Axel, 1983; Jacob, 1984). Thus, we focused our attention on the body wall adjacent to a specific central ganglion, the abdominal ganglion. We found that in stage 11 there was uniform labelling of cells across the entire body wall. However, in stage 12 there was significantly more labelling in the body wall region immediately adjacent to the abdominal ganglion compared to flanking regions. Thus, at the time of neuronal proliferation, specific and highly localized regions of the body wall immediately opposite their target in the CNS show a significant increase in cell division. We also examined the distribution of labelled cells in the abdominal ganglion at survival times of 1 and 7 days after thymidine injection. In both stage 11 and stage 12, the fraction of labelled cells on the surface of the ganglion decreased over time, with a corresponding significant increase in the fraction observed on the inside. Our results support the hypothesis that specific regions of body wall are significantly up-regulated in juvenile Aplysia development, giving rise to widespread neuronal proliferation. These neurons then migrate from the body wall to their target ganglion, and from there continue migrating into the ganglion to achieve their final position. PMID- 1890419 TI - Induction of K-channel expression in a neuroblastoma cell line. AB - Whole-cell currents were examined in mouse neuroblastoma cells of the N2AB-1 line. In standard culture medium, N2AB-1 cells exhibited large voltage-dependent Na currents but no discernible K currents. Treatment of N2AB-1 cells with either dimethylsulfoxide (DMSO) in low-serum medium or with retinoic acid (RA) caused the expression of delayed rectifier K currents. Currents from two types of K channel with single channel slope conductances of 15.0 pS and 6.4 pS were observed in outside-out patches from cells of both treatment groups. Thus, while N2AB-1 cells did not exhibit K currents under standard culture conditions, they did possess the gene(s) encoding K channels. The treatments caused other changes that were not directly linked to K-channel expression. RA treatment caused neurite extension in most, but not all, N2AB-1 cells; however, all RA-treated cells, including those without neurites, expressed K currents. RA treatment did not suppress cell division or cause hypertrophy. In contrast, treatment with DMSO/low serum suppressed cell division and caused cellular hypertrophy, but did not cause long neurites to form. Thus, the regulation of K channels was not coupled in a simple fashion to properties that have been associated with a differentiated neuronal phenotype: neurite elaboration, changes in cell size, and inhibition of cell division. These results suggest that N2AB-1 cells may be a good model system for investigating the processes regulating K-channel expression. PMID- 1890420 TI - Regional specificity of developing reticulospinal, vestibulospinal, and vestibulo ocular projections in the chicken embryo. AB - The regional mapping of reticulospinal, vestibulospinal, and vestibulo-ocular neuron groups onto specific axonal pathways was determined in the chicken embryo by retrograde axonal tracing. Experiments were performed on in vitro preparations of the brain stem to allow for precisely localized tracer injections combined with selective lesions of axon tracts. Brain-stem neuron groups were labelled from 3 days of embryonic development, when the first reticulospinal axons reached the cervical spinal cord, to 9 days of embryonic development, when each of the three systems studied had acquired a relatively mature organization. A striking feature at all stages was the spatial segregation of many neuron groups that projected along different trajectories. Examples of such segregation were found for neuron groups projecting in the same tract on different sides of the brain stem, in different tracts on the same side of the brain stem, and rostrally versus caudally. The occurrence of this segregation from early stages suggests that the choice of projection pathway by many brain-stem neurons is in some way linked to cell position. In some regions of the brain stem, neuron groups projecting along different pathways are intermingled. At least some of this intermingling, however, appears to occur subsequent to the initial establishment of axon projection patterns. Comparison of the mapping patterns at progressively older stages, and with previous mapping in the 11-day-old embryo (Glover and Petursdottir, 1988; Petursdottir, 1990) suggests that these projections are established with little error. The one obvious example of remodelling involved the pontine reticulospinal projection, in which an early contralateral axon population appeared to retract from spinal to medullary levels over the course of a few days. A similar phenomenon may be involved in the elimination of part of the contralateral reticulospinal projection from the midmedulla. PMID- 1890421 TI - Nerve growth factor (NGF) induces sprouting of specific neurons of the snail, Lymnaea stagnalis. AB - Nerve growth factor (NGF) was examined for its ability to elicit sprouting by adult molluscan neurons. Motoneurons and interneurons (but not neurosecretory cells) from Lymnaea exhibited a sprouting response to murine 2.5S NGF in defined medium with a half-maximal response at about 150 ng/mL. Furthermore, an NGF antiserum blocked sprouting by all normally responsive neurons. We tested whether an NGF-like molecule is a component of conditioned medium (CM) by attempting to preabsorb its sprout-inducing activity with NGF antiserum. Treatment of CM with immune (but not nonimmune) serum largely blocked the response of motoneurons, but not that of neurosecretory cells, to CM. We conclude that NGF exerts neurotrophic activity on specific adult Lymnaea neurons, and suggest the possibility that an NGF-like molecule may exist in the molluscan nervous system. PMID- 1890422 TI - R15 alpha 1 and R 15 alpha 2 peptides from Aplysia: comparison of bioactivity, distribution, and function of two peptides generated by alternative splicing. AB - The mRNA precursor encoded by the R15 gene is alternatively spliced in different neurons to form two related variants, R15-1 and R15-2 mRNA. One of the peptides encoded by the R15-2 mRNA, the R15 alpha 1 peptide, is expressed in the endogenously bursting neuron R15 and mediates some of its central and peripheral synaptic actions. In this study we found that the R15 alpha 2 peptide, which is encoded by the R15-1 mRNA, is synthesized in other neurons in the abdominal ganglion and is also bioactive. The R15 alpha 1 and R15 alpha 2 peptides were found to exert many similar actions on the cardiovascular, digestive, respiratory, and reproductive systems. However, the differences between many of the pharmacological effects of the R15 alpha 1 and R15 alpha 2 peptides indicate that alternative splicing in this system results in two functionally different peptides. Widespread immunoreactivity was found for an antibody directed against the R15 alpha 2 peptide, both in the central nervous system and the periphery. But because of the shared sequence with the R15 alpha 1 peptide, the antibody cross-reacts with the R15 alpha 1 peptide. To distinguish immunocytochemically between the two peptides, we also raised a second antibody that recognizes only the R15 alpha 1 peptide. This antibody labeled the cell body of only one neuron in the central nervous system, R15, although widespread immunoreactivity was found in axons and varicosities in the periphery. PMID- 1890423 TI - Development and modulation of endogenous bursting in identified neuron R15 of juvenile Aplysia. AB - Evidence from a variety of both vertebrate and invertebrate preparations has demonstrated that modulation of the intrinsic firing patterns of individual neurons can have a dramatic effect on the functional output of a neural circuit. Although the mechanisms underlying the production and modulation of intrinsic firing patterns have been extensively studied in adult nervous systems, relatively little is known about how these two features of intrinsically active neurons develop. To address these issues, we have examined the development of endogenous bursting and its modulation by neuropeptides in the identified cell R15 of juvenile Aplysia. Confirming Ohmori (1981), we found that the mature parabolic bursting pattern of R15 is absent in early juvenile stages and develops only gradually over the last stage of juvenile development. We have then analyzed the modulatory effects of extracts made from the neurosecretory bag cells of Aplysia on the immature firing pattern of juvenile R15 cells. In the adult, neuroactive peptides released from the bag cells are known to intensify bursting. In juveniles, we have found that bag cell extract (BCE) can induce bursting prematurely as well as intensify immature bursts, whereas control extracts have no effect on the firing pattern of R15. These results show that the ionic currents necessary for the generation of endogenous bursting in R15 are present and can be modulated before the normal developmental expression of the burst pattern. PMID- 1890424 TI - Laminin-like immunoreactivity in the snail Helisoma: involvement of approximately 300 kD extracellular matrix protein in promoting outgrowth from identified neurons. AB - Polyclonal antibodies directed against laminin (LM), and against the A and B chains of reduced LM were used to identify antigenically related proteins in the extracellular matrix (ECM) of the snail Helisoma trivolvis. Immunofluorescence of snail central ganglionic rings using either the anti-LM or anti-B chain antibodies labeled the ECM within ganglionic sheaths as well as basal laminae surrounding the ganglia. Both the anti-LM and anti-B chain antibodies recognized a prominent, approximately 300-kD protein on immunoblots of a snail central ganglion preparation enriched in ECM components. The anti-A chain antibody failed to label any structures in sections of snail ganglia or to recognize any proteins on immunoblots of ganglionic ECM. A polyclonal antibody was raised against the approximately 300-kD snail protein. Immunofluorescence of snail ganglia with the anti- approximately 300-kD antibody gave a distribution of labeled structures comparable to that obtained with the anti-LM antibody. Immunofluorescent labeling of sections of snail muscle and salivary gland with the anti- approximately 300 kD antibody revealed a distribution of reactive protein characteristic of an ECM component. Probing immunoblots of ganglionic ECM with the anti- approximately 300 kD antibody revealed the recognition of the same approximately 300-kD protein as identified by the anti-LM antibodies. Media conditioned by Helisoma central ganglionic rings (CM) contains an unidentified neurite outgrowth promoting factor (NOPF). Immunoblots of CM probed with the anti-B chain and anti- approximately 300-kD antibodies reveal the recognition of a soluble approximately 300-kD protein similar to the approximately 300-kD protein identified in snail ECM. The ganglionic ECM preparation containing the approximately 300-kD protein supported outgrowth from cultured snail buccal neurons B5, and addition of anti- approximately 300-kD Fab fragments to CM abolished its outgrowth promoting activity. These results suggest that the approximately 300-kD ECM protein may be the NOPF in CM and/or functions in promoting neurite outgrowth. PMID- 1890425 TI - Development of paleocortical projections through the anterior commissure of hamsters adopts progressive, not regressive, strategies. AB - The perinatal development of anterior commissure projections was studied in hamsters by use of carbocyanine crystals implanted either into the commissure or into the ventrolateral prosencephalon. The earliest fascicles of growing commissural fibers had reached the midline on day 14 of gestation (E14). On E15, these fibers had entered the opposite hemisphere and reached the borders of their target regions. No waiting period was observed, since on E16 axons were already collateralizing into most targets. On P1, labelled cells were seen in all regions projecting through the anterior commissure in adults, namely, the anterior olfactory nucleus, olfactory tubercle, piriform cortex, nucleus of the lateral olfactory tract, bed nucleus of the stria terminalis, insular, perirhinal, entorhinal, and temporal cortices, as well as the amygdaloid complex. No evidence of topographical exuberance was detected. Counts of labelled neurons showed that the number of commissural cells increased gradually after birth. It is concluded that the development of paleocortical connections through the anterior commissure employs progressive strategies, lacking the regressive phenomena that are characteristic of the neocortical projections through the corpus callosum. PMID- 1890427 TI - Transneuronal induction of muscle atrophy in grasshoppers. AB - Autotomy is a process in grasshoppers whereby one or both hindlimbs can be shed to escape a predator or can be abandoned if damaged. It occurs between the trochanter and the femur (second and third leg segments) and once lost, the legs never regenerate. Autotomy severs branches of the leg nerve (N5) but damages no muscles since none span the autotomy plane. We find, however, that undamaged muscles intrinsic to the thorax of grasshoppers, Barytettix psolus, atrophy to less than 15% of their normal mass after autotomy of a hindlimb. These muscles operate the coxa and trochanter (first and second leg segments) and are innervated by branches of nerves 3 and 4; nerve branches that are not damaged by autotomy. Atrophy is localized to the side and body segment where autotomy occurs. Atrophy is evident 7-10 days after loss of a limb, is complete by about 30 days, and follows a similar time course whether induced in young adult, or sexually mature grasshoppers. During autotomy, leg nerve 5 is served distal to the trochanter, the thoracic muscles lose their normal static and dynamic load, and these muscles are subsequently no longer used to support the weight of the insect during posture and locomotion. Experimental loading and unloading of the affected muscles, and cutting of nerves indicated that it is the severing of leg nerve 5 during autotomy that transneuronally induces muscle atrophy. PMID- 1890426 TI - A comparison of calcium homeostasis in isolated and attached growth cones of the snail Helisoma. AB - This study examines the capability of growth cones from identified neurons of the snail Helisoma trivolvis to perform calcium homeostasis. Calcium influx into the cytoplasm was eliminated or increased experimentally to alter [Ca]i, and the compensatory response of the growth cone was measured with the fluorescent calcium indicator Fura-2. Growth cones compensated for both increases and decreases in calcium influx by restoring [Ca]i towards basal levels under both types of challenges. The intrinsic ability of growth cones to control [Ca]i was examined in physically isolated growth cones. Isolated growth cones demonstrated essentially identical calcium homeostatic properties to their intact counterparts, indicating that mechanisms governing calcium homeostasis exist intrinsically in the growth cone. Such independence may add significantly to the growth cone's potential to locally interpret and respond to stimuli encountered en route to its appropriate target. PMID- 1890429 TI - Epidemiology in Plato's cave: claims data and clinical reality. PMID- 1890428 TI - Physiological and developmental implications of motor unit anatomy. AB - There is increasing evidence that the architectural design and arrangement of the fibers within a motor unit have important physiological and developmental ramifications. Limited data, however, are available to directly address this issue. In the present study the physiological properties of one motor unit in each of seven cat tibialis anterior (TA) muscles were determined. Each of these units then was repetitively stimulated to deplete the glycogen in all muscle fibers within the unit. Subsequently, the length, type of ending, and spatial distribution of fibers sampled from these physiologically and histochemically typed motor units were determined. Four fast fatigable (FF), one fast, fatigue resistant (FR), and two slow (S) motor units (MU) were studied. The samples consisted of all those glycogen-depleted fibers (9-27) contained within a single fascicle or a circumscribed area of each of the motor unit territories. The mean fiber lengths for the two slow motor units were 35.9 and 45.5 mm. The mean fiber lengths for the fast motor unit samples ranged from 8.8 to 48.5 mm. Some fibers of both the fast and slow units reached lengths of 58 mm. Most of the fibers in the slow units extended the entire distance between the proximal and distal musculotendinous planes, had relatively constant cross-sectional areas, and terminated at the tendon as blunt endings. In contrast, the majority of the fibers in the fast units terminated intrafascicularly at one end, and the cross sectional area decreased progressively along their lengths, that is, showed a tapering pattern for a significant proportion of their lengths. Therefore, the force generated by units that end midfascicularly would appear to be transmitted to connective tissue elements and/or adjacent fibers. All fibers of a fast unit within a fascicle were located at approximately the same proximo-distal location. Thus, developmentally the selection of muscle fibers by a motoneuron would seem to be influenced by their spatial distribution. The architectural complexities of motor units also have clear implications for the mechanical interactions of active and inactive motor units. For example, the tension capabilities of a motor unit may be influenced not only by the spatial arrangement of its own fibers, but also by the level of activation of neighboring motor units. PMID- 1890430 TI - Comparing clinical information with claims data: some similarities and differences. AB - How well can hospital discharge abstracts be used to estimate patient health status? This paper compares information on comorbidity obtained from hospital discharge abstracts for patients undergoing prostatectomy or cholecystectomy at a Winnipeg teaching hospital with clinical data on preoperative medical conditions prospectively collected during an Anesthesia Follow-up study. The diagnostic information on cardiovascular disease, respiratory disease, and metabolic disorders showed considerable agreement, ranging from 65 to over 90% correspondence across the two data sets. Certain conditions noted by the anesthesiologist were often absent from the claims data; cardiovascular disease was recorded in the clinical data but absent from the claims for 31% of prostatectomy and 17% of cholecystectomy cases. Such patients were less likely to have been assigned a high score on the ASA Physical Status measure or to have high-risk diagnoses on the hospital file. Similar findings resulted from comparing the two sources in their ability to predict such adverse outcomes as mortality and readmission to hospital: the anesthesia file generally included less serious comorbidity. PMID- 1890431 TI - Inequalities in health in intensive care patients. AB - In order to study the possible association between socioeconomic status (SES) and critical care mortality, we examined a cohort of 847 patients over 14 years of age, as they were consecutively admitted to three general intensive care units (ICUs). The patients with low SES (social classes IV and V according to the British Registrar General's classification) were older (62.0 v 58.5 years old, p less than 0.0001) and showed a higher ICU mortality (odds ratio (OR) = 1.61, p = 0.0204) and severity of illness on admission (mean Simplified Acute Physiology Score [SAPS] 9.9 vs 8.7, p = 0.0002) than patients with high SES (social classes I-III). The initial severity of illness differential was detected both in patients admitted from the emergency area and in patients admitted from the general hospitalization ward, suggesting the existence of some kind of preselection procedure related to the SES of the patient. The stepwise logistic regression analysis identified as independent predictive variables of ICU mortality therapeutic effort (measured with the Therapeutic Intervention Scoring System [TISS]), SAPS score, age and hospital, but not SES. The TISS/SAPS ratio according to origin of patients (emergency/general wards) was comparable in the high and low SES. We conclude that there is an inverse relationship between SES and ICU mortality. The mortality excess in the low SES patients is largely accounted for by the covariates of the low SES (especially their high age and severity of illness on admission). There is no evidence of a different relative therapeutic effort according to the SES. PMID- 1890432 TI - The epidemiology of exposure to electromagnetic fields: an overview of the recent literature. AB - Epidemiologic studies of exposure to electromagnetic fields (EMF) have been reviewed. Possible links to incidences of cancer and abnormal fetal development have been suggested by some investigators. In general, the results have been inconsistent. There are many deficiencies in the studies, and many questions have been raised about the validity of some of the conclusions proposed. There is currently no definitive evidence of an association between exposure to EMF and the alleged risks. Due to problems and limitations inherent in future studies (misconceptions about exposure levels, uncertainty about field variability, criticisms of surrogate measures), this question is unlikely to ever be answered with certainty. Unfortunately, many highly-publicized accounts of speculative and unsubstantiated claims have caused undue concern among the general public. PMID- 1890433 TI - The hospital costs of diagnostic procedures for colorectal cancer. AB - Diagnosis for colorectal cancer is commonly made using either colonoscopy or double contrast barium enema techniques. To data, little attention has been paid to the comparative costs of these two procedures and the paper presents estimates of hospital costs for each, using data from the colorectal study being undertaken in Nottingham, U.K. Consideration is also given to procedure sensitivity and the frequency of referral to the alternative technique in cases of incomplete diagnosis. The paper presents the conditions under which a given technique may be considered cost-superior to its alternative but concludes that the absence of conclusive clinical trial data and other considerations precludes the identification of a definitively optimum technique from the economic point of view. PMID- 1890435 TI - Risk factors for subarachnoid hemorrhage in a longitudinal population study. AB - The known risk factors of atherosclerotic diseases may be involved in the development of a subarachnoid hemorrhage. We studied the morbidity and mortality due to subarachnoid hemorrhage among 42,862 men and women aged 20-69 years who had participated in a large health survey in Finland. During a mean follow-up of 12 years, 102 non-fatal and 85 fatal cases of subarachnoid hemorrhage were observed. The total incidence was 37 per 100,000 person-years. Smoking and hypertension were positively associated and body mass index was inversely associated with the risk of subarachnoid hemorrhage. These associations were not confounded by age or each other. No statistically significant association with risk was detected for serum cholesterol level, hematocrit content, known heart disease, or diabetes. The risk was especially elevated among lean hypertensive subjects and lean smoking subjects. The age-adjusted relative risks of subarachnoid hemorrhage for lean, hypertensive smokers were 18.3 (95% confidence interval (CI), 7.8-42.7) among women and 6.7 (95% CI, 2.3-19.7) among men as compared to the risk among subjects without these risk factors. We conclude that modifiable risk factors are predictive of subarachnoid hemorrhage, for which reason subarachnoid hemorrhage may in part be preventable. Leanness combined with arterial hypertension and/or smoking, in particular, poses a substantially elevated risk. PMID- 1890434 TI - Latency and time-dependent exposure in a case-control study. AB - Detailed historical data are elicited often from subjects in retrospective studies, yielding time-dependent measures of exposures. Investigation of a hypothesized period of latency can be made by examining disease/exposure relationships in multiple time windows, either along the age or time-before diagnosis axes. We suggest splitting the data into many time intervals and separately fitting regression models to the available data in each interval. Covariances between estimated coefficients from different intervals are empirically estimated, and used for assessing variability of specified functions of the time-specific coefficients. Alternative methods of interval formation and their consequences are discussed. We apply these methods to a French case-control study of oral contraceptive use and cervical cancer incidence, and compare the results to those of standard analyses. PMID- 1890436 TI - Does alcohol protect against the formation of gallstones? A demonstration of protopathic bias. AB - Previous studies have found an inverse relation between alcohol use and clinical gallstone disease, suggestive of a protective effect of alcohol use. However, such an inverse relation may (at least partly) be explained by a reduction of alcohol use because of symptoms related to clinical gallstone disease (protopathic bias). We empirically evaluated the consequences of different designs for the avoidance of such bias in a series of case-control studies. A first study deliberately used a design that is commonly seen in the literature. Cases of clinical gallstone disease, referred to hospital because of symptoms, were contrasted with general population controls. The results suggested an inverse relation between alcohol use and gallstones. Next, three alternative case control studies were performed using designs that safeguard against protopathic bias. In none of these studies was an association between alcohol use and gallstones found. This demonstrates the probable existence of protopathic bias in case-control studies on alcohol use and gallstones. It is argued that earlier non experimental studies on this topic were susceptible to such bias. This has most likely led to an overestimation of the protective effect. PMID- 1890438 TI - A simple model-based index of abdominal adiposity. PMID- 1890437 TI - Intra- and interindividual variability of glucose tolerance in an elderly population. AB - The intra- and interindividual variability of the oral glucose tolerance test (OGTT) and other risk factors was investigated in 237 subjects, aged 64-87, examined annually in the period 1971-1975. Coefficients of intraindividual variation (CVa) were calculated from individual regressions on time. The lowest CVa was found for the summary index including fasting glucose (area under the curve, AUC): 10.0 +/- 4.9%. For fasting and 30, 60, and 120 min glucose the values ranged from 12 to 18%. The CVa's were not associated with age, gender, drug use, and disease prevalence, and may also be applied to other populations. The reliability coefficient depended on the prevalence of diabetes in the population and was higher than observed in younger populations. The highest reliability coefficient was observed for AUC: 0.81. For the combined information of OGTT, reflected by AUC or by classification according to WHO criteria, the variability was comparable to that of other cardiovascular risk factors such as serum total cholesterol. PMID- 1890439 TI - The second best in statistics. AB - When estimating a parameter, it may not be possible to remove all sources of bias. Yet a priori we do not know whether eliminating some sources will improve or worsen the estimate. PMID- 1890440 TI - White blood count and hypertension. PMID- 1890441 TI - Clinical epidemiology and the use of words. PMID- 1890442 TI - Diagnostic tests are not always black or white: or, all that glitters is not [a] gold [standard]. PMID- 1890443 TI - Evaluating the human engineering of microprocessor-controlled operating room devices. AB - Although human engineering features are widely appreciated as a potential cause of operating room incidents, evaluating the human engineering features of devices is not widely understood. Standards, guidelines, laboratory and field testing, and engineering discipline are all proposed methods for improving the human engineering of devices. New microprocessor technology offers designers great flexibility in the design of devices, but this flexibility is often coupled with complexity and more elaborate user interaction. Guidelines and standards usually do not capture these features of new equipment, in part because technology improvements occur faster than meaningful guidelines can be developed. Professional human engineering of new devices relies on a broad, user-centered approach to design and evaluation. Used in the framework of current knowledge about human operator performance, these techniques offer guidance to new equipment designers and to purchasers and users of these devices. PMID- 1890444 TI - Measurement of tissue oxygen tension: comparison between two subcutaneous oxygen tonometers. AB - We compared the 95% response time (95% RT) of two tissue oxygen tonometers under two sets of circumstances. We first evaluated the devices during normoxia, hyperoxia, and anoxia in vitro, using a transcutaneous PO2 electrode (PtcO2) as the reference. The responses to normoxia and to different grades of hyperoxia were examined in vivo in 8 healthy volunteers to assess the relationship between changes in subcutaneous PO2 and PtcO2, an estimate of arterial PO2 (PaO2). One subcutaneous method (ScA) used a technique based on a polarographic needle electrode in situ connected to an ammeter; the second method (ScB) was based on a blood gas analyzer system first described by Hunt (Lancet 164;2:1370). ScA and PtcO2 both responded to stepwise changes in ambient oxygen concentration (21 100%) in vitro within 10 seconds; the 95% RT of ScA was 1.39 +/- 0.5 to 2.39 +/- 0.8 minutes and that of PtcO2 was 0.32 +/- 0.1 to 0.49 +/- 0.1 minutes. ScB had a lag of 3 minutes, and the 95% RT was 6.75 +/- 0.5 to 8.2 +/- 0.8 minutes. In contrast to the results in vitro, the response of ScA to changes in FiO2 in vivo was delayed compared with the rapid response of PtcO2, reflecting the physiologic delay of tissue PO2 in response to increased PaO2. The time lag and the long 95% RT of ScB were even more evident in vivo. ScA reacted three to four times faster than ScB, both in vitro and in vivo, to changes in the oxygen environment. The in vitro 95% RT of ScA to changes in ambient oxygen varied from 2 to 3.5 minutes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1890445 TI - Auscultation cannot distinguish esophageal from tracheal passage of tube. AB - We quantitatively compared the acoustic characteristics of passage of an endotracheal tube into the trachea with those of passage into the esophagus by analyzing the loudness and frequency (90% spectral edge frequency) of the sounds when auscultated at the suprasternal notch. We found that there was a significant difference (P less than 0.01) in maximum loudness between esophageal and tracheal intubations (0.15 +/- 0.05 and 0.25 +/- 0.06 V, respectively). However, there were no significant differences between the 90% spectral edge frequencies. We conclude that, without directly comparing the maximal acoustic amplitude of tracheal intubation with that of esophageal in each patient, one cannot distinguish between the two types of intubation by means of auscultation. PMID- 1890446 TI - Use of long catheters for multipatient anesthetic monitoring at high respiratory frequencies. AB - Anesthetic gases from several patients can be monitored simultaneously with a centrally located mass spectrometer. Such monitoring requires catheters from patient to spectrometer that are several meters long. Scamman (J Clin Monit 1988; 4:227-229) found that when the respiratory frequency is high, as with infants, the CO2 signal from the patient is unacceptably distorted during passage down the catheter. This is due to Taylor dispersion of the input signal. An outline of the theory of Taylor dispersion is given. The equations describe the interaction between the velocity distribution (which, in laminar flow, is parabolic) and the radial diffusion of CO2. This interaction keeps a tracer signal together in a pulse, as it moves down the tube with the mean velocity, spreading somewhat as it proceeds. How much does an initially sharp signal become blurred? The spread of such a signal when it reaches the detector, measured in time, can be expressed in various ways. Measurement is complicated, however, by the fact that the gas pressure may fall by as much as a factor of 10 along the line. The resultant expansion and acceleration of the gas cannot be ignored. A full treatment of this complication is given elsewhere, but the following simple equation is described: delta t = 3.54 x 10(-3) l [(1 + R2)/(1 - R2)]1/2. Typically, the spread time is up to a quarter of a second for catheters of 50 m, such as used by Scamman. This is comparable with the period of CO2 rise and fall for infants and explains the serious distortion in wave form that Scamman+ found.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1890447 TI - A clinical evaluation of rapid automatic noninvasive blood pressure determination with the Ohmeda 2120 "return-to-flow" method. AB - Most commercial noninvasive blood pressure devices use the oscillometric method for determination of blood pressure. The Ohmeda 2120 noninvasive blood pressure monitor uses the oscillometric technique, but it also includes a "Sys Stat" mode for rapid determination of systolic blood pressure up to ten times per minute. This Sys Stat mode uses the "return-to-flow" method, in which the pressure on an upper arm cuff decreases in small steps until a finger sensor detects the first pulse of blood. Data from 16 patients monitored with the Ohmeda 2120 unit and with an arterial cannula were analyzed. The line of regression was Sys Stat = 0.85 (arterial) + 9.49. The Ohmeda 2120 monitor tended to underestimate the arterial pressure, particularly at higher pressures. Several factors could have contributed to this underestimation. Even so, the accuracy is sufficient for clinical use under most circumstances. More importantly, in an urgent situation, the Sys Stat mode can provide a reading of systolic blood pressure within seconds. PMID- 1890448 TI - A prospective study of intraoperative pulse oximetry failure. AB - Since pulse oximetry is now an ASA standard for intraoperative monitoring, we sought to determine the intraoperative failure rate for this device. We prospectively evaluated the intraoperative failure rate of our pulse oximeters at the four University of Washington Hospitals (University of Washington Medical Center, Veterans Affairs Medical Center [VAMC], Children's Hospital and Medical Center, and Harborview Medical Center [HMC]) recorded from April 1989 to August 1989. We defined failure as the inability to obtain any oximetry reading for a cumulative period of more than 30 minutes during any anesthetic procedure after all equipment malfunctions had been eliminated. Our puse oximeters failed in 124 of 11,046 cases studied; this is a failure rate of 1.12%, which ranged from 0.56% at HMC to 4.24% at VAMC. The failure rate at VAMC (4.24%) was significantly higher than the other hospitals (p less than 0.001). Those cases associated with the pulse oximeter failure had the following characteristics: (1) an ASA status of 3 or higher, (2) lengthy operations, and (3) elderly patients. When the device did fail in a patient, it did not function for 32% of the mean anesthesia time. We conclude that the intraoperative use of the pulse oximetry can provide information about blood oxygen saturation in most patients. However, in approximately 1% of the patients we studied in the operating room, mechanically functioning pulse oximeters failed to provide readings of blood oxygen saturations during routine operative use. PMID- 1890449 TI - Use of neural network analysis to classify electroencephalographic patterns against depth of midazolam sedation in intensive care unit patients. AB - The electroencephalographic (EEG) analog signal is complex and cannot easily be described by univariate variables. Clear visual changes in the EEG power spectrum can be present with little or no change in univariate variable values. A method that could produce a single value based on the total data available in the EEG power spectrum would be very useful in monitoring EEG changes. Neural network analysis is a technique that can take multiple inputs and produce a single output value using complicated processing patterns that require training to establish. We examined the usefulness of a series of neural network models to classify 63 EEG patterns against sedation level in 26 mechanically ventilated patients requiring midazolam for long-term sedation. During a stable period of sedation, a 4- to 60-minute period of EEG data was obtained concurrently with a sedation level from 1 (follows commands) to 7 (no or gag response to suctioning of the endotracheal tube). The EEG power spectrum was divided into equal frequency bands, and the log absolute powers in each of these bands were used as inputs for a series of neural network models. The output target was the sedation level associated with each set of EEG data. Networks were trained on a subset of EEG power/sedation score data pairs, and the ability to classify the remaining data pairs was tested. Using a t-test comparison with a random set of sedation levels, we found that trained neural network models classified EEG patterns against sedation level successfully (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1890450 TI - Linking mass spectrometers to provide continuing monitoring during system failure. AB - Although multipatient monitoring with a time-shared mass spectrometer provides considerable cost advantages, failure of one component in a shared system can disrupt gas monitoring at all sites. We describe a simple method for linking two central mass spectrometer systems to provide continual monitoring during failure of one unit, without the need for time-consuming reconfiguration of individual patient sample line and display connections. PMID- 1890452 TI - Acid-base balance controversy. Case for standard-base excess as the measure of nonrespiratory acid-base imbalance. PMID- 1890451 TI - Acid-base balance controversy. Editorial introduction. PMID- 1890454 TI - Blood pressure monitoring in infants. PMID- 1890453 TI - Acid-base balance controversy. Total-body carbon dioxide titration. PMID- 1890455 TI - The control mechanism involved in post-subarachnoid hemorrhage vasospasm. AB - In the present work the main relationships among cerebral blood volume (CBV), cerebrospinal fluid (CSF) dynamics, cerebral blood flow (CBF) and cerebrovascular reactivity following subarachnoid hemorrhage are critically examined and discussed. It is hypothesized that, following the rupture of an aneurysm, antagonistic mechanism which regulate CBF (through a vasodilatation of the arteriolar vessels) and CBV (through a constriction of basal intracranial arteries) are activated, due to the initial increase in intracranial pressure (ICP) the time pattern of ICP and cerebral hemodynamics in the following days can be largely different depending on the state of CSF dynamics. When the CSF outflow is not altered by blood in the subarachnoid space ICP suddenly returns to the basal value, and a normal cerebral hemodynamics is rapidly restored. By contrast, in conditions in which the normal CSF dynamics is impaired, the opposite action of mechanisms regulating CBF and CBV may lead to instability of the cerebrovascular bed, with the result of a maximal dilatation of pial vessels and a strong constriction of basal arteries (spasm). In our opinion the phenomenon of vasospasm can be better understood if the reactivity of basal intracranial arteries is analyzed as a part of the complex physiological system of cerebrovascular regulation. PMID- 1890456 TI - Traumatic fractures of the craniovertebral junction. Management of 23 cases. AB - Twenty-three consecutive cases of traumatic C1-C2 fractures treated at the Department of Neurosurgery, University of Milano, are reported. Of these there were 13 cases of odontoid fractures, 6 hangman fractures, 2 anterior inferior corner fractures, 2 atlas-axis combination fractures and 2 Jefferson fractures. Almost all the patients were young people involved in motor vehicle accidents. Nineteen patients were treated with external immobilization (halo vest, Minerva) for 3-6 months while 4 odontoid fractures underwent early surgical posterior stabilization. At follow-up, 20 patients had a good fusion while 3, aged over 75 years, died due to cardiopulmonary or septic complications. The appropriate management of this type of lesion is still a matter of discussion. In our opinion the Halo device allows good stabilization after correct fracture reduction. PMID- 1890457 TI - Medulloblastoma in adulthood. AB - Reporting 32 cases of medulloblastoma in patients aged 17 to 65 years and reviewing the major case-series in the literature, we analyze the clinicobiological and diagnostic features and treatment of this tumor in adulthood. We consider some factors that seem to have a favorable bearing on the prognosis: female sex, length of clinical history, tumor size, hemispheric site, and total removal followed by radiotherapy. We then discuss the differences in tumor behavior between adulthood and childhood that emerged from the comparative analysis. PMID- 1890458 TI - Cavernous angioma of the spinal dura. AB - Three cases of cavernous angioma of the spinal dura are reported. Two of them were extradural and located in the thoracic segment. One was intradural and situated in the cervical tract. There seem to be no other cases reported in literature. Their clinical presentation was in no way different from that of the much more common neurinomas and meningiomas. PMID- 1890459 TI - Trigeminal cystic neurinoma of the posterior fossa. Case report. PMID- 1890460 TI - Diagnosis and treatment of pituitary adenoma with adjacent carotid artery aneurysm. AB - We present three cases of pituitary adenoma with adjacent carotid artery aneurysm. The three adenomas are HGH-producing, prolactinoma and non-functioning tumors. Two of these 3 patients showed signs and symptoms of adenoma, while the other one showed a subarachnoid hemorrhage (SAH). The presence of the aneurysm adjacent to the pituitary adenoma was strongly suspected by the MRI finding, and the flow void signal sign just attached to the carotid artery in acromegalic patient. In a case of recurrent pituitary adenoma, development of the aneurysm was observed at a 17 year interval between angiography. Although the etiology of these lesion is not yet known, the change of hemodynamism seemed to have a major role in producing the aneurysm in all cases. The simultaneous treatment of the pituitary adenoma with aneurysm produced good results in all patients by the frontotemporal approach. MRI proved to be quite a useful tool in the management of cases of pituitary adenoma with adjacent carotid artery aneurysm. Cerebral angiography should also be performed without hesitation in such cases in which the MRI shows a significant finding of aneurysm. Simultaneous treatment of these lesions by a frontotemporal approach is recommended. PMID- 1890461 TI - Surgically treated intracerebral hematoma in a child with Henoch-Schonlein purpura. AB - The authors present a boy with a sudden onset a large intracranial hematoma causing rapid neurologic deterioration. The hematoma resulted from intraparenchymal bleeding due to Henoch-Schonlein purpura. Urgent surgical removal of the hematoma was followed by excellent improvement of the patient. PMID- 1890462 TI - Late intraneural metastasis of the brachial plexus from mammary carcinoma. Report of a case. AB - A rare case of late intraneural metastasis of the brachial plexus from mammary carcinoma is reported. The lesion was strictly intraneural and had a latency of 29 years and the diagnosis was made incidentally in the course of surgery. The clinicopathological and diagnostic features of the tumor are discussed in the light of the accessible literature. PMID- 1890465 TI - Fetal protection and maternal-fetal medicine. AB - Section 2.01 of the Fetal Protection Act of 1999 defines "qualified patient" as one who registers a pregnancy by six weeks of gestational age. Section 2.02 requires that a patient be "qualified" before receiving financial aid. Similarly, all private third party payers require "registration" of the pregnancy by six weeks. "Registration" consists of proof of intrauterine pregnancy by ultrasound and attachment of a telemetry device to the cervix. Such a device will monitor the patient's vital signs, contractions, fetal movement and levels of various "toxins" in the maternal blood. Toxins include but are not limited to alcohol, nicotine, controlled substances as well as excess levels of salt, carbohydrates and saturated fats. Unacceptable variations in telemetry will trip an alarm at the patient's approved prenatal care center. Such an alarm will trigger a visit from an agent from the Fetal Bureau of Investigation. PMID- 1890464 TI - Treatment and long-term follow-up results of prolactin secreting pituitary adenomas. AB - The authors have reported data on a retrospective study, carried out in order to evaluate the short- and the long-term follow-up results of transsphenoidal microsurgery for prolactin-secreting pituitary adenomas; and to point out the indications for an eventual additional bromocriptine treatment. Prior to surgery, the patients were tested according to the study protocol. Patients were grouped differently according to their adenoma size. We found a good correlation between adenoma size and hormonal values. The surgical treatment led to an immediate endocrine cure in 47 patients (48.9%), with the majority occurring in microprolactinomas. Post-operatively, the cure rate was maintained in 45 patients. The Authors deem the transphenoidal microsurgery the therapy of first choice for microadenoma and mesoadenoma treatment, especially whenever there is bromocriptine intolerance. On the contrary, in invasive macroadenomas, bromocriptine is a necessary additional therapy both to shrink large tumors sufficiently for subsequent transsphenoidal approach and in incompletely removed tumors or persistent hyperprolactinemia. PMID- 1890463 TI - Intracranial metastases to the pineal region. Report of three cases. AB - The pineal region is one of the rarest sites in the brain for metastatic involvement of systemic malignant tumors. A review of the literature shows that approximately 70 such cases have been reported previously, and most of them were diagnosed by autopsy. In this brief report we describe three cases of isolated intracranial metastasis to the pineal region that were diagnosed in patients alive. Although occurring rarely, metastatic lesions should be considered in the differential diagnosis of pineal region tumors. PMID- 1890466 TI - Fetal head molding. Diagnosis by ultrasound and a review of the literature. AB - Head molding refers to changes in cranial bone relationships that occur in response to external compression force. In the normal term labor with vertex presentation, the suboccipito-bregmatic diameter shortens and the mentovertical diameter lengthens. This is accomplished partially through the unbending or straightening of the parietal bones rather than the frequently taught mechanism of overlapping sutures. The occipital and frontal bones may also contribute by an inward movement of their apex, using their basal portions as a hinge. A locking mechanism may occur in protracted labors as the free edges of the cranial bones are forced into one another, preventing further molding and providing more protection for the fetal brain. The preterm skull has weaker material properties and wider sutures. Thus, more molding at lower pressures is possible and the protective effect of "locking" may not be operational. A case of extreme antenatal preterm fetal head molding discovered at ultrasound is presented as an introduction to review the literature regarding molding. PMID- 1890467 TI - Symptomatic subarachnoid hemorrhage in the term newborn. AB - A review of the medical records of 35 term newborn infants with confirmed subarachnoid hemorrhage was undertaken to examine etiologic, clinical, laboratory, and neurodevelopmental aspects of this lesion. The most common clinical presentation was convulsive activity (69%), followed by apnea (23%), and bradycardia. Thirty-one of these infants (89%) survived, but only 16 (52%) were felt to be neurologically normal at latest evaluation. Outcomes appeared to be similar regardless of whether the presumed etiology was hypoxic-ischemic or traumatic. Six surviving infants (19%) developed post-hemorrhagic hydrocephalus, but in three of these there was a delayed presentation well beyond the neonatal period. Symptomatic subarachnoid hemorrhage in the term newborn may be a more serious event than previously believed. Close neurodevelopmental follow-up and surveillance for hydrocephalus is warranted. PMID- 1890468 TI - Free thyroxine levels in hospitalized newborns: depressed levels in critical, nonthyroidal illness. AB - Thyroxine and triiodothyronine levels are lower in preterm infants than in term infants. Until a distinction is made among hypothyroidism, prematurity, and illness as the cause, the necessity of treatment is unclear. Thyroxine, triiodothyronine, free thyroxine, and thyroid-stimulating hormone were measured weekly in 75 patients of 25 to 42 weeks gestational age. The range of thyroxine values among hospitalized term and preterm infants was lower than has been previously reported for healthy term newborns or infants. Thyroxine and triiodothyronine levels were consistently lower in preterm infants, but there were only minor differences between term and preterm infants' free thyroxine levels, which were both stable over time. Mean (SD) free thyroxine levels by week were 0.0259 (0.0079), 0.0259 (0.0057), 0.0201 (0.0066), 0.0274 (0.0079), 0.0241 (0.0023) nmol/L for term infants, and 0.0215 (0.0072), 0.0223 (0.0056), 0.0212 (0.0066), 0.0186 (0.0064), and 0.0201 (0.0021) nmol/L for preterm infants at weeks 1, 2, 3, 4, and greater than 4, respectively. Maturity was the best predictor of thyroxine or triiodothyronine levels, but illness was the clinical variable most highly correlated with free thyroxine. All 71 surviving infants were euthyroid at discharge. The free thyroxine measurement results suggest that hypothyroxinemia is not hypothyroidism but is a result of a combination of reduced protein-bound thyroxine as well as nonthyroidal illness. PMID- 1890469 TI - Massive vulvar edema complicating preeclampsia: a management dilemma. AB - We report two cases of massive antepartum vulvar edema in patients with preeclampsia. Medical therapy failed to relieve the edema. Both patients underwent cesarean deliveries because of fetal distress. Mechanical drainage of the edema fluid may be useful in women with this complication, however, if pregnancy termination is not urgent. PMID- 1890470 TI - Early-onset Hemophilus influenzae sepsis in the neonate. AB - Hemophilus influenzae sepsis has been increasingly reported in recent years. Thirteen neonates have been treated in our institution in the past 8 years, 12 of whom were admitted within the last 4 years. H influenzae is responsible for 8% of neonatal sepsis occurring during the first 3 days of life. It is usually transmitted before or at the time of birth and is more frequently encountered in premature and low birthweight infants. It is strongly associated with maternal obstetric complications particularly genitourinary tract infections and prolonged rupture of membranes before delivery. Most cases are caused by non-type-b strains and are susceptible to ampicillin. Neonatal H influenzae sepsis presents clinically like early-onset group B streptococcal disease and is especially fulminant in neonates born prematurely. PMID- 1890471 TI - The sensitivity and specificity of a preterm risk score for various patient populations. AB - Scoring systems to identify women at high risk for delivering low birthweight infants are used to place high-risk women into special prenatal clinics. The March of Dimes Birth Defects Foundation scoring system was evaluated to determine its sensitivity, specificity, and positive predictive value at each cutoff point between 0 and 20 for various patient profiles when conducted before 29 weeks' gestation. In the present study, 9014 singleton births in 1985 and 1986 from nine Florida county health units were reviewed. Scores of 1, 5, 10, and 20 provided a sensitivity of 0.96, 0.66, 0.26, and 0.02, a specificity of 0.05, 0.44, 0.86, and 0.99, and a positive predictive power of 8.7, 10.1, 15.9, and 21.1, respectively. Differences in the sensitivity and specificity of the scores existed among subsets in the study population classified by gravida, age, race, and urban or rural county. Overall, the applicability was restricted, and the positive predictive value appeared best if a cutoff point of 15 was used, which represented the upper 5th percentile of the population. It was concluded that a greater emphasis was needed to designate scores for specific subpopulations and to give more consideration to psychosocial factors associated with having low birthweight infants. PMID- 1890472 TI - A successful decade of regionalized perinatal care in Tennessee: the neonatal experience. AB - We hypothesized that successful implementation of regionalized perinatal care would result in early identification and antenatal referral of high-risk neonates, and also improved stabilization before and during transport of those transferred postnatally. We conducted a retrospective study of demographic characteristics and transport outcome in two defined groups of neonates transported to regional perinatal centers in Tennessee, one group (n = 218) from the first year of regionalization (1975), and a second group (n = 261) from the 12th year (1986). The percentage of outborn infants decreased, from 50% of all admissions in 1975 to 22% in 1986 (P = .005). Likewise, the percentage of low birthweight neonates transported after birth decreased, from 59% of all transports to 32% (P = .002). The frequency of stabilization measures performed before and during transport increased between study years (intravenous line placement: 12% to 58%, P = .0001; assisted ventilation: 10% to 33%, P = .001). The incidence of complications during transport decreased between study years (cyanosis: 25% to 8%, P = .0001; hypothermia: 30% to 3%, P = .0001; acidemia: 33% to 13%, P = .011). Both transport-related mortality and neonatal mortality decreased between study years (2.8% to 0.8%, P = .043; 17% to 7%, P = .0001, respectively). We conclude that regionalization during its first decade has been successful in improving perinatal care in Tennessee as indicated by favorable changes in referral patterns and improved outcome of transported neonates. PMID- 1890473 TI - Purpura fulminans in three cases of early-onset neonatal group B streptococcal meningitis. AB - The diagnosis of purpura fulminans was associated with three cases of early-onset group B beta-hemolytic streptococcal (GBS) disease. All three infants had confirmed bacterial disease, extensive purpuric lesions involving the extremities, and laboratory evidence of a consumptive coagulopathy. All three children survived but had markedly compromised neurologic outcomes. Purpura fulminans has not been previously reported with early-onset GBS disease. PMID- 1890474 TI - Blood pressure values in 500- to 750-gram birthweight infants in the first week of life. AB - The means and standard deviations for systolic, mean, and diastolic blood pressure were noted in the first week after delivery for 12 hemodynamically stable infants by a retrospective chart review. Blood pressure taken by means of an umbilical artery transducer or an oscillometer were not statistically different. All blood pressure values increased during the first week after birth. A trend was noted toward increasing blood pressure with increasing gestational age for the first week after birth. We conclude that the range of blood pressure in 500- to 750-g birthweight infants is extremely wide and that it may be necessary to use other clinical criteria in conjunction with blood pressure to determine which infants require intervention for hypotension. PMID- 1890475 TI - Predicting outcome of care in the neonatal intensive care unit. AB - The accuracy of a neonatal intensive care unit (NICU) staff in predicting the outcome and length of stay of infants admitted to the NICU, and the factors they felt were important in making these predictions, were evaluated. This prospective study used a questionnaire to survey 44 nurses, residents, and attending neonatologists working in the NICU about the predicted outcomes of 52 infants admitted to the NICU at the University of Nebraska Medical Center over a 1-month period. Factors previously identified by the staff as important indicators of infant outcome were assigned points of importance by the respondents, and specific values for these factors were recorded for each infant. The NICU staff indicated that gestational age was the most important indicator of infant outcome. The attending neonatologists placed more value on gestational age (analysis of variance [ANOVA] P less than .0001) than did the nurses or residents. Among the staff groups, there were significant differences in the weight or points assigned to a given factor for pulmonary function, renal function, number of resuscitations, and the "other" category (ANOVA P less than .05). The nurses ranked pulmonary function criteria lower than the residents did (P less than .04), but considered renal function more important than either the residents (P = .005) or the attending neonatologists considered it to be (P = .01). The number of resuscitations was ranked higher by the nursing staff than by other groups, whereas the attending neonatologists assigned less importance to the "other" category.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1890476 TI - Use of femur length measured by ultrasonography to predict fetal maturity. AB - The ultrasonographic criteria of biparietal diameter greater than or equal to 9.2 cm and a grade III placenta have been shown to correlate with fetal maturity in the fetus of a nondiabetic mother in our population. These two criteria have helped reduce the incidence of third-trimester amniocenteses by 66.6% at our institution. Occasionally, however, because of fetal position, we are unable to obtain an accurate biparietal diameter. We therefore carried out a prospective study of 120 patients to evaluate the relationship between femur length of greater than or equal to 7.3 cm and fetal maturity. In this study, the addition of the femur length criterion increased the specificity of the ultrasonographic criteria for fetal maturity from 66.6% to 85%. The data suggest that femur length could be used along with the biparietal diameter and placental grade as an alternative to amniocentesis in term nondiabetic pregnancies. PMID- 1890477 TI - Readjustment of hematocrit values after packed red cell transfusion in the neonate. AB - We studied the effect of packed red cell transfusion on the hematocrit values at 1 and 6 hours after transfusion in neonates. The mean hematocrits measured 1 and 6 hours following a 10 mL/kg transfusion were 40.0 +/- 4.38 and 40.4 +/- 4.40, respectively, in 11 transfusions given over a period of 3 hours. The mean hematocrits at 1 and 6 hours following a 10 mL/kg transfusion were 43.8 +/- 3.9 and 43.4 +/- 4.52, respectively, in 9 transfusions given over a period of 2 hours. The results in the study indicate that there was no significant difference in hematocrit observed between 1 and 6 hours following packed red cell transfusions given over a period of 2 or 3 hours. Therefore it is not necessary to wait for the customary 6 hours to determine the posttransfusion hematocrits, and the use of stored donor blood can be optimized for repeated blood transfusions. PMID- 1890478 TI - Managing the future: an examination of the neonatal intensive care unit. AB - The successes in neonatal intensive care have recently encountered the economic reality of the health care marketplace. Competition and cost constraints from new reimbursement formulas have affected the spirit of altruism that guided the early organization of perinatal regional care. Since high-risk neonatal care is so costly, it is more likely to be adversely affected by competition and cost containment than other inpatient services. The author proposes an examination of the concept of managed competition. Facing the reality of competition, the managers of neonatal units must strive to be cost competitive while maintaining quality of care. Hospitals with a disproportionate share of medically indigent patients must receive public support. To retain the concept of perinatal regional care, hospitals must form partnerships that assure appropriate high-risk care for the patient populations they serve. The public sector must monitor their arrangements to assure quality and access to the appropriate services by all patients in need of high-risk perinatal care. In this manner, the intent of the original perinatal regionalization concept can be preserved in an otherwise hostile competitive health care marketplace. PMID- 1890479 TI - Pain control after cesarean birth. Efficacy of patient-controlled analgesia vs traditional therapy (IM morphine). AB - A clinical trial compared the efficacy of a mechanical device to deliver patient controlled analgesia (PCA) (n = 25) with intramuscularly administered morphine (n = 17) for postcesarean pain management. Hypotheses were: (1) patient-controlled administration of narcotics will be superior (increased satisfaction, reduced pain, decreased sedation, increased ambulation, decreased length of stay), and (2) functional vital capacity will increase post-operatively with PCA. No differences in demographic variables were identified (P = less than or equal to .001). Differences in satisfaction (greater in PCA group, P = less than or equal to .05), ambulation (greater in PCA group, P = less than or equal to .001), amount of medication used (greater in PCA group, P = less than or equal to .001), and sedation level (less in PCA group, P = less than or equal to .05) were identified. No differences in vital capacity were identified. The hypothesis related to the superiority of PCA was accepted, while the association between PCA and increased vital capacity was not supported. The use of mechanical PCA devices provides an effective and safe means of managing postcesarean pain. PMID- 1890480 TI - Delayed cesarean section in preeclampsia with placental abruption and fetal distress. PMID- 1890481 TI - Neonatal radiology casebook. Umbilical artery catheter at level of patent ductus arteriosus. PMID- 1890482 TI - An interesting case presentation: pulmonary malformations associated with oculoauriculovertebral dysplasia (Goldenhar anomalad). AB - Oculoauriculovertebral dysplasia (OAV) is a heterogeneous field defect involving the first and second branchial arches and is characterized by microtia, mandibular hypoplasia, vertebral anomalies, and epibulbar dermoids. We report a case of OAV with pulmonary manifestations and review the literature regarding this association. Anomalies identified were previously undescribed tracheal stenosis, along with tracheoesophageal cleft and unilateral pulmonary agenesis. Recognition of the pulmonary malformations associated with OAV may lead clinicians to consider a diagnostic measure such as flexible fiberoptic endoscopy in the evaluation of infants with craniofacial malformations and respiratory distress. PMID- 1890483 TI - Access to care, Part 2. PMID- 1890484 TI - Acquired dyschromatopsia among styrene-exposed workers. AB - We investigated the occurrence of color vision loss in 75 styrene-exposed workers and in 60 referents. Color vision was evaluated by adopting the Lanthony D 15 desaturated panel, a test specifically suited to detect mild acquired dyschromatopsia. The results of the test were expressed as Color Confusion Index. Styrene exposure was evaluated with both environmental and biological monitoring. Airborne levels of the solvent were 3.2 to 549.5 mg/m3. In styrene-exposed workers color vision was significantly impaired when compared with referents matched for age. A significative correlation was found between environmental and urinary levels of styrene and Color Confusion Index excluding the influence of age in multiple regression analysis, indicating the possibility of a dose-effect relationship. The findings suggest that styrene can induce an early appearance of a dose-dependent color vision loss. PMID- 1890485 TI - Should helicopter frequent flyers wear head protection? A study of helmet effectiveness. AB - Flight helmets have been recommended as aircrew head protection since 1908, yet debate continues regarding their effectiveness. Estimates of helmet use in civilian helicopter aeromedical programs range from 6.5% to 13%. The effectiveness of the Army's SPH-4 flight helmet in reducing severe head injuries sustained during helicopter accidents was evaluated using the accident data base at the US Army Safety Center, Fort Rucker, Alabama. Analysis was restricted to severe (Class A) accidents that were at least partially survivable, using US Army Safety Center criteria. Occupants not wearing a protective helmet were significantly more likely to sustain severe and fatal head injuries than were occupants wearing the SPH-4 (RR = 3.8 and 6.3, respectively; P less than .01). Unhelmeted noncockpit occupants were at higher risk of head injuries (RR = 5.3 and 7.5; P less than .01). All personnel regularly participating in helicopter flight, civilian or military, should be equipped with protective headgear. PMID- 1890486 TI - A study of possible predictors of mesothelioma in shipyard workers exposed to asbestos. AB - In a prospective cohort study of 3893 shipyard workers, we estimated the value of medical monitoring, including chest radiograph, spirometry, and questions about smoking habits, asbestos exposure, and respiratory symptoms, as predictors of the risk of developing mesothelioma. There was no strong association between different exposure parameters and risk of mesothelioma. Impaired lung function and smoking were not predictors of risk of mesothelioma. Pleural plaque was not found to be associated with an increased risk of mesothelioma. Respiratory symptoms were of low value as predictors of risk of mesothelioma. Thus, traditional methods in health monitoring seem to be of low value in identifying persons with a high risk of mesothelioma in populations exposed to asbestos. PMID- 1890487 TI - Non-Hodgkin's lymphoma among Vietnam veterans. AB - In light of findings suggesting an increase in the risk for non-Hodgkin's lymphoma among men exposed to phenoxyherbicides and concerns among veterans over Agent Orange exposure, a hospital-based case-control study was undertaken to examine the association between military service in Vietnam and non-Hodgkin's lymphoma. The cases consisted of 201 Vietnam-era veteran patients who were treated in one of 172 Department of Veterans Affairs hospitals from 1969 through 1985 with a diagnosis of non-Hodgkin's lymphoma. 358 Vietnam-era veteran patients with a diagnosis other than malignant lymphoma served as a comparison group. Military service information was obtained from a review of the veteran's military personnel records. Service in Vietnam did not increase the risk of non-Hodgkin's lymphoma either in general (branch adjusted odds ratio = 1.03, 95% confidence interval = 0.70-1.50) or with increased latency period as defined as the duration in years from first service in Vietnam to hospital discharge. Surrogate measures of potential Agent Orange exposure such as service in a specific military branch, in a certain region within Vietnam, or in a combat role as determined by military occupational speciality were not associated with any increased risk of non Hodgkin's lymphoma. PMID- 1890488 TI - Mortality among Vietnam veterans: with methodological considerations. AB - The Department of Veterans Affairs previously conducted a proportionate mortality study of Army and Marine Vietnam-era veterans who died during 1965 through 1982. In the present study, 11,325 veterans who died during 1982 through 1984 and 50,743 veterans from the previous analysis made up the final sample of 62,068 veterans. When compared with all non-Vietnam veterans, Army Vietnam veterans had statistically significant excesses of deaths from external causes (proportionate mortality ratio [PMR] = 1.03), laryngeal cancer (PMR = 1.53), and lung cancer (PMR = 1.08). Marine Vietnam veterans had a significantly elevated PMR for external causes (PMR = 1.06) with a significant excess of homicide deaths (PMR = 1.16) when compared to all non-Vietnam veterans. The elevated PMRs for lung cancer and non-Hodgkin's lymphoma among Marine Vietnam veterans reported in the earlier VA study persisted when compared with Marine non-Vietnam veterans. However, it was found that these elevations probably were due to a deficit among the Marine non-Vietnam veterans rather than an excess among Marine Vietnam veterans. PMID- 1890490 TI - Computed tomography and high-resolution computed tomography of pneumoconioses. AB - The traditional imaging technique used in the assessment of patients suspected of having silicosis or asbestos-related disease has been the chest radiograph. However, computed tomography and high-resolution computed tomography have become widely available for these assessments. The relative merits of these techniques in the diagnosis of these diseases warrant review. PMID- 1890489 TI - Asbestosis: diagnostic dilution. AB - The term "asbestosis" usually has been applied to a disease characterized by diffuse pulmonary interstitial fibrosis. It was often associated with a significant adverse impact on the individual. A review of case definitions employed in published research studies show stability of the criteria for asbestosis case definitions over the past decade. Nevertheless, additional modalities have been suggested for the early diagnosis of asbestosis. It is probable that the significance of such abnormalities may be different from that of usual asbestosis, and there is therefore a need to carefully define the manner in which the terms are used. Additional anomalies may be seen in asbestos-exposed individuals including small airway physiologic abnormality, pathologic evidence of inflammation near the airways, positive gallium scan, abnormal lung compliance, exercise test abnormalities, CAT scan findings, and high-resolution CAT scan findings. PMID- 1890491 TI - Influence of high past lead-in-air exposures on the lead-in-blood levels of lead acid battery workers with continuing exposure. AB - We investigated the relationship between air lead levels and blood lead levels in 132 lead-acid battery workers in two plants who were followed for 30 months between 1983 and 1985 with frequent air lead and blood lead determinations. Both plants converted to more modern, expanded-metal battery manufacturing technologies around 1978 with associated reductions in mean air lead exposures from greater than 100 to less than 30 micrograms/m3. In multiple regression analyses including consideration of job category, seniority, age, ethnicity, gender, and smoking habit as covariates, there was a highly significant association of blood lead in micrograms/dL with air lead in micrograms/m3 (partial R2 = .20, P less than .0001) among the 68 workers in plant B but no association (P = .91) in plant A. Restriction of the regression analysis to those 44 workers in plant B with less than or equal to 22 years of seniority yielded the most significant air lead-blood lead association (partial R2 = .36, P less than .0001). Among the remaining 24 plant B workers, seniority, but not air lead, had a significant positive association with blood lead. Despite very stable air lead levels over the 30-month study, the 51 workers in plant A with more than 20 years' seniority had a mean decline of 0.04 microgram/dL in mean blood lead over the study period, whereas the 13 workers in plant A with less than or equal to 20 years' seniority had a mean increase of 7.6 microgram/dL.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1890492 TI - Medical surveillance for leukemia at a petrochemical manufacturing complex: four year summary. AB - Four-year results are presented on 2086 participants of a medical surveillance program of current and retired employees at a manufacturing complex in Illinois. Annual complete blood cell count testing and intensive follow-up of all out-of normal-range results began in 1985 on a voluntary basis. The program to date has not identified any evidence for an unusual distribution of out-of-range complete blood cell count results. Active employees with out-of-range complete blood cell count values had no increase in adverse health outcomes compared with those with in-range values. Retired employees with out-of-range values were more likely to have a serious underlying medical condition, but this appeared to be more a function of age than of occupational exposure. Four cases of myelodysplastic syndrome were brought to our attention as a result of the program, but there is no similarly followed population available for comparison to determine whether this represents an increase over expected cases. The lack of correlation of out of-range complete blood cell count results in active employees with serious hematologic disease raises significant questions about the utility of such surveillance for chemically exposed groups (eg, benzene-exposed workers) when exposure levels are low and well controlled. PMID- 1890493 TI - Disease clusters: a central and ongoing role in occupational health. AB - To review and evaluate whether the investigation of disease clusters continues to play an important role in establishing disease-toxin connections in the workplace, 87 original disease cluster reports were identified that established disease-toxin connections in occupational medicine (from 1775 to 1990). Four advantages of the workplace with regard to cluster discovery and investigation were identified: natural denominator boundaries, shared exposures, the ability to form intermediate hypotheses, and the possibility of locating comparable populations in which to study these hypotheses. Because new products, intermediate products, and procedures are introduced into working environments faster than epidemiologic and toxicologic studies can be designed to evaluate their potential risks, disease cluster investigations will remain central to the understanding of disease, and to protecting workers. PMID- 1890494 TI - Electrical contact and pregnancy. PMID- 1890495 TI - Psychiatric illness in patients with chronic fatigue and those with rheumatoid arthritis. AB - OBJECTIVES: To identify psychiatric differences between patients with chronic fatigue and those with rheumatoid arthritis and to investigate whether patients meeting Centers for Disease Control (CDC) criteria for chronic fatigue syndrome (CFS) can be differentiated from patients with chronic fatigue on measures of disability and psychosocial distress. DESIGN: Cross-sectional study comparing 98 patients with chronic fatigue with 31 patients with rheumatoid arthritis on structured psychiatric interviews and patient questionnaires. Nineteen patients meeting CDC criteria for CFS were compared with 79 patients with chronic fatigue not meeting CDC criteria on questionnaires measuring disability and psychosocial distress. SETTING: Consecutive patients with chronic fatigue were selected from a chronic fatigue clinic at the University of Washington, and 31 consecutive patients with rheumatoid arthritis were sampled from a private rheumatology practice. MAIN RESULTS: Patients with chronic fatigue had a significantly higher prevalence of lifetime major depression and somatization disorder than did patients with rheumatoid arthritis. Patients with chronic fatigue also had a significantly higher prevalence of current and lifetime psychiatric diagnoses. Only 19 of 98 patients with chronic fatigue met CDC criteria for CFS. Patients meeting CDC criteria for CFS could not be differentiated from the larger group of patients with chronic fatigue on any study variable. CONCLUSIONS: Patients with chronic fatigue have a significantly higher burden of psychiatric illness than do patients with rheumatoid arthritis. The psychiatric illness preceded the development of chronic fatigue in over half the patients. Centers for Disease Control criteria for CFS did not select a subset of chronic fatigue patients who could be differentiated on disability or psychosocial parameters from patients with chronic fatigue who did not meet CDC criteria. PMID- 1890496 TI - HIV-positive women: reasons they are tested for HIV and their clinical characteristics on entry into the health care system. AB - STUDY OBJECTIVE: To describe the reasons for the HIV testing of HIV-positive women and their clinical presentation and to make specific laboratory comparisons between women intravenous drug users (IVDUs) and non-IVDUs who were heterosexually infected (HTs). DESIGN: Consecutive case series. SETTING: Four primary care sites associated with the Brown University AIDS Program. PARTICIPANTS: 140 consecutive HIV-seropositive women. RESULTS: The most common reason for HIV testing in both groups was self-perception of risk. Presenting T helper lymphocyte counts, leukocyte counts, and hematocrits did not differ significantly between the groups. Intravenous drug users were significantly more likely than HTs to have evidence of hepatitis B virus exposure (p less than 0.0001) and to report the history of a sexually transmitted disease (p = 0.005). Twenty percent of HTs versus 10% of IVDUs were tested only after they had HIV related symptoms. The most frequent clinical presentation for both groups was Centers for Disease Control Group IV/A constitutional symptoms. CONCLUSIONS: Many HIV-seropositive women do not enter the health care system until they are symptomatic, but those infected heterosexually and those using parenteral drugs have similar laboratory indices at presentation. AIDS education strategies toward all women at risk must include information about manifestations of HIV disease in women, as well as preventive measures, to ensure early access to the health care system. PMID- 1890497 TI - Sexual function of women taking antihypertensive agents: a comparative study. AB - OBJECTIVE: To develop a method to evaluate the effects of clonidine and prazosin on sexual function in hypertensive women. DESIGN: Crossover, active-drug controlled pilot study. SETTING: Community recruitment to a university-based teaching hospital. PATIENTS: Ten premenopausal and eight postmenopausal women with mild hypertension and unimpaired sexual function. INTERVENTION: Periodic, self-administered daily diaries assessed the sexual arousal and desire and orgasmic function of women receiving placebo, clonidine, and prazosin. MEASUREMENTS AND MAIN RESULTS: Using analysis of variance for orgasmic characteristics and comparison of the percentages of yes responses to the sexual function questions, no significant difference in the levels of sexual function of women receiving placebo, clonidine, and prazosin was found. However, there was a suggestion that clonidine and prazosin affected some aspects of sexual function. Of the women who received clonidine first, fewer were receptive to partner approach during medication therapy (49%) than during placebo (61%). Fewer women wished for their partners to approach them (WISH) during therapy (41% and 53% for clonidine and prazosin, respectively) than during placebo (60%). In the group that received prazosin first, WISH was affected (32% for prazosin, 31% for clonidine, 45% for placebo). Orgasmic strength increased from 2.1 on placebo to 2.7 on clonidine (second medication), measured on a four-point Likert scale. CONCLUSIONS: This pilot study developed a method using self-administered daily diaries for evaluating the effects of antihypertensive agents on sexual function in hypertensive women. These potential effects need to be evaluated in larger studies. PMID- 1890498 TI - A survey of alcohol use in an inner-city ambulatory care setting. AB - OBJECTIVE: To measure the prevalence of current drinking and potential problem drinking in an inner-city ambulatory care setting, using the CAGE questionnaire. DESIGN: Survey of patients attending ambulatory care clinics, using structured personal interviews. SETTING: Three ambulatory care clinics serving an indigent, predominantly black population of metropolitan Atlanta: a general medical appointment clinic, a walk-in clinic, and a neighborhood primary care clinic. PATIENTS/PARTICIPANTS: Patients over the age of 18 who attended one of the above clinics on a day when interviewers were available and who were estimated to have more than a 45-minute wait prior to seeing their health provider. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: 15.3% of subjects had CAGE scores greater than or equal to 2 (95% CI 12.2, 19.0). A CAGE score of greater than or equal to 2 was almost three times more common in men than in women, 26.7% vs. 9.5%. Only 8.6% (95% CI 6.3, 11.7) of subjects reported drinking greater than or equal to 2 drinks per day. These findings suggest that problem drinking may affect as many as one in six people seeking care in inner-city ambulatory care clinics and provide support for the use of screening instruments such as the CAGE questionnaire for improved sensitivity in detecting alcoholism in these practice settings. PMID- 1890499 TI - A prospective study of the effects of cigarette smoking and alcohol abuse on mortality. AB - OBJECTIVE: To compare the relative risks of alcohol abuse and cigarette smoking. DESIGN: Cohort studies utilizing a 12-to-16-year follow-up of 47-to-52-year old men. PARTICIPANTS AND SETTING: 237 Caucasian college sophomores (COLLEGE sample) and 366 socially disadvantaged junior high school students (CORE-CITY sample) selected in 1940-43 for relative mental health and for interdisciplinary study. MAIN RESULTS: The presence of many risk factors for death, including alcohol abuse and smoking, had been assessed prior to age 47 (CORE-CITY sample) and age 52 (COLLEGE sample). Over the next 12 years (CORE-CITY sample) and the next 16 years (COLLEGE sample), the men's mortality was monitored. Heavy use of cigarettes and alcohol abuse were highly correlated. When the effect of alcohol abuse was controlled, heavy smoking was associated with elevated mortality risks in both samples, although this was not statistically significant in the CORE-CITY sample. When smoking was controlled, the odds ratios for mortality from alcohol abuse were substantial in both samples. CONCLUSIONS: These results and a literature review suggest that insufficient alcohol abuse histories may lead clinicians to underestimate the mortality risk of alcohol abuse. PMID- 1890500 TI - Smoking cessation following admission to a coronary care unit. AB - OBJECTIVE: To determine the impact of an episode of serious cardiovascular disease on smoking behavior and to identify factors associated with smoking cessation in this setting. DESIGN: Prospective observational study in which smokers admitted to a coronary care unit (CCU) were followed for one year after hospital discharge to determine subsequent smoking behavior. SETTING: Coronary care unit of a teaching hospital. PATIENTS: Preadmission smoking status was assessed in all 828 patients admitted to the CCU during one year. The 310 smokers surviving to hospital discharge were followed and their smoking behaviors assessed by self-report at six and 12 months. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Six months after discharge, 32% of survivors were not smoking; the rate of sustained cessation at one year was 25%. Smokers with a new diagnosis of coronary heart disease (CHD) made during hospitalization had the highest cessation rate (53% vs. 31%, p = 0.01). On multivariate analysis, smoking cessation was more likely if patients were discharged with a diagnosis of CHD, had no prior history of CHD, were lighter smokers (less than 1 pack/day), and had congestive heart failure during hospitalization. Among smokers admitted because of suspected myocardial infarction (MI), cessation was more likely if the diagnosis was CHD than if it was noncoronary (37% vs. 19%, p less than 0.05), but a diagnosis of MI led to no more smoking cessation than did coronary insufficiency. CONCLUSION: Hospitalization in a CCU is a stimulus to long-term smoking cessation, especially for lighter smokers and those with a new diagnosis of CHD. Admission to a CCU may represent a time when smoking habits are particularly susceptible to intervention. Smoking cessation in this setting should improve patient outcomes because cessation reduces cardiovascular mortality, even when quitting occurs after the onset of CHD. PMID- 1890501 TI - Social and clinical features as predictors of outcome in outpatient alcohol withdrawal. AB - OBJECTIVE: To identify patient features--both social and clinical--that may be associated with treatment failure in outpatient alcohol withdrawal. DESIGN: A prospective observational cohort study of patients who underwent outpatient management of the alcohol withdrawal syndrome. SETTING: Community hospital-based outpatient alcohol treatment program. PATIENTS: The 179 patients who were eligible for and participated in a clinical trial of drug therapy for outpatient management of the alcohol withdrawal syndrome. MAIN RESULTS: Treatment failure occurred for 45% (80/179) of the patients. Failure rating did not vary according to diverse sociodemographic features such as age, level of education, income, medical insurance status, and marital status. Persons who were homeless did as well as those who were not. In contrast, two clinical features of withdrawal were associated with significantly higher rates of treatment failure: craving and withdrawal symptom severity. High cravers had a treatment failure rate of 56% (22/39), compared with 36% (41/115) for those with lower scores (p less than 0.03). Among those with moderate-to-high withdrawal symptom severity, 49% (74/151) represented treatment failures, compared with 22% (6/27) of those in the low-symptom group (p less than 0.01). CONCLUSIONS: While these data do not confirm that socially disadvantaged persons are at increased risk for withdrawal treatment failure, two clinical features--craving and withdrawal symptom severity -may help identify high-risk patients. PMID- 1890503 TI - Physicians' attitudes towards living wills and cardiopulmonary resuscitation. AB - OBJECTIVE: To determine whether a physician's familiarity with the living will directly relates to an expressed willingness to discuss resuscitation issues with patients. DESIGN: Survey of selected primary care and medical sub-specialist physicians most likely to care for seriously or terminally ill patients. SETTING: Private-practice clinicians practicing in an urban county. PARTICIPANTS: Internists, family practitioners, cardiologists, oncologists, and neurologists in private practice. INTERVENTIONS: None. RESULTS: Almost all responding physicians (97.2%) knew of the living will, although few (13.5%) had executed one for themselves. Most were willing to keep a copy of their patients' living wills with their office records. However, only a few physicians (20%) indicated they routinely discussed extraordinary care issues with their patients. In fact, most (70%) reported they rarely or never discussed cardiopulmonary resuscitation (CPR) with their patients. With terminally ill patients, physician initiative was greater: 69% reported discussing resuscitation preferences. Comparable discussions with elderly patients were undertaken only if the physician believed they would be warranted by the clinical circumstances. When questioned about their own sentiments towards resuscitation, most physicians indicated they would not want CPR if they were terminally ill (86%) or mentally incompetent (93%). A similar number (92%) would refuse artificial feeding if permanently comatose. CONCLUSIONS: Many physicians recognize the importance of living wills as an expression of patient treatment preferences. Nevertheless, discussion of patient preferences is unlikely because of physicians' reluctance, except in limited circumstances, to initiate a dialogue about life-sustaining measures. Because patients also are often unwilling to begin such discussions, better methods of facilitating discussion of CPR and other extraordinary health care measures must be sought. PMID- 1890502 TI - Prevalence of domestic violence among patients in three ambulatory care internal medicine clinics. AB - OBJECTIVE: To determine the prevalence of domestic violence among patients seen in three university-affiliated ambulatory care internal medicine clinics and to assess the personal characteristics of those patients affected by domestic violence. DESIGN: Survey using a self-administered, anonymous questionnaire. SETTING: Three university-affiliated internal medicine clinics at the University of California Irvine Medical Center. PARTICIPANTS: We asked all patients on randomly selected days during the three-month study to participate. 453 (72%) of the 629 eligible English- and Spanish-speaking patients completed the questionnaire. MEASUREMENTS AND MAIN RESULTS: 28% of participants had experienced domestic violence at some time in their lives, and 14% were currently experiencing domestic violence. Logistic regression analysis showed that female gender, unmarried status, and poverty were important predictors of domestic violence. However, domestic violence occurred in all groups regardless of sex, ethnicity, age, or socioeconomic status. CONCLUSIONS: The study found an unexpectedly high prevalence of domestic violence in the three internal medicine clinics. Physicians should ask their patients routinely about domestic violence and, when domestic violence is present, should offer emotional support, information about social service agencies, and psychological care. PMID- 1890504 TI - Affecting residents' literature reading attitudes, behaviors, and knowledge through a journal club intervention. AB - OBJECTIVE: To investigate whether a limited teaching intervention, based on principles of adult education, could change residents' literature reading attitudes, behaviors, and knowledge. DESIGN: The educational intervention supplemented an ongoing bimonthly journal club. The effects on residents were studied prospectively before and four months following the intervention. SETTING: A community hospital internal medicine training program. PARTICIPANTS: All 14 residents: six in the first year, and four each in the second and third years of training. INTERVENTION: A one-hour seminar incorporating principles of adult education, including the use of multiple teaching modalities. The content was based on the critical literature reading guidelines published by the McMaster group. Reinforcement of learning objectives was achieved by learner participation, written assignments, active feedback, and follow-up in subsequent journal clubs. RESULTS: Residents improved their performances on objective testing of critical appraisal knowledge by 60% (p = 0.02). They reported improved ability to appraise original research articles critically (p = 0.01) and reported spending more useful time reading. Unaffected were the total time spent reading journals, the reasons for reading them, and the perceived value of journals in "keeping up" with advances in medical knowledge. CONCLUSION: Journal clubs are important to residents, and their effectiveness in teaching critical appraisal and promoting reading of the literature may be augmented by applying principles of adult education. PMID- 1890506 TI - Blueprint for a research career in general internal medicine. AB - An academic career in general internal medicine is a challenging but rewarding endeavor. The strategies for success require flexibility as the ground rules may change. Nevertheless, attention to the aforementioned principles will help the academic generalist to swim with sharks and survive, and simultaneously to promote the entire field of academic general internal medicine. PMID- 1890505 TI - Factors associated with the frequency of house calls by primary care physicians. AB - OBJECTIVE: To evaluate factors associated with the frequency of house calls by primary care physicians. DESIGN: A cross-sectional design with a self administered mailed survey. SITTING/PARTICIPANTS: 751 primary care physicians who care for Medicaid patients in Virginia. RESULTS: Among 389 physician respondents (52%), regular house callers (n = 216) were compared with occasional house callers (n = 162). Among physician characteristics, specialty and practice duration were associated with house call frequency. Regular house callers also more often cited chronic illness (67% vs. 20%, p less than 0.01) and terminal illness (67% vs. 40%, p less than 0.01) as indications for house calls, compared with occasional house callers. Use of visiting nurses to substitute for physician house calls was less often considered appropriate by frequent house callers (7% vs. 24%, p less than 0.01), and regular house callers were less likely to report being "too busy" to make house calls (71% vs. 29%, p less than 0.01). Multivariate analysis confirmed the association of these attitudes with house call frequency. CONCLUSION: These data suggest that specific attitudes among primary care physicians are associated with house call frequency. PMID- 1890507 TI - Our hands are tied: legally induced moral tensions in health care delivery. PMID- 1890508 TI - Medical informatics in postgraduate training: a way to improve office-based practitioner information management. AB - Medical informatics has the potential to revolutionize patient care by providing every physician with rapid, easy access to the entire medical knowledge base. However, many changes are needed in the way systems are designed and physicians are trained before this potential can be realized. It is the shared responsibility of the medical informatics community, professional societies, academic organizations, and practitioners to accept the challenge of turning the power and promise of modern computer technology into useful tools for the care of patients. PMID- 1890509 TI - The challenging case conference: an integrated approach to resident education and support. PMID- 1890510 TI - Abdominal aortic aneurysm. PMID- 1890512 TI - HIV infection in women: diverse approaches to a growing problem. PMID- 1890513 TI - Costs of antihypertensive therapy. PMID- 1890514 TI - Elimination of the patient's race from the case presentation. PMID- 1890511 TI - Adverse neurologic effects of glucocorticosteroids. PMID- 1890515 TI - Eating disorders and substance abuse in men. PMID- 1890516 TI - Computerized digital enhancement in craniofacial cephalometric radiography. AB - Application of digital radiologic imaging techniques to cephalometric assessment of the craniofacial skeleton is presented. Digital-enhanced and standard cephalometric radiographs were compared by osseous and soft tissue landmark analysis. Although both radiographic methods exhibited comparable accuracy at identifying bony landmarks, digital enhancement was consistently superior at delineating soft tissue relationships. PMID- 1890517 TI - Rectal ketamine and midazolam for premedication in pediatric dentistry. AB - Rectally administered midazolam (0.30 mg/kg) and ketamine (5 mg/kg) were compared for preanesthetic medication in children undergoing dental extractions. Sixty patients between the ages 2 and 9 years were randomly allocated to three groups in this double-blind study. In one group of patients who received ketamine rectally, intravenous midazolam (0.05 mg/kg) also was administered immediately after induction of anesthesia. The results from this trial show that 30 minutes after rectal administration of the two drugs, good anxiolysis, sedation, and cooperation were obtained in most patients. Although midazolam appeared to be marginally more efficacious than ketamine in the majority of assessments made and seemed to have less adverse effects, no statistically significant differences could be shown. Ketamine showed a slight decrease and midazolam a slight increase in average blood pressures after premedication. These blood pressure differences were, however, considered to be of little clinical importance. PMID- 1890519 TI - Postoperative computed tomography study of pterygomaxillary separation during the Le Fort I osteotomy. AB - Computed tomography (CT) was used postoperatively to assess the pterygomaxillary region in 12 orthognathic surgery patients who had had a Le Fort I osteotomy. Although pterygomaxillary separation was successful in all cases, in only 41.6% of the sides did fractures of the plate not occur. The incidence of low pterygoid plate fracture was 37.5% and that of high pterygoid plate fracture was 25%; 4.2% of sides showed a maxillary tuberosity fracture. Multiple fractures were observed in 8.3% of separated plates. Of 17 pterygoid plates judged clinically to be intact, only 10 were intact as assessed by CT. The significance of these findings and application of CT to evaluation of modifications to the Le Fort I osteotomy is discussed. PMID- 1890518 TI - Analysis of reconstruction for anterior mandibular defects using AO plates. AB - The functional and cosmetic outcome of 11 patients who had anterior arch mandibulectomy for stage II-IV oral cavity carcinoma and were reconstructed with AO stainless-steel or titanium plates was retrospectively analyzed. Although the complication rate was high, plate removal was uncommon. Patients were afforded good function and cosmesis. Severity of postoperative infection corresponded to a low preoperative absolute lymphocyte count, which suggests that increased preoperative diet supplementation may decrease the incidence of early infections. Improved mandibular function and esthetics may allow future patients to be offered early reconstruction routinely. PMID- 1890520 TI - Does prestretching stainless-steel wire have any clinical significance? AB - Clinical parameters of prestretch and tension forces placed on stainless-steel wire by 20 oral and maxillofacial surgeons were obtained. Unstretched wire was clinically as tough or tougher than prestretched wire of a similar gauge. Both prestretched and unstretched wires, twisted to their maximum, loosened when under tension. As the prestretch forces increased, the clinical strength of the wire diminished. PMID- 1890521 TI - Tissue responses to degenerative changes in the temporomandibular joint: a review. AB - The articular cartilage covering of the mandibular condyle and the articular eminence, as well as the tissue of the articular disc, may be affected by degenerative changes associated with osteoarthrosis. Degenerative changes of cartilage alter its physical properties and, as a result, affect its ability to withstand compressive and shearing stresses. Increased friction between the articular surfaces may impair joint movement and may elicit compensatory or pathologic responses of the cartilage and the adjacent tissues, such as capsule and ligaments, synovial membrane, subchondral bone, and associated musculature. In this review, these structural changes are described and related to common signs and symptoms of craniomandibular dysfunction, such as clicking, locking and instability, pain and tenderness, restricted ranges of mandibular motion, crepitation, deformity, muscle wasting, and changes of occlusion. PMID- 1890522 TI - Modified Le Fort I (maxillary-zygomatic) osteotomy: rationale, basis, and surgical technique. AB - A modified version of the Le Fort I maxillary osteotomy is described. The esthetic and anatomic basis, the surgical technique, and possible complications are discussed and two representative cases are shown. This technique has been used to treat 38 patients with various degrees of combined maxillary-zygomatic deficiency in the last 3 years. Based on this experience, it is concluded that this procedure provides a predictable esthetic result and excellent skeletal stability with few intraoperative and postoperative complications. Furthermore, the need for simultaneous bone grafting or alloplastic implants, as in the conventional Le Fort I, is virtually eliminated using this osteotomy. PMID- 1890523 TI - Bridging of mandibular defects with two different reconstruction systems: an experimental study. AB - To compare two different mandibular reconstruction systems, a 5-cm angular resection was performed in nine adult sheep. The defect was reconstructed using either a classic AO plate or the AO-THORP reconstruction system. The animals were killed 5, 9, and 14 weeks after operation. Serial sections with the plates and screws in place were prepared and studied histologically and with microradiography and fluorescence microscopy. Twenty-six percent of the 2.7-mm AO cortical screws were adequately fixed. The corresponding percentage for AO-THORP hollow screws was 73%. The main advantage of the latter system is the screw-plate locking principle, which allows plate stability to be maintained even if bone is resorbed under the plate. Whether the existence of a screw lumen is an advantage has not yet been established. PMID- 1890524 TI - Facial erysipelas: report of a case and review of the literature. AB - The diagnosis of erysipelas is usually made clinically. Features that help distinguish erysipelas are acute onset, erythema, warmth, edema, pain, fever, and isolated regional involvement with clearly demarcated margins. High ASO titers and response to penicillin therapy are reassuring. Simple uncomplicated erysipelas or cellulitis in adults can usually be treated on an outpatient basis. Extensive facial involvement with fever and a toxic appearance warrants hospitalization. Facial cellulitis or erysipelas in children, unless quite limited, requires hospitalization because of the high risk of Hemophilus influenzae infection and sepsis. Hospitalized patients should show visible signs of resolution and be afebrile for at least 24 hours prior to discharge. They should be maintained on oral antibiotic therapy at home for an additional 7 to 10 days. PMID- 1890525 TI - Metastatic retinoblastoma to the orofacial region. PMID- 1890526 TI - Neuroblastoma metastatic to the mandible. PMID- 1890527 TI - Benign angiofollicular lymph node hyperplasia (Castleman's disease) presenting as a solitary cervical mass. PMID- 1890528 TI - Bone screws as an aid in vestibuloplasty procedures. PMID- 1890529 TI - The importance of imaging in TMJ surgery. PMID- 1890530 TI - Chewing and swallowing activity of masticatory muscles in patients with a complete upper and a partial lower denture. AB - The chewing and swallowing activity of jaw-closing muscles was studied longitudinally in 30 partially edentulous subjects who were provided with an immediate complete upper and a partial lower denture. Electromyographic recordings of the anterior temporal and masseter muscles were obtained during habitual chewing of apple and during swallowing of saliva and water, before final extractions and 7 weeks, 6 months, 1 year and 2 years after denture insertion. At the pre-treatment stage, when the patients were chewing with a residual anterior dentition, the mean voltages showed low values compared to findings reported in subjects with a complete natural dentition. After 6 months of denture use, the chewing forces showed significant increases in amplitude, and the increased force of contraction persisted to the 2-year stage. The recordings of swallowing revealed no significant changes in maximal mean voltage during the observation period. However, there was a significant increase in the duration of the swallows after 1 year of denture wearing, which might be related to stabilization of the complete upper denture due to continuing resorption of the maxillary ridge. PMID- 1890531 TI - Causes and signs of temporomandibular joint pain and dysfunction: an electromyographical investigation. AB - The spontaneous muscular activity of the masseter and two non-masticatory muscles, and their activity under conditions of noise and flickering light, were recorded in 30 patients with mandibular dysfunction, and in 25 control subjects. The mood of the subjects during the investigation, and the possible presence of emotional disturbances was evaluated by means of questionnaires. The enhanced muscular activity of the masseter muscle differentiated patients from the control group, although it does not constitute a pathognomic sign. Unilaterality of complaints, and dysfunctions of differing intensity were not reflected in differential EMG findings. One-fifth of the patients exhibited neck muscle activity occurring simultaneously with the masseter activity. The effect of the applied stimuli on the muscular activity was not homogeneous, leading to activation in some cases and inhibition in others. Symptoms of anxiety could be observed in seven TMJ patients. Anxious patients showed higher levels of muscular activity and emotional irritability during the experiment than non-anxious patients. PMID- 1890532 TI - Effectiveness of fortnightly tooth brushing with amine fluorides in caries-prone subjects. AB - The aim of this study was to assess the caries incidence and plaque accumulation in schoolchildren at caries risk, after brushing the teeth fortnightly with gels containing 0, 0.4% F, 1.25% F as amine fluoride (AmF) or the common amine fluoride toothpaste containing 0.125% F. The study was conducted double blind over an 18-month period, and after 6 months discontinuation of brushing. Only the group that brushed with the 1.25% AmF gel showed a significant decrease in caries development compared to the group that brushed with the 0.125% AmF toothpaste. During the 6-month discontinuation period, the incidence of caries increased in all groups; the differences in caries development between all groups were not significant. Plaque indices were significantly lower in the AmF-treated groups. The highest fluoride concentration in the gel reduced the development of caries to zero, probably due to increased fluoride levels in the oral milieu of caries risk children. In order to maintain a positive effect of fluoride over an extended time period, caries-prone subjects should continue an initiated fluoride programme. PMID- 1890533 TI - Functional stress modification after high condylectomy surgery. AB - Surgical removal of the head of the condyles inevitably leads to radical redistribution of loads applied to the mandible. The nature of this redistribution can have important implications on the surgical approach and subsequent reconstructive procedures. The purpose of this investigation was to visualize photoelastically the functionally delivered stresses after high condylectomy surgery. Three identical models of a dentate human mandible were constructed from a photoelastic material. One mandible simulated a unilateral and the other simulated a bilateral high condylectomy. The third mandible had both condyles intact and served as basis for comparisons. Silicone implants were placed on the sectioned condylar heads. The condyles, with the silicone implants, were fitted into simulated fossae and the mandibles were loaded unilaterally and bilaterally. The resulting stresses were observed and photographed in the field of a circular polariscope. Substantial differences in load-generated stresses were observed as a result of both unilateral and bilateral condylectomies, compared to the normal case. The most severe stress conditions occurred with the unilateral condylectomy, where stresses associated with torsion were most evident. PMID- 1890534 TI - The masseteric reflex evoked by tooth and denture tapping. AB - The characteristics of the masseter reflex evoked by tapping a maxillary incisor were compared with the reflex pattern evoked by tapping a corresponding denture tooth after insertion of an immediate denture. Up to three inhibitory phases (I 1, I-2 and I-3), followed by excitation, were found on an averaged EMG. The tapping force threshold for the early inhibitory phase was lower than for the late phases. The pattern of the reflex was generally the same before and after insertion of the denture, but the threshold values increased. After insertion of the denture, the threshold for I-1 increased from 1 +/- 0.3N to 2.2 +/- 0.4N, the threshold for I-2 increased from 2.4 +/- 0.8N to 3.8 +/- 0.9N, and the threshold for I-3 increased from 5.1 +/- 0.6N to 8.3 +/- 0.9N. The latency period for I-1 also increased from 12.3 +/- 0.5 ms to 13.1 +/- 0.3 ms after insertion of the denture. After relining, the threshold for evoking I-1 decreased from 2.7 +/- 1.2N to 1.2 +/- 0.6N. It was assumed that the mechanoreceptors situated in the mucosa under the denture base could take over the functional role of the periodontal mechanoreceptors for evoking the masseter reflex during tapping, and that these afferents probably had connections to the same interneurones. PMID- 1890535 TI - Comparison of amalgam behaviour under static and cyclic sub-modulus of rupture loading. AB - The behaviour of amalgam beam specimens subjected to a sub-modulus of rupture load at 37 degrees C was compared in static and cyclic modes. Testing was performed using identical equipment, with cyclic testing conducted by intermittent load application for both tests. The specimens tested exhibited varying degrees of deformation and times to fracture in both tests. The mode of load application, either cyclic or static, did not appear to have a significant effect on the degree of amalgam deformation or time to fracture. The most important factors relating to deformation are time of total load application, creep of the specific amalgam and temperature of testing. PMID- 1890536 TI - Magnesium sulphate as a new desensitizing agent. AB - Various desensitizing agents have been used in clinics to solve the problem of dentinal hypersensitivity (DH), but none of them has been shown to be consistently effective. We here introduce a new type of desensitizing agent, i.e. 4% magnesium sulphate with iontophoresis at 2mA for 3 min. These optimal conditions were determined by animal experiments, while only a minor effect on dentinal issues was observed within 4 weeks after the treatment. When this desensitizing agent was used to treat DH, the cure rate of 62.4% remained steady within the 25-week observation period, while some effect was achieved in all the subjects who participated in the study. PMID- 1890537 TI - Measurement of human ventricular myosin light chain-1 by monoclonal solid-phase enzyme immunoassay in patients with acute myocardial infarction. AB - A monoclonal solid-phase enzyme immunoassay has been developed for the detection of human serum ventricular myosin light chain-1. Cross-reactivity of this with human skeletal muscle myosin was observed, but the enzyme immunoassay with the sera of patients with acute myocardial infarction gave similar results with radioimmunoassay. The human ventricular myosin light chain-1 levels in the healthy subjects were 0.2-6.6 ng/ml in males and 0.2-4.1 ng/ml in females. Within run and between-run precision (CVs) of the assays was on the order of 2.3-4.7% and 4.3-8.7, respectively. Sensitivity of the assay was 1.0 ng/ml, and working range was 5-100 ng/ml. In all patients with define acute myocardial infarction, serum ventricular myosin light chain-1 levels increased three- to ten-fold the upper reference range within 6 hr after the onset of chest pains. Two types of subtrend were discovered: its levels remain elevated for 3-4 days and its levels increased and then decreased 1-2 days after the initial rise but became elevated again for the next 4-7 days after the onset of chest pain, which is in contrast to the case with all conventionally used biochemical cardiac markers. PMID- 1890538 TI - Evaluation of serum sialic acid and carcinoembryonic antigen for the detection of early-stage colorectal cancer. AB - Various expressions of elevated serum sialic acid (total sialic acid, TSA: lipid associated sialic acid, LASA; LASA/TSA; TSA normalized to total protein, TSA/TP) have been evaluated and compared with increased serum carcinoembryonic antigen (CEA) levels for the detection of early-stage colorectal cancer. This evaluation was done blindly on a coded panel of 320 sera from staged colorectal cancer patients and controls provided by the Mayo Clinic--National Cancer Institute Diagnostic Bank. Unlike the findings of a previous preliminary study (Tautu et al., JNCI 80:1333-1337, 1988), the ratio of LASA/TSA was not useful for detecting early-stage (Dukes A and B) colorectal cancer. However, TSA and TSA/TP values were significantly elevated in each colorectal cancer subgroup compared with normal controls. TSA and TSA/TP values displayed a marginally better discriminatory power than CEA values in the case of Dukes A subgroup with respect to normal controls. CEA still appears to be the best single overall marker for discriminating between colorectal cancers and controls. However, multiple marker analysis using CEA and TSA (and related markers) appears to be more sensitive than CEA alone for detecting colorectal cancer. PMID- 1890539 TI - Cryopreservation and long-term liquid nitrogen storage of peripheral blood mononuclear cells for flow cytometry analysis: effects on cell subset proportions and fluorescence intensity. AB - The effect of cryopreservation and long-term liquid nitrogen storage on peripheral blood mononuclear cell (PBMC) subsets was prospectively analyzed using monoclonal antibodies and flow cytometry. Brief cryopreservation did not significantly alter the proportion of positively stained cells for CD3+, CD4+, CD8+, CD14+, CD16+, and CD19+ cells. A small but statistically significant increase in the proportion of positive cells was observed for HLA-DR+ and HLe-1+ cells. Brief cryopreservation was associated with a decrease in the mean fluorescence intensity (MFI) values for CD3+, CD4+, and CD8+ cells; an increase in MFI values for CD14+ and HLA-DR+ cells; and no change for CD16+, CD19+, and HLe-1+ cells. There was no significant change in the proportion of CD3+, CD4+, or CD16+ cells during 20 months of storage in liquid nitrogen. Small but statistically significant decreases in the proportion of CD8+ and CD19+ cells were observed over the same interval, and the proportion of CD14+ cells (monocytes) was highly variable. Chronologic changes in fluorescence intensity during long-term storage were observed for all cell subsets except CD16+ and CD19+ cells. Cryopreservation is a valuable technique for long-term storage of viable cells. For many laboratory applications, the small changes noted in the present study will have no practical importance. However, for clinical and epidemiological investigations encompassing large numbers of samples, statistical techniques to adjust for small changes during storage should be considered. PMID- 1890540 TI - Relative quantification of collagen mRNA in fibroblasts by a radioactive polymerase chain reaction technique. AB - A radioactive polymerase chain reaction (PCR) method has been developed for the relative quantification of the human alpha-2 chain of type I collagen [hu alpha 2(I)] in cells. cDNAs generated by reverse transcription from the total pool of cytoplasmic RNA serve as a template for polymerase chain reaction amplification of a hu alpha-2(I) cDNA primed by two sequence-specific synthetic oligonucleotides. The distinctive 390 bp hu alpha-2(I) cDNA and two Aval fragments of 220 and 170 bp are identified by agarose gel electrophoresis. alpha 32P-dCTP of defined specific activity is included in the PCR reaction and the 390 bp cDNA is excised from the electrophoresis gel to permit direct radioactive quantification of hu alpha-2(I) mRNA. The amount of hu alpha-2(I) mRNA expressed in as few as 111 fibroblasts was determined reliably. In contrast, the hu alpha 2(I) mRNA from at least 5 x 10(5) fibroblasts was required for detection by Northern blot analysis developed with the same cDNA probe radiolabelled with alpha-32P-dCTP by random priming. Human bronchoalveolar lavage (BAL) fluids of six patients with fibrosing lung diseases stimulated the level of expression of hu alpha-2(I) mRNA in cultured human fibroblasts as determined by this technique. The radioactive PCR method thus quantifies hu alpha-2(I) mRNA in fibroblasts with sufficient sensitivity to study fibroblast activation in vitro and detect fibroblast stimuli in human clinical samples. PMID- 1890541 TI - Selection criteria for liver transplant donors. AB - As the number of successful liver transplants has increased, the demand for donors has outpaced the supply. Approximately 25% of patients die awaiting an appropriate donor. Current criteria for assessing potential donors need to be closely examined. Fifty-six potential donors were evaluated by our transplant team by utilizing standard liver function tests (LFT's)-SGOT, SGPT, bilirubin. Additionally, a lidocaine metabolism test was performed by giving a 1 mg/kg IV dose of lidocaine over 1 minute and measuring the accumulation of the major metabolite monoethylglycinxylidide (MEGX) at 15 minutes by fluorescent polarization immunoassay (Abbott Diagnostics, Abbott Park, IL). Previous work has suggested that a MEGX less than 50 ng/mL is associated with initial non-function. Thirty-four donors were transplanted (group I) and all had initial function (all MEGX values were greater than 50). Twenty-two donors (39%) were judged unacceptable (group II) by our transplant team and by outside centers based upon one of the following criteria: II A) elevated LFT's--8, 11 B) donor age--5, II C) donor instability--4, II D) no available recipient--3, II E) miscellaneous--2. Standard LFT's were not statistically different in the donors used and in those not used when excluding category II A. Six of seven donors excluded in group I had acceptable MEGX values indicating they may have been transplantable. Ten of 12 patients excluded in groups II B-D had normal LFT's and nine of 12 had acceptable MEGX values indicating they may have been transplantable also. In this era of organ shortage, a reevaluation of donor selection criteria utilizing new tests like MEGX may be necessary to meet the increased need. PMID- 1890543 TI - Validation of an immunoradiometric assay to measure plasma levels of active renin. AB - An immunoradiometric assay (IRMA) for active renin in human plasma was analytically and clinically validated. Analytical validation established 1) precision, 2) recovery, 3) linearity, 4) cross-reactivity, 5) sample stability, and 6) the validity and specificity of the 125I-labeled anti-renin monoclonal in the Diagnostics Pasteur immunoradiometric renin kit. Clinical validation included 1) establishing normal reference range for renin, 2) comparing plasma renin activity (PRA) results to immunoreactive renin levels in subjects on Upjohn research protocols, and 3) comparing the renin responsiveness of sodium replete subjects to that of sodium deplete subjects prior to, during, and after infusion with Upjohn renin inhibitory peptide, ditekiren. This study was undertaken to demonstrate the research validity of an assay tool for the differentiation of enzymatically active renin from inactive renin or a form of prorenin. PMID- 1890542 TI - Simple ELISA method for the evaluation of soluble HLA class I antigens in human serum. AB - A simple sandwich ELISA method has been developed for the quantification of soluble HLA class I antigens (s-HLA) in human serum. The assay utilizes the monoclonal antibody Q6/64, directed to a monomorphic determinant of the HLA alpha chain, to capture the antigen and the biotinylated NAMB1 monoclonal antibody, directed to beta 2-microglobulin, as the detection antibody. The extract of the LG-2 lymphoid cell line and pooled sera from 100 healthy subjects are utilized as standards. The arbitrary value of 100 s-HLA Relative Units/mL (RU/mL) is given to the 1:20 dilution of pooled human sera whose optical density value corresponds to the one of the extract of 1 x 10(6) LG-2 cells (6.25 micrograms/mL protein concentration). The assay is easy to perform, specific, reproducible (intra- and inter-assay variations ranging from 3.2% to 8.87%), sensitive (detection limit of 6 RU/mL), and needs a small amount of serum (0.1 mL). The mean serum levels of s HLA found in 100 healthy normal subjects are 41.9 +/- 13.4 RU/mL. The potential uses of the method are discussed. PMID- 1890544 TI - Direct enzyme-linked immunosorbent assay: a simple immunoassay using Leishmania donovani promastigote for diagnosis of kala-azar. AB - For immunodiagnosis of kala-azar enzyme-linked immunosorbent assay (ELISA) and immunofluorescence testing (IFAT) are commonly used. In IFAT, whole parasite antigen and in ELISA the soluble antigen have been used. Preparation of ELISA antigen has certain inherent difficulties. We have developed a simple, specific, and quantitative immunoassay, "direct ELISA" for diagnosis of kala-azar. Intact formalinized promastigote suspension has been used to combine with the antibodies of the patient sera. The colour developed in the supernatant by the enzyme conjugate combined on the parasite surface was measured with a spectrophotometer. The test was able to detect kala-azar-specific antibodies at very high serum dilution and could discriminate between kala-azar and the common diseases prevalent in Asia. The optical densities of the sera of different control groups were significantly low. The method has potential for use as a diagnostic tool in less well equipped laboratories. PMID- 1890545 TI - Wegener's granulomatosis, ANCA, and microscopic polyarteritis. PMID- 1890546 TI - The formation and fate of glomerular immune complex deposits. PMID- 1890547 TI - An outbreak of aflatoxicosis and boric acid poisoning in Malaysia: a clinicopathological study. AB - An outbreak of food poisoning resulting in 13 deaths in children occurred in Malaysia during the Chinese Festival of the Nine-Emperor Gods in 1988. The offending food was a Chinese noodle called 'Loh See Fun' (LSF). The source was traced to a factory where a banned food preservative was added to make the LSF. The food poisoning was attributable to aflatoxins and boric acid. The clinical features included vomiting, pyrexia, diarrhoea, abdominal pain, anorexia, giddiness, seizures, and eventual coma. Initially, many presented with a Reye like syndrome. Eleven post-mortem examinations were performed. The pathological findings included extensive coagulative necrosis of the liver with proliferative 'ductal/ductular metaplasia of the hepatocytes'. Giant cell formation, central vein sclerosis, bile stasis, and steatosis were also noted. There was presence of acute tubular necrosis, superficial upper gastrointestinal erosions, and ensuing encephalopathy. The eventual cause of death is acute hepatic and renal failure. PMID- 1890548 TI - The topographical and age distributions of neuroendocrine cells in the normal human appendix. AB - In order to clarify the histogenesis of appendiceal carcinoid tumours, epithelial (ENC) and subepithelial (SNC) neuroendocrine cells were counted at four sites in 50 normal appendices stained by standard argyrophil and argentaffin techniques. In general, ENC were present in similar number at all sites within the appendix, whereas SNC were more numerous at the tip than at the base. The number of ENC was similar throughout life, apart from an increase in one neonate and some elderly patients, whereas SNC were maximal in young adults. Thus, the topographical and age distributions of SNC, but not those of ENC, parallels the topographical and age incidence of appendiceal carcinoid tumours, suggesting that most appendiceal carcinoid tumours arise from SNC rather than ENC. PMID- 1890549 TI - The vascularity of primary cutaneous melanoma. AB - In primary cutaneous malignant melanoma, the vascularity of the dermis immediately deep to the lesion may relate to tumour aggressiveness and to prognosis. These newly formed dermal vessels are incorporated into the melanoma to form the tumour microcirculation. We have assessed the percentage vascular volume in a series of primary melanomas in order to investigate the relationship between tumour vascularity and maximum tumour thickness. For the 64 melanomas included in this study, there appeared to be a significant relationship between the percentage vascular volume and the maximum tumour thickness. This relationship was not influenced by the presence of necrosis, vascular invasion, regression, or lymphocytic infiltrate, nor by the growth phase of the tumour. However, the percentage vascular volume was very low in the occasional thick melanoma, at least one of which was associated with prolonged survival. It seems possible that a low tumour vascularity could correlate with a relatively favourable outcome in cutaneous melanoma. PMID- 1890550 TI - Immunocytochemical observations on macrophage populations in normal fetal and adult human liver. AB - Phenotypic expression of macrophages was studied immunocytochemically in 25 human fetal livers at various stages of development and in 20 normal human adult livers. A panel of commercially available polyclonal and monoclonal antibodies (KP1, Mac387, LN3, CR3/43, and antibodies against muramidase, alpha-1 antitrypsin, and factor XIIIa) was applied to paraffin sections. From the seventh week of gestation macrophages in the fetal liver showed differences in distribution with the various antibodies. Macrophages in adult liver similarly varied in morphology and phenotypic expression. In the light of these results, we conclude that the population of human liver macrophages is heterogeneous from an early stage of fetal development and that this heterogeneity extends into adult life. PMID- 1890551 TI - Histopathological studies on the local reactions induced by complete Freund's adjuvant (CFA), bacterial lipopolysaccharide (LPS), and synthetic lipopeptide (P3C) conjugates. AB - The inflammatory reactions following subcutaneous application of adjuvants revealed characteristic pathological patterns. The injection of complete Freund's adjuvant (CFA) resulted in the formation of large lipid deposits encircled by an inflammatory reaction and concentrically arranged collagen bundles. Bacterial lipopolysaccharide (LPS) caused granulomatous aggregations of mononuclear cells with thrombotic vessel occlusions. Inoculation of the lipopeptide adjuvants induced accumulation of mononuclear cells with only minimal fibrotic changes which were resolved after day 28. Lipopeptide conjugates based on the head group tripalmitoyl-S-glyceryl-cysteinyl-serin (P3CS) can thus be used as effective immunogens and adjuvants without long-term tissue damage. PMID- 1890552 TI - Phenotypic modulation in lipocytes in experimental liver fibrosis. AB - The presence of a-smooth muscle actin (smA)-positive cells has recently been reported in the fibrotic liver. Lipocytes have been considered to play important roles in hepatic fibrosis. However, the relation of the a-smA-positive cells and lipocytes has not been determined. The biological implication of a-smA expression remains unknown. To study these questions, we carried out double immunofluorescent staining of a-smA and desmin (a marker for lipocytes), or a-smA and collagen, and double immunohistochemical staining of a-smA and 5-bromo-2' deoxyuridine (BrdUrd) in carbon tetrachloride-induced fibrotic rat livers. In normal and control livers, a-smA-positive cells were not seen in the lobules, whereas scattered desmin-positive cells were present. With the development of hepatic fibrosis, a-smA was expressed only in a portion of desmin-positive cells located predominantly around collagen bundles. A number of a-smA-positive cells in the lobules were labelled with BrdUrd. These results suggest phenotypic modulation in lipocytes and differentiation of lipocytes towards myofibroblast like cells, since a-smA is expressed with desmin in myofibroblasts in scar tissue. The expression of a-smA may be related to events of the fibrotic process, such as tissue contraction or fibrogenesis per se. PMID- 1890553 TI - An opinion: the role of the intercalated pathology degree. PMID- 1890554 TI - Children's conceptions of AIDS: a developmental analysis. AB - Examined causal reasoning about AIDS in children representing three major phases of cognitive development: prelogical, concrete logical, and formal logical thinking. 60 Ss (age groups: 5-7 years, 8-10 years, and 11-13 years) were administered the Concepts of AIDS Protocol. Responses were scored using the developmentally ordered Concepts of Illness Category System. The data confirm that, as a group, children's causal thinking about AIDS parallels the ways in which children think about illness in general. More specifically, the data could be organized in terms of 6 major categories or ways in which children conceptualize AIDS and its causes. The findings provide an initial empirical foundation for AIDS education curricula. PMID- 1890555 TI - Knowing someone with AIDS: the impact on adolescents. AB - Tested 25 adolescents who reported knowing a person with AIDS or HIV (PWA) and were matched by gender, race, grade, school type, and academic achievement with 25 adolescents who reported not knowing a PWA. The groups were compared with respect to their knowledge, beliefs, and social anxiety about AIDS and with respect to their worries about personal vulnerability to HIV infection. Social anxiety was significantly lower in those reporting knowing someone with AIDS than in the matching group. No significant differences between the two groups were found for knowledge, beliefs, or vulnerability worries. The implications of these findings for research on AIDS interventions with adolescents are discussed. PMID- 1890556 TI - Differences in the child-rearing practices of parents of children with cancer and controls: the perspectives of parents and professionals. AB - Obtained self-reports of parenting practices from fathers and mothers of 24 children with cancer, and 24 controls using the Child-Rearing Practices Report (CRPR). Cancer patients were primarily in long-term remission and represented a typical pattern of childhood malignancies. Same age/sex controls were recruited from the classrooms of the children with cancer. In addition, CRPR ratings were obtained from experts in pediatric oncology based upon their prediction of how a parent of a child with cancer would respond. The experts predicted differences in the areas of overinvolvement, discipline, worry about the child, nutritional concerns, and use of supernatural explanations. Results from parents showed surprising similarity between the parents of children with cancer and control parents, and disagreement with the experts. Discussion focuses on explanations for this apparent contradiction. PMID- 1890557 TI - Peer relationships and adjustment in children with cancer. AB - Evaluated the psychosocial adaptations of children with cancer (n = 24, ages 8 18) as compared with same classroom controls on indices of (a) peer- and self perceptions of sociability, aggression, and social isolation; (b) overall popularity; (c) mutual friendships; (d) feelings of loneliness; and (e) self concept in multiple domains. Although the peer report data showed that children with cancer had a social reputation as significantly more socially isolated, no significant differences were found for their popularity, number of mutual friends, loneliness, or self-worth. Findings suggest that children with cancer have a reputation as more socially isolated, but differences were not found on measures of acceptance by peers, self-concept, or loneliness. PMID- 1890559 TI - Child illness, the parenting alliance, and parenting stress. AB - Assessed relationship between children's minor illnesses during the first 3 years of life and parenting stress in the 4th year. Also examined whether a good parenting alliance would compensate for or moderate this relationship. Parents of 56 3- to 4-year-olds completed parenting alliance and stress questionnaires. Child morbidity, assessed from medical records, was directly related to mothers' but not fathers' feelings of stress. The parenting alliance was more strongly related to parenting stress for fathers than for mothers. However, child morbidity and parenting alliance interacted in predicting child-related paternal stresses. While fathers in a poor alliance reported more stress, stress was unrelated to their children's illnesses; for fathers in a moderate to strong alliance, illness and stress were positively correlated. Even minor child illnesses appear to be a source of stress for parents. PMID- 1890558 TI - Negative life events and symptom resolution in pediatric abdominal pain patients. AB - Investigated relation of negative life events (NLE) to initial symptom severity and symptom resolution at 3 months in 2 patient groups: (a) recurrent abdominal pain (RAP) without identifiable organic etiology, (b) abdominal pain with organic diagnosis. Symptoms assessed were abdominal pain, somatization symptoms, anxiety, depression. Number of NLE was positively correlated with anxiety and depression in both groups at clinic visit. NLE predicted resolution of abdominal pain for RAP patients only; RAP patients with more NLE prior to or following the clinic visit were more likely to maintain their abdominal pain. More NLE following clinic visit was associated with maintenance of anxiety and somatization symptoms at follow-up in RAP patients. Results suggest a measure of NLE is not useful in differential diagnosis of patients with and without organic findings, but is useful in predicting outcome in patients without organic findings. PMID- 1890560 TI - Antifungal activity of murine polymorphonuclear neutrophils against Histoplasma capsulatum. AB - Murine polymorphonuclear neutrophils (PMN) were examined for fungicidal and fungistatic activity against yeast cells of Histoplasma capsulatum. In a 16-h limiting dilution assay (LDA) (constant number of PMN versus decreasing numbers of yeast cells) where PMN to yeast cell ratios were high (0.4-1.5 x 10(5):1), murine PMN exhibited a limited fungicidal effect on H. capsulatum as measured by sterilization of cultures containing one to four yeast cells. On the other hand, inoculum colony forming units (c.f.u.) of H. capsulatum were not reduced by PMN in short-term (2 h) assays (PMN to yeast cell ratio, 500:1) even though H. capsulatum stimulated a brisk oxidative burst in PMN. In the same assays 84% of Candida albicans cells were killed. These findings indicate that H. capsulatum was resistant to killing by products of the oxidative burst generated by PMN and that it was slightly sensitive to PMN in 16-h LDA assays where a different microbicidal mechanism may be operative. In long-term co-culture assays, where the PMN to yeast cell ratio was 500:1, PMN consistently inhibited the replication of H. capsulatum after 24, 48, or 72 h of incubation. Inoculum c.f.u. failed to increase significantly in co-cultures, whereas in culture medium alone c.f.u. increased several-fold in 72 h. Based on these novel findings, we speculate that PMN might play a role in resistance to H. capsulatum due to their strong fungistatic activity and to a lesser extent their limited fungicidal action. PMID- 1890561 TI - Phenotypic variation of a virulent Candida albicans strain and two spontaneous, relatively avirulent mutant strain derivatives. AB - The effect of media and temperature of incubation on colony phenotype of Candida albicans strain 4918, and two relatively avirulent mutant strains, designated 4918-2 and 4918-10, has been investigated. In addition, the strains were characterized on the basis of morphotyping pattern. Colony phenotypes were determined for cultures grown on either Lee's medium supplemented with arginine and zinc, or M63 medium supplemented with casamino acids. Incubation was at either 24 or 37 degrees C for 7 days. The results demonstrated that the predominant colony phenotype observed at 24 degrees C was different from that at 37 degrees C for all three strains, irrespective of the medium. While the growth medium influenced the specific colony phenotypes observed, as well as their categorical distribution, no significant medium effect on switching frequency was apparent. The switching repertoire of strain 4918-10 was consistently more varied than either the parental strain or 4918-2 under the conditions examined. However, categorization of the colony phenotypes shown by the three strains suggested that the pattern exhibited by strain 4918-2 was distinct from that of the other two strains. In addition, individual primary colonies of each phenotype observed were clonally plated in order to examine further the switching frequencies. The results established that all three strains were capable of high frequency switching. Other experiments demonstrated that morphotypes of all three strains were different from one another as expected from the differences in their virulence reported previously. PMID- 1890562 TI - Individual differences in tumour necrosis factor and interleukin-1 production induced by viable and heat-killed Candida albicans. AB - The in vitro production of tumour necrosis factor (TNF) and interleukin-1 (IL-1) by peripheral blood mononuclear cells from 27 healthy women in response to viable and heat-killed Candida albicans was measured. Production of both cytokines was proportional to the concentration of viable C. albicans and increased at a steady rate for at least 24 h. No relationship was observed between the levels of IL-1 and TNF produced by the mononuclear cells from any individual. Some women were high TNF producers and low IL-1 producers or vice versa. Higher levels of TNF were induced by heat-killed C. albicans than by viable organisms in 26 of the 27 subjects. In marked contrast, IL-1 was induced preferentially by viable C. albicans in 23 of the 27 women. Thus, TNF and IL-1 production induced by C. albicans appears to be non-coordinately regulated and may involve different Candida moieties. PMID- 1890563 TI - Secreted Candida albicans phospholipases: purification and characterization of two forms of lysophospholipase-transacylase. AB - Candida albicans secreted three types of phospholipase (lysophospholipase, lysophospholipase-transacylase and phospholipase B) at different rates in culture. Clinical isolates of C. albicans showed variable activities of these phospholipases. Two forms of lysophospholipase-transacylase (LPTA) were purified to homogeneity from the culture filtrate of C. albicans 3125. The two purified enzymes, designated LPTA-I and LPTA-II, showed some differences in molecular mass (81 kDa for LPTA-I and 41 kDa for LPTA-II), amino acid composition and enzymatic properties. Antibody raised against purified C. albicans LPTA-II reacted strongly with LPTA-II, but not with LPTA-I. Furthermore, the biochemical properties of C. albicans lysophospholipase-transacylase were distinct from those of the corresponding mammalian enzyme. PMID- 1890564 TI - Prosthetic valve endocarditis due to Thermomyces lanuginosus Tsiklinsky--first case report. AB - The first case of Thermomyces lanuginosus endocarditis occurring on a porcine heterograft prosthesis, secondary to a Staphylococcus aureus infection of the aortic valve, is reported. The diagnosis was made post-mortem by direct examination of the prosthesis and culture of surgical samples on Sabouraud's agar. Identification was based on the presence of warty, dark brown aleurioconidia. The route of contamination could not be established but the most likely cause was the air of the operating room or the insertion of a contaminated graft. PMID- 1890565 TI - Black grain eumycetoma (Madurella mycetomatis) in the abdominal cavity of a dog. AB - A uterine stump granuloma was surgically removed from a sterilized bitch. Histopathology and fungal culture revealed Madurella mycetomatis eumycetoma. Infection may have occurred through a cesarean wound dehiscence. Long-term fluconazole therapy was instituted but failed to arrest and eliminate the infection. PMID- 1890566 TI - Theoretical analysis of H-Horn annular phased array system for heating deep seated tumors. AB - This paper discusses a type of annular phased array system--H-Horn APA. The phase and amplitude control of power deposition patterns for this system are theoretically analyzed at a frequency of 200 MHz. The formulas for calculating E field and SAR for this APA system are derived, and can be applied to other type APA systems. Models of computerized tomography (CT) scans from liver and lung regions have been used, respectively, for predicting optimization of E-field and SAR patterns in the case of the relative phase and amplitude changes. It is shown that the techniques of the phase and amplitude control of SAR patterns result in more selectively and effectively heating of tumors situated eccentrically and deeply within bodies of patients. The APA hyperthermia described in this paper shows great promise, and it looks very useful for developing clinical applications. PMID- 1890567 TI - Lateral incomitance in exotropia: fact or artifact? AB - The prevalence of significant lateral incomitance in patients with nonparetic exotropia is reported to be 22%. We speculated that measurement artifact may be the cause for some cases of apparent lateral incomitance. We measured the effective power of plastic ophthalmic prisms using a helium-neon laser in the frontal plane position and at 10 degrees, 20 degrees, and 30 degrees of rotation from the frontal plane. The rotated prisms represented the situation in which a neutralizing prism rotates with the head during measurement of lateral gaze positions. For prisms of 35 prism diopters or more, even 10 degrees of rotation produced significant artifactual incomitance. For smaller prisms, 20 degrees or more of rotation was necessary to induce significant lateral incomitance. We prospectively measured 40 consecutive patients with exotropia. Only three patients (9%) had true incomitance greater than 5 delta, and only one had incomitance in both directions of gaze. Significant lateral incomitance could be induced in every patient examined by improperly positioning the neutralizing prism. Because the detection of lateral incomitance causes most strabismus surgeons to reduce the amount of surgery they perform, special care is necessary when measuring deviations in lateral gazes. PMID- 1890568 TI - Stereopsis testing to reduce overreferral in preschool vision screening. AB - Three- and 4-year-old children who obtain the minimum failing visual acuity result of one-line difference between eyes in preschool vision screening with isolated optotypes have a high rate of overreferral. We evaluated the Random Dot E Stereotest (RDES) to determine if a passing result at a high threshold on this test, as administered by lay screeners, could safely nullify referral for a minimum failing visual acuity test result. Fifty-eight children with a "one-line difference" result also had the RDES administered to them during screening at distances of 40 cm and 1.5 m. Upon subsequent ophthalmologic examination, 45 of these children were found to be normal, and 13 had abnormal findings. Thirty-nine of the children with normal examinations had correctly passed the RDES at 1.5 m. Seven of the 13 children with abnormal findings had correctly failed the RDES. Thus, the specificity of stereotesting was 87% and the sensitivity was 54%. Among the six children who falsely passed the stereopsis test during screening, best corrected visual acuity was no worse than 20/40 and no child had greater than a one-line difference in acuity. Therefore, no amblyopia was missed. If a passing result on the stereotest at 1.5 m had been allowed to nullify a one-line difference referral, overreferral would have decreased 87% but underreferral would have increased 46%. We cannot yet recommend modifying current visual acuity referral criteria based on stereopsis testing results until the sensitivity of stereopsis screening by lay screeners at a sufficient threshold is improved. PMID- 1890569 TI - Unexpected good results after therapy for anisometropic amblyopia associated with unilateral peripapillary myelinated nerve fibers. AB - Unilateral extensive myelination of the peripapillary nerve fibers may be associated with anisometropic myopia, strabismus, and reduced vision. Despite aggressive occlusion of the normal eye, visual results are often disappointing, presumably due to associated structural abnormalities in the macula which limit visual potential. We report two cases, a 21-month-old child and a 23-month-old child with unilateral peripapillary myelination, ipsilateral high myopia, and dense amblyopia. Despite an abnormal macular reflex in each child, vision improved to 20/30 in one child and 20/50 in the other child after occlusion therapy. Visual results in these patients suggest that aggressive amblyopia therapy should be considered in patients with anisometropic amblyopia associated with extensive myelination continuous with the optic nerve. Not all patients with unilateral peripapillary myelinated nerve fibers, an abnormal macula, and myopia will have refractory amblyopia. PMID- 1890570 TI - Clinical characteristics and surgical treatment of intermittent esotropia. AB - This study describes the age of onset, symptomatology, and clinical characteristics of 25 patients with intermittent esotropia. This subgroup of esotropic patients typically has onset prior to 10 years of age and shows excellent bifoveal fixation ability, reflected by a high degree of stereopsis. In contrast to patients with other forms of esotropia, there is minimal to no hyperopia, an average esodeviation of approximately 20 prism diopters, and a low incidence of amblyopia, DVD, and oblique overaction. Symptomatic diplopia or cosmetic concern necessitated surgical intervention in 17 (68%) patients. Fifteen (88%) patients had good or excellent surgical results of either orthophoria, esophoria, or residual esotropia of 10 delta or less. One patient (6%) had residual esophoria greater than 10 delta. One patient had 4 delta of exophoria postoperatively. Intermittent esotropia should be differentiated from the various entities of microtropia, fixation disparity, and monofixation syndrome. PMID- 1890571 TI - Management of posterior lenticonus. AB - Posterior lenticonus is associated with progressive lens opacification. We report a series of 40 consecutive patients (41 eyes) with posterior lenticonus who were treated by three pediatric ophthalmologists between 1974 and 1988. Prior to cataract surgery, appropriate patients were treated with atropine dilatation, spectacle correction including bifocals for refractive errors, and amblyopia occlusion therapy. Indications for surgery were a measured decrease in visual acuity, the loss of a central fixation reflex, or the onset of strabismus. The age at which cataract surgery was performed ranged from 2 months to 12 years (mean 4 years, 6 months). Nineteen eyes (49%) achieved postoperative acuities in the 20/20 to 20/40 range, 7(18%) eyes achieved 20/50 to 20/100, 4 (10%) eyes achieved 20/200, and 4 (10%) eyes achieved less than 20/200. Two (5%) young patients had central, steady, and maintained visual fixation reflexes and 3 (8%) additional patients had central, steady, but not maintained reflexes. After cataract surgery and aphakic optical correction, amblyopia was present in 84% of patients and strabismus was present in 51% of patients. The patients in this study had sufficient optical distortion to produce amblyopia. Cataract removal and optical correction alone did not correct the vision; occlusion therapy for amblyopia was required. Earlier surgery may be indicated to prevent visual deprivation amblyopia in patients with posterior lenticonus. PMID- 1890572 TI - Normative values for visual fields in 4- to 12-year-old children using kinetic perimetry. AB - We report normative data for 4- to 12-year-old children using a kinetic perimetry technique that employs a double arc perimeter with a 6-degree target designed for use with infants and children. The subject population consisted of 84 children in four age groups (4, 5, 7, and 10 yrs) and 21 adults as comparison subjects. Individuals had eye examinations to rule out causes of abnormal visual fields. Mean visual field size was determined separately for the right and left eyes in each age group. In the 4-year-old group, the mean extent of visual field along each of the four meridians for the right eye was 59, 48, 52, and 85 degrees of arc for radial meridians orientation set at 45, 135, 225, and 315 meridians, respectively. The visual field extent in each quadrant generally increased with age. The overall extent of field as measured along the four meridians for all subject groups increased significantly with the age, indicating a continued growth of visual field size in older children. These data suggest that adult visual field size is achieved at about 11.6 years of age. PMID- 1890573 TI - Neodymium:YAG pupilloplasty in pediatric aphakia. AB - An adequate pupillary aperture is required for accurate ophthalmoscopy and retinoscopy in pediatric aphakia. When pupillary miosis does not respond to pharmacologic dilation, optical iridectomy performed with a vitreous suction cutting instrument under general anesthesia may be required. We report a 27-month old aphakic child whose pupillary aperture was enlarged from 1 mm to 3.5 mm with neodymium (Nd):YAG pupilloplasty, following intramuscular sedation with meperidine, promethazine, and chlorpromazine. Removal of the laser chin rest and positioning of the patient on a table with adjustable height facilitated delivery of 140 applications at 2.5 to 4.3 mJ to the pupillary border. Levobunolol 0.5% controlled the transient posttreatment rise in intraocular pressure. We suggest that Nd:YAG pupilloplasty performed with sedation be considered as an alternative to intraocular surgery when pupillary miosis in pediatric aphakia does not respond to dilating agents. PMID- 1890574 TI - The ocular changes of incontinentia pigmenti achromians (hypomelanosis of Ito). AB - Incontinentia pigmenti achromians is a multisystem hereditary disorder characterized specifically by a whorled or streaked cutaneous hypopigmentation and frequently characterized by numerous neurologic, musculoskeletal, and ocular abnormalities. We present a patient with incontinentia pigmenti achromians in whom the ocular abnormalities included the commonly reported exotropia, myopia, small optic nerve, and hypopigmentation of the fundus, as well as rarely reported corneal asymmetry, pannus, and atropic irides with irregular pupillary margins. The patient also had a cataract in the right eye and a retinal detachment in the left eye. PMID- 1890575 TI - Surgical results in Brown syndrome. AB - Surgical treatment for Brown superior oblique tendon sheath syndrome, now called Brown syndrome, has been advocated for patients with abnormal head posture or manifest hypotropia in primary gaze. Several surgical procedures with variable results and complications have been reported without consensus. Techniques and results of treatment for Brown syndrome at two institutions were reviewed. Charts of all patients who had undergone surgical treatment at Texas Children's Hospital, Houston, Tex, and Riley Hospital for Children, Indianapolis, Ind, between 1965 and 1989 were reviewed. The review yielded 38 patients. Superior oblique tenectomy was the most efficacious initial procedure. Surgery was successful in the treatment of anomalous head posture associated with Brown syndrome. There was no loss of sensory function as a result of surgery, but surgery did not inevitably lead to improved sensory function. We do not advocate superior oblique weakening combined with simultaneous surgery for iatrogenic superior oblique palsy as an initial procedure for Brown syndrome, since nearly one-half of our patients did not develop superior oblique palsy when followed for more than 1 year. PMID- 1890576 TI - Strabismus following endoscopic intranasal sinus surgery. AB - Two patients developed exotropia with limited medial rectus function following endoscopic intranasal ethmoid sinus surgery. In both patients, fractures occurred in the medial orbital wall. The first patient required horizontal rectus muscle surgery to regain ocular alignment. The second required no surgery, but was left with limited horizontal motility secondary to scarring at the fracture site. While endoscopic techniques improve the surgeon's view of sinus anatomy, they do not eliminate the risk of entering the orbit and causing ocular complications. PMID- 1890577 TI - The diagnosis of amblyopia in cross-fixation. AB - Customarily, it is taught that cross-fixation, in a patient with congenital esotropia, obviates the development of amblyopia. However, our clinical experience has shown significant amblyopia in 50% of cross-fixators. In our hands, the diagnosis of amblyopia is made based on the point at which alternation of fixation takes place. By this method, if there is equal visual acuity, alternation will occur at the midline with each eye. If amblyopia exists, the sound eye will continue to follow the target beyond midline, into abduction, before the poorer seeing eye picks up fixation. In order to test the reliability of this method, using Teller acuity cards as the standard, we compared estimates of objective and subjective vision in 25 consecutive patients with congenital esotropia and cross-fixation. Our findings suggest that there may be a significant prevalence of amblyopia in cross- fixating patients and that the point at which alternation of fixation occurs is a reliable means of detecting a difference in visual acuity between the two eyes. PMID- 1890578 TI - Conjunctival mass formation with unexpected foreign body. AB - Two 4-year-old females with inferior fornix conjunctival lesions are described. Both cases proved to be cotton-material-induced granulomas. These cases are reported to emphasize that recognition of foreign body conjunctival granuloma remains as a challenge to ophthalmologists. PMID- 1890579 TI - Pseudomonas aeruginosa endophthalmitis in a premature infant. PMID- 1890580 TI - Contrast sensitivity letter charts as a test of visual function in amblyopia. PMID- 1890581 TI - Effect of depression on quantity and quality of social inferences. AB - Two studies explored depressives' sensitivity to social information as an impediment to their gaining a sense of confidence and control. In Study 1, Ss viewed a videotape of an actor performing an achievement task and were asked to list their impressions of the actor. As compared with nondepressed Ss, depressed Ss generated more inferences overall, generated more abstract inferences, and exhibited less overall confidence in their impression of the actor. In Study 2, Ss reported their beliefs of the utility of information about a person's past behaviors and personality for understanding, predicting future behavior, and describing that person. Depressed Ss expressed more interest than did nondepressed Ss in both types of information but were less confident of the utility of the information for prediction. PMID- 1890582 TI - A prospective study of depression and posttraumatic stress symptoms after a natural disaster: the 1989 Loma Prieta Earthquake. AB - Measures of emotional health and styles of responding to negative moods were obtained for 137 students 14 days before the Loma Prieta earthquake. A follow-up was done 10 days again 7 weeks after the earthquake to test predictions about which of the students would show the most enduring symptoms of depression and posttraumatic stress. Regression analysis showed that students who, before the earthquake, already had elevated levels of depression and stress symptoms and a ruminative style of responding to their symptoms had more depression and stress symptoms for both follow-ups. Students who were exposed to more dangerous or difficult circumstances because of the earthquake also had elevated symptom levels 10 days after the earthquake. Similarly, students who, during the 10 days after the earthquake, had more ruminations about the earthquake were still more likely to have high levels of depressive and stress symptoms 7 weeks after the earthquake. PMID- 1890583 TI - Promoting systematic processing in low-motivation settings: effect of incongruent information on processing and judgment. AB - Ss received consensus information that was either congruent or incongruent with the valence of persuasive message content. In Experiment 1 Ss believed that their processing task was either important or unimportant whereas in Experiment 2 all Ss believed that their task was unimportant. In accord with the heuristic systematic model's sufficiency principle, high-task-importance Ss exhibited a great deal of systematic processing regardless of congruency, whereas low importance Ss processed systematically only when they received incongruent messages; in the congruent conditions heuristic processing dominated. Attitude data generally reflected these processing differences and confirmed the additivity and attenuation assumptions of the model. The utility of the sufficiency principle for understanding motivation for elaborative processing and the relevance of the findings to understanding the processing and judgmental effects of expectancy disconfirmation are discussed. PMID- 1890584 TI - Personality and susceptibility to positive and negative emotional states. AB - Gray's (1981) theory suggests that extraverts and neurotics are differentially sensitive to stimuli that generate positive and negative affect, respectively. From this theory it was hypothesized that efficacy of a standard positive-affect induction would be more strongly related to extraversion than to neuroticism scores, whereas efficacy of a standard negative-affect induction would be more strongly related to neuroticism scores. Positive and negative affect was manipulated in a controlled setting, and the effectiveness of the mood induction was assessed using standard mood adjective rating scales. Results are consistent with the hypothesis that neurotic Ss (compared with stable Ss) show heightened emotional reactivity to the negative-mood induction, whereas extraverts (compared with intraverts) show heightened emotional reactivity to the positive-mood induction. Results corroborate and extend previous findings. PMID- 1890585 TI - Stress specificities: differential effects of coping style, gender, and type of stressor on autonomic arousal, facial expression, and subjective feeling. AB - In this study several factors considered to be relevant in mediating stress arousal were experimentally manipulated. Ss selected for the coping styles anxiety denying, low anxiety, and high anxiety were confronted with both low- and high-arousal-inducing situations, using 2 different types of stressors (cognitive vs. emotional) in each case. Arousal reactions were measured in 3 response modalities: verbal report of subjective experience; nonverbal, nonvocal behavior; and physiological reactions. The results reveal complex interactions between type and degree of stress, coping style, and gender of Ss, confirming findings on vocal parameters of stress. These complex interactions are discussed with respect to the possibility that Ss' evaluation of situation characteristics may be influenced by coping styles and gender, resulting in differential reaction patterns. PMID- 1890586 TI - Individual differences are accentuated during periods of social change: the sample case of girls at puberty. AB - The emergence of new behaviors and the reorganization of psychological structures are often attributed to critical events and crises in the life course. A fundamentally different perspective is offered: Potentially disruptive transitions produce personality continuity, not change. The behavioral responses of adolescent girls to the onset of menarche was studied in a longitudinal study of an unselected birth cohort. Predictions from 3 rival hypotheses about the relation between pubertal change and social psychological change were first tested: the stressful change, off time, and early-timing hypotheses. The results supported the early-timing hypothesis. Whether stressful, early menarche generated new behavioral problems or accentuated premenarcheal dispositions was then tested. The results supported an accentuation model: Stressful transitions accentuated behavioral problems among girls who were predisposed to behavioral problems earlier in childhood. Speculations are offered for a broader theory about the role of individual differences in the life course. PMID- 1890587 TI - The perceived causal structure of loneliness. AB - Two studies examined the way people represent the causes of loneliness as a semantic space and as a causal network. In a multidimensional scaling task, the results of Michela, Peplau, and Weeks (1982) were replicated and the causes wee classified according to locus and stability. In a 2nd study, 44 people judged the likelihood that these causes were interconnected. From these data, a causal network or perceived causal structure (Kelley, 1983) was derived by means of network analysis. The structure revealed a complex lay theory of loneliness in which personality influenced group behavior, which in turn influenced psychological states and beliefs. States and beliefs were also affected by physical features and situational factors. PMID- 1890588 TI - Gender gaps: who needs to be explained? AB - The hypothesis that explanations for differences between prototypical and nonprototypical members of categories would focus more on attributes of the latter than on those of the former was examined. Explanations for alleged gender differences in the behavior of voters, elementary school teachers, and college professors were elicited. As predicted, explanations for gender differences within the 3 categories emphasized the qualities of the "deviant" member. Ss' explanations of alleged gender gaps in the behavior of voters and college professors focused more on qualities of women than on qualities of men. In contrast, Ss' explanations of an alleged gender gap in the behavior of elementary school teachers focused more on qualities of men than on qualities of women. The results are interpreted in terms of Kahneman and Miller's (1986) norm theory. PMID- 1890589 TI - Self-derogations and the interpersonal theory. AB - The interpersonal theory of personality has been applied to explain depressed people's dilemma: The depressed person's submissive behavior invites dominating reactions from other people, and those reactions sustain the depressed person's depression. Experiments 1 and 2 showed that self-derogations connote submissiveness but are generally judged to be neutral in affiliation. Experiment 3 tested implications for the behavior of dysphoric and nondysphoric Ss as they interacted with a self-derogating, other-derogating, or nonderogating confederate partner. Ss selected a topic from a list and talked about it for 1 min: the confederate's script was fixed. The S's judgments of the confederate, choice of topics, satisfaction with the interaction, and actual responses were analyzed. Self-derogators were judged to be submissive, elicited dominating reactions, and selected more topics with negative content. PMID- 1890590 TI - Stability of self-esteem as a moderator of the relation between level of self esteem and depression. AB - The hypothesis that stability of self-esteem would moderate the predictive relationship between level of self-esteem and depression was tested. Specifically, level of self-esteem was hypothesized to relate more strongly to subsequent depression for individuals with stable self-esteem than for individuals with unstable self-esteem. Results strongly supported this hypothesis. Implications for the relation between level of self-esteem and depression, and for the moderator variable approach to personality and prediction, are discussed. PMID- 1890591 TI - Modeling the relations of attributional style, expectancies, and depression. AB - Structural modeling techniques were used to assess relations of attributional style, expectancies, and depression. According to an initial theoretical model, attributions are directly related to expectancies, and expectancies are directly related to depression, but attributions are only indirectly related to depression by means of their relation to expectancies. The results of Study 1 indicated that this model was flawed in 2 respects: (a) Attributions for positive and negative events did not form a single latent variable, and (b) attributions for negative events both were indirectly related to depression by means of expectancies and were directly related to depression. Attributions for positive events only were indirectly related to depression by means of expectancies. The model derived in Study 1 was replicated in Study 2. Discussion centers on the interpretation of this modified model and on issues in the measurement of attributional style. PMID- 1890592 TI - Self-reported sleep quality in HIV infection: correlation to the stage of infection and zidovudine therapy. AB - We investigated self-reported sleep quality in a group of 50 patients in different stages of HIV-1 infection by using a standardized questionnaire (Pittsburgh Sleep Quality Index). Alterations of sleep were found to be significantly correlated with the most severe stage of infection in AIDS patients. Analysis of data failed to indicate a significant influence of zidovudine on self-reported sleep quality. PMID- 1890593 TI - Anergy and AIDS. PMID- 1890594 TI - Detection of human immunodeficiency virus by virus culture and polymerase chain reaction in children born to seropositive mothers. PMID- 1890595 TI - HIV-1 infection, tuberculosis, and syphilis in male transsexual prostitutes in Milan, Italy. PMID- 1890596 TI - HIV infection in the blood donors of Delhi, India: 1 1/2 years' experience. PMID- 1890597 TI - The epidemiology of AIDS in the New York and California Medicaid programs. AB - An epidemiological analysis of the impact of AIDS on the New York and California Medicaid programs was conducted for 1983-1986. The epidemic affected the New York and California Medicaid programs in several similar ways. The total number of cases grew rapidly over the study time period. In both states, the epidemic was mostly confined to the young adult (21-44 years) age group. Cases were geographically concentrated and highly localized even within counties, but evidence of geographic dispersion to counties outside of the urban centers was also evident. Some dramatic differences were also found between California and New York. Patients with claims histories of drug use were far more likely to be found in the New York population and the proportion of other adult males (our proxy for the homosexual risk group) was higher in California. A much higher proportion of New York's population was female (30 vs. 5%). New York also had many more pediatric cases. Most importantly, New York's raw number of cases was substantially higher than California, with approximately three times as many cases during the time period (1983-1986). There is also substantial evidence that transmission of the disease to heterosexual partners of drug users places heterosexual urban minorities at grave risk of contracting the disease through interaction with infected persons. PMID- 1890598 TI - Medicaid eligibility patterns for persons with AIDS in California and New York, 1982-1987. AB - An analysis of Medicaid eligibility patterns for persons with AIDS (PWAs) was conducted, based on the longitudinal Medicaid eligibility histories of 1,314 AIDS decedents in California and 6,273 AIDS decedents in New York between 1982 and 1987. The study analyzed what eligibility groups or categories and which financial standards PWAs were using to qualify for Medicaid. States have many options with regard to the categories of people they cover under Medicaid and where they set their financial thresholds. The study findings are useful in showing how these policy decisions affect PWAs. A major conclusion of the study is the importance of medically needy coverage for PWAs. Medically needy coverage, which is optional to states, opens up Medicaid to persons of any income level, assuming their medical expenses are high enough. The study also found that PWAs who qualify only through the medically needy provisions have much shorter enrollment and lower lifetime Medicaid expenditures than other PWAs on Medicaid. Presumably, most medically needy only enrollees have other sources of health care coverage in the early stages of the illness. Study data also suggested significant administrative obstacles for PWAs in dealing with the Medicaid eligibility process. Finally, an unexpected study result was that all states may not be aggressively utilizing federal Medicaid financing options for covering the medical assistance expenditures for a significant proportion of the low-income AIDS population. PMID- 1890599 TI - Lifetime Medicaid service utilization and expenditures for AIDS in New York and California. AB - Several important gaps exists in information on the health care resources used by people with AIDS, including patterns of outpatient care, differences between populations at risk of the disease, and services paid for by Medicaid. To address the shortage of information in these areas, this study examined average Medicaid expenditures and service use for the time period a person has AIDS. The study population was Medicaid enrollees with AIDS in New York and California who died between October 1985 and September 1986. The study focused on the differences between the two states and between four groups that were proxies for at-risk populations: children, women, drug-using men, and non-drug-using men. Mean lifetime Medicaid expenditures were about $30,000 in New York and $20,000 in California. Inpatient use was higher and outpatient service use was lower in New York than in California after controlling for risk group, diagnosis, and Medicaid eligibility group (a proxy for income level). In California, women had higher expenditures and inpatient use than men. In New York, women and drug-using men had higher expenditures and use of inpatient and outpatient services (except home health care) than the non-drug-using men. Children in New York had higher expenditures and hospital use than adults but similar outpatient service use. Multivariate analyses suggest that differences between risk groups were largely attributable to differences in diagnosis and income level (as measured by Medicaid eligibility group). PMID- 1890600 TI - The AIDS-defining diagnosis and subsequent complications: a survival-based severity index. AB - To define a survival-based severity measure for AIDS, we convened a panel of AIDS experts who identified factors influencing AIDS prognosis and estimated the impact of prognostic factors on survival time. The resulting conceptual model included 19 AIDS-defining conditions and 80 subsequent AIDS-related complications. This model was tested on longitudinal disease histories of 3,937 AIDS patients in the New York State Medicaid Program diagnosed between 1983 and 1986 and followed through 1988. The initial AIDS diagnosis and complications within 3 months of AIDS onset were identified from coded diagnoses recorded on inpatient and outpatient claims. Three AIDS-defining diagnosis groups were created; survival times from least to most severe group were 25, 10, and 7 months. To determine the influence of subsequent complications on risk of death, the survival times associated with combinations of defining diagnosis groups and four severity levels of subsequent complications were determined. Median survival ranged from 43 months for the least severe defining diagnosis group without early complications to 12 months for the group with severe defining diagnoses and serious complications. The matrix of AIDS-defining diagnoses and complications was divided into four severity categories with significantly different survival curves. This severity measure uses longitudinal data commonly available to clinicians and researchers to create distinct AIDS prognostic categories. PMID- 1890601 TI - HIV antibody status and employment discrimination: 1991 update. PMID- 1890602 TI - Jejunal biopsy in HIV-infected patients. AB - Forty-nine HIV-infected patients were submitted to peroral jejunal biopsy in order to evaluate the presence of microorganisms and the histomorphometric aspects of the enteric mucosa with subsequent correlation of these findings to the appropriate clinical stage of the disease. Thirty-seven patients fulfilled the CDC criteria for AIDS, of whom 23 presented with diarrhea. Of the 12 patients who had not yet been given an AIDS diagnosis. 3 had persistent generalized lymphadenopathy and 9 were asymptomatic carriers. Flat mucosa was observed in two patients (8.7%) with diarrhea and coccidea. Subtotal villous atrophy and severe lamina propria (LP) mononuclear infiltrate (13%) were found only in patients with diarrhea. Moderate to severe histologic changes were more frequently observed in this group, not always related to the presence of microorganisms. Crypt hyperregeneration was a constant finding. Intraepithelial lymphocyte (IEL) count was decreased in patients with diarrhea. Specific infectious agents were unexpectedly rare for the tropical developing country population studied. The organism most commonly associated with diarrhea was Cryptosporidium sp. (21.7%). The etiology of diarrhea in a significant number of patients remains unclear. PMID- 1890603 TI - Sexual behaviors of intravenous drug users in treatment. AB - Sexual behaviors of a group of 313 intravenous drug users (IVDUs) (225 men, 88 women) were assessed by a structured interview at the start of an AIDS prevention project. Although the majority were celibate or monogamous during the prior year (men 52.5%, women 64.3%), many IVDUs had multiple sexual partners in that time, including 19.6% of men and 7.2% of women reporting five or more. Married male and female IVDUs were more likely to have multiple sexual partners than married people in general population samples. Only 38.5% of male and 35.4% of female IVDUs ever used condoms during the previous 5 years. Percentage of sexual encounters in which condoms were used correlated significantly with the number of partners for women (r = 0.37, p less than 0.01), but not for men (r = 0.03, ns). Use of intravenous drugs in the prior year, sharing of needles, use of stimulants, exchange of sex for money or drugs, and combining sexual events with drug use were all associated with greater numbers of sexual partners. A subset of male IVDUs engages in the dual-risk behaviors of needle sharing and unprotected intercourse with multiple partners. This group could act as a highly efficient vector for human immunodeficiency virus transmission and should become a focus of intensive preventive intervention. PMID- 1890604 TI - An open-label, dose-ranging trial of AL 721 in patients with persistent generalized lymphadenopathy and AIDS-related complex. AB - AL 721, a lipid mixture with reported in vitro activity against human immunodeficiency virus (HIV) via cell membrane or virion cholesterol depletion, was evaluated in a multicenter, open-label, dose-ranging trial. Forty men with persistent generalized lymphadenopathy or AIDS-related complex were treated with doses of 20, 30, 40, or 50 g orally twice daily for 8 weeks, and monitored for toxicity, disease progression, and with immunologic, virologic, and serum lipid profiles. The compound was found to be well tolerated over the broad range of doses examined; adverse reactions were confined to the gastrointestinal tract, of mild to moderate severity, and self-limited in duration. Modest weight gains observed on treatment were reversed within 4 weeks following cessation of therapy. While disease progression was not observed in this short-term study, we could find no indication of an immunorestorative or antiviral effect of AL 721, as determined by T-lymphocyte subset quantitation or HIV culture. All three patients who were HIV p24 antigenemic at entry retained positive antigen levels throughout treatment. As a consequence of therapy, however, significant increases in serum lipids were observed, including elevations in both triglyceride and total cholesterol levels. In conclusion, our experience on the largest group of HIV-infected patients treated with the highest doses of AL 721 provides no support for the use of this compound as an antiretroviral agent. PMID- 1890605 TI - Liposomal encapsulation of 3'-azido-3'-deoxythymidine (AZT) results in decreased bone marrow toxicity and enhanced activity against murine AIDS-induced immunosuppression. AB - The effect of liposome encapsulation on the bone marrow toxicity and antiviral activity of AZT in C57BL/6 mice was determined. Liposomal encapsulation of AZT enhanced localization in the liver, spleen, and lung, and reduced localization in bone marrow. AZT administered i.v. (0.08-50 mg/kg/day) had significant bone marrow toxicity (30-50% reduction in cellularity) after five injections, maximum toxicity occurring at greater than or equal to 2 mg/kg/day. Parallel reductions in the number of erythrocytes and leukocytes were observed. AZT encapsulated in liposomes had no bone marrow toxicity at doses of 0.08-10 mg/kg/day, and erythrocyte and leukocyte numbers remained normal. Infection of C57BL/6 mice with LP-BM5 murine leukemia virus suppressed T- and B-cell mitogenic responses. Treatment of LP-BM5 retrovirus-infected mice with 2 mg/kg AZT three times weekly partially protected the mitogenic response at 4 but not at 7 weeks postinfection. Treatment with liposomal AZT resulted in normal T- and B-cell mitogenic responses at both 4 and 7 weeks postinfection. PMID- 1890606 TI - Relationship of serum copper and zinc levels to HIV-1 seropositivity and progression to AIDS. AB - Dietary, serum, and tissue levels of copper and zinc were determined at baseline in a cohort of homosexual men to investigate the relationship of these factors to human immunodeficiency virus type 1 (HIV-1) seropositivity and subsequent progression to AIDS. Using a nested case control design, 54 asymptomatic HIV-1 seropositives who later progressed to AIDS were compared with 54 HIV-1 seropositives who did not progress and 54 seronegatives (mean follow-up time 2.5 years). Serum levels of copper and zinc were estimated from frozen serum samples, tissue levels from stored toenail samples, and dietary intakes from a semiquantitative food frequency questionnaire administered at baseline. Neither dietary copper and zinc nor their levels in toenails were associated with HIV-1 seropositivity or progression to AIDS. However, serum copper levels were higher (p = 0.002) in HIV-1-seropositive progressors (mean = 115.6 micrograms/dl; SD = 17.1) than the seropositive nonprogressors (mean = 109.0 micrograms/dl; SD = 15.8) and the seronegatives (mean = 101.9 micrograms/dl; SD = 16.7). Conversely, serum zinc levels were lower (p = 0.016) in the seropositive progressors (mean = 85.2 micrograms/dl; SD = 11.5) than the seropositive nonprogressors (mean = 90.7 micrograms/dl; SD = 12.0) and the seronegatives (mean = 92.0 micrograms/dl; SD = 14.7). Furthermore, in a logistic regression, higher serum copper (odds ratio per 20-micrograms/dl increase = 2.23; 95% confidence interval = 1.02-4.87) and lower serum zinc (odds ratio per 20-micrograms/dl increase = 0.30; 95% confidence interval = 0.14-0.66) predicted progression to AIDS independently of baseline CD4+ lymphocyte level, age, and calorie-adjusted dietary intakes of both nutrients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1890607 TI - Alcohol consumption and unsafe sex: a comparison of heterosexuals and homosexual men. AB - Recent studies have suggested that drinking in conjunction with sexual activity is related to unsafe sexual activities known to increase the risk of AIDS transmission. However, these studies have used general measures of frequency of both drinking and sexual behavior, giving insufficient information to establish that drinking and risky sex occur in the same sexual encounters. This article presents data from a mail survey of the adult population of San Francisco in which respondents were queried about the circumstances of specific sexual encounters that took place in conjunction with alcohol consumption. The results showed that subjective intoxication was related to practice of unsafe sex among homosexual men and heterosexual women but not among heterosexual men. In addition, respondents whose sexual partners were met in locations construed as "pickup" environments were more likely to practice safe sex. A focus on specific sexual events can contribute to a better understanding of the dynamics of sexual encounters and of the predictors of risky sex in these encounters. PMID- 1890608 TI - The supply and demand dynamics of sexual behavior: implications for heterosexual HIV epidemics. AB - This article investigates the supply and demand dynamics of sexual behavior in a simple epidemiological model of heterosexual transmission of human immunodeficiency virus (HIV). The supply and demand dynamics of sexual behavior are modeled by specifying implicit sexual behavior change (ISBC) mechanisms. These mechanisms specify how males and females modify their rates of sex partner change in response to changes in the availability of the opposite sex. During an epidemic, the availability of both sexes will change owing to recruitment and mortality; consequently, implicit sexual behavior changes will be induced. These behavior changes will be independent of any explicit sexual behavioral changes that may occur as a result of intervention strategies. We investigate four different ISBC mechanisms: the two extremes of the continuum of possible mechanisms (where only one sex changes behavior), as well as two intermediate possibilities (where both sexes change behavior). The results show that the epidemiological effects of these ISBC mechanisms depend upon the transmission speed of the virus. If HIV transmission is slow, the epidemiological effects of the four ISBC mechanisms cannot be differentiated. If HIV transmission is fast, the four ISBC mechanisms differ considerably in the degree to which they modify the gender-specific rates of sex partner change, but the sexual behavioral changes occur too late to significantly decrease the cumulative number of infected persons. However, if HIV transmission is moderately fast, the four different ISBC mechanisms produce significantly different epidemics. The differences between the epidemics, produced by the four ISBC mechanisms, are magnified as the degree of asymmetry between the heterosexual transmission efficiencies increases. We discuss the implications of our results for both the future number of AIDS cases that will be observed in the "real world" and the number of AIDS cases that will be predicted from mathematical models. We also discuss the implications for studies that evaluate the causation of sexual behavior changes. PMID- 1890609 TI - Alcohol affects rat testicular interstitial fluid volume and testicular secretion of testosterone and beta-endorphin. AB - The effects of alcohol on testicular interstitial fluid (TIF) volume and the secretion of testosterone and beta-endorphin (beta E) into this important testicular compartment were assessed in the rat. Alcohol time- and dose-response curves were constructed for changes in TIF volume and the bioactive concentrations of testosterone and immunoreactive beta E (i-beta E). Alcohol (3 g/kg) decreased TIF volumes and increased TIF i-beta E secretion 0.5 to 6 hr after injection and decreased TIF testosterone 1 to 6 hr after injection. These effects were dose-related at 2 hr postinjection. The possible role of alcohol induced reductions in serum luteinizing hormone and testosterone levels in mediating the effects of alcohol on TIF volume was also examined. We found that pretreating rats with human chorionic gonadotropin, which reversed alcohol induced suppression in levels of serum gonadotropins and testosterone, failed to reverse the effects of alcohol on TIF volume and the secretion of testosterone and i-beta E. These results indicate that alcohol decreases TIF volume, inhibits TIF testosterone secretion and stimulates TIF i-beta E secretion and, furthermore, suggest that these effects are not indirectly mediated by decreased levels of gonadotropins or testosterone, but by direct effects of alcohol on gonadal function. The strong inverse correlation between TIF i-beta E and testosterone secretion after alcohol administration and previous evidence that testicular opioids inhibit the biosynthesis of testosterone suggest that alcohol may act through testicular beta E to suppress the synthesis and release of testosterone in the testes. PMID- 1890610 TI - Enhanced entry of ciprofloxacin into the rat central nervous system induced by fenbufen. AB - The effects of fenbufen on the transport of ciprofloxacin (CPFX) into the brain and cerebrospinal fluid (CSF) were investigated in rats. Periodically after a bolus i.v. dose of CPFX (10 mg/kg), alone or with fenbufen (20 mg/kg), to rats, aliquots of CSF and blood were collected and then the whole brain was readily excised from the animal after sacrifice by microwave irradiation. Serum levels of CPFX in the terminal phase were significantly elevated by the coadministration with fenbufen. However, the extent of CPFX binding to serum protein was not affected by fenbufen. Immediately after the coadministration with fenbufen, brain and CSF levels of CPFX were raised by about 15 to 70% and 70 to 100%, respectively. Both brain/serum unbound and CSF/serum unbound level ratios were increased by fenbufen at relatively early periods after drug injection. Analysis based on physiological models indicated that fenbufen significantly increased the apparent diffusion clearances of CPFX across blood-brain and blood-CSF barriers. These findings suggest that coadministered fenbufen may facilitate the entry of CPFX into the central nervous system not only by elevation of serum level but also by enhancement of permeability across the blood-brain or blood-CSF barrier. PMID- 1890611 TI - Effects of apomorphine on heart rate during simultaneous administration of sulpiride: a challenge of the composed concentration-effect model. AB - Apomorphine elicits opposite concentration-dependent effects on the heart rate in rat bradycardia at low concentrations and tachycardia at higher ones. This has been modeled with a composed sigmoid Emax equation. To challenge this model, a selective antagonist, sulpiride, was administered simultaneously with apomorphine. Four short intravenous infusions of apomorphine, at different rates, were administered to rats, while a steady state concentration of sulpiride was maintained by intravenous infusion. Another group of rats was infused with apomorphine at the same rates of infusion as in the above groups, together with saline. In this latter group a biphasic concentration-response relationship was observed, while in the group receiving sulpiride and apomorphine no bradycardia was detected. A sigmoid Emax model with one term describing bradycardia and one tachycardia was used for the saline plus apomorphine data. For the sulpiride plus apomorphine data a single-term sigmoid Emax model was used. The maximal induced tachycardia was found to be the same in both groups. The tachycardia occurred at lower concentrations in the sulpiride group, probably as a result of an antagonist-induced shift of the bradycardia towards higher concentrations. The obtained results show that a composite concentration-effect curve of apomorphine has experimental validity and that it is possible to separate its pharmacodynamic characteristics on heart rate into its components, bradycardia and tachycardia, by sulpiride. PMID- 1890612 TI - Identification and induction of cytochrome P450 2E1 in rat Kupffer cells. AB - Kupffer cells, the resident macrophages of the liver, have a well characterized role in the removal of blood-born foreign substances by phagocytosis. Because Kupffer cells may contribute to hepatic xenobiotic metabolism, the current studies evaluated the presence and inducibility of P450 2E1 in rat Kupffer cells. Hepatocytes and Kupffer cells were isolated from the livers of control and acetone-treated (1% v/v acetone in the drinking water for 7 days) rats. P450 2E1 was immunochemically detectable at low levels in Kupffer cell homogenates from untreated rats and was induced greater than 10-fold by acetone-treatment. The presence of P450 2E1 in Kupffer cells from untreated rats was confirmed by inhibition of benzene hydroxylation with anti-P450 2E1 immunoglobulin G. Benzene hydroxylase activity was induced 16.3-fold in Kupffer cells isolated from acetone treated rats and remained 70% inhibitable by anti-P450 2E1 antibody. The benzene hydroxylase activity of hepatocytes from the same animals was induced 3.9-fold by acetone treatment. The specific activity for benzene hydroxylation of Kupffer cell homogenates from acetone-treated rats was nearly equal to that for the hepatocytes from the same animals. The presence and inducibility of P450 2E1 in Kupffer cells suggests that, under conditions where P450 2E1 is induced, Kupffer cell-generated metabolites may contribute to Kupffer cell toxicity, as well as general hepatic injury. PMID- 1890613 TI - Role of protein sulfation in vasodilation induced by minoxidil sulfate, a K+ channel opener. AB - Evidence from contractile, radioisotope ion flux and electrophysiological studies suggest that minoxidil sulfate (MNXS) acts as a K+ channel opener in vascular smooth muscle. This study was designed to examine possible biochemical mechanisms by which MNXS exerts such an effect. Experiments performed in the isolated rabbit mesenteric artery (RMA) showed that MNXS, 5 microM, but not the parent compound minoxidil, was a potent vasodilator. Whereas the relaxant effects of an another K+ channel opener vasodilator, BRL-34915 (cromakalim), were removed by washing with physiological saline solution, the effects of MNXS persisted after repeated washout attempts. Furthermore, after an initial exposure of segments of intact RMA to [35S] MNXS, greater than 30% of the radiolabel was retained 2 hr after removal of the drug. In contrast, retention of radiolabel was not detected with either [3H]MNXS (label on the piperidine ring of MNXS) or [3H]minoxidil (each less than 3% after a 2-hr washout). These data suggested that the sulfate moiety from MNXS was closely associated with the vascular tissue. To determine if proteins were the acceptors of sulfate from MNXS, intact RMAs were incubated with [35S]MNXS, and then 35S-labeled proteins were separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis and analyzed by fluorography. Preferential labeling of a 116 kD protein was detected by 2 and 5 min of treatment. A 43 kD protein (resembling actin) also showed significant labeling. A similar profile of 35S-labeled proteins was observed in [35S] MNXS-treated A7r5 rat aortic smooth muscle cells, suggesting that the majority of proteins labeled by [35S]MNXS in intact RMA were components of smooth muscle cells. (ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1890614 TI - Cisapride stimulates motility of the intestine via the 5-hydroxytryptamine receptors. AB - The effects of cisapride on intestinal contractility and on release of acetylcholine (ACh) were examined using the longitudinal muscle with the myenteric plexus preparation from the guinea pig ileum, as related to the 5 hydoxytryptamine (5-HT) receptor. 5-HT exerted a dual effect, transient increase in ACh release (EC50 = 2 X 10(-6)M) via the 5-HT3 receptor, followed by inhibition (EC50 = 5 X 10(-9)M) via the 5-HT1 receptor. Cisapride at low concentrations (10(-9)M to 10(-8)M) enhanced electrical stimulation -evoked contraction and ACh release. The effect of cisapride was mimicked by methysergide and was not altered by ICS 205-930. Cisapride antagonized the 5-HT (5 X 10(-9) M) induced inhibitory effect and the IC50 of cisapride was 1.5 X 10(-9) M. These findings indicate that enhancement by low concentrations of cisapride may be due to a block of the inhibitory 5-HT1 receptor. Cisapride at medium concentrations (10(-8) M to 3 X 10(-7) M) induced enhancement of electrical stimulation-evoked twitch contractions and ACh release evoked by electrical stimulation which were antagonized by 10(-6) M ICS 205-930, while this compound antagonized the 5-HT (2 X 10(-6) M)-and 2-methyl-5-HT-induced excitatory effects, and the IC50 of cisapride was 5.2 X 10(-8) M. Thus, cisapride acts on the putative 5-HT4 receptor as an agonist and the 5-HT3 receptor as an antagonist. Cisapride at high concentrations (10(-6) M to 10(-5) M) evoked contraction and the release of ACh, and these effects were antagonized by ICS 205-930 (10(-6) M).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1890615 TI - Thapsigargin inhibits repletion of phenylephrine-sensitive intracellular Ca++ pool in vascular smooth muscles. AB - Thapsigargin (TSG), a putative selective Ca(++)-ATPase inhibitor, has been used to study Ca++ mobilization in many non-excitable cell types. This study aims to determine whether TSG is effective as a selective microsomal Ca++ uptake inhibitor by studying its ability to affect repletion of the phenylephrine (PE) sensitive Ca++ pool in rat aorta and dog mesenteric artery evaluated by contractility studies. TSG caused a concentration-dependent contraction that was dependent on the concentration of extracellular Ca++. Ca++ influx promoted by TSG was found to occur mostly through L-type Ca++ channels in the dog mesenteric artery but not in the rat aorta. When arterial rings, depleted of their PE sensitive internal store, were allowed to replete their stores in normal Krebs' solution or in the presence of elevated K+ levels, it was found that repletion was significantly enhanced in the presence of elevated K+. In TSG-treated rings, however, repletion was significantly inhibited under both conditions as indicated by the subsequent PE-induced contraction in Ca(++)-free medium. While the rate of contraction induced by elevated K+ levels was slow immediately after pool depletion in controls, it was rapid in TSG-treated arterial rings. The slow onset of K+ contraction may reflect Ca++ uptake into the pool which was absent in TSG treated arteries. Differences in the behavior of the two arteries were noted and these may reflect differences in the size of their Ca++ store and their coupling to the extracellular space. Single cells isolated from the dog mesenteric artery were also found to shorten in response to TSG to an amount comparable with that obtained from whole tissue experiments.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1890616 TI - Enhancement of in vitro mineralization in human osteoblasts by a novel prostaglandin A1 derivative TEI-3313. AB - Human osteoblasts derived from long bone periosteum were induced to mineralize in culture in the presence of 2 mM alpha-glycerophosphate, with typical characteristics of mineralization, namely, accumulation of hydroxyapatite and increases in alkaline phosphatase activity and in osteocalcin production. Mineralization was also enhanced by 10(-8) M 1 alpha, 25-dihydroxyvitamin D3. In this system, a prostaglandin A1 derivative, TEI-3313, with the chemical structure 5-[(Z,2E)-4,7-dihydroxy-2-heptenyridene]-4-hydroxy-2-methylthio-4- (4- phenoxybutyl)-2-cyclopentenone, was found to enhance mineralization as effectively as 1 alpha, 25-dihydroxyvitamin D3, although its potency was 10 times lower than that of the vitamin D3 metabolite. Osteocalcin, a bone-specific noncollagenous matrix protein, accumulated onto the cell layers by treatment with TEI-3313 to a much greater extent than those released into the culture medium. TEI-3313 also enhanced collagen synthesis. Based on the finding that TEI-3313 enhanced the synthesis of both collagen and noncollagenous protein, it is speculated that TEI-3313 enhanced the mineralization by stimulating the expression of various genes in osteoblasts. PMID- 1890617 TI - An autoradiographic analysis of cholinergic receptors in mouse brain after chronic nicotine treatment. AB - Quantitative autoradiographic procedures were used to examine the effects of chronic nicotine infusion on the number of central nervous system nicotinic cholinergic receptors. Female DBA mice were implanted with jugular cannulas and infused with saline or various doses of nicotine (0.25, 0.5, 1.0 or 2.0 mg/kg/hr) for 10 days. The animals were then sacrificed and the brains were removed and frozen in isopentane. Cryostat sections were collected and prepared for autoradiographic procedures as previously described. Nicotinic cholinergic receptors were labeled with L-[3H]nicotine or alpha-[125I]bungarotoxin; [3H]quinuclidinyl benzilate was used to measure muscarinic cholinergic receptor binding. Chronic nicotine infusion increased the number of sites labeled by [3H]nicotine in most brain areas. However, the extent of the increase in binding as well as the dose-response curves for the increase were widely different among brain regions. After the highest treatment dose, binding was increased in 67 of 86 regions measured. Septal and thalamic regions were most resistant to change. Nicotinic binding measured by alpha-[125I]bungarotoxin also increased after chronic treatment, but in a less robust fashion. At the highest treatment dose, only 26 of 80 regions were significantly changes. Muscarinic binding was not altered after chronic nicotine treatment. These data suggest that brain regions are not equivalent in the mechanisms that regulate alterations in nicotinic cholinergic receptor binding after chronic nicotine treatment. PMID- 1890618 TI - Modulation of acetylcholine release from rat striatal slices: interaction between 4-aminopyridine and atropine. AB - The objective of these studies was to determine whether the muscarinic receptor mediated autoregulation of the basal release of acetylcholine (ACh), like the modulation of evoked release, involves 4-aminopyridine (4-AP)-sensitive potassium channels. To accomplish this, striatal and hippocampal slices were incubated with 4-AP in the absence or presence of atropine, and the release of ACh was measured. 4-AP increased the release of ACh in a concentration-dependent manner; a maximal effect (280% of control release) was achieved in the presence of 100 microM. The maximal release of ACh from hippocampal slices was approximately 150% of control release and was achieved in the presence of a broad range of concentrations (33 333 microM 4-AP). Tetrodotoxin (1 microM) totally abolished the 4-AP-induced release of ACh from hippocampal slices, but only attenuated the 4-AP-induced release from striatal slices, i.e., in the presence of tetrodotoxin, the 4-AP induced release of ACh from the latter was significantly greater than control release by 54%. Atropine (0.1 microM) increased significantly the basal release of ACh from striatal slices by 61%. When striatal slices were incubated with 4-AP in the presence of this maximally effective concentration of atropine, ACh release was significantly greater than release from slices incubated with either atropine or 4-AP alone, suggesting that atropine and 4-AP increase neurotransmitter release by independent mechanisms. Although oxotremorine did not alter either the 4-AP- or atropine-induced release of ACh, it prevented the potentiated response exhibited by slices incubated with both atropine and 4 AP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1890619 TI - Dilazep potentiation of adenosine-mediated superior mesenteric arterial vasodilation. AB - The present study investigated the effects of dilazep, an inhibitor of adenosine uptake, on adenosine-mediated vasodilation in vivo. Intravenous and intraportal venous infusions of exogenous adenosine (0.04-1.0 mg/kg/min) did not recirculate to cause increases in superior mesenteric arterial conductance (SMAC) or arterial plasma adenosine levels except at the higher doses tested (0.4-1.0 mg/kg/min). After administration of dilazep, however, even low doses (0.04-0.1 mg/kg/min) of exogenous adenosine significantly increased SMAC and elevated arterial plasma adenosine concentration. The increased adenosine levels were highly correlated with the increased percentage of change of SMAC and values for Rmax and EC50 were 193.4 +/- 27.3% change of SMAC and 2.8 +/- 1.3 microM, respectively. Administration of bolus doses of 8-phenyltheophylline abolished the ability of dilazep to potentiate vasodilation, but did not affect isoproterenol-induced relaxation. Together, these results suggest that potentiation of the vasodilating effect of exogenous adenosine by dilazep is mediated through inhibition of adenosine uptake in vivo which increases the availability of plasma adenosine to act on adenosine receptors. PMID- 1890620 TI - Electrophysiological effects of cesium and tetraethylammonium in canine cardiac Purkinje fibers. AB - Cesium (Cs) and tetraethylammonium (TEA) have been shown to increase action potential duration. However, action potential duration is known to be influenced by the rate of stimulation. In this study, the effect of stimulation rate on action potential characteristics was studied in Cs-treated and TEA-loaded canine Purkinje fiber preparations. Action potentials of Purkinje fibers from Cs-treated and TEA-loaded preparations had longer durations than action potentials of Purkinje fibers from normal preparations. Greater prolongation of action potential duration was observed when the rate of stimulation was reduced in Purkinje fibers from Cs-treated and TEA-loaded preparations than those from normal preparations. Whereas the increase in action potential duration of Purkinje fibers from Cs-treated preparations was accompanied by a significant membrane depolarization, no change in membrane potential was observed in Purkinje fibers from TEA-loaded preparations. In some Cs-treated and TEA-loaded preparations, the prolonged duration observed at slow stimulation rates was associated with the appearance of early afterdepolarizations. Lidocaine and cromakalim, agents known to reduce action potential duration in normal Purkinje fibers, also shortened action potential duration in Purkinje fibers from both Cs treated and TEA-loaded preparations. However, lidocaine and cromakalim caused a significant membrane depolarization in Cs-treated Purkinje fibers but not in TEA loaded Purkinje fibers. Our results suggested that although Cs and TEA are capable of producing rate-dependent prolongation of action potential duration and the occurrence of bradycardia-dependent early afterdepolarization, differences exist in Cs-treated Purkinje fibers in terms of the appearance of membrane depolarization at reduced stimulation rate and in the presence of lidocaine and cromakalim. PMID- 1890621 TI - Age-related differences in iron-nitrilotriacetate hepatotoxicity in the guinea pig: role of copper metallothionein. AB - This study was concerned with the role of Cu and Cu-MT (metallothionein) in oxidative stress. Because hepatic Cu and Cu-MT concentrations are known to be high in the 3-day-old guinea pigs but decline to low adult levels by 7 days of life, the hepatotoxicity of ferric nitrilotriacetate (FeNTA) in the developing guinea pig was used as the experimental model in the present study. Results of this study showed that the hepatotoxic response to FeNTA (3.5 mg Fe /kg i.p.) as measured by elevation in serum aspartate aminotransferase activity, increase in lipid peroxidation, decrease in reduced glutathione/oxidized glutathione ratio and histopathological changes was higher in 3-day-old than in 7-day-old and adult guinea pigs. Furthermore, pretreatment of 7-day-old guinea pigs with cupric sulfate (0.5 mg Cu++/kg i.p.) increased hepatic Cu and Cu-MT levels and enhanced susceptibility to FeNTA. FeNTA treatment resulted in the oxidation of MT thiolates and reduction in the metal binding capacity and Cu content of MT in the 3-day-old and Cu-pretreated 7-day-old animals, providing evidence for the interaction between Cu-MT and cellular oxidants. In vitro study with FeNTA and hepatic microsomes revealed no age-related differences in microsomal lipid peroxidation; however, this parameter was stimulated in the presence of control or heat-treated cytosols isolated from 3-day-old but not those of 7-day-old animals. These observations were consistent with the involvement of Cu-MT, a heat stable metalloprotein, in the sensitization of hepatic tissues to oxidative injury in the 3-day-old animal. Moreover, in vitro study involving the use of D penicillamine, a Cu chelating agent, showed that the sensitization effect of Cu MT was mediated by Cu ions. The results of this study suggest that Cu-MT may have a prooxidative property and tissues with high Cu-MT levels may be particularly susceptible to oxidative stress. PMID- 1890622 TI - Qualitative differences in the discriminative stimulus effects of low and high doses of caffeine in the rat. AB - Caffeine engenders qualitatively different subjective effects in humans at low and high doses. Low doses of caffeine are mildly reinforcing and produce psychomotor stimulation. High doses of caffeine can produce subjective feelings of anxiety, dysphoria and depression. The present study was designed to model these different subjective states in rats using a discrete trial shock avoidance/escape drug discrimination paradigm. Rats were trained to discriminate between i.p. injections of saline and either 10 or 56 mg/kg of caffeine. Rats trained at 10 mg/kg of caffeine acquired the discrimination in an average of 93 sessions and generalized completely to a variety of xanthine and nonxanthine behavioral stimulants including: d-amphetamine, apomorphine, 7-(beta chloroethyl)theophylline, 9-chloro-2-(2-furanyl)-5,6-dihydro-1, 2,4-triazolo[1,5 c]quinazolin-5-imine (CGS 15943), cocaine, 1,7-dimethylxanthine, diethylpropion, beta-hydroxyethyltheophylline, methylphenidate, phenidimetrazine and theophylline. Rats trained at 56 mg/kg of caffeine acquired the discrimination in an average of 43 sessions and generalized completely only to theophylline. A variety of drugs representing diverse pharmacologic classifications including: benzodiazepine inverse agonists, pentylenetetrazol, yohimbine, ethylketocyclazocine and phencyclidine, were not generalized from either training dose, demonstrating the pharmacologic specificity of the discrimination. The discriminative effects of 10 mg/kg of caffeine appear to derive from a state of behavioral arousal, possibly mediated by catecholamines, and parallel the subjective effects produced by low doses of caffeine in humans. The discriminative effects of 56 mg/kg of caffeine are qualitatively different from those of 10 mg/kg but cannot be defined further at this time. PMID- 1890624 TI - Clearance and disposition of ritodrine in the fluid compartments of the fetal lamb during and after constant rate fetal intravenous infusion. AB - The disposition of the beta-2 adrenoreceptor agonist, ritodrine, has been examined in the fetal lamb during and after constant rate fetal intravenous infusion (8-24 h). Samples were collected from the fetal femoral artery, umbilical vein, maternal femoral artery, uterine vein, fetal trachea and the amniotic activity for ritodrine quantitation. The amniotic fluid was also analyzed for conjugated metabolites of ritodrine. Ritodrine appears to be cleared across the sheep placenta only to a limited extent (placental clearance 9.2 +/- 2 ml/min/kg; mean +/- S.E.M.). There is, however, significant fetal nonplacental clearance of ritodrine (fetal nonplacental clearance 52.8 +/- 8.0 ml/min/kg). At least part of this clearance appears to be due to fetal drug metabolism, as evidenced by the accumulation of glucuronide conjugates of ritodrine in the amniotic fluid. Ritodrine was also shown to accumulate in the amniotic and fetal tracheal fluids and persist after fetal arterial plasma ritodrine concentrations became undetectable. The accumulation of ritodrine in the tracheal fluid may be of pharmacologic significance, given the well documented, potent effects of beta 2 agonists on fetal lung function and development. PMID- 1890623 TI - Repeated cocaine administration causes persistent enhancement of D1 dopamine receptor sensitivity within the rat nucleus accumbens. AB - The rewarding effects of cocaine are mediated primarily by the mesoaccumbens dopamine (DA) system, which projects from A10 DA cell bodies within the ventral tegmental area to the nucleus accumbens (NAc). This pathway is also intricately involved in the locomotor stimulating effect of cocaine and the progressive increases (sensitization) in this behavior observed after repeated administration of cocaine and other psychomotor stimulants. By using single-cell electrophysiological recording and microiontophoretic techniques, we demonstrated previously that repeated cocaine administration (10 mg/kg i.p., twice daily, 14 days) renders impulse-regulating somatodendritic A10 DA autoreceptors subsensitive, thereby increasing impulse flow within the mesoaccumbens DA system. In striking contrast, inhibitory responses of NAc neurons to iontophoretic DA were significantly increased in cocaine-treated rats tested 16 to 24 hr after the last cocaine injection. In the present study, iontophoretic application of selective D1 (SKF 38393) and D2 (quinpirole) DA receptor agonists was utilized to determine the extent to which each of these DA receptor subtypes is altered by repeated cocaine administration. After 2 weeks of twice daily cocaine (10 mg/kg i.p.) injections, significant increases in the inhibitory responses of NAc neurons to SKF 38393, but not quinpirole, were observed. In addition, this D1 receptor sensitization was still evident when animals were tested either 7 days or 1 month after the final cocaine injection. After 2 months of withdrawal from cocaine treatment, D1 receptor sensitivity in the NAc had returned to control levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1890625 TI - Behavioral effects of D1 and D2 dopamine receptor antagonists in squirrel monkeys. AB - The behavioral effects of dopamine antagonists differing in affinity and selectivity at D1 and D2 dopamine receptors were compared in squirrel monkeys responding under a fixed-interval schedule of stimulus-shock termination. D1 selective antagonists included (R)-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5 phenyl-1H-3-benzazepine-7 -ol, SCH 23390; its enantiomer (S)-(+)-8-chloro-2,3,4,5 tetrahydro-3-methyl-5-phenyl-1H-3-benzazepine-7 -ol, SCH 23388; [(-)-trans 6,7,7a,8,9,13b-hexahydro-3-chloro-2-hydroxy-N-methyl-5H - benzo(d)naphtho-(2,1 b)azepine], SCH 39166; (R)-7-bromo-8-hydroxyl-3-methyl-1-phenyl-2,3,4,5 tetrahydro-1H-3-benzaze pine, R-SKF 83566; (R)-2,3,4,5-tetrahydro-3-methyl-5 phenyl-1H-3-benzazepine-7-ol, R-SKF 83692; 2,3,4,5-tetrahydro-3-methyl-5-phenyl 1H-3-benzazepine-7-ol, RS-SKF 83692. D2-selective antagonists included cis-N-(1 benzyl-2-methylpyrrolidine-3-yl)-5-chloro-2-methoxy-4- methylaminobenzamide, YM 09151-2, eticlopride, raclopride, haloperidol, risperidone, remoxipride, S sulpiride and R-sulpiride; nonselective dopamine antagonists were S-butaclamol and chlorpromazine. Regardless of selectivity for D1 or D2 receptors, all drugs produced dose-related decreases in fixed-interval responding. A high degree of stereoselectivity was evident for both D1 antagonists (SCH 23390 and R-SKF 83692 more potent than, respectively, SCH 23388 and RS-SKF 83692) and D2 antagonists (S sulpiride more potent than R-sulpiride). High doses of the D1 and D2 antagonists also reduced motor activity and impaired coordination in monkeys in the home cage after test sessions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1890626 TI - Effects of different cardiac steroids on intracellular sodium, inotropy and toxicity in sheep Purkinje fibers. AB - The purpose of the present study was to examine the differences between cardiac steroids that might underlie the variations in toxic/therapeutic ratios that have been reported to occur in vitro as well as in vivo. We used Na(+)-sensitive microelectrodes to measure changes in intracellular Na+ activity (aiNa) associated with positive inotropic and toxic effects of acetylstrophanthidin (AS) and a semisynthetic agent, actodigin. Measurements of aiNa, twitch tension and transmembrane potential were made in sheep Purkinje fibers stimulated at 0.03, 1 and 2 Hz. Ca(+)+i overload toxicity was indicated by the presence of transient depolarizations (TD). The following results were obtained: 1) at a stimulation frequency of 1 Hz, aiNa was significantly higher at peak tension with AS (13.6 +/ 1.1 mM) than with actodigin (11.0 +/- 0.4 mM, P less than .01), yet TD occurred at the same aiNa (10.9 +/- 0.7 vs. 11.9 +/- 0.7 mM, respectively, N.S.); 2) at frequencies of 1 to 2 Hz, aiNa was lower when TD occurred (10.4 +/- 0.9 mM at 2 Hz) than at peak tension (12.1 +/- 0.8 mM, P less than .05) during exposure to AS, whereas aiNa was the same at peak tension (10.6 +/- 1.1 mM) and when TD occurred (10.5 +/- 1.1 mM, N.S.) during exposure to actodigin; 3) the degree of positive inotropy at a high stimulation frequency (2 Hz) was significantly greater with actodigin (about 12-fold increase in force compared to control) than with AS (about 6-fold increase in force).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1890627 TI - Transport of monocarboxylic acids at the blood-brain barrier: studies with monolayers of primary cultured bovine brain capillary endothelial cells. AB - The kinetics and mechanism of the transport of monocarboxylic acids (MCAs) were studied by using primary cultured bovine brain capillary endothelial cells. Concentration-dependent uptake of acetic acid was observed, and the kinetic parameters were estimated as follows: the Michaelis constant, Kt, was 3.41 +/- 1.87 mM, the maximum uptake rate, Jmax, was 144.7 +/- 55.7 nmol/mg of protein/min and the nonsaturable first-order rate constant, Kd, was 6.66 +/- 1.98 microliters/mg of protein/min. At medium pH below 7.0, the uptake rate of [3H]acetic acid increased markedly with decreasing medium pH, whereas pH independent uptake was observed in the presence of 10 mM acetic acid. An energy requirement for [3H]acetic acid uptake was also demonstrated, because metabolic inhibitors (2,4-dinitrophenol and rotenone) reduced significantly the uptake rate (P less than .05). Carbonylcyanide-p-trifluoro-methoxyphenylhydrazone, a protonophore, inhibited significantly the uptake of [3H]acetic acid at medium pH of 5.0 and 6.0, whereas 4,4'-diisothiocyanostilben-2,2'-disulfonic acid did not. Several MCAs inhibited significantly the uptake rate of [3H]acetic acid, whereas di- and tricarboxylic acids did not. The uptake of [3H]acetic acid was competitively inhibited by salicylic acid, with an inhibition constant, Ki, of 3.60 mM, suggesting a common transport system between acetic acid and salicylic acid. Moreover, at the medium pH of 7.4, salicylic acid and valproic acid inhibited significantly the uptake of [3H]acetic acid, demonstrating that the transport of MCA drugs could also be ascribed to the MCA transport system at the physiologic pH.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1890628 TI - Binding profiles of class I antiarrhythmic agents to cardiac muscarinic receptors: competitive and allosteric interactions with the receptors and their pharmacological significance. AB - The binding profiles of the class I antiarrhythmic agents disopyramide, pirmenol and pentisomide (CM7857) to cardiac muscarinic receptors were characterized by the binding assay using [3H]-N-methyl scopolamine ([3H]NMS) as a ligand and their anti-muscarinic actions were investigated functionally in left atrial preparations. All the agents displaced the specific binding of 200 pM [3H]NMS from guinea pig left atrial membranes. Computer-assisted analysis indicated that pirmenol interacted with a single class of binding sites, but the displacement curves of disopyramide and pentisomide were shallow and best fitted to a two-site model. When the concentration of [3H]NMS was increased to 1 nM, the displacement curve of pirmenol was best fitted to a two-site model. In higher concentrations, these agents inhibited the dissociation of [3H]NMS initiated by 1 microM atropine in a concentration-dependent manner, thus revealing allosteric interactions. Two enantiomers of pirmenol possessed qualitatively the same binding properties as the racemate. In guinea pig left atria, disopyramide, pirmenol and pentisomide shifted the concentration-response curves for the negative inotropic effect of carbachol in a parallel manner. The slopes of Schild plot were not significantly different from unity, indicating that they act as a competitive antagonist of cardiac muscarinic receptors. Excellent correlation between the high affinity pKi values and the pA2 values was established for the antiarrhythmic agents. These findings suggest that disopyramide, pirmenol and pentisomide all interact with cardiac muscarinic receptors in both a competitive fashion and an allosteric one. The dual mode of the interaction with cardiac muscarinic receptors seems to be independent of their chiralities.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1890629 TI - Agonist and antagonist properties of serotonergic compounds in pigeons trained to discriminate either quipazine or L-5-hydroxytryptophan. AB - The serotonin (5-HT) receptor-related compounds metergoline, pirenperone, ketanserin, cyproheptadine, pizotyline, methysergide, lysergic acid diethylamide, mianserin and cinanserin were studied in pigeons trained to discriminate l-5 hydroxytryptophan (l-5-HTP) (18.0 mg/kg) from saline and in pigeons trained to discriminate quipazine (1.0 mg/kg) from saline. Metergoline did not generalize to either quipazine or l-5-HTP but did antagonize drug-appropriate responding in both groups. Ketanserin potently blocked the quipazine discriminative stimulus and neither generalized to nor attenuated the l-5-HTP discriminative stimulus. Pirenperone, cinanserin, cyproheptadine, methylsergide, pizotyline and mianserin attenuated the quipazine discriminative stimulus at low doses and, at higher doses, generalized to the l-5-HTP discriminative stimulus. No antagonism of the l 5-HTP-discriminative stimulus or generalization to the quipazine-discriminative stimulus were observed with these compounds. A correlation coefficient of 0.93 was calculated between the potencies of 5-HT compounds to generalize to the l-5 HTP stimulus and the binding affinities of these compounds for a 5-HT1 receptor in rat brain. In addition, a correlation coefficient of 0.78 was calculated between the potencies of 5-HT compounds to attenuate the quipazine stimulus and the binding affinities of these compounds for the 5-HT2 receptor in rat brain. These observations suggest cyproheptadine, pizotyline, methysergide, lysergic acid diethylamide, mianserin and cinanserin are agonists at the 5-HT1 receptor in the l-5-HTP discrimination and antagonists at a 5-HT2 receptor in the quipazine discrimination in pigeons. PMID- 1890630 TI - Inhibition of caudal medullary expiratory neurones by retrofacial inspiratory neurones in the cat. AB - 1. Comparisons between the spike discharge of inspiratory neurons within the retrofacial area (RFN), and the membrane potential of expiratory neurones within the caudal medulla were made in pentobarbitone-anaesthetized, vagotomized, artificially ventilated cats. Spike-triggered averaging (STA) of synaptic potentials, triggered by the discharge of inspiratory RFN neurones, was utilized to test for synaptic connectivity. 2. Eighty-nine neurons with respiratory-phased discharge patterns were recorded in the vicinity of the RFN. Fifty-four neurones discharged at or slightly before the onset of the inspiratory burst activity of the phrenic nerve and continued firing throughout inspiration. Two continued to fire during post-inspiration. Forty-five of fifty-four inspiratory RFN neurones exhibited incrementing discharge patterns, six discharged with a plateau pattern, while only three neurones had a decrementing discharge pattern. 3. The membrane potential trajectories of caudal expiratory neurones revealed a typical wave of early inspiratory hyperpolarization. Occasionally, a second wave of hyperpolarization occurred during late inspiration, in conjunction with increased phrenic nerve activity. 4. Spike-triggered averaging revealed averaged inhibitory postsynaptic potentials (IPSPs), indicative of inhibitory synaptic connections, between eight and sixty-three pairs of RFN inspiratory and caudal expiratory neurones. 5. Inhibitory postsynaptic potentials detected by STA exhibited a relatively long latency and a slow time course. The IPSPs began, on average, 3.8 ms after an RFN action potential. The rise times, half-widths and durations of IPSPs were longer than expected for a monosynaptic somal input from myelinated axons of inspiratory RFN neurones. It is suggested that an inhibitory relay neurone in the immediate vicinity of the expiratory neurones is activated by a collateral of the RFN inspiratory neurone. 6. Retrofacial inspiratory neurones were antidromically activated only when high-intensity electrical stimulation was applied in the vicinity of caudal expiratory neurones. 7. The averaged IPSPs were preceded by diphasic and triphasic 'spike potentials'. The averaged spike potentials were highly entrained to the action potentials of RFN inspiratory neurones which triggered IPSPs. The spike potentials may be terminal potentials recorded from axons of RFN inspiratory neurones. 8. Evidence for convergence of synaptic inputs was obtained from STA tests in a caudal expiratory neurone receiving IPSPs from four RFN neurones. 9. The functional significance of this observation is discussed. We conclude that RFN inspiratory neurones exert a moderate inhibitory influence and act conjointly with other types of medullary inspiratory neurones. PMID- 1890631 TI - Differentiation of sympathetic neurones projecting in the hypogastric nerves in terms of their discharge patterns in cats. AB - 1. Sympathetic neurones that project in the hypogastric nerves (HGNs) were analysed for their discharge patterns in anaesthetized cats. The activity of these neurones was recorded from their axons. Afferents from the pelvic organs (urinary bladder, colon, anal canal), and arterial baro-and chemoreceptors were stimulated. 150 postganglionic and nine preganglionic neurones were analysed. 2. The postganglionic neurones exhibited reflex patterns that were typical of visceral vasoconstrictor neurones and various types of motility-regulating neurones. Most motility-regulating neurones and all visceral vasoconstrictor neurones had ongoing activity. 3. Postganglionic motility-regulating neurones were not influenced by stimulation of arterial baro-and chemoreceptors, but showed distinctive reflexes on stimulation of afferents from pelvic organs. Three subgroups of motility-regulating neurones were identified: type 1 neurones (34% of the sample of postganglionic neurones) were excited from the urinary bladder and inhibited or not influenced from the colon. Type 2 neurones (14%) exhibited a reflex pattern reciprocal to that of the type 1 neurones. Anal motility regulating neurones (8%) were only influenced from the anal canal. The most powerful reflexes in these types of motility-regulating neurones were elicited by mechanical stimulation of the anal mucosa. 4. Postganglionic visceral vasoconstrictor neurones (16% of the sample) were under powerful inhibitory control from the arterial baroreceptors and weakly excited by stimulation of arterial chemoreceptors. Visceral stimuli had little or no effect on most of these neurones. Some visceral vasoconstrictor neurones exhibited some overlap in their functional properties with motility-regulating neurones. 5. Twenty-eight per cent of our sample of postganglionic neurones showed no reflexes to the afferent stimuli used. About half of these neurones had on-going activity. 6. Nine preganglionic neurones with on-going activity were identified. Most of these neurones behaved like visceral vasoconstrictor or motility-regulating neurones. 7. This study shows that the majority of postganglionic neurones that project in the HGNs can be divided into the same functional types as the lumbar preganglionic neurones that project to the inferior mesenteric ganglion. The proportions of the different types of neurones are similar at pre- and postganglionic levels. Thus the centrally generated patterns of activity are most likely faithfully transmitted from the spinal cord to the target organs in the pelvic cavity in functionally separate pathways. PMID- 1890632 TI - The effects of opiates on the respiratory activity of thoracic motoneurones in the anaesthetized and decerebrate rabbit. AB - 1. Efferent discharges were recorded from inspiratory and expiratory intercostal nerve filaments (T2-T10) in artificially ventilated, anaesthetized or decerebrate rabbits with or without vagotomy. 2. Hypocapnic apnoea was used to study the fractional end-tidal CO2 (FET,CO2)-dependent tonic discharges of the expiratory motoneurones, the FET,CO2 threshold for rhythm generation and the FET,CO2 response curve of both inspiratory and expiratory burst activity. 3. Incremental doses of morphine (e.g. 1 mg kg-1 I.V.) produced slowing of the respiratory rhythm due to prolongation of the expiratory duration and an elevation of the FET,CO2 threshold for rhythm generation. Eventually apnoea supervened with associated tonic firing of the expiratory motoneurones. At the elevated levels of FET,CO2 bursts of inspiratory activity, with concomitant phasic inhibition of the tonic expiratory activity, could occur either spontaneously or following sensory stimulation. The peak integrated activities of these bursts were closely similar to the values obtained for corresponding levels of FET,CO2 before the administration of morphine. 4. Tonic expiratory activity responded to increased levels of FET,CO2, as it had during hypocapnic apnoea prior to morphine, by an increased discharge frequency of single units or recruitment of new units. 5. All of these effects of morphine were immediately reversed by naloxone (100 micrograms kg-1). 6. Naloxone (greater than 100 micrograms kg-1), without pre treatment with morphine, led to an increase in respiratory frequency due to a shortening of the expiratory duration and a dose-dependent reduction in the FET,CO2 threshold for rhythm generation. There was little alteration either in the inspiratory response to FET,CO2 during rhythm or in the FET,CO2 response of the expiratory output whether expressed as tonic activity during hypocapnic apnoea or phasic activity following the onset of rhythm. 7. Thus opiates act upon the mechanisms of rhythm generation without depressing the FET,CO2 drive as expressed either as phasic or tonic activation of the motoneurones. PMID- 1890633 TI - On the mechanism of nucleotide diphosphate activation of the ATP-sensitive K+ channel in ventricular cell of guinea-pig. AB - 1. Effects of intracellular nucleotide diphosphates (NDPs) on the ATP-sensitive K+ channel (K+ATP channel) were examined in ventricular cells of guinea-pig heart, using the inside-out patch clamp technique. On formation of inside-out patches in the ATP-free internal solution, the K+ATP channel appeared and then ran down spontaneously. This run-down of the K+ATP channel activity was probably due to dephosphorylation. 2. Millimolar concentrations of various NDPs, e.g. UDP (uridine diphosphate), IDP (inosine diphosphate), CDP (cytidine diphosphate) and GDP (guanosine diphosphate), applied to the internal side of the patch membrane, induced openings of the K+ATP channel after run-down, i.e. in the dephosphorylated state. ADP opened the channel weakly at low concentrations (100 microM) but inhibited it at higher concentrations (1-10 mM). 3. NDP-induced openings of the channel were Mg2+ dependent and inhibited by ATP (100 microM) and glibenclamide (1 microM). None of nucleosides, nucleotide monophosphates nor nucleotide triphosphates induced openings of the channel. Thus, the K+ATP channel may have a Mg(2+)-dependent NDP-binding site, which induces openings of the dephosphorylated channel in ATP-free solution, in addition to the Mg(2+) independent ATP-binding inactivation site and phosphorylation site. 4. In inside out patches, pinacidil (a K+ATP channel opener) activated the K+ATP channel in the phosphorylated state but not in the dephosphorylated state. In the presence of NDPs (UDP, IDP, CDP, GDP), however, pinacidil (30 microM) enhanced openings of the dephosphorylated K+ATP channel prominently. 5. From the above results, we concluded that NDP-binding to the specific site has similar effects to channel phosphorylation, i.e. it keeps the K+ATP channel in an operative state in ATP free solution and enhances the pinacidil-induced channel openings. PMID- 1890634 TI - Energy metabolism in human slow and fast twitch fibres during prolonged cycle exercise. AB - 1. The effects of prolonged exercise on energy metabolism in type I and type II muscle fibres in the vastus lateralis muscle were investigated in six male subjects (20.0 +/- 0.5 years, mean +/- S.E.M.) who performed one-legged cycling at 61% of maximum O2 consumption (VO2,max; determined with one leg) until fatigue or for a maximum of 2 h. 2. Analysis of pools of freeze-dried fibres obtained by needle biopsy and separated into specific types by the myofibrillar ATPase histochemical procedure indicated higher (P less than 0.05) lactate concentrations in type II fibres compared to type I fibres at 15 min (43.9 +/- 9.7 and 51.2 +/- 9.8 mmol (kg dry wt)-1) and at 60 min (18.2 +/- 4.7 and 25.9 +/- 6.5 mmol (kg dry wt)-1). No differences existed in lactate concentration between fibre types for pre-exercise (10.0 +/- 1.6 and 13.3 +/- 2.8 mmol (kg dry wt)-1) or post-exercise. 3. Glycogen degradation was most pronounced in type I fibres. By the end of exercise, glycogen concentration was 82.4 +/- 45 mmol glucosyl units (kg dry wt)-1 in type I fibres and 175 +/- 62 mmol glucosyl units (kg dry wt)-1 in type II fibres. 4. No significant changes in ATP and creatine phosphate (CrP) were found in either fibre type with exercise. 5. It is concluded that, at least for lactate and glycogen, fibre-specific differences are evident in prolonged submaximal exercise. The cause of the difference probably relates both to the unique energy metabolic characteristics of each fibre type and to the manner in which they are utilized during the exercise. 6. The failure to find a reduction in ATP concentration in either fibre type during prolonged exercise in the face of a progressive increase in the number of fibres showing little or no glycogen concentration suggests that protective mechanisms exist that prevent an energy crisis. The nature of these protective mechanisms remains to be elucidated. PMID- 1890635 TI - Reciprocal Ia inhibition between elbow flexors and extensors in the human. AB - 1. Reciprocal inhibition between elbow flexor and extensor muscles (biceps and triceps brachii) has been investigated in nine healthy subjects. Two techniques were used to assess changes in motoneurone excitability after stimulation of antagonist muscle afferents: (1) monosynaptic reflexes elicited by a mechanical stimulation of the distal muscle tendon (tendon tap); (2) post-stimulus time histograms (PSTH) of voluntarily activated motor units. 2. Electrical stimulation of the antagonist muscle nerve produced a short-latency and short-lasting inhibition of the flexor and extensor motoneurones. The amount of this inhibition was found to be similar in both motor nuclei. 3. The inhibition could be evoked with conditioning electrical stimuli as low as 0.7 x motor threshold (MT) or by very weak tendon taps applied to the antagonist tendon. In the former case the threshold of this inhibition was found to be consistently increased after raising the threshold of Ia afferent fibres by a long-lasting muscle vibration. Since a contribution from cutaneous afferent fibres was ruled out, it is concluded that this inhibition was Ia in origin. 4. Post-stimulus time histograms of voluntarily activated triceps and biceps motor units were made following electrical stimulation of homonymous and antagonist muscle afferents. This enabled an estimate of the central synaptic delay of the inhibitory process. An average central delay of 0.94 ms in excess of that of monosynaptic facilitation was found, thus suggesting that the inhibitory process could be mediated by only one interneurone. 5. A conditioning reflex discharge elicited in the antagonist muscle by a tendon tap depressed or suppressed this inhibition. This depression was maximal when the reflex discharge was elicited 10-20 ms before the conditioning stimulus for the inhibition and never lasted more than 30 ms. It is argued that the only mechanism compatible with such a depression is the inhibitory activity of Renshaw cells acting on the pathway mediating reciprocal inhibition. 6. We conclude that group Ia afferent fibres from elbow extensor and flexor muscles project monosynaptically onto Ia inhibitory interneurones to mediate disynaptic reciprocal inhibition of antagonist motoneurones. PMID- 1890637 TI - Respiratory-associated rhythmic firing of midbrain neurones in cats: relation to level of respiratory drive. AB - 1. We recorded phrenic nerve activities and single unit firing of mesencephalic neurones in unanaesthetized supracollicularly decerebrated, paralysed and ventilated cats, in which vagi and carotid sinus nerves had been ablated. We made these measurements first at low levels of respiratory drive associated with normal PCO2 levels, then with increased respiratory drive and levels of phrenic activity produced by hypercapnia or by carotid sinus nerve stimulation. 2. We found that at least a quarter of the neurones in the central tegmental field of the mesencephalon, which were irregularly tonic or silent at low respiratory drives, developed a rhythmic increase of firing associated with each respiration. There appeared to be a threshold at about 50% of maximum respiratory activity, below which the respiratory-associated rhythm did not occur. Above this level, neuronal firing increased in graded fashion with increasing magnitude of respiratory activity. The latency from onset of phrenic activity to onset of increased neuronal firing was quite long (1.0 s) at drives just above the threshold but shortened to as little as 0.3 s as drive increased towards its maximum. 3. Cutting the spinal cord at C1-C2 had no effect on the ability of increased respiratory activity to generate a respiratory-associated rhythm in mesencephalic neurones. 4. Short-lasting anaesthesia with the agent Saffan caused mesencephalic neurones to lose the respiratory-associated rhythm with little change in phrenic activity and no change in respiratory cycle timing. 5. We also found a mesencephalic response to ventilator-induced chest expansion. The latency of the response from onset of expansion, indexed by fall of airway PCO2, to onset of neurone firing was shorter (0.2 s) than that found with the respiratory associated rhythm. In seventeen neurones we found both the respiratory-associated rhythm and the independent ventilator-associated rhythm. 6. We interpret our findings to show that the respiratory-associated rhythmic firing of midbrain neurones is not primarily involved in generation or modulation of the motor function of the respiratory oscillator. We believe, instead, that these neurones are part of a sensory pathway conveying information about the magnitude of central neural respiratory drive, as well as spinally transmitted information from receptors in the chest wall, to thalamus and cortex. We suggest that the sensation ultimately generated may be that of 'air hunger' or dyspnoea. PMID- 1890636 TI - Dynamic control of muscle stiffness and H reflex modulation during hopping and jumping in man. AB - 1. The objective of the study was to evaluate the functional effects of reflexes on muscle mechanics during natural voluntary movements. The excitability of the H (Hoffmann) reflex was used as a measure of the excitability of the central component of the stretch reflex. 2. We recorded EMG, ground reaction forces and the H reflex in the soleus muscle in humans while landing from a downward jump, during drop jumping and during hopping. The movements were also recorded by high speed cinematography. 3. The EMG pattern was adapted to the motor task. When landing the EMG in the soleus muscle and in the anterior tibial muscle showed preinnervation and alternating activity after touch down. When hopping there was little preinnervation in the soleus muscle, and the activity was initiated about 45 ms after touch down by a peak and continued unbroken until lift off. In the drop jumps the EMG pattern depended on the jumping style used by the subject. 4. The H reflex in the soleus muscle was strongly modulated in a manner appropriate to the requirements of the motor task. During landing from a downward jump the H reflex was low at touch down whereas while hopping it was high at touch down. During drop jumping it was variable and influenced by the jumping technique. 5. Muscle stiffness in the ankle joint was negative after touch down when landing, but always positive when hopping. 6. It is suggested that during landing the alternating EMG pattern after touch down was programmed and little influenced by reflexes. During hopping reflexes could contribute to the initial peak and the EMG during lift off. 7. The programmed EMG activity and the suppression of the H reflex while landing probably contribute to the development of the negative stiffness and change the muscles from a spring to a damping unit. PMID- 1890638 TI - Atropine-resistant submandibular responses to stimulation of the parasympathetic innervation in the anaesthetized ferret. AB - 1. Submandibular salivary and vascular responses to stimulation of the peripheral end of the chorda-lingual nerve at 20 Hz continuously for 60 min were investigated in anaesthetized ferrets, in which the sympathetic innervation to the gland was cut, in the presence and absence of atropine (2.0 mg kg-1). 2. Both the increase in submandibular salivary flow and protein output, which occurred in response to nerve stimulation, were substantially reduced following the administration of atropine, the latency was greatly increased thereby, and both responses were more transient but neither was abolished by atropine. The fall in submandibular vascular resistance was not significantly affected by atropine, either in respect of extent or duration. 3. Chorda-lingual stimulation produced an increase in the output of vasoactive intestinal peptide (VIP), substance P (SP) and calcitonin gene-related peptide (CGRP) in the submandibular venous effluent blood. Each of these responses was maximal within the first 10 min after the onset of stimulation and declined thereafter. The time-scales of both the CGRP and SP responses were similar to those of the atropine-resistant secretory responses, both being quite short-lived, whereas the output of VIP (like the atropine-resistant vascular response) was significantly greater than the basal value throughout the whole of the 60 min period of stimulation. 4. The CGRP response was completely abolished by pre-treatment with atropine, whereas the outputs of both VIP and SP were significantly enhanced thereby. Both the submandibular vascular and secretory responses to chorda-lingual stimulation were almost completely suppressed following the administration of hexamethonium, and there was then no detectable release of peptidergic agonists from the gland. 5. The atropine-resistant submandibular salivary secretory responses were completely abolished by pre-treatment with a tachykinin inhibitor [( D-Arg1, D-Cl2 Phe5, Asn6, D-Trp7,9, Nle11]-SP; 0.75 mg kg-1) without affecting the fall in submandibular vascular resistance. 6. Following pre-treatment with hexamethonium, I.V. bolus injections of methacholine, SP and CGRP elicited increases in submandibular blood flow and secretion of saliva. VIP caused an increase in blood flow without overt secretion, although it is known to increase secretion of protein and to potentiate the secretory response to SP. Taken together, all these results are consistent with the contention that VIP contributes to the vasodilator response to stimulation of the para-sympathetic innervation in this gland and that both SP and CGRP are likely to contribute to the secretory response. PMID- 1890639 TI - Diastolic, systolic and sarcoplasmic reticulum [Ca2+] during inotropic interventions in isolated rat myocytes. AB - 1. The fluorescent indicator Fura-2 has been used to monitor intracellular [Ca2+] (Ca2+i) in myocytes isolated from the ventricles of rat hearts. 2. The relationships between diastolic Ca2+i, systolic Ca2+i and the Ca2+ content of the sarcoplasmic reticulum (SR; assayed using caffeine) have been studied during changes of stimulation rate and bathing [Ca2+] (Ca2+o). 3. When stimulation rate was increased, there were increases in diastolic Ca2+i, systolic Ca2+i and the Ca2+ content of the SR. 4. The SR inhibitor ryanodine (1 mumol l-1) decreased the size of the Ca2+i transient, and abolished the increase of Ca2+i produced by caffeine (10 mmol l-1). In the presence of ryanodine, increasing stimulation rate increased diastolic Ca2+i but not systolic Ca2+i. 5. Increasing Ca2+o led to increases of diastolic Ca2+i, systolic Ca2+i and SR Ca2+ content similar to those observed during changes in stimulation rate. 6. Ryanodine altered the relationship between systolic and diastolic Ca2+i during changes of Ca2+o. 7. These results are consistent with a change of diastolic Ca2+i leading to an increase in the Ca2+ content of the SR, and hence an increase in the size of the Ca2+i transient during changes in stimulation rate and Ca2+o. PMID- 1890640 TI - Lithium clearance: modification by the loop of Henle in man. AB - 1. The contribution of Li+ reabsorption in the loop of Henle to lithium clearance (CLi) and the possible mechanism(s) involved were assessed in healthy volunteers. Four mechanisms were considered: (a) passive reabsorption in the thin ascending limb, (b) solvent drag in the thin descending limb, (c) the Na+, K+, 2Cl- transporter in the thick ascending limb and (d) paracellular movement in the thick ascending limb. 2. Since alterations in the corticomedullary osmolal concentration gradient produced by fluid restriction (500 ml day-1) and subsequent water loading (15 ml kg-1) did not affect either CLi (28.5 +/- 2.1 vs. 28.2 +/- 1.9 ml min-1) or fractional lithium clearance (FELi; 23.5 +/- 2.0 vs. 23.0 +/- 1.9%), it is unlikely that substantial Li+ reabsorption occurs in the thin limbs by either passive movement or solvent drag. 3. Increasing plasma Li+ with unchanged plasma Na+ in salt-replete volunteers was associated with only small reductions in CLi (32.8 +/- 1.3 ml min-1, P less than 0.05) and FELi (27.3 +/- 1.8 vs. 25.3 +/- 2.0%, P less than 0.05). This suggests that substantial Li+ reabsorption on the Na+, K+, 2Cl- transporter does not occur. 4. Bumetanide increased FELi in salt-depleted (LS) and salt-replete (HS) volunteers and abolished the pre-diuretic difference in FELi between salt intakes (LS, 16.6 +/- 1.5 vs. 38.7 +/- 2.3%, P less than 0.001; HS, 30.1 +/- 1.5 vs. 40.5 +/- 2.0%, P less than 0.001). Changes in CPO4 and CHCO3 were not detected. Acetazolamide produced comparable increases in FELi (LS, 16.6 +/- 1.5 vs. 38.7 +/- 2.2%, P less than 0.001; HS, 30.1 +/- 1.5 vs. 43.1 +/- 2.4%, P less than 0.01); and CPO4 and CHCO3 were increased. When tubular flow to the loop of Henle was increased by acetazolamide, the bumetanide-induced increases in FELi were reduced (LS, 38.7 +/ 2.2 vs. 48.7 +/- 2.3%, P less than 0.001; HS, 43.1 +/- 2.4 vs. 48.1 +/- 2.6%, P less than 0.001). 5. These data are consistent with the view that (a) Li+ is reabsorbed by a bumetanide-sensitive mechanism in the loop of Henle, (b) approximately 20 and 10% of the filtered load, respectively, is reabsorbed in the loop in salt-depleted and salt-replete volunteers, (c) flow-dependent, voltage driven paracellular movement in the thick ascending limb is the likely mechanism and (d) this mechanism could account for the difference in Li+ reabsorption between low and high salt intakes. PMID- 1890641 TI - Neurohumoral mechanisms and the role of arterial baroreceptors in the reno vascular response to haemorrhage in rabbits. AB - 1. Conscious rabbits, with implanted renal artery Doppler flow probes were bled at a constant rate (4 ml min-1). We assessed the contribution of autonomic, hormonal and local factors to the renal vasoconstrictor response to 20% loss of blood volume (BV) and the role of the sinoaortic baroreceptors in the neurohumoral response. 2. With intact autonomic effectors, 20% BV loss was associated with a small fall in vascular conductance, which was completely unaffected by inhibition or blockade of the combined effects of the two major pressor hormones angiotensin II (AII) and arginine vasopressin (AVP). Combined blockade of the autonomic effects plus those of the two pressor hormones resulted in marked elevation of vascular conductance, considered to be due to the local effects of haemorrhage. This response provided the baseline for assessing the constrictor response in the intact animal which, during 20% BV loss, was entirely due to reflex activity through the sympatho-adrenal system. 3. In contrast to the early phase of haemorrhage (less than 20% BV removal) both hormones played a role in the maintenance of mean arterial pressure immediately after haemorrhage and in the maintenance of renal vascular tone. This suggested that the contribution by hormones occurs only after more pronounced blood loss and hypotension. 4. In the presence of autonomic blockade with mecamylamine plus methscopolamine (plus a constant infusion of noradrenaline to maintain resting blood pressure) the renal vasoconstrictor response was similar to that of the intact animal. We have previously found that this regime is associated with greatly enhanced release of AVP and plasma renin activity. Sinoaortic denervation had no effect on this hormonally mediated vasoconstriction. 5. When the autonomic nervous system was intact but the effects of AII and AVP were blocked to prevent the accentuated hormonally mediated vasoconstriction, sinoaortic denervation completely abolished the normal autonomic renal constrictor response, which is thus largely under control of the arterial baroreceptors. PMID- 1890643 TI - Actions of n-alcohols on nicotinic acetylcholine receptor channels in cultured rat myotubes. AB - 1. The actions of the n-alcohols from pentanol to dodecanol on nicotinic acetylcholine receptor (nAChR) channels were investigated by recording single ACh activated channel activity from inside-out membrane patches isolated from cultured rat myotubes. Alcohols were applied to the cytoplasmic side of the membrane; aqueous concentrations ranged from 11.7 mM-pentanol to 0.02 mM dodecanol. 2. The intermediate-chain alcohols (pentanol to octanol) caused channel currents to fluctuate between the fully open and closed state level so that openings occurred in bursts interrupted by brief gaps. Closed time distributions were fitted well with two exponential components, the fast component representing the closures within a burst. The number of gaps within a burst was dependent on alcohol concentration whereas gap duration was independent of concentration but increased with increasing chain length of the alcohol up to octanol. 3. Nonanol and decanol reduced the mean duration of bursts of openings but did not cause an increase in the number of short closed intervals within a burst. Beyond decanol there was a decline in the ability of the n-alcohols to affect channel function. A saturated solution of undecanol (0.07 mM) reduced the mean open time by 33 +/- 17%, whereas a saturated solution of dodecanol had no significant effect. 4. The current integral per burst was reduced by all the n alcohols between pentanol and undecanol. The IC50S were as follows: hexanol, 0.53 +/- 0.14 mM; heptanol, 0.097 +/- 0.02 mM; octanol, 0.04 mM and nonanol, 0.16 +/- 0.035 mM. 5. The results were analysed in terms of an open channel block model with a long-lived closed-blocked state beyond the blocked state. Over the range of concentrations tested this describes the effects of all the n-alcohols (C5 to C12) on channel gating reasonably well. 6. Blocking rate constants (k+B) for pentanol through to nonanol were calculated to be between 2.8 and 5.7 X 10(6) M-1 S-1. These values are based on the assumption that the concentration of the alcohols at their site(s) of action was equal to the aqueous concentration applied to the membrane. 7. Equilibrium dissociation constants (KD), calculated from the blocking and unblocking rate constants (KD = k-B/k+B), decreased with increasing chain length from 8 mM for pentanol to 0.15 mM for octanol. The standard free energy per methylene group for adsorption to the site of action was calculated to be about -3.3 kJ mol-1.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1890642 TI - Effects of sulphydryl modification on skinned rat skeletal muscle fibres using 5,5'-dithiobis(2-nitrobenzoic acid). AB - 1. The sulphydryl groups of skinned skeletal muscle fibres have been reacted with 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB) in order to determine whether the effects of modifications to the contractile proteins are reflected in changes in the physiological properties of the contractile apparatus and Ca(2+)-regulatory system. 2. Results obtained from fast-twitch and slow-twitch rat fibres which were treated with DTNB (10 mM, pH 8.6, 5 degrees C) for various periods of time under relaxing conditions showed that a major effect of the modification was to reduce the level of maximally Ca(2+)-activated force and fibre stiffness. Force and fibre stiffness were found to decline in proportion. Treatment with DTNB under these conditions did not cause a rise in force or fibre stiffness in relaxed fibres of either type. 3. The effects induced by DTNB under relaxing conditions were substantially reversed by exposure to the reducing agent dithiothreitol (DTT) (10 mM, pH 7.1, 23 degrees C). Force abolished by 30-35 s treatment with DTNB recovered after subsequent DTT treatment to 67 +/- 3% (mean +/- S.E.M., n = 4) in fast-twitch fibres and to 91 +/- 2% (n = 7) in slow-twitch fibres. These results were significantly different (t test, P less than 0.001) indicating that the level of force recovery depended upon the fibre type. 4. DTNB was found to affect not only the maximal Ca(2+)-activated force, but also the force-pCa (pCa = -log10[Ca2+]) relationships of the fibres in a complex, fibre type specific way. DTT treatment partially reversed these DTNB effects. 5. The skinned fibre preparations reacted differently with DTNB under rigor conditions than under relaxing conditions, indicating that rigor modifies the reactivity of the functional sulphydryl groups to the thiol-targeted agents. 6. When superprecipitation assays (an in vitro analogue of fibre contraction) were carried out with recombined myofibrillar proteins which had been previously reacted with DTNB it was found that modification of myosin, but not modification of thin filament proteins, led to changes in the superprecipitation reaction. 7. Both the skinned fibre results and the superprecipitation results indicate that the effects of DTNB upon the fibre characteristics are primarily due to modifications of the sulphydryl groups of myosin. Therefore, these results show that myosin is not only involved in determining the ability of the contractile apparatus to develop force but also in determining the Ca(2+)-regulatory characteristics of the muscle fibre. PMID- 1890644 TI - Tonic interocular suppression and binocular summation in human vision. AB - 1. Spatial sensitivity of human foveal vision was examined using sinusoidally modulated gratings. Our primary concern was the influence of interocular light adaptation upon monocular visibility. 2. Interocular adapting influences depend upon spatial frequency and adapting luminance. Interocular adaptation has a negligible influence upon the sensitivity to 1 cycle/deg gratings. Any visible interocular adapting field improves the sensitivity to intermediate spatial frequencies (2-5 cycles/deg). 3. Brighter interocular backgrounds (greater than 0.1 cd/m2) improve sensitivity to higher spatial frequencies (10-20 cycles/deg). 4. The interocular adapting influences summarized in (2) and (3) above cannot be duplicated by monocular or binocular adaptation. Similarly, monocular or binocular adaptation have negligible influences upon binocular visibility. 5. The interocular adapting effect summarized in (3) above can be duplicated by pressure blinding the contralateral eye. We conclude that monocular spatial sensitivity is subject to a tonic interocular suppression (TIS) from the dark-adapted eye. 6. The spatial sensitivity resulting from binocular viewing is nearly identical to that observed by combining monocular viewing with interocular light adaptation. We suggest that the improvement in sensitivity resulting from two-eyed viewing may be attributable to the removal of TIS instead of to binocular physiological summation. PMID- 1890645 TI - Reflex actions of one proprioceptor on the motoneurones of a muscle receptor and their central modulation in the shore crab. AB - 1. Reflex efferent control of a muscle stretch receptor by a joint proprioceptor of the same limb was studied in an isolated CNS preparation from the shore crab. The influence of 'fictive locomotor' activity on this interjoint reflex was also examined. 2. The thoracic-coxal muscle receptor organ (TCMRO) and the coxo-basal chordotonal organ (CBCO), which monitor movement and position of the first and second joints of the posterior leg, were isolated together with the whole thoracic ganglion complex. The TCMRO, functionally analogous to a mammalian muscle spindle, has two receptor motoneurones. RM1 innervating the receptor muscle alone and RM2 which also supplies the 'extrafusal' promotor muscle. The CBCO is a typical arthropod elastic strand organ, with many sensory neurones but lacking an efferent supply. The TCMRO was fixed at its mid-length, and stretch hold-release stimuli were applied to the CBCO. Efferent activity was recorded from the cut nerve roots of the four basal limb muscles and intracellularly as excitatory junction potentials (EJPs) from the receptor muscle. 3. A dynamic increase in the frequency of action potentials in RM1 occurred on both stretch and release of the CBCO. During the hold phase the RM1 activity declined from the dynamic response but remained elevated compared to the resting tonic discharge. RM2, identified by EJPs occurring 1:1 with a unit in the promoter nerve, responded in a similar way. 4. One or more promotor motoneurones were usually co activated with the two receptor efferents in response to input from the CBCO. In a typical example the average spike frequency of RM1 rose from 0 to 27 Hz during the dynamic phases (stretch and release) of the CBCO stimulus, falling to 2.5 Hz during the hold phase, while the corresponding promotor spike frequencies were 25 and 7.5 Hz, respectively. The other three muscle nerves recorded from generally also showed reflex driving by the CBCO. 5. The totally isolated thoracic ganglion could produce a rhythmic, bursting motor output in the absence of any sensory input. During this centrally generated activity the receptor motor innervation was strongly co-activated with the promotor bursts, and the reflex input from the CBCO was overridden or modulated in a phase-dependent manner. 6. The proximally directed interjoint reflex to the receptor muscle probably functions to maintain the tension on the sensory endings of the TCMRO, and so enable them to respond effectively at all times to movements of the basal leg joint.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1890646 TI - The effects of metabolism on Na(+)-K(+)-Cl- co-transport in ferret red cells. AB - 1. The effects of altering metabolism on Na(+)-K(+)-Cl- co-transport were studied in ferret red cells. Na(+)-K(+)-Cl- co-transport was measured as the bumetanide sensitive uptake of 86Rb. 2. Glucose, but not inosine or adenosine, sustained metabolism and maintained cell ATP content ([ATP]i) at the physiological level. [ATP]i could be reduced by prolonged incubation of cells in a substrate-free medium or more quickly by incubating cells with 2-deoxyglucose or with a mixture of iodoacetamide and glucose. 3. Na(+)-K(+)-Cl- co-transport activity was inhibited when [ATP]i was reduced to below 100 mumol (1 cell)-1 by starvation or by treatment with 2-deoxyglucose. However, a unique relationship between [ATP]i and activity could not be found. [ATP]i and the method and time course of ATP depletion all influenced activity. The inhibition of Na(+)-K(+)-Cl- co-transport, caused by reducing [ATP]i could be partially reversed by restoring [ATP]i to normal. 4. Increasing the concentration of intracellular ionized magnesium [( Mg2+]i) did not stimulate co-transport activity in ATP-depleted cells. This contrasts with the substantial stimulation seen in cells with normal [ATP]i. 5. Vanadate stimulated Na(+)-K(+)-Cl- co-transport activity in ATP-depleted cells but not in cells with normal [ATP]i. Fluoride did not affect activity at any [ATP]i. 6. The effects of some sulphydryl reagents on Na(+)-K(+)-Cl- co-transport were also examined. n-Ethylmaleimide (1 mM) inhibited Na(+)-K(+)-Cl- co-transport while it stimulated bumetanide-resistant potassium transport. Dithiothreitol (1 mM) did not affect activity. Iodoacetamide (6 mM) appeared to reduce the inhibition of cotransport activity seen at low [ATP]i but also greatly increased cell fragility. 7. The data suggest that activity of the Na(+)-K(+)-Cl- co transport system is controlled by a cycle of phosphorylation and dephosphorylation with the phosphorylated form being active. Phosphorylation and transport appear to be almost maximal in ferret red cells with normal [ATP]i. Reduction of [ATP]i may allow changes in phosphatase activity to manifest as changes in transport rate. Differences in the balance between phosphorylation and dephosphorylation may explain tissue-dependent variations in the response of the system to various stimuli. PMID- 1890647 TI - Spontaneous and noradrenaline-induced transient depolarizations in the smooth muscle of guinea-pig mesenteric vein. AB - 1. Recordings of membrane current were made in the smooth muscle of short segments of mesenteric vein before or during stimulation with noradrenaline (NA). 2. Small veins (diameter less than 150 microns) when cut into short segments (of length less than 250 microns) had the passive electrical characteristics of short cables both before and during activation with NA. 3. Spontaneous transient depolarizations (STDs) or the underlying inward currents (STICs) were recorded in these preparations. STDs were of myogenic origin as they were not blocked by tetrodotoxin or antagonists to the alpha-adrenoreceptor and persisted after either denervation or disruption of the endothelium. 4. STDs had time courses similar to the underlying currents and were generally slow compared to the membrane time constant of the short segments. 5. STDs and the underlying currents showed large variability in frequency and amplitude both within and between short segments. Currents were typically less than 0.3 nA, were characteristic in shape, had half-durations normally in the range 0.1-0.7 s and reversed at about -25 mV. 6. STDs persisted, but at markedly reduced frequencies, after exposure (3-10 min) to a solution in which cobalt ions had been used to substitute for Ca2+. STDs were also substantially suppressed by exposure to low-chloride solution. 7. Caffeine induced excitatory and inhibitory conductances. An initial component of the caffeine-induced responses showed similar voltage dependence to STDs and was also suppressed by exposure to low-chloride solution. 8. NA, through activation of alpha-adrenoreceptors, caused a sustained depolarization or inward current (under voltage clamp) with considerable membrane potential or current noise often in the form of agonist-induced spontaneous transient depolarizations (ASTDs) or currents (ASTICs). There were marked increases in amplitude and frequency of ASTDs with increase in NA concentrations. 9. ASTDs appeared to be generated within the smooth muscle as they were activated in preparations which had been denervated or in which the endothelium had been disrupted. 10. Except for the pathway of activation, ASTDs were indistinguishable from STDs having half durations in the same range (0.1-2 s with the majority less than 0.7 s). The underlying currents again showed large variation in amplitude (typically less than 0.3 nA; maximum recorded 0.9 nA). They reversed at about -25 mV, could still be elicited in cobalt solution (but at reduced intensity for long exposures to this low-Ca2+ solution) and were reduced by long term exposure to low-chloride solution.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1890648 TI - GTP and noradrenaline-induced force in isolated toxin-permeabilized rat anococcygeus and guinea-pig portal vein. AB - 1. Strips of smooth muscle from rat anococcygeus and guinea-pig portal vein were treated with solutions containing crude alpha-toxin from the bacterium Staphylococcus aureus. This rendered the surface membrane permeable to small molecular weight substances, but left functional sarcolemmal adrenoceptors. Tension measurements from these preparations were used to investigate the effects of guanosine-5'-triphosphate (GTP) on the noradrenaline-induced Ca2+ release from the sarcoplasmic reticulum (SR) of the smooth muscle of rat anococcygeus and guinea-pig portal vein. 2. Under conditions of low Ca2+ buffering (0.2 mM-EGTA), applying a maximal dose of noradrenaline (30 microM) to a toxin-permeabilized strip of anococcygeus muscle and longitudinal muscle of guinea-pig portal vein caused a transient contracture. Subsequent exposures to noradrenaline resulted in progressively smaller contractures. However, the rate of decline in the size of the noradrenaline-induced contracture was greater in rat anococcygeus muscle than in guinea-pig portal vein preparations. The decline in the size of the contracture in toxin-permeabilized anococcygeus muscle was not due to a fall in the Ca2+ content of the SR or a reduced Ca2+ release from the SR in response to myo-inositol 1,4,5-trisphosphate (IP3). 3. The tension transients due to noradrenaline were enhanced and maintained in the presence of 100 microM-GTP in toxin-permeabilized guinea-pig portal vein. Addition of 100 microM-GTP caused a transient contracture in permeabilized rat anococcygeus muscle and only promoted the next noradrenaline response, thereafter the amplitude of the contractures decayed to zero. 4. Addition of guanosine-5'-O-(2 thiodiphosphate) (GDP-beta-S, 100 microM) would be expected to cause a reversible reduction of the noradrenaline response by binding to the intermediary G-protein. This was observed in toxin-permeabilized portal vein, but in rat anococcygeus muscle, GDP beta-S caused slowing of the response to noradrenaline, thereafter the response to noradrenaline was absent. The noradrenaline response did not recover when GDP beta-S was removed. 5. The non-metabolizable form of GTP, guanosine-5'-O-(3 thiotriphosphate) (GTP-gamma-S, 100 microM), caused a transient contracture in both toxin-permeabilized rat anococcygeus muscle and guinea-pig portal vein. In both these tissues, the addition of GTP-gamma-S resulted in the irreversible inhibition of the response to noradrenaline. 6. In the presence of a high concentration (10 mM) of the Ca2+ buffer EGTA, GTP (100 microM) and noradrenaline (30 microM) increased Ca(2+)-activated force in both tissues.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1890649 TI - Adaptation of glucose transport across rat enterocyte basolateral membrane in response to altered dietary carbohydrate intake. AB - 1. The effect of changes in the carbohydrate content of the diet on D-glucose transport across the basolateral membrane of rat enterocytes has been compared with alterations in transport across the brush-border membrane. 2. Measurement of carrier-mediated D-glucose uptake across the jejunal brush border from animals fed a low- or high-carbohydrate diet showed a change in the maximal rate of transport by 7 days which was maintained for 14 days. The low-carbohydrate diet produced a progressive decline in uptake whereas the high-carbohydrate diet increased the transport. There was no alteration in the apparent affinity constant as a result of the dietary manipulations and no discernible trend for changes in the passive permeability to glucose. 3. Transport of D-glucose across the basolateral membrane was also affected by the dietary composition. After 7 days the maximal transport rate was greater in the animals fed the high carbohydrate diet. However, while this increase was maintained for 14 days, uptake into vesicles prepared after 2 weeks on the low-carbohydrate diet showed a return to control levels. 4. A detailed analysis of the time course of these responses showed the effect on basolateral membrane transport to be inducible within 3 days of switching from the low- to the high-carbohydrate diet and could be reversed within a similar period. 5. Kinetic studies using purified basolateral membrane vesicles confirmed that the change in transport was the result of an increase in the maximal transport rate. Analysis of cytochalasin B binding to these membranes showed a parallel change in the number of glucose inhibitable binding sites. 6. The component of the diet responsible for these changes was further investigated by replacing the glucose in the high carbohydrate food with galactose, fructose, mannose or 3-O-methylglucose. Only glucose and fructose produced any significant change in the transport across the basolateral membrane. 7. It is concluded that in response to changes in the carbohydrate content of the diet there are alterations in the capacity for glucose transport across the basolateral membrane of the enterocyte as well as in the brush-border membrane. The change in transport across the basolateral membrane is best explained by an increase in the number of glucose carriers in this membrane. PMID- 1890650 TI - Comparative nasal effects of bradykinin, kallidin and [Des-Arg9]-bradykinin in atopic rhinitic and normal volunteers. AB - 1. The structure-activity relationship of kinins within the nose has been investigated in atopic rhinitic (n = 7) and non-rhinitic (n = 7) subjects. On 4 separate days, each separated by a week, subjects randomly underwent nasal challenge with incremental doses of either the B1 agonist [Des-Arg9]-bradykinin, the B2 agonists kallidin or bradykinin, or vehicle placebo in a double-blind comparative study. The nasal response was monitored objectively by measurement of nasal airways resistance (NAR) by active posterior rhinomanometry and subjectively by symptom reporting of nasal blockage, rhinorrhoea, nasal itch and nasal pain. 2. The B2 agonists kallidin and bradykinin both induced a dose dependent increase in NAR (P less than 0.001) and were associated with symptomatic reporting of nasal blockage (P less than 0.05), rhinorrhoea (P less than 0.01) and nasal discomfort (P less than 0.05) compared to placebo. In contrast the effects of the B1 agonist [Des-Arg9]-bradykinin on NAR and symptom reporting were indistinguishable from placebo. No difference could be identified in the nasal response to kallidin and bradykinin between rhinitic and non rhinitic subjects and there was no evidence of B1 receptor upregulation in the disease state. For the whole group the provocative dose of agonist inducing a 50% increase in NAR (PD50) was 1.77 x 10(-4) mol for bradykinin and 2.86 x 10(-4) mol for kallidin (P greater than 0.05). 3. These findings identify that the nasal effects of kinins are mediated through B2 receptors and the advent of B2 receptor antagonists will permit a further evaluation of the role of kinins in rhinitis. PMID- 1890652 TI - In mice, the muscle weakness due to age is absent during stretching. AB - 1. The contractile force was compared in isolated soleus muscles from young (2.5 8 months old) and aged (28-31 months old) mice. Force was measured at 25 degrees C during isometric tetanic contractions during isovelocity stretching and shortening contractions. 2. The normalized isometric force was lower by 13.3% in muscles from aged mice. Muscles from young and aged mice produced 0.951 +/- 0.031 N mg-1 (n = 12) and 0.824 +/- 0.048 N mg-1 (n = 9) respectively. The relaxation time, from 90 to 10% of the tetanic force, of muscles from aged mice was 102.1 +/ 3.7 ms (n = 6), which was longer than that for muscles from young mice, 84.4 +/- 3.8 ms (n = 6) (means +/- S.E.M.). 3. The force during shortening was also reduced in muscles from aged animals by the same proportion as the isometric force. Therefore the force during shortening relative to the isometric force was the same in muscles from young and aged mice. 4. During rapid stretching soleus muscles from aged mice produced a similar force to those from young mice. Therefore stretch can remove the weakness in muscles of aged mice. 5. These changes in muscles from aged mice are similar to those produced when inorganic phosphate (Pi) levels are raised, in skinned rabbit psoas fibres, or during fatigue or with low intracellular pH (pHi), in frog muscle. It is possible therefore that the force loss due to ageing may be due to a higher Pi level or a lower pHi. PMID- 1890651 TI - Inhibition of Ca(2+)-activated K+ currents by intracellular acidosis in isolated type I cells of the neonatal rat carotid body. AB - 1. K+ and Ca2+ currents were recorded from enzymatically isolated type I cells of the neonatal rat carotid body, using the whole-cell configuration of the patch clamp technique. The effects of intracellular acidosis, caused by bath application of anions of weak acids (propionate and acetate), were tested on these currents. 2. Bath application of propionate or acetate (10 or 20 mM) caused reversible reductions in K+ current amplitudes. These effects were maximal at low, positive test potentials where a shoulder in the current-voltage relationship occurs due to the activation of Ca(2+)-activated K+ currents. 3. Time-course studies showed propionate to cause a rapid initial reduction of K+ currents which recovered partially during its continued application. Removal of propionate produced small, transient overshoots of K+ current amplitudes. In the absence of propionate or acetate, bath application of the Na(+)-H+ exchange inhibitor amiloride caused slowly developing inhibition of K+ current amplitudes. 4. Changing extracellular pH from 7.4 to 8.0 increased K+ current amplitudes, but at this pHo propionate caused smaller reductions in K+ currents than at a pHo of 7.4. 5. In the presence of 0.1 mM-Cd2+, or in high-Mg2+ (6 mM), low-Ca2+ (0.1 mM) solutions, the residual, Ca(2+)-independent K+ currents were unaffected by 20 mM propionate or acetate. 6. Ca2+ channel currents were also recorded, using 10 mM Ba2+ as the charge carrier. These sustained currents were completely abolished by 0.1 mM-Cd2+ and were enlarged in the presence of 5 microM-Bay K 8644, suggesting that the currents passed through L-type Ca2+ channels. 7. Ca2+ channel currents were not significantly affected by intracellular acidosis caused by bath application of 10 mM-propionate or acetate. They were also unaffected by a reduction of the extracellular pH from 7.4 to 7.0. 8. It is concluded that intracellular acidosis selectively inhibits Ca(2+)-activated K+ currents in type I carotid body cells. The possible significance of this effect on chemotransduction in the intact carotid body is discussed. PMID- 1890653 TI - A motor programme for the initiation of forward-oriented movements in humans. AB - 1. The EMG sequence activated before the initiation of a number of fast forward oriented voluntary movements was analysed quantitatively in normal subjects. 2. The sequence consisted of an initial inhibitory component directed to the soleus motor nucleus, followed by a second excitatory one directed to the tibialis anterior (TA). 3. The spectrum of functional utilization included motor tasks in which the prime movers are leg and thigh muscles (initiation of gait, rising on tip-toes), thigh and trunk muscles (fast-forward bending of the trunk, standing up) and upper-limb muscles (forward throw or catch). 4. In a same motor task and across the different motor tasks, performed at various speeds, the latency of soleus inhibition and TA activation with respect to the onset of movement co varied according to a linear function, indicating a close temporal correlation between the two components. 5. In all the movements investigated, the earliest mechanical effect was a backward displacement of the centre of foot pressure in the sagittal plane. 6. Soleus inhibition alone and TA burst alone were each able to produce a backward displacement of the centre of foot pressure, but the effect was significantly slower after soleus inhibition. 7. The spatio-temporal parameters of the sequence were modulated according to the pre-existing postural conditions. For the gait initiation protocol, increasing initial forward leaning led to a decrease in the amplitude of soleus inhibition and the TA burst, and to a change in their relative time delays. Modulation was different on the two sides. We could define a postural boundary as the degree of forward leaning beyond which the full sequence is no longer called into action. 8. The spatio temporal parameters of the sequence were pre-set according to the requirements of the forthcoming movement. In the gait initiation protocol, the amplitude and synchronization of the TA burst were directly correlated with velocity of movement, while the relative delay between soleus inhibition and TA activation was inversely correlated. Modulation on the two sides differed. We could define a velocity boundary as the velocity of movement below which the full sequence is no longer called into action. 9. We suggest that the EMG sequence described can be considered a motor programme that, through direct action on the position of the centre of foot pressure (the variable primarily controlled), will precisely adjust the configuration of forces external to the body, allowing the contraction of the prime mover(s) to interact appropriately with them for the production of a specific, forward-oriented movement. PMID- 1890654 TI - Force-velocity relations and myosin heavy chain isoform compositions of skinned fibres from rat skeletal muscle. AB - 1. This study was performed to assess whether muscle contractile properties are related to the presence of specific myosin heavy chain (MHC) isoforms. 2. Force velocity relations and MHC isoform composition were determined in seventy-four single skinned muscle fibres from rat soleus, extensor digitorum longus and plantaris muscles. 3. Four groups of fibres were identified according to their MHC isoform composition determined by monoclonal antibodies: type 1 (slow), and types 2A, 2B and 2X (fast). 4. With respect to maximum velocity of shortening (V0), the fibres formed a continuum between 0.35 and 2.84 L/s (muscle lengths per second) at 12 degrees C. V0 in type 1 fibres (slow fibres) was between 0.35 and 0.95 L/s (0.639 +/- 0.038 L/s; mean +/- S.E. of mean). V0 in type 2 fibres (fast fibres) was consistently higher than 0.91 L/s. Ranges of V0 in the three fast fibre types mostly overlapped. Type 2A and 2X fibres had similar mean V0 values (1.396 +/- 0.084 and 1.451 +/- 0.066 L/s respectively); type 2B fibres showed a higher mean V0 value (1.800 +/- 0.109 L/s) than type 2A and 2X fibres. 5. Mean values of a/P0, an index of the curvature of force-velocity relations, allowed us to identify two groups of fibres: a high curvature group comprised of type 1 (mean a/P0, 0.066 +/- 0.007) and 2A (0.066 +/- 0.024) fibres and a low curvature group comprised of type 2B (0.113 +/- 0.013) and 2X (0.132 +/- 0.008) fibres. 6. Maximal power output was lower in slow fibres than in fast fibres, and among fast fibres it was lower in type 2A fibres than in type 2X and 2B. 7. Force per unit cross-sectional area was less in slow fibres than in fast fibres. There was no relation between fibre type and cross-sectional area. 8. The results suggest that MHC composition is just one of the determinants of shortening velocity and of other muscle contractile properties. PMID- 1890655 TI - A slow calcium-dependent chloride current in rhythmic hyperpolarization in neurones of the rabbit vesical pelvic ganglia. AB - 1. Voltage-clamp recordings were made from neurones of vesical pelvic ganglia isolated from the rabbit urinary bladder. A rhythmic outward current, ISH, which corresponds to the spontaneous hyperpolarization, occurred at fairly constant intervals in fifty-eight of eighty-four neurones superfused with Krebs solution. The peak amplitude of the ISH was 0.5 +/- 0.2 nA (n = 48; mean +/- S.E.M.). 2. The ISH was eliminated in a Krebs solution containing nominally zero calcium and 12 mM-magnesium. Lowering the temperature of the superfusing solution from 36 to 22 degrees C also inhibited the occurrence of the ISH. 3. Bath application of caffeine increased the frequency of ISH. In contrast, ryanodine and procaine reversibly blocked ISH. 4. In thirty-four of fifty-eight neurones, the ISH was composed of two current components, an initial fast ISH with duration of 1-10 s and a slow ISH lasting 15-60 s. In the remaining twenty-four neurones, ISH showed only the fast component. 5. The fast ISH was associated with an increased membrane conductance and the slow ISH was associated with a decreased membrane conductance. The reversal potentials of the fast and the slow ISH were -88 +/- 7 mV (n = 4) and -30 +/- 6 mV (n = 4), respectively. 6. Tetraethylammonium (5 mM) and barium (1 mM) blocked the fast ISH but not the slow ISH. Intracellular caesium injected by ionophoresis through a Cs(+)-filled microelectrode blocked the fast ISH, without affecting the slow ISH. Apamin and (+)-tubocurarine selectively suppressed the fast component of the ISH. 7. Substitution of isethionate (67 mM) for chloride increased the amplitude of the slow ISH and shifted the reversal potential of the slow ISH to +1 +/- 8 mV (n = 5). A slow ISH with amplitude of 0.1-1 nA and was still observed in a low-sodium (26.2 mM) solution. The stilbene derivative, 4-acetamido-4'-isothiocyanostilbene-2,2' disulphonic acid (SITS), a chloride channel blocker, suppressed the slow ISH. 8. These results suggest that ISH is composed of two distinct calcium-dependent currents, a fast ISH produced by activation of potassium conductance and a slow ISH produced by inactivation of chloride conductance. 9. The after hyperpolarization (AHP) following the action potential was also composed of apamin-sensitive and insensitive spontaneous hyperpolarizing oscillations. The apamin-insensitive component of IAHP was increased by lowering external chloride activity, while it was depressed by SITS. PMID- 1890656 TI - Ontogenic development of lamb intestinal sodium-glucose co-transporter is regulated by diet. AB - 1. The ontogenic development of the intestinal Na(+)-glucose co-transporter was measured in lambs as a function of diet. Transport activity was assayed in brush border membrane vesicles and the expression of transport protein in the brush border membrane determined by Western analysis. 2. Na(+)-dependent D-glucose transport increased to a maximum (300-700 pmol mg-1 s-1) within the first 2 weeks of birth and then declined to negligible amounts (less than 10 pmol mg-1 s-1) over the next 8 weeks. There was no further change over the next 2-3 years. Early changes were associated with modifications in both the maximum velocity Vmax for transport and expression of carrier protein in the brush-border plasma membrane. 3. Maintaining lambs on a milk replacer diet beyond the normal weaning period prevented the normal decline in the expression of Na(+)-glucose co-transport. At 5 weeks the transport rate was 433 +/- 150 pmol mg-1 s-1 in lambs maintained on milk replacer, but only 79 +/- 40 pmol mg-1 s-1 in normally reared control lambs. 4. Infusing the proximal intestine of 2- to 3-year-old sheep with 30 mM-D-glucose for four days increased the rate of transport 40- to 80-fold above that found in control animals perfused with mannitol. A similar but smaller increase was observed in one animal perfused with the non-metabolizable sugar alpha-methyl-D glucopyranoside. The induced increase in glucose transport was correlated with the expression of the co-transporter protein in the brush-border plasma membrane. 5. It is concluded that the age-related decline in Na(+)-glucose co-transport in the sheep intestine is directly due to the decrease in D-glucose (and D galactose) reaching the small intestine after development of the rumen. These results further suggest that luminal sugar substrates for the co-transporter promote both the maintenance and the up-regulation of the brush-border transport protein and it is the intact sugar itself which controls gene expression during enterocyte maturation. PMID- 1890657 TI - Excitation by irritant chemical substances of sensory afferent units in the cat's cornea. AB - 1. Single-unit electrical activity was recorded from thin myelinated sensory nerve fibres innervating the cornea of deeply anaesthetized cats. 2. Based on their responses to mechanical (calibrated von Frey hairs), chemical (10 mM-acetic acid and/or 616 mM-NaCl) and thermal (ice-cold or heat up to 51 degrees C) stimuli, corneal A delta fibres were classified as polymodal nociceptors (63%), high-threshold mechanoceptors (22%) and mechano-heat nociceptors (15%). Thin myelinated fibres responding only to cold were found in the limbus of the eye. 3. Application of 10 mM-acetic acid on the corneal surface for 30 s evoked in polymodal fibres a brisk discharge of impulses often followed by a low-frequency impulse activity. NaCl (616 mM) produced a more gradual and sustained firing response. 4. The responses of polymodal fibres to acid were proportional to extracellular pH values (pH range: 4.5-6.0). After sensitization to repeated heating, most mechano-heat units developed a sensitivity to acidic stimulation. 5. Topical 0.33 mM-capsaicin excited polymodal nociceptors of the cornea; 5 min after capsaicin about 15% of these fibres were inactivated to all subsequent stimuli. In the rest of the fibres, chemical and thermal sensitivity disappeared after 0.33-3.3 mM-capsaicin, but mechanosensitivity was preserved. 6. Corneal mechanoceptors and limbal cold receptors were not affected by capsaicin (up to 33 mM). 7. These experiments demonstrate that the cornea of the cat is innervated by polymodal as well as mechanoceptive A delta nociceptors. In polymodal nociceptive fibres, mechanical and chemical sensitivities appear to be subserved by separate transduction mechanisms. PMID- 1890658 TI - Measurement of work done by ATP-induced sliding between rabbit muscle myosin and algal cell actin cables in vitro. AB - 1. The basic properties of the ATP-dependent actin-myosin interaction responsible for muscle contraction were studied using an in vitro force-movement assay system, in which a glass microneedle coated with rabbit skeletal muscle myosin was made to slide on the actin filament arrays (actin cables) in the internodal cell of an alga Nitellopsis obtusa with ionophoretic application of ATP. 2. In response to an ATP current pulse (intensity, 5-85 nA; duration, 0.5-10 s), the myosin-coated needle moved for a distance and eventually stopped, indicating reformation of rigor actin-myosin linkages to prevent elastic recoil of the bent needle. A subsequent ATP current pulse again produced the needle movement starting from the baseline force attained by the preceding needle movement. 3. With a constant amount of ATP application, the amount of work done by the ATP induced actin-myosin sliding first increased with increasing baseline force from zero to 0.4-0.6P0, and then decreased with further increasing baseline force, thus giving a bell-shaped work versus baseline force relation. 4. With increasing amount of ATP application, the amount of work done by the actin-myosin sliding increased more steeply as the baseline force was increased from zero to 0.4 0.6P0. 5. These results are discussed in connection with the basic properties of the actin-myosin sliding in muscle contraction. PMID- 1890659 TI - Effect of frusemide on lithium clearance and proximal tubular reabsorption in anaesthetized rats. AB - 1. In order to investigate the lithiuretic effect of frusemide, simultaneous measurements of fractional lithium excretion (FELi) and fractional fluid delivery to the end of the proximal convoluted tubules were made in Inactin-anaesthetized rats, first during a control period, then during intravenous infusion of frusemide at either 0.8 or 8.0 mg kg-1 h-1. Fluid balance was maintained by infusion of NaCl-KCl solution adjusted to match urinary excretion rates; measurements were made after urine flow had stabilized. 2. In time-control animals, which did not receive frusemide, no significant changes were observed in either FELi or fractional fluid delivery to the end of the proximal convoluted tubules (determined as the plasma/tubular fluid inulin concentration ratio, P/TFIn). 3. In animals given the high dose of frusemide, FELi increased from 0.22 +/- 0.02 (mean +/- S.E.M.) during the control period to 0.45 +/- 0.03 during frusemide infusion (P less than 0.001); this was accompanied by a modest increase in P/TFIn, from 0.43 +/- 0.02 to 0.51 +/- 0.02 (P less than 0.01). 4. In animals given the lower dose of frusemide, FELi increased from 0.21 +/- 0.01 to 0.37 +/- 0.01 (P less than 0.001). In this group, however, there was no discernible change in P/TFIn (0.43 +/- 0.02 vs. 0.44 +/- 0.01, not significant). 5. These results suggest that under control conditions a significant component of lithium reabsorption may occur beyond the proximal tubule, most likely in the loop of Henle. PMID- 1890660 TI - The two power limits conditioning step frequency in human running. AB - 1. At high running speeds, the step frequency becomes lower than the apparent natural frequency of the body's bouncing system. This is due to a relative increase of the vertical component of the muscular push and requires a greater power to maintain the motion of the centre of gravity, Wext. However, the reduction of the step frequency leads to a decrease of the power to accelerate the limbs relatively to the centre of gravity, Wint, and, possibly, of the total power Wtot = Wext + Wint. 2. In this study we measured Wext using a force platform, Wint by motion picture analysis, and calculated Wtot during human running at six given speeds (from 5 to 21 km h-1) maintained with different step frequencies dictated by a metronome. The power was calculated by dividing the positive work done at each step by the duration of the step (step-average power) and by the duration of the positive work phase (push-average power). 3. Also in running, as in walking, a change of the step frequency at a given speed has opposite effects on Wext, which decreases with increasing step frequency, and Wint, which increases with frequency; in addition, a step frequency exists at which Wtot reaches a minimum. However, the frequency for a minimum of Wtot decreases with speed in running, whereas it increases with speed in walking. This is true for both the step-average and the push-average powers. 4. The frequency minimizing the step-average power equals the freely chosen step frequency at about 13 km h-1: it is higher at lower speeds and lower at higher speeds. The frequency minimizing the push-average power approaches the freely chosen step frequency at high speeds (around 22 km h-1 for our subjects). 5. It is concluded that the increase of the vertical push does reduce the step-average power, but that a limit is set by the increase of the push-average power. Between 13 and 22 km h-1 the freely chosen step frequency is intermediate between a frequency minimizing the step-average power, eventually limited by the maximum oxygen intake (aerobic power), and a frequency minimizing the push-average power, set free by the muscle immediately during contraction (anaerobic power). The first need prevails at the lower speed, the second at the higher speed. PMID- 1890661 TI - Reversibility of snuff dippers' lesion in Swedish moist snuff users: a clinical and histologic follow-up study. AB - The purpose of this study was to assess possible reversibility of oral mucosal changes, associated with the use of Swedish moist snuff, after change of habit. Biopsies from a total material of 252 regular snuff users, 184 using loose snuff and 68 using portion-bag packed snuff, were screened microscopically to identify histopathologic epithelial changes in addition to, or differing from, those generally seen as a result of snuff use. The main basis for selection of these variables were the criteria of epithelial dysplasia as defined by WHO and the eight histologic features, which have been reported to be the most important discriminators to separate cases with leukoplakia that subsequently developed carcinoma, from those that did not. Twenty-nine subjects, 3 showing Degree 2 lesions, 21 Degree 3 lesions and 5 Degree 4 lesions, all of them loose snuff users were identified. All the 29 users were re-examined clinically and histologically after 3-6 months. The rebiopsy was always secured from the same mucosal area as the original biopsy. At follow-up, 20 subjects had either stopped their snuff habit or changed to portion-bags and changed placement of the quid. All of them showed a healthy mucosa at the previous biopsy site and normal tissue in the histologic examination of the rebiopsies. Seven subjects had changed to portion-bags and variably reduced their daily exposure to snuff. At follow-up they presented with less pronounced clinical changes and the rebiopsies showed evidence of reduced epithelial changes. One major conclusion from this study is that tissue changes, clinically as well as histologically, are reversible following cessation of snuff habit.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1890662 TI - Serum cytokine levels in patients with oral mucous membrane disorders. AB - Serum cytokine levels were examined in 18 oral squamous cell carcinoma (SCC), 26 lichen planus (OLP), 20 recurrent aphthous stomatitis (RAS), 8 herpetic gingivostomatitis (HGS), 16 pseudomembrane candidiasis (PMC) and 19 acute bacterial infection (ABI) cases. All SCC and most PMC patients possessed clear serum IL-3. No clear increase of IL-4 was observed in most cases though over 20 pg/ml were found in a few OLP, RAS and ABI. ABI exhibited the highest IL-6, and the cytokine level was lower in RAS, PMC, HGS and OLP in this order. Suppressed IL-6 activity was elevated with improvement of HGS lesion. TNF-alpha increased in 9 OLP, but the levels were below 100 pg/ml in all cases. Most SCC possessed higher GM-CSF activity than the controls. Increase of the cytokine corresponding with improvement of the oral lesion was seen in HGS, but not in OLP. From these results, each serum cytokine seems to reflect a characteristic pathophysiology of individual oral disorder. PMID- 1890663 TI - Mixed salivary glucose levels and candidal carriage in patients with diabetes mellitus. AB - The glucose concentration in unstimulated mixed saliva and serum was assayed and correlated with oral candidal colonization in 41 diabetics and 34 healthy control subjects. In diabetic patients, salivary glucose concentration was significantly higher than in the controls and was directly related to blood glucose concentration. Although the difference in the frequency and quantity of oral candidal isolation failed to reach significance between the two groups, diabetic patients who carried Candida intraorally had significantly higher salivary glucose concentrations than those in whom Candida could not be isolated. PMID- 1890665 TI - Experimental odontogenic tumors produced by ethylnitrosourea injections and mechanical injuries. AB - The present study was carried out to investigate odontogenic tumor induction in the rats by injections of carcinogen N-ethyl-N-nitrosourea (ENU) coupled with incisional wounds. The animals which received local injections of ENU in the region of incisor tooth germ of the right mandible every other day for 19 days after birth coupled with incisional wounding in the same region at 2 and 8 days, developed odontogenic carcinomas. However, the animals which were given local injections of ENU in the region of incisor tooth germ but did not receive incisional wounds, showed no pathologic changes. The animals which received both local injections of physiologic salt solution and incisional wounds in the same manner as mentioned above, did not exhibit any pathologic changes. The present results indicate that local administration of carcinogen ENU coupled with mechanical injuries, namely incisional wounding, caused the production of odontogenic carcinomas in the incisor region of the mandible in rats. PMID- 1890664 TI - The oral mucosa of the MRL/I mouse: a synoptic picture of systemic autoimmune disorders. AB - The oral manifestations of systemic autoimmunity were investigated in a kinetic study of the MRL/1 mouse. Lesions in the epithelium, connective tissue and minor salivary glands were characterized in serial sections of the soft palate and the cheeks with respect to 1) the type of inflammatory cells present, 2) the presence and type of vasculitis, 3) the presence of necrosis, 4) the occurrence of deposits. By the age of 16 wk, 100% of our animals had developed mild to severe lesions in at least one compartment of the mucosa. Between 16 and 32 wk of age, pathologic manifestations affected the epithelial and subepithelial tissues, the striated muscle tissue, the vascular system and, much less frequently, the minor salivary gland network. PMID- 1890666 TI - Residual cementoblastoma of the mandible. AB - An unusual case of a residual cementoblastoma in a 24-yr-old man is described. The final diagnosis has been based on the history and the clinical, radiographic and histologic features. The lesion has been removed in toto. During the ten-year follow-up no signs of recurrence have been noticed. PMID- 1890668 TI - Meet the challenge: health care in the 1990s. PMID- 1890667 TI - Dr. Katherine Chavigny speaks on the future of the LP/VN. PMID- 1890669 TI - Differentiated practice: another threat to the LPN? An opinion essay. PMID- 1890670 TI - LPN to RN student. Evolution of an affective change. PMID- 1890671 TI - Acoustic neuroma: a hidden killer. PMID- 1890672 TI - Counseling older adults with hearing impairment. PMID- 1890673 TI - The extended lateral arm flap: a new modification. AB - The lateral arm flap has been one of the mainstays in the armamentarium of microvascular reconstructive surgeons, especially in the cover of small to medium sized defects. Despite its many advantages, its widespread application has been limited by its small skin paddle. As a result of detailed anatomic and dye injection studies, it is possible to determine the actual extent of the cutaneous vascular supply of this flap, which is derived from the posterior radial collateral artery. This artery is found to extend significantly beyond the elbow and into the radial aspect of the upper forearm and, through clinical illustrations, it can be shown that a much larger flap can be harvested and used in a manner that is more versatile than the conventional lateral arm flap. PMID- 1890674 TI - Digital amputation, replantation, and cold intolerance. AB - In a controlled, retrospective, clinical study, the relationships between traumatic digital amputation, digital replantation, and cold intolerance were investigated. The results of the investigation indicate that cold intolerance is a major reason for disability after digital amputation. They also indicate that the cold intolerance experienced after digital replantation is due to the original injury, and that it is not aggravated by the reconstructive surgery. Cold intolerance, in and of itself, is not a contraindication to digital replantation, regardless of whether the patient lives or works in high- or low temperature environments. PMID- 1890675 TI - Cold ischemic damage to bone. AB - To clarify changes in bone tissue and osteogenetic ability after preservation under conditions of cold ischemic, a series of experiments were carried out using a rat model. Animals were grouped as follows: a group of 11 rats whose amputated legs were preserved in Euro-Collins solution at 4 degrees C for 24 hr and then transferred to the corresponding site of a different genetically similar rat; a group of seven animals whose amputated legs were preserved for 48 hr under the same conditions and transferred in the same way; and a control group of 11 animals whose legs were amputated and the femoral artery and vein left intact. After triple fluorochrome bone labeling of specimens obtained from all rats of these groups, decalcified and undecalcified sections were prepared and examined. In the cortical bone, ischemia led to spongy and irregular proliferation, increased lacunae, and decreased bone marrow cells and the bone marrow circulation was assumed to be more markedly impaired than the periosteal circulation. On fluorochrome bone labeling, specimens of the transfers preserved for 24 hr resembled those on the unoperated side, despite notable partial periosteal bone proliferation. In contrast, bone proliferation was obscure and irregular in specimens preserved for 48 hr. Bone morphology was well maintained, together with osteogenetic ability, after 24-hr preservation in Euro-Collins solution at 4 degrees C, although this was not possible after 48-hr preservation. PMID- 1890676 TI - Free groin flaps in microsurgical reconstruction of the extremity. AB - The authors performed free groin flap transplantation in 36 patients with extensive soft-tissue injury of the extremities. In each case, the vascular anatomy of the groin flap was analyzed during the operation. The anatomic classification of the superficial circumflex iliac artery according to its origin was as follows: a common origin with the superficial inferior epigastric artery in 15 cases (39.5 percent); an isolated origin and absent superficial inferior epigastric artery in 14 cases (36.8 percent), a separate origin in three cases (7.9 percent), and an origin from the profunda femoral artery in six cases (15.8 percent). These results are similar to those reported previously. The overall success rate was 72.2 percent. The success rate was better in the upper extremity (100.0 percent) than in the lower extremity (65.5 percent). Free vascularized groin flap transplantation is a suitable procedure for the one-stage reconstruction of severe soft-tissue injury, especially in the upper extremity. PMID- 1890677 TI - Laser-assisted venous anastomosis: a comparison study. AB - A low-powered carbon dioxide laser was used to perform 25 vein grafts (50 anastomoses) on the femoral veins of Sprague-Dawley rats. The patency rate, clamp time, and bleeding time were compared with 50 conventional microvascular vein grafts (100 anastomoses). The patency of the laser-assisted anastomoses (LAVA) was 84 percent, while the conventional vein grafts yielded a 94 percent patency rate. The average clamp time and bleeding time for the LAVA were 47.2 min and 4.88 sec, respectively, while the conventional anastomoses required 57.6 min and had an average bleeding time of 9.44 sec. Histologically, both specimens healed at the same rate, but the laser-assisted anastomoses produced less inflammation and granulation tissue. These results suggest that the laser has potential as a tool for clinical application in microsurgery. In addition, the 94 percent patency rate achieved with the vein interposition graft would suggest that a decrease in the tension across the anastomosis can improve patency. PMID- 1890678 TI - Topical use of Xylocaine for relieving vasospasm: effect of concentration. AB - The spasmolytic and antispasmodic effects of Xylocaine in different concentrations were studied. Twenty-five Wistar rats were divided into five groups according to the concentrations of Xylocaine used (2 percent, 4 percent, 10 percent, 20 percent, and 40 percent). The diameters of rat femoral arteries were measured with vernier calipers under the microscope. Effects were evaluated by the percentage of the test arterial diameter compared with that of the control contralateral artery. Vasospasm of both femoral arteries was produced by administration of the fresh blood of other rats. After immersion in the blood for 10 min. Xylocaine was administered into the right femoral artery for 10 min to examine its spasmolytic effect. The effects of the concentrations shown by the percent diameter were 106 percent, 108 percent, 107 percent, 111 percent, and 106 percent, respectively. There was no significant statistical difference between each agent and its control. Thirty minutes after removal of the agent, 2 percent Xylocaine failed to maintain its spasmolytic effect, while 4 percent, 10 percent, 20 percent, and 40 percent Xylocaine did maintain it. Next, blood was again administered after vessel immersion in the agent to examine its antispasmodic effect. The effects of the concentrations were 100 percent, 114 percent, 124 percent, 152 percent, and 146 percent. There were statistically significant differences, except in the case of 2 percent Xylocaine. Twenty-percent Xylocaine demonstrated a superior antispasmodic effect. The duration of the spasmolytic effect and the antispasmodic effect were concentration-dependent, up to approximately 20 percent. PMID- 1890679 TI - An investigation of venous pressure and oxygen tension in human extremities: an experimental study of survival in pedicled venous flaps. AB - The pedicled venous flap is used at various sites, such as the finger, forearm, and leg. The authors previously reported that the reasons for the viability of such flaps, based on the digital dorsal vein and used for repairing digital skin defects in the earlier study, were high venous pressure or oxygen tension, as well as the possible effects of plasmatic imbibition and outflow through the draining vein. To investigate the importance of venous pressure and oxygen tension in the survival of these flaps at other sites in the body, measurements were made comparing these parameters in the digital vein, cephalic vein, and greater saphenous vein, which are all used clinically as draining veins in pedicled venous flaps. Although measurements in other sites were consistently lower than in the digital dorsal vein, since these other venous flaps are nevertheless viable in the clinical situation, their viability may not be due only to relatively high venous pressure and oxygen tension. The authors intend to carry out further comparative studies on plasmatic imbibition in the flap and outflow through the draining vein. PMID- 1890680 TI - CO2 laser-assisted microvascular anastomosis: biomechanical studies and clinical applications. AB - Experiments have been performed using CO2 laser-assisted microvascular anastomoses, and they demonstrated the following features, in comparison with conventional anastomoses: ease in technique; less time consumption; less tissue inflammation; early wound healing; equivalency of patency rate and inner pressure tolerance; but only about 50 percent of the tensile strength of manual-suture anastomosis. Six clinical applications in 16 vessels are reported, using this procedure. The preliminary results of these cases would appear to be the first successful replantations and free tissue transfers using CO2 laser-assisted microvascular anastomoses in man. The procedure offers increased safety and speed in microvascular anastomoses. PMID- 1890681 TI - Combined therapy with antithrombotic agents and radical scavengers for reperfusion injury of flaps. AB - The usefulness of combining antithrombotic agents and radical scavengers in the treatment of reperfusion injury (an almost ideal approach) was substantiated using an ischemic flap model. The cause(s) of reperfusion injury was hypothesized on the basis of differences in effects between antithrombotic agents and radical scavengers in the experimental groups. Flap specimens were also obtained regularly for histologic examination. The experiment was conducted in nine rabbit groups. For continuous treatment with intraarterial antithrombotic agents, both heparin and urokinase were continuously injected at respective administration rates of 20 U/kg/hr and 200 IU/kg/hr for seven consecutive days immediately before reperfusion. For intraarterial radical scavenger treatment, a solution of both 30,000 U/kg SOD and 30,000 U/kg catalase in 5 ml of a lactated Ringer's solution was injected over a period of about 30 min immediately before reperfusion. The ischemic time of the flaps was 10 hr for Group I and 12 hr for Group II. Each group was comprised of subgroups a, b, c, and d: a = control; b = continuous intraarterial antithrombotic agent injection; c = intraarterial lactated Ringer's solution alone; and d = intraarterial radical scavenger injection. For Group II, an additional subgroup e was established, which received continuous injection of both intraarterial antithrombotic agents and injected intraarterial radical scavenger. In the 10-hr ischemic treatment group, an effect was obtained by continuous intraarterial antithrombotic agents alone. In the 12 hr ischemic treatment group, a significant improvement in flap-take ratio was obtained using intraarterial radical scavenger, in combination with antithrombotic agents. Observation of the flaps that survived in subgroups Ib and IIe revealed skin thinning, vascular wall thickening, and muscular tissue degeneration, although the skin architecture was well preserved. PMID- 1890682 TI - Intraneural vascular investigative techniques. AB - Research into peripheral nerve grafting and repair is progressing at a rapid rate. An exciting aspect of these investigations concerns the intraneural vascular system and its nutrient supply. This review is an approach to selecting an appropriate laboratory investigative technique to aid in experimental design. PMID- 1890683 TI - Electron probe X-ray microanalysis of intracellular element concentrations in cryosections in the presence of changes in cell volume. AB - The interpretation of element concentration data for X-ray microanalyses of biological tissues, which are subjected to some experimental treatment, can be complicated by changes in cell volume and total cell dry matter induced by the treatment. We have examined the manner in which such changes would affect the values measured in frozen-dried cryosections of soft tissues, and how they may be taken into account in the interpretation of the results. The element content (mass per unit dry weight) measured by the peak-to-continuum or Hall method is independent of changes in cell volume, but is sensitive to a change in the local dry mass. Conversely, intracellular concentrations in terms of mass per unit volume, as determined by the peripheral or internal standard technique, are dependent on volume changes but independent of dry mass. The estimated dry weight fraction is affected by changes in both volume and dry mass. The results obtained from both quantification methods can therefore provide information on the combination of changes in cellular element levels, volume and total dry mass that may occur following the experimental treatment. In a study of the late effect of the drug cisplatin on electrolyte concentrations in kidney proximal tubules, both quantification methods have been used to obtain wet weight and dry weight concentrations. By applying the above considerations, the analytical results have been interpreted as a combination of changes in element levels and a shrinkage of the tubule cells. Cell shrinkage was confirmed by morphometric analysis of tubular cross-sections. PMID- 1890684 TI - A device for freeze-substituting a large number of samples under controlled conditions. AB - An inexpensive device for reproducible freeze-substitution is described. The equipment consists of a reciprocating shaker, holding vials of substitution fluid, mounted in the gas phase of a large liquid nitrogen refrigerator. The shaker temperature is controlled by a programmable microprocessor. PMID- 1890685 TI - Immunoelectron microscopic localization of elastic tissue components in archival tissue samples. AB - Tissue samples that have been stored for many years, in different media and under a variety of conditions, have been examined by modern techniques of immunoelectron microscopy, using antibodies against elastic tissue components. A range of postembedding restorative procedures has been identified, which will allow reliable immunolocalization of antibodies against the elastic tissue component of such specimens. These methods have been applied successfully to autopsy-derived material, fixed in buffered formaldehyde, to archival material stored frozen at -70 or -20 degrees C, to specimens fixed for electron microscopy and stored for many years in buffer, and even to archival material from formaldehyde-fixed, paraffin-embedded blocks, reprocessed for electron microscopic examination. The successful restorative methods included pre treatment of the sections with 6 M guanidine hydrochloride, or 1 M Tris/saline, each containing 100 mM dithiothreitol (a reducing agent) followed by alkylation with 220 mM iodoacetamide. The application of these techniques allowed reliable study of elastic tissue antibody distributions in archival tissues that could not be obtained again, as well as comparative studies with tissues processed many years previously. PMID- 1890686 TI - Collagen type conservation during metamorphic repatterning of the dermal fibers in salamanders. AB - The orientation of the fibers in the dermis of the tiger salamander, Ambystoma tigrinum, undergoes a dramatic repatterning at metamorphosis. The pre metamorphic, larval dermis is a tight layer composed of crossed fibers that wind helically around the trunk. This condition is retained by neotenic adults which do not undergo metamorphosis. In contrast, the neotenic adults which do not undergo metamorphosis. In contrast, the metamorphosed adult dermis consists of a superficial, loose network of fibers invested with large multicellular glands- the stratum spongiosum--and a deeper tight layer of fibers--the stratum densum. However, unlike the crossed fibers of the pre-metamorphic dermis, there is no preferred orientation to the fibers in either layer of the post-metamorphic dermis. In order to evaluate whether these two distinctly different fiber patterns are constructed from biochemically similar fibers, the collagen types present in the pre- and post-metamorphic dermis were determined using SDS polyacrylamide gel electrophoresis. Type I collagen is the predominant collagen of the dermis and the same major collagen types are present for all individuals, whether pre- or post-metamorphic. Thus, the major types of collagen that compose the dermal fibers do not change during metamorphic repatterning of the dermis. PMID- 1890687 TI - Light and scanning electron microscopic studies on effects of marine algal toxins toward freshly prepared hepatocytes. AB - Mussels exposed to dinoflagellates may represent a human health risk due to accumulation of a variety of algal toxins. In several parts of the world, algal toxins leading to diarrhea (diarrhetic shellfish poisons, DSP) are found in mussels for extended periods of the year. Routine monitoring of these toxins involves ip injections in mice. Chemical analytical methods have been developed for only some of the toxins in question, namely, those giving diarrhea. Other toxins in the DSP complex are not easily detected by analytical methods. In this report we show that freshly prepared hepatocytes from rats are a convenient means to differentiate between the toxins that give diarrhea and those that do not. Consequently, hepatocytes can be useful in both screening and as a tool in the process of developing analytical methods. Freshly prepared hepatocytes might be useful in combination either with the mouse bioassay or with chemical analytical methods. PMID- 1890688 TI - Effects of beryllium metal particles on the viability and function of cultured rat alveolar macrophages. AB - The physicochemical properties of particles influence their in vivo toxicity following deposition in the respiratory tract. To evaluate the relative contributions of mass and surface area to particle-induced toxicity, rat pulmonary alveolar macrophages (PAM) were exposed to four types of particles in vitro. We used three beryllium metal samples: relatively large (Be-II) and relatively small (Be-V) sized fractions of beryllium metal obtained from an aerosol cyclone, and a beryllium metal aerosol generated by laser vaporization of bulk beryllium metal in an argon atmosphere (Be-L). We also used glass beads (GB) as a negative control particle. End points examined included cell viability, determined by trypan blue dye exclusion, and changes in phagocytic ability, measured by counting the number of sheep red blood cells internalized by the PAM. Phagocytic ability was inhibited by exposure to beryllium particles at concentrations that did not cause appreciable cell death. Results describing effects based on the mass concentration of particles in culture medium were transformed by the amount of specific surface area of the particles to permit the expression of toxicity relative to the amount of particle surface per unit volume of culture medium. On a mass basis, the order of particle-related cytotoxicity was Be-L greater than Be-V greater than Be-II greater than GB, and for inhibition of phagocytosis, the order was Be-L approximately Be-V greater than Be-II greater than GB. When analyzed on a specific surface area basis, the cytotoxicity of the different materials became more similar in a fashion that was largely predicted by the amount of surface of the particles administered. However, because differences in specific surface area among the beryllium particle samples did not entirely predict cytotoxicity, we concluded that factors in addition to specific surface area influenced the expression of toxic effects in cultures of PAM exposed to beryllium metal. PMID- 1890689 TI - Lymphocyte proliferation assays as potential biomarkers for toxicant exposures. AB - Recently there has been interest in developing assays that can be used as indicators (biomarkers) of exposure to toxic agents. We have been exploring the potential utility of three lymphocyte proliferation assays [the responses of B lymphocytes to the mitogen lipopolysaccharide (LPS), the responses of T lymphocytes to the mitogen concanavalin A (ConA), and the responses of T lymphocytes to antigenic stimuli in a mixed lymphocyte culture (MLC) assay] as biomarkers of toxicant exposure. Studies were initiated to assess the applicability and specificity of these assays and to investigate the mechanisms by which toxicants alter lymphocyte proliferation. All studies were performed using cells isolated from Fischer 344 rats. To assess applicability, mitogen assays were performed using in vitro exposures to eight different toxicants: hydroquinone, benzoquinone, Aroclor 1254, styrene oxide, and the salts of mercury, cadmium, chromate, and nickel. In vitro concentrations spanned five orders of magnitude (100 to 0.01 mg/l). At the lowest concentration tested, all eight compounds induced changes in at least one mitogen assay, indicating that these assays may be applicable to a wide range of toxicants. Variations of the ConA and MLC assays were used to test for specificity. In both assays, splenocytes taken from rats exposed in vivo to either chromate or to cadmium responded differently when the cells were cocultured with exogenously added chromate or cadmium ions, indicating that it may be possible to detect exposure to a specific toxicant by performing modified lymphocyte proliferation assays. In the mechanistic studies, splenocytes from cadmium and chromate-treated rats altered the ConA-induced proliferation of cocultured syngeneic cells. In addition, the antigenicity of splenocytes isolated from cadmium-treated rats was enhanced when these cells were used as stimulators for allogeneic splenocytes. The results of these studies indicate that lymphocyte proliferation assays may be useful for detecting exposure to a wide range of toxicants and that variations of these assays may be useful for implementing immunologically based tests for detecting exposures to specific chemicals. PMID- 1890690 TI - Phosphylation kinetic constants and oxime-induced reactivation in acetylcholinesterase from fetal bovine serum, bovine caudate nucleus, and electric eel. AB - Kinetic constants for selected phosphonate and phosphinate inhibitors of fetal bovine serum acetylcholinesterase (FBS AChE; EC 3.1.1.7), bovine caudate nucleus AChE (BCN AChE), and eel AChE have been determined. Oxime reactivation of the phosphylated enzymes has also been evaluated. In general, a rank order with respect to organophosphorus compound (OP) inhibition of the enzymes was observed: soman (pinacolyl methylphosphonofluoridate) was found to be the most potent inhibitor, and 4-nitrophenyl methyl(phenyl)phosphinate (PMP) the least potent. On average the bimolecular rate constant for soman inhibition of eel AChE was nearly twofold greater (9.3 x 10(7) M-1 s-1) than that for FBS AChE (5.5 x 10(7) M-1 s 1) and nearly fourfold greater than that for BCN AChE (2.2 x 10(7) M-1 s-1). In addition, 4-nitrophenyl chloromethyl(phenyl)phosphinate (CPMP) inhibition of eel AChE on average was nearly 10-fold greater than FBS AChE and three orders of magnitude greater than BCN AChE. The oxime HI-6 reactivated soman phosphonylated enzymes to a considerably greater extent than other oximes, and FBS AChE was notably more responsive to HI-6 than to other oximes. The individual mean values of the ki for each inhibitor in each class (phosphonate or phosphinate) were different with respect to each AChE, which may be a reflection of differences in enzyme configuration, whereas the general rank order of inhibitor potency within each class, reflected by the ki, was similar with respect to each AChE, which may be related to similar active centers. In general, oxime potency and some rank order varied with each inhibitor and with each AChE, although there was some similarity in oxime rank order between the two mammalian AChEs. Overall, the data support the selection of FBS AChE as the enzyme of choice for in vitro testing of OP inhibitors and reactivators. PMID- 1890691 TI - Evaluation of 2-methoxyacetic acid toxicity on mouse germ cells by flow cytometry. AB - Flow cytometric (FCM) DNA content measurements were carried out on testicular monocellular suspensions obtained from mice exposed per os to a single dose of 50, 100, 300, 600, and 900 mg/kg body weight (b.w.) of 2-methoxyacetic acid (MAA) in order to investigate its cytotoxic action on germ cells. The effects of MAA were evaluated 2, 7, 14, 28, and 45 d after treatment in terms of altered cell type ratios in FCM fluorescence distribution histograms. Testis weight and histological tissue sections were also analyzed. MAA induced marked changes in the relative percentages of tetraploid and haploid cells, indicating the occurrence of cytotoxic damage on primary spermatocytes. Multiparameter FCM analysis showed that, besides its action on nucleic acid synthesis, MAA can also affect the cellular energy metabolism reflected in an altered mitochondrial mass distribution on round spermatids surviving the MAA treatment. This study demonstrates that rapid and unique FCM procedures can be usefully applied in reproductive toxicology. PMID- 1890692 TI - The ability of short-term tests to predict carcinogenicity can be summarized in a single index. AB - This paper presents a new procedure aimed at quantifying the ability of short term tests (STT) to discriminate between carcinogens and noncarcinogens. While the sensitivity, specificity, and accuracy indices provide an estimate that is not biased by the relative proportion of carcinogens and noncarcinogens of the different databases, the new index, called Relative Operating Characteristics (ROC), goes a step further, and overcomes the problem of the decision criterion bias. In fact, if the threshold--that is, minimum increase over the control above which an STT result is positive--is varied, sensitivity and other factors are also consequently affected. A similar problem occurs when the STTs are assembled in batteries: the performance of the battery in discriminating between carcinogens and noncarcinogens depends on the preliminary decision of how many and which assays should be positive for considering a chemical as positive in the battery. The ROC analysis produces a single value, which places the performance of different systems on a common, easily interpreted scale (instead of using several different indices such as sensitivity, etc.). Most importantly, this index is independent of the decision criterion bias; consequently it is the best measure of the true ability of STTs to discriminate between carcinogens and noncarcinogens. To illustrate the approach, the ROC analysis is applied to a battery composed of the four in vitro assays studied by the U.S. National Toxicology Program: the analysis confirmed the previous results, pointing to the limited ability of this battery to discriminate between carcinogens and noncarcinogens. PMID- 1890694 TI - Effects of crude oil and ultraviolet radiation on immunity within mouse skin. AB - Previous studies indicate that crude oil leads to increased pigmentation and erythema (sunburn) in response to sunlight in exposed individuals. However, no information is currently available concerning whether crude oil exposure might enhance the immunosuppressive effects of solar ultraviolet radiation (UVR) on the skin. In order to address this question, the back skin of shaved, female C3H/HeN mice was exposed to crude oil with or without subsequent treatment with medium wavelength (UVB) (200 J/m2) or long-wavelength (UVA) (20,000 J/m2) UVR. Immune function was assessed in treated mice by measuring their ability to mount contact hypersensitivity responses to a hapten (2,4-dinitro-1-flyorobenzene, DNGFB) applied to the site of crude oil and UVR treatment as determined by ear swelling upon subsequent challenge. Since Langerhans cells represent an important component of immunity within the skin and because suppression of contact hypersensitivity following UVR treatment is often accompanied by disappearance of Langerhans cells from the epidermis, the impact of these agents on epidermal Langerhans cell density was also analyzed. This was accomplished by enumerating IA-positive cells within the epidermis of treated skin. In these studies, crude oil alone induced inhibition of contact hypersensitivity but had no effect on epidermal Langerhans cells. In contrast, combined treatment with crude oil and UVA led to suppression of contact hypersensitivity, which was accompanied by depletion of epidermal Langerhans cells. PMID- 1890693 TI - Comparative toxicity and tissue distribution of antimony potassium tartrate in rats and mice dosed by drinking water or intraperitoneal injection. AB - Antimony potassium tartrate (APT) is a complex salt that until recently was used worldwide as an antischistosomal drug. Treatment was efficacious only if APT was administered intravenously to humans at a near lethal total dose of 36 mg/kg. Because unconfirmed epidemiologic studies suggested there might be an association between APT treatment and bladder cancer, we initiated prechronic toxicity studies with the drug to select a route of administration and doses in the event that chronic studies of APT were needed. The toxicity and concentration of tissue antimony levels were compared in 14-d studies with F344 rats and B6C3F1 mice administered APT in the drinking water or by ip injection to determine the most appropriate route for longer term studies. Drinking water doses estimated by water consumption were 0, 16, 28, 59, 94 and 168 mg/kg in rats and 0, 59, 98, 174, 273, and 407 mg/kg in mice. APT was poorly absorbed and relatively nontoxic orally, whereas ip administration of the drug caused mortality, body weight decrements, and lesions in the liver and kidney at doses about one order of magnitude below those in drinking water. Because of these data and the dose related accumulation of antimony in the target organs, an ip dose regimen was selected for subsequent studies. Both sexes of F344 rats and B6C3F1 mice were given 0, 1.5, 3, 6, 12, and 24 mg/kg doses of APT every other day for 90 d by ip injection. There were no clinical signs of toxicity nor gross or microscopic lesions in mice that could be attributed to toxicity of APT, although elevated concentrations of antimony were detected in the liver and spleen of mice. Rats were more sensitive than mice to the toxic effects of APT, exhibiting dose related mortality, body weight decrements, and hepatotoxicity. The concentrations of antimony measured in liver, blood, kidney, spleen, and heart of rats were proportional to dose, but there were no biochemical changes indicative of toxicity except in the liver. Hepatocellular degeneration and necrosis occurred in association with dose-related elevations in activities of the liver-specific serum enzymes sorbitol dehydrogenase and alanine aminotransferase. By alternating the site of abdominal injection and the days of treatment, mesenteric inflammation at the site of administration was minimized in the rats and mice, indicating that the ip route would be suitable for chronic studies.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1890695 TI - Inhibition of intercellular communication in Chinese hamster V79 cells by fractionated asphalt fume condensates. AB - Asphalt fume condensate is a skin carcinogen in mice, yet this complex mixture contains relatively low levels of known carcinogenic initiators. Consequently, its biological activity has been attributed to the presence of cocarcinogenic or tumor-promoting agents. One of several proposed mechanisms of tumor promotion is inhibition of intercellular communication. In an attempt to determine if asphalt fume has tumor-promoting potential inhibition of intercellular communication was measured in V79 cells exposed to fractionated asphalt fume condensate. Fume from air-blown Arabian crude asphalt was trapped and separated into five fractions by preparative-scale high-pressure liquid chromatography. The parent fume condensate and the five fractions inhibited intercellular communication in a concentration dependent fashion, with a minimum effective concentration of 2.5 microgram/ml for the most potent fraction. Cytotoxicity assays were performed at the same time and concentrations as the metabolic cooperation assays. Cytotoxic responses paralleled the inhibition of intercellular communication. PMID- 1890696 TI - Differential regulation of S100 beta and mRNAs coding for S100-like proteins (42A and 42C) during development and after lesion of rat sciatic nerve. AB - The changes in the levels of S100 beta (a protein that stimulates neurite extension and neuronal survival) and 42A and 42C (S100-like proteins whose mRNAs are induced in PC12 cells by nerve growth factor) during development and after rat sciatic nerve lesions were analyzed. S100 beta, 42A, and 42C mRNAs showed differential regulation during development. S100 beta mRNA was present both in sciatic nerve and brain, and increased more than 11-fold during the first 3 wk of nerve postnatal development. 42A and 42C mRNAs were essentially restricted to sciatic nerve, with little found in either embryonic or adult brain. The levels of 42C and 42A mRNAs in sciatic nerve increased 4- and 14-fold, respectively, by postnatal day 23 compared to postnatal day 2. 42A, 42C, and S100 beta mRNAs also showed a differential regulation during sciatic nerve degeneration and regeneration. Axotomized and control sciatic nerves were examined by Northern blots at various times after a crush or cut injury. 42A and 42C mRNA levels increased rapidly in the distal segment of axotomized nerve, remained two- to five-fold higher than controls at day 14 after injury but returned to control levels by 40 days. In contrast, S100 beta mRNA showed a three-fold decrease in the axotomized nerve between days 1 and 3 after injury, and slowly returned towards control levels over the next few weeks. The decrease in S100 beta mRNA was reflected by a corresponding decrease in S100 beta protein levels. The induction of 42A and 42C mRNAs and repression of S100 beta mRNA remained if nerve regeneration was prevented.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1890697 TI - Developmental and regional expression of choline acetyltransferase mRNA in the rat central nervous system. AB - The developmental and regional expression of choline acetyltransferase (ChAT) mRNA was examined in the rat brain and spinal cord by northern blot analysis and in situ hybridization. ChAT mRNA expression in the brain showed a biphasic increase during development, with a first peak at two weeks postnatally, a marked decrease by the third week, and a second increase between the third and fifth week after birth, indicating that emergence of the cholinergic phenotype occurs at different times in different brain regions. In the spinal cord, ChAT mRNA was detected at similar levels from embryonic stage 13 (E13) until birth, increasing thereafter until adulthood. In the adult rat central nervous system, high levels of ChAT mRNA were detected in the spinal cord and brain stem structures. Lower levels were seen in midbrain, septum, striatum, thalamus, and olfactory bulb. ChAT mRNA containing cells were identified by in situ hybridization in the olfactory tubercule, piriform cortex, striatum, several basal forebrain nuclei, and spinal cord. A nearly two-fold increase in adult spinal cord ChAT mRNA levels were seen one week after a bilateral crush lesion of the sciatic nerve, indicating that ChAT mRNA expression is regulated during motoneuron regeneration. PMID- 1890698 TI - Olfactory Schwann cells are derived from precursor cells in the olfactory epithelium. AB - In this morphological and immunohistochemical study we show that olfactory schwann cells (OSC) are derived from precursor cells residing in the olfactory epithelium. During development, they migrate out of the epithelium and extend processes to ensheath the olfactory axons. Olfactory mucosa from E14 rat embryos and juvenile rats were treated with trypsin-pancreatin to remove the underlying connective tissue. The epithelial explant was then maintained for two days in culture, during which cells migrated out from the explant. Among them were spindly bipolar cells which were identified as OSC by their positive immunoreaction for glial fibrillary acidic protein, ultrastructure, and association with growing axons. Axonal growth was significantly more profuse in the embryonic explants, in which the polarity of the OSC was oriented parallel with the axons. Ultrastructural observations showed that ensheathment of the bundles of axons resembled those in vivo. PMID- 1890699 TI - Effects of sphingosine on phorbol ester-mediated changes in astrocyte morphology and protein phosphorylation. AB - Previous studies indicate that phorbol myristate acetate (PMA) can induce morphological changes in astrocytes cultured from the rat neocortex. PMA also increased 32P incorporation into several proteins, including glial fibrillary acidic protein (GFAP), vimentin, and proteins with molecular weights of 80,000 (pI 4.5), 50,000 (pI 4.9), and 30,000 (pI 5.5). The present studies were conducted to determine if the morphological effect and the phosphorylation effect of PMA could be blocked by treatment with sphingosine, a protein kinase C inhibitor. Treatment with 15 microM sphingosine inhibited the effect of PMA on astrocyte morphology. This agent also inhibited the increase in phosphorylation mediated by PMA. The percent inhibition ranged from approximately 20% for the 30,000-Mr protein to 70% for GFAP. Analysis of phosphorylation sites on GFAP and vimentin using two-dimensional tryptic mapping techniques indicate that the partial inhibition of phosphorylation is likely the consequence of partial inhibition of protein kinase C rather than a selective inhibition at some phosphorylation sites and not others. In addition to increasing 32P incorporation into various proteins, PMA also decreased 32P incorporation in several 20,000-Mr proteins (pI values of 6.7, 6.4, 6.2, 4.9). However, this effect was not blocked by treatment with sphingosine. This suggests that the actions of PMA to increase and decrease 32P incorporation are mediated by different mechanisms. PMID- 1890700 TI - Acetylcholinesterase distribution in subpopulations of murine thymocyte. AB - The presence of acetylcholinesterase has been detected in the thymus of several species both biochemically and histochemically. In this study we have investigated the molecular forms and the level of this enzyme in separate compartments of the murine thymus and in different thymocyte subpopulations. Similar levels of acetylcholinesterase activity are present both in thymocytes and in the stromal component. Sucrose density gradient analysis revealed the presence of a single molecular form of about 5 S, presumably a dimeric form. Moreover the results demonstrate a preferential association of AChE with mature thymocyte subsets (Peanut Agglutinin negative and Corticoresistant). This finding correlates with the preferential sensitivity of these cells to cholinergic drugs and supports the hypothesis that acetylcholinesterase modulates the cholinergic effects on thymocytes. PMID- 1890701 TI - Chondroitin sulfate proteoglycan surrounds a subset of human and rat CNS neurons. AB - Chondroitin sulfate proteoglycan (CS-PG) bearing glycosaminoglycan (GAG) chains containing unsulfate (COS) and 6-sulfate (C6S) disaccharides was immunolocalized in rat and human CNS by using monoclonal antibodies (MAb) specific for the two disaccharides. The immunostaining with both MAb was restricted to the periphery of a neuronal subset in rat and human CNS. Double immunofluorescence showed codistribution of the antigens around the same neuronal population. The staining with anti-COS MAb was stronger than with anti-C6S MAb, suggesting that the proteoglycan (PG) contains mainly COS disaccharides. In different rat cortical areas, 40-60/mm2 positive interneurons were found, the visual cortex showing the highest value. In human cortex, positivity was also observed around the soma of some pyramidal cells. In the rat, positive neurons were also localized in deep cerebellar nuclei, reticular nucleus of the thalamus, and other structures of the midbrain and hindbrain. CA3 region of hippocampus and the external layer of pyriform cortex were characterized by positivity of the neuropil. Immunoelectronmicroscopy showed the antigens in the extracellular space around the neuronal soma, the synaptic elements and the cell processes of the neuropil. The neuronal surface of the soma and of the proximal dendrites were positive, but the pre- and postsynaptic membranes and clefts were negative. PMID- 1890702 TI - Oligodendrocytes of the jimpy phenotype can be partially restored by environmental factors in vivo. AB - Cross-transplantations of neural tissue between jimpy (jp) shiverer (shi) and normal mice have been performed under heterochronic conditions. In all series, fragments of E14-E15 embryonic neural tissue from the different donors have been transplanted into newborn host brain in order to study environmental influences by differentiated tissue on transplanted embryonic cell lines. Large patches of proteolipid protein (PLP)-positive myelin have been observed in the jp brain after transplantation of shi or normal embryonic tissue into the newborn jp brain, suggesting that the jp parenchyma did not inhibit the differentiation of other oligodendrocytes (ODCs). Jp embryonic tissue had the same mitotic potential as normal tissue, as demonstrated by the larger size of myelin patches observed when jp embryonic tissue was used instead of newborn jp tissue. By contrast, whatever the conditions, jp myelin patches were always obviously smaller than normal or shi myelin patches, suggesting that the myelinating capacity of jp ODCs was not enhanced by environmental factors. Finally, comparison of the ratio of successful outcomes observed following embryonic vs. newborn jp donor tissue, strongly suggests a partial or total normalization of jp embryonic ODCs survival by a more mature shi environment. PMID- 1890703 TI - Developmental modulation of physicochemical variants of the tailed asymmetric (16S) acetylcholinesterase by neuromuscular activity and innervation in the mouse embryo. AB - We have studied the physicochemical properties of acetylcholinesterase (AChE) during embryonic development of normal and functionally impaired mouse skeletal muscle, focusing on the tailed asymmetric (16S) form of the enzyme. The muscle specific 16S AChE exists in two different variants. One is associated with extracellular matrix and is high-salt soluble (HSS, also termed hydrophilic AChE), whereas the other form is anchored to cell membranes and is detergent extractable (DE, or hydrophobic AChE). Before innervation during normal embryonic development, both hydrophilic and hydrophobic 16S AChE exist in equal amounts. After muscle innervation, there was an increase (amounting three-fold on E18) in the levels of hydrophilic vs. hydrophobic 16S AChE. This alteration of the relative proportions of the two variants of 16S AChE did not occur in chronically inactive muscles either from the mouse mutant, muscular dysgenesis, or from tetrodotoxin-treated mouse embryos. Taken together with previous reports, the present results suggest that postsynaptic membrane depolarization-induced Ca2+ fluxes are important in modulating not only the synthesis of 16S AChE, but also the relative proportions of both physicochemical variants of this molecular form of AChE. PMID- 1890704 TI - Synthesis, purification, and characterization of human ciliary neuronotrophic factor from E. coli. AB - The cDNA for human ciliary neuronotrophic factor (CNTF) has been cloned into an expression vector under the control of the T7 promoter. The BL21 strain of E. coli was transformed with this vector. Human CNTF accounted for about 30% of the total bacterial protein after induction with isopropyl-B-D-thiogalactopyranoside. This human CNTF was purified to homogeneity from inclusion bodies by a combination of ion exchange chromatography and reverse-phase high performance liquid chromatography. The amino-terminal amino acid sequence of the purified protein was identical to the deduced amino acid sequence; however, the methionyl residue has been removed. On SDS-PAGE gels, human CNTF displayed a molecular weight of about 24 kDa, in accord with its deduced molecular mass; a pI of 5.8 indicates the acidic nature of the molecule. A proposed structure for human CNTF includes major alpha helical regions. The ED50 of purified human CNTF was approximately 30 pM, using cultured embryonic day 10 chicken dorsal root ganglion neurons; no activity was observed with neurons from embryonic day 8 ganglia. Polyclonal antibodies prepared against both a synthetic peptide of CNTF and the entire human CNTF protein recognized a single 24 kDa band on Western blots, corresponding to human CNTF. However, only the antibodies against intact CNTF blocked its biological activity. This represents the first molecular expression and purification of human CNTF. PMID- 1890706 TI - From the Food and Drug Administration. PMID- 1890705 TI - Mitochondrial DNA: a new frontier in acquired and inborn gene defects. PMID- 1890707 TI - From the Centers for Disease Control. Tobacco use among high school students- United States, 1990. PMID- 1890708 TI - A piece of my mind. International medical graduates in the United States. An interview with Sir William Osler. PMID- 1890709 TI - Upper-body fat distribution and endometrial cancer risk. AB - STUDY OBJECTIVE: --To determine if body fat distribution affected endometrial cancer risk. DESIGN: --Case-control study. SETTING: --This study was carried out at the H. Lee Moffitt Cancer Center at the University of South Florida, Tampa, where all patients in the case group received their diagnoses and histological confirmations. PATIENTS: --Forty consecutive women newly diagnosed with endometrial cancer and 40 controls matched for age and Quetelet index. MAIN OUTCOME MEASURES: --Anthropometric measurements were taken for the abdomen, thigh, suprailiac, subscapular, biceps, and triceps skin fold thicknesses; waist and hip circumferences, weight, and height. Relative risks for endometrial cancer were calculated according to these anthropometric measurements. RESULTS: --Case patients with endometrial cancer had significantly greater waist-to-hip circumference ratios (P less than .001), abdomen-to-thigh skin fold ratios (P less than .01), and suprailiac-to-thigh skin fold ratios (P = .02) compared with control subjects matched for age and Quetelet index. The relative risk for endometrial cancer increased with an increasing waist-to-hip circumference ratio (less than or equal to 1.14 = 1.0; greater than 1.14 = 15.0), with an increasing abdomen-to-thigh skin fold ratio (less than or equal to 0.82 = 1.0; greater than 0.82 = 5.0), and with an increasing suprailiac to-thigh skin fold thickness ratio (less than or equal to 0.67 = 1.0; greater than 0.67 = 3.50). CONCLUSION: --Upper body fat localization is a significant risk factor for endometrial cancer in women matched for age and Quetelet index. PMID- 1890711 TI - Continuous quality improvement. Concepts and applications for physician care. AB - There has been a growing interest by health care leaders in the continuous quality improvement method of quality management. This method uses measurements of quality "indicators" to initiate and drive organizational changes in a never ending cycle of continuous improvement. Many discussions of the continuous quality improvement method have emphasized the organizational and attitudinal changes necessary to fully implement the model while deemphasizing the uses of measures of quality to guide improvement. In this article, we emphasize the concepts behind the measurement of quality that underline the continuous quality improvement model and give examples of how these concepts can be immediately applied to guide improvement in the quality of physician care. PMID- 1890710 TI - Hypoxemia is associated with mitochondrial DNA damage and gene induction. Implications for cardiac disease. AB - OBJECTIVE: --Oxidative phosphorylation (OXPHOS) deficiency due to hypoxemia or other causes was hypothesized to increase oxygen radical generation, damage mitochondrial DNA (mtDNA), and reduce adenosine triphosphate synthesis, resulting in compensatory OXPHOS gene induction. Therefore, we investigated the levels of mtDNA damage and OXPHOS transcripts in normal and ischemic hearts, and then in other forms of heart disease. DESIGN: --DNA was extracted from the heart and the levels of the common 4977 base pair mtDNA deletion were quantitated as an index for mtDNA damage. Total RNA was extracted from hearts and analyzed for OXPHOS transcript levels. RESULTS: --In control hearts, the 4977 base pair mtDNA deletion appeared at age 40 years and reached a maximum deletion of 0.0035%. Much higher levels were found in ischemic hearts (0.02% to 0.85%), as well as in three of 10 cases with other types of heart disease (0.017% to 0.16%). The OXPHOS transcripts were increased in all diseased hearts. CONCLUSION: --Ischemic hearts have increased mtDNA damage and OXPHOS gene expression, suggesting that mtDNA damage is associated with OXPHOS deficiency. Oxidative phosphorylation defects may also play a role in some other forms of cardiac disease. PMID- 1890712 TI - Bias against negative studies in newspaper reports of medical research. AB - OBJECTIVE: --To assess if the reporting of controversial medical journal articles by newspapers reflects the existence of a bias against negative studies (those showing no effect), we compared the rates of newspaper reporting of two studies, one negative and one positive, published back-to-back in the March 20, 1991, issue of JAMA. Both studies analyzed an area of public health concern, radiation as a risk for cancer. DESIGN: --Seven computerized on-line databases were screened for daily newspapers published in North America during the week following JAMA's publication of the two studies. These databases had full-text access to 168 daily newspapers. Newspapers identified with reports of the two studies were analyzed for length and quality of the reports. RESULTS: --Seventeen newspapers, publishing 19 reports on the two studies, were identified. Nine reports were dedicated solely to the positive study and 10 reports covered both studies. None of the reports were dedicated to the negative study only. In reports covering both studies, the mean length of the positive reports was significantly longer than the mean length of the negative reports (354 +/- 181 words vs 192 +/- 178 words; P = .04). The mean quality score of the positive reports was significantly higher than that of the negative reports (10.1 +/- 3.4 vs 5.9 +/- 4.9; P = .02). CONCLUSIONS: --The number, length, and quality of newspaper reports on the positive study were greater than news reports on the negative study, which suggests a bias against news reports of studies showing no effects or no adverse effects. PMID- 1890713 TI - Priorities in professional ethics and social policy for human genetics. PMID- 1890714 TI - The Lasker Awards--honoring the spirit of medical science. PMID- 1890716 TI - The 1991 Albert Lasker Public Service Award. From egg to organism. Studies on embryonic pattern formation. PMID- 1890715 TI - The 1991 Albert Lasker Public Service Award. Women's reproductive health. A chronic crisis. PMID- 1890717 TI - Exploring the options. PMID- 1890718 TI - Nontraditional medical pursuits. PMID- 1890719 TI - Consulting: MDs behind the scenes. PMID- 1890720 TI - Weighing the benefits of combined residency programs. PMID- 1890721 TI - [Clinical and pharmacokinetics studies of ceftriaxone upon 2g once daily administration in respiratory tract infections]. AB - Clinical studies on ceftriaxone (CTRX) were conducted with 2 g once daily administration to respiratory tract infections. In addition, CTRX concentrations in serum, sputum and urine were determined. The results obtained are summarized as follows: 1. Clinical responses to CTRX in a total of 29 cases with respiratory tract infections were excellent in 7 cases, good in 13, fair in 8 and poor in 1 with a response rate of 69.0%. 2. CTRX concentrations in serum, sputum and urine (total and free body) were determined in 3 cases after intravenous drip infusion of 2g CTRX. Peak levels in sputum were 2.6 to 7.8 micrograms/ml, and CTRX maintained high sputum levels for 12 to 24 hours after administration. PMID- 1890722 TI - [Dose calibration of aztreonam in pediatric patients by means of pharmacokinetic analysis]. AB - One of the current pharmacological problems with antibiotics is possible overdose among children of 7 years of age and older, when their dose was calculated on a per kg basis. In order to evaluate the difficulties, a pharmacokinetic analysis of aztreonam (AZT), which is a monocyclic beta-lactam antimicrobial agent, was undertaken in 2 groups consisting of 5 children of ages 1-6 and 5 older children of 7-15. Data from the younger children were fitted both to one- and two compartment models while those from the older age group perfectly were fitted to a two-compartment model. Using these fitted curve, a simulation dose study was carried out in order to see if we can find a clue for a better dose calibration for the older group of children. The results suggested that the dose of AZT in per kg basis for the older children can be reduced to 60% levels of the younger, that is, 60 mg/kg for the older in contrast to 100 mg/kg for the younger. PMID- 1890724 TI - [Placental transfer and pharmacokinetic parameters of flomoxef during the perinatal period]. AB - Flomoxef (FMOX), a new oxacephem with low MIC values against not only Gram negative bacilli (GNB) but also against Gram-positive cocci (GPC), was evaluated for its transfer into fetus, amniotic fluid, maternal milk, spinal fluid and urine during the perinatal period following a single intravenous drip infusion at a dose of 1 g for 30 minutes. The results obtained are summarized below. 1. High concentrations of FMOX were demonstrated in maternal serum, umbilical arterial serum and amniotic fluid with Cmax values of 48.0, 10.99 and 10.20 micrograms/ml, respectively. 2. Maternal urinary excretion rate was 65.4% in the first 6 hours after administration. 3. In contrast, maternal milk and spinal fluid levels were lower than 3 and 0.20 micrograms/ml, respectively. These results showed a good placental transfer of FMOX, which is very useful for various perinatal infections. No adverse effects were observed in mothers and neonates during the course of this study. PMID- 1890723 TI - [Study on flomoxef in the perinatal period]. AB - The placental passage and the the therapeutic efficacy of flomoxef (FMOX, 6315-S) were studied in patients in the perinatal period. A summary of the obtained results is as follows: 1. Concentrations of FMOX in maternal serum, umbilical cord serum and amniotic fluid obtained upon one-shot intravenous injections to 12 patients were compared with those obtained upon 1 hour drip infusions to 9 patients. It was found that the former means of administration gave higher concentrations that the latter. 2. Concentrations of FMOX in maternal serum, umbilical cord serum and amniotic fluid at 1 to 6 hours after administration through either method were all higher than MIC80's of recognized bacteria. 3. Clinical efficacies were evaluated in 10 patients with puerperal intrauterine infection, 7 patients with endometritis, 2 patients with pyelonephritis and 1 patient each with endo-cervicitis, amniotic fluid infection, mastitis and perineal wound infection. Clinical efficacies were excellent in 5 patients (21.7%), good in 17 patients (73.9%) and poor in 1 patient (4.4%), thus the overall efficacy rate was 95.7%. 4. Eradication of causative bacteria were obtained in all 8 cases tested, hence the eradication rate was 100%. 5. Mild diarrhea in 1 patient was the only side effect observed. No abnormal clinical laboratory test results were found in any patients. PMID- 1890725 TI - [Clinical studies on flomoxef in pregnant women with infections during the perinatal period]. AB - Clinical efficacies of flomoxef (FMOX), which is a newly developed oxacephem antibiotic, were evaluated in 14 cases of obstetric and gynecologic infections during the perinatal period. The results were excellent in 6 cases (42.9%) and good in 8 cases (57.1%). No side effects nor abnormal clinical laboratory test results were observed in mothers or neonates. Thus, FMOX appears to be a useful antibiotic for perinatal infections. PMID- 1890726 TI - [Clinical studies on flomoxef in the perinatal period infections]. AB - We conducted clinical efficacy and safety tests of flomoxef (FMOX, 6315-S) in the perinatal infections and obtained the following results. 1. A total of 25 patients was treated: 16 patients with intrauterine infections, 2 patients with pelvioperitonitis, 4 patients with urinary tract infections and 3 patients with other infections. FMOX was injected at a daily dose of 2-4 g for 3-15 days (6-60 g for total dose) by intravenous drip infusion, intravenous injection or their combination. 2. The clinical efficacy rate was 96.0% of 25 patients: excellent in 4 cases (16.0%), good in 20 cases (80.0%) and poor in 1 case (4.0%). Bacteriological effects obtained were: eradicated in 14/16 cases (87.5%) replaced in 3 cases. 3. There were no subjective or objective side effects, nor were any abnormal laboratory test values attributable to the drug. From these findings, we consider that FMOX treatment appears to obtain good clinical and bacteriological responses and in safe in perinatal period infections. PMID- 1890727 TI - [Pharmacokinetic and clinical studies of flomoxef in perinatal period]. AB - Pharmacokinetic and clinical studies of flomoxef (FMOX) in perinatal period were carried out and the following results were obtained. 1. Concentrations of FMOX in maternal serum, umbilical cord serum and amniotic fluid were determined subsequently to intravenous injection (4 cases) and intravenous drip infusion method (20 cases) of 1 g FMOX. Maternal serum levels were similar to those of healthy adults, and peak levels of umbilical cord sera and amniotic fluids were 12.0 micrograms/ml and 12.05 micrograms/ml, respectively, using intravenous drip infusion. The levels in amniotic fluids were higher than those in umbilical cord sera at 2 hours after treatment in either administration method. Parameters T 1/2 (beta) and AUC were 1.05 hours and 74.1 micrograms.hr/ml, respectively. 2. In the treatment of 4 cases with perinatal infection and in prophylaxis cases, clinical efficacies of FMOX were all good with 1 g twice daily treatment using intravenous drip infusion. No side effects nor abnormal laboratory test values due to the drug were observed in any cases. These results indicate that single intravenous drip infusion of FMOX 1-2 g twice daily is effective for the treatment and the prophylaxis of perinatal infections. PMID- 1890728 TI - [Studies on flomoxef in the perinatal period]. AB - Pharmacokinetic, bacteriological and clinical studies on flomoxef (FMOX) in the perinatal period were carried out with the following summary of the results. Antibacterial effects of FMOX on the growth of methicillin-resistant Staphylococcus aureus (MRSA, MIC 400 micrograms/ml), methicillin-sensitive S. aureus (MSSA, MIC 0.78 microgram/ml), Escherichia coli (MIC 3.13 micrograms/ml and MIC 0.20 microgram/ml) in amniotic fluid were determined and it was found that the activity of FMOX was enhanced in the amniotic fluid. FMOX rapidly penetrated into tissues and sera of pregnant women upon intravenous injection and its maternal serum concentrations reached their peak levels shortly after administration. Placental penetration of FMOX to the fetus was good and, after single intravenous injection of 1 g, the concentrations of FMOX in the umbilical cord serum and amniotic fluid exceeded MICs against major causative organisms of perinatal infections. These results indicate that single intravenous injection of FMOX 1 g twice a day is effective for the treatment and prophylaxis of perinatal infections. Injection of FMOX for the treatment of 14 cases of puerperal infections showed excellent clinical effectiveness with 100% clinical effect and 81.8% bacteriological response. No side-effect was observed in any case. All of these results suggested clinical usefulness of FMOX in the perinatal period. PMID- 1890729 TI - [Pharmacokinetic and clinical studies on flomoxef in perinatal period]. AB - Pharmacokinetic and clinical studies on flomoxef (FMOX) in the perinatal period were carried out. The results are summarized as follows. 1. The concentration of FMOX in umbilical cord serum was about 10 micrograms/ml in about 30 minutes after 1 g one shot intravenous injection. Amniotic fluid concentration was 7 micrograms/ml in 41 minutes after administration. By 1 hour intravenous drip infusion, FMOX concentration in umbilical cord serum was about 5 micrograms/ml in 2-3 hours after administration. Amniotic fluid concentration of about 20 micrograms/ml was found in 1 case. 2. FMOX 1-2 g x 2-3/day was given by intravenous drip infusion to 7 cases of perinatal infection for 4-26 days. Clinical efficacies were evaluated a good for all cases. Neither side effect nor abnormal laboratory test value was observed. Consequently, FMOX was considered to be highly effective and safe for its clinical use in perinatal period infections. PMID- 1890730 TI - [Pharmacokinetic and clinical studies on flomoxef in the perinatal period in obstetrics and gynecology]. AB - Pharmacokinetic and clinical studies on flomoxef (FMOX) in the perinatal period in obstetrics and gynecology were performed and the results obtained are summarized as follows: 1. Concentrations of FMOX in maternal serum, umbilical cord serum and amniotic fluid were determined after intravenous injection of 1 g. The maternal serum concentration was 41.9 micrograms/ml at 16 minutes after administration, and gradually decreased thereafter to 1.36 micrograms/ml at 5 hours 19 minutes. The concentration of FMOX in umbilical cord serum was 17.5 micrograms/ml at 16 minutes after administration, then gradually decreased thereafter, was slightly higher than that in maternal serum after approx. 3 hours and was 2.88 micrograms/ml at 5 hours 19 minutes. The amniotic fluid concentration was 0.31 micrograms/ml at 16 minutes after administration, increased to 7.85-15.8 micrograms/ml at approx. 3 hours, and gradually decreased while maintaining relatively high levels. 2. One or two grams of FMOX were given by intravenous drip infusion twice daily to 17 patients with perinatal infections for 5 to 7 days. Clinical efficacies were evaluated as excellent in 7 cases and good in 10, suggesting that FMOX was effective in all cases. No subjective side effects were observed in any of the 17 patients. As to abnormal laboratory findings, a minor degree of elevation of GPT was observed in 1 patient and that of GOT.GPT in 1. No other abnormal changes in laboratory examinations were observed. Considering the above results, we conclude that FMOX is a useful antibiotic in perinatal infections. PMID- 1890731 TI - [STAPHYOGRAM, a new rapid identification kit for the aerobic, gram-positive, catalase-positive cocci--application of fluorometric microplate hybridization for the pre-identification of 386 isolates used]. AB - A new simplified test kit, STAPHYOGRAM plate, was developed for 4-hr identification of aerobic, Gram-positive and catalase-positive cocci. The plate has 18 wells, in which different dehydrated substrates and nutrients are fixed. An 18-hr agar-culture suspension of a test strain with a turbidity of McFarland No. 4 was distributed into all wells in 50-microliters quantities. After 4-hr incubation at 37C, the profile number was obtained by summarizing positive reactions. The ability of the plate to differentiate the type strains of the 30 species of the three genera in the family Micrococcaceae was confirmed. These three genera are Staphylococcus, Micrococcus and Stomatococcus. The applicability of the fluorometric microplate hybridization technique to identification of aerobic, Gram-positive and catalase-positive cocci was confirmed by homologous hybridization among the type strains of the 30 species. Thus, 386 isolates of human and animal origin were pre-identified by microplate hybridization and used for evaluating the STAPHYOGRAM plate. Of the 236 profile numbers thus obtained with the 386 isolates, 218 (92.4%) were species-proper each and all for the 15 species of Staphylococcus and Stomatococcus mucilaginosus. A total of 342 (88.6%) of the 386 isolates were given such profile numbers, and were identified without any additional test. Among the 15 species identified primarily by the results of STAPHYOGRAM plate culture, S. caprae, S. lugdunensis, S. gallinarum and S. delphini were validly published after Approved Lists of Bacterial Names. The identified strains of S. caprae (48), S. haemolyticus (46), S. capitis (35) numbered between those of S. epidermidis (67) and S. saprophyticus (31). Profile numbers common to two species were seven (27 strains) and that to four species was one (17 strains). These 44 strains were identified with one to three additional tests. From these results, we were convinced that the STAPHYOGRAM test plate is useful for the rapid identification of members of family Micrococcaceae. By compiling STAPHYOGRAM plate data on genetically identified strains, an exclusive list of profile numbers will soon be prepared for perfection of the kit. PMID- 1890732 TI - [Expression and extracellular release of transferrin receptors on erythropoiesis]. AB - One of the most important factors for the proliferation and hemoglobin synthesis of erythroid cells is iron atom. This atom is tightly bound to serum transferrin (Tf) and is taken up by erythroblasts and reticulocytes through transferrin receptor (TfR). Both Tf and TfR are reutilizable and have roles for the efficient intracellular accumulation of iron. In addition to the reutilization (recycling), the expression of TfR is also regulated by cytoplasmic iron concentration; the increase of iron downregulate the synthesis of TfR at the translational level and vice versa. This mechanism was recently explained by the binding between "iron responsive element (IRE)" in the 5' end of TfR mRNA and IRE binding protein by a transacting manner. Johnstone et al, and we found that TfR was externalized from sheep reticulocyte and human erythroleukemia cell, K562, respectively. Furthermore, we confirmed that this shed TfR was detected in blood and concluded that the quantitation of TfR in serum is a useful index for evaluating the erythropoiesis. The serum TfR was increased in iron deficiency anemia, hemolytic anemia and polycythemia and was decreased in aplastic anemia. In renal anemia, it was increased after the administration of erythropoietin (Epo). By the in vitro liquid culture of peripheral blood stem cells using interleukin 3 and Epo, it was found that soluble TfR was derived from the erythroblasts during the maturation process. PMID- 1890733 TI - [Molecular analysis of thalassemia]. AB - Molecular analysis of gene structure using PCR related techniques has been described. These techniques were applied to analysis of the beta-globin gene from Japanese individuals with beta-thalassemia. We found one promoter mutation, two splicing mutations, two frameshift mutations, one nonsense mutation. We also detected three different mutations within the third exon. They produced highly unstable globin variants, leading a dominantly inherited beta-thalassemia phenotype. Six of nine different mutations seem to originate in Japanese. Characteristics of molecular defects of Japanese beta-thalassemia was discussed in terms of malaria hypothesis. PMID- 1890734 TI - [Clinical significance of erythrocyte ferritin]. AB - Quantitative and qualitative evaluations of erythrocyte ferritin in 161 patients with RA and RAEB in MDS, AML, CML, PV, PA, HS, IDA, chronic liver disease and alcoholic liver disease were carried out. Mean erythrocyte ferritin levels of patients with RA, AML, PA, HS and alcoholic liver disease were increased compared with normal subjects. On isoelectric focusing analyses (IEF), erythrocyte ferritin in normal subjects were detected between pI 5.1 and 5.7. In the cases of RA, pI ranges of erythrocyte ferritin may be divided into three groups, acidic, neutral, basic shift on IEF respectively. In these groups, the more acidic the ferritin shift, the higher the proportion of morphological abnormalities of the erythroid precursors in the bone marrow was observed. In patients with AML (M2, M3, M4), little difference was found among these three subtypes, and all of the cases showed similar pattern with normal subjects on IEF. The ferritin from IDA showed low levels and slight basic shift compared with normal subjects on IEF, and these features were also found in patients with CML (chronic phase) and PV. After iron supplementation, marked increase of acidic ferritin was detected on IEF indicating an intermediate store for iron destined for haem synthesis. It was clear that the stainable iron in liver parenchymal cells were found at erythrocyte ferritin concentration 20 ag/cell or over in patients with chronic liver disease. Measurement of erythrocyte ferritin concentration is a helpful method for evaluating iron deposition in hepatocyte non-invasively. From these results it is considered that quantitative and qualitative analyses of erythrocyte ferritin are very useful for evaluating erythropoiesis as well as iron metabolism. PMID- 1890735 TI - [Carbohydrate auto-antigens in auto-immune hemolytic anemia]. AB - Anti-erythrocyte antibodies which appear in the sera of patients with auto-immune hemolytic anemia frequently recognize carbohydrate auto-antigens. Most of cold agglutinins are known to recognize the Ii-antigens, and Donath-Landsteiner antibodies which appear in patients with paroxismal cold hemoglobinuria are almost exclusively directed to the P-antigen. These carbohydrate auto-antigens are strongly expressed in various tissues and organs other than erythrocytes, and behave as differentiation- or developmental-antigens, in both humans and mice. The study of nucleotide sequences of human and murine anti-Ii antibodies shows that these antibodies share a highly homologous antigen-binding site in their VH regions. These results indicate that the carbohydrate auto-antigens in autoimmune hemolytic anemia are evolutionally conserved developmental antigens, and suggest that the immunoglobulin genes which encode variable regions of the auto antibodies directed to these antigens are also conserved evolutionally. PMID- 1890736 TI - [Altered metabolism of membrane glycosphingolipids in erythrocytes of paroxysmal nocturnal hemoglobinuria]. AB - Paroxysmal nocturnal hemoglobinuria (PNH) is currently accepted to be a stem-cell disorder of a clonal nature with increased susceptibility to autologous complement attack. Consequent hemolytic feature has been partly explained by lack of complement regulatory membrane proteins such as decay-accelerating factor (DAF) or C8-binding protein that anchored to membrane via glycosyl-phosphatidyl inositol (GPI) lipids. Recent reports suggest essential PNH lesion is the synthetic defect of sugar moiety of the PI-anchor. In PNH, the abnormal expression of C3b/C4b receptor (CRI) glycoproteins, or glycophorin-alpha have been also pointed out. These altered expression of glycoproteins and glyceroglycolipids, especially in the carbohydrate structures, prompted us to analyze biochemically the membrane glycosphingolipids as one of major glycoconjugates in PNH. As results, PNH erythrocytes showed altered metabolism of gangliosides in comparison to control erythrocytes from healthy donors. IV6 NeuAc nLc4 Cer and highly polar gangliosides variably disappeared in PNH erythrocytes, partly due to impaired sialylation of glycolipids. These results suggest metabolic disorder of carbohydrates of membrane glycoconjugates as a new aspect of PNH. PMID- 1890737 TI - [Diagnosis of stem cell leukemias in view of phenotypic and genotypic analysis]. AB - To identify the biological characteristics of so called stem cell leukemia (SCL), of which leukemic blast cells should be derived from pluripotent stem cells, immunophenotypical and genotypical analysis and response to several hematopoietic cytokines were studied in 272 cases with acute de novo leukemia. In 132 cases with acute myelogenous leukemia (AML), some cases of CD19+ and/or CD7+ AML were considered as SCL. In cases with myeloperoxidase negative acute lymphoblastic leukemia (ALL), cases of CD7 + CD1 - CD3 - CD4 - CD8 - My-Ag (myeloid antigens) +ALL, considered as those of T-precursor ALLs, and cases of HLA-DR + CD19 + CD20 My-Ag + ALL, considered as those of B-precursor ALLs, were though to be SCL. We did not think the cases of ALL with dual genotype to be SCL, since dual genotype could not be considered as sings of ability to differentiate to multilineage but as products of the process of active V-DJ rearrangements of Ig heavy chain gene. PMID- 1890738 TI - [Rearrangement and expression of bcr-abl genes in CML and ALL]. AB - We have carried out the molecular and cell-biological analysis on Ph1-positive leukemias in this study. Five out of nine Ph1-positive ALL cases showed molecular rearrangement within the classical bcr sequence (or M-bcr), similar as those in 47 CML cases. We examined 4 cases of Ph1-positive ALL presenting no rearrangement of M-bcr and found that, in 2 of 4 cases, one showed the breakpoint in a 5 kb segment of the bcr gene first intron (bcr-2) and the other in bcr-1, 16 kb upstream of bcr-2. Ph1-positive ALL frequently showed biphenotypical or biclonal phenotypes of myeloid and lymphoid lineages. Furthermore, we demonstrated the ability of two Ph1-positive ALL cell lines to differentiate into monocytic lineage in vitro, thus suggesting the possibility that these Ph1-positive ALL cells might reside on the stage of multipotent stem cell along the hematopoietic cell differentiation. Two out of 31 CML cases showed the mutations of the ras genes by the polymerase chain reaction; one case in the crisis phase and the other in the chronic phase. However, no mutations of the fms genes was detected. Two cases in the crisis phase of 24 CML patients (11 cases in the chronic phase and 13 cases in the crisis phase) contained rearrangements of the p53 gene by Southern analysis. Furthermore, the transcriptional alteration was found in 2 CML BC and 2 CML-BC derived cell lines' samples, suggesting a important role of the p53 gene in the transformation of CML into the crisis phase. PMID- 1890739 TI - [Analyses of T cell receptor and its clinical implications in T cell neoplasms]. AB - We studied gene rearrangement and expression of immunoglobulin heavy (IgH) chain, T cell receptor (TCR) beta, gamma and delta chains in neoplastic T cells from patients with leukemia and lymphoma. Rearrangements of TCR beta and gamma chain genes were observed in most of T cell neoplasms. TCR delta chain gene rearrangements or deletions were detected in all 77 T cell neoplasms; 6 of 9 CD3- T cell neoplasms showed rearrangement, whereas biallelic deletion of TCR delta chain gene was the most common pattern in CD3+ T cell neoplasm (65 of 68 patients). One patient with CD3- T cell leukemia had TCR delta chain gene rearrangement with a germline configuration of TCR beta, gamma and IgH chain genes. TCR gamma and delta chain gene transcripts were detected in most of the CD3- T cell neoplasms, whereas mature TCR alpha and beta chain mRNA were demonstrated in the majority of the CD3+ T cell neoplasms. In 6 patients with CD7+ CD3- CD4- CD8- MPO- leukemia, only 2 patients had rearrangements and weak expressions of IgH, TCR gamma and delta chain genes. We also present two cases of double negative (CD3+ CD4- CD8-) leukemia; one is TCR gamma delta bearing LGL, the other is TCR alpha beta bearing ATL. These results suggest that most of T cell neoplasms preserve a pattern of genotypic and phenotypic expression reflecting their developmental pathways and differentiation levels of TCR bearing normal T cells. PMID- 1890740 TI - [Antigen receptor gene analysis in lymphoid malignancies--a study using the polymerase chain reaction]. AB - A leukemia line KOPN30bi was established from a patient of acute lymphoblastic leukemia with Philadelphia chromosome. The clonal rearrangement of the immunoglobulin heavy chain gene was identical between KOPN30bi and the predominant clone in the fresh sample (S1) from which KOPN30bi was established, indicating that they are of the same clonal origin. The study of the T cell receptor (TCR) genes including TCR beta, gamma, delta loci showed none of these loci was identical between KOPN30bi and S1. The result of the TCR delta region analysis which was rearranged on one of the alleles in KOPN30bi and was deleted on both alleles in S1, however, indicated KOPN30bi was not a derivative of S1. Polymerase chain reaction, using oligonucleotide probe corresponding to the N region sequence of V gamma-J gamma juncture of KOPN30bi, indicated that only one % of the blast cells in S1 corresponded to KOPN30bi. These studies indicated that the predominant clone in the fresh sample, although it occupied more than 99% of the blasts, did not represent the characteristics of the target cell for leukemogenesis, and furthermore that the leukemogenic molecular mechanisms such as P190 type BCR/ABL translocation are not enough to freeze the differentiation of the target cell. PMID- 1890741 TI - [bcl-2 gene in B cell lymphoma]. AB - In t(14;18) lymphomas, bcl-2 gene is activated by the juxtaposition of immunoglobulin (Ig) gene. The fused bcl-2-Ig gene generates chimeric mRNAs which consist of bcl-2 at 5' side and Ig at 3' side. Chimeric mRNA does not disrupt the bcl-2 coding frame of 239 amino acid polypeptide. Activated bcl-2 gene introduced in normal B lymphoblastoid cells (LCL) demonstrated an increased cloning efficiency in soft agar but failed to confer tumorigenicity to LCLs as a single agent. bcl-2 gene rearrangement in Japaneses B cell lymphoma was studied and found that 10 out of 32 cases of follicular lymphoma (31%) and 5 out of 56 cases of diffuse lymphoma (9%) were rearranged, suggesting less frequency of B cell lymphoma, particularly follicular lymphoma in Japan is partly due to less bcl-2 involvement than American cases. Three cases out of 15 cases with bcl-2 rearrangement demonstrated a unique pattern of rearrangement. Two cases of the three were analysed and found that both cases were translocated at the later step than DH-JH joining of Ig rearrangement. Thus, bcl-2 translocation in Japanese B cell lymphomas might occur at the later stage of B cell development, when compared with that in American cases. Less involvement of bcl-2 in Japanese B cell lymphoma may be explained by low susceptibility to bcl-2 rearrangement at the step of DH-JH recombination. PMID- 1890742 TI - [B-CLL and bcl-2 gene]. AB - Most of human follicular lymphomas (approximately 90% in U.S.A. or approximately 30% in Japan) possess the t(14; 18) chromosome translocation that directly involves the IgH locus on chromosome 14 and the bcl-2 gene on chromosome 18. The t(14; 18) chromosome translocation occurs nearly exclusively at two hot spots, a major breakpoint clustering region (mbr) within the 2nd exon noncoding region and the minor breakpoint clustering region (mcr) within the 3' flanking region of the bcl-2 gene. Here we show that the rearrangement of the bcl-2 gene occurs in a significant fraction (approximately 10%) of B-CLL. All of the rearranged bcl-2 genes were juxtaposed with Ig lambda or Ig kappa genes, implying that the bcl-2 gene is preferentially linked to the IgL genes in CLL. PMID- 1890743 TI - [Isolation of a novel candidate proto-oncogene involved in human lymphoid neoplasm]. AB - The 14;19 translocation [t(14;19) (q32;q13)] is a recurring chromosomal translocation observed in leukemic cells of chronic lymphocytic leukemia showing prolymphocytic transformation. We have cloned the breakpoint junction of the translocation and identified a new gene, bcl-3, on the chromosome band 19q13 adjacent to the breakpoint. The translocation occurred at the switch region of the alpha constant locus of the immunoglobulin heavy chain gene and the upper stream of the bcl-3 gene, resulting in a head-to-head recombination between the two genes on the 14q+ chromosome. The bcl-3 gene was highly expressed in the leukemic cells carrying the 14;19 translocation. The bcl-3 gene product contained repeat structures found in proteins involved in cell cycle control and cell lineage determination. These results suggest that the bcl-3 is a proto-oncogene that may contribute to the development of leukemias carrying the 14;19 translocation. PMID- 1890745 TI - [Non-Hodgkin's lymphoma of the nasal cavity and paranasal sinuses: clinicopathologic study of ten cases]. AB - Ten patients with non-Hodgkin's lymphoma originated in the nasal cavity (four patients) and in the paranasal sinuses (six patients) were treated mainly with irradiation and combination chemotherapy including adriamycin. According to the TNM AJC staging system, four patients were in stage T1-T2, and six patients were in stage T3-T4. Nine patients, other than one with stage IV (Ann Arbor) disease, achieved complete remission. Death due to lymphoma occurred in four patients, 4 to 39 months following diagnosis. Three of these patients developed systemic extranodal dissemination, and died in a short time after relapse. Death due to second malignancies occurred in two patients. One died of acute myelogenous leukemia, and the other died of colon cancer, 26 and 53 months after diagnosis, respectively. Four patients were alive and disease-free, from 23 to 68 months following diagnosis (median 40 months). Out of four patients who died of disease, three were in stage T3-T4, and one was in stage T1. Two patients with stage T1 originated in the nasal cavity were both alive and disease-free. Except for lymphomas with stage T1 originated in the nasal cavity, more intensive chemotherapy should be instituted in an attempt to achieve better disease-free survival. PMID- 1890744 TI - [Clinical trial of alpha-interferon (human lymphoblastoid interferon) in combination with VCAP chemotherapy in multiple myeloma]. AB - We compared the effect of combined natural interferon-alpha (HLBI)/VCAP chemotherapy with VCAP chemotherapy alone on multiple myeloma. Sixteen previously untreated patients with multiple myeloma were treated with a combination of IFN alpha and VCAP chemotherapy; nine of them were treated with HLBI-VCAP (I) regimen (HLBI 3 x 10(6) units/day, daily, 56 days) only for induction chemotherapy, and seven with continuous HLBI-VCAP (II) regimen (HLBI 3 x 10(6) units/day, twice a week) both for induction and maintenance chemotherapy. Thirty-one control patients were treated with a VCAP regimen only. HLBI-VCAP (II) regimen exhibited an 85.7% (6/7) response rate, while VCAP and HLBI-VCAP (I) regimen showed 74.2% (23/31) and 77.8% (7/9) response rates, respectively. The median duration of survival was 43 months in the control group, greater than 44 months in HLBI-VCAP (I) group and greater than 45 months in HLBI-VCAP (II) group. No significant difference in survival duration has yet been observed between the VCAP group and HLBI-VCAP groups. We conclude that continuous, long-term combination therapy with HLBI and VCAP regimen for induction and maintenance therapy may be most effective, and found that intensive HLBI-VCAP regimen, for only remission induction therapy, was not more effective than VCAP regimen alone. PMID- 1890747 TI - [No rearrangement of the breakpoint cluster region in two juvenile chronic myeloid leukemia]. AB - We performed cytogenetic studies and breakpoint cluster region (bcr) rearrangement analysis in two cases of juvenile chronic myeloid leukemia (JCML) which is special type of chronic myeloid leukemia (CML). Case 1 (8-month-old male) and case 2 (3-month-old female) showed clinical and hematologic manifestations similar to CML. Each of case 1 and 2 had normal karyotype and no bcr rearrangement. These findings suggest that JCML is a different heterogeneous disorder from that of adult CML. PMID- 1890746 TI - [A remarkable effect of alpha-interferon in a case of angioimmunoblastic lymphadenopathy with dysproteinaemia (AILD) refractory to steroids and combination chemotherapies]. AB - We experienced a remarkable effect of recombinant interferon alpha 2a (alpha-IFN) in a case of angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) which was refractory to steroids and combination chemotherapies. A 62 year-old woman was admitted because of high grade fever and extreme swelling of cervical lymph nodes. Poly-clonal hypergammaglobulinemia and plasma cell-like atypical lymphocytosis in the peripheral blood were demonstrated. Cervical lymph node biopsy disclosed histology of AILD. She initially responded well to prednisolone. Three months later, AILD relapsed in spite of prednisolone treatment. She received combination chemotherapies and responded well again. Seven months later, she became refractory to these combination chemotherapies. Consequently, we tried alpha-IFN (3 million units/day given intramuscularly). She became afebrile on the next day, and lymph nodes swelling gradually disappeared. She has been free from the disease for more than three months. PMID- 1890748 TI - [Nuclear DNA analysis of benign skin tumor and carcinoma in site developed from keratinocyte]. AB - To know the variation of DNA contents of seborrheic keratosis, keratoacanthoma, actinic keratosis, and Bowen's disease, cytophotometric assay was used. As the results, following findings were obtained. 1. DNA index of actinic keratosis was higher than those of seborrheic keratosis and keratoacanthoma. 2. DNA index of Bowen's disease was higher than that of seborrheic keratosis. 3. Polyploid cell population (greater than 6C) of keratoacanthoma was higher than that of seborrheic keratosis. 4. Polyploid cell populations (greater than GC) of carcinoma in site (actinic keratosis, Bowen's disease) were higher than that of keratoacanthoma . These date suggested that polyploid cell population and DNA index reflect grade of malignancy of tumor developed from keratinocytes. A clinic keratosis and Bowen's disease revealed almost the same DNA pattern. And the difference of polyploid cell population of keratoacanthoma++ ++ and seborrheic keratosis suggested the difference of the biological activity of them. PMID- 1890749 TI - [Nuclear DNA contents in the cells of squamous cell carcinoma. III. Separation and analysis of polyploid cells]. AB - In order to reveal the cytological nature of polyploid cells, the cell suspension of squamous cell carcinoma was separated into low density (1.050 greater than), intermediate density (1.050 to 1.088), and high density (1.988 greater than) fractions, by density gradient centrifugation. The DNA content of the tumor cells in each fraction were measured on the smear specimens prepared by Giemsa's staining and Feulgen's stainings. As the results, it was found that the cells showing high NC ratio and having high DNA content were observed in the high density fraction. However, there was no specific relationship between the nuclear contour index and density of the tumor cell. PMID- 1890750 TI - [Prenatal diagnosis of lethal junctional epidermolysis bullosa by fetal skin biopsy]. AB - A 22-year-old woman, whose first infant had died of lethal junctional epidermolysis bullosa (JEB), requested prenatal diagnosis for her third pregnancy. At 20 weeks gestation, fetal biopsy was performed under direct vision by fetoscopy. A semithin section of epon-embedded skin showed dermo-epidermal separation at the light microscopic level. Electron microscopy revealed the site of separation to be within the lamina lucida of the epidermal basement membrane (EBM). Indirect immunofluorescence on a 5 microns cryostat specimen of skin showed a complete absence of GB3 monoclonal antibody immunostaining at the EBM compared with a control 18 week old normal fetal skin sample. The diagnosis was therefore made that the fetus was affected with lethal JEB and a prostaglandin termination performed. The diagnosis was confirmed by further studies on the aborted fetus. 54 cases of prenatal diagnosis of various types of epidermolysis bullosa performed at Institute of Dermatology over the last 10 years are briefly reviewed. Several social and practical problems to launch prenatal diagnosis in Japan are also discussed. PMID- 1890751 TI - [Skeletal alterations associated with long-term etretinate therapy]. AB - Radiographic skeletal examinations were performed in sixteen adult patients who had received etretinate therapy for various keratinizing disorders (psoriasis vulgaris 13, pustular psoriasis 2, pustulosis palmoplantaris 1) over periods ranging from 0.7 to 4.5 years. The total dose of etretinate ranged from 5.1 to 36.5 g. In these patients, the frequency and the degree of skeletal alterations including hyperostosis, calcification of ligaments and periosteal thickening was found to be higher than that in age- and -sex matched, nontreated controls. Furthermore, almost all of these patients were asymptomatic and revealed no abnormalities in laboratory data, including levels of serum calcium, inorganic phosphate and alkaline phosphatase. It is necessary for patients who are undergoing long-term etretinate therapy to be examined regularly for such skeletal abnormalities. PMID- 1890752 TI - [Two cases of L-tryptophan ingestion induced eosinophilia-myalgia syndrome]. AB - Eosinophilia-myalgia syndrome (EMS), a new connective tissue disease was reported and named in 1989 from New Mexico, U.S.A. L-tryptophan has been suspected as the causative agent of EMS. This L-tryptophan was made in Japan, but no definite case of EMS has been reported in Japan. We report 2 patients with EMS. A 72-year-old woman and a 74-year-old woman, who had been treated with oral L-tryptophan 1 g/day for 4 and 5 months by the same doctor simultaneously. The clinical courses of the two cases were similar. A diffuse erythema and swelling appeared on the arms and spread over the whole body. The skin lesions turned into lustrous sclerosis. Eosinophilia was remarkable in the early stage. ANA, DNA anti-body and ENA antibodies were all negative. Neurological examination revealed a mild peripheral neuropathy. No sclerodactylia and no Raynaud's phenomenon in our cases are characteristic findings in EMS. The simultaneous onset of two cases using the same drug at the same time implicates the close relation of L-tryptophan ingestion to EMS. PMID- 1890753 TI - [Experimental study of the relationship between in vitro binding activity and in vivo tumor accumulation of radiolabeled anti-CEA monoclonal antibodies]. AB - The immunoreactivity and affinity of seven kinds of monoclonal antibody raised against human gastric cancer (MKN-45) secreted carcinoembryonic antigen (CEA) were determined with the method of cell binding assay in vitro. Tumor localization and biodistribution of radiolabeled antibodies were performed in athymic mice implanted MKN-45 xenografts. Results obtained were as follows: 1) The affinity constant of CEA-specific three antibodies (1A4, 1B2, 4H11) was the same approximately, whereas the immunoreactivity found to be quite different among them. While CEA-nonspecific four antibodies (7D1, 6C7, 2C3, 5H7) showed the much higher affinity constant than that of the former. 2) In an animal model on tumor localization and biodistribution studies, CEA-specific antibodies obtained more highly tumor targeting and cleared more rapidly from the blood and non-tumor organs than CEA-nonspecific antibodies did, so that tumor to nontumor ratios was increased. 3) In this model system it is the immunoreactivity preparation of antibodies that improved tumor targeting and tumor activity retention, on the other side, the affinity constant of antibodies were associated with rapid clearance from the blood and non tumor sites. In conclusion, this studies would also be beneficial for practical use and clinical application of radiolabeled monoclonal antibodies. PMID- 1890754 TI - [Examination of endoscopical ultrasonography (EUS) on carcinoid tumors of gastrointestinal tract]. AB - In order to clarify the usefulness of EUS in the diagnosis of gastrointestinal carcinoid tumor, we examined 15 patients, who had carcinoid tumors of gastrointestinal tract (stomach: 5, duodenum: 2, rectum: 8), on the diagnosis in quality and depth by comparing endoscopical ultrasonography (EUS) with resected specimen. Carcinoid tumors of gastrointestinal tract were detected as homogenous hypoechoic tumors with sharp border in all site by EUS. Especially, it was characteristic that 14 of the 17 lesions (82%) which invaded into submucosa were mainly located in the third layer, and the second layer covered the tumor at the foot, and near the top, it touched the tumor and got indistinct. We decided the depth of invasion by comparing the hypoechoic tumor with normal structure of 5 layers. The accuracy rate was 88%. In conclusion, EUS was thought to be useful in the diagnosis and choice for treatment of carcinoid tumors of gastrointestinal tract. PMID- 1890755 TI - [Long-term prognosis of Crohn's disease]. AB - Two hundred and three patients with Crohn's disease seen at our clinics and affiliated centers from April 1973 to August 1988 were followed for 4.4 +/- 3.2 years (mean +/- SD), in order to evaluate the prognosis of Crohn's disease in Japan. These 203 patients (142 males and 61 females) fulfilled the following criteria; 1) they have been followed at the outpatients clinic for more than six months or 2) they have been admitted to us for more than a month. Of these, 83 (40.9%) had ileitis, 60 (29.6%) ileocolitis, 25 (12.3%) colitis, 15 (7.5%) miscellaneous types and the remaining 20 (9.9%) had undergone bowel resection. Cumulative survival rate and cumulative probability of surgery were calculated by life table method. Cumulative survival rate in these patients was compared with expected survival rate of sex and age matched general population. Cumulative survival rates five and ten years after diagnosis were 98.9% and 98.9%, respectively. There were no significant differences in the survival rates between two groups. Cumulative probability of surgery five and ten years after onset of symptoms were 16.2% and 39.1%, respectively. Cumulative probability of surgery five and ten years after diagnosis were 25.9% and 46.9%, respectively. From these results, the prognosis of Japanese patients with Crohn's disease appears to superior to that in European and American literatures. PMID- 1890756 TI - [Ulcerative colitis and pregnancy]. AB - The relationship between ulcerative colitis (UC) and pregnancy was studied in 83 cases (124 deliveries). The results were as follows: 1) In women with UC, there was no significant difference in fertility compared with the general population. 2) The existence of UC and treatment of UC during pregnant period had no significant adverse effects for the course of pregnancy. 3) In the 17 out of 36 pregnancies with inactive UC at the onset of pregnancy suffered relapses. Relapse rate in same patients in the pregnant period was significant higher than that in the non-pregnant period. 4) First attack of UC developing in 12 cases during pregnancies or the puerperium, the onset being commonly in the first trimester. UC developing during pregnancy was especially severe in other patients. We concluded that the relapse rate of UC is high during pregnant period, however, the course of pregnancy is not affected with UC. PMID- 1890757 TI - [Influence of estradiol and testosterone on carbon tetrachloride-induced liver damage in the rat]. AB - The aim of the study was to know influences of estrogen and testosterone on carbon tetrachloride-induced liver damage in male Wistar rats. One hundred and two rats were divided into following six groups on the basis of the treatment: olive oil as control (O), carbon tetrachloride (0.1 ml/100 g, C), estradiol benzoate (0.1 mg/100 g, E), testosterone propionate (5 mg/100 g, T), C + E and C + T, in which each drug was intraperitoneally injected twice per week for consecutive 12 weeks. In the C + E group, decreases in serum albumin level at the 4th week and total cholesterol level at the 8th week seemed to be suppressed. And fibrotic change and fatty change were weak on the histological observation. However, hepatocellular hyperplasia was observed in 40% cases after the 8th week. On the flow cytometry analysis of the liver at the 4th week, an enhancement of hepatocellular proliferation was shown. Survival rate of the C + E group rats was lower than C group rats. On the other hand, in the C + T group, liver injury occurred in the same grade as C group, and the survival rate was worst among all six groups. These results suggest that simultaneous administration of estrogen with carbon tetrachloride could reduce hepatic injury, though it might cause hepatocellular hyperplasia. PMID- 1890758 TI - [An immunohistopathological study on intrahepatic distribution of HBeAga/b in biopsied chronic type B hepatitis]. AB - In order to evaluate the role of a expression of HBV-associated, we investigated histological and cytological distribution of HBeAga, HBeAgb, and HBcAg by immunoperoxidase procedure using monochronal antibodies. Materials submitted for this study were needle biopsied specimens obtained from 41 chronic carriers and serial paraffin sections were used for the immunohistological study. The localization of HBeAga/b antigens was limited in hepatocellular nuclei, and hepatocellular cytoplasm was HBeAg negative, HBeAg was detected in 11 cases (33%) of 33 cases with chronic active hepatitis (CAH) and in 5 cases (63%) of 8 cases with chronic inactive hepatitis (CIH). Among the HBeAg positive 16 cases, HBeAgb was demonstrated in 15 cases, however, HBeAga was revealed only each one case of CAH and CIH, respectively. Most of HBeAg positive cells were distributed in the peripheral zone of the hepatic lobules while the positive cells were found in central to midzonal zones of 3 cases CAH and one case of CIH. All in histopathologically HBeAga/b positive cases were also HBeAg positive serologically. On the other hand, in HBeAg sero-positive patients, histological positive rate of HBeAga/b was in 33% in CAH and 50% in CIH. PMID- 1890759 TI - [Angioarchitecture of the lower esophagus in portal hypertension]. AB - In order to clarify the angioarchitecture of the palisade zone in the lower esophagus for portal hypertensive cases, we examined the thirty untreated autopsy cases of portal hypertension. At autopsy, barium added gelatin was injected from gastric coronary vein of the gastric wall and we observed them histologically and histometrically. 1) In portal hypertension, the palisade zone has increasing veins running in the submucosa, which veins belonged originally to the lamina propria. 2) A difference in angioarchitecture is present between the palisade and truncal zones. 3) The palisade zone in esophageal varices was classified into two types of angioarchitecture by Hashizume. Our 30 cases were composed of 22 cases with palisading type and of 8 those with bar type. The later showed well developed varices. PMID- 1890760 TI - [Prospective controlled study of elective sclerotherapy plus oral propranolol for prevention of recurrent bleeding in cirrhotics with recent variceal hemorrhage]. AB - In a prospective, randomized controlled trial, 43 patients with cirrhosis and variceal hemorrhage were allocated after control of the bleeding to treat by elective sclerotherapy alone (n = 23) or by oral propranolol after elective sclerotherapy (n = 20). The dose of oral propranolol was based on a reduction of the resting pulse rate by 25%. The end points of the study were rebleeding or death. Both treatment groups were comparable with respect to origin and severity of liver disease, size of esophageal varices and portal pressure at entry. The mean follow up was 27 +/- 19 months for all patients. Patients treated sclerotherapy alone had more rebleeding (n = 11) did than those in the sclerotherapy plus propranolol (n = 3). The cumulative percentages of patients free of rebleeding 1 and 2 years after inclusion were 77 and 66% in sclerotherapy alone, and 100 and 85% in sclerotherapy plus propranolol; the difference between the two groups was significant. No statistically significant effect on mortality was seen. These data support that oral propranolol after sclerotherapy reduces the risk of recurrent bleeding in cirrhotics treated elective sclerotherapy. PMID- 1890761 TI - [A case of adenocarcinoma of the stomach associated with SIADH]. PMID- 1890762 TI - [A large gastric tumor composed of adenoma and carcinoma with rich Paneth cells]. PMID- 1890763 TI - [A case of chronic idiopathic intestinal pseudoobstruction and a review of literature in Japan]. PMID- 1890764 TI - [A case report of primary duodenal leiomyoblastoma]. PMID- 1890765 TI - [A case of biloma induced by spontaneous rupture of gallbladder]. PMID- 1890766 TI - [A case of pancreatic ascites with skin lesions and elevated serum CA125]. PMID- 1890767 TI - [A case of stenosis of the pancreatic duct due to periductal lymphocytic infiltration]. PMID- 1890768 TI - [A case report of thrombosis in portal and splenic vein due to alcoholic pancreatitis]. PMID- 1890769 TI - [Immunohistochemical localization of ethanol-inducible P450 (II E1) in the human upper gastro-intestinal tract]. PMID- 1890770 TI - [Most adenocarcinomas, arising in gastric hyperplastic polyps, show organoid growth of the pyloric-type mucosa]. PMID- 1890771 TI - [Analysis of maximal expiratory flow-volume curves--visual evaluation and quantitative evaluation]. AB - Maximal expiratory flow-volume (MEFV) curves have been utilized in the diagnosis of chronic obstructive lung diseases, in the survey of air pollution, and in studies of respiratory functions in school children. Indices for the lower lung volumes of MEFV curves have been used in statistical analysis or individual evaluation because of their effort independence, while indices for higher lung volumes of MEFV curves, which were considered to be effort-dependent, have not been used. A few reports using indices for higher and lower lung volumes have been described because the indices for higher lung volumes are as reproducible to the maximal expiration as those for lower lung volumes. Recently, MEFV-type analysis has been studied and this analysis has been useful in assessing the effects of smoking on MEFV curves, or in assessing subjects with nasal allergies or those with prior nasal allergies. From the aspects of hygiene, this review mainly describes MEFV-type analysis and the quantitative analysis of discriminant analysis. PMID- 1890772 TI - Effects of physical exercise and cold stimulation on serum testosterone level in men. AB - The concentrations of testosterone (TS) and other related hormones in serum were examined before and after physical exercise with a bicycle ergometer (90 Watts, 20 min.) and a cold water stimulation in 32 19-year-old males. While exercising, the serum TS level significantly increased by 20.8% (p less than 0.05), the luteinizing hormone (LH) level by 3.6% (p less than 0.05) and noradrenaline (NA) level by 140.0% (p less than 0.01). During cold water stimulation, TS decreased by 10.0%, LH increased by 22.1% and NA decreased by 23.8%. Based on changes in hormone levels within the individual during the loads. there was a significant positive correlation coefficient (r) between TS and LH, and between TS and NA, with r (TS-LH) = 0.399 (p less than 0.05) and r (TS-NA) = 0.481 (p less than 0.05) for physical exercise, while r (TS-LH) = 0.403 (p less than 0.05) and r (TS NA) = 0.431 (p less than 0.05) for cold water stimulation, respectively. These results suggest that physical exercise increases TS level in serum by increasing LH and NA levels, but these tendencies were not found with cold water stimulation. PMID- 1890773 TI - [Studies on the massive flights of chironomid midges (Diptera: Chironomidae) as nuisance insects and plans for their control in the Lake Suwa area, central Japan. 1. Occurrence of massive flights of Tokunagayusurika akamusi]. AB - Adult Chironomidae (Diptera, particularly Chironomus plumosus and Tokunagayusurika akamusi) emerging from eutrophic lakes or polluted bodies of water in Japan have become intolerable because they pose a severe nuisance and cause economic problems. In the Lake Suwa area, massive flights of adult midges of T. akamusi have occurred frequently, and caused problems in the daily life of local residents or for the tourist business. The author tried to clarify the biological and hygienic problems involved in these massive flights. In order to control adult midges, the distribution of larvae in the lake, the period and quantity of emergence from water, the time of flight, and the dispersal range of T. akamusi midges were studied. The results obtained are as follows: 1. Larvae of T. akamusi are distributed over the whole lake, especially in the east and southeast part with high densities. Mean biomass was about 100 g wet weight/m2 in Lake Suwa. On the shore near these areas, dense swarms of adult midges were found. 2. Emergence of T. akamusi from Lake Suwa was observed at the end of September and lasted till the middle of November. The emergence peaked in the middle of October. The time of flight was mainly at 17: 30-19: 30. 3. The dispersal ranges of adult midges were confirmed with two methods, i.e. the ordinary light trap method and a questionnaire survey of 544 residents. The result obtained with the questionnaire survey was consistent with that of the light trap method and the questionnaire survey made it possible to collect information in a wider area than the usual one. 4. T. akamusi midges reached areas over 3 km from the lake, but more than 90 percent of the midges flew within 500 m of the lake's shoreline. However, even in the more distant places where there was a source of bright light there were many adult midges. 5. The wind (at 18: 30) was the main factor which expanded the dispersal range of adults. We observed that many adults appeared after a strong wind (6-7 m/s). 6. Many adult midges were collected by light trap at the top of a building with a height of 45 meters. PMID- 1890774 TI - [Studies on the massive flights of chironomid midges (Diptera: Chironomidae) as nuisance insects and plans for their control in the Lake Suwa area, central Japan. 2. Quantitative evaluations of the nuisance of chironomid midges]. AB - In order to make clear the present "nuisance" caused by chironomid midges around a eutrophic lake, a questionnaire survey of 249 leaders of the Hygiene Self governing Association of the cities of Suwa and Okaya and the town of Shimosuwa near Lake Suwa was conducted. The results are as follows: 1. More than 90% of the respondents had specific knowledge about the chironomid midge, but 40% of them didn't know about its role as a purifier in the lake. 2. More than 10% of respondents answered that they were "can not able to stand any more" massive flights of chironomid midges, and about half of them lived within 500 m of the lake shore. The damages "nuisances" were "running laundry or defacing walls (67.1%) and "contamination of food (15.3%)", suggesting that chironomid midges influenced the daily life of the residents. 3. The selected causes of massive flights of chironomid midges were "pollution in Lake Suwa" and "decreases in the numbers of birds and dragonflies" as well as others. This means that the deterioration of the environmental situation around the lake may cause the "nuisance" of chironomid midges. 4. The respondents were more strongly interested in counterplans for the control of the chironomid midges made by administrative authorities than in plans made by each family. 5. "The distance from the lake shore" was the major factor contributing to the impression of chironomid damage. "The occupation of the respondent" was the second important factor. To redirect the insect flights away from the residential area, and to decrease the number of adult midges coming from the lake, are thought to be the most important measures for the resolution of this problem. PMID- 1890775 TI - [Studies on the massive flights of chironomid midges (Diptera: Chironomidae) as nuisance insects and plans for their control in the Lake Suwa area, central Japan. 3. Some experimental trials for control of nuisance midges and proposed counterplans]. AB - In the present paper the author tried to forecast the massive emergence of adult Tokunagayusurika akamusi midges from Lake Suwa. Furthermore, several control measures for chironomids were examined. The results obtained are as follows: 1. The forecast for the emergence of adult midges from the lake. A survey of the chironomid larva population was carried out at three stations in the lake. T. akamusi emerged at about the tenth day after the decrease of the larval number and at this time the temperature of the bottom water was within the range of 11 18 degrees C. The flights of adult midges were closely related to environmental factors such as air temperature, the strength and the direction of the wind and the light conditions. 2. The attraction of adult midges to lamps of various colors and wattages was studied. A comparative study on various colors of lights of the same intensity (100 W) showed that white was more attractive to chironomids than yellow, and that both colors were preferred to red, green, or blue. The experiment on light intensity showed that 100 W was more effective than 40 W and 20 W and that no differences in preference were observed between 100 W and 60 W white lamps. Therefore, the light intensity was thought to be more important than color for the control of adult midges. 3. Cyprinus is the natural enemy of the larva and pupae of T. akamusi. The total numbers of adult T. akamusi emerging from Enclosure A (in which there were 10 times as many Cyprinus as in the natural lake water), Enclosure B (no predator was present), and Station C (the natural lake) were 458, 1108, and 684 ind./m2, respectively. It was estimated that 38% of larvae or pupae were eaten by the fish in the lake, and by putting Cyprinus into the water, the percentage increased to 58%. It seems that Cyprinus has a significant effect in reducing the number of midges in field trials. 4. The control of T. akamusi may also be achieved by employing general prevention, by physical and biological means, depending upon the nature of the breeding source, and the cooperation of inhabitants and persons concerned is necessary to carry out the control of adult midges. 5. The proposals for the control of the nuisance caused by chironomid midges are as follows: (1) To make the inhabitants aware of the ecological role of chironomids in the lake, and the importance of protection of the natural ecosystem.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1890776 TI - [Recognition of stress in workers (report 1)--relationship between recognitions of causes of stress and stress reaction]. AB - Three aspects of the recognition of stress in 665 workers were investigated; namely, causes of stress, stress reactions and modifying factors. We examined the relationship among these aspects, in order to determine some different types of recognition. Several characteristics of the different recognition groups were also examined. 1) The workers who recognized that the causes of their stress were mainly "daily hassles" or "minor events which happened occasionally" accounted for 82.5% of all subjects, and the workers who recognized that their stress was caused mainly by "major life events" accounted for the remaining 17.5%. 2) The subjective stress of the workers in the "major life events" group was significantly larger than that of the workers in "daily hassles". 3) The group with stress due to "daily hassles or minor events" recognized the stress reaction mainly as "irritability", and their actual stressor was "busyness in work". In contrast, the recognition of a stress reaction due to a "major life event" group was represented by "depression/anxiety", and their actual stressors were not only major events such as "promotion or transfer" but also psychological factors such as "low emotional support of family members". 4) The mean age and rank of the "major life event" group were significantly higher than those of the other group. PMID- 1890777 TI - The effects of drinking, smoking and physical constitution on high density lipoprotein cholesterol, apolipoprotein AI and AII levels. PMID- 1890778 TI - [Compression of body by clothing--increase in urinary norepinephrine excretion caused by foundation garments]. AB - The urinary excretions of norepinephrine (NE) and epinephrine (EP) were measured to investigate the physiological effects of girdles worn by women to look attractive. 1) The urinary excretion of NE was remarkably increased by the wearing of a girdle in all the subjects examined, whether living conditions and stimulations were changed or remained unchanged. 2) The urinary excretion of NE was increased by wearing a girdle, regardless of the type of girdle or its intensity of compression. 3) The urinary excretion of NE tended to increase more by the wearing of a bodysuit having a large area of body compression than by the wearing of a girdle having a narrow area of compression. 4) The urinary excretion of NE showed no specific pattern of change, even when the subjects were accustomed to the use of a girdle. These findings may indicate that a girdle of even the best-fitting size exerts a kind of stress on the human body. PMID- 1890779 TI - [A study on health examination services under the Health Service Law for the Aged -multiple logistic regression analysis of service methods and the service acceptance rate]. AB - A survey on health services provided in accordance with the Health Service Law for the Aged was conducted in 3,278 cities, wards, towns, and villages throughout Japan in May 1985. Responses were returned from 2,645 districts and data on beneficiaries of these health services in 2,625 districts became available. Because the exact number of people constituting the subjects of health services could not be obtained, the service-acceptance rate was calculated by the number of people utilizing the services divided by the those in the population who were at least 40 years old. The service-acceptance rate was affected by both the size of the population of the local community and the methods of implementation of health services. Therefore, the mutual effects of population size and service methods were corrected by logistic regression analysis to find the relationship between methods of implementing health services and the response rate of the public in accepting the services. The service-acceptance rate was divided into two categories: one less than 30% and the other 30% and over. Odds ratios were calculated for an acceptance ratio of 30% and over. The results were summarized as follows: 1. In the jurisdictions where the local organizations cooperated in notifying citizens about the results of their general health examination, in comparison with the areas where there was no cooperation, the odds ratio was found to be 2.40. A similar comparison was made between the communities with local cooperation for notification of a general health examination and those communities without it. The odds ratio for the former was found to be 1.66.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1890780 TI - [Changes of procoagulant and fibrinolytic activities in the alveoli of rats exposed to ozone]. AB - The purpose of this study was to evaluate the role of ozone, a reactive product of environmental photochemical oxidation, in the development of pulmonary fibrosis. Male Wistar rats were exposed continuously to 0.5 ppm ozone for 1,4,7 and 14 days, and alveolar macrophages and lavage fluid obtained by bronchoalveolar lavage were examined. The results were as follows: 1) The total protein content in the lavage fluid was significantly increased compared to the control at 1 to 7 days by ozone exposure. Both alveolar macrophage and neutrophil counts increased in response to ozone exposure. However, approximately 90% of the free cells recovered were alveolar macrophages throughout the exposure period. 2) The plasminogen activator (PA) activity released from alveolar macrophages did not change in the group exposed for 1 day. But the activities were significantly high in the groups exposed for 4 to 14 days. 3) The PA activity of the lavage fluid showed a marked increase on the 1st day of ozone exposure, and subsequently decreased rapidly. However, the significantly increased activity was maintained throughout the exposure period. 4) In contrast, the procoagulant (PC) activity was unchanged on the 1st day of ozone exposure but the activity increased significantly on the 4th day, and was maintained at a high level until the 14th day. 5) The elastase inhibitory capacity (EIC) of the lavage fluid was significantly increased compared to the control by ozone exposure, but this difference was not seen throughout the exposure period when the EIC was corrected for the total protein content in the lavage fluid. These results revealed that both PA and PC activities increased in the alveolar fluid of rats exposed to 0.5 ppm ozone. The transition in the respective activities suggested that the fibrinolytic pathway in the alveoli was enhanced early in the exposure to ozone, while the coagulation pathway was enhanced later. This imbalance in coagulation homeostasis may be important in the regulation of fibrotic responses in the lungs of rats exposed to ozone. These findings are in agreement with morphological reports indicating that ozone exposure initially damaged the alveoli and later caused pulmonary fibrosis. PMID- 1890781 TI - [Representation and language development of profoundly mentally retarded children]. AB - The relationship between cognitive and language developments of ten profoundly mentally retarded children was examined through a longitudinal study. Cognitive processing tasks with matching-to-sample procedure were employed to examine the perceptual identification and representative function of objects. Concerning the development of language, both periods in which the comprehension and the utterance of object names emerged in each subject were recorded. There was no one to-one correspondence between the onsets of representative function and language development, i.e. the comprehension of object names emerged not only before, but also a long time after, the onset of representative function. Also, there was little possibility that the utterance of object names emerged simultaneously at the onset of representation. PMID- 1890782 TI - [Determinants of preferences among tasks with diagnosis of his/her own ability: individual and sex differences in self-assessment motivation and self-enhancement motivation]. AB - There are two different views on gathering information about self. According to "self-assessment" view, individuals choose tasks that are diagnostic about themselves, regardless of self-esteem implications. On the other hand, according to "self-enhancement" view, individuals choose tasks that are diagnostic only when they have positive self-esteem implications. Present research tested these predictions in Japanese college students, using for tasks with high or low diagnosticity of success and failure. In subjects with low uncertainty of self esteem, task preference increased with diagnosticity of success and diagnosticity of failure. This was consistent with self-assessment view. However, in subjects with high uncertainty of self-esteem, task preference didn't increase with diagnosticity of failure. In subjects with high self-esteem, task preference is high with high diagnosticity of failure than that of subjects with low self esteem. The results suggest large individual differences in gathering information about self. They also suggest that not only self-esteem but also uncertainty of self-esteem should be considered in studies of self-enhancement motivation. PMID- 1890783 TI - [A study of relation between phrasing and intertrial interval in reinforcement pattern learning in rats]. AB - Effects of the temporal interval on reinforcement pattern learning were investigated in four experiments using a runway. The reinforced trial was always the first trial for R5N sequence (Experiments 1a and 1b), and the fourth trial for 3NR2N sequence (Experiments 2a and 2b). Group S-ITI received the given sequence at 30-s ITI, Group L-INT received the same procedure as Group S-ITI except for a 30-min ITI inserted between Trials 3 and 4 (Experiments 1a and 2a). Group L-ITI received at 30-min ITI, Group S-INT did as Group L-ITI except for the ITI between Trials 3 and 4 was 30 seconds (Experiments 1b and 2b). It was found that the running speed on each of Trials 1 and 4 was faster than any other trials under R5N and 3NR2N sequences for Group L-INT. That is, the running pattern for Trials 1-3 was similar to that for Trials 4-6. On the other hand, the running speed on Trial 4 under R5N sequence and that on Trial 1 under 3NR2N sequence did not increase for Group S-INT. These results suggest that a longer or shorter ITI plays the roles of both phrasing cue and discriminative stimulus. For Group S-ITI and Group L-ITI, there was little evidence that sequences were phrased. Therefore, when trials are separated by equal ITIs, neither 30-s ITI nor 30-min ITI becomes a phrasing cue. PMID- 1890784 TI - [The effects of teacher stimulation on student learning motivation]. AB - The purpose of this study was to compare the effects of two types of teacher stimulation on 1) learning motivation of students who were poor in mathematics and 2) the students' impression of the teachers. One type of teacher stimulation was the encouragement of students who were poor in mathematics to make more effort because they had good ability but their ability was not yet realized. The other type of teacher stimulation was the encouragement of the students to exert themselves because of their previous lack of effort. A questionnaire, including the scenario describing the two types of teacher stimulation and several questions about the students' motivation and impression of the teachers, was administered to 378 elementary school, junior high school, and college students. The former type of teacher stimulation was partially more effective in the motivation of students and also fully more effective in the students' impression of the teachers than the latter type of teacher stimulation. PMID- 1890785 TI - [The interactive effects of comparative advertising on brand and company image change]. AB - The purpose of the present study was: 1) to investigate the effects of two types of comparative advertising--Merit-type (emphasizing positive aspects of their own brand) and Demerit-type (pointing out negative aspects of the rival brand); and 2) to find an effective strategy against comparative advertising of a rival company. Subjects were shown advertisements, and were then asked to evaluate those advertisements (17 items), the brands and company images (3 items) for these two companies. The results are as follows: Comparative advertising, especially of the Demerit-type, was the most conspicuous type of advertising, which also had a significant negative effect on the perception of rival brands. However, this type of advertising also had a negative effect on his own advertising, the brands advertised, and the company itself. Furthermore, it was found that when a rival company uses Demerit-type advertising, it is better not to respond by the same type, but to respond by Merit-type advertising. In such a situation, positive image of his own brand and company become significantly higher. PMID- 1890787 TI - [Effects of self-control strategies on 4-year-olds' resistance to temptation]. AB - Two experiments were conducted to examine the hypothesis that 4-year-olds' failure to resist to temptation was caused by their attention to motivational qualities of tempting objects. The forbidden toy situation forbidden to play with the attractive toy was used. In Experiment I that manipulated attention style of tempting objects, four conditions were set. Two conditions of these were conditions that prevented from attending to the motivational qualities of tempting objects and consisted of distraction condition that distracted from toy and toy-negative condition that evaluated the toy negatively. The other two conditions were control condition and toy-positive condition that attended to the motivational qualities of toy. The main results indicated that the transgression latencies of distraction and toy-negative conditions were longer than the other two conditions. In Experiment II, subjects were instructed to choose the strategy that they would use between stimulus pairs obtained by combining three strategy used in Experiment I. The results indicated that the number of subjects choosing toy-positive strategy were more than the other strategies in pairing toy-positive strategy with other two strategies. The hypothesis was supported from the present study. PMID- 1890788 TI - [The influence of multiple modeling and self-esteem on children's self reinforcement]. AB - The purpose of this study was to test the hypothesis that high (low) self-esteem children modeled after a lower (higher) SR criterion model in a multiple condition. Based on their self-esteem rating scores 48 third-graders were selected and divided randomly into two modeling conditions: a HL condition in which subjects viewed a video showing both an H model (high SR criterion) and an L model (low SR criterion), and an M condition that showed children only an M model (middle SR criterion). Both groups contained high and low self-esteem children. The number of tokens taken as self-reward in a task which was the same as that shown on the video was analysed. The following were the main results. The high self-esteem group in the HL condition took more tokens for their high score than the high one in the M condition. But the low self-esteem group in the HL condition tended to take fewer tokens for their high score than the low one in the M condition. In the HL condition, the low self-esteem group took fewer tokens than the high one. These results supported the hypothesis. PMID- 1890786 TI - [Analyses of preschool children's task choices based on the objective and subjective task difficulty levels]. AB - In this experiment, younger (4-year-olds) and older (6-year-olds) preschool children's task choices were analyzed based on the objective and subjective task difficulty levels. First, preschool children's understanding of the objective task difficulty levels was examined. While most older children understood the objective task difficulty levels, younger children did not. No understandable children's subjective task difficulty levels were checked. Next, younger and older children's task choices were analyzed respectively based on the objective task difficulty levels. As a result, there was no difference between an easy task choice and a moderate or a difficult task choice in both of them. Then, understandable children's task choices were reanalyzed based on the objective task difficulty levels and no understandable children's task choices were reanalyzed based on their subjective task difficulty levels. As a result, younger children chose an easy task more than a moderate or a difficult task. On the other hand, older children chose a moderate or a difficult task more than an easy one. PMID- 1890789 TI - [Response occurrence to the non-reinforced alternative through punishment in rats]. AB - Each of eight rats was located in the experimental chamber mounted with two levers. Lever-pressing to either of the two was maintained by a schedule of food. After that, a punishment schedule of electric shocks was added. Neither the reinforcement nor the punishment schedule was programmed on the other lever, i.e. the non-reinforced alternative. The effect of reinforcement, and the joint effect of reinforcement and punishment on responses to the non-reinforced alternative were compared. During punishment sessions, responses to the non-reinforced alternative occurred significantly more often than during reinforcement sessions. The number of responses to the non-reinforced alternative was negatively correlated with that to the reinforced alternative during punishment sessions. Nevertheless, the occurrence of responses to the non-reinforced alternative was mainly observed during the first few sessions in punishment schedule, or after stepping up the intensity of electric shock. These results were discussed in relation to the two theories and models of punishment. The results imply that the two theories and models of punishment are necessary to explain the effect of punishment. PMID- 1890790 TI - [Interaction between interleukin-1 and tumor necrosis factor productions by peripheral blood monocytes and nutritional disturbance in active pulmonary tuberculosis]. AB - Malnutrition is frequently observed in patients with pulmonary tuberculosis. We have already reported the nutritional disturbance in those patients by comprehensive nutritional assessment. But the mechanism of this nutritional disturbance remains unclear. We anticipated that cytokines contributed to the nutritional disturbance. To elucidate this mechanism we measured the productions of interleukin-1 (IL-1) and tumor necrosis factor (TNF) by peripheral blood monocytes, and correlated them with nutritional parameters in those patients. These cytokines had been reported to mediate metabolic alterations in inflammatory process. Subjects were 45 patients with bacteriologically confirmed pulmonary tuberculosis and their controls matched by age and sex. Adherent monocyte at 0.5 x 10(6)/ml were stimulated by lipopolysaccharide (LPS), and the culture supernatant was measured by ELISA for IL-1 and TNF. In order to assess nutritional status we measured serum albumin, transferrin, prealbumin, retinol binding protein, branched chain amino acid (BCAA)/aromatic amino acid (AAA) ratio as amino acid imbalance index, % ideal body weight (%IBW), % arm muscle circumference (% AMC) as muscle mass index, % triceps skin fold thickness (% TSF), as fat store index. The results were as follows: (1) Patients with active pulmonary tuberculosis were confirmed to be malnourished in visceral proteins, plasma amino acid, and anthropometric indices. (2) In patients with moderate or mild nutritional depletion the production of IL-1 and TNF was higher than that in healthy controls, and significantly correlated inversely with the nutritional parameters. (3) In patients with severe nutritional depletion the production of IL-1 and TNF was lower than that in healthy controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1890791 TI - [In vitro susceptibilities of Mycobacterium avium and Mycobacterium intracellulare to various drugs]. AB - Mycobacterium avium and M. intracellulare isolated from patients infected with M. avium complex (MAC), which were identified by Gen-Probe Rapid Diagnostic System for the MAC, were studied for susceptibility to various antimicrobial agents, including rifampicin, rifabutin, kanamycin, streptomycin, amikacin, ethambutol, clofazimine, isoniazid, ofloxacin, ciprofloxacin and cycloserine. Ratio of resistant strains to test strains to a given agent at prescribed concentration in cases of M. avium and M. intracellulare was compared with each other. Test strains of M. avium were more resistant to rifampicin, rifabutin, kanamycin, streptomycin, amikacin, ethambutol and clofazimine than test strains of M. intracellulare. Conversely, the M. avium strains were more susceptible to ofloxacin, ciprofloxacin and cycloserine than M. intracellulare strains. The difference in the drug susceptibility between M. avium and M. intracellulare was statistically significant by chi 2-test (P less than 0.005-0.05). There was no statistically significant difference between the two MAC species with respect to the susceptibility to isoniazid. PMID- 1890792 TI - [A case of apyretic miliary tuberculosis which was discovered accidentally]. AB - A 78 year-old female was referred to our hospital, because diffuse miliary shadows in bilateral lung fields were discovered during upper G.I. series. She did not complain of fever or display any chest symptoms. Her laboratory data on admission revealed mild hypoxemia and high serum CA 19-9. The transbronchial lung biopsy specimen proved epithelioid cell granulomas. M. tuberculosis was observed on culture from the sputa, urine and bronchoalveolar lavage fluid. She was diagnosed to have miliary tuberculosis, and antituberculous drugs were administered. After the antituberculous therapy, the diffuse miliary shadows on the chest X-ray diminished gradually, and the laboratory data improved. No elevation in the body temperature was seen during the entire clinical course. Though it is known that miliary tuberculosis in elderly patients is often atypical and has mild symptoms, miliary tuberculosis without fever is very rare. PMID- 1890793 TI - [The comparison of drug susceptibility of antituberculous agents against colonizing M. intracellulare and infectious M. intracellulare]. AB - The susceptibility of antituberculous agents against colonized M. intracellulare which were isolated from patients with pulmonary disease and infectious M. intracellulare (pathogens) isolated from atypical mycobacterial culture was investigated. Aminoglycosides were more potent against colonized organisms than against pathogens. Isoniazid, ethambutol and rifampicin showed less potent antimicrobial activity against both colonized organism and pathogens as compared to aminoglycosides. On the contrary susceptibility of cycloserine against colonized organisms was as potent as against pathogens. PMID- 1890794 TI - Transport mechanisms in kidney proximal tubule examined using chloride-sensitive fluorescent indicators. PMID- 1890795 TI - Transcellular chloride transport in the proximal tubules: mechanisms and physiological significance. PMID- 1890796 TI - Intracellular pH regulation in epithelial cells. PMID- 1890798 TI - Illumination, wavelength selection, and detection in fluorescence microscopy. AB - The presently available devices for the illumination, changing of wavelengths, and detection of the resultant fluorescence of biological samples viewed in the light microscope have been described and compared. The optimal choice for illumination is a xenon arc lamp with a filter wheel wavelength selector. The optimal choice for an imaging detector is an intensified CCD (charge-coupled device) camera. These combinations produce the most rapid, stable, and reproducible results when fluorescence measurements are made on living epithelial cells or isolated renal tubules. Techniques for the simultaneous acquisition of fluorescence and differential interference contrast (DIC) images have also been described and compared. PMID- 1890797 TI - Cellular mechanisms of Cl- transport in outer medullary collecting duct. AB - The OMCDi secretes Cl- when perfused and bathed with symmetrical solutions. The route for this transepithelial Cl- movement appears to be the paracellular pathway, and the driving force is the lumen positive voltage generated by the process of electrogenic H+ secretion. Currently, there is no evidence to support the existence of a significant transcellular route for transepithelial Cl- movement. Although the primary function of the OMCDi is related to urine acidification, Cl- plays an important role in this process. The basolateral membrane of the OMCDi cell contains a band-3 related Cl-/HCO3- antiporter and a Cl- conductance. The Cl-/HCO3- antiporter serves as the primary route for the efflux of HCO3- generated during the process of H+ secretion. The Cl- conductance allows Cl- brought into the cell by the antiporter to recycle across this membrane. This conductance also serves to maintain cell charge balance. Accordingly, for each equivalent of H+ leaving the cell across the apical membrane, a Cl- equivalent exits the cell across the basolateral membrane. Based on whole-cell patch-clamp studies, this Cl- conductance is blocked by the Cl- channel blocker DPC. This conductance may also have a finite permeability to HCO3 , and thus could serve as a secondary route for cellular HCO3- efflux. Lastly, the conductance is activated by the beta-adrenergic agonist isoproterenol. PMID- 1890799 TI - Role of the loop of Henle in urinary acidification. PMID- 1890800 TI - Regulation of bicarbonate and ammonium absorption in the thick ascending limb of the rat. PMID- 1890801 TI - Cortical collecting duct bicarbonate secretion. PMID- 1890802 TI - Morphological adaptation of the collecting duct to acid-base disturbances. PMID- 1890803 TI - Role of Ca2+/H+ antiporter in the kidney. AB - Three different mechanisms for H+ transport mediated by Ca2+ have been reported. First is an ATP-dependent Ca2+/H+ antiporter which is catalyzed by (Ca2+ + Mg2+) ATPase in plasma membrane. Second is a compensatory Ca2+ movement associated with an ATP-dependent H+ pump catalyzed by H(+)-ATPase in endosome. Third is a mitochondrial Ca2+ movement driven by an electrophoretic H+ driving force. All these processes must play a critical role on transfering messages between Ca2+ and H+. Data indicate that an ATP-dependent Ca2+ pump is an electroneutral Ca2+/H+ antiporter in renal tubular cells as well as in other nonrenal cells. The existence of this process is compatible with the physiological phenomena of Ca2+ and H+ transport in renal tubules, although we still lack direct evidence to comprehend the role of the Ca2+/H+ pump in the kidney. PMID- 1890804 TI - NH4+ transport in the kidney. AB - We have described the overall process that is responsible for the efficient transfer of ammonium from its production site in the proximal tubule cells to the final urine. The mechanism depends on direct NH4+ transport at a number of sites. There appears to be a predominance of NH3 over NH4+ transport in net total ammonia transport only in the collecting ducts and possibly the descending limbs of Henle's loop. Several examples of physiologically important direct NH4+ transport in the kidney were described. First, coupled Na/NH4/2Cl transport across the apical membrane of the thick ascending limb of Henle's loop mediates secondary active transport of ammonium, which drives countercurrent multiplication of ammonium in the renal medulla. Second, part of the NH4+ uptake across the apical membrane of the thick ascending limb may occur as a result of penetration by NH4+ through apical K+ channels. It is unknown whether NH4+ penetrates K+ channels in other tubule segments. Third, NH4+ can be actively transported into cells by substitution of NH4+ for K+ on the Na-K-ATPase. This NH4+ transport process is likely to be rapid enough to be physiologically significant only in the inner medulla, where NH4+ concentrations are high enough to successfully compete with K+. Fourth, NH4+ penetrates the paracellular pathway in some nephron segments such as the proximal tubule and thick ascending limb. Simple passive diffusion of NH4+ via the paracellular pathway is thought to be physiologically important in the thick ascending limb where it contributes to net NH4+ absorption. PMID- 1890805 TI - Significance of in vivo detection of tumor necrosis factor. PMID- 1890806 TI - Regulatory pathways in tumor growth and invasion. AB - Human tumor cells constitutively produce a variety of growth factors, cytokines, chemoattractants, motility factors, and proteolytic enzymes and their inhibitors. Juxtaposed normal cells such as fibroblasts, endothelial cells, and monocytes are also potential producers of most of these factors but, in general, they require specific signals to trigger synthesis and/or to release biologically active factors. Growth stimulation of normal and malignant cells, angiogenesis, and stroma formation within malignant lesions, tissue degradation by invasive tumor cells, cell motility, detachment of tumor cells from lesions and/or attachment to basement membranes involve complex interactions between autocrine, paracrine, and endocrine factors. Despite the complexity of such interactions, preliminary regulatory pathways can now be proposed that may help to explain the role for both positive and negative regulators in tumor development, growth, and invasion. PMID- 1890807 TI - Tumor necrosis factor production by glomerular macrophages in anti-glomerular basement membrane glomerulonephritis in rabbits. AB - The production of tumor necrosis factor (TNF) by nephritic glomeruli and glomerular macrophages was studied in antiglomerular basement membrane antibody induced glomerulonephritis (anti-GBM GN) in rabbits. Autologous phase injury was associated with glomerular macrophage infiltration and augmented TNF production by isolated nephritic glomeruli (day 8, 1.15 +/- 0.10 ng/10(3) glomeruli/24 hours; normal, 0.01 +/- 0.01 ng/10(3) glomeruli/24 hours; p less than 0.05). In contrast, during the heterologous phase, in which macrophages were not prominent, injury was not associated with augmented glomerular TNF production. Glomerular TNF bioactivity had a molecular weight and isoelectric point consistent with rabbit TNF and was inhibitable by an anti-TNF antibody. TNF was also identified in nephritic glomerular supernatants by Western blotting. Macrophages isolated from glomeruli of rabbits developing autologous phase anti-GBM GN produced significantly more TNF (0.14 +/- 0.02 ng/10(3) macrophages/24 hours) than blood monocytes (0.03 +/- 0.02 ng/10(3) monocytes/24 hours, p less than 0.05) from the same rabbits. Macrophage depletion of rabbits with autologous phase anti-GBM GN significantly reduced proteinuria, prevented glomerular macrophage accumulation, and blocked augmentation of glomerular TNF production. These studies demonstrate the association of glomerular TNF production with the development of glomerular macrophage infiltration and injury in anti-GBM GN and suggest that infiltrating glomerular macrophages are the major source of glomerular TNF. PMID- 1890809 TI - Production and characterization of a monoclonal antibody against human glomerular heparan sulfate. AB - After immunization with heparan sulfate proteoglycan (HSPG) isolated from human glomeruli, two mouse monoclonal antibodies (mAbs) against heparan sulfate (HS) were obtained. Both mAbs were of the IgM isotype and showed identical specificity. One of these, mAb JM-13 is described in detail. In enzyme-linked immunosorbent assay and Western blotting, reactivity was found with human glomerular basement membrane HSPG and HS. No binding occurred to the core protein of HSPG obtained after removal of HS with trifluoromethanesulfonic acid. In enzyme-linked immunosorbent assay, mAb JM-13 did neither bind to other proteoglycans, nor to other basement membrane components like collagen type IV, laminin, or fibronectin. In indirect immunofluorescence on cryostat sections of human kidneys, a restricted staining of tubular basement membranes was observed along with staining of the vascular basement membranes. In the glomerulus, a weak, fine granular staining was seen along the capillary wall and in the mesangium. MAb JM-13 bound also to the basolateral cell membranes of proximal tubular cells, to the cell membranes of cultured human and rat glomerular visceral epithelial cells, rat mesangial cells, human hepatocytes in culture, and in liver cryostat sections, indicating also a recognition of cell surface associated HS. Pretreatment of the sections with heparitinase abolished binding of JM-13, whereas treatment with chondroitinase ABC had no effect. Inhibition studies in enzyme-linked immunosorbent assay as well as in indirect immunofluorescence corroborated the HS specificity of mAb JM-13. In conclusion, mAb JM-13 binds to an epitope on the HS chains of glomerular, tubular, and cell surface-associated HSPG. PMID- 1890808 TI - Effect of simian immunodeficiency virus infection on tumor necrosis factor-alpha production by alveolar macrophages. AB - We studied the release of tumor necrosis factor-alpha (TNF alpha), a vital immunoregulatory cytokine, by alveolar macrophages (M phi s) infected with simian immunodeficiency virus (SIV) in vitro or collected from SIV-infected macaques. For in vitro studies, M phi s were harvested by bronchoalveolar lavage from 5 normal animals and infected in flasks with SIV (10(4)TCID50/2.5 x 10(6) M phi s). After 7 to 10 days, cytopathic effect was prominent and 68 +/- 2% of M phi s were immunoreactive for p27 core protein. Uninfected (control) and SIV-infected M phi s were then cultured for 24 hours in 96-well plates (10(5) M phi s/well) while challenged with lipopolysaccharide (LPS; 100 micrograms/ml). TNF alpha was assayed in culture supernatants by an enzyme-linked immunosorbent assay (detection limit, 50 pg/ml) and results were expressed as pg TNF alpha/ml/10(3) M phi s (mean +/- SEM). TNF alpha was not detected in unstimulated wells. TNF alpha release by control and SIV-infected M phi s was similar (6.6 +/- 0.7 and 7.9 +/- 1.1 pg/ml/10(3) M phi s, respectively). We also studied TNF alpha release by alveolar M phi s from 8 animals infected with SIV (3 asymptomatic, 5 with acquired immune deficiency syndrome virus (AIDS]. One animal with AIDS had p27+ M phi s. Alveolar M phi s from asymptomatic animals released significantly more TNF alpha (10.3 +/- 1.1 pg/ml/10(3) M phi s) than did animals with AIDS or uninfected macaques (5.2 +/- 0.8 and 7.0 +/- 0.6 pg/ml/10(3) M phi s, respectively) (p less than 0.01). However, M phi s from monkeys with AIDS failed to respond to LPS after 7 to 10 days in culture. In summary, in vitro infection with SIV does not cause constitutive TNF alpha release or alter the response of cultured M phi s to LPS. When kept in culture, M phi s collected from asymptomatic, SIV-infected animals retain their response to LPS, whereas M phi s from animals with AIDS lose the capacity to produce TNF alpha. Furthermore, M phi s cytokine production is exaggerated before overt clinical disease, but not as a direct result of infection with SIV. PMID- 1890810 TI - Calcium and acidosis in renal hypoxia. AB - The effects of lowering extracellular calcium concentration on hypoxic injury in the thick ascending limb of Henle (TAL) were studied in the isolated perfused rat kidney. At standard conditions of pH 7.4 and total perfusate calcium 1.9 mM, widespread TAL necrosis results from the combined effects of low medullary O2 delivery and the demands of solute transport activity. Reducing calcium to 0.5 or 0.1 mM, effectively prevented TAL membrane fragmentation. This cytoprotection was not accompanied by improved O2 delivery or by any consistent effects on renal physiology (glomerular filtration rate, sodium reabsorption, free water clearance or O2 consumption) that might have suggested that the mechanism was reduced O2 demand. In addition, the medullary ATP depletion which characteristically precedes TAL necrosis was not reversed. Finally, reduced perfusate calcium also markedly decreased TAL damage in an alternative model of hypoxia-like injury caused by a respiratory uncoupler. In aggregate, these findings indicate that reducing extracellular calcium does not prevent hypoxia itself, but rather disrupts the mechanism of its effects on cell integrity. The relationship of H+ and Ca2+ in the pathogenesis of hypoxic TAL injury was also studied. Lowering media pH to 7.0 reduced TAL damage but this cytoprotection was overcome by increasing media calcium concentration. Furthermore, with more severe acidosis (media pH 6.5 or 6.0), progressively greater perfusate calcium concentrations were required to reproduce severe TAL damage. These results indicate that extracellular calcium promotes the development of hypoxic TAL necrosis and that the cytoprotective effect of acidosis in hypoxia may be to counteract the calcium dependent mechanism of injury. PMID- 1890811 TI - Detection of a monocyte/macrophage differentiation antigen in routinely processed paraffin-embedded tissues by monoclonal antibody Ki-M1P. AB - A new monoclonal antibody Ki-M1P that is raised against supernatants of detergent solubilized human lymph node tissue is described. Ki-M1P recognizes in particular monocytes and their macrophage derivatives as tested by light- and electron microscopic immunohistochemistry. Granulocytes, dendritic cells as the accessory cells of humoral and cellular immune response, and epithelial, endothelial, neural, and mesenchymal cells do not react with Ki-M1P. In extensive application Ki-M1P has proven to be a useful marker for distinguishing monocytic leukemias within FAB groups M4 and M5. The recognized antigen is composed of five proteins with molecular masses of about 60, 92, 98, 124, and 150 kDa in blood monocytes, whereas tissue macrophages tested so far expressed only the 60-kDa protein. Because the Ki-M1P antigen is not destroyed or masked during routine fixation and paraffin embedding of biopsy tissue samples, Ki-M1P represents a useful diagnostic reagent for the identification of physiological functional and pathologic reaction forms as well as neoplastic variants of the human monocyte/macrophage system even in retrospective studies. PMID- 1890812 TI - Temporal and spatial patterns of proto-oncogene expression at early stages of toxic liver injury in the rat. AB - Sequential and transient expression of c-fos, c-jun, c-myc, c-Ha-ras and c-Ki-ras proto-oncogene RNA transcripts with zonal heterogeneity was demonstrated in virtually all hepatocytes of adult rat liver by in situ hybridization with single stranded, [35S]-labeled cRNA probes at various time points after intraperitoneal administration of a single dose of carbon tetrachloride (CCl4). After a brief interval, elevated RNA levels of these genes were also observed in nonparenchymal cells. A second phase of proto-oncogene expression was characterized by high RNA levels in only a fraction of parenchymal cells with preference of mediolobular areas. Distribution and number of these cells were comparable tl hepatocytes expressing the proliferation-associated nuclear antigen Ki-67 72 hours after toxic injury. Oncogene expression in the nonparenchymal compartment correlated with distinct morphologic changes preceding type I procollagen gene expression by desmin-positive perisinusoidal cells, accumulating together with numerous c-fms expressing cells in the areas of hepatocellular necrosis. We conclude that zonal hepatic destruction by carbon tetrachloride induces proto-oncogene expression with distinct temporal and spatial patterns initiated by the most severely damaged hepatocytes. Proto-oncogene products thus represent valuable markers of cellular activation preceding and accompanying various aspects of tissue repair reactions. PMID- 1890813 TI - Distribution of the alpha 1-alpha 6 integrin subunits in human developing and term placenta. AB - The distribution of the alpha 1-alpha 6 as well as alpha v, beta 1, beta 3 and beta 4 integrin subunits in human first and second trimester and term placentas was studied by indirect immunofluorescence microscopy using a panel of monoclonal antibodies (mAbs). In first and second trimester villi, the alpha 1 and beta 1 integrin subunits were detected in the stromal cells, that were mostly also immunoreactive for desmin. Desmin-positive stromal cells were also found in villi of term placentas, but the stroma was negative for anti-alpha 1 and -beta 1. In the villous trophoblast, anti-alpha 6 and -beta 4 revealed a distinct basal immunoreactivity during all stages of development, whereas immunoreactivity for the alpha 3 and beta 1 subunits emerged during the second and third trimesters. Throughout placental development, endothelia of villous capillaries reacted prominently with anti-alpha 1 and -beta 1. Intermediate trophoblastic cells displayed a somewhat heterogenous immunoreactivity for the beta 1, alpha 1, alpha 3 and alpha 5 integrin subunits, and differed from villous trophoblast also in their lack of expression of the alpha 6 and beta 4 subunits. While nondecidualized endometrial cells displayed weak reactivity for the alpha 1 and beta 1 integrin subunits, the individual decidual cells presented both a basement membrane and a cell surface-confined immunoreactivity for anti-alpha 1, -alpha 3, and -beta 1. The results suggest a role for integrins in placental development, and show that expression of integrins is modulated during the differentiation of trophoblast, villous stroma, and decidual cells. Furthermore, the basal localization of alpha 6 beta 4 and alpha 3 beta 1 integrins suggests that they are employed as basement membrane receptors in the villous trophoblast, and the emergence of the alpha 3 beta 1 complex may reflect that the cytotrophoblast and syncytiotrophoblast recognize the basement membrane differently. PMID- 1890814 TI - A novel intracellular pathway for rat intestinal digestive enzymes (alkaline phosphatase and sucrase) via a lamellar particle. AB - To identify the mechanism of intestinal alkaline phosphatase (IAP) release into serum that is known to be associated with fat feeding, both luminal and serum IAP as well as sucrase-isomaltase levels were monitored by rocket electroimmunoassays and by immunogold labeling electron microscopy. Luminal and serum IAP, and to a much lesser extent sucrase-isomaltase, peaked at 7 hours after fat feeding. Analysis of the luminal IAP by isoelectric focusing showed that the enzyme had a slightly different pI than brush border IAP, but was still partially membrane bound, whereas serum IAP was no longer membrane bound. In parallel, by morphology, IAP and sucrase-isomaltase localized to intra- and extracellular lamellar membranous particles, most conspicuous at 7 hours after fat feeding, while very scarce in nonfat-fed animals. The membranous particles bearing the enzymes were commonly associated with fat droplets. These data are consistent with the existence of a novel pathway, possibly secretory, for IAP and sucrase isomaltase via lamellar bodies, leading to appearance of the enzymes in lumen and serum, with subsequent release from the membrane extracellularly. They also offer an explanation for the known association of the increased secreted IAP after fat feeding. PMID- 1890815 TI - Neurogenic signals regulate chromaffin cell proliferation and mediate the mitogenic effect of reserpine in the adult rat adrenal medulla. AB - The adrenal medulla is innervated by nerve fibers from several sources, which synapse on chromaffin cells and stimulate the secretion of catecholamines. The antihypertensive agent reserpine is known to reflexively increase this neurogenic stimulation by depleting catecholamine stores, and long-term administration of reserpine is associated with adrenal medullary hyperplasia and neoplasia. To determine the role of neurogenic signals in regulating normal and reserpine stimulated proliferation of chromaffin cells, the incorporation of 5-bromo-2' deoxyuridine (BrdU) into replicating nuclei was assessed in the adrenal medulla of adult rats. Unilateral adrenal denervation caused a 4-5 fold decrease in chromaffin cell labeling by 5-bromo-2'-deoxyuridine during a 2-week labeling period. Denervation also prevented stimulation of labeling in animals receiving reserpine in their diet. These findings suggest that neurogenic control of cell proliferation may play an important role in the pathogenesis of adrenal medullary hyperplasia and neoplasia, and in the normal development of the peripheral and central nervous systems. PMID- 1890816 TI - Medicare update. PMID- 1890817 TI - Delta hepatitis: first case identified in South Carolina. AB - Reports now document hepatitis D infection in diverse clinical settings in the United States, indicating that the infection is becoming more common. The demonstration of the first case of Delta hepatitis in South Carolina emphasizes the need for a high index of suspicion for infection by this virus in the evaluation of patients with hepatitis. PMID- 1890818 TI - Management of facial fractures. PMID- 1890820 TI - HIV insurance available. PMID- 1890819 TI - Hyponatremia: dangers of treatment. AB - Hyponatremia is a common clinical diagnosis. Rapid correction may result in neurological deterioration due to myelinolysis in the central pons and extrapontine areas of the brain. Rapid correction may result in serious neurological sequela, including death and has no significant advantage. Slow correction of chronic hyponatremia appears to be the treatment of choice. PMID- 1890821 TI - Coherent average technique--a tutorial review. AB - This paper highlights the effects of digitization in relation to the effective numberical range over which the signal to be averaged has to be resolved. The effect of quantization noise on the number of averaging cycles is assessed and it is shown that for averaging weak signals such as the HIS bundle electrogram, high resolution analogue-to-digital (A/D) conversion is required so as to prevent a substantial increase in the number of averaging cycles. Also the requirement for adequate low-pass filtering is discussed and relationships between the numerical range of the A/D conversion process, the order of the low-pass filter, its cut off frequency and sampling frequency are formulated. PMID- 1890822 TI - An automatic matching technique for patient alignment. AB - An automatic system of patient alignment is required in order to monitor changes that occur in the period between magnetic resonance scans. For each scan of the patient a prime requisite is to register the images with respect to each other. The orthogonal relationship between the sagittal and transverse images should, in principle, identify a single common line at the intersection of the two image planes. The basis of the comparison requires spatial registration of the two images to correct for the probable translational and rotational tilts as well as for the geometrical and intensity distortions. This paper describes a number of automatic techniques which compare, pixel-by-pixel, first two synthetic images, and then their application to real images obtained separately from the same head and neck object field. The robustness, computational cost and effectiveness of the techniques presented are discussed, and computed results on real data for the most promising technique based on the Ratio Absolute Difference algorithm are presented. PMID- 1890823 TI - Value of coining on the improvement of endurance in slotted intramedullary nails. AB - Cracking of intramedullary nails, starting at the proximal end of the partial slot and propagating in a circumferential direction, has been observed. These partial cracks are relatively frequent, although full failures are very rare and do not disturb fracture healing. Coining is a cold-working process used to improve the endurance of structures with residual compressive stresses generated by plastic deformation. The influence of coining was investigated to evaluate its practical value in controlling these fatigue cracks. Bending and torsional tests were performed on high frequency machines. Coined zones of different shapes and depths were examined, comparing the elapsed number of load cycles with crack initiation. The results showed that the endurance of coined nails was improved by factors of approximately 10 and 5 in bending and torsion, respectively. This increase in fatigue life corresponds to a more than 50% larger dynamic load after a million cycles. Variations in coining shape and depth did not yield any significant differences. PMID- 1890824 TI - Determination of stress levels and profiles in the periodontal ligament by means of an improved three-dimensional finite element model for various types of orthodontic and natural force systems. AB - This study was undertaken to investigate the stress-strain levels and distribution within the periodontal ligament for various types of physiological and orthodontic force systems, assuming that the bone resorption process, leading to tooth movements, is partly controlled by those conditions. Two finite element models were developed, simulating a full and partial mandibular morphology, respectively. Both models were based on morphology and physical parameters of human autopsy material. The effect of changing material parameters and structure, type of boundary conditions, calculation method and fineness of the model on the stress levels and profiles in the periodontal ligament was evaluated by a series of tests. A structure optimization technique was used to investigate the load bearing characteristics of the mandible and the influence of the anisotropic material properties of both the mandible and the segment. A 'multiple modelling' technique based on both the mandible and the segment was developed to test various types of boundary conditions in the analysis of the segment. Results presented as 'stress profiles' showing the correlation between the applied force system and the stress distribution in the periodontal ligament, based on the improved finite element models, were established. PMID- 1890825 TI - Electrochemical method for direct measurement of oxygen concentration and diffusivity in the intervertebral disc: electrochemical characterization and tissue-sensor interactions. AB - A method was developed for the in vivo measurement of oxygen concentration and diffusivity in the intervertebral disc using a bare gold cathode. The effects of surface adsorption were quantified using electrochemical methods and it was demonstrated that valid data can be obtained despite interactions between the electrode and the macromolecules of the intervertebral disc. The technique is used to show the dependence of the oxygen transport properties on tissue water content. PMID- 1890826 TI - A beat-by-beat analysis of electrocardiograms from cardiac transplant recipients. AB - A software system is described for producing a beat-by-beat analysis of the electrocardiograms from patients after heart transplantation. Pacemaker spikes are automatically detected and eliminated from the signals. R waves are located by a robust and accurate two-step algorithm. Based on the variable length of single heart beats, the Fourier coefficients of three orthogonal surface leads and of two intracardiac leads are calculated beat-by-beat. Power spectra are then obtained by combining contributions from the variable fundamental frequency and its multiples (harmonics) into fixed frequency classes of 1 Hz width and averaging over 60-120 cardiac cycles. Additionally, averaged beat-by-beat power spectra are calculated for windowed QRS complexes and T waves. As by-products, single beat quantities, such as R-R and R-T intervals, averaged signals for all leads, and the orientational autocorrelation function of the electrical vector of the heart, are obtained. Following beat-by-beat evaluation, mean values and standard deviations are obtained for all quantities. PMID- 1890827 TI - Detection of internal fixation plate loosening by means of an analysis of vibratory responses. AB - This paper reports an in vitro investigation of a non-invasive method for detecting the loosening of internal fixation plates. The technique involves the electromechanical vibration of the fixation plate and the electromagnetic detection of its vibratory response. Frequency domain analysis of both fixed and loosened plates are compared and spectral artefacts are suggested as a means of classifying the mode and extent of plate loosening. An algorithm for the diagnosis of loose plates using the new approach is included. PMID- 1890828 TI - Fabrication and biocompatibility of a porous bioglass ceramic in a Na2O-CaO-SiO2 P2O5 system. AB - A porous bioglass ceramic was prepared from a finely pulverized bioglass powder mixed with particles of two sizes (5 and 500 microns) of 30% by weight with the foaming agent polyethylene glycol 4000 (HO (C2H4O) nH). The batch composition of the bioglass was Na2O 12%, CaO 28%, SiO2 50% and P2O5 10% by weight. The specimens, formed by pressing, were sintered in a high temperature furnace. In this study we are concerned with the preparation and microstructure of the material and its performance in biological tests. The microstructure and crystalline phases of the material were investigated by differential thermal analysis, X-ray diffraction analysis, transmission electron microscopy and scanning electron microscopy. In a biomedical examination, it was shown that the porous material was compatible with animal tissues. The microstructure of the implant indicated that newly grown bone interlocked well with the glass ceramic and that macropores and micropores were distributed uniformly in the material, which provided channels for bone ingrowth and improved the microscopic bioresorption. PMID- 1890829 TI - Simple model of circulatory system dynamics including heart valve mechanics. AB - This paper describes an extension of the Windkessel model of circulatory system dynamics, which takes into account the opening action of the mitral and aortic valves, including stenotic and regurgitant orifices. The starting point for the model is the ventricular emptying/filling curve which is taken from a quasi physiological ventricular flow relationship which incorporates variation of systolic and diastolic intervals with cycle rate. The valves are assumed to open with a linear rise in area up to maximum orifice, followed by a period at maximum orifice and then a linear fall-off in area to the closed position (which may allow regurgitation). Flow through the valves is assumed to be governed by the Gorlin equation. Peripheral resistance and compliance are considered as fixed parameters of the arterial system. The model is useful in helping to understand the complex interaction between valvular mechanics and the rest of the cardiovascular system. Applications of the model are illustrated by considering isolated aortic stenosis, isolated aortic regurgitation, cardiac adaptation in the presence of these two abnormalities and the effects of variation of peripheral resistance on pressures within the cardiovascular system. PMID- 1890830 TI - The physiological basis for a flexible condylar tibial plateau design. AB - Knee resurfacing is a successful treatment for osteo- and rheumatoid arthritis in elderly patients. The application of this treatment to younger more active and obese persons has the potential to produce premature wear, loosening, and undesirable bone remodelling. A new generation of more physiologically compatible components is required for these situations. This paper discusses the design and analysis of a prototype tibial base plate aimed at physiological load transfer. Incorporated in the design are mechanisms to alleviate lift-off phenomena, bone stress concentrations, stress shielding, and micromotion at the bone-implant interface. The design requires viable cancellous bone stock, so that the bone may respond by remodelling to the dynamic loading during normal ambulatory activities. PMID- 1890831 TI - Design of an automated temperature mapping system for ultrasound or microwave hyperthermia. AB - An automated temperature mapping system was designed to accomplish the following goals: remote control mapping; a maximum position error of 0.5 mm; mapping simultaneously on several channels; real-time screen display on a dedicated computer; to be inexpensive, and have a simple patient interface and set up. A four channel, microstepper system was fabricated for less than $1000 and controlled by an IBM-AT computer. The system utilizes direct drive of Luxtron fibre-optic probes fed through thin flexible Teflon tubing which allows for patient movement. The driving and control software were written in the programming language "C". Mapping parameters for each independent channel include start and stop positions and map increment. The software permits the user to automatically find the maximum temperature along a track in three passes of 2.0, 1.0 and 0.5 mm steps. The latter two passes take five or seven readings centred about the maximum of the previous pass. A high resolution monitor plots the temperatures in real time, overlaying the previous map in a new colour. A screen dump was written to drive a colour printer with the plot information. The computer evaluates each plot to safeguard against any shift in the maximum location. Visualization of orthogonal pullbacks provides rapid feedback and aids in the repositioning of superficial hyperthermia transducers. The time saved over the previous manual mapping methods easily justifies the additional set up time. PMID- 1890832 TI - Relationship between loading dose and infusion rate to achieve any fraction of the steady-state level in any compartment model. AB - When a drug is infused at a constant rate K0, the time necessary for the concentration to reach a satisfying threshold of effectiveness may be too long. To achieve this level faster, it is useful to give simultaneously a dose D, of the same drug by intravenous injection. This paper proposes the calculation, as a function of K0 and model parameters, of the loading dose D necessary to reach, in a time T, any fraction of the asymptotic value of the amount of drug in a compartment receiving a constant rate infusion, for any n-compartment model. As an example, the expression of D for mammillary and catenary pharmacokinetic models is derived. PMID- 1890834 TI - The risky shift. PMID- 1890833 TI - Detection of quartz in renal calculi to exhibit piezoelectricity. PMID- 1890835 TI - Complications of infection and immunologic status after surgery for patients with esophageal cancer. AB - Correlations between defective cell-mediated immunity (CMI) and infections following surgery for esophageal cancer were evaluated. Peripheral lymphocytes, T cells, B cells, PHA transformation, and PPD skin test were measured in 81 patients with esophageal cancer, 58 with gastric cancer, and 50 healthy controls. The depression of CMI was predominant to a similar extent in patients with esophageal cancer and in those with gastric cancer. The average level of PHA transformation immediately before surgery was significantly lower in the esophageal cancer patients with fatal septic complications than in those without such problems. Although preoperative radiation therapy markedly depressed the levels of the four parameters, this association was also noted in 28 patients not given radiation. It thus appears that PHA transformation may be valuable in the prediction of fatal septic complications after major surgery in patients with esophageal cancer. PMID- 1890836 TI - In vitro response of a human colon tumor xenograft and a lung adenocarcinoma cell line to alpha-difluoromethylornithine alone and in combination with 5 fluorouracil and doxorubicin. AB - We have investigated effects of alpha-difluoromethylornithine (DFMO), both as a single agent and in combination with 5-fluorouracil (5-FU) against a human colon tumor xenograft (T6) grown as primary tissue culture in serum-free medium and in combination with doxorubicin (DX) against a human lung adenocarcinoma cell line (A549). DFMO showed a dose-dependent growth-inhibitory effect against human colon tumor xenograft and lung adenocarcinoma cells. Growth-inhibitory activity of DFMO against T6 cells was reversed completely when the cells were treated simultaneously with putrescine (PU) (10(-6) M) and DFMO (10(-3) M). When 5-FU and DFMO were used in combination against T6 cells, no antagonism or synergism between the two drugs was seen. However, in the case of A549 cells, when DFMO was used in combination with DX, there was a consistent increase in growth inhibition that surpassed the inhibition of either agent given alone. PMID- 1890837 TI - Five-year survival for cisplatin-based chemotherapy versus single-agent melphalan in patients with advanced ovarian cancer and optimal debulking surgery. AB - The purpose of this study was to evaluate 5-year survival and 5-year progression free survival in previously untreated patients with advanced ovarian cancer treated with single-agent melphalan in which very few patients underwent optimal debulking surgery (less than 2 cm residual) as compared with the patients treated with Cisplatin-based chemotherapy in which most patients underwent optimal debulking surgery. Significant increases in 5-year survival and 5-year progression-free survival were noted as we changed from the melphalan trial, in which only 14% underwent optimal debulking surgery, to PAC-H, in which 57% and the PAC trial in which 90%, respectively, underwent optimal debulking surgery. However, for those patients whose tumors were optimally debulked in the three trials, there were no statistically significant differences in median survival, median progression-free survival, 5-year survival, or 5-year progression-free survival in those patients treated with melphalan, PAC-H, or PAC. Without optimal debulking surgery, Cisplatin-based multiagent chemotherapy offered a small survival advantage. These results are similar to that reported by Gruppo Interregionale Cooperativo Oncologico Ginecologia, in which survival curves were identical for all the subgroups of chemotherapy regimens for those patients with residual disease less than 2 cm at the onset of chemotherapy whether they received (1) cyclophosphamide; (2) cyclophosphamide and Adriamycin; (3) cyclophosphamide, Adriamycin, and Cisplatin; (4) cyclophosphamide, Adriamycin, and hexamethylmelamine; (5) Cisplatin and cyclophosphamide; (6) low-dose Cisplatin; (7) high-dose Cisplatin; or (8) carboplatin. PMID- 1890838 TI - Patterns of DNA-ploidy in operable colorectal carcinoma: a prospective study of 100 cases. AB - A prospective study of cellular DNA content was made by means of flow cytometry in a nonconsecutive series of 100 patients undergoing surgery for primary colorectal adenocarcinoma. DNA-aneuploidy was present in 80% of cases (80/100); 39% of these were multiclonal (31/80). There was no significant correlation between DNA-ploidy and the clinical and pathological features examined, except for the primary tumor site (right colon vs. left colon vs. rectum: P less than 0.001). After a minimum follow-up of 30 months, out of 40 patients with no local invasion and/or distant metastases, 100% (9/9) of those with DNA-diploid neoplasias showed no signs of disease relapse, vs. 55% (17/31) of the DNA aneuploid cases (P less than 0.05). Furthermore, in 45 cases with a minimum follow-up of 30 months, overall survival was 90% in patients with DNA-diploid carcinomas and 43% in the DNA-aneuploid cases (P less than 0.05). PMID- 1890840 TI - Results of multimodal therapy in Ewing's sarcoma: a retrospective analysis of 20 patients. AB - A retrospective analysis was performed of 20 patients with Ewing's sarcoma treated by combined modality therapy, consisting of surgery, radiotherapy, and chemotherapy. Fourteen patients (70%) achieved complete remission and 5 patients (25%) were in partial remission at the end of treatment. One patient (5%) failed to respond to combined modality therapy. The overall 5 year actuarial survival was 64% and the disease free survival, 55%. Persistent or recurrent disease occurred in 8 patients (40%); one of them was salvaged by surgery and chemotherapy. Site and extent of primary lesion were prognosticators of patients' outcome. One patient developed radiation-related-sequelae. The efficacy of aggressive management consisting of wide surgery, radiotherapy and intermittent high dose chemotherapy is discussed. PMID- 1890839 TI - Effects of antiplatelet agents alone or in combinations on platelet aggregation and on liver metastases from a human pancreatic adenocarcinoma in the nude mouse. AB - There is ample evidence to suggest that hematogenous metastasis may be related to the ability of tumor cells to promote aggregation of host platelets. Arachidonic acid metabolism in platelets and vessel walls may also contribute to the metastatic process. Several preliminary trials of platelet inhibitory agents have been performed. Ketoconazole (inhibitor of lipoxygenase and thromboxane synthetase), verapamil (calcium antagonist), forskolin (stimulator of platelet adenylate cyclase), and indomethacin (inhibitor of cyclooxygenase) were examined, alone and in combination, to investigate their effects on platelet aggregation and on hepatic metastases from human pancreatic tumor cells (RWP-2) in nude mice. The tumor cells were injected intrasplenically, and the animals were divided into control, single-drug and combination treatment groups. The agents were administered intraperitoneally 1 hr before and every 24 hr after the tumor cell injections for 6 days. Statistically significant differences were observed between the control and single-treatment groups on the reduction of liver tumor nodules (range P less than 0.001-0.032) and in the liver surface areas occupied by tumor (range P less than 0.001-0.013). Furthermore, when these agents were combined, similar reductions in liver tumor nodules were noted (range P less than 0.001-0.008), while even greater inhibitory effects were seen in the liver surface areas occupied by tumor (P less than 0.001) compared with the single treatment groups. Also, the combination studies strongly inhibited RWP-2-induced platelet aggregation in human platelet-rich plasma. PMID- 1890841 TI - Lymphoepithelioma-like carcinoma of the lung. AB - Historically lymphoepithelioma was a term used to describe an undifferentiated mucosal carcinoma with a lymphocytic component arising only from the nasopharynx, although recently, lymphoepithelioma-like carcinoma has been found to occur as a primary tumor of the lung. Thus far, five patients have been documented as having this rare anatomical presentation. The patient that is being presented is the latest case of lymphoepithelioma-like carcinoma of the lung and will be compared clinically and histologically with the other four cases. The case is presented in order to discuss optimal methods of diagnoses and treatment for this condition. PMID- 1890842 TI - Benign cartilaginous tumors of the upper airway. AB - Benign cartilaginous neoplasms of the laryngotracheal apparatus are uncommon clinical entities. Two cases of cartilaginous lesions of the upper airway are reported. Resection with maintenance of upper airway structural integrity is the preferred treatment. Temporary tracheostomy is often necessary and can provide access for stenting of the tracheal repair. PMID- 1890843 TI - Special memorial issue--David Garfinkel (1930-1990). PMID- 1890844 TI - A computer model of pancreatic islet glycolysis. AB - We have modeled an experiment with perifused pancreatic islet cells using our BIOSSIM language. The experiment and the resulting model are concerned with glucose uptake and glycolysis by the beta-cells of pancreatic islets. Although glycolysis appears to be involved in insulin release, we do not have enough information to represent insulin release in detail. The rapid entry of glucose into the beta-cell is promoted by a carrier having a very high tissue capacity. Phosphorylation of glucose by the low affinity enzyme glucokinase appears to be limiting for glycolysis. The effects of several hexose diphosphate activators of phosphofructokinase are modeled. Model behavior is described. The kinetic parameters of the enzyme submodels are given. Because of the difficulties of preparing large amounts of experimental material, information on pancreatic islet metabolism is limited. This model is a plausible explanation of the experimental results. Recent work on the genetically engineered glucose transporter and glucokinase is discussed. PMID- 1890845 TI - A thermodynamic and biomechanical theory of cell adhesion. Part I: General formulism. AB - The equilibrium thermodynamics calculus of cell adhesion developed by Bell et al. (1984, Biophys. J. 45, 1051-1064) has been extended to the general non equilibrium case. In contrast to previous models which could only compute the end results of equilibrium states, the present theory is able to calculate the kinetic process of evolution of adhesion, which may or may not approach towards equilibrium. Starting from a basic constitutive hypothesis for Helmholtz free energy, equations of balance of normal forces, energy balance at the edge of the contact area and rate of entropy production are derived using an irreversible thermodynamics approach, in which the restriction imposed by the Second Law of Thermodynamics takes the place of free energy minimization used by Bell et al. (1984). An explicit expression for adhesion energy density is derived for the general transient case as the difference of the usable work transduced from chemical energy liberation from bond formation of specific crosslinking molecules and the repulsive potential of non-specific interactions. This allows the energy balance to be used as an independent boundary equation rather than a practical way of computing the adhesion energy. Jump conditions are obtained from the conservation of crosslinking molecules across the edge of adhesion region which is treated as a singular curve. The bond formation and lateral motion of the crosslinking molecules are assumed to obey a set of reaction-diffusion equations. These equations and the force balance equation within the contact area, plus the jump conditions and the energy balance equation at the edge form a well-posed moving boundary problem which determines the propagation of the adhesion boundary, the separation distance between the two cell membranes over the contact area as well as the distributions of the crosslinking molecules on the cell surfaces. The behavior of the system depends on the relative importance of virtual convection, lateral diffusion and bond formation of the crosslinking molecules at the edge of the adhesion region, according to which two types of rate limiting cases are discussed, viz, reaction-limited and diffusion-limited processes. PMID- 1890846 TI - Identification of regulatory properties of metabolic networks by graph theoretical modeling. AB - An earlier graph theoretical model of metabolic and gene-expression networks has been modified and extended to include the effect of electrical potentials on binding constants, representation of uncatalyzed processes, and treatment of parallel reactions catalyzed by a single enzyme. Formal operations on the graph, which are facilitated by a set of standardized guidelines, identify the feedback signals in the network and rank them according to their influence. The technique was applied to a model of glycolysis in ascites tumor cells in the absence and presence of 12.5 mM exogenous glucose. Feedback regulation was widely distributed and mostly due to binding of adenine nucleotide cofactors to the enzymes of the network. The major changes in feedback regulation on adding glucose is the relief of inhibition of hexokinase and phosphofructokinase and the activation of pyruvate kinase. We conclude that regulation of tumor cell glycolysis is not restricted to hexokinase or to (Na+,K+)-ATPase as was previously suggested by others. PMID- 1890847 TI - An improved mathematical model of hormone secretion in the hypothalamo-pituitary gonadal axis in man. AB - We propose an improved mathematical model for the secretion in the hypothalamo pituitary-gonadal axis. We think this model is more reasonable than any previous one and can interpret a large number of experimental facts. PMID- 1890848 TI - A mathematical model and computer simulation study of insulin receptor regulation. AB - A homeomorphic mathematical model of cell surface insulin receptor regulation is developed. The overall structure of the model is based on molecular mechanisms suggested by in vivo and in vitro experimental evidence from many different cell types. Model parameters correspond to cellular processes which are constrained by known boundry value conditions. As an example, computer simulation results are compared with published data from BC3H-1 myocytes in culture. With appropriate parameter choice, this model is able to simulate data from other cell types. Cellular processes which are explicitly represented in the model include: bound and unbound receptor endocytosis, receptor recycling, intracellular receptor degradation, and state-dependent receptor synthesis. Most of these processes are represented as first-order events. Using more complex representations of the model structure with higher order rate constants or saturable pathways does not qualitatively improve simulation results. Simulations are able to reproduce ligand-induced down and up regulation of receptors as well as the initial spontaneous display of surface insulin receptors. To demonstrate the behavior of our model and illustrate its utility for explaining insulin receptor regulation for a variety of conditions, simulations for which experimental data is unavailable for direct comparison are also shown. We believe the structure of our model is sufficient to explain insulin receptor regulation in a wide variety of cell types. In addition our model may aid in understanding the receptor component of insulin resistance (decreased sensitivity or responsiveness to insulin) seen in pathological states such as obesity and diabetes mellitus. Finally, this model may be applicable to the study of the regulation of other polypeptide hormone receptors. PMID- 1890850 TI - A mathematical model and computer simulation study of insulin sensitive glucose transporter regulation. AB - A mathematical model of insulin sensitive glucose transporter regulation is developed. Model structure is based on experimental evidence from adipocytes and myocytes. Model parameters correspond with known cellular processes. As an example, computer simulation results are compared with data from rat adipocytes. Cellular processes explicitly represented in the model include state-dependent glucose transporter synthesis and degradation rates, insulin sensitive glucose transporter translocation rates, and a glucose transporter endocytosis rate. Most of these processes are represented as first-order events. Using more complex representations of the model structure (e.g. higher order rate constants or saturable pathways) or alternative structures did not result in qualitatively better results. The model is able to accurately simulate the insulin sensitive, insulin concentration dependent, reversible translocation of glucose transporters observed in normal adipocytes. The model is also able to accurately simulate the changes in regulation of glucose transporter translocation observed with increases in cell surface area. Finally, the model can simulate pathogenic states which induce impairment of glucose transporter regulation (e.g. altered glucose transporter regulation in adipocytes from rats on high fat diets, rats with streptozotocin induced diabetes, and fasted rats). Since the structure of our model is sufficient to explain glucose transporter regulation in both normal and pathological states, it may aid in understanding the post-receptor components of insulin resistance (decreased sensitivity or responsiveness to insulin) seen in pathological states such as obesity and diabetes mellitus. PMID- 1890849 TI - Simulation of the voltage dependence of the Na, K pump applied to cardiac cells. AB - We use simulation to study the dependence of the Na, K pump on membrane potential. Two consecutive mechanisms for the Na, K pump, based on a reduced Post Albers scheme, are examined: one with six steps called GV3 and one with seven steps called MGV3. In GV3, a single voltage-dependent step combines both Na+ translocation and Na+ release into the extracellular medium. In MGV3, these two processes are allocated to two separate consecutive steps, but only the Na+ translocation step is voltage-dependent. Using the optimization software SCoPfit, numerical values of rate coefficients, symmetry factor (beta), and pump site density were found by fitting the models to published experimental data so that both GV3 and MGV3 could quantitatively reproduce steady-state current-voltage relationships for both forward and backward running of the pump, as well as [Na+]in and [K+]out activation curves. Using the rate coefficient values found by SCoPfit, we simulated a voltage-clamp experiment with both models running under their Na(+)-Na+ exchange mode, and we computed the transient currents generated following voltage steps in both depolarizing and hyperpolarizing directions from a basic potential of -40 mV. The voltage dependence of the rate constant (1/tau) of decay of the transient currents could qualitatively be reproduced when beta = 0.884 for GV3, and 0.932 for MGV3. The quantitative discrepancy between published experimental data and the theoretical curve generated by GV3 at potentials more negative than -20 mV was considerably reduced by using model MGV3. This finding alone suggests that a more detailed mechanism containing a single voltage dependent step may reproduce all major steady-state and transient characteristics of the Na, K pump without the need of a second voltage sensitive step. However, the quantitative discrepancy between published experimental data and the theoretical curve generated by MGV3 at potentials more negative than -60 mV may be fully removed if either beta itself is voltage-dependent, or if a second voltage-dependent step is included in the model. PMID- 1890851 TI - What is resource partitioning? AB - The concept of resource partitioning, as originally developed, relates to evolutionary change in species in response to selection pressures generated by interspecific competition. More recently it has taken on another meaning, one that is not defined in terms of evolutionary function, and which refers simply to differences in resource use between species regardless of the origins of the differences. Such a shift in usage has several drawbacks for ecological theory, which are discussed. Of most practical significance to ecologists is the inappropriate justification conferred on the continued use of a category that contains characters that are not equivalents. Ecologists are therefore frequently in the position of explaining the presence of species in an area by reference to the by-products of their adaptive evolution. PMID- 1890852 TI - A unifying mathematical analysis of methods to estimate rumen volume using digesta markers and intraruminal sampling. AB - A theoretical exposition of methods for estimating the quantity of digesta in the rumen using digesta-flow markers and intraruminal sampling is given, with emphasis on the kinetic assumptions underlying each method. Single- and dual marker approaches to estimating volume in steady and non-steady-state are presented. PMID- 1890854 TI - A stochastic branching model with formation of subunits applied to the growth of intestinal crypts. AB - The intestinal epithelium is one of the most rapidly regenerating tissues in mammals. Cell production takes place in the intestinal crypts which contain about 250 cells. Only a minority of 1-60 proliferating cells are able to maintain a crypt over a long period of time. However, so far attempts to identify these stem cells were unsuccessful. Therefore, little is known about their cellular growth and selfmaintenance properties. On the other hand, the crypts appear to exhibit a life cycle which starts by fission of existing crypts and ends by fission or extinction. Data on these processes have recently become available. Here, we demonstrate how these data on the life cycle of the macroscopic crypt structure can be used to derive a quantitative model of the microscopic process of stem cell growth. The model assumptions are: (1) stem cells undergo a time independent supracritical Markovian branching process (Galton-Watson process); (2) a crypt divides if the number of stem cells exceeds a given threshold and the stem cells are distributed to both daughter crypts according to binomial statistics; (3) the size of the crypt is proportional to the stem cell number. This model combining two different stochastic branching processes describes a new class of processes whose stationary stability and asymptotic behavior are examined. This model should be applicable to various growth processes with formation of subunits (e.g. population growth with formation of colonies in biology, ecology and sociology). Comparison with crypt data shows that intestinal stem cells have a probability of over 0.8 of dividing asymmetrically and that the threshold number should be 8 or larger. PMID- 1890853 TI - Mathematical model of cellular basis for the respiratory sinus arrhythmia. AB - The respiratory sinus arrhythmia (RSA) is a vagally mediated oscillation in cardiac cycle length at the frequency of breathing. We developed a mathematical model that predicted the temporal and frequency dependence of the RSA. We used the mathematical model to examine the underlying cellular basis for the RSA at the level of the sinus node. We alternated efferent vagal activity between a low and a high frequency at the frequency of breathing. This oscillation caused the rate of acetylcholine (ACh) release to oscillate between a low and a high rate at the frequency of breathing. ACh degradation followed linear pharmacokinetics for physiological concentrations of ACh. Therefore, the concentration of ACh in neuroeffector junctions of the sinus node oscillated at the frequency of breathing. Membrane potential responded rapidly to changes in the concentration of ACh relative to the rate of ACh degradation. Thus, the time course of the RSA depended on the rate of ACh degradation. Membrane potential oscillated at several integer multiples of frequency of breathing and at various higher frequencies, which were integer multiples of the frequency of breathing and the frequencies of firing of the sinus node. However, computing cardiac cycle length from membrane potential eliminated the higher frequencies. Therefore, cardiac cycle length oscillated at several integer multiples of the frequency of breathing, but not at these higher frequencies. PMID- 1890855 TI - A theory for analysis of cell populations with non-cycling S phase cells. AB - Analyses of cell populations that have been labeled in vivo with analogs of thymidine that are incorporated by cells synthesizing DNA and then monitored over time by bivariate flow cytometry sometimes detect populations of cells that have S phase DNA content but that have not acquired label. Two alternative explanations for the lack of labeling are that either the cells were not exposed to the label or that the cells stopped DNA synthesis and ceased progression through S phase. To help determine which scenario is the more likely, a model has been devised for studying a population of cells that includes the possibility that cells in S phase will cease DNA synthesis. In this model, the initial fraction of unlabeled cells in S phase depends on two rates: the growth rate of the total population and the number of cells that cease progression through S phase per unit time. The model is used to analyze the changing quantities which can be measured by monitoring the population of cells over time and is used to estimate the two rates required to compute the initial fraction of unlabeled S phase cells. Thus, the initial fraction of unlabeled cells can be compared with that predicted by the population dynamics to determine whether one explanation for the failure of some cells to be labeled is preferable to the other, which in turn might offer information about tumor microvascular or cytologic properties. PMID- 1890856 TI - Entropy principle for human development, growth and aging. AB - Entropy productions within nude subjects in respiration calorimeters are calculated from the corresponding energetic data obtained by Du Bois et al. (1952, J. Nutr. 48, 257-293.). The entropy production for men is constant at environmental temperatures from 24-34 degrees C. The metabolic entropy production comprises 98.6% of the total entropy production. The entropy production for women shows a minimum at 30 degrees C (the middle of the neutral zone), a small rise in the cold zone and a trend toward a rise in the warm zone; the average entropy production for women is 8.7% smaller than that for men. The entropy production rises from 0-2 years of age, and decreases rapidly from 2-25 years of age and then gradually to 85 years of age. The entropy production does not seem to achieve a minimum or a level in the lives of men and women. Based on these results, a three-stage hypothesis of entropy production in human life is proposed. PMID- 1890857 TI - Sexual showiness and parasite load: correlations without parasite coevolutionary cycles. AB - Hamilton & Zuk (1982, Science 218, 384-387.) produced a model of sexual selection in which coevolutionary cycles of host and parasites generate consistently positive correlations between parent and offspring viability, and that animals choose mates for genetic disease resistance by scrutinizing characters whose full expression is dependent on health and vigour. They predicted a positive correlation between sexual showiness and parasite burden across species, and a negative correlation within a species. First, recent suggestions that interspecific correlations in the opposite direction to that indicated above are consistent with the mechanisms of Hamilton & Zuk's model are discussed. Second, it is shown that the model's predictions can be produced by heritable variation maintained by non-parasite fluctuating selection. In this case, the parasites associated with degree of sexual showiness are those able to amplify any initial heritable differences in vigour. Alternative sources of positive correlation between parent and offspring viability, which include the indirect effects of climatic change and exclude the need for host-parasite coevolutionary cycles, are also proposed. PMID- 1890859 TI - Ongoing studies on non-Hodgkin's lymphomas (NHL) within the EORTC lymphoma group. PMID- 1890858 TI - The F-MACHOP regimen in advanced diffuse aggressive lymphomas: summary of ten years' experience at a single institution. PMID- 1890860 TI - GM-CSF: clinical trials in non-Hodgkin's lymphoma patients with chemotherapy induced leucopenia. AB - Fourteen patients (M/F, 6/8; age, 48/23-64 yrs) with relapsing or primary resistant intermediate-high grade non-Hodgkin lymphomas were treated with ARA-C (2 g/m2 x 4 on days 1 and 2), DDP (100 mg/m2 96 hr infusion) and VP-16 (150 mg/m2 on days 1, 2 and 3). GM-CSF or placebo was administered from the 5th day until neutrophil count reached greater than or equal to 1000/microliters on 2 consecutive days. Three PR and 6 CR were documented. Two CR pts are still in CR at 19 and 23.5 months. With the exception of one case of cerebral haemorrhage, life-threatening liver toxicity, exfoliative colitis, capillary leak syndrome and anaphylactoid reaction, the protocol regimen provoked only modest haematological and extra-haematological toxicities. PMID- 1890861 TI - Immunoglobulin and T-cell receptor gene analysis in lymphoproliferative disorders. AB - The analysis of the configuration of the immunoglobulin (Ig) and T-cell receptor (TCR) gene regions has been of great relevance in defining conclusively the nature of several lymphoproliferative disorders in man. Furthermore, this technological tool has also helped to dissect between a monoclonal and polyclonal pattern of proliferation. The major results obtained, the potential use of molecular studies for the detection of minimal residual disease and the relevance of these techniques in the understanding of the processes of leukemogenesis and lymphomagenesis are discussed. PMID- 1890862 TI - Histopathology of bone marrow involvement in T-cell lymphomas. PMID- 1890863 TI - Diffuse large cell lymphoma. Prognostic factors with treatment. AB - Five successive chemotherapy protocols for stages II, III and IV diffuse large cell lymphoma (DLCL) have resulted in identical overall survivals. Between 35% to 45% of patients survived. In a multivariate analysis employing the Weibull model 3 factors were associated with shortened survival: bulky mediastinal and/or retroperitoneal disease, elevated serum LDH and advanced age. In young patients with bulky mediastinal and/or retroperitoneal disease and high serum LDH, autologous bone marrow transplantation following high dose chemotherapy and radiation therapy (RT) as part of the initial treatment have produced more promising results. In a randomized trial, a significantly longer disease-free survival was found for patients with stages I or IE diffuse lymphomas with RT followed by adjuvant chemotherapy than with RT alone. PMID- 1890864 TI - Clinical and pathological restaging in aggressive non-Hodgkin's lymphomas. AB - Residual tumor masses are sometimes found in non Hodgkin's lymphoma (NHL) patients after chemo-radiotherapy treatment. Radiologic findings do not differentiate lymphoma from fibrosis necrotic tissue. Surgical and histology reevaluation is the most reliable method of evaluation the viability of tumor residual masses. Sixty-three consecutive high-grade NHL were treated with F MACHOP regimen. After 3 courses of F-MACHOP the response was evaluated clinically: twenty two (36%) achieved a clinical complete remission, 32 a clinical partial remission, 7 were non responders and two were not evaluable. An early pathological response evaluation was performed in 23 clinical partial responders. Fifteen (65%) patients had no evidence of NHL after pathological restaging and were considered as pathologic complete response and completed treatment with 3 additional courses F-MACHOP. Eight (35%), histologically positive, were defined as pathologic partial response and were crossed to salvage regimens. The 1 year actuarial event-free survival differed significantly according to clinical response after 3 courses of F-MACHOP and the outcome of clinical partial responders was highly dependent on the result of pathological restaging (87% for negative and 23% for positive). Our experience suggests that a significant proportion of clinical partial responses are histologically confirmed at pathological restaging when this procedure is performed early during treatment. PMID- 1890865 TI - Autologous bone marrow transplantation for adult advanced stage lymphoblastic lymphoma in first CR. A study of the NHLCSG. AB - Fourty successive adult patients with lymphoblastic lymphoma entered a study of sequential chemotherapy consisting of an intensive LSA-L2-type protocol to induce first complete remission. Twenty-one patients in first CR (median age 24 years, range 15-43), after receiving a conditioning regimen consisting of cyclophosphamide and total body irradiation, underwent autologous bone marrow transplantation. At this time fourteen patients are alive and well 5-72 months post-transplant (median follow-up 58 months) with an actuarial disease free survival of 66%. These early results suggest that high-dose chemoradiotherapy followed by autologous bone marrow transplantation may improve long-term disease free survival in advanced stage adult lymphoblastic lymphoma. PMID- 1890867 TI - The Stanford Hodgkin's disease (HD) studies--an update. AB - Successive, prospective clinical trials for adults with HD have been conducted from 1962-1991. With approximately 75% of patients in continuous remission as a result of current therapy, attention may be focused on reducing treatment complications for the majority of patients and improving efficacy in selected, high risk populations. This overview will describe recently completed and ongoing clinical trials at Stanford University which address these therapeutic objectives. PMID- 1890868 TI - Autologous bone marrow transplantation for aggressive non-Hodgkin's lymphoma: issues and controversies. PMID- 1890866 TI - Will doxorubicin-containing regimens replace MOPP and its variants? PMID- 1890869 TI - The problem of purging for ABMT in non-Hodgkin's lymphoma. PMID- 1890870 TI - Nine years' experience with ABMT in 128 patients with Hodgkin's disease: an Italian study group report. AB - One-hundred, twenty-eight patients with Hodgkin's disease in remission or who had failed a mechlorethamine, vincristine, procarbazine and prednisone (MOPP), a doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) and/or lomustine, etoposide and prednimustine (CEP) regimens have been treated with a high-dose therapy (HDT) containing cyclophosphamide, etoposide, carmustine (CVB) and autologous bone marrow transplantation (ABMT). Forty patients were treated while they were in resistant or progressive disease states using alternating MOPP/ABVD protocol; 15 patients received ABMT in first relapse; 51 patients had a complete remission (CR) with first-line therapy but later relapsed and then received conventional salvage therapy; 16 achieved no response or progression ("resistant relapse" patients) and 35 responded partially or completely ("sensitive-relapse" patients). The other 22 patients received ABMT in remission. Following HDT, 56 patients (52.8%) achieved CR and 23 patients (21.6%) achieved a partial remission for an overall response rate of 74.4%. Sixteen patients failed to respond and died in progressive disease 1 to 10 months (median 6 months) after ABMT. High dose therapy produced severe toxicity including vomiting (100%), mucositis (75%) and liver enzymes and alkaline phosphatase elevations (51%). There were 10 treatment-related deaths. A multivariate analysis identified poor performance status and resistant-relapse patients as very important adverse risk factors for survival immediately after ABMT. These results, while validating this procedure for inducing remissions in advanced highly-treated patients, at the same time confirm the need of employing this approach in first relapse or in second complete remission after standard therapy and before ABMT or, in first complete remission in very high risk Hodgkin's disease patients. Our experience in 15 very poor prognosis Hodgkin's disease patients transplanted in first CR demonstrated to be much significant. PMID- 1890871 TI - Proto-oncogene and tumor suppressor gene involvement in human lymphomas. PMID- 1890872 TI - Lymphomas in the elderly. AB - The elderly patients with lymphoma suffer from a relevant excess mortality, both during treatment and in the course of follow-up: various causes contribute, including: 1) "generational" mortality; 2) iatrogenic mortality due to unexpected organ/system fragility; 3) low remission rates, due to low tolerated doses and, 4) a high prevalence of second tumors. The difficulty in achieving high cure rates begins after age 50 and steadily increases for patients over 60, 70 and 80. Less aggressive staging procedures are justified, and the modern visualizing techniques provide alternatives to lymphangiography and laparosplenectomy. In HD, local radiation instead of Total Nodal Irradiation, and doses of 30 or even 20 Gy may be administered for stages I and II; for stages III and IV the ChlVPP and the NOVP or the "ABVD without D" regimens may be adopted. After chronological and/or biological age 80, sequentially administered single agents produce an effective palliation, allowing for a good quality of life during treatment, and often obtain a reasonable prolongation of survival. Many NHL of elderly patients are indolent in their course, and a "watch and wait" policy is often in the true interest of the patient; when local aggressiveness only is apparent, a local low dose radiation may be considered. For advanced stage, treatment-requiring low grade-NHL, oral chlorambucil plus or minus low dose steroids (or prednimustine) should be considered in alternative to watch and wait. For high grade, aggressive NHL, chemotherapy with short, non-Methotrexate-containing programs like POCE, NOSTE, P-VABEC, or other variations of MACOP-B are acceptable. Beyond age 80, or when other factors deteriorate the chances for survival, single agents like VM 26, or simple combinations of VP 16 + Prednimustine or VP 16 and Mitoxantrone may be adopted. PMID- 1890873 TI - Burkitt's lymphoma/leukemia: a clinicopathologic study on 24 adult patients. AB - We have retrospectively analyzed the characteristics of 24 adult patients affected with non-endemic Burkitt's lymphoma (BL) and Burkitt cell acute leukemia (L3 ALL). The median age of the entire group was 29 years with a male preponderance (75%). Median LDH value was 580 mU/mL. Test for HIV-antibodies was carried-out in 16 patients; 5 of them (21%) showed HIV positive. CNS was involved in 25% of patients at diagnosis. In all cases studied for karyotype, the t(8;14) translocation was evident. As to therapy, 5 patients were not evaluable for early death, 12 were given an intensive ALL program, 5 a cyclic chemotherapy and 2 a new protocol alternating high-dose cyclophosphamide, high-dose cytarabine with mitoxantrone and the CHOP regimen. The overall complete remission rate was 42%; among 7 remitters, 4 have relapsed so far within a median time of 6 months. Three of 13 (23%) patients with lymphoma presentation are long remitters and may be cured; all cases had stage II disease and low LDH at diagnosis (less than 250 mU/mL). No patients with Burkitt's leukemia survive. CNS disease (8 cases) and septic shock (6 cases) were the most frequent terminal events. In our experience, the prognosis of advanced stage BL and L3 ALL in adults does remain dismal; the high prevalence of CNS disease and HIV-positivity may have contributed to the poor outcome. PMID- 1890874 TI - Evaluation of age-related changes of physicochemical properties and functional activity of rat adipose plasma membranes and their possible relationship. AB - Studies were carried out to evaluate structural state of adipose plasma membranes (PM) from mature adult and aged Wistar rats and its possible relation to functional changes in aging. PM lipids were probed by fluorescence of 1,6 diphenyl-1,3,5-hexatriene (DPH) and pyrene. The data on DPH anisotropy, pyrene excimerization and induction resonance energy transfer (IRET) from PM proteins to pyrene provided the evidence for age-dependent decrease in PM lipid phase fluidity inclusive of that of annular lipid. Interaction between PM lipids and integral proteins also changed in aging. The observed structural changes were due to age-related lipid compositional modification. Evidence for this conclusion was provided by the following data: (i) DPH anisotropy was increased in aging both in PM and liposomes from the same PM lipids; (ii) both saturation/unsaturation fatty acid ratio and relative content of phosphatidylethanolamine (PE) increased in aged PM, whereas cholesterol/phospholipid and lipid/protein ratios were age independent; (iii) PM polypeptide composition remained practically unchanged during aging. Age-related changes of the PM structure were accompanied by a twofold decrease of high affinity insulin binding sites and elevation of their affinity to insulin. It was suggested that age-related changes of physicochemical properties of PM lipid phase might affect protein molecular conformation and function through either changes in bulk lipid fluidity or through specific lipid protein interactions. PMID- 1890875 TI - Cell cycle analysis in bone marrow and kidney tissues of dietary restricted rats. AB - The effect of dietary restriction (DR) on the proportion of cells in various phases of the cell cycle as determined by flow cytometry was investigated in the bone marrow and kidney of young and old Fischer 344 rats. Control rats were fed a standard occurrence of numerous age-associated diseases, including cancer, renal diseases and by the control rats starting at 16 weeks of age until killed at 5 or 20 months old. The relative proportion of cells in the various phases of the cell cycle was independent of tissue type, treatment condition and age, consistently showing an order of G1- greater than S- greater than G2M-phase. In old rats DR did not affect cell cycling in bone marrow of either sex, however, it did cause an increase in the percentage of G1-phase cells in the kidney of male rats. Additionally, DR caused a mathematically significant change in the percentage of cells in all phases of the cell cycle in the bone marrow of young male rats but had no effect in young females. The percentage of S-phase cells in both tissues of both sexes decreased in old rats when compared to young rats regardless of treatment conditions, indicating a parallel decline in cell proliferating activity with aging. To summarize, DR produces a greater cell cycle effect in the young male than the old male rats. Proliferative capacity is enhanced when the young male rats are dietary restricted. This may aid in DNA repair mechanisms and/or immune system response. PMID- 1890876 TI - Age-associated changes in antioxidants and antioxidative enzymes in rats. AB - The antioxidative defence capacity was assessed in tissues from different groups of rats at 3, 12 and 24 months of age. It was observed that the levels of antioxidants, vitamin E and ascorbic acid decreased in serum without any changes in liver; whereas reduced glutathione showed lower levels in both serum and liver with advancing age. Antioxidative enzymes such as superoxide dismutase and catalase activities did not indicate appreciable changes in hepatic mitochondria, but were observed to point out divergent trends in post-mitochondrial supernatants, superoxide dismutase showed reduced activities and catalase activities enhanced with age. PMID- 1890877 TI - Aging in brown fat: antioxidant defenses and oxidative stress. AB - Brown adipose tissue (BAT) responds to physiological stimulation with high rates of mitochondrial O2 consumption, and with high rates of lipid turnover. These are the most susceptible molecules to peroxidation. Thus, it is important to elucidate the changes in antioxidant defenses and lipid peroxidation that occur in this tissue during the lifetime of the individual. It is shown for the first time that during development from young (3 months) to mature adults (9 months) quantitatively important increases of all the antioxidant enzymes (superoxide dismutase, catalase, selenium dependent and independent glutathione peroxidases and glutathione reductase) take place in BAT. This is concordant with the much higher aerobic capacity and sensitivity to in vitro peroxidation of the tissue in mature adults than in the young. During aging (from 9 to 28 months of age), aerobic capacity is clearly reduced. Nevertheless, the sensitivity of BAT to in vitro peroxidation is maintained in old animals and, accordingly, the antioxidant defensive systems do not show important changes either. PMID- 1890878 TI - An unexpected periodicity among the prevalences of human age-related, mortal diseases. AB - A periodic pattern was discovered among the relative number of deaths per year for the major age-related diseases in humans. This pattern was observed among 178 causes-of-death composed of male and female. White (U.S.A.), Black (U.S.A.) and Japanese (Japan) populations. Both descriptive (Fourier transform) and statistical analysis procedures revealed evidence that the pattern resulted from the presence of an underlying power progression between disease prevalences, with a factor of approximately 2.0 between sizes. This periodicity was highly unlikely to have occurred by chance (P much less than 0.01). The presence of such a power progression suggests that the sizes of the various fractions of the total population, that are afflicted with these mortal diseases, are determined by forces intrinsic to the population and probably result from a common mechanism. PMID- 1890879 TI - Altered membrane anisotropy gradients of plasma membranes of living peripheral blood leukocytes in aging and Alzheimer's disease. AB - Several reports have suggested that membrane rigidity, a term that refers to the relative motion of membrane constituents, is decreased in Alzheimer's Disease. Accordingly, a series of fluorescent membrane probes was used to evaluate the rigidity from the surface to the center of the outer hemi-leaflet of the plasma membrane of living neutrophils, monocytes and lymphocytes. Anisotropy, a parameter which increases with increasing membrane rigidity, was calculated from flow cytometric measurements of vertically and horizontally polarized components of the fluorescence emission of the probes. These preliminary experiments suggest that whereas membrane rigidity in certain regions of the plasma membrane of peripheral blood leukocytes is increased as expected in elderly controls, it is decreased in Alzheimer's disease. PMID- 1890880 TI - Elevated concentrations of beta-nerve growth factor in selected tissues from senescence-accelerated mice (SAM-P/8). AB - Levels of the beta-subunit of nerve growth factor (beta-NGF) were determined in various tissues from senescence-accelerated mice (SAM-P/8) and compared with those from senescence-resistant control mice (SAM-R/1) at 4 months of age. (1) In SAM-P/8, the testis was 30% larger in terms of wet weight than that from SAM-R/1, whereas the adrenal glands from males and females were smaller than those from the respective controls by 45% and 20%, respectively. (2) About 70% of SAM-P/8 individuals had high concentrations of testosterone in serum (greater than 5ng/ml). (3) In SAM-P/8, endogenous levels of beta-NGF were significantly higher in the adrenal gland (20 and 7 times higher on average in males and females, respectively), in the thymus (100 and 5 times higher in males and females, respectively) and in the testis (500 times higher) than those in the control tissues. In other tissues there were little or no differences in terms of levels of beta-NGF. (4) Morphological changes in the adrenal gland, thymus and testis of SAM-P/8 mice were not as marked as expected from the elevated levels of beta-NGF in these tissues. (5) These results show that, in SAM-P/8 mice at 4 months of age, an elevation in the endogenous level of beta-NGF has already occurred in some peripheral tissues before senescence becomes accelerated. PMID- 1890881 TI - A comparative study of succinate-supported respiration and ATP/ADP translocation in liver mitochondria from adult and old rats. AB - This study was undertaken to compare the rates of succinate-supported hepatic mitochondrial respiration between 12 months (adult) and 29 months (old) male Fischer 344 rats. Experiments were also performed to determine the activity of adenine nucleotide translocase and the effect of its inhibition on mitochondrial respiration. Succinate-supported state 3 mitochondrial respiration was found to decline 20% between 12 and 29 months of age in rat liver, along with a similar 25% decrease in the respiratory control ratio with age. Adenine nucleotide translocase activity is shown to decrease 39% from adult to old rat liver mitochondria. This decrease does not, however, account for the decline in state 3 respiration, since translocase activity is approximately 50% greater than state 3 respiration in both adult and old rats. Therefore, adenine nucleotide translocase is not rate-limiting for state 3 mitochondrial respiration. Neither the rate of succinate permeation into the mitochondrial nor the rate of electron transport is rate-limiting for state 3 respiration, indicated by the greatly increased oxygen consumption with addition of the uncoupler carbonyl cyanide m-chlorophenyl hydrazone (m-CCCP). These processes, therefore, are not responsible for the observed decline in state 3 respiration. The implications and possible cause of the age-related decrease in the maximal rate of ATP-synthesis are discussed. PMID- 1890882 TI - Decline in histone H5 phosphorylation during erythroid senescence in chick embryos. AB - Previous studies have implicated histone H5 dephosphorylation as a causal factor in genetic inactivation and chromatin condensation during erythroid senescence in adult chickens. We show that histone H5 phosphorylation declines in two stages as various cohorts of erythroid cells senesce in chick embryos. The first decline occurs between 5 and 6 days and coincides with the senescence of primitive erythrocytes. The second decline in H5 phosphorylation occurs between 17 and 19 days of chicken development, when the definitive erythrocytes undergo senescence and chromatin condensation. These results point to a role for histone dephosphorylation during the programmed senescence of erythroid cells. PMID- 1890883 TI - Tail-cuff detection of systolic hypertension in different strains of ageing rats. AB - To identify rat strains suitable for studying age-related development of hypertension we compared pressures measured with the tail-cuff method in different groups of ageing Fischer 344, Wistar, or Sprague-Dawley rats. Preliminary experiments to establish optimal frequency of chronic blood pressure measurement in ageing rats showed that tail-cuff systolic pressures did not differ significantly whether taken weekly or monthly. Repeated tail-cuff measurements were comparable even when a common cuff size was used in different groups of rats with varying tail diameters. Additional studies were then carried out in 1-year old male Wistar and Sprague-Dawley rats to measure tail-cuff pressures monthly during the second year of age. Systolic and mean pressures increased progressively with age in both strains, as did body weight and heart rate, but the incidence of hypertension was higher in Sprague-Dawley than in Wistar rats. Elevations in mean pressures were sometimes more pronounced than those in systolic pressure. Two months after the last tail-cuff measurement, the presence of hypertension in Wistar rats was verified by the elevated mean pressures that were recorded from femoral artery catheters. Our results overall suggest that the predisposition to hypertension was higher in Sprague-Dawley than in Wistar or Fischer 344 rats of the same age, and also in males than in females of the same strain. Of all the different strains and sexes we compared, therefore, male Sprague-Dawley rats from 20 to 24 months of age may be the best model for studying the development of systolic hypertension with age. PMID- 1890884 TI - Soluble interleukin-2 receptor release defect in vitro in elderly subjects. AB - The evidence from several studies indicates that as individuals age, they may display immune dysfunctions, mostly T cell dysfunctions. Recently, a soluble form of the receptor for interleukin-2 (IL-2) (sIL-2R) has been demonstrated in human sera and in vitro stimulated culture supernatants from human T lymphocytes. In the present paper, we report in vitro sIL-2R production from peripheral blood mononuclear cells in elderly subjects. The results show that no difference exists for unstimulated cultures, whereas after mitogen stimulation the elderly subjects showed the lowest values compared with young ones. These findings suggest that sIL-2R may provide a new tool for the study of T lymphocyte dysfunctions in old age. PMID- 1890886 TI - Quantitative measurement of human physiological age by profiling of body fluids and pattern recognition. AB - Quantitative correlations with human age are demonstrated for 60 substances from a group of 200 substances measured in the urine of 235 men. Simplified pattern recognition calculations are used to combine these correlations into patterns of human age and to demonstrate their utility for the quantitative measurement of human physiological age and aging rate. The empirical use of these techniques for the extension of human life-span and diminution of human suffering from degenerative diseases is discussed. Current experimental limitations of this method are demonstrated and evaluated. The application of these techniques can form the basis for a significant advance in the quality of human life. PMID- 1890885 TI - Age related changes in anti-oxidative enzymes in cardiomyopathic hamster hearts. AB - Membrane abnormalities and a shortened life span are closely associated with the progressive cardiomyopathy of dystrophic hamsters. In the present work we investigate whether this membrane damage is associated with changes in the primary membrane defences (the anti-oxidative enzymes). We measured the levels of superoxide dismutase (SOD), glutathione peroxidase (GSH.Px), and catalase (CAT) in hearts of normal and cardiomyopathic (CHF 147) hamsters, aged 17 days to 12 months. In normal hearts all the enzyme activities follow a U-shaped curve: unweaned animals have 20-40% higher enzyme activities and 11-month-old hamsters 50-160% higher activities than adolescent or adult hamster hearts. Changes in this age-related pattern of enzyme activities are seen in dystrophic hearts in all but the 17-20-day-old animals. At 30 days of age and older, GSH.Px activities are decreased and SOD and CAT activities increased in cardiomyopathic hamsters compared to normal animals. SOD, while elevated, seems less affected than GSH.Px and CAT as the disease progresses. The changes in both absolute activities and ratio of activities of the anti-oxidative enzymes parallel the changes in the cardiomyopathic pathology. This work supports the view that the progressive cardiomyopathy of CHF 147 hamsters may be associated with changes in primary membrane defenses. PMID- 1890887 TI - Effect of dietary restriction and aging on polyploidy in rat liver. AB - Liver polyploidy levels were compared as a function of age and diet in male Fischer 344 rats between 1 and 24 months of age. Dietary restriction was imposed on one group by reducing their food intake to 60% of ad libitum food intake. Histological sections of the livers of animals at each age and diet were examined. Diploid, tetraploid and octaploid nuclei were observed, and their size and frequency established. There were no differences in the diameter or volume of these size classes as a function of age or diet. An age-related decline in the percentage of diploid nuclei, coupled with an increase in the percentage of tetraploid and octaploid nuclei was observed in both groups. The major difference between the two groups was that the adult level of liver polyploidy was attained more slowly in the animals on dietary restriction as compared to the ad libitum fed controls. Polyploid cell formation in the liver is under the control of growth hormone, thyroid hormone and thymus, all of which might be influenced by dietary restriction. PMID- 1890888 TI - Longitudinal Gompertzian analysis of lung cancer mortality in the U.S., 1968 1986. Rising lung cancer mortality is the natural consequence of competitive deterministic mortality dynamics. AB - Age-adjusted mortality rates for lung cancer (LC) in the United States from 1968 to 1986 were subjected to longitudinal Gompertzian analysis. Age-adjusted LC mortality rate distributions between age 20 and 50 years were determined by a variable environmental factor and a common intersect point. The environmental factor declined (improved) 1.89-fold for men and 3.11-fold for women in 1986 as compared to 1968. The age at the common intersect point was 47.2 years for men and 39.1 years for women. Between 1968 and 1986, the non-age-standardized annual crude LC mortality rate increased 44.8% for men and 217.6% for women. Longitudinal Gompertzian analysis of LC mortality data suggests that the rising LC mortality rates in the United States are the natural consequence of competitive deterministic mortality dynamics and not a reflection of an environment that is directly more conductive to LC mortality. That is, more people are dying of LC because they are not dying from other diseases such as ischemic heart disease and stroke. Longitudinal Gompertzian analysis demonstrates that single disease mortality should not be studied in isolation, but rather examined in relation to other causes of death. When viewed from this perspective, the basis for the more dramatic rise in LC mortality in women becomes immediately evident. PMID- 1890889 TI - Microfluorometric and fluorometric lipofuscin spectral discrepancies: a concentration-dependent metachromatic effect? AB - The fluorescent spectral patterns of some lipid peroxidation products and their derivatives have been investigated. A significant concentration-dependent fluorescence shift was found. A variety of suggested age pigment fluorophores, 1,4-dihydropyridines, Schiff base and MDA polymers, all demonstrated a potential for spectral shifts. Along with increased concentration, the fluorescence peaks of these fluorophores shifted from blue (400-490 nm) to golden-yellow or orange red (500-600 nm). The demonstrated metachromasia is supposed to be an inner filter effect resulting from molecular polymerization or stacking. Thus, the striking differences between lipofuscin fluorescence spectra obtained by different investigators may be explained as due to large differences in lipofuscin concentration during measurement with different techniques. The pigments are either studied in situ by morphologists and recorded by microscopic fluorometry or by biochemists using spectrofluorometers to measure the extracted and dissolved pigments. PMID- 1890890 TI - [Pituitary apoplexy and empty sella]. AB - Pituitary apoplexy (PA) is currently considered as one of the causes of empty sella (ES). However, in most reported cases the diagnosis of PA was based on anamnesis. A prospective study of three patients diagnosed during the PA episode was carried out. Periodical evaluations of hormone concentrations and cerebral computed tomography images were carried out. Initially, the three patients had a global anterior pituitary developed ES within 6 and 18 months. Surgical therapy was not undertaken in any case. Owing to the rarity of the disease definitive conclusions are difficult to obtain; however, the present study suggests that after an episode of PA global anterior pituitary failure develops, with subsequent ES. Early medical therapy with glucocorticoids can avoid surgical therapy. PMID- 1890891 TI - [Occupational lead poisoning]. PMID- 1890892 TI - [Patients fulfilling admission criteria who should not have been admitted]. PMID- 1890893 TI - [Clinical protocols]. PMID- 1890894 TI - [Acute endocarditis caused by Streptococcus pneumoniae serotype 2]. PMID- 1890895 TI - [Mean survival or survival rates?]. PMID- 1890896 TI - [Salmonella enteritidis and eggs: a never ending menace]. PMID- 1890897 TI - [Outpatient insulin therapy in type II diabetes: program evaluation and calculation of cost saving]. AB - BACKGROUND: Evaluation of the results of a program of outpatient insulinization in type II diabetes and the resulting saving in cost. METHODS: Data from 39 patients with that disease (mean age 62 years) were evaluated four months after the beginning of insulin therapy and diabetic education. The economic cost of the outpatient program was calculated and compared with the cost if patients had been admitted. RESULTS: A good metabolic control was achieved with a significant reduction (p less than 0.001) of the glycemic levels from 281 +/- 43 mg/dl (15.6 +/- 2.4 mmol/l) to 156 +/- 22 mg/dl (8.6 +/- 1.5 mmol/l). Fructose levels were reduced from 4.7 +/- 0.54 mmol/l to 3.29 +/- 0.51 mmol/l. Seventeen patients had some episode of mild hypoglycemia. The insulin dose was increased from 0.27 +/- 0.06 U per kg and day to 0.42 +/- 0.1 (11 patients required two insulin doses). At onset, no patient controlled the glycemia at home, while at the end of the program 46% did so. The evaluation of each educational end-point showed a mean of 4.8 +/- 0.3 (from 0 to 5); the end-point with the best score were the technical aspects. The economic cost of the program was 230.39 ptas per patient and day, versus 1351.75 ptas per patient and day if the patients had been admitted. CONCLUSIONS: Outpatient insulinization in type II diabetes has very good results and is economically effective provided the adequate equipment and facilities are available. PMID- 1890898 TI - [Somatometry and lipid profile in smokers. Modifications after smoking withdrawal]. AB - BACKGROUND: The purpose of this work was to determine the somatometric and lipidic profile in a group of 90 smokers and to carry out a prospective study on modifications due to smoking withdrawal. METHODS: A somatometric and lipidic profile was performed to 90 smokers and 30 non-smokers. Afterwards smokers were included in a smoking withdrawal program. One year later all subjects who stopped smoking as well as 10 of the smokers who failed in smoking withdrawal underwent a new blood analysis and somatometric study. RESULTS: Initial somatometry showed that smokers had a significantly higher (p less than 0.05) overweight and endomorphic index, based on somatometric characteristics. In addition, smokers showed significant lower level of HDL-cholesterol (high-density lipoprotein) than non-smokers (p less than 0.001). Somatometric and lipidic profile performed one year after smoking cessation showed a statistically significant increase on HDL cholesterol (p less than 0.05). Somatometric and lipidic profile of the subjects who failed in smoking withdrawal showed no significant changes in relation to the study made the previous year. CONCLUSIONS: From these data we suggest that modifications of lipidic profile induced by tobacco consumption can be reverted, at least in part, after smoking cessation. In addition smokers present higher overweight when theoretic weight is based on somatometric characteristics. PMID- 1890899 TI - [Evaluation of a program for the care of the diabetic. A 40-month continuity study]. AB - BACKGROUND: To evaluate the long term efficacy of a program of attention to diabetes mellitus. METHODS: A continued 40-month follow-up study in a group of 47 diabetic patients treated with insulin (21 type I and 26 type II) with a mean age of 45.8 years and a mean duration of diabetes of 8.1 years. These patients were seen in the hospital outpatient clinic during the initial 12 months and in community clinics during the remaining 12 months. RESULTS: Mean basal glycemia (7.4 +/- 1.5 mmol/l) and HbA1 (8.3 +/- 1.1%) at 40 months were significantly lower than those in the initial 12 months (8.8 +/- 2.4 mmol/l and 9.2 +/- 1.2%; p less than 0.001) and in the beginning of the study (4.2 mmol/l and 11.2 +/- 1.9%; p less than 0.0001). In type II diabetics, cholesterol and triglyceride levels showed a significant reduction from the mean first year levels (6.2 +/- 0.9 and 1.6 +/- 0.9 mmol/l) to those in the 12-40 months period (5.8 +/- 0.8 and 1.3 +/- 0.5; p less than 0.01 in both instances). Initially, 22 diabetics (46%) used rapid acting insulin; at the end, 37 had included these preparations in their treatment (78%; p less than 0.001). Only 7 patients (14%) used multiple insulin doses at the beginning. After 40 months, 29 (61%) were treated with 3-4 insulin injections per day (p less than 0.0001). In 43 patients (91%) no severe hypoglycemic crisis had developed. In 45 (95%) macroproteinuria was not detected and 40 (85%) had not developed microangiopathic lesions in the retina or microangiopathic involvement elsewhere as evaluated with the available techniques. Psychical depression was evaluated at 40 months using a semiquantitative scale questionnaire. The overall responses in the intervention group (n = 20; 25.4 +/- 4.6) showed lower depression levels (higher scores) than a control group ( n = 22; 22.4 +/- 4.9; p less than 0.02) constituted by diabetics with similar characteristics but who had not been following the program. CONCLUSIONS: The programs for the attention to the diabetic are effective in the long term to achieved and sustain metabolic control, the acquired knowledge and, to a sizeable degree, the compliance with therapy, provided that they integrate the teaching with the treatment. It is very likely that these programs reduce the risk of late features of the disease and the tendency to depression, independently from the place where the patient is controlled. PMID- 1890900 TI - [Occupational poisoning from metals]. PMID- 1890901 TI - [The cost of health]. PMID- 1890902 TI - [Critical review of drugs in 1990]. AB - New chemical entities approved abroad (43) and in Yugoslavia (37) were presented. Discussions on several "old" drugs (41) open at the Yugoslav Federal Drug Committee for any reason (new formulation, new dose, new packaging, dosage regimen or indication) and renewal of registration (114) were also included. Special attention was given to the drugs which had been refused the renewal of registration (8). Critical drug re-evaluation as an important element of the improvement of pharmacotherapy was emphasized. A total of 78 drugs was discussed or registered in 1990-1.28% of drugs from the group A (vancomycin), 10.2% from the group B (aclarubicin, dexfenfluramine, warfarin, alprazolam, colestipol, lovastatin, combination: cetrimonium + lidocain and estradiol vag.), 87.1% (the greatest number so far!) from the group C and 1.28% from the group D. Surveys of the most prescribed drugs in Zagreb, in Yugoslavia and in the world were also given having proved largely non-rational drug prescribing in this country. Further development of drug formulary concept was discussed, primarily for the drugs paid by the Health Insurance, as well as the unsatisfactory ADR reporting in Yugoslavia. Presented were also the activities of the Committee for Diagnosis, Pharmacotherapy and ADR of the Yugoslav Federal Institute for Health Protection. Publishing of Yugoslav daily defined doses is, according to the authors essential for further systematic monitoring of drug consumption on different levels in this country. It would be impossible to rationalize pharmacotherapy without these data. PMID- 1890903 TI - [Tonometry in the diagnosis of subclinical ophthalmopathy in patients with Basedow's disease]. AB - Ophthalmopathy in addition to hyperthyreosis with goitre and dermopathy is characteristic of Basedow's exophthalmos is frequently associated with elevated intraocular pressure (IOP) on upgaze. We wanted to examine whether these changes of IOP exist in patients with Basedow's disease without clinical manifestations of ophthalmopathy. We measured IOP with Goldmann's applanation tonometry in two positions: the primary position, when the patient looks straight ahead and then on upgaze. Forty-six patients with Basedow's disease were examined. The minority [5 (11%)] of the 46 patients had exophthalmos and 22 (47%) of them had abnormal IOP (delta IOP greater than or equal to 3 mmHg). The average interval between the onset of Basedow's disease and this study was 12.8 +/- 7.4 years for those patients who had exaggerated positional changes in IOP, as compared with 5.8 +/- 3.3 years for those with normal IOP, P less than 0.01. We conclude that Basedow's ophthalmopathy is more common than is recognized clinically and that ophthalmopathy is more frequent in patients suffering of Basedow's disease for a longer period. Measuring IOP in two positions is a very simple method which could help us in early diagnosis of ophthalmopathy in patients with Basedow's disease. PMID- 1890904 TI - [Prospective follow-up of ventricular septal defects and the incidence of their spontaneous closure in children]. AB - Over a period of three years, we have followed up children with congenital heart defect. They were followed up from the moment of birth. Ventricular septal defect (VSD) was diagnosed in 21 children (37.5%). Prevalent were the boys, 71.4%. Three children with ventricular septal defect died (14.3%), although the cause of death was not VSD. In nine children (42.8%), ventricular septal defect has spontaneously closed. On the basis of typical physical finding, electrocardiogram, chest X-ray and echocardiography, we concluded that five children had small, while four of them had medium ventricular septal defect. Eight children were found to have the VSD in the muscular and one in the membranous portion. Ventricular septal defect has spontaneously closed at the average age of 11.7 months. Prevalent were again the boys (66.6%). The mean birth weight of children with VSD was significantly lower at birth, as compared with the healthy ones (p less than 0.05). In nine children with VSD we have found past medical history data in the perinatal period, susceptible of exogenous and endogenous harmful effects on the growth development of embryo and maturation of organs in intrauterine life. Among the children comprised in that group, spontaneous closure of VSD occurred in 6 of them. PMID- 1890905 TI - [Mushroom poisoning with a long period of development]. AB - A group of 87 patients with the signs of poisoning with mushrooms with along period of incubation (t = 12.4 +/- 6.2 h) has been reported. Nausea, vomiting and diarrhea dominate in the clinical picture in the first phase and hepatic and/or renal insufficiency in the second phase. Forty-one patients (47.1%) had "only" clinical symptoms without severe parenchymatous impairments. Forty-six (54.9%) had evidence of a hepatic lesion and 8 patients (10.8%) had renal function impaired, 6 of which needed hemodialysis. There was a significant correlation between elevation of serum transaminases and prolongation of prothrombin complex, resulting from the decreased synthetic liver function (SGPT1/PV1r = -0.424, p = 0.00; SGOT1/PV1r = -0.448, p = 0.000) during the first days after poisoning. Hepatic and renal damage was not identical in all the cases, and there was no correlation between the elevation of serum transaminases and retention of nitrogen substances. When analysing the effect of therapy on elevation of serum transaminases and prolongation of prothrombin complex, a significant difference between elevation of serum transaminases and prolongation of prothrombin time was found in patients on competitive inhibition with penicillin or silibinin, as compared to the patients only on plasmapheresis (p = 0.004 for SGOT, p = 0.000 for SGPT). These data unquestionably suggest the efficacy of competitive inhibition in the treatment of poisoning with mushrooms of a long period of incubation. In favour of this therapy also speaks the group of seriously ill patients who were simultaneously on plasmapheresis and competitive inhibition and who had better improvement than those "only" on plasmapheresis (p = 0.004 for SGOT).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1890906 TI - [The status of care of abused and neglected children in Zagreb at the end of the 20th century]. AB - In this paper, the data on some medical, social and legal aspects of abuse and/or neglect of children in Zagreb are presented which, at least, partially illustrate this societies' care of mistreated children at the end of the 20th century. We reviewed questionnaires that were administered to 44 health institutions involved in the childrens' health control and/or treatment and to 14 social work services and analyzed cases of child mistreatment reported to the Zagreb Public Prosecution Office and final court judgements for 1987 to 1988. We conclude that all these institutions encounter cases of child abuse and/or neglect but that medical institutions identify only 10% of cases detected by social work services and that judicial system sentences with imprisonment about 30% of abusers. Underdetection of child mistreatment in Zagreb, in addition to poor coordination of services, are the possible reasons for insufficient concern for these children. Up to now, only mass media and scientific publications have spoken more loudly about this problem. The authors emphasize the need and obligation of all those professionals concerned with children and of the entire community to undertake relevant measures to protect abused and/or neglected children. PMID- 1890907 TI - [Hypersensitivity vasculitis caused by ethyl biscoumacetate]. AB - A case report of a 61-year-old patient with hypersensitive vasculitis caused by ethylbiscumacetate is presented. After the implantation of the artificial aortic valve the patient was treated with medigoxine, furosemide, dipiridamole, disopiramide, potassium chloride and ethylbiscumacetate. Among these drugs furosemide and ethylbiscumacetate are reported to cause hypersensitive vasculitis. On the basis of the past medical history, clinical and histological findings furosemide was ruled out as a causative agent. The diagnosis was confirmed by the skin biopsy and finding of a normal biologic activity of protein C. The discontinuance of all previous drugs and administration of methylprednisolone led to improvement in the skin lesions of the patient. The need for continuous anticoagulant therapy was the reason for fepromarone to be given, achieving good anticoagulant effect, without any side effects. According to the criteria of Karch and Lasagna the degree of connection between drug use and side effects in this case belongs to the category "probable". PMID- 1890908 TI - [Intracranial complications of sinusitis]. AB - A rare case of cerebral abscess is presented. Sinusitis was identified as a predisposing factor. Rhinogenous endocranial complications are almost ten times less frequent than the otogenous ones. Despite great progress in the treatment of infections of different localizations, the lethality from cerebral abscess has remained relatively high ranging between 30 and 60%. We report on one of our patients and give a critical review of the contemporary diagnostic and therapeutical possibilities in the treatment of cerebral abscess. The case is interesting since brain abscess has been completely cured inoperatively. Although the treatment of cerebral abscess has been considerably improved, this remains one of the most severe diseases, requiring further improvement of diagnostic and therapeutical methods. PMID- 1890909 TI - [Sepsis caused by Yersinia enterocolitica in a female patient with liver cirrhosis]. AB - As a primarily intestinal pathogen. Yersinia enterocolitica (Y. e.) may cause generalized infection in patients with malignant and other serious diseases or immunodeficient subjects. In certain conditions, elevated serum and tissue iron concentrations represent an additional risk factor for systemic infection with this opportunistic bacterium. In our patient, Y. e. septicemia developed during liver cirrhosis decompensation. Clinical signs of infection were alleviated by appropriate antibiotic therapy (gentamycin, cefuroxime), but as septicemia had been present for several days prior to therapy, it aggravated the patient's general condition, which entailed the development of hepatorenal syndrome and eventually lethal outcome. PMID- 1890910 TI - [Controlled comparison of nicardipine and propranolol in the treatment of arterial hypertension]. AB - A randomized collective comparative study between nicardipine (N) and propranolol (P) was conducted over a period of 7 weeks in thirty hypertensive patients of both sexes, aged from 20 to 65 years, with the diastolic pressure over 100, but below 120 mmHg. Thirteen examinees were given N (60-120 mg daily) and seventeen P (120-240 mg daily); the groups were comparable according to a series of relevant parameters. In the placebo-period the mean arterial pressure (MAP) was slightly lowered, by 4.4% (p greater than 0.20). MAP was, however, considerably lowered already at the end of the second week of active treatment both in the N group (from 135.1 +/- 7.4 to 116 +/- 10.8 mmHg, or by 19.1%; P less than 0.01), as well as in the P group (from 131.6 +/- 8.1 to 117 +/- 9.1 mmHg, by an average of 11.1%; P less than 0.05). The values continued to decrease, and at the end of the seventh week of the study MAP averaged 108.5 +/- 6.5 mmHg (-19.7%; P less than 0.01) in the N group, while it was 109.7 +/- 9.1 mmHg (-16.6%; P less than 0.01) in the P group. The heart rate became considerably slower in the P group only, from the initial 84.5 +/- 9.2 to 66.9 +/- 2.7 beats per minute at the end of the seventh week (-20.8%; P less than 0.01), but it was unexpectedly, although not significantly lowered also in the N group, from the initial 78.3 +/- 6.5 to 74.2 +/- 4.0 beats (-5.2%; P greater than 0.20).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1890911 TI - [Child abuse and neglect. I]. AB - In this review, published in two parts, the medical social and legal aspects of child abuse and neglect are assessed. The aim of this paper was to get all the physicians involved in the care of children more thoroughly acquainted with the extent, manifestations and management of abused and/or neglected children. The necessity of an organized multidisciplinary approach to this serious medical and social problem is also stressed. PMID- 1890912 TI - [The founding of the Medical School in Zagreb]. PMID- 1890913 TI - [Experimental surgery in the Republic of Croatia]. PMID- 1890914 TI - [Photosensitivity caused by drugs]. PMID- 1890915 TI - [Reference values for FVC and FEV1 in healthy adult nonsmokers]. AB - Reference values for FVC and FEV1 have been developed on a sample of 909 healthy adult nonsmokers, men and women, between the ages of 18 to 86 years. The examinees are the inhabitants of Korcula, Brac, Silba, Olib, Pag and the Peljesac peninsula. The lung function parameters were analysed as functions of height and age using full model multiple linear regression analysis. Comparisons with prediction equations for other equally selected populations indicated that even most commonly used equations in Yugoslav medical practice are inadequate for our data. Presently derived reference values are reliable and can be used in daily medical practice. PMID- 1890916 TI - [An expert system for differentiation of viral meningitis]. AB - The LOSTI system for viral meningitis differentiation, by using promptly accessible attributes, has been described. It is based on attribute values (averages and percentages). Logical principles on similarities and diversities are used. The system is dynamic for its ability to make itself permanently adjusted by using new cases and their attribute values. Through the possibility of prompt data processing according to a certain methodology, the system is able to take part in medical decision making. Its intention is not to make any definite decisions, just to "substitute" aetiologic diagnostics of viral meningitis in case it has not been successful or has not been done. It can also be used in epidemiological and statistical studies so long as the fact still stands that over half of the cases of serous meningitis remain aetiologically undiagnosed. PMID- 1890917 TI - [Factors contributing to the onset of heart rupture in acute infarct]. AB - The aim of this study was to find out the contributing factors for cardiac rupture in the course of acute myocardial infarction (AMI). Past medical histories and autopsy data of 80 patients were analyzed. The first group consisted of 30 patients who died due to heart rupture in the course of AMI and the control group of 50 patients who died from the other, more common complications of AMI. There was no difference between the groups according to age and sex of the patients. All patients who died from the rupture of the heart had a history of heavy chest pain, while it was lacking in 30% of the patients of the control group (p less than 0.01). All the first group patients showed electrocardiograms diagnostic for AMI, while it was lacking in 14% of the second group patients (p less than 0.05). Almost a half of the second group patients (47%) were in the class I of the Killip's classification, while only 20% of the control group did not developed left ventricular failure. Pathological study showed that the rupture of the heart most commonly occurred in the course of an anterior myocardial infarction. There was no difference according to the size of infarctions between observed groups, but the thickness of the left ventricular wall was significantly less (p less than 0.05) in the control group, and the heart weights were higher (p less than 0.05) in the control group. There was advanced atherosclerosis of the coronary arteries and about two thirds of the first group patients showed acute coronary thrombosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1890918 TI - [Comparison of lymphangiography and computerized tomography with staging laparotomy in patients with Hodgkin's disease]. AB - The staging procedure of Hodgkin's disease is vital for planning effective management. In this paper, the diagnostic value of lymphangiography (LAG) and computed tomography (CT), as compared with the findings of staging laparotomy (SL) is determined. Sixty-five patients with Hodgkin's disease have been studied: in 44 patients CT was performed, 13 underwent LAG and in 8 patients both methods (CT and LAG) were applied. In all 65 patients SL was undertaken. The findings showed that the lymphangiography accurately detected the extent of Hodgkin's disease in 31% of the patients and CT in 61%. Thus, the computed tomography is more effective in evaluating the disease than the LAG method, and moreover, it can be repeated. On the other hand, the lymphangiography, although less reliable, presents a lymph node structure. We conclude, on the basis of the obtained results that SL is the most useful method in staging of Hodgkin's disease. PMID- 1890919 TI - [The Brachmann-de Lange syndrome]. AB - On occasion of the 120th anniversary of Cornelia de Lange's birth, the recognized Dutch pediatrician, and the 40th anniversary of her death, we report a case with Brachmann-de Lange syndrome. The patient was hospitalised several times, immediately after the birth, within the 3rd year of life, and finally at the age of 13 years. The diagnosis was already established in the neonatal period by relevant symptomes. The phenotypical variations remained unchanged during that period and the patient presented with a great number of symptoms typical for this entity. The characteristics of the head and face were specially prominent, then the anomalies of the upper extremities and malrotation of the intestines. Since there is a great similarity with other syndromes, karyogram is indispensable for the diagnosis of this condition. PMID- 1890920 TI - [Congenital ventral curvature of the penis]. AB - We report two patients with congenital ventral penile curvature. Both patients were admitted to our Department at 18 years of age, because of deformation which was an obstacle to their normal sexual intercourse. Deformity was corrected with the Nesbit procedure using intraoperative artificial erection. During the surgical procedure no chordee or anomalies of the urethra or spongy tissue could be detected, thus changes were classified in a relatively rare group of deformities due to the inelasticity of tunica albuginea. We have also made some observations on the technique applied which could be helpful in practice. PMID- 1890921 TI - [An increase in plasma digoxin levels after discontinuation of therapy]. AB - In this paper, a course of the disease of a 68-year-old patient treated with medigoxin for congestive heart failure is presented. After being withdrawn from his treatment at the hospital, the patient was administered spironolactone and furosemide. The plasma digoxin level at entry was 1.1 nmol/L, after five days it reached 3.2 nmol/L, and after ten days it was 2.3 nmol/L. The patient had a normal renal function. The interference of spironolactone and its metabolites with the digoxin radioimmunoassay was discussed as a possible explanation for this phenomenon. PMID- 1890922 TI - [Autologous blood transfusion in orthopedic surgery patients]. AB - During a 16-month period, blood for autologous transfusion treatment was taken in 186/788 (23.6%) orthopedic patients. Vasovagal reactions during blood withdrawal were observed in 8.6% of patients. Transfusiologic treatment with autologous blood alone was carried out in 134 (72%) patients. In 36 (19.4%) patients, homologous blood was given in addition to autologous blood. Withdrawal of the required blood unites could not be completed in 33 (17.7%) patients. In this group of patients, the need of homologous blood transfusion was highest (39.3%). In 98.3% of patients, mean values of hemoglobin and hematocrit immediately before the surgical procedure exceeded 100 g/L and 30%, respectively. PMID- 1890923 TI - [Evaluation of the C:A ration in patients with amblyopia treated with penalization methods]. AB - C:A ratios of 50 amblyopes cured by the methods of penalization were examined. Values of C:A ratios were: NC/D = 6.2 +/- 2.01; AC/A = 5.1 +/- 1.81; PC/D = 0.92 +/- +/- 2.03. NC/D and AC/A ratios of amblyopes were higher than the same ratios of the control group of normal children, while PC/D ratios were same for the both groups of subjects. PMID- 1890924 TI - [Child abuse and neglect. II]. AB - In this review, published in two parts, the medical social and legal aspects of child abuse and neglect are assessed. The aim of this paper was to get all the physicians involved in the care of children more thoroughly acquainted with the extent, manifestations and management of abused and or neglected children. The necessity of an organised multidisciplinary approach to this serious medical and social problem iz also stressed. PMID- 1890925 TI - [Cellular immunity and the autoantibody system in polymyositis and dermatomyositis]. AB - Polymyositis and dermatomyositis are clinical forms of inflammatory muscle diseases of unknown etiology. Cellular immunity seems to have great importance in pathogenesis of the idiopathic inflammatory myopathy. It is well known that specifically sensitised lymphocytes from the peripheral blood of patients with polymyositis and dermatomyositis may secrete various mediators (e. g. lymphokines) and be cytotoxic to muscle cell tissue culture as well. In recent years, a variety of anti-muscle antibodies and antibodies to nuclear and cytoplasmic antigens have been identified in the serum of patients with idiopathic inflammatory muscle disease, but their role in this clinical syndrome is still unknown. In this review article authors bring out some of the current state of knowledge about polymyositis and dermatomyositis related autoantibody systems, including biochemical characteristics of the target antigens, epidemiological and clinical significance, and possible role of these autoantibodies in the development of the disease. PMID- 1890926 TI - Systemic administration of acromelic acid induces selective neuron damage in the rat spinal cord. AB - A single systemic administration of acromelic acid A (ACRO), a novel kainate analogue (kainoid), induces a series of characteristic behavioral changes in association with selective damage of interneurons in the caudal spinal cord in adult rats. When ACRO (5 mg/kg) was systemically administered, rats displayed forced extension of hindlimbs followed by frequent cramps and generalized convulsion. Most rats died during the convulsions without neuropathological change. Two rats developed long-lasting spastic paraparesis which persisted at least 3 months. Neuropathological changes were observed only in the rats with persistent paraparesis, in which neuron damage was identified selectively in small interneurons in the lumbosacral cord. The regional difference between kainate- and ACRO-induced neuron damage suggests the existence of plural kinds of kainate receptor subtypes. PMID- 1890927 TI - Organic anion transport study in mutant rats with autosomal recessive conjugated hyperbilirubinemia. AB - The EHBR is a mutant rat strain with congenital conjugated hyperbilirubinemia bred from a Sprague-Dawley rat. Transport of conjugated bilirubin, indocyanine green, and tetrabromosulfophtalein from liver to bile is severely impaired in these rats. Serum bilirubin amounts to 6.0 +/- 0.05 mg/dl (n = 4) in adult rats, with 97% conjugates. The bile flow is reduced to about 65% of the control group, whereas total bile acid in 10-min bile samples is similar. Liver histology of 10 week-old rats revealed neither intracellular pigmentation nor architectural abnormalities. PMID- 1890928 TI - The electrophysiological actions of neurotensin in the central nervous system. AB - The endogenous neuropeptide, neurotensin (NT) alters the firing frequencies of certain neurons in the central nervous system (CNS). This is one of the findings that support the hypothesis that NT is a neurotransmitter substance. The direct application of NT on CNS neurons causes predominantly excitatory effects. These effects occur in a dose-related fashion via a calcium-dependent postsynaptic mechanism. The C-terminal hexapeptide fragment, NT 8-13 exerts similar electrophysiological effects to NT, while the N-terminal octapeptide fragment, NT 1-8 is devoid of such activity. NT produces a significant increase in the firing rates of individual neurons in the substantia nigra (SN), ventral tegmental area (VTA), medial prefrontal cortex (MPF), hypothalamus, and periaqueductal grey (PAG). This excitation occurs with a rapid onset and is readily reversible after cessation of NT application. In contrast, NT has no effect or weak inhibitory effects on the firing rates of neurons in the locus coeruleus (LC) and cerebellum. These electrophysiological actions of NT appear to be unique and not shared by other neurotransmitter and neuropeptide receptor antagonists and agonists that have been studied via direct co-application. NT attenuates dopamine (DA)-induced inhibition associated with direct application onto neurons in the SN and VTA both in vivo and in vitro. Intracellular recordings suggest that direct application of higher concentrations of NT appears to produce 'depolarization block' on individual neurons in the SN, VTA, MPF, and hypothalamus. The electrophysiological consequences of NT application not only show similarities to clinically efficacious antipsychotic medications, but also demonstrate the ability of NT to modulate the activity of dopamine (DA) neurons at the cellular level via specific NT binding sites. These findings further underscore the possibility that NT may play a pre-eminent role in the pathogenesis of, and psychopharmacological management of neurological and psychiatric disorders purportedly related to perturbation of CNS DA systems including schizophrenia. PMID- 1890929 TI - DEMPAQ: Development and Evaluation of Methods to Promote Ambulatory Care Quality. PMID- 1890930 TI - Evaluation of patients with liver tumors for resectability. PMID- 1890931 TI - Diabetes education. PMID- 1890933 TI - [A formal description of the technology for work with the radiation sources in interstitial gamma therapy]. AB - A concept of a radiation technological system with a moving radiation source was proposed. A formal description of technological operations and a technological process was given. An algorithm of the technological process was considered using as an example the organization of work with closed radioactive agents in the radiosurgery department at the Moscow Research Roentgenoradiological Institute. PMID- 1890932 TI - [Radionuclide studies on the hormonal manifestations of heat stress in cancer patients under controlled total hyperthermia]. AB - The results of the investigations of ACTH, HGH, hydrocortisone, glucagon, C peptide, insulin in 180 patients with advanced and metastatic melanomas, soft tissue sarcomas, lung cancers and renal cell carcinomas testify to the development of the syndrome of endocrine hyperfunction in patients under whole body guided hyperthermia as well as of functional pancreas insufficiency. The data presented form a biochemical basis for working out measures to optimally carry out whole-body hyperthermia treatment, aimed at increasing the range of indications for its use in clinical oncology. PMID- 1890934 TI - [Purified sulfur as an agent to relieve the side effects in the radiation therapy of cervical cancer]. AB - The theoretical basis of this work is the development of autosensitization in exposure to ionizing radiation and well-known desensitizing action of sulphuric agents. To reduce clinical manifestations of a reaction to combined radiotherapy 34 women with diagnosis of cervical cancer (stages I and II) were given 0.5-1 g of purified sulphur mixed with 0.25 g of glucose in the morning every 2-3 hours before irradiation, per os; 24 patients received placebo (a mixture of egg powder with glucose), in 21 patients no protective means were used. All 79 patients were given unified adjuvant therapy (polyvitamins, leukogens, folic acid) and diet No 15. A significant decrease in the reaction to therapeutic irradiation was noted in the study group. No side-effects were observed. PMID- 1890935 TI - [The quantitative x-ray assessment of dynamic pathological processes]. AB - Two quantitative criteria of assessment of change in tissue density resulting from developing pathology or its therapy were proposed on the basis of densitometric investigations of longitudinal tomograms. These criteria are differential and integral indicators of density change. The first one characterizes change of optical density of blackening of a tomogram at the point, and the second one--along the line of densitometric scanning--can characterize the state of a part or a whole organ in a studied direction. PMID- 1890937 TI - [The results and tasks of clinical research in radiation neurology]. AB - The paper is devoted to the main stages of development of radiation clinical neurology, paying attention to the contribution of Soviet clinicians in the problem. Neurological disorders in ARS of various degrees of severity at different periods of disease as well as during irradiation at doses, not causing ARS development were described. The importance of clinicophysiological investigations for assessment of CNS function during the development of disease and its aftereffects was shown. The role of psychological investigations and studies on mental abilities of persons, exposed to acute ionizing radiation, was emphasized. PMID- 1890938 TI - [The hematological effects in those exposed to radiation in the accident at the Chernobyl Atomic Electric Power Station]. AB - The paper is concerned with analysis of the data on a picture of the blood of 115 patients with acute radiation syndrome. Basing on the literature data, the authors discuss a possibility of developing leukemia in these patients and in persons, irradiated at lower doses, as a result of radiation affection of hemopoiesis. PMID- 1890939 TI - [The structure of the causes of death following substantial occupational chronic total-body gamma irradiation]. AB - The paper is concerned with analysis of all lethal outcomes in a followed-up group of patients with chronic radiation sickness (931 patients) from external occupational gamma irradiation. In a majority of cases over a 2-2.5 year period a mean dose of total irradiation was 3.26 +/- 0.13 Gy. During a follow-up period of 37 years 177 patients died. Only 2 patients (2.2%) died of chronic radiation sickness resulting from anaplastic anemia. In the first decade (1952-1961) malignant neoplasia, including leukemia accounted for 42.2%; in the second decade the rate for leukemia was 26.2 decreasing to 5.2%; the rates for tumors were 18.4, 20.6, 23.5%, those for CHD were 7.7-41.8%. Despite high doses of irradiation the tumor mortality rate was 22.6%, coinciding with that in industrial countries (15-23%). PMID- 1890936 TI - [Combined digital subtraction angiography and cholangiography in assessing the spread of the tumor process in pancreatobiliary cancer]. AB - The paper is concerned with comparative assessment of the efficacy of digital subtraction angiography and routine angiography in assessing tumor spreading in pancreatobiliary cancer. A combined method of digital subtraction angiography and cholangiography was developed and performed in 41 patients with pancreatobiliary cancer permitting maximum information on the topical location and spreading of a tumor process. The clinical importance of the obtained results permitted recommending simultaneous digital subtraction angiography and cholangiography in patients with hepatobiliary cancer. PMID- 1890940 TI - [The combined (polychemical and radiation) and drug treatment of lymphogranulomatosis patients with generalized lung involvement (stage IV)]. AB - The paper is concerned with analysis of the peculiarities of a course of disease and effectiveness of different therapeutic programs in 121 primary patients suffering from Hodgkin's disease with generalized lung lesion (true stage IV). The 5-year total and recurrence-free survival of patients after polychemoradiotherapy was 59.5 and 45.6%, respectively. Prognosis of disease in patient with generalized lung lesion is determined mainly by the development of a specific process in pulmonary tissue and, to a lesser degree, by spreading of disease via the lymphatic collectors. The authors have shown the appropriateness of combined therapy of this group of patients. Therapy includes cycles of polychemotherapy for achieving remission and radiotherapy including total irradiation of the affected lung for its consolidation. PMID- 1890941 TI - [Perfusion scintigraphy in the diagnosis of lung hypoplasia in children]. AB - Perfusion scintigraphy was used as a method of screening in children with prolonged and persistent chronic nonspecific pulmonary diseases with an obscure x ray picture of diagnosis of lung hypoplasia. Its scintigraphic sings (considerable reduction of the capillary flow by 50%; a unilateral lesion; a clear locality of a pathological zone on a scintigram, corresponding by its volume to a lobe or the whole lung; relative uniformity of residual perfusion in the affected lobe) were detected in 21 patients. The results of scintigraphy were also used as an objective indicator for bronchopulmonary investigations and angiopulmonography. PMID- 1890942 TI - [The depth distribution of neutron-capture events in 10B nuclei during the irradiation of a water phantom with neutrons from the channels of the BR-10 reactor]. AB - The authors present the results of experimental investigations of distribution of capture events on nuclei 10B by the depth of a water phantom during its irradiation with beams T-4 and B-3 of the BR-10 reactor. A ferrous sulfate dosimeter with added boric acid was used as a detector of such events. The depth of a water phantom on which the effect of boron capture by a neutron beam is decreased 2-fold, is 1.7 cm. For the B-3 beam a curve of depth correlation of neutron capture events had a broad maximum at a depth of 4-5 cm. PMID- 1890943 TI - [Phantom research in the individual dosimetric planning of the intracavity irradiation of uterine cancer patients]. AB - The paper is concerned with the results of dose measurements on a uterine phantom under the conditions close to those of the practice of radiotherapy of endometrial cancer patients using the AGAT-B unit. Comparison of experimental and rated dose values made it possible to find points of particular clinical alertness as well as a point of the control of accuracy of dose formation during a radiotherapeutic session. PMID- 1890944 TI - [A computer system for planning radiation therapy--the ROPLAN]. AB - A computerized system of optimum plans of radiotherapy (computer SM 1420) was developed for the first time in the USSR. The ROPLAN system was adapted to a dosimetric design of irradiation sessions for all radiotherapy units, manufactured in the USSR, and provides for modes of initialization, design, storage and collection of data for all radiotherapeutic methods. PMID- 1890945 TI - [The suspicion of a pancreatic tumor]. PMID- 1890947 TI - [The radiation loads on the red bone marrow and gonads during x-ray diagnostic examinations of newborn infants based on the results of radiation dosimetry in the trabecular bone tissue]. PMID- 1890946 TI - [Neurotropin: the different aspects of its action and clinical use]. PMID- 1890948 TI - [The thermoradiotherapy of malignant salivary gland tumors]. AB - The paper is devoted to the discussion of problems of the effectiveness of thermoradio- and radiotherapy of patients with locally advanced malignant tumors of the salivary glands. The 1st group of 14 patients received gamma-beam therapy, and the 2nd group of 32 patients was given radiotherapy combined with local microwave hyperthermia. After delivering a dose of 40 Gy a decrease of a tumor size by greater than 50% was noted in 50% of the patients of the 1st group and in 76% of the patients of the 2nd group. Thermoradiotherapy prove to be most effective in patients with adenoid cystic carcinoma, tumor regression over 75% was noted in half of them. Complications in thermoradiotherapy were unnoticed. PMID- 1890949 TI - Detection of toxic viral-associated double-stranded RNA (dsRNA) in influenza infected lung. AB - While many of the molecular events in viral replication are well studied, the molecular mechanisms by which viral infections trigger such constitutional symptoms as fever and 'malaise' are unknown. The hypothesis that these viral constitutional symptoms can be triggered by the toxic action of dsRNA associated with viral replication was investigated. Total lung RNA from mice acutely infected with PR8 influenza virus, but not from sham-infected mice, was shown to induce fever and altered sleep (excess slow-wave sleep, enhanced amplitudes of electroencephalographic slow waves, and reduced rapid eye movement sleep) when injected into the rabbit brain. Viral-associated dsRNA was shown to be responsible for the rabbit responses by differential nuclease digestion. Influenza viral dsRNA was directly demonstrated in the active lung RNA preparations by reverse transcriptase-polymerase chain reaction techniques. The time course of the responses paralleled those seen in the same model inoculated with nanogram quantities of the synthetic dsRNA polyriboinosinic polyribocytidylic acid and suggested that they were mediated by induced cytokines. A model for the role of viral-associated dsRNA in eliciting both local cytotoxicity and viral constitutional symptoms is presented. PMID- 1890950 TI - Comparison of the human immune response to live oral, killed oral or killed parenteral Salmonella typhi TY21A vaccines. AB - The live oral typhoid vaccine Ty21a has proved to confer protection against the disease at least as effectively as killed parenteral vaccines, whereas killed oral vaccines have not been protective in field trials. This prompted us to compare the immune response of subjects vaccinated either with live oral, killed oral or killed parenteral Salmonella typhi Ty21a vaccine. The immune responses were studied by analysis of peripheral blood antibody-secreting cells (ASC), believed to reflect the mucosal immune response. Live and killed bacteria administered by the oral route elicited immune responses of similar specificity and Ig class profile (IgA dominating), but the response to the live vaccine was significantly stronger and lasted longer. The administration route, on the other hand, influenced the antigenic specificity of the ASC response suggesting different processing of the antigen by the systemic and local immune systems. Thus, the response after oral vaccination was almost exclusively directed to the surface O-antigen, whereas after parenteral vaccination an equally strong response was seen to the O-antigen, to lipopolysaccharide core and to flagella. PMID- 1890951 TI - Characterization of Borrelia burgdorferi invasion of cultured endothelial cells. AB - Borrelia burgdorferi can adhere to cultured endothelial cells and penetrate through cell monolayers by passing through intercellular tight junctions and through the host cell cytoplasm. Borrelia burgdorferi strains which were isolated from different sources and areas of the U.S. all demonstrated similar invasive capabilities. Bacterial penetration from the apical to the basal surface of the monolayer was 20 times more efficient than from the basal to the apical surface. Borreliae which were non-viable as a result of either heat treatment or ultraviolet (UV) irradiation showed reduced association with the endothelial cell monolayer and loss of invasive capabilities. Borreliae were able to invade when protein synthesis was inhibited with streptomycin or chloramphenicol. When assays were conducted at 4 degrees C, bacterial penetration of the monolayer was completely inhibited. Treatment of borreliae with proteases affecting outer surface proteins greatly reduced cell association and bacterial invasion. PMID- 1890952 TI - Immunity conferred by Aro- Salmonella live vaccines. AB - The specificity of protection conferred by Aro- salmonellae was studied in BALB/c mice challenged 3 months after intravenous (i.v.) vaccination, more than 1 month after the vaccine had been cleared. Oral challenge showed better protection than i.v. challenge. Salmonella typhimurium aroA SL3261 conferred very good protection against wild-type S. typhimurium C5 (over 10,000 x LD50). Cross protection experiments were performed using S. typhimurium, S. enteritidis and S. dublin for vaccination and challenge, including variants of S. typhimurium and S. enteritidis of similar virulence differing in the main LPS antigen (O-4 or O-9). Salmonella typhimurium aroA conferred solid protection against S. typhimurium (O 4), but no protection against wild-type S. enteritidis (O-9). However challenge with LPS variant strains showed that although protection was generally better to strains of the homologous LPS type, specificity of protection was determined more by the parent strain background (S. typhimurium or S. enteritidis) of the challenge than by O-factors 4 or 9, suggesting that other antigens are involved. The nature of the protective antigen(s) in this model is unclear, but it does not appear to be the main O-specific antigen. A S. enteritidis Se795 aroA vaccine gave good protection against wild-type S. enteritidis Se795 2 weeks after vaccination, but much less at 3 months (approximately 10-200 x LD50), although the persistence of the S. enteritidis aroA vaccine in the liver and spleen was similar to that of the S. typhimurium vaccine, and the wild-type Se795 challenge strain was of similar virulence to S. typhimurium C5. A S. dublin aroA vaccine conferred similar protection against wild-type S. dublin (approximately 300 x LD50). PMID- 1890954 TI - The low-Ca2+ response virulence regulon of human-pathogenic Yersiniae. AB - The Lcr is thought to function when the yersiniae infect their mammalian host (see Fig. 2). At present, all evidence points to roles of the Lcr in protecting the bacteria in extracellular niches. We can speculate that early in infection, the yersiniae experience a 37 degrees C extracellular, Ca(2+)-containing environment. Temperature-induction and down-modulation by Ca2+ would occur for Lcr genes, resulting in a cytotoxic and weakly anti-phagocytic surface on the bacteria. Yersiniae that are taken up into macrophages may find a low-Ca2+, inductive environment for expression and release of Yops and V antigen. Upon release from macrophages, the accumulated Yops may render the bacteria sufficiently anti-phagocytic to resist ingestion by neutrophils, and Lcr virulence proteins such as YopM, and perhaps V antigen and other Yops might act to dampen the inflammatory response and prevent secondary influxes of phagocytes. The abundant nucleotides from necrotic host cells undergoing nucleic acid breakdown might then promote extracellular growth. Even though Lcr virulence genes would be expressed at an intermediate level under these conditions, this may be sufficient for the continued undermining of the host natural defenses. It also is possible that there are additional environmental signals, not yet identified, that modulate Lcr virulence gene expression and permit strong expression in extracellular microenvironments that arise as a result of the host yersiniae interactions. PMID- 1890953 TI - Characterization of thermostable direct hemolysins encoded by four representative tdh genes of Vibrio parahaemolyticus. AB - Four tdh genes encoding thermostable direct hemolysin (TDH) cloned from two representative strains of V. parahaemolyticus (tdh 1 and tdh 2 from a hemolytic strain, tdh3 and tdh4 from a non-hemolytic strain) have different nucleotide sequences (the maximum divergence: 3.3%). In this study, each tdh gene product was purified from the lysate of Escherichia coli cells carrying the cloned gene and their properties were compared to investigate the influence of the amino acid substitutions caused by these base changes. The four tdh gene products showed different electrophoretic mobilities under non-denaturing conditions. All the gene products had hemolytic activities for various animal erythrocytes, stimulated vascular permeability in the rabbit skin, and were lethal to mice, although their potencies were slightly different. Antigenicities of the four gene products were indistinguishable. These results indicate that the four tdh genes have evolved to maintain a fundamental molecular structure and biological activities of the gene products and minor structural and/or charge differences of the molecules are perhaps responsible for the slight divergence of their biological activities. PMID- 1890955 TI - Against medical ethics: a philosopher's view. PMID- 1890957 TI - Performance of medical students in case-based and essay components of written anatomy examinations. AB - This paper reports on second-year medical students' performance in the case-based and traditional essay components of the gross anatomy written examinations at the University of Otago held at the end of 1988 and 1989. The mean marks for these two components of the examinations are presented for the three main categories of student entry. Differential performance on the case-based component relative to the essay component has been determined for each student in the class and ranked in order. The proportions of students in the three entry categories falling in the various quartiles for the class are given. The data show that when an intensive programme of case-based learning was followed, as in 1988, all three categories performed similarly on the case-based component relative to the essay component. When a less intensive programme of case-based learning was used, as in 1989, the differential performance of the preferential undergraduate and graduate categories was different to each other. The findings suggest that the achievement of students in the case-based projects is dependent upon the organization of the programme and the extent to which students and staff become involved in the projects. The writing of reports on the cases by students for assessment in 1988 may have had an important influence on the outcome for this year. PMID- 1890956 TI - Presidential mission to Africa. PMID- 1890958 TI - Reliability and validity of the objective structured clinical examination in paediatrics. AB - The assessment of clinical competence has traditionally been carried out through standard evaluations such as multiple choice question and bedside oral examinations. The attributes which constitute clinical competence are multidimensional, and we have modified the objective structured clinical examination (OSCE) to measure these various competencies. We have evaluated the validity and reliability of the OSCE in a paediatric clinical clerkship. We divided the examination into the four components of competence (clinical skills, problem-solving, knowledge, and patient management) and evaluated the performance of 77 fourth-year medical students. The skill and content domains of the OSCE were carefully defined, agreed upon, sampled and reproduced. This qualitative evaluation of the examination was both adequate and appropriate. We achieved both acceptable interstation and intertask reliability. When correlated with concurrent methods of evaluation we found the OSCE to be an accurate measure of paediatric knowledge and patient management skills. The OSCE did not correlate, however, with traditional measures of clinical skills including history-taking and physical examination. Our OSCE, as outlined, offers an objective means of identifying weaknesses and strengths in specific areas of clinical competence and is therefore an important addition to the traditional tools of evaluation. PMID- 1890959 TI - An oral practical examination in emergency clinical surgery. AB - A body of students were asked about their views regarding an oral practical examination in clinical surgery that had been in practice for over 12 years. This is an examination with the planned objective to test problem-solving abilities and professional attitudes in emergency surgery. Verbal emergency simulation aided by appropriate pathological specimens, surgical instruments and X-rays are put forward by the examiners, and the candidate is asked to respond. One hundred and ninety-four students returned their questionnaire out of a total of 196 students (99% response rate). Candidates who were satisfied with their answers in the examination numbered 127 (65%), while 67 candidates were dissatisfied (35%). Reasons for dissatisfaction were cited as difficult and complex emergency simulation questions, expressed by 44 candidates (23%), and anxiety generated by confrontation of the examiners, expressed by 23 candidates (12%). One hundred and thirteen students (58%) thought a change in the format of the examination was not needed, while 47 students (24%) suggested a change mostly towards standardization of the examination. Emergency clinical surgery is an important area of the surgical curriculum that needs to be assessed properly. A more standardized version of this oral practical examination could perhaps provide a useful tool of assessment. PMID- 1890960 TI - Reliability and efficiency of components of clinical competence assessed with five performance-based examinations using standardized patients. AB - The present study was conducted to provide in-depth information on the reliabilities of measures of the separate components of clinical competence (e.g. data collection, test interpretation, diagnosis, etc.) assessed by a performance based examination consisting of standardized-patient cases administered to five classes of senior medical students at Southern Illinois University School of Medicine. In general, the reliabilities of the competencies as they were actually measured on the examination (using the number of cases on which each competency was actually measured) were small, with 54% less than 0.30 and 75% less than 0.40. For generalizability coefficients pooled across the five classes and projected to a common number of k = 10 cases, two of the nine competencies had reliabilities in the 40s, a third was close to 0.40, and the remaining six were in the low 20s. The number of cases needed for the competencies to achieve the recommended reliability of 0.80 ranged from 45 to 170 cases, with six of the nine competencies requiring over 100 cases to reach the 0.80 level. The low reliabilities of these measures of the components of clinical competence raise serious questions about using the scores as indicators of student performance. PMID- 1890961 TI - The teaching of communication skills in United Kingdom medical schools. AB - A survey was carried out of the teaching of communication skills in medical schools in the United Kingdom during the academic year 1989/90. Comparison with previous surveys shows a considerable development over the last 10 years. Departments of psychiatry and general practice continue to play a major part in such teaching. There was wide variation in educational objectives and in the curricular time available. Concern is expressed about the methods of assessment and the degree of integration between departments. Future plans and the perceived barriers are reported and the implications discussed. PMID- 1890962 TI - The lessons of deafness: deafness awareness and communication skills training with medical students. AB - This paper describes a 1-day course on deafness awareness and communication skills with fourth-year medical undergraduates and summarizes their evaluation of the course. Deaf people commonly experience major communication difficulties with doctors. This course gives students an awareness of deafness (and of the insights deaf people can give to an understanding of communication)--the lessons of deafness--and challenges some critical assumptions in medical practice. Students are given personal experience of deafness and of the consequent powerlessness and loss of self-confidence, while also learning new communication skills which they then apply in a role-play consultation with a deaf patient. Systematic evaluation has been built into the programme and student opinion has been unanimously enthusiastic. PMID- 1890963 TI - Training medical practitioners in information transfer skills: the new challenge. AB - Traditionally, undergraduate medical education has concentrated on teaching students how to gather information or take medical histories from their patients. However, research increasingly indicates that there is a need for medical practitioners to improve their skills in information transfer in a way which will increase the probability that patients are active collaborators in their treatment. Consequently, Newcastle Medical School has sought to develop training packages for medical students in information transfer skills. This paper describes the resulting training programme with particular emphasis on the areas selected for training, the methods by which students are taught, the necessary interactional skills and the assessment procedures which are applied. PMID- 1890964 TI - Independent learning: an exploration of student grand rounds. AB - Grand rounds (GRs) for students were started with the 1987 cohort of first-year clinical students at two University of Toronto teaching hospitals. A qualitative exploratory evaluation, using questionnaires, interviews and observation, of a sample of 78 staff and student participants showed that the aim of the GRs to activate student skills in independent study was achieved but that interaction between students and other clinical and laboratory specialists as a basis for round presentation was less than intended. Students spent an average of 10 hours on independent work. Round presentations were of a high standard. Students' main concerns were the amount of freedom and feedback given. The goals of the programme as perceived by students influenced both the work done and the style of presentation. These outcomes were contrasted with a UK qualitative study of student presentations on ward rounds, and the importance of an appropriate context for independent work highlighted. PMID- 1890966 TI - IDEA: an index of dental educational activity. AB - This paper reports on the construction of an index of dental educational activities (IDEA) developed as part of an exploration of continuing professional development activities among a sample of general dental practitioners (GDPs) in the Yorkshire Region in Britain. To assist in the interpretation of the index scores an analogy is drawn to an academic examination. Only 50% of the GDPs passed, 31% achieving scores of 40% or less and 9% distinctions. Higher IDEAS were achieved by practitioners who spent a lot on their dental education, those who intended to attend continuing education events next year practice principals, those who worked in larger practices and men GDPs. Little difference in the scores was observed by the age of the practitioner, experience of working in hospital or distance from the central continuing education centre. Discussion centres on the utility of the index as a summary of updating practices and its potential as a comparative measure across health professions. High levels of continuing professional development and thus high IDEAs must be encouraged, but they need to be accompanied by high quality care and effective job performance. PMID- 1890965 TI - An assessment of academic performance and personality. AB - This study examines whether personality profiles, using personality factors, or clusters of personality factors, are associated with academic success. One hundred and forty medical students of the University of Wales College of Medicine were invited to complete a personality questionnaire (Cattell 16 PF) as they sat their final examinations in June 1988. A total of 129 usable forms were obtained. The students were divided into four groups dependent on their academic performance, which had been monitored throughout the course. The majority (62%) had no academic problems, but 16 (12%) students had serious difficulties, which entailed delaying qualification by at least 6 months. There was no relationship between the scores obtained for the students' first attempt at A-level and their subsequent medical school academic performance. However, students who obtained a degree either before or during their medical course were significantly less likely to have academic problems. Academic success was not associated with any of Cattell's personality factors. This was true of previously reported groups of factors associated with the poor student performance, and regardless of first or second order factors. We conclude that this personality profile is unlikely to be helpful in selecting future intakes of medical students, although a prospective study would be required for a definite answer to this question. PMID- 1890967 TI - Exercise as prevention: do the health benefits derive in part from lower iron levels? AB - The mechanism by which exercise, a key component of modern preventative medicine, protects man from strikingly different diseases such as heart disease and cancer, is largely a mystery. It is proposed that exercise-induced reductions in iron levels, either through iron loss or enhanced iron storage, could be responsible for some of the beneficial effects. Possible roles for iron in coronary artery disease and cancer have recently emerged, particularly as a catalyst for oxygen free radical-induced tissue damage. The iron hypothesis is consistent with the graded reductions in mortality observed as a function of fitness level, and it is the first unified mechanism which can explain the reductions in both heart disease and cancer. If confirmed, preventative medicine in the future will need to include close monitoring of iron levels and, possibly, occasional blood donation for those with moderately high iron stores. PMID- 1890968 TI - A novel hypothesis concerning the mechanisms of activation, and of control, of periodontal bone loss. AB - Chronic inflammatory periodontitis fulfills the classical definition of an infectious disease in that it is a disease of the host caused by the activities of one or more parasites. Typically, the etiology of an infectious disease has been defined as the specific microbe which incites the disease process, even though the quality and nature of host responses to the pathogen may underlie much of the pathology seen. This approach in the study of the etiology of chronic periodontitis has not resulted in the identification of a single 'periodontopathogen', but rather is leading to the realization that multiple sets of microbes may induce the same endpoint, albeit some possibly more efficiently than others. The premise of this paper is that a different view of the literature in the area, with the primary emphasis on the mechanisms of damage and resistance to periodontitis, reveals a probable commonality, rather than a plethora of diseases. The concept of a mechanism-based etiology, rather than of a microbe based one, deserves consideration for this complex, host-parasite interaction. The novel hypothesis presented here is that the common virulence factor of chronic periodontitis is lipopolysaccharide (LPS), that the central damaging mediator is a cyclooxygenase product of arachidonic acid (probably prostaglandin E2), and that the critical resistance mechanism that limits disease activity is the effective, peripheral neutralization of LPS by emigrated polymorphonuclear neutrophils. PMID- 1890969 TI - Somatization disorder and the chronic candidiasis syndrome: a possible overlap. AB - The close similarity between the complex of symptoms found in the recently described Chronic Candidiasis Syndrome and the Somatization Disorder is pointed out. Some evidence in support of the validity of the Chronic Candidiasis Syndrome is presented including some studies from the past and more recent medical literature regarding symptoms, physiological effects, and immunological findings accompanying Candida infections. Logical possibilities for the relationship of each disorder with the other is discussed. It is concluded that there is a possible overlap of the two disorders and that some patients currently diagnosed with Somatization Disorder may respond to the treatment for Chronic Candidiasis. PMID- 1890970 TI - The big bang and its universal hernias. A sire of pathologies. AB - The 'Big Bang' is used to describe the origin of the Universe. While such an event could not create itself the expression is graphic. Tissue damage, traumatic, thermal, chemical; bites; insect, animal or human are all bad, but also well known factors which favor and initiate pathogenic activity. Antedating and outranking all those is the inherent tendency of the universal contractile chamber to rupture and spill its contents, especially when mural labors encounter sphincteric intransigence. This is a newer concept of pathology more basic than infection, allergy, cancer, trauma, etc. The phenomenon is also an important part of the mechanisms whereby those unessential factors pathologize making various kinds of 'itis'. The mammalian body is composed of contractile tubes and bags. So one might call their universal inherent tendency to herniate, i.e., to burst and leak, the Father of pathologies, but the Big Bang seems more descriptive. PMID- 1890971 TI - A metal-linked gapped zipper model is proposed for the 90 kDa heat shock protein estrogen receptor interface. AB - A novel arrangement is proposed for the association of the 90 kDa heat shock protein (hsp 90) dimer and the human estrogen receptor (hER) monomer. Secondary structure analyses of the hsp 90 molecule reveal the presence of a cysteine containing, leucine-rich, heptad repeat, which we refer to as region C. Similar analyses on the hER, at its hormone binding domain (HBD), have indicated the presence of a central subdomain bordered by 2 alpha-helical flanking segments which also display the heptad substructure. Due to its predicted potential for conformational change (1) we refer to this central subdomain as the Helix Conversion Unit or HCU. It contains an HX5C peptide and shares significant homology with the metal-binding domain of a gag-encoded HIV-LAV protein (2). We predict that, by virtue of its presence in duplicate, region C may be capable of simultaneous leucine zipper-like pairing with the hER at its flanking helices, as well as the formation of a shared CCHC-box-type metal binding link with the same hER at the putative HCU which lies in between. PMID- 1890972 TI - Dementia in cancer patients undergoing chemotherapy: implication of free radical injury and relevance to Alzheimer disease. AB - A number of neurological disorders including Alzheimer and Parkinson disease have been suggested to be caused by processes leading to lipid peroxidation. Other theories implicate the accumulation of damaged DNA, resulting from a defect in DNA repair, in the pathogenesis of these disorders. I suggest that these theories might be related, since the hydroxy free radical is known to attack DNA and inactivate enzymes so that oxygen metabolism has the potential to interfere with the maintenance of genomic integrity. Since psychometric intelligence correlates highly with erythrocyte glutathione peroxidase activity, a free radical scavenger, perhaps this might explain the marked intellectual impairment caused by chemotherapeutic agents such as cytosine arabinoside, as well as in Alzheimer disease. PMID- 1890973 TI - Visual perception--a hypothesis. AB - Based on the results of after-image experiments, it can be concluded that the retinal perception of image position is linked to head position information, since this affects after-image positioning. Why actual perception of object position is not affected is hypothesised as a resetting of the retinal horizon, from information received on head position. Tilting of the after-image is thus explained as superimposition of the former image on a reset (tilted) horizon (axis). PMID- 1890974 TI - Recirculation of cerebrospinal fluid through the tela choroidae is why high levels of melatonin can be found in the lateral ventricles. AB - Evidence is presented to support the hypothesis that cerebrospinal fluid (CSF) is transported through the tela choroidae and recirculated in the ventricular system. The concept that the CSF is resorbed by the arachnoid villus-superior sagittal sinus system is accepted as fact. The experimental studies on which the currently accepted theory is based were published in 1914 by Dr Lewis Weed. Weed used a low pressure (near physiologic) method and a high pressure (non physiologic) method. His observations with the high pressure method are a basis for the theory of arachnoid villus absorption. On the other hand, his low pressure method provides evidence that CSF is absorbed in the area of the basilar cisternae. Studies of communicating hydrocephalus and chemical analysis of ventricular melatonin give evidence that CSF recirculates through the tela choroidae back into the ventricles. PMID- 1890975 TI - Immunomodulation of the mother during pregnancy. AB - The concept that the immune responsiveness of the mother is reduced during pregnancy arose from studies which appeared to show that immune response to certain antigens is reduced during pregnancy (1, 2). Various substances claimed to have immunosuppressive or immunomodulating effect include alpha fetoprotein, placental proteins, early pregnancy factor (EPF), human chorionic gonadotropin (HCG), corticosteroids, estrogens, androgens and progesterone (2). To summarise a body of literature, there is very little change in the immune competence of the mother during pregnancy. This makes sense, as generalized immunosuppression would be a risky way to ensure the survival of the fetus. Immune enhancement and subsequent immunomodulation of the mother is likely to be the mechanism operative during pregnancy. It is conceivable that the overall immune response in pregnancy could be the net result of an interplay of various interactions that may be operating to ensure non-rejection of the antigenically alien fetus while at the same time preventing a state of excessive immunosuppression. Such a dynamic homeostatic mechanism appears to be important for the successful completion of pregnancy. PMID- 1890976 TI - Energy reactions in atherosclerosis: the implication of tricarboxylates in the pathogenesis of the disease. AB - Acetyl CoA is the origin of steroid synthesis and the carbon atoms of the acetate provide the molecular basis for all endogenous cholesterol. Citrate, by virtue of its feedback to acetyl CoA in decreased metabolic respiration, may influence steroid synthesis as it does lipogenesis. It is therefore conceivable that endogenous and possibly exogenous citrates may be important in regulating cholesterol synthesis and its pathological consequence, vascular occlusion. PMID- 1890977 TI - To wall off neoplasms with more viscous extracellular matrix. AB - Normal inflammatory and immune mechanisms would destroy most neoplasms if the neoplasm did not alter its immediate environment to weaken the host defenses. Based on factors that seem to increase extracellular matrix viscosity, methods of enhancing host resistance in the vicinity of the tumor are suggested by the author. This includes adjuvant therapy, pyridoxine antagonist, cytokines, beta carotene, retinoids, vitamin C, iodides, bromides, and pellagragenic substances. Hyperthermia may also have an effect. PMID- 1890978 TI - A biological hypothesis for the FAB classification of acute myeloid leukaemias. AB - A biological hypothesis which is based upon the response of AML blast cells to retinoic acid alone and in combinations with other differentiating agents in primary culture, is proposed for the FAB classification of Acute Myeloid Leukaemias. The present biological hypothesis accounts for the biological and clinical observations in AML. PMID- 1890980 TI - Cardiac parasympathetic innervation in Chagas' heart disease. AB - Trypanosoma cruzi is thought to selectively destroy the postganglionic cardiac vagal neurons of chagasic cardiac patients. This theory is based on morphologic and functional evidences obtained from chagasic individuals who were in very advanced stages of the disease. We have studied chagasic patients who were in both the early and late stages of the disease. Our findings and the review of the available literature suggest that myocardial damage and mild left ventricular dilatation precede the cardiac parasympathetic abnormalities. Furthermore, we have found a strong correlation between the degree of left ventricular dilatation and the extent of cardiac parasympathetic impairment. Consequently, we propose that the cardiac parasympathetic abnormalities arise as a compensating mechanism for the progressive left ventricular dilatation. PMID- 1890979 TI - Can protracted relapsing fever resemble Lyme disease? AB - We report the case of a Protestant missionary who contracted tick-borne relapsing fever in 1979 while serving in the Sudan. Despite tetracycline treatment, his acute illness ran a protracted course, with migratory polyarthralgias lasting approximately 10 months. Symptoms recurred in 1984 and have persisted. At regular intervals, the patient has experienced recurrent episodes of fever, generalized fatigue, bilateral upper and lower extremity muscle weakness, and asymetric large joint polyarthralgia. Indirect fluorescent antibody testing of sera demonstrated titers of 1:16 for B. burgdorferi and 1:64 for B. hermsii, and immunoblotting confirmed past exposure to relapsing fever, but not Lyme disease. It is hypothesized that this individual's chronic symptoms have been related to relapsing fever, and that in certain situations or in select individuals, relapsing fever can be capable of producing a chronic clinical picture analogous to Lyme disease. PMID- 1890982 TI - Large-vessel occlusion in sickle cell disease: pathogenesis, clinical consequences, and therapeutic implications. AB - Much of the morbidity and mortality in sickle cell disease (SCD) is caused by tissue ischemia and infarction resulting from vascular occlusion. Research in this area has been dominated by the hypothesis that vascular occlusion in SCD is due primarily to microvascular obstruction by sickle erythrocytes (SS RBC), yet there is no direct evidence that microvascular occlusion is responsible for any of the vasocclusive complications of SCD. In this paper an alternate hypothesis is proposed: that thrombotic occlusion of larger arteries and veins is an important factor in many of the vasocclusive complications of SCD. Large-vessel cerebral arterial disease (intimal hyperplasia with superimposed thrombosis) has clearly been established as the most important cause of stroke in SCD, and considerable evidence suggests that pulmonary arterial thrombosis/embolism is a major cause of pulmonary infarction and hypertension. The involvement of large vessel thrombosis in painful crisis, aseptic necrosis of bone, priapism, leg ulcers, retinopathy, and miscarriage has not been adequately investigated. Large vessel occlusion in SCD is probably a consequence of the abnormal adhesive and procoagulant properties of SS RBC, which produce endothelial damage, secondary intimal proliferation, and thrombosis. Techniques currently used to treat large vessel occlusion in other disorders (antiplatelet and anticoagulant agents, thrombolytic therapy, angioplasty, endarterectomy, and vascular bypass surgery) should be considered in sickle cell subjects with large-vessel occlusion, especially in the cerebral vasculature. PMID- 1890983 TI - Iron stores and the international variation in mortality from coronary artery disease. AB - Possible roles for iron in coronary artery disease (CAD) have emerged, including contributions to atherogenesis and/or the vulnerability of the myocardium to ischemia/reperfusion events. The value of hepatic storage iron as a potential risk factor for CAD was evaluated independently and in combination with various lipoprotein indices using CAD mortality data from 11 countries along with available data on liver iron stores. CAD mortality rates were found to be best correlated with the liver iron-serum cholesterol product in both men (r = 0.72) and, more importantly, in both genders combined (r = 0.74). It was also found that estimated CAD incidence could be related in a non-linear fashion to iron cholesterol values in a simple normal distribution model where all subjects above a threshold value of iron-cholesterol were assumed to have CAD. Hepatic iron values thus appear to be useful in describing the differences in CAD due to both diet (and/or culture) and sex. PMID- 1890981 TI - Persorption of raw starch: a cause of senile dementia? AB - Intact starch granules in food can pass through the intestinal wall and enter the circulation. They remain intact if they have not been cooked for long enough in the presence of water. Some of these granules embolise arterioles and capillaries. In most organs the collateral circulation suffices for continued function. In the brain, however, neurones may be lost. Over many decades the neuronal loss could be of clinical importance. To test this hypothesis, there is a need to examine brains for the presence of embolised starch granules. Examining tissues polariscopically clearly distinguishes starch granules from other objects of similar appearance. PMID- 1890984 TI - Tuberculosis outbreak among persons in a residential facility for HIV-infected persons--San Francisco. AB - From December 19, 1990, through April 4, 1991, 12 cases of clinically active pulmonary tuberculosis (TB) were diagnosed at a residential facility for HIV infected persons in San Francisco. This report summarizes results of the outbreak investigation. PMID- 1890985 TI - Homicide followed by suicide--Kentucky, 1985-1990. AB - During March-May 1990, three widely publicized homicides followed by suicides occurred in Kentucky. Because the three incidents shared many features, the Division of Epidemiology, Department for Health Services, Kentucky Cabinet for Human Resources, conducted a study to determine the extent of the problem and the characteristics of perpetrators and homicide victims. This report presents the findings of this study. PMID- 1890986 TI - Current tobacco, alcohol, marijuana, and cocaine use among high school students- United States, 1990. AB - Patterns of tobacco, alcohol, and other drug use usually are established during youth, often persist into adulthood, contribute substantially to the leading causes of mortality and morbidity, and are associated with lower educational achievement and school dropout. This report presents selected data on current use of tobacco, alcohol, marijuana, and cocaine among 9th-12th grade students from two components of the Youth Risk Behavior Surveillance System: 1) the 1990 national school-based Youth Risk Behavior Survey (YRBS) conducted during April May 1990 and 2) similar surveys conducted by departments of education in 22 states and four cities during the same time period. PMID- 1890987 TI - Expression and regulation of the rabbit uteroglobin gene in transgenic mice. AB - The rabbit uteroglobin (UG) gene, with varying lengths of 5' flanking sequence, was introduced into the mouse genome to investigate the DNA sequences required for tissue-specific expression and regulation by steroid hormones. The pattern of expression and steroid hormone regulation of the transgene was compared to the expression and regulation of the endogenous mouse UG-like gene. In the rabbit, UG is induced in the uterus by progesterone and is expressed constitutively in the lungs, where it is weakly regulated by glucocorticoids. Genomic DNA fragments containing the complete UG-coding sequence with 4.0 (UG4.0), 3.0 (UG3.0), 2.3 (UG2.3), or 0.6 (UG0.6) kilobases of 5' flanking sequence were used to establish lines of transgenic mice. Expression of UG mRNA was observed in the lungs of UG4.0 (2/4 lines), UG3.0 (4/4 lines), UG2.3 (1/2 lines), and UG0.6 (4/4 lines) mice. Uterine expression was observed in UG3.0 (3/4 lines), UG2.3 (1/2 lines), and UG0.6 (2/4 lines). In the lungs of UG3.0 and UG2.3 mice, RNA expression was stimulated by treatment with dexamethasone. In the one line of UG3.0 mice examined, UG was regulated by ovarian steroids in the uterus. The endogenous mouse UG-like gene showed the major site of expression to be in the lung. Unlike the transgene, the endogenous gene was more strongly stimulated by glucocorticoids. Thus, we conclude that the cis elements needed for pulmonary expression of UG are contained within the UG2.3 fragment used to generate transgenic mice, but that other elements are required for full glucocorticoid regulation. Also, the transgene did not show the full uterine expression observed in the rabbit, but regulation by the ovarian steroids was observed. PMID- 1890988 TI - Heterogeneity of expression and secretion of native and mutant [AspB10]insulin in AtT20 cells. AB - AtT20 (pituitary corticotroph) cells were transfected with either the native or a mutant [AspB10]rat insulin II gene, using a plasmid containing the insulin gene and a neomycin resistance gene under the control of independent constitutive promoters. The cellular immunoreactive insulin (IRI) content ranged from 0.8-440 ng/10(6) cells, with the highest value similar to that found for a rat insulinoma cell line (RIN) and corresponding to approximately 1% that of native pancreatic B cells. There was a direct correlation between insulin mRNA levels and IRI content and no correlation between mRNA levels and rat insulin II gene copy number. Furthermore, in some lines the insulin II transgene was lost even though the gene encoding neomycin resistance was retained. IRI release was stimulated up to 4 fold by isobutylmethylxanthine in all lines transfected with the native rat insulin II gene, and HPLC analysis showed most IRI as fully processed insulin, with less than 5% as proinsulin. These cells, thus, directed most proinsulin to secretory granules for conversion and regulated release regardless of the absolute amount of IRI expressed. One of the lines transfected with the AspB10 mutant gene (line AA9) released nearly 50% of IRI as proinsulin under basal conditions, with stimulation of insulin, but not proinsulin, release by isobutylmethylxanthine. This confirmed our previous finding of partial diversion of this mutant proinsulin from the regulated to the constitutive pathway. A second line (IC6) expressing the same mutant gene at much higher levels appeared to direct all mutant proinsulin to the regulated pathway, suggesting that for this particular mutant proinsulin, the secretory pathway employed by the transfected cells can be affected by the amount of proinsulin synthesized. PMID- 1890989 TI - Hormonal regulation of vitellogenin genes: an estrogen-responsive element in the Xenopus A2 gene and a multihormonal regulatory region in the chicken II gene. AB - Expression of the vitellogenin genes in avian and amphibian liver is regulated by estrogens. The DNA elements mediating estrogen induction of the various vitellogenin genes of chicken and Xenopus encompass one or more copies of a 13 mer palindromic sequence called the estrogen-responsive element (ERE). Here we show that upon incubation with the purified estrogen receptor (ER) from calf uterus the Xenopus vitellogenin A2 gene yields a DNase-I footprint over the ERE between -331 and -319. This element does not mediate the response to glucocorticoids or progestins in T47D cells. The three guanine residues in each half of the palindrome are protected against methylation by dimethylsulfate after incubation with ER, but not with glucocorticoid (GR) or progesterone (PR) receptors. In contrast, the chicken vitellogenin II gene exhibits multihormonal regulation by estrogens, progestins, and glucocorticoids in T47D and MCF7 cells. Regulation is mediated by the DNA region between -721 and -591 that contains four binding sites for hormone receptors, as demonstrated by DNase-I footprints and methylation protection experiments. The two distal and most proximal binding sites are recognized by ER, GR, and PR, whereas the central binding site is only bound by ER and GR. At suboptimal concentrations, estrogens and progestins or glucocorticoids act synergistically. In experiments using a DNA fragment containing an ERE adjacent to a glucocorticoid-responsive element/progesterone responsive element, ER and PR bind synergistically to their corresponding sites, perhaps explaining the functional synergism of both hormones. Thus, two very different regulatory elements are used to mediate estrogen induction of related genes in chickens and amphibians. PMID- 1890990 TI - Ligand-induced down-regulation of testicular and ovarian luteinizing hormone (LH) receptors is preceded by tissue-specific inhibition of alternatively processed LH receptor transcripts. AB - Down-regulation of plasma membrane receptors by homologous hormones has been found in diverse cell types. In testicular Leydig and ovarian luteal cells, treatment with LH/hCG decreases LH receptor content. Although suppression of LH binding sites may result from ligand-induced receptor internalization, sequestration, and/or phosphorylation, the gonadotropins may also regulate receptor mRNA levels. We examined the regulation of testis LH receptor mRNAs in adult rats that received 10 or 200 IU hCG, using cRNA probes derived from the 5' extracellular domain (EC) or the 3' transmembrane domain (TM) of the rat receptor cDNA. Probe EC hybridized to predominant signals of 7 and 1.8 kilobases (kb) and weaker signals of 4.2 and 2.5 kb. However, probe TM hybridized to the three larger forms of the LH receptor mRNA, but not to the 1.8-kb species, suggesting that the latter form lacks the transmembrane domain. After 6 and 12 h of treatment with 200 or 10 IU hCG, respectively, hybridization to the larger mRNA species decreased by more than 60%, preceding decreases in testicular [125I]hCG binding. These transcripts were further inhibited (greater than 93%) between 24 72 h after hCG treatment and returned to 40% and 100% of control levels by days 6 and 9, respectively. In contrast, the truncated 1.8-kb LH receptor transcript was not affected by hCG treatment, indicating a differential suppressive effect of the ligand on its receptor mRNA levels. In the ovary, hybridization to probe EC revealed four transcripts with similar sizes as those found in the testes, with a predominant 7-kb species.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1890991 TI - Regulation of estrogen receptor messenger ribonucleic acid in rat hypothalamus by sex steroid hormones. AB - Sex steroid hormone receptors are thought to mediate the actions of their respective hormones by functioning as ligand-activated nuclear transcription factors that alter the expression of specific sets of hormone-responsive genes. Particularly high densities of estrogen receptor (ER)-containing neurons are located in the arcuate nucleus (ARH) and ventrolateral part of the ventromedial nucleus (VMHvl) of the hypothalamus, and these cell groups are thought to play key roles in the neuroendocrine control of reproductive function. Thus, hormonal regulation of ER gene expression in ARH and VMHvl neurons represents a direct mechanism by which circulating sex steroids could affect the responsiveness of these neurons to hormonal activation. We used in situ hybridization histochemistry to evaluate the influence of estradiol and testosterone on levels of ER mRNA within the ARH and VMHvl of adult male and female rats. In female rats, estradiol treatment reduced levels of ER mRNA in the ARH and VMHvl within 24 h relative to levels in both ovariectomized control animals and intact estrous females. Comparable results were obtained in male rats, except that testosterone did not significantly attenuate ER mRNA hybridization in the VMHvl until after 3 days of hormone treatment, and only a minor decrease was noted in the ARH, which was not statistically significant. In both male and female animals, the overall density of labeling found over individual cells in emulsion-dipped autoradiograms was consistently lower in hormone-treated animals compared with that over cells in gonadectomized controls, suggesting that the observed decreases in ER mRNA hybridization measured over the ARH and VMHvl are due to changes in cellular levels of ER mRNA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1890993 TI - AAEM minimonograph #11: Needle examination in clinical electromyography. AB - The physiologic and histologic principles underlying clinical electromyographic studies are briefly reviewed as an introduction to the normal and abnormal findings in human subjects. Technical aspects of recordings as well as the specific types of discharges and their significance are discussed. PMID- 1890992 TI - Isolation, characterization, and developmental expression of the rat peptide-YY gene. AB - In the present study we describe the isolation, structural characterization, and developmental expression of the gene encoding the intestinal hormone peptide-YY. Examination of the nucleotide sequence of the peptide-YY gene reveals that each of the four exons encodes a functional domain of its mRNA that is analogous to the corresponding exons of the genes encoding two closely related peptides neuropeptide-Y and pancreatic polypeptide. The highly conserved structural organization of the genes encoding this family of three peptides suggests that each gene arose from the duplication of a common ancestral gene. Developmental studies reveal that the peptide-YY gene exhibits a complex pattern of tissue specific expression in the gastrointestinal tract. Unlike many gastrointestinal hormones, peptide-YY mRNA levels are highest before birth. The pancreas appears to be the major site of peptide-YY gene expression in the fetus, exceeding colonic expression by 7-fold. The abundance of peptide-YY mRNA in the pancreas declines rapidly after birth, in contrast to the colon, where mRNA levels are maintained throughout development into adulthood. Expression of the peptide-YY gene before birth antedates the presence of known enteral secretagogues for this hormone, suggesting alternate mechanisms that control its biosynthesis during development. PMID- 1890995 TI - Large amplitude sensory action potentials in myelopathy: an observation. AB - Subjects with at least one sensory action potential (SAP) amplitude greater than 2 SD above the age-matched mean during standard nerve conduction tests were evaluated for evidence of spinal cord disease. From a total of 153 subjects, 16 had at least one large amplitude SAP and 12 of 16 (75%) had a documented myelopathy. While a mechanism has yet to be determined, this observation suggests that SAP amplitudes greater than 2 SD above normal may be correlated with clinical evidence of injury to the central nervous system. PMID- 1890994 TI - An endogenous inhibitor of calcium-activated neutral protease in UMX 7.1 hamster dystrophy. AB - An endogenous inhibitor for calcium-activated neutral protease (CANP) from skeletal and cardiac muscles of muscular dystrophic hamsters (UMX 7.1) was compared with that from normal control animals at 4 and 10 weeks of age by Western blotting using antibody raised against CANP inhibitor. Fragmented CANP inhibitor was found in dystrophic skeletal muscles in all cases at both ages, while only intact inhibitor was detected in the skeletal muscle of the normal hamsters. A total absence of intact inhibitor was shown in one 10-week-old dystrophic hamster. In contrast, there was little difference in CANP inhibitor from heart between dystrophic and control hamsters at 4 weeks. However, fragmentation similar to that in skeletal muscle was seen in the heart inhibitor in a few of the 10-week-old dystrophic hamsters. PMID- 1890996 TI - Magnetic resonance imaging of the muscles in patients with polymyositis and dermatomyositis. AB - Magnetic resonance imaging (MRI) of the muscles was performed in patients with polymyositis and dermatomyositis. Lesions with high intensity on T2-weighted image, but normal intensity on T1-weighted image, were observed in 7 of 8 patients in the active stage of the disease. Following clinical improvement with corticosteroid therapy in 4 patients, the high intensity lesions reverted to normal. The high intensity lesions seen on T2-weighted image in the active stage may represent edema and inflammation of the muscle. MRI of the muscle may serve as a diagnostic tool and be useful for follow-up of the patients with polymyositis or dermatomyositis. PMID- 1890997 TI - Magnetic stimulation of muscle evokes cerebral potentials. AB - Somatosensory evoked potentials (SEPs) were recorded from the scalp in man to magnetic stimulation of various skeletal muscles. The potentials consisted of several components, the earliest of which decreased in latency as the stimulated site moved rostrally, ranging from 46 msec for stimulation of the gastrocnemius, to 14 msec for stimulation of the deltoid. Experiments were performed to distinguish the mechanisms by which magnetic stimulation of the muscle was effective in evoking these cerebral potentials. For the gastrocnemius, the intensity of the magnetic stimulus needed for evoking cerebral potentials was less than that required for activating mixed or sensory nerves in proximity to the muscle belly (eg, posterior tibial nerve in the popliteal fossa, sural nerve at the ankle). Vibration of the muscle or passive lengthening of the muscle, procedures which activate muscle spindles, were accompanied by a significant attenuation of the potentials evoked by magnetic stimulation of the muscle. Anesthesia of the skin underlying the stimulating coil had no effect on the latency or amplitude of the early components of the magnetically evoked potentials, whereas electrically evoked potentials from skin electrodes were abolished. Thus, the cerebral potentials accompanying magnetic stimulation of the muscle appear to be due to activation of muscle afferents. We suggest that magnetic stimulation of muscle can provide a relatively simple method for quantifying the function of muscle afferents originating from a wide variety of skeletal musculature. PMID- 1890998 TI - Muscle fiber recovery functions studied with double pulse stimulation. AB - Direct electrical stimulation with paired pulses at varied intervals was used to study the propagation velocity and action potential amplitude recovery functions (VRF and ARF) of single muscle fibers. Following a subnormal period with slowed conduction, most of the muscle fibers tested in healthy subjects showed a period of supernormal propagation velocity starting at 3 to 12 ms, with a peak between about 5 and 15 ms, a mean increase of 7%, and an approximately logarithmic decay toward 1 second. The onset of supernormality was earlier in muscle fibers from patients with muscular dystrophy and significantly delayed in those from denervated muscles. Denervated muscle fibers also had a significantly longer refractory period. PMID- 1891000 TI - Relationship between electrical and vibratory output of muscle during voluntary contraction and fatigue. AB - Measurements were done on the biceps muscles of 6 healthy volunteers to record simultaneously the surface electromyogram (EMG) and vibromyogram (VMG) by means of a piezoelectric device (accelerometer). The VMG is generated by mechanical waves due to the contraction mechanism and often measured as sound. The frequency spectrum and integrated value (IEMG and IVMG) of both signals were calculated. Both IEMG and IVMG showed a clear linear correlation with force, although at high forces, the variability of the VMG became rather high. Two series of experiments were performed to study the EMG and VMG changes in relation to changes induced by fatigue: (1) during constant force at 50% of the maximal voluntary contraction (MVC) and recovery; (2) for one 1 minute during declining force at MVC. The main finding was that the IVMG was related to the absolute force, irrespective of the fatigue state of the muscle. In contrast, the IEMG showed the well-known changes during fatigue, such as an increase during endurance. The spectral changes of the two measurements also showed a divergence. The spectra of the EMG shifted to lower frequencies in both fatigue protocols. In contrast, the spectra of the vibratory signal did not shift, except for several measurements at MVC. However, the shape did change to a somewhat flatter spectrum with less pronounced peaks. Possible explanations for this different behavior are discussed. It is concluded that the vibratory energy generated by the contraction mechanism is linearly related to force. Changes induced by fatigue do not alter this relationship: this contrasts with the behavior of the EMG.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1890999 TI - Comparison of stimulation and insulin effects on denervated mouse soleus muscles. AB - A comparison has been made between the responses of denervated mouse soleus muscles to direct electrical stimulation, as reported by earlier workers, and to incubation with supraphysiological concentrations of insulin. The parameters of interest were resting membrane potential (RMP), qualities of the active state, the amount of alpha bungarotoxin (BUTX) binding, and chemosensitivity, as measured by the strength of acetylcholine (ACh)-induced contractures. In all aspects, the changes recorded after insulin, were in the same direction as with direct stimulation, however, owing to the time limitations of in vitro testing, were smaller. It is suggested that the effects of electric shocks on denervated muscles are the result of activation of the insulin receptor, or some similar macromolecule, which appears to be sensitive to the membrane potential. The possible interrelations between acetylcholine and insulin receptors in neurotrophic control are discussed. PMID- 1891002 TI - Vector short-latency somatosensory-evoked potentials. PMID- 1891001 TI - Glucocorticoids and immunosuppressants do not change the prevalence of necrosis and regeneration in mdx skeletal muscles. AB - Therapeutic doses of methylprednisolone, azathioprine, cyclosporin A, and cyclophosphamide administered to mdx mice between 15 and 45 days of age failed to significantly influence the time course and prevalence of necrosis and regeneration or serum creatine kinase activity. This finding contrasts with previously reported findings of beneficial effects of glucocorticoids in Duchenne muscular dystrophy (DMD). This may indicate that, mechanisms upon which beneficial effects of glucocorticoids depend in DMD, do not operate (sufficiently) in mdx mice. PMID- 1891003 TI - Adult metachromatic leukodystrophy and pes cavus foot deformity. PMID- 1891004 TI - Supermarket neuropathy. PMID- 1891005 TI - Comparison of thermography and electromyography. PMID- 1891006 TI - Abnormal coronary vasoconstriction as a predictor of restenosis after successful coronary angioplasty in patients with unstable angina pectoris. AB - BACKGROUND: High rates of restenosis after coronary angioplasty have been reported in patients with vasospastic angina. This study was designed to determine whether the occurrence of abnormal coronary vasoconstriction, detected by means of hyperventilation testing before angioplasty, influences the risk of restenosis after successful dilation. METHODS: Hyperventilation testing was performed 0 to 4 days before coronary angioplasty in 106 consecutive patients with unstable angina and single-vessel coronary artery disease. Abnormal coronary vasoconstriction was considered present if hyperventilation-induced myocardial ischemia occurred during the recovery phase of the test. All patients had follow up angiography 8 to 12 months after angioplasty. RESULTS: Abnormal coronary vasoconstriction was observed in 48 patients (group 1), whereas 58 patients (group 2) had either a negative response throughout the test or a positive response only during the overbreathing phase of the hyperventilation test. Angioplasty was successful in 40 patients in group 1 and 51 in group 2. Restenosis was documented in 29 patients (73 percent) in group 1 and 13 (25 percent) in group 2 (relative risk of restenosis, 2.84; 95 percent confidence interval, 1.69 to 4.28; P less than 0.001). In a multivariate analysis, the following three characteristics were independently related to the risk of restenosis (in descending order of importance): ST-segment elevation during spontaneous ischemic attacks (P less than 0.001), hyperventilation-induced abnormal coronary vasoconstriction (P less than 0.001), and the presence of a lesion more than 10 mm long in the left anterior descending coronary artery (P less than 0.05). CONCLUSIONS: In patients with unstable angina and single-vessel coronary artery disease who have been selected for coronary angioplasty, the presence of hyperventilation-induced abnormal coronary vasoconstriction identifies a subgroup at high risk for restenosis. PMID- 1891007 TI - Long-term follow-up after partial removal of a solitary kidney. AB - BACKGROUND: The removal of more than one kidney in animals leads to proteinuria and progressive renal failure due to focal segmental glomerulosclerosis. This injury may be the result of chronic glomerular hyperfiltration. The purpose of this study was to determine the effect of a reduction in renal mass of more than 50 percent on residual renal function and morphology in humans. METHODS: We evaluated long-term renal function in 14 patients with a solitary kidney who had undergone partial nephrectomy for renal-cell or transitional-cell carcinoma. In 12, the first kidney had been removed 2 months to 21 years previously for the same type of cancer; in 2, the other kidney was congenitally atrophic. Before surgery, no patient had clinical or histopathological evidence of primary renal disease. All 14 patients underwent partial nephrectomy to remove a localized tumor, with 25 to 75 percent of the solitary kidney being excised. They were evaluated 5 to 17 years after surgery (mean, 7.7). RESULTS: Twelve patients had stable postoperative renal function, and end-stage renal failure developed in two. There were no changes in blood pressure in any patient during follow-up. Nine patients had proteinuria, which was mild (0.15 to 0.8 g of urinary protein per day) in five. The extent of proteinuria was inversely correlated with the amount of remaining renal tissue (P = 0.0065) and directly correlated with the duration of follow-up (P = 0.0005). Four patients with moderate-to-severe proteinuria had renal biopsies, which revealed focal segmental glomerulosclerosis in three patients and global glomerulosclerosis in one. CONCLUSIONS: Long-term renal function remains stable in most patients with a reduction in renal mass of more than 50 percent. These patients are, however, at increased risk for proteinuria, glomerulopathy, and progressive renal failure. PMID- 1891008 TI - Relation between airway responsiveness and serum IgE in children with asthma and in apparently normal children. AB - BACKGROUND: Although asthma diagnosed by a physician is known to be related to serum IgE levels, it is not known whether there is a relation between the level of IgE and airway hyperresponsiveness to a methacholine challenge. The characteristics of asymptomatic persons that predispose them to airway hyperresponsiveness are also unknown. METHODS: We studied the relation between the serum total IgE level and airway hyperresponsiveness in the presence or absence of asthma and other atopic diseases in a birth cohort of children. Data from a questionnaire regarding respiratory symptoms, plus measurements of the serum total IgE level and airway responsiveness to inhaled methacholine, were obtained for 562 11-year-olds in New Zealand. RESULTS: The boys had a higher prevalence than the girls of current diagnosed asthma (13 percent vs. 6 percent), current symptoms of wheezing (22 percent vs. 15 percent), and airflow obstruction at base line (6 percent vs. 1 percent) and had a wider distribution of IgE levels, although mean IgE levels (120.8 IU per milliliter in the boys and 98.1 IU per milliliter in the girls) did not differ significantly between the sexes. The prevalence of diagnosed asthma was strongly related to the serum IgE level (P for trend less than 0.0001). No asthma was reported in children with IgE levels less than 32 IU per milliliter, whereas 36 percent of those with IgE levels greater than or equal to 1000 IU per milliliter were reported to have asthma. This relation with the serum IgE level was not explained by a concomitant diagnosis of allergic rhinitis or eczema. Airway hyperresponsiveness to a methacholine challenge also correlated very highly (P less than 0.0001) with the serum IgE level. This relation remained significant even after the exclusion of children with diagnosed asthma (P less than 0.0001) and of all children with a history of wheezing, allergic rhinitis, or eczema (P less than 0.0001). CONCLUSIONS: Even in children who have been asymptomatic throughout their lives and have no history of atopic disease, airway hyperresponsiveness appears to be closely linked to an allergic diathesis, as reflected by the serum total IgE level. PMID- 1891009 TI - Effects of Medicaid drug-payment limits on admission to hospitals and nursing homes. AB - BACKGROUND: Many state Medicaid programs limit the number of reimbursable medications that a patient can receive. We hypothesized that such limitations may lead to exacerbations of illness or to admissions to institutions where there are no caps on drug reimbursements. METHODS: We analyzed 36 months of Medicaid claims data from New Hampshire, which had a three-drug limit per patient for 11 of those months, and from New Jersey, which did not. The study patients in New Hampshire (n = 411) and a matched comparison cohort in New Jersey (n = 1375) were Medicaid recipients 60 years of age or older who in a base-line year had been taking three or more medications per month, including at least one maintenance drug for certain chronic diseases. Survival (defined as remaining in the community) and time-series analyses were conducted to determine the effect of the reimbursement cap on admissions to hospitals and nursing homes. RESULTS: The base-line demographic characteristics of the cohorts were nearly identical. In New Hampshire, the 35 percent decline in the use of study drugs after the cap was applied was associated with an increase in rates of admission to nursing homes; no changes were observed in the comparison cohort (RR = 1.8; 95 percent confidence interval, 1.2 to 2.6). There was no significantly increased risk of hospitalization. Among the patients in New Hampshire who regularly took three or more study medications at base line, the relative risk of admission to a nursing home during the period of the cap was 2.2 (95 percent confidence interval, 1.2 to 4.1), and the risk of hospitalization was 1.2 (95 percent confidence interval, 0.8 to 1.6). When the cap was discontinued after 11 months, the use of medications returned nearly to base-line levels, and the excess risk of admission to a nursing home ceased. In general, the patients who were admitted to nursing homes did not return to the community. CONCLUSIONS: Limiting reimbursement for effective drugs puts frail, low-income, elderly patients at increased risk of institutionalization in nursing homes and may increase Medicaid costs. PMID- 1891010 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 41-1991. A 76-year-old man with recurrent gastrointestinal bleeding. PMID- 1891011 TI - How little kidney tissue is enough? PMID- 1891012 TI - On squeezing balloons. Cost control fails again. PMID- 1891013 TI - Rational suicide and the right to die. Reality and myth. PMID- 1891014 TI - The effect of unproved cancer therapy in advanced cancer. PMID- 1891015 TI - Surfactant-replacement therapy. PMID- 1891016 TI - Pseudohyperkalemia and platelet counts. PMID- 1891017 TI - Dysphagia in the post-polio syndrome. PMID- 1891018 TI - Identification of Ehrlichia in human tissue. PMID- 1891019 TI - Cardiogenic shock after acute myocardial infarction. Incidence and mortality from a community-wide perspective, 1975 to 1988. AB - BACKGROUND: Cardiogenic shock resulting from acute myocardial infarction is a serious complication with a high mortality rate, but little is known about whether its incidence or outcome has changed over time. As part of an ongoing population-based study of acute myocardial infarction, we examined trends over time in the incidence and mortality rate of cardiogenic shock after acute myocardial infarction. METHODS: We studied 4762 patients with acute myocardial infarction who were admitted to 16 hospitals in the Worcester, Massachusetts, metropolitan area between 1975 and 1988. We determined the incidence of and short term and long-term mortality due to cardiogenic shock in each of six years during this study period. RESULTS: The incidence of cardiogenic shock complicating acute myocardial infarction remained relatively constant, averaging 7.5 percent. Multivariate regression analysis that controlled for variables affecting incidence revealed significant though inconsistent temporal trends in the incidence of cardiogenic shock. As compared with the risk in 1975, the adjusted relative risk (with 95 percent confidence interval) was 0.83 (0.54 to 1.28) in 1978, 0.96 (0.63 to 1.48) in 1981, 0.68 (0.42 to 1.12) in 1984, 1.16 (0.70 to 1.92) in 1986, and 1.65 (0.99 to 2.77) in 1988. The overall in-hospital mortality rate among patients with cardiogenic shock was significantly higher than that among patients without this complication (77.7 percent vs. 13.5 percent, P less than 0.001). The in-hospital mortality among the patients with shock did not improve between 1975 (73.7 percent) and 1988 (81.7 percent). Long-term survival during the 14-year follow-up period was significantly worse among patients who survived cardiogenic shock during hospitalization than among patients who did not have shock (P less than 0.001). CONCLUSIONS: The results of this observational, community-wide study suggest that neither the incidence nor the prognosis of cardiogenic shock resulting from acute myocardial infarction has improved over time. Both in-hospital and long-term survival remain poor for patients with this complication. PMID- 1891020 TI - Helicobacter pylori infection and the risk of gastric carcinoma. AB - BACKGROUND: Infection with Helicobacter pylori has been linked with chronic atrophic gastritis, an inflammatory precursor of gastric adenocarcinoma. In a nested case-control study, we explored whether H. pylori infection increases the risk of gastric carcinoma. METHODS: From a cohort of 128,992 persons followed since the mid-1960s at a health maintenance organization, 186 patients with gastric carcinoma were selected as case patients and were matched according to age, sex, and race with 186 control subjects without gastric carcinoma. Stored serum samples collected during the 1960s were tested for IgG antibodies to H. pylori by enzyme-linked immunosorbent assay. Data on cigarette use, blood group, ulcer disease, and gastric surgery were obtained from questionnaires administered at enrollment. Tissue sections and pathology reports were reviewed to confirm the histologic results. RESULTS: The mean time between serum collection and the diagnosis of gastric carcinoma was 14.2 years. Of the 109 patients with confirmed gastric adenocarcinoma (excluding tumors of the gastroesophageal junction), 84 percent had been infected previously with H. pylori, as compared with 61 percent of the matched control subjects (odds ratio, 3.6; 95 percent confidence interval, 1.8 to 7.3). Tumors of the gastroesophageal junction were not linked to H. pylori infection, nor were tumors in the gastric cardia. H. pylori was a particularly strong risk factor for stomach cancer in women (odds ratio, 18) and blacks (odds ratio, 9). A history of gastric surgery was independently associated with the development of cancer (odds ratio, 17; P = 0.03), but a history of peptic ulcer disease was negatively associated with subsequent gastric carcinoma (odds ratio, 0.2; P = 0.02). Neither blood group nor smoking history affected risk. CONCLUSIONS: Infection with H. pylori is associated with an increased risk of gastric adenocarcinoma and may be a cofactor in the pathogenesis of this malignant condition. PMID- 1891021 TI - Helicobacter pylori infection and gastric carcinoma among Japanese Americans in Hawaii. AB - BACKGROUND: Helicobacter pylori are gram-negative spiral bacteria that are associated with chronic gastritis, a known precursor of gastric carcinoma. Persons at high risk for gastric carcinoma have been shown to have a high prevalence of H. pylori infection. METHODS: We studied the relation of H. pylori infection and gastric carcinoma in a cohort of Japanese American men living in Hawaii. The 5908 men were enrolled and examined from 1967 to 1970. By 1989, 109 cases of pathologically confirmed gastric carcinoma had been identified. The store serum of each patient with gastric carcinoma and of each matched control subject were tested for the presence of serum IgG antibody to H. pylori. RESULTS: Ninety-four percent of the men with gastric carcinoma and 76 percent of the matched control subjects had a positive test for H. pylori antibodies, for an odds ratio of 6.0 (95 percent confidence interval, 2.1 to 17.3). As the level of antibody to H. pylori increased, there was a progressive increase in the risk of gastric carcinoma (P for trend = 0.0009). The association was strong even for men in whom the diagnosis was made 10 or more years after the serum sample was obtained (odds ratio, 10.5; 95 percent confidence interval, 2.5 to 44.8). CONCLUSIONS: Infection with H. pylori is strongly associated with an increased risk of gastric carcinoma. However, most persons infected with H. pylori will never have gastric carcinoma. Therefore, other factors that increase the risk of gastric carcinoma among persons infected with H. pylori need to be identified. PMID- 1891023 TI - Gastrointestinal endoscopy (1) PMID- 1891022 TI - Suppression of thromboxane A2 but not of systemic prostacyclin by controlled release aspirin. AB - BACKGROUND: The antithrombotic efficacy of aspirin is attributed to its inhibition of the enzyme prostaglandin G/H synthase, which is necessary for the formation of thromboxane A2 in platelets. Thromboxane A2 is a potent vasoconstrictor and platelet agonist. However, the formation of prostacyclin by vascular endothelium also requires prostaglandin G/H synthase, and prostacyclin exerts opposite effects on platelet function and vascular tone. We wanted to see whether controlled-release aspirin would affect the formation of thromboxane A2 but not prostacyclin by reducing the aspirin concentration that reaches the posthepatic circulation. METHODS: A controlled-release formulation containing 75 mg of aspirin, designed to release 10 mg per hour, was developed to inhibit prostaglandin G/H synthase in platelets in the prehepatic circulation. The effects of the controlled-release preparation on plasma levels of aspirin and salicylate, serum levels of thromboxane B2, and urinary dinor metabolites of prostacyclin and thromboxane B2 (measured by gas chromatography-mass spectrometry) were compared with those of conventional immediate-release aspirin in normal volunteers. Prostacyclin release was stimulated by intravenous bradykinin. RESULTS: Steady-state inhibition of serum thromboxane B2 required two to four days and appeared slower with 75 mg of controlled-release than with the same amount of immediate-release aspirin. Maximal inhibition was achieved rapidly by adding a single loading dose of 162.5 mg of immediate-release aspirin to the regimen. Over a 28-day period, suppression of thromboxane A2 with this regimen was comparable to that with immediate-release aspirin taken either as 162.5 mg daily or as 325 mg on alternate days, despite the minimal systemic bioavailability of controlled-release aspirin. Bleeding time was prolonged to a similar degree with each of the three regimens. The five- to sixfold increase in the prostacyclin metabolite induced by bradykinin was depressed by pretreatment for four days with 75 mg of immediate-release aspirin, but not by 75 mg of controlled-release aspirin. CONCLUSIONS: Maximal inhibition of platelet thromboxane A2 production was sustained during long-term dosing with controlled release aspirin, whereas basal prostacyclin biosynthesis fell only slightly and systemic synthesis of prostacyclin stimulated by bradykinin was preserved. Controlled-release aspirin may facilitate determination of the clinical importance of preserving prostacyclin during platelet inhibition in humans. PMID- 1891024 TI - Sickle cell disease in a patient with sickle cell trait and compound heterozygosity for hemoglobin S and hemoglobin Quebec-Chori. PMID- 1891025 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 42-1991. A 63-year-old obese diabetic woman with a pleura-based mass in the right upper lobe. PMID- 1891026 TI - Reducing mortality in patients with extensive myocardial infarction. PMID- 1891027 TI - Is gastric carcinoma an infectious disease? PMID- 1891028 TI - Provocation testing and food sensitivity. PMID- 1891029 TI - Erythropoietin in anemia of renal failure in sickle cell disease. PMID- 1891030 TI - Erythropoietin. PMID- 1891031 TI - Biotechnology--the enormous cost of success. PMID- 1891032 TI - Acute renal failure and coma after a high dose of oral acyclovir. PMID- 1891033 TI - A reduction in verapamil concentrations with phenytoin. PMID- 1891034 TI - Importance of the lay press in the transmission of medical knowledge to the scientific community. AB - BACKGROUND: Efficient, undistorted communication of the results of medical research is important to physicians, the scientific community, and the public. Information that first appears in the scientific literature is frequently retransmitted in the popular press. Does popular coverage of medical research in turn amplify the effects of that research on the scientific community? METHODS: To test the hypothesis that researchers are more likely to cite papers that have been publicized in the popular press, we compared the number of references in the Science Citation Index to articles in the New England Journal of Medicine that were covered by The New York Times with the number of references to similar articles that were not covered by the Times. We also performed the comparison during a three-month period when the Times was on strike but continued to prepare an "edition of record" that was not distributed; doing so enabled us to address the possibility that coverage in the Times was simply a marker of the most important articles, which would therefore be cited more frequently, even without coverage in the popular press. RESULTS: Articles in the Journal that were covered by the Times received a disproportionate number of scientific citations in each of the 10 years after the Journal articles appeared. The effect was strongest in the first year after publication, when Journal articles publicized by the Times received 72.8 percent more scientific citations than control articles. This effect was not present for articles published during the strike; articles covered by the Times during this period were no more likely to be cited than those not covered. CONCLUSIONS: Coverage of medical research in the popular press amplifies the transmission of medical information from the scientific literature to the research community. PMID- 1891035 TI - Biotechnology. Go-ahead for Centocor. PMID- 1891036 TI - Japanese science budget. Good news for universities. PMID- 1891037 TI - Powdered milk. PMID- 1891038 TI - Vitamins and intelligence tests. PMID- 1891039 TI - Baer facts. PMID- 1891040 TI - Why scientists cover up fraud. PMID- 1891041 TI - Nature's manifesto for British science. PMID- 1891042 TI - Japan's graduate university matures. PMID- 1891043 TI - Language origins. The silence of the past. PMID- 1891044 TI - Human genetics. Language of the genome. PMID- 1891045 TI - MHC class II structure, occupancy and surface expression determined by post endoplasmic reticulum antigen binding. AB - Class II major histocompatibility complex molecules undergo a change in structure upon stable binding of peptide antigen. Analysis of the site and extent of this change among class II molecules of splenic antigen-presenting cells reveals the preference of class II for peptide acquisition outside the endoplasmic reticulum and indicates that the class II presentation system is not saturated with self peptides. There are numerous empty class II molecules on the cell surface and peptide antigen is evidently important in regulating surface class II expression. PMID- 1891046 TI - Double cones as a basis for a new type of polarization vision in vertebrates. AB - Many invertebrates and vertebrates are sensitive to the polarization of light. The biophysical basis of invertebrate polarization sensitivity is an intrinsic dichroism, the alignment of chromophores along the photoreceptor microvilli. But such dichroism to axially propagating light is not present in vertebrate photoreceptors, whose chromophores are free to rotate in the plane of the outer segment disc membranes, and a biophysical mechanism responsible for vertebrate polarization sensitivity has not been established. We hypothesize that the roughly elliptical cross-sectioned double-cone inner segment acts as a birefringent, polarization-sensitive dielectric waveguide, and that the double cone mosaic generates a 'polarization contrast' neural image. Here we confirm three predictions derived from these hypotheses: (1) 90 degrees periodicity for polarization sensitivity; (2) polarization sensitivity maxima corresponding to the absolute orientation of the axes of the double-cone inner-segment cross sections; and (3) action spectrum for polarization sensitivity corresponding to the absorption spectrum of the double cones. We also present evidence for a polarization-opponent neural encoding in vertebrates. PMID- 1891047 TI - Scientific visualization: practices and promises. PMID- 1891049 TI - AIDS talk goes on. PMID- 1891050 TI - [Histological diagnosis of brain tumors: (17). Subependymal giant cell astrocytoma]. PMID- 1891051 TI - [Evaluation of CT-guided stereotactic hematoma aspiration in mild cases with putaminal hemorrhage]. AB - Reported here is the effectiveness of surgical management in mild cases with putaminal hemorrhage (neurological grading 1 or 2, described by Kanaya, et al.). Ten cases were treated by CT-guided stereotactic hematoma aspiration (aspiration group), and another 10 cases were treated by only medical therapy (conservative group). The mean interval from the onset to operation was 7.2 days. In both groups, serial change in the motor function of the upper extremity was examined and the neuropsychological function was also evaluated at 2 weeks after onset. Perifocal low-density area around the hematoma was estimated on CT scan at 2 weeks after onset. Mean hemispheric cerebral blood flow (mCBF) was measured at 5 days, 2 weeks and 6 months after onset, respectively in each group. The activity of daily life (ADL) was evaluated at 6 months after onset. There was no statistically significant difference in age, neurological grading and CT findings on admission between the 2 groups. At 2 weeks after onset, no case had deteriorated in motor function in the aspiration group. On the other hand, 2 cases had deteriorated in the conservative group. The neuropsychological function was considerably improved in the majority of cases in the aspiration group. Perifocal low area was significantly narrow on CT scan in the aspiration group. At 2 weeks after onset, the mCBF of the affected side was 53.8 +/- 6.0 ml/100g/min in the aspiration group, whereas it was 42.0 +/- 5.7 ml/100g/min in the conservative group. This difference was statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1891053 TI - [Clinicopathological studies of three cases of cerebral aneurysms associated with systemic lupus erythematosus]. AB - We report three cases of ruptured cerebral aneurysms associated with systemic lupus erythematosus (SLE). A 52-year-old woman (case 1) with a fifteen-year history of systemic lupus erythematosus suddenly lost consciousness. She was admitted in a state of deep coma. A computed tomography (CT) scan revealed acute hydrocephalus and diffuse subarachnoid hemorrhage in the basal, interhemispheric and bilateral Sylvian cisterns. Fifteen years prior to this admission, cerebral angiograms demonstrated no cerebral aneurysm. She underwent ventricular drainage immediately. Postoperatively, her condition did not improve, and she died on the 18th day. During the autopsy, two saccular cerebral aneurysms were found: one aneurysm was at the right middle cerebral artery bifurcation, and another one was on the anterior communicating artery, which had disruption of the internal elastic lamina and medial smooth muscle, and infiltration of inflammatory cells. In the major cerebral arteries, for example the bilateral internal carotid arteries, disruption or dissection of the internal elastic lamina, intimal fibrosis and transmural infiltration of inflammatory cells were observed. The second patient, a 36-year-old woman with a six-year history of SLE, was admitted to our hospital with sudden severe headache. A CT scan showed subarachnoid hemorrhage, and cerebral angiograms disclosed saccular cerebral aneurysms on the anterior communicating artery and the left superior cerebellar artery, and a fusiform one on the left posterior cerebral artery. Surgery was not recommended because of her multiple medical problems. Her consciousness improved gradually over 2 months. She was transferred to the department of internal medicine for treatment of renal failure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1891052 TI - [Experimental study on brain damage by extracerebral compression; alteration of cerebral circulation and microvascular architectures]. AB - Effects of extracerebral compression on cerebral circulation and microvascular architectures were investigated in 23 adult cats. Brain compression was produced by inserting 12 steel balls (5 mm in diameter) into the extradural space through a burr hole at the left temporal bone. One ball was inserted every 10 minutes. Mean arterial blood pressure (MABP), intracranial pressure (ICP) and cerebral blood flow (CBF) were measured continuously. Cerebral perfusion pressure (CPP) and cerebrovascular resistance (CVR) were then calculated. Microvascular architectures of the brain were studied by scanning electron microscopy (SEM) with cerebrovascular casting methods. CBF decreased significantly on the compressed side though CPP remained unchanged till 5 balls had been inserted. CVR increased correlatively to the numbers of balls on the compressed side while remaining unchanged during insertion of the balls on the contralateral side. In SEM study, flection and interruption of capillaries and compressed phenomenon of veins were most remarkable on the compressed side. Alterations of microvascular architectures correspond to cortical deformity in degree. These data show that increase of CVR correlating to alteration of microvascular architectures plays an important role in decrease of CBF in a compressed brain. It is thus suggested that intracranial mass lesion causing deformity of the brain must be removed in order to avoid further brain tissue damage due to microvascular lesions. PMID- 1891054 TI - [Clinical analysis of cerebral infarction in children]. AB - Six cases of cerebral occlusive disease in children were reported. The cerebral arterial occlusive disease had its onset at the age of less than 4 years, except for one case of a 9 year-old. The causes of occlusion were, trauma in two cases, infectious disease in one case, intraarterial myxoma in one case and an unknown reason in two cases. Initial symptoms were sudden onset of hemiplegia in 5 cases, and headache in one case. Angiography revealed stenosis of the main trunk of the middle cerebral artery, or of the anterior cerebral artery in 4 cases. Angiographical manifestations of stenosis in 4 cases were classified into two types, diffuse stenosis and localized stenosis. No stenotic changes were demonstrated in two cases, in which CT revealed a small low density area in the putamen. Follow up angiogram in three cases revealed improvement of stenosis. Though therapy in all cases was conservative, their prognosis is not so poor as had been considered. As the rate of recanalization in children was assumed to be high as compared with adult cases, it was considered that surgical revascularization in the acute stage had to be undergone very carefully. PMID- 1891055 TI - [A case of brain metastasis of rhabdomyosarcoma in a child]. AB - We report here a specific case of metastatic brain tumor orienting from rhabdomyosarcoma. An 11-year-old boy came to our hospital with complaints including headache, exophthalmos and tumors in the right frontal and left occipital region. 6 months previously subtotal removal of rhabdomyosarcoma in his right foot had been performed. CT scan demonstrated tumors in the right orbit, right frontal region and left occipital region. The tumors existed bilaterally in the skull and markedly enhanced by contrast medium. But the changes of the cranium were mild, only the dipole was slightly dilated. MRI showed that the tumors were extraaxial masses. Right external carotid angiogram revealed numerous tumor vessels fed by the meningeal artery. On April 3rd, biopsy was performed at the right frontal region. The tumor had spread in the epidural space but the cortical surface seemed to be intact. Histologically, the tumor consisted of small round cells and revealed multinuclear giant cells. It involved the skull bone, dura mater and subdural tissues. Accordingly the tumor was diagnosed as rhabdomyosarcoma. Although tumor increased rapidly, the intracranial region did not change remarkably. It was an interesting phenomenon. Eventually, rhabdomyosarcoma metastasized to the lung, and the patient died due to respiratory distress. PMID- 1891056 TI - [Repair of widely infected scalp defect and osteomyelitis with free radial forearm flap: a case report]. AB - A 60-year-old female was admitted with large frontal scalp defect associated with osteomyelitis due to chronic infection. Debridement of the infected scalp and frontal bone and the transplantation of the free radial forearm flap with vascular anastomosis was carried out. The wound cured uneventfully. Cranioplasty was performed ten months after the first operation. Transplantation of free radial forearm flap was first reported in 1982 by Song in China and has proved to be a very effective operative method, especially for the repair of large infected wounds. This is because good blood supply results from the anastomosis of larger vessels, and its cleansing effects can eradicate infections and prompt rapid wound healing. PMID- 1891057 TI - [Involuntary movement complicated with the postoperative stage of ruptured aneurysm: a case report]. AB - Involuntary movement complicated with the postoperative stage of the ruptured cerebral aneurysm is extremely rare. And, the pathophysiology of the involuntary movement has not been established yet. The authors report such a case because of its rarity and to make the mechanism of its appearance clear. The case was a 45 year-old female who was transported to our clinic after the onset of sudden headache. On admission, she had no neurological deficits without severe headache. CT scan revealed subarachnoid hemorrhage, and left carotid angiogram showed an aneurysm at the bifurcation of the left internal carotid artery. On the day of admission, neck clipping for the aneurysm was successfully performed. Postoperative course was uneventful without mild right hemiparesis which diminished until two weeks after operation. Since the 24th day from operation, athetoid involuntary movement occurred to her four toes. 123I-IMP SPECT revealed low perfusion from left frontal base to caudate, and CT scan showed atrophy of the left caudate. Athetoid involuntary movement as postoperative complication of ruptured cerebral aneurysm has not been reported without our case. We suppose it was caused by the ischemic effect of the left caudate due to the operative retraction or the delayed vasospasm after subarachnoid hemorrhage. PMID- 1891058 TI - [A case of bacterial aneurysm following Hardy's operation]. AB - Intracranial mycotic aneurysm of extravascular origin is reported. A 64 year-old male developed headache and visual disturbance. Computed Tomography (CT) revealed high density mass lesion with contrast enhancement in the intra- and suprasellar lesion. He was then admitted to our hospital under the diagnosis of pituitary adenoma. But he suddenly complained of headache and loss of vision during hospitalization. An emergency operation using the transsphenoidal approach was performed. The pathological diagnosis was craniopharyngioma. Postoperative radiation therapy was carried out using a tumor dose of 50Gy. Two months after the operation, he suffered from rhinorrhea and high fever. He was admitted again and treated with high doses of antibiotics. Two weeks after admission, he suddenly lost consciousness. A CT scan revealed an aneurysm of the anterior temporal artery. Immediately, removal of the hematoma and resection of the aneurysm were performed. Microscopic examination showed that inflammatory cells had infiltrated the aneurysmal wall, and lymphocytes and plasma cells had gathered around the microabscess. This rare case is discussed with other related cases in the literature. PMID- 1891060 TI - [Multilocular encapsulated intracerebral hematoma; a case report]. AB - Encapsulated intracerebral hematomas mimicking a brain tumor have been reported as a rare occurrence. An additional case with a characteristic feature found on computed tomography (CT), and a clinical course is described. CT scans revealed a high density mass with peripheral low density in the brain. A hematoma was successfully removed and found to have a thick and multilobular fibrous capsule associated with cavernous hemangioma. Repeated hemorrhage due to vascular malformation was considered to have contributed to the formation of the capsule. Increasing awareness of the possibility of an encapsulated intracerebral hematoma as a clinical and pathological entity, would enable us to make a correct diagnosis and to select proper treatment. A thorough survey of occult vascular malformation is necessary in surgery. PMID- 1891059 TI - [Multiple liver metastases of a suprasellar germ cell tumor treated with combined chemotherapy of cisplatin and etoposide]. AB - A 23-year-old man was admitted with progressively disturbed vision and easy fatigability. CT scans demonstrated an enhanced mass in the sellar region. Physical and endocrinological examinations revealed atrophy of both optic nerves, temporal field cuts in both eyes, and panhypopituitarism. Concentrations of human chorionic gonadotropin (HCG) in the serum and cerebrospinal fluid were 12 and 33IU/L, respectively. On November 11, 1987, the tumor was partially removed using the transsphenoidal approach. The histological diagnosis was germinoma with syncytiotrophoblastic giant cells. Following postoperative craniospinal irradiation (whole brain, 30Gy; local, 18Gy; spinal canal 28Gy), CT scans showed no residual tumor and the HCG levels decreased until they were undetectable. Eighteen months later, the patient complained of abdominal pain. His serum HCG level had increased to 2,554 IU/L. CT scans of the abdomen revealed multiple low density areas in the liver. Chest X-ray was negative. A Ga scintigram disclosed only liver metastasis. Administration of a chemotherapy was started on June 26, 1989. Cisplatin and etoposide in doses of 20mg and 40mg respectively were given for 5 consecutive days in one course. Following four courses of the combined chemotherapy, the tumor entirely disappeared on CT scans and the HCG level returned to normal. The patient is now able to work well without evidence of recurrence. Multiple liver metastases of an intracranial germ cell tumor had been fatal in previous reports. This may be the first case with liver metastases in which the victim is still alive. The present case indicates that combined chemotherapy with cisplatin and etoposide is effective for extraneural metastases of an intracranial germ cell tumor. PMID- 1891061 TI - [Successful treatment of huge arteriovenous malformation in the basal ganglia]. AB - This report describes successful therapeutic results of a huge and high flow arteriovenous malformation (AVM) in the left basal ganglionic region. A 39-year old female was admitted to our hospital presenting recent progression of aphasia, hemianopsia, hemiparesis, hemisensory disturbance on the right side. Progression of disturbance in consciousness was rapid, and the patient became comatose shortly after admission. A CT scan revealed a densely enhanced lesion in the left basal ganglia which caused aqueductal obstruction and hydrocephalus. Angiography demonstrated a huge and high flow AVM that was supplied by the anterior and posterior choroidal arteries, the lateral striate arteries and the insular branches of the middle cerebral arteries. This AVM drained into the vein of Galen via the inferior ventricular and basal vein. The draining vein was markedly dilated at the level of midbrain by a prominent stenosis of the junction between the vein of Galen and straight sinus, and it severely compressed the midbrain. Superselective embolization of the feeding arteries was done in two sessions. This was followed by surgical intervention for the embolized AVM one month after the second session. Embolization and surgery were carried out under barbiturate protection to reduce the risk of normal perfusion pressure break-through. The patient recovered well from these interventions without any hemodynamic changes and showed dramatic improvement of all focal neurological abnormalities. Postoperative angiography showed only a small residue of AVM. PMID- 1891062 TI - [A case of adult pilocytic astrocytoma in the right temporal lobe]. AB - A case of adult pilocytic astrocytoma in the right temporal lobe is reported here. The patient was a twenty-four year old man, who came to the neurological division of our hospital on October 6, 1987 because of repeated consciousness loss attacks accompanied with uncinate fit. He had no neurological deficits. However, an EEG revealed spike-and-wave complexes in the right temporal region, and a CT scan showed a small cystic lesion in the right temporal lobe. A diagnosis of psychomotor seizure was made, and the administration of anticonvulsants was started. The incidence of attack then decreased, but after approximately two years of drug therapy the attacks increased again. A CT scan was again performed, and revealed that the lesion in the right temporal lobe was enlarging. Also a noticeable enhanced lesion, identified as a mural nodule was found in the post-contrast enhancement study. A brain tumor was then suspected, and he was admitted to the neurosurgical division on October 11, 1989. He had no neurological deficits on admission. An MRI showed a low intensity lesion in the T1 weighted image, and a high intensity lesion in the T2 weighted image. A cystic lesion with a marked enhanced mural nodule was also found in the base of the right temporal lobe, according to the Gd enhancement study. Perifocal edema was not recognized. Cerebral angiography showed no positive findings. Positron emission tomography (PET), using H2(15)O, revealed low perfusion at or around the lesion, and PET using [11C]-methionine revealed an accumulation of methionine at the lesion. A diagnosis of low-grade glioma was made, and a right temporal craniotomy, for the purpose of totally removing the tumor was performed on October 26, 1989.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1891064 TI - Neuronal hypertrophy in the pars reticulata of the substantia nigra in Parkinson's disease. AB - The size of neurons in the pars reticulata of the substantia nigra in patients dying with Parkinson's disease has been compared with that in non-parkinsonian control cases. Parkinson's disease is accompanied by a significant (+53%) hypertrophy of reticulata neurons. This is similar to changes seen in experimental rats with ipsilateral damage of the striatum. It is suggested that the enlargement seen in Parkinson's disease, similar to that in the rat, is indicative of plasticity in the GABA-ergic reticulata neurons, and may be associated with increased inhibitory flux in pathways arising from the pars reticulata to the superior colliculus and thalamus. PMID- 1891063 TI - Widespread serum amyloid P immunoreactivity in cortical amyloid deposits and the neurofibrillary pathology of Alzheimer's disease and other degenerative disorders. AB - Amyloid P (AP) component is present in all types of systemic amyloid deposits. Recently, it has been shown to be also present in cerebral amyloid lesions of Alzheimer's disease (AD). In this study, we used immunocytochemical methods to extend these findings at the electron microscope level and characterize the spectrum of AP immunoreactivity in neurofibrillary pathology (NFP) of AD and other neurodegenerative disorders including Down's syndrome (DS), Creutzfeldt Jakob, Parkinson's, Pick's and diffuse Lewy body diseases and progressive supranuclear palsy. In AD and DS, AP immunoreaction product was evident in all the classical amyloid lesions and NFP in a large sample of all cortical areas examined. The distribution and relative intensity of immunostaining was similar to that of thioflavin S staining in serial sections. In many cases, however, plaques and vessels stained by anti-AP serum were not apparent with thioflavin S. Serial sections immunostained with antiserum to amyloid A, C-reactive protein or to other proteins involved in systemic amyloidoses and the acute phase response showed no evidence of staining in any of the cerebral lesions. Electron microscopy confirmed that AP immunoreactivity was associated with the abnormal filaments characteristic of NFP as well as amyloid fibrils found in plaques and vessels showing congophilic amyloid angiopathy. Plaques of Creutzfeldt-Jakob disease, Pick bodies of Pick's disease, tangles and Lewy bodies in Parkinson's disease and a subpopulation of Lewy bodies in the diffuse Lewy body disease coexistent with AD were also stained. With the exception of vessels in two of the five cases, AP was not detected in age-matched controls. Our observations indicate AP to be a consistent feature of cerebral NFP and amyloid deposits. PMID- 1891065 TI - Expression of alternative isoforms of the neural cell adhesion molecule (NCAM) on normal brain and a variety of brain tumours. AB - A panel of monoclonal antibodies, including a reagent designated ERIC-1, have been characterized as binding to the human neural cell adhesion molecule (NCAM). These monoclonal antibodies bind in a relatively uniform manner to a variety of normal and neoplastic tissues arising from the neuroectoderm. However, multiple forms of the protein are known to arise from the differential splicing of exons within the NCAM gene located on chromosome 11 at q23. On human adult brain, four isoforms of 180, 170, 145 and 120 kDa have been identified. Here, we report the identification of another NCAM isoform of 95 kDa that is apparent on tissues following either N-glycanase or neuraminidase treatment to remove carbohydrate and sialic acid residues from the molecule respectively. NCAM expression is further complicated by differential post-translational modification of the molecule which is developmentally regulated. In general, fetal NCAM is more heavily polysialylated than the adult forms of the molecule. Human fetal brain has been shown to express the heavily sialylated embryonic form of NCAM, but following neuraminidase digestion, a similar pattern of NCAM expression is seen to that in adult brain. A variety of human brain tumours examined also show different patterns of NCAM expression, despite their uniform staining with monoclonal antibodies. The significance of these observations for designing new molecular and immunological approaches to the diagnosis of a variety of primary tumours is reviewed. PMID- 1891066 TI - B and T lymphocytes are affected in lysosomal disorders--an immunoelectron microscopic study. AB - Circulating lymphocytes of four patients with mucopolysaccharidoses II and IIIA, four patients with juvenile neuronal ceroid-lipofuscinosis, one patient each with glycogenosis type II, infantile neuronal ceroid-lipofuscinosis, and Gaucher disease were classified by immunoelectron microscopy as B or T lymphocytes. Disease-specific lysosomal inclusions as well as non-specific lysosomal organelles, especially Gall bodies were identified in B and T lymphocytes. These non-quantitative studies indicate that both B and T lymphocytes participate in the lysosomal storage process. PMID- 1891067 TI - Respiratory burst activity in brain macrophages: a flow cytometric study on cultured rat microglia. AB - A new flow cytometric method for the investigation of the respiratory burst of macrophages/microglia isolated from neonatal rat brain has been established. Respiratory burst activity was measured quantitatively in single viable cells by the intracellular oxidation of non-fluorescent dihydrorhodamine 123 (DHR) to fluorescent rhodamine 123. Cultured microglia exhibited high spontaneous respiratory burst activity already before stimulation. After maximal stimulation with phorbol myristate acetate, DHR oxidation rose by 40-95%. The respiratory burst activity in resident or inflammatory, i.e. thioglycolate elicited, peritoneal macrophages was significantly lower than in cultured brain macrophages suggesting a high potential of microglia for oxidative tissue destruction. PMID- 1891068 TI - Decontamination of Creutzfeldt-Jakob disease agent: current strategies. PMID- 1891069 TI - Current bibliographies of neuropeptides prepared by the University of Sheffield Biomedical Information Service. PMID- 1891070 TI - Blockade of neuropeptide Y-induced potentiation of noradrenaline-evoked vasoconstriction by D-myo-inositol-1.2.6-trisphosphate (PP56) in rabbit femoral arteries. AB - Neuropeptide Y (NPY) potentiates noradrenaline (NA)-evoked constriction of circular segments of the rabbit femoral artery. The potentiation occurs exclusively in the lower concentration-range of the agonist NA (10(-8)-3 x 10(-7) M) without any change in maximum contractile effect. NPY per se is without contractile effect in the rabbit femoral artery. The recently developed substance, D-myo-inositol-1.2.6-trisphosphate (PP56), which is an isomer of inositol-1.4.5-trisphosphate, is without effect per se on the rabbit femoral artery, nor does it affect NA-induced contractions. However, it was found to completely antagonize NPY-induced potentiation of the NA concentration-response curve. PMID- 1891071 TI - Could dietary proteins serve as cyclo(His-Pro) precursors? AB - Cyclic dipeptides or diketopiperazines are readily generated during in vitro hydrolysis of proteins and polypeptides. This led us to examine whether cyclo(His Pro) (CHP), a diketopiperazine containing histidine and proline, could be formed in vivo from dietary proteins. The data presented here show that at least in rat, neither urinary nor plasma concentration of CHP is elevated by consumption of a diet rich in proteins. Several dietary supplements derived from casein and/or soy protein hydrolysates, however, contain high levels of CHP-LI. Oral intake of one such supplement led to a sharp increase in the plasma level of CHP-LI. PMID- 1891072 TI - Nicotine-induced alterations in peripheral tissue concentrations of native and cryptic Met- and Leu-enkephalin. AB - This study examined the peripheral tissue distribution of native and cryptic Met- and Leu-enkephalin, and regulation of tissue enkephalins by nicotine. Met- and Leu-enkephalin concentrations showed widespread variation in tissue concentration and degree of processing. HPLC characterization of homogenate of spleen revealed that both native and cryptic immunoreactive Met-enkephalin are comprised of two peaks, one representing authentic Met-enkephalin pentapeptide and the other its sulfoxide. Subacute repeated administration of nicotine 0.1 mg/kg ip, six times at 30 min intervals, increased native Met- and Leu-enkephalin in adrenal medulla without affecting cryptic Met- and Leu-enkephalin concentrations, consistent with increased processing of larger peptides to Met- and Leu-enkephalin. Subacute nicotine decreased splenic concentrations of native and cryptic Met-enkephalin and native Leu-enkephalin, consistent with increased release of Met- and Leu enkephalin from spleen and decreased synthesis of proenkephalin A or inadequate processing of larger peptides to enkephalin pentapeptides in spleen to compensate for the increased release during this period. HPLC characterization revealed that nicotine-induced decrease in native Met-enkephalin in spleen resulted from reductions in both pentapeptide and its sulfoxide. Nicotine also increased native Met-enkephalin in jejunum, decreased cryptic Met-enkephalin in heart atrium, increased native Leu-enkephalin in anterior pituitary and decreased cryptic Leu enkephalin in jejunum. Nicotine may produce some of its effects through alterations in release of enkephalins from peripheral tissues. PMID- 1891073 TI - Selective attenuation of cocaine-induced stereotyped behaviour by oxytocin: putative role of basal forebrain target sites. AB - The effects of oxytocin (OXT), arginine- and lysine-vasopressin (AVP and LVP) and an OXT-receptor antagonist on cocaine-induced sniffing behaviour were investigated in rats. OXT, but not AVP or LVP injected subcutaneously (s.c.) attenuated cocaine-induced sniffing. The effect of OXT (s.c.) was inhibited by an OXT-receptor antagonist administered intracerebroventricularly (i.c.v.). I.c.v. administration of different doses of OXT in nanogram quantities caused a dose dependent attenuation of cocaine-induced sniffing. Local cerebral microinjection of OXT into the accumbens nucleus and olfactory tubercle but not into the olfactory nucleus, central amygdaloid nucleus or caudate nucleus, inhibited the cocaine-induced sniffing behaviour. These results demonstrate that OXT selectively attenuates the cocaine-induced stereotyped behaviour through basal forebrain target sites. PMID- 1891074 TI - Central administration of Lys-D-Pro-Thr, an interleukin-1 beta 193-195 analogue, stimulates feeding in rats. AB - We determined the effect on feeding of Lys-D-Pro-Thr (LDPT), an interleukin-1 beta 193-195 analogue which antagonizes the analgesic effects of interleukin-1 beta. Intracerebroventricular administration of 2 micrograms/rat LDPT increased food consumption at the 0-1 h time period, although food intake was reduced by LDPT at the 1-2 h time period. There was no effect on colonic temperature 1 h later. Subcutaneously injected LDPT (2 micrograms/rat) failed to increase food intake for 1 h. These data suggest that brain interleukin-1 beta may have a physiological role in feeding suppression. PMID- 1891075 TI - Section of geriatric neurology. PMID- 1891076 TI - The decline of mortality due to stroke: a competitive and deterministic perspective. AB - Although stroke mortality has been declining since the first part of this century, the rate of decline increased sharply during the early 1970s. The basis for the fall in stroke mortality is often attributed to effective management of risk factors, particularly hypertension. However, some investigators have questioned whether risk factor reduction alone can adequately account for the magnitude of the recent decline in stroke mortality. When viewed from the perspective of competitive and deterministic mortality dynamics, the major force decreasing stroke mortality is the decreasing deterministic competitiveness of stroke and the increasing deterministic competitiveness of various malignant neoplasms and degenerative diseases as causes of mortality. These reciprocal trends are a natural consequence of the competitive deterministic mortality dynamics which describe these diseases in an environment that is becoming more conducive to human survival. The competitive nature of human mortality makes drawing etiopathogenic conclusions based upon single disease mortality data hazardous. PMID- 1891077 TI - Technology assessment revisited: does positron emission tomography have proven clinical efficacy? PMID- 1891078 TI - 4-Aminopyridine in multiple sclerosis: prolonged administration. AB - In an earlier study, we demonstrated efficacy of single oral doses of 4 aminopyridine (4-AP) in improving motor and visual signs in multiple sclerosis (MS) patients for a mean of 4.97 hours. We attempted to determine whether efficacy could safely be prolonged using multiple daily doses over several days by administering 7.5 to 52.5 mg 4-AP to 17 temperature-sensitive MS patients in one to three daily doses at 3- to 4-hour intervals over 1 to 5 days in a double blind study. Nine of these patients were also tested with identically appearing placebo. Thirteen of the 17 patients (76%) given 4-AP showed clinically important motor and visual improvements compared with three of nine in the placebo group. Average peak improvement scores were 0.40 for 4-AP and 0.12 for placebo. Seventy percent of the daily 4-AP improvements lasted 7 to 10 hours. The improvements for two consecutive doses of 4-AP lasted a mean of 7.07 hours (83% of the average 8.53-hour treatment-observation period) compared with 2.36 hours for placebo (26% of the average 9.06-hour treatment-observation period). No serious side effects occurred. 4-AP is a promising drug for the symptomatic treatment of MS. PMID- 1891079 TI - The effect of high-dose steroids on MRI gadolinium enhancement in acute demyelinating lesions. AB - Gadolinium (Gd) enhancement of brain lesions by MRI is a marker of active blood brain barrier damage secondary to an inflammatory process. We studied the effects of high-dose (1,000 mg/d) intravenous (IV) methylprednisolone (Mp) for 4 to 8 days on Gd-enhancing lesions in seven patients with acute demyelinating diseases and compared pretreatment brain MRIs with studies obtained 1 to 4 days after treatment. Five patients had complete suppression, and two had significant suppression of Gd enhancement following treatment. In addition, six of seven patients had Gd-enhancing lesions that explained their clinical signs; in five of six of these patients, suppression of the Gd-enhanced lesions temporally correlated with clinical improvement. Thus, short courses of high-dose IV Mp suppress Gd enhancement in acute demyelinating lesions, and this correlates with clinical improvement. PMID- 1891080 TI - HTLV-I-associated myelopathy/tropical spastic paraparesis in the United States. AB - HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is endemic in the Caribbean basin and Japan. Because of the close proximity of the United States to the Caribbean and the presence of HTLV-I-seropositive persons in the United States, we sought reports of patients who were HTLV-I seropositive and had a slowly progressive myelopathy. Over a 2-year period, there were 25 patients reported, 19 of whom were black and 12 of whom had been born in the United States. All patients except two had become symptomatic while living in the United States. Six patients had no apparent risk factor for acquiring HTLV-I. These data demonstrate that HAM/TSP is occurring in the United States and that the diagnosis of HAM/TSP should be considered in patients with a slowly progressive myelopathy regardless of risk factors for acquiring HTLV-I. PMID- 1891081 TI - Occurrence of stroke associated with use/abuse of drugs. AB - Ischemic and hemorrhagic stroke frequently occur in temporal association with use or abuse of illicit and over-the-counter (OTC) sympathomimetic drugs. However, little information is available on the proportion of strokes associated with use/abuse of drugs in specific hospital populations. Between September 1, 1988, and August 1, 1989, 167 of 178 stroke patients entered into the Maryland Stroke Data Bank were asked for a history of drug use or abuse. Information was incomplete in 51 of 167 (31%) patients due to neurologic deficit or lack of inquiry. Eleven of the remaining 116 cases (9.5%) were historically associated with drug use. Age range was 25 to 56 years (mean, 41 years). Stroke associated with drug use occurred in four of 62 (6%) cerebral infarcts, two of 28 (7%) intracerebral hemorrhages, and five of 26 (19%) subarachnoid hemorrhages (p = ns). Drugs included cocaine in five (45%), OTC sympathomimetics in three (27%), phencyclidine in two (18%), and heroin in one (9%). PMID- 1891082 TI - Autosomal recessive distal dystrophy. AB - We describe five new cases of autosomal recessive distal dystrophy (Miyoshi myopathy) and emphasize the distinctive clinical and laboratory features of this unusual muscular dystrophy. Symptoms began at age 15 to 25, the gastrocnemius muscles were selectively involved, and creatine kinase was elevated more than 10 times normal. The EMG showed abundant brief motor units with numerous fibrillations. Dystrophic features without vacuoles were best seen in the biceps femoris muscle. Asymptomatic creatine kinase elevation was present years prior to the development of weakness. The disorder appears to be inherited in an autosomal recessive pattern. Miyoshi myopathy can be distinguished from other distal muscular dystrophies. We propose a new classification for the distal muscular dystrophies. PMID- 1891083 TI - Inherited protein C deficiency and nonhemorrhagic arterial stroke in young adults. AB - Out of a consecutive series of 50 young people less than 45 years old with nonhemorrhagic arterial stroke, three patients had inherited protein C deficiency. CT revealed hypodense areas consistent with the clinical picture, and angiography showed occlusion of some intracranial arterial vessels. Other possible associated causes of stroke were ruled out. One patient had a transient ischemic attack and a peripheral venous thrombosis prior to the actual stroke, whereas the others were completely asymptomatic, as were relatives with the same deficiency. We suggest determining protein C in ischemic stroke of all young adults, especially when major risk factors are excluded. PMID- 1891085 TI - Globoid cell leukodystrophy: a family with both late-infantile and adult type. AB - We present a patient with adult-onset globoid cell leukodystrophy (GBL) who had almost complete deficiency of galactosylceramide beta-galactosidase. A brother of the index patient deteriorated neurologically and died at the age of 4, probably from the late-infantile form of the disease. In this family, two clinical types of GBL are probably different expressions of an identical genotype. PMID- 1891084 TI - Frontal lobe degeneration: clinical, neuropsychological, and SPECT characteristics. AB - The clinical, neuropsychological, and cerebral blood flow characteristics of eight patients with frontal lobe degeneration (FLD) were studied. Social withdrawal and behavioral disinhibition were the earliest and most common clinical presentations, and psychiatric symptoms typically preceded the onset of dementia by several years. Neuropsychological testing showed selective impairment of frontal and memory tasks with relative sparing of attention, language, and visuospatial skills. Single-photon emission computerized tomography demonstrated frontal and temporal hypoperfusion with relative sparing of parietal and occipital blood flow. Previous studies suggest that the neuropathologic findings in patients with FLD are varied; some demonstrate frontal gliosis, neuronal loss, and Pick bodies while others show only gliosis and neuronal loss. PMID- 1891086 TI - The Libyan Creutzfeldt-Jakob disease focus in Israel: an epidemiologic evaluation. AB - In a country-wide study of Creutzfeldt-Jakob disease (CJD) in Israel, we diagnosed 114 cases, among them 49 Libyan-born, with onset of their disease during the years 1963-1987. After age adjustment, the mean annual incidence rate per million population was 43 among Libyan-born and 0.9 in the rest of the population. Among Jews born in Egypt and Tunisia, neighboring countries of Libya, the adjusted rates were higher than in the other Israelis (3.5 and 2.3 per million, respectively). Among Libyan Jews, there was no association between incidence rate of CJD and age at immigration, ie, duration of exposure to hypothetical infectious factor in Libya. The percent of familial cases among Libyan Jews (41 to 47%) is one of the highest ever published. Genetic factors seem to be important for the high incidence of CJD among Libyan Jews. PMID- 1891087 TI - Do Creutzfeldt-Jakob disease patients of Jewish Libyan origin have unique clinical features? AB - A focus of Creutzfeldt-Jakob disease is present in Israel among Jews born in Libya. The present study examines the clinical features in this particular group of patients. In a country-wide study of Creutzfeldt-Jakob disease, we identified 114 patients; 49 were Libyan immigrants, and 65 (three of whom had Libyan ancestors) were born in other countries. The clinical presentation and evolution of the disease is very similar in patients born in Libya and others without Libyan ancestors, but it tends to be more classical in the Libyan patients, with higher frequency of myoclonic jerks and periodic EEG and a progressive course of shorter duration. The Libyan patients tend to complain more often of headache, which is most probably an ethnic expression for depression and loss of concentration. There was no difference between the familial and nonfamilial cases. PMID- 1891088 TI - Clinical risk factors for Alzheimer's disease: a population-based case-control study. AB - Using information on clinical risk factors provided through the medical record linkage system of the Rochester Epidemiology Project, we conducted a population based case-control study of Alzheimer's disease (AD). During the period 1960 to 1974, we identified 415 newly diagnosed cases of AD among residents of Rochester, Minnesota, and matched one community control to each case based on age, sex, and duration of community medical record. We estimated odds ratios using conditional logistic regression for several potential clinical risk factors of AD. Among more than 20 clinical risk factors that were evaluated, the only statistically significant findings were for episodic depression, personality disorder, and hypertension. PMID- 1891089 TI - Significance of CSF immunoglobulins in monitoring neurologic disease activity in Behcet's disease. AB - We examined the intrathecal production of immunoglobulins (Ig) G, A, and M in 16 patients with Behcet's disease, 13 of whom have CNS involvement, and in 40 neurologic controls. Oligoclonal IgA and IgM bands were mainly detected in CSF samples from patients with active neuro-Behcet's disease and were documented to disappear when neurologic manifestations remit. Oligoclonal IgG bands, however, were not related to disease activity and were also found in some neurologic controls. High immunoglobulin index values were detected in both active and quiescent diseases and were high in some patients with impaired blood-CSF barriers. The study presented here demonstrates that CSF oligoclonal IgA and IgM may be helpful in monitoring CNS disease activity in neuro-Behcet's and could be useful in understanding the pathogenesis of this disease. PMID- 1891090 TI - Clinical characteristics of transient ischemic attacks in black patients. AB - We analyzed the clinical, CT, and angiographic findings in 50 black patients with carotid transient ischemic attacks (TIAs). Thirty-two percent had TIAs lasting less than 1 hour, 26% had TIAs lasting 1 to 6 hours, and 42% had TIAs lasting 6 to 24 hours. Fifty-two percent of TIA patients had CT evidence of cerebral infarction despite complete clinical recovery. CT was abnormal in two of 16 (13%) patients with TIAs lasting less than 1 hour; however, CT was abnormal in 24 of 34 (70%) patients with TIAs lasting longer than 1 hour. Angiographic findings of extracranial carotid disease appropriate to TIA symptoms were present in 12 (24%) patients. Two patients in whom the TIA episode lasted less than 1 hour later had clinical cerebral infarction, whereas 20 patients with longer-duration TIAs developed ischemic stroke within 4 months. Of these black TIA patients, 22 (44%) developed clinical cerebral infarction. PMID- 1891091 TI - Clinicopathologic observations in essential tremor: report of six cases. AB - Essential tremor (ET) is the most common pathologic tremor, but only eight cases have been studied pathologically. We report detailed clinical and neuropathologic studies of six additional patients. We did not find any neuropathologic lesions that might be specific for ET. Moreover, there were no abnormalities of the substantia nigra consistent with Parkinson's disease. The neuropathologic substrate of ET remains unknown. PMID- 1891092 TI - Spike voltage topography identifies two types of frontotemporal epileptic foci. AB - We characterized voltage topography of frontotemporal EEG spikes in 24 patients with complex partial seizures and identified two distinct patterns. "Type 1" spikes possessed a "dipolar" field with a negative region over the inferolateral temporal scalp and a positive region over the contralateral, centroparietal scalp. "Type 2" spikes showed only a broad, frontotemporal negative field. One or the other spike type predominated in all but two patients. Correlations with clinical data and intracranial EEG suggest that type 2 spikes arise from temporal or frontal neocortex, while type 1 spikes involve mesial temporal structures as well as lateral cortex. PMID- 1891093 TI - The occurrence of epilepsy and febrile seizures in Virginian and Norwegian twins. AB - Twin studies provide an efficient method for examining the importance of genetic and environmental factors in the etiology of disorders such as epilepsy. Population-based twin registries are especially valuable for studies of this type since effects of reporting and self-selection biases on the resulting data are minimized. Among 14,352 twin pairs contained in the Virginia and Norwegian twin panels for whom questionnaire information was available, there was a history of epilepsy in one or both members of 286 pairs; febrile seizures were reported in 257 pairs. Analyses of questionnaire data revealed no significant differences in concordance rates between Virginian and Norwegian twins for either epilepsy or febrile seizures. Probandwise concordance rates for epilepsy were 0.19 in monozygotic twins and 0.07 in dizygotic twins. Analogous rates for febrile seizures were 0.33 (monozygotic) and 0.11 (dizygotic). These results provide further evidence that genetic factors do have a role in the expression of epilepsy and febrile seizures. PMID- 1891094 TI - Visual sensitivity to motion: age-related changes and deficits in senile dementia of the Alzheimer type. AB - To determine whether motion sensitivity varies with age, we measured motion discrimination in visual normals 25 to 80 years of age and found that motion thresholds increased linearly with age and were approximately two times higher in those 70 to 80 years old than in participants under thirty. This increase was not attributable to pupil size or retinal image distortion, but probably reflects neurodegeneration in the primary visual pathway. We compared the motion sensitivity of patients with senile dementia of the Alzheimer type (SDAT) with results from a subset of the visual normals of similar age. In SDAT patients, there were significant threshold elevations, which were more pronounced in the patients with more severe dementia. These findings confirm previous reports of visual system involvement in SDAT and indicate motion testing may reveal preclinical visual system involvement in SDAT. PMID- 1891095 TI - Hemispheric threshold differences for motor evoked potentials produced by magnetic coil stimulation. AB - A brief monophasic pulse through an electromagnetic coil preferentially activates motor pathways of each hemisphere, depending on the direction of coil current flow. Using the preferred direction for each hemisphere, the minimum stimulus intensity (threshold) that evoked compound muscle action potentials in the contralateral abductor digiti minimi (ADM) muscle was significantly less for the left hemisphere than the right. Threshold for biceps on each side was significantly higher than ADM, but there was no side-to-side difference. Assessing handedness using a standard handedness index, those who had less tendency to use the right hand for everyday tasks had greater differences between hemispheres for ADM thresholds. The lower threshold of the left-hemisphere projection to hand muscles is probably related to the asymmetry of corticomotoneuronal monosynaptic connections; a greater number project to the motor neuron pool of the right- than left-hand muscles. PMID- 1891096 TI - Alteration of renal carnitine metabolism by anticonvulsant treatment. AB - We administered therapeutic doses of valproic acid (VPA), carbamazepine (CBZ), phenytoin (PHT), and phenobarbital (PHB) to mice for 7 days, and 8 hours after the final dose we measured the concentrations of carnitine in serum, liver, kidney, skeletal muscle, and heart, and in the 7 days' accumulated urine. The results for serum and urine show that VPA induced a significant increase in renal clearance of acylcarnitine without affecting that of free carnitine, whereas CBZ, PHT, and PHB significant increased clearance of free carnitine but not that of acylcarnitine. Thus, VPA appears to reduce tubular resorption of acylcarnitine, and CBZ, PHT, and PHB appear to reduce tubular resorption of free carnitine. PMID- 1891097 TI - Parkinson's disease rigidity: magnetic motor evoked potentials in a small hand muscle. AB - We studied the EMG potentials evoked in the bilateral first dorsal interosseus muscle by electromagnetic stimulation of the corticomotoneuronal descending system in 10 Parkinson's disease patients and in 10 age- and sex-matched normal controls. We selected patients who did not have tremor but had predominant rigidity with asymmetric body involvement. On the rigid side of the PD patients, the threshold to cortical stimulation was lower than on the contralateral side or than normal values. On average, patients had normal central conduction times, but their motor evoked potentials (MEPs) on the rigid side were larger than those of controls when the cortical stimulus was at rest or during slight tonic contraction of the target muscle. In the latter condition, a silent period shorter than that of controls followed MEPs, whereas the peripheral silent period following ulnar nerve stimulation at the wrist was prolonged. Alpha motor neuron excitability, tested by the F-wave method, was enhanced on the rigid side at rest. In rigidity, spinal motor nuclei may be more responsive than normal to descending inputs from motor cortex, or the entire corticomotoneuron system may prove hyperexcitable under given conditions. PMID- 1891098 TI - Chronic morphine therapy for cancer pain: plasma and cerebrospinal fluid morphine and morphine-6-glucuronide concentrations. AB - Morphine-6-glucuronide (M-6-G) is an active metabolite that may contribute to the clinical effects produced by systemic administration of morphine. To help clarify the extent to which M-6-G may cross the blood-brain barrier and exert effects, we employed high-performance liquid chromatography with electrochemical detection to measure the concentrations of M-6-G and morphine in the plasma and either ventricular (three patients) or lumbar (eight patients) CSF of cancer patients receiving chronic morphine therapy. The mean ratio of morphine in ventricular CSF:morphine in plasma was 0.71; the same ratio for M-6-G was only 0.077. The average molar ratio of M-6-G: morphine in ventricular CSF was 0.207, and the average molar ratio in plasma was 1.89. Although sampling problems render the lumbar CSF results less reliable, they were very similar. Thus, plasma contained approximately twice as much M-6-G as morphine, whereas CSF contained only one fifth to one-third as much. These data confirm that M-6-G in plasma is distributed into CSF, but to a far lesser extent than morphine. They help explain animal data demonstrating much higher potency of M-6-G on administration into CSF than systemic administration and indicate that the degree to which M-6-G contributes to morphine effects in humans remains an unresolved question. PMID- 1891099 TI - Baroreflexes in patients with diabetes mellitus. AB - We evaluated baroreflexes in 58 diabetic and 15 control subjects by determining the latency of response between the end of a Valsalva maneuver (VM) and points on the resultant blood pressure and heart rate (HR) response curves. Prolonged latencies indicative of sympathetic dysfunction were demonstrated in 44% to 88% of diabetic subjects. The results challenge the view that sympathetic dysfunction cannot be detected before parasympathetic abnormalities are manifest. Baroreflex latencies reflected sympathetic dysfunction early in the course of diabetes, sometimes in patients with normal HR responses to deep breathing and to a VM. PMID- 1891100 TI - Fetal akinesia deformation sequence (Pena-Shokeir phenotype) associated with acquired intrauterine brain damage. AB - An infant with Pena-Shokeir phenotype was born to a cocaine-using mother. The pathologic findings included polyhydramnios, facial anomalies, arthrogryposis, camptodactyly, pulmonary hypoplasia, and tetralogy of Fallot. The neuropathologic findings were diffuse brainstem and spinal cord neuronal degeneration and focal cerebral infarction, consistent with acquired intrauterine ischemic damage. PMID- 1891101 TI - Motor initiation versus execution in normal and Parkinson's disease subjects. AB - We studied motor initiation and execution using wrist extension movements to changing target locations in eight normal subjects and nine Parkinson's disease (PD) patients before and after medications. Late changes resulted in double trajectories, indicating commitment to the initial target acquisition program followed by a correcting movement. There was compensation for earlier changes, even after onset of agonist muscle activity, resulting in a single trajectory, implying that the original trajectory had not yet been specified. However, movements were slowed in PD patients implying an abnormality in the content of the target acquisition program but not in the timing of its specification. In PD patients, the timing of the second movement onset correlated best with the timing of target location change and did not depend on initial movement completion. Thus, PD patients were able to program the second movement while the first movement was under way. PMID- 1891102 TI - Reaction time and movement velocity abnormalities in Parkinson's disease under different task conditions. AB - We examined reaction times, movement velocities, and the associated agonist and antagonist muscle behaviors in nine Parkinson's disease (PD) patients and eight normal subjects before and after medications, using a wrist extension task to changing locations of a visual target. Targets changing 500 msec before an auditory "go" signal act as a preparatory cue, while targets changing at the time of the go signal provide a combined auditory and visual stimulus. Late target changes allowed examination of (1) reaction times during an ongoing movement, and (2) movement in the presence and absence of visual targets. PD prolonged the time from the onset agonist electromyographic activity and reduction of antagonist activity to movement onset. Both were shortened by preparatory cues and combined visual and auditory go signals. PD slowed movement only in a subset of trials in which there was movement to a displayed target. PMID- 1891103 TI - Inflammation at the neuromuscular junction in myasthenia gravis. AB - To better define the pathogenic mechanisms in the antibody-mediated autoimmune disease myasthenia gravis (MG), we analyzed the morphology and electrophysiology of the neuromuscular junction in anconeus muscle biopsy specimens from eight patients with MG and seven control subjects. There were inflammatory cells at the neuromuscular junction in seven of the eight biopsies from MG patients. The endplate index (length of the postsynaptic membrane divided by the length of the apposed presynaptic membrane) was abnormally reduced in all the MG patients, and fiber type grouping, suggestive of reinnervation, was present in six of the eight MG patients. Intracellular recording revealed diminished amplitude of miniature endplate potentials and miniature endplate currents in the MG patients compared with the controls. The time constant of decay of miniature endplate currents did not differ from that of controls, suggesting no change in mean channel open time of the acetylcholine receptor. The endplate receptor sensitivity to iontophoretically applied acetylcholine was also decreased in MG patients compared with controls. The quantal content of neurally evoked endplate potentials was reduced in six of the eight MG patients, demonstrating abnormal presynaptic function as well. The presence of inflammatory cells at the neuromuscular junctions of limb muscles in MG reconciles an apparent disparity between the animal model of MG, experimental autoimmune myasthenia gravis, and the human disease. This study also demonstrates a frequent presynaptic component to the abnormal neuromuscular transmission in MG. PMID- 1891104 TI - Plasticity of central motor pathways in children with hemiplegic cerebral palsy. AB - To obtain neurophysiologic evidence for a reorganization of central motor pathways in children who had suffered a cerebral lesion at birth, we performed cross-correlation analyses of multiunit EMG recordings obtained from children with hemiplegic cerebral palsy and marked mirror movements. We found that the motoneuron pools of homologous left and right hand muscles received common synaptic input from abnormally branched presynaptic axons. The results of electromagnetic brain stimulation, cutaneomuscular, and tendon reflex testing suggested that these common inputs are provided by abnormally branched corticospinal tract fibers whose origin is the undamaged motor cortex. PMID- 1891105 TI - The prognostic value of postoperative seizures following epilepsy surgery. AB - Among 55 patients undergoing temporal lobectomy for refractory epilepsy, patients with seizures in the week following surgery had a poor long-term, seizure-free outcome compared with patients without seizures. Outcome for patients with single seizures or seizures restricted to the first postoperative day seemed favorable compared with patients with multiple or later seizures. Seizure type and similarity to preoperative events did not predict outcome. PMID- 1891106 TI - Presence of human T lymphotropic virus type I in two patients with progressive myelopathy in Puerto Rico. AB - Two patients from Puerto Rico with progressive paraparesis had serum positive for human T lymphotropic virus type I (HTLV-I) antibodies by ELISA and Western blot, and one patient had HTLV-I antibodies in CSF by the ELISA method. Although the Caribbean basin is considered to be an endemic area for tropical spastic paraparesis, this is the first report of the isolation of HTLV-I antibodies in the serum and CSF of patients with chronic myelopathies in Puerto Rico. PMID- 1891107 TI - Hemidystonia due to a contralateral parieto-occipital metastasis: disappearance after removal of the mass lesion. AB - A patient presented with left-sided hemidystonia. CT revealed a contralateral parieto-occipital mass lesion compressing the basal ganglia, which were spared by the mass. After microsurgical resection of the tumor, which was verified histologically as a metastasis of a large-cell anaplastic carcinoma, the movement disorder dissolved completely. PMID- 1891108 TI - Subarachnoid hemorrhage in sickle cell anemia: evaluation using parenchymal and vascular magnetic resonance imaging. PMID- 1891109 TI - Intravenous immunoglobulin and pyridoxine-dependent seizures. PMID- 1891110 TI - Spontaneous disappearance of an arachnoid cyst in the middle intracranial fossa. PMID- 1891111 TI - Hyperintensity in the globus pallidus on T1-weighted and inversion-recovery MRI: a possible marker of advanced liver disease. PMID- 1891112 TI - CNS lupus. PMID- 1891113 TI - Absence status triggered by pallid syncopal spells. PMID- 1891114 TI - Sarcoid myelopathy. PMID- 1891115 TI - Axonal Guillain-Barre. PMID- 1891116 TI - Eye muscles and myasthenia. PMID- 1891117 TI - Thoughts on conventions. PMID- 1891118 TI - A question of semantics. PMID- 1891119 TI - Dimensionless? PMID- 1891120 TI - AIDS: advocacy and activism. PMID- 1891121 TI - A nurse in the sand. Letters home. PMID- 1891122 TI - Midwifery education and nursing: curricular revolution or civil war? AB - Midwives throughout the nation are seeking an alternative path to midwifery certification known as direct entry. Muzio analyzes the arguments against direct entry, and makes a challenging proposal that not everyone will like. PMID- 1891123 TI - Joint venture arrangement for RN to BSN. A model of synergy between academia and service. AB - The joint venture between or among educational and practice institutions is fast becoming the norm in nursing education and practice. Authors Bargagliotti, Jones, Trygstad, Hayward, Crow, and Bower, describe one such program enabling RNs to pursue the BSN degree. PMID- 1891125 TI - A surgeon defends himself in a malpractice trial. AB - The author presents a case of disc escape without strut fracture in a Bjork Shiley tilting-disc aortic valve. Two years after the patient's death, the surgeon, the valve company, the hospital, and others were sued. The surgeon, a first-year law student, represented himself, pro se, at trial. PMID- 1891127 TI - Simulation of breast carcinoma. AB - In Radiology Rounds, the authors presents a case history, mammogram, and discussion of causes of diseases simulating carcinoma of the breast. The patient is a 59-year-old female. The diagnosis is edema of the breast secondary to congestive heart failure, mimicking carcinoma. PMID- 1891126 TI - Part II: Basic approach to health screening. AB - It is hoped that practicing physicians no longer will give knee jerk reactions to the variety of national screening recommendations. Screening criteria that need to be fulfilled include characteristics of the disease, characteristics of the test, and characteristics of the population to be screened. In the day-to-day practice of medicine, six key questions regarding the applications of screening recommendations to individual patients have been developed. These include the qualifying questions regarding the patient's age, frequency of testing, cost effectiveness of testing, realistic practice for the physician, appropriate setting, and applicability to the patient in question. In the future, research in the area of screening needs to focus on the demographics of a greater variety of asymptomatic population groups, the effectiveness of current recommendations and guidelines, and the development of new, effective screening tests. PMID- 1891128 TI - Special correspondence: vision standards. AB - Physicians and ophthalmologists must know the vision standards for driving motor vehicles, as they are requested by patients to complete the necessary forms to obtain a restricted license. Physicians also should know why some standards are not in the best interests of their patients. PMID- 1891124 TI - Special report: video-endoscopic thoracic surgery. AB - Since the advent of video optics, with the projection of images on a screen, a new option has been added to the armamentarium of the thoracic surgeon: video endoscopic thoracic surgery. A case report of a 33-year-old woman demonstrates the successful new procedure. PMID- 1891129 TI - PRO changes under the fourth scope of work for Medicare. AB - The Fourth Scope of Work for the Medicare Program will become effective on December 1, 1991. This program will change the methodology utilized by peer review organizations throughout the country in performing federally mandated review of the medical care provided to Medicare patients. PMID- 1891130 TI - The biosynthesis of shikimate metabolites. PMID- 1891131 TI - The extent of cervical screening in New Zealand women. AB - To estimate the extent of cervical screening coverage of New Zealand women, a national survey of 1000 randomly selected women with a supplement of 200 Maori women was carried out by the National Research Bureau in August 1990 for the Department of Health. The results indicate a high level of screening in women aged 20-64 and improvements in coverage over the last three years, probably in response to the Cartwright inquiry. Overall, 77% of women reported having had a smear test within the previous three years and after adjustment for hysterectomy, this proportion increased to 82%. Screening coverage, however, was unevenly spread according to ethnic group, age and household income. Only 15% of European women reported no smear test in the last three years compared with 27% of Maori and Pacific Island women. The likelihood of having had a smear test in the last three years increased with increasing income. The survey confirms a high level of very frequent screening throughout New Zealand (2.4 smear tests per woman in the previous three years); the most frequent screening occurred in women 20-24 years of age (2.9 smears). Because an organised national screening programme has the potential to maintain and extend screening coverage to all age and ethnic groups, as well as reduce the number of unnecessary smears, it is likely to be more cost effective than the current screening practice. PMID- 1891132 TI - Long term complications following renal transplantation. AB - The long term complications of renal transplantation were assessed in 36 patients who had lived for 10 or more years with a functioning renal transplant. Thirty three patients were alive with a mean plasma creatinine of 0.13 mmol/L (SD 0.07). A 62 year old women died from a myocardial infarction 11 years after transplantation and two women developed chronic rejection and returned to dialysis after 17 years. Nineteen patients have required antihypertensive therapy, five have suffered ischaemic heart disease and two a cerebrovascular event. Malignancy has developed in 13 patients, with four having two or more organs involved. Skin cancers (9 squamous cell, 4 basal cell) were present in all 13 patients and recurred in six. The other malignancies included carcinoma of cervix (2), cervix and bladder (1) and thyroid (1). Three patients have required parathyroidectomy for autonomous hyperparathyroidism, two splenectomy for hypersplenism, and one bilateral hip replacement for avascular necrosis of the femoral heads. The development of hypertension, vascular disease and malignancy are the most important long term complications after renal transplantation. Strategies must be formulated to reduce the morbidity and mortality from these causes. PMID- 1891133 TI - Urinary catheter toxicity. PMID- 1891134 TI - Waterborne outbreak of Campylobacter jejuni in Christchurch: the importance of a combined epidemiologic and microbiologic investigation. AB - Campylobacter is a common cause of gastroenteritis in New Zealand; however, the source of infection usually remains unknown. Reports of two cases of Campylobacter jejuni enteritis at a camp and convention centre near Christchurch were investigated. Through interviews of persons living at or attending the camp, 42 additional cases were identified. Epidemiologic and microbiologic data strongly suggested the water supply as the source of infection. The combined epidemiologic and microbiologic investigation was useful in quickly defining the magnitude and source of the outbreak, allowing for rapid implementation of control measures. PMID- 1891135 TI - Where have all the doctors gone? Changes in the geographic distribution of general practitioners in New Zealand since 1975 (3): New Zealand and foreign medical graduates compared. AB - Since 1980 new immigration restrictions have reduced the inflow of foreign doctors into New Zealand. These moves not only have changed the composition of the general practitioner workforce, but also have affected its distribution. Data for 1976-87 suggest that market forces have yet to result in New Zealand graduates locating in large numbers in the rural and poorer urban locations that were once the main destinations of FMGs. Also any gains resulting from the targeting of smaller numbers of new FMGs into areas of need have been largely offset by the outmigration of already established foreign doctors. Therefore it is suggested that cuts in immigration are incompatible with market based policies which seek to improve the distribution of general practitioners since limiting the supply of foreign doctors can only slow the pace of any market led redistribution. Seen in this light, recent changes which have limited the inflow of FMGs into New Zealand may well be premature. PMID- 1891136 TI - Prevention of burn injuries to children involving nightwear. AB - The effectiveness of legislative intervention in the New Zealand market for children's nightclothes as an injury prevention strategy has been reassessed by examining those hospital admissions for the period 1980-8 (with emphasis on the 1985-8 period) in which clothing and/or nightclothes were involved. The profiles of the production of children's nightclothes (1977-86) and domestic heating (1984 8) were also examined. Ninety-five cases of burn injury discharges were identified (1985-8), and of those cases involving clothing 42% involved nightwear (49% 1981-4). Some of the 27% unspecified cases may have also involved nightwear (23%, 1981-4). A very strong linear downward trend for nightwear incidents was noted (chi 2 slope = 31.06, p less than 0.001). Forty-eight percent of cases involved children aged 1-6 years, and 68% involved pajamas. Stoves were the main specified ignition agent for nightclothes (36%). Open fires as a form of household heating decreased from 49% to 34% of households (1984-8). Estimated production of nightdresses in New Zealand also decreased (460,000 to 80,000 units, 1973-86). The pronounced decrease in injuries attributable to ignition of children's nightclothes is likely to be the result of mandatory controls on children's nightclothes, increased use of pyjamas, and a steady decrease in use of open fires and portable electric heaters. The typical injury event portrayed to the public of a girl in front of a heater or open fire needs to be corrected. PMID- 1891137 TI - Exposure to fumes in typical New Zealand welding operations. AB - Sixteen welders, welding under typical New Zealand conditions, had ambient air within their welding helmets sampled and analysed for ozone, nitrogen oxides, fluoride, carbon monoxide, aluminium, chromium, iron, nickel, zinc and total dust. Postshift urinary metals were also analysed, and a respiratory questionnaire completed for each welder. Levels above the New Zealand Workplace Exposure Standard (WES) were found for nitrogen dioxide in four welders (two TIG, one MMA and one plasma cutter), and for total chromium in one plasma cutter, who also had a nickel level of 24% of the WES. Dust levels were highest in the plasma cutters, with one reaching 8.67 mg/m3 (WES = 5 mg/m3). Urinary levels however did not indicate excessive short or long term uptake. Where efficient fume extraction was in use, levels of air contaminants were lower than with natural ventilation. Respiratory symptoms were reported by 67% of welders, 38% meeting criteria for chronic bronchitis (relative risk = 2.0). Smoking welders reported more symptoms than nonsmoking welders. PMID- 1891138 TI - General practice prescribing patterns. PMID- 1891139 TI - Fluoride and osteoporosis. PMID- 1891141 TI - Dyslexia--an unhelpful diagnosis. PMID- 1891140 TI - Posttraumatic stress syndrome after war. PMID- 1891142 TI - Today's student--tomorrow's co-worker. PMID- 1891143 TI - Liability issues: patients with psychiatric problems. PMID- 1891144 TI - A systems approach to the management of nursing services, Part VII: Billing system. PMID- 1891145 TI - What you need to know about negotiating contracts. PMID- 1891146 TI - The politics of breast cancer. PMID- 1891147 TI - A cyclical schedule of 10-hour, four-day workweeks. PMID- 1891148 TI - Establishing a 10-hour schedule. PMID- 1891149 TI - Eight- and 12-hour shifts: comparing nurses' behavior patterns. PMID- 1891151 TI - Hiring new graduates and the NCLEX-RN prediction factor. PMID- 1891152 TI - Network leadership and today's nurse. PMID- 1891150 TI - Mother's Hours: "extra" RNs balance the workload. PMID- 1891154 TI - Nursing services: physicians' ratings. PMID- 1891153 TI - National certification for home care RNs. PMID- 1891156 TI - A psychiatric patient classification system. PMID- 1891155 TI - The patient care technician--help in critical times. PMID- 1891157 TI - Career scope--Northeast. PMID- 1891158 TI - HIV testing: where are we? PMID- 1891159 TI - Outpatient surgery: one form sequences efforts. PMID- 1891160 TI - Incinerator study finds problems. PMID- 1891161 TI - Cooled clothing provides comfort and increases worker productivity. PMID- 1891163 TI - Smoke and flame. The experts share their experiences in fire fighting and fire prevention. PMID- 1891162 TI - Labor-supported committees advocate workers' right to understand an MSDS. PMID- 1891164 TI - Hazard analysis, engineered controls prevent chemical process accidents. PMID- 1891165 TI - Positive plan promotes consistent use of safeguards for head, face and eyes. PMID- 1891166 TI - Mitoxantrone as second-line single agent in metastatic breast cancer. AB - Mitoxantrone (MIX), a member of the anthraquinone chemical class, was found to be a potential anticancer agent. It has a similar spectrum of activity as Adriamycin in experimental and human tumors. Thirty-five female patients with metastatic breast cancer, refractory to previous chemotherapy, were treated between 1986 and 1987 with MIX (14 mg/m2 i.v. every 3 weeks); patients with diffuse bone metastases or heavily pretreated patients received 10-12 mg/m2 MIX. All patients were evaluable for response and toxicity. Two patients achieved complete response and 4 partial response, giving an overall response rate of 17%. Median time of response was 5.5 months. The drug was well tolerated. Objective response was obtained mostly in patients with a performance status (Karnofsky scale) of more than 70%, and in those who received more than 12 mg/m2 MIX per course. One patient developed cardiomyopathy, another an acute myocardial infarction, and 3 patients had pathological changes on echocardiography or multigated nuclear angiography. Hematological and gastrointestinal toxicity was tolerable. We found MIX to be a potentially effective second-line treatment with mild toxicity in patients with metastatic breast cancer. PMID- 1891167 TI - Simultaneous cis-platinum and radiotherapy in inoperable or locally advanced squamous cell carcinoma of the head and neck. AB - A synergism between cis-platinum (CDDP) and radiotherapy (RT) has been demonstrated both in culture systems and in clinical studies. On the above basis, we planned, in patients with locally advanced or unresectable squamous cell carcinoma of the head and neck, a concomitant treatment with CDDP 80 mg/m2 i.v. every 3 weeks for three doses (days 1, 21 and 42) and RT in the primary and in the neck nodes bilaterally, for a total dose of 60-70 Gy. Thirty-five untreated patients with poor prognosis unresectable stage II and stages III-IV disease were entered in the study and 32 were evaluable. Complete response (CR) rate was 75% (24/32) with 95% confidence limits from 60 to 90% (+/- 15%): 8 cases (25%) achieved a partial response, for an overall response rate of 100%. A significantly higher CR rate and a longer survival rate was observed in patients with good performance status (PS = 90-100) and stages II-III. The overall estimated 2-year survival is 46%; 59% for patients who obtained a CR versus 0% for those who achieved only a partial response. Overall the treatment was well tolerated and gastrointestinal and hematologic toxicities were the most common side effects. In conclusion, the combination of CDDP plus RT is a very effective and safe treatment and we recommend such an approach in head and neck squamous cell carcinoma, particularly in those patients with good PS and with unresectable stage II or stage III disease. PMID- 1891168 TI - Relative importance of dose, body surface area, sex, and age for 5-fluorouracil clearance. AB - The pharmacokinetics of 5-fluorouracil (FU) has been investigated in 26 cancer patients; 15 of these patients were pretreated with methotrexate (MTX). FU was given by a constant rate intravenous infusion within 10 min, at doses of 320-960 mg/m2. Total plasma clearance, beta-half-life, and steady-state distribution volume were determined with 43 treatments, based on plasma level measurements up to 90 min after the end of the infusion. Average clearance decreased from 1.3 l/min for 320 to 0.7 l/min for 960 mg FU/m2. Multiple linear regression calculations with dose, body surface area, sex, age, and MTX pretreatment as independent variable and clearance as dependent variable confirmed the dependency of clearance on dose and body surface area but also showed that, with equal FU dose per m2, clearance was higher in males than in females, on the average, by 0.22 l/min. There was also suggestive (although not significant) evidence of a (reducing) influence of age on FU clearance. PMID- 1891169 TI - Treatment of 5-fluorouracil-induced stomatitis by allopurinol mouthwashes. AB - 5-Fluorouracil (5-FU) is the most commonly used drug in carcinomas of the gastrointestinal tract. However, stomatitis is one of the limiting side effects. In the present study, 18 patients with gastrointestinal cancer who experienced 5 FU-induced stomatitis in previous cycles used allopurinol mouthwashes in subsequent courses of 5-FU (500 mg of 5-FU/m2/day, i.v., over 2 h for 5 days). The degree of stomatitis diminished in 15 patients (83.3%). Allopurinol mouthwash could be used as a simple and effective method for the reduction of 5-FU-induced oral toxicity. However, further controlled trials are required. PMID- 1891170 TI - Nasopharyngeal carcinoma and lymphoinfiltration. AB - Originally referred to as 'lymphoepithelioma', undifferentiated and poorly differentiated nasopharyngeal carcinoma (NPC) tissues showed intense lymphoinfiltration. In a study of cryosections from 15 NPC tissues, we found that infiltrating lymphoid elements were comprised predominantly of lymphocytes, but plasma cells, follicular dendritic cells, and eosinophils were also commonly seen. Subpopulations of lymphocytes having the same phenotypes tend to aggregate, forming clusters or secondary follicles in stromatous tissues. The tumor areas were mainly infiltrated by T cells. Tumor cells and/or apparently normal epithelium in the paratumorous areas frequently expressed CD21, CD23, CD40 and a B lymphocytes carcinoma cross-reacting antigen (BLCa), all of which are involved in B cell activation and proliferation. CD21 and BLCa were strongly expressed near the surface of both squamous and columnar epithelium by those epithelial cells which are at advanced stage of differentiation, while CD40 was expressed by epithelial cells at earlier stages of differentiation located at or near the basement membrane. CD23 was mainly expressed by columnar cells and basal cells underlying squamous epithelium, but not, or weakly so, by flattened squamous cells or reserve cells underlying columnar epithelium. The large majority of tumor cells expressed CD40 and BLCa. A substantial proportion of them also expressed CD23, but the tumor cells were not reactive for CD21. Despite eosinophilic infiltration, IL-6 was not detected in tumor tissues. IL-1 was, however, detected in abundance in the cytoplasm of follicular dendritic-like cells and in the intercellular spaces in tumor areas and surrounding stromatous tissues. The immunobiology of NPC is discussed in the light of these observations. PMID- 1891172 TI - Cancer patterns at medical centers in Israel and the West Bank. AB - This paper describes the oncological experience on 7,216 patients at two cancer units initiated by one medical team in 1975-1977 at Assaf Harofeh Medical Center in Israel (predominantly serving a Jewish population, 4,671 cases) and at the West Bank Cancer Unit (WBCU), which serves an Arab population (2,545 cases). The two centers have the unique feature of serving two populations residing in close geographic proximity but differing in many cultural and socioeconomic characteristics. Data from the ongoing cancer registries in these two centers are summarized and compare the demographic characteristics of the two study groups, anatomic sites of cancer, methods of diagnosis and extent of disease. The findings at the two centers suggest the presence of different risk factors influencing the site distributions of cancers seen in the two populations served. Among the findings, significantly higher (p less than 0.05) estimated relative risks for cancers of the digestive and urinary-genital systems are observed in each sex group at AHMC than at WBCU. Alternatively, the estimated risk of head and neck cancers was significantly higher among both males and females at WBCU compared with their counterparts at AHMC. Differences in risk were also noted for a number of specific anatomic sites of cancer. PMID- 1891171 TI - Plasma thrombosis-inducing activity in 120 patients with primary lung cancer. AB - One hundred and twenty patients with primary lung cancer were examined for the presence of thrombosis-inducing activity (TIA) in their plasma. TIA was identified in plasma from 16 of 38 patients with stage 3 (42%) and 31 of 65 patients with stage 4 (48%) disease. On the other hand, only 1 of 17 patients with stages 1 and 2 (6%) showed TIA in their plasma. Cell type did not seem to correlate with the presence of plasma TIA, since TIA was identified in plasma from patients with all cell types. Survival of 32 patients with inoperable non small cell lung cancer, all stage 4, was studied. The mean survival time was 7.2 months in the TIA-positive group and 10.3 months in the TIA-negative group. This difference was statistically significant. PMID- 1891173 TI - Familial nonmedullary thyroid cancer. AB - A 5-fold excess risk of nonmedullary thyroid cancer among close relatives of affected patients was detected in a population-based case-control study of thyroid cancer in Connecticut. The 2 familial cases with early onset and multiple foci suggest genetic susceptibility, whereas the 2 cases with late onset may be related to a common environmental exposure. PMID- 1891174 TI - Differences in the kinetics of DNA repair in cancer patients and healthy controls. AB - The time course of DNA repair, using (3H)thymidine uptake as parameter, was measured during 8 h after a single exposure to 2, 8, and 16 UV-C J/m2 in lymphocytes of 8 cancer patients, 1 xeroderma pigmentosum patient and 10 controls. All patients had reduced repair, and all controls normal repair, as calculated 2 h after a single exposure. Six patients reached normal levels with a delay of 2-6 h, whereas 2 patients and the xeroderma pigmentosum patient did not. Although the kinetic curves in controls and patients had a similar form, those for 8 and 16 J/m2 in patients were shifted so that they corresponded to that of 2 J/m2 in controls. Additionally the ability to repair repeated damage (cells irradiated twice or three times at 2-hour intervals with doses of 2 or 8 J/m2) was investigated in 6 patients and in 7 controls. The incorporation values showed significant differences between patients and controls at each dose and time point. Cancer patients tend to repair repeated damage less efficiently than controls. Using these parameters subtle differences between the repair ability of individuals might be identified. Because of the known connection between reduced DNA repair and carcinogenesis, this might help to distinguish cancer-prone individuals. PMID- 1891175 TI - Serum sialyl-Tn antigen levels in patients with digestive cancers. AB - Serum levels of sialyl-Tn antigen (STN) were measured using a one-step radioimmunoassay kit in 257 patients with digestive cancers, 121 patients with benign digestive diseases, and in 64 healthy controls. With 45 U/ml regarded as the cutoff value, the positive rates of serum STN in digestive cancers were as follows: pancreas 40.0%, stomach 28.1, colon and rectum 27.8, biliary tract 25.0, liver 7.1, and esophagus 0%. In benign digestive diseases, the positive rate of STN was low (4.1%). In gastric and colorectal cancers, simultaneous measurements of STN and carcinoembryonic antigen (CEA) revealed that the positive rates of STN, CEA, and STN and/or CEA were 28, 42, and 55%, respectively. There was no significant correlation between STN and CEA in these cancers. STN may be a useful serum marker for digestive cancers, especially gastric and colorectal cancers. PMID- 1891176 TI - Anthracycline cardiotoxicity: in vivo and in vitro effects on biochemical parameters and heart ultrastructure of the rat. AB - The premise of this study is that mitochondrial lesions caused by anthracyclines lead directly to cardiotoxicity. We compared several biochemical parameters, including endogenous cellular respiration, adenosine and guanosine triphosphate levels, and 14C-amino acid incorporation, of rat hearts treated with doxorubicin and some of its derivatives, recent products of pharmacological research aimed at selecting less toxic antiblastic agents. In rats treated in vivo, we further examined the ultrastructural changes induced by anthracycline antibiotics in order to elucidate which biochemical parameters were consistent with the morphological lesions. Our data indicate that mitochondria are the target of the anthracycline effects and that oxygen uptake and nucleotide levels may be regarded as markers of the toxicity when evaluating new drugs before their clinical use. The lack of cytoplasmatic or endoplasmatic reticulum alterations may account for the failure of anthracyclines to affect amino acid incorporation. In any event, the rate of protein synthesis cannot serve as a marker of cardiac toxicity. In this context, epidoxorubicin and iododoxorubicin are two derivatives characterized by less cardiotoxic potential than doxorubicin and thus appear to be promising antiblastic agents. PMID- 1891177 TI - Comparative pharmacokinetics of chlorambucil and prednimustine after oral administration. AB - The pharmacokinetics of chlorambucil, phenylacetic acid mustard (the beta oxidation product of chlorambucil), and prednisolone were investigated in a cross over study after oral administration of chlorambucil (30 mg) + prednisolone (50 mg) versus prednimustine (300 mg), the ester of chlorambucil and prednisolone. Intact prednimustine could not be detected in plasma at any time. After administration of prednimustine, the plasma concentration-time curves of chlorambucil, phenylacetic acid mustard, and prednisolone showed a retarded profile compared to the administration of the single components. The mean bioavailability was 14% for chlorambucil, 21% for phenylacetic acid mustard, and 22% for prednisolone, when given as prednimustine, compared to the administration of free compounds in stoichiometrically equivalent doses. When given in the oral dosages mentioned above, the average dose-intensity was 62% for chlorambucil, 95% for phenylacetic acid mustard, and 72% for prednisolone, indicating sufficient therapeutic concentrations of the detectable agents. PMID- 1891178 TI - Flowcytometric measurement of the cell cycle of experimental tumors: some devices for accurate measurement of proliferative activity. AB - In this paper we present the cell cycle analysis using the latest flowcytometer, FACScan and dedicated softwares. Although the 5-bromodeoxyuridine (BrdU) and anti BrdU method developed by Gratzner has become popular for analysis of cell kinetics, contaminating interstitial cells and cell doublets are still factors responsible for some mistakes in measuring the cell cycle accurately. These hampering cells were almost gated out on the catogram consisting of the forward scatter and DNA content (propidium iodide, PI). After that, the bivariate distribution of BrdU and PI according to the tumor growth showed reliable patterns. In LLC tumor the population, of which DNA content was compatible with S phase cells, was detected in the cytogram. Thus, the two-dimensional analysis of the cell cycle can demonstrate each population clearly. The results obtained from the BrdU method are more beneficial than autoradiography or microspectrophotometry, and reproducible data of the cell cycle parameters can be acquired with some devices described here. PMID- 1891179 TI - Carcinogenic effect of force-feeding an extract of black pepper (Piper nigrum) in Egyptian toads (Bufo regularis). AB - 50 male and 50 female Bufo regularis were treated, by force-feeding, with an extract of black pepper, at a dose level of 2 mg, 3 times a week for 5 months. The first tumors appeared after 2 months. Liver tumors (hepatocellular carcinomas, lymphosarcomas and fibrosarcomas) were found in 12 males and 18 females. Metastatic deposits of hepatocellular carcinomas were registered in the spleen, kidney, fat body and ovary. PMID- 1891180 TI - Finally, a chance for a sensible health care/disease treatment program. PMID- 1891181 TI - Corneal topography as a predictor of refractive change in the prospective evaluation of radial keratotomy (PERK) study. AB - The first operated eyes of 435 patients undergoing radial keratotomy in the Prospective Evaluation of Radial Keratotomy (PERK) study were evaluated by photokeratography to document the preoperative and postoperative corneal shape. We determined by regression analysis and analysis of variance that the corneal shape preoperatively improved the prediction of the corneal shape 6 months postoperatively in the 3-mm-clear-zone population. The reduction of myopia in all 435 eyes ranged from 1.25 to 9.75 diopters. We studied the effect of the preoperative corneal shape on this variability in the outcome of the surgery using rings 2 and 7 on photokeratography and corneal diameter. In the 3-mm-clear zone group, eyes with flat prolate corneas had a greater reduction in myopia (4.65 D); those with steeper, more spherical corneas had less reduction in myopia (3.48 D). In addition, eyes with a 3-mm clear zone and flat central corneas alone (8.0 mm = 42.19 D) flattened approximately 0.75 D more than those with steep central corneas (7.0 mm = 48.21 D). In the 3.5-mm and 4.0-mm clear zone groups, the change in corneal curvature was not related to the preoperative curvature. A stepwise regression analysis of the 151 eyes in the 3.0-mm-clear-zone population demonstrated the following predictive equation for radial keratotomy; change in cycloplegic refraction = -14.55 + [-2.097 x average ring-2 radius] + [3.605 x average ring-7 radius] + [0.69 x horizontal corneal diameter] + [0.079 x age] + [ 0.379 x spherical equivalent cycloplegic refraction]. There was a 1.17-D observed difference in the effect of radial keratotomy between those eyes with a steep/steep corneal topography (7.2% of the 3.0-mm-clear-zone population) and the flat/flat topography (29% of the 3.0-mm-clear-zone PERK population). A knowledge of corneal topography provides an additional tool for understanding the operative variability of radial keratotomy. PMID- 1891182 TI - Extracapsular cataract extraction and posterior chamber lens implantation in controlled open-angle glaucoma. AB - A consecutive series of 103 eyes, 37 with controlled simple glaucoma (SG) and 66 with capsular glaucoma (CG), underwent extracapsular cataract extraction (ECCE) and posterior chamber lens (PC-IOL) implantation. Two to 6 weeks after surgery, 48% of the SG eyes and 62% of the CG eyes had visual acuities better than 0.4, as compared with 8% and 3%, respectively, preoperatively. The corresponding figures after 12 to 43 months in the SG eyes were 62%, and after 14 to 38 months in the CG eyes, 55%. A slight increase of mean intraocular pressure (IOP), from 19.0 +/- 4.8 mm Hg to 25.3 +/- 13.3 mm Hg in the SG eyes, and from 19.0 +/- 3.9 mm Hg to 24.5 +/- 9.6 mm Hg in the CG eyes occurred 1 to 2 weeks after surgery; at 2 to 6 weeks the mean IOPs had returned to preoperative levels: 18.1 +/- 6.4 mm Hg in the SG eyes and 18.4 +/- 5.9 mm Hg in the CG eyes. After a mean of 26.5 months (range, 12 to 43 months), IOP had decreased to 17.3 +/- 2.9 mm Hg in the SG eyes; and after 24.2 months (range, 14 to 38 months) to 17.6 +/- 5.7 mm Hg in the CG eyes. The need for glaucoma medication was diminished at 2 to 6 weeks after surgery: IOP was controlled (less than 21 mm Hg) without glaucoma medication in 43% of the SG, and in 50% of the CG eyes (preoperatively, all of the SG and 89% of the CG eyes required medication).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1891183 TI - Types of posterior capsular breaks and their surgical implications. AB - We studied the pathogenesis, clinical features, and management of posterior capsular breaks in 28 cataract patients during planned extracapsular cataract extraction and intraocular lens implantation surgery. In the age-related cataract group (17 cases), the posterior capsular breaks were fresh, caused by the irrigation-aspiration cannula. Located in the upper part of the posterior capsule, they had thin margins and tended to enlarge with continued irrigation. Nine (52.9%) of these breaks could be plugged with viscoelastic, and after dry aspiration, a posterior chamber lens was implanted successfully. Posterior capsular breaks in traumatic cataracts (11 cases) were preexisting but were detected only during surgery. Centrally located, they had thick fibrosed margins and remained the same size during irrigation- aspiration. The minimal vitreous herniation seen in four (35.3%) of these cases was managed by automated partial anterior vitrectomy through the break. A posterior chamber intraocular lens was implanted in all these cases. PMID- 1891184 TI - The effect of retrobulbar anesthesia on visual acuity in planned extracapsular cataract extraction. AB - To our knowledge, this is the first evaluation of the effect of retrobulbar anesthesia on visual acuity. We compared the preoperative best corrected near visual acuity of 30 consecutive patients undergoing planned extracapsular cataract extraction with their best corrected near visual acuity 10 minutes following successful retrobulbar anesthesia. The mean decrease in acuity was 2.83 lines on a Jaeger near card. Postinjection visual acuity did not change in four eyes. In general, the longer the globe axial length, the greater the decrease in visual acuity following retrobulbar block. There was no significant correlation between postinjection acuity and patient age or volume of anesthetic injected. PMID- 1891185 TI - Dacryocystorhinostomy in osteopetrosis. AB - Osteopetrosis is a rare congenital disorder of bone metabolism characterized by generalized sclerotic bone resulting from osteoclast dysfunction. There are several ocular manifestations, one of which is nasolacrimal duct obstruction from osteosclerosis of the nasolacrimal foramen. The surgeon must anticipate and prepare for the difficulties of working with marbleized, ultra-dense bone, alternating technique accordingly. In nasolacrimal duct obstruction, surgical management produces seemingly stable long-term results. However, if ossification recurs at the operative site, reoperation may become necessary for either optic nerve decompression or dacryocystorhinostomy. PMID- 1891186 TI - Multilevel full-thickness eyelid resection for the correction of severe acquired ptosis in the poorly functioning eyelid. AB - Six eyelids (4 patients) with severe myogenic (4 eyelids), neurogenic (1 eyelid), or mechanical (1 eyelid) ptosis underwent surgical correction with a multilevel full-thickness resection of eyelid tissue combined with a plication of the levator aponeurosis-Muller's muscle complex. All eyelids had poor levator function, fair to poor orbicularis function, and a poor Bell's phenomenon. In all cases, the upper eyelids were elevated to an acceptable functional level without exposure keratopathy. This resection procedure preserves orbicularis function while allowing correction of severely ptotic eyelids with poor levator function, providing an acceptable alternative to other techniques for correcting this problem. PMID- 1891187 TI - Simplified limbal incision for extraocular rectus muscle surgery. AB - We describe a limbal incision for extraocular muscle surgery which involves only one incision to the conjunctival-Tenon's layer instead of the three separate incisions required in the standard limbal approach. Based on the 316 extraocular muscle operations in which we have used this one-snip procedure, we conclude that it is simpler and faster than the standard limbal incision, and that it provides good surgical exposure and probably less tissue damage. PMID- 1891188 TI - Isolated fractures of the orbital floor: risk of infection and the role of antibiotic prophylaxis. AB - The application of antibiotic prophylaxis to fractures of the orbital floor is controversial. The incidence of infection following this injury remains undefined. We report a case of orbital cellulitis following orbital floor fracture, and attempt to define guidelines for the appropriate use of antibiotics in the setting of an isolated blowout fracture. PMID- 1891189 TI - Infectious crystalline keratopathy occurring in an eye subsequent to glaucoma filtering surgery with postoperative subconjunctival 5-fluorouracil. AB - We present a case of infectious crystalline keratopathy occurring after 5 fluorouracil filtering surgery. The patient had discrete, branching, white crystalline lesions in the anterior corneal stroma. Cultures grew Streptococcus viridans, and gram-positive cocci were demonstrated in corneal tissue biopsy specimens. Toxic and immunosuppressive properties of 5-fluorouracil may have participated in the pathogenesis of the infectious crystalline keratitis. PMID- 1891190 TI - Total pupillary capture with a foldable silicone intraocular lens. AB - We report a case of total pupillary capture on the 1st postoperative day in a patient who had undergone phacoemulsification and placement of a silicone foldable posterior chamber intraocular lens. Anterior displacement of the lens optic resulted in 2.25 diopters of induced myopia. Dilation of the pupil corrected the lens capture and reversed the induced myopia, yielding a refraction of plano. Higher rates of pupillary capture have been associated with sulcus fixation and nonangulated flexible (polypropylene) haptics. Contraction of the capsular bag on the flexible polypropylene haptics of this silicone lens is thought to force the optic anteriorly, increasing the probability of lens capture by the iris. PMID- 1891191 TI - Effects of rigid contact lens edge lift changes on tear pump efficiency. AB - The effects of rigid contact lens axial edge lift changes on corneal oxygenation and tear exchange with the blink were studied for lenses of five axial edge lifts (0.05 to 0.13 mm in 0.02-mm steps). The overall and optic zone diameters were maintained at 8.8 and 7.4 mm, respectively, and all other parameters were held constant. Oxygen uptake rates were measured for the normal open eye after 5 min of static (without blinking) and dynamic (with blinking once every 5 s) contact lens wear. As expected, no significant differences were found in the oxygen uptake rates associated with the static wear of the contact lenses; however, under dynamic conditions, increasing edge lift was associated with a reduction in oxygen demand. The differences between data obtained under static and dynamic conditions increased with increasing axial edge lift, and subjects with small palpebral aperture sizes seemed to benefit more from increasing axial edge lift. PMID- 1891192 TI - Fate of water in the soft contact lens immediately after lens placement onto the cornea. AB - Soft contact lenses presoaked in D2O or H2(17)O were used to examine the movement of water immediately after their placement onto the eye. Two experiments were conducted: (1) the rate of D2O loss from these soft lenses was determined by assaying residual D2O with nuclear magnetic resonance spectroscopy; and (2) the movement of water into/inside the eye was followed by tracking the path of H2(17)O using magnetic resonance imaging. D2O dissipation occurred in two phases: an initial rapid washout (1.25 ml/h) followed by a slower phase (0.13 ml/h). The latter was eliminated by previous contact lens wear. The H2(17)O study showed that once water entered the anterior chamber, it rapidly exchanged with water in the ocular (predominantly iris) circulation (flow rate constant = 0.1/min). It appears that exogenous water, in this case water from the soft lens, ultimately interacts with the ocular circulation. This is one aspect of cornea-soft lens interaction previously unreported. PMID- 1891193 TI - Effects of spherical and astigmatic defocus on acuity and contrast sensitivity: a comparison of three clinical charts. AB - Two contrast sensitivity charts (Vistech and Pelli-Robson) have become available to the eye care practitioner. Their value as clinical tools for the assessment of visual function may be enhanced because of either an insensitivity to the effects of optical focus or a hypersensitivity to defocus. We compared the sensitivity to defocus of these charts to the traditional Snellen chart by examining the effect of up to +/- 5.00 D of spherical and astigmatic defocus on performance with each chart. In order to simulate the two types of clinical examination scenarios, tests were performed both with and without mydriatic/cycloplegic agents. The Pelli-Robson contrast sensitivity chart was very resistant to the effects of all types of optical defocus. As predicted, the high spatial frequencies on the Vistech chart were sensitive to defocus. However, although contrast sensitivities for the low frequencies were affected less, optical defocus produced significant decreases in low frequency Vistech contrast sensitivity. In addition, the Vistech chart was very insensitive to axis 180 blurring lenses. There was no indication that either contrast sensitivity chart was more sensitive to defocus than the standard Snellen chart. PMID- 1891194 TI - Magnetostimulation of vision: direct noninvasive stimulation of the retina and the visual brain. AB - The history of magnetophosphenes and their closely related predecessor, electrophosphenes, is described from the mid-18th century to the present time. The current era of magnetic stimulation started in 1985 with the development of a practical capacitor-discharge electromagnetic stimulator by Barker and his colleagues at the University of Sheffield, and their application of it to the brain with Merton and Morton at the National Hospital, London. The safety of magnetostimulation of the brain is discussed as well as the advantages of magnetostimulation over electrostimulation. Principles of magnetostimulation of nerves and magnetic measurement are considered. Effects on motor and sensory systems of the brain are described including magnetic perceptual suppression in the visual cortex and other pioneering work of Amassian, Cracco and Maccabee at SUNY Health, Brooklyn. Magnetophosphenes from retinal and cortical magnetostimulation are distinguished. Now that visual cortical stimulation is possible with the strong magnetic pulses generated by capacitor-discharge instruments, the functional viability of the visual cortex may be tested directly and noninvasively. PMID- 1891195 TI - Vergence orthoptics: validity and persistence of the training effect. AB - The validity and permanence of orthoptic treatment for vergence deficiencies requires investigation due to the subjective nature of determining success in most clinical cases, i.e., the amelioration of symptoms and increases in vergence ranges. The relation between Risley prism vergences, a subjective measure, and vergence tracking rate, an objective index, is investigated. The course of orthoptics progress is compared in cases of clinical vergence dysfunction. Vergence-deficient control subjects showed no significant change in either index. However, trained subjects demonstrated rapid increases in both indices. The persistence of the training effect was monitored for up to 9 months. No regression was observed in subjects who met all release criteria, but one subject who chose to terminate therapy early showed a slow regression in tracking rate and recurrence of symptoms. These data support the validity of vergence training and increase the plausibility of previous clinical reports of orthoptics success. PMID- 1891196 TI - Assessment of cycloplegic effects on the vistech contrast sensitivity test in Army aviator candidates. AB - This study was designed to provide information regarding two aspects of contrast sensitivity testing of aviator candidates: first to determine whether contrast sensitivity functions (CSF's) obtained with the Vistech Visual Contrast Test System (VCTS) are affected by cycloplegia and second to determine whether the VCTS provides useful CSF's under clinical screening conditions in a timely and simple manner. Contrast sensitivity thresholds were obtained at 5 spatial frequencies from 106 aviator candidates before and after administering a cycloplegic. CSF's obtained under cycloplegia were reduced by about 20%. The VCTS provided useful CSF's under military screening conditions, and added about 6 min to the time required for the standard flight physical. PMID- 1891197 TI - Relation between the chromatic difference of refraction and the chromatic difference of magnification for the reduced eye. AB - We provide a simple model for calculating the chromatic difference of magnification for the human eye. Spectral differences in image size are proportional to the eye's longitudinal chromatic aberration and the axial distance between the entrance pupil and nodal point. We verify that the model provides magnification estimates equal to previously published predictions, and we show the significant increase in this aberration produced by experimental use of artificial pupils. PMID- 1891198 TI - Proof that the prismatic effect is perpendicular to the lens thickness contour. AB - It is sometimes assumed that the prismatic effect in any astigmatic lens is orthogonal or perpendicular to the iso-thickness curves. This paper offers a formal proof of the validity of the assumption. PMID- 1891200 TI - Statistics notebook: Entry II.C: Masked studies. PMID- 1891199 TI - Noncontact tonometry in children. AB - A hand-held noncontact tonometer (Pulsair, Keeler Ltd., UK) was tested in 42 children, from 5 months to 12 years of age. At least 1 intraocular pressure (IOP) reading was obtained in all of the 84 eyes studied, whereas with a Goldman applanation tonometer measurements could be obtained in only 26 eyes (14 subjects). Time required for examination with the Pulsair was quite variable and related to age (p less than 0.0001). Compliance in children was reported as "good" in the majority of cases; it was also age-related (p less than 0.005). Although its reliability could not be definitely evaluated, the results of this study indicate that this instrument may be a valuable choice for screening and follow-up purposes in childhood. PMID- 1891201 TI - Multiple images produced by retinal image defocus. PMID- 1891202 TI - Hazards of visual training. PMID- 1891203 TI - Corneal distortion and monocular diplopia. PMID- 1891204 TI - Postkeratoplasty astigmatism. PMID- 1891205 TI - The ophthalmologist's role in diagnosing child abuse. PMID- 1891206 TI - Perforating ocular injuries caused by anesthesia personnel. AB - Between February 1988 and May 1990, the authors treated 12 perforating ocular injuries caused by anesthetic injections around the eye. All 12 injections were performed by nonophthalmologists. Eleven were performed by anesthesiologists and one by a certified nurse anesthetist. Five were caused by blunt needles and seven by sharp needles. Two of the eyes had multiple posterior exit wounds. The five eyes that had sharp needle, single perforations (i.e., one entrance wound and one exit wound) were easily managed with cryopexy, laser, or observation. All five of these eyes have a visual acuity of 20/40 or better. Six vitrectomies were performed on the five patients with single perforations caused by blunt needles; three of these eyes have a visual acuity of counting fingers or worse. The two patients who had multiple posterior exit wounds required a total of four procedures. The visual acuity in these eyes is 20/400 and light perception. Anesthesia personnel should be well trained before attempting ocular anesthesia. The use of blunt needles does not prevent ocular penetration. PMID- 1891207 TI - Needle penetration of the globe during retrobulbar and peribulbar injections. AB - The charts of 23 patients with needle penetration of the globe during retrobulbar or peribulbar injections between January 1980 and May 1990 were reviewed. Possible needle penetration risk factors included high myopia, previous scleral buckling procedures, injection by nonophthalmologists, and poor patient cooperation during the injection. Of the 23 cases of ocular penetration, 16 (70%) were from sharp (22-, 23-, and 25-gauge) needles, and 7 (30%) were from blunt (23 and 25-gauge) needles. Management options depended on the severity of the intraocular injury. Retinal breaks without retinal detachment were treated by laser photocoagulation (four cases) or cryopexy (one case) and were observed in three cases. More advanced complications (retinal detachment and vitreous hemorrhage) were usually treated by pars plana vitrectomy with or without a scleral buckle (12 of 14 cases). The final visual acuity was 20/400 or better in only 2 of the 14 retinal detachment cases. In cases without retinal detachment, the final visual acuity was 20/50 or better in 7 of 9 cases. PMID- 1891208 TI - Optimal astigmatism to enhance depth of focus after cataract surgery. AB - A small amount of myopic astigmatism can enhance the depth of focus of the pseudophakic eye, optimally providing at least 20/30 visual acuity for both near and distance fixation. For given spherocylindrical refractive errors and fixation distances, the cross-sectional area of Sturm's conoid at the retina was calculated for a schematic eye. These data were used to determine the optimal astigmatic error needed to obtain maximum depth of focus and least theoretical blur for any given spherical equivalent refractive error. Optimal depth of focus was obtained when the plus cylindrical component equaled negative sphere - 0.25 diopters. The near and distance visual acuities of ten pseudophakic patients with induced refractive errors were highly correlated with this model. Low myopic astigmatism after cataract surgery may represent an alternative to multifocal intraocular lenses by providing spectacle independence. PMID- 1891209 TI - Pupillary size and responsiveness. Implications for selection of a bifocal intraocular lens. AB - The authors measured the pupil sizes of 132 subjects and correlated these to selected designs of annular bifocal intraocular lenses (IOLs). Pupils were measured under five different testing conditions that simulated representative visual tasks: (1) driving at night, (2) reading in dim illumination, (3) reading in bright illumination, (4) distant viewing in indirect sunlight, and (5) distant viewing in direct sunlight. Pupil size diminished with age and with increased illumination. Because of accommodative pupillary constriction, there was little difference in pupil size measured while reading in bright indoor illumination and distant viewing in indirect sunlight. Evaluating a patient's pupil size permits the individualized estimation of the eye's bifocal function following implantation of each of the annular-design bifocal IOLs. PMID- 1891210 TI - Initial 5-fluorouracil trabeculectomy in uncomplicated glaucoma. AB - The effectiveness of trabeculectomy with adjunctive low-dose 5-fluorouracil (5 FU) as the initial surgical procedure in uncomplicated glaucoma was evaluated retrospectively in a consecutive series of 52 patients (mean follow-up, 18.6 +/- 11.7 mos) and 74 control subjects. The cumulative 2-year success (intraocular pressure [IOP] less than 21 mmHg) was 100% in the 5-FU group and 78.9% in the control group (P = 0.01, Wilcoxon test). The 5-FU group had a mean postoperative IOP of 12.5 +/- 4.6 mmHg versus 17.4 +/- 5.7 mmHg in the control group at 2-year follow-up (P = 0.015, t test). Antiglaucoma medications were required in 5.8% of patients in the 5-FU group and in 41.9% of controls within 2 years (P less than 0.0001, Fisher's exact test). These results suggest that low-dose 5-FU at the time of initial trabeculectomy leads to a higher success rate, lower IOP, and less need for antiglaucoma medications postoperatively. PMID- 1891211 TI - Molteno implantation for glaucoma in young patients. AB - Seventy patients younger than 21 years of age underwent Molteno implantation for nonneovascular glaucoma. Fifty-three (76%) patients had failed angle and/or conventional filtering surgery. Final intraocular pressure less than 22 mmHg (but over 5 mmHg) was achieved in 40 (62%) of the 65 patients with at least 6-month follow-up (range, 6 to 59 months; mean +/- standard deviation, 22.7 +/- 14.1 months); however, only 22 (34%) were controlled after the initial Molteno implantation procedure, and 54 (83%) patients underwent further glaucoma and/or nonglaucoma surgical procedures. The visual acuities remained within one line of their preoperative levels or improved in 25 (68%) of the 37 patients on whom Snellen acuities were available. The most frequent complications included: tube cornea touch (20%, transient in 3%), corneal edema (17%), retinal detachment (16%), tube block (10%), cataract (9%), chronic hypotony or phthisis (9%), pupillary or cyclitic membrane (9%), hyphema (7%), flat anterior chamber (6%), and large postoperative choroidal effusion (6%). Despite the high rates of subsequent surgical interventions and complications, Molteno implantation has been a useful approach for achieving intraocular pressure reduction in young patients with glucoma. PMID- 1891212 TI - Use of trabeculectomy with postoperative 5-fluorouracil in patients requiring extremely low intraocular pressure levels to limit further glaucoma progression. AB - The authors conducted a randomized, controlled clinical trial to quantify the effect of 5-fluorouracil (5-FU) on filtration surgery. Both eyes of 17 patients with either bilateral low-tension glaucoma or advanced chronic open-angle glaucoma that would be expected to progress at intraocular pressures in the normal range were included. One eye received a full-thickness filtering procedure with a modified shell tamponade technique, and the other received a trabeculectomy with postoperative 5-FU. Follow-up was equal for both eyes and averaged 9.2 months. In eyes in the shell group, the average postoperative pressure was 10.94 mmHg, and in the 5-FU group it was 6.94 mmHg, (P = 0.0001). However, the postoperative visual acuity decrease was significantly greater in the 5-FU group (P less than 0.05). Choroidal detachments also were more frequent in the 5-FU group, but this was not statistically significant. PMID- 1891213 TI - Late bleb-related endophthalmitis after trabeculectomy with adjunctive 5 fluorouracil. AB - The incidence of late-onset bleb-related endophthalmitis was evaluated retrospectively in 229 consecutive trabeculectomies performed with adjunctive 5 fluorouracil (5-FU) therapy. Mean follow-up was 23.7 +/- 16.3 months (range, 3 to 60 months). Thirteen eyes (5.7%) of 11 patients developed bleb-related endophthalmitis an average of 25.9 +/- 17.4 months (range, 5 to 58 months) after surgery. Infection occurred in 9 of 96 (9.4%) procedures performed from below and in 4 of 133 (3.0%) procedures performed superiorly (P = 0.05, Fisher's exact test). The relative risk of bleb-related endophthalmitis in trabeculectomy from below versus above is 4.0 after adjustment for age and sex (95% confidence interval = 1.1, 14.8). Trabeculectomy with adjunctive 5-FU performed from below carries an increased risk of late bleb-related infection. The incidence of late bleb-related endophthalmitis after 5-FU trabeculectomy appears to be higher than that for trabeculectomy without adjunctive 5-FU injections. PMID- 1891214 TI - Long-term efficacy of repeat argon laser trabeculoplasty. AB - The role of repeat argon laser trabeculoplasty (RALT) in the management of open angle glaucoma is controversial. To determine the long-term efficacy of RALT, the authors reviewed case records of 44 patients (50 eyes) who received RALT for uncontrolled glaucoma at the Wills Eye Hospital before 1986. Success was defined as a 3 mmHg or greater decrease in intraocular pressure (IOP) to less than 22 mmHg, and no further surgical intervention. By life table analysis, RALT was successful in 35% of eyes at 6 months, in 21% at 12 months, in 11% at 24 months, and in 5% at 48 months. Thirty-three percent of eyes in which primary ALT was successful for 1 year were successful 12 months after RALT. Complications included IOP spikes in 12%. In conclusion, RALT was generally not effective for long-term control of open-angle glaucoma, but may be useful as a temporizing measure. However, this use of RALT must be weighed against the risks of complications and the additional progression of disease before more definitive surgical intervention. PMID- 1891215 TI - Effect of cataract on automated perimetry. AB - Humphrey visual fields (30-2 program) were performed on 24 otherwise healthy patients before and after cataract extraction to examine the effect of cataract on automated visual fields. All patients met reliability index criteria and recovered visual acuity of 20/25 or better. The effect of learning associated with repeated testing was controlled with visual fields of the fellow eye. Although a greater absolute threshold recovery occurred in the central region of the visual field after cataract extraction, the percent of threshold recovery did not vary across the visual field except for the most peripheral testing points, which demonstrated less recovery. Thus, cataracts depress an automated visual field fairly uniformly. Clinical grading of cataracts by a single experienced clinician was generally a poor predictor of visual field loss. Only the presence of posterior subcapsular plaque in the visual axis and the preoperative visual acuity correlated significantly with postoperative central threshold recovery. Pattern standard deviation remained unchanged after cataract removal, confirming it as a useful way of estimating visual loss from cataracts. PMID- 1891216 TI - The nonapproved use of medications. AB - The need for new treatments for both established and recently described disorders has heightened awareness of the drug approval process. In particular, many ophthalmologists have questioned the ramifications of using approved drugs in nonapproved settings (such as apraclonidine) and the means of obtaining investigational drugs for patient use. The authors review the legal structures established to address these concerns and recommended approaches ophthalmologists can take to minimize their exposure to legal complications. PMID- 1891217 TI - Additivity of prostaglandin F2 alpha-1-isopropyl ester to timolol in glaucoma patients. AB - The effect on intraocular pressure (IOP) of adding prostaglandin F2 alpha-1 isopropyl ester (PGF2 alpha-IE) to timolol was studied in 21 eyes of 13 patients with newly diagnosed primary open-angle glaucoma that was inadequately controlled with timolol alone. After at least 2 weeks of twice daily timolol 0.5% therapy, PGF2 alpha-IE, 0.5 microgram in 30 microliters, was topically applied twice daily at 8 AM and 8 PM, 5 minutes before each timolol dose, for 7 days. Intraocular pressures were measured before timolol treatment, and at 8 AM, 8:30 AM, 12 PM, 2 PM, and 4 PM on the day before the addition of PGF2 alpha-IE, and on day 1 and on day 7 of combined therapy. Mean IOP was 39 +/- 2 mmHg (+/- standard error) before timolol therapy and 31 +/- 2 mmHg after at least 2 weeks of treatment with timolol alone. A significant (P = 0.004) further reduction of IOP was first observed 4 hours after the first dose of PGF2 alpha-IE, which was maintained throughout the duration of combined therapy. During the last day of combined treatment and at 12 hours after the final dose, IOP was reduced a mean of 6 to 9 mmHg (mean, 9.0 +/- 1.5 mmHg at 12 hours) below baseline values obtained with timolol alone. These results indicate that adding PGF2 alpha-IE in patients treated with timolol causes a further reduction of IOP that may prove to be clinically useful in glaucoma therapy. PMID- 1891219 TI - Evaluation of eyes with advanced stages of retinopathy of prematurity using standardized echography. AB - The authors evaluated 36 patients (72 eyes) who had either Stage 4 or Stage 5 retinopathy of prematurity (ROP) with standardized A-scan and B-scan echography. The eyes were evaluated for vitreous opacities, retrolental membranes, and retinal detachments. Stage 5 retinal detachments were present in 94% (68 of 72) of the eyes with 65% (47 of 72) having a wide anterior and narrow posterior configuration. Anterior retinal loops were noted in 36% of the eyes. Subretinal opacities were present in 47% of the eyes. Choroidal thickening and intraocular calcium were noted in 22% and 14% of eyes, respectively. The axial eye length was measured and adjusted for the differences in chronological and gestational age and compared with data from normal eyes. This showed that eyes with ROP were much smaller. The standardized A-scan was helpful in confirming the diagnosis of retinal detachment, evaluating the peripheral retina, and examining the subretinal space. The combination of A-scan and B-scan echography is helpful in predicting anatomic findings in patients with ROP undergoing surgery. PMID- 1891218 TI - Management of late-onset angle-closure glaucoma associated with retinopathy of prematurity. AB - Late-onset angle-closure glaucoma secondary to retinopathy of prematurity (ROP) occurred in ten eyes of ten patients. The age at presentation ranged from 12 to 45 years (mean, 32 years). Eight eyes had nonneovascular mechanisms for the angle closure while two had neovascular angle closure. Treatment of eyes with this form of secondary angle closure included medical management alone, peripheral iridectomy, trabeculectomy, lensectomy, alloplastic tube shunt implantation, and cilioablative procedures. Three eyes required more than one of these treatments. The choice of therapy was based on the initial intraocular pressure and vision, degree of lens opacity and intumescence, presence of anterior segment neovascularization, and the gonioscopic appearance of the anterior chamber angle. The clinical features of this condition are described and a proposed mechanism and therapeutic approach are presented. PMID- 1891220 TI - Management of advanced retinopathy of prematurity in the older patient. AB - The authors studied 11 eyes of 10 patients who complained of a recent decrease in vision and whose eyes had the clinical appearance of stage 5 retinopathy of prematurity (ROP) as diagnosed by the presence of a dense, opaque retrolenticular membrane. Patients ranged in age from 4 to 33 years, and birth weights ranged from 680 to 1077 g. All eyes underwent vitrectomy, lensectomy, and membrane peeling and were found intraoperatively to have areas of retina that were attached (stage 4B). Preoperatively, a reproducible visual-evoked potential waveform appeared to better predict this retinal configuration and potential retinal function than did the contact B scan ultrasound of the globe. Postoperatively, seven (63.6%) eyes demonstrated an improvement in vision. Vitreous surgery may be beneficial in selected eyes of older patients with advanced ROP to clear media opacities and to uncover areas of functional, attached retina, which may allow these patients to more effectively use the vision they possess. PMID- 1891221 TI - Vitrectomy for premacular fibroplasia. Prognostic factors, long-term follow-up, and time course of visual improvement. AB - Two hundred seventy eyes with premacular fibroplasia consecutively treated by pars plana vitrectomy and membrane peeling were reviewed. This study is among the largest series with long-term follow-up reported to date. Visual improvement of two or more lines was achieved in 43% of eyes at 6 to 12 months, in 54% at 1 to 2 years, in 60% at 2 to 3 years, and in 58% at 3 to 5 years. Overall, complications occurred in 34 eyes (13%). Cataract progression after vitrectomy was noted in 106 (57%) of phakic eyes at 3 to 5 years, and 43 of these eyes underwent subsequent cataract extraction. Mean time to best visual acuity after vitrectomy was slightly less than 1 year for all eyes unless they had cataract worsening with subsequent cataract extraction (1.9 years). Significant factors affecting visual outcome were: preoperative lens status, visual acuity before vitrectomy, duration of preoperative symptoms of distortion and/or blurred vision, and the occurrence of intraoperative complications. PMID- 1891222 TI - Pneumatic retinopexy. A two-year follow-up study of the multicenter clinical trial comparing pneumatic retinopexy with scleral buckling. AB - The authors report 2-year follow-up information on 179 of 198 eyes (90%) enrolled in a previously published multicenter, randomized, controlled clinical trial comparing pneumatic retinopexy (PR) with scleral buckling (SB) for the management of selected retinal detachments. Scleral buckling was compared with PR with regard to redetachment after the initial 6-month follow-up period (1% versus 1%), overall attachment (98% versus 99%), subsequent cataract surgery (18% versus 4%; P less than 0.05), preoperative visual acuity (no significant difference), and final visual acuity of 20/50 or better in eyes with macular detachment for a period of 14 days or less (67% versus 89%; P less than or equal to 0.05). Reoperations after a failed PR attempt did not adversely affect visual outcome. After 2 years, PR continues to compare favorably with SB. PMID- 1891223 TI - Vitreoretinal traction and perimacular retinal folds in the eyes of deliberately traumatized children. AB - The pathophysiology of perimacular folds in eyes of deliberately traumatized children is disputed. The authors reviewed the clinical and forensic records and systemic and ocular findings at autopsy of three children with perimacular retinal folds who died after being violently shaken. Two of the children suffered direct head trauma in addition to being shaken; one patient was violently shaken without any physical or forensic evidence of direct head trauma. No direct ocular trauma was detected. In each case, the vitreous had partially separated from the retina but remained attached to the internal limiting membrane at the apices of the folds and the vitreous base, implicating traction in the pathogenesis of these folds. Although some intraocular findings in deliberately traumatized children may be explained by direct head injury, the possibility of both direct head trauma and shaking must be considered. Perimacular folds may develop without direct ocular or head trauma and may constitute evidence supporting violent shaking. PMID- 1891224 TI - Kinetic ultrasound evaluation of the posterior vitreoretinal interface. AB - The evaluation of the posterior vitreoretinal interface is important in the study of the natural course and preoperative evaluation of numerous disorders of the retina. The exact status of the posterior vitreous cannot always be reliably determined by ophthalmoscopic examination. The diagnostic value of kinetic contact ultrasonography was investigated to evaluate the status of the posterior vitreous in 70 eyes with clear ocular media. Contact B-scan ultrasound provided an extremely accurate method for evaluating the posterior vitreoretinal interface in 69 of the 70 eyes in this study, when compared with all conventional clinical means of examination including slit-lamp biomicroscopy with the Goldmann contact lens and fundus photography with the El Bayadi-Kajiura lens. Contact B-scan ultrasonography is an important diagnostic adjunct in determining the status of the vitreoretinal interface. PMID- 1891225 TI - Frequency of adverse systemic reactions after fluorescein angiography. Results of a prospective study. AB - Intravenous fluorescein angiography is a commonly performed and extraordinarily valuable diagnostic procedure. The frequency of adverse reactions after angiography has varied considerably in previous reports. In a prospective study of 2789 angiographic procedures in 2025 patients, the authors found that the percentage of adverse reactions depended strongly on the patient's angiographic history. Overall, adverse reactions followed 4.8% of the angiographic procedures. These reactions included nausea (2.9%), vomiting (1.2%), flushing/itching/hives (0.5%), and other reactions (dyspnea, syncope, excessive sneezing) (0.2%). No cases of anaphylaxis, myocardial infarction, pulmonary edema, or seizures occurred. The percentage of reactions was 1.8% for patients who had had previous angiography without ever having had an adverse reaction. In contrast, the percentage of reactions was 48.6% for patients who had had an adverse reaction to angiography previously. PMID- 1891226 TI - Median lip fissure: etiology and suggested treatment. AB - In a prospective study of 20 patients with median lip fissure, pedigrees were obtained. A hereditary predisposition for weakness in the first branchial arch fusion seems to exist. In some persons, more often in males than in females, this weakness eventually leads to development of a median lip fissure. The fissure becomes symptomatic when it is infected. In 10 patients the fissure was excised; in the other 10 patients excision was done in combination with a Z-plasty of the center of the lesion. The prognosis with the latter operation was superior to that with the former. PMID- 1891227 TI - The comparative antimicrobial effect of calcium hydroxide. AB - The antimicrobial effectiveness of calcium hydroxide, camphorated paramonochlorophenol, and formocresol in root canals of extracted human teeth was compared. Canals in single-rooted teeth were enlarged and inoculated with Streptococcus mutans, Actinomyces viscosus, and Bacteroides gingivalis or Bacteroides fragilis. After treatment with a test agent and sealing and incubation for 1 hour, the canal contents were analyzed for the number of viable test bacteria and compared with that of inoculated teeth not treated with test agents. All test agents exhibited antimicrobial activity against all bacteria, with percent reductions in viable bacteria ranging from 64.3% to 100%. The combined data for Pulpdent paste and calcium hydroxide showed significantly higher antimicrobial activity than the combined data for camphorated paramonochlorophenol and formocresol for S. mutans and B. gingivalis or B. fragilis but showed no difference for A. viscosus. PMID- 1891228 TI - Histologic evaluation of the pulpal response to temperature probe placement in the Macaca fascicularis monkey. AB - A method to measure intrapulpal temperatures during cavity preparation and restorative procedures has been developed. It involves placement of temperature probes to the dentinoenamel and dentinopulpal junctions. After placement of the probes, the pulps of the test teeth were examined histologically to determine whether their placement caused a pulpal response. The test teeth displayed no adverse response in the areas of the pulp opposite or adjacent to the position of the probes. Therefore the developed method of temperature probe placement to measure intrapulpal temperatures does not interfere with those measurements by adversely affecting the pulp tissues. PMID- 1891229 TI - Castable glass ceramic crowns and their reaction to endodontic therapy. AB - The purpose of this investigation was to determine how castable glass (Dicor) crowns would react to both cold testing and endodontic access intervention. Full crown preparations were made on six extracted maxillary teeth. The teeth were then forwarded to Dentsply International, York, Pa. Six castable glass crowns were fabricated to fit these teeth and returned to us. Subsequently the teeth were dried and the crowns were cemented. Scanning electron micrographs of the cemented crowns were made, and endodontic access openings were drilled. The teeth were also cold tested with standard methods. The teeth were then again subjected to scanning electron microscopy to determine any changes the crowns might have undergone. One crown cracked around the gingival collar as scanning electron microscopy was performed. The other crowns did not exhibit any problems such as cracking or crazing from either the access openings or the cold testing. PMID- 1891230 TI - Automatic processing: effects of temperature and time changes on the sensitometric properties of light-sensitive films. AB - The effects of changes in the processing temperature and time of automatic processors were studied with three light-sensitive Kodak films: (1) blue sensitive X-Omat RP film, (2) green-sensitive T-Mat G film, and (3) ultraviolet sensitive X-Omat duplicating film. Speed and inherent contrast were derived for each of the three films from sensitometric curves at six different temperatures and at five different processing times. The T-Mat G film (T-grain technology) was comparatively less sensitive than conventional films (X-Omat RP) to increases in processing temperature or time. Unlike dental intraoral films, which cannot be processed at low processing time or temperature, the light-sensitive films were of archival storage quality even at a low processing time of 2.5 minutes or at a low processing temperature of 21 degrees C. Therefore the processing time of an automatic processor may be decreased for light-sensitive films. PMID- 1891231 TI - Dentin dysplasia: review of the literature and a proposed subclassification based on radiographic findings. AB - The literature is reviewed to determine the radiographic appearance of the reported cases of dentin dysplasia. The sometimes confusing nomenclature is rationalized. Four distinct forms of dentin dysplasia type I and one form of dentin dysplasia type II are identified. There seems to be no need to identify more than two distinct types of this relatively rare inherited defect of human dentin, but a proposed subclassification of type I dentin dysplasia could make identification of the two types easier. PMID- 1891232 TI - Desmoplastic fibroma of the maxillary sinus. Report of a case and review of the literature. AB - A desmoplastic fibroma of the maxillary sinus is reported in a 15-year-old boy. Desmoplastic fibroma is a rare benign tumor in the maxillofacial region. The features of this case and of 49 previously described lesions are analyzed and discussed. PMID- 1891233 TI - Cross-sectional tomography. PMID- 1891234 TI - Fractured tooth, fifteen years later. PMID- 1891235 TI - Diminished radiographic contrast between calculus and dentin. PMID- 1891236 TI - Oligodontia and transposition. PMID- 1891237 TI - Cervical necrotizing fasciitis of odontogenic origin. AB - Necrotizing fasciitis is a severe soft tissue infection caused by both aerobic and anaerobic bacteria and is characterized by a rapid extension along fascial planes and by necrosis of soft tissues. The disease rarely occurs in the head and neck. Three cases of necrotizing fasciitis of the neck after a dental infection are presented. The difficulty in diagnosing the early stage of this condition in relation to other soft tissue infections of odontogenic origin in the neck is discussed. The importance of an early diagnosis followed by an appropriate combination of medical, surgical, and dental treatment is emphasized. PMID- 1891238 TI - Recurrent buccal space abscesses: a complication of Crohn's disease. AB - A patient is described with generalized gastrointestinal involvement by Crohn's disease. Symptoms of recurrent ulceration and mucosal tags are well-described oral manifestations of Crohn's disease; however, in our patient recurrent facial abscesses, which required extraoral drainage, also developed. This complication has not previously been reported. PMID- 1891239 TI - Reversing intravenous sedation with flumazenil. AB - This study was designed to evaluate the effects of flumazenil in reversing sedation from midazolam and meperidine after oral surgical procedures. Of the 35 patients entered, efficacy was evaluated in 33 and safety in 34. Patients were tested for sedation, psychomotor skills, and memory during a 3-hour period and at a 24-hour follow-up. Flumazenil almost totally reversed the effects of sedation for approximately 2 hours, after which some loss of effect was observed. A number of central nervous system-related side effects were observed in the flumazenil group, but none of these was considered serious. One patient in the flumazenil group had an episode of hypotension that precluded further testing. PMID- 1891241 TI - Osteomyelitis of the mandible as a result of sickle cell disease. Report and literature review. AB - Only five cases of osteomyelitis of the mandible as a result of sickle disease have been published. We report another case, which uniquely affected not only the osseous portion of the mandible, including the condyle, but also the adjacent musculature. Radical resection of the involved hard and soft tissue was necessary to cure the patient. Two possible etiologies are discussed. The first states that the sickle cell crisis caused a tissue anoxia in which this tissue became secondarily infected; the second states that the preexisting infection triggered or augmented the sickling phenomena. PMID- 1891240 TI - Pneumoparotid: a case report. AB - Pneumoparotid is an unusual condition resulting from air being forced into the parotid ductal system. When it develops, it is a result of increased intraoral air pressure. Diagnosis is based on the etiologic factor, palpatory evidence of tissue emphysema, the escape of frothy saliva from the involved duct, and the sialographic finding of retained ductal air and ductal infection. PMID- 1891242 TI - Clinical features of Behcet's disease. Report of four cases. AB - Behcet's disease is a multisystem inflammatory disorder of unknown etiology. The unifying histologic reaction pattern is a leukocytoclastic vasculitis that affects predominantly the skin, oral mucosa, and eyes. Many other sites of involvement have been reported but are inconsistently found in individual patients. Early recognition and treatment of Behcet's disease may help prevent devastating permanent sequelae such as blindness. Because oral involvement is often the first manifestation of this disorder, dental practitioners are in a unique position to help these patients. We report four cases of Behcet's disease in North American patients. Diagnostic criteria and treatment options are reviewed. PMID- 1891244 TI - Differences in salivary flow rates in elderly subjects using xerostomatic medications. AB - Stimulated whole salivary flow rate (SWSFR) was measured in a group of elderly subjects who were examined for the use of xerostomia-inducing medications. SWSFR was significantly reduced in elderly subjects using one of these medications when compared with control subjects (0.94 vs 1.52 ml/min). Increasing use of up to four different xerostomia-inducing medications did not result in additional significant reduction of stimulated salivary flow rate. Psychotropic and diuretic agents were the most commonly used xerostomatic medications, and these were almost equally potent in reducing mean flow rate (0.79 vs 0.84 ml/min). The use of potentially xerostomatic medications did not affect decayed, missing, or filled surface scores or unstimulated whole saliva pH values. A weak, statistically significant, positive correlation (r = 0.39, p less than 0.01) was found between subject age and salivary flow rate in this population of elderly subjects, and this suggests that SWSRF is influenced more by factors such as medication than by aging. PMID- 1891243 TI - Oral leukoplakia and adolescent smokeless tobacco use. AB - The recent increase in smokeless tobacco (ST) use has prompted investigators to assess the health effects of ST use. This study attempted to evaluate the prevalence of oral leukoplakia among adolescent users and to determine factors associated with its presence. During their annual physical examination, 1116 teenaged football players (567 black, 546 white) answered a 34-question survey and received an oral screening examination. Results indicated that 0.5% of nonusers, 1.5% of previous users, and 13% of current users had clinically evident oral leukoplakia. Factors statistically associated with higher leukoplakia rates included history of ST use, regular ST use, years of ST use, and the weekly quantity consumed. Factors not associated included use of alcohol, use of cigarettes, type of ST used, and hours of ST use. One brand of snuff was found to be associated with a relative risk of leukoplakia higher than that of another brand of snuff. Overall, in ST users oral leukoplakia was six times more likely to develop than in nonusers. Earlier ages of ST use may lead to greater periods of use (in years) and to possible increases in deleterious long-term health effects in current adolescents. PMID- 1891245 TI - Peripheral (extraosseous) calcifying odontogenic cyst. A review of forty-five cases. AB - The peripheral calcifying odontogenic cyst (PCOC) is a rare lesion. The number of well-documented cases reported in the English-language literature until now is 38. The purpose of the present study is twofold: (1) to report seven new cases of PCOC and (2) to review and analyze the clinical and histomorphologic features of the previously reported cases of PCOC together with those of the present study. Most of the lesions were located in the maxillary and mandibular gingiva or alveolar mucosa anterior to the region of the first molar. Histologically, 66% of the lesions were of the cystic variant and 34% of the solid (neoplastic) variant. The terminology of the lesion and its histogenesis are discussed. PMID- 1891246 TI - Glandular odontogenic cyst: clinicopathologic analysis of three cases. AB - The glandular odontogenic cyst is a rare cyst of odontogenic origin, first described in 1988 by Gardner et al. Three previously unreported glandular odontogenic cysts are presented; none recurred after the initial surgical treatment, and one example was associated with a squamous odontogenic tumor-like proliferation in the wall. Ten similar cases were found in the literature, and their clinical and roentgenographic features, and follow-up, have been compared with the present cases. PMID- 1891247 TI - Plexiform granular cell odontogenic tumor: unicystic variant. AB - Plexiform granular cell odontogenic tumor of the mandible has recently been described. The cardinal histopathologic feature, as its name suggests, is a monophasic plexiform pattern of granular cells; the principal tumor in the differential diagnosis is granular cell ameloblastoma. Unlike the two previously reported cases of plexiform granular cell odontogenic tumor, which occurred as solid tumors in elderly men, the lesion reported here is a unicystic variant occurring in a middle-aged woman. PMID- 1891248 TI - Peripheral odontogenic fibroma: a clinicopathologic study. AB - The clinicopathologic features of 30 cases of peripheral odontogenic fibroma are reviewed. The age distribution is wide (11 to 76 years), and there is a slight predilection for males. The majority of the lesions (93%) occurred in blacks on the attached gingiva, and with equal frequency in the maxilla and mandible. Size varied between 1 and 3 cm in diameter. One case recurred after 14 months. Histologically, the lesions are nonencapsulated and poorly delineated. The amount of odontogenic epithelium varies considerably and consists usually of small islands or strands, although larger follicles are sometimes present. In one case the epithelial cells had a clear cytoplasm, whereas in another it was granular and eosinophilic. Origin from the surface oral mucosa can sometimes be seen. The connective tissue component is usually cellular, but collagenous, myxomatous, and mixed forms occur. Calcifications were present in 22 cases and consisted of tissue interpreted as either dentinoid, cementum, bone, or dystrophic calcific material. PMID- 1891249 TI - Unique odontogenic tumor with dentinogenesis and features of unicystic plexiform ameloblastoma. AB - A case of an atypical odontogenic tumor with features of unicystic plexiform ameloblastoma and odontoblastic differentiation with deposition of tubular dentin matrix is reported. The significance of dentinogenesis, amelogenesis, and calcification in odontogenic tumors is discussed. PMID- 1891250 TI - Acute pulpal-alveolar cellulitis syndrome. V. Apical closure of immature teeth by infection control: the importance of an endodontic seal with therapeutic factors. Part 2. AB - During orthodontic treatment to promote eruption of maxillary and mandibular second bicuspids, a young male patient had a severe endodontic cellulitis of a mandibular bicuspid. Apexogenesis and resolution of the periapical lesion was achieved by infection control with nonspecific intracanal medication without calcium hydroxide, as stated by Das. A mild periodontal cellulitis occurred shortly thereafter and rapidly resolved. A second endodontic cellulitis, after apexogenesis without an endodontic seal, occurred shortly after completion of orthodontic treatment. This also quickly resolved, and the canal was effectively sealed. This case indicates the importance of an effective endodontic seal shortly after apexogenesis is induced by infection control. This report and others on the subject indicate that apexogenesis of nonvital permanent immature teeth by infection control is a predictable endodontic treatment procedure. PMID- 1891251 TI - Carcinoid tumor of the larynx. A critical review of the literature. AB - Typical carcinoid neoplasms of the larynx are extremely rare tumors. The total number of known and documented cases is likely no more than 13. The neoplasm mainly affects males at an average age of 58 years and appears grossly as a polypoid or sessile submucosal nodule with an average 1.8 cm in size. Their predominant location is the supraglottis with the arytenoid and the aryepiglottic fold being the most frequent sites. Histologically, they are characterized by organoid architecture, uniform cellular features and lack of pleomorphism, necrosis and mitosis. Typical laryngeal carcinoids are less aggressive than their atypical counterparts but late distant metastasis and death may occur. The management of these neoplasms is conservative surgery. PMID- 1891252 TI - Atypical carcinoid tumor of the larynx. A critical review of the literature. AB - To better characterize the clinical and pathological features of the laryngeal atypical carcinoid (LAC), 127 of the published cases were analyzed. The LAC had a predilection for males (3 m:1 f), with a peak incidence in the 6th and 7th decades of life. Seventy-eight percent of patients with a relevant clinical history were smokers. Most tumors presented in the supraglottic larynx (96%) and the mean size of the measured primary lesions was 1.6 cm. The tumors were frequently argyrophil (97% of those so stained), rarely argentaffin (2 cases), and on immunohistochemistry were often reactive when stained for keratins (96%), chromogranin A (94%), and calcitonin (80%). Surgical resection was the principal modality of treatment. Of the 127 cases, metastasis to neck nodes were found in 43%, to skin or subcutaneous sites in 22%, and to distant sites in 44%. Of the 119 patients with follow-up, 49% died with tumor. The cumulative proportion surviving was 48% at 5 years and 30% at 10 years, and there were significantly worse survival rates among patients with tumors larger than 1 cm, and for patients developing tumor involvement of skin and subcutaneous tissues. Adjuvant radiation did not affect survival rates. PMID- 1891253 TI - Paraganglioma of the larynx. A critical review of the literature. AB - The clinicopathologic features of two cases of paragangliomas of the larynx are presented along with immunohistochemical, ultrastructural and DNA image analysis. The world literature is also critically reviewed in order to develop a more accurate clinicopathologic profile of the tumor. The results indicate that paragangliomas of the larynx occur in patients averaging 47 years of age and are 3 times more common in women. Most (82%) arise from the supraglottic larynx and manifest clinically as hoarseness. They are typically benign and rarely functional. Almost all alleged malignant paragangliomas of the larynx are in reality atypical carcinoids that have been misdiagnosed. Features that distinguish paragangliomas from other similar tumors are discussed. PMID- 1891254 TI - Diagnosis of urachal anomalies in infancy and childhood by contrast fistulography, ultrasound and CT. AB - From 1981 to 1989 seventeen cases of pediatric patients with urachal remnants have been treated at the Fukuoka Municipal Children's Hospital (2 patent urachus, 5 urachal cyst, 9 urachal sinus, 1 urachal diverticulum). The cases of patent urachus were discovered in the neonates due to a urine discharge from the umbilicus; in the older children, cysts or sinuses accompanied by an infection led to the diagnosis of the urachal anomaly. In 8 of 11 cases, fistulography established the diagnosis. In 9 of 12 cases, ultrasound imaging was diagnostically successful, as was CT in all 3 cases that were given scans. PMID- 1891255 TI - Traumatic aortic rupture in the pediatric population. Role of plain film, CT and angiography in the diagnosis. AB - A retrospective review was undertaken to determine the incidence of, and radiologic findings associated with aortic rupture resulting from blunt chest trauma in children. Records and imaging data of 54 consecutive pediatric patients admitted over a 2 year period to a pediatric trauma center after sustaining blunt chest trauma were reviewed. Four of 54 (7.4%) had a documented aortic tear. Plain films were evaluated for 7 radiographic signs described in the adult literature as sensitive indicators of aortic rupture, including abnormal aortic contour and mediastinal widening. Two groups of patients were defined: Group 1 (n = 4) had aortic rupture confirmed by angiography or operation and Group 2 (n = 50) with no angiographic investigation. All patients in Group 1 demonstrated mediastinal widening and abnormal aortic contour; however, 50 percent of patients in Group 2 had similar findings. Computed tomograms of the thorax where obtained were reviewed, including 1 patient from Group 1 and 6 patients from Group 2. The aortic tear was well demonstrated in the one patient from Group 1; however, the remaining computed tomograms were deemed inadequate for reliable exclusion of significant aortic injury. Plain chest radiographic findings in 5 consecutive children who underwent aortography in the two years subsequent to this series, including 2 additional patients with aortic rupture, were also reviewed, with similar results. In conclusion, traumatic aortic rupture in the pediatric population may be more common than previously reported. Plain film findings of aortic rupture in children are similar to those in adults, and are sensitive but non-specific. Currently, at least in our institution, this injury may be underinvestigated. Angiography remains the modality of choice in the diagnosis of aortic tears in children.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1891257 TI - The clinical usefulness of teleradiology of neonates: expanded services without expanded staff. AB - Teleradiology was utilized to link an offsite, high-risk nursery to the Department of Pediatric Radiology of Children's Hospital of Michigan. Interpretations via teleradiology were made in 4200 examinations and taken as the final reading. There was no expansion of either professional or technical personnel at either hospital to accomplish these ends. During the initial 3 months of the study, 40% of the teleradiographic images were double-read to evaluate the accuracy of the technique. During the subsequent 9 months, 17% of the cases were double-read, for an overall double-reading of 23%. There was a 98% agreement between the interpretations made using teleradiology and those made using hard copy. In no instances of the 2% (20 cases) in which there was disagreement between readings did the difference have clinical significance. Our results indicate that teleradiology linkage for interpreting neonatal examinations serves as a valuable tool for expansion of subspecialty expertise, allows more expedient recognition of abnormalities in the neonate, and facilitates faster transport to the appropriate tertiary care center. PMID- 1891256 TI - Magnetic resonance imaging of the pediatric airway. Compared with findings at surgery and/or endoscopy. AB - Evaluation of the pediatric airway is often complex and may require multiple imaging techniques and invasive procedures. We performed magnetic resonance (MR) imaging of the airway in 34 children with clinical evidence of chronic airway obstruction and compared MR findings with those obtained by surgery and/or endoscopy. MR diagnoses included vascular compression in 15 patients, primary tracheomalacic states in 12 patients, and mediastinal masses in 4 patients. Findings were normal for 3 patients. The MR findings were in agreement with the endoscopic findings in 25 of 28 cases and in agreement with the surgical findings in 21 of 21 cases. We conclude that MR imaging is a useful diagnostic tool in the evaluation of the pediatric airway because it may provide a specific diagnosis while obviating the need for more invasive studies. PMID- 1891258 TI - Comparison of a PACS workstation with conventional film for interpretation of neonatal examinations: a paired comparison study. AB - The diagnostic value of neonatal examinations using picture archiving and communication systems (PACS) was compared with that of conventional radiographs. A total of 202 consecutive chest or abdominal radiographs from the newborn intensive care unit were digitized for display on a commercially available PACS console. Experimental design was a paired comparison study. Plain films and PACS images were reviewed alternately in unbiased fashion. After the examination was evaluated using the second modality, any change in diagnosis or confidence in diagnosis was noted. Overall evaluation showed slight preference for the PACS modality. Change of diagnosis or in confidence of diagnosis was more than twice as likely to occur with evaluation of PACS (35%) after hardcopy than with evaluation of conventional radiographs (14%) after PACS. Of the variety of image processing features available on PACS, only window and leveling were judged to be of significant value. These results indicate that PACS and conventional radiographs of the neonatal chest and abdomen are of similar diagnostic value. PMID- 1891259 TI - Are hydrostatic and pneumatic methods of intussusception reduction comparable? AB - The hydrostatic pressures and flow rates of barium sulphate and water soluble contrast in concentrations representative of those used for intussusception reduction were measured. The change of height with discharge of fluid from the filled kit was also assessed. A group of experienced paediatric radiologists and radiographers significantly underestimated the height to which contrast should be placed for intussusception reduction. The results indicate that baseline hydrostatic reduction pressures tend to be less and maximum pressures significantly less than those presently advocated for pneumatic reduction. This disparity may account for the apparent improvement in intussusception reduction rates reported for air enema when compared with barium enema. Intraluminal pressure monitoring during contrast enema would aid control of intussusception reduction but hydrostatic reduction would still be at a disadvantage because of lower flow rates. Where hydrostatic reduction is performed, the contrast density and height used should be set to give known pressure, according to local guidelines. PMID- 1891260 TI - Ultrasonographic detection of free peritoneal fluid in uncomplicated intussusception. AB - Two cases of intussusception with free peritoneal fluid detected by ultrasound are presented. In neither of these cases was the fluid associated with perforation or intestinal compromise. After assessing the findings in these patients, we believe that small amounts of fluid may well be present in uncomplicated intussusception. Furthermore, we feel that its presence should not constitute a contraindication to nonsurgical reduction if no associated clinical findings to suggest perforation or intestinal compromise are present. PMID- 1891261 TI - Colonic diverticulitis in young patients with chronic renal failure and transplantation. AB - The association of colonic diverticulitis with chronic renal failure is well known. In those patients with "adult" autosomal dominant polycystic kidney disease, colonic diverticulitis is an especially common complication. We present two young patients (one teenager and one mid-twenties) who developed intra abdominal abscess several years after renal transplantation. Neither patient had autosomal dominant polycystic disease nor a known history of gastrointestinal problems but both proved to have underlying, previously unsuspected colonic diverticular disease with abscess formation. PMID- 1891262 TI - Multiple gastrointestinal atresias: sonography of associated biliary abnormalities. AB - The pre-operative finding of biliary ductal dilatation in the setting of multiple gastrointestinal atresias has not been previously reported. This paper illustrates the sonographic findings in two neonates with multiple gastrointestinal atresias from the prepyloric region to the rectum. Biliary ductal dilatation was seen in both patients and highly echogenic, mobile intraluminal bowel debris secondary to calcified meconium was evident in one. Post-operative biliary gas was demonstrated on sonography in one case. PMID- 1891263 TI - Unusual presentation of perforation of the gallbladder. AB - Perforation of the gallbladder is a known sequela of acalculus cholecystitis or trauma. A perforated gallbladder may be acute or chronic and can present with vague symptoms making the diagnosis difficult. With delayed recognition there is increased morbidity and mortality. The preoperative diagnosis requires an awareness of the symptoms and signs of acalculus cholecystitis as well as factors that predispose to the development of the diseased gallbladder. Awareness of the radiographic findings associated with a perforated gallbladder and acalculus cholecystitis is also important. The following is a case report of a child with a perforated gallbladder with a radiographic presentation not previously described. A review of the clinical pathogenesis and reported radiographic findings is also included. PMID- 1891264 TI - Pneumatosis intestinalis in two infants with rotavirus gastroenteritis. AB - Pneumatosis intestinalis is uncommon in children other than in the premature infant with necrotizing enterocolitis (NEC). We recently observed pneumatosis intestinalis in two infants with rotavirus gastroenteritis. Both children prior to the onset of acute vomiting and diarrhea were healthy and thriving with no evidence of any underlying illness. The disease and the pneumatosis intestinalis observed in the infants presented in this paper responded well to supportive and conservative medical management. The association of pneumatosis intestinalis in otherwise healthy children with acute rotavirus gastroenteritis has not been previously described. PMID- 1891265 TI - Calcific discitis: MRI changes in discs without visible calcification. PMID- 1891266 TI - Hangman's fracture or primary spondylolysis: a patient and a brief review. AB - Recognizing cervical fractures in the younger patient is often difficult. Potential fractures may look like congenital lesions or normal uncalcified synchondroses. We report a three month old infant with a subtle hangman's fracture which might have been confused with primary spondylolysis. The traumatic nature of the defect was confirmed by serial plain films and CT. In addition to showing the value of serial studies, we believe that this is the youngest confirmed case of hangman's fracture reported to date. The literature is reviewed. PMID- 1891267 TI - Wolf syndrome. AB - Since the initial description in 1965 of Wolf syndrome, or deletion of the short arm of chromosome number four, over one hundred cases have been reported. Much less, however, has been published on the radiologic findings in this disorder. We report a case with both typical and unusual features of the 4p- syndrome, including "bottle opener" deformity of the clavicles, and review the relevant literature. PMID- 1891268 TI - Infantile spasm induced by hemispheric pachygyria ultrasound, MRIand Tc-99m HMPAO SPECT. AB - We report a case of infantile spasm induced by hemisphere pachygria in which ultrasound and MRI provided precise anatomic information of hemisphere pachygria and Tc-99m HMPAO SPECT scintigraphy supplied an accurate assessment regional cerebral blood flow of infantile spasm during a seizure. PMID- 1891269 TI - Sonography of intracranial air in a newborn with meningomyelocele. AB - A newborn with an open meningomyelocele and intracranial air is described. Transfontanellar sonography allows initial detection of the unusual and previously undocumented finding of intracranial air associated with spinal dysraphism. PMID- 1891270 TI - Laryngotracheobronchial cartilage calcification in children. A case report and review of the literature. AB - Calcification of the upper respiratory tract is exceptional in persons aged under 15 years, and only 9 cases have been published so far in the English or French literature. We present a new case and analyse those already reported. PMID- 1891271 TI - A case of gastric duplication cyst with aberrant pancreas. AB - The radiographic and computed tomographic findings of a gastric duplication cyst contiguous to the stomach first diagnose in a 13-year-old-woman are presented. She revealed pyloric stenosis and chronic relapsing pancreatitis. In the smooth muscle wall and the connective tissue of the cyst lay aberrant pancreatic tissue and large neural bands. PMID- 1891272 TI - Stress fracture of the fibula in the first decade of life. Report of eight cases. AB - Stress fracture of fibula in athletes and ballet dancers is a well recognised entity. Fibular fractures in children in the first decade of life who are not active in sport or ballet dancing are not well known and often diagnosed as osteomyelitis or malignant bone tumour. This misdiagnosis may be followed by CT, nuclear scan or MR. All these investigations are not necessary and biopsy if performed might even be misleading. The plain X-rays show diagnostic radiographic findings and a misdiagnosis is highly unlikely especially when they are evaluated in the context of clinical findings. PMID- 1891273 TI - Disseminated BCG-osteomyelitis in congenital immunodeficiency. AB - A 9 month old female infant, who had BCG vaccination postnatally, was found to have severe combined immunodeficiency. She developed extensive disseminated skeletal osteomyelitis. Radiological studies showed numerous radiolucent lesions without reactive changes. PMID- 1891274 TI - Differences in the effects in the newborn piglet of various nonsteroidal antiinflammatory drugs on cerebral blood flow but not on cerebrovascular prostaglandins. AB - To characterize the role of prostaglandins (PG) in the regulation of basal cerebral blood flow (CBF) in the newborn, we determined the effects of four nonsteroidal antiinflammatory drugs, indomethacin (3 mg/kg, n = 8 and 10 mg/kg, n = 5), aspirin (65 mg/kg, n = 6), ibuprofen (30 mg/kg, n = 8), and naproxen (15 mg/kg, n = 6), on CBF, cerebral metabolism, and cerebrovascular PG in conscious 1 to 3-d-old piglets. Drugs and vehicle (n = 8) were injected i.v., and measurements were made 5 min before and 20 and 60 min after injections. Neither the vehicle nor any of the nonsteroidal antiinflammatory drugs exerted significant effects on mean arterial blood pressure and on blood gases and pH. All four drugs, with the exception of indomethacin at the lower dose (3 mg/kg), decreased PG to nearly undetectable levels within 20 min; the low dose of indomethacin caused a small decrease (18-32%) in PG at 60 min. However, the effects of these agents on CBF were diverse. CBF increased after the administration of aspirin, decreased to almost the same extent after both low and high doses of indomethacin, and did not change after the administration of ibuprofen and naproxen. Cerebral metabolic rate for oxygen was increased by aspirin but was unaltered by the other drugs. The data suggest that PG may not play a critical role in the regulation of basal CBF in the newborn animal and that certain nonsteroidal antiinflammatory drugs may have additional actions unrelated to the inhibition of PG synthesis. PMID- 1891275 TI - Postnatal changes in pyridine nucleotides in rat hepatocytes: composition and O2 dependence. AB - Postnatal changes in pyridine nucleotide concentration, composition, and oxidation-reduction characteristics were studied in liver cells from neonatal (newborn, d 4 and d 8) and adult rats to determine the development of hepatic pyridine nucleotide status and O2 dependence of oxidation of reducing equivalents. The results show that the total pyridine nucleotide concentrations in newborn and 4-d-old rat liver were low (30%) but increased to near adult values (80%) by d 8 postpartum. Analyses of the cellular distribution of NAD+, NADH, NADP+, and NADPH reveal that the reduced forms (NADH plus NADPH) accounted for over 50% of the total in the newborn and 4-d-old rats compared to 30% in adult animals. This relatively higher reductive capacity in hepatocytes of younger rats was largely the result of a significantly higher proportion of NADPH in these cells. Examination of the NADPH/NADP+ and NADH/NAD+ ratios show that they occur in an inverse relationship with postnatal age; the NADPH/NADP+ ratio was high at birth and decreased with age, whereas the reverse pattern was found for the NADH/NAD+ ratio. The result, that NADPH represents a significant percentage of the total pyridine nucleotides in neonatal cells in the early postnatal period, is consistent with a higher demand for NADPh for biosynthetic activities in association with tissue growth.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1891276 TI - The role of C3 in mediating binding and ingestion of group B streptococcus serotype III by murine macrophages. AB - To understand how complement effects phagocytosis of type III group B streptococcus, we assessed the specific role of C3 in mediating binding and ingestion of these bacteria by macrophages. Phagocytosis of bacteria by resident mouse peritoneal macrophages was measured under conditions in which C3 deposition on bacteria was inhibited or after blockade of C3-ligands or of complement receptor type three (CR3) with specific antibodies. C3 depletion, incubation with F(ab')2 fragments of antibody to C3, or blockade of CR3 completely inhibited the binding of bacteria that was seen in the presence of nonimmune serum. Immune serum increased the number of associated organisms 6-fold compared to that seen with nonimmune serum. With this serum, 82% of organisms were ingested. C3 depletion or CR3 blockage had a modest effect, but this interaction could be ablated completely only after Fc receptors were blocked. Using varied concentrations of an IgG2a MAb against type III capsular antigen, it was possible to show that small amounts of antibody incapable of mediating bacterial binding by itself directed an interaction that also depended upon C3. Phagocytosis of group B streptococci by macrophages in the presence of little or no antibody requires complement and C3 opsonization specifically. C3-dependent binding may be important in determining mononuclear phagocyte-dependent clearance of these pathogens from blood, particularly in patients with little or no type-specific serum antibody. PMID- 1891277 TI - In vitro induction of IgG1 and IgG2 secretion by B cells of children who developed invasive haemophilus disease despite vaccination. AB - Lymphocytes from seven patients who developed Haemophilus influenzae type b (Hib) disease after being vaccinated with Hib polysaccharide vaccine and from one patient who developed disease after conjugate vaccination were investigated for the ability to secrete IgG1 and IgG2, in vitro, in response to a combination of pokeweed and Staphylococcus aureus Cowan I mitogens. The eight patients were selected because they had low anticapsular antibody responses to Hib disease. Only one of the eight children had a history of previous severe, recurrent infections. This child (in whom a polysaccharide vaccine failed) had a deficiency of the second component of complement and also had a subnormal serum concentration of IgG4. Only one of the eight children, an otherwise healthy 54-mo old with normal serum Ig concentrations, had subnormal mitogen-induced B-cell secretion of IgG1 and/or IgG2. When this child's lymphocytes were separated into T- and B-cell fractions and cocultivated with the respective fractions of the father's lymphocytes, the child appeared to have an intrinsic B-cell defect and normal T cells. There were no significant differences (p greater than 0.3) in the respective geometric means of the in vitro secretion of IgG1 or IgG2 of the B cells from the children with polysaccharide vaccine failure and those of 14 healthy controls of similar ages as the patients (IgG1, 1524 versus 3497 ng/mL per 10(5) lymphocytes; IgG2, 79 versus 89 ng/mL per 10(5) lymphocytes). Thus, despite the presence of impaired serum anticapsular antibody responses to Hib disease, most children who develop Hib disease after Hib polysaccharide vaccination have normal in vitro B-cell secretion of IgG1 and IgG2 in response to mitogens. PMID- 1891278 TI - Leucine kinetics during feeding in normal newborns. AB - To examine how leucine and protein metabolism is affected by feeding, leucine kinetics were determined in 11 normal term newborns during feeding using a prime constant tracer infusion of 1-13C leucine combined with respiratory calorimetry. Fed newborns were compared with previously studied fasting newborns. Feeding and fasting newborns had similar rates of leucine oxidation (34 +/- 3 mumol/kg/h versus 31 +/- 4 mumol/kg/h) and leucine release from existing protein (156 +/- 16 mumol/kg/h versus 164 +/- 8 mumol/kg/h). In contrast, nonoxidative disposal rates of leucine (a reflection of protein synthesis) were significantly greater in feeding newborns (170 +/- 13 mumol/kg/h versus 129 +/- 9 mumol/kg/h). A significant positive correlation between birth weight and leucine flux was demonstrated in both feeding and fasting newborns. These results suggest that 1) newborns may accomplish protein accretion primarily by increases in protein synthesis rather than suppression of protein breakdown; 2) an estimate can be made of the minimal leucine intake required to replace irreversible leucine oxidative losses (816 mumol/kg/d, 107 mg/kg/d); and 3) the positive correlation between birth weight and leucine flux in both feeding and fasting newborns may be a result of differences in previous protein and energy supplies. PMID- 1891279 TI - Somatosensory evoked potentials in neonates with primary congenital hypothyroidism during the first week of therapy. AB - At the present, the influence of intrauterine hypothyroidism on the fetus is estimated by bone age (BA). BA is also used as a predictor of later neuropsychologic development. The aim of this study was to investigate whether the neurophysiologic maturation of neonates with congenital hypothyroidism (CHT) is delayed at the start of therapy and, if so, whether this delay is comparable to that in BA. Twenty-seven infants with CHT were examined with median nerve somatosensory evoked potentials (SEP) before or within 1 wk after initiation of therapy. The effect of neonatal jaundice, a potential confounder of neonatal SEP, was also evaluated. Cervical (N13), first cephalic (N19), and second cephalic (N32) peak latencies were measured, as well as N13-N19 interval (central conduction time) and N13 latency divided by arm length. The SEP data of 103 normal infants were used as reference values. In the CHT newborns, a maturational delay was found for all SEP parameters. Preterm infants (n = 3) were conspicuously less affected than term patients. In term CHT infants, jaundice during the first postnatal week, but not late jaundice, had an additional adverse effect. SEP delay was not related to initial or actual T4 levels. BA delay exceeded SEP delay by several weeks. Our data suggest that the depressed T4 levels of the hypothyroid fetus and neonate affect the nervous tissue to a lesser degree than bone tissue and, further, that SEP is superior to BA as parameter for the evaluation of neurologic maturation of infants with CHT. PMID- 1891280 TI - Evaluation of insulin sensitivity in obese offspring of diabetic rats by hyperinsulinemic-euglycemic clamp technique. AB - Young adult macrosomic offspring of streptozotocin-induced mildly hyperglycemic rats exhibit accelerated growth through the first 10 wk of age. At 10 wk, oral glucose loading resulted in elevated plasma insulin and glucose concentrations compared to controls. To assess the mechanism of the abnormal glucose tolerance in vivo, hyperinsulinemic-euglycemic clamp studies were performed. Ten-wk-old rats were fasted overnight, and porcine insulin was infused (2.4 mU.kg-1.min-1). Glucose was infused concurrently at varying rates to maintain euglycemia for 40 60 min. Insulin levels were raised from a baseline value of 163 +/- 57 pmol/L (23 +/- 8 microU/mL) (SD) to 476 +/- 57 pmol/L (67 +/- 8 microU/mL) at steady state for males and from 178 +/- 43 pmol/L (25 +/- 6 microU/mL) to 454 +/- 43 pmol/L (64 +/- 6 microU/mL) for females. The results showed that the macrosomic male and female animals were significantly less sensitive to the effects of insulin than were their respective controls; this was evident by a lower increment in glucose disposal rate per unit increase in insulin (0.04 +/- 0.01 versus 0.11 +/- 0.03 for males and 0.05 +/- 0.03 versus 0.18 +/- 0.07 mg.kg-1 per microU/mL for females). The endogenous glucose production by the liver in the basal (fasted) state in the macrosomic group compared to controls was higher, suggesting possible hepatic insulin resistance. However, endogenous glucose production was suppressed to the same degree between the experimental and control groups during the hyperinsulinemic period, suggesting that the hepatic insulin resistance can be overcome by high insulin levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1891281 TI - Substrate utilization for phosphatidylcholine synthesis by type II pneumocytes of neonatal rats. AB - Type II pneumocytes isolated from neonatal rat lungs, using an isolation procedure developed for adult rats, were found to be phenotypically stable and metabolically active in culture. The cells, purified by metrizamide gradient centrifugation and differential adherence, were capable of synthesizing phospholipids from 14C-labeled choline, palmitate, glucose, and acetoacetate. Regardless of the 14C-labeled substrates used, greater than two thirds of the radioactivity incorporated into phosphatidylcholine was recovered in disaturated phosphatidylcholine, the major component of surfactant phospholipids. The incorporation of palmitate into phosphatidylcholine and other phospholipids (i.e. phosphatidyl-ethanolamine, -glycerol, -serine, and -inositol) indicates that the neonatal type II cells have the capacity to produce surfactant lipids. The neonatal cells preferentially utilized acetoacetate over glucose as a precursor of phospholipids. In the adult type II cells, glucose was incorporated into phospholipids more rapidly than acetoacetate. The rate of glucose incorporation in the neonatal cells was enhanced by exogenous insulin. The preferential utilization of acetoacetate by the neonatal type II cells is consistent with the stimulated acetoacetyl CoA synthetase pathway in the lung. The depressed glucose incorporation into phospholipid, on the other hand, may be attributed to insulin insufficiency in the neonate. PMID- 1891282 TI - Prostaglandin inhibition prevents the fall in pulmonary vascular resistance as a result of rhythmic distension of the lungs in fetal lambs. AB - Prostaglandins (PG) are vasoactive factors involved in the regulation of pulmonary vascular resistance at birth. However, their physiologic importance is unclear. We hypothesized that PG are important regulators of pulmonary vascular resistance during static and rhythmic distension of the lungs. To test this hypothesis, we studied seven near-term fetal lambs treated with meclofenamate (a PG synthetase inhibitor) and six controls. The fetal lambs were instrumented on a long-term basis with vascular catheters to measure pulmonary arterial pressures, left atrial pressures, and pulmonary blood flow (radionuclide-labeled microsphere method). The fetal airway was intubated, and the ductus arteriosus wall was infiltrated with formalin to assure full patency during the study period. Pulmonary vascular resistance was calculated during baseline and during sequential in utero static distension of the fetal lungs, rhythmic distension, and ventilation with oxygenation. We found that during rhythmic distension, inhibition of PG synthesis abolished the 4-fold decrease in pulmonary vascular resistance seen in the control group. In contrast, during static distension, pulmonary vascular resistance did not change in either group, and during ventilation with oxygenation, pulmonary vascular resistance decreased 12-fold in both groups. We conclude that PG are important regulators of pulmonary vascular resistance during rhythmic distension but are not essential for the regulation of pulmonary vascular resistance during static distension or during ventilation with oxygenation. PMID- 1891284 TI - Cardiovascular and respiratory response to static exercise in the newborn kitten. AB - Muscle contraction produces a reflex increase in blood pressure, heart rate, and minute ventilation in adults. To evaluate the role of this reflex in newborns, we compared the blood pressure, heart rate, and ventilatory responses to static contraction of the hindlimb muscles in sedated newborn and adult felines. The reflex response to muscle contraction was compared with the baroreflex, the chemoreceptor reflex, and the response to maximal stimulation of sciatic nerve afferents. With muscle contraction, newborn systolic blood pressure increased by 8.5 +/- 2.6%, which was significantly less than the adult response of 15.9 +/- 1.8% (p less than 0.025). Heart rate response to muscle contraction was less in newborns compared with adults, increasing by 1.4 +/- 0.5 and 8.3 +/- 1.3%, respectively (p less than 0.025). In contrast to heart-rate and blood-pressure responses, ventilatory responses to muscle contraction were similar in both age groups, increasing by 34 +/- 20 and 34 +/- 10% in newborns and adults, respectively. With stimulation of sciatic nerve afferents and with hypoxemia, blood pressure and heart rate increased similarly in both newborns and adults. When the baroreflex was elicited, heart rate decreased similarly in both age groups. We conclude that newborn cats have a reduced heart rate and blood pressure response to muscle contraction compared with the adult. We speculate that the postnatal development of this reflex is due to maturation of integrative and modulatory mechanisms in the CNS. PMID- 1891283 TI - Calcium current measurements in acutely isolated neonatal cardiac myocytes. AB - Action potentials and voltage clamp-induced ionic currents were recorded in acutely isolated neonatal rabbit cardiac myocytes using the whole-cell voltage clamp technique. Time- and voltage-dependent Ca2+ currents in neonatal myocytes were elicited by depolarizations from a holding potential of -80 mV to various clamp potentials. The maximal measured inward Ca2+ current was 206 +/- 10 pA (mean +/- SEM, n = 51). The peak current occurred at a mean membrane potential of 7.8 +/- 1.3 mV (n = 51). The Ca2+ current voltage relation was shifted 26 mV in the positive direction when the external Ca2+ concentration was increased 10 fold. Ca2+ current rundown was observed with a half-time of approximately 20 min. Cells dialyzed with solution containing the Ca2+ chelating agent, EGTA (0.04 mM), had action potential durations similar to those previously reported in papillary muscle. In contrast, a higher concentration of EGTA (14 mM) prolonged the action potential duration. Control of the cell internal ionic composition was achieved by dialysis of the cell with a time constant for Na+ ions of 1.2 to 2.6 min. Tetrodotoxin (10 microM), included in some experiments to block Ca2+ entry via Na+ channels, was shown to be more than 98% effective. These results characterize the whole-cell voltage clamp technique as applied to immature heart cells. PMID- 1891285 TI - Antigenuria after immunization with Haemophilus influenzae oligosaccharide CRM197 conjugate (HbOC) vaccine. AB - We tested the urine of 30 infants 6 weeks to 7 months of age after they received standard 10-micrograms (0.5-ml) doses of HbOC (HibTITER) Haemophilus influenzae b (Hib) conjugate vaccine for the presence of Hib antigenuria using a commercially available latex particle agglutination assay (Directigen). Urines were collected within 1 hour, from 1 to 3 hours, at 24 hours and at 3, 6 and 9 days after vaccine administration and reactions were quantitated from 0 to 3+. In contrast to previous studies in older children which showed little or no antigenuria following HbOC vaccination, our study shows that in infants intense Hib antigenuria is evident within 2 to 3 hours and persists 3 days after vaccine administration and that less intense antigenuria may be detected in some infants for several days. With efficacious vaccines now being used in 2- to 6-month-old infants, invasive Hib disease may soon be limited to infants of this age just before their seroconversion. It should be recognized that antigenuria occurs for several days after vaccination with Hib conjugate vaccines and that it could be erroneously interpreted as evidence of invasive Hib infection. PMID- 1891286 TI - Persistence of serum antibodies elicited by Haemophilus influenzae type b-tetanus toxoid conjugate vaccine in infants vaccinated at 3, 5 and 12 months of age. AB - Eighty-five children received three injections of a vaccine consisting of Haemophilus influenzae type b (Hib) capsular polysaccharide (CPS) conjugated to tetanus toxoid (TT) (Hib-TT) at 3, 5 and 12 months of age according to the vaccination schedule for Swedish children. Diphtheria-tetanus toxoid vaccine was concurrently injected at another site. Two dosages, 7.5 and 15 micrograms, of Hib CPS were studied. No serious reactions occurred. Hib-TT elicited fewer local reactions than diphtheria-tetanus toxoid vaccine. Significant increases in Hib CPS serum antibodies occurred after all injections in both dosage groups with virtually no differences between the two groups. After the first and second injections geometric mean serum antibody concentrations of both dosage groups combined increased to 0.49 and 3.71 micrograms/ml and 81 and 99% of the vaccinees, respectively, had concentrations greater than 0.15 micrograms/ml. After the third dose geometric mean concentrations increased to 13.7 micrograms/ml and all had concentrations greater than 0.15 micrograms/ml. The geometric mean Hib CPS antibody concentrations decreased to 1.24 micrograms/ml 18 months after the third injection, but 97% still had concentrations greater than 0.15 micrograms/ml. The rise of Hib CPS antibodies was mostly in the IgG class. The most pronounced increase was seen in the IgG1 subclass but there were also increase in IgG2 and IgG3. Protective concentrations of TT antibodies were found in all postimmunization sera. In conclusion Hib-TT is safe and immunogenic in infants and should be protective from 6 to 30 months and probably longer thereafter. PMID- 1891287 TI - Community- and hospital-acquired respiratory syncytial virus infections in Chile. AB - Nasopharyngeal aspirates were obtained on admission from 614 patients younger than 2 years of age who were hospitalized in a ward for acute respiratory infections from June 1988 through October, 1989, in Santiago, Chile. Patients in two rooms were followed during the cold seasons by sampling aspirates every other day during the child's entire hospital stay. Clinical features were recorded daily. Indirect monoclonal immunofluorescent assay and isolation in HEp-2 were used for respiratory syncytial virus (RSV) diagnosis. The mean RSV detection rate was 39% at the time of admission, ranging from 8% in April, 1989, to 62% in July, 1988. During the cold months 43 of 288 (15%) nosocomial RSV cases were detected. Pneumonia and wheezing bronchitis were the principal diagnoses of both groups admitted, whether they were shedding RSV or not. It is concluded that RSV plays a major role in admissions for acute respiratory infections, as well as in nosocomial infections, in Santiago. Because clinical features do not allow one to differentiate viral from bacterial acute respiratory infections, the importance of rapid viral diagnosis is emphasized. PMID- 1891288 TI - Recurrent varicella-zoster virus infections in apparently immunocompetent children. AB - Fourteen generally healthy children (5 females, 9 males, ages 18 months to 13 years) who have developed 2 to 5 attacks of chickenpox are described. Herpes zoster also occurred in 2 of 14 children. No case of chickenpox was severe or associated with complications. General studies of immunoglobulins, specific antibodies to immunization agents, complement and lymphocyte subpopulation number and function indicated that 1 of 14 had low serum IgA and 3 of 14 lacked antibody to 1 (n = 2) or 2 (n = 1) immunization agents. Varicella-zoster virus (VZV) specific immune studies showed that the children developed VZV-antibody titers by enzyme-linked immunosorbent assay of 1:640 to 1:10 240. By immunoblot assay all appeared to develop a normal spectrum of antibodies to individual VZV proteins. All but one developed VZV cellular immune responses with stimulation indices ranging from 3.6 to 174. Sequential follow-up of 8 patients revealed 1 who became seronegative and 2 who lost VZV cell-mediated immune responses. Chickenpox may recur more frequently than is generally recognized. General and VZV-specific immune investigations are unlikely to indicate a reason. PMID- 1891289 TI - The influence of preschool pertussis immunization on an epidemic of pertussis. AB - Between 1988 and 1989 there were 896 reported cases of pertussis in Arizona. Of the 781 investigated cases 55 were identified in children younger than 5 years of age. Thirty-five percent of children between 6 months and 5 years of age were not fully immunized; 3 infants died. Approximately 50% of infected children between 5 and 14 years of age had not received 5 doses of pertussis vaccine. Of the 413 physician respondents to a questionnaire, fully 10% do not administer pertussis vaccine to preschool children because of parental, personal or other reasons. We hypothesize that the reservoir of pertussis-susceptible older children and young adults is augmented by this omission of the fifth diphtheria-tetanus toxoids pertussis vaccine. Newer educational and vaccine strategies are necessary to prevent epidemics of pertussis. PMID- 1891290 TI - Haemophilus influenzae causing conjunctivitis in day-care children. AB - The role of Haemophilus influenzae in acute purulent conjunctivitis was studied during an outbreak among children in day care. Five day-care centers contributed 20 cases and 35 controls. All the children were subjected to culture of the nasopharynx and the eyes. H. influenzae was carried in the nasopharynx of 53% of the children (range between day care centers, 20 to 91%). Of the 20 children with acute conjunctivitis 8 had eye cultures positive for H. influenzae, 2 had Moraxella and the remaining were culture-negative. Ten colonies of H. influenzae were isolated from each positive culture and identified by capsular type, biotype and multi-locus enzyme electrophoresis. All but one of the isolates were nonencapsulated. They belonged to 4 biotypes and 8 electrophoretic types. The same strain was recovered from the eyes and nasopharynx of the symptomatic children, suggesting that the H. influenzae in the eyes originated from the nasopharynx. There was no evidence for spread of the same H. influenzae strains between day-care centers. Even within each center the Haemophilus strains recovered from the eyes varied among the symptomatic children. The in vitro capacity to attach to oropharyngeal epithelial cells was not increased among the H. influenzae recovered from the eyes. The results question if the majority of conjunctivitis cases were caused by H. influenzae and suggested that eyes were colonized with the nasopharyngeal carrier strain rather than infected by an isolate with special virulence for the eye. PMID- 1891291 TI - Immunodeficiency in the 1990s. PMID- 1891292 TI - Ciprofloxacin in neonates and its possible adverse effect on the teeth. PMID- 1891293 TI - Protection against Plasmodium falciparum infection in children with hemoglobin S. PMID- 1891294 TI - Group B streptococcal disease in twins: failure of empiric therapy to prevent late onset disease in the second twin. PMID- 1891295 TI - Acute vs. recurrent pharyngitis. PMID- 1891296 TI - Prolonged headache and fever in a 19-year-old with Blackfan-Diamond syndrome. PMID- 1891297 TI - Concurrent congenital human immunodeficiency virus infection and toxoplasmosis. PMID- 1891298 TI - Prolonged fever in tuberculosis. PMID- 1891299 TI - Role of oral bacteria. PMID- 1891301 TI - Vitamin A therapy in infectious diseases. PMID- 1891300 TI - Radiographic diagnosis of sinusitis in children. PMID- 1891302 TI - Accurate knowledge about suicide and judgments about suicide. PMID- 1891303 TI - Preferred sound intensity increase for sensation of half distance. AB - Two experiments are reported that examine the preferred increase in intensity for creating a percept of half auditory distance from a reference. The results of both experiments indicate that the use of an inverse square law (increments of 6 dB) is not the best signal-processing method for this purpose. The application of the results is potentially useful towards the software design of 3-D auditory display systems that manipulate the perceived distance of auditory inputs in relationships to actual distances of physical objects. PMID- 1891304 TI - Mortality from suicide in attempted suicides. PMID- 1891306 TI - Alexithymia, depression, and suicidal preoccupation. PMID- 1891305 TI - An analysis of task difficulty using the visually degraded stimulus task. AB - This article discusses the utility of the Visually Degraded Stimulus Task developed in 1986 by Vokey, Baker, Hayman, and Jacoby. The program provides 30 line drawings than can be presented in complete form prior to receiving incomplete forms of the same or similar drawings. In the incomplete form, a small percentage of a drawing can be added with each touch of the computer space bar. By this means the percentage of drawing required for identification can be obtained. In this article, difficulty levels of incomplete picture identification are provided for each drawing under conditions of no previous viewing (no prime), previous viewing in an alternate form (conceptual prime), and previous viewing of the same drawings (exact prime). Modifications to the microprocessor computer program are provided to increase its usefulness as a means of testing priming effects in visual memory. Program applications are provided for the study of memory and neuropsychology. PMID- 1891307 TI - Perception of goal proximity, latency and duration of action plans, and worry in relation to goal distance in time and personality characteristics. AB - 128 male high school students were tested for achievement motives, future-time orientation and perceived intrinsic instrumentality, and answered several questions related to future goals or tests at different distances in time. Success-oriented individuals and individuals with high future-time orientation perceived the goals as closer, planned to initiate preparations for the goals earlier, and planned to devote more time in the preparation than failure-oriented individuals and those with low future-time orientation. Interactions of motives and future-time orientation on the perception of goal proximity and planned time of initiating goal preparations did also emerge. Motives and future-time orientation affected the dependent variables most when the goals were at some distance in time (i.e., 1 yr. and 3 mo.), and the effects were minimized for the goal relatively close in time (i.e., 1 wk.). Individuals with high instrumentality report that they would start preparations earlier, devote more time to all goal preparations, and perceive more worry for the goal closest in time than individuals with low instrumentality. In addition, interactions of motives and instrumentality and of future-time orientation and instrumentality are presented. The results are interpreted and discussed in relation to the dynamics of action theory of Atkinson and Birch and other theories of achievement motivation. PMID- 1891308 TI - Empathy, others-concept, and prosocial orientation. AB - The relationship between 56 nursing students' empathy and their others-concept was investigated to establish ties to a broader construct, prosocial orientation. The female Caucasian nursing students were rated for empathy by two clinical instructors. They were also given the Paired Hands Test to assess their others concept. The students with the higher empathy ratings had more positive others concepts. The responses of the low empathy group to the Paired Hands Test indicated a much stronger tendency to perceive and interpret social interactions negatively. Besides practical implications for nurses and other helping professionals, these findings have theoretical ramifications as well. Others concept has been shown previously to be related to a cluster of variables such as positive social behavior and moral judgment. Evidence of the relationship to empathy helps to tie this cluster to the prosocial orientation construct as a base for further research. PMID- 1891309 TI - Stability of correlations among ratings on concreteness, imagery, emotionality, and interest values when meaning is controlled. AB - We hypothesized that correlations among ratings on concreteness, imagery, emotionality and interest of words are high stable, independent of present ratings by the 32 boys, 80 girls, and 92 adolescents. PMID- 1891310 TI - Locus of control and alcohol placebo effects on performance in a driving simulator. AB - Performance in a driving simulator was evaluated as a function of locus of control, perceived alcohol ingestion (no alcohol versus a no-alcohol placebo), and sex. Using a pretest-posttest design, an analysis of covariance was performed using the pretest performance on a driving simulator as the covariate. There were 10 men and 10 women in each of four groups. As predicted, the external-scoring placebo subjects made more posttest errors than did the internal-scoring placebo group or either of the no-alcohol control groups. This indicated that the external-scoring placebo subjects were more affected by what they expected to happen than their actual physiological state warranted. A difference was also found in which external-scoring women made more errors than did any other group. This was an unexpected finding which, being inconsistent with previous findings involving sex, warrants further research. PMID- 1891311 TI - Blackness enhancement. AB - Since apparent brightness increases as an intermittent luminous source decreases from flicker fusion to approximately 10 cps, the phenomenal blackness induced by an intermittent annulus should also increase as a result of brightness contrast. However, data from 5 observers showed the phenomenal blackness occurring with a 10-cps inducer was greater than that expected on the basis of brightness contrast. PMID- 1891312 TI - Interscorer reliability for the Hand Test administered to children. AB - The utility of the Hand Test as a quick, reliable measure of 100 children's personalities was assessed. The interscorer reliability of the Hand Test was estimated by both intraclass correlations and the Kappa coefficient for 100 children. Following training, satisfactory intraclass correlations were obtained for the Quantitative scores (20 of 22 above .70) and Qualitative scores (12 of 27 above .70) Kappa coefficients were generally lower. Scorers' memory overload and low response frequency are discussed as possible bases for the low reliabilities of Qualitative scores. Although the Hand Test reliability for Quantitative scores is consistent with those of other projective tests, consideration should be given to the modification of the directions of administration for young children and clarification of scoring rules. PMID- 1891313 TI - Social anxiety and stuttering. AB - Social anxiety among 110 stutterers was compared with the measures of two control groups (110 social phobic patients and 110 normal persons). Results do not support the notion of social anxiety as an essential part of stuttering. PMID- 1891315 TI - The dimension of focussed attention: relationship to behavior and cognitive functioning in children. AB - A sample of 73 nonreferred school children were administered a newly developed Visual Focussed-attention Test along with other measures of attentional, cognitive, and behavioral functioning. Internal reliability and construct validity for the test were established. Children were then divided into underfocussed (distractible, n = 6), normofocussed (n = 38), and overfocussed (n = 5) groups based upon their test scores. The three groups did not differ with regard to age, intellectual functioning, or academic achievement. However, the underfocussed and overfocussed groups contained a greater proportion of behaviorally disturbed children than the normofocussed group. Underfocussed children, as a group, were rated higher than normofocussed, but not higher than overfocussed children on the Hyperactivity factor of the Conners Teacher Questionnaire. The significance of these focussed attention deficits is reviewed in relation to the more familiar concepts of distractibility and hyperactivity. PMID- 1891314 TI - Cognitive and motor deficits in selected unilateral brain-injured patients. AB - 16 right hemisphere and 16 left hemisphere, nonaphasic brain-injured stroke patients were compared with 16 matched normal controls on the verbal and visuospatial paired-associate tasks developed by Stark in 1961 as a partial replication to a more severely impaired population. Right brain-injured patients showed a significant visuospatial deficit and contralateral motor impairment; while left brain-injured patients, screened for aphasia, showed contralateral motor impairment but did not show impairment on the verbal task. Examination of the areas of infarct resulting from the cerebrovascular accident in the left hemisphere patients suggested that the presence of a contralateral motor deficit without verbal impairment results from specific focal occlusions of branches of the middle cerebral artery in this selective group of patients. PMID- 1891316 TI - Activity level across the menstrual cycle. AB - 7 women recorded number of miles walked per day and oral temperature daily upon rising for 6 weeks. Analysis of variance indicated no significant differences in activity level associated with cycle phases but individual differences in activity level among subjects were significant. PMID- 1891317 TI - Cerebral asymmetry in dementia: effect of context on hemi-attention. AB - The duration of the orienting response toward the left or right hemispace as a function of bright light and noise levels was evaluated in 6 demented elderly patients. Tentative findings of cerebral asymmetry suggest light may differentially activate the left hemisphere. PMID- 1891319 TI - Ego strength denial on the MMPI-2 as a clue to simulation of personal injury in vocational neuropsychological and emotional distress evaluations. AB - Ego Strength (Es) scores on the MMPI-2 were compared for malingering and nonmalingering samples of personal injury claimants. These data suggest that the Es scale has utility in differentiating these two samples. A cut-off score of Es less than 31 is suggested for identifying personal injury malingerers in nonpsychotic outpatient population who are not obviously grossly disabled. Cross validation is recommended. PMID- 1891318 TI - Quantity of communicative behavior in children from birth to 30 months. AB - 68 normal children were observed during play interaction with their mothers. Children's communicative acts were coded according to form and function, based on seven levels of communicative competence. Seven age groups, corresponding to the developmental predominance of each, were formed from birth to 30 mo. Each included equal numbers of girls and boys. Total number of communicative acts were determined for each child. Girls produced significantly more communicative output than boys. Verbal children produced significantly more output than preverbal children. There were no significant differences between preverbal groups or between verbal groups. The results are discussed relative to other research. PMID- 1891320 TI - Latency of auditory event-related potential P3 correlates with forward Digit Span in an Alaskan subarctic sample. PMID- 1891321 TI - Adolescents' learning environments and aspirations: ethnic, gender, and social status group differences. AB - Discriminant analysis was used to examine relationships between social groups, defined jointly by ethnic group membership, gender, and social-status background, and measures of adolescents' perception of family and school learning environments and their educational and occupational aspirations. In the sample there were 400 16-yr.-old Australians from AngloAustralian, Greek, and Southern Italian families. The findings suggest that, if adolescents are classified in social groups defined by ethnicity, gender, and social status, then there are strong social-group differences in adolescents' perceptions of learning environments and in their aspirations. PMID- 1891322 TI - Structural equation analysis of an exercise/sleep health practices model on quality of life of elderly persons. AB - An exercise/sleep model from past research was tested for relationships with a quality of life measure of the health status of 126 elderly persons. Past statistical analyses of this relationship used canonical correlation statistical analyses. In the following study, when structural equation analysis (LISREL VII) was applied to the same data, an altered model resulted: an exercise-only model. To examine this relationship further, researchers should employ a longitudinal design with a more comprehensive model and larger sample of elderly persons. PMID- 1891323 TI - Concordance between two measures of dream bizarreness. AB - To assess the level of concordance between two published measures of dream bizarreness, 100 randomly selected dreams from 93 college students were scored for primary process using the Auld, Goldenberg, and Weiss scale and for dream distortion using Zepelin's scale. This analysis yielded a strong relationship between these measures, indicating adequate concurrent validity for the content analysis of the construct of dream bizarreness. PMID- 1891324 TI - Visual discrimination and visuomotor integration among two classes of Brazilian children. AB - The Raven Matrices, Beery, and Bender-Gestalt tests were given to 415 Brazilian children in public and private schools corresponding to two socioeconomic statuses. Both social class and grade in school influenced all scores more than age. The Raven Matrices appeared to be the most affected by social class differences. Visual-motor integration and visual discrimination skills were moderately (.47-.69) correlated, especially among the private school students. Maturational differences based on age and school grade were considered somewhat better assessed by the Beery than the Raven or Bender-Gestalt tests. The wide age range at each grade and the decreasing enrollment in higher grades makes interpretation difficult. PMID- 1891325 TI - The Geriatric Depression Scale and Hopelessness Index: longitudinal psychometric data on frail nursing home residents. AB - We administered the Geriatric Depression Scale and the Hopelessness Index 18 times over a 39-wk. period to an initial sample of 76 old, frail, multiply impaired, and depressed nursing home residents participating in a longitudinal quasi-experimental study on the effects of cognitive group interventions on cognition, depression , hopelessness, and life satisfaction. As no changes over time were observed on the outcome variables of geriatric depression and hopelessness, the stability of the instruments' internal consistency was examined longitudinally. For the Geriatric Depression Scale, Kuder-Richardson KR-20 coefficients ranged from .69 to .88, with a mean of .82 (SD = .05). Coefficients for the Hopelessness Index were between .72 and .86, with a mean of .80 (SD = .04). We conclude that both instruments give reliable measurements of geriatric depression and hopelessness in old, frail, and depressed nursing home residents. PMID- 1891326 TI - Recognition of nonexplicitly presented odors. AB - This research was designed to check to what extent naive subjects can recognize odors in a situation similar to those of daily life. The odors were presented nonexplicitly and without any warning to memorize them for a later recognition task. Different intensities of noise were used to verify whether these affect the olfactory recognition task by modifying arousal and check whether a situation made more unpleasant by a louder noise produces changes in subjects' evaluations of the pleasantness of the odors presented. Also, subjects' personality traits were measured on extraversion-introversion and self-monitoring questionnaires. The three odors (Eucalyptolus, linalile acetate, bornile acetate) were recognized just under 50% of the time and were recognized differently. The number of recognitions did not vary significantly by sex or noise conditions; the most intense noise affected only the number of false alarms. Pleasantness scores differed only among the different odors. High self-monitoring subjects tended to have fewer recognitions; scores on extraversion-introversion produced no significant effect. PMID- 1891327 TI - Effects of tryptophan depletion on Poggendorff illusion, corner Poggendorff illusion, and attention. AB - The effects of a tryptophan-free amino acid mixture on Poggendorff illusion, corner Poggendorff illusion, and attention were investigated with 12 male subjects who ingested either a balanced amino acid mixture or a tryptophan-free mixture, the latter known to cause a marked depletion of brain tryptophan and serotonin. No significant difference between the two mixtures on the perceptual illusions was found. PMID- 1891328 TI - The Defense Mechanism Test in nonpsychotic psychiatric outpatients and normal controls. AB - In the Defense Mechanism Test, stimuli representing a central figure threatened by a peripheral person are presented tachistoscopically, at increasing exposure times. The threat is assumed to trigger defense mechanisms that are expressed by several types of perceptual distortions. Given that to date no experimental study has validated the discriminative power of the Defense Mechanism Test between normal controls and clinical groups, 99 normal controls and 57 nonpsychotic psychiatric outpatients were given the test. Significantly more psychiatric patients than controls were coded for presence of each of the ten main defensive signs of the Defense Mechanism Test (with a peak significance for reaction formation). Ten codings or subcodings of defense which were particularly rare in the control sample were employed to discriminate between groups. This procedure correctly allocated 85.8% of the control subjects and 85.9% of the psychiatric patients. The present findings allow a preliminary distinction between codings of defense with questionable, moderate, or strong clinical significance, in the area of nonpsychotic psychopathology. PMID- 1891329 TI - Visual cues and attention demand in locomotor positioning. AB - The aim of this study was to determine what visual cues are used to assess the time-to-contact (Tc) with a stationary target during locomotor positioning. For this purpose, we performed an experiment with restricted central visual cues and analysed the attention demand involved in use of visual cues. 11 subjects were asked to walk towards a target surface and stop in front of it. Two target sizes were used: the tau strategy, consisting of assessing Tc from the relative expansion rate of the target during locomotion, was possible only with the larger one. The same task was also performed in a dual-task situation wherein reaction time to auditory stimuli was recorded. Analysis showed that braking was initiated earlier only in the dual-task situation involving the small target. The secondary task reaction time also increased considerably and actually even sooner when the positioning was done on the small target. These results suggest that a strategy other than tau may be used to assess Tc: with this strategy, the braking distance and walking speed are taken into account. Furthermore, different processing levels must have been involved in these two different methods, since the attention demand differed from one positioning task to the other. PMID- 1891330 TI - Cardiac reactions to two psychological stressors, acting in combination. AB - 56 student volunteers (mean age 21 yr.) participated in a study designed to assess how the Stroop procedure and delayed auditory feedback affect cardiac activity when they are used individually as well as when they are combined in the same task. In a preliminary study, listening to tape-recorded instructions on how to relax produced a significant decrease in cardiac activity. In the major study, when used individually, both the Stroop procedure and delayed auditory feedback produced significant increases in cardiac activity. The largest increase, however, occurred with systolic blood pressure and was induced by delayed auditory feedback. When the Stroop procedure was used in combination with delayed auditory feedback, systolic blood pressure again increased, but this effect was no greater than when delayed auditory feedback was used alone. This pattern of results implies that, when combined, the Stroop procedure and delayed auditory feedback have largely independent effects on cardiac activity and that, when tested under similar conditions, delayed auditory feedback has the larger effect. PMID- 1891331 TI - Accuracy of weightbearing estimation by stroke versus healthy subjects. AB - This study was performed to describe and compare the accuracy of weightbearing at three target levels (25, 50, and 75% of body weight) of 14 ambulatory stroke subjects and 14 matched healthy subjects. Weightbearing through a designated lower extremity (stroke subjects-paretic, healthy subjects-randomly selected) was measured with digital scales. No significant difference was found in magnitude of weightbearing (%) between the stroke and healthy groups. Although making significantly greater errors in weightbearing than healthy subjects, stroke subjects did not consistently weightbear under target. Subjects with stroke tested in earlier studies were neither asked to stand symmetrically nor examined to judge whether they were capable of accepting the required weight through the paretic lower extremity. Before assuming that weightbearing asymmetry is a problem in patients with stroke, clinicians should examine weightbearing behavior more specifically. PMID- 1891332 TI - Caffeine effects on behavioral thermoregulation. AB - Caffeine has a wide range of behaviorally active properties. Varying doses of caffeine solutions were administered (ip) prior to fixed-interval 2-min. schedules of microwave reinforcement in rats tested in a cold environment. Four Sprague-Dawley rats were conditioned to regulate their thermal environment with 5 sec. exposures of microwave reinforcement. Graphic descriptions showed that small doses of caffeine produced higher response rates for microwave heat than high doses of caffeine and saline controls, yet Friedman's nonparametric test showed no significant differences between dose levels. Synergism between thermogenic and discriminative properties of caffeine is proposed. PMID- 1891333 TI - An empirical note on tonic neck reflexes: control of the upper limb's proprioceptive sensation. AB - The effect of asymmetrical tonic reflexes on the upper limb in man was studied by analyzing errors in reproducing a targeted movement in right elbow extension following head rotation and vibration of the neck muscles. Overshoot of reproduction was observed only when the head was rotated to the left in contrast to no rotation or with rotation to the right. However, there was no influence on errors of reproduction after vibration of the neck muscles. These observations suggest that the proprioception in the rotated head controls the kinesthetic input by peripheral sensory receptors, namely, vestibular input plays a greater role in the accurate positioning of the upper limb, especially in inhibiting sensory input from the opposite side of the rotated head. PMID- 1891334 TI - Correlates of modified Stroop tasks, reading ability, and mental ability among college students. AB - 13 men and 13 women in college viewed 40 modified Stroop tasks consisting of line drawings with embedded words and nonwords. Scores on vocabulary, reading comprehension, and a mental abilities measure were correlated with percent errors on the modified Stroop tasks. Significant correlations (.34 to .70) were found. PMID- 1891335 TI - Event-related brain potentials and vigilance performance: dissociations abound, a review. AB - Event-related brain potentials (ERPs) have been suggested as a brain correlate of attention in sustained task performance. However, a review of the literature shows that changes in ERPs and performance measures over time often are dissociated. It is suggested that this may partly be caused by the simultaneous occurrence of several, separate processes in ERP trends over time. Further, it has been claimed that ERP recordings are more finely textured than behavioral measures such as hits, RT, sensitivity or response bias. Shortcomings of some studies are discussed and an approach is suggested which may more validly be employed in the search for relationships between time effects in ERP measures and measures of performance. PMID- 1891337 TI - Postextrasystolic potentiation does not distinguish ischaemic from stunned myocardium. AB - Myocardial function is impaired by ischaemia, and it remains depressed during reperfusion following short periods of ischaemia (stunned myocardium). We tested whether ischaemic and reperfusion dysfunction, in particular the time course of its recovery, can be distinguished by postextrasystolic potentiation (PESP). In eight open-chest dogs, posterior systolic wall thickening (sonomicrometry) was reduced by graded occlusion of the left circumflex coronary artery (LCX) from 17.4 +/- 6.8% (SD) during control conditions to 10.7 +/- 1.3% (mild ischaemic dysfunction), 7.2 +/- 2.3% (moderate ischaemic dysfunction), 3.6 +/- 1.4% (severe ischaemic dysfunction), and -4.4 +/- 3.6% (complete coronary occlusion). Extrasystoles with constant prematurity and a fully compensated postextrasystolic interval were induced after at least 4 min steady-state ischaemia. After each ischaemic period full recovery of posterior systolic wall thickening was assured. During 8 h of reperfusion following a 15-min LCX occlusion, extrasystoles were induced when posterior systolic wall thickening was comparable to one degree of the preceding ischaemic dysfunction. The increases in posterior systolic wall thickening induced by PESP were 10.5 +/- 5.8% during control conditions, during ischaemia they were 11.5 +/- 3.5% (mild dysfunction), 12.3 +/- 4.6% (moderate dysfunction), 12.6 +/- 4.1% (severe dysfunction) and 10.4 +/- 4.4% (complete coronary occlusion), and during reperfusion they were 12.8 +/- 8.2% (severe dysfunction), 13.0 +/- 9.7% (moderate dysfunction) and 10.7 +/- 2.2% (mild dysfunction).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1891336 TI - Alterations in renal inner medullary levels of amino nitrogen during acute water diuresis and hypovolaemic oliguria in rats. AB - Levels of total amino compounds (ninhydrinpositive substances, n.p.s.) have been measured in the inner medullas of rats during acute water diuresis and following the induction of hypovolaemic oliguria by the injection (i.p.) of 30% polyethylene glycol 20,000 (PEG) in 0.9% saline. Mean medullary fluid n.p.s. concentrations fell from 26.5 mmol to 15.2 mmol Gly equiv/l (-43%) within 2.5 h from the onset of diuresis, while the mean calculated tissue osmolality decreased from 738 mosmol/kg (control) to 369 mosmol/kg H2O. By 24 h n.p.s. and osmolality had returned to control levels. By 0.5 h after injection of PEG the mean concentration of n.p.s. had increased from 26.4 mmol to 32.7 mmol Gly equiv/l (+24%) and by 4 h had reached 60.4 mmol Gly equiv/l (+19%). During this time the calculated mean tissue fluid osmolality rose from 696 to 1037 mosmol/kg H2O. Levels of n.p.s. did not increase further for up to 12 h. It is proposed that losses of amino compounds may make a significant contribution to the overall decrease in medullary cellular osmotic potential accompanying reduced tissue fluid osmolality, and that increased levels of these solutes may provide short term osmoprotection during antidiuresis of rapid onset, in contrast to the more slowly accumulating methylamines and polyhydric alcohols. PMID- 1891338 TI - Modulation of calcium movements by nitroprusside in isolated vascular smooth muscle cells. AB - Using the patch-clamp technique, we have characterised the inward current from enzymatically dispersed rabbit pulmonary arterial cells, and investigated the effects of the vasodilator, nitroprusside (NP), on these and other membrane currents. With Cs(+)-filled pipettes, inward currents were recorded during brief depolarizing voltage steps in both physiological Ca2+ and 10 mM Ba2+. The threshold for current activation was positive to -40 mV and the current peaked at 0 mV for Ca2+ and +10 mV for Ba2+. During the first few minutes of recording, inward currents increased or "ran-up". This could not be attributed to blockade of outward current or the inclusion of adenosine triphosphate (ATP) in the patch pipette. Experiments revealed that all the inward current was carried through a single type of voltage-activated Ca2+ channel, namely the high-threshold, dihydropyridine-sensitive channel. It was unaffected by tetrodotoxin but was abolished at all potentials by low concentrations of Cd2+ (100 microM) or nifedipine (1-2 microM). NP (1 microM) suppressed peak inward Ba2+ current at +10 mV by approximately 45%. Higher concentrations (50 microM) did not produce further blockade of the current. This decrease was associated with increased inactivation of the current, and both effects required the presence of ATP in the patch pipette. In physiological Ca2+, using K(+)-filled pipettes, NP was found to induce spontaneous bursts of outward currents, which are probably activated by the release of Ca2+ from Ca(2+)-overloaded stores. These results are consistent with NP lowering cytosolic Ca2+, and hence causing vasodilation, by inhibiting Ca2+ influx through voltage-gated Ca2+ channels and by promoting Ca2+ uptake into the sarcoplasmic reticulum. PMID- 1891340 TI - Deutsche Physiologische Gesellschaft. Abstracts of the 70th meeting, (fall meeting) 8-10 September 1991, Freiburg and of the International Symposium: New trends in the analysis of vascular control mechanisms under physiological and pathophysiological conditions. 6-8 September 1991. PMID- 1891339 TI - Modification of liver cell volume by insulin and glucagon. AB - Cell volume plays a decisive role in the regulation of hepatic metabolism. The present study has been performed to test for an effect of insulin and glucagon on liver cell volume. To this end, the effect of these hormones has been studied in isolated perfused rat livers and isolated rat hepatocytes. Insulin leads to rapid stimulation of cellular K+ uptake and increase of cell volume, effects reversed by glucagon or cAMP. The insulin stimulated cellular K+ uptake is significantly decreased in the presence of either loop diuretics (furosemide or bumetanide) or amiloride and is completely inhibited in the presence of both, bumetanide and amiloride. The glucagon stimulated cellular K+ release in the presence of insulin is blunted by K+ channel blocker quinidine. The effects of insulin and glucagon on liver cell volume could participate in the regulation of hepatic metabolism by these hormones. PMID- 1891342 TI - [Experimental study of endoesophageal and intestinal expandable metallic stent placement]. AB - Gianturco expandable metallic stents were implanted into the esophagus and small intestine of 10 rabbits in order to evaluate the influence of wire stents on the gastrointestinal tract. The stents were constructed of 0.010 inch stainless steel wire. The relaxed diameter of the stents was 12-14 mm and the length was 10 mm. Except for one stent placed in the small intestine, the stents did not migrate and were covered with thickening mucosal epithelium. The mucosal inflammatory changes were slight, but severe intestinal adhesions were noted. The findings in the two groups were not significantly different at three and six weeks. Five rabbits died within three weeks of intestinal disorders caused by severe intestinal adhesions and/or perforations. The experimental data showed that implantation of metallic wire stents into the gastrointestinal tract resulted in severe damage to the esophagus and small intestine of rabbits. PMID- 1891343 TI - [MR imaging in paranasal and intracranial aspergillosis]. AB - The MR findings in three patients with paranasal and intracranial aspergillosis were analyzed. Two patients had sphenoid sinus aspergillosis with mucocele, and one had aspergillosis in the maxillary sinus and pachymeningitis in the posterior fossa. In all patients with aspergillosis of the paranasal sinuses, a markedly hypointense area was present within the lesion on T2-weighted images. In the patient with pachymeningitis, contrast-enhanced MR images clearly demonstrated the extent of the lesion. PMID- 1891341 TI - [MR imaging of the thymoma--differentiation of invasive thymoma from noninvasive thymoma]. AB - Magnetic resonance imaging (MRI) findings were reviewed in nine patients with histologically confirmed thymoma. The morphologic findings obtained by MRI were useful in distinguishing invasive from noninvasive thymoma. Invasive thymomas (2 cases) showed irregular contours and broad obliteration of the fatty plane between the mass and great vessels on T1-weighted coronary images. Perivascular infiltration shadow was considered to be characteristic of invasive thymoma. Noninvasive thymomas (7 cases) were round or oval in shape and showed slight obliteration of the fatty plane. In conclusion, MRI was helpful in differentiating invasive from noninvasive thymoma and defining the extent of thymoma. PMID- 1891344 TI - Pulmonary infection in patients with cyclosporine, azathioprine, and corticosteroids after cardiac transplantation. Clinical and radiographic assessment. PMID- 1891345 TI - [CT findings of muscular dystrophy: limb girdle type (LG), myotonic type (MYD) and Duchenne type (DMD)]. AB - CT scans of muscles in patients with LG, MYD and DMD were obtained at five different body levels: the neck, L3 vertebral body, pelvic girdle, thigh and lower leg. CT numbers, cross sectional areas (CSA) and %CSA of muscle or fat were evaluated in each muscle. The characteristic CT patterns for each type of muscular dystrophy were obtained. Compared with DMD, the gracilis and soleus were more severely damaged in LG and the biceps femoris remained relatively preserved among the hamstrings. In addition, the multifidus of the neck and sternocleidomastoid also were more severely damaged in MYD. This study suggests that CT scan will be useful in the differential diagnosis of these types of muscular dystrophy as well as in planning appropriate rehabilitation and detecting damaged muscles. PMID- 1891346 TI - [Basic and clinical studies of total body irradiation for bone marrow transplantation]. AB - Basic and clinical studies of total body irradiation (TBI) with respect to the dose distribution are described. TBI was performed with 10 MV X-rays at the Department of Radiology of Hyogo College of Medicine Hospital. Two opposed bilateral fields were used, the source-axis distance was 400 cm, and the dose rate was 10 cGy/min. At 55 cm from the rear concrete wall, the back-scattered radiation from the wall was 0.91% of the radiation dose. The beam flatness was +/ 2.9% within 130 cm of the diagonal by using a beam flattening filter improved. The surface dose was 93.5% of the peak dose by the acrylic bolus (1.5 cm thickness) placed on the source side 45 cm from the center of the body axis. We devised compensating filters using lead plates to improve dose distribution of the head, neck and thorax. The effectiveness of the compensating filters in producing a homogeneous dose distribution was checked by the thermoluminescent dosimeters (TLDs) in a Rando phantom. The average dose distribution to each site when the compensators used was 94% for the head, 104% for the neck, and 99% for the thorax when the scheduled dose was taken as 100%. TBI was performed 4 to 1 days before bone marrow transplantation, and 10 Gy was given in equal daily fractions of 2.5 Gy over 4 days. During TBI, the patients were placed in the supine position with the knees bent. The body surface dose was measured with pairs of TLDs at the head, neck, thorax, and pelvis in 32 patients. At the pelvis, the dose was measured simultaneously with an ionization chamber. The average doses were 91% for the head, 95% for the neck, 93% for the thorax, and 106% for the pelvis. PMID- 1891347 TI - [Results of radioiodine therapy in 47 patients with distant metastases of differentiated thyroid carcinoma]. AB - In the last ten years, 47 patients with distant metastases of differentiated thyroid carcinoma have been treated with 131I following total thyroidectomy. Post therapy whole body 131I scans revealed detectable uptake in the metastatic lesions in 23 (62%) of 37 patients with lung metastases, 10 (67%) of 15 patients with bone metastases five (71%) of seven patients with mediastinal metastases, and neither of two patients with brain metastases. The concentration of 131I in the metastases was significantly correlated with serum T3 and T4 concentrations, and inversely correlated with serum TSH concentrations. Most of the patients with a strong positive scan were euthyroid, suggesting that thyroid hormones produced by the tumor compensated for hypothyroidism following total thyroidectomy. There was no significant relationship between serum thyroglobulin concentration during T4 replacement therapy and 131I uptake or the efficacy of therapy. Twenty patients with lung (54%), five with bone (33%), two with mediastinal (29%), and none with brain metastases showed tumor regression after treatment. Significantly increased 131I uptake in lung metastases, better therapeutic results and better prognosis were demonstrated in young patients. In conclusion, age, 131I whole body scanning and serum thyroid hormone concentrations are considered to be useful in predicting the efficacy of 131I treatment for distant metastases, especially in the lung. PMID- 1891348 TI - [SPECT images after intravenous injection of 99mTc-DTPA in lung tumors- comparison with delayed 123I-IMP lung scintigraphy]. AB - The aim of this study was to assess the efficacy of SPECT imaging of the thorax with 99mTc-DTPA, which accumulates at sites of increased capillary permeability and expanded extracellular space, by comparing it with delayed 123I-IMP lung scintigraphy. We have previously reported that increased uptake on delayed 123I IMP lung scintigraphy was associated with atelectasis and inflammation. Thirteen patients with lung cancer (4 with atelectasis and 3 with pleurisy), one patient with malignant lymphoma complicated by pneumonia and pleurisy, and one patient with pneumonia were studied. 99mTc-DTPA scintigraphy was performed twice, 20-160 minutes and 2-4 hours after the intravenous administration of 370 MBq of 99mTc DTPA. 123I-IMP scintigraphy was performed 24 hours after the intravenous injection of 111 MBq of 123I-IMP. SPECT images were obtained with both types of scintigraphy. 99mTc-DTPA scintigraphy was compared with 123I-IMP scintigraphy for its ability to detect atelectasis and pneumonia. All patients showed increased accumulation corresponding to the lesions on both 123I-IMP and 99mTc-DTPA scintigraphy. 123I-IMP scintigraphy showed a defect corresponding to the tumor with increased accumulation around the tumor, whereas 99mTc-DTPA scintigraphy showed accumulation corresponding to the tumor. Ten of 11 tumors showed accumulation of an intensity equal to that of the soft tissue of the chest wall on 20-60 min 99mTc-DTPA images. The 2-4 hr images showed that 99mTc-DTPA leaked from the periphery of the tumor toward its center. All the patients with pleurisy showed increased accumulation in effusion on 2-4 hr 99mTc-DTPA scintigraphy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1891349 TI - [The new Greenfield vena cava filter, which can be inserted percutaneously]. AB - A clinical experience with the new Greenfield vena cava filter is described. It is made of titanium and is slightly larger than the original filter and can be inserted percutaneously through the 12 F sheath. The filter was inserted very easily and no significant complication was encountered. PMID- 1891350 TI - [MR cholangiography]. AB - A time-reversed gradient echo pulse sequence (PSIF; Siemens), one of the MR imaging methods based on steady-state free precession of excited spins, makes the bile duct quite bright relative to the surrounding tissue. Using this sequence under breath hold combined with a two or three-dimensional data set and maximum intensity projection method provided fair delineation of the dilated bile duct and the site of its obstruction or stricture. Though the clinical experience is limited, this technique is considered to be of value in the non-invasive evaluation of bile duct system in the patient of obstructive jaundice. PMID- 1891351 TI - [The clinical application of multi-voxel 1H-CSI (chemical shift imaging) in brain tumors]. AB - The 1H-Chemical shift imaging (CSI) method was developed and applied to reveal the metabolic changes in brain tumors. In the tumor, the decrease of NAA and the increase of lactate were observed by the CSI. These changes were more remarkable in the malignant tumors than in the benign tumors. The lactate was also observed in the tissue surrounding the tumors, which was supposed to be produced in the brain with hypoperfusion condition or to be leaked out from the tumor. The 1H-CSI has an advantage to demonstrate the pathophysiological changes in a wide area of the brain. PMID- 1891352 TI - Characterization by 1H NMR of glycosidic conformations in the tetramolecular complex formed by d(GGTTTTTGG). AB - We have conducted two dimensional NOESY studies on the molecule d(G2T5G2) to characterize the structure of the tetramolecular complex previously identified by calorimetric and spectroscopic studies (1). Analysis of the NOE and exchange cross peaks observed in the NOESY spectra establishes the formation of structured conformations at low temperature (5 degrees C). Significantly, within each strand of these structured conformations, the G1 and G8 residues adopt syn glycosidic torsion angles, while the G2 and G9 residues adopt anti glycosidic torsion angles. Consequently, any structure proposed for the tetramolecular complex of d(G2T5G2) must have alternating G(syn) and G(anti) glycosidic torsion angles within each strand. The implications of this observation for potential structures of the tetramolecular complex of d(G2T5G2) are discussed. PMID- 1891353 TI - Removal of psoralen monoadducts and crosslinks by human cell free extracts. AB - Human cell free extracts are capable of carrying out damage-induced DNA synthesis in response to DNA damage by UV, psoralen, and cisplatin. We show that this damage-induced DNA synthesis is associated with removal of psoralen adducts and therefore is 'repair synthesis' and not an aberrant DNA synthesis reaction potentiated by DNA deformed by adducts. By comparing the denaturable fraction of psoralen adducted DNA which becomes labeled in the repair reaction to that of terminally labeled DNA (without repair) we have found that all DNA synthesis induced by psoralen monoadducts is the consequence of removal of these adducts. By the same approach we have obtained preliminary evidence that this in vitro system is capable of removing psoralen crosslinks as well. PMID- 1891354 TI - Cloning and structural analysis of cDNA and the gene for mouse transcription factor UBF. AB - The gene and protein structure of the mouse UBF (mUBF), a transcription factor for mouse ribosomal RNA gene, have been determined by cDNA and genomic clones. The unique mUBF gene consists of 21 exons spanning over 13 kb. Two mRNAs coding for mUBF1 and mUBF2 having 765 a.a. and 728 a.a., respectively, are produced by an alternative splicing of exon 8. It specifies 37 amino acids constituting a part of the regions homologous to high mobility group proteins (HMG box 2). A human UBF (hUBF) cDNA obtained by polymerase chain reaction also indicates the presence of two kinds of mRNAs, the shorter form lacking the same region as mUBF2. Comparison of the cDNAs from hUBF and mUBF revealed an unusual conservation of nucleotide sequence in the 3'-terminal non-coding region. We examined the relative amounts of expression of mUBF1 and mUBF2. The eight tissues studied contained both molecular species, although mUBF2 was the predominant form of UBF. The mRNA of mUBF1 was expressed one half of the mUBF2 in quiescent mouse fibroblasts but reached the same amount in growing state. PMID- 1891356 TI - Analysis of inducers of the E.coli lac repressor system in mammalian cells and whole animals. AB - Although the inducible prokaryotic lac repressor system has been successfully adapted for control of gene expression in mammalian cells, little information is available on the pharmacokinetics of beta-galactoside inducers in mammalian cells for optimizing this system. These studies directly measure the cell uptake and clearance in cultured cells and animal tissue cells of lac inducers. In these cells, the beta-galactosides, isopropyl beta-D-thiogalactoside (IPTG) and methyl beta-D-thiogalactoside (MTG), are rapidly taken up, exceeding extracellular levels in less than 2 hours. Greater than 5% of this inducer is found in the nuclear fraction, slightly exceeding the cytoplasmic concentration. Although similar in uptake, IPTG is cleared from the cultured cells significantly faster than MTG. In the mouse, the half-life of both inducers in the blood ranges from 15-30 minutes. HPLC analysis of tissue extracts from inducer-injected mice indicates that the inducer is metabolically stable and functionally able to bind to lac repressor. These results should permit improvement in the adaptation of the lac repressor system to mammalian cells and aid in the development of an adaptable system for gene control in transgenic animals. PMID- 1891355 TI - Characterization of elongating T7 and SP6 RNA polymerases and their response to a roadblock generated by a site-specific DNA binding protein. AB - As a means of generating homogeneous populations of elongation complexes with the RNA polymerases encoded by phages T7 and SP6, transcription has been carried out in vitro on templates associated with the Gln-111 mutant of EcoRI endonuclease. The Gln-111 protein, as a result of a single amino acid substitution at position 111, lacks cleavage function yet shows higher than wild-type affinity for the EcoRI recognition sequence GAATTC. On a series of linear and circular templates associated with Gln-111 protein, blockage of the phage RNA polymerase elongation complex is observed. The 3' endpoint of the major blocked-length RNA species, just 3 bp upstream from the GAATTC, reveals an extremely close approach of polymerase's leading edge to essential contacts between Gln-111 protein and its binding site. In contrast to E. coli RNA polymerase, which is blocked stably and quantitatively by Gln-111 protein (Pavco, P.A. and Steege, D. A. (1990) J. Biol. Chem. 265, 9960-9969), the phage polymerases show substantial levels of readthrough transcription beyond the protein block. PMID- 1891357 TI - Software tools for analyzing pairwise alignments of long sequences. AB - Pairwise comparison of long stretches of genomic DNA sequence can identify regions conserved across species, which often indicate functional significance. However, the novel insights frequently must be windowed from a flood of information; for instance, running an alignment program on two 50-kilobase sequences might yield over a hundred pages of alignments. Direct inspection of such a volume of printed output is infeasible, or at best highly undesirable, and computer tools are needed to summarize the information, to assist in its analysis, and to report the findings. This paper describes two such software tools. One tool prepares publication-quality pictorial representations of alignments, while another facilitates interactive browsing of pairwise alignment data. Their effectiveness is illustrated by comparing the beta-like globin gene clusters between humans and rabbits. A second example compares the chloroplast genomes of tobacco and liverwort. PMID- 1891358 TI - SP6 RNA polymerase stutters when initiating from an AAA... sequence. AB - The 16S ribosomal RNA gene of Escherichia coli was placed under the transcriptional control of consensus and modified T7 promoters and a modified SP6 promoter. Both T7 and SP6 polymerases faithfully transcribed the coding sequence (beginning at the +1 position) of each construct, although SP6 polymerase was five-fold more effective than T7 polymerase in initiating with the AAAUUG... sequence. An appreciable fraction of the SP6 transcript molecules contained additional adenosines in the -1, -2, -3, -4, and -5 positions. The transcripts containing additional residues constituted approximately 40-50% of the total SP6 transcription products. Neither the nature nor extent of the additional residues was affected by replacing the pppA 5'-end by pA. Since the identity of the inserted residues does not correspond to the sequence of the template, these additional nucleosides must result from 'stuttering' of the SP6 enzyme at the -1 to +3 positions during initiation of transcription. PMID- 1891359 TI - Selection of sequences recognized by a DNA binding protein using a preparative southwestern blot. AB - We have tested the feasibility of using a preparative scale Southwestern blot to select DNA sequences specifically recognized by a DNA binding protein. We constructed a library of random 15-mer oligonucleotides and screened it using a preparative Southwestern blot with the transcriptional repressor, PRDI-BF1. Several sequences specifically recognized by PRDI-BF1 were isolated. All of these sequences are similar to PRDI, a regulatory element previously demonstrated to bind PRDI-BF1. PMID- 1891360 TI - Association of antisense oligonucleotides with lipoproteins prolongs the plasma half-life and modifies the tissue distribution. AB - In order to direct antisense oligonucleotides to specific tissues or cell types in vivo, we are exploring the possibility to utilize lipoproteins as transport vehicles. A 16-mer oligonucleotide (ODN) was derivatized at the 5' prime through a 32P phosphate spacer with cholesterol, yielding a 32P-labeled amphiphatic cholesteryl-oligonucleotide (cholODN). Incubation of cholODN with low-density lipoprotein (LDL) for 2 hr at 37 degrees C resulted in the formation of a cholODN LDL complex that migrates as a single peak on agarose gel electrophoresis. The cholODN was found to bind quantitatively to both high-density lipoproteins (HDL) and LDL, but not to albumin. Stable oligonucleotide-LDL particles with up to 50 molecules of cholODN per LDL particle could be obtained. In contrast, the control ODN did not show affinity for plasma lipoproteins. Upon injection into rats, cholODN became rapidly associated with plasma lipoproteins while control ODNs were recovered in the lipoprotein deficient serum fraction. The plasma half-life of cholODN (9-11 min) is considerably prolonged as compared with the control ODN (t1/2 less than 1 min). The cholODN-LDL was at least 5 min stable against degradation by rat plasma nucleases. It is concluded that derivatization of antisense oligonucleotides with cholesterol profoundly modifies their in vivo fate and opens possibilities for efficient and specific receptor-dependent targeting, mediated by lipoproteins coupled with specific recognition markers to various hepatic cell types. PMID- 1891361 TI - Altered response to growth rate changes in Kluyveromyces lactis versus Saccharomyces cerevisiae as demonstrated by heterologous expression of ribosomal protein 59 (CRY1) AB - We report the cloning, characterization and preliminary analysis of the regulation of the gene coding for ribosomal protein 59 (RP59) from the budding yeast Kluyveromyces lactis. The RP59 gene is present as a single copy, contains an intron within the amino terminal coding portion of the gene, and harbors conserved S. cerevisiae splicing signals. Sequence elements upstream of the transcriptional start site are homologous to UASRPG, known to regulate the transcription of numerous genes in S. cerevisiae via their interaction with the trans-activating factor RAP1. These elements are necessary for transcription of RP59 in both K.lactis and S.cerevisiae hosts. UASRPG in S.cerevisiae rp genes also modulate the transcription of rp RNA synthesis in response to a growth rate upshift. In K.lactis, the RP59 gene does not respond to growth rate upshift. Reciprocal expression of RP59 and CRY1 in heterologous hosts demonstrates that glucose upshift occurs in S.cerevisiae but not K.lactis. These results demonstrate that a factor or factors required for growth upshift are lacking in K.lactis, and provide further evidence that the UASRPG are sufficient signals for modulating this response. PMID- 1891362 TI - Medium reiteration frequency repetitive sequences in the human genome. AB - Fourteen novel medium reiteration frequency (MER) families were found, in the human genome, by using two different methods. Repetition frequencies per haploid human genome were estimated for each of these families as well as for six previously described MER DNA families. By these measurements, the families were found to contain variable numbers of elements, ranging from 200 to 10,000 copies per haploid human genome. PMID- 1891363 TI - Discrete regions of the avian beta-globin gene cluster have tissue-specific hypersensitivity to cleavage by sonication in nuclei. AB - We have analyzed the DNA released by sonication from avian nuclei, crosslinked with formaldehyde, by restriction mapping and equilibrium density gradient centrifugation. Our results indicate that regions flanking the adult beta-globin gene in adult reticulocytes have increased sensitivity to the mechanical shearing caused by sonication. These regions are near, and may overlap, the known nuclease hypersensitive regions that flank this gene. Like the hypersensitivity of these regions to nuclease digestion, the increased sensitivity to sonication is tissue specific and appears to be due chiefly to the absence of nucleosome structures in these regions. Analysis of crosslinked chromatin fractionated by density gradient sedimentation suggests that DNA sequences near the matrix attachment region/enhancer element located 3' to the adult beta-globin gene are associated with transcriptionally-engaged chromatin fractions from both adult reticulocytes and day 5 chick embryo primitive erythroid cells. Sonication appears to be a useful tool for the study of chromatin structure. PMID- 1891364 TI - An intron binding protein is required for transformation ability of p53. AB - Regulatory elements in intron sequences have been identified for several eukaryotic genes. The fourth intron of p53 is known to increase expression of p53 in a position dependent manner. We asked whether p53 intron 4 sequences interacted with DNA binding proteins to exact their effect. Three overlapping DNA fragments spanning the 5' end of p53 intron 4 were determined to specifically interact with protein in nuclear extracts from several cell lines by band shift analysis. Methylation interference experiments were used to identify purine residues involved in this protein-DNA interaction. Two G nucleotides were identified at intron 4 positions 33 and 44 and these were replaced by T and C, respectively. These two single base pair substitutions in the intron resulted in 1) lack of protein binding and 2) decreased expression of p53 as measured by a transformation assay. Thus the binding of protein to p53 intron 4 was shown to have functional significance. These experiments demonstrated a specific protein binding region in the 5' end of intron 4 critical for p53 expression and distinct from those elements already known to be involved in splicing. PMID- 1891365 TI - The Xenopus YB3 protein binds the B box element of the class III promoter. AB - We have isolated a Xenopus cDNA encoding the YB3 protein which binds specifically to the B box promoter element of class III genes. Northern analysis shows YB3 is expressed in a variety of adult tissues. Fractionation of oocyte S150 extracts demonstrates YB3 is present in phosphocellulose fraction IIIC, as well as in the fraction isolated by B box DNA affinity chromatography. Silver staining indicates that YB3, or a protein of the same mobility in SDS gels, is the most abundant component in either fraction. PMID- 1891367 TI - Nucleotide sequence of a new viroid species, citrus bent leaf viroid (CBLVd) isolated from grapefruit in Israel. PMID- 1891366 TI - Base mismatch-specific endonuclease activity in extracts from Saccharomyces cerevisiae. AB - An endonuclease activity (called MS-nicking) for all possible base mismatches has been detected in the extracts of yeast, Saccharomyces cerevisiae. DNAs with twelve possible base mismatches at one defined position are cleaved at different efficiencies. DNA fragments with A/G, G/A, T/G, G/T, G/G, or A/A mismatches are nicked with greater efficiencies than C/T, T/C, C/A, and C/C. DNA with an A/C or T/T mismatch is nicked with an intermediate efficiency. The MS-nicking is only on one particular DNA strand, and this strand disparity is not controlled by methylation, strand break, or nature of the mismatch. The nicks have been mapped at 2-3 places at second, third, and fourth phosphodiester bonds 5' to the mispaired base; from the time course study, the fourth phosphodiester bond probably is the primary incision site. This activity may be involved in mismatch repair during genetic recombination. PMID- 1891368 TI - A soybean embryo cDNA encodes a DNA binding protein with histone and HMG-protein like domains. PMID- 1891370 TI - Full length cDNA sequence encoding a nuclease-sensitive element DNA binding protein. PMID- 1891369 TI - A plant DNA binding protein shares highly conserved sequence motifs with HMG-box proteins. PMID- 1891371 TI - PCR driven DNA-DNA competitive hybridization: a new method for sensitive differential cloning. PMID- 1891372 TI - Single stranded rescue from phagemids in microtitre plates. PMID- 1891374 TI - Rapid non-radioactive TMACl hybridization protocol employing enzymatically labeled oligonucleotides. PMID- 1891373 TI - Improved telomere detection using a telomere repeat probe (TTAGGG)n generated by PCR. PMID- 1891375 TI - Direct sequencing by thermal asymmetric PCR. PMID- 1891376 TI - An STS in the human TNF locus located at 6p21.3. PMID- 1891377 TI - STS for minisatellite 33.1 (D9S49): direct typing by PCR. PMID- 1891379 TI - Dinucleotide repeat polymorphism in human GLUT2/liver facilitative glucose transporter gene on chromosome 3. PMID- 1891378 TI - Dinucleotide repeat polymorphism at the D11S527 locus. PMID- 1891380 TI - Pentanucleotide repeat length polymorphism at the human CD4 locus. PMID- 1891381 TI - Tetranucleotide repeat polymorphism at the human dihydrofolate reductase psi-2 pseudogene (DHFRP2). PMID- 1891382 TI - Tetranucleotide repeat polymorphism at the human prostatic acid phosphatase (ACPP) gene. PMID- 1891383 TI - Polymorphic dinucleotide repeat at the DXS3 locus. PMID- 1891384 TI - Tetranucleotide repeat polymorphism at the ACPP locus. PMID- 1891385 TI - Dinucleotide repeat polymorphism at the D17S513 locus. PMID- 1891386 TI - Dinucleotide repeat polymorphism at the D17S514 locus. PMID- 1891387 TI - PCR detection of an A/G polymorphism within exon 7 of the CYP1A1 gene. PMID- 1891388 TI - Hypervariable polymorphism in the APOC3 gene. PMID- 1891390 TI - Depression. Nursing implications of a clinical and social problem. AB - Depression is a phenomenon with concurrent personal, social, and clinical dimensions. Each person is affected by depression differently and expresses depressive symptomatology in a unique manner. Socially, the incidence of depressive illness in the general population is three times that of schizophrenia. The cost of depression in terms of lost days at work and treatment is estimated to be $29 billion in 1991. Diagnosing and treating depressive illnesses depend on the clinical manifestations of the illness and the assessment skills of the practitioner. Different treatment modalities such as psychotherapy, psychopharmacology, and electroconvulsive treatments can be effective singularly or in combination to assist the patient in regaining his or her functionality in daily life. PMID- 1891392 TI - Depression in adolescents. Context, manifestations, and clinical management. AB - The phenomenon of adolescent depression combines depressive symptoms with adolescent developmental variables and contextual factors, such as family patterns, ethnic background, socioeconomic status, gender, biologic factors, and individual experience with personal loss. These developmental and contextual factors lead to specific adolescent manifestations of depression, such as academic problems, sexual activity, substance abuse, conduct disorders, pain, eating disorders, and the potential for suicide. Assessment of the depressed adolescent includes specific questions concerning these possible manifestations and problem behaviors. Thorough assessment always includes questioning about the possibility and lethality of suicidal ideation. Modes of treatment include counseling, various forms of individual and group psychotherapy, environmental manipulation, and use of psychopharmacologic agents. Follow-up care is essential for the prevention or early treatment of future depressive episodes. The ultimate goal of care of the depressed adolescent is to prevent suicide and to minimize disruption of the adolescent developmental process. PMID- 1891391 TI - Childhood depression and suicide. AB - Recent years have witnessed accumulating evidence that the disorders subsumed under the heading of childhood depression are much more prevalent than used to be believed; that these conditions in prepubertal youngsters are more similar to those disorders occurring in adolescents and adults than was previously believed; that childhood depression can co-exist with many other childhood conditions; and that, although a rare occurrence, suicide is committed by older children. To quote a professional in the child mental health field: It is difficult to see how depression could not be involved in almost every form of psychopathology. The various theories of personality speculate on the existence of unhappy and depressing feelings and cognitions at the core of human development, with ineffective means of dealing with these concerns expressed by abnormalities. . . . Thus it becomes reasonable to argue that depression is everywhere in childhood and adulthood and hence we must be careful to specify under what conditions it is to be regarded as pathological. PMID- 1891393 TI - An integrated nursing model of depressive behavior in adults. Theory and implications for practice. AB - Accumulating evidence suggests that cognitive processes or stimuli associated with a stressor may influence the neurochemical state. In addition, it has been suggested that a person's coping responses may protect him or her from the biologic dysregulations implicated in depression. From a nursing care perspective, the proposed model suggests the following practice components. First, assessment not only should include the symptom profiles of each client but should address both physical and psychosocial stressors. Second, once identified, individualized care needs to incorporate a variety of interventions that focuses on the target components (i.e., cognitive interventions for negative thought patterns, interventions to build interpersonal skills, sleep hygiene principles, pharmacologic interventions, and so forth). Finally, one needs to address how having experienced episodes of depression may influence the client's self perception and ongoing quality of life. Nurses must begin to understand how the experience of having a depressive episode itself may serve as an ongoing stressor for the client. The factors that maintain depressive behavior and influence recurrence need to be the central focus of mental health nursing from a research and clinical perspective. It is this attention to integration and recurrence that will define nursing's unique contributions to this important area of mental health. PMID- 1891389 TI - New nucleotide sequence data on the EMBL File Server. PMID- 1891394 TI - Depression in the elderly. Characteristics and clinical management. AB - Major depression and clinically significant depressive symptoms occur commonly in the community-dwelling, medically ill, and institutionalized elderly. Both major depression and depressive symptoms need thorough evaluation and treatment because of the significant morbidity and mortality associated with these syndromes. Depression may be difficult to diagnose, especially in the medically ill elderly, because of the masking of depressive symptoms by somatic complaints or the presumption that symptoms are attributable to concurrent medical illness. Therefore, the clinician must be alert to the possibility of depression in the elderly patient. Although no specific diagnostic test is available, rating scales can be useful in screening for depression in the elderly patient. It is necessary to rule out medical illness or medications as contributing factors to depression. Psychotherapy and psychopharmacology, alone or in combination, are effective treatments for most elderly patients with depression. ECT is a safe and effective treatment for major depression in this population. Depression in the elderly is potentially a chronic and relapsing illness with significant associated medical and social morbidity. Because of their frequent contact with the elderly, nurses play a particularly important role in the diagnosis and treatment of depression. They need to recognize typical and atypical symptoms of depression and must be familiar with the potential side effects of antidepressant treatment. Close monitoring for these potential side effects can minimize disability. By working as a team with physicians, psychologists, and others, nurses have a necessary role in the care of the elderly depressed patient. PMID- 1891395 TI - Young women and depression. Origin, outcome, and nursing care. AB - Depression in young women occurs at a rate twice that of men. Physiologic, psychological, and social phenomena contribute to the development of this multifactorial disorder that interferes with the productivity of women at the height of their work and family careers. Neuroendocrine factors, both menstrually linked and independent of menstrual functioning, have been implicated in gender biased distribution of affective disorder. Equally salient for women are environmental and cognitive factors that contribute to loss of hope and a sense of helplessness in managing day-to-day responsibilities. Social discrimination and the social roles performed by women may expose them to more stresses or those that are not easily managed. Each of these factors may leave women more vulnerable to the onset of affective disorder. Despite this, there is much nurses can do in the prevention and treatment of depression using a biopsychosocial strategic approach. Psychoeducation, physiologic assessment and intervention, and a maintained caring interaction with the client can promote a return to normal mood and effective functioning for most women with affective illness. PMID- 1891396 TI - Depression in the general hospital. AB - Depression in the general hospital is a challenging arena for nursing. Diagnosing depression tends to be difficult because of the overlapping somatic presentations of depression and medical illness. In working with this patient population, a thorough physical examination and diagnostic evaluation need to be completed to rule out pre-existing medical diseases and medications that could be inducing the depressive symptoms. Usually, medically ill patients are diagnosed with adjustment disorder with depressed mood that responds well to a combination of supportive psychotherapy and antidepressant therapy. PMID- 1891397 TI - Adolescent suicide. Prevention, intervention, and postvention. AB - Suicide is a significant public problem, directly or indirectly affecting the lives of many Americans each year. There have been many different explanations for suicide over the centuries. Many who commit suicide suffer from medically identifiable depression. Clinicians must be alert for subtle self-destructive behaviors that reflect depression. Currently, in the United States, teenagers are increasingly at risk for suicide. Parents and teachers are in key positions to promote healthy living environments for this age group, recognizing suicidal behaviors and taking them seriously. This is the first step toward intervention. PMID- 1891399 TI - Practical psychopharmacologic considerations in depression. AB - Of the antidepressants on the US market, only alprazolam and trazodone have questionable antidepressant efficacy. Because all other antidepressants are equally effective in major depressive illness, drugs are used based on particular patient characteristics matched with individual antidepressant drug profiles. In general, antidepressant plasma concentration monitoring is only clinically useful with some of the TCAs. Nortriptyline, imipramine, and desipramine have demonstrated the highest correlation between clinical response and plasma concentration. MAO inhibitors are useful but require a reliable patient who can comply with dietary restrictions. Maprotiline and amoxapine are not first- or second-line antidepressants. Clomipramine and fluoxetine offer unique properties that make them first- or second-line antidepressants for particular patients. There are significant drug interactions with antidepressants that should be avoided. PMID- 1891398 TI - Therapeutic group work with depressed elderly. AB - This article presents several approaches to therapeutic group work with the elderly, drawing from experience in designing and implementing several group interventions for frail nursing home residents. What is important to recognize is that the common preconception that the elderly, in general, and the frail, in particular, cannot participate in therapy and groups is a misconception at least, if not a prejudice. PMID- 1891400 TI - The conspiracy of culture. Women's issues in body size. AB - This article challenges nurses to rethink cultural values and ideals regarding beauty and body weight, respond appropriately to persons suffering from any of the eating disorders, and work together to change self-deprecation into a celebration of womanhood. PMID- 1891401 TI - Eating disorders. Highlights of nursing assessment and therapeutics. AB - Nurses providing care for individuals with eating disorders should identify and test the effectiveness of various milieu factors and nursing therapeutics employed in the treatment of these often-debilitating disorders. Nurses offer presence, role modeling, surveillance, and emotional and physiologic support while guiding reluctant patients to explore and experiment with new behaviors. Nurses provide flexibility, empathy, and rational limit setting in response to the unique and shifting needs of each patient. This interpersonal dynamic is often extremely different from that experienced in the patient's family of origin and, thus, contributes to the essential "interpersonal conditions" that are necessary for the patient to engage meaningfully in treatment. The prevalence of eating disorders suggests that nurses are likely to encounter people with eating disorders in many settings. Nurses should be skilled at spotting disordered eating among an array of clinical presentations (e.g., amenorrhea, disturbed family relationships, athletic injuries) because people engaged in disordered eating are hesitant to volunteer such information. In addition to the shame associated with disordered eating is the stigma associated with psychiatric treatment. Seeking help from a nurse may be perceived as less stigmatizing than seeking care from a psychiatrist. Thus, nurses may serve as important points of entry for the hesitant patient. The initial contact is so essential in setting the stage for the continuation and denouement of therapy. Finally, nurses and patients with disordered eating share at least one commonality. Both groups are predominantly women. The prevailing culture has been implicated repeatedly as a major factor in contributing to the prevalence of disordered eating. Nurses experience the influences of paternalism in their professional practice and confront daily the pressures of socially constructed feminine ideals. These gender-sensitive ways of knowing, which nurses bring to the treatment relationship, should be further analyzed as substantive dimensions with treatment and preventive potential. PMID- 1891402 TI - Compulsive overeating. AB - Compulsive overeating is a behavior used in an attempt to numb or nurture feelings that are threatening to the person. Emotional states are soothed by use of food. Treatment is designed to respond to internal, biologic causes of hunger and satiety while simultaneously allowing feelings to surface and be dealt with. Work on the inner child enables the person to identify and deal with unmet needs and correct distortions from childhood. The secondary gain realized from the extra weight is examined, and direct means of dealing with these needs explored. The focus of recovery is on learning to nurture the self, physically and emotionally. PMID- 1891403 TI - Eating disorders as a special problem for persons with insulin-dependent diabetes mellitus. AB - Diabetes and eating disorders can be a deadly combination. Patients may omit or reduce their insulin dosages, which will induce glycosuria. Counseling and behavior modification are essential to prevent the development of complications such as DKA, frequent hypoglycemia, and the early onset of chronic complications. Diabetes education and insulin regulation must be combined with an interdisciplinary team approach to correct maladaptive coping mechanisms. PMID- 1891404 TI - Eating disorders as addictive behavior. Integrating 12-step programs into treatment planning. AB - To be effective in treating eating-disordered individuals, we must be open to working with an electric model of treatment. Often health care providers have difficulty with the addiction model of treatment, even though many eating disordered patients will attest to the assistance and support they receive from these programs. It will be useful for both health care professionals and 12-step programs to avoid taking competitive positions. It is far more useful for professionals to have a working knowledge of how these programs work and how they can be of use to the individuals with eating disorders. Knowledge of local resources will also be of great value. Given the assistance that the clients tell us they receive at these programs, it makes more sense to understand and use these programs more, not less. There is evidence that eating disorder behaviors are addictive behavior, both from a psychological and physiologic perspective. Use of a 12-step program will assist with the practical details of helping individuals to stop employing self-destructive behaviors as well as provide support and decrease feelings of isolation and depression. It is important to integrate the 12-step program components into an overall treatment program to make the best use of both programs and decrease the competition usually inherent in both programs. PMID- 1891406 TI - Unlocking sexual issues. Counseling strategies for nurses. AB - Providing truly holistic care means that nurses must recognize that their clients are sexual beings and that they often suffer from sexual concerns and problems related to their past history and their current medical problems. In addition to helping clients move toward physical wellness, nurses should intervene with intrapersonal and interpersonal problems affecting client's sexual feelings and behaviors. PMID- 1891405 TI - Body-image therapy. AB - Body image is a complex interplay of factors resulting in a sense of the body perceived by that individual. In eating-disorder clients, there is a distortion between their perceived image of their body and its actuality. This is combined with a sense of dissatisfaction and alienation of mind and body. Cognitive, right brain, and kinesthetic strategies are described that seek to decrease distortion and dissatisfaction and facilitates individuation-separation and a reintegration of the self. These strategies are both therapeutic and evaluative. Cultural expectations of women have had a profound impact on the proliferation of eating disorders, and they account for the fact that body distortion is found in both normal and eating-disordered women. PMID- 1891407 TI - Healing the wounded, neglected inner child of the past. AB - Childhood experiences of the past can have a destructive effect on the present. The inner child in each person is the core of the personality that has been molded by the directions on how to act to be loved that the person receives in childhood. Painful experiences and lack of nurturing in dysfunctional families wound the inner child and contaminate adult experiences. Many persons with eating disorders have a wounded or neglected inner child that affects their adult lives. Characteristically, they demonstrate problems with trust, intimacy, addictive and compulsive behaviors, and codependence among others. Healing the inner child by grieving neglected childhood developmental needs is a long process, but one that improves the quality of one's life. Nurses, depending on their educational background and clinical skills, can help clients move toward understanding and healing the wounded, neglected inner child of the past. PMID- 1891408 TI - Effective limit setting. How to avoid being manipulated. AB - Nurses who remember that control of behavior belongs to the client, not the staff, will be less likely to become enmeshed in power struggles. Gartside states, "The destruction of self is the ultimate rebellion--yet rebellion can be a healthy phase of development. To help individuals back towards healthy rebellion, we must listen to our clients." Listening and limit setting are nurses' most effective approaches for dealing with manipulation. PMID- 1891409 TI - Codependency and the eating-disorder client. AB - The treatment of eating-disordered individuals with codependency is difficult. This article reviews the causes of eating disorders and codependency and cites similarities between these disorders. The recovery process and treatment needs of this population are explored. Psychotherapy, which is the treatment of choice, is reviewed in detail. PMID- 1891410 TI - Body contouring and weight loss surgery for obesity. PMID- 1891411 TI - The primary prevention role of the nurse in eating disorders. AB - Mental health depends on establishing an equilibrium between bodily needs, drives, and demands from the environment. A balance must be maintained between the basic human urges, self-centered wishes, and the demands of both conscience and society at every stage of human development. Eating and feeding behaviors are bound up with family dynamics and are often a barometer of the family's emotional climate and parent-child interactions. A positive feeding relationship is a concrete measure parents can be taught to provide for the child's healthy psychosocial development. Although the development of eating disorders is complex and caused by a multiplicity of factors, community-wide education by nurses about nutrition and feeding at successive developmental levels from infancy to old age can decrease the incidence of eating disorders in the community. Evaluation of prevention programs is essential to guarantee the refinement of preventive efforts over time. PMID- 1891412 TI - Central venous catheter complications. PMID- 1891413 TI - Two faces have I. PMID- 1891414 TI - Self-transcendence and emotional well-being in women with advanced breast cancer. AB - Self-transcendence has been associated, in previous studies, with stressful life events and emotional well-being. This study examined the relationships among self transcendence, emotional well-being, and illness-related distress in women with advanced breast cancer. The study employed a cross-sectional correlational design in a convenience sample (n = 107) of women with Stage IIIb and Stage IV breast cancer. Subjects completed a questionnaire that included Reed's Self Transcendence Scale; Bradburn's Affect Balance Scale (ABS); a Cognitive Well Being (CWB) Scale based on work by Campbell, Converse, and Rogers; McCorkle and Young's Symptom Distress Scale (SDS); and the Karnofsky Performance Scale (KPS). Data were analyzed using factor analytic structural equations modeling. Self transcendence decreased illness distress (assessed by the SDS and the KPS) through the mediating effect of emotional well-being (assessed by the ABS and the CWB Scale). Self-transcendence directly affected emotional well-being (beta = 0.69), and emotional well-being had a strong negative effect on illness distress (beta = -0.84). A direct path from self-transcendence to illness distress (beta = -0.31) became nonsignificant (beta = -0.08) when controlling for emotional well being. Further research using longitudinal data will seek to validate these relationships and to explain how nurses can promote self-transcendence in women with advanced breast cancer, as well as in others with life-threatening illnesses. PMID- 1891415 TI - Nutritional status, pressure sores, and mortality in elderly patients with cancer. AB - This prospective study aimed to determine differences in nutritional status, incidence of pressure sores, and incidence of mortality between two groups, one composed of 33 elderly, institutionalized patients with cancer and the other a matched group of 33 patients without cancer. Subjects with cancer were paired with subjects without cancer based on age (mean = 78), sex, and pressure sore risk. Skin breakdown, dietary intake, and blood and serum indices of nutritional status were studied for 12 weeks. Of the subjects with cancer, 85% developed pressure sores, compared to 70% of the subjects without cancer. Hemoglobin (Hgb) (female), serum total protein, total lymphocyte count, serum albumin, serum total iron binding capacity, and serum transferrin were significantly lower in subjects with cancer with pressure sores than in subjects without cancer with pressure sores. Total lymphocyte count and serum total protein were significantly lower in subjects with cancer with pressure sores than in subjects with cancer without pressure sores. Kwashiorkor was found in 70% of the subjects with cancer, compared to 21% of the subjects without cancer. During the study, 39% of the subjects with cancer and 15% of the subjects without cancer died. All 13 of the subjects with cancer who died had kwashiorkor and pressure sores and had died an average of three weeks after developing pressure sores. These results implicate that elderly patients with cancer who have protein deficiencies should be considered to be at risk of pressure sore development. Frequent repositioning and mattress overlays that reduce pressure and increase comfort may delay development of pressure sores.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1891416 TI - HIV-related non-Hodgkin's lymphoma. AB - Non-Hodgkin's lymphoma (NHL) is the second most prevalent malignancy in patients infected with HIV. Approximately 30,000 new cases of NHL are diagnosed annually, and individuals with immunodeficiencies have a greater likelihood than the general population of developing NHL. Moreover, individuals who are seropositive for HIV have a fourfold greater risk of acquiring NHL. Most of these individuals will manifest NHL as a high-grade B-cell lymphoma with extranodal presentation. Response to standard chemotherapy and/or irradiation occurs frequently. However, because of opportunistic infections, overall survival is approximately five months. The expert nurse's role in assessment and management of symptoms associated with infection and side effects of therapy is critical. PMID- 1891417 TI - Use and perceived efficacy of self-care activities in patients receiving chemotherapy. AB - Information about chemotherapy side effects and the efficacy of self-care activities used to deal with these side effects is needed to direct nursing interventions for patients receiving chemotherapy. Using the self-care diary (SCD) developed for this study, a sample of 49 adult patients with cancer recorded their side effects, rated the severity of each side effect, and reported on the use and efficacy of self-care activities two days after treatment. Data were collected again five days after treatment to examine the test-retest reliability of the side effect severity component of the SCD. The most common side effect, experienced by 81% of the subjects, was fatigue. Other side effects reported by more than one-third of the subjects were sleeping difficulty, nausea, decreased appetite, and changes in taste or smell. The most frequently reported side effects received mean severity scores indicative of moderate severity. The most commonly used self-care activities were rated as providing some relief to moderate relief of individual side effects. None of the reported self-care activities received mean efficacy ratings that indicated complete side effect relief. PMID- 1891418 TI - Quality of life of patients with sarcoma postchemotherapy. AB - This study was designed to describe the effects of a 96-hour doxorubicin hydrochloride/dacarbazine chemotherapy protocol for soft-tissue sarcoma on patients' functioning, life-style, and quality of life (QOL). Patients from the surgical oncology clinic of a large, midwestern university completed the Quality of Life Index--Cancer Version (QLI) and Functional Living Index: Cancer (FLIC). Additional information obtained regarded response to chemotherapy and demographic data. Patients were most satisfied with faith in God, family health, health care, long life, and their spouse. Patients were least satisfied with sex life, stress or worries, unemployment, financial independence, and government influence. QOL in the family domain was found to be significantly higher than QOL in the health, functioning, and socioeconomic domains (p less than 0.05). Functional living assessment indicated that patients were confident in their prescribed course of treatment, optimistic about the future, generally felt well, and felt that their QOL had improved since treatment. Aspects of chemotherapy that most interfered with patients' lives were the length of treatment and the financial burden. The patients reported a high confidence level in the medical and nursing care that they received. PMID- 1891419 TI - Cutaneous T-cell lymphoma. AB - Cutaneous T-cell lymphoma (CTCL) represents a spectrum of the non-Hodgkin's lymphomas, including mycosis fungoides (MFs) and Sezary syndrome. Although an uncommon malignancy, the number of new cases per year in the United States is increasing at a constant rate. This paper provides an overview of CTCL, including pathophysiology, information on the various treatment modalities, and practical clinical approaches needed by oncology nurses to assist individuals experiencing treatment-related toxicities. Psychosocial issues, an aspect of disease in which oncology nurses can provide support and understanding, also are addressed. PMID- 1891420 TI - Ageism in cancer care of the elderly. AB - This paper explores the existence and effects of ageism on cancer care of the elderly. Cancer-related care for the elderly patient has not been given appropriate attention. Many of our present attitudes are based on how history has treated the elderly. Screening programs often neglect individuals over 65 despite the increased prevalence of cancers in this age group. Little research evaluating age-related toxicities has been conducted, and no age-related guidelines for chemotherapy administration are available. Of the three modalities (chemotherapy, radiation therapy, and surgery), surgery has made the greatest change in practice based on an understanding of the aging process. Increasing prevalence of cancer in patients over 65, coupled with a projected increase in the numbers of uninsured, will change the demographics and the economics of cancer care dramatically. Early detection and prevention programs targeted toward tomorrow's elderly, who are today in their middle years, have the potential to significantly decrease both morbidity and mortality. PMID- 1891421 TI - Skin cancer and melanoma awareness campaign. AB - Nonmelanoma skin cancer is the most common form of cancer in the United States. The incidence of melanoma is increasing more rapidly than any other form of cancer (with the exception of lung cancer in women). Public education programs have the potential to prevent future skin cancers and promote early detection of skin cancer and melanoma. This article describes a statewide awareness campaign and outlines important nursing activities and educational resources. Among results of a pre- and postevaluation poll are an increase in the number of respondents correctly identifying melanoma as the most serious type of skin cancer and an increase in the number of respondents who stated that sunburn in children was very serious. PMID- 1891422 TI - A nursing flow sheet for documentation of ambulatory oncology. PMID- 1891423 TI - Pain control with sublingual or buccal morphine. PMID- 1891424 TI - Is VP-16 compatible with D5W solutions? PMID- 1891425 TI - Exit-site care and the Oncology Nursing Society Access Device Guidelines. PMID- 1891426 TI - Narcotic oral equivalents. PMID- 1891427 TI - Pain associated with peripheral infusion of carmustine. PMID- 1891428 TI - Continuing a tradition of excellence. Second Annual Fall Institute, Oncology Nursing Society. Atlanta, Georgia, October 18-20, 1991. PMID- 1891429 TI - Is your overhead 70%? PMID- 1891430 TI - HIV screening of travelers to eastern Europe. PMID- 1891431 TI - Alzheimer's disease. Recognizing and treating a frustrating condition. AB - Alzheimer's disease is a costly illness affecting large numbers of older Americans, and its prevalence is increasing. The major symptom of the condition is progressive forgetfulness. The course is variable, depending on which areas of the brain are affected earliest and most severely. In diagnosing Alzheimer's disease, it is important to rule out other types of dementia that may be treatable, as well as systemic and affective disorders and other brain diseases. The Mini-Mental State Examination and the category fluency test are often diagnostically useful. There is no evidence that any of the therapeutic agents studied so far are of much value, but pharmacologic agents can be useful in treating the depression, psychoses, and anxiety that may accompany cognitive decline. Patients cared for at home need a structured, orderly environment that has been modified for their safety. PMID- 1891432 TI - Managing the care of patients with dementia. How to maximize level of functioning and minimize behavior problems. AB - Effective treatment of patients with dementia involves supporting and educating the primary caregiver, uncovering and correcting the underlying cause of any decompensation that may occur, and deciding when drug therapy is appropriate. Caregivers must be taught how to cope with the patient's denial and how to modify the patient's environment so that it is safe and easy to understand. Pharmacologic therapy for depression accompanying dementia can improve a patient's quality of life and independence considerably; drugs may also be of help in dealing with patients who resist care. Psychotic symptoms usually do not require pharmacologic treatment, and hypnotics should, if possible, be avoided as a solution to sleep problems. PMID- 1891433 TI - Cocaine-induced myocardial infarction. A growing threat to men in their 30s. AB - A clear association has been established between cocaine use and acute myocardial infarction. Because of the continuing rise in cocaine use in the United States, many more young patients have or will have this disorder. Such patients are usually managed conservatively with calcium channel blockade and have an excellent in-hospital prognosis. If chest pain recurs or stress testing reveals evidence of ischemia, cardiac catheterization should be done. If cocaine use is discontinued, the long-term prognosis of a typical patient with cocaine-induced acute myocardial infarction is excellent in the absence of other chronic illnesses. PMID- 1891434 TI - Assessing an adult patient's suicide risk. What primary care physicians need to know. AB - There is no pathognomonic sign or symptom that predicts suicide. However, suicide threats, hopelessness, and other risk factors may signal a patient's intent for self-harm. Through careful history taking and examination, the physician can assess the patient's risk profile for suicide and construct an appropriate treatment plan, which may include hospitalization, drug therapy, and/or referral to a psychiatrist. PMID- 1891435 TI - Jaundice and cholestasis. Some common and uncommon causes. AB - Jaundiced patients may not always be as sick as they look, and cholestatic patients may be quite ill but not yet jaundiced. There is variability in presentation of cholestasis, and jaundice may be intrahepatic or extrahepatic and acute or chronic. Even though the diagnosis of jaundice can be elusive, an unnecessarily exhaustive search for a cause should be avoided, because some tests are not without dangers. Dr Gordon describes many possible causes, some of which are rare but are still worth consideration. PMID- 1891436 TI - Sassafras tea and diaphoresis. AB - A patient whose main symptom is sweating can present a diagnostic challenge. Dr Haines describes a case in which diaphoresis was caused not by a conventional medication or illness but rather by a life-style change in which the patient began consuming sassafras tea. PMID- 1891437 TI - Applications of autometallography to heavy metal toxicology. AB - Application of autometallography (AMG) to histological material from humans and animals exposed to gold, silver and mercury has made it possible to localize these heavy metals at light and electron microscopic levels. Because of high sensitivity of the technique, traces of the three metals have been demonstrated in tissues and cells that had previously not been suspected of containing metals. A chelatable pool of zinc in the synaptic vesicles of the zinc-positive neurones can be demonstrated by AMG in the brain. The well defined staining pattern can be used to estimate volumes of cortical subdivisions. Volumetric studies based on autometallographic differentiation of cortical regions have provided valuable information about the effects of different toxicants. AMG can be combined with new quantitative methods, such as electron energy loss spectroscopy (EELS), electron probe X-ray microanalysis (EPMA) and laser microprobe mass analysis (LAMMA), to enhance detection of AMG metal catalysts with these techniques. PMID- 1891438 TI - Effects of lipophilic complex formation on the uptake and distribution of some metals in fish. AB - Dithiocarbamates, xanthates, dialkyldithiophosphates and pyridinethiones are groups of compounds which can form lipophilic complexes with heavy metals. These compounds are widely used in industry and in agriculture and forestry and may pollute the aquatic environment. We have exposed fish (brown trouts) to substances belonging to these groups of compounds together with heavy metals (Cd2+, Ni2+, Hg2+, CH3-Hg+ or Pb2+) and then examined the uptake of the metals in the tissues of the fishes. Some of the examined complexing substances were found to cause highly increased tissue levels of the metals in the trouts. However, the enhancing effects varied for different complexing substances and for different metals. A facilitated penetration of the lipophilic complexes over the gill membranes and cellular membranes in other tissues may underlie the increments in the tissue levels of the metals. The lipophilicity and the stability of the complexes may be of importance for the effects of the substances on the disposition of the metals. Studies by other authors, in fishes as well as in other aquatic organisms, have also shown enhanced metal accumulation by compounds forming lipophilic complexes. It is considered that this type of interaction may have important implications for the behaviour of metals in aquatic ecosystems. PMID- 1891439 TI - Mitogenicity and metallothionein induction: two separate effects of zinc ions on human mononuclear blood cells. AB - The mitogenic effect of elevated concentrations of zinc ions on human lymphocytes was found to be inhibited by the glucocorticoid hormone dexamethasone. The effect decreased progressively from complete block to partial inhibition when the culture period before the addition of dexamethasone was prolonged. In contrast, dexamethasone did not inhibit an induced formation of metallothionein in mononuclear cells. Furthermore, dexamethasone itself was found to induce small amounts of metallothionein. Apparently, the mitogenic effect and the induction of metallothionein by zinc ions in mononuclear cells occur by mutually independent mechanisms. PMID- 1891440 TI - Effect of trimethyltin on amino acid concentrations in different regions of the mouse brain. AB - Trimethyltin (TMT) is a neurotoxic compound known to cause marked alterations in brain chemistry. We have previously demonstrated that a single oral dose of TMT produced a dose-dependent decrease in muscarinic cholinergic receptors in mouse brain and significantly elevated glutamine in several regions of the rat brain. This study was designed to determine if TMT produced dose- and time-related alterations in amino acid concentrations in the adult male C57BL/6N mouse brain and in peripheral organs and plasma. In the dose-response study, TMT was administered orally as a single dose of 0, 0.5, 1.0, 3.0 or 5.0 mg/kg and animals were sacrificed 24 hr after treatment. In the time-course study, mice were dosed with TMT at 3.0 mg/kg and sacrificed 4, 12, 24, 48 or 96 hr after dosing. Amino acid concentrations were quantified by HPLC/EC following precolumn derivatization with o-phthalaldehyde-tert-butylthiol. TMT produced dose-dependent increases in aspartate, glutamine and glycine in the caudate nucleus (CN), frontal cortex (FC) and hippocampus (HIP) at 3.0 and 5.0 mg/kg. TMT at 3.0 mg/kg produced significant increases of aspartate in FC and HIP after 48 hr. Glutamine concentrations were significantly increased at 24 and 48 hr in HIP and at 48 hr in CN. Glycine and GABA concentrations were significantly increased at 48 and 96 hr respectively in the HIP. Glutamine was increased in plasma at 4 and 12 hr and in liver at 24 hr. Hyperammonemia occurred in plasma after 8 hr and continued through 24 hr and was accompanied by an increase in serum urea nitrogen.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1891441 TI - Distribution of mercury in rabbits subchronically exposed to low levels of radiolabeled methyl mercury. AB - The metabolism of methyl mercury (MeHg) has been studied in rabbits administered 203Hg-labeled methyl mercuric chloride, 0.125 mumol/kg body weight, twice a week for 9 weeks, by intravenous injection. Twelve weeks after cessation of treatment, about 54% of the administered dose had been excreted in faeces and 5% in urine. After one week, the highest concentration of 203Hg was found in fur (8.6 nmol Hg/g). Substantially lower concentrations were found in kidney (2.5 nmol/g), liver (0.9 nmol/g), brain (0.4 nmol/g), muscle (0.3 nmol/g) and blood (0.1 nmol/g). The rate of elimination of 203Hg from brain, muscle and blood was faster (t1/2 about 12 days) than that from kidney and liver (t1/2 about 28 days). The relative amount of inorganic Hg in kidney and liver increased with time after cessation of treatment. The highest fractions were 85 and 70%, respectively. In brain, no significant demethylation of MeHg could be detected. PMID- 1891442 TI - Possible role of glutathione in chromium(VI) metabolism and toxicity in rats. AB - The effect of Cr(VI) on liver, kidney, and lung glutathione (GSH) levels and the effect of GSH depletion on Cr(VI)-induced nephrotoxicity were studied in male Sprague-Dawley rats (150-200 g). GSH levels, measured as nonprotein sulfhydryls, were determined between 0.5 and 26 hr after intraperitoneal injection of the maximum non-toxic dose of sodium dichromate (10 mg/kg). While Cr(VI) at this dose did not significantly change hepatic, renal, or pulmonary GSH levels, there appeared to be an initial decrease of hepatic GSH followed by an increase to approximately 120% of control between 5 and 12.5 hr after Cr(VI) treatment. The increase in hepatic GSH levels was significant 5 hr after treatment with 20 mg/kg sodium dichromate, was manifested as an increase in both non-protein sulfhydryls and total glutathione, and was prevented by L-buthionine sulfoximine (BSO) pretreatment. In rats pretreated with 4.0 mmol/kg BSO to deplete GSH, subsequent treatment with Cr(VI) further reduced hepatic GSH levels 2 hr after Cr(VI) treatment and inhibited weight gain in the first 24 hr after treatment. Intraperitoneal injection of Cr(VI) did not inhibit hepatic glutathione reductase activity, even at toxic doses. Depletion of renal GSH to approximately 25% of control with BSO potentiated the acute nephrotoxicity of 30 mg/kg sodium dichromate as measured by serum urea nitrogen levels and relative kidney weight. However, GSH depletion with BSO did not appear to affect the incidence of glucosuria, haematuria, or lysozymuria over a range of Cr(VI) doses, nor did it affect renal uptake of Cr. Taken together, these data show that GSH protects against the acute nephrotoxicity of Cr(VI), although it is not clear whether GSH is directly involved in the intracellular metabolism of Cr(VI) at non-toxic doses. PMID- 1891444 TI - Cadmium and zinc kinetics in fish: studies on water-borne 109Cd and 65Zn turnover and intracellular distribution in minnows, Phoxinus phoxinus. AB - This study investigates the short- and long-term turnover of zinc and cadmium in fish. Juvenile minnows, Phoxinus phoxinus, were exposed to water-borne 109Cd and 65Zn for 24 hr. Tracer uptake, redistribution, elimination, and intracellular tracer distribution were studied for 60 days in tracer-free water. The influx of 65Zn from the water to the internal organs was more rapid than the influx of 109Cd, and the 65Zn turnover in the liver and kidney was considerably faster than the turnover of 109Cd. Moreover, in the gills and kidney, intracellular 65Zn was more mobile between intracellular compartments than 109Cd. The liver and kidney accumulated the major part of the 109Cd originating from the gills, whereas the head and skin, and muscle and bone-fractions retained the majority of the 65Zn. This indicates that the metals have different pathways in the fish body, after entering the body from the water. The cadmium levels in the gills, liver and kidney increased drastically because of the cadmium exposure, but the zinc levels in the organs were not markedly affected by a fifteen-fold increase in external zinc concentration, indicating a homeostatic control of zinc in the minnow. PMID- 1891443 TI - Kinetics of lead in bone and blood after end of occupational exposure. AB - In 14 retired lead workers, followed for over 18 years after end of exposure, repeated analyses of lead levels in finger bone by an in vivo X-ray fluorescence method revealed a decrease of lead concentration. The data were analysed using an exponential retention model. For the whole group the biological half-time was 16 (asymptotic 95% confidence interval, CI 12,23) years. The median of the estimated bone lead levels at the end of exposure was 85 micrograms.g-1 above the "background" (3 micrograms.g-1). A simultaneous follow-up of blood lead levels displayed a decrease, which could be described by a tri-exponential retention model with group half-times of 34 (CI 29,41) days, 1.2 (CI 0.9,1.8) years, and 13 (CI 10,18) years, respectively. The median of the estimated blood lead levels at the end of exposure for the three components were 0.49, 0.61, and 1.1 mumol.l-1 above the "background" (0.38-0.56 mumol.l-1), respectively. The well-documented decrease of lead exposure in the general population over the years, urged the use of a decreasing "background" of blood lead during the time of the study. The slowest of the three components represented the skeleton (probably mainly cortical bone), as did mainly probably also the intermediate one (trabecular bone). The data show the rather slow turnover of lead in the skeleton, the usefulnes of in vivo skeletal lead measurements as a long-term exposure index, and the importance of bone as a source of "endogenous" lead exposure. PMID- 1891445 TI - The importance of metallothionein for the accumulation of copper, zinc and cadmium in environmentally exposed perch, Perca fluviatilis. AB - A field study of the role of metallothionein (MT) in the binding of heavy metals in perch (Perca fluviatilis), exposed to moderate levels of copper, zinc and cadmium, was performed. Perch were sampled at four sites in Sweden in September during two consecutive years. Two sites were located in the vicinity of a brassworks and two outside the emission range. The first year, fish from the two brassworks sites and from one of the uncontaminated sites were collected. The second year, fish from the most contaminated site and from the two uncontaminated sites were caught. The levels of hepatic copper, zinc and cadmium reflected the concentrations of these metals in water and were increased in fish from the two contaminated sites. The level of cadmium in liver was relatively low. MT was induced in liver of perch caught at the most contaminated site. The hepatic MT content in individual livers correlated well to the accumulation of copper (r = 0.85, P less than 0.001) and zinc (r = 0.75, P less than 0.001). There was a low but significant correlation between the levels of MT and cadmium in the liver (r = 0.48, P less than 0.001). The relationship between MT and metals was very similar both years. Subcellular fractionation of the metals in the liver revealed that an induction of MT was followed by an increased amount of copper, zinc and cadmium bound to the protein. The relative fraction of the total hepatic copper and cadmium bound to MT was increased at the most contaminated site, whereas there was no difference in subcellular distribution of zinc between the sites. In perch from the most contaminated site, the portions of hepatic copper, zinc and cadmium found in the cytosolic fraction were 70, 57 and 81%, respectively. Seventy-one % of the copper, 29% of the zinc and 84% of the cadmium found in hepatic cytosol of fish from the same site, eluted together with MT after gel filtration chromatography. The analysis of the subcellular distribution of copper, zinc and cadmium demonstrates that MT is responsible for the binding of a large amount of the total hepatic cellular content of copper and cadmium in perch. PMID- 1891446 TI - Studies on the lethal effect of ultraviolet light on Trichomonas vaginalis. AB - Following cultivation in Asami medium, centrifugation and resuspension in saline or in water from a medicinal spring, Trichomonas vaginalis trophozoites were exposed to well-defined doses of ultraviolet (UV) light (254 nm). We used 24- and 48-h-old trichomonads at concentrations of 1 x 10(5) and 5 x 10(4) trophozoites/ml in a total volume of 20 ml for these studies. The apparatus for UV irradiation was especially constructed for batch experiments. After irradiation at doses ranging from 80 to 160 mJ/cm2, the mobility of the parasites was reduced and morphological alterations appeared: rounding of the cells, vacuolization of the cytoplasm and even cytolysis. A dose of 401.7 mJ/cm2 killed 99.8% of the 48-h-old trichomonads when irradiation occurred in saline at a cell density of 1 x 10(5) trichomonads/ml and 98.9% when irradiation was done at a cell density of 5 x 10(4) trichomonads/ml. A dose of 362.1 mJ/cm2 killed only the more sensitive 24-h-old trichomonads. In mineral water, 241 mJ/cm2 was sufficient to kill up to 99.5% of the 48-h-old trichomonads. When 48-h-old trichomonads that had been exposed to a radiation dose of 160-240 mJ/cm2 were subcultured, they lost their ability to propagate. At a dose of 80 mJ/cm2, both the trichomonads that had been harvested during the log phase and the 48-h-old organisms suspended in mineral water lost their ability to propagate on subculture. These results indicate that 24-h-old trichomonads were more sensitive than 48-h-old organisms. Furthermore, the experiments demonstrated that a higher dose of UV radiation must be applied to T. vaginalis trophozoites than to the more sensitive bacterial strain Escherichia coli ATCC 11229 so as to achieve comparable killing results. PMID- 1891447 TI - Flow cytometric analysis of Eimeria tenella sporozoite populations exposed to salinomycin sodium in vitro: a comparative study using light and electron microscopy and an in vitro sporozoite invasion-inhibition test. AB - Eimeria tenella sporozoites exposed to 100, 70, 60 and 50 micrograms salinomycin sodium (SAL)/ml medium 199 at 41 degrees C and then stained with propidium iodide/fluorescein diacetate were analysed by means of flow cytometry (FCM). After 20 min exposure, they showed dose-dependent alterations in their size and shape, i.e. ballooning of most cells, and enhanced intracellular esterase activity as compared with untreated controls. After longer exposure periods (40 and 70 min), inflated cells gradually changed into shrivelled or crumpled, nonviable ones, thereby showing a gradual decrease in esterase activity and a gradual loss of membrane integrity (RFA+). As compared with untreated controls, sporozoites treated with 10 micrograms SAL/ml showed negligible RFA+ values (0.4% 2%), whereas those exposed to 1 and 0.1 microgram SAL ml and to the solvent dimethylsulfoxide (DMSO, 1%) did not, even after 70 min exposure. Slight to severe structural changes manifesting as an extremely wavy surface (1 microgram SAL/ml), vacuolization of the cytoplasm, distension or destruction of the mitochondrion and rupture of cell membranes (10 micrograms SAL/ml) were seen not only at higher SAL concentrations but also (rarely) at lower ones. The ability of sporozoites to invade primary chick-kidney cells was significantly inhibited by 70, 60 and 50 micrograms SAL/ml. In general, there were close relationships between findings obtained using FCM, electron microscopy and an invasion inhibition test. The results indicate that FCM is a reliable and sensitive technique for characterizing the parasiticidal effects on and the possible mode of action of drugs in free coccidian sporozoites. PMID- 1891448 TI - Ultrastructure of erythrocytes from Aotus trivirgatus and Saimiri sciureus monkeys infected by Plasmodium vivax. AB - Erythrocytes from Aotus and Saimiri monkeys parasitized by Plasmodium vivax show dramatic changes starting during the early stages of parasite development. Invaginations of the erythrocyte membrane, caveolae, are found during all parasite development stages. Up to six vesicles can be fused with one caveola, forming a caveola-vesicle complex. As the parasite grows, large accumulations of these vesicles can be seen within the erythrocyte cytoplasm. In addition to these caveolae-vesicle complexes, knob-like structures appear on the erythrocyte surface that are similar to those seen on the host-cell surface of P. falciparum infected red cells. Extensive membrane-bound clefts spread throughout the erythrocytic cytoplasm, sometimes forming stacks or large whorls. The density of the red cell cytoplasm begins to decrease at an early stage of parasite development. All of these changes may be responsible for an increased fragility of the P. vivax-infected red cell from Aotus or Saimiri monkeys. Moreover, the large amount of parasite material that is released during rupture of the red cell may account for the high fever paroxysms that are characteristic of P. vivax malaria infection. PMID- 1891449 TI - Life cycle of Hepatozoon mehlhorni sp. nov. in the viper Echis carinatus and the mosquito Culex pipiens. AB - Hepatozoon mehlhori sp. nov. and its developmental stages from the tissues of the Egyptian viper Echis carinatus and the mosquito Culex pipiens are described. The erythrocytic parasites were differentiated into the small form (trophozoite) measuring 14.5 +/- 0.6 x 4 +/- 0.12 micron and the mature form (gametocyte) measuring 17.2 +/- 1.6 x 5.4 +/- 0.5 micron. Merogony took place in the pulmonary endothelial cells and in the parenchyma cells of the liver and spleen of the infected vipers. Two types of meront were found. The large meronts (macromeronts) were 30.2 +/- 1.73 x 22.6 +/- 1.2 microns in size and yielded 16-40 (average, 28) micromerozoites measuring 17.2 +/- 0.7 x 5 +/- 0.15 microns. The small meronts (micromeronts) measured 18.2 +/- 0.6 x 13.5 +/- 0.5 microns and yielded 2-14 (average, 8) macromerozoites that were 15.1 +/- 0.12 x 6.2 +/- 0.8 microns in size. After syzygy in the haemocoel of the mosquito, the microgamont produced four uniflagellate microgametes (6.4 +/- 0.3 x 4.5 +/- 0.5 microns in size, with a short flagellum measuring 3.2 +/- 0.1 microns); on the 3rd day post-infection (p.i.)., one of these fertilized the macrogamete, giving rise to the zygote. The oocyst developed from the zygote on the 5th day p.i. and measured 135 +/- 2.6 x 120 +/- 1.8 microns. About 11-60 (average, 35) sporoblasts were formed by centripetal invaginations from each oocyst on the 8th day p.i. and developed into sporocysts on the 14th day p.i. Inside each sporocyst, 5-12 (average, 8) sporozoites, each measuring 12.6 +/- 1.2 x 4.1 +/- 0.3 microns, developed on the 16th day p.i. According to the above-mentioned characteristics the parasite was recorded as being a new species and was named Hepatozoon mehlhorni. Experimental transmission was accomplished by i.p. inoculation of the infectious stages (sporozoites) into uninfected vipers and led to the appearance of blood stages at 4-6 weeks p.i. PMID- 1891450 TI - Cellular reactions in the small intestine of rats after infection with Fasciola hepatica. AB - Groups of five rats each were infected with metacercariae of Fasciola hepatica according to two experimental procedures. In the first experiment, they received 20 metacercariae 0, 1, 2 or 3 times at intervals of 4 weeks. In the second, both the inoculation dose and the interval between doses were varied. After the animals had been killed, the small intestine was prepared for histology and tissue sections were stained for the detection and quantification of mucosal mast cells (MMCs), eosinophils and goblet cells. The density of eosinophils and MMCs increased significantly with each reinfection in the first experiment; in the second, the MMC reaction reached a peak at 4 weeks post-infection (p.i.), whereas the eosinophils peaked at 4 and 17 weeks p.i. In addition, the reaction of these cells depended on the infectious dose. In both experiments, goblet cells reacted only weakly. These findings thus clearly reflect a considerable intestinal response against migrating juvenile F. hepatica. The pattern of these defence reactions in the small intestine suggests some similarities with the mechanisms of antibody-dependent cell-mediated cytotoxicity that have been shown to take place during Schistosoma mansoni reinfection. PMID- 1891451 TI - Incidence, prevalence and geographic distribution of human alveolar echinococcosis in Austria from 1854 to 1990. AB - Since the second half of the last century it has been known that Austria--like southern Germany, eastern France and Switzerland--is a part of the Central European area of distribution of Echinococcus multilocularis (Em), the causative organism of alveolar echinococcosis (AE). Up until October 1990, 128 human AE cases were documented in Austria; personal, anamnestic and clinical data on the majority of these patients are available. Based on these data, epidemiological parameters (incidence, prevalence, geographic distribution, sex and age distribution, occupation) were evaluated so as to obtain information on the past and recent history of alveolar echinococcosis in Austria. The (retrospective) study led to the following results and conclusions: (a) the (documented) incidence (presently two cases/year) of AE in Austria is rather low; (b) the main endemic Em areas are situated in the western (Tyrol, Vorarlberg) and southern (Carinthia) provinces; (c) a new focus could be detected in Lower Austria (outside the Alps); (d) the sex ratio (M:F) of AE patients was 1.3:1; (e) the average age of men and women at the time of diagnosis was 44 and 47 years, respectively; (f) 98% of Austrian AE patients exhibited Em lesions in the liver; and (g) greater than 50% of AE patients were (or had been) farmers. PMID- 1891452 TI - Immunological recognition of larval Taenia crassiceps glycolipids by sera from parasite-infected mice. AB - The isolation and purification of a neutral glycolipid fraction from Taenia crassiceps metacestodes (KBS strain), harvested from both male and female NMRI mice at 70-80 days following intraperitoneal infection, revealed 24 thin-layer chromatography-designated glycolipid bands. The glycolipids were defined as ceramide mono- (n = 3), di- (n = 3), tri- (n = 4), tetra- (n = 5), and greater than tetrasaccharides (n = 9) according to their running properties as defined by thin-layer chromatography against standards of known structure. The defined glycolipids were tested for immunoreactivity with sera from noninfected and T. crassiceps-infected NMRI mice (intraperitoneal injection or implantation of 15 larvae/animal) using the enzyme-linked immunosorbent assay (ELISA) until day 33 p.i. (IgM and IgG reaction) and high-performance thin-layer chromatography (HPTLC) combined with immunostaining (IgG reaction) until day 7 p.i. ELISA determined IgM and IgG titres were significantly elevated from day 5 p.i. Immunostaining revealed early reactivity for certain ceramide tetra- and greater than tetrasaccharides (n = 6) on day 3 p.i. From day 5 p.i. onwards, nearly all glycolipids, including ceramide mono- and disaccharides, were recognized by the sera from metacestode-challenged mice. On day 7 p.i., a total of 22 bands were serologically active; of these, a considerable number (n = 10) showed increased staining intensity. Remarkably, in many cases (10 of 20), 3 glycolipids (tetra- and greater than tetrasaccharides) were weakly recognized by mouse sera taken before infection. PMID- 1891454 TI - Demonstration of regurgitation of gut content during blood meals of the tick Ornithodoros moubata. Possible role in the transmission of pathogenic agents. AB - Nymphs of Ornithodoros moubata were fed tritiated ecdysteroid. These ingested hormones are conjugated to fatty acyl esters that accumulate in the midgut (Connat et al. 1988). A few months later, the same ticks which had molted, were fed on physiological medium without radiolabel. At the issue of the blood meal, the nutritive medium contained an amount of radiolabel corresponding to 0.5% of the total labelling in the animal before the blood meal; this corresponded to 1.3% of the midgut content. These results demonstrate that in addition to transmission of parasites by saliva and coxal fluid (Burgdorfer 1951), transmission through regurgitation of the blood content in the gut could occur. An equivalent quantity of radiolabel was also emitted in the feces during and after the meal, but no conclusion about parasite transmission can be drawn from these "metabolic" results. PMID- 1891453 TI - The sheaths of Brugia microfilariae: isolation and composition. AB - Burgia malayi and B. pahangi microfilariae were isolated from the blood of infected Mastomys natalensis, and were exsheathed by freezing, thawing and agitation. Pure sheaths were obtained by a filtration procedure. The sheaths were found to contain about 95 mol% of amino acids, with proline, glutamic acid/glutamine, alanine, cysteine/cystine and glycine being the major components, and 5 mol% of carbohydrates, notably (N-acetyl)galactosamine, but no (N acetyl)glucosamine. PMID- 1891455 TI - Swiss Giardia isolates of different host origin show great similarities in their metabolism. PMID- 1891456 TI - Haemolysis of infected erythrocytes--a trigger for formation of Plasmodium falciparum gametocytes? PMID- 1891457 TI - Molecular recognition at the active site of subtilisin BPN': crystallographic studies using genetically engineered proteinaceous inhibitor SSI (Streptomyces subtilisin inhibitor). AB - Unlike trypsin-like serine proteases having only one conspicuous binding pocket in the active site, subtilisin BPN' has two such pockets, the S1 and S4 pockets, which accommodate the P1 and P4 residues of ligands (after Schechter and Berger notation) respectively. Using computer graphics, the geometrical nature of the two pockets was carefully examined and strategies for site-directed mutagenesis studies were set up against a protein SSI (Streptomyces subtilisin inhibitor), which is a strong proteinaceous inhibitor (or a substrate analogue) of subtilisin BPN'. It was decided to convert the P1 residue, methionine 73, into lysine (M73K) with or without additional conversion of the P4 residue, methionine 70, into glycine (M70G). The crystal structures of the two complexes of subtilisin BPN', one with the single mutant SSI (M73K) and the other with the double mutant SSI (M73K, M70G) were solved showing that (i) small 'electrostatic induced-fit movement' occurs in the S1 pocket upon introducing the terminal plus charge of the lysine side chain, and (ii) large 'mechanical induced-fit movement' occurs in the S4 pocket upon reducing the size of the P4 side chain from methionine to glycine. In both (i) and (ii), the induced-fit movement occurred in a concerted fashion involving both the enzyme and 'substrate' amino acid residues. The term 'substrate-assisted stabilization' was coined to stress the cooperative nature of the induced-fit movements. PMID- 1891458 TI - Solution conformation of endothelin determined by means of 1H-NMR spectroscopy and distance geometry calculations. AB - The structure of endothelin-1 (ET-1), an endothelial cell-derived peptide with vasoconstricting activity, was determined in an aqueous solution by means of a combination of NMR and distance geometry calculations. The resulting structure is characterized by an alpha-helical conformation in the sequence region, Lys9 Cys15. Furthermore, an extended structure and a turn structure exist in the Cys1 Ser4 and Ser5-Asp8 regions respectively, and no preferred conformation was found for the C-terminal part of the peptide which was not uniquely constrained by the NMR data. These structural elements, the alpha-helical structure in the sequence portion, Cys-X-X-X-Cys, and the extended structure in Cys-X-Cys, are homologous to those found commonly in several neurotoxic peptides. PMID- 1891459 TI - The solution structure of a leucine-zipper motif peptide. AB - We report the complete structure determination of a 34 residue synthetic peptide with the amino acid sequence of the dimerization domain (leucine zipper) of GCN4. A high resolution structure in solution was obtained by 1H-NMR studies and distance geometry calculations followed by restrained energy minimization. A set of 20 final structures was obtained with an average root mean square deviation of 1.3 A for the backbone atoms (excluding the first and the last two residues). The structure contains an uninterrupted helix. A comparison with a structure previously determined for a larger peptide containing both the DNA-binding region (basic region) and the leucine-zipper motif shows the structural independence of the leucine-zipper domain from the contiguous DNA binding region. PMID- 1891460 TI - Modelling of solvent positions around polar groups in proteins. AB - Previous analysis of the distribution of experimental solvent molecule positions around amino acid side chains showed that distinct clustering occurred close to polar or charged atoms in proteins. We have used those data to predict likely solvent positions around proteins not used in our initial analysis. We envisage that this algorithm, AQUARIUS, will be useful for finding solvent positions in electron density maps generated by protein crystallography and as useful starting positions for solvent molecules in computer simulation studies of macromolecules. PMID- 1891461 TI - Molecular model-building of amylin and alpha-calcitonin gene-related polypeptide hormones using a combination of knowledge sources. AB - Amylin is the major component of the amyloid found in the pancreases of noninsulin-dependent diabetics (type 2 diabetes). It is a 37 amino acid polypeptide and has been shown to have 46% sequence identity with the neuropeptide alpha-calcitonin gene-related peptide (alpha-CGRP). Both amylin and alpha-CGRP are known to be potent inhibitors of glycogen synthesis in stripped rat soleus muscle. Secondary structure prediction and tertiary structure model building show the two polypeptides to have an alpha-helix/beta-strand motif similar to that observed in the insulin B-chain. The results have been supported by CD spectroscopy, although there is no sequence similarity between insulin and amylin/alpha-CGRP. Aggregation states have been predicted based on the dimeric and hexameric arrangements seen in porcine insulin. Rat and hamster amylin have a changed sequence motif in the beta-strand which results in lack of amyloid formation and type 2 diabetes. This, we propose, is caused by disruption of hydrogen bonding which prevents the formation of the dimer. PMID- 1891462 TI - Intersubunit disulfide-bonded lambda-Cro protein. AB - Site-directed mutagenesis has been employed to substitute cysteine for valine at position 55, which is located on the dimer interface of the Cro protein of bacteriophage lambda. It has been found that the Cys55 Cro protein (Cro VC55) spontaneously forms a stable disulfide-bonded dimer in the absence of a reducing agent. UV-CD and NMR data showed that the mutant protein retains the conformation of the wild Cro protein and has acquired significant heat-stability. However, its specific DNA-binding activity is reduced several times compared with that of the wild Cro. Photochemically induced dynamic nuclear polarization (CIDNP) spectra demonstrated that a conformational change of Cro VC55 did not take place upon the formation of a complex with OR3, in contrast to the case of the wild Cro. These data suggest that the induced fitting, like loosening, of the two subunits of the wild Cro dimer contributes to the enhancement of its affinity to its operator DNA, which results in a specific interaction between Cro and OR3. PMID- 1891463 TI - The role of tyrosine residues in the DNA-binding site of the Pf1 gene 5 protein. AB - The 144 amino acid gene 5 protein of bacteriophage Pf1 binds tightly and cooperatively to single-stranded DNA during replication of the phage genome. It has been suggested that aromatic amino acid side chains are important for this interaction, probably through base stacking with the DNA. We have analysed the accessibility of tyrosine residues in the DNA-protein complex, and their importance to the DNA-binding activity of the protein, by chemical modification and protection experiments using tetranitromethane. Tyrosines 21, 30 and 55 are surface accessible in the free protein but are protected from modification in the complex with phage DNA. Moreover, modification of these residues in the free protein abolishes the ability to bind to DNA or oligonucleotides, as judged by fluorescence spectroscopy and gel retardation analysis. Modification of the protein also results in the formation of an intersubunit covalent cross-link between Tyr55 and Phe76, suggesting that Phe76 is located within the DNA-binding cleft of the protein. It is proposed that residues 17-34 of the Pf1 gene 5 protein form a beta-hairpin analogous to the 'DNA-binding wing' of the fd and Ike gene 5 proteins. We suggest the existence of a single-stranded DNA binding motif, in which Tyr30 of the Pf1 protein is equivalent to the functionally important Tyr26 of the fd gene 5 protein. PMID- 1891464 TI - Conformational stability of human skeletal tropomyosins modified by site-directed mutagenesis. AB - We have used human beta-tropomyosin produced in Escherichia coli and deletion mutants obtained by site-directed mutagenesis to analyse the conformational stability of this molecule under various experimental conditions. Protein engineering has allowed us to answer some questions raised by stability analysis of the wild-type tropomyosin. The complex pattern of denaturation is due neither to heterogeneity of the preparation nor to head-to-tail interactions. The N- and C-termini are not of importance for the thermal stability of the molecule. On the contrary, deletion of the 31 C-terminus amino acids leads to a dramatic decrease of the stability observed in guanidinium chloride. This lowering is interpreted as the participation of one more guanidinium chloride ions to the denaturation equilibrium. Analysis of the stability in presence of organic solvents reveals that acetonitrile and methanol induce opposite effects. Investigation of these effects by three methods (CD, fluorescence and electrophoresis that measure respectively the content in alpha-helix, the contact between the two strands and the strands exchange) leads to the conclusion that strand separation can precede the denaturation of the alpha-helix. PMID- 1891465 TI - Site-specific forced misincorporation mutagenesis using modified T7 DNA polymerase. AB - A new method for forced misincorporation site-specific mutagenesis is described. The method uses an exonuclease-deficient modified version of T7 DNA polymerase in the presence of one dNTP to force a misincorporation. Analysis by PAGE is used to monitor the efficiency of such misincorporation reactions. Brief extension of the terminally mismatched primer/template using the same enzyme in the presence of all four dNTPs is followed by chase/ligation using unmodified T7 DNA polymerase and T4 DNA ligase to give heteroduplex DNA. We have applied the method to mutagenesis of the Lac Z region of M13 and found that, using strand selection, efficiencies of mutagenesis at one site are greater than 50%. When the mutating dNTP is complementary to a neighbouring homopolymeric tract on the template, multiple mutation is observed and efficiences are lower. The method is more general than internal mismatch mutagenesis and, because of its rapidity, is more expedient than existing methods of forced misincorporation mutagenesis. PMID- 1891466 TI - Expression in Escherichia coli of a synthetic gene coding for horse heart myoglobin. AB - A gene for expression of horse heart myoglobin in Escherichia coli has been constructed in one step from long synthetic oligonucleotides. The synthetic gene contains an efficient translation initiation signal and used codons that are commonly found in E. coli. Unique restriction sites are placed throughout the gene. It has been inserted in a phagemid vector and is expressed from the lac promoter in E. coli at high efficiency, the soluble heme protein representing approximately 10% of soluble protein. Two versions of horse heart myoglobin were produced with aspartic acid or asparagine at residue 122. Comparison of chromatographic mobilities of these two proteins with authentic horse heart myoglobin identified aspartic acid as the correct residue 122. The availability of this gene, which is designed to facilitate oligonucleotide mutagenesis or cassette mutagenesis, will allow systematic structure-function analysis of horse heart myoglobin. PMID- 1891467 TI - A rapid and efficient method for site-directed mutagenesis by PCR, using biotinylated universal primers and streptavidin-coated magnetic beads. PMID- 1891468 TI - Prolactin and growth hormone in the regulation of the immune system. AB - Evidence implicating prolactin (PRL) and growth hormone (GH) in the regulation of the immune system has been reviewed. Hypophysectomized animals have deficiencies in both cell-mediated and humoral immunological functions and either PRL or GH corrects these deficiencies. Animals administered bromocryptine, a drug that specifically blocks PRL release, have impaired immune responses similar to hypophysectomized animals, and again both PRL and GH correct these deficiencies. Genetically dwarf animals, which lack both PRL and GH, are also immunocompromised, and once again PRL and GH can correct the deficiencies. In dwarf animals, however, fewer studies have examined PRL actions. In growth deficient children, immune function is not dramatically altered and basal secretion of GH has been reported. Very few clinical studies have examined whether PRL secretion is also deficient, and this may explain why a clear loss in immune function is not evident in growth-deficient children. In a number of species, including man, both PRL and GH stimulate thymic function and increase the secretion of thymulin, a thymic hormone. No studies, however, have reported on the effects of PRL and GH on other thymic hormones. A number of studies have reported in vitro effects of PRL and GH on cells involved with immunity, and the presence of high-affinity PRL and GH receptors have been observed on a number of these cells. The action of GH on the proliferative response of cells involved with immunity in vitro appears to be mediated by the production of insulin-like growth factor I. The effect of PRL on insulin-like growth factor I production by these cells has not been examined. One of the most consistent findings from in vitro studies is that prolactin antisera blocked a number of immune reactions. This led to the discovery that cells involved with immunity appear capable of producing PRL and GH, but the physiological significance of these observations have not been explored. There is a great need to identify the cell types responding to PRL and GH and this should be a goal of future investigations. There is also a need for investigators to be aware that both PRL and GH are involved in the regulation of the immune system and to design experiments to elucidate where each functions in the maturation cascade of cells involved with immunity. From the evidence available, it is apparent that PRL and GH have an important function in the immune system and future investigations should be directed toward elucidating their site(s) of action. PMID- 1891469 TI - The germ-free animal fed chemically defined diet: a unique tool. PMID- 1891470 TI - Influence of short-term maternal zinc deficiency on the in vitro development of preimplantation mouse embryos. AB - In this study, we evaluated the use of mouse preimplantation embryos as a model to study zinc deficiency-induced abnormal development. In Experiment 1, the effect of culture medium Zn concentrations on blastocyst development was studied. Preimplantation embryos (2 and 4 cells) obtained from superovulated females developed normally in media containing 0.7-30 microM Zn for up to 72 hr; higher levels of medium Zn resulted in abnormal development. In Experiment 2A, females were fed diets containing 50 (+Zn) or 0.4 (-Zn) micrograms Zn/g (760 vs 6 nmol/g, respectively) from 1 day before to 1 day after mating (3 days total). Preimplantation embryos were removed from the dams and cultured for 72 hr in 0.7 microM Zn medium. Embryos from the -Zn dams were morphologically normal at time zero; however, over the 72-hr period, these embryos tended to develop at a slower rate than controls, although compaction and cavitation frequency were similar. By the end of the 72-hr culture period, embryos from -Zn dams had significantly fewer cells than did embryos from control dams. In Experiment 2B, an extended period of maternal Zn deprivation (6 days) was used to investigate the potential for further impairment of in vitro preimplantation embryo development observed in Experiment 2A. Results from this experiment were consistent with those from Experiment 2A, in addition to providing evidence that the developmental progress of embryos obtained from mice fed Zn-deficient diets for 6 days was significantly impaired. In Experiment 3, the potential for supplemental Zn in culture medium to overcome the impairment in development due to maternal Zn deficiency was investigated. Embryos from female mice subjected to the same dietary regimen described in Experiment 2A were cultured to the blastocyst stage in medium containing Zn at a concentration of either 0.7 or 7.7 microM. Medium Zn supplementation did not improve development of embryos from dams fed Zn-deficient diets. In summary, embryos from mice fed -Zn diets for a 3- or 6-day period encompassing oocyte maturation and fertilization exhibited impaired development in vitro. This impairment was not overcome by medium Zn supplementation. PMID- 1891471 TI - Role of platelet-activating factor in renal function in normal rats and rats with bilateral ureteral obstruction. AB - Platelet-activating factor (PAF) is a powerful vasodilator with important effects on kidney function. It has been suggested that the renal effects of PAF are mediated by thromboxane A2 (TxA2). We examined the effect of PAF on renal function in sham-operated rats and rats that had undergone unilateral release of bilateral ureteral obstruction (BUO) of 24-hr duration, a condition in which the synthesis of TxA2 is increased. To eliminate systemic hemodynamic changes, PAF was infused directly into the left renal artery using the lowest dose that affected renal function (2.3 x 10(-13) moles/min). Infusion of PAF significantly decreased the glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) in normal rats and rats with BUO. Normal (sham-operated) rats pretreated with an inhibitor of TxA2 synthesis also had a significant decrease in GFR after administration of PAF (ERPF also decreased, but not significantly). Rats with BUO pretreated with an inhibitor of TxA2 synthesis had significantly greater basal GFR and ERPF (increases of 72 and 171%, respectively) than untreated BUO rats. Administration of PAF to the former group further increased GFR and ERPF (by 37 and 39%, respectively; P less than 0.001). The role of endogenous PAF was evaluated by administering a specific PAF receptor antagonist. Sham-operated rats pretreated with high doses of the PAF receptor antagonist had significantly higher mean arterial pressure values than normal untreated rats, and had no decrease in GFR and ERPF during PAF infusion. Rats with BUO pretreated with the PAF antagonist had a significant, dose-dependent decrease in basal GFR and ERPF. These data suggest that endogenous PAF has a vasodilatory role in obstructive nephropathy. No significant differences in eicosanoid excretion in the urine corrected per GFR were observed during infusion of PAF in any of the groups examined. In BUO rats with intact TxA2 synthesis, exogenous administration of PAF decreased renal function, presumably through further increases in the production of TxA2. However, when TxA2 production was inhibited, PAF administration increased GFR and ERPF, presumably due to its unopposed vasodilatory properties. The data suggest an important role of PAF in the hemodynamic changes seen in obstructive nephropathy. PMID- 1891472 TI - Inhibitory effect of alcohol on the established suckling-induced prolactin surge in lactating rats. AB - The effect of acute alcohol infusion on the established suckling-induced prolactin surge in lactating rats was examined. Dams were implanted with an atrial catheter on Day 6 of lactation and blood sampling was done on Day 10. Following the separation of litters from dams for a 6-hr period, a baseline blood sample was removed via a catheter extension. Pups were weighed and returned to dams. Subsequent blood samples were obtained 10, 30, and 60 min after initiation of suckling. Dams were then infused with alcohol doses of 0, 0.5, 1.0, 2.0, or 2.5 g/kg body wt. Infusion (0.1 ml/min) was completed in approximately 30 min. Additional blood samples were obtained 10 30, 60, and 120 min after the termination of infusion. In a separate group of rats, pups were removed from the dam after the first 60 min of suckling and additional blood samples were obtained 40, 70, 90, and 150 min after removal of pups (corresponding to 10-, 30-, 60-, and 120-min samples for rats infused with various alcohol doses). Alcohol, when administered after the establishement of suckling-induced prolactin surge and resulting in blood alcohol levels equal to or greater than legal human intoxication levels, inhibited prolactin release. However, continued suckling for an extended period (120 min in the present study) overcame this inhibitory effect, even when the blood alcohol level was comparable to (2.0 g/kg group) or greater than (2.5 g/kg group) the human legal intoxication level. Furthermore, in rats with established prolactin surges, the patterns of prolactin decline that followed alcohol administration or pup removal were comparable, indicating that similar mechanism(s) may be involved. PMID- 1891473 TI - Gender differences in the response of hepatic fatty acids and cytosolic fatty acid-binding capacity to alcohol consumption in rats. AB - To investigate possible gender differences in the response of hepatic fatty acids and cytosolic fatty acid-binding capacity to ethanol consumption, both female and male rats (41 days of age) were pair fed liquid diets (with a littermate of the same sex) for 28 days. The diets contained 36% of energy either as ethanol or as additional carbohydrate. After ethanol feeding, the hepatic concentration of fatty acids increased 155% in females (P less than 0.01), whereas there was only a trend for an increase (22%) in males. This was associated with a much smaller increase of cytosolic fatty acid-binding capacity in females (58%) than in males (161%). Whereas the ethanol-induced increase in fatty acid-binding capacity provided an ample excess of binding sites for the fatty acids in males, the increase in females was barely sufficient for the binding of the large increase of fatty acids produced by ethanol in the females. The cytosolic protein responsible for this binding, the liver fatty acid-binding protein of the cytosol (L-FABPc), also promotes esterification of the fatty acids. In keeping with the postulated role of this protein, the ethanol-induced increases in hepatic triacylglycerols, phospholipids, and cholesterol esters were smaller in females than in males. The gender difference in cholesterol esters was associated with parallel changes in acyl-CoA transferase activity. A possible implication of the relatively small and most likely inadequate increase in liver fatty acid-binding capacity and fatty acid esterification during alcohol consumption in the females is that under these circumstances the risk for development of a potentially deleterious accumulation of fatty acids in the liver is increased, thereby contributing to the enhanced vulnerability of females to alcohol-induced hepatotoxicity. PMID- 1891474 TI - Mechanism for enterohepatic injury caused by circulatory disturbance of hepatic vessels in the rat. AB - We reported previously that a transient occlusion followed by reperfusion of the portal vein and the hepatic artery of the rat significantly decreased the transhepatic transport of a cholephilic compound, and that this decrease was prevented by pretreating animals with poly(styrene co-maleic acid butyl ester) conjugated superoxide dismutase (SM-SOD). To elucidate the mechanism for oxidative injury of the liver and the site for the generation of superoxide radicals, the effect of a portosystemic bypass on the liver function was examined in the rat whose hepatic vessels were temporarily occluded. A portosystemic bypass inhibited the reperfusion-induced decrease in hepatic transport of bromosulfophthalein as effectively as did SM-SOD. Kinetic analysis using 125I labeled albumin revealed that the permeability of the small intestine markedly increased after a transient occlusion. The increase in intestinal permeability was also inhibited either by SM-SOD or by the portosystemic bypass. Xanthine oxidase activity in portal plasma markedly increased during occlusion and reperfusion, while it remained within normal ranges in the bypassed group. Thus, superoxide radical, and/or its metabolite(s), might play a critical role in increasing the intestinal permeability and in the pathogenesis of reperfusion induced liver injury. PMID- 1891475 TI - Serum glucose and free fatty acids modulate growth hormone and luteinizing hormone secretion in the pig. AB - Two experiments were conducted to determine the effect of free fatty acids (FFA) and glucose treatment on growth hormone (GH) and luteinizing hormone secretion in the pig. In Experiment (Exp) 1, 15 prepuberal gilts received an intravenous infusion of FFA (n = 5; 3 ml of 10% Liposyn II/kg), glucose (n = 5; 1 g/kg), or saline (n = 5; 3 ml of 0.9%/kg). Jugular blood samples were collected every 15 min for 2 hr before and 3 hr after intravenous infusion of saline, FFA, and glucose. Synthetic [Ala15]-h growth hormone-releasing factor-(1-29)NH2 (1 microgram/kg) and gonadotropin-releasing hormone (0.2 micrograms/kg) were administered 30 min after infusion (Time 0 = infusion). In Exp 2, eight prepuberal gilts received either FFA (n = 4) or saline (n = 4) as described in Exp 1, except that treatments were given every hour ove a 10-hr period. Blood samples were collected every 15 min from 1 hr before to 10 hr after the start of FFA or saline infusion. In Exp 1, the peak GH response to growth hormone releasing factor was delayed by 45 min (P less than 0.01) by glucose treatment and suppressed (P less than 0.01) by FFA treatment. The luteinizing hormone response to gonadotroph-releasing hormone was suppressed (P less than 0.03) by glucose and enhanced (P less than 0.03) by FFA. In Exp 2, the number of GH pulses was increased (P less than 0.05) by FFA infusion and GH concentrations were positively correlated (r = 0.58, P less than 0.0003) with FFA concentrations, while luteinizing hormone pulse amplitude was greater (P less than 0.01) in FFA gilts than in saline gilts. These results indicate that FFA are more effective modulators of GH secretion than acute hyperglycemia, while metabolic status can alter pituitary responsiveness to gonadotropin-releasing hormone. PMID- 1891476 TI - Thrombopoietin production in mice treated with acetylsalicylic acid. AB - Recent work revealed that mice in which platelet function was inhibited by acetylsalicylic acid (ASA) treatment showed evidence of increased platelet production. It was proposed that poorly functioning platelets gave rise to elevated thrombocytopoiesis by causing the release and action of thrombopoietin. However, direct evidence is lacking. Therefore, in the work reported here, plasma from mice treated with ASA was injected into normal recipient mice in an attempt to document the existence of the humoral factor. Compared with control mice given normal plasma, the injection of mice with plasma from ASA-treated mice resulted in increased thrombocytopoiesis, as evidenced by significant increases in the percentage of 35S incorporation into platelets, larger platelet size, and elevated megakaryocyte precursor cells (the small acetylcholinesterase-positive cell). For a positive control, additional mice were treated with plasma from animals made thrombocytopenic by an injection of antiplatelet serum. These mice also showed significant increases in thrombocytopoiesis. The results support the hypothesis that platelet production in ASA-treated mice is elevated by release and action of thrombopoietin. PMID- 1891477 TI - [Are drugs with anthranoid group harmful or non-harmful laxatives?]. PMID- 1891478 TI - [Quality of life in the aged--is it threatened by osteoporosis?]. PMID- 1891479 TI - Neuroendocrine rhythms. AB - Hormones are secreted with circhoral, circadian and seasonal periodicities. Circhoral pulsatility is a temporal code, many chronic and acute changes in neuroendocrine status being mediated by changes in the frequency of circhoral release. The identity of the neuronal circuits controlling circhoral release is not known. Circadian release of hormones occurs with a precise temporal order entrained to the light-dark cycle, synchronized to the activity/rest rhythm and generated by circadian oscillators, of which the suprachiasmatic nuclei are the most important. Seasonal rhythms are driven either by an endogenous circannual clock mechanism or by a process of photoperiodic time measurement which is dependent upon the duration of the nocturnal peak of the pineal hormone melatonin. PMID- 1891480 TI - The dynamics of drug resistance in Plasmodium falciparum. AB - Drug resistance of Plasmodium falciparum is not a recent phenomenon, but it became a major problem when the parasite became resistant to chloroquine, the cheapest and initially the most effective antimalarial compound that could be used for treatment and suppression. In some areas this problem is compounded by resistance to the first line of alternative drugs, and rapid loss of sensitivity to the next line. The dynamics of drug resistance are regulated mainly by drug related selection pressure and intensity of malaria transmission. Mass drug administration in its various forms, and insufficient treatment are obviously the most important motors of selection. PMID- 1891481 TI - Negative attitudes to clinical trials are not an external problem for clinical trials. PMID- 1891482 TI - Recurrent asystolia due to arrhythmic changes during treatment with lithium. PMID- 1891483 TI - Outcome criteria in antidepressant drug trials: self-rating versus observer rating scales. AB - An overview of the literature and some findings of the author's own empirical studies lead to the general conclusion that observer rating should be chosen as the principle outcome criterion in antidepressant drug trials. In various situations, however, self-rating scales can provide additional important information for therapy evaluation. The cross-sectional confirmity of observer ratings and self ratings of depression varies to a greater or lesser extent, depending on various background variables. With respect to longitudinal observation the relationship is much closer. Sensitivity for change can be attested not only to observer ratings but also to self ratings. PMID- 1891484 TI - Circadian variation in platelet imipramine binding during the day in healthy subjects. AB - Platelet tritiated imipramine binding values in healthy controls vary considerably from study to study. A possible contributor to such variation might be a circadian rhythm affecting binding, although previous studies of this have been contradictory. Platelet imipramine binding was examined in 12 healthy, medication-free subjects studied at 8 a. m., 11 a. m., 4 p. m., and 10 p. m. during one day. Imipramine binding was determined on platelet membranes, using 0.8-8 nM 3H-imipramine, and nonspecific binding was defined by 50 microM desipramine. All samples from a given individual were assayed simultaneously. The intra-assay coefficient of variation was 6.3 percent. There was no evidence of significant differences in binding capacity or affinity (Bmax or Kd) at different times of day. Circadian variation was explored using COSINOR analysis (DeMet et al., 1989). There was no evidence of circadian variation in binding using this model, even when only the variable portion of binding was considered for each individual. Intraindividual variation in binding was substantial, with a mean coefficient of variation of 29 percent for Bmax and 38 percent for Kd. The possible basis of this variation is unclear, but may reflect the presence of "occult" binding sites in the membrane, or the effect of endogenous modulators of binding. The interrelationship of Bmax and Kd may also be a factor. It was considered that low-affinity binding did not account for a significant part of the variation in Kd in this assay. The utility of imipramine binding as a biological marker of depression may be limited by such levels of intraindividual variation in binding parameters. PMID- 1891485 TI - Alprazolam and oxazepam in the treatment of anxious out-patients with depressive symptoms: a double-blind multicenter study. AB - In a four-week double-blind study comparing alprazolam with oxazepam, 62 outpatients suffering from anxiety with depressive symptoms were evaluated. The average daily doses of alprazolam and oxazepam were 1.48 mg and 44.4 mg, respectively. According to all rating scales applied, both alprazolam and oxazepam were effective in relieving anxiety associated with mild depression (p less than 0.01). Alprazolam proved somewhat more effective than oxazepam especially with regard to overall performance (p less than 0.05). Treatment emergent adverse effects were few and mild for both compounds tested. PMID- 1891486 TI - The action of clenbuterol on sleep and symptomatology in depressives. AB - Five female inpatients with major depression (melancholic type, DMS-III-R) were treated with the beta-adrenergic agonist clenbuterol for three weeks, with doses ranging from 100 micrograms to 150 micrograms. Remission of depressive symptomatology during treatment was observed in only one patient. All patients complained of side effects, especially tremor, agitation and restlessness. The sleep EEG showed no consistent effects on sleep parameters, including REM latency and percentage of REM sleep. Thus, the impact of clenbuterol on sleep clearly differs from that of most classical antidepressants. Regarding the lack of therapeutic efficacy, the data are compatible with the hypothesis of a relationship between REM sleep suppression and an antidepressant drug effect. Despite the small sample size, it can be concluded that clenbuterol is not likely to be a promising alternative to proven antidepressants in the treatment of major depression. PMID- 1891488 TI - Smoking-cessation treatment combining transdermal nicotine substitution with behavioral therapy. AB - Effects of smoking-cessation treatment combining transdermal nicotine substitution with behavioral therapy were investigated in two studies. A total of 403 smokers underwent nine weeks of behavioral self-control treatment. For seven weeks, groups with transdermal nicotine substitution were also provided with nicotine patches that continuously release nicotine through the skin into the circulatory system. The effects of treatment were measured by total abstinence. The results showed that the nicotine concentration in the patch, special relapse prevention methods, and the type of dosage (individual versus fixed dose) had no influence on therapeutic success. Nicotine concentration played a decisive role in the compatibility of the patch. Combining transdermal nicotine substitution with behavioral therapy produced 12-month success rates (total abstinence) of about 35%. PMID- 1891487 TI - Low melanin content of substantia nigra in a case of neuroleptic malignant syndrome. AB - A 19-year-old man suffering from a first episode of schizophrenia developed a neuroleptic malignant syndrome (NMS) after administration of haloperidol and levomepromazine. After five weeks of neuroleptic treatment he died of an unknown cause. Histological examination of the brain revealed a low melanin content in neurons in the substantia nigra (SN). Since neuromelanin in SN is the end-product of nonenzymatic dopamine degradation, the amount of melanin probably depends on the overall amount of dopamine produced during life. Thus, dopamine production must have been low in the reported case. In addition, ectopic neurons were found in subcortical white matter. PMID- 1891489 TI - Hypoglycemic effect of swerchirin from the hexane fraction of Swertia chirayita. AB - A xanthone was isolated from the hexane fraction of the Swertia chirayita plant and identified as 1,8-dihydroxy-3,5-dimethoxyxanthone (swerchirin). It has a very significant blood sugar lowering effect in fasted, fed, glucose loaded, and tolbutamide pretreated albino rat models. The ED50 for 40% blood sugar lowering in CF male albino rats (body weight 140-165 g) is 23.1 mg/kg/oral. The possibility of its application in clinical therapy for diabetes mellitus needs exploration. PMID- 1891490 TI - Neurotropic action of the hydroalcoholic extract of Melissa officinalis in the mouse. AB - A lyophilised hydroalcoholic extract of Melissa officinalis L. (Lamiaceae) has been evaluated for behavioral effects in mice. According to the traditional use of M. officinalis, sedative properties have been confirmed for low doses by the decrease of behavioral parameters measured in a non-familiar environment test (staircase test) and in a familiar environment test (two compartment test). With high doses, a peripheral analgesic activity was obtained by reducing the acetic acid-induced pain (writhing test); moreover, the plant extract induced the sleep in mice after treatment with an infrahypnotic dose of pentobarbital and potentialised the sleep induced by a hypnotic dose of pentobarbital. PMID- 1891491 TI - Hepatoprotective and anti-inflammatory effects of a traditional medicinal plant of Chile, Peumus boldus. AB - Dried hydro-alcoholic extract of Peumus boldus (Monimiaceae) has been evaluated for hepatoprotective, choleretic and anti-inflammatory effects in mice and rats, in order to validate or to invalidate traditional therapeutic indications. This extract exerted a significant hepatoprotection of tert-butyl hydroperoxide induced hepatotoxicity in isolated rat hepatocytes (in vitro technique) by reducing the lipid peroxidation and the enzymatic leakage of LDH; this in vitro efficacy was reinforced by a significant hepatoprotection on CCl4-induced hepatotoxicity in mice (in vivo technique), the plant extract reducing the enzymatic leakage of ALAT. Boldine, the main alkaloid of P. boldus appears to be implicated in this hepatoprotective activity. Choleretic effects, often mentioned in traditional indications, have not been confirmed in rats. Finally, significant and dose-dependent anti-inflammatory effects were obtained on an acute inflammatory process (carrageenan-induced edema test in rats). Boldine does not appear to be involved in such properties. PMID- 1891492 TI - The in vitro effects of griffonin and ouabain on erythrocyte sodium content obtained from normal subjects and sickle cell patients. AB - The in vitro effects of griffonin and ouabain on erythrocyte sodium content have been investigated in 6 normal subjects and 6 sickle cell patients. Intracellular sodium contents of normal or sickle cells incubated for 8 h in tris buffer, griffonin/tris buffer, or ouabain/tris buffer were determined. Incubation of normal cells in tris buffer or 0.5 mmol/l griffonin had little effect on the cell sodium content. However, 1.0 mmol/l griffonin/tris buffer raised the cell sodium level (P less than 0.05) over the incubation period. Ouabain/tris buffer (0.5 mmol/l or 1.0 mmol/l) also raised the sodium content (P less than 0.05 to P less than 0.001). Incubation of sickle cells in tris buffer raised the cell sodium (P less than 0.05) as did 0.5 mmol/l or 1.0 mmol/l griffonin (P less than 0.05 to P less than 0.001). Ouabain/tris buffer (0.5 mmol/l or 1.0 mmol/l) raised the intra erythrocyte sodium level (P less than 0.01 to P less than 0.001). These findings suggest that ouabain and griffonin both have similar actions on intra-erythrocyte sodium content although ouabain was more potent. It is suggested therefore that griffonin could be a useful anti-sickling drug for sickle cell disease crisis. PMID- 1891493 TI - Mechanism of anti-inflammatory action of glycyrrhizin: effect on neutrophil functions including reactive oxygen species generation. AB - The effect of glycyrrhizin on inflammatory mediators such as neutrophil functions including reactive oxygen species (ROS) generation was examined. Glycyrrhizin significantly decreased neutrophil-generated O2-, H2O2 and OH in a dose-dependent manner. However, the drug did not reduce any of the ROS generated in a cell-free, xanthine-xanthine oxidase system. The drug did not affect neutrophil chemotaxis or phagocytosis, either. The present study indicates that glycyrrhizin is not an ROS scavenger but exerts an anti-inflammatory action by inhibiting the generation of ROS by neutrophils, the most potent inflammatory mediator at the site of inflammation. PMID- 1891495 TI - Chemical properties and anti-complementary activities of heteroglycans from the leaves of Panax ginseng. AB - Four anti-complementary neutral (GL-NIa and GL-NIb) and acidic (GL-AIa and GL AIb) polysaccharides were purified from the leaves of Panax ginseng C. A. Meyer. Only GL-NIa and GL-AIa exhibited potent anti-complementary activities at low concentrations probably through the alternative complement pathway. Glycosyl linkage analysis demonstrated that GL-NIa mainly consisted of arabinogalactan moieties, whereas GL-NIb contained large amounts of (1----4)-linked glucosyl residues. Beta-Elimination indicated that GL-AIa and GL-AIb were pectic polysaccharides consisting of a rhamnogalacturonan core with neutral side chains. GL-AIa reacted strongly with beta-glucosyl-Yariv antigen, GL-NIa reacted weakly, whereas GL-NIb and GL-AIb showed no reaction with the antigen. PMID- 1891494 TI - Inhibition of mutagenesis and transformation by root extracts of Panax ginseng in vitro. AB - The root extract of Panax ginseng was investigated for its inhibitory effects on DNA synthesis, mutagenicity, and cellular transformation using V79 and NIH 3T3 cells. DNA synthesis measured by the [3H]thymidine incorporation into V79 Chinese hamster lung cells was significantly decreased by the addition of ginseng extract (0-1 microgram/ml) to the medium. However, ginseng extract was found to increase the rate of DNA excision repair synthesis in V79 cells in response to treatment with UV radiation or methyl methanesulfonate. The extract also showed decreased mutation frequency when mutagenicity was examined using V79 cells at the hypoxanthine-guanine phosphoribosyl transferase locus as resistance to 6 thioguanine after exposure to methyl methanesulfonate. We also found that the components of ginseng extract continue to exert an inhibitory effect on the transformation of NIH 3T3 cells initiated by 3-methylchloanthrene, methyl methanesulfonate, and 1-methyl-3-nitro-1-nitrosoguanidine. PMID- 1891496 TI - A new method for the in vitro screening of inhibitors of angiotensin-converting enzyme (ACE), using the chromophore- and fluorophore-labelled substrate, dansyltriglycine. AB - In our search for antihypertensive plant constituents, we developed a new in vitro assay for the detection of angiotensin-converting enzyme inhibitors in plant extracts. The chromophore- and fluorophore-labelled tripeptide dansyltriglycine is used as substrate, which is cleaved by the enzyme into dansylglycine and diglycine. The product dansylglycine and unreacted substrate are separated and quantified by reversed phase high performance liquid chromatography with UV detection. This target-directed enzyme assay is very specific, highly sensitive and reproducible, and lends itself very easily to automation. PMID- 1891497 TI - New indole alkaloid glycosides from Nauclea orientalis. AB - Two new indole alkaloid glycosides, 10-hydroxystrictosamide and 6'-O acetylstrictosamide, as well as the known alkaloids strictosamide and vincosamide were isolated from the leaves of Nauclea orientalis L. The structures of the isolated compounds were determined using spectroscopic methods, mainly 1D- and 2D NMR spectroscopy. PMID- 1891498 TI - Antifungal biphenyls from Monnina sylvatica. PMID- 1891499 TI - Friedelanes and triterpenoid quinone methides from Hippocratea excelsa. PMID- 1891500 TI - [A clinical study of schizophrenia associated with new religion in Japan]. PMID- 1891502 TI - [Refractory patient in Japanese psychiatry and criminal responsibility]. PMID- 1891501 TI - [Analysis of breakdown in family care for patients with dementia]. AB - Although it has been stressed that patients with dementia should be cared for at home, family care seems to break down sooner or later. On the other hand, the number of demented patients is now increasing at a far greater rate than can be handled by institutions for the elderly. For these reasons, the appropriate use of social resources is now being emphasized. As early as 1960, Macmillan pointed out that the emotional relationship between an elderly patient and the relative responsible for him determines whether family care will breakdown, and stressed the importance of troublesome behavior in this relationship. Since then, researchers have studied the problem of troublesome behavior in demented patients and the burden that this creates for relatives nursing them. Such studies have stressed that the support of caring relatives is indispensable for the community care of demented patients. In the present study an attempt was made to analyze in detail the breakdown of family care for demented patients. To facilitate systematic study, we complied a pair of check lists containing criteria of troublesome behavior and care burden, adapted from the Disability and Handicap criteria of the WHO. For the purpose of the study, we regarded troublesome behavior as Disability, and care burden as Handicap. The subjects were 40 demented patients and their respective main carers, who had requested institutional care. Before the breakdown, the author had been in charge of all of the patients. The mean period of patient observation was 12 months. At the point when the decision of institutionalization was made by family members, visits were made to each patient-carer pair, and the check lists were used to assess troublesome behavior and care burden. In order to clarify the features of the subject group, the author also visited and examined another 30 patient-carer pairs, who still lived in their home communities, between June and September, 1990. The mean period of observation for these patients was 18 months. There were no significant differences in sex, diagnosis, duration of illness, cognitive function, or number of physical complications between the two groups. No significant difference was found in the total score for the behavior check list between the two groups. In contrast, however, there was a significantly higher score for the burden check list representing those caring for the patients in the study group. Furthermore, it was revealed that social activity, individual free time and familial interaction, as well as many emotional and physical aspects, were more severely affected in the subject carers. This result appeared to confirm that the care burden itself, rather than troublesome behavior is responsible for breakdown. In all of the 70 pairs analyzed, a significant correlation was found between the total score for the behavior check list and that for the burden check list. The result of this study highlighted several new emerging problems. One serious problem is that of patients driving by themselves. In addition, many of carers reported recurrent falls by the patients. As to the problems faced by carers themselves, an appreciable number had been forced to give up their jobs to devote themselves to patient care. In general, female carers with husbands younger than 65 years reported economic distress. Additionally, unlike the situation in most western reports, as many as 43% of the main carers in this study were daughters in law. These problems faced by carers seem to be common in Japan, and are perhaps characteristic of Japanese society.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1891503 TI - [Persons liable for protection of the mentally disordered and their civil responsibility]. PMID- 1891504 TI - [NIMH--grant and research system]. PMID- 1891505 TI - Evaluating cognitive impairment in depression with the Luria-Nebraska Neuropsychological Battery: severity correlates and comparisons with nonpsychiatric controls. AB - Depressed patients often complain of memory and attentional difficulties, and some research suggests an increased incidence of neuropsychological impairment in depression. Yet, many prior studies contain methodological problems, including the following: (1) inclusion of medicated patients, (2) small sample sizes, and (3) tests with unknown psychometric properties. We administered the Luria Nebraska Neuropsychological Battery (LNNB) to 28 unmedicated inpatients who met Research Diagnostic Criteria for major depression. Twenty of the 28 patients were given additional cognitive measures (e.g., Wechsler Adult Intelligence Scale Revised, Benton Tests). The depressed patients performed similarly to an age- and education-matched nonpsychiatric reference sample. When data for a subset of the most severely depressed patients were analyzed separately, these patients too were found to perform similarly to matched controls. There were no relationships between Hamilton rating scale measures of depression severity and any cognitive measures among the depressed patients. The results suggest that cognitive functioning in depressed patients does not differ significantly from that in carefully matched controls and is independent of symptom severity. PMID- 1891506 TI - Neuropsychological performance in adults with Tourette's syndrome. AB - Neuropsychological performance was examined in a sample of 36 adults who met DSM III-R criteria for Tourette's syndrome (TS), confirmed by a psychiatrist or a neurologist. All subjects were administered an extensive battery of psychological and neuropsychological tests as well as symptom rating scales. The mean performance on most tests was within normal limits, and the patients and controls did not differ on a summary measure of neuropsychological performance. However, apparently 20% of the TS subjects had mild abnormalities on a summary measure of neuropsychological performance. These data are consistent with recent reports of generally normal performance in children with TS. Poor performance on several tasks was related to later age at symptom onset. The results were discussed with regard to the nature of the sample and directions for future research. PMID- 1891507 TI - Cortisol hypersecretion in depressed school-aged children and adolescents. AB - A prospective longitudinal study has been carried out to determine the secretory pattern of cortisol in children (n = 10) with major depressive disorder. Salivary cortisol samples were collected at 4-hourly intervals over 24 hours when the subjects were depressed and again when they were recovered. Group comparison indicated that significant increases in mean cortisol output occurred during illness as compared with recovery. This difference occurred only at three points (midnight, 4 a.m., 8 a.m.) of six measured. Not all cases were showed hypersecretion, but when hypersecretion was present, it occurred in cases with more severe symptoms. In addition, marked differences existed within individuals in the depressed state vs. the recovered state. Hypersecretion appeared to be associated with a significant alteration in diurnal rhythm in some, but not all, cases. The degree of cortisol responsivity and the shape of the curve over 24 hours during the depressed state deserve further investigation and may have implications for the course and outcome of major depression in this age group. PMID- 1891508 TI - Clinical, cognitive, and demographic predictors of response to cognitive therapy for depression: a preliminary report. AB - This preliminary study evaluated prognostic indicators or predictors of response to cognitive therapy. The sample included 37 unipolar outpatients with moderate to severe major nonpsychotic depressive disorder, according to Research Diagnostic Criteria. Demographic characteristics (sex, age, marital status, and education), pretreatment severity measures (Hamilton Rating Scale for Depression [HRSD] and Beck Depression Inventory [BDI]), pretreatment cognitive measures (Dysfunctional Attitudes Scale [DAS] and Attributional Style Questionnaire Failure Composite [ASQ-F]), and historical features (length of illness, length of current episode, number of episodes, and age of onset) were used in multiple regression models to predict response. In accord with previous findings, patients who had higher (rather than lower) pretreatment HRSD, BDI, or DAS scores and were single (rather than married) showed a poorer response to cognitive therapy, according to the HRSD. Furthermore, married outpatients with high DAS scores or single patients with low DAS scores showed an intermediate response to cognitive therapy, while single patients with high DAS scores responded the least. Generally, effects were stronger when response was assessed according to clinician-rated severity measures rather than patient self-reports. PMID- 1891509 TI - Serotonin receptor sensitivity and aggression. AB - This study investigated the relationship between increased serotonin (5 hydroxytryptamine, 5HT) receptor sensitivity and human aggression. A low oral dose of meta-chlorophenylpiperazine (MCPP), a postsynaptic 5HT receptor agonist, was administered in a placebo-controlled design to depressed (n = 22) and panic disorder (n = 20) patients classified with or without signs of outwardly directed aggression, patients with a history of suicide attempts (inwardly directed aggression) (n = 11), and normal controls (n = 19). Hormones under 5HT control were measured at 30-min intervals. Results were as follows: (1) MCPP did not induce or reduce anger, (2) patients with outwardly directed aggression did not have significantly greater MCPP-induced cortisol or prolactin release than did patients without signs of outwardly directed aggression, (3) patients with a history of suicide attempts did not have significantly greater MCPP-induced cortisol or prolactin release than did normal controls, and (4) MCPP-induced hormone release was unrelated to measures of aggression. PMID- 1891510 TI - Prediction of social skill acquisition in schizophrenic and major affective disorder patients from memory and symptomatology. AB - Memory and symptomatology were examined as predictors of social skill acquisition in psychiatric inpatients participating in a social skills training program. Poor memory was related to pretreatment social skill impairments and slower rates of skill improvement during the intervention for patients with schizophrenia or schizoaffective disorder, but not affective disorder. Symptomatology was not consistently related to pretreatment social skill or changes in skill for either schizophrenic or affective disorder patients. The results suggest that cognitive deficits in schizophrenia are associated with impairments in social skill and that such deficits may limit the rate of skill acquisition and clinical response to social skills training interventions. PMID- 1891511 TI - Abnormal growth of skin fibroblasts from schizophrenic patients. AB - Fibroblast cultures were established from skin biopsies of 18 schizophrenic patients (14 on drug and 4 off drug) and 13 normal subjects, and growth parameters (initial growth and rate of growth) and morphology were studied. Fibroblasts from patients took significantly longer to grow than did normal fibroblasts. Cell lines were established within 2 weeks for all normal controls, but for only 6 (33%) of 18 schizophrenic patients. The rate of growth (doubling time) was also significantly longer for fibroblasts from patients than from normals. Neither time to establishment of initial growth nor doubling time was related to age, sex, age at onset, duration of illness, or medication status in the patients. Fibroblasts from normals showed uniform, long (slender), characteristic spindle-like, bipolar appearance, with unidirectional orientation, both while growing from explant as well as after subculturing. By contrast, fibroblasts from patients generally showed random size (shorter and flatter), mostly spiny, multipolar cells with short stubby projections, and an irregular orientation resulting in a criss-cross pattern, and often exhibited poor attachment. Fibroblasts from skin biopsies of patients who were drug free at the time of biopsy showed similar initial growth, doubling time, and morphology to those from patients who were receiving neuroleptic treatment. In vitro challenge of skin biopsies of normal subjects with haloperidol in culture resulted in slight delay in initial growth and marginal increase in doubling time. However, the morphology remained normal. Possible molecular mechanisms that may be associated with abnormal growth of fibroblasts in schizophrenia are discussed. PMID- 1891512 TI - Plasma catecholamines and their metabolites in obsessive-compulsive disorder. AB - Plasma catecholamines and their metabolites were sampled in 13 medication-free patients with obsessive-compulsive disorder (OCD) and 29 normal controls. In addition to severe OCD symptoms, the patients had significantly higher anxiety, tension, and resting pulse rates than the controls. Nonetheless, mean plasma concentrations of norepinephrine (NE) and epinephrine (E), the catecholamine metabolites 3-methoxy-4-hydroxyphenylglycol (MHPG) and homovanillic acid (HVA), and the stress-related hormone cortisol did not differ between OCD patients and normal controls. When the patients and control populations were combined and average plasma NE and E levels calculated over 35 min, subjects with a higher mean NE output (greater than 1.1 pm/ml) had higher Profile of Mood States depression scores than subjects with a low NE output (less than 1.1 pm/ml). Altogether, these results indicate that elevated plasma catecholamine measures are not likely to be associated with the pathophysiology of OCD. PMID- 1891513 TI - A high risk study of young children of parents with panic disorder and agoraphobia with and without comorbid major depression. AB - Using family study methodology and psychiatric assessments by blind raters, this study tested hypotheses about patterns of familial association between anxiety and depressive disorders among high risk children of clinically referred parents. The study design contrasted five groups of children defined by the presence or absence in a parent of (1) panic disorder and agoraphobia (PDAG) without comorbid major depressive disorder (MDD) (n = 14); (2) comorbid PDAG plus MDD (PDAG + MDD) (n = 25); (3) MDD without comorbid PDAG (n = 12); (4) other psychiatric disorders (n = 23); and (5) normal comparisons (n = 47). While the PDAG and PDAG + MDD groups had similarly elevated rates of anxiety disorders and MDD, offspring of MDD parents had an elevated rate of MDD but not of anxiety disorders. Among children of parents with PDAG + MDD, the presence of an anxiety disorder did not significantly increase the risk for MDD in the same child. Thus, anxiety and MDD did not cosegregate among children of PDAG parents. These findings indicate that parental PDAG, either alone or comorbidly with MDD, increases the risk for both anxiety and depressive disorders in offspring. In the absence of PDAG, however, parental MDD does not appear to place children at risk for anxiety disorders. These findings are most consistent with the hypothesis that PDAG and PDAG + MDD share common familial etiologic factors while MDD alone is an independent disorder. More studies are needed to confirm these preliminary findings as well as to identify mediating factors that influence the transition from childhood to adult anxiety disorders. PMID- 1891514 TI - What can specificity designs say about causality in psychopathology research? AB - Specificity designs in psychopathology research are used to examine whether a variable is unique to a given disorder. When nonspecificity is observed, it typically is assumed that the variable in question is not a cause of the disorder, but is instead a nonspecific consequence of general psychopathology. Such reasoning is flawed, however, because it fails to distinguish between testing a particular causal model containing the variable versus testing the causal status of the particular variable within the model. A variable may be nonspecific, but still causal, if it is one of several multiple interacting causes or if a nosological error has been made. A recognition of these complexities has implications for the nature of the psychopathology control group selected. PMID- 1891515 TI - Alcoholism and memory: broadening the scope of alcohol-expectancy research. AB - Current biopsychosocial research on the etiology of alcoholism has begun to focus on memory processes as a possible common pathway for drinking decisions. The alcohol-expectancy construct is rooted both in cognitive psychology and alcohol research and can serve as a vehicle for this study. Reexamination of one recent review of issues in alcohol-expectancy research provides an opportunity to broaden the scope of this research with theoretical and methodological alternatives to those suggested in that review. Most importantly, this article shows that expectancy findings, discussed by Leigh (1989a) as reflecting "psychometric" limitations, are instead quite consistent with recent network models of memory structure. Such models can provide an informative guide to future research activities. It is also recommended that alcohol-expectancy research remain open to inputs from expectancy theories already developed in several psychological domains, as well as to theories of social cognition and attitude structure in addition to those advanced by Leigh. PMID- 1891516 TI - On the scope of alcohol expectancy research: remaining issues of measurement and meaning. AB - An article by Leigh (1989d) examined certain substantive and measurement-related limitations of research on alcohol outcome expectancies. Leigh (1989d) criticized research in this field on both conceptual and methodological grounds and speculated on future theoretical directions for research in the field. In their response, Goldman, Brown, Christiansen, and Smith (1991) contended that Leigh's critique is faulty in important respects. However, some of their points are based on misinterpretations of Leigh's comments, and they appear to have insufficient appreciation of conditions necessary for comprehensive measurement validation and for meaningful application of theories of memory to alcohol expectancy research. Despite the limitations of expectancy research, exciting avenues exist for further work. PMID- 1891517 TI - The affective organization of parenting: adaptive and maladaptive processes. AB - This article presents a 3-component model of parenting that places emotion at the heart of parental competence. The model emphasizes (a) child, parent, and contextual factors that activate parents' emotions; (b) orienting, organizing, and motivating effects that emotions have on parenting once aroused; and (c) processes parents use to understand and control emotions. Emotions are vital to effective parenting. When invested in the interest of children, emotions organize sensitive, responsive parenting. Emotions undermine parenting, however, when they are too weak, too strong, or poorly matched to child rearing tasks. In harmonious relationships emotions are, on average, positive because parents manage interactions so that children's and parents' concerns are promoted. In distressed relationships chronic negative emotion is both a cause and a consequence of interactions that undermine parents' concerns and children's development. PMID- 1891518 TI - Do parent-child relationships change during puberty? AB - This article reviews changes in parent-child relationships during puberty, emphasizing the developmental processes that might be implicated in these changes. Evidence suggests increases in conflict and less warm interactions in relationships between parents and children during puberty. Changes are assumed to be short term, although little longitudinal research has directly addressed the issue of long-lasting effects. Other developmental changes occurring for the adolescent, the parent, or both (such as social cognitive or self-definitional change), as well as other relationship changes, personality characteristics, and the sheer number of life events or transitions have all been posited as potential contributors to changes in the parent-child relationship for young adolescents. These possible contributors, however, have seldom been studied in conjunction with pubertal changes. Such integrative research is necessary to test various models through which puberty, social relationships, social cognitive, self definitional, and other processes influence one another and are influenced by one another during the transition to adolescence. PMID- 1891519 TI - Asymmetrical effects of positive and negative events: the mobilization minimization hypothesis. AB - Negative (adverse or threatening) events evoke strong and rapid physiological, cognitive, emotional, and social responses. This mobilization of the organism is followed by physiological, cognitive, and behavioral responses that damp down, minimize, and even erase the impact of that event. This pattern of mobilization minimization appears to be greater for negative events than for neutral or positive events. Theoretical accounts of this response pattern are reviewed. It is concluded that no single theoretical mechanism can explain the mobilization minimization pattern, but that a family of integrated process models, encompassing different classes of responses, may account for this pattern of parallel but disparately caused effects. PMID- 1891520 TI - Binge eating as escape from self-awareness. AB - This article proposes that binge eating is motivated by a desire to escape from self-awareness. Binge eaters suffer from high standards and expectations, especially an acute sensitivity to the difficult (perceived) demands of others. When they fall short of these standards, they develop an aversive pattern of high self-awareness, characterized by unflattering views of self and concern over how they are perceived by others. These aversive self-perceptions are accompanied by emotional distress, which often includes anxiety and depression. To escape from this unpleasant state, binge eaters attempt the cognitive response of narrowing attention to the immediate stimulus environment and avoiding broadly meaningful thought. This narrowing of attention disengages normal inhibitions against eating and fosters an uncritical acceptance of irrational beliefs and thoughts. The escape model is capable of integrating much of the available evidence about binge eating. PMID- 1891521 TI - A general theory concerning the prenatal origins of cerebral lateralization in humans. AB - The origins of cerebral lateralization in humans are traced to the asymmetric prenatal development of the ear and labyrinth. Aural lateralization is hypothesized to result from an asymmetry in craniofacial development, whereas vestibular dominance is traced to the position of the fetus during the final trimester. A right-ear sensitivity advantage may contribute to a left-hemispheric advantage in speech perception and language functions, whereas left-otolithic dominance may independently promote right-sided motoric dominance and a right hemispheric superiority in most visuospatial functions. The emergence of handedness is linked to the assumption of an upright posture in the early hominids, whereas the failure to develop clear vestibular asymmetry may underlie the poor motoric lateralization found in several neurodevelopmental disorders. PMID- 1891522 TI - Preattentive recovery of three-dimensional orientation from line drawings. AB - It has generally been assumed that rapid visual search is based on simple features and that spatial relations between features are irrelevant for this task. Seven experiments involving search for line drawings contradict this assumption; a major determinant of search is the presence of line junctions. Arrow- and Y-junctions were detected rapidly in isolation and when they were embedded in drawings of rectangular polyhedra. Search for T-junctions was considerably slower. Drawings containing T-junctions often gave rise to very slow search even when distinguishing arrow- or Y-junctions were present. This sensitivity to line relations suggests that preattentive processes can extract 3 dimensional orientation from line drawings. A computational model is outlined for how this may be accomplished in early human vision. PMID- 1891523 TI - Categories and particulars: prototype effects in estimating spatial location. AB - A model of category effects on reports from memory is presented. The model holds that stimuli are represented at 2 levels of detail: a fine-grain value and a category. When memory is inexact but people must report an exact value, they use estimation processes that combine the remembered stimulus value with category information. The proposed estimation processes include truncation at category boundaries and weighting with a central (prototypic) category value. These processes introduce bias in reporting even when memory is unbiased, but nevertheless may improve overall accuracy (by decreasing the variability of reports). Four experiments are presented in which people report the location of a dot in a circle. Subjects spontaneously impose horizontal and vertical boundaries that divide the circle into quadrants. They misplace dots toward a central (prototypic) location in each quadrant, as predicted by the model. The proposed model has broad implications; notably, it has the potential to explain biases of the sort described in psychophysics (contraction bias and the bias captured by Weber's law) as well as symmetries in similarity judgments, without positing distorted representations of physical scales. PMID- 1891524 TI - Homeostatic theory of drug tolerance: a general model of physiological adaptation. AB - At the heart of homeostatic theory is the idea that explicit or implicit behavioral demands placed on physiological systems are required for the biological detection of homeostatic disturbances. The detection of drug-induced disturbances is required to drive the development of all systemic tolerance, both associative and nonassociative (i.e., both forms of tolerance are behaviorally contingent). A wide range of findings ranging from morphine-induced analgesia to ethanol-induced hyposexuality shows that contingent tolerance is pervasive and may be universal. The theory also stipulates that behavioral demands placed on the target system will govern the loss of both associative and nonassociative tolerance (physiological). The present formulation integrates contingent, associative, and nonassociative tolerance and drug-opposite withdrawal reactions within a unified theory. PMID- 1891525 TI - A critical review of Luneburg's model with regard to global structure of visual space. AB - Visual space (VS) is a coherent self-organized dynamic complex that is structured into objects, backgrounds, and the self. As a concrete example of geometrical properties in VS, experimental results on parallel and (equi) distance alleys in a frameless VS were reviewed, and Luneburg's interpretation on the discrepancy between these 2 alleys was sketched with emphasis on the 2 hypotheses involved: VS is a Riemannian space of constant curvature (RCC) and the a priori assumed correspondence between VS and the physical space in which stimulus points are presented. Dissociating these 2 assumptions, the author tried to see to what extent the global structure of VS under natural conditions is in accordance with the hypothesis of RCC and to make explicit the logic underlying RCC. Several open questions about the geometry of VS per se have been enumerated. PMID- 1891527 TI - Association between war and suicide and homicide. PMID- 1891526 TI - Mental health locus of control in agoraphobia and depression: a longitudinal study of inpatients. AB - This study represents a longitudinal extension for 75 inpatients of a previous cross-sectional study, wherein agoraphobic inpatients, both depressed and nondepressed, attributed mental health locus of control more to chance than non anxious depressed inpatients. This difference regarding chance locus of control persisted across posttest and one-year follow-up. At pre- and posttest, but not at follow-up, the group differences regarding externality to chance could be reduced to differences in reported fear of fear. Mental health locus of control scores exhibited moderate to high stability across assessments. Pretreatment level and during-treatment change of externality to chance did not predict proneness to relapse after treatment. Both a vulnerability model and a symptom model of the relation between externality to chance and agoraphobia received some support. On the other hand, reductions in internality during treatment predicted posttreatment relapse. Locus of control variables were also associated with effectiveness of treatment and posttreatment course, both with respect to fear of fear and to depression. PMID- 1891528 TI - The injustice of nonjudicial remedies to address childhood violence. AB - The hypothesis that nonjudicial remedies such as mediation, negotiation, and "fair fighting" are effective tools for use in dealing with childhood violence has enjoyed some speculation in recent years. This work evaluates the hypothesis that such methods are unjust to the victims of such violence and that these methods must be abandoned in favor of appropriate punishment for aggressors. PMID- 1891529 TI - Measurement and interrelations of psychiatric symptomatology in inpatients. AB - For 152 psychiatric inpatients scores on the Beck Depression Scale, State form of the State-Trait Anxiety Inventory, the Self-report Inventory, Hopelessness Scale and 3 MMPI scales, Hypochondriasis, Schizophrenia, and Hypomania, were factor analyzed. The two factors appeared to confirm Gotlib's 1984 suggestion that such questionnaires measure general distress, as responding endorses negative affect. PMID- 1891530 TI - Test-retest reliability of the Revised Self-monitoring Scale over a two-year period. AB - The Revised Self-monitoring Scale of Lennox and Wolfe was administered to 83 staff nurses in 1987 and in 1989 as part of on-going research. Test-retest correlations were: for Factor A, Ability to Modify Self-presentation, .53, for Factor B, Sensitivity to the Expressive Behavior of Others, .52, and for the Total Self-monitoring Score .55. These scores were sufficiently strong to warrant continued, but cautious use of this revised test. PMID- 1891531 TI - Private self-consciousness: does it influence convergent and discriminant validity of self-reported anxiety and depression? AB - A continuing problem in measurement of anxiety and depression with self-report is lack of discriminant validity. It is argued that private self-consciousness might be expected to be related to both convergent and discriminant validity of self reported anxiety and depression. Several self-report measures of anxiety and depression were administered to 157 female undergraduates, ages 20 to 36 years, but no evidence was found for a moderating influence of private self consciousness. The possibility of lack of correspondence between private self consciousness and self-awareness with regard to attentiveness to internal states is discussed as a possible explanation. PMID- 1891532 TI - Intellectual functions and personality in subjects with noncongenital myotonic muscular dystrophy. AB - Mental retardation and personality disorders are commonly described among the symptoms of myotonic dystrophy. Nevertheless, this tendency is not supported by systematic studies performed on large samples, whose results are controversial. We studied the cognitive functions and personalities of a group of 28 patients, in whom myotonic dystrophy had commenced in juvenile or adult life. The severity of the disease was variable, but all subjects were self-sufficient. Only 7.1% of subjects showed low intelligence with deterioration of perceptual-motor functions. This was not correlated with the severity of their disease. Women had a substantially lower mean Wechsler-Bellevue score than men. The personality function study of the entire group showed no change of psychiatric relevance but did present a depressive attitude with marked somatic concern and difficulties in establishing relationships in social life. PMID- 1891533 TI - Nurses' attitudes, nurse-patient interactions and adherence to treatment by hemodialysis patients. AB - Relationships among fluid intake and dietary-adherence of 29 hemodialysis patients, nurses' attitudes (liking-disliking) toward these patients, and selected nurses' and patients' verbalizations during hemodialysis treatment were explored. No significant associations were found. Nurses may be facilitating positive solutions to all patients' health care problems rather than admonishing those whom they dislike and/or who do not adhere to treatment. PMID- 1891534 TI - Psychological stress and gastric emptying in normal subjects. AB - Gastric emptying half-time was measured in 10 healthy volunteers on two different occasions over a one-week interval, with an identical test meal. The first was the control evaluation, and at the second assessment, psychological stress was induced by the technique of dichotomous listening. Psychological and physiological parameters were assessed before and during the test period. No significant or consistent modifications of gastric-emptying time were induced by the stress procedure. Looking at individual subjects instead of mean values, gastric emptying was unchanged in 5 subjects, slower in 3, and faster in the remaining 2. These 3 groups had different mean values on two subscales of the Sixteen Personality Factor Questionnaire. PMID- 1891535 TI - Relationship of the children's form of the Rosenzweig Picture-Frustration Study to children's behavior, gender, and fantasies. AB - To examine the validity of the Children's Form of the Picture-Frustration (P-F) Study, the instrument was administered to 245 children in Grades 1 through 6. Children were also administered the Make A Picture Story (MAPS) and the Response Hierarchy Measure. Teachers rated children's aggression on the Conners Teacher Rating Scale. Hostile responses on the P-F Study were related to self-reported verbal and physical aggression in conflict situations but were unrelated to teachers' ratings of aggressive behavior. Hostile responses were exhibited more often by boys than girls. Responses on the measure were related to children's fantasy patterns. Results supported the validity of the P-F Study as a measure of children's thought content in response to frustration. PMID- 1891536 TI - Loneliness among Korean and American university students. AB - Korean and American university students were compared on the Differential Loneliness Scale. The 70 Koreans scored as more lonely than the 213 Americans, while all were living away from home. PMID- 1891538 TI - Atenolol treatment of paruresis. AB - Atenolol, a cardioselective beta blocker, was administered following unsuccessful treatment with propranolol to a male with a significant history of paruresis. During atenolol therapy, the client reported a decrease in ANS symptoms but no increase in ability to urinate in public restrooms. Rationale for use of atenolol is discussed. PMID- 1891537 TI - Contributions to the history of psychology: LXXIX. Psychology's first publicist: H. Addington Bruce and the popularization of the subconscious and power of suggestion before World War I. AB - Between 1903 and America's entrance into World War I, journalist and psychologist H. Addington Bruce wrote numerous articles and books about psychology for the lay reader. At a time when widespread differences existed between psychologists as to subject matter and methods of study, he cultivated a decidedly Progressive image of psychology dominated by the concepts of the subconscious and power of suggestion. In contrast to the more hereditarian and materialistic assumptions embraced by most academic psychologists, Bruce's promotion of the importance of the environmentalistic and spiritualistic to psychology lent popular scientific credibility to a Progressive ideology and foreshadowed psychology's shift in the 1920s towards a greater emphasis on the environment and interest in the unconscious. PMID- 1891539 TI - Circadian aspects of epileptic behavior in comparative psychophysiology. AB - This paper is concerned with some experimental and clinical problems regarding the circadian chronobiology of epilepsy. Rhythmometrically analyzed, the temporal fluctuations of seizure susceptibility tend to indicate that epileptic events are circadian stage-dependent processes whose chronobiologic characteristics are possibly predictable on the basis of mathematical models. As an integrative discipline in physiology and psychology, behavioral chronobiology renders possible the discovery of new regulation processes concerning the central mechanisms of epilepsy. In this respect, the circadian psychophysiological patterns of epilepsy express dynamical biological systems which suggest some intermodulating endogenous processes between vigilance level and seizure susceptibility. Moreover, such chronobiologic studies applied to epileptic behavior suggest the development of new heuristic aspects in the field of comparative psychophysiology. PMID- 1891540 TI - Relationship of religiosity to wellness and other health-related behaviors and outcomes. AB - The relationship of religiosity to health-enhancing attitudes and behaviors (wellness), health-compromising behaviors, and adverse health-related outcomes was examined in a sample of 1,077 college students from a large, comprehensive mid-western university. In general, religiosity was positively correlated with wellness and inversely correlated with health-compromising behaviors and illnesses. Interpretation of the findings was complicated in some instances by significant interactions between study variables. PMID- 1891541 TI - Temporal consistency of the WAIS-R Memory/Freedom from Distractibility factor in a nonclinical sample. AB - The temporal consistency of the WAIS-R Memory/Freedom from Distractibility factor and its intrafactorial components were measured over a 4-wk. period in a nonclinical sample of 22 undergraduates. A modest but significant consistency coefficient of .49 was obtained for Memory/Freedom from Distractibility. Neither intrafactorial component manifested significant temporal consistency over four weeks. Significant retest improvements were expected and observed on Memory/Freedom from Distractibility and Advanced Computation. These retest improvements were interpreted in terms of task familiarity rather than specific content recall. The reported temporal consistency coefficients appear to represent the lowest consistency for these neuropsychological constructs. The routine use of Memory/Freedom from Distractibility was questioned pending more comprehensive measurement of reliability. PMID- 1891542 TI - Preoperative anxiety and motives for surgery. AB - Preoperative anxiety was assessed in 20 patients undergoing surgery for esthetic reasons and 20 other surgical patients. Patients with plastic surgery reported significantly less anxiety than patients with general surgery, as measured by the State-Trait Anxiety Inventory. PMID- 1891543 TI - Relationship between self-image and depression in adolescents. AB - The study investigated the relationship between self-concept and depression among 202 adolescents using a multidimensional measure of self-concept, the Offer Self image Questionnaire, and the Children's Depression Scale. Correlations were significant and low to moderate (range from .24 to .67) for both 63 boys and 139 girls. PMID- 1891544 TI - Medications and information for patients: a quick look. AB - A replication of a report of patients' failure to ask about medications and desire to know by the National Council on Patient Information and Education showed 97% of 779 students responded that they do ask questions about prescribed medications but also would like more information. Findings are discussed in terms of methodological considerations. PMID- 1891545 TI - Death anxiety among Lebanese samples. AB - An Arabic version of the Templer Death Anxiety Scale was administered to 673 Lebanese volunteer subjects (164 boys, 165 girls in secondary school, 170 men, 174 women undergraduates). Females attained higher mean death anxiety scores than males. The Lebanese samples had either the same or a lower mean score on death anxiety than their Arab peers, that is, Egyptians and Kuwaitians and also US samples. Split-half reliabilities ranged from .57 to .68. PMID- 1891546 TI - Attempted suicide and the lunar cycle. AB - An analysis of 383 cases of attempted suicide presented to the Accident and Emergency Department during 12 complete lunar cycles (one year) gave no support for an association between attempted suicide and the lunar cycle, especially the full moon. No control for weekends or holidays was made. PMID- 1891547 TI - Regional correlations between suicide and homicide rates for 1986. AB - In reporting the suicide rate and the homicide rate for 1986, the Bureau of the Census divided the United States into nine divisions. This note reports the Pearson correlation between the suicide rate and homicide rate for the states in each division for 1986. Except for the East South Central division, the correlation between the suicide rate and the homicide rate for each division for 1986 was not significant. PMID- 1891548 TI - Demographic predictors of self-reported loneliness in adults. AB - The relative magnitude of individual demographic characteristics, compared with other demographic characteristics, in the prediction or explanation of frequency of loneliness has not been examined or reported in the literature. The relative strengths of a series of demographic variables (gender, age, marital status, household income, educational attainment, race or ethnicity, employment status, and occupation) in explaining frequency of loneliness in a random sample of 8,634 adults residing in a large metropolitan county were examined. Logistic regression analysis indicated several variables significantly affected group membership as lonely vs not lonely: marital status, household income, gender, and educational attainment. The strongest predictor of all was marital status. Age group as a predictor variable approached significance, but employment status, occupational, and race/ethnicity were not significant predictors of group membership as lonely vs not lonely in the logistic regression model. PMID- 1891549 TI - Teenage gambling: a pilot study. AB - Structured interviews were conducted of 40 gamblers between 17 and 24 years of age. They were males who reported playing 3 or more times per week and spending 1 pound to 4 pound per session. Many were unemployed or at school. PMID- 1891550 TI - Relationship between burnout and performance. AB - This paper seeks to clarify the nature of the relationship between burnout and both perceived and actual performance. A sample was chosen for whom a clear and objective measure of actual performance was available. This was a group of 95 mid career MBA students, for whom examination scores were obtained. A questionnaire containing items assessing burnout and perceived performance was administered. There were significant positive correlations between the measure of burnout and the items assessing perceived performance, particularly those reflecting self esteem. There was no significant association between the measure of burnout and actual performance. It is suggested that (i) a clear distinction between actual and perceived performance be made in the burnout literature; (ii) it is premature to assume burnout will lead to an actual decline in performance; (iii) the notion of deteriorating perceived performance in relation to burnout may have more to do with general feelings of self-esteem than performance or accomplishment per se. PMID- 1891551 TI - Gender differences in categorizing adolescents' weight status. AB - Categorization of normal or overweight status, using percent overweight and visual inspection, showed good agreement for 51 adolescent girls, but not 70 boys. Only 49% of boys with high relative weights were seen as overweight compared to 90% of girls. PMID- 1891552 TI - Performance of residents in anesthesiology as related to measures of personality and interests. AB - 79 male and 16 female residents in anesthesiology at six training centers took the California Psychological Inventory (CPI) and Strong Interest Inventory (SII) in Year 1 and were rated for performance two years later. Descriptively, the total sample scored highest on CPI scales for Dominance, Social Presence, and Achievement via Independence, and on SII scales for investigative, mathematical, and medical science interests. Scores from a four-scale CPI cluster of Empathy. Socialization, Achievement via Conformance, and Achievement via Independence correlated .39 with ratings for men and .31 with ratings for women. In another sample of 20 residents, the cluster score correlated .30 with ratings gathered three years after testing. These findings, consonant with prior research, suggest that attributes such as empathy, strong internalization of pronormative values, and the ability to work well within either structured or open settings are conducive to superior performance in the specialty. PMID- 1891553 TI - Educators' appraisal of their stressors and coping strategies. AB - An assessment of 188 educators' perceptions of their appraisal of stress producers and coping mechanisms on McWilliams and Schnorr's questionnaire were studied. Subjects identified their stress as mild, moderate, and severe. Analysis of scores identified educators' stressors and coping strategies and showed significant differences among the three stress-level groups on statements about 12 stress producers and 8 coping mechanisms. PMID- 1891554 TI - A two-factor measure of jealous responses. AB - A two-factor measure of jealous reactions was created, based on previously proposed theories. The first scale measures the extent to which one reacts in partner-enhancing ways when faced with a jealously-evoking situation, and the second scale measures the extent to which one reacts in partner-attacking ways when faced with such situations. A validation study supports the construct validity of the scales. PMID- 1891555 TI - Physical and mental health changes in retirement age. AB - Effects of retirement on health were studied in a prospective follow-up study (TURVA project). The subjects were examined when they were 62 and 66 years old. At the beginning of the study more than half of the subjects were still working and the rest of them pensioned. Retirement had no clear effect on the subjects' physical health. Mental health of the subjects who retired at age of old-age retirement became better than that of the subjects who retired before the study. Diminished work stress may explain positive changes in mental health during retirement process. PMID- 1891556 TI - Daily stressors and systemic lupus erythematosus: a longitudinal analysis--first findings. AB - Patients with systemic lupus erythematosus (SLE) and a comparison group of patients with rheumatoid arthritis (RA) completed the Dutch Everyday Problem Checklist and the Dutch Arthritis Impact Measurement Scale measuring physical and psychosocial aspects of illness. Both scales were completed 9 times at 6-week intervals. In addition several hematological and serological parameters were assayed. Analysis over several time points resulted in only weak correlations between the variables under study. The most remarkable finding of this study was that in SLE patients number and intensity of daily stressors are more strongly related to physical and psychosocial status than in RA patients. PMID- 1891558 TI - Cognitive and emotional disturbances in systemic lupus erythematosus. AB - Do patients with central nervous system systemic lupus erythematosus (CNS-SLE) demonstrate more cognitive and emotional disturbances than SLE patients without cerebral involvement (non-CNS-SLE) and patients with rheumatoid arthritis (RA)? Test results indicated that CNS-SLE patients performed less well on two concentration subtests in comparison with both non-CNS-SLE and RA patients and scored higher on three psychopathology scales (borderline personality symptoms, dysthymic symptoms and psychotic depression). The representativity and reliability of the present results will be discussed. PMID- 1891557 TI - Differential diagnosis of hypochondriacal fears and beliefs. AB - Any undue concern with bodily function is often labeled as hypochondriacal. Kellner's Illness Attitude Scales, self-rating instruments, distinguish between generic worry about illness, concern about pain, health habits, hypochondriacal beliefs, thanatophobia, disease phobia, and bodily preoccupations. The Illness Attitude Scales have been used in a number of studies concerned with patients suffering from DSM-III-R hypochondriasis, panic disorder, melancholia, in the medically ill, in pregnant women, during medical procedures such as mammography, and in experiments in therapeutics, such as drug trials. The results of these studies and of clinical investigations suggest that the differential diagnosis between hypochondriacal beliefs (characterized by resistance to reassurance), disease phobia, thanatophobia, and the other less specific illness attitudes, is worthy of clinical attention and may entail prognostic and therapeutic implications. Pilowsky's concept of abnormal illness behavior, unlike the DSM-III R, provides a framework for such differentiation. PMID- 1891559 TI - Psychiatric symptoms as features of systemic lupus erythematosus. AB - An enquiry of the Dutch Lupus Patients Society revealed that 49% of the members had experienced psychiatric symptoms before systemic lupus erythematosus (SLE) was diagnosed and 33% had sought professional psychiatric help at that stage. To determine the frequency of SLE on psychiatric admission 2,121 patients were tested for the presence of SLE-specific antinuclear and anti-DNA autoantibodies. The results suggest that SLE is a cause of admission in psychiatric hospitals at the rate of 0.1-0.2% and routine screening of antinuclear and anti-DNA antibodies on admission is not an effective diagnostic approach. PMID- 1891560 TI - Denial in heart transplant candidates. AB - The concept of denial is important for the psychosomatic understanding of cardiovascular disease and treatment. This study evaluated denial using several psychometric assessment scales in patients referred for psychiatric evaluations prior to heart transplantation. Surviving patients who had a mean survival of more than 38 months had less denial than nonsurviving patients who had a mean survival of 4 months. These findings are very preliminary, but interesting, and would encourage further investigation of denial in these patients. Denial is a complex psychological variable, only part of which may be applicable to surgery patients. PMID- 1891561 TI - The proportion of patients with cognitive impairment after coronary artery bypass surgery: an 8-month follow-up study. AB - The aim of this study was to investigate cognitive function after coronary artery bypass surgery and the association of this with surgical variables. All male patients scheduled for elective surgery, aged 40-64 years, mean age 54 +/- 6 (n = 104), and participating in a randomized rehabilitation study, were included. A comprehensive psychodiagnostic examination was conducted preoperatively, 2, and 8 months postoperatively. The assessment of change was conducted using tertiles, defined according to population norms. More patients revealed improvement than impairment, and practically no significant associations with surgical variables were found. PMID- 1891562 TI - Coping strategies and course of disease of breast cancer patients. Results of a 3 year longitudinal study. AB - In a prospective 3-year longitudinal study investigating correlations between coping strategies and course of breast cancer a consecutive series of 107 patients were assessed for biological and psychosocial data. Data analysis indicated no significant correlations between coping strategies and course of cancer. On the other hand, biological parameters such as size of tumor and lymph node stage at time of surgery correlated significantly with the course of disease. It was concluded that the assessed indicators of coping are of little importance in regard to the course of the disease and less predictive compared with somatical parameters of breast cancer. PMID- 1891563 TI - Patients' illness models in chronic pelvic pain. AB - A modification of Kleinman's approach to eliciting concepts that patients have about their illnesses was applied to 64 patients with chronic pelvic pain. The women involved did not have clear schemata about causes of the process, and displayed flexibility in the concepts they did have. A significant proportion had clear ideas about what they did not want in terms of treatment. Worries focussed on interminability and effects on sex and work. It appears that offering a simple explanatory model such as that based on venous congestion fulfils some of the treatment needs in this group. Kleinman's approach could be more widely employed. PMID- 1891564 TI - Diabetologists' assessments of their outpatients' emotional state and health beliefs: accuracy and possible sources of bias. AB - The accuracy of physicians' perceptions of their patients' emotional state and health attitudes was examined in a diabetes outpatient clinic by comparing patients' ratings of anxiety, depression and health locus of control with physicians' ratings. In 234 patients, doctors' and patients' ratings correlated significantly for depression and anxiety. The physicians rated patients with a strong belief in control of health by others as most dependent on doctors. Men but not women with external locus of control were also rated as very dependent on doctors. Anxious or depressed patients were rated by their doctors as less able to cope with diabetes. The results indicate that non-psychiatric physicians are able to assess their patients' emotions and health attitudes with greater accuracy than is usually assumed. PMID- 1891565 TI - Glycaemic control in adolescents with type I diabetes and parental expressed emotion. AB - The parents of 34 adolescents with type I diabetes were interviewed using the Camberwell Family Interview, a well validated and reliable standardised interview which measures aspects of family interaction previously reported as important in the families of diabetics. Contrary to predictions from previous research, poor glycaemic control was not associated with parental apathy, criticism of the child with diabetes, or marital discord. Greater emotional involvement by parents was associated with good glycaemic control. Overall, there was close agreement between parents in their responses although mothers showed more accurate appraisal of their child's diabetes than did fathers. PMID- 1891567 TI - White collar stress: what studies of physicians can teach us. AB - The impact of occupational stress on physicians and their medical practice has been subject to much debate but relatively little research. This paper reviews some recent studies concerning the psychosocial work environment of physicians. Psychiatric and cardiovascular epidemiologic data indicate that physicians are at similar or enhanced risk to socioeconomically comparative groups. Clinical studies of physicians reveal associations between psychosocial work characteristics and traditional cardiovascular risk factors. Further work is needed to enhance our understanding of the implication of present work environments on the health and well-being of physicians as well as other health care workers. PMID- 1891566 TI - Psychosocial stress as a risk for breast cancer. AB - Life events, important emotional losses, difficult life situations, and psychological characteristics were investigated in a case-control study of 87 breast cancer patients and their controls. In a second part, the effect of stressful life events preceding cancer diagnosis on survival was studied in an 8 year follow-up of the breast cancer group. The control group was selected from the general female population and matched for sex, age, number of child-births, and language. The findings showed that breast cancer patients had significantly more life events, important losses, and difficult life situations prior to the discovery of the breast tumor than controls. The analysis indicated that important losses during a 6-year prodromal period and life event scores prior to examination on both the 12-month and modified 6-year Social Readjustment Rating Scale were associated with subsequent development of breast cancer. The association persisted after adjustment for marital status, education, and social class. The findings of the survival analyses indicated that life events in the 12 months preceding the onset of breast cancer and lower social class were associated with a smaller chance of disease-free and overall survival after controlling for clinical factors. PMID- 1891568 TI - Prevention of psychopathology with early interventions. AB - Early interventions aiming at prevention from future psychopathology are critically evaluated. These interventions include: genetic psychiatric counselling, family planning, improvement of the physical health of the population, prenatal care, intervention in childhood, improvement of the physical health of the child, improvement of the home environment and improvement of the school environment. Although concrete evidence about the effectiveness of many of the above methods is lacking, they are nevertheless worth applying because on an individual basis they often contribute to the alleviation of human suffering. It is pointed out that early preventive interventions are particularly indicated in predisposed individuals (e.g. persons with hereditary predisposition for schizophrenia who must be protected from perinatal complications in order to be prevented from future development of this illness) or high-risk groups (e.g. the siblings of 'battered' children who have a greater probability of being abused by their parents, or 'battered' children who, when becoming parents, have a raised probability of abusing their own children). PMID- 1891569 TI - Consultation-liaison psychiatry 1990. AB - Consultation-liaison (C-L) psychiatry is a subspecialty concerned with clinical service, teaching, and research by psychiatrists in nonpsychiatric health care settings. These activities are focused on the physically ill and on the somatizing patients. The main objective of C-L psychiatry is to maintain a bridge between psychiatry and medicine for the sake of providing biopsychosocial health care. C-L psychiatry's functions include clinical work, teaching, and research at the interface of psychiatry and medicine. This field has grown substantially in the past two decades as is brought out in this article. PMID- 1891570 TI - Psychoneuroendocrinology of stress and emotions: issues for future research. AB - It is stated that much psychoneuroendocrinological research is carried out that lacks a theoretical framework and therefore adds little to our current knowledge. Therefore, five research issues have been presented which need further exploration: (1) the temporal relation between subjective and biological stress responses; (2) the question of the psychobiological specificity; (3) the relationship between endocrine responses to acute and to chronic stressors; (4) the relationship between endocrine activity and susceptibility to disease, and (5) the mediating and moderating effects of personal factors (coping, personality, and task performance) on psychobiological responses. It is argued that the study of these issues will increase our understanding of the stress phenomenon. PMID- 1891572 TI - Psychosocial cardiovascular risks--on the double loads in women. AB - The author discusses gender differences in the psychosocial correlates of cardiovascular risk. A moderate amount of overtime work was associated with a decreased risk of myocardial infarction in men but a corresponding increased risk in women. The reason for this difference may be the double role (home and paid work) of women. Emotional states in diaries differed between men and women in the same occupations, and these differences seemed to some extent to be occupation specific. PMID- 1891571 TI - Neuroendocrine and immunologic effects of unemployment and job insecurity. AB - We prospectively followed a cohort of 354 blue-collar men and women, some of whom lost their jobs. Results show marked effects during the anticipatory and early unemployment phase on mental well-being, serum cortisol, prolactin, total cholesterol, HDL cholesterol, and phytohemagglutinin reactivity of lymphocytes. Most of these changes appear to be of short-term duration. However, changes in cardiovascular risk factors are observed at least 2 years following the loss of one's job. Coping style appears to be a major determinant whether or not and how people will react to unemployment. PMID- 1891573 TI - Job stressors and coping in health professions. AB - In spite of their knowledge about stressors, health hazards and coping, health professionals are in general not aware of their own health risks. In an attempt to clarify the issue results of our own studies are compared to the relevant literature. A survey on 1,248 Swiss nurses confirmed the major stressors known: ethical conflicts about appropriate patient care, team conflicts, role ambiguity, workload and organizational deficits. In doctors workload and shortage of time, combined with specific responsibility in decision making, are most prominent. Nevertheless, job satisfaction is still high in both professions. Health hazards in doctors are considerable, although life expectancy has improved and is comparable to the general public, but still lower as compared to other professionals. Depression and substance abuse are related to higher suicide rates. The specific role strain of female doctors is responsible for health risks with an alarming 10 years lower life expectancy than in the general population. Little is known about specific health hazards in nurses, except for burnout. A lack of coping research in the field makes conclusions difficult. Our own studies show limited coping skills in nurses, but good buffering effect in 1,700 Swiss dentists. PMID- 1891574 TI - Can we really teach psychosomatic medicine? A review of successes and failures. AB - Medicine, it seems, is lately in a state of perpetual crisis. Some would attribute the problem, at least in part, to the enduring heritage of Descartes, who imprinted dualistic notions of a separation of mind and body upon medical education and practice. The perspective of psychosomatic medicine has long been hailed as the remedy for flaws in the way medicine has been taught and practiced for at least five decades. If medicine as a humanistic endeavor is to take account of the whole individual, it must encompass biological, social and psychological dimensions of the person. Many attempts at curriculum reform and postgraduate education have had variable success in countering the dualism of medicine. This presentation will discuss the challenge, the problems and the future of psychosomatic teaching, with illustrations from a variety of educational experiments. PMID- 1891575 TI - Psychodynamic, time-limited group therapy in rheumatic disease--a controlled study with special reference to alexithymia. AB - Forty-six female patients with rheumatoid arthritis or primary Sjogren's syndrome participated in a prospective, controlled study of psychodynamic, time-limited group therapy. The paper concentrates on the qualitative outcome evaluated according to the patients' perceptions of what was appreciated as being most helpful in the group. Yalom's 'curative factors Q-sort' served as parameter of effect. Special attention will be given to the prevalence of alexithymia in rheumatic patients, and to the possibilities of ameliorating alexithymic features through group therapy. PMID- 1891577 TI - The body ego from the point of view of psychophysical fusion. AB - Freud introduced the concept of body ego as a basis for all later ego development. He did not describe it in detail, however, and the nature of the body ego has remained unclear. I suggest that the original body ego in the infant is the outcome of psychophysical fusion, i.e. fusion of experienced pleasure with sense impressions coming from without (the mother). The result of this leads to the establishment of primal repression and the psychosomatic boundary. The experiences of fusion are gradually internalized to form a stable ego nucleus. It is further suggested that the remarkable hypnagogic and dream phenomena described by Isakower and Lewin reflect the internalized result of this process and offer a chance to investigate these early and developmentally central phenomena. PMID- 1891576 TI - Psychotherapy in patients with poorly controlled type 1 (insulin-dependent) diabetes. AB - We studied a group of 9 poorly controlled type 1 diabetic patients who were referred to the metabolic ward for a 10-day intensive patient education and treatment period and followed thereafter for 1 year. The psychodynamically and phase-specifically oriented intensive psychotherapy was prescribed. In terms of mental coping ability assessed by an index constituting the attitude towards diabetes, the family support and the expectations from the psychotherapy, the final outcome was classified as good or moderate in 7 of 9 patients. The complexities of different personality characteristics and their interaction with metabolic control are issues that require further exploration. PMID- 1891578 TI - Guidelines for the family therapeutic approach to eating disorders. AB - After a brief historical overview of the literature on family therapy in eating disorders, the authors' own clinical experience is summarized in some practical guidelines: give the family therapist a central position within the team, engage the family and/or spouse as co-therapist, explore the message of the eating disorder on different levels, neutralize the symptoms outside of the family interaction, promote direct communication, facilitate the separation individuation process, and be available for a long time. Finally some special issues are discussed: sexual and/or physical abuse in the family, broken-home situations and single-parent families, married and chronic patients. PMID- 1891579 TI - The prevalence of bulimia nervosa in a Hungarian college and secondary school population. AB - A two-stage survey was conducted to determine the prevalence of bulimia and bulimic behavior in 2 Hungarian nonclinical samples. In the college sample 1.3% of females and 0.8% of males met DSM-III-R diagnostic criteria for bulimia nervosa. In the adolescent sample no bulimic subjects were found, weight control behaviors are infrequent, but the attitudinal antecedents of bulimia are present in females. PMID- 1891580 TI - Prognostic factors in outpatient psychotherapy of bulimia. AB - Little is known about prognostic factors in the treatment of bulimic patients. In the context of an ongoing study we looked at 1-year symptomatic outcome of 37 outpatients fulfilling DSM-III-R criteria for bulimia nervosa in relation to a variety of measures at first assessment. These included multiple measures of depression, measures of borderline personality disorder, a personality inventory, a symptom checklist and information about the history and the severity of the illness. Results add evidence to the importance of personality variables in predicting outcome: patients with high scores on the Borderline Syndrome Index indicating a severe disturbance tend to have poorer symptomatic outcome, especially when they also experience themselves as dominant (Giessen-Test). Other factors, including abuse of alcohol and history of anorexia did not allow prediction of outcome. PMID- 1891581 TI - Psychosomatic nursing assessment of psychiatric patients. AB - This article presents the results of a research study on 547 mental patients testing a form of nursing assessment of mental patients in psychiatric and in general hospitals, as a means to assess their nursing needs and as a basis for planning, implementation and evaluation of their personalized holistic nursing care. The study showed that more depressive than schizophrenic patients went to the general hospital for help. The reverse was observed in the psychiatric hospital. The psychological nursing needs of the patients were significantly correlated with their somatic nursing needs. The psychological as well as the somatic nursing needs of the patients were significantly correlated with sex, age, somatic health state and mental health state in general, and not with their concrete psychiatric diagnosis. It is concluded that the psychiatric nursing assessment should be oriented towards the investigation of the patient's psychosomatic nursing needs rather than be based on his medical diagnosis. PMID- 1891582 TI - Therapy outcome of two treatment models for bulimia nervosa: preliminary results of a controlled study. AB - Beyond the reduction of the core symptoms, different modification patterns are expected due to differing emphases in two alternative types of treatment for bulimia nervosa: inpatient analytic and outpatient systemic therapy. The initial results of a study with a waiting-list control group are reported. Eating disorders of the bulimic women definitely improved in both therapy groups, the results for the inpatient group (n = 27) indicate a basic change in the attitude towards eating. PMID- 1891583 TI - Everyday addictive behavior of bulimic women. AB - The comorbidity of bulimia nervosa and other forms of drug use or dependence is frequently reported, but statistical comparison as well as reference to a theoretical background is rare to be found. In order to assess the associated dependencies of bulimia, 105 bulimic women participated in a structured interview with a focus on their everyday drug use. Our results suggest that there is little evidence of other forms of related addicting drugs among bulimics. A possible theoretical background which explains the resulting pattern of their taking of stimulants and drugs is the common belief about desired effects of the consumption of these substances. PMID- 1891584 TI - Psychosomatic symptoms in preadolescent children. AB - As part of a Finnish national epidemiological study on child psychiatric disorders, psychosomatic symptoms were studied in a sample (n = 1,100) of 8-year old children on the basis of self-report questionnaires by the children, their parents and teachers. Psychosomatic symptoms were common, although constant symptoms were rare. There were no sex differences in the occurrence of symptoms, but interesting differences were observed in associations between symptoms and other factors. Psychosomatic symptoms were strongly associated with depression scores and school performance. PMID- 1891586 TI - Prevalence of psychosomatic symptoms in children. AB - Somatic symptoms reflecting psychic components were recorded in connection with the Finnish National Epidemiological Study of Psychiatric Disorders. In the present work, according to the parents' concerns, frequent headache was found in 2.8%, recurrent abdominal pain in 2.4%, asthma in 0.7%, enuresis in 1.5% and soiling in 0.3% of the children. Children complaining frequently of different pains were reported in 1.0% by the teachers. Distribution by sex, population density areas and family structure are also given. PMID- 1891585 TI - Psychosomatic interaction between mother and infant during breast feeding. AB - Within the context of a major research project on the impact of mother's depression on breast feeding, this study presents a qualitative analysis of mother-infant interaction during a single breast feeding situation. From the holistic perspective there emerged five central themes of interaction, which all displayed a different purpose. Mothers had quite often difficulties in psychosomatic interaction during a phase of hungry eating. More detailed analysis revealed some interesting differences between the depressed and nondepressed mothers. PMID- 1891588 TI - Transitional object and children with chronic disease. Comparative study of the forms of transitional object among children with diabetes mellitus or rheumatic disease. AB - The prevalence of the transitional object among children with rheumatic disease and diabetes mellitus is examined in this comparative study with highly matched groups. There is no evidence which could indicate the lack of transitional objects among these children. In the rheumatic group the transitional object was more common than in the other groups and the children used it later than others. The soothing function of transitional object is discussed. PMID- 1891587 TI - Psychosomatic symptoms in adolescent twins. Longitudinal twin study with special reference to psychosomatic symptoms. AB - In a cohort study of 234 twin pairs followed from pregnancy to 12-20 years of age the psychosomatic symptoms of adolescents were inquired from their parents. Girls had symptoms more often than boys. Intrapair concordances were high. The mothers' favorite children had psychosomatic complaints more often than the father's favorites or those who were equally close to each parent. Psychosomatic complaints were more frequent in the submissive members of twin pairs and nervous symptoms in the dominant ones. PMID- 1891589 TI - Interrater agreement when assessing alexithymia using the Drawing Completion Test (Wartegg Zeichentest). AB - Due to insufficient agreement regarding the definition of the concept of alexithymia, a number of theoretically different approaches have been used when assessing the phenomenon. Primarily psychiatric interviews and questionnaires have been used, but also projective tests, principally the TAT, and the Rorschach. In this study four independent assessments of alexithymia were made, using the Wartegg, for a cohort of 50 randomly selected subjects, acting upon the alexithymia description of von Rad. Intraclass correlations were on an average 0.77. PMID- 1891590 TI - Play and energy regulation in mammals. AB - Analysis of ecological constraints on juvenile mammals suggests that energy expended in play behavior does not reduce fitness, but actually increases it. When viewed as a promoter of adaptive energy loss, play can be considered an antipredator strategy. In addition, it may balance a low-protein diet in favor of growth, as well as increase resistance to pathogens and to cold exposure. These short-term benefits result from activation of the sympathetic nervous system (SNS), which is hypothesized to occur during play. SNS activation increases heat production in brown adipose tissue. The energy-regulation approach generates many predictions that are supported in the literature, and others that can be empirically tested. PMID- 1891591 TI - Environmental sex determination in reptiles: ecology, evolution, and experimental design. AB - Sex-determining mechanisms in reptiles can be divided into two convenient classifications: genotypic (GSD) and environmental (ESD). While a number of types of GSD have been identified in a wide variety of reptilian taxa, the expression of ESD in the form of temperature-dependent sex determination (TSD) in three of the five major reptilian lineages has drawn considerable attention to this area of research. Increasing interest in sex-determining mechanisms in reptiles has resulted in many data, but much of this information is scattered throughout the literature and consequently difficult to interpret. It is known, however, that distinct sex chromosomes are absent in the tuatara and crocodilians, rare in amphisbaenians (worm lizards) and turtles, and common in lizards and snakes (but less than 20% of all species of living reptiles have been karyotyped). With less than 2 percent of all reptilian species examined, TSD apparently is absent in the tuatara, amphisbaenians and snakes; rare in lizards, frequent in turtles, and ubiquitous in crocodilians. Despite considerable inter- and intraspecific variation in the threshold temperature (temperature producing a 1:1 sex ratio) of gonadal sex determination, this variation cannot confidently be assigned a genetic basis owing to uncontrolled environmental factors or to differences in experimental protocol among studies. Laboratory studies have identified the critical period of development during which gonadal sex determination occurs for at least a dozen species. There are striking similarities in this period among the major taxa with TSD. Examination of TSD in the field indicates that sex ratios of hatchlings are affected by location of the nests, because some nests produce both sexes whereas the majority produce only one sex. Still, more information is needed on how TSD operates under natural conditions in order to fully understand its ecological and conservation implications. TSD may be the ancestral sex-determining condition in reptiles, but this result remains tentative. Physiological investigations of TSD have clarified the roles of steroid hormones, various enzymes, and H-Y antigen in sexual differentiation, whereas molecular studies have identified several plausible candidates for sex determining genes in species with TSD. This area of research promises to elucidate the mechanism of TSD in reptiles and will have obvious implications for understanding the basis of sex determination in other vertebrates. Experimental and comparative investigations of the potential adaptive significance of TSD appear equally promising, although much work remains to be performed. The distribution of TSD within and among the major reptilian lineages may be related to the life span of individuals of a species and to the biogeography of these species.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1891592 TI - Synthesis of life in the lab? Defining a protoliving system. AB - The synthesis of a living system in the lab has been judged by a number of critics as partly attained by the proteinoid microsphere because of its primitive properties of metabolism, growth, and reproduction. These same critics, however, judge the organism as not alive, or as being 50 to 75 percent alive (Baltscheffsky and Jurka, 1984), owing to the absence of a nucleic acid genetic coding mechanism. The experiments in retracing evolution suggest, however, that the self-sequencing of amino acids was the evolutionary precursor of modern nucleic acid templating; the genetic memory is the molecule. The proteinoid microsphere is not a modern living system, but does represent at least a protoliving system (Fox and Dose, 1972). Berra (1990, p. 75) has commented on other difficulties in defining a protoliving system. In Berra's opinion, metabolism, reproduction, responsiveness to stimuli, and cellularity constitute or describe aliveness. These properties characterize proteinoid microspheres. A number of experiments demonstrate that amino acids in aminoacyl adenylates yield specific products, whereas nucleotides are without effect. For this and related reasons, especially the demonstrated self-sequencing of amino acids when they are warmed, resultant bio-functional properties of self-assembled microstructures, and demonstrated self-sequencing of amino acids in modern systems, the results appear to bridge from the chemical era to the biological period. All the above emerges from a departure in style of research (Young, 1984; Pauling and Zuckerkandl, 1972). The latter authors said, "It appears likely that biogenesis is the passage from a 'non-living system' existing in a large number of states to a 'living' system also existing in a large number of states."(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1891593 TI - The amalgam controversy. PMID- 1891594 TI - The safety of dental amalgam: the classic problem of early questions and premature conclusions. PMID- 1891595 TI - The amalgam controversy. PMID- 1891596 TI - Response to patients who inquire about the safety of dental amalgam. PMID- 1891597 TI - The hazards of gloves in dentistry. PMID- 1891598 TI - The all-porcelain, resin-bonded bridge. AB - This case report describes the clinical and laboratory procedures for the fabrication and insertion of In-Ceram all-porcelain, resin-bonded bridges. All porcelain crowns and fixed partial dentures have better biocompatibility and better esthetic results than do ceramometal restorations. In-Ceram has been shown to have better physical properties than other ceramic or glass materials. However, long-term clinical studies of the material are not yet available. PMID- 1891599 TI - The importance of a coordinated restorative and maintenance program following periodontal therapy: a case report. AB - The problems arising during the maintenance phase of therapy following a combination of periodontal, orthodontic, and restorative treatment are illustrated by this case report. Emphasis is placed on the combined responsibility of the patient, general dental practitioner, and periodontist to recognize signs of recurrent disease at an early stage, thereby allowing corrective measures to be initiated promptly. By applying these principles, even when disease recurs during the maintenance phase, re-treatment is possible and a satisfactory result can be achieved. PMID- 1891600 TI - Burnished versus nonburnished application of citric acid to human diseased root surfaces: the effect of time and method of application. AB - Citric acid (pH = 1) was applied passively or by vigorous burnishing for 3 or 5 minutes to diseased human root surfaces following root planning in vitro. Control surfaces were similarly treated with saline only. Teeth were fixed in glutaraldehyde, dehydrated, freeze-dried, and sputter coated with gold for scanning electron microscopic viewing. Results suggested that optimal exposure of collagen and demineralization occurred with the burnishing application of citric acid for 3 minutes. Although somewhat similar results were found with passive application for 5 minutes, the result of the burnishing application for 5 minutes was that the root was overdemineralized or that the exposed collagen was completely obscured by an amorphous layer that was suggestive of protein denaturization. PMID- 1891601 TI - A method for bonding to tooth structure using phosphoric acid as a dentin-enamel conditioner. AB - In clinical practice it is difficult to keep acid etchants off the dentinal surface during bonding procedures. If the acid etchant could be used as part of the overall conditioning system, technique sensitivity would be reduced. This paper reports the data obtained with the use of phosphoric acid as a dentin enamel conditioner in a bonding system developed by the author. In vitro bond strength and microleakage were examined using Dual Cure Scotchbond as a control. In both tests, the experimental group showed statistically significantly better results than did the control. A clinical study of 140 Class II restorations showed no postoperative sensitivity, and all teeth were vital after 18 months. PMID- 1891602 TI - Porcelain laminate veneer provisionalization using visible light-curing acrylic resin. AB - Placement of porcelain laminate veneers has become a relatively common procedure. Occasionally it is necessary to fabricate provisional restorations. For these situations, the use of self-curing acrylic resin and composite resin has been described in the literature. Extensive trimming and finishing procedures are often necessary, and, because of the inherent fragility of the materials, the provisional restorations are prone to breakage. To improve the technique, visible light-curing acrylic resin can be used to fabricate direct provisional restorations. The material is available in several shades, has excellent manipulative properties, and does not necessarily require a custom matrix, offering significant advantages over a composite resin or self-curing acrylic resin. PMID- 1891603 TI - The effect of bonding agent and fissure sealant on microleakage of composite resin restorations. AB - The purpose of this study was to assess, in vitro, the microleakage of Class V composite resin restorations following sealing of the margins with a fissure sealant or the resin component of a dentinal bonding agent, and to compare it to the microleakage of an unsealed control group. All groups of teeth showed some degree of leakage at the gingival margin. Statistical analysis showed that there was significantly less leakage when the fissure sealant (P less than .01) and bonding agent (P less than .001) were used than there was in the control group, in which the margins had not been sealed. There was no statistically significant difference between the two experimental groups. There was no leakage at the enamel margin in any of the teeth. PMID- 1891604 TI - Fluoride-releasing removable appliances. AB - A method was developed to give removable appliances a fluoride-releasing capability. Visible light-cured glass-ionomer cement inserts were made, placed in resins commonly used for removable appliances, and evaluated for fluoride release over a 2-month period. Fluoride release was measured daily for 7 days, weekly for 4 weeks, and monthly for 1 month. All specimens released fluoride at every time period. There was a "burst effect" in which more fluoride was released the first day, but the amount released decreased significantly on the second day. The amount of fluoride released decreased at each of the daily and weekly measurements, but became relatively stable after 7 days. All specimens were still releasing fluoride at the end of the 2-month test period. PMID- 1891605 TI - Scanning electron microscopic and energy dispersive x-ray evaluation of two smear layer-mediated dentinal bonding agents. AB - Teeth treated with smear layer-mediated dentinal bonding agents and restored with composite resin were examined at the dentin-restoration interface by means of scanning electron microscopy used in conjunction with energy dispersive x-ray analysis. Results indicated that these dentinal bonding agents actually bonded to the smear layer, and samples demonstrated delamination of the smear layer from underlying dentin following thermocycling. This finding suggests that the stresses developed within the composite resin exceeded the adhesive strength of the smear layer to dentin. Thus, the bond strength for dentinal bonding agents that require the presence of the smear layer cannot exceed the adhesion of the smear layer to dentin. PMID- 1891606 TI - Psychophysical measurement on pain perception after administration of a topical anesthetic. AB - Topical anesthetics are routinely used to reduce the discomfort that patients perceive during dental injections. The purpose of this investigation was to correlate the expectancy of pain and the effect of pretreatment instructions with the severity of pain perceived upon topical anesthetic use and dental injection. The treatment, topical placebo versus topical anesthetic, was administered in a double-blind manner. Following testing for expectations, the administration of instructions, and placement of the topical, the injection was given. The patients were then asked to rate their injection experience on a posttreatment questionnaire. The results of this investigation reinforce the importance of psychological variables in the mediation of pain perceived during dental procedures. PMID- 1891607 TI - The effect of neuromuscular diseases on the development of dental and occlusal characteristics. AB - Fourteen patients suffering from primary muscular disease (myopathies), including seven with Duchenne's muscular dystrophy, were compared to 11 patients whose neuromuscular disorders were of neuropathic origin. Mesioclusion was observed only in the group with Duchenne's muscular dystrophy. Posterior crossbite, anterior open bite, mouth breathing, and large tongue were also more prevalent in the group with myopathies, especially the Duchenne's patients, than they were in the group with neurogenic disorders. The Duchenne's patients exhibited a statistically significant delay in dental emergence, unlike the patients with other myopathies and those with neurogenic disorders. Dentition and occlusion may be more affected in patients with myopathies, especially Duchenne's muscular dystrophy, than they are in patients with neurogenic disorders. PMID- 1891608 TI - Towards better thrombolytic therapy. PMID- 1891609 TI - Thrombosis, fibrinolysis, and thrombolytic therapy: a perspective. PMID- 1891611 TI - Computer-assisted reinforcement of instruction: effects on adherence in adult atopic asthmatics. AB - A randomized comparison group pretest-posttest experimental design was used to determine computer-assisted instruction effects on adherence to implementing house dust mite avoidance measures in adult atopic asthmatics. Fifty-two subjects were randomly assigned to comparison and experimental groups. The comparison group received traditional instruction in avoidance measures while the experimental group received traditional instruction supplemented by identical information provided by computer-assisted reinforcement of instruction. Adherence was measured by subjects' self-ratings and investigators' observations. Data were collected during two home visits 12 weeks apart. The computer group had significantly (p less than .05) greater adherence scores than the comparison group. The results indicate that computer-assisted reinforcement of instruction is an effective method of increasing self-care behaviors about allergen avoidance activities. PMID- 1891610 TI - Comparison of patient-controlled and nurse-controlled antiemetic therapy in patients receiving chemotherapy. AB - The purpose of this quasi-experimental pilot study was to compare the effect of patient-controlled (PCAE) and nurse administered (NCAE) antiemetic therapy for controlling chemotherapy-induced nausea and vomiting in patients receiving moderate emetogenic chemotherapy. Twenty subjects were randomly assigned to either the PCAE group who received IV antiemetic medication via a patient controlled pump or the NCAE group who received antiemetic medication via nurse administered minibags. Nausea, vomiting, sedation, and drug consumption were measured. There was no difference in nausea scores between the two groups. Subjects in the PCAE group consumed significantly less medication than subjects in the NCAE group. PMID- 1891612 TI - Relationship of resources to emotional distress, somatic complaints, and high risk behaviors in drug recovery and homeless minority women. AB - In a sample of 581 homeless or drug-abusing minority women, the relationship of self-esteem, sense of coherence, and support availability to emotional distress, somatic complaints, and high-risk behavior were investigated. Findings revealed that women who were high in self-esteem and stronger in sense of coherence reported significantly less emotional distress, and significantly fewer high-risk behaviors. In addition, women who were high in any of the three resources reported lower somatic complaints. Regression analyses revealed that coherence, self-esteem and support availability jointly accounted for 49% of the variance in emotional distress, 10% of the variance in high-risk activities, and 26% of the variance in somatic complaints. Implications for empowering women at risk for HIV infection are discussed. PMID- 1891613 TI - The relationship between maternal confidence and mother-infant behaviors in premature infants. AB - The purpose of this study was to investigate the relationship between maternal confidence in mothers of premature infants, maternal behaviors and skills, and infant temperament. The relationship between certain prenatal and background variables and maternal confidence also was assessed. The sample consisted of 49 mother--infant pairs from low socioeconomic backgrounds who were followed for 8 months. Maternal behaviors were assessed in the neonatal intensive care unit and during 4- and 8-month follow-up visits at home. Infant temperament was assessed using the Bates Infant Characteristics Questionnaire. The results revealed that maternal confidence was related to education, income, and parity as well as the presence and severity of intraventricular bleed. There was no relationship between observed maternal behaviors and skills and perceived confidence by mothers. Maternal confidence was related to infant temperament ratings. PMID- 1891614 TI - Content analysis of reminiscences of elderly women. AB - The content of reminiscences of 21 cognitively intact elderly women registered in an adult daycare program was examined. Content analysis of transcripts from a semistructured interview was used to discover categories of reminiscence meaning. The interpretations made about past experiences were grouped under two categories: (a) validating reminiscences that involved confirming or verifying that one had lived a fruitful life; and (b) lamenting reminiscences that involved negative interpretations of past events. Validating themes were: positive self appraisals, choices, social connections, joys, and past to present comparisons. Lamenting themes were: regrets, difficulties, and lacking choice. PMID- 1891615 TI - Patient intensity for nursing index: the measurement model. AB - One part of the psychometric evaluation of the Patient Intensity for Nursing Index (PINI), a new measure of nursing intensity, is reported. The PINI has four interrelated components: (a) severity of illness, (b) dependency, (c) complexity of care, and (d) time. Taken together, the 10 items that make up these four components comprise the multidimensional construct of nursing intensity. Using the factor analytic approach and a model specification search, the measurement model for the Patient Intensity for Nursing Index was identified. The structure consists of Dependency, Severity, and Complexity with time (hours of nursing care) loading on each factor. When results were cross-validated using data from four other hospitals, support emerged for a consistent pattern of factor loadings. The loadings themselves, however, are only partially invariant. Further examination of the relationship between severity and time is suggested and areas for future research are identified. PMID- 1891616 TI - A descriptive analysis of experienced nurses' clinical reasoning during a planning task. AB - A Think Aloud (TA) method was employed to collect verbal data from seven clinical nurses as they reviewed a written case study and formulated a plan of care. Protocol Analysis (PA) of the verbal data resulted in a visual representation of each subject's plan of care and provided information regarding the clinical data that subjects used to plan care. The results demonstrated that frequently problems and interventions were inextricably linked and considered in unison rather than during separate steps of a planning process. This finding has implications relative to the current practice within both nursing education and nursing service of focusing on problems and interventions separately when planning care. PMID- 1891617 TI - The multitrait-multimethod approach to construct validity. AB - The multitrait-multimethod matrix approach as proposed by Campbell and Fiske (1959) was an important contribution to our understanding of the nature of validation procedures. There are, however, problems encountered when using the Campbell and Fiske (1959) approach. The purpose of this article is to discuss the method and selected problems, and to propose an alternate approach to address those problems. PMID- 1891618 TI - Effects of psychological well-being, physical status, and social support on oxygen-dependent COPD patients' level of functioning. AB - Thirty oxygen-dependent patients with chronic obstructive pulmonary disease (COPD) participated in a descriptive correlational study in which investigators examined the relationship between oxygen-dependent COPD patients' psychological well-being, physical status, social support, and level of functioning. Lazarus and Folkman's (1984) theory of psychological stress and coping was used to guide the study. Using multiple regression analysis, physical symptoms had the most predictive power in relation to the level of functioning, accounting for 44.3% of the variance. Among the symptoms, dyspnea had the greatest influence on functioning. PMID- 1891619 TI - Cognitive-perceptual factors associated with antiepileptic medication compliance. AB - The purpose of this study was to determine if selected cognitive-perceptual variables discriminated between individuals who complied with antiepileptic medication therapy and those who did not. Individuals attending an epilepsy clinic and meeting specified criteria were asked to participate. Data from 64 individuals--39 who were classified as compliant and 25 noncompliant--were analyzed using discriminant analysis. The findings revealed that intimacy/assistance, social integration/affirmation of worth, unpredictability, and ambiguity were helpful in discriminating compliant from noncompliant individuals. PMID- 1891620 TI - The use of botanicals for health purposes by members of a prepaid health plan. AB - Interviews were conducted with 100 adults (27 men, 73 women) enrolled in a prepaid medical health plan to investigate their use of botanical remedies. They were asked which of 50 listed herbs they or members of their families had used for health purposes and with what effect; which of 60 listed health problems they had treated with home remedies; and what additional home remedies or alternative health care resources they had used. Over 100 different home remedies were identified, with most considered effective. Individual respondents used from 0 to 33 herbal and plant remedies (Md = 7), some of which have toxic properties. A remedy was reported for almost every health problem listed. Substances most frequently used were aloe vera, honey, peppermint, garlic, eucalyptus, and rose hips; health problems most frequently treated were burns, colds, indigestion, insect bites, insomnia, rashes. Persons who were married, from larger households, of higher socioeconomic status, who had consulted alternative healers, or who had patronized health food stores tended to use home remedies more than their counterparts. Implications for further evaluation of self-care practices are discussed. PMID- 1891621 TI - Relationship of hardiness and current life events to perceived health in rural adults. AB - The purpose of this descriptive study was to examine the relationship of hardiness and current life events to perceived health in rural adults. Instruments used included Kobasa's (1982) Hardiness Scale, SRLE (Holmes & Rahe, 1967), and Engel's (1984) Perceived Health Status. Study results were based on 162 participants responding to a mailed questionnaire. The typical respondent was a 55-year-old married male who lived on a farm or ranch. Participants with higher levels of hardiness demonstrated a better perception of their mental and social health but not physical health. The study findings did not support the buffering effects of hardiness in the presence of greater amounts of stress. PMID- 1891622 TI - The word-graphic rating scale as a measure of children's and adolescents' pain intensity. AB - A program of studies was designed to select and test a pain intensity scale for inclusion in a multidimensional pain assessment tool for children and adolescents. The focus was on determining each scale's validity, reliability, ease of use, preference, and the lack of age, gender, and ethnic biases. Five pain scales were evaluated in four separate studies: a word-graphic rating scale, a visual analogue scale, a graded-graphic rating scale, a magnitude estimation scale (0 to 10), and a color scale. Subjects (N = 1,223) were 8 to 17 years of age and, in three of the studies, were hospitalized and judged to be in pain. In Study 1, well children used the scales to assess pain in an analogue situation selecting the color scale easiest to use and best liked. Convergent validity for the five scales was supported. In Study 2, hospitalized children, who were experiencing pain, overwhelmingly selected the word-graphic rating scale as their choice. A pilot version of a multidimensional pain assessment tool incorporating the word-graphic rating scale was tested in Study 3 using a repeated measures design. The scale demonstrated sensitivity to changes in postoperative pain intensity over time. In Study 4, convergent validity of the five scales and test retest reliability of the word-graphic rating scale were supported. The series of four studies provides strong evidence to support use of the word-graphic rating scale to measure pain intensity in pediatric populations. PMID- 1891623 TI - Gender stereotyping and nursing care. AB - The effect of gender stereotyping on nursing care was examined. Eight conditions were created in a posttest-only experiment by completely crossing patient gender (male/female) by memory load (low/high) by patient health status (stable/unstable). One hundred sixty nurses read the same patient vignette. The vignette differed in patient gender, memory load, and patient health status. The nurses then estimated the minutes needed for specific nursing interventions with the patient. Nurses planned significantly more ambulation, analgesic administration, and emotional support time for the male patient, despite the presence of individuating information. More accurate, effective nursing care is possible when nurses are aware of the effect of gender stereotyping on nursing care. PMID- 1891624 TI - More on MTMM: the role of confirmatory factor analysis. AB - This article is the second of two on the use of confirmatory factor analysis (CFA) as a method to assess construct validity. The construct validation criteria required by the conventional MTMM approach are satisfied only by certain ideal data sets, such as those in which the method variance of measures is very low. The CFA approach to multitrait-multimethod (MTMM) data is more general, in that violations of those stringent criteria can be managed. Another limitation of the conventional MTMM approach is that only a relatively small number of indicators can be examined by bivariate analysis. The economy of the CFA approach permits the analysis of a much larger number of indicators. In this article, a data set is analyzed using the CFA approach. Results are presented that illustrate the application of this statistical method. PMID- 1891625 TI - [Treatment of various frequently occurring periodontal problems]. AB - Some clinical factors of importance for handling of periodontal problems are discussed in this paper by means of case reports. Severe but localised alveolar bone loss, treatment of narrow or missing attached gingiva and periodontal abscess formation are briefly described. PMID- 1891626 TI - [Gingival hyperplasia in a heart transplant patient treated with cyclosporin A and nifedipine]. AB - Cyclosporin-A and Nifedipine-induced gingival enlargement have been reported to have similar clinical and histopathological features as phenytoin. The present case report describes the clinical course and treatment of a young heart transplant patient who developed gingival hyperplasia under both Nifedipine and Cyclosporin-A. After withdrawing Nifedipine from his daily medication and a second step of surgical excision, the patient presents no recurrence of gingival enlargement, 6 months post-treatment despite his Cyclosporin-A regimen and poor oral hygiene. PMID- 1891627 TI - [A case of oral rehabilitation]. AB - The success of the treatment of patients suffering from severe chronic periodontitis urges a tight complicity between dentist and patient. This article underlines the importance and the sequence of the treatment: medical anamnesis, initial periodontal examination, motivation of the patient for better oral hygiene, initial non-surgical treatment, follow-up of the healing, pre-prosthetic surgery, provisory and definitive prosthetic treatment, maintenance. It shows the results, 3 years after the treatment of a female patient, suffering from periodontitis in a terminal stage. PMID- 1891628 TI - [Motivation and maintenance in periodontal therapy. Experiences of a periodontal practitioner in Brussels]. AB - Periodontal disease is often a chronic and recurrent disease and therapy success is influenced by the quality of oral hygiene, professionally delivered maintenance and compliance of patients towards regular recall programs. In this paper the significance, objectives and organisation of maintenance in the periodontal practice are discussed and guidelines to minimize noncompliance are given. The responsibility of the dental corps in the organisation of maintenance in a qualitative and economically acceptable way is discussed. In order to provide our patients with important maintenance care, auxiliary dental personal, such as hygienists, should legally be allowed to work in the Belgian dental office. In a retrospective study, compliance of patients towards maintenance in a periodontal specialist practice in Brussels was investigated. Of 274 patients enrolled in a recall program only 65% reacted after receiving a recall reminder. Patients treated surgically responded in 76.5% and 47.2% of the patients treated by non-surgical means returned; there was a slight but statistically significant difference in compliance between Dutch (67.5%) and French (59%) speaking patients. PMID- 1891630 TI - [The clinical effects of Plax remains to be demonstrated]. AB - Experimental data concerning the plaque removal capability of the prebrushing rinse Plax tend to show only a limited if any effect on dental plaque accumulation. Its effect on gingivitis has only been studied sporadically, but it seems that Plax is not better than placebo in reducing or preventing the amount of gingivitis. PMID- 1891629 TI - [Chemical control of plaque: comparative review]. AB - Plaque control can be achieved by mechanical means. Since plaque removal can be laborious and difficult, chemical agents became important adjuncts to traditional oral hygiene procedures. Chlorhexidine is one of the synthetic antiseptics that has a unique antiplaque effect and 0.2% chlorhexidine can achieve a practically complete plaque control. It has one negative effect namely an extrinsic brown yellow staining. Listerine has proven its ability to reduce plaque and gingivitis in a moderate way. Hexetidine has a greater antiplaque effect in combination with zinc and can be compared with a 0.1% chlorhexidine. Povidone-iodine can not be used to keep plaque at low levels. Sanguinarine can reduce plaque accumulation when the toothpaste and mouthrinse are used together. H2O2 is an antiplaque agent but has some negative effects such as ulcerations... One can conclude that the use of a chemical agent cannot replace a good mechanical plaque control but is rather an adjunct to oral hygiene under certain conditions. PMID- 1891633 TI - [Alcoholic hepatopathy and nutrition]. PMID- 1891631 TI - [The treatment of dentin hypersensitivity]. AB - Dentine hypersensitivity is caused by a change in fluid flow in the dentinal tubules, which excites nerve endings located in the dentinal tubules and at the pulp-dentine border area. Traumatic oral hygiene procedures, excessive use of acid containing dietary fluids and certain dental treatments have been implicated in the occurrence of dentine hypersensitivity. Initial treatment relies on a positive doctor-patient relationship and the use of a desensitizing toothpaste containing strontium chloride, potassium nitrate or sodium citrate. If no relief is obtained, further treatment attempts need to be undertaken by the dentist- application of fluoride varnishes, potassium oxalate, resins or adhesives. PMID- 1891632 TI - [Endodontic-periodontic problems]. AB - The relationship between periodontium and endodontium. This article discusses the influence of periodontal pathology and therapy on the dental pulp and endodontium. It also gives a differential diagnosis description of perio-endo lesions and the implications of the perio-endo relationship for treatment. PMID- 1891634 TI - [Cerebral contusions. Study of 182 cases]. AB - Clinical cases were selected in which cerebral contusions were the only visible lesions in CT scan on admission over the period from January 1983 and December 1985. The following characteristics were evaluated: Age, sex, conscience level (Glasgow) at admission, early post-traumatic epilepsy, focal signs, lesion mechanism, cranial fracture, as well as CT scan in which specific signs of bad prognosis were analyzed. According to the evolution of conscience level 3 groups of patients were established: Group 1 "no coma", group 2 "coma with lucid interval", group 3 "coma without lucid interval" and were correlated with the previously mentioned characteristics. The highest mean age (59.2 years) appeared in group 2. In 75% of patients in group 3 a traffic accident was the lesion mechanism. Admission CT scan showed that the severity is related to bad prognosis signs (displacement of middle line, lack of 3rd ventricle, and basal cisterns and multiple lesions). Mortality was approximately 70, 80 and 90% whether they had one, two, or three bad prognosis signs at admission CT scan. PMID- 1891635 TI - [Usefulness of CT scan in the diagnosis of pulmonary aspergilloma]. AB - Early diagnosis and precise anatomical localization of aspergillomas are essential for an effective treatment of their complications. We have evaluated the usefulness of thorax CT scan in the fulfillment of these objectives. Nine consecutive patients were studied with a presumable diagnosis of pulmonary aspergilloma. A thorax CT scan was performed in all patients (sections every 5 to 10 mm) in lying position and with lateral mobilizations. This technique allowed to rule out as fibrotic lesions some of the images previously attributed to mycetomas by conventional X-ray. On the other hand it helped to identify small size aspergillomas, to precise their localization and to demonstrate the possible communication between the main cavity and bronchial tree. In three patients who died in the period immediately following the study an excellent correlation between CT scan and underlying pathological lesions was observed. PMID- 1891636 TI - [Active and inactive forms of cerebral cysticercosis. Study of 10 cases]. AB - Ten cases of neuro-cysticercosis attended in our hospital over the last five years are presented. Six patients presented non-active parenchymatous calcifications of which four manifested epilepsy, one dementia caused by hydrocephalus and one other was asymptomatic. Two patients presented active intraparenchymatous cysts with a clinic of epilepsy. One patient presenting cisternal -ventricular-parenchymal involvement and another with ependymal meningeal-parenchymal involvement, both suffered of psychiatric alterations. Ataxia and pyramidal deficits. The two patients with active parenchymal form were treated with Praziquantel obtaining a complete cyst remission (normal cranial Ot scan, in one case normal NMR) and neurological clinical symptoms. Two more patients treated with Praziquantel suffering ventricular and meningeal ependymal involvement presented little or no response to this treatment. PMID- 1891637 TI - [Primary lymphoma in the central nervous system treated with radiotherapy and chemotherapy. A case report]. AB - A case of primary lymphoma of the central nervous system treated successfully with radiotherapy and systemic and intrathecal chemotherapy is described. The efficiency of the combination of radiotherapy with chemotherapy in the treatment of primary lymphoma of the central nervous system is discussed. PMID- 1891638 TI - [Decreased insulin receptor number and affinity in subcutaneous adipose tissue in a patient with primary hyperaldosteronism]. AB - In the present work we study the binding of insulin to its receptors in adipocytes from subcutaneous adipose tissue of left hypochondria extracted during an adrenalectomy carried out in a patient with Conn's Syndrome (left adrenal adenoma), comparing it to insulin binding to its receptors in adipocytes from subcutaneous adipose tissue of right hypochondria, obtained during a cholecystectomy because of cholelithiasis (controls). According to our results, there is an evident decrease in insulin binding to its receptors in adipocytes of the patient with Conn's Syndrome in relation to control group. This decrease in binding would be based both in a decrease in insulin receptor number as in an affinity loss of these receptors for the hormone. These facts at the receptor level could be originating a decrease in tissue response to insulin and be the base for glucose intolerance observed in patients with this pathology. PMID- 1891639 TI - [A 57-year-old woman with stupor and skin lesions]. PMID- 1891640 TI - [Maculo-papular exanthema and brucellosis]. PMID- 1891641 TI - [Heterosexual transmission of HIV]. PMID- 1891642 TI - [Right ventricle dysplasia]. PMID- 1891643 TI - [Clinical usefulness of drug level monitoring]. PMID- 1891644 TI - [Nitrogen dioxide poisoning]. PMID- 1891645 TI - [Pneumothorax, pneumomediastinum and subcutaneous emphysema in P. carinii pneumonia]. PMID- 1891646 TI - [Septic thrombophlebitis of the portal vein. Presentation of a cryptogenic form]. PMID- 1891647 TI - [Acquired hypophosphatemic osteomalacia in a patient with idiopathic pulmonary hemosiderosis]. PMID- 1891648 TI - Seeing an old attitude in a new light. PMID- 1891649 TI - Gender differences in cardiac rehabilitation patients. AB - Gender differences in anxiety, self-efficacy, activity tolerance, and adherence were assessed in 101 patients (80 males, 21 females) with coronary artery disease consecutively admitted to three phase II cardiac rehabilitation centers. The percentage of women in rehabilitation is 20% lower than anticipated based on coronary morbidity data. On admission to rehabilitation, men were significantly better able to tolerate physical activity, were less anxious, and perceived themselves as having greater efficacy in enduring exercise and activities of daily living than women. During the first month of rehabilitation, 24% of males and 33% of females missed 1 week or more of scheduled sessions. There were no significant differences in demographic or diagnostic characteristics between sexes. PMID- 1891650 TI - Understanding the effects of a myocardial infarction on sexual functioning: a basis for sexual counseling. AB - Sexual counseling is an integral component of the rehabilitative process for clients who have experienced a myocardial infarction (MI). This article describes myths and fears concerning the dangers of resuming sexual intercourse after a heart attack, positions for intercourse, and the effects of intercourse on arrhythmias, angina, and blood pressure. The purpose is to provide the results of empirical research to dispel myths and fears and to consider the causes of sexual dysfunction, the changes MI brings about in sexual activity for men and women, and the effects of age, exercise, and antihypertensive drugs on the resumption of sexual activity. Guidelines are provided for conducting a sexual/cardiac history as part of the counseling model with specific information for the post-MI client. PMID- 1891651 TI - Rehabilitation of swallowing and communication following glossectomy. AB - Patients who have had surgical removal of part or all of the tongue are left with varying degrees of swallowing and speech deficiencies. The extent of resection, mobility of the residual tongue segment, and adequacy of the remaining structures determine the amount and type of deficiency. While communicative impairment and dysphagia commonly are seen in a rehabilitation setting, the problems of the glossectomy patient often are unique. This article reviews the anatomy and physiology of the oral and pharyngeal musculature, discusses the speech and swallowing of the glossectomy patient, and presents nursing considerations for successful rehabilitation. PMID- 1891652 TI - Brain injury rehabilitation settings: a gold mine for student and staff learning. AB - This article explores cognitive, psychomotor, and affective learning relative to the professional development of senior nursing students and staff in a long-term brain injury rehabilitation setting. Valuable opportunities for learning exist in this environment. Nursing students acquire a much different perspective toward caring for patients in rehabilitation settings than in acute care; they also gain tremendous opportunities to strengthen the clinical judgement and psychomotor skills applicable to most clinical work environments following graduation. In addition, they assume professional attitudes toward and interest in caring for long-term brain-injured patients as they work closely with expert rehabilitation nurses. When staff nurses interact with students, they receive reciprocal benefits. Staff nurses profit by refining and broadening the scope of their own practice; they also develop a positive self-image and a feeling of pride in their work. More importantly, staff nurses in a long-term brain injury rehabilitation setting regain the feeling that their daily efforts are really worthwhile. PMID- 1891653 TI - Analysis of a clinical situation using the Neuman Systems Model. PMID- 1891654 TI - Perception of health and use of health care services in a Swedish primary care district. A ten year's perspective. AB - In a study that covered ten years a questionnaire about perceived health and use of health care services was mailed each autumn to 1/60 representative samples of the population in Sollentuna, a Swedish primary care district. The majority of respondents thought that their health was good, and only a small minority reported themselves as quite, or very sick. Those assessments were stable during the ten year period. The tendency to visit the health services increased with the degree of severity of the illness. This increase was most marked in the case of visits to emergency departments and visits by appointment at hospitals, and least in the case of visits to private doctors and company/school physicians, while visits to doctors at health centres and to district nurses occupied an intermediate position. Thus, by including a simple question about perceived health in a questionnaire designed to measure use of health care services, important information about the relations between use of health services and health conditions could be obtained. PMID- 1891656 TI - Non-pharmacological methods reduce drug use in the treatment of hypertension. A two-year trial in general practice. AB - In a primary-care based study, 122 patients who were taking antihypertensive drugs took part in a two-year trial that aimed at establishing the feasibility of non-pharmacological methods in the treatment of hypertension in general practice. The patients could choose from among 14 non-pharmacological methods of blood pressure reduction. Increased physical exercise; weight reduction, low-sodium and low-fat diet, relaxation training, and home-monitoring of blood pressure were the most popular methods. The use of anti-hypertensive drugs was reduced by 55% in the participants, with the defined daily dose (DDD) being lowered from 1.18 to 0.55 (P less than 0.001). At the end of the study, 46% of the participants were free from anti-hypertensive drugs. Significant reductions occurred in body mass index (27.1 to 26.4 kg/m2, P = 0.001) and serum cholesterol (6.89 to 6.48 mmol/l, P less than 0.001). According to some measures used, the study group's experience of "quality of life" was not reduced. PMID- 1891655 TI - Maternal cigarette smoking, breast-feeding, and respiratory tract infections in infancy. A matched-pairs study. AB - The importance of mothers' smoking habits for the occurrence of respiratory tract infections (RTIs) in their children during their infant years was studied. A group of 28 infants of mothers who smoked was compared with 28 infants of non smokers. The pairs were matched with respect to mother's age, marital status, occupation, and parity. During their first year of life, the smokers' children were treated with antibiotics because of RTIs more often than the non-smokers' children (p = 0.046). The number of RTIs in the two groups were 38 and 19, respectively. However, infants of mothers who smoked were breast-fed for a shorter period than those of non-smokers (p = 0.028), the mean values being 4.5 and 6.7 months. PMID- 1891657 TI - Performance of cell counters in primary health care. AB - The results are presented from two external quality control surveys of cell counters in primary health care. The precision of haemoglobin measurements in the normal range was better than that obtained by conventional haemometers. The analytical quality of leucocyte analyses was about the same as that performed by hospital instruments. The precision of cell counters with respect to thrombocytes was poorer than that obtained on hospital instruments, especially in the lower level. Celldyn and Sysmex instruments performed best among the instruments examined. Reliable cell counter results were associated with medical laboratory technicians as operators of the instruments. To improve the analytical quality of the laboratory in primary health care, it appears necessary to establish an external quality assurance programme, including a laboratory consultancy service. PMID- 1891658 TI - Chronic posttraumatic syndrome after whiplash injury. A pilot study of 22 patients. AB - Chronic posttraumatic syndrome after whiplash injury presents several problems to the general practitioner, due largely to the discrepancy between the multiplicity of subjective symptoms and the poverty of objective findings. With the aim of analysing the symptoms and signs of this syndrome and of evaluating the significance of extended physical examination, 22 chronically disabled patients were investigated. The chronic syndrome is characterized by widespread symptoms, migrainous headache, and aggravation following physical activity. Extended physical examination, including an analysis of pain reaction elicited by palpation and a nerve tension test of the brachial plexus, together with negative X-ray examination, supports a common origin of symptoms in soft tissue injury and a disturbance of locomotor function. On the basis of this study we propose an alternative approach to diagnosis and care for these patients. PMID- 1891659 TI - Asymmetry in doctor-patient communication. PMID- 1891660 TI - Capitation fee or fee for service? PMID- 1891661 TI - Comparison of patients' and doctors' comments on video-recorded consultations. AB - To compare patient and doctor views of the consultation process, 46 consultations were videotaped in four primary health care centres. Twelve general practitioners and 46 patients participated. Later, the patients and the doctors (on different occasions) spontaneously commented on the recorded consultations. Qualitative methods were used for the analysis. The patients seemed to have a perspective oriented towards relationships, while the doctors were more oriented towards medical tasks. There was an association of power between the parties that implies a relationship of mutual dependency. The doctors depended on the patients to obtain the information they needed about the symptoms to be able to fulfil their professional task. The patients depended on the doctor to get their important needs satisfied; everything from a particular medicine to being treated as a human being. The major differences in the comments by the patients and the doctors reflected their different roles and the asymmetry in the relationship. PMID- 1891662 TI - General practitioners' attitudes to a recent change in their remuneration system. AB - The study examines the attitudes of general practitioners in Copenhagen to a recent change in their remuneration system from capitation to a mixed capitation and fee-for-service system. The study was based on two questionnaires, one before and one 18 months after the change, distributed to a primarily self-selected sample of 100 general practioners in Copenhagen City. The questionnaires provided information about certain basic characteristics of the respondents, attitudes to the new remuneration system as compared with the former, and possible changes in attitudes towards professional competence and responsibilities in secondary versus primary care. The majority of the respondents did not feel any changes under the new remuneration system in terms of diagnostic and curative possibilities and their relations to colleagues and patients. Attitudes to secondary versus primary care responsibilities also changed little. The majority felt that there had been an increase in their total work load, but also an improved economic situation in their practice. 21% felt that there was more competition with colleagues and 30% that doctor-patient relationships had suffered as a result of the introduction of a fee-for-service. PMID- 1891663 TI - Feasibility of a primary health care programme aiming at reducing cardiovascular and cerebrovascular risk factors among women in a Swedish community, Stromstad. AB - In the Swedish community of Stromstad, where the mortality from cardiovascular disease is high in the female population, all women aged 45-64 years were offered a health survey with the main purpose of screening for cardiovascular risk factors. Altogether 927 of 1084 women (86%) participated. Women with one or more risk factors were invited to attend a three-month course organized by the primary health care service to receive information about how they themselves could influence their risk factors by changing dietary and physical exercise patterns. At a follow-up survey three months later, the participants in the courses had significantly improved many of their risk factor values compared with the non participants. The improvement was still mainly present a year later. PMID- 1891664 TI - The erythrocyte sedimentation rate; its use and usefulness in primary health care. AB - Although the erythrocyte sedimentation rate (ESR) is frequently used and well known to both doctors and patients, the rationale behind its clinical use has been little explored. In this study we evaluated 559 consultations in general practice when an ESR was performed. It was most often done in response to musculoskeletal aches and pains, followed by respiratory tract problems, a general feeling of illness, and abdominal complaints. In half the cases it was used for diagnostic purposes, and in a third for monitoring progression of disease or treatment. In these cases the general practitioners found the test useful. Fourteen per cent were taken as a screening procedure, and were afterwards evaluated as being of little or no clinical value. In 60% of the consultations the test exerted its influence mainly by supporting or reinforcing the doctor's clinical opinion. In 11% the results were unexpected, and forced the doctor to reconsider. In 22% the results were felt to be of little or no clinical consequence. The ESR is perceived as very useful by the doctors when a specific diagnosis is considered. The test in itself is rather unspecific. Its major impact lies in its ability to help reinforce or lessen diagnostic probabilities. It is imperative, though, for the doctor to have a pretest hypothesis against which the test result can be evaluated. An ESR taken without an aim, or when somatic disease is unlikely, is of little or no clinical value. PMID- 1891665 TI - Determining cold-stress in full-term newborns through temperature site comparisons. AB - A secondary analysis of data from 120 full-term infants was performed to determine whether temperature relationships between sites could be used to identify cold-stress prior to core temperature decrease. Axillary and rectal temperature readings were taken every 30 seconds with standardized mercury-in glass thermometers, and the highest reading for axillary and rectal temperatures was used in data analysis. Three groups were identified when temperature site readings were compared: infants whose rectal temperature was higher than their axillary (group 1), infants who had equal axillary and rectal temperatures (group 2), and those whose axillary temperature was higher than the rectal reading (group 3). Further findings from data analysis suggested that infants whose rectal temperatures were within normal limits were either in a relatively neutral environmental state (group 1) or were maintaining their core temperatures through brown adipose tissue metabolism (group 3). PMID- 1891666 TI - Serenity: caring with perspective. AB - It is possible to care too much. Thus, there is a need to assist clients to achieve a state of caring with perspective (i.e., caring that lies in the gray area between excessive caring and not caring). Serenity is a concept that offers direction for attainment of this perspective; the concept of serenity is valued by many clients. Yet, the term is missing in nursing literature and the meaning of serenity in the literature that exists on the topic is vague. This article presents results of a concept analysis of serenity and discusses the relationship of serenity to the concept of caring. PMID- 1891667 TI - Nurses' experiences giving postmortem care to patients who have donated organs: a phenomenological study. AB - This study examined nurses' experiences in giving postmortem care to organ donors. A descriptive, phenomenological approach was used. Operating room, organ procurement agency, and critical care nurses were interviewed; audiotaped interviews were transcribed verbatim. Text-based analysis according to Colaizzi's (1978) approach was employed. Postmortem care took place in the context of the gift of the organs by the family, the tragedy of traumatic injury and resulting brain death of a young, healthy person, and procurement surgery. Nurses were saddened by the death of a donor, and viewed postmortem care as the opportunity to achieve closure with the patient. Nurses became temporary kin with the family and the patient. They respected the body, and saw giving after-death care as providing comfort even after death. As they cared for the patient throughout the experience, nurses confronted the dilemma of maintaining the brain-dead patient on life support until donor surgery. PMID- 1891668 TI - Adaptability: a personal resource for health. AB - Adaptation theories from the social and biological sciences have served well as building blocks for theory development in nursing. Recent consideration of the theories and their assumptions, however, has pointed to incongruencies with broadened conceptualizations of health and well-being. This paper reviews the development of stress, adaptation, and coping theory, and identifies congruencies and inconsistencies with the mission of nursing. The concept of adaptability is presented as a personal resource for health and self-care, a positive force for change, and empowerment for growth. PMID- 1891669 TI - [General process of aging]. AB - Genetic instability is considered to be a fundamental factor in the ageing process. This instability results from the accumulation of damage caused to DNA, and this is demonstrated by the relationship between longevity and DNA repair. However, the accumulation of simple somatic mutations does not explain all the experimental findings. We are forced to take into account, not only the instability of the genes, but also the instability of the expression of the genes. Knowing that the expression of genes depends on interactions between DNA and proteins, we can see that genetic instability is based, at least in part, on protein synthesis. Attention has recently been drawn to the mechanism of transcription and notably of messenger DNA division. At the level of translation, the rate at which messenger DNA is degraded and various elongation factors necessary for ribosome activity have also been implicated. Post-translational changes of proteins by glycosylation or oxidation may be involved in the progressive accumulation of errors, which finally leads to cell death. PMID- 1891670 TI - [Histologic signs of cutaneous aging]. AB - The changes induced by ageing of the skin are particularly visible in photo exposed areas, indicating the interaction between actinic factors and factors specific to the ageing process itself. The corresponding histological signs affect various structures: epidermis (thinning of the epidermis, reduced cell proliferation...), dermis-epidermis junction (disappearance of the microvilli with defective adhesion of the epidermis to the dermis), dermis (degeneration of elastin and collagen, which is photoinduced, and a moth-eaten appearance with loss of microfibrils as a result of time-related ageing), microcirculation (reduced vascularization, particularly visible in photo-exposed areas...) appendages. PMID- 1891672 TI - [Physiopathologic mechanisms of photo-induced cutaneous alterations]. AB - Ultraviolet rays are responsible for changes in the skin and in particular for actinic ageing. The harmful role of free radicals is now well established in this field. Defense against radicals is provided by enzymatic systems and by non enzymatic scavenger systems. Some drugs protect against radicals and this property is utilized in photo-induced dermatoses. PMID- 1891671 TI - [Clinical signs of cutaneous aging]. AB - Skin ageing depends on several, closely connected causes, including ageing obviously, but also on environmental factors, such as smoking and also, in women, on estrogen deficiency due to the menopause, but above all exposure to sunlight, particularly in fair-skinned individuals. The changes due to time-related ageing, thinner, withered skin are similar to those caused by the menopause, which also induces some signs of hyperandrogeny. Sun-related changes, which occur mainly on uncovered areas, vary so widely that some authorities prefer the terms "dermato heliosis" or "helio-dermatitis" to that of solar ageing. Solar elastosis is the most typical change and is visible on the face as a yellowish skin criss-crossed by deep wrinkles. On the neck and extended surfaces of the limbs, the skin is atrophied and often dyschromic. Excessive exposure to the sun is also responsible for most skin cancers, which are known to occur mainly on exposed parts. PMID- 1891674 TI - [Ovarian hormones and cutaneous aging]. AB - The fall-off in ovarian production of estradiol tends to accelerate skin ageing, just as it accelerates bone and vascular ageing. The absence of progesterone increases the impact of the androgens on the sebaceous glands, the body hair and hair on the head. The absence of estradiol slows the mitotic activity of the basal layer ot the epidermis, reduces the synthesis of collagen and probably that of elastic fibers. It contributes to the thickening of the general dermoepidermal junction and the degradation of the mechanical properties, notably of resistance of shocks. General hypoestrogenemia may be spontaneously attenuated by the local synthesis of estradiol in the adipose tissue. Estrogen treatment should be prescribed at a sufficiently high dose to be truly substitutive in order to produce a measureable effect. PMID- 1891673 TI - [Cutaneous senescence and carcinogenesis]. AB - A variety of clinical, topographical, histological, epidemiological and geographical arguments attribute to the effects of solar radiation and to ultraviolet rays (UV) in particular, a decisive role in the processes of cutaneous carcinogenesis. This carcinogenicity is part of a series of chronic changes affecting the integument which constitute heliodermatitis or photosenescence. The effects of UV are cumulative. DNA is the main target of UV rays. Man possesses several DNA repair systems. The hereditary malfunction of part of these systems result in xeroderma pigmentosum, which constitutes a pathological model of photocarcinogenesis. Intrinsic skin ageing (non photodependent) appears to promote this process of photocarcinogenicity by several mechanisms: summation of DNA changes, progressive deterioration of repair systems, dermal-epidermal atrophy, melanocytic changes, immuno-surveillance deficit. PMID- 1891675 TI - [Treatment of actinic aging with topical vitamin A acid in different concentrations]. AB - Vitamin A acid has been used for 20 years in the local treatment of acne. In 1986, Kligman published a description of the efficacy of this molecule against skin ageing. In 1987, we began a study which is still in progress. It is intended to confirm the beneficial effects already observed in photosenescence and to demonstrate them by non-invasive methods and by standardized photographs. This study was randomized and carried out under double blind. Each patient acted as her own control. The concentration administered was 0.025 per cent for 6 months and then 0.05 per cent. The patient was followed up every month for 6 months and then every 4 months. The results demonstrated a reduction in the number and depth of the wrinkles and a regression of the pigmented spots. Safety was excellent and all the patients were highly satisfied with the treatment. PMID- 1891676 TI - [Cutaneous electric stimulation in aging. Electroacupuncture of wrinkles following the procedure of Ph. Simonin]. AB - The electroacupuncture process developed by Ph. Simonin has been used in the treatment of slack skin and age wrinkles of the face and neck. At present, with data in hand on a large number cases and spanning several years, it appears that substantial improvements are obtained in some 70 percent of cases after 10 to 15 sessions, maintained by periodic booster sessions, without any side effects. Although the exact physiological process of tissue regeneration via electric stimulation is still imperfectly understood, the reappearance of collagen and elastic fibers in the treated areas seems probable. Comparable results, derived from the use of similar electrical currents, have been documented in a variety of treatments, e.g. consolidation of fractures or of non-union and congenital pseudarthrosis, beneficial effects in urinary incontinence or in neuropathology. PMID- 1891677 TI - [The injectable collagens. Technique of implantation, indications, limits]. AB - Collagen implants have extended our therapeutic possibilities: used either alone or as a complement to surgical methods, they are an answer to the demand of many patients (who are carefully selected on clinical and immunological criteria) for obvious short-term efficacy, the frequency of complementary injections to complete filling, depending on the location of the areas treated. The main reservation lies in the onset of phenomena of local delayed hypersensitivity, which appears to be reduced as far as possible by concomitant performance of the skin and serum tests for anti-collagen antibody. Human, placental collagen, which has not yet been marketed nor have the purified fluid silicones which are currently experiencing a revival of interest, may be the future hope for these often ignored allergies. PMID- 1891678 TI - Trauma reduction in rhinoplastic surgery. AB - Operative procedures for bony pyramid surgery of the nose, using micro-osteotomes to reduce surgical trauma, are described. Over the last seven years experience with this refined technique has shown a considerable reduction in postoperative ecchymosis and oedema. PMID- 1891679 TI - Diagnosis of nasal allergy to the house dust mite. AB - Twenty-five patients with perennial rhinitis and a positive skin prick test (SPT) for Dermatophagoides pteronyssinus (Dp) and Dermatophagoides farinae (Df) were submitted to nasal provocation and the radioimmunosorbent test (RAST) for specific IgE-antibodies. We found a significant correlation in the reaction to both allergen extracts for all parameters examined. In addition, there was a significant correlation among the SPT, the RAST and the nasal provocation for Dp and between the SPT and the RAST for Df. In patients with perennial rhinitis we recommend the combination of all three methods to differentiate unspecific rhinitis from an allergic rhinitis. Only the patients with proved allergic rhinitis could benefit from a specific hyposensitisation. PMID- 1891680 TI - Vasoactivity of endothelin in nasal blood vessels. AB - Endothelin (ET) is a newly described peptide that was isolated from the supernatant of cultured porcine aortic endothelial cells. Among the three isoforms of ET, the originally discovered ET-1 is the only one that exists in vascular endothelium. It is reported to be an extremely potent vasoconstrictor in a variety of blood vessels. Using in vitro bioassay technique, the vasoactivity of ET-1 in both canine and human nasal mucosa was investigated. ET produces a contraction which is slow in onset and sustained in the blood vessels both of the canine and the human nasal mucosa. The threshold of ET-1 in causing contraction was 10(-9) M (dog) and 10(-8) M (human). This response was turned out to be extracellular Ca(2+)-dependent, because either Ca(2+)-free medium or application of nifedipine almost abolished it. A subthreshold concentration of ET-1 enhances exogenously applied noradrenaline (NA)-induced contractions, but not endogenous NA-induced contractions caused by transmural electrical stimulation. As endothelium derived substances, such as ET-1 showed strong vasoactivity, endothelium may play an important role in maintaining vascular tension of the nasal blood vessels along with neural control. PMID- 1891681 TI - A comparison between intranasal budesonide aerosol and budesonide dry powder in the treatment of hay fever symptoms. AB - Sixty patients with seasonal allergic rhinitis due to birch pollen were enrolled in an open, randomized parallel group study. Efficacy and side effects were studied after intranasal administration of budesonide given as a freon propellant aerosol or as dry powder with a sniff actuated inhalation device. Medication started a few days before the actual peak pollen season and lasted for three weeks. The dose was 400 micrograms once daily. Efficacy was assessed daily by patient-rated symptoms scores and by nasal peak inspiratory flow measurements at the visits to the clinic. Safety was assessed by monitoring clinical adverse events. No clear changes in nasal symptom scores or nasal peak flow occurred during the pollen season in either treatment group as compared to the pretreatment period, although the pollen season was very difficult in Finland during the study, ad 12000 grains per m3. Substantial or total control of symptoms was achieved in 93% of the patients in the aerosol group and in 79% in the powder group. Side effects were minimal in both groups. We conclude that dry powder administration of budesonide is as effective and well tolerated as the aerosol in the treatment of seasonal allergic rhinitis. PMID- 1891682 TI - Frontal bone osteomyelitis complicating frontal sinusitis caused by Haemophilus influenzae type a. PMID- 1891683 TI - Some historical aspects of the surgical treatment of the infected maxillary sinus. AB - Sinus surgery probably originates from the time of the New Kingdom of ancient Egypt. Instruments were used to remove the brain through the nose as a part of the mummification process. The interest in the pathology of the maxillary sinus started to rise in the 17th century. Antral trephination for suppuration was the most common maxillary sinus operation in that period. An oro-antral fistula was often created by the extraction of a molar to drain the infected maxillary sinus daily. Later on the anterior wall of the maxillary sinus was opened through the canine fossa and was kept open for irrigation. Caldwell (1893), Scanes Spicer (1894) and later Luc in 1897 closed the canine fossa incision after an intranasal antrostomy and the removal of the infected mucosa. This so-called Caldwell-Luc procedure is still the most commonly used maxillary sinus operation today. After the introduction of the endoscopy in the beginning of this century endonasal surgery has been developed in the last decades into one of the important surgical procedures for maxillary sinus infections today. PMID- 1891684 TI - Endoscopic endonasal sinus surgery. Approaches and post-operative evaluation. AB - Recently, by using a rigid endoscope and a VIDEO system (CCD camera and TV monitor) for endonasal sinus surgery, surgical complications have been prevented. This is because a decrease in the dead angles achieves wide and clear visualisation of the site of manipulation of the paranasal sinuses, which have a delicate and complicated structure. Our endonasal sinus procedures under local anaesthesia consist of removal of pathologic mucosa within the anterior and posterior ethmoid sinuses, opening of the cellulae and establishment of sufficient communication between the ethmoid sinus and the maxillary and frontal sinuses. Even if pathologic mucosa is present in the maxillary sinus, we leave it intact and attempt to heal it by achieving good ventilation. The surgical technique often includes correction of septal deviations and conchotomy. In patients with moderate to severe sinusitis (62 cases, 102 examples) who underwent endoscopic endonasal sinusectomy by the same surgeon, X-ray studies of post operative changes of the maxillary sinus were performed. Fifteen cases showed excellent results, 47 good results, 30 fair results and 10 were unchanged. Clinical symptoms exhibited an overall improvement rate of 73%. Improvement of nasal discharge and nasal obstruction was more easily achieved than improvement of post-nasal discharge. PMID- 1891685 TI - Presentation of rhinosinugenic intracranial abscesses. AB - Intracranial abscesses secondary to rhinosinugenic disease are uncommon and the incidence is poorly documented. It is generally believed that individuals at risk of developing this complication can be identified by presenting clinical features. A ten year retrospective Scottish national survey 1976-1985 of intracranial abscesses was carried out. Clinical and or radiological evidence of nasal/paranasal aetiology in abscesses localised to the frontal lobe, extradural or subdural spaces allowed 23 surgery or autopsy confirmed abscesses to be classified as rhinosinugenic. 12 abscesses occurred in individuals aged 0-19 years, two in patients with risk factors for intracranial spread, 8 of 11 adults had similar predisposing features (p less than 0.01). This is a rare complication and individuals at risk in the first two decades of life can seldom be identified prospectively on clinical grounds. PMID- 1891686 TI - [A new Foundation for medical research, the Pierre CERNEA Foundation (under the auspices of the Fondation de France)]. PMID- 1891687 TI - [Diagnostic temporo-mandibular arthroscopy. Principle lesions, apropos of 50 case reports]. AB - Diagnostic arthroscopy is reserved to patients who suffer from internal temporo mandibular joint derangements resisting to conservative treatments. This technique allows an acute diagnostic approach to the intra-articular lesions of the superior compartment. PMID- 1891688 TI - [Value of MRI in the visualization of the meniscus in temporomandibular joints]. AB - Modern imaging techniques, among which nuclear magnetic resonance currently ranks first, have made it much easier to understand the internal disorders of the temporomandibular joint. While computed tomography still is the ideal technique for all bony affections in the articular region, especially for injuries. MRI now is an essential first-intention complementary examination. It allows assessing the location of the meniscus and very well defines the pathology being explored: reducible or irreducible dislocation of the meniscus, either purely anterior or anterolateral, the latter being better visible on coronal views (which are not systematically taken). The examination includes T1-weighted parasagittal views perpendicular to the axis of the condyle, taken with a surface coil (knee coil). Two sequences are performed, one with the mouth open and one with the mouth shut. The meniscus appears as a biconcave hypointense signal, which normally lies on the head of the condyle both when the mouth is open and when it is shut. T2 weighted sequences have the advantage of revealing possible effusion or intra articular adhesion between the capsule and the synovial membrane. They may also better demonstrate a possible myxoid degeneration of the meniscus. The considerable increase in scanning time required for these sequences accounts for their unfrequent use. The condition of the bone can also be assessed, but we find MRI less accurate than direct sagittal CT scans. The future prospects include shorter imaging times owing to fast-imaging sequences (short T1 with partial flip angle). PMID- 1891689 TI - [Metastases of malignant tumor in the jaw. Analysis of 30 case reports]. AB - 30 metastases of malignant tumors in jaws were retrospectively studied. They occurred more often in women than in men (17 F/13 H). In 21 cases, the primitive cancer was known and had been treated 1 to 4 years before. In the other cases (9), the bone metastasis led to the discovery of a latent tumor. Clinical signs and symptoms included swelling, pain, loosening of teeth, labio-mental anaesthesia and rarely pathologic fracture. Radiologically, all but two patients had radiolucent lesion. These metastases almost always involved the mandible (95% of cases) and in that bone, most often molar area and angle. Histologically, the majority of lesions were adenocarcinomas from breast (33%) and alimentary canal (stomach, colon). Epidermoid bronchial carcinomas were seen in 5 cases and malignant melanomas in 2 cases. Only one sarcoma of this series was arising from a liposarcoma of the thigh. In all but one patients, evolution was quickly lethal. PMID- 1891690 TI - [Metastatic localization in the buccal cavity. Case report and literature review]. AB - Metastatic tumors of oral cavity are uncommon. Mandibular localisation is the most frequent. Microscopic diagnosis and other metastatic localisations help the diagnosis we are reporting on. The report is on a case with prostatic and lung primitive tumors associated with gingivo-maxillary, femur and cutaneous metastasis. PMID- 1891691 TI - [Basocellular epitheliomas of the eyelids]. AB - On the basis of a retrospective study of 354 basal-cell epitheliomas of the eyelids, we present a study of the most frequently used treatments: surgery, conventional radiation therapy and curietherapy. The results of treatment, both functional and oncological, are generally satisfactory, whatever the method chosen, but with a set of arguments in favor of surgery. The major therapeutic indications are discussed, without formally ruling out any treatment. PMID- 1891692 TI - [Surgical problems arising from ethmoid adenocarcinomas]. AB - Adenocarcinomas are the most frequent ethmoid tumors. The only curative treatment at present is surgery. Potential extensions of these tumors require a wide exeresis. This is best ensured with an approach that is cranial and of the Cairns type at first, then in some cases facial and patterned on the Moure-Sebileau course of approach. This procedure demands the immediate reconstruction of the 3 levels involved: the dura mater, the bone and the mucosa of the nasal fossae. We reconstruct the dura mater with a pericranial flap, the bone with bone grafts, and the mucosa with a flap from the galea. PMID- 1891693 TI - [Medical treatment of osteoradionecrosis]. AB - The medical treatment of radiation-induced osteitis is advocated by all, with highly variable practical modalities. In our historical series, we have noted 12 good results out of 48 patients treated. In the light of R. Dambrain's work, we have used a procedure associating two antibiotics to Calcitonin during more than two months, with encouraging results. PMID- 1891694 TI - [Teleradiographic analysis of the face in facial asymmetry]. AB - The authors emphasize the interest of the frontal cephalometric analysis in facial asymmetries; principles of a simple cephalometric study are given. They analyse the mandibular abnormalities and his maxillary participation. Possibility of surgical treatment and postoperative control can be done. Three cases are presented. This method concerns post traumatic as well as congenital facial asymmetries. PMID- 1891695 TI - [Sphenoid fissure syndrome in orbital fractures. Case presentation and literature review]. AB - The superior orbital syndrome has been reported as a very rare complication of orbital fracture. In emergency clinical examination and computed tomography of the cranio-orbital region have provided diagnosis of the compression of the superior orbital fissure content by oedema and/or hematoma. These examinations have determined the type of cranio-orbital fractures and the absence of extra dural haemorrhage, optical nerve damage or compression, which required emergency treatment. After surgical treatment of the cranio-orbital fracture by temporal and transconjunctival approach, the orbital fissure syndrome has required supervision. The recovery of ophthalmoplegia has taken several months. Minor after effects have been observed for the patient reported. PMID- 1891697 TI - Bergen symposium on pediatric rheumatology. 12-15 May 1990, Bergen, Norway. Abstracts. PMID- 1891696 TI - [Metoclopramide intolerance and oral manifestations]. AB - Metoclopramide is a widely used product, which can accidentally cause acute dyskinesia, of which several forms may be observed, including dysarthria, tetany, spasmophilia, false cerebral vascular insult, trismus, hysteriform spell.... In all those cases, one should think of giving an antiemetic and of properly orienting history-taking, thus avoiding a longer stay in hospital that would not be justified. This is demonstrated by two patients recently admitted into the department of maxillofacial surgery and stomatology with maxillofacial signs related with the adverse effects of this kind of drug. PMID- 1891698 TI - The international workshop on cartilage. Oslo, Norway, 24-25 May 1990. Abstracts. PMID- 1891699 TI - [30-months extracorporeal electrohydraulic shock-wave lithotripsy of gallstones using the MPL-9000 at the Zurich University Hospital]. AB - The effect of extracoporeal shockwave lithotripsy (ESWL) in combination with oral chemolitholysis on gallstone clearance was tested in a prospective study. We used a non-waterbath lithotripter, and the patients were treated without general anesthesia or intravenous analgesia. They solely received oral or subcutaneous premedication. Within the 30 months study-period 78 patients were selected according to the "Munich-criteriae". At the end of the study period 33 patients were free of stones, 20 patients had residual fragments, and 25 patients stopped the therapy prior to complete stone clearance because of compliance (n = 11), or methodological (n = 14) problems. This includes 3 patients in whom the ESWL had to be discontinued because of pain. No severe complications were seen with the exception of one attack of acute pancreatitis, from which the patient recovered. The rate of stone clearance was analyzed using the life-table calculation according to KAPLAN-MEIER to weigh the follow-up time of each patient. At 12 months it revealed a stonefree rate of 70% in patients who did not discontinue the treatment because of methodological problems. The advantage of ESWL is the possibility to treat gallstones without general anesthesia or intravenous analgesia. However, the patient-population must be highly selected, and there is the risk of recurrence. PMID- 1891700 TI - [Developments in mitral valve surgery]. AB - Between 1987 and 1990 we operated on 104 patients for mitral valve disease. If possible the valve was reconstructed according to CARPENTIER's technique: 8 of 28 stenotic, 43 of 57 regurgitant and 2 of 7 mixed lesions were repaired. Twelve patients underwent re-replacement of a previously inserted mitral prosthesis. Six patients died early (7.8% after replacement, 8% after isolated replacement, 3.7% after repair and 2% after isolated repair). Five of these six patients were in NYHA class IV preoperatively. Seven patients died late after a mean observation period of 18 months (5 after replacement, 1 after double valve replacement and 1 after repair and multiple coronary bypass surgery). Prognosis is best for patients whose valve can be repaired and who are not already in NYHA class IV. The postoperative NYHA class for surviving patients is excellent (1.3 in the replacement group and 1.2 after repair). PMID- 1891701 TI - [Fibrinogen Bern III: a further case of hereditary fibrinogen variants with substitution A alpha 16 Arg----Cys]. AB - A heterozygous hereditary fibrinogen variant, fibrinogen Bern III, has been characterized. The proposita and her daughter showed prolonged thrombin time and reptilase time, as well as a markedly reduced fibrinogen concentration as determined by functional clotting assay. Fibrinogen was purified from the proposita's plasma and subjected to biochemical characterization. The delayed fibrin formation was shown to result from impaired release of fibrinopeptide A. Thrombin was found to cleave an extended fibrinopeptide A (A alpha 1-19) from the reduced polypeptide chains of the abnormal fibrinogen. Amino acid analysis of this fragment indicated that the arginine residue, located at the physiological thrombin cleavage site, was replaced by cysteine. The functional defect of the fibrinogen variant Bern III is due to the amino acid substitution A alpha 16 Arg- --Cys. PMID- 1891702 TI - Promoting positive outcomes. PMID- 1891703 TI - A study of the relationship among body position, bladder function and urine variables in spinal cord injured subjects. AB - Clinical observations of nurses working with spinal cord patients describe positional changes affecting diuresis. Research has not documented this phenomenon in detail. Knowledge of the timing of diuresis may allow more control over bladder management. The purpose of this descriptive pilot study was to determine the relationship among body position, timing of diuresis, urine volume, and fluid intake in spinal cord injured subjects. A convenience sample of six subjects with varying levels of spinal cord injury were studied. For five consecutive days, positional changes were determined during bed, wheelchair, and tilt activities. Fluid intake and urine volume, specific gravity, and colony count were measured. Data analysis using correlation and regression statistics revealed head and foot elevation and fluid intake may account for some variance but do not predict total variance in urine output. Future research to validate findings in a controlled setting may provide a scientific basis for bladder management. PMID- 1891705 TI - Can menopause cause autonomic dysreflexia? PMID- 1891704 TI - Research-the case for case studies. PMID- 1891706 TI - Lead in children's hair, as related to exposure in Tarragona Province, Spain. AB - Concentrations of lead were determined in the hair of 478 school children living in an industrial and an agricultural area of Tarragona Province, Spain. The influence of age, sex, hair colour and family occupation on the children's hair lead concentration was also evaluated. Girls had more lead in their hair than boys (10.54 vs 6.55 micrograms g-1), and the lead levels decreased with age. Lead concentrations in hair with respect to hair colour decreased in the order red, blond, brown, black. Family occupation was one of the most significant factors influencing the lead content of children's hair. Although the average lead content was higher in the industrial area (9.38 micrograms g-1) than in the agricultural area (7.80 micrograms g-1), this difference was not statistically significant. PMID- 1891707 TI - A comparative study of the lead and cadmium content of surface enamel of Belgian and Kenyan children. AB - Acid etch surface enamel microbiopsies were performed on teeth from 378 children aged 6-12 years; 318 of the children lived in Belgium, an industrialized country, and 60 lived in a rural part of Kenya. In addition to lead and cadmium, calcium and phosphorus were also quantitatively determined in the etch solutions. Calcium was chosen as an internal reference for the expression of the lead and cadmium concentrations and for the assessment of the etch depth. The mean lead level in surface enamel of the Belgian children was approximately eight times higher than that of the Kenyan children. The cadmium levels were not significantly higher. An appropriate regression model taking into account differences in etch depth showed that a significant decrease of lead and cadmium with etch depth occurred and that a significant correlation between lead and cadmium in surface enamel existed for the Belgian cohort. Moreover, the same mean calcium/phosphorus ratios were obtained for the Belgian and Kenyan surface enamel samples, and were found not to play a significant role in the calibration of the lead and cadmium levels. PMID- 1891708 TI - Comparative study of mercury accumulation in dolphins (Stenella coeruleoalba) from French Atlantic and Mediterranean coasts. AB - Total mercury concentrations (Hgt) have been determined in liver, kidneys, skeletal muscle, melon, stomach and intestine of 35 specimens of Stenella coeruleoalba stranded on French Atlantic and Mediterranean coasts. Very high mercury levels, with concentrations reaching 80 mg Hgt kg(-1) fresh weight (FW) in muscle and about 1500 mg Hgt kg(-1) FW in liver tissue, were observed. Liver has the highest concentration, followed by muscle and kidney. The lowest concentrations were found in the melon. The levels observed in the Mediterranean specimens are among the highest observed in marine organisms and confirm previous reports of high mercury levels in marine mammals from the Mediterranean. Comparison between Hgt accumulation levels in these two geographic groups of dolphins shows that Mediterranean individuals have much higher concentrations than specimens from the Atlantic. These differences provide additional confirmation for the higher Hgt concentrations observed previously in other pelagic species (tuna, sardine, anchovy, etc.) from the Mediterranean Sea. Taking into consideration the pelagic habitat of the dolphin and the local influence of anthropogenic mercury sources it seems reasonable to assume that the main source of the high mercury concentrations observed in Mediterranean biota is natural mercury deposits located in many regions of the Mediterranean basin. PMID- 1891709 TI - The acute toxicity of pulse-dosed, para-substituted phenols to larval American flagfish (Jordanella floridae): a comparison with toxicity to photoluminescent bacteria and predicted toxicity using log Kow. AB - The acute toxicity of nine para-substituted phenols was determined using a pulse exposure testing protocol and 8-day-old larval American flagfish (Jordanella floridae). Relative tolerance was assessed by determining the 2-h pulse exposure concentration causing 20 and 50% mortality (PE LC20 and PE LC50) over the subsequent 94 h. Four bioassays were run for each phenol and yielded the following mean PE LC20 values (mg 1(-1)) in descending order of toxicity: p aminophenol, 0.06; hydroquinone, 0.13; phenol, 0.70; p-nitrophenol, 0.81; p cyanophenol, 3.0; p-chlorophenol, 3.3; p-hydroxyacetophenone, 4.2; p hydroxybenzyl alcohol, 6.4; and p-hydroxybenzoic acid, 170. These toxicities did not correlate significantly with either previously reported toxicity values for the photoluminescent bacteria Photobacterium phosphoreum, or with the log octanol water partition coefficient. For some of the compounds, however, sensitivities were quite close to previously reported rainbow trout chronic no-observed-effect concentrations based on continuous exposure. Caution is urged with respect to applying "low-level" biota techniques or simple quantitative structure-activity correlations such as Kow when attempting to predict the toxicity of specific chemicals to fish. PMID- 1891710 TI - The foundations of research. PMID- 1891711 TI - New award debuts at NIH. PMID- 1891712 TI - Russian AIDS puzzle. PMID- 1891713 TI - Computer vision. AB - The field of computer vision is devoted to discovering algorithms, data representations, and computer architectures that embody the principles underlying visual capabilities. This article describes how the field of computer (and robot) vision has evolved, particularly over the past 20 years, and introduces its central methodological paradigms. PMID- 1891714 TI - Rel-associated pp40: an inhibitor of the rel family of transcription factors. AB - The Rel-associated protein pp40 is functionally related to I kappa B, an inhibitor of the transcription factor NF-kappa B. Purified pp40 inhibits the DNA binding activity of the NF-kappa B protein complex (p50:p65 heterodimers), p50:c Rel heteromers, and c-Rel homodimers. The sequence of the complementary DNA encoding pp40 revealed similarity to the gene encoding MAD-3, a protein with mammalian I kappa B-like activity. Protein sequencing of I kappa B purified from rabbit lung confirmed that MAD-3 encodes a protein similar to I kappa B. The sequence similarity between MAD-3 and pp40 includes a casein kinase II and consensus tyrosine phosphorylation site, as well as five repeats of a sequence found in the human erythrocyte protein ankyrin. These results suggest that rel related transcription factors, which are capable of cytosolic to nuclear translocation, may be held in the cytosol by interaction with related cytoplasmic anchor molecules. PMID- 1891715 TI - Requirement of microfilaments in sorting of actin messenger RNA. AB - Specific messenger RNAs (mRNAs) can be sequestered within distinct cellular locations, but little is known about how this is accomplished. The participation of the three major cellular filaments in the localization of actin mRNA was studied in chicken embryo fibroblasts. Movement of actin mRNA to the cell periphery and maintenance of that regionalization required intact microfilaments (composed of actin) but not microtubules or intermediate filaments. The results presented here suggest that actin-binding proteins may participate in mRNA sorting. PMID- 1891717 TI - Viral persistence in neurons explained by lack of major histocompatibility class I expression. AB - Viruses frequently persist in neurons, suggesting that these cells can evade immune surveillance. In a mouse model, 5 x 10(6) cytotoxic T lymphocytes (CTLs), specific for lymphocytic choriomeningitis virus (LCMV), did not lyse infected neurons or cause immunopathologic injury. In contrast, intracerebral injection of less than 10(3) CTL caused disease and death when viral antigens were expressed on leptomeningeal and choroid plexus cells of the nervous system. The neuronal cell line OBL21 expresses little or no major histocompatibility (MHC) class I surface glycoproteins and when infected with LCMV, resisted lysis by virus specific CTLs. Expression of MHC heavy chain messenger RNA was limited, but beta 2-microglobulin messenger RNA and protein was made normally. OBL21 cells were made sensitive to CTL lysis by transfection with a fusion gene encoding another MHC class I molecule. Hence, neuronal cells probably evade immune surveillance by failing to express MHC class I molecules. PMID- 1891716 TI - Cloning of complementary DNA encoding a functional human interleukin-8 receptor. AB - Interleukin-8 (IL-8) is an inflammatory cytokine that activates neutrophil chemotaxis, degranulation, and the respiratory burst. Neutrophils express receptors for IL-8 that are coupled to guanine nucleotide-binding proteins (G proteins); binding of IL-8 to its receptor induces the mobilization of intracellular calcium stores. A cDNA clone from HL-60 neutrophils, designated p2, has now been isolated that encodes a human IL-8 receptor. When p2 is expressed in oocytes from Xenopus laevis, the oocytes bind 125I-labeled IL-8 specifically and respond to IL-8 by mobilizing calcium stores with an EC50 of 20 nM. This IL-8 receptor has 77% amino acid identity with a second human neutrophil receptor isotype that binds IL-8 with higher affinity. It also exhibits 69% amino acid identity with a protein reported to be an N-formyl peptide receptor from rabbit neutrophils, but less than 30% identity with all other known G protein-coupled receptors, including the human N-formyl peptide receptor. PMID- 1891718 TI - Autoassociation and novelty detection by neuromechanics. AB - Many biomechanical systems contain ball joints with several elastic actuators (muscles) obliquely attached to the links. The problem of calculating the optimum actuator commands to achieve a desired link orientation is a difficult one for any control system; however, the elasticity of the actuators may be part of the solution. Mechanoreceptors such as those found in muscles and tendons are capable of performing operations that can be regarded as autoassociation and novelty detection, respectively, by minimization of potential energy. The information provided by such sensors may then be exploited for optimization of muscle coordination. PMID- 1891719 TI - Production of erythropoietin in the kidney. PMID- 1891720 TI - Erythropoietin titers in health and disease. PMID- 1891721 TI - Erythropoietin ontogeny and organ distribution in mice. PMID- 1891722 TI - Regulation of the erythropoietin gene in Hep 3B cells. PMID- 1891724 TI - Hello, central... PMID- 1891723 TI - Physiologic determinants of erythropoietin production. PMID- 1891726 TI - Massive abuse. PMID- 1891725 TI - Missing members. PMID- 1891727 TI - HIV-related characteristics of migrant workers in rural South Carolina. AB - After finding human immunodeficiency virus (HIV) infection in a migrant worker named as a syphilis contact, the South Carolina Department of Health and Environmental Control offered HIV counseling and testing and syphilis screening to migrant workers in the surrounding two-county area. In addition, a brief questionnaire was administered to document demographics and risk behavior. Of the 265 workers aged 16 and older in 15 migrant camps, 198 (75%) consented to the survey and testing. Of the 198 tested, 85% were male and 75% single. The median age was 39, with a range of 16 to 69 years. Twenty-five (13%) were HIV antibody positive, and 32 (16%) had reactive serologic tests for syphilis. Of the 166 workers who reported the frequency of condom use, 77 (46%) indicated they never use condoms. We conclude that there is a relatively high rate of HIV infection in these rural South Carolina migrant workers, whose behavior puts them at risk for HIV infection and other sexually transmitted diseases. PMID- 1891728 TI - Epidemiology and clinical characteristics of tularemia in Oklahoma, 1979 to 1985. AB - We studied the clinical and epidemiologic characteristics of tularemia in 165 Oklahomans from 1979 to 1985. The ulceroglandular form of the disease was most common (60%), followed by typhoidal (18%), glandular (15%), oropharyngeal (7%), and oculoglandular (1%) forms. The male-female ratio was 3.7:1, and the highest rates of disease were found in the age groups 5 to 14, 35 to 44, and 55 to 74. Ticks were most frequently implicated as the source of infection (84/154 [55%]), followed by rabbits, (58/154 [38%]). Seventy percent of the patients were hospitalized, and four (2.5%) died. The annual number of patients who reported that rabbits were their probable source of exposure to Francisella tularensis and the estimated number of rabbits harvested (ie, killed by hunters) for the year correlated closely with the total number of cases reported from year to year. PMID- 1891729 TI - Train versus pedestrian accidents. AB - Railroad-related trauma has been associated with injuries causing considerable morbidity. This is a retrospective study of 15 consecutive patients who were run over by trains. The initial injury produced a traumatic amputation of 10 extremities in eight patients. Limb salvage in two other patients with severe fractures failed, and subsequent lower extremity amputation was required. Despite efforts to salvage the most distal tissue possible, 8 of 12 extremities amputated in the acute traumatic period required revision to a more proximal level. Alcohol ingestion was involved in 13 of the 15 incidents in the study. No patient received posthospitalization alcohol rehabilitation. In addition, despite the young age of the patients in this series, only one patient was rehabilitated to a prosthetic ambulator. PMID- 1891730 TI - Pectus excavatum: a 15-year perspective. AB - Pectus excavatum is relatively uncommon. Our experience with 177 children during a 15-year period produced changes in our surgical technique, which now includes a small transverse incision, minimal subcutaneous flap elevation, a muscle-relaxing incision over the fifth costal cartilage, complete resection of involved cartilage, use of Adkins' strut, suspension of sternum to strut, taut reefing of intercostal muscle, no tubes or drains, epidural analgesia, a patient-controlled analgesia device postoperatively, and eventual strut removal. Use of the evolved technique gives excellent cosmetic results, good functional results with minimal discomfort, and a shorter convalescent period. PMID- 1891731 TI - Accelerated fractionation radiation therapy for advanced squamous cell carcinoma of the head and neck. AB - We treated 14 patients who had advanced head and neck cancer with an accelerated fractionation schedule of irradiation consisting of two fractions given 6 hours apart. In the morning a volume of 1.7 Gy was given to an area that encompassed the entire tumor, enlarged lymph nodes, and all areas at risk for microscopic disease. Six hours later, 1.1 Gy was given to an area that included only the tumor and any enlarged lymph nodes, with a 2-cm margin. The treatment was well tolerated; of the 13 patients who completed therapy, six did not require a break in therapy, and seven patients did. The median rest period was 2 days. There was no grade 4 toxicity. Grade 3 toxicity included skin changes (one case), mucositis (two), dysphagia (two), weight loss (three), and a decrease in the hemoglobin level (one case). The response rate in the 13 who completed therapy was 13/13 (100%); 11 of the 13 (83%) had a complete response. Only one of the 11 who achieved a complete response had failure at the primary site. At a median follow up of 24 months, the absolute survival was 7/13 (54%) and the corrected survival was 7/10 (70%). This technique permits radiation therapy to be given on an accelerated schedule without a planned break in treatment. The overall response rate and survival at 2 years was excellent. PMID- 1891732 TI - Hand function in patients with diabetes mellitus. AB - Using validated clinical tests and standardized controls, we measured hand function in diabetic subjects. Fifteen diabetic patients (median age 48 years), all having used insulin for a minimum of 5 years, were randomly selected from inpatient and outpatient services of an academic medical center. Testing was done on an outpatient basis. The three hand function tests used were the Purdue Pegboard, O'Connor Tweezer Dexterity, and Smith Hand Function. A symptom questionnaire was also included in the study. Function was significantly decreased in the diabetic group, and the decrease was out of proportion to their own subjective pretest assessments. These findings may have implications for occupational performance as well as activities of daily living. PMID- 1891733 TI - Hyponatremia among older individuals. PMID- 1891734 TI - Curative potential of primary whole-abdomen irradiation in ovarian carcinoma. AB - Ovarian carcinoma remains a leading cause of cancer mortality in American women. The identification of active chemotherapy drugs and regimens has resulted in much less frequent use of radiation therapy at a time when technical and conceptual advances have been made. Unfortunately, the shift from radiotherapy to chemotherapy has not produced a discernible improvement in patient survival. Retrospective and prospective data suggest that whole-abdomen irradiation offers curative potential in patients with nonbulky residual disease after surgical cytoreduction. Its use should therefore be reconsidered as a primary adjuvant therapy in properly selected patients. PMID- 1891735 TI - Magnetic resonance imaging in the evaluation of knee injuries. AB - To better define the role of magnetic resonance imaging (MRI) in the evaluation of knee injuries, we analyzed 10 recently published articles comparing MRI and arthroscopy in the detection of meniscal and anterior cruciate ligament tears. Sensitivity (SN), specificity (SP), positive predictive value (PPV), and negative predictive value (NPV) for medial meniscus (MM) tears, lateral meniscus (LM) tears, and anterior cruciate ligament (ACL) tears were either obtained or calculated from data contained in each article. The medians of measurements for MM tears were 97% SN, 89% SP, 88% PPV, and 96% NPV. Measurement medians for LM tears were 85% SN, 94% SP, 86% PPV, and 95% NPV. ACL tear measurement medians were 100% SN, 96% SP, 80% PPV, and 98% NPV. High NPVs were found in several studies, many of which were 100%. The high NPV of MR imaging suggests that diagnostic arthroscopic surgery is not necessary in the evaluation of patients with negative MRI studies. The superior sensitivity of MRI in detecting frank posterior horn tears, intrasubstance meniscal tears, and significant incidental findings also suggests that screening MRI scans can facilitate preoperative planning. PMID- 1891736 TI - Clostridium septicum myonecrosis and sepsis in the absence of trauma. PMID- 1891737 TI - Varicose veins: a reappraisal from a global perspective. PMID- 1891738 TI - Aortoiliac dissection after percutaneous insertion of an intra-aortic balloon pump. AB - Aortic or aortoiliac dissection may complicate percutaneous intra-aortic balloon pump insertion in various ways. Thrombosis can escape clinical recognition if no major obstruction develops. Death due to perforation after dissection is not uncommon. In this case study, aortoiliac dissection led to bilateral iliac artery stenosis, an unusual complication of percutaneous femoral cannulation for insertion of a balloon pump. PMID- 1891740 TI - Spontaneous internal carotid artery dissection shown by magnetic resonance imaging. AB - We have reported a case of spontaneous dissection of the internal carotid artery, with MRI and angiographic findings. We conclude that MRI is a beneficial noninvasive test for the detection and study of carotid artery dissection. PMID- 1891739 TI - External iliac artery rupture during angioplasty: control by balloon tamponade. AB - Transluminal angioplasty, particularly of stenoses of the iliofemoral arteries, is an excellent technique with a success rate greater than 90%, an overall complication rate of less than 5%, and a low incidence of major complications. Of these major complications, arterial rupture is one of the most urgent. We have presented a case of external iliac artery rupture during angioplasty that graphically demonstrates the value of balloon tamponade in managing this potentially catastrophic event. The angiographer's sensitivity to the possibility of arterial rupture and prompt management, combined with close collaboration with the vascular surgeon, can lead to a good clinical outcome. PMID- 1891741 TI - Severe frostbite caused by Freon gas. AB - We have reported a case of severe frostbite due to direct exposure to liquid Freon gas (monochlorodifluoromethane), a fluorinated hydrocarbon widely used as refrigerants, propellants, and industrial solvents. The patient was treated for severe third- and fourth-degree frostbite to the hand. The severity of the injury was apparently the result of direct through-and-through injury from exposure to the liquid (boiling point -40.5 degrees C) and a possible systemic vasoconstrictive effect on arterial smooth muscle due to inhalation of Freon gas. PMID- 1891742 TI - Reactive arthritis due to hidradenitis suppurativa mimicking osteomyelitis. AB - We have reported a case of erosive arthritis of the hand preceding the appearance of hidradenitis suppurativa in the ipsilateral axilla, which was mistaken for osteomyelitis. Recognition of this presentation is important to avoid unnecessary invasive diagnostic procedures and to initiate prompt treatment directed at the underlying cause. PMID- 1891743 TI - Large vessel occlusion with vasculitis in systemic lupus erythematosus. AB - Patients with SLE may have acute large vessel occlusion due to vasculitis and/or circulating antiphospholipid antibodies, as illustrated by the case we have reported. Unfortunately, delayed medical attention led to gangrene of the foot and amputation. Early recognition and appropriate treatment may significantly decrease morbidity and mortality. Medical treatment may include corticosteroids, thrombolysis, anticoagulation, or immunosuppression. PMID- 1891744 TI - Drug-resistant Nocardia asteroides infection in a patient with acquired immunodeficiency syndrome. AB - We have reported what we believe to be the first case of disseminated infection due to a multiply drug resistant strain of Nocardia asteroides in a patient with the acquired immunodeficiency syndrome and concomitant disseminated histoplasmosis. This strain of the organism fits a pattern of susceptibility that is rare among N asteroides isolates in general and has been called the type 5 pattern, described as a resistance to broad spectrum cephalosporins, ciprofloxacin, and all aminoglycosides except amikacin. The recognition of disease due to this group of organisms is especially important in patients with AIDS because sulfonamides, considered the drugs of choice for treatment of N asteroides infection, are associated with a high incidence of adverse effects in these patients. PMID- 1891745 TI - Testicular abscess caused by Salmonella typhi. AB - This case, which we believe is the first report of a bacteriologically proven infection of the testis by Salmonella typhi, illustrates the occurrence of this complication in the convalescent phase of typhoid fever and the absence of a clinically evident preceding bacteremic phase. The case also emphasizes the need for prolonged antibiotic therapy and the role of surgery in treatment of relapses. PMID- 1891746 TI - Ofloxacin-induced acute severe hepatitis. PMID- 1891747 TI - Liver function in alcoholic patients. PMID- 1891748 TI - Segmental infarction of the greater omentum. PMID- 1891749 TI - Loss of dystonia as a sign of myasthenia. PMID- 1891750 TI - [Magnetic resonance tomography in white matter diseases]. PMID- 1891751 TI - [Intraoperative identification of the trigeminal cavity]. PMID- 1891752 TI - [Sonographic organization of liver segments and its importance for liver segmental resection]. PMID- 1891753 TI - [Comparative studies of urinary incontinence using lateral cysturograms and urethrocystotonometry]. PMID- 1891754 TI - Management of patients aged over 60 years with supratentorial glioma: lessons from an audit. AB - This audit of clinical management confirmed the poor prognosis for patients (n = 80) aged over 60 years with a diagnosis of supratentorial glioma. The median survival time after diagnosis was 9 weeks following steroids and 7 weeks after biopsy and steroids. Cytoreductive surgery and radiotherapy improved median survival time by a maximum of 16 weeks, but there was significant morbidity in some patients undergoing craniotomy. Although 92% of the biopsied lesions were either glioblastoma or anaplastic astrocytoma, the median survival of these patients was similar to the 8% of patients confirmed as having intermediate grade astrocytoma. Patients presenting with minimal functional deficit (WHO grade I or II) had longer median survival times than those presenting in poor condition (WHO grade III or IV). In this series there was no relationship between management undertaken and clinical status of the patient. The 9% of the cohort that survived 1 year were treated in a variety of ways. This audit, together with results from other studies, suggests that a prospective clinical trial of different management regimes in elderly patients with supratentorial gliomas is needed. Since median survival time in the most intensively treated patients will be around 6 months, treatment evaluation must consider the quality of life provided. PMID- 1891755 TI - Efficacy and toxicity of thromboxane synthetase inhibitor for cerebral vasospasm after subarachnoid hemorrhage. AB - The efficacy and possible side effects of thromboxane A2 (TXA2) synthetase inhibitor in the treatment of cerebral vasospasm after subarachnoid hemorrhage (SAH) were assessed for 24 patients who presented with grades I to IV of the Hunt and Hess classification. All patients underwent aneurysmal clipping within 48 hours after SAH. Postoperatively, TXA2 synthetase inhibitor, Cataclot [sodium (E) 3-[p-(1H-imidazol-1-ylmethyl)phenyl]-2-propenoate] was administered to 13 patients by continuous drip infusion at a dose of 1 microgram/kg/min for 8 to 14 days (group A). The remaining 11 patients did not receive this drug (group B). Of the 13 patients in group A, seven patients (54%) showed no symptomatic vasospasm after SAH. Four patients (31%) developed a transient deterioration of consciousness and/or motor disturbance. Three of these patients fully recovered, while one of them showed a mild neurological deficit on discharge. One patient (8%) developed permanent dysphasia and hemiparesis as a result of ischemic brain damage due to vasospasm. One patient (8%) died of the side effect. On the other hand, of the 11 patients in group B, only three (27%) showed no symptomatic vasospasm. One (9%) patient presented a transient neurological deficit but fully recovered upon discharge. Four patients (36%) showed permanent neurological deficits, although they all could lead an independent life after discharge. The three remaining patients developed a severe disturbance of consciousness caused by ischemia due to vasospasm, and two of them died within 1 month after the onset of SAH. In the group treated with Cataclot, two patients developed an epidural hematoma late during the administration of the drug. Of these two, one patient died of increased intracranial pressure that was accelerated by the complication. These results indicate that TXA2 synthetase inhibitor is effective in not only decreasing the occurrence of symptomatic vasospasm but also reducing the neurological deterioration due to vasospasm after SAH. However, this drug has a hazardous side effect in that it may promote a tendency to bleed, which caused death in one of our patients. PMID- 1891756 TI - Characterization of the mononuclear cell infiltrate and HLA-Dr expression in 19 oligodendrogliomas. AB - We have studied frozen tissue from 19 oligodendrogliomas with a panel of antibodies to lymphocytes and their subsets, macrophages, natural killer cells, and HLA-Dr antigens. Macrophages were detected in moderate numbers in 60%-100% of tumors depending on the antibody used. T lymphocytes were fewer in number than macrophages and were present in 62% of cases. Most of the T lymphocytes were of the CD8 phenotype. CD4 lymphocytes were very few in number and present in only 18%. B cells and natural killer cells were absent from all cases. HLA-Dr antigens were expressed by macrophages in all cases but never on tumor cells. The implications of these findings are that macrophages and, to a lesser extent, CD8 lymphocytes are the predominant cells infiltrating oligodendrogliomas and that they may exert cellular immune functions. PMID- 1891757 TI - Traumatic carotid-cavernous sinus fistula associated with an intradural pseudoaneurysm: a case report. AB - A case of traumatic carotid-cavernous sinus fistula (CCF) associated with an intradural pseudoaneurysm is reported. A 42-year-old man developed traumatic CCF after severe head trauma. Cerebral angiography demonstrated a direct CCF associated with an intradural pseudoaneurysm at the C2 portion. Transarterial balloon embolization of the CCF caused severe subarachnoid hemorrhage. A CCF with an intradural pseudoaneurysm is life-threatening and requires emergency treatment. However, balloon occlusion in such cases is contraindicated because of possible rupture of a pseudoaneurysm. Trapping or a direct surgical approach is the treatment of choice. PMID- 1891758 TI - Lymphocytic adenohypophysitis: an immunohistochemical study. AB - Lymphocytic adenohypophysitis is a rare inflammatory disorder of the anterior pituitary gland. In some cases, there is evidence of concurrent autoimmune disease. We present the case of a 39-year-old woman who developed visual disturbance during the early postpartum period. Magnetic resonance imaging revealed an intrasellar mass with suprasellar extension. Study of the tumor tissue showed diffuse infiltration of the entire pituitary gland by lymphocytes and plasma cells. Immunohistochemical examination revealed that the majority of the infiltrating lymphocytes were T cells that might have modulated the immunoreaction to the anterior pituitary gland. We suggest that the disorder is related to cell-mediated immunity as well as humoral immunity. PMID- 1891759 TI - Sickle cell disease and aneurysmal subarachnoid hemorrhage. AB - While neurological complications are common in sickle cell disease, aneurysmal subarachnoid hemorrhage has been rarely reported. A case is presented of a young man with sickle cell disease and subarachnoid hemorrhage found to have two mid basilar aneurysms, the largest of which had bled. Available literature suggests that this patient may be quite representative as nearly one half of documented cases have been noted to harbor multiple aneurysms, and posterior circulation involvement appears to be common. These anatomic features may relate to the pathophysiology of arterial destruction common in sickle cell disease. PMID- 1891760 TI - Temporary clipping in aneurysm surgery: technique and results. AB - The use of temporary clipping has become an established tool in the armamentarium of the aneurysm surgeon. Our experience with 62 consecutive patients is presented, detailing operative protocols and results. Twenty-two had unruptured aneurysms (35%), 15 were grade I (24%), 16 grade II (25%), five grade III (8%), and four grade IV (7%). The aneurysms were mainly located in the middle cerebral artery (29 patients) and the anterior communicating artery (13 patients). Eleven of our 62 patients (17%) developed a new, persistent postoperative deficit. However, in only one case (2%) was temporary clipping felt to be implicated in the development of the deficit. In three other patients (5%), the effect of temporary clipping, although unlikely, could not be excluded. Overall, 92% of our patients with temporary clipping had good to excellent outcome, with 3% mortality and 5% morbidity. We believe that temporary clipping is a safe procedure that contributes significantly to a better outcome. PMID- 1891761 TI - Cerebral vasospasm in elderly patients with ruptured intracranial aneurysms. AB - Cerebral vasospasm in elderly patients who were operated on the acute stage after subarachnoid hemorrhage was studied under strict criteria. The 138 patients were classified into three age groups: 59 years or younger (group A: 73 cases), 60 to 69 years (group B: 37 cases), and 70 years or older (group C: 28 cases). Severity of both the subarachnoid hemorrhages on computed tomography scan and the angiographic vasospasms was graded. The angiographic vasospasms were analyzed at the internal carotid artery, M1 segments of the middle cerebral artery, and A2 segments of the anterior cerebral. In all the relationships among the subarachnoid hemorrhage grades, the Hounsfield numbers, and the operative approaches to the angiographic vasospasm grade, there was a tendency for the angiographic vasospasm grades to be lower with increasing age in both the internal carotid artery and the M1 segment of the middle cerebral artery. This tendency was more apparent in the larger vessels, that is, the internal carotid arteries. Close correlations of the angiographic vasospasm grades to the incidences of symptomatic vasospasm and to low-density area on computed tomography scan were found in both the M1 and A2 territories in the three groups. However, there were no significant differences among the three groups in the incidences of symptomatic vasospasm and low-density area on computed tomography scan. Regarding the surgical outcome, the older the patients, the higher were the mortality rates: 8% in group A, 11% in group B, and 25% in group C.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1891763 TI - Effect of heparin derived fractions on the proliferation and protein synthesis of cells in culture. AB - We investigated the effect of sulfated oligosaccharides derived from depolymerization of heparin on the proliferation and protein synthesis of smooth muscle cells (SMC), hamster kidney (BHK-21) and lung (V-79) fibroblasts, rat hepatoma cells (FAO) and human promyelocytes (HL-60). BHK-21 and FAO showed the highest sensitivity to heparin; V-79 and HL-60 cells were completely resistant. LMWH (Low Molecular Weight Heparin) (MW 4.5 kD) was as effective as unfractionated heparin in reducing cell proliferation. The oligo-derivative 381/1 (MW 2 kD) was effective only on FAO and BHK-21 cells; oligo-derivative 381/2 (MW 1KD) had a negligible effect. The anti-proliferative effect was associated with an increased secretion of some protein classes. This effect was not present in heparin-resistant cells. In conclusion when the molecular size of heparin derivative is reduced below 2 kD (i.e. the size of a hexasaccharide) the anti proliferative activity decreases dramatically. PMID- 1891762 TI - Follow-up study of unruptured aneurysms arising from the C3 and C4 segments of the internal carotid artery. AB - A follow-up study of unruptured aneurysms arising from the C3 and C4 segments of the internal carotid artery was performed. During the 10-year period from 1979 to 1989, there were 22 patients with 24 aneurysms arising from the C3 or C4 segment of the internal carotid artery. All 24 aneurysms were unruptured. They represented 3% of all intracranial aneurysms and 11% of all internal carotid artery aneurysms diagnosed at the hospital during the 10-year period. Eighteen patients were women and 4 were men. Their ages ranged from 34 to 82 years (mean 63.3 years). Of the 22 patients, 12 (55%) had multiple aneurysms. A follow-up study without treatment was made in 15 of the 22 patients who had a total of 16 unruptured aneurysms arising from the C3 or C4 segment of the internal carotid artery. This study excluded 7 of the 22 patients with a total of eight aneurysms because of operation or death soon after diagnosis. The average maximal dimension of the 16 aneurysms was 5 mm, with a range of 2-17 mm. Follow-up periods varied from 11 months to 10.5 years, with an average of 4.7 years. During this period, none of the 16 aneurysms ruptured, and they remained asymptomatic, except for one aneurysm that had been discovered as a result of the cavernous sinus syndrome. Some surgeons are now attempting direct operations on intracavernous carotid artery aneurysms, even if the aneurysms are unruptured and relatively small.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1891765 TI - Correlation of aggregometry responses to changes in light transmission through platelet packs. AB - The transmission of light through 22 platelet packs was monitored during storage with a specially designed apparatus in order to estimate the quality of the platelet concentrates without risking contamination. The changes in light transmission during a 7 day storage period were compared with other properties of platelets upon day 1 and day 7, namely aggregometry responses (to collagen, ADP, and calcium ionophore A23187), platelet factor 4 release, lactate dehydrogenase extracellular activity and pH. On day 7 additional aggregometry tests were carried out with pairs of activators (collagen + ADP, collagen + A23187, collagen + epinephrine, and collagen + arachidonic acid). The 8 concentrates judged as being inferior in quality by the optical apparatus also, with 1 exception, showed inferior quality as assessed from aggregometry responses and/or biochemical analyses. PMID- 1891764 TI - A colourimetric enzyme-linked sandwich assay for the detection of human platelets bound to a fibrinogen-coated surface. AB - A colourimetric enzyme-linked sandwich assay has been developed to investigate the binding of human platelets to fibrinogen. The presence of platelets bound to fibrinogen-coated plastic can easily be detected and quantitated. Platelets treated with chymotrypsin to expose the fibrinogen receptor, are fixed with paraformaldehyde, and stored frozen. The detection sandwich consists of a mouse monoclonal antibody directed against the human platelet CD9 antigen, and a rabbit anti-mouse immunoglobulin conjugated to the enzyme alkaline phosphatase. The cleavage of the phosphatase substrate p-nitrophenyl phosphate can be monitored colourimetrically. The data presented provide evidence that this method is capable of detecting platelet-fibrinogen binding in a physiologically relevant manner. The binding is inhibited by EDTA or excess fibrinogen. The fibrinogen alpha and gamma chain peptides, RGDS and LGGAKQAGDV, and the snake venom echistatin are also inhibitory with IC50 values of 135 microM, 1.8 mM and 100 nM respectively. PMID- 1891766 TI - Inhibitory effects of activated protein C and heparin on thrombotic arterial occlusion in rat mesenteric arteries. AB - Effects of human activated protein C (APC) and heparin on thrombus formation were examined using small mesenteric arteries of rats and video-recording system attached to a microscope. To induce thrombosis we damaged the vessel wall over a short segment by compression and exposed the damaged media to the blood stream. Platelet-rich thrombus enlarged gradually at the damaged site, occluded the vascular lumen for a short period and then flowed away. Such thrombus formation was observed several times after a compression damage. An intravenous administration of APC significantly decreased the total occlusion time from 6.4 +/- 0.7 min at control to 2.2 +/- 0.4 min at 0.9 mg/kg given over 1 min (mean +/- SEM, n = 6, p less than 0.01), and from 6.5 +/- 1.0 min to 1.0 +/- 0.3 min at 3.0 mg/kg (n = 6, p less than 0.01). An intravenous heparin (300 and 1000 U/kg) also decreased the total occlusion time significantly from 6.2 +/- 0.8 to 2.2 +/- 0.8 min (n = 6, p less than 0.05) and from 5.4 +/- 0.8 to 0.8 +/- 0.7 min (n = 6, p less than 0.01), respectively. APC prolonged APTT from 11 +/- 1 sec (n = 5) at control to 50 +/- 5 sec (n = 5) at 0.9 mg/kg and to 87 +/- 8 sec (n = 5) at 3.0 mg/kg, while heparin prolonged APTT to more than 120 sec in all 5 rats at both doses. APTT prolongation by APC was significantly attenuated by inhibiting its residual activity in the plasma samples using monoclonal antibody.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1891767 TI - Analysis of a variant form of platelet glycoprotein (GP) IIb: a second patient with abnormal molecular weight GPIIb. AB - In 1988, we reported a thrombasthenic patient whose platelets contained an abnormal molecular weight GPIIb (Blood, 71, 915, 1988). Here we describe another patient whose platelets contain a variant GPIIb with properties similar to the previously reported abnormal GPIIb. This patient has a small amount of the abnormal GPIIb and was suggested to be a heterozygote characterized by deficient and abnormal GPIIb genes. The abnormal GPIIb was suggested to be related to the precursor form of GPIIb because the molecular weights of both proteins are the same. The abnormal GPIIb may lack a peptide region around the cleavage site of the two chains, as suggested from its lack of reactivity towards antibodies against these epitopes. PMID- 1891768 TI - Human exposure to 3-carene by inhalation: toxicokinetics, effects on pulmonary function and occurrence of irritative and CNS symptoms. AB - Terpenes, especially 3-carene, may irritate the skin and mucous membranes and prolonged exposure may result in allergic contact dermatitis or chronic lung function impairment. The toxicokinetics of 3-carene were studied in human volunteers exposed by inhalation (2 hr 50 W) in an exposure chamber on three occasions. The exposure concentrations were approximately 10, 225, and 450 mg/m3 3-carene. The relative pulmonary uptake was high, approximately 70% for the higher exposure levels. Total uptake increased linearly with increasing exposure. The blood clearance of 3-carene observed in this study, 0.9 liter.kg-1.hr-1, indicates that 3-carene is fairly readily metabolized. About 3% of the total uptake was eliminated unchanged via the lungs while less than 0.001% was eliminated in the urine after the end of exposure. A long half time in blood was observed in the terminal phase which indicates a high affinity to adipose tissues. A statistically significant divergence between ratings of irritation during the high exposure level and during the medium and control levels was observed. The difference in airway resistance after exposure to a high concentration of 3-carene compared to control level was not significant (P = 0.02). PMID- 1891769 TI - Lipid peroxidation and irreversible cell damage: synergism between carbon tetrachloride and 1,2-dibromoethane in isolated rat hepatocytes. AB - The combination of 1,2-dibromoethane (DBE) with carbon tetrachloride (CCl4) in the isolated rat hepatocyte model produces a significant potentiation of both lipid peroxidation and plasma membrane damage induced by the latter compound. The increase in malondialdehyde production precedes the hepatocyte damage, evaluated in terms both of lactate dehydrogenase leakage and trypan blue exclusion. When hepatocytes are isolated from vitamin E pretreated rats, both the prooxidant and the cytotoxic effects of CCl4 are prevented. Also the synergism between CCl4 and DBE on lipid peroxidation disappears completely while that on cell damage is strongly reduced. The increased lipid peroxidation appears to be one of the mechanisms of the observed synergism between CCl4 and DBE on hepatocyte damage. Regarding the antioxidant status of the hepatocyte challenged with CCl4 and DBE, an early and significant consumption of vitamin E is observed only in the presence of the mixture of these xenobiotics. Total nonprotein thiol content is not significantly modified by CCl4 poisoning while DBE, alone and in association with CCl4, markedly decreases it. Vitamin E supplementation does not prevent but moderately delays total nonprotein thiol depletion due to DBE or to the mixture. Finally, glutathione transferase activity is significantly reduced by CCl4 treatment and not by DBE, and vitamin E supplementation totally prevents such inhibition. The increased prooxidant effect of CCl4 plus DBE compared to CCl4 alone seems related to the shift in DBE metabolism consequent to the CCl4 dependent inactivation of glutathione transferase. PMID- 1891770 TI - Studies of inspiratory airflow patterns in the nasal passages of the F344 rat and rhesus monkey using nasal molds: relevance to formaldehyde toxicity. AB - For highly water soluble and reactive gases, such as formaldehyde, the reported distribution of nasal lesions in rats and rhesus monkeys following inhalation exposure may be attributable, at least in part, to regional gas uptake patterns that are a consequence of nasal airflow characteristics. Inspiratory nasal airflow was studied at flow rates across the physiologic range using a unidirectional dynamically similar water-dye siphon system in clear acrylic molds of the nasal airways of F344 rats and rhesus monkeys. In both species there were complex and inspiratory flow streams, exhibiting regions of simple laminar, complex secondary (vortices, eddies, swirling), and turbulent flows, with only minor effects of the volumetric flow rates studied on these flow patterns. There was a precise association between points of dye intake at the nostril with complex but generally coherent streaklines throughout the nose, indicating the potential for sensitive dependence of nasal airflow on nostril geometry. On the basis of these studies, a classification for the major airways (meatuses) in the nasal passages of rats and rhesus monkeys was proposed. The spiral shape of the anterior nasal airway of the rat was considered to play an important role in local mixing of inspired airstreams. In the rhesus monkey, the complex geometry of the nasal vestibule contributed to the formation of secondary flows and turbulence in the anterior nose, which represents a potentially important difference between rheusus monkeys and humans. There was a good correlation between routes of flow, regional secondary flows, turbulence, and impaction of airstreams on the airway wall, with the reported distribution of formaldehyde induced nasal lesions in rats and rhesus monkeys. These studies support the proposal that nasal airflow patterns play an important role in the distribution of lesions induced by formaldehyde. PMID- 1891771 TI - A comparative study of the influence of vicinal dithiols and a dithiocarbamate on the biliary excretion of cadmium in rat. AB - The effect of two vicinal dithiols, 2,3-dimercaptopropan-1-ol (BAL) and N-(2,3 dimercaptopropyl)phthalamidic acid (DMPA), and a dithiocarbamate, sodium N-(4 methoxybenzyl)-D-glucamine dithiocarbamate (MeOBGDTC), on the biliary excretion of cadmium was examined in rats. Tissue cadmium levels were also determined following the measurements of biliary excretion of cadmium. At 30 min after the injection of CdCl2.2.5H2O (1 mg/kg, iv) each rat was given 400 mumol/kg ip of one of the compounds, BAL, DMPA or MeOBGDTC. While all the compounds increased the biliary excretion of cadmium, the most effective was MeOBGDTC, whose administration resulted in a 580% increase in biliary cadmium content. The effectiveness of the MeOBGDTC may be due to the presence of both nonpolar and nonionizing polar groups attached to nitrogen. MeOBGDTC was able to mobilize cadmium to the bile even after the occurrence of the synthesis of metallothionein and the incorporation of the cadmium into it. An attempt was also made to determine the chemical nature of the Cd-MeOBGDTC complex present in the bile by comparing a newly synthesized authentic sample of Cd(MeOBGDTC)2 complex with the hot dioxane extract of the freeze-dried bile samples using thin-layer chromatography and proton NMR. The results suggested that cadmium excreted in the bile in part, is complexed to MeOBGDTC and glutathione. PMID- 1891772 TI - Effect of sodium dichromate on carbohydrate metabolism. AB - Subcutaneous injection of sodium dichromate into male Sprague-Dawley rats immediately produced a variety of metabolic changes in a dose-dependent manner. Serum lactate and glucose were significantly increased after dichromate treatment, reaching maximum levels at 15 and 30 min, respectively. Then, the toxicity progressively diminished. In contrast, a steady increase in blood urea nitrogen (BUN) concentration was caused by dichromate, reaching maximum levels at 60 min after the administration; elevated BUN levels were sustained for several hours thereafter. Unlike KCN (5 mg/kg, ip) and As2O3 (5 mg/kg, ip), dichromate rapidly decreased serum insulin within 15 min after intoxication in doses of 20 and 40 mg/kg; hypoinsulinemia lasted 60 min. However, insulin levels returned to the normal range at 120 min after treatment. Dichromate-induced metabolic disturbance was also observed in the 24 hr-fasted rats, the response of which was similar to normal rats except for later hyperglycemia. In both cases, the duration time was short (30 to 60 min). Adrenalectomy and insulin pretreatment had no effect on dichromate-induced hyperglycemia. These results suggest that dichromate-induced metabolic disturbance results from the concomitant effects of a sudden decrease in serum insulin level and its direct inhibitory effect on carbohydrate metabolism. In addition, the characteristic biphasic pattern of metabolic disturbance might be related to metabolic fate of dichromate in vivo. PMID- 1891773 TI - Cytotoxicity of dibasic esters (DBE) metabolites in rat nasal explants. AB - Dibasic esters (DBE) is a solvent mixture of dimethyl adipate, dimethyl glutarate, and dimethyl succinate which causes a selective degeneration of the nasal olfactory epithelium in rats following a 90-day inhalation exposure. In short-term cultures of rat nasal explants, it has been demonstrated that DBE cytotoxicity is due to a carboxylesterase-mediated activation. In the present study, the putative toxic metabolites of DBE, the monomethyl esters and the dicarboxylic acids, were evaluated in the nasal explant system at concentrations ranging from 10 to 50 mM. Monomethyl adipate (MMA), monomethyl glutarate (MMG), and monomethyl succinate (MMS) induced increases in nasal explant acid phosphatase release, a biochemical index of cytotoxicity. The nasal explant mediated metabolism of MMA and MMG to their corresponding diacids paralleled the increases in acid phosphatase release. A carboxylesterase inhibitor, bis(p nitrophenyl)phosphate (BNPP), inhibited both the cytotoxicity and the hydrolysis of MMA and MMG in the nasal explant system. The metabolism and cytotoxicity of MMS was not attenuated as effectively by BNPP pretreatment. Adipate, glutarate, and succinate induced concentration-related increases in cytotoxicity in the nasal explant system. These dicarboxylic acids were neither metabolized nor utilized significantly by the nasal explants. Diacid-induced cytotoxicity was not attenuated by BNPP pretreatment. This study further established the utility of the nasal explant system for evaluating cytotoxicity of organic esters in vitro. It was established that both the monomethyl ester and diacid metabolites are cytotoxic in rat nasal explants. Finally, it was concluded that although both the monomethyl esters and the diacids contribute to the cytotoxic potential of DBE in vitro, it is critical to establish if one or both of these are formed in vivo in order to identify the ultimate toxic metabolite of DBE. PMID- 1891774 TI - In vivo studies on rhodanese encapsulation in mouse carrier erythrocytes. AB - Resealed erythrocytes containing sodium thiosulfate and rhodanese (CRBC) are being employed as a new approach in the antagonism of cyanide intoxication. In earlier in vitro studies, the behavior of red blood cells containing rhodanese and sodium thiosulfate was investigated with regard to their properties and their capability of metabolizing cyanide to thiocyanate. The present studies are concerned with the properties of these rhodanese-containing carrier erythrocytes in the intact animal. These carrier erythrocytes were administered intravenously and the survival of the encapsulated enzyme was compared with the administration (iv) of free exogenous enzyme. Also, the amount of leakage of the encapsulated rhodanese from the red blood cell was determined. The survival of the carrier red blood cell. prepared by hypotonic dialysis, was found to be characterized by a biphasic curve. There was an initial rapid loss of approximately 40 to 50% of the carrier cells with a t1/2 = 2.5 hr. Subsequently the remaining resealed annealed carrier erythrocytes persisted in the vascular system with a t1/2 = 8.5 days. When free exogenous rhodanese was administered directly into the vascular system, it was rapidly eliminated with a t1/2 = 53 min. Red blood cells containing sodium thiosulfate and rhodanese apparently are effective in vivo in the biotransformation of cyanide. In animals pretreated with encapsulated rhodanese and sodium thiosulfate, blood cyanide concentrations are appreciably decreased with a concomitant increase in thiocyanate ion, a metabolite of cyanide. When erythrocytes, which contained no rhodanese or sodium thiosulfate, were subjected to hypotonic dialysis, cyanide was not metabolized to any appreciable extent. Furthermore, carrier erythrocytes containing rhodanese and sodium thiosulfate were found to increase the protection against the lethal effects of cyanide by approximately twofold. The ability of these carrier erythrocytes alone to metabolize cyanide and to antagonize the lethal effects of cyanide reflects the potential of this new antidotal approach in the antagonism of chemical toxicants. PMID- 1891776 TI - Physiological pharmacokinetic modeling of inhaled trichloroethylene in rats. AB - The pharmacokinetics of trichloroethylene (TCE) was characterized during and following inhalation exposures of male Sprague-Dawley rats. The blood and exhaled breath TCE time-course data were used to formulate and assess the accuracy of predictions of a physiologically based pharmacokinetic (PB-PK) model for TCE inhalation. Fifty or 500 ppm of TCE was inhaled by unanesthetized rats of 325-375 g for 2 hr through a miniaturized one-way breathing valve. Repetitive samples of the inhaled and exhaled breath streams, as well as arterial blood, were collected concurrently during and for 3 hr following the exposures and analyzed for TCE by headspace gas chromatography. Respiratory rates and volumes were continuously monitored and used in conjunction with the pharmacokinetic data to delineate uptake and elimination profiles. Levels of TCE in the exhaled breath attained near steady-state soon after the beginning of exposures, and were then directly proportional to the inhaled concentration. Exhaled breath levels of TCE in rats were similar in magnitude to values previously published for TCE inhalation exposures of humans. Levels of TCE in the blood of the 50 ppm-exposed animals also rapidly approached near steady-state, but blood levels in the 500 ppm exposed animals rose progressively, reaching concentrations 25- to 30-fold higher than in the 50 ppm group during the second hour of exposure. The 10-fold increase in inhaled concentration resulted in an 8.7-fold increase in cumulative uptake, or total absorbed dose. These findings of nonlinearity indicate that metabolic saturation ensued during the 500 ppm exposure. The PB-PK model was characterized as blood flow-limited with TCE eliminated unchanged in the exhaled breath and by saturable liver metabolism. The uptake and elimination profiles were accurately simulated by the PB-PK model for both the 50 and 500 ppm TCE exposure levels. Such a model may be quite useful in risk assessments in predicting internal (i.e., systemically absorbed) doses of TCE and other volatile organics under a variety of exposure scenarios. PMID- 1891775 TI - Metabolic effects of pivalate in isolated rat hepatocytes. AB - Pivalate (trimethylacetic acid) administration in humans or rat has been reported to cause metabolic changes and increased urinary carnitine excretion secondary to pivaloylcarnitine generation. As pivaloylcarnitine formation is dependent on intracellular activation of pivalate, the effects of pivalate on cellular coenzyme A and acyl-CoA contents and oxidative metabolism were defined using isolated rat hepatocytes. During incubations with pivalate (1.0 mM), hepatocyte coenzyme A content fell to less than 0.05 nmol/10(6) cells (vs 0.97 nmol/10(6) cells in the absence of pivalate) as pivaloyl-CoA accumulated. Pivalate (5 mM) inhibited 14CO2 generation from 10 mM [1-14C]pyruvate by 34%, but had no effect on 0.8 mM [1-14C]palmitate oxidation. Pivaloyl-CoA was a substrate for hepatocyte carnitine acyltransferase activity, but supported acylcarnitine formation at rates only 10-20% of those observed with equimolar acetyl-CoA or isovaleryl-CoA as substrates. Thus, hepatocytes activate pivalate to pivaloyl-CoA, which can then be used as a substrate for pivaloylcarnitine formation. The sequestration of hepatocyte coenzyme A as pivaloyl-CoA is associated with inhibition of pyruvate oxidation. As with other organic carboxylic acids, activation of pivalate to the coenzyme A thioester is an important aspect in the biochemical toxicology of the compound. PMID- 1891777 TI - Anticarcinogenic effects of cadmium in B6C3F1 mouse liver and lung. AB - The B6C3F1 mouse liver has been widely used for the evaluation of carcinogenic or tumor promoting efficacy of various organic compounds, although little is known about the actions of metallic carcinogens in this system. Thus, the ability of cadmium to initiate or promote tumors in B6C3F1 mouse liver was studied. In promotion studies, diethylnitrosamine (DEN; 90 mg/kg, ip) was given as an initiator to 5-week-old mice followed 2 weeks later by 500 or 1000 ppm of cadmium in drinking water for 50 weeks. DEN caused an elevation of liver tumor incidence (13 tumor bearing mice/45 total) over control (1/48) which was prevented by cadmium (DEN + 500 ppm cadmium, 3/42; DEN + 1000 cadmium, 0/47). Cadmium alone did not further reduce the very low spontaneous liver and lung tumor incidence at approximately 1 year of age. DEN-induced lung tumor incidence (15/45) was also reduced by cadmium (DEN + 500 ppm cadmium, 11/42; DEN + 1000 ppm cadmium, 1/47) to control levels (0/48). In initiation studies, cadmium (20 or 22.5 mumol/kg, sc) was given to 5-week-old mice (n = 30-60) 2 weeks before an established promoting regimen of sodium barbital (BB) in drinking water at 500 ppm level was begun. Barbital in drinking water was given continuously for up to 92 weeks. Such cadmium doses caused acute, focal hepatic necrosis. Mice treated with BB and killed at 97 weeks of age showed an elevation of liver tumor multiplicity (7.44 tumors/liver) over control (2.24) that was prevented by cadmium in a dose-related manner (20 mumol/kg cadmium + BB, 3.93; 22.5 mumol/kg cadmium + BB, 1.87). Cadmium alone given by injection also reduced spontaneous liver tumor multiplicity. These results indicate that cadmium inhibits tumor formation in the B6C3F1 mouse liver initiation/promotion system regardless of route of exposure or sequence of administration. The possibility exists that cadmium has a specific toxicity toward previously initiated cells within liver and lung. PMID- 1891778 TI - Increase in metallothionein produced by chemicals that induce oxidative stress. AB - Metallothionein (MT) is a low-molecular-weight protein with a high cysteine content that has been proposed to play a role in protecting against oxidative stress. For example, MT has been shown to be a scavenger of hydroxyl radicals in vitro, and cells with high levels of MT are resistant to radiation. However, it is not known if compounds that cause oxidative stress affect MT levels. Therefore, mice were injected subcutaneously with 11 chemicals (t-butyl hydroperoxide, paraquat, diquat, menadione, metronidazole, adriamycin, 3 methylindole, cisplatin, diamide, diethyl maleate, and phorone) that produce oxidative stress by four main mechanisms. MT was quantitated in the cytosol of major organs (liver, pancreas, spleen, kidney, intestine, heart, and lung) by the Cd/hemoglobin radioassay 24 hr after administration of the chemicals. All agents significantly increased MT levels in at least one organ. Liver was the most responsive to these agents in that all 11 chemicals increased MT concentrations in liver, with diethyl maleate, paraquat, and diamide producing 20- to 30-fold increases. Pancreas and kidney were the next most responsive organs to these chemicals. The organ least responsive to these agents was the heart, as only 3 compounds caused significant increases in MT concentrations in heart. Diethyl maleate and diquat were the most general inducers of MT in that they increased MT in six of the seven organs examined. No treatment resulted in a significant decrease in MT concentration in any organ. In conclusion, chemicals that produce oxidative stress by one of four distinct mechanisms are very effective at increasing MT concentrations in a variety of organs. This suggests that MT might be involved in protecting against oxidative stress. PMID- 1891779 TI - 2,4-Dichlorophenoxyacetic acid effects on polyamine biosynthesis. AB - 2,4-Dichlorophenoxyacetic acid (2,4-D) is a herbicide extensively used in agriculture. It was considered of interest to study its toxicity on animal cells. We had previously determined that 1 mM 2,4-D can inhibit cell growth, DNA and protein synthesis of cultured Chinese hamster ovary cells (CHO) with cell accumulation in the G1/S interphase of the cell cycle. The present work examined the effects of 2,4-D on polyamine biosynthesis. The results suggest some possible mechanism of the herbicide's toxic effects on animal cells. PMID- 1891780 TI - Dose-dependent reversal of acute murine colchicine poisoning by goat colchicine specific Fab fragments. AB - The use of colchicine-specific Fab fragments is of interest in human poisoning. In the present study, we show the efficacy of Fab fragments in reversing colchicine toxicity in mice. High affinity antibodies (Ka = 2 x 10(10) M-1) against colchicine were raised in goats; Fab fragments were purified by DEAE chromatography after papain hydrolysis of IgG. Mice were intoxicated with a 100% lethal colchicine dose (3.8 mg/kg). When a half molar dose (M/2) of Fab fragments in relation to the colchicine dose was intravenously and intraperitoneally administered 90 min after colchicine infusion using a multiple dosage schedule, 80% of the Fab-treated mice survived compared to the control group which did not receive Fab fragments (P less than 0.01). Using a M/4 and M/8 dose of Fab fragments, the mortality was respectively 50% and 80%. The dose-effect relationship was linear (r = 0.99). Delayed administration of a M/2 dose of Fab fragments 6 h after colchicine administration resulted in 50% survival (P less than 0.01). Body temperature and body weight were selective markers of the severity of the intoxication. In the control group, a marked decrease of body temperature was observed following the first few hours after the intoxication ( 21% compared to basal value 48 h after colchicine). In the Fab-treated group, the decrease was inversely related to the Fab fragment dose. Body temperature returned to the basal values 7 days after intoxication. A progressive decrease in body weight was concomitantly observed in intoxicated mice until death, while values returned to baseline 9 days after colchicine in surviving Fab-treated mice. PMID- 1891782 TI - Comparative effects of N,N-disubstituted dithiocarbamates on excretion and distribution of cadmium in mice. AB - Sodium N-benzyl-D-glucamine dithiocarbamate (BGD), sodium N-p-hydroxymethylbenzyl D-glucamine dithiocarbamate (HBGD), sodium N-p-carboxybenzyl-D-glucamine dithiocarbamate (CBGD) and sodium N-p-methoxybenzyl-D-glucamine dithiocarbamate (MeOBGD) were evaluated for their efficacy in the distribution and excretion of cadmium in mice exposed to cadmium. Mice were injected i.p. with 109CdCl2 (1 mg Cd/kg and 74 kBq of 109Cd/animal) and 30 min or 24 h later, they were injected with chelating agents (400 mumol/kg). At 30 min after treatment with cadmium, these chelating agents all significantly enhanced the biliary excretion of cadmium, and HBGD and CBGD significantly increased the urinary excretion of the metal. At 24 h after cadmium injection, BGD, HBGD, and MeOBGD significantly increased the biliary excretion of cadmium and HBGD was the most effective on the biliary excretion of the metal. These chelating agents were effective in mobilizing cadmium from the liver at 30 min after cadmium treatment. At 24 h after cadmium treatment, HBGD and MeOBGD effectively depressed cadmium content in the liver and only HBGD among these chelating agents significantly reduced the cadmium content in the kidney. In another experiment, mice were injected i.p. with 109CdCl2 and three days later, they were injected with chelating agents every other day for 2 weeks. HBGD was the most effective on the fecal and urinary excretions of cadmium. The hepatic cadmium content was decreased after HBGD or MeOBGD injection. The injection of HBGD caused a much greater decrease in renal cadmium content than did BGD, CBGD, or MeOBGD. The results of this study indicated that the injection of HBGD to mice pretreated with cadmium can remove cadmium from the body, mainly through fecal excretion, without redistribution of cadmium to other tissues such as the brain, testes, and heart, more effectively than that of BGD, CBGD, or MeOBGD. PMID- 1891781 TI - Heated linoleic acid anilide: toxicity and relevance to toxic oil syndrome. AB - The present study was undertaken to investigate toxic potentials of linoleic acid anilide (LAA) and heated linoleic acid anilide (HLAA) and their possible role in the etiology of toxic oil syndrome (TOS). Male Sprague-Dawley rats were given 250 mg/kg of LAA or HLAA in mineral oil through gavage, on alternate days for 2 weeks (total 7 doses). Control rats received an equal volume of vehicle only. The animals were sacrificed at day 1, 7 and 28 following the last dose. Ratio of organ weight/body weight showed a significant increase in lung in LAA group at day 7 while spleen showed remarkable increases in both treatment groups at day 1 and 7. On the other hand, this ratio showed decreases in case of liver, brain and heart at some time points. Among blood parameters, red cell counts and hemoglobin content decreased at day 1 in both LAA and HLAA treated groups, while platelet counts showed an increase. Serum LDH, GOT and GPT activities significantly decreased at day 1 and 7 in both LAA and HLAA treated groups, however, these changes were more prominent in the HLAA treated group. Interestingly, at day 28, these serum enzyme levels recovered to control levels. Both LAA and HLAA treated groups showed a decrease in serum IgM levels at day 1, however, at day 7 only the LAA group showed a significant decrease. IgA levels significantly increased in both groups at all the time points studied and were more pronounced in the HLAA treated group. Similarly, IgG levels also showed increases in both the groups. In addition to serum immunoglobulin changes, alterations in the lymphocyte subpopulations were also observed. While T-cell population decreased, B-cell population remained unchanged. Among T-cell subsets, T-helper cells did not show any change while T-suppressor cells decreased significantly at day 1 in the LAA group and at day 1 and 7 in the HLAA group, but regained control levels at day 28. The biochemical and immunological alterations observed in this study as a result of LAA and HLAA exposure and more so by HLAA further support that the fatty acid anilides may play a role in the etiology of TOS. PMID- 1891783 TI - Rat liver microsomal ring- and S-oxidation of thiaarenes with central or peripheral thiophene rings. AB - The metabolism of the following thiaarenes has been investigated using liver microsomes of untreated, phenobarbital-, AroclorR- and 5,6-benzoflavone pretreated rats: dibenzothiophene, naphtho[2,1-b]thiophene, benzo[b]naphtho[2,1 b]thiophene, benzo[b]naphtho[1,2-d]thiophene, benzo[b]naphtho-[2,3-d] thiophene, phenanthrol[1,2-b]thiophene, phenanthrol[4,5-bcd] thiophene, triphenyleno[1,12 bcd]-thiophene and dinaphtho[2,1-b:1',2'-d]thiophene. Thiaarenes with a central thiophene ring preferentially undergo S-oxidation and are converted into sulfoxides and sulfones, whereas those with a peripheral thiophene ring are oxidized at the carbocyclic skeleton resulting in the formation of phenols, dihydrodiols and triols. Sulfone formation seems to be inducible by phenobarbital but only little or not by 5,6-benzoflavone treatment. In most cases 5,6 benzoflavone and AroclorR treatment enhanced the rates of ring oxidation. PMID- 1891784 TI - Effect of ethanol on the induction of lung tumours by ethyl carbamate in mice. AB - Groups of 25 female NMRI-mice received daily doses of 0, 18, 36, 90, or 180 mg ethyl carbamate/kg body wt either in water or in 20% ethanol by gavage for 8 weeks. Another 8 weeks later, the animals were sacrificed and lung adenomas were counted. Ethyl carbamate was found to increase the number of lung adenomas per mouse dose-dependently in all dose groups. No significant differences, however, were observed between groups receiving ethyl carbamate in water or in 20% ethanol. Thus, ethanol had no effect on ethyl carbamate induced tumourigenesis. PMID- 1891785 TI - From genes and beans to isotype screens, ABO still flourishes! PMID- 1891786 TI - Do white cells in stored blood components reduce the likelihood of posttransfusion bacterial sepsis? PMID- 1891787 TI - Prevention of platelet alloimmunization. PMID- 1891788 TI - Prevention of alloimmunization in patients with acute leukemia by use of white cell-reduced blood components--a randomized trial. AB - Platelet refractoriness arising from HLA alloimmunization is a serious complication of transfusion therapy. In a prospective randomized trial, white cell (WBC)-reduced blood components were compared to standard platelet and red cell concentrates with respect to alloimmunization, refractoriness, and platelet increments after transfusion. Sixteen of 31 adult acute leukemia patients received only WBC-reduced platelet concentrates (PCs) and red cells (RBCs), with fewer than 10(6) WBCs per unit. Fifteen control patients received standard blood components with a mean of 0.1 x 10(9) (PCs) and 1 x 10(9) (RBCs) WBCs per unit. Platelet loss during cotton-wool filtration averaged 14 percent (range, 3-32%) from fresh PCs and 24 percent (range, 9-62%) from stored PCs. Filtration did not change corrected increments (CI) measured after transfusion of fresh PCs. The Cl 1 hour after filtration of stored PCs diminished by 27 percent, but the difference was smaller after 18 hours, which suggests better survival of WBC reduced platelets. The number of platelet units transfused did not differ in the two groups. No patient in the WBC-reduced group developed permanent platelet refractoriness; transient HLA antibodies of low titer developed in two patients. In the control group, one patient became refractory because of immunization and two developed transient HLA antibodies. It can be concluded that the reduction of WBCs in blood components can effectively prevent alloimmunization. PMID- 1891789 TI - Platelet crossmatching with lymphocytotoxicity test: an effective method in alloimmunized Chinese patients. AB - Fifty-three patients receiving long-term platelet transfusions were regularly screened for platelet-associated antibodies by a platelet suspension immunofluorescence test (PSIFT) and a lymphocytotoxicity test (LCT). Subsequently, 24 patients became alloimmunized; all of their antibodies were of HLA specificity. Eighty-two single-donor platelet transfusions were given, and the clinical responses were considered satisfactory if the 18-hour corrected count increment was 7.5 x 10(3) per microL or higher. In the meantime, 82 pairs of patient sera and donor lymphocytes were crossmatched. Among 63 crossmatched transfusions, 53 (84%) resulted in a satisfactory increment, with a mean (+/- SEM) of 17.71 +/- 1.96 (x 10(3)/microL), and 10 did not result in a satisfactory increment. The increments after 19 unmatched transfusions and 25 random-donor (uncrossmatched) transfusions were 0.7 +/- 0.3 and 2.39 +/- 0.66, respectively. The difference was not significant (p greater than 0.05). The agreement between the LCT results and clinical response was 88 percent. Retrospectively, the corrected count increments showed no significant differences (p greater than 0.05) among three groups of HLA grading: the increments for A/BU/BX, C/D, and random HLA matches were 22.97 +/- 4.07, 15.1 +/- 1.97, and 14.85 +/- 2.04, respectively. These results suggest that platelet crossmatching by LCT is an effective method for use in alloimmunized patients, especially Chinese patients. PMID- 1891790 TI - Design and preliminary evaluation of an expert system for platelet request evaluation. AB - In spite of growing awareness of the potential risks associated with transfusion, the number of platelet units transfused in the United States continues to increase each year. There is a growing interest in ensuring that all transfusions are administered for appropriate reasons. Prospective review of requests for transfusions has been used to accomplish this goal. Although successful in reducing the number of inappropriate transfusions, this review method requires great time commitments by blood bank personnel and physicians. A knowledge-based system (ESPRE) that aids hospital blood bank personnel in the review of requests for platelet transfusions has been developed. The system automatically obtains most of the required patient data via a direct link to the hospital's main laboratory computers. The system generates a printed report that includes a list of patient-specific data, a list of the conditions for which a transfusion would be appropriate for the particular patient (given the clinical condition), and the conclusions drawn by the system. During a preliminary clinical evaluation of ESPRE, 73 randomly selected platelet transfusion requests were evaluated for approval by laboratory personnel and ESPRE. Overall, ESPRE would have approved 71 of the requests and laboratory staff would have approved 72. Forty-four percent of the requests would have been approved for the same reasons given by the staff. There were only three disagreements on final approval between ESPRE and blood bank personnel. This computerized expert system is a promising approach to the prospective review of all platelet transfusions. PMID- 1891791 TI - Antibodies to histo-blood group substances A and B: agglutination titers, Ig class, and IgG subclasses in healthy persons of different age categories. AB - Isotypes and IgG subclasses of ABO antibodies from sera of 235 healthy blood donors were determined by an enzyme-linked immunosorbent assay (ELISA). Synthetic A and B trisaccharide-bovine serum albumin glycoconjugates were used for coating and monoclonal antibodies for the detection of heavy chain isotypes. Hemagglutination titers were determined in addition. Blood donors were between 20 and 67 years old, and at least 10 sera per 10-year age category and ABO blood group were included in this study. Antibody concentrations were expressed as a percentage of an internal standard, and sera with subclass-restricted anti-A and/or anti-B (anti-A/B) responses were used to normalize the ELISA values of IgG subclasses. A good correlation between the sum of the four subclasses and the total anti-A/B IgG values (rs = 0.81 for anti-A and 0.84 for anti-B) was obtained. IgG1 and IgG2 were the most predominant subclasses, but were found in various proportions in different individuals. Donor-to-donor variation exceeded age-related changes for all measured parameters. The correlation of anti-A IgM, IgG, IgA, and their sum with the agglutination titers was significant and revealed rs values of 0.70, 0.65, 0.65, and 0.80, respectively. For anti-B as well, the correlation of ELISA values with the agglutination titer was best when all three isotypes were added. We conclude that anti-A/B IgA, together with IgM and IgG, substantially contributes to the agglutination reaction. Potentially autoreactive antibodies were detected in sera of blood groups A, B, and AB. PMID- 1891792 TI - Detection of anti-A in neonatal serum. AB - The thirteenth edition of the standards of the American Association of Blood Banks did not require the use of A1 red cells (RBCs) or an indirect antiglobulin test (IAT) to detect anti-A in neonatal serum, whereas the fourteenth edition mandates both. The present study was conducted to help document the need for these changes. Incomplete expression of the A antigen in neonatal patients can contribute to the accumulation of unabsorbed maternal anti-A that is capable of mediating the immune destruction of transfused adult RBCs. Sera from 50 group A neonatal infants of group O mothers were tested for anti-A by using RBC segments of A1 and A2 units of AS-1 RBCs less than 14 days old and also with A1 reagent RBCs. Of 22 sera in which anti-A was detected by RBCs from the A1 units with an IAT, anti-A was detected by RBCs from the A2 unit in only 1 and by the reagent RBCs in 17. In 19 (86%) of the 22 neonatal patients in whose sera anti-A was detected, the antibody was found only with the use of anti-human globulin in the IAT. It is concluded that testing to detect circulating anti-A in neonatal patients should include an IAT, and that it is preferable to use A1 RBCs for the initial evaluation. PMID- 1891793 TI - A rapid screening test for detection of IgA deficiency. AB - A solid-phase red cell adherence (SPRCA) assay has been developed to screen blood donors for IgA deficiency, and 6117 donor sera have been screened by this method. Eighteen sera were found to be IgA deficient, which represents a frequency of 1 in 340. Seventeen of these sera were retested by passive hemagglutination inhibition, which has a sensitivity of approximately 0.1 mg per dL. Eight sera were confirmed as IgA deficient, and nine were found to contain low levels of IgA (less than 1 mg/dL). The approximate sensitivity of the SPRCA assay is 1 mg per dL. The speed, simplicity, and sensitivity of this assay make it a good alternative to conventional methods of screening. PMID- 1891794 TI - Suitable survival and half-life of red cells after frozen storage in excess of 10 years. AB - To examine the appropriateness of the Food and Drug Administration's 10-year storage time for previously frozen red cells, 24-hour posttransfusion survival studies were performed, and the half-life of 3 units of autologous red cells that had been stored for 13.5, 14, and 17 years, respectively, was measured. The units had acceptable freeze-thaw-wash recovery (83.3-91.4%). When a 51Cr label was used for the previously frozen red cells and a simultaneous 52Cr label for freshly drawn autologous red cells was used as a comparison, it was seen that the previously frozen cells had normal 24-hour posttransfusion survival (75.1-88.4%) as well as normal half-life (23-33.7 days). These findings support further extension of the maximum allowable storage time for previously frozen red cells. PMID- 1891795 TI - Serial immunoreactive erythropoietin levels in autologous blood donors. AB - The variations in plasma erythropoietin (EPO) concentration during preoperative deposit of autologous blood were studied in 12 patients (8 men, 4 women). Four donations were scheduled at weekly intervals. A predonation hemoglobin concentration of 11 g per dL (110 g/L) was required. Hemoglobin concentration decreased from 14.3 +/- 1.1 g per dL (143 +/- 11 g/L) (mean +/- SD) before the first donation to 11.7 +/- 0.7 g per dL (117 +/- 7 g/L) on Day 22 (p less than or equal to 0.0001). Reticulocyte counts increased from a median of 31,800 (range, 4900-95,000) per microL (median, 32 x 10(9)/L [range, 5-95 x 10(9)/L]) to 93,800 (16,800-194,900) per microL (median, 94 x 10(9)/L [range, 17-195 x 10(9)/L]) on Day 28 (p less than or equal to 0.01). Plasma EPO concentration was 17.8 +/- 5.1 mU per mL prior to the first donation and displayed a small and transient peak after each donation. A sustained elevation followed each peak. Although plasma EPO concentration differed significantly from the baseline value after the first donation, only the peak concentrations after the second (35.5 +/- 15.5 mU/mL), third (38.0 +/- 14.5 mU/mL), and fourth (36.1 +/- 11.0 mU/mL) donations exceeded the normal range. The moderate, biphasic increase in plasma EPO concentration and the moderate increase in erythropoiesis suggest two strategies in autologous blood donation that should be investigated with respect to efficiency and safety: 1) more aggressive donation schemes, which reduce donation intervals and/or the minimum hemoglobin concentration and 2) the administration of recombinant human EPO. PMID- 1891796 TI - Intraoperative blood salvage: a review. PMID- 1891797 TI - The i phenotype and congenital cataracts among Chinese in Taiwan. PMID- 1891798 TI - Storage of autologous blood collections. PMID- 1891799 TI - Adipose tissue metabolism can now be directly studied in vivo. PMID- 1891800 TI - Inside a living cell. PMID- 1891801 TI - The calcium-binding proteins. PMID- 1891802 TI - Membrane protein structure prediction: cytochrome b. PMID- 1891803 TI - Carbon metabolism in early amphibian embryos. AB - Xenopus embryos undergoing cleavage utilize amino acids as their main carbon source for metabolism. Glycolysis (from stored glycogen) begins near the onset of gastrulation. Thus, a major transition in the metabolism of the early embryo occurs before morphological differentiation. The enzymology that supports the carbon metabolism of the cleaving amphibian embryo resembles that of many mammalian tumor cells. PMID- 1891804 TI - Semi-synthetic approaches to novel penicillins. AB - The first part of this account of the discovery of penicillin, published in last month's issue of TIBS, concluded with the detection of 6-beta-amino-penicillanic acid (6-APA), the nucleus of the penicillin structure. The exploitation of 6-APA led to the preparation of a range of clinically important semi-synthetic penicillins, which is described in this article. PMID- 1891805 TI - Distribution of vitamin A compounds in bovine eyes after bleaching adaptation. AB - A seasonal increase in the amount of bleached rhodopsin caused, in living animals, by the seasonal increase of the intensity of sunlight in the early morning before the calves are killed, was verified in the bovine eyes subjected to the present study. This was used as a means of assaying distribution and isomer composition of esterified and unesterified retinol in eyes from animals light-adapted to a different extent under environmental conditions. The progressive increase of bleached rhodopsin results in a parallel increase of all trans-retinol in retina and of both all-trans- and 11-cis-retinyl esters in pigment epithelium. Analytical subcellular fractionation of RPE homogenate reveals that retinyl esters accumulate without an exclusive subcellular localization in nuclear, mitochondrial/lysosomal and microsomal fractions. Whatever the amount of bleached rhodopsin, only small and constant amounts of retinyl esters are found in the soluble fraction of RPE, entirely under the all trans configuration. When a considerable portion of rhodopsin is bleached (about 70%), substantial amounts of all-trans-retinol, along with minor amounts of 11 cis-retinol, accumulate in RPE subcellular organelles. The in vitro bleaching of bovine eyes results in a distribution of retinoids between retina and RPE which appears different from that detected in eyes naturally bleached to the same extent. PMID- 1891806 TI - Population study of horizontal cells in live carp retinas using microinjections of horseradish peroxidase. AB - In order to randomly sample horizontal cells (HCs) of carp retina, horseradish peroxidase (HRP) was delivered into axon terminals by means of vitreally inserted micropipettes in live fish. Survival time was extended to several hours to permit label diffusion into HC somata. A function measuring the relative complexity of cell contours was defined in order to help classify HCs according to their morphological types. The histogram of measurement from 313 HCs showed three modes fitting normal distributions. The numbers of cells in each group were 267, 36 and 10, respectively, representing a relative population of 85.3% H1s, 11.5% H2s and 3.2% H3s. It is suggested that cone HC somata are extended in a monolayer constituted by predominant type-H1 with interspersed groups of both type-H2 and type-H3 cells. PMID- 1891807 TI - Light adaptation and frequency transfer properties of cat horizontal cells. AB - The frequency transfer properties of horizontal cells in the cat retina were studied as a function of the mean light intensity level and stimulus contrast. To this end, horizontal cell responses to sinusoidally modulated light stimuli were recorded intracellularly in the optically intact, in vivo eye. The light stimulus consisted of a 3.9 deg dia. spot superimposed on a steady background (8.8 deg dia.). A discrete Fourier analysis was performed in order to describe the amplitude and phase characteristics of the linear response component and in order to specify the nonlinear distortion of the response. The amplitude of the fundamental Fourier component was found to increase linearly with the contrast of the sinusoidal light intensity modulation. Increasing the mean light level while keeping the contrast constant caused a frequency dependent increase in response amplitude. The increase was most pronounced at high temporal frequencies and resulted in a conspicuous increase of the flicker fusion frequency. Steady background illumination caused a reduction of the response amplitudes at the lower temporal frequencies. Responses in the high frequency range, however, were not affected. The phase shifts of the fundamental Fourier components were found to diminish at increasing mean illumination levels. The harmonic distortion of horizontal cell responses to sinewave flicker was studied as a function of stimulus frequency and stimulus contrast. By comparing the data obtained using sinusoidal light intensity modulation with the intensity profiles described in a preceding paper it was investigated to what extent the harmonic distortion can be explained by the nonlinearity expressed in the response vs intensity profiles. PMID- 1891808 TI - Striate cortical contribution to the surface-recorded pattern-reversal VEP in the alert monkey. AB - The striate cortical contribution to the surface pattern-reversal visual evoked potential (VEP) was investigated in awake monkeys during performance of a visual fixation task, by examining laminar profiles of VEP, current source density (CSD) and concomitant multiunit activity (MUA) in Area 17, recorded simultaneously at incremental depths using multicontact electrodes. Stimuli were black/white bar gratings centered on the fixation point. The typical surface pattern-reversal VEP over striate cortex consists of a prominent positivity peaking at 50-70 msec (P60), followed by a large negativity peaking at approx. 80 msec (N80), and then by a late broad positivity, peaking between 120 and 150 msec (P125). P60 is often preceded by a small negativity peaking at 45-55 msec (N50), and on rare occasions a small positivity (P40) is also observed. N50 is generated primarily by current sinks in Lamina 4C. P60 arises from large current sources in the supragranular laminae. N80 and P125 appear to be composite waveforms reflecting complex contributions from local activity and from activity occurring outside of the foveal/immediate parafoveal representation in Area 17. The basic physiologic sequence elicited by patterned stimulation is similar to that elicited by diffuse luminance or by electrical stimulation, but is characterized by more prominent supra- and infragranular activation. It is consistent with the cellular and synaptic anatomy of Area 17: initial activation of the thalamorecipient subdivisions of Lamina 4C, followed by activation of mid/upper Lamina 4 and of supra- and infragranular laminae. Our results suggest the possibility of differentiating synaptic stages and cellular processes reflected in the human VEP, based on homologies with simian VEP components. PMID- 1891810 TI - Spatial frequency tuning of human stereopsis. AB - A masking paradigm was employed to measure the spatial frequency selectivity of channels underlying human stereopsis. Observers viewed spatially filtered (0.4 octave bandwidth) random-dot stereograms in which a disparate bar appeared in either the top or bottom half of the display; superimposed on one RDS half-image was a noise target whose spatial frequency content was varied relative to that of the RDS. A staircase procedure was used to measure the monocular noise energy (and hence the signal-to-noise ratio) at which observers could judge the location of the disparate bar on 71% of trials. Statistical analyses showed that the resulting stereoscopic masking functions could be grouped into two sets, one with peak sensitivity at 3 c/deg and the other with peak sensitivity at 5 c/deg. These two channels were observed for both crossed and uncrossed disparities ranging from coarse to fine. Essentially the same results were obtained with binocular noise and with stereo displays flashed too briefly to be affected by eye movements. Our results are inconsistent with models of stereopsis in which the disparity range to which a channel is sensitive varies with that channel's peak spatial frequency. These data imply that the spatial frequency selectivity of stereopsis differs from the tuning of spatial channels underlying the detection and discrimination of form. PMID- 1891809 TI - Spatial-frequency-tuned attenuation and enhancement of the steady-state VEP by grating adaptation. AB - Steady-state visual evoked potentials (VEPs) were recorded from adults using 10% C fast spatial frequency (SF) sweeps of horizontal gratings under two conditions: (a) after exposure to a 40% C grating of 6 or 4 c/deg, and (b) after exposure to a blank screen equalling the adapting gratings in space-averaged luminance. SF adaptation attenuated VEP amplitude near the adapting SF, but maximum attenuation was displaced from the adapting SF for 6 c/deg adaptation. Small displacements in maximum attenuation would be expected if underlying neural subunits are tuned to a small number of different center SFs. In addition, SF adaptation caused amplitude enhancement 1.0-2.0 octaves below the adapting SF, providing electrophysiological evidence in humans for coinhibitory relationships among neural mechanisms that have been postulated on the basis of analogous psychophysical findings. The results are consistent with coinhibition between SF tuned subunits and between transient and sustained mechanisms. PMID- 1891811 TI - On the coexistence of stereopsis and binocular rivalry. AB - Dichoptically viewed complex texture stereograms with correlated spatial frequency information can yield stable depth perception, implying cooperative interaction between the two eyes. Dichoptically viewed dissimilar texture pairs may yield competition in the form of binocular rivalry. To study whether stereopsis and rivalry can spatially coexist when stimulus conditions for both are present, we had observers dichoptically view spatial frequency filtered random-dot patterns. The left eye viewed one half-image of an RDS; the right eye viewed the superimposition of the other RDS half-image (which when paired alone with the left-eye RDS yielded stereoscopic depth) and a noise target (which on its own engaged in rivalry with the right eye target). Observers judged the quality of depth and the rate of rivalry for these stereo-pairs. When the contrast of the noise component was low, observers experienced stereopsis and stable single vision that included the noise. At intermediate noise contrasts, local regions were seen either in rivalry or in stereoscopic depth, but rivalry and depth were not experienced at the same spatial location simultaneously. At high noise contrasts, the right eye target dominated almost exclusively, with little hint of stereopsis. Essentially the same pattern of results was obtained in forced-choice experiments in which observers judged the direction of stereoscopic tilt from vertical cosine gratings differing slightly in spatial frequency. Considered together, these results are inconsistent with theories positing that rivalry and stereopsis coexist at the same spatial location because they occur within independent, parallel pathways. PMID- 1891812 TI - Interaction of spatial frequency and separation in vernier acuity. AB - There are two general theories which attempt to explain the ability to judge the relative positions of objects in the visual field. The first is the "local-sign" model which assigns location to individual features of the stimulus. The other is the "channel" model involving pooling of responses of overlapping filters having different spatial frequency and orientation tuning. We set out to investigate these using vernier stimuli whose frequency content could be controlled. The stimuli consisted of vertically orientated sinusoidal gratings placed one above the other with a variable separation between them. Thresholds for high frequency gratings increased rapidly with separation while low frequencies were little affected. In addition the cycle width of gratings which could just be distinguished as being in or out of phase and of gratings which gave optimum vernier acuity both increased linearly with separation. Results are discussed in terms of a model based on spatial frequency filters and we suggest that our findings place significant constraints upon a local-sign model. PMID- 1891813 TI - Stimulus-specific mechanisms of visual short-term memory. AB - The retention of spatial information in visual short-term memory was assessed by measuring spatial frequency discrimination thresholds with a two-interval forced choice task varying the time interval between the two gratings to be compared. The memory of spatial frequency information was perfect across 10-sec interstimulus intervals. Presentation of a "memory masker" grating during the interstimulus interval may interfere with short-term memory. This interference depends on the relative spatial frequency of the test and masker gratings, with maximum interference at spatial frequency differences of 1-1.5 octaves and beyond. This range of interference with short-term memory is comparable to the bandwidth of sensory masking or adaptation. A change of the relative orientation of test and masker gratings does not produce interference with spatial frequency discrimination thresholds. These results suggest stimulus-specific interactions at higher-level representations of visual form. PMID- 1891814 TI - Brightness perception and filling-in. AB - Three experiments were performed in which a stimulus with homogeneous color and luminance was masked by a second stimulus containing contours. In the first experiment the target was a large white disk and the mask was a white circle concentric with the disk but of smaller radius. We found that the mask had a large (up to 2 log unit) suppressive effect on the brightness of the target, but only inside the radius of the mask. With monoptic presentation of target and mask, the greatest suppression was observed with an SOA of 50-100 msec. With dichoptic presentation the strongest suppression was obtained with simultaneous stimuli. The second experiment demonstrated that the latest time at which masking was effective was correlated with the distance between the edge of the target stimulus and the contour in the mask. One possible explanation of the results from these two experiments is that the masking contour is interfering with the propagation of a brightness signal from the target's border. In the third experiment gaps were introduced into the masking circle. Surprisingly, even with rather large gaps there was significant suppression of brightness in the center of the target. We have encountered difficulties attempting to account for these findings with known physiological mechanisms such as lateral inhibition. A qualitative explanation of the results that looks promising is a two-component process involving brightness filling-in and smoothing to satisfy fixed boundary conditions at contours. PMID- 1891815 TI - The regulation of eye growth and refractive state: an experimental study of emmetropization. AB - During growth the vertebrate eye achieves a close match between the power of its optics and its axial length with the result that images are focused on the retina without accommodative effort (emmetropia). The possibility that vision is required for the regulation of eye growth was studied experimentally in chicks made myopic or hyperopic by different visual manipulations. After discontinuing these visual manipulations, the eyes returned quickly to emmetropia mainly by adjusting the growth of their vitreous chambers; growth stopped in eyes recovering from myopia and continued in eyes recovering from hyperopia. Because both hyperopic and myopic eyes were already larger than normal controls, the difference in growth indicates that refractive error, rather than eye size per se, guides the eye toward emmetropia. Evidence is also presented for nonvisual shape-related control of eye growth, but this is slow-acting and cannot explain the emmetropization from induced refractive errors. Both the visually guided and shape-related mechanisms work even in eyes with the optic nerve cut, indicating that the two mechanisms are local to the eye. Although the optic-nerve-sectioned eye can sense the sign of a refractive error and initially adjust growth accordingly, it eventually overshoots emmetropia and reverses the sign of the initial refractive error. Whether this is due to loss of feedback from the central nervous system or retinal ganglion cells is unclear. PMID- 1891816 TI - The shift effect can be elicited with both foveal and peripheral masks. AB - Foveal target detection thresholds are elevated by presenting a counterphasing, vertical squarewave grating in the peripheral retina. This psychophysical "shift effect" has been considered to be an analogue of the neurophysiological "periphery effect" first described by McIlwain (1964; Journal of Neurophysiology, 27, 1154-1173). Physiological response properties of cells from the retina and lateral geniculate nucleus of cat and primate visual systems predict that sensitivity thresholds should also be elevated for peripheral targets in the presence of a foveal counterphasing mask. In these experiments, contrast sensitivities for human observers were obtained using a two-interval forced choice procedure for peripheral target sinusoids in the presence of a foveal counterphasing mask. A suppressive shift effect was elicited by the foveal counterphasing squarewave mask, but only for counterphasing peripheral sinusoids. Masking was only obtained at the lowest spatial frequencies for both the peripheral and foveal shift effects. PMID- 1891817 TI - Temporal summation in dark-adapted 10-week old infants. AB - The effect of stimulus duration on the b-wave and psychophysical responses of dark-adapted 10-week-old infants and adult control subjects is reported. Both infant and adult b-wave sensitivities vary with stimulus duration, show summation for brief duration stimuli, critical durations estimated at 88-155 msec, and little variation in sensitivity for longer durations. There are however, substantial differences between the infant and adult psychophysical temporal summation functions. The infant function is described by a straight line, slope about -0.5, across all flash durations while adults show summation at durations less than 100 msec and critical durations of 136 to 151 msec. Adult, but not infant, b-wave integration times and b-wave rise and fall times show duration dependent changes. Thus, both ERG and psychophysical measures demonstrate immaturities in the rod mediated function of the infant retina. PMID- 1891818 TI - Two-dimensional spatial distortions in human strabismic amblyopia. AB - Two-dimensional space perception was measured in the central visual field of amblyopic subjects under special consideration of spatial distortions and spatial uncertainty. The subjects had to construct circles with different radii around a given fixation point. Subjects with deep strabismic amblyopia were showed to exhibit considerable distortion in the amblyopic eye. Each subject exhibited an individual distortion pattern. The dominant eye showed distortions similar to those seen in normal observers. Subjects with mild strabismic amblyopia, strabismic alternators and anisometropic amblyopes did not exhibit any significant spatial distortions. Data from dichoptic localization experiments indicate that anomalous retinal correspondence might contribute to monocular spatial distortions. PMID- 1891819 TI - The existence of a center of gravity effect during reading. AB - Many experiments have shown the existence of a "global effect" during peripheral target fixation tasks: whatever the position of the target in peripheral vision, the eye lands first near the center of gravity of the global peripheral configuration. The present paper investigates whether such an effect might be present during text reading. The experiments reported tested whether the eye's initial landing position in a test word was affected by the presence of other words or stimuli in the peripheral visual field. Results showed that essentially the information present up to seven characters from the beginning of the test word influenced the eye's landing position in the test word. Moreover, the position where the eye landed corresponded to the location of the cortically weighted center of gravity of this critical peripheral configuration. On the basis of these results, new hypotheses were proposed to explain saccade length programming and eye guidance during reading. PMID- 1891820 TI - Discrimination of spatial phase shows a qualitative difference between foveal and peripheral processing. AB - Detection and discrimination of compound grating stimuli were examined in foveal and peripheral vision. At the fovea, stimuli containing two components (spatial frequencies F and 3F) can be discriminated on the basis of their relative spatial phase when the 3F component is at a contrast below its independent detection threshold. This is no longer the case at increasing retinal eccentricity, where phase discrimination thresholds fall off much more steeply than simple detection thresholds. This relative fall-off in discrimination performance is still present for stimuli scaled for the cortical magnification factor, and is not attributable to fading of peripheral images due to the Troxler effect. The results therefore must imply a qualitative change in the processing of phase information between foveal and peripheral vision. PMID- 1891821 TI - Optokinetic torsion: dynamics and relation to circularvection. AB - Continuous records of optokinetic torsion to sinusoidal inputs were obtained using the electromagnetic scleral search-coil technique. We measured the gain and phase lag of optokinetic torsion in response to a spherical visual display rotating steadily at various angular velocities and sinusoidally at frequencies from 0.2 to 2.0 Hz and at amplitudes from 10 to 80 deg. Gain (peak slow-phase eye velocity over stimulus angular velocity) of up to 0.12 were obtained with stimulus frequencies of 0.2 Hz and declined to an average value of about 0.02 at a frequency of 2.0 Hz. Phase lag was virtually zero at a frequency of 0.2 Hz and increased to over 80 deg at 2.0 Hz. The records from the sinusoidal stimuli show very few quick phases. With increasing stimulus amplitudes, the amplitude of the response increased but its gain declined. We found no evidence of torsional after nystagmus nor any relation between the torsional response and reports of vection or sensation of body tilt induced by the rotating display. Torsional optokinetic nystagmus is most suited to compensate for low-amplitude, low-frequency stimulus rotation and normally supplements torsion induced by head tilt. PMID- 1891822 TI - Accurate control of contrast on microcomputer displays. AB - Off-the-shelf microcomputers can now display arbitrary 8-bit images, but accurate control of these images requires dealing with several undesirable properties of real digital to analog converters (DACs) and analog video monitors. The limitations of DACs and video monitors are presented in the form of a model for their calibration and use in vision experiments. Low contrasts can be accurately rendered by summing a small accurate a.c. signal and a large less-accurate d.c. signal (Watson et al., 1986; Behavior Research, Method, Instrument and Computers, 18, 587-594). Exploiting that idea, this note presents an easy-to-build passive resistor network, a video attenuator, that combines the outputs of three 8-bit DACs to render low contrasts with 12-bit accuracy at the display. Measurements confirm the 12-bit accuracy. PMID- 1891823 TI - Systematic distortions of shape from stereopsis. AB - The effectiveness of disparity information in defining 3-D shape was investigated by means of judgements of the shape of cylindrical continuous curved surfaces presented as random dot stereograms. At a close viewing distance, truly circular cylinders appeared elongated; at an intermediate distance, perception was close to veridical; and, at a far distance, cylinders appeared flattened. Indirect measures of scaling distance were calculated from these data. The results strongly suggest that the observed shape distortions are a consequence of scaling horizontal disparities with an incorrect measure of egocentric distance. PMID- 1891824 TI - Dependence of intraocular straylight on pigmentation and light transmission through the ocular wall. AB - The straylight function of the human eye depends on eye color, especially at larger angles of scattering. As a potential cause for this dependence, transmission of light through the ocular wall was measured, using a psychophysical method. For a light-blue eye effective transmission of the iris was 1% for red and 0.2% for green light. Also the eyewall around the iris transmits a significant amount of light. For the dark-brown eyes of pigmented individuals transmission is lower by two orders of magnitude. Although important, transmission proved to be only partly responsible for the pigmentation dependence, the other cause probably being reflection from the fundus. PMID- 1891825 TI - The relative contributions of pre-neural and neural factors to areal summation in the fovea. AB - In order to determine the relative contributions of pre-neural and neural factors to areal summation in the fovea, measurements of Ricco's area were made. These were compared to the results of an ideal-observer analysis which incorporated only pre-neural factors, up to the level of the photoreceptor. The comparison indicated that Ricco's area in the fovea is largely (if not completely) accounted for by pre-neural factors. Thus, our results, in agreement with the recent analysis of contrast sensitivity by Banks, Geisler and Bennett (1987; Vision Research, 27, 1915-1924), are consistent with the hypothesis that a neural pathway exists which consists of units whose center mechanisms sum over only a single cone or a single row of cones. Our results also imply that the quantum efficiency for detection is constant for test areas up to 256 min2, once the effects of the optics and receptor aperture are factored out. PMID- 1891826 TI - Color opponent coding in the visual system of the honeybee. AB - A model is presented for the color vision system of the honeybee, which takes the nonlinear phototransduction process in the photoreceptors into account and assumes linear computations of the excitations of the photoreceptors. The model parameters are derived by a least squares fit of the scale values determined by multidimensional scaling analysis of the results of color choice experiments to the excitation values of two hypothetical spectral antagonistic coding cells. The psychophysical scale values are interpreted physiologically. Furthermore, a color difference formula is presented which is based on the color opponent coding (COC) model. The model explains quantitatively (1) the sensitivity of spectral antagonistic neurons measured by Kien and Menzel (1977; Journal of Comparative Physiology, 113, 17-34, 35-53), (2) the color discrimination function measured by von Helversen (1972; Journal of Comparative Physiology, 80, 439-472). The following predictions are derived from the model: (1) excitation/log (I) curves of the spectral antagonistic neurons; and from the model in conjunction with the color difference formula: (2) intensity dependent color shifts (Bezold-Brucke effect); (3) the intensity dependence of wavelength discrimination. PMID- 1891827 TI - Object spatial frequencies, retinal spatial frequencies, noise, and the efficiency of letter discrimination. AB - To determine which spatial frequencies are most effective for letter identification, and whether this is because letters are objectively more discriminable in these frequency bands or because can utilize the information more efficiently, we studied the 26 upper-case letters of English. Six two-octave wide filters were used to produce spatially filtered letters with 2D-mean frequencies ranging from 0.4 to 20 cycles per letter height. Subjects attempted to identify filtered letters in the presence of identically filtered, added Gaussian noise. The percent of correct letter identifications vs s/n (the root mean-square ratio of signal to noise power) was determined for each band at four viewing distances ranging over 32:1. Object spatial frequency band and s/n determine presence of information in the stimulus; viewing distance determines retinal spatial frequency, and affects only ability to utilize. Viewing distance had no effect upon letter discriminability: object spatial frequency, not retinal spatial frequency, determined discriminability. To determine discrimination efficiency, we compared human discrimination to an ideal discriminator. For our two-octave wide bands, s/n performance of humans and of the ideal detector improved with frequency mainly because linear bandwidth increased as a function of frequency. Relative to the ideal detector, human efficiency was 0 in the lowest frequency bands, reached a maximum of 0.42 at 1.5 cycles per object and dropped to about 0.104 in the highest band. Thus, our subjects best extract upper case letter information from spatial frequencies of 1.5 cycles per object height, and they can extract it with equal efficiency over a 32:1 range of retinal frequencies, from 0.074 to more than 2.3 cycles per degree of visual angle. PMID- 1891828 TI - Elasticity of tissues involved in accommodation. AB - Uniaxial loading of human lens, zonules, ciliary muscle, and choroid shows a nonlinear relationship between stress and deformation of the specimen, and hysteresis on unloading. Spring constants, at 10% elongation, have been calculated for all specimens and for several combinations. Except for zonules they are significantly correlated with age. They will provide a basis for a model of accommodation. The mean force required for 10% elongation of the lens, at mean age 43, is about 22 x greater than for the zonules; and the mean elongation of the zonules is nearly 7 x that of the lens at a load of 0.01 N (approximately 1 g). Ranges of forces and pressures in the accommodated and nonaccommodated eye are estimated. PMID- 1891829 TI - Increase in saccadic peak velocity with increased frequency of saccades in man. AB - Twelve normal subjects (aged 22-80 yr, mean 47 yr) performed three blocks of 20 saccades made to LED targets stepped back and forth. The first and last blocks were performed at a (slow) rate of 0.18 Hz, while the middle block was performed at the faster rate of 1.15 Hz. Mean saccadic amplitude was unaffected by saccade rate, but latency and duration became shorter at the higher frequency. Most interestingly, the peak velocity increased by approx. 6% when saccades were performed at the higher rate. This increase was statistically significant, even after normalization for saccade amplitude. That saccadic frequency may affect saccadic peak velocity must be considered as a potential variable when analysing saccades. PMID- 1891830 TI - Visual resolution limits in human albinism. AB - The effects of the involuntary ocular oscillations on visual resolution was examined in 22 albinos and 11 idiopaths with congenital nystagmus. The idiopaths showed a linear relationship between the proportion of the slow phase spent at low velocities (less than or equal to deg/sec) and the log of the minimum angle of resolution; such that long dwell times were compatible with good resolution. For the albinos there appeared to be a critical duration of low retinal slip velocities above which there was no improvement in acuity. This supports the contention that factors other than the congenital nystagmus limit visual resolution in the albino. PMID- 1891831 TI - Orientation discrimination depends on spatial frequency. AB - Thresholds were measured for discriminating the orientation of sinusoidal gratings of varying spatial frequency, and found to decrease monotonically with increasing spatial frequency. For discrimination of high-contrast (10 times threshold) near-vertical gratings, thresholds ranged from about 1 deg at 0.04 c/deg to 0.5 deg at 0.2 c/deg, after which there was little improvement. At lower contrasts and for discriminations around a mean of 45 deg, thresholds varied more so, and continued to improve until 1 c/deg. The variation of orientation discrimination thresholds with spatial frequency follows a similar trend to the variation in orientation bandwidth of visual units over the same range of spatial frequencies. Thus the present results are consistent with recent "opponent process" models of orientation discrimination, that predict that thresholds to be limited (at least in part) by the maximum slope of orientation selectivity of visual detectors. That thresholds for high contrast vertical gratings did not improve for frequencies higher than 0.2 c/deg implies that orientation bandwidth and noisiness of oriented detectors may not be the sole factor limiting orientation discrimination, and suggests the existence of more central noise sources. PMID- 1891832 TI - A method for estimating the minimum visual stimulus that evokes a behavioural response in the drone, Apis mellifera male. AB - Drones, attracted to an observation site by a scented lure, left the lure to fly directly towards a small object suspended nearby. An object the size of a queen bee was detected at distances up to 2 m. It is estimated that at this maximum distance the object will have decreased the light incident on a single rhabdom by 6%. PMID- 1891833 TI - [Clinical evaluation of middle and low molecular weight substances in the serum]. PMID- 1891834 TI - [Atypical case of lymphogranulomatosis]. PMID- 1891836 TI - [Acute myocardial infarction caused by repeated wasp sting]. PMID- 1891835 TI - [Polyneuropathy in the compression positional syndrome]. PMID- 1891837 TI - [Manpower structure of scientific-research institutes of Ministry of Public Health of Ukrainian SSR and its effectiveness]. PMID- 1891838 TI - [Incidence of various internal diseases among rural population of Zhitomir district]. PMID- 1891839 TI - [Forums of Ukrainian physicians in commemorative emblems]. PMID- 1891840 TI - [Prospects for the therapeutic use of liposomes in the medical practice]. PMID- 1891841 TI - [Manual therapy in the combined treatment of patients with vertebral vestibular dysfunction]. PMID- 1891843 TI - [Epidemiology and prophylaxis of malignant neoplasms]. PMID- 1891842 TI - [Sorption detoxification in the treatment of patients with tuberculosis]. PMID- 1891844 TI - [Chronotropic insufficiency in patients with ischemic heart disease]. AB - A study is presented of 80 patients with ischemic heart disease (IHD): 37 patients with a low reaction of the cardiac rhythm to physical load--chronotropic insufficiency (CHI) and 43 patients with an adequate reaction of the cardiac rhythm to loads. Physical working capacity was evaluated by the strength of threshold load, pulsepressure double product, rest quotient, oxygen pulse, oxygen consumption per 1 kgm of work. Interval between the 1 and 2 examination--6.5 years. It was shown that CHI in IHD does not influence the prognosis of the disease and does not reflect the grade of its severity. They are, however, the marker of involvement of the atria. Chronic insufficiency in ischemic heart disease makes it difficult to objectively evaluate the physical working capacity. PMID- 1891845 TI - [Effect of the depth of myocardial infarction on the tolerance to physical exertion and hemodynamics in patients in the early rehabilitation period]. AB - Veloergometry (VEM) with determination of the threshold load power and indices of the hemodynamics in 135 patients with a varying depth of myocardial infarction (MI) with an uncomplicated course showed that the presence of asymptomatic coronary insufficiency limiting the tolerance to physical load does not allow to evaluate the physical state depending on the MI depth. Hemodynamic provision in loads and rest is determined by the functional state of the myocardium and does not always depend on the MI depth. VEM and determination of hemodynamic indices is of importance for revealing difference in the physical working capacity of patients with different MI depth, asymptomatic coronary insufficiency in patients with uncomplicated MI. PMID- 1891846 TI - [Incidence of cardiovascular diseases in the workers of deep coal mines]. AB - Examined were 1345 miners working in deep coal mines (temperature 27 degrees C and higher) and non-deep mines (temperature not exceeding 26 degrees C). It was found that increased temperature against the background of other noxious factors of the mine environment and strenuous physical work further the development of diseases of the cardio-vascular system (hypertensive disease, vegetovascular dystonia, ischemic heart disease). PMID- 1891847 TI - [Relation between calcium intake with food and arterial pressure in metallurgists of Donbass]. AB - Food rations and 24-hour urinary excretion of calcium were evaluated in 1100 metallurgists and revealed a distinct relationship between low consumption of calcium with food due to reduced intake of milk products and the incidence of elevated arterial pressure levels. This relationship did not depend on age and professional factors. PMID- 1891848 TI - [Clinico-functional evaluation of chronic obstructive lung diseases in association with hypertension]. AB - A study of 108 patients with chronic obstructive lung diseases revealed in 36 of them concomitant hypertensive disease. This association is accompanied by a benign course of each of these diseases. A study of the central hemodynamics showed the presence of hemodynamic changes typical of hypertensive disease. PMID- 1891849 TI - [Effectiveness of long-term treatment with vasodilators in patients with artificial pacemakers]. AB - The effect of long-term use of venular and arterial vasodilators (molsidomin and nifedipin) on the clinical course and hemodynamic indices was studied in 52 patients with artificial pacemakers. The choice of vasodilator was based on an acute drug test. In the presence of hypertensive disease the calcium antagonist nifedipin was used, in cases of dilatation of the cardiac compartments molsidomin was used. Combination of both drugs was used in patients in whom the acute drug test did not allow to prefer any of the drugs. It is concluded that three-month's treatment resulted in positive changes of the hemodynamics, reduction of the severity of cardiac insufficiency. Side-effects were practically absent. PMID- 1891850 TI - [Bile acid levels in the serum and the state of liver blood flow in patients with rheumatic mitral heart disease]. AB - The total and fractional content of blood bile acids (BA) was studied by the method of thin-layer chromatography and rheohepatography was performed in 87 patients with rheumatic mitral disease (mitral stenosis and associated mitral heart disease with prevalence of stenosis). There was a direct dependence between the degree of clinical and rheohepatographic signs of disorders of the hemodynamics and increase of the level of serum BA, a more pronounced therapeutic effect with normalization of BA, concentration in the blood after complex treatment using hepatotropic drugs than with use of traditional drugs (non steroid antiinflammatory, cardiac glycosides, diuretics and others.). PMID- 1891851 TI - [Dynamics of body fat mass and blood circulation in young men with obesity]. AB - The body fat mass (BFM), central and peripheral hemodynamics was studied in 112 adipose males (age: 18-32 years) after a 18-24 days hospital treatment and 3-3.5 years later. It was found that an increase of the BFM was accompanied by a distinct increase of the AP level, a tendency to reduction of the cardiac ejection, volume rate of the arterial blood flow, increase of the peripheral vascular resistance, venous capacitance, venous tone. The dynamics of circulation indices in reduction of the BFM reflect normalization of the cardiac and vascular function. Obtained data evidence diverse changes of the hemodynamic indices in progression, regress and stable course of adiposity in young males. PMID- 1891852 TI - [Immunologic disorders in patients with primary hypothyroidism]. AB - Most patients with primary hypothyroidism showed changes in the immune status manifested in a reduction of the number and functional activity of T-lymphocytes, increased sensibilization of lymphoid cells to thyreoglobulin, content of B lymphocytes, serum immunoglobulins of M, G classes, antithyreoglobin antibody titer and circulating immune complexes. The frequency and grade of immune disorders are directly related to the severity of the disease. The most pronounced changes were revealed in spontaneous hypothyroidism. PMID- 1891853 TI - [The role of androgen-estrogen relations in the morphologic differentiation of male organism during genital development retardation and primary hypogonadism]. PMID- 1891854 TI - [Fibrinolytic activity of the urine in patients with diabetic glomerulosclerosis]. AB - The summary fibrinolytic activity of the urine (SFAU) was studied in 39 patients with diabetic glomerulosclerosis (DGS), 12 patients with diabetes mellitus (DM) without renal involvement, 8 patients with reduced glucose tolerance and 20 healthy subjects. The level of plasmin, plasminogen activators, plasminogen activation inhibitors and antiplasmins in the concentrated urine were also determined. Diabetic patients without clinical manifestations of DGS revealed a significant reduction of SFAU, plasmin activity and plasminogen activators. A significant reduction of the fibrinolytic activity of the urine was found in DGS without chronic renal failure and especially in DGS with chronic renal failure. It is concluded that reduced levels of urinary plasminogen activators may be used as an index of preclinical stages of renal involvement. PMID- 1891855 TI - [Glucagon and prostaglandins in stomach and duodenal diseases]. PMID- 1891856 TI - [Blood gastrin and ultrastructure of gastrin-producing cells in chronic gastritis with secretory insufficiency]. AB - The content of basal gastrin and ultrastructure of gastrinproducing cells was studied in 81 patients showing chronic gastritis with secretory insufficiency. The highest level of gastrin was revealed in the blood of patients with diffuse atrophic gastritis, moderately increased--focal atrophic gastritis. The blood gastrin was reduced in patients with antral gastritis. A study of the ultrastructure of gastrinproducing cells revealed their high functional activity in diffuse atrophic gastritis and a moderate in focal atrophic gastritis. Changes of the gastrin level and ultrastructure of gastrinproducing cells should be considered in the choice of treatment methods. PMID- 1891857 TI - [Endolymphatic polychemotherapy with local UHF hyperthermia in the surgical treatment of rectal neoplasms]. AB - To reduce the risk of intraoperative metastases and increasing ablastic principles in radical surgical treatment of patients with cancer of the rectum the authors developed a scheme of preoperative treatment including endolymphatic polychemotherapy and UHF-hyperthermia. 5-fluorouracil and platidiam were used in the treatment of 30 patients with different histological types of adenocarcinomas of the rectum (grade III-IV). After treatment the viable epithelial component in the tumour was 26.5% as compared with 44.8% in the control. The effect of treatment was favourable both objectively and subjectively. The treatment was well tolerated. PMID- 1891858 TI - [Intravenous digital subtraction angiography in the diagnosis of urological diseases]. AB - The diagnostic possibilities of intravenous digital subtraction angiography (DSA) were evaluated in 2393 patients. The diagnostic value was 97.2%. DSA is contraindicated via the subclavian vein in children, inadequate preparation of the patients, vein abnormalities. The informative value was 92% in vasorenal hypertension, 100% in renal abnormalities, 85% in renal tumours. Intravenous DSA may be a screening method in the diagnosis of hypertension of unclear etiology, abnormalities of the upper urinary tract, while in tumours, especially of small size, DSA is a supplementary method to ultrasound and CT. The method is of economic importance. PMID- 1891859 TI - [Psychopathological characteristics of autonomic dysfunction syndrome in patients exposed to small doses of ionizing radiation]. PMID- 1891860 TI - [Large granule-containing lymphocytes in patients with infectious mononucleosis]. AB - A study of 50 children with infectious mononucleosis is presented. Results indicate that the content of large granule-containing lymphocytes corresponds to the severity of the clinical course of infectious mononucleosis. Absence of large granule-containing lymphocytes evidences severe course of the disease while their appearance favoured normal reconvalescence of patients. A high content of large granule-containing lymphocytes is an evidence of a favourable prognosis of the course of infectious mononucleosis. PMID- 1891861 TI - [Clinico-hematologic characteristics of preleukemia]. PMID- 1891862 TI - [Biochemiluminescence in the early differential diagnosis of infectious inflammatory diseases and acute leukemia]. AB - Spontaneous and induced biochemiluminescence (BCL) of blood plasma and hemolysate of erythrocytes was studied in 563 patients with infectious-inflammatory diseases with leukemoid reactions of lymphatic and myeloid type. It was established that infectious-inflammatory diseases are characterized by an increase of induced BCL of blood plasma and erythrocyte hemolysate. Revealed were 11 persons with low values of spontaneous and induced BCL; 10 of them showed later clinico hematological symptoms of acute leucosis. It is concluded that the use of BCL for differential diagnosis of leucemoid reactions in infectious-inflammatory diseases and acute leucoses is of importance. PMID- 1891863 TI - [Spectrography as a method in the pathologic anatomy]. PMID- 1891864 TI - [Esophagogastroduodenoscopic indices in patients with calculous cholecystitis]. AB - It is concluded on the basis of probability analysis about the necessity of including esophagogastroduodenoscopy in the complex of preoperative examination of patients with calculous cholecystitis. Data of 1050 consecutive esophagogastroduodenoscopies for calculous cholecystitis confirm from clinical positions the expediency of the mathematically based tactics. PMID- 1891865 TI - [Neurologic disorders in AIDS (using the data from Republic Burundi)]. AB - The authors analyze 184 cases of AIDS in women treated from 1988 through 1990; 44.5% were 26-35 years old. The main diagnostic criteria of AIDS are described. The main neurological manifestations of a AIDS and their characterization in different concomitant infection. Treatment resulted in an improvement in 77% of cases. Fatal outcomes were in 29 patients (15.8%). The main causes of death were meningitides and pneumopathias of different etiology. PMID- 1891866 TI - [Protracted course of acute pneumonias and their prophylaxis]. AB - Different specific (immunological) and non-specific factors predisposing to protracted course of acute pneumonia were evaluated acute pneumonia and diagnostic errors. The course of pneumonia was protracted in 126 (48.9%) patients. Measures for prophylaxis of protracted course of pneumonia are described including increase of defensive forces of the body, biophysical and biochemical mechanisms of protection of the bronchopulmonary apparatus, removal of causes furthering slow resolution of the inflammatory process in the lungs. PMID- 1891867 TI - [Adverse effect of etiotropic agents in patients with tuberculosis]. AB - Side-effects of antitubercular drugs were evaluated in 662 patients with tuberculosis. Simultaneously 406 of them suffered of chronic alcoholism, 94 suffered of heavy drinking and 162 were not alcohol abusers. The frequency of side-effects in patients with tuberculosis was 31.5% and 56.4% in those with concomitant alcoholism. The latter showed more frequently negative responses to streptomycin. The latter showed more frequently negative responses to streptomycin, ethionamide, rifampycin and kanamycin. They developed toxic reactions that were three times more frequent than in those without alcohol abuse and were accompanied by exacerbation of diseases of the liver, stomach, heart, CNS, peripheral nervous system. PMID- 1891868 TI - [Tactics and emergency aid in acute chemical poisoning]. AB - Successful treatment of acute intoxications should include early urgent measures, use of specific antidotes, polysymptomatic and polysyndromic treatment. It is an error to delay intensive care until laboratory identification of the toxicant. Only combined use of methods directed to potentiate natural urocesses, intra--and extracorporal detoxication allows to improve treatment results of treating acute intoxications. PMID- 1891869 TI - [Changes in the phase structure of the left ventricle systole in patients with obliterative atherosclerosis of the lower extremities after treatment with naphthalane baths]. AB - Fifty six patients with IHD and stenocardia, hypertensive disease were treated at the Naphthalan health resort. It was found that napthalane baths in the sitting position stimulate adaptation reserves of the body, improve the cardiac function, systemic and regional hemodynamics and may be used in the complex treatment of patients with obliterative atherosclerosis of the lower extremities including association of this disease with IHD and hypertension. PMID- 1891870 TI - [Lithonite vacuum phonophoresis in the combined treatment of patients with rheumatoid arthritis]. AB - A compound of lithium and nicotinic acid--lithonite was used phonophoretically in complex with non-steroid antiinflammatory drugs in 40 patients with rheumatoid arthritis according to a method developed by the authors. The efficacy of complex treatment was 95%. There were no side-effects. Further perfection of this method is desirable. PMID- 1891871 TI - [Diet, containing natural fruit and berries paste in the secondary prophylaxis of ischemic heart disease]. PMID- 1891872 TI - [Immunoenzyme analysis for the detection of HIV antigens (its use, potentials and limits)]. PMID- 1891873 TI - [The anomalous isoelectric properties of influenza virus matrix protein M1]. AB - The isoelectric point (pI) values of matrix protein M1 of influenza A, B, and C viruses, calculated theoretically on the basis of its primary structure, were found to be about 10.0. However, experimental pI determination by electrofocusing in ampholyte-containing polyacrylamide gel showed it to be 5.0 for M1 protein isolated from A/WSN/33 (H1N1) and A/Aichi/2/68 (H3N2) viruses by mild deproteinization with nonionic detergents. This marked discrepancy between experimental and theoretical pI values indicated that influenza virus matrix protein M1 possessed an unusual tertiary structure and/or intensive posttranslational addition of charged residues. PMID- 1891874 TI - [The role of antibody functional activity in the protection of people against influenza]. AB - Indices of the functional activity of specific serum antibodies (IFAA) before and after outbreaks of influenza A (H3N2) and B were determined in 164 subjects of 18 20 years of age from the military communities observed in 1987-1988. The IFAA were calculated on the basis of kinetic HI tests followed by computer processing according to the program developed by the authors. The IFAA were found to indicate the protection of human subjects against influenza, reflecting the state of resistance to influenza more exactly than antibody titres. High initial IFAA correlated with lower severity of influenza infection. The IFAA to the same strain may differ significantly in individual subjects. In patients with influenza the time course of antibody titres did not coincide with dynamic changes in IFAA. PMID- 1891875 TI - [The protective effect of hemagglutinin-specific monoclonal antibodies in experimental influenza infection]. AB - Experiments in mice showed a high protective effect of monoclonal antibodies (MCA) to influenza A/Krasnodar/101/59 (H2N2) virus hemagglutinin, possessing neutralizing activity in ovo. A 100% protective effect was observed upon intranasal administration of MCA Kp/101-3 48 hours before infection, and 90% effect upon administration of MCA 96 hours before infection. A 100% therapeutic effect was observed upon intranasal administration of MCA Kp/101-3 less than 24 hours postinfection and 70% therapeutic effect was achieved by administration of these MCA 48-72 hours postinfection. PMID- 1891876 TI - [Experimental hepatitis E infection in piglets]. AB - A sample of patient's faeces containing virus-like particles (VLP) of 27-34 nm was obtained during an outbreak of hepatitis E in the Kirghiz SSR. The identity of the VLP to hepatitis E virus and etiological association with the disease were demonstrated by immune electron microscopy and infection of Macaca fascicularis monkeys. This isolate of hepatitis E virus is able to induce experimental infection in domestic piglets which was very similar to experimental hepatitis E in primates when infected orally, intravenously and by the combined routes. The clinical manifestations included acute biochemical and histological hepatitis, excretion of hepatitis E virus in faeces, icteric sclerae and skin, hepatitis virus presence in the material from mesenteric lymph nodes. Immunosuppression aggravated hepatitis E infection in piglets. Piglet-to-piglet transmission of hepatitis E virus was demonstrated. During passages of the virus in piglets a shortening of the incubation period and the absence of jaundice was observed. PMID- 1891877 TI - [The protective activity of the attenuated strain 15 of the Venezuelan equine encephalomyelitis virus in rodent infection via the respiratory tract]. AB - Administration to rodents (Syrian hamsters, mice, guinea pigs, rabbits) of minimal doses of attenuated strain 15 VEE (up to 20 ImD50) provided protection against respiratory challenge with a highly virulent strain of Venezuelan equine encephalomyelitis virus. The protection is observed in a wide range of doses (up to LD50 hundreds and even thousands). PMID- 1891878 TI - [The Mopeia virus induces pH-dependent "fusion from within" in a BHK-21 cell culture]. AB - The capacity of BHK-21 cell culture to produce Mopeia virus (Arenaviridae family) to form syncytium upon acidification of the culture medium to pH 5.5 and lower was demonstrated. The cell fusion requires their active virus production: a virus titre in the culture medium must be at least 10(5) PEU/ml. The inhibition of virus multiplication with ammonium chloride as well as treatment of the cells before the medium acidification with immune serum reduced syncytium formation markedly. No cell fusion was observed upon acidification of the medium immediately after virus adsorption to cells. Thus, the observed cell fusion under the influence of the virus is an "internal fusion" and confirms our previous data on the endocytosis mode of arenavirus penetration into the cell. PMID- 1891879 TI - [Cloned variants of the L-IVP strain of the vaccinia virus]. AB - Genomes of vaccinia strain L-IVP and its cloned variants were investigated by restriction and Southern blotting analysis. The strain L-IVP was shown to be heterogeneous and to consist of variants which differed in the genome structure and properties. Clone 1 derived from L-IVP was less reactogenic than the original strain for rabbits inoculated intradermally and had mutations in the right terminus of the genome. All the clones were stable in passages in the chorioallantoic membranes of developing chick embryos and roller BHK-21 cell cultures. PMID- 1891880 TI - [The sensitizing properties of the ballast admixtures in human leukocyte interferon]. AB - Due to the features of its production technology, human leukocyte interferon (HLI) for intranasal administration is likely to contain ovalbumin (OA). Commercial batches of HLI were tested for the presence of OA responsible for the sensitizing effect of HLI given intranasally. The content of OA in commercial batches of HLI was shown to vary widely and to exceed by far the concentrations having the sensitizing effect. As a result of these studies, the upper limit of OA content was established and the technology of HLI production was modified. These measures permitted production of commercial batches of HLI with OA content not exceeding 0.05 micrograms/ml. PMID- 1891881 TI - [The immunoblot as a method for detecting positive specimens in isolating the human immunodeficiency virus and demonstrating cells sensitive to the virus]. PMID- 1891882 TI - [A cell line with decreased interferon susceptibility as a model for studying cellular resistance to the preparation]. PMID- 1891883 TI - [An experimental evaluation of the attenuated strain 15 of the Venezuelan equine encephalomyelitis virus]. PMID- 1891884 TI - [The use of enforcing solutions of different composition in performing lanthanide immunofluorescent analysis]. PMID- 1891885 TI - [The diagnostic potentials of the nucleic acid molecular hybridization method for demonstrating the tick-borne encephalitis virus]. PMID- 1891886 TI - [The antiviral properties of lincomycin]. PMID- 1891887 TI - [The decontamination of cell cultures of Mycoplasma by using the antibiotic olivomycin]. PMID- 1891889 TI - [A brief report on the performance of AIDS research in the State Scientific and Technical Program "The control of the most prevalent diseases" in 1990]. PMID- 1891888 TI - [Nontraditional approaches to the development of antiviral chemotherapeutic preparations]. PMID- 1891890 TI - [The potentials of echotomography in the diagnosis of diseases of the liver, biliary tract and pancreas in the presence of the extrahepatic cholestasis syndrome]. AB - 2260 patients with gastroenterologic diseases were examined by ultrasound tomography (sector echotomograph). In 47 (2.8%) of the patients echographic signs of extrahepatic cholestasis were found: dilated ductus choledochus (65.9%), dilated ductus hepaticus (34%), dilated intrahepatic biliary ducts (34%), echographic data for stones in the biliary ducts (54.5%), dilated ductus pancreaticus (18.1%), focal changes in pancreas and liver (13.6%), hydrops of the gall bladder (6.8%). The patients were classified in two groups: in the first group the ultrasound tomography succeeded in proving the cause of the cholestasis (75%) while in the second group the cause of the cholestasis remained unproved (25%), which required other additional examination such as endoscopic retrograde cholangiopancreatography (ERCP) and computed tomography. In two patients the cause of cholestasis was determined intra operationem. The site of the obstruction was determined by the ultrasound examination in all patients. The importance of the ultrasound examination of the biliary ducts and its advantages as a nonaggressive screening method for diagnosis of diseases with obstructive jaundice is pointed out. PMID- 1891891 TI - [Epithelioid leiomyoma of the stomach--its current diagnosis]. AB - A case of a 62-years-old woman with mobile tumor in the upper abdomen is reported. With the contemporary methods of examination, including percutaneous thin needle biopsy, the diagnosis of epithelioid leiomyoma of the stomach was established. The patient was successfully treated surgically. The frequency of these benign gastric tumors, their clinical course, diagnosis and treatment are discussed. PMID- 1891892 TI - [2 cases of primary hyperaldosteronism]. AB - Two clinical cases of women with primary hyperaldosteronism are reported. The patients presented with arterial hypertension, muscular weakness and paresthesia. Severe hypokalemia was found which was resistant to intravenous infusions of potassium but was successfully treated with low daily doses (100-200 mg) of spironolacton, an aldacton antagonist, in the course of 3-4 days. In one of the patients the primary hyperaldosteronism was related to aldosterone secretion by the cells of a malignant corticosteroma, proved histologically. A successful operation led to full recovery of the patient. In the other patient there was an idiopathic form of primary hyper aldosteronism caused by bilateral hyperplasia of the suprarenal cortex. Contemporary diagnostic and therapeutic possibilities in primary hyperaldosteronism as well as the importance of the examination of potassium serum level and kaliuria in the patients with arterial hypertension for the timely and successful diagnosis and treatment of primary hyperaldosteronism are pointed out. PMID- 1891893 TI - [The 25th anniversary of the Department of Allergology--let us look back at the past]. PMID- 1891894 TI - [Jaundice--the current successes in its diagnosis and treatment]. PMID- 1891895 TI - [Prostaglandins, liver cirrhosis and kidney function]. PMID- 1891896 TI - [The drug treatment of cardiogenic shock--our experience]. AB - For the period 1970-1989 in the intensive care unit of the National Center for Cardiovascular Diseases, 178 patients with cardiogenic shock were treated and died. These patients were studied retrospectively. In all patients an acute myocardial infarction was proved clinically and post mortem. The patients were classified into two groups--group A--those treated during the period 1970-1975 and group B--those treated during the period 1985-1989. The analysis of the risk factors and the time of hospitalization since the onset of the clinical symptoms showed no differences between the two groups. In the therapeutic programme of group B new contemporary means and methods, such as dopamine, vasodilators and electrostimulation, were included. This accounts for the longer survival of the patients from this group (about 60% of the patients survived more than 24 h), which allows them a chance to overcome this fatal condition. PMID- 1891897 TI - [The characteristics of those who have died with primary or recurrent myocardial infarct]. AB - In 93 decreased patients, 31 with first myocardial infarction and 62 with repeated myocardial infarction, the following indices were studied: risk factors, previous history, clinical onset, complications, ECG localization, time and cause of death, pathologicoanatomical changes. There was a tendency toward a greater frequency of cardiogenic shock in the patients who died during their first infarction. In the patients who died during a repeated infarction the following events were significantly more frequent: pulmonary thromboembolism (9.6%), dilatation (8.1%), recurrence (8.1%) (p less than 0.01); chronic cardiac failure (25.8%), episodes of clinical death (25.8%) (p less than 0.001); conduction rhythm disturbances (75.8%) (p less than 0.05). Transmural infarction was found in 96.7% of the patients of the first infarction group vs 82.2% of the patients of the repeated infarction group (p less than 0.05). A statistically significant difference for the time of death was found only for the group patients who died after the 7th day of the infarction--0% for the first infarction group and 25.8% for the repeated infarction group (p less than 0.001). Cardiogenic shock was a significantly more frequent cause of death for the patients of the first infarction group (87.1%) than for the patients of the repeated infarction group. PMID- 1891898 TI - [Mesangial C3-glomerulonephritis]. AB - 12 patients with mesangial C3-glomerulonephritis, 7 women and 5 men, aged 16-42, mean age 29.7 years, were followed up for 1-18 years, mean time 5.7 years. The disease was manifested most often by macroscopic hematuria or low degree proteinuria. Single patients had arterial hypertension. In only one patient there was a nephrotic syndrome. For the period of observation, impairment of the renal function was found in none of the patients. PMID- 1891899 TI - [Changes in the lungs in progressive systemic scleroderma]. AB - In 24 patients with progressive systemic scleroderma the respiratory disturbances, X-ray, scintigraphic and clinical deviations as well as the statistical correlations between them are described. The functional examination of respiration revealed lowered diffusion capacity, restrictive type of ventilatory failure and hypoxemia as the most frequent disturbances. The functional examination of respiration is correlated with the X-ray changes in the lungs in these patients. PMID- 1891900 TI - [Gemfibrozil in the treatment of hyperlipoproteinemias]. AB - 30 patients with primary hyperlipoproteinemia (type II and IV according to Fredrickson) were treated with Gemfibrosil (Gevinon--film tablets of 450 mg of "Parke-Davis Company") for a period of 45 days with a daily dose of two tablets taken with the evening meal. The results of the treatment were a decrease of the total cholesterol (with 16.34%), of triglycerides (with 34.50%), of low density lipoproteins (with 10.76%) and of very low density lipoproteins (with 49.21%) and an increase of the high density lipoproteins (with 2.34%). Gevilon was well tolerated. No side effects requiring discontinuing of the treatment were registered. PMID- 1891902 TI - [A new classification of gastritis--Sydney, 1990]. PMID- 1891901 TI - [An evaluation of Visidex test strips in the blood sugar control of diabetics]. AB - The test stripes Visidex for visual evaluation of glycemia were tested clinically. The results were compared with a reference laboratory method for blood sugar measurement. A correlation coefficient of r = 0.971 with 74% coincidence in the same glycemic interval was found. The test stripes are suitable for blood sugar self-control in domestic conditions. PMID- 1891903 TI - [Stomach and duodenal lesions in patients with acute organophosphorus pesticide poisonings]. AB - Gastric and duodenal mucosa changes were studied by means of fibrogastroduodenoscopy and targeted biopsy in 35 patients, 23 men and 12 women, aged 18 to 68 years, with acute poisoning with phosphororganic pesticides. In 33 of the patients the poisoning occurred through oral and in 2 patients through cutaneous route. 13 patients were with a light, 14--with a moderate and 8--with a severe form of poisoning. In 31 patients (88.57%) edema and hyperemia were found, in 15 patients single and in 8 p. multiple erosions and in 4 p. ulcers were found, but in the duodenum they were more rare. The microscopic examination of the biopsies revealed variable changes--from edema, through focal accumulation of siderophages and single inflammatory infiltrates up to a severe fibrino suppurative-necrotic process. A direct correlation between the severity of the lesions and the severity of the poisoning was found. PMID- 1891904 TI - [Pneumocardiodilatation in patients with esophageal achalasia]. AB - Patients with esophageal achalasia, treated by pneumocardiodilatation with "Esophageal balloon dilatation" of the firm "Cook"--Denmark with a size of 22 mm in an inflamed state, were followed up for a period of 8 years. The result of the first course of pneumocardiodilatation treatment was unsatisfactory in 13.9% of the patients and they were recommended a surgical treatment. In the remaining patients the duration of the treatment effect lasted from 10 months up to 8 years. In 16.1% of the patients repeated redilatations were needed at intervals of 10 to 22 months. For this group of patients a decision should be made how to proceed further--with repeated pneumocardiodilatations or with surgical treatment. PMID- 1891905 TI - [Manometry of the upper gastrointestinal tract in esophageal reflux disease]. AB - Infusion manometry of the esophagus and the stomach after the permanent dynamic method of Winans [correction of Wynas] and Harris was carried out on 52 patients (30 women and 22 men) with hiatal hernia, volvulus of the stomach or peptic ulcer disease. Altogether 75 examinations were performed--35 preoperative and 40- postoperative. The mean preoperative pressure of the inferior esophageal sphincter was 9.1 (from 0 to 15) mmHg and the mean postoperative pressure was 18 (from 12 to 211 mmHg). The mean preoperative length of the inferior esophageal sphincter was 1.4 (from 0 to 4) cm and the mean postoperative length was 2.5 (from 1 to 6) cm. In 12 patients motor disturbances of the tubular esophagus were found: symmetric, hyperpersistaltic waves (Richter's nutcracker symptom)--in 3 patients, hypomotility--in 5 patients, diffuse esophageal spasm--in 4 patients. Esophageal manometry is a valuable noninvasive method for the functional diagnostic of the reflux disease and the motor esophageal disturbances as well as for the assessment of the postoperative function of the inferior esophageal sphincter. PMID- 1891907 TI - [Endoscopic assessment of hemorrhage from the gastrointestinal tract]. AB - The causes of gastrointestinal bleedings was assessed by fiber gastroscopy, rectoromanoscopy and fiber colonoscopy. The most frequent causes of bleedings from the upper gastrointestinal tract are gastric and duodenal ulcers, erosive hemorrhagic gastritis, gastric cancer, liver cirrhosis with bleeding from varicose veins, polyps, diverticuli, Mallory-Weiss syndrome, etc. The most frequent causes of bleedings from the lower gastrointestinal tract are hemorrhoids, anal fissures, colonic polyps, chronic ulcerohemorrhagic colitis, rectal carcinoma, etc. The diagnostic importance of urgent endoscopic examinations is pointed out. PMID- 1891906 TI - [Campylobacter (Helicobacter) pylori in chronic erosive gastritis, duodenitis and gastroduodenitis]. AB - The presence and degree of manifestation of Campylobacter (Helicobacter) pylori in gastroduodenal mucosa were studied in 100 patients (56 men, mean age 51.4 years, and 44 women, mean age 46.5 years) with endoscopically proved chronic erosive gastritis (52 patients), erosive duodenitis (36 patients) and erosive gastroduodenitis (12 patients). The examinations revealed the presence of Campylobacter (Helicobacter) pylori in mean 77% of the patients with erosive gastritis, duodenitis and gastroduodenitis. Campylobacter (Helicobacter) pylori was found most often in patients with chronic erosive duodenitis--83.3%, whereas in the patients with erosive gastritis it was found in 73.07%. In 83.33% of the patients with chronic erosive gastritis, duodenitis and gastroduodenitis the campylobacter infection was well manifested--(++) according to Le Bodie et al (1987). The results allow the conclusion that one of the important pathogenetic factors of erosive gastritis, duodenitis and gastroduodenitis is the Campylobacter (Helicobacter) pylori infection of gastroduodenal mucosa. PMID- 1891908 TI - [Hyperbaric oxygenation as a part of the treatment of chronic ulcerohemorrhagic colitis]. AB - 34 patients with chronic ulcerohemorrhagic colitis in exacerbation were treated with hyperbaric oxygenation in addition to the routine therapy. Two chambers model "Drager" 1000 and 1200 were used. The total course of treatment included 10 12 seances with 60-75 min. exposition each. All patients improved significantly after the first 5-6 seances. The results of the treatment back up the use of hyperbaric oxygenation in the treatment of chronic ulcerohemorrhagic colitis. PMID- 1891909 TI - [The cellular-humoral immune factors of patients with cholelithiasis uncomplicated and complicated by an inflammatory process]. AB - 82 patients-10 p. with uncomplicated cholelithiasis, 8 p. with chronic calculous cholecystitis, 34 p. with choledocholithiasis with stenosing papillo-odditis--and 30 healthy controls were examined, with monoclonal antibodies of the firm "Becton Dickinson". The following immunocompetent cellular clones and subclones were examined: CD3+, CD16+, CD4+, CD8+, CD19+ CD4/CD8, HLA-DR+, CD3+. The results were read with analyzer for fluorescently marked activated cell clones "FACS-TAR". The serum IgA, IgM, IgG, C3-C4 complement fractions and circulating immune complexes were also examined. The analysis of the results shows that in the complicated cases of cholelithiasis with an inflammatory process in the biliary ducts several humoral and cellular immune factors take part. PMID- 1891911 TI - [The "sump" syndrome in cholecystectomy patients--its clinical characteristics and endoscopic treatment]. AB - "Sump" syndrome is a rare complication of choledochoduodenoanastomosis (ChDA). 15 patients are discussed, 13 women and 2 men, mean age 47.7 years (32 to 67 years). The clinical picture is classified into two groups: I. with symptoms mainly from pancreas involvement (recurrent pancreatitis and other lesions of the pancreas) and functioning ChDA--10 patients; 2. with symptoms arising from simultaneous impairment of the biliary ducts and pancreas and a tendency toward obliteration of ChDA--5 patients. All patients had been cholecystectomized at various times in the past. To all 15 patients endoscopic papillosphincterotomy was performed which led to restoration of pancreatic drainage in the patients with functioning ChDA and of bile drainage in the patients with obliterated ChDA. The conclusion is that papillosphincterotomy is a reliable, cheap and less risky method than surgical intervention for treatment of "sump" syndrome in patients without suprapapillary stenosis of the biliary duct. PMID- 1891910 TI - [The extracorporeal lithotripsy of gallstones in Bulgaria]. AB - Extracorporal lithotripsy is a new, modern method of treatment of gallstone disease. The effect of the treatment was evaluated as follows: full--fragments up to 2 mm in size (in 60.5% of the patients), partial--fragments between 2 and 5 mm in size (in 30.1% of the patients) and no effect--fragments larger than 5 mm or lack of fragmentation (in 9.4% of the patients). Complications during the manipulation and after it were very rare--allergic in 1.7% and obstructive in 6.7% of the patients. In only 3 patients on operation had to be done. 84 patients were followed up for 270 or more days. In 10.4% of the patients a full clearance of the fragments was found, and in 28.2% of the patients there was only a reduction of their number. Extracorporal lithotripsy followed by litholytic therapy is a perspective method for gallstone disease treatment. It has wide indications, few contraindications, is well tolerated and is with a low complication rate. PMID- 1891912 TI - [The so-called postcholecystectomy syndrome in light of the results of endoscopic retrograde cholangiopancreatography]. AB - The term "postcholecystectomy syndrome" indicates etiologically and pathogenetically various lesions of the organism related to variably expressed symptoms of pain and dyspepsia. The author has performed endoscopic retrograde cholangiopancreatography (ERCP) to 60 patients with "postcholecystectomy syndrome" to find out what underlies this syndrome. In 34 (56%) of the patients the biliary ducts were dilated. The most frequent cause of this was Vater's papilla stenosis, which was found in 26 patients (43%). The author is of the opinion that this stenosis preceded the cholecystectomy and was the result of inflammatory processes related to cholelithiasis. In 20 patients stones were found in the biliary ducts, single or multiple. In most cases the stones in the biliary duct had been missed during the cholecystectomy. In some patients the stones in the biliary duct were formed after the operation. In 26.6% of the patients ERCP helped in discovering other diseases such as chronic pancreatitis, duodenal ulcer and peripapillary diverticulum which are in the basis of the "postcholecystectomy syndrome". The author recommends to every patients with persistent complaints after cholecystectomy ERCP to be performed in order to find out the cause of the complaints and determine the correct treatment- medicamentous or surgical. PMID- 1891913 TI - [The differentiation of cirrhotic from malignant ascites by ultrasonic tomography of the gallbladder]. AB - 99 patients with ascites (60 patients with liver cirrhosis and 39 patients with peritoneal carcinosis) were examined by ultrasound tomography of the gall bladder. In most of the cirrhotic patients a thick gall bladder wall was found (7.7 +/- 3.4 mm) often with a three-layer structure. The gall bladder wall of the patients with peritoneal carcinosis was most often not thickened (2.5 +/- 1.6 mm). The difference is statistically significant (p less than 0.1). Thickening of the gall bladder wall was found in both groups of patients by a decreased serum albumin level. The ultrasound tomography of the gall bladder could help in the differentiation of cirrhotic from malignant ascites, especially in combination with determination of the serum albumin level. PMID- 1891915 TI - [Brief definitions of medical ethical concepts. 10. Gene technology. IV. Germ cell therapy]. PMID- 1891914 TI - [The diagnostic value of echography in hepatic echinococcosis]. AB - The ultrasound method of examination led to revolutionary changes in the diagnosis of liver echinococcosis [correction of Echinococcus]. The ultrasound image of this disease, which is common in the region, is presented. The ultrasound method is compared with other diagnostic methods and its importance is pointed out. The ultrasound method of examination is a reliable means for the diagnosis of liver echinococcosis [correction of Echinococcus]. PMID- 1891916 TI - [Significance of prophylactic ovariectomy at the time of uterus extirpation for prevention of an ovarian carcinoma]. AB - There is no general recommendation with regard to a certain age, after which prophylactic oophorectomy should be performed at the time of hysterectomy. We investigated how many patients who were treated for ovarian cancer at the University Clinic of Obstetrics and Gynecology in Graz between 1980 and 1989, had a history of hysterectomy because of benign uterine disease. In 42 of 382 patients with ovarian cancer (11%), a hysterectomy had been performed 2 to 43 years before the diagnosis of ovarian cancer. 12 of the 42 patients with ovarian cancer and previous hysterectomy (29%) additionally had unilateral oophorectomy because of benign tumors of the ovary. In 79% of patients, hysterectomy was carried out before the 45th year of age and in 86% of patients before the 50th year of age. Thus, prophylactic extirpation of sound ovaries before the age of 50 years does not seem to be generally indicated in patients with retained ovarian function who undergo hysterectomy. However, the rare genetically determined ovarian cancer is the exception to the rule. PMID- 1891917 TI - [Seizures in old age]. AB - The important differential diagnosis between epileptogenic versus non epileptogenic attacks becomes increasingly difficult with elderly patients: 1) Vasovagal syncopes may occur abruptly, not infrequently with injuries caused by the sudden fall ("Blitz-Synkope"). Other generalized non-epileptic seizures include drop-attacks, amnesic episodes, prolonged syncopes, and seizures caused by faulty metabolism. 2) Focal non-epileptic seizures in advanced age are mainly TIA and prolonged TIA (PRIND). Complicated migraine is more typical for the younger age group. In this connection it must be kept in mind that 10% of TIA are caused by brain tumor, 20% can be traced to cardiac origin. 3) In connection with the non-epileptic seizures mentioned above there may appear singular irregular cloni without any rhythmical sequence. We have come to call this type of attacks "incidental convulsions". Especially in these cases differential diagnosis is of great importance with respect to basically different therapeutic measures. 4) First manifestations of epilepsy in advanced age are--regarding etiology--in the first rank symptoms of cerebral vascular disease or of intracranial tumors. 5) In the diagnostic approach it is necessary to keep in mind all the above-mentioned possibilities and to exploit every possible access to anamnestic exploration, with the patient as well as with his family, friends and colleagues. Essential auxiliary diagnostic methods include EEG, computed tomography, Doppler sonography, occasionally long-time EEG or ECG, in some cases NMR. PMID- 1891918 TI - [Questionnaire activities concerning atherosclerosis by lay people]. PMID- 1891919 TI - [The treatment of septicemia in childhood using time-spaced administration of antibiotic combinations]. AB - Theoretical consideration, empirical findings since 1972 and in vitro results had suggested that a combination of antibiotics for treatment of sepsis is more effective if the 2 or 3 antibiotics are not applied simultaneously but individually and sequentially at short intervals of 4 hours. Between January 1986 and March 1990 100 children were treated with spaced administration of antibiotic combinations at the University Hospital Innsbruck (Department of Paediatric). Causative agents isolated compared well to data published for other institutions; staphylococci were the dominating species. Anaerobic bacteria and fungi accounted for only 1% each, 60% of the cases were nosocomial infections. Overall, the fatality was 4%, a result significantly below the values reported in the literature for conventional therapeutic regimens. PMID- 1891920 TI - [Artificial insemination from a Catholic viewpoint]. AB - The Roman Catholic Church understands the human propagation as a common act of body and soul, which should not be destroyed either by contraception or artificial insemination. This thesis is based on the natural order and meaning of the unity of man and woman. Within its demands on the state, the church differentiates between artificial insemination of married persons and others. PMID- 1891921 TI - [Prenatal diagnosis and its consequences]. AB - The use of chorionic villi biopsy and amniocentesis as methods of the targeting and invasive prenatal diagnosis involves consecutive problems, which must be balanced with the medical legalization of both procedures. PMID- 1891923 TI - World progress in emergency surgery of the hand. PMID- 1891922 TI - [Ethical problems in extreme prematurity]. AB - I examine the question whether it is always morally obligatory to sustain the life of a premature infant and come to the conclusion that this is not the case. Touching on questions concerning the value of life, I argue that it is not always in a premature infant's best interests to have its life sustained. I sharply distinguish my patient-centered perspective from that of the Nazis. Finally, I raise the question of how a premature infant should be treated when the decision has been made to allow it to die. PMID- 1891924 TI - The emergence of hand surgery. PMID- 1891925 TI - The contributions of microvascular surgery to emergency hand surgery. AB - Microvascular surgery has revolutionized the field of emergency hand surgery in the areas of replantation and microvascular transplantation. Amputated parts from as small as a distal phalanx to the entire extremity can now be successfully replanted and unreplanted, or missing parts can be restored and reconstructed with immediate microvascular transplants (MVTs). MVTs can be used to cover exposed vital structures and replace missing complex parts. Part or whole digits can be reconstructed, with up to 4 toe transplants. Joints, bones, and muscles can be replaced with osteocutaneous and neuromyovascular transplants. Using the same approach for multiple replants, teams of 4 to 6 surgeons operating simulatneously and sequentially around the clock can accomplish multiple microvascular transplants in the acute setting. The classical principle of hand surgery, "preserve length and function", can now be modified to "restore length and function." PMID- 1891926 TI - Reconstruction of the thumb and digit by toe to hand transplantation. AB - Since the rapid development of microsurgery it is feasible to replant most severed thumbs and digits. In certain patients, however, the trauma is so severe that replantation cannot be performed, such as crush or burst injuries where the amputated part is badly smashed or broken into pieces. There are many methods used to reconstruct amputated thumbs or digits. In our hospital reconstruction of the thumb is accomplished by second toe transplantation, nail flap of the great toe transplantation and bone graft, and nail flap of the great toe and skeleton from the second toe transplantation. Reconstruction of fingers is undertaken through second toe transplantation and second and third toe transplantation. After total loss of the hand, double second toe transplant is used for reconstruction. PMID- 1891927 TI - Surgical opportunism in emergency hand surgery. AB - Surgical opportunism is the exploitation of circumstances at the time of surgery which will maximize the ultimate functional result. This may be an imaginative original application of surgery and regularly demands a degree of lateral thinking to visualize the opportunity. It involves particularly the careful appraisal of all damaged or amputated tissues and assessment as to their potential usefulness. Microvascular anastomosis greatly broadens the scope of opportunism in emergency hand surgery. PMID- 1891928 TI - Classification and evaluation of the functional results of replanted parts of the hand at the Prince of Wales Hospital and the Prince of Wales Children's Hospital: 1984 to 1988. AB - This paper describes a simple method of classification and evaluation of the functional results of replanted and revascularized parts in the hand. The results are presented in graphic form and have been analyzed to correlate various factors: injured part, cause, and zone (level) of injury. The type of injury, ischemic time and age have been studied in more detail to determine their influence of the final functional result. The series contains 187 amputated and devascularized parts of the hand in 119 patients who have undergone surgery at the Prince of Wales Hospital from 1984 through 1988. The length of cold or warm ischemic times, up to 16 hours in this series, while not affecting survival of the amputated part, does adversely affect the functional result. The survival rate of replanted parts in children was significantly less favorable than in adults, but the functional results were uniformly superior. PMID- 1891929 TI - Primary flexor tendon repair: surgical techniques based on the anatomy and biology of the flexor tendon system. AB - The anatomy, biology and bio-mechanics of the flexor tendon system demand a precise approach to flexor tendon repair. Within the fibroosseous canal, the synovial fluid and a complex intratendinous vascular network provide nutrition for intrinsic flexor tendon healing. Retention of the synovial sheath theoretically maintains an enclosed tendon/tendon sheat environment in which the tendon repair is bathed in synovial fluid, and may glide within a smooth tunnel. The preservation of the intricate double tendon inter-relationship and the annular pulley system is vital to the efficiency of finger flexion. This review details surgical and postoperative techniques aimed at restoring the normal anatomy and providing optimal conditions for the return of flexor tendon function. PMID- 1891930 TI - The use of flaps in the treatment of fingertip injuries. AB - Fingertip injuries constitute a large portion of the traumatic injuries sustained to the hand and are frequently associated with significant disability for the patient. While many methods are available for the treatment of such injuries, quite often only certain procedures are appropriate for a particular digit in any given patient. The use of flaps in such instances provides an important tool for coverage of the exposed fingertip bone when more simple measures are inadequate. Herein follows a discussion of the indications and potential pitfalls for a variety of flaps which may be employed in the treatment of fingertip injuries. PMID- 1891931 TI - Acute rotary dislocation of the scaphoid: a new technique of repair using Herbert screw fixation across the scapho-lunate joint. AB - Acute rotary dislocation of the scaphoid is commonly misdiagnosed and, if untreated, leads to progressive osteoarthritis of the wrist. The diagnosis requires a high degree of awareness and an understanding of the pathomechanics of the injury. To date, no single method of treatment has been shown to produce consistently satisfactory results. This paper presents a new surgical technique involving open reduction and reattachment of the ligament to the bone, combined with Herbert screw fixation across the scapho-lunate joint. The screw is normally left in situ for 12-18 months, allowing sufficient time for ligament healing and restoration of carpal stability. Using this technique early postoperative wrist motion is possible. Although excellent results have been achieved in the majority of cases, a few patients have developed increasing carpal collapse deformity in spite of adequate internal fixation, presumably due to inadequacy of the volar carpal ligaments. However, although the technique is a demanding one, the Herbert bone screw appears to offer significant advantages over standard Kirschner wire fixation in the treatment of acute rotary dislocation of the scaphoid. PMID- 1891932 TI - Emergency repair and reconstruction in the severely crushed hand. AB - Crushing injuries of the hand are a common clinical problem which require judgement and assessment by an experienced hand surgeon for an optimum result. The crushed hand has to be viewed in the perspective of injury to an essential organ with its skin and contents, namely muscles, vessels, nerves, tendons, bone and joints. A poor result is often due to inadequate wound debridement, failure to identify the extent of crushing of the devitalized tissue, closure of the skin under tension in the presence of wound contamination, and complex repairs in an avascular bed. In an emergency situation, the simplest suitable procedure is preferred. Open degloving injuries, grease and paint gun injuries, and especially closed crushing, degloving injuries can be very misleading and need special attention. PMID- 1891933 TI - Replantation surgery. AB - From 1975 to 1988, replantation operations of fingers or hands were performed in 2,040 patients at the Division of Plastic and Reconstructive Surgery, Technical University Munich, Germany. The meticulous repair of blood vessels is still the most important step for a successful replantation. The liberal use of vein grafts very often makes replantations possible even in avulsion and crush injuries. The best functional results are achieved in replantations of distal finger parts, because an intact proximal interphalangeal joint and tendon apparatus guarantees almost a full range of motion. Age alone is not an exclusionary factor for replantation. Even 70 or 80 year old patients can achieve a satisfying functional result after replantation. Replantation as a matter of course is indicated in every amputation. Nevertheless, the extent of tissue damage, patient age and general health condition as well as the patient's wishes regarding a replantation have to be considered before performing a replantation. In addition, only continuous, long-term physical therapy be specialized physical therapists and the continuous postoperative attention of the surgeon ensure a satisfying result. PMID- 1891934 TI - To trim or replant: a matter of cost. AB - Many factors are involved in the decision whether to complete the amputation of an injured digit and trim the stump or to replant the amputated member. This paper compares the cost of these two treatments so that this financial aspect might be included among the many factors which influence the surgeon's decision. The cost of these treatments was separated into two aspects. First, the overall cost of the medical and surgical expenses was calculated. Second, the cost which the Israeli social security granted the injured worker due to the disability was calculated. By comparing the total surgical and medical costs of amputations and replantations, trimming is far less expensive than replantation. In the long run, the compensation the insurer owes the disabled trimmed patient is far higher than the compensation given to those who were successfully replanted, provided the injured worker has a certain number of working years to retirement and has a yearly income of a certain level. Thus, in most cases, replantation is recommended from the cost benefit aspect. PMID- 1891935 TI - Advances in peripheral nerve repair in emergency surgery of the hand. AB - The development of microsurgical techniques has changed the surgical treatment of severe hand injuries over the last 25 years. Not only has the repair of vessels by microvascular surgery brought new possibilities of treatment, but the results in repair or peripheral nerves have been improved by the use of new microsurgical techniques, such as perineural suture and interfascicular nerve grafts. The use of vascularized nerve grafts in multiple digit amputations has been a further new idea in emergency hand surgery. The operative treatment of lesions of the brachial plexus has become possible. Nevertheless, the traditional secondary operations such as tendon and muscle transfers are necessary in order to reach an optimal functional reconstruction following nerve injuries. PMID- 1891936 TI - Interposed muscle grafts in nerve repair in the hand: an experimental basis for future clinical use. AB - Repair of digital nerves and the larger nerves supplying the hand is a common clinical problem. A number of options exist for either direct repair or reconstitution using an interposed graft. Each of these options is associated with a set of problems peculiar to itself and to nerve repair in general. The heterogeneity of nerve injuries and of the various methods of repair and assessment has not led to the establishment of clear comparisons and guidelines for surgical intervention. Recently, freeze-thawed coaxially aligned skeletal muscle autografts have been added to the list of available grafting techniques. The present article discusses the genesis of the muscle graft technique and examines steps which have been taken to elucidate its performance in controlled laboratory conditions. The extent to which these experimental observations provide a foundation for the clinical use of muscle grafts is discussed. PMID- 1891937 TI - Clinical and pathologic properties of small differentiated carcinomas of the thyroid gland. AB - Ninety-one small differentiated thyroid carcinomas less than 10 mm in size treated during the last 33 years were subjected to clinical study. In 44 of the 91 cases, tumor was found incidentally at surgery, while in the remaining 47 a thyroid mass was palpable before operation. A preoperative diagnosis of carcinoma could not be made in nodules less than 5 mm in size. Ultrasonographic examination is now extending the limits of exact diagnosis. Metastasis was found in 16 of 33 patients who had lymph nodes dissected. Metastatic lymph nodes were distributed in the same sites as those with thyroid carcinomas larger than 10 mm. Pathologic examination was carried out in 108 small carcinomas including cases from an affiliated hospital. Histologically, all of them were papillary or follicular carcinomas. The growth pattern of the tumors was divided into 5 groups: 23 were nonencapsulated sclerosing type, 29 encapsulated type without capsule invasion, 48 encapsulated type with capsule invasion, 4 the infiltrative type, and 4 the round type. Lymph node metastasis and intraglandular dissemination were found most frequently in the infiltrative type, followed by the encapsulated type with invasion. The results suggest the necessity of lymph node dissection and lobectomy for patients with these histological types of small carcinomas who had only local removal of the tumor. PMID- 1891938 TI - Open approach in pancreatic and infected pancreatic necrosis: laparostomies and preplanned revisions. AB - One hundred and two patients with acute necrotizing pancreatitis were treated in accordance with a combined regimen of necrosectomy, open drainage by laparostomies, and repeated re-explorations. The severity of pancreatitis was assessed by the APACHE II score (median 15 on admission). Eighty-seven (85%) patients were classified as having infected pancreatic necrosis and only 15 (15%) as having pancreatic necrosis. Overall, 36 (35%) patients died, most of multiple organ failure. Survival was significantly impaired by bacterial contamination of pancreatic necrosis (p = 0.008), bacteremia (p = 0.0001) and infected bronchial secretions (p = 0.05). The mortality rate was reduced from 53% to 28% by changing the regimen of re-explorations from on demand to regular 48 hour intervals. Despite the fact that open packing was associated with a high frequency of gastrointestinal fistulas (30%), this concept seems to be a successful and recommendable approach in the therapy of pancreatic and infected pancreatic necrosis. PMID- 1891939 TI - The single-layer continuous suture for gastric anastomosis. AB - The single-layer continuous suture technique has proven to be safe for all intestinal anastomoses of intraperitoneal small and large bowel segments. Since 1985, this technique has also been increasingly applied for gastroduodenostomy and gastrojejunostomy following partial gastrectomy. Through December 1989, we performed 96 gastroenteric anastomoses with the single-layer continuous suture technique. This accounts for 64% of all partial gastrectomies performed between 1985 and 1989. The technique was applied in 89.5% of the gastroenteric anastomoses during 1988 and 1989. The rate of complications after gastroenteric single-layer continuous suture technique was low; 2.1% clinical leakage was found, always in patients with perforated ulcer and peritonitis. We conclude that the single-layer continuous suture technique for gastroenteric anastomosis is safe, simple, easy to perform, quick and reliable. PMID- 1891940 TI - The diagnostic challenge of postoperative acute appendicitis. AB - During the period 1979 to 1989, 0.1% of all cases of acute appendicitis at our institution occurred soon after another operative procedure. The interval between primary operation and appendectomy was 5 to 31 days (mean, 14 days). Signs and symptoms did not differ from those of classical acute appendicitis. Duration of symptoms ranged from 12 hours to 8 days (mean, 2.4 days). Perforation was present in 3 patients, suppurative appendicitis in 1 patient, and acute inflammation in 4 patients. Two of the perforations were associated with abscess formation. Morbidity related to the appendiceal condition included hepatic abscesses, septic shock, and prolonged ileus. There was no mortality. Hospitalization ranged from 6 to 80 days (mean, 12.5 days). PMID- 1891941 TI - Hyperthermo-chemotherapy combined with cytoreductive surgery for the treatment of gastric cancer with peritoneal dissemination. AB - Continuous hyperthermic peritoneal perfusion (CHPP) with anticancer agents (mitomycin C and cisplatin) in warm saline was performed in patients with peritoneal dissemination of gastric cancer following resection of the primary lesion. The effect of CHPP was examined by a second-look operation. This study includes 41 cases of gastric cancer with peritoneal dissemination but without liver metastasis treated during the past 6 years. The overall median survival was 14.6 months to 64.2 months from CHPP to death and the 3-year survival rate was 28.5%. Second look surgery revealed a remarkable diminution in the degree of peritoneal dissemination in 7 (50%) of 14 patients with disappearance of ascites after only one course of CHPP in 7 (77.8%) of 9 patients. Long-term 3 year survival was noted in 4 (9.8%) patients on CHPP. Side effects were renal insufficiency in 2 (5%) patients, leukopenia in 2 (5%) patients, and perforation of the small intestine in 1 (2%) patient. These results suggest the effectiveness of CHPP in the treatment of gastric cancer with peritoneal dissemination. PMID- 1891942 TI - Secondary hyperparathyroidism: diagnosis of site of recurrence. AB - Persistent or recurrent hyperparathyroidism after total parathyroidectomy with forearm implant may be caused by hyperplastic grafted tissue, residual parathyroid tissue left in the neck or the presence of a supernumerary gland not found during surgery. A correct assessment of graft function is needed to localize the source of hormone excess and to avoid an unnecessary neck reoperation in cases of graft dependent hyperparathyroidism. In 12 patients with relapsing hyperparathyroidism after total parathyroidectomy with forearm implant, total ischemic blockade of the arm bearing the parathyroid graft produced a "transitory implantectomy" with a significant reduction of serum levels of intact PTH in those with graft hyperfunction. In 6 patients with proved supernumerary glands, total ischemia of the graft was not followed by significant changes in intact PTH. Hyperparathyroidism was reversed after surgical resection of the parathyroid implants in the 6 patients with positive responses to the ischemic maneuver. A repeat neck reoperation removing cervical or mediastinal supernumerary glands was followed by control of recurrent hyperparathyroidism in the 6 patients with a negative response to the ischemic blockade. Total ischemic blockade of the arm bearing the parathyroid graft is a valuable method for a correct assessment of graft function after total parathyroidectomy with forearm autotransplantation. PMID- 1891944 TI - Adenocarcinoma of the stomach: a review of 35 years and 1,710 cases. PMID- 1891943 TI - Accuracy of intraoperative ultrasonography in diagnosing liver metastasis from colorectal cancer: evaluation with postoperative follow-up results. AB - The accuracy of intraoperative ultrasonography in diagnosing liver metastasis was evaluated at the time of surgery and at follow-up in 189 patients with colorectal cancers. Evaluation at the time of operation revealed that the sensitivity of intraoperative ultrasonography (93.3%) was significantly (p less than 0.0001) higher than that of preoperative ultrasonography (41.3%), conventional computed tomography (47.1%), and surgical exploration (66.3%). Twenty-two of 104 metastatic liver tumors were detected solely by intraoperative ultrasonography in 18 patients (9.5% of total patients). These 22 tumors were small in size (4 x 4 mm to 15 x 18 mm) and nonpalpable during operation. During the postoperative follow-up period of 18 months or more (mean 35.6 months, median 37.1 months) after colorectal surgery, liver metastases that were unrecognized during surgery appeared in 13 (6.9%) patients. Re-evaluation based on these follow-up results indicated that the sensitivity of intraoperative ultrasonography decreased to 82.3%, which was still significantly (p less than 0.0005) better than that of other methods. Intraoperative ultrasonography was capable of identifying 18 of 31 (58.1%) patients in whom liver metastases were otherwise unrecognized at the time of operation. Intraoperative ultrasonography is more accurate in diagnosing liver metastasis than traditional screening methods, and may have a beneficial impact on the management of colorectal cancer. PMID- 1891945 TI - Changing trends in surgery for acute cholecystitis. PMID- 1891946 TI - The potential for the elimination of measles in the modern age. PMID- 1891947 TI - Music therapy: a means of reducing anxiety in the myocardial infarction patient. PMID- 1891948 TI - Family protective thinking about cardiac events: nursing interventions to promote maintenance of family health behaviors. PMID- 1891949 TI - The Wisconsin Farmers' Cancer Control Project. PMID- 1891950 TI - Epidemiology of Haemophilus influenzae type b disease in Australia and New Zealand. AB - The epidemiology of infection due to Haemophilus influenzae type b (Hib) varies in different groups of Australian and New Zealand children. In most populations the annual case attack rate is approximately 40-60 per 100,000 children under 5 years of age and epiglottitis accounts for a relatively high but variable proportion of cases, which partly depends on case definition. Overall, nearly 50% of cases occur in children over 2 years of age. Among Aboriginal children in the Northern Territory, the epidemiology is strikingly different. The annual case attack rate is approximately 450 per 100,000 children under 5 years and varies in different geographical areas. Most cases occur in the first year of life (40% at less than 6 months) and epiglottitis is rare. The case attack rate in non Aboriginal children in the Northern Territory (88 per 100,000) is significantly less than in Aboriginal children but higher than elsewhere. The differences between Maori and Caucasian children in New Zealand are less marked. Different immunization strategies may be required for children in different populations within Australia and New Zealand. PMID- 1891951 TI - Experience in Finland with Haemophilus influenzae type b vaccines. AB - The importance of Haemophilus influenzae type b (Hib) as the leading cause of bacteraemic infections in children was recognized in the early 1970s in Finland. An efficacy trial with the capsular polysaccharide vaccine demonstrated the efficacy of this first generation vaccine, but only from ages 18-24 months onwards. For this reason, since 1983 new polysaccharide-protein conjugate vaccines (PRP-D, HbOC, and PRP-T) have been extensively tested. These studies have shown that conjugate vaccines are immunogenic in early infancy and are capable of generating a lasting immunological memory. A second Hib vaccine efficacy trial in 1986-1987 showed that the conjugate vaccine (PRP-D) was 90% efficacious after the primary immunization series at 3, 4 and 6 months. After a booster dose at 14-18 months, no failure cases have occurred during the follow-up period. The same level of protection seems to be true also in a subsequent trial, where two Hib conjugate vaccines (PRP-D or HbOC) were given at 4, 6 and 14-18 months. These vaccinations have led to a significant decline in the number of invasive Hib infections in young children. PMID- 1891952 TI - Prevention of invasive Haemophilus influenzae type b disease: lessons from vaccine efficacy trials. AB - To assess vaccines, multiple laboratory investigations and immunogenicity studies are conducted but the ultimate tests of the effectiveness of a vaccine are field trials that evaluate disease prevention. Immunogenicity studies are often used as a surrogate for protection, but it is often difficult to determine precisely the level of antibody needed for protection and it is not always clear what immunologic factors most determine protection. However, efficacy trials are difficult to conduct well and there are only a limited number of ways to perform such studies. Nonetheless, the results of efficacy studies are essential for the appropriate selection of the best Hib vaccines and to establish recommendations for optimal use. The first Hib vaccine, the PRP (polyribosylribitol phosphate) polysaccharide vaccine, was shown by several efficacy studies to have no protective efficacy in young infants, and to have only limited, if any, efficacy in older children. The first Hib polysaccharide conjugate vaccine, PRP-D, is more immunogenic and provides better protection than PRP in older children (greater than 18 months of age), but it has limitations in both immunogenicity and protective efficacy when given to children younger than 6 months of age. Newer, more promising, Hib conjugate vaccines are now available, and include HbOC, PRP OMP, and PRP-T vaccines. Each is currently being evaluated in field trials to evaluate protective efficacy and the methods and results of these trials will be reviewed. The control of invasive Hib disease worldwide will depend upon the appropriate application of knowledge derived from these field trials. PMID- 1891953 TI - Biological activity of Hib conjugates. AB - Haemophilus influenzae type b (Hib) conjugate vaccines dramatically improve the immunogenicity against the capsular polysaccharide (PRP) of Hib. A new Hib conjugate, PedvaxHIB, is shown to be immunogenic in infant rhesus monkeys. The monkey model appears to correlate well with the immunogenicity of PedvaxHIB in human clinical studies. Not all commercial Hib conjugates are immunogenic in the monkey model. The data from the priming study indicate that HibTITER is not immunogenic in an immune system naive to diphtheria toxoid, such as the infant rhesus monkey. The role of diphtheria toxoid in the immunogenicity of HibTITER in human infants should be studied. PMID- 1891954 TI - Comparative immunogenicity of Haemophilus influenzae type b polysaccharide protein conjugate vaccines. AB - There are only minor differences in the immunogenicity of the three Haemophilus b polysaccharide-protein conjugate vaccines licensed in the US when tested in children 17 to 19 months of age. In contrast, there are much greater differences in immunogenicity in 2-month-old infants. At this age, a single dose of PRP-OMPC evokes a strong primary antibody response, whereas repeated doses of HbOC or PRP D are required to evoke an antibody response. These differences in immunogenicity are noteworthy, but they are not necessarily correlated with differences in the ability of different conjugate vaccines to confer protection against disease. Vaccination with all three of the conjugate vaccines primes infants for the ability to make a booster antibody response to reimmunization with unconjugated PRP vaccine and, possibly, to exposure to the encapsulated bacteria. Although unproven, this priming may be sufficient to confer protection against disease even in the absence of a 'protective' level of serum antibody. PMID- 1891955 TI - Strategies for immunization against invasive Haemophilus influenzae type b infection. AB - Available data on the immunogenicity, safety and efficacy of Hib conjugate vaccines are encouraging and the prospects for having a means to control invasive Hib disease are good. Most of the third generation Hib vaccines seem to prevent invasive Hib disease at a level of efficacy that motivates worldwide mass immunization of infants. The peak incidence of Hib meningitis occurs before the age of 1 year in most industrialized countries and the most desirable time to start vaccination against Hib is at 2-3 months of age. In many countries a Hib conjugate vaccine may ideally be coordinated with the DTP immunization programme. In non-industrialized countries the peak incidence of Hib meningitis occurs earlier than in industrialized countries, which means that in these areas immunization against Hib meningitis should start earlier, for instance at 6 weeks when the first DTP vaccine injection is given in many countries. PMID- 1891956 TI - Clinical experience with PedvaxHIB, a conjugate vaccine of Haemophilus influenzae type b polysaccharide--Neisseria meningitidis outer membrane protein. AB - PedvaxHIB, a Haemophilus influenzae type b (Hib) conjugate vaccine composed of Hib capsular polysaccharide covalently bound to an outer membrane protein complex of Neisseria meningitidis serogroup B, was evaluated for immunogenicity and safety in infants and children 2 months of age and older. A significant and consistent antibody response was seen after a single dose of the vaccine in all age groups, including infants as young as 2 months of age. In addition, the vaccine elicited a good booster response when given at 12 to 17 months of age. Subjects from diverse subpopulations, including those with impaired antibody response to Hib polysaccharide vaccines, showed a significant response to vaccination. The vaccine was well tolerated when administered alone or concurrently with other paediatric vaccines. A protective efficacy study, recently completed, has shown the vaccine to be highly effective in 2-month-old infants. PMID- 1891958 TI - Changes in cell gene expression in human leukemic cells persistently infected with vaccinia virus. AB - Persistent viral infections in vitro are useful systems to study the coevolution of virus and cell populations. Persistent infection of mouse Friend erythroleukemic cells (FEL) with vaccinia virus results in profound changes of the virus as well as of the cells. To investigate phenotypic changes of other cell types, we have established a persistent infection with vaccinia virus in a human leukemic cell line (K562). This cell line can be induced to differentiate along the erythroid pathway synthesizing embryonic and fetal globins, thus providing a system in which specific genes can be stimulated. After serial passage, the persistently infected cells (K562vac) became spontaneously differentiated, as shown by the increase in the number of cells producing hemoglobin (benzidine positive cells), and resistant to superinfection. These phenotypic changes of the cells were not accompanied by changes in the viral population. Hybridization of cellular RNA with cloned embryonic and fetal globin genes indicated that uninduced K562 cells do not express these genes, whereas cells induced by hemin or butyrate express G gamma (fetal globin) epsilon and zeta (embryonic globins) genes. By contrast vaccinia infected cells spontaneously express the G gamma gene. These results demonstrate that persistent infection with vaccinia virus elicited phenotypic changes in the infected cell population; in this case the constitutive expression of fetal hemoglobin. PMID- 1891957 TI - World-wide epidemiology of Haemophilus influenzae meningitis; industrialized versus non-industrialized countries. AB - The epidemiology of Haemophilus influenzae meningitis in non-industrialized areas shows considerable differences from that in the industrialized world. The incidence rates among Alaskan Eskimos, Navaho and White Mountain Indians, Australian Aboriginals and among populations in Africa such as Gambians and Senegalese are three- to fourfold higher than those in the USA and up to ten times higher than those in Europe. The peak age in populations with a high incidence is around 5 to 6 months of age compared to 9 months of age in other countries. The case fatality rate (CFR) is not related to the state of industrialization but seems to be more dependent on the accessibility of health care facilities. Africa the CFR is about ten times higher than that seen elsewhere. Apart from other dissimilarities such as the pattern of serotypes causing disease and the transmission rate, the epidemiology of Hib disease is sufficiently different from industrialized areas that it demands a thorough testing of a conjugated Hib vaccine before it can be introduced on a large scale in populations in non-industralized areas. PMID- 1891959 TI - Synthesis of the virus-specified tubules of epizootic haemorrhagic disease virus using a baculovirus expression system. AB - The formation of virus-specific tubules is one of the most characteristic features in the orbivirus infection cycle, yet little is known about their role in virus replication. The tubuli are composed of a major nonstructural protein, NS1. We have investigated the expression of the NS1-encoding gene of epizootic haemorrhagic disease virus serotype 2 (Alberta-strain) by producing a recombinant Autographa californica nuclear polyhedrosis virus (AcNPV). Prior to cloning in the baculovirus transfer vector, pAcYM1 and cotransfection with AcNPV DNA, the NS1 gene was tailored by means of a polymerase chain reaction method to remove G/C tails. The baculovirus recombinant, AcNPV-EHDV2 NS1, expressed large amounts of a 55 K protein which could be purified by sucrose gradient sedimentation as a tubular complex. It appeared that the tubules could break up into 50 nm diameter circular units, which in turn were composed of approximately 16 subunits. The circular units appeared to be hollow and stacked on top of one another (100 units/micron tubule length), giving the tubules a segmented, ladderlike appearance. A large excess of EHDV2-specific tubuli could also be demonstrated in AcNPV-EHDV2 NS1-infected Spodoptera frugiperda cells by electron microscopic examination of thin sections. With pulse-labelling experiments it was shown that, regardless of the level of NS1 expression, the majority of NS1 synthesized in a 30 min period could only be recovered in a particulate form. PMID- 1891960 TI - Differential suppression of host cell protein synthesis and mRNA levels in herpes simplex virus-infected endothelial cells. AB - Earlier studies from this laboratory have shown that infection of vascular cells with herpes simplex virus 1 or 2 (HSV-1, HSV-2) results in the differential suppression of extracellular matrix proteins including fibronectin (FN), type IV collagen, thrombospondin (TSP) and Factor VIII von Willebrand protein. The present study was designed to determine whether a correlation exists between suppression of synthesis of specific proteins and their mRNA levels. We have measured the steady-state levels of mRNAs for several extracellular matrix proteins (type IV collagen, FN and TSP) and two intracellular proteins (actin and tubulin) in human endothelial cells (EC) following HSV-1 infection. The results show that during the first 5 h post-infection, when there is a rapid decrease in the synthesis of extracellular matrix proteins, the steady-state levels of the corresponding mRNAs remain relatively high, but progressively decline to levels of less than 20% by 13 h post-infection. These findings suggest that in the early hours post-infection there is an alteration in the translatability of the hybridizable message followed by degradation in the later hours. PMID- 1891961 TI - The nucleotide and predicted amino acid sequence of the attachment protein of canine distemper virus. AB - The nucleotide sequence of the gene coding for the attachment protein of the Convac strain of the canine distemper virus (CDV), corresponding to the haemagglutinin (H) gene of measles virus was determined using a mRNA-derived cDNA clone and genomic viral RNA. The mRNA transcribed from the CDV H gene is 1944 nucleotides long excluding the polyadenylated tail. Only one long open reading frame was found comprising nucleotides 21-1841. The predicted protein has a single hydrophobic region which can serve as a membrane anchoring domain. The deduced 607 amino acids would code for a protein of 68,247 Da, to be compared with an approximate protein molecular weight in SDS-PAGE of the glycosylated protein, which is 85,000 Da. The CDV H protein exhibited seven potential N-linked glycosylation sites. These were concentrated to the carboxyterminal part of the CDV H protein and differed markedly from measles virus (MV) and rinderpest virus (RPV) where the potential sites were mostly conserved and located in the amino terminal half of the proteins. In spite of the differences in amino acid composition of these three H proteins their hydrophilicity/hydrophobicity plots were closely similar with the major hydrophobic region at an identical location. All the 12 cysteine residues found in the CDV H protein were conserved in MV and RPV. The amino acid homology between CDV and MV H protein was 37% and between CDV and RPV H protein 38%. The fact that the corresponding homology between the MV and RPV proteins is almost 60% shows that the evolutionary separation between CDV and RPV occurred at a much earlier time than the separation between RPV and MV. PMID- 1891962 TI - Complete nucleotide sequence of a Latin-American isolate of potato virus X. PMID- 1891963 TI - Viral sequence data. PMID- 1891964 TI - The dual role--educator and lobbyist. PMID- 1891965 TI - Reducing the need for intubation in plastic surgery. PMID- 1891966 TI - The standard of care. PMID- 1891967 TI - Fetal injury and abortion associated with occupational exposure to inhaled anesthetics. AB - While the actual risk associated with occupational exposure to inhaled anesthetics has not precisely been defined, a growing body of data has accumulated so that we may begin to make certain valid inferences. Published studies of the teratogenic, mutagenic and carcinogenic effects of exposure to nitrous oxide and isoflurane suggest that a causal role of these inhaled agents appears to be very low or nonexistent. PMID- 1891968 TI - Faculty positions as a career choice for professionals--Part II. AB - This is the second part of a two-part article designed to identify "why professionals choose or do not choose faculty positions." The first article reviewed the methodology and the results as they applied to the demographic data. This was published in the June 1991 issue of the AANA Journal. This article reviews the results as they apply to life cycle and certain intrinsic and extrinsic factors of the respondents. The respondents were CRNAs who had graduate degrees, or were faculty in nursing education, faculty in higher education, or nursing service personnel. The article also covers additional recommendations made by the researchers for future studies. The results showed that 71% of the CRNA faculty intended to remain in academia for the next 5 years and 75% for the next 10 years. Ninety percent of the CRNA faculty indicated they would recommend a position in teaching to others. Intrinsic factors, such as the ability to use their knowledge and opportunity to teach were important to CRNA faculty as an influence to become faculty members. Extrinsic factors of salary, fringe benefits, and the cost of malpractice insurance were among those items identified by CRNA faculty as reasons why they would not become faculty members. It is hoped that this study will assist nurse anesthesia programs, universities and colleges in faculty recruitment activities. The information was presented by the authors at the Assembly of School Faculty Meeting held in Tampa, Florida, in February 1991. PMID- 1891969 TI - Certification: past, present and future implications. Report of the National Commission on Nurse Anesthesia Education. AB - In 1942, the National Association of Nurse Anesthetists established a voluntary certification program to safeguard the interests of surgeons, hospitals and the public. Prerequisites for certification included minimum training standards, a valid nursing license and successful completion of a national certification examination. In 1975, the Council on Certification of Nurse Anesthetists was established as an autonomous decision-making body. Certification for nurse anesthetists is now recognized in two-thirds of the states and required by most employers--a factor that makes it vital to establish the job-relatedness of the examination. An innovative and responsible certification process will continue to be needed to address health care issues and advances in testing. PMID- 1891970 TI - Anesthetic management for anterior mediastinal mass and mediastinoscopy: a case study. AB - A 27-year-old white male was scheduled for a mediastinoscopy of an anterior mediastinal mass. The patient was induced with thiopental and succinylcholine, in anticipation of possible difficulty managing the airway. There was no distortion of the airway, and he was easily intubated with a No. 8.5 anode tube and given 20 mg of atracurium. The extent of tumor growth was greater than expected and, as a result, biopsies of the neck were taken without the need for mediastinoscopy. The atracurium was reversed with atropine and edrophonium. Although respirations were being assisted, the SaO2 decreased significantly, and end-tidal CO2 was greatly increased. When the drapes were removed, the patient was found to be cyanotic, with vein distention in the neck and upper extremities. All anesthetic agents were discontinued, the patient was hyperventilated with 100% oxygen, 100 mg of lidocaine was given for coughing and breath-holding, and the patient was placed in the reverse Trendelenburg position. The SaO2 then increased, and the end-tidal CO2 decreased. Respirations were spontaneous, and the patient could be extubated. The probable cause of this episode was obstruction of the superior vena cava by the anterior mediastinal mass. When the muscle relaxant was reversed, the increase in intrathoracic pressure caused the mass to compress the superior vena cava. The compression was released by placing the patient in a reverse Trendelenburg position, which caused the mass to shift. In addition to superior vena cava compression, other complications of anterior mediastinal masses include airway obstruction, distortion of anatomy, impaired cerebral circulation and myasthenic syndrome.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1891971 TI - AANA Journal course. 15: new technologies in anesthesia: update for nurse anesthetists--continuous spinal anesthesia. AB - The production of microcatheters small enough to be threaded through 22- to 26 gauge spinal needles has focused renewed attention on the technique of continuous spinal anesthesia. This technique has a specific combination of advantages which cannot be duplicated by any other method of regional blockade. The most important of these advantages is that sensory blockade can be produced quickly and precisely with small doses of local anesthetic, that the duration of anesthesia can be extended indefinitely, and that recovery is rapid when short-acting local anesthetics are used. Inadequate anesthesia, failure to thread the catheter, catheter breakage, prolonged neurologic deficits (e.g., cauda equina syndrome), and postdural puncture headache are uncommon complications. This installment of the AANA Journal Course will explore the latest developments regarding this emerging regional technique. PMID- 1891972 TI - Sensory and motor reflex control of nasal mucosal blood flow and secretion; clinical implications in non-allergic nasal hyperreactivity. AB - 1. Co-localization of SP and CGRP was observed in a dense intraepithelial and perivascular network of capsaicin-sensitive sensory nerves in the nasal mucosa of different species, including man. The morphological similarity in the distribution of these nerves among various experimental animals and man indicates that animal experimental data may be used for the understanding of sensory mechanisms in the human nasal mucosa. 2. Release of CGRP into the venous effluent of the nasal mucosa in parallel with vasodilatation was demonstrated in vivo upon antidromic stimulation of the maxillary division of the trigeminal nerve or local i.a. capsaicin injection. 3. Infusion of capsaicin induced concentration dependent increase in arterial, venous and superficial blood flow as well as V in the pig nasal mucosa. Exogenous SP, CGRP and VIP displayed concentration dependent, but partly separate, vasodilatory profiles in the nasal mucosa. SP was more potent regarding maximal blood flow increase, whereas the vasodilatation induced by CGRP infusion was more long-lasting on an equimolar basis. Although VIP caused an increase in ABF and VBF as well as V, the LDF signal (i.e. superficial blood flow) was decreased, possibly due to a stealing phenomenon. 4. Local i.a. capsaicin infusion induced a bilateral chlorisondamine-sensitive atropine-resistant vasodilatation. However, i.a. capsaicin in higher doses also induced a chlorisondamine-resistant vasodilatation in the superficial vascular compartment of the nasal mucosa, presumably via the release of sensory neuropeptides. Thus, the vasodilatory effect of capsaicin may be due to a complex interaction of local effects on the sensory nerve terminals close to blood vessels in the nasal mucosa and a main parasympathetic central reflex. 5. Capsaicin, but not nicotine, induced a concentration dependent increase in irritation or pain upon local application to the human nasal mucosa. Since both agents evoked secretion, this indicates that capsaicin and nicotine activate different populations of sensory neurons. Local application onto the nasal mucosa of capsaicin and nicotine as well as metacholine induced a concentration dependent muscarinic antagonist sensitive increase in the secretory response. The capsaicin or nicotine-induced secretion was bilateral and could be markedly reduced by combined pretreatment with a local anaesthetic and a vasoconstrictor. Our findings suggest that the secretory effect of capsaicin and nicotine in the human nasal mucosa is mediated via a central parasympathetic reflex arc with a final muscarinic receptor mechanism. No clear-cut contribution seemed to be exerted by locally released tachykinins and CGRP as direct trigger substances for the secretory response to capsaicin.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1891973 TI - Protective effects of calmodulin antagonists (trifluoperazine and W-7) on hypothermic ischemic rat hearts. AB - The cardioprotective effect of calmodulin antagonists, trifluoperazine (TFP) and N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide (W-7) was examined on the isolated rat heart exposed to hypothermic and ischemic conditions by measuring distribution of lysosomal enzymes in myocardial cells, and leakage of creatine kinase (CK) during reperfusion and postischemic recovery in myocardial systolic function. Experimental hearts were infused with 20 degrees C Krebs-Henseleit bicarbonate buffer (KHB) or KHB containing TFP or W-7 for 2min every 30min during hypothermic ischemia. After ischemia for 120min at 20 degrees C, rat hearts were reperfused at 37 degrees C for 30min. TFP and W-7 improved functional recovery and prevented CK release. In TFP treated hearts, leakage of lysosomal enzymes was reduced significantly, whereas stabilization of lysosomes by W-7 did not occur. These results suggest that calcium-calmodulin dependent enzymes may play an important role in the development of cellular damage of the myocardium during hypothermic ischemia, although levels of leakage of lysosomal enzymes may be unreliable predictors of functional recovery after hypothermic ischemia. PMID- 1891974 TI - A monoclonal antibody (OPT1) to T cells which is available for paraffin-embedded materials. AB - A monoclonal antibody (MAb), OPT1, reactive with T cells in formalin-fixed, paraffin-embedded tissue sections, has been identified through immunization with activated T cells from peripheral blood lymphocytes (PBL). The antibody is an IgG1 antibody as demonstrated by the Ouchterlony technique. By cytofluorometric analysis, almost all CD3+ lymphocytes and only a few CD20+ lymphocytes of peripheral blood expressed the OPT1 antigen. Nonhematolymphoid cell lines were negative for OPT1 by the immunoperoxidase staining using acetone-fixed cell lines. On the contrary, peripheral T cells, cells of two T cell lines out of four and a part of the cells of one B cell line out of two were positive for OPT1. The immunoperoxidase staining of paraffin-embedded tissue sections revealed that most of lymphocytes in T cell areas of lymph nodes expressed OPT1 antigen. Some lymphocytes in both cortex and medulla of the thymus and erythroid precursors of the bone marrow were OPT1+. In the malignant lymphoma series, approximately 90% of T cell lymphomas and 6% of B cell lymphomas reacted with OPT1. None of the Reed-Sternberg cells nor Hodgkin cells in Hodgkin's disease were positive. Consequently, OPT1 may be useful for the diagnosis and study of malignant lymphomas and other related lesions. PMID- 1891975 TI - Immunohistochemical characterization of the lymphocyte and the immunoglobulin containing cell in the epithelium and the lamina propria of normal human intestines. AB - In order to clarify difference of the mucosal immunity in various sites of normal large and small intestines, we studied the population of lymphocyte subsets and immunoglobulin (Ig)-containing cells in situ in biopsy specimens taken from various sites (ascending colon, sigmoid colon and rectum) of the large intestine and from the duodenum using an immunohistochemical method. Monoclonal antibodies against pan-T (Leu 1), cytotoxic/suppressor T (Leu2a), helper/inducer T (Leu3a), suppressor T (Leu15) and natural killer/K (Leu7) cells, and polyclonal antibodies to human IgG, IgA and IgM were used. In the duodenum, intraepithelial lymphocytes (IELs) were more prominent than in the large intestine. Immunoelectron microscopic observation revealed that some Leu2a+ IELs possessed pseudopods extending into intestinal epithelial cells, indicating that some IELs belong to the cytotoxic T cell subset. Leu7+ IELs were scarcely observed and Leu7+/Leu1+ ratio was higher in the large intestine than in the duodenum. Furthermore, the number of Leu7+ cells were more in the distal than the proximal colon. In the lamina propria Ig-containing cells tended to be fewer in the rectum than in the duodenum and the proximal colon. Our findings may suggest the variation of local immune responses and the difference of assigned immunological functions among the various sites of the intestines. PMID- 1891976 TI - Prognostic factors of peripheral T-cell lymphoma (PTL): statistical analysis on 30 patients. AB - Peripheral T-cell lymphoma (PTL) is a distinctive clinical entity, albeit it comprises several diseases with histologically heterogeneous diagnoses. We studied prognostic factors on 30 patients diagnosed and treated at Shikoku Cancer Center Hospital. Clinical findings and laboratory data were evaluated by statistical analysis to investigate the important factors influencing survival duration. Variables influencing survival were stage, leukemic change, bone marrow infiltration (BMI), anti-human T-lymphocyte virus-type I antibody, white blood cell count, and lactate dehydrogenase (LDH). Multivariate analysis revealed high level of LDH and positive BMI as the important factors for short survival. Histological classifications of the Working Formulation and the T-lymphoma classification by Suchi et al. were also evaluated whether these were related with prognosis. Our data revealed that there was no significant relationship between histological subtype and survival duration. The study of prognostic factors provides valuable aids for us to understand the clinical characteristics of PTL patients with various backgrounds. PMID- 1891977 TI - Gait analysis of slope walking: a study on step length, stride width, time factors and deviation in the center of pressure. AB - Determination was made of step length, stride width, time factors and deviation in the center of pressure during up- and downslope walking in 17 healthy men between the ages of 19 and 34 using a force plate. Slope inclinations were set at 3, 6, 9 and 12 degrees. At 12 degrees, walking speed, the product of step length and cadence, decreased significantly (p less than 0.01) in both up- and downslope walking. The most conspicuous phenomenon in upslope walking was in cadence. The steeper the slope, the smaller was the cadence. The most conspicuous phenomenon in downslope walking was in step length. The steeper the slope, the shorter was the step length. PMID- 1891978 TI - Studies of an aspect of renal function with the aid of dynamic CT and renogram. AB - Dynamic CT scans were conducted on 94 persons who had been randomly selected among the patients and the volunteers. The test results were used to obtain the time-density curve. A part of the subjects (20 cases) underwent the renogram examination for the comparative studies. The cortico-aortic (CA) ratio derived from the time-density curve demonstrated good correlation between the dynamic CT and the renal function (r = 0.68). When the dynamic CT studies and the renogram were compared, the vascular phase of the renogram showed strong correlation with CA ratio. Consequently the dynamic CT study the CA ratio was believed to demonstrate the renal function. PMID- 1891979 TI - Tissue concentration of doxorubicin (adriamycin) in mouse pretreated with alpha tocopherol or coenzyme Q10. AB - The tissue concentration of doxorubicin (adriamycin; ADM) and its major metabolite (aglycone I) was examined in mice pretreated with alpha-tocopherol (VE) or coenzyme Q10 (CoQ). In VE-pretreated group, the concentrations of aglycone I of the liver (1, 3 and 5 h after the administration), kidney (1 and 3h) and heart (3h) were significantly higher than those in the saline group. The clinical application of VE or CoQ concomitant with anti-tumor drugs especially ADM, requires caution. PMID- 1891980 TI - Immune regulation by tolerization in EAE and in Theiler's murine encephalomyelitis virus (TMEV) infection (1). PMID- 1891981 TI - Novel myelin glycoproteins and their possible involvement in demyelination. AB - Myelin membranes contain numerous glycoproteins, very few of which have been characterized. This article summarizes recent studies which suggest that some of these glycoproteins may be involved in pathological demyelination, by virtue either of their enzymic activity or of their antigenic properties. PMID- 1891982 TI - Immunopathological recognition of autoantigens in multiple sclerosis. AB - Although the aetiology of multiple sclerosis (MS) has not been established, circumstantial evidence points to the involvement of both cell-mediated and humoral immune responses in the formation of demyelinating lesions. In view of the current controversy regarding the reactivity of T lymphocytes from MS patients to myelin basic protein (MBP), we reassessed T cell reactivity in MS using a sensitive and specific indicator of cell-mediated immune response. No significant difference in the reactivity to MBP was observed between MS patients and healthy subjects. Interestingly, significant reactivity to MBP was detected in the control group comprising patients with other diseases. Nevertheless, our demonstration that polymorphism in T cell receptor (TcR) alpha chain are related to MS and that, in demyelinating lesions, TcR usage is limited, suggests that T cells may recognise particular epitopes of a critical antigen involved in this disease. The search for a specific MS antigen recognised by the intrathecally synthesized immunoglobulins typical of MS has so far been unsuccessful. However, recent work, which has focused more particularly onto myelin components with externally located epitopes accessible to the immune response, appears to be more promising. One such antigen, myelin-oligodendrocyte glycoprotein (MOG), is clearly a target for immune attack. Indeed, highly specific antibodies to MOG have been shown to cause demyelination not only in vivo but also in vitro, as demonstrated by our study of the demyelinating effects of a monoclonal anti-MOG antibody on aggregating fetal rat brain cell cultures.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1891983 TI - HTLV-I neurotropism. In vitro studies. AB - The human T cell leukemia lymphoma virus (HTLV-I) has been recently associated to neurological disorders. In order to investigate the interaction between this virus and the central nervous system, cells of neuroectodermic origin have been exposed to HTLV-I through an experimental in vitro model. The results revealed the presence of HTLV-I virus core protein p19 inside glial cells, after a short time exposure to a chronically infected donor cell line. This suggests a possible role of a lymphotropic retrovirus in neurological diseases. PMID- 1891984 TI - Aids dementia complex. On the relationship between HIV-1 infection, immune mediated response and myelin damage in the brain. PMID- 1891985 TI - HIV-infection and in vivo lipopolysaccharide-induced release of cytokines. An amplified mechanism of damage to the host. AB - Bacterial lipopolysaccharides (LPS) or endotoxins are potent triggers of the cytokine (CK) cascade. These CKs are immune mediators which produce many biological effects and could play a detrimental rather than beneficial role in the host. In this review emphasis will be placed on the participation of two CKs, tumor necrosis factor [TNF-alpha and interleukin (IL-1) beta], in the pathogenetic development of HIV infection. We have found that TNF and IL-1 circulate in exaggerated amounts in the blood of HIV-infected subjects from the earliest phases of infection. Furthermore, we have observed a strict correlation between plasma LPS and IL-1 beta levels, thus indicating that endotoxins could account for the production of CKs in the course of HIV infection. Finally, the demyelinating role of TNF-alpha either in experimental models or in the course of AIDS dementia complex is outlined. PMID- 1891986 TI - Immunopathogenesis of multiple sclerosis. AB - The immunopathogenesis of MS is discussed in the light of data recently obtained in Experimental Autoimmune Encephalomyelitis (EAE), a myelin specific experimental autoimmune disease reflecting the first, inflammatory phase of MS plaque generation. EAE is caused by CD4+ T cells specific for defined myelin protein, like MBP and PLP. In rats and mice there is a marked dominance of the autoantigenic peptide epitopes on the one hand, and the T cell receptor V regions on the other. During T cell mediated EAE, clonotypically counterregulatory CD8+ T cells are induced, which specifically neutralize the encephalitogenic T clones. PMID- 1891988 TI - Proceedings of the workshop on antigenic properties of myelin and the role of myelin in pathology. Naples, November 23, 1990. PMID- 1891987 TI - Are TNF-alpha and IL-1 beta relevant in the pathogenesis of migraine without aura? AB - Migraine without aura (MWA) is a clinical condition characterized by multiple immune deficits, which may play an important role in the pathogenesis of the disease. In this respect, previous studies have demonstrated that patients with MWA exhibit profound dysfunctions of phagocytosis and killing exerted by polymorphonuclear cells (PMN) and monocytes. This may correlate with the increased frequency of infectious processes observed in these patients. The overall results suggested to evaluate the presence of circulating cytokines (CKs) in subjects affected by MWA. In particular, the present data point out an exaggerated spontaneous release of tumor necrosis factor (TNF)-alpha in a group of MWA individuals, which correlates with detectable levels of bacterial lipopolysaccharides (LPS) in their plasma. In view of the different biological activities displayed by TNF-alpha in the host, such as effects on the nervous and vascular systems, hemodynamics modifications and demyelinating properties, the intervention of this CK in the pathogenesis of MWA will be discussed. PMID- 1891989 TI - Antigenic properties of myelin and the role of myelin in pathology. Introductory remarks. PMID- 1891990 TI - Appearance of white blood cells in the cerebrospinal fluid of rats following intravenous injection of lipopolysaccharide. AB - Intravenous injection of lipopolysaccharides (LPS), even in very low amounts (5 micrograms), leads to the appearance of white blood cells (WBC) in rat cerebrospinal fluid (CSF). The number of WBC is dependent on either dose of LPS or time of injection. The population of WBC consists of monocytes, granulocytes and lymphocytes, while red blood cells are not detectable. These findings support the pathogenetic role which LPS may play in the course of bacterial meningitis mostly in terms of pleocytosis and raised protein content in the CSF. PMID- 1891991 TI - [Immunohistochemical localization of proteoglycans in interstitial elements of human bladder cancer]. AB - The immunohistochemical localization of glycosaminoglycan side chains and core protein of proteoglycan was observed, using monoclonal antibodies, on 8 specimens of non-tumor bladder tissues and 26 specimens of bladder tumors obtained from total cystectomy or transurethral resection of bladder tumor (TUR-Bt). In non tumor tissues of human bladder examined, the surface of urothelial epithelium consisted of heparan sulfate as revealed with antibody HepSS-1, and submucosal interstitial elements consisted mainly of small proteoglycan having chondroitin 4 sulfate side chains as revealed with antibodies 6B6 and 9A2, respectively. On the other hand, in bladder tumors examined, the interstitial fibrous elements, the so called "specific stroma" in cancer cell nests, consisted mainly of large proteoglycans having chondroitin 4-sulfate or 6-sulfate side chains as revealed with antibodies 2B1, 9A2 and 3B3, respectively. Antibodies 2B1 and 3B3 are considered to be useful to demonstrate the involvement by invasive growth of bladder tumor cells. PMID- 1891992 TI - [Clinical evaluation of the bladder tumor marker "Tu-MARK-BTA"]. AB - Bladder tumor antigen (BTA) is a tumor marker isolated from the urine of individuals with TCC of the bladder. This antigen can be detected by the Tu-MARK BTA test, a simple and rapid slide latex agglutination test performed on freshly voided urine. Sensitivity and specificity of BTA were calculated, and the correlation with pathological grade, histological stage, and urinary findings were statistically evaluated (chi 2-test) in 110 patients (72 male, 38 female; age: 16-91, mean age 54.4) examined between September, 1989 and April, 1990 including 46 TCC of the bladder (primary 28, secondary 18; grade 1:10, grade 2:27, grade 3:9, pTis: 2, pTa: 2, pT1: 23, pT2: 5, pT3: 4, pT4: 2), and 64 benign diseases. Sensitivity was 45.6%, specificity was 60.9%. In bladder tumor cases a correlation was seen between BTA and stage (p less than 0.02), and between BTA and grade (P less than 0.05). The positive ratio was higher in T1-T4 (55.9%) than in Tis.Ta (p less than 0.02). A high positive ratio of BTA was seen in bladder tumor cases with hematuria (70%, p less than 0.01) and pyuria (86.7%, p less than 0.01). This method is easy and rapid and the values are highly correlated with stage. Therefore, it should be useful for not only screening but followup of bladder tumor. Furthermore, BTA in combination with urine cytology is a more useful way for diagnosing TCC of the bladder. PMID- 1891994 TI - [A case of retroperitoneal pleomorphic lipoma]. AB - A 71-year-old male patient was referred to our department for further examination for right retroperitoneal tumor. Exploration was done through a flank approach and the tumor with right adrenal gland was removed. A pleomorphic lipoma was diagnosed histopathologically. There have been 8 reported cases of pleomorphic lipoma including our present case in Japan and we discuss the pathogenesis and treatment of this rare disease. PMID- 1891993 TI - [A case of retroperitoneal ganglioneuroma]. AB - A 41-year-old female patient with a right retroperitoneal tumor for more than thirty years was referred to our department. Exploration was done through a transperitoneal approach and the tumor was removed. A ganglioneuroma was diagnosed histopathologically. There have been 99 reported cases with retroperitoneal ganglioneuroma including our present case in Japan and we discuss the pathogenesis and treatment of this rare disease. PMID- 1891995 TI - Spontaneous rupture of renal angiomyolipoma. AB - We report a case of renal angiomyolipoma with retroperitoneal hemorrhage treated by enucleation in a 47 year-old male. The mass in the anterior side of the left kidney, revealed by sonography and CT, was diagnosed as angiomyolipoma with a retroperitoneal hematoma caused by its spontaneous rupture. Removal of hematoma and enucleation of the tumor were performed after the diagnosis. Diagnosis and treatment of ruptured renal angiomyolipoma are discussed. PMID- 1891996 TI - [A case of infected solitary renal cyst treated with percutaneous puncture and drainage]. AB - A 29-year-old woman was admitted to our clinic with the chief complaint of high fever and right CVA tenderness. Treatment with antibiotics had not been completely effective in another hospital and she was referred to our hospital for further examination and treatment. Computed tomographic (CT) scan and ultrasonogram showed a right renal cyst. Therefore, we punctured and drained continuously the infected renal cyst for 16 days by a transcutaneous route. At her 3-month postoperative evaluation by CT scan, the cystic space vanished completely. We reviewed 43 cases of infected solitary renal cyst including our case in the Japanese literature and discussed the etiology and the treatment modality of infected renal cyst. PMID- 1891997 TI - [Pyeloureteritis cystica diagnosed by using a ureteroscope: a case report]. AB - We report a case diagnosed as pyeloureteritis cystica by ureteroscopic examination. A 70-year-old female was admitted to our hospital with microhematuria. Intravenous pyelography and retrograde pyelography demonstrated multiple filling defects in bilateral renal pelvis and ureters. Urinary cytology findings indicated class III on both side. Ureteroscope and cold cup biopsy were performed, and histological examination revealed chronic ureteritis. Forty-four Japanese cases including our case are herein reviewed. PMID- 1891998 TI - [Ureteral endometriosis: a case report]. AB - A 32-year-old female visited our clinic with the chief complaints of macroscopic hematuria and pollakisuria in February 18, 1987. Cystoscopic examination revealed findings of cystitis but bleeding from the ureteral orifice was not observed. IVP showed right non visualized kidney and retrograde pyelography demonstrated right ureteral stenosis on the lower ureter and right hydronephrosis. Total hysterectomy, right oophorectomy and right ureterolysis were carried out in March 5. Right lower ureter was buried in the fibrous tissue approximately over 2 cm above the crossing with iliac vessels. Dark reddish colored small tumor was noticed in the stenosed ureter and resected. The histological diagnosis confirmed endometriosis. A total of 37 cases of ureteral endometriosis in the Japanese literature was reviewed. PMID- 1891999 TI - [Carcinoma of the urinary bladder in a patient receiving cyclophosphamide for Wegener's granuloma: a case report]. AB - We present a case report of cyclophosphamide-induced bladder tumor. The patient is a 31-year old male who had received 240 g of cyclophosphamide for 8 years because of the therapy for Wegener's granuloma. Transurethral resection of bladder tumor was performed and transitional cell carcinoma pT1G2 ascertained by histological examination. Forty-three foreign cases and nine Japanese cases including our case are herein reviewed. PMID- 1892000 TI - [Retention cyst of the prostate with projection of hyperplastic tissue: report of a case]. AB - A 46-year-old man presented at Kasukabe City Hospital because of urinary retention. Digital rectal examination revealed soft distended mass in the retrovesical space. Transrectal ultrasonography and computed tomography showed a retrovesical cystic lesion of 14 x 11 x 10 cm in size and a mass protruding into the cyst from posterior lobe of the prostate. The cyst and the mass were removed suprapubically. The cyst was filled with 400 ml of clear yellowish fluid containing acid-phosphatase and prostate-specific antigen in a high concentration, but no spermatozoa. The mass protruded posteriorily from the prostate. The wall of the cyst was partly lined with double layer of columnar epithelium. The histological examination of the mass showed marked nodular hyperplasia and dilated acini of the prostate gland was seen around the cyst. A diagnosis of retention cyst of the prostate and nodular hyperplasia of the prostate were made. Cysts of the prostate are uncommon and retention cysts protruded by markedly hyperplastic prostatic tissue are extremely rare. PMID- 1892001 TI - [High-dose chemotherapy with autologous bone marrow transplantation as treatment for relapsing testicular cancer]. AB - In testicular cancer the tumor shows a high response rate to chemotherapy with dose responsiveness. However, when it is treated with high-dose chemotherapy, myelosuppression is severe. To overcome this problem, autologous bone marrow transplantation has been attempted. This is a report of an 18-year-old man with advanced nonseminomatous testicular cancer (stage IIB, embryonal carcinoma and teratoma) with relapse after first course of therapy. He was treated with high dose chemotherapy (etoposide 1,750 mg/m2, cisplatin 200 mg/m2, cyclophosphamide 60 mg/kg) and with autologous bone marrow transplantation. This patient has been in complete remission for more than 15 months without severe side effects or complications. We consider this a striking response to treatment in an early phase of relapsing testicular cancer. PMID- 1892002 TI - [Clinical study of RU 23908 (nilutamide) in prostatic cancer]. AB - To investigate the efficacy and the safety of RU23908 for the treatment of prostatic cancer, an early phase 2 study with the oral administration of 150 or 300 mg daily was performed in 47 patients with stage C or D prostatic cancer at 15 institutions from April 1987 to June 1988. Forty patients were evaluable for efficacy. Concerning the effect on the object lesion, the results of the overall evaluation revealed that complete or partial response (CR + PR) was obtained in 34 of the 40 cases (85.0%). As to the effect classified by site, CR + PR were observed in 35 out of the 40 cases with primary lesion (87.5%), in 10 of the 22 cases with bone metastasis (45.5%), in 5 of the 6 cases with lymph node metastasis (83.3%) and CR was observed in one case with lung metastasis. In the PAP evaluation, 33 out of the 34 cases were judged to be CR + PR (97.1%). The improvement rate of clinical symptoms was 88.9% for bone pain, 83.3% for dysuria and 45.5% for performance status. Adverse reactions were observed in 29 of the 47 cases (61.7%) investigated and 7 cases (14.9%) were withdrawn. During the study period of 12 weeks and the subsequent period of continued administration, 6 cases (12.8%) and 2 possible cases of interstitial pneumonia were diagnosed. From the above results, the treatment of prostatic cancer with RU23908 150 mg/day or 300 mg/day in combination with surgical castration showed an excellent clinical effect compared to conventional endocrine therapy, but has a problem of safety. Therefore, this drug may be expected to be a highly useful therapeutic drug, if safely is improved in the future by reviewing the dose. PMID- 1892003 TI - [Clinical evaluation of terodiline hydrochloride in patients with urinary frequency or incontinence]. AB - A clinical trial with the collaboration of 15 department of urology was performed to determine the usefulness of terodiline hydrochloride in 99 patients whose chief complaints were of pollakisuria or incontinence due to neurogenic bladder, psychogenic disease or chronic cystitis. The patients were orally given 24 mg once daily for 4 weeks. The final global improvement rate was 88.5% and the effective rates on subjective symptoms were; 66.2% for diurnal urinary frequency, 68.0% for nocturnal urinary frequency, 68.8% for urinary incontinence and 78.3% for nocturnal enuresis. Even for the cases having mild bladder outlet obstructive disease, the clinical effective rates were good. Mild side effects were observed in 10 patients, which were dry mouth and others. The results obtained from this trial suggest that terodiline hydrochloride may be useful for the treatment of urinary frequency and incontinence caused by detrusor instability. PMID- 1892004 TI - [Comparative study of cefpirome and ceftazidime in complicated urinary tract infections]. AB - We carried out a randomized multi-center study comparing cefpirome (CPR) 0.5 g b.i.d. (1 g group), 1.0 g b.i.d. (2 g group) and ceftazidime (CAZ) 1.0 g b.i.d. (CAZ group) in the treatment of complicated urinary tract infections. Patients who were over 16 years old and had underlying urinary tract disease, with bacteriuria of more than 10(4) cells ml or more and pyuria of more than 5 WBCs/hpf (x 400) or more were randomly allocated to receive either 0.5 g of CPR, 1.0 g of CPR or 1.0 g of CAZ twice a day for 5 days by intravenous drip infusion. The overall clinical efficacy of the treatment was evaluated by the criteria of the Japanese UTI Committee as excellent, moderate or poor, on the basis of the changes in pyuria and bacteriuria. A total of 530 patients were treated. Of these, 141 patients in the 1 g group, 136 in the 2 g group, and 140 in the CAZ group were evaluable for clinical efficacy. No significant differences in background characteristics were observed among the treatment groups. The overall clinical efficacy rate of the 1 g group, the 2 g group and the CAZ group was 80.1%, 76.5% and 71.4%, respectively. The differences were not statistically significant. The overall bacteriological eradication rate of the 1 g group, the 2 g group and the CAZ group was 81.0%, 88.1% and 83.8%. The differences were not statistically significant either. Against the enterococcus group, however, eradication rates were higher significantly in the 1 g and 2 g groups than in the CAZ group. The incidence of adverse reactions was 2.2% in the 1 g group, 0.6% in the 2 g group and 2.9% in the CAZ group. Abnormal laboratory data after medication were observed in 10.8% of the 1 g group, 12.1% of the 2 g group and 10.2% of the CAZ group, the difference not being statistically significant. There were no serious untoward reactions to medication. From the results obtained in this study, we consider that CPR is at least as useful as CAZ in the treatment of complicated urinary tract infections. PMID- 1892005 TI - [A study of relation between patterns of micturitional dysfunction and establishment of micturitional modality in stroke patients]. AB - We managed 246 patients with bladder dysfunction due to the first stroke in our hospital between January, 1983 and December, 1988. Of these 221 were in the chronic stage of stroke. A total of 213 patients were evaluated for types of bladder dysfunction by cystometry. We examined the relation between hemiplegic side and type of dysfunction or micturition activity, but obtained no significant relationship. Establishment of voluntary voiding pattern was considered to depend on the improvement of daily life activities. The catheter-free rate was 89.4%, while 10.6% of the patients, who could not receive sufficient nursing care or had severe medical problems, were obliged to keep an indwelling catheter. We conclude that establishment of a bladder retraining program is necessary not only medically but socially for improvement of quality of life in stroke patients. PMID- 1892006 TI - [Management of voiding dysfunction in geriatric general hospital: clinical experience of 315 cases with indwelling urethral catheter or diapers]. AB - In a geriatric general hospital, 157 patients with an indwelt urethral catheter and 158 patients using diapers were evaluated by detailed interview, urinalysis, measurement of residual urine, and cystometry during a period of 16 months from July, 1988, when the Department of Urology was established. As a result of therapeutic modalities, 94% of the patients were freed from the catheter or diapers. The indwelling catheter was found to be unnecessary in one-third of the patients. In addition, among the patients wearing diapers, one-third were capable of urinating only with the appropriate assistance of paramedical staff. It took less than 1 month for half but more than 1 year for 10% of the patients to be freed from the catheter or diapers. On the contrary, 19 patients could not be freed from the catheter or diapers, not due to bladder dysfunction but rather to mental, physical and social disabilities. These findings indicate that accurate diagnosis and management in collaboration with paramedical staff are required to solve urinating problems in the elderly. PMID- 1892007 TI - [Clinical studies on recurrent prostatic cancer]. AB - Between 1977 and 1989, we treated 114 new patients with prostatic cancer, and 99 of them responded to initial hormone-based treatment. Recurrence was seen in 28 of the 99 responders. The age at first admission ranged from 56 to 84 years, with a mean of 72.4 years. The mean interval between the start of follow-up and recurrence was 21.0 +/- 15.4 months (M +/- SE). The interval was 33.3 months for patients in stages B2 and C at initial treatment, 34.3 months for those in stage D1, and 15.6 months for those in stage D2. Stage D2 patients showed significantly earlier recurrence than the other patients (p less than 0.05). Patients with well, moderately, or poorly-differentiated adenocarcinoma at initial treatment developed recurrence after 62.5, 14.8, and 23.0 months, respectively, and there was no significant difference due to histological grade. As the mode of recurrence, the appearance of new lesions and the elevation of tumor marker levels were more frequently seen than local progression in patients with progressive disease at initial treatment. Pathological examination showed the tendency of recurrence for higher grade tumors. In comparison with those without recurrence, patients with recurrence had more advanced disease (p. 0.05). Only 11% of the patients showed partial response (PR) and 14.3% showed no change (NC) with multimodal therapy. The actual survival rates following initial treatment were 51.5% and 31.2% at 3 and 5 years, respectively, while those after recurrence were 49.3% and 12.5% at 1 and 3 years. PMID- 1892008 TI - [Flow cytometric analysis of DNA ploidy using paraffin-embedded germ cell tumors]. AB - The DNA content of paraffin-embedded materials was determined retrospectively using flow cytometry (FCM) in 36 germ cell tumors, and related to histological type, clinical staging and tumor marker. These histograms were classified from the basis of mode and variance into a diploid and an aneuploid pattern. We could evaluate the DNA histograms in 20 of 36 specimens (56%). Aneuploid patterns were found in 11 of 20 evaluated cases, but there was no correlation between ploidy patterns and histological types. Aneuploid patterns were demonstrated in 2 of 6 stage I cases (33%), and 4 of 5 stage II cases (80%) in seminomas. The difference between stage I and II cases was not statistically significant. There was no correlation between clinical staging and DNA content in non-seminomas. Of the seminomas with elevated human chorionic gonadotropin (HCG) titers, 3 of 4 cases showed aneuploid patterns. These findings indicate that the determination of DNA ploidy in seminomas may prove to be of prognostic value. PMID- 1892009 TI - [Microsurgical side-to-end epididymovasostomy: surgical technique and outcomes]. AB - The surgical procedures and results of microsurgical epididymovasostomy for obstructive azoospermia at the epididymis are reported. These procedures include the separation of a single epididymal tubule, an incision in the side wall, and a side-to-end anastomosis to the mucosa of the vas deferens under microscopic view. The tunica of the epididymis and the muscle layer of the vas are sutured together to support the mucosal anastomosis. Ten patients with epididymal obstruction underwent the side-to-end epididymovasostomy. The group consisted of two with Young's syndrome, one with an epididymal blow-out after vasectomy, one unsuccessful epididymoepididymostomy, 4 after epididymitis and 2 cases of unknown origin. After the operation, sperm appeared in 9 patients, and semen quality was normalized in 4 patients, all of whom impregnated their wives. Microsurgical side to-end epididymovasostomy is a much easier procedure than Silber's specific tubule method, and results in a high success rate. PMID- 1892010 TI - [Renal cell carcinoma in a horseshoe kidney]. AB - A 65-year-old man with pyuria visited our hospital. Physical examination had revealed a mass in the left upper quadrant of the abdomen. Intravenous pyelogram, ultrasonogram, computerized tomography and selective renal arteriogram suggested a hypervascular renal cell carcinoma on the left side of the horseshoe kidney. A left radical nephrectomy with division of the isthmus was performed. The pathological diagnosis indicated renal cell carcinoma consisting of clear cell type without invasion of the capsule or renal pelvis. Treatment with alpha interferon was started and has continued for six months with no evidence of recurrence. Only 35 cases of horseshoe kidney with a renal tumor have been reported in the Japanese literature. Among them, adenocarcinoma was present in 54.3% of the cases, renal pelvic tumor in 17.1%, and nephroblastoma in 14.3%. While adenocarcinoma in horseshoe kidney is seen less often than normal kidney, there is an increased incidence of both renal pelvic tumor and nephroblastoma. PMID- 1892011 TI - [Bilateral renal cell carcinoma in a patient receiving long-term dialysis]. AB - Bilateral renal cell carcinoma developing in a 55-year-old male receiving long term dialysis is reported. The patient, who had undergone maintenance hemodialysis for 12 years, was admitted in July, 1986 for the purpose of extensive examination of a right renal mass. CT scan and ultrasonography demonstrated an enlarged bilateral kidney associated with multiple cysts, containing a solid mass in the right upper pole. The patients underwent right nephrectomy under the diagnosis of right renal tumor. The solid tumor 4 x 3 cm in size revealed a grade 1 to 2 renal cell carcinoma pathologically. Two small tumors were recognized in other portions of the kidney. Multiple cysts of varying sizes, the largest 2 cm in diameter, replaced the renal parenchyma. The cyst walls frequently contained hyperplastic changes. The patient has been subsequently followed up for 2 years and 9 months and underwent left nephrectomy for suspected left renal tumor. The surface of the left kidney was covered by numerous cysts. The result of pathological examination was renal cell carcinoma, which was recognized in a total of 7 regions of the left kidney. The patient remains well on hemodialysis, with no evidence of recurrence or metastasis. PMID- 1892012 TI - [Benign hemorrhagic renal cyst: a case report]. AB - A case of benign hemorrhagic renal cyst in a 64-year-old man is reported. The patient was admitted to our hospital for further evaluation of left upper abdominal mass. CT scan and ultrasonic sonography showed a left giant renal cystic mass. The characteristic findings were thick and irregular wall and heterogeneous contents of the cystic mass. Selective renal arteriography showed a hypervascular area in a part of the cyst wall and hemorrhagic cyst was suspected by MR imaging. The presence of a malignant tumor in the cyst wall was suspected, and radical nephrectomy was performed. The specimen measured 18 x 12 x 8 cm and weighed 1,170 g. The cyst contained bloody fluid and a hemorrhagic degenerating mass. Pathohistological examination showed no evidence of malignant tumor at any site of the cyst wall. PMID- 1892013 TI - [Primary megaureter which showed aplasia of the muscle bundles on all dilated portions: a case report]. AB - A case of primary megaureter in a 59-year-old man which might shed light on the etiology and pathology is described. Intravenous urography and the computed tomography showed a left marked hydro-nephro-ureter which compressed the bladder and right ureter. In the left ureter, dilated portions stretched beyond dilated portions; that is, five non-dilated portions lay among four dilated portions. On histological examination of this specimen, all dilated portions showed aplasia of muscle in which muscle bundles were not observed, while all non-dilated portions including ureterovesical junction showed normal muscle layers. A case presentation and brief review of the literature were made. PMID- 1892014 TI - [A case of malignant melanoma of the penis]. AB - An 83-year-old male presented in October, 1988, with pigmented tumor lesions on the penis. The main tumor mass accompanied with necrotic bleeding, measuring 5 cm in diameter was located on the fore skin and glans penis. On the proximal shaft of the penis, there were three other black tumors, measuring from 0.5 to 3 cm in diameter. The distal urethra of the penis was clinically involved in the tumor mass and bilateral inguinal lymph nodes were palpable. Chest X-ray and liver scan both revealed multiple metastases. Tumor biopsy confirmed malignant melanoma. Phallectomy and bilateral inguinal lymph node biopsies were performed in October, 1988. Pathological findings revealed that a malignant melanoma had developed from the fore skin and glans penis, extended into the penile urethra and metastasized to bilateral inguinal lymph nodes. The patient gradually deteriorated in general condition and died of cancer 28 days later. The prognosis of malignant melanoma of the penis seems to be extremely poor. PMID- 1892016 TI - [Congenital perineal lipoma with accessory scrotum: a case report]. AB - A tumor mass covered with scrotum-like skin on its tip was found on the perineal region of 3-year-old boy since his birth. The mass was diagnosed as congenital lipoma, which was resected, because of its gradual enlargement. Histopathological findings of the tumor indicated perineal lipoma, and the scrotum-like portion was diagnosed as an accessory scrotum. In the Japanese literature, 7 congenital perineal lipomas (6 males, 1 female) have been reported and all male cases except 1 case (no description about scrotum) were accompanied with an accessory scrotum. We conclude that there may be a close relationship between congenital perineal lipoma and accessory scrotum. PMID- 1892015 TI - [Primary testicular carcinoid tumor with teratoma: a case report]. AB - We report a case of primary testicular carcinoid with teratoma and review the literature. A 68-year-old man was hospitalized with an asymptomatic left testicular mass. Left radical orchiectomy was performed under a diagnosis of testicular tumor. Histologically, the tumor showed a typical appearance of teratoma with carcinoid components. Barium studies, computed tomographic scan could not demonstrate any other tumor anywhere else. He is now being followed at our clinic without any evidence of recurrence. PMID- 1892017 TI - [Clinical application of EDAP LT-01 PLUS on extracorporeal shock wave lithotripsy for urolithiasis]. AB - With EDAP LT-01 PLUS, a new extracorporeal shock wave lithotriptor which generates shock waves by 320 ceramic elements activated by the piezoelectric effect and which was produced to be used for the treatments of both urolithiasis and gall bladder stones, we performed extracorporeal shock wave lithotripsy (ESWL) on 37 patients with urolithiasis between November 22, 1989 and July 31, 1990. Thirty seven target stones of 37 patients were located in the renal calyx (11 cases), renal pelvis (3 cases), UPJ (6 cases), renal calyx and pelvis (1 case), renal calyx and UPJ (1 case), renal calyx and upper ureter (1 case), upper ureter (9 cases), middle ureter (1 case), and lower ureter (4 cases). None of the patients needed anesthesia. The average number of treatments per case was 2.9 and the average total times of treatment per case was 196 minutes. The overall stone free rate one month after the last ESWL treatment was 54.1% (20/37), and no patients had any major side-effects. Judging from our present clinical application, we concluded that EDAP LT-01 PLUS is a useful extracorporeal shock wave lithotriptor for urolithiasis. PMID- 1892018 TI - Hysterosalpingography in the 1990s. AB - All physicians involved in the evaluation and treatment of infertility rely heavily on the information provided by hysterosalpingography. For many years this study has provided images of the lumina of the fallopian tubes that are not available by other diagnostic means, and it also gives the most accurate outline of the uterine cavity. Hysterosalpingography will therefore continue to be a valuable study in the upcoming decade, and it is important now to take account of the many advances in technology that impinge on the execution and interpretation of this study. In this article we first update the continuing debate about elements of the study itself, involving techniques and the choice of contrast material. We also consider surgical advances, such as the widespread use of microsurgical reconstruction of the fallopian tube, that increase the demand for hysterosalpingography. Since radiologists are asked to evaluate the results of surgery, it is essential for them to be familiar with the postoperative appearances of the fallopian tube. Finally, we consider what must be by far the most important development of the 1990s, the continuing integration of hysterosalpingography with new interventional and imaging techniques. Fallopian tube catheterization expands the examination of the fallopian tube and offers new therapeutic applications. Transvaginal sonography and MR imaging have allowed noninvasive exploration of the female pelvis. Correlation of hysterosalpingography and MR imaging is particularly useful in the diagnosis of uterine myomas and congenital uterine duplication anomalies when surgery to preserve or enhance the reproductive capacity of the uterus is indicated. Sonography and MR imaging should be correlated with hysterosalpingography to provide a more efficient diagnostic and therapeutic approach to the common mechanical causes of infertility. PMID- 1892019 TI - Chronic diffuse infiltrative lung disease: comparison of diagnostic accuracy of high-resolution and conventional CT. AB - We compared the accuracies of high-resolution CT (HRCT) and conventional CT in determining the specific diagnoses in 75 consecutive patients with chronic diffuse infiltrative lung disease. Without knowledge of clinical or pathologic data, two reviewers independently assessed three separate sets of CT scans in random order: three HRCT scans, three 10-mm collimation CT scans obtained at the same levels as the HRCT scans, and a complete conventional CT scan. The HRCT scans were obtained at the level of the aortic arch, tracheal carina, and 1 cm above the right hemidiaphragm by using 1.5-mm collimation and a high spatial resolution algorithm. Observers gave the most likely diagnosis along with their degree of diagnostic confidence. The correct diagnosis, irrespective of confidence level, was reached with 71% of the HRCT scans and with 72% of both the corresponding 10-mm and complete conventional CT scans. Confidence level 1 (definite) was reached with 49% of HRCT scans, 31% of corresponding 10-mm scans, and 43% of complete conventional CT examinations; the correct diagnosis was made in 92%, 96%, and 94% of those examinations, respectively. In none of the patients were findings on the limited HRCT scan normal when findings on the conventional CT scan were abnormal. We conclude that in most patients with chronic infiltrative lung disease a specific diagnosis can be made by obtaining a limited number of HRCT scans. PMID- 1892020 TI - Paraquat poisoning: findings on chest radiography and CT in 42 patients. AB - The purpose of this study is to describe the radiologic manifestations of paraquat-induced pulmonary damage, with special emphasis on the sequential changes seen with this condition. Paraquat is a herbicide that has toxic effects on the lungs, liver, and kidneys. Progressive respiratory failure is a frequent cause of death. We analyzed retrospectively 42 patients with a history of paraquat ingestion and abnormal findings on chest radiographs. Radiographic changes during the first week after ingestion included diffuse consolidation (26/39), pneumomediastinum with or without pneumothorax (15/39), and cardiomegaly with widening of the superior mediastinum (8/39). Small cystic and linear shadows began to appear at the end of the first week and were the preponderant parenchymal abnormality after 2-4 weeks. Focal honeycombing was the major parenchymal abnormality after 4 weeks. High-resolution CT of the lung 9 months after paraquat exposure revealed localized fibrosis containing small cysts. Our study shows that the pulmonary manifestations of paraquat poisoning begin with air-space consolidation, which then leads to end-stage lung. PMID- 1892021 TI - Diagnosis and localization of laceration of the thoracic duct: usefulness of lymphangiography and CT. AB - The usefulness of lymphangiography and CT in the diagnosis and localization of laceration of the thoracic duct was evaluated in 12 patients with chylothorax or chylous ascites after surgery. Bipedal lymphangiography was performed in all 12 patients. The last four patients studied also had CT after lymphangiography. Seven patients had abnormal findings on lymphangiograms; five with leaks from the thoracic duct, one with a lymphocele in a nephrectomy bed, and one with obstructed intestinal lymphatic vessels after thoracotomy. Five patients had no evidence of lymphatic leakage. CT in one patient with evidence of a leak on lymphangiography showed extravasation of contrast medium into the mediastinum and pleural space. CT in three patients with no abnormalities on lymphangiography also showed no abnormalities. Four of the five thoracic duct lacerations and the lymphocele were confirmed surgically. The diagnosis of obstructed intestinal lymphatic vessels was supported clinically. Four of the five patients with normal findings on lymphangiograms had resolution of their pleural effusions and no evidence of recurrence during a follow-up period of 1-27 months. One patient with normal findings on lymphangiography had an alternative diagnosis established at surgery. Laceration of the thoracic duct was accurately diagnosed and localized with lymphangiography, which allowed definitive surgical repair. CT was of little additional value in diagnosing these injuries. PMID- 1892022 TI - Normal anatomy of the thoracic inlet as seen on transaxial MR images. AB - The thoracic inlet can now be studied with high-resolution MR imaging. Recent advances in fold-over suppression (antialiasing software) allow for small fields of view without the usual problems of aliasing from the shoulders. This pictorial assay shows the normal anatomy that can be seen in this area on transaxial MR images. The vagus, phrenic, and recurrent laryngeal nerves can be seen as discrete entities. MR imaging can be used more often for pathologic conditions involving the lower portion of the neck and the thoracic inlet. PMID- 1892023 TI - Localization and needle aspiration of breast lesions: complications in 370 cases. AB - A prospective study of the immediate complications of 370 consecutive breast imaging procedures (203 wire localizations and 167 radiographically or sonographically guided fine-needle aspirations) is reported. Vasovagal reactions occurred in 27 (7%) of 370 cases, ranging in severity from syncope (four of 370, 1%) to mild light-headedness. These vasovagal reactions were independent of procedure type or use of local anesthesia, but were more common in younger patients. Other complications included prolonged (5 min or longer) bleeding (three of 370, 1%) and extreme pain (two of 370, 1%). One patient was found to have malignant hypertension. We conclude that wire localizations and imaging guided aspirations are generally well tolerated procedures. However, vasovagal reactions are frequent enough to warrant close observation of patients. Radiologists and breast-imaging personnel should be able to recognize and treat vasovagal reactions. PMID- 1892024 TI - Medicine in American art. Before and after. PMID- 1892025 TI - Value of dual-energy CT in differentiating focal fatty infiltration of the liver from low-density masses. AB - Focal (irregular, partial) fatty infiltration of the liver may simulate neoplastic or other hypodense masses on CT. On the basis of previous observations of the phenomenon that differences in X-ray attenuation diminish with increasing energy of X-rays used, we performed a preliminary study to determine if dual energy CT could be used to discriminate between fatty infiltration and hypodense liver masses. Dual-energy CT at 140 and 80 kVp was performed in 14 patients undergoing liver biopsy and in seven control subjects with presumedly normal liver. Attenuation measurements were taken, and the changes in attenuation between 140 and 80 kVp were calculated. The mean changes in attenuation were 3.5 H for normal liver (n = 7), 2.5 H for hypodense liver masses (n = 6), 13 H for fatty liver (n = 5), 0.3 H for fatty liver combined with hemochromatosis or hemosiderosis (n = 3), and 2 H for the spleen (n = 18). The change in attenuation increased as the fat content in the liver increased. Analysis of variance showed a statistically significant difference (p less than .001) between fatty liver and the other groups. A difference greater than 10 H was unique to fatty infiltration. These results suggest that dual-energy CT may help to differentiate focal fatty infiltration of the liver from low-density neoplastic or other lesions, but only if the iron content of the liver is not increased. PMID- 1892026 TI - Differentiation between hemangiomas and metastases of the liver with ultrafast MR imaging: preliminary results with T2 calculations. AB - We studied the efficacy of T2 measurements at high field strength in distinguishing between liver hemangiomas and hepatic metastases when an ultrafast (single-excitation) MR imaging technique is used. Fourteen patients with known liver tumors were imaged in a 2.0-T prototype ultrafast MR scanner with a spin echo (infinite TR and TE of 30-340 msec) pulse sequence. Each image was obtained with a total data acquisition time of 20 msec. T2 calculations for hepatic metastases (n = 6) showed a mean of 79.3 +/- 13.5 msec, whereas hemangiomas (n = 8) showed a T2 of 139.8 +/- 18.8 msec (p less than .0001). T2 values of lesions had a smaller relative standard deviation than previously reported, and the range of T2 values of hemangiomas (119-181 msec) and metastases (68-103 msec) did not overlap. Our preliminary results suggest that T2 calculations with ultrafast MR imaging may be useful for differentiating hemangiomas from metastases. We hypothesize that T2 values obtained from ultrafast MR images are more reliable than those obtained from conventional MR images, primarily because of the elimination of T1 information and effects of motion on image signal intensity. PMID- 1892027 TI - Detection of hepatic masses in patients with carcinoma: comparative sensitivities of sonography, CT, and MR imaging. AB - To evaluate the sensitivity of sonography, CT, and MR imaging in the detection of hepatic masses in carcinoma patients, we conducted a prospective study of 75 consecutive patients with gastrointestinal tumors who were admitted for surgical resection of the primary tumor. Sonography was performed with convex transducers of 3.5 and 5.0 MHz. Three noninvasive CT techniques were used: unenhanced CT scans, the incremental bolus dynamic scanning technique, and delayed scanning 4-6 hr after bolus injection of 60 g of iodine. MR images (1.5 T) were acquired as presaturated T1- and T2-weighted spin-echo sequences and as breath-holding fast low-angle shot (FLASH) 60 degrees and FLASH 15 degrees sequences. As it is difficult to distinguish benign from malignant masses solely on the basis of morphologic criteria, the techniques for each imaging method were designed to detect and not to characterize hepatic lesions. Each examination was interpreted blindly, and the results were compared with surgical findings, intraoperative sonography, and biopsy of the liver as the gold standard. All focal hepatic masses verified at surgery, malignant or benign, were included in the analysis. Sixty-five (68%) of 95 focal hepatic masses were detected by CT, 60 lesions (63%) by MR, and 50 lesions (53%) by sonography. Although lesions 1-2 cm were shown almost equally well by CT and MR (74% and 77%, respectively), the detection rate of smaller lesions (less than 1.0 cm) decreased more drastically with MR (31%) than with CT (49%). Sonography had a sensitivity of only 20% with the smaller lesions. All imaging techniques had a sensitivity of 100% for focal hepatic masses larger than 2.0 cm. Our results show that CT has a higher overall sensitivity (68%) than MR and sonography for the detection of focal hepatic masses. When the results of the three procedures are combined, the overall sensitivity is 77%. This is unsatisfactorily low, as CT and MR have a size threshold of about 1.0 cm and are relatively unreliable for the detection of smaller lesions. PMID- 1892028 TI - MR imaging in hydatid disease. AB - Hydatid cysts may develop anywhere in the body as a result of the presence of a viable parasite (Echinococcus granulosus). Depending on the condition of the parasite, the host reaction, and therapy, the hydatid cyst will degenerate and may eventually collapse, leaving an area of calcification in the host tissue. The purpose of this pictorial essay is to demonstrate the use of MR imaging in the diagnosis of the various stages of hydatid disease and in monitoring response to therapy. PMID- 1892029 TI - Gallstone lithotripsy: results when number of stones is excluded as a criterion for treatment. AB - The Siemens Lithostar Plus protocol (Siemens Medical Systems, Iselin, NJ) allows investigators to perform gallstone lithotripsy on patients regardless of the number of stones they have, provided the stones occupy less than 50% of the gallbladder lumen. The purpose of this study was to determine the interrelationships between stone burden, fragmentation response, and stone-free rates when treatment is not limited to three stones or fewer. Of 200 patients initially examined, 80 (40%) underwent lithotripsy. The mean number of treatments per patient was 2.1, and the mean number of shock waves per patient was 7386. In 60 patients in whom 6-month follow-up was available, the overall stone-free rate, based on actual results, was 32% (19/60). The stone-free rates for solitary stones, two or three stones, and four or more stones were 50%, 12%, and 26%, respectively. Regardless of number of stones, patients who ultimately became stone free had significantly smaller mean fragment size (0.25 cm) 2 weeks after lithotripsy than did those who did not become stone free (0.51 cm). Retrospective volume analysis showed that seven (47%) of 15 patients with multiple stones occupying less than 2000 mm3 were stone free; none became stone free when this volume was exceeded. Lithotripsy remains a practical option for patients with solitary stones. Comparable stone-free rates to those achieved for solitary stones can be obtained in patients with multiple stones, regardless of their number, provided treatment is aggressive and the stone aggregate is less than 2000 mm3. PMID- 1892030 TI - Gallbladder contractility: variation in normal subjects. AB - Gallbladder contractility can be quantified radiologically, but it is not known whether the degree of contraction exhibited by a person's gallbladder varies from day to day. Thirty healthy volunteers were studied with sonography on three separate occasions to determine the variation of individual gallbladder contractility. Using the ellipsoid method, we measured gallbladder volume after an overnight fast (fasting gallbladder volume) and between 45 and 60 min after a standard fatty meal (residual gallbladder volume). Percentage gallbladder contraction was calculated by dividing the difference between the fasting and residual gallbladder volumes by the fasting gallbladder volume and multiplying by 100. The 90 studies in 30 subjects exhibited a wide range of values: fasting gallbladder volume from 1.9 to 45.5 ml, residual gallbladder volume from 0.1 to 21.0 ml, and percentage gallbladder contraction from -10% to 99%. Within each subject, fasting gallbladder volume measurements varied from 1.5 to 26.2 ml (mean +/- two standard deviations, 10.3 +/- 5.1 ml) and residual gallbladder volume from 0.3 to 15.4 ml (5.1 +/- 3.8 ml). Percentage gallbladder contraction varied from 6% to 87% (28% +/- 18%). In 60% of the subjects, percentage gallbladder contraction values varied by more than 20%, and in 20% of the subjects it varied by more than 40%. These data show that a wide variation exists within a normal person in the degree of gallbladder contraction exhibited from one day to another, and a single test for gallbladder contraction can be misleading. PMID- 1892031 TI - CT appearance of splenic injuries managed nonoperatively. AB - This essay illustrates the appearance of the traumatized spleen on CT scans obtained during the course of conservative treatment. Although the CT appearance of acute rupture of the spleen has been adequately described, little has been reported about the appearance of the spleen as it heals after trauma. Examples of CT studies of splenic injuries illustrate the various changes in appearance over time in the traumatized spleen that is treated nonoperatively. PMID- 1892033 TI - Systemic Yersinia enterocolitica infection associated with iron overload and deferoxamine therapy. PMID- 1892032 TI - The value of barium as a gastrointestinal contrast agent in MR imaging: a comparison study in normal volunteers. AB - Preliminary data suggest that barium sulfate suspension is a potentially useful negative gastrointestinal contrast agent for MR imaging. To evaluate this hypothesis in a controlled fashion, abdominal and pelvic MR studies of 10 normal volunteers were performed before and after both oral (600-900 ml) and rectal (400 ml) administration of barium. Standard spin-echo coronal T1-, axial T1-, proton density-, and T2-weighted images were obtained at 1.5 T. Images obtained were randomized and interpreted by three observers, who evaluated bowel visualization and delineation of normal anatomy. Bowel segments evaluated were stomach, duodenum, proximal small bowel, proximal colon, distal colon, and rectum. Anatomic structures examined were pancreatic head, pancreatic body, pancreatic tail, retroperitoneum, spleen, liver, pelvic side walls, uterus, vagina, bladder, prostate, and seminal vesicles. Data concerning barium tolerance and safety were recorded. Descriptive, percent change, and kappa statistics were analyzed. Pairwise agreement techniques and repeated measures analysis of variance were performed. This statistical assessment showed a significant improvement in both bowel visualization (59-123% improvement, depending on the segment) and delineation of normal anatomy (23-68% improvement, depending on the structure) after barium administration, particularly on T1-weighted images. In addition, barium was a well-tolerated and safe contrast agent that did not produce artifacts. Our results show that barium sulfate is a useful negative gastrointestinal contrast agent for MR because it improves bowel visualization and delineation of abdominal anatomy, particularly on T1-weighted sequences. PMID- 1892034 TI - Percutaneous biopsy of left adrenal masses: prevalence of pancreatitis after anterior approach. AB - Acute pancreatitis is an unusual but recognized complication of percutaneous aspiration biopsy of the pancreas. As the pancreatic tail is located anterior to the left adrenal gland, percutaneous biopsy of a left adrenal mass via the anterior approach may result in needle passage through the tail of the pancreas with subsequent potential development of pancreatitis. To evaluate this risk, we retrospectively reviewed 48 CT-directed percutaneous aspiration biopsies of left adrenal masses done between 1984 and 1989 at two institutions. Positioning of the patient, the course of the needle, the number of needle passes, and the size of the needle were analyzed. Thirty-three (69%) of 48 biopsies of a left adrenal mass were performed by using the anterior approach. The pancreas was traversed by one or more needles in 32 of 33 cases. Biopsies were performed with 20- to 22 gauge needles, and the number of needle passes varied widely. The medical records of the 33 patients in whom the anterior approach was used also were reviewed for complications. Acute pancreatitis, which required 11-13 days of hospitalization, developed in two patients (6%). None of the other 31 patients suffered a complication. We conclude that the pancreatic tail is routinely traversed by the biopsy needle when biopsy of a left adrenal mass is done via the anterior approach and that severe acute pancreatitis can occur as a result. PMID- 1892035 TI - Castleman disease of the adrenal gland: MR imaging features. PMID- 1892036 TI - Cystic carcinoma of the prostate: findings on transrectal sonography. PMID- 1892037 TI - Diagnosis of gestational trophoblastic disease: value of endovaginal color flow Doppler sonography. PMID- 1892038 TI - Radiation-induced osteochondroma. PMID- 1892039 TI - Sonography of the normal elbow. AB - Sonography was performed in 30 normal patients, neonatal to 45 years old, to illustrate our technique for complete and rapid examination of the elbow joint. Sonography is an easy, noninvasive method of evaluating the articulating surfaces, tendinous insertions, and supporting soft tissues of the elbow joint. Reliable identification of both normal and diseased anatomy is possible at all ages. Familiarization with the sonographic appearance of the six elbow ossification centers aids in sonographic interpretation. PMID- 1892040 TI - Osteoarthritis of the knee: comparison of radiography, CT, and MR imaging to assess extent and severity. AB - Although conventional radiography is the method most frequently used for monitoring progression of osteoarthritis, it may not show osteoarthritic changes of the knee until late in the disease, and it may show involvement of only one or two compartments in patients who have tricompartmental disease. We compared radiography, CT, and MR imaging for assessing the extent and severity of osteoarthritis of the knee in 20 patients. Radiography included posteroanterior weight-bearing, true lateral, and sunrise patellar projections. Axial CT scans were reformatted in sagittal and coronal planes. MR imaging consisted of spin echo (600-800/20; 2000/60, 120 [TR/TE]), and gradient-echo (600/30, theta = 30 degrees) sequences. The severity of osteoarthritic changes was graded from 0 to 3. MR frequently showed tricompartmental cartilage loss when radiography and CT showed only bicompartmental involvement in the medial and patellofemoral compartments. In the lateral compartment, MR showed a higher prevalence of cartilage loss (60%) than radiography (35%) and CT (25%) did. In the medial compartment, CT and MR showed osteophytes in 100% of the knees, whereas radiography showed osteophytes in only 60%. Notably, radiography often failed to show osteophytes in the posterior medial femoral condyle. On MR images, meniscal degeneration or tears were found in all 20 knees studied. Partial and complete tears of the anterior cruciate ligament were found in three and seven patients, respectively. MR is more sensitive than radiography and CT for assessing the extent and severity of osteoarthritic changes and frequently shows tricompartmental disease in patients in whom radiography and CT show only bicompartmental involvement. MR imaging is unique for evaluating meniscal and ligamentous disease related to osteoarthritis. PMID- 1892041 TI - Diagnosis of osteomyelitis in the presence of soft-tissue infection and radiologic evidence of osseous abnormalities: value of leukocyte scintigraphy. AB - To evaluate the usefulness of 111In-leukocyte scintigraphy for identifying osteomyelitis in the presence of soft-tissue infection, we prospectively studied 45 bone sites adjacent to soft-tissue infection in patients with abnormal findings on radiographs and 99mTc bone scans that were suggestive of osteomyelitis. 111In-leukocyte scans were analyzed in terms of the intensity of abnormal uptake and its location relative to bone. The diagnosis of osteomyelitis was established from results of percutaneous bone biopsy culture (n = 35), histologic examination of surgical specimens (n = 8), and clinical follow-up (n = 2). Osteomyelitis was present at 22 sites, including 16 of 18 sites with increased leukocyte uptake in bone, resulting in a sensitivity of 73%, specificity of 91%, and positive predictive value of 89% for this finding. Osteomyelitis was present at four of 17 sites with predominantly soft-tissue localization of leukocyte activity in the region of bone, none of seven sites with normal leukocyte scans, and two of three sites with diminished leukocyte uptake in bone. Although not helpful in distinguishing infectious from noninfectious bone abnormalities, 3- and especially 24-hr bone scans viewed in conjunction with leukocyte studies provided important correlation to aid in estimating the location of focal abnormal leukocyte uptake. The finding of soft tissue infection with increased uptake of labeled leukocytes that extends to involve adjacent bone strongly suggests concurrent osteomyelitis. When the presence of abnormal leukocyte uptake in bone is uncertain, additional imaging and possibly biopsy may be required to establish or exclude the diagnosis of osteomyelitis. PMID- 1892042 TI - Abnormalities of the foot in patients with diabetes mellitus: findings on MR imaging. AB - The MR appearances of foot problems in patients with diabetes mellitus are illustrated. MR has been found to be effective in the diagnosis of osteomyelitis, the most common indication for imaging the feet of diabetic patients. MR has the ability to image numerous pathologic processes, especially subtle soft-tissue changes, that are not detectable with other imaging methods. PMID- 1892043 TI - Septic arthritis of the hip: a complication of a rectal tear associated with pelvic fractures. PMID- 1892044 TI - Response of osteosarcoma and Ewing sarcoma to chemotherapy: imaging evaluation. AB - The importance of diagnostic imaging in evaluating therapeutic response of bone sarcomas has increased with the use of chemotherapy administered before radiation therapy or surgery. The information provided by imaging studies is used to estimate prognosis; modify preoperative chemotherapy; and plan radiation therapy, surgery, and postoperative chemotherapy. This review examines the value and illustrates some pitfalls of traditional imaging methods, including conventional radiography, angiography, CT, and radionuclide scintigraphy, and discusses recent efforts to monitor therapy by using MR imaging and MR spectroscopy. PMID- 1892046 TI - Percutaneous retrieval of an embolized arterial sheath. PMID- 1892045 TI - Distal aortopulmonary window with aortic origin of the right pulmonary artery and interruption of the aortic arch (Berry syndrome): diagnosis by MR imaging. PMID- 1892047 TI - Society of Thoracic Radiology ninth annual meeting and postgraduate course, May 1991. PMID- 1892048 TI - Optical character recognition for storing literature references. PMID- 1892049 TI - Anaphylactic reactions to latex balloons. PMID- 1892050 TI - Retained E-Z-EM balloon barium enema tip. PMID- 1892052 TI - High serum level of alkaline phosphatase is not a contraindication for embolization of the hepatic artery in liver cancer. PMID- 1892051 TI - Hepatic sarcoidosis as a cause of hypertrophy of the caudate lobe: sonographic findings. PMID- 1892053 TI - MR and CT diagnosis of intracranial lipoma. PMID- 1892054 TI - Unusual spread of sinonasal carcinoma via the eustachian tube into the middle and external ear. PMID- 1892055 TI - A symposium: thrombosis and thrombolysis in unstable angina. Introduction. PMID- 1892056 TI - A symposium: thrombosis and thrombolysis in unstable angina. October 4-5, 1990, Como, Italy. Proceedings. PMID- 1892058 TI - Thrombolysis in refractory unstable angina. AB - Multiple drug therapy, including nitrates, beta blockers, calcium antagonists, aspirin, and heparin, has been advocated as effective in the treatment of unstable angina, a syndrome with a multifactorial pathogenesis. Recently, plaque rupture and thrombosis have been demonstrated as the most important pathogenetic mechanisms. Nevertheless, clear-cut results on the effects of thrombolytic treatment in unstable angina are still lacking. Some possible explanations why the medical treatment of unstable angina has still not yet been standardized, whereas that of myocardial infarction has, are suggested. A review of randomized and nonrandomized studies published on this topic evaluating the role of different thrombolytic agents in unstable angina is presented. In addition the role of coronary angiography is discussed. In view of the disappointing results of coronary artery bypass surgery performed in the acute phase of the disease, one of the goals of clinical research is to identify subsets of patients at high and low risk and who undergo different types of therapeutic interventions. To support published data suggesting that total myocardial ischemia has a significant impact on prognosis, we present our results of a study carried out on patients with refractory unstable angina treated with thrombolytic therapy and evaluated with continuous electrocardiographic monitoring in the attempt to correlate total myocardial ischemia with short-term prognosis. Data in favor of the prognostic role of continuous electrocardiographic monitoring in unstable angina are also reviewed. Finally, we propose some suggestions that might be useful for future studies. PMID- 1892057 TI - Mechanisms of platelet activation: thromboxane A2 as an amplifying signal for other agonists. AB - Thromboxane (Tx) A2 is a product of cyclooxygenase catalyzed metabolism of arachidonic acid. It is formed via prostaglandin (PG) endoperoxide intermediates (PGG2 and PGH2) by a specific synthase. PGH2 appears to exert the same biologic effects as TxA2. The cDNA for a TxA2 receptor has been cloned from a human placental library. Although pharmacologic and biochemical studies suggest the presence of multiple isoforms, this remains to be confirmed at the molecular level. A hydropathy plot of the deduced amino acid sequence of the available clone suggests that it has 7 transmembrane spanning domains, typical of a G protein linked receptor. Pharmacologic studies imply that Tx receptors in platelets are linked to phospholipase C activation via pertussis toxin insensitive G proteins. Candidates include the 42 kD Gq and the 60 kD Ge. TxA2 acts as an amplifying signal for platelet agonists and the response to this eicosanoid is tightly regulated. Mechanisms include rapid hydrolysis of the agonist to the inactive TxB2, autoinactivation of Tx synthase, rapid homologous TxA2 receptor desensitization due to receptor-G protein uncoupling, coincidental sensitization to counterregulatory Gs linked receptor systems and stimulation of prostacyclin formation by TxA2. Due to its role as an amplification signal in platelet activation, inhibition of Tx synthesis and action is an effective mechanism for preventing platelet-dependent vascular occlusion. Aspirin is of proven efficacy in this regard. Tx synthase inhibitors and antagonists are under clinical investigation. PMID- 1892059 TI - Thrombolysis in postinfarction angina. AB - Postinfarction angina carries a poor prognosis, with a 20-70% incidence of recurrent myocardial infarction (MI) or death within the subsequent 3-6 months. The pathophysiologic mechanisms causing postinfarction angina may include thrombus, complex coronary arterial lesions that form a nidus for thrombus formation, inadequate collateral supply following acute MI, or intimal endothelial dysfunction. The role of thrombus has been established in the pathophysiology of Q-wave MI, and thrombolytic treatment of patients presenting with acute transmural MI has been shown to salvage left ventricular function and to reduce mortality. However, thrombolytic therapy for the acute MI does not reduce the incidence of recurrent ischemia or infarction, as is evident from the 18-26% incidence of recurrent ischemia reported in the Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) and Thrombolysis in Myocardial Infarction (TIMI) trials. In the Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico (GISSI) study the incidence of reinfarction was documented as 4% in the streptokinase group, which was actually significantly greater than in the placebo group (2%). In a randomized placebo controlled study of thrombolysis for postinfarction angina, 29 patients were randomized to placebo (P group, n = 17) or to thrombolytic therapy (T group, n = 12). Patient groups were similar with respect to age, location of MI, ejection fraction, severity of coronary artery disease, and antianginal therapy. Patients underwent coronary angiography 6 +/- 1 days postinfarction. Filling defects consistent with intracoronary thrombus was seen in 11 of 12 T group patients and in 11 of 17 P group patients prior to treatment. Lysis occurred in 7 of 11 T patients and 1 of 11 P (p less than 0.02). Holter-detected silent ischemia was compared pre- and posttherapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1892060 TI - Percutaneous transluminal coronary angioplasty for unstable angina. AB - Coronary angioplasty is an effective treatment for patients with angina at rest, either refractory or initially stabilized but returning despite pharmacologic treatment, and with early postinfarction angina. The procedure has a high initial success rate, but there is an increased risk of major complications resulting from a higher incidence of acute closure, which may be related to preexisting thrombus. Resolution of this problem may be achieved by the use of more potent antiplatelet treatment, pretreatment with thrombolytic agents, or treatment that can be applied locally (e.g., laser energy, atherectomy) at the site of the unstable plaque. Results in this study have been obtained from selected groups of patients: those with predominantly single-vessel disease and well-preserved left ventricular function. It remains to be determined whether the same benefits can be achieved in patients with multivessel disease or in those who have severely reduced left ventricular function. PMID- 1892061 TI - Integration of anticoagulation, thrombolysis and coronary angioplasty for unstable angina pectoris. AB - Unstable angina pectoris remains a challenging acute ischemic syndrome to treat despite recent randomized trials that confirm the benefit of intravenous heparin. Coronary angioplasty, which is often required to treat the underlying arterial lesion, is adversely affected by the presence of thrombus with at least a 2-fold increase in abrupt closure. Four studies with heparin treatment prior to angioplasty indicate a reduction of abrupt vessel closure from 8-33% to 0-6% with apparent reduction of morbidity; no controlled trials are thus far available for heparin pretreatment. Another therapeutic alternative, thrombolytic therapy, has had quite equivocal results with several negative small studies. When angioplasty has been performed with thrombolytic therapy, a nonfibrin-specific plasminogen activator appears to be preferable. Newer studies that focus on thrombin inhibitors that bind to clot-bound thrombin and potent antiplatelet agents are in the early phase of clinical investigation. This review offers current recommendations for the integration of heparin, thrombolysis, and coronary angioplasty for unstable angina pectoris. PMID- 1892062 TI - The elusive cause of instability in unstable angina. AB - The causes of unstable angina are still largely unknown. However, some facts deriving from angiographic, postmortem, and pathophysiologic studies are well established. Angiographic findings: coronary thrombi and complicated stenoses are more frequent in unstable than in stable angina. Conversely, the severity of coronary atherosclerosis and the development of collateral circulation is similar in both coronary syndromes. Postmortem findings: the following features are more frequent in unstable than in stable angina: (1) mural thrombi, which often represent out-growth from the inside of a fissured plaque; (2) inflammatory cells at the site of plaques and in perivascular nerves; and (3) contraction bands in smooth muscle cells of the media surrounding plaques. However, fissured plaques can be found in 10% of individuals dying of noncardiac causes, and fissured plaque may occasionally be missing under the coronary thrombus in unstable angina. Pathophysiologic findings: patients with unstable angina compared with those with stable angina exhibit: (1) higher levels of serotonin in the coronary sinus; (2) higher systemic levels of fibrino-peptide A; (3) higher urinary levels of thromboxane A2 metabolites; and (4) a greater coronary reactivity to constrictor stimuli. A critical analysis of these established facts is required to set the stage for a better comprehension of the causes which can cause a coronary segment to progress in a stuttering way toward acute persistent coronary occlusion and myocardial infarction. Plaque fissure is likely to be an important background thrombogenic stimulus in many cases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1892063 TI - Pathogenesis of thrombosis in unstable angina. AB - Plaque rupture of the thinned, weak fibrous cap infiltrated by macrophages and overlying a pool of lipid in the arterial wall initiates the acute thrombotic event of unstable angina. Thrombosis may be advanced within minutes. Most lesions that precede plaque rupture are minor (less than 50% stenosis); thus, thrombus greatly contributes to sudden flow limitation and onset of symptoms. If thrombosis can be totally blocked (not possible with current antithrombotic agents), clinical events should be preventable, and endogenous thrombolysis may be possible within days. Local and systemic factors contribute to arterial thrombosis. With type III injury (fissure into plaque or media) platelet-rich thrombus anchors in the fissure, tracks along the site of deep injury, extends into the lumen, and requires the highest blood level of specific thrombin inhibition (a molar concentration that inhibits the total concentration of prothrombin in circulating blood). Thus, the thrombin content requiring inhibition in type III injury is highest. Local factors for thrombosis associated with type III injury include the rheology of blood flow (increased shear rate forces platelets to the periphery) and substrates in the arterial wall. Plaque substrates include the more thrombogenic collagens (types I and III and diabetic or glycosylated collagen), tissue thromboplastin, lipid gruel, thrombin bound to arterial wall matrix, and decreased prostacyclin. There is a direct relation between platelet deposition (thrombus) and local vasoconstriction, which may perpetuate each other. Thrombus as a substrate is more thrombogenic than type III arterial injury.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1892064 TI - The heart in fatal unstable angina pectoris. AB - Compared to patients with sudden coronary death and acute myocardial infarction, relatively little morphologic data has been reported in patients with unstable angina pectoris. This article reviews necropsy data collected from one laboratory on unstable angina pectoris. From these data, several observations are appropriate: (1) Patients with unstable angina as a group have more coronary narrowing by atherosclerotic plaque than do patients with sudden coronary death or acute or healed myocardial infarction. (2) Patients with unstable angina have a much higher frequency of severe narrowing of the left main coronary artery than do patients in other coronary subsets. (3) The coronary atherosclerotic plaques in unstable angina consist primarily of fibrous tissue, and they are more similar to those found in patients with sudden coronary death than in patients with acute myocardial infarction. (4) The frequency of acute coronary lesions (thrombi, plaque rupture, and plaque hemorrhage) is similar to that observed in patients with sudden coronary death and significantly less than that observed in acute myocardial infarction. (5) The frequency of multiluminal channels throughout the major coronary arteries is significantly higher in unstable angina compared to sudden coronary death or acute myocardial infarction. (6) The major epicardial arteries and the heart are smaller in patients with unstable angina than in patients with sudden coronary death or acute myocardial infarction. (7) The left ventricular cavity is usually of normal size in patients with unstable angina and therefore left ventricular function is usually normal. PMID- 1892065 TI - Coronary thrombosis: pathogenesis and clinical manifestations. AB - The majority (greater than 75%) of major coronary thrombi are precipitated by a sudden rupture of the surface of an atherosclerotic plaque (plaque fissuring) causing platelet aggregation where thrombogenic subendothelial tissue has been exposed. Whether the thrombus remains mural and limited, just sealing the rupture, or evolves into an occlusive thrombus seems to depend on: (1) the amount and character of exposed thrombogenic material; (2) the actual thrombotic thrombolytic equilibrium; and (3) local flow disturbances due to preexisting atherosclerotic stenosis. Thrombus formation may take place within the stenosis, where blood velocity and shear forces are highest, or it may take place or extend poststenotically, where flow separation, recirculation, and turbulence prevail. Platelet aggregation within the stenosis is responsible for the primary flow obstruction, but fibrin subsequently enmeshes the platelets and thus stabilizes the thrombus. Most thrombi have a layered structure, indicating an episodic growth that may alternate with thrombus fragmentation and peripheral embolization: thrombosis and thrombolysis are dynamic processes occurring simultaneously. If the platelet-rich thrombus at the rupture site evolves into an occlusive thrombus, the blood proximal and distal to the occlusion may stagnate and coagulate, giving rise to a secondarily formed red stagnation thrombosis consisting predominantly of erythrocytes held together by fibrin membranes. A ruptured plaque with a dynamic thrombosis superimposed (with or without spasm) seems to underlie the great majority of acute ischemic syndromes: unstable angina, acute infarction, and sudden death. The clinical presentation and the outcome depend on the severity and duration of ischemia: whether the obstruction is occlusive or nonocclusive, transient or persistent--modified by the magnitude of collateral flow. PMID- 1892066 TI - Coronary atherosclerotic plaques with and without thrombus in ischemic heart syndromes: a morphologic, immunohistochemical, and biochemical study. AB - We investigated incidence, severity, and distribution of coronary atherosclerosis, acute thrombosis, and plaque fissuring in ischemic heart disease (both unstable-acute syndromes and chronic ischemia) and in nonischemic controls. We also studied the structural, immunohistochemical, and biochemical profile of plaques, with and without thrombus, including morphometry, immunophenotyping of inflammatory infiltrates, cytokine presence, and ultrastructural features. Critical coronary stenosis was almost the rule in both acute and chronic ischemic series (greater than 90%) whereas it reached 50% in control subjects. Thrombosis was principally characteristic of unstable-acute ischemic syndromes (unstable angina, 32%; acute myocardial infarction, 52%; cardiac sudden death, 26%) but was also found in chronic ischemia (stable angina, 12%; ischemic cardiomyopathy, 14%) and in control subjects (4%). Plaque fissuring without thrombus occurred in low percentages in lipid-rich, severe eccentric plaques in most series. Major differences were found between pultaceous-rich versus fibrous plaques rather than between plaques with or without thrombus. Pultaceous-rich plaques were frequent in sites of critical stenosis, thrombosis, and ulceration. Inflammatory infiltrates, i.e., T cells, macrophages, and a few beta cells, mostly occurred in lipid-rich, plaques unrelated to thrombus. In adventitia, infiltrates were a common finding unrelated to any syndrome. Necrotizing cytokines such as alpha-TNF were immunohistochemically detected in macrophages, smooth muscle, and intimal cells and detected by immunoblotting in 67% of pultaceous-rich plaques, either with or without thrombus. Immune response mediators such as IL-2 were also expressed in analogous plaques but in a minor percentage (50%-40%). Media were extensively damaged in severely diseased vessels with and without thrombus. Ultrastructural study showed that the fibrous cap was either highly cellular or densely fibrillar. Intimal injury with collagen exposure was often associated with platelet adhesion, whereas foamy cell exposure was not. In conclusion, investigated parameters were essentially similar in plaques, both with and without thrombus, whereas major differences were found between pultaceous-rich and fibrous plaques. Since platelets adhere to exposed collagen and not to foam cells, the type of exposed substrates could play a major role in thrombosis. PMID- 1892067 TI - Platelet activation in the pathogenesis of unstable angina: importance in determining the response to plasminogen activators. AB - Unstable angina is a clinical syndrome of recurrent myocardial ischemia. In some cases, this reflects episodic platelet activation and coronary thrombosis. Thus, the biosynthesis of thromboxane A2, which is largely derived from activated platelets, is increased, often coincident with chest pain. The major role of platelets in unstable angina may influence the response to plasminogen activators. Platelets increase the resistance of thrombi to lysis, by inducing clot retraction and cross-linking and by releasing inhibitors. Thus, coronary thrombi in unstable angina may be resistant to lysis. Furthermore, both t-PA and streptokinase cause platelet activation and thrombin formation in vivo, possibly via plasmin. Plasmin can activate platelets and factor V directly. These prothrombotic effects of plasminogen activators may limit their activity in unstable angina. At the very least, their therapeutic efficacy may be highly dependent on the coadministration of potent antiplatelet agents and anticoagulants. PMID- 1892068 TI - Fibrinopeptide A excretion in urine: a marker of the cumulative thrombin activity in stable versus unstable angina patients. AB - Plasma levels and 24-hour urine excretion of fibrinopeptide A were measured in a consecutive series of 179 patients with angina pectoris. Sixty-four patients had stable angina and 115 patients had unstable angina. Urine was collected over 24 hours the day before coronary arteriography, and blood samples were taken at the end of urine collection. When the values of fibrinopeptide A in plasma and in the 24-hour urine specimens were compared, no significant correlation was found in patients with either stable (rs = 0.16, difference not significant) and unstable (rs = 0.07, difference not significant) angina. The concentrations of fibrinopeptide A in the plasma did not differ significantly when patients with stable angina (range 0.1 to 82.6, median 7.4 ng/mL) were compared with patients with unstable angina (range 0.2 to 61.7, median 14 ng/mL, p = 0.055), whereas fibrinopeptide A 24-hour urinary excretion was significantly higher in patients with unstable angina (range 0.3 to 38.1, median 11.8 micrograms/24 hr) than in patients with stable angina (range 0.4 to 38.1, median 3.8 micrograms/24 hr, p less than 0.001). Twenty-four-hour urine excretion of fibrinopeptide A in patients with unstable angina and angiographically documented intracoronary thrombi were higher than the corresponding values in patients with unstable angina without such angiographic characteristic (p less than 0.001). The largest increase in plasma and urine concentration of fibrinopeptide A was observed in patients whose first episode of angina at rest occurred within the previous 48 hours. We conclude that the cumulative thrombin activity, assessed by 24-hour urinary excretion of fibrinopeptide A, is a more useful index, compared with single fibrinopeptide A measurement in plasma, for discriminating between patients with stable and with unstable angina pectoris. PMID- 1892069 TI - Granulocyte function in coronary artery disease. AB - Granulocytes defend the body against invading microbes by producing a complex armamentarium of toxic substances, such as proteolytic enzymes, oxygen radicals and arachidonic acid metabolites. Under certain circumstances, however, such compounds may be released in the absence of phagocytosable particles, resulting in injury to normal cell and connective tissue degradation. Recent experimental studies have emphasized the potential role of granulocytes in the pathogenesis of myocardial ischemia. Clinical investigations have also shown alterations in neutrophil function in stable and unstable clinical manifestations of ischemic heart disease. "Priming" of granulocytes in stable forms of coronary disease may predispose to the subsequent development of acute coronary events, whereas activation of neutrophils may lead to alterations in vascular permeability and coronary flow regulation, leading to further myocardial and endothelial injury in acute myocardial infarction, unstable angina and coronary angioplasty. PMID- 1892070 TI - Intimal disruption and coronary thrombosis: its role in the pathogenesis of human coronary disease. PMID- 1892071 TI - Angiography in unstable angina. AB - Within the last decade, it has been appreciated that the acute coronary syndromes of unstable angina, non-Q-wave, and Q-wave myocardial infarction often share a common pathogenesis based on plaque disruption and thrombosis. Such "acute" lesions frequently have a characteristic angiographic appearance with sharp overhanging edges, irregular borders, and intraluminal lucency. This review focuses on the benefits and limitations of qualitative assessment of coronary lesion morphology, with respect to the sensitivity, specificity, and prognostic significance of complex lesions and intracoronary thrombi. Angiographic findings following thrombolysis for unstable angina are discussed, as well as the possible role for thrombolytic therapy as an adjunct to angioplasty in unstable angina. PMID- 1892072 TI - Characterization of atherosclerotic lesions by intravascular ultrasound: possible role in unstable coronary syndromes and in interventional therapeutic procedures. PMID- 1892073 TI - Antiplatelet and antithrombotic therapy in unstable angina. AB - In 4 well-controlled clinical trials, aspirin reduced the incidence of coronary events in unstable angina. The benefits were present during the acute, subacute and more chronic phases of the disease and were independent of the doses and of other protocol differences. This benefit of aspirin can be extended to some, but not all, other antiplatelet drugs. In 4 clinical trials, heparin used acutely added substantial benefit to the management of unstable angina, reducing the event rate and also the incidence of refractory angina more than aspirin. The long-term benefit of antithrombin therapy remains to be more thoroughly investigated. Despite these successes, the failure rate of aspirin and of heparin remains high, justifying a continuing search for more potent and safe antiplatelet and antithrombotic drugs. PMID- 1892074 TI - Thrombolysis in unstable angina: results of clinical studies. AB - Ample evidence exists to support the major role of intracoronary thrombosis superimposed on a disrupted plaque in unstable angina. Consequently, thrombolytic treatment, already established to be highly beneficial in patients with acute myocardial infarction, might also be indicated in patients with unstable angina. The clinical response to thrombolytic treatment has been evaluated in several small-sized studies with inconsistent and somewhat deceiving results. Thus, the role of thrombolysis in the treatment of unstable angina is still controversial. Two ongoing large-scale, randomized, controlled trials, the Third Thrombolysis in Myocardial Infarction (TIMI III) in the United States testing recombinant tissue type plasminogen activator and UNASEM in Europe testing anisoylated plasminogen streptokinase activator complex will, it is hoped, solve the debate. At present, early thrombolysis might be considered for the treatment of the subset of patients with severe rest angina associated with transient ST-T ischemic changes. PMID- 1892075 TI - Incremental prognostic accuracy of clinical, radionuclide and hemodynamic data in acute myocardial infarction. AB - A logical sequence of testing in evaluating prognosis early in acute myocardial infarction (AMI) would be to use clinical data first, then add noninvasive data and finally add invasive data. The incremental prognostic information concerning 1-year survival obtained from such a sequence in 107 patients with AMI was studied using logistic regression and receiver-operating characteristic curves. Cardiac mortality was 24% at 1 year. Clinical data obtained soon after admission (prior myocardial infarction, heart rate, blood pressure, age) were 78 +/- 5% accurate in the prediction of 1-year survival. The addition of radionuclide estimated left ventricular ejection fraction or invasive hemodynamic data to the clinical model at this time improved prognostic accuracy to 84 +/- 5% (p = 0.05) and 87 +/- 4% (p = 0.007), respectively. The further addition of invasive data to the model containing clinical and left ventricular ejection fraction data provided a further increment in prognostic accuracy to 89 +/- 4%, whereas no significant increase in accuracy was seen on addition of left ventricular ejection fraction to the model containing clinical and invasive data. It is concluded that clinical data provide important prognostic information concerning late survival early in the course of AMI. This may be improved by the logical application of noninvasive and invasive studies at this time. PMID- 1892077 TI - Beat-to-beat electrocardiographic morphology variation in healed myocardial infarction. AB - Using high-fidelity electrocardiographic (ECG) amplifiers, we measured subtle beat-to-beat ECG morphologic variations at different phases of the ECG complex. The electrocardiograms were recorded from 49 men with a documented Q-wave myocardial infarction and from 30 age-matched normal men. Forty consecutive beats were averaged to achieve an average ECG signal from which variance could be calculated. The relative variance, defined as the ratio between the integrated variance of the examined window and the integrated variance of the ECG signal that was close to full cycle length, was calculated at QRS onset and at offset in 2 frequency bands (4 to 40 and 60 to 120 Hz). Patients with healed infarction had a relative variance of 2.1 +/- 0.5 (mean +/- standard deviation [SD]) at QRS offset (a window of 40 ms), which was significantly lower than that of the healthy volunteers: 2.5 +/- 0.33 (mean +/- SD; p less than 0.02) at the low frequency band. At the high-frequency band, patients with healed infarction had a significantly higher relative variance than the control subjects at QRS onset: 1.95 +/- 0.58 vs 1.55 +/- 0.35 (mean +/- SD; p less than 0.005). A model based on the numerous minor conduction abnormalities that exist in the chronically ischemic myocardium is presented to explain the changes in variance at the onset and offset of the QRS. The variance changes described can eventually serve as quantitative indexes of myocardial injury and electrical stability in patients with ischemic heart disease. PMID- 1892076 TI - Effects of early captopril administration on infarct expansion, left ventricular remodeling and exercise capacity after acute myocardial infarction. AB - In a double-blind study, 99 patients (82 men, age range 40 to 75 years) with acute myocardial infarction (AMI) were randomly assigned to receive captopril or placebo. Treatment began within 24 hours of admission. Serial echocardiographic measurements of endocardial segment lengths and left ventricular (LV) volumes, and ejection fractions were obtained. The 2 groups were matched at baseline except for an excess of previous AMI in the placebo group (13 of 50 vs 2 of 49 patients, p = 0.002). The increase in anterior segment length, from baseline to 2 months, was significantly less in the captopril than in the placebo group (2.8 +/ 1.6 vs 10.4 +/- 2.4mm, 95% confidence interval [CI] -13.5 to -1.7, p = 0.01). The increase in posterior segment length was also less in the captopril group, but the difference was not significant (3.2 +/- 1.2 vs 7.0 +/- 1.8mm, 95% CI -8.0 to 0.5, p = 0.08). Fewer patients in the captopril group demonstrated increases in segment length greater than 2 standard deviations of the measurement error (14 of 70 [20%] vs 29 of 72 [40%] patients, p = 0.009). In patients with anterior AMI, the infarct-containing anterior segment length increased by 4.5 +/- 2.3 mm in the captopril versus 12.4 +/- 3.1 mm in the placebo group (95% CI -15.7 to 0.2, p = 0.046), and fewer patients in the captopril group demonstrated infarct expansion (6 of 20 [30%] vs 13 of 21 [62%] patients, p = 0.04).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1892078 TI - Significance of silent myocardial ischemia during exercise testing in patients with diabetes mellitus: a report from the Coronary Artery Surgery Study (CASS) Registry. AB - To evaluate the significance of ischemic ST depression without anginal chest pain during exercise testing among patients with diabetes mellitus, the data on 45 such patients from the Coronary Artery Surgery Study registry were analyzed. These patients (group 1, silent ischemia) were compared with 37 diabetic patients with both ischemic ST depression and chest pain (group 2, symptomatic ischemia), with 31 diabetic patients without ischemic ST depression or chest pain (group 3, no ischemia), and with 429 patients without diabetes who had silent ischemia during exercise testing. All patients had documented coronary artery disease (CAD) (greater than 70% diameter narrowing). The 6-year survival among patients with silent ischemia was worse in diabetic than nondiabetic patients (59 vs 82%, respectively, p less than 0.001). By contrast, the 6-year survival among patients without ischemia was similar among diabetic and nondiabetic patients (93 vs 85%, respectively, p = 0.476). Among diabetic patients, survival at 6 years with medical treatment was 59% for group 1, 66% for group 2 and 93% for group 3 (p = 0.008). Survival among subsets of patients with diabetes and silent ischemia (group 1) based on the extent of CAD and left ventricular function ranged from 100 to 32% (p = 0.093). The survival of the 45 patients with diabetes mellitus and silent ischemia (group 1) treated medically was compared with that of 28 patients receiving coronary artery graft bypass surgery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1892080 TI - Efficacy and safety of intravenous and oral propafenone in pediatric cardiac dysrhythmias. AB - Propafenone was administered to 58 patients with a mean age of 3.2 years (range 0.1 to 16). Mean intravenous dose was 1.2 mg/kg body weight (range 0.3 to 1.5 mg). The final mean oral maintenance dose was 308 mg/m2 body surface area (range 200 to 600 mg/m2, 16.8 mg/kg body weight). After intravenous application, propafenone was effective in 21 of 36 patients; atrial flutter was converted in 1 of 5 patients, and reentry supraventricular tachycardia was controlled in 15 of 25 patients. Propafenone was partially or completely effective in 3 of 4 patients with chaotic atrial tachycardia. Junctional ectopic tachycardia was suppressed in 2 infants. Thirty-seven patients had oral treatment with a mean follow-up of 2.2 years. Propafenone was effective in 33 of 37 patients (89%); atrial flutter was controlled in 2 patients, ventricular ectopy was suppressed in 1 of 2 patients. In reentry supraventricular tachycardia, propafenone was effective in 25 of 28 patients. Chaotic atrial tachycardia (n = 3) and junctional ectopic tachycardia (n = 2) were controlled after successful intravenous therapy. Systemic side effects were rare. Two patients developed a proarrhythmic effect, and 1 patient with ventricular ectopy after repair of tetralogy of Fallot died suddenly during propafenone maintenance therapy. PMID- 1892079 TI - Asymptomatic myocardial ischemia during percutaneous transluminal coronary angioplasty and importance of prior Q-wave infarction and diabetes mellitus. AB - Eighty-eight patients undergoing percutaneous transluminal coronary angioplasty (PTCA) of 100 stenoses were studied for the presence of factors deemed significant in the etiology of silent myocardial ischemia. Thirty-two patients were asymptomatic during balloon dilations of 36 arteries, and 56 patients had angina during PTCA of 64 arteries. There were no differences in age, sex, prior anginal history, antianginal regimen, extent of coronary artery disease and number or duration of inflations between the 2 study groups. Previous infarction (33 vs 12%, p less than 0.02), Q waves in the target area (31 vs 7%, p less than 0.005) and diabetes mellitus (36 vs 17%, p less than 0.05) were present more often in the asymptomatic group. Sixty-four% of all asymptomatic patients had either diabetes or previous infarction in the target territory. Collateral circulation was more frequent in asymptomatic patients, probably reflecting the ability of collateral arteries to ameliorate ischemia. During 2-vessel PTCA, patients without angina during dilation of only 1 of the 2 treated arteries (discordant responders) had previous infarction in that artery's territory (5 of 5, 100%), whereas patients without previous infarction were either symptomatic or asymptomatic (concordant responders) during PTCA of both arteries. This study shows that asymptomatic ischemia occurs frequently during PTCA in patients with symptomatic coronary disease. Prior Q-wave infarction and diabetes mellitus are important, independent factors associated with painless ischemia. It is suggested that infarction produces a localized dysfunction of afferent cardiac pain fibers, whereas diabetes can cause a global cardiac sensory neuropathy. PMID- 1892081 TI - Complex ventricular ectopic activity in patients less than 20 years of age with or without syncope, and the role of ventricular extrastimulus testing. AB - To assess the potential for ventricular tachycardia (VT), ventricular extrastimulus testing was performed in 33 young patients with complex ventricular ectopic activity defined as multiform ventricular premature complexes (VPCs), couplets or nonsustained VT, or a combination, found during electrocardiographic monitoring. There were 21 male and 12 female patients with a mean age of 11 years (range 1 to 18). Patients were divided into 2 groups based on the presence (14 patients) or absence (19 patients) of syncope. Patients with syncope had ostensibly normal hearts (9 patients) or miscellaneous heart disease (5 patients). Patients without syncope had ostensibly normal hearts (8 patients) or miscellaneous heart disease (11 patients). Ventricular stimulation protocol consisted of burst pacing and 1 to 4 programmed extrastimuli decreasing to refractoriness at 3 drive-train cycle lengths, and at 2 pacing sites (right ventricular apex and outflow tract) during the drug-free baseline state and isoproterenol infusion. No patient had VT induced with 1 or 2 extrastimuli. VT was induced in 13 of 14 patients (93%) with syncope, and in 9 of 19 patients (47%) without syncope (p less than 0.05). Using a 3-extrastimuli protocol, 8 of 14 patients (57%) with and 3 of 19 patients (16%) without syncope had VT induced (p less than 0.05). These findings suggest that VT may be the cause of syncope in young patients with complex ventricular ectopic activity. PMID- 1892082 TI - Quantitative analysis of signal-averaged P waves in idiopathic paroxysmal atrial fibrillation. AB - Detailed analysis of the QRS complex can identify patients at risk from ventricular arrhythmias, but similar techniques applied to the atria have been disappointing. This study attempts to quantitate differences in the fine morphology of P waves in a group of 9 patients with paroxysmal atrial fibrillation (AF) versus 15 control subjects. Atrial triggered signal-averaging was combined with a detailed investigation of P-wave duration, high-frequency spatial voltage and spatial velocity. Signal-averaged P-wave duration was significantly increased in patients with paroxysmal AF (135 +/- 8 vs 126 +/- 4 ms, p less than 0.05). The root-mean-square voltage at frequencies greater than 35 Hz in these patients was also significantly greater (16 +/- 3 vs 12 +/- 1 microV, p less than 0.05). Similar observations were made at frequencies greater than 40 Hz (10 +/- 3 vs 7 +/- 1 microV, p less than 0.05). These differences appeared to be confined to the third quarter of the P wave (third quarter root mean-square voltage at greater than 40 Hz expressed as a ratio of total P-wave root-mean-square voltage, 1.4 +/- 0.1 vs 1.2 +/- 0.1, p = 0.005). Spatial velocity was also increased in the paroxysmal AF group (peak spatial velocity 6.4 +/- 1.8 vs 4.6 +/- 0.5 mV/s, p less than 0.05). These observations support previous intracardiac data that implicate delay and fragmentation of intraatrial conduction in the pathogenesis of paroxysmal AF. PMID- 1892083 TI - Diagnostic accuracy of exercise thallium-201 single-photon emission computed tomography in patients with left bundle branch block. AB - Recent reports have proposed that abnormal apical or anterior wall perfusion with exercise thallium-201 imaging may increase diagnostic accuracy for disease of the left anterior descending artery in patients with left bundle branch block (LBBB). To evaluate these suggestions, 83 patients with LBBB who underwent thallium-201 single-photon emission computed tomography and coronary angiography within an interval of 3 months were retrospectively reviewed. There were 59 men and 24 women aged 33 to 84 years (mean 65). Myocardial perfusion to the apex, anterior wall and anterior septum were scored qualitatively by consensus of 2 experienced observers and by quantitative analysis in comparison with a normal data base. The sensitivity, specificity and accuracy of perfusion defects in these segments were then expressed according to angiographic findings. Significant stenosis of vessels within the left anterior descending artery territory was present in 38 patients. By receiver-operator characteristic analysis, a fixed or reversible defect within the apex by the qualitative method was the best criterion for coronary artery disease. However, although highly sensitive (79 and 85% by the qualitative and quantitative methods, respectively), an apical defect was neither specific (38 and 16%, respectively), nor accurate (57 and 46%, respectively). Perfusion abnormalities in the anterior wall and septum were also of limited diagnostic accuracy. Thus, modified interpretative criteria in patients with LBBB are not clinically useful in the assessment of left anterior descending artery disease. PMID- 1892084 TI - Adrenergic hypersensitivity after beta-blocker withdrawal in hypertrophic cardiomyopathy. AB - Withdrawal of beta-blocker therapy has been associated with the development of adrenergic hypersensitivity and adverse clinical effects in patients with coronary artery disease and hypertension. The aim of this study was to establish the occurrence and clinical significance of adrenergic hypersensitivity after abrupt withdrawal of long-term beta blockade in hypertrophic cardiomyopathy. Beta adrenergic sensitivity was measured using the isoprenaline chronotropic dose25. Symptom assessment chronotropic dose25 calculation, bicycle exercise, echocardiography and Holter monitoring were performed while the patient received beta-blocker therapy and repeated on days 2, 4, 6, 8 (acute withdrawal period) and on day 21 after abrupt withdrawal. The study was terminated after 7 patients had been studied because all patients experienced a marked deterioration in symptoms and several clinical events had occurred. The chronotropic dose25 (mean +/- standard deviation) demonstrated beta 1-adrenergic hypersensitivity with a minimal value of 1.6 +/- 0.8 micrograms during the acute withdrawal period compared with 3.8 +/- 1.7 micrograms on day 21 (p = 0.003). Heart rates during rest and exercise showed an overshoot increase during the acute withdrawal period. The maximal 24-hour ventricular ectopic count was higher during the acute withdrawal period than during day 21 (p = 0.04). Of 3 patients with inducible outflow tract gradients, 2 developed resting gradients greater than 30 mm Hg during the acute withdrawal period. There was an increase in peak late filling velocity of mitral inflow after beta-blocker withdrawal. In conclusion, transient beta-adrenergic hypersensitivity occurs after beta-blocker withdrawal in hypertrophic cardiomyopathy and is associated with significant physiologic changes and adverse clinical consequences. PMID- 1892085 TI - Echocardiographic determination of aortic and pulmonary valve areas in subjects with normal hearts. AB - Two-dimensional and Doppler echocardiography were performed in 70 subjects (aged 1 day to 16 years, body surface area from 0.08 to 2.1 m2) to determine aortic and pulmonary valve areas in normal children and adolescents. Valve areas were determined by the continuity equation using echo-determined ventricular outflow tract diameters and Doppler-determined flow velocities from the outflow tracts and corresponding great arteries. Left ventricular outflow tract diameter ranged from 0.3 to 2.2 cm and right ventricular outflow tract diameter from 0.4 to 2.8 cm. Outflow tract diameters were linearly related to the square root of body surface area. Flow velocity increased from a mean of 0.75 m/s in the left ventricular outflow tract to 1.12 m/s in the aorta and from 0.56 m/s in the right ventricular outflow tract to 0.89 m/s in the pulmonary artery. Flow velocities were unrelated to body size. Valve areas were linearly related to body surface area (r = 0.88 and 0.80 for the aortic and pulmonary valves, respectively). Mean aortic and pulmonary valve area indexes were 1.33 cm2/m2 and 1.70 cm2/m2, respectively. The data provide normal values for echocardiographically determined valve areas and validate the practice of indexing valve area for body surface area. PMID- 1892086 TI - Circadian variation and influence of risk factors on heart rate variability in healthy subjects. AB - Quantification of variations in instantaneous heart rate (HR) can be used to evaluate cardiac autonomic function. A 24-hour standard deviation of all normal RR intervals less than 50 ms in survivors of myocardial infarction has been shown to be an independent marker of adverse prognosis. Twenty-four-hour HR variability in 140 healthy subjects aged 40 to 77 years was determined as (1) standard deviation, and (2) percentage of successive RR interval differences greater than 6%--an index of parasympathetic activity. The 24-hour standard deviation varied between 68 and 261 ms (median 139). Range for index of parasympathetic activity was 0.1 to 29.6% (median 4.4). Twenty percent of the interindividual variation in HR variability was explained by impact of risk factors. Standard deviation was uninfluenced by age, whereas parasympathetic activity decreased by increasing age. High physical training level was independently associated with significantly higher standard deviation (and parasympathetic activity) values during both day and night. Hourly figures of standard deviation decreased during the night, whereas parasympathetic activity increased and peaked early morning. Standard deviation values as low as those reported in high-risk patients were not observed, but comparable low values for, and lack of diurnal variation in, parasympathetic activity were seen in healthy subjects also. In conclusion, risk factors and, in particular, the physical training level have impact on 24-hour HR variability in healthy subjects. This may prove valuable for modification of cardiac autonomic activity in patients. PMID- 1892087 TI - Sudden death during ambulatory electrocardiographic monitoring. PMID- 1892088 TI - Prevalence of non-Q-wave acute myocardial infarction with total angiographic occlusion of the left circumflex coronary artery within eight weeks of infarction. PMID- 1892089 TI - Cardiopulmonary support increases morbidity and mortality in high-risk coronary angioplasty. PMID- 1892090 TI - Lack of pain during myocardial infarction in diabetics--is autonomic dysfunction responsible? PMID- 1892091 TI - Evidence suggesting time-dependent recovery of excitability in the in vivo human sinus node. PMID- 1892092 TI - Survival in patients declining implantable cardioverter-defibrillators. PMID- 1892093 TI - Cardiac tamponade complicating mitral balloon valvuloplasty. PMID- 1892094 TI - Effects of abstinence on alcoholic heart muscle disease. PMID- 1892095 TI - Intraoperative balloon valvuloplasty for critical aortic valvular stenosis in neonates. PMID- 1892096 TI - Still's-like innocent murmur can be produced by increasing aortic velocity to a threshold value. PMID- 1892098 TI - Libman-Sacks endocarditis mimicking intracardiac tumor. PMID- 1892097 TI - Increased lipid peroxidation in cyclosporin-treated heart transplant recipients. PMID- 1892099 TI - Usefulness of corticosteroid therapy for protein-losing enteropathy after the Fontan procedure. PMID- 1892100 TI - Balloon dilatation of a stenotic Waterston shunt with long-term follow-up. PMID- 1892101 TI - Acute myocardial infarction after ergonovine administration for uterine bleeding. PMID- 1892102 TI - Successful radiofrequency catheter ablation of accessory pathways that recurred after surgery. PMID- 1892103 TI - Atrial septal aneurysm mimicking a right atrial mass on transesophageal echocardiography. PMID- 1892104 TI - Systolic excursion of the mitral anulus as an index of left ventricular systolic function. PMID- 1892105 TI - Anticardiolipin antibody titers in patients with myocardial infarction. PMID- 1892106 TI - Natural history of cardiac rhabdomyoma. PMID- 1892107 TI - Metoprolol as antihypertensive drug. PMID- 1892108 TI - Bidirectional ST shift in ischemic right ventricle. PMID- 1892109 TI - Cocaine and myocardial infarction. PMID- 1892110 TI - What's in a name? PMID- 1892111 TI - Quantitative analysis of Wenckebach periodicity. PMID- 1892112 TI - Medical versus surgical management of intracardiac rhabdomyomas. PMID- 1892113 TI - "Anything to be done right has got to be done by people that make their living at it". PMID- 1892114 TI - Ventricular late potentials in patients with acute myocardial infarction and early thrombolytic treatment. PMID- 1892115 TI - Parental history of acute myocardial infarction and coronary artery disease in men. PMID- 1892116 TI - Anatomic and electrical correlations of the heart. PMID- 1892117 TI - Ventricular tachycardia and accelerated ventricular rhythm presenting in the first month of life. PMID- 1892118 TI - Mechanical failure of a St. Jude Medical prosthesis. PMID- 1892119 TI - Antibody HAM56 is not macrophage-specific in vein autografts. PMID- 1892120 TI - Lactic dehydrogenase. An old enzyme reborn as a cancer marker? PMID- 1892121 TI - Comparison of API Rapid Strep, Baxter MicroScan Rapid Pos ID Panel, BBL Minitek Differential Identification System, IDS RapID STR System, and Vitek GPI to conventional biochemical tests for identification of viridans streptococci. AB - Viridans group streptococci (36 stock strains and 167 single patient blood culture isolates) were assessed using API Rapid Strep, Baxter MicroScan Rapid Pos ID Panel, BBL Minitek Differential Identification System, IDS RapID STR System, and Vitek GPI methods. Identification data obtained with these systems were compared with those indicated by conventional biochemical procedures. API, Baxter MicroScan, BBL, IDS, and Vitek corresponded with conventional biochemical identification in 74%, 66%, 65%, 50%, and 61% of the isolates, respectively; using recommended supplemental tests, agreement was augmented in 9%, 11%, 20%, 11%, and 21% of the isolates, respectively. Disagreement with conventional biochemical methods occurred in 14%, 17%, 14%, 32%, and 10% of the commercial techniques, respectively; no identification was possible in 2%, 5%, fewer than 1%, 6%, and 8% of specimens, respectively. BBL, API, and Baxter MicroScan systems provided the most reliable rapid identification, although supplemental testing often was required. Until a higher percentage of correct identification data can be obtained without supplemental procedures, conventional biochemical techniques will remain the methods of choice for identification of viridans streptococci. PMID- 1892122 TI - Serum lactate dehydrogenase-3 isoenzyme in chronic granulocytic leukemia. AB - Abnormal levels of serum lactate dehydrogenase-3 (LD-3) activity were observed in 92% of patients (35 of 38) with active chronic granulocytic leukemia (CGL), in 40% of patients (4 of 10) in partial remission, and in 13% of patients (1 of 8) in complete remission. In evaluating the electrophoretic LD isoenzyme patterns of these patients, three criteria were used. In criterion-1 elevations, the LD 3/total LD ratio, expressed as a fraction of serum total LD, and LD-3 value, expressed in absolute units, were greater than the upper limit of the reference range. In criterion-2 elevations, only the LD-3/total LD ratio was greater than the upper limit of the reference range. In criterion-3 elevations, only the absolute LD-3 activity exceeded the upper limit of the reference range, and these specimens showed isomorphic elevation of all five LD isoenzymes. Use of the last of these criteria increased the clinical sensitivity of serum LD-3 elevations in active CGL from 82% to 92%. The mean serum LD-3 absolute value and serum total LD activity usually showed statistically significant differences (P less than 0.05) among patients with active CGL, those in partial remission, and those in complete remission, but did not distinguish between subgroups of individuals with active CGL. Elevation of the serum LD-5/total LD ratio in 16 of 58 patients was due to hepatic injury or methodologic imprecision, showing analytically insignificant, borderline abnormalities in all cases of active CGL. In 10 of 62 patients in complete remission or partial remission, however, such elevation was unexplained. Our results indicate that the evaluation of serum LD-3 values in both absolute and relative terms slightly increases the clinical sensitivity of LD-3, and, therefore, suggest that LD-3 might be a useful marker for CGL. PMID- 1892123 TI - The role of gene rearrangements for antigen receptors in the diagnosis of lymphoma obtained by fine-needle aspiration. A study of 63 cases with concomitant immunophenotyping. AB - To assess the efficacy of performing genotyping in addition to immunophenotyping as an adjunct to cytologic diagnosis, 63 consecutive patients with fine-needle aspirates of lymphoproliferative lesions who had concurrent immunophenotyping and genotyping performed on fine-needle aspirate cell suspensions were studied. Thirty-nine of 63 specimens (62%) that appeared to contain non-Hodgkin's lymphoma and that proved to be of B-cell lineage by genotyping were accurately phenotyped and shown to be monotypic for immunoglobulin light chains by cell suspension immunocytochemistry. Genotyping facilitated lineage assignment and/or confirmed clonality in 17 of 63 specimens (27%) that were difficult to determine based on morphologic data. These include cases of atypical lymphoid proliferations with polyclonal or inconclusive markers (n = 6), peripheral T-cell lymphoma (n = 3), extracutaneous mycosis fungoides (n = 1), lymphoblastic lymphoma (n = 4), null cell lymphoma (n = 1), and specimens with equivocal or technically unsatisfactory markers (n = 2). Based on these results, it is proposed that genotyping for lineage assignment and/or clonality be performed to include cases of atypical lymphoid proliferations, T-cell malignant neoplasms, lymphoid malignant neoplasms with equivocal markers, and differentiation of lymphoid from nonlymphoid neoplasms. Genotyping by antigen-receptor gene rearrangement appears to be redundant in cases with mature B-cell phenotypes that demonstrate monoclonality by immunophenotyping. PMID- 1892124 TI - Inflammatory pseudotumor of the spleen. Report of two cases with a review of the literature. AB - This study reports two cases of inflammatory pseudotumor of the spleen. The first case was a 57-year-old woman in whom the splenic mass was an incidental finding during evaluation for an acute abdomen due to a perforated, lithiasic gallbladder. The mass in the spleen measured 12.7 cm in greatest dimension. The second case was of a 46-year-old woman with a palpable, left upper quadrant mass. A computed tomography scan revealed a splenic mass and the spleen was removed. The mass measured 12 cm in greatest dimension. In a review of the literature, 13 examples of splenic inflammatory pseudotumor were reported. The age range was 19 to 75 years, with a median age of 50 years. The splenic lesions were either discovered incidentally or manifested by left upper quadrant discomfort and/or mass. Inflammatory pseudotumor of the spleen, although rare, is being increasingly recognized and should be considered in the differential diagnosis of mass lesions of the spleen. PMID- 1892125 TI - The platelet volume-number relationship in patients infected with the human immunodeficiency virus. AB - The pathophysiology of thrombocytopenia in the acquired immune deficiency syndrome has not been elucidated completely. Many findings in these patients are identical to those with immune thrombocytopenic purpura. However, recent findings in acquired immune deficiency syndrome patients including the effect of zidovudine on platelet count and the demonstration of ultrastructural changes and viral RNA in megakaryocytes, have suggested that the human immunodeficiency virus may directly infect megakaryocytes, and play a role in acquired immune deficiency syndrome-related thrombocytopenia. To investigate further the mechanism of decreased platelet counts in human immunodeficiency virus-infected patients, the platelet volume-number relationship and corresponding bone marrow findings in 34 patients infected with human immunodeficiency virus were studied. Parameters evaluated included platelet count and mean platelet volume; bone marrow cellularity, megakaryocyte number, and number and percentage of denuded megakaryocyte nuclei. Two thirds of the platelet counts were low, and of these 92% had an inappropriately low mean platelet volume. These individuals had a platelet-volume number relationship that is very similar to that seen in myelosuppressive disorders. In addition, more than 90% of the bone marrows from thrombocytopenic patients had either normal or decreased numbers of megakaryocytes. These observations provide additional evidence to support the hypothesis that the pathophysiology of human immunodeficiency virus-associated thrombocytopenia may be due, at least in part, to a direct effect on the megakaryocytes. PMID- 1892126 TI - Freeze substitution for histochemical and immunohistochemical analysis. PMID- 1892127 TI - Serum proteins as mortality index in elderly patients. PMID- 1892128 TI - Standardized hematology reports. PMID- 1892129 TI - Teaching safety management guidelines. PMID- 1892130 TI - A practitioner's guide to meta-analysis. AB - Describes the application to community issues of the meta-analytic research strategies increasingly used in many field of psychology. First, we highlight the potential value of meta-analysis to community research. Second, we describe six major steps involved in conducting an effective meta-analysis. These steps include formulating the initial research question(s), locating relevant studies, abstracting critical information from each study, and presenting, analyzing, and interpreting the resultant data. In this guide, the major aspects of meta analysis are discussed with particular emphasis on the procedures that are most critical to the validity of its conclusions. Greater familiarity with the techniques, issues, and potential of meta-analysis may stimulate investigators to make more effective use of this powerful approach to integrating research in community psychology. PMID- 1892131 TI - Expectations and high school change: teacher-researcher collaboration to prevent school failure. AB - Describes the multilevel outcomes of a collaborative preventive intervention for ninth-graders at risk for school failure using qualitative and quasi-experimental methods. Teachers, administrators, and researchers implemented innovative practices communicating positive expectations for low-achieving adolescents in their transition to high school. Changes were made in the practices of curriculum, grouping, evaluation, motivation, student responsibility, and relationships (in the classroom, with parents, and in the school). Both implementation and evaluation evolved as a function of collaboration. Change was promising but not uniform. Project teachers became more positive about students and colleagues, expanded their roles, and changed school tracking policies. The 158 project students, in contrast to the 154 comparison students showed improved grades and disciplinary referrals post-intervention and increased retention in school 1 year later, but their absences rose and improved performance was not maintained. The implications of this analysis for school-based interventions and its evaluation are discussed. PMID- 1892132 TI - Paradigms and the research report: making what actually happens a heuristic for theory. AB - Provided a perspective on the discrepancy between how community research is carried out and how it is reported in scholarly journals. Drawing on the description of an intervention by Weinstein and her colleagues, several criteria for the more complete reporting of community-based interventions are described. These criteria focus on the nature of the research relationship, adequate description of the social context hosting the intervention, and the active interest in intervention effects across multiple levels of analysis. PMID- 1892133 TI - I know I can do this, but where's my motivation? AB - Breadth of scope and inclusion of teachers as co-investigators made the Weinstein et al. intervention unusually powerful and well adapted to its context although its effects are difficult to interpret. Future efforts might build on this model by expanding its purview even further, particularly by including more self-report data, attending to educational aims and curricular content in addition to instructional method, addressing the value aspects as well as the expectancy aspects of motivation, and seeking to develop enduring dispositions of motivation to learn in students and autonomous goal setting in teachers. PMID- 1892134 TI - Ecological interventions and the process of change for prevention: wedding theory and research to implementation in real world settings. AB - Considers a preventive intervention effort designed to modify the characteristics and regularities of the school environment so as to enhance the expectations conveyed to high risk students. Employing this case effort (Weinstein et al., 1991) as a base, several issues are highlighted that deserve greater attention in the design, implementation, assessment, and reporting of other preventively focused social interventions. These issues include: (1) the degree of program implementation fidelity, (2) the impact a lack of attainment of program fidelity may have on arriving at erroneous evaluation conclusions about social programs, (3) the ways in which the theory and basic research employed in the program rationale is appropriate to and reflected in the program as designed, (4) issues of program potency and dosage, (5) the ways in which quantitative and qualitative evaluation data can enhance each other, and (6) the import of evaluability assessments of programs prior to moving to outcome evaluations. In addressing these issues, the importance of developmentally- and ecologically-informed program formulations is underscored. Finally, the critical role that program reports such as the Weinstein paper, with its careful discussion of both the process of implementation and outcome assessments, can play in the development of more effective prevention program implementation efforts is highlighted. PMID- 1892135 TI - Confronting the social context of school change. AB - Discusses several aspects of a case study of change in a high school setting. Suggests a distinction between prescriptive, participative, and collaborative approaches to change and argues that the collaborative approach used in this case has certain advantages over the other two approaches. Other issues considered include: the role of conflicting agendas in the change process, the importance of gaining support from district-level as well as school-level leadership, the need to consider ways of insuring maintenance of change, and the interrelationship between individual, small group, and cultural level change in educational reform. PMID- 1892136 TI - Developmental and family milieu correlates of resilience in urban children who have experienced major life stress. AB - Reports findings from interviews with parents of demographically-comparable groups of highly-stressed urban children with stress-resilient (SR) and stress affected (SA) outcomes at ages 10-12. SR and SA children were compared on family milieu and child development variables assessed within a developmental framework. Compared to SAs, parents of SRs scored higher on variables reflecting parent perceptions of a nurturant caregiver-child relationship and self-views as effective caregivers, in the context of positive discipline practices, a child's positive early temperament, and support for primary caregivers. A discriminant function analysis identified seven variables that optimally differentiated the groups and correctly classified 86% of the Ss as SR or SA. PMID- 1892137 TI - An assessment of the needs of mutual-help groups. AB - Assessed the needs of mutual-help groups in relation to how self-help clearinghouses can best assist. Most important problems centered on member involvement, attendance and recruitment, lack of public awareness, and finances. Most important needs were for greater public education and more referrals to groups. Significant differences were found across different types of organizational affiliation for the problems of recruitment of members, lack of public awareness, and problem members. The dynamic nature of mutual-help groups may naturally produce many of the turnover, attendance, and involvement problems which in turn generates the ongoing need to recruit new members in part through greater public awareness. Many of the goals and needs of mutual-help groups, coupled with the large number of group members, may lead to significant social and policy change in health and mental health services. PMID- 1892138 TI - Supportive and unsupportive responses of others to rape victims: effects on concurrent victim adjustment. AB - Evaluated the impact that actions of significant others have on adjustment following rape. Significant other behavior is conceptualized as having two dimensions--supportive behavior and unsupportive behavior--and each dimension was measured using multiple items. Unsupportive behavior, but not supportive behavior, was found to bear a significant association to victim adjustment. Implications for those who work with victims are discussed. PMID- 1892139 TI - Gastrointestinal disease associated with nonsteroidal anti-inflammatory drugs: new insights from observational studies and functional status questionnaires. PMID- 1892140 TI - Nonsteroidal anti-inflammatory drug-associated gastropathy: incidence and risk factor models. AB - PURPOSE: The most prevalent serious drug toxicity in the United States is increasingly recognized as gastrointestinal (GI) pathology associated with the use of nonsteroidal anti-inflammatory drugs (NSAIDs). The incidence of serious GI events (hospitalization or death) associated with NSAID use was therefore prospectively analyzed in patients with rheumatoid arthritis (RA) and patients with osteoarthritis. PATIENTS, METHODS, AND RESULTS: The study consisted of 2,747 patients with RA and 1,091 patients with osteoarthritis. The yearly hospitalization incidence during NSAID treatment was 1.58% in RA patients and was similar in all five populations studied. The hazard ratio of patients taking NSAIDs to those not taking NSAIDs was 5.2. The incidence in osteoarthritis may be less. The risk of GI-related death in RA patients was 0.19% per year with NSAIDs. Multivariate analyses assessing risk factors for serious GI events were performed in the 1,694 (98 with an event) RA patients taking NSAIDs at the predictive visit. The main risk factors were higher age, use of prednisone, previous NSAID GI side effects, prior GI hospitalization, level of disability, and NSAID dose. A rule is presented that allows estimation of the risk for the individual patient with RA. CONCLUSION: Knowledge of the risk factors for NSAID-associated gastropathy and their inter-relationships provides a tool for identification of the patient at high risk and for initiation of appropriate therapeutic action. PMID- 1892141 TI - The low risk of upper gastrointestinal bleeding in patients dispensed corticosteroids. AB - PURPOSE: To determine the incidence of upper gastrointestinal bleeding in patients treated with corticosteroids. PATIENTS AND METHODS: The incidence of upper gastrointestinal tract bleeding was assessed in a cohort of 19,880 patients from the Michigan Medicaid billing database with dermatitis and/or asthma treated with corticosteroids during 1980 to 1984. The frequency of upper gastrointestinal bleeding was assessed within 60 days after each corticosteroid prescription. RESULTS: The incidence of upper gastrointestinal bleeding in patients without a past history of upper gastrointestinal bleeding who were exposed to corticosteroids was only 2.8 cases per 10,000 person-months. The rate of upper gastrointestinal bleeding was notably higher in patients receiving anticoagulants and those with a prior history of upper gastrointestinal bleeding (23.0 and 15.9 cases per 10,000 person-months, respectively). CONCLUSION: Because the incidence of upper gastrointestinal bleeding in ambulatory patients treated with corticosteroids is so low, prophylactic therapy should be restricted to high-risk patients, if it is to be used at all. PMID- 1892142 TI - Weekly subcutaneous recombinant human erythropoietin corrects anemia of progressive renal failure. AB - PURPOSE: The purpose of this study was to analyze data retrospectively from our use of weekly subcutaneous recombinant human erythropoietin (rHuEPO) in predialysis and peritoneal dialysis patients with anemia. PATIENTS AND METHODS: All anemic patients with progressive renal failure (12 predialysis and seven home peritoneal dialysis) in whom subcutaneous rHuEPO therapy was begun at, or was reduced to, a weekly dose were studied retrospectively. Patients were not selected for, nor excluded from, these observations for any other reason. Hematocrit and endogenous creatinine clearance were monitored regularly, and no other new treatment for anemia was given except oral iron. Iron-deficiency anemia was considered improbable because of normal red blood cell mean corpuscular volume. Unfortunately, iron parameters were not monitored. RESULTS: The hematocrit increased 4 to 9 percentage points in 4 to 13 weeks in all but two patients who were initially treated with weekly doses, and a hematocrit of 31% was achieved in these patients within 6 to 12 weeks. The mean effective dose to accomplish this was 150 U/kg. All but three patients could be maintained on weekly doses at a hematocrit of 31% or higher. The mean effective dose was 75 U/kg. CONCLUSION: It is concluded that subcutaneous rHuEPO administered weekly can correct the anemia of predialysis and peritoneal dialysis patients. Weekly dosing is more convenient for patients and may be less costly for Medicare providers. PMID- 1892143 TI - Niacin revisited: clinical observations on an important but underutilized drug. AB - STUDY OBJECTIVE: To evaluate the efficacy and side effects of niacin therapy in dyslipidemic individuals. DESIGN: A retrospective analysis of patients' charts. SETTING: An outpatient referral-based clinic specializing in the treatment of lipid disorders. PATIENTS: All patients with dyslipidemia treated by niacin (n = 82) at the Atherosclerosis Detection and Prevention Clinic during 1987 to 1990, including a subgroup of 17 dyslipidemic heart transplant recipients. RESULTS: Niacin was well tolerated in 83% of the nontransplant group (n = 65) at an average dose of 2.5 +/- 0.9 g/day. Similar beneficial lipoprotein effects were found in the transplant and nontransplant patients. The high-density lipoprotein cholesterol (HDL-C) response to niacin therapy was independent of the baseline (HDL-C level. In the transplant group, 11 patients (65%) discontinued treatment, primarily because of hyperglycemia; this was especially prominent in those patients with pretreatment diabetes mellitus. Of the 15 patients using sustained release niacin, eight cases of hepatitis were recorded, some during therapy with relatively low niacin doses. Several different sustained-release preparations were responsible for this phenomenon, suggesting that the cause was not a contaminant in the preparation. No cases of hepatitis were documented in the 67 patients using regular niacin. One case of hepatitis was recently observed in a patient who switched from one type to regular niacin to another; however, we have data to suggest that the substituted preparation was not an immediate-release niacin. A familial predisposition to hepatitis is suggested by the occurrence of this side effect in identical twin brothers and two sisters. A pharmacy survey disclosed that most pharmacists are unaware of the relationship of sustained release niacin to hepatitis, have a negative impression of regular niacin, and do not stock this formulation. Finally, we found that in this small sample of patients, niacin used with lovastatin is a particularly effective drug combination and appears to have few side effects beyond those seen with niacin alone. CONCLUSIONS: Our experience supports the fact that regular niacin is a useful lipid-modifying drug. When used appropriately, patients can usually tolerate adequate doses for prolonged periods and achieve meaningful results. However, this requires a certain amount of physician skill and patient motivation. The use of sustained-release preparations to overcome this problem can lead to harmful consequences and should only be done under strict medical supervision. In our opinion, the availability of sustained-release niacin as a nonprescription drug is unjustified and should be reexamined. Finally, we have observed that reduction of very-low-density lipoprotein cholesterol (VLDL-C) with niacin alone leads to an elevation in low-density lipoprotein cholesterol in many patients; this indicates to us that the mechanism whereby niacin lowers VLDL-C and total cholesterol is not solely the result of a decreased synthesis of VLDL C. PMID- 1892144 TI - Increased all-cause and cardiac morbidity and mortality associated with the diagonal earlobe crease: a prospective cohort study. AB - PURPOSE: To ascertain whether the diagonal earlobe crease (ELC) is associated prospectively with future death or cardiac events over 8 years of follow-up in two sets of patients: those with known coronary artery disease (CAD) and those without evidence for CAD. PATIENTS AND METHODS: We performed a prospective, observational study of 108 patients in four cohorts (each matched for age, sex, and race, but differing in the presence or absence of both a diagonal ELC and CAD in 1979 to 1982). Follow-up information was gathered by telephone interviews, and dates and causes of death were determined by reference to death certificates (n = 48), hospital records (n = 9), or attending physician statements (n = 1). RESULTS: During 8 to 10 years of follow-up, 58 of the patients had died. Patients with ELCs had poorer survival rates than those without creases, by stratified log rank test (p = 0.006 for the cohorts thought not to have CAD, and p = 0.058 for those with CAD). Cardiac death rates (due to acute myocardial infarction, "sudden cardiac death," or heart failure) were also higher for patients with ELCs: 8.0 versus 0.9 cardiac deaths per 100 patient-years (p less than 0.001) in patients without CAD at entry, and 11.7 versus 3.7 cardiac deaths per 100 patient-years (p = 0.008) in patients with CAD in 1979 to 1982. Cardiac event rates (cardiac death, nonfatal myocardial infarction, or coronary artery bypass surgery) were also higher in those with ELCs: 10.4 versus 1.4 events per 100 patient-years (p less than 0.001) for those without known CAD, and 15.8 versus 5.7 events per 100 patient-years (p = 0.009) for those with CAD. CONCLUSION: These results suggest that a diagonal ELC is associated with increased all-cause and cardiac morbidity and mortality. Patients with ELCs may be at higher risk for coronary events, and might be especially cautioned to control or reduce other cardiac risk factors, even if currently without diagnostic evidence of CAD. PMID- 1892145 TI - The do-not-resuscitate order: a comparison of physician and patient preferences and decision-making. AB - PURPOSE: The purpose of this study was to compare the decision-making and preferences regarding do-not-resuscitate (DNR) orders of a group of family physicians with a group of out-patients from a family practice center. Complete results of the outpatient questionnaire were published in a previous study by the authors. SUBJECTS AND METHODS: A random sample of 202 members of the Michigan Academy of Family Practice and all 32 members of the University of Michigan Department of Family Practice were surveyed by a mailed questionnaire. The questionnaire was divided into five parts: demographics, past experiences with DNR orders, who should be involved in DNR decision-making, values clarification, and a series of scenarios matched by a variety of biomedical and non-biomedical factors. RESULTS: After eliminating physicians who had left no forwarding address or who had retired or died, the overall response rate was 61.8%. Most physicians (97%) had at some time written a DNR order for one of their patients; discussions most commonly took place in the hospital room. Physicians, like patients, thought that in addition to the patient, DNR decisions should involve the spouse, the physician, and the patient's children, respectively. Value clarification revealed that both groups most highly value "being able to think clearly" and "being treated with dignity." The presence of a number of quality-of-life issues (age, drug or alcohol use, wheelchair use, dementia, and severe pain) in a series of scenarios negatively affected the decision of both family physicians and patients to resuscitate. CONCLUSION: There are significant similarities and differences in the way physicians and patients make DNR decisions. It is important that physicians and their patients communicate in a timely manner about prognosis, values, and quality-of-life issues in order to make effective DNR decisions. PMID- 1892147 TI - Elevated cerebrospinal fluid pressures in patients with cryptococcal meningitis and acquired immunodeficiency syndrome. AB - Increased intracranial pressure has been a noteworthy problem in some of our patients with cryptococcal meningitis and acquired immunodeficiency syndrome (AIDS), and this appears to be a feature observed in patients with cryptococcal meningitis reported in the literature. Whereas most attention of clinicians is presently focused on optimizing the antifungal regimen, so as to improve on high failure rates in cryptococcal meningitis in AIDS, little attention has been paid to the problem of intracranial hypertension. We argue that visual loss and some of the cases of death early after the onset of chemotherapy may be related to high cerebrospinal fluid (CSF) pressure, regardless of antifungal therapy. The possible pathophysiologic mechanisms are discussed, and we postulate that the mechanism is reduced CSF outflow possibly due to increased outflow resistance, not necessarily accompanied by prominent cerebral edema. Optimal therapy of this complication is not yet established, but some measures that may be helpful are ventricular shunting, frequent high-volume lumbar punctures, and possibly glucocorticoids. PMID- 1892146 TI - Oral ofloxacin for the treatment of acute bacterial pneumonia: use of a nontraditional protocol to compare experimental therapy with "usual care" in a multicenter clinical trial. AB - PURPOSE: This multicenter study was designed to compare an exclusively oral regimen with "usual care" in patients hospitalized with acute bacterial pneumonia. PATIENTS AND METHODS: One hundred forty-seven patients were enrolled. All patients presented with a clinical picture consistent with pneumonia: (1) clinical symptoms of a lower respiratory tract infection, such as chest pain, cough, and production of purulent sputum; (2) roentgenographic infiltrate compatible with acute infection; and (3) Gram's stain of purulent sputum or other appropriate bronchopulmonary specimen containing gram-negative organisms, staphylococci, or pneumococci. All patients required hospitalization. The design was a parallel-group, open-label study with randomization in blocks of four. Ofloxacin, a new fluoroquinolone antimicrobial agent, was administered orally or by nasogastric tube, 400 mg every 12 hours. This was compared with the individual investigator's best selection of therapy that was administered parenterally, at least initially. RESULTS: One hundred thirty-three patients were evaluable after exclusions for deviation from protocol, early death due to unrelated causes, incorrect diagnosis, or early adverse drug reactions. All 69 patients treated with ofloxacin and 61 of 64 control patients had favorable clinical and microbiologic responses. There were no statistically significant differences between the groups in terms of demographics, therapeutic outcome, and duration of therapy. There were few side effects overall and rates were similar for the two groups. CONCLUSIONS: An exclusively oral regimen, in this case ofloxacin, may be substituted for parenteral therapy in selected patients with pneumonia. This might significantly reduce costs and risks to the patient. PMID- 1892148 TI - Double trouble, boil and bubble. PMID- 1892149 TI - In a stew. PMID- 1892150 TI - Aortoesophageal fistula: a comprehensive review of the literature. AB - Aortoesophageal fistula (AEF) is a relatively rare but life-threatening cause of upper gastro-intestinal bleeding. The clinical characteristics of AEF are so unique that a presumptive bedside diagnosis can be made at the time of presentation. In the past decade, surgical management has improved to the point that cure is now possible. For these reasons, we have reviewed the literature. We summarize our findings with respect to the etiology and clinical characteristics of AEF. Further, we discuss the diagnostic modalities that may be used to confirm the diagnosis, and the therapeutic modalities available to slow the hemorrhage, so as to allow time to correct the anatomic defect. PMID- 1892151 TI - Syndrome of severe skin disease, eosinophilia, and dermatopathic lymphadenopathy in patients with HTLV-II complicating human immunodeficiency virus infection. AB - Two intravenous drug users dually infected with human immunodeficiency virus type 1 (HIV-1) and human T-cell leukemia virus type II (HTLV-II) developed an unusual severe dermatitis characterized by progressive brawny induration, fissuring, and ulceration of the skin, with an associated CD8 cell infiltration in one patient. Both patients had persistent eosinophilia. Lymph node biopsy revealed dermatopathic lymphadenopathy, an unusual pathologic finding in HIV-1 infection but one seen in association with mycosis fungoides and other skin disorders. Two new isolates of HTLV-II virus were established from these patients and were identified as HTLV-II by Southern blotting. This type of skin disease and lymph node pathology has not been found in other intravenous drug users who have been infected with HIV-1 alone or in patients in other risk groups for HIV-1 infection. HTLV-II may play a role in this unique new disease pattern in patients infected with HIV-1. PMID- 1892152 TI - Mycobacterium fortuitum presenting as an asymptomatic enlarging pulmonary nodule. AB - A case of Mycobacterium fortuitum presenting as an asymptomatic enlarging pulmonary nodule is described. This case is unusual because the patient was female, did not have underlying pulmonary disease, was not immunocompromised, had no evidence of dissemination, and had no history of aspiration or diabetes mellitus. The patient underwent thoractomy for resection of the pulmonary nodule, which led to the diagnosis. She recovered fully and is doing well without chemotherapy. PMID- 1892153 TI - Procainamide-induced pleural fibrosis. PMID- 1892154 TI - Phenazopyridine-induced sulfhemoglobinemia: inadvertent rechallenge. PMID- 1892155 TI - Treatment of cyclic neutropenia with very low doses of GM-CSF. PMID- 1892156 TI - Intravenous immunoglobulin treatment of chronic fatigue syndrome. PMID- 1892158 TI - Neuroleptic malignant syndrome versus malignant hyperthermia. PMID- 1892157 TI - Pulse cyclophosphamide therapy for Wegener's granulomatosis. PMID- 1892159 TI - Invisible links. PMID- 1892160 TI - Managing stress. PMID- 1892161 TI - How women's work is made 'invisible'. PMID- 1892162 TI - View from the other side. PMID- 1892164 TI - Analyzing blood exposure risk. PMID- 1892163 TI - Her only chance. PMID- 1892165 TI - Nurses vote for the most valuable new drugs. PMID- 1892166 TI - When the pancreas self-destructs. PMID- 1892167 TI - How do you spell assessment? PMID- 1892168 TI - Northeast jobfocus. The new look in nursing documentation. PMID- 1892169 TI - The sorrow and the pity of Final Exit. PMID- 1892170 TI - Boston jobfocus. Nursing in Boston: a learning experience. PMID- 1892171 TI - Decision nears on AIDS testing of 'exposure-prone' providers. PMID- 1892172 TI - Embryonic ultrasonographic measurements: crown-rump length revisited. AB - New endovaginal probes will result in many investigators reexamining the crown rump length data first generated with static arm and abdominal real-time scanners. As new tables are produced, only through better understanding of the anatomy of early embryos can we realize what we are actually seeing and measuring (or at least attempting to measure). Furthermore, as we try to correlate early embryonic size with gestational age, we realize that the crown-rump measurement is not applicable in principle or in nomenclature when the embryo is less than 18 mm long. When first seen, the embryo is relatively straight; a measurement of its size is best described as "greatest length." As the embryo curves into a C shaped, tadpolelike structure, the greatest measurement along the long axis is actually a neck-rump measurement. Further unfolding of the head and regression of the tail finally allow an accurate crown-rump measurement (at about 18 mm) as we have used it for almost two decades. Early embryonic stages and characteristics are reviewed and methods of measurement of early embryonic size are explained. PMID- 1892173 TI - Ovarian cancer screening: potential effect on mortality. AB - Serum tumor markers and ultrasonography are being investigated as possible ovarian cancer screening tests. Data from the United States on ovarian cancer incidence and survival were used to estimate the potential benefit on ovarian cancer mortality from screening tests of various sensitivities. A test with 80% sensitivity could reduce ovarian cancer mortality by 50% if all screening detected cases were to experience current stage I survival rates; the benefit would be greatest among women aged 45 or older. For each cancer detected there would be at least 50 false-positive screening tests unless test specificity is greater than 98%. If our most optimistic assumptions about screening could be met, then universal periodic screening of women aged 45 to 74 would result in about 5000 additional 5-year survivors of ovarian cancer annually. Uptake of existing screening tests is far less than universal; thus we would expect the impact of any ovarian cancer screening program to fall short of these projections. PMID- 1892174 TI - Prenatal behavioral risk screening by computer in a health maintenance organization-based prenatal care clinic. AB - Cigarette smoking, alcohol and drug abuse, and stressful life events are significant contributors to prematurity and low birth weight in the United States. Identification and treatment of pregnant women with these risk factors require obtaining complete and accurate psychosocial histories. The purpose of this study was to determine whether a computer interview developed by our staff is appropriate for assessing behavioral risk factors for adverse pregnancy outcomes and for educating pregnant women about healthy behaviors during pregnancy. This computer interview asks about pregnant patients' perceived life stressors, diet, use of cigarettes and alcohol, and abuse of drugs. The study population consisted of 201 medically insured Hispanic and non-Hispanic white women attending a health maintenance organization--based prenatal clinic. Almost all subjects rated the computer interview favorably. Medical record reviews were conducted to compare participants' reports of cigarette, alcohol, and drug use obtained from paper-and-pencil interviews with behaviors reported during the computer interview. Although self-reported rates of smoking did not differ between the two interview techniques, a much higher percentage of women reported alcohol and drug use during the computer interview. Study participants scored significantly higher on a test measuring knowledge of the effects of stress, diet, and substances of abuse on pregnancy than did a control group. Results demonstrated the potential value of computer-interactive software programs for assessing high-risk behaviors among pregnant women in this population and educating them about healthy behaviors during pregnancy. PMID- 1892175 TI - Short-term variation in abnormal antenatal fetal heart rate records. AB - In a retrospective study the relation of reduced fetal heart rate variation to fetal acidemia was analyzed with a computerized system for numeric analysis. Between 1983 and 1987, 78 pregnancies were identified in which at least one record of the fetal heart rate had very low long-term variation. The outcome was analyzed to determine the numeric criteria of fetal heart rate variation that most efficiently detect a fetus that will die (preterminal) or is dying (terminal). Because fetal compromise was found on occasion to be associated with a slow sinusoidal fetal heart rate rhythm that increased measures of long-term variation. It was necessary to define a new index of short-term fetal heart rate variation (the 1/16 minute epoch-epoch variation). This was closely related to long-term variation (r = 0.9) but provided better detection of preterminal records as judged by metabolic acidemia at delivery or intrauterine death. PMID- 1892176 TI - Maturation of the uterine cervix by repeated intracervical instillation of prostaglandin E2. AB - An attempt was made to ripen the uterine cervix in 100 high-risk pregnancy patients (pregnancy between 34 to 41 weeks' gestation), with the use of intracervical instillations of 0.25 mg of prostaglandin E2 mixed with a tylose gel. The maturation process was repeated every 48 hours. Forty-nine patients were delivered of infants after the first maturation and 51 patients required between two and nine instillations. In patients requiring multiple instillations, the mean delay between the first procedure and delivery was 9 +/- 4 days (range, 2.4 to 16 days). Among the 59 nulliparous women, only 23 were delivered of infants after a single maturation and 36 required multiple maturations (p less than 0.02). When the group of patients who were delivered of infants after a single maturation process was compared with the group requiring multiple maturations, no difference could be seen with regard to age, term of pregnancy, or Bishop cervical score at the time of inclusion in the study. The myometrial activity and the onset labor induced by prostaglandin E2, were similar in both groups. Fetal heart rate decelerations occurred in 16.3% (8/49) of the patients with single maturations and in 17.6% (9/51) of the patients who required multiple maturations. The outcome of the pregnancy and the rate of cesarean sections (24% and 27%) were similar in both groups. No patients required cesarean sections because of failed induction of labor. Cervical ripening after repeated applications of 0.25 mg of prostaglandin E2 seems to be safe for the fetus, providing that the patient is closely supervised. PMID- 1892177 TI - Hypoplastic left heart syndrome: prenatal diagnosis, clinical profile, and management. AB - We diagnosed hypoplastic left heart syndrome, generally regarded as a lethal congenital heart defect, by fetal echocardiography in 20 pregnancies in the last 5 years. The clinical profile, management, and outcome of these pregnancies were reviewed. We found a 40% association of karyotype and extracardiac malformations. Elective abortion was performed in nine pregnancies. Two of seven live-born babies had early neonatal assessment and intervention as a result of in utero diagnosis and counseling. Prolonged survival was achieved in both infants. We conclude that prenatal diagnosis of the hypoplastic left heart syndrome necessitates complete evaluation of the fetus for associated genetic and extracardiac malformations. Prenatal diagnosis of this defect provides opportunities for in depth counseling of parents and obtaining informed consent for either postnatal intervention or nonintervention before the medical and emotional complexities associated with the neonatal intensive care setting are encountered. PMID- 1892178 TI - Management of fetal hemolytic disease by cordocentesis. I. Prediction of fetal anemia. AB - Between January 1985 and November 1990, 128 pregnancies complicated by maternal red blood cell alloimmunization were referred to our Fetal Diagnosis and Treatment Unit. We examined the premise that an evaluation of fetal blood would accurately identify fetuses at risk of requiring antenatal transfusion therapy. Two hundred seventy-two diagnostic cordocenteses were performed. Criteria for the timing of repeat cordocenteses were developed retrospectively on the basis of the fetal hematocrit values, reticulocyte counts, and direct Coombs' test results of the first 84 pregnancies. These criteria were tested and confirmed prospectively on the next 44 pregnancies. On the basis of the first blood sample, four hematologic patterns (and their distributions) were identified in the 98 antigen positive fetuses. Pattern 1: fetuses at low risk of having significant antenatal anemia (hematocrit less than 30%) (n = 11, 11%). These fetuses had normal hematocrit values and reticulocyte counts coupled with negative or trace-positive direct Coombs' test. No fetus in this group had significant antenatal anemia. Pattern 2: fetuses at intermediate risk of having anemia (n = 29, 31%). Pattern 2 fetuses had normal hematocrit values and either direct Coombs' titers of more than trace less than or equal to 2+ and normal reticulocyte counts or low reticulocyte counts (less than 2.5th percentile for gestation). Twenty-one percent (n = 6) of fetuses in pattern 2 had significant antenatal anemia. Patterns 3 and 4: fetuses at greatest risk of having severe anemia. These fetuses had normal hematocrit values associated with either reticulocyte counts greater than 97.5th percentile for gestation or a direct Coombs' test greater than or equal to 3+ (pattern 3, n = 49, 50%) or both, or a mild anemia (greater than 30% but less than 2.5th percentile for gestation) (pattern 4, n = 9, 10%). Eighty percent (n = 39) of fetuses with pattern 3 and 90% (n = 8) with pattern 4 developed a hematocrit value less than 30%. We conclude that evaluation of fetal hemolytic disease with a fetal blood specimen permits the identification of fetuses at high risk of having antenatal anemia. PMID- 1892179 TI - Steroid therapy for hydrops associated with antibody-mediated congenital heart block. AB - Evaluation of fetal bradycardia noted during a routine prenatal visit at 24 weeks' gestation in a mother without symptoms showed an antibody-mediated heart block with anti-La (SSB) antibody present. The fetus had a pericardial effusion and ascites. After maternal steroid therapy, the ascites resolved and the pericardial effusion was substantially diminished. Steroid therapy may be a helpful adjunct for treatment of a premature infant with hydrops as a result of antibody-mediated heart block. PMID- 1892180 TI - Prognostic factors and complication rates for cervical cerclage: a review of 482 cases. AB - Charts from 482 singleton pregnancies undergoing cerclage placement in patients over a 6-year period were reviewed. Cervical dilatation at time of surgery, number of previous spontaneous losses, and gestational age at placement were key determinants of outcome. The most frequent complication, premature rupture of the membranes, ultimately occurred in 38% of patients. The 6.6% infection rate was increased in patients undergoing emergent versus elective surgery (12.7% vs 4.7%, p less than 0.005) and in patients at increased dilatation at time of surgery (5.7% for less than or equal to 2 cm vs 41.7% for greater than 2 cm, p less than 0.005). McDonald and Shirodkar procedures had similar obstetric outcomes in patients undergoing their first cerclage. The subgroup of patients with prior cerclage surgery showed improved birth weight when the Shirodkar procedure was performed instead of the McDonald cerclage (mean birth weight 3020 vs 2470 gm, p less than 0.005). An increased rate of primary cesarean section was found in the Shirodkar group (31% vs 17%, p less than 0.005). Complication rates and pregnancy outcome appear to reflect cervical dilatation more than gestational age at time of surgery. PMID- 1892181 TI - Use of hydroxyurea in chronic myeloid leukemia during pregnancy: a case report. AB - The concomitant occurrence of pregnancy and chronic myeloid leukemia is uncommon. The use of hydroxyurea in chronic myeloid leukemia during pregnancy is unknown. We report on a patient with chronic myeloid leukemia in whom hydroxyurea was used during pregnancy with a successful outcome for both mother and fetus. PMID- 1892182 TI - Fetal breathing movements before oxytocin induction in prolonged pregnancies. AB - Fetal breathing movements were recorded before elective labor induction in 65 patients with uncomplicated prolonged pregnancies. Breathing activity was observed in 41 patients and was absent in 24. Comparison of these two groups indicated that the induction period was significantly shorter and the oxytocin requirement significantly lower in the group with no fetal breathing movements (mean, 319.3 vs 648.5 minutes and 1133.7 vs 2708.4 mIU, respectively). These findings remained valid regardless of Bishop scores. The data suggest that fetal breathing movements are predictive of the effectiveness of oxytocin induction in prolonged pregnancies. PMID- 1892183 TI - Study of 156 cases of polyhydramnios and congenital malformations in a series of 118,265 consecutive births. AB - Polyhydramnios associated with congenital anomalies was studied over nine years in 118,265 consecutive pregnancies. The prevalence of this association was 1.32% (156 cases). A case-control study allowed the examination of genetic and environmental factors for the origin of polyhydramnios associated with congenital malformations. Diagnosis of polyhydramnios associated with congenital malformations was performed prenatally in 41% of the cases; 16% of the infants were stillborn. Fifty-five percent of the cases had more than one malformation, 13.4% of them had a chromosomal aberration, and 32% had multiple malformations that do not constitute a syndrome. There was an increase of consanguinity in the parents of our patients. The incidence of polyhydramnios and congenital anomalies in first-degree relatives was 3.8%, and first-degree relatives had more malformations than the controls had (8.3% vs 3.2%). Our study demonstrated the low capacity of a general prenatal screening program because the diagnosis of malformations associated with polyhydramnios was made in only 41% of the cases and only six of 21 chromosomal abnormalities were diagnosed prenatally. We recommend the use of fetal chromosome analysis and careful ultrasonographic examination in every pregnancy complicated by polyhydramnios. PMID- 1892184 TI - Single and multiple administration of a new triphasic oral contraceptive to women: pharmacokinetics of ethinyl estradiol and free and total testosterone levels in serum. AB - Ethinyl estradiol is part of almost every combined oral contraceptive, and its pharmacokinetic characteristics have been thoroughly investigated in numerous studies. However, little is known about its pharmacokinetics during long-term administration, as compared with single-dose administration. In this study 10 women received a triphasic formulation that contained ethinyl estradiol together with the progestin gestodene over one treatment cycle. Mean area under the curve values of ethinyl estradiol were significantly higher on the last treatment day, as compared with the corresponding values obtained from the same women after single-dose administration. However, the observed increase in area under the curve was within the range of pharmacokinetic accumulation, to be expected on the basis of dosing interval and terminal half-life. Another point of interest was the effect of the triphasic preparation on testosterone concentrations in serum. Both total and free testosterone levels were suppressed by about 60% as compared with pretreatment values, and there was no correlation with corresponding sex hormone-binding globulin levels in the serum. PMID- 1892185 TI - Oral tocolysis with magnesium chloride: a randomized controlled prospective clinical trial. AB - A prospective randomized clinical trial was conducted to assess the efficacy and safety of enteric-coated magnesium chloride (SLOW MAG) as an oral tocolytic agent. Seventy-five patients between 24 and 34 weeks' gestation who were treated with intravenous magnesium sulfate for a first episode of preterm labor were enrolled. After a 12-hour contraction-free period on intravenous therapy, patients were randomized by sealed envelope to one of three groups: group 1, SLOW MAG (535 mg every 4 hours); group 2, oral ritodrine (20 mg every 4 hours); or group 3, no therapy (control). Patients receiving oral therapy were treated until delivery or completion of 36 weeks' gestation. No difference was found between groups with respect to time gained with the use of oral therapy or number completing 36 weeks' gestation. Therapy with enteric-coated magnesium chloride was associated with significantly fewer side effects (20%) as compared with ritodrine (48%) (p less than 0.01). Our results suggest that compared with ritodrine, enteric-coated magnesium chloride is as effective in prolonging pregnancy and preventing recurrent preterm labor. However, neither enteric-coated magnesium chloride nor ritodrine appeared to be any more effective in the prevention of preterm delivery than observation alone. PMID- 1892186 TI - The effects of betamethasone on maternal cellular resistance to infection. AB - Antenatal administration of glucocorticoids is often used to facilitate fetal lung maturation in cases of prematurity; however, the effects of betamethasone on maternal immune function have not been established. Therefore maternal immune function was assessed with the use of in vitro techniques. Transient and incomplete suppression of the proliferative response to the T-cell mitogen phytohemagglutinin was demonstrated as early as 24 hours after administration of betamethasone. The magnitude and duration of suppression showed a corresponding increase with advancing gestational age, but these effects were not cumulative and were always short-lived (less than 72 hours). No such suppression of the B cell mitogen lipopolysaccharide was detected. The nonspecific cellular resistance to infection of maternal monocytes was determined through coincubation with the facultative intracellular pathogen Listeria monocytogenes. Increased phagocytic activity with a normal bactericidal effect was measured in the cell preparations obtained from recipients versus nonrecipients of betamethasone. Taken together, these findings clearly show that both specific and nonspecific immune function are intact in the preterm gravid woman after administration of betamethasone and should allay concerns over its use for reasons of infection control alone. PMID- 1892187 TI - Vasopressin and operative hysteroscopy in the management of delayed postabortion and postpartum bleeding. AB - Two women, one with refractory postabortion hemorrhage and the other with refractory postpartum hemorrhage, were managed with vasopressin, operative hysteroscopy, and a dilute vasopressin pack. Both patients had been treated by standard methods (i.e., dilation and curettage) and both were being prepared for a surgical intervention procedure. It was decided in both cases to try to slow the bleeding by injection of vasopressin paracervically and then performance of operative hysteroscopy. In both cases, the injection of dilute vasopressin paracervically when coupled with operative hysteroscopy was quite effective in determining the cause of the bleeding and was instrumental in avoiding major operative procedures. PMID- 1892188 TI - Computerized analysis of episodic changes in fetal heart rate variation in early labor. AB - Fetal heart rate variation in early labor was measured by computerized analysis in cyclic episodes of low or high variation in 136 women at 37 to 42 weeks' gestation. The amplitude (mean +/- SE) in episodes of low variation was 20.6 +/- 0.4 milliseconds; in high variation it was 57.3 +/- 1.1 milliseconds. The duration (mean +/- SE) of low episodes (24.3 +/- 1.3 minutes) was less than that of high episodes (45.1 +/- 2.7 minutes) but was sometimes greater than 1 hour. In episodes of low variation the amplitude was less than 5 beats/min long term in 11% and less than 2.5 milliseconds (pulse intervals) short term in 8%; these measures would be predictive of intrauterine death if persistent before birth. We conclude that the use of decreased fetal heart rate variation as a diagnostic sign of acute fetal hypoxemia in labor is incorrect, because changes of this size occur randomly as a consequence of fetal sleep states. There was no significant correlation between fetal heart rate variation over the last hour of labor and umbilical arterial base deficit on delivery. PMID- 1892189 TI - Ultrasonographic diagnosis of symptomatic deep venous thrombosis in pregnancy. AB - Color flow imaging combined with compression ultrasonography were used to prospectively evaluate symptomatic patients first seen with suspected deep vein thrombosis during pregnancy. The incidence of symptomatic deep vein thrombosis (7 of 10,000 deliveries) shown prospectively by ultrasonography was similar to that of historic controls who had a diagnosis confirmed by venography (11 of 26,191 deliveries). A preferential pattern of proximal left-sided iliac or femoral vein involvement was common to both cohorts, being seen in five of the seven cases diagnosed by ultrasonography and eight of the eleven cases diagnosed by venography. We conclude that ultrasonography, consisting of compression ultrasonography and color flow imaging, can replace venography in the diagnosis and evaluation of the extent of symptomatic deep vein thrombosis during pregnancy. PMID- 1892190 TI - Antimicrobial therapy in preterm premature rupture of membranes: results of a prospective, double-blind, placebo-controlled trial of erythromycin. AB - This study was conducted to evaluate the effectiveness of oral erythromycin treatment in safely prolonging pregnancy among women experiencing preterm premature rupture of membranes. Sixty-five women were randomly assigned to receive double-blind treatment with either erythromycin base or an identical appearing placebo three times daily for 7 days. Only women between 23 and 34 completed weeks' gestation who did not have an indication for delivery were enrolled in the study. Pretreatment microbiologic tests were obtained and women were followed expectantly. Fifty-five women and their newborns completed the protocol and were fully evaluated. Overall, time from rupture of membranes to onset of labor and to delivery was longer, although not significantly, for erythromycin-treated women. Similarly, there was a trend for reduced neonatal intensive care (level II, p = 0.07). When gestational age at enrollment was controlled, erythromycin treatment of women between 28 to 32 weeks' gestation was associated with a prolonged interval from enrollment to delivery [erythromycin: 292 hours (5 to 679); placebo: 54 (12 to 323); p less than 0.044]. Fifty percent of erythromycin-treated women between 28 to 32 weeks' gestation continued their pregnancies at least 13 days after premature rupture of membranes, whereas 50% of placebo-treated women were delivered of infants within 4 days (p = 0.02). Erythromycin treatment among women less than 28 and between 33 to 34 weeks' gestation was not associated with prolonged latency or other changes. There were no differences between erythromycin- and placebo-treated women in the occurrence of clinically recognized chorioamnionitis, postpartum endometritis, or neonatal infectious morbidity. In this double-blind, placebo-controlled trial, erythromycin treatment was well tolerated, safe, and associated with prolongation of pregnancy and reduced intensive neonatal care requirements for selected mother newborn pairs with preterm premature rupture of membranes. PMID- 1892191 TI - Simultaneous measurements of prostacyclin and thromboxane metabolites during the menstrual cycle. AB - The balance between prostacyclin and thromboxane is known to be important for reproductive and cardiovascular health but has been difficult to quantify. Whereas their stable urinary metabolites, 6-keto-prostaglandin F1 alpha and thromboxane B2, may reflect in part systemic changes, it has been suggested that 2,3-dinor-6-keto-prostaglandin F1 alpha and 11-dehydro-thromboxane B2 more adequately reflect systemic production. Therefore we report for the first time the simultaneous measurements of 6-keto-prostaglandin F1 alpha, thromboxane B2, 2,3-dinor-6-keto-prostaglandin F1 alpha, and 11-dehydro-thromboxane B2 during the menstrual cycle. Timed urine collections were obtained from 18 ovulatory women, aged 22 to 40, during the midfollicular and midluteal phases. Serum estradiol, progesterone, urinary pregnanediol glucuronide, estrone glucuronide, and creatinine also were measured. Prostanoid extraction from urine by C18 and silica Bond Elut columns were then separated by high-performance liquid chromatography before radioimmunoassay. Concentrations of all urinary prostanoids were not significantly different in the follicular phase when compared with the luteal phase. A positive correlation of borderline significance was noted between luteal thromboxane B2 and pregnanediol glucuronide (r = 0.70) and between luteal estrone glucuronide and 2,3-dinor-6-keto-prostaglandin F1 alpha (r = 0.68). A significant correlation was found between follicular estrone glucuronide and the 6-keto prostaglandin F1 alpha/11-dehydro-thromboxane B2 ratio (r = 0.83, p less than 0.04). These novel normative data suggest an influence of sex steroids on prostacyclin and thromboxane metabolism. PMID- 1892193 TI - Funic reduction for the management of umbilical cord prolapse. AB - The current management of umbilical cord prolapse centers on attempts to alleviate the pressure of the presenting part on the cord while preparation for cesarean section is being made. A 10-year experience in which there were vigorous attempts to accomplish safe vaginal delivery after the diagnosis of umbilical cord prolapse is presented. Eight cases of umbilical cord prolapse occurred, a frequency of 1 in 277 deliveries (0.37%), all of which had a normal immediate neonatal outcome. Vaginal delivery was accomplished in seven patients (87.5%); diagnosis was made in two of them when delivery was imminent. Five patients were more remote from delivery and had successful funic reduction (manual replacement of the prolapsed cord). Funic reduction is proposed as a potentially beneficial initial step in the management of umbilical cord prolapse. PMID- 1892192 TI - Recurrent mild abruptio placentae occurring immediately after repeated electroconvulsive therapy in pregnancy. AB - We present a case in which electroconvulsive therapy was performed repeatedly in pregnancy because of severe depression with psychotic features and failure of chemical treatment. Each electroconvulsive treatment was immediately followed by uterine contractions and active uterine bleeding, possibly representing recurrent abruptio placentae occurring in association with the treatment. Transient acute episodes of maternal hypertension between 180/90 and 190/100 mm Hg, documented within minutes after application of each electroconvulsive treatment, might explain the abruptio placentae manifested by active uterine bleeding and uterine hyperstimulation. PMID- 1892194 TI - Adverse psychologic consequences of positive cytologic cervical screening. AB - Cervical cancer is still widely prevalent in the female population. This study explores the relationship of cervical cancer screening, positive versus negative Papanicolaou's test results, and psychologic status among lower-income minority women. All patients were interviewed 3 months after they had received initial test results. One hundred six women with normal Papanicolaou's test results were compared with 118 women who were referred for colposcopic examination for follow up of positive test results. Women with positive Papanicolaou's-test results showed statistically significant elevations in worries about cancer and impairments in mood, daily activities, sexual interest, and sleep patterns. More fine-grained analyses revealed that the effects of positive results were most pronounced among those women who did not comply with colposcopy (n = 53). These findings suggest that lack of compliance with follow-up may maintain high levels of uncertainty about disease and may interfere with successful psychologic adaptation. Health education targeted to psychologically vulnerable individuals may reduce psychologic distress and enhance compliance. PMID- 1892195 TI - Fetal atrioventricular and outflow tract flow velocity waveforms during normal second half of pregnancy. AB - Maximum flow velocity waveforms at atrioventricular and outflow tract level were studied longitudinally in 40 fetuses from 18 to 38 weeks' gestation at 3- to 4 week intervals. Flow velocity parameters studied were peak systolic and time averaged velocity and acceleration time at outflow tract level and time-averaged velocity, peak E-wave and peak A-wave velocities, and E/A ratio at atrioventricular level. An increase of all flow parameters with advancing gestational age was found. Aortic parameters were higher than pulmonary ones. Time-averaged, peak E-wave, and peak A-wave velocities were higher at tricuspid level than at mitral level, whereas E/A ratios were higher at mitral level. Outflow tract parameters showed no correlation with period time. A positive correlation for peak E-wave velocity and E/A ratio, and a negative correlation for time-averaged and peak A-wave velocity was found with period time. These results suggest that the normal second half of pregnancy is characterized by rising ventricular stroke volume and output and reduction in ventricular afterload. The left ventricular afterload seems to be lower than the right ventricular afterload. Atrioventricular flow velocities are heart rate dependent. PMID- 1892196 TI - Effect of cigarette smoking on maternal airway function during pregnancy. AB - The effects of cigarette smoking on maternal airway function during pregnancy were investigated in a cross-sectional study of 97 smokers and 175 nonsmokers at different gestational ages. The groups were comparable in age, height, and weight. All subjects were healthy. Forced vital capacity, forced expiratory volume in 1 second, their ratio, the forced expiratory flow rates between 0.2 and 1.2 L, 25% and 75%, and 75% and 85%, and instantaneous flows at lung volumes of 25%, 50%, and 75% were measured. All spirometric tests were unaffected by gestational age. However, all parameters of spirometry were significantly less in smokers than in nonsmokers when cumulative data during pregnancy were compared. Forced vital capacity, forced expiratory volume in 1 second, and their ratio were minimally reduced (4%, p less than 0.05; 8%, p less than 0.001; and 4%, p less than 0.001; respectively) in smokers as compared with nonsmokers. Larger reductions were noted in forced expiratory flow rates between 0.2 and 1.2 L (14%, p less than 0.001) and between 25% and 75% (16%, p less than 0.001), and in instantaneous maximum flows at lung volumes of 75% (11%, p less than 0.001) and 50% (13%, p less than 0.001). Maximum reduction of forced expiratory flow rates between 75% and 85% (26%, p less than 0.001) and in instantaneous flows at maximum lung volumes of 25% (23%, p less than 0.001) suggests marked increases in small-airway resistance and early small-airway disease in smokers. The progression of small-airway disease is related to the level of cigarette exposure. The results of our study demonstrate that the bronchodilatory effect expected in pregnancy is not sufficient to overcome the deleterious effects of cigarette smoking. PMID- 1892197 TI - Effectiveness of antibiotic prophylaxis in preventing bacteriuria after multichannel urodynamic investigations: a blind, randomized study in 124 female patients. AB - One hundred twenty-four women with chronic, persistent lower urinary tract symptoms who had been scheduled for elective urodynamic investigations at Mount Sinai's Urodynamic Investigative Unit were divided into two blind, randomized groups, receiving either a placebo or prophylactic antibiotic. At the time of urodynamic testing, the rate of unsuspected urinary tract infection was 8.1%. There was no statistically significant decrease in postinstrumentation infection rate in the group who received prophylactic antibiotics. We conclude that, given in the fashion described in the study, prophylactic antibiotics are not effective in preventing urinary tract infections caused by urodynamic testing. PMID- 1892198 TI - Transvaginal fetal echocardiography in early pregnancy: normative data. AB - Fifty-two transvaginal ultrasonographic examinations were performed between 10.0 and 14.9 weeks' gestation for the purpose of documenting normal fetal cardiac anatomy. All standard cardiac projections could be obtained by gestational week 12, and many were imaged by week 11. The four-chamber view was visualized in 90% of fetuses at 12 weeks' gestation and in 100% of fetuses examined at 13 weeks. The aortic root in short axis projection and the left ventricle in long axis view could be imaged in 70% and 40% of fetuses, respectively, by 12 weeks' gestation. Aortic and pulmonary valves were first visualized at 12 weeks, as were five chamber, ductus arteriosus, and aortic arch views. The mitral and tricuspid valves were resolved in 60% of fetuses by 11 weeks' gestation. This study of normal cardiac anatomy suggests that there may be significant potential for the diagnosis of many fetal cardiac anomalies during the late first and early second trimesters of pregnancy. PMID- 1892199 TI - Hemostatic wrapping of ruptured liver in two postpartum patients. AB - A variety of surgical techniques with variable success rates have been reported in the management of the spontaneously ruptured liver in pregnancy. We managed two cases of postpartum ruptured liver by wrapping the liver in hemostatic material. Hemostatic encapsulation effectively controlled massive bleeding of ruptured livers in two postpartum patients. PMID- 1892200 TI - Increased inducibility of inflammatory mediators from peripheral blood mononuclear cells of women with salpingitis. AB - To investigate whether immune system activation may contribute to the tissue damage observed in salpingitis, we isolated peripheral blood mononuclear cells and quantitated production of the monocyte activation products tumor necrosis factor-alpha, interleukin-1, and interleukin-6. Unstimulated cells from 7 of 20 women with salpingitis spontaneously released tumor necrosis factor at a concentration greater than 2 SD above the mean value produced by cells from 29 healthy donors. Interferon gamma (200 U/ml) further induced production of tumor necrosis factor from mononuclear cells of 11 women with salpingitis. In contrast, production of tumor necrosis factor by each of 23 other patients who lacked laparoscopic or clinical evidence of salpingitis was similar to that of the controls. In a subset of women whose cells were tested for production of other monokines, three of nine women with salpingitis spontaneously released interleukin-1 but none of the others did so. Four of nine patients with salpingitis also produced interleukin-6, but none of the others did so. None of the monokines were detected in serum from any subject. The results suggest that monocytes from women with salpingitis are primed in vivo and produce inflammatory mediators under conditions where monocytes from other women are poorly responsive. This increased monokine inducibility may contribute to the tubal damage that is the hallmark of salpingitis. PMID- 1892201 TI - Maternal plasma level of endothelin is increased in preeclampsia. AB - Endothelin is a potent vasoconstrictor that is reportedly increased in conditions characterized by endothelial damage. Maternal plasma endothelin levels were compared between 27 women with preeclampsia (23 without and 4 with the hemolysis, elevated liver enzymes, and low platelet count syndrome) and 14 women with normotensive pregnancies. The mean +/- SEM plasma endothelin values were significantly higher in patients with preeclampsia uncomplicated by the hemolysis, elevated liver enzymes, and low platelet count syndrome (5.48 +/- 0.30 fmol/ml vs 3.86 +/- 0.28, p less than 0.001). In addition, the preeclamptic group with the hemolysis, elevated liver enzymes, and low platelet count syndrome had significantly higher endothelin levels than those without the syndrome (8.30 +/- 1.62 fmol/ml vs 5.48 +/- 0.30, p less than 0.05). There was no correlation between plasma endothelin values and either systolic or diastolic blood pressure. We conclude that plasma endothelin levels are significantly increased in women with preeclampsia and particularly in those with the hemolysis, elevated liver enzymes, and low platelet count syndrome, suggesting an association with widespread endothelial damage. PMID- 1892202 TI - In utero fetal muscle biopsy for the diagnosis of Duchenne muscular dystrophy. AB - Deoxyribonucleic acid techniques can be used to diagnose Duchenne muscular dystrophy prenatally in male fetuses that are at risk. Deoxyribonucleic acid based prenatal diagnosis can be impossible when there is only one prior affected male and there is no identifiable deletion or alteration. We performed fetal muscle biopsy in utero in such a case and documented the presence of dystrophin, thereby confirming normality in a male fetus at risk. This first in utero experience adds fetal muscle biopsy to the available procedures for fetal tissue diagnosis. PMID- 1892203 TI - Concentration of digoxin-like immunoreactive substance in patients with preeclampsia and its relation to severity of pregnancy-induced hypertension. AB - Digoxin-like immunoreactive substance (endoxin) was measured in pregnant patients with pregnancy-induced hypertension. The mean level was significantly higher than that in healthy control subjects (p less than 0.001). Patients with eclampsia had a significantly higher concentration than did women with preeclampsia (p less than 0.03). A positive significant correlation was found between concentration of digoxin-like immunoreactive substance and the value of the index of gestosis of von Goecke and Schwabe (p less than 0.03). Analysis of patterns during various kinds of therapy revealed that nitrendipine was most effective in lowering endoxin concentration. Although an insignificant correlation was found between maternal concentration and both birth and placental weights, the compartmental differences observed seem to suggest fetoplacental origin of this substance. PMID- 1892204 TI - A new proline aminopeptidase assay for diagnosis of bacterial vaginosis. AB - Bacterial vaginosis is one of the most common occurring vaginal conditions among women of reproductive age. A rapid and reliable laboratory test for diagnosis of bacterial vaginosis would be helpful in the clinical detection of this disease. Elevated proline aminopeptidase activity has been identified as a reliable marker enzyme for bacterial vaginosis. A proline aminopeptidase assay has been shown to predict accurately women with a clinical diagnosis of bacterial vaginosis. However, this assay has significant practical disadvantages, the most notable of which is the production of a carcinogenic end product, alpha-naphthylamine. We have developed a modified assay for this bacterial vaginosis marker enzyme with L proline p-nitroanilide, a substrate that does not yield a carcinogenic end product. The new proline aminopeptidase assay is a one-step test that is analyzed colorimetrically with microsomal leucine aminopeptidase used as a standard enzyme (linear from 3 to 125 mU per well). We have determined the activity of proline aminopeptidase in vaginal wet preparations from 57 patients with both assay methods. In addition, vaginal smears were examined with Gram's stain and analyzed for bacterial vaginosis with the Spiegel method. When compared with the Spiegel method, the two proline aminopeptidase assay methods were similar with respect to assay sensitivity (93%), specificity (91% to 93%), and the predictive value of a positive result (78% to 82%) or a negative result (97% to 98%). Vaginal wash samples also were assessed for proline aminopeptidase activity. Values for samples identified as bacterial vaginosis positive were significantly different (p less than 0.0001) from those that were negative according to the Spiegel analysis of Gram's stain: negative results, 66 +/- 41 mU/ml; positive results, 704 +/- 145 mU/ml. These findings indicate that this improved proline aminopeptidase assay will offer a rapid, sensitive, and objective laboratory method for the diagnosis of bacterial vaginosis. PMID- 1892205 TI - Pemphigus gestationis (herpes gestationis): a case report. AB - Pemphigus gestationis is a rare disease, probably of immunologic origin, that causes the placenta to absorb immunoglobulins and deposit them in its basement membrane. The resulting placental insufficiency leads to increased morbidity and mortality among the offspring of such patients. A case of pemphigus gestationis is presented, and the importance of early diagnosis is discussed. PMID- 1892206 TI - Inhibin subunits in human placenta: localization and messenger ribonucleic acid levels during pregnancy. AB - This study describes the difference in distribution and levels of inhibin alpha, beta A- and beta B-subunit messenger ribonucleic acids in human placenta during pregnancy. Northern blot analysis indicated that inhibin alpha messenger ribonucleic acid is present in placental extracts collected at the early stage of gestation. Hybridization to inhibin beta A messenger ribonucleic acid was detected in the first trimester but in much lower levels. However, the intensity of the hybridization signal for inhibin alpha- and beta A-subunit messenger ribonucleic acids was greater in extracts prepared from term placentas than in those from the first or second trimester of pregnancy. Low levels of inhibin beta B-subunit messenger ribonucleic acid were observed only in extracts prepared from term placenta. At both early stage and term gestation trophoblast cells showed a positive fluorescent signal with the inhibin alpha-, beta A- and beta B-subunit specific antisera. However, whereas inhibin alpha-subunit was localized in the cytotrophoblast, inhibin beta B-subunit immunoreactivity was observed in the syncytial layer of the villi, and inhibin beta A-subunit was widely distributed. The different distribution of immunoreactive inhibin subunits was confirmed by in situ hybridization, showing the different localizations of the inhibin messenger ribonucleic acids. These results showed that (1) human placenta produces the inhibin alpha- and beta A-subunits as early as the first trimester of pregnancy, (2) messenger ribonucleic acid levels for each of the three inhibin subunits are highest at term, and (3) immunoreactive inhibin subunits are localized differently in placental villi. PMID- 1892207 TI - Circadian rhythms of heart rate and mean arterial pressure in chronically instrumented pregnant rats. AB - With the use of a chronic preparation to directly monitor blood pressure and heart rate in pregnant rats, continuous data were obtained over the last half of gestation in normotensive rats. Over this time span, the animals showed significant decreases in blood pressure and increases in heart rate. Heart rate exhibited marked and consistent circadian rhythmicity with peaks occurring near the midportion of the dark phase of the 24-hour cycle. Blood pressure rhythms were less prominent and peaked later. The trends observed in blood pressure and heart rate over gestation suggest that the pregnant rat is a useful model for studying the cardiovascular effects of pregnancy. PMID- 1892208 TI - The effect of interleukin-1 on adhesion formation in the rat. AB - The potential role of interleukin-1 in postoperative adhesion formation was examined. Cecal abrasion gave a consistently higher adhesion score when compared with sham laparotomy, on the basis of adhesion number, density, and vascularity, and so was chosen for use in further studies. The extent of serosal bleeding during cecal abrasion did not affect adhesion scores. Intraperitoneal injection of 10 micrograms murine recombinant interleukin-1 alpha in cecally abraded animals on the day of surgery and on the following 4 days resulted in a significant increase in adhesion scores when compared with those of cecally abraded animals injected with vehicle alone. Adhesions enhanced with murine recombinant interleukin-1 alpha, which were thicker and more vascular, were equivalently enhanced at doses from 10 to 10,000 ng, implying maximal response over that range. Rats not operated on and receiving recombinant interleukin-1 alpha 2 weeks after injury had increased adhesion formation. These results demonstrate that interleukin-1 alpha may be an important short-term mediator of postsurgical adhesion formation. PMID- 1892209 TI - Acute fetal ductal occlusion in lambs. AB - To assess fetal right ventricular and hemodynamic responses to acute occlusion of the ductus arteriosus, the pulmonary pressure, right and left ventricular output, and right ventricular dimensions of five fetal lambs were measured with simultaneous echocardiographic monitoring. Ductal occlusion resulted in a rise in pulmonary arterial pressure, a decrease in right ventricular output of 68%, an increase in left ventricular output of 18%, and a fall in combined cardiac output of 34%. The right ventricular systolic dimension increased, and the shortening fraction decreased from 0.41 to 0.14. Tricuspid regurgitation started within two heartbeats after ductal occlusion and resolved as soon as the occlusion was released. Acute fetal ductal occlusion imposes a marked increase in the right ventricular afterload, resulting in reversible triscuspid regurgitation. PMID- 1892211 TI - Laparoelytrotomy: abdominal delivery without uterine incision. PMID- 1892210 TI - Prognostic value of CA 125 and neopterin in women with ovarian cancer undergoing second-look laparotomy. PMID- 1892212 TI - Is opposition to abortion unethical? PMID- 1892213 TI - Examination of placentas by pathologists. PMID- 1892214 TI - Maternal genital herpes and gender of offspring. PMID- 1892215 TI - Immunohistochemical expression of P400 protein in Purkinje cells of sphingomyelinosis mouse. AB - Immunohistochemical expression of P400 protein, a glycoprotein localized to the Purkinje cell membrane, has been studied in the cerebellum of spm mouse using anti-P400 monoclonal antibody. The initial change observed in the Purkinje cells was a swelling of the cell body with distortion of the neurites; this occurred as early as 5 weeks of age. A significant, patchy loss of Purkinje cells started at 6 weeks before cerebellar signs became manifest. With progression of the disease the dendritic processes in the molecular layer showed a marked swelling, followed by irregular arborization and finally by disintegration. A few, heterotopic Purkinje cells were found in the subcortical white matter; this was interpreted as an indication that a disturbance in neuronal migration could be superimposed on the sphingolipid metabolic disorder. Additionally, P400-immunoreactive nerve cells were occasionally encountered in areas of the deep cerebellar nuclei and in the lateral vestibular nuclei of the pontine tegmentum. The number of P400 immunoreactive Purkinje cells correlated well with the percentages of the remaining Purkinje cells during the ages of 4 to 7 wks. At the late stage of 10 to 12 weeks almost all Purkinje cells had lost their P400-immunoreactivity. It is suggested that Purkinje cells that fail to express P400 protein may undergo an immunohistochemical degeneration of the plasma membrane. PMID- 1892216 TI - Ontogenetic development of isonicotinehydrazide-induced seizures in rats. AB - Motor seizures elicited by isonicotinehydrazide (INH) were studied in 188 male albino rats aged from 5 days to adulthood. INH was found to be able to induce both minimal, predominantly clonic, and major, i.e. generalized, tonic-clonic seizures during the whole course of development. Tonic hindlimb extension was observed as a part of major seizures even in the youngest group studied. Fifty percent convulsant doses counted in 7-, 12-, 18-, 25- and 90-day-old rats did not significantly differ. The developmental changes found were a poor time resolution of minimal and major seizures during the first two postnatal weeks and significantly longer latency of major seizures in 5- and 7-day-old rat pups in comparison with all other age groups. The importance of the developmental stage of a generator of seizures as well as of the maturation of triggering mechanisms was demonstrated comparing the present results with our previous data. PMID- 1892217 TI - Bilateral porencephalic defect in a newborn after injection of benzol during pregnancy. AB - Porencephaly is usually considered to be a prenatal brain lesion due to a circulatory failure. We report a case of bilateral porencephaly with heterotopia and absence of the septum pellucidum in a newborn. The mother had received several injections of benzol during pregnancy with an intent of inducing abortion. The possibility of a causal relationship between the administration of benzol and the occurrence of the defect is supported by the existence of previously reported cases of cerebral malformations following maternal exposure to organic solvents. PMID- 1892219 TI - Hypocalcemic focal seizures in a one-month-old infant of a mother with a low circulating level of vitamin D. AB - We present a case of a one-month-old infant with hypocalcemia and rickets, with symptoms of focal seizures. The ictal EEG showed left occipital spikes spreading over all of the left hemisphere. From the laboratory studies, we concluded that a low maternal circulating level of vitamin D would cause infantile hypocalcemia and rickets, while immature renal response to parathyroid hormone and transient hypoparathyroidism in infancy would induce hyperphosphatemia. Hypocalcemia may be an important factor in the cause of focal seizures which start even after the age of one month. Further, investigation of maternal vitamin D levels should be done in infantile hypocalcemia. PMID- 1892218 TI - MR imaging of birth brachial palsy in a two-month-old infant. AB - A female baby at two months old was diagnosed as having birth branchial palsy and was studied by magnetic resonance imaging (MRI) which is a non-invasive and safe method for assessing any brachial plexus injury in the infant. A traumatic meningocele involving a root avulsion injury was clearly demonstrated by the MRI findings. PMID- 1892220 TI - Dystrophin in control and mdx retina. AB - To determine whether or not dystrophin really exists in the outer plexiform layer (OPL) of the retina, we studied control and mdx mice, using four kinds of polyclonal antibodies (DMDP-II, 60 kd, 30 kd and DMDP-IV) against dystrophin. Although control OPL showed a positive immunohistochemical reaction with all four antibodies, mdx OPL showed a positive reaction with DMDP-II and DMDP-IV, a negative reaction with 60 kd and 30 kd antibodies. Immunoblot analysis showed the positive band compatible with the immunohistochemical reaction. PMID- 1892221 TI - The Rett syndrome and ornithylcarbamoyl transferase deficiency. PMID- 1892222 TI - Adaptive changes in the developing brain during intrauterine stress. AB - Maturation of neurological performance in moderately to severely growth-retarded newborn infants (SGA) can be accelerated by 3 to 4 weeks or more when compared to the development of appropriately grown infants (AGA) of the same gestation. This is particularly the case in multiple pregnancies or pregnancies characterized by maternal hypertension. This clinical finding has been confirmed by neurophysiological studies on the maturation of brainstem auditory evoked responses (BAERs). The possible mechanisms which underly this phenomenon are not yet elucidated. Glucocorticoids, other steroid hormones and catecholamines are elevated in pregnancies with placental dysfunction, and it is known that these substances have multiple actions on neuronal maturation, particularly on mechanisms of release of neurotransmitters. These observations suggest that the acceleration of brain maturation, and lung maturation, in SGA infants reflects an adaptation of the fetus to early extrauterine life. However, if the placental dysfunction progresses, these mechanisms of adaptation will be overwhelmed by severe malnutrition and anoxia which result in cerebral lesions and risk of death. The clinical goal at the present time for obstetric management of these risk pregnancies is to distinguish between these two periods. PMID- 1892223 TI - Vascular alterations in Fukuyama type congenital muscular dystrophy. AB - Blood vessels in muscle biopsy specimens from 6 Fukuyama type congenital muscular dystrophy (FCMD) patients were examined by electron microscopy and compared with ones in non-diagnostic biopsy specimens from age-matched controls and patients with childhood neuromuscular disorders. The most striking feature was the blister like swelling of vascular endothelial cells in the biopsied muscle specimens from 5 of the 6 patients with FCMD. Morphometric analysis of capillaries in biopsied muscles showed the extremely greater capillary, endothelial and pericyte areas in the FCMD patients than in controls. These phenomena are quite similar to those found in Duchenne muscular dystrophy (DMD) at the preclinical stage and suggest an as yet undetermined process in blood vessels in FCMD as well as DMD. An immunohistochemical study involving dystrophin antibodies showed positive staining in FCMD. PMID- 1892224 TI - Prediction of the prognosis in neonatal asphyxia by photo-evoked eyelid microvibration. AB - Neonatal asphyxia causes hypoxic-ischemic encephalopathy and may damage the central nervous system. We studied neonatal asphyxia with photo-evoked eyelid microvibration (PEMV) which is a blink reflex elicited by photic stimuli. The latency of PEMV changed according to the severity of encephalopathy and the degree of unconsciousness. All of the neonate who had showed disappearance of PEMV died. When the prolonged latency persisted, the infant had a strong probability of sustaining neurological sequelae. PEMV provides useful information for predicting the outcome of neonatal asphyxia. PMID- 1892225 TI - Supine and prone head orientation preference in term infants. AB - Head orientation preference in the supine and prone positions was studied in 62 healthy term born infants at three different times within 24 hours after delivery. Head orientation preference was related to: the foetal position, the initial head position when the newborn was lying prone on the abdomen of the mother, the handedness of the parents and the state of the infant (according to Prechtl). Although for the whole group a head orientation preference for the right side was observed, an individual significant head orientation preference was observed in less than 50% of the infants studied. Neither the occurrence nor the direction of head orientation per individual was constant during the observation period. No relationship was found between an infant's head orientation and foetal position, initial head position, handedness of the parents, or the state of the infant. Our data suggest that persistent head orientation preference to one side in a healthy term born infant within 24 hours after delivery is a sign of abnormality. Head orientation to the right should not be considered as a sign of normality. PMID- 1892226 TI - Three modality evoked potentials in Charcot-Marie-Tooth disease (HMSN-1). AB - Sixteen patients with dominant hereditary motor-sensory neuropathy type I (HMSN I), members of 5 families, underwent trimodality evoked potential studies. All patients had clinically normal optic nerves. History of deafness was present in 3 patients and sensory-neural hearing defect was found in 5 of 7 patients in whom audiometry was obtained. In 43.7 percent of the subjects significant prolongation of P100 of the VEP was found. Prolongation of N19 of the SEP was found in all 12 subjects examined. Significant bilateral prolongation of peak I of the ABEP was found in 37.5 percent of the subjects and in 50 percent of the ears examined: these findings indicated that in addition to peripheral nerves, the myelin of the optic and cochlear nerves is also affected in HMSN type I. PMID- 1892227 TI - Liver histopathology in clinical Reye syndrome. AB - Analysis of the liver histopathology in 19 children with clinical Reye syndrome (RS) revealed that nine had diffuse panlobular steatosis, one giant cell hepatitis, one a mild choledochal cyst with inflammation, two multifocal spotty necrosis and one multiple centrilobular necrosis, the other five being normal. Four of the nine patients with diffuse panlobular steatosis showed microvesicular fatty droplets with central nuclei, which was consistent with findings characteristic for typical RS. Two cases showed a periportal area dominant macrovesicular fatty change, which was highly suggestive for metabolic disorder. In the other three cases, the findings were so variable in terms of the size of lipid droplets and the location of nuclei in hepatocytes that it was not possible to provide any clue for defining a diagnosis. These results confirmed the legitimacy of the diagnostic criteria of RS which included a liver biopsy as one of the mandatory conditions. They also indicated that RS-mimicking clinical pictures can be presented by miscellaneous conditions in which liver histology does not necessarily helpful in establishing definite diagnosis. PMID- 1892228 TI - Stevens-Johnson syndrome secondary to ingestion of salmon berries. AB - Stevens-Johnson syndrome is an immune mucocutaneous disorder which can follow viral infections, mycoplasma infections and the ingestion of some drugs. There is also evidence supporting this disease as a hypersensitivity disorder. We observed a four-year-old girl with Stevens-Johnson syndrome attributed to ingestion of salmon berries (Rubus spectabilis). PMID- 1892229 TI - Trauma care in Alaska. PMID- 1892230 TI - Surviving physician stress. A small town view. PMID- 1892231 TI - Humana Hospital-Alaska Air Ambulance: use of multidisciplinary aeromedical teams. PMID- 1892232 TI - Sexually speaking ... taking a sexual history. PMID- 1892233 TI - PIAA breast cancer study: delay in diagnosis expensive. PMID- 1892234 TI - History of medicine in Alaska. George N. Wagnon, M.D. PMID- 1892235 TI - The labrets of the northern "Esquimaux" (1826). PMID- 1892236 TI - Chronic myelogenous leukemia. PMID- 1892237 TI - Thermal effects and histologic changes from Nd:YAG laser irradiation on normal and diseased aortic tissue using a novel angioplasty catheter with a mobile optical fiber: an in vitro assessment. AB - Although various laser angioplasty devices are currently being examined, thermal damage and perforation of the vessel wall remains the major acute complication of vascular laser recanalization. Consequently, the aim of this study was to investigate the thermal effects and histologic changes from laser irradiation (Nd:YAG, 1064 nm) on normal and diseased aortic tissue using a novel angioplasty device. During laser emission the coaxially guided optical fiber tip was positioned in reference to the end hole of the metallic capped probe as follows: (1) at the end hole (metal-cap position), (2) protruding 10 mm from that end hole (bare-fiber position), (3) withdrawn 5 mm into the metal cap's lumen (hot-tip position). In total, 96 laser impacts (25 joule: 5 W, 5 s, each) were produced on normal and atherosclerotic aorta in air through a 0.2-mm-core-diameter silica quartz fiber, with direct contact on the intimal surface of the target tissue by both the fiber and the metal cap and by either the fiber or the metal cap (n = 32 each). Tissue temperature was measured by means of special sensors positioned opposite the irradiated intimal spot in direct contact with the adventitial surface. Morphohistologic evaluation of lesions was performed and injury indexes were determined. PMID- 1892238 TI - Same-day angioplasty and diagnostic catheterization: safe and effective but riskier in unstable angina. AB - Percutaneous transluminal coronary angioplasty was performed at the time of the diagnostic catheterization in 188 patients (215 lesions) at a University Hospital in order to assess the efficacy of this approach and the potential role it should play in the evaluation and treatment of patients. Patients either presented for diagnostic catheterization for evaluation of stable coronary disease (79 patients) or for unstable or new onset anginal symptoms (109 patients). Lesions were graded as to whether they were simple or complex; and post angioplasty films were reviewed for success rate, and degree of revascularization. Patients who were referred for stable anginal symptoms had a slightly higher success rate (91%) compared to those who were referred for new onset or more unstable symptomatology (85%, p = ns). Additionally, lesions morphology was judged to be more complex in unstable patients, as 67% had complex lesions with the presence of thrombus or ulcerated plaque in 56% of these stenoses. Angioplasty success was high for simple lesions in all patients, but was most unfavorable for complex stenoses in patients who presented with unstable symptoms (81% success rate). In patients who presented with new onset or unstable symptoms multivessel disease was present in 69% and angioplasty was more often geared at dilating a culprit stenosis leaving only 49% of these patients with complete revascularization. On the other hand, in 76% of those patients who presented with stable angina complete revascularization was a common outcome. Length of hospital stay was considerably shorter at 2.9 +/- 0.8 days in those patients who presented with stable symptoms.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1892239 TI - The influence of CLS 2210 on the course of myocardial infarction: a pilot study in man. AB - To assess the effect of CLS 2210 (a new formulation of calcium dobesilate) on the evolution of acute myocardial infarction, 100 patients presenting their first infarct were distributed, according to their sequential admissions to the hospital, into CLS 2210-treated group (50 patients) or a comparison group (50 patients not receiving CLS 2210). The two groups were similar in age, sex, predisposing factors, and site of infarction. Intravenous infusion of CLS 2210 was begun within six hours of onset of chest pain and continued for seventy-two hours. Thereafter, it was given, as oral capsules, in a dose of 1,000 mg every eight hours throughout the hospitalization. Before and during the trial, blood samples were drawn for the measurements of serum concentrations of creatine kinase (CK), and twelve-lead electrocardiograms (ECGs) were obtained serially in each patient. All objective data were analyzed on a coded basis without reference to the treatment. In the comparison group, thirty-six to forty-eight hours was required for CK to fall to 50% of the baseline value, whereas in the CLS 2210 treated group it reached 50% of the baseline in eighteen to twenty-four hours. For each infarction site, a statistically significant fall was reached earlier in the CLS 2210 group. CK, the ECG index, and the sum of the ST segments showed earlier and more rapid improvement in the CLS 2210 group than in the comparison group. The consumption of narcotic analgesic agents and nitroglycerin was substantially less in the CLS 2210 group than in the comparison group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1892240 TI - Impedance cardiography for repeated determination of stroke volume in elderly hypertensives: correlation with pulsed Doppler echocardiography. AB - In this double-blind, crossover study the authors have validated stroke volume determination by impedance cardiography against the pulsed Doppler echocardiographic method in elderly hypertensives. They found a good correlation between the stroke volume values obtained by the two methods over a range of values from 30 to 130 mL. The coefficient of linear regression was about .95 at each visit. The mean of the differences was -0.73 mL with a standard deviation of 8.46. Given that individual differences are normally distributed, the values corresponding to 2 standard deviations of the mean define a range covering 95% of the observed differences. From the distribution of the data around the mean plot it appears that, in comparison with pulsed Doppler, impedance cardiography tends to slightly underestimate stroke volumes of greater than 90 mL and to overestimate values of less than 50 mL. The results of this study indicate that impedance cardiography may represent a reliable alternative to pulsed Doppler echocardiography for the noninvasive estimation of cardiac output at rest in elderly patients. PMID- 1892241 TI - Venous gangrene (phlegmasia caerulea dolens) complicating heart failure from severe mitral stenosis--a case history. AB - Gangrene of the left upper limb was found to complicate severe mitral stenosis presenting with heart failure in a sixty-eight-year-old woman with a documented left atrial thrombus. Arterial obstruction as the cause of gangrene was excluded by Doppler-assisted assessment of the peripheral pulses. Venous gangrene can complicate severe mitral stenosis and must be distinguished from arterial embolization, in which urgent surgical treatment is imperative. PMID- 1892242 TI - Striking CT scan findings in a case of unilateral moyamoya disease--a case report. AB - The authors report striking CT scan findings in a young woman with unilateral Moyamoya disease. Serial CT scans showed features that paralleled the clinical and pathophysiologic evolution of the disorder, in much the same way as has been reported in studies using serial angiograms. PMID- 1892243 TI - Coronary artery aneurysms--a case study and literature review. AB - Coronary artery aneurysms are detected with increasing frequency owing to the advent of coronary angiographies. Although most patients with coronary artery aneurysms are asymptomatic, manifestations of myocardial ischemia may occur. The case described herein serves as a basis for a discussion of the pathogenesis, clinical manifestations, detection, and treatment of coronary artery aneurysms. PMID- 1892244 TI - Genetic mapping by single sperm typing. AB - The polymerase chain reaction makes it possible to analyse DNA sequences in a single cell and has led to a new approach for constructing genetic maps. We describe a procedure called 'sperm typing' which can accurately classify individual meiotic products as recombinant of non-recombinant. This permits the linkage relationships among DNA polymorphisms to be determined without pedigree analysis. PMID- 1892245 TI - One-dimensional isoelectric focusing and immunoblotting of bovine major histocompatibility complex (BoLA) class I molecules and correlation with class I serology. AB - One-dimensional isoelectric focusing followed by immunoblotting and development of the immunoblots with the monoclonal antibody HC-10, raised against denatured HLA class I heavy chains, was used to demonstrate biochemical variation in cattle MHC (BoLA) class I molecules. The bands obtained correlated well with BoLA-A specificities. Two or three bands were identified for the specificities w7, w8, w16, w18, w21, cph43 and cph49, whereas no bands were observed for the specificity w2. Two serologically indistinguishable subtypes of specificity w18 were identified. PMID- 1892246 TI - Mouse monoclonal antibodies to bovine blood group antigens: additional results. AB - Seven fusions of mouse myeloma cells with spleen cells from mice immunized with bovine red cells yielded 61 clones producing discriminant antibodies out of total of 651 secreting clones. Although antigenic factors of all known bovine blood group systems were present on the donors' cells, the antibodies identified reacted with antigenic factors from only five systems, A, B, F, S and Z. The antibody specificities produced by more than two clones were anti-A1 or -A2 (21 clones), -S (9),- Z(6),-G' (3) and -V1 (3). The absence of clones secreting antibodies to antigens of the other systems, especially the complex C system, remains unexplained. The properties of the antibodies reacting with antigens of the S system (anti-SU", anti-SUU') and of the B system (O-like antibodies) are in accordance with previous interpretations of polyclonal sera and with present knowledge of the genetic map of the B system. PMID- 1892247 TI - Sheep gene mapping: additional DNA markers included (CASB, CASK, LALBA, IGF-1 and AMH). AB - DNA extracted from 25 hamster-sheep hybrid cell lines was subjected, after Southern blotting, to hybridization with CASB, CASK, LALBA, IGF-1 and AMH cDNA probes. CASB and CASK segregated together and IGF-1 and LALBA were found syntenic with the LDHB-PEPB-TPI-GAPD-SHMT-KRTB group. No other synteny was observed with any of the previously described groups using the same hybrid cell panel. Gene nomenclature: ACO 1: aconitase 1 (soluble); ADA: adenosine deaminase; AMH: antiMullerian hormone; ARA 1: murine sarcoma 3611 viral (v-raf) oncogene homologue 1; CASB: beta-casein; CASK: kappa-casein; ENO 1: enolase 1 (alpha); G6PD: glucose-6-phosphate dehydrogenase; GALA (or GLA): glactosidase (alpha); GAPD: glyceraldehyde -3- phosphate dehydrogenase; GPI: glucose phosphate isomerase; GSR: glutathione reductase; HBG: haemoglobin gamma; HPRT: hypoxanthine phosphoribosyl transferase; IDH 1: isocitrate dehydrogenase 1 (soluble); IGF-1: insulin growth factor 1; ITPA: inosine triphosphatase; KRTA: keratin (acid); KRTB: keratin (basic); LALBA: alpha-lactalbumin; LDHA: lactate dehydrogenase A; LDHB: lactate dehydrogenase B; MDH 2: malate dehydrogenase NAD (soluble); ME 1: malic enzyme (soluble); MPI: mannose phosphate isomerase; NP: nucleoside phosphorylase; OLA: ovine leucocyte antigen; OTC: ornitine carbamoyltransferase; PAIS: phosphoribosyl amino imidazole synthetase; PEPA, PEPB, PEPC: peptidase A, B, C; PGD: phospho gluconate dehydrogenase; PGK: phosphoglycerate kinase; PGM 3: phospho glucomutase 3; PKM 2: pyruvate kinase (muscle); PLP: proteolipid protein; PRGS: phosphoribosyl glycinamide synthetase; RCP: red cone pigment; SHMT: serine hydroxymethyl transferase; SOD 1: superoxide dismutase 1 (soluble); SYN 1: synapsin 1; TPI l: triose phosphate isomerase 1. PMID- 1892248 TI - Two new common alleles of erythrocyte adenosine deaminase (ADA) in pigs. AB - New adenosine deaminase variants ADA C and ADA D were found by means of agarose gel electrophoresis in pig erythrocytes. Family data supported the hypothesis that these are controlled by codominant alleles ADAC and ADAD. The ADAC allele was present in Large White (q = 0.076), Landrace (q = 0.037) and their crosses with other breeds. The ADAD allele was present in Duroc (q = 0.067) and its crosses. Allele frequencies for six pig breeds are given. PMID- 1892250 TI - Mm, a new factor in the porcine M blood group system. AB - By means of a new antiserum, Mm, the Mae phenotype can be shown to be controlled by the Maem allele, the Mef phenotype by either the original Mef or a new Mefm allele, and the Mbe(f) phenotype by the Mbe(f)m allele. The complexity of the porcine M system is now extended to 13 internationally recognized blood group factors controlled by at least 19 alleles. PMID- 1892249 TI - Repeat sequences from complex ds DNA viruses can be used as minisatellite probes for DNA fingerprinting. AB - In a search for new fingerprinting probes for use with sheep, repeat sequences derived from five poxviruses, an iridovirus and a baculovirus were screened against DNA from sheep pedigrees. Probes constructed from portions of the parapox viruses, orf virus and papular stomatitis virus and the baculovirus from the alfalfa looper, Autographa californica, nuclear polyhedrosis virus all gave fingerprint patterns. Probes from three other poxviruses and an iridovirus did not give useful banding patterns. PMID- 1892251 TI - Inheritance of the equine Tf F3 allele. AB - The inheritance of the equine Tf F3 allele was examined in 39 parent-offspring combinations. For 26 of the cases the allele inherited by the offspring from the heterozygous parent could be determined. The proportion of individuals that inherited the F3 variant compared to the alternative allele was exactly 1:1. In five cases the parental phenotype was identical to that of the offspring. For the remaining eight cases the parent was homozygous for the F3 allele and all offspring had the F3 allele. The results were consistent with Mendelian inheritance. PMID- 1892252 TI - Ovine dinucleotide repeat polymorphism at the MAF23 locus. PMID- 1892253 TI - Detection of insertion polymorphisms in 5' flank and second intron of the porcine growth hormone gene. PMID- 1892255 TI - Effect of age on the concentrations of amino acids in the plasma of healthy foals. AB - The concentrations of 23 amino acids in the plasma of 13 healthy foals were determined before suckling, when foals were 1 to 2 days old, 5 to 7 days old, 12 to 14 days old, and 26 to 28 days old. The ratio of the branched chain amino acids to the aromatic amino acids was also calculated at the 5 time points. Analysis of the concentrations at the 5 ages revealed a significant temporal relationship for each amino acid ranging from a polynomial order of 1 to 4 inclusively. There were significant differences between several concentrations of amino acids in plasma at specific sample times; however, no consistent patterns were revealed. The concentrations of amino acids in healthy foals were markedly different from previously determined values in adult horses. The significant differences in the concentrations of amino acids in plasma of healthy foals at the 5 ages may represent developmental aspects of amino acid metabolism or nutrition. PMID- 1892254 TI - Proteoglycan synthesis and content in articular cartilage and cartilage repair tissue in horses. AB - Hexosamine concentration, DNA concentration, and [35S]sulfate incorporation for articular cartilage obtained from various sites in the metacarpophalangeal and carpal joints of horses were measured. The same measurements were made on the repair tissue filling full-thickness articular defects in the intermediate carpal bone and on cartilage surrounding partial-thickness defects 6 weeks after the defects were created arthroscopically. Cellularity (measured as DNA concentration), proteoglycan content (measured as hexosamine concentration), and proteoglycan synthesis (measured as [35S]sulfate incorporation) varied according to the site sampled. Cartilage from the transverse ridge of the head of the third metacarpal bone and the radial facet of the third carpal bone had the lowest hexosamine concentration, whereas rate of proteoglycan synthesis was lowest in cartilage from the transverse ridge of the head of the third metacarpal bone and the distal articular surface of the radial carpal bone. Repair tissue filling a full-thickness cartilage defect at 6 weeks was highly cellular. It was low in proteoglycan content, but was actively synthesizing these macromolecules. In contrast, the cartilage surrounding a partial-thickness defect was unchanged 6 weeks after the original defect was made. PMID- 1892256 TI - Effects of conditioning and maximal incremental exercise on oxygen consumption in sheep. AB - To assess the suitability of sheep for exercise studies, the effect of incremental exercise and conditioning on oxygen consumption (VO2) was studied. Six sheep were adapted to a treadmill and subsequently trained 8 weeks. The sheep were then studied, in random order, using 3 incremental exercise protocols (EX-1, EX-2, and EX-3). The protocols were chosen to approximate high (EX-1), moderate (EX-2), and low (EX-3) intensity exercise by varying treadmill speed and incline. The sheep were then conditioned for an additional 12 weeks and retested on the EX 2 protocol. During exercise, VO2, gas exchange ratio (R), and rectal temperatures (Tb) were recorded. All 3 protocols resulted in significant increases in VO2, R, and Tb (P less than 0.05). Maximum VO2 for EX-1, 49.9 +/- 5.0 ml/min/kg of body weight, was significantly greater than maximum VO2 for EX-2 and EX-3, 37.8 +/- 6.5 and 42.3 +/- 6.0 ml/min/kg, respectively (P less than 0.05), whereas maximum R and maximum Tb were similar. After the additional 12-week conditioning, time on the treadmill increased 40% from 9.58 +/- 0.87 to 13.4 +/- 0.44 minutes, and maximum VO2 increased 27% to 48.1 +/- 9.1 ml/min/kg. These data indicated that maximum VO2 varied with intensity of the exercise, 12 weeks of maximal exercise conditioning was sufficient to produce a measurable training effect (ie, increase endurance and maximum oxygen consumption) and sheep are suitable for maximal exercise studies where VO2 measurements are desired. PMID- 1892257 TI - Influence of type of enclosure on exercise fitness of dogs. AB - The effect of various confinement conditions on physical fitness in dogs was evaluated. Eighteen 9.5- to 10-month-old female purpose-bred Beagles were maintained individually for 3 months at a time in 1 of 6 confinement conditions: Condition A--an outdoor housing area with a conventional dog house and free access to a 6.1 x 9.1-m pen; condition B--outdoor kennel with a conventional dog house and free access to a 1.8 x 6.1-m run; condition C--indoor environmentally controlled 1.2 x 3.66-m run; condition D-0.9 x 1.2 x 0.84-m conventional laboratory cage in an indoor environmentally controlled room; condition E--0.9 x 1.2 x 0.84-m conventional laboratory cage in an indoor environmentally controlled room with treadmill exercise (7 km/h at a 10% grade) for 30 min/d, 5 d/wk; condition F--0.71 x 0.86 x 0.69-m conventional laboratory cage in an indoor environmentally controlled room. During the final week of each 3-month interval, muscle succinate dehydrogenase enzyme activities and submaximal exercise heart rates (during treadmill exercise) were determined to estimate physical fitness. Also, 5 days after being moved into a different housing condition, blood samples were collected for plasma cortisol determination. The type of confinement condition for dogs had little effect on muscle succinate dehydrogenase activity, but had a modest effect on submaximal exercise heart rates of dogs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1892258 TI - Exogenous creatinine clearance as a measure of glomerular filtration rate in dogs with reduced renal mass. AB - Renal mass was surgically reduced in 78 dogs by uninephrectomy or by combined renal infarction and uninephrectomy. Renal clearance of inulin and renal clearance of exogenous creatinine were determined simultaneously, and the creatinine to inulin clearance (C/I) ratio was calculated. Clearance procedures were performed 2 to 3 months after reduction of renal mass, and were repeated at intervals thereafter. Overall, the C/I ratio was 1.008 +/- 0.007 for 192 determinations, with a highly significant correlation (R2 = 0.994, P less than 0.0001) between creatinine clearance and inulin clearance. There was no significant effect of gender of dogs, time after partial renal ablation, or dietary protein intake on C/I ratios. Degree of renal ablation did not affect C/I ratios. The results indicated that exogenous creatinine clearance is a valid measure of glomerular filtration rate in both male and female dogs with reduced renal mass. PMID- 1892259 TI - Bacterial and mycoplasmal flora of the healthy camelid conjunctival sac. AB - Healthy conjunctival sacs of 88 animals of 3 species of captive camelids (Lama glama, Lama guanicoe, Lama pacos) and llama-guanaco hybrids were sampled for bacterial and mycoplasmal flora. Mycoplasmas were not isolated from any animal. Eleven genera of bacteria were isolated. The most frequent isolates were Staphylococcus epidermidis and Pseudomonas spp. Nine varieties of Pseudomonas were found, which represented at least 3 Pseudomonas species. Many of the bacterial isolates (especially the pseudomonads) are potential pathogens in the eyes of these camelids. PMID- 1892260 TI - Characterization of eugonic fermenters group EF-4 by polyacrylamide gel electrophoresis and protein immunoblot analysis. AB - Whole-cell lysates and proteinase K-extracted lipopolysaccharide (LPS) of 19 strains of the group eugonic fermenter-4 (EF-4) were analyzed by electrophoresis and protein immunoblotting. These strains were isolated from dog- and cat-bite abscesses in human beings, ferret and human gastric lesions, and cat-lung infections. These strains represent 2 biovar groupings; EF-4a biovars ferment glucose and possess arginine dihydrolase activity, whereas EF-4b biovars do not. Electrophoresis of whole-cell lysates could distinguish between these biovars groups. Electrophoresis of LPS extracts revealed that all strains of EF-4 possess smooth chemotypes. Two strains of EF-4a reacted weekly in protein immunoblots and revealed distinct LPS profiles. These studies suggests that subgroups of EF-4 biovars may exist. PMID- 1892261 TI - Enzyme-linked immunosorbent assay for the detection of Salmonella enteritidis infection in chickens. AB - An ELISA was developed and tested for its ability to detect antibodies against Salmonella enteritidis in chickens. Various features of the ELISA were evaluated and optimized. The outer membrane protein antigens selected by use of the protein immunoblotting method made the assay specific and sensitive. The assay was evaluated in chickens experimentally infected with S enteritidis. Blood samples collected at weekly intervals after experimental infection with S enteritidis were analyzed by ELISA. Results of the ELISA were compared with those of conventional serum plate and microagglutination tests. The ELISA was more sensitive and specific in the detection of S enteritidis infection than the other 2 conventional tests. PMID- 1892262 TI - Effects of hemolysis and storage on quantification of hormones in blood samples from dogs, cattle, and horses. AB - Veterinary diagnostic endocrinology laboratories frequently receive hemolyzed plasma, serum, or blood samples for hormone analyses. However, except for the previously reported harm done by hemolysis to canine insulin, effects of hemolysis on quantification of other clinically important hormones are unknown. Therefore, these studies were designed to evaluate effects of hemolysis on radioimmunoassay of thyroxine, 3,5,3'-triiodothyronine, progesterone, testosterone, estradiol, cortisol, and insulin in equine, bovine, and canine plasma. In the first experiment, hormones were measured in plasma obtained from hemolyzed blood that had been stored for 18 hours. Blood samples were drawn from pregnant cows, male and diestrous female dogs, and male and pregnant female horses. Each sample was divided into 2 equal portions. One portion was ejected 4 times with a syringe through a 20-gauge (dogs, horses) or 22-gauge (cows) hypodermic needle to induce variable degrees of hemolysis. Two subsamples of the blood were taken before the first and after the first, second, and fourth ejections. One subsample of each pair was stored at 2 to 4 C and the other was stored at 20 to 22 C for 18 to 22 hours before plasma was recovered and stored at -20 C. The second portion of blood from each animal was centrifuged after collection; plasma was recovered and treated similarly as was blood. Concentrations of thyroxine in equine plasma, of 3,5,3'-triiodothyronine, estradiol, and testosterone in equine and canine plasma, and of cortisol in equine plasma were not affected by hemolysis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1892263 TI - Comparison of inhalation-to-perfusion ratio in anesthetized dogs with barrel shaped thorax vs dogs with deep thorax. AB - Interregional, as well as intraregional (local), distributions of the inhalation to-perfusion ratio were analyzed in the lungs of 20 prone anesthetized healthy dogs--10 dogs with barrel-shaped thorax (Beagles) and 10 dogs with deep thorax (Greyhound-type dogs)--using 99mTc inhalation-perfusion lung scintigraphy. Dorsoventral and lateral views were analyzed. In both types of dogs, the ratio between the mean inhalation and perfusion values (interregional mismatching factor gamma) decreased from craniad to caudad and the decrease was more sustained in the right than in the left lung. However, the total decrease was less in Greyhound-type dogs than in Beagles (cranial-to-caudal decrease of 14 and 27%, respectively, in the left lung, and 62 and 56%, respectively, in the right lung). The dorsal-to-ventral distribution of gamma was different in the 2 types of dogs. In Beagles, it increased from dorsal to ventral zones by about 50% of the initial dorsal zone value, whereas in Greyhound-type dogs, only a slight dorsal-to-ventral decrease was evident, with the exception of the more ventral zone. Differences in the intraregional mismatching factor (rho) indicated that the intraregional inhalation-to-perfusion inequalities were more pronounced within the caudal regions and within the ventral zones of the lungs in both types of dogs, and in the more cranial zones in the lungs of Beagles. However, the degree of intraregional mismatching was generally lower in Greyhound-type dogs. Thus, the gravitational force is not the dominating determinant of interregional or intraregional inhalation-to-perfusion ratio distributions in the lungs of anesthetized prone dogs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1892264 TI - Evaluation of carbohydrate malassimilation and intestinal transit time in cats by measurement of breath hydrogen excretion. AB - Techniques for the measurement of breath hydrogen excretion have been evaluated in dogs and the breath hydrogen test has been shown to be useful for clinical diagnosis and as a research tool. A simple method was developed for collection of expired air and measurement of breath hydrogen concentrations in cats, which enabled demonstration of carbohydrate malassimilation. Breath hydrogen concentrations were measured in healthy cats after food was withheld and after xylose and lactulose administration. Breath samples were collected by use of an open flow system with the cat confined in an acrylic plastic chamber. Breath hydrogen excretion did not exceed 0.53 ml of hydrogen/h in cats not fed. Breath hydrogen concentrations after the ingestion of xylose, a pentose sugar given orally at 0.75 g/kg of body weight, were not significantly higher from those of cats not fed. After ingestion of 3.35 g of lactulose, a nonabsorbable disaccharide, breath hydrogen excretion increased and breath hydrogen concentrations were significantly higher by 45 minutes (P less than 0.05) and 60 minutes (P less than 0.01) from breath hydrogen concentrations measured in cats not fed and after xylose administration. Administration of lactulose at an increased dosage resulted in further significant (P less than 0.01) increases in breath hydrogen excretion. In this study, mouth-to-cecum transit times were variable. A mean +/- SEM mouth-to-cecum transit time of 86 +/- 6 minutes was calculated from measurement of breath hydrogen excretion after oral administration of 3.35 g of lactulose.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1892265 TI - N-acetyl-beta-D-glucosaminidase as a predictor of milk loss and recovery after clinical mastitis. AB - Milk samples were collected at onset of 508 episodes of clinical mastitis on a 1,700-cow dairy farm in Michigan. Daily milk production and disease events were recorded for all cows in the herd. Despite statistical association with severity of mastitis, this association was too weak for N-acetyl-beta-D-glucosaminidase (NAGase) activity to be of great value as a prognostic test for clinical mastitis. High milk NAGase activity was significantly (P less than 0.0001) associated with: increased duration of treatment; increased duration of clinical signs of mastitis; decreased daily milk production; and increased risk of the cow being culled because of mastitis. The NAGase value was combined with days in milk production, baseline milk production before mastitis onset, parity, and season of onset to predict the outcome of clinical cases as measured by the first 3 aforementioned variables. Statistical models explained little of the variability among cows in duration of treatment (R2 = 0.11), duration of clinical signs of infection (R2 = 0.11), and milk production change (R2 = 0.09). PMID- 1892266 TI - Celiac trunk cannulation for obtaining abomasal lymph from cattle. AB - Cannulation of the celiac trunk was surgically performed in 26 Holstein steers. The procedure was successful in 23 (88.5%) of the steers. Twenty-two of the steers were infected either naturally or experimentally with the abomasal nematode, Ostertagia ostertagi and/or other gastrointestinal parasites. The remaining 4 steers were not infected. Lymph obtained after surgery was used in various immunologic and biochemical assays. Daily lymph flow rate and total and differential WBC counts were determined after surgery in 4 of the infected and 3 of the noninfected steers. Steers were euthanatized for tissue specimen collection 7 days after surgery. At the time of euthanasia, lymph was still flowing from the cannula of 13 (56.5%) of the steers in which surgery was successful. This surgical procedure represents a valuable technique for studying at the local level, immunologic and physiologic responses of cattle to infection with O ostertagi. PMID- 1892267 TI - Effects of exploratory laparotomy on plasma and peritoneal coagulation/fibrinolysis in horses. AB - Plasma and peritoneal fluid samples were collected before and after surgery from 6 horses undergoing a ventral midline exploratory laparotomy and from 6 anesthetized control horses. Coagulation/fibrinolytic components measured in the plasma and peritoneal fluid of these horses included the functional activity of antithrombin III, alpha-2 antiplasmin, plasminogen, and protein C, and the concentrations of fibrinogen and fibrin degradation products. Peritoneal fluid antithrombin III, fibrin degradation products, and plasminogen values were significantly increased after surgery (over time) in principal horses. Compared with control horses, postoperative peritoneal fluid from horses undergoing laparotomy had significantly increased antithrombin-III activity at 12 and 72 hours, alpha-2 antiplasmin activity at 24 hours, fibrin degradation product concentrations at 6, 12, 24, 72, 96, and 144 hours, plasminogen activity at 6, 12, 24, 48, 72 and 96 hours, and protein-C activity at 12, 24, 72, and 96 hours. There were no significant changes in the peritoneal fibrinogen concentration in principal horses. Plasma plasminogen activity was significantly decreased at 24 hours after surgery in principal horses, compared with controls. Changes were minimal in the remaining plasma coagulation/fibrinolytic components of horses undergoing laparotomy. Plasma and peritoneal fluid values of anesthetized control horses did not change. PMID- 1892268 TI - Effects of a proprietary topical medication on wound healing and collagen deposition in horses. AB - Full-thickness skin wounds were created on the dorsum of both metacarpi in 8 horses. Three topical treatment regimens were studied. All wounds were bandaged with a nonadherent dressing, which was held in place with a snug elastic wrap. Group-A wounds were treated with a proprietary topical wound medication that consisted of a spray and an ointment. Group-B wounds were treated with the same regimen, except the putative active ingredients in the ointment were omitted. Group-C wounds were treated with a dry nonadherent bandage only. Wound dressings were changed every day and the limbs were photographed every other day until the wounds were healed. Specimens of normal skin and biopsy specimens of healed wounds were examined histologically and were assayed for hydroxyproline content. Wound healing measurements quantitated for each wound were number of days to healing, maximal wound size attained, day wound contraction commenced, day epithelium first noticed, rate of wound contraction, final wound size, and fraction of the wound that healed by contraction. The cosmetic appearance of the healed wounds was also graded. Significant differences were not noticed in hydroxyproline content, histologic appearance, or any of the wound healing measurements between treatment groups. The cosmetic appearance of healed group-A and -B wounds was significantly better than the appearance of group-C wounds. The topical treatment regimens studied neither enhanced nor inhibited wound healing in this study. PMID- 1892269 TI - Cytotoxicity against autologous, allogeneic, and xenogeneic tumor targets by human recombinant interleukin-2-activated lymphocytes from healthy dogs and dogs with lung tumors. AB - Before dogs with lung tumors were treated by adoptive immunotherapy, the ability of canine blood lymphocytes (PBL) from the peripheral circulation to differentiate in vitro in the presence of human recombinant interleukin-2 (rIL-2) and become tumoricidal was investigated. The PBL from healthy dogs (n = 6) and dogs with lung tumors (n = 5) were grown in culture medium alone, in the presence of rIL-2 to generate lymphokine-activated killer (LAK) cells, or with phytohemagglutinin (PHA) and rIL-2 to generate autologous-stimulated lymphocytes (ASL). After 4 days, cytotoxicity by the ASL, LAK, and PBL was determined in a 4 hour 51chromium-release assay. Target cells in the assay were short-term cultured enzyme digests of autologous (self), allogeneic (genetically different) primary tumors, and Raji, the xenogeneic human lymphoma cell line. The PBL cultured without rIL-2 were not cytotoxic against any tumor. However, when a dog's PBL were activated in vitro, they killed the dog's own tumor, ASL more effectively than LAK cells. Pulmonary adenocarcinomas and an osteosarcoma metastasis to lung were among the autologous tumors assayed. Against an allogeneic canine osteosarcoma, ASL generated from healthy dogs were significantly more cytolytic than LAK from healthy dogs, or than ASL generated from tumor-bearing dogs. Cytotoxicity was greater against allogeneic tumor than against Raji. Lectin dependent cellular cytotoxicity, tested by including PHA in the assay medium with lymphocytes and Raji cells, by ASL and LAK was greater than cytotoxicity of Raji without PHA. Because ASL were more cytolytic than LAK against all targets in vitro, they may be more beneficial than LAK for immunotherapy of canine tumors. PMID- 1892270 TI - Culture and morphologic features of small intestinal mucosal explants from weaned pigs. AB - Small intestinal explants from weaned pigs were cultured under a variety of conditions. Explants maintained villus-to-crypt ratio between 1:1 and 1.5:1 for 48 hours. The mucosal epithelium remained well preserved and retained good cellular morphologic features, as determined by light and electron microscopy. Between 48 and 72 hours, considerable mucosal degeneration was evident. Best results were obtained when the explants were cultured on a rocking platform placed in an atmosphere of 95% O2 and 5% CO2, using supplemented RPMI 1640 cell culture medium. PMID- 1892271 TI - Differences in signs and lesions in sheep and goats with enterotoxemia induced by intraduodenal infusion of Clostridium perfringens type D. AB - Enterotoxemia was induced in 4 lambs and 4 goat kids by continuous intraduodenal infusion of a whole culture of Clostridium perfringens type D. Clinical signs, hematologic values, biochemical alterations, and postmortem lesions in the lambs and goat kids were compared. The 4 lambs and 4 goat kids died within 25 hours of beginning the infusions. Lesions were not observed in the gastrointestinal tract of the 4 lambs; however, severe hemorrhagic enterocolitis was found in the 4 goat kids. This difference between the lambs and goat kids in the lesions caused by experimentally induced enterotoxemia may explain the discrepancies reported between sheep and goats in clinical signs, response to treatment, and efficacy of vaccination observed in naturally induced enterotoxemia in the 2 species. PMID- 1892272 TI - Effects of xylazine butorphanol on cecal arterial blood flow, cecal mechanical activity, and systemic hemodynamics in horses. AB - A chronic model with an ultrasonic transit time blood flow probe and strain gauge force transducers implanted on the cecum was used to evaluate cecal mechanical activity and cecal arterial blood flow in 4 conscious adult horses. Intravenous administration of xylazine (1.1 mg/kg of body weight) significantly decreased heart rate and cardiac output, but significantly increased diastolic pulmonary arterial pressure, mean pulmonary arterial pressure, carotid arterial pressure, and central venous pressure. Lateral cecal arterial blood flow after xylazine administration was decreased substantially more than was cardiac output, suggesting that xylazine caused constriction of the cecal vasculature. This effect of xylazine may have resulted from either a direct effect of xylazine on the cecal vasculature or from reflex vasoconstriction attributable to reduced cardiac output. Intravenous administration of butorphanol tartrate (0.1 mg/kg) did not significantly alter the hemodynamic responses to xylazine. Cecal mechanical activity, as measured by the motility index, was decreased for 120 minutes after administration of xylazine and for 150 minutes after administration of xylazine/butorphanol. PMID- 1892273 TI - Kinetics of uptake and effects of topical indomethacin application on protein concentration in the aqueous humor of dogs. AB - The pharmacokinetic properties of indomethacin and its effects on aqueous protein values were studied in 15 clinically normal Beagles. The dogs were treated every 6 hours with 1% indomethacin suspension in 1 eye, with the other eye serving as a control. After 24 hours, the dogs were anesthetized and samples of aqueous humor (AH) were drawn by aqueocentesis at 0, 15, 30, 60, and 90 minutes after initial paracentesis. Additional samples were drawn at the time of euthanasia, 180 (6 dogs) and 360 minutes (9 dogs) minutes after initial paracentesis. Blood samples were obtained at each treatment and at each aqueocentesis. The eyes were enucleated after dogs were euthanatized. Aqueous protein concentrations and indomethacin concentrations in AH, plasma, and different ocular tissues were determined. Topical indomethacin administration had no effect on baseline protein concentrations of AH. It reduced protein concentrations in AH significantly at all times after initial aqueocentesis. This reduction was approximately 30%. Indomethacin in the AH is mostly protein-bound. Concentrations were 350 ng/ml in primary AH and 1,305 ng/ml in secondary AH, 90 minutes after initial aqueocentesis. Free-drug concentrations were relatively constant at about 220 ng/ml. Indomethacin administered topically is readily absorbed by the ocular adnexae, reaching a steady-state concentration of 25 ng/ml in blood plasma 18 hours after the start of treatment. Plasma concentrations were 50 times lower than therapeutically effective concentrations. High indomethacin concentrations were found in the cornea only. Low concentrations were found in the iris and ciliary body, the lens, and in the choroid.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1892274 TI - High sulfide concentrations in rumen fluid associated with nutritionally induced polioencephalomalacia in calves. AB - Nine 115- to 180-kg, hay-adapted, Holstein steers were fed an experimental diet with added sodium sulfate that induces polioencephalomalacia (PEM). Five calves developed the disease. Thiamine concentrations in blood, CSF, brain, and liver were not indicative of thiamine deficiency. The odor of hydrogen sulfide in eructated rumen gas was associated with the onset of PEM. Sulfide concentrations in rumen fluid were measured 1 or 2 times a week by 2 techniques. Sulfide concentrations progressively increased in all 9 calves after the feeding of the PEM-inducing diet commenced. The highest concentrations coincided with the onset of clinical signs of PEM and were significantly higher in the calves that developed PEM than in those that did not. This suggests that PEM can result from sulfide toxicosis following excess production of sulfide in the rumen. PMID- 1892275 TI - Assessment of toxicosis induced by high-dose administration of milbemycin oxime in collies. AB - Fifteen Collies, previously having mild reactions to ivermectin challenge (120 micrograms/kg of body weight; 20 times the recommended dosage level), were studied to evaluate the effects of milbemycin oxime administration at 5 and 10 mg/kg (10 and 20 times the manufacturer's recommended dosage). Five replicates, comprising 3 dogs each, were formed on the basis of body weight. Within replicates, each dog was randomly allocated to treatment with 5 or 10 mg of milbemycin/kg or served as a untreated control. Dogs were examined repeatedly for signs of toxicosis for 4 days after treatment and daily thereafter. Two of 5 dogs treated at 5 mg/kg (10x) developed signs of mild depression on the day of treatment, but were normal 24 hours after treatment. All 5 dogs treated at 10 mg/kg (20x) developed signs of mild depression and ataxia by 6 hours. Signs persisted for 24 hours in 3 dogs. Two of these dogs also had mydriasis, whereas 3 salivated excessively. All dogs recovered completely by day 2 after treatment. The results of this study demonstrated that Collies sensitive to the effects of 120 micrograms of ivermectin (20x)/kg show similar sensitivity to the effects of milbemycin oxine administered at 10 mg/kg (20x). We conclude that ivermectin and milbemycin commercial formulations have similar margins of safety and that milbemycin toxicosis appears to be dose-dependent in Collies with a demonstrated sensitivity to ivermectin. PMID- 1892276 TI - Gross and histologic study of the rostral epidural rete mirabile and the cavernous sinus in one-humped camels. AB - Gross and histologic features of the rostral epidural rete mirabile (carotid rete) and the cavernous sinus in one-humped camels were studied. It was evident that the branches of the carotid rete share a common tunica adventitia with the veins of the cavernous sinus. Transmission electron microscopy of the rostral epidural rete mirabile and the cavernous sinus revealed gap junctions in endothelial cells lining the walls of the arterial rete branches and veins. The internal elastic lamina of rete branches were fenestrated. Some of these structural features could facilitate countercurrent heat exchange between the rete branches and the venous plexus of the cavernous sinus to regulate brain temperature. PMID- 1892277 TI - Fecundity of gastrointestinal trichostrongylid nematodes of sheep in the field. AB - Twenty-two Dorset Rambouillet lambs were moved to contaminated pasture on Apr 1, 1987. At regular intervals thereafter, pairs of lambs were withdrawn and euthanatized. Gastrointestinal parasites in the abomasum, small intestine, cecum, and large intestine were removed and counted. The last pair of lambs was euthanatized 8 months after original placement on the contaminated pasture. Fecal samples were taken at 3- to 4-week intervals throughout the grazing season and the fecal egg counts were used to estimate parasite fecundity (output of eggs per female parasite per day). The principal parasite genera found included Haemonchus spp, Trichostrongylus spp, and Nematodirus spp. In each of the genera examined, parasite fecundity remained the same irrespective of the intensity or duration of infection. Estimated average fecundities (eggs/female/day) were as follows: Haemonchus contortus, 6,582; Trichostrongylus spp, 262; Nematodirus spp, 40; and Oesophagostomum venulosum, 11,098. PMID- 1892278 TI - Hemodynamic response of endotoxemic calves to treatment with small-volume hypertonic saline solution. AB - The hemodynamic effects of hypertonic saline solution (HSS) resuscitation on endotoxic shock were examined in pentobarbital-anesthetized calves (8 to 20 days old). Escherichia coli (055:B5) endotoxin was infused IV at dosage of 0.1 microgram/kg of body weight for 30 minutes. Endotoxin induced large decreases in cardiac index, stroke volume, maximal rate of change of left ventricular pressure (+dP/dtmax), femoral and mesenteric arterial blood flow, glomerular filtration rate, urine production, and mean aortic pressure. Severe pulmonary arterial hypertension and increased pulmonary vascular resistance were evident at the end of endotoxin infusion. Treatment with HSS (2,400 mosm of NaCl/L, 4 ml/kg) or an equivalent sodium load of isotonic saline solution (ISS: 300 mosm of NaCl/L, 32 ml/kg) was administered 90 minutes after the end of endotoxin administration. Both solutions were infused IV over a 4- to 6-minute period. Administration of HSS induced immediate and significant (P less than 0.05) increase in stroke volume and central venous pressure, as well as significant decrease in pulmonary vascular resistance. These effects were sustained for 60 minutes, after which all variables returned toward preinfusion values. The hemodynamic response to HSS administration was suggestive of rapid plasma volume expansion and redistribution of cardiac output toward splanchnic circulation. Plasma volume expansion by HSS was minimal 60 minutes after resuscitation. Administration of ISS induced significant increase in cardiac index, stroke volume, femoral arterial blood flow, and urine production. These effects were sustained for 120 minutes, at which time, calves were euthanatized. Compared with HSS, ISS induced sustained increase in mean pulmonary arterial pressure and only a small increase in mesenteric arterial blood flow.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1892279 TI - Respiratory, renal, hematologic, and serum biochemical effects of hypertonic saline solution in endotoxemic calves. AB - The respiratory, renal, hematologic, and serum biochemical effects of hypertonic saline solution (HSS) treatment were examined in 12 endotoxic, pentobarbital anesthetized calves (8 to 20 days old). Escherichia coli endotoxin (055:B5) was infused IV at a rate of 0.1 microgram/kg of body weight over 30 minutes. Endotoxin induced severe respiratory effects, with marked hypoxemia and increases in arterial-alveolar O2 gradient (P[A-a]O2), physiologic shunt fraction (Qs/Qt), and physiologic dead space to tidal volume ratio (Vd/Vt). Oxygen consumption was decreased, despite an increase in the systemic O2 extraction ratio. Peak effects were observed at the end of endotoxin infusion. The renal response to endotoxemia was characterized by a decrease in free-water reabsorption and osmotic clearance, as well as a decrease in sodium and phosphorus excretion. Endotoxemia induced leukopenia, thrombocytopenia, hyperphosphatemia, hypoglycemia, acidemia, and increased serum alkaline phosphatase concentrations. Calves were treated with HSS (2,400 mosm/L of NaCl, 4 ml/kg, n = 4) or an equivalent sodium load of isotonic saline solution (ISS; 300 mosm/L of NaCl, 32 ml/kg, n = 4 90 minutes after the end of endotoxin administration. Both solutions were infused over a 4- to 6 minute period. A control group (n = 4) was not treated. Infusion of HSS or ISS failed to induce a significant change in Pao2, P(A-a)O2, (Qs/Qt), (Vd/Vt), or oxygen consumption. Both solutions increased systemic oxygen delivery to above pre-endotoxin values. Hypertonic saline infusion induced significant (P less than 0.05) increases in serum Na and Cl concentrations and osmolality, whereas ISS induced a significant increase in serum Cl concentration and a significant decrease in serum phosphorus concentration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1892280 TI - In vitro responses of distal airways in horses with recurrent airway obstruction. AB - Distal airway segments (ID, 3 to 4 mm; length, 5 mm) from 2 groups of horses were isolated and suspended in tissue baths filled with Krebs solution, aerated with 5% CO2 in oxygen and maintained at 37 degrees C. Responses to exogenous acetylcholine, isoproterenol, or electrical field stimulation were compared. Control horses (n = 30) had no history of recurrent airway obstruction, whereas principal horses (n = 15) had recurrent airway obstruction and were studied during an acute episode of airway obstruction. Although the distal airways contracted in response to the cumulative half-logarithmic addition of acetylcholine (10(-10) M to 10(-3) M) in both groups, bronchi obtained from principals were less sensitive to acetylcholine than were bronchi obtained from controls. Tetdrodotoxin-sensitive electrical field stimulation-induced contractions were observed in both groups of airways, but the tension achieved in principal bronchi was less than in controls. All electrical field stimulation induced contractions were abolished by atropine, indicating that the only excitatory innervation of equine distal airway is through the parasympathetic system. To examine the effect of isoproterenol and determine inhibitory innervation, bronchi were precontracted with histamine. Electrical field stimulation did not cause relaxation of precontracted bronchi in either group, thus indicating that distal airways lack inhibitory innervation. Isoproterenol caused similar, dose-dependent relaxation in both groups. PMID- 1892281 TI - The diagnosis of asbestosis. PMID- 1892282 TI - Is sleep-disordered respiration part of pulmonary medicine? PMID- 1892283 TI - Effect of alterations in mental activity on the breathing pattern in healthy subjects. AB - The overall output from the respiratory centers is regulated by an automatic metabolic control system in the brainstem and by higher neural centers under direct voluntary control. An understanding of the constancy with which respiration is controlled can be obtained by measuring the breath-to-breath variability in breathing pattern. We hypothesized that different forms of mental activity would alter the variability of breathing pattern. To test this hypothesis, we measured breathing pattern on a breath-by-breath basis during resting wakefulness and during four conditions of altered mental activity. Measurements were obtained with a calibrated respiratory inductive plethysmograph, and variability was assessed by calculations of the coefficients of variation. We also examined the effect of the altered states of mental activity on the mean values of the breathing pattern components. We found that noxious stimulation increased the variability of all the breathing pattern indices, audiovisual stimulation tended to increase the variability of tidal volume (VT), and mental arithmetic had no effect. In addition, the variability of breathing pattern was increased during rapid eye movement sleep and decreased during Stage IV sleep. The variability of VT and expiratory time were greater than that of inspiratory time (TI) across the different states of mental activity. Significant correlations were observed between VT and TI and between VT and frequency (f) during Stage IV sleep. With regards to the mean values, mental arithmetic, audiovisual stimulation, and noxious stimulation all increased minute ventilation and mean inspiratory flow.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1892284 TI - Effect of acute fasting on diaphragm strength and endurance. AB - The effects of short periods of fasting on diaphragm contractile function remain unclear. The purpose of the present study was (1) to examine the relationship between duration of acute fasting and diaphragm contractile performance, and (2) to assess the effects of fasting on diaphragm glycogen stores and the relationship between changes in diaphragm function and alterations in muscle glycogen stores. Studies were performed on four groups of Syrian hamsters (nine animals in each group). One group served as a control and was allowed to feed normally, whereas the other three groups were fasted for either 1, 2, or 3 days. Diaphragm strips from animals were studied in vitro by measuring tension during electrically induced contractions. Two strips from each animal were studied; one strip was examined with a bath glucose equal to the prevailing blood glucose, and the second was preincubated in a high glucose solution (170 mg/dl) for 20 min. Fasting resulted in reductions in body weight, blood glucose concentrations, diaphragm strength, and diaphragm endurance in strips tested at the prevailing blood glucose levels. These effects were pronounced in animals fasted for 3 days, with little or no change in diaphragm contractility observed in animals fasted for shorter periods. Diaphragm weight, thickness, and glycogen content were unchanged in the fasted animals, as was the weight of the soleus muscle. Preincubation of strips from 3-day-fasted animals in a high glucose medium resulted in a significant increase in diaphragm strip strength and endurance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1892285 TI - Effect of weight loss on upper airway collapsibility in obstructive sleep apnea. AB - Previous investigators have demonstrated in patients with obstructive sleep apnea that weight reduction results in a decrease in apnea severity. Although the mechanism for this decrease is not clear, we hypothesize that decreases in upper airway collapsibility account for decreases in apnea severity with weight loss. To determine whether weight loss causes decreases in collapsibility, we measured the upper airway critical pressure (Pcrit) before and after a 17.4 +/- 3.4% (mean +/- SD) reduction in body mass index in 13 patients with obstructive sleep apnea. Thirteen weight-stable control subjects matched for age, body mass index, gender (all men), and non-REM disordered breathing rate (DBR) also were studied before and after usual care intervention. During non-REM sleep, maximal inspiratory airflow was measured by varying the level of nasal pressure and Pcrit was determined by the level of nasal pressure below which maximal inspiratory airflow ceased. In the weight loss group, a significant decrease in DBR from 83.3 +/- 31.0 to 32.5 +/- 35.9 episodes/h and in Pcrit from 3.1 +/- 4.2 to -2.4 +/- 4.4 cm H2O (p less than 0.00001) was demonstrated. Moreover, decreases in Pcrit were associated with nearly complete elimination of apnea in each patient whose Pcrit fell below -4 cm H2O. In contrast, no significant change in DBR and a minimal reduction in Pcrit from 5.2 +/- 2.3 to 4.2 +/- 1.8 cm H2O (p = 0.031) was observed in the "usual care" group. We conclude that (1) weight loss is associated with decreases in upper airway collapsibility in obstructive sleep apnea, and that (2) the resolution of sleep apnea depends on the absolute level to which Pcrit falls. PMID- 1892286 TI - Influence of posture and sustained loss of lung volume on pulmonary function in awake asthmatic subjects. AB - Nocturnal worsening occurs commonly in the asthmatic patient population and contributes substantially to the morbidity and even mortality of asthma. However, no physiologic process has yet been identified as the major contributor to this pattern. Sleep is typically associated with both the supine posture and substantial decrements in lung volume, and both have been proposed to have a role in the pattern of nocturnal worsening. To assess the effects of posture and sleep associated reductions in functional residual capacity on pulmonary function, eight asthmatic patients were first monitored overnight in a horizontal volume displacement body plethysmograph to determine mean FRC during sleep for each subject. We then compared, during wakefulness, the effects on FEV1 and methacholine responsiveness from chest wall and abdomen strapping (to maintain FRC at mean sleep levels) for 6 h in the supine and upright postures. FEV1 was significantly decreased after strapping in the supine posture (2.54 +/- 0.36 versus 3.38 +/- 0.29 L on control day, p = 0.0001) but was not affected by strapping in the upright posture (3.07 +/- 0.30 versus 3.34 +/- 0.31 L on control day, not significant, NS). Bronchial responsiveness to methacholine was not altered after strapping in either posture. These observations suggest that the supine posture, in conjunction with the reduction in lung volume associated with sleep, may contribute to the nocturnal worsening of asthma. PMID- 1892287 TI - The influence of cigarette smoking on lung function in patients with idiopathic pulmonary fibrosis. AB - The purpose of this investigation was to quantify the effect of cigarette smoking on standard measures of lung function in patients with idiopathic pulmonary fibrosis (IPF). Our study population consisted of 73 patients in whom IPF had been clinically diagnosed; in 67% the diagnosis was confirmed by open lung biopsy. The average age was 63 yr; 62% were men, and 70% were either former or current cigarette smokers. Current cigarette smokers were found to have a greater percent predicted residual volume. Interestingly, in a univariate analysis, pack years of cigarette smoking was found to be directly associated with increased measures of lung volumes (TLC, FRC, and RV) and diminished gas exchange (DLCO). Linear multivariate regression models demonstrated that current cigarette smokers have greater measures of RV and FRC and that increasing pack-years of cigarette smoking is associated with diminished gas exchange. Importantly, the FEV/FVC ratio was not significantly related to either smoking status or pack-years of cigarette smoking. Results from our study indicated that among patients with IPF, current cigarette smokers will tend to trap air (higher RV and FRC), and that cigarette smoking appears to adversely alter gas exchange. Moreover, IPF appears to reduce the likelihood of developing physiologic correlates of airflow obstruction among cigarette smokers. However, this does not imply that IPF prevents the development of cigarette-induced lung disease. In fact, the association between cigarette smoking and both increased lung volumes and diminished gas exchange suggests the presence of both emphysema and interstitial fibrosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1892288 TI - Changes in end-expiratory lung volume during exercise in cystic fibrosis relate to severity of lung disease. AB - Changes in end-expiratory lung volume (EELV) during exercise in normal subjects and in patients with severe chronic obstructive lung disease have previously been examined. To date there are no studies that have examined the changes in EELV in patients with mild to moderate lung disease. We studied the changes in EELV during exercise in patients with cystic fibrosis (CF) with a wide range of pulmonary impairment to determine if changes in EELV were related to the severity of lung disease. Twenty-two patients with CF were studied (FEV1 17 to 112% of predicted) during progressive bicycle exercise, and changes in EELV were determined by repeat measures of inspiratory capacity. Changes in EELV at end exercise ranged from an increase of 0.67 L to a decrease of 0.61 L, and significant relationships were found between the changes in EELV and resting lung function (FEV1 percent predicted r = 0.79 and VR/TLC r = 0.58), indices of maximal expiratory flow (FEF50 r = -0.72 and FEF25-75 r = -0.71), and maximal work capacity (W-Max r = -0.76 and W-Max percent predicted r = -0.69). For subsequent analysis, patients were divided into two subgroups. Patients who were able to decrease EELV during exercise (Subgroup A) had significantly better resting lung function and SaO2 and significantly higher W-Max, peak oxygen consumption, and SaO2 at W-Max. Patients in Subgroup A also had a near normal ventilatory pattern during exercise. In contrast, the patients who increased EELV during exercise (Subgroup B) had severe lung disease (mean FEV1 29 +/- 4 percent predicted), limited work capacity, and desaturated during exercise.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1892289 TI - Moment analysis of a multibreath nitrogen washout based on an alveolar gas dilution number. AB - A common method for analyzing a multibreath nitrogen washout (MBNW) is to perform moment analysis and derive the mean dilution number (MDN). A homogeneously mixed alveolar space with zero series dead space (VD = 0) will always result in a MDN = 1, regardless of breathing pattern. A higher MDN implies more inhomogeneity. But, if VD greater than 0, the MDN can become sensitive (artificially high) to VD/VT ratios. We present an alveolar-based mean dilution number (AMDN) that uses the cumulative expired alveolar volume. Unlike the MDN, the AMDN for a homogeneously mixed alveolar space is unity, regardless of VD or VT, and hence should be a more appropriate index of inhomogeneity at the alveolar level. Two sets of experiments were used to compare the AMDN with the MDN. First, a MBNW was performed by five healthy subjects at spontaneous VD/VT and at a low VD/VT achieved by a controlled increase in VT. Here, the MDN decreased from 1.98 +/- 0.1 to 1.79 +/- 0.06, whereas the AMDN was essentially unchanged (1.42 +/- 0.04 to 1.38 +/- 0.06). Second, MBNW values from seven healthy subjects, five with cystic fibrosis, and 10 asthmatic subjects (before and after bronchodilation) were analyzed. Compared with the MDN, the AMDN showed a significantly wider separation between clinical groups. Also, the AMDN demonstrated an increased variability within both sick groups versus a decrease in the healthy group. We conclude that the AMDN is superior to the MDN because of its decreased sensitivity to breathing pattern but increased sensitivity to degree of disease. PMID- 1892290 TI - Gas exchange during exercise in mild chronic obstructive pulmonary disease. Correlation with lung structure. AB - To investigate whether or not the pathologic features in the lungs of patients with chronic obstructive pulmonary disease (COPD) are related to the gas exchange response during exercise, we studied 17 patients (15 men, two women) with mild-to moderate airflow obstruction (FEV1/FVC ratio, 59 +/- 3%), undergoing resective lung surgery, at rest and during submaximal exercise (71 +/- 5% predicted VO2max). During exercise, arterial PO2 increased (from 81 +/- 3 to 86 +/- 3 mm Hg, p less than 0.05) as a result of an overall improvement in VA/Q relationships. This improvement included an increase in the mean VA/Q ratios of both ventilation and blood flow distributions, and a more homogeneous ventilation distribution (logSD V, from 0.66 +/- 0.06 to 0.50 +/- 0.03; p less than 0.01; normal value, less than or equal to 0.6). The morphologic evaluation of the resected specimens disclosed a moderate degree of emphysema (emphysema score, 16 +/- 4) and mild abnormalities in membranous bronchioles (total pathology score, 107 +/- 8). At rest, significant correlations were found between the severity of the pathologic findings and both the degree of hypoxemia and the extent of VA/Q mismatching. During exercise, no relationship between bronchiolar abnormalities and gas exchange measurements was observed, whereas the severity of emphysema was correlated with PaO2 (r = -0.54, p less than 0.05). Both the overall increase in and the more efficient distribution of ventilation accounted for the improvement in VA/Q distributions during exercise. These changes were more pronounced in patients with a greater degree of bronchiolar abnormalities.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1892291 TI - Evaluation of a new weaning index based on ventilatory endurance and the efficiency of gas exchange. AB - We hypothesized that the ventilatory capacity needed to wean from mechanical ventilation (mv) depends on two variables: ventilatory endurance and the efficiency of gas exchange. We also hypothesized that these variables could be assessed from data readily available at the bedside, including tidal volume (VT) on mv and during spontaneous breathing (sb), ventilator peak inspiratory pressure (Ppk), and patient negative inspiratory pressure (NIP). Ventilatory endurance was evaluated using a modified pressure-time index: PTI = TI/Ttot x Pbreath/NIP, where Pbreath = Ppk x VTsb/VTmv. Defining VE40 as the minute ventilation needed to bring PaCO2 to 40 mm Hg, the efficiency of gas exchange was evaluated by calculating VE40/VTsb = (VE x PaCO2)mv/VTsb x 40. Because high levels of inspiratory effort might cause patients to reduce VTsb and thereby compromise CO2 elimination, we devised a weaning index (WI) that combines ventilatory endurance and the efficiency of gas exchange: WI = PTI x (VE40/VTsb). The study population comprised 38 patients with chronic obstructive pulmonary disease, adult respiratory distress syndrome, pneumonia, neuromuscular disease, and miscellaneous other conditions. They had been mechanically ventilated more than 3 days and were considered by clinical criteria to be ready for weaning. Of 46 weaning trials, 19 were successful, 2 were partially successful, and 25 failed. PTI and VE40/VTsb were higher in patients who failed (p less than 0.05), but neither variable alone had sufficient sensitivity or specificity to predict the outcome of weaning trials accurately.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1892292 TI - Effects of positive end-expiratory pressure, lung volume, and inspiratory flow on interrupter resistance in patients with adult respiratory distress syndrome. AB - Although it has been shown in normal subjects that airway resistance changes significantly with changes in lung volume and inspiratory flow, no studies have as yet examined these phenomena in patients with adult respiratory distress syndrome (ARDS). The effect of positive end-expiratory pressure (PEEP) on airway resistance in ARDS also is unknown. We have used the technique of rapid airway occlusion during constant-flow inflation to measure the interrupter resistance (Rint,rs), which in humans is thought to correspond to airway resistance, in nine patients with ARDS under different inflation flows and volumes. This procedure was carried out at four levels of PEEP (0, 5, 10, and 15 cm H2O). We found that (1) at constant inflation volume, Rint,rs did not change significantly with increasing flow; (2) at constant inflation flow, Rint,rs showed an initial decrease followed by a distinct rise with increasing lung volume; (3) on average, PEEP did not significantly change Rint,rs measured during baseline ventilation; and (4) this latter finding occurred because patients behaved differently with application of PEEP, depending on their degree of lung inflation: Rint,rs measured close to full inflation almost invariably exhibited a rise, but values obtained at lower volumes exhibited the characteristic decrease of Rint,rs with increasing inflation volume. PMID- 1892293 TI - Effects of positive end-expiratory pressure on alveolar recruitment and gas exchange in patients with the adult respiratory distress syndrome. AB - The effects of different levels of positive end-expiratory pressure (PEEP) (zero to 15 cm H2O) on the static inflation volume-pressure (V-P) curve of the respiratory system and on gas exchange were studied in eight patients with the adult respiratory distress syndrome (ARDS). Alveolar recruitment with PEEP was quantified in terms of recruited volume, i.e., as difference in lung volume between PEEP and zero end-expiratory pressure (ZEEP) for the same static inflation pressure (20 cm H2O) from the V-P curves obtained at the different PEEP levels. In addition, static compliance of the respiratory system at fixed tidal volume (0.7 L) was determined at the different PEEP levels. The results suggest that: (1) in some patients with ARDS the V-P curves determined on ZEEP exhibit an upward concavity reflecting progressive alveolar recruitment with increasing inflation volume, and PEEP results in alveolar recruitment (range of recruited volume at 15 cm H2O of PEEP: 0.11 to 0.36 L); (2) in other patients with ARDS the V-P curves on ZEEP are characterized by an upward convexity, and PEEP results in a volume displacement along this curve without alveolar recruitment and with enhanced risk of barotrauma; (3) the PEEP-induced increase in arterial oxygenation is significantly correlated to the recruited volume but not to the changes in static compliance. The shape of the static inflation V-P curves on ZEEP allows the prediction of alveolar recruitment with PEEP. PMID- 1892294 TI - Survival of patients with acquired immune deficiency syndrome and disseminated Mycobacterium avium complex infection with and without antimycobacterial chemotherapy. AB - The contribution of disseminated Mycobacterium avium complex (DMAC) infection to the morbidity and mortality of patients with acquired immune deficiency syndrome (AIDS) is unclear. Previous studies that suggested the decreased survival of patients with AIDS and DMAC had incomplete information on patient immunologic status and follow-up. We studied patients with AIDS and DMAC and compared their survival with that of AIDS patients without DMAC but with other comparable risk factors for survival. Case and control subjects were similar in terms of CD4 cell count, prior AIDS status, history of antiretroviral therapy, history of Pneumocystis carinii prophylaxis, and year of diagnosis. A group of 39 patients with untreated DMAC had significantly shorter survival, mean of 5.6 +/- 1.1 months (median 4 months), than 39 matched patients with AIDS but without DMAC, mean 10.8 +/- 1.3 months (median 11 months, p less than 0.0001). The survival of 16 additional patients with DMAC who received antimycobacterial therapy, mean of 9.5 +/- 1.4 months (median 8 months), was not significantly shorter than that of an additional 16 matched control subjects, mean 11.7 +/- 1.9 months (median 11 months, p = 0.58). Patients with treated DMAC survived significantly longer than those with untreated DMAC (p less than 0.01). We conclude that untreated DMAC significantly shortens survival. Moreover, these results indicate that patients with DMAC who receive antimycobacterial therapy do not experience the shortened survival seen in untreated DMAC. PMID- 1892295 TI - Stability of positive tuberculin tests: are boosted reactions valid? AB - To determine the stability and presumed significance of tuberculin skin tests, we followed a cohort of 380 tuberculin-positive patients living in chronic care facilities. Each patient had a positive reaction (greater than or equal to 10 mm induration to 5 tuberculin units of purified protein derivative) to one of three sequential baseline tuberculin tests. One year after the initial series, each patient had a single repeat skin test. Reversion to a negative test occurred in 98 (26%) of the 380 patients. Decreases in induration of 6 mm or more occurred in 88 (90%) of the reverters. Initially positive tests were more likely (p less than 0.001) to remain stable than tests that were "boosted" to positive reactions on the second or third initial administration. Stable responses were found in 96% of those whose tests had greater than or equal to 15 mm induration compared with 61% of those with reactions of 10 to 14 mm induration. Increasing age also was associated with a high rate of reversion. The instability of boosted tuberculin reactions brings into question the clinical significance of these tests. We propose limiting tuberculin testing to two sequential tests. PMID- 1892296 TI - Passive smoking by humans sensitizes circulating neutrophils. AB - The proinflammatory effects of passive inhalation of cigarette smoke were investigated by exposing a total of 16 healthy, young nonsmokers (mean age 29 +/- 1.4 yr, 11 women and five men) to actively smoking individuals in a poorly ventilated room. Neutrophil functions were measured before and after 3 h of exposure to cigarette smoke. Passive cigarette smoking was associated with increased leukocyte counts (mean increase 33%, p less than 0.005), chemotaxis (57%, p less than 0.001), and release of reactive oxidants (71%, p less than 0.005) by stimulated neutrophils. These results were confirmed in a second study designed to eliminate the possible complicating effects of serial venepuncture. Plasma concentrations of the proinflammatory cytokines interleukin-1 (IL-1) alpha, IL-1 beta, IL-6, and tumor necrosis factor alpha (TNF alpha) were not affected by passive smoking. These results indicate that inhalation of sidestream tobacco smoke promotes systemic priming of neutrophils. These potentially proinflammatory events may induce oxidant-mediated tissue damage and carcinogenesis in the lungs of passive smokers. PMID- 1892297 TI - Therapeutic efficacy of liposome-encapsulated kanamycin against Mycobacterium intracellulare infection induced in mice. AB - Liposome-encapsulated kanamycin (KM) was examined for therapeutic efficacy against experimental infection induced with Mycobacterium intracellulare in mice. Liposomal KM injections (once weekly for up to 8 wk) led to a greater reduction in the degree of gross pulmonary lesions and in the growth of the organisms in the visceral organs (lungs, liver, spleen, and kidneys) of infected mice than did either free KM alone or free KM mixed with empty liposomal vesicles. The therapeutic effect of the liposome-encapsulated KM was dose dependent for doses from 50 to 200 micrograms KM/mouse/injection. Liposome encapsulation markedly changed the tissue distribution of KM, in particular in the reticuloendothelial organs, such as liver and spleen. In these organs, accumulation and retention of liposome-entrapped KM was remarkably higher than that of free KM. Moreover, considerably prolonged retention was seen for liposome-encapsulated KM in serum and lungs. Encapsulation of KM into liposomal vesicles increased incorporation of the drug into the host peritoneal macrophages and enhanced the antimicrobial activity of the agent against M. intracellulare phagocytosed into macrophages. PMID- 1892298 TI - Human neutrophil elastase and elastase/alpha 1-antiprotease complex in cystic fibrosis. Comparison with interstitial lung disease and evaluation of the effect of intravenously administered antibiotic therapy. AB - In cystic fibrosis (CF), extracellular lung matrix is progressively damaged, neutrophils invade the air spaces, and activated neutrophils may release large amounts of neutrophil elastase (NE). Although alpha 1-antiprotease (alpha 1-AP) binds and inactivates NE and is the major antielastase of the lower respiratory tract, antielastase defenses may be overwhelmed in CF, leading to progressive lung damage. To determine whether the ability of alpha 1-AP to neutralize NE is impaired in CF, we compared NE activity in bronchoalveolar lavage (BAL) fluid and human neutrophil elastase/alpha 1-antiprotease (NE/alpha 1-AP) complex in both BAL fluid and peripheral blood serum from patients with CF, normal volunteers, and patients with interstitial lung disease. We detected a considerable amount of NE activity in BAL fluid from all but one patient with CF but none in that from normal volunteers or from patients with interstitial lung disease. Although in interstitial lung disease there was a significant correlation between increased NE/alpha 1-AP complex in BAL or peripheral blood and the degree of neutrophil influx, NE/alpha 1-AP complex was disproportionately low in CF BAL compared with significantly elevated values in serum. These data suggest that in CF, alpha 1-AP mediated defense against free NE in the lower respiratory tract is significantly impaired, and high levels of uncomplexed, enzymatically active, NE are present in CF respiratory secretions. To determine whether intravenously administered antipseudomonal antibiotic therapy for exacerbations of CF lung disease diminished the amount of free NE in respiratory secretions, we used BAL to investigate the effect of such therapy on neutrophils and NE in patients with CF colonized with pseudomonads.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1892299 TI - Methylprednisolone achieves greater concentrations in the lung than prednisolone. A pharmacokinetic analysis. AB - Previous studies in humans and rabbits demonstrated that methylprednisolone appears in the lung in greater concentration than prednisolone. To ascertain which pharmacokinetic properties of these drugs explain this difference, we gave methylprednisolone and prednisolone, 5 mg/kg intravenous bolus, to 23 adult rabbits. To measure the plasma concentration versus time curves for methylprednisolone and prednisolone, samples were obtained predose through 480 min postdose. To measure the bronchoalveolar lavage glucocorticoid concentration versus time curves, lavage was performed once per experiment at seven separate time points from 5 to 480 min post-dose (two to four experiments per time point). Bronchoalveolar lavage fluid (BALF) recovery ranged from 50 to 75% and was similar in both groups. Glucocorticoid concentration in plasma and BALF was determined by high performance liquid chromatography. To normalize for the dilutional effects of lavage, epithelial lining fluid (ELF) recovery was quantitated from BALF volume and BALF and plasma urea concentrations. Pharmacokinetic parameters of the two glucocorticoids were calculated both noncompartmentally and by a three-compartment model. The extrapolated plasma glucocorticoid concentrations at time zero of methylprednisolone and prednisolone are similar, but the volume of distribution and plasma half-life of methylprednisolone are significantly greater than those of prednisolone (p less than 0.05). Although the clearance of the two drugs are not significantly different, methylprednisolone appears to have a slower Cl than prednisolone. The mean residence time (the average time drug remained in body) was significantly longer for methylprednisolone than for prednisolone (p less than 0.05), and plasma glucocorticoid concentrations became significantly different in the two groups by 90 min (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1892301 TI - T cell subsets in healthy black smokers and nonsmokers. Evidence for ethnic group as an important response modifier. AB - The influence of cigarette smoking on T cell subsets has been studied in white subjects, but comparable data are not available for blacks. We analyzed peripheral blood mononuclear cell subsets in a population-based, stratified, random sample of healthy black adults using monoclonal antibodies and flow cytometry. The study population consisted of 94 men and 79 women, including 73 smokers (CS) and 100 nonsmokers (NS). Cigarette smoking was associated with a significant elevation in leukocyte (WBC) count (CS 7,270 +/- 230 cells/mm3 versus NS 6,260 +/- 160 cells/mm3; p = 0.001), although WBC counts for both groups were substantially lower than those reported for white smokers and nonsmokers. Smokers had a significantly lower proportion of CD4+ cells than nonsmokers (CS 55.4 +/- 0.9% versus NS 58.7 +/- 0.9; p = 0.01), adjusting for age and gender. No significant smoking-related changes were observed for CD8+ cells, the CD4/CD8 ratio, or total T cells (CD3+), monocytes (CD14+), or natural killer cells (CD16+). Among black smokers, a significant dose-related decrease in CD4+ cells was observed as the number of cigarettes smoked per day increased. Among black exsmokers, the level of WBC and CD4+ cells returned to the level observed in never smokers within 2 to 5 yr after smoking cessation. These results contrast sharply with the previously reported increase in CD4+ cells and decrease in natural killer cells associated with cigarette smoking in whites. The data suggest that the immunologic effects of cigarette smoking may be significantly modified by ethnic characteristics. PMID- 1892300 TI - Simultaneous exposure of sheep to endotoxin and 100% oxygen. AB - The purpose of this study was to determine the effect of endotoxin on the development of vascular and airway dysfunction during O2 toxicity. Sheep were prepared for chronic measurement of vascular pressures, cardiac output, gas exchange, and collection of lung lymph. Tracheostomies were made for accurate delivery of gas mixtures. Sheep were placed in one of three experimental groups: those receiving endotoxin (n = 9), those breathing 100% O2 and receiving endotoxin (n = 7), and those exposed to 100% O2 alone (n = 6). Sheep had daily measurements of hypoxic vasoconstriction (FIO2 = 0.12), gas exchange, circulating white blood cell counts, lymph flow, and lymph and plasma protein concentrations. Lung neutrophils were counted, and copper-zinc superoxide dismutase and manganous superoxide dismutase were measured in lung samples from some sheep biopsies taken at baseline surgery and postmortem. Endotoxin markedly prolonged survival time and partially protected against the increased lung vascular permeability in sheep breathing 100% oxygen, but impairment of gas exchange, loss of hypoxic pulmonary vasoconstriction, and ultimate progression of respiratory failure were not prevented. Induction of MnSOD occurred in sheep breathing 100% O2, in sheep receiving endotoxin alone, and in those exposed to 100% O2 plus endotoxin. We conclude that endotoxin markedly increases tolerance to O2 toxicity but that some of the pathophysiology of O2 toxicity is unaltered. The role of superoxide dismutase in the observed protection is unclear. PMID- 1892302 TI - MK-571, a potent antagonist of leukotriene D4-induced bronchoconstriction in the human. AB - MK-571 is a novel leukotriene D4/E4 (LTD4/E4) receptor antagonist. The ability of MK-571 to inhibit LTD4-induced bronchoconstriction was examined both in six healthy volunteers and in six asthmatic subjects in a double-blind, placebo controlled, randomized crossover study design. LTD4 challenges were performed during a constant infusion with placebo or the active compound. The provocative concentration of LTD4 causing a 35% decrease in SGaw (PC35 SGaw) was 4.8 +/- 0.6 x 10(-5) M (mean +/- SEM) in healthy volunteers and 1.8 +/- 0.7 x 10(-6) M in asthmatic subjects during placebo treatment. Intravenous MK-571 (1,500, 86, or 28 mg) inhibited the LTD4-induced bronchoconstriction completely in healthy volunteers, up to an inhaled concentration of 10(-4) M LTD4. In asthmatic subjects, 28 mg MK-571 caused a significant, at least 44-fold, rightward shift of the dose-response curve to LTD4, whereas 277 mg shifted the dose-response curve at least 84-fold to the right. MK-571 is therefore a potent antagonist of LTD4 induced bronchoconstriction in both normal volunteers and asthmatic patients. MK 571 also caused a small but significant increase in baseline airway caliber in asthmatic patients, suggesting the presence of LTD4 in asthmatic airways and thus providing further support to a role for sulfidopeptide leukotrienes in the pathogenesis of asthma. PMID- 1892303 TI - A three-month comparison of twice daily inhaled formoterol versus four times daily inhaled albuterol in the management of stable asthma. AB - We compared the efficacy of inhaled formoterol, a long-acting beta 2-agonist, with inhaled albuterol in 145 stable adult asthmatics in a 12-wk multicenter trial. Patients were allocated in randomized double-blind fashion to maintenance therapy with either formoterol 12 micrograms twice a day or albuterol 200 micrograms four times a day in addition to their other asthma medications. Patients were allowed to use "rescue" 100-micrograms albuterol puffs on an as needed basis. Mean baseline FEV, in the morning before bronchodilator was 2.14 +/ 0.76 L and 1.98 +/- 0.71 L for the formoterol and albuterol groups, respectively, these values being used as baseline covariates in subsequent analysis of predrug and postdrug FEV1. Measured at each clinic visit, morning predrug FEV1 rose significantly with formoterol treatment and was significantly greater at all visits than in the albuterol group, the greatest difference being in Week 8 (2.40 +/- 0.77 versus 1.92 +/- 0.66 L, p less than 0.001). Morning FEV1 30 min postdrug was significantly higher in the formoterol group at Weeks 2 and 8, the trend not reaching statistical significance at other times. Diurnal variation in prebronchodilator peak flow rates was significantly reduced in the formoterol group throughout the trial (17 versus 42 L/min at Week 12, p less than 0.0001). The number of asthma episodes per week was significantly less in the formoterol group during Weeks 4, 8, and 12 as were the number of sleep disruptions during Weeks 2, 4, 6, 8, and 12. Significantly more rescue albuterol was required in the albuterol group by Week 2 and throughout the remainder of the study.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1892304 TI - Inhibition of neutral endopeptidase potentiates bronchial contraction induced by immune response in guinea pigs in vitro. AB - To study the role of tachykinins and neutral endopeptidase (NEP), an enzyme that degrades tachykinins, in the immune response in the airways of guinea pigs sensitized to ovalbumin (OVA), we examined the bronchial contractile response to OVA by inhibiting NEP in vitro. After incubating bronchial tissues with the NEP inhibitors phosphoramidon and thiorphan, we added 10(-5)% (10 micrograms/ml) OVA. Phosphoramidon and thiorphan (10(-5) M) significantly maintained the contraction that followed the peak contraction. In the next stages of the experiment, when the contraction induced by 10(-5)% OVA reached a plateau and began to relax, we added 10(-5) M phosphoramidon. Phosphoramidon inhibited the relaxation and significantly potentiated the contraction. In tissues treated with 10(-5) M capsaicin to deplete tachykinins, phosphoramidon did not potentiate the OVA induced contraction, but substance P (10(-6) M) caused contraction. These results suggest that the immune response causes the release of tachykinin-like substances from capsaicin-sensitive nerves to induce bronchial contraction in part. To confirm the mediators that cause the release of the tachykinin-like substances from the bronchus, we also examined whether phosphoramidon potentiates the effect of leukotriene C4 (LTC4), serotonin, histamine, and platelet-activating factor on bronchial contraction. When the contractions induced by these agonists reached a plateau and began to relax, we added phosphoramidon. Phosphoramidon inhibited the relaxation and significantly potentiated the contractile response to 10(-5) M LTC4, and it significantly reduced the relaxing rate of the 10(-6) M serotonin induced contraction. However, it did not change the effect of histamine and platelet-activating factor.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1892305 TI - Antigen-provoked increase in histamine reactivity. Observations on mechanisms. AB - To investigate the effect of antigen provocation on nonspecific reactivity to histamine, nine allergic individuals underwent multiple nasal challenges with histamine, or antigen. The response to challenge was assessed by counting the number of sneezes and measuring the levels of albumin and TAME-esterase (TAME; [3H]N-alpha-tosyl-L-arginine methyl ester) activity in recovered nasal lavages. In the case of antigen, levels of histamine were also measured. In response to histamine, the subjects sneezed and had increased levels of albumin and TAME. The responses to antigen or histamine were unchanged 24 h after histamine provocation. The responses to histamine provocations were increased with respect to symptom scores and to the levels of TAME activity and albumin in nasal lavages compared to baseline challenge, however, 24 h after antigen provocation. Increasing antigen exposure from 1 to 3 days did not further increase the responsiveness to histamine. Histamine reactivity returned to baseline 12 days after antigen exposure. The number of eosinophils, neutrophils, and alcian blue positive cells in the lavages after antigen challenge and before the histamine challenges correlated with the changes in response to histamine. The increase in sneezing induced by antigen stimulation correlated with the increase in the same parameter after histamine provocation 24 hr after antigen challenge (r = 0.88; p less than 0.01). Surprisingly, the other parameters assessed did not show similar correlations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1892306 TI - Intersubject variability in particle deposition does not explain variability in responsiveness to methacholine. AB - How variable is the deposition of inhaled methacholine (MCH) in the respiratory tract during a challenge test? Does this variability contribute to the variability of airway responsiveness? To examine these questions we estimated the deposition of polydisperse MCH droplets by measuring the deposition of surrogate diethylhexyl sebacate (DEHS) droplets that were similar in size (1.5 microns) but monodisperse. Light scattering photometry and flow measurements were used to compute inspired and expired DEHS particle number. Deposition of DEHS during 4 breaths was measured twice at baseline and after every dose of MCH during an abbreviated challenge test in 16 subjects. Deposition was then compared with reactivity. Reactivity to MCH was expressed as the dose-response slope; it was calculated as percent final change in FEV1/cumulative dose MCH inhaled. Dose response slopes ranged from zero (nonreactive) to -15.0 (very reactive) %/mumol (mean -3.2 +/- 5.3 SD). Seven subjects had a 20% or greater decrement in FEV1 after their highest MCH dose. Baseline DEHS deposition, which ranged from 66 to 84% (mean 77 +/- 5 SD), was not significantly different between responders and nonresponders and was not a significant predictor of the dose-response slope. Reactivity was significantly associated with an increase in deposition produced by MCH (p less than 0.007). This increase was small, however (relative change less than 7%), so that the effect on the deposited dose of MCH was minimal. We conclude that, with the breathing pattern used, individual differences in DEHS (and MCH) deposition were small and contributed little to intersubject variability of responsiveness to inhaled MCH. PMID- 1892307 TI - Lung function in school-age children who had mild lower respiratory illnesses in early childhood. AB - We examined the relationship between patterns of mild lower respiratory illness (LRI) experienced in early childhood and lung function in 89 boys and 70 girls 6 to 18 yr of age. The children's histories of outpatient visits for wheezing and nonwheezing LRI during the first 6 yr of life had been documented by physicians in a single pediatric practice. Most children were reported by their parents to have been free of recurrent respiratory symptoms during the 2 yr prior to lung function testing. In sex-specific analyses, average lung function assessed by spirometry was similar in children who had made zero or one physician visit for wheezing LRI during the preschool years. Boys who had experienced two or more episodes of wheezing LRI during the preschool years had lower average FEV1, FEV1/FVC, FEF25-75, Vmax50, and Vmax75 than did boys who had zero or one preschool wheezing illness. The association between recurrent preschool wheezing LRI and later lung function remained after exclusion of data from seven boys who were reported to have wheezed in the 2 yr prior to study. Girls who had experienced two or more preschool wheezing LRI had lower average FEF25-75 and Vmax50 than girls with a history of zero or one such illness, but differences were not statistically significant. Recurrent nonwheezing LRI during the preschool years was not significantly associated with subsequent lung function in either sex, regardless of preschool wheezing LRI history. Detailed information concerning early childhood LRI experience is valuable in epidemiologic studies of factors influencing lung function in children. PMID- 1892308 TI - Relation of dose-response slope to respiratory symptoms in a population of Australian schoolchildren. AB - To describe bronchial responsiveness in populations, the dose-response slope (DRS), which is the linear slope of the dose-response curve, may be a more useful measure of severity than the provoking dose that causes a 20% fall in FEV1 (PD20 FEV1). To examine the distribution of DRS measurements and their relation to respiratory symptoms in children, we have analyzed data collected during a population study designed to measure the prevalence of bronchial hyper responsiveness and respiratory symptoms. In this study, respiratory symptom history was measured by a self-administered questionnaire to parents and bronchial responsiveness was measured using the rapid inhalation method. Of 1,217 children studied, DRS values were obtained for 1,203 children who had technically satisfactory bronchial challenge data. In asymptomatic children, DRS values were distributed symmetrically on a logarithmic scale. The geometric mean DRS was reliable measure of the central position of the curve, and 1.96 standard deviations only slightly underestimated the 95% interval. In children with recent wheeze, the distribution was skewed toward larger DRS values. Mean DRS values were significantly different between groups determined according to symptom frequency. It appears that DRS values are more useful than PD20 FEV1 values in epidemiologic studies of respiratory illness in children because a value that relates well to symptom history can be calculated for the entire sample. The major advantages are that the measurement more clearly discriminates between symptom severity groups and that a value that represents abnormal responsiveness can be calculated. PMID- 1892309 TI - Respiratory health and PM10 pollution. A daily time series analysis. AB - This study evaluated changes in respiratory health associated with daily changes in fine particulate pollution (PM10). Participants included a relatively healthy school-based sample of fourth and fifth grade elementary students, and a sample of patients with asthma 8 to 72 yr of age. Elevated PM10 pollution levels of 150 micrograms/m3 were associated with an approximately 3 to 6% decline in lung function as measured by peak expiratory flow (PEF). Current day and daily lagged associations between PM10 levels and PEF were observed. Elevated levels of PM10 pollution also were associated with increases in reported symptoms of respiratory disease and use of asthma medication. Associations between compromised respiratory health and elevated PM10 pollution were observed even when PM10 levels were well below the 24-h national ambient air quality standard of 150 micrograms/m3. Associations between elevated PM10 levels, reductions in PEF, and increases in symptoms of respiratory disease and asthma medication use remained statistically significant even when the only pollution episode that exceeded the standard was excluded. Concurrent measurements indicated that little or no strong particle acidity was present. PMID- 1892310 TI - Exposure-related declines in the lung function of cotton textile workers. Relationship to current workplace standards. AB - To evaluate the effectiveness of the current workplace standards in preventing chronic health effects from cotton dust exposure, a 5-yr longitudinal study of a large multimill population of cotton textile and synthetic process workers, employed at a major U.S. textile company, was conducted. To control for and assess the effect of type of work area on annual change in lung function, we limited the analysis to those 1,817 subjects who, throughout their textile work history at the company, worked exclusively in cotton yarn manufacturing or slashing and weaving, or in synthetic textile mills. The expected effect of smoking on average annual change in lung function was demonstrated for both cotton and synthetic workers. Despite lower overall dust exposure, cotton yarn workers exhibited steeper annual declines in lung function than did workers in slashing and weaving; this difference persisted within each smoking category, indicating a dust potency effect. There were mill differences in annual change in lung function among cotton workers, potentially masking an exposure effect. A smoking-work area interaction persisted after adjusting for mill differences, with the largest annual declines observed in cotton yarn workers who smoke. A significant dose-response relationship was seen in cotton yarn manufacturing between annual declines in FEV1, FVC, and FEF25-75 and average exposure by mill, and the larger declines were found in mills using the highest percentage and lowest grade of cotton. Synthetic textile workers had larger declines than did cotton textile workers, which were not explained by smoking or duration of employment. Unrecognized and unmeasured causative exposures or selection bias could explain this result.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1892311 TI - The clinical utility and reliability of asbestos bodies in bronchoalveolar fluid. AB - Although asbestos bodies are easily identified in bronchoalveolar lavage (BAL) fluid and are thought to be strongly associated with the asbestos body burden in the lung parenchyma, the clinical utility and reliability of this biologic measure of exposure has not been sufficiently studied. To assess the clinical relevance of BAL asbestos bodies we compared this bioassay of exposure to other measures of exposure and also indices of lung disease in asbestos-exposed workers (n = 71). The median concentration of asbestos bodies was 0.8 bodies per ml of BAL fluid (range 0 to 34.3). Seven workers or 9.9% had zero asbestos bodies identified in the BAL fluid. The concentration of BAL asbestos bodies was not associated with the duration of exposure (r = -0.02), the time from first exposure to asbestos (r = 0.12), or the time since last exposure to asbestos (r = 0.05). Moreover, radiographic and physiologic measures of asbestos-induced lung disease were not found to be associated with the concentration of BAL asbestos bodies. In fact, of the seven study subjects with zero BAL asbestos bodies, the mean duration of exposure was 32 yr, and six of these subjects had radiographic evidence of asbestos-induced lung disease. To assess the reliability of measuring BAL asbestos bodies, we performed a second bronchoscopy on 54 subjects and directly compared the concentration of BAL asbestos bodies from both the first and second BAL samples. Within these 54 subjects, the concentration of BAL asbestos bodies was found to be a very reliable measure (r = 0.76; p = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1892313 TI - Computed tomography scan in the early detection of silicosis. AB - We evaluated the ability of both the conventional and high resolution computed tomography (CCT and HRCT, respectively) scans of the thorax to detect early silicosis in subjects exposed to silica dust in the mines and foundries of Quebec for an average of 29 +/- 2 yr. The study was limited to subjects with chest radiograph (CR) of the International Labor Organization (ILO) Categories 0 or 1 as determined independently a priori. All subjects had a standard high kilovoltage posteroanterior and lateral CR, a set of 10 to 15 1 cm collimation CCT scans, and a set of three to five 2 mm collimation HRCT scans in the upper, middle, and lower lung fields. For each CR and sets of CT scans, readings were done independently by four experienced readers. For small opacities of the lung parenchyma on CR, 32 of the 51 subjects were normal (Group A), six were indeterminate (Group B), and 13 were abnormal (Group C). By the combined readings of HRCT and CCT, 13 of the subjects (40%) in Group A were abnormal (p less than 0.001); four of the subjects in Group B were abnormal, and in Group C, one subject was normal, one indeterminate, and 11 (84%) abnormal. For confluence of small opacities, 48 of the 51 subjects were negative (Group 0), and three were positive (Group 1) on the CR. By the CT scan, 42 of the 48 subjects in Group 0 were negative, and the three subjects in Group 1 were positive; thus the CT scan added six positive cases with confluence of small opacities (six of 48, 12.5%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1892312 TI - Idiopathic pulmonary fibrosis in asbestos-exposed workers. AB - Diffuse interstitial lung disease in asbestos-exposed workers is presumed to represent asbestosis. Among 176 asbestos-exposed persons for whom lung tissue was available, we found nine with clinical features consistent with asbestosis, but histologic sections failed to demonstrate asbestos bodies, the usual requirement for pathologic diagnosis of asbestosis (Group I). These nine were compared by analytic electron microscopy with nine persons with idiopathic pulmonary fibrosis (Group II), and with nine persons with all the criteria of asbestosis (Group III). The three groups did not differ significantly with respect to lung burden of chrysotile or tremolite and actinolite, but Group III had a lung burden of amosite and crocidolite that was three orders of magnitude greater than in Groups I and II, with no overlap. We conclude that (1) the American Thoracic Society criterion of "a reliable history of exposure" is sometimes difficult to define; (2) asbestos bodies are seen in tissue sections only when exposure has been reasonably high, and given the proper clinical setting, the presence of diffuse fibrosis and asbestos bodies in tissue sections are sensitive and specific criteria for a diagnosis of asbestosis; and (3) the prevalence here of 5.1% nonasbestos-induced interstitial lung disease among asbestos-exposed persons is artefactually high because of atypical case selection. However, because asbestosis is a disappearing disease, such cases will become more frequent. The identification of these other diseases is important because therapy and prognosis may differ from that of asbestosis. PMID- 1892314 TI - Structural features of interstitial lung disease in systemic sclerosis. AB - Most studies of lung histology in systemic sclerosis have been based on autopsy specimens and consequently emphasize end-stage fibrotic disease. Although occasional pathologic descriptions of open-lung biopsies have recognized the presence of inflammatory cells, suggesting a similarity to "lone" cryptogenic fibrosing alveolitis, the two conditions have never been formally compared. In this study we describe the morphologic features of 49 open-lung biopsies from 34 systemic sclerosis patients with interstitial lung disease, many of whom had their lung disease diagnosed at an early stage. None had pulmonary hypertension. Examination of lung tissue by light microscopy showed the earliest changes to include patchy lymphocyte and plasma cell infiltration of the alveolar walls, interstitial fibrosis, and increased macrophages but only occasional polymorphonuclear cells and lymphocytes in the alveolar spaces. Alveolitis was not observed without fibrosis. Comparison of 22 biopsies with a similar number from patients with lone cryptogenic fibrosing alveolitis, matched for age and sex, revealed no qualitative or quantitative differences, other than a higher prevalence of focal lymphoid hyperplasia (follicular bronchiolitis) in the systemic sclerosis patients than in the lone cryptogenic fibrosing alveolitis controls (23 and 5%, respectively). There was an inverse correlation between the extent of interstitial inflammation and patients' age (p less than 0.05), disease duration (p less than 0.05), and age at onset of systemic sclerosis (p less than 0.01). There was also an inverse correlation between DLCO and interstitial fibrosis (p less than 0.01) and loss of lung architecture (p less than 0.05). Ultrastructural studies of eight systemic sclerosis biopsies showed evidence of endothelial and epithelial injury together with interstitial edema and excess collagen deposition. Occasional mast cells were observed, often in close contact with interstitial fibroblasts, but there were no tubuloreticular structures or evidence of immune complexes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1892315 TI - Mica-associated pulmonary interstitial fibrosis. AB - We present the clinical and biopsy findings of a 63-yr-old white male with interstitial pulmonary fibrosis and a long history of extensive exposure to mica while working in the rubber industry. The patient presented 30 yr after the initial exposure with complaints of progressive shortness of breath and a chronic nonproductive cough. Pulmonary function testing revealed restrictive lung function with a mild reduction in the total lung capacity (80% of predicted) and a moderate-to-severe reduction in the diffusing capacity of carbon monoxide (50% of predicted). The chest radiogram and high-resolution chest CT scan showed diffuse fibrosis and focal honeycombing involving the upper and lower lung zones bilaterally. Bronchoalveolar lavage revealed 20% neutrophils in the lavage fluid with abundant rectangular flaking crystals. Open-lung biopsy exhibited extensive fibrosis and architectural remodeling with abundant sheets and fragments of engulfed polarizable crystalline material. Energy-dispersive spectroscopy and electron diffraction studies confirmed the material to have the features of mica. Asbestos and other silicates were not identified. The documentation of prolonged exposure to mica, the clinical and radiographic features of severe interstitial fibrosis, and the histopathologic delineation of the interstitial lesion, including spectroscopic and crystallographic verification of crystalline mica, support the causal relationship between mica and interstitial fibrosis. PMID- 1892316 TI - Methacholine airway responsiveness and 24-hour urine excretion of sodium and potassium. The Normative Aging Study. AB - Prior studies have suggested a direct relationship between dietary sodium intake and nonspecific airway responsiveness. The relationship of dietary sodium and potassium intake to methacholine airway responsiveness was examined among 273 male participants of the Normative Aging Study (age range 44 to 82 yr) using 24-h urinary excretion of these cations as a surrogate for intake. Methacholine airway responsiveness was analyzed as dose-response slope, a continuous measure of responsiveness that represents the slope of a line connecting the origin to the last point of the dose-response plot. Greater airway responsiveness to methacholine was associated with greater potassium excretion. A significant relationship between methacholine dose-response slope and potassium excretion (p = 0.014) was observed in multivariate analysis that took into account other covariates, including age, percentage of predicted FEV1, cigarette smoking, and skin test reactivity. In contrast, methacholine airway responsiveness did not appear related to urinary sodium excretion. These data suggest that dietary potassium may have an influence on airway responsiveness of middle-aged and older men. PMID- 1892317 TI - Withholding and withdrawing life-sustaining therapy. This Official Statement of the American Thoracic Society was adopted by the ATS Board of Directors, March 1991. PMID- 1892318 TI - Airway mucin. Sixth Transatlantic Airway Conference. Key Biscayne, Florida, January 1991. Proceedings. PMID- 1892319 TI - The structure of human intestinal apomucins. AB - Human intestinal mucins are large glycoconjugates (greater than 1,000,000 D) that coat the epithelium, serving to lubricate and protect. Apart from this physiologic function, mucins are important in that they are frequently altered in cancer; thus, they have potential usefulness as tumor markers. We have isolated mucins from human LS174T colon cancer cells and small intestine, deglycosylated these highly purified glycoconjugates, produced polyclonal antibodies to the apomucins, and used these antibodies to isolate two different types of cDNA clones that encode different apomucins. The first class of cDNA clones was isolated using antibodies to deglycosylated LS174T mucin. These cDNA, designated SMUC or MUC2, contain 69 nucleotide tandem repeats that encode a repetitive peptide that is extremely rich in threonine and proline. Northern blots using MUC2 cDNA as probes exhibit large (7,600 bases) and polydisperse hybridization bands. This gene is polymorphic within the human population and is located on chromosome 11. The second class of cDNA was isolated using antibodies to deglycosylated small intestinal mucin. These cDNA, designated SIB or MUC3, have 51 nucleotide tandem repeats that encode a threonine- and serine-rich repetitive peptide. This mucin also is encoded by a large, polydisperse message, but it is clearly distinct from MUC2 as it is located on chromosome 7. Both the MUC2 and MUC3 mucins are expressed in colonic tumors; however, the level of their expression is quite variable. Thus, at least two mucins are expressed by the human gastrointestinal tract. Elucidation of the regulation of these two genes will be important in understanding the physiology and pathophysiology of the human intestine. PMID- 1892320 TI - Structural features of the core proteins of human airway mucins ascertained by cDNA cloning. AB - Tracheobronchial secretions are one of the most important elements of the mucociliary system that protects the respiratory mucosa. They contain bronchial mucus, which is composed of a group of macromolecules secreted by the goblet cells of the epithelium and the submucosal glands. Bronchial mucins are the most characteristic molecules of this mucus. They form a group of complex, polydispersed O-linked glycoproteins containing sugars, which make up 80% of their weight. The protein core of human airway mucin has been difficult to sequence by traditional technologies because of its high content of serine and threonine residues linked to numerous oligosaccharide chains. We therefore prepared a lambda gt11 cDNA library from one sample of human tracheobronchial mucosa and screened this library with a polyclonal antibody directed against the apopeptides of human bronchial mucins. We obtained 20 positive clones that were sequenced. These sequences were classified into three different types. The use of the nucleotide probes from these clones in Northern blot analysis showed that the RNA messages were extremely polydispersed. At the current time, four of these probes allow us to map human tracheobronchial mucins genes to at least three different chromosomes. These results suggest that the peptide moiety of the human airway mucin is very heterogeneous. PMID- 1892321 TI - The carbohydrate diversity of human respiratory mucins: a protection of the underlying mucosa? AB - Human respiratory mucins consist of a family of glycoproteins with different peptides in which glycosylation, the major post-translational phenomenon, is responsible for about 70 to 80% of the weight of these molecules. This glycosylation generates a remarkable diversity of O-glycosidically linked carbohydrate chains, which are expressed as several hundreds of different chains in a single person. These chains, which can vary from one to about 20 sugars, may be neutral, sialylated, or sulfated. They bear multiple epitopes. Some antigenic determinants such as ABO, Leb antigens in secretor individuals, Lea, or X or Y antigens have been identified. There is increasing evidence that, among other functions, this diversity of chains allows many interactions with microorganisms and may be an important factor in maintaining the sterility of the respiratory tree. In certain pathologic situations such as cystic fibrosis, which is associated with colonization by Pseudomonas aeruginosa, the hypothesis of an alteration of this interaction is open. PMID- 1892322 TI - Glycoprotein synthesis and secretion: translation and targeting. AB - To establish and maintain organelle identity, the eucaryotic cell must be able to target newly synthesized proteins to the various cellular compartments. The specificity of this process appears to be generally mediated by the interaction of structural features of the transported proteins (sorting signals) with cellular proteins that bind these structures and mediate the targeted transport (sorting receptors). Although signals involved in the sorting into a variety of intracellular organelles as well as some (putative) receptor proteins have been identified, the sorting signals and receptors involved in the targeted transport of proteins to the cells surface are just beginning to evolve. PMID- 1892323 TI - Mucin exocytosis. AB - Mucins produced by goblet cells of the respiratory mucosa are condensed while stored in secretory granules. Mucin condensation and its decondensation upon exocytosis can be explained by the theory of polymer gel phase transition. After the opening of a secretory pore, Ca2+ inside the granule is exchanged for extracellular Na+. Na/Ca exchange triggers a polymer gel phase transition whereby the mucin polymer matrix undergoes massive swelling and thereby changes from a condensed to a hydrated phase. Swelling of the granular content is driven by a Donnan potential and results in the release of secretory product and the formation of small mucin gels, which later anneal to each other to form the respiratory mucus. Because of the tangled rather than cross-linked topology of the mucin network, the rheologic properties of the respiratory mucus depend primarily on hydration. As mucins are polyionic, the hydration of mucus is controlled by a Donnan equilibrium. Hence, mucus hydration and rheology are determined by two factors: the quantity, chain length, and charge density of the secreted mucins, and the amount and the ionic and polyionic composition of the water transported across the respiratory mucosa. PMID- 1892324 TI - Mucin in disease. Modification of mucin gene expression in airway disease. AB - Mucus hypersecretion is a characteristic feature of several human airway diseases, including chronic bronchitis, cystic fibrosis, and asthma. Although its pathogenesis is poorly understood, hypersecretion apparently results from the abnormally large number of mucous cells found in hypersecretory airways. The factors giving rise to these mucous cells are unknown, but experimental evidence supports possible roles for both mitosis (mucous cell hyperplasia) and differentiation (mucous cell metaplasia). On the basis of the hypothesis that differentiation would require activation of mucin mRNA transcription, we have used mucin cDNA to monitor mucin mRNA levels in an animal model of chronic bronchitis. We first showed that a mucin gene (SMUC or MUC-2) cloned from the human intestine is also expressed in the human airways and is the same or homologous to genes expressed in other human mucin-producing organs. We next showed that a homologue of the SMUC gene is expressed in several animal species, including the rat. Finally, we showed that the induction of experimental chronic bronchitis by SO2 in rats is accompanied by the induction (from near zero baseline) of airway mucin mRNA. The induction by irritants of high steady-state levels of mucin mRNA may represent one of the early events in mucous cell differentiation and hypersecretion. PMID- 1892325 TI - Mucin structure. The structure and heterogeneity of respiratory mucus glycoproteins. AB - Respiratory mucus glycoproteins purified from both "normal" respiratory secretions and sputa of patients with a variety of hypersecretory conditions are high Mr linear molecules adopting a random coil configuration in solution. Studies on their polydispersity show them to have an Mr in the range 3 to 32 x 10(6) and a distribution of length from 200 nm to beyond 10 microns. These macromolecules are fragmented by reduction of intermolecular disulfide bonds into subunits, with Mr approximately 2 x 10(6) and length from 200 to 600 nm. Reduction not only cleaves the mucin molecule but opens, presumably by breaking intramolecular disulfide bonds, cryptic "naked" protein regions. Trypsin digestion of subunits yields high Mr glycopeptides (Mr, 300 to 500,000), presumably by cleavage of the peptide core within the unfolded "naked" protein domains. Respiratory mucus glycoproteins from infected sputum samples are usually heterogeneous in CsCl density gradients, in contrast to those from "normal" tracheobronchial secretions. The former are characterized by the presence of a number of different mucin species, and the basis for the separation of these mucins appears to be the variable presence of sialic acid and sulfate moieties in the oligosaccharide clusters. This heterogeneity may reflect a difference in cellular origin of the mucins and also may be clinically significant. PMID- 1892326 TI - Structure and biology of a carcinoma-associated mucin, MUC1. AB - Although mucins have been studied at the biochemical and biophysical level for some time, attempts to define their structures in detail were only partially successful because of their size and complexity. The advent of monoclonal antibodies reactive with these molecules introduced a new approach to structural studies by defining antigenic epitopes, by allowing purification of the mucin molecules by affinity chromatography, and by providing a means to clone genes coding for the core proteins. By their profile of reactivity with the normal and cancer-associated mucin in a particular tissue, the antibodies also defined a difference in the mucin derived from the two sources. It is now clear that this difference lies in the carbohydrate side chains, as the core proteins are identical. Because the mucins are tumor-associated antigens and the cancer mucins can express epitopes that are relatively tumor specific, this family of molecules is now being intensively studied. There is also considerable interest in elucidating the normal function of the mucin and in determining whether, through an altered structure, this function is subverted in malignancy. In the next few years we should expect that the structure of other mucins will be defined in the same detail as the product of the MUC1 gene. We should also expect to see the continued application of mucin-reactive antibodies in the clinic and the investigation of mucins as agents for immunotherapy of some cancers. As to the function(s) of these molecules, perhaps we will learn enough in the future to make a critical reappraisal of the name. PMID- 1892327 TI - Role of mast cell and neutrophil proteases in airway secretion. AB - To investigate the hypothesis that mast cell and neutrophil proteases stimulate airway gland secretion, we studied the effects of two mast cell proteases (tryptase and chymase) and two neutrophil enzymes (human neutrophil elastase and cathepsin G) on secretion of 35S-labeled macro-molecules from cultured bovine airway gland serous cells. Tryptase had no effect, but the other three enzymes stimulated secretion. Threshold concentrations of the enzymes (greater than or equal to 10(-10) M) were lower by two orders of magnitude than other agonists (e.g., histamine, prostaglandins, beta-adrenergic agonists). Only proteases induced maximal secretory response (greater than or equal to 80% depletion of 35S labeled macromolecules), and these responses were greater than 10-fold larger than those of other agonists. The active catalytic sites of the enzymes are required for their secretory activities. These findings suggest a role for these enzymes in the pathogenesis of inflammatory airway diseases associated with hypersecretion, and they suggest that the use of selective site-directed inhibitors of these enzymes may provide a novel strategy for intervention in inflammatory diseases of the airways associated with hypersecretion (e.g., cystic fibrosis, chronic bronchitis). PMID- 1892328 TI - Human nasal respiratory secretions and host defense. AB - The largest human body surface is the lining of the respiratory tract, gastrointestinal tract, and reproductive system each of which is covered by mucous membranes, named for their capacity to secrete mucus. Recent studies of mucus have defined some of the physiologic and pharmacologic controls of secretions. However, the constituents that are found in mucus and their roles in human health and disease are still in the initial phases of exploration. Human nasal respiratory secretions provide one convenient source of mucous membrane secretions. Nasal secretions include a variety of proteins, which appear to serve important functions in host-defense. Most, if not all, of the antiphlogistic products are synthesized and secreted by serous cells in the submucous glands, and it appears that the serous cell is the resident antimicrobial cell in mucous membranes. PMID- 1892330 TI - Physician practices in the prevention of venous thromboembolism. AB - OBJECTIVE: To determine the rate of use of prophylaxis for venous thromboembolism in high-risk hospital patients. DESIGN: A retrospective medical record review. SETTING: A community-wide study in 16 short-stay hospitals in central Massachusetts. PATIENTS: A total of 2017 patients with multiple risk factors for venous thromboembolism. MEASUREMENTS AND MAIN RESULTS: On the basis of age, length of hospitalization, and the presence of at least one additional major risk factor, 17% of 151,349 discharges (25,410 patients) were identified as being at high risk for venous thromboembolism. Eight percent of these discharges were randomly selected for medical record review. Prophylaxis for venous thromboembolism was received by 32% of these high-risk patients. Prophylaxis use among the 16 study hospitals varied widely, ranging from 9% to 56%, and was higher in teaching hospitals than in nonteaching hospitals (44% compared with 19%; P less than 0.001). One or more of the following methods of prophylaxis was used: low-dose heparin (78%), intermittent calf compression (13%), warfarin (12%), and inferior vena caval filter (3%). Use of prophylaxis increased with the number of risk factors identified (P less than 0.001). CONCLUSION: Prophylaxis for venous thromboemobolism is underused, particularly in nonteaching hospitals. PMID- 1892329 TI - Enterobacter bacteremia: clinical features and emergence of antibiotic resistance during therapy. AB - OBJECTIVES: To study the effect of previously administered antibiotics on the antibiotic susceptibility profile of Enterobacter, the factors affecting mortality, and the emergence of antibiotic resistance during therapy for Enterobacter bacteremia. DESIGN: Prospective, observational study of consecutive patients with Enterobacter bacteremia. SETTING: Three university tertiary care centers, one major university-affiliated hospital, and two university-affiliated Veterans Affairs medical centers. PATIENTS: A total of 129 adult patients were studied. MEASUREMENTS: The two main end points were emergence of resistance during antibiotic therapy and death. MAIN RESULTS: Previous administration of third-generation cephalosporins was more likely to be associated with multiresistant Enterobacter isolates in an initial, positive blood culture (22 of 32, 69%) than was administration of antibiotics that did not include a third generation cephalosporin (14 of 71, 20%; P less than 0.001). Isolation of multiresistant Enterobacter sp. in the initial blood culture was associated with a higher mortality rate (12 of 37, 32%) than was isolation of a more sensitive Enterobacter sp. (14 of 92, 15%; P = 0.03). Emergence of resistance to third generation cephalosporin therapy (6 of 31, 19%) occurred more often than did emergence of resistance to aminoglycoside (1 of 89, 0.01%; P = 0.001) or other beta-lactam (0 of 50; P = 0.002) therapy. CONCLUSIONS: More judicious use of third-generation cephalosporins may decrease the incidence of nosocomial multiresistant Enterobacter spp., which in turn may result in a lower mortality for Enterobacter bacteremia. When Enterobacter organisms are isolated from blood, it may be prudent to avoid third-generation cephalosporin therapy regardless of in-vitro susceptibility. PMID- 1892331 TI - Clinical genetics and genetic counseling in Alzheimer disease. AB - Because of growing evidence for genetic causes of Alzheimer disease, clinicians are often asked about risks for this disorder among relatives of patients. This paper briefly reviews the evidence for genetic and other causes of Alzheimer disease, including specifically its typical late-onset variant. Several recent developments in the molecular genetics of early-onset Alzheimer disease are described briefly. These findings, however, may not apply to more typical, late onset Alzheimer disease. Genetic studies of the latter disorder are complicated by the censorship of any inherited predisposition to disease by death from other causes. Hence, heritable disease may be apparent only in families with large numbers of elderly relatives at risk. Relying on empiric observations of risk among relatives from several recent studies of pooled Alzheimer families, curves are presented describing theoretic age-specific risks in relatives of patients and unaffected controls. Real (current) lifetime risks of Alzheimer disease are then estimated by modification of the theoretic figures with corresponding current age-specific mortality characteristics of the U.S. population. The lifetime incidence among relatives of patients with Alzheimer disease is estimated to be 19%, or three to four times the risk among control relatives. Because both mortality of and risk for Alzheimer disease change rapidly with advancing age, it may be possible to reduce the current morbidity from Alzheimer disease by 50% if onset can be postponed by only 5 years. PMID- 1892332 TI - Ventricular late potentials in myotonic dystrophy. AB - OBJECTIVE: To determine the prevalence of ventricular late potentials, as determined by signal-averaged electrocardiography, in patients with myotonic dystrophy. DESIGN: Cross sectional, with blinded analysis of all electrocardiographic data. SETTING: Outpatient departments of a Veterans Affairs medical center and a tertiary care private hospital. PARTICIPANTS: Twenty-four patients with myotonic dystrophy. Patients were excluded from the study if they had either a history suggestive of significant ventricular arrhythmias or electrocardiographic evidence of a bundle-branch block. Two comparison groups were also formed; one group included 44 healthy employees at the tertiary hospital and the other, 30 cardiac patients with inducible ventricular tachycardia. MAIN RESULTS: A time-domain analysis of the signal-averaged electrocardiograms showed that 75% of patients with myotonic dystrophy met one criterion for the presence of late potentials, 67% met two criteria, and 29% met all three criteria. Spectrotemporal mapping in these patients showed markedly abnormal spectral peaks with a mean factor of normality that was significantly lower than that of the normal volunteers; the frequency of electrocardiographic abnormalities approached that seen in patients with known ventricular tachycardia. The presence of late potentials correlated directly with the length of the PR interval and inversely with left ventricular fractional shortening. CONCLUSIONS: In our study, the prevalence of late potentials on signal-averaged electrocardiography in patients with myotonic dystrophy approached that seen in cardiac patients with inducible ventricular tachycardia. It is possible that ventricular arrhythmias play a role in the occurrence of sudden death in some patients with myotonic dystrophy. PMID- 1892333 TI - Chronic renal failure in sickle cell disease: risk factors, clinical course, and mortality. AB - OBJECTIVE: To determine the incidence, clinical course, and risk factors associated with the onset of chronic renal failure in sickle cell anemia and sickle C disease. DESIGN: A prospective, 25-year longitudinal demographic and clinical cohort study. A matched case-control study was conducted to determine risk factors. PATIENTS: A total of 725 patients with sickle cell anemia and 209 patients with sickle C disease who received medical care from the hematology service in a large municipal hospital. Most were observed from birth or early childhood. MEASUREMENTS: Thirty-six patients developed sickle renal failure: 4.2% of patients with sickle cell anemia and 2.4% of patients with sickle C disease. The median age of disease onset for these patients was 23.1 and 49.9 years, respectively. Survival time for patients with sickle cell anemia after the diagnosis of sickle renal failure, despite dialysis, was 4 years, and the median age at the time of death was 27 years. Relative risk for mortality was 1.42 (95% Cl, 1.12 to 1.81; P = 0.02) compared with patients who did not develop renal insufficiency. MAIN RESULTS: Histopathologic studies showed characteristic lesions of glomerular "drop out" and glomerulosclerosis. Case-control analysis showed that ineffective erythropoiesis with increasingly severe anemia, hypertension, proteinuria, the nephrotic syndrome, and microscopic hematuria were significant pre-azotemic predictors of chronic renal failure. The risk for sickle renal failure was increased in patients who had inherited the Central African Republic beta s-gene cluster haplotype. CONCLUSIONS: The pre-azotemic manifestations of hypertension, proteinuria, and increasingly severe anemia predict end-stage renal failure in patients with sickle cell disease. The rate of progression of renal insufficiency is genetically determined. Treatment of the uremic phase has been dismal, underscoring the need for the development of useful pre-azotemic therapeutic modalities. PMID- 1892334 TI - Disseminated intravascular coagulation after factor IX complex resolved using purified factor IX concentrate. PMID- 1892335 TI - The Patient Self-Determination Act and the future of advance directives. AB - Living wills and other advance directives currently play a limited role in medical decision making. A new federal law, the Patient Self-Determination Act, will require health care providers in hospitals, nursing homes, and other facilities to inquire about the presence of advance directives, to record patient preferences in the medical record, and to develop institutional policies regarding the implementation of these directives. Unfortunately, the law does little to promote discussion or preparation of advance directives before hospitalization. Additional efforts to promote the use of advance directives can take place in the outpatient medical care system, in attorneys' offices, or through health insurers. Because most people have not yet prepared an advance directive, we suggest that institutions develop treatment policies for situations in which the wishes of patients who lack decisional capacity are not known. These policies should be designed to promote the patients' best interests, as defined by the consensus of the institutions' staff and members of the surrounding community. PMID- 1892336 TI - New beta-lactams: new problems for the internist. PMID- 1892337 TI - Barriers to treating obesity. PMID- 1892338 TI - Dementia screening. PMID- 1892339 TI - Levothyroxine-cholestyramine interaction reemphasized. PMID- 1892340 TI - Cigarette smoking and facial wrinkling. PMID- 1892341 TI - Renal insufficiency and secondary hyperparathyroidism in elderly patients. AB - Glomerular filtration rate (GFR) is frequently reduced in elderly people. However, the effect of this on mineral metabolism in this population has received little attention. GFR, serum intact parathyroid hormone (PTH) and vitamin D metabolites were measured in 37 patients admitted to hospital for various reasons. In 20 patients with GFR greater than 50 mL/min, an elevated serum intact PTH concentration (greater than 5.4 pmol/L) was found in two, while in 17 patients with GFR less than 50 mL/min PTH was elevated in 13. One of this group was hypercalcaemic and presumed to have primary hyperparathyrodism. Adjusted calcium was normal in all other patients. Two patients had a low serum 25 hydroxyvitamin D concentration (less than 9 nmol/L) suggesting vitamin D insufficiency while a further five had a reduced 1,25-dihydroxyvitamin D concentration, four of these having a GFR less than 50 mL/min. We conclude that hyperparathyrodism is common in hospitalized elderly patients, particularly in those with mild to moderate renal insufficiency. This may contribute to bone mineral loss in such patients. PMID- 1892342 TI - Post-traumatic hypothalamic-pituitary dysfunction presenting with biochemical features of primary hypothyroidism. AB - Two cases of post-traumatic hypothalamic-pituitary dysfunction are described where the primary pathology was shown to be understimulation of the pituitary by hypothalamic hormones. In each case, the biochemical presentation was a low serum thyroxine and elevated TSH concentration mimicking primary hypothyroidism. Treatment with thyroxine before cortisol replacement was not beneficial. In both cases, hydrocortisone therapy alone resulted in a rise in serum thyroxine and fall in serum TSH. Chronic cortisol deficiency may directly impair the thyroid response to TSH, whilst thyroxine appears to exert its feedback primarily at pituitary rather than hypothalamic level. PMID- 1892343 TI - The clinical utility of a non-isotopic two-step assay (DELFIA) and an analogue radioimmunoassay (SimulTRAC) for free thyroxine compared. AB - The analytical and diagnostic performance of a new non-isotopic, two-step immunoassay (DELFIA) for the measurement of free thyroxine (free T4) in plasma or serum has been compared with an established second generation analogue radioimmunoassay (SimulTRAC). Both methods had a good diagnostic specificity in pregnancy, thyroid clinic patients, and patients taking anticonvulsant drugs. In patients presenting to a general medical ward the diagnostic specificity of both methods was poor. Two samples appeared to contain substances which produced assay interference by DELFIA but not by SimulTRAC assays. When free T4 was measured by equilibrium dialysis a clear association between sample dilution and free T4 concentration was demonstrated in sick euthyroid patients. In contrast, using samples obtained from patients with known thyroid disease, free T4 was little influenced by sample dilution. The effects of sample dilution on free T4 measured by DELFIA were similar to those found using equilibrium dialysis. It would appear that free T4 measurements have a relatively poor diagnostic specificity in non thyroidal illness irrespective of the method used. PMID- 1892344 TI - Enzyme immunoassay of serum erythropoietin in healthy children: reference values. AB - A solid phase enzyme immunoassay for erythropoietin which required only a small specimen of blood was evaluated. It permitted measurement up to 150 IU/L. Recovery was between 86.2% and 110.0% and between-batch precision between 4.7% and 5.7%. We determined the levels of erythropoietin in infants aged 10 months (geometric mean 11.2 IU/L; 95% range 3.6-34.9) and in children aged 2 years (geometric mean 10.5 IU/L; 95% range 4.3-25.8). Both were significantly higher than the values found in children aged 4 years (geometric mean 7.2 IU/L; 95% range 2.4-21.8). There were no differences between the values in children at 4 years, those aged 4-15 years and adults. PMID- 1892345 TI - Safe, stable, whole blood samples for quality assessment of glucose measurement by non-laboratory staff. AB - A whole blood control material has been used to assess the analytical performance of non-laboratory staff who use glucose meters in clinical areas. It is prepared from sterile horse blood which is readily available from a commercial source. There are no known infection or disease transmission risks to users. When the material is stabilized by the addition of sodium fluoride less than 3% loss of glucose over 48 h is observed from an initial value of 10 mmol/L. However, we prefer to stipulate that the glucose is measured on the day of receipt. The material has been used successfully with Reflolux IIM meters and B-M sticks (Boehringer Mannheim, UK) for over a year in our hospital. PMID- 1892347 TI - Influence of sex and age in the risk of urolithiasis--a biochemical evaluation in Indian subjects. AB - Urinary lithogenic promoters and inhibitors were estimated in normal Indian men and women of young and old ages to understand the sex difference in the risk of stone disease. Young men displayed increased phosphate excretion and a higher mean calcium (both lithogenic promoters) and lower excretion of citrate (lithogenic inhibitor) compared to women of the same age indicating that young men are more at risk for calculous disease than women. In the older postmenopausal women, there was increased excretion of calcium and magnesium and a lower mean citrate than in the younger women suggesting that oestrogenic activity during reproductive years appears to offer protection against calculogenesis. This study indicates that sex differences exist in the excretion of lithogenic promoters and inhibitors which partly explain the difference in the incidence of urolithiasis between men and women. PMID- 1892346 TI - Screening for hyperlipidaemia in diabetes mellitus. Relationship to glycaemic control. AB - Diabetic patients have an increased risk of developing cardiovascular disease which, in part, may be due to lipid abnormalities. Our aim was to establish from an initial screening programme what proportion of diabetic patients attending a routine diabetic outpatient clinic had hyperlipidaemia despite having good or acceptable glycaemic control. We screened 299 randomly selected diabetic patients to assess the prevalence of hyperlipidaemia and its relationship to glycaemic control. Twenty-eight per cent had hyperlipidaemia (defined as cholesterol greater than 6.5 mmol/L and/or non-fasting triglycerides greater than 3 mmol/L). Of these hyperlipidaemic patients, 71% had good or acceptable glycaemic control as defined by a glycated haemoglobin value of less than 10%. Approximately 40% of type 2 diabetic patients had body mass index values outside recommended targets indicating the potential of weight reduction in this group as a treatment modality. Our results indicate that the majority of hyperlipidaemic diabetic patients had good or acceptable glycaemic control, and as such these patients are potential candidates for specific lipid lowering therapy. PMID- 1892348 TI - Purification of human pancreatic lipase and the influence of bicarbonate on lipase activity. AB - Pancreatic lipase was purified from human pancreatic juice by ion exchange chromatography and HPLC molecular sieve chromatography. The molecular weight was measured as 50 Kda by SDS-PAGE, as 47 Kda by HPLC and was calculated as 51 Kda following amino acid analysis. The isoelectric point of the purified lipase was 7.4 and maximal enzyme activity occurred at pH 9.5 in glycine buffer (0.1 mol/L) containing deoxycholate (19 mmol/L), colipase (3 mg/L) and triolein (0.3 mmol/L). However, the addition of bicarbonate at a final concentration of 0.1 mol/L decreased the pH for maximal enzyme activity and increased the lipase activity significantly. At higher concentrations of bicarbonate the lipase activity decreased. These results suggest that bicarbonate is an important regulator of lipase activity, perhaps related to an effect on the detergent properties of deoxycholate. PMID- 1892349 TI - Potential of descriptive linear discriminant analysis for studying clinical chemical and haematological data from persons with heterozygous sickle cell disease. AB - To study the potential of multivariate classification methods in order to obtain more insight into abnormal laboratory data from patients with sickle cell disease, we investigated standard haematological and clinical chemical variables of 18 controls and 37 apparently healthy persons with heterozygous sickle cell disease (Hb AS), all women, using both univariate and multivariate classification methods. In the univariate method, those with Hb AS showed decreased serum log aspartate aminotransferase (log AST) activity, mean corpuscular volume and mean corpuscular haemoglobin (MCH) and increased sodium concentration. The multivariate method identified sodium, potassium, urea, uric acid, log AST, alanine aminotransferase and MCH as the variables that produced maximal separation between persons with Hb As and controls. It increased the 'non-error rate' for classification of persons with Hb AS by 16.4% compared with classification based on the variable, MCH, that produced maximal separation by the univariate method. The frequency distribution of percentage Hb S in the Hb AS group proved bimodal with maximal separation at 37.0% Hb S. The subgroup with 37.0% or less (n = 16) was considered to have concomitant heterozygous alpha thalassaemia-2. In the univariate method the subgroup characterized by greater than 37.0% Hb S (n = 21) had increased serum sodium and uric acid concentrations, perhaps related to sickle cell nephropathy, whereas the subgroup with less than or equal to 37% Hb S did not. The multivariate method added information to the univariate method by additionally identifying abnormalities in serum potassium and urea concentrations in the former subgroup.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1892350 TI - Bhattacharya: a new application for quality control. AB - The Bhattacharya method and the 'average of normals' method for internal quality control were compared. Both are based on unselected patient test results. The Bhattacharya method is mostly used in clinical chemistry for calculation of reference intervals but could be modified for quality control procedures. Using the data of a coagulation test and stimulating systematic errors, it was concluded that the Bhattacharya method is more sensitive to expected shifts and is more flexible than the 'average of normals' method. PMID- 1892351 TI - Analytical goals for interference. AB - Objective analytical goals for interference in clinical biochemical methods have not yet been advocated. We propose that, since total analytical error is ideally less than half the within-subject biological coefficient of variation (CVI), the maximum allowable systematic error produced by an interferent (I) is: I less than CVI-(1.96 CVA + SE), where CVA is the relevant experimental analytical imprecision and SE is the systematic error. Such a goal may be applicable also to non-specificity, matrix effects and carryover. PMID- 1892352 TI - Development of a rapid latex enhanced turbidimetric assay for retinol binding protein in urine. AB - We describe a simple, rapid and sensitive homogeneous immunoassay for urinary retinol-binding protein (RBP) using latex particle-enhanced turbidimetric immunoassay. Rabbit anti-human RBP is covalently coupled to 40 nm latex particles and the assay performed on the IL Monarch 2000 centrifugal analyser, with a 20 microL sample volume and the reaction monitored at 340 nm over an 8 min period. The assay range is 0-6 mg/L with a detection limit of 25 micrograms/L. The within and between assay coefficients of variation are less than 1.5% and less than 2.5%, respectively. Comparison with radioimmunoassay for RBP showed good agreement. PMID- 1892353 TI - Comparison of a colorimetric potassium method with flame photometry and ion selective electrodes. PMID- 1892354 TI - Glycated haemoglobin measurement in uraemic patients. PMID- 1892355 TI - Normal catecholamine production in a patient with a paroxysmally secreting phaeochromocytoma. PMID- 1892356 TI - Biochemical investigation of hypertension. PMID- 1892357 TI - Boy or girl? PMID- 1892358 TI - More on the PST blood collection tubes. PMID- 1892359 TI - Medullary catecholaminergic neurons in the normal human brain and in Parkinson's disease. AB - Parkinson's disease is thought to cause degeneration of melanin-pigmented catecholaminergic neurons throughout the brainstem, but little quantitative information is available on the fate of catecholaminergic neurons associated with the dorsal vagal complex or medullary reticular formation. We therefore examined these neurons in the normal human medulla and in the brains of patients with Parkinson's disease, using both a melanin stain and immunohistochemical methods with an antiserum against tyrosine hydroxylase. The greatest numbers of catecholaminergic neurons in the ventrolateral reticular formation (A1/C1 group) were located in the far rostral medulla, whereas the largest populations of catecholaminergic cells in the dorsal vagal complex (A2/C2 group) were found at the level of the area postrema. No loss of cells was observed in the A1/C1 group in the parkinsonian brains. In contrast, the A2/C2 group showed moderate loss of neurons, most marked at the level of the area postrema. This difference was entirely due to the loss of neurons in the medial component of the A2 group, a population that normally is only lightly pigmented, while the heavily pigmented neurons in the ventral and intermediate components of the A2 complex were unaffected. Parkinson's disease causes degeneration only of selected populations of medullary catecholaminergic neurons, without apparent relationship to the extent of melanin pigmentation. PMID- 1892360 TI - Cerebrovascular abnormalities in pediatric stroke: assessment using parenchymal and angiographic magnetic resonance imaging. AB - Three-dimensional (volume) magnetic resonance angiography is a noninvasive technique that images the intracranial and cervical arterial vasculature without contrast agents. Twenty-four children with strokes had combined parenchymal magnetic resonance imaging and magnetic resonance angiography 1 day to 4 years after acute presentation. Eight had had prior intra-arterial angiography. Eighteen magnetic resonance angiographic studies showed arterial stenosis or occlusion in the vascular distribution of magnetic resonance image-defined brain infarction and, in 7 children, in the same location as previously defined abnormalities on intra-arterial angiography. One child had a normal intra arterial angiogram and magnetic resonance angiogram. The other 5 children with normal magnetic resonance angiographic studies included 3 with presumed embolic disease, 1 with meningitis, and 1 with Crohn's disease-related vasculitis. Collateral flow patterns could be determined in 4 children. Artifact presenting as filling defects in vessels was present in 10 studies, but did not interfere with interpretation of 8 studies. Combined magnetic resonance imaging/magnetic resonance angiography provides a screening technique to evaluate noninvasively brain parenchyma and vasculature in children with suspected large-vessel abnormalities, allowing selection for intra-arterial angiography and serial monitoring of vascular abnormalities over time and during therapeutic intervention. PMID- 1892361 TI - The acetylcholine-induced flare response in evaluation of small fiber dysfunction. AB - We iontophoresed acetylcholine on the dorsum of the foot and simultaneously measured flare and sweat responses using laser Doppler and sudorometric techniques, respectively. We compared these responses with those induced by histamine. Both acetylcholine and histamine produced dose-dependent flare, but only acetylcholine produced sweat responses. Responses to acetylcholine and histamine were blocked by hexamethonium chloride and pyrilamine maleate, respectively (p less than 0.01). We compared flare and sweat responses in 26 control subjects, 21 asymptomatic diabetic patients and 41 patients (17 diabetic, 24 nondiabetic) with pain symptoms suggestive of small fiber neuropathy and normal sensation (n = 15) or mild to moderate (n = 19) or severe (n = 7) sensory loss. No patient had trophic foot lesions. Basal skin blood flow and maximal flare responses were not significantly different among the various subgroups (Control subjects, 49 +/- 7.4; asymptomatic diabetic patients, 29 +/- 4; patients with small fiber neuropathy and normal sensation, 34 +/- 6; with neuropathy and mild to moderate sensory loss, 29 +/- 4.8; and with neuropathy and severe sensory loss, 35 +/- 5 ml/100 gm, for flare response, respectively). Flare responses lower than the lowest found in control subjects occurred in 5 of 21 asymptomatic diabetic patients, 4 of 15 patients with small fiber neuropathy and normal sensation, 5 of 19 with neuropathy and mild to moderate sensory loss, and 1 of 7 with neuropathy and severe sensory loss.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1892362 TI - The European Stroke Prevention Study (ESPS): results by arterial distribution. AB - The European Stroke Prevention Study was a multicenter study comparing the effect of the combination of dipyridamole, 75 mg, and acetylsalicylic acid, 330 mg, three times a day, to that of placebo in 2,500 patients in the secondary prevention of stroke or death after one or more transient ischemic attacks, reversible ischemic neurological deficits, or strokes of atherothrombotic origin. The patients with vertebrobasilar events at entry comprised one-third of the whole patient population. The overall total incidence of stroke or death (the end points) during the 2-year follow-up in the placebo group was lower in the vertebrobasilar group compared to the carotid group (14% versus 24%, respectively). The combination therapy of dipyridamole and acetylsalicylic acid caused a marked reduction in the incidence of stroke or death in patients with vertebrobasilar (51%) and carotid (30%) events. When only stroke was considered as the end point, dipyridamole and acetylsalicylic acid seemed to be more effective in reducing the risk of transient ischemic attacks than stroke, and more effective in men than in women. PMID- 1892363 TI - Strongly succinate dehydrogenase-reactive blood vessels in muscles from patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes. AB - Intramuscular blood vessels were examined with succinate dehydrogenase stain in skeletal muscle biopsy specimens from 6 patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). Almost all arteries had large granular deposits with high succinate dehydrogenase activity in their walls. Electron microscopic examination of serial frozen sections of these biopsies showed that the smooth muscle cells of the strongly succinate dehydrogenase-reactive blood vessels contained markedly proliferated mitochondria, characteristic of patients with MELAS. The presence of strongly succinate dehydrogenase-reactive blood vessels in muscle biopsy specimens provides an important clue toward understanding the underlying pathogenetic mechanism in patients with MELAS as well as another approach to the diagnosis of this disorder. PMID- 1892364 TI - Zidovudine myopathy: a distinctive disorder associated with mitochondrial dysfunction. AB - Muscle biopsy specimens were obtained from 48 human immunodeficiency virus infected patients suffering from various neuromuscular symptoms. Microscopic examination by conventional and electron microscopy revealed a characteristic structural myopathy associated with mitochondrial changes in 13 patients, all of whom had received long-term zidovudine therapy. The mean cumulative dose they had received (498 +/- 145 gm) was significantly higher than that of the other 14 zidovudine recipients of the study. They suffered from a progressive, usually painful, proximal myopathy with pronounced wasting, normal-to-moderately elevated creatine kinase levels, and a myopathic electromyographic pattern. The condition usually improved after withdrawal of the drug. Assay of mitochondrial enzymes, including succinate-cytochrome c reductase, cytochrome c oxidase, and citrate synthase, showed a decline in respiratory chain capacity. Southern blot analysis of mitochondrial DNA showed no abnormality. It is likely that mitochondrial dysfunction, probably resulting from drug-induced inhibition of the mitochondrial DNA polymerase, is implicated in the pathogenesis of this complication of zidovudine therapy. PMID- 1892365 TI - Benefits of monitoring plasma levodopa in Parkinson's disease patients with drug induced chorea. AB - We studied the temporal patterns of chorea and plasma levodopa profiles in 30 patients with Parkinson's disease whose motor fluctuations were difficult to characterize and treat on the basis of observation alone. We were able to determine whether chorea was associated with high levodopa concentrations or low levodopa concentrations or both. We found the following patterns of levodopa associated chorea: chorea due to inadequate levodopa levels, chorea due to biphasic levodopa absorption, chorea associated with either rapid or slow levodopa absorption, and chorea due to long-duration levodopa absorption mimicking a sustained-release preparation. Seven patients benefited after their dosing schedules were rearranged as a result of information gained from monitoring. We conclude that any patient with levodopa-associated chorea who cannot be regulated on the basis of observation alone should be studied with simultaneous plasma levodopa measurements and clinical monitoring to detect an unusual plasma levodopa pattern that may be improved by adjustment of dosing schedule. PMID- 1892366 TI - Epilepsy surgery in the posterior cortex. AB - Fourteen (74%) of 19 patients obtained a significant reduction in seizures after posterior corticectomy; 6 (32%) were seizure-free over a median follow-up of 3.7 years (range, 1 to 14 years). Surgery included limited resections of the occipital lobe in 16 patients, posterior temporal region in 11, and posterior portion of parietal lobe in 7. Surgical failure related to probable multiple areas of epileptogenesis (4 patients), or limited resections (2 patients) to preserve visual fields (2 patients) and to avoid dyslexia (1 patient). Of 14 patients without a complete hemianopia preoperatively, 6 (43%) developed a new or increased visual field deficit, 2 (14%) of which were hemianopia. Four (36%) of 11 occipital lobe resections resulted in a new or increased visual field deficit: quadrantanopia in 3 and hemianopia in 1. Visual phenomena were the most common initial ictal symptoms, occurring in 13 (68%) of the 19 patients. Twelve patients had complex partial seizures: in 2, always without warning; in 7, always following an aura, usually visual; and in 3 patients, with or without warning. Scalp electroencephalography identified the origin of most recorded seizures in 12 (63%) of the 19 patients. A principal interictal spike focus appeared in 15 patients (79%), and always correlated with the epileptogenic lobe as defined by scalp and/or subdural-recorded seizures (14 patients) or by clinical analysis and computed tomography (1 patient). PMID- 1892367 TI - Motor responses after transcranial electrical stimulation of cerebral hemispheres with a degenerated pyramidal tract. AB - Motor responses were evoked in the thenar muscles by transcranial electrical cortex stimulation in 5 stroke patients with an isolated lacuna in the internal capsule, in whom wallerian degeneration of the pyramidal tract was demonstrated in vivo. Suprathreshold stimulation of the affected hemisphere elicited bilateral motor responses; whereas, stimulation at identical intensities of the undamaged hemisphere yielded strictly unilateral responses in the contralateral hand, like the responses of all normal control subjects. Focused magnetic brain stimulation was performed in 1 patient and gave identical results. Because muscular excitability to cortical stimulation is preserved in spite of pyramidal tract disruption, other pathways must bypass the lesion. Because of the bilaterality of responses, we suggest polysynaptic corticoreticulospinal connections. PMID- 1892368 TI - High-speed memory scanning in Parkinson's disease: adverse effects of levodopa. AB - High-speed memory scanning as assessed by the Sternberg paradigm was studied in 12 nondemented patients with fluctuating Parkinson's disease and 13 age-matched healthy controls. Patients were first assessed before taking their morning dose of levodopa ("off") and again after that dose had produced full clinical effect ("on") after that dose had produced full clinical effect ("on"). Although motor components of the measured choice reaction time were slower in patients when off than in control subjects, memory scanning speed was not different. After levodopa (on), patients' motor time normalized, but cognitive processing speed became significantly slower when compared with previous performance in the off condition and with controls. Contrary to previous concepts of bradyphrenia in patients with Parkinson's disease, these results indicate that dopaminergic stimulation can reduce cognitive processing speed. PMID- 1892369 TI - Positron emission tomography suggests that the rate of progression of idiopathic parkinsonism is slow. AB - We performed sequential positron emission tomography scans with 6-[18F]fluoro-L dopa in 9 patients with idiopathic parkinsonism and 7 age-matched normal control subjects to compare changes in the nigrostriatal dopaminergic pathway over time. The mean interval between the scans was 3.3 years for the group with idiopathic parkinsonism and 3.9 years for the control subjects. The scans were analyzed by calculating the ratio of striatal to background radioactivity. Both groups showed statistically significant reductions of striatal uptake over the interval. The rate of decrease was almost identical in each group (p = 0.6). We infer that the usual rate of loss of integrity of the dopaminergic nigrostriatal pathway in patients with idiopathic parkinsonism is slow and the rate of change between the two groups was comparable. PMID- 1892370 TI - The time course and magnitude of spontaneous recovery of parkinsonism produced by intracarotid administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine to monkeys. AB - We studied rhesus monkeys with hemiparkinsonism or bilateral parkinsonism produced by unilateral or bilateral intracarotid administration of 1-methyl-4 phenyl-1,2,3,6-tetrahydropyridine. Using a standardized clinical rating scale, 4 hemiparkinsonian monkeys showed a 13 to 56% (mean, 36%) spontaneous improvement during an observation period of up to 25 weeks. Generally, recovery leveled off after 14 weeks. Four bilaterally parkinsonian monkeys showed a 5 to 42% (mean, 22%) improvement over a period of up to 30 weeks. Our findings emphasize that spontaneous recovery is a potentially confounding characteristic of this monkey model when used for assessing novel antiparkinsonian therapies. PMID- 1892371 TI - Deletion of mitochondrial DNA in patients with combined features of Kearns-Sayre and MELAS syndromes. AB - A 9-year-old girl and an 11-year-old boy had ptosis, progressive external ophthalmoplegia, pigmentary retinopathy, and sensorineural hearing loss. The girl had diabetes mellitus and the boy had hypoparathyroidism. Both children also developed recurrent vomiting and cerebral infarcts with lactic acidosis. Muscle biopsy specimens showed ragged-red fibers and Southern analysis demonstrated a distinct heteroplasmic deletion of muscle mitochondrial DNA in each patient but no evidence of the point mutation in the transfer RNALeu(UUR) gene recently identified in mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS). These 2 children had combined features of Kearns-Sayre syndrome and MELAS, suggesting that mitochondrial DNA deletions occasionally can have pleomorphic clinical expression. PMID- 1892372 TI - Fatal disseminated hemorrhagic toxoplasmic encephalitis as the initial manifestation of AIDS. AB - A 28-year-old woman presented with progressive coma after being asymptomatic for 1 year after the demonstration of seropositivity for human immunodeficiency virus and high serum immunoglobulin G toxoplasma titers. Computed tomographic scanning showed multiple rounded cerebral hemorrhages and massive cerebral edema. Postmortem examination disclosed Toxoplasma gondii cysts scattered throughout the brain. An overwhelming fatal toxoplasmosis associated with multiple cerebral hemorrhages may be the first presentation of the acquired immunodeficiency syndrome. We raise the possibility that frequent neuroradiological monitoring may be indicated in asymptomatic human immunodeficiency virus-infected patients with high immunoglobulin G toxoplasma titers. PMID- 1892373 TI - Paraneoplastic cerebellar autoantibodies associated with gynecological cancer bind to myenteric plexus neurons. PMID- 1892374 TI - Guillain-Barre syndrome and plasmapheresis in childhood. PMID- 1892376 TI - The diagnosis of multiple system atrophy. PMID- 1892377 TI - Development and application of a multiple typing system for Clostridium difficile. AB - A combination of bacteriocin, bacteriophage, and plasmid typing techniques was used to differentiate strains of Clostridium difficile. A typing set of 20 bacteriocin-producing strains was established after 400 isolates of C. difficile were screened for the ability to produce bacteriocin. These strains were used to type a collection of 114 isolates of C. difficile. Forty-six (40%) of the 114 isolates were typeable, and 31 typing patterns were distinguishable. Plasmid typing of the same 114 isolates of C. difficile showed that 67 (59%) of the isolates carried up to four plasmids ranging from 7 to 60 kb in size, although most strains contained only one or two plasmids. Twenty different plasmid typing patterns were observed among the isolates. A combination of bacteriocin and plasmid typing provided 77% typeability. Fifteen (13%) of the 114 strains were typeable with five bacteriophages isolated in our laboratory, but the increase in typeability of strains over that obtainable by plasmid and bacteriocin typing was only 1.8%. Isolates that were nontypeable by bacteriocins, plasmids, or phages could be divided into two groups on the basis of positive or negative cytotoxin production. This further division of strains would increase the typeability potential by 7%; i.e., the ability to differentiate strains would rise from 77 to 84%, or perhaps 86%, if phage typing were included. We conclude that more than one of the techniques reported in this paper must be used to achieve an acceptable level of typeability of this species. PMID- 1892378 TI - Chemical control of interstrain competition for soybean nodulation by Bradyrhizobium japonicum. AB - Previous research has shown that a significant limitation to the agricultural use of improved rhizobial inoculant strains is competition from the indigenous soil population. In this work, we sought to test whether chemical inhibitors of flavonoid-induced nod gene expression in Bradyrhizobium japonicum could be identified and utilized to affect interstrain competition for nodulation of soybeans. Approximately 1,000 structural and functional analogs of the known, natural inducers of nod gene expression were tested on six strains of B. japonicum containing a nodY-lacZ fusion. We successfully identified effective inhibitors of nodY expression. The addition of the inhibitor 7-hydroxy-5 methylflavone significantly inhibited nodulation by a sensitive strain and could be used to effectively manipulate the competition between strains for soybean nodulation. However, this work also uncovered significant limitations for the practical use of this methodology. For example, despite the almost universal induction response to the identified natural inducers, there was a wide variability among strains in their response to any specific inhibitor. Given this unexpected variability, the cost of registration of an agronomic chemical, and the potential for the development of resistant field populations, it is unlikely that chemical inhibitors can be successfully applied to a field situation. PMID- 1892379 TI - Nature of Escherichia coli cell lysis by culture supernatants of Bacillus species. AB - Escherichia coli cells were found to be sensitive to lysis by the supernatants of a variety of protease-positive Bacillus species when treated at 45 degrees C but not when treated at 37 degrees C. Different E. coli strains manifested different lysis sensitivities when treated at 45 degrees C. When the lysis rates of E. coli cells at various stages of growth were investigated, post-exponential-phase cells were shown to be most sensitive to lysis. The lysis rate was inversely related to cell viability, and susceptibility appeared to be at least partly due to lysis of dead E. coli cells. A close relation was observed between levels of lysis activity and proteolytic activity. A Bacillus subtilis mutant lacking alkaline and neutral protease activity failed to lyse E. coli cells. It was concluded that Bacillus proteases played a major role in the observed E. coli lysis. PMID- 1892380 TI - Use of a xylE marker gene to monitor survival of recombinant Pseudomonas putida populations in lake water by culture on nonselective media. AB - IncQ marker plasmids were previously constructed to enable the analysis of the survival of populations of Pseudomonas putida released into lake water (C. Winstanley, J. A. W. Morgan, R. W. Pickup, J. G. Jones, and J. R. Saunders, Appl. Environ. Microbiol. 55:771-777, 1989). We constructed equivalent IncP plasmids, pLV1016 and pLV1017, to provide conjugative alternative systems. Detection of the xylE gene carried by marker plasmids was found to be a valid indicator to use for studying the survival of released populations by culturing on nonselective media. These plasmids were used to study the survival of populations of Pseudomonas putida in both sterile and untreated lake water. The effects of inoculum size, the metabolic burden imposed on the cell by the unregulated expression of xylE, and an auxotrophic mutation carried by the host strain were studied. We also assessed the reproducibility and hence the predictability of the survival of released populations. Model systems with a single lake water sample and model systems with three different lake water samples, taken from the same site in consecutive months, were used to analyze variability between replicates and to assess differences caused by host strain or water sample. A large variability was found depending on which water sample was used. These findings imply that it will be difficult to predict accurately the survival of released populations in the natural environment. PMID- 1892381 TI - Successful approach for detection of low numbers of enterotoxigenic Escherichia coli in minced meat by using the polymerase chain reaction. AB - The polymerase chain reaction (PCR) was used as a tool for the detection of enterotoxigenic Escherichia coli in minced meat. With two synthetic 29-mer oligonucleotides, a 195-bp fragment from the E. coli heat-labile enterotoxin (LT) gene could be amplified specifically. When 6 CFU was added to the reaction mixture as a template, the PCR yielded sufficient amplified product for visualization on an agarose gel. Prior to PCR amplification, the minced meat samples were subjected to enrichment culturing for E. coli. From these cultures, 10 microliters was used in the PCR assay. All 20 25-g samples that were examined in this assay were negative for E. coli LT. However, when 3 CFU of E. coli LT was added to the 25-g samples of minced meat prior to enrichment culturing, the PCR assay yielded positive results. PMID- 1892382 TI - Degradation of 2,4,6-trichlorophenol by Azotobacter sp. strain GP1. AB - A bacterium which utilizes 2,4,6-trichlorophenol (TCP) as a sole source of carbon and energy was isolated from soil. The bacterium, designated strain GP1, was identified as an Azotobacter sp. TCP was the only chlorinated phenol which supported the growth of the bacterium. Resting cells transformed monochlorophenols, 2,6-dichlorophenol, and 2,3,6-trichlorophenol. Phenol and a number of phenolic compounds, including 4-methylphenol, all of the monohydroxybenzoates, and several dihydroxybenzoates, were very good carbon sources for Azotobacter sp. strain GP1. The organism utilized up to 800 mg of TCP per liter; the lag phase and time for degradation, however, were severely prolonged at TCP concentrations above 500 mg/liter. Repeated additions of 200 mg of TCP per liter led to accelerated degradation, with an optimum value of 100 mg of TCP per liter per h. TCP degradation was significantly faster in shaken than in nonshaken cultures. The optimum temperature for degradation was 25 to 30 degrees C. Induction studies, including treatment of the cells with chloramphenicol prior to TCP or phenol addition, revealed that TCP induced TCP degradation but not phenol degradation and that phenol induced only its own utilization. Per mol of TCP, 3 mol of Cl- was released. 2,6-Dichloro-p benzoquinone was detected in the resting-cell medium of Azotobacter sp. strain GP1. By chemical mutagenesis, mutants blocked in either TCP degradation or phenol degradation were obtained. No mutant defective in the degradation of both phenols was found, indicating separate pathways for the dissimilation of the compounds. In some of the phenol-deficient mutants, pyrocatechol was found to accumulate, and in some of the TCP-deficient mutants, 2,6-dichlorohydroquinone was found to accumulate. PMID- 1892383 TI - Relationship between hydrogen consumption, dehalogenation, and the reduction of sulfur oxyanions by Desulfomonile tiedjei. AB - Resting-cell suspensions of Desulfomonile tiedjei consumed H2 with 3-chloro-, 3 bromo-, and 3-iodobenzoate as electron acceptors with rates of 0.50, 0.44, and 0.04 mumol h-1 mg-1, respectively. However, benzoate and 3-fluorobenzoate were not metabolized by this bacterium. In addition, H2 uptake was at least fourfold faster when sulfate, sulfite, or thiosulfate was available as the electron acceptor instead of a haloaromatic substrate. When sulfite and 3-chlorobenzoate were both available for this purpose, the rate of H2 uptake by D. tiedjei was intermediate between that obtained with either electron acceptor alone. Hydrogen concentrations were reduced to comparably low levels when either 3 chlorobenzoate, sulfate, or sulfite was available as an electron acceptor, but significantly less H2 depletion was evident with benzoate or nitrate. Rates of 3 chlorobenzoate dechlorination increased from an endogenous rate of 14.5 to 17.1, 74.0, 81.1, and 82.3 nmol h-1 mg-1 with acetate, pyruvate, H2, and formate, respectively, as the electron donors. Sulfite and thiosulfate inhibited dehalogenation, but sulfate and NaCl had no effect. Dehalogenation and H2 metabolism were also inhibited by acetylene, molybdate, selenate, and metronidazole. Sulfite reduction and dehalogenation were inhibited by the same respiratory inhibitors. These results suggest that the reduction of sulfite and dehalogenation may share part of the same electron transport chain. The kinetics of H2 consumption and the direct inhibition of dehalogenation by sulfite and thiosulfate in D. tiedjei cells clearly indicate that the reduction of sulfur oxyanions is favored over aryl dehalogenation for the removal of reducing equivalents under anaerobic conditions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1892384 TI - Mutants of Pseudomonas cepacia G4 defective in catabolism of aromatic compounds and trichloroethylene. AB - Pseudomonas cepacia G4 possesses a novel pathway of toluene catabolism that is shown to be responsible for the degradation of trichloroethylene (TCE). This pathway involves conversion of toluene via o-cresol to 3-methylcatechol. In order to determine the enzyme of toluene degradation that is responsible for TCE degradation, chemically induced mutants, blocked in the toluene ortho monooxygenase (TOM) pathway of G4, were examined. Mutants of the phenotypic class designated TOM A- were all defective in their ability to oxidize toluene, o cresol, m-cresol, and phenol, suggesting that a single enzyme is responsible for conversion of these compounds to their hydroxylated products (3-methylcatechol from toluene, o-cresol, and m-cresol and catechol from phenol) in the wild type. Mutants of this class did not degrade TCE. Two other mutant classes which were blocked in toluene catabolism, TOM B-, which lacked catechol-2,3-dioxygenase, and TOM C-, which lacked 2-hydroxy-6-oxoheptadienoic acid hydrolase activity, were fully capable of TCE degradation. Therefore, TCE degradation is directly associated with the monooxygenation capability responsible for toluene, cresol, and phenol hydroxylation. PMID- 1892385 TI - Bacteriological composition and structure of granular sludge adapted to different substrates. AB - The bacteriological composition and ultrastructure of mesophilic granular methanogenic sludge from a large-scale Upflow Anaerobic Sludge Blanket reactor treating wastewater from a sugar plant and of sludge granules adapted to ethanol and propionate were studied by counting different bacterial groups and by immunocytochemical methods. Propionate-grown granular sludge consisted of two types of clusters, those of a rod-shaped bacterium immunologically related to Methanothrix soehngenii and those consisting of two different types of bacteria with a specific spatial orientation. One of these bacteria reacted with antiserum against Methanobrevibacter arboriphilus AZ, whereas the other is most likely a propionate-oxidizing bacterium immunologically unrelated to Syntrophobacter wolinii. Sludge granules obtained from the large-scale Upflow Anaerobic Sludge Blanket reactor and granules cultivated on ethanol did not show the typical spatial orientation of bacteria. Examination of the bacterial composition of the three types of granules by light and electron microscopy, the most-probable number method, and by isolations showed that M. arboriphilus and M. soehngenii were the most abundant hydrogenotrophic and acetoclastic methanogens in propionate-grown sludge. Methanospirillum hungatei and Methanosarcina barkeri predominated in ethanol-grown granules, whereas many morphotypes of methanogens were abundant in granules from the full-scale reactor. PMID- 1892386 TI - Multiplication of Legionella spp. in tap water containing Hartmannella vermiformis. AB - A model was developed to study the multiplication of various Legionella spp. in tap water containing Hartmannella vermiformis. Tap water cultures prepared with the following components were suitable for the multiplication studies: Legionella spp., 10(3) CFU/ml; H. vermiformis, 10(4.4) cysts per ml; and killed Pseudomonas paucimobilis, 10(9) cells per ml. Cocultures were incubated at 37 degrees C for at least 1 week. The following legionellae multiplied in tap water cocultures in each replicate experiment: L. bozemanii (WIGA strain), L. dumoffii (NY-23 and TX KL strains), L. micdadei (two environmental strains), and L. pneumophila (six environmental strains and one clinical isolate). Growth yield values for these strains were 0.6 to 3.5 log CFU/ml. Legionellae which did not multiply in replicate cocultures included L. anisa (one strain), L. bozemanii (MI-15 strain), L. micdadei (a clinical isolate), L. longbeachae, (one strain), and L. pneumophila (Philadelphia 1 strain). L. gormanii and an environmental isolate of L. pneumophila multiplied in only one of three experiments. None of the legionellae multiplied in tap water containing only killed P. paucimobilis. The mean growth yield (+/- standard deviation) of H. vermiformis in the cocultures was 1.2 +/- 0.1 log units/ml. H. vermiformis supports multiplication of only particular strains of legionellae, some of which are from diverse origins. PMID- 1892387 TI - Bacterial species dominance within a binary culture biofilm. AB - Studies with two species of bacteria, Pseudomonas putida and Hyphomicrobium sp. strain ZV620, were carried out to evaluate the overall net rate of accumulation of biofilm, the biofilm species composition, and individual species shear-related removal rates. Bacterial cells of either or both species were deposited onto glass or biofilm surfaces to initiate multispecies biofilms. Subsequent biofilm development was carried out under known conditions of nutrient concentration and laminar flow. Establishment of a depositing organism in a biofilm composed of another species was found to be a function of the relative growth rates of the bacterial species. In the case of simultaneous species deposition and subsequent binary culture development, the faster-growing organisms rapidly became the dominant biofilm species, but the slower-growing organisms remained established within the biofilm and continued to increase in numbers over time. The results also indicated that the rate of cell removal by fluid shear for a species was a function of biofilm cell number only if the species concentration was uniform with depth; in essence, only the upper layers of the biofilm were sheared off. PMID- 1892388 TI - Experimental apparatus for selection of adherent microorganisms under stringent growth conditions. AB - A bioreactor apparatus is described for studying bacterial attachment. A cyclic, on-off, flow regime was imposed within the apparatus. Model calculations illustrate the utility of this flow pattern in the selection and maintenance of slow-growing, adherent organisms. The apparatus is believed to have general utility in testing bacterial attachment influenced by many types of experimental or environmental constraints, including variations in fluid dynamics, presence of toxic substances (metals or organics), nature of the substratum surface, concentrations of limiting nutrients, and competition between bacterial strains. As an example application, the apparatus was employed to test 14 bacterial strains for surface attachment in a nutrient-limited growth medium. The medium was developed, using the chemical equilibrium program MINEQL, for planned studies of biofilms in a solution with a chemically defined composition that permits calculation of trace metal speciation. The apparatus was used to select organisms with growth and attachment characteristics that could not be evaluated by conventional batch, or chemostat, culture conditions. When supplied with acetate, pyruvate, or succinate as a carbon and energy source, the gram-negative strains Pseudomonas cepacia 17616 and Zoogloea sp. WGO4 showed superior attachment characteristics to glass surfaces in the chemically defined medium but only moderate fluid-phase growth. The gram-positive Arthrobacter sp. strain 9G4D and gram-negative species P. pickettii and Zoogloea sp. WNJ8, when supplied with pyruvate as a carbon and energy source, were capable of superior growth in the fluid phase but formed only a low to moderate biofilm surface coverage. PMID- 1892389 TI - In situ measurement of methane oxidation in groundwater by using natural-gradient tracer tests. AB - Methane oxidation was measured in an unconfined sand and gravel aquifer (Cape Cod, Mass.) by using in situ natural-gradient tracer tests at both a pristine, oxygenated site and an anoxic, sewage-contaminated site. The tracer sites were equipped with multilevel sampling devices to create target grids of sampling points; the injectate was prepared with groundwater from the tracer site to maintain the same geochemical conditions. Methane oxidation was calculated from breakthrough curves of methane relative to halide and inert gas (hexafluroethane) tracers and was confirmed by the appearance of 13C-enriched carbon dioxide in experiments in which 13C-enriched methane was used as the tracer. A Vmax for methane oxidation could be calculated when the methane concentration was sufficiently high to result in zero-order kinetics throughout the entire transport interval. Methane breakthrough curves could be simulated by modifying a one-dimensional adevection-dispersion transport model to include a Michaelis Menten-based consumption term for methane oxidation. The Km values for methane oxidation that gave the best match for the breakthrough curve peaks were 6.0 and 9.0 microM for the uncontaminated and contaminated sites, respectively. Natural gradient tracer tests are a promising approach for assessing microbial processes and for testing in situ bioremediation potential in groundwater systems. PMID- 1892390 TI - Some chemical and physical properties of extracellular polysaccharides produced by Butyrivibrio fibrisolvens strains. AB - Most strains of Butyrivibrio fibrisolvens are known to produce extracellular polysaccharides (EPs). However, the rheological and functional properties of these EPs have not been determined. Initially, 26 strains of Butyrivibrio were screened for EP yield and apparent viscosities of cell-free supernatants. Yields ranged from less than 1.0 to 16.3 mg per 100 mg of glucose added to the culture. Viscosities ranged from 0.71 to 5.44 mPa.s. Five strains (CF2d, CF3, CF3a, CE51, and H10b) were chosen for further screening. The apparent viscosity of the EP from each of these strains decreased by only 50 to 60% when the shear rate was increased from 20 to 1,000 s-1. Strain CE51 produced the EP having the highest solution viscosity. A detailed comparison of shear dependency of the EP from strain CF3 with xanthan gum showed that this EP was less shear sensitive than xanthan gum and, at a shear rate of 1,000 s-1, more viscous. EPs from strains CF3 and H10b were soluble over a wide range of pH (1 to 13) in 80% (vol/vol) ethanol water or in 1% (wt/vol) salt solutions. The pH of 1% EP solutions was between 4.5 and 5.5. Addition of acid increased solution viscosities, whereas addition of base decreased viscosity. EPs from strains CF3, CE51, and H10b displayed qualitatively similar infrared spectra. Calcium and sodium were the most abundant minerals in the three EPs. The amounts of magnesium, calcium, and iron varied considerably among the EPs, but the potassium contents remained relatively constant. PMID- 1892391 TI - D-value determinations are an inappropriate measure of disinfecting activity of common contact lens disinfecting solutions. AB - Determination of a D value for specific test organisms is a component of the efficacy evaluation of new contact lens disinfecting solutions. This parameter is commonly defined as the time required for the number of surviving microorganisms to decrease 1 logarithmic unit. The assumption made in establishing a D value is that the rate of kill exhibits first-order kinetics under the specified conditions. Such exponential kill rates are seen with thermal contact lens disinfection system. A comparison of the death rate kinetics for a variety of chemical contact lens disinfecting solutions was undertaken to ascertain the suitability of D-value determination for these chemical disinfectants. The active agents of these different solutions included hydrogen peroxide, thimerosal, chlorhexidine, tris(2-hydroxyethyl)tallow ammonium chloride, thimerosal, polyaminopropyl biguanide, and polyquaternium-1. The solutions were challenged with 10(6) CFU of either Pseudomonas aeruginosa, Serratia marcescens, or Staphylococcus hominis per ml, and survival rate was determined. This study clearly demonstrates the nonlinear nature of the inactivation curves for most contact lens chemical disinfecting solutions for the challenge organisms. D-value determination is, therefore, an inappropriate method of reporting the biocidal activity of these solutions. PMID- 1892392 TI - Use of an A-T-rich DNA clone for identification and detection of Peronosclerospora sorghi. AB - A recombinant plasmid, pMLY12-1, screened from a Peronosclerospora sorghi library hybridizes only to DNA of P. sorghi, or to DNA from leaves infected with P. sorghi, not to DNA of P. sorghi Thailand isolate, P. philippinensis, P. sacchari, or P. maydis. The terminal sequences of the 1.3-kb insert, which appears to contain mitochondrial DNA, are 85% A and T. No polymorphisms were detected when the probe was hybridized to Southern blots containing DNA from P. sorghi pathotype 1, pathotype 3, or a Botswana isolate digested with any of the eight restriction endonucleases tested. The banding patterns were the same whether DNA was extracted directly from the fungus or from infected leaves. PMID- 1892394 TI - Survival of Agrobacterium radiobacter K84 on various carriers for crown gall control. AB - Screening was performed on nine carriers to find an improved formulation for Agrobacterium radiobacter K84 cells. The survival data showed that it is possible to preserve A. radiobacter cells on dry solid supports for a long time provided that the storage temperature is 4 degrees C and that the inoculation volume for 4 x 10(9) CFU g-1 is not less than 0.15 ml g of carrier-1. On the other hand, a substantial carrier water content was necessary for room temperature storage. Many materials proved to be suitable as microbial carriers; in some cases, vermiculite allowed long storage times comparable to those reported for peat or carboxymethyl cellulose, which are already employed in some commercial A. radiobacter K84 products. Furthermore, vermiculite assured full and immediate biological activity in the prevention of crown gall, showing that it is suitable for a new formulation of strain K84. A hypothesis to explain the different survival abilities in wet and dry conditions is presented. PMID- 1892393 TI - Reductive dechlorination of Tri- and tetrachloroethylenes depends on transition from aerobic to anaerobic conditions. AB - Aerobic enrichment cultures from contaminated groundwaters dechlorinated trichloroethylene (TCE) (14.6 mg/liter; 111 mumol/liter) and tetrachloroethylene (PCE) (16.2 mg/liter; 98 mumol/liter) reductively within 4 days after the transition from aerobic to anaerobic conditions. The transformation products were equimolar amounts of cis-1,2-dichloroethylene and traces of 1,1-dichloroethylene. No other chlorinated product and no methane were detected. The change was accompanied by the release of sulfide, which caused a decrease in the redox potential from 0 to -150 mV. In sterile control experiments, sulfide led to the abiotic formation of traces of 1,1-dichloroethylene without cis-1,2 dichloroethylene production. The reductive dechlorination of PCE via TCE depended on these specific transition conditions after consumption of the electron acceptor oxygen or nitrate. Repeated feeding of TCE or PCE to cultures after the change to anaerobic conditions yielded no further dechlorination. Only aerobic subcultures with an air/liquid ratio of 1:4 maintained dechlorination activities; anaerobic subcultures showed no transformation. Bacteria from noncontaminated sites showed no reduction under the same conditions. PMID- 1892395 TI - The secretion leader of Mucor pusillus rennin which possesses an artificial Lys Arg sequence directs the secretion of mature human growth hormone by Saccharomyces cerevisiae. AB - The prepro-peptide of fungal aspartic proteinase, Mucor pusillus rennin, is useful as a secretion leader for efficient secretion of human growth hormone (HGH) from Saccharomyces cerevisiae. For secretion by yeast cells of HGH with the same NH2 terminus as native HGH, an artificial Lys-Arg linker, which is one of the potential KEX2 recognition sequences, was introduced at the junction between the M. pusillus rennin secretion leader and mature HGH. The HGH directed by this construction was the same size as native HGH, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and amino acid sequencing of its NH2 terminus revealed that the secretion leader peptide was removed correctly at the COOH-terminal side of the Lys-Arg linker. On the other hand, when the same plasmid was expressed in a kex2 mutant strain, unprocessed HGH of a higher molecular weight was secreted, indicating that no proteolytic cleavage at the Lys Arg site occurred. These results clearly showed that the leader peptide with the Lys-Arg linker was recognized and specifically cleaved by the yeast KEX2 protease. The mature HGH purified from yeast culture medium was indistinguishable from native HGH in biological activity, determined by the adipocyte conversion assay, and in secondary structure, determined by circular dichroism spectroscopy. PMID- 1892396 TI - Quantitative assessment of the germicidal efficacy of ultrasonic energy. AB - Propagated (free-field) ultrasonic energy at a frequency of 26 kHz was used to expose aqueous suspensions of bacteria (Escherichia coli, Staphylococcus aureus, Bacillus subtilis, and Pseudomonas aeruginosa), fungus (Trichophyton mentagrophytes), and viruses (feline herpesvirus type 1 and feline calicivirus) to evaluate the germicidal efficacy of ultrasound. There was a significant effect of time for all four bacteria, with percent killed increasing with increased duration of exposure, and a significant effect of intensity for all bacteria except E. coli, with percent killed increasing with increased intensity level. There was a significant reduction in fungal growth compared with that in the controls, with decreased growth with increased ultrasound intensity. There was a significant reduction for feline herpesvirus with intensity, but there was no apparent effect of ultrasound on feline calicivirus. These results suggest that ultrasound in the low-kilohertz frequency range is capable to some degree of inactivating certain disease agents that may reside in water. The physical mechanism of inactivation appears to be transient cavitation. PMID- 1892397 TI - Potential for thermophilic (50 degrees C) anaerobic dechlorination of pentachlorophenol in different ecosystems. AB - Thermophilic (50 degrees C) anaerobic biodegradation of pentachlorophenol (PCP) was investigated by using different inocula from natural ecosystems and anaerobic digesters. The inocula tested were three freshwater sediments, four anaerobic sewage sludge samples from digesters treating sludge from wastewater plants with various industrial inputs, and digested manure from an anaerobic reactor. Only one digested-sludge sample and the manure sample were from thermophilic environments. The initial PCP concentration was 7.5 or 37.5 microM. After 8 months, PCP had disappeared from the sediment samples and various, less chlorinated intermediates were present. Additions of extra PCP were degraded within 4 weeks, and a maximal observed dechlorination rate of 1.61 mumol/liter/day in the vials with addition of 7.5 microM PCP and 7.50 mumol/liter/day in the vials with addition of 37.5 microM PCP were measured for a freshwater sediment. In contrast, only 2.8 to 17.5% of the initial PCP added had disappeared from the sludge samples after 8 months of incubation. The complex pattern of intermediates formed indicated that the dechlorination of PCP proceeded via different pathways, involving at least two different populations in the dechlorination processes. PMID- 1892398 TI - Examination of retail chickens and sausages in Britain for vero cytotoxin producing Escherichia coli. AB - Samples from chickens and pork sausages were examined for the presence of Vero cytotoxin-producing Escherichia coli by using DNA probes for the Vero cytotoxin genes. Hybridization was detected in 25% of the 184 sausage samples, but none of the chickens was positive. No E. coli O157:H7 strains were isolated, and serotyping showed that the Vero cytotoxin-producing E. coli strains belonged to eight different O serogroups and that six strains had an unidentifiable O antigen. PMID- 1892399 TI - Rapid and sensitive assay for the phytotoxin rhizobitoxine. AB - Rhizobitoxine is a phytotoxin synthesized by some strains of the legume symbiont genus Bradyrhizobium and the plant pathogen Pseudomonas andropogonis. We demonstrate here a new enzymatic assay which is 100-fold more sensitive than previous assays and can detect as little as 1.0 pmol of rhizobitoxine. The assay is based on the inhibition of Salmonella typhimurium beta-cystathionase by rhizobitoxine. Interestingly, beta-cystathionase from Bradyrhizobium japonicum is insensitive to rhizobitoxine at concentrations lower than 75 microM. PMID- 1892400 TI - Cytotoxicity of T-2 toxin and its metabolites determined with the neutral red cell viability assay. AB - The neutral red (NR) cell viability assay was used with various cell types of human origin to quantitate the potency of T-2 mycotoxin and its metabolites. The human melanoma SK-Mel/27 cell line was the most sensitive, with a midpoint cytotoxicity value of 2.8 ng of T-2 per ml. With the human hepatoma cell line, HepG2, the sequence of potency for a series of mycotoxins was T-2 greater than HT 2 greater than T-2 triol greater than T-2 tetraol. PMID- 1892401 TI - Diagnosis and surgical treatment of congenital cartilaginous rests of the neck. PMID- 1892402 TI - Generalized pustular psoriasis. A review of 63 cases. AB - BACKGROUND: Sixty-three patients with generalized pustular psoriasis were hospitalized during a 29-year period. They were classified into four subgroups on the basis of onset and morphologic pattern of disease: acute (von Zumbusch), subacute annular, chronic (acral), and mixed. This division provides a better understanding of the variability of the disease and helps in choosing treatment. OBSERVATIONS: The average age at onset was 50 years; male and female patients were affected about equally. In 11 patients, flares were precipitated by localized infections. Approximately one fourth of the patients had complications; most were superinfections. The average stay in the hospital was 30 days; factors correlating with a long hospitalization were hypocalcemia, female sex, and a previous history of psoriasis vulgaris or pustular psoriasis. CONCLUSIONS: Whereas topical therapy was helpful, systemic medications were often needed. Coal tar, ultraviolet light, and psoralen-ultraviolet A may be effective; however, they must be used with caution, because they may exacerbate the disease. PMID- 1892403 TI - Dysplastic nevi. Occurrence in first- and second-degree relatives of patients with 'sporadic' dysplastic nevus syndrome. AB - In this study a cross-sectional survey was undertaken among 156 living family members of 31 probands originally classified as having sporadic (histologically verified) dysplastic nevus syndrome (DNS). Seven (13.2%) of 53 parents had clinically recognizable DNS. Twenty-six (36.1%) of the 72 sibs showed dysplastic nevi. The diagnosis of DNS in family members was based on mainly clinical examination; in eight family members--those with only mild manifestation of DNS- a nevus was removed for histologic confirmation. After correction for pedigree size, we found that 60% of patients with "type A sporadic" DNS actually had one or more relatives with a DNS phenotype. Only 25% (8/30) of the probands were ultimately true sporadic cases without a DNS-affected first- or second-degree relative. In 15% (5/31) of the probands no conclusions concerning the type of DNS could be made because the pedigree size did not allow such a conclusion. We also found a higher prevalence of dysplastic nevi among the younger generation as compared with the older generation in our probands with DNS and their families as well as in a general population study of 400 individuals. This generation dependent difference in expression of the DNS phenotype suggests that besides a genetic factor, other factors may play a role in the development of the characteristic phenotype. PMID- 1892405 TI - Linear focal elastosis. An ultrastructural study. AB - We studied an 86-year-old Japanese man with linear focal elastosis. The lesions were asymptomatic yellow striae in the lumbar region, histologically composed of massive, well-demarcated basophilic fibers that stained positively with elastic tissue stains. Electron microscopy revealed fine, reticular or granular electron dense materials, and elastic fiber microfibril-like materials in the matrix, in addition to numerous mature and immature elastic fibers. These findings suggest that active elastogenesis was occurring in the lesions. The four cases reported so far have the three common features of age, sex, and lesion location. PMID- 1892404 TI - Antibiotic prophylaxis of wound infections in skin surgery. AB - A controlled prospective study of 2165 outpatients undergoing skin surgery was performed to evaluate the utility and the effects of several antibiotic schedules for prophylaxis of wound infections. The patients were divided into four groups. Twenty-three of the 541 group A patients, given no antibiotics, had wound infections. Eight of the 542 group B patients, given systemic antibiotics from immediately after surgery until the third day, had wound infections. Four of the 540 group C patients, treated only with local sterile antibiotic powder sprinkled into the wound during surgery, had wound infections develop, and only one infection occurred in the 542 group D patients given systemic antibiotics from 2 days before surgery until the second day after surgery. This last schedule was the best for prophylaxis of wound infections in contamination-prone regions. Local antibiotic administration is a simple method for prevention of infections in routine skin surgery. PMID- 1892406 TI - Transient intraepidermal bullous reaction after skin graft for toxic epidermal necrolysis. Ultrastructural and immunohistochemical features similar to those of inherited epidermolysis bullosa simplex. AB - Blister formation in skin graft donor or recipient sites is uncommon. We describe a 49-year-old female patient with bullae in sites of grafts used in the treatment of toxic epidermal necrolysis. Generalized loss of skin developed 3 weeks after she had ingested phenobarbital. Sixty days after the beginning of the toxic epidermal necrolysis, the reepidermization was only 80% and skin grafts were placed on lower-extremity and abdominal wounds using the first healed sites as donor sites. Several bullae and erosions were noted on grafted areas 3 weeks later. Skin biopsy specimens revealed separation at the dermoepidermal junction, and no autoantibodies were detected by direct and indirect immunofluorescence. Electron microscopy demonstrated that the blister was formed through the basal keratinocytes and that the dermoepidermal junction, including hemidesmosomes and anchoring fibrils, was normal. Immunofluorescence mapping was performed using polyclonal antibodies from the serum of patients with bullous pemphigold and epidermolysis bullosa acquisita and monoclonal antibodies against GB3 antigen and collagen type VII. All but the bullous pemphigold serum gave positive results; only faint and focal staining of the dermoepidermal junction was observed with bullous pemphigold serum. These findings are the same as those encountered in hereditary epidermolysis bullosa simplex. A biopsy performed 1 year later in the same site as the first one revealed that bullous pemphigold antigen was normally expressed. Keratinocytes autografted in the treatment of toxic epidermal necrolysis may become transiently, functionally abnormal because of the alteration of recipient sites. PMID- 1892407 TI - The invisible dermatoses. AB - The central tenet of invisible dermatology is that visible lesions represent a late stage of development. The eye is an unreliable instrument for judging the normalcy of skin. In chronic widespread dermatoses, the uninvolved skin is at least physiologically abnormal. Recently healed skin is always abnormal. Recognition of occult changes will have a substantial impact on the prevention and treatment of diseases of the skin. PMID- 1892408 TI - Cutaneous manifestations of human immunodeficiency virus infection. Part I. AB - The prevalence of dermatologic problems during the course of human immunodeficiency virus infection makes knowledge of these skin manifestations imperative to all practicing dermatologists. Detection of early infection is encouraged as effective therapy now exists both to delay the progression of human immunodeficiency virus-induced immunodeficiency and to prevent opportunistic infections. Skin manifestations of human immunodeficiency virus infection discussed in this article include the following groups: neoplastic, ie, Kaposi's sarcoma, lymphoma, and squamous cell carcinoma; infectious, ie, viral, bacterial, fungal, protozoal, and arthropod infestations; and a miscellaneous group including papulosquamous, papular, vascular, autoimmune, oral, and drug-related skin disorders. PMID- 1892409 TI - Albert Kligman--master of dermatology. PMID- 1892410 TI - Antibiotic prophylaxis of wound infections in skin surgery. Is 4 days too much? PMID- 1892411 TI - Recurrent dermatitis overlying a prosthetic hip. Eosinophilic cellulitis (Wells' syndrome). PMID- 1892412 TI - Annular plaques on the dorsa of the hands. Neutrophilic eccrine hidradenitis. PMID- 1892413 TI - Extensive purpuric and yellowish papules and plaques with an annular configuration. Erythema elevatum diutinum (EED). PMID- 1892414 TI - A giant in the field: Albert Montgomery Kligman. PMID- 1892415 TI - Another view concerning the proposal to change the name of the American Academy of Dermatology. PMID- 1892416 TI - Ichthyosis, exocrine pancreatic insufficiency, impaired neutrophil chemotaxis, growth retardation, and metaphyseal dysplasia. PMID- 1892417 TI - Generalized pustular psoriasis and idiopathic hypoparathyroidism. PMID- 1892418 TI - Weed wacker dermatitis. PMID- 1892419 TI - Low-dose cyclosporine A in the treatment of disabling morphea. PMID- 1892420 TI - The use of peritoneum for vaginoplasty in 24 patients with congenital absence of the vagina. AB - Vaginoplasty using pelvic peritoneum (Rothman's method) was used in 24 patients with congenital absence of the vagina. The results are presented. Rothman (1972) described vaginoplasty using pelvic peritoneum. We have operated on 24 patients with the anomaly. In this report, the better technique for this operation and the results of treatment are evaluated using data from these 24 cases. PMID- 1892421 TI - Scalp heat flux in postmature and in growth-retarded fetuses. AB - Postterm and growth-retarded fetuses share a common problem which can be characterized by a discrepancy between the supply of oxygen and nutrients to, and the demand of the fetus. But, this "insufficient" placental exchange function may also extend to and affect its thermal homeostasis; e.g. when the capacity of convective (placenta) pathways is shifted towards conductive (surface) pathways for heat loss. Therefore, fetal scalp heat flux measurements, where heat serves as an intrinsic tracer for metabolic activity and placental exchange function, promised a new kind of information. In 81 pregnant women during labor we measured fetal scalp heat flux by means of an heat flux transducer attached to the fetal head and after the cervix had dilated to 3 cm. In the healthy fetuses we found a positive linear relationship between scalp heat flux and different anthropometric variables such as body length (r = 0.432, n = 65, P less than 0.01), head circumference and gestational age. In comparison, postmature and growth-retarded fetuses showed higher heat flux values than appropriately grown fetuses of the same length head size and gestational age. Moreover, in those fetuses scalp heat flux decreased by approximately 4 watt/m2 during the second stage and differed in this regard from the control group who showed stable values during labor and delivery. We conclude that scalp heat flux measurements may indicate disturbances of placental exchange before acute hypoxia occurs. PMID- 1892422 TI - The rise of serum creatinine levels during labor. AB - Serum creatinine, blood urea nitrogen and creatine phosphokinase were measured in 32 women during the last 3 weeks of pregnancy and, in a further 39 women, during and after labor. The serum creatinine increased from 61.9 +/- 0.9 to 69.8 +/- 1.8 mumol/l (mean +/- SEM) (P less than 0.05) in the third stage of labor and returned to normal by 72 h after delivery. The muscle creatine phosphokinase increased from 54 +/- 7 to 77 +/- 9.9 units (P less than 0.05) during the third stage and remained high (87 +/- 13.3 units) 72 h later. We conclude that these changes are due to muscle contraction and injury during delivery. PMID- 1892423 TI - A dermoid cyst of the paravaginal space. AB - We describes a patient with a dermoid cyst in the paravaginal space. The cyst recurred after repeated drainage procedures and became infected. The cyst was ultimately excised. PMID- 1892424 TI - Rupture of the uterus in labour. An unusual case followed with sonography. AB - In this case report a 27-year-old parturient with a previous caesarean section was diagnosed as having had a uterine rupture in labour. The diagnosis was based on the sonographic demonstration of considerable amounts of free fluid in the abdomen 2 h postpartum, and confirmed by finding fetal skin cells in this fluid. There was no hemorrhage and the fluid disappeared overnight. She was managed expectantly and made a rapid and full recovery. PMID- 1892425 TI - Intraamniotic infection with Haemophilus influenzae. Report of a case and review of the literature. AB - We report a rare case of intraamniotic infection with Haemophilus influenzae in a woman presenting with preterm premature rupture of membranes. Review of the literature identified 7 cases of intraamniotic infection with Haemophilus influenzae in patients with preterm premature rupture of membranes or with preterm labor and intact membranes. PMID- 1892426 TI - Photodynamic laser therapy of carcinomas--effects of five different photosensitizers in the colony-forming assay. AB - Photodynamic therapy (PDT) with laser radiation opens a new field in the treatment of malignancies. We evaluated the phototoxic effects of five different substances for photodynamic therapy in concentrations showing no systemic toxicity. We used gynecologic tumor cells and evaluated the photodynamic effects for cell growth in a colony-forming assay. For Indigocarmin we found a reduction in the colony-forming assay compared to the control group from 87% to 66% after irradiation at 50 mumol/l and 608 nm wavelength. "IR 132" showed a reduction in the colony-forming assay from 73% to 72% 50 mumol/l (590 nm). For the incubation of the HeLa cells with 50 mumol/l of "Sulfo-Phthalocyanin" we found a reduction of the colony-forming potential from 81% to 67% (595 nm). The most strikingly differences were found for the incubation and irradiation of Methylene Blue, showing a reduction from 77% to 16% caused by a toxic effect of the substance itself (5 mumol/l, 660 nm) and "Sulfo-Aluminium-Phthalocyanin" stained cells, which shows a reduction from 86% to 17% (50 mumol/l, 675 nm). We see the possibility of a photoactivation and cell devitalisation by "Sulfo-Aluminium Phthalocyanin" and laser radiation. A future clinical trial would seem justified. PMID- 1892427 TI - [Changes in virulence of Enterobacteriaceae in the presence of sub-inhibitory levels of antibiotics]. AB - The effect of subinhibitory concentrations of antimicrobial agents such as chloramphenicol, tetracycline, rifampicin and nalidixic acid on various factors of virulence in Shigella spp. and enteroinvasive colon bacilli was studied. It was shown that under such conditions changes took place in various events of the interaction with the epithelial cells, i.e. in adhesion, penetration, intracellular multiplication and transfers between contacting cells. The total effect of chloramphenicol resulted in increasing of the virulence while that of nalidixic acid, tetracycline and rifampicin resulted in its decreasing. PMID- 1892428 TI - [Sensitivity of Brucella melitensis to various antibiotics, drug preparations and their combinations]. AB - In vitro activity of 13 antibiotics and drug preparations as well as some of their combinations was studied with respect to Brucella melitensis. It was shown that the strains of B. melitensis were sensitive to sisomicin, amikacin, gentamicin, cefotaxime, rifaprim +, nitroxoline and trimethoprim. Variations in the doxycycline sensitivity depending on the strain were observed. The strains of B. melitensis were resistant to cephalexin, phosphomycin, chinoxydine, dioxydine and oxolinic acid. Combinations of sisomicin and trimethoprim at a ratio of 1:10 and sisomicin and nitroxoline at a ratio of 1:2 had a summation effect. PMID- 1892429 TI - [Sodium sulfapyridazine in new delayed-action bases for the treatment of bacterial conjunctivitis]. AB - Possible preparation of 10 per cent sodium sulfapyridazine ophthalmic drops containing aubazidan, a microbial polysaccharide, providing prolongation of the drops action and stability on the storage was studied. The pharmacokinetic studies showed that aubazidan which is a natural polymer provided high prolongation of the sulfapyridazine effect in the tissues of the anterior part of the eye in rabbits. The prolonged effect was similar to the previously observed effect of the solutions containing synthetic polymers such as 1 per cent polyacrylamide and polyvinyl . Satisfactory tolerance by the rabbit eye tissues of 6-fold daily instillations of the 10 per cent sodium sulfapyridazine solution with aubazidan for the observation period of 1 month was stated. When stored in vials the 10 per cent sodium sulfapyridazine ophthalmic drops with 0.5 per cent of aubazidan preserved the stability for 24 months with respect to the colour, transparency, viscosity, pH and drug content. It was demonstrated with using the agar diffusion method and Staphylococcus aureus, Proteus vulgaris, Escherichia coli and Pseudomonas aeruginosa as the test cultures that sodium sulfapyridazine completely preserved its antimicrobial activity in the presence of aubazidan. The data suggested that clinical trials of the 10 per cent sodium sulfapyridazine solution with 0.2-0.5 per cent of aubazidan were promising in prevention and therapy of bacterial conjunctivitis. PMID- 1892430 TI - [A method of determining the degree of bacteriuria and its detection using the Bioscreen system]. PMID- 1892432 TI - [The role of propionyl-CoA carboxylase in the biosynthesis of antibiotics]. PMID- 1892433 TI - [Pharmacokinetics of amphotericin B and its derivatives]. PMID- 1892431 TI - [Variability of ceftazidime pharmacokinetics in children with suppurative-septic diseases]. AB - Marked variability of the ceftazidime pharmacokinetics (Cmax and T1/2) was observed in 3 newborns and 2 infants with purulent septic infections. The patients were under complex treatment in a reanimation unit (artificial pulmonary ventilation, infusions). It was recommended to perform the treatment with monitoring the antibiotic plasma concentrations to prevent the drug failure because of the changes in the distribution and excretion patterns. The use of HPLC for the purpose is advisable. PMID- 1892434 TI - [Chemotherapy of AIDS: results and prospects]. PMID- 1892435 TI - [Non-traditional beta lactams--carbapenems, penems and monocyclic antibiotics]. PMID- 1892436 TI - [Antineoplastic activity of the higher fungus AG-1 (the Basidio- mycete class)]. PMID- 1892437 TI - [Structure of pentaene antibiotic lavendofuseomycin]. AB - By its UV spectrum lavendofuseomycin, a macrolide pentaene antibiotic, was referred to the subgroup of adeopentaenes with the spectral symmetrical patterns. The antibiotic contains a carbonyl, the end and 4 isolated double bonds and hemiketal ring. The molecule is lacking sugar. After the hydroantibiotic oxidation 2-methylhexadecane dicarboxylic and 4'-methyloctanoic acids were isolated. The antibiotic carbon skeleton was asserted on the basis of the mass spectral analysis of the products of the antibiotic complete reduction and the products of the antibiotic retroaldol cleavage. Determination of the position of the isolated double bonds, localization of chromophore, oxygen functions and the position of the amino group in the molecule resulted from investigation of the antibiotic azonolysis products. PMID- 1892438 TI - [The kallikrein-kinin system and allergy]. PMID- 1892439 TI - Dermatophagoides pteronyssinus specific IgM antibody and its complement activation in children with bronchial asthma. AB - Western blotting analysis and ELISA were used to examine Dp specific IgM abs in the sera and sputa of bronchial asthmatic and non-atopic children. With Western blotting Dp specific IgM abs were detected binding diffusely to high molecular weight (greater than 65 kD) components of Dp extracts and from the intensities of the staining of the sera the asthmatic children were divided into two groups: an intensive staining and a faint staining group. The non-atopic children showed still fainter staining than the latter group. ELISA titers of Dp specific IgM abs in the intensive staining group were significantly higher than in the faint staining group and the non-atopic children (p less than 0.01). Dp specific IgM abs in sputa were also detected more intensively in asthma than in non-atopy by Western blotting. The hemolytic complement activities of the fresh sera were consumed when they were incubated with Dp extracts at 37 degrees C. The degree of consumption was significantly higher in the intensive staining group than in the faint staining group and the non-atopic children (p less than 0.05). High molecular weight fractions of Dp extracts were responsible for this complement inactivation. From these results we suspected that Dp specific IgM abs might react with high molecular weight components of Dp to induce complement activation by the classical pathway and might cause chronic inflammatory changes in the respiratory mucosa. This chronic inflammation might emphasize IgE mediated asthmatic reactions to cause late phase reactions or chronic asthma. PMID- 1892440 TI - [Role of eosinophils in the late asthmatic response]. AB - The occurrence of late asthmatic response (LAR) is effectively prevented by corticosteroids, but not all by beta-adrenergic drugs. LAR is considered to be of great clinical and therapeutic importance and to be involved in the progression of bronchial asthma into a severe or even an intractable form. However the exact mechanism of the occurrence of LAR remains obscure in many respects. LAR is believed to be due to type I allergy. In guinea pigs, a positive bronchial inhalation challenge following passive sensitization with allogeneic antibody does not induce LAR or eosinophilic infiltration of lung tissue. This experimental fact led us to surmise that LAR would seem likely to be elicited in passively sensitized animals if pronounced eosinophilic infiltration can be induced concurrently and to conduct an experiment with conjoined inhalation of platelet activating factor (PAF). PAF, which has a chemotactic activity for eosinophils, was administered to passively sensitized animals in attempt to examine a role of eosinophils in LAR. A goodly number of animals developed LAR on additional PAF inhalation. These animals, when compared with those without LAR, showed a significantly larger proportion of eosinophils in BALF (p less than 0.05) with an upward tendency for the proportion of neutrophils. Histologically, there was noted a striking association between LAR and eosinophilic infiltration of the bronchial submucosa. These results suggest that anti-IgE antibody is deeply involved in the elicitation of LAR, stressing the importance of eosinophilic infiltration. PMID- 1892441 TI - [Studies of free theophylline in asthmatic patients]. AB - Total and free theophylline concentrations were examined by fluorescent immunoassay using serum from 48 asthmatic patients treated with sustained-release theophylline formulation. Total and free theophylline concentrations showed a good correlation. The mean % free theophylline (free theophylline concentration X 100/total theophylline concentration) was 44.7% in children and 43.6% in adults. The % free theophylline had no relation to age of the patients or total theophylline concentration. However, the % free theophylline increased correlatively when serum pH or albumin was decreased. As changes in free theophylline concentration influence therapeutic responses and side effects, an assessment of serum pH and albumin in patients treated with theophylline is necessary. PMID- 1892442 TI - [Evaluation of Hymenoptera hypersensitivity including large local reactions among forest administration workers in Gunma prefecture]. AB - We used a questionnaire to investigate Hymenoptera hypersensitivity in 715 forest administration workers in Gunma prefecture and measured venom specific IgE antibodies in those who had exhibited large local reactions (LLR). The results were as follows. 1) Almost all, i.e. 660 (92.3%), of the workers, including 156 (23.6%) hypersensitive workers, had been exposed to insect stings and 241 (36.5%) had experienced LLR. 2) Among the hypersensitive workers, 68.9% exhibited systemic reactions after having been stung no more than ten times and 18.2% experienced systemic reactions when they were stung for the first time. 3) About 60% of the hypersensitive workers had been stung on only one site when they exhibited systemic reactions. 4) An evaluation of venom specific IgE titer for the workers who experienced LLR revealed a relatively high rate of RAST positive results to yellow jackets (39.3%) and wasps (36.9%). PMID- 1892443 TI - [Simple allergen skin test device Multi skit (tentative name)]. AB - We have developed a device tentatively named Multi Skit (Mu), a simple allergen test device, in order to conduct the skin test safely, accurately and conveniently. The utility of this device was evaluated by determining how the results obtained by the intradermal test (In) and Mu were correlated with those obtained by IgE RAST (RA) in 65 AD patients. RA values concerning nine antigens were compared to results obtained by the In and Mu in terms of the positive and negative response coincidence rates, overall coincidence rates, and false positive and false-negative response rates. The correlation between RA data obtained from the literature and the results of the scratch test (Sc) was also evaluated. The results of In and RAST values showed no correlation regardless of the food antigen used. Mu and RAST values showed correlation with respect to all 4 food antigens except soy-bean, resulting in overall coincidence rates of 66.2 to 87.7%, which were higher than those concerning the Sc. With respect to false positive responses to environmental antigens, the rate obtained by Mu was higher than that by the Sc, but it was lower than that by the In. However, Mu was the most excellent test with respect to the other indices, i.e., positive and negative response coincidence rates, overall coincidence rates (73.9-89.2%) and false-negative responses. The mechanism of Mu makers it possible to minimize variations from one investigator to another, and the major drawback of all other skin tests. Mu is a safe and convenient screening skin test device which provides accurate and specific test results. PMID- 1892444 TI - [The oral Prausnitz-Kustner reaction in food allergies]. AB - The oral Prausnitz-Kustner (P-K) reaction was examined in 41 children suspected of IgE-mediated food allergy. The recipients were served by their mothers in this study. A positive reaction was observed in 9 children when used hen's egg, cow's milk, chicken, buckwheat, red-bean, salmon or common-dolphin. Among them, seven have had an anaphylactic skin reaction (systemic urticaria and/or angioedema) to the foods. The other two were babies who were fed only by the breast milk. Therefore, the oral P-K test may be useful for the diagnosis and the prediction of food-anaphylaxis. The sera that had the radioallergosorbent test (RAST) scores of 3 or greater were negative in the oral P-K reaction in 26 out of 36 tests, and the sera that showed the positive oral P-K reaction to buckwheat or chicken were zero in the RAST scores. These results suggest that a soluble substance (e.g., histamine-releasing factor) in addition to the IgE antibody might be involved in the oral P-K reaction, and that the RAST technique does not always detect the IgE antibody that recognizes the food antigens degenerated during the absorption in vivo. PMID- 1892445 TI - [The mite-free room (MFR) for the management of atopic dermatitis: living in the MFR improved first the itch and then the dermatitis]. AB - While there are increasing data supporting the view that mite allergen sensitivity is one of the major causes of atopic dermatitis (AD) as well as asthma, it is practically difficult to avoid house dust allergens as part of the management of AD. Therefore, we served a conditioned room in which mites were eliminated to the level less than 3 mites/m2, named mite free room (MFR) for experimental treatment of AD to evaluate the possible therapeutic effect of the mite-free condition. Thirteen relatively severe patients with high-IgE RAST score to the mite allergens were treated with night time admission to the MFR without disturbing their social activities in the day time. Our MFR treatment gave eleven of the thirteen patients relief from itch and dermatitis within 2 to 3 weeks, yet they stayed average only 11 hours a day in the MFR. These results may provide a possible candidate in the treatment of AD instead of topical and/or systemic medicines of which prolonged usage is sometimes associated with adverse side effects. PMID- 1892446 TI - [Clinical effect of hypoallergenic rice (HRS-1) in atopic dermatitis. HRS-1 Research Group]. AB - The usefulness of hypoallergenic rice (HRS-1) was clinically evaluated in 43 patients with severe atopic dermatitis (AD), who were suspected of having rice allergy, in collaboration with 13 hospitals. The patients were fed with HRS-1 instead of eliminating both regular rice and wheat from their daily diet. AD area and severity index (ADASI) was calculated as an indicator of the degree of cutaneous symptoms. Significant decrease of ADASI were observed in the 2nd and 4th week and at the end of the replacement therapy (5.6 weeks on average). On final evaluation, 74% of the patients tested showed "moderate" to "remarkable" improvement, and in 53% of the patients HRS-1 resulted in a "moderate" to "remarkable" reduction in the dosage and the grade of potency of the steroid ointment concomitantly used for the treatment. Finally, HRS-1 was evaluated as "useful" to "very useful" as the elimination diet in 70% of the patients. PMID- 1892447 TI - [Tumor necrosis factor in sputa of patients with bronchial asthma on exacerbation]. AB - TNF is a cytokine recently implicated as an important inflammatory mediator. TNF concentrations in sputa from 13 patients with bronchial asthma on exacerbation and 12 patients with chronic obstructive pulmonary disease were measured. After sonication, the sputa were centrifuged. The supernatants were assayed for the presence of TNF by use of an enzyme-linked immunosorbent assay. TNF was detected in all patients with bronchial asthma (1783 +/- 420 pg/ml), while low values of TNF were detected in only 5 of the 12 COPD patients. It is suggested that TNF is involved in airway inflammation in bronchial asthma. PMID- 1892449 TI - Anatomo-pathological studies on alcoholic dementia: a review and up to date research. AB - Neuropathological studies of cerebral disorders in alcoholics which started by means of macroscopic observation have issued many important articles until now. However, we can not yet stretch out the essential core of alcoholic dementia. Plenty of animal experiments also suggest some possibility fo neurotoxicity by ethanol but do not offer a definitive resolution. Moreover, there is the strict criticism concerning neuropathological evidence on alcoholic dementia. Nevertheless, we know that there are some alcoholics who have no evidence of Wernicke-Korsakoff syndrome, but manifest persistent cerebral impairment after long-term heavy drinking. Under such circumstances it might be necessary to consider and study cerebral disorders in alcoholics, particularly relating to subcortical lesions. Pathomorphological investigations in our laboratory have put forward some significant findings. PMID- 1892448 TI - [Clinical concept of alcoholic dementia]. AB - Intellectual deterioration, changing in behavior and affect are often seen in association with long continued and heavy alcohol ingestion and such deteriorated states of patients are called alcoholic dementia. A large number of investigators have attempted to designate clinical concept of alcoholic dementia throughout the centuries and many kinds of term like as alcoholic pseudo-paralysis, alcoholic mental deficiency and alcoholic deterioration, etc, have been submitted since the beginning of 19th century. Numerous psychometric studies have indicated cognitive impairment and memory disturbance in chronic alcohol abusers and moreover brain PEG and CT-scan studies have shown sulcal widening and enlarged ventricles to be common in alcoholics. However, alcoholic dementia is hard to classify as a distinct disorder caused by alcoholic ingestion. The reason is lack of specific findings, both clinical and histopathological, like as Wernicke-Korsakoff syndrome and other nutritional disorders in alcoholics. Victor, M. describes in his work the majority of patients who have come to autopsy with the clinical diagnosis of primary alcoholic dementia have shown the lesions of the Wernicke Korsakoff syndrome and he postulates alcoholic dementia is heavily contaminated with burned-out Wernicke-Korsakoff disease. The clinical and pathological observations presented by this time represent alcoholic dementia is a residual category for cases in which there are severe impairment of intelligence with marked deterioration of personality following prolonged and heavy drinking. PMID- 1892450 TI - [Problem drinkers among high school students in Japan]. AB - In Japan, an increase in the consumption of alcohol by young people has been noted. This survey on drinking problems was performed on 1062 students of second year high school in 1990 using the Adolescent Alcohol Involvement Scale (AAIS). The results revealed that among all of the survey subjects of both sexes, 21.4% were abstainers, 4.2% normal adolescents, 60.9% non-problem drinkers, 12.6% alcohol misusers and 0.9% alcoholic-like drinkers. A high alcohol consumption rate and high percentages of those with drinking problems were observed among high school students. Students who used other addictive substances (i.e., smoking or thinner inhalation) reported significantly higher AAIS scores than those who didn't. Similarly high mean AAIS scores were found among students with family problems such as drinking parents or broken homes than those without this problem. Alcohol misusers and alcoholic-like drinkers accounted for 14.2% of males and 12.7% of females. In a survey performed 10 years previously on high school students, no alcoholic-like drinkers were found and only 1% were alcohol misusers. These results indicated that problem drinkers have dramatically increased among Japanese high school students in the last 10 years. PMID- 1892451 TI - Glycolipids in rat cochlea. AB - In recent years, the functions of glycolipids have been intensively studied. Before the research of the roles of glycolipids in the inner ear, it seemed to be necessary to demonstrate the composition of glycolipids at first. Therefore, rat cochlea has been examined for glycolipid composition in the present study. Glycolipids extracted from 200 cochlea samples were separated into neutral and acidic glycolipid fractions. Each fraction was analyzed by thin-layer chromatography. The neutral glycolipid was almost exclusively galactosylceramide (cerebroside) with trace amounts of globoside and unidentified glycolipids. In acidic glycolipids, sulfated galactosylceramide (cerebroside sulfate) was most abundant. Of the gangliosides (sialic acid-containing glycolipids), ganglioside GM3 (51.8%) was the predominant component, and GM2 (6.0%), GM1 (8.8%), GD3 (10.7%), GD1a (8.7%), GD1b (5.9%), and GT1b (3.6%) were also detected. In addition to these, rat cochlea also contained several, minor, unidentified gangliosides. This pattern of the cochlear acidic glycolipids is very similar to that of the renal acidic glycolipids. This finding seems to be very interesting when considering that the toxic side effects of aminoglycosides occur only in the kidney and the inner ear. PMID- 1892452 TI - A case of eosinophilic granuloma in the temporal bone. AB - The following case reports a 4-year-old boy with a solitary eosinophilic granuloma in the right temporal bone. The patient complained of an inflammatory tumor in the right external ear canal. The histopathological diagnosis made based on the first specimen of the tumor in the right ear canal was foreign body granuloma. A polyp developed again in the right ear canal with postauricular swelling. Computerized tomography of the skull at that time showed an osteolytic defect in the right temporal bone filled with soft tissue. Diagnosis was established by finding of the presence of Birbeck granules in Langerhans histiocytes by electron microscopy. PMID- 1892453 TI - Differential transnasal pressure in anterior and posterior rhinomanometry. AB - Transnasal differential pressures during spontaneous breathing through an artificial nasal model were measured using anterior and posterior types of rhinomanometry by Rhinorheograph MPR-1100 manufactured by Nihon Kohden Co., Ltd. for comparing postnasal pressures at the nasopharynx with those at the nostril. No significant differences between postnasal pressures at the nasopharynx and at the nostril were found at 0.25, 0.5 liter/s, or the peak flow point on the pressure/flow relation curve. Application of the Ohm's Law equation for parallel resistors to nasal airflow resistance seems to be a more important problem than the differences resulting from the postnasal pressure sampling procedures in the anterior and posterior methods. PMID- 1892454 TI - Neurofibroma of the hypopharynx: a case report. AB - A 45-year-old female patient with a neurofibroma of the hypopharynx is reported. She had complained of swallowing discomfort for 3 months. Indirect laryngoscopy showed an oval tumor with a smooth surface in the posterior wall of the hypopharynx. Xeroradiography was effective for defining the tumor. Removal of the tumor was performed by an infrahyoid horizontal pharyngotomy under general anesthesia. The tumor had an indistinct capsule. The nerve from which the tumor originated was not clear. Histologically, the tumor was diagnosed as neurofibroma. The patient had no other neurogenic tumor and has been well without recurrence after the surgery. PMID- 1892455 TI - Carcinoid tumor of the larynx. AB - Carcinoid tumor of the larynx is a rare neoplasm. Two cases of laryngeal carcinoid tumor are reported and the relevant literature is reviewed. One patient was an 82-year-old male who complained of odynophagia. The tumor was located on the left arytenoid and neck metastasis were present when he died 3 years after surgery. The other patient was an 82-year-old male who complained of hoarseness. His tumor was located in the left ventricle. Bone metastasis was detected one month after surgery and he died of distant metastasis two months following surgery. A review of the literature showed that carcinoid tumors of the larynx are aggressive and malignant, with distant metastasis being the most common cause of death. This tumor is unresponsive to radiotherapy and chemotherapy, so adequate surgical excision remains the only effective treatment. PMID- 1892456 TI - Pathological changes of hyperphonated cat vocal folds. AB - To investigate the pathological changes of hyperphonated vocal folds 15 cats were used and over-cry was induced by mechanical stimuli. The longest experiment time was 15 weeks. All of the larynges were taken and the vocal folds were examined grossly and microscopically. The results were as follows: 1) liquid exudate accumulation beneath the epithelium developed in all of the experimental animals; 2) thickening of the epithelium was noticed in cats which had hyperphonated for more than 4 weeks; 3) acute laryngitis occurred in three cats. PMID- 1892457 TI - Histological study of atelocollagen infused into the human vocal cords. AB - There have been only three case reports of histological study on injection of atelocollagen into the human vocal cords, and none of these have indicated foreign body reaction. We histologically examined the larynx of a 70-year-old man, which had to be excised 44 days after infusion of atelocollagen into the vocal cords. The atelocollagen infused was found to have been replaced with the collagen of host cells, but no foreign body reaction was observed. As in conventional reports, the histoaffinity of atelocollagen was confirmed. PMID- 1892458 TI - Bio-feedback and the yawning breath pattern in voice therapy: a clinical trial. AB - A breathing technique, or effective breath method is important for both singers and speakers for effective vocalization, and also useful for helping people with a voice problem. Here a diaphragm support breath pattern was used in voice therapy for patients with vocal nodules, recurrent laryngeal nerve paralysis, and incomplete glottal closure. Singing teachers use a technique, called the diaphragm breath support. This is called the yawning breath pattern (YBP) in our voice clinic and is used in teaching the patients with some kinds of voice disorder. In order to correct patients' breath pattern, an equipment system was designed to check their breath patterns conveniently in voice therapy practice. A respiratory kinematic sensor which connected to a TV monitor was attached to the patients' rib cage near the diaphragm, and by bio-feedback, patients could observe and adjust their breath pattern to the desired pattern during vocalization. In each of the 10 outpatient sessions, the patients performed for 20 to 30 min, and were instructed to practice at home for 3 or more times daily. The YBP method was applied to 91 patients, 17 males and 74 females, with ages ranging from 17 to 79 years. Of the 91 patients 41 had vocal nodules, 20 had recurrent laryngeal nerve paralysis and 30 had incomplete glottal closure associated with chronic laryngitis and sulcus vocalis. Most of the patients could master the YBP technique successfully. The higher the patients' ability to master the YBP was the better the results of both voice tests and subjective evaluation. The scientific background of the YBP method and its clinical effects in voice therapy was reviewed. PMID- 1892459 TI - Actinomycosis of the larynx. AB - Actinomycosis is a disease characterized by a chronic suppurative and granulomatous process which tends to form multiple pyogenic draining sinus tracts. The most common site in which it occurs is the cervico-facial region, especially in the submandibular area. The exudates from the fistulous tracts usually contain yellow granules known as "sulfur granules," which can be considered as a hallmark of actinomycosis. We report a rare case of laryngeal actinomycosis which occurred in a 68-year-old male who had been irradiated 8 years before due to laryngeal carcinoma. During the admission, the patient was also diagnosed as being a myelodisplastic syndrome carrier. The patient was treated successfully with penicillin 10 million IU administered daily over 40 days. The etiologic agents, predisposing factors, diagnostic procedures, and available treatments are discussed, and the pertinent literature is reviewed herein. PMID- 1892460 TI - Branchial cleft (pouch) anomalies: a review of 42 cases. AB - A retrospective review was made of the medical records of 42 patients, who had had branchial cyst, sinus, or fistula, and who had been seen and treated at our hospitals. Three of these lesions were considered to have originated from the first branchial cleft, 36 from the second branchial cleft and/or pouch, and 3 from the fourth branchial pouch. There were no sex and side of presentation differences in the second branchial anomalies. However, the first branchial anomalies occurred predominantly in females, and the fourth branchial anomalies were predominantly left-sided. Pathological findings were of squamous epithelium and subepithelial lymphoid follicles in most branchial remnants. Skin, adenexa, and cartilage were observed in two first branchial cleft sinuses (Work's classification Type II). Columnar epithelium (respiratory type) was observed in a second branchial pouch cyst and a second branchial fistula. All the patients with first or fourth branchial anomalies had previous infections with incision and drainage procedures, whereas only two out of 36 patients with second branchial anomalies had had previous incision procedures. All patients after complete removal of branchial anomalies have no recurrence. PMID- 1892461 TI - Pinch grafting of the open mastoid cavity. AB - Secondary pinch skin grafting was performed on the mastoid cavities to promote healing of the mastoid wound after ear surgery using the open technique. Pinch grafts (multiple small grafts of the epidermal layer) were transplanted in 20 patients, soon after the mastoid cavities were covered with healthy granulation tissue in a mean of 28.5 days after the initial surgery. The grafts adapted well in 18 of the 20 patients. Epidermization was complete in a mean of 11.1 days after grafting, that is, within 40 days after the initial ear surgery. On the other hand, epidermization in 10 cases without grafting was completed in a mean of 83.3 days after the ear surgery. Thus, the pinch grafts reduced healing time by more than 40 days. The secondary application of pinch grafting was beneficial for healing of exposed mastoid cavities caused by use of the open technique tympanoplasty or radical mastoidectomy. PMID- 1892463 TI - Overview: the major histocompatibility complex and insulin dependent diabetes mellitus. PMID- 1892464 TI - Genetics of diabetes. Part I. PMID- 1892462 TI - Calcium distribution and mobilization in single rat parotid acinar cells investigated by digital imaging microscopy. AB - The intracellular distribution and mobilization of cytosolic free calcium in single rat parotid acinar cells was analyzed by a digital imaging microscope equipped with a microspectrofluorometer, using calcium-sensitive dye fura-2. In the resting state, intracellular distribution of cytosolic free calcium concentration ([Ca2+]i) was heterogeneous: [Ca2+]i in the nuclear and perinuclear region was usually higher than that in the cytoplasm. By Ca(2+)-ionophore ionomycin and muscarinic agonist carbachol stimulation in the presence of 1 mM extracellular Ca2+, [Ca2+]i increased markedly and the gradient of [Ca2+]i between the nuclear region and the cytoplasm decreased. In ionomycin stimulation, [Ca2+]i increased homogeneously and this homogeneous increase was irreversible. In carbachol stimulation the gradient of [Ca2+]i between the nuclear region and the cytoplasm obviously reappeared within 2 min. By carbachol stimulation in the absence of extracellular Ca2+ (added 1 mM EGTA), [Ca2+]i returned to the prestimulation level after the initial transient increase. The distribution of [Ca2+]i also returned approximately to the prestimulation state. The gradient of [Ca2+]i between the nuclear region and the cytoplasm did not disappear even when [Ca2+]i elevated at the peak value. PMID- 1892465 TI - HLA population genetics. AB - The HLA system has been extensively studied from an evolutionary perspective. The region contains a number of closely linked genes whose products control a variety of functions concerned with the regulation of immune responses. In addition, the genetic predisposition to over 40 diseases maps to this region. A number of observations indicate that strong selection is acting on the HLA region, including its extensive polymorphism with very even allele frequencies, the preferential occurrence of high levels of variability at positions critical to antigen recognition, the great age of alleles and the patterns of linkage disequilibrium among loci. The form of the selection is unknown. Although balancing selection is a strong candidate, it seems unlikely that only one selective mechanism is operating in this complex multigene family region. Mutation, recombination and gene conversion all contribute to the generation of HLA variability. The apparent great age of many HLA alleles revealed by phylogenetic analysis suggests that the absolute rate of production of new variants is not high. Detailed studies of population and evolutionary features of the HLA region are necessary for an informed discussion of the evolution of disease predisposing genes and epitopes, and of complex multigene families. PMID- 1892466 TI - Genetics of diabetes. Lessons from family studies. PMID- 1892467 TI - Genetics of diabetes. Studies of MHC haplotypes by pulsed field gel electrophoresis. PMID- 1892468 TI - Cross-ethnic group comparisons of HLA class II alleles and insulin dependent diabetes mellitus. AB - HLA class II associations with IDDM in populations of non-Caucasoid origin can provide important insights into the nature of the HLA and disease association. Firstly, HLA class II alleles that are rare in Caucasoids but common in other populations can be assessed for their contributory role in IDDM. Secondly, the different HLA class II gene linkage arrangements in different populations can help map the IDDM susceptibility determinants. This chapter reviews studies of HLA class II associations with IDDM in Asian Indians, Chinese, Japanese, Africans and black Americans. Most of these studies have been based on HLA-DR serology. However, DNA analyses, based on restriction fragment length polymorphism, sequence specific oligonucleotide hybridizations of polymerase chain reaction products and DNA sequencing, have made clear the identity of genes contributing to susceptibility or resistance to IDDM in populations of non-Caucasoid origin. DNA sequence analysis of the variable regions of the HLA-DQA, DQB and DRB genes has revealed at least eight alleles at HLA-DQA, 13 at HLA-DQB and 34 at HLA-DRB1. This chapter correlates HLA-DR and DQ allelic diversity with inherited predisposition to IDDM on a global basis. IDDM is strongly associated with the serological specificities of HLA-DQ, rather than with particular amino acid substitutions in class II alleles. DQw8 has a high risk for IDDM, DQw4, DQw5 and DQw9 have a lesser risk, while DQw6 and DQw7 are protective in IDDM. DQw2 is permissive for IDDM, depending on the presence of other HLA class II alleles. Increased heterozygosity at HLA is observed in Oriental patients, as it is in Caucasoid IDDM patients. The nature of this synergism is examined in terms of possible interactive effects between DQA and DQB alleles or DRB and DQB alleles; both effects could be operating. The conclusion from this genetic analysis is that molecular mimicry at HLA-DQ, with either foreign or autoantigens, may be an important mechanism in IDDM. Additionally, the anomalous role of DQw2 in IDDM suggests that a further mechanism, such as T cell activation, may control the ability to mount an immune response against autoantigens. Further studies, possibly with transfectant cell lines, are necessary to clarify the functional role of HLA class II genes in IDDM. PMID- 1892470 TI - Genetics of diabetes. Part II. PMID- 1892469 TI - Genetics of diabetes. Trans-racial gene mapping studies. AB - A major component of inherited susceptibility to IDDM is associated with one or more loci in the MHC. Identification of the primary susceptibility genes has been complicated by the low frequency of recombination, i.e. linkage disequilibrium, within the MHC. It is difficult to distinguish whether a detected genetic association with the disease is primary, or secondary due to linkage disequilibrium with an allele at another locus which is directly predisposing. During the evolution of different races, however, recombination within the MHC has occurred and population-specific MHC haplotypes exist. Primary susceptibility allels should be associated with disease in all racial groups, regardless of genetic background. It is unlikely that disease associations secondary to linkage disequilibrium will be consistent in these groups. This chapter reviews the known associations of candidate class II susceptibility alleles with IDDM in the five largest racial groups; white Caucasians, Asian Indians, Negroids, Japanese and Chinese. These trans-racial studies suggest that the DQ molecule has a primary role in predisposition to IDDM. There are consistent findings of a positive association with the DQA1*0301 allele and negative associations with the DQB1*0602 and DQB1*0603 alleles. These two alleles differ by a single codon and so the encoded DQ beta chains are likely to have similar functions. DR4 associated susceptibility is associated with the DQA1*0301 allele in all races tested so far but this allele cannot be the only susceptibility factor on this haplotype. The identity of the DR3-associated susceptibility factor remains unclear but the DQB1*0201 allele is a candidate. If DQB1*0201 is involved, the existence of a protective factor on the neutral DR7-DQB1*0201 haplotypes is indicated. Analysis of DR9 associated susceptibility implicates a non-DR/DQ predisposing factor. PMID- 1892471 TI - Insulin dependent diabetes mellitus susceptibility or protection may be determined by certain HLA-DQ molecules. AB - On the basis of our own studies and those of others, we suggest that several DQ molecules may be involved in IDDM susceptibility (Table 2). Our studies suggest that these DQ molecules may be encoded both when the DQA1 and DQB1 genes are in cis or trans position. A common denominator of several of these IDDM susceptibility molecules is that they have a non-Asp amino acid at DQ beta chain residue 57. Our studies demonstrate that this residue may be an important residue for peptide presentation to T cells. PMID- 1892472 TI - Genetics of non-insulin dependent diabetes mellitus. AB - It is probable that NIDDM has a multifactorial origin in which environmental factors hasten the progression of the disease in genetically predisposed individuals. The importance of the genetic contribution to NIDDM has been established by the study of certain inbred populations, the almost 100% concordance of disease in monozygotic twins and by familial clustering. However, progress in identifying specific genetic factors involved in NIDDM has been slow and no consistent evidence has emerged supporting a major aetiological role for any of the genes so far studied. This may be due in part to methodological problems encountered in the identification of such disease susceptibility genes. PMID- 1892473 TI - Genetics of non-insulin dependent diabetes mellitus in 1990. AB - Family studies suggest a strong genetic component in the aetiology of non-insulin dependent diabetes (NIDDM), with evidence for a major gene of co-dominant or dominant effect. A gene-dosage effect, whereby diabetes develops earlier in people with two susceptibility genes than in those with one susceptibility gene is likely. The search for the diabetes gene has led to the cloning and characterization of many genes involved in controlling glucose homeostasis. These include the insulin, insulin receptor, glucose transporter, amylin and glucokinase genes. Molecular techniques have permitted rapid screening of these genes in NIDDM patients and controls. There is now a rather contradictory genetic literature for NIDDM, with weak disease associations reported and refuted for most candidate genes. However, pedigree analyses and DNA sequencing of available candidate genes and their regulatory regions have failed to implicate any of these in the common form of diabetes, NIDDM. Methodical application of random clones in well-defined NIDDM families may be the strategy of choice in finding the NIDDM genes, given the wide range of genes potentially involved in the glucose and lipoprotein metabolic disturbances seen in NIDDM. PMID- 1892474 TI - Structure and evolution of the actin crosslinking proteins. AB - The actin crosslinking proteins exhibit marked diversity in size and shape and crosslink actin filaments in different ways. Amino acid sequence analysis of many of these proteins has provided clues to the origin of their diversity. Spectrin, alpha-actinin, ABP-120, ABP-280, fimbrin, and dystrophin share a homologous sequence segment that is implicated as the common actin binding domain. The remainder of each protein consists of repetitive and non-repetitive sequence segments that have been shuffled and multiplied in evolution to produce a variety of proteins that are related in function and in composition, but that differ significantly in structure. PMID- 1892475 TI - C-CAM (cell-CAM 105)--a member of the growing immunoglobulin superfamily of cell adhesion proteins. AB - Cell recognition and adhesion, being of prime importance for the formation and integrity of tissues, are mediated by cell adhesion molecules, which can be divided into several distinct protein superfamilies. The cell adhesion molecule C CAM (cell-CAM 105) belongs to the immunoglobulin superfamily, and more specifically is a member of the carcinoembryonic antigen (CEA) gene family. C-CAM can mediate adhesion between hepatocytes in vitro in a homophilic, calcium independent binding reaction. The molecule, which occurs in various isoforms, is expressed in liver, several epithelia, vessel endothelia, platelets and granulocytes and its expression is dynamically regulated under various physiological and pathological conditions. It is proposed that C-CAM in different cells and tissues plays different functional roles, where the common denominator is membrane-membrane binding. PMID- 1892476 TI - Growth cones: the mechanism of neurite advance. AB - Growth cones are the highly motile structures found at the tips of growing axons and dendrites (neurites), which extend from neurones, during the development of the nervous system. They function both as detectors and transducers of extrinsic guidance cues and as regions where the neurite assembly, advance cannot occur. Assembly of the neurite cytoskeleton in growing neurites chiefly involves microtubule assembly at the growth cone. Some of the factors that may influence microtubule assembly in growth cones are becoming apparent and include post translational modification of tubulin itself and microtubule associated proteins, particularly tau and MAP1B. PMID- 1892477 TI - The transactivator GAL4: co-activators, adaptors and chromatin. PMID- 1892478 TI - Stabilization of post-translational modification of microtubules during cellular morphogenesis. AB - This review discusses the possible role of alpha-tubulin detyrosination, a reversible post-translational modification that occurs at the protein's C terminus, in cellular morphogenesis. Higher eukaryotic cells possess a cyclic post-translational mechanism by which dynamic microtubules are differentiated from their more stable counterparts; a tubulin-specific carboxypeptidase detyrosinates tubulin protomers within microtubules, while the reverse reaction, tyrosination, is performed on the soluble protomer by a second tubulin-specific enzyme, tubulin tyrosine ligase. In general, the turnover of microtubules in undifferentiated, proliferating cells is so rapid that the microtubules accumulate very little detyrosinated tubulin; that is, they are enriched in tyrosinated tubulin. However, an early event common to at least three well studied morphogenetic events--myogenesis, neuritogenesis, and directed cell motility--is the elaboration of a polarized array of stable microtubules that become enriched in detyrosinated tubulin. The formation of this specialized array of microtubules in specific locations in cells undergoing morphogenesis suggests that it plays an important role in generating cellular asymmetries. PMID- 1892479 TI - 55th annual meeting, American College of Rheumatology. Boston, Massachusetts, November 17-21, 1991. Abstracts. PMID- 1892480 TI - Rice bran oil lowers serum total and low density lipoprotein cholesterol and apo B levels in nonhuman primates. AB - The hypolipidemic response of rice bran oil (RBO) was investigated in nonhuman primates fed semi-purified diets containing blends of oils which included RBO at 0-35% Kcals as dietary fat. The studies demonstrated the following: (a) the degree of reduction of serum total cholesterol (TC) and low density lipoprotein cholesterol (LDLC) was highly correlated with initial serum cholesterol levels of the monkey on the stabilization diet; (b) the content of rice bran oil in the diet was the predominant factor influencing serum TC, LDLC and apoB causing up to a 40% reduction in LDLC without affecting high density lipoprotein cholesterol (HDLC) when RBO was the sole dietary oil fed; (c) the cholesterol-lowering capabilities of RBO were not explained by its fatty acid composition. These studies suggest that RBO may be an additional vegetable oil which lowers serum cholesterol levels by unique mechanisms which will require further study. PMID- 1892481 TI - Influence of hydrolysis on plasma homocysteine determination in healthy subjects and patients with myocardial infarction. AB - After acid hydrolysis, mean plasma homocysteine concentrations, measured as homocysteine disulphides, of about 1000 and 40 mumol/l have recently been reported in 26 survivors of myocardial infarction and 26 matched control subjects, respectively. This finding contrasts sharply with those more than 50 times lower total homocysteine concentrations found by other research groups in non-hydrolysed plasma from survivors of myocardial infarction. Using the same hydrolysis conditions, we could not detect any homocysteine disulphides in plasma hydrolysates from 9 survivors of myocardial infarction and 10 healthy subjects, who had mean total homocysteine concentrations in non-hydrolysed plasma of 16.9 +/- 6.5 and 15.8 +/- 10.3 mumol/l, respectively. The chromatograms contained several peaks, probably representing peptides, which disappeared with more complete hydrolysis and which might have been misinterpreted as homocysteine disulphides in the reported study. Only after reduction of disulphides and by using a sulphydryl-selective extraction procedure were we able to determine mean homocysteine concentrations in hydrolysed plasma to be 26.2 +/- 7.9 mumol/l in the survivors of myocardial infarction and 24.5 +/- 12.2 mumol/l in the healthy reference subjects. Thus, we could not confirm that survivors of myocardial infarction have homocysteine concentrations that are many times higher than found in healthy subjects. PMID- 1892482 TI - Asymptomatic hyperglycemia and cardiovascular risk factors in the elderly. AB - We studied the levels of cardiovascular risk factors in a population sample of 511 men and 920 women aged 65-74 years and living in East Finland. Altogether 312 men and 515 women had normal glucose tolerance, 84 men and 158 women impaired glucose tolerance (IGT), 33 men and 59 women newly diagnosed non-insulin dependent diabetes (NIDDM) detected at the survey, and 82 men and 188 women previously diagnosed NIDDM. Subjects with IGT or newly diagnosed NIDDM had higher levels of total triglycerides and apolipoprotein B and lower levels of HDL cholesterol and apolipoprotein A1 than subjects with normal glucose tolerance, similarly as in previously diagnosed NIDDM. Furthermore, subjects with IGT or newly diagnosed NIDDM were more obese, had higher waist-hip ratio, and more frequently hypertension than subjects with normal glucose tolerance. Thus, asymptomatic hyperglycemia in the elderly is not a benign phenomenon, but is associated with similar adverse changes in cardiovascular risk factors as in middle-aged subjects. PMID- 1892483 TI - Platelet secreted lipoprotein-like particle is taken up by the macrophage scavenger receptor and enhances cellular cholesterol accumulation. AB - Enhanced macrophage cholesterol accumulation is associated with foam cell formation in the atherosclerotic lesion. Since platelet activation plays an important role in atherogenesis, we questioned whether products released from activated platelets could affect macrophage cholesterol metabolism. The addition of platelet-conditioned medium (PCM, obtained from collagen activated platelets) to a J-774 macrophage cell line, enhanced cellular cholesteryl ester content by 32%. The cholesterol esterification rate was also increased by 29%. Pre-loading the macrophages with cholesterol by incubation with acetyl-LDL, resulted in a further elevation of 48% in PCM-mediated cholesterol esterification. Possible mechanisms for the enhanced cholesterol esterification by J-774 macrophages following incubation with PCM include increased cholesterol influx and/or decreased cholesterol efflux (These cells were recently shown not to synthesize cholesterol). However, both increased uptake of PCM cholesterol by the macrophages as well as increased cellular cholesterol efflux (by 22%) were noted. The enhancement of cholesterol esterification by PCM was competitively inhibited by fucoidin and polyinosinic acid, implicating PCM binding to the scavenger receptor. This was further evidenced by the observations that apolipoprotein E which reduces cellular uptake via the scavenger receptor but not via the LDL receptor, also inhibited the effect of PCM, whereas IgG C-7, the LDL receptor antibody, did not alter the effect of PCM. Lysosomal involvement in the cellular processing of PCM was observed since PCM activity was inhibited by the lysosomal inhibitor, chloroquine. Partial purification of PCM by gel filtration revealed that the cholesterol component was associated with both phospholipids and proteins in a lipoprotein-like particle. Delipidation of PCM resulted in its inactivation but both heat treatment and tryptic digestion of PCM, revealed that the protein (and not only the cholesterol) component was also essential for the effect of PCM on cellular cholesterol esterification. Furthermore, PCM prepared from platelets of a patient with Gray Platelet Syndrome that lack platelet alfa granules (which contain platelet specific proteins), failed to enhance cholesterol esterification. These results demonstrate that lipoprotein-like particles released during platelet activation can interact with the macrophage scavenger receptor thus leading to enhanced cellular cholesterol accumulation. PMID- 1892484 TI - Effects of probucol on plasma lipoprotein subfractions and activities of lipoprotein lipase and hepatic triglyceride lipase. AB - The effects of 12 weeks treatment with probucol on plasma lipoprotein subfraction levels and on LPL and HTGL activities were investigated. Plasma VLDL-C, VLDL-TG, VLDL-apo B levels were not changed. Probucol significantly reduced plasma IDL-C and IDL-apo B levels by 26.7% and 23.8%, respectively. Plasma cholesterol and apo B levels of large light LDL (LDL1) were decreased significantly by 27.8% and 23.2% by probucol treatment. Plasma cholesterol and apo B levels of small heavy LDL (LDL2) remained unchanged. Probucol markedly reduced plasma HDL2 levels. The reduction rates of plasma TC, TG and apo A-I levels of HDL2 were 43.0%, 43.6% and 47.0%. Probucol significantly decreased HDL3-C and HDL3-apo A-I levels by 18.0% and 19.2%. LPL activities in the post-heparin plasma were decreased significantly from 2.53 +/- 0.71 mumol free fatty acids (FFA)/ml/h to 1.71 +/- 0.71 mumol FFA/ml/h by probucol while HTGL activities remained unchanged. We conclude that probucol suppresses LPL activity and decreases plasma IDL, LDL1 and HDL2 levels due to disturbances of VLDL conversion to LDL1 via IDL and of HDL3 conversion to HDL2. PMID- 1892485 TI - Hypolipidemic effects of NB-598 in dogs. AB - NB-598, a new inhibitor of mammalian squalene epoxidase, was found to be a potent inhibitor of microsomal squalene epoxidase from dog liver. Hypolipidemic effects of NB-598 were compared with those of simvastatin (MK-733, a 3-hydroxy-3 methylglutaryl coenzyme A reductase inhibitor) in dogs. NB-598 was found to decrease serum total cholesterol levels and increase serum squalene levels in a dose-dependent manner. MK-733 decreased serum total cholesterol and squalene levels. Both NB-598 and MK-733 decreased all classes of lipoprotein cholesterol, and they decreased low density lipoprotein cholesterol most potently. Both drugs decreased phospholipid levels in parallel with cholesterol levels. NB-598 also decreased triacylglycerol levels. After termination of drug administration, these levels returned to the control levels. The potency of NB-598 is thought to be as great or greater than that of MK-733. Moreover, NB-598 increased squalene concentrations in the feces and gallbladder bile, but it did not affect neutral sterol and bile acid concentrations. NB-598 did not affect the lithogenic index. PMID- 1892486 TI - Comparison of the mitogenic activity of angiotensin II and serotonin on porcine arterial smooth muscle cells. AB - We have investigated the growth promoting activities of two potent vasoactive substances, serotonin and angiotensin II (AII), on cultured porcine aortic smooth muscle cells (ASMC), using a defined serum-free medium. Serotonin (30 nM to 30 microM) stimulated ASMC DNA synthesis both alone and in combination with platelet derived growth factor (PDGF) and epidermal growth factor (EGF). Serotonin-induced DNA synthesis was significantly inhibited by ketanserin (5-hydroxytryptamine-2 (5HT-2) receptor antagonist). AII (3-10 nM) failed to stimulate ASMC DNA synthesis directly, either alone or in combination with PDGF or EGF. Since both serotonin and AII were found to activate phosphatidylinositol turnover and are reported to mobilise intracellular calcium, it is apparent that these events alone are insufficient to stimulate ASMC mitogenesis. PMID- 1892487 TI - Familial defective apolipoprotein B-100: haplotype analysis of the arginine(3500) ---glutamine mutation. AB - Familial defective apolipoprotein B-100 (FDB) is a recently identified, dominantly inherited genetic disorder, which leads to an increased serum level of low density lipoprotein (LDL) cholesterol with reduced affinity for the LDL receptor. It is postulated that this disorder results from a G to A mutation at nucleotide 10,708 in exon 26 of the apo B gene creating a substitution of glutamine for arginine in the codon for amino acid 3500. To investigate whether recurrent mutation has contributed to the high frequency of FDB, we have conducted a haplotype analysis in previously reported and newly detected FDB heterozygotes in Germany. 5 FDB families and 6 unrelated FDB heterozygotes were genotypes at 4 polymorphic sites in the 3' end of the apo B gene. These sites consisted of the diallelic markers XbaI, MspI, EcoRI and the hypervariable region (3'HVR). In 5 FDB families and 1 unrelated FDB heterozygote the arginine(3500)--- glutamine mutation could be unambiguously assigned to the haplotype XbaI /MspI+/EcoRI-/3'HVR48, in the other 5 FDB unrelated heterozygotes this finding was consistent with the combination of the genotype. The existence of the arginine(3500)----glutamine mutation on the same and supposedly rare allele suggests that the mutant alleles are identical by descent in our population. The fact that the same mutant allele was identified in North America and Austria suggests a common European origin of the arginine(3500)----glutamine mutation. PMID- 1892488 TI - Effects of transforming growth factor-beta 1 on growth of aortic smooth muscle cells. Influences of interaction with growth factors, cell state, cell phenotype, and cell cycle. AB - Transforming growth factor (TGF)-beta 1 may have different effects on cell proliferation depending on many conditions. This paper clarifies the effects of various conditions on the effect of TGF-beta 1 on proliferation of cultured rabbit aortic smooth muscle cells (SMC) and also the time of its action during the cell cycle. TGF-beta 1 at 10-10,000 pg/ml inhibited DNA synthesis of SMC in the G0 stage derived from normal media or atheromatous intima stimulated by either platelet-derived growth factor (PDGF), fibroblast growth factor, SMC derived growth factor, or fetal bovine serum (FBS). TGF-beta 1 also inhibited the growth of SMC in the growing state stimulated by either PDGF or FBS. TGF-beta 1 was effective only when added to the culture within 2 h after stimulation of the G0 state SMC with PDGF. It also inhibited increase in transcription of the c-myc protooncogene on stimulation of SMC with PDGF. These data suggest that TGF-beta 1 inhibited proliferation of SMC irrespective of the cell phenotype, growth conditions, and growth factors present and that it exerted this inhibitory effect during the time of the G0/G1 transition. PMID- 1892489 TI - Effect of lovastatin on the interaction between high density lipoprotein and cultured rat adrenocortical cells. AB - Preincubation of rat adrenocortical cells with lovastatin inhibits high density lipoprotein (HDL3) interaction with rat adrenocortical cells in a dose- and time dependent fashion. Lovastatin causes a decrease in the number of binding sites and a moderate increase in the affinity of HDL binding to cells. Lovastatin also produced a dose- and time-dependent inhibition of cholesterol synthesis in these cells. Dose-dependence, but not time-dependence, of the inhibition of cholesterol synthesis, correlates with that of HDL binding (r = 0.91, P less than 0.004). Incubation of cells with lovastatin for up to 24 h does not change their free or total cholesterol content. The inhibitory effect was apparently not due to a modification of HDL by lovastatin. These results indicate that lovastatin causes a down-regulation of HDL binding sites on cultured rat adrenocortical cells. PMID- 1892490 TI - Estimation of HDL cholesteryl ester kinetic parameters in the cebus monkey, an animal species with high plasma cholesteryl ester transfer activity. AB - We studied the kinetic parameters of high density lipoprotein (HDL) cholesteryl esters in the cebus monkey, an animal species with high plasma cholesteryl ester transfer activity. HDL were radiolabeled with cholesteryl [1-14C]oleate and intravenously administered to 4 cebus monkeys. The calculated fractional catabolic rate (FCR) of the HDL cholesteryl esters was 0.081 +/- 0.002 (mean +/- SD) h-1 and the calculated residence time was 12.3 +/- 0.3 h. The production or disposal rate of plasma HDL cholesteryl esters was 34.3 +/- 4.5 mumol/h. The radiolabeled cholesteryl esters were rapidly transferred from the HDL to the very low and low density lipoproteins (VLDL + LDL) and the amount of tracer in the VLDL + LDL had already reached a maximum at 3.5 +/- 0.7 h after tracer administration. The estimated fraction of VLDL + LDL cholesteryl esters derived from the HDL was 0.77 +/- 0.06. We also used radiolabeled [1,2-3H(N)]cholesteryl palmityl ether to trace HDL cholesteryl esters, but the ether tracer was more slowly cleared from the plasma and less readily transferred between plasma lipoproteins than the ester tracer. PMID- 1892491 TI - Efficacy of cholestyramine does not vary when taken before or during meals. AB - Compliance to cholestyramine treatment, often unsatisfactory, may become further problematic because of the common indication that the resin should not be taken with meals. Since there is no convincing data on the validity of this therapeutic schedule, 10 type IIA hyperlipoproteinemic patients received cholestyramine either before or during the 3 major meals, according to a cross-over protocol. Plasma lipid levels were monitored after 4 and 6 weeks of each treatment schedule. The efficacy of the resin, in terms of total cholesterol (-16.5% together with food vs. -17.2% before food) and of low density lipoprotein cholesterol reduction (-22.8% with food vs. -23.1% before food) did not differ. The side effect profile was also not different between the two treatment protocols. These findings suggest that there are no significant interactions between food and the anion exchange resin and that the hypocholesterolemic effect does not depend upon a specific timing, supposedly close to the gallbladder contraction. They are particularly significant in view of the future availability of new resins in liquid form, suitable for intake during meals. PMID- 1892492 TI - Reverse cholesterol transport: physiology and pharmacology. AB - Reverse cholesterol transport identifies a series of metabolic events resulting in the transport of cholesterol from peripheral tissues to the liver and plays a major role in maintaining cholesterol homeostasis in the body. High density lipoproteins (HDL) are the vehicle of cholesterol in this reverse transport, a function believed to explain the inverse correlation between plasma HDL levels and atherosclerosis. An attempt to stimulate, by the use of drugs, this transport process seems to be of great promise in the prevention and treatment of arterial disease. Only few drugs are now known that can modify the activity of the various factors involved in the process. Clofibrate reduces cholesterol esterification, but the newer fibric acids are generally ineffective as anion-exchange resins. Probucol directly increases the activity and mass of cholesteryl ester transfer protein, thus possibly improving the physiological process of cholesterol removal from tissues. The few available data on the effects of drugs on reverse cholesterol transport should stimulate the search for new agents specifically stimulating this antiatherogenic process. PMID- 1892494 TI - [Dental caries: age, income level and dental care]. AB - We have studied a population of 527 school children between 6 and 17 years old, having as main characteristic to have free odontological care. The prevalence of caries found was 40.4%. The age appears as a risk factor. However, we have not found any influence in the social status. The odontological care is considered essential in the decrease of prevalence of dental caries. PMID- 1892493 TI - Sexually transmitted diseases and condoms: high school students' knowledge, attitudes and behaviours. PMID- 1892495 TI - [Analysis and detection of surface changes and corrosion phenomena in silver cones. Scanning electron microscope and electronic microprobe study]. PMID- 1892496 TI - [The temporomandibular joint in different mammals. A new concept]. AB - The gross anatomy of the temporomandibular joints from omnivorous (pigs), carnivorous (dogs and cats), and herbivorous (cows and sheeps) animals and rodents (rabbits and mice) reveals the existence of right and left temporomandibular joint complex as has been described in humans. Each articular complex includes a temporo-meniscal joint and a mandibulomeniscal joint (in all specimens a combination between a saddle joint and condylar joint). The morphological features of these joints are discussed and the similarities and dissimilitudes between those found in animals and human beings are commented on. PMID- 1892497 TI - [Conceptual review of Behcet's syndrome. Diagnostic and therapeutic criteria]. AB - A review of the literature on clinical, diagnostic and therapeutic aspects on Behcet Syndrom is done. PMID- 1892498 TI - [Attitude of pedodontists toward maxillofacial adenopathies. Apropos of a case of tuberculous adenopathy]. AB - In this present work the authors state the importance of a careful anamnesis in a adenopathy in the maxillofacial pediatric area. Ever though in most cases the origin is purely dental, it can often have another etiology, such as tuberculosis. PMID- 1892499 TI - ["In vitro" study of the bacteriocinogenic capacity of Streptococcus mutans]. AB - In our paper the bacteriocinogen ability of some subspecies of Streptococci mutans has been studied. We have obtained a production percentage of 50%. That production ability was bigger for subspecies mutans than sobrinus in a significative way, who strength the increasing differences between these microorganisms. A brief revision of the role that bacteriocins look like to play in oral ecologist equilibrium and their feasible utilization in dental caries prevention has been done. PMID- 1892500 TI - Structure-activity relationships among methoctramine-related polymethylene tetraamines. 3. Effect of the four nitrogens on M2 muscarinic blocking activity as revealed by symmetrical and unsymmetrical polyamines. AB - Several polymethylene tetraamines related to methoctramine (1) were synthesized and evaluated for their blocking activity on M2 and M3 muscarinic receptors of guinea pig left atria and ileum, respectively. In addition, the role of the number of basic nitrogens on activity was also examined. To this end, a series of polyamines (2-7), incorporating one, two or three fewer nitrogens than methoctramine, were synthesized. Furthermore, diamine diethers (8 and 9) and diamine diamides (10 and 11) were investigated to evaluate the role on affinity of the inner and the outer nitrogens of methoctramine. It was found that the presence of four nitrogens is necessary for optimum activity. The effect of benzylation of inner and outer nitrogens of methoctramine allowed the conclusion that optimum activity is associated with four secondary amine functions. The possible significance of the interaction of the four basic nitrogens of tetraamines with four anionic sites of M2 muscarinic receptors is discussed. PMID- 1892501 TI - New 6-cyano-3-phenyl-1-,2,3,4-tetrahydro-1,2-diazepin-5-ones: synthesis and in vitro antitumor activity evaluation. AB - A series of 6-cyano-3-phenyl-1,2,3,4-tetrahydro-1,2-diazepin-5-ones were synthesized and evaluated in vitro as antitumor agents against several human tumor cell lines. Moderate activity and differential cellular sensitivity were found for a few of the tested compounds. PMID- 1892502 TI - 2H-pyrano[3,2-d]-1-benzoxepin derivatives with platelet antiaggregating and other activities. AB - The synthesis of some N,N-disubstituted 4-amino-5,6-dihydro-3-phenyl-2H pyrano[3,2-d]-1-benzoxepin-2 -ones by reaction of phenylchloroketene with a series of N,N-disubstituted (E)-4-aminomethylene-3,4-dihydro-1-benzoxepin-5(2H) ones, followed by dehydrochlorination of the primary adducts with DBN, is described. Some of these compounds showed a platelet antiaggregating activity in vitro slightly superior to that of acetylsalicylic acid, as well as weak local anesthetic and antiinflammatory activities in mice and rats, respectively. PMID- 1892503 TI - Benzo[6,7]cyclohepta[1,2-b]pyran derivatives with platelet antiaggregating and other activities. AB - The synthesis of some N,N-disubstituted 4-amino-6,7-dihydro-3 phenylbenzo[6,7]cyclohepta[1,2-b]pyran-2(5H) -ones by reaction of phenylchloroketene with a series of N,N-disubstituted 6-aminomethylene-6,7,8,9 tetrahydro-5H-benzocyclohepten-5-ones, followed by dehydrochlorination of the primary adducts with DBN, is described. Some compounds showed a platelet antiaggregating activity in vitro superior or comparable to that of acetylsalicylic acid, as well as a weak local anesthetic activity in mice and antiinflammatory activity in rats. PMID- 1892504 TI - 3,5-Diphenyl-1H-pyrazole derivatives. VIII. N-substituted 3-(4-hydroxy-3,5 diphenyl-1H-pyrazol-1-yl)-propanamides, -propanamines and 2-(4-hydroxy-3,5 diphenyl-1H-pyrazol-1-yl)ethanamines with platelet antiaggregating, hypotensive, antiarrhythmic and other activities. AB - The synthesis of N,N-disubstituted 3-(4-hydroxy-3,5-diphenyl-1H-pyrazol-1-yl) propanamides and -propanamines, starting from 4-benzoyloxy-3,5-diphenyl-1H pyrazole, and of N-substituted 2-(4-hydroxy-3,5-diphenyl-1H-pyrazol-1 yl)ethanamines, starting from 4-acetoxy-1-(2-hydroxyethyl)-3,5-diphenyl-1H pyrazole, is described. Some of the above compounds showed a platelet antiaggregating activity in vitro superior or comparable to that of acetylsalicylic acid, as well as moderate hypotensive, antiarrhythmic, local anesthetic, sedative and antiinflammatory activities in rats and mice. PMID- 1892505 TI - New heterocyclic derivatives of benzimidazole with germicidal activity--IX--HPLC detection of 5-fluoro-2-(5'-nitro-2'-furyl)benzimidazole (F-O-NO2) in biological samples. AB - The HPLC technique for the isolation and quantitation of 5-fluoro-2-(5'-nitro-2' furyl)benzimidazole (F-O-NO2), previously described by the same Authors, in biological samples from mice is reported. Evidence is given that the highest biological concentration and the time needed for reaching it depend both on the dose and on the administration route. In fact, almost the same maximal biological concentration of F-O-NO2 (about 0.18 micrograms/mouse) is reached after 60 min from either 40 mg/Kg IP or 200 mg/Kg os drug administration, whereas the maximal biological concentration of F-O-NO2 (5.75 micrograms/mouse) is reached after 30 min from 120 mg/Kg IP drug administration. PMID- 1892506 TI - A blessing and a curse. Nursing student admissions complicated by oversubscription. AB - Oversubscription of students in a professional nursing program complicates the admission selection process. Recommended improvements include: adopting a point scoring tool for selected criteria, using the college computer database, identifying student special consideration needs, downsizing the admissions committee, and raising the required GPA. PMID- 1892508 TI - Legal issues in the care of patients with anxiety. PMID- 1892509 TI - $$$ of nursing care. Economics for the associate degree nurse. PMID- 1892507 TI - Mentoring magic. PMID- 1892510 TI - When the nurse faces separation and loss. AB - This article discusses the types of separations and losses nurses may experience, factors which affect the reaction to separation and loss. It provides guidelines for the nurse in dealing with separation involving loss in the workplace whether it is personal or is the experience of others. PMID- 1892511 TI - Drug abuse: designer drugs. PMID- 1892512 TI - Nutritional management of intermaxillary fixation patients. AB - Weight loss and infection are two areas of concern when treating intermaxillary fixation patients. When proper and adequate nutritional counseling is performed and reassurance and reinforcement are given by health professionals, the patient's healing, weight maintenance, and general health can be better supported. Individualized nutritional therapy which defines the optimal kilocalories and essential nutrient (carbohydrates, proteins, fats, vitamins, minerals, and water) needs of the patient is necessary for warding off infection, for healing, and for promoting good health. PMID- 1892513 TI - Minorities in American nursing. PMID- 1892514 TI - Real nurses wear white shoes? PMID- 1892515 TI - Anxiety. AB - This CEU learning program defines the concept of anxiety and presents subjective and objective data indicative of feelings of anxiety. Appropriate nursing interventions for varying levels of anxiety are presented. The program also gives two clinical situations in which the patient is experiencing anxiety, and then discusses appropriate specific nursing interventions. PMID- 1892516 TI - Trends in epidemiology of colorectal cancer. PMID- 1892517 TI - Current questions related to an optimal treatment of colorectal liver metastases. PMID- 1892518 TI - Thymopentin and interleukin-2 in combination with 5-fluorouracil and leucovorin in metastatic colorectal adenocarcinoma: preliminary results. AB - Thymic hormones have been shown to exhibit immunorestorative effects in vivo and in vitro, and to enhance the expression of high affinity interleukin-2 (IL-2) receptors on normal human lymphocytes stimulated with phytohemagglutinin. Based on these data, a clinical trial was initiated to determine the effects of the combination of 5-fluorouracil (5-FU) and folinic acid (FA) with thymopentin (TP 5) and interleukin-2 (IL-2) in patients with advanced colorectal carcinoma. Fifteen patients were treated with FA, 200 mg/m2/day by IV bolus, and 5-FU, 400 mg/m2/day as a 30-minute infusion, both given for 5 consecutive days every 28 days. TP-5, 50 mg/day, was administered subcutaneously on days 8-11, and IL-2, 9 million IU/m2 twice daily, was given subcutaneously on days 12-16. Of 8 patients evaluable for response, 4 achieved a response. Two patients had stable disease, and two progressed during treatment. There were no instances of life-threatening toxicity. Two patients developed grade III stomatitis and diarrhea followed by leukopenia and fever, requiring hospitalization. Other toxicities were moderate. These results are only preliminary, and a larger number of patients and longer follow-up are needed to draw meaningful conclusions about the merits of this new approach in cancer treatment. PMID- 1892519 TI - Advanced colorectal cancer: impact of chemotherapy on survival. PMID- 1892520 TI - Sequential methotrexate/5-fluorouracil in advanced colorectal cancer treatment. PMID- 1892521 TI - Combined 5-fluorouracil and recombinant alpha-2a-interferon vs. 5-fluorouracil alone in metastatic colorectal carcinoma: a multicenter randomized study. PMID- 1892522 TI - Preliminary report of high dose folinic acid and 5-fluorouracil alone or combined with hydroxyurea in advanced colorectal cancer: a randomized trial of the Italian Oncology Group for Clinical Research. PMID- 1892523 TI - Therapeutic potential of differentiating agents in colon cancer treatment. PMID- 1892524 TI - Hepatic resections for colorectal metastases: the Italian multicenter experience. AB - In 1989 there were 151,000 new cases of colorectal carcinoma in the United States. Approximately 50% of these patients will be at risk of developing liver metastases together with other sites of recurrence. However, the liver will be the main site of relapse in only 14,000 patients with colorectal cancer. Approximately 25% of patients with colorectal carcinoma have technically resectable hepatic metastases at the time of operation for primary lesion, and an additional 8-25% will develop metachronous hepatic metastases after primary resection. Recent reported experiences with surgical treatment of metastatic colorectal cancer in the liver seem to indicate that hepatic resection has become more acceptable, safe and effective therapy, and offers today when technically possible, the best prospect of survival in a conspicuous number of patients. For these reasons, although a prospective randomized trial has not been done comparing resection with nonresection, resection seems to give the best hope for cure and actually is the treatment of choice for selected patients. In fact in these patients is reported a significant prolongation of survival compared with those patients with unresectable liver metastases treated only with adjuvant therapy in the form of chemotherapy or radiation therapy. Median survival of resected patients with hepatic metastases has been reported to range from 6-12 months, and for patients with single metastases is reported to range from 4.5-6.2 months to 11 and 21 months. The benefits of surgical therapy have been emphasized by different experience, with a 5-year overall survival rate ranging from 20-40%. In a recent multicenter survey a 33% 5-year survival rate was demonstrated in 859 patients resected for hepatic metastases. PMID- 1892525 TI - Local recurrence after curative resection for colorectal cancer: frequency, risk factors and treatment. AB - Analysis of 498 patients with colorectal carcinoma was retrospectively reviewed to evaluate the incidence, risk factors and therapy of local recurrent carcinoma following curative resection. Complete follow-up information was obtained in all but four patients (99.2%). After a median follow up of 42 months, 64 out of 469 (13.6%) patients developed local recurrence (LR). The incidence of LR was higher in rectal than in colon cancer patients (18.3% vs 8.9%) (P less than 0.005). Separate univariate and Cox analyses for rectal patients showed tumor site (P less than 0.02). Dukes stage (P less than 0.002), and adjuvant radiotherapy (P = 0.05) determined risk of LR. For colon cancer patients risk of LR was determined by histological tumor grade (P less than 0.01). Out of 64 patients, 5 (7.8%) underwent radical excision of LR. Forty percent of these survived at 5-year (P less than 0.08). Palliative treatment (radio-chemotherapy) obtained a 5-year survival of 15.3%, with no survivors in no-treatment group. These results suggest that local recurrent colorectal carcinoma remain a difficult treatment problem. More effective combinations of surgery and adjuvant therapy are therefore mandatory to reduce the incidence of local failure in high risk colorectal patients. PMID- 1892526 TI - Clinical evaluation of serum tumor-associated glycoprotein-72 as a novel tumor marker for colorectal cancer patients. AB - A novel tumor marker, tumor-associated glycoprotein-72 (TAG-72), has been identified using monoclonal antibody (MAb) B72.3. Using immunohistochemical techniques, TAG-72 has been found in carcinomas of various origin including colon, stomach, breast, lung, prostate, and ovary, as well as in body fluids. The presence of TAG-72 in serum samples from 260 patients with colorectal disease (malignant or benign) has been evaluated using the CA72-4 assay. Approximately 40% of patients with colorectal cancer exhibit elevated levels of this marker; moreover, the presence of positive levels of TAG-72 significantly correlates with advanced stages of disease, suggesting that TAG-72 may be a good marker of advanced colorectal cancer. Only 2% of the patients diagnosed with colorectal disease had elevated TAG-72 serum levels indicating the high specificity of this marker. A comparative study with carcinoembryonic antigen (CEA) serum levels showed a complementarity of the two tumor markers; in fact, 49.6% of CEA negative cases scored positive for TAG-72. A longitudinal evaluation of TAG-72 serum levels in 31 patients with malignant disease was performed. The results indicate that patients with increasing TAG-72 serum levels postoperatively may be indicative of recurrent disease. In 60% of patients in which significant changes of CEA levels could not be detected, TAG-72 showed rising positive levels prior to clinical evidence of recurrent disease. These results suggest that the simultaneous use of TAG-72 and CEA serum markers may be useful in the diagnosis of recurrent disease and therefore play an important role in the clinical management of cancer patients. PMID- 1892527 TI - Chemotherapy for patients not benefitting from 5-fluorouracil therapy. PMID- 1892528 TI - Clinical staging and pathological correlation in colorectal cancer. PMID- 1892530 TI - Radical surgery for rectal cancer. PMID- 1892529 TI - Radical surgery in rectal cancer patients: what does it mean today? PMID- 1892531 TI - DNA ploidy and cell kinetics in human colorectal carcinomas. PMID- 1892533 TI - Liver surgery for metastases: clinical results. PMID- 1892534 TI - Opinion: resection of hepatic metastasis for colorectal cancer. PMID- 1892532 TI - Hepatic resection: when, what kind, and for which patients. AB - For the patients who develop metastatic colorectal cancer in their liver only, the option of resection of metastatic disease should be considered as a therapeutic modality. The timing of the metastases is not crucial in this decision making process. The size of the metastases is also not a factor, but the number of lesions is important for any off protocol therapy, i.e., there should be four or less lesions. How the lesions are situated is only crucial in the feasibility of resection. Thus bilobar lesions can be just as amenable to cure as unilobar but there has to be a way to leave sufficient liver parenchyma to support survival. The type of resection is also not significantly related to survival. Thus whether a lobectomy, segmentectomy, subsegmentectomy, wedge, or trisegmentectomy is necessary should be entirely up to the operating surgeon. Patients must be aware that they will have a laparotomy with at least a one third chance that a resection will not be done because of extrahepatic disease. For those who do go on to resection the question of the utility of postoperative therapy is unanswered. Promising results with postoperative hepatic artery chemotherapy have not yet been substantiated and await cooperative trial completion. PMID- 1892535 TI - Prognostic factors in colorectal cancer: current status and new trends. AB - The clinical, laboratory, and pathologic data of 361 patients who had curative resections for colorectal cancers were collected and analyzed in a multiple stepwise regression model. In univariate analysis, among clinical factors, bowel obstruction and emergency surgery showed the most significant prognostic value (P = 0.002, P = 0.004, respectively). Vegetating growth, Astler-Coller stage of tumor, intramural spread, lymph node involvement, and synchronous liver metastases resulted in the pathologic variable significantly affecting the prognosis (P = 0.006, P less than 0.001, P = 0.036, P less than 0.001, P less than 0.001, respectively). In the multivariate analysis, stage was the predictive factor with the highest hazard ratio in conjunction with bowel obstruction (P less than 0.0001 in both cases). Processing data excluding stage ("multiparametric factor" itself), hepatic metastases, lymph node involvement, bowel obstruction, and intramural spread appeared as independent predictors of survival (P less than 0.0001, P less than 0.0001, P = 0.0004, P = 0.0316, respectively). Other variables, as biologic and molecular factors, should be more widely tested in order to assess their impact on prognosis. PMID- 1892536 TI - Surgeon's role in diagnostic advances. AB - Surgeons have never intervened in the life of a sick patient merely when technical expertise is required. The unique anatomic, physiologic, and oncologic perspectives the surgeon possesses mandates that he/she play a major role in diagnostic advances and the management of most forms of cancer, especially colorectal cancer. This article briefly outlines the historical posture of surgeons in pursuing diagnostic advances in medicine and particularly colorectal cancer. It also emphasizes that the modern surgical investigator, in collaboration with the basic scientist, should form a critical core of a team of investigators in the pursuit of diagnostic advances. PMID- 1892537 TI - Perioperative radioimmunolocalization of colorectal cancer by radiolabeled monoclonal antibodies. PMID- 1892538 TI - Perspectives in colorectal cancer. AB - This paper presents an overview of recent developments pertaining to colorectal adenocarcinoma. It is aimed toward the practicing clinician. Topics discussed include epidemiologic observations; genetic predispositions; molecular biology findings; screening and early detection programs; endoscopy; principles of surgical resection; laser and radioimmunoguided surgery; staging; selection of patients for adjuvant chemotherapy; and considerations regarding biologic response modifiers and pain control in the advanced-disease setting. PMID- 1892539 TI - Interleukin-1 beta production in vivo and in vitro in rats and mice measured using specific immunoradiometric assays. AB - Activated cells of the monocyte-macrophage lineage produce two forms of the inflammatory cytokine interleukin-1 (IL-1), IL-1 alpha and IL-1 beta, of which IL 1 beta is the predominant secreted form and has a wide range of modulatory effects on the endocrine system. Immunoassays of human IL-1 beta have been described, but are not suitable for measurement of rat and mouse IL-1 beta because of limited cross-reactivity. Polyclonal sheep anti-rat or sheep anti mouse IL-1 beta antisera were used to develop sensitive and specific immunoradiometric assays for rat and mouse IL-1 beta. Secretion of IL-1 beta from endotoxin-activated monocytes or macrophages was measured in vitro or in vivo in both species. In vitro, rat monocytes and mouse macrophages produced IL-1 beta in response to endotoxin, with a relatively small proportion of total IL-1 beta being secreted. In vivo, endotoxin stimulated an increase in plasma IL-1 beta in both animals. The development of these assays will facilitate studies of the role of endogenous IL-1 beta in animal endocrine models. PMID- 1892540 TI - Multiple forms of angiotensin II receptors in rat tissues. AB - Angiotensin II (AII) receptors were identified in rat tissue membranes by specific binding of 125I-labelled AII. Using an isoelectric focusing technique, two forms of the high-affinity AII receptor were identified in rat adrenal zona glomerulosa and liver membranes. These migrated to isoelectric points (pI) 6.8 and 6.7. Two low-affinity forms migrated to pI 6.5 and 6.3. The two high-affinity forms were in greatest abundance in the zona glomerulosa, while the low-affinity pI 6.5 isoform was predominant in liver membranes. In uterine membranes both low affinity isoforms were observed, but there was only one of the high-affinity forms (pI 6.7). Concentrations of AII receptor isoforms were increased in the zona glomerulosa of sodium-deprived rats. Reduction of disulphide bridges with dithiothreitol (DTT) had different effects on the various AII receptor isoforms. Thus 1 mmol DTT/1 caused a twofold increase in 125I-labelled AII binding in zona glomerulosa membranes. DTT produced no appreciable differences in specific AII binding in uterine membranes, whereas there was a 50% reduction of binding in liver membranes. At 20 mmol/l, DTT greatly decreased AII binding in all tissues. The data suggest the existence of multiple forms of AII receptors which may have different functions. PMID- 1892541 TI - 17 Beta-hydroxysteroid dehydrogenases in human breast tissues: purification and characterization of soluble enzymes and the distribution of particulate and soluble forms in adipose, non-adipose and tumour tissues. AB - 17 Beta-Hydroxysteroid dehydrogenase (17 beta-HSD) is present in multiple forms in human breast tissue. One soluble form, with a molecular weight of approximately 35 kDa, was purified to near homogeneity from whole normal breast tissue. This form catalysed the oxidation of oestradiol and the reduction of oestrone, with NADP+ and NADPH as the preferred coenzymes. Three other soluble forms with higher molecular weights (in the range 50-80 kDa) were isolated. They catalysed the oxidation of oestradiol but not the reduction of oestrone, and all of them had properties very different from those of the low molecular weight enzyme. Activities of 17 beta-HSD were measured in particulate and soluble fractions from normal breast adipose and non-adipose tissues, and from breast tumours obtained from post-menopausal women, in the oxidative direction with NAD+ and NADP+ as coenzymes and in the reductive direction with NADH and NADPH as coenzymes. Particulate fractions from tumours had much higher oxidative and reductive activities than those from normal tissues. Soluble fractions from tumours had higher oxidative activities than those from the normal tissues but similar reductive activities. The major soluble form of 17 beta-HSD in adipose tissue was the 35 kDa enzyme which had both oxidative and reductive activities. In contrast, the majority of the soluble activity in non-adipose tissue was due to enzymes, with molecular weights in the range 50-80 kDa, which had oxidative activity only. The soluble fractions of tumours, like those of non-adipose tissue, contained enzymes with molecular weights in the range 50-80 kDa. In addition, they contained a 35 kDa enzyme with properties different from those of the enzyme with the same molecular weight present in adipose tissue. PMID- 1892542 TI - Lack of expression of the mRNA encoding a major protein of the mouse vas deferens after neonatal exposure to oestrogens. AB - We have previously characterized an androgen-inducible secretory protein from the mouse vas deferens (MVDP), and a cDNA to its mRNA has been obtained. This report describes altered MVDP gene expression after neonatal exposure to oestrogens. As shown by immunohistochemistry and Western blot analysis, MVDP was missing in the vas deferens from adult mice neonatally exposed to oestrogens. Northern blot analysis showed that the expression of MVDP mRNA was also suppressed. Exogenous testosterone was unable to stimulate MVDP production (either message or protein) in neonatally oestrogenized males. The results suggest that the alterations in gene expression in the oestrogen-exposed vas deferens reflect changes in the programme of differentiation of the organ itself. PMID- 1892543 TI - Involvement of calmodulin in depolarization-induced release of corticotrophin releasing hormone-41 from the rat hypothalamus in vitro. AB - We have employed an acute explant system of the rat hypothalamus in vitro, as previously described, to examine the role of calcium and calmodulin in the release of corticotrophin-releasing hormone-41 (CRH-41). Release of CRH-41, as determined by radioimmunoassay, was stimulated in a dose-dependent manner by the membrane-depolarizing agents KCl and veratridine. Stimulation was also observed with the calcium ionophore A23187. The calcium channel blocker verapamil (1-100 mumol/l) inhibited both KCl- and veratridine-induced release in a dose-dependent manner (maximum inhibition of 75% and 60% respectively), thus providing further evidence that calcium entry is required for secretion of CRH-41 following membrane depolarization. Trifluoperazine (1-100 mumol/l), an inhibitor of calmodulin-calcium interaction, decreased both KCl- and veratridine-evoked CRH-41 secretion in a dose-dependent fashion (maximum inhibition of 50% and 30% respectively). Similarly, phenytoin, a calmodulin-dependent kinase inhibitor, in the concentration range of 1-100 mumol/l, also decreased depolarization-induced CRH-41 release in a dose-dependent manner. The basal release of CRH-41 was unaffected by either treatment. Finally, both calmodulin inhibitors (10 mumol/l) decreased CRH-41 release induced by the calcium ionophore A23187 (10 mumol/l). These data provide evidence for the role of calcium in membrane depolarization induced stimulus-secretion coupling of rat hypothalamic CRH-41. Furthermore, inhibition of the stimulatory responses by two separate classes of calmodulin inhibitors suggests a role for calmodulin, at least in part, in this process. PMID- 1892544 TI - Regulation of the type-II gonadotrophin alpha and beta subunit mRNAs by oestradiol and testosterone in the European eel. AB - The gonadotrophic function of the European eel (Anguilla anguilla L.) at the silver stage is very weak: gonadotrophin-releasing hormone (GnRH) secretion is deficient and, moreover, dopamine inhibition overrides GnRH action. At the silver stage, oestradiol stimulates the biosynthesis of the type-II gonadotrophin (GTH II). To study the molecular mechanism of this activation further, we examined the effect of testosterone and oestradiol administration on pituitary levels of mRNA encoding GTH-II alpha and beta subunits. Corresponding eel cDNA probes and Northern blot analysis were used. After 2 weeks, testosterone and oestradiol implantation resulted in a strong increase in mRNA encoding the GTH-II beta subunit (7-fold and 25-fold, respectively) and in a slight, but non-significant, rise in the a subunit mRNA level (1.8-fold and 1.5-fold, respectively). Co implantation of these two steroids suggested a potentiation of their effects on the beta subunit (104-fold) while an additive effect was indicated on the alpha mRNA level (2.9-fold). Effects were detectable within 4 days and were maximal 4 weeks after implantation. These results indicate that in the European eel at the silver stage, gonadal steroids stimulate differentially the expression of GTH-II subunit genes at a pretranslational level. PMID- 1892545 TI - Studies on the activation of the oestrogen receptor bound to the anti-oestrogens 4-hydroxytamoxifen and ICI 164,384 by using three monoclonal antibodies. AB - Three monoclonal antibodies, H222, H226 and D547, which provided evidence of the structural transformation and change in exposure of the functional domains of the oestrogen receptor from fetal guinea-pig uterus upon activation, were used to study the receptor bound to the anti-oestrogens 4-hydroxytamoxifen and ICI 164,384. No differences in the structure of non-activated 4-hydroxytamoxifen- and ICI 164,384-receptor complexes, as compared with the oestradiol-receptor complex, were detected by the three monoclonal antibodies. When heated at 28 degrees C, both anti-oestrogen-receptor complexes became capable of binding the D547 antibody, which reacts selectively with the activated receptor; however, this binding was lower than that of the oestradiol-receptor complex. The interaction with the H226 antibody showed that anti-oestrogens can induce receptor dimerization, but to a lesser extent than oestradiol. In addition, both anti oestrogen-receptor complexes can bind to DNA-cellulose and are retained in nuclei from intact cells at 28 degrees C, but less efficiently than the oestradiol receptor complex. On the other hand, the nuclear receptor seems to have a similar dimeric structure when bound to either anti-oestrogens or oestradiol, as detected by the three monoclonal antibodies. The data suggest that 4-hydroxytamoxifen and ICI 164,384 induce and impaired activation of the oestrogen receptor; this difference, although quantitative rather than qualitative, might be related to the partial agonistic action of these anti-oestrogens in the fetal guinea-pig uterus. PMID- 1892546 TI - Use of human keratinocytes cultured on fibrin glue in the treatment of burn wounds. AB - Keratinocytes isolated from a small skin biopsy and cultured according to the method of Rheinwald and Green (Cell 1975, 6: 331) are able to undergo rapid expansion in vitro and have been used successfully in the treatment of burn wounds. One of the inconveniences of this method involves the transfer of the epidermal sheet from the culture flask onto the wound bed. One way to facilitate this process is to use fibrin glue (Biocol) as a culture bed for the keratinocytes. Burns are then grafted by simply placing the sheet of fibrin glue and keratinocytes onto the wound bed. This process has been successful in two patients, permanently covering areas of 720 cm2 and 5342 cm2. The newly formed epidermis was fully differentiated and histologically normal after 1 year. The efficiency of this improved, faster procedure could lead to a new approach in the treatment of extensive burn wounds. PMID- 1892547 TI - Plasma fibronectin levels as predictive of survival in major thermal injury. AB - Plasma fibronectin levels, assayed by rocket immunoelectrophoresis, were measured in adult burn patients with 25-75 per cent total body surface area burns. Significant differences in the level of plasma fibronectin were detected in the one fatally injured patient prior to death (at 48 and 24 h) as a precipitous and persistent drop to 0.07 and 0.09 g/l, respectively. This deficiency coincided with early clinical signs of sepsis, the severity of which was not clinically apparent prior to overwhelming sepsis and incipient shock. This report supports previous suggestions that secondary deficiencies in plasma fibronectin may be predictive of mortality occurring after day 6 postburn. The need for routine assay of plasma fibronectin using rocket immunoelectrophoresis is demonstrated. PMID- 1892548 TI - Specific changes in peripheral blood lymphocyte phenotype from burn patients. Probable origin of the thermal injury-related lymphocytopenia. AB - T-lymphocyte subsets from 27 severely burned patients and 32 controls were analysed using monoclonal antibody immunofluorescent staining and flow cytometry. Compared to normal controls, burn patients showed a remarkable reduction in absolute number of CD3-lymphocytes in the 48 h following injury, which was accounted for by a decrease in both CD4 and CD8 subsets. Activated lymphocytes, as defined by expression of CD25, CD69 and CD71, were significantly increased in burned patients. Additionally, a moderate increase in lymphocytes bearing simultaneously CD4 and CD8 was observed in some burned patients. The expression of CD11c, CD49a and CD54, members of the integrin family of cell surface molecules, was shown to be increased on lymphocytes from thermally injured patients. We conclude that thermal injury produces a profound T-cell lymphopenia with features of extensive T-cell activation, and postulate that depletion of circulating T-cells could be related with the expression of surface adhesion molecules and cell redistribution from blood to the tissues. PMID- 1892549 TI - Effect of platelet activating factor on reticuloendothelial system function. AB - The effect of platelet activating factor (PAF) injections on the uptake of 99mTc SC (99mTc-SC (99mTc-sulphur colloid) was determined in vivo. PAF (2 micrograms) injected intravenously into unanaesthetized, unrestrained rats was associated with the development of lesions in the small intestine and alteration of 99mTc-SC uptake in vivo. 99mTc-SC uptake into the lung was increased while spleen uptake was decreased. Pretreatment of the animals with a PAF antagonist, SRI-64-441, prevented the intestinal lesions and alterations of 99mTc-SC uptake. Macrophages, isolated from lung lavage of the PAF-treated rats, demonstrated a decreased generation of hydrogen peroxide in vitro. The present results suggest that, in addition to its other effects on the immune system, PAF can also alter the in vivo phagocytic activity of the reticuloendothelial system in the rat. PMID- 1892550 TI - The phosphorous burn--a preliminary comparative experimental study of various forms of treatment. AB - White phosphorous burns were inflicted on 44 Wistar (CR) rats. All animals of the control (C1) group (untreated white phosphorous burns) died within 48 h while those of the control (C2) group (wound only, no white phosphorous burns) survived at least 6 days. Copper sulphate, either as a solution or as an emulsion, proved lethal even without white phosphorous burns. Water irrigation alone proved to be a life-saving procedure for the white phosphorous burned rats. PMID- 1892551 TI - An analysis of burn mortality: a report from a Spanish regional burn centre. AB - This paper reports an analysis of the mortality rates and related factors in our Burn Centre, based on 710 patients treated between 1985 and 1988. The average age of the patients was 23.8 years and the average burn size was 14 per cent of the body surface area. Burning injury affected mainly men (66 per cent), and their mortality rate was higher than that of women. The overall mortality rate was 6.6 per cent, the average age of the fatally injured patients being 54 years. We confirm that mortality in burned patients is closely related to: age (51 per cent of the patients were over 60 years of age); burn size (68 per cent of the patients had burns covering more than 30 per cent TBS); burn depth (57.4 per cent had full skin thickness burns); inhalation injury (present in 66 per cent of the fatally injured); and associated risk factors. The main cause of the burning injury was flames, chiefly from domestic accidents. The average survival time for the fatally injured patients was 10 days. Finally, our expected mortality followed a linear regression model, the LA50 for patients with only full skin thickness burns was 50 per cent. PMID- 1892552 TI - Utilization of human cultured epidermal keratinocytes: irreversibility of the inhibition of proliferation induced in stored detached cultures. AB - In order to look for the best conditions required for the utilization of cultured epithelium in the treatment of burn wounds, some experiments have been performed studying the storage of dispase-detached cultures. The viability of keratinocytes and, after trypsin dissociation of the cultures, the adhesion and proliferative potential of living keratinocytes were measured. Our laboratory investigations suggest that the storage period of detached cultures has to be kept as short as possible to preserve the keratinocytes' growth potential. PMID- 1892553 TI - Thermal damage to skin collagen. AB - The effect of temperature upon the solubility of frozen skin collagen in vitro and its susceptibility to digestion by proteolytic enzymes has been studied. Both of these parameters are increased with temperature. Above 52 degrees C there is a sudden increase in both the solubility of collagen and its susceptibility to digestion, suggesting that this temperature is associated with changes in the structure of the skin collagen. This increase in susceptibility to digestion may have an influence upon the nature of the healing process in the burn wound. PMID- 1892554 TI - Aetiology of burn injuries among children aged 0-4 years: results of a case control study. AB - During the year 1987/1988 a case-control study was conducted, by means of a postal questionnaire, among parents of children aged 0-4 years. Cases (n = 122) were 0-4-year-old Dutch children who visited emergency departments with burn injuries. Controls (n = 213) were a sample of the Dutch population of 0-4-year old children without burn injuries. Odds ratios based on logistic regression (OR LR) and 90 per cent confidence intervals (CI (90 per cent) were calculated for a number of putative risk factors. The risk of burns was higher for children with other than Dutch (e.g. Turkish) ethnicity (OR-LR = 5.6; CI (90 per cent) = 2.6 11.9). Children who lived in relatively small houses turned out to have a higher risk of burns (OR-LR = 2.5; CI(90 per cent) = 1.3-4.7). To our surprise, children belonging to lower socioeconomic classes were found to have a decreased risk of burns (OR-LR = 0.3; CI (90 per cent) = 0.1-0.6). Furthermore, among several manipulatable risk factors, the use of an oven window which gets hot while in use appeared to have an increased risk of burns (OR-LR = 2.1; CI(90 per cent) 1.3 3.5). The same holds for the storage of hot drinks in their original pots instead of in vacuum flasks (OR-LR = 2.0; CI (90 per cent) 1.2-3.1). Cooking on a gas stove was found to be another risk factor (OR-LR = 2.5; CI(90 per cent) 1.1 10.0). PMID- 1892555 TI - Management of hypertrophic scars on the pubic area with an iliac flap. AB - Postburn hypertrophic scars on the pubic area are rare. A local iliac flap has been used in four female patients for covering the raw areas after total excision of these scars. The largest flap in this series was 7 x 13 cm. Although bilateral flaps could be used simultaneously, only a unilateral flap was used in each patient. All the donor sites were closed primarily. The postoperative course was uneventful in each patient. Itching subsided completely in all patients and distortions of the genitalia were corrected. There was no recurrence of the scar formation in the follow-up period from 2 to 7 years. The only drawback of this flap for coverage of the symphysis pubis is that it is hairless. The experience with the present patients proved that this is an easy, quick and reliable method for removing hypertrophic scars on the pubic area. PMID- 1892556 TI - A thrombin ointment that achieves rapid haemostasis of split thickness donor wounds, particularly on the scalp. AB - A procedure is described to achieve rapid haemostasis of split thickness donor wounds by using an ointment containing thrombin (10,000 units mixed in 10 g of petroleum jelly-based gentamicin ointment). The ointment, prepared just before the removal of the skin graft, is immediately spread over the wound after the graft has been taken. With this technique, a steady haemostasis is promptly and simply achieved without the recurrence of bleeding compared to the technique using only a thrombin solution (bleeding time: a mean of 11.5 s for the thrombin ointment and 25.5 s for the thrombin solution, P less than 0.01). Thus, particularly when many skin grafts are needed, further skin grafts from adjacent areas can be readily taken without interference by bleeding. This procedure has proved to be extremely useful in achieving rapid haemostasis of split thickness skin donor wounds, especially when taking skin grafts from the scalp. PMID- 1892557 TI - Burn care facilities in Israel. PMID- 1892558 TI - Duoderm application on scalp donor sites in children. AB - In a search for an invisible skin donor site and a comfortable dressing for the donor site, a study was designed in which the scalp was used as the donor site and Duoderm was applied as the dressing. The study contained 18 children with minor burns. A Duoderm dressing on scalp donor sites showed a normal healing time. In using the scalp as a donor site the patient can be mobilized very quickly after the operation and the scar is hidden and invisible 1 month postoperation. PMID- 1892560 TI - Cellophane--a dressing for split-thickness skin graft donor sites. AB - Cellophane paper has been used as a dressing for split-thickness skin graft donor sites in 251 patients between October 1985 and December 1989. Twelve donor sites in 10 patients were observed in detail to assess the usefulness of this material. The results of the study are presented and the merits and disadvantages of this dressing material have been discussed. In the opinion of the authors the cellophane paper dressing was found to be most satisfactory. It is also cheaper than the newly available dressing materials for the skin donor area. PMID- 1892559 TI - Immediate dressing of the burn wound--will it change its natural history? AB - Thirty deep dermal burns were inflicted on six domestic pigs. On the treated animals, the epidermis was removed and immediately replaced with Omiderm, Xeroform or Mettalin dressings. Burns in which the blister was left intact or not dressed after epidermis removal, served as controls. Macroscopic and microscopic assessment of the healing process was then carried out. Surprisingly, the no epidermis controls healed somewhat faster than did the untreated controls (those with blister intact). On day 7, 83 per cent of the treated lesions showed initiation of epidermal regeneration, compared with 58 per cent in the no treatment and no-epidermis controls. All dressing materials were found equal in this model, and differences between control and treatment groups were not significant after 12 days. PMID- 1892561 TI - Ability of microautotransplants to re-epithelialize deep and extensive skin injuries. AB - Experiments with rats of different ages have established the potential of microautotransplants (MATR) of skin (0.5-3.0 mm2 in size) to produce neoepidermis on fresh and granulating wounds. The MATR induced a 40-fold increased rate of closing of the wound surface. Contraction of the re-epithelialized wounds followed the same trend found for an open wound. The rate of contraction of re epithelialized wounds depends on the age of the rat and the degree of maturity of the granulation tissue. The most extensive contraction was observed in young animals. Neoskin does not contain skin appendages, shows increased exfoliation of horn flakes from the neoepidermis surface and contains epitheloid cysts filled by a horny substance. The use of the MATR technique in the clinic also leads to wound re-epithelialization. Human neoskin histologically is similar to that of animals. These results suggest that the MATR technique is an alternative approach in the treatment of extensive skin burns. PMID- 1892562 TI - The role of bone scans in electric burns. AB - From June 1986 to May 1989, 17 patients who sustained high tension electric burns received preoperative 99mTc-MDP bone scan examinations. They were done to detect soft tissue and bone injury and also as a guide for debridement and amputation. From our experience, the correlation between the results of scanning and clinical findings is 88.9 per cent. They are very sensitive and reliable for decision making regarding debridement and limb amputation level when there is coagulation necrosis. PMID- 1892563 TI - Purulent pericarditis in an adult burn patient treated with survival. AB - A 41-year-old white-skinned male admitted with 40 per cent total body surface area partial and full skin thickness burns developed septic pericarditis. He had a severe inhalation injury and subsequent pneumothorax. Multiple fibreoptic bronchoscopies were required. The septic pericarditis required pericardectomy which was carried out in two stages. The extensive burns required multiple operations. The patient eventually made a complete recovery. PMID- 1892564 TI - Construction of three-dimensional stick figures from branched DNA. AB - Stable DNA branched junction molecules can be used as the building blocks for stick-figures in which the edges are double-helical DNA and the vertices correspond to the branch points of the junctions. Sticky-ended cohesion is used to direct the association of individual branched complexes. The sequences of these molecules are assigned by a sequence-symmetry minimization procedure. Successful ligation experiments include the oligomerization of individual three arm and four-arm junctions, the assembly of a quadrilateral from four junctions with different sticky ends, and the recent construction of a molecule with the connectivity of a cube. Possible applications include the assembly of molecular electronic devices, the formation of macromolecular-scale zeolites to host biological complexes for diffraction analysis, and the development of new catalysts. PMID- 1892565 TI - Transclival surgery. PMID- 1892566 TI - Penetrating craniocerebral injuries in civilians. AB - During a 6-year period (1984-89), 31 patients were treated at Rambam Medical Center with penetrating craniocerebral injuries (PCCI) not associated with military action. Eighteen (58%) patients died during their initial hospitalization; only two of them had admission Glasgow Coma Scale (GCS) above five. The admission GCS coupled with the mode of injury (type of missile and motivation of shooting) were valuable for early accurate prognosis assessment. Patients with admission GCS of 3 and 4 invariably died despite rapid treatment and attempted haematoma evacuation. The neurological status, CT appearance, as well as the motivation of shooting should be considered in order to assess accurately the possible outcome. Compared with our military series of 113 patients with PCCI, there were more extensive injuries, although the mean period until neurosurgical treatment was the same. Long-term complications connected to dural tears remote from the entrance wound occurred in three of the survivors. PMID- 1892567 TI - The treatment of spondylotic cervical myelopathy by multiple subtotal vertebrectomy and fusion. AB - The authors report their experience in the treatment of cervical spondylotic myelopathy by multiple subtotal vertebrectomy and fusion. There were 27 cases with a mean age of 66.9 years. The clinical assessment was carried out using both the Nurick and the Japanese Orthopaedic Association (JOA) grading pre- and post operatively at 6 months. The post-operative radiological assessment was done at 3 and 6 months. Two cases died from unrelated medical problems. There were three cases of graft dislodgement. Clinical improvement was detected in 80% of cases using the Nurick grading and in 88% of cases using the JOA scoring. No cases deteriorated neurologically after operation. Bony fusion was achieved in 96% of the surviving cases by 6 months. Multiple subtotal vertebrectomy and fusion is therefore an effective method for the treatment of cervical spondylotic myelopathy. PMID- 1892568 TI - Neurosurgical experience with carotid endarterectomy: a 12-year study. AB - In the 13-year period from 1975 to 1988, 91 carotid endarterectomies were performed on 83 patients in a neurosurgical unit. Sixty-seven of these patients had continued to have symptoms after the best medical treatment. Seventy-one presented with transient ischaemic attacks (TIAs), nine with TIA and minor completed stroke (MCS), and three with MCS alone. Follow-up ranged from 8 months to 12 years with a mean of 5.5 years. Within the follow-up period, including operative complications, four deaths of cerebral origin (4.8%) and three major cerebral events (3.6%) occurred--an annual stroke morbidity and mortality rate of less than 1.5%, which compares favourably with a minimum stroke risk of 5% per annum for the first 3 years following a TIA and 3% for subsequent years. The annual stroke and/or vascular death rate including myocardial infarction was 3.5% compared to an expected stroke and/or vascular death rate of 7.4%. It appears that carotid endarterectomy is a useful adjunct to medical therapy. Myocardial ischaemia is the major cause of death in the follow-up period in this group of patients. It is suggested that patients with TIAs and MCS should be investigated, and those who do not respond to medical therapy should be identified for carotid endarterectomy. PMID- 1892569 TI - Brain stem glioma: the role of a biopsy. AB - A retrospective review of the clinical and histopathological features of 31 patients with brain stem gliomas treated between 1965 and 1990 at Kyushu University Hospital was performed to determine the role of biopsy on these lesions. These 16 male and 15 female patients ranged in age from 3 to 50 years at diagnosis (average: 18.1 years). The primary site of the tumour was the pons in 20 patients, followed by the medulla oblongata and midbrain, and the final histological diagnoses of the lesions based on either the biopsy or autopsy materials were grade I astrocytomas in five patients, grade II in nine, grade III in 10, grade IV in five, and ependymoma in two patients. No consistent correlation could be obtained between the CT findings and histological diagnoses. Open surgical posterior fossa exploration was performed on 17 patients (diagnostic biopsy: 10; volume reduction by tumour removal with or without cyst evacuation: 7) and stereotaxic biopsy on three patients, without any mortality related to these procedures. In our biopsy series, half of the patients with grade II astrocytoma died within 12 months after diagnosis, whereas three out of four patients with grade I astrocytoma survived more than 10 years after diagnosis. Because of the relative safety of the tissue sampling technique, and the importance of an accurate diagnosis in order to select appropriate treatment modalities, histological verification of the lesion should be considered for all patients harbouring a brain stem mass lesion. PMID- 1892570 TI - Non-traumatic CSF fistulae: clinical history and management. AB - Non-traumatic 'spontaneous' CSF fistulae are uncommon. The clinical features of 23 patients treated for non-traumatic CSF fistulae are presented. Twenty of these patients had normal CSF pressure and six developed meningitis. Surgical repair of these fistulae is recommended in order to reduce the risk of meningitis. For this their localization is essential. PMID- 1892571 TI - Investigation and treatment of a multiple limb birth. AB - We report a baby born with three fully developed normally functioning legs. The third leg was attached to the baby's sacrum via an iliac bone at the site of a spina bifida. A primitive perineum was present. Innervation of the limb was via a sacral hiatus with a myelomeningocele. A rudimentary peritoneal sac was found at operation containing a blind loop of bowel suspended by a mesentery. The additional leg was found to have no cortical representation using somatic evoked potentials although lumbar responses were normal. Magnetic resonance imaging demonstrated a bifid spinal cord in the lumbo-sacral region. Associated abnormalities were a haemangioma of the L orbit and a vascular mass in the cerebellum. PMID- 1892572 TI - Cell proliferation in serial biopsies through human malignant brain tumours: measurement using Ki67 antibody labelling. AB - Cell proliferation was assessed in brain tumours using the monoclonal antibody Ki67 which recognizes a nuclear antigen expressed by proliferating cells. Using a novel stereotactic biopsy procedure, serial 1 cm biopsies were taken along a trajectory through six malignant brain tumours. Specimens were also obtained from 10 other brain tumours during conventional surgery. The percentage of Ki67 positive cells was determined as a fraction of the total number of tumour cells present. The Ki67 index for anaplastic astrocytomas and glioblastomas was significantly higher (Ki67 index range 11-18%) than that for benign or low grade tumours. Significant variation in proliferation was measured along the biopsy track through individual tumours (e.g. 0-12.3%) which correlated well with histological appearance. The Ki67 indices of normal brain were very low. In general the Ki67 indices increased with increasing histological grade and also appear to be a useful indicator of the active tumour volume and margin. This method provides spatial information about tumour proliferation which may be used to decide between different treatments and relate to prognosis. PMID- 1892573 TI - The role of the perforated segment of the ventricular catheter in cerebrospinal fluid leakage into the brain. AB - Two cases of gross post-operative cerebrospinal fluid (CSF) leakage along an indwelling ventricular catheter are reported. The CSF appeared to leak through the perforations of the ventricular catheter, as well as at the site of penetration of the ventricular wall. A small or slit ventricle with high intraventricular pressure may thus be a predisposing factor for this localized CSF collection. PMID- 1892574 TI - Intracranial squamous cell carcinoma arising in remnant of extirpated epidermoid cyst. AB - Development of a squamous cell carcinoma in an epidermoid cyst is rare. A case is presented in which such malignant change arose in the capsule remnants of an intracranial epidermoid removed 31 years previously. The limited literature dealing with this late sequela is summarized. PMID- 1892575 TI - Cerebello-pontine angle paraganglioma simulating an acoustic neurinoma. AB - An unusual case of paraganglioma arising from the internal auditory meatus and growing into the cerebello-pontine angle is reported. Clinical features, pre operative radiological appearances and intra-operative findings were indistinguishable from those of an acoustic neurinoma. However, the paraganglionic nature of the tumour was confirmed by the electron microscopic evidence of neurosecretory features. PMID- 1892576 TI - Cervical arterial dissection following trauma. PMID- 1892578 TI - Modification of pre-CT Leksell stereotactic frames. PMID- 1892579 TI - Seventh conversation in biomolecular sterodynamics. June 18-22, 1991. PMID- 1892577 TI - Cerebrospinal fluid rhinorrhoea associated with colloid cyst. AB - Three cases of non-traumatic cerebrospinal fluid (CSF) rhinorrhoea secondary to colloid cysts are presented. Non-traumatic CSF rhinorrhoea is rare and in only two previous reports has it been attributed to a colloid cyst. PMID- 1892581 TI - Comparison of different approaches for calculation of polyelectrolyte free energy. AB - We consider the problem of the mean field (Poisson-Boltzmann) calculation of the electrostatic free energy for a strongly charged polyelectrolyte such as DNA in a salt solution. We compare two approaches to calculate the free energy: (i) direct one starting from the statistical-mechanical expression for the electrostatic free energy and (ii) the polyion charge variation method. In the infinite dilution limit (in respect to polyion) and in excess salt (IDLES) the two approaches are fully equivalent. This is shown by straight forward algebra. We have performed specific calculations of the free energy difference for the case of B-Z transition in DNA as a function of ionic strength. As expected, the two approaches led to identical results. The ionic strength dependence of the B-to-Z free energy proves to be concaved up and as a result Z-DNA is stabilized at low ionic concentration as well as at high salt, in full agreement with our previous results (M.D.Frank-Kamenetskii et al., J. Biomol. Struct. Dyn. 3, 35-42 (1985]. Our data quantitatively agree with the results of Soumpasis (D.M.Soumpasis, J. Biomol. Struct. Dyn. 6, 563-574 (1988]. However, his claim about the absence of the effect of stabilization of Z-DNA at low salt proves to be groundless, and the criticism of our earlier approach seems to be irrelevant. PMID- 1892580 TI - Decisions in force field development: an alternative to those described by Roterman et al. (J. Biomol. Struct. Dyn. 7, 421 (1989)). AB - We attempt to give an alternate point of view of the analysis by Roterman et al. (J. Biolmol. Struct. Dyn. 7,415 (1989]. In particular, we argue for the use of flexible geometry and explicit inclusion of solvent effects in analyzing phi, psi maps of peptides. PMID- 1892582 TI - Parallel double stranded helices and the tertiary structure of nucleic acids. AB - Thermal denaturation of four oligonucleotides, viz. 3'-d(AT)5pO(CH2)6Opd(AT)5 3'(par(AT], 3'-d(AT)5pO(CH2)6Opd(AT)5-5'(anti(AT],3'-d(A)10pO(CH2) 6Op(T)10 3'(par(A-T], and 3'-d(A)10pO(CH2)6Opd(T)10-5' (anti(A-T], was studied in 0.01 M phosphate buffer, pH 7, in the presence of 0.1, 0.25, 0.5 and 1.0 M NaCl. All the oligomers were found to exist at a lower temperature (0 to 20 degrees C) as complexes composed either of two oligomer molecules (a canonical duplex) or of more oligomer molecules whereas, at a higher temperature (30 to 70 degrees C), they formed hairpins with a parallel (par(AT) and par(A-T] or antiparallel (anti(AT) and anti(A-T) orientation of the chains. Melting curves (A260(T] were used to calculate thermodynamic parameters for the formation of hairpins and "low temperature" duplexes. Experiments on ethidium bromide binding to the oligonucleotides have shown that the oligomer anti(A-T) exists, at a low ionic strength, as a four stranded complex ("quadruplex") contains two antiparallel helices, d(A).d(T), which have a parallel orientation and are bound to one another owing to the formation of additional hydrogen bonds between nucleic acid bases. The possible biological function of quadruplexes is discussed. PMID- 1892583 TI - Salt dependent changes in structure and dynamics of circular single stranded DNA of filamentous phages of Escherichia coli. AB - We have analyzed the static and dynamic behaviour of the circular single stranded DNA of the filamentous Escherichia coli phages F1 and M13mp8 in solution as a function of salt concentration using static and dynamic light scattering and sedimentation analysis in the analytical ultracentrifuge. We show by static light scattering that native and denatured single stranded DNA behave like a randomly coiled macromolecule at all salt concentrations used. The size of the native single stranded DNA is governed by the formation of secondary structures. While the radius of gyration decreases with increasing salt concentration the translational diffusion of the center-of-mass of native single stranded DNA and the sedimentation coefficient increase with increasing salt concentration in a biphasic manner. Below 100 mM monovalent cation concentration there is a strong dependence of the hydrodynamic parameters upon salt which is reduced approx. 3 fold at higher salt concentrations. We attribute the compaction of single stranded DNA by salt to electrostatic shielding and, in case of native single stranded DNA, secondary structure formation. Internal motions of the native single stranded DNA are observable at all salt concentrations and can be interpreted with a model of segmental diffusion of the elements of the polymer chain. The observed segmental diffusion coefficient of the native single stranded polynucleotide increases with increasing salt under the conditions investigated. PMID- 1892584 TI - Structure and dynamics of the complex of single stranded DNA binding protein of Escherichia coli with circular single stranded DNA of filamentous phages. AB - We have analyzed the equilibrium and nonequilibrium properties of the complex of the single stranded DNA binding protein of Escherichia coli (EcoSSB) and circular single stranded DNA of filamentous phages M13mp8 and F1 using static and dynamic light scattering, analytical ultracentrifugation and electron microscopy. Upon binding to the single stranded DNA the EcoSSB tetramer replaces an equivalent volume of water trapped within the coiled single stranded DNA and hinders the folding of the single stranded DNA into secondary structures at all salt concentrations. The salt dependent compaction of the stoichiometric complex can be described assuming a flexible polyelectrolyte chain. The solution structure of the macromolecular complex is a random coil and in the electron microscope a beaded flexible structure of the complex with a bead diameter of 6 nm appears at all salt concentrations used. The internal motions of the stoichiometric complex can be described by the Rouse-Zimm model of polymer dynamics. The segmental mobility of the complex can be correlated with changes in the binding site size of the EcoSSB tetramer; it indicates the presence of interactions between EcoSSB tetramers bound to single stranded DNA. PMID- 1892585 TI - The structure and dynamics of H1-depleted chromatin. AB - The size of DNA involved in the interaction with a histone octamer in H1-depleted chromatin was re-examined. We compared the thermal untwisting of chromatin DNA and naked DNA using CD and electrophoretic topoisomer analysis, and found that DNA of 175 +/- 10 base pairs (bp) in length interacted with the histone core under physiological conditions. The decrease of ionic strength below 20 mM NaCl reduced this length down to 145 bp: apparently, an extra 30 bp DNA dissociated from the histone core to yield well-known 145-bp core particle. Histone cores partly dissociate within the temperature range of 25 to 40 degrees C. Quantitative analysis of histone thermal dissociation from DNA shows that the size of DNA protected against thermal untwisting would be significantly overestimated if this effect is neglected. The results presented in this paper also suggest that the dimers (H2A, H2B) act as a lock, which prevents transmission of conformational alterations from a linker to nucleosome core DNA. The histone core dissociation as well as (H2A, H2B) dimer displacement are discussed in the light of their possible participation in the eukaryotic genome activation. PMID- 1892586 TI - A new approach to the rapid determination of protein side chain conformations. AB - Two efficient algorithms have been developed which allow amino acid side chain conformations to be optimized rapidly for a given peptide backbone conformation. Both these approaches are based on the assumption that each side chain can be represented by a small number of rotameric states. These states have been obtained by a dynamic cluster analysis of a large data base of known crystallographic structures. Successful applications of these algorithms to the prediction of known protein conformations are presented. PMID- 1892587 TI - Expression of HIV-1 in the cerebrospinal fluid detected by the polymerase chain reaction and its correlation with central nervous system disease. AB - The polymerase chain reaction (PCR) was used to detect HIV-1 sequences (gag, pol, and env) in the cerebrospinal fluid (CSF) and serum samples from 53 HIV-1 positive patients and the results correlated with clinical evidence of neurological disease. Twenty-three out of 24 patients with neurological disease had HIV-1-specific sequences in CSF compared with four out of 20 asymptomatic patients who had no evidence of neurological involvement. The detection of HIV RNA sequences by PCR in the CSF of HIV-positive patients may provide early, rapid and direct evidence of neurological involvement in asymptomatic subjects. PMID- 1892588 TI - Immunological and virological markers in individuals progressing from seroconversion to AIDS. AB - Six men were selected from a large cohort of homosexual men participating in a study on HIV infection that was followed from seroconversion to AIDS. The patients were studied retrospectively for immunological functions of T cells, T cell subset distribution and biological phenotype of HIV. A severe decrease in anti-CD3 monoclonal antibody (MAb)-induced T-cell proliferation at seroconversion was observed in two out of six men. After this acute phase, CD4+ T-cell numbers were in the normal range in the early asymptomatic period; the proliferative response was subnormal, whereas the capacity to generate cytotoxic T cells (CTL) was normal. From seroconversion on, CD4+CD29+ memory T-cell numbers were decreased to approximately 50% of normal values, which may contribute to loss of T-cell reactivity. In the asymptomatic phase only slow-replicating non-syncytium inducing HIV variants were observed. The T-cell proliferative response further declined with the depletion of naive CD4+ CD45RA+ T cells and CD4+ T-cell numbers started to decline. This second decrease in T-cell function coincided with the emergence of more rapidly replicating, often (four out of six) syncytium-inducing variants. At diagnosis of AIDS, T-cell proliferation and CD4+ T-cell numbers were extremely low in five out of six patients and CTL function had declined in three out of five individuals tested. Circulating CD8+ cells had gradually shifted to an immature CD38+CD28- phenotype. Our findings support the theory that HIV induced immune dysfunction allows for the emergence of virulent HIV variants associated with CD4+ cell loss and disease. PMID- 1892589 TI - HIV prevalence and risk behaviours for HIV transmission in South Australian prisons. AB - During the latter half of 1989, HIV prevalence in South Australian prisoners was 1.4%. The prevalence of HIV infection across the prison system did not change significantly during 1989 but there was clustering of HIV-infected prisoners in some prisons. Almost half the prisoners from all of the South Australian prisons agreed to participate in our studies, from which we estimate that about 42% of prisoners engage in risk behaviours at least once while incarcerated. Prisoners estimated that 36% of all prisoners inject drugs intravenously at some stage during their stay and that 12% engage in anal intercourse at least once. Interviews with former prisoners who had a history of intravenous drug use revealed that about half had injected themselves while in prison, 60% shared needles and most did not clean shared needles adequately. Most of these prisoners injected themselves once a month or less frequently. The conditions for spread of HIV within the prison system exist but at the current prevalence of infection, transmission can be expected to be infrequent. The opportunity exists now to improve and expand preventive measures. PMID- 1892590 TI - Trends in mortality among AIDS patients in Amsterdam, 1982-1988. AB - In this study we evaluated the survival of 515 AIDS patients diagnosed in Amsterdam between 1982 and 1988 and followed-up until April 1990. Non-resident patients survived for a shorter period than resident patients (median survival time 10 versus 16 months). Residents had a 1-, 2- and 3-year survival of 56.1, 33.0 and 17.2%, respectively. Heterosexual intravenous drug users tended to have a better survival than homosexual men, although this was not significant. The survival time was longer for AIDS patients less than 30 years of age at diagnosis and varied for the different clinical manifestations leading to AIDS diagnosis. We calculated the 1- and 2-year survival probability by year of diagnosis for patients initially presenting with a Pneumocystis carinii pneumonia (PCP). The 1 year survival improved greatly in 1986 and continued to rise in the following years. The 2-year survival was similar in 1986 and 1987 (26.8 versus 28.2%) but increased in 1988 (38.9%). We conclude that besides better clinical experience and diagnostic methods, this improvement in prognosis could be explained by the start of secondary prophylaxis for PCP in 1985 and the introduction of zidovudine therapy in 1987. PMID- 1892591 TI - Cross-reactivity on western blots in HIV-1 and HIV-2 infections. AB - To examine cross-reactivity of antibodies to heterologous antigens, on HIV-1 and HIV-2 Western blots, we tested sera from 1362 consecutive tuberculosis (TB) patients and 2127 consecutive blood donors. Specimens positive on enzyme-linked immunosorbent assay (ELISA) for HIV-1 or HIV-2 were further characterized by synthetic peptide-based tests, and tested by HIV-1- and HIV-2-specific Western blots. Dual serologic reactivity on synthetic peptide tests was proportionately more frequent in HIV-positive TB patients than in blood donors, and HIV-2 reactivity less frequent. Positive HIV-1 Western blots were seen in 73-83% of specimens specifically characterized as positive for HIV-2 on synthetic peptide tests. Cross-reactivity to HIV-2 Western blots by HIV-1-positive specimens was significantly more frequent in TB patients (35%) than in asymptomatic donors (9%; P less than 0.001). Using recently recommended criteria for HIV-2 Western blot interpretation (presence of two env bands) reduced the overall proportion of HIV 1-positive specimens having a positive HIV-2 Western blot from 27.5 to 16.4%, with [corrected] minimal effect on sensitivity in the diagnosis of HIV-2 reactivity on specimens positive on synthetic peptide tests. PMID- 1892592 TI - Toxicity and activity of purified trichosanthin. AB - Trichosanthin was purified from fresh Chinese root tubers of Trichosanthes kirilowii and evaluated for anti-HIV activity. Trichosanthin inhibited syncytium formation between infected H9 cells and uninfected Sup-T1 cells from 0.5 to 4 micrograms/ml. Trichosanthin also inhibited HIV replication in H9 and CEM-SS cells at 1 microgram/ml, but was toxic for MT-4 cells (HTLV-I-positive), at doses greater than 0.25 microgram/ml. This new purification procedure confirms the anti HIV activity of trichosanthin on some cell lines in different biological assays. PMID- 1892593 TI - AIDS-associated Kaposi's sarcoma in female patients. AB - Kaposi's sarcoma (KS) is very unusual in Caucasian women with AIDS. We conducted a retrospective survey of 12 female AIDS patients with KS, including 11 Caucasian women. HIV infection was thought to have been acquired after sexual contact, intravenous drug use (nine cases) or blood transfusion (three cases). In these patients KS was often the first manifestation of AIDS and showed an aggressive course. The disease was associated with a severe immunodeficiency (CD4 T lymphocyte count less than 100 x 10(6)/l in 50% of cases) and a poor prognosis. In four patients, lesions first developed on areas of sexual contact, supporting the hypothesis that KS is a sexually transmitted disease. PMID- 1892594 TI - Use of polymerase chain reaction for the early detection of HIV infection in the infants of HIV-seropositive women. AB - Forty-two infants of HIV-seropositive women were evaluated to determine the value of polymerase chain reaction (PCR) in the early detection of HIV infection. All infants less than 6 months old had a simultaneous PCR and culture for HIV. There was an 88% concordance between the two techniques. PCR results showed an excellent correlation with clinical outcome; no PCR-negative patient has subsequently been found to be infected. Occasional false-positive or equivocal PCR results did occur. There was one false-negative culture. PCR is a rapid and sensitive diagnostic test for the early diagnosis of HIV infection in infants at risk, but at present it should be performed in conjunction with other diagnostic tests and good clinical follow-up. PMID- 1892595 TI - Evaluation of saliva as a specimen for monitoring zidovudine therapy in HIV infected patients. AB - To facilitate studies of the pharmacokinetic properties of zidovudine, the relationship between plasma and salivary concentrations of the drug was studied, after oral dosage, in 10 HIV-infected patients. Zidovudine concentrations were determined in plasma, unstimulated mixed saliva and citric-acid-stimulated mixed saliva over a period of 3 1/2 hours by high-performance liquid chromatography. Correlation coefficients were r = 0.97 (P less than 0.0001) for stimulated saliva compared with plasma and r = 0.89 (P less than 0.0001) for unstimulated saliva, with average values in unstimulated saliva being 113.8 +/- 44.6% in plasma and 67.8 +/- 25.4% in stimulated saliva. Stimulated saliva values found to be 70% of the total reflected the concentration of the unbound drug in plasma. Except for a shorter half-life time (t1/2) in saliva, pharmacokinetic parameters showed a good correlation in the three types of specimen. These findings and the convenience of sample collection suggest that citric-acid-stimulated saliva might be an appropriate specimen for monitoring zidovudine therapy. PMID- 1892596 TI - The synthetic peptide from HIV increases functional activity of granulocytes in healthy subjects. AB - The influence of HIV lysate and eight synthetic peptides which are fragments of HIV proteins on the functional activity of polymorphonuclear neutrophils (PMN) was tested in 12 healthy subjects. PMN activity in nitroblue tetrazolium reduction (NBT test) and PMN chemiluminescence (CL) was studied. Only one peptide was found to result in a significant increase in NBT test on the whole blood. This was the oligopeptide (G-97) from the CD4-binding site of HIV-1 gp120. The increase of CL response of PMN in the presence of G-97 was revealed after only 15 min preincubation. The same effect in the presence of sera from healthy or infected patients at the persistent generalized lymphadenopathy stage was achieved by increasing the time of preincubation to 30 min. G-97 did not influence the proliferative activity of lymphocytes. PMID- 1892597 TI - An inhibition enzyme immunoassay using a human monoclonal antibody (K14) reactive with gp41 of HIV-1 for the serology of HIV-1 infections. AB - An inhibition enzyme immunoassay (IEIA), using a human monoclonal antibody (K14) reactive with gp41 of HIV-1, was evaluated for its applicability to the serology of HIV-1 infections. Using panels of serum samples from seronegative and confirmed HIV-1-seropositive individuals, it was shown that all the HIV-1 positive samples in a panel from The Netherlands and 97% of the HIV-1-positive samples from Tanzania were identified by this IEIA. Six per cent of the IEIA positive samples from Tanzania could not be confirmed in other assays. Testing of serial dilutions of serum samples from African individuals with confirmed HIV-1, HIV-2 or HIV(ANI70) infections in the K14 IEIA, indicated that a HIV-1-specific assay based on this principle may be developed. PMID- 1892598 TI - HIV in prisons: the pragmatic approach. PMID- 1892599 TI - Isolation of HIV from whole blood. PMID- 1892600 TI - Atypical leishmaniasis in an HIV-2-seropositive patient from Guinea-Bissau. PMID- 1892601 TI - Multifocal splenic abscesses caused by Mycobacterium tuberculosis in HIV-infected drug users. PMID- 1892602 TI - AIDS and diabetic retinopathy. PMID- 1892603 TI - HIV-1 in Somalia: prevalence and knowledge among prostitutes. PMID- 1892604 TI - A simple scoring system to assess risk of hematological side effects in zidovudine recipients. PMID- 1892605 TI - Bacterial proteins cytotoxic to HIV-1-infected cells. PMID- 1892606 TI - Fed-state effects on zidovudine absorption. PMID- 1892607 TI - Ketoconazole-responsive tonsillar infection due to Histoplasma capsulatum in an HIV-1-seropositive individual. PMID- 1892609 TI - [Description of an automated system for reading, by means of imaging, antibiotic inhibition circles]. PMID- 1892608 TI - Liquid chromatographic determination of acyclovir. AB - An easy and precise HPLC method was developed to determine acyclovir in liophilized vials and ointments. The described procedure detects guanine which can be present in raw material as a synthetic contaminant or a degradation product. The method proved to be simple and accurate. PMID- 1892610 TI - [Morphological and structural aspects of solid drug forms]. AB - As a follow-up to a previous article, where the characteristics of the solid state and the X-ray properties and pharmaceutical applications were described ("X rays, diffractometry in the analysis of drugs and pharmaceutical forms", Boll. Chim. Farm. 128, 149; 1989), the Author has more specifically considered the so called "variants" of a drug's solid state, which can be employed in the dosage forms (polymorph, solvate, crystalline habitus, amorphous). In addition, mention is made of drugs' isomorphism and the difference between a polymorphic solvate and the polymorphism of a solvate is clearly stressed. PMID- 1892612 TI - Misleading results in studying pharmacodynamic interaction with oral anticoagulant. AB - We described an experimental condition, in which the i.p. administration of rats of irritants produces a misleading increase of the anticoagulant effect of warfarin. Group of 10 adult Wistar rats were treated i.p. or i.v. with HCl 0.1N plus warfarin p.o.; 24 hr after warfarin administration, prothrombin time was determined on citrate blood specimens and the animals were submitted to autopsy. When HCl is given i.p., a significant increase of prothrombin time is observed. On the contrary following i.v. administration no interference with the anticoagulant effect of warfarin is observed. Abdomen exploration of rats shows the presence of serum exudate following i.p. but not i.v. administration of HCl. The synergistic effect of i.p. administration of HCl on anticoagulant effect of warfarin appears an experimental artifact, probably attributable to a non specific local irritating effect. This result stresses the need of caution in interpreting animal data indicating a synergism with oral anticoagulant. PMID- 1892611 TI - Synthesis and pharmacological evaluation of pyrazolopyrimidobenzoxazole and pyrazolopyrimidobenzothiazole derivatives. AB - As a part of research on polieterocycles compounds with condensed nuclei, containing pyrimidine ring, as potential antalgic/anti-inflammatory drugs, pyrazolopyrimidobenzoxazole and pyrazolopyrimidobenzothiazole were prepared and tested. None of the substances shows significative activities in vivo. PMID- 1892613 TI - [Stability at different pH of polyene antibiotics derived from partricin]. AB - The degradation of a new semisynthetic polyene antibiotic partricin A dimethylamino ethylamide diaspartate (SPA-S-717) at 37 degrees C in water at different pH is studied. It is found to be sensitive to acidic pH and much less sensitive near neutrality. Then a linear relation between pH and logarithm of reaction rate constant is detected. This fact therefore can give some directions as regards the drug somministration in view of pharmacological and clinical trials. PMID- 1892614 TI - Passing the torch. PMID- 1892615 TI - Postblepharoplasty ectropion. Prevention and management. AB - Lower-eyelid malposition is one of the more serious complications encountered following lower-lid blepharoplasty, ranging in severity from mild lower-lid retraction to frank ectropion with marked lower-lid eversion. We define a grading system for postblepharoplasty lid malposition based on the severity of lower-lid retraction. In a critical review of 111 patients who underwent lower-lid blepharoplasty between January 1985 and January 1990, 15% were thought to have some degree of lower-lid retraction. Presence of lid laxity preoperatively and increasing amounts of skin excision at surgery were significant factors in the development of malposition. Placement of orbicularis suspension sutures tended to decrease the incidence of lid retraction. No patients had frank ectropion; however, three patients with grade 2 or 3 malposition required a secondary surgical procedure for correction. All three patients had resolution of their symptoms and good cosmetic results using standard treatment methods. A literature review and discussion of the causes, sequelae, and management of post-operative ectropion is presented as a reminder to surgeons performing blepharoplasty. Avoidance of this entity by appropriate preoperative assessment is emphasized, along with conservative operative technique. These factors combined are essential for the successful outcome of lower-lid blepharoplasty. PMID- 1892616 TI - Laryngeal airway resistance. The relationships of airflow, pressure, and aperture. AB - In the surgical treatment of the paralyzed larynx, a compromise often needs to be made between an orifice size needed to preserve voice and that needed for adequate inspiratory airflow rates. To assess the negative pressures needed to generate normal airflows across a narrowed vocal cord aperture, we measured pressure and flow changes across cadaveric larynges while altering aperture size. Best-fit quadratic equations for each aperture area selected were derived and showed that if the aperture were 0.5 cm2 or less, the resistance to normal breathing would be significantly increased. Aperture sizes of 0.67 cm2 or greater are not associated with such an increase in resistance. PMID- 1892617 TI - A new technique for quantitative measurement of laryngeal videostroboscopic images. AB - The objective measurement of laryngeal function and pathophysiology is one of the goals of current laryngeal research. We describe a new computerized tool for voice analysis systems that allows the quantitative analysis of individual videostroboscopic images. We describe this new technique compared with previous methods of videostroboscopic image analysis and discuss its clinical and research applications. PMID- 1892618 TI - The causes and complications of late diagnosis of foreign body aspiration in children. Report of 210 cases. AB - Late diagnoses of foreign body aspiration were defined as occurring beyond 3 days between the aspiration of the foreign body, or onset of symptoms, and correct diagnosis. We reviewed a total of 210 children with late diagnosis of foreign body aspiration. The causes creating late diagnosis of foreign body aspiration in children were as follows: (1) parental negligence (106/210, 50%); (2) misdiagnosis by the fellow professionals and pediatricians (39/210, 19%); (3) the normal chest roentgenographic findings (29/210, 14%); (4) lack of typical symptoms and signs (26/210, 12%); (5) mismanagement (8/210, 4%); and (6) a negative bronchoscopic finding (2/210, 1%). The most common complications encountered were obstructive emphysema (77/186, 41%), mediastinal shift (63/186, 34%), pneumonia (43/186, 24%), and atelectasis (33/186, 18%) in 186 patients who underwent a chest roentgenographic examination. The incidence of major complications was 64% (48/75) in the children who were diagnosed within 4 to 7 days; however, the complication rate was 70% (39/56) in those with a delay in diagnosis of 15 to 30 days, and 95% (20/21) in the cases with a delay in diagnosis of over 30 days after aspirating the foreign bodies. PMID- 1892619 TI - The prognostic value of endotracheal tube-air leak following tracheal surgery in children. AB - In an effort to determine if the endotracheal tube-leak pressure has prognostic value in relation to a successful outcome after one-stage laryngotracheal reconstruction or cricoid split surgery, a retrospective analysis was performed on 17 children who had undergone such surgery. The daily leak pressures, length of intubation, and ultimate outcome of attempts at extubation were noted. One hundred percent of patients with a leak pressure of less than 20 cm H2O on the day before extubation were successfully extubated. In contrast, the failure rate was 100% in children extubated with a leak of greater than 30 mm H2O. The difference between these two groups was statistically significant (chi 2, 13.03). Sixty percent of patients with leak pressures in the range of 21 to 30 cm H2O were successfully extubated. The endotracheal tube-leak pressure is a parameter that has prognostic value, and should be considered in determining when to extubate children who have undergone tracheal reconstructive surgery. PMID- 1892621 TI - Use of tap water and disinfection practices in outpatient settings. A survey of otolaryngologists. AB - A survey of otolaryngologists belonging to the American Academy of Otolaryngology Head and Neck Surgery was conducted to estimate the frequency of tap water use during otologic examinations and to assess methods used for disinfection of otologic instruments in outpatient settings. Questionnaires were returned by 516 persons residing in 49 states. Tap water was used commonly for rinsing suction tips while suctioning patients even with tympanic membrane perforations (45%). Most respondents (87%) reported that their otologic instruments undergo either high-level disinfection or sterilization between patient examinations; however, only 63% to 67% of respondents reported adequate duration of treatment times (high-level disinfection, greater than or equal to 30 minutes; boiling, greater than or equal to 5 minutes; or autoclaving, greater than or equal to 20 minutes). The risk posed by the use of tap water during otologic examinations and the need for adequate disinfection of otologic instruments between patient examinations are presented. PMID- 1892620 TI - Actinomycosis in obstructive tonsillar hypertrophy and recurrent tonsillitis. AB - A quantitative analysis of adenoid and tonsillar specimens from 460 patients was performed. The patients underwent tonsillectomy or adenotonsillectomy for either recurrent tonsillitis or obstructive tonsillar hypertrophy. Histologic preparations revealed Actinomycetes as statistically more prevalent in the obstructive population. The presence of Actinomycetes in the adenotonsillar core of this diagnostic group may indicate an etiologic role for this organism in tonsillar and adenoidal hypertrophy. PMID- 1892622 TI - Oral vaccine therapy for pneumococcal otitis media in an animal model. AB - We investigated whether mucosal IgA response in the middle ear cavity against Streptococcus pneumoniae type 19F is enhanced by use of enteric capsules, and whether the resulting mucosal immunity can prevent pneumococcal otitis media. Adult Hartley guinea pigs were employed. With intratympanic inoculation of 10(5) and 10(6) live S pneumoniae, the occurrence of pneumococcal otitis media significantly decreased in guinea pigs that received intraduodenal and intragastric immunization by enteric capsules. In these guinea pigs, the values of salivary IgA antibody titers against S pneumoniae were significantly greater, and histologic changes of the middle ear mucosa were also slighter than those of control guinea pigs. These findings indicate that oral vaccination by enteric capsules elicits mucosal IgA responses, as well as intraduodenal immunization, to prevent pneumococcal otitis media. These results suggest the possibility of clinical application of oral vaccination by enteric capsules for the prevention of middle ear infection. PMID- 1892623 TI - Complications following ventilation of the middle ear using Goode T tubes. AB - This is a 3.5-year retrospective review on the insertion of 210 Goode T tubes into 182 ears of 93 patients. Otorrhea was noted postoperatively in 35.2% of the ears treated, with chronic drainage lasting longer than 4 months developing in more than 7% of the cases. Perforations were found in 34 ears (18.7%) following removal or extrusion of the T tubes; in 13 (7.1%) of these patients, chronic perforations requiring tympanoplasties developed. The literature was screened for additional studies addressing the complications associated with tympanostomy tubes. The documented incidence of perforations between conventional tubes and Goode T tubes was emphasized, and comparisons were made. Our findings indicate that, even with the immediate placement of paper patches following removal of all Goode T tubes, the percentage of tympanic membrane perforations resulting from the use of Goode T tubes is significantly greater than previously reported. PMID- 1892624 TI - Facial weakness. A comparison of clinical and photographic methods of observation. AB - The search for an internationally acceptable facial grading system has resulted in an assessment of existing methods by several investigators. These studies were based on observations of video film taken of patients with varying degrees of facial malfunction. Although the grading systems were evaluated, the use of videotape has never been compared with clinical examination and its suitability for this type of work is, therefore, unknown. We used nine facial grading systems to compare the results of clinical observation with those of photographic methods of presentation. The latter included videotape, photographic slides, and a combination of the two. The correlation between clinical examination findings and findings of any of the photographic methods was poor, suggesting the need for a standard form of presentation when grading patients. The most consistent results were found with either clinical examination or photographic slides; videotape was the least reliable. PMID- 1892625 TI - Antral choanal polyp presenting as obstructive sleep apnea syndrome. AB - Obstructive sleep apnea syndrome (OSAS) in children is commonly caused by adenotonsillar hypertrophy. The diagnostic criteria of OSAS in children are not so well delineated as in adults. We report the first case of antral choanal polyp presenting as OSAS in a 10-year-old boy that initially presented to the child psychiatry service for behavior disturbance, enuresis, and daytime somnolence. Overnight electroencephalogram sleep study revealed events consistent with OSAS. Multiple inhalant allergies, chronic maxillary sinusitis, and obstructive adenoid hypertrophy were diagnosed by the allergy and otolaryngology services. The child was scheduled for adenoidectomy when his sleep apnea symptoms persisted following antimicrobial therapy. Examination under anesthesia revealed a normal adenoid bed and a large left antral choanal polyp. Polypectomy was performed as dictated by parental consent. Postoperatively treatment with an intranasal steroid was begun. However, polypoid nasal mucosa recurred in 2 months and a Caldwell-Luc procedure was performed. Subjective reports following surgery indicated improvement in daytime irritability, attention, and mood. A follow-up overnight electroencephalogram sleep study confirmed resolution of OSAS. PMID- 1892626 TI - Mandible reconstruction with vascularized bone grafts. A histologic evaluation. AB - To our knowledge, a histologic evaluation of bone healing after mandible reconstruction with vascularized human bone grafts has not been previously reported. Serial sections through both the decalcified graft and the junction between mandible and graft were evaluated in four patients who required surgical removal of their reconstructed mandibles. A failed scapular bone graft that had been wrapped within a pectoralis major myocutaneous flap for salvage following pedicle thrombosis showed markedly resorbed but viable bone with a fibrous union to the native mandible. Viable vascularized grafts without evidence of ongoing resorption characterized an iliac osteocutaneous bone graft and two scapula osteocutaneous grafts that healed with continuity of healthy bone between graft and mandible. Observations from the evaluation of these specimens are made regarding bone circulation, bone union, and bone graft survival as they occur clinically. Implications regarding the techniques of bone plating and indications for use of vascularized bone in mandible reconstruction are discussed. PMID- 1892627 TI - Pathologic quiz case 1. Benign Schwannoma of tongue. PMID- 1892628 TI - Pathologic quiz case 2. Salivary epithelial-myoepithelial carcinoma (clear cell carcinoma of the salivary gland). PMID- 1892629 TI - Mondini dysplasia is not associated with meningitis and cerebrospinal fluid fistula. PMID- 1892630 TI - Decision analysis in head and neck cancer. PMID- 1892631 TI - Improving diagnostic accuracy of cervical metastases with computed tomography and magnetic resonance imaging. PMID- 1892632 TI - The internal elastic lamina in the basilar artery and its possible significance for intimal thickening. A morphometric study. AB - The degree of intimal thickening, folding of the internal elastic lamina (IEL) and luminal radius/wall thickness ratio (RWR) have been compared between predilectional sites and a non-predilectional site for atherosclerosis in human basilar arteries. The findings are compatible with the hypothesis that a low degree of folding and a high RWR facilitate intimal thickening. A negative correlation between the fold index and intimal thickening index and a positive correlation between RWR index and intimal thickening index were found. Predilectional areas also have lower fold indices and higher RWR in younger subjects prior to any intimal thickening development. PMID- 1892633 TI - Genotypic heterogeneity of Flavobacterium group IIb and Flavobacterium breve demonstrated by DNA-DNA hybridization. AB - DNA-DNA hybridization studies on 42 stains presumptively identified as members of Flavobacterium group IIb and Flavobacterium breve indicated pronounced genotypic heterogeneity within these taxa. Three large groups highly related to the type strains of F. gleum, F. indologenes and F. breve respectively, and eight small groups were found. The group containing the type strain of F. breve was phenotypically indistinguishable from another genomic group, and these two groups were significantly separated from the other flavobacteria studied. The other nine genomic groups, representing Flavobacterium group IIb, could not with certainty be differentiated from each other by phenotypic characteristics, and there is no evidence indicating that these genomic groups differ from each other with respect to pathogenicity or ecology. Thus, it is suggested that for the time being the name "Flavobacterium group IIb" rather than specific epithets continue to be used for these bacteria. PMID- 1892634 TI - Shigella flexneri infection: a histopathologic study of colonic biopsies in monkeys infected with virulent and attenuated bacterial strains. AB - Macaca fascicularis monkeys were orally infected with live virulent Shigella flexneri wild-type strains of either serotype Y (S. flexneri SFL1), 2a (S. flexneri M4243) or 1b (S. flexneri SFL27). Clinical signs of shigellosis varied from mild watery diarrhea (SFL1) to dysentery (M4243, SFL27), with a fatal outcome in two monkeys (SFL27). Colonoscopy showed slight pathologic changes in monkeys infected with SFL1, and pronounced changes in monkeys infected with SFL27. In colonic biopsies the most severe acute inflammation, with surface epithelial erosions and ulcerations, was seen after infection with SFL27, followed by SFL1, and M4243. The live S. flexneri serotype Y vaccine strain SFL114, derived from SFL1 and attenuated because of an inactivated aroD gene and hence auxotrophic for p-aminobenzoic acid, caused no diarrheal illness in 14 monkeys. In colonic biopsies, SFL114 only elicited a slight acute inflammatory reaction. Vaccinated monkeys were protected against clinical disease when challenged with any one of the three virulent S. flexneri wild-type strains. Histopathologically, the acute inflammation was of less intensity than that seen in non-vaccinated monkeys. A good correlation between clinical signs, endoscopic findings and the degree of acute inflammation was demonstrated for monkeys vaccinated with SFL114 and challenged with either SFL1 or SFL27. PMID- 1892635 TI - The topographic distribution of lymphocytic gastritis in gastrectomy specimens. AB - Forty-eight entire gastrectomy specimens received consecutively at this Department were cut into blocks for histologic examination. Focal or more extended areas of chronic gastritis (i.e. superficial or atrophic with or without intestinal metaplasia) were present in all 48 specimens. In addition, two of the 48 specimens had a large number of lymphocytes in the surface and foveolar epithelium of the mucosa. In the literature the latter is regarded as "lymphocytic gastritis". Lymphocytic gastritis was found in all 156 sections obtained from the two specimens. This lympho-epithelial phenomenon was present even in areas lacking chronic inflammation in the subjacent lamina propria mucosae. From our results it would appear that while chronic gastritis has a focal or a regional topographic distribution, lymphocytic gastritis includes the entire surface-foveolar epithelium of the gastric mucosa. PMID- 1892636 TI - Experimental candidosis in pregnant mice. AB - Pregnant mice were challenged intravenously with doses of 1 x 10(3)-1 x 10(7) Candida albicans blastospores, and from postmortem histopathology it was found that C. albicans had a propensity for localization in the murine placenta. At the highest dose, blastospores, hyphae and pseudohyphae were randomly located in the foeto-placental units, whereas proliferation of fungi at lower doses started in the rim of the placental disc, after which it spread along Reichert's membrane and/or the splanchnopleure, eventually attacking the foetal skin. These findings are analogous to our previous observations on the nature of Aspergillus fumigatus infection in pregnant mice. PMID- 1892637 TI - Glomerular tip lesions in renal biopsies with focal segmental IgM. AB - Renal biopsies in which immunohistologic examination had shown the presence of glomerular focal segmental IgM were reviewed in order to investigate the histology and clinical course in these patients. Among 19 such biopsies, 12 had focal segmental glomerulosclerosis (FSGS), whereas seven had only so-called glomerular tip lesions (GTL). GTL also occurred moreover in four of the patients with FSGS. Clinical data suggest a somewhat milder course of disease in the seven patients with GTL as the sole lesion than in the patients of the FSGS group. The nature of GTL is at present unclear. We suggest that GTL may be an initial stage of FSGS, being a lesion that may or may not develop towards FSGS in its typical form. Regardless of its origin, attention is directed to the GTL as a characteristic histologic glomerular lesion, which may be the only significant histologic change in the renal biopsy from a patient with nephrotic syndrome or severe proteinuria. PMID- 1892638 TI - Agarose method for the preparation of isolated glomeruli from human renal biopsies. AB - We present a technique using glomeruli which are removed by dissection from human renal biopsies and processed for transmission electron microscopy (TEM). Firstly, glomeruli are dissected and isolated from the specimen. Secondly, the collected glomeruli are embedded in agarose with a low gelling temperature. Finally, the embedded glomeruli are processed in the same way as whole pieces of tissue using standard methods for TEM. We have successfully prepared several hundred specimens using this simple and reliable technique. Provided that care is taken to prevent mechanical damage to the glomeruli during collection, no severe artifacts are introduced into the tissue. Even a single glomerulus can be isolated and processed in this way. PMID- 1892639 TI - Cross-reactive Legionella antigens and the antibody response during infection. AB - In order to define cross-reactive Legionella antigens suitable for diagnostic purposes, we investigated sonicate antigens from two Legionella species, including two serogroups of L. pneumophila. The antigens were reacted with heterologous and homologous rabbit antisera in Western blot. Sera from seven patients with culture-verified L. pneumophila infection and nine patients with serologically confirmed L. micdadei infection were also investigated for reactivity with the corresponding antigens. Among the cross-reactive Legionella antigens defined, non-specific reactivity in patients' sera with the 58-kDa common antigen (CA) was noted. Specific reactions were observed with the Legionella flagellum antigen and with the macrophage infectivity potentiator (Mip) protein; with both antigens, however, the reactive sera were too few to suggest the use of a single antigen in a diagnostic test. PMID- 1892640 TI - Pleomorphic adenoma of the breast. Case report. AB - A clinicopathologic study of a pleomorphic adenoma of the breast is presented and attention is drawn to a previously unreported association with a cyst. Malignancy was strongly suspected in the light of radiologic features. Immunohistochemistry stresses the similarity between pleomorphic adenoma of salivary gland and breast. A common histogenesis of the two entities is also suggested. Ontogenetic links of both glands are mentioned. PMID- 1892642 TI - Ferret tracheal epithelial cells grown in vitro are resistant to lethal injury by activated neutrophils. AB - Airway inflammation is often accompanied by accumulation of polymorphonuclear leukocytes (PMN) as well as epithelial sloughing. To determine whether PMN contribute to epithelial damage in inflammatory states, we examined the interaction of PMN and tracheal epithelial cells in culture. Ferret tracheal epithelial (FTE) cells were grown in primary culture on collagen-coated multiwell dishes. Confluent monolayers were loaded with [51Cr]O4 and exposed to resting and activated neutrophils. There was no significant increase in cell death as assessed by [51Cr]O4 release over 8 h of exposure, at effector (PMN)-to-target cell (epithelial cell) ratios up to 90:1, whether PMN were activated by maximal activating concentrations of phorbol myristate acetate or formylmethionylleucylphenylalanine with or without cytochalasin B. This result was confirmed by using a [3H]leucine release assay as well as by uptake of a supravital dye. However, exposure of FTE cells to activated PMN for 4 h resulted in separation of adjacent cells and formation of gaps in the monolayer, without significant detachment of epithelial cells from the dish. Gap formation was prevented by alpha 1-antitrypsin, N-methoxysuccinyl-Ala-Ala-Pro-Val chloromethylketone, or 10% serum, was mimicked by PMN elastase (24 micrograms/ml), but not by hydrogen peroxide in concentrations up to 10 mM, or superoxide generated by xanthine/xanthine oxidase, and was reversible within 24 h of removal of elastase and exposure to fresh medium. We conclude that activated PMN do not kill FTE cells in culture. However, disruption of the epithelial cell monolayer probably by a proteolytic mechanism can result from exposure to activated PMN and may allow alteration of the epithelial barrier during airway inflammation. PMID- 1892641 TI - Alveolar basement membrane: molecular properties of the noncollagenous domain (hexamer) of collagen IV and its reactivity with Goodpasture autoantibodies. AB - The noncollagenous domain hexamer of collagen IV from bovine alveolar basement membrane was excised with bacterial collagenase, purified under nondenaturing conditions, and characterized. The hexamer is comprised of four distinct subunits [alpha 1(IV)NC1, alpha 2(IV)NC1, alpha 3(IV)NC1, and alpha 4(IV)NC1]. Each subunit exists in both monomeric and dimeric (disulfide-crosslinked) form, and both monomers and dimers have charge isoforms. Certain dimers also contain nonreducible crosslinks. The alpha 3(IV)NC1 subunit, in both the monomeric and dimeric form, reacts with Goodpasture (GP) antibodies. The GP epitope is sequestered within the hexamer and becomes reactive with antibody upon exposure with protein denaturants. These results reveal that the alveolar basement membrane hexamer is identical to the hexamer from glomerular basement membrane with respect to subunit composition, identity of subunits reacting with GP antibodies, and sequestration of the GP epitope but differs greatly in the relative amount of the GP-reactive subunit and the degree of disulfide and nondisulfide crosslinking of subunits. This study leads to the conclusion that pulmonary hemorrhage associated with GP syndrome is mediated by the same autoantibody that mediates the glomerulonephritis, namely anti-collagen [alpha 3(IV)] antibody. PMID- 1892643 TI - The response of guinea pig airway epithelial cells and alveolar macrophages to environmental stress. AB - Cells lining the respiratory tract form an interface between the organism and the external environment and are repeatedly exposed to physical, chemical, and metabolic stresses. We examined the response of cultured guinea pig tracheal epithelial cells and alveolar macrophages to various forms of stress, including clinically and environmentally relevant metabolic stresses such as ozone and acid exposure. Classic stress treatments such as heat shock and sodium arsenite treatment induced the synthesis of 28, 32, 72, 73, 90, and 110 kD stress proteins similar to those observed in other cell types. In contrast, no significant changes in the pattern of protein synthesis were detected after exposure to ambient concentrations of ozone, although ozone exposure caused significant cytotoxicity to both cell types. Another potent oxidant, hydrogen peroxide, similarly did not induce appreciable stress protein synthesis. However, surface acidification of tracheal epithelial cells and alveolar macrophages caused the induction of 72 and 78 kD stress proteins. While stress proteins may play a role in the response of respiratory cells to certain injuries such as hyperthermia and surface acidification, they may not be important in the defense against ozone or other forms of oxidative injury. PMID- 1892644 TI - Production of tumor necrosis factor-alpha by blood and lung mononuclear phagocytes from patients with human immunodeficiency virus-related lung disease. AB - Tumor necrosis factor-alpha (TNF) is a cytokine involved in the pathogenesis of shock and in granuloma formation, tissue necrosis, and fibrosis, in many organ systems, including the lung. It has been suggested that cells from patients infected by the human immunodeficiency virus (HIV + ve) are primed for TNF release. We postulated that TNF release from the alveolar macrophages (AM) of such patients with lung disease might lead to their observed pulmonary dysfunction. We present data confirming that peripheral blood monocytes (PBM) and demonstrating that AM from HIV + ve patients with pulmonary manifestations show significantly greater TNF production than those from HIV-negative (HIV - ve) subjects. In addition, we found sequentially significant increases in TNF production from AM and PBM of HIV + ve patients with no pathogens detected at bronchoscopy (NB), bacterial pneumonia (BP), and those with Pneumocystis carinii pneumonia (PCP). The overall TNF levels were greater from AM than PBM in all groups other than spontaneous production from HIV - ve subjects. Adherent populations of PBM and AM were incubated for 4 h with lipopolysaccharide (10 micrograms/ml) or control medium alone. Cell-free supernatants were examined for the presence of TNF using an immunoassay. The TNF levels (mean +/- SD) in IU/ml from stimulated PBM of the PCP, BP, NB, and control groups, respectively, were 186 +/- 36, 140 +/- 30, 95 +/- 18, and 55 +/- 10 and the spontaneous levels were 123 +/- 25, 100 +/- 22, 75 +/- 24, and 11 +/- 5.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1892645 TI - Translation of messenger RNA from canine tracheal epithelial cells: identification of mucin core protein. AB - A high-molecular-weight mucin (Mr approximately 11.0 x 10(6)) was purified from canine tracheal pouch secretions. The mucin was deglycosylated by treatment with trifluoromethane sulfonic acid for 8 h at 8 degrees C and subsequently with alpha N-acetylgalactosaminidase. These treatments almost completely removed the carbohydrate moieties. The amino acid compositions of the deglycosylated and native mucins were similar, indicating that the deglycosylation procedure used did not cause notable degradation of the protein core. Antiserum specific for deglycosylated canine tracheal mucin was produced by immunization of rabbit with the antigen. RNA was isolated from fresh canine tracheal epithelial cells by extraction with guanidine isothiocyanate/hydrochloride and further fractionated by chromatography on oligo(dT)-cellulose to yield poly(A)+ RNA. The poly(A)+ RNA was translated in a rabbit reticulocyte cell-free translation system using [35S]methionine and [3H]leucine as radiolabels. The translation products were analyzed by gel electrophoresis and fluorography before and after immunoprecipitation with the antiserum to deglycosylated mucin. A labeled product of molecular weight 72,000 was present in the immunoprecipitate. When canine liver poly(A)+ RNA was used as control, no radioactivity above background was detected in the immunoprecipitate. It is concluded that the primary translation product of the canine tracheal epithelial cells is a 72,000-D protein and the monomer subunit of the mucin is about 167,000 D. Thus, in the native state, the canine tracheal mucin consists of several associating subunits. PMID- 1892646 TI - Increased production and immunohistochemical localization of transforming growth factor-beta in idiopathic pulmonary fibrosis. AB - Transforming growth factor-beta (TGF-beta) can regulate cell growth and differentiation as well as production of extracellular matrix proteins. Elevated production of TGF-beta has been associated with human and rodent chronic inflammatory and fibrotic diseases. Using immunohistochemical staining, we have examined lung sections of patients with advanced idiopathic pulmonary fibrosis (IPF), a disease characterized by chronic inflammation and fibrosis and demonstrated a marked and consistent increase in TGF-beta production in epithelial cells and macrophages when compared to patients with nonspecific inflammation and those with no inflammation or fibrosis. In patients with advanced IPF, intracellular staining with anti-LC (1-30) TGF-beta antibody was seen prominently in bronchiolar epithelial cells. In addition, epithelial cells of honeycomb cysts and hyperplastic type II pneumocytes stained intensely. Anti CC (1-30) TGF-beta antibody, which reacts with extracellular TGF-beta, was localized in the lamina propria of bronchioles and in subepithelial regions of honeycomb cysts in areas of dense fibroconnective tissue deposition. The close association of subepithelial TGF-beta to the intracellular form in advanced IPF suggests that TGF-beta was produced and secreted primarily by epithelial cells. Because of the well-known effects of TGF-beta on extracellular matrix formation and on epithelial cell differentiation, the increased production of TGF-beta in advanced IPF may be pathogenic to the pulmonary fibrotic and regenerative responses seen in this disease. PMID- 1892647 TI - Indices of oxidative stress in hamster lung following exposure to cobalt(II) ions: in vivo and in vitro studies. AB - Cobalt, a metal with numerous industrial applications, has been associated with lung disease, an extreme form of which is an interstitial fibrosis. The biochemical mechanisms underlying this toxicity are not understood. In vitro studies have suggested that cobalt(II) ions are able to generate reactive oxidant species (possibly hydroxyl radical) in a reaction with hydrogen peroxide, and we have hypothesized that the occurrence of such an event in lung tissue, and the subsequent development of oxidative damage, may contribute to this pulmonary toxicity. The intratracheal instillation of CoCl2 into hamster lungs resulted after 3 h in decreased levels of reduced glutathione and increases in levels of oxidized glutathione and in the activity of the pentose phosphate pathway. These changes, which are compatible with the generation of oxidative stress, were reversed by 48 h at low Co2+ doses (1.0 to 1,000 micrograms/kg). Irreversible changes at higher doses coincided with the onset of pulmonary edema. Incubation of lung slices with CoCl2 (0.1 to 10 mM) resulted in time- and Co2+ concentration dependent increases in levels of oxidized glutathione and protein-mixed disulfides and a decrease in reduced glutathione. A concentration-dependent stimulation of the pentose phosphate pathway was also observed. These changes preceded the detection of overt cell toxicity, as assessed by various biochemical parameters. These data indicate that thiol oxidation constitutes an early event in the pulmonary toxicity of cobalt(II) ions and are compatible with the hypothesis that the generation of oxidative stress may be of significance to the toxic process. PMID- 1892648 TI - Novel integrin alpha and beta subunit cDNAs identified in airway epithelial cells and lung leukocytes using the polymerase chain reaction. AB - The integrins are a large group of cell surface glycoproteins that mediate cell matrix and cell-cell adhesive interactions. Integrins play a role in normal lung development, in host defense against pulmonary infection, and in the pathogenesis of the adult respiratory distress syndrome. Integrins are heterodimers consisting of one alpha subunit and one beta subunit. We identified consensus sequences within integrin subunits and used oligonucleotide primers based on these sequences to amplify cDNA by the polymerase chain reaction (PCR). We previously reported the use of this homology PCR technique for the identification of one novel integrin beta subunit, beta 6, from guinea pig airway epithelial cells. Here we demonstrate that primers based on alpha subunit consensus sequences can also be used for homology PCR. We have used the alpha and beta subunit primers to amplify and clone a large variety of integrin partial cDNAs from several cell types and species. Comparison of the deduced amino acid sequences reveals a high degree of cross-species conservation (86 to 98% identity). One alpha subunit (identified in guinea pig airway epithelial cells) and one beta subunit (identified in rabbit leukocytes obtained by bronchoalveolar lavage and in human and mouse leukocyte cell lines) have novel sequences that are related to but clearly distinct from all previously reported integrin sequences (24 to 61% identity). These novel cDNAs are very likely to encode previously unsequenced integrin subunit proteins that are expressed in the lung. Homology PCR is a powerful technique for the identification of known and novel integrin alpha and beta subunit cDNAs in cells from the lung and other organs. PMID- 1892649 TI - Evidence for different human tracheobronchial mucin peptides deduced from nucleotide cDNA sequences. AB - Highly glycosylated regions or glycopeptides were obtained by proteolysis of human tracheobronchial mucins. They were chemically deglycosylated and the resulting products were used to raise a rabbit antiserum. This antiserum specifically recognized the superanuclear region of respiratory and colonic goblet cells as areas around and below the nucleus of mucin-secreting cells in tracheobronchial mucous glands. A lambda gt11 cDNA library constructed from human tracheobronchial mucosa was screened with this antiserum. Ten positive clones were obtained from screening half of the library (about 10(6) recombinants). The antibodies were purified by absorption to each positive clone; some purified antibodies were specific for goblet cells and others recognized both goblet and mucous cells, indicating that there is differential cellular expression of mucin peptides. The total or partial amino acid sequences deduced from these cDNA clones could be classified into three groups. The first group contained repetitive sequences of eight amino acid residues, almost perfectly identical, and in different arrangements. The second type exhibited homology at their amino and carboxy-terminal ends. The last group had no distinctive feature except for a high content of hydroxy amino acids typical of mucins. Five different clones could correspond to the carboxy-terminal end of tracheobronchial apomucins. These results indicate that human tracheobronchial apomucins consist of a family of different proteins. PMID- 1892650 TI - Hypersensitivity pneumonitis: whole Micropolyspora faeni or antigens thereof stimulate the release of proinflammatory cytokines from macrophages. AB - Hypersensitivity pneumonitis (HP) is an allergic granulomatous interstitial lung disease resulting from a reaction of selected individuals to repeated inhalations of certain antigens. HP is characterized by chronic inflammation, and the development of the disease seems to be immunologically mediated. In farmer's lung, the source of provoking antigen has been found to be actinomycetes such as Micropolyspora faeni. In this study, we show that M. faeni, or antigens thereof, stimulate strong release of proinflammatory cytokines from blood monocytes and alveolar macrophages obtained from nonfarmer volunteers and naive mouse peritoneal macrophages. Interleukin-1 (IL-1) was produced by human alveolar macrophages and murine peritoneal macrophages in response to whole M. faeni and antigens thereof. IL-1 activity was detected in the supernatants at 12 h of incubation and was maximal by 24 to 36 h (200 to 400 U/ml of IL-1). A rabbit antiserum to IL-1 alpha and IL-1 beta neutralized the thymocyte-stimulating activity of the supernatants. Moreover, M. faeni (1 to 100 micrograms of antigen) elicited a strong secretion of tumor necrosis factor-alpha (TNF-alpha) from human alveolar macrophages and monocytes as well as mouse peritoneal macrophages, where 1 micrograms of M. faeni elicited the secretion of approximately 100 U of TNF alpha from 2 x 10(5) macrophages, and 100 micrograms stimulated the release of approximately 1,000 U of bioactive TNF-alpha. One particle of whole M. faeni per cell was sufficient to induce copious release of TNF-alpha from macrophages or monocytes (100 U of bioactive TNF-alpha; 1,000 pg/ml of antigenic TNF-alpha as seen by radioimmunoassay). Both IL-1 and TNF-alpha productions stimulated by M. faeni were not abrogated by inclusion of polymyxin B. We propose that the direct stimulation of cytokines by M. faeni or antigens thereof may play an important role in HP. PMID- 1892651 TI - Replication origins, factors and attachment sites. AB - The initiation of eukaryotic DNA synthesis occurs at specific sites determined by both cis- and trans-acting elements. Here I review advances in the characterization of yeast origins, origin-binding proteins and the relationship of DNA replication to nuclear substructure in yeast. PMID- 1892652 TI - Origins of replication: timing and chromosomal position. AB - Several new methods have been used to localize replication initiation sites in mammalian chromosomes. The results of these studies argue strongly for the presence of defined sequence elements that function much like the origins in the genomes of simple microorganisms. However, relatively disparate results from in vivo and in vitro studies suggest that initiation reactions in mammalian chromosomes may have unique features, possibly related to a more complicated chromosomal architecture. PMID- 1892653 TI - DNA repair and the role of chromatin structure. PMID- 1892654 TI - Histone structure and function. AB - The past year has seen major advances in our understanding of histone and nucleosome structure and function. Direct DNA mapping and thermodynamic experiments have finally provided conclusive evidence that the histones impose an altered helical pitch on the DNA as it is wrapped on the surface of the core histone octamer. Further, it is now clear that lysine acetylation in the amino terminal domains of histones H3 and H4 can alter the topology of the DNA in chromatin and probably influence its higher-order folding. Genetic experiments reported in the past year have provided a wealth of new information on histone structure and function, including the identification of the peptide domain of histone H4 that is necessary for permanent gene repression, the confirmation that nucleosome structure is critical for centromere function, and evidence that histone acetylation plays a significant role in chromosome dynamics. PMID- 1892655 TI - Cytosine methylation in gene-silencing mechanisms. AB - Cytosine methylation is associated with gene-silencing mechanisms in a number of eukaryotic organisms. Recent studies directed at the involvement of methylation in promoter inactivation, X-chromosome and duplicate sequence inactivation and in chromatin structure changes, are presented. PMID- 1892656 TI - Telomeres. AB - Telomeres are essential for chromosome stability and replication. Maintaining a balance between telomere shortening and lengthening is essential for cell viability. Recent work on telomeres from yeast, Drosophila and mammals, and on telomerase has provided insight into the mechanisms of both the shortening and lengthening processes. PMID- 1892657 TI - Mechanistic advances in eukaryotic gene activation. PMID- 1892658 TI - RNA polymerase III transcription. AB - Remarkable progress has been made in defining the functional significance of the protein-DNA interactions involved in transcription complex formation on yeast tRNA and 5S RNA genes. This new information leads to a re-evaluation of how the class III gene transcription machinery operates. PMID- 1892660 TI - Nucleus and gene expression. PMID- 1892659 TI - Nuclear oncogenes. AB - Ample evidence has accumulated in recent years to establish that most, if not all, nuclear proto-oncogenes are in fact sequence-specific DNA-binding proteins that modulate gene expression. Their synthesis or activity is modulated by extracellular signals or by cross talk between different classes of transcription factors. PMID- 1892661 TI - The Cardiothoracic Society (Pete's Club) 1959 to 1989. AB - Pete's Club was founded in 1959 by a group of young thoracic surgeons from the United Kingdom at a time when new operative techniques for the surgery of the lung and the oesophagus, together with the feasibility of open-heart surgery following the development of the artificial heart-lung machine, allowed a rapid expansion of this branch of surgery. Unrecognised problems were frequently encountered and therefore the constitution of the Club declared that the scientific business should be the discussion of mistakes and errors of judgement. No member was allowed to report a case which reflected credit on himself. In 1969 members were elected from the European continent and in 1981/1982 from Canada, the United States of America, Australia and New Zealand. The development of the Club is described, together with an assessment of its contribution to the present day safety of cardio-thoracic surgery. PMID- 1892662 TI - Surgery for primary, invasive and metastatic malignancy of the chest wall. AB - Forty-four patients with primary (n = 6), invasive (n = 19) and metastatic (n = 21) chest tumours underwent complete resection between 1986 and 1989 in a total of 46 consecutive procedures. Nineteen patients were female and 25 male; 2 patients, 1 male, 1 female, had second operations. The underlying disease was bronchial carcinoma in 17 (14 male), mesenchymal tumours in 17, metastatic breast cancer in 7 and miscellaneous in 5. The chest wall resection included up to 6 ribs. The manubrium was resected in 2 patients, the corpus sterni in 5. Pulmonary resection was performed in 36 cases in an en-bloc fashion. Other concomitant resections included the pericardium, diaphragm or transverse process of the vertebrae. Amputation of the right arm was necessary in two cases. Reconstruction of the thoracic cage was accomplished with PTFE soft tissue patches in 7, methyl methacrylate implants in 2, Marlex mesh in 1 and Vicryl net in 6 cases. In the majority of cases, particularly in dorso-apical and posterior defects, no substitutes were used. A variety of plastic procedures including the use of omentum, musculo- and fasciocutaneous flaps was employed for the reconstruction of the integument. There was no operative mortality. Fourteen patients died after surviving 2-25 months. Serious infection occurred in 1 patient and minor delay of healing in 2. Good palliation can be achieved at low risk. The effect on long term survival remains uncertain, depending on the basic pathology. PMID- 1892663 TI - Validation of the TNM classification (4th edn) for lung cancer: first results of a prospective study of 1086 patients with surgical treatment. AB - For the purpose of testing the validity of the new TNM classification (fourth edition) for lung cancer, data from 1086 patients with surgical treatment were analysed prospectively. Several items were examined: (1) the agreement between clinical (TNM) and pathologically confirmed classification (pTNM); (2) the value of the various diagnostic tests in estimating the pathologically confirmed classification; (3) the influence of the TNM definitions on separating distinct prognostic groups. With regard to the primary tumour (T), clinical and pathological classification were identical in 64% of the cases. With regard to lymph node involvement (N), the agreement was 48%, for distant metastasis 90% and for the staging 55%. As for the primary tumour (T), the accuracy of radiography (59%) was nearly identical with that of computed tomography (58%). Both these diagnostic techniques were less precise in determining the extent of lymph node involvement (computed tomography 50% correct assessments, radiography 43%). The statistically significant differences in the prognoses for the various pT, pN and pM categories as well as for the pathological stages and the categories of the new R classification could be confirmed. The new 1987 TNM definitions for lung cancer make possible international conformity; the classification is also practically useful and the prognostic relevance improved. The new classifications thus provide a more reliable basis for establishing guidelines for individual oncological therapy strategies and for the exchange of information between different centres on the progress made in diagnosis and therapy of lung cancer. PMID- 1892664 TI - Post traumatic tracheobronchial lesions. A follow-up study of 47 cases. AB - This report concerns 47 ruptures of the tracheo-bronchial tree from the tracheal origin to the division of the lobar bronchi (trachea in 30 patients, main bronchus in 11, intermediate or lobar bronchus in 6). The disruption was circumferential in 24 cases and non-circumferential in 23. Injuries resulted from crush or blunt trauma in 35 cases, from seat belt or rope strangulation in 8 cases and in 4 cases, lesions were discovered following the tracheal intubation. The main symptoms were cervico-mediastinal emphysema (39), pneumothorax (31), acute dyspnea (28) and hemoptysis (11). The diagnosis was always confirmed endoscopically. In 8 patients, management of the lesions was delayed for more than 1 week due to misdiagnosis or severe associated injuries. Thirty-eight patients underwent tracheal or bronchial surgical repair associated in 13 cases with a temporary stenting, 4 patients underwent partial or total lung resection, 2 were managed by laser therapy and the 5 others received only medical care and endoscopic survey. Four patients died (8.5%), 2 from bleeding in the bronchial tree from a pulmonary artery tear, 1 from hypertensive pneumothorax under respiratory support and the last from mediastinitis due to delayed diagnosis of an associated oesophageal wound. All 43 other survived in spite of some very critical situations. This experience confirms that technical problems of surgical repair are nowadays overcome and that prognosis of tracheobronchial ruptures mainly depends on the initial control of respiratory failure and complications. Avoiding lethal anoxia or endobronchial damage in the emergency period before referring the patient to the surgeon is essential. PMID- 1892665 TI - Cardiac surgery and distribution of the leukocyte L1 protein-calprotectin. AB - Activated polymorphonuclear leukocytes (PMN) secrete lysosomal enzymes, eicosanoids and toxic oxygen metabolites. In cardiac surgery patients, we measured arterial plasma levels of PMN and L1 (calprotectin), a prominent granulocyte protein, during cardiopulmonary bypass (CPB). The myocardial arterio venous gradients were evaluated during reperfusion after cold cardioplegic arrest (n = 10). The arterial plasma concentration of L1 increased during CPB from 344 +/- 71 micrograms/l (mean +/- SD) preoperatively to 5221 +/- 1267 micrograms/l at the end of CPB (P less than 0.001). Simultaneously, the number of circulating PMN also increased (from 4.4 +/- 0.4 x 10(9)/l to 9.1 +/- 1.2 x 10(9)/l (P less than 0.05)). There was a positive correlation between the mean number of circulating PMN and the plasma level of L1 at all sampling times during CPB (r = 0.93, P less than 0.05). A coronary sequestration of both L1 (P less than 0.006) and PMN (P less than 0.002) was found after 5 min reperfusion. This was not present at 15 and 30 min reperfusion. The coronary entrapment of L1 and PMN did not covary significantly, and was unrelated to both the time of cardioplegic arrest and the arterial levels of L1 and PMN. In conclusion, the increased plasma concentrations of PMN and L1 during CPB and the coronary sequestration of both PMN and L1 may be factors in the pathogenesis of reperfusion injury of the myocardium. PMID- 1892666 TI - Anomalous origin of the left coronary artery from the pulmonary artery: repair by aortic reimplantation. AB - From 1980 to 1990, 12 patients (mean age 2.5 years, range 5 months to 9 years) with anomalous origin of the left coronary artery from the pulmonary artery were treated surgically. Five infants were operated upon in the first year of life because of persistent symptoms of congestive heart failure. In all cases, a two coronary system was constructed by direct aortic reimplantation of the anomalous vessel with no deaths early or late over a follow-up period of up to 10 years. The technique of reimplantation was facilitated by transection of the main pulmonary artery. One patient with severe mitral regurgitation underwent, in addition, a mitral annuloplasty. A pulmonary valvotomy was performed in another patient with associated pulmonary stenosis. Three patients are receiving medication. The reimplanted anomalous left coronary artery was patent in each reevaluated patient (10/12). Left ventricular function improved considerably in all cases. Patients with symptoms should undergo repair soon after diagnosis. Direct aortic reimplantation should be technically feasible in even the smallest infant. Operative mortality is related to preoperative conditions and severity of ischemic damage of the myocardium. PMID- 1892667 TI - Aortic valve replacement in patients over 80 years of age: a comparative standard for balloon valvuloplasty. AB - Elderly patients who develop symptomatic aortic valvular malfunction have a grave prognosis. Until recently they have not been seriously considered for active treatment, such as valvular surgery or balloon valvuloplasty. Between January 1972 and July 1989, 88 patients over the age of 80 years underwent aortic valve replacement and have been prospectively followed for a total of 185 patient years. The majority were in New York Heart Association functional class III (48%) or IV (48%) preoperatively. Valvular pathology was pure aortic stenosis in 81%, regurgitation alone in 6%, and mixed lesions in 13% of the cases. Before 1982 the majority of patients received mechanical valves, whereas tissue valves have predominated since then (76% of total). Forty-three percent of the patients had concomitant coronary artery bypass grafting. The overall operative mortality was 16%. Emergency surgery, isolated aortic valve replacement, advanced preoperative functional class, and female gender carried a statistically higher operative mortality. The overall actuarial survival (standard error) at 5 years was 64(7)%. Survival was significantly higher at 5 years for concomitant coronary bypass grafting than for isolated aortic valve replacement, 70 (11)% versus 59(8%), and for males compared to females, 73(9)% versus 55(9)%. The 5-year event-free rates for valve-related death and valve re-replacement were 97(2)% and 93(5)%, respectively. These data provide a firm basis for aortic valve replacement as the standard form of treatment in patients over 80. PMID- 1892668 TI - Surgery for critical congenital aortic stenosis during the first three months of life. AB - Open commissurotomy for critical aortic stenosis has been performed in a consecutive series of 28 neonates and infants below 3 months of age (average age 1 month) including 5 patients with severe organic mitral valve disease in need of concomitant correction. In the majority of cases, aortic stenosis was due not only to fused commissures but also to excessive immature valve tissue protruding into the valve area. Therefore a technique of extended commissurotomy has been adopted resecting such nodules responsible for a secondary level stenosis. All operations were done under deep hypothermia (17 degrees C), circulatory arrest (33 +/- 11 min) and cardioplegia using the Bretschneider solution (35-50 ml/kg). Hospital mortality was 18% (5) including 1 infant dying at 2 months of thrombosed mitral prosthesis inserted at a secondary operation. Severe organic mitral valve disease proved to be the only significant risk factor for early mortality. During the follow-up period of up to 10 years (average 5 years), 1 child with a hypoplastic left heart died and 2 children had to undergo reoperation for residual and recurrent stenosis, respectively. Actuarial survival for the present series is 78% at 10 years while reoperation free survival for the aortic valve is 64%. It is concluded that careful and if necessary extended open commissurotomy still represents the method of choice in this age group. Alternative methods such as transventricular or percutaneous dilatation did not show a lower risk until now and long-term results are not convincing as yet. PMID- 1892669 TI - An unusual presentation of systemic lupus erythematosus. AB - A case of right hemiparesis in a 22-year-old, caucasian male is presented. Echocardiography and an indirect left ventriculogram revealed a mass in the left ventricle which was eventually removed at surgery. Histology of the ventricular wall revealed thrombus superimposed on a full thickness myocardial infarction with florid intimal proliferation of small arteries. This histological picture suggested a diagnosis of systemic lupus erythematosus. Serum immunology revealed raised antibody titres in keeping with systemic lupus erythematosus. This is an unusual presentation where the only manifestation of disease was hemiparesis secondary to an embolic episode, from thrombus in the left ventricle subsequent to a small localised myocardial infarct. PMID- 1892670 TI - Familial atrial myxoma. AB - Familial and biatrial myxomas of the heart have rarely been described. We describe a familial atrial myxoma involving a parent with biatrial and a child with a left atrial myxoma. Atrial myxomas were diagnosed preoperatively by echocardiography and successfully removed at operation. Echocardiography can be used in the diagnosis of cardiac myxoma, detection of its possible recurrence and for screening other members of the family. PMID- 1892671 TI - Calcified constrictive pericarditis. Ultrasonic debridement. AB - A case of complete debridement of a calcified pericardium in a patient with constrictive pericarditis is reported. The use of an ultrasonic surgical aspirator facilitated disintegration of calcium without damaging the adherent epicardium and myocardium. PMID- 1892672 TI - Soft tissue sarcomas in Iceland 1955-1988. Analysis of survival and prognostic factors. AB - From 1955 to 1988 a total of 129 cases (69 males and 60 females) of soft tissue sarcomas were diagnosed in Iceland, four at autopsy. The median age was 55 years (0-91). All the cases have been reviewed clinically and histopathologically and graded on both a three- and a four-point scale. The average age-standardized incidence was 1.8/100,000 for males and 1.6 for females. The tumour was most often localized in the thigh and retroperitoneal space. The most common histologic subtypes were malignant fibrous histiocytoma (22.5%), liposarcoma (18.6%) and leiomyosarcoma (16.3%). The 5- and 10-year survival rates (n = 125) were 38% and 29% respectively. Cox's multivariate analysis was performed on the following prognostic factors: age, sex, tumour localization, histopathologic subtype, tumour size, malignancy grade and year of diagnosis. The strongest prognostic factor was malignancy grade (IV vs I; p less than 0.001 and RR = 5.35 and III vs I; p = 0.017 and RR = 2.01) followed by tumour size (pT2 vs pT1; p less than 0.001 and RR = 3.09 and pT3 vs pT1; p = 0.002 and RR = 3.40) and year of diagnosis (p = 0.003 and RR = 0.96; corresponding to a 54% reduction in mortality risk during a 20-year period). PMID- 1892673 TI - Risk factors for female breast cancer. A hospital-based case-control study in Madras, India. AB - Five hundred and thirty-one histologically confirmed breast carcinoma cases examined from 1983 to 1986 inclusive at the Cancer Institute (WIA), Madras, India, were matched for age, socioeconomic class and menopausal status with an equal number of controls. Cancer patients without diseases in breast, gynaecological organs or endocrine glands were used as controls. Risk factors for breast cancer were analyzed separately in the premenopausal and the postmenopausal groups. In neither group was there significant association between age at menarche and breast cancer risk. Single women had higher risk than married women. Nulliparity was found to be a risk factor in premenopausal women only. The relative risk increased with age at marriage and age at first birth. A three-fold risk was noted in both pre- and postmenopausal groups when the interval between age at first birth and menarche was more than 12 years and also in women who attained menopause between the age of 44-49. PMID- 1892674 TI - Association between testicular cancer and spina bifida occulta. AB - Data are reported suggesting a high incidence of spina bifida occulta among testicular cancer patients. The relevance of a diagnosis of spina bifida occulta as a risk factor for testicular cancer is discussed, also considering the background information available on a common genetic origin for some urogenital malignancies which are often associated with different types of malformations. PMID- 1892675 TI - Prognostic factors associated with survival after breast cancer recurrence. AB - Factors associated with disease-free interval after the primary treatment and survival after a recurrence of breast cancer were studied in 331 female breast cancer patients treated in 1976-1980. Within five years after the primary treatment, recurrence occurred in 131 patients. The observation time of these patients after recurrence was from few weeks to twelve years. Twenty-nine patients were alive at the end of the follow-up. The average disease-free time was 2 years. The clinical stage of the disease in this material was not significantly associated with the disease-free interval. The median survival time after recurrence was 2.7 years when only breast cancer related deaths were included. Survival was significantly better for patients with primarily stage I disease than for patients with primarily stage II-IV disease. The size of the primary tumour was not significantly associated with survival after recurrence. The patients with loco-regional recurrence survived almost significantly better than those with distant recurrence. The disease-free time correlated positively with survival after a recurrence. The present study confirms the view that breast cancer includes several subgroups with a different type of clinical course. PMID- 1892676 TI - Hodgkin's disease in northern Sweden 1971-1981. I. A histopathological reevaluation of 223 cases. AB - A histopathological reexamination was made of diagnostic material in 223 patients with Hodgkin's disease (HD) collected between 1971 and 1981. The diagnosis of HD was considered to be incorrect in 90 cases (40%). Change of diagnosis to non Hodgkin's lymphoma was made in 56 cases, of which 23 were high-grade and 26 were low-grade lymphomas (7 not determined), and to angioimmunoblastic lymphadenopathy in 10 cases. These discrepancies were considered to be due mainly to progress in the understanding and classification of malignant lymphomas, which stresses the importance of review of histologic material in retrospective studies on Hodgkin's disease. PMID- 1892677 TI - Hodgkin's disease in northern Sweden 1971-1981. II. A retrospective analysis of prognostic factors. AB - Factors relevant for prognosis were retrospectively studied in a series of 133 morphologically reviewed patients with Hodgkin's disease collected between 1971 and 1981. For the whole material complete remission rate was 74% and 5-year survival was 62%. These seemingly rather poor results could be explained by a high mean age (48 years) in this relatively unselected material, in combination with a very unfavourable outcome for the elderly patients. In a multivariate analysis of prognostic factors age of the patient turned out to be the only independent factor with a significant bearing on the prognosis. PMID- 1892678 TI - Treatment of metastatic carcinoid tumors and the carcinoid syndrome with recombinant interferon alpha. AB - Fourteen patients with metastatic carcinoid tumors were treated with recombinant interferon alpha-2b at a dosage of 3-4 x 10(6) IU s.c. daily or every second day. No objective tumor regression was observed. Six out of 8 patients with carcinoids of the ileum and the caecum showed stable disease lasting for a median of 25 months (range 4-57). In 3 out of 6 patients with carcinoids of rectum, lung and of unknown primary site, stable disease was observed lasting for 2-7 months. The remaining patients had progressive disease. Six out of 9 evaluable patients had a more than 50% reduction of urinary 24 h 5-hydroxyindoleacetic acid excretion lasting for a median of 4 months (range 2-11). Decrease of flushing was noticed in 3 out of 6 evaluable patients and decrease of diarrhea in 5 out of 9 evaluable patients. In 4 patients dose reduction was necessary due to confusion and fatigue. PMID- 1892679 TI - Leukocyte interferon in the treatment of chronic myelogenous leukemia in second chronic phase. AB - Four patients with Philadelphia chromosome positive CML were treated with 18-42 x 10(6) IU of purified natural leukocyte IFN-alpha per week, after high-dose chemotherapy for blast phase and attainment of 2nd chronic phase. The second blast phase occurred within 3 months in 3 patients, but one patient is still in second chronic phase after 22 months of treatment. Treatment consisted of interferon only during the first year, and interferon in combination with hydroxyurea during the second year. During the second year suppression of the Philadelphia chromosome was seen in one patient, with 20% Philadelphia negative bone marrow metaphases. The toxicity of purified natural leukocyte IFN-alpha was similar to the toxicity of recombinant IFN-alpha. Antibodies to IFN-alpha were not detected in any patient. PMID- 1892680 TI - Antiemetic regimens in outpatients receiving cisplatin and non-cisplatin chemotherapy. A randomized trial comparing high-dose metoclopramide plus methylprednisolone with and without lorazepam. AB - Results of a randomized trial on antiemesis for cisplatin (CDDP) and non-CDDP chemotherapy-induced vomiting are reported. One hundred and sixty-three outpatients received 282 chemotherapy courses (141 with CDDP and 141 without CDDP). Patients were randomly assigned to receive either high-dose metoclopramide plus methylprednisolone (arm A) or the same drugs plus lorazepam (arm B). In both arms a high protection rate for vomiting was obtained, on the whole without statistically significant differences. Patients who received lorazepam had, however, significantly fewer nausea episodes during first day post-chemotherapy (p less than 0.05). Arm B was also superior in anxiety control during the first day of chemotherapy (p less than 0.01). Both regimens were significantly more effective in patients who had not been given chemotherapy previously (p less than 0.01). No differences in antiemetic protection were found between CDDP and non CDDP courses. No significant differences were found in premonitory vomiting control between the two arms of the trial. Toxicity was very mild with both regimens, although sedation was significantly higher in arm B (p less than 0.001). We conclude that high-dose metoclopramide plus methylprednisolone is a highly effective combination for chemotherapy-induced nausea and vomiting, and that it is quite suitable for outpatient use. Lorazepam did not significantly increase the antiemetic potency of the combination, nor did it improve premonitory vomiting control, although it gave a better control of acute nausea and anxiety. PMID- 1892681 TI - Squamous cell carcinoma of the tonsillar region. A retrospective analysis of treatment results. AB - Seventy-five patients treated for squamous cell carcinoma of the tonsillar region during 1958-1982 were reviewed retrospectively. Of the 75 patients, 30 received combined treatment with surgery and postoperative radiotherapy, and 45 radical radiotherapy alone. The 5-year survival rate for the entire patient series was 39%, the corresponding figure was 53% for the patients treated with combined therapy and 29% for the patients with radical radiotherapy. The radical radiotherapy group included more patients with advanced stage of the disease (stage III 27% and stage IV 66%) than the combined therapy group (47% and 23% respectively). Thirty-four patients (45%) died from uncontrolled disease. PMID- 1892682 TI - Additional information from quantitative 24-hour 99mTc-MDP bone scintigraphy in patients with prostatic carcinoma. AB - Quantitative bone scintigraphy was performed at 4 and 24 h after injection of 99mTc-MDP. The lower thoracic and all the lumbar vertebrae were recorded in 37 patients with prostatic carcinoma before orchiectomy as well as two weeks, two and six months postoperatively. Fourteen patients had normal bone scintigrams. By means of the measured variation in the count rate between normal vertebrae, the criterion for a vertebra to be considered as abnormal was determined using the 4 h-uptake values. For patients with normal scintigrams the count rate at 24 h was below the 4 h level and the mean 24 h/4 h ratio was determined to be 0.85 +/- 0.09 (1 SD). Normal vertebrae in patients with skeletal metastases had only slightly lower count rate values at 24 h than at 4 h. Abnormal vertebrae showed a higher count rate at 24 h, especially two weeks postoperatively, while a tendency towards lower values than at 4 h was seen after 6 months. If the 24 h/4 h ratio is used as an extra criterion to the count rate at 4 h, the vertebrae will be more accurately defined as normal or abnormal. PMID- 1892683 TI - Hydralazine-induced changes in tissue perfusion and radiation response in a C3H mammary carcinoma and mouse normal tissues. AB - Hydralazine has been reported to reduce blood perfusion in tumours, thereby increasing hypoxia and subsequently enhancing tumour sensitivity to certain drugs and hyperthermia. We have investigated the ability of hydralazine to induce such changes in a C3H mouse mammary carcinoma and various normal tissues. In tumours, hydralazine (5 mg/kg; i.v.) modified the radiation response, measured by a local tumour control assay, producing an effect equivalent to that seen in tumours made fully hypoxic by clamping. This effect was time-dependent and correlated with the decrease in tissue perfusion estimated by the 86-RbCl extraction procedure. Similar effects were seen in normal skin, although the changes were less dramatic and of a shorter duration. Hydralazine also reduced 86-RbCl uptake in liver, kidney, gut and spleen, but not in bladder, muscle and lung, suggesting that it may have the potential to increase the sensitivity of some normal tissues to hypoxic cell cytotoxins. PMID- 1892684 TI - Lung cancer after treatment of Hodgkin's disease--a case report. PMID- 1892685 TI - Normal anatomy of the infrahyoid neck: an overview. PMID- 1892686 TI - The visceral space: the unique infrahyoid space. PMID- 1892687 TI - The carotid space of the infrahyoid neck. PMID- 1892688 TI - The normal and diseased infrahyoid retropharyngeal, danger, and prevertebral spaces. PMID- 1892689 TI - The anterior and posterior cervical spaces. PMID- 1892690 TI - Multispatial and transpatial diseases of the extracranial head and neck. PMID- 1892691 TI - Sonographic manifestations of medical renal disease. AB - Ultrasound is usually the first imaging procedure used to evaluate the kidneys in a patient presenting with renal failure. It can allow the physician to make a specific diagnosis of bilateral hydronephrosis as the cause of the renal failure and irreversible end-stage renal disease when bilaterally small echogenic kidneys are seen. In the early stages of medical renal disease, the kidneys may appear normal. As parenchymal diseases progress, changes in the echo architecture of the renal parenchyma take place. These changes, however, are nonspecific and ultrasound-guided biopsy may be necessary to determine the exact histological cause of the patient's renal failure. PMID- 1892692 TI - Examination of native kidneys with duplex Doppler ultrasound. PMID- 1892693 TI - Renal transplant ultrasound: imaging and Doppler. PMID- 1892694 TI - Upper urinary tract infection: the current role of CT, ultrasound, and MRI. AB - This article reviewed some of the fundamental concepts in renal inflammatory disease. The difficulties in present terminology were reviewed and our approach discussed. The pathological underpinning of the acute-subacute infections were contrasted with those seen in the granulomatous diseases. The importance of CT in separating emphysematous pyelonephritis from emphysematous pyelitis and perinephric emphysema was stressed. Although ultrasound has been used in the past and is still of value in select situations, we prefer CT for assessment of renal infection. CT examinations show whether the disease is focal or diffuse, whether air is present, whether there is perinephric or pararenal extension, whether an abscess is present, and when the ideal time is for intervention. In severe renal infection in the adult, CT has shown the development of renal scars, perinephric extension, and the spontaneous drainage of Staphylococcus abscesses into nearby calyces. PMID- 1892695 TI - Renal cystic disease. PMID- 1892696 TI - Nutrition research from respiration and vitamins to cholesterol and atherosclerosis. PMID- 1892697 TI - The interactions between copper, molybdenum, and sulphur in ruminant nutrition. PMID- 1892698 TI - Current issues in fructose metabolism. AB - The ingestion of fructose, particularly in refined form, has significantly increased in the North American diet over the last two decades. The unique way in which fructose is metabolized has given rise to much research examining whether fructose is advantageous in appetite control, exercise endurance, and disease states such as diabetes. Overall, there is very little evidence that modest amounts of fructose have detrimental effects on carbohydrate and lipid metabolism in nondiabetic or NIDDM subjects or that its use is particularly advantageous compared to that of other sugars. However, fructose can cause insulin and triglyceride levels to rise dramatically, and hence be potentially harmful, in a subgroup of NIDDM subjects who have concomitant pronounced hypertriglyceridemia. Large doses of fructose should also be avoided by subjects with gout because of the hyperuricemia which may result. No evidence exists that fructose has any clear advantages over glucose in regard to exercise endurance. Similarly there is no conclusive evidence that physiologic amounts of dietary fructose exacerbate copper deficiency or aid in weight control. PMID- 1892699 TI - Lipoprotein lipase. PMID- 1892700 TI - Comparative nutrition of cats and dogs. PMID- 1892701 TI - Dietary copper: cholesterol and lipoprotein metabolism. PMID- 1892702 TI - Glutamine: a key substrate for the splanchnic bed. PMID- 1892703 TI - Fluorides and osteoporosis. AB - Sodium fluoride has clearly been shown to have pronounced effects on the skeleton, probably more than any other currently available therapeutic agent. Unfortunately, these effects appear to be both beneficial and potentially toxic at the same time. A more clear understanding is needed of the basic mechanisms whereby these effects (both beneficial and detrimental) are exerted. When such data are forthcoming, it may be possible to modify the therapeutic use of fluoride in osteoporosis and other brittle bone diseases such that the beneficial effects outweigh the toxic effects much more completely than is currently the case. Until such time, and despite thirty years of meaningful clinical investigation, we must conclude that sodium fluoride has no role in clinical medicine outside the confines of properly conducted clinical research studies. PMID- 1892704 TI - Animal models of obesity: genetic aspects. AB - Among the candidate genes that have been reviewed herein, adipsin, calcitonin, cholecystokin, Gi alpha and Gs subunits of G proteins, insulin I and II, and lipoprotein lipase have all been mapped to specific chromosomes in mouse or rat or both. In none of these cases is the chromosomal location syntenic with murine obesity genes db (on chromosome 4), or ob (on chromosome 6). Thus, all of these genes that code for metabolic modulators that are altered in obese animals but not in lean animals can be ruled out as possible loci of the primary genetic defect, at least for the murine models of obesity. In the case of neuropeptide Y, growth hormone, glucose transporter GLUT-4, the insulin receptor, and glyceraldehyde-3-phosphate dehydrogenase, chromosomal mapping has not yet been reported. However, in each of these cases, the evidence available strongly argues against any one of these physiologic modulators as the likely site of the primary defect for any one of the obesity mutations. Rather, in all of these cases, regardless of whether or not the gene has been mapped, the evidence suggests that posttranscriptional and/or post-translational processes are involved in bringing about the specific alterations in level or activity of the protein product that is seen in the obese animal. Often hormonal regulation is invoked as a possible explanation for the changes observed in gene expression. The hormones most commonly identified as having a mediating effect on the particular metabolic pathways involved are insulin and/or the adrenal glucocorticoids. Since in each of the obese mutants, circulating amounts of these hormones are elevated, severely so in the case of insulin, it would not be surprising to find that they influence the levels and activities of many protein products involved in a variety of central nervous system and peripheral metabolic pathways. Glucocorticoids are known to exert direct effects on gene expression; however, with respect to adipsin gene expression, a direct effect has not been found. Furthermore, insulin itself has been considered as a candidate for the genetic lesion in these animals and has been ruled out by chromosomal localization. Thus, while it may certainly prove to be the case that both insulin and glucocorticoids affect these systems in some way, their effects appear to be indirect. The work by Platt and colleagues in transgenic mice provides the first evidence of signal transduction between an obese mutant allele and the promoter sequence for a gene that shows significantly altered expression in the obese animal.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1892705 TI - Human energy metabolism: what have we learned from the doubly labeled water method? PMID- 1892706 TI - Should there be intervention to alter serum lipids in children? PMID- 1892707 TI - Biosynthesis of prostaglandins. PMID- 1892708 TI - The effects of glyceride structure on absorption and metabolism. AB - The subtle effects of the stereochemistry of acyl glycerols are apparent from the cited studies. It is not adequate to simply measure the fatty acid composition of dietary lipids or chylomicrons generated from them. To understand the importance of stereospecific acyl glycerols, simplification of the systems is necessary because of the incredible diversity found among dietary triacylglycerols. By feeding simple analogues corresponding to major triacylglycerols found in oils and fats it should be possible to determine the absorption, uptake into the mucosa, resynthesis into chylomicrons, and the stereospecificity that remains. Hydrolysis and uptake of these defined chylomicron triacylglycerols into adipose tissue or muscle could be followed and stereospecificity again determined in depot fats. Finally, the composition of the remnants, particularly the core and surface, and of the bound apoproteins needs to be related to their plasma residence time, hepatic removal, and deposition in nonhepatic tissues such as spleen, bone marrow, and arterial intima. Since increased serum cholesterol and atherogenicity in animals have been related to different dietary fats, some of the effects noted here, that is the retention of certain kinds of remnants in plasma, may lead to increased serum cholesterol and atherogenesis. We must study the metabolism of a few key stereospecific triacylglycerols in more detail to increase our understanding of their effects on hypercholesterolemia and atherogenesis. PMID- 1892709 TI - Phosphorus magnetic resonance spectroscopy in nutritional research. AB - In conclusion, muscle and liver 31P MRS can be used to assess energy state in various nutritional conditions and to follow different metabolic changes induced by modification of substrate availability. 31P MRS studies of humans and animals suggest that fasting and low caloric intake reduce the oxidative metabolism "efficiency" of muscle during exercise and produce a better bioenergetic state at rest. Liver studies during fasting also indicate a lower energy state. Acute supplements of substrate to working muscle that is affected by a metabolic disease can improve its energy metabolism as observed by 31P MRS. Modification of diets in patients with a metabolic disease can also be followed by this technique, thereby aiding the clinical evaluation of therapies. The acute and chronic effects of alcohol, which reduce the energy metabolism of liver, are another example of nutritional problems studied by 31P MRS both in humans and animal models. A valuable aid in nutritional research, especially in humans, 31P MRS is noninvasive and can be repeated without harmful effects. PMID- 1892710 TI - Hepatic gluconeogenesis/glycolysis: regulation and structure/function relationships of substrate cycle enzymes. PMID- 1892711 TI - Nutritional consequences of vegetarianism. PMID- 1892712 TI - Cementless Gustilo-Kyle and BIAS total hip arthroplasty: 2- to 5-year results. AB - We conducted extensive radiographic and clinical examination of 58 cementless total hip arthroplasties. Forty BIAS femoral stems had heads made of Co-base F 75 alloy and 18 Gustilo-Kyle femoral stems had Ti6A14V alloy heads. The cross sectional geometry and location of the porous coating pads of the two stem types was identical, the BIAS component being slightly shorter. At the last follow-up, 27.8% of the Gustilo-Kyle femoral components and 2.5% of the BIAS femoral components were unstable. None of the acetabular components in the BIAS group as against 38.9% of the acetabular components in the Gustilo-Kyle group demonstrated wear of more than 1 mm. All unstable components which did not suffer intraoperative fracture had also acetabular wear of more than 1 mm. The only case with endosteal erosion was seen in a patient with an unstable implant displaying the most extensive wear. Nonparametric statistical analysis showed that the patients with Ti6A14V/polyethylene bearing surfaces had a statistically significantly higher extent of wear and a statistically significant higher incidence of femoral component loosening than patients with CrCoMo/polyethylene bearing surfaces. PMID- 1892713 TI - Aseptic loosening of straight- and curved-stem Muller femoral prostheses. AB - Out of 1099 Muller total hip prostheses with straight and curved stems consecutively implanted between 1980 and 1984, those performed in as homogeneous a group as possible of patients under the age of 70 years were selected for the present retrospective study. There were 158 straight femoral stems with cementless RM acetabular cups, 105 straight stems with cemented Muller acetabular cups, and 158 curved stems with cemented Muller acetabular cups, and their results over a mean follow-up period of 5.8 +/- 1.24 years were compared. Six (3.7%) curved and 5 (1.9%) straight-stem prostheses were exchanged due to aseptic loosening; 26 (16.3%) curved and 54 (20.1%) straight-stem prostheses were "at risk" or loose at the time of follow-up. Survival curves show a worse result for straight stems after 6 years; within a follow-up period of 6-8 years there was significantly more radiological loosening in straight stems than in curved. Loosening in straight stems is assumed to develop mainly as a physiological reaction to the presence of bone cement particles. PMID- 1892715 TI - Ultrasound diagnosis of pathology of the anterior and posterior cruciate ligaments of the knee joint. AB - We established a method of diagnosing pathologic conditions of both the anterior cruciate ligament (ACL) and the posterior cruciate ligament (PCL) by using ultrasound. Normal ACL and PCL were delineated as hyperechoic images on the screen in sagittal and transverse sections. On the other hand, no image of the ligament could be seen when the ligament was ruptured. We examined nine ACL and five PCL injuries by our method. This is a safe and an effective method of determining the rupture of ACL and PCL. PMID- 1892714 TI - Uncoated polyethylene RM acetabular component versus Muller cemented acetabular component. A 4- to 8-year follow-up study. AB - Comparable patient populations with 160 uncoated RM acetabular cups and 263 cemented Muller standard acetabular cups were submitted to survival-time analysis in a retrospective study with a mean follow-up of 5.3 years for the RM cup and 6.1 years for the Muller cup. After 7-8 years 12% of the RM cups and 4% of the Muller cups had been exchanged, 40% and 15% respectively were loose. The poor performance of the RM cups is ascribed to additional external polyethylene wear, which leads to the formation of granulomas and destroys the weight-bearing osseous structures. Similar granulomas also develop on the proximal stem and thus endanger the same. PMID- 1892716 TI - Giant cell tumour of the proximal end of the ulna. AB - An extremely rare case of giant cell tumour of the proximal end of the ulna, which was clinically aggressive but histologically benign, is reported in a 28 year-old man. The tumor was excised in en bloc but patient died 8 months after surgery. To the best of our knowledge, this is the first reported case from South East Asia and the second available in the English-language literature. It therefore warrants report. PMID- 1892717 TI - Traumatic bilateral anterior dislocation of the shoulders. A case report in a geriatric patient. PMID- 1892718 TI - Femoral intraosseous neurilemoma. AB - The neurilemoma (benign schwannoma) is a benign tumor which arises from the Schwann cells of the peripheral nerves. In an intraosseous localization it is a very rare lesion, only forty cases being reported in the literature, and only two of these with the tumor located in the femur. This paper reports on a patient with a large neurilemoma in the lower part of the left femur. PMID- 1892719 TI - Osteonecrosis of the femoral head during pregnancy. PMID- 1892720 TI - Tibia valga after fracture: documentation of mechanism. AB - Tibia valga following fracture in the proximal metaphysis of the tibia in children was previously attributed to various mechanisms. This case report offers an additional explanation based on bone scintigraphy 10 months after injury. Decreased radionuclide uptake at the lateral proximal tibial physis without evidence of increased uptake on the medial side suggests that a Salter type V injury to the lateral growth plate can occur in conjunction with a medial metaphyseal fracture, resulting in the development of tibia valga. PMID- 1892721 TI - Macrodystrophia lipomatosis in the foot. A case report and review of the literature. AB - A rare case of macrodystrophia lipomatosis in the foot is reported. The literature is reviewed and the different presentations of macrodactyly are discussed. PMID- 1892722 TI - Bilateral simultaneous rupture of the patellar tendon. Case report and review of the literature. AB - A case of bilateral simultaneous rupture of the patellar tendon due to apicitis patellae is presented. Clinical picture, diagnosis, pathogenesis and treatment are discussed. In addition, the literature on the subject is reviewed. PMID- 1892724 TI - [Autonomous thyroid nodule: relations between clinical symptomatology and goiter endemia]. AB - Sixty-three patients with autonomous thyroid nodule were studied, thirty-five from an endemic goiter area (EA) and twenty-eight from a non-endemic goiter area (NEA). Clinical history, physical examination, ultrasonography, thyroid hormone levels, and fine needle aspiration (FNA), were utilized to investigate whether or not iodine deficiency determined differences in the latency of progression to toxicity, the seriousness of illness and thyroid hormone levels. No significant difference was observed in the age of onset of nodularity, while the latency of progression to toxicity was significantly decreased in the EA (p less than 0.001). The ultrasonographic pattern did not show significant volume variations between the EA and NEA, but there was a slight prevalence of multinodular lesions in EA. No significant difference in serum thyroid hormone levels was found between the two areas in non toxic patients, while at the onset of hyperthyroidism higher levels of FT were observed in the EA than in the NEA. FNA showed a prevalence of colloid lesions in EA, while hyperplastic lesions prevail in the NEA. Forty-two patients underwent surgery: the extent of surgery was greater in patients from the EA. In conclusion, in iodine deficient areas earlier clinical thyrotoxicosis and a higher prevalence of hypoactive thyroid nodules were observed. Furthermore, in EA, the autonomous nodule in non toxic phase is more frequently associated with colloid lesions than hyperplastic lesions. PMID- 1892723 TI - [Occult pulmonary embolism in patients with proximal deep venous thrombosis]. AB - It is known that proximal deep-vein thrombosis (DVT) of the lower limbs is associated with a high risk of pulmonary embolism (PE). However, only a few patients presenting with clinically symptomatic DVT exhibit symptoms or signs suggestive of this complication. The prevalence of silent PE in these patients is unknown. In order to assess the true prevalence of PE in a patient population presenting with venographically proven proximal DVT but without symptoms of PE, a perfusion lung scan was performed in 100 consecutive patients at presentation. Fifty-nine patients (59%) had a high probability lung scan (segmental or larger perfusion defects in lung areas free from abnormalities as shown by conventional chest x-ray) at the initiation of heparin treatment. At repeated lung scanning, performed after 10 days of anticoagulant treatment, complete to partial improvement was observed in 41 of these patients (71%), whereas in 13 (23%) the picture was unchanged and in 3 (5.2%) it worsened. In 6 patients who developed symptoms suggestive of PE during the study period, a lung scan was immediately repeated and correct interpretation of the clinical manifestation was permitted by comparison with the initial scan. It is concluded that lung-scan--detected asymptomatic PE occurs frequently in patients with proximal DVT, and that the majority of these emboli resolve within 10 days of anticoagulant treatment. In order to manage correctly patients who develop clinical manifestations suggestive of PE while undergoing therapy for venous thrombosis, a baseline lung scan is strongly recommended in all patients with proven proximal DVT. PMID- 1892725 TI - [Immunogenetics: clinical and population aspects. HLA system: clinical correlations. I. (2d of 5 parts)]. PMID- 1892726 TI - [24-hour esophago-gastric pH-metry: clinical indications]. AB - Esophago-gastric 24 h pH-metry recording is a diagnostic technique that allows ambulatory monitoring of acid esophageal reflux during 24 h while the patient pursues his everyday activities. Prolonged pH recording allows evaluation of the correlation of esophageal or extraesophageal symptoms (i.e. arrhythmias, chest pain, asthma) with intraesophageal pH. It permits us to evaluate the effectiveness of antireflux therapy, to modify therapy, or change daily dosages. PMID- 1892727 TI - [Circadian rhythm of the heart rate and autonomic nervous system stimulation tests in patients with systemic lupus erythematosus]. AB - We studied 19 women (mean age 35 +/- 13 years) with systemic lupus erythematosus (SLE), in order to evaluate whether or not alterations in the circadian rhythm of heart rate (HR) occur in patients with pathologic responses to stimulation tests of the autonomic nervous system (ST-ANS). The duration of SLE was 5.3 +/- 5 years. None of the patients had clinical signs of cardiopathy or dysautonomy, nor were any of them taking drugs with known effects on the heart or ANS. Nine patients (47%, group A) had normal ST-ANS and 10 (53%, group B) had an abnormal response to at least 1 ST-ANS (5 to sympathetic ANS, 3 to parasympathetic and 2 to both ST-ANS). Age, duration of disease and therapy were not different between the 2 groups. All patients underwent 24-hour ambulatory ECG monitoring, and chronobiologic analysis of hourly HR was carried out by single and mean cosinor methods. A significant circadian rhythm was found both in the total sample (mesor 80 b/min, acrophase h 13:12; p less than 0.01), and, separately, in group A (mesor 82 b/min, acrophase h 13:11; p less than 0.01) and group B (mesor 78 b/min, acrophase h 13:12; p less than 0.01). No difference existed between the HR circadian rhythms of the 2 groups. Thus, our data show the possibility of ANS involvement in SLE patients without clinical signs of dysautonomy; the analysis of the HR circadian rhythm does not appear to be a sensitive method to identify early involvement of the ANS in these patients. PMID- 1892728 TI - [Diffuse idiopathic skeletal hyperostosis of the cervical spine in a patient with ankylosing spondylitis. Description of a personal case]. AB - Diffuse idiopathic skeletal hyperostosis (DISH) is a well-described disorder of middle-aged people, with a unique spinal pathology characterized by calcification and ossification of the antero-lateral aspect of at least four contiguous vertebral bodies, with the sparing of intervertebral spaces and sacroiliac joints. DISH has rarely been reported associated with ankylosing spondylitis (AS), a chronic inflammatory articular disease most commonly involving the spine and sacroiliac joints. A 63-year-old man with clinical and radiological findings of DISH with associated AS is described here. The authors conclude that these two diseases may, albeit rarely, coexist. PMID- 1892729 TI - [Unilateral exophthalmos caused by apparently unique localization of chronic sarcoidosis]. AB - Sarcoidosis is a chronic disease which can cause unilateral exophthalmos: occurrence in the orbit, though very rare, has already been described in some cases of chronic sarcoidosis. A case of its localization in the orbit with apparently no other evidence of sarcoid is reported in this communication. The recent evolution of clinical and instrumental methods of investigation has permitted us to make a more accurate and "sophisticated" diagnosis in this case with respect to others we have seen described in the literature. PMID- 1892730 TI - Thomas Hodgkin. PMID- 1892731 TI - Interplay between insulin signalling and protein kinase C. PMID- 1892732 TI - The ras superfamily of molecular switches. PMID- 1892733 TI - Interleukin-1 stimulation of arachidonic acid release from human synovial fibroblasts; blockade by inhibitors of protein kinases and protein synthesis. AB - Addition of IL-1 (interleukin-1) to human synovial fibroblasts radiolabelled with [3H]arachidonic acid caused a linear dose-dependent increase in arachidonic acid release and a transient rise in labelled diacylglycerol. Protein kinase C activators PMA 4-phorbol 12-myristate 13-acetate and DiC8 (1,2-dioctanoyl-sn glycerol) also increased arachidonic acid release, but the time course observed with PMA was different from that of IL-1. When cultures were treated with PMA for 16-24 h to down regulate protein kinase C, the ability of IL-1 to increase arachidonic acid release persisted to the same extent as in nontreated cultures. In contrast, PMA pretreatment prevented the eight-fold stimulation of arachidonic acid release in response to PMA observed in cultures not previously exposed to PMA. To examine the role of other kinases in IL-1 stimulated arachidonic acid release, cultures were treated with H-7 (1-(5-isoquinolinesulphonyl)-2 methylpiperazine dichloride), H-8 (N-[2-(methylamino) ethyl]-5 isoquinolinesulphonamide dichloride), HA1004 (N-(2-guanidoinoethyl)-5 isoquinolinesulphonamide hydrochloride), and staurosporine. IL-1 stimulation of arachidonic acid release was blocked by H-7, H-8 and staurosporine. H-7 was a more potent inhibitor than H-8, suggesting that cAMP dependent kinase did not mediate IL-1 action. Addition of H-7 at various times following IL-1 decreased IL 1 stimulated arachidonic acid release, suggesting that continued protein kinase activity was necessary for IL-1 action. Cycloheximide and actinomycin D inhibited the stimulation of arachidonic acid release by IL-1, PMA or DiC8. The addition of cycloheximide or actinomycin D 15-45 min after IL-1 also inhibited IL-1 stimulated arachidonic acid release, indicating that continued protein synthesis was required for IL-1 action. These results suggest that IL-1 stimulation of acylhydrolyase activity in human synovial cells occurs by a mechanism requiring continued protein synthesis and protein kinase activity and that neither protein kinase C nor cAMP dependent protein kinase is involved. PMID- 1892734 TI - Human neutrophils have a novel purinergic P2-type receptor linked to calcium mobilization. AB - Stimulation of suspensions of fura-2-loaded human neutrophils with ATP resulted in an elevation in cytosolic free calcium concentration ([Ca2+]i) from a basal value of 0.1 microM to a transient peak of 1 microM. The response is due to Ca2+ release from intracellular stores and influx of extracellular Ca2+. Release from intracellular stores is shown by the response in the absence of extracellular Ca2+. The greater and more maintained response in the presence of extracellular Ca2+ is indicative of stimulated Ca2+ entry and a stimulated influx pathway was confirmed by using Mn2+ as a surrogate for Ca2+. A variety of purinergic agonists were used to characterize the pharmacology of this [Ca2+]i response. Their rank order of potency was ATP greater than adenosine 5'-O-(3-thiotriphosphate) (ATP gamma S) greater than ADP much greater than 2-methylthioadenosine 5'-triphosphate (2Me-SATP), where ATP had an EC50 value of 3 microM and 2MeSATP had an EC50 value of 1000 microM. Adenosine 5'-O-(2-thiodiphosphate) (ADP beta S), adenylyl (alpha,beta-methylene)- diphosphonate (AMPCPP) and adenosine were inactive at 1 mM. These results suggest that neutrophils have a novel type of purinergic P2 receptor that is neither P2x nor P2y. PMID- 1892735 TI - Defective protein kinase C-mediated actions in cystic fibrosis neutrophils. AB - Neutrophils from cystic fibrosis (CF) patients have been shown previously to be defective in their response (beta-glucuronidase exocytosis, NADPH oxidase activation) to the chemotactic peptide FMLP. In this work, we attempted to identify the defective step in this response. We showed that stimulated CF and control neutrophils do not differ in the formation of inositol phosphates. On the other hand, direct stimulation of protein kinase C with phorbol myristate acetate (PMA) revealed a subnormal stimulation of beta-glucuronidase exocytosis in CF neutrophils. Furthermore, retroinhibition exerted by PMA-activated protein kinase C on stimulated inositol phosphates or on beta-glucuronidase exocytosis was marginal or absent in CF neutrophils, whereas it was significant in the case of control neutrophils. Our observations suggest that the CFTR gene is expressed in neutrophils and is involved in protein kinase C-mediated actions. PMID- 1892736 TI - International Union of Microbiological Societies (IUMS). International Committee on Food Microbiology and Hygiene (ICFMH). A Workshop. Behaviour of gram-negative pathogens on refrigerated foods. PMID- 1892737 TI - Public health implication of refrigerated pasteurized ('sous-vide') foods. AB - Food that upon pasteurization is stored in hermetically sealed containers at food temperatures not exceeding 3 degrees C could be designated by the generic term Refrigerated Pasteurized Foods of Extended Durability, REPFEDs. If not properly processed or protected against recontamination, or if temperature-abused, REPFEDs may present serious health risks. However, control is readily available. Sound microbial ecology, supported by expert risk assessment, allows the design and introduction of longitudinally integrated manufacture, distribution, handling by outlets and consumers and culinary preparation, which result in the assurance of the wholesomeness of the commodity as eaten. Recent progress, including intrinsic preservation by the incorporation of starter cultures, bacteriocins or particular enzymes, opens vistas for attractive future developments. Once microbiological safety has been built into the REPFED-line, monitoring can be limited to (i) real time tests particularly applied to the factory environment; and (ii) rapid, simple examination for marker organisms of freshly manufactured products versus those approaching expiration dates. Such audits will allow rapid retrieval of incidental process failure and its rectification. It also serves to substantiate measurements of food temperature and spot checks on intrinsic inhibitory attributes. The application of scientific knowledge and technological expertise should primarily be entrusted to the industry itself, heeding Lord Plumb's strategy of "partnership along the food production chain from farm to fork." It should be supported and validated by Public Health Authorities. At all stages safety communication with the public should be ensured. PMID- 1892738 TI - Psychrotrophy and foodborne Salmonella. AB - Recent reports on the behaviour of Salmonella at chill temperatures (less than 10 degrees C) raise concerns on the purported safety of refrigerated foods. The propensity for growth of salmonellae within 10-28 days in complex broth (5.9 degrees C) and agar (4.0 degrees C) media is overshadowed by more recent evidence on their capability to proliferate in fresh meats (2.0 degrees C) and shell eggs (4.0 degrees C) within 6 and 10 days, respectively. Such findings, together with the inability of many domestic refrigerators to maintain uniformly cold temperatures, are disquieting. Gaseous mixtures of CO2, N2 and O2 are widely used to extend the shelf life of chilled foods, notably fresh meats. The high levels of CO2 used in modified atmosphere packaging or generated by endogenous microflora in vacuum-packaged foods effectively inhibit the growth of psychrotrophic spoilage bacteria. Current evidence suggests that this industrial practice also arrests the growth of Salmonella but exerts little or no effect on their survival. Enhancement of the bacteriostatic potentials of pH and NaCl as temperature deviates from the optimum for growth to lower values could further contribute to the safety of chilled foods. PMID- 1892739 TI - Behavior of Aeromonas species at refrigeration temperatures. AB - The ability of many strains of Aeromonas hydrophila and A. sobria to produce several types of virulence factors has been documented. The presence of Aeromonas in drinking water, as well as in river and saline waters and on various finfish and shellfish taken from them, has caused some concern relative to the role this bacterium plays as a causative agent of human gastroenteritis. The fairly common occurrence of Aeromonas on red meats, poultry and fresh produce and its ability to grow at 4 degrees C gives rise to further concern over public health risks which may be associated with consumption of these foods. A brief overview of the behavior of Aeromonas species at refrigeration temperatures is presented. PMID- 1892740 TI - Practical monitoring of the chill chain. AB - Monitoring of temperature of chilled products at fresh food terminals is integrated into the quality assurance program of a retail chain. Each batch of products is examined on the receiving dock and rejected if the temperature is found above 7 degrees C, 5 degrees C being the legal maximal temperature. Measurement of temperature of processed meat products delivered to our company over a period of 14 months indicates that temperature abuse of chilled foods is not uncommon. Consistent rejection of batches because of high temperature resulted in a drop in the number of violations. PMID- 1892741 TI - Aspects of the epidemiology of Yersinia enterocolitica: a review. AB - A review of works concerning different aspects of the epidemiology of human pathogenic Yersinia enterocolitica biogroup IV/serogroup O:3 (Y. enterocolitica O:3) is given. To investigate the epidemiology of Y. enterocolitica O:3 in Danish herds of pigs, tonsil swabs from 2218 freshly slaughtered pigs originating from 99 herds were examined. The organism was isolated from 25% of the pigs and from 82% of the herds. No herd management factor could be associated with the presence of the organism. The effect of slaughtering technique on surface contamination with Y. enterocolitica O:3 was investigated. 1256 pigs were slaughtered by different evisceration techniques. When a mechanical bung cutter was used instead of the traditional, manual evisceration the contamination was reduced markedly, especially when the rectum and anus were enclosed in a plastic bag prior to the removal of the gut. It was possible to reduce the rate of the surface contamination from 26% on the medial hind limb and 13% on the split sternum and surroundings to about 2% for both sampling sites. An investigation of the presence of Y. enterocolitica O:3 in meat and meat products in retail butcher's shops was performed. The organism was detected in 10 of 33 samples of minced pork and in three of 24 samples of minced beef, but in none of 32 samples of sliced vacuum packed, low to medium salt meat products. The positive minced beef samples were collected at butcher's shops from which positive samples of minced pork were found as well. It is concluded that Y. enterocolitica O:3 is common in pork with a risk of cross-contamination to other products for example ready-to-eat meat products that might be a source of human infection. PMID- 1892742 TI - Acquired immunodeficiency syndrome (AIDS) and sexually transmitted diseases. PMID- 1892743 TI - Q fever in 1988-1989. PMID- 1892744 TI - Genetic predisposition to cancer. PMID- 1892745 TI - Can we prevent breast cancer? PMID- 1892746 TI - Membrane-interactive lipids as experimental anticancer drugs. PMID- 1892747 TI - The effects of vasopressin infusion on hepatic haemodynamics in an experimental model of liver metastases. AB - Vasoactive drugs have a variety of effects upon splanchnic and hepatic haemodynamics which may alter tumour blood flow and potentiate the delivery of a chemotherapeutic drug to hepatic tumour. We have investigated the effects of vasopressin infusion on hepatic tumour blood flow in an experimental model of liver tumour. Hepatic tumour was induced by the intraportal inoculation of HSN sarcoma cells. Hepatic and splanchnic blood flow was determined using a dual reference microsphere technique before and after an intravenous infusion of vasopressin at a dose of 0.1 mU kg-1 min-1 for 10 min. There was a significant increase in systemic arterial blood pressure associated with a rise in portal venous inflow (P less than 0.01, Wilcoxen Signed rank Test) and a significant fall in hepatic arterial flow (P less than 0.05). The tumour: liver blood flow ratio was significantly increased by vasopressin infusion (P less than 0.02). Vasopressin infusion decreases hepatic arterial flow and increases tumour blood flow which may potentiate the delivery of a regionally delivered chemotherapeutic drug to hepatic tumour. PMID- 1892749 TI - Enhancement of antitumour activity of etoposide by dihydropyridines on drug sensitive and drug-resistant leukaemia in mice. AB - We recently reported that six 1,4-dihydropyridine derivatives out of 57 screened effectively over-came vincristine (VCR)-resistance in VCR-resistant (P388/VCR) leukaemia-bearing mice when the dihydropyridines and VCR were administered intraperitoneally (i.p.). Furthermore, among the six dihydropyridine derivatives, two compounds, NK-250 and NK-252, most effectively overcame VCR-resistance while exhibiting relatively low calcium antagonistic activity and toxicity. In this study, we examined whether NK-250 and NK-252 could potentiate the antitumour activities of etoposide in mice with drug-sensitive (P388/S) or VCR-resistant (P388/VCR) leukaemia cells when the anticancer agents and tumour cells were administered by various routes. In both groups of mice inoculated i.p. with P388/S- and P388/VCR-leukaemia cells, the oral (p.o.) administration of NK-250 combined with i.p. or intravenously (i.v.) administration of etoposide (ip-po-ip trials and ip-po-iv trials) dramatically potentiated the antitumour activity of etoposide. Although etoposide alone was less effective in treating mice inoculated i.v. with P388/S- and P388/VCR-leukaemia cells, p.o. administration of NK-250 combined with i.p. or i.v. administration of etoposide (iv-po-ip trials and iv-po-iv trials) potentiated the antitumour activity of etoposide to similar levels as in treating mice inoculated i.p. with leukaemia cells. These 1,4 dihydropyridines were therefore highly effective in potentiating anticancer drugs against both drug-sensitive and drug-resistant tumours. PMID- 1892748 TI - The relationships between glutathione, glutathione-S-transferase and cytotoxicity of platinum drugs and melphalan in eight human ovarian carcinoma cell lines. AB - The role of glutathione (GSH) and GSH-S-transferase (GST) activity in modulating the cytotoxicity of four platinum drugs and melphalan was evaluated in eight human ovarian carcinoma cell lines. The cell lines were established from solid and ascitic tumours from pretreated and untreated patients, and showed a wide spectrum of sensitivity to several platinum II and platinum IV drugs; cisplatin, carboplatin, CHIP and tetraplatin. Intracellular glutathione concentration measured in the cell lines showed a significant (P = 0.05) correlation with IC50 values for cisplatin (r = 0.91), carboplatin (r = 0.87) and CHIP (r = 0.88). The correlation between GSH levels and IC50 values for melphalan (r = 0.76) or tetraplatin (r = 0.60) was not as significant. GST activity showed no correlation with IC50 values, for the four platinum drugs. To determine the significance of the elevated GSH concentration in the refractory cell lines, the effect of D,L buthionine-S, R-sulfoximine (BSO) mediated GSH depletion on platinum drug cytotoxicity was examined in one of the most sensitive (CH1) and two of the least sensitive (relatively resistant; SKOV-3, HX/62) cell lines. Comparison was made with the effect of GSH depletion on melphalan cytotoxicity in these three lines. These lines were differentially sensitive to BSO, with the two most platinum drug resistant lines being more tolerant to BSO than the sensitive CH1 line. Depletion of cellular GSH, ranging between 61 and 88%, had a differential effect on the sensitivity to PtII vs PtIV drugs in the three cell lines: cytotoxicity of the PtIV drugs, tetraplatin and CHIP, was substantially enhanced in both the resistant and sensitive cell lines; in contrast, the cytotoxicity of the PtII drugs, cisplatin and carboplatin, was only significantly increased in one of the two relatively resistant lines (SKOV-3) and in the sensitive (CH1) line after GSH depletion. Moreover the dose modification factor (DMF) for the PtII agents were lower than those for PtIV agents in the three cell lines. The dose modification factor for tetraplatin after BSO treatment was similar to that observed for melphalan in all three cell lines. In the SKOV-3 cell line extending the BSO pretreatment period to 48 h from 24 h marginally reduced the cytotoxicity of cisplatin, whereas the cytotoxicity of the other three drugs remained similar to that observed after 24 h BSO pretreatment. In contrast, extending the BSO treatment to 24 h after drug exposure potentiated the cytotoxicity of cisplatin, CHIP and tetraplatin.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1892750 TI - Perforin expression in lymphocytes infiltrated to human colorectal cancer. AB - Perforin (PFP) is a cytotoxic protein released from killer cells. PFP immunoreactivity in human peripheral blood lymphocytes (PBL) and tumour infiltrating lymphocytes (TIL) was investigated immunocytochemically with the aid of an anti-PFP monoclonal antibody. PFP was detected in the cytoplasm of 10% of PBL. We performed a double staining of PFP+ cells with Leu11b/CD16, Leu2a/CD8, or Leu3a/CD4 and showed that PFP was produced by 9% of CD8+ cells and 18% of CD16+ cells but not by CD4+ cells. In 28 colorectal cancer tissues, PFP immunoreactivity was observed in the lymphocytes infiltrating to the tumour stroma. The PFP+ cells were most numerous in Dukes A and decreased in number according to the progression of tumours. The PFP+ cells in TIL exhibited the same phenotypes as those in PBL but the PFP+ cells were more numerous in CD8+ cells than in CD16+ cells at all stages. This study represents the first evidence that PFP is mainly secreted from CD8+ cells in tumour tissues. It is hypothesised that the decrease in the number of PFP+ cells in accordance with tumour progression may reflect the suppression of the hosts local immunity. PMID- 1892751 TI - 4-Hydroxyandrostenedione in the prophylaxis of N-methyl-N-nitrosourea induced mammary tumourigenesis. AB - We have examined the role of the aromatase inhibitor 4-hydroxyandrostenedione (4 OHA) in the prevention of mammary tumourigenesis in experiments involving 170 rats. We first demonstrated a prophylactic effect of 4-OHA (50 mg/week) in reducing tumour incidence over a 30 week period compared to controls (P = 0.04). We repeated the experiment to determine optimum dose and duration of therapy. Although 4-OHA again prevented tumour development (P less than 0.0005), there was no difference between the standard (50 mg/week) dose and the higher dose (100 mg/week). Rats were randomised at 30 weeks to either stop or to continue prophylactic therapy; marginal benefit in tumour free survival in continuing therapy was observed (P = 0.03). We conclude that 4-OHA is an effective agent in preventing carcinogen-induced mammary tumours in rats and further studies of the role of oestrogen synthesis inhibitors in the prevention of human mammary tumours may be indicated. PMID- 1892752 TI - Differences in EGF related radiosensitisation of human squamous carcinoma cells with high and low numbers of EGF receptors. AB - Previous studies have shown that the presence of epidermal growth factor (EGF) after irradiation enhanced the radiosensitivity of CaSki cells. To examine the role of EGF receptor density and related growth response in EGF associated radiosensitisation, four human squamous carcinoma cell lines were used. The total number of EGF receptors for HN5, A431, CaSki, and SiHa cells is 5.2 x 10(6), 1.6 x 10(6), 7.9 x 10(5) and 1.1 x 10(5) respectively, and the dissociation constant (Kd) for low affinity EGF receptors is 11.8, 3.8, 1.7 and 0.8 nM respectively. The Kd for high affinity receptors differs slightly among the four cell lines, 0.09 to 0.21 nM. EGF inhibited the growth of A431, CaSki, and HN5 cells, but stimulated the growth of SiHa cells. Due to the presence of 10 ng ml-1 EGF after irradiation, radiosensitivity enhancement associated with reduced shoulder size of the survival curve was observed. The extent of sensitisation was similar for A431, CaSki, and HN5 cells, with no effect on SiHa cells. At this concentration, EGF present during the clonogenic assay period after irradiation also reduced the plating efficiency (PE) of the monolayer cultures of A431, CaSki, and HN5 cells, but increased that of SiHa cells. The radiation response of mouse 3T3 cells (less than 5,000 receptors) was not sensitised by EGF. A similar level of radiosensitivity enhancement by EGF was observed for parental and conditioned A431 cultures. The conditioned cells were grown in 50 ng ml-1 EGF for 10 weeks and did not demonstrate growth inhibition and PE reduction by treatment with EGF. The EGF receptor numbers and binding affinity of these cells were the same as for the parental cells. The results from the conditioned cells support the hypothesis that EGF related radiosensitisation is EGF receptor density dependent. PMID- 1892753 TI - Effects of cyclosporin A on growth and polyamine metabolism of MOLT-4 T lymphoblastic leukaemia cells. AB - We have examined the effects of Cyclosporin A (CsA) on growth and polyamine metabolism of MOLT-4, human T lymphoblastic leukaemia cells to ascertain the role of the polyamine biosynthetic pathway in the antitumour action of CsA. We observed that CsA had a dose-dependent inhibitory effect on growth of the cells in vitro, decreasing protein content, cell number and the rate of incorporation of 3H-thymidine into the cells. However, CsA treatment had no significant effect on intracellular polyamine levels in the cells. Contrary to previous reports, simultaneous addition of the diamine, putrescine, with CsA did not block or lessen the growth inhibitory effects of CsA. On the other hand, ornithine decarboxylase activity, the rate limiting enzyme of polyamine biosynthesis which converts ornithine to putrescine, was decreased by CsA treatment. This decrease appeared to be reversible and contrasts with the inhibition by alpha difluoromethyl-ornithine, which is irreversible and can be overcome by addition of putrescine. This suppression of ornithine decarboxylase by CsA is more likely to occur by indirect effects on translation and/or transcription rather than a direct effect on the enzyme. It may be a contributory factor in the overall antiproliferative effects of CsA but is more likely to be a response to these growth inhibitory effects rather than a direct effect of the drug. PMID- 1892754 TI - An evaluation of ovarian carcinoma-associated antigen defined by murine monoclonal antibody CF511 in sera from patients with ovarian carcinoma. AB - Murine monoclonal antibody CF511, raised against human ovarian clear cell carcinoma, detects a glycoprotein (Mr 600 kDa) called CF511 antigen which is elevated in the serum of many patients with ovarian carcinoma. A competitive enzyme-linked immunosorbent assay was developed to detect CF511 antigen in human serum and used to detected CF511 antigen in subjects with ovarian carcinoma and other diseases. No raised levels (less than 18 unit (U) ml-1) of the antigen were found in the serum of 220 normal individuals or of patients with germ cell tumours (n = 6), granulosa theca cell tumour (n = 1), gastric carcinomas (n = 10) and colo-rectal carcinomas (n = 8). Raised serum levels of CF511 antigen were found in 6/46 patients (13.0%) with benign gynaecological tumours (including endometriosis or ovarian cyst), in 5/7 patients (71.4%) with breast carcinoma and 16/21 (76.2%) lung carcinoma patients. In patients with ovarian carcinoma, 42.3% (11/26) of stage I and II, and 96.0% (24/25) of stage III and IV had levels of greater than or equal to 18 U ml-1. In all patients with serial determination of CF511 antigen levels before and after the surgery, the levels of antigen correlated with the clinical course of disease. Determination of CF511 antigen levels may be useful for detection of ovarian carcinoma as well as lung and breast carcinomas and for monitoring progress of disease and response to therapy. PMID- 1892755 TI - Resistance to the antimitotic drug estramustine is distinct from the multidrug resistant phenotype. AB - Following EMS mutagenesis, three estramustine (EM) resistant DU 145 human prostatic carcinoma cell lines were clonally selected by exposure to incrementally increasing concentrations of the drug. Although only low levels of resistance (approximately 3-fold) were attainable, this resistance was stable in the absence of continuous drug exposure. These EM-resistant clones (EMR 4,9,12) did not exhibit cross resistance to vinblastine, taxol, or adriamycin, and had collateral sensitivity to cytochalasin B. None of the lines had elevated expression of P-glycoprotein mRNA or glutathione S-transferase activity, suggesting a phenotype distinct from the classic multi-drug resistance phenotype. This conclusion was supported further by the observation that two MDR cell lines (FLC mouse erythroleukaemic and SKOV3 human ovarian carcinoma cells) showed sensitivity to EM. Fluorescent activated cell sorting analysis of the effects of EM on cell cycle traverse revealed that at EM concentrations up to 20 microM an increasing percentage of wild type cells were blocked in G2/M; no such effect occurred in EMR lines. Differential interference contrast microscopy was employed to study EM's effect on mitosis. EMR lines were able to form functional, albeit smaller, spindles at EM concentrations that resulted in chromosomal disorganisation and inhibition of mitotic progression in wild type cells. EMR lines were able to progress through mitosis and cytokinesis at the same rate as untreated cells. Tritiated EM was used to evaluate potential drug uptake/efflux mutations in ERM clones. EMR 4 and 9 incorporate less EM than wild type cells; however, they have significantly decreased cellular volumes. The initial efflux rate constants for EMR clones were greater than for wild type cells. Within 5 min greater than 70% of the drug was lost from resistant cells compared to a 50% loss by the wild type. Although the specific mechanisms of resistance have yet to be defined, the lack of collateral resistance to other MDR/anti-microtubule agents could serve as the basis for the clinical use of EM in combination chemotherapy. PMID- 1892756 TI - Xenogeneic monoclonal antibodies in the management of cancer: control of their in vivo immunogenicity and induction of specific unresponsiveness using an antibody drug immunoconjugate. AB - A bispecific mouse monoclonal antibody (mAb) that recognises carcinoembryonic antigen (CEA) with one binding site and vinblastine (VLB) with the other was used, and its in vivo immunosuppressive effect specific for anti-mouse immunoglobulin (Ig) was studied. The antibody was incubated with VLB at a molar ratio (MR) of 1:1, and administered i.v. to rabbits. Control animals received either the MAb alone, or the MAb with VLB covalently linked (MR 1:1), or the parental anti-CEA with equimolar amount of VLB. Seven days later, the rabbit anti mouse Ig primary response was measured, and found to be almost 55% reduced in the animals that received the VLB 'loaded' MAb. In vivo kinetics and stability experiments revealed that the T1/2 of the MAb was 68 +/- 5 h, whereas free VLB disappeared within minutes. It was concluded that as soon as the drug dissociates from the antibody's binding site, it is rapidly removed. This problem was overcome by subcutaneously implanting osmotic mini-pumps containing VLB. The pumps released the drug at a constant rate for a period greater than 1 week, saturating the antibody's binding site. Under these conditions rabbits developed 80% less anti-mouse Ig antibodies when the bispecific antibody was administered (compared with the parental anti-CEA). The immunosuppression observed was specific for the mouse Ig, under conditions compatible with the full clinical therapeutic potential of the MAb. In conclusion, these experiments show, that it is possible to develop hybrid antibodies that can act as a 'lethal bait' to any specific lymphocyte in vivo, thus preventing undesirable responses against the xenogeneic MAb. PMID- 1892757 TI - Cis dichlorodiammine platinum induced DNA interstrand cross-links in primary cultures of human ovarian cancer. AB - We quantified and examined the kinetics of DNA interstrand cross links (DNA-ISC) caused by Cis dichlorodiammine platinum (DDP) using the method of alkaline elution in 58 highly purified human ovarian tumours growing in primary culture. A large heterogeneity in both the quantity and kinetics of DDP induced DNA-ISC was observed in cultures derived from neoplasms of different patients and from different lesions of the same patient. In the majority of cases. DNA-ISC lasted for prolonged time intervals after 1 h drug exposure, being significantly repaired only 48 or 72 h following drug washout. The persistence of DNA-ISC is probably due to a prolonged formation of these lesions for up to 24 h as assessed by the change in the repair kinetics that occurred after preventing new DNA-ISC formation by quenching of monoadducts with thiourea. The inefficient repair of DDP monoadducts appears therefore to be a possible reason for the permanence of DNA-ISC. These studies suggest that the long permanence of DNA-ISC in human ovarian cancer could be the basis for the high selectivity of DDP for this human malignancy. PMID- 1892758 TI - The uptake and retention of metaiodobenzyl guanidine by the neuroblastoma cell line NB1-G. PMID- 1892759 TI - Sarcomas in north west England: I. Histopathological peer review. AB - A total of 468 cases of bone, soft tissue and visceral sarcomas (and certain other tumours) diagnosed during the years 1982-84 in North West England were entered in a study of histopathological peer review, incidence and survival. This paper describes the effects of peer review. Material was reviewed by a panel of five pathologists for 413 of the 450 cases originally registered as sarcomas with the Regional Cancer Registry. The diagnosis of sarcomas was confirmed in 76% cases and and there was agreement on sub-type for 53% cases. Measures of agreement were lowest for the two sub-types most commonly diagnosed i.e. malignant fibrous histiocytoma and leiomyosarcoma. Degree of agreement between individual pathologists and final panel diagnosis was also very variable but never less than 65%. It is concluded that second opinion is essential in cases of presumed sarcomas for studies of incidence and aetiology and to ensure that appropriate treatment is selected. PMID- 1892760 TI - Flow cytometric DNA ploidy pattern in dysplastic mucosa, and in primary and metastatic carcinomas in patients with longstanding ulcerative colitis. AB - Eighty-nine fresh tissue samples from flat colonic mucosa, polypoid lesions, macroscopically evident carcinomas, and metastatic carcinomas from ten patients with longstanding ulcerative colitis (greater than or equal to 8 years duration) were analysed by DNA flow cytometry and light microscopy. Of a total of ten carcinomas found in six patients, six showed DNA aneuploidy. Three patients developed metastatic carcinomas, all with aneuploid cell populations with similar DNA indices as in the primary carcinoma. Furthermore, aneuploid cell populations with similar DNA indices often occurred, both in separate mucosa samples, as well as in mucosa and carcinoma samples, from the same patient. DNA aneuploidy was found in flat mucosa in five of the six patients with carcinoma, and in one of the four patients without carcinoma (P greater than 0.1). High grade dysplasia was found in only four of the six cases with carcinoma, indicating that high grade dysplasia is insufficient as marker for malignant development. DNA aneuploidy was found in 24% of the dysplastic mucosa samples, and in 18% of the non-dysplastic mucosa samples (n.s., both with regard to high and low grade dysplasia). Since abnormal DNA ploidy pattern was not confined to dysplastic epithelium only, DNA aneuploidy in flat mucosa may constitute an additional marker in the identification of patients at increased cancer risk who could benefit from a closer surveillance. PMID- 1892761 TI - The roles of age and sex in the prognosis of chronic leukaemias. A study of 373 cases. AB - The roles of age and sex and their relationship to other prognostic factors were studied in 117 chronic myeloid leukaemia (CML) and in 256 chronic lymphocytic leukaemia (CLL) patients. Survival in CML was not related either to age at diagnosis or to sex. In contrast, the CLL patients classified into four age strata (less than 50, 50-59, 60-69, greater than 70 years) had an expected median survival (EMS) of 142, 101, 85 and 33 months respectively (chi 2 for heterogeneity = 35.59, P less than 0.0005; chi 2 for trend = 25.09, P less than 0.0005). Prognostic power was independent of sex, Rai stages, total tumour mass score (TTM), TTM distribution pattern, anaemia, thrombocytopenia, serum immunoglobulins and response to therapy. The relative survival rate (the ratio of patient's EMS and EMS in age- and sex-matched general population) was 0.40 in CLL patients and 0.13 in CML patients. Relative survival was more reduced in older CLL patients than in younger ones (0.37 vs 0.47, respectively), whereas relative survival was less reduced in older CML patients than in younger ones (0.18 vs 0.12, respectively). The results show that the age is a significant independent prognostic factor in CLL but not in CML. The difference in the effects of age on prognosis in CLL and CML most probably reflects the fundamental differences in their respective pathogeneses. PMID- 1892762 TI - Psychiatric morbidity in patients with advanced cancer of the breast: prevalence measured by two self-rating questionnaires. AB - Two hundred and twenty-two women with advanced cancer of the breast were asked to complete two previously validated self-assessment questionnaires (Hospital Anxiety and Depression Scale (HADS) and the Rotterdam Symptom Checklist (RSCL) in order to determine the prevalence and persistence of affective disorders in this group of patients. Fifty-six (27%) of 211 women who completed the HADS and 33 (22%) of 204 who completed the RSCL rated as probable cases of an anxiety state and/or depressive illness. One hundred and fifty-five patients completed the questionnaires again 1-3 months later. Twenty-one (13%) were persistently anxious or depressed as judged by the HADS compared with 14 (10%) on the RSCL. When both questionnaires were considered together, approximately one third of patients had scores suggestive of an affective disorder and in one third of these it was persistent. Only 30 patients (43% of cases) were detected as 'cases' by both questionnaires and this finding warrants further investigation. PMID- 1892763 TI - Screening for psychiatric morbidity in patients with advanced breast cancer: validation of two self-report questionnaires. AB - Eighty-one patients with advanced breast cancer completed the Hospital Anxiety and Depression Scale (HADS) and Rotterdam Symptom Checklist (RSCL) to determine how well these questionnaires identified patients suffering from an anxiety state or depressive illness, compared with an independent interview by a psychiatrist who used the Clinical Interview Schedule. A threshold score was defined for each questionnaire which gave the optimal sensitivity and specificity. Seventy-five per cent of patients were correctly identified as suffering from an affective disorder by both the Rotterdam Symptom Checklist and by the Hospital Anxiety and Depression Scale. Twenty-one per cent of 'normal' patients were misclassified by the Rotterdam Checklist and 26% by the Hospital Anxiety and Depression Scale. When the HADs anxiety and depression subscales were analysed separately, the performance of the anxiety items was superior to that of the depression items. Both questionnaires were found to have good predictive value and could be used in patients with advanced cancer to help screen out those with an affective disorder. PMID- 1892764 TI - Proliferation in human bladder carcinoma measured by Ki-67 antibody labelling: its potential clinical importance. AB - Ki-67 is a monoclonal antibody which recognises a human nuclear antigen expressed in proliferating cells. The antibody was used to assess proliferation in primary human bladder tumours from 64 patients. Ki-67 index (the number of Ki-67 positive tumour cells divided by the total number of tumour cells %) was derived from 59 tumours. A wide range of Ki-67 indices were recorded, range 3.0-65.8%, mean 20.2%. The Ki-67 index correlated with known prognostic factors: T stage (P = 0.002) and histological grade (P less than 0.001), early stage disease and more differentiated tumours having lower Ki-67 indices. Patients with invasive disease (21 patients) had significantly higher Ki-67 indices than those with non-invasive disease (P = 0.01). Patients with metastatic disease at presentation (four cases) all had a Ki-67 index of greater than or equal to 29%. Ki-67 antibody staining is a simple technique for assessing the proliferation fraction than can be performed on a small amount of tissue taken at routine biopsy without prior injection of thymidine analogues. PMID- 1892765 TI - A phase II study of epidoxorubicin in colorectal cancer and the use of cyclosporin-A in an attempt to reverse multidrug resistance. AB - We determined the ability of the multidrug resistance (MDR) reversal agent cyclosporin-A to increase anthracycline drug accumulation in colorectal tumour cells in vitro, using the technique of on-line flow cytometry. Data of four previously untreated patients showed that cyclosporin-A can increase intracellular net-uptake of daunorubicin. A phase II study was initiated in 24 colorectal cancer patients. They received cyclosporin-A at a dose of 3 mg kg-1 over 1 h as i.v. infusion, at 7 h and at 1 h preceding cytotoxic drug administration. At the end of the second cyclosporin-A administration epidoxorubicin 90 mg m-2 was administered as i.v. bolus. Cycles were repeated every 3 weeks. Median cyclosporin-A peak blood levels and levels at 18 h after cytotoxic drug administration appeared to be 6248 ng ml-1 and 1012 ng ml-1 respectively. Only one partial response was observed, despite these high cyclosporin-A levels. Cyclosporin-A did not cause major toxicity, only a 29% incidence of hot flushes was observed. Epidoxorubicin toxicities were as expected but the frequency of severe leucocytopenia was striking. This treatment schedule can not be considered active in colorectal cancer. PMID- 1892766 TI - Regional chemotherapy for inoperable renal carcinoma: a method of targeting therapeutic microspheres to tumour. AB - Regionally-administered, drug-loaded microspheres have a potential role in the treatment of renal tumours. Vasoactive agents, for example, angiotensin II, may allow selective delivery of microspheres to tumour. The present study defines the regional advantage that may be obtained from angiotensin II by quantifying tumour and normal kidney blood flow using radiolabelled microsphere renal perfusion studies and per-operative laser-doppler flow measurements. Angiotensin II increased microsphere distribution to tumour, relative to normal kidney, by a factor of four. This enhancement was associated with an absolute increase in tumour blood flow. PMID- 1892767 TI - Inter-clinician agreement on the recognition of clinical pigmentary characteristics of patients with cutaneous malignant melanoma. Studies of melanocytic nevi, VI. AB - The number and type of melanocytic nevi are among the most important known predictors of risk for cutaneous malignant melanoma. In this study, examinations of the skin were conducted by two to four clinicians on 153 patients with newly diagnosed melanoma, and the agreement among clinicians was quantified regarding number of nevi and freckling. The index of agreement (calculated as the intra class correlation coefficient) was 59.7% and 69.0% for freckling on the right forearm and on the shoulders, respectively; agreement was above 50% for only one of six pairs of clinicians in examining freckling on the right forearm, while agreement was above 50% for four of the six pairs of clinicians in examination of freckling on the shoulder. For palpable nevi of the arms (used in at least two case-control studies as a predictor of risk), the agreement was 36.1% when computed for three examiners assessing 81 patients. However, for total arm nevi (both palpable and non-palpable), assessed on a subset of 48 patients, the agreement was 88.2%; this and other analyses indicated that the difficulty in achieving a consensus for palpable nevi lay in whether or not lesions were considered to be 'palpable' or 'non-palpable'. Agreement for total number of atypical nevi on the body and total number of all types of nevi were 87.4% and 91.8% respectively. These data suggest that the kinds of lesions on which agreement might be reached are total atypical nevi and total nevi of all types on the arms and on the entire body. Greater difficulty might be found in achieving consistency among investigators and among clinicians in examining individual patients with respect to freckling on the arms and 'palpable' nevi. However, some consistency was achieved even with these latter two clinical features. PMID- 1892768 TI - Further evidence of an excess of risk of pleural malignant mesothelioma in textile workers in Prato (Italy). PMID- 1892769 TI - The prognostic value of the monoclonal antibody (D5) detected protein, p29, in primary colorectal carcinoma. PMID- 1892771 TI - Abnormally-fucosylated haptoglobin: a cancer marker for tumour burden but not gross liver metastasis. AB - A previous study has shown that there are high levels of an abnormally fucosylated form of haptoglobin (FHp) in the blood of cancer patients (Thompson & Turner, 1987b). In this study, we investigated the expression of this substance in serial blood specimens from women with ovarian or breast cancer who were undergoing cytotoxic chemotherapy. The level of FHp was related to patient response to therapy status, this latter index being an indirect determination of tumour burden. FHp levels did not correlate with gross liver metastasis (as shown by CT scans or the blood levels of liver enzymes). This conclusion was further supported by results from patients with hepatocellular cancer. FHp was elevated in most of these patients, but the pattern of change did not correlate with variations in the level of the hepatoma marker, alpha-foetoprotein. It seems likely that FHp is produced by the liver. Primary and secondary tumours could release substances, such as cytokines, which interfere with fucose metabolism in the liver. PMID- 1892770 TI - Rapid VAC high dose melphalan regimen, a novel chemotherapy approach in childhood soft tissue sarcomas. AB - Forty-three children with malignant soft tissue sarcomas (IRS Groups II-IV) were treated with rapid dose delivery chemotherapy protocol comprising six courses of vincristine, adriamycin and cyclophosphamide, given in most cases within 8 weeks (Rapid VAC). This was followed in 36 patients by high dose melphalan with autologous bone marrow rescue. Twenty-six patients also received irradiation to the site of primary tumour. The Rapid VAC regimen was well tolerated and largely administered as an out-patient. There was one toxic death which occurred 2 months after high dose melphalan due to a combination of infection and possible anthracycline cardiomyopathy. Stages were, (Intergroup Rhabdomyosarcoma Study (IRS) system) Group, Group II--four patients. Group III--27 patients and Group IV -12 patients; International Society of Paediatric Oncology (SIOP) staging, Stage I--11, Stage II--13, Stage III--7, Stage IV--12. Actuarial survival at 5 years for all stages is 57% and event free survival 44%. For patients with non metastatic diseases, 62% and 53% respectively. This treatment strategy utilises the philosophy of rapid drug delivery with high dose consolidation and enables all chemotherapy to be finished within a 4 month period. In general, a conservative approach was applied to both radiation and surgery to minimise late sequelae related to these treatment modalities. Although the small number of high risk patients in this study limits conclusions regarding efficacy in these subgroups the overall results with this regimen appear to be comparable to that with other approaches. PMID- 1892772 TI - Oncologists vary in their willingness to undertake anti-cancer therapies. AB - Previous studies have shown that groups of cancer sub-specialists differ in their stated willingness to undergo treatment for diseases lying within their area of expertise. In order to learn whether oncologists feel similarly about other forms of cancer, medical, radiation, and surgical oncologists were asked to fill out a questionnaire indicating whether they would be willing to undergo either chemotherapy or radiation therapy for a variety of common malignancies, or recommend them to a spouse or sibling. Subjects were also asked whether they would undertake an experimental therapy (interleukin-2) for any of three malignancies, or recommend such treatment to a spouse or relative. Fifty-one oncologists (14 radiation oncologists, 14 surgical oncologists, and 23 medical oncologists) were recruited from the staff of four university teaching hospitals. Although they agreed about accepting or declining therapy for some examples, there was considerable heterogeneity in their responses. In only 37% of the 30 cases involving standard therapies did greater than or equal to 85% of the oncologists agree that they would accept or refuse therapy. Only some of the variation of the responses could be attributed to the sub-specialty orientation of the oncologists. Physicians were as willing to recommend standard therapies for themselves as a spouse or sibling. Physicians were also divided in their opinion about whether they would accept a particular experimental therapy if diagnosed with one of three neoplasms. They were significantly more likely, however, to recommend it for a spouse or sibling than to accept it for themselves. Variation in the proportion of patients who receive anti-cancer therapies may relate, in part, to differences in opinion concerning the worth of such therapies among oncologists or primary physicians. This study shows that oncologists are quite heterogeneous with regard to their personal preferences for anti-cancer treatments for a variety of malignancies. Further studies are required to learn if such attitudes (among oncologists or primary physicians) directly affect the administration of such therapies. PMID- 1892773 TI - Palliation and life quality in lung cancer; how good are clinicians at judging treatment outcome? AB - A recent trial by the MRC Lung Cancer Working Party used physician assessments to compare two palliative schedules of radiotherapy in lung cancer. A prospective study has been undertaken on a subset of these trial patients to see how physician assessments of symptomatic relief and general condition correlate with patient perception of therapeutic response. In 40 patients followed up monthly from presentation until close to death, good agreement was found between doctors and patients on change in specific physical symptoms and overall physical condition. Doctors were poor judges of life quality at presentation but appeared able to identify relative improvement or deterioration in overall quality of life. In conclusion, physician assessments may constitute valid end-points for radiotherapy trials comparing palliative schedules in lung cancer. PMID- 1892774 TI - Glomerular filtration rate, 131I-hippuran clearance and estimated creatinine clearance in cancer patients. AB - Glomerular filtration rate (GFR), 131I-Hippuran clearance and estimated creatinine clearance were investigated in 34 patients with cancer. For Hippuran clearance and GFR, analysed with the X-ray contrast (iohexol) and fluorescence technique, the least square linear regression coefficient was 5.01 +/- 0.41 (r = 0.91). This value concurs with the five to one ratio between GFR and renal plasma flow known from normal physiology and supports that Hippuran clearance is a valid measure of renal function. When the individual values of Hippuran clearance were divided by 5.01, the mean difference between the methods was 0.4 ml min-1 1.73 m 2 with standard deviation 13.4 ml min-1 1.73 m-2. The lower and upper limits of agreement were -26.7 and 25.9 ml min-1 1.73 m-2, respectively. Comparing creatinine clearance estimated from the serum creatinine level with GFR, the limits of agreement were -29.4 and 21.6 ml min-1 1.73 m-2. These agreement limits are in the same range as those which can be calculated from the data from other studies. PMID- 1892775 TI - A randomised trial comparing combination chemotherapy using mitomycin C, mitozantrone and methotrexate (3M) with vincristine, anthracycline and cyclophosphamide (VAC) in advanced breast cancer. AB - This paper describes a randomised clinical trial in patients with advanced breast cancer, comparing the regimen 3M, mitomycin C 7-8 mg m-2 (day 1), mitozantrone 7 8 mg m-2 (day 1 and 21), methotrexate 35 mg m-2 (day 1 and 21) given on a 42 day cycle with a standard anthracycline containing regimen, VAC, vincristine 1.4 mg m 2 (day 1), anthracycline (adriamycin or epirubicin) 30 mg m-2 (day 1), cyclophosphamide 400 mg m-2 (day 1) given on a 21 day cycle. Of a total of 217 patients, 107 were randomised to 3M and 110 to VAC and a mean of 5.5 courses was given per patient. The overall response rate (complete and partial) was 53% (95% Confidence Limits (CL): 43-62%) for 3M and 49% (CL; 39-58%) for VAC. The response according to sites of metastases was the same for both treatment groups. Symptomatic toxicity including alopecia, neuropathy, vomiting (P less than 0.001) and nausea (P less than 0.01) were significantly less for 3M. Myelosuppression including leucopenia (P less than 0.001) and thrombocytopenia (P less than 0.001) was significantly greater with 3M at day 21, although there was no difference in nadir counts in patients at special risk of myelosuppression and there was no evidence of an increase in infective or bleeding complications. There was no significant difference in the duration of response to 3M (10 months, CL 6-15) and VAC (11 months, CL 7-12), nor in survival (3M, 8 months, CL 6-12; VAC, 10 months, CL 8-12). These results indicate that 3M is as effective as, but has significantly less symptomatic toxicity than, an anthracycline containing regimen for the treatment of advanced breast cancer. PMID- 1892776 TI - No N-ras mutations in human uveal melanoma: the role of ultraviolet light revisited. PMID- 1892777 TI - Psychomotor functioning in unipolar and bipolar affective disorders. AB - The performances of unipolar and bipolar depressive patients and also of a control group on motor, verbal and mental components of psychomotor functioning were clinically and psychometrically evaluated and compared at a univariate and multivariate level. The groups were similar with respect to age, sex, educational level, illness onset age and depression severity. In univariate comparisons of test-based assessments of psychomotor functions the overall tendency was towards a more pronounced retardation in unipolar depressive patients compared to bipolar ones and controls, the differences being marked on some measures and relatively small on others. Multivariate analyses using scores on 20 psychomotor variables revealed a rather good discrimination of the depressive groups, 78.57% of cases being correctly classified, with 0.80 sensitivity for unipolar patients and 0.75 specificity. Clinical evaluation of spontaneous psychomotor activity did not reveal notable differences between the two depressive groups. PMID- 1892778 TI - Migraine-related stroke. A review. PMID- 1892779 TI - Clinical, computerized EEG and polysomnographical studies in some myoclonic syndromes. AB - Forty-two patients with myoclonic manifestations (especially during subacute sclerosing panencephalitis (SSPE)) were studied. The multidimensional investigations pointed out that myoclonias produce several EEG and polysomnographical perturbations: 1. Sleep disorganization; 2. Appearance of the myoclonic jerks in wakefulness (especially) and in some sleep stages; 3. Some electroclinical discordances; 4. A great variability of the myoclonias during some sleep stages; 5. EEG cortical mappings showed individual variabilities of Radermecker complexes. PMID- 1892780 TI - Polysomnographical researches in patients with temporal lobe epilepsy. AB - One hundred and twelve patients with temporal lobe epilepsy were studied. Continuous polysomnographical recordings were performed for eight hours, the patients being video-monitored all the time. These researches, completed with computerized EEG cortical mappings demonstrated a peculiar activation of the temporal foci during REM phases and during some stages of LSWS. PMID- 1892781 TI - Advances in the treatment of atherosclerosis. PMID- 1892782 TI - Cerebral dysfunction revealed by EEG mapping in the schizoform epileptic psychosis. AB - Twenty schizophrenia-like psychotic patients suspected of epilepsy were explored using EEG techniques (recordings in the 10-20 International System, source derivation, EEG mapping and EEG spectral reaction mapping by photic and somesthetic stimulation). In 16 of them, latent epileptic disorders were found. EEG spiking foci could be located either: (a) in temporal, (b) fronto-basal, or (3) in the sagittal-line leads. A corresponding associated dysrhythmia was clearly revealed by EEG mapping. On EEG spectral reaction mapping a suggestive aberrant displacement of the area of maximal sensory response was found. These EEG disorders were in significant relation with the psychotic syndrome observed in the respective group of patients: (a) patients with fronto-basal (temporal anterior) foci were prevalently paranoid; (b) patients with temporal lobe foci were prevalently depressive; (c) patients with sagittal line (singular) foci presented a predominantly expansive, hypomanic behaviour. The study shows the importance of normal fronto-limbic circuits for the preservation of mental health. PMID- 1892783 TI - EEG mapping in mentally retarded children by synthetic arginine vasotocin administration. AB - EEG investigations (using source-derivation) were performed in 15 mentally retarded children, before, during (at 1 and 6 months) and after three months of pineal hormone treatment (AVT, 10(-6) mg/day, intranasally). Power spectral analysis, maturation lines and EEG mapping were used to ascertain the functional changes induced by AVT. A rapid increase in maturation EEG coefficients was found. It resulted from a significant reduction in the percent amount of theta and delta activity and from the increase in alpha activity. A significant increase in alpha peak frequency occurred after 6 months of treatment as well as a better separation of the EEG patterns between the anterior and posterior halves of the hemispheres. These favourable effects were clearly evidenced by EEG mapping. They are in good relation with cognitive function (attention, intelligence) improvement induced by AVT therapy. PMID- 1892784 TI - The vomeronasal (Jacobson's) organ in man: ultrastructure and frequency of occurrence. AB - These investigations address three major questions: (1) What is the frequency of occurrence of the vomeronasal (Jacobson's) organ (VNO) in man? (2) what is the ultrastructure of the human VNO? and (3) does the VNO contain sensory receptor cells? Macroscopic and microscopic intranasal clinical examinations of over 200 persons revealed paired bilateral vomeronasal pits on the anterior 1/3 of the nasal septum in all cases. Biopsies of the vomeronasal pits and surrounding tissues were examined by light and electron microscopy. These studies showed that the vomeronasal pit leads to a closed tube, 2-8 mm long, lined by a unique pseudostratified columnar epithelium unlike any other in the human body. The anterior end of the tube is lined by tall, columnar cells with a sparse population of short microvilli. The posterior end of the VNO is lined by an epithelium that contains three morphologically distinct cell types: (1) basal cells; (2) "dark cells--tall, slender cells with heterochromatic nuclei and electron-dense cytoplasm that often contain mucigen-like granules; and (3) "light" cells--large, clear cells, extending from the basement membrane to the organ's lumen. Each "light" cell has a round, euchromatic nucleus and a clear cytoplasm that often contains many Golgi stacks and membrane-limited vesicles filled with material of modest electron density. The cell apex is tipped by a few short microvilli. Whether these cells subserve any sensory function awaits further investigation. PMID- 1892785 TI - Ultrastructure of the human vomeronasal organ. AB - Virtually all vertebrates have a vomeronasal system whose involvement in pheromone detection plays a crucial role in reproduction. In humans, the vomeronasal organ has been assumed to be vestigial or absent and without functional significance. In the present study involving over 400 subjects, vomeronasal pits were observed in all individuals except those with pathological conditions affecting the septum. Electron microscopy of the adult human vomeronasal organ indicates the presence of two potential receptor elements in the pseudostratified epithelial lining: microvillar cells, and unmyelinated, intraepithelial axons. In addition, unmyelinated axons are common in the lamina propria surrounding the organ. They appear to constitute the components essential for a functional chemosensory system, and may thus provide the basis for a pheromone detection system as in other animals. PMID- 1892786 TI - The incidence of the vomeronasal organ in 1000 human subjects and its possible clinical significance. AB - The 1000 subjects randomly selected were evaluated for the presence of the vomeronasal organ (VNO). The results of the present investigation indicated the presence of the VNO in almost every subject studied. The implications of the presence of the VNO and its clinical significance during nasal operations are considered. PMID- 1892787 TI - Migration of LHRH-immunoreactive neurons from the olfactory placode rationalizes olfacto-hormonal relationships. AB - Nerve cells that express luteinizing hormone-releasing hormone (LHRH), essential for reproductive functions, originate in the epithelium of the medial olfactory placode. While the peripheral origin of this physiologically important brain peptide is surprising, associations between olfactory and reproductive systems are well documented in behavioral studies of pheromones and in clinical studies of disorders including hypogonadotropic hypogonadism with anosmia or olfactory genital dysplasia. Mechanisms underlying this migration include a close association with neural cell adhesion molecules (NCAM), but are likely also to involve other physical and chemical factors. PMID- 1892789 TI - Toward a pharmacology of odor receptors and the processing of odor images. AB - Odor molecules may be considered as molecular ligands which bind to receptors in the olfactory sensory neurons to give rise to the sensory response. Binding studies in whole sensory epithelia suggest that the receptors also bind muscarinic cholinergic antagonists. Preliminary electrophysiological evidence indicates that muscarinic and beta adrenergic antagonists block odor-elicited membrane currents in single isolated salamander sensory neurons. These results support the idea that models developed for analyzing ligand binding by members of the 7 transmembrane domain family of membrane receptors may apply rather closely to olfactory transduction. We suggest that sensory neurons express single receptor types with differing degrees of affinity for different ligands. We further suggest that glomeruli in the olfactory bulb function as labeled lines for particular sets of odor ligand determinants, and that interglomerular circuits bind together similar glomeruli and enhance contrast between dissimilar glomeruli. The odor image laid down in the sensory neuron population is thus subjected to abstracting and enhancement at the glomerular stage, prior to being transmitted for further processing in the deeper layers of the olfactory bulb and in the olfactory cortex. PMID- 1892788 TI - Effect of putative pheromones on the electrical activity of the human vomeronasal organ and olfactory epithelium. AB - The summated receptor potential was recorded from the vomeronasal organ (VNO) and olfactory epithelium (OE) of 49 human subjects of both sexes (18 to 55 years old) using surface non-polarizable silver-silver chloride electrodes. 15-25 pg of human putative pheromones, clove oil and a diluent were administered to the VNO or the OE in 0.3-1 s pulses from a 0.05 mm dia cannula connected to a multichannel delivery system. Local stimulation of the VNO produces negative potentials of 1.8-11.6 mV showing adaptation. Responses are not obtained when the recording electrode is placed in the nasal respiratory mucosa. Pheromone ER-830 significantly stimulates the male VNO (P less than 0.01; n = 20), while ER-670 produces a significant effect on female subjects (P less than 0.001; n = 20). The other pheromones tested do not show significantly different effects in both male and female (P greater than 0.1). Similar quantities of odorant or diluent produce an insignificant effect on the VNO. Stimulation of the OE with clove oil produces depolarization of 12.3 +/- 3.9 mV, while pheromones do not show a significant effect. Our results show that the VNO is a functional organ in adult humans having receptor sites for human putative pheromones. PMID- 1892790 TI - Central processing of olfaction. AB - Studies on the properties of olfactory receptors and of the olfactory glomeruli indicate that there is spatial segregation of response to particular characteristics of odorant molecules at the input level of the olfactory bulb. Existing anatomical information and studies of synaptic mechanisms in the olfactory bulb suggest that the bulb circuitry might act as a contrast detection mechanism analyzing a spatially organized input. Recent electrophysiological studies have supported this idea. Extracellular recordings have shown that the similarity between responses of cell pairs to the same stimulus odor depend upon the distance between those cells. Intracellular recordings from mitral and tufted cells have shown spatially organized excitatory and inhibitory responses to localized electrical stimulation of the input layer of the bulb. Some of the major interneurons of the olfactory bulb have also been identified during odor and localized electrical stimulation. These recordings are also consistent with a spatially based organization. PMID- 1892791 TI - Sensory processing in the main and accessory olfactory systems: comparisons and contrasts. AB - The vomeronasal organ (VNO) and accessory olfactory system (AOS) are present in most terrestrial vertebrates except birds and higher primates. The receptor neurons of the AOS are sequestered inside the VNO, away from the main airflow to the main olfactory receptor neurons. Mechanisms of stimulus access to the sensory neurons vary across species but in most cases there is a system for delivering stimuli faster than would be possible by diffusion. Vomeronasal (VN) receptor neurons typically lack cilia, the site of most of the transduction apparatus in the main olfactory receptors. The VN receptor neurons have a restricted but privileged pathway to the areas of the brain concerned with reproduction and social behavior. In contrast, the main olfactory neurons have a broad pathway to wide areas of the brain, including the neocortex. Experiments where the VNOs or other parts of the accessory olfactory pathway were ablated indicate that the system is important in many behavioral and physiological responses to pheromones (chemical signals carrying information about gender or reproductive or dominance status), some of which may be proteins. VN sensory neurons respond to both volatile and non-volatile stimuli. There is no evidence in the vertebrate AOS for the extreme sensitivity or selectivity characteristic of insect pheromone detectors, but this has not been adequately tested. There is some evidence for learning, possibly by synaptic modification at the second-order neuron level. Social and reproductive cues stimulating the AOS often elicit an intracerebral release of LHRH--which may act at receptors different from those of the pituitary to facilitate behavior. Whether the LHRH release is necessary for AOS-mediated behavioral response is not yet clear. PMID- 1892792 TI - A chemistry of mammalian pheromones. AB - Many mammalian social odors do not elicit an observable specific response in the recipient and therefore strictly cannot be considered to be pheromones. The pheromones now known in mammals are mostly transferred by contact and detected by accessory olfaction, which further indicates that pheromones in mammals should not be considered to be even a subclass of social odors. Aphrodisin, a female hamster pheromone that elicits sexual behavior in male hamsters, is a member of the lipocalycin family of 20 kDa extracellular proteins, and it is most closely related to rat odorant binding protein. Homologous proteins occur in the urine and scent glands of mice, rats and possibly voles, where they may serve as pheromone binding proteins. A 20 kDa protein, pheromaxein, binds the known pheromones androstenol and related steroids in boar saliva, and uncharacterized small proteins have been found in monkey and human skin gland secretions. Thus it appears that proteins may generally be associated with mammalian pheromones. PMID- 1892793 TI - Sexual pheromones in the domestic sheep: importance and limits in the regulation of reproductive physiology. AB - In mammals, primer pheromones are considered as the most important signals involved in socio-sexual stimulation of the reproductive processes. In the domestic sheep, male-female interactions induce changes in the pulsatile rhythm of the LH secretion in both sexes which influences reproductive endocrinology. In the female, the odor of the ram's fleece induces LH secretion and ovulation. The acid sub fraction of the methylene chloride extract under C16 and diols appear to contain the active components. An interspecific action has been observed, as male goat's hair extract is similarly active. In the male, although the receptive female is the most effective to stimulate LH release, no pheromonal action has been demonstrated. In the female, lesions of the vomeronasal system do not eliminate the endocrine response to pheromonal stimulation. Furthermore, in both sexes, anosmia does not impair the response to direct interaction with the sexual partner. In domestic sheep, the existence of primer pheromones has been demonstrated, but other sensory cues could replace olfaction during socio-sexual interactions interfering with the control of reproductive endocrinology. PMID- 1892794 TI - Human exposure to putative pheromones and changes in aspects of social behaviour. AB - Student volunteers (38 of each sex) were exposed unknowingly overnight to the vapour of pheromonally active substances and compared with controls. The substances were either 5 alpha-16-androsten-3 alpha-ol (androstenol, occurring in human underarm sweat, and known to be pheromonally active in pig and man), or a mixture of short-chain fatty acids (occurring in human vaginal fluid, and known to be sexually attractive to the male rhesus monkey). The following morning, the subjects provided information about their social exchanges since rising, by recording on a standardized test diagram the number, depth, duration and direction of initiation, of all verbal exchanges with other individuals. Irrespective of treatment, males returned significantly higher scores than did females for all exchanges and also for some exchanges initiated by other males. Neither exposure to androstenol nor to the fatty acids had any significant effects on any of the scores of males interacting with either sex, nor on any scores of females with other females. However, exposure of females to androstenol, but not to the fatty acids, resulted in significantly higher scores of exchanges with males, in terms of all parameters for all exchanges. Findings are considered in relation to the origin and maintenance across species of pheromonal communication: evolutionary conservation is seen in terms of the utilization of substances that have provided the means of controlling the social milieu. PMID- 1892795 TI - Consequences of removing the vomeronasal organ. AB - In the last decade, research in our laboratories has focused on the effects of deafferentation of the mammalian chemosensory vomeronasal organ (VNX). Many different assays have been conducted and the results of some are briefly reviewed in this contribution, including the effects of VNX on neuroanatomical assessments using histochemistry (lectin binding) and immunohistochemistry (LHRH), male mouse and prairie vole ultrasonic vocalizations and hormone surges in response to cues from females, male mouse courtship and sexual behavior, territorial marking and inter-male aggression, the production of a puberty-altering substance found in mice, activation of reproduction in female voles (who generally do not exhibit estrous cycles) and maternal behaviors by female mice, including aggression directed toward intruder males. In some instances, the otherwise detrimental effects of VNX can be overcome by experience prior to deafferentation, especially in assays that are dependent upon expressions of behavior. In other situations, experience may have little impact on amelioration of the effects of VNX. The essential conclusions of this work focus our attention on reproductive physiology and behavior and a role for the vomeronasal organ in the perception of pheromones that modulate these functions. PMID- 1892796 TI - The human skin: fragrances and pheromones. AB - Non-human mammalian pheromones are commonly used as perfumery ingredients. The actual purpose for using these compounds is as a fixative or carrier for the odor effects of the other ingredients as well as a contributor, in part, to the over all scent of the perfume. Although such materials are used for their fixative and odor qualities rather than their pheromonal effects, perfumes are generally marketed as having the ability to enhance sexual attractiveness. While providing a scent may elicit a positive pleasant response, this should not be confused with a pheromone response. The attractive effect of perfumes is principally related to the effect of the pleasant scent. A more logical approach would be to use human pheromones which, for humans, are both more natural and more effective as true sensual attractants. It seems likely that implementation of this approach will constitute an important paradigm in the perfume industry as perfumery moves from the realm of art to that of science. PMID- 1892797 TI - Studies to be conducted before projected operations from the pediatric surgeon's point of view. AB - To rationally discuss the "need for preoperative laboratory investigations prior to performing an operation that can be pre-planned", two questions must be considered: 1. What kind of complications were encountered during or after 25,872 anesthesias performed in a 20-year period? 2. What kind of diseases were recognized only postoperatively which apparently could not be diagnosed preoperatively via case history and clinical examination? The results of these analyses are tabulated and assessed. It could be shown that the case history and the clinical examination of the patient on the day of surgery rank before all laboratory tests. With regard to peroperative respiratory disturbances it could be proven that children within the first trimester are particularly susceptible to such alterations. Furthermore, it could be demonstrated that within this group premature babies are more susceptible to this kind of complication than babies born at date. With regard to the incidence of preoperative respiratory disturbances in children with or without infection of the upper respiratory tract, it was shown that children without such symptoms who had however undergone an infection three to four weeks before the operation, were more susceptible to peroperative respiratory disturbances than children without any infection or even children suffering from an acute infection. Taking the physiological Hb decrease at the end of the first trimester as an example, questions on the optimal date for surgery are discussed. Preoperative handling is discussed on the basis of the blood glucose level of 500 children after a fasting period of 3-4 hours. PMID- 1892798 TI - Long-gap esophageal atresia: experience with reconstruction in 25 patients. AB - In a series of 183 patients with esophageal atresia in a period of 20 years, 25 had a "long-gap" esophageal atresia. In most of these cases we succeeded in saving the patients' own esophagus but at the cost of one to two years of intensive treatment. The overall survival was 80%. The result compares favorably with the results of esophageal replacement reported in the literature. PMID- 1892799 TI - Congenital esophagostenosis. AB - By means of two of our own cases we report on congenital esophagostenosis which occurs in a proportion of 1:50,000. The typical clinical symptoms consist of frequent vomiting, regurgitation of undigested food particles which have no acid smell, and regurgitation of viscous mucus and saliva. In the last decade direct operative treatment has taken the place of primary bougienage therapy. PMID- 1892800 TI - Ileus in the newborn: a study of decreasing mortality. AB - The authors' experience with operative therapy for ileus-duodenal, small intestinal, colon, and rectal-in newborns is presented with an analysis of the improvements in prognosis over the last 30 years. For the time period 1980-1989, the following survival rates were achieved: duodenum: 100%; small bowel: overall 96.8%, for uncomplicated cases 100%; congenital megacolon: overall 89%, for uncomplicated cases 100%; ileus of all intestinal portions together: 97.5%, for uncomplicated cases 100%. PMID- 1892802 TI - Embryonal rhabdomyosarcoma of the common bile duct. AB - A 2 4/12-year-old boy with obstructive jaundice caused by a tumor of the portal area that proved to be an embryonal rhabdomyosarcoma of the common bile duct is reported. The diagnosis was made clinically, radiographically, ultrasonographically, and histologically. Surgery was elected as the primary therapy; there were no intra- or postoperative complications. The prognosis and its improvement by means of aggressive chemotherapy and local irradiation are discussed. PMID- 1892801 TI - Biliary atresia--a 25-year survey. AB - In the past 25 years, from 1963 to 1988, 90 children from the Department of Pediatric Surgery of the Pediatric Hospital in Cologne, Germany were treated for biliary atresia. Of these, 47 had purely extrahepatic bile duct lesions, 21 had purely intrahepatic bile duct lesions, and 22 had both extrahepatic and intrahepatic bile duct lesions. Forty-five of the children underwent a drainage operation, whereas the remaining 45 children underwent no surgery at all or simply a diagnostic laparotomy. Until 1966 hepato-jejunostomy with implantation of artificial bile ducts was conducted in 12 cases. Later, cholecystoduodenostomy was performed 4 times and hepatoporto-jejunostomy according to Kasai-Kimura 29 times. The latter was performed either without and enterostomy (n = 16) or with an enterostomy in the respective intestinal loop (n = 13). 27 patients survived (30%). If only the children with intrahepatic bile duct hypoplasia are considered, the survival rate was 12 out of 15 patients (80%). Eight children (27.5%) of the 29 with hepatoporto-jejunostomy are still alive today. This survival rate, compared with the survival rate of the total, is comparably large with 27.7%. Current data from the 23 surviving patients was retrospectively gathered in our hospital or was collected from outside the establishment. It was analyzed with regard to prognosis and long-term results. Only in 5 of the 29 cases of children with hepatoporto-jejunostomy could a lasting postoperative biliary flow be achieved. Only one of the children can be classified as completely healthy in regard to his liver.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1892803 TI - The use of reduced-size liver transplants in children, including split livers and living related liver transplants. AB - One of the key problems facing children awaiting liver transplantation is the shortage of donor organs. Surgical procedures that address this problem include: reduced-size liver transplantation (RLT), split liver transplantation (SLT), and living related liver transplantation (LRLT). RLT makes more of the current donor pool accessible to the pediatric recipient. SLT furnishes 2 liver grafts from 1 cadaveric donor, and LRLT provides an innovative supply of donor organs. This report compares the results achieved with RLT, SLT, and LRLT to those seen with full-size orthotopic liver transplantation (OLT). Between November 1984 and February 1991, 457 liver transplants were performed at the University of Chicago. Two hundred fourteen of these transplants were placed into recipients less than 13 years of age. Of these 214 pediatric orthotopic liver transplants (OLT), 103 were full-size livers and 111 were some type of reduced graft (RLT, SLT, or LRLT). There were 57 RLT, 34 SLT, and 20 LRLT. The recipients of the reduced grafts (RLT, SLT, or LRLT) averaged 1.9 +/- 1.8 years of age and 9.6 +/- 6.4 kg compared to the recipients of the full-size livers who averaged 3.5 +/- 3.4 years of age and 14.1 +/- 8.8 kg (p = 0.0001). The most common indication for transplantation was biliary atresia (105 patients). Overall patient survival after primary full-size OLT was 71.8%. Reduced-size OLT (RLT, SLT, and LRLT) resulted in an overall patient survival of 72.6% after primary transplantation. Patient survivals for primary transplants with specific types of reduced-size grafts were: RLT 76.5% (after RLT was used routinely), SLT 66.7%, and LRLT 89.5%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1892804 TI - Ureterosigmoidostomy: a long-term follow-up of 15 patients with urinary diversion. AB - We reviewed 15 patients who underwent 16 ureterosigmoidostomies from 1975 to 1989. The underlying disease was bladder exstrophy in 13 patients. Urinary diversions have been performed according to Mathisen in 15 patients, one reoperation has been performed according to Coffey. Standard post-operative controls consist of physical examinations, capillary blood gas samples, intravenous pyelograms, inulin clearance measurements, 123I-hippuran scintigraphies and colonoscopies. Results concerning continence are judged very satisfactory in 80% of patients. 34% of patients presented with one or more episodes of unilateral or bilateral pyelonephritis. Intravenous pyelograms showed improved or unchanged urinary tract dilatation in 45% of kidneys and moderate and severe dilatation in 55%. Inulin clearance remained in normal range in 4 out of 6 patients followed. Renal function assessed by means of renal scintigraphy remained unchanged in 61% of kidneys, slightly decreased in 22% and severely in 17%. All patients are kept on a sodium-citrate therapy. Only one patient shows growth disturbances. Out of 9 patients followed with colonoscopy, none showed signs of malignancy. PMID- 1892805 TI - Neurogenic bladder in children: urodynamic studies and results with medical conservative treatment. AB - We present the urodynamic findings and therapeutic results in 25 children with neurogenic bladder, ranging in age from 2 months to 14 years. We observed a significant reduction of urinary infections and vesicoureteral refluxes following medical treatment based on the urodynamic findings. Furthermore, we observed a worse evolution in patients with pre-voiding bladder pressure in excess of 50 cm H2O, incontinence being more difficult to treat in children with urethral closure pressure profile below 47 cm H2O. In our series, anticholinergic treatment improved hypertonia and hyperreflexia which disappeared in 66.6% of cases. Total continence was achieved in 37.5% and improved in 29.1% of children. PMID- 1892806 TI - Urethral reconstruction using an autologous bladder mucosal graft. AB - Since 1988 twelve children underwent urethral reconstruction by using an autologous bladder mucosal graft. In 10 of these previous surgery for hypospadias or other penile anomalies had failed. Bladder mucosal graft was used in 2 cases for primary urethral reconstruction. Our results in using this method, mostly in hypospadias cripples, are satisfying, so that we are encouraged to use the autologous bladder mucosal graft for primary urethral reconstruction in selected cases with severe forms of hypospadias as well. PMID- 1892807 TI - SD-mice--an animal model for complex anorectal malformations. AB - Animal models for morphological investigations of anorectal malformations are barely known to pediatric surgeons. In this study the morphological characteristics of a spontaneous mutation of the house mouse, the so-called SD mouse, are described. The semidominant gene SD exerts its influence on the anorectum, the urogenital system and the axial skeleton. Many heterozygous (SD/+) and all homozygous (SD/SD) animals die shortly after birth due to their malformations. Surviving heterozygotes, identified by their short and deformed tails, may be used for breeding purposes. According to Mendel's laws, mating of such heterozygous yields 75% more or less malformed animals which may be used for morphological investigations. The morphological features of these animals were investigated in 61 neonatal SD-mice (33 SD/SD, 28 SD/+) and in 10 normal controls by microdissection and in 49 animals (25 SD/SD, 20 SD/+ and four normal controls) by serial sections. Of these, all homozygous and 10 heterozygous SD mice had anorectal malformations. The spectrum of these malformations is wide: very complex malformations in SD/SD mice and high anorectal malformations in SD/+ mice. These are comparable to morphological features found in humans and piglets. Hence the SD mouse represents an animal model for morphologic and embryonic investigations of complex anorectal malformations. PMID- 1892808 TI - Proline residues in transmembrane helices: structural or dynamic role? PMID- 1892809 TI - Contribution of the glutamine 19 side chain to transition-state stabilization in the oxyanion hole of papain. AB - The existence of an oxyanion hole in cysteine proteases able to stabilize a transition-state complex in a manner analogous to that found with serine proteases has been the object of controversy for many years. In papain, the side chain of Gln19 forms one of the hydrogen-bond donors in the putative oxyanion hole, and its contribution to transition-state stabilization has been evaluated by site-directed mutagenesis. Mutation of Gln19 to Ala caused a decrease in kcat/KM for hydrolysis of CBZ-Phe-Arg-MCA, which is 7700 M-1 s-1 in the mutant enzyme as compared to 464,000 M-1 s-1 in wild-type papain. With a Gln19Ser variant, the activity is even lower, with a kcat/KM value of 760 M-1 s-1. The 60- and 600-fold decreases in kcat/KM correspond to changes in free energy of catalysis of 2.4 and 3.8 kcal/mol for Gln19Ala and Gln19Ser, respectively. In both cases, the decrease in activity is in large part attributable to a decrease in kcat, while KM values are only slightly affected. These results indicate that the oxyanion hole is operational in the papain-catalyzed hydrolysis of CBZ-Phe Arg-MCA and constitute the first direct evidence of a mechanistic requirement for oxyanion stabilization in the transition state of reactions catalyzed by cysteine proteases. The equilibrium constants Ki for inhibition of the papain mutants by the aldehyde Ac-Phe-Gly-CHO have also been determined. Contrary to the results with the substrate, mutation at position 19 of papain has a very small effect on binding of the inhibitor.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1892810 TI - Engineering of papain: selective alteration of substrate specificity by site directed mutagenesis. AB - The S2 subsite specificity of the plant protease papain has been altered to resemble that of mammalian cathepsin B by site-directed mutagenesis. On the basis of amino acid sequence alignments for papain and cathepsin B, a double mutant (Val133Ala/Ser205Glu) was produced where Val133 and Ser205 are replaced by Ala and Glu, respectively, as well as a triple mutant (Val133Ala/Val157Gly/Ser205Glu), where Val157 is also replaced by Gly. Three synthetic substrates were used for the kinetic characterization of the mutants, as well as wild-type papain and cathepsin B: CBZ-Phe-Arg-MCA, CBZ-Arg-Arg-MCA, and CBZ-Cit-Arg-MCA. The ratio of kcat/KM obtained by using CBZ-Phe-Arg-MCA as substrate over that obtained with CBZ-Arg-Arg-MCA is 8.0 for the Val133Ala/Ser205Glu variant, while the equivalent values for wild-type papain and cathepsin B are 904 and 3.6, respectively. This change in specificity has been achieved by replacing only two amino acids out of a total of 212 in papain and with little loss in overall enzyme activity. However, further replacement of Val157 by Gly as in Val133Ala/Val157Gly/Ser205Glu causes an important decrease in activity, although the enzyme still displays a cathepsin B like substrate specificity. In addition, the pH dependence of activity for the Val133Ala/Ser205Glu variant compares well with that of cathepsin B. In particular, the activity toward CBZ-Arg-Arg-MCA is modulated by a group with a pKa of 5.51, a behavior that is also encountered in the case of cathepsin B but is absent with papain.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1892811 TI - Opposite facial specificity for two hydroquinone epoxidases: (3-si,4-re)-2,5 dihydroxyacetanilide epoxidase from Streptomyces LL-C10037 and (3-re,4-si)-2,5 dihydroxyacetanilide epoxidase from Streptomyces MPP 3051. AB - (3-si,4-re)-2,5-Dihydroxyacetanilide epoxidase (DHAE I), a key enzyme in the biosynthesis of the epoxysemiquinone antibiotic LL-C10037 alpha by Streptomyces LL-C10037 [Gould, S.J., & Shen, B. (1991) J. Am. Chem. Soc. 113, 684-686], and (3 re,4-si)-2,5-dihydroxyacetanilide epoxidase (DHAE II) isolated from Streptomyces MPP 3051--which yields the (3R,4S)-epoxyquinone mirror image product of DHAE I- are described. DHAE I was purified 640-fold. Gel permeation chromatography indicated an Mr of 117,000 +/- 10,000; SDS-PAGE gave a major band of 22,300 daltons, indicating that DHAE I is either a pentamer or hexamer in solution. The enzyme had a pH optimum of 6.5, a Km of 8.4 +/- 0.5 microM, and a Vmax of 3.7 +/- 0.2 mumol min-1 mg-1. DHAE II was purified 1489-fold. The enzyme was shown to be a dimer of Mr 33,000 +/- 2000, with 16,000-dalton subunits, with a pH optimum of 5.5 and a Km of 7.2 +/- 0.4 microM. Both enzymes required only O2 and substrate; flavin and nicotinamide coenzymes had little or no effect. Neither catalase nor EDTA affected the activity of either enzyme, but complete inhibition of both was obtained with 1,10-phenanthroline. The activity of the purified DHAE I could be enhanced, but only by Mn2+ (relative V = 246 at 0.04 mM), Ni2+ (relative V = 266 at 0.2 mM), or Co2+ (relative = 498 at 0.2 mM). Reconstitution from a DHAE I apoenzyme, generated by treatment with 1,10-phenanthroline followed by Sephadex G 25 chromatography, occurred only by addition of one of these three metals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1892812 TI - Effects of temperature on the fluorescence intensity and anisotropy decays of staphylococcal nuclease and the less stable nuclease-conA-SG28 mutant. AB - Frequency-domain fluorescence spectroscopy was used to investigate the effects of temperature on the intensity and anisotropy decays of the single tryptophan residues of Staphylococcal nuclease A and its nuclease-conA-SG28 mutant. This mutant has the beta-turn forming hexapeptide, Ser-Gly-Asn-Gly-Ser-Pro, substituted for the pentapeptide Tyr-Lys-Gly-Gln-Pro at positions 27-31. The intensity decays were analyzed in terms of a sum of exponentials and with Lorentzian distributions of decay times. The anisotropy decays were analyzed in terms of a sum of exponentials. Both the intensity and anisotropy decay parameters strongly depend on temperature near the thermal transitions of the proteins. Significant differences in the temperature stability of Staphylococcal nuclease and the mutant exist; these proteins show characteristic thermal transition temperatures (Tm) of 51 and 30 degrees C, respectively, at pH 7. The temperature dependence of the intensity decay data are shown to be consistent with a two-state unfolding model. For both proteins, the longer rotational correlation time, due to overall rotational diffusion, decreases dramatically at the transition temperature, and the amplitude of the shorter correlation time increases, indicating increased segmental motions of the single tryptophan residue. The mutant protein appears to have a slightly larger overall rotational correlation time and to show slightly more segmental motion of its Trp than is the case for the wild-type protein. PMID- 1892813 TI - Peroxidase-catalyzed S-oxygenation: mechanism of oxygen transfer for lactoperoxidase. AB - The mechanism of organosulfur oxygenation by peroxidases [lactoperoxidase (LPX), chloroperoxidase, thyroid peroxidase, and horseradish peroxidase] and hydrogen peroxide was investigated by use of para-substituted thiobenzamides and thioanisoles. The rate constants for thiobenzamide oxygenation by LPX/H2O2 were found to correlate with calculated vertical ionization potentials, suggesting rate-limiting single-electron transfer between LPX compound I and the organosulfur substrate. The incorporation of oxygen from 18O-labeled hydrogen peroxide, water, and molecular oxygen into sulfoxides during peroxidase-catalyzed S-oxygenation reactions was determined by LC- and GC-MS. All peroxidases tested catalyzed essentially quantitative oxygen transfer from 18O-labeled hydrogen peroxide into thiobenzamide S-oxide, suggesting that oxygen rebound from the oxoferryl heme is tightly coupled with the initial electron transfer in the active site. Experiments using H2(18)O2, 18O2, and H2(18)O showed that LPX catalyzed approximately 85, 22, and 0% 18O-incorporation into thioanisole sulfoxide oxygen, respectively. These results are consistent with a active site controlled mechanism in which the protein radical form of LPX compound I is an intermediate in LPX-mediated sulfoxidation reactions. PMID- 1892814 TI - Glycolysis and glucose uptake in intact outer segments isolated from bovine retinal rods. AB - Glucose transport across the plasma membrane of isolated bovine rod outer segments (ROS) was measured by uptake of 14C-labeled 3-O-methylglucose and 2 deoxyglucose and was inferred from deenergization of ROS with 2-deoxyglucose. Glucose transport was mediated by a facilitated diffusion glucose transporter that equilibrated external and internal free hexose concentrations. Glucose transport in ROS displayed two components as judged from kinetic analysis of hexose equilibration and as judged from inhibition by cytochalasin B and phloretin. Transport under exchange conditions was considerably faster as compared with net hexose uptake, similar to that observed for the erythrocyte glucose transporter. Sensitivity to cytochalasin B and affinity to 3-O methylglucose were similar to those observed for the hepatocyte glucose transporter. The cytochalasin-insensitive component appears unique to ROS and did not reflect leakage transport as judged from a comparison with L-glucose uptake. Glucose transport feeds glycolysis localized to ROS. We suggest that a major role for glycolysis in ROS is phosphorylation of GDP to GTP via pyruvate kinase and PEP, while phosphorylation of ADP to ATP can use the creatine kinase/phosphocreatine pathway as well. PMID- 1892815 TI - Structure and interactions of ether- and ester-linked phosphatidylethanolamines. AB - The ether-linked phospholipid 1,2-dihexadecylphosphatidylethanolamine (DHPE) was studied as a function of hydration and in fully hydrated mixed phospholipid systems with its ester-linked analogue 1,2-dipalmitoylphosphatidylethanolamine (DPPE). A combination of differential scanning calorimetry (DSC) and X-ray diffraction was used to examine the phase behavior of these lipids. By DSC, from 0 to 10 wt % H2O, DHPE displayed a single reversible transition that decreased from 95.2 to 78.8 degrees C and which was shown by X-ray diffraction data to be a direct bilayer gel to inverted hexagonal conversion, L beta----HII. Above 15% H2O, two reversible transitions were observed which stabilized at 67.1 and 92.3 degrees C above 19% H2O. X-ray diffraction data of fully hydrated DHPE confirmed the lower temperature transition to be a bilayer gel to bilayer liquid crystalline (L beta----L alpha) phase transition and the higher temperature transition to be a bilayer liquid-crystalline to inverted hexagonal (L alpha--- HII) phase transition. The lamellar repeat distance of gel-state DHPE increased as a function of hydration to a limiting value of 62.5 A at 19% H2O (8.6 mol of water/mol of DHPE), which corresponds to the hydration at which the transition temperatures are seen to stabilize by DSC. Electron density profiles of DHPE, in addition to calculations of the lipid layer thickness, confirmed that DHPE in the gel state forms a noninterdigitated bilayer at all hydrations. Fully hydrated mixed phospholipid systems of DHPE and DPPE exhibited two reversible transitions by DSC.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1892816 TI - DNA-induced increase in the alpha-helical content of C/EBP and GCN4. AB - Leucine zipper proteins comprise a recently identified class of DNA binding proteins that contain a bipartite structural motif consisting of a "leucine zipper" dimerization domain and a segment rich in basic residues responsible for DNA interaction. Protein fragments encompassing the zipper plus basic region domains (bZip) have previously been used to determine the conformational and dynamic properties of this motif. In the absence of DNA, the coiled-coil portion is alpha-helical and dimeric, whereas the basic region is flexible and partially disordered. Addition of DNA containing a specific recognition sequence induces a fully helical conformation in the basic regions of these fragments. However, the question remained whether the same conformational change would be observed in native bZip proteins where the basic regions might be stabilized in an alpha helical conformation even in the absence of DNA, through interactions with portions of the protein not included in the bZip motif. We have now examined the DNA-induced conformational transition for an intact bZip protein, GCN4, and for the bZip fragment of C/EBP with two enhancers that are differentially symmetric. Our results are consistent with the induced helical fork model wherein the basic regions are largely flexible in the absence of DNA and become fully helical in the presence of the specific DNA recognition sequence. PMID- 1892817 TI - Refolding and assembly of penicillin acylase, an enzyme composed of two polypeptide chains that result from proteolytic activation. AB - The in vitro folding and assembly of penicillin acylase (EC 3.5.1.11) (PA) to active enzyme has been studied. PA is a large bacterial protein (Mr = 86,000) comprising two peptides, alpha and beta, produced by proteolytic processing and activation of a 92-kDa precursor. Proteins that result from proteolytic processing are characteristically difficult if not impossible to refold. Different factors that affect folding and assembly of PA, including pH, ionic strength, and temperature, have been studied. Yields of 60% can be obtained, based on recovery of enzyme activity, together with another 20% of folded and associated monomer with conformation closely similar to that of the active enzyme but with the active site not formed. Evidence is presented for in vitro assembly proceeding via initial folding of the N-terminal alpha-peptide with subsequent collapse of the transiently folded beta-chain on to the surface of the former. A slow process of rearrangement follows association in vitro. Competition experiments support the proposal that the linker endopeptide in the precursor serves to increase the probability of productive collision between folded alpha- and beta-peptides. The effect of raised temperature is to interfere with the folding of the alpha-peptide, thus preventing proper folding of the precursor. This finding accounts for the basis of the temperature regulation of PA production in vivo. PMID- 1892818 TI - A 1H NMR probe for mobility in the reactive center loops of serpins: spin-echo studies of native and modified forms of ovalbumin and alpha 1-proteinase inhibitor. AB - It has recently been proposed that the expression of inhibitory activity in serine protease inhibitors (serpins) is a function of the mobility of the extended alpha-helical reactive center loop [Stein, P.E., Leslie, A.G.W., Finch, J.T., Turnell, W.G., McLaughlin, P.J., & Carrell, R.W. (1990) Nature 347, 99 102]. We have employed solution 1H NMR methods, including the Carr-Purcell Meiboom-Gill (CPMG) and Hahn spin-echo pulse sequences, to try to identify such regions by virtue of their anticipated longer T2 relaxation times in two of the best characterized members of the serpin superfamily, ovalbumin and alpha 1 proteinase inhibitor. The CPMG spectra of native ovalbumin reveal the presence of long-lived resonances from the methyl protons of alanine residues and the CH3 protons of leucine or valine residues as well as the acetyl and ring methine protons of the carbohydrate moieties. Following reaction of ovalbumin with subtilisin Carlsberg to generate plakalbumin [where excision from within the reactive center loop homologue of a hexa- or heptapeptide, with sequence (E)-A-G V-D-A-A, occurs], its CPMG spectrum retained almost all of the originally present long-lived resonances. Concurrent with the retention of these mobile resonances in plakalbumin is the appearance of two additional resonances consistent with the formation of new C and N termini. On the basis of the proposed mobility of the reactive center loop, it had been expected that removal of the alanine-rich hexapeptide would result in loss of some or all of the long-lived alanine methyl resonances.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1892819 TI - Thermodynamics of condensation of nuclear chromatin. A differential scanning calorimetry study of the salt-dependent structural transitions. AB - We present a detailed thermodynamic investigation of the conformational transitions of chromatin in calf thymus nuclei. Differential scanning calorimetry was used as the leading method, in combination with infrared spectroscopy, electron microscopy, and techniques for the molecular characterization of chromatin components. The conformational transitions were induced by changes in the counterion concentration. In this way, it was possible to discriminate between the interactions responsible for the folding of the higher order structure and for the coiling of nucleosomal DNA. Our experiments confirm that the denaturation of nuclear chromatin at physiological ionic strength occurs at the level of discrete structural domains, the linker and the core particle, and we were able to rule out that the actual denaturation pattern might be determined by dissociation of the nucleohistone complex and successive migration of free histones toward native regions, as recently suggested. The sequence of the denaturation events is (1) the conformational change of the histone complement at 66 degrees C, (2) the unstacking of the linker DNA at 74 degrees C, and (3) the unstacking of the core particle DNA, that can be observed either at 90 or at 107 degrees C, depending on the degree of condensation of chromatin. Nuclear chromatin unfolds in low-salt buffers, and can be refolded by increasing the ionic strength, in accordance with the well-known behavior of short fragments. The process is athermal, therefore showing that the stability of the higher order structure depends on electrostatic interactions. The transition between the folded conformation and the unfolded one proceeds through an intermediate condensation state, revealed by an endotherm at 101 degrees C. The analysis of the thermodynamic parameters of denaturation of the polynucleosomal chain demonstrates that the wrapping of the DNA around the histone octamer involves a large energy change. The most striking observation concerns the linker segment, which melts a few degrees below the peak temperature of naked DNA. This finding is in line with previous thermal denaturation investigations on isolated chromatin at low ionic strength, and suggests that a progressive destabilization of the linker occurs in the course of the salt-induced coiling of DNA in the nucleosome. PMID- 1892820 TI - Heparin prevents the binding of phospholipase A2 to phospholipid micelles: importance of the amino-terminus. AB - The activity of the major isoform of porcine pancreatic phospholipase A2 (PLA2), designated B-PLA2, against micellar substrates is inhibited by heparin. Inhibition is a consequence of binding of the enzyme to heparin, documented by a heparin-induced alteration in the intrinsic fluorescence of B-PLA2 and in the 8 anilino-1-naphthalene sulfonate fluorescence and by the enhanced rate of chemical modification of the active site residue His-48. As a consequence of heparin binding, the conformation of B-PLA2 at the active site and at the amino-terminus is altered, and the enzyme does not bind to phospholipid micelles. In spite of the heparin-induced conformational changes, B-PLA2 retains its ability to catalyze the hydrolysis of monomeric phospholipid. Other glycosaminoglycans can bind to and inhibit the activity of B-PLA2 toward organized phospholipids, but none tested is as effective as heparin. An isoform of the pancreatic enzyme, designated UB-PLA2 and which corresponds to iso-pig PLA2, does not bind to nor is its catalytic activity influenced by heparin. A peptide corresponding to the amino-terminal 26 residues of B-PLA2 can rescue PLA2 from heparin inhibition. A similar peptide corresponding to the amino-terminus of UB-PLA2 has no effect on heparin inhibition. A model for the inhibition of B-PLA2 by heparin is proposed in which the catalytically significant effect of heparin is to interact directly with the amino-terminus of B-PLA2, the interfacial recognition site, to prevent the enzyme from binding to micellar substrates. PMID- 1892821 TI - Study of QB- stabilization in herbicide-resistant mutants from the purple bacterium Rhodopseudomonas viridis. AB - The pH dependences of the rate constants of P+QB- (kBP) and P+QA- (kAP) charge recombination decays have been studied by flash-induced absorbance change technique, in chromatophores of three herbicide-resistant mutants from Rhodopseudomonas (Rps.) viridis, and compared to the wild type. P, QA, and QB are the primary electron donor and the primary and the secondary quinone acceptors, respectively. The triazine resistant mutants T1 (Arg L217----His and Ser L223--- Ala), T3 (Phe L216----Ser and Val M263----Phe), and T4 (Tyr L222----Phe), all mutated in the QB binding pocket of the reaction center, have previously been characterized (Sinning, I., Michel, H., Mathis, P., & Rutherford, A. W. (1989) Biochemistry 28, 5544-5553). The pH dependence curves of kBP in T4 and the wild type are very close. This confirms that the sensitivity toward DCMU of T4 is mainly due to a structural rearrangement in the QB pocket rather than to a change in the charge distribution in this part of the protein. In T3, a 6-fold increase of kAP is observed (kAP = 4200 +/- 300 s-1 at pH 8) compared to that of the wild type (kAP = 720 +/- 50 s-1 at pH 8). We propose that the Val M263----Phe mutation induces a free energy decrease between P+QA- and P+I- (delta G zero IA) (I is the primary electron acceptor) of about 49 meV. The very different pH dependence of kAP in T3 suggests a substantial change in the QA pocket. The 2.5 times increase of kAP above pH 9.5 in the wild type is no longer detected in T3.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1892822 TI - Structural differences in solution and crystalline forms of met-myoglobin. AB - For several decades X-ray diffraction studies have been the paragon of biological structure studies at atomic resolution. Diffraction provides three-dimensional structure information, which is essential to our fundamental understanding of protein function. However, since X-ray diffraction cannot be done to atomic resolution on proteins in their native solution or membrane-bound state, the possibility exists that the conformations of the protein in crystals are slightly different from the conformations in solution, and attempts to interpret details of the structure may be misleading and without physiological relevance. In this paper, we show that this concern is justified for a familiar protein, myoglobin. Performing X-ray absorption fine structure experiments on both solution and crystalline met-myoglobin (met-Mb), we find significant differences in the local environment of the iron between the two states. Specifically, the average iron nearest neighbor atom distance in the crystalline form is 0.05 A shorter than that in the solution form, and the iron-nearest neighbor bond is more rigid in the crystalline met-Mb. Possible artifactual explanations for the differences have been ruled out. PMID- 1892823 TI - Two distinct subunits of hemerythrin from the brachiopod Lingula reevii: an apparent requirement for cooperativity in O2 binding. AB - Reported are results on the subunit composition of octameric hemerythrin (Hr) from the brachiopod Lingula reevii. Unlike most other Hrs, L. reevii Hr shows cooperativity in O2 binding. Purified L. reevii Hr was found to consist of two different subunits in approximately equimolar proportions. These two subunits differ in molecular weight by approximately 1000. Amino acid sequence data for the first 24 residues of the two subunits, labeled alpha and beta, show 70% identity with each other. Comparisons to amino acid sequences of other Hrs show approximately 50% identity in the first 24 residues and that both the alpha and beta subunits of L. reevii Hr have one residue deleted at their amino termini. Very recently, one other Hr, that from the brachiopod Lingula unguis, was also shown to contain equimolar proportions of two different subunits [Satake, K., Yugi, M., Kamo, M., Kihara, H., & Tsugita, A. (1990) Protein Seq. Data Anal. 3, 1 5], and this Hr also shows cooperativity in O2 binding. An alpha 4 beta 4 octamer is, therefore, proposed to be a common feature of those Hrs that show such cooperativity. Likely arrangements of alpha and beta subunits within an alpha 4 beta 4 octamer having the same configuration of subunits as that in other octameric Hrs are proposed. The most probable arrangements can be readily derived from physically reasonable restrictions on the types of intersubunit interactions and on transmission of allosteric effects. PMID- 1892824 TI - Effects of Asp-96----Asn, Asp-85----Asn, and Arg-82----Gln single-site substitutions on the photocycle of bacteriorhodopsin. AB - Bacteriorhodopsin (BR) with the single-site substitutions Arg-82----Gln (R82Q), Asp-85----Asn (D85N), and Asp-96----Asn (D96N) is studied with time-resolved absorption spectroscopy in the time regime from nanoseconds to seconds. Time resolved spectra are analyzed globally by using multiexponential fitting of the data at multiple wavelengths and times. The photocycle kinetics for BR purified from each mutant are determined for micellar solutions in two detergents, nonyl glucoside and CHAPSO, and are compared to results from studies on delipidated BR (d-BR) in the same detergents. D85N has a red-shifted ground-state absorption spectrum, and the formation of an M intermediate is not observed. R82Q undergoes a pH-dependent transition between a purple and a blue form with different pKa values in the two detergents. The blue form has a photocycle resembling that for D85N, while the purple form of R82Q forms an M intermediate that decays more rapidly than in d-BR. The purple form of R82Q does not light-adapt to the same extent as d-BR, and the spectral changes in the photocycle suggest that the light adapted purple form of R82Q contains all-trans- and 13-cis-retinal in approximately equal proportions. These results are consistent with the suggestions of others for the roles of Arg-82 and Asp-85 in the photocycle of BR, but results for D96N suggest a more complex role for Asp-96 than previously suggested. In nonyl glucoside, the apparent decay of the M-intermediate is slower in D96N than in d-BR, and the M decay shows biphasic kinetics. However, the role of Asp-96 is not limited to the later steps of the photocycle. In D96N, the decay of the KL intermediate is accelerated, and the rise of the M intermediate has an additional slow phase not observed in the kinetics of d-BR. The results suggest that Asp-96 may play a role in regulating the structure of BR and how it changes during the photocycle. PMID- 1892825 TI - Olfactomedin: purification, characterization, and localization of a novel olfactory glycoprotein. AB - We have identified a novel glycoprotein expressed exclusively in frog olfactory neuroepithelium, which we have named "olfactomedin". Olfactomedin is a 57-kDa glycoprotein recognized by seven monoclonal antibodies, previously shown to react solely with proteins of olfactory cilia preparations. It undergoes posttranslational modifications, including dimerization via intermolecular disulfides and attachment of complex carbohydrate moieties that contain N acetylglucosamine and beta-D-galactoside sugars. Olfactomedin strongly binds to Ricinus communis agglutinin I and has been purified to homogeneity by lectin affinity chromatography. Polyclonal rabbit antiserum raised against purified olfactomedin confirmed that it is expressed only in olfactory tissue. Immunohistochemical studies at the light microscopic and electron microscopic level show that olfactomedin is localized in secretory granules of sustentacular cells, in acinar cells of olfactory glands, and at the mucociliary surface. The massive production of olfactomedin and its striking deposition at the chemosensory surface of the olfactory neuroepithelium suggest a role for this protein in chemoreception. PMID- 1892826 TI - Structural conservation in parallel beta/alpha-barrel enzymes that catalyze three sequential reactions in the pathway of tryptophan biosynthesis. AB - Three successive steps in tryptophan biosynthesis are catalyzed by single-domain proteins, each folded as a parallel beta/alpha-barrel, as observed in the crystal structures of the bienzyme (phosphoribosyl)-anthranilate isomerase:indoleglycerolphosphate synthase from Escherichia coli [Priestle, J.P., Grutter, M. G., White, J. L., Vincent, M. G., Kania, M., Wilson, E., Jardetzky, T. S., Kirschner, K., & Jansonius, J. N. (1987) Proc. Natl. Acad. Sci. U.S.A. 84, 5690-5694] and the alpha-subunit of the tetrameric bienzyme tryptophan synthase from Salmonella typhimurium [Hyde, C. C., Ahmed, S. A., Padlan, E. A., Miles, E. W., & Davies, D. R. (1988) J. Biol. Chem. 263, 17857-17871]. Recent refinement of the crystal structures of these enzymes at atomic resolution revealed that they contain a common phosphate group binding site in the beta/alpha-barrel, created by residues of the loop between beta-strand 7 and alpha-helix 7 and the N terminus of an additional helix 8'. The close similarities of their beta/alpha barrel structures permitted the alignment of 50-75% of their respective amino acid sequences. Considerable sequence similarity was detected in the regions spanning the phosphate binding sites, whereas the percentage of identical residues was barely significant for the remaining parts of the enzymes. These observations suggest divergent evolution of these three beta/alpha-barrel enzymes involved in tryptophan biosynthesis. The same phosphate binding site was also observed in six other beta/alpha-barrel enzymes that are functionally unrelated to those involved in tryptophan biosynthesis: triosephosphate isomerase, ribulose 1,5-bisphosphate carboxylase/oxygenase, glycolate oxidase, flavocytochrome b2, trimethylamine dehydrogenase, and tentatively also fructosebisphosphate aldolase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1892827 TI - Self and foreign peptides interact with intact and disassembled MHC class II antigen HLA-DR via tryptophan pockets. AB - The acid release of endogenous peptides from immunoaffinity-pure human major histocompatibility complex (MHC) class II proteins HLA-DR1 is accompanied by an 18% decrease in intrinsic tryptophan fluorescence. The effect is totally reversible upon readdition of an autologous endogenous peptide fraction. High performance size-exclusion chromatographic (HPSEC) binding and release studies with a nonfluorescent HLA-DR1-restricted influenza matrix peptide IM(18-29) prove the fact that Trp residues of the HLA protein change their fluorescence intensities. Since the far-UV circular dichroism spectra of HLA molecules before and after peptide release, DR1[NAT] and DR1[REL], show very small differences, we can rule out the breakdown of secondary structural elements under release conditions, although DR[REL] consists of disassembled alpha- and beta-subunits, as evidenced by HPSEC. Quenching of DR1[NAT] and DR1[REL] using the neutral quencher acrylamide results in a 20% increase in total accessibility of the nine residue Trp population whereas quenching by iodide yields only a 5% increase. Both results taken together tell us that two Trp residues, preferentially ones located in apolar pockets, become accessible upon the release of peptides. The significantly smaller fluorescence enhancement upon binding IM(18-29) of DR3[REL], exclusively lacking Trp-9(beta 1), and the missing tendency to reassemble under the influence of IM(18-29) compared to DR1[REL] suggest an important role for position 9(beta 1). The region around Trp-43(alpha 1) should be responsible for the binding of IM(18-29) to the alpha-subunits of DR1 and DR3, respectively, as verified by fluorometric HPSEC and SDS-PAGE. Obviously, our findings are in total agreement with the hypothetical MHC class II model, whereafter Trp-9(beta 1) and Trp-43(alpha 1) besides Trp-61(beta 1) are constituents of the binding groove of DR1. Extending the homology to MHC class I products, we postulate the existence of three hydrophobic pockets in the binding site of DR1 with the cited Trp residues being juxtaposed to contacting apolar peptide side chains in HLA-peptide complexes. According to the deduced two residue-contact model the minimal consensus motif for DR1-restricted peptide antigens consists of two hydrophobic residues lying 14-16 A apart in the bound state of the peptide. PMID- 1892828 TI - Solution conformational preferences of immunogenic peptides derived from the principal neutralizing determinant of the HIV-1 envelope glycoprotein gp120. AB - With standard one- and two-dimensional proton NMR techniques, a common structural motif has been identified in water solutions of short peptide sequences derived from the envelope glycoprotein gp120 of HIV-1. Three peptides of lengths 12, 24, and 40 residues (termed RP342, RP142, and RP70, respectively) were synthesized, each containing a central amino acid sequence common to many HIV-1 isolates. In addition, RP70 contained a disulfide bond between cysteine residues close to the ends of the molecule, forming a loop that is thought to constitute an important structural and immunological component of the intact glycoprotein. Peptides RP70 and RP142 showed evidence for the presence of a significant population of conformations containing a beta-turn in the conserved sequence Gly-Pro-Gly-Arg. Strong nuclear Overhauser effect (NOE) connectivities were observed between the amide protons of the arginine and the adjacent glycine. A weak NOE connectivity was observed between the C alpha H of the proline residue and the NH of the Arg [a d alpha N(i,i + 2) NOE connectivity], confirming the presence of a conformational preference for a turn conformation in this sequence. The remainder of the peptide showed evidence of conformational averaging: no NMR evidence for a uniquely folded structure was obtained for any of the peptides in water solution. Circular dichroism (CD) spectra indicated that no ordered helix was present in water solutions of RP70, although a CD spectrum that indicated the presence of approximately 30% helix could be induced by the addition of trifluoroethanol.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1892829 TI - Characterization of the tryptophan-derived quinone cofactor of methylamine dehydrogenase by resonance Raman spectroscopy. AB - The resonance Raman (RR) spectrum of oxidized methylamine dehydrogenase (MADHOX) exhibits a set of C-H, C-C, C = C, and C = O vibrational modes between 900 and 1700 cm-1 that are characteristic of the quinone moiety of the tryptophan tryptophlyquinone (TTQ) cofactor. The close similarity of the RR spectra for MADHs from Paracoccus denitrificans (Pd), Thiobacillus versutus (Tv), and bacterium W3A1 proves that the same cofactor is present in all three proteins. The MADHs from Pd and Tv have a v(C = O) mode at approximately 1625 cm-1 that shifts approximately 20 cm-1 upon 18O substitution of one of the carbonyl oxygens and is assigned to the in-phase symmetric stretch of the two C = O groups. The semiquinone form of Pd MADH has its own characteristic RR spectrum with altered peak frequencies and intensities as well as a decrease in the total number of peaks. The hydroxide and ammonia adducts of MADHOX produce RR spectra similar to that of the semiquinone. The spectral changes in all three cases are interpreted as being due to reduced conjugation of the cofactor. The ammonia adduct is formulated as a carbinolamine, a likely intermediate in the enzymatic mechanism. In contrast, formation of the electron-transfer complex between amicyanin and MADHOX has no effect on the vibrational frequencies (and, hence, structure) of either the MADH quinone or the amicyanin blue copper site. The behavior of the TTQ cofactors of Pd and Tv MADHs are very similar to one another and somewhat different from W3A1 MADH, particularly with regard to adduct formation and ability to undergo isotope exchange with solvent. These differences are ascribed to the cofactor environments within the proteins rather than to the structure of the cofactor itself. PMID- 1892830 TI - Deuterium NMR investigation of backbone dynamics in the synthetic oligonucleotide [d(CGCGAATTCGCG)]2. AB - Backbone dynamics in the [5',5"-2H2]2'-deoxythymidine labeled duplex dodecamer [d (CGCGAAT*T*CGC)]2 have been investigated by solid-state 2H NMR. Quadrupolar echo line shapes, spin-lattice relaxation, and quadrupolar echo decay times were obtained over hydration levels ranging from W = 0.0 to 25.2 (moles of H2O/mole of nucleotide). Variation of the line shape with changing hydration level was analyzed by using models employed in previous investigations of dodecamer base and sugar dynamics. Both fast local motions and a slower helix motion were present within the oligonucleotide. The fast motion was modeled as a four-site libration whose amplitude increased with hydration level. The root mean square amplitude of this librational model was 2-6 degrees larger than the amplitude observed in either the furanose ring or base labeled material for the entire range of hydration levels investigated. The observed line shape was inconsistent with a rapid three-site trans-gauche isomerization. A slow motion about the helix axis was observed at low water levels and increased in rate and amplitude with hydration. This motional model is in agreement with previous oligonucleotide studies. PMID- 1892831 TI - Heat-induced DNA cleavage by esperamicin antitumor antibiotics. AB - Esperamicin A1 effectively breaks DNA strands upon heating at 50 degrees C. The preferential DNA cutting sites of heat-activated esperamicin A1 are random and clearly differ from those of thiol- or UV-light-mediated DNA breakage with esperamicin A1. The absence of heat-induced DNA cleavage by esperamicin Z and the induction of the DNA breakage by esperamicin A1 disulfide indicate that (1) the enediyne core plays a significant role in this DNA strand scission and (2) the DNA cutting with the heat-activated esperamicin antibiotics does not necessarily require a trisulfide trigger in the aglycon portion. On the basis of the present results, a probable mechanism for the heat-induced DNA cleavage of esperamicin A1 has been proposed. PMID- 1892832 TI - Binding of triple helix forming oligonucleotides to sites in gene promoters. AB - A class of triplex-forming oligodeoxyribonucleotides (TFOs) is described that can bind to naturally occurring sites in duplex DNA at physiological pH in the presence of magnesium. The data are consistent with a structure in which the TFO binds in the major groove of double-stranded DNA to form a three-stranded complex that is superficially similar to previously described triplexes. The distinguishing features of this class of triplex are that TFO binding apparently involves the formation of hydrogen-bonded G.GC and T.AT triplets and the TFO is bound antiparallel with respect to the more purine-rich strand of the underlying duplex. Triplex formation is described for targets in the promoter regions of three different genes: the human c-myc and epidermal growth factor receptor genes and the mouse insulin receptor gene. All three sites are relatively GC rich and have a high percentage of purine residues on one strand. DNase I footprinting shows that individual TFOs bind selectively to their target sites at pH 7.4-7.8 in the presence of millimolar concentrations of magnesium. Electrophoretic analysis of triplex formation indicates that specific TFOs bind to their target sites with apparent dissociation constants in the 10(-7)-10(-9) M range. Strand orientation of the bound TFOs was confirmed by attaching eosin or an iron chelating group to one end of the TFO and monitoring the pattern of damage to the bound duplex DNA. Possible hydrogen-bonding patterns and triplex structures are discussed. PMID- 1892833 TI - Mechanism of the reaction catalyzed by mandelate racemase. 1. Chemical and kinetic evidence for a two-base mechanism. AB - The fate of the alpha-hydrogen of mandelate in the reaction catalyzed by mandelate racemase has been investigated by a mass spectroscopic method. The method entails the incubation of (R)- or (S)-[alpha-1H]mandelate in buffered D2O to a low extent of turnover (about 5-8%), esterification of the resulting mixture of mandelates with diazomethane, derivatization of the methyl esters with a chiral derivatizing agent, and quantitation of the isotope content of the alpha hydrogen of both substrate and product by gas chromatography/mass spectrometric analysis. No significant substrate-derived alpha-protium was found in the product for racemization in either direction. In addition, in the (R) to (S) direction almost no exchange (less than or equal to 0.4%) of the alpha-hydrogen in the remaining (R) substrate pool occurred, but in the (S) to (R) direction 3.5-5.1% exchange of the alpha-hydrogen in the remaining substrate (after 5.1-7.2% net turnover) was found. Qualitatively similar results were obtained in the (S) to (R) direction in H2O when (S)-[alpha-2H]mandelate was used as substrate. In other experiments, an overshoot in the progress curve was observed when the racemization of either enantiomer of [alpha-1H]mandelate in D2O was monitored by following the change in ellipticity of the reaction mixture; the magnitude of the overshoot was greater in the (R) to (S) than in the (S) to (R) direction. All of the available data indicate that the reaction catalyzed by mandelate racemase proceeds by a two-base mechanism, in contrast to earlier proposals. PMID- 1892834 TI - Mechanism of the reaction catalyzed by mandelate racemase. 2. Crystal structure of mandelate racemase at 2.5-A resolution: identification of the active site and possible catalytic residues. AB - The crystal structure of mandelate racemase (MR) has been solved at 3.0-A resolution by multiple isomorphous replacement and subsequently refined against X ray diffraction data to 2.5-A resolution by use of both molecular dynamics refinement (XPLOR) and restrained least-squares refinement (PROLSQ). The current crystallographic R-factor for this structure is 18.3%. MR is composed of two major structural domains and a third, smaller, C-terminal domain. The N-terminal domain has an alpha + beta topology consisting of a three-stranded antiparallel beta-sheet followed by an antiparallel four alpha-helix bundle. The central domain is a singly wound parallel alpha/beta-barrel composed of eight central strands of beta-sheet and seven alpha-helices. The C-terminal domain consists of an irregular L-shaped loop with several short sections of antiparallel beta-sheet and two short alpha-helices. This C-terminal domain partially covers the junction between the major domains and occupies a region of the central domain that is filled by an eight alpha-helix in all other known parallel alpha/beta-barrels except for the barrel domain in muconate lactonizing enzyme (MLE) [Goldman, A., Ollis, D. L., & Steitz, T. A. (1987) J. Mol. Biol. 194, 143] whose overall polypeptide fold and amino acid sequence are strikingly similar to those of MR [Neidhart, D. J., Kenyon, G. L., Gerlt, J. A., & Petsko, G. A. (1990) Nature 347, 692]. In addition, the crystal structure reveals that, like MLE, MR is tightly packed as an octamer of identical subunits. The active site of MR is located between the two major domains, at the C-terminal ends of the beta-strands in the alpha/beta-barrel domain. The catalytically essential divalent metal ion is ligated by three side-chain carboxyl groups contributed by residues of the central beta-sheet. A model of a productive substrate complex of MR has been constructed on the basis of difference Fourier analysis at 3.5-A resolution of a complex between MR and (R,S)-p-iodomandelate, permitting identification of residues that may participate in substrate binding and catalysis. The ionizable groups of both Lys 166 and His 297 are positioned to interact with the chiral center of substrate, suggesting that both of these residues may function as acid/base catalysts.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1892835 TI - Conformational stability of pig citrate synthase and some active-site mutants. AB - The conformational stabilities of native pig citrate synthase (PCS), a recombinant wild-type PCS, and six active-site mutant pig citrate synthases were studied in thermal denaturation experiments by circular dichroism and in urea denaturation experiments by using DTNB to measure the appearance of latent SH groups. His274 and Asp375 are conserved active-site residues in pig citrate synthase that bind to substrates and are implicated in the catalytic mechanism of the enzyme. By site-directed mutagenesis, His274 was replaced with Gly and Arg, while Asp375 was replaced with Gly, Asn, Glu, or Gln. These modifications were previously shown to result in 10(3)-10(4)-fold reductions in enzyme specific activities. The thermal unfolding of pig citrate synthase and the six mutants in the presence and absence of substrates showed large differences in the thermal stabilities of mutant proteins compared to the wild-type pig citrate synthase. The functions of His274 and Asp375 in ligand binding were measured by oxalacetate protection against urea denaturation. These data indicate that active-site mutations that decrease the specific activity of pig citrate synthase also cause an increase in the conformational stability of the protein. These results suggest that specific electrostatic interactions in the active site of citrate synthase are important in the catalytic mechanism in the chemical transformations as well as the conformational flexibility of the protein, both of which are important for the overall catalytic efficiency of the enzyme. PMID- 1892836 TI - Inhibition of substrate binding to the adrenal cytochrome P450C-21 by acrylamide and its implications for solvent accessibility of the binding site in the microsomes. AB - The present study offers evidence indicating that acrylamide, a highly polar molecule and an efficient quencher of tryptophanyl fluorescence, inhibits substrate binding to P450C-21 in bovine adrenocortical microsomes, in a competitive manner similar to that in the purified enzyme. Resolution of the fluorescence-quenching data revealed an acrylamide quenching constant (K2 = 9.9 M, that is, the association constant for the quencher-fluorophore complex) that was similar to the reciprocal of its inhibition constant (1/Ki = Ka = 8.3 +/- 0.9 M) for substrate binding. The substrate inhibited the fluorescence quenching by acrylamide as indicated by its concentration-dependent decrease in K2. The inhibition was in accordance with partial competition. These results are essentially similar to those previously observed in the purified lipid-free enzyme. In addition, the substrate dissociation, acrylamide inhibition, and fluorescence-quenching constants and the tryptophanyl fluorescence maximum (340 342 nm) were essentially the same in the microsomes and the lipid-free purified enzyme. These results indicate that the substrate-binding site of P450C-21 and the concerned tryptophan are accessible to the highly polar molecule in the microsomal membranes, similar to that in the lipid-free purified enzyme. This implies that the substrate-binding site is not shielded by lipids in such a way that only the substrate in the lipid phase can gain access to the binding site. This conclusion is consistent with the currently favored model, for membrane topology of mammalian P450 enzymes, in which P450 is anchored to the membrane through a short N-terminal sequence while the remaining portion of the molecule is exposed to polar environment. PMID- 1892837 TI - Site-specific phosphorylation by protein kinase C inhibits assembly-promoting activity of microtubule-associated protein 4. AB - We have examined the phosphorylation of bovine microtubule-associated protein 4 (MAP4), formerly named MAP-U, by protein kinase C (PKC). When MAP4 was incubated with PKC, about 1 mol of phosphate was incorporated/mol of MAP4. Phosphorylation of MAP4 caused a remarkable decrease in the ability of the MAP to stimulate microtubule assembly. MAP4 consists of an amino-terminal projection domain and a carboxyl-terminal microtubule-binding domain. The carboxyl-terminal domain is subdivided into a Pro-rich region and an assembly-promoting (AP) sequence region containing four tandem repeats of AP sequence that is conserved in MAP4, MAP2, and tau [Aizawa et al. (1990) J. Biol. Chem. 265, 13849-13855]. In order to identify the site of MAP4 phosphorylated by PKC, a series of expressed MAP4 fragments was prepared and treated with the kinase. A fragment corresponding to the Pro-rich region (P fragment) was phosphorylated, while fragments corresponding to the projection domain and the AP sequence region were not. In addition, chymotryptic digestion of an authentic MAP4 prephosphorylated by PKC revealed that phosphate was incorporated almost exclusively into a 27-kDa fragment containing the carboxyl-terminal half of the Pro-rich region. We investigated the phosphorylation site in MAP4 using the P fragment and found that Ser815 was phosphorylated almost exclusively. We conclude that the phosphorylation of a single Ser residue in the Pro-rich region negatively regulates the assembly-promoting activity of MAP4. PMID- 1892838 TI - alpha-Conotoxins, small peptide probes of nicotinic acetylcholine receptors. AB - alpha-Conotoxins, a family of small peptides from the venoms of the Conus marine moluscs, are selective, snake alpha-neurotoxin-competitive antagonists of the nicotinic acetylcholine receptor. A new alpha-conotoxin, SIA, has been purified, sequenced, and synthesized. Cross-linking with bivalent reagents and photoaffinity labeling of the acetylcholine receptor with alpha-conotoxin yield covalent adducts. Surprisingly, cross-linking to other subunits is considerably more efficient than to the alpha subunit. The relative efficiency of photoactivatable cross-linking to different subunits of the receptor is a function of placement of the photoactivatable group on the toxin. Since the structures of alpha-conotoxins can be solved by 2D NMR [see Pardi et al. (1989) Biochemistry 28, 5494-5508; Kobayashi et al. (1989) Biochemistry 28, 4853-4860], this family of toxins should provide a set of new ligands for probing the acetylcholine receptor with considerable precision. PMID- 1892839 TI - 1H NMR and circular dichroism studies of the N-terminal domain of cyclic GMP dependent protein kinase: a leucine/isoleucine zipper. AB - Cyclic GMP dependent protein kinase exists as a dimer in its native form. A peptide corresponding to the dimerization domain in the N-terminal segment has been characterized by circular dichroism, ultracentrifugation, and 1H NMR spectroscopy. The peptide (G-kinase1-39 amide) is shown to be dimeric in solution. Determination of the molecular weight of the species in solution from the sedimentation coefficient and diffusion coefficient yields a value more than twice that of the monomeric species. Circular dichroism studies show G-kinase1-39 amide to be largely helical in aqueous solution and stable over a wide range of pH and temperature. The conformational stability is found to be concentration dependent, the peptide having a melting temperature of 75 degrees C (at 20 microM and pH 4.0). The assignment of the 1H NMR spectrum and analysis of the patterns of nuclear Overhauser enhancements confirm the helical nature of the conformation. Distance geometry calculations result in a well-defined helical structure containing a kink near Ser 26. The dimerization of G-kinase is most likely to occur through the hydrophobic interaction of leucine and isoleucine side chains located on one face of a helical structure with supporting electrostatic interactions between flanking side chains. The dimerization domain of G-kinase is clearly analogous to the "leucine zipper" motifs found in a number of DNA transcriptional activators. PMID- 1892840 TI - Alternating zinc fingers in the human male-associated protein ZFY: HX3H and HX4H motifs encode a local structural switch. AB - The two-finger repeat in the human male-associated protein ZFY provides a model for comparative 2D-NMR studies of classical and variant Zn fingers. This repeat is defined in part by an alternation in spacing between consensus (HX3H) and variant (HX4H) histidine spacings. To investigate the effects of a "switch" between alternative histidine spacings, we have designed an HX3H analogue of a representative HX4H domain of known structure [ZFY-6; Kochoyan, M., Havel, T., Nguyen, D. T., Dahl, C. E., Keutmann, H. T., & Weiss, M. A. (1991) Biochemistry 30, 3371-3386]. The HX3H analogue (designated ZFY-switch) forms a tetrahedral Co2+ complex whose thermodynamic stability is similar to that of the parent peptide. 2D-NMR studies demonstrate that ZFY-switch and ZFY-6, although similar in overall structure, exhibit significant local changes near the site of deletion. Whereas the HX4H site in the native finger forms a nonstandard loop, the HX3H site in ZFY-switch folds as a 3(10) extension of the C-terminal alpha helix, as observed in the NMR solution structure of a consensus HX3H domain [Lee, M. S., Gippert, G. P., Soman, K. V., Case, D. A., & Wright, P. E. (1989) Science 245, 635-637] and in the crystal structure of a representative Zn finger-DNA complex [Pavletich, N. P., & Pabo, C. O. (1991) Science 252, 809-817]. We propose that variant histidine spacings (HX3H and HX4H) encode a local switch between alternative surface architectures with implications for models of protein-DNA recognition. PMID- 1892841 TI - Structure of the detergent phase and protein-detergent interactions in crystals of the wild-type (strain Y) Rhodobacter sphaeroides photochemical reaction center. AB - Rhodobacter sphaeroides (strain Y) reaction center (RC) crystals were grown in the presence of n-octyl beta-glucoside (beta-OG). In order to determine the structure of the detergent phase in these crystals, low-resolution neutron diffraction experiments were performed at different contrasts obtained by varying the H2O/D2O ratio in the solvent. From the contrast variation data and from the RC atomic coordinates determined by X-ray diffraction [Arnoux, B., Ducruix, A., Reiss-Husson, F., Lutz, M., Norris, J., Schiffer, M., & Chang, C. H. (1989) FEBS Lett. 258, 47-50], a model was obtained for the structure of the detergent phase in the crystal. The detergent forms a ring-shaped micelle surrounding the most hydrophobic part of the transmembrane alpha helices of the RC. Each detergent ring is connected to two next-neighbor rings by intermicellar bridges. The detergent phase is organized thus in infinite zigzag chains parallel to the b axis of the P2(1)2(1)2(1) unit cell. The main interactions between beta-OG molecules and the RC molecules are hydrophobic and are localized at the level of the transmembrane alpha helices. This interaction replaces the phospholipid protein interaction existing in vivo in the membrane and, to some extent, also the light harvesting complex-protein interaction. Secondary hydrophilic interactions are found between a few of the charged residues of the H subunit and the hydrophilic surface of the detergent ring from a neighboring RC molecule. A comparison with a previous study on Rhodopseudomonas viridis crystals [which grow in the presence of lauryldimethylamine N-oxide (LDAO) and belong to a different space group] [Roth, M., Lewit-Bentley, A., Michel, H., Deisenhofer, J., Huber, R., & Oesterhelt, D. (1989) Nature 340, 659-661] shows a quasi identity of shape and position of the beta-OG and LDAO rings around the transmembrane alpha helices. The secondary interactions, involving in both cases the external surface of the H subunit, differ because of the different molecular packing in the two space groups. The role and structural requirements of the detergent in the crystallization process are discussed. PMID- 1892842 TI - Recombinant human fibrinogen and sulfation of the gamma' chain. AB - Human fibrinogen and the homodimeric gamma'-chain-containing variant have been expressed in BHK cells using cDNAs coding for the alpha, beta, and gamma (or gamma') chains. The fibrinogens were secreted at levels greater than 4 micrograms (mg of total cell protein)-1 day-1 and were biologically active in clotting assays. Recombinant fibrinogen containing the gamma' chain incorporated 35SO4 into its chains during biosynthesis, while no incorporation occurred in the protein containing the gamma chain. The identity of the sulfated gamma' chain was verified by its ability to form dimers during clotting. In addition, carboxypeptidase Y digestion of the recombinant fibrinogen containing the gamma' chain released 96% of the 35S label from the sulfated chain, and the radioactive material was identified as tyrosine O-sulfate. These results clarify previous findings of the sulfation of tyrosine in human fibrinogen. PMID- 1892843 TI - NMR studies of an oligoproline-containing peptide analogue that binds specifically to the H-2Kd histocompatibility molecule. AB - T lymphocytes expressing variable cell surface antigen receptors recognize "processed" forms of antigen, presented on the surface of other cells by molecules of the major histocompatibility complex (MHC). Naturally processed antigenic peptides can be replaced by synthetic ones. The synthetic peptide AYPPPPPTLA (P5) is an active competitor to the antigenic peptide HLA A24 170-182 (sequence RYLENGKETLQRA) that is recognized by A24 specific T cells in association with the H-2Kd class I MHC molecule. In P5 the five prolines were designed to play the role of a rigid spacer between the residue Y and the T-L unit, so as to mimic the role of Y171, T178, and L179 in the HLA A24 antigenic peptide, since these residues have proven to be the most important with respect to the binding of the HLA A24 peptide with the H-2Kd MHC molecule. Nuclear magnetic resonance studies allow us to demonstrate that in aqueous solution P5 adopts at least three long-lived conformations that can be classified with respect to the Y2-P3-P4 amide bonds as trans-trans, cis-trans, and cis-cis. Among these, the trans-trans form is present in 67% of the molecules while the two others share the remaining 33%. PMID- 1892844 TI - Amino acid sequence of the blue copper protein rusticyanin from Thiobacillus ferrooxidans. AB - Rusticyanin is a small blue copper protein isolated from Thiobacillus ferrooxidans. The amino acid sequence of the rusticyanin has been determined by the structural characterization of tryptic and endoproteinase Asp-N peptides with use of amino terminal microsequencing, fast atom bombardment mass spectrometry, and electrospray triple-quadrupole mass spectrometry techniques. Amino acid analysis, carboxy-terminal sequence analysis, and circular dichroism spectroscopy were also performed on the protein. Amino acid sequence identity among rusticyanin and six other small blue copper proteins is apparent only in the limited C-terminal region of each protein bearing three of the four putative copper ligands. A structural model of the rusticyanin is proposed where the protein is principally a beta-barrel comprised of six strands. This model is consistent with the circular dichroism data and computational predictions of the secondary structure of rusticyanin. A feature of the model is the hypothesis that Asp 73 may serve as a fourth copper ligand. PMID- 1892845 TI - Effect of divers anions on the electron-transfer reaction between iron and rusticyanin from Thiobacillus ferrooxidans. AB - Rusticyanin is a soluble blue copper protein found in abundance in the periplasmic space of Thiobacillus ferrooxidans, an acidophilic bacterium capable of growing chemolithotrophically on soluble ferrous sulfate. The one-electron transfer reactions between soluble iron and purified rusticyanin were studied by stopped-flow spectrophotometry in acidic solutions containing each of 14 different anions. The second-order rate constants for both the Fe(II)-dependent reduction and the Fe(III)-dependent oxidation of the rusticyanin varied as a function of the identity of the principal anion in solution. Analogous electron transfer reactions between soluble iron and bis(dipicolinato)cobaltate(III) or bis(dipicolinato)ferrate(II) were studied by stopped-flow spectrophotometry under solution conditions identical with those of the rusticyanin experiments. Similar anion-dependent reactivity patterns were obtained with soluble iron whether the other reaction partner was rusticyanin or either of the two organometallic complexes. The Marcus theory of outer-sphere electron transfer reactions was applied to this set of kinetic data to demonstrate that the rusticyanin may possess at least two electron-transfer pathways for liganded iron, one where the pattern of electron-transfer reactivity is controlled largely by protein independent activation parameters and one where the protein exhibits an anion dependent kinetic specificity. The exact role of rusticyanin in the iron dependent respiratory electron transport chain of T. ferrooxidans remains unclear. PMID- 1892846 TI - Reexamination of the role of Asp20 in catalysis by bacteriophage T4 lysozyme. AB - Replacement of Asp20 in T4 lysozyme by Cys produces a variant with (1) nearly wild-type specific activity, (2) a newly acquired sensitivity to thiol-modifying reagents, and (3) a pH-activity profile that is very similar to that of the wild type enzyme. These results indicate that the residue at position 20 has a significant nucleophilic function rather than merely an electrostatic role. The intermediate in catalysis by lysozyme is probably a covalent glycosyl-enzyme instead of the ion pair originally proposed. PMID- 1892847 TI - Actinomycin D and 7-aminoactinomycin D binding to single-stranded DNA. AB - The potent RNA polymerase inhibitors actinomycin D and 7-aminoactinomycin D are shown to bind to single-stranded DNAs. The binding occurs with particular DNA sequences containing guanine residues and is characterized by hypochromic UV absorption changes similar to those observed in interactions of the drugs with double-stranded duplex DNAs. The most striking feature of the binding is the dramatic (ca. 37-fold) enhancement in fluorescence that occurs when the 7 aminoactinomycin is bound to certain single-stranded DNAs. This fluorescence of the complex is also characterized by a 40-nm hypsochromic shift in the emission spectrum of the drug and an increase in the emission anisotropy relative to the free drug or the drug bound to calf thymus DNA. The fluorescence lifetimes change in the presence of the single-stranded DNA in a manner compatible with the intensity difference. Thus, there is an increase in the fraction of the emission corresponding to a 2-ns lifetime component compared to the predominant approximately 0.5-ns lifetime of the free drug. The 7-aminoactinomycin D comigrates in polyacrylamide gels with the single-stranded DNAs, and the fluorescence of the bound drug can be visualized by excitation with 540-nm light. The binding interactions are characterized by association constants of 2.0 x 10(6) to 1.1 x 10(7) M-1. PMID- 1892848 TI - Interactions between pressure and ethanol on the formation of interdigitated DPPC liposomes: a study with Prodan fluorescence. AB - Steady-state fluorescence of 6-propionyl-2-(dimethylamino)naphthalene (Prodan) has been employed to study the interacting effects between ethanol and pressure on the formation of the fully interdigitated dipalmitoylphosphatidylcholine (DPPC). At 1 atm and 20 degrees C, a dramatic change in the emission spectrum of Prodan fluorescence is observed at about 1.1-1.3 M ethanol. The emission maximum shifts to longer wavelengths, and the intensity ratio of Prodan fluorescence at 435 nm to that at 510 nm, F435/F510, decreases abruptly with increasing ethanol content. The spectral changes are correlated to the ethanol-induced phase transition of DPPC from the noninterdigitated gel state to the fully interdigitated gel state [Rowe, E.S. (1983) Biochemistry 22, 3299-3305; Simon, S.A., & McIntosh, T.J. (1984) Biochim. Biophys. Acta 773, 169-172]. The spectral changes are attributed to the probe relocation from a less polar environment to a more polar environment due to lipid interdigitation. This relocation is either due to the bulky terminal methyl group of the lipids or due to the partition of Prodan into the bulk solution or both. The present study demonstrates that Prodan is a useful probe in monitoring the formation of the ethanol-induced fully interdigitated DPPC gel phase. Pressure is found to produce spectral changes similar to those induced by ethanol when the ethanol content amounts to 0.8-1.1 M. At lower (e.g., less than 0.4 M) and higher ethanol (e.g., greater than 2.4 M) concentrations, pressure is unable to induce such spectral changes. The critical ethanol concentrations for the formation of the fully interdigitated DPPC gel phase (Cr) have been determined.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1892849 TI - Structural basis for the inactivation of the P54 mutant of beta-lactamase from Staphylococcus aureus PC1. AB - The crystal structure of a mutant protein of a class A beta-lactamase from Staphylococcus aureus PC1, in which Asp179 is replaced by an asparagine (P54), has been determined and refined at 2.3-A resolution (1 A = 0.1 nm). The resulting crystallographic R factor [formula: see text] are the observed and calculated structure factor amplitudes) is 0.181 for 12289 reflections with I greater than or equal to sigma (I) within the 6.0-2.3-A resolution range. The mutated residue is located at the C-terminus of an extensive loop (the omega-loop), remote from the active site, and results in a drastically reduced activity. Examination of the native and P54 structures reveals that the overall fold is similar, except that there is substantial disorder of the omega-loop of P54. This is a consequence of the elimination of a salt bridge between Asp179 and Arg164 that links the two ends of the omega-loop in native beta-lactamase. It is associated with a difference in side-chain conformation between Asn179 in P54 and Asp179 in the native structure. An alternate interaction occurs in P54 between Asn179 and Ala69, adjacent to the catalytic Ser70. This disorder affects catalysis since some of the disordered residues, in particular Glu166, form part of the active site.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1892850 TI - Nuclear matrix localization and specific matrix DNA binding by receptor binding factor 1 of the avian oviduct progesterone receptor. AB - A chromatin acceptor protein for the avian oviduct progesterone receptor (PR), termed receptor binding factor 1 (RBF-1), has recently been shown to (1) be a component of the nuclear binding sites (acceptor sites) for PR and (2) generate high-affinity binding sites (termed the RBF-1 class of sites) on avian genomic DNA [Schuchard et al. (1991) Biochemistry 30, 4535-4542]. A second class of sites and its associated protein (termed RBF-2) were also identified. This paper demonstrates that RBF-1 and also the PR nuclear binding sites are localized in the oviduct nuclear matrix. RBF-1 is found in abundance in the nuclear matrix of liver but only in traces in the nuclear matrix of spleen. Extraction of the nuclear matrix with 4.0 M Gdn-HCl results in the complete removal of RBF-1 as occurs with whole chromatin. Interestingly, a second class of specific PR binding, termed RBF-2, remains on the nuclear matrix after the removal of all RBF 1. Southern blot analysis indicates that the nuclear matrix DNA contains sequences homologous with the 5'-flanking domains of the rapidly steroid regulated c-myc and c-jun protooncogenes and the beta-actin gene, but not genomic sequences of the late sex steroid regulated gene, ovalbumin, or the alpha-actin gene. A specific, small region in the 5'-flanking domain of the c-myc gene appears to be associated with the nuclear matrix. Southwestern blot analysis using partially purified RBF-1 shows a marked affinity and specificity of the RBF 1 for the nuclear matrix DNA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1892851 TI - Enrichment of a second class of native acceptor sites for the avian oviduct progesterone receptor as intact chromatin fragments. AB - Several classes of specific progesterone receptor (PR) nuclear binding sites (acceptor sites) have previously been identified in avian oviduct chromatin on the basis of different binding affinities. Recently, two classes of acceptor proteins (AP) that are associated with these binding sites in the avian oviduct have been identified. These APs were termed receptor binding factors (RBF-1 and 2), and one (RBF-1) has been purified [Schuchard et al. (1991) Biochemistry 30, 4535-4542]. The RBF-1 is associated with the highest affinity class of sites in the intact chromatin, and the RBF-2 is associated with the second highest affinity class of sites. The PR binding sites and their associated RBF-2 protein remain with the residual chromatin fraction following extraction by 4 M Gdn-HCl. This Gdn-HCl-treated chromatin has been termed nucleoacidic protein (NAP). This paper describes the 200-fold enrichment of the native RBF-2 class of PR acceptor sites beginning with the DNase I digestion of NAP to obtain DNase-resistant fragment (NAPf) containing approximately 150 bp of DNA. The PR binding sites are further enriched by high-performance or fast protein liquid chromatography and chromatofocusing. Anti-RBF-1/RBF-2 protein antibodies identify antigens that coelute with the PR binding activity. Hybridization analysis of the DNAf from the enriched NAPf demonstrates sequence homologies with the nuclear matrix DNA as well as with genomic sequences of the rapid steroid responding nuclear protooncogenes c-myc and c-jun. However, comparative analyses of the whole genomic DNA with the nuclear matrix DNA indicate that the RBF-2 (NAPf) is largely nonnuclear matrix.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1892853 TI - Spermine uptake by rat intestinal brush-border membrane vesicles. AB - The uptake of spermine by isolated rat intestinal brush-border membrane vesicles was studied. Uptake was biphasic, with an initial rapid uptake followed by a prolonged slower phase. Spermine uptake was not affected by a Na+ electrochemical gradient. The equilibrium uptake of spermine was considerably dependent upon the medium pH. At pH 7.5 the degree of uptake was higher than that at pH 6.5 and was inversely proportional to the extravesicular osmolarity with a relatively high binding, which was estimated by extraporation to infinite extravesicular osmolarity (zero intravesicular space), while the uptake at pH 6.5 was not altered under the various medium osmolarities. A kinetic analysis of the initial uptake rate of spermine at 37 degrees C gave a Km of 24.2 microM and Vmax of 206.1 pmol/mg protein per min. Furthermore, the uptake at 4 degrees C was nonlinear, providing evidence for saturability. These findings suggest that spermine was associated with intestinal brush-border membrane vesicles in two ways, by binding to the outside and inside of membrane vesicles. The interaction of spermine and the apical membrane can be a contributory factor in the accumulation of this polyamine in the intestine of the intact animal. PMID- 1892852 TI - C-reactive protein (CRP) of the Syrian hamster. AB - Complementary and genomic clones encoding the mRNA and gene for a protein in the Syrian hamster that is highly homologous to C-reactive protein (CRP) have been isolated and studied. Coding sequence of the genomic clone is identical with that of the cDNA clone and predicts a mature protein of 206 amino acids and a 19 amino acid signal peptide. The single intron is 217 base pairs long and contains a short repetitive (GT)n motif. RNA blot analysis demonstrates that mRNA for hamster CRP is approximately 2.0 kb long, and unlike the closely related pentraxin female protein (FP), expression of this mRNA is not affected by the gender of the animal and accumulates equally in males and females during inflammation. In vivo administration of interleukin 1, interleukin 6, and tumor necrosis factor induces accumulation of hepatic CRP mRNA, and the acute-phase alterations in CRP mRNA levels arise as a result of enhanced gene transcription. PMID- 1892854 TI - Interaction of amphiphilic substrates (acyl-CoAs) and their metabolites (free fatty acids) with microsomes from mouse sciatic nerves. AB - We have measured the partition of stearoyl-CoA and oleoyl-CoA between an aqueous phase and the microsomes from mouse sciatic nerves. A method of microultracentrifugation was used which allowed us to study separately the aqueous phase and the biological membranes. We observed that the partition is dependent upon the amount of acyl-CoAs and membrane proteins but seems to be independent of time. A theoretical analysis of these data allowed interpretation of the binding and release in terms of acyl-CoA surface density in the vesicles. We have also analyzed the fate of the membrane-bound acyl-CoAs. We show that, whereas the apparent partition does not seem to vary, the hydrolysis of the membrane-bound acyl-CoAs followed by the release of free fatty acids from the membrane leads to a modification of the partition of acyl-CoAs between the membrane and the aqueous phase. We propose that there is a constant partition of the aliphatic chains (acyl-CoAs + free fatty acids). PMID- 1892855 TI - Transport of phosphatidylinositol to rat hepatocyte plasma membrane catalyzed by phosphatidylinositol transfer protein. AB - Plasma membrane sheets were isolated from fresh rat liver and characterized by electron microscopy and marker enzyme activities. Plasma membrane sheets were used as the acceptor membrane in the measure of transport of phosphatidyl[3H]inositol from small unilamellar phospholipid vesicles or rough endoplasmic reticulum donor membranes. Catalysis of this transport was achieved with phosphatidylinositol transfer protein purified from rat or bovine brain. Assays were designed to separate donor and acceptor membranes by density gradient centrifugation. Rates of transfer were directly proportional to incubation time and the amounts of transfer protein and plasma membrane sheet added. These results are discussed in terms of cellular phosphatidylinositol metabolism, membrane phospholipid composition, and vesicle trafficking in rat hepatocytes. PMID- 1892857 TI - Fluctuation and rotation of human growth hormone-releasing factor in the presence and the absence of phospholipid bilayer analyzed by time-resolved fluorescence depolarization. AB - Time-resolved fluorescence depolarization measurements were carried out for human growth hormone-releasing factor analog ([Trp10]-hGRF (1-29) NH2), where the Trp10 residue was incorporated as a fluorescent probe, in the presence and the absence of 1,2-dimyristoyl-sn-glycero-3-phospho-rac- glycerol(DMPG) liposome and in aqueous 2,2,2-trifluoroethanol (TFE) solution. The fluorescence lifetimes and the rotatory correlation times of the peptide in each medium were determined. The apparent volumes of the rotatory Brownian motion unit calculated from these fluorescent parameters indicate the different mode of the fluctuation and/or the rotation of the peptide in each medium, such as: (i) In the aqueous solution, several segments of the peptide fluctuate individually. (ii) In the DMPG bilayer, both the local fluctuation of Trp residue alone and the rotation of the whole molecule exist. (iii) In the aqueous TFE solution, the monomeric peptide rotates as a rigid ellipsoid. PMID- 1892856 TI - Membrane interaction of 'peptide P' derived from the repeating motif of properdin. AB - A 24 amino acid residue peptide corresponding to the central part of the 'thrombospondin-repeat' motif of the human serum protein properdin was synthesized. The peptide, termed 'peptide P', contains three tryptophans near the N-terminus and an arginine cluster close to the C-terminus. Its sequence closely matches a consensus sequence which has been claimed to characterize a sulfatide binding motif. Membrane binding of peptide P was analyzed using changes in its tryptophan emission upon adding small unilamellar vesicles. The peptide bound to the membranes in a way suggesting simple water/membrane partitioning. Analysis of electrostatic effects at different ionic strengths indicated small electrostatic contributions upon interaction with zwitterionic lipid, despite the large charge number (z = +4) of the peptide. Membrane affinity was increased by one order of magnitude if the bilayers contained 20% of negatively charged lipid. No difference could be detected whether the charged lipid was sulfatide or phosphatidylglycerol. Strong and rapid vesicle aggregation was evident as the peptide associated with the negatively charged vesicles. In addition, a fluorescent energy transfer assay with vesicles and internal total reflection fluorescence microscopy on supported bilayers were used to study membrane interaction of whole human properdin. No sulfatide specificity could be detected. PMID- 1892858 TI - Regulatory changes in the K+, Cl- and water contents of HeLa cells incubated in an isosmotic high K(+)-medium. AB - HeLa cells had their normal medium replaced by an isosmotic medium containing 80 mM K+, 70 mM Na+ and 100 microM ouabain. The cellular contents of K+ first increased and then decreased to the original values, that is, the cells showed a regulatory decrease (RVD) in size. The initial increase was not inhibited by various agents except by substitution of medium Cl- with gluconate. In contrast, the regulatory decrease was inhibited strongly by addition of either 1 mM quinine, 10 microM BAPTA-AM without medium Ca2+, or 0.5 mM DIDS, and partly by either 1 mM EGTA without medium Ca2+, 10 microM trifluoperazine, or substitution of medium Cl- with NO3-. Addition of DIDS to the NO3(-)-substituted medium further suppressed the K+ loss but the effect was incomplete. Intracellular Ca2+ showed a transient increase after the medium replacement. These results suggest that the initial increase in cell K+ is a phenomenon related to osmotic water movement toward Donnan equilibrium, whereas the regulatory K+ decrease is caused by K+ efflux through Ca(2+)-dependent K+ channels. The K+ decrease induced a decrease in cellular water, i.e., RVD. The K+ efflux may be more selectively associated with Cl- efflux through DIDS-sensitive channels than the efflux of other anions. PMID- 1892859 TI - Effect of the antitumour protein alpha-sarcin on the thermotropic behaviour of acid phospholipid vesicles. AB - The antitumour protein alpha-sarcin modifies the thermotropic behaviour of phospholipid vesicles. This has been studied by fluorescence depolarization measurements and differential scanning calorimetry. A surface protein phospholipid interaction is detected by measuring the polarization degree of TMA DPH-labelled vesicles. At the higher protein/lipid molar ratios studied, the alpha-sarcin-vesicles complexes exhibit different thermotropic behaviour depending on whether they are prepared above or below the Tm of the corresponding phospholipid. Labelling of the protein with photoactive phospholipids has also been considered. alpha-Sarcin penetrates the bilayer deep enough to be labelled with the photoactive group located at the C-12 of the fatty acid acyl chain of phospholipids forming vesicles. PMID- 1892860 TI - Sodium-calcium exchange in membrane vesicles from aortic myocytes: stimulation by endogenous proteolysis masks inactivation during vesicle preparation. AB - Plasma membrane vesicles were purified from rat aortic myocytes by centrifugation in a discontinuous sucrose gradient. Vesicles were prepared in the presence or absence of five proteinase inhibitors (aprotinin, benzamidine, leupeptin, pepstatin A and phenylmethylsulfonyl fluoride). The proteinase inhibitors decreased the Vmax by 3.4-fold and had no effect on the Km for Ca2+ of Na+ gradient-dependent 45Ca2+ influx. The proteinase inhibitors had no direct effect on exchange activity, and they had no effect on membrane purity as indicated by 5'-nucleotidase activity. Removing the proteinase inhibitors or adding trypsin or chymotrypsin increased exchange activity approx. 2-fold. The Vmax of exchange activity in intact aortic myocytes is approx. 10-fold higher than the Vmax in plasma membrane vesicles prepared in the presence of proteinase inhibitors. Exchange activity in plasma membrane vesicles is only a sixtieth of the expected value, because the vesicles have approx. 7-fold higher 5'-nucleotidase activity and approx. 6-fold higher specific exchange activity than the crude homogenate. The large loss of exchange activity may be caused by a change in a regulatory domain of the exchanger because endogenous proteolysis restores some of the activity lost during vesicle preparation. PMID- 1892861 TI - Preparation and characterization of polymer coated small unilamellar vesicles. AB - Glucose oxidase was entrapped in small unilamellar vesicles composed of phosphatidylcholine, dicetyl phosphate and cholesterol. Prediction of the enzyme content of liposomes by calculations based on input concentrations of lipid and protein, dimensions of the lipids and the liposomes yielded one protein per vesicle. The entrapment efficiency was experimentally determined to be about 13%. On the other hand the entrapment efficiency for the small chromate ions was found to be significantly lower (0.1%). The liposomes were then coated with a polymer, poly(1,4-pyridinium diylethylene salt). It was possible to remove the lipoid material from underneath the polymer layer with various techniques. The effect of sonication and treatment with organic solvents (tested for this purpose) on enzyme activity were found to be very significant and Triton X-100 was chosen for this purpose. It was shown that the enzyme within the remaining net has 89% of its original activity. PMID- 1892862 TI - A method for preparing analytically pure sodium dithionite. Dithionite quality and observed nitrogenase-specific activities. AB - Sodium dithionite (Na2S2O4) is widely used as a reductant in biochemical studies, but has not been available in its pure form. A convenient, detailed procedure is given for the recrystallization of commercial dithionite from 0.1 M NaOH-methanol under anaerobic conditions. Twice-recrystallized dithionite had a purity of 99 +/ 1% by UV spectroscopy (A315) and elemental analysis. The influence of dithionite quality on the apparent reduction activities of the nitrogenase components (Av1 and Av2) from Azotobacter vinelandii was investigated. PMID- 1892863 TI - Fructose-induced fluorescence generation of reductively methylated glycated bovine serum albumin: evidence for nonenzymatic glycation of Amadori adducts. AB - In vitro glycation of bovine serum albumin by fructose (fructation) induces fluorescence generation about 10-times faster than glucose (G. Suarez et al. (1989) J. Biol. Chem. 264, 3674-3679). In order to gain further insight into possible mechanisms that would explain this difference, the protein was glycated with either glucose or fructose and then reincubated in the absence of sugars. In contrast to the previous findings, albumin that had been glycated with glucose generated fluorescence at a higher rate during the sugar-free incubation. However, when partially glycated BSA was reincubated with sugars under conditions where de novo glycation was prevented by reductive methylation of amino groups fructose induced fluorescence to a much larger extent than glucose. These results are consistent with the notion of covalent addition of sugars to Amadori groups, the earliest stable products of the Maillard reaction. A chemical pathway is proposed where pyrrolic structures result from the double sugar adducts by aldol condensation and dehydration. These structures might be precursors of fluorophores. PMID- 1892864 TI - Vitamin B12 metabolism in a photosynthesizing green alga, Chlamydomonas reinhardtii. AB - To elucidate vitamin B12 (cobalamin) metabolism in green algae, Chlamydomonas reinhardtii was labeled with radioactive cobalamin for 4 days. The Chlamydomonas cells did not require cobalamin for growth, but nevertheless took up and accumulated exogenous cobalamin. The level of the accumulated cobalamin reached a maximum (about 20 fmol/10(6) cells) at day 1 of the cell growth. The cobalamin accumulated by the 4-day cells was partly converted to the coenzymes (5' deoxyadenosylcobalamin, 20.7% and methylcobalamin, 4.8%). The cells contained NADH- and NADPH-linked aquacobalamin reductases (35.9 and 31.5 nmol/min per mg protein, respectively) involved in the synthesis of the coenzymes. Most of the accumulated cobalamin was associated with two heat-labile macromolecules; the coenzymes synthesized were recovered in the macromolecular fraction with a molecular weight of 230,000, while non-coenzyme forms (cyanocobalamin and hydroxocobalamin) predominated in that with a molecular weight of 40,000. Evidence for de novo biosynthesis of cobalamin was also obtained in the alga, indicating that it has both ability to synthesize cobalamin and take up the exogenous vitamin. PMID- 1892865 TI - A wavelength dependent mechanism for rose bengal-sensitized photoinhibition of red cell acetylcholinesterase. AB - A 2-fold enhancement in the efficiency of rose bengal-photosensitized inhibition of red cell acetylcholinesterase activity was observed upon excitation of the dye in the ultraviolet (UV) (313 nm) compared to irradiation in the visible (514 or 550 nm). The measurements of efficiency of photosensitized enzyme inhibition were based on the effect produced when the same number of photons are absorbed by rose bengal (RB) at each wavelength. The mechanism for this unexpected enhancement of RB photosensitization upon UV excitation was investigated. The yield of singlet oxygen (O2(1 delta g], detected by time-resolved luminescence at 1270 nm, was independent of excitation wavelength for RB. Radicals were produced upon irradiation of RB at 313 nm but not at 514 nm as detected by bleaching of N,N dimethylnitrosoaniline (RNO). Irradiation of RB at 313 nm but not at 514 nm appeared to cause homolytic cleavage of carbon-iodine bonds in the dye because iodine radicals, I, detected as I2 were produced with a quantum yield of 0.0041 +/- 0.0005 upon excitation in the UV. Photolysis of I2 in the presence of RNO caused bleaching of the RNO absorption at 440 nm, apparently resulting from reaction of I with RNO. Thus, the enhanced photosensitization upon UV excitation of RB is attributed to formation of I and/or RB. These results indicate that radicals, produced with low relative yield but having high reactivity compared to O2(1 delta g), can contribute to photosensitized enzyme inhibition and may represent an alternative mechanism for photodynamic therapy. PMID- 1892866 TI - Synthesis of a radioactive labeled undecagoldcluster for application in X-ray structure analysis of ribosomes. AB - In order to quantitate and to determine the extent of binding of a heavy atom derivative to ribosomal particles and other components of protein biosynthesis, we prepared a 14C-radioactive labeled monofunctional undecagoldcluster. This cluster can be bound either to exposed sulfhydryl groups at the surface of the ribosomes and its subunits, or to high nucleophilic amino groups of nucleic acids as well as to proteins. PMID- 1892867 TI - Aldehyde dismutation catalyzed by pulmonary carbonyl reductase: kinetic studies of chloral hydrate metabolism to trichloroacetic acid and trichloroethanol. AB - The kinetics of the NAD(P)(+)-linked aldehyde dismutation by pulmonary carbonyl reductase of guinea pig were studied using a highly hydrated substrate, chloral hydrate (CH). The enzyme irreversibly converted the substrate into trichloroacetic acid (TCA) and trichloroethanol (TCE) in the presence of the reduced or oxidized cofactors, of which NAD(P)+ gave a higher reaction rate than did NAD(P)H, and the concentration ratios of the two products (TCA plus TCE) to CH utilized were 1:1. In the NAD(P)(+)-linked reaction TCA was the predominant product and its amount was compatible with that of TCE plus NAD(P)H produced, whereas in the NAD(P)H-linked reaction equal amounts of TCA and TCE were formed and the cofactor was little oxidized. These results suggest that the enzyme oxidized the hydrated aldehydes to TCA with NAD(P)+ as the cofactor and reduced the unhydrated aldehyde to TCE with NAD(P)H. The steady-state kinetic measurements in the NADP(+)-linked CH oxidation were consistent with an ordered Bi Bi mechanism which is the same as that for the secondary alcohol oxidation by the enzyme. The dehydrogenase activity was inhibited competitively with respect to CH by a secondary alcohol substrate, propan-2-ol. The CH and propan-2-ol dehydrogenase activities were similarly inactivated by 2,4,6-trinitrobenzene sulfonate, and NADP(H), several cofactor analogs and a cofactor-competitive inhibitor, Cibacron blue dye, protected against the inactivation, which suggest that lysine residues are essential for catalysis. PMID- 1892868 TI - Sensitive immunoassay for rat parvalbumin: tissue distribution and developmental changes. AB - A sensitive enzyme immunoassay for measurements of rat parvalbumin was established using antibodies raised in rabbits with parvalbumin purified from skeletal muscles. Antibodies in the antiserum were purified with a parvalbumin coupled Sepharose column. The sandwich-type immunoassay system for parvalbumin was composed of polystyrene balls with immobilized purified antibodies and the same antibodies labeled with beta-D-galactosidase from Escherichia coli. The assay was highly sensitive and the minimum detection limit was 1 pg parvalbumin/tube. The assay did not cross-react with other calcium binding proteins, including human S-100a0 and S-100b proteins, rat 28-kDa calbindin-D, and bovine calmodulin. High concentrations of parvalbumin were observed in the skeletal muscles, especially in those composed of fast-twitch fibers, and in the diaphragm and tongue, but not in heart muscle. A relatively high concentration was estimated in the central nervous tissue. Parvalbumin was detected in the cerebral cortex and cerebellum of gestational 15-day fetuses. However, the levels of parvalbumin in the muscle tissues and central nervous tissue were very low in rats before 1 week of age. Thereafter, they increased sharply, reaching the adult levels by 5 weeks in most of the tissues. Parvalbumin concentrations in adult rat soleus muscle increased less than 20-fold within 10 days after transection of the ipsilateral sciatic nerve, while the concentrations in the extensor digitorum longus muscle did not change in the same period. PMID- 1892869 TI - Purification of prokallikrein from bovine pancreas. AB - A prokallikrein was isolated from bovine pancreas by a multi-step procedure involving gel filtration, hydrophobic interaction and anion-exchange chromatographies. The purification was initially monitored by measurement of the kinin-releasing activity of the activated zymogen. Later, when the pure prokallikrein had been isolated, a specific radioimmunoassay for the zymogen was set up and that was employed to provide estimates of 323-fold and 28% for the overall degree of purification and percentage recovery of prokallikrein. The relative molecular weight of prokallikrein was found to be 26,900 by SDS gel electrophoresis and its isoelectric point was established as pH 4.55. PMID- 1892870 TI - Purification and some properties of the squalene-tetrahymanol cyclase from Tetrahymena thermophila. AB - The membrane-bound enzyme from Tetrahymena thermophila responsible for the conversion of squalene into the quasi-hopanoid tetrahymanol was purified 297-fold to near homogeneity. Purification involved solubilization by octylthioglucoside, chromatography on DEAE-trisacryl, hydroxyapatite and FPLC ion-exchange on Mono Q. The apparent KM was found to be 18 microM. 2,3-Iminosqualene and N,N dimethyldodecylamine-N-oxide are effective inhibitors of the cyclase with I50 values of 50 and 30 nM, respectively. The cyclase has a molecular mass of 72 kDa as judged by electrophoresis in polyacrylamide gels under denaturating conditions. The optimal enzymatic activity was obtained at pH 7.0 and 30 degrees C. The solubilized enzyme needs the presence of detergent for maintaining activity. The influence of different detergents on cyclase activity was studied. Triton X-100 proved to be a strong inactivator of the enzyme. Solubilization of the cyclase in Tween 80 and digitonin inactivates the enzyme. However, its activity can be recovered by complementation of the assay buffer with octylthioglucoside above its critical micellar concentration. We suggest that this approach might be applicable to other membrane-bound proteins. PMID- 1892871 TI - Diurnal variations of rat liver enzymes catalyzing cholesterol ester hydrolysis. AB - Cholesterol ester hydrolase activity was determined at 3 h time intervals over 24 h in lysosomes, cytosol and microsomes from ad libitum-fed and 24 h food-deprived female rat liver. Diurnal rhythms were identified for the acid and neutral esterases, which were strikingly changed by fasting. In fed animals, lysosomal esterase specific activity exhibited a peak at noon and a sustained medium rate at early darkness, whereas total esterase was maximal at midnight. The circadian patterns of the cytosolic and the microsomal esterases paralleled each other, though the amplitude of rhythms differed, showing higher activities around midnight. After fasting, cholesterol esterase activity from all cell fractions reached a maximum near dark onset. These results are the first to indicate that cholesteryl ester hydrolysis may play a role in generating the diurnal rhythm of hepatic cholesterol. PMID- 1892872 TI - Decreased serum lipids, serum insulin and triacylglycerol synthesis in adipose tissue of JCR:LA-corpulent rats treated with benfluorex. AB - Rats of the JCR:LA-corpulent strain were treated with benfluorex daily at a dose of 25 mg/kg body weight. This strain of rat, if homozygous for the cp gene (cp/cp), is hyperphagous, obese, hypertriglyceridemic, insulin resistant and in the case of male rats, atherosclerosis prone. The benfluorex treatment produced a sharp reduction in food intake which remained suppressed despite recovery toward normal after 2 weeks of treatment. This was accompanied by sustained decreases in body weight and adipose tissue mass. The ability of adipose tissue from female rats to take up glucose and convert it to lactate, glyceride-glycerol and fatty acids was decreased. This decrease was largely due to decreased adipose tissue mass. The serum concentrations of glucose, lactate, triacylglycerol, cholesterol, phospholipids and insulin were decreased in both sexes. The treatment also improved glucose tolerance and decreased corticosterone concentrations in male rats only. While reduction of food consumption contributes to the effects seen, benfluorex clearly had significant direct metabolic effects. The effects are consistent with an improved insulin sensitivity leading to a decrease in circulating triacylglycerol. The changes produced by benfluorex are all in directions that should inhibit atherogenesis in this animal model for the human obesity/hypertriglyceridemia/insulin resistant syndrome. PMID- 1892873 TI - The effects of probucol on lipoprotein metabolism in the rat. AB - The effects of probucol on liver and intestinal apolipoprotein, LDL-receptor and hepatic lipase gene expression, as well as plasma lipid and apolipoprotein levels and liver lipase activity were evaluated in male rats. Administration of probucol decreased plasma triacylglycerols, without affecting plasma cholesterol. Plasma apo E and apo B concentrations increased after probucol. Since liver and intestinal apo B and apo E mRNA levels remained unchanged, this increase could be attributed to a delayed clearance by the LDL-receptor, whose mRNA levels dropped by 50% in the liver. For the HDL-apolipoproteins, only liver apo A-IV mRNA levels decreased after probucol, which was reflected by a fall of plasma apo A-IV. Neither hepatic lipase activity nor mRNA levels were significantly influenced by probucol. PMID- 1892874 TI - Hydroxyeicosatetraenoic acid oxidation in Chinese hamster ovary cells: a peroxisomal metabolic pathway. AB - To evaluate the peroxisomal requirement for beta-oxidation of hydroxyeicosatetraenoic acids (HETES), we tested 5-, 12- and 15-HETE oxidation in wild-type and mutant Chinese hamster ovary (CHO) cells. Mutant CHO cells contain peroxisomal ghosts, have random cytosolic localization of catalase and lack two of the enzymes necessary for peroxisomal beta-oxidation. Reverse-phase HPLC indicated that 33% of 12-HETE radioactivity was converted by wild-type CHO cells during a 2 h incubation to one major and several minor polar metabolites. Wild type CHO cells also converted 15-HETE to one major and several minor polar metabolites. Neither 12- nor 15-HETE were converted to any metabolites by the mutant CHO cell lines, despite appreciable cellular uptake of these hydroxyeicosanoids. 5-HETE was not converted to any metabolic products by either the wild-type or the mutant CHO cells. Docosahexaenoic acid beta-oxidation was substantially reduced in the mutants as compared to the wild-type cells, palmitic acid beta-oxidation was reduced to an intermediate extent in the mutants, but octanoate beta-oxidation and citrate synthase activity were not impaired. Protein immunoblotting for mitochondrial manganese superoxide dismutase indicated a single band of identity at 20 kDa in both wild-type and mutant CHO cells. Since mutant CHO cells fail to convert 12- and 15-HETE to oxidative metabolites but contain normal mitochondrial enzymatic activities, intact peroxisomes appear to be the organelle responsible for HETE oxidation. PMID- 1892875 TI - Neutral lipid synthesis and accumulation during in vitro induction of the lipocyte phenotype in hepatic connective tissue cells. AB - Connective tissue cells of liver parenchyma are known as hepatic myofibroblasts and lipocytes (fat-storing cells, Ito-cells). They are considered to belong to a single cell lineage, that may switch between these two phenotypes. We have studied cellular and molecular parameters and controls of this switch in the murine GRX cell line, established from liver fibro-granulomatous lesions induced by schistosomal infection. Accumulation of neutral lipids (triacylglycerols, monoalkyl-diacylglycerol, cholesterol) was monitored. It was dependent upon induction with indomethacin. Insulin alone did not induce lipid accumulation in GRX cells, but in cells induced by indomethacin it increased the quantity of stored lipids. We propose that hepatic lipocytes are not cells directly involved in energy storage, but that they represent a particular cell population specialized in storage and in controls of the homoeostasis of lipid-soluble substances at the systemic level. PMID- 1892876 TI - Perinatal development of hepatic cholesterol synthesis in the rat. AB - Rates of cholesterol synthesis and HMG CoA reductase activity in rat liver, have been reported to be high before and low after birth. The timing of the decline in perinatal rates of cholesterol synthesis, however, is uncertain. These studies, therefore, determined in vivo rates of cholesterol synthesis using [3H]water and hepatic reductase activity in vitro in perinatal rats. The lipid composition of the plasma, liver and its microsomal subfraction were also determined. Reductase activity increased during late gestation, remained high immediately after birth, then decreased with the commencement of suckling. Rates of cholesterol synthesis increased from gestation day 18 to 20, but in contrast to reductase activity, decreased on the day before birth. Plasma cholesterol and triacylglycerol levels increased to gestation day 19, then decreased to term. By the 6th h after birth, plasma and liver cholesterol and triacylglycerol levels had increased markedly. By 48 h after birth, the high hepatic cholesterol content was associated with an increase in the cholesteryl ester fraction. The microsomal cholesterol/phospholipid molar ratio decreased from gestation day 16 until 12 h after birth, then increased markedly from 36 to 48 h. There was an apparent inverse relationship between the change in microsomal cholesterol/phospholipid molar ratio and the fatty acid unsaturation index from gestation day 16 to 36 h after birth. The results suggest that in late gestation and before suckling, the low in vivo rate of hepatic cholesterol synthesis may not be due to low activity of HMG CoA reductase. PMID- 1892877 TI - Stereospecificity of the hydroxyeicosatetraenoic and hydroxyoctadecadienoic acids produced by cultured bovine endothelial cells. AB - Characterization of the stereospecificity of the derivatives of arachidonic acid and linoleic acid produced by endothelial cells is needed to define the enzymatic origin of these compounds and their role in vascular physiology. In studies utilizing two bovine endothelial cell lines (CPAE and AG04762), both free 15 hydroxyeicosatetraenoic acid (15-HETE) and 11-hydroxyeicosatetraenoic acid (11 HETE) were generated during incubations with exogenous arachidonic acid and both free 9-hydroxyoctadecadienoic acid (9-HODE) and 13-hydroxyoctadecadienoic acid (13-HODE) were generated during incubations with exogenous linoleic acid. Esterification of 15-HETE, 9-HODE and 13-HODE during these incubations was demonstrated. The analyses included reversed-phase high performance liquid chromatography of the free acid and its methyl ester and chiral separation of the methyl ester on straight phase chiral columns. The ratio of 9-HODE/13-HODE averaged 2.7 in the chromatographic analyses of the extracts of the incubations with linoleic acid. The combined production of 13-HODE and 9-HODE from linoleic acid was four times greater than that of 15-HETE and 11-HETE from arachidonic acid. With regard to the products of the CPAE endothelial cell line, the S/R ratio of the stereoisomers averaged 1.5 for free 15-HETE, 5.7 for free 13-HODE and 0.2 for free 9-HODE. The 11-HETE had strict (R) stereospecificity. The products from the AG04762 endothelial cell line had similar stereochemistry. All these stereochemical findings point to the activity of a cyclooxygenase rather than that of a lipoxygenase. PMID- 1892878 TI - On the conformational, physical properties and functions of polyunsaturated acyl chains. AB - The conformational properties of the acyls of biological membranes--hydrocarbon chains with isolated cis double bonds--were studied by computer simulation. The Monte Carlo method was used, with continuous variation of bond rotation angles within the (0, 360 degree) range considered. It has been shown, that if all double bonds of molecules are separated only by one methylene group, and their number in the chain is maximum, the molecule is characterized by the highest equilibrium flexibility (at temperatures only encountered by biological systems) as compared to any similar molecules. It is such a structure which is inherent to docosahexaenoic acid. The above molecule coefficient that characterizes the temperature sensitivity of the molecule sizes is 10-times lower than that of a saturated chain. The polyunsaturated chain segment with high probability assumes the extended (in perfect crystal structures the 'angle iron-shaped') conformation when all the molecules are efficiently packed below the phase-transition temperatures. The annular lipid layer of embedded enzymes is assumed to be enriched with polyunsaturated fatty acid acyls. The above physical properties of polyunsaturated chains are bound to favour the maintenance of the proper conformational mobility of biomembrane enzymes, to relax the negative influence of environmental temperature changes on their activity. When freezing biological membranes they are bound to provide the molecule packing which is free of high tensions. PMID- 1892879 TI - Sources of diradylglycerols generated during cell growth and phorbol ester stimulation in Madin-Darby canine kidney cells. AB - The molecular species of diacylglycerol and alkylacylglycerol of Madin-Darby canine Kidney (MDCK) cells were analyzed to determine the sources of diradylglycerols generated during cell growth and phorbol ester stimulation. MDCK cells in log phase growth contained higher levels of diacylglycerol and alkylacylglycerol than confluent cells. Both subclasses of diradylglycerol showed higher levels of saturated and monoenoic species during log phase. Glycerol incorporation into diradylglycerols was increased during growth, consistent with an increase in their synthesis de novo. Stimulation with 12-O tetradecanoylphorbol-13-acetate (TPA), a potent activator of protein kinase C, caused an increase in the level of diacylglycerol but not alkylacylglycerol. Log phase MDCK cells showed a greater response to TPA treatment than confluent cells. The molecular species of diacylglycerol generated during stimulation with either TPA or dioctanoylglycerol closely resembled the species of phosphatidylcholine. These results indicate that TPA and synthetic diacylglycerol stimulate endogenous diacylglycerol production through the hydrolysis of phosphatidylcholine. In contrast, the higher content of diacylglycerol and alkylacylglycerol in replicating MDCK cells is the result of an increase in their synthesis de novo. PMID- 1892880 TI - Efflux of phospholipid from fibroblasts with normal and elevated levels of cholesterol. AB - To address the hypothesis that phospholipid efflux from cells contributes to lipoprotein structure, we have examined the efflux of biosynthetically labeled [32P]phospholipid from cells to lipoproteins. With normal human skin fibroblasts in monolayer culture, high density lipoprotein (HDL3) promoted the efflux of phospholipid in a concentration-dependent manner. As analyzed by TLC, the major phospholipids released from fibroblasts were phosphatidylcholine, sphingomyelin, lysophosphatidylcholine and phosphatidylethanolamine. At identical concentrations, HDL3 and dimethylsuberimidate treated-HDL3 promoted similar efflux, suggesting that efflux did not depend on specific binding of HDL3 to the cell surface. When the content of cholesterol in fibroblasts was doubled by pre incubation with LDL and cholesterol-rich liposomes, the fractional efflux of phospholipid to HDL3 and other acceptors was stimulated about 2-fold. Most of this stimulation was due to enhanced release of phosphatidylcholine. Similar effects of enrichment were found with Fu5AH rat hepatoma cells, but not with J774 mouse macrophages. The results support the hypothesis that the efflux of phospholipid from cells contributes to the phospholipid content of HDL. This may enhance the ability of HDL to remove cholesterol from cells, the initial step in reverse cholesterol transport. PMID- 1892881 TI - Calcium regulation of the human PMN cytosolic 15-lipoxygenase. AB - Addition of tracer (pg) amounts of [3H]arachidonic acid to the 120,000 x g cytosolic fraction of human polymorphonuclear leukocytes (PMNs) produced [3H]-15 HETE, the product of the 15-lipoxygenase, as the major metabolite. In the presence of nanomolar and low micromolar amounts of calcium, [3H]-15-HETE formation was increased as much as 15-fold which corresponded to 17% conversion of added substrate. This enhancement of the cytosolic 15-lipoxygenase activity, which was reversible by EGTA, was inhibited by phosphatidyl serine and phosphatidyl choline. Millimolar levels of calcium inhibited the cytosolic 15 lipoxygenase and the 5-lipoxygenase product 5-HETE could reverse this inhibition. These results indicate that calcium is an important modulator of the PMN 15 lipoxygenase when the enzyme is in a cytosolic milieu. PMID- 1892882 TI - Dietary regulation of maternal and fetal cholesterol metabolism in the guinea pig. AB - Studies to determine the effects of pre-natal interventions on maternal and fetal cholesterol homeostasis were carried out in the guinea pig. Guinea pig dams were fed either non-purified guinea pig diet or diet supplemented with either 1.1% of the bile acid binding resin cholestyramine or 0.25% cholesterol. Whole body rates of endogenous cholesterol synthesis were determined by quantitation of [3H]water incorporation into digitonin precipitable sterols in non-pregnant animals and at 40 and 60 days of gestation in the dam and fetus. Maternal hepatic cholesterol synthesis was reduced 87% by dietary cholesterol and was increased 3.5-fold with cholestyramine feeding. Fetal hepatic and peripheral tissue cholesterol synthesis rates peaked at 40 days gestation when peripheral tissue cholesterol synthesis was 5.7-fold higher and hepatic synthesis 6.2-fold greater than the near adult levels observed at 60 days. Cholesterol synthesis in the fetus was relatively insensitive to dietary manipulations; however, maternal cholestyramine treatment did result in a 1.4-fold increase in fetal carcass cholesterol synthesis at 60 days gestation. These data demonstrate that maternal cholesterogenic systems maintain responsiveness to dietary regulation during pregnancy; whereas fetal cholesterol homeostasis is relatively insensitive to dietary cholesterol throughout gestation yet may respond to induction by maternal cholestyramine treatment during the late gestation period. PMID- 1892883 TI - Metabolic aspects of peroxisomal beta-oxidation. AB - In the course of the last decade peroxisomal beta-oxidation has emerged as a metabolic process indispensable to normal physiology. Peroxisomes beta-oxidize fatty acids, dicarboxylic acids, prostaglandins and various fatty acid analogues. Other compounds possessing an alkyl-group of six to eight carbon atoms (many substituted fatty acids) are initially omega-oxidized in endoplasmic reticulum. The resulting carboxyalkyl-groups are subsequently chain-shortened by beta oxidation in peroxisomes. Peroxisomal beta-oxidation is therefore, in contrast to mitochondrial beta-oxidation, characterized by a very broad substrate specificity. Acyl-CoA oxidases initiate the cycle of beta-oxidation of acyl-CoA esters. The next steps involve the bi(tri)functional enzyme, which possesses active sites for enoyl-CoA hydratase-, beta-hydroxyacyl-CoA dehydrogenase- and for delta 2, delta 5 enoyl-CoA isomerase activity. The beta-oxidation sequence is completed by a beta-ketoacyl-CoA thiolase. The peroxisomes also contain a 2,4 dienoyl-CoA reductase, which is required for beta-oxidation of unsaturated fatty acids. The peroxisomal beta-hydroxyacyl-CoA epimerase activity is due to the combined action of two enoyl-CoA hydratases. (For a recent review of the enzymology of beta-oxidation enzymes see Ref. 225.) The broad specificity of peroxisomal beta-oxidation is in part due to the presence of at least two acyl CoA oxidases, one of which, the trihydroxy-5 beta-cholestanoyl-CoA (THCA-CoA) oxidase, is responsible for the initial dehydrogenation of the omega-oxidized cholesterol side-chain, initially hydroxylated in mitochondria. Shortening of this side-chain results in formation of bile acids and of propionyl-CoA. In relation to its mitochondrial counterpart, peroxisomal beta-oxidation in rat liver is characterized by a high extent of induction following exposure of rats to a variety of amphipathic compounds possessing a carboxylic-, or sulphonic acid group. In rats some high fat diets cause induction of peroxisomal fatty acid beta oxidation and of trihydroxy-5 beta-cholestanoyl-CoA oxidase. Induction involves increased rates of synthesis of the appropriate mRNA molecules. Increased half lives of mRNA- and enzyme molecules may also be involved. Recent findings of the involvement of a member of the steroid hormone receptor superfamily during induction, suggest that induction of peroxisomal beta-oxidation represents another regulatory phenomenon controlled by nuclear receptor proteins. This will likely be an area of intense future research. Chain-shortening of fatty acids, rather than their complete beta-oxidation, is the prominent feature of peroxisomal beta-oxidation.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1892884 TI - Effect of vitamin E on arachidonic acid peroxidation and its binding to Chinese hamster V79 cell DNA. AB - Following 24 h incubation in standard culture medium (containing 2 microM of arachidonic acid, AA), and 10 and 20 microM supplemented AA, approx. 55, 40 and 33%, respectively, of the fatty acid was incorporated into Chinese hamster V79 cell lipids. The AA content of cells increased 5 to 7-fold with the 10 and 20 microM supplementations of AA and, there was a correspondingly marked decrease in the proportion of AA incorporated into phospholipids (94 vs. 50 and 32%), whereas an increased percentage of AA was recovered in triacylglycerols (1 vs. 30 and 50%) and free fatty acids (1 vs. 3 and 8%). AA at 12 and 22 microM induced a 50 and 80% increase, respectively, in cellular content of thiobarbituric acid reactive substances (TBARS), an indication of increased peroxidation of cell lipids. This formation of TBARS was inhibited by vitamin E but not by indomethacin or SKF-525. Binding of [3H]AA-derived counts to DNA increased in parallel to the levels of cellular lipid peroxidation. Vitamin E added to the culture medium at 10(-4) M was readily taken up by the cells within 48 h and significantly reduced both lipid peroxidation and binding of AA-derived counts to DNA, without affecting AA uptake. Cell vitamin E content was significantly reduced following 24 h incubation in the presence of 10 and 20 microM supplemented AA. This study indicates that products of lipid peroxidation can bind to DNA in cultured cells, and points to a potential cyto- and geno-toxic risk posed by increased cellular AA content relative to anti-oxidant defenses. PMID- 1892885 TI - Evidence that the rate of phosphatidylcholine catabolism is regulated in cultured rat hepatocytes. AB - The regulation of phosphatidylcholine (PC) catabolism has been studied in choline deficient rat hepatocytes. Supplementation of choline-deficient hepatocytes, prelabeled with [3H]choline, with 100 microM choline increased the rate of PC catabolism by approx. 2-fold. The major product of PC degradation was glycerophosphocholine in both choline-deficient and choline-supplemented cells. Choline supplementation decreased the radioactivity recovered in lysoPC by 50%. This effect was accompanied by a 2-fold increase of labeled glycerophosphocholine. Comparable results were obtained when PC of the cells was prelabeled with [3H]methionine or [3H]glycerol. The activity of phospholipase A in cytosol, mitochondria and microsomes isolated from choline-deficient rat liver was similar to the activity in control liver, when determined with [3H]PC vesicles as the substrate. Measurement of the activity of phospholipase A with endogenously [3H]choline-labeled PC showed that the formation of lysoPC in mitochondria isolated form choline-supplemented cells was 40% lower than in choline-deficient cells. Alternatively, the formation of [3H]glycerophosphocholine and [3H]choline in microsomes from choline-supplemented cells was significantly higher (1.4-fold) than in microsomes from choline deficient cells. These results suggest that the rate of PC catabolism is regulated in rat hepatocytes and that the concentration of PC might be an important regulatory factor. PMID- 1892886 TI - Head group specificity in the regulation of phosphatidylcholine catabolism in rat hepatocytes. AB - Previous studies have shown that the catabolism of PC is regulated in choline deficient hepatocytes and the concentration of phosphatidylcholine (PC) might be an important regulatory factor (Tijburg, L.B.M., Nishimaki-Mogami, T. and Vance, D.E. (1991) Biochim. Biophys. Acta, 1085, 167-177). In the present study we investigated the head group specificity of the regulation of PC catabolism. Supplementation of choline-deficient rat hepatocytes, prelabeled with [3H]choline, with dimethylethanolamine increased the catabolism of PC by 1.6-fold after 6 h. This effect was accompanied by a 2.5-fold increase in the production of [3H]glycerophosphocholine (GPC). Radioactivity associated with lysoPC was decreased by 50% in dimethylethanolamine-treated cells. Supplementation of the cells with monomethylethanolamine had little effect on the degradation of PC. In other experiments choline-deficient cells were prelabeled with [3H]methionine. Treatment of the cells with dimethylethanolamine increased the formation of [3H]GPC by 5-fold, while the production of lysoPC was inhibited by 60%. Supplementation of the medium with monomethylethanolamine resulted in a 2-fold increase in labeled GPC, with a concomitant decrease of [3H]lysoPC by approx. 25%. We conclude that the formation of phosphatidyldimethylethanolamine from its corresponding base mimics the effect of the synthesis of PC from choline in increasing PC catabolism, whereas the effect of monomethylethanolamine is much less pronounced. PMID- 1892887 TI - Evidence that remodeling of the fatty acids of phosphatidylcholine is regulated in isolated rat hepatocytes and involves both the sn-1 and sn-2 positions. AB - The remodeling of the fatty acyl moieties of phosphatidylcholine (PC) has been studied in choline-deficient and choline-supplemented hepatocytes prepared from a choline-deficient rat. Choline-deficient hepatocytes were prelabeled with [Me 3H]choline for 30 min and subsequently incubated for up to 12 h in the presence or absence of choline. Analysis of the molecular species of PC from choline deficient cells showed that, at the end of the pulse, approx. 75% of the label was incorporated into palmitate-containing species and only approx. 16% of the labeled species contained stearate. During the chase period there was a redistribution of label and after 12 h approx. 56% of the total radioactivity was associated with palmitate containing species and 37% was recovered in stearate containing species. A similar distribution of radioactivity was observed in choline-supplemented cells. Measurement of the specific radioactivity of the major molecular species of PC was consistent with a precursor-product relationship between palmitate-containing species and stearate-containing species with arachidonate or linoleate on the sn-2 position. A model is presented which takes into account remodeling of both the sn-1 and sn-2 positions of PC. PMID- 1892888 TI - Arachidonic acid metabolism during antigen and ionophore activation of the mouse bone marrow derived mast cell. AB - This study has examined the metabolism of arachidonic acid in the mouse bone marrow-derived mast cell (BMMC) during immunologic and nonimmunologic activation. The predominant pools of endogenous arachidonate in the mast cells were found in ethanolamine (46%), choline (39%) and inositol (14%) containing glycerolipids. Initial studies established conditions where equilibrium labelling of these major phospholipids in the BMMC could be reached. Upon challenge, arachidonate was lost from all major phospholipid classes (phosphatidylethanolamine greater than phosphatidylcholine greater than phosphatidylinositol). There was a small but significant increase in the amount of label associated with phosphatidic acid during cell activation. Arachidonate was distributed among 1-acyl, 1-alkyl and 1 alk-1-enyl-linked subclasses of PC and PE. The rank order of loss of labelled arachidonate from the major PE and PC subclasses during antigen and ionophore activation was 1-alk-enyl-2-arachidonoyl-GPE greater than 1-acyl-2-arachidonoyl GPC greater than 1-acyl-2-arachidonoyl-GPE greater than 1-alkyl-2-arachidonoyl GPC. Labelled products released into the supernatant fluids and free arachidonic acid within the cell accounted for the bulk of arachidonate lost from phospholipids. Labelled products in the supernatant fluids were composed of LTB4, LTC4, PGD2 and free arachidonic acid. BMMC phospholipids were also labelled for 24 hr with [3H]choline, [3H]myoinositol or [14H]ethanolamine and labelled 2-lyso phospholipids were measured after cell activation. Radioactivity in lysophospholipids from PC, PE and PI increased significantly between 30 s and 2 min after antigen activation and then declined. Taken together, these studies suggest that arachidonate is mobilized predominantly from PE and in particular 1 alk-1-enyl-2-arachidonoyl-GPE by the direct removal of arachidonate from the sn-2 position of the molecule. Most of this arachidonate is then released from cells as eicosanoids or free fatty acid. PMID- 1892889 TI - Characterization of several phospholipase activities and diacylglycerol/2 monoacylglycerol lipases in rat alveolar macrophages. AB - We measured phospholipase activities in both the microsomal and the cytosolic enriched fractions of rat alveolar macrophages by using exogenous arachidonic acid-labeled phospholipids. The microsomal fractions contain a neutral calcium independent phospholipase A2 (PLA2) which acts on substrates phosphatidylcholine (PC) and phosphatidylinositol (PI), a calcium-independent PLA2 acting on phosphatidylethanolamine (PE), and a neutral calcium-dependent PI-specific PLC. The cytosolic fractions contain calcium-dependent phospholipase: PLA2 that hydrolyses PC at alkaline pH, and a neutral PI-specific phospholipase C (PLC). The largest release of arachidonic acid from PI occurred with the cytosolic fractions at pH 6 in the presence of calcium. That hydrolysis involved a PLA2, and a PLC followed by the action of a diacyglycerol and 2-monoacylglycerol lipases. The cytosol also contains a calcium-independent PLA2 acting on PE. Our investigation shows that rat alveolar macrophages possess a number of phospholipases, as well as diacylglycerol and 2-monoacylglycerol lipases. The above enzymes could play an essential role in the remodeling of membrane phospholipids in resting cells, and the generation of physiologically active lipids in activated cells. PMID- 1892890 TI - Effects of various non-esterified fatty acids on the transfer of cholesteryl esters from HDL to LDL induced by the cholesteryl ester transfer protein. AB - The effects of saturated, monounsaturated and polyunsaturated non-esterified fatty acids on the rate of transfer of radiolabeled cholesteryl esters from high density lipoproteins (HDL) to low density lipoproteins (LDL), induced by the cholesteryl ester transfer protein (CETP), have been studied. Human high-density lipoproteins-subfraction 3 (HDL3) containing radiolabeled cholesteryl esters were incubated with LDL at 37 degrees C with or without CETP and in the absence or in the presence of non-esterified fatty acids. Less than 6% of the total radioactivity was recovered in the LDL fraction after incubation of HDL3, and LDL for 3 h at 37 degrees C in the absence of CETP, regardless of whether or not non esterified fatty acids were added. The addition of CETP to the incubation mixture induced a time-dependent redistribution of radiolabeled cholesteryl esters from HDL3 to LDL. Non-esterified fatty acids were found to alter the rate of transfer of cholesteryl esters induced by CETP. While short chain saturated non-esterified fatty acids (caprylic and capric acids) had no effect on the rate of transfer of cholesteryl esters, the medium and long chain ones (lauric, myristic, palmitic and stearic acids) significantly increased the CETP-mediated transfers from HDL3 to LDL. At low concentrations, unsaturated fatty acids also stimulated the CETP mediated redistribution of radiolabeled cholesteryl esters from HDL3 to LDL. As the concentration of either oleic, linoleic or arachidonic acids increased to higher levels, a significant proportion of fatty acids remained unassociated with lipoprotein particles. Under these circumstances the transfer process was inhibited. These results show that non-esterified fatty acids can modulate the CETP-mediated transfer of cholesteryl esters from HDL to LDL and that this effect is dependent on both the length and the degree of unsaturation of their monomeric carbon chain. PMID- 1892891 TI - Isolation and characterization of carnitine acetyltransferase from S. cerevisiae. AB - Carnitine acetyltransferase was isolated from yeast Saccharomyces cerevisiae with an apparent molecular weight of 400,000. The enzyme contains identical subunits of 65,000 Da. The Km values of the isolated enzyme for acetyl-CoA and for carnitine were 17.7 microM and 180 microM, respectively. Carnitine acetyltransferase is an inducible enzyme, a 15-fold increase in the enzyme activity was found when the cells were grown on glycerol instead of glucose. Carnitine acetyltransferase, similarly to citrate synthase, has a double localization (approx. 80% of the enzyme is mitochondrial), while acetyl-CoA synthetase was found only in the cytosol. In the mitochondria carnitine acetyltransferase is located in the matrix space. The incorporation of 14C into CO2 and in lipids showed a similar ratio, 2.9 and 2.6, when the substrate was [1 14C]acetate and [1-14C]acetylcarnitine, respectively. Based on these results carnitine acetyltransferase can be considered as an enzyme necessary for acetate metabolism by transporting the activated acetyl group from the cytosol into the mitochondrial matrix. PMID- 1892892 TI - Physical and biological properties of fluorescent dansylated bile salt derivatives: the role of steroid ring hydroxylation. AB - The hydroxyl groups of bile salts play a major role in determining their physical properties and physiologic behavior. To date, no fluorescent bile salt derivatives have been prepared which permit evaluation of the functional role of the steroid ring. We have prepared five fluorescent cholanoyl derivatives using a dansyl-ethylene diamine precursor linked to the sulfonyl group of taurine; N-(5 dimethylamino-1-naphthalenesulfonyl)-N'-(2-aminoethanesulf onyl)- ethylenediamine. The fluorescent dansyl-taurine was conjugated to the carboxyl group of free bile acids, enabling the labeling of the series: dehydrocholate, ursodeoxycholate, cholate, chenodeoxycholate and deoxycholate. Despite a systematic hydrophobic shift compared with the native bile salts (aqueous solubility and water:octanol partitioning), the influence of steroid ring hydroxylation was retained, with the dehydrocholate and cholate derivatives more water soluble than the dihydroxy derivatives. Similarly, the sequence of HPLC mobilities, reflecting relative hydrophilicity, was identical in the dansyl taurine derivatives and the native taurine-conjugated bile salts. Cellular uptake of all five steroid derivatives was rapid, and partial inhibition of [3H]taurocholate uptake was observed in isolated hepatocytes. Rates of biliary excretion of the dansylated derivatives by the isolated perfused rat liver correlated closely with hydrophilicity. Collectively, these findings indicate that the influence of the hydroxyl groups is retained in this series of dansylated steroids, and that hydroxylation is a key determinant of their hepatocellular transport and biliary excretion. These fluorescent bile salt derivatives may thus serve as unique probes for investigating structure-function relationships in hepatic processing of steroid-based compounds. PMID- 1892893 TI - Effect of 17 beta-estradiol on PAF and prostaglandin levels in oophorectomized rat uterus. AB - The effects of 17 beta-estradiol on the levels of platelet-activating factor (PAF) and prostaglandins and their precursor phospholipid in the uterus of oophorectomized rats were studied. Oophorectomy results in the decrease in the uterine PAF level to one-third of that in natural estrus. This level was recovered by subcutaneous administration of 17 beta-estradiol. The level of uterine phospholipids, which are rich in arachidonic acid, was significantly decreased by estradiol treatment. More arachidonate-PC was depleted than arachidonate-PE. The molecular structure was confirmed by gas chromatography-mass spectrometry. The amount of PGF2 alpha in the oophorectomized uterine tissue was 10-times that of PAF, but like the latter, increased 3-4 times on estradiol treatment. The chemical structures of PAF and PGF2 alpha formed on estradiol treatment were confirmed by mass spectrometry. The present data strongly suggest a correlation between the formations of PAF and PGF2 alpha, and indicate that estradiol may regulate the physiological formations of PAF and PGs in non pregnant rat uterus. PMID- 1892894 TI - Arachidonate 5-lipoxygenase of porcine pancreas: its localization in acinar cells. AB - Arachidonate 5-lipoxygenase has been found so far in various types of leukocyte. When a homogenate of porcine pancreas was incubated with arachidonic acid, 5 hydroxy-6,8,11,14-eicosatetraenoic acid was predominantly produced concomitant with small amounts of compounds derived from leukotriene A4. After differential centrifugation of the homogenate, the 5-lipoxygenase activity was found predominantly in the 1000 x g pellet and 105,000 x g supernatant. When porcine pancreas was investigated immunohistochemically with anti-5-lipoxygenase antibody, Langerhans islets were unstained, and infiltration of 5-lipoxygenase positive leukocytes was hardly observed. In contrast, acinar cells were positively stained. Immunoelectron microscopy demonstrated the localization of the enzyme along the nuclear membranes of the acinar cells. PMID- 1892895 TI - The role of palmitic acid in pulmonary surfactant: enhancement of surface activity and prevention of inhibition by blood proteins. AB - The surface activity of two surfactant preparations, Lipid Extract Surfactant (LES) and Survanta, was examined during adsorption and dynamic compression using a pulsating bubble surfactometer. At low surfactant phospholipid concentrations (1-2.5 mg/ml), Survanta reduces surface tension at minimum bubble radius faster than LES: however, with continued pulsation LES obtains a lower surface tension. Addition of surfactant-associated protein A (SP-A) to LES significantly reduces the time required to reduce surface tension. Survanta is completely unresponsive to the addition of SP-A in that no further reduction of surface tension is observed. Addition of various blood components has been previously shown to inactivate surfactants in vitro. Addition of fibrinogen to Survanta causes an increase in surface tension when measured in the absence of calcium. When assayed in the presence of calcium, inhibition by fibrinogen is not observed possibly due to aggregation of this protein. Albumin and alpha-globulin strongly inhibit Survanta at physiological serum concentrations both in the presence and absence of calcium. The surface activity of Survanta is also inhibited by lysophosphatidylcholine (lyso-PC). The role of palmitic acid in the surface activity of pulmonary surfactant was examined by adding palmitic acid to LES. At low phospholipid concentrations addition of palmitic acid (10% w/w of the surfactant phospholipid) greatly enhances the surface activity of LES. Maximal enhancement of surface activity and adsorption was observed at or above 7.5% added palmitic acid (w/w of surfactant lipid). LES supplemented with palmitic acid is more resistant to inhibition by fibrinogen, albumin, alpha-globulin and lyso-PC than LES alone, however, the counteraction of blood protein inhibition is not as pronounced as that observed with SP-A. PMID- 1892896 TI - Acyl-CoA: cholesterol acyltransferase in HT 29 cell subpopulations. Defect of activity in the undifferentiated cells. AB - The ACAT activity was studied on different subpopulations deriving from HT29 cells, a human colon carcinoma cell line. Grown on standard medium (25 mM glucose), about 95% of these cells are undifferentiated (G + cells). From this heterogeneous population, differentiated cells were selected by glucose deprivation and grown either on medium without glucose (G - cells) or in standard medium containing 25 mM glucose (G-Rev cells). The G- and G-Rev cells have the features of differentiated small intestine cells. The two types of differentiated cells (G- and G-Rev) exhibited similar ACAT activities and the kinetic characteristics of the enzyme were also similar. A time-course study showed increasing activity during the exponential phase and a decrease just after confluency. It was possible to stimulate the enzyme by micellar or lipoprotein cholesterol. In contrast, the ACAT activity was hardly detectable in undifferentiated G + cells. In addition, all the experimental conditions known to stimulate ACAT activity, and confirmed in the differentiated HT29 cells, were inefficient in the undifferentiated G + cells. Therefore, the different models derived from HT29 cells provide the opportunity to study cholesterol esterification as well as the consequences of its aberrances in intestinal cells. PMID- 1892897 TI - Absolute quantification of 31P muscle metabolites using NMRS with an internal standard and a high-Q, double-tuned coil. AB - 31P-nuclear magnetic resonance spectroscopy (NMRS) is used to determine absolute concentrations of 31P metabolites in rat muscle. A technique exploiting tissue water 1H as internal concentration reference and a highly sensitive, double-tuned coil is described and evaluated experimentally. On KH2PO4 solutions of known concentration and varying coil loading it is shown to allow neutralization of systematic errors due to conductive losses, which normally range up to 20% or more. In vivo application in the determination of the absolute concentrations of ATP, PCr and Pi in eight rat thighs yields results that are in good agreement with literature values. PMID- 1892898 TI - Effect of rat plasma high density lipoprotein with or without apolipoprotein E on the cholesterol uptake and on the induction of the corticosteroid biosynthetic pathway in newborn rat adrenocortical cell cultures. AB - High density lipoprotein (HDL) has been shown to induce the cellular accumulation of cholesterol esters and the biosynthetis of 21-hydroxysteroids (corticosteroids) newborn rat adrenocortical cells cultivated in serum-free medium. In order to identify the component(s) of HDL responsible for these effects, we investigated the ability of rat HDL subfractions and HDL with or without apolipoprotein E to deliver cholesterol to cells and to stimulate the steroid biosynthetic pathways in adrenal cultured cells. The total cholesterol uptake from HDL2 was greater than that observed with HDL rich in apolipoprotein E (HDL1 and HDLc). Furthermore, the increase of the ratio between 21 hydroxysteroids and reductive metabolites of progesterone was higher with HDL2 than with HDL1 or HDLc. The results of competitive studies between LDL and HDL subfractions indicate that adrenal cells take up cholesterol from HDL2 and LDL by separate mechanisms but that LDL and HDL containing apolipoprotein E share the same uptake processes. In experiments with various concentrations of HDLc or HDL without apolipoprotein E, the adrenal cells displayed a higher affinity for rat HDLc than for rat HDL without apolipoprotein E. However, HDL without apolipoprotein E produced a higher enhancement of the cholesterol cell content and was 3-fold more effective in stimulating 21-hydroxylated steroid production than rat HDLc. Although these findings suggest a participation of HDL with apolipoprotein E in the HDL interaction with rat adrenal cells, the predominant effect on these cells is devoluted to HDL containing mainly apolipoprotein A. PMID- 1892899 TI - Molecular basis of signal integration in phosphorylase kinase. PMID- 1892900 TI - ZK98299, a novel antiprogesterone that does not interact with chicken oviduct progesterone receptor. AB - Steroid antagonists, at receptor level, are valuable tools for elucidating the mechanism of steroid hormone action. We have examined and compared the interaction of avian and mammalian progesterone receptors with progestins; progesterone and R5020, and a newly synthesized antiprogesterone ZK98299. In the chicken oviduct cytosol, [3H]R5020 binding to macromolecule(s) could be eliminated with prior incubation of cytosol with excess radioinert steroids progesterone or R5020 but not ZK98299. Alternatively, [3H]ZK98299 binding in the chicken oviduct was not abolished in the presence of excess progesterone, R5020, or ZK98299. In the calf uterine cytosol, [3H]R5020 or [3H]ZK98299 binding was competeable with progesterone, R5020 and ZK98299 but not estradiol, DHT or cortisol. Furthermore, immunoprecipitation and protein A-Sepharose adsorption analysis revealed that in the calf uterine cytosol, the [3H]R5020-receptor complexes were recognized by anti-progesterone receptor monoclonal antibody PR6. This antibody, however, did not recognize [3H]ZK98299-receptor complexes. When phosphorylation of progesterone receptor was attempted in the chicken oviduct mince, presence of progesterone resulted in an increased phosphorylation of the known components A (79 kDa) and B (110 kDa) receptor proteins. Presence of ZK98299 neither enhanced the extent of phosphorylation of A and B proteins nor did it reverse the progesterone-dependent increase in the phosphorylation. The avian progesterone receptor, therefore, has unique steroid binding site(s) that exclude(s) interaction with ZK98299. The lack of immunorecognition of calf uterine [3H]ZK98299-receptor complexes, suggests that ZK98299 is either interacting with macromolecule(s) other than the progesterone receptor or with another site on the same protein. Alternatively, the antisteroid binds to the R5020 binding site but the complex adopts a conformation that is not recognized by the PRG antibodies. PMID- 1892901 TI - Glucose: a more powerful modulator of fructose 2,6-bisphosphate levels than insulin in human hepatocytes. AB - This study provides the first experimental evidence of the short-term control of fructose 2,6-bisphosphate (Fru(2,6)P2) levels in adult human hepatocytes. (1) In hepatocytes whose metabolic status resembles the fed state (glycogen-rich), exposure to glucagon (10(-8) M) caused a drastic decrease in the levels of this effector and a significant fall in lactate production rate. Adrenaline, isoprenaline (a beta-adrenergic agonist) and lactate exerted a similar action decreasing Fru(2,6)P2 concentration. (2) In glucagon pre-treated, glycogen- and Fru(2,6)P2-depleted cells (a situation that mimics the fasted state), Fru(2,6)P2 re-synthesis was strictly dependent on glucose availability. (3) Insulin did not seem to exert a direct action on the control of Fru(2,6)P2 in human hepatocytes. The hormone--which failed to enhance Fru(2,6)P2 in glucose-starved cells--did not further increase Fru(2,6)P2 content nor its time-course evolution as compared to hepatocytes incubated with glucose alone. (4) Lactate caused a significant delay in the glucose-induced increase in Fru(2,6)P2 content that could not be prevented by insulin. (5) Data indicate that in human hepatocytes glucose is a more powerful modulator of Fru(2,6)P2 than insulin, and that variations in blood lactate concentration may also play a role in the control of hepatic Fru(2,6)P2 levels during the fasted-to-fed transition in humans. PMID- 1892902 TI - [Assessment of conformation changes of immunoglobulin G molecules using a fluorescent probe]. AB - A proximate method for conformational changes detection in immunoglobulin G preparations used in research and medical practice is introduced. This method is based on the measurement of IgG-connected 1,8-anilinenaphtalenesulphonate fluorescent probe (ANS) time of damping. When the protein structure is broken fluorescence damping time of IgG-connected ANS rises up. PMID- 1892903 TI - [Binding of mitoxantrone and ametantrone with poly(d(G-C)) on the B---Z transition, stimulated by NaCl]. AB - Binding of antitumoral preparations mitoxantrone and ametantrone with right and left helical DNA was investigated. B-Z conformational transition stimulated by NaCl in the molecules of poly[d(G.C)].poly[d(G-C)] in complex with mitoxantrone and ametantrone was studied by the method of circular dichroism. It was shown that these compounds disturb B-Z transition but do not inhibit it. PMID- 1892904 TI - [Adsorption of human serum albumin on the original and albuminized surface of quartz]. AB - The method of TIRF is used for obtaining kinetic curves of HSA adsorption on coated and uncoated silica surfaces. Using the model of energetic heterogeneous surface an analysis of positive effect of passivation as a result of transformation of energetic heterogeneity of quartz surfaces from rectangular to exponential is performed. PMID- 1892905 TI - [Changes in membrane potential and transport of ions through the S. typhimurium LT2 membrane induced by bacteriophages]. AB - Bacteriophages P22 and dp8 cause the membrane potential depolarization for 10-30 mV, reversal rapid H+ influx into bacteria and K+ exit from S. typhimurium LT2, these effects depend on infection plural and are observed only in the presence of Ca+2 in the medium. delta psi depolarization and K+ efflux induced by phage dp8 are increased with the growth of Mg+2 concentration from 0 to 2 mM. Changes of delta pH and also Na+,Ca+2 concentrations are not observed. In the presence of glucose phage infection leads to changes in H(+)-K(+)-exchange. The phages P22 and dp8 adsorption on bacteria causes changes in the form or turn of the channels in S. typhimurium membrane. PMID- 1892906 TI - [Temperature changes of extracellular media state on a bacterial suspension]. AB - Within temperature intervals 30-40 degrees C for bacterial suspension of E. coli and 24-34 degrees C for B. flavum the extracellular medium exists in a specific state. Water in the extracellular medium is stabilized by increased hydrophobicity of extracellular protein molecules surface due to proteins conformational change. The total amount of UV-absorbing metabolites is decreased as a result of activation of microorganisms transport systems. The temperature intervals of these processes are different for both types of the microorganisms and coincide with their temperature optima of vital activity. PMID- 1892907 TI - [Calculating the diffusion coefficient in the eye lens]. AB - An experimental investigation of the appearance of a cataract under intensive irradiation is carried out. On the basis of the results obtained a model is proposed of calculating the diffusion coefficient which can model the crystalline lens, its individual peculiarities being taken into account. PMID- 1892908 TI - [Diffusion properties of water in the human crystalline lens during cataract development]. AB - Normal and cataractal decapsulated lenses of man were studied by NMR method-spin echo to obtain information concerning efficient coefficients of self diffusion, times of spin-spin relaxation of water protons (T2) and water content in the lens (c) at 25 degrees C in the course of cataractogenesis. It has been found that the values T2 and c at 25 degrees C are much higher in the nuclei of completely turbid lenses than in the transparent ones; the self-diffusion coefficients in the turbid lenses were also higher. At -9 degrees C a significant decrease of the content of undestroyed by frost (bound) water was observed at the stage of mature cataract as compared to transparent lenses. It is suggested that the most specific differences between the nuclei of transparent and completely turbid lenses are related to increased diffusion mobility of water molecules, apparently, at the expense of damaged plasmic membranes of the lens fibres noted during cataract development. PMID- 1892909 TI - [Simulated model of auto-associative memory in the form of a neural network with a low level of activity]. AB - Information parameters of the neuron net performing the functions of autoassociative memory were investigated by imitation modelling method. The fully connected network with Hebb gradual synapses was studied. Its information capacity was shown to increase significantly with a decrease of the activity level of the stored patterns. This evidence agrees well with the analytical result obtained earlier by the replica method. PMID- 1892910 TI - [Interconnection of wave processes for control and performance in the movements of multisegmental biomechanical systems]. AB - There are two main ideas in this work. First, speed and tonicity of contraction of different muscles in human movements are defined not only by specifications of the contraction apparatus, but also by specifications of the management apparatus functioning, which means a solution of the motor task. Second, the observed in human movement wave processes are the consequences of the wave processes in the systems regulating movements of different parts of the body. Some experimental data observed earlier are discussed in terms of the proposed ideas. PMID- 1892911 TI - [Do external or internal reasons determine the synchronicity of cell division at early stages of embryogenesis?]. AB - By the method of computer simulation the 2-dimensional diagram, which reveals the dependence of the degree of cell division synchronization on genetic variation and environment variety, was obtained. The diagram demonstrates many trajectories of the cell system self-organization. It was shown that synchronization on the early stages of loach spawn embryogenesis may be obtained by the combination of various internal and external factors. PMID- 1892912 TI - Carbachol stimulates a different phospholipid metabolism than nerve growth factor and basic fibroblast growth factor in PC12 cells. AB - We have examined 1,2-diglycerides (DGs) generated in PC12 cells in response to the muscarinic agonist carbachol and compared them with those generated in response to the differentiation factors nerve growth factor and basic fibroblast growth factor. Whereas carbachol stimulates a greater release of inositol phosphates, all three agonists generate similar levels of DGs. In this report, we have analyzed the molecular species of PC12 DGs generated in response to these three agonists. Additionally, we have analyzed the molecular species of PC12 phospholipids. The data indicate that 1) after 1 min of either nerve growth factor or basic fibroblast growth factor stimulation, DGs arise primarily from phosphoinositide hydrolysis; 2) in contrast, after 1 min of carbachol stimulation, DG are generated equally by both phosphoinositide and phosphatidylcholine hydrolysis; and 3) after 15 min of stimulation by any of these agonists, DGs are generated largely by phosphatidylcholine hydrolysis, with a smaller component arising from the phosphoinositides. These results suggest that at least part of the mechanism by which PC12 cells distinguish between different agonists is via alterations in phospholipid sources and kinetics of DG generation. PMID- 1892913 TI - Diagnostic imaging advances in neurooncology. AB - As we move into the 1990s, the field of diagnostic imaging displays greater usefulness as a result of continued technical improvements in existing modalities and the discovery of new techniques. Magnetic resonance (MR) imaging is now, without question, the imaging modality of choice for evaluation of tumors of the brain and spine. The general availability of the MR imaging contrast agent, gadolinium diethylenetriamine penta-acetic acid (Gd-DTPA), for the last three years has greatly expanded the role of MR imaging. Progress in metabolic imaging and MR spectroscopy may offer yet greater understanding of the physiology of brain tumors and has application for the diagnosis and posttreatment follow-up of these patients. These topics will be addressed in this review, which spans the years 1989 and 1990. PMID- 1892914 TI - Pathology and neuroepidemiology of the brain and nervous system. AB - The main contributions in 1990 to oncology of the nervous system in the fields of pathology and epidemiology are discussed in this review. In the area of pathology many articles are devoted to case series and to clinicopathologic correlations, especially for brain tumors in children, for which precise correlations are still lacking. Immunohistochemistry is widely represented in this year's literature and its contributions are directed primarily to the recognition of antigens or new antigens in the tumors, in order to reach a more appropriate classification of information on pathogenesis. Other problems were those of the relationship between angiogenesis and tumor invasion, the characteristics of tumor invasiveness, tumor immunology, host resistance, and molecular aspects. A number of papers have also been dedicated to cell kinetics and to the application of methods revealing the proliferation potential of tumors, to achieve a better prognostic formulation from biopsies. Epidemiologic studies continue to explore the incidence of tumors, especially in young patients, and the associations with exposures to different stimuli and immunosuppression. PMID- 1892915 TI - Neurosurgery issues in oncology. AB - Advances in the surgical management of central nervous system neoplasms have been reported in several areas including the skull base, the spine and the stereotaxic applications in neurosurgery. A national survey of patterns of care for brain tumor patients contributed data on 11,185 patients, 97% of whom underwent surgery. Stereotaxic-guided craniotomies are providing added accuracy and shortened operative time and length of hospitalization, while the stereotaxic implantation of I125 seeds for recurrent high grade glioma has resulted in prolongation of survival between 54 and 81 weeks. Radiosurgery is being applied with increasing frequency and remarkable success in the management of skull base tumors, acoustic neuroma, and brain metastasis. The two prototypes used are the Gamma-knife and the linear accelerator-based multiple converging arcs technique. In the area of the skull base, significant anatomical details have been provided. Historical facts and clinical series related to the management of meningiomas and acoustic neuromas are reviewed. Spinal cord ependymoma is a surgically curable tumor as reported in a series of twenty-three patients followed for a mean of 62 months, and a randomized study has established the superiority of surgical resection for single brain metastasis as compared to the results obtained with radiation therapy alone. PMID- 1892916 TI - Treatment of gliomas in adults. AB - Gliomas are the most common tumors in the brain and are almost always malignant in adults. The most malignant and most common glioma is glioblastoma multiforme. Median survival of patients with glioblastoma is less than 20 months following treatment. This poor prognosis reflects the limited efficacy of the currently available treatment modalities. Therefore, many attempts have been made to improve the treatment of this lethal disease. This paper reviews the progress that has been made recently in the treatment of malignant glioma with a focus on studies reported during the last year. PMID- 1892917 TI - Neuroblastoma, retinoblastoma, and brain tumors in children. AB - Considerable progress has been made recently in the biologic understanding and the clinical management of pediatric tumors of the peripheral and central nervous system. Here we review important representative studies published primarily in the past 2 years regarding neuroblastoma, retinoblastoma, and brain tumors in children. Highlights include 1) the importance of tumor DNA content, N-myc amplification, and chromosome 1 deletion in predicting outcome of patients with neuroblastoma; 2) the impact of mass screening for neuroblastoma in Japan and elsewhere; 3) improvements in the clinical management of neuroblastoma, retinoblastoma, and brain tumors; and 4) neurologic sequelae of these tumors and their treatment. PMID- 1892918 TI - Experimental head and neck oncology. AB - Recent research, both clinical and basic, has focused intensively on specific areas within head and neck oncology. The impetus for such efforts is enhanced by reports documenting a growing incidence of the disease. Thus, areas such as genetic determinants of head and neck cancer progression become a more pressing issue. Furthermore, studies that include both cytogenetic and molecular analyses emphasize cancer heterogeneity. In the field of tumor biology, newly developed animal models also demonstrate the multiplicity of cancer properties. The capacity to define these characteristics within a patient's respective cancer would allow a more targeted approach to cancer therapy. Finally, research efforts have focused on the problem of second primary cancers. To prevent metachronous tumors would have broad implications in the elimination of environmentally induced diseases. PMID- 1892919 TI - Pathology of squamous carcinomas of the head and neck. PMID- 1892920 TI - Diagnostic radiology of head and neck oncology. AB - The rapid development of computed tomography and magnetic resonance imaging has resulted in numerous applications of these modalities in head and neck oncology. In the past year further refinements in diagnostic capabilities have been obtained in magnetic resonance imaging. Computed tomography is rapidly being replaced by magnetic resonance imaging as the study of choice in the majority of lesions in the larynx, pharynx, tongue, paranasal sinuses, and parapharyngeal space. Magnetic resonance imaging, ultrasound-guided fine-needle aspiration cytology, and in potential radioimmunolocalization of cancer deposits by monoclonal antibodies have great value for the detection of lymph node metastasis in the neck. Because more effective locoregional treatment has been developed, there is an increasing interest in the early diagnosis of distant metastases. The value of new technologies such as three-dimensional imaging and spectroscopy for imaging of primary tumors must be assessed. PMID- 1892921 TI - Surgical treatment in head and neck cancer. AB - Three topics currently important in head and neck surgery are voice-conserving surgical treatment of laryngeal cancer, the role of modified radical neck dissection in the treatment of cervical metastases, and reconstruction and rehabilitation of the head and neck cancer patient. The laser has become an accepted modality for the treatment of early vocal cord cancer and has local control rates comparable to other treatment methods. Partial laryngectomy can conserve voice and yield excellent local control rates. The modified radical neck dissection has been shown to yield rates of local recurrence no greater than radical neck dissection for N0 and N1 neck disease associated with laryngeal cancer. Vocal rehabilitation following total laryngectomy has been revolutionized by the tracheoesophageal puncture procedure. Most patients can be expected to acquire voice using tracheoesophageal puncture following total laryngectomy. Free flaps have improved the functional results of many major head and neck surgical procedures and offer the possibility of better results in the future. However, more conventional reconstructive techniques, including local flaps, continue to have a role in head and neck surgery. PMID- 1892922 TI - Progress in radiotherapy by treatment tailoring in head and neck cancer. AB - Radiotherapy plays a key role with surgery in the treatment of head and neck cancer. Encouraging results have recently been published indicating new ways to improve locoregional control by tailoring the radiation treatment to individual tumors. This has been reached by the following means: adapting fractionation schemes to the potential doubling time of tumors, technical developments resulting in higher doses to the primary tumor and at the same time reducing normal tissue doses, and the concomitant use of radiotherapy and chemotherapy. Fractionation studies have shown that changing the standard fractionation schedule can increase the therapeutic margin of radiotherapy. Predictive assays are now becoming available to provide guidelines for the optimal fractionation schedules in individual patients. Combined treatment with radiotherapy and chemotherapy has been widely tested and although the results have been generally disappointing, one approach remains promising, ie, the concomitant use of these two modalities, which seems to result in a modest improvement of survival. Increasing the radiation dose to the tumor together with a better shielding of normal tissues has become possible by technical developments in radiotherapy such as three-dimensional treatment planning, multileaf collimators, and quality control procedures using megavoltage imaging devices. PMID- 1892923 TI - Chemotherapy and integrated treatment approaches in head and neck cancer. AB - Chemotherapy continues to be studied intensively in head and neck cancer. Methotrexate and cisplatin remain standard agents for patients with recurrent disease. Neoadjuvant chemotherapy remains investigational with no firm evidence that it can prolong survival. It may, however, have a role in organ preservation. More recent and aggressive neoadjuvant chemotherapy regimens remain to be tested in randomized studies. Concomitant chemoradiotherapy is of high interest in this disease and is of proven benefit in randomized trials. Encouraging data from trials using protracted radiation schedules will require confirmation in randomized studies. PMID- 1892924 TI - Penile and adrenal cancer. AB - The existing hypothesis of a viral etiology of penile cancer has been further supported. Exposure to ultraviolet radiation might be another etiologic factor. Controversies still exist as to whether immediate or delayed inguinal lymphadenectomy should be performed in all patients or only in those who are at high risk for developing metastases (histologic dedifferentiation, vascular invasion). 5-Fluorouracil, cisplatin, bleomycin, and methotrexate are active cytostatic drugs in penile cancer and may have a role in the multimodality treatment of this condition. The sensitivity of abdominal computed tomography in detecting adrenal tumors is reported to be 20% to 41%, and the specificity, 85% to 99%. Immunohistopathology may facilitate the differential diagnosis between malignant and benign adrenal cortical tumors. In a retrospective analysis of 105 patients with adrenal cortical cancer, the overall 5-year survival was 22%. Seventy-nine percent of the tumors were hormone producing. Mitotane yielded biochemical and objective responses without impact on survival. PMID- 1892927 TI - Head and neck oncology. PMID- 1892926 TI - Brain and nervous system. PMID- 1892925 TI - Prostatic cancer: where do we go from here? AB - This paper focuses on advances in prostatic cancer that occurred during the past year. Specific areas reviewed here are screening, radical surgery, locoregional disease, the no-therapy option, androgen-ablative therapy, prognostic factors, bone-specific therapy, hormone refractory disease, and prostate cancer biology. PMID- 1892928 TI - Genitourinary system. PMID- 1892929 TI - In vitro antimicrobial susceptibility of Pasteurella haemolytica and Pasteurella multocida recovered from cattle with bovine respiratory disease complex. AB - The antimicrobial susceptibilities of 421 Pasteurella haemolytica and 158 P. multocida isolates recovered from cattle with respiratory disease were determined with a microdilution minimal inhibitory concentration test system. Isolates were analyzed for patterns of resistance to ampicillin, ceftiofur, erythromycin, gentamicin, penicillin, spectinomycin, sulfachlorpyridazine, sulfadimethoxine, tetracycline, and tylosin. All isolates tested were found susceptible to ceftiofur and sulfachlorpyridazine. Pasteurella haemolytica isolates were resistant to ampicillin, penicillin, sulfadimethoxine, tetracycline, and tylosin. Pasteurella multocida isolates were resistant to sulfadimethoxine, tetracycline, and tylosin. PMID- 1892930 TI - Comparison of in vitro replication and cytopathology caused by strains of canine distemper virus of vaccine and field origin. AB - Three biological properties of canine distemper virus were examined to determine if any would consistently differentiate field from vaccine strains of the virus. The properties were the ability to (1) infect macrophages and epithelial cells, (2) produce distinct cytopathologic effect in alveolar and peritoneal macrophages and Vero cells, and (3) produce pocks on the chorioallantoic membrane of embryonated chicken eggs. Four vaccine strains and 5 field isolates were used in the study. The 5 field isolates were obtained directly from canine tissues. Of the 3 properties studied, only the comparison of the ability of the viruses to infect macrophages and epithelial cells was a consistent marker of virus origin. Virulent field isolates would only infect macrophage cultures, whereas the vaccine strains infected both types of cells. One avirulent field isolate from a case of old dog encephalitis reacted more like a vaccine strain by infecting both cell types. PMID- 1892931 TI - Diagnosis and prevalence of leptospira infection in aborted and stillborn horses. AB - A study was conducted to evaluate a recently available fluorescent antibody test (FAT) conjugate for the detection of leptospires in tissues of aborted and stillborn horses, to determine the leptospira antibody titers and compare serologic test results with FAT results, and to determine the prevalence of leptospira-induced abortions and stillbirths in the equine population of central Kentucky. From July 1, 1988 through June 30, 1989, 15 (2.5%) of 594 submissions (fetuses, stillborn foals, and/or placentas) were diagnosed as leptospirosis by the FAT (14 of 15 tested) and/or microscopic agglutination test (12 of 14 tested). Of the 12 serologically positive fetal fluids, 10 had high tigers against Leptospira interrogans serovar pomona and 2 against serovar grippotyphosa. PMID- 1892932 TI - Reproductive failure associated with Leptospira interrogans serovar bratislava infection of swine. AB - Specimens from 17 swine herds experiencing reproductive failure were examined for Leptospira interrogans serovar bratislava. Clinical signs observed in these herds included stillborn pigs, weak neonatal pigs, and abortion. Diagnostic tests used to determine L. interrogans serovar bratislava infection were bacteriologic culture, serologic assays to detect antibodies, and immunofluorescence. Examination of fetal serum for antibodies against serovar bratislava and a fluorescent antibody test were the most practical diagnostic procedures. PMID- 1892934 TI - Copper toxicosis in veal calves. AB - Copper toxicosis was diagnosed in 7 veal calves, 10-16 weeks old, from 5 separate farms. All calves died without specific clinical signs, although 4 of the calves were icteric. The calves' dietary rations had been supplemented with various copper-containing hematinics. Peritoneal hemorrhage was reported at post-mortem in 2 calves. Microscopic evidence of hepatopathy consisted of hepatocellular degeneration and necrosis, hemorrhage, and fibrosis. Concentrations of copper in livers from intoxicated calves ranged from 277 to 684 ppm and in kidneys from 1.1 to 82.0 ppm. The extent and severity of lesions in livers appeared to correlate with concentrations of copper. Nephrosis was minimal, without evidence of hemoglobinuria. PMID- 1892935 TI - Influence of inoculum volume in diagnosis of environmental mastitis from clinical quarters. PMID- 1892933 TI - Cocontamination of swine diets by aflatoxin and diacetoxyscirpenol. AB - The effects of dietary aflatoxin (AF) and diacetoxyscirpenol (DAS), singly and in combination, were evaluated in growing crossbred barrows. The experimental design consisted of 4 treatments of 9 barrows each fed diets containing 1) 0 mg AF and 0 mg DAS/kg feed (control), 2) 2.5 mg AF/kg feed, 3) 2.0 mg DAS/kg feed, or 4) 2.5 mg AF + 2.0 mg DAS/kg feed for 28 days (10-14 weeks of age). Production performance, serum biochemical, hematologic, and pathologic measurements were made. Body weight and body weight gain were significantly decreased by each toxin but more so by the combination treatment. The effects were additive in nature. Liver and spleen weights, as percentages of body weight, were increased by the AF and AF + DAS treatments, and AF or AF + DAS treatments induced diffuse hepatocellular vacuolar change, early portal fibrosis, and early bile duct hyperplasia. Aflatoxin increased serum values of creatinine and gamma glutamyl transferase, cholinesterase, and alkaline phosphatase activities; increased packed cell volume and hemoglobin; and decreased urea nitrogen and total iron binding capacity. DAS reduced serum iron binding capacity. The AF + DAS treatment increased serum gamma glutamyl transferase and alkaline phosphatase activities, increased hemoglobin, and decreased serum iron binding capacity. Generally, the combination treatment could be described as additive or less than additive, with most of the effects attributable to AF. Under the conditions and parameters monitored in this study, AF and DAS had no synergistic toxic effects when incorporated into diets of growing barrows. PMID- 1892936 TI - Fatal toxoplasmosis in some native Australian birds. PMID- 1892937 TI - Susceptibility of Streptococcus suis to penicillin. PMID- 1892938 TI - Lupin bean meal toxicosis in swine. PMID- 1892939 TI - Observations on the occurrence of Pasteurella testudinis in clinical specimens from animals. PMID- 1892940 TI - Spinal cord ischemic necrosis due to fibrocartilaginous embolism in a horse. PMID- 1892941 TI - Photosensitization outbreak in shorthorn calves in Missouri. PMID- 1892942 TI - Senate committee investigates medical equipment: opportunities for ET nursing. PMID- 1892943 TI - Pressure ulcer prevention and early treatment. PMID- 1892944 TI - Role of the ET nurse in the management of incontinence. PMID- 1892945 TI - A clinical study of hospital replacement mattresses. PMID- 1892946 TI - A pilot study of interface pressure with heel protectors used for pressure reduction. PMID- 1892947 TI - Conceptualization of the stage 1 pressure ulcer. PMID- 1892949 TI - Fecal incontinence. PMID- 1892948 TI - Collaboration and resourcefulness in ureterostomy care for the visually impaired: a case study. PMID- 1892950 TI - [Modification of the phospholipid composition of the cardiomyocyte sarcolemma in izadrin-induced myocarditis]. AB - A modification of phospholipid composition in rat cardiomyocyte sarcolemma occurring during isadrin myocarditis has been investigated. The fractions of sphingomyelin (SphM), phosphatidylserine (PhS), phosphatidylinositol (PhI), phosphatidylcholine (PhCh), phosphatidylethanolamine (PhEA) have been isolated. The shifts in phospholipid composition during isadrin myocarditis expressing in increase of the amount of choline-containing (PhCh + SphM) and decrease of acid (PhS + PhI) phospholipids have been revealed. During the isadrin myocarditis the incorporation of DL-[3-14C] serine in the fraction of total protein increases and in the fraction of total lipids decreases. The maximum incorporation of the label into total lipids in normal occurs faster than in case of myocarditis. The dynamics of the label distribution between metabolically related PhS, PhEA and PhCh indicates that PhS is the precursor of PhEA, the later being the precursor of PhCh. The label redistribution between PhS, PhEA and PhCh occurs by the sequence of metabolic transformations and by the direct base-exchange reactions. The intensity of the latter has been estimated by the incorporation of radioactive serine into phospholipids of the sarcolemma in vitro. The data obtained demonstrate the inhibitory action of isadrin myocarditis. PMID- 1892951 TI - [The effect of amino acid substitutions on the 3-dimensional structure of fragment 1--16 of the oncoprotein p21 ras]. AB - Using the method of theoretical conformational analysis, spatial structure of fragment 1-16 of active [( Val12-Gly13], [Asp12-Gly13], [Gly12-Asp13]) and passive [( Gly12-Gly13] and [Pro12-Gly13]) modifications of oncoproteins family p21 ras have been investigated. The activation of these proteins has been shown to be accompanied by reorganization of three-dimensional structure of the polypeptide chain. PMID- 1892952 TI - Liver fibrosis: perspectives in pathobiochemical research and clinical outlook. AB - Disturbances of the equilibrium between parenchyma and extracellular matrix, leading to a disproportionate increase in and an irregular deposition of newly formed connective tissue components (fibrosis), is a common sequel of chronic active liver diseases with serious clinical consequences. Significant progress has been made in recent years in the analysis of the structural composition of extracellular matrix in normal and fibrotic liver and in the dissection of the molecular and cellular mechanisms of exaggerated extracellular matrix deposition in necroinflammatory areas. Under the influence of inflammatory stimuli, perisinusoidal, retinoid-storing cells (Ito cells, parasinusoidal lipocytes), which are qualitatively and quantitatively the most important connective tissue producing cell type in human and animal liver, transform to myofibroblast-like cells. Activation and transformation of perisinusoidal cells are mediated by paracrine and autocrine loops involving transforming growth factor beta as the main fibrogenic mediator, which is secreted by activated liver macrophages, possibly also by endothelial cells, and liberated by disintegrated thrombocytes. The molecular and cellular interactions during liver fibrogenesis have become a model for a number of other organ fibrotic processes, wound repair and even atherogenesis. Therapeutic interference with the early steps of fibrogenesis seems feasible but a breakthrough has not yet been achieved. For clinical chemical, non-invasive diagnosis and monitoring of ongoing fibrogenesis, a rather limited repertoire of more or less organ- and disease-unspecific parameters is available. Split products of the extracellular maturation pathway of the procollagen types, laminin and hyaluronan, can be assayed but the clinical interpretation of the results has to be made with caution. Strategies and major topics of future pathobiochemical and clinically oriented research are highlightened. PMID- 1892953 TI - Deficiency of porphobilinogen synthase associated with acute crisis. Diagnosis of the first two cases in Chile by laboratory methods. AB - Erythrocyte porphobilinogen synthase deficiency was confirmed by the determination of its activity in blood and also by the high levels of both porphyrins and 5-aminolaevulinic acid in the urine of two siblings. They presented with a picture of porphyric attack characterized by abdominal colic pain, high blood pressure, tachycardia and severe constipation. The profile of both porphyrins and their precursors in urine and blood resembled lead poisoning. However, this was ruled out because both patients had normal blood levels of lead. Furthermore, porphobilinogen synthase activity did not normalize when it was determined in the presence of dithiothreitol or dithiothreitol plus zinc chloride. No other causes to account for a deficiency in porphobilinogen synthase activity were identified. The simultaneous occurrence of similar clinical and biochemical symptoms suggests that the same triggering factor was present. Because the activity of porphobilinogen synthase was less than 4% of normal values, it is possible that these patients were homozygotes with respect to this defect, which could explain the presence of clinical symptoms. We propose that this metabolic defect is not uncommon and it should be kept in mind when diagnosing of porphyrias or heavy metal intoxications. PMID- 1892954 TI - Isolation of restrictible DNA. AB - A simple method for the isolation of pure and high-yield DNA from whole blood, suitable for restriction enzyme digestion, is described. The steps of the procedure are as follows: cell lysis with NH4Cl, NaHCO3, EDTA; digestion with proteinase K in the presence of SDS; extraction with phenol-chloroform-isoamyl alcohol; and precipitation with ethanol. The 260 nm/280 nm absorbance ratio showed a mean value of 2, and the average yield of DNA was 212 micrograms/l. Such DNA preparations were found to be quite suitable for digestion by a variety of restriction endonucleases, as well as for the analysis of gene disorders by different biological methods. The method proposed appears to be useful in clinical chemistry laboratories. PMID- 1892955 TI - Evaluation of the automated haematology analyser Sysmex NE-8000. AB - The automated haematology analyser Sysmex NE-8000 was compared with the Technicon H-1, the automated analyser routinely used in our laboratory, and with manual cell differentiation results. One hundred and seventy samples from the daily routine workload, comprising specimens from healthy adults and patients with various ailments, were analysed on the Sysmex NE-8000 and the Technicon H-1. A manual-400 leukocyte differential count was performed on each specimen. Comparison of the results from the two blood cell counters showed good correlation (r greater than 0.9) for the white blood cell count, haemoglobin, haematocrit and platelet count. For the red blood cell count and mean cellular volume, the correlation coefficients were greater than 0.8. In the leukocyte differential count, Sysmex NE-8000 and Technicon H-1 showed good correlations for the neutrophil (r = 0.953), lymphocyte (r = 0.763), and eosinophil counts (r = 0.904). Correlation coefficients were very low for monocyte (r = 0.130) and basophil counts (r = 0.006). Correlation between the manual-400 method and the electronic leukocyte differential count showed similar results. Two hundred and twenty six normal and abnormal samples were compared with respect to morphology flagging with the two analysers, using the manual differentiation as the reference method. The abnormal specimens were representative of the range of leukocyte abnormalities seen in our laboratory. Sensitivity for detecting blasts was equal for both analysers. Sysmex NE-8000 was much more sensitive for detecting immature granulocytes than Technicon H-1. Low ranges of atypical lymphocytes were missed by Sysmex NE-8000. Left shift was also frequently missed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1892956 TI - Radioisotopic carnitine assay using Dowex 50 cation exchanger resin. AB - At termination of the known radioisotopic carnitine assay the incubating mixture was applied to a column of Dowex 50 W x 8 (H+) resin. The [1-14C]acetyl-L carnitine formed during the incubation bound to the resin, while the excess of [1 14C]acetyl-CoA was washed out with water. Then the radioactivity from the resin was eluted with NH4OH and water into counting vials. The assay is handy, takes much less (one-eights) resin than the known radioisotopic methods and the blank value is insensitive to sample volume. PMID- 1892957 TI - Sleep and sexual function in the elderly male. PMID- 1892958 TI - Aging, sleep disorders, and male sexual function. AB - The relation between age, sleep disorders, nocturnal penile tumescence, and sexual behavior was investigated in 70 healthy married men aged 45-75 years. They had an extensive psychosexual interview, a medical and psychiatric evaluation, and were studied in the sleep laboratory for four nights. Electroencephalogram (EEG), eye movements, muscle tone, and penile tumescence were monitored continuously, and respiratory airflow and bilateral anterior tibialis recordings were obtained during the first sleep session. There was a marked age-related increase in sleep-disordered breathing, but no significant changes in periodic leg movements with age. Respiratory distress and periodic leg movement (PLM) indices were mostly unrelated with nocturnal penile tumescence (NPT) measures as well as with all sexual behavior dimensions when age was taken into account in the analysis of results. Men with a respiratory distress disorder did not differ from a nondisordered group of similar age in NPT and behavioral parameters. Men with PLM disorder differed from their comparison group in only two variables: fewer number of maximum tumescent episodes and less frequent sexual thoughts. Men who met criteria for erectile impotence did not differ significantly in degree of respiratory or PLM disturbances or in the prevalence of sleep disorders when compared to an aged-matched sexually nondysfunctional group. The overall results did not support the notion that sleep disorders are involved in the increased prevalence of erectile impotence in healthy older individuals. Assessment of blood oxygenation and respiratory effort, in addition to airflow, need to be carried out before final conclusions can be drawn on the significance of sleep disordered breathing in male sexuality. PMID- 1892959 TI - 24-hour cortisol measures in adolescents with major depression: a controlled study. AB - Plasma cortisol levels were determined every 20 min for 24 hr in depressed adolescents (n = 27) meeting research diagnostic criteria (RDC) for major depressive disorder (MDD) and normal controls (n = 32). All subjects were between 12 and 18 years of age, at least Tanner Stage III of sexual development, medically healthy, and medication free at the time of the studies. The results showed that cortisol secretory patterns were very similar between the two groups with the exception that the depressed adolescents showed significantly elevated cortisol levels around sleep onset (a period when cortisol is usually suppressed). Subgroup analyses showed that most of these differences were contributed by the suicidal/inpatient depressed adolescents. The cause of the elevated cortisol during the normally quiescent period warrants further investigation and may be related to other biological disturbances around sleep onset (difficulty initiating sleep, reduced rapid eye movement (REM) latency, and alterations in sleep-stimulated growth hormone secretion). PMID- 1892960 TI - Circadian patterns of cortisol, prolactin, and growth hormonal secretion during bingeing and vomiting in normal weight bulimic patients. AB - Women who are of normal weight and have bulimia nervosa exhibit multiple neuroendocrine disturbances. We hypothesized that bingeing and vomiting behavior could be contributory because food consumption in healthy volunteers increases plasma cortisol and prolactin secretion and suppresses growth hormone secretion. Thus, we investigated the effects of bingeing and vomiting on the circadian pattern (measurements every 20 min for 24 hr) of these hormones in comparison to healthy control women eating normally. Bingeing and vomiting were associated with modest increases in cortisol and prolactin and reductions in growth hormone secretion. However, this bingeing or purging did not alter mean 24-hr pattern of cortisol and growth hormone secretion as values for bulimics were similar to controls. While mean daytime patterns of prolactin secretion were similar in bulimics and controls, bulimic patients had a significant reduction of nocturnal prolactin levels. In summary, bingeing and vomiting does not appear to have a substantial influence on hormonal secretion. However, bulimic women have blunted nocturnal prolactin patterns. PMID- 1892961 TI - Polysomnographic characteristics of healthy elderly subjects with somnambulism like behaviors. AB - We compared the sleep characteristics of seven healthy elderly people complaining of nocturnal somnambulism-like behaviors with those of 14 age-matched healthy elderly people who had never shown such behavior. Polysomnographic data revealed the appearance of "Stage 1-REM with tonic electromyographic (EMG) activity" sometimes accompanied by abnormal behavior in the first group, but the sleep architecture and parameters showed no significant difference between the two groups except for higher REM density in the first group. "Stage 1-REM with tonic EMG," observed in the first group was considered equivalent to REM sleep without muscle atonia. It is suggested that both reduced activity of tonic phenomena (muscle atonia) and increased activity of phasic phenomena (higher REM density) of REM sleep are essential for the induction of somnambulism-like behaviors during sleep in healthy elderly subjects. PMID- 1892962 TI - Lactate vulnerability after alprazolam versus placebo treatment of panic disorder. AB - Thirty-six patients with panic disorder underwent sodium lactate infusion before and after 8 weeks of treatment with alprazolam or placebo. With reinfusion, those patients panic-free with chronic alprazolam treatment displayed significantly decreased reactivity to lactate, as measured by subjective symptom ratings, duration of infusion before developing peak lactate-induced symptoms, and the proportion of patients experiencing lactate-induced anxiety or panic. Patients panic-free on placebo, as well as nonresponders to alprazolam treatment, displayed some, although less striking, decreases in reactivity to lactate with reinfusion. As a group, patients clinically unchanged with placebo treatment showed no systematic change in lactate response with reinfusion. Although the small numbers of patients in each treatment outcome group prohibit drawing definitive conclusions, these findings suggest that decreases in lactate-induced panic after successful alprazolam treatment of panic may result from a combination of changes in clinical state and direct effects of the medication. PMID- 1892964 TI - Subtype diagnosis in schizophrenia and its relation to neuropsychological and computerized tomography measures. AB - We compared schizophrenic patients with a subtype diagnosis of paranoia (n = 14) to those with nonparanoid subtype diagnoses (n = 18) on the Wisconsin Card Sorting Test (WCST) and multiple computed tomography (CT) scan measures. The results showed that patients with nonparanoid diagnoses sorted fewer categories and made more perseverative errors on the WCST than did patients with the paranoid diagnosis. However, patients in the nonparanoid group could not be distinguished from those in the paranoid group on CT scan measures of brain structure. Additionally, a significant correlation was found between right frontal sulcal enlargement on CT scans and the number of perseverative errors made on the WCST. PMID- 1892963 TI - Response of depression to very high plasma levels of imipramine plus desipramine. AB - Forty-five depressed patients were treated with imipramine for 6 weeks. Seven of 7 patients (100%) who had plasma levels of imipramine plus desipramine greater than 500 ng/ml showed a 50% or greater improvement in Hamilton depression scores compared with 23 of 38 patients (60%) with plasma levels less than 500 ng/ml (p less than 0.057). PMID- 1892965 TI - Buspirone alone or with serotonergic diet reduced aggression in a developmentally disabled adult. PMID- 1892966 TI - [Anesthesia morbidity and mortality. A plea for intensifying risk research]. PMID- 1892967 TI - [Anesthesia-related morbidity and mortality]. AB - Anesthesia-related mortality rate is estimated at 1 death per 10,000 procedures. Four general failures in anesthesia management are responsible for the majority of deaths: difficult intubation, aspiration, insufficient ventilation, and insufficient volume substitution. More than half of all critical incidents are considered preventable--by better patient preparation, better monitoring or increased vigilance. One in ten patients complains of simple complications such as nausea, vomiting, or a sour throat. In addition, 10% of all patients experience intra- or postoperative complications such as arrhythmia, hypo- or hypertension. Several patient-related factors, such as age or the number of coexisting diseases, as well as management factors, such as choice of anesthetic technique or the experience of the anesthesiologist, are important determinants of morbidity and mortality. This review gives a comprehensive summary of recent results in risk-analysis and the study of critical incidents in anesthesia. PMID- 1892968 TI - [Carbomonoxyhemoglobin and methemoglobin in patients with and without a smoking history during ambulatory anesthesia. Consequences for the use of pulse oximetry]. AB - Carboxyhemoglobin (COHb) and methemoglobin (MetHb) in venous blood were determined by oximetry in 1000 non-hospitalised preoperative patients. 370 of them were smokers (S), 630 non-smokers (NS). In addition, in five S we compared the oxygen saturation measured by pulse oximetry (SaO2, p) with that measured by in vitro oximetry (SaO2) and that calculated with reference to COHb (SaO2,korr). MetHb (0.66 +/- 0.21%, mean +/- standard deviation) was found to be of no relevance. COHb in S (5.12 +/- 2.25%, maximum 12.4%) was significantly higher than in NS (1.82 +/- 0.3%, range 0.9%-4.0%) and is therefore of importance in S for the oxygen transport and for the interpretation of SaO2, p, which overestimated SaO2 at a COHb level of 4.4 +/- 0.7% by 4.5 +/- 0.9%. The difference between SaO2, korr (calculated according to Forstner) differed from SaO2 by 0.66 +/- 0.5% only. We conclude that there is an indication for in vitro oximetry in non hospitalised smokers or cases of unknown smoking history. If oximetry is not available, both a reduction of O2-binding hemoglobin and an overestimation of SaO2 by pulse oximetry in an order of ten per cent should be taken into account. To compensate for dyshemoglobin fractions, pulse oximetry using more than two wavelengths is desirable. PMID- 1892969 TI - [The provision and perioperative transfusion of erythrocyte concentrates]. AB - A previously used order schedule for procuring blood concentrates was reviewed, as the need for blood had changed due to the application of blood saving methods. Furthermore, the indication to blood transfusion has been reduced as a result of the potential danger of infection with AIDS. In 1035 patients, we compared the number of preoperatively ordered with the number of perioperatively transfused units of blood. In addition, we documented the factors which lead to increased blood ordering. The relation between ordered and transfused units of blood in total was 596/97 (Urology: 392/78, Gynaecology: 179/18, ENT and Ophthalmology: 25/1). Anticoagulation, anaemia, secondary illnesses and specific surgical problems have been identified as factors leading to increased blood ordering. As to many units of blood are being crossmatched without being transfused, we developed a revised blood ordering schedule. According to this schedule for certain surgical procedures typing and screening only should be done rather than crossmatching. PMID- 1892970 TI - [Artificial respiration in the prone position in a case of acute respiratory distress syndrome]. AB - A patient is presented in whom an acute respiratory distress syndrome (ARDS) developed after severe lung contusion. Exchange of gas was markedly restricted under aggressive respiration (FiO2 = 1.0, PEEP = 10 mmHg, breathing time quotient = 0.5, respiratory minute volume = 16 litres; gas exchange values: PaO2 = 67 mmHg, PaCO2 = 45 mmHg, PA-aO2 = 461 mmHg). After control of the computed tomogram of the lungs showed marked densifications in those parts of the lung that are lower most by gravitation according to the positioning of the patient at a particular time the patient was ventilated in ventricumbent (prone) position for 60 hours. After having remained in this position for 48 hours, there was a significant improvement in the gas exchange (PaO2 = 89 mmHg, PaCO2 = 36 mmHg, PA aO2 = 77 mmHg at FiO2 = 0.3, PEEP = 6 mmHg, breathing time quotient = 0.5 and respiratory minute volume = 9 litres). The control CT in dorsal position showed that the dorsal densifications had disappeared completely. Five days later the patient could be extubated. Respiration in ventricumbent (prone) position may considerably improve oxygenation by perfusion of well-ventilated regions of the lung that are lower-most by gravitation according to the relative positioning of the patient. Besides regions not well ventilated or not ventilated at all (according to the patient's position) may be better ventilated or re-opened and made accessible to ventilation by this method. PMID- 1892971 TI - [Cardiac adverse effects following an intravenous injection of pirenzepine are an expression of deficient receptor sensitivity]. AB - Under the aspect of life-threatening pneumonias in long-term ventilated patients receiving ant-acids or H2-antagonists the prophylaxis of stress ulcer with pirenzepine gains new importance. This study was aimed at detecting cardiac side effects of pirenzepine due to low receptor specificity. Pirenzepine (10 mg) was given via the peripheral or central venous route at an injection velocity of 5 or 30 seconds as well as a control of 2 ml normal saline solution via the central venous route for 5 seconds, 20 times each. Heart rate and blood pressure were determined before and after the injection. Independent of the injection site or velocity, an increase in the heart rate was found after the injection of pirenzepine. The increase was more marked if the central venous route was used. The percentage rise in heart rate was up to the thirteenth minute highly significant when comparing pirenzepine to normal saline solution. There were no changes in blood pressure. If M1-cholinoceptors are blocked, a reduction of the heart rate is seen. Blocking M2-cholinoceptors causes a rise in the heart rate. Injecting 10 mg of the M1-antagonist pirenzepine results in a significant increase in the heart rate, independent of site or velocity of injection which can be explained by blocking M2-cholinoceptors at the same time. To prevent this probably dose-dependent effect, pirenzepine should be given slowly over a couple of minutes. PMID- 1892972 TI - [The economic aspects of autologous blood transfusion using a prosthetic hip joint replacement as an example]. PMID- 1892973 TI - [The concept of autologous transfusion from the viewpoint of the cost carrier]. PMID- 1892974 TI - [Autologous blood transfusion in general surgery]. PMID- 1892975 TI - [The critical hematocrit from the clinical point of view]. PMID- 1892976 TI - [Retransfusion in bone surgery: what happens to the fat?]. PMID- 1892977 TI - [A fatal bleeding complication following central venous catheterization in end stage pancytopenia. Medical and legal consequences]. AB - An attempt to insert a central venous catheter into the internal jugular vein of a patient suffering from pancytopenia failed and due to massive bleeding into the cervical tissue the patient developed severe dyspnoea and died during unsuccessful endotracheal intubation. A five-year judicial inquiry finally discharged the anaesthesiologist revealing that forensic aspects like a valid patient's consent, exact documentation of operations and therapies, clear arrangement with patient's relatives as well as an early detailed written epicrisis play a major role. This may be the only way to early counteract medically inane causal relationship being presented by the relative's advocate. Especially in the patient at high risk central venous catheterisation requires strict checking the indication, the corresponding choice of the correct technique during venipuncture, and a sufficient haemostatic pretreatment and care after catheterisation. PMID- 1892978 TI - Cell adhesion and growth on polymer surfaces with hydroxyl groups prepared by water vapour plasma treatment. AB - Various polymer surfaces--polyethylene, polypropylene, polystyrene, polyethylene terephthalate and poly(methyl methacrylate)--were modified by water vapour plasma discharge treatment. The plasma-treated polymer surfaces were characterized by water contact angle measurement and electron spectroscopy for chemical analysis. It was observed that by the water vapour plasma treatment, the wettability of the polymer surfaces increases largely and almost all functional groups produced on the surfaces are hydroxyl groups. The interactions of Chinese hamster ovary cells with the polymer surfaces having hydroxyl groups by plasma treatment were investigated. The cells adhered and grown on the polymer surfaces were counted using a haemocytometer and photographed with an inverted microscope with a camera attached. The water vapour plasma-treated polymers showed good adhesion, spreading and growth properties on the surfaces with high hydroxyl group density. We confirmed that the water vapour plasma treatment is a simple and effective method to produce hydroxyl groups on the polymer surfaces, which probably have a positive effect on cell adherence. PMID- 1892979 TI - Enhancement of cell growth on growth factor-immobilized polymer film. AB - Insulin, transferrin and collagen were immobilized on the surface of hydrolysed poly(methyl methacrylate) films. Mouse STO fibroblasts were cultured on the protein-immobilized films. Growth factors remained immobilized without detachment and accelerated cell growth in a more potent manner than free or adsorbed growth factors. Immobilized collagen enhanced the flattening of adhered cells in the early stages of cell adhesion, but did not enhance cell growth significantly. PMID- 1892980 TI - Structural alterations of p(HEMA)--collagen implants. AB - Samples of linear (additionally crosslinked) p(HEMA) with different amounts of fibrillar collagen were implanted into the popliteal region of rats. After 3 month, the implanted materials were harvested and examined by SEM. The implants underwent marked structural or morphological changes. While the fibrillar collagen was readily resorbed by invading cells, the synthetic constituent persisted to biodegradation. The p(HEMA) residues were shaped into spherical particles, approx. 1-15 microns in diameter. The possible fate of these microparticles in the host organism is discussed. PMID- 1892981 TI - Compositional variations in the surface and interface of calcium phosphate ceramic coatings on Ti and Ti-6Al-4V due to sintering and immersion. AB - The compositions of the surface and the interface of calcium phosphate ceramic (CPC) coatings electrophoretically deposited and sintered on titanium or its alloy, were determined by scanning Auger electron spectroscopy before and after 4 wk of immersion in a simulated physiological solution. In the CPC coating-metal interfaces, the phosphorus diffused beyond the titanium oxide layer. The phosphorus concentration in the interface followed a Gaussian distribution for both unalloyed and alloyed titanium. The diffusion depleted P in the ceramic adjacent to the metal. The surface of the ceramic, however, was substantially unchanged. A major change in the compositional depth profiles was induced by immersion: thick and uniform titanium phosphide layers of constant composition were observed on the Ti-based metal substrates. PMID- 1892982 TI - Effect of surface treatment on the dissolution of titanium-based implant materials. AB - Titanium and its alloys are widely used in load-bearing implants as a result of their excellent mechanical properties and corrosion resistance, but there is concern over the release of metal ions from the prosthesis. Our research investigated the influence of the surface oxide on the dissolution of the substrate material in saline solution, using a combination of atomic absorption spectroscopy, ellipsometry and transmission electron microscopy techniques. It is demonstrated that a substantial reduction in the release of metal ions may be achieved by ageing the surface oxide in boiling distilled water or by thermal oxidation; this is discussed in terms of the structure of the oxide film. PMID- 1892984 TI - Radiation grafting of hydrophilic monomers on to plasticized poly(vinyl chloride) sheets. II. Migration behaviour of the plasticizer from N-vinyl pyrrolidone grafted sheets. AB - The grafting of N-vinyl pyrrolidone, a hydrophilic monomer, on to flexible poly(vinyl chloride) sheets used in medical applications using ionizing radiation from a 60Co source was studied. The graft yield was found to increase linearly with monomer concentration and also with increasing radiation doses. The migration of the plasticizer di-(2-ethylhexyl)phthalate into a strong organic extractant such as n-hexane was studied at different time intervals for different grafted systems of poly(vinyl chloride) at 30 degrees C. The results indicated a drastic reduction in the leaching of the plasticizer from grafted systems versus ungrafted controls. Incorporation of ethylene dimethacrylate cross-linker during grafting did not seem to affect the graft yield considerably but appeared to further reduce the plasticizer migration. Surface energy calculations of the grafted samples indicate that the surfaces are highly hydrophilic compared to ungrafted poly(vinyl chloride) and the polar and dispersion components tend to vary with increasing cross-linker concentration. PMID- 1892983 TI - Microcapsules through polymer complexation. II. By complex coacervation of polymers containing a low charge density. AB - Relationships between ionizable group content, structure and molecular weight, solubility and solution behaviour, and the efficacy of ionic complex formation through complex coacervation, have been established for a range of sparingly soluble synthetic weak polyelectrolyte polymers with low charge content, based on hydroxyalkyl methacrylates. Selected polymers containing methacrylic acid (acidic) and dimethylaminoethyl methacrylate (basic) functionality show promise as capsule-forming pairs for the entrapment of mammalian cells. The solubility of basic polymers and their ability to form microcapsules with structural integrity is enhanced through quaternization of the N-methyl functionality to the quaternary ammonium group. The survival of guinea-pig erythrocytes encapsulated for 4 d in this promising system was shown by the Drabkin's test to be about 41% of the control sample. PMID- 1892985 TI - Microencapsulation of isolated pituitary cells by polyacrylamide microlatex coagulation on agarose beads. AB - Microlatex beads of homogenous size were made by polymerization of a mixture of acrylamide/bisacrylamide dispersed in a microemulsion. The microlatex was aggregated by dilution of the microemulsion in acrylamide solutions. The aggregates were then coagulated by polymerization at the interfaces of agarose beads circulating in a capillary tube containing paraffin oil. Biocompatibility was tested on isolated pituitary cells microencapsulated by this procedure. PMID- 1892986 TI - Short-term behaviour of two similar active glasses used as granules in the repair of bone defects. AB - The bioactivity of two similar vitreous materials used in the form of granules of 'critical' size was investigated in bone defects in jaws of two sheep. The granules consisted of Hench's Bioglass and another glass with the same chemical composition made in Italy. Two months after implantation, the sheep were killed and elemental analyses carried out on sections of the embedded jaws. The microanalyses for both the glasses showed a diffusion from the granules towards the surrounding tissue of silicon and sodium, and an inverse diffusion (from the surrounding tissue towards the granules) of calcium and phosphorus. The degradation for the Italian glass was slower than for the Bioglass. No significant osteoinduction was seen after that time at the interface of the glass granules or in the bone pocket. PMID- 1892987 TI - Calcium phosphate cements: effect of fluorides on the setting and hardening of beta-tricalcium phosphate-dicalcium phosphate-calcite cements. AB - Increasing amounts of fluoride ions have been found to increase the setting and hardening rates of beta-tricalcium phosphate-dicalcium phosphate dihydrate calcite cements. Thus, fluoride-containing cements reached a diametral strength of about 1.5 MPa after 15 d, but the fluoride-free reference sample reached only 0.45 MPa. The acceleration of setting and hardening is correlated to an increased rate of hydroxyapatite formation in the cement at the expense of dicalcium phosphate dihydrate and calcite. Adding monocalcium phosphate monohydrate and fluoride to the blends resulted in a marked decrease of their setting time from about 1 h down to 8 min, without greatly affecting their final strength. PMID- 1892988 TI - Thermally stimulated polarization studies of kidney stones. II. Effect of annealing and thickness. AB - To investigate the cause of the d.c. charged conductivity state of kidney stones, the effect of annealing and sample thickness on thermally stimulated polarization was studied. It was observed that the peak current decreased and the peak temperature rose with increasing annealing temperature and the sample thickness. The sharpness of the single peak decreased and the activation energy increased with both parameters. The results have been explained on the basis of the loss of water attached to calcium oxalate and calcium phosphate, denaturation of collagen and the ionic nature of the main constituents of the kidney stone. PMID- 1892989 TI - Plasma-induced surface modifications on silicone intraocular lenses: chemical analysis and in vitro characterization. AB - In contrast to the high standard of intraocular lens implantation today, lens fixation and the occurrence of secondary opacifications are still not satisfactory. We are working on an implant that builds a stable connection to the surrounding lens-capsule. Disc-shaped lenses made of poly(dimethylsiloxane) were treated with different kinds of plasma to bring functional groups to the surface. This allows further macromolecular coating. The results of the surface modifications were characterized by electron spectroscopy for chemical analysis, scanning electron microscopy, Fourier transform infrared spectroscopy and cell culture experiments. O2 plasma induces a rapid increase of functional groups on the lens surface. CO2 plasma has to be used for longer treatment periods to achieve the same increase, but as SEM shows, did not lead to surface damage up to periods of 300 s. Using O2 plasma for longer than 60 s, a crack formation occurred. Therefore, CO2 plasma may be a more effective and sensitive tool in grafting functional groups to the surface. PMID- 1892990 TI - Tantalum-loaded polyurethane microspheres for particulate embolization: preparation and properties. AB - Polyurethane microspheres having diameters in the range 150-1500 microns were prepared by condensation polymerization of toluene diisocyanate (TDI) with poly(tetramethylene glycol) (PTMG) of average mol wt 990 in an aqueous dispersion medium containing dioctyl sulphosuccinate (DOS) as the suspension stabilizer and 1,4-diazabicyclo[2.2.2]octane (DABCO) as the catalyst for polymerization. Incorporation of tantalum powder in the polymerizing phase led to the formation of Ta-loaded microspheres with good radiopacity. Microspheres were surface modified by grafting methacrylic acid (MA) on to them using gamma-radiation from a Co60 source. Conversion of the grafted MA into its sodium salt imparted hydrophilicity and slipperiness to the microspheres enabling them to pass through Teflon catheters without obstructing the catheter lumen. These microspheres may find application as radiopaque embolization agents. PMID- 1892991 TI - Mechanistic aspects of the interactions between fluoride and dental enamel. AB - For many years after the discovery of its caries preventive effect, fluoride was thought to be primarily active by lowering the solubility of the apatitic mineral phase of the dental hard tissues. Recent findings have shed new light on the mechanisms by which fluoride inhibits or delays dental caries. Fluoride present in the oral fluids alters the rate of the naturally occurring dissolution and reprecipitation processes at the tooth-oral fluid interface. Demineralization of enamel is inhibited by concentrations of fluoride in the sub-ppm range. Likewise, remineralization of incipient caries lesions (the earliest stage of enamel caries) is accelerated by trace amounts of fluoride. As these two processes comprise dental caries the physiological balance between hard tissue breakdown and repair is favorably shifted by fluoride. The driving force for both phenomena is thermodynamic, that is, fluorapatite or a fluoridated hydroxyapatite may form when fluoride is supplied at low concentrations. This article critically reviews the current information about tooth-fluoride interactions, both from laboratory and clinical studies. PMID- 1892992 TI - The interaction of salivary secretions with the human complement system--a model for the study of host defense systems on inflamed mucosal surfaces. AB - When complement first contacts salivary secretions, as when gingival crevicular fluid first meets saliva at the gingival margin, complement function is enhanced. The immediate potentiation of the complement system at equal volume ratios of serum to saliva is due to several factors, including the lower ionic strength of saliva when compared with serum and the presence of certain salivary glyproteins such as the nonimmunoglobulin agglutinins that appear to simultaneously activate C1 and affect (sequester) certain complement control proteins, such as Factor H. This initial potentiation of the complement cascade by saliva may aid in defending the area immediately above the gingival crevice from oral microbiota that are being coated with a combination of serous exudate components and salivary components. As serum becomes much more diluted with saliva (i.e., crevicular fluid moves away from the supragingival area), the acidic proline-rich salivary proteins (APRP) begin to disrupt the unbound C1q-C1r2-C1s2 macromolecular complexes. Thus, the APRP along with other C1 fixing substances in saliva appear to restrict complement function, but only when the ratios of saliva to serum exceed 250:1. Since certain salivary glycoproteins bind to viruses, the potentiation of the complement system by saliva may also play a role in neutralizing certain viral infections on mucosal surfaces where tissue transudates containing complement begin to contact mucosal secretions such as saliva. Again, the ratio of serous fluid to mucosal secretion appears to be an important factor. This article also discusses some of our preliminary data and speculations concerning the binding of the self-associating high-molecular-weight nonimmunoglobulin salivary agglutinins (NIA) with the envelope of the human immunodeficiency virus (HIV) and the possible cooperative role of C1q and fibronectin in aiding neutralization of HIV infectivity. PMID- 1892993 TI - Osteoclast differentiation. AB - The osteoclast is the primary bone resorbing cell. It is a highly specialized multinucleated cell whose primary function is to help in the control of calcium homeostasis. The osteoclast has been very difficult to study because of its relative inaccessability, low numbers, and fragility when isolated from bone. Recently, techniques have been developed to study the cell biology of the osteoclast that have expanded our ability to understand the biological and functional properties of osteoclasts. In this article, studies on the origin of the osteoclast are reviewed and the differentiation markers that are used to detect cells in the osteoclast lineage are discussed. Factors that affect osteoclast differentiation are presented and model systems currently in use for studying osteoclast differentiation are evaluated for their relative strengths and weaknesses. In addition, osteoclast differentiation during tooth eruption and root resorption and the effects of bone matrix elements on osteoclast differentiation are reviewed. PMID- 1892995 TI - [Benefit of physical exercise in medicine]. PMID- 1892994 TI - [Myocardial and pericardial symptoms as a presentation of brucellosis]. PMID- 1892996 TI - [Selective deficiency of IgA]. PMID- 1892997 TI - [Antihypertensive treatment and insulin resistance]. PMID- 1892998 TI - [Comments on a series of 762 cases of colorectal carcinoma]. PMID- 1892999 TI - [Rhabdomyolysis associated with Salmonella enteritidis infection]. PMID- 1893000 TI - [Diagnosis of Behcet's disease: new criteria]. PMID- 1893002 TI - [Osteoporosis versus osteomalacia]. PMID- 1893001 TI - [Giant cell arteritis and neurogenic diabetes insipidus. A casual association?]. PMID- 1893003 TI - [Structural changes of the erythrocyte membrane in myelodysplastic syndromes]. AB - Myelodisplasic syndromes (MS) is a group of hematological alterations with well known clinical, diagnosis, prognosis and therapeutic features. The etiology is still, however, unclear. Following the hypothesis of the lesion of the pluripotential cell, we have studied the composition of red cell membrane in 5 patients afflicted with MS (1 with refractory anemia; 3 refractory anemia plus excessive blast count and 1 chronic myelomonocytic leukemia). The red cells of the patients afflicted with MS has morphological alterations at examination in fresh. The most frequently observed being acanthocytosis and macrocytosis. Structurally, they showed an increase in the cholesterol/phospolipids (C/P) quotient, which was responsible for the increase of the cell area and macrocytosis. Meanwhile, the high level of sphingomyelin (SP) and its depletion of phosphatidil-ethanol-amine (PEA), justify the double population of red cells; one of which being acantocytes and the other has and aquired mutation of the genetic code, which confirms the chromosomic alterations widely described. We feel that our findings confirmed the hypothesis of the effects of an oncogen on the genoma of the mother cell, which can be causal of some acute leukemias and other genetically confirmed alterations. PMID- 1893004 TI - [Membranous nephritis after renal transplantation]. AB - 8 cases of membranous glomerulonephritis (MG) after renal transplants (RT) are presented; one being a recurrence of the original disease and the other 7 due to a different cause of renal insufficiency. The total incidence of MG after transplantation was 1.63%; 1.39% being the incidence of MG of new cases. Only 1 patient showed decrease of renal function and in this case the MG was accompanied by chronic rejection lesions. There was no sign of neoplasias nor drugs producing MG. As far as chronic infections are concerned, only one patient showed B antigen and it was not observed during the immunofluorescent test in the biopsy. 6 patients had urological complications after the renal transplant (3 cases of urinary fistula; 2 cases of obstructive uropathy; 1 case of short ureter). 2 patients experienced the start of hemodialysis due to focal and segmentary glomerulosclerosis. The beginning of proteinuria commences between 2 and 23 months after the RT (median 13,0 +/- 7,5 moths); with a range of between 2.0 and 12.0 gr/day (median: 6.8 +/- 3,2 Z gr/day), this being nephrotic in 4 cases. Proteinuria improved 1 case, and persisted in the other patients at the same level registered previous to the diagnosis. MG is a non-frequent complication or RT and is usually benign. Patients with post-transplant urologic complications could be considered to have a higher risk of developing a MG "de novo". PMID- 1893005 TI - [Acetylation polymorphism in lung cancer]. AB - The acetylation phenotype was determined, by means of sulfamethazine measurement, in 87 patients (83 male) with confirmed bronchogenic carcinoma and in 93 healthy control patients (41 male) of equal ages. 48 patients and 54 controls were classified as being "slow acetylators" (Ch2 n.s.) When the persons were individually analysed by phenotype, it was confirmed that the patients showed a significantly lower rate of acetylated sulfamethazine than the control group (p less than 0.02), owing to the poor acetylation of patients with small-cell lung cancer. This difference should be confirmed by more detailed pharmacokinetic studies before regarding it as a possible interference of paraneoplasic type. The polymorphism acetylator cannot be considered a genetic marker related to the risk of having lung cancer. PMID- 1893006 TI - [The use of thymostimulin in lymphoma and myeloma patients]. AB - The benefit of the immunomodulation properties of thymic hormones in patients receiving chemotherapy for malignant diseases is yet to be defined. The efficacy of thymostimulin (TP-1) on hematological tolerance is evaluated, the performance level, the number and severity of the infections and skin reactions in two groups of homogeneous and randomized patients, diagnosed as having lymphoma and myeloma. Both patient groups (receiving or not receiving treatment) consisted of 20 persons. This observation was carried out in 96 courses of chemotherapy in each group; no significant differences having been noted in respect of the performance status at the beginning nor at the end of the study period between the 2 treatment groups. The hematological tolerance to chemotherapy, skin reactions and number and severity of infections registered were not significantly different between the 2 groups. In conclusion, we were unable to confirm an improvement in the clinical parameters of the myeloma and lymphoma patients receiving chemotherapy and thymostimulin during the period of observation. PMID- 1893007 TI - [Usefulness of captopril as monotherapy and combination therapy in the treatment of arterial hypertension]. AB - The efficacy and tolerance of captopril was prospectively studied as monotherapy for blood hypertension (BH), as well as combined modality with thiazides diuretic and nifedipine as a third drug. 95 cases of BH were followed up for a period of 6 months. 43.15% of the patients who received monotherapy with captopril were controlled (diastolic BP less than 95 mmHg). Those patients who had a diuretic added showed a response of 71.75% and those administered 3 drugs showed a response of 81.25%. The decrease of BH was significant in all groups (p less than 0.01). There was a significant correlation (p less than 0.01) between the response to monotherapy and severity of BH (mild BH 67.50% and severe BH 35.20%). 6.5% of patients abandoned the treatment because of secondary effects. No alterations were noted in the blood test. Monotherapy with captopril is effective in control of mild and moderate BH. In resistant patients, the addition of a diuretic and nifedipine retard as a third drug is useful and well-tolerated in any type of BH severity. PMID- 1893009 TI - [Meningeal carcinomatosis in giant cell lung cancer]. AB - A case of patient with symptoms of L3-L4 roots affliction and IV cranial nerve lesion, caused by meningeal carcinomatosis secondary to giant cell lung cancer, is presented. The clinical features, diagnosis methods, and therapeutic possibilities in this case are commented on. PMID- 1893008 TI - [Plasmodium falciparum resistant to sulfadoxine/pyrimethamine in Senegal]. AB - In 1983, the first African cases of malaria due to Plasmodium falciparum resistant to sulfadoxine/pyrimethamine, were described. Currently, this resistance is frequently found in Kenya and Tanzania. It has also been described in other African countries. A young Spanish woman contracted Plasmodium falciparum malaria in Senegal and was treated in our hospital with sulfadoxine/pyrimethamine. Fever and symptoms disappear within two days. The thick smears taken on the eighth and thirteenth days of treatment contained an abundance of gametocytes, but neither trophozoites nor schizonts. As the risk of transmission of malaria to the rest of the community was considered practically nil, no other treatment was administered. A month late, she was admitted to the hospital due to fever, shivering, fatigue, loss of appetite and hemolytic anaemia. The thick smear test again showed trophozoites of P. Falciparum. Thus, it proved to be a delayed grade I resistance to sulfadoxine/pyrimethamine, detected in far west Africa. An oral dose of mefloquine was administered as well as a red cell transfusion. Both fever and symptoms finally disappeared. PMID- 1893010 TI - [Muckle-Wells syndrome associated with idiopathic interstitial pneumopathy]. AB - Muckle-Wells syndrome is characterized by recurrent episodes of urticaria, fever, polyarthralgia, deafness and secondary amyloid (AA type), familial type with autosome dominant features; few cases have been described. A case of a patient with idiopathic interstitial pneumopathy, diagnosed 7 years before the onset of clinical amyloid, is presented. The patient had lymph glands enlargement and nephrotic syndrome and died 18 months later due to renal insufficiency. We have not found this association previously described in any medical literature. PMID- 1893011 TI - [Treatment of neoplastic hypercalcemia]. AB - Hypercalcemia (HC) is a frequent complication of tumoral disease which should always be treated, tumor therapy being the best treatment. Occasionally, it can prove to be a medical emergency and should be treated without delay, especially where high risk patients are concerned. Sometimes, the treatment is not successful due to the fact that the drugs used in acute crises, although effective, have high toxicity; meanwhile, the drugs used for chronic HC lack the desired level of effectiveness and, in addition, tolerance problems are also implicated. In this paper, we consider the therapeutic schedule, based on physiopathologic mechanisms; and, the various drugs presently being used are reviewed. The therapeutic attitude to be followed during HC is indicated. PMID- 1893012 TI - [Mediastinal adenopathy as the sole manifestation of adult tuberculosis]. PMID- 1893013 TI - [Serum laminin: a good marker of the clinical and histological severity of alcoholic hepatopathy]. PMID- 1893014 TI - [Hematopoietic growth factors (CSFs)]. PMID- 1893015 TI - [Importance of plasma fibronectin in vascular diseases of diabetic patients]. AB - Fibronectin (Fn) is a glycoprotein secreted principally by vascular endothelial cells and its main function is to maintain the adhesion between the various cells and the substrates. Owing to these two features, the glycoprotein participates in several pathologies affecting blood vessels, such as atherosclerosis and diabetes mellitus (DM). In this paper, we studied the quantitative differences of this protein in diabetic patients with associated macro and microangiopathy. PMID- 1893017 TI - [Ceruloplasmin levels in patients with chronic obstructive bronchopneumopathy]. AB - The seric levels of ceruloplasmin in a group of 20 patients suffering of chronic obstructive lung disease were studied. Levels in this group of patients (51.42 +/ 11.15 mg/dl) (p less than 0.005) were significantly higher than those of the control group (36.59 +/- 13.37 mg/dl). There was no correlation between ceruloplasmin levels and PaO2, PaCO2, SaO2, HCO3- measurements. Results show a possible oxidation reaction; owing to the fact that ceruloplasmin is a general oxidase which, combined with an antioxidant stimulus of patients with chronic respiratory insufficiency, can produce this reaction. PMID- 1893016 TI - [Spread pattern of HIV-2 in patients at risk. Evaluation of serologic markers]. AB - The aim of this paper is to ascertain the spread pattern of HIV-2 in patients at risk in an area of frequent contact with sub-Saharan Africa and evaluate the seric marker of HIV-2 infection. 606 serum samples from 524 patients were analysed. 445 patients were intravenous drug users (IDU), 17 used inhaled drugs, 26 had HIV-2 (+)partner, and others 36 high-risk practice. The ser were analysed for HIV-1 and HIV-2, using ELISA, Western blot (LAVBLOT 1, LAVBLOT 2) and specific synthetic peptides such as gp 41 and gp 36 (PEPTI-LAV 1-2). 245 out of 524 (47%) patients were HIV-1 (+). 65 out of 524 (12.4%) were Elavia-2 and HIV-1 (+). All samples tests using Western blot 1, confirmed the results of the ELISA (2 protein of the membrane). The Western blot of HIV-2 Elavia-2 (+) in 2/53 showed two proteins of the membrane and 26/53 one protein of the membrane and several of the core. The PEPTIL-LAV 1-2 was HIV-1 positive in 77/77 HIV-1 serum samples and in 10 HIV-2 positive, however, in all cases the HIV-2 reactivity was lower than HIV-1, allowing the orientation of the diagnosis towards the HIV-1 positive serum. In spite of the frequent contact with Africa, the spread of HIV-2 in the south of Spain is still quite insignificant. The Western blot of HIV-2 gives a high proportion of double reactivity, including those cases with restrictive criteria to be positive. PEPTI-LAV 1-2 has proved most useful in the diagnosis orientation in the cases of crossed reactivity between HIV-1 and HIV-2. PMID- 1893019 TI - [Immunosuppression therapy with cyclosporin in inflammatory bowel disease: preliminary experience]. AB - Three patients afflicted with inflammatory bowel disease (1 UC, 1 Crohn's disease, 1 non-filiated colitis), who did not respond to the aggressive treatment from Oxford (3) were treated with immunosuppression therapy with cyclosporin. The dosage was 5-7 mg/day, to obtain seric levels (RIA) between 100-125 ng/ml during 3 months. All patients showed complete remission which was maintained for 6 months after the halt in treatment in the cases of the UC and non-filiated colitis. Parameters of cholestasis appeared with a transient increase of transaminase levels in 1 patient. Another patient suffered a pericarditis sicca which may not necessarily be related to the treatment. PMID- 1893018 TI - [Efficacy evaluation of cloxacillin and cloxacillin-gentamicin in an experimental model of methicillin-sensitive Staphylococcus aureus]. AB - 23 rabbits with Staphylococcus aureus methicillin-sensitive, SAMS, experimentally induced endocarditis (EIE) were studied to compare the efficacy of cloxacillin vs the association cloxacillin-gentamicin. Twelve animals made the control group and 11 the treated ones, 5 with cloxacillin-gentamicin and 6 with cloxacillin. The animals were treated 3 days, then, mortality, blood cultures at 48 and 72 hours and the title of the unit-forming colonies per gram of vegetation (UFC/g) were evaluated. The control group had a mortality of 100% in the first 72 hours, its blood cultures were positive at 48 and 72 hours and the UFC/g was 10,48 o 0.20. There was statistical significance between the control group and both treatment, in mortality, blood culture's positivity and the UFC/g of vegetation. This results confirm the similar efficacy of cloxacillin either alone or in combination in the treatment of SAMSIE and the effectiveness of the experimental model to evaluate antimicrobial treatments. PMID- 1893020 TI - [Arthritis, endophthalmitis and endocarditis caused by Escherichia coli]. AB - A female diabetic patient of 66 years old with acute pyelonephritis, caused by escherichia coli, was further complicated by bacteremia and a rare septic metastasis such as arthritis of the knee and coxa-femoral, unilateral purulent endophthalmitis with a loss of sight and aortic endocarditis which required a surgical change of valves, the posterior evolution being favourable. PMID- 1893021 TI - [Multiple myeloma, atypical presentation]. AB - Multiple myeloma is the most frequent type of bone tumor. Usually, lytic images in bone can be seen, the spread and sclerotic radiological pattern is presented. PMID- 1893022 TI - [A case of DIDMOAD syndrome with urologic symptoms]. AB - A new case of DIDMOAD syndrome is reported on. A complete description is given and the sequential associations are detailed; highlighting the fact that the frequently associated urinary alterations should be considered as part of the same disease. PMID- 1893023 TI - [Recurrent benign intrahepatic cholestasis. A case report]. AB - A case of benign and recurrent intrahepatic cholestasis in a 46 year old female is presented. This patient, who correctly coincided with the diagnosis criteria, had 2 episodes of jaundice and pruritus over a period of 4 years. The diagnosis criteria, clinical features, blood tests, etiopathogenesis and treatment are reviewed. PMID- 1893024 TI - [Original physiopathological integration and new treatment possibilities and approaches in breast cancer]. AB - The aim of this paper is unify the physiopathological mechanisms of breast cancer proliferation and its hormonal relations. A further objective is to determine a comprehensive integration of the different hormonal therapies, considering new alternatives which are at present in developing stages. We conclude, defining and recommending further ways to focus upon and treat this disease. PMID- 1893025 TI - [The socialization of the student]. PMID- 1893026 TI - [Cylindrical cell papillary thyroid carcinoma. A case report]. PMID- 1893027 TI - [Ehlers-Danlos syndrome: a case report]. PMID- 1893028 TI - [Jaundice as a presentation of pneumonia caused by Legionella]. PMID- 1893029 TI - [A case of fatal Mediterranean boutonneuse fever. Necropsy study]. PMID- 1893030 TI - [Fibromuscular dysplasia of the renal artery as a cause of arterial hypertension, a case report]. PMID- 1893032 TI - [Sudden death caused by electric mechanism (unitary model)]. PMID- 1893031 TI - [Chronic eosinophilic pneumonia and bronchial asthma: 2 cases]. PMID- 1893033 TI - [A new demographic classification of the family for the use in primary health care]. AB - The approach to the health-disease problem in the family requires a knowledge of demographic features. We propose a demographic classification based on the nuclear family. In addition to the extensive and single-parent families, the lack of family and the familial equivalents we subdivide the nuclear family depending on whether it has close relatives or not, the number of children, the existence of extended family or not, with relatives or aggregates, and the binuclear families or those of divorced people. On this basis, we have evaluated the demographic distribution of 917 families from the basic health areas of Albaicin and Cartuja in Granada, the Valle de Jaen, and Telde in Las Palmas. We have found the predominance of the nuclear family (76.8%) over the extensive (5.2%), as well as the relevance of the single-parent (8.9%) and the lack of family (7.7%) types. Among nuclear families, those with relatives in near areas come first (62.2%), followed by the extended type (19.6%). There is a remarkably low rate of numerous families (9.3%), while binuclear families are exceptional. As familial demography is a factor to be considered in clinical practice owing to its influence in the familial function and resources, we propose the routine use of this classification in the family history. PMID- 1893034 TI - [Tuberculous infection in schoolchildren of Les Borges Blanques]. AB - The results of the study carried out with tuberculin skin test in primary school students from Les Borges Blanques are reported, so as to characterize the epidemiologic pattern of tuberculosis in this community. The overall prevalence of tuberculous infection was 3.6%. A 27.27% of the vaccinated and 2.32% of the nonvaccinated population, respectively, had a positive reaction. The prevalence of individuals vaccinated with BCG was 5.18%. The influence of vaccination on the PPD result was apparent. The incidence rates, excepting the 1981 cohort where it was 0, ranged from 0.61 (1976 cohort) and 1.01 (1978 cohort). The calculated RAI was 0.35%, with a yearly decline of infection of 29%. We emphasize the low yield of the investigation of contacts. Forty-three people living with 11 converters were investigated. No instance of active infection was found and only four of them were candidates to chemoprophylaxis. PMID- 1893035 TI - [Daily variations in health care in a health area of Cuba]. AB - The daily variations of several medical care activities in a health area of Cuba were evaluated during the first semester of 1990. To this end, chronological series of the different activities were set up, and seasonal indexes were calculated from them. The selected method was the mobile mean, using a multiplicative model as a basis. The occurrence of seasonal changes in the behaviour of evaluated activities was found to be higher in the visits of family physicians in their clinics and in the home visits than in on duty staff. Monday was identified as the least used day. The possible reasons for these results are relate with the schedules of medical tasks and also with population habits. These results may be useful to improve the quality of the health area services. PMID- 1893037 TI - [Depressive states]. PMID- 1893036 TI - [A retrospective study of 469 cases of acute appendicitis. Importance of primary care]. AB - In the present study 469 cases of acute appendicitis, who were referred from the community and operated in the Surgery Service from the Soria Hospital, were retrospectively evaluated. The results showed an incidence of appendectomies lower than in other series (79.76 cases/100,000/year), with a higher frequency in males and in the age group between 10-30 years. No significant relation was found between symptoms and the correct diagnosis of appendicitis; however, the time of evolution influenced the number of hospital days and the degree of inflammation in the appendix. We emphasize the relevance of early diagnosis and the referral of the patient from primary care to the hospital stay and cost. PMID- 1893038 TI - [The stomach and the duodenum]. PMID- 1893039 TI - [Community participation in primary health care: friend or foe?]. PMID- 1893040 TI - [Renal carcinoma. Apropos of a chance diagnosis]. PMID- 1893041 TI - [Tuberculosis in Madrid]. PMID- 1893042 TI - [Treatment schedules in urinary infection]. PMID- 1893043 TI - [Comparison of blood pressure values in the clinic and at home: implications for the therapeutic decision]. PMID- 1893044 TI - [Analysis of admission to a hospital emergency service by means of a P-10 form]. PMID- 1893045 TI - [Prevalence of tuberculous infection in a basic health area]. PMID- 1893046 TI - [Evaluation of autonomic neuropathy in a diabetes protocol]. PMID- 1893047 TI - [Inter-consultations and complementary tests in a health center]. PMID- 1893048 TI - [Alpha 1-antitrypsin deficiency in primary care]. PMID- 1893049 TI - [Brucellosis. A possible case of interhuman transmission]. PMID- 1893050 TI - [Pediatric postgraduate education in primary health care]. PMID- 1893051 TI - [Cuba, United Kingdom and Spain: models of alternative primary health care? A report of 3 study cases]. PMID- 1893052 TI - [School children poisoning by ornamental trees]. AB - Eleven cases of poisoning of children who had chewed threads from the barks of trees subsequently identified as Robinia pseudo-acacia were detected in Sanlucar La Mayor (Sevilla). A retrospective study was carried out of all children who had chewed barks of these trees on the days 28, 29 and 30 of January. The data were collected from the daily record of emergencies. From the twenty fulfilled epidemiological questionnaires it was found out that the predominant symptoms were abdominal pain, nausea, "biliary" vomits and some degree of weakness. This fact points to the need to identify and to control the risk factors in a given milieu so as to prevent these occurrences. PMID- 1893054 TI - [Priorities in prevention and health promotion in primary health care: views of the professionals]. AB - The aim of the study was to define the health problems, preventive and promotional activities, and self care measures which have a high priority for the primary care professionals in our area. A Delphi study with two rounds of questionnaires. A 69.6% of a panel of professionals selected because of their remarkable degree of participation in clinical, educational, organizational or managerial activities in PHC participated in the study. Chronic diseases and the mental health disorders of the anxiety/depression type were considered the most important health problems. The detection and control of hypertension, medical counseling against smoking, and the compliance with the vaccination schedules were the most supported preventive interventions. Finally, the consulted professionals felt that it is necessary to promote self care in chronic diseases and in some acute conditions such as upper respiratory infections. The primary health care professionals considered as interventions with a high priority for health promotion the counseling of life style and the traditional interventions such as the compliance with the vaccination schedules of the hypertension programs. It is necessary to adapt the training of professionals to the priorities in PHC problems and activities. PMID- 1893053 TI - [Evaluation of clinical data and a technique of rapid detection (TestPack Strep A) in the diagnosis of acute streptococcal pharyngo-tonsillitis]. AB - We have evaluated the validity of the clinical data, the clinical impression (CI) of the physician and a rapid antigenic technique (RAT) for the diagnosis of acute streptococcal pharyngitis and tonsillitis (SPT). We evaluated 126 patients aged 7 60 years (October 1988-March 1989). The incidence of SPT was 19%. SPTs had a significantly higher frequency of lack of cough and sudden onset as isolated findings, and of the associations fever greater than 38 degrees C + exudate + lack of cough, and sudden onset + fever greater than 38 degrees C + exudate + lack of cough. CI had a sensibility (S) of 56%, a specificity (Sp) of 72%, a positive predictive value (PPV) of 32%, a negative predictive value (NPV) of 88% and an overall valve (OV) of 69%. The RAT had a S of 79.2%, a Sp 93%, a PPV of 73%, a NPV of 95%, and an OV of 90.5%. Only some clinical data are useful to diagnose SPT. The CI of the physician has a low predictive value, whereas TestPack Strep A is useful and has a similar value as pharyngeal culture. PMID- 1893055 TI - Haemostatic changes in long-distance runners and their relevance to the prevention of ischaemic heart disease. AB - Haemostatic changes may explain the paradoxical observations that regular exercise helps to prevent ischaemic heart disease but the risk of myocardial infarction and sudden death is actually increased during exercise. This study measured relevant haemostatic variables in 100 athletes before and after races of 10-26.2 miles duration and compared resting levels in athletes with 25 non exercising controls. Prothrombin time, kaolin cephalin clotting time, fibrinogen, factor VII, factor VIII clotting (one and two stage), von Willebrand factor antigen, euglobulin clot lysis time, fibrin degradation products, full blood count, mean platelet volume, and platelet aggregation to collagen, adrenalin and adenosine diphosphate were measured. The immediate post-race results showed the familiar rise in platelet count and factor VIII clotting but there was no evidence of consumption or thrombin modification of factor VIII clotting. Platelet aggregation to adrenalin was reduced after the race and fibrinolysis was increased (P less than 0.05). The athletes at rest showed no significant differences from controls in their coagulation factor levels but showed increased fibrinolytic activity and reduced platelet aggregation to adrenalin (P less than 0.05). These results suggest a hypocoagulable rather than a hypercoagulable state during running and are consistent with the epidemiological evidence that such exercise is beneficial in the prevention of ischaemic heart disease. PMID- 1893056 TI - Histidine-rich glycoprotein in thrombolytic therapy: has it clinical relevance? AB - The plasma concentrations of histidine-rich glycoprotein and plasminogen were measured and those of free plasminogen calculated in 34 patients with acute myocardial infarction treated with thrombolytic drugs. We investigated whether the plasma levels of histidine-rich glycoprotein and free plasminogen were associated with clinical parameters such as the occurrence and time of successful reperfusion, the incidence of reocclusion and the presence and extent of the systemic lytic state. The mean (+/- SD) pretreatment concentration of histidine rich glycoprotein was 1.08 +/- 0.24 U/ml, which was almost identical with the normal reference values. After thrombolysis, the mean level decreased slightly. We found no support for a role of these proteins in achieving therapeutic success and only a faint suggestion that histidine-rich glycoprotein might contribute to reocclusion. Surprisingly, the non- or only limited occurrence of systemic lytic state appeared to be associated with a low level of histidine-rich glycoprotein, instead of the high level expected on theoretical grounds. It is therefore unlikely that histidine-rich glycoprotein is of clinical relevance for thrombolytic therapy of acute myocardial infarction. PMID- 1893057 TI - Hydration of fibrinogen, fibrin, and fibrin degradation product (FDP) as estimated by nuclear magnetic resonance (NMR) spectroscopy. AB - The relaxation times (T1 and T2) of water proton in nuclear magnetic resonance (NMR) were measured with solutions containing bovine fibrinogen (Fbg), fibrin degradation products (FDP) and with fibrin-gel (Gel), at varying protein concentrations (0.7-70 mg/ml). Both T1 and T2 declined exponentially with increasing protein concentration. At a protein concentration of 35 mg/ml, the T1 of Fbg, Gel and FDP were 2.32, 2.12 and 2.82 s and the T2 values were 0.35, 0.17 and 0.70, respectively. The relaxation times for the control samples (0.2 M borate buffer) were 3.41 (T1) and 2.28 (T2). When the relaxation rates (the inverse of T1 and T2), R1 and R2 were plotted against the protein concentration, there were positive linear correlations between them. Using the slopes of the plots, the hydration value of each protein was calculated. The hydration value (g of H2O/g of protein) was 0.24 for Fbg, 0.34 for Gel and 0.14 for FDP. PMID- 1893058 TI - Interference caused by acid extraction in the study of diacylglycerol in platelets. AB - A neutral mixture of chloroform and methanol was compared to an acidic mixture of these solvents for the extraction of diacylglycerol from platelets labelled with 3H-arachidonic acid. Using a neutral solvent we found that thrombin caused a rapid increase in the radioactivity of diacylglycerol. With an acidic solvent there was 10 times more background radioactive diacylglycerol, but no increase was detected after stimulation with thrombin. Acidic extraction, but not neutral extraction, caused a small percentage of phosphatidylinositol and phosphatidylcholine to hydrolyse and form diacylglycerol. The extent of hydrolysis accounted for the greater amount of radioactive diacylglycerol found after acidic extraction of radiolabelled platelets. In addition, when platelets were extracted by the acidic solvent a modified form of hydroxy-heptadecatrienoic acid appeared, and thin-layer chromatography in two dimensions was required to separate it from diacylglycerol. It is therefore important to use a neutral extraction method when studying diacylglycerol in platelets. PMID- 1893059 TI - No transplacental passage of standard heparin or an enzymatically depolymerized low molecular weight heparin. AB - In 21 women who had an abortion by hysterotomy between the 15th and 23rd week of pregnancy, the possibility that unfragmented heparin or low molecular weight heparin (LMWH) passed the placental barrier to the foetus was studied. Laboratory analyses included amidolytic assays of factor Xa inhibitory activity (XaI), antithrombin III (ATIII) and a direct measurement of heparin-like substances in plasma with a competitive binding assay. The ATIII concentration in foetal plasma was about 20% of that in normal human plasma and varied considerably between individuals (2-27%). The XaI activity did not differ between the two treated groups, but the mean XaI activity of the combined groups differed from zero (P less than 0.05). If the XaI activity was corrected for the ATIII concentration, the heparin activities no longer differed significantly from zero. As the concentration of heparin-like substances were above the detection limit (0.35 microgram/ml) in 6/16 analysable samples of foetal plasma, a further 15 women who had not received any heparin were included as controls. In 12/14 analysable foetal plasmas heparin-like substances in concentrations above 0.35 micrograms/ml could be detected. Determination of heparin activity in foetal plasma is thus difficult due to the influence of endogenous ATIII on heparin assays. In conclusion, this study did not demonstrate any evidence for the passage of heparin or LMWH across the placental barrier. No differences were detected whether unfragmented heparin or LMWH had been given to the mothers. Our results also indicate the presence of an endogenous glycosaminoglycan in foetal plasma. PMID- 1893060 TI - Development of a simple collagen based ELISA assay aids in the diagnosis of, and permits sensitive discrimination between type I and type II, von Willebrand's disease. AB - We have developed and evaluated an ELISA-based collagen binding assay (CBA) as an aid in the diagnosis and classification of von Willebrand's disease (vWD). The assay is simple to perform, and appears capable of differentiating Type II vWD from Type I vWD. Using plasma samples from both affected and non-affected patients, or from normal individuals, data obtained using the CBA were directly compared to data simultaneously derived from a standard von Willebrand factor antigen (protein; vWFAg) ELISA, and from a standard ristocetin cofactor (RCof) assay. Plasma derived from vWD patients (both Type I and Type II) showed overall reduced levels of vWF as detected by all three assays. Mean levels as a per cent of normal for vWFAg, CBA, RCof were 47.3, 60.7, 31.1 for Type I patients (n = 37), and 34.9, 1.6, 11.9 for Type II patients (n = 16) respectively. However despite the reduced vWF levels detected in Type I vWF binding values for both the CBA and vWFAg showed near comparability (i.e. vWFAg:CBA ratio generally less than or equal to 1.0). These ratio values were thus similar to those observed using plasma derived from either individual normal donors, or from non-vWD affected patients. On the other hand, plasma from Type II vWD affected patients showed markedly disparent values, with increased (greater than 8.0) vWFAg:CBA ratios coincident with virtually absent CBA binding in these patients. Thus, the CBA as reported here does appear to constitute a novel functional assay capable of detecting qualitative vWF differences in plasma of affected vWD patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1893061 TI - Force monitoring of clot retraction during DDAVP therapy for the qualitative platelet disorder of uraemia: report of a case. AB - The qualitative platelet disorder of uraemia results in decreased primary haemostatic capacity which can result in significant blood loss during invasive procedures. Treatments of the disorder tend to be empirical and include measures such as aggressive dialysis, conjugated oestrogens, and use of DDAVP. Improvement in platelet function is typically monitored by repeated bleeding times. The variability of the bleeding time is an all too recognized limitation of its usefulness. We report here the case of a 35-year old male with end stage renal disease who presented with intractable bleeding secondary to peptic ulcer disease and haemorrhagic gastritis. Platelet function tests including bleeding time, platelet aggregation studies, and clot retraction measurements were monitored before and after intravenous administration of DDAVP (0.3 microgram/kg). The bleeding time which had been 8 min before DDAVP did not change. Platelet aggregation studies revealed improved aggregation by both collagen and adenosine diphosphate. Clot retraction forces were dramatically enhanced after DDAVP. Pre DDAVP clots containing 72 x 10(9) platelets per 1 and 1 g fibrinogen per 1 produced 90 dynes/cm2 of force at 800 s post-thrombin addition. Identical clots formed with blood drawn 2 h post-DDAVP produced 750 dynes/cm2. The DDAVP dose was repeated after 8 h with obvious slowing of blood loss. The marked effect of DDAVP on clot retraction may allow monitoring of DDAVP therapy utilizing this technique. PMID- 1893062 TI - Isolation and autolysis of human meizothrombin in the presence of dansylarginine N-(3-ethyl-1,5-pentanediyl)amide. AB - Human meizothrombin, a transient intermediate in the activation of prothrombin to thrombin, was isolated in the presence of dansylarginine-N-(3-ethyl-1,5 pentanediyl)amide (DAPA), an active site inhibitor of thrombin. Meizothrombin autolysis to meizothrombin autolysis to meizothrombin des fragment 1 (cleavage at Arg273- Thr274) at different DAPA concentrations was monitoed by gel electrophoresis or by the changed fluorescence intensity of the DAPA-protein complex. Meizothrombin autolysis could be described by apparent pseudo-first order kinetics and was not eliminated even in the presence of a 100-fold molar excess of DAPA. By fitting the autolysis rates observed at different DAPA concentrations to a simple inhibition model, the rate of uninhibited autolysis at zero DAPA concentration, 22 h-1, and the dissociation constant of the DAPA/meizothrombin complex, 5.9 x 10(-8) M, were obtained. The uninhibited autolysis rate so obtained was consistent with an estimate (19 h-1) obtained from gel filtration chromatography experiments. A surprising finding was that the data could not be described adequately without inclusion of a DAPA-insensitive, or background, rate of autolysis. We conclude that the active site of human meizothrombin can never be completely blocked and autolysis can never be completely prevented even in the presence of saturating concentrations of the active site inhibitor DAPA. PMID- 1893063 TI - New approaches to antiplatelet therapy. AB - The importance of platelets in the pathophysiology of cardiovascular and cerebrovascular disorders has been demonstrated by numerous clinical and pathological studies. Conventional antiplatelet agents are effective in both the primary and secondary prevention of vascular disorders, but suffer for the combined shortcomings of lack of selectivity and relative potency. Many new antiplatelet agents have been developed to overcome these differences, including serotonin receptor antagonists, prostanoid derivatives and antagonists, fibrinogen receptor antagonists, and selective thrombin inhibitors. In this review we consider the mechanisms by which these novel antiplatelet agents impair platelet function and their potential clinical utility. PMID- 1893064 TI - von Willebrand factor and platelet interactions with the vessel wall. AB - von Willebrand factor (vWF) is a multimeric glycoprotein which has a dual role in haemostasis, functioning as carrier protein for Factor VIII and mediating platelet adhesion to exposed subendothelium (SE). vWF interacts with components of the SE such as collagen and heparin-like glycosaminoglycans as well as with two platelet membrane receptors: glycoprotein (GP) Ib and GPIIb/IIIa. These multiple binding functions explain its definition as an adhesive protein. vWF promotes platelet adhesion at the high shear rates which correspond to the rheologic conditions of the microcirculation or of narrowed arterial vessels. The role of the vWF-GPIb interaction in platelet adhesion is well known; that of the vWF-GPIIb/IIIa interaction has been more recently demonstrated through the use of monoclonal antibodies (MAbs) or synthetic peptides blocking vWF-binding to GPIIb/IIIa. In addition, perfusion studies in native, non-anticoagulated blood emphasize the concept that vWF is also essential for thrombus formation at high shear stress. Thus, vWF fragments, synthetic peptides or MAbs blocking the functional domains of vWF represent potential therapeutic strategies to prevent the development of thrombosis. PMID- 1893065 TI - Platelets, coagulation, and fibrinolysis in sickle cell disease: their possible role in vascular occlusion. AB - Recent evidence suggests that sickle cell disease (SCD) can be considered a hypercoagulable state, in which both platelet activation and thrombin generation are abnormally increased. Although thrombosis is now known to play an important role in at least one of the vasocclusive complications of SCD, namely stroke, the significance of hypercoagulability in the pathogenesis of vascular occlusion in SCD remains unclear. This review summarizes current evidence regarding platelet, coagulation, and fibrinolytic abnormalities in SCD and their possible role in vascular occlusion. Potential implications for therapy are also discussed. PMID- 1893066 TI - Platelet storage and transfusion. PMID- 1893067 TI - An overview of current quality control procedures in platelet storage lesion and transfusion. AB - In brief the major tasks in quality monitoring of platelet concentrates are: (i) To ensure that the process is able to meet the product specifications. (ii) To steer the apheresis session and production laboratory towards prevention-oriented decisions. (iii) To provide data on where problems are likely to occur, helping to identify cause-and-effect relationships. (iv) To communicate information in rapid, accurate and simple ways to help both in the concept of pre-release testing and preventative maintenance. These can only be achieved by exchange of ideas and collaborative work between producer and user but, for the purpose of pre-release testing, the dMPV provides unique criteria for control of platelet concentrates by both users and producer and is a method of choice. The three criteria of acceptability--platelet number, platelet function and leucocyte count -can be effectively measured by one test on paired samples with excellent accuracy using a cell counter, helping to standardize quality determination. In several blood transfusions services a trend in this direction is already on the way. PMID- 1893068 TI - Platelet-mediated alterations in cardiac cellular electrophysiology. AB - Recent clinical and experimental evidence indicates that platelet activation contributes to the arrhythmogenic effects of myocardial ischaemia, but little is known about the electrophysiological effects produced by controlled platelet activation under conditions of normal perfusion and how these might relate to effects during ischaemia. To investigate this, we studied changes in cardiac cellular electrophysiology and arrhythmogenesis during infusion of platelets [10(8)/ml] in isolated, perfused guinea-pig hearts during normal perfusion and global myocardial ischaemia. Hearts were studied in four groups: group A (n = 4) receiving frozen/thawed (activated) platelets; group B (n = 4) receiving normal platelets in the presence of 10(-9) M platelet activating factor (PAF); group C (n = 9) receiving buffer only during normal perfusion and myocardial ischaemia; group D (n = 9) receiving platelets during normal perfusion and myocardial ischaemia. Infusion of platelets (group D) had no effects during normal perfusion, but activated platelets (group A) decreased action potential duration (APD) from 165 +/- 1 ms to 138 +/- 5 ms (mean +/- SE) at 15 min of normal perfusion (P less than 0.02) and produced ventricular fibrillation (VF) in 3/4 at 21 +/- 1 min. Infusion of platelets in the presence of PAF (group B) produced similar reductions of APD during normal perfusion and VF in 2/4. During ischaemia, platelets (group D) increased the incidence of VF (100% vs 56% group C, P less than 0.05) and enhanced the ischaemia-induced reductions in APD (107 +/ 3 ms vs 121 +/- 5 ms (group C) P less than 0.05 at 15 min).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1893069 TI - Monitoring the release of glycocalicin in platelet concentrates by ELISA. AB - Platelet membrane glycoprotein Ib (GPIb) is one of many GPs on the platelet membrane which contribute to the functional and morphological properties of platelets. A principal function of GPIb is its attachment to von Willebrand Factor (vWF) on injured blood vessels which leads to the adhesion of platelets to these vessels. The binding site to vWF resides on glycocalicin (GC), which is a major segment of GPIb. Glycoprotein Ib is particularly susceptible to centrifugation and storage of platelets. The assessment of GPIb status on platelets, therefore, comprises one of many traditional methods for monitoring the quality of platelets during storage. We have recently developed a novel ELISA to monitor GC levels in the supernatant of platelet concentrates (PCs) during storage. Using this ELISA we observed a progressive rise of GC in PC supernatants during storage. A recent study of citrated PCs with or without EDTA produced similar results, and showed a substantial increase of GC levels in EDTA-treated PCs. The GC ELISA could therefore be used as a novel method to monitor PCs during storage under various conditions. PMID- 1893070 TI - Platelet transfusions irradiated with ultraviolet-B light may have a role in reducing recipient alloimmunization. AB - The recipients of multiple platelet transfusions frequently develop alloantibodies directed against the human leucocyte antigens (HLA) present on both leucocytes and platelets. Such alloimmunization (AI) may result in refractoriness to further platelet transfusions. Contaminating leucocytes bearing Class II HLA and present in platelet concentrates (PC) are responsible for the formation of HLA antibodies and their removal by filtration reduces the rate of recipient AI. Ultraviolet irradiation (UVR) of PC at an appropriate dose inactivates the contaminating mononuclear leucocytes so that responses in vitro to mitogens and alloantigens are abrogated. It seems likely that UV-irradiation of donor dendritic cells (DC) is important in preventing in vitro responses to alloantigens and in vivo allosensitization. At the same time, satisfactory platelet function and structure is retained when measured by in vitro tests. In vivo assessments of platelet recovery and survival in healthy subjects and the ability to correct the bleeding time in thrombocytopenic patients are comparable to non-irradiated PC. Prospective studies are now in progress to determine if UVR will reduce recipient AI to HLA in multiply-transfused patients with leukaemia and lymphoma. PMID- 1893071 TI - Clinical aspects of platelet transfusions. AB - Refractoriness is the most important complication of platelet transfusion therapy, occurring in about 50% of patients receiving repeated transfusions. The major causes are HLA alloimmunization and non-immune platelet consumption associated with clinical factors such as septicaemia. DIC and splenomegaly. Initial management of alloimmunized patients who are refractory to platelet transfusions from random donors is the use of HLA-matched platelet transfusions, which improve responses to transfusions in about 65% of patients. It may be difficult to provide effective platelet transfusion support for alloimmunized patients not responding to HLA-matched transfusions. There has been much interest in methods for the prevention of HLA alloimmunization. Primary HLA alloimmunization is dependent on the presence of HLA class II antigen-bearing cells in transfusions; pure platelet transfusions are non-immunogenic as platelets only express HLA class I antigens. The use of leucocyte-depleted blood components in multitransfused patients has resulted in a reduction in HLA alloimmunization and platelet refractioness. Improvements in the techniques for leucocyte-depletion of red cell and platelet concentrates and the possibility of inactivation of HLA class II antigen-bearing cells by UV irradiation makes prevention of alloimmunization an attainable goal. PMID- 1893072 TI - In vitro evaluation of drug-induced toxic effects on the immune system as assessed by proliferative assays and cytokine production. PMID- 1893074 TI - Acridine-linked oligonucleotide probes for the short dAT-rich motifs in the 3' untranslated region of cytokine genes. AB - We have investigated the use of oligonucleotide probes for identifying cDNA clones containing the short dAT-rich motifs found in the 3'-untranslated region of cytokine genes. To obtain sufficiently stable duplexes between the octameric probes used to identify genes containing the sequence dTATTTATT and its complement, it was necessary to couple an intercalating agent, an acridine derivative (acr), to the 5'-positions of the probes. The resulting octamers 5' acr-dAATAAATA and, particularly, 5'-acr-dTATTTATT were successfully used to distinguish the complementary sequences in cDNA from internal, single point mismatched sequences. Southern blot analyses of plasmids containing IL-1 beta and IL-8 gave positive results with the 3' degenerate probe, 5'-acr-dTATTTATTN, clearly showing that the very short probe approach can be used in this type of analysis. Subsequently, in slot blot analyses we found that, even without the degenerate nucleotide, N, plasmids bearing cytokine sequences with at least 7 contiguous matched nucleotides could be unambiguously identified with 5'-acr dTATTTATT. Unfortunately, because of the ubiquity of these dAT-rich sequences in bacterial DNA, it was not possible to use these probes for direct colony screening. In contrast to the results obtained with DNA, at the RNA level, with IL-1 beta mRNA bound to nitrocellulose, the hybrid formed with 5'-acr-dAATAAATA was very unstable, even in 1M LiCl solution at 2 degrees C; however, in the same salt solution the slightly longer acridine-coupled probes 5'-acr-dAATAAATAGGG and 5'-acr-dAAAGAACAA remained hybridized to their complementary sequences up to about 18 degrees C. PMID- 1893073 TI - Regulation of synovial cell proliferation and prostaglandin E2 production by combined action of cytokines. AB - To study the causes of synovitis in rheumatoid arthritis (RA), we have analyzed the effect of several cytokines known to be secreted in RA joints, on synovial cell proliferation and prostaglandin E2 (PGE2) production. Recombinant interleukin-1-beta (IL-1-beta) and tumor necrosis factor-alpha (TNF-alpha) stimulated moderately the DNA synthesis and markedly the production of PGE2. Interferon-gamma (IFN-gamma) was often mitogenic but never induced PGE2 secretion. The association of IL-1-beta and TNF-alpha showed an additive effect on both parameters, whereas addition of IFN-gamma to either monokine reduced the proliferation and increased PGE2 release. Incubation with a crude T cell supernatant or a mixture of cytokines including IL-1-beta, TNF-alpha and IFN gamma enhanced synovial cell growth and PGE2 production as compared to the effect elicited by each single cytokine. In contrast, interleukin-2 (IL-2) down regulated the synovial cell activation induced by the combined action of the three other cytokines. Taken together, our findings indicate that synovial cell proliferation is weakly stimulated, reaching a two-fold increase over background levels, whatever cytokines are used. Furthermore, proliferation can vary independently of PGE2 production. Nevertheless, the monokines IL-1-beta and TNF alpha both exert agonistic effects on synovial cell activation, thus contributing to cartilage damage in RA, whereas IFN-gamma, IL-6 or IL-2 may rather play a regulatory role. PMID- 1893075 TI - Special issue on immunopathology. PMID- 1893076 TI - Postinfectious chronic fatigue syndrome: case history of thirty-five patients in Germany. AB - Thirty-five patients with chronic fatigue syndrome according to the criteria of Holmes were followed for periods of up to eight years. The most frequent symptoms were severe fatigue, arthralgias and myalgias, recurrent oropharyngitis and various psychiatric disorders. More than half of the patients suffered from neuropathy, lymphadenopathy, gastrointestinal complaints and recurrent low-grade fever. Recurrent or persistent activity of human herpesvirus -6 infection was seen in 73% of the patients and of Epstein-Barr virus in 34.4%. In addition, various other infections were diagnosed at lower frequency. Initial routine immunologic screening revealed various types of deficiencies, these were yet inconsistent and variable when different patients were compared with each other. Tentative treatments included in immunoglobulins, nonspecific immunostimulation and virostatic drugs. No consistently positive results were obtained with any treatment schedule although immunoglobulins appeared the most efficient measure. In addition, psychologic care of the patients is indicated, since disturbances in the psycho-neuroimmunologic regulation may play a significant role in the pathogenesis of the disease. PMID- 1893077 TI - How does the subjective experience of stress relate to the breakdown of the human immune system. AB - Life and health in a modern industrial society requires a continuous adaptation of the body to a variety of extraneous influences. Adequate adaptation is brought about by a balanced interaction of the nervous system, the endocrine organs, and the immunocompetent tissues. Deviation of such balanced response leads to "stress" in the sense of Hans Selye and may cause pathological reactions, i.e. disease. The present article reviews the current knowledge of functions and disturbances in the field of psychoneuroimmunology and endocrinology. PMID- 1893078 TI - Keratinocyte lipid fluidity under the influence of cholesterols, hydrocortisones, "active lipid", tocopherol and retinoic acid--a fluorescence polarization study with regard to physiological and pathophysiological epidermopoiesis and its therapeutic accessibility. AB - Lipid fluidity of freshly isolated human (H) and guinea pig (GP) keratinocytes (K) was determined as the reciprocal of diphenylhexatriene (DPH) fluorescence polarization (P-value), the temperature being kept at 25 degrees C and cell density standardized to 550,000 per ml (level of statistical significance a less than 0.05). An experimental model involving short-term incubations (2.5 hours, 37 degrees C) of GPK in 1% ethanolic lipid solutions (15 mg lipid agent per ml ethanol) was set up to investigate accumulation a) of cholesterol due to terminal differentiation of keratinocytes and b) of cholesteryl sulfate due to the lack of steroid sulfatase activity in recessive X-linked ichthyosis (RXLI). In comparison to the control including 1% ethanol (P = 0.291 +/- 0.004), significant rigidifying effects were demonstrated for cholesteryl hemisuccinate (0.331 +/- 0.005) and cholesteryl sulfate (0.310 +/- 0.002). Correspondingly, a significant increase of the P-value was also induced by cholesteryl hemisuccinate in HK. Rigidification of GPK by a preincubation with cholesteryl sulfate (P = 0.306 +/- 0.002) could be antagonized by a subsequent short-term incubation with "active lipid (mixture 721)" (0.285 +/- 0.003, a less than 0.05) which may be relevant for future therapeutic strategies in RXLI. Other steran molecules such as hydrocortisone-21-hemisuccinate or hydrocortisone acetate did not affect lipid fluidity. With regard to the therapeutic potency of retinoids in epidermopoietic disorders, incubations of HK with all-trans-retinoic-acid were compared to those with also lipophilic vitamin E, i.e. d-alpha-tocopherol, for 2.5 hours at 37 degrees C using 1% DMSO as a solvent.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1893079 TI - Rearrangements of immunoglobulin- and BCR-genes in chronic myeloid leukemia. AB - Clonal rearrangements of immunoglobulin (Ig) and T cell receptor (TCR) genes have been demonstrated in malignant lymphoid tumors of B and T cell origin. In Philadelphia chromosome (Ph1) positive chronic myeloid leukemia (CML) the bcr and c-abl genes are reorganized and a new transcript, composed of both genes is expressed. Immunoglobulin gene rearrangements were also detected in lymphoid blast crisis but not in myeloid blast crisis of CML. We analyzed in Southern blot experiments whether Ig and TCR rearrangements could also occur in the chronic or accelerated phase of the disease. Our results indicate that immunoglobulin but not TCR delta or TCR gamma gene rearrangements also occurred in some patients with CML in chronic and accelerated phase but not in myeloid blast crisis, together with rearrangements of the bcr gene. PMID- 1893080 TI - Altered membrane fluidity occurs during metabolic impairment of cardiac myocytes. AB - The purpose of this study was to evaluate the effect of impaired high energy phosphate metabolism on the membrane fluidity of cardiac myocytes. Cultured neonatal rat cardiac myocytes were treated with the metabolic inhibitor, iodoacetic acid (IAA) (30 microM). Membrane lipid fluidity was assessed by the steady-state fluorescence polarization of 1,6-diphenyl 1-1,3,5-hexatriene (DPH). Metabolic inhibition with IAA resulted in a progressive decrease in fluorescence polarization and calculated microviscosity. Microviscosity was decreased by 11% after 60-90 minutes and by 21% after 120-210 minutes, respectively. These changes are consistent with a progressive increase in membrane fluidity. Pretreatment with the experimental phospholipase inhibitor, U26, 384 (5-10 microM) resulted in a slower onset and less change in membrane fluidity after treatment with IAA. Thus, a) metabolic inhibition in cardiac myocytes induces prominent alterations in membrane fluidity which probably contribute to the membrane dysfunction accompanying myocardial injury and b) phospholipid degradation may be a significant factor in the genesis of altered membrane fluidity. PMID- 1893081 TI - Age dependence and prognostic impact of neuron specific enolase (NSE) in children with neuroblastoma. AB - Serum neuron specific enolase (NSE) was determined in 159 patients with neuroblastoma at diagnosis and in 183 children of various age groups. We found an age dependence of reference intervals for NSE and defined the 95th percentiles as upper normal limits. The specificity was 91.3% and the sensitivity 73.0%. The incidence of abnormal NSE levels increased with stage. The NSE serum levels were not influenced by histologic differentiation. Neuron specific enolase proved to be a reliable tumor-marker for monitoring the disease. Moreover, abnormal NSE values at diagnosis were of prognostic significance for patients with localized neuroblastoma (stages I-III) and for children with metastatic disease (stage IV), but not for infants with stage IV S. In comparison to catecholamine metabolite determination neuron specific enolase appeared to be a slightly less specific, equally sensitive tumor marker but with prognostic information for children with neuroblastoma. PMID- 1893082 TI - Chronic granulocytic leukemia in blastic crisis. Prognostic factors. AB - Thirty-nine patients with chronic granulocytic leukemia (CGL) in blastic crisis (BC) were studied from 1981 to 1988 at the Hematology Service of the General Hospital of Mexico. The patients were from 18 to 80 years old. Twenty-one patients (54%) were in lymphatic BC and 18 patients (46%) corresponded to BC myeloid. All the patients were treated with different chemotherapy schedules. Only three patients in lymphoid BC and two in myeloid BC achieved complete remission. The longest remission time was 24 weeks and the longest survival 36 weeks. The clinical and laboratory features, such as age, anemia, bleeding, fever, bone pain, adenopathy, splenomegaly, hepatomegaly, extramedullary infiltration, leukocyte count, hemoglobin, platelets, blast cells, in peripheral blood and bone marrow, basophils, and morphology and cytochemistry stains characteristic in bone marrow, were compared between the two groups of patients. None of the clinical and laboratory findings studied were significantly different between the two types of BC, except the evolution time from the diagnosis to the BC, which was more than than two years for most of the patients in lymphoid BC. We also studied the prognosis factors related to survival time. There were no clinical or laboratory differences among the patients who survived more than or less than 14 weeks.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1893084 TI - Platelet activation. PMID- 1893083 TI - Non-Hodgkin's lymphoma (NHL) of the testicle. A clinicopathologic study of 19 patients. AB - To investigate the frequency, clinical and anatomopathologic characteristics of non-Hodgkin's Lymphoma (NHL) present in the testicle as primary or secondary disease, we reviewed the files of the Hematology and Pathology Services of the General Hospital of Mexico, from January 1975 to December 1988. We found 681 cases of NHL in the Hematology Service; of these, 388 (57%) were male and 8 (2%) of them presented testicle involvement. Two were considered as primary disease, 4 as systemic disease and 2 as secondary or late complications. The overall mean age was 49 years. According to the New Working Formulation (NWF), 7 cases corresponded to the intermediate grade of malignancy and one to a plasmacytoma. The mean survival time of the whole group was 3.9 months. In the Pathology Department, the files of 203 autopsies of patients with NHL were reviewed; 124 (61%) were male and 11 (8.9%) of them presented testicle infiltration. In two, the testicular involvement was known before death and in 9 it was found at autopsy. In one case the infiltration was located in the epididimus and in other in the spermatic cords. The mean age of these patients was 50.7 years. In 6 cases there was extranodal infiltration other than in the testicle: 1 in the nose, and 1 in the central nervous system. According to the NWF, 1 was classified as of low malignancy grade, 7 were of the intermediate malignancy, and 3 of high malignancy grade. PMID- 1893085 TI - The effect of the selective PAF antagonist WEB 2170 on PAF and antigen induced airway hyperresponsiveness and eosinophil infiltration. AB - Exposure of normal guinea pigs to an aerosol of PAF induced an increase in airway responsiveness to i.v. histamine, 24 h and 48 h post challenge compared to animals that received BSA alone. There was no significant alteration in airway responsiveness 1 h, 4 h or 72 h after PAF challenge. Exposure of actively sensitised guinea pigs to an aerosol of ovalbumin induced airway hyperresponsiveness to i.v. histamine, 24 h post challenge. PAF induced a selective increase in the percentage of eosinophils in bronchoalveolar lavage fluid 24 h after challenge, that persisted for at least 72 h post challenge. No significant increase in eosinophils was noted 1-4 h after PAF exposure. Antigen challenge of actively sensitised guinea pigs induced a significant increase in the percentage of eosinophils recovered in BAL fluid 24 h post challenge. Pretreatment of both normal and sensitised guinea pigs with the selective PAF antagonist WEB 2170 significantly inhibited both airway hyperresponsiveness and airway eosinophilia 24 h post challenge with aerosol PAF or allergen. These results further support the suggestion that PAF may play a central role in allergen induced eosinophil infiltration and airway hyperresponsiveness in the guinea pig. PMID- 1893086 TI - WEB 2347: pharmacology of a new very potent and long acting hetrazepinoic PAF antagonist and its action in repeatedly sensitized guinea-pigs. AB - WEB 2347 is a new hetrazepine which is superior to the previously described paf antagonists WEB 2086 (apafant) and WEB 2170 (bepafant). This refers to both potency in vitro and in vivo (particularly after oral administration: e.g. the ED50 after oral administration is about 100 times less for WEB 2347 than for WEB 2086 to antagonize paf-induced hypotension in the rat) and duration of action (t1/2 = 41 h in the guinea pig and about 10 h in the rat after p.o. administration). Furthermore the role of paf in active anaphylaxis in vivo, even after repeated microshock, is strengthened. PMID- 1893087 TI - Renal allograft platelet activating factor synthesis during acute cellular rejection. AB - The aim of this study was to characterize the synthesis and metabolism of platelet activating factor (PAF, 1-0-alkyl-2-0 acetyl-sn3-phosphorylcholine) by renal tissue undergoing acute cellular allograft rejection in the canine model. Kidneys were transplanted into outbred mongrel dogs and allowed to reject without immunosuppressive therapy. Five days after transplantation, all kidneys were non functional and the tissue was assayed for the capacity to produce various molecular species of PAF and lyso-PAF using physical-chemical (GC/MS), immunologic (RIA) and biologic (platelet aggregation) assays. Renal cortical tissue obtained from rejecting allografts produced more PAF than control tissue by the following factors (GC/MS): 18-fold for C16:0 PAF; 3-fold for Lyso-C16:0 PAF; 2-fold for C18:1 PAF; and 6-fold for C18:0 PAF. The control tissue to which comparisons were made was renal cortex obtained from the native contralateral kidney. Increases in the production of various molecular species of PAF were also observed with renal medullary tissue undergoing acute rejection, although the magnitude of change was less dramatic than with renal cortex. The predominant PAF metabolite produced both by normal and allograft tissue was C16:0 Lyso-PAF. The increased PAF production by renal allograft tissue undergoing rejection was mainly attributable to C16:0 PAF and C16:0 Lyso-PAF, but increased production of both C18:0-PAF and of C18: 1-PAF was also detected. Increased renal allograft PAF production was also confirmed with a competitive binding immunoassay specific for PAF. In addition, when PAF-like material was isolated and purified from renal allograft incubation media and added to washed canine platelets, an intense aggregation response was observed that was abolished with prior alkaline methanolysis of the isolated material. Aggregation responses of similar magnitude were not obtained with PAF-like material isolated from native (non-rejection) renal tissue. In other experiment, incubation media obtained from rejecting renal allografts was found to contain factor which catalyzed hydrolysis of exogenous PAF to Lyso- PAF at twice the rate induced by media obtained from normal renal tissue. In conclusion, this study has identified dramatic increases in production of the biologically active molecular species of PAF by renal allograft tissue undergoing untreated cellular rejection. High levels of biologically inactive Lyso-PAF were also detected, and renal allograft tissue elaborates a factor which catalyzes rapid hydrolysis of PAF. PMID- 1893088 TI - The detection of multimeric forms of phospholipase A2 upon sodium dodecylsulfate polyacrylamide electrophoresis. AB - Monoclonal antibodies against rat liver mitochondrial phospholipase A2 were found to be cross-reactive with the phospholipase A2 present in caseinate-induced rat peritoneal exudate, both in dot-blot and in monoclonal antibody-Sepharose binding experiments. Immunoaffinity purification of the exudate enzyme yielded enzyme preparations with an estimated enrichment of about 54000-fold in a single chromatographic step. Sodium dodecylsulfate-polyacrylamide gelectrophoresis showed, apart from the presence of a 14 KDa phospholipase A2 band, several other bands at higher molecular weights. After Western blotting and immunostaining only a 14 kDa phospholipase A2 was detected, but upon storage of the sample in dodecylsulfate and dithiotreitol associated forms of this phospholipase A2 appeared. Similar tendencies to form multimers were observed starting from immunopurified and homogeneous phospholipase A2 preparations obtained from rat platelets and from rat liver mitochondria. This phenomenon is likely to be of general importance for the interpretation of results obtained in Western blots using antiphospholipase A2 antibodies. PMID- 1893089 TI - Gamma-aminobutyric acid induces feeding behaviour in the marine mollusc, Clione limacina. AB - The effects of gamma-aminobutyric acid (GABA) on the behaviour of the marine pteropod mollusc Clione limacina were studied. In intact molluscs, injection of GABA evoked the consummatory stage of feeding behaviour, i.e. protracting the tentacles, opening the mouth, catching and swallowing prey, as well as some acceleration of locomotion. In the isolated CNS, GABA (10(-5)-10(-4) M) strongly activated the feeding rhythm generator, excited the cerebral motoneurons innervating tentacle muscles (TenMNs), and accelerated locomotor rhythm. A direct excitatory action of GABA (10(-8) M) upon TenMNs was demonstrated on isolated cells extracted from cerebral ganglia. It is concluded that GABA plays an important role in activation of various neuronal networks (organization of 'functional synergy') responsible for the consummatory stage of feeding behaviour. PMID- 1893090 TI - Nucleus basalis lesions decrease alpha- and kappa-bungarotoxins binding in rat cortex. AB - A unilateral ibotenic acid lesion of the nucleus basalis magnocellularis in the rat, which is known to produce a reduction in cortical choline acetyltransferase activity and acetylcholine release, produces a decrease of 125I-alpha bungarotoxin and 125I-kappa-bungarotoxin binding sites in the frontoparietal cortex of the lesioned hemisphere. This decrease can be observed at two weeks following the lesion and persists for up to twelve weeks. The results suggest that a population of bungarotoxin binding sites may have a presynaptic localization. PMID- 1893091 TI - Photoablating neuronal groups using an intracellularly aggregating dye. AB - We report here on a new method to kill several selected neurons, using a modified fluorescence photoablation technique that does not require impaling any cells. Rather, we injected extracellularly the dye rhodamine 6-G, which is taken up by the cells. We made our injections into one side of a cockroach ganglion, after which the nearby cell bodies of individually known giant interneurons (GIs), as well as other cell bodies and many axons, became highly fluorescent. After this dye accumulation, we irradiated either the entire ganglionic region of the accumulated dye, or specifically the cell bodies of two identified GIs. After allowing over one week for axonal degeneration, both histological and behavioral tests confirmed that specifically the axons of the targeted illuminated cells had been killed. PMID- 1893092 TI - Brain potential signs of feature processing during auditory selective attention. AB - We recorded event-related brain potentials (ERPs) to random dichotic tone sequences as subjects attended to tone bursts of a designated pitch (250, 1000 or 4000 Hz) and ear of delivery. The effects of attention were isolated as negative difference (Nd) waves by subtracting ERPs to ignored tones from ERPs to the same tones when either one or both features were attended. Early sensory components of the ERP changed tonotopically in scalp distribution, while the distributions of Nd waves were feature-specific (pitch processing differed from location processing) but not tonotopic. At longer latencies, Nd waves specific to feature conjunction operations were isolated. These began 40-50 ms after Nds to isolated cues and continued for hundreds of ms. PMID- 1893093 TI - Subdural application of hemoglobin to the cerebellum blocks vestibuloocular reflex adaptation. AB - Vestibuloocular reflex (VOR) was induced by horizontal sinusoidal whole-body rotation in darkness in rabbits and a monkey. One eye was observed through an infrared TV camera. The gain of VOR was adaptively changed when the animal was continuously rotated for 3 h with the observed eye exposed to the screen moving in phase or out of phase with the head. Injection of 0.1 ml saline solution containing 10 microM hemoglobin into the subdural space over the cerebellar flocculus ipsilateral to the observed eye abolished the VOR adaptation. Since hemoglobin absorbs nitric oxide, which mediates synaptic plasticity in the cerebellar cortex, these results support the view that synaptic plasticity of the flocculus plays a key role in the VOR adaptation. PMID- 1893094 TI - Morphological correlates of persistent potentiation in the chick brain slice. AB - In an in-vitro slice preparation of the chick brain it is possible to induce persistent potentiation of responses to single electrical stimuli by giving two bursts of 300 stimuli at 5 Hz separated by ten minutes of control stimulation at 0.1 Hz. We investigated the morphological correlates of this potentiation in a group of 2 day old chicks using quantitative electron microscopical techniques. It was found that in slices which showed a clearly potentiated response there was a significant increase in the size of the postsynaptic densities of synapses on spines in the left hyperstriatum ventrale (IMHV). No such increases were seen in a control group nor in slices which failed to potentiate. These results provide further evidence for the lability of synapses in the IMHV. PMID- 1893095 TI - Spinal evoked potential P2 wave elicited by C fiber input and depressed by analgesic factors. AB - Spinal cord potentials were recorded from the surface of the spinal cord of rats. The effects of various treatments on a positive wave following the original P wave, which was evoked by strong electrical stimulation and named the P2 wave, were investigated. The results of this study demonstrate that capsaicin applied on to the sciatic nerve, intrathecal injection of morphine, electroacupuncture and noxious heat applied to the hindpaw contralateral to the recording side could suppress the P2 wave. These data suggest that P2 is mediated by C afferents and might be useful as a new indicator of spinal nociception. PMID- 1893096 TI - Cloning and characterization of a chalcone synthase gene from mustard and its light-dependent expression. AB - Genomic DNA from mustard was cloned in EMBL4 and screened for chalcone synthase (CHS) genes using a heterologous cDNA probe from parsley. Two clones which hybridized with the parsley cDNA probe were isolated. They showed different restriction patterns. One clone was sequenced and identified as a CHS gene by sequence comparison with published CHS sequences. The sequence of the coding region is 1188 bp, and encodes a protein of 43 kDa. The start-point of transcription was determined by primer extension. The sequence of 0.9 kbp at the 5' end of the transcription start and part of the noncoding 3' of this gene were also determined. The coding sequence is interrupted by a single intron of 523 bp. The coding and the noncoding 5' sequence of this gene was compared with CHS genes from other species. A very high homology was found with the Arabidopsis CHS coding region. A sequence motif (CACGTGT) which is present in most rbcS and all CHS upstream regions, and which specifically binds a protein factor from plant nuclear extracts, is also present in the upstream region of the mustard CHS gene. Measurements of CHS transcript levels show that phytochrome controls expression of this gene in cotyledons of mustard seedlings; however, blue/UV-light photoreceptors control expression in later stages of development. PMID- 1893097 TI - The combination of a novel stimulatory element in the first exon of the maize Shrunken-1 gene with the following intron 1 enhances reporter gene expression up to 1000-fold. AB - Both exon 1 and intron 1 of the maize Shrunken-1 (Sh1) gene individually stimulate expression of reporter genes in transient gene expression experiments if present within the transcription unit. The Sh1 exon 1 mediates a 10-fold increase in activity when inserted at the 5' end of the bacterial chloramphenicol transacetylase (CAT) marker gene in both monocot and dicot protoplasts. The Sh1 intron 1 enhances chimeric gene expression in rice and maize protoplasts approximately 100-fold but inhibits CAT expression in tobacco protoplasts. In combination, the stimulatory effects of Sh1 exon 1 and intron 1 are multiplicative in monocot protoplasts resulting in a final enhancement of up to 1000-fold compared to the unmodified CAT or luciferase marker genes. PMID- 1893098 TI - Evidence for an association of the early light-inducible protein (ELIP) of pea with photosystem II. AB - The precursor to the nuclear-coded 17 kDa early light-inducible protein (ELIP) of pea has been transported into isolated intact chloroplasts. The location of the mature protein in the thylakoid membranes was investigated after using cleavable crosslinkers such as DSP and SAND in conjunction with immunofractionation methods and by application of mild detergent fractionation. We show that ELIP is integrated into the membranes via the unstacked stroma thylakoids. After isolation of protein complexes by solubilization of membranes with Triton X-100 and sucrose density-gradient centrifugation the crosslinked ELIP comigrates with the PS II core complex. Using SAND we identified ELIP as a 41-51 kDa crosslinked product while with DSP four products of 80 kDa, 70 kDa, 50-42 kDa and 23-21 kDa were found. The immunoprecipitation data suggested that the D1-protein of the PS II complex is one of the ELIP partners in crosslinked products. PMID- 1893099 TI - Silencer region of a chalcone synthase promoter contains multiple binding sites for a factor, SBF-1, closely related to GT-1. AB - Bean nuclear extracts were used in gel retardation assays and DNase I footprinting experiments to identify a protein factor, designated SBF-1, that specifically interacts with regulatory sequences in the promoter of the bean defense gene CHS15, which encodes the flavonoid biosynthetic enzyme chalcone synthase. SBF-1 binds to three short sequences designated boxes 1, 2 and 3 in the region -326 to - 173. This cis-element, which is involved in organ-specific expression in plant development, functions as a transcriptional silencer in electroporated protoplasts derived from undifferentiated suspension-cultured soybean cells. The silencer element activates in trans a co-electroporated CHS15 chloramphenicol acetyl-transferase gene fusion, indicating that the factor acts as a repressor in these cells. SBF-1 binding in vitro is rapid, reversible and sensitive to prior heat or protease treatment. Competitive binding assays show that boxes 1, 2 and 3 interact cooperatively, but that each box can bind the factor independently, with box 3 showing the strongest binding and box 2 the weakest binding. GGTTAA(A/T)(A/T)(A/T), which forms a consensus sequence common to all three boxes, resembles the binding site for the GT-1 factor in light responsive elements of the pea rbcS-3A gene, which encodes the small subunit of ribulose bisphosphate carboxylase. Binding to the CHS15 -326 to -173 element, and to boxes 1, 2 or 3 individually, is competed by the GT-1 binding sequence of rbcS 3A, but not by a functionally inactive form, and likewise the CHS sequences can compete with authentic GT-1 sites from the rbcS-3A promoter for binding.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1893100 TI - New patterns of gene activity in plants detected using an Agrobacterium vector. AB - A vector has been designed that contains a truncated CaMV (cauliflower mosaic virus) 35S promoter fused to a receptor gene encoding beta-glucuronidase (GUS), placed adjacent to the left border sequence of an Agrobacterium vector. In potato plants transformed with this vector, different patterns of transcription were detected at high frequency using in situ assays for GUS activity. Previous studies in Drosophila using analogous vectors have shown that the new patterns of transcription in many cases reflect the patterns of expression of genes adjacent to the site of vector insertion. If this is also the case in plants, the vector described here will be useful in identifying the activity of genes in different cell types and will assist in determining their function. PMID- 1893101 TI - Isolation from wheat mitochondria of a membrane-associated high molecular weight complex involved in DNA synthesis. AB - A high molecular weight mitochondrial DNA (mtDNA) replication complex, associated with the mitochondrial membrane, was isolated by sucrose gradient centrifugation from purified wheat embryo mitochondria. This complex comprised the mtDNA as well as enzyme activities involved in the replication and transcription of the organelle genome, such as DNA polymerase, RNA polymerase and topoisomerase type I. The isolated complex is active in mtDNA and mtRNA synthesis in vitro. Electron microscopy and lipid analysis confirmed the membrane origin of this complex. Enzyme activities are resistant to physiological ionic strengths, 0.1-0.2 M KC1, while the membrane-mtDNA association is resistant up to 1 M KC1. DNase treatment of the complex released the DNA polymerase activity while protease treatment solubilized mtDNA, suggesting the direct interaction of mtDNA with membrane protein(s). The use of a novel approach to detect mtDNA fragments specifically retained by the mitochondrial membranes after Sal I digestion of the complex suggests that specific mtDNA sequences anchor mtDNA to mitochondrial membranes. PMID- 1893102 TI - cDNA cloning, characterization and expression of an endosperm-specific barley peroxidase. AB - A barley peroxidase (BP 1) of pI ca. 8.5 and Mr 37,000 has been purified from mature barley grains. Using antibodies towards peroxidase BP 1, a cDNA clone (pcR7) was isolated from a cDNA expression library. The nucleotide sequence of pcR7 gave a derived amino acid sequence identical to the 158 C-terminal amino acid residues of mature BP 1. The clone pcR7 encodes an additional C-terminal sequence of 22 residues, which apparently are removed during processing. BP 1 is less than 50% identical to other sequenced plant peroxidases. Analyses of RNA and protein from aleurone, endosperm and embryo tissue showed maximal expression 15 days after flowering, and high levels were found only in the endosperm. BP 1 was not expressed in the leaves. PMID- 1893103 TI - Cloning and sequencing of cDNAs encoding a pathogen-induced putative peroxidase of wheat (Triticum aestivum L.). AB - We report here the complete amino acid sequence of a pathogen-induced putative peroxidase from wheat (Triticum aestivum L.) as deduced from cDNA clones representing mRNA from leaves infected with the powdery mildew fungus Erysiphe graminis. The protein consists of 312 amino acids, of which the first 22 form a putative signal sequence, and has a calculated pI of 5.7. Sequence comparison revealed that the putative wheat peroxidase is most similar to the turnip (Brassica rapa) peroxidase, with which it shares 57% identical and 13% conserved amino acids. PMID- 1893104 TI - Nucleotide sequence of a cDNA clone encoding the wheat (Triticum durum Desf.) CM2 protein. PMID- 1893105 TI - Characterization of members of a pseudogene subfamily of the wheat alpha-gliadin storage protein genes. PMID- 1893107 TI - The sequence of a hydroxyproline-rich glycoprotein gene from Sorghum vulgare. PMID- 1893106 TI - Hemoglobin genes in non-legumes: cloning and characterization of a Casuarina glauca hemoglobin gene. PMID- 1893108 TI - Characterization of a cDNA clone encoding the Triticum aestivum L. CM16 protein: homology with the Triticum durum Desf. sequence. PMID- 1893109 TI - Differential accumulation of four phaseolin glycoforms in transgenic tobacco. AB - An intron-less phaseolin gene was used to express phaseolin polypeptides in transgenic tobacco plants. The corresponding amounts of phaseolin immunoreactive polypeptides and mRNA were similar to those found in plants transformed with a bean genomic DNA sequence that encodes an identical beta-phaseolin subunit. These results justified the use of the intron-less gene for engineering of the phaseolin protein by oligonucleotide-directed mutagenesis. Each and both of the two Asn residues that serve as glycan acceptors in wild-type phaseolin were modified to prevent N-linked glycosylation. Wild-type (beta wti-) and mutant phaseolin glycoforms (beta dgly1, beta dgly2 and beta dgly1,2) were localized to the protein body matrix by immunogold microscopy. Although quantitative slot-blot hybridization analysis showed similar levels of phaseolin mRNA in transgenic seed derived from all constructs, seed from the beta dgly1 and beta dgly2 mutations contained only 41% and 73% of that expressed from the wild-type control; even less (23%) was present in seed of plants transformed with the phaseolin beta dgly1,2 gene. Additionally, the profile of 25-29 kDa processed peptides was different for each of the glycoforms, indicating that processing of the full length phaseolin polypeptides was modified. Thus, although targeting of phaseolin to the protein body was not eliminated by removal of the glycan side-chains, decreased accumulation and stability of the full-length phaseolin protein in transgenic tobacco seed were evident. PMID- 1893110 TI - Multiple nuclear factors interact with upstream sequences of differentially regulated beta-conglycinin genes. AB - The expression of the alpha' and beta subunit genes of beta-conglycinin is differentially regulated during soybean embryo development. Although both are expressed solely in developing seeds during mid to late stages of embryo development, the alpha' subunit is expressed more highly on a per gene basis, and alpha' subunit mRNA begins to accumulate three to five days earlier than beta subunit mRNA. In cultured cotyledons, beta subunit gene(s) respond to changes in methionine or abscisic acid levels, whereas expression of the alpha' subunit gene(s) is unaffected by these changes. To investigate the mechanisms by which these genes are transcriptionally regulated, we examined the interactions of nuclear proteins with upstream sequences from the alpha' and beta subunit genes. Four distinct DNA binding factors were identified in nuclear extracts from developing soybean seeds. These factors are termed Soybean Embryo Factors (SEF) 1 through 4. SEF binding sites are distributed non-uniformly between the alpha' and beta subunit genes, and the amount of protein binding is modulated over the course of embryo development. DNA footprinting revealed the sequences recognized by three of these factors. Factors which behave in a manner similar to that of SEF3 were also identified in nuclear extracts from developing tobacco and sunflower seeds. PMID- 1893111 TI - Different promoter regions control level and tissue specificity of expression of Agrobacterium rhizogenes rolB gene in plants. AB - Expression of the rolB gene of A. rhizogenes T-DNA triggers root differentiation in transformed plant cells. In order to study the regulation of this morphogenetic gene, the GUS reporter gene was placed under the control of several deleted fragments of the rolB 5' non-coding region: carrot disc transformations and the analysis of transgenic tobacco plants containing these constructions identified the presence of distinct regulatory domains in the rolB promoter. Two regions (located from positions -623 to -471 and from -471 to -341, from the translation start codon) control the level but not the tissue specificity of rolB expression: progressive deletions of the rolB promoter starting from position 1185 to -341, although at different levels, maintained the same pattern of GUS expression-maximal in root meristems and less pronounced in the vascular tissue of aerial organs. Further deletion of 35 bp, from -341 to -306, drastically affected tissue specificity: GUS activity was still clearly detectable in the vascular tissue of the aerial organs while expression in the root meristem was totally suppressed. Analysis of transgenic embryos and seedlings confirmed that distinct promoter domains are responsible for meristematic (root) and differentiated (vascular) expression of rolB. Finally, we present data concerning the effects of plant hormones on the expression of rolB-GUS constructions. PMID- 1893113 TI - Sequences of two hsc 70 cDNAs from Lycopersicon esculentum. PMID- 1893112 TI - Analysis of two linked genes coding for the acyl carrier protein (ACP) from Arabidopsis thaliana (columbia). AB - Two linked genes, A1 and A2, coding for nearly identical isoforms of the acyl carrier protein (ACP) were isolated from an Arabidopsis thaliana (columbia) genomic library and sequenced. The amino acids deduced from the nucleotide sequence of the two genes indicate they encode distinct transit peptides, but the mature proteins are the same except for residue 79. Both genes are predicted to contain three introns in similar positions, although they differ in sequence and length. The introns interrupt regions coding for a) the transit peptide, b) the junction of the transit peptide and mature protein, and c) the highly conserved domain surrounding serine 38 to which the phosphopantetheine is attached. Primer extension analysis indicates that at least A1 is active in young plants. PMID- 1893114 TI - Nucleotide sequence of a rice genomic clone that encodes a class I endochitinase. PMID- 1893115 TI - DNA sequences of self-incompatibility genes from Brassica campestris and B. oleracea: polymorphism predating speciation. PMID- 1893116 TI - Microsporidia: opportunistic pathogens in patients with AIDS. PMID- 1893117 TI - Isospora belli infections. AB - I. belli is common in tropical and subtropical environments. Sporadic outbreaks have occurred in mental institutions and in day-care centers in the United States. The infection is common in immunosuppressed patients, particularly those with AIDS living in tropical areas. Transmission probably occurs by the fecal oral route. Chronic diarrhea is the major clinical manifestation. The pathophysiology of I. belli-induced diarrhea is unknown. Laboratory diagnosis is readily performed with the examination of unstained and stained stool specimens particularly by the modified Ziehl-Nielsen method. I. belli infection responds promptly to trimethoprim-sulfamethoxazole therapy and recurrent disease can be prevented with either trimethoprim-sulfamethoxazole or pyrimethamine-sulfadoxine. PMID- 1893118 TI - Schistosoma malayensis: the biologic, clinical, and pathologic features in man and experimental animals. PMID- 1893119 TI - Pneumocystis carinii pneumonia (PCP). PMID- 1893120 TI - Leishmaniasis and its etiologic agents in the New World: an overview. PMID- 1893121 TI - Heat shock proteins as vaccine candidates. AB - Parasite heat shock proteins are phylogenetically well-conserved antigenic mosaics that nonetheless stimulate both humoral and cellular immune responses during the course of infection. These range from highly specific to broadly cross reactive, with intermediate degrees also documented. The latter may prove beneficial, if they can be appropriately channelled to protect against multiple pathogens, or potentially harmful, if they cross-react with host components. Assessment of heat shock proteins as vaccine candidates has thus proceeded cautiously, with efforts being made to map the specificity of host immune responses to individual epitopes of the molecules. Ultimately, to serve as vaccines, the molecules must be recognized by the immune system within the context of a living pathogen, and be capable of inducing appropriate cellular and/or humoral immune responses that are effective at preventing establishment of individual pathogens. Reviewed are studies relevant to the use of parasite hsps as vaccine components, with emphasis on those from schistosomes, malaria, chlamydial, and mycobacterial parasites. PMID- 1893122 TI - Heat shock proteins: an autoprotective mechanism for inflammatory cells? AB - Heat shock/stress proteins are synthesized in all cell types under a variety of stressful conditions. Stress associated with ongoing inflammation relates, at least in part, to toxic products locally generated by cells accumulating in the inflamed tissue and organ. These products include oxygen free radicals, cytokines, proteases, chemotactic factors and, in the particular case of the eosinophil, toxic basic proteins. The heat shock response in inflammatory cells appears to be specifically regulated by their own proinflammatory products (oxygen free radicals, cytokines) generated during physiological functions such as phagocytosis, during differentiation, or in certain pathological states such as inflammatory lung diseases. We suggest that in human monocytes-macrophages heat shock proteins belong to the autoprotective equipment against oxidative stress. PMID- 1893123 TI - Tumor-specific immunogenicity of stress-induced proteins: convergence of two evolutionary pathways of antigen presentation? AB - Stress-induced proteins (hsps) elicit tumor-specific immunity to a number of murine tumors. Specificity of this immunity is puzzling in view of the fact that no tumor-specific DNA sequence polymorphisms have been identified in stress induced genes, nor is there evidence for tumor-specific posttranslational modification of hsps. In this light, the possibility that hsps may not be antigenic per se, but may be carriers of antigenic moieties such as peptides, and may be accessory antigen-presenting molecules, is considered. A model where an hsp molecule such as gp96 acts as an intermediate in presentation of peptides to MHC is discussed and it is suggested that the hsp and MHC antigens are mediators of independent but functionally convergent phylogenetic pathways. PMID- 1893124 TI - [Effects of gamma-aminobutyric acid antagonist, 4-ethyl bicyclo-phosphate, on total and synaptic evoked responses in neurons of hippocampal slices]. AB - Influence of 4-E-BPE on the amplitude of population spices (PS) evoked in CA1 area by Shaffer collateral stimulation in hippocampal slices were analysed. Bath application of 4-E-BPE (10(-6)-10(-5) M) led to a pronounced increase in the amplitude of the PS, the appearance of secondary PS and then introduction of GABA led to restoring original state. The 4-E-BPE was more potent than picrotoxin. These findings suggest that 4-E-BPE suppress inhibitory synaptic transmission in the CA1 region of hippocampus. PMID- 1893125 TI - [Effects of an inhibitor of gastric secretion from k-casein on micro lymphocirculation in the mesentery of the small intestine and intestinal motility in rats]. AB - The casein inhibitor of gastric secretion, when applied to the mesentery of anesthetized rat at doses 0.01-10.0 micrograms in 0.1 ml activated the lymph flow due to enhanced contraction of lymphatic microvascular wall and valves. Moreover, casein inhibitor administrated intraintestinally at doses 5 mg in 0.5 ml on rat keep its lymphotropic activity. PMID- 1893126 TI - [EEG--indicator of impairment and recovery of the dendrite structure in the plexiform layer of the cerebral cortex]. AB - The connection between EEG spectrum and structural changes of plexiform layer apical dendrites was revealed during the period of recovery from the deep anesthesia. On the initial phase of recovery when the multiply varicose dendritic enlargements are present, an additional peak in EEG spectrum emerged in a delta band under weak DC action (10 microA); on the late phase of recovery when the structure of the plexiform layer apical dendrites became normal the peak in EEG spectrum under weak DC action emerged in a tetha-band. Thus, by the absence or appearance of the tetha-rhythm in the cerebral cortex in the response to it direct stimulation we can evaluate the morphological condition of the Plexiform layer apical dendrites. PMID- 1893127 TI - [Sex differences in reserve capacity of the pituitary-adrenal system in rats]. AB - Female rats exposed to complex emotional stress for 1 hour (restriction in the penal, vibration, loud dissonance music, interrupt light) simultaneously showed more considerable increases in plasma and adrenal corticosterone values than did male animals. Female rat corticosterone levels returned to basal values within 20 120 minutes of stressor-off. As for males the processes of restoration were delayed and accompanied by a 6-fold decrease in the plasma corticosterone levels compared with basal values. The response to additional acute stress (immobilization for 10 minutes) in various times after termination of complex emotional stress (0, 40, 120, 180, 240 minutes) was facilitated in females and remained unchanged in males. Plasma corticosterone levels under stressful conditions were 2-4-fold higher in females than in males. It is concluded that reserve capacity of adaptation system is significantly higher in female rats than in male ones. PMID- 1893128 TI - [Activity of Zn-, Cu-containing superoxide dismutase in the brain tissue of rats with fetal alcohol syndrome]. AB - Zn(2+)-, Cu2+ superoxide dismutase activity was estimated in the brain of 14- and 30-day-old antenatally alcoholized rat offsprings. The enzyme activity in 14-day old experimental offsprings. The enzyme activity in 14-day-old experimental offsprings was significantly decreased in the brain cortex, hippocampus and brain stem by 27.1; 31.1 and 33.4% respectively as compared with control animals. The results are discussed from the point of view of the activation of free radical processes in the brain of alcoholized offsprings. PMID- 1893129 TI - [Experimental analysis of the formation of macro-reentry in the right atrium of rabbits]. AB - The aim of the present study was experimental demonstration of the formation of reentry in isolated preparations of the rabbit's right atrium, including sulcus terminalis, interatrial septum and AV node. Tachycardia was evoked by extrasystolic stimulation of the preparation. Reentry was identified by computerized multichannel mapping of excitation wave propagation. A series of sections performed in the area between the caval veins and the coronary sinus confirmed the presence of reentry pathway round the orifices of caval veins and through AV made zone. Local cooling and sections performed in different parts of the AV node showed that not all areas of AV node were involved in the formation of reentry, but only the perinodal (AN) area. These effects on the AN area terminated tachycardia. Linear dependence between the period of tachycardia and delay in the AV nodal zone was found. PMID- 1893130 TI - [Redistribution of myocardial blood flow in chronic ischemia under the effects of pharmacological agents]. AB - In the experiments with anesthetized dogs under chronic myocardial ischemia the effect of propranolol, diltiazem, lithium and sodium hydroxybutyrate on the myocardial blood flow redistribution was studied with the help of ultrasonic method. The redistribution was estimated by the ratio change of blood flows in veins which drain blood directly from the focus of myocardial ischemia and total myocardial of left ventricular (v cardiac magna). It was established that propranolol increases the ratio and diltiazem decreases it. Some differences in the effect of antihypoxic drugs were revealed. Sodium hydroxybutyrate redistributed the blood flow in favour of the focus of myocardial ischemia and lithium hydroxybutyrate increased the blood flow both in the focus of myocardial ischemia and in the conditionally-intact region of myocardium of left ventricular. PMID- 1893131 TI - [Experimental model of atherosclerosis induced by administration of acetylcholine into the reticular formation of the midbrain]. AB - Acetylcholine injections into the mesencephalon reticular system of rabbits every second day during a month induced atherosclerosis of the aorta. The microscopic examination of aortic intima showed lipomatosis, liposclerosis, atheromatosis, atherocalcinosis. PMID- 1893132 TI - [Mechanisms of hemolysis under the effects of extreme factors]. AB - It has been shown that the activation of reno-dependence mechanisms of destruction of the low-stable population of erythrocytes was observed following the acute blood loss, the infusion of the phenylhydrazine and uranyl-glycerine solution. These mechanisms have different nature: humoral (increase of hemolytic activity of the blood serum up to 46.6%), autoimmune-cell or vasorenal (increase of the autoplateformation in 1.8 ones, of the activity of the system mononuclear phagocytes on 37.6%). PMID- 1893133 TI - [Significance of estradiol in the development of fibrosis in systemic scleroderma (bases of sexual predisposition to the disease)]. AB - The influence of estradiol (E2) was studied on the production of type III procollagen by cultivated fibroblasts from the skin of healthy donors and SSD patients. It has been found that when in the norm E2 (concentration 10(-8) and 10(-7) M) inhibits the production of type III procollagen. In SSD the hormone's effect is not found. Here the quantity of E2 receptors in cells from SSD patients is 1.96 time lower than the norm. The resulted data testify to the fact that the decrease of E2 receptors in fibroblasts from SSD patients may be one of the factors contributing to the increase in the functional activity of cells and to the fibrosis progression. PMID- 1893134 TI - [Increase of accessibility of murine lens protein fluorophores to water in the development of radiation-induced cataract]. AB - The accessibility of tryptophanyl fluorophores in crystalline proteins to water molecules was estimated by measuring the enhancement of the fluorescence of lens homogenates in 70% D2O as compared to 100% H2O. Assuming that two sorts of fluorophores exist in the proteins, one entirely accessible to H2O and D2O and the other--absolutely not, we have calculated the portion of either group in the protein fluorescence (alpha and 1-alpha, correspondingly). Measurement of murine lens homogenates fluorescence at different stages of radiation-induced cataract, initiated with total gamma irradiation in a dose 5 Gy have shown an increased accessibility of tryptophanyl for water with cataract development. At earlier stages of cataract (appearance of scattered dot opacities) the portion of water accessible tryptophanyl increased from 0.14 to 0.18, i.e. by a factor of 1.3. The data obtained suggest that protein globules unfold in the coarse of cataract development. PMID- 1893135 TI - [Glutamate dehydrogenase activity in the pancreatic tissue in acute experimental pancreatitis and under the action of sodium thiosulphate]. AB - It has been established that the development of acute pancreatitis is accompanied by the reduced activity of glutamate dehydrogenase in the mitochondrial fraction of pancreas, pronounced in the focus of tissue necrosis and less expressed in the reactive inflammation focus. Besides this in the pancreas redistribution of enzyme, activity in the subcellular organelles takes place and enzyme activity emerges in the cytosol and further--in the blood and peritoneum liquid. Sodium thiosulfate has a marked correlation effect. PMID- 1893136 TI - [Detection in the structure of influenza viral proteins of sequences similar to vasoactive intestinal peptide]. AB - The paper presents the results on the influenza virus proteins (only HA, M and NS) contained in the amino acid sequence regions similar to that of the VIP. These data may be important as there is similarity in pathological reactions between VIP and influenza virus. PMID- 1893138 TI - [Ca2+-pump in myocytes of the small intestine]. AB - The characteristics of Ca(2+)-pump in smooth muscle of the rabbit small intestine were established. It was shown that Ca(2+)-pump was activated by the calmodulin and blocked by the oxytocin. PMID- 1893137 TI - [Study of functional properties of chemically-modified hemoglobin during circulation in the blood channel]. AB - Functional activity of the solutions of chemically modified hemoglobins (Hb) with different structure had been investigated during the replacement of acute fatal blood loss in dogs. It was found the correlation between polymerization degree of Hb derivatives and alterations of its oxygen-carrying characteristics in the process of circulation. It was shown that decline of functional activity at the prolonged terms of circulation was more expressed for macromolecular Hb derivatives with heterogeneous structure. Therefore chemically modified Hb free from high molecular weight fractions may be considered as a potential oxygen carrying fluids, because they are capable of more effective support of the oxygen transport level in the organism. PMID- 1893139 TI - [Indices of hexosamine-containing biopolymers in experimental tooth replantation]. AB - The experimental findings showed that the content of hexosamine-containing biopolymers, in periodontal tissue increased by 38.23 and 124% conformably over 14 days after replantation of 4 teeth of the dogs. The indices normalized in 28 days of the experiment. Investigated biochemical parameters in the root of replantation tooth, in osseus tissues of alveolus 2nd blood. Changed slightly in dynamics. PMID- 1893140 TI - [Sodium-calcium metabolism in myocytes of the small intestine]. AB - It is established that Na+/Ca2+ antiport of small intestine myocytes of plasmatic membranes has the saturation by the transfer substrate. It is characterized by the reversibility and dependence on the membrane potential. PMID- 1893141 TI - [Atherogenic effect of beta-blocker propranolol revealed in the rabbit denudated aorta]. AB - The influence of beta-blocker propranolol onto atherogenic properties of blood serum and to formation of myointimal thickening in rabbit aorta, which was caused by denudation, were investigated. The preparation was introduced per os in the dose 6 mg/kg. Culture of mouse peritoneal macrophages was used to estimate the atherogenic properties of the serum. Serum of propranolol-treated rabbits induced accumulation of cholesterol in cultivated cells. Propranolol also induced an increase of the thickness of aortic intima, lipid accumulation and increasing of cell's number in myointimal thickening. Thus, atherogenic effect of beta-blocker propranolol was found both in vitro and in vivo. PMID- 1893142 TI - [Increase of life span in mice under acute cooling and effects ofa preparation isolated from Laminaria saccharina]. AB - Efforts against cold is a significant problem during work in the Arctic. In experiments on grey mice it was demonstrated that drugs from Laminaria Saccarina increase life time of animals in cold temperature (-18 degrees C) by 61%. PMID- 1893143 TI - [Effects of ethomersol on cerebrovascular blood circulation and oxygen metabolism of the brain in acute transient ischemia and recirculation]. AB - Intravenous infusion of ethomersol (50 mg/kg during 60 min) decreased cerebral tissue hypoxia at the end of acute cerebral ischemia in cats (30-min occlusion of both carotid and both vertebral arteries). In recirculatory period ethomersol prevented the postischemic hypoperfusion and especially hypo-oxygenation. Ethomersol-induced reduction of Hb-affinity to O2 was demonstrated. PMID- 1893145 TI - [Characteristics of creatine kinase isoenzyme spectrum in the blood of rats in aging and acute alcoholic intoxication]. AB - The study of creatine kinase (CK) activity in biological liquids of rats of different age has shown that CK blood activity is decreased in aged rats. Acute alcohol intoxication leads to significant increase of CK blood activity. PMID- 1893144 TI - [Effects of allapinin on sodium currents in isolated neurons of the trigeminal ganglia and cardiomyocytes of rats]. AB - Block of sodium currents by allapinin (diterpene alkaloid with strong antiarrhythmic properties) was investigated in isolated, voltage clamped rat trigeminal neurons and cultured neonatal rat single ventricular myocytes. Allapinin produces a decrease in sodium current amplitude without any changes in voltage dependent properties. Possible differences between the mechanisms of antiarrhythmic effect of diterpene alkaloids and classic antiarrhythmic agents have been analysed. PMID- 1893146 TI - [Effects of phospholipid platelet activation factor on proliferation of B lymphocytes of the peripheral blood of healthy donors and patients with bronchial asthma]. AB - The influence of the phospholipid platelet activation factor (PAF) was studied on pokeweed mitogen (PWM)-stimulated proliferation of peripheral blood lymphocytes in patients with bronchial asthma and normal subjects. It was found that PAF exerts dose-dependent activation with following suppression mainly on B-cells after its action on the whole population of lymphocytes activated by PWM. Besides, the influence of PAF on lymphocyte proliferation seemed to be mediated by monocytes since removal of monocytes from the whole population of mononuclear cells abolished the lymphocyte activation induced by PWM. Indomethacin inhibits lymphocyte proliferation activation induced by PAF. The results indicate that PAF has an effect on the IgE and IgG synthesis by blood B-lymphocytes in patients with bronchial asthma. PMID- 1893147 TI - [Interactions of mononuclear cells of peripheral blood with islet cells in vitro]. AB - Peripheral blood mononuclear cells from Type I diabetic patients health donors or Wistar rats were cultured with rat islet cells for 18 h. Then TNF content of the medium and basal and stimulated insulin release were determined. Mononuclear cells from both healthy donors and diabetic patients could inhibit the insulin release with no correlation to TNF content. Addition of lipopolysaccharide resulted in a 5-7 times increase of TNF content of the medium followed by a more pronounced inhibition of insulin release. Rat mononuclear cells inhibited the beta-cell function almost completely and initially produced large amounts of TNF. The data indicate that inhibition of insulin release by blood mononuclear cells in vitro does not reflect anti beta-cell specific cellular immunity, involves cytokines and, probably depends upon the initial properties of the cells. PMID- 1893148 TI - [Distribution of ticks in the granary complex and their role in sensitization of Moscow inhabitants]. PMID- 1893149 TI - [Proliferative reaction of the epithelium of gastric glands to vagotomy and sympathectomy]. AB - By means of autoradiography and metaphase arrest technique 24-hour rhythms and intensity of proliferative processes in the epithelium of gastric glands were studied, as well as morphometric status of these structures after vagotomy and drug sympathectomy in the rat. In both cases the reaction of glandular epithelium appeared with the increase of mitotic activity and the decrease of cell synchronization before the entry into DNA--synthesis and mitosis. The number of epithelial cells in gastric glands became reduced, but after vagotomy, unlike sympathectomy, mainly because of the lack of chief cells. Thus, the trophic control upon the dynamic structure of gastric glands may have different mechanisms of realization for parasympathetic and sympathetic nervous system, probably, through the influence on cell proliferation or differentiation. PMID- 1893150 TI - [Effects of Eleutherococcus on the biorhythm of indices of peripheral blood in dogs]. AB - The circadian rhythms of the erythrocytes, hemoglobin and leucocytes concentration in the peripheral blood in dogs in winter and the effect of the eleutherococcus multi-injected at different periods of the day, were studied. The changes in the parameters of the studied biorhythms indices were observed only in the after dinner-injected animals, they being marked by the evident increase of the mesor and amplitude, acrophase shift by 1-2 hours by the beginning of the twenty-four hours. PMID- 1893151 TI - [Effects of endotoxin on oxidative metabolism of polymorphonuclear leukocytes]. AB - The influence of endotoxin on rat polymorphonuclear leucocytes (PMN) ability to generate oxygen free radicals (OFR) has been studied by chemiluminescence method. PMNs derived from intact animals were used as a control. PMNs derived from animals with 1.5 h endotoxemia increased OFR production after stimulation by latex. In contrast, PMNs derived from intact animals and preincubated with endotoxin for 1.5 h decreased OFR production after stimulation bw latex. It was proposed that stimulating effect of endotoxin on PMNs in vivo was mediated by plasma components. PMID- 1893152 TI - [Action of dithiothreitol on protein pattern and phosphorylation in nuclear matrix preparations isolated from the rat liver and Zajdela's hepatoma]. AB - After rat liver nuclei had been treated with 10 mM dithiothreitol nuclear matrix contained 40 per cent less protein than without treatment. Protein composition did not change qualitatively. The protein with a molecular weight of 35 kD was not phosphorylated in the treated samples. After Zajdela hepatoma nuclei had been treated in the same way, nuclear-matrix contained 25% less protein. High molecular weight proteins (140, 150 and 220 kD) were solubilized by media containing dithiothreitol. After dithiothreitol treatment phosphatase and protein phosphatase activities reduced dramatically both in rat liver and Zajdela hepatoma nuclear matrices. PMID- 1893153 TI - [Biological rhythms of tissue basophils of the dura mater of rats under the effects of noise-vibration]. AB - The biorhythmologic changes of tissue basophils (mast cells) have been investigated of mater rats in frontal, temporal and occipital regions of dura mater during the noise-vibration stress. Local differences were found in biorythmological characteristics of tissue basophils before and after vibration. The investigated regions of dura mater after noise-vibration stress the magnitude of harmonics, mesor and the amplitude of fluctuations increased greatly. But, judging by their values, in the temporal region the rhythm stability was lower than that in the frontal and occipital. The tissue basophils of various regions of dura mater react in a different way to the noise-vibration stress. PMID- 1893154 TI - [Morpho-functional analysis of median-sector approach in abdominal surgery]. AB - The article presents comparative analysis of original median-link access in abdominal surgery under various surgical interventions on the abdominal cavity organs. On the vast experimental material including 60 rabbits and data of clinical observation of 426 patients with different surgical diseases the authors showed the advantages of median-link access. PMID- 1893155 TI - [Accumulation of anomalous glycopolymers in the walls of main lymphatic vessels of the extremities in patients with chronic lymphedema]. AB - Redistribution of lectin receptor sites in the mam-lymphatics of human extremities in primary and secondary lymphedema in comparison with normal lymphatics has been investigated using conjugates to peroxidase of LCA, PNA, RCA, SBA, WGA and LAA. Chronic lymphedema caused no essential differences in lectin binding to tissue structures of intima and adventitia: endotheliocytes were strong reactive both with LCA, PNA, WGA and LAA; all lectins used bound fibrillary structures in subendothelial layer and adventitia. On the opposite, tunica media of main lymphatics in primary lymph stasis displayed accumulation of LCA-, PNA-, SBA- and LAA-binding deposits round smooth myocytes. When PNA used, the appearance of a specific "wide loop shaped reticulum" within lymphatics media in lymph stasis was observed. We consider, that lectin receptor sites accumulation phenomenon reflects some changes in smooth myocytes metabolism, possibly caused by dystrophia of these cell population with consequent incomplete glycosylation of synthesized glycopolymers. PMID- 1893156 TI - [Changes in ultrastructure and actomyosin complex of cardiomyocytes in experimental hypergravitation]. AB - There were studied the cardiomyocyte ultrastructure, contractile function, actomyosin complex composition and property of the rat ventricular myocardium after repeated gravitational overloading and following rest. In the hypergravitation period cardiomyocyte changes carry destructive character or are regenerative processes manifestation. They are comparable with myocardial contractile function state and with displacements in molecular structure of myofibrillar apparatus. At rest conditions the liquidation of cardiomyocytes destructive changes falls behind the normalization of contractile and regulatory cells of physico-chemical characteristics. The possible reasons of this phenomenon are discussed. PMID- 1893157 TI - [Morphofunctional characteristics of cadmium-induced arterial hypertension]. AB - Chronic (12 weeks) peroral administration of cadmium chloride to albino rats in a dose of 2.5 mg/100 g body weight results in arterial hypertension characterized by the increase in systolic blood pressure up to 148 +/- 1.8 mm Hg (vs. 115.4 +/- 1.5 mm Hg in the control animals); the increase in vascular resistance, left ventricular cardiomyocyte hypertrophy, as well as by hypertrophy of arterial walls, the decrease in the ventricular index, the activation of synthesizing function of atrial endocrine cardiomyocytes; enhanced secretion of ANP; a more than two-fold increase in plasma myoglobin concentration, as well as by the development of cadmium-induced nephropathy. In the rehabilitation period (9 weeks) a relatively quick fall in the blood pressure is observed, as well as morphological features of myocardial and renal function recovery, suggesting the nonpersistent nature of cadmium-induced hypertension. PMID- 1893158 TI - [Pathomorphological evaluation of combined antitumor therapy using cytostatics and immunomodulators in mouse lympholeukemia]. PMID- 1893159 TI - [Scanning electron microscopy of blood monocytes after long-term effects of ethanol]. AB - The surface architectonics of the blood monocytes from noninbred female rats after permanent oral administration of ethanol within 2, 5 and 10 months at concentration of 100 mg/l was studied. The earliest monocyte's reaction to ethanol exposure was the intensification of their interaction with lymphocytes. Cyclic changes in adhesive activity of monocytes from these rats were found, while the unfavourable alterations of cell surface structure increased with the amplifying of ethanol effect. PMID- 1893160 TI - [Experimental megaureter in dogs: modeling by "devitalization" of a segment of the ureter and features of the course]. AB - The method of experimental megaureter modelling in dogs that is based on the operative damage of the ureter segment is described. Obstructive megaureter was found in 100% of "devitalization" of the ureterovesical junction and in 59% of "devitalization" of the middle third of ureter. Progression of megaureter symptoms and reduction of evacuator-secretory function on the side of modelling operation without anatomical narrowing of the ureter lumen in 41% of experiments pointed to the actual role of the functional obstruction in pathogenesis of this hard syndrome. In vitro methods demonstrated the decrease of contractility of the "devitalized" fragments and also of above and below situated segments of megaureter. Urodynamic investigations showed the signs of the bioelectrical disturbance in the megaureter wall and the disorder in excitement and contraction of the megaureter, deterioration of the reactivity of the megaureter on the functional loading tests. PMID- 1893161 TI - [Changes in the peritoneum of the small intestine and diaphragm in experimental portal hypertension]. AB - Diaphragm and small intestine peritoneum morphology was studied in experimental portal hypertension in rats with the help of luminescent, transmission and scanning electron microscopy techniques. Structural organizations of these peritoneum portions and performance function were different: fluid transudation realized through the small intestine peritoneum and resorption occurred via diaphragm peritoneum. Morphological signs allowed to judge about the increasing of fluid transudation in abdominal cavity and diaphragmatic resorption in early period of portal hypertension. Morphological alterations appeared in peritoneum resorption sites (pumping diaphragmatic hatchs) according to progress of portal hypertension that indicated decompensation process of peritoneal fluid absorption and led to ascites. PMID- 1893162 TI - [Morphological characteristics of the pituitary-gonad system in high altitude hypoxia]. AB - The experiments on male rats showed that their sojourn at high altitude resulted in alterations of functional relationship between the gonadotropic pituitary cells and tests. That was characterized by synthesis inhibition and hormone release by gonadotropocytes. In the testes we found impairments in the barrier function and active substance transport in sustentocytes. Intensification of destructive processes in sustentocytes, with prolongation of adaptation duration, are mediated to a greater extent by a direct destructive high altitude factors. A decrease in hormone producing function of glandulocytes as a result of destruction processes has aggravated dysharmony of the pituitary-testes system which by the end of the second month was manifested by a marked inhibition of gonadotropic cell hormone release with preservation of the synthesis high level in them. PMID- 1893163 TI - [Stimulation of reparative osteogenesis by electromagnetic oscillations in the millimeter range in traumatic defects of the lower jaw in experimental animals]. PMID- 1893164 TI - [Ultrastructural changes in rectal mucosa cells in experimental Escherichia infection]. AB - Ultrastructural changes of rectum epitheliocytes and cells of lamina propria were studied at the period from 15 minutes to 2 days after inoculation using the model of experimental escherichiosis. The results obtained allow to determine the correlation of ultrastructural changes and the data of morphometric analysis. Ultrastructural peculiarities were determined of the rectum cells and the different cell populations were studied during infection's process. PMID- 1893165 TI - [Accumulation of lipofuscin granules in acute myocardial infarct as a model of cell aging]. AB - Electron microscopic investigation of lipofuscin granules (LG) accumulation during one month in the myocardium of young rabbits in case of experimental acute infarction was performed. Accumulation of LG in cardiocytes of the ischemia damaged myocardium area at the prenecrotic and necrotic stages was found. Analogous LG accumulation in cardiocytes in the perinecrotic area at the stage of infarction development was also observed. The fact of LG formation in fibroblast like cells was also established. Cardiocytes and fibroblast-like cells contain a set of ultrastructurally varying LG. LG formation in functionally different cells of the ischemia-damaged myocardium is a further evidence of the active metabolic role of this organelle suggesting a common principle in LG genesis. PMID- 1893166 TI - [Changes in the ultrastructure of nervous tissue cells under the effects of blood serum of patients with infantile cerebral paralysis in various modeling systems]. PMID- 1893167 TI - [Recovery of motor function after partial decortication under the effects of double gravitation]. AB - The motor function recovery was studied after surgical damage of the left motor cortex in albino rats in control and under double gravitation action for 20 and 40 min a day. Distance between the 1st and 5th finger was measured. The positive influence was shown on post-lesional recovery. PMID- 1893168 TI - [Effects of acute stress on lateralization of lipid peroxidation in the brain depend on the behavioral typology of rats]. AB - Using the "emotional resonance test" albino mongrel male rats were separated for their preference to light or dark space during the cry of a "victim" rat receiving footshock. Rats avoiding the cry of a "victim" by moving to the light space were characterized by higher levels of lipid peroxidation (LPO) products. A short footshock resulted in a dramatic LPO decrease in both hemispheres in the brain of all rats under study, but in rats not avoiding the cry of a "victim" (preferring dark space) "left" asymmetry of LPO increased. PMID- 1893169 TI - [High functional activity of mitochondrial creatine kinase of the myocardium before ischemia is tied with the worst restoration of contractility after reperfusion]. AB - Isolated Langendorff-perfused guinea pig hearts were arrested with a cardioplegic solution containing 10 mM phosphocreatine + 15 mM glutamate (PG group) or not containing them (control group). Total normothermic ischemia lasted 45 min followed by 30 min reperfusion. Mitochondrial respiration in the absence and presence of different concentrations of ADP and creatine was studied in biopsy samples after saponin treatment. The samples were taken before and after ischemia as well as after the reperfusion period. A slightly better relative recovery of developed pressure (RRDP) in PG group was associated with higher mitochondrial acceptor control ratio after reperfusion. When results in both groups were taken together, marked negative correlations between the preischemic mitochondrial indices (particularly, those related to creatine kinase activity) and RRDP were revealed. Relative changes in these indices after ischemia demonstrated tight positive correlations with RRDP. Thus, the hearts having higher functional activity of mitochondrial creatine kinase are more sensitive to ischemia, other conditions being equal. PMID- 1893170 TI - [Effects of adaptation to periodic hypoxia on bioelectric activity of cardiomyocytes of isolated heart in ischemia and reperfusion]. AB - Experiments on isolated Wistar rat heart perfused according to Langendorff showed that preliminary adaptation of rats to intermittent hypobaric hypoxia limited the fall of values of the resting potential and the amplitude and duration of action potential characteristic for ischemia. Under similar conditions, adaptation considerably reduced the increased time of impulse conduction along the myocardium. In reperfusion, the parameters enumerated restored much more efficiently in hearts from adapted animals than in controls. The role of these changes in the antiarrhythmic effect of adaptation to intermittent hypoxia is under discussion. PMID- 1893171 TI - [Effects of pantethine on metabolism in myocardial mitochondria under the conditions of deep hypothermia]. PMID- 1893173 TI - [Effects of volume and rate of blood loss on indicators of auto-hemodilution]. AB - The results of synchronous monitoring of blood impedance versus body impedance in dog experiments showed that the speed of physiological hemodilution related to blood loss up to 30 ml/kg is poorly dependent on the rate of blood loss (0.4-1.0 ml/kg/min) and averages 0.186 +/- 0.02 ml/min/kg. Termination of blood loss is followed by marked reduction in the rate of auto-hemodilution. In bloodletting the studies revealed a linear dependence between the volume of blood loss up to 30 ml/kg and tissue fluid volume entering the blood stream. In blood loss intestinal absorption of fluid does not block the fluid introduction from the interstice. When associated, both these flows increase volume of fluid filling vascular bed and promote stable recovery of the baseline circulating blood volume. PMID- 1893172 TI - [Measuring of intracellular Ca2+ concentration in macrophages. Effects of platelet activation factor]. AB - In experiments on mice resident and stimulated thioglycolate macrophages the changes in cytoplasmic Ca2+ concentration Ca2+ have been studied by the use of the fluorescent probe fura-2. PAF acether (10(-7) M) raised Ca2+ by 300-400 nM within 1 min only in the stimulated macrophages. In the resident cells this increase was much less. In the presence of 2mM EGTA, PAF raised Ca2+ to a lesser extent. This suggests that PAF causes influx of exogenous Ca2+ through the receptor-mediated channels as well as releasing Ca2+ from intracellular stores. PMID- 1893174 TI - [Change in inotropic and chronotropic function of the heart and resistance of the coronary vessels during combined use of Ca2+ antagonists]. PMID- 1893175 TI - [Peptide hydra morphogen activates Na/H-exchange in human erythrocytes]. AB - The effect of peptide morphogen of hydra (PMH) on Na+/H+ exchange in human erythrocytes was studied. It was shown that this peptide leads to 2-7 fold activation of the rate of protons efflux from the human erythrocytes at concentration 100 nM. It was assumed, that peptide controls and regulates proliferation via the activation Na+/H+ exchange. PMID- 1893177 TI - [Effects of tocopherol on functional reserves of phagocytes]. AB - The addition of alpha-tocopherol into rats died (4 mg a day during 7 days) brings a twofold increase in tocopherol content in blood plasma and 1,3 fold increase in peritoneal macrophages. Viscosity of membrane lipids of macrophages was decreased. Control and experimental macrophages had identical activity of oxygen dependent processes and ability for cholesterol esterification. PMID- 1893176 TI - [Effects of excess and deficiency of thyroid hormones in the body upon blood melatonin in pubertal male rats]. AB - Experiments have been carried out on Wistar line pubertal male rats in Winter. Radioimmunological method showed, that in intact animals the night peak of melatonin in blood was 994,36 +/- 195,99 pM/l, following ten-days intramuscular thyroxin injection (100 mg/100 g body mass)--2560,52 +/- 322,04 pM/1 and 20 days after, following bilateral thyroidectomy--117,13 +/- 16,35 pM/l, that totals 257,5% and 11,8%, respectively. Thus, the night peak of melatonin depends upon thyroid hormones concentration in blood. PMID- 1893178 TI - [Regulation of superoxide dismutase activity during deep hypothermia by simultaneous administration of water and lipid soluble antioxidants]. AB - Alongside anti-hypoxia activity, the method of deep hypothermia causes discoordination of metabolism in the heart. This is due to increased secretion of catecholamines in the process of cooling, to activation in free radical generation and lipid peroxidation. Pantethine and alpha-tocopherol were used. Pantethine reduced lipid peroxidation, preserved reaction activity of catalyzing resyntheses and transport of high energetic compounds in the heart, while alpha tocopherol prevented lipid peroxidation activation and decrease in SOD. Simultaneous use of pantethine and alpha-tocopherol caused increase in SOD and normalization of heart metabolism. Thus, for protection of the heart against excessive free radical generation under deep hypothermia simultaneous use of antioxidants like pantethine and alpha-tocopherol is necessary. PMID- 1893179 TI - [Modeling of blood drainage from the longitudinal sinus depending on the vessel bifurcation level]. AB - Simulation of hydrodynamic conditions in the brain showed the dependence of fluid drainage velocity on the bifurcation level of branching vessels. The conclusion was that acute angle of the longitudinal sinus bifurcation in different bio morphological groups of animals represented special features of the brain drainage in the brain in connection with life conditions. PMID- 1893180 TI - [Role of estrogens in the regulation of composition of bile acids of the enterohepatic system in rats and monkeys with extrahepatic cholestasis]. AB - Analysis of the thin-layer chromatography and gas chromatography data on the free and conjugated bile acid contents in the blood leaving intestine, hepatocytes and bile of ovariectomized rabbits and monkeys with acalculous cholecystitis revealed a heterogeneity of bile acid distribution in these biological media and an uniformity of specific alterations manifested in increased glyco-conjugation, decreased free bile acids in hepatocytes and blood, decreased cholesterol level and reduced lithogenic index of the bile. Results obtained are indicative of involvement of the gonadal steroids and estradiol dipropionate in regulation of bile acid conjugation in liver and, therefore, in development of one of the early factors of the gallstone formation. PMID- 1893181 TI - [A comparative study of lipid peroxidation activation after myocardial electro destruction and in the early stages of the development of myocardial infarct in experimental studies in dogs]. AB - Electric defibrillation counter shock impulses and AMI influence on lipid peroxide activation processes were conducted. The results showed insignificant lipid peroxide activation after defibrillation counter shock (200-300 J), while the same activation in first hours of coronary artery ligation was 1.4-1.5 times greater. We concluded that lipid peroxide activation products may be an appropriate method for AMI evaluation and prognosis. PMID- 1893182 TI - [New molecular mechanism of the blockade of neuronal N-cholinoreceptors]. AB - Antioxidants and disulphide bond reducing agents have shown the central N cholinolytic effect and prevented nicotinic-induced contraction of isolated smooth muscle preparation (ISMP). N-cholinolytic pediphen and antioxidant ionol reduced disulphide bond in the supernatant of mouse brain, but sulphydryl-oxidant agents 5'5-Dithiobis (2-nitrobenzoic acid) abolished N-cholinolytic effect of pediphen on ISMP. It is concluded that reduction of disulphide bond of N cholinoceptor is a molecular mechanism of its blockade. PMID- 1893183 TI - [Luminol and lucigenin-dependent chemiluminescence in 6-hydroxydopamine auto oxidation]. AB - It was shown by the methods of luminol- and lucigenin-dependent chemiluminescence that 6-hydroxydopamine 6-ONDA autooxidation is accompanied by generation of superoxide anion-radical which can further react with next 6-ONDA molecule. This fact is based on the observations that intensities of luminol- and lucigenin dependent chemiluminescence during 6-ONDA autooxidation was increased in aprotonic aqueous solutions (with the decreasing of pH) and was extremely depended on 6-ONDA concentration. The obtained data allows to suggest that one of the possible mechanisms of 6-ONDA neurotoxic action includes the generation of superoxide, whose dismutation to hydrogen peroxide in the presence of transient valency ions gives rise to HO. PMID- 1893184 TI - [Study of soluble proteins of mouse crystalline lenses (normal and in cataract)]. AB - The water-soluble proteins from mice lenses (normal and cataract lenses) were investigated by methods of absorption spectrophotometry and kinetics of UV induced radical decay. General characteristic of internal structure of extraction proteins was investigated by recombination kinetic method. It was shown that concentration of water-soluble proteins lowered ten times in lenses of mature cataract, i. e. 90% protein molecules were connected in lenses of mature cataract. PMID- 1893185 TI - [Experimental study of the effects of amiridin and tacrine on learning and memory]. AB - The authors studied the influence of amiridin and tacrine on learning and memory in mice and rat by passive avoidance conditioning test at norm and under scopolamine induced amnesia as well as of their effect on acetylcholine esterase (AChE) activity in brain cortex homogenates. Amiridin in doses 0.1 and 0.2 mg/kg showed a beneficial action on conditioning in untreated animals, its effect being comparable with that of piracetam. Tacrine was ineffective. In scopolamine treated animals amiridin and tacrine showed anti-amnestic action at dose of 0.1 mg/kg which was found ineffective with respect to AChE activity. The data suggests that the ameliorating effect of amiridin and tacrine on cognitive abilities in patients with senile dementia is not related their anticholinesterase properties. PMID- 1893186 TI - [Study of anti-amnesic activity of amiridin in a model of amnesic syndrome]. AB - The model of amnestic syndrome obtained by treatment with scopolamine during 20 days in rats was used to study anti-amnesic activity of amiridin in comparison with that of tacrine, physostigmine and piracetam. Multiple injection of Sc resulted in significant deterioration of rats, performance in passive avoidance test. Behavioral disorders were accompanied by such changes in lipid composition of brain synaptosomes which indicated a decreased membrane fluidity. Amiridin and tacrine as well as piracetam showed anti-amnesic action which in the course of treatment correlated with their normalizing effect on lipid content of synaptosomes. The diverse effect of amiridin and tacrine with respect to physostigmine implies that the former drugs can't be attributed to anticholinesterase preparations which are traditionally used in the treatment of Alzheimer disease. PMID- 1893188 TI - [Effects of opioid neuropeptides on the prostaglandin system and lipid peroxidation processes in the myocardium during stress-induced damage]. AB - The stress was subsequenced by lowering of Thromboxane A2 level and activation of peroxidation of lipids without any changes of prostacyclin content in myocardium. It was found that the pre-increase of the opioid peptides in blood plasma led to the absence of prostacyclin and thromboxane dynamic and myocardial lipids peroxidation inhibition during the subsequent stress. PMID- 1893187 TI - [Anti-stress effect of dalargin in immobilization stress in rats]. AB - The function of the isolated perfused rat hearts was studied in four groups of experiments. Group 1--included the hearts of intact animals ("absolute control"), group 2--the hearts of rats subjected to 24 hour immobilization in supine position against the background of triple intramuscular injections of placebo (control), group 3 included the hearts of rats, which during 24 hour immobilization stress were thrice injected a synthetic analogue of endogenous opioids Dalargin in a dose of 3 g/kg, and group 4 included the hearts of animals, which during immobilization were administered Dalargin in a dose of 10 g/kg of body mass. Ulcer index as indicator of stress injury of gastric mucosa was also determined. In the control group of experiments (group 2) 24 hour immobilization stress resulted in complete depression of cardiac performance as compared with group 1, and ulcer index approximated 1. In group 3 the indices of cardiac performance even exceeded those in group 1 (intact animals). As compared with group 2, ulcer index in group 3 decreased by 9 times. In application of Dalargin in a dose of 10 g/kg complete preservation of heart function indices and complete prevention of stress injury of gastric mucosa were also observed. Thus, Dalargin possesses cardioprotective and anti-ulcerogenic effect in immobilization stress in rats. Most probably, this phenomenon can be attributed to its ability to inhibit the activity of sympathoadrenal system, which gets enhanced during stress. PMID- 1893189 TI - [Effects of dalargin on hemodynamics of anesthesized rats during truncal vagotomy]. AB - I/v dalargin injection (20-25 g/kg) to narcotized rats in case of total myoplegia effectively protect hemodynamic changes under nociceptive stimulation. Bilateral truncal vagotomy partially decrease the protective effect of dalargin. Protective effect of the medicine results in activation of central and peripheral opioid receptors. PMID- 1893190 TI - [Combined action of anti-arrhythmia agents]. AB - A significant potentiation of antiarrhythmic effect was observed in 121 dogs with arrhythmias 24 and 48 hours after the coronary artery ligation when the following drugs were combined: N-propylajmaline bromide (1A class) and trimecaine (1B class), quinidine (1A class) and trimecaine, N-propylajmaline bromide and anaprilin (2 class). The potentiation is attributed to the different molecular mechanisms of action of the drugs. PMID- 1893191 TI - [Beta-lipotropin and beta-endorphin in compensation mechanisms of function after damage of the lateral hypothalamus]. AB - Possibility of restoration of food intake and other related functions impaired after lesion of lateral hypothalamus was studied on 45 male albino non-strain rats divided into 3 groups with 15 per each. Neuropeptides beta-lipotropin (beta LPT) and its derivative beta-endorphin were used as compensation factors. The parameters recorded were: volume of food and water intake, diuresis, body weight and temperature, frequencies of rest periods, comforting forms of behavior and orienting-exploratory activity. The results revealed that lesion of lateral hypothalamus resulted in the formation of specific central and peripheral syndrome responsible for the impairment of food intake and other related functions. Intracerebroventricular injections of beta-LPT and beta-endorphin facilitated compensation of impaired functions caused by lesion of lateral hypothalamus. The data were analyzed on the basis of the systems approach to the organism's physiological functions. PMID- 1893192 TI - [Use of dibunol in pharmacological correction of post-vagotomy hypoxia of digestive organs in rats]. AB - 1, 7, 14, 30 and 60 days after bilateral sub-diaphragmatic truncal vagotomy tension of oxygen (pO2) in liver, stomach and small intestine (jejunum) was determined. It was demonstrated that vagotomy leads to a decrease of pO2 in all investigated organs 1 day after the operation (such changes were observed in sham operated rats) and 30 days, in jejunum--after 7 days, in liver--after 14 days, in stomach--after 60 days. Dibunol introduction in vagotomized rats during 29 days (starting from the second day after operation) results in pO2 normalization in all investigated organs. PMID- 1893193 TI - [Complex assessment of the production of 3 variants of interleukin-1 by human peripheral blood monocytes]. AB - In vitro production of intracellular, membrane-associated and secreted interleukin-1 was investigated by peripheral blood monocytes from healthy donors. Activity of three IL-1 variants was assayed by the proliferation of responsive C3H/HeJ mouse thymocytes. Complex evaluation of IL-1 pools production by human PBM would provide a key to a better understanding of various diseases pathogenesis. PMID- 1893195 TI - [Experimental infection caused by Issyk-Kul' arbovirus]. AB - Experimentally in green monkeys, Syrian hamsters and white mice the authors studied the pathogenic properties of a new virus Issyk-Kul. The virus was determined in all animals--in blood and organs (brain, lungs, liver, spleen, kidneys). During the histological investigation the inflammatory and dystrophic injuries were established: in CNS, lungs, liver and kidneys. There was a distinct immunomorphological reaction in the spleen. The virus has pantropic properties and causes a generalized infection in animals. PMID- 1893194 TI - [Splenopentin--modulator of immunological and behavioral reactions in secondary immunodeficiency state induced by experimental alcoholism]. AB - Effect of splenopentin on some patterns of immunity was studied in mice with chronic alcoholic intoxication. Splenopentin was administrated into animals once intraperitoneally (250 micrograms/kg). Administration of splenopentin was found to normalize several immunological patterns in animals with chronic alcoholic intoxication: the immune response to the thymus-dependent antigen sheep red blood cells and phagocytic activity of peritoneal macrophages. Also observations over C57B1/6 mice characterized by high level of alcoholic motivation showed that alcohol consumption in mice decreased after administration of splenopentin at a dose of 250 micrograms/kg during two weeks. PMID- 1893196 TI - [Determination of antiplatelet antibodies on the surface of platelets by direct radioimmune method in patients with different types of immune thrombocytopenia]. AB - Direct radioimmune assay (RIA) have been developed for detection of antibodies associated wild platelet membrane. Platelets from 12 patients with idiopathic thrombocytopenic purpura (ITP) and 27 patients with chronic lymphocytic leukemia (CLL) (platelet count (100,000 in 1 microliters) have been tested. Antibodies on platelets surface have been detected in all 12 patients with ITP and in 21 patients with CLL. In 6 CLL patients the number of immunoglobulins associated with platelets surface does not increase control level. It is possible, that in some CLL patients development of thrombocytopenia is mediated not only by platelet associated antibodies but by other mechanisms, one of which can be linked with the depression of megakaryocytes growth in bone marrow. Direct RIA for measurement of antibodies on platelet surface detect antiplatelet antibodies with higher frequency than indirect enzyme-linked-immunosorbent-assay (ELISA), developed earlier for assessment of antiplatelet antibodies in serum. Increase of platelet count in CLL patients after steroid and cytostatic treatment correlated with the decrease of platelet surface associated antibodies. PMID- 1893197 TI - [Effects of taktivin on antibody-forming splenic cells in rats]. AB - The paper studied the effect of Taktivin on antibody forming cells of the spleen of Wistar rats which were injected in doses 0.5 Hg and 1.0 Hg. Infusions of Taktivin were made in 24 h and 72 h after antigen immunization. PMID- 1893198 TI - [Tumor progression as a factor of variability of diurnal rhythm of phosphorus metabolism in a tumor]. AB - In a transplanted lymphosarcoma of rats by means of Cosinor method we discovered rhythm of P32 inclusions with ultradian and circadian periods. In the course of tumor growth changes of spectrum of periods, amplitudes and acrophases of rhythms take place. These shifts are explained by the progression and clonal structure of neoplasms. PMID- 1893199 TI - [Production of antitumor cytostatic factors by nonactivated resident macrophages of the peritoneal cavity of Syrian hamsters]. AB - The production of soluble cytostatic (CS) factor(s) by nonactivated peritoneal resident macrophages (Mph) of Syrian hamsters was found with the use of susceptible spontaneously transformed in vitro cells of STHE cell strain. The CS factor was determined by two modifications of CS test: 1) incorporation of 3H-TdR to the nuclei of target cells and 2) direct determination of the number of cells in the wells. The selected in vivo highly malignant variant of STHE strain appeared to be resistant to CS factors Mph. PMID- 1893200 TI - [Thyroid hormones in the regulation of the proliferation of epithelial cells of the stomach gland]. AB - The control effects of thyroid hormones were registered in mice stomach gland epithelium. The growth fraction, rhythm, activity of proliferation changed differently in fundal and pyloric epithelium following increased level of thyroid hormones. PMID- 1893201 TI - [Protein mass in human cardiomyocytes does not correspond to gene content]. AB - Lack of proportionality between DNA and protein content has been revealed in the human cardiac myocytes. The proportion 2:4:8:16 was observed in DNA of di-, tetra , octa- and hexadeca myocytes while the protein content of the same cells was 2:3.5:5.2:7.2 in the inner layer, 2:3.5:6.5:8.9 in the central layer and 2:3.1:5.6:9.1 in the outer layer of the normal left ventricle. The protein content of myocytes of the same ploidy was higher in the inner layer than in other ones. PMID- 1893202 TI - [Effects of surgical removal of the Brunner's region of the duodenum on nutrient digestibility in rats]. AB - In 1.5 months after surgical ablation of duodenum of Brunner's region the digestibility of proteins, carbohydrates, lipids and minerals was investigated in Wistar male rats. Estimation was based on the measurement of consumed and excreted nutrients. The rats with a bypass gastroduodenal anastomosis and sham operated animals were used as a control. It was ascertained that Brunner's region of ablated rats showed a reduced proteins digestibility. Possible reasons for change established are being discussed. Participation of duodenal glands in digestion is suggested. PMID- 1893204 TI - [Characteristics of recovery process in kidney tubule epithelium of white rats with advanced mercuric chloride-induced necrotic nephrosis]. AB - Paraffin and semithin sections were used to study the peculiarities of recovery process in kidney tubules of white rats at various intervals (3 days to 5 months). Koss reaction for evaluation of calcium saline level was used after subcutaneous injection of large doses of sublimate (0.6 mg/100 g of b.w.). The study revealed the expressed destruction of tubules to be followed by rapid (3 days after nephrotoxin injection) calcification of cellular detritus. PMID- 1893203 TI - [Dynamics of the early process in the rat liver depending on the method of stopping blood and bile flow]. AB - The purpose of this study was to evaluate the rats liver wound healing after liver resection and treatment by the "hemostopan", glue (MK-8) and traditional method. Each bile- and hemostatic means was marked with evolution of the morpho functional changes at the liver wound tissue determined by the degree of the bile and hemostatic method injure. The time healing, liver cell proliferation, 02 disorder level, ultrastructural changes have been studied. This examination indicates that "hemostopan" is more preferable for processing of the liver wound. PMID- 1893206 TI - [Dynamics of wound healing of skin wounds produced by laser and scalpel in experiments]. AB - In this study in 90 rats the measured rate of healing, pO2 in sites of postoperative scar and histological specimen of identical excisional wounds produced by CO2-laser, scalpel and combination are compared. The data of healing laser wounds via scalpel ones show slow laser wound healing. We explain, this by inhibition of the inflammation phase due to diminishing macrophages migration into the wound. pO2 data in postoperative scar after laser and scalpel wounds show that laser thermal alteration does not influence CO2 regimen in the scar. PMID- 1893205 TI - [Effects of dosed sympathectomy on the development of adaptation-compensation reaction of C-cells of the thyroid gland and chromaffin cells of the adrenal glands in young rats]. AB - Using radioimmunological, morphometrical, electron microscopic and luminescent methods, comparative analysis of thyroid C-cells and adrenal chromaffin cells has been carried out at guanethidine sympathectomy in young rats. Significant decrease of functional activity of C-cells with concomitant hyperplasia of C cells population under blockade of sympathetic influences has been revealed. Compared to C-cells, adrenal chromaffinocytes of sympathectomized rats possess higher degree of structural-functional mobilization and are characterized by intensive secretion of catecholamines directed at restoration of tissue neurotransmitter deficit. PMID- 1893207 TI - New concepts bring new concerns about the combination natural teeth/implant arch. PMID- 1893208 TI - A new sinus lift procedure: SA-4/'O'. PMID- 1893211 TI - Locating the mandibular nerve: determine the predictable zone of safety. PMID- 1893210 TI - A new step-by-step approach: CeraOne single-tooth replacement. PMID- 1893212 TI - Basic underpinnings to sound implant techniques: soft tissue response to serviceable dental implants. PMID- 1893213 TI - Part 1: Esthetics in implant dentistry. PMID- 1893214 TI - Making space: relocation of neurovascular bundle yields available bone. PMID- 1893215 TI - Dental School of Copenhagen. AB - The Royal Dental College of Copenhagen, now a 101-year-old institution, has a yearly intake of around seventy students. The school is at the forefront of dental education in Europe with regard to facilities, research and curriculum development. PMID- 1893216 TI - Do dogs and cats need a dentist? AB - As man needs a dentist, also animals do. The author gives us some reasons for the treatment of animals, taking dogs and cats as an example. PMID- 1893217 TI - Who makes decisions about your future? AB - Dr. Backer has been the president of the Advisory Committee on the training of dental practitioners of the E.E.C. This committee is concerned with the quality of the training of dental practitioners. The goals of the Advisory Committee are explained and several topics like vocational training, introducing subspecialities, problems of the European dentist and assistant in dental care are being discussed. PMID- 1893219 TI - Natural killer cell activity is associated with brain asymmetry in male mice. AB - The brain is known to modulate the immune system in an asymmetrical way. In mice, there is an association between handedness and immune response and it has also been shown that hemicortical ablation has opposite effects on some immune parameters. An association between autoantibody production and paw preference was previously observed in female mice, but not in males, suggesting that the association between immune reactivity and functional brain asymmetry is a sex dependent phenomenon. In three independent experiments, natural killer (NK) cell activity, lymphocyte subset distribution, and mitogen-induced lymphoproliferation were assessed in male C3H/OuJIco mice selected for handedness and after unilateral cortical ablation. Handedness was shown to be associated with NK cell activity but not with lymphocyte subset distribution or lymphoproliferation. Left handers exhibited lower NK cell activity compared to right-handed or ambidextrous animals. In contrast to previous results in female mice, mitogen-induced lymphoproliferation was not associated with handedness in males. Left cortical ablations depressed NK cell activity, while right lesions had no effect. Neither left or right lesions affected lymphocyte subsets. No interaction between paw preference and side of the lesion was found in the modulation of NK cell activity. These and previous data show that the association between paw preference and immune reactivity varies according to the sex of the animal and the immunological parameters studied. This indicates that the brain may modulate different components of the immune system in different ways, through mechanisms apparently involving sex hormones. PMID- 1893218 TI - Major reproduction hormones as regulators of cell-to-cell interactions in humoral immune responses. AB - The effects of chorionic gonadotropin (CG), estradiol, and progesterone on the cell mechanisms that determine the rate of the humoral immune response have been investigated in experiments on ovariectomized and noncastrated mice. CG (40 IU) injected into noncastrated animals increased the antibody response to sheep erythrocytes (SRBC), whereas a higher dose of the hormone (200 IU) had no effect. In contrast, both hormone doses inhibited the immune response in ovariectomized animals. Injection of estradiol (2.5 micrograms/day), but not progesterone (0.2 mg/day), into ovariectomized mice stimulated the immune response, indicating a possible role of estrogens as mediators of CG immuno-stimulating effect in noncastrated animals. Both CG does inhibited suppressor cell generation in noncastrated mice, whereas in ovariectomized animals, the hormonal effect was directly opposite. Sex steroid hormones did not influence the formation of suppressor cells. In a syngeneic transfer system, the hormones under study did not change the activity of helper T cell precursors. However, CG administration to noncastrated recipients stimulated an adoptive immune response in a dose dependent manner. Estradiol, but not progesterone, has the same effect in ovariectomized mice. CG administration (200 IU) to ovariectomized recipients inhibited the plaque-forming cell response. This CG effect depended upon prostaglandin synthetase activity. PMID- 1893220 TI - Thymic peptides, stress, and depressive symptoms in older men: a comparison of different statistical techniques for small samples. AB - Thymic peptides play an important role in aging and immune regulation, but little is known about their relationship to psychosocial factors. One thymic fraction, thymosin-alpha 1 (TSN-alpha 1) may be of particular interest given its hypothesized role in the differentiation of immature T cells into functional, mature T cells. We examined the relationships among stress, psychological symptoms, and TSN-alpha 1 levels in two conditions; before and after a glucose challenge test. The sample consisted of 18 men, aged 48-80, participants in the Normative Aging Study. While none of the correlations reached significance in the baseline condition, life events and depressive symptoms were significantly correlated with TSN-alpha 1 in the postchallenge condition (r's = .57, and .62, respectively). Hierarchical regression analyses with cross-product interaction terms suggested that individuals who were high in both life events and depression showed the highest levels of postchallenge TSN-alpha 1, with the psychosocial variables accounting for 65% of the variance. Given the small sample size, we replicated these analyses using jackknife and bootstrap techniques, which generally confirmed these findings. Thus, these preliminary results suggest that psychosocial factors may be related to abnormal TSN-alpha 1 responses to a challenge. PMID- 1893221 TI - When OSHA calls. PMID- 1893223 TI - Foreign body office protocol. PMID- 1893224 TI - Grievence. PMID- 1893222 TI - Terminating a dental/patient relationship medical malpractice. PMID- 1893226 TI - Biology of methylotrophs. PMID- 1893225 TI - Systematics of methylotrophic yeasts. PMID- 1893227 TI - Heterologous gene expression in methylotrophic yeast. PMID- 1893228 TI - The phenomenology of religious psychopathology. AB - Patients with firmly established belief systems frequently enter analysis. The analyst must determine the extent to which neurotic and therefore analyzable components are involved in the patient's beliefs as such, as opposed to how the beliefs are embraced and adhered to as expressions of personal neurotic symptom formation or character pathology. The author discusses typical patterns of neurotic religious involvement as they are expressed clinically in hysterical, obsessional, depressive-masochistic, narcissistic, and paranoid modes and styles. He illustrates the manifestations of these patterns with clinical examples drawn from psychoanalytic experience. PMID- 1893229 TI - Instrumental narcissism in parents. AB - Instrumental narcissism is a syndrome manifested by parents who feel compelled to transform their infants and young children into geniuses. The parents' effort devalues the child's own abilities and exaggerates the parents' self-perceived magical powers. Various historical and contemporary examples of instrumental narcissism provide the basis for the author's exploration of the syndrome in the context of contemporary clinical discussions of narcissism. PMID- 1893230 TI - Post-Tarasoff legal developments and the mental health literature. AB - Since Tarasoff first established the duty of psychotherapists to warn or otherwise protect third parties when a patient is considered dangerous, the mental health literature has continued to address the two most controversial issues in that case: the questionable ability of clinicians to predict violent behavior, and the role of confidentiality in psychotherapy. The author examines recent trends in the law in light of this research and concludes that so-called anti-Tarasoff statutes recently passed by some states appropriately take into account the mental health literature and effectively balance competing public policy concerns. PMID- 1893231 TI - The Quality of Object Relations Scale. AB - The Quality of Object Relations Scale (QORS) provides a methodological and theoretical framework for personality classification based on relative level and quality of object relations. The authors believe that many available clinical assessment systems have little heuristic value, and propose that the QORS yields more meaningful descriptions of people. They discuss its theoretical basis in psychoanalytic object relations theory, and how its construction and rationale represent an attempt to incorporate recent thought relevant to the classification of personality. They include criteria for its organizational levels, prototypical vignettes, and a case demonstration. They also explore methodological issues relevant to clinical use and present reliability and validity data derived from empirical studies. PMID- 1893233 TI - Affect integration in psychoanalysis: a clinical approach to self-destructive behavior. AB - Self-destructive behavior can be an attempt to reverse self-fragmentation or breakdown secondary to feeling overwhelmed by unbearable affect. Therapeutic attention to blocks in the development of affect integration may help individuals process painful feeling states more efficiently, thus dealing with tension states more constructively. The author describes two cases that illustrate therapeutic removal of such blocks, followed by cessation of the self-destructive behavior and resumption of the normal developmental process. PMID- 1893232 TI - The abstinence of the psychoanalyst. AB - Complexities are inherent in the application of the psychoanalytic principle of abstinence. The author defines abstinence, presents a historical and current review of the concept, and describes circumstances, in the psychoanalytic field and in the public at large, that have led to its misinterpretation. Three vignettes illustrate the conflictual situations that abstinence presents to the analyst, as well as its constructive and ultimately gratifying results. PMID- 1893235 TI - Transactions of the Topeka Psychoanalytic Society. PMID- 1893234 TI - The uncomfortable community meeting and the privacy-urgency coordinate: discussion and case study. AB - The authors review the literature and describe factors contributing both to the value and to the discomfort of community meetings on an adolescent inpatient unit. The defensive use of an exaggerated estimation of meeting discomfort is discussed, and the concept of a "privacy-urgency coordinate," useful in analyzing group dynamics, is introduced. A case example illustrates the importance of balancing the need of patients for privacy with their need to resolve urgent problems on the unit. PMID- 1893236 TI - Living with AIDS. PMID- 1893237 TI - Prevention of toxemia of pregnancy in Ecuadorian Andean women: experience with dietary calcium supplementation. AB - Pregnancy-induced hypertension (PIH) is a significant cause of low birth weight and maternal and neonatal death around the world. This article reviews work indicating that dietary calcium supplementation can sharply reduce the PIH incidence among pregnant women whose regular diet is calcium-poor. It also describes physiologic conditions prevailing during pregnancy that could explain calcium's major role in PIH--as well as supplemental calcium's great potential for preventing PIH among people with low-calcium diets. PMID- 1893238 TI - The training and integration of village health workers. AB - This article describes the selection, training, activities, and supervision of village health workers (VHWs) in a rural area of Haiti. The aim is to provide an overview of work that may serve as a useful example to others engaged or wishing to engage in VHW programs. The account describes selection and training of the VHWs, relationships established between themselves and with other health team members, operation of the VHW program, and development of community pharmacies by the VHWs in their homes. PMID- 1893239 TI - Epidemiologic identification of infants with low birth weight in urban areas of Latin America: II. A simplified risk score for early prenatal identification in Guatemala City. AB - A simple, empirically derived instrument is needed in developing countries to identify mothers at risk of delivering low birth weight (LBW) infants, in order to help reduce the incidence of LBW deliveries and provide mothers at high risk with appropriate health care. The study reported here was devoted to developing an instrument of this kind using data obtained before the twenty-sixth week of gestation from an urban study population of 17,135 Guatemalan women. It appears that this instrument could be appropriately applied to urban populations in other developing countries. PMID- 1893241 TI - William Gorgas, soldier of public health. PMID- 1893240 TI - Maternal risk factors for low birth weight and intrauterine growth retardation in a Guatemalan population. AB - Hospital data on 306 mother-infant pairs in Coban, Guatemala, were studied to assess factors responsible for low infant birth weights involving the two general kinds of intrauterine growth retardation (IUGR), these being Type I (symmetric stunting) and Type II (asymmetric stunting or wasting). The results indicate that the Type I IUGR observed arose primarily from long-term poverty, malnutrition, and chronic poor living conditions, while much of the Type II IUGR seemed attributable to maternal disorders affected by short interbirth intervals. PMID- 1893242 TI - Role of nongovernmental organizations in health activities in Trinidad and Tobago. PMID- 1893243 TI - NMDA-, kainate- and quisqualate-stimulated release of taurine from electrophysiologically monitored rat hippocampal slices. AB - While excitatory amino acids (EAAs) are known to evoke the release of taurine in the hippocampus, we have found that taurine is localized primarily in dendrites and only to a lesser extent in terminals in this region. To determine whether taurine is released as a neurotransmitter by non-toxic concentrations of EAAs, or exclusively as a neuroprotectant in response to excitotoxicity, we monitored the release of amino acids from hippocampal slices during simultaneous electrophysiological recording in the CA1 region to assess tissue viability. N methyl-D-aspartate (NMDA) was the most potent of the EAA agonists tested for stimulating release of taurine. Exposure of slices to 120 microM NMDA increased the concentration of taurine in the perfusate to 1325% of its basal value. Kainate (KA) at a concentration of 128 microM increased taurine to 543% of baseline while quisqualate (Quis) at a concentration of 120 microM increase taurine to only 202% of its baseline value. Release of taurine in response to NMDA and KA peaked during the period when the concentration of the agonist was declining in the bath and did not return to its baseline value until 20 min after removal of the agonist. Increases in release of taurine were associated with concentrations of NMDA, KA, and Quis that caused an incomplete recovery of the CA1 field potential. These results suggest that taurine is primarily released by concentrations of glutamate receptor agonists that exhibit evidence of excitotoxicity in the CA1 region. PMID- 1893244 TI - Differential expression of protein kinase C isozymes in rat glial cell cultures. AB - Protein kinase C (PKC) is a family of closely related enzymes implicated in molecular processes involved in growth and differentiation in a variety of cells. We studied the presence and distribution of 4 PKC isozymes in glial cell cultures of the rat hippocampus employing antisera raised against synthetic peptides predicted from the cDNA sequences corresponding to the C-terminal portion of 4 PKC isoforms, alpha, beta I, beta II, and gamma. PKC(alpha) and -(beta II), but neither PKC(beta I) nor -(gamma) isoforms were detected in glial cultures of the rat hippocampus. Anti-PKC(alpha) immunostained all glial cells, whereas anti PKC(beta II) faintly stained about 20% of total glial cells resembling the type-2 astrocyte that were GFAP immunopositive, with few processes. Anti-PKC(beta II) did not stain about 80% of the glial fibrillary acidic protein (GFAP) immunopositive cells with a few thick processes which resembled the type-1 astrocyte. A few cells that stained intensely with anti-PKC(beta II) were GFAP immunopositive and possessed fine, but well-developed, multiple processes. Faint PKC(beta II) immunoreactivity was also detected among anti-MBP-positive cells (possibly oligodendrocytes), RCA-1-positive cells (possibly microglia), and small, oval, anti-GFAP-positive cells. These results suggest the involvement of distinct PKC isoforms in different glial functions. PMID- 1893245 TI - Electrophysiological properties of neurons in the rostral ventrolateral medulla of normotensive and spontaneously hypertensive rats. AB - Single unit activities were recorded from the rostral ventrolateral medulla (RVL) of pentobarbital-anesthetized normotensive Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Throughout the recording period, arterial blood pressures of WKY (mean arterial pressure, MAP = 103.1 mm Hg) and SHR (MAP = 159.2 mm Hg) remained stable at the respective basal levels. The units recorded in this study were all spontaneously active and cardiac-locked. Two types of discharge patterns, namely single and double discharges, were identified. These single and double discharge units were found to distribute randomly in RVL. In WKY, 92.6% of RVL neurons exhibited single discharges whereas in SHR, the majority (57%) of RVL neurons exhibited double discharges. The mean firing rate of single discharge units in RVL of SHR was significantly higher than that of WKY, whereas the mean firing rate of double discharge units in WKY was similar to that of SHR. About half of the units studied were also tested for antidromic collision; all units tested could be antidromically activated from the intermediolateral column (IML) of the thoracic spinal cord and the lowest threshold sites were consistently localized within IML. In both groups of rats, the axonal conduction velocity of RVL neurons showed a bimodal distribution viz. the fast and slow conducting axons. The mean conduction velocities of each of these two groups of neurons in WKY and SHR were similar. Most of the double discharge units in WKY and SHR belonged to the fast conducting type.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1893246 TI - 5,7-Dihydroxytryptamine injections increase glial fibrillary acidic protein in the hypothalamus of adult rats. AB - The distribution and levels of glial fibrillary acidic protein (GFAP) were determined in the adult rat hypothalamus following axotomy of serotonin (5-HT) neurons. Seven days after unilateral intrahypothalamic injection of the 5-HT neurotoxin, 5,7-dihydroxytryptamine, there was a marked increase in the number of GFAP-labelled astrocytes in the ipsilateral hypothalamus of 5,7-DHT-treated as compared to sham-treated rats. In addition, levels of GFAP were significantly increased 7 days after 5,7-DHT injection. PMID- 1893247 TI - Relationship of calbindin D-28k and cholinergic neurons in the nucleus basalis of Meynert of the monkey and the rat. AB - Double-labeling immunocytochemistry reactions were carried out in the monkey and the rat nucleus basalis of Meynert (NBM) to determine the extent of overlap between cholinergic neurons and neurons immunoreactive for calbindin-D-28k (CaBP), a Vitamin D-dependent calcium binding protein. The results indicate that most, but not all, NBM cholinergic neurons in the monkey are immunoreactive for CaBP. On the other hand, none of the rat NBM cholinergic neurons are immunoreactive for CaBP. PMID- 1893249 TI - Disappearance of xenogenic astrocytes transplanted into newborn mice is associated with a T-cell response. AB - Following transplantation of fragments of embryonic rabbit brain into the brains of newborn mice, the proportion of mice bearing detectable xenogenic astrocytes increases to over 80% in the first 3-4 weeks. Recent studies have demonstrated that the host response at this time was dominated by non-specific elements of host defense: macrophages, microglia and astrocytes. In the second phase, the proportion of mice bearing xenogenic astrocytes declines rapidly after 4 weeks and reaches zero by 10 weeks. In the present experiments, designed to characterize the host defense during this period, a dramatic increase in the proportion of mice displaying T-cells in the brain in the fourth and fifth weeks after transplantation was found. This corresponded with a marked decline of xenogenic astrocytes. Both subsets of T-cell, helper-inducer (L3T4) and cytotoxic suppressor (Lyt2), were found, with L3T4 more numerous in many samples. T-cells were found at the site of transplantation and at sites of migration. The division of the host-defense response in this model into a phase of antigen non-specific cells followed by a period when T-cells appear and transplanted astrocytes disappear, should facilitate kinetic studies into the mechanisms of brain-graft rejection. PMID- 1893248 TI - The CCK-A receptor antagonist devazepide but not the CCK-B receptor antagonist L 365,260 reverses the effects of chronic clozapine and haloperidol on midbrain dopamine neurons. AB - In this study, we examined the effects of the cholecystokinin-A (CCK-A) antagonist devazepide (MK 329) and the CCK-B antagonist L-365,260 to reverse the decrease in the number of spontaneously active dopamine (DA) cells in the ventral tegmental area and substantia nigra pars compacta after chronic haloperidol (HAL) or clozapine (CLOZ) treatment. The intravenous administration of devazepide (2 micrograms/kg) but not L-365,260 (2 micrograms/kg) reversed the reduction in the number of spontaneously active A9 and A10 DA cells produced by chronic HAL. Furthermore, devazepide also reversed the decrease in the number of spontaneously active A10 DA cells produced by chronic CLOZ administration. Overall, these results suggest that CCK-A but not CCK-B receptors play an important role in mediating or maintaining the chronic antipsychotic drug-induced effect on midbrain DA cells. PMID- 1893250 TI - Radial glia give rise to perinodal processes. AB - Nodes of Ranvier in the central nervous system in mammals are characterized by the presence of perinodal astrocytic processes. This study examines the association between processes of radial glia and the axolemma at nodes of Ranvier in the spinal cord of the mature axolotl, an animal in which radial glia represent a large portion of the total glial population. The radial glial cells have their cell bodies located close to the central canal. Those situated dorsal to the canal send long processes to the dorsal surface of the spinal cord. Along this trajectory these processes coalesce into large fascicles in the midline and form the dorsal median septum. Slender branches rise from the processes in these fascicles and extend into the adjacent white matter to terminate in close apposition to the axolemma at nodes of Ranvier. This arrangement provides an intracellular pathway extending from the perinodal region to the surface of the spinal cord. Radial glia ventral to the central canal give rise to processes that project to the glia limitans adjacent to the ventral spinal artery. These ventrally projecting processes appear to be more irregular in their branching pattern than their dorsal counterparts. Multiple slender processes are seen in close apposition to the nodal axolemma of myelinated axons in the ventral white commissure, again providing an intracellular pathway that runs from the perinodal region to the cord surface. In one instance a radial glial process was observed to occupy a pocket formed by the invagination of the nodal axolemma. The axonal cytoplasm adjacent to the invagination contained a variety of organelles, e.g. multivesicular bodies, vesicles and endoplasmic reticulum, suggesting that this relationship between the radial glial process and the axon is more than a passive interaction. These observations are consistent with the view that processes of radial glial cells may regulate the extracellular environment adjacent to the nodal axolemma, and/or play an active role in the maintenance of the nodal membrane. The existence of perinodally-directed processes of radial glial cells in the salamander indicates that this axo-glial specialization reflects an important functional interaction preserved across a large segment of the phylogenetic scale. PMID- 1893251 TI - Electroacupuncture in rats: evidence for naloxone and naltrexone potentiation of analgesia. AB - Low frequency electroacupuncture (EA) analgesia has been thought to be mediated by endogenous opioids. Among other lines of evidence, it has been reported that EA stimulation delivered at 2 and 2-15 Hz in rats could be blocked or partially antagonized by naloxone (NAL) and naltrexone (NTX). In contrast, experiments in one of our laboratories (D.J.M.) showed that NAL did not inhibit 2 Hz, and even potentiated 125 Hz EA analgesia. In an attempt to resolve these discrepancies, we conducted joint experiments in the U.S.A. and in China using the methods which previously yielded NAL reversibility of EA analgesia. In no experiment did opiate antagonists block or reduce EA analgesia. On the contrary, we found that, in most experiments, NAL and NTX potentiated 2 and 2-15 Hz EA analgesia respectively. The potentiation occurred independently of laboratory methods, geographic location of the experiment, strain (Chinese or American), tail temperature, sex, and weight of rats. This potentiation suggests the existence of an opioid anti-analgesic system or that NAL and NTX acquired analgesic properties following EA. These results indicate that EA analgesia in rats is a variable phenomenon even when laboratory methods are rigorously replicated. The EA stimulation may activate multiple conflicting neural circuits which interact and ultimately modulate the analgesic outcome. PMID- 1893253 TI - Electroacupuncture analgesia in naive rats: effects of brainstem and spinal cord lesions, and role of pituitary-adrenal axis. AB - Recent studies have shown that analgesia is potentiated by naltrexone (NTX) and naloxone (NAL) pretreatment in rats exposed for the first time to electroacupuncture (EA). In the present study, we have investigated the role of the pituitary-adrenal axis and of brainstem and spinal cord structures in EA analgesia and its potentiation by NTX. The pituitary and adrenal glands do not participate in the production of EA analgesia, but may produce a non-opioid substance which interferes with the development of EA analgesia. Spinalization or dorsolateral funiculi lesions blocked EA analgesia, and intrathecal NTX had no effect. These results indicate that supraspinal structures are necessary to produce and potentiate EA analgesia. Contrary to their critical role in morphine and other models of environmentally produced analgesia nucleus raphe alatus and raphe structures dorsal to it are not necessary for the development of EA analgesia. These structures, however, may contain opiate synapses on which NTX may act as an agonist to potentiate analgesia. The various components which appear to participate in the production of EA analgesia imply a complex circuit of pain modulation systems and indicate that an organism can adapt to distinct environmental conditions with versatile means to avoid pain. PMID- 1893252 TI - Electroacupuncture analgesia in rats: naltrexone antagonism is dependent on previous exposure. AB - Inhibition of pain by low frequency electroacupuncture (EA) has been thought to be mediated by endogenous opioids. We reported in a previous paper, however, that naloxone (NAL) and naltrexone (NTX) either potentiated or had no effect on analgesia in EA-naive rats, independent of origin (American or Chinese), sex, weight, geographic location (the U.S.A. or China), or numerous variations of experimental methodology. In the present study, we hypothesized that the number of exposures to EA treatment may be responsible for the discrepant effect of opiate antagonists. We found, as previously demonstrated, analgesia in EA-naive rats was potentiated by NTX. After two pre-exposures to EA, however, NTX antagonized analgesia. These results indicate that, in rats: (1) pre-exposure is a key variable for opiate antagonists to produce antagonism or potentiation of analgesia; (2) environmental cues paired with the initial analgesic manipulation may be responsible for converting analgesia from non-opioid to opioid, as already demonstrated with classically conditioned and learned helplessness induced analgesia; and (3) EA analgesia in rats is a multidimensional manipulation which can be influenced by subtle environmental changes. PMID- 1893254 TI - NMDA antagonists attenuate hypertension induced by carotid clamping in the rostral ventrolateral medulla of rats. AB - The purpose of these experiments were to study the interactions of N-methyl-D aspartate (NMDA) with baroreceptor reflexes induced by transient carotid clamping. Adult male Sprague-Dawley rats were anesthetized with urethane. Bilateral common carotid artery occlusion resulted in a reversible and reproducible hypertension in the vagotomized animals. This hypertensive reaction was blocked by intraventricular injection of NMDA antagonists, such as 2-amino-7 phosphono-heptaneoate (AP-7) and phencyclidine (PCP). We also found that blood pressure-sensitive neurons of the rostral ventrolateral medulla (RVLM) could be classified into two groups, on the basis of their responses to norepinephrine given intravenously. Using pressure microejection and single unit recording, we observed that clamping of the common carotids resulted in excitation of type I neurons. This evoked excitation, similar to that induced by NMDA, was blocked by locally applied AP-7. However, the carotid occlusion-induced responses of type II neurons were not blocked by AP-7. In conclusion, the present data suggest that NMDA receptors are involved in hypertensive responses during carotid occlusion, perhaps involving a site in the rostral ventrolateral medulla. PMID- 1893255 TI - Antinociception and behavioral changes induced by carbachol microinjected into identified sites of the rat brain. AB - The sites of the rat brain in which intracerebral administration of carbachol (0.4 microgram/0.5 microliter) elevates the nociceptive threshold to thermic (tail-flick test) and mechanical (calibrated-pinch test) noxious stimuli were examined. An extensive mapping (510 sites) ranging from AP + 10.5 to AP-0.1 mm revealed that antinociception was obtained from 119 sites (23%) widely scattered in the brain, and reached structures distant from, or within the immediate vicinity of the ventricular system. The effects from most placement were demonstrated using the tail-flick test, whereas a smaller proportion (approximately 13%) of sites was effective in reducing the response to mechanical stimuli only. Structures containing sensitive sites include the dorsal raphe nucleus, lateral border of the superior cerebellar peduncle, caudal portion of the superior colliculus, medial geniculate body, habenular complex, amygdala, temporal pole of the ventral hippocampus, rostral aspect of the dorsal hippocampus, lateral septal area, and triangular nucleus of the septum. Analysis of the distribution of responsive sites indicated that they are poorly superposed to the known distribution of opiate-sensitive areas. Most of the structures found to be responsive to carbachol are also known to possess cholinergic receptors and to evoke antinociception following focal electrical stimulation. In various placements, particularly in limbic structures, microinjection of carbachol evoked jumping to mechanical noxious stimulation, hyperexcitability to non-noxious stimuli, convulsive reactions, and other less frequent reactions. On few occasions, however, these changes were accompanied by antinociception. PMID- 1893256 TI - Morphometric study on the postnatal growth of the hippocampus in Australian Aborigines and Caucasians. AB - In an autopsy study on Australian Aborigines (29 males, 27 females) and Caucasians (57 males, 37 females) the postnatal growth of the hippocampus was studied and described by mathematical growth functions. For male adults no significant difference in hippocampal volume was found. In contrast, hippocampal volume was significantly smaller for Aboriginal females compared to Caucasian females. Growth analysis showed slower growth rates and later half-value times for Aborigines compared to Caucasians. These results are discussed in relation to secular changes of growth parameters of the human brain during the last century, the socioeconomic and health status of Aborigines, and sexual differences in development and plasticity of the hippocampus. PMID- 1893257 TI - Electrophysiological analysis of the ascending and descending components of the micturition reflex pathway in the rat. AB - Electrophysiological techniques were used to examine the organization of the spinobulbospinal micturition reflex pathway in the rat. Electrical stimulation of afferent axons in the pelvic nerve evoked a long latency (136 +/- 41 ms) response on bladder postganglionic nerves, whereas stimulation in the dorsal pontine tegmentum elicited shorter latency firing (72 +/- 25 ms) on these nerves. Transection of the pelvic nerve eliminated these responses. Firing on the bladder postganglionic nerves was evoked by stimulation in a relatively limited area of the pons within and close to the laterodorsal tegmental nucleus (LDT) and adjacent ventral periaqueductal gray. Stimulation at sites ventral to this excitatory area inhibited at latencies of 107 +/- 11 ms the asynchronous firing on the bladder postganglionic nerves elicited by bladder distension. Electrical stimulation of afferents in the pelvic nerve evoked short latency (13 +/- 3 ms) negative field potentials in the dorsal part of the periaqueductal gray as well as long latency (42 +/- 7 ms) field potentials in and adjacent to the LDT. The responses were not altered by neuromuscular blockade. Similar responses were elicited by stimulation of afferent axons in the bladder nerves. The sum of the latencies of the ascending and descending pathways between the LDT and the pelvic nerve (i.e. 72 ms plus 42 ms = 114 ms) is comparable although somewhat shorter (22 ms) than the latency of the entire micturition reflex. These results provide further evidence that the micturition reflex in the rat is mediated by a spinobulbospinal pathway which passes through the dorsal pontine tegmentum, and that neurons in the periaqueductal gray as well as the LDT may play as important role in the regulation of the micturition. PMID- 1893258 TI - Sterilising embryos for transgenic chimaeras. AB - 1. Experiments were undertaken to attempt to sterilise fowl embryos with ultraviolet light. Such sterilised embryos would be useful as recipients of genetically manipulated germ cells. 2. The germinal crescents of embryos were exposed to a calibrated UV source at stages 4 and 8 to 10 of incubation for 30 s, 3 min and 10 min. Teratological and sterility effects were studied at periods up to 6 d of incubation. 3. Simply exposing embryos by opening the shell produced a number of abnormalities and mortalities. These decreased with the age of the embryo but increased with the dosage of irradiation. 4. Although there was abundant evidence for UV-induced cell damage, the sterility of the embryos was usually less than 75%. PMID- 1893259 TI - Inbreeding and heterosis effects on quantitative traits in a White Leghorn population under long-term reciprocal recurrent selection. AB - 1. Inbreeding and heterosis effects for quantitative traits were estimated in two White Leghorn lines selected with reciprocal recurrent selection (RRS) since 1950. 2. Pedigreed progeny were produced from full-sib, half-sib and unrelated pure line as well as reciprocal cross line matings to estimate inbreeding and heterosis effects "within sires". 3. Inbreeding effects estimated as linear regressions agreed well with estimates considering inbreeding as fixed effect. The inbreeding depression per 10% inbreeding was highest for hatchability (6-7%), intermediate for production-related traits (3%), and about 1% for shell quality, body weight and egg weight. 4. Heterosis effects were estimated by comparing pure line and cross line progeny of the same sires. 5. Results indicate considerably less heterosis for egg production than found earlier, which is interpreted as a consequence of pure line selection. PMID- 1893260 TI - Utilisation of pearl millet (Pennisetum typhoides) for egg production. AB - 1. The performance of White Leghorn laying hens on diets providing pearl millet (Pennisetum typhoides) at 300 and 600 g/kg to replace maize, part per part, or "maize mix" isoenergetically and isonitrogenously in the first experiment and at 600 g/kg diet to replace maize in toto, part per part, in the second experiment were examined. In the first experiment, 3 groups of 12 laying hens were placed on each of the 5 dietary treatments for 3 x 28 d, whereas in the second experiment, each of the two diets was offered to 10 groups of 15 laying hens for 6 x 28 d. 2. Inclusion of pearl millet in the diet at the expense of maize, part per part, did not significantly influence hen-day egg production, feed intake, feed efficiency and body weight in either experiment. Incorporation of pearl millet isoenergetically at the expense of "maize mix" at any level, i.e. 300 g or 600 g/kg (Experiment 1), also did not influence hen-day egg production but at the end of periods 2 and 3 did result in decreased feed intakes with consequent improvements in feed efficiency. 3. Egg weight in general showed a tendency to improve with diets providing pearl millet at 600 g/kg. 4. Profits from egg sales over feed cost were directly proportional to the inclusion of pearl millet in the diet either at the expense of maize, part per part, or "maize mix" isoenergetically. PMID- 1893261 TI - Optimum isoleucine requirement of laying hens and the effect of age. AB - 1. Medium weight laying hens were used for an assay to determine their isoleucine requirement between 26 and 36 weeks of age and again between 46 and 56 weeks of age. 2. Two isoleucine-limiting mixtures were formulated with similar amino acid profiles, one containing 198 g and the other 110 g crude protein per kg diet. These mixtures were blended to give a series of 11 diets with isoleucine contents ranging from 7.6 to 3.8 g/kg. The lowest protein diet was also fed with a supplement of L-isoleucine. Each of the 12 diets was given to 5 groups of 24 laying hens. 3. The daily isoleucine requirement of individual laying hens was estimated to be 9.48 mg/g egg output plus 44.47 mg/kg body weight per day for the 1st period and 12.11 mg/g egg output plus 6.86 mg/kg body weight per day for the 2nd period. Calculated optimum intakes of isoleucine for various ratios of cost of input to value of output are tabulated. For example, for a flock of medium weight hens producing an average of 50 g daily egg mass, the optimum isoleucine intake (mg/hen d) varied between 760 and 890 varying for ratios of costs to egg prices. 4. It is concluded that the isoleucine required per day does not decrease during the first laying year despite a decrease in rate of egg output. PMID- 1893262 TI - Bone strength of caged layers as affected by dietary calcium and phosphorus concentrations, reconditioning, and ash content. AB - 1. The effects of preconditioning, dietary calcium and phosphorus concentrations, ash content, body weight, and bone geometry on the shear strength of the radius of caged layers were investigated. 2. Birds that did not lay for three or more weeks before the end of the production period had higher radius bone strengths than the birds producing eggs. 3. Shear breaking force increased with bone ash content. 4. The shear breaking force and stress of the radius were not affected by increasing dietary calcium and phosphorus during the last 8 weeks of production. 5. Freezing and thawing before testing had no effect on bone strength. 6. Body weight cannot be used to predict the breaking force of the radius of caged layers. PMID- 1893263 TI - Increasing hatchability of turkey eggs by injecting eggs with pyridoxine. AB - 1. In field trials, eggs from two flocks of Large White turkey hens were injected with about 0.2 ml saline solution containing 600 micrograms of pyridoxine hydrochloride in order to examine its effect on hatchability. 2. Also, in an aseptic laboratory trial, eggs from Large White turkey hens were injected with 0.2 ml of saline solution and 0.2 ml of saline solution containing 600 micrograms of pyridoxine hydrochloride. 3. In field trials, hatchability of pyridoxine injected eggs was 4.6% higher (P less than 0.05) than the control (non-injected) eggs. 4. In the aseptic laboratory trial, hatchability of pyridoxine-injected eggs was 4.2% higher (P less than 0.05) than saline-injected and control (non injected) eggs. PMID- 1893264 TI - Effects of high concentrations of dietary vitamin E and ethoxyquin on the performance of laying hens. AB - 1. Three experiments were carried out with light strain laying hens to evaluate the effects of relatively high doses of dietary vitamin E (125 mg/kg food) or ethoxyquin (EQ) (250 mg/kg food) on their laying performance. The control diet contained 5 and 125 mg/kg vitamin E and EQ, respectively. The experimental diets were fed either from one or 32 weeks until 88 or 89 weeks of age. 2. The two antioxidants did not affect the growth of the pullets, age at first egg, final body weight, average egg weight or relative abdominal fat pad size and liver weight at the termination of the experiments. In two out of three experiments, vitamin E and EQ did not affect egg production, food efficiency or mortality; in the third experiment vitamin E significantly (P less than 0.05) improved egg production and food efficiency after an outbreak of Newcastle disease which occurred at 34 weeks of age. EQ significantly reduced mortality during the course of this experiment, but did affect the variables of performance. In two experiments vitamin E consistently improved shell density, although a significant effect was observed in only one of the eight determinations carried out. EQ did not affect this variable. 3. The uterine muscle was more susceptible to oxidation than the drumstick meat, as evaluated by TBA values. In both tissues, vitamin E significantly and consistently decreased TBA values and restricted their increase during incubation, while EQ was less effective, particularly in the drumstick meat. 4. It is concluded that increasing vitamin E and EQ concentrations in diets of laying hens have no effect on the decrease in egg production due to aging. However, vitamin E may minimize the decline in egg production and food efficiency following the outbreaks of some diseases and slightly improve--under certain yet undefined conditions--shell density. PMID- 1893266 TI - Self-selection of dietary protein and energy by turkey breeder hens. AB - 1. An experiment was conducted to determine the effects of self-selection of dietary protein and energy by turkey hens on reproductive performance in a warm environment. 2. Dietary self-selection had no significant effect on egg production, egg weight, or body weight of turkey hens. 3. Fertility and hatchability of eggs produced by self-selecting hens were significantly reduced compared to eggs from control hens fed on a complete diet. 4. Protein intake was significantly reduced among self-selecting hens when compared to control hens fed on a complete diet (P less than or equal to 0.001). 5. Food and energy intake decreased as the ambient temperature increased. Nevertheless, protein intake of self-selecting hens increased over the course of egg production despite decreasing food intake. Therefore, self-selecting hens preferred a diet with a greater protein content (g protein/kg diet) in the last 10 weeks of egg production than during the first 10 weeks of egg production. PMID- 1893265 TI - Effects of supplemental ascorbic acid on performance, organ weight and plasma cholesterol concentration in broilers treated with propylthiouracil. AB - 1. Four experiments were conducted to determine if dietary ascorbic acid (AA) affects body weight gain, food intake, organ weights, plasma cholesterol concentration, and ascorbic acid concentration in the plasma and liver of growing male broilers treated with an antithyroidal agent, propylthiouracil (PTU). 2. In the first experiment, 15 mg AA was administered daily into the crop of chicks fed on a diet supplemented with or without PTU (500 mg/kg). Administration of AA reduced plasma cholesterol concentrations in the PTU-treated chicks. 3. In the other three experiments, chicks were given the basal diet or an AA-containing (3 g/kg) diet supplemented with or without PTU (250 mg or 500 mg/kg). Feeding AA partly prevented the decreases in body weight gain, gain:food ratio and weights of the bursa of Fabricius and thymus in chicks fed on the 250 mg/kg PTU diet, and also prevented the increase in plasma cholesterol concentrations in chicks fed on the PTU diet. 4. These results suggest that AA improves the performance of chicks with experimentally induced hypothyroidism. PMID- 1893267 TI - The effects of dietary fat and bird age on the weights of eggs and egg components in the laying hen. AB - 1. A low-fat diet or an isoenergetic and isonitrogenous high-fat diet containing 55 g maize oil/kg were fed to laying hens at different stages during the laying year in two experiments. 2. Feeding the high-fat diet to young hens resulted in a rapid increase of 2.5 g in egg weight, made up of increases in both yolk and albumen weights. 3. Switching the diets at 50 weeks caused changes in egg weight that were accounted for entirely by changes in egg albumen weight. 4. Feeding the high-fat diet from 46 weeks in a second experiment increased egg and egg albumen weights by 1.26 and 1.34 g respectively. 5. The increase in egg weight with age was associated with a greater increase in the proportion of yolk, at the expense of albumen, compared to egg weight increases related to dietary fat. 6. It is concluded that dietary fatty acids increase egg weight by a mechanism different from that causing age-related increases in weight and that the mechanism involves a stimulation of oviduct protein synthesis. PMID- 1893268 TI - Pharmacokinetics of chloramphenicol in normal and Escherichia coli infected chickens. AB - 1. Disposition kinetics were compared in healthy chickens and in chickens naturally infected with E. coli following the intravenous, intramuscular and oral administration of chloramphenicol in a single dose of 20 mg/kg body weight. 2. Lower serum chloramphenicol concentration in diseased chickens were reported after intravenous injection, but they were higher than normal 30 min after intramuscular and oral administration. Following intravenous injection the volume of distribution was increased in diseased chickens. 3. The biological half-life in normal chickens was 8.32 +/- 0.5 h and was prolonged in diseased birds (26.21 +/- 0.2 h). The body clearance of chloramphenicol was reduced in diseased chickens. 4. The rate of absorption of chloramphenicol was delayed after administration via the oral route but the extent of absorption was increased. The maximum concentration was higher and it was reached after a longer time in diseased than in normal chickens after administration by both intramuscular and oral routes. PMID- 1893269 TI - Effect of intrahypothalamic injections of norepinephrine and serotonin on plasma arginine vasotocin and mesotocin in the White Leghorn cockerel. AB - 1. Saline (10 microliters), norepinephrine (NE) and Serotonin (5-HT), 500 nmol each, were injected into the anterior third ventricle (A3V; n = 7) or the posterior third ventricle (P3V; n = 11) of ananesthetised, unrestrained White Leghorn cockerels. Plasma arginine vasotocin (AVT) and mesotocin (MT) were measured 20, 60 and 120 min after injection. 2. Injection of NE into both the A3V and P3V had no significant effect on either plasma AVT or plasma MT at any of the sampling times. 3. Administration of 5-HT into the A3V significantly increased plasma MT about two-fold 20 min following injection. At 120 min time, plasma MT returned to normal. 4. In P3V birds, 5-HT had no effect on plasma MT in the first 20 min, but a significant increase in plasma MT occurred 60 to 120 min after injection. The magnitude of the response was lower than in the A3V cockerels. 5. Plasma AVT was not affected by 5-HT administration into the A3V at any of the sampling times, but 5-HT administration into the P3V caused significant rises in plasma AVT at 120 min. 6. Serotonergic, but not noradrenergic, induction of neurohypophysial peptide secretion was demonstrated. PMID- 1893270 TI - Sexual differentiation of copulatory behaviour in the male chick requires gonadal steroids. AB - 1. Embryonic injections of 0.3 mg/egg of tamoxifen (TAM), 0.2 mg/egg CI-628 (both antioestrogens), 0.5 mg/egg (ATD (aromatisation inhibitor), or antibodies to oestradiol (E), all suppressed male copulatory activity (MCA) in young male chicks. 2. Embryonic injections with either flutamide (F, androgen antagonist) or high dose of antibodies to testosterone (T) only slightly suppressed MCA. 3. TAM had no effect on embryonic plasma LH levels, 24 and 48 h after injection. 4. It seems that at the embryonic stage oestradiol is required for the normal differentiation of MCA. PMID- 1893272 TI - Age and exercise effects on mitochondrial density and capillary fibre ratio in bird leg muscle. AB - 1. Muscle fibre composition, capillary-fibre ratio and mitochondrial density of the Iliotibialis lateralis muscle were monitored during growth from the age of 8 weeks to sexual maturity (24 weeks) in sedentary birds and in birds subjected to regular treadmill exercise. 2. The Iliotibialis lateralis muscle consists almost exclusively of type IIA and IIB fibres with a small percentage of "unclassified" fibres. Over the 16-week period of growth there was no change in fibre composition but a marked fibre hypertrophy linked with a fall in the capillary fibre ratio. Mitochondrial volume density increased with age but this was not significant. 3. Exercise significantly increased the IIA:IIB fibres ratio from 0.77 to 1.1 but had no significant effect on any other measured characteristics. 4. It is concluded that exercise at the intensity and duration employed (10-15 min daily, ca. 70-80% maximum oxygen consumption) has little effect on the growth and development of avian skeletal muscle although there was evidence of an increased oxidative capacity of the muscle. PMID- 1893271 TI - Concentrations of hormones, glucose, triglycerides and free fatty acids in the plasma of broiler chickens selected for weight gain or food conversion. AB - 1. The concentrations of growth hormone (GH), insulin-like growth factor I (IGF I), thyroxine (T4), triiodothyronine (T3), reverse-triiodothyronine (rT3), triglycerides (Tri), free fatty acids (FFA) and glucose (Glu) were determined at 2, 4 and 6 weeks of age in blood plasma of male and female chickens of broiler lines selected for body weight (GL) or food conversion (FC). 2. Plasma concentrations measured in the same animal over a 24 h or a 2 week interval were not significantly correlated with each other. For different traits measured in the same plasma sample only the correlation between T4 and rT3 differed significantly from zero. 3. All traits were dependent on age. Line and sex effects were significant (P less than 0.05) for GH, T4, Tri, FFA and Glu. Additionally, line significantly influenced the plasma T3/T4 ratio and sex influenced plasma rT3. Interactions between line, sex and/or age were seldom significant. 4. Within line and sex, GH (at 6 weeks of age) and T3 (at 4 weeks of age) were negatively, and IGF-I and Tri (both at 6 weeks of age) positively correlated with the amount of abdominal fat at 6 weeks of age. No significant correlation between body weight at 2, 4 or 6 weeks of age and any of the plasma traits was found. PMID- 1893273 TI - Rumen digestive physiology and microbial ecology. AB - The rumen is a dynamic, continuous fermentation compartment that provides a suitable environment for a variety of species of anaerobic bacteria, protozoa, and fungi. These microorganisms have a complex series of interactions with the feeds supplied to the host, with some using particulate matter as both sources of nutrients and sites of sequestration to avoid being washed from the rumen by the rapid flow of fluids. Because of the ability to use soluble nutrients and to reproduce rapidly, other microbes associate primarily with the liquid phase of the rumen contents. Due to the metabolic activity of all microbial populations, feeds are converted to microbial matter and fermentation end products, which serve as nutrients for the ruminant. Optimum feed utilization by ruminants is dependent on achieving maximum rumen fermentation and flow of microbial protein to the duodenum. At this time, it is clear that the major nutrients required by the microbial populations include both fibrous and nonfibrous sources of carbohydrates and nitrogen in the form of ammonia, amino acids, and peptides. In spite of five decades of research, the exact quantities and sources of these nutrients that will result in optimum rumen fermentation rates and microbial yields are only partially known. PMID- 1893274 TI - Dairy nutrition management. PMID- 1893276 TI - Protein and amino acid nutrition of lactating dairy cattle. AB - This article describes the National Research Council Model of protein metabolism and illustrates its use in meeting the protein requirements of lactating cows. Attention is then directed toward amino acid nutrition with emphasis on the need for models to estimate amino acid requirements. Finally, the potential to improve productivity with rumen-protected amino acids is considered. PMID- 1893275 TI - Lipid nutrition. AB - Cows in early lactation or producing more than 80 lb of milk per day need supplemental fat and can benefit from it. Fat should be added to the diet over a period of several weeks to allow the cows to become accustomed to it. Feed intake should be monitored because additional fat may decrease feed intake and offset the benefit of the fat. Supplemental fat should not exceed 4 to 5% of the dry matter intake. The first 2% of added fat should be supplied by oilseeds under most circumstances. The next 1 or 2% can come from commodity fat if availability and handling ability permits its use. If the last increment of fat is needed, it should be supplied by specialty fats that have been processed to improve ruminal inertness. Extra calcium, magnesium, and ruminally undegraded protein should be added to the diet when fat is added. Fat is a more expensive source of energy than feed grains in most of the world and should not be used beyond needs. PMID- 1893278 TI - Fat-soluble vitamin nutrition for dairy cattle. AB - The need for supplementation of dairy cow diets with fat-soluble vitamins depends on the amount of vitamins naturally present in the diet, the availability of dietary vitamins, and the vitamin utilization rate of the animal. Fresh forage contains ample amounts of the vitamin A precursor beta-carotene as well as vitamin E. Irrespective of the dietary amount, however, the availability of vitamins A, D, and E, as well as beta-carotene, can be adversely influenced by poor fat digestion, as commonly occurs due to enteric disease in young calves. In addition, high-grain diets appear to increase the amount of ruminal vitamin destruction and may thus increase vitamin requirements. The vitamin utilization rate may be increased by inflammation as well as dietary and environmental factors. The factors influencing vitamin availability and utilization rate should be considered when formulating rations. Because the vitamin requirement is variable, blood concentrations of vitamins should be monitored when conditions such as poor fertility, weak calves, and poor immune response are present. PMID- 1893277 TI - Mineral and water nutrition. AB - In providing minerals to dairy cattle it is important to distinguish between dietary requirements and feeding recommendations. The requirement is the absolute amount of an element needed to meet the animal's metabolic needs for maintenance, growth, pregnancy, and lactation divided by the coefficient of absorption; this is estimated by the factorial method. Actual estimates of requirements for lactating dairy cattle have been determined for Ca and P. The major difficulties in relying on the requirement estimate are that dry matter intake varies and the true absorption coefficient of the mixture of feeds in the ration generally is unknown. Therefore, feeding recommendations, based on feeding graded concentrations of an element, often offer more applicable information. With the exception of Ca and P, the current feeding recommendations for the other macrominerals, Mg, Na, K, Cl and S, have resulted from feeding trials. With certain environmental and physiologic situations the feeding recommendations may vary. For example, during heat stress the dietary K recommendation for the lactating cow should be higher than in cool weather because of increased sweating and decreased feed intake. Another example may be that the source of supplemental Mg may affect what dietary inclusion rate will yield optimal performance and should be recommended. An important consideration in dairy ration formulation in the future will address the interrelationships of the various macrominerals. There is accumulating evidence that shows that different concentrations of Na, Cl, and K may interrelate and affect lactational performance. Many times the naturally occurring concentrations of one or more of these elements may have to be associated with varying concentrations of the others in order to optimize animal performance and health. Much experimentation likely will examine these interrelationships in the future. Supplementation of trace elements in diets of dairy cattle is common practice. This is because the quantities found in common feedstuffs are relatively low relative to the animal's needs and vary considerably among and within feeds. Supplementation provides a safety margin against potential deficiency. The reader is cautioned to consult other publications regarding potential interactions among the trace elements and their interactions with other nutrients. Potential oversupplementation is a real concern. Maximum safe tolerance concentrations for most trace elements are available. Water is the most important indispensable nutrient. Water requirements are affected by physiologic state and rate of milk yield, body weight, rate of dry matter intake, Na intake, and average minimum environmental temperature. Practically, offering a fresh, abundant supply of easily accessible drinking water at all times is essential.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1893279 TI - Management of the dairy herd treated with bovine somatotropin. AB - Cows that produce large quantities of milk require more management and higher quality of management than cows producing smaller quantities of milk. This is true whether improvements in milk production occur through genetic selection, increased milking frequency, or use of bovine somatotropin (bST). The milk response to use of bST is similar (10 to 15%) to that of three times a day (3x) milking and we expect that the management required to maintain the increased production through successive lactations with bST will be similar to that required for the 3x herd. Maximum economic benefit from use of bST will be achieved by dairy managers who (1) feed cows to maximize intake of diets with appropriate nutrient content and balance, (2) maintain proper body condition of their cows, and (3) have health and reproduction management programs that prevent rather than cure problems. Efficient use of record-keeping systems that enable the manager to monitor individual cow status will be advantageous. Economic forces will continue to bring change to the dairy industry. The manager that plans for change and ensures that the dairy's management programs allow for the most economically efficient production will be in position to adapt to these changes. The well-managed dairy will be able to adopt new, efficiency-enhancing technologies, such as bST, to ensure the continued opportunity to compete in the dairy industry. PMID- 1893280 TI - Grouping management and physical facilities. AB - Grouping management is one of the most important activities on the farm. It requires careful assessment of the daily routine on the farm and the development of a grouping/feeding management plan as well as a management plan that includes prioritization of the needed changes. If a good job is being done in this area, the cows will be more likely to respond to good nutrition. PMID- 1893281 TI - New approaches to nutritional monitoring. AB - This article discusses new and innovative methods that can be used in the field to assess the economic value of ingredients in the production system. Methods to evaluate and monitor milk production responses are considered. PMID- 1893282 TI - Nutrition and reproduction in dairy cows. AB - Diagnosis of nutritional effects on herd fertility requires a systematic analysis of reproductive records in addition to quantifying the feeding program on the farm. Corroborative laboratory tests for specific deficiencies may be useful. PMID- 1893283 TI - Feed additives. AB - Feed additives used to supplement dairy rations can increase daily feed cost from 2 to 65 per animal. The economic response (benefit to cost ratio) varies from $2.00 to $12.00 for each dollar invested in a specific additive. Knowledgeable dairy veterinarians must understand the role of each additive, when it will be beneficial, inclusion level, strategies and limitations associated with an additive, research and field recommendations, and measurable responses to monitor. Dairy additives and various methods to evaluate their role and economic response objectively are discussed. PMID- 1893284 TI - Ration formulation using linear programming. AB - A combination spreadsheet-LP ration formulation program offers tremendous advantages for dairy nutritionists. The spreadsheet format provides the framework for flexibility in describing feeds and in formulating a realistic and practical ration. The LP module can solve for a complicated set of nutrient requirements to give a relatively well-balanced ration. This "first-cut" ration can then be reworked in the spreadsheet mode to meet the needs of the individual farm based on other biologic and management considerations. PMID- 1893285 TI - Preruminant calf nutrition. AB - This article has attempted to give the reader an outline of the principles involved in preruminant calf nutrition together with a practical understanding of milk replacers and their use for raising calves. While the nutrient requirements of the preruminant calf are reasonably well understood, the complex interactions occurring when attempting to replace milk proteins with high levels of nonmilk proteins are clearly not well understood. Further, the management and environmental interactions on nutrition are profound and far from elucidated. PMID- 1893287 TI - Dry cow nutrition. The key to improving fresh cow performance. AB - Evidence supports the concept of the dry period being a critical component to lactation preparation rather than an insignificant rest period between lactations. Required nutrient amounts for the dry cow are the sum of maintenance, pregnancy, and reserve replenishment needs with additional requirements for growth during the first two pregnancies. Maintenance energy requirements can be dramatically increased by level of activity and adverse environmental conditions. A wide variety of feed ingredients can be successfully fed to dry cows as long as rations are appropriately formulated to meet energy, protein, mineral, and vitamin requirements. A early and close-up dry program best matches increasing pregnancy requirements and declining intake capacity with management capabilities. The early dry cow ration is formulated for high fiber/low energy density while the close-up ration contains higher energy density with less fiber. Both rations contain sufficient other nutrients based on determined intake. This two-group system provides maximal flexibility in managing for optimum body condition at calving. Environmental stresses and dramatic dietary changes should be minimized during the transition period from late gestation to lactation. A sound dry cow program results from integration of quality nutrition and cow management practices as described. A dry cow program that enacts these guidelines should result in reduced incidence of clinical mastitis, successfully complete pregnancy with a viable calf, maximize genetic potential for milk production, minimize incidence of health disorders, and allows cows to breed back within an economically optimum time interval. Overall, a sound dry cow program is a critical key to improved fresh cow performance. PMID- 1893286 TI - Replacement nutrition management. AB - The basic principles of dairy cow feeding apply equally to the dairy heifer. Ration balancing must be accomplished in order to formulate least-cost, nutrient balanced rations for each age group of heifers. Forage testing enables rations to be developed that utilize the various quality forages that are available on a farm and allows optimum allocation of forages for maximum profitability of the farm feeding system. In addition to feeding management, housing, ventilation, health care, grouping, cleanliness, and many other management factors can complement a sound heifer nutrition program. PMID- 1893288 TI - Implementation of nutritional consultation within a dairy practice. AB - Expansion of services to include nutritional consulting for client herds is a realistic expectation of most dairy practices. In addition to a client base, a commitment to obtaining the knowledge and an expertise in dairy nutrition is necessary. Once some expertise is gained, the most important requirement becomes regarding nutritional advice as an integral part of the practice and devoting the time to provide the service. Most implementation failures result from imprecise estimates of dry matter intake or a failure to maintain an ongoing presence on the farm and monitor results. PMID- 1893290 TI - Clinical usefulness of serum tartrate-resistant acid phosphatase in Paget's disease of bone: correlation with other biochemical markers of bone remodelling. AB - Tartrate resistant acid phosphatase (TRAP) has been proposed as a new biochemical marker for bone resorption. We have compared this new marker, TRAP, with the classical biochemical markers of bone remodelling, serum alkaline phosphatase (sAP), serum osteocalcin (sBGP), and with the urinary hydroxyproline/creatinine ratio (uOHProl/creatinine), a routine marker of bone resorption. Serum TRAP was significantly higher in pagetic patients (n = 43) than in control subjects (n = 12) (13.02 +/- 4.7 vs 5.48 +/- 1.31 IU/L, P less than 0.001) and a significantly positive linear correlation was found between the sTRAP and uOHProl/creatinine ratio (y = 0.0051x - 0.0069, r = 0.82, P less than 0.001), between sTRAP and sAP (y = 19.3x - 85.0, r = 0.71, P less than 0.001) and also between sTRAP and sBGP (y = 0.02x + 2.23, r = 0.52, P less than 0.01). Serum TRAP levels were higher than the upper limit of normality in all our pagetic patients except for two, whose uOHProl/creatinine levels were in the normal range. We conclude that (1) sTRAP could be a parameter as sensitive as uOHProl/creatinine in the diagnosis of Paget's disease; (2) sTRAP and uOHProl/creatinine are both good markers of bone resorption; (3) the correlation found between sTRAP and formation markers (sAP and sBGP) makes sTRAP a marker of disease activity in Paget's disease of bone; (4) the assay of sTRAP is easier, faster, and of lower cost than the urinary hydroxyproline determination. We suggest that sTRAP determination could be used as a routine marker of bone resorption in Paget's disease of bone, as is the case with uOHProl determination. PMID- 1893289 TI - Age, time since menopause, and body parameters as determinants of female spinal bone mass: a mathematical model. AB - The study of mathematical models to describe bone mass behavior throughout life is a possibility for assessing the main factors of peak bone mass and bone loss. We developed a mathematical model to predict spinal bone mass behavior on a sample of 181 healthy Italian women whose lumbar bone mineral content was determined by Gd-153 dual photon absorptiometry. This model proved to be both efficient, showing the best fit (r = 0.7 on spinal bone mineral content) when compared to other previously suggested models, and also reliable as its fit remained the best when applied to a subsequent sample of 519 women whose lumbar spine was measured by dual X-ray photon absorptiometry. This model suggests that body height and body weight (but not age) are determinants of bone mass in premenopausal women. In postmenopausal women, an accelerated phase of bone loss starting at menopause is dependent on age and time since menopause, whereas body mass index acts as a protective factor. This model confirms the influence on spinal bone mass not only of age and time since menopause but also of body size parameters. PMID- 1893291 TI - Synthetic human calcitonin in postmenopausal osteoporosis: a placebo-controlled, double-blind study. AB - A placebo-controlled, double-blind study was carried out over 4 months to evaluate two doses of synthetic human calcitonin (0.25 and 0.125 mg) given s.c. three times per week. Enrolled were 60 women, aged 56-82 years, who had experienced a vertebral fracture due to low-energy trauma within the preceding year. During active treatment there was within the first month a dose-dependent decrease of the indices of bone resorption (fasting urinary calcium and hydroxyproline excretions), whereas only the higher dose and a treatment period of 4 months produced a reduction of bone formation (serum osteocalcin). The bone mineral content (BMC) of the nondominant forearm was unchanged. Treatment with calcitonin also had significant, dose-dependent, analgetic effects. The amelioration of pain was, in multivariate analyses, related to a reduction in parameters felt to be markers for bone resorption. In the placebo group there was a significant reduction of the BMC of the forearm but no changes of any of the biochemical markers for bone turnover and no improvement of pain. In conclusion, treatment with two low doses of calcitonin induced changes of the biochemical markers of bone turnover in a dose-dependent manner. The analgetic properties of calcitonin were also of salient clinical importance. The knowledge derived from this study could be adapted to the dosage schedule in long-term trials in osteoporosis. PMID- 1893292 TI - Subchondral bone in osteoarthritis. AB - To determine whether subchondral bone in osteoarthritis differs from that seen in normal human aging, osteoarthritic femoral heads removed for total hip arthroplasty were compared with normal age-matched and young autopsy controls. Standardized, 1-cm deep, weight-bearing and nonweight-bearing subchondral bone blocks, as well as cancellous core bone, 2-4 cm deep on the articular surface, were examined in each femoral head. Mineralization was assessed using density fractionation and chemical analysis, and compared to histomorphometry. In osteoarthritis, both weight-bearing and nonweight-bearing surface subchondral bone showed a lower degree of mineralization than age-matched and young controls. Histomorphometric analysis showed that subchondral bone thickness, as well as all osteoid parameters and eroded surfaces, were increased in osteoarthritic samples versus controls. Mineralization in the deep cancellous core bone increased with normal aging but underwent less change with osteoarthritis. Histomorphometry of the cancellous core showed that osteoid parameters, but not bone volume, were increased in osteoarthritis versus controls. In conclusion, osteoarthritis is associated with a thickening of the subchondral bone with an abnormally low mineralization pattern. PMID- 1893293 TI - Chondroprotective action of salmon calcitonin in experimental arthropathies. AB - To assess whether calcitonin exerts an influence on cartilage, three models of arthropathies in rabbits--representing three different modes of cartilage destruction--were used: (1) corticosteroid administration (endocrinological disturbances model); (2) meniscectomy (mechanical stress model); and (3) immobilization of the hind leg (nutritional disorder model). After 12 weeks of methylprednisolone (MP) administration, the rabbit femur heads displayed cartilage erosions, marked decrease of glycosaminoglycans (GAG) content, and narrowing of joint spaces. Elevation of serum uronic acid, activity of alkaline phosphatase, and calmodulin content was evident. All these changes were minimal- close to normal--in the group treated for 12 weeks with MP + salmon calcitonin (sCT). Partial meniscectomy and hind leg immobilization caused statistically significant loss of GAG from the cartilage and narrowing of the knee joint space during the same experimental period, 12 weeks. In both these models the groups of rabbits treated simultaneously with sCT showed only insignificantly smaller joint spaces and GAG content. These results support our hypothesis of a chondroprotective property of calcitonin. However, the mechanism through which calcitonin influences joint cartilage remains unknown. A direct effect of calcitonin on cultivated chondrocytes, as well as the role of calmodulin, beta endorphins, calcium, and interleukin-1 in the process are discussed. PMID- 1893294 TI - Normal bone particles are preferentially resorbed in the presence of osteocalcin deficient bone particles in vivo. AB - In an in vivo model of osteoclastic bone resorption, we previously showed that osteocalcin-deficient bone particles (BPs), derived from warfarin-treated rats, were resorbed 50% as well as normal BPs and that they recruited fewer osteoclastic cells with decreased tartrate-resistant acid phosphatase (TRAP) activity. In order to determine the specificity of the resorption response, we evaluated the fate of implanted mixtures of normal and osteocalcin-deficient BPs. Normal and warfarin-treated donor rats were prelabeled in vivo with oxytetracycline to permit identification of BPs from either source. Normal, osteocalcin-deficient, and 50:50 mixtures of BPs (either labeled or unlabeled) were implanted into normal rats and recovered 12 days later for enzymatic (TRAP) and nondecalcified histomorphometric analyses. The incorporated oxytetracycline had no significant effect on resorption of bone particles. The recovered osteocalcin-deficient BPs were surrounded by fewer osteoclastic cells, were resorbed less, and contained less extractable TRAP activity than normal BPs. In mixed BP implants with normal and osteocalcin-deficient BPs, each type of bone particle elicited the same tissue response as when implanted separately. Remarkably, the different particles evoked dissimilar osteoclastic responses and were resorbed to different extents, even when adjacent within the same implant. These data suggest that osteocalcin may act as a substrate signal for resorption and that osteocalcin in the normal BPs does not influence the cellular response to adjacent osteocalcin-deficient BPs. PMID- 1893295 TI - Hydrochlorothiazide inhibits parathormone-stimulated increase in plasma tartrate resistant acid phosphatase in mice. AB - The inhibitory effect of hydrochlorothiazide (HTZ) on parathormone-induced bone changes in mice was studied with the aid of the analysis of plasma calcium and tartrate-resistant acid phosphatase. We have found that HTZ alone had no effect on plasma tartrate-resistant acid phosphatase (Tr-ACP), phosphate, and creatinine concentration. Parathormone (PTH) administration increased plasma Tr-ACP from 15.00 +/- 1.50 to 20.62 +/- 2.35 U/liter in intact mice. The increase of plasma Tr-ACP in HTZ-treated mice after PTH administration was not significant. The plasma calcium was affected in a way similar to Tr-ACP. HTZ reduced the sensitivity of bone to resorbing effects of PTH, using Tr-ACP as a useful biomarker of bone resorption. PMID- 1893296 TI - Structural changes of the periosteocytic area in Vipera aspis (L.) (Ophidia, Viperidae) bone tissue in various physiological conditions. AB - Microradiographs of ribs and vertebrae of the snake Vipera aspis, over an annual cycle, show a significant enlargement of the osteocytic lacunae in the winter months and, for the breeding females, during the period of embryo development. This enlargement is due to resorption of bone substance (periosteocytic osteolysis). The objection that such morphological findings could as well be explained by the formation of new, larger osteocytes derived from recent osteoblasts does not apply to the present animal model. No internal bone remodelling occurs during the annual seasonal cycle and therefore no new osteoblasts would have differentiated to osteocytes in the interior of the bone. In the vertebrae, an additional process is indicated as an area of decreased mineral density, termed demineralization halo, around the periosteocytic lacunae. An electron microscopy study suggests that this process of demineralization is not the first stage of periosteocytic resorption, but an additional process of demineralization. Thus, both osteolysis and demineralization halos in the perilacunar osteocytic region of the bone tissue represent reversible biological processes mediated by the osteocytes. PMID- 1893298 TI - Oxidative modification of lipoproteins--impact on atherosclerosis. PMID- 1893299 TI - Atrial thrombi revisited. PMID- 1893297 TI - Diverse forms of stress result in changes in cellular levels of osteonectin/SPARC without altering mRNA levels in osteoligament cells. AB - The osteonectin/SPARC gene has been shown to possess motifs for a heat shock element and metal responsiveness. Also, the expression of the protein has been associated with culture stress in endothelial cells. In the present study, osteoligament (OL) cells derived from the patellar ligament were subjected to diverse forms of stress that included (a) exposure to sodium arsenite, (b) heat shock, (c) cadmium ion, and (d) the amino acid analog, AZC. Osteonectin/SPARC levels in OL cells were determined by Western blot analyses, and immunoprecipitation using antiosteonectin antibodies. Expression of osteonectin/SPARC mRNA was determined by Northern analysis using a 1.5 kb EcoRI restriction fragment of bovine osteonectin cDNA. These studies reveal that osteonectin/SPARC is produced following diverse forms of stress, however, the levels are lower than observed in unchallenged OL cells. In all instances, the mRNA levels were comparable to control cells. These studies indicate that expression of osteonectin/SPARC mRNA is tightly controlled in OL cells and that the protein may be regulated at the level of protein translation. PMID- 1893300 TI - Echocardiographic detection of pulmonary emboli-in-transit. AB - Echocardiography can detect pulmonary emboli-in-transit as mobile masses within the right heart. In this case report, a patient with biventricular failure had both transthoracic and transesophageal echocardiograms which revealed a thromboembolus entrapped within the right atrium. Surgery confirmed the echocardiographic findings. PMID- 1893301 TI - Angiosarcoma of the heart. AB - A 17-year-old boy presented with severe chest pain which partially subsided on anti-inflammatory medication. Five week later he was admitted with fully developed cardiac tamponade. Within five days surgical exploration revealed an nonresectable right atrial tumour. Management of angiosarcoma of the heart is discussed. PMID- 1893302 TI - Absence of post exercise hypotension and sympathoinhibition in normal subjects: additional evidence for increased sympathetic outflow in borderline hypertension. AB - OBJECTIVE: In young men (mean age 25 years) with borderline hypertension the authors have documented a reduction in systolic blood pressure and muscle sympathetic nerve activity 60 mins after 45 mins of submaximal treadmill exercise. The aim of this study was to determine if post exercise hypotension occurs in normotensive young men, and if so, if it is accompanied by a decrease in sympathetic nerve activity. DESIGN: Replicating a previous protocol, the authors recorded blood pressure, heart rate, plasma noradrenaline and muscle sympathetic nerve activity (microneurography; peroneal nerve) before and 60 mins after submaximal treadmill exercise. SUBJECTS: Ten healthy male volunteers (mean age 28 +/- 5 years). INTERVENTION: Forty-five minutes of treadmill exercise at 70% of resting heart rate reserve. MAIN RESULTS: In contrast to borderline hypertensive subjects, prior exercise had no effect on either systolic or diastolic blood pressure or muscle sympathetic nerve activity in healthy volunteers. Plasma noradrenaline concentrations were similar before and after exercise. Resting heart rate (56 +/- 3 versus 70 +/- 3 beats/min; P less than 0.002), and sympathetic burst frequency (10 +/- 4 versus 20 +/- 2 bursts/min; P = 0.026) were lower in normal than in borderline hypertensive men. CONCLUSIONS: At rest, discharge to muscle sympathetic nerves is increased in young borderline hypertensive men; and blood pressure and sympathetic nerve activity are decreased after exercise in borderline hypertensive but not normotensive men. These observations suggest that the depressor response to prolonged rhythmic exercise in young men with borderline hypertension may be due in part to transient suppression of augmented central sympathetic outflow. PMID- 1893303 TI - Mitral valve replacement: mechanical versus bioprosthetic valves--a clinical review. AB - A review of the literature was conducted in an attempt to justify the exclusive use of either mechanical or tissue prostheses in the mitral position. In addition, the University of Toronto experience with mitral valve replacement was reviewed, including a five year follow-up from the Toronto General Hospital. Both studies concluded that there was no significant advantage for the use of either type of valve based upon freedom from thromboembolism, freedom from anticoagulant related hemorrhage and freedom from all valve-related mortality/morbidity. Tissue valves were shown to be significantly poorer substitutes in terms of freedom from primary valve failure (P less than 0.05) and freedom from reoperation due to valve-related complications (P less than 0.07). The clinical results from the Toronto General Hospital correlated with those reported in the literature and suggested the preferential use of mechanical valves during mitral valve replacement based primarily on their durability and a consequent lesser need for reoperation. PMID- 1893304 TI - Cardiac effects of prazosin in chronic aortic insufficiency. AB - Eight patients with chronic moderate to severe aortic insufficiency were assessed by radionuclide angiography at rest and during maximal bicycle exercise after six weeks of placebo, six weeks of prazosin titration up to 10 mg bid and 12 weeks of prazosin maintenance therapy. Prazosin was well tolerated and the final dose amounted to 18.6 +/- 0.7 mg/day. Exercise performance tended to increase (from 8.9 +/- 1.1 to 9.6 +/- 0.8 mins). Resting and exercise blood pressure and heart rate were not affected by prazosin. Left ventricular volumes were decreased and exercise ejection fraction increased by prazosin. Total left ventricular output decreased, whereas regurgitant index improved. The authors conclude that in patients with chronic moderate to severe aortic insufficiency, chronic prazosin therapy causes persistent improvements in left ventricular anatomy and function both at rest and during exercise. PMID- 1893305 TI - Fine structural alterations in radiofrequency energy-induced lesions in dog hearts: possible basis for reduced arrhythmic complications. AB - OBJECTIVE: To define fine structural changes in canine myocardium due to radiofrequency energy; to compare these changes with those due to direct current shock; and to determine if differences found can explain the reduction in arrhythmic complications observed following the use of radiofrequency energy. ANIMALS: Ten mongrel dogs were used for radiofrequency energy and seven for direct current shock experiments. DESIGN: Twenty-five Joules of direct current and 150 to 300 J of radiofrequency energy were delivered via catheters to the myocardium of anesthetized dogs. The endomyocardium was excised and processed for electron microscopy. MAIN RESULTS: The endomyocardial damage produced by radiofrequency energy and direct current shock was similar at the light microscopic levels. Ultrastructurally, the myocyte changes were similar but the supporting vasculature was better preserved in the direct current-damaged myocardium. CONCLUSION: The lack of vascular preservation in radiofrequency energy-induced damage compared to direct current shock myocardial damage may provide a morphological background for the reduced arrhythmic complications noted. PMID- 1893306 TI - Recommendations for physician training in Doppler echocardiography. PMID- 1893307 TI - Bedside nursing/hospital information system integration must include productivity gains for nursing. PMID- 1893308 TI - Implementing an automated care planning system in a nursing curriculum. PMID- 1893309 TI - A nursing service--education model for introducing baccalaureate nursing students to research and computer concepts. AB - Knowledge of core content of nursing research and computer technology is increasingly required of baccalaureate students. This article describes a teaching model that incorporates computer technology content within a baccalaureate nursing research course. The model uses thirteen (13) linking concepts to reinforce learning about both content areas throughout the course. PMID- 1893311 TI - Effectiveness of a geriatric day hospital. PMID- 1893312 TI - Informed consent to HIV antibody testing. PMID- 1893310 TI - The effectiveness of computer-managed instruction versus traditional classroom lecture on achievement outcomes. AB - This controlled experimental study examines the effect of two teaching methods on achievement outcomes from a 15-week, 2 credit hour semester course taught at two midwestern universities. Students were randomly assigned to either computer managed instruction in which faculty function as tutors or the traditional classroom course of study. In addition, the effects of age, grade point average, attitudes toward computers, and satisfaction with the course on teaching method were analyzed using analysis of covariance. Younger students achieved better scores than did older students. Regardless of teaching method, however, neither method appeared to be better than the other for teaching course content. Students did not prefer one method over the other as indicated by their satisfaction scores. With demands upon university faculty to conduct research and publish, alternative methods of teaching that free faculty from the classroom should be considered. This study suggests that educators can select such an alternative teaching method to traditional classroom teaching without sacrificing quality education for certain courses. PMID- 1893313 TI - Toward comprehensive cancer management in Canada: lessons from the United States. PMID- 1893314 TI - Chronic-pain patients must cope with chronic lack of physician understanding. PMID- 1893315 TI - Medical texts for the Third World. PMID- 1893316 TI - Through a glass darkly. AB - After graduating from the University of British Columbia (UBC) Dr. Gibson entered McGill University to study medicine but interrupted his studies to go to Oxford University (as a demonstrator in physiology), where he received his doctorate. He resumed his medical studies at McGill University, graduating in 1941. After serving in the clinical investigation units of the Royal Canadian Air Force (RCAF) he became deputy director of medical research at the RCAF headquarters in Ottawa. This was the post he held when he wrote the editorial "Medical education for 1980," which is reprinted as our Encore selection for this issue, starting on page 665. After the war Dr. Gibson worked at the Montreal Neurological Institute until 1948 and then by a circuitous route went on to UBC as Kinsmen professor of neurologic research. Following a sabbatical year in Marseille in 1958, he was appointed professor of the history of medicine and science at UBC, a post he held until 1975. His "retirement" has hardly been quiet. He has been chairman of the Universities Council of British Columbia and from 1985 to 1991 chancellor of the University of Victoria. PMID- 1893317 TI - Periodic health examination, 1991 update: 4. Screening for cystic fibrosis. Canadian Task Force on the Periodic Health Examination. PMID- 1893318 TI - Treatment of chronic asthma in children: the changing role of inhaled corticosteroids. Allergy Section, Canadian Paediatric Society. PMID- 1893319 TI - Adverse reactions to the preschool (fifth) dose of adsorbed diphtheria-pertussis tetanus vaccine in Canadian children. AB - OBJECTIVE: To quantify accurately the rate of adverse reactions after the preschool (fifth) dose of adsorbed diphtheria toxoid-pertussis vaccine-tetanus toxoid (DPT) vaccine and to test the hypothesis that large local reactions are attributable to the diphtheria toxoid. DESIGN: Double-blind randomized controlled trial. SETTING: Suburban community public health unit. PARTICIPANTS: Healthy children 4 to 5 years of age with a history of having received four doses of adsorbed DPT vaccine. INTERVENTIONS: Subjects were given either the standard DPT vaccine (with 25 Lf units of diphtheria toxoid) or a modified DPT vaccine (with 10 Lf units of diphtheria toxoid). They were assessed 24 hours later by a nurse. Serum samples obtained before vaccination were tested for diphtheria and tetanus antitoxin levels by means of neutralization assay and enzyme-linked immunosorbent assay. MAIN OUTCOME MEASURES: Rates of large local reactions (an area of redness or swelling or both of 5 cm or greater) 24 hours after vaccination in the two groups. Relation between serum antitoxin levels before vaccination and the rate of large local reactions in each group. RESULTS: Of the 250 subjects enrolled 124 received the standard vaccine and 126 the modified one. Large local reactions occurred in 71% of the subjects receiving the standard vaccine and 52% of those receiving the modified one (p less than 0.01). In the former group large erythematous reactions occurred significantly more often in those with an elevated prevaccination diphtheria antitoxin level than in those without an elevated level; no relation was found between such reactions and the prevaccination tetanus antitoxin level. Reduced arm movement was evident in 45% of the children in the two groups. Few had systemic adverse reactions. CONCLUSIONS: Large local reactions occur frequently after the preschool administration of the DPT vaccine. These reactions are uncomfortable but not serious. They result in part from the large amount of diphtheria toxoid in the standard DPT vaccine. PMID- 1893320 TI - Cerebral venous sinus thrombosis presenting as idiopathic intracranial hypertension. PMID- 1893321 TI - Use of oral poliovirus vaccine for unlicensed indications. PMID- 1893322 TI - Familial combined hyperlipoproteinemia. PMID- 1893323 TI - Medical education for 1980. 1945. PMID- 1893324 TI - Kurdistan provided interesting classroom for Canadian military doctors, medical assistants. PMID- 1893325 TI - China is now moving towards the Western way of death. PMID- 1893326 TI - Teaching and learning during a visit to China. PMID- 1893328 TI - Rearfoot surgery. PMID- 1893327 TI - Surgical approaches of the rearfoot and ankle. AB - The number of alternative approaches for the variety of rearfoot and ankle procedures commonly performed is clearly as great as the imagination of the surgeon. To ensure that the incisional approach is to contribute to the overall success of the procedure, the right approach must be selected and properly performed. To facilitate this process, general principles of incision placement and performance in the rearfoot and ankle have been presented. Building on those principles, one can learn the various techniques, as well as their respective advantages and disadvantages. Finally, the discerning surgeon should be able to apply the information presented here to select and perform the right incisional approach. Furthermore, the same process may lead the surgeon to improvise and create a successful alternative. PMID- 1893329 TI - Fixation devices in rearfoot surgery. AB - Numerous advances in biomaterials and fixation devices have improved the caliber of rearfoot surgical procedures. An understanding of the underlying physical properties of fixation devices along with the improvement in surgical technique have elevated complex foot surgery to a higher level of quality with improved results. Since the addition and continued improvement of rigid fixation to tarsal arthrodesis, more consistent osseus fusion with a decrease in nonunion has been found. PMID- 1893330 TI - Bone grafting in rearfoot surgery. AB - Bone grafting, especially in rearfoot surgery, is occasionally required. Two main morphologic types of bone may be grafted, namely cortical and cancellous. Each type of bone has its unique characteristics, which, when used properly, will ensure a good surgical result. Other factors also play an important role in decision making when using bone grafts. These factors include the characteristics of the host and site into which the graft will be placed, the fixation of the bone graft site, the metabolic state of the host, and the function of the graft. If careful surgical planning is exercised, a successful surgical result can be expected. PMID- 1893331 TI - Synovectomy-arthroplasty as an alternative to triple arthrodesis in the management of subtalar joint pain. AB - Subtalar joint synovectomy-arthroplasty represents an intermediate intervention between more traditional conservative and surgical techniques. Localization of pathology to the structures of the subtalar joint is essential. The likelihood of operative success is predicted by a prolonged remission of symptoms following the injection of steroid and local anesthesia within the subtalar joint. The procedure reduces pain and swelling while increasing ambulatory capacity. No appreciable increase in subtalar joint motion occurs. PMID- 1893332 TI - The tarsal tunnel syndrome and its surgical decompression. AB - This article addressed the tarsal tunnel syndrome. Its etiology, symptomatology, diagnosis, treatment, and surgical decompression were discussed. PMID- 1893333 TI - Surgery of the Achilles tendon and posterior muscle group. AB - Ankle equinus is defined as an inability to dorsiflex the foot at the ankle a minimum of 10 degrees with the knee in full extension. Numerous causes have been presented, and proper evaluation and diagnosis is critical before a surgical procedure can be selected. Gross spastic contractures will be managed differently than the more subtle forms of limitation of ankle dorsiflexion. Lastly, it should be remembered that the desired increase in range of motion will be accompanied by a decrease in strength of the posterior group, which will vary with the procedure and age of the patient. PMID- 1893334 TI - Surgical treatment of posterior tibial tendon dysfunctions. AB - Ruptures and dysfunctions of the tibialis posterior tendon are often overlooked or misdiagnosed and can cause considerable loss of function to the patient. This article reviews the etiology, clinical as well as radiologic diagnosis, classification, and alternative surgical approaches. Case reports and photography of magnetic resonance imaging examples are included as well as a description of flexor digitorum longus tendon transfer in the treatment of this disorder. PMID- 1893335 TI - Subluxing peroneal tendons. An anatomic approach. AB - Chronic subluxing peroneal tendons represent an interesting presentation of pathoanatomy. An appreciation for the local anatomic considerations about the distal fibula as well as the pathologic relationships that occur during these painful syndromes is critical to understanding this condition. An anatomic approach to repair chronic subluxating peroneal tendons is presented. A literature review is included to reinforce the success of the procedure in multiple trials and in various clinical situations. PMID- 1893336 TI - Lateral ankle stabilization. Modified Lee and Chrisman-Snook. AB - Chronic lateral ankle instability is not always a severe disability, but surgical reconstruction may be necessary in patients with instability or when conservative measures fail. Although recent articles by Ahlgren and Larsson and Bergsten et al provide evidence of satisfactory results with late ligamentous repair of chronic ankle instability via imbrication, lateral ankle stabilization procedures that use tenodesing of fasciodesing techniques continue to provide good results. Prolonged disability after acute lateral ankle ligament disruption has been reported in 20% of patients. With long-term instability, uneven stress distribution with recurrent sprains can lead to osteoarthritis. Various methods for evaluation of the chronically unstable ankle include inversion stress testing, anterior drawer sign, arthrography, and tenography. All of these methods are controversial with false negative results, unreliability, and variations in measurements and interpretation being cited. With this in mind, radiographic instability must be correlated with mechanical and clinical instability. Once all of these findings are correlated the physician can determine the appropriate procedure that will provide the patient with long-term stability. Although more recent studies have addressed repair of chronic instability with ligamentous reinforcement or imbrication, these procedures remain controversial in lieu of Freeman's deafferentiation theory with loss of proprioception. There is also mechanical instability of the subtalar joint, which may also require stabilization. Use of the modified Lee and the Chrisman-Snook techniques as described have provided good results. PMID- 1893337 TI - Common exostectomies of the rearfoot. AB - A review of literature for first metatarsocuneiform joint exostosis, accessory navicular bone, Haglund's syndrome, and os trigonum syndrome does not reveal any significant changes in the process of diagnosis and treatment. The surgical procedures are simple to perform but complications do occur that necessitate the understanding of the pathology and anatomy for each condition. PMID- 1893339 TI - Cole osteotomy. Navicular-cuneiform arthrodesis-transcuboidal osteotomy. PMID- 1893338 TI - Anterior ankle arthroplasty. AB - Osteophytic proliferation at the anterior ankle joint level occurs secondary to repeated direct trauma to the talus and tibia during extreme dorsiflexion of the ankle. This syndrome occurs frequently, especially in athletes. As the exostosis increases in size, ankle joint motion decreases. With increased activity, patients will complain of pain at the anterior aspect of the ankle joint, secondary to the osseous impingement occurring at the tibiotalar joint. If surgical resection is planned, the following should be considered: (1) Proper planning of the incision should give optimal exposure to the tibiotalar joint. (2) Meticulous dissection should be used to identify and carefully retract the superficial and deep neurovascular structures. (3) Adequate repair of the inferior and superior bands of the extensor retinaculum is critical in order to prevent postoperative bowstringing of the anterior tendons. (4) A postoperative course of 3 weeks nonweight bearing is required to help avoid hypertrophic scar formation and allow adequate healing of the extensor retinaculum. (5) Passive range of motion may be started after suture removal at 10 to 14 days. (6) Active range of motion should begin with the initiation of weight bearing at the start of the fourth week. Rewarding results from anterior ankle arthroplasty resection have been seen in those patients presenting with the classical symptoms, as discussed previously, and radiographic evidence of exostosis formation and impingement of the anterior tibiotalar joint. PMID- 1893340 TI - Posterior calcaneal osteotomy. Effect, technique, and indications. AB - Posterior calcaneal osteotomy is a technically simple procedure that may be used to correct frontal, transverse, or sagittal plane displacement of the calcaneus associated with flatfoot deformity. In selected individuals, subluxation about the oblique axis of the midtarsal joint may be stabilized. Forefoot supinatus may be expected to reduce secondary to the reduction of heel valgus obtained, although with deformity chronicity, adaptive midtarsal joint changes may necessitate medial column stabilization. Posterior calcaneal osteotomy increases rotational stability of the subtalar joint in a supinatory direction. In addition, displacement of the posterior calcaneal fragment effects a dynamic correction force by translocation of the Achilles tendon and its posterior relation to the axis of the subtalar joint. PMID- 1893341 TI - Calcaneal osteotomy for retrocalcaneal exostosis. AB - In cases in which radiographic and clinical criteria warrant surgical management of Haglund's deformity, calcaneal osteotomy should be considered. Although postoperative recuperation is extended with this procedure as compared with simple exostectomy, the long-term results have proved more successful. Because of the relative technical difficulty in performing the procedure, perioperative planning and anatomic considerations are essential. PMID- 1893342 TI - Medial column stabilization. AB - This article presented a brief review of medial column stabilizing procedures. The various types of procedures that have been advocated for different deformities have been discussed. It is important to keep in mind that fusion of any of the medial column joints should not be performed as an isolated procedure in flexible flatfoot deformity. Medial column stabilization is only a component procedure when surgically managing a flexible flatfoot. When choosing procedures to correct a flexible flatfoot, thorough preoperative evaluation is important. It is also important to realize that conservative measures should be exhausted before attempting any type of stabilization of the medial column for flexible flatfoot deformity. Specific criteria for flexible flatfoot surgery should include severe uncontrollable deformity, an inability to wear standard foot gear, and persistent pain and disability despite exhaustive conservative therapy. A medial column stabilization is also an excellent procedure for those patients who have end-stage degenerative joint disease of the medial longitudinal arch. PMID- 1893343 TI - Triple arthrodesis. AB - Triple arthrodesis is a useful operation for the relief of chronic pain and repair of instability and deformity in the rearfoot. Due to the nature of the procedure, preoperative surgical planning is of extreme importance to minimize the incidence of long-term problems associated with rearfoot fusion. Complete intraoperative reduction of the deformity and stable rigid fixation is necessary to avoid complications associated with arthrodesis failure and any long-term problems in neighboring joints, particularly in the ankle joint and joints of the mid- and forefoot. Even with good reduction and fixation, there is still the possibility of nonunion or painful pseudoarthrosis. Gait alterations that may lead to residual pain and degenerative joint disease can also be seen. While these problems can occur, they might not be as symptomatic as the patients' preoperative complaints. The surgeon, however, needs to be aware that these conditions exist and may need to be addressed in the long-term care of the patient. PMID- 1893344 TI - Pantalar arthrodesis. AB - Pantalar arthrodesis creates a sensate prosthesis consisting of the ankle and rearfoot complex. Its primary purpose is to create a plantigrade stable rearfoot and ankle. Special attention must be placed on the technical aspects of this procedure, particularly the positioning of the ankle and subtalar complex. PMID- 1893345 TI - DNA flow cytometric analysis of primary operable breast cancer. Relation of ploidy and S-phase fraction to outcome of patients in NSABP B-04. AB - Between 1971 and 1974, 1665 women with primary operable breast cancer were randomized into a National Surgical Adjuvant Breast and Bowel Project (NSABP) trial (B-04) conducted to evaluate the effectiveness of several different regimens of surgical and radiation therapy. No systemic therapy was given. Cells from archival paraffin-embedded tumor tissue taken from 398 patients were analyzed for ploidy and S-phase fraction (SPF) using flow cytometry. Characteristics and outcome of patients with satisfactory DNA histograms were comparable to those from whom no satisfactory cytometric studies were available. In patients with diploid tumors (43%), the mean SPF was 3.4% +/- 2.3%; in the aneuploid population (57%), the SPF was 7.9% +/- 6.3%. Only 29.9% +/- 17.3% of cells in aneuploid tumors were aneuploid. Diploid tumors were more likely than aneuploid tumors to be of good nuclear grade (P less than 0.001) and smaller size (P equals 0.03). More tumors with high SPF were of poor nuclear grade than were tumors with low SPF (P equals 0.002). No significant difference in 10-year disease-free survival (P equals 0.3) or survival (P equals 0.1) was found between women with diploid or aneuploid tumors. Patients with low SPF tumors had a 13% better disease-free survival (P equals 0.0006) than those with a high SPF and a 14% better survival (P equals 0.007) at 10 years than patients with high SPF tumors. After adjustment for clinical tumor size, the difference in both disease free survival and survival between patients with high and low SPF tumors was only 10% (P equals 0.04 and 0.08, respectively). Although SPF was found to be of independent prognostic significance for disease-free survival and marginal significance for survival, it did not detect patients with such a good prognosis as to preclude their receiving chemotherapy. The overall survival of patients with low SPF was only 53% at 10 years. These findings and those of others indicate that additional studies are necessary before tumor ploidy and SPF can be used to select patients who should or should not receive systemic therapy. PMID- 1893346 TI - Stage I and II subdiaphragmatic Hodgkin's disease. AB - From January 1971 to December 1986, 521 patients with Hodgkin's disease were evaluated and treated at the Yale University School of Medicine or one of its close affiliates. A total of 258 patients had pathologic stage (PS) I or II disease, with 239 patients having Hodgkin's disease above the diaphragm (ADHD) and 19 patients having Hodgkin's disease below the diaphragm (BDHD). A comparison of patients with BDHD versus patients with ADHD showed that patients with BDHD were older (mean age, 42 versus 28 years of age, P = 0.005), were initially seen less often with nodular sclerosis subtype (32% versus 77%, P = 0.00001), and had a higher male: female ratio (2.8 versus 1.2, P = 0.12). Ten patients with BDHD (53%) had positive findings at staging laparotomy (0 of 4 clinical stage [CS] IA patients and 10 of 15 (67%) CS II patients). Radiation therapy alone was the initial treatment of choice for 74% of patients with BDHD versus 94% of the patients with ADHD. There was no statistical difference in the overall survival or relapse-free survival rates for patients with BDHD versus ADHD (10-year survival rates, BDHD = 73% and ADHD = 81%). However, patients with BDHD who initially had intra-abdominal disease had a statistically significant increase in death rate (60%) due to Hodgkin's disease compared with patients with BDHD who initially had only peripheral nodal disease (0%). Treatment recommendations for patients with BDHD should be tailored to the specific clinical presentation of each patient. For most PS IA/IIA patients initially seen with peripheral nodal disease, radiation therapy alone is a successful treatment program. However, combined modality therapy should be the treatment of choice for patients with BDHD initially seen with intra-abdominal disease. PMID- 1893347 TI - Should all patients with node-negative breast cancer receive adjuvant therapy? Identifying additional subsets of low-risk patients who are highly curable by surgery alone. AB - This study, which used combined first-generation prognostic factors (tumor size, histologic differentiation, and age) on 408 patients with axillary node-negative (ANN) breast cancer treated by surgery alone without systemic adjuvant therapy between 1976 and 1987 at the Roswell Park Cancer Institute, discerned four subsets of low-risk patients with a 7-year relapse rate of 6% or better. The first subset consisted of 48 patients (12% of the population) with tumors 1 cm or less in diameter that were well or moderately differentiated. These patients had a disease-free rate (DFR) of 100% (95% confidence interval [CI], 94% to 100%). The second subset consisted of 35 patients (9% of the population) with tumors less than or equal to 1 cm that were poorly differentiated or anaplastic. These patients older than 50 years of age had a DFR of 97% (95% CI, 91% to 100%). The third subset consisted of 36 patients (9% of the population) with tumors 1.1 to 2 cm that were well or moderately differentiated. These patients were older than 50 years of age and had a DFR of 94% (95% CI, 85% to 100%). The fourth subset consisted of 36 patients with ductal carcinoma in situ with microscopic invasion. These patients had a DFR of 100% (95% CI, 87% to 100%). Twenty-two of these patients, not in the other subsets mentioned, comprised 5% of the total population. These patients at low risk of recurrence, who comprise one third of the entire node-negative population, are highly curable by local therapy alone and may be spared the risks and costs of routine adjuvant systemic therapy (AST). Patients with tumors larger than 2 cm (152 patients; 37% of the population) are at high risk of recurrence (26% with a DFR of 74% [95% CI, 64% to 84%]) and should routinely receive systemic adjuvant therapy. Patients with tumors up to 2 cm who are not in the low-risk groups fall in a gray area (recurrence, 15% to 21%; DFR, 79% to 85%). For these groups, combining second-generation prognostic factors such as DNA ploidy, S-phase fraction, or cathepsin D should give the physician additional information to aid in making decisions regarding adjuvant therapy. PMID- 1893348 TI - A comparative trial of LC9018 plus doxorubicin and doxorubicin alone for the treatment of malignant pleural effusion secondary to lung cancer. AB - The efficacy and safety of intrapleural LC9018 (Yakult Co. Ltd., Tokyo, Japan) with or without doxorubicin (Adriamycin; Adria Laboratories, Columbus, OH) were evaluated in a randomized, controlled trial performed in 95 patients with malignant pleural effusions secondary to lung cancer. Seventy-six patients were eligible for the assessment of efficacy. The response rate for treatment with intrapleural doxorubicin plus LC9018 (38 patients) was 73.7%, which was significantly higher than the response rate of 39.5% for the control group treated with doxorubicin alone (38 patients) (P less than 0.01). The LC9018 group also showed a significantly greater improvement in performance status (PS) and symptoms (chest pain, chest discomfort, and anorexia) than the control group (P less than 0.05). A significant prolongation of survival was noticed in the LC9018 group (P less than 0.05). The main side effects of LC9018 were fever and transient hepatic dysfunction, but there were no serious adverse reactions. These results suggest that the intrapleural instillation of LC9018 can be recommended for the treatment of malignant pleural effusions. PMID- 1893349 TI - Resectable gastric carcinoma. An evaluation of preoperative and postoperative chemotherapy. AB - Patients with locoregional gastric carcinoma often die because of the low rates of curative resection and frequent appearance of distant metastases (mainly peritoneal and hepatic). To evaluate the feasibility of preoperative and postoperative chemotherapy, 25 consecutive previously untreated patients with potentially resectable locoregional gastric carcinoma received two preoperative and three postoperative courses of etoposide, 5-fluorouracil, and cisplatin (EFP). Ninety-eight courses (median, five courses; range, two to five courses) were administered. Six patients had major responses to EFP. Eighteen patients (72%) had curative resections, and three specimens (12%) contained only microscopic carcinoma. At a median follow-up of 25 months, the median survival of 25 patients was 15 months (range, 4 to 32+ months). Peritoneal carcinomatosis was the most common indication of failure. One patient died of postoperative complications, but there were no deaths due to chemotherapy. EFP-induced toxic reactions were moderate. Preoperative and postoperative chemotherapy for locoregional gastric carcinoma is feasible, and additional studies to develop regimens that could result in 5% to 10% complete pathologic responses may be warranted. PMID- 1893350 TI - Adjuvant whole-abdominal radiation therapy in uterine papillary serous carcinoma. AB - Nine patients from 34 to 74 years of age (median, 67 years of age) with uterine papillary serous carcinoma (UPSC) were treated with whole-abdominal radiation therapy (WART) on an adjuvant basis after cytoreductive surgery. All patients were treated with megavoltage photons to an abdominopelvic field to a median dose of 2500 cGy, with continued treatment to a whole pelvic field to a median dose of 4500 cGy. Three patients received additional boost to the vaginal apex. Follow-up time ranged from 6 to 31 months (median, 25 months) after completion of WART. Six patients had recurrent disease at 5 to 20 months (median, 7.5 months). Four of these patients died of their disease during the follow-up period. Three of six patients in whom treatment failed had disease at the vaginal apex. None of these patients received boost radiation therapy to that site. In contrast, two of three patients remaining disease free were treated with additional vaginal apex irradiation. Based on these results, the authors do not routinely recommend WART for adjuvant treatment of UPSC. They do, however, recommend vaginal apex irradiation for these patients. PMID- 1893351 TI - Recombinant human interleukin-1 beta analogue as a regulator of hematopoiesis in patients receiving chemotherapy for urogenital cancers. AB - Ten patients with advanced urologic cancers who were scheduled to receive at least two courses of chemotherapy were enrolled in this trial. Fifty thousand units of recombinant human interleukin-1 (IL-1) beta analogue OCT-43 (Otsuka Pharmaceutical Co., Ltd., Tokyo, Japan) was administered subcutaneously only once or twice when severe neutropenia (less than 500/microliters) continued for 2 consecutive days. In eight patients, OCT-43 was not injected in the first course of chemotherapy as a control, but was injected in the second course. The durations of leukocytopenia (less than 2000/microliters) and neutropenia (less than 1000/microliters) were significantly shortened in the second course compared with those in the first course in those eight patients. Recovery of neutrophil number from the lowest number was also significantly faster in the second course. Thus, OCT-43 was considered to have hematopoietic activities. However, single or double injection of OCT-43 did not affect the numbers of eosinophilic or basophilic granulocytes, monocytes, or platelets. Adverse effects associated with OCT-43 injections were high fever and chills, but they were controlled by indomethacin. PMID- 1893352 TI - Ewing's sarcoma. Radiographic pattern of healing and bony complications in patients with long-term survival. AB - The radiographic appearance of Ewing's sarcoma was studied retrospectively in 22 patients who survived 5 years or longer after diagnosis and treatment. Expected changes from treatment, including regression of the extraosseous soft tissue mass, periostitis, and reconstitution of the cortex, occurred in all patients. Local recurrence occurred in one patient 10 years after complete remission whereas secondary osteosarcoma occurred more than 5 years after complete remission in two other cases. Both recurrent and secondary tumors presented as new lytic foci at the site of the original primary lesion. Lytic changes from radiation (radiation osteitis) may develop more than 2 years after treatment and in this sample; such findings were widely distributed in the radiation port. The authors conclude that bone remodeling and postradiation changes occur slowly over 2 years after treatment, and that any localized lysis at the primary site is suspicious for recurrence or secondary neoplasm. Knowledge of the expected changes and patterns of local recurrence and secondary neoplasms helps one to detect any significant change in its early phase. PMID- 1893353 TI - Development of systemic lupus erythematosus after interferon therapy for chronic myelogenous leukemia. AB - A 19-year-old man with Philadelphia-positive chronic myelogenous leukemia treated with interferon-alpha (IFN-alpha) therapy for 45 months had systemic lupus erythematosus disease features: malar rash, migratory arthralgias, elevated antinuclear antibodies, elevated antinative DNA, hypocomplementemia, lymphopenia, and proteinuria. After discontinuation of the IFN and initiation of corticosteroids, there was gradual recovery of symptoms, a decline in antinative DNA and antinuclear antibodies to normal levels, and a decrease in proteinuria. The potential association between IFN therapy and the development of systemic lupus erythematosus, and the role of IFN in other autoimmune diseases, is discussed. PMID- 1893354 TI - Colonic ischemia complicating immunotherapy with interleukin-2 and interferon alpha. AB - Colonic ischemia (CI) is a rare complication of high-dose interleukin-2 (IL-2) immunotherapy. This complication occurred in three of 141 patients (2.1%) with metastatic cancer treated with high-dose IL-2 therapy; CI only developed in patients receiving interferon-alpha (IFN) with IL-2 (three of 21, 14%) compared with none of 120 in those patients receiving IL-2 alone (P equals 0.0009). Severe diarrhea (greater than or equal to 7 bowel movements/day) also was significantly more common in patients receiving IFN with IL-2 (six of 21, 29%) than in those receiving IL-2 alone (three of 120, 2.5%, P equals 0.001) and preceded the clinical diagnosis of CI in all three patients. Three of nine patients with severe diarrhea had CI. Hematochezia occurred in four patients, all of whom received IFN with IL-2; three had CI, and the other patient had nonspecific colitis. Differences in vasopressor use did not explain the increased risk of CI in patients receiving IFN; those receiving IFN with IL-2 required phenylephrine less often than patients receiving IL-2 alone (P equals 0.01). The administration of lymphokine-activated killer (LAK) cells had no significant effect on the incidence of CI, severe diarrhea, peritonitis, or vasopressor use; two of three patients with CI, however, had their ischemic episode within 24 hours after the last of three LAK cell infusions. In conclusion, CI is an unusual complication of high-dose IL-2 and IFN immunotherapy. In patients receiving such combination therapy, severe diarrhea is a risk factor for the subsequent occurrence of CI. PMID- 1893355 TI - Basaloid squamous carcinoma of the hypopharynx and larynx associated with second primary tumors. AB - Basaloid squamous carcinoma is believed to be a histologically distinct variant of squamous cell carcinoma of the neck region with 11 cases reported. Two cases arising in the pyriform fossa and vallecula are reported, both of which were associated with second primary malignant tumors: esophageal small cell carcinoma and palatal squamous cell carcinoma, respectively. The authors suggest that basaloid squamous carcinoma may be associated with a high incidence of second primary tumors in the upper gastrointestinal tract or larynx. PMID- 1893356 TI - Soft tissue sarcoma of the pleural cavity. AB - Seventeen cases of soft tissue sarcoma (STS) developing in the pleural cavity were collected from Japanese hospitals, and their clinical and pathologic findings summarized. Eight of the 17 patients had a 15-year to 50-year (mean, 28.8) history of chronic pleural inflammatory disease (pleuritis, pyothorax, and pulmonary tuberculosis) before the onset of the pleural sarcoma. Histologically, malignant fibrous histiocytoma was the most common tumor type (11 cases), followed by angiosarcoma (four). The age at diagnosis of the sarcoma ranged from 15 to 74 years (mean, 58); the male-to-female ratio was 3.3:1. In the eight cases of sarcoma associated with chronic pleural inflammatory disease, male preponderance was more marked (7:1). The commonest presenting symptom was chest pain. A mass could be detected by chest roentgenograms in 13 patients and computed tomographic scans in 15 patients. No patient had distant metastases at first admission. Thirteen patients were treated by surgery, chemotherapy, and/or radiation therapy. Thirteen of the 17 patients died 1 to 87 months (mean, 14.2) after therapy for STS. The actuarial 1-year survival rate was 38.5%. These findings suggest that long-standing pleural inflammation might be an etiologic factor for development of pleural STS. PMID- 1893357 TI - The Istituto Rizzoli-Beretta experience with osteosarcoma of the jaw. AB - Twenty-eight osteosarcomas (OS) of the jaw were reported. There were 15 male and 13 female patients (age range, 9 to 68 years; mean, 36.9 years); 57.1% of the patients were older than 30 years of age. Swelling was the most frequent symptom; it was reported on an average of 6 months before diagnosis. Most of the tumors of the maxilla (eight patients) occurred in the alveolar ridge (six of eight). In the mandible (20 patients), the body was the preferred site (11 of 20). Radiographically most of the lesions were either lytic and sclerotic or only lytic. Histologically, 12 cases (42.9%) were osteoblastic osteosarcoma, ten (35.8%) were chondroblastic, four (14.3%) were fibroblastic, and two (7%) were round cell OS. Of the 28 cases, three (10.7%) were low grade, and 25 (89.3%) were high grade. Thirteen patients had intralesional surgery, and 13 had marginal surgery as their initial treatment. Recurrence was the rule in the first group, and it was 69% in the second group. Twenty patients (71%) died, and eight are alive. Of these, two are alive with disease. In the six patients who are alive and disease-free, all but one had marginal to wide surgical margins at the time of the first procedure or wide margins at the time of the recurrences along with chemotherapy or radiation therapy. In the patient in which the surgical margins were marginal, the lesion was small 2.5 X 2 cm. This patient was alive without evidence of disease after 9 years of follow-up. PMID- 1893358 TI - Comparison of S-phase fraction, working formulation, and Kiel classification in non-Hodgkin's lymphoma. AB - The prognostic value of S-phase fraction (SPF), determined by flow cytometric study from paraffin-embedded tissue, and grading by Working Formulation (WF) and Kiel classification were compared among 245 patients with non-Hodgkin's lymphoma followed for the median of 89 months or until death. Histologic reclassification and SPF determinations were done without knowledge on clinical data. SPF (P equals 0.0001), WF (P equals 0.0003), and Kiel classification (P equals 0.0008) were associated with mortality in lymphoma in a univariate analysis, and WF and SPF were independent prognostic factors in Cox's multivariate analysis. Although SPF correlated strongly both with WF and Kiel grades (P less than 0.0001), low grade and high-grade malignant lymphomas according to Kiel classification, and high-grade lymphomas according to WF could be divided into groups with significantly different outcome by SPF. The results suggests a role for SPF in therapeutic decision-making. PMID- 1893359 TI - The change in patterns of relapse in medulloblastoma. AB - The authors reviewed 89 patients treated for cerebellar medulloblastoma between 1970 and 1989 to determine the impact of changing treatment (high-dose posterior fossa radiation therapy and chemotherapy) on the pattern of failure in medulloblastoma. Between 1970 and 1983, 50 patients (median follow-up, 110 months) were treated with surgery and postoperative craniospinal irradiation (CSI). Nineteen of the 50 (38%) recurred in the central nervous system (CNS). Isolated systemic (bone) metastases occurred in six. The median time to the development of bone metastases was 12 months. Since 1984, 39 patients (median follow-up, 27 months) were treated with preradiation chemotherapy consisting of cisplatin and vincristine for 9 weeks before initiation of CSI. Nine of the 39 (23%) patients recurred in the CNS. There were no systemic failures in this cohort. The actuarial 5-year disease-free survival was 55 +/- 7% for the earlier cohort and 72 +/- 8% for the later cohort (P equals 0.3). Posterior fossa recurrence was associated with radiation therapy to this area. The cumulative incidence of posterior fossa relapse was 50 +/- 13% in patients who received less than 5300 cGy and 18 +/- 7% in those who received 5300 cGy or more (P equals 0.005). All six bone relapses were in patients treated with CSI alone and 5300 cGy or more to the posterior fossa for a 5-year cumulative incidence of bone metastases of 18 +/- 7% compared with 0% for patients treated with 5300 cGy or more and chemotherapy (P equals 0.03). The authors concluded that high-dose radiation therapy has altered the pattern of relapse with an increase in systemic recurrence after radiation therapy alone that is now equivalent to the risk of recurrence in the posterior fossa. Chemotherapy may be indicated in an attempt to decrease this high risk of systemic metastases. PMID- 1893360 TI - Prolactin-producing pituitary carcinoma with pulmonary metastases. AB - Pituitary adenomas rarely are metastatic. Extracranial visceral metastases of prolactinomas were not previously reported. The authors report a case of a 34 year-old man with a prolactin-producing pituitary carcinoma and histologically proven lung metastases. Pathologic examination of the pulmonary spread included electron microscopy and immunohistochemistry; these confirmed prolactin production by the tumor. The patient's presentation at initial diagnosis, disease recurrence, clinical course, management, and response to therapy (with its theoretic basis) are detailed. Despite the use of dopamine analogues (to tolerance and in combination), there was documented intracranial and extracranial disease progression. Possible future therapeutic maneuvers are discussed. PMID- 1893361 TI - Detection of field change in oral cancer using oral exfoliative cytologic study. AB - Four smears were taken from the normal buccal mucosa of 55 oral cancer patients and 76 cancer-free patients. In each case, two were stained by the Papanicolaou method and two underwent Feulgen hydrolysis. Quantitative assessment of nuclear area (NA) and cytoplasmic area (CA) of the Papanicolaou smears was undertaken using a semiautomatic image analysis system. DNA profiles were assessed from the Feulgen smears using a Vickers M85 microdensitometer (Vickers Instruments, York, England) and were found to be diploid for all patients. Results were then analyzed with respect to those patients who took alcohol, tobacco, combination of alcohol and tobacco, and those who took neither. A significant reduction in CA for the oral cancer group (P equals 0.001) but no change in NA (P equals 0.74) was observed. A detailed analysis of alcohol and tobacco habits could identify no significant role for these two factors, in the reduction in cytoplasmic area. Such field change may prove to be of value in predicting the development of second malignant tumors. PMID- 1893362 TI - Mesenteric infarction secondary to tumor emboli from primary aortic sarcoma. Guidelines for diagnosis and management. AB - Primary aortic tumors are rare, difficult to diagnose, and often fatal. This case and a review of the literature identified aortic tumors as a potential source of emboli leading to acute mesenteric insufficiency. The case showed the efficacy of magnetic resonance imaging in diagnosing and determining the extent and location of an aortic tumor. PMID- 1893363 TI - Vaginal adenosis and clear cell carcinoma after 5-fluorouracil treatment for condylomas. AB - Vaginal adenosis and clear cell adenocarcinoma of the vagina occurred in a 44 year-old woman after treatment for condylomata acuminata. She had no known exposure to diethylstilbestrol (DES) in utero. Biopsy-proven vaginal adenosis appeared 8 months after intravaginal 5-fluorouracil application for recurrent urogenital condylomata acuminata. Forty months later, biopsies showed residual adenosis with foci of clear cell adenocarcinoma. Although clear cell adenocarcinoma is associated with vaginal adenosis and cervical ectropion in DES exposed women, its occurrence in adenosis after 5-fluorouracil therapy has not been reported to the authors' knowledge. In this report, this rare but serious complication of treatment of condylomata acuminata is highlighted, and the literature regarding the development of non-DES-associated vaginal adenosis is discussed. PMID- 1893364 TI - Conservative management of anal leiomyosarcoma. AB - Leiomyosarcomas of the large intestine are unusual neoplasms, comprising less than 0.1% of all malignancies of the colon and rectum. Six cases of leiomyosarcoma of the anus have been reported. The optimal treatment for this neoplasm is not known. The standard surgical approach is abdominoperineal resection. The authors report the seventh case of this rare neoplasm and outline its treatment using local excision and iridium 192 brachytherapy in an attempt to preserve the anal sphincter. In selected patients, conservative surgery followed by radiation therapy may be an alternative to radical surgery, with the goals of local control of the disease and anal sphincter preservation. However, more experience is needed before this approach could be recommended routinely. PMID- 1893365 TI - Cholecystectomy as a risk factor for colorectal adenomatous polyps and carcinoma. AB - Multiple studies have suggested a possible relationship between prior cholecystectomy and the occurrence of subsequent colorectal carcinoma. This relationship has been particularly noticed among female patients and for right sided lesions of the colon. In the current study, the authors undertook a case control study among patients who underwent colonoscopy in three private practices in New York City between April 1986 and March 1988. Over this period, 302 adenomatous polyp cases, 106 colon cancer cases, and 507 controls were interviewed regarding their prior history of cholecystectomy. Overall, no significant association was observed between cholecystectomy and either colorectal adenomatous polyps or cancer. Cholecystectomy does not appear to be a significant risk factor for colorectal neoplasia. PMID- 1893366 TI - Later recurrence and longer survival among obese patients with renal cell carcinoma. AB - To investigate the effect of obesity at diagnosis on prognosis of renal cell carcinoma, 360 renal cell carcinoma patients newly diagnosed at 29 hospitals in Oklahoma between January 1, 1981 and December 31, 1984 were followed through December 31, 1987. The Cox proportional-hazard model was used to estimate the hazard ratio, adjusting for other potentially prognostic factors. Both the disease-free interval and the overall survival were longer in patients who were obese (greater than or equal to 120% standard body mass index) at diagnosis. The adjusted-hazard ratio for disease recurrence between obese and nonobese patients was 0.43 (95% confidence interval [CI], 0.19 to 0.98). The obese patients had an adjusted death hazard rate 0.68 times that of the nonobese patients (95% CI, 0.38 to 1.22). Although obesity was reported to increase the risk for renal cell carcinoma, prognosis was no worse and may be better among obese patients with the disease. PMID- 1893367 TI - Endometrial carcinoma in the cancer family syndrome. AB - The study group consisted of 26 women with endometrial adenocarcinoma belonging to 19 cancer families. Age at the onset of cancer, the stage and histologic differentiation of the tumor, initial symptoms, other malignancies, 5-year survival, and transmission of cancer to descendants were studied. The focus was on the importance of endometrial carcinoma in the tumor spectrum. The diagnosis of cancer family was delayed in 14 of the 19 families because endometrial carcinoma was not included in the primary diagnostic carcinoma. This delay may have been harmful to 16 family members who had carcinomas later in life. In ten of the 14 women with multiple malignancies, endometrial adenocarcinoma was the primary malignancy diagnosed, thus enabling the suspicion of a gene carrier and screening for subsequent malignancies. The authors concluded that endometrial carcinoma is a significant component of cancer family syndrome and should be included in the main criteria of Lynch syndrome II. PMID- 1893368 TI - Knowledge and beliefs about cancer in a socioeconomically disadvantaged population. AB - Americans living in poverty experience a higher incidence of and greater mortality from cancer than the nonpoor. At least 50% of the difference in mortality is believed to be due to delay in diagnosis, although risk-promoting lifestyles and behaviors also contribute to decreased survival. A potential exacerbating factor among the poor is inadequate information and knowledge about cancer and its treatment. Interviews were conducted with 128 cancer patients from a socioeconomically disadvantaged population to assess knowledge of cancer and its treatment and to evaluate care-seeking behaviors. Results indicated that although patients relied primarily on their physicians for information about their disease and treatment, a number of misconceptions regarding cancer existed in this population. Notably, nearly 50% of the patients surveyed either denied or did not know that smoking was related to the development of cancer. Additionally, patients frequently reported inappropriate care-seeking behaviors when asked to respond to a series of common disease-related signs or symptoms. These findings suggest that misinformation and misconceptions regarding cancer and its treatment among patients in this sample may contribute to inappropriate care-seeking behaviors. PMID- 1893369 TI - Acquired immunodeficiency syndrome and non-Hodgkin's lymphomas. PMID- 1893370 TI - An analysis of monoclonal antibody distribution in microscopic tumor nodules: consequences of a "binding site barrier". AB - Rational in vivo application of monoclonal antibodies for diagnosis and therapy of cancer requires an understanding of both the global and microscopic pharmacology of macromolecular ligands. Here, we introduce a new mathematical model for antibody distribution into small, prevascular, densely packed nodules (representing either primary or metastatic tumor). For the analysis, we link together several aspects of antibody pharmacology: the global (whole body) pharmacokinetics; transcapillary transport into normal tissue interstitium surrounding the nodule; diffusion into the nodule; nonspecific binding and/or partitioning; specific binding to tumor antigen; metabolism; and lymphatic outflow from the tissue space. Input parameter values are estimated from experimental studies in vitro, in animals, and in clinical trials. Our aim is to explore the sensitivity of antibody localization to variation in three of the important parameters of this model: the rate of transcapillary transport; the rate of lymphatic outflow; and the antigen density. Predictions based on this analysis include the following: (a) High rates of transcapillary transport influx or low rates of lymphatic efflux will enhance antibody percolation into the tumor nodule at early times after injection and increase the average antibody concentration in the tumor at all times; (b) Changes in antibody influx rate will affect the antibody distribution in the tumor at earlier times than do changes in the efflux rate; (c) Reducing the antigen concentration will increase the uniformity of antibody penetration but lower the average concentration in the tumor at all times after injection; and (d) Counter to intuition, lowering the antigen concentration can increase the peak concentrations achieved toward the center of the nodule. If, in addition, there is any metabolism of bound antibody, the concentration-time integral (i.e., the "area under the curve") for the center of the nodule will also be increased by decreasing the antigen concentration. These predictions directly reflect the "binding site barrier" hypothesis of Weinstein et al. (Ann. NY Acad. Sci., 507: 199-210, 1987) and Fujimori et al. (Cancer Res., 49:5656-5663, 1989; J. Nucl. Med., 31:1191-1198, 1990). In general, and perhaps surprisingly until one considers the problem carefully, the parameters governing antibody percolation can have opposite effects on the uniformity of antibody distribution at early and late times. These calculations, using the PERC program set, were done for antibodies, but we believe that the "binding site barrier" will also prove important for other injected macromolecules, for at least some highly bindable injected small molecules, for lymphokines and cytokines released from transfected cells injected in vivo, and, indeed, for endogenous species such as the autocrine-paracrine factors. PMID- 1893371 TI - A case-control study of serum folate levels and invasive cervical cancer. AB - Although small intervention trials have suggested that folate supplementation reduces cervical dysplasia, the association of blood folate concentrations with invasive cervical cancer risk has not been investigated in well-controlled epidemiological studies. A study was conducted with newly diagnosed Stage I and II invasive cervical cancer cases and controls in 4 Latin American countries. Ninety-five% of subjects donated blood samples, resulting in 330 case and 565 control serum samples analyzed for folate concentrations by radioassay. Cases did not differ significantly from controls in mean levels of folate (5.00 and 4.90 ng/ml, respectively). No associations were observed between quartiles of serum folate and risk of cervical cancer after adjustment for other risk factors, and no interactions with established risk factors were observed. Folate levels were also unrelated to risk among women who might have compromised folate status because of recent or extended oral contraceptive usage or multiple pregnancies. Further, mean levels of folate were similar by stage of disease, arguing against an effect of disease progression on serum values. These results do not support a role for serum folate in the etiology of invasive cervical cancer. PMID- 1893372 TI - Metabolic activation of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone as measured by DNA alkylation in vitro and its inhibition by isothiocyanates. AB - The bioactivation of the tobacco-specific nitrosamine, 4-(methylnitrosamino)-1-(3 pyridyl)-1-butanone (NNK), by microsomes from target organs was studied with an in vitro microsome-mediated DNA alkylation system. Mouse lung, rat lung, and rat nasal microsomes catalyzed a time- and protein-dependent DNA methylation by [methyl-3H]NNK with activities of 4.11, 0.95, and 137.4 pmol/mg DNA/mg protein/h, respectively. The DNA methylation of NNK catalyzed by all three microsomal systems was inhibited by cytochrome P-450 inhibitors, such as carbon monoxide and metyrapone, but not by the cyclooxygenase inhibitor, aspirin, or by prolonged preincubation in the absence of NADPH. The possible involvement of specific P450 isozymes was assessed by specific inhibitory antibodies. An anti-P450IIB1&2 antibody significantly inhibited the DNA methylation by 45 and 32% in mouse lung and rat lung, respectively, whereas anti-P450IA1 and anti-P450IIE1 antibodies failed to show significant inhibition. All antibodies showed no inhibition in rat nasal microsomes. Glutathione inhibited the DNA methylation in a concentration dependent manner in all three microsomal systems. Phenethyl isothiocyanate (PEITC), at doses of 0.25 and 1.00 mmol/kg body weight, was given intragastrically 2 h before sacrifice to mice and 24 h before sacrifice to rats, respectively; both mouse and rat lung microsomal activities were inhibited by about 40 and 90% by the low- and high-dose PEITC treatments, respectively. The rat nasal microsomes were only inhibited by the high-dose PEITC treatment by about 40%. PEITC, 4-phenylbutyl isothiocyanate, and 6-phenylhexyl isothiocyanate all inhibited the microsome-mediated DNA methylation of NNK in vitro, with 4 phenylbutyl isothiocyanate and 6-phenylhexyl isothiocyanate being more potent than PEITC and the mouse lung microsomes more sensitive than the rat lung and nasal microsomes. All three microsomal systems were shown to catalyze the in vitro DNA pyridyloxobutylation by [5-3H]NNK. On an equal protein basis, the rat nasal microsomes were much more active in catalyzing the DNA pyridyloxobutylation. PMID- 1893373 TI - Antipain-induced suppression of oncogene expression in H-ras-transformed NIH3T3 cells. AB - Antipain (AP; 50 micrograms/ml) inhibits transformation of NIH3T3 cells after transfection with an activated H-ras oncogene. To determine whether AP effects on transformation are associated with alterations in oncogene expression, NIH3T3 cells were cotransfected with an activated H-ras oncogene and the selectable marker gene aph, and gene expression was quantified. Fifty percent of geneticin resistant colonies which were exposed to AP failed to express the transformed phenotype as determined by their inability to grow in soft agar. Northern blot analysis of the transformed and nontransformed colonies revealed that suppression of H-ras transformation by AP was associated with a decrease in expression of the exogenously transfected H-ras gene by approximately 4-fold. Expression of the endogenous oncogene c-myc was decreased by approximately 2.5-fold, to levels seen in untransfected cells. AP-treated colonies that retained the transformed phenotype had levels of oncogene expression that were similar to untreated ras transformed colonies. Southern blot analysis revealed no effects of AP on incorporation or copy number of the H-ras gene. PMID- 1893374 TI - Integrated microscopic-macroscopic pharmacology of monoclonal antibody radioconjugates: the radiation dose distribution. AB - Accurate dosimetry is essential for the assessment of radioimmunotherapy. Most often studied to date has been the macroscopic dosimetry related to organ and tumor distribution of the radiolabeled antibody, but the question of microscopic dose heterogeneity is also important. To address the latter issue, we have taken an integrated approach to the pharmacology, taking into account whole-body distribution, transcapillary transport, percolation through the tumor interstitial space, antigen-antibody interaction, and antibody metabolism. The first step is to simulate the spatial antibody concentration profile in a tumor as a function of time after i.v. (e.g., bolus) injection, using reasonable values for the parameters involved. The second step is to calculate, also as a function of time, the absorbed radiation dose distribution resulting from each concentration profile. Parameter values for IgG pharmacology and a radiation point source function for 131I are used to explore the effect of antibody distribution profiles on absorbed dose in the tumor. The geometry simulated corresponds to a spherical nodule of densely packed tumor cells. Absorbed doses are calculated for radiation from a single nodule (e.g., a micrometastasis or prevascular primary tumor) and for a cubic lattice of such nodules (e.g., corresponding to nodular lymphoma). As noted in our previous studies, there is a "binding site barrier." Binding to antigen retards antibody percolation into the nodules; high antibody affinity tends to decrease percolation and give a higher absorbed dose near the surface of each nodule. Heterogeneous antibody distribution results in a heterogeneous absorbed dose. This is more apparent in the case of radiation from a single nodule than it is for radiation from within an array of nodules. Dehalogenation results in a lower absorbed dose over time, and the effect is more apparent at later times after injection. PERC-RAD, the computer program package developed for these analyses, provides a convenient and flexible way to assess the impact of macroscopic and microscopic parameters on the distribution of radioimmunoconjugates and on the consequent profile of absorbed radiation dose in tumors. This mathematical model and the general principles developed here can be applied as well to other radiolabeled biological ligands. PMID- 1893375 TI - The effects of transforming growth factor beta 3 on the growth of highly enriched hematopoietic progenitor cells derived from normal human bone marrow and peripheral blood. AB - The effects of transforming growth factor beta 3 (TGF-beta 3) on growth in semisolid cultures of enriched hematopoietic progenitors derived from normal human marrow and blood were evaluated. Conditioned media from the Mo-T cell line (MoCM) were the source of colony-stimulating factors used to optimally stimulate primitive progenitors. To assess whether a proportion of granulocyte/monocyte (GM) progenitors were prevented from cycling, all sizes of GM aggregates were evaluated from 3 to 20 days. The activity of TGF-beta 3 on the growth of erythroid burst-forming units (BFU-E) and granulocyte-macrophage colony-forming units (CFU-GM) was similar to that observed for TGF-beta 1. TGF-beta 3 (10, 100, and 1,000 pmol/liter), added initially or 72 h after initiation of culture, did not significantly affect the total number of marrow GM aggregates at 3, 7, 14, and 20 days, but TGF-beta 3 (1,000 pmol/liter), added initially, reduced the total number of blood GM aggregates. This suggests that some blood GM progenitors might be blocked from cycling but that the great majority of marrow GM progenitors are not blocked. Whether TGF-beta 3 (10, 100, and 1,000 pmol/liter) was added initially or after 72 h of stimulation by MoCM, there was a dose dependent reduction of marrow and blood GM colony size even when the total number of colonies was unaffected. TGF-beta 3 (10, 100, and 1,000 pmol/liter), added initially or at 72 h, reduced in a dose-dependent manner the size of marrow and blood-derived BFU-E. TGF-beta 3 (1,000 pmol/liter) was more likely to reduce the total number of marrow and blood BFU-E, and this increased sensitivity of the erythroid lineage may prevent the development of this population in colonies derived from multipotential colony-forming unit-granulocyte/erythroid/monocyte (CFU-GEM). The results suggest that the main effect of TGF-beta 3 and TGF-beta 1 is to slow the rate of proliferation of hematopoietic progenitors rather than to prevent them from beginning proliferation. This results in a reduction in colony size which prevents the identification of primitive versus mature progenitor on the basis of standard criteria of colony size. PMID- 1893376 TI - Distribution of tamoxifen and its metabolites in rat and human tissues during steady-state treatment. AB - A procedure for the extraction of tamoxifen and metabolites from various rat and human tissues was developed and verified. With this method, we determined the drug and metabolite concentrations during one dosing interval in various tissues (brain, fat, liver, heart, lung, kidney, uterus, and testes) of rats given tamoxifen once daily for 3 or 14 days, and in various normal and malignant tissues obtained during surgery or at autopsy from patients with breast cancer treated with tamoxifen. In the rat, the concentrations of tamoxifen and metabolites in most tissues were 8- to 70-fold higher than in serum. The highest levels were observed in lung and liver; substantial amounts were also recovered from kidney and fat. Fluctuations of metabolites and tamoxifen content in most tissues were observed during one dosing interval, corresponding to a ratio of 4:8 between Cmax and Cmin, except in fat and testicular tissues, where the drug concentrations were relatively stable. In addition to tamoxifen, N desmethyltamoxifen, followed by 4-hydroxytamoxifen, 4-hydroxy-N desmethyltamoxifen, and N-desdimethyltamoxifen, were abundant in most tissues. In contrast, adipose tissue contained only small amounts of these metabolites. The concentrations of tamoxifen and metabolites found in human normal and malignant tissues confirmed and extended the conclusions made in the experiments with rats. In humans, levels were 10- to 60-fold higher in tissues than in serum, and relatively high concentrations were detected in liver and lung. Additionally, pancreas, pancreatic tumor, and brain metastases from breast cancer and primary breast cancer retained large amounts of drug. Again, the amounts of demethylated and hydroxylated metabolites were high in most tissues, except in fat. Tamoxifen and some metabolites were also present in specimens of skin and bone tissue. In one patient, significant amounts of drugs could be detected in lung, heart, ovary, and intestinal wall 14 months after withdrawal of tamoxifen, demonstrating efficient retention and slow washout of these compounds in human tissue. PMID- 1893377 TI - Pharmacology and phase I trial of high-dose oral leucovorin plus 5-fluorouracil in children with refractory cancer: a report from the Children's Cancer Study Group. AB - Because of the synergy seen in adult trials when 5-fluorouracil is combined with leucovorin, we initiated a Phase I trial of this combination in children's refractory cancer. Leucovorin, an equal mixture of the (6R,S)-diastereoisomers, was administered p.o. for 6 consecutive days as 4 equal doses at 0, 1, 2, and 3 h totaling 500 mg/m2/day. 5-Fluorouracil was given daily on days 2 to 6 as an i.v. bolus immediately following the last dose of leucovorin. The leucovorin dose was held constant while the 5-fluorouracil dose was escalated in cohorts of patients from 300 mg/m2/day to its maximally tolerated dose. Thirty-five patients (19 with acute leukemia and 16 with solid tumors) were evaluable for toxicity. The maximally tolerated dose of FUra was 450 mg/m2/day for 5 treatments for patients with solid tumors and 650 mg/m2/day for 5 treatments for the children with leukemia. The dose-limiting toxicities were myelosuppression and stomatitis. Other side effects included transient, mild elevations of serum transaminases, mild nausea, vomiting, and diarrhea. The pharmacokinetics of high-dose p.o. leucovorin was studied in 23 children. There was considerable interpatient variability in the plasma concentrations of total bioactive folates (TBAF), (6S) leucovorin, and (6S)-5-methyltetrahydrofolic acid. The maximum plasma concentration (Cmax) of TBAF was 821 +/- 97 (SE) nM, occurring at a median of 8 h; the Cmax of (6S)-leucovorin was 77 +/- 11 nM, occurring at 4 h. The TBAF concentration fell to 146 +/- 42 nM by 24 h. (6S)-5-Methyltetrahydrofolic acid accounted for 90 +/- 7% of the TBAF at the Cmax. The plasma concentration of (6R) leucovorin, the unnatural isomer, was equal to that of TBAF. Thus, p.o. leucovorin reduced the 5-fold excess of (6R)-leucovorin over TBAF seen after i.v. doses. The relative amounts of the three major plasma species were approximately the same as in adults, even though the Cmax of each compound was lower. PMID- 1893378 TI - All-trans-retinoic acid inhibits the growth of human rhabdomyosarcoma cell lines. AB - We have been evaluating the role of all-trans-retinoic acid (RA) in the differentiation and growth of human rhabdomyosarcoma (RMS) cell lines. Treatment of both embryonal (RD) and alveolar (RH30) human RMS cell lines with all-trans-RA resulted in a dose-dependent inhibition of cell growth with a maximal inhibition of 92 and 66%, respectively, at 5 x 10(-6) M. When 13-cis-RA was used under identical experimental conditions, maximal growth inhibition was 41 and 37%, respectively. This stereo-specific growth inhibition was not associated with morphological or biochemical evidence of myogenic differentiation. Furthermore, all-trans-RA demonstrated no evidence of competition with binding of insulin-like growth factor II (IGF-II), an autocrine growth factor in RMS, to its membrane receptor as evaluated by an [125I]IGF-I-receptor-binding assay. Attempts to rescue all-trans-RA growth-inhibited RMS cells with exogenous IGF-II resulted in no increase in growth compared to cells treated with all-trans-RA alone. We conclude that RA inhibits the growth of human RMS cell lines in a dose-dependent, stereo-specific manner, is not associated with differentiation, and does not appear to be directly related to IGF-II. PMID- 1893379 TI - Antitumor activity of UCN-01, a selective inhibitor of protein kinase C, in murine and human tumor models. AB - Antitumor activity of UCN-01 (7-hydroxy staurosporine), a selective inhibitor of Ca2+- and phospholipid-dependent protein kinase C, was examined in comparison with staurosporine, a nonselective inhibitor of protein kinases, on human and murine tumor cell lines which have some aberrations in cellular signal transduction. UCN-01 inhibited the growth of five tumor cell lines about 9 to 90 times less potently than staurosporine in vitro. UCN-01 showed an in vivo antitumor effect against three human tumor xenografts [epidermoid carcinoma A431 (c-erbB-1 overexpression), fibrosarcoma HT1080 (N-ras activation), and acute myeloid leukemia HL-60 (N-ras activation)], giving a minimum treated/control ratio of 0.40 (P less than 0.01), 0.17 (P less than 0.01), and 0.61 (P less than 0.05), respectively. UCN-01 also exhibited significant antitumor activity against two murine tumor models (fibrosarcoma, K-BALB and M-MSV-BALB), which activated the v-ras and v-mos oncogenes, showing a minimum treated/control ratio of 0.27 (P less than 0.01) and 0.21 (P less than 0.01). Staurosporine did not show significant antitumor activity against any of these five tumors. UCN-01 inhibited the down-modulation of epidermal growth factor receptor caused by phorbol 12 myristate 13-acetate in A431 cells at a near 50% inhibitory concentration for cell growth. These results imply that UCN-01 is a promising antitumor agent which has a novel mechanism(s) of action. PMID- 1893380 TI - Reversal of adriamycin resistance by recombinant alpha-interferon in multidrug resistant human colon carcinoma LoVo-doxorubicin cells. AB - Reversal of the drug resistance phenotype by the use of agents which induce cell differentiation offers an experimental approach to the study of chemoresistance. In numerous in vitro models, alpha-interferon (alpha-IFN) has been shown to induce phenotypical changes and to modulate the growth of cancer cells. The aim of the present study was to define the effect of alpha-IFN on the Adriamycin sensitivity of the human colon adenocarcinoma cell line, LoVo, and its Adriamycin resistant variant, LoVo/DX. Pretreatment of LoVo/DX cells with 500 units/ml of alpha-IFN increased sensitivity to low doses of Adriamycin. Similar treatment conditions did not change the sensitivity of the parental cell line. Following treatment of the LoVo/DX cells with alpha-IFN plus 100 ng/ml Adriamycin for 1 h, 30% of the cells survived compared to 100% of untreated cells. This effect was not related to changes in cell cycle kinetics induced by alpha-IFN treatment and did not result from variations in the expression of P-glycoprotein at the cell surface, as assessed by flow cytometric analysis using monoclonal antibody MRK16. Adriamycin accumulation was increased by alpha-IFN as assessed by spectrofluorometric analysis. Thus, the data suggest that in LoVo/DX cells, alpha IFN increased Adriamycin cytotoxicity through modulation of the multidrug resistance phenotype. PMID- 1893381 TI - Mesenchyme-induced changes in the neoplastic characteristics of the Dunning prostatic adenocarcinoma. AB - To investigate the possibility that mesenchyme can alter the neoplastic properties of an established carcinoma, small (0.5-mm cubes) pieces of the Dunning prostatic adenocarcinoma (DT) were grown in association with seminal vesicle mesenchyme (SVM) for 1 mo. Differentiated DT epithelial cells harvested from the resultant tissue recombinants (1 degree SVM + DT) were recombined with fresh SVM to generate 2 degrees SVM + DT recombinants which were grafted to secondary male hosts. After 3 additional mo of in vivo growth, grafts of (a) 2 degrees SVM + DT recombinants, (b) DT epithelial cells derived from 1 degree SVM + DT recombinants, or (c) DT by itself were examined for growth rate and tumorigenicity. Grafts of DT by itself formed large tumorous masses that completely overgrew the host's kidney, while 2 degrees SVM + DT recombinants and differentiated DT epithelial cells from 1 degree SVM + DT recombinants exhibited only modest growth during a 3-mo period. The loss of tumorigenicity was associated with a striking reduction in [3H]thymidine labeling index in epithelial cells of 2 degrees SVM + DT recombinants. DT grafted by itself maintained its typical histopathological characteristics containing small ducts lined with undifferentiated squamous to cuboidal epithelial cells. Grafts of 2 degrees SVM + DT recombinants contained large ducts lined by epithelial cells exhibiting three different patterns of histodifferentiation: (a) basophilic tall columnar epithelial cells with a clear supranuclear cytoplasm and basally located oval nuclei; (b) a heterogeneous epithelium containing large clear cells with pale cytoplasm interspersed among dark staining tall columnar epithelial cells; and (c) undifferentiated squamous to cuboidal epithelial cells. The first two epithelial types were the predominant cell types. Grafts of differentiated DT epithelial cells derived from 1 degree SVM + DT recombinants formed medium-sized ducts lined with cuboidal to low columnar epithelial cells. These results demonstrate a continued responsiveness of carcinoma cells to mesenchymal inductors which can induce secretory cytodifferentiation and elicit a reduction in growth rate and loss of tumorigenesis. PMID- 1893382 TI - In situ localization of 3.2.3+ natural killer cells in tissues from normal and tumor-bearing rats. AB - A monoclonal antibody, designated 3.2.3, which recognizes a novel Mr 60,000 disulfide-linked lytic triggering structure present on rat large granular lymphocytes and natural killer (NK) cells was recently described (W. H. Chambers et al., J. Exp. Med., 169: 1373-1389, 1989). The present study describes the use of 3.2.3 to identify the in situ tissue distribution of large granular lymphocytes/NK cells in different organs from normal and tumor-bearing F344 rats. Frozen tissue sections were prepared and stained with monoclonal antibody 3.2.3 using an avidinbiotin immunoperoxidase technique. 3.2.3+ NK cells were easily identified using this technique, and quantitative analysis of various tissues of normal rats demonstrated that (a) in the spleen, most NK cells were located, sometimes as aggregates, in the red pulp (12.4% of total nucleated cells in that organ compartment) with relatively few noted in the white pulp (0.2-2.3%); (b) in the liver, 3.2.3+ cells were rare, sparsely distributed, and located primarily in the sinusoids (1.2%); (c) in the lungs, 3.2.3+ cells were located in the interstitium (3.7%); (d) in the thymus, 3.2.3+ cells were found primarily in the medulla (1.8%) adjacent to the cortex but not in the cortex itself (0.2%); (e) in the lymph node, most 3.2.3+ cells were contained in the paracortex (6.9%); and finally (f) in the small bowel, 3.2.3+ cells were present in the lamina propria (8.6%) and as aggregates in the interfollicular zone of Peyer's patches (0.7%). To study the distribution of 3.2.3+ NK cells in developing tumor metastases, we induced liver metastases by intrasplenic injection of MADB106 mammary adenocarcinoma cells and prepared frozen tissue sections of the liver 10-14 days later. We found that the frequency of 3.2.3+ cells in the developing liver metastases was 3-6 times higher than in the surrounding normal liver tissue. Moreover, the frequency of 3.2.3+ NK cells was equivalent to the frequency of tumor-infiltrating CD5+ T-cells identified in the same tumor lesions. This suggests specific infiltration of 3.2.3+ NK cells in early developing metastatic lesions. These results indicate that monoclonal antibody 3.2.3 will be valuable in analyzing the involvement of NK cells in various pathological states. PMID- 1893383 TI - Growth and metastasis of fresh human melanoma tissue in mice with severe combined immunodeficiency. AB - Cryopreserved cell suspensions of freshly excised melanoma metastases from nine patients were injected s.c. into C.B-17 severe combined immunodeficiency (SCID) mice. All 9 tumors grew as s.c. masses and six of nine were successfully transplanted into other SCID mice. Transplant inocula as low as 5 x 10(5) cells resulted in 100% tumor incidence. Moreover, seven of nine tumors metastasized, five from the original s.c. implants and two from transplanted s.c. tumors. Metastases were detected mainly in the lungs but also were found in abdominal viscera (liver, spleen, and pancreas) and thoracic lymph nodes. Flow cytometric analysis showed that expression of a panel of melanoma antigens, melanoma associated proteoglycan, ganglioside GD3, and ganglioside GD2, was maintained with SCID passage. The original tumor inocula contained a variable percentage of tumor-associated lymphocytes (1-76%). Flow cytometry analysis indicated that these were mainly CD3+ T-cells. However, there was no correlation between the percentage of tumor-associated lymphocytes and the time required for development of a palpable tumor after s.c. injection or the ability to metastasize. These results demonstrate the growth and spontaneous metastasis of fresh human melanoma in SCID mice and suggest that this model could be important for therapeutic and basic biological studies. PMID- 1893384 TI - Crocidolite asbestos fibers undergo size-dependent microtubule-mediated transport after endocytosis in vertebrate lung epithelial cells. AB - The large respiratory epithelial cells within primary cultures of newt (Taricha granulosa) lung are uniquely suited for high resolution video-enhanced light microscopic studies. We show here that these cells incorporate crocidolite asbestos fibers within 18 h by endocytosis. Once inside the cell, fibers less than 5 microns in length are seen by video light microscopy to undergo saltatory transport at a maximum velocity of 1.18 microns/s. By contrast, fibers over 5 microns long rarely exhibit saltatory motion. Over time, all of the fibers become preferentially located near the nucleus. This perinuclear accumulation is largely inhibited by disassembling the cytoplasmic microtubules with nocodazole. Same cell correlative light and electron microscopy reveal that fibers exhibiting saltatory behavior are enclosed within a membrane. From these observations we conclude that, upon incorporation into epithelial cells, asbestos fibers undergo size-dependent active transport along cytoplasmic microtubules. Our data are the first to link the dimension-dependent transforming ability of asbestos fibers to a basic cellular function, i.e., the microtubule-dependent transport of cellular components. PMID- 1893385 TI - Growth factor messenger RNA expression by human breast fibroblasts from benign and malignant lesions. AB - Breast tumors are a complex mix of epithelial, stromal, and vascular elements. We examined primary cultures of breast fibroblasts derived from benign and malignant lesions for expression of various growth factors. All fibroblast cultures, regardless of whether they were derived from benign or malignant lesions, expressed platelet-derived growth factor A chain, basic fibroblast growth factor, fibroblast growth factor 5, and transforming growth factor beta 1 mRNA. None expressed platelet-derived growth factor B chain or transforming growth factor alpha mRNA. However, examination of mRNA expression for the insulin-like growth factors revealed that 7 of 8 fibroblasts derived from benign lesions expressed insulin-like growth factor I (IGF-I) mRNA, while only 1 of 9 fibroblasts derived from malignancies expressed IGF-I mRNA. The opposite picture was seen for insulin like growth factor II (IGF-II) mRNA expression, in which 1 of 9 benign-derived fibroblasts expressed IGF-II mRNA, while 5 of 9 malignant-derived fibroblasts expressed IGF-II. This correlated with previous in situ hybridization data, which showed IGF-I mRNA expression confined to the stroma of benign breast tissue. PDGF treatment of tumor fibroblasts resulted in a 3-fold increase in IGF-II mRNA. Thus there was an apparent dichotomy between IGF-I mRNA expression in the majority of fibroblasts derived from benign lesions and IGF-II mRNA expression in the majority of tumor-derived fibroblasts. Since the insulin-like growth factors are potent mitogens for breast tumor epithelial cells, this further supports the notion of a paracrine growth-promoting role for the insulin-like growth factors in breast lesions and suggests that IGF-II may be the more important growth promoter in malignant lesions. PMID- 1893387 TI - A crown and sleeve removable denture with periodontally involved teeth as abutments: an alternative to a conventional complete denture. AB - This case report describes the use of a crown and sleeve coping denture in the treatment of a patient who presented with poor periodontal prognosis of multiple teeth. The prosthesis is designed to splint, stabilize, and retain periodontally involved teeth that are not suitable to support conventional partial dentures. In addition, it offers increased retention and stability. PMID- 1893388 TI - The efficacy and safety of ketoprofen in postsurgical dental pain. AB - Ketoprofen is a nonsteroidal anti-inflammatory drug with both anti-inflammatory and analgesic properties. This paper will review the efficacy and safety of ketoprofen in patients experiencing pain after the surgical removal of impacted third molar teeth. PMID- 1893386 TI - Correlation of chondroitin sulfate proteoglycan expression on proliferating brain capillary endothelial cells with the malignant phenotype of astroglial cells. AB - Human glioblastomas (five of five), the most malignant astroglial-derived tumors, specifically express a chondroitin sulfate proteoglycan that is recognized by monoclonal antibody 9.2.27 and localized to the glioma cell surface, proliferating endothelial cells, and the perivascular extracellular matrix within the tumor bed. In contrast, the expression of this proteoglycan in normal adult neocortex and white matter is limited to the smooth muscle of small arteries, while normal glia, endothelial cells, and endothelial cell basement membranes are nonreactive. Moreover, two anaplastic astrocytomas, representing medium-grade astroglial-derived tumors, fail to react with monoclonal antibody 9.2.27. In culture, glioblastoma and capillary brain endothelial cells specifically synthesize a 250-kDa core protein and a high-molecular-mass chondroitin sulfate proteoglycan, recognized by monoclonal antibody 9.2.27. These data suggest a correlation between the expression of this chondroitin sulfate proteoglycan on proliferating brain capillary endothelial cells and the malignant phenotype of astroglial cells. The prominent perivascular localization of chondroitin sulfate proteoglycan makes it a marker for both proliferating brain capillary endothelial cells and the most malignant transformed astroglial cells, thus providing an ideal target for the immunotherapy of glioblastoma. PMID- 1893389 TI - Bone-fill in guided tissue regeneration of periodontal defects. AB - The feasibility of regeneration and attachment of periodontal ligament and alveolar bone after surgical treatment of periodontal defects is documented in the literature. This article presents four cases of clinical and radiographic evidence showing apparent new attachment after root isolation with expanded polytetrafluoroethylene (PTFE) periodontal material, following the principle of guided tissue regeneration. Combination one-, two-, and three-wall angular bony defects of molars and incisors were exposed and root planed. A skirt of PTFE periodontal material was sutured into place and removed after 6 weeks in situ. Reductions in probed pocket depths and gain in bone-fill, as revealed by radiography, were achieved in every case. Maximum regeneration of alveolar bone was 6 mm in the two-wall angular defect of a first molar; minimum gain in bone height was 3 mm. PMID- 1893390 TI - The significance of needle gauge in dental injections. AB - Dentists administer injections on a routine basis with minimal consideration given to the needle used. Patients often associate pain with injections. Gauge is the measuring standard used in needle width classification. Despite the institution of American National Standards Institute/American Dental Association (ANSI/ADA) specification no. 54, variables still exist in classification of needles. The authors describe inside and outside diameters of the needle, ability to aspirate, and effect of needle size on pain, and offer suggestions for needle selection. PMID- 1893391 TI - Histopathologic appraisal of an oral hemangioma treated with a sclerosing agent. AB - The histopathologic aspect of a case of oral soft tissue hemangioma treated with a sclerosing agent is described. Various modes of treatment for hemangioma are discussed. PMID- 1893392 TI - Assessing legal responsibility for implant failure. AB - The number of malpractice suits related to implants has recently increased significantly, with awards that are among the largest in dentistry. This article discusses the principles involved in assessing liability for implant failure and the various clinical situations that can affect liability in implant practice. The author also provides a list of the interrogatories required of defendants in malpractice suits related to implants. PMID- 1893393 TI - Current bibliography of cell calcium prepared by the University of Sheffield Biomedical Information Service. PMID- 1893394 TI - Spectrofluorimetric and image recordings of spontaneous and lectin-induced cytosolic calcium oscillations in Jurkat T cells. AB - Intracellular variations in Ca2+ concentrations have been measured in single Jurkat T lymphocyte variants (77 6.8 and E6.1) using Fura-2 as a probe. Under basal conditions, the cytosolic Ca2+ level is stable but some cells show spontaneous Ca2+ oscillations (frequency, 0.30 +/- 0.06 Hz). These oscillations are sensitive to the external concentration of Ca2+ since they can no longer be observed when the bathing solution is replaced (superfusion) with a Ca(2+)-free medium or when a Ca2+ chelator (EGTA) is added. Various changes in the cytosolic concentration of Ca2+ ([Ca2+]i) can be observed when the cells are exposed to the mitogenic lectin phytohemagglutinin (PHA, 80 nM). For instance, in the case of non-oscillating cells, the lectin induces either a rapid increase in [Ca2+]i that is followed by a sustained response (plateau) or it triggers Ca2+ spikes. In the case of experiments done in Ca(2+)-free medium, only the initial spike was observed. In the case of spontaneously oscillating cells, PHA induces a rapid increase in [Ca2+]i that is followed by a plateau where oscillations are absent. In every case, the PHA-dependent Ca2+ response is abrogated in a Ca(2+)-free medium. Computer simulations based on the model of Goldbeter et al. [27] show that the various Ca2+ responses of Jurkat cells are related to the cytosolic level of free Ca2+. Video imaging analyses show that the cellular Ca2+ responses are not homogeneous whether the observations are made in spontaneously oscillating Jurkat cells or when they are exposed to PHA. PMID- 1893395 TI - Ca(2+)-dependent and independent mitochondrial damage in hepatocellular injury. AB - The alterations of mitochondrial membrane potential during the development of irreversible cell damage were investigated by measuring rhodamine-123 uptake and distribution in primary cultures as well as in suspensions of rat hepatocytes exposed to different toxic agents. Direct and indirect mechanisms of mitochondrial damage have been identified and a role for Ca2+ in the development of this type of injury by selected compounds was assessed by using extracellular as well as intracellular Ca2+ chelators. In addition, mitochondrial uncoupling by carbonylcyanide-m-chloro-phenylhydrazone (CCCP) resulted in a marked depletion of cellular ATP that was followed by an increase in cytosolic Ca2+ concentration, immediately preceding cell death. These results support the existence of a close relationship linking, in a sort of reverberating circuit, the occurrence of mitochondrial dysfunction and the alterations in cellular Ca2+ homeostasis during hepatocyte injury. PMID- 1893396 TI - Regulation of intracellular calcium homeostasis in Trypanosoma cruzi. Effects of calmidazolium and trifluoperazine. AB - Trypanosoma cruzi epimastigotes maintained an intracellular free calcium concentration of about 0.15 microM, as measured with the fluorescent indicator Fura-2. The maintenance of low [Ca2+]i is energy-dependent since it is disrupted by KCN and FCCP. When the cells were permeabilized with digitonin, the steady state free Ca2+ concentration in the absence of ATP was about 0.7 microM. The additional presence of ATP resulted in a steady-state level close to 0.1-0.2 microM which compares favorably with the concentration detected in intact cells. Intracellular Ca2+ uptake at high levels of free Ca2+ (greater than 1 microM) was due to energy-dependent mitochondrial uptake as indicated by its FCCP sensitivity. However, as the free Ca2+ concentration was lowered from 1 microM, essentially all uptake was due to the ATP-dependent Ca2+ sequestration by the endoplasmic reticulum as indicated by its stimulation by ATP, and its inhibition by sodium vanadate. High concentrations of the calmodulin antagonist trifluoperazine, inhibited both the Ca2+ uptake by the endoplasmic reticulum and by the mitochondria, while calmidazolium released Ca2+ from both compartments. In addition, trifluoperazine and calmidazolium inhibited respiration and collapsed the mitochondrial membrane potential of T. cruzi, thus indicating non-specific effects unrelated to calmodulin. PMID- 1893397 TI - Effects of Fe(3+)-tumor cell interaction on Ca(2+)-uptake by Ehrlich ascites tumor cells. AB - Fe3+ ions complexed by various ligands induce an increased Ca2+ uptake by Ehrlich carcinoma ascites cells that is proportional to the thermodynamic stability constant of the complex, and the greatest increase is observed with ferric lactate. The absence of ATPase inhibition showed by this ferric complex, suggests that an increased passive diffusion of Ca2+ due to structural modifications of the cell membrane is the most probable cause of this phenomenon. PMID- 1893398 TI - Gaucher's disease in a Zimbabwean toddler. PMID- 1893399 TI - Community control of schistosomiasis in Zimbabwe. AB - The community-based primary health care approach to control schistosomiasis morbidity is the strategy adopted in Zimbabwe. The paper outlines the results of such a control strategy in a rural community with over 30,000 people in the Madziwa area of Zimbabwe from 1985 to 1989. The community-based control strategy involved diagnosis of infection in school children (seven-15 years of age) using reagent strips followed by treatment with praziquantel. The treatment was linked to programmes aimed at improved sanitation, better water supplies and health education. Following chemotherapy, there was a marked reduction in schistosomiasis prevalence (urinary and intestinal forms combined) (from 60 to 20pc) in the affected groups. Of even greater importance was the significant reduction of 90pc in heavy infections (greater than 50 S. haematobium eggs per 10 ml of urine of greater than 100 S. mansoni eggs per gram of faeces). Progress made through chemotherapy was consolidated by the implementation of intervention measures aimed at reducing human water contact with cercariae infested water. In the last three years of the community-based programme, 2,152 improved ventilated pit latrines were constructed and 104 hand pumps installed at new or existing water points. Drama competitions at schools showed great potential in communicating health education messages. However, technical and organisational difficulties limited the impact of the health education to the general population. A single application of the synthetic molluscicide Bayluscide was carried out in the main streams at the beginning of the programme in support of the initial chemotherapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1893400 TI - The distinctive value of temperature pattern in liver cirrhosis and abdominal tuberculosis. AB - We assessed the temperature pattern in liver cirrhosis and abdominal tuberculosis during the first week of admission, before institution of definitive therapy. In 22 patients with liver cirrhosis, 59.19pc had subnormal temperatures and 9.1pc were pyretic. In 19 patients with abdominal tuberculosis, 31.6pc had subnormal temperatures and 36.8pc were pyretic (P less than 0.05). The group mean temperature of the cirrhotic patients lies within the subnormal temperature range while that of patients with abdominal tuberculosis lies within the normal range. This study suggests that patients with liver cirrhosis tend to develop subnormal temperatures much more than those with abdominal tuberculosis while pyrexia was commoner in the latter. The pattern of a carefully recorded and charted temperature can thus be of added distinctive value in situations where liver cirrhosis and abdominal tuberculosis pose diagnostic problems, where definitive diagnosis cannot be readily made or is delayed as a result of inadequate facilities. PMID- 1893401 TI - Antimicrobial activities of ziziphus abyssinica and berchemia discolor. AB - Aqueous, petroleum-ether, chloroform and dichloromethane extracts of both the barks and leaves of Ziziphus abyssinica and Berchemia discolor were tested for activity against Staphylococcus aureus, Escherichia coli and Candida albicans using the hole plate diffusion and the test tube dilution methods. The aqueous extracts showed significant activity against S. aureus and C. albicans. PMID- 1893403 TI - Infantile hypertrophic pyloric stenosis in Dar Es Salaam. AB - A five-year review revealed that 15 infants with hypertrophic pyloric stenosis were managed in Muhimbili Medical Centre. All belonged to parents residing within Dar es Salaam city: 12 were African, two Arabs and one was an Indian. the M.F ratio was 6'5:1. The approximate incidence rate was found to be one in 5,500 births. The majority presented with the characteristic clinical picture of the surgical condition and all were managed by the standard Fredet-Ramstedt pyloromyotomy. Mortality was 6.7pc. PMID- 1893402 TI - Carriage of Staphylococcus aureus among hospital personnel in a Nigerian hospital environment. AB - Among the 395 hospital staff examined during this study, 35.2pc of them were found to carry S. aureus in their anterior nares. The carriage was slightly higher in females (35.8pc) compared with 34.4pc in males, although it was not statistically significant. When the different age groups and professions were considered, the carriage was highest among the age group of 21-30 years and with the Nursing staff, who incidentally, are closest to the patients and had the highest number among the staff members examined. The carrier rate was also significantly higher (P less than 0.05) among staff members who had worked in the hospital for 7-10 months compared with other staff. There was a good correlation (97pc) between coagulase positivity and mannitol fermentation, while Methicillin, Claforan and Gentamycin were found to be very effective against most of the isolates. On re-examination of those staff members who ar closely associated with the patients two years after the initial exercise in 1987, it was evident that a significant number (P less than 0.05) of those carriers of Staph aureus in our hospital are not persistent ones. PMID- 1893404 TI - Carbamazepine-induced Diabetes mellitus. AB - Diabetes Mellitus was observed in a patient given carbamazepine. The diabetes improved when the treatment was discontinued and worsened on re-introduction. PMID- 1893405 TI - How should we investigate TIAs. PMID- 1893406 TI - Induction of macrophage TNF alpha, IL-1, IL-6, and PGE2 production by DTH initiating factors. AB - The elicitation of delayed-type hypersensitivity (DTH) reactions in mice is due to the sequential action of two different, antigen-specific, Thy-1+ cells. We have previously cloned the early-acting DTH-initiating cell from nude mice that were immunized and boosted by contact sensitization with oxazolone (OX). This cell clone, WP-3.27, releases an antigen-specific factor (OX-F) that sensitizes mast cells such that specific antigen challenge will induce serotonin release which mediates the early phase of DTH. In normal mice contact sensitized with picryl chloride (PCl), a similar polyclonal factor (PCl-F) has a similar activity and is also known to bind to macrophages. Thus, we measured macrophage production of TNF alpha, IL-1, IL-6, and PGE2 in response to the hapten affinity-purified DTH-initiating factors OX-F and PCl-F. Both factors induced significant release of each cytokine and PGE2. The production of TNF alpha, IL-1, and IL-6 was measured by bioassays. Northern blot analysis showed rapid accumulation of cytokine mRNA (2-4 hr), while maximal production of PGE2 occurred at approximately 8 hr. These macrophage activating properties of OX-F and PCl-F were not due to contamination with LPS as determined by the low levels of LPS present in OX-F and PCl-F and by the failure of polymyxin B to inhibit factor-induced PGE2 and TNF alpha production. Also, macrophage activation was shown not to be due to the action of several lymphokines known to be produced by WP3.27. Separation of OX-F and PCl-F by preparative isoelectric focusing showed a similar pattern: there were two major peaks of PGE2-inducing activity observed for both factors (for PCl-F at pI of 2-3 and 5.0, and for OX-F at pI of 3.5-4 and 5.0), but not for a sham factor produced by WEHI-3 cells. The ability of DTH-initiating factors to rapidly induce macrophage cytokine release and PGE2 synthesis 4-6 hr later may suggest a role for these mediators during the respective early vascular and late cellular phases of inflammation in DTH. PMID- 1893407 TI - Changes in expression of J11d on murine B cells during activation and generation of memory. AB - J11d is an antigen expressed on a variety of hemopoietic cells including B cells. In this report we describe the expression of J11d on functional subpopulations of B cells from adult mice of different ages or at different stages of an immune response. In addition we explore the relationship between the expression of J11d and that of other markers characteristic of memory B cells. Our results show that expression of J11d on B cells is related to the immunologic history of the host. Thus, J11d on B cells from normal mice is decreased as the mice age and are thereby exposed to environmental antigens. Down-regulation of J11d on B cells does not occur in germfree or nude mice but does occur when nude mice are reconstituted with T cells and/or are immunized. Since B cells expressing low levels of J11d accumulate following exposure to antigens, we also determined whether memory cells reside in the J11dlo cell population. To this end, we studied primed mice and found that expression of J11d on antigen-specific B cells increased during the first week after immunization and decreased thereafter. Increases in expression of J11d after activation also occurred in B cells stimulated with lipopolysaccharide (LPS) in vitro. However, antigen-specific B cells from long-term primed mice which expressed lower levels of J11d and antigen specific receptors of higher affinity also expressed lower densities of sIgM and included most sIgG+ cells. Furthermore, these antigen-specific J11dlo B cells transferred a memory response, whereas J11dhi cells did not. Taken together, these data indicate that the level of expression of J11d on B cells distinguishes virgin (J11dhi) from memory (J11dlo) cells in mice. PMID- 1893409 TI - [Determination of mefenoxalone in substances, tablets and biological materials]. AB - For the determination of mefenoxalon in substance, tablets and biological material (blood plasma), four variants were worked out. The first of them is based on the substitution of the benzene ring with bromine with the use of an excess of bromine, which is determined ionometrically. The second variant is based on direct titration of the hydrolytic product mefenoxalon, 3-(2 methoxyphenoxy)-2-hydroxypropylamine, with the use of the ion-selective electrode of the coated-wire type with a volumetric solution of tetraphenyl-borsodium. The third variant utilizes direct measurements of UV spectra of mefenoxalon in a solution of dichlorethane. The fourth variant consists in its fluorimetric measurement in a solution of dichlorethane, or ethylacetate. A detailed discussion of advantages and disadvantages of all above-mentioned variants of determination is presented. PMID- 1893408 TI - T cell non-MHC-restricted antigen-binding molecules secreted or associated with the cell membrane are antigenically distinct. AB - Some T cells produce membrane-associated or soluble molecules which bind nominal antigen specifically (TABM) and effect immunoregulation or events similar to cell mediated hypersensitivity. We have used polyclonal antisera raised against an azobenzene arsonate (ABA)-specific TABM secreted by an ABA-specific T cell hybrid or against TNP-specific polypeptides produced by immunoregulatory T cells to identify the expression of soluble (secreted) or membrane-associated TABM. Ascites fluid or culture medium containing a T cell hybrid or T cell lines, respectively, contain TABM recognized only by an antiserum specific for the secreted T cell hybrid (ABA-specific) derived TABM. Conversely, an antiserum that recognized the TNP-specific polypeptides detected cell-membrane associated TABM but did not bind TABM secreted by the T cell hybrid or cell lines. PMID- 1893410 TI - [Standard preparations for drug control]. PMID- 1893411 TI - [The 1891 Jubilee National Exhibition and Czech pharmacy]. AB - A hundred years ago, the Pharmaceutical Society in Prague, on the initiative of PhMr. H. Rudiger, the then pharmacist in Kralupy, and with great participation of PhMr. K. Schurer, the then owner of a firm furnishing pharmacies, participated in the Jubilee Country's Exhibition from May 15 to October 18, 1891 in Prague. Sixteen Czech pharmacists exhibited the products of their laboratories and manufacturing plants, galenical and chemical preparations and the first "specialities of pharmacies", personal and home medicine-cases and various adjusting and auxiliary material (such as bottles and ointment jars), "medicinal wafers" and the pertinent devices for their closing (PhMr. Fr. Sevcik from Prague). K. Schurer exhibited a complete equipment of a modern pharmacy with glass and porcelain drug jars and various pharmaceutical utensils. It was for the first time that pharmaceutical historical material, documentary and literary items were exhibited for the general public. The top exhibit was the Prague baroque pharmacy "The Golden Crown", which was donated to the National Museum in Prague when the exhibition was closed. The exhibition was put under a boycott by some German industrialists and the German pharmacists from Bohemia ostentatiously rejected any participation. The exhibition and its pharmaceutical part thus resulted in a distinguished achievement of Czech effort and work. PMID- 1893412 TI - [Assisted reproduction in the treatment of infertile marriages]. AB - The authors investigated how treatment of infertile marriages is affected by the introduction of assisted reproduction. They compared the five-year period 1978 1982--485 couples with group II (1983-1987)--787 married couples. In group II successively all methods of assisted reproduction were introduced. The authors found that group II (1983-1987) had by 18.3% more deliveries, as compared with the first period. The increase is due to assisted reproduction in 10.6% and due to other therapeutic methods in 7.7%. The increase occurred in all investigated indication groups using methods of assisted reproduction within the range of 6.9 14.4%. PMID- 1893413 TI - [Antibiotic prophylaxis in cesarean section]. PMID- 1893414 TI - [Myasthenia gravis and pregnancy]. PMID- 1893416 TI - [Use of computers in gynecology and obstetrics. Selected reports presented at the National Scientific Conference of the Czechoslovak Gynecologic-Obstetrical Society held in Bratislava May 3-4 1990]. PMID- 1893415 TI - [Possibilities and tasks of the Czech Obstetrical and Gynecologic Society from the viewpoint of the Secretary]. PMID- 1893417 TI - [Prenatal diagnosis. Premature labor. Disorders of the menstrual cycle. Selections from reports presented at the 5th National Gynecology-Obstetrical Conference, Bratislava, June 6-8 1990]. PMID- 1893418 TI - [Hypoxic pulmonary hypertension]. PMID- 1893419 TI - [Subsidiary rhythmicity in the area of the coronary sinus]. PMID- 1893420 TI - [The effect of therapy in arterial hypertension on serum proteins in animals surviving for a long period with an artificial heart]. PMID- 1893421 TI - [Experimental liver cirrhosis in laboratory rats]. PMID- 1893422 TI - [Modification of the open system of indirect calorimetry for neonates: standardization of the method]. PMID- 1893423 TI - [The role of the thalamus in controlling motor function]. PMID- 1893424 TI - [Genodermatoses in fetal skin biopsies]. AB - The risk of serious genodermatoses, i. e. mainly of bullous epidermolyses and keratinization lesions, can be verified only by a prenatal ultrastructural diagnosis. In a group of 23 biopsies of fetal skin the diagnosis of genodermatosis was proved in 10 cases and denied in 10 cases, 3 samples were useless. Discussion points out technological prerequisites of fetal skin biopsy and interpretation problems of ultrastructural diagnostic phenomena in genodermatoses. PMID- 1893426 TI - [Evaluation of the biological behavior of uterine smooth muscle tumors]. AB - Macroscopical and histological findings in 10 uterine leiomyosarcomas served for evaluation of their biological behaviour according to clinical data and contemporary histological criteria. The authors stressed a need of complex analysis in less definite cases and recommended considering other clinical, macroscopical and microscopical features of malignancy in addition to mitotic rate for diagnosis of leiomyosarcoma. PMID- 1893425 TI - [Expression of A,B and H blood group antigens in urothelial carcinoma of the urinary bladder]. AB - Expression of blood group antigens A, B, and H was studied in transitional carcinoma of the urinary bladder. Positive result was obtained in 16 cases of a group of 21 tumours by indirect immunoperoxidase reaction with monoclonal antibodies. A relation of quantitative expression to histological grading of tumour differentiation was noticed. Well differentiated transitional carcinomas mostly had more conspicuous expression of A, B, and H antigens. However, expected more favourable prognosis in cases of transitional carcinoma with expression of A, B, and H blood group antigens failed to be proved. PMID- 1893427 TI - [Aggressive angiomyxoma of the female pelvis and perineum, M-8841/1]. AB - Aggressive angiomyxoma of pelvis and perineum was identified in two women (of 31 and 53). Its site was in the right fossa ischiorectalis and vulva. There was not observed any relaps in 60 and/or 9 months after surgery. Amorphous tumour mass was soft with finger-like projections. Spindle and starshaped tumour cells were spread in a loose edematous myxoid vascularized stroma; they had a benign character lacking of mitoses and nuclear atypia. Myxoid stroma could be stained rather faintly with Alcian blue at pH 1. Dilated capillaries, veins and arterioles were a substantial component of the tumour. Nerve and muscle fibres and their fragments were included here and there in the tumour. Tumour cells had a fibroblast ultrastructure which was supported by immunohistology. Discussion comprised differential diagnosis of myxoma, myxoid liposarcoma and myxoid type malignant fibrous histiocytoma among others. PMID- 1893428 TI - [Histological diagnosis of epithelial tumors of the skin using an expert system]. AB - Database for histooncological diagnosis of epithelial skin tumours was tested on 32 verified cases from the Hlava Institute files. Expert systems Fel-Expert 2.9 produced a correct diagnosis in 19 cases, was partially correct in 11 cases and quite uncorrect in 2 cases. Causes of diagnostic dissent and tuning problems of the database were discussed. PMID- 1893429 TI - [A program for automated histomorphometry of bone tissue]. AB - A programme for controlled automated histomorphometric evaluation of bone biopsies, connected with authors' results with semiautomated program, introduces new technology as well as new principle. It is based on a digitalization of microscopic picture in videocamera followed by controlled automated computerized processing of the picture. A further simplification of the evaluation process is achieved by eliminating a time consuming and not quite precise over-drawing of the picture on a digitalization desk. PMID- 1893431 TI - [Difficulties in the diagnosis of Gaucher's disease]. AB - The first diagnostic phase of Gaucher's disease is based on correct evaluation of clinical history as well as on finding of typical striated Gaucher's cells in bone marrow. Nevertheless, there can occur surprising diagnostic faults in spite of believed easy identification of this classic storage disease. They can be caused by a primary atypical or secondary modified clinical phenotype. Another source of diagnostic error or hesitation can be in an atypical appearance of Gaucher's cells because of poorly distinct cytoplasmic striation (solid voluminous cytoplasm) or classical vacuolized pattern. PMID- 1893430 TI - [Diagnosis of G(M2) gangliosidosis in routine practice]. AB - Diagnosis of GM2 gangliosidosis and other most frequent thesaurismoses of the central nervous system was exposed on a case of a 2-year-old boy. Diagnostic process which exploited routine methods commonly used in every department of pathology enabled to choose chemical and enzymological investigation of brain tissue. PMID- 1893432 TI - [Defects of the atrioventricular cardiac septum (persistent common atrioventricular canal)]. AB - A new morphological-clinical classification was suggested for this type of heart malformations based on confrontation of authors' results with literature. The classification took into consideration appearance of the top of ventricular septum, form of atrioventricular valves, topography of the defect and its relation to the location of conducting system. PMID- 1893433 TI - [Long-term prognosis in children with minor glomerular abnormalities]. AB - The authors evaluated the course and prognosis of the disease in 109 children with minor glomerular abnormalities manifested clinically in 45.9% as nephrotic syndrome (NS), in 33% as nephritic syndrome (GN), in 11.9% as isolated haematuria (IH) and in 9.2% as Schonlein-Henoch's purpura (PSH). In NS 78% of the children had before biopsy of the kidneys frequent relapses, 22% were resistant to cortisonoids. After biopsy all children were given cortisonoids, 94% immunosuppressive treatment with cytostatics and some of the children additional treatment. The number of resistant cases declined to 10% and the mean number of relapses from four to one in 12 months. Children under five years had more relapses (P less than 0.05) but also more complete remissions (P less than 0.001) than older children. Relapses occurred up to 10.2 years after the onset of the disease (mean = 4 years). With advancing age and duration of the disease their number declined after treatment. An adverse symptom was resistance to cortisonoids and immunosuppressive treatment, major haematuria and persisting hypertension but not immunological activity (elevated level of immune complexes, reduced C3, positive immunohistochemical finding in renal tissue). The morphological finding which at the onset was slightly beyond the range of minor abnormalities had a poorer prognosis when associated with greater clinical activity. The group developed 88% complete remissions and 6% CHRI. After 22 years the probability of survival in complete continual remission is 66%, the probability in CHRI is 10% (with morphological progression). In nephritic syndrome the children were given after biopsy prednisone in 80.6% and cytostatics in 44.4%. In PSH this treatment was given to 100% and 60% of the children, in IH to 61.5% and 7.7%. On evaluation in nephritic syndrome complete remission was recorded in 47.2%, after 0.4-10.5 years since the onset of the disease; 30.6% did not improve and in 2.8% CHRI developed. In PSH remission developed in 60% after 0.8-6.9 years, no improvement was recorded in 20%, incl. 10% where CHRI developed after a resistant course of NS. In IH 84.6% of the patients did not improve, but in none the renal function deteriorated. The course was in all instances milder than in NS, most frequently only with microscopic haematuria and/or slight proteinuria, respectively minor immunological activity. In the entire group of minor glomerular abnormalities complete remission was achieved in two-thirds of the children, in one quarter the disease did not improve, incl. 4.6% where CHRI developed, always associated with progression of morphological changes.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1893434 TI - [Results of the diagnosis of nodular goiter in children]. AB - The authors submit diagnostic conclusions in 28 children with nodular goitre aged 7-15 years. Twenty-four children had a mononodular goitre and 4 a multinodular one. Sixteen children were operated and histological examination revealed three times adenoma, twice carcinoma, three times a colloid node, four times a cyst and four times lymphatic thyroiditis. In 10 non-operated children in one a cyst was found and in nine lymphocytic thyroiditis. The authors submit diagnostic conclusions in 28 of different examination methods in the differential diagnosis of nodular goitre in children--red cell sedimentation rate, haemogram, X-ray of the lungs, palpation functional examination of the thyroid gland, sonography, scintigraphy, assessment of autoantibodies, hormonal suppression, aspiration cytology and histological examination. PMID- 1893435 TI - [Gastroesophageal reflux as the basis of recurrent and chronic respiratory diseases]. AB - Among many causes of relapsing and chronic respiratory diseases in children the authors revealed gastrooesophageal reflux (GER) in 53 of 106 examined children, i.e. in 50%. Therefore examination of GER was included in routine examinations of all children admitted on account of the following diseases: laryngitis rec., bronchitis rec., bronchitis obstructiva rec., pneumonia rec., bronchiectasy, bronchitis deformans, asthma bronchiale. GER was detected in 208 children aged 6 months to 15 years. All children were subjected to an X-ray examination by contrast substance and to sonography of the cardia. In clinically serious cases manometric and pH metric examinations were made. When GER was detected the authors recommended conservative treatment: postural position, restricted fluid intake before going to bed, elimination of cocoa and chocolate, antacids. A favourable effect of conservative treatment in the course of 1-2 years was recorded in 60 of 76 children, who attended check-up examinations, i. e. in 79%. In children where serious complaints persisted, in particular rec. pneumonia, the development of deforming bronchitis and bronchiectasy or dyspnoic attacks, the authors indicated after completion of examinations and agreement with surgeons, a surgical approach. Fundoplication was performed in 22 children, i. e. in 10% of the patients where GER was revealed. PMID- 1893436 TI - [The effect of enalapril on the development of diabetic nephropathy in children and adolescents]. AB - Diabetic nephropathy is the most frequent cause of chronic renal insufficiency in adults. Its early stage, characterized by increased albuminuria, develops in susceptible subjects already manifestation of diabetes. This stage can be treated by inhibitors of the angiotensin-converting enzyme which reduce the pathologically elevated intraglomerular pressure even in normotonic subjects. Enalapril was administered for a period of 12 weeks to eight children and adolescents with a normal blood pressure and albuminuria of 30-300 mg/24 hours during repeated assessments. During treatment there was not only a significant decline of albuminuria (from 104.6 +/- 42.7 mg/24 hours to 47.2 +/- 15.4, p = 0.003) but also a drop of the pathological glomerular hyperfiltration (from 3.38 +/- 1.87 ml/s to 1.48 +/- 0.54 ml/s within six weeks - p = 0.02 and to 2.05 +/- 0.80 ml/s resp. within 12 weeks, n.s.). The favourable effect persisted also for some time after discontinuation of treatment. Treatment was relatively well tolerated by the patients. The problem remains whether it is possible to retard or prevent in this way the development of further stages of diabetic nephropathy, include chronic renal failure. PMID- 1893437 TI - [Hereditary nephropathy with signs of nephrotic syndrome]. AB - The authors submit the description of two sisters with hereditary nephropathy, with symptoms of nephrotic syndrome. In the clinical picture dominated permanent anuria, rapid renal failure and death at the end of neonatal age. Histopathological findings classified the disease as infantile diffuse mesangial sclerosis. The third patient is a sporadic case of primary congenital nephrotic syndrome. PMID- 1893438 TI - [What do we know about histamine?]. PMID- 1893439 TI - [New findings on the virology and immunology of AIDS]. PMID- 1893440 TI - [The role of bronchoalveolar lavage in the diagnosis and therapy of recurrent respiratory tract diseases in children]. AB - In 32 patients with relapsing bronchopneumonia, bronchiectasis, relapsing obstructive bronchitis and asthma bronchiale during aimed bronchoscopy bronchoalveolar lavage was made (BAL). The authors found typical cytological findings and deviations in the phosphatidyl choline level which is the main constituent of the pulmonary surfactant. The authors evaluated the importance of the surfactant for the proper function of the lungs and outlined possible therapeutic measures which by the action of some drugs will influence its formation. PMID- 1893442 TI - [Nutrition and hyperbilirubinemia in normal neonates]. PMID- 1893441 TI - [The intra-atrial-reentry type of supraventricular paroxysmal tachycardia]. AB - The authors describe a 10-year-old girl with supraventricular paroxysmal tachycardia of the intraatrial reentry type. The diagnosis was confirmed by Holter and electrophysiological examination. Therapeutic possibilities are discussed. PMID- 1893443 TI - [Thyroid gland volumetry using real-time sonography in children and adolescents in the Prague 10 District]. AB - In 245 healthy children from Prague 10 sonographic examinations of the thyroid were made to assess normal values of the volume of the thyroid gland. The children were 5 days to 18 years old, healthy according to the case-history and clinical examination, and neonates also according to biochemical tests. The volume was calculated according to Brunn's formula, i. e. a. b. c. 0.479 (1). The results were compared with age, height and weight of the examined children and are presented in a table. PMID- 1893444 TI - [Neurologic complications after vaccinations]. PMID- 1893445 TI - [Emancipation and motherhood]. PMID- 1893446 TI - [The daily schedule of children attending nurseries]. AB - Evaluation of data in questionnaire completed by the health community paediatrician in February 1984 and 1985 in cooperation with one of the parents of 94 2-3-year-old children attending nurseries in Bratislava (Vth district) revealed that 18% of the children spend too much time (10-10.5 hours per day) in the nursery. The assumption was confirmed that in winter the children do not spend enough time outdoors, not only on working days (50% of the children go home from the nursery straight way) but also on non-working days (37.2% of the children spend less than two hours outdoors). This can have a negative effect on the resistance against diseases, in particular of the respiratory system. PMID- 1893447 TI - [Report on the activity of the School Health Care Committee of the Czech Pediatric Society]. PMID- 1893448 TI - [Cooperation between pediatrics and rehabilitation medicine]. PMID- 1893449 TI - [Sunbathing in children]. PMID- 1893450 TI - [A declaration of children's rights]. PMID- 1893451 TI - [The solitary kidney in children and adolescents. Morphologic and functional characteristics]. AB - Reduction of the renal parenchyma in experimental animals can cause glomerulosclerosis in the single kidney and lead sometimes to functional failure. Data on the influence of nephrectomy or agenesis on the later fate of the patient in human medicine are controversial. The authors examined a total of 40 patients with single kidneys. In 23 agenesis was involved (15 boys, 8 girls) aged 6-22 years (mean = 11.9, s = 4.3). In 17 nephrectomy was performed (9 boys, 8 girls); time interval after nephrectomy 1-26 years (mean = 7.8, s = 3.9). Three quarters of all patients excreted increased amounts of albumin (detected as microalbuminuria by immunoturbidometry). The glomerular filtration rate (GFR) was slightly reduced in about one third of the patients but none suffered from renal insufficiency. In one half of the group the authors detected a slightly impaired concentrating capacity with an increased sodium fraction. In one third marginal diastolic hypertension was recorded. In half the group the single kidney was hypertrophic. Regression analysis did not reveal deterioration of the GFR in relation to age but revealed increasing renal hypertrophy in relation to height with accelerated hypertrophy during puberty. There was also a significant drop of the systolic blood pressure in relation to age in patients with agenesis. In none of the other parameters differences were found between the group with agenesis and nephrectomy. Patients with a single kidney deserve prolonged ambulatory follow up. In the investigated group the single kidney influenced in a substantial way also the selection of occupation. PMID- 1893452 TI - [24-hour measurement of pH and its significance in the diagnosis of gastroesophageal reflux in children]. AB - During 1987-1989 the authors examined 57 patients; reflux disease was detected in 33 (i.e. 57.89%). In the group of patients where the indication for examination was based on symptomatology typical for respiratory diseases, they found a higher rate of positive findings--62%. The authors draw attention to some methodological problems of 24-hour pH-metry. They explain the advantages of the mentioned examination method in relation to the subsequent therapy. PMID- 1893453 TI - [Comparison of basic physical measurements in Czech and Slovak children and adolescents]. AB - The authors compared the Slovak and Czech part of the IVth nation-wide anthropological survey of children and youth from birth to the age of 18 years and evaluated the revealed differences in height, body weight, head and chest circumferences. The results confirm the assumed further approximation of growth values of the two child populations and the gradual equalization recorded in particular in the youngest age groups. PMID- 1893454 TI - [Diagnosis of Turner's syndrome 1965-1989: karyotype, age at diagnosis and determining signs]. AB - Early diagnosis of Turner's syndrome makes possible optimal application of all procedures of substitution and symptomatic therapy and offers also psychological support to the parents and the patients. In 1965-1989 in two centres 135 girls with Turner's syndrome were detected, 72 with karyotype 45, X, 63 with a chromosomal mosaic and/or structural anomaly. Girls and women with karyotype 45, X are detected sooner (9.4 +/- 6.9 years, as compared with 14.2 +/- 8.1 years, p = 0.0003). Before the age of three 28% of the girls with karyotype 45, X were detected (by congenital lymphoedemas, coarctation of the aorta, poor progress), only 9% of the others. Growth impairment revealed the diagnosis in 27% of the affected girls. Girls with karyotype 45, X were diagnosed on account of impaired growth sooner (7.9 +/- 2.2 years as compared with 11.8 +/- 2.7 years, p = 0.00005). At a time when the diagnosis of girls with karyotype was practically completed, 16% of the spontaneously maturing and menstruating women with chromosomal mosaic where the syndrome was detected during examination of sterility or habitual abortion were still not diagnosed. PMID- 1893455 TI - [Theoretical discussion of behavioral approaches in the treatment of obesity]. PMID- 1893456 TI - [An outbreak of hemolytic-uremic syndrome associated with findings of verotoxin producing Escherichia coli (VTEC)]. PMID- 1893457 TI - [Persistent pulmonary hypertension in a neonate]. AB - The author gives an account of recent findings on the pathophysiology and treatment of persisting pulmonary hypertension in a neonate. His own experience with treatment is documented in case-histories. He emphasizes the marked therapeutic effect of hyperoxic hyperventilation. PMID- 1893458 TI - [Central (true) precocious idiopathic puberty--therapeutic possibilities]. PMID- 1893459 TI - [Pulmonary hypertension in children after radical operations for congenital heart defects]. PMID- 1893460 TI - [The fate of children endangered by their own family]. PMID- 1893461 TI - [Postpartum adaptation of hypotrophic neonates as manifested by excretion of hydrogen ions in the urine]. PMID- 1893462 TI - [Disorders of the cardiovascular system in congenital lentiginosis]. AB - The authors investigated during the last 10 years four patients with lentiginosis and affection of the heart. In none of them the symptoms were complete enough to include it under the leopard syndrome. In two patients the authors found changes in the outflow portion of the right ventricle which was in their opinion caused by hypertrophy of the interventricular septum and musculature of the right ventricle. The authors consider the term lentiginocardiomyopathic syndrome suitable for this rare clinical and genetic entity. The authors check patients with lentiginocardiomyopathic syndrome regularly after 6-month intervals. In two children they recorded progression of the heart disease. PMID- 1893463 TI - [A Czech physician at the birth of pediatric medicine]. AB - The author draws attention to the Czech physician J.J. Mastalir, who founded at the end of the 18th century in Vienna a surgery for poor sick children, one of the first ones in Europe. His work is briefly compared with that of the Prague obstetrician Dr. J. Melic who worked during the same period along similar lines in Prague. PMID- 1893464 TI - [Sonographic analysis of postextubation stridor in neonates and children with low birth weight after long-term artificial ventilation]. AB - In a group of 23 neonates with mean birth weights of 1470 g (range 1200-3980 g) who had orotracheal intubation for an average period of 12.6 days (range 5-96 days) sonagraphic frequency analysis of 86 stridors 1-3 hours after intubation was performed. According to the results of the frequency analysis more than 97.6% of the stridors are supraglottic (84 of 86 analyzed stridors). The laryngeal and tracheal type of stridor was recorded only in two children. The finding is surprising and does not confirm the widely accepted view that neonates after extubation are threatened with oedema of the larynx or stricture at this or a distal level. As elective postextubation laryngoscopy is controversial, acoustic frequency analysis of stridor after extubation is a suitable alternate method in investigations of the clinical condition of the infant and serves the clinician as an indication on the level of stenosis of the airways. PMID- 1893465 TI - [Treatment of Hodgkin's malignant lymphoma in children and adolescents by immunomodulation with a dialysate of human leukocytes]. AB - The authors assessed in a group of children with malignant lymphoma the effect of dialysate of human leucocytes on some immunological indicators. Assessment of T lymphocytes by the E rosette test before and after administration of a dialysate of human leucocytes did not reveal any significant changes in the number of T lymphocytes. Similarly the assessed number of NK cells in the peripheral blood stream was not markedly affected. The immunostimulating action was manifested by an increased activation of lymphocytes assessed by the nuclear test and the blastic transformation test. In lymphocytic sub-populations examined by means of monoclonal antibodies a rise of CD4+ and T lymphocytes was recorded. PMID- 1893466 TI - [Comparison of physical growth in school-children living in children's residential facilities and in families with emphasis on the gypsy ethnic group]. AB - The authors investigated the growth of 1208 gipsy and non-gipsy children living with their families and in childrens homes. They revealed that gipsy children from childrens homes were shorter, lighter and had a smaller chest circumference as compared with gipsy children living with their families. This applied only to younger school children. Somatic development caught up in boys at the age of 11 12 years and in girls approximately 1-2 years sooner. The values of the body mass index in boys declined with age. In girls this decline was found only up to the age of 11 to 12 years. Non-gipsy children from childrens homes were smaller than non-gipsy children according to Slovak standards (Lipkova et al.; 5); this was particularly marked in boys. The authors found also that the somatic development of gipsy children from childrens homes oscillates between the somatic development of non-gipsy children according to the Slovak standards and the somatic development of gipsy children from families but only during later school age. PMID- 1893467 TI - [Carotenemia]. AB - The authors demonstrate two infants with a yellow skin coloration which developed as a result of excessive dietary carotenoid intake. The yellow coloration, contrary to jaundice, did not affect the sclerae. Elevated blood carotenoid levels were found and a temporary increase of aminotransferases. In both infants lower IgA levels were recorded. After modification of the diet the yellow coloration disappeared and gradually the aminotransferases reached normal levels. PMID- 1893468 TI - [Fever from the viewpoint of the pediatrician]. PMID- 1893469 TI - [Characteristics of cardiorespiratory function in the sudden infant death syndrome]. PMID- 1893470 TI - [Development of symptoms of depressive syndrome in childhood]. AB - The author summarizes briefly views on the depressive syndrome in childhood during past decades as well as contemporary views. She mentions basic aetiopathogenetic factors participating in the development of depression during childhood. She explains why the clinical picture changes in relation to the age of the child patients. The author presents als the results of an investigated group of 120 depressive child patients and discusses different clinical symptoms, their frequency, interrelationship, age-related character. She uses the following categories: junior school child under 11 years, senior school child under 14 years, adolescent above 14 years. Based on an analysis of the results the author describes the changes and development of the clinical picture in depressive syndrome in children. Finally she emphasizes that it is useful to collaborate with paediatricians when treating children with depressive syndrome. PMID- 1893471 TI - [Development of the human body in relation to basic functions of the major body systems. Results of the major tasks of the VIII-3-3 National Plan for Basic Research for 1986-1990]. PMID- 1893472 TI - [Indications, advantages and pitfalls of modern imaging methods in childhood and adolescence]. PMID- 1893473 TI - [Idiopathic hypercalciuria--a cause of hematuria in children]. PMID- 1893474 TI - [The significance of chemiluminescence in the diagnosis of disorders of phagocytosis in neonates]. PMID- 1893475 TI - [Herpes infections in neonates]. PMID- 1893476 TI - [Administration of erythromycin]. PMID- 1893478 TI - The distribution of MNSs blood groups in Sri Lanka and their significance in paternity testing. AB - MNSs blood grouping was done on a random sample of 700 blood donors at the Central Blood Bank and at some of the Mobile Units, from September 1980 to August 1981. The distribution of M,N, Ss and combined MNSs phenotypes and their corresponding genotypes among Sri Lankans was evaluated. The frequencies of these phenotypes are different from those of Caucasians. The significance of MNSs blood grouping in the investigation of doubtful paternity is discussed. PMID- 1893477 TI - Congenital syphilis--the forgotten disease. PMID- 1893479 TI - Is there a need to change the format of the post-mortem examination report form Health 42? PMID- 1893480 TI - A convenient, reproducible method of charting eye movements, pupils and ptosis. PMID- 1893481 TI - Recognition and management of functional complaints. PMID- 1893482 TI - History of teaching hospitals in Sri Lanka. General Hospital Colombo (1). PMID- 1893483 TI - About ourselves. PMID- 1893484 TI - Lipid patterns and dietary habits of healthy subjects living in urban, suburban and rural areas. AB - Lipid patterns were determined in 167 healthy subjects in the age group 28 to 50 years living in an urban area, a suburban area and two rural areas to determine a possible relationship between their serum lipid patterns and food habits. Total cholesterol, high density lipoprotein (HDL)-cholesterol, and triglyceride concentrations were determined in the sera of fasting subjects, and low density lipoprotein (LDL)-cholesterol concentration was calculated. Risk of coronary heart disease as assessed by the body mass index, ratios of total cholesterol to HDL-cholesterol, and LDL-cholesterol to HDL-cholesterol, was significantly lower in subjects in rural area 2, who were agricultural workers with a high degree of physical activity, subsisting on a diet consisting mainly of plant food, despite a higher consumption of coconut, a saturated fat. It is possible that the hypercholesterolaemic effect of saturated fats was mitigated by the high fibre content of their diets. PMID- 1893485 TI - Targeting of liposomes surface-modified with glycyrrhizin to the liver. I. Preparation and biological disposition. AB - We consider glycyrrhizin to be a new ligand for liposomes to the liver because it is known that about 80% of glycyrrhizin is excreted into the bile after intravenous administration in rats. In order to modify the liposomal surface with glycyrrhizin, 30-stearyl glycyrrhizin (GLOSt), one of the lipophilic glycyrrhizin derivatives, was synthesized. The structure of this new compound was identified by nuclear magnetic resonance (NMR), infrared (IR) and mass spectra (MS). Sonicated liposomes were prepared from hydrogenated egg phosphatidylcholine cholesterol-GLOSt or dicetyl phosphate (DCP) (4:4:1) and were labelled with [3H]inulin as an aqueous marker. It was confirmed by measuring the encapsulation efficiencies and the mean diameters that GLOSt-containing sonicated liposomes (GLOSt-SUV) were SUV-type as well as DCP-containing control liposomes (control SUV). Four hours after intravenous injection into rats at a dose of 90 mumol as total lipid per kg of rat body weight, GLOSt-SUV showed 4-fold more accumulation (42.4%) in the liver than control-SUV. Therefore, glycyrrhizin is considered to be a useful new ligand on liposomes for targeting to the liver. PMID- 1893486 TI - Possibility of heat sterilization of liposomes. AB - Several kinds of liposomes were sterilized at 121 degrees C for 20 min. They tended to aggregate after heat sterilization (HS) in saline, while no aggregation was observed in an isotonized sugar or polyol solution. The dispersions containing egg phosphatidylcholine (EggPC) with a high peroxide value (POV) turned slightly yellowish after HS. This color change was prevented by using EggPC with a low POV, hydrogenated EggPC (H-EggPC) or dipalmitoylphosphatidylcholine (DPPC). Nitrogen gas bubbling at neutral pH also prevented the color change, but vitamin E did not. The particle size of the EggPC liposomes extruded through a 0.4 micron membrane filter did not change significantly after HS, whereas the H-EggPC or DPPC liposomes extruded through a 0.8 micron membrane filter tended to be reduced in size. On this change the type of medium had a considerable influence. The anionic 6-carboxyfluorescein leaked from the negatively charged liposomes (EggPC/cholesterol (Chol)/egg phosphatidylglycerol) during HS, while no leakage was observed from the positively charged liposomes (EggPC/Chol/stearylamine) not only during HS but also during a long period of storage. It was suggested that sterilization of liposomes by heating was practicable as well as that by filtration, if the liposomes were prepared as follows: the charged liposomes made of lipids with low POV's were dispersed in a sugar or polyol solution adjusted to nearly pH 6.5, where the amount of dissolved oxygen was minimized. An ionic water-soluble drug had to be encapsulated in the oppositely charged liposomes. PMID- 1893487 TI - Synthesis of fluorine and iodine analogues of clorgyline and selective inhibition of monoamine oxidase A. AB - A series of fluorine and iodine analogues of clorgyline was synthesized and evaluated for inhibitory potency and selectivity toward monoamine oxidase A (MAO A). Among them, N-[3-(2,4-dichloro-6-iodophenoxy)propyl]-N-methyl-2-propynylami ne (3d), N-[3-(4-chloro-2-fluorophenoxy)propyl]-N-methyl-2-propynylamine (3f) and N-[3-(2-chloro-4-fluorophenoxy)propyl]-N-methyl-2-propynylamine (3g) were found to have high inhibitory potency and selectivity toward MAO-A comparable to those of clorgyline itself. Thus, they were considered for advanced development as radiofluorinated and radioiodinated ligands that may be useful for functional MAO A studies in the living brain with positron emission tomography and single photon emission computer tomography. PMID- 1893488 TI - A cytotoxic substance from Sangre de Grado. AB - Taspine has been isolated as a cytotoxic substance from Sangre de Grado, sap of Croton palanostigma (Euphorbiaceae), by bioassay guided fractionation. The cytotoxicity (IC50) of taspine was found to be 0.39 microgram/ml against KB cells and 0.17 microgram/ml against V-79 cells. PMID- 1893489 TI - Nematocidal principles in "oakmoss absolute" and nematocidal activity of 2,4 dihydroxybenzoates. AB - Nematocidal principles obtained from oakmoss absolute were identified as methyl 2,4-dihydroxy-3,6-di-methylbenzoate (2), ethyl 3-formyl-2,4-dihydroxy-6 methylbenzoate (4), and ethyl 5-chloro-3-formyl-2,4-dihydroxy-6-methylbenzoate (7). In relation to their structures, the nematocidal activity of 2,4 dihydroxybenzoates of methyl to tetradecyl was tested and the strongest activity was found in the octyl ester (minimal lethal concentration = 13 microM). PMID- 1893490 TI - Presence of the basement membrane component--heparan sulfate proteoglycan--in bovine lens capsules. AB - Heparan sulfate proteoglycan was extracted from bovine lens capsules by 0.45 M NaCl/2 M urea and purified using ion-exchange chromatography and gel filtration. The proteoglycan was found to consist of protein and carbohydrate in a ratio of 75 to 25. The estimated average molecular weight of the heparan sulfate proteoglycan eluted by 0.2 M NaCl on a diethylaminoethyl (DEAE)-cellulose column was 400 kilodaltons (kDa) and that of its glycosaminoglycan was 18.8 kDa. The amino acid composition of the proteoglycan was quite similar to that of the bovine glomelular basement membrane. PMID- 1893491 TI - Effect of L-cysteine on plasma concentration and urinary excretion of 1 (tetrahydro-2-furanyl)-5-fluorouracil metabolites. AB - Effects of L-cysteine (CySH) on the plasma concentrations and the urinary excretion of 1-(tetrahydro-2-furanyl)-5-fluorouracil (FT) and its metabolites were studied by high performance liquid chromatography in rats. Significantly higher plasma concentrations of FT, 5-fluorouracil (5-FU) and cis-4'-OH-FT were obtained after an oral administration of FT (500 mg/kg) combined orally with CySH (500 mg/kg) when compared to FT alone. The urinary excretions of 5-FU, trans-3' OH-FT, cis-4'-OH-FT, trans-4'-OH-FT and 4',5'-dehydro-FT significantly decreased up to 12 h but that of alpha-fluoro-beta-alanine significantly increased up to 24 h by the combined administration of CySH. Furthermore, the plasma concentration of 5-FU significantly increased at 0.5 h and its urinary excretion significantly decreased up to 4 h after an intraperitoneal administration of 5-FU (10 mg/kg) combined orally with CySH (500 mg/kg) when compared to 5-FU alone. The urinary pH significantly changed to acidic and the urinary volume significantly increased by the combined administration of CySH, so it was thought that the reabsorption of 5 FU through renal tubules from urine could increase and the increment of the urinary excretion of alpha-fluoro-beta-alanine was caused by this. Then it was suggested that the increase of the plasma concentrations of 5-FU and cis-4'-OH-FT could be attributed to the decrease of their urinary excretions after an administration of FT combined with CySH when compared to FT alone. PMID- 1893493 TI - Glycation of human serum albumin in long-term incubation with low and high concentrations of glucose. AB - Glycated albumin levels of incubation mixtures with high (25.8 mM) and low (8.2 mM) concentrations of glucose when measured by the nitroblue tetrazolium (NBT) reducing method, showed similar values at day 20-25. But when tested by thiobarbituric acid (TBA) colorimetry, the levels with high concentrations of glucose were about twice that with low concentration of glucose. PMID- 1893492 TI - Studies on an enzymatically synthesized antitumor polysaccharide SPR-901. AB - An antitumor polysaccharide SPR-901 was found in a fermented broth of a kind of lactic acid bacteria isolated from rice bran. SPR-901 is a high molecular alpha glucan and its linkages are almost linear alpha-1,6 glucosidic ones with a small amount (ca. 5%) of branches at C-3 positions. It is a highly purified alpha glucan and it contains no protein and no inorganic salts. SPR-901 showed significant antitumor activities against murine allogeneic and syngeneic tumors by both intraperitoneal and oral administration, and enhanced carbon clearance ability in mice, while it showed no direct cytotoxicities in vitro. The mechanism of antitumor activities of SPR-901 is supposed to be a host-mediated one, and this substance is classified as one of the biological response modifiers. These properties of SPR-901 were identical to those of RON, which was obtained from rice bran, therefore we concluded that these two polysaccharides were the same substance. PMID- 1893494 TI - Evaluation of effects of novel urease inhibitor, N-(pivaloyl)glycinohydroxamic acid on the formation of an infection bladder stone using a newly designed urolithiasis model in rats. AB - By using our new infection stone model of a rat, we evaluated the effect of a novel urease inhibitor, N-(pivaloyl)glycinohydroxamic acid (P-GHA), on the formation of an infection bladder stone. The oral dosing of P-GHA significantly inhibited the elevation of the urinary ammonia level of rats having the urinary tract infection with Proteus mirabilis. A short term regimen (7 d, 730 +/- 38 mg/kg) with P-GHA significantly inhibited the development of the infection bladder stone. Furthermore, a long term combination regimen (11 d) of P-GHA and aminobenzylpenicillin markedly inhibited the development of the infection bladder stone, and also caused a very slight renal impairment to the rats tested in contrast with the method of Vermeulen et al. Our infection stone model in rats, therefore, seems to be useful for the evaluation of therapeutic agents in long term examinations. PMID- 1893495 TI - Effects of a novel urease inhibitor, N-(diaminophosphinyl)isopentenoylamide on the infection stone in rats. AB - We evaluated the effect of a novel potent urease inhibitor, N (diaminophosphinyl)isopentenoylamide (IPA), on the development of an infection bladder stone using our urolithiasis model in rats. IPA was excreted into urine after oral administration to rats, and the cumulative urinary recovery rate of unchanged IPA reached about 29.6% within 24 h (50 mg/kg). The oral administration of IPA (6.25 mg/kg, b.i.d., 5 d) significantly inhibited the development of the infection bladder stone. The present result suggests that IPA is a very promising compound in the prevention of formation and recurrence of an infection stone owing to a high efficacy and a low toxicity of IPA in animals. PMID- 1893496 TI - Studies on cardiotonic agents. VII. Potent cardiotonic agent KF15232 with myofibrillar Ca2+ sensitizing effect. AB - A series of novel 4,5-dihydro-5-methyl-6-(2 or 4-substituted 7-quinazolinyl) 3(2H)-pyridazinones was synthesized and examined for cardiotonic activity in anesthetized dogs. The 4-substituted aminoquinazolines generally showed potent and long-lasting inotropic activity. Fall in the activity was observed on the introduction of substituent at the 2-position of the quinazoline ring. The 3 substituted 4 (3H)-quinazolinimines generally exhibited weak activity. Ca2+ sensitizing effect of the 4-substituted amino derivatives was also examined in chemically skinned fiber from papillary muscle of guinea pig. The alkylamino derivatives exhibited small sensitizing effect, while the benzylamino derivatives exhibited large effect. Among them, KF15232 (Ix) was found to have the most potent cardiotonic and Ca2+ sensitizing activities. PMID- 1893497 TI - Synthesis and antiestrogenic activity of the compounds related to the metabolites of (E)-4-[1-[4-[2-(dimethylamino)ethoxy]phenyl]- 2-(4-isopropylphenyl)-1 butenyl]phenyl monophosphate (TAT-59) [corrected]. AB - The metabolites of (E) [corrected]-4-[1-[4-[2-dimethylamino)ethoxy]phenyl]- 2-(4 isopropylphenyl)-1-butenyl]phenyl monophosphate, TAT-59, (1), a potent antitumor agent for hormone-dependent tumors, and derivatives of TAT-59 were synthesized to confirm its proposed structure. The structure and the Z-configuration of the metabolites (2a-8a) were confirmed by comparison with synthesized authentic compounds. All of the metabolites and the derivatives of TAT-59 were tested for a binding affinity toward estrogenic receptors in vitro and antiuterotrophic activity in vivo. Most of the metabolites possessed remarkable binding affinity toward estrogenic receptors as well as fairly good antiuterotrophic activity. PMID- 1893498 TI - Reduction of 2,3,5-trimethyl-6-(3-pyridylmethyl)-1,4-benzoquinone by PB-3c cells and biological activity of its hydroquinone. AB - 2,3,5-Trimethyl-6-(3-pyridylmethyl)-1,4-benzoquinone (CV-6504) has inhibitory activities on both thromboxane A2 synthase and 5-lipoxygenase as well as scavenging activity against active oxygen species. The latter two activities are closely related to the quinone moiety, which is reduced to a hydroquinone in the living body. Comparison of these two activities for both the quinone and hydroquinone showed that the hydroquinone form had superior activities. Concerning the reduction mechanism by PB-3c cells we can see that superoxide dismutase (SOD) has no influence on the rate of reduction, but dicumarol almost completely inhibits the reduction at a concentration greater than 1 x 10(-6) M. Therefore, it can be concluded that CV-6504 is reduced mainly by two electron donating enzymes without the intermediary of a semiquinone radical and that the resulting hydroquinone inhibits lipid peroxidation as well as 5-lipoxygenase activity. PMID- 1893499 TI - 1,5-Benzoxathiepin derivatives. III. Optical resolution of methyl (+/-)-cis-3 hydroxy-4-[3-(4-phenyl-1-piperazinyl)propyl]-3,4-dihydro- 2H-1,5-benzoxathiepin-4 carboxylate hydrochloride ((+/-)-CV-5197) with selective 5-hydroxytryptamine2(5 HT2)-antagonistic activity. AB - The selective 5-HT2-receptor antagonist, methyl (+/-)-cis-3-hydroxy-4-[3-(4 phenyl-1-piperazinyl)propyl]-3,4-dihydro-2H- 1,5-benzoxathiepin-4-carboxylate hydrochloride ((+/-)-CV-5197) was resolved in high optical purity using (R)-(-)- and (S)-(+)-1,1'-binaphthyl-2,2'-diyl hydrogen phosphates ((R)-(-)- and (S)-(+) BNP). The absolute configuration of (+)-CV-5197 was determined to be 3S,4R by X ray crystallographic analysis. In the binding assay, it was demonstrated that (+) CV-5197 was a more active isomer (IC50 = 23 nM +/- 6.3) for 5-HT2 receptor binding than the (-)-enantiomer (IC50 = 1600 nM +/- 82). (+)-CV-5197 completely inhibited the 5-HT-induced contraction of the isolated pig coronary artery at a concentration of 3 x 10(-7) M, whereas (-)-CV-5197 showed little antagonistic activity, even at 3 x 10(-4) M. Thus, the agreement between the results of the binding assays and the biological activities for the 3S,4R enantiomer of CV-5197 suggests that its physiological activity is probably exerted through 5-HT2 receptor antagonism. PMID- 1893500 TI - Detection and identification of loline and its analogues in horse urine. AB - Several kinds of loline-type alkaloids, norloline, loline, N-acetylnorloline, N acetylloline, N-formylnorloline, N-formylloline and N-methylloline were detected in the urine of race-horses. Furthermore, a new compound of the alkaloids, N senecioylnorloline, was also found and identified. These compounds were mainly identified by means of gas chromatography-mass spectrometry (GC-MS) and gas chromatography-fourier transform-infrared spectrometry (GC-FT-IR). A certain plant of Gramineae containing four kinds of loline-type alkaloids was found in a bale of hay used for the horse forage. The taxonomic feature of the plant was different from known plants containing loline-type alkaloids. The common fragmentation of loline-type alkaloids under electron ionization was briefly discussed. PMID- 1893501 TI - 20 beta-hydroxysteroid dehydrogenase of neonatal pig testis: reverse catalytic (oxidation) reaction. AB - Neonatal pig testicular 20 beta-hydroxysteroid dehydrogenase (20 beta-HSD) catalyzed the oxidation of 20 beta-hydroxysteroids, 17 alpha,20 beta dihydroxypregn-4-en-3-one and 20 beta-hydroxypregn-4-en-3-one in the presence of beta-nicotinamide adenine dinucleotide phosphate (beta-NADP+). The behavior of 20 beta-HSD activity toward the substrate of 17 alpha,20 beta-dihydroxypregn-4-en-3 one differed from the catalytic reaction for 20 beta-hydroxypregn-4-en-3-one. The enzyme could catalyze not only 20 beta-hydroxysteroids but also 20 alpha-hydroxy 5-ene steroids, 20 alpha-hydroxypregn-5-en-3 beta-ol and 17 alpha,20 alpha hydroxypregn-5-en-3 beta-ol with 22.1 and 8.7% of activity relative to 20 beta hydroxypregn-4-en-3-one, respectively. The enzyme preferentially required beta NADP+, and also utilized beta-nicotinamide adenine dinucleotide beta-NAD+ and beta-nicotinamide adenine dinucleotide 3'-phosphate (beta-3'-NADP+) nonspecifically as the cofactor. The optimum pH was observed at pH 7.5 with the substrate of 20 beta-hydroxypregn-4-en-3-one. The activation energies obtained from oxidation-reduction reactions of 20 beta-HSD for the substrate of 20 beta hydroxypregn-4-en-3-one, progesterone and 17 alpha-hydroxyprogesterone were estimated at 13.8, 27.0 and 20.0 kcal/mol, respectively. PMID- 1893502 TI - A simple method for estimating surfactant impurities in solvents and subphases used for monolayer studies. AB - It is important to assess levels of surface active impurities in solutions used for characterization of monomolecular films and for deposition of Langmuir Blodgett multilayers. Traditional surface pressure-area measurements lack sufficient sensitivity because of the extremely low surface pressures surfactants exhibit below the formation of a coherent film. In contrast, surface potential measurements at the gas-liquid interface increase in a surfactant-dependent manner in the gaseous-liquid expanded transition region. Using this property of such films together with area reduction, levels of impurities representing less than or equal to 0.1% of a typical coherent monolayer can be quantitated. The measurement does not require ultrapure reference materials and can be performed on a solution immediately before spreading and compression of an experimental monolayer film. PMID- 1893503 TI - Leprosy control through multidrug therapy (MDT). AB - Multidrug therapy (MDT) is a major advance in leprosy control and has raised hopes among patients, health workers, and programme managers alike. Where its implementation is vigorous and sustained, the results are extremely gratifying; but problems, both technical and operational, need to be constantly reviewed and solutions found. The opportunities to markedly reduce leprosy in the next decade are immense, but it remains to be seen whether these opportunities are utilized so that leprosy will ultimately be eliminated as a public health problem. PMID- 1893504 TI - Adverse reactions to sulfa drugs: implications for malaria chemotherapy. AB - National adverse drug reaction registers in Sweden and the United Kingdom provided data on the type, severity and frequency of reported adverse reactions attributed to sulfa drugs. Reactions to the ten principal drugs were examined in terms of their half-lives and usual indications for use. Of 8339 reactions reported between 1968 and 1988, 1272 (15%) were blood dyscrasias, 3737 (45%) were skin disorders, and 578 (7%) involved the liver. These side-effects occurred with all types of sulfa drugs investigated, although at different relative rates, and 3525 (42%) of them were classified as serious. The overall case fatality rate (CFR) was 1:15 serious reactions, and was highest in patients with white blood cell dyscrasias (1:7). Drugs with longer elimination half-lives had higher CFRs, particularly for fatalities after skin reactions. In Sweden, the estimated incidences of serious reactions were between 9 and 33 per 100,000 short-term users of sulfa drugs (two weeks), between 53 and 111 among those on malaria prophylaxis, and between 1744 and 2031 in patients on continuous therapy. For dapsone, the incidence appeared to increase with higher doses. Our results indicate that sulfa drugs with short elimination half-lives deserve to be considered for use in combination with proguanil or chlorproguanil for malaria chemotherapy and possibly prophylaxis. The smaller risk of adverse reactions associated with lower-dose dapsone suggests that it should also be evaluated as a potentially safe alternative. PMID- 1893505 TI - Bacterial indicators of risk of diarrhoeal disease from drinking-water in the Philippines. AB - Inadequate measures of water quality have been used in many studies of the health effects associated with water supplies in developing countries. The present 1 year epidemiological-microbiological study evaluated four bacterial indicators of tropical drinking-water quality (faecal coliforms, Escherichia coli, enterococci and faecal streptococci) and their relationship to the prevalence of diarrhoeal disease in a population of 690 under-2-year-olds in Cebu, Philippines. E. coli and enterococci were better predictors than faecal coliforms of the risk of waterborne diarrhoeal disease. Methods to enumerate E. coli and enterococci were less subject to interference from the thermotolerant, non-faecal organisms that are indigenous to tropical waters. Little difference was observed between the illness rates of children drinking good quality water (less than 1 E. coli per 100 ml) and those drinking moderately contaminated water (2-100 E. coli per 100 ml). Children drinking water with greater than 1000 E. coli per 100 ml had significantly higher rates of diarrhoeal disease than those drinking less contaminated water. This threshold effect suggests that in developing countries where the quality of drinking-water is good or moderate other transmission routes of diarrhoeal disease may be more important; however, grossly contaminated water is a major source of exposure to faecal contamination and diarrhoeal pathogens. PMID- 1893507 TI - Demands on tertiary care for cardiovascular diseases in India: analysis of data for 1960-89. AB - Data on 43,544 consecutive patients with cardiac disorders admitted to one hospital were analysed under four etiological groups to study the changing trend in the demand for tertiary care between 1960 and 1989. While rheumatic fever went down in frequency, rheumatic valvular disease remained at an average of 40% of total cardiac admissions, coronary heart disease steadily increased from 4% in 1960 to about 33% in 1989, and congenital heart cases accounted for 24% of cardiac admissions. While other etiological groups have varied, coronary heart disease has shown an almost linear increase. The demand for cardiac surgery also has risen almost linearly. The implications of these findings on the health needs and health planning in the whole country pose a great challenge to planners. PMID- 1893508 TI - How long after being collected can blood still be cultured for chromosomal studies in the tropics. AB - To examine how long after their collection samples of peripheral blood could be successfully cultured for cytogenetic analysis in tropical countries, we determined the mitotic index in cultures of blood stored for up to 7 days in summer and winter. The results indicate that chromosomal analysis is successful if blood is stored for up to 2 days in summer or for up to 4 days in winter before initiating culture. Storing the blood in tissue culture medium rather than in heparin solution did not significantly improve the mitotic index. PMID- 1893506 TI - Behavioural risk factors for acquisition of HIV infection and knowledge about AIDS among male professional blood donors in Delhi. AB - In 1989-90 a study was carried out in Delhi of the risk behaviours and epidemiological characteristics exhibited by 15 paid blood donors who were positive for human immunodeficiency (HIV) virus and on 100 paid seronegative donors. All the donors were male. Compared with the seronegative donors, a significantly greater proportion of seropositive donors were unmarried, had lived in at least two cities in the previous 5 years, donated blood at least once per month, were heterosexually promiscuous, and had visited a clinic for sexually transmitted diseases. Awareness about acquired immunodeficiency syndrome (AIDS) was poor, and even those donors who had heard of AIDS were ignorant about certain important aspects. The results indicate that, based on the risk factors identified in this study, there is a need to adopt more careful selection criteria for blood donors in India. PMID- 1893509 TI - Increase in mortality associated with blindness in rural Africa. AB - Forty-seven persons were identified with visual impairment (visual acuity of 6/60 or less in their better eye) during a population-based survey in 1986 of eye disease in three villages in central Tanzania. Four years later, 41 (87%) of them and 70 (82%) of 84 age-, sex-, and village-matched controls with normal functional vision (visual acuity 6/18 or better in the better eye) were traced, and those who were still alive were re-examined. The remainder were reported to be alive but had moved to other villages. Deaths among those aged 40-79 years amounted to 10 among the 37 visually impaired and 7 among the 70 sighted controls. This gave an excess mortality rate (odds ratio) of 3.33 times (1.03 11.04, 95% Cl) among the visually impaired compared to their age-matched controls. The excess mortality rate for visually impaired women was 4.11 (0.72 25.5) and 2.71 (0.50-15.2) for visually impaired men. Nine out of 25 with vision of less than 3/60 in their better eye had died. The higher mortality rate among the visually impaired suggests that, in this environment, blindness is not only associated with considerable disability but is also associated with a shortened life expectancy, especially for women. PMID- 1893510 TI - Oral health manpower projection methods and their implications for developing countries: the case of Zimbabwe. AB - Manpower projections for oral health are generally held to be more accurate than those for other health sectors since the diseases involved and their treatment times can be predicted more precisely. Nevertheless most oral health manpower projections are either overestimates or are not in line with the resources of individual countries, especially in developing countries. Zimbabwe was taken as the study case, and oral health manpower projections were made using two of the most commonly employed methods and one new approach. The projections obtained using the three methods were all different, and even the lowest projection is beyond the resources of the country. It is recommended that in making oral health manpower projections, the facilities available to accommodate these personnel should also be taken into account. PMID- 1893511 TI - Endemic goitre in Guinea-Bissau. AB - A survey was performed of endemic goitre in the Oio, Gabu, and Cacheu regions of Guinea-Bissau. Among adult women, the following prevalences of goitre were observed: 53% (Oio), 48% (Gabu), and 27% (Cacheu). For goitres of grades 2 and 3 only, the prevalences were 20% (Oio), 13% (Gabu), and 2% (Cacheu). No cretinism or cases of thyroid dysfunction were found. The mean urinary iodine excretions in Oio, Gabu, and Cacheu were 17 micrograms/g, 24 micrograms/g and 33 micrograms/g creatinine, respectively. PMID- 1893512 TI - Pricing, distribution, and use of antimalarial drugs. AB - Prices of new antimalarial drugs are targeted at the "travellers' market" in developed countries, which makes them unaffordable in malaria-endemic countries where the per capita annual drug expenditures are US$ 5 or less. Antimalarials are distributed through a variety of channels in both public and private sectors, the official malaria control programmes accounting for 25-30% of chloroquine distribution. The unofficial drug sellers in markets, streets, and village shops account for as much as half of antimalarials distributed in many developing countries. Use of antimalarials through the health services is often poor; drug shortages are common and overprescription and overuse of injections are significant problems. Anxiety over drug costs may prevent patients from getting the necessary treatment for malaria, especially because of the seasonal appearance of this disease when people's cash reserves are very low. The high costs may lead them to unofficial sources, which will sell a single tablet instead of a complete course of treatment, and subsequently to increased, often irrational demand for more drugs and more injections. Increasingly people are resorting to self-medication for malaria, which may cause delays in seeking proper treatment in cases of failure, especially in areas where chloroquine resistance has increased rapidly. Self-medication is now widespread, and measures to restrict the illicit sale of drugs have been unsuccessful. The "unofficial" channels thus represent an unacknowledged extension of the health services in many countries; suggestions are advanced to encourage better self-medication by increasing the knowledge base among the population at large (mothers, schoolchildren, market sellers, and shopkeepers), with an emphasis on correct dosing and on the importance of seeking further treatment without delay, if necessary. PMID- 1893513 TI - Kinetics and cofactor requirements for the nitroreductive metabolism of 1 nitropyrene and 3-nitrofluoranthene by rabbit liver aldehyde oxidase. AB - Nitrated polycyclic aromatic hydrocarbons are environmental pollutants that have been shown to arise from a variety of sources, including diesel exhaust emissions and urban air. Most of these compounds are mutagenic in in vitro tests, and several have been shown to be carcinogenic in animals. We have investigated the kinetics of the metabolism of two of these compounds, 1-nitropyrene and 3 nitrofluoranthene, using rabbit liver aldehyde oxidase, an enzyme that has been shown to catalyze the bioactivation of 1-nitropyrene. The nitro-reduction of 20 microM [4,5,9,10-3H]1-nitropyrene or 20 microM [4-3H]3-nitrofluoranthene by aldehyde oxidase required the presence of flavin mononucleotide (FMN) or flavin adenine dinucleotide (FAD), and was inhibited by oxygen in a concentration dependent manner. In contrast, the aldehyde oxidase oxidation of the electron donor 1-methylnicotinamide did not require FMN or FAD, indicating that the aldehyde oxidase was not isolated as an apoenzyme. The aldehyde oxidase Km and Vmax for 1-nitropyrene were 4.2 microM and 16.3 pmol/min/unit enzyme, while the respective values for 3-nitrofluoranthene nitroreduction were 1.9 microM and 5.4 pmol/min/unit enzyme. The requirement for flavins in the nitroreduction of 1 nitropyrene and 3-nitrofluoranthene suggests that reduced free flavins may be required in cytosolic nitroreduction of 1-nitropyrene and 3-nitrofluoranthene. More importantly, the inhibition of nitroreduction by concentrations of oxygen that are representative of intracellular concentrations strongly suggests that the reasons for the apparent lack of 1-nitropyrene nitroreduction in vivo may be due to oxygen-mediated oxidation of a reduced metabolite of 1-nitropyrene. PMID- 1893514 TI - A proposed role for silicates and protein in the proliferative effects of saccharin on the male rat urothelium. AB - High doses of sodium saccharin, a non-genotoxic chemical, lead to the formation of silicate-containing precipitate and microcrystals in urine of male rats. Differences in urinary protein, pH, sodium and other factors affect silicate containing precipitate and microcrystal formation as well as the bladder effects of sodium saccharin. Total urinary silicon concentration (mostly soluble) in sodium saccharin-fed rats is similar to or lower than the concentration in control rats. Binding of saccharin to male rat urinary proteins was demonstrated by equilibrium-gel filtration. We propose that by binding to urinary proteins under appropriate conditions, saccharin produces a nidus for the formation of silicate-containing precipitate and crystals. These appear to be cytotoxic to the superficial bladder epithelium, with cell death resulting in regenerative hyperplasia. Factors that influence the formation of these silicate-containing materials might provide a rationale for sex, species, dose and dietary differences in response to sodium saccharin. PMID- 1893515 TI - Hepatocellular DNA synthesis in rats given peroxisome proliferating agents: comparison of WY-14,643 to clofibric acid, nafenopin and LY171883. AB - The mitogenic effects of peroxisome proliferating agents have been implicated in their carcinogenicity. WY-14,643 stimulates an increase in hepatocellular DNA replication that persists with continued administration, but it is unclear if other peroxisome proliferators share this property. In these studies, WY-14,643 was compared to clofibric acid, nafenopin and LY171883 given to rats in the diet for up to 30 days. DNA replication in the rat liver was quantified by immunohistochemical methods after continuous s.c. infusion of bromodeoxyuridine by osmotic minipump. During the first 7 days of treatment, WY-14,643 (0.1% in diet) and nafenopin (0.05%) increased the percentage of bromodeoxyuridine-labeled hepatocytes to greater than 50%, from 3% in controls. Clofibric acid (0.5%) and LY171883 (0.3%) increased the labeling to approximately 33%. The replicative response to each of the compounds was localized primarily to the periportal region of the liver lobule. The time-course of replication induced by clofibric acid and WY-14,64.3 was examined over 3 day intervals. The peak of replication in response to clofibric acid occurred during days 4-6, whereas the effect of WY 14,643 peaked during days 1-3 and was much greater than clofibric acid. The replicative response to WY-14,643 persisted through 30 days at dietary concentrations of 0.1 and 0.005%. Nafenopin, LY171883 and clofibric acid were without effect on DNA replication on days 28-30 even though the hepatomegaly and induction of peroxisomal beta-oxidation persisted. Thus, under the conditions of these experiments, the persistent replicative effect through 30 days was unique to WY-14,643. Although sustained replication in the general population of hepatocytes may be involved in the carcinogenesis of WY-14,643, it does not appear to be a factor in the hepatocarcinogenesis of the other peroxisome proliferators. PMID- 1893516 TI - Toxicokinetics of tumour promoters of mouse skin. II. Metabolism of the tumour promoter 12-O-tetradecanoylphorbol-13-acetate in mouse skin and biological activities of metabolites. AB - The metabolism of the phorbol diester [20-3H]12-O-tetradecanoylphorbol-13-acetate [( 3H]TPA) was studied in the back skin of NMRI mice after topical administration of a single tumour-promoting dose, dp. Up to 72 h after administration most of the radioactivity recovered from the skin surface, and from the epidermis and dermis of the treated skin area was unchanged TPA, as determined by silica gel HPLC of extracts obtained from these skin fractions. The major TPA metabolite was less polar than TPA and chromatographed in the range of long-chain TPA-20 acylates. At 72 h, it accounted for about 25, 5 and 30% of total radio-activity extracted from skin surface, epidermis and dermis respectively. Of metabolites more polar than TPA, phorbol-13-acetate (PA) by far predominated over 12-O tetradecanoylphorbol (TP) in both the epidermis and dermis, and by 72 h its relative amount was 3.9 and 2.4% in these skin fractions. Both phorbol monoesters, PA and TP, were not detected in skin surface extracts. In addition to metabolites, various autoxidation products of TPA were present in small amounts in the extracts from each of the skin fractions. The TPA-20-acylate fraction of metabolites isolated from the extracts of skin fractions at 24 h was separated further into the individual metabolites by the combined use of argentation and reversed-phase HPLC. These individual metabolites were identified by co chromatography with authentic reference compounds. They were TPA-20-acylates carrying saturated fatty acids (16-26 carbon atoms), cis-mono-unsaturated fatty acids (16-24 carbon atoms), linoleic acid and arachidonic acid. The conjugation of TPA with long-chain fatty acids is the first example of a new route of xenobiotic metabolism in skin. When tested for irritant activity on the mouse ear, TPA-20-acylates were about one to two orders of magnitude less active than TPA. Similarly, when TPA-20-tetradecanoate was tested for tumour-promoting activity on the back skin of NMRI mice over a dose range of dp = 50-200 nmol applied twice weekly according to the computer-assisted standard protocol 16, it was found to be of only intermediate potency as compared to the highly potent tumour promoter TPA. The results of the present investigation indicate that metabolic conjugation of TPA with long-chain fatty acids to yield TPA-20-acylates is another pathway of metabolic deactivation of TPA, thus supporting the hypothesis that TPA itself is the ultimate tumour promoter in mouse skin. PMID- 1893517 TI - Effects of dietary indole-3-carbinol on estradiol metabolism and spontaneous mammary tumors in mice. AB - Indole-3-carbinol (I3C) is a potent inducer of cytochrome P450 enzymes in many species, including humans. We therefore studied alterations in the cytochrome P450-dependent metabolism of estradiol in different strains of mice consuming I3C in semisynthetic powdered diets at doses ranging from 250 to 5000 p.p.m. (34-700 mg/kg/day) for different periods of time. In short-term metabolic studies (3 weeks), wet liver weight increased in SW and C3H/OuJ mice in a dose-responsive manner. Dietary I3C increased the cytochrome P450 content measured in hepatic microsomes, as well as the extent of estradiol 2-hydroxylation, up to 5-fold. In a long-term feeding experiment (8 months), female C3H/OuJ mice consumed synthetic diets containing I3C at 0, 500 or 2000 p.p.m. Mammary tumor incidence and multiplicity were significantly lower at both doses of I3C, and tumor latency was prolonged in the high-dose group. We conclude that I3C is an inducer of hepatic P450-dependent estrogen metabolism in mice, and that it is chemopreventive in the C3H/OuJ mouse mammary tumor model. This protective effect may be mediated in part by the increased 2-hydroxylation and consequent inactivation of endogenous estrogens. PMID- 1893518 TI - Proliferation of carcinogen-damaged hepatocytes during cell-cycle-dependent initiation of hepatocarcinogenesis in the rat. AB - Hepatocyte proliferation and damage to DNA were characterized during the initiation phase of carcinogenesis in livers of rats that had received a single administration of the methylating agent methyl(acetoxymethyl)nitrosamine (DMN OAc). Quiescent non-proliferating hepatocytes in intact livers did not appear to be susceptible to initiation by DMN-OAc, whereas proliferating hepatocytes in the S phase appeared to have greatest risk. To characterize the phenomenology of S phase-dependent initiation further, the fractions of hepatocytes in the S and M phases of the cell cycle were enumerated at various times after treatment with DMN-OAc. Hepatocytes treated when in G1 experienced a delay of up to 20 h in the onset of S phase and a reduced rate of entry into the S and M cycle phases. Hepatocytes treated when in S phase experienced considerable delay in progression to mitosis due to part to inhibition of DNA replication. Hepatocytes treated when in late S/G2 also demonstrated a delay in progression into mitosis. The levels of 7-methylguanine and O6-methyldeoxyguanosine were quantified in the nuclear DNA of proliferating hepatocytes. The kinetics of removal of these lesions appeared to be first-order (half-life = 24 h). Hepatocyte risk of initiation was modeled by a function which summed over time the product of the fraction of hepatocytes in the S phase and the fraction of residual, unrepaired damage to DNA. For hepatocytes treated when in early G1, the time-weighted frequency of premutagenic DNA damage that was present during DNA replication was estimated to be less than half of that for hepatocytes treated when in early S. The results suggest that cell-cycle dependent variation in sensitivity to initiation of hepatocarcinogenesis may be, in part, due to efficient removal of potentially carcinogenic lesions from DNA during an extended G1. The apparent high sensitivity of hepatocytes in late S/G2 suggests the contribution of additional factors. PMID- 1893519 TI - Endogenous formation of N-nitrosamines from piperazine and their urinary excretion following antihelmintic treatment with piperazine citrate. AB - Antihelmintic treatment with piperazine (1,4-diazacyclohexane) for microfilarie parasitism results in the endogenous formation of piperazine-derived N nitrosamines. The urinary excretion of these N-nitrosamines was determined by biochemical monitoring of 14 patients receiving 2 g piperazine citrate. The urinary excretion (mean +/- SD) of N-mononitrosopiperazine (MNPz) was 27.0 +/- 26.7 micrograms/day (range 0.6-96.0 micrograms/day). Trace levels of 0.73 +/- 0.92 micrograms/day N,N'-dinitrosopiperazine (DNPz) (range ND-2.8 micrograms/day) were also found in 7 of 14 urine samples. N-Nitroso-3-hydroxypyrrolidine (NHPYR), a metabolite of both MNPz and DNPz, was detected in 11 of 14 urine samples at a mean concentration of 1.74 +/- 1.72 micrograms/day (range ND-5.7 micrograms/day) and traces of N-nitrosodiethanolamine in two samples at levels of 0.3 and less than 0.1 micrograms/day. The results show that biochemical monitoring of urinary NHPYR may be a good indicator of endogenous MNPz formation. While DNPz was also detected in urine, conclusive validation for its endogenous formation could not be provided because no evidence was found for the presence of its major metabolite, N-nitroso-(2-hydroxyethyl)glycine in urine. PMID- 1893520 TI - The benzamide derivative metoclopramide causes DNA damage and inhibition of DNA repair in human peripheral mononuclear leukocytes at clinically relevant doses. AB - The polysubstituted benzamide derivative metoclopramide (MCA) has previously been shown to enhance the effect of cisplatin and ionizing radiation treatment of xenografted human squamous cell carcinomas from the head and neck region. In the present work we show that MCA decreases the nucleoid sedimentation rate, indicating that MCA causes strand breaks in the DNA of human peripheral mononuclear leukocytes treated in vitro. This effect is seen with MCA in the dose range from 100 nM to 1 mM. MCA also stimulated the activity of the enzyme adenosine-diphospho-ribosyl transferase both in cells treated with MCA alone, and in combination with 15 Gy. This was taken as additional evidence that MCA causes DNA strand breaks. The DNA damage induced by MCA was poorly repaired when assessed by nucleoid sedimentation analysis, and this effect on repair was confirmed by showing that MCA also inhibits N-acetoxy-2-acetylaminofluorene induced unscheduled DNA synthesis. The effect of MCA on DNA damage measured by nucleoid sedimentation has also been demonstrated in permeabilized cells. These data indicate that the DNA-damaging effect of MCA is not dependent on surface receptors or cytoplasmic processes. PMID- 1893521 TI - The modification of guanine nucleosides and nucleotides by the borderline arylamine carcinogens 4-methyl- and 4-methoxyaniline: chemistry and structural characterization. AB - We report here on the conformational analysis of C8-arylamine nucleoside and nucleotide adducts of the borderline carcinogens 4-methylaniline and 4 methoxyaniline. The non-phosphorylated adducts show anti conformation of the glycosidic link, while the corresponding 5'-phosphorylated adducts have a syn conformation. All adducts exhibit a predominant C2'-endo conformation of the sugar ring and a gg conformation of the exocyclic bond. PMID- 1893522 TI - Accurate in vitro translesion synthesis by Escherichia coli DNA polymerase I (large fragment) on a site-specific, aminofluorene-modified oligonucleotide. AB - We have measured the accuracy of in vitro synthesis by DNA polymerase I (large fragment) during translesion synthesis past an aminofluorene (AF) adduct. These studies were carried out using a site-specifically modified template which contained a single AF adduct. The template was prepared by first modifying the lone guanine in a 17 base long oligonucleotide and extensively purifying and characterizing this product. The modified 17mer was then ligated to a synthetic duplex to produce a 31 nucleotide long template strand containing the AF adduct annealed to a 14mer, such that the 3'-hydroxyl primer terminus was four nucleotides before the modified guanine. Synthesis on this template by DNA polymerase I efficiently bypassed the AF adduct and produced full-length duplex 31mers. T7 DNA polymerase, on the other hand, was unable to utilize the AF modified template though it was active on an identical unmodified one. The strand synthesized by DNA polymerase I was then separated from the modified strand, annealed to a complementary oligonucleotide, and the resulting heteroduplex cloned into M13. Each of the 49 clones isolated had sequences which indicated that cytidine had been incorporated opposite the AF-modified guanine. PMID- 1893523 TI - Synthesis of a novel fluorinated benzo[a]pyrene: 4,5-difluorobenzo[a]pyrene. AB - The synthesis of 4,5-difluorobenzo[a]pyrene, as a fluorinated probe to investigate the involvement of the K-region in the further metabolic activation of benzo[a]pyrene metabolites, is described. Benzo[a]pyrene-4,5-dione obtained from 2,3-dichloro-5,6-dicyano-1,4-benzoquinone oxidation of cis-4,5-dihydro-4,5 dihydroxybenzo[a]pyrene was fluorinated with dimethylaminosulfur trifluoride to give 4H,5H,4,4,5,5,-tetra-fluorobenzo[a]pyrene. Defluorination using lithium aluminum hydride in tetrahydrofuran gave 4,5,-difluorobenzo[a]pyrene. PMID- 1893524 TI - Changes in inositol phosphate metabolism are associated with terminal differentiation and neoplasia in mouse keratinocytes. AB - Cultured murine keratinocytes respond to specific Ca2+ levels in medium (Ca0) by expressing markers of terminal differentiation. A Ca0 of 0.05 mM selects for a basal cell phenotype, whereas spinous cell characteristics occur in 0.12 mM Ca2+ and cornified envelopes develop in 1.0 mM Ca2+. An increase in inositol phosphate (InsP) metabolism is associated with higher Ca2+ in the medium. The magnitude of Ca(2+)-stimulated InsP turnover is Ca0-dependent, whereas Ca0 of 0.05, 0.12 or 1.4 mM resulted in a graded, sustained (greater than 24 h) increase in InsPs. Diacylglycerol (DAG) levels similarly increased in a graded manner. The major inositol trisphosphate (InsP3) to accumulate was Ins-1,3,4-P3 while Ins-1,4,5-P3 increased transiently. Neoplastic keratinocyte cell lines, 308 and SP-1, which produce benign tumors and have a mutated c-rasHa gene, do not express markers of differentiation in response to Ca2+. Basal InsP and DAG are 2- and 5-fold higher respectively in the neoplastic cells relative to normal keratinocytes. However, the metabolic profiles of InsPs were similar in normal and neoplastic cells. In neoplastic cells, InsP metabolism was stimulated even further following a Ca2+ increase, and this was graded to the Ca0. The unusual, sustained Ca(2+)-graded InsP response in normal cells is consistent with the turnover of InsP contributing to the signals controlling expression of markers of differentiation. Very high InsP turnover and DAG levels, as in neoplastic cells, may be inhibitory to marker expression. PMID- 1893525 TI - DNA polymerase-mediated nucleotide incorporation adjacent to hydrocarbon deoxyadenosine and hydrocarbon-deoxyguanosine adducts. AB - To examine the effect of DNA adducts on nucleotide incorporation by DNA polymerase at 3' neighboring bases, synthetic oligonucleotides (16mers) containing a purine at position 13 from the 3' end and any one of the four possible bases at position 12 were prepared and reacted with 7 bromomethylbenz[a]anthracene. Using HPLC, unmodified oligonucleotide was separated from oligonucleotide containing a single adduct, at either an adenine or a guanine residue. These products were annealed with a 32P 5'-end labeled primer (11mer) and incubated with modified T7 DNA polymerase (Sequence, version 2.0) in the presence of deoxyribonucleoside 5'-triphosphates. Analysis by gel electrophoresis showed that unmodified oligonucleotide template allowed the primer to be rapidly extended to the entire length of the template. However, the presence of an adduct caused primer extension to stop at the base 3' to the adduct. While correct base pairing occurred at this termination site with most adducted templates, there was a high frequency of misincorporation of guanine opposite a thymine located 3' to an adenine adduct. This result suggest that some bulky carcinogen--DNA adducts may lead to base mismatches at neighboring bases. PMID- 1893526 TI - Comparative DNA binding of polynuclear aromatic hydrocarbons and their dihydrodiol and bay region diolepoxide metabolites in newborn mouse lung and liver. AB - Bay region diolepoxides of polynuclear aromatic hydrocarbons (PAHs) generally are more tumorigenic than their parent PAHs in newborn mice. This contrasts to the results obtained in mouse skin, in which the same diolepoxides are frequently less tumorigenic than their parents. In order to evaluate mechanism(s) responsible for this behavior we have investigated the binding of metabolites of [3H]benzo[a]pyrene (B[a]), [3H]5- and [3H6]6-methyl-chrysene (5-MeC and 6-MeC) and their corresponding dihydrodiols and bay region diolepoxides to pulmonary and hepatic DNA in male and female newborn mice and compared the results with their tumorigenic activities. Groups of 1 day old mice were treated with 0.4 or 4 nmol of the appropriate compounds in DMSO by i.p. injection. HPLC analysis of DNA hydrolysates obtained 24 h after treatment indicated that levels of diolepoxide DNA adducts following treatment with (+-)-[3H]7,8-dihydroxy-7,8-dihydroB[a]P and (+-)-[3H]anti-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydroB[a] P are 5- and 10 fold higher than those formed from [3H]B[a]P. The major products (70-80%) released upon enzymatic hydrolysis of DNA following treatment with [3H]B[a]P, [3H]5-MeC and [3H]6-MeC were unidentified polar compounds. Levels of these unknown products were lower and formation of diolepoxide--DNA adducts higher when test compounds were changed from parent PAHs to the corresponding dihydrodiols and diolepoxides. Comparison of these results with those of tumorigenesis studies indicates a correlation between formation of B[a]P-diolepoxide--DNA adducts and induction of tumors in newborn mouse lung, but not in liver. These observations are consistent with the high sensitivity of the newborn mouse lung towards the tumorigenic effects of bay region diolepoxides. Previous studies have demonstrated that 1R,2S-dihydroxy-3S,4R,epoxy, 1,2,3,4-tetrahydro-5-MeC (5-MeC 1R,2S-diol-3S,4R-epoxide) is a potent lung tumorigen while the corresponding diol epoxide of 6-MeC had no effect in newborn mice. From the results of the present study, we estimate that at equimolar doses the formation of diolepoxide--DNA adducts from 5-MeC-1R,2S-diol-3S,4R-epoxide would be at least 20-fold greater than from the corresponding diolepoxide of 6-MeC in newborn mouse lung. Thus, the higher tumorigenic activity of 5-MeC-1R,2S-diol-3S,4R-epoxide compared to that of the corresponding diol epoxide of 6-MeC is partially due to its greater extent of DNA damage. PMID- 1893527 TI - Production of antibodies to peptide sequences present in human O6-alkylguanine DNA alkyltransferase and their use to detect this protein in cell extracts. AB - Antisera were raised in rabbits to three peptides which correspond to sequences of amino acids present in human O6-alkylguanine-DNA alkyltransferase (residues 1 11, 8-20 and 197-207). These antisera recognized the alkyltransferase protein on Western blots of proteins from a number of Mer+ human tumor cell lines but this protein was found to be absent from Mer- tumor cell lines. The alkyltransferase protein was also detected by these antisera in some extracts from human liver samples but other human liver extracts having a high alkyltransferase activity failed to react with antibodies directed towards the carboxyl terminus of the protein, suggesting that part of this region can be removed by protease action without loss of activity or that there is genetic variability in this region. This result indicates that studies with a number of antisera or with an antibody known to be directed towards an essential, invariant region of the alkyltransferase will be needed for unequivocal detection of the alkyltransferase by antibody screening. The immunoreactive human alkyltransferase protein was absent from CHO cell lines that had previously been selected for alkyltransferase expression after transfection with human DNA. It is therefore probable that the hamster gene has been reactivated in these cells. PMID- 1893528 TI - Use of antibodies to human O6-alkylguanine-DNA alkyltransferase to study the content of this protein in cells treated with O6-benzylguanine or N-methyl-N' nitro-N-nitrosoguanidine. AB - Antisera raised in rabbits to three peptides corresponding to amino acid sequences found in human O6-alkylguanine-DNA alkyltransferase were used to study the fate of the alkyltransferase protein in human colon tumor cells after exposure to N-methyl-N'-nitro-N-nitrosoguanidine or to O6-benzylguanidine. Under these conditions, the alkyltransferase protein becomes inactivated, presumably by the conversion of its cysteine acceptor site to S-methylcysteine or S benzylcysteine respectively. It was found that the protein was rapidly degraded after such inactivation both in intact cells and in cell-free extracts. It is probable that a conformational change in the protein is brought about by conversion of the alkyltransferase to the inactive form by alkylation of the cysteine acceptor site. This change may render the protein very sensitive to proteolytic degradation. The rapid degradation of the inactive form of the protein may serve as a signal for its resynthesis but in the short term ensures that its reactivation by regeneration of the cysteine acceptor site is unlikely to occur to any significant extent. The short half-life of the inactivated alkyltransferase protein makes it probable that measurement of the content of the alkyltransferase protein by immunohistochemistry, which is likely to measure the sum of the active and inactivated forms of the protein, will nevertheless yield an accurate estimation of the cellular capacity to repair O6-methylguanine provided that procedures with sufficient specificity and affinity can be developed. PMID- 1893529 TI - Improvement in the diagnostic potential of 32P-postlabeling analysis demonstrated by the selective formation and comparative analysis of nitrated-PAH-derived adducts arising from diesel particle extracts. AB - Two versions of the 32P-postlabeling assay (nuclease P1 and butanol extraction) enhance the detection limit of polycyclic aromatic hydrocarbon (PAH)-modified DNA. Previously published studies suggest that DNA adducts derived from N substituted aryl compounds are poorly recovered in the nuclease P1 version. In this study, both versions were employed to ascertain whether the apparent differences in sensitivity could be used to select diagnostically for nitroaromatic-DNA adducts derived by treating calf thymus DNA with organic extracts isolated from four diesel and one gasoline vehicle emission particles. We enhanced the formation of nitrated-PAH-derived adducts through xanthine oxidase (XO)-catalyzed nitroreduction of nitrated-PAHs, constituents previously detected in the diesel emissions. Chromatographic mobilities of the XO-derived DNA adducts were compared to adducts detected in calf thymus DNA resulting from rat liver S9-mediated metabolism. All four diesel organic extracts treated with XO resulted in the formation of one major DNA adduct, chromatographically distinct from the multiple DNA adducts detected in the rat liver S9-treated incubations. This adduct was detectable with the butanol extraction but not the nuclease P1 version of the 32P-postlabeling assay and was chromatographically similar to DNA adducts formed following XO nitroreduction of 1-nitropyrene or ascorbic acid treatment of 1-nitro-8-nitroso-pyrene and 1-nitro-6-nitrosopyrene. In contrast, when S9 activation was used, multiple DNA adducts were detected along a diagonal zone of radioactivity and were radioactively labeled with equivalent efficiency irrespective of the assay version employed. The in vitro calf thymus DNA model described in this study enhances the diagnostic potential of the 32P-postlabeling assay through the selective formation of nuclease P1 sensitive N-substituted aryl-derived DNA adducts. PMID- 1893530 TI - Rotation about the C6-O6 bond in O6-methylguanine: the syn and anti conformers can be of similar energies in duplex DNA as estimated by molecular modeling techniques. AB - O6-Methylguanine (O6MeGua) is generally regarded as the most important premutagenic lesion formed from carcinogenic methylating agents, so its structure and mechanism of action have received considerable attention. Two conformations for the methyl group in O6MeGua are possible: in one the methyl group is syn with respect to the N(1)-position of the purine, points into the helix, and disrupts hydrogen bonding potential; in the second the methyl group is anti with respect to the N1-position of the purine, and points into the major groove. Syn-O6MeGua has been observed when paired with thymine in duplex DNA as determined by NMR, while anti-O6MeGua has been observed when paired with thymine in X-ray diffraction studies. Herein, molecular modeling/computational chemistry is used to evaluate this apparent discrepancy. [N6-Methyladenine (N6MeAde) was also studied, because it is isoelectronic with O6MeGua, and because more information is available about its energetics. Syn-N6MeAde is computed to be favored in small molecules; however, the fraction of the anti-conformer is computed to be approximately 7%, which agrees well with experimentally determined values (4 12%). In contrast, the anti conformation for N6MeAde is calculated to be favored in duplex DNA, which is consistent with what has been observed experimentally using both NMR and X-ray diffraction techniques. The agreement between the calculated and experimentally determined results with N6MeAde suggest that the methods are reasonable.] For O6MeGua, a syn/anti ratio of approximately 10(3) is computed for small molecules. In duplex DNA, syn-O6MeGua is computed to be favored, but the anti-conformer is less than approximately 1 kcal/mol higher in energy. Whether syn- or anti-O6MeGua predominates may depend upon sequence context, as well as environmental factors. The comparison between O6MeGua and N6MeAde suggests a rationale for the puzzling observation that O6MeGua appears to be a cytotoxic lesion in eukaryotic, but not prokaryotic, cells. PMID- 1893531 TI - Sequential changes of gap-junctional intercellular communications during multistage rat liver carcinogenesis: direct measurement of communication in vivo. AB - We have developed a simple method to measure gap-junctional intercellular communication (GJIC), by means of microinjection/dye transfer assay, in liver slices freshly removed from the rat. Using this method and immunostaining of connexin 32 (cx32), the major liver gap junction protein, we studied sequential changes of GJIC during chemical hepatocarcinogenesis in male Fischer-344 rats under a modified Solt-Farber protocol (3 weeks 4 day exposure regimen). Four weeks after commencement of the protocol, there was a substantial decrease in GJIC in the liver parenchyma, which was free from focal lesions. The decrease in GJIC persisted up to at least the 15th week of treatment, while a decrease in the number of immunoreactive cx32 spots was evident only at 4 weeks of post-protocol commencement. Most enzyme-altered (GST-P-positive) focal lesions showed markedly lower GJIC and a significantly lower number of cx32-positive spots than surrounding hepatocytes. Most GST-P-positive foci showed a selective lack of GJIC with surrounding heptocytes. Hepatocellular carcinomas arising 1 year after the carcinogenic regimen had significantly reduced communicational capacity accompanied by a large decrease in cx32 expression. These results suggest that a progressive decrease in homologous as well as heterologous GJIC in preneoplastic lesions occurs during rat hepatocarcinogenesis, and that preneoplastic lesions with the most prominent disorders in GJIC may be more likely to develop into carcinomas. PMID- 1893532 TI - Trichloroacetic acid: studies on uptake and effects on hepatic DNA and liver growth in mouse. AB - Trichloroacetic acid (TCA) was tested in mice for its ability to cause single strand breaks (SSBs) in hepatic DNA in the presence and absence of liver growth induction. Male B6C3F1 mice were given 1, 2 or 3 daily doses of TCA (500 mg/kg p.o.) as a neutralized solution (sodium salt) and killed 1 h after the final dose. Some mice were given a single dose of TCA (500 mg/kg p.o.) as the acid or as a neutralized solution and killed 24 h after. Liver nuclei were prepared and the induction of DNA SSBs assayed. TCA gave no significant response. Absorption and distribution studies were conducted with radiolabelled trichloro[2-14C]acetic acid, which was administered by gavage (500 mg/kg) as aqueous free acid, neutral aqueous solution (sodium salt) or free acid in corn oil. The absorption and distribution of TCA was similar in all cases: the chemical was absorbed rapidly after dosing, maximum plasma and liver concentrations of free radiolabel being achieved in less than 1 h. Within the first 4 h following dosing there was no evidence of binding to DNA or other macromolecules in plasma and very little 'covalent' binding was detected in liver, indicating that at times when maximum DNA single-strand breakage has been reported there was no significant binding to liver cells. Studies on liver growth parameters (hyperplasia and peroxisome proliferation) with TCA revealed that the chemical induced small but significant increases in both parameters. No SSB induction was detected in association with either liver growth phenomenon elicited by TCA. We have thus found no evidence that TCA causes SSBs in the hepatic DNA of treated mice, in contrast to previous observations by other investigators. PMID- 1893533 TI - Ascorbate is the principal reductant of chromium (VI) in rat liver and kidney ultrafiltrates. AB - Chromium (VI) reductase activity was measured in ultrafiltrates of rat liver and kidney after various pretreatments in vitro at 37 degrees C and pH 7.0. Preincubation of ultrafiltrates with L-ascorbate oxidase (EC 1.10.3.3), which specifically eliminated ascorbate, blocked approximately 80% of the Cr(VI) reductase activity. Heat-denatured ascorbate oxidase had no effect on Cr(VI) reductase activity in ultrafiltrates. Preincubation of ultrafiltrates with N ethylmaleimide, which non-specifically blocked sulfhydryls, including reduced glutathione, decreased Cr(VI) reductase activity by only 20%. Treatment of male Sprague-Dawley rats with phorone decreased non-protein sulfhydryl (NPSH) levels in rat liver by greater than 90% and tripled reduced ascorbate levels 2 h after treatment. Ultrafiltrates of liver prepared from phorone-treated rats had twice the Cr(VI) reductase activity of control ultrafiltrates, and greater than 95% of this activity could be blocked by preincubation with ascorbate oxidase. Treatment of rats with sodium dichromate (20 mg/kg) caused a significant decrease in ascorbate levels in kidney but not liver, and no change in NPSH levels in kidney or liver, 15 min after treatment. We conclude that ascorbate is the major reductant of Cr(VI) in rat liver and kidney ultrafiltrates and may well be the major non-enzymatic reductant of Cr(VI) in rat liver and kidney in vivo. PMID- 1893534 TI - Expression of O6-methylguanine-DNA methyltransferase in malignant human glioma cell lines. AB - When animals are treated with carcinogenic agents that alkylate O6-guanine residues, the incidence of tumors in specific tissues often relates inversely to the level of the DNA repair enzyme O6-methylguanine-DNA methyltransferase (MGMT) present in the tissue. Similarly, the hypersensitivity to anticancer chloroethylnitrosoureas of some human tumor cell lines is believed to result from their deficiency in MGMT. We have undertaken a comprehensive investigation of MGMT expression in a panel of nine characterized human glioma cell lines. Methyltransferase activity determined by incubating protein extracts of these glioma lines with [3H]methylated DNA ranged from undetectable in six lines (the Mer- phenotype) to greater than 0.8 pmol/mg in two lines (U-373 MG and D-392 MG). MGMT protein was undetectable in Western blots of the Mer- cell extracts probed with specific anti-MGMT monoclonal antibodies. Consistent with these results, steady-state levels of MGMT mRNA, determined by Northern blot analysis, were detectable only in the three Mer+ glioma lines (U-373 MG, D-392 MG, D-263 MG). Southern analysis of EcoRI-digested DNA probed with MGMT cDNA revealed no amplification, rearrangement or deletions of the MGMT gene in any of the glioma cell lines. This is the first report that examines MGMT expression at the biochemical, molecular and genetic levels in a particular tumor type. These studies suggest that transcriptional regulation is the basis of the Mer- phenotype in these malignant human glioma cell lines, since no gross structural or quantitative abnormalities of the MGMT gene were seen in the phenotypically Mer- lines. PMID- 1893535 TI - Nuclease S1-mediated enhancement of the 32P-postlabeling assay for aromatic carcinogen-DNA adducts. AB - Treatment of DNA digests with nuclease P1 prior to 32P-labeling of adducts has previously been shown to enhance the sensitivity of the 32P-postlabeling assay for the detection of aromatic carcinogen-DNA adducts. The enhancement was based on the ability of nuclease P1 to remove the 3'-phosphate from normal nucleotides but not the corresponding phosphate from most aromatic adducted nucleotides. We investigated the utility of another 3'-dephosphorylating enzyme, nuclease S1, for this purpose, and found it to be as effective as nuclease P1. The recovery of DNA adducts derived from benzo[a]-pyrene (B[a]P), benzoquinone (BQ) and 2 acetylaminofluorene (AAF) was comparable after enhancement with either enzyme. Some differences were, however, observed. Recovery of a minor B[a]P adduct was 1.5 times higher by the S1 procedure. Among minor adducts of BQ, two showed higher values (2.8- and 6.1-fold) by the S1 procedure and one by the P1 procedure (2.4-fold). The major AAF adduct, deoxyguanosine-C8-AF, exhibited poorer recovery (1-11%) by either procedure, while the minor adducts, deoxyguanosine-N2-AAF and deoxyguanosine-C8-AAF, showed better recovery (2-3 times) than by the enhancement procedure involving extraction of adducts into butanol. Our results show that the nuclease S1 assay can complement the nuclease P1 assay, with improved recoveries for some adducts. Considering the complexity of the postlabeling assay, this additional variant may prove useful in unequivocal detection of DNA adducts. PMID- 1893536 TI - Contact lenses after corneal lacerations. AB - Contact lenses were fit after traumatic corneal lacerations in 30 eyes (28 patients). Twenty-eight of the eyes (93%) were aphakic. Twenty-two of the 30 eyes (73%) wore the contact lens successfully (average follow-up 22 months). The visual acuity with the contact lens was 20/40 or better in 25 eyes (83%). In 13 eyes (43%) the final contact lens fit was a rigid gas permeable lens, with a daily wear soft contact lens as the final lens in 17 eyes (57%). The eight failures included four patients who were contact lens intolerant, two who had binocular diplopia, and two who lacked motivation. All but one of 12 (92%) small corneal lacerations (less than 3 mm) were successfully fit with contact lenses. Eleven out of the 13 (85%) central large lacerations, but none of the five large peripheral lacerations could be successfully fit with a contact lens. Three of the 30 eyes (10%) developed late retinal detachments. Contact lenses are successful in the majority of patients referred after corneal lacerations, but fitting these patients is challenging and time consuming. PMID- 1893538 TI - Disinfecting activities of non-peroxide soft contact lens cold disinfection solutions. AB - The antimicrobial activities of three non-peroxide soft contact lens chemical disinfection systems--ReNu Multi-Purpose Solution (0.00005% polyaminopropyl biguanide), Opti-Soft Disinfecting Solution (0.001% polyquaternium-1), and Opti Free Rinsing, Disinfecting & Storage Solution (0.001% polyquaternium-1)--were compared to Soft Mate Disinfecting Solution (0.005% chlorhexidine digluconate). Each product was separately inoculated with each of five microorganisms at approximately 10(6) microorganisms per mL. All of the solutions demonstrated excellent disinfecting activity against Pseudomonas aeruginosa and Staphylococcus epidermidis, with complete disinfection occurring within 4 hours. Only Soft Mate disinfected Serratia marcescens within 4 hours. ReNu reduced the microorganisms to 10-100 cells/mL and Opti-Soft and Opti-Free reduced the number to 10(2)-10(3) cells/mL. For the fungal species, Soft Mate showed excellent activity against Candida albicans (disinfection in 4 hours) and reduced Aspergillus fumigatus to 10(3) spores/mL in 4 hours. After 4 hours ReNu, Opti-Soft, and Opti-Free had reduced C. albicans only slightly, to 10(5) cells/mL and displayed virtually no disinfecting activity against A. fumigatus. For these newer chemical disinfection systems, diligent cleaning and rinsing of the soft contact lenses are the most important steps in the patient care regimen. PMID- 1893537 TI - Clinical evaluation of the Tangent Streak trifocal contact lens. AB - The Tangent Streak trifocal is a rigid gas permeable contact lens with horizontal segments for distance, intermediate, and near correction. We undertook a prospective clinical evaluation of the Tangent Streak trifocal to determine the efficacy of this lens in correcting presbyopic symptoms. Distance, intermediate, and near corrections were compared using visual acuity and contrast sensitivity charts in 25 presbyopic ametropes. Compared to the original bifocal correction, the Tangent Streak trifocal provided 21 of 25 of study patients (84%) with subjectively improved intermediate vision, while maintaining distance and near vision. Twelve of 16 dissatisified bifocal contact lens wearers (75%) were successfully fit with the Tangent Streak trifocal. This study shows that the Tangent Streak trifocal lens can effectively provide multifocal vision to presbyopic ametropes. PMID- 1893539 TI - Clinical application of the oxygen transmissibility of powered contact lenses. AB - Stipulation of the oxygen transmissibility (Dk/L) of a contact lens based upon oxygen permeability (Dk) and nominal lens thickness (L) can be misleading since center thickness, average thickness, and hence Dk/L of a contact lens vary with lens power. While earlier confusion regarding determination of Dk has now been resolved, this data has yet to be fully incorporated into a clinically applicable model. We developed a graphical solution describing variations in Dk/L with power for a representative sample of currently available hydrogel and rigid contact lenses. The Dk/L is found to be optimal for lenses of low minus power (approximately -2.50 D). The model presented here will assist practitioners in assessing the potential oxygen performance of different lens designs with respect to a given power. We advocate that lens manufacturers print the average Dk/L on lens packaging, according to the model described in this paper, along with the parameters that are usually stated. PMID- 1893540 TI - Corneal ulcers associated with contact lenses including experience with disposable lenses. AB - We conducted a retrospective study of corneal ulcers that had been managed on the Cornea Service at Wills Eye Hospital in 1988 and 1989. Forty-four percent (51 of 116) of the ulcers were associated with contact lens use. Pseudomonas was the most often isolated organism (25 of 116, 22%) and was most frequently associated with cosmetic soft contact lenses (16 of 25, 64%). Ulcers associated with disposable contact lenses (five cases) were similar to those associated with conventional extended wear myopic lenses (15 cases). Pseudomonas was the predominant organism with both disposable (four of five, 80%) and conventional extended wear lenses (nine of 15, 60%). Staphylococcus aureus (19 cases) and Staphylococcus epidermidis (19 cases) were the next most frequently isolated organisms and usually occurred in ulcers not associated with contact lenses (29 of 38, 76%). Ulcers were treated 3.3 times more often in people using extended wear than in those using daily wear myopic lenses. Disposable contact lenses have not eliminated the problem of corneal ulcers associated with extended wear contact lenses. PMID- 1893541 TI - Studies on initiation of silicone elastomer lens adhesion in vitro: binding before the indentation ring. AB - We studied silicone elastomer lens binding in vitro to determine what factors may influence its development on the cornea or corneosclera. Lens binding to corneas was not influenced by corneal toricity (0-20 D), corneal fitting relationship (2 D steep to 4 D flat), mucin (2 or 5%) in the tear-bath, or transcorneal pressure (11-22 mm/Hg). In isolated corneas or in whole eyes, transient intraocular pressure changes did not influence keratometry readings, ruling these out as potential mechanisms for corneal binding during sleep. Corneoscleral preparations were also examined to simulate a decentered lens. Corneoscleral binding occurred with a significantly (P less than 0.001) greater frequency than corneal binding and was not influenced by corneal toricity, corneal fitting relationship (up to .5 mm steeper than K), or mucin concentration. Unlike the final stages of clinical lens adhesion, the binding we observed permitted lateral lens movement and occurred without leaving an indentation ring. These findings may suggest that the system models the initiation of corneoscleral binding, involving decentration and suction onto the corneoscleral junction. Corneal binding, however, cannot be explained by a chemical attraction between the silicone elastomer lens surface and cornea, with or without mucin interaction, and must be accounted for by other factors found in vivo. PMID- 1893542 TI - Bandage lenses: collagen shield vs. hydrogel lens. AB - We compared the behavior of a 70% water content hydrogel lens to a 24-hour collagen shield in 11 healthy volunteers. Corneal swelling was measured by means of ultrasound pachymetry. After 24 hours of continuous wear, mean corneal thickness increased 26.4 microns (4%) with the hydrogel lens and 17.9 microns (3%) with the collagen shield, a difference that was not significant at the P less than 0.05 level. Both the hydrogel lens and the corneal shield were well tolerated. Ocular discomfort was slightly greater with the collagen shield. We assume that this is related to the reduction in visual acuity and subsequent loss of binocular vision with the collagen shield. The development of a fully transparent collagen shield would enhance patient compliance and facilitate assessment of the corneal and intraocular status in eye disease. PMID- 1893543 TI - A comparison of the EH-270 corneal topographer with conventional keratometry. AB - The Marco Model-1 keratometer was compared for accuracy and precision with the El Hage Corneal Topography System (EH-270). Five consecutive readings of three steel calibration balls (40.50 D, 42.50 D, 44.75 D), one PMMA hemisphere (48.00 D), and 14 eyes (seven patients) were obtained using each instrument. Keratometry was found to be statistically more accurate and precise for measuring the two steeper steel balls and the hemisphere. Values obtained from patients demonstrated excellent correlation between keratometry and the EH-270. Although more variability was observed in measuring corneas greater than 43.00 D using the EH 270, we found these differences to be clinically acceptable. The EH-270 has a number of clinical advantages. PMID- 1893544 TI - The spectrum of topography found in keratoconus. AB - In order to more completely understand the topographic changes associated with keratoconus we performed computer-analyzed, digitized, videokeratoscopy (CADVK) on 23 patients with clinically documented keratoconus, using the EH-270 Corneal Topographer (Visioptic, Houston, TX). The majority of analyzed eyes demonstrated the classic picture of a well defined zone of inferior to inferotemporal steepening. However, several other topographic patterns were noted, including: nasal, superior, and central steepening, as well as extension of the inferior steepening superiorly. Additionally, significant flattening was found in some portions of the cornea away from the cone, particularly in the superonasal quadrant. In all cases, the precise location and degree of steepening could be easily defined. Interestingly, for both typical and atypical topographic patterns, marked symmetry between eyes in each patient was noted. The use of CADVK may allow for a more thorough appreciation of the diverse and complex topographic abnormalities associated with keratoconus, information which could aid in contact lens management and design. PMID- 1893545 TI - Fungal contact lens infiltration simulating crystalline deposits. PMID- 1893546 TI - Staged therapy for the dry eye. AB - A variety of therapeutic options are now available for treating the dry eye. As a result, an ophthalmologist faced with an untreated dry eye patient will have to select an initial treatment modality from a range of possibilities. More often, however, a dry eye patient will have already been treated with a variety of eye drops, devices, and procedures, so that a fresh approach is needed, following analysis of the patient's current condition. This article reviews one specialist's therapy for dry eye and the rationale for that therapy. An approach is recommended in which treatment of the dry eye is advanced in stages according to the severity of the condition and its response to each level of therapy. PMID- 1893547 TI - Hydrogel keratophakia: long-term morphology in the monkey model. AB - After 8.5 years a rhesus monkey with bilateral hydrogel (Permalens) intracorneal implants was evaluated by light microscopy and transmission electron microscopy to determine the long-term effects of a synthetic plastic upon the primate cornea. Light microscopy revealed that the hydrogel lenticules were implanted between 80 and 90% of stromal depth, causing posterior bulging of the stroma into the anterior chamber; this was also seen clinically with slit-lamp biomicroscopy. Some minor pathologic changes were also found elsewhere in the cornea, including epithelial remodelling anterior to the hydrogel implant and a few vacuolated endothelial cells posterior to the edges of the implant. Histologically, no inflammatory reaction was seen in either cornea. This primate demonstrates the long-term biocompatibility of hydrogel intracorneal lenses. PMID- 1893548 TI - Reducing stroke risk in atrial fibrillation patients. PMID- 1893549 TI - Managing congenital heart defects in adults. PMID- 1893550 TI - Who should treat headache? PMID- 1893551 TI - Carney's complex remains a puzzle. PMID- 1893552 TI - Catheter ablation: a 'charge' into the future. PMID- 1893553 TI - Transcatheter electrical AV junction ablation: predictors of success. AB - The initial and long-term results of transcatheter electrical ablation in 29 patients with drug-refractory supraventricular tachyarrhythmias were analyzed. Ablation was immediately successful (defined as induction of chronic complete heart block) in 25 patients (86.2%). Among the group in whom ablation was unsuccessful, there were more patients with ectopic atrial tachycardia and a higher incidence of narrow QRS escape rhythm following the initial ablation. A His amplitude equal to or greater than 0.3 mV was correlated with success. Complications of ablation included deep venous thrombosis and ventricular arrhythmias. Post-ablation stress testing was superior to ambulatory monitoring in identifying early return of atrioventricular conduction. PMID- 1893554 TI - Factitious anisocoria and orthostatic hypotension. AB - A 30-year-old woman employed by a veterinarian had many episodes of syncope. At presentation, she had anisocoria and premature ventricular beats. Hemodynamic workup revealed only moderate peripheral venous pooling. The circumstances of the fainting spells and eye examination led to the identification of medications which, if taken surreptitiously, will induce the perplexing clinical picture which the patient presented. PMID- 1893555 TI - Prolonged survival with isolated levocardia and situs inversus. AB - Isolated levocardia with situs inversus, or ILSI, is a rare anomaly with a reported incidence of 1:22,000 in the general population and from 0.4% to 1.2% of all patients with congenital heart diseases. It is commonly associated with both congenital heart disease and splenic abnormalities, either asplenia or polysplenia. The prognosis is poor, and only about 5% to 13% of patients survive more than 5 years. The case described here, which had computed tomographic findings, is the first case reported with multiple malignancies associated with ILSI. This patient, at 73 years of age, is the second longest survivor reported in the literature. PMID- 1893556 TI - Evaluation and management of Carney's complex: an illustrative case. AB - Carney's complex is characterized by cardiac and cutaneous myxomas, mammary myxoid fibroadenomas, spotty mucocutaneous pigmentation, primary pigmented adrenocortical disease, large-cell calcifying Sertoli cell tumors of the testis, growth hormone-secreting pituitary adenomas, and psammomatous melanotic schwannomas. We present an illustrative case of Carney's complex in a 26-year-old woman who at age 20 underwent bilateral adrenalectomy for Cushing's syndrome. Six years later, she suffered multiple central nervous system embolic episodes secondary to three cardiac myxomas, which led to her death. Appropriate evaluation and management of patients with Carney's complex is outlined. PMID- 1893557 TI - Strategies for migraine management. AB - According to widely accepted theory, migraine is a self-limited neurogenic sterile inflammation characterized by initial cerebral vasoconstriction, subsequent extracranial and intracranial vasodilation, sterile inflammation, and secondary muscle contraction. It is characterized by recurrent attacks of headache, usually unilateral and accompanied by nausea, vomiting, and, often, other symptoms. Frequency, duration, and intensity of attacks are widely variable. Migraine affects more women than men, and is often related to menses. Patients with classic migraine experience visual or neurologic prodromes, but vague "premonitions" occur in both classic and common migraine. Precipitating factors include foods, alcohol, medications, visual stimuli, changes in routine, and stress. The first-line agent for abortive therapy is ergotamine; corticosteroids are indicated for prolonged headache. Propranolol is recommended for daily prophylactic therapy, and alternatives include calcium channel blockers, nonsteroidal anti-inflammatory agents, and tricyclic antidepressants. PMID- 1893558 TI - Eosinophilia-myalgia syndrome. AB - The eosinophilia-myalgia syndrome is a newly described disease associated with ingestion of a contaminant or byproduct of the amino acid L-tryptophan. Patients typically present with intense myalgias, especially of the extremities, and commonly suffer from skin and subcutaneous manifestations (edema and induration of the skin, morphea-like lesions, pruritus). Less frequent findings are cardiorespiratory involvement (cough, dyspnea, pulmonary infiltrates) and neurologic disease (ascending polyneuropathy). Laboratory findings include blood eosinophilia (greater than 10(9) cells per liter), normal to slightly elevated serum aldolase levels, and negative studies for connective tissue diseases (normal erythrocyte sedimentation rate, negative antinuclear antibodies). Tissue damage in eosinophilia-myalgia syndrome is likely related to infiltration by eosinophils with subsequent release of toxic molecules such as major basic protein. Management in severely ill patients includes administration of corticosteroids. PMID- 1893559 TI - Bilateral renal masses in a 61-year-old man. PMID- 1893560 TI - Tailoring antihypertensive therapy in 1991. AB - Tailored care will increasingly become the hallmark of treatment for patients with hypertension in the 1990s. In mildly hypertensive patients, treatment should begin with nonpharmacologic approaches to lower blood pressure and reduce the patient's cardiovascular risk profile. The ever-increasing array of antihypertensive drugs and drug classes will enable clinicians to select agents based on the advantages and disadvantages for a particular patient, while continuing to move away from the rigid guidelines of stepped care. Physicians more often will base their choice of antihypertensive therapy not on safety and efficacy alone, but rather on the safety and efficacy of the drug in the long term care and the impact of therapy on quality of life. PMID- 1893561 TI - Differentiation and survival of rat olfactory epithelial neurons in dissociated cell culture. AB - Olfactory epithelial neurons in mammals are unique in that they continue to differentiate from precursor cells in the adult. These neurons extend long axons into the olfactory bulb. Previous attempts to grow these cells in dissociated cell cultures at low density, have not been entirely satisfactory. We report that when plated at very low density, rat olfactory epithelial neurons will differentiate morphologically and biochemically when cultured on astrocytes, but not on non-cellular substrata, such as polylysine, laminin or fibronectin. We demonstrate with antibodies, that these olfactory epithelial neurons require N CAM, N-cadherin and L1 for neurite extension. Furthermore, synthetic cadherin peptides containing the tripeptide HAV which is found in the first extracellular domain of N-cadherin, as well as the amino acids flanking this region, appear to be important in cadherin-mediated neurite growth on astrocytes. Astrocytes also appear to enhance the survival and differentiation of olfactory epithelial neurons from embryonic day 15 and 4-5 week post-natal rats, but this effect is not sustained beyond 5 days in cultures of postnatal epithelium. PMID- 1893562 TI - Expression of choline acetyltransferase activity in a co-culture of spinal cord and skeletal muscle cells is inhibited by myogenic differentiation inhibitors. AB - The effect of myogenic differentiation on the expression of choline acetyltransferase (ChAT) activity in co-cultured spinal cord neurons was studied. ChAT activity in spinal cord cells dissociated from 14-day mouse embryos was markedly increased when co-cultured with skeletal myotubes from 20-day embryos. This enhancement of ChAT activity was not observed in the presence of concanavalin A (ConA) or N-methyl-1-deoxynojirimycin (MDJN) which inhibits myoblast fusion, creatine phosphokinase and acetylcholinesterase activities in muscle cells. ChAT activity in spinal cord neurons cultured alone was unaffected by these agents. The inhibitory effect of ConA and MDJN was reversible, with an almost full recovery of ChAT activity following removal of the agents. Addition of ConA or MDJN after myotube formation exerted little inhibitory effect on ChAT activity. The effects of ConA and MDJN on ChAT activity in co-cultures were comparable to those on creatine phosphokinase and acetylcholinesterase. These observations indicate that the neurotrophic effects of skeletal muscle cells on spinal cord neurons are dependent on the differentiation state of the muscle cells. PMID- 1893563 TI - Developmental gradients of vasoactive intestinal polypeptide (VIP)-containing neurons in the rat visual cortex detected by image analysis. AB - The postnatal development of vasoactive intestinal polypeptide-immunoreactive (VIP-IR) neurons was followed by computer-assisted image analysis in the rat visual cortex. The laminar distribution of all VIP-IR structures was measured. These structures were subdivided into cell somata, dendritic profiles and axonal boutons and measured separately. VIP-IR neurons were first seen on postnatal day 1, mostly in the upper half of the presumptive visual cortex. A localization of cell bodies similar to that in the adult is reached between days 12 and 16. VIP IR dendrites have a protracted growth period as compared to perikarya, involving a developmental gradient from an even distribution to a concentration in the upper cortical layers. This is due to the formation of dendritic terminal arbors after the second postnatal week. Scattered VIP-IT axonal boutons appear on day 3 in the midportion of the presumptive visual cortex. Their typical laminar distribution in layers II, IV and lower VI was observed after day 12. Our results suggest that the biochemically detected sharp increase in VIP levels after the second postnatal week is due to the maturation of cell processes as a morphological basis of neuronal connectivity. PMID- 1893564 TI - Epidermal growth factor and its receptor in the developing human nervous system. AB - Recent data suggest that epidermal growth factor and epidermal growth factor receptors (EGF/EGF-R) are present and functional in neurons within the central nervous system. Previously, EGF was detected in developing and mature rat brain and cerebrospinal fluid. Also, EGF-R was documented in discrete locations in normal adult human brain, as well as in senile plaques associated with Alzheimer's disease. Using two polyclonal sera, anti-EGF and anti-EGF-R, in conjunction with immunohistochemical staining, we examined formalin-fixed, paraffin-embedded neural tissues from 10 autopsied, human brains. These specimens were collected from patients who died during various stages of development ranging from 27 weeks of estimated gestational age to 63 years of age. Immunostaining for EGF and EGF-R was detected in hippocampal pyramidal cells. Purkinje cells, large multipolar neurons of the dentate nucleus, anterior horn cells, dorsal root ganglion cells, cells of the dorsal nucleus of Clark, intermediolateral column cells and ependymal cells. Positive binding studies with 125I-EGF confirmed that numerous EGF receptors are unoccupied, assessable, and available for interactions with potential ligands such as EGF and TGF alpha in developing rat brains. It appears that EGF and/or EGF-R may play a role during maturation and differentiation of the human central nervous system. PMID- 1893565 TI - Human fetal central nervous system organotypic cultures. AB - Many aspects of human neurodevelopment remain enigmatic. A main reason for this is, although there have been a significant number of morphologic and biochemical studies of neural tissues derived from human embryos and fetuses, this can only provide a static picture of the events at a given gestational age. Also, in vitro studies that focus on cells derived from these tissues have a limitation in that different cell types in dissociated tissue culture cannot interact in a 'normal' physiologic manner thereby, perhaps, altering their housekeeping and luxury functions. The present study focused on the development of a human explant organotypic culture model that may overcome the static limitation of the first example and permit a dynamic analysis of different cell types as they interact which may satisfy the second restriction. Because there is an array of developmental markers that define different cell phenotypes, this explant model may also provide a means of analyzing, for the first time, processes undefined in the human CNS. Human fetal CNS tissue obtained from second trimester abortuses was established in culture. The tissues were maintained for up to 12 weeks during which time they developed and differentiated. Sample cultures were harvested periodically and analyzed by light- and electron microscopy in combination with immunocytochemistry. Differentiation of neurons, astrocytes, oligodendrocytes and endothelial cells was documented using morphologic and biochemical criteria. As such, this model system may allow for the analysis of processes that occur during normal human fetal neurodevelopment and in pathologic conditions. PMID- 1893567 TI - Effects of changes in the periphery on development of the corticospinal motor system in the rat. AB - Effects of changes in the periphery on development of the corticospinal (CS) motor system were studied in the rat. Unilateral forelimb restraint between ages 5 and 30 days resulted in an increase in the number of CS neurons which persisted in the adult. The effect was most marked ipsilateral to limb restraint where both crossed and uncrossed CS connections were increased, but it also occurred to a lesser extent on the contralateral side. Animals with limb restraint had enlargement of the areas of cerebral cortex in which CS neurons occurred. The enlargement of motor cortex regions and increase in CS neurons closely resembled the changes found in the remaining cerebral hemisphere after neonatal hemispherectomy. The findings in animals with forelimb restraint differed markedly from those after forelimb amputation, where little change occurred in either number or location of CS neurons. Limb restraint initiated at the time of postnatal hemispherectomy had no effects on location or number of CS neurons beyond those of hemispherectomy alone. It is proposed that transient CS axons that occur normally in the postnatal rat may be recruited for formation of permanent connections under very diverse conditions, i.e. hemispherectomy and limb restraint. Failure to observe an additional effect of limb restraint in hemispherectomized animals may be due to the fact that after hemispherectomy all available transient fibers in the remaining hemisphere are recruited for innervation of the side of the spinal cord that has lost its cortical input. PMID- 1893566 TI - Distribution of phosphoprotein p19 in rat brain during ontogeny: stage-specific expression in neurons and glia. AB - p19 is an evolutionarily highly conserved 19-kDa cytosolic protein that undergoes hormonally regulated phosphorylation in a variety of mammalian cells. Its expression is abundant in brain and testis and is developmentally regulated. Here we have used immunocytochemistry to define the cell types expressing p19 in the rat CNS during pre- and postnatal development. p19-like immunoreactivity appears in young postmitotic neurons in the mantle zone of the neural tube on embryonic day 12-13. Subsequently, it is abundant in most, if not all, early immature forms of both neurons and glia and declines to undetectable levels in fully differentiated cells. In adult brain, strong p19-like immunoreactivity remains detectable in selective regions, primarily where production of glia and neurons is known to persist, such as the subventricular zone of olfactory bulb and lateral ventricle, and the dentate gyrus. The abundance of p19 mRNA, determined by Northern blot analysis of selected brain regions, parallels the distribution of p19 assessed by immunocytochemistry, suggesting that control of p19 expression is pretranslational. Together with previous findings on the transient expression of p19 during spermatogenesis, the present data suggest that expression of p19 occurs in a number of cell lineages in a differentiation stage-dependent manner. In brain, p19 represents a new marker that may prove valuable for defining immature cell populations. PMID- 1893568 TI - Fibroblast growth factor-induced increased survival of cholinergic mesopontine neurons in culture. AB - Basic fibroblast growth factor (bFGF) was found to increase the survival of immunocytochemically-identified cholinergic mesopontine neurons in dissociated cell cultures of embryonic rat midbrain. In contrast, cultures exposed to, (a) bFGF and an antibody to bFGF, (b) antibody to bFGF alone, or (c) untreated, contained approximately half the number of cholinergic neurons compared to bFGF treated cultures. PMID- 1893569 TI - Differential development of cortical taste areas in granular and dysgranular insular cortices in rats. AB - Recordings were made from taste neurons in granular and dysgranular areas of the insular cortex of anesthetized SD-rats from the age of 4 days to over 90 days (adults). Almost all of the taste neurons were detected in the dysgranular area prior to weaning, but the number in the granular area increased with age and exceeded the number in the dysgranular area after the age of 50 days. In the dysgranular area, most taste neurons, irrespective of the postnatal age, were located at layer 5. However, in the granular area they were found at a deeper layer, with the advance in age; e.g. layer 2-3 at 14-20 days to layer 5 in adults. Thus, taste afferents in granular and dysgranular areas of the insular cortex differ with advance in age. PMID- 1893570 TI - Rapid enhancement of transplant-mediated pupilloconstriction after elimination of competing host optic input. AB - Retinae transplanted over the brainstem, when directly illuminated, cause pupilloconstriction in the host eye. This occurs even when the host eye is maintained in darkness. If the host optic nerve is then severed, the transplant mediated response is substantially augmented within 1-2 days. It is suggested that this is due to enhancement of the signal-to-noise ratio resulting from elimination of dark discharge in the host optic nerve. PMID- 1893571 TI - Chemiluminescent and bioluminescent techniques. AB - Light-emitting chemical reactions (chemiluminescence, CL) and biological reactions (bioluminescence, BL) have a diverse range of analytical applications but relatively few have been adopted by routine clinical laboratories. Advantages of CL and BL assays include sensitivity (attomole and sub-attomole detection limits), speed (signal generated in a few seconds and in some cases stable for several hours), nonhazardous reagents, and simple procedures. The most promising clinical applications are in immunoassay, protein blotting, and DNA probe assays. Chemiluminescent molecules exploited as labels include luminol, isoluminol, acridinium esters, thioesters and sulfonamides, and phenanthridinium esters. Separation and nonseparation assays have been devised, based on isoluminol and acridinium ester labels. The combination of the amplification properties of an enzyme and a CL or BL detection reaction provides a highly sensitive analytical system. Since 1983, CL and BL methods have been developed for many enzyme labels, e.g., alkaline phosphatase, glucose-6-phosphate dehydrogenase, horseradish peroxidase, Renilla luciferase, and xanthine oxidase. Currently, the most successful enzyme assays are the enhanced CL method for a peroxidase label involving a mixture of luminol, hydrogen peroxide, and an enhancer (e.g., p iodophenol) and the direct CL method for alkaline phosphatase, with an adamantyl 1,2-dioxetane phenyl phosphate as substrate. Both systems are very sensitive (the detection limit for alkaline phosphatase when using the dioxetane reagent is 0.001 amol) and produce long-lived light emission (greater than 30 min), which is ideal for membrane applications in which light emission is detected with photographic film or a charge-coupled device camera. PMID- 1893572 TI - Polymerase chain reaction and Q beta replicase amplification. AB - The polymerase chain reaction (PCR) and Q beta replicase are two methods in which nucleic acid polymerases are used for amplification. Although these approaches share many similar problems concerning target contamination and probe specificity, they differ dramatically in their mechanisms of action and modes of application. The PCR method amplifies target sequences between two priming oligonucleotides and in essence amplifies a portion of the analyte. Q beta replicase, on the other hand, amplifies a specific template molecule hybridized to target sequences and therefore amplifies a signal component of the system. For this reason, Q beta replicase amplification has applications in areas other than for the detection of nucleic acid sequences. The requirements for application and the advantages of both PCR and Q beta replicase amplification are reviewed. PMID- 1893573 TI - High-sensitivity laser-induced fluorescence detection for capillary electrophoresis. AB - Capillary electrophoresis provides very high efficiency separations of biological molecules. Laser-induced fluorescence produces very high sensitivity detection. The combination of the two techniques results in an analytical tool with unprecedented properties: separations with more than a million theoretical plates and detection limits of a few hundred analyte molecules. This paper considers the design of high-sensitivity laser-induced fluorescence detection for capillary zone electrophoresis separation of labeled amino acids and capillary gel electrophoresis separation of DNA sequencing fragments. PMID- 1893574 TI - Atomic force microscopy: seeing molecules of lipid and immunoglobulin. AB - The atomic force microscope (AFM) can image individual molecules by raster scanning a sharp tip over a surface. In this paper we present molecular resolution images of immunoglobulin M (IgM) and of ultraviolet light-polymerized films of the lipid dimethyl-bis(pentacosadiynoyloxyethyl) ammonium bromide ("BRONCO"). The polar head groups of individual lipid molecules can be resolved on the surface of this and other lipid films. These lipid films also provide a good substrate for AFM imaging of DNA and of other molecules such as antibodies. Because the AFM scans surfaces, it is most often successful at imaging either molecules that can form an array on a surface or molecules that are quite firmly attached to a surface. The ability of the AFM to operate under water, buffers, and other liquids makes it possible to study biological molecules under conditions in which they are physiologically active. Imaging of the actual molecular process of fibrin polymerization shows the potential of the AFM for studying biological processes. In the six years since its invention, the AFM has excited much interest and has imaged molecules in a wide range of systems. PMID- 1893575 TI - Optical biosensor assay (OBA). AB - We describe a new biosensor immunoassay involving optical diffraction to detect clinically important analytes in human body fluids. A silicon wafer is used as a support for immobilization of antigen or antibody. The protein-coated surface is illuminated through a photo mask to create distinct periodic areas of active and inactive protein. When the surface is incubated with a positive sample, antigen antibody binding occurs only on the active areas. Upon illumination with a light source such as a laser, the resulting biological diffraction grating diffracts the light. A negative sample does not result in diffraction because no antigen antibody binding occurs to create the diffraction grating. The presence or absence of a diffraction signal differentiates between positive and negative samples, and the intensity of the signal provides a quantitative measure of the analyte concentration. The technique is demonstrated with a quantitative assay of choriogonadotropin in serum. PMID- 1893576 TI - Time-resolved fluorescence detection of enzyme-amplified lanthanide luminescence for nucleic acid hybridization assays. AB - A new nonisotopic detection method based on time-resolved fluorescence for nucleic acid hybridization assays with alkaline phosphatase labels has been developed: enzyme-amplified lanthanide luminescence (EALL). EALL combines the amplification of an enzyme label with the sensitivity and background elimination of time-resolved fluorescence detection of lanthanide ion luminescence. The detection system for alkaline phosphatase makes use of a phosphorylated salicylic acid derivative that, upon dephosphorylation, gives a product capable of forming a luminescent terbium chelate. We demonstrate DNA hybridization assays by using two substrates, one for membrane and one for solution-based formats. Using the substrate that produces a more adhesive product allows performance of dot-blot and Southern blot assays on nylon membranes; results can be recorded with a time resolved photographic camera system, or with an ultraviolet transilluminator based system. Less than 4 pg of target sequence can be detected in a dot-blot assay after incubation with substrate for 2-4 h. DNA microwell-plate hybridization assays with the more soluble substrate/product pair can be quantified with time-resolved fluorescence plate readers, giving a similar detection sensitivity. EALL is thus a practical time-resolved fluorescence-based alternative to other detection systems for DNA hybridization assays. PMID- 1893577 TI - Sensitive, colorimetric enzyme amplification cascade for determination of alkaline phosphatase and application of the method to an immunoassay of thyrotropin. AB - A highly sensitive flavin adenine dinucleotide-3'-phosphate (FADP)-based enzyme amplification cascade has been developed for determining alkaline phosphatase (ALP; EC 3.1.3.1). The cascade detects ALP via the dephosphorylation of the novel substrate FADP to produce the cofactor FAD, which binds stoichiometrically to inactive apo D-amino acid oxidase (D-AAO). The resulting active holo D-AAO oxidizes D-proline to produce hydrogen peroxide, which is quantified by the horseradish peroxidase-mediated conversion of 3,5-dichloro-2 hydroxybenzenesulfonic acid and 4-aminoantipyrine to a colored product. The FADP based enzyme amplification cascade has been used in a novel releasable linker immunoassay (RELIA) to quantify thyrotropin (TSH). In the assay, TSH is first captured onto antibody-coated chromium dioxide particles. After formation of an antibody-TSH sandwich with a dethiobiotinylated second antibody, the complex is reacted with a streptavidin-ALP conjugate. Biotin is then used to release the conjugate into solution, and ALP is quantified in an automated version of the FADP-based amplification cascade on the aca discrete clinical analyzer (Du Pont). The sensitivity of the colorimetric RELIA assay for TSH (less than 0.1 milli-int. unit/L) is comparable with that of fluorometric assays. This technology provides a way to adapt to the aca high-sensitivity immunoassays for a wide range of analytes via colorimetric detection. PMID- 1893578 TI - Encapsulation of europium in liposomes for use in an amplified immunoassay detection system. PMID- 1893580 TI - The IMMULITE assay tube: a new approach to heterogeneous ligand assay. PMID- 1893579 TI - Interference-free method for glycated proteins in serum and whole blood, based on a boronate reagent. PMID- 1893581 TI - Sensitive fluorescence method for detecting DNA-ligation amplification products. PMID- 1893582 TI - Use of polymerase chain reaction for detecting DNA contaminants in pharmaceutical recombinant products. PMID- 1893583 TI - Immunoassay for determining low- and high-Mr antigens with a dry multilayer film. PMID- 1893585 TI - Enhanced chemiluminescence in filter-based DNA detection. PMID- 1893584 TI - Advances in ultrasensitive detection of proteins and nucleic acids with chemiluminescence: novel derivatized 1,2-dioxetane enzyme substrates. PMID- 1893586 TI - Implementation of NCCLS and alternative method-evaluation protocols. PMID- 1893587 TI - Retrospective time-resolved testing: model I--time-resolved glycohemoglobin. PMID- 1893588 TI - Abbott prism: a multichannel heterogeneous chemiluminescence immunoassay analyzer. AB - We describe a multichannel heterogeneous immunoassay analyzer in which a sample is split between disposable reaction trays in a group of linear tracks. The system's pipettor uses noninvasive sensing of the sample volume and disposable pipet tips. Each assay track has (a) a conveyor belt for moving reaction trays to predetermined functional stations, (b) temperature-controlled tunnels, (c) noncontact transfer of the reaction mixture between incubation and detection wells, and (d) single-photon counting to detect a chemiluminescence (CL) signal from the captured immunochemical product. A novel disposable reaction tray, with separate reaction and detection wells and self-contained fluid removal, is used in conjunction with the transfer device on the track to produce a carryover-free system. The linear immunoassay track has nine predetermined positions for performing individual assay steps. Assay step sequence and timing is selected by changing the location of the assay modules between these predetermined positions. The assay methodology, a combination of microparticle capture and direct detection of a CL signal on a porous matrix, offers excellent sensitivity, specificity, and ease of automation. Immunoassay configurations have been tested for hepatitis B surface antigen and for antibodies to hepatitis B core antigen, hepatitis C virus, human immunodeficiency virus I and II, and human T-cell leukemia virus I and II. PMID- 1893589 TI - The integrated blood-collection system as a vehicle into complete clinical laboratory automation. AB - A rationale is offered and methodology illustrated for integrating the fundamental steps involved in the collection and processing of blood for laboratory evaluation. The approach taken in the development of these concepts and components greatly extends the possibilities of laboratory systems integration without upsetting established modalities. A prototype design of the integrated blood-collection system integrates blood collection, cellular separations, sample transfer to stable storage without chemical mediators, and sample presentation for chemical analysis (e.g., precision metering) while preserving patient identification. A sophisticated, multi-chambered blood collection container is the site of all blood sample processing and transfer steps. This device is supported by a compact, robotic centrifuge of unique design and a transfer mechanism to facilitate sample delivery for analysis within a diagnostic instrument. The confluence of these individual components into a single integrated system provides the means to completely automate the processing of blood samples, after sample collection, eliminating all manual transfer steps and any external exposure of blood interfaces outside the diagnostic instrument. Configurational derivatives of the Integrated Blood-Collection System offer choice of skin or venipuncture procedure, rapid plasma extraction for micro- or macro-collected volumes, and sample delivery by either aspiration or direct metering of discrete 10-microL samples from the collection container. The skin puncture configuration provides the opportunity within a single device to collect and process up to 500 microL of sample by capillarity from a skin prick. PMID- 1893590 TI - Dear Dr. [Bence] Jones... PMID- 1893591 TI - Novel solid-phase assay of ketone bodies in urine. AB - This simple dip-and-read color-matching assay measures ketone bodies in urine. The result is matched with any of the seven colors provided in a color chart. The intensity and hue of the color formed depends on the concentration of acetoacetic acid and follows a gradation starting from light purple (0.2 mol/L acetoacetate) to dark purple and finally to dark violet (9 mol/L). The color developed is independent of pH in the range pH 4-9.5, and is stable for at least 1 h. 3 Hydroxybutyric acid produced no color at the concentrations tested (less than or equal to 100 mmol/L), and acetone was detectable only when greater than or equal to 15 mmol/L. The test was compared with the Ames Ketostix assay in subjects who were on restricted-calorie weight-loss programs. The two methods showed good agreement, except that 20% (21/103) of samples that were negative by Ketostix were read as positive by the new method, which may be more sensitive (detection limit = 0.2 mmol/L). Measurement of urine ketones was unreliable (in comparison with measurement of blood or breath acetone) for monitoring the rate of fat loss during a negative calorie balance. PMID- 1893592 TI - Total arsenic in urine: palladium-persulfate vs nickel as a matrix modifier for graphite furnace atomic absorption spectrophotometry. AB - We evaluated the effectiveness of nickel and palladium with or without added potassium persulfate as matrix modifiers for the determination of total arsenic in urine. Complete recovery of pure aqueous solutions of As(III), As(V), cacodylic acid (DMA), monomethylarsinic acid (MMA), and o-arsanilic acid was attained by using both nickel and palladium modifiers. Combined arsenobetaine and arsenocholine (so-called fish arsenic), extracted from a certified control material of dogfish muscle (DORM-1), were completely recovered with Pd-S2O8 matrix modification, but not with nickel. Excellent agreement with target values for arsenic in urines from the Centre de Toxicologie du Quebec, supplied by the Interlaboratory Comparison Program, was attained irrespective of the arsenic source when we used Pd-S2O8 as the matrix modifier. PMID- 1893593 TI - Statistical criteria for separate reference intervals: race and gender groups in creatine kinase. AB - Previously published data confirming differences in creatine kinase (EC 2.7.3.2) among various race and gender subgroups in the Los Angeles area have been re examined with use of recently proposed statistical criteria for defining separate reference intervals. Results indicate that one criterion may be too lenient, whereas another is clearly too restrictive in suggesting the need for separate intervals. Further experience with other analytes in both large and small population samples would be helpful. PMID- 1893594 TI - Elimination of matrix and spectral interferences in the measurement of lead and cadmium in urine and blood by electrothermal atomic absorption spectrometry with deuterium background correction. AB - Direct measurement of lead and cadmium in blood and urine by electrothermal atomic absorption spectrometry with deuterium background correction (D2-AAS) is prone to severe matrix and spectral interferences. We overcame these effects by coating the L'vov platform with ammonium molybdate, reducing the atomization time, introducing a post-atomization cooling step, carefully selecting ashing and atomization temperatures, and using an appropriate procedure for matrix modification. To determine Pb and Cd in blood and urine, we used matrix-matched calibration curves. With the proposed procedure for sample preparation, both Pb and Cd in whole blood can be determined in the same diluted sample. Results obtained by D2-AAS correlate closely with those by Zeeman-corrected AAS. Detection limits (mean blank + 3 SDblank) for Pb in urine and blood were 4 micrograms/L. For cadmium, the detection limits were 0.4 and 0.1 micrograms/L for urine and blood analysis, respectively. Between-run CVs were less than 5.0%. PMID- 1893595 TI - Inclusion of proteins into calcium oxalate crystals precipitated from human urine: a highly selective phenomenon. AB - The abundance of protein in the matrix of calcium oxalate uroliths has fueled speculation regarding its role in stone genesis. In this study, we wanted to characterize the composition of the proteins associated with early stages of calcium oxalate crystallization in urine. Calcium oxalate crystallization was induced in urine from healthy men and women by the addition of an oxalate load. The crystals were harvested and demineralized, and the proteins remaining were separated and characterized by polyacrylamide gel electrophoresis and Western blotting. Most urinary proteins were not detected in the crystals or were present in only small quantities. The most abundant urinary macromolecule, Tamm-Horsfall glycoprotein, was notably absent from the crystal extracts. The predominant protein associated with the crystals, a previously unknown urinary constituent that we call crystal matrix protein (CMP; molecular mass, 30,000 Da), was more prevalent in the crystals derived from female urine. We conclude that most urinary proteins play no direct role in calcium oxalate crystal formation. However, the protein CMP exhibits a remarkable affinity for calcium oxalate crystals and may be important in stone pathogenesis. PMID- 1893596 TI - Enzymatic digestion, solid-phase extraction, and gas chromatography/mass spectrometry of derivatized intact oxazepam in urine. AB - Enzymatic digestion with beta-glucuronidase (EC 3.2.1.31) was used to release intact oxazepam from urine samples containing the d5-analog internal standard. The resulting specimens were extracted with Du Pont PREP Type W cartridge (processed by a PREP Automated Sample Processor), Bond Elut Certify, and J.T. Baker "spe" columns for comparison of the columns' extraction recovery and overall effectiveness. Methyl iodide/tetrahexylammonium hydrogen sulfate and N,O bis(trimethylsilyl)trifluoroacetamide/trimethylchlorosilane (10 g/L) were used for the methylation and trimethylsilylation studies. We used a Hewlett-Packard HP 5790 mass-selective detector equipped with a 13-m J & W DB-5 column (5% phenyl polysiloxane phase) for gas chromatography/mass spectroscopy (GC/MS) analysis and the Thru-Put Target software package for data processing. After several exploratory experiments, we adopted the Du Pont PREP system methylation procedure because of its effective recovery, the superior stability of the derivatization product, the possibility of incorporating a clean-up step, and the potential for high throughput. The extraction recovery from a set of control samples was 87%. Coefficients of variation obtained for six replicates of GC/MS analysis and for the overall procedure were 1% and 3%, respectively. Excellent linearity was established in the 50-8000 micrograms/L concentration range studied. With the use of 3-mL samples, a 20-microL final reconstitution volume, oxazepam at 50 micrograms/L was easily detected under the adopted operation conditions. PMID- 1893597 TI - Detection of genetic variants of alpha 1-antitrypsin with site-specific monoclonal antibodies. AB - The serum protein alpha 1-antitrypsin (alpha 1-AT) serves as the major inhibitor of neutrophil elastase. The most common allele of the alpha 1-AT gene is designated as PiM. The Z mutation is a single-base substitution of the normal M allele, causing a Glu----Lys change at position 342 in the molecule. The ZZ phenotype is associated with a severe deficiency of alpha 1-AT, serum concentrations of the protein being 10% of normal. Individuals with an alpha 1-AT deficiency are at an increased risk of developing emphysema. To generate antibodies that specifically detect the 342 position in the context of the flanking sequences, we synthesized several peptides that included the 342 position for both the M and the Z variant. Immunization with variant-specific peptide-carrier conjugates elicited alpha 1-AT variant-specific responses, as determined in a direct enzyme-linked immunoassay. Monoclonal antibodies (MAbs) were selected with different specificity for the 342 region: MAbs F43 recognize only the alpha 1-AT sequence with 342Glu, i.e., all variant proteins that are non Z, either from hetero- or homozygous individuals; MAbs F50 recognize only the sequence with 342Lys, i.e., all Z-variant proteins in ZZ or heterozygous individuals; MAbs F46 recognize alpha 1-AT with either 342Lys or 342Glu, all variant proteins with sequences as in the peptides used. Z homo- and heterozygotes were detected with our MAbs in a rapid and simple immunoblot assay. Other variants (M, S, and F) can also be assigned on the basis of the electrophoretic pattern. This sensitive detection method is very easy, rapid, and straightforward and provides a powerful tool for diagnosis of the alpha 1-AT deficiencies, allowing early treatment (augmentation of alpha 1-AT) and proper advice on lifestyle practices. PMID- 1893598 TI - Reaction tray and noncontact transfer method for heterogeneous chemiluminescence immunoassays. AB - We describe a reaction tray for a heterogeneous chemiluminescence (CL) immunoassay having the following features: separate sample incubation and signal detection wells; a design that allows for noncontact transfer of the reaction mixture from incubation wells to detection wells; surface features to mate with a detector and create a light-tight seal for CL detection; and self-contained means for liquid removal. The reaction mixture is transferred by injecting a wash solution from a group of nozzles into the incubation well. Quantitative transfer of microparticles (transfer efficiencies greater than 95% and CV less than 5%) is achieved by injecting two 300-microL pulses of transfer solution at a rate of 2.1 m/s. The performance of the tray and method of transfer is tested by determining the precision of CL signal for a sample containing a concentration of anti hepatitis B core antigen (anti-HBc) or hepatitis B surface antigen (HBsAg) close to the cutoff value for the assay. PMID- 1893599 TI - Development of an enzyme-linked immunosorbent assay of apolipoprotein E-AII complex in plasma. AB - Measurement of apolipoprotein (apo) E-AII complex in human plasma is important in determining the role of apoE in lipoprotein metabolism. In this paper, we demonstrate a new and simple method to determine apoE-All complex by using an enzyme-linked immunosorbent assay. Anti-apoE IgG (goat) was used as a capture antibody, and captured apoE-All complexes were detected by an anti-apoAll (rabbit) horseradish peroxidase-conjugated anti-rabbit IgG (goat) system. With this method, apoE-All complex was specifically determined without the interference of apoAll and was not affected by apoE monomer less than 250 mg/L. The content of the complex in reference serum, a normolipidemic serum pooled from five subjects with phenotype E3/E3, was arbitrarily defined as 100%. The coefficients of variation were 3.5%-6.3% within assay and 8.8%-11.6% between assays. PMID- 1893600 TI - Lack of effect of acute alcohol ingestion on plasma lipids. PMID- 1893601 TI - Effect of diagnostic radioisotope administration on routine radioimmunoassay results. PMID- 1893602 TI - Measurement of urinary tobacco markers in a smoking-cessation program. PMID- 1893603 TI - Unusual hyperthyroxinemia caused by endogenous thyroxin antibodies. PMID- 1893604 TI - Urinalysis with an Abbott EPx Spectrum analyzer. PMID- 1893605 TI - Abbott TDx "selective" assay overestimates cyclosporine in whole blood. PMID- 1893606 TI - Effect of storage time on peptic activity in gastric biopsies. PMID- 1893607 TI - Urinalysis in the 10th century. PMID- 1893608 TI - Influence of transplantation of parathyroid glands on blood pressure development in stroke prone spontaneously hypertensive rats and in normotensive Wistar Kyoto rats. AB - The influence of the parathyroid glands (PTG) on the development of high blood pressure (BP) in stroke prone spontaneously hypertensive (SHR/SP) and Wistar Kyoto (WKY) rats has been studied. After ablation of their own PTG's SHR/SP received PTG's from WKY rats and vice versa. After transplantation (TRPL) a normal calcium and parathyroid hormone (PTH) status was preserved during the whole observation period. One group of animals received a high salt diet (8% NaCl) for 4 weeks after transplantation, the other group received a normal rat chow for 3 months. In SHR/SP, which had PTG-transplants from WKY rats, the development of BP was clearly attenuated compared to sham operated rats in both experimental groups. WKY rats with PTG's from SHR/SP became hypertensive after two weeks during salt loading and after six weeks under normal diet. Sham operated WKY rats remained normotensive. The results demonstrate that the parathyroid gland is involved in the pathogenesis of hypertension, but the only known secretory product of PTG's parathyroid hormone, seems not to be responsible for these effects. PMID- 1893609 TI - Proteinase activity in isolated glomeruli of Goldblatt hypertensive rats. AB - In Goldblatt rats, the kidney exposed to high blood pressure reveals glomerulosclerosis. Moreover, in preexisting parenchymal renal disease, the development of glomerulosclerosis is accelerated in the unclipped kidney. Up to now, the pathogenetic mechanism underlying the development of glomerulosclerosis due to systemic hypertension has not completely been resolved. Traditionally, hemodynamic mechanisms have been discussed. This study was performed to investigate whether there might be a decreased activity of glomerular proteinases in the unclipped kidney of Goldblatt rats as a potential pathogenetic factor for glomerulosclerosis. 20 weeks after the surgical intervention, we found a reduced proteinase activity in ultrasonically destroyed isolated glomeruli obtained by differential sieving technique in comparison with the contralateral clipped kidney and the kidneys of sham-operated normotensive controls. This could be confirmed, when proteinase activity was related to DNA instead of protein. When investigating glomerular cathepsin B-content, a lysosomal enzyme, which is able to degrade glomerular structural as well as non-structural proteins, we found a decreased level in the kidney of Goldblatt rats exposed to systemic hypertension in comparison with normotensive control animals. Basing on these results we presume that glomerular protein accumulation and concomitant glomerulosclerosis due to systemic hypertension might be a result of a synergistical interaction between hemodynamic factors and biochemical ones; we suggest one of the latter to be a decreased glomerular proteinase activity. PMID- 1893611 TI - Effect of circulating factors on vascular smooth muscle contraction and its calcium uptake in uremia. AB - Uremia is often associated with alterations in calcium metabolism and vascular smooth muscle function in hypertension and atherosclerosis. The ways in which these conditions inter-relate are not clearly understood. In order to study the possibility that circulating factors might influence smooth muscle function, experiments were performed on rat aortic strips. The serum from both uremic patients and rats enhanced the norepinephrine-induced contraction (NEIC) and net 45-calcium uptake in rat aortic strips. In a similar manner, the serum of parathyroidectomized uremic rats also increased the NEIC, whereas verapamil reduced the aortic response to levels below those of the control, in the presence of uremic serum. These findings suggest that in both chronic (patients) and early (rats) stages of uremia, there is a circulating factor, different from parathyroid hormone, that affects calcium uptake and vascular smooth muscle contraction. PMID- 1893610 TI - Elevated 18-hydroxy-corticosterone in inbred salt-sensitive rats. AB - Rats susceptible to the hypertensive effect of dietary salt (SS/Jr) have excess 18-hydroxydeoxycorticosterone (18-OH-DOC) and 19-nor-DOC compared to control rats (SR/Jr). This may be caused by an abnormal adrenal 11 beta-hydroxylase, which catalyzes the 11 beta, 18, and 19-hydroxylations of DOC. A comparison of the urinary products of this enzyme including 18-OH-DOC, 19-nor-DOC, corticosterone (B), and 18-OH-B have not been described in the SS/Jr. Therefore, these steroid products were measured at 7 and 12 weeks of age in 36 weanling male and female, SS/Jr and SR/Jr (n = 9 in each group), on a low-salt diet. In both the male and female SS/Jr urinary free levels of 18-OH-DOC, 19-nor-DOC, and 18-OH-B were elevated, while B was not different at 6 and 10 weeks of age. The largest increases were in 18-OH-B levels, and these levels correlated with 18-OH-DOC and B but not 19-nor-DOC. The high degree of correlation between these steroids probably reflects their closely related dependence on adrenal 11 beta-hydroxylase biosynthesis. PMID- 1893612 TI - Increased dietary sodium chloride in patients treated with antihypertensive drugs. AB - Eleven patients on a normal diet with mild to moderate essential hypertension satisfactorily treated with diverse hypotensive agents entered a randomized double-blind cross-over study to evaluate the effect of additional sodium chloride (100 mmol slow sodium) compared with placebo on blood pressure control over a 6 week period. Despite excellent tablet compliance, sodium chloride failed to significantly alter mean supine or erect blood pressure. These findings as well as a review of the relevant literature suggest that excess dietary sodium does not jeopardize blood pressure control in such patients. PMID- 1893613 TI - Additive combination studies of captopril and ditekiren, a renin inhibitor, in nonhuman primates. AB - Additive combination studies of an angiotensin converting enzyme (ACE) inhibitor, captopril, and a renin inhibitor, ditekiren (U-71038), were carried out in conscious sodium-depleted and sodium replete cynomolgus monkeys. The agents elicited dose-additive hypotensive responses regardless of the order of drug administration in sodium-depleted monkeys. A dose-additive blood pressure response was also observed when the administration of captopril was preceded by ditekiren in conscious sodium replete monkeys. None of the animals in these groups exhibited significant alterations of heart rate. An apparent over-additive hypotensive response, accompanied by tachycardia, occurred in sodium replete monkeys when ditekiren was administered after captopril. It was proposed that the captopril-induced hyperreninemia may have allowed the blood pressure to become partially renin-dependent and therefore susceptible to the inhibitory action of ditekiren. The results of these studies suggested that both ditekiren and captopril elicited cardiovascular effects in conscious cynomolgus monkeys via a decreased formation of angiotensin II. PMID- 1893614 TI - Tissue distribution of mucosal antibody-producing cells specific for respiratory syncytial virus in severe combined immune deficiency (SCID) mice engrafted with human tonsils. AB - Groups of C.B-17 SCID mice were reconstituted intraperitoneally with human tonsillar mononuclear cells (hu-TMC) from children seropositive for antibody to respiratory syncytial virus (RSV) and subsequently challenged intraperitoneally with inactivated RSV or sham-immunized. The synthesis and the distribution characteristics of human antibody to RSV in various murine tissues were studied using an enzyme-linked immunospot assay (ELISPOT). No specific antibody was observed in sham-immunized animals. In contrast, mice engrafted with hu-TMC exhibited the appearance of specific human antibody secreting cells (hu-ASC) after i.p. immunization with inactivated RSV. RSV-specific hu-ASC were detected only in animals engrafted with cells from donors seropositive for antibodies to Epstein-Barr virus. Hu-TMC engrafted mice showed RSV-specific IgM and, in lower numbers, IgG hu-ASC in several tissues including the lungs. Numbers of RSV specific IgA hu-ASC were low, however, and detected only in the lung. No RSV specific hu-ASC were detected in the intestine. These data demonstrate for the first time that hu-TMC-SCID chimeras respond to immunization with viral antigen. Furthermore, the results suggest that hu-TMC engraft in lungs but not in the intestinal tissue. PMID- 1893615 TI - A study of immune responses to myelin and cardiolipin in patients with systemic lupus erythematosus (SLE). AB - Sera from 39 patients with SLE, 20 patients with cerebrovascular disease with no evidence of SLE, and 20 normal controls were tested for antibodies to cardiolipin (CL), brain total upper (UPG) and lower phase (LPG) glycolipids, myelin basic protein (MBP), myelin, and single strand DNA (ssDNA) by ELISA. Binding to the glycolipids and MBP was negative or negligible in all the groups, but significant binding was observed against CL, myelin and ssDNA in some of the SLE patients. Many sera from SLE patients with cerebral disorders and high CL binding also demonstrated high binding to myelin. These sera also labelled cell surface antigens on neonatal mouse neurons and astrocytes by immunofluorescence in tissue culture. A correlation was found to exist between anti-CL and antimyelin antibodies in SLE patients with cerebral lesions, but not between anti-ssDNA and anti-CL antibodies. As much as 80-90% of the specific activity of these antibodies could be absorbed out by the relevant antigens but only partially by the other antigens. In the control groups binding was low and no specific absorption could be demonstrated. PMID- 1893616 TI - Immune adherence and clearance of hepatitis B surface Ag/Ab complexes is abnormal in patients with systemic lupus erythematosus (SLE). AB - Complement levels and complement receptor 1 (CR1) on erythrocytes (E) are reduced in systemic lupus erythematosus (SLE). To see whether these abnormalities are responsible for defective transport and elimination of immune complexes (IC) from the circulation, patients with active SLE (14) and normal volunteers (14) were injected with preformed IC (hepatitis B surface Ag/Ab). Two minutes after injection only 25.9 +/- 19.1% (mean +/- 1 s.d.) of the circulating IC were bound to E in the SLE patients as compared to 63 +/- 3.7% in the normal subjects (P = 0.0001). For SLE patients, the reduced immune adherence was best explained by a combination of complement depletion and low CR1 binding capacity (tau = 0.80, P = 0.0001). The disappearance of IC as estimated from the area under the elimination curve was faster in SLE than in controls (P = 0.02), and correlated with CR1 (tau = 0.54, P = 0.0001) and immune adherence observed in vivo (tau = 0.33, P = 0.013). Finally, immune adherence was absent and IC disappeared very rapidly in a patient with C2 deficiency and an SLE-like disease. These observations suggest that in SLE the defective immune adherence reaction might be responsible for the accelerated disappearance of IC from the circulation. PMID- 1893617 TI - IgG human monoclonal anti-DNA autoantibodies from patients with systemic lupus erythematosus. AB - We describe the production of six mouse-human heterohybridomas secreting human IgG anti-dsDNA antibodies derived from patients with systemic lupus erythematosus (SLE). Peripheral blood cells used for fusion experiments were from patients who were shown to have high numbers of anti-DNA secreting B cells in the peripheral blood. All monoclonal antibodies bind to dsDNA in ELISA systems, five are reactive with Crithidia lucilae kinetoplasts and three precipitate dsDNA in the Farr assay. Inhibition studies revealed a remarkable specificity for certain polynucleotide structures. To our knowledge these are the first hybridomas described in the human system that secrete anti-dsDNA antibodies of the IgG class. PMID- 1893618 TI - Impaired tumour necrosis factor-alpha (TNF-alpha) production and abnormal B cell response to TNF-alpha in patients with systemic lupus erythematosus (SLE). AB - We examined the TNF-alpha activity in culture supernatants of monocytes isolated from the peripheral blood of patients with SLE and of normal individuals. The monocytes from patients with SLE stimulated with silica particles, lipopolysaccharide or Staphylococcus aureus Cowan 1 secreted significantly lower amounts of TNF-alpha than did normal monocytes. A decreased TNF mRNA expression was observed in peripheral blood mononuclear cells stimulated by mitogens from patients with SLE. Furthermore, we examined the effect of recombinant TNF-alpha (rTNF-alpha) on the B cell function in SLE patients. rTNF-alpha inhibited the spontaneous B cell proliferation of SLE, but tended to enhance the normal B cell proliferation. Spontaneous IgM production from SLE B cells was inhibited by rTNF alpha, but that from normal B cells was not. Spontaneous IgG production was unaffected by rTNF-alpha. Also, rTNF-alpha did not affect the viability of B cells. These findings suggest that an impaired TNF-alpha production and an abnormal B cell response to TNF-alpha play a role in the immunological dysfunction in patients with SLE. PMID- 1893619 TI - Tumour necrosis factor/cachectin plays a key role in autoimmune pulmonary inflammation in lupus-prone mice. AB - The role of tumour necrosis factor-alpha (TNF-alpha) in the development of autoimmune pulmonary inflammation has been investigated in lupus-prone mice. An increase in TNF-alpha mRNA level from whole lung preparation of lupus-prone mice was evident, from 3 weeks to 12 weeks during growing process, as shown by Northern blot analysis, but not in control mice. Furthermore, it is also found that the major source of this increase in TNF-alpha mRNA was attributed to infiltrating mononuclear cells found within the lung. Treatment of lupus-prone mice with rabbit anti-mouse TNF-alpha IgG prevented the development of pulmonary inflammation lesions such as lung fibrosis and alveolitis. These results suggest that an increased TNF-alpha production by infiltrating mononuclear cells in the lungs of lupus-prone mice may play a role in the development of autoimmune pulmonary inflammation and in significant changes of cytokines and the immune responses in pulmonary inflammation lesions of lupus-prone mice. PMID- 1893620 TI - The effect of anti-neutrophil cytoplasm autoantibodies on the signal transduction in human neutrophils. AB - The effect of anti-neutrophil cytoplasm autoantibodies (ANCA) on neutrophil activation was studied by pre-incubating neutrophils with IgG and F(ab')2 prepared from ANCA patients with Wegener's granulomatosis or microscopic polyarteritis. We measured the generation of inositol triphosphate (IP3) (a product of hydrolysis of membrane phospholipid which acts as a second intracellular messenger), and the translocation of protein kinase C (PKC) upon stimulation by a chemotactic peptide, fMet-Leu-Phe (fMLP). ANCA+ F(ab')2 did not induce a significant increase in IP3 generation. Nonetheless, ANCA+ F(ab')2 and ANCA+ IgG pretreatment of human neutrophils reduced the production of inositol phosphates upon subsequent fMLP stimulation compared with experiments performed when cells were pretreated with F(ab')2 and IgG prepared from ANCA- healthy subjects. A significantly reduced generation of IP3 and inositol biphosphate (IP2) was observed. ANCA+ F(ab')2 pretreatment of neutrophils inhibited fMLP stimulated IP3 generation in a dose-dependent manner. The membrane-bound PKC activity upon stimulation by FMLP and PMA was reduced in neutrophils pretreated with ANCA+ F(ab')2 and IgG. These results indicate that ANCA affect in vitro signal transduction (IP3 generation, and translocation of PKC) in human neutrophils. Apparently, further activation of signal transduction by chemotactic peptide is significantly blunted in cells pre-incubated with ANCA+ F(ab')2 but not with F(ab')2 from healthy controls. PMID- 1893621 TI - Anti-IL-1 alpha autoantibodies in patients with rheumatic diseases and in healthy subjects. AB - We have developed a quantitative assay for IgG autoantibodies against IL-1 alpha using protein A-Sepharose CL-4B. We examined the autoantibodies in sera from 107 healthy subjects, 151 patients with rheumatoid arthritis (RA), 64 patients with systemic lupus erythematosus (SLE) and 16 patients with systemic sclerosis. The frequency of positive sera for the autoantibodies in patients with RA was 16.6%, which was about three times more frequent (P less than 0.01) than that in healthy subjects (5.6%) or that in patients with SLE (4.7%). Only one serum of 16 patients with systemic sclerosis was positive for the autoantibodies. Neutralizing activity of the autoantibodies was demonstrated by murine thymocyte proliferation assay. The concentrations of IgG at 50% inhibition of IL-1 alpha (15 pM) induced thymocyte proliferation ranged between 0.1 and 0.5 mg/ml. A time course study showed fluctuations of the titres of the autoantibodies in parallel with the disease activity of RA. These results suggest that the anti-IL-1 alpha autoantibodies present in the sera and possibly some other body fluids may be involved in the regulation of IL-1 activity in vivo. PMID- 1893622 TI - Humoral autoimmune response to ribosomal P proteins in chronic Chagas heart disease. AB - The C terminal region of a Trypanosoma cruzi ribosomal P protein, encoded by the lambda gt11 JL5 recombinant, defined a major antigenic determinant in chronic Chagas heart disease. Immunopurified anti-JL5 antibodies were tested for anti human ribosome reactivity by immunoblotting. They recognized the parasite ribosomal P proteins and clearly reacted with the corresponding human P proteins. The peptide R-13, that comprises the 13 C terminal residues of the JL5 recombinant and defines the specificity shared between chronic Chagas heart disease anti-JL5 antibodies and the systemic lupus erythematosus (SLE) anti-P antibodies, was used to study the specificity and the IgG subclass distribution of the anti-R-13 response by ELISA. The R-13 autoepitope is recognized mainly by sera from chagasic patients, but not by sera from malaria patients. Moreover, there was a significant correlation between anti-R-13 antibody levels and anti-T. cruzi antibody titres. The anti-R-13 response was mainly restricted to the IgG1 heavy chain isotype and correlated with the anti-T. cruzi isotype distribution. PMID- 1893623 TI - A 72-kD B cell-associated surface glycoprotein expressed at high levels in hairy cell leukaemia and plasma cell neoplasms. AB - The present paper describes two new MoAbs, GHI/75 and VMP55, which were raised against a glycoprotein enriched lysate of hairy cell leukaemia. These antibodies recognized a new antigen of 72 kD (unreduced) and 83 kD (reduced) molecular weight. GHI/75 and VMP55 gave very strong staining of plasma cells, moderate labelling of circulating B cells but only weak staining of monocytes, some tissue macrophages and lymphoid cells. Neither antibody reacted with neutrophils or any non-haematopoietic cells. Both antibodies, however, strongly labelled the tumour cells in hairy cell leukaemia, multiple myeloma, plasmacytoma and lymphoplasmacytic lymphomas. No staining was seen of the neoplastic cells in Hodgkin's disease, myeloid leukaemia or T cell lymphomas. The two antibodies, GHI/75 and VMP55, may be of value in the differential diagnosis of hairy cell leukaemias and plasma cell neoplasms. In addition, the ease with which their antigen can be purified provides the possibility for a detailed study of this molecule. PMID- 1893625 TI - Reduced frequency of nickel allergy upon oral nickel contact at an early age. AB - From animal studies we know that oral administration of T-dependent antigens before sensitization effectively induces systemic immune unresponsiveness. Such 'oral tolerance' is persistent, dose-dependent, antigen-specific and presumably T suppressor cell-mediated. Oral tolerance induction could be an effective way to prevent undesired T cell-mediated immune functions, such as playing a role in allograft reaction, autoimmune and allergic diseases. In the present study allergic contact hypersensitivity (ACH) to nickel, currently presenting the most frequent contact allergy in man, was chosen to establish the feasibility of oral prevention of undesired T cell-mediated immunity in man. Potentially tolerizing (oral nickel contacts via orthodontic braces) as well as sensitizing (ear piercing) events were studied retrospectively in 2176 patients attending nine European patch test clinics. Patients were interviewed by means of a confidential questionnaire. The results show that ear piercing strongly favoured development of nickel ACH. More importantly, patients having had oral contacts with nickel releasing appliances (dental braces) at an early age, but only if prior to ear piercing, showed a reduced frequency of nickel hypersensitivity. Frequencies of other hypersensitivities, in particular to fragrance, were not affected. These results support our view that induction of specific systemic immunologic tolerance by timely oral administration of antigens is feasible in man. PMID- 1893624 TI - Increased luminol-enhanced chemiluminescence of blood monocytes and granulocytes in Hodgkin's disease. AB - The oxidative metabolic burst of blood monocytes and polymorphonuclear leukocytes (PMN) from 22 untreated patients with Hodgkin's disease (HD) and 18 healthy subjects were studied. Monocytes and PMN were enriched by density centrifugation and in vitro activated by zymosan. The oxidative metabolism was measured by luminol-enhanced chemiluminescence (CL). The CL of the patients' monocytes and PMN was higher than that of controls (P less than 0.01 and P less than 0.05, respectively). Patients with stage II-IV HD showed an increased blood monocyte CL as compared with stage I patients (P less than 0.05). Furthermore, patients with lymphocytic depletion or mixed cellularity subtype demonstrated an increased CL of PMN as compared with the remainder. Enhanced CL of phagocytes has been observed in chronic inflammatory disease and can be induced by various serum factors such as monokines and immune complexes. The present study demonstrates an increased CL of blood-borne phagocytic cells in untreated HD. Furthermore, CL of blood monocytes and PMN correlated to tumour burden and histologic subtype, respectively. PMID- 1893627 TI - Pigeon breeders' lung: pigeon intestinal mucin, an antigen distinct from pigeon IgA. AB - Antigens identified by indirect immunofluorescence staining and specific for sera from patients with pigeon breeders' lung or healthy pigeon breeders, have been isolated from pigeon intestinal mucus. Two antigenic peaks, one pigeon intestinal mucin and the other IgA, were separated by equilibrium centrifugation of water soluble mucus in a caesium chloride density gradient. Antigenic positive material was identified by a modified double-sandwich ELISA, by inhibition of haemagglutination of turkey erythrocytes and by gel diffusion. Antigenic-positive material co-fractionated on gel-filtration with purified intact and papain digested pigeon mucin, both free of IgA. These studies demonstrate antibodies to two quite different antigens are associated specifically with sera from pigeon breeders, a novel antigen pigeon intestinal mucin and the previously documented pigeon IgA. PMID- 1893626 TI - Antibody-dependent cell-mediated cytotoxicity to beta-lactoglobulin-coated cells with sera from children with intolerance of cow's milk protein. AB - The capacity of serum antibodies against beta-lactoglobulin to mediate antibody dependent cell-mediated cytotoxicity (ADCC) was analysed in sera from children with cow's milk protein intolerance (CMPI). The children with CMPI were divided into three groups according to clinical features: delayed-onset CMPI with gastrointestinal symptoms (n = 8); immediate-onset CMPI with gastrointestinal and skin symptoms (n = 8); and immediate-onset CMPI with skin symptoms only (n = 8). The CMPI groups were compared with children with untreated (n = 9) or treated (n = 8) coeliac disease and a control group (n = 22). Sera from the children were examined for cytotoxic effects using lymphocytes from healthy adults as effector cells and radiolabelled beta-lactoglobulin-coated erythrocytes from the same donor as target cells. In addition, IgG and IgA serum antibodies against beta lactoglobulin were determined with ELISA. Sera from children with CMPI and gastrointestinal symptomatology showed a significantly increased capacity to induce ADCC reactivity as compared with controls. This increased capacity was seen in sera from those with immediate as well as delayed onset of the gastrointestinal symptoms. In contrast, sera from children who had an immediate onset CMPI with only skin symptoms mediated no such increase in ADCC reactivity. Moreover, children with coeliac disease with a few exceptions, demonstrated low ADCC reactivity, despite the fact that they had high levels of antibodies against beta-lactoglobulin. ADCC may be an immunopathogenic mechanism in certain cases of CMPI with gastrointestinal symptoms. PMID- 1893628 TI - Anti-thyroid peroxidase antibodies in sera from healthy subjects and from patients with chronic thyroiditis: differences in the ability to inhibit thyroid peroxidase activities. AB - A significant percentage (6.4%) of healthy subjects was found to contain anti thyroid peroxidase (TPO) antibodies in their sera. However, in contrast with IgG from sera of patients with chronic thyroiditis, IgG from sera of healthy subjects did not inhibit TPO activities both in guaiacol and iodide assays. In addition, anti-TPO antibodies from healthy subjects did not block the inhibition of enzyme activities by anti-TPO antibodies from patients. These findings suggest that anti TPO antibodies from healthy subjects do not bind to the epitopes relating to substrate-combining sites of TPO. Thus, the specificities of anti-TPO antibodies in healthy subjects may differ from those in cases of chronic thyroiditis. PMID- 1893629 TI - Circulatory antigen of Heymann nephritis. III. Presence of the 70-kD circulatory protein in the immune deposits of Heymann nephritis. AB - An antigen of 70 kD size has been isolated previously from normal rat serum which has immunological cross-reactivity to the Heymann nephritis antigen, F x 1A. Its role in the pathogenesis of Heymann's nephritis was unknown. In this investigation we tested for the presence of 70-kD circulatory antigen in the glomerular immune deposits of Heymann's nephritis. Further, its presence was correlated with severity of disease. It was observed that the presence of the 70 kD antigen strongly correlated with the existence of electron-dense deposits in the lamina rara externa (LRE) of the glomerular capillary wall and with pathologic proteinuria. Temporally, the presence of the 70-kD antigen in the immune deposits was followed by large electron-dense deposits, enhanced complement activity and proteinuria. The data suggest that in the growing immune complex lattice in the LRE, the 70-kD circulatory antigen by virtue of its small size, mobility and antigen cross-reactivity facilitates cross linking and coalescence of immune complexes, resulting in electron-dense immune deposits (EDD) formation which initiates complement activation and consequent proteinuria. PMID- 1893630 TI - Proliferative and cytotoxic responses to mannoproteins of Candida albicans by peripheral blood lymphocytes of HIV-infected subjects. AB - Mucosal candidiasis is one of the first opportunistic diseases in HIV-infected subjects. In order to understand the relationship between this disease and immunodeficiency to chemically defined, immunodominant Candida antigens, a mannoprotein fraction from C. albicans cell wall (GMP) was used to analyse proliferative and non-MHC-restricted cytotoxic responses of peripheral blood mononuclear cells (PBMC) from normal and HIV-infected subjects. In the former, GMP induced extensive blastogenesis, generation of powerful cytotoxicity against a tumour cell line (K562), and production of substantial amounts of interferon gamma (IFN-gamma). Cultured PBMC from HIV-infected subjects manifested an early decreased ability for proliferative as well as differentiative cytotoxic responses to the candidal mannoproteins. This inability became clearly evident in subjects with stage III (CDC) of the disease, was total in CDC stage IV and occurred even in some subjects with a normal number of CD4+ cells. Low or absent response to GMP correlated with lack of response to tetanus toxoid. In contrast, both lymphoproliferative and cytotoxic responses to exogenous IL-2 was highly preserved at all stages of infection. The production of IFN-gamma in GMP stimulated PBMC cultures critically fell to negligible values in most of the subjects in CDC stages II and III. Thus, the lowered or absent cell-mediated immune responses to candidal mannoprotein may be one factor to explain the early, elevated susceptibility of HIV-infected subjects to mucosal candidiasis. This study also shows that our mannoprotein preparation may be used as a probe to detect the overall efficiency of T cell responses in the above subjects. PMID- 1893632 TI - Changes in phenotypically distinct mucosal macrophage populations may be a prerequisite for the development of inflammatory bowel disease. AB - Previous studies have demonstrated the presence of much more marked macrophage heterogeneity in colonic mucosa affected by the idiopathic inflammatory bowel diseases (ulcerative colitis and Crohn's disease) than in normal mucosa. This study examines the morphology, distribution and phenotypic expression of mucosal macrophage-like cells in biopsies from patients with idiopathic inflammatory bowel disease in comparison with disease control samples from patients with colonic infection or ischaemia. Approximately 80% of macrophage-like cells in histologically normal mucosa co-express the antigens recognized by the monoclonal antibodies RFD1 (an interdigitating cell marker) and RFD7 (a marker for mature tissue macrophages). In idiopathic inflammatory bowel disease, the normal colonic macrophage population is partly replaced by cells staining positively with RFD7 alone, and, to a lesser extent, with RFD1+ dendritic cells. Sections from patients with infections and ischaemia exhibited epithelial HLA-DR positivity and infiltration of the lamina propria by a more heterogeneous population of macrophages than that seen in histologically normal mucosa. However, the displacement of the normal colonic macrophage phenotype by RFD7+ tissue macrophages occurred to a significantly greater extent in idiopathic inflammatory bowel disease than in disease control mucosa. A pathognomonic feature of the ulcerative colitis and Crohn's colitis sections was the clustering of RFD9+ epithelioid cells at the bases of disrupted crypts and adjacent to areas of mucosal damage. It is concluded that a degree of macrophage heterogeneity and macrophage infiltration can occur as a non-specific response to colonic mucosal damage. The distinctive feature of idiopathic inflammatory bowel disease mucosa is the almost complete replacement of the normal colonic mucosal macrophage population by tissue macrophages and epithelioid cells, and this phenomenon may be important in promoting the development of a chronic inflammatory state. PMID- 1893631 TI - Beta-casomorphin (BCM) and human colonic lamina propria lymphocyte proliferation. AB - BCM is a milk-derived peptide with opiate-like properties which is absorbed through the gastrointestinal mucosa. It has been shown to affect gastrointestinal motility, absorption and secretion. Recently, modulation of the immune system by BCM was also reported. In this study we investigated the in vitro effect of BCM on the human mucosal immune response as represented by lamina propria lymphocyte (LPL) proliferation. Results show that BCM significantly inhibited concanavalin A (ConA) stimulated LPL DNA synthesis. BCM also inhibited ornithine decarboxylase activity (ODC) in ConA-stimulated LPL. Although BCM also inhibited 12-O tetradecanoyl phorbol-13-acetate (TPA) stimulated LPL DNA synthesis, the degree of inhibition was much lower than in ConA-stimulated LPL. The anti-proliferative effect of BCM was reversed by the opiate receptor antagonist, neloxone. Our results suggest that BCM may affect the human mucosal immune system, possibly via the opiate receptor. PMID- 1893633 TI - Analysis of the molecular mimicry between HLA-B27 and a bacterial OmpA protein using synthetic peptides. AB - In spite of a lack of sequence 'homology' between HLA-B27 and the bacterial OmpA outer membrane proteins, they both react with the Ye-2 monoclonal anti-HLA-B27 antibody. The Ye-2 antibody also reacted positively in ELISA with a synthetic peptide derived from the segment spanning residues 63-84 of B*2705. The critical peptide residues were determined by testing first with overlapping peptides, followed by a replacement set made according to the determined epitope. The results were compared with those with overlapping eight mers made to span a carboxyl fragment of the Escherichia coli OmpA protein. They indicate the reason why Ye-2 reacts with both sets of peptides is because it has a preference for polymers of arginine. PMID- 1893634 TI - Immunosuppression follows systemic T lymphocyte activation in the burn patient. AB - A general consensus that thermal injury affects T lymphocyte function adversely is supported particularly by the observation that burned patients' lymphocytes secrete reduced levels of biologically active IL-2 in vitro. In the same patients, however, high serum concentrations of the low-affinity IL-2 receptor (IL2R alpha), a product of an IL-2-activated gene, have been observed. In this study a significant proportion of patients also demonstrated over-physiological levels (from 2 to 500 U/ml) of serum IL-2 ascertained by immunoassay. Increases in serum IL-2 content correlated significantly (P less than 0.02) with those of serum IL-2R alpha during the first week post-burn. Later, serum IL-2R alpha levels continued to increase up to 30 days while IL-2 eventually declined. Thus, augmented secretion of IL-2R alpha appears related to the high serum IL-2 content. Therefore refractoriness to further immune stimulation may be due to early activation of the lymphoid system, rather than to an intrinsic incapacity of T lymphocytes for generating sequential responses. PMID- 1893636 TI - Corticosteroid can alter antigen expression on alveolar macrophages. AB - Normal healthy volunteers underwent broncho-alveolar lavage and the cells obtained were cultured for 24 h and 48 h, either alone or in the presence of the corticosteroid, Budesonide. Cell differentials were all normal, the lavages containing greater than 90% alveolar macrophages. Cytospins of these cells were prepared before and after culture. The cytospins were subjected to immunocytochemical analysis using a panel of MoAbs selected to identify subsets of macrophages and functionally relevant surface antigens. In particular, the expression of RFD1 (antigen presenting cell marker) and RFD7 (mature phagocyte marker) were studied. Before culture, BAL macrophages could be divided into two subsets. Of the cells, 39.3% were RFD1+ and 47.2% were RFD7+. Culture with Budesonide was seen to reduce the proportions of RFD1+ cells to 38% while increasing the RFD7+ population to 69% of total. These changes were relatively specific as Budesonide failed to alter the expression of CD68 or Fc(IgG) receptors. Down-regulation of HLA-DR expression was seen, however, after 24 h contact with Budesonide. As these changes could have functional significance, these data support the hypothesis that steroids may have direct effects on the role of alveolar macrophages in immune responses in the lung. PMID- 1893637 TI - Hypertension and vascular disease in the 1990s. AB - Many pharmacologic agents are effective in normalizing blood pressure in the hypertensive patient. The major issues in antihypertensive therapy today transcend control of blood pressure and focus, instead, on safety considerations, patient acceptance, and additional benefits to target organs. With the drugs currently available, 10-15% of patients withdraw from therapy because of undesirable clinical side effects. Nonclinical side effects such as hyperlipidemia, hypokalemia, and hyperglycemia can limit the clinician's choice of drugs, especially for elderly patients. Antihypertensive agents should also limit target organ damage. The prevalence of stroke can be reduced solely by controlling blood pressure, but inhibition of cardiac ischemic events requires use of specific classes of agents. Beta blockers reduce mortality and reinfarction postmyocardial infarction, whereas angiotensin-converting enzyme (ACE) inhibitors affect several factors leading to heart failure, including cardiac and vascular hypertrophy, remodeling and dilatation postmyocardial infarction, and arrhythmias. Specific actions on intrarenal and other vascular dynamics may make these drugs appropriate for use in patients with diabetes and perhaps hypertensive kidney disease and systemic arterial disease. The range of options available in antihypertensive therapy in the 1990s affords the physician the opportunity to meet additional goals of therapy, specific for each patient. PMID- 1893635 TI - Lymphokine-activated killer (LAK) cells modulate the effects of IL-2 on a T cell mediated immune response. AB - The ability of LAK cells and/or IL-2 to affect the course of an established T cell response was examined in a delayed-type hypersensitivity (DTH) model. IL-2 greatly increased the magnitude of the response at 24 h, while LAK cells alone had no effect. The administration of LAK cells and IL-2 together also had no effect on the magnitude of the DTH response, demonstrating that LAK cells were able to remove the enhancement seen with IL-2 alone. The presence of LAK cells reduced the serum half-life of IL-2 significantly, but not to an extent able to account for the observed loss of IL-2 induced DTH enhancement. IL-2 administration influenced cell phenotypes in the spleen and draining lymph nodes (DLN), as well as increasing splenic weight; the additional presence of LAK cells markedly altered these effects of IL-2 in the spleen (but not the DLN). Taken together, these results suggest that LAK cells interact with activated T-cells within the immune system and modulate their function. PMID- 1893638 TI - Dose-response studies with benazepril in mild to moderate hypertension. AB - The dose-response curve for benazepril, a new angiotensin-converting enzyme inhibitor, has been established from a systematic series of controlled clinical studies in patients with mild to moderate essential hypertension. The studies included a dose-ranging study, four dose-response studies (placebo-controlled or crossover), and four titration trials. The dose-response studies involved 803 patients and evaluated doses from 2 to 80 mg. Analysis of the data revealed the existence of a dose-response relationship over the dosage range of 10 to 80 mg given once daily. Efficacy of once-daily administration was shown by the persistence of significant blood pressure reduction over the 24-h dosing interval. In addition, the net trough-to-peak ratio (an indicator of net antihypertensive effect at the end of the dosing interval) was generally greater than 50%. The dose-determination studies with benazepril were conducted according to a well-designed strategy in which parameters were carefully defined. Based on these trials, the initial dosage for benazepril appears to be 10 mg once daily. Additional response may be observed at dosages up to 80 mg once daily. PMID- 1893639 TI - Comparison of benazepril and other antihypertensive agents alone and in combination with the diuretic hydrochlorothiazide. AB - The safety and efficacy of benazepril, as monotherapy or as part of combination therapy with the diuretic hydrochlorothiazide, have been assessed in a number of studies, including comparative trials with the antihypertensive agents propranolol and nifedipine. These studies have included over 1300 patients with mild-to-moderate hypertension. Comparisons of the efficacy of benazepril and hydrochlorothiazide alone and in combination have shown that benazepril 20 mg once daily is as effective as or more effective in lowering diastolic blood pressure than hydrochlorothiazide 25 mg once daily and that the combination of benazepril 20 mg and hydrochlorothiazide 25 mg has a possibly synergistic effect on diastolic blood pressure. The results of comparative trials of benazepril with propranolol and nifedipine suggest that benazepril, administered alone or with the diuretic hydrochlorothiazide, is as effective as the other antihypertensive agents alone or in combination with hydrochlorothiazide. An additional study demonstrated that the combination of benazepril and nifedipine further lowered diastolic blood pressure in patients not responding to monotherapy with these agents. The safety of monotherapy with benazepril was found to be similar to that of the other antihypertensive agents. Safety of the combination of benazepril and hydrochlorothiazide was shown to be better than that of the combination of propranolol and hydrochlorothiazide. An attenuation of adverse experiences observed during nifedipine monotherapy was obtained when benazepril was added to the nifedipine regimen. PMID- 1893640 TI - Safety profile of benazepril in essential hypertension. AB - Data from clinical trials with benazepril suggest that the safety profile of benazepril is similar to that of other angiotensin-converting enzyme (ACE) inhibitors. Treatment-related side effects occurred in 20% of benazepril-treated patients and in 18% of patients receiving placebo. The most commonly reported side effects with benazepril were headache, dizziness, and fatigue. The incidence of side effects was not affected by the degree of hypertension, age, gender, race, dosage, or the degree of renal impairment. Side effects believed to be related to the pharmacologic action of ACE inhibitors as a class include symptomatic hypotension, which occurred at a relatively low rate with benazepril, and hyperkalemia and elevation of serum creatinine, which occurred to the same extent with benazepril as has been noted with other ACE inhibitors. The mechanism of cough as an ACE inhibitor side effect is unknown; the incidence was similar to that with other ACE inhibitors. Rash and taste disturbance have occurred rarely with benazepril. The incidence of neutropenia and of proteinuria was the same in both the benazepril and placebo groups. Renal failure in hypertensive patients treated with benazepril has not been reported. Overall, benazepril is generally well tolerated by hypertensive patients. The incidence of most side effects is comparable to that with other ACE inhibitors and placebo. PMID- 1893642 TI - The pharmacokinetics of benazepril relative to other ACE inhibitors. AB - Benazepril is a prodrug that, following rapid conversion to benazeprilat, is a potent nonsulfhydryl inhibitor of angiotensin-converting enzyme. The absorption, bioactivation, distribution, and elimination of benazepril and benazeprilat have been evaluated in healthy subjects, hypertensive patients, and patients with characteristics known to alter the pharmacokinetic disposition of ACE inhibitors, such as renal impairment, hepatic impairment, and advanced age. Following oral administration, benazepril is absorbed and transformed into benazeprilat in the liver. Coadministration of benazepril with food delays absorption slightly but does not affect the ultimate bioavailability of benazeprilat. Severe hepatic impairment slows conversion of benazepril to benazeprilat but does not affect the overall bioavailability of benazeprilat; thus dosage adjustment is not necessary in the hepatically impaired population. Mild-to-moderate renal impairment (creatinine clearance greater than 30 ml/min) slightly increases benazeprilat concentrations; severe renal impairment (creatinine clearance less than 30 ml/min) reduces benazeprilat elimination and requires dosage reduction. In elderly patients, benazepril disposition is the same as in younger patients, although benazeprilat clearance is slightly reduced. No clinically significant drug-drug interactions occur with benazepril and many other medications commonly prescribed to elderly hypertensive patients. The pharmacokinetic characteristics of benazepril are stable over a wide range of conditions, and dosage adjustments for pharmacokinetic reasons are required infrequently. PMID- 1893641 TI - ACE inhibitors in renal disease. AB - Recent experimental studies suggest that the resistance state of the preglomerular and postglomerular capillary arterioles may determine if a particular class of antihypertensive agents will protect the kidney from hemodynamically mediated glomerular injury. This review discusses (1) the effects of angiotensin II on the renal microcirculation, (2) the pathophysiology of essential hypertensive renal disease, (3) the renal pharmacology of angiotensin converting enzyme (ACE) inhibitors, and (4) the hypothesis that renal protection is dependent on control of systemic and glomerular hypertension. PMID- 1893643 TI - Hypertensive mechanisms and converting enzyme inhibitors. AB - The introduction of angiotensin-converting enzyme (ACE) inhibitors marks a new era in the understanding and treatment of high blood pressure. Although the benefits of therapy with ACE inhibitors are documented, it is more difficult to isolate the principal mechanisms that account for their effective actions in the treatment of hypertension. Recent data suggest that these agents affect both the pressor and depressor mechanisms that regulate vascular tone and cardiac function. For example, ACE inhibitors decrease angiotensin II-mediated vasoconstriction, reduce adrenal medullary catecholamine release, restore baroreceptor activity, and normalize vasomotor sympathetic activity. Experimental work indicates that ACE inhibitors also act on hypertensive mechanisms via actions on the central nervous system. Cardiovascular centers in the brain have receptor sites for angiotensin II and contain the proteins required for local synthesis of angiotensins. Vasomotor neurons possess such receptors and exhibit ACE activity. In addition, angiotensin II receptors involved in the regulation of baroreceptor activity are present in neuronal elements of the baroreflex arc. It is suggested that ACE inhibitors reach the brain via circumventricular organs to reduce sympathetic activity and enhance baroreceptor sensitivity. New studies suggest that depressor actions of ACE inhibitors include enhanced biosynthesis of vasodilator prostaglandins. From animal experiments it is deduced that enhanced production of angiotensin-(1-7) after inhibition of ACE stimulates release of vasodilator prostaglandins. These investigations clarify the function of tissue renin-angiotensin systems in the control of blood pressure in both normal and hypertensive states. PMID- 1893644 TI - Control of blood pressure by the renin-angiotensin-aldosterone system. AB - Modification of the renin-angiotensin system, part of a powerful feedback system for long-term control of arterial pressure and volume homeostasis, through use of angiotensin-converting enzyme (ACE) inhibitors, offers a powerful means of reducing blood pressure in many hypertensive patients. There is considerable evidence to suggest that the chronic renal and blood pressure actions of ACE inhibitors are mediated mainly by blockade of angiotensin II formation, rather than by other effects such as increased levels of kinins or prostaglandins. The long-term actions of angiotensin II and aldosterone on blood pressure are closely intertwined with their effects on volume homeostasis and the renal pressure natriuresis mechanism. In most instances, changes in angiotensin II and aldosterone act to amplify the effectiveness of pressure natriuresis and minimize changes in blood pressure needed to maintain sodium balance. When angiotensin II or aldosterone levels are inappropriately elevated, the antinatriuretic effects of these hormones shift pressure natriuresis to higher levels, thereby necessitating increased blood pressure to maintain sodium balance. Control of renal excretory function and modulation of pressure natriuresis by angiotensin II is mediated by intrarenal and extrarenal effects, including stimulation of aldosterone secretion. Current evidence indicates that the intrarenal effects of angiotensin II are quantitatively more important than changes in aldosterone in regulating renal excretion and arterial pressure. The intrarenal actions of angiotensin II include a direct effect on tubular sodium transport as well as a potent constrictor action on efferent arterioles, which increases reabsorption by altering peritubular capillary forces. The constrictor effect of angiotensin II on efferent arterioles also helps to stabilize glomerular filtration rate and therefore excretion of metabolic waste products, an action that may be particularly important when renal perfusion is impaired (e.g., in renal artery stenosis or heart failure). PMID- 1893645 TI - Cardioprotective potential of angiotensin-converting enzyme inhibitors. AB - Antihypertensive drugs have various effects, both positive and negative, on metabolic and hemodynamic risk factors for coronary artery disease. Cardioprotective effects of angiotensin-converting enzyme (ACE) inhibitors have recently been described. The benefits of ACE inhibition include not only a reduction in blood pressure but also improved insulin responsiveness, prevention of potassium loss, diminished myocardial oxygen demand, suppression of catecholamines, and interaction with bradykinin and prostaglandins. These benefits result in improved perfusion of vital organs, diminished cardiac work, and protection of coronary vessels, evident in improved left ventricular systolic and diastolic function, elevation of the anginal threshold in ischemic heart disease, and decreased morbidity and mortality in congestive heart failure. PMID- 1893646 TI - Treatment considerations for the hypertensive patient over age 55. AB - The prevalence of hypertension increases with age. The majority of the hypertensive population is over age 55. Although the treatment of systolic hypertension remains incompletely understood, the reduction of diastolic hypertension with pharmacotherapy has been shown to reduce complications from hypertension in persons over age 55. The older hypertensive patient is at risk for the same complications as the younger patient: angina, myocardial infarction, arteriosclerosis obliterans, stroke, myocardial hypertrophy, congestive heart failure, and renal failure; the risk of sudden death and multi-infarct dementia in the older patient may be somewhat higher. The older hypertensive individual may have reduced plasma volume and defective salt and water conservation, reduced renal function, impairment of baroreceptor reflexes and sympathetic reactivity, and altered drug pharmacokinetics, or may have arteriosclerosis leading to pseudohypertension. Many circumstances interfere with adequate compliance with therapeutic regimens among the elderly. Concomitant medical conditions increase the possibility of drug interactions and require that the practitioner be able to adjust the antihypertensive program to the patient. PMID- 1893647 TI - The use of benazepril in hypertensive patients age 55 and over. AB - Benazepril, a newer angiotensin-converting enzyme inhibitor, has been evaluated for the treatment of mild to moderate hypertension in patients 55 years of age and older. The results of the clinical trials conducted to date indicate that benazepril provides effective antihypertensive therapy in this population, with efficacy comparable to that demonstrated in younger patients. Benazepril does not produce precipitous decreases in diastolic blood pressure following the initial dose, and is well tolerated by the elderly. It has a safety profile similar to that of placebo and generally better than that of hydrochlorothiazide. PMID- 1893648 TI - Blood pressure and heart rate of the preterm newborn following delivery. AB - Thirty-five preterm newborns were studied to determine the mean blood pressure and heart rate of preterm newborns less than 1500 gm and greater than or equal to 1500 gm at birth. Systemic blood pressure increased and heart rate decreased with increasing maturity at birth. Both systemic blood pressure and heart rate increased during the four days following delivery. The 95% prediction limits of stable preterm newborns less than 1500 gm and greater than or equal to 1500 gm at birth are useful criteria to define hypertension and hypotension, as well as tachycardia and bradycardia. PMID- 1893649 TI - Reversible lactose malabsorption and intolerance in Graves' disease. AB - Ten patients with untreated Graves' disease underwent tests to determine lactose absorption, liquid gastric emptying, and oral cecal transit time. To determine the influence of thyroid hormone status on lactose absorption, eight of these same patients had repeat studies when rendered euthyroid. Two of these eight patients also underwent studies while transiently hypothyroid. Motility studies were also evaluated in a group of 11 control subjects. Lactose malabsorption occurred in nine patients with Graves' disease. In seven patients who repeated these studies, lactose malabsorption normalized in three, symptoms induced by lactose improved in two and were unchanged in two. However, these latter two patients appeared to have improved symptoms in the transient hypothyroid state. Liquid gastric emptying was significantly faster in untreated patients than controls and treated self-same patients. Transit time was significantly faster in untreated patients than when they were rendered euthyroid. There may be a relationship between altered lactose absorption states and changes in intestinal motility in patients with Graves' disease. PMID- 1893651 TI - Symposium: Ambulatory blood pressure monitoring--an emerging technology. Toronto, Ontario, February 9, 1990. PMID- 1893650 TI - Introduction: ambulatory blood pressure monitoring--an emerging technology. PMID- 1893652 TI - Assessment of ambulatory blood pressure recorders: accuracy and clinical performance. AB - There are now more than ten different manufacturers of non-invasive, portable blood pressure monitors in North America, Europe, and Japan. These ambulatory blood pressure recorders measure blood pressure by either auscultatory or oscillometric methodology. Technologic advances in the recorders have resulted in reduction in monitor size, reduction in or absence of motor noise during cuff inflation, ability to program the recorder without an external computer system, and enhanced precision. Recently, there has been concern that more structured validation protocols have not been implemented prior to the widespread marking of ambulatory blood pressure recorders. There is a need for proper assessment of recorders prior to use in clinical research or practice. Data on several existing recorders suggest that while most are reasonably accurate during resting measurements, many lose this accuracy during motion, and clinical performance may vary among the monitors. Validation studies of ambulatory recorders should include comparison with mercury column and intra-arterial determinations, resting and motion measurements, and assessment of clinical performance in hypertensive patients. PMID- 1893653 TI - Clinical applications of ambulatory blood pressure monitoring: the white coat syndrome. AB - The estimation of an individual's true blood pressure by conventional clinical measurement is subject to a number of errors, stemming partly from the inherent variability of blood pressure, and also from the white coat syndrome, which is an elevation of blood pressure limited to the clinic setting. This may occur in about 20% of patients with mild hypertension, and is hypothesized to be a learned or conditioned response. Ambulatory monitoring may help to identify such patients. Other potential clinical applications of the technique include evaluation of patients with resistant hypertension, with excessively labile blood pressure, or with autonomic insufficiency, which may be characterized not only by hypotensive episodes, but also by hypertensive episodes during the night. An unresolved question is the definition of the upper limit of normal ambulatory pressure, which is required before ambulatory monitoring finds wide clinical acceptance. PMID- 1893654 TI - Patient and environmental factors affecting ambulatory blood pressure monitoring. AB - Several patient and environmental factors may limit the applicability of ambulatory BP monitoring. In children and in elderly patients, erroneous readings may occur more frequently. Comparison of 25 elderly (greater than 65 yr) vs 25 young subjects recently monitored for clinical reasons in our hypertension clinic showed slightly higher error rates (19% vs 15% of readings) in the elderly but similar willingness to undergo monitoring again (96% vs 84% of subjects, respectively). The technique has not been well validated in obesity. Arrhythmias may prevent currently available ambulatory BP machines from obtaining usable readings. Monitoring may prove unsatisfactory for patients engaged in physically active occupations, travelling in automobiles, or in environments where the noise of the ambulatory BP machine would be disruptive. Portable automatic monitors can detect abnormally elevated average BP during sleep but the diagnostic value of this pattern remains unknown. It is concluded that ambulatory BP monitoring may be successfully performed in most patients. PMID- 1893655 TI - Ambulatory blood pressure and target organ involvement in hypertension. AB - Casual (or office) blood pressure values have been shown to be associated with cardiovascular morbidity or mortality in a variety of prospective trials assessing cardiovascular risk. In recent years, however, controversies have developed regarding the capacity of casual blood pressures to predict cardiovascular risk in an individual patient with high blood pressure. Prospective, cross-sectional studies have been performed in several centres that compare the capacity to predict hypertensive target organ involvement by casual vs 24-h mean, awake, or sleep blood pressures. Ambulatory blood pressure has been consistently superior to casual blood pressure in predicting target organ involvement in hypertension. As most of the data collected to date has involved cardiac studies, however, fewer conclusions can be drawn regarding renal and cerebrovascular disease. With regard to cardiac structure and/or function, ambulatory blood pressure is much more useful than casual blood pressure in determining the likelihood of an abnormal index in an individual patient with hypertension. PMID- 1893656 TI - Will knowing the variability of ambulatory blood pressure improve clinical outcome? An additional consideration in the critical evaluation of this technology. AB - The range through which blood pressure varies from moment to moment and from wakefulness to sleep confounds the assessment of the patient with suspected hypertension. The clinical application of this information depends upon the needs and resources available to the physician. Awareness of the variance between average clinic and average ambulatory blood pressures, acquired by ambulatory monitoring, may influence diagnostic and therapeutic decisions to the benefit of the patient. However, the hypothesis that those 20-30% of patients referred for management of mild to moderate hypertension after initial screening who are normotensive when remote from the clinic environment do not require treatment has not been tested prospectively. Two studies using intra-arterial recordings and one large study using a non-invasive device have demonstrated a relationship between ambulatory blood pressure variability and cardiovascular consequences of hypertension that is independent of the level of arterial pressure. Loss of information and problems with accuracy during activity preclude similar calculations of blood pressure variability by currently available portable non invasive recorders. The hypothesis that actions based upon knowledge of blood pressure variability can improve clinical outcome is attractive, but waits, for its confirmation, large and rigorous trials based on advances in technologic capabilities that will permit accurate, continuous, yet non-invasive monitoring of ambulatory blood pressure. PMID- 1893657 TI - Prospective study of ambulatory monitoring and echocardiography in borderline hypertension. AB - This study was done to evaluate prospectively whether ambulatory blood pressure recordings (AMB) (Spacelabs) would more accurately predict increases in left ventricular mass (LVMI) than did blood pressures measured by a nurse in the absence of a physician, using a random zero sphygmomanometer (RZ) and an automated oscillometric digital device (BPI). One hundred patients being followed by their family physician with a diagnosis of borderline hypertension with at least two office diastolic readings of 90-100 mmHg were studied at baseline and every six months for two years with RZ, BPI, and AMB; echocardiography was repeated annually. Over sixty percent of the patients were normotensive in the research unit by AMB, BPI, and RZ at entry. At entry 24% of patients had increased LVMI greater than 110 g/m2 (left ventricular enlargement, LVE) and at 2 years 32% had LVE. Stepwise linear regression was used to determine which measurement was most predictive of LVE at two years. It showed that the most predictive were baseline echo LVMI and BPI systolic pressure. These two variables predicted 45% of the risk with no other variables contributing significantly. However, when BPI was removed, AMB systolic pressure contributed significantly, though the strength of prediction was reduced to 40%. In a subset of 40 patients who underwent mental stress with mental arithmetic and mirror tracing, the magnitude of systolic pressure elevation during mental stress correlated significantly with LVE over 2 years (R = 0.54, p less than 0.001). PMID- 1893658 TI - A review of the stability of ambulatory blood pressure: implications for diagnosis of hypertension. AB - Ambulatory BP monitoring by obtaining many measurements on one day might eliminate the need for multiple visits on different days to diagnose hypertension. However, review of the published literature shows the stability of ambulatory BP as assessed by test-retest correlation between days to be similar to that of office BP in research settings: r = 0.87/0.70 vs 0.79/0.71 (systolic/diastolic). Between-day standard deviations of the difference are also similar: 8/7 mmHg vs 9/7 mmHg, respectively. The reproducibility of within-day fluctuation in BP is poor (r = 0.28/0.11) and may account for some of the difficulty in showing correlations between BP variability and target organ damage. Evidence to date suggests that ambulatory BP monitoring will not reduce observed between-day differences in BP. Diagnosis of elevated BP will require repeated visits whether office or ambulatory BP measurement is employed. PMID- 1893659 TI - Ambulatory blood pressure monitoring and the primary care physician. AB - The primary care physician welcomes technology that will reduce overlabelling and overtreatment of hypertension. Three concerns with respect to ambulatory blood pressure monitoring are: the clear identification of those patients who will benefit from monitoring; the potential for labelling patients prematurely as having technical abnormalities (i.e., 'hypervariability'), which may have little clinical significance; and the inaccessibility of ambulatory monitoring. To determine patient acceptance of ambulatory monitoring, a follow-up survey of 37 patients who used the Spacelab 5200 device was conducted. Twenty-four percent said they would not be agreeable to further monitoring. While newer devices may be less disruptive, the point is made that it is important to include patient assessments in the evaluation of these devices. A comparison is undertaken between ambulatory monitors and the more accessible self-monitoring devices which involve the patient to a greater degree in his/her own care. PMID- 1893660 TI - Assessment of antihypertensive treatment by ambulatory blood pressure monitoring. AB - Whole-day ambulatory blood pressure monitoring provides a better diagnosis of hypertension and a better prediction of long-term cardiovascular complications than conventional office measurements. Ambulatory monitoring is a reliable technique for the assessment of antihypertensive drugs. First, it determines truly hypertensive patients in whom treatment is appropriate. Second, ambulatory blood pressure monitoring helps to evaluate the efficacy of antihypertensive therapy during average working days. Finally, this method allows investigators to establish the duration of antihypertensive activity of new drug formulations, and thereby to improve compliance. PMID- 1893661 TI - Measuring the adverse effects of unnecessary hypertension drug therapy: QALYs vs HYE. AB - Avoiding the adverse effects of unnecessary drug therapy is one of the key objectives of those who advocate the use of ambulatory blood pressure monitoring (ABP). The use of a proper outcome measure to assess the effect of drug therapy on patients' lifetime quality of life is clearly of great importance. The purpose of this paper is to alert readers that the use of quality-adjusted life-years (QALYs) gained as a measure of outcome is likely to underestimate such effects. Another outcome measure is suggested, that of healthy years equivalent (HYE), which enables respondents to reveal their true range of preferences. A study is called for which involves actual measurement of individual preferences and uses the more powerful and sensitive measure of outcome (HYE). PMID- 1893662 TI - [Clinical studies of 23 patients with multiple system atrophy presenting with vocal cord paralysis]. AB - In order to elucidate the clinical features and the prognosis for life in the patients with multiple system atrophy (MSA) presenting with vocal cord paralysis (VCP), we studied the correlation between VCP and other neurological findings including cerebellar, pyramidal, extrapyramidal and autonomic nervous signs. Subjects were 48 MSA patients: 23 with VCP and age- and illness duration-matched 25 without VCP. MSA in this paper comprised clinically Shy-Drager syndrome, olivopontocerebellar atrophy, and striatonigral degeneration. MSA patients with VCP had in general more severe neurological findings, compared with those without VCP. Urinary incontinence developed in the relatively early stage of illness and preceded VCP in all patients. VCP developed not only in far-advanced stage but at any time in the course of illness. As to swallowing function when a diagnosis of VCP was established, about half of the patients with VCP needed nasogastric tube feeding and the remaining half tolerated oral feeding. VCP correlated strongly with urinary incontinence but not always with the severity of orthostatic hypotension or extrapyramidal tract sign such as parkinsonism. Five of the eight patients without tracheostomy came to sudden death. The mean duration from making a diagnosis of VCP to death was 1.1 years. In contrast, nine of the 11 patients with tracheostomy were alive and the survival periods after tracheostomy reached a maximum, five years. These facts suggest that the prognosis for life in the patients with VCP depends in part upon whether tracheostomy was carried out or not.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1893663 TI - [Clinical analysis of myasthenia gravis accompanied by invasive thymoma]. AB - Over the last 20 years, 6 patients with myasthenia gravis and invasive thymoma have been seen in our Department. These patients underwent non-total excision cases. This represents 2.5 percent of 242 myasthenia gravis patients in our series. We can see 17 such patients in the literature in Japan including our cases. The age ranged 20 to 77 years and the ratio of male to female was 10:7. Post-operative therapeutic methods for invasive thymoma included irradiation, steroid therapy and combination chemotherapy. Every method showed good therapeutic results, but steroid therapy and chemotherapy showed especially good therapeutic effects in the early stage of the disease. Though these therapeutic effects were better than those obtained in other malignant tumors, thymomas tended to reappear within several years, when tumors showed no response to any therapeutic method. It is well known that steroid therapy reduces the level of antiacetylcholine receptor antibody, whereas chemotherapy also reduces antiacetylcholine receptor antibody. Over all 5-year survival rate was 53%, and the 10-year survival rate was 29%. Three out of 6 cases of death were due to myasthenic crisis (50%) and 2 out of 6 cases were due to invasive tumor itself (38%). These results suggested that total excision of the thymoma, if possible, and for the remaining tumor, high doses of adrenocorticosteroids and combination chemotherapy seem to be treatments of choice. PMID- 1893664 TI - [Effects of antiepileptic drugs on delivery and early childhood--comparison among mono-therapies of valproic acid, phenytoin, carbamazepine and phenobarbital]. AB - The effects of antiepileptic drugs (AED) on infants during pregnancy and delivery were studied in a total of 82 epileptic mothers on various monotherapies; 29 cases receiving valproic acid (VPA), 20 receiving phenytoin (PHT), 18 on carbamazepine (CBZ) and 15 on phenobarbital (PB). While AED serum concentrations were low in most cases of VPA, PHT and PB except for one case of VPA which exceeded therapeutic limits, concentrations were within therapeutic levels in many cases of CBZ. CONCLUSION: When compared with normal controls, abnormal deliveries such as caesarian section were seen more frequently in epileptic mothers under AED treatment. In addition, infants in PB cases were shown to have significantly lower mean birth length, weight and head circumference, suggesting that PB may retard fetal growth. The incidence of malformation in cases of VPA, PHT, CBZ and PB, was 10.3%, 5.0%, 0% and 6.7%, respectively. There were five types of malformation: in VPA cases, spina bifida, Siamese twins and ventricular septal defect tended to be severe, while in PHT and PB cases, cor biloculare and hypospadias respectively were observed. In cases of VPA, serum levels in the umbilical cord were found to be 150% higher than those in the mother. PMID- 1893665 TI - [Asymptomatic cerebral hemorrhage detected by MRI]. AB - Detection of previous cerebral infarction on CT films of patients with no history of stroke is a common occurrence. The incidence of silent cerebral infarction was reported to be about 10 to 11 percent, but very few reports concerning asymptomatic cerebral hemorrhage available. However, recent clinical application of MRI has resulted in the detection of old asymptomatic hemorrhage in patients with no history of known stroke-like episodes. The purpose of this study was to elucidate the incidence, the cause and the character of the asymptomatic cerebral hemorrhage among patients who had undergone MRI examinations. From September 1987 till June 1990, 2757 patients have undergone 3474 times of MR scan of the brain with 1.0 Tesla Siemens Magneton unit in our hospital. 17 patients showed no clinical signs or symptoms suggesting a stroke episode corresponding to the detected hemorrhagic lesion. Seventeen patients correspond to 0.6% of the patients who underwent MRI, 1.5% of the patients with cerebrovascular disease and 9.5% of the patients with intracerebral hemorrhage, which was rather higher than expected. Among the 17 patients, 12 were diagnosed as primary ICH and 5 as secondary ICH. Most of the primary asymptomatic hemorrhages were hypertensive ones and slit-like curvilinear lesions between the putamen and claustrum or external capsule. The secondary asymptomatic hemorrhages were due to AVM and angiomas in the frontal cortex, thalamus and pons. PMID- 1893666 TI - [Long-term changes in cerebral blood flow in patients with atherothrombotic and embolic brain infarction]. AB - Cerebral blood flow (CBF) was measured twice at years interval using xenon-133 inhalation technique in patients with atherothrombotic and embolic supratentorial brain infarction. The purpose of the study was to elucidate factors influencing long-term change in CBF in two subtypes of brain infarction of different mechanisms. Those patients were excluded from the study, who had bilateral hemispheric lesions, significant arterial lesion in the contralateral carotid axis and recurrent stroke before the second measurement of CBF. Of 46 patients studied, 23 (17 men and 6 women) were classified as atherothrombotic and 23 (15 men and 8 women) as embolic infarction based on the diagnostic criteria reported earlier. Their age at onset was 60.6 +/- 8.9 years old (mean +/- S.D.) for atherothrombotic patients, and 60.2 +/- 11.0 years old for embolic patients. The first measurement of CBF was performed between 31 and 87 days and the second measurement between 13 and 99 months after onset. In atherothrombotic group, mean hemispheric CBF (mCBF) of the affected side tended to be higher in patients examined at intervals shorter than 30 months, but tended to decrease in those at longer interval. The multivariate stepwise regression analysis indicated only "the interval between 2 measurements" to have a significant effect on reduction of mCBF, although in addition to the interval (p less than 0.05), infarct-size (p less than 0.01) and change in PaCO2 (p less than 0.05) were suggested to be possible factors by single regression analysis. In embolic group, an increase in hematocrit had a significant effect on reduction of mCBF, even when being evaluated with multivariate stepwise regression analysis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1893667 TI - [Two long-living brothers of dystrophin-related muscular dystrophy with an in frame deletion of exon 3 of the dystrophin gene--clinical features and diagnosis]. AB - Two long-living brothers of dystrophin-related muscular dystrophy with an in frame deletion of exon 3 of the dystrophin gene were described. Weakness of the lower extremities and pseudohypertrophy of calf muscles began at the age of 2 years in the elder brother and 4 years in the younger brother, respectively. Clinical symptoms progressed rapidly and both of them lost ambulation and became wheelchair bound at the age of 11-12 years. However, the progression of the disease process slowed in late teens, and now at the age of 36 and 33 years, respectively, they do not have respiratory or cardiac insufficiency, although they are disabled severely. Southern blotting with the entire dystrophin cDNAs, cDNA 1-2a, 2b-3, 4-5a, 5b-7, 8, and 9-14, revealed a single deletion of exon 3 in the 2 brothers. The mother was shown to be a heterozygote for this mutation. The unique clinical features of these brothers were presumed due to the following 2 factors: (1) a single deletion of exon 3 is an in-frame deletion of the dystrophin gene, and (2) exon 3 corresponds to a unique domain of the dystrophin molecule; the amino-terminal region which is highly homologous to the actin binding-region of alpha-actinin. We consider that these 2 brothers are compatible with the so-called frame-shift hypothesis of Duchenne/Becker muscular dystrophy (DMD/BMD) phenotype, although they are diagnosed DMD by the classification method based on the patients' age of becoming permanently wheelchair bound. PMID- 1893668 TI - [A case of Kennedy-Alter-Sung syndrome with type IIa hyperlipidemia--study on sex hormone receptor and lipid metabolism]. AB - A 57-year-old man of Kennedy-Alter-Sung syndrome (K-A-S) with type IIa hyperlipidemia was reported with studies of several sex hormone receptors. He noticed tremulous movements of hands on gripping at age 40 and gynecomastia at age 46. He had been pointed out to waddle since 52 years old, and also noticed difficulty in going up stairs and standing up at age 54. He was admitted to our Neurology Service on June 5, 1989. On general physical examinations, gynecomastia, eyelids xanthomas and hypertrophy of Achilles tendons were found. Neurologic examination revealed clear consciousness and slight dysarthric speech with nasal voice. Cranial nerves showed mild bilateral facial weakness, poor uvula and soft palatal movements, atrophy and weakness of bilateral sternocleidomastoid muscles, and atrophy of tongue with fasciculation. The four extremities were hypotonic, and proximal muscular atrophy and weakness of four extremities were seen. Deep tendon reflexes were absent in four extremities and fasciculation on both thighs was noted on contraction. Sensory and cerebellar functions were intact. Waddling gait and Gowers' sign were present. In K-A-S syndrome, abnormal lipid metabolism such as a family of type IIa hyperlipidemia, or familial and sporadic cases of type IV hyperlipidemia has been documented. In the family of our cases, his elder sister was found to have type IIa hyperlipidemia, while his son had type IV hyperlipidemia. The coexistence of these two types of hyperlipidemia in the same family of K-A-S syndrome has not been reported so far to our knowledge.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1893669 TI - [Motor impairment in amyloid-associated muscle pseudohypertrophy]. AB - Muscle involvement, usually associated with pseudohypertrophy, has been described very rarely in patients with AL-(primary or myeloma-associated) amyloidosis. Although precise mechanisms for the motor impairment in amyloid-associated muscle pseudohypertrophy are unknown, amyloid accumulation in the muscle has been thought to be a main cause of muscle weakness. We here describe a patient of amyloid-associated muscle pseudohypertrophy with IgA lambda plasma cell dyscrasia, and discuss possible mechanisms for the physical disability. The patient, a 65-year-old man, was admitted because of progressive stiffness of limb and bulbar muscles for approximately three years. On physical examination he appeared muscular and athletic. The muscles were firm with wooden or rock-like hardness. Superficial veins were engorged in all extremities. Macroglossia was marked. Resistance to passive movement was noted in all extremities with decreased range of motion; proximal joints were more severely affected. The patient walking for a short distance, his legs became heavy, tired and firm, which forced him to stop. Immunoelectrophoresis revealed the monoclonal secretion of IgA lambda in the serum and free lambda light chain in the urine. Bone marrow examination disclosed 30% plasma cells with a large prevalence of IgA lambda containing cells. A bone scan showed an increased uptake of 99mTc-methylene diphosphate in the shoulder and pelvic joints. Tissue pressures of the quadriceps femoris at the supine and standing positions, and after walking were as high as 47, 89, and 112 mmHg, respectively. Venography of the left leg showed narrowing of the femoral vein and visualization of saphena magna vein.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1893670 TI - [A case of HTLV-1 associated myelopathy progressed in course over 30 years]. AB - A 66-year-old female suffering from HTLV-1 associated myelopathy (HAM) for more than 30 years was hospitalized because of memorial impairment, deafness, dysarthria, dysphagia, and complete paraplegia. She first noticed stiffness and weakness of the right leg at 35 years of age. Gait disturbance was slowly progressed and complete paraplegia developed 18 years later. Neurological examinations on admission revealed that she was bedridden with decubitus, mental deterioration (pre-dementia of subcortical type), bilateral optic nerve atrophy, severe sensory-neural deafness, dysarthria, complete paraplegia, and marked neurogenic bladder. Laboratory data showed mild normocytic anemia and moderate diabetes mellitus. Anti-HTLV-1 antibody titers in serum and CSF were 78,192X and 1,024X, respectively (PA method). Serum levels of soluble IL-2 receptor was markedly elevated (2,200 U/ml). Peripheral blood lymphocytes showed spontaneous proliferation when cultured for 5 days (3H-thymidine uptake; 45,285 cpm/5 X 10(4) cells). MRI examinations of the spinal cord disclosed a predominant atrophy of lower thoracic cord without any compressive lesions. Brain MRI showed diffuse high intensity lesions of the periventricular area on T2 weighted images. Such abnormalities were predominantly found in fronto-parietal region and were quite similar to those of leuko-ariosis. Single photon emission CT using 123I iodoamphetamine showed hypoperfusion of cerebral white matter on delayed image. It has been reported that intellectual impairment and brain atrophy are not usually seen in HAM patients. The present case, however, shows that such abnormalities of the central nervous system could occur in HAM patients with a long duration of illness. PMID- 1893671 TI - [Juvenile parkinsonism in monozygotic twins]. AB - A pair of monozygotic twins concordant for juvenile Parkinsonism are described. These twin sisters have lived together until 18 years old. Twin A noted tremor in the right hand and right-sided stiffness and slowness at the age 20. Initially, a marked improvement was shown with L-dopa treatment. However, one year after the beginning of treatment, dopa-induced dyskinesia appeared. Twin B noted tremor and right-sided stiffness and basal ganglia calcification in both patients. These twin patients suggest that genetic factors may play an important role in the cause of juvenile Parkinsonism. PMID- 1893672 TI - [Chronic inflammatory demyelinating polyradiculoneuropathy presenting localized radiculopathy as an initial symptom]. AB - We reported a patient with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), presenting localized radiculopathy as an initial symptom. The patient, a 38-year-old man, developed muscle atrophy of right shin and calf. In April 1988, neurological examination revealed decreased superficial sensation and muscle atrophy in right L-4 distribution. MRI of the lumbar spinal cord and myelography were negative. In April 1989, he was admitted to Chiba University Hospital. There were slight weakness of right ankle extension and flexion, muscle atrophy of bilateral shin and calf (that of the right leg was more marked), decreased sensation of polyneuropathy type in all modalities and generalized hypo- or a-reflexia. Nerve conduction study revealed marked prolongation of F response and focal conduction block in various site. The CSF was acellular and total protein was 177 mg/dl. Sural nerve biopsy disclosed decreased number of large myelinated fibers and scattered thin myelinated fibers. This case indicates that CIDP may present localized radiculopathy in early phase and is important to point out various mode of onset among CIDP. PMID- 1893673 TI - [Analysis of hemiparesis with homolateral ataxia by single photon emission CT]. AB - Case 1. A 46-year-old man suddenly developed mild gait disturbance and left hemiparesis. On examination, gross strength was slightly reduced in the left extremities. The finger-to-nose and heel-to-knee tests disclosed moderate dyssynergia and dysmetria on the left side that could not be explained by the muscular weakness. Deep tendon reflexes were more brisk in the left extremities. There was no Babinski sign. Magnetic resonance imaging showed a region of high signal intensity in the right posterior limb of internal capsule with extension into lateral thalamus. The lesion involved the cortico-ponto-cerebellar pathway and partly the dentato-rubro-thalamo-cortical pathway. No lesions were seen in the brainstem. Single photon emission CT with 123I-IMP showed left cerebellar hypoperfusion termed crossed cerebellar diaschisis by Baron et al. Case 2. A 65 year-old female developed weakness of the left extremities and gait disturbance. On examination, there was a horizontal nystagmus on lateral gaze to each side. She showed dysarthria, mild left hemiparesis and slight left hypesthesia. The finger-nose and heel-knees tests revealed moderate dysmetria and dyssynergia on the left side. Deep tendon reflexes were hyperactive in the left extremities with left Babinski sign. CT showed a low density area in the right basis pontis at about middle level. Intravenous digital subtraction angiography revealed a slight stenosis of right vertebral artery, but no other abnormality. The lesion involved the cortico-ponto-cerebellar pathway. Single photon emission CT with 123I-IMP showed left cerebellar hypoperfusion. The right cerebellar blood flow was normal.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1893674 TI - [Cystinuria with symptoms of cerebellar atrophy--a case report]. AB - We report cystinuria and symptoms of cerebellar atrophy in a 45-year-old man. His parents were first cousins, and many members of his family had stones of urinary tract or gait impairment. Neurological examination disclosed cerebellar signs resembling those of spinocerebellar degeneration. Urinalysis disclosed high cystine, lysine, ornitine and arginine output. Cystine was 1153.8 micro mol/day (normal range, 22-170); lysine, 3443.9 (normal range, 44-1000); ornitine, 283.8 (normal range, 7-40); and arginine, 154.0 (normal range, 9-50). Neurological complications reported to be associated with cystinuria include mental retardation, muscular dystrophy, hypotonia and dwarfism, mongolism, paroxysmal dyskinesia, myopathy, migraine, spastic paraplegia, multiple sclerosis, subacute combined degeneration and cranial polyneuropathy. Cerebellar signs have been reported in only two cases, and to our knowledge, this is the first case of cystinuria with cerebellar atrophy ever reported. Some common metabolic errors may have caused both disorders, although they also may have developed independently. PMID- 1893675 TI - [A case of measles meningoencephalitis with marked increase of plasma cells in cerebrospinal fluid]. AB - Marked increase of plasma cells in cerebrospinal fluid (CSF) was observed in a 22 year-old female patient with measles meningoencephalitis. Typical measles exanthema was followed, 3 days later, by neurological abnormalities such as confusion, severe meningeal signs and bilateral pyramidal signs. Immunological examination showed slight elevation of IgG, normal T cell subsets and NK cell activity in peripheral blood. The antibody titer of measles was 32x in serum (4x after 2 months). CSF contained 167 cells/mm3, 66% of which was plasma cells. Total protein was 75 mg/dl, and IgG (24.5 mg/dl) showed high values. The antibody titer of measles was 4x (1x after 2 months). The antibody index was 7.15 (N = 2). The anti-myelin antibody was 8x. Oligoclonal band in CSF was negative. The appearance of large number of plasma cells in CSF in viral meningoencephalitis is extremely rare in the literature. However, B cell activation in peripheral blood in measles encephalitis has been reported. Therefore, immunologically abnormal findings in CSF of this case suggest marked B cell activation occurring in the central nervous system in measles meningoencephalitis. PMID- 1893676 TI - [A case of multiple sclerosis with syrinx formation demonstrated on MRI]. AB - A 26-year-old woman developed two separate episodes of myelopathy mainly presenting paraparesis. Neurologic examination disclosed flaccid paraparesis associated with slight spasticity of the right arm. Deep tendon reflexes were generally hyperactive with positive bilateral Babinski and Chaddock reflexes. Arm pronation sign and Barre leg signs were bilaterally positive. Sensory disturbance below T6, and diminished vibration and position sense in both legs were seen. Urinary and fecal disturbances were also present. She could walk, but her gait was unsteady. Brain MRI showed abnormal high signal intensity areas on T2 weighted image at the left fronto-parietal lobe and right temporo-parietal lobe. Spinal MRI disclosed a cavity formation which was delineated low signal intensity on T1-weighted image through T4 to T8 and high signal intensity on T2-weighted image through T3 to T10. From these clinical manifestations and radiological findings, she was able to be diagnosed to have definite MS. The coexistence of syrinx formation in MS has rarely been reported, and only 5 cases including our case were found. These cases are characterized by the central localization of syrinx, and fair prognosis in their neurological features. PMID- 1893677 TI - [Morel's laminar necrosis like findings on MRI in a case of extra-pontine myelinolysis]. AB - A 39-year-old man developed disturbance of consciousness with hyponatremia during the treatment of schizophrenia in another hospital. He became alert after the correction of hyponatremia. But his consciousness deteriorated one day later in spite of normal serum sodium level, then he was referred to our hospital. The disturbance of consciousness, quadriparesis and rigidity were persisted even 4 months later. MRI (T2WI) showed well defined high intensity areas along the deep layer of the cerebral cortex and in the bilateral basal ganglia. But there were no lesions in the pons on MRI. Therefore, the diagnosis was made as extra-pontine myelinolysis (EPM) without apparent central pontine myelinolysis (CPM) according to the MRI findings. Recently, the EPM without CPM has been reported in 3 patients. Two cases were examined pathologically, findings of which were characterized by Morel's laminar necrosis at the deep layer of the cerebral cortex. But there is no report in the literature describing the detection of Morel's laminar necrosis on antemortem MRI. It seemed that the MRI findings of our case indicated Morel's laminar necrosis. Our case is suggestive in relation to the pathogenesis of EPM and CPM. PMID- 1893678 TI - [A case of retrosplenial amnesia]. AB - A case of retrosplenial amnesia was reported. The patient was an 81-year-old right-handed male. He developed amnesic syndrome following cerebral infarction situated left retrosplenial region. His immediate memory was preserved. Recent memory for both verbal and nonverbal modalities was disturbed. He also showed retrograde amnesia for 2 years. The is the first report of retrosplenial amnesia in Japan. We should take into account of the retrosplenial region as a causative site of amnesic syndrome. PMID- 1893679 TI - Initial circulatory responses to changes in posture: influence of the angle and speed of tilt. AB - To assess if changes in the angle or speed of tilt could account for the differences between the initial (first 30 s) circulatory responses induced by active and passive changes in posture, as found in previous studies, we investigated the initial heart rate and blood pressure responses induced by stand up from supine and various head-up tilt manoeuvres in 12 healthy, male subjects. Comparison was made between 70 degrees head-up tilt in 3 s, 90 degrees head-up tilt also in 3 s and 70 degrees head-up tilt in 1.5 s, using an automatic pneumatic-driven tilt table with foot support. It was found that the initial heart rate and blood pressure responses induced by the three tilt manoeuvres were almost identical in time course and amplitude, but significantly different from those induced by stand up. The results of this study prove that regardless of the angle and speed of tilt, the initial circulatory responses induced by passive changes in posture are essentially different from the responses induced by active changes in posture. PMID- 1893680 TI - Circulatory responses to stand up: discrimination between the effects of respiration, orthostasis and exercise. AB - The initial circulatory responses to an active change in posture (stand up from supine) were compared with the responses induced by a passive change in posture (head-up tilt) and a burst of muscular exercise on a bicycle ergometer (upright cycling) in order to differentiate between exercise- and orthostasis-induced effects. In eight subjects heart rate responses and in four subjects intra arterial pressure transients were measured. In addition the effects of respiration on heart rate responses to the three manoeuvres were assessed. Both stand up and cycling induced almost superimposable and pronounced heart rate responses lasting for about 30 s. This contrasts with the more gradual increases following head-up tilt. Changing the respiratory phase during the performance of the manoeuvres exerted its effect on heart rate responses in the first 5 s only. Like stand up, cycling induced a transient blood pressure fall lasting for 30 s on average. As both manoeuvres were performed during inspiration the transients observed are not caused by involuntary Valsalva straining. In conclusion, the maximum and duration of the heart rate responses induced by stand up, cycling and head-up tilt are not influenced by respiratory activity. The initial fall in blood pressure following stand up is probably the result of the muscular effort of the manoeuvre and not due to the effects of orthostasis or Valsalva straining. PMID- 1893681 TI - Deep venous valvular function assessed with intramuscular pressure recording. AB - Intramuscular pressures were measured in the anterior tibial muscle with the microcapillary infusion method in 10 patients (11 limbs) with deep venous valvular insufficiency. The results were compared with pressure measurements in healthy controls (n = 8) and in patients with only superficial venous insufficiency (n = 7). The technique could differentiate patients with deep venous reflux from patients with superficial venous reflux and healthy controls. In contrast to the other two groups studied, patients with deep venous reflux were characterized by a small decrease of muscle relaxation pressure during exercise followed by a short recovery time. The method described provides a potential for evaluating regional deep venous valvular function. However, besides deep venous reflux other factors such as rate of arterial inflow, venous capacity and muscle pump function also might influence the results obtained with intramuscular pressure recordings. PMID- 1893682 TI - The effect of cooling on toe systolic pressures in subjects with and without Raynaud's syndrome in the lower extremities. AB - The effect of changes in local and body temperature on the toe systolic pressures was studied in 20 subjects with and 30 without Raynaud's syndrome in the toes. The pressures were significantly lower in the group with Raynaud's syndrome under all experimental conditions (P less than 0.01). The pressures were significantly lower during body cooling than during body warming in both groups (P less than 0.01). The mean decrease with body cooling was 58 mmHg in the group with Raynaud's syndrome and 24 mmHg in the control subjects (P less than 0.01). During body cooling pressures fell to less than 30 mmHg in 70% of subjects with Raynaud's syndrome and in 3% of the controls. Local cooling from 30 to 10 degrees C during body cooling resulted in a significant mean decrease in pressure of over 40 mmHg in both groups (P less than 0.01) and the pressure fell below 30 mmHg in over 90% of the group with and in 26% of those without Raynaud's attacks. The results indicate the importance of body cooling and local temperature in the mechanism of vasospasm in the toes. They are also relevant to the diagnosis of Raynaud's syndrome in the lower limbs and have implications for the testing of patients with arteriosclerotic occlusion since erroneously low pressure values could be obtained in tests when the feet are cold. PMID- 1893683 TI - Effects of vacusac in intermittent claudication: a controlled cross-over study. AB - The effect of a new physical treatment modality, Vacusac, was tested on a group of patients with stable intermittent claudication. Twenty-two patients with a median age of 65 years and a median duration of intermittent claudication of 5 years were randomized to either active or placebo treatments. Seventeen patients completed the study. The effect of treatment was quantified by measurements of systemic and peripheral systolic blood pressures and by measurements of the pain free and the maximal walking distance on a treadmill. The ankle pressure index (ankle systolic pressure/arm systolic pressure) and toe pressure index (toe systolic pressure/arm systolic pressure) were calculated. After 25 active treatments, administered over a period of 2 months, the patients allocated to this group attained a significant increase in the pain-free walking distance from 54 m (24-107 m) to 99 m (30-420 m) (P less than 0.05) and in the maximal walking distance from 99 m (36-182 m) to 185 m (68-591 m) (P less than 0.05). The patient group receiving 25 placebo treatments did not show any significant changes in either the pain-free or the maximal walking distance. This group then received 25 active treatments over a period of 2 months. This active treatment resulted in a significant increase in the pain-free walking distance from 51 m (14-100 m) to 86 m (18-1000 m) (P less than 0.05) and in the maximal walking distance from 98 m (40-199 m) to 175 m (51-1000 m) (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1893684 TI - A morphometrical comparison of right and left whole human vastus lateralis muscle: how to reduce sampling errors in biopsy techniques. AB - In studies of the effects of different training programmes, one muscle--most commonly the vastus lateralis--is used for the experiment while the contralateral muscle serves as a control, at the same time as muscle biopsies are taken from both sides. In order to increase the reliability of such studies, the sources and the magnitude of the sampling errors in the biopsy techniques need to be assessed in detail. In this study, cross-sections of whole right and left vastus lateralis muscle from six young sedentary right-handed men were prepared, and the total number and size of fibres and the proportion of the different fibre types were calculated. A significant difference (P less than 0.05-P less than 0.001) between the right and the left muscle was found for at least one of the three variables in each of the six men, but there was no systematic difference and, therefore, no significant right-left difference for the whole group. The maximum difference between the right and the left side for the mean fibre size was 25% and for the fibre type proportion 5%; these differences are much smaller than the known variation within individual muscles. In conclusion, any study involving biopsies from both the right and the left vastus lateralis may use either muscle for the experiment while the contralateral muscle serves as a control without leading to systematic sampling error, whereas the errors involved in taking small samples from each muscle are much more important to control and to reduce. PMID- 1893685 TI - Cardiovascular autonomic reflex tests: normal responses and age-related reference values. AB - One hundred and forty-three healthy unmedicated subjects from a random sample, aged 20-80 years, were examined and cardiovascular autonomic function tests (Valsalva manoeuvre, deep and quiet breathing tests and active orthostatic test) were performed in order to study normal responses to these tests and to determine age-related reference values. Most of the cardiovascular indices reflecting autonomically mediated heart rate responses decline with advancing age and this leads inevitably to the need for age-related reference values. The indices are in general independent of sex but most indices are dependent on resting heart rate. The inter-individual variation is very marked so that the normal ranges are wide, and because the indices diminish with age, the lower reference values are less suitable for use in aged subjects. The reference values make it possible to use the indices for diagnostic purposes in young and middle-aged subjects (up to 65 years), whereas in older subjects the indices can be used in order to exclude autonomic disturbances. Reproducibility of heart rate indices is satisfactory or good whereas reproducibility of blood pressure indices is poor. PMID- 1893686 TI - Contact sensitization to 5-chloro-2-methyl-4-isothiazolin-3-one and 2-methyl-4 isothiazolin-3-one (MCI/MI). A European multicentre study. AB - The frequency of positive reactions to 5-chloro-2-methyl-4-isothiazolin-3-one and 2-methyl-4-isothiazolin-3-one (MCI/MI) were studied at 22 European contact dermatitis clinics over a period of 1 year. A total of 4713 patients participated. All the patients were patch tested with nickel sulphate, formaldehyde, paraben-mix, and MCI/MI. 19.4% of the patients had positive patch tests to nickel, making this the most common allergen. 3% of the patients reacted to 100 ppm MCI/MI, while 2.6% reacted to formaldehyde and 1.1% to parabens. There was great variation in the frequency of MCI/MI sensitivity among the 22 centres. MCI/MI contact allergy was most common among women and in patients with facial dermatitis, while it was rarely seen in patients with dermatitis on the lower legs. There were no fluctuations in the number of positive patch tests to MCI/MI on a monthly basis when the results from all centres were combined. 117 of the 141 MCI/MI sensitized patients included in the study were retested. 88% had positive patch tests when retested. 101 of the MCI/MI-sensitive patients participated in a double-blind, placebo-controlled product use test. This test showed that 31% of the MCI/MI-sensitive patients had a positive reaction to a MCI/MI-preserved product. Only a few patients reacted to a control product. It is concluded that the preservative MCI/MI is an important new contact allergen. PMID- 1893687 TI - The relationship between skin surface temperature, transepidermal water loss and electrical capacitance among workers in the fish processing industry: comparison with other occupations. A field study. AB - A field study among workers in the fish processing industry (n = 143) was performed to obtain information about skin surface temperature, transepidermal water loss (TEWL), and electrical capacitance and their relationships during work. The skin temperature, TEWL and electrical capacitance were measured on the fingers, hands and forearms. A linear positive relation was found between the temperature and TEWL (in all measured areas), a linear negative relation between the temperature and capacitance (fingers and palms), and a linear negative relation between the capacitance and TEWL (fingers). The results on the fingers among workers in the fish processing industry were compared with results among metal workers (n = 52), cleaners (n = 30), gut cleaners (n = 25), nurses (n = 16), office workers with indoor climate syndrome (n = 20) and normal controls (n = 29). A linear positive relation was found between the respective temperature TEWL values and a linear negative relation between the respective temperature capacitance values in the various groups. Furthermore the slope of the temperature-TEWL relations was identical in all groups. Therefore, differences in TEWL levels (comparison at the same temperature) between the respective groups and controls and between the various groups might indicate damage to the skin barrier caused by contact with different irritants and chemicals. However, differences in environment-related variables in the various occupations might also affect TEWL levels. This field study demonstrates, from a practical point of view, how the skin temperature affects TEWL in the various occupations and, as a new point, how sensitive capacitance is to changes in skin temperature. Seasonal variation in TEWL and capacitance was demonstrated among workers in the fish processing industry, with a low TEWL and a high capacitance during summer when the workload is lower. PMID- 1893688 TI - Contact sensitivity to captafol in BALB/c mice. AB - The fungicide captafol has been reported as causing irritant and allergic contact dermatitis in humans and in guinea pigs. This study investigated the ability of purified captafol to cause contact sensitization in BALB/c mice. Female mice were pretreated with an intraperitoneal injection of cyclophosphamide or saline. Applications of captafol (18.7 or 37.4 mg/ml), dinitrofluorobenzene (DNFB; 5 mg/ml) or solvent (4:1 acetone:ethanol mixture) were administered to the shaved abdomen on 2 consecutive days, or on days 1, 2, 8, 15, 22 and 29. Following challenge with captafol (37.4 mg/ml) or DNFB (2 mg/ml) on the right ear 6 days after the last induction, ear thickness ratios (right ear/left ear) were significantly larger after challenge in captafol-induced and DNFB-induced mice compared to control mice. A slightly larger response was observed with the smaller induction dose level of captafol and with multiple inductions over the course of a month. The overall maximum response to captafol was not increased by pretreatment with cyclophosphamide. Histologically, ears from captafol-induced and DNFB-induced mice showed edema and cellular infiltration. This study demonstrated the ability of captafol to produce contact hypersensitivity in the BALB/c mouse. PMID- 1893689 TI - Palladium contact sensitivity. PMID- 1893690 TI - Colorimetric quantification of erythema in the guinea pig maximization test. PMID- 1893691 TI - Relationship between use test and threshold patch test concentration in patients sensitive to 5-chloro-2-methyl-4-isothiazolin-3-one and 2-methyl-4-isothiazolin-3 one (MCI/MI). PMID- 1893692 TI - Bougainvillaea contact urticaria. PMID- 1893693 TI - Allergic contact dermatitis from Capparis spinosa L. applied as wet compresses. PMID- 1893694 TI - The greatest guy in the world. PMID- 1893695 TI - Benefits for the whole office. Staffing practices go upscale. PMID- 1893696 TI - Is part-time teaching for you? PMID- 1893697 TI - Marc Geissberger: student leader. PMID- 1893698 TI - New female intravaginal barrier contraceptive device. Preliminary clinical trial. AB - The Fem Cap, a silicone rubber cervical cap, is shaped like a sailor's hat. While its dome covers the cervix, its rim fits snugly into the vaginal fornices, and its brim adheres and conforms to the vaginal walls. A spermicidal material is applied to the cap, then it is positioned over the cervix by hand or with a special applicator. The device is removed by hand up to 48 hours after insertion, but no sooner than eight hours after intercourse. Women chosen for the trial had contraindications to or were dissatisfied with the currently available contraceptive methods. Each woman was fitted with a cap of suitable size and instructed in its use. She was then asked to note any side effects and the dates of her menses in a diary. One-hundred-twenty-one women were enrolled in the study. Five became pregnant. Of those, two reported dislodgment of the cap during intercourse; the other three admitted to non-use of the cap on several occasions. This device has proven so far to be safe, effective and acceptable to women and men. It has several advantages over the currently available barrier contraceptive devices. The silicone rubber material from which it is made is non-allergenic, durable and easy to clean. Its design fits the anatomy and accommodates physiological changes. The Fem Cap is easy to insert and remove; an applicator facilitates insertion for some women. Instruction for use of the device requires short time from the health care provider. PMID- 1893701 TI - A pilot study on the assessment of a progesterone/estradiol sustained release as once-a-month-injectable contraceptive. AB - A pilot study to assess the use of natural hormones in macrocrystalline sustained release system was undertaken in normal menstruating women. Progesterone at a dose of 100 mg in combination with 5 mg estradiol-17 beta aqueous macrocrystalline suspension (3ml) of defined particle size range (100-250 microns) were administered to five female volunteers of reproductive age, on day 5 of their normal menstrual cycles and then every 28 days consecutively for the next two months. Peripheral venous blood samples were obtained from the women three times a week for 60 days after the third injection for the measurement of serum progesterone, estradiol-17 beta, LH and FSH. The menstrual bleeding patterns were closely monitored during the study period. The results obtained indicate that the exogenous hormone administration produces blood levels similar to those observed during the luteal phase of the menstrual cycle. Follicular maturation as assessed by endogenous estradiol rise, above 150 pg/ml, occurred 29.7 days s.d. 6.4 after the injection. Ovulation as measured by progesterone levels above 5 ng/ml was documented 34.4 days s.d. 4.3 after the third injection. The bleeding patterns were regular though initially shorter but these increased progressively towards normal pattern during course of the study. The data suggest that progesterone/estradiol-17 beta combination administered as an aqueous macrocrystalline suspension is capable of producing sustained ovulation inhibition and could be applied in the design of new once-a-month injectable contraceptives. PMID- 1893699 TI - Evaluation of the effects of a female condom on the female lower genital tract. AB - The purposes of this study were to determine if use of the female condom (Reality) was traumatic to the vaginal mucosa and/or vulvar skin and to determine its effect on resident vaginal bacterial flora. Thirty subjects were randomly assigned to utilize the female condom or diaphragm during the study period. Initially and during 3 follow-up visits, each subject underwent colposcopic examination of the vagina, cervix, and vulva with photographic record, and qualitative fungal, aerobic and anaerobic cultures of the vagina. The two groups were compared with respect to the frequency of abnormal physical findings determined by both macroscopic and colposcopic examination. Visits were compared within each contraceptive group with respect to changes in resident vaginal flora. There was no evidence of significant trauma associated with the use of either contraceptive device during the study period. The resident vaginal flora did not significantly change during the three follow-up visits in patients using the female condom. In diaphragm users, lactobacilli were less frequently isolated at the third (14/15 vs 6/15, P = 0.008) and fourth (14/15 vs 7/15, P = 0.039) follow-up visits when compared to the initial visit. In addition, aerobic gram negative rods were more frequently isolated during the fourth visit (1/15 vs 9/15, P = 0.021) when compared to the first visit. We conclude that neither the female condom (Reality) nor the diaphragm is associated with trauma to the lower genital tract. Subjects using the diaphragm undergo a significant change in vaginal bacterial flora, becoming more likely to be colonized with coliform microorganisms and less likely to maintain lactobacilli colonization. PMID- 1893700 TI - A comparative study of a progestin-only oral contraceptive versus non-hormonal methods in lactating women in Buenos Aires, Argentina. AB - A non-randomized comparative clinical trial of the progestin-only oral contraceptive (POC), Ovrette (75 mcg norgestrel) (Wyeth), versus non-hormonal methods was conducted at two clinics in Buenos Aires, Argentina. The trial was designed to assess the breast-feeding patterns of women choosing progestin-only oral contraception and non-hormonal methods of contraception, and to study the relationship between lactation and the clinical performance of a POC. Five hundred women were allocated to either the progestin-only pill group (n = 250) or to the non-hormonal group (n = 250) and were followed up monthly for six months after admission. Measurements in mean infant weight, mean infant length, and mean head circumference were similar throughout the follow-up period. Non-hormonal users reported significantly more self-perceived decreases in milk production at the 5th and 6th month follow-up intervals. Acceptance and continued use of the pill were excellent, with only one woman discontinuing because of a pregnancy which was attributed to user failure. The principal side effect reported by women in both groups was intermenstrual bleeding. PMID- 1893702 TI - Effect of norethisterone enanthate on endometrial bleeding and changes in coagulation function, ovarian hormones and endometrial histology in Thai women. AB - Endometrial bleeding and alteration in blood coagulation, fibrinolysis, ovarian function and endometrial morphology were studied in twelve normally menstruating women who received the injectable contraceptive norethisterone enanthate (NET-EN) 200mg at 60-day intervals. Levels of clotting factor VII declined significantly during episodes of irregular bleeding compared to those during both normal pretreatment menstruation and the bleeding-free period during treatment. Antithrombin III and fibrinolytic activity, expressed by euglobulin lysis time, showed no marked change. The average level of progesterone during the bleeding free period was slightly but significantly lower than that during the bleeding period. There were no significant alterations in the mean levels of estradiol and the ratio of estradiol to progesterone. The endometrial biopsies showed considerable individual variation and seem to be independent of the effects of NET-EN on ovarian function. PMID- 1893703 TI - Failed contraception in Nigerian women: outcome of pregnancy and subsequent contraceptive choice. AB - The outcome of pregnancy in 56 patients who had contraceptive failure out of the 5,431 new acceptors at the Family Planning Clinic of the Department of Obstetrics and Gynaecology, College of Medicine, University of Lagos, between 1 January 1981 and 31 December 1989, were analysed. There were 40 IUD, 6 OC, and 4 injectable failures. Three patients had had voluntary surgical contraception (VSC) and 3 used barrier methods. The mean +/- SD age and parity were 32.2 +/- 4.4 years and 4.4 +/- 1.9, respectively. There were 17 (30.1%) live births, 34 (56.6%) terminations of pregnancy and 3 (5.2%) spontaneous abortions. Two (3.0%) patients were lost to follow-up. There was neither any statistically significant difference in the outcome of pregnancy between patients with 5 or more children and less than 5 children (p greater than 0.05), nor between patients less than 31 years of age and those older. Fifty per cent of the patients who had used the IUD continued with the method. Seven patients subsequently requested VSC. None of the patients using the injectable contraceptive or barrier methods continued with the method (p greater than 0.05). PMID- 1893704 TI - Effects of mifepristone in vivo on decidual prostaglandin synthesis and metabolism. AB - Mifepristone is an effective abortifacient in combination with an exogenous prostaglandin but its mechanism of action is unknown. Mifepristone stimulates prostaglandin production from decidua in tissue culture. To determine whether this effect also operates in vivo, we treated women with mifepristone 24, 36 and 48 hours prior to surgical termination. Decidua was removed at operation and the ability of the tissue to generate prostaglandin in culture subsequently assessed. Pretreatment with mifepristone 36 hours prior to termination of pregnancy resulted in an increased production of PGF2 alpha in tissue culture (p less than 0.01). A significant decrease in PGFM production was seen 24 hours after pretreatment with mifepristone in vivo (p less than 0.01). These results suggest that the increased uterine activity observed after administration of mifepristone may be due to stimulation of endogenous prostaglandin production and inhibition of prostaglandin metabolism. PMID- 1893705 TI - Prostaglandin-F2 alpha levels in normal saline-induced mid-trimester abortions. AB - In 20 mid-trimester abortion seekers induced by extra-amniotic instillation of normal saline, serial estimation of prostaglandin F2 alpha (PGF2 alpha) in the plasma and extra-ovular space were carried out. It was observed that PGF2 alpha was undetectable in both plasma and the extra-ovular space prior to the onset of induction, and was first detected in the extra-ovular fluid 2 hours after the onset of induction, prior to oxytocin infusion. In the subsequent samples, the prostaglandin concentration in plasma as well as in the extra-ovular fluid was found to rise, with levels in the latter showing a more significant rise with time as compared to the former. Thus, this study confirms the hypothesis that the mechanism of action of extra-ovular normal saline instillation in mid-trimester termination of pregnancy is the result of separation of fetal membranes from the uterine wall, leading to the release of prostaglandins which, in turn, causes uterine contractions leading to abortion. PMID- 1893706 TI - Hirsutism: metabolic effects of two commonly used oral contraceptives and spironolactone. AB - Fifty-one hirsute women were randomly treated for nine months with ethinyl estradiol 35 ug plus norethindrone 0.4 mg or 30 ug ethinyl estradiol plus 1.5 mg norethindrone acetate if they needed contraception or spironolactone 200 mg daily if they did not. Metabolic evaluations in response to therapy demonstrated triglyceride elevations with the two oral contraceptives but not with spironolactone. While systolic blood pressure was lower with spironolactone, fasting insulin levels were higher as opposed to either low-dose oral contraceptive preparation. Ethinyl estradiol 30 ug plus 1.5 mg norethindrone acetate lowered 3-alpha-diol glucuronide levels, yet ethinyl estradiol 35 ug plus norethindrone 0.4 mg and spironolactone were more effective in lowering Ferriman Gallwey Scores. Treatment strategies for hirsute women need to consider metabolic consequences as well as efficacy. PMID- 1893707 TI - An evaluation of the Bioself 110 electronic fertility indicator as a contraceptive aid. AB - The Bioself 110 is a hand-held electronic device that combines the BBT and calendar methods of fertility regulation for planning or preventing pregnancy. A pilot study was undertaken in three centers in the United Kingdom to evaluate the Bioself 110 as a contraceptive aid. This paper deals with 1238 cycles from 131 women. Only one unplanned pregnancy occurred where a volunteer correctly used the Bioself 110 and had intercourse on a supposedly "safe" day. A second pregnancy was experienced by a volunteer who incorrectly used the device and had intercourse on what she though was a "safe" day. Another 11 unplanned pregnancies occurred due to barrier method failures, as well as 11 pregnancies where the volunteers knowingly had unprotected intercourse during the fertile phase. There were five planned pregnancies. The Bioself 110 was correctly used in 71% of the cycles studied. Eighty-four percent of the volunteers indicated that they were satisfied with the Bioself 110 after six to twelve cycles of use. It was concluded that the Bioself 110 can serve as an effective family planning aid and should be added to the menu of contraceptive methods available to women today. PMID- 1893708 TI - A comparative clinical trial of the TCu 380A, Lippes Loop D and Multiload Cu 375 IUDs in Indonesia. AB - The Copper T 380A (TCu 380A), Lippes Loop D (LLD) and the Multiload Cu 375 (MLCu 375) IUDs were evaluated for safety and efficacy in a multicenter randomized clinical trial in Indonesia. A total of 2992 women were enrolled into the study and data for 2845 women were analyzed (147 cases did not meet protocol criteria). Although study IUDs were randomly assigned, LLD users in this study were older and of higher parity than TCu 380A and MLCu 375 users. The 24-month gross cumulative life-table pregnancy rates for TCu 380A, LLD and MLCu 375 users were 1.2, 2.2 and 2.7, respectively. The 24-month expulsion rates for TCu 380A, LLD and MLCu 375 users were 6.7, 7.5 and 5.3, respectively. Overall, 24-month continuation rates were 85.5%, 85.0% and 85.4% for the respective device groups. Differences in both gross and age- and parity-adjusted life-tables rates for the major outcome variables were not statistically significant at 24 months postinsertion. The study suggests that the TCu 380A, LLD and MLCu 375 IUDs seem to be safe and effective contraceptive options for Indonesian women. PMID- 1893709 TI - Oral contraceptives in the etiology of isolated hypospadias. AB - With the objective of identifying whether hypospadias in infants is associated with maternal use of oral contraceptives before pregnancy or in early pregnancy, 846 case-control pairs were collected from eight different malformation monitoring programs around the world and mothers were interviewed using structured questionnaires administered after the birth of the infants. There was no difference in the preconceptional use of oral contraceptives between cases and controls, neither with respect to the number of years of oral contraceptive usage nor the time between stopping oral contraceptives and the present pregnancy. To this material was added data on oral contraceptive usage in early pregnancy from two other sources: an ongoing case-control study in Spain (725 infants with hypospadias) and a population-based study in Sweden (631 infants with hypospadias). There was no statistically significant difference in oral contraceptive exposure in early pregnancy between cases and controls. There is no demonstrable association between oral contraceptive use and infant hypospadias. PMID- 1893710 TI - Acceptability of the vaginal sheath (Femshield) in Thai couples. AB - A small survey to assess the perception and experience of current family planning users and their husbands was carried out in a university family planning clinic. Women routinely visiting the clinic were asked to complete a short Screening Form. Fifty-six women responded to the questionnaire concerning their attitude to the Femshield. Eighteen volunteers agreed to enter the study and were given verbal instruction on use of the device. Each volunteer was provided with 3-5 Femshields. Participants were asked to return to the clinic one month after admission. A Husband Form was then sent to the home of the volunteers to assess the attitude of their husbands. Thirteen volunteers returned for the follow-up visit. Fifty Femshields were used. The results showed that the volunteers found the vaginal insertion of the device was acceptable, but the outer and inner rings of the device caused an uncomfortable feeling when having intercourse. The volunteers were more positive to the device than their spouses. The sexual satisfaction of both partners was reduced. A few couples suggested that the device be modified with the bag being smaller and thinner, the outer and inner rings reduced in size and softer, and the device itself being in a prelubricated packet. PMID- 1893713 TI - CAPD--a decade of experience. Proceedings of the 2nd European Symposium on Peritoneal Dialysis. Alicante, May 25-27, 1989. PMID- 1893711 TI - Physicians' attitudes, recommendations and practice of male and female sterilization in Sao Paulo. AB - While prevalence of vasectomy is low in Brazil, female sterilization is very high. The potential for growth of vasectomy services may be related to attitudes and practices of physicians. In 1984, 660 physicians at seven major hospitals in Sao Paulo were randomly selected from a total population of 2207 physicians in these hospitals. They were interviewed about their attitudes towards family planning in general, and specifically towards voluntary sterilization. A high degree of vasectomy among this medical community is indicated by its relatively high prevalence among married physicians and their spouses; about one in ten reported that either they or their spouse had had a vasectomy. Half of the physicians who perform sterilizations perform vasectomies: 22% of obstetricians and gynecologists, 85% of surgeons, and all urologists. In general, physicians would recommend vasectomy and tubal ligation equally often to their clients. Depending on the circumstances, up to 85% of all physicians recommend some sterilization procedure. Recommendation was modified by the type of procedure a physician performed, and by the patient's characteristics. Physician's recommendations of sterilization increased with age and parity of patient and was related to the health conditions and socioeconomic circumstances of the couple. PMID- 1893712 TI - Antireproductive effect of a potent LHRH antagonist (Nal-Lys antagonist:antide) during early pregnancy in the rat. AB - Effects of a potent third generation LHRH antagonist [Nal-Lys antagonist:antide] have been observed during the first half of pregnancy in rats. A daily dose of 40 micrograms or above, when administered from day 8 of pregnancy, suppressed serum progesterone levels within 48 h and by day 12 there was complete absence of live fetuses. Lower doses of antide (10-20 micrograms) reduced progesterone levels in circulation but were unable to induce abortion consistently in all treated rats. Administration of 150 or 300 micrograms of antide once on day 8 suppressed the progesterone levels within 24 h. Only a dose of 300 micrograms was effective in completely interfering with gestation by day 12 with no observable live fetuses. PMID- 1893714 TI - CAPD in Europe. PMID- 1893715 TI - Intraperitoneal cefazolin and gentamicin in the management of CAPD-related peritonitis. PMID- 1893716 TI - Status of peritoneal dialysis in Latin America. PMID- 1893717 TI - Osmotic agents. An update. PMID- 1893718 TI - Galactose-containing CAPD solutions: kinetics and long-term effects in rats. PMID- 1893720 TI - Alternate use of amino acid and glucose solutions in CAPD. A review. PMID- 1893719 TI - High osmolar amino acid solution: an alternative to glucose? PMID- 1893721 TI - Sodium modelling in CAPD. PMID- 1893722 TI - Outcome and follow-up on CAPD. PMID- 1893723 TI - Peritoneal transport of macromolecules in patients on CAPD. PMID- 1893724 TI - Calcium metabolism in patients on CAPD and hemodialysis. PMID- 1893725 TI - Subcutaneous recombinant human erythropoietin treatment of children undergoing peritoneal dialysis. PMID- 1893726 TI - Low calcium dialysate increases the tolerance to vitamin D in peritoneal dialysis. PMID- 1893727 TI - Peritoneal resting and heparinization as an effective treatment for ultrafiltration failure in patients on CAPD. PMID- 1893728 TI - Arterial calcification in diabetic patients undergoing CAPD. PMID- 1893729 TI - Patient selection and dialysis prescription in peritoneal dialysis. PMID- 1893730 TI - Choice of treatment modality for the infant, child and adolescent with end-stage renal disease. PMID- 1893731 TI - CAPD and systemic diseases. PMID- 1893732 TI - CAPD in children with special aspects of renal transplantation. PMID- 1893733 TI - Hemodialysis and CAPD in diabetic patients. PMID- 1893734 TI - CAPD with three bag exchanges and one day rest. Results of a new protocol. PMID- 1893735 TI - Quality of life of patients with end-stage renal failure. A comparison of hemodialysis, CAPD, and transplantation. PMID- 1893736 TI - Analysis and comparison of treatment costs in peritoneal dialysis and hemodialysis. PMID- 1893737 TI - The straight Tenckhoff catheter. PMID- 1893738 TI - Need for vascular access in CAPD patients in Brazil. PMID- 1893740 TI - The Oreopoulos-Zellermann catheter. PMID- 1893739 TI - Experimental CAPD: a rat model. PMID- 1893741 TI - Peritonitis prevention by eliminating the risk factor disconnection. PMID- 1893742 TI - Heat sterilization of safe.lock connectors using Thermoclav in experimental conditions. PMID- 1893743 TI - CAPD in North America. PMID- 1893744 TI - Reduction of the incidence of peritonitis in CAPD: effectiveness of heat sterilization of Safe. Lock connectors. PMID- 1893746 TI - Assist devices used in the prevention of peritonitis in the USA. PMID- 1893745 TI - Influence of the preservative sorbic acid on human and bacterial cells. PMID- 1893747 TI - Tuberculous peritonitis in patients on CAPD. PMID- 1893748 TI - Changing antimicrobial resistance in CAPD peritonitis? PMID- 1893749 TI - Pharmacokinetic considerations for treatment of bacterial peritonitis during continuous ambulatory peritoneal dialysis. PMID- 1893750 TI - Primary screening and inhibition of macromolecular biosynthesis in Ehrlich ascites cells by benzo(C)fluorene derivatives. AB - The main objective of the present investigation was to screen a series of new benzo(c)fluorene compounds for in vitro activity. It can be stated that each of the 9 newly synthesized benzo(c)fluorene derivatives was about 10 times as active as tilorone. To elucidate the biochemical mode of action, the effects of 2 new compounds (13468 and 14200) on biosynthesis of macromolecules indicated by the incorporation rate of [14C]adenine (DNA, RNA), [14C]-thymidine (DNA), [14C]uridine (RNA) and [14C]valine (protein) were studied in concentration and time dependence. Both compounds inhibited the incorporation of the 4 precursors into the TCA-insoluble fraction of Ehrlich ascites carcinoma cells. PMID- 1893751 TI - Comparison of the effects of piperine administered intragastrically and intraperitoneally on the liver and liver mixed-function oxidases in rats. AB - Piperine, a major pungent constituent of black and red peppers, was administered to rats intragastrically and intraperitoneally to study whether it alters the activities of hepatic mixed-function oxidases (MFO) and serum enzymes as specific markers of hepatotoxicity. An intragastric dose of 100 mg/kg of piperine to adult, male Sprague-Dawley rats caused an increase in hepatic microsomal cytochrome P-450 and cytochrome b5, NADPH-cytochrome c reductase, benzphetamine N demethylase, aminopyrine N-demethylase and aniline hydroxylase 24 h following treatment. On the other hand, a 10 mg/kg dose given i.p. exhibited no effect on the activities of the aforementioned parameters of the hepatic drug-metabolizing enzyme system. However, when the intragastric and intraperitoneal doses were increased to 800 mg/kg and 100 mg/kg, respectively, the black pepper alkaloid produced a significant decrease in the levels of cytochrome P-450, benzphetamine N-demethylase, aminopyrine N-demethylase and aniline hydroxylase 24 h after treatment. None of the treatments significantly elevated the activities of serum sorbitol dehydrogenase (SDH), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and isocitrate dehydrogenase (ICD), suggesting that piperine is not a hepatotoxic agent. PMID- 1893752 TI - The fate of monochlorobenzanilides in the rat. AB - The fate of the three isomeric benzoic acid-substituted monochlorobenzanilides has been studied in the rat after their oral administration. The excretory profile of all three isomers was similar with over half of the dose being excreted in the 0-24 hour urine and between 83-87% being recovered during the three days following administration. The most prominent route of metabolism was that of 4'-hydroxylation on the unsubstituted aniline moiety followed by glucuronic acid conjugation. PMID- 1893754 TI - Computer systems for three-dimensional diagnostic imaging: an examination of the state of the art. AB - This survey reviews three-dimensional (3D) medical imaging machines and 3D medical imaging operations. The survey is designed to provide a snapshot overview of the present state of computer architectures for 3D medical imaging. The basic volume manipulation, object segmentation, and graphics operations required of a 3D medical imaging machine are described and sample algorithms are presented. The architecture and 3D imaging algorithms employed in 11 machines which render medical images are assessed. The performance of the machines is compared across several dimensions, including image resolution, elapsed time to form an image, imaging algorithms employed in the machine, and the degree of parallelism employed in the architecture. The innovation in each machine, whether architectural or algorithmic, is described in detail. General trends for future developments in this field are delineated and an extensive bibliography is provided. PMID- 1893753 TI - The fate of trimethylamine in the rat. AB - The metabolism and excretion of [14C]-trimethylamine has been investigated in seven strains of rat. Over 75% of the administered radioactivity was excreted via the urine within the first day, with up to 9% in the faeces. At this dose level (15 mg/kg body wt) N-oxidation was the major metabolic pathway encountered (45% excreted dose) whilst demethylation was only of minor importance (3%). The remaining compound was excreted unchanged. No significant differences were observed between the strains studied. PMID- 1893755 TI - Models and analysis of compound nerve action potentials. AB - Upon electrical stimulation of a peripheral nerve, a compound action potential (CAP) can be recorded, a procedure that is widely used to study the functional condition of a nerve. The CAP provides relevant information about such parameters as the number of active myelinated fibers and their propagation velocities. This paper reviews methods of model-based CAP analysis that have emerged during the last decade. First, the basic model formulation for the CAP as resulting from a linear summation of the underlying single fiber action potentials (SFAPs) is discussed. Subsequently, a survey is given of volume conductor model approaches for the prediction of the SFAPs. Attention is then concentrated on the "inverse" problem of extracting relevant nerve parameters from experimentally recorded CAPs. Finally, the applicability of such methods is discussed and a direction for future developments is outlined. PMID- 1893756 TI - Research indicates rgp 160 provides long-term immunologic protection. Chimpanzee resists HIV challenge more than two years after vaccination. PMID- 1893757 TI - The revised JCAHO nursing care standards: areas of emphasis. AB - The 1991 JCAHO nursing care standards represent a fundamental shift in the focus of the survey and accreditation processes from specifying the means to clarifying the ends of nursing services and from prescribing structures and processes to clarifying the intended outcomes of nursing care. As critical care nurses prepare to meet the compliance requirements of these new accreditation standards, it will be helpful to keep in mind that our services are nursing care, nursing management, and nursing education or research, but our purpose is quality nursing care. PMID- 1893758 TI - Upper extremity venous thrombosis and central venous catheters. PMID- 1893759 TI - Use of the rubber dam after open heart surgery. AB - The presence of the rubber dam has specific implications for nursing practice. Advantages and complications of the rubber dam, as well as the implications, are discussed in this article. PMID- 1893760 TI - Pathologic pupillary signs: self-learning module, Part 3. AB - Designed for independent study, this module explores some of the common, but often missed, pupillary abnormalities and eye movement irregularities. Part 3 concludes the module and provides the posttest and answer keys for the posttest and the three review exercises in Part 2. PMID- 1893761 TI - Needs of families of critically ill patients: a literature review. AB - More research is needed to assess and address all areas of concern to family members. Options such as family discussion groups, patient-family or psychiatric liaison nurses, or clinical nurse specialist involvement might be used to improve family care and coping. Family perceptions of important needs warrant further research, and nursing interventions such as orientation-education programs, descriptive visitor pamphlets, nurse-family interaction sessions, and open or flexible visiting policies need additional investigation. It is only through continued assessment, evaluation, and intervention that critical care nurses can achieve total care for the ICU patient and family. PMID- 1893762 TI - Biventricular assist devices. AB - Ventricular assistance and its effect on the human body are described in this article. Nursing care based on the physiology of device influence and prevention of complications is also discussed. PMID- 1893763 TI - Epicardial pacing after cardiac surgery. AB - This article focuses on the use of epicardial wires, the different types of pacing therapy, troubleshooting pacemaker problems, as well as the nursing management of the patient receiving epicardial pacing therapy. PMID- 1893764 TI - Critical care competency-based orientation. Part 1. PMID- 1893765 TI - A pocket guide for critical care drug dosing. PMID- 1893766 TI - Effect of humidity on the deswelling function of the human cornea. AB - The present study determined the effect of the full range of humidities on the deswelling function of the human cornea. The closed-eye deswelling function and the open-eye deswelling responses for five different levels of humidity (0%, 25%, 60%, 85%, and 100%) were assessed for 8 normal, young-adult subjects. Open-eye corneal deswelling for the 8 subjects was unaffected by relative humidities from 0 to 100%. Therefore, osmotically-driven corneal thinning effect of tear evaporation does not significantly contribute to the deswelling function of the human cornea. We conclude, contrary to recent reports, that the endothelial pump is the primary mechanism that maintains normal corneal thickness and provides recovery from stromal edema. PMID- 1893767 TI - The roles of laminin and fibronectin in the development of the lens capsule. AB - This study examines the distribution of laminin and fibronectin in the rat lens capsule during development. Both these extracellular matrix glycoproteins are localised in the interspace between presumptive lens and presumptive retina as well as in their basal laminae. The lens capsule arises from multilayering of the basal lamina of the lens cells. Immunofluorescence localises both laminin and fibronectin in the capsule at 16 days of embryonic development, although reactivity for fibronectin is much weaker than for laminin. In the 19 day embryo only laminin is detected. This indicates that during embryonic development fibronectin becomes a minor component of lens cell ECM and is not accumulated in the developing capsule. The roles of laminin and fibronectin in promoting cell migration during development were analysed in explant cultures. Lens epithelial explants from 16, 17 and 19 day old embryos and neonatal rats were grown on a laminin or fibronectin substratum. Lens cells from all ages of rats migrated on the laminin substratum, whereas lens cells progressively lost the ability to migrate on a fibronectin substratum as the age of the donor increased. This developmental loss of ability to migrate on fibronectin in vitro coincides with the developmental loss of fibronectin from the lens capsule in vivo. Therefore, we propose that whilst both laminin and fibronectin may be important for promoting migration of lens cells on their substratum at early stages of lens morphogenesis, during development laminin takes over as the key molecule that promotes migration on the capsule. PMID- 1893768 TI - Temporal variations in the ionic transport across rabbit retinal pigment epithelium. AB - The potential difference (PD), short circuit current (SCC) and resistance (R) of rabbit retina-retinal pigment epithelium-choroid-sclera preparations were measured in a modified Ussing chamber. The rabbits were kept in 14 hour light/10 hour dark cycle conditions for 14 days: tissues were taken for measurement at 1.5, 6, 13, 20 and 23 hours after the start of the fifteenth light period. Significant variations in PD and SCC were observed 6 hours into the light cycle while the resistance remained constant during the test period. When in a second experiment the fifteenth light period was replaced by darkness, the highest PD and SCC values recorded occurred 12 hours after the time when the light period should have started in the normal light/dark cycle. In a third experiment the fifteenth light period was replaced by darkness and the retina was removed. There were variations in the PD and SCC as in the second experiment but the SCC peak was reduced in amplitude. From these preliminary studies it is suggested that these variations may be circadian in origin and may be related to variations in retinal function. PMID- 1893769 TI - Ocular disease leads to decreased concentrations of epidermal growth factor in the tear fluid. AB - The concentration of epidermal growth factor (EGF) in tear fluid (TF) was recently shown to decrease with increasing tear fluid flow (TFF). The purpose of the present study was to clarify the effects of ocular surface disease on the TF EGF concentrations. Tear fluid samples (n = 243) were collected from diseased eyes by means of blunted glass capillaries. The time of collection was measured for each sample, and the tear fluid flow in the capillaries (TFFc) was calculated. The concentration of human EGF (hEGF) was determined using a time resolved immunofluorometric assay (TR-IFMA). For statistical analysis diagnosis dependent multigrouping was performed and the data of the patient groups were compared to the data for a control group. The control material consisted of 271 TF samples collected from healthy eyes before (n = 59) and after stimulation of reflex tearing (n = 212). It was shown that TF specimens of patients (n = 243) contained significantly (p less than 0.001) less EGF (mean 952 pg/ml) than the TF of healthy control individuals before (n = 59 samples; mean 6589 pg/ml) or after stimulation of reflex tearing (n = 212 samples; mean 2762 pg/ml). The EGF concentration of every patient group was significantly lower than that found in the TF of control individuals both before and during reflex tearing (p less than 0.001). The rate of EGF released with TF during collection did not differ significantly between the various groups of patients or from that released with the TF of normal individuals before induction of reflex tearing.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1893770 TI - Characterization of the major cyanogen bromide fragment of alpha-A crystallin. AB - Alpha crystallin from the bovine lens has been digested with cyanogen bromide, and the major fragment (CB-1) has been purified using reverse phase HPLC. Characterization of this fragment by Edman degradation and antisera to synthetic peptides indicates that it originates from alpha-A crystallin, but lacks the N terminal methionine and the last 35 amino acids from the C-terminus of the molecule. The purified CB-1 fragment binds as well as native alpha crystallin to lens membrane, but is unable to self-assemble into the correct size of high molecular weight oligomeric complexes characteristic of the intact alpha-A chain. Together, these results demonstrate that the alpha-A chain is comprised of at least two functional domains, one of which is involved in binding of alpha-A crystallin to lens membrane, and another which is necessary for correct self assembly of the molecule into high molecular weight oligomers. PMID- 1893771 TI - Topical fluoroquinolones: antimicrobial activity and in vitro corneal epithelial toxicity. AB - To assess the potential of fluoroquinolones as topical antimicrobial agents, we evaluated in vitro the antimicrobial activity of five fluoroquinolones (ciprofloxacin, norfloxacin, ofloxacin, pefloxacin, and temafloxacin), as well as gentamicin, tobramycin, and cefazolin against 96 isolates of common bacterial corneal pathogens. Ciprofloxacin and temafloxacin were the most active quinolones [minimal inhibitory concentration inhibiting 90% of stains (MIC90) of 1 microgram/ml], followed by ofloxacin (MIC90 2 micrograms/ml), and norfloxacin and pefloxacin (MIC90s 4 micrograms/ml). In contrast, gentamicin and tobramycin MIC90s were 32 and 64 micrograms/ml, respectively; cefazolin MIC90 was greater than 2048 micrograms/ml. The corneal epithelial cytotoxicity of the fluoroquinolones also was evaluated utilizing an in vitro assay of 3H-thymidine uptake of rabbit corneal epithelial cell cultures. The least to greatest toxicity of the fluoroquinolones were as follows: ciprofloxacin and temafloxacin less than norfloxacin less than ofloxacin less than pefloxacin. Our study suggests that the fluoroquinolones, especially ciprofloxacin and temafloxacin, possess excellent in vitro activity against common bacterial corneal pathogens and are less toxic to the corneal epithelium than the aminoglycosides. PMID- 1893772 TI - Short acting soft mydriatics. AB - Three soft drug analogs of atropine have been tested for mydriatic activity in rabbits' eyes and their in vitro metabolic pathway has been investigated in rat, rabbit and human blood. The three soft drugs were found to produce an equieffective mydriatic activity to atropine and tropicamide. At equieffective concentrations, their durations were shorter with AUC's 12-21% that of 0.25% atropine and 44-80% that of 0.2% tropicamide. The untreated control eyes were observed to dilate after unilateral ocular administration of atropine, but not with unilateral soft drug treatment. In vitro stability studies showed that the soft ethyl analog was less stable in rat blood and rat liver homogenate than in rabbit or human blood. The metabolic product of the soft ethyl derivative in biological media was proven to be the corresponding inactive acidic metabolite predicted by the soft drug design. The ultrashort durations and the potentially nontoxic systemic properties of the soft mydriatics offer promise for use in ophthalmoscopy and in other ocular procedures where a short acting anticholinergic type of mydriatic would be indicated. PMID- 1893773 TI - Liver structure, function, and anatomy: effects of hepatitis B virus. PMID- 1893774 TI - Cellular and molecular mechanisms of hepatocarcinogenesis associated with hepadnavirus infection. PMID- 1893775 TI - Human hepatitis delta virus. PMID- 1893776 TI - Development of antiviral therapy for chronic infection with hepatitis B virus. PMID- 1893777 TI - Inherited hepatic enzyme defects as candidates for liver-directed gene therapy. PMID- 1893778 TI - Viral DNA synthesis. PMID- 1893779 TI - Assembly of hepadnaviral virions and subviral particles. PMID- 1893780 TI - Analysis of hepadnavirus gene expression, biology, and pathogenesis in the transgenic mouse. PMID- 1893782 TI - The nonsurgical treatment of fractures of the dens epistrophei. AB - The authors examined 25 fractures of the dens epistrophei treated conservatively by several methods in order to evaluate the most suitable treatment for this lesion. A Minerva plaster cast proved to be effective in the treatment of type III fractures, while the halo plaster system obtained the best results in type II fractures. PMID- 1893781 TI - Neoadjuvant chemotherapy for the treatment of osteosarcoma of the limbs. Preliminary results in 100 patients treated preoperatively with high doses of methotrexate i.v. followed by cisplatin (i.a.) and adriamycin. AB - One-hundred patients affected with non-metastatic osteosarcoma of the limbs were treated according to a new adjuvant chemotherapy protocol. Preoperative treatment consisted in high doses of methotrexate (i.v.), followed after one week by cisplatin continuous intra-arterial infusion for 72 hours and adriamycin in intravenous infusion for 8 hours. There was good clinical and radiographic response in all of the cases, and conservative treatment was used in 86 cases (86%). A postsurgery histological examination of the segment showed "good" necrosis (greater than 90%) in 75 patients (75%). The incidence of "good" necroses obtained with this protocol was significantly higher as compared to that observed previously at our Center when a preoperative chemotherapy scheme was used, which involved methotrexate and cisplatin alone. Up until now, patients with a good histological response to preoperative chemotherapy have always had an excellent prognosis. Thus, it is our belief that the 23% increase in good histological responses observed must correspond to an increase in the percentage of healing. The preliminary results (83% of patients with no signs of disease) seem to encourage our hypothesis. PMID- 1893783 TI - Medullary compression secondary to acute post-traumatic cervical disc herniation: 5 cases. AB - Based on their observation of 5 cases of acute posttraumatic cervical disc herniation with medullary lesion, as well as on what is reported in the literature, the authors examine the clinical features of the disease, at the same time evaluating and comparing the major diagnostic studies. What emerges from the study is the importance of NMR and CAT in the diagnosis of the lesion. Finally, the authors emphasize the importance of early surgical treatment. PMID- 1893784 TI - Grosse Kempf locked intramedullary nailing in the treatment of diaphyseal fractures of the lower limb. A case review. AB - After a review of the cases (57 between 1981 and 1988) the authors present the results of treatment of diaphyseal fractures of the lower limb by Grosse Kempf locked intramedullary nailing. The advantages and the effectiveness of the method are emphasized; the method has obtained brilliant results in complex and "boundary" fractures of the femur and tibia; furthermore, some suggestions are made with regard to surgery. PMID- 1893786 TI - Bone tumors of the foot: epidemiology and diagnosis. AB - The authors reviewed 260 cases of bone tumors localized in the foot and treated at the Tumor Center of the Rizzoli Orthopaedic Institute: 191 were benign and 58 malignant and 11 metastasis. There was predilection for the hindfoot (57%), followed by the forefoot (33%) (prevalently the metatarsals). Localizations in the midfoot were rare (10%). Osteoid osteoma was observed in 26% of all of the tumors of the foot and in 35% of the benign forms. Among malignant neoplasms Ewing's sarcoma (27.5%) was the most frequent. Conservative surgery, which was always carried out in benign tumors, was also performed in some of the malignant ones, having an early diagnosis and a correct preoperative study. The indications and the limits of the different imaging techniques available are reported (bone scan, arteriography, CAT, MRI), and the role of biopsy in the definitive diagnosis of these neoplasms in discussed. PMID- 1893785 TI - Fractures in myopathies. AB - The paper reports the results obtained in a study on the frequency of fractures in patients affected with Duchenne Muscular Dystrophy and Spinal Muscular Atrophy, types II and type III; the patients were observed between 1974 and 1988 at the muscle clinic of the Rizzoli Orthopaedic Institute. Out of a total of 238 cases, 36 (15.1%) reported one or more fractures during the follow-up period. For each fracture, age, functional capacity, the particular circumstances in which fractures occurred, site and type of fracture, medical treatment and consequences were all considered. A protocol for fracture prevention in neuromuscular patients is proposed, and suitable methods of treatment suggested. PMID- 1893787 TI - Bone scan in the evaluation of cementless hip prostheses. AB - The authors report the data obtained in a bone scan study conducted in 15 patients with cementless total hip arthroplasty. The study was conducted a minimum of 6 months and a maximum of 46 months postsurgery. Contrary to what occurs for cemented prostheses, we used bone scan not as a diagnostic aid for complications, but in order to evaluate the osteogenetic response of the bone to a cementless prosthetic implant. Zonal bone scan high uptake revealed specific areas of overloading, or, when localized in the para-articular region, they anticipated the presence of ossifications before they became visible radiographically. Bone scan was also useful in monitoring the incorporation and remodelling phases of the auto and/or homoplastic bone grafts used. PMID- 1893788 TI - The Leclercq test in diagnosis of tear in the rotator cuff. AB - The authors report their experience in using the Leclercq test to diagnose tear in the rotator cuff of the shoulder. When positive, this test consists in a radiographic demonstration of reduction in the subacromial space in opposing abduction of the shoulder. Twenty-five patients affected with chronic painful shoulder and suspected lesion of the rotator cuff were submitted to the Leclercq test and subsequently to arthrography in order to evaluate the conditions of the cuff. In all of the cases where the cuff was whole, and arthrography normal, the Leclercq test was negative. When lesion of the cuff was revealed by arthrography, the test was positive in 75% of the cases considered globally, and in 92% of the cases with complete tear in the rotator cuff. PMID- 1893789 TI - The biomechanics of pelvic osteotomy according to the Chiari method. AB - The authors analyze the biomechanical effectiveness of pelvic osteotomy according to the Chiari method. This type of operation reduces joint loading and increases the joint support surface. The authors examined 18 patients aged an average of 31 years. This series shows that the effectiveness of pelvic osteotomy according to the Chiari method is particularly observed in cases in which joint morphology is best preserved. PMID- 1893790 TI - Loosening of a hip prosthesis in a patient affected with tabetic disease. AB - The authors present a case of hip Charcot joint treated with cemented arthroplasty. Although there was only weak serological positiveness for lues and no neurological changes associated with the disease, three months after surgery there was dislocation and loosening of the prosthesis. PMID- 1893791 TI - Quiz. Ellis-Van Creveld syndrome or chondroectodermic dysplasia. PMID- 1893792 TI - Engineering and medicine in static of the femur: considerations on the contributions made by Silvio Canevazzi and Cesare Ghillini. PMID- 1893793 TI - CENP-B is a highly conserved mammalian centromere protein with homology to the helix-loop-helix family of proteins. AB - CENP-B is a centromere associated protein originally identified in human cells as an 80 kDa autoantigen recognized by sera from patients with anti-centromere antibodies (ACA). Recent evidence indicates that CENP-B interacts with centromeric heterochromatin in human chromosomes and may bind to a specific subset of human alphoid satellite DNA. CENP-B has not been unambiguously identified in non-primates and could, in principal, be a primate-specific alphoid DNA binding protein. In this work, a human genomic DNA segment containing the CENP-B gene was isolated and subjected to DNA sequence analysis. In vitro expression identified the site for translation initiation of CENP-B, demonstrating that it is encoded by an intronless open reading frame (ORF) in human DNA. A homologous mouse gene was also isolated and characterized. It was found to possess a high degree of homology with the human gene, containing an intronless ORF coding for a 599 residue polypeptide with 96% sequence similarity to human CENP-B. 5' and 3' flanking and untranslated sequences were conserved at a level of 94.6% and 82.7%, respectively, suggesting that the regulatory properties of CENP-B may be conserved as well. CENP-B mRNA was detected in mouse cells and tissues and an immunoreactive nuclear protein identical in size to human CENP-B was detected in mouse 3T3 cells using human ACA. Analysis of the sequence of CENP-B revealed a segment of significant similarity to a DNA binding motif identified for the helix-loop-helix (HLH) family of DNA binding proteins. These data demonstrate that CENP-B is a highly conserved mammalian protein that may be a member of the HLH protein family and suggest that it plays a role in a conserved aspect of centromere structure or function. PMID- 1893794 TI - Two-color hybridization with high complexity chromosome-specific probes and a degenerate alpha satellite probe DNA allows unambiguous discrimination between symmetrical and asymmetrical translocations. AB - This report describes a fluorescence in situ hybridization approach to chromosome staining that facilitates detection of structural aberrations and allows discrimination between dicentric chromosomes and symmetrically translocated chromosomes. In this approach, selected whole chromosomes are stained in one color by hybridization with composite probes whose elements have DNA sequence homology along the length of the target chromosomes. In addition, all chromosomes are counterstained with a DNA specific dye so that structural aberrations between target and non-target chromosomes are clearly visible. Discrimination between dicentric chromosomes and symmetrical translocations is accomplished by hybridization with a second probe that is homologous to DNA sequences found in the centromeric region of all chromosomes. The centromeric marker is visualized in a different color, so that the number of centromeres per aberrant chromosome can be rapidly determined in the microscope by changing excitation and fluorescence filters. PMID- 1893795 TI - Nucleolar organization of HeLa cells as studied by in situ hybridization. AB - The distribution of the ribosomal genes and their ribosomal RNA (rRNA) products in the different compartments of the nucleolus of HeLa cells was examined on thin sections of Lowicryl embedded material. The ribosomal nucleic acids were visualized after hybridization with a set of biotinylated double-stranded ribosomal DNA (rDNA) probes from different locations along the gene, followed by immunogold labelling of biotin. Ribosomal genes were detected over both the entire fibrillar centres (FCs) and some masses of intranucleolar condensed chromatin. As for the rRNA components, comparison of the signal levels obtained with the different probes provides some information about the compartmentalization of distinct stages of ribosome biogenesis. Thus a probe specific for the 5' external transcribed spacer (5'ETS) portion of pre-rRNA labels almost exclusively the dense fibrillar component (DFC) and the border of the FCs, while the interior of the FCs appears devoid of any kind of rRNA species. By contrast, probes recognizing either 18S or 28S mature rRNA sequences label both the DFC and the granular component (GC). Moreover, mature 18S rRNA sequences are markedly under-represented relative to mature 28S rRNA sequences in the GC, as compared with the other nucleolar compartments. Our observations are consistent with the view that DFCs contain elongating and 47S-45S precursor rRNA molecules whereas the subsequent various rRNA processing intermediates are mainly located within the GC. Since the border of FCs is the only site where both rDNA and newly synthesized pre-rRNA coexist, the transcription of ribosomal genes seems to take place at the periphery of the FCs, and not in the DFC, suggesting that elongating and newly completed transcripts are immediately transferred into the surrounding DFC where they transiently accumulate before undergoing processing reactions and transfer to the GC. PMID- 1893796 TI - Scanning electron microscopy of mammalian chromosomes from prophase to telophase. AB - Changes in the morphology of human and murine chromosomes during the different stages of mitosis have been examined by scanning electron microscopy. Two important findings have emerged from this study. The first is that prophase chromosomes do not become split into pairs of chromatids until late prophase or early metaphase. This entails two distinct processes of condensation, the earlier one starting as condensations of chromosomes into chromomeres which then fuse to form a cylindrical body. After this cylindrical body has split in two longitudinally, further condensation occurs by mechanisms that probably include coiling of the chromatids as well as other processes. The second finding is that the centromeric heterochromatin does not split in two at the same time as the rest of the chromosome, but remains undivided until anaphase. It is proposed that the function of centromeric heterochromatin is to hold the chromatids together until anaphase, when they are separated by the concerted action of topoisomerase II acting on numerous similar sites provided by the repetitive nature of the satellite DNA in the heterochromatin. A lower limit to the size of blocks of centromeric heterochromatin is placed by the need for adequate mechanical strength to hold the chromatids together, and a higher limit by the necessity for rapid splitting of the heterochromatin at anaphase. Beyond these limits malsegregation will occur, leading to aneuploidy. Because the centromere remains undivided until anaphase, it cannot undergo the later stage of condensation found in the chromosome arms after separation into chromatids, and therefore the centromere remains as a constriction. PMID- 1893798 TI - Epidemiology of canine babesiosis in relation to the activity of Dermacentor reticulatus in southern Jura (France). AB - Dates of onset of canine babesiosis within a hyperendemic focus in France (Rhone Valley, south of Jura and north of the Alps) were compared to the seasonal population level of the adult stage of Dermacentor reticulatus over a 12-month period (December 1982-November 1983). Cases of babesiosis occurred in spring and fall when adult D. reticulatus were active. The fluctuations of the vector tick population and the onsets of canine babesiosis were also correlated with climatic changes: no tick activity or clinical cases of disease were detected in winter (low temperature) or in summer. The slight disparities observed between both distributions might be explained by various factors such as the development of immunity against the parasites, the intervals between tick bites and appearance of symptoms of the disease, or the asynchrony between different biotopes. PMID- 1893797 TI - A review of the biology and allergenicity of the house-dust mite Euroglyphus maynei (Acari: Pyroglyphidae) [corrected]. AB - Euroglyphus maynei is a commonly occurring mite species in house dust throughout the world, but studies of its biology and allergenicity have been relatively scarce because it is difficult to culture, and because species of the genus Dermatophagoides have attracted most attention of research workers. Euroglyphus maynei has been increasingly recognized as an important source of mite-derived allergens to which patients with house-dust mite allergy are exposed. There is a need for knowledge of its biology and allergenicity, in order to be able to grow it in vitro, and to establish whether or not it produces any unique allergens which do not cross-react with those of Dermatophagoides spp. and which may be of clinical significance. This article reviews published and unpublished data on taxonomy and identification, geographical and habitat distribution, seasonal population fluctuations, life-history and the effects of temperature and humidity, culture techniques and allergenicity of E. maynei. PMID- 1893799 TI - Specificity and effects of host resistance on the African tick Rhipicephalus zambeziensis (Acarina: Ixodidae). AB - Repeated infestations of the rabbit with adult Rhipicephalus zambeziensis ticks resulted in a ten-fold reduction in engorgement weight of adult ticks and a significant decline in engorgement weight of nymphs. There was no evidence of cross-resistance against the South African bont tick, Amblyomma hebraeum. Immunization of rabbits with crude extracts of whole-tick protein significantly influenced engorgement weights and oviposition rates of adult R. zambeziensis. Histological studies of tissues from R. zambeziensis adults fed on resistant rabbits showed severe gut damage; this was associated with the binding of host IgG to mid-gut cells. PMID- 1893800 TI - Pheromone/acaricide mixtures in the control of the tick Amblyomma hebraeum: effects of acaricides on attraction and attachment. AB - Unfed adults and nymphs of the bont tick Amblyomma hebraeum Koch are attracted to hosts on which fed males, emitting an aggregation-attachment pheromone (AAP), are attached. Pheromone/acaricide mixtures have the potential to selectively attract and kill these ticks. We have investigated the effects of three acaricides, amitraz (an amidine), flumethrin (a synthetic pyrethroid) and chlorfenvinphos (an organophosphate), combined with AAP, on the attraction and attachment of the unfed adults. Attraction, measured in field assays involving AAP and CO2, was not inhibited by any of the acaricides. Attachment was measured over 24 h on the ears of rabbits which had been treated with AAP and mixtures of AAP and the acaricides. None of the acaricides inhibited initial attachment. Flumethrin caused rapid and high mortality in attached and unattached ticks. Chlorfenvinphos caused little mortality in the first 24 h on the ears of the rabbits, but 75% of the exposed ticks died over the next 14 days while held in an incubator. Amitraz caused the ticks to detach after an initial period of attachment; there was little mortality in the detached ticks over the next two weeks and they could later be induced to re-attach to other rabbits. Flumethrin was considered to be the compound of choice for use in pheromone/acaricide mixtures. PMID- 1893801 TI - Morphology and structural organization of Haller's organ during postembryonic development of Argas (Persicargas) walkerae (Ixodoidea: Argasidae). AB - Scanning-electron-microscopic investigations of Haller's organ in larvae, nymphs I, II, III and IV, and male and female adult Argas (Persicargas) walkerae ticks showed that morphology and structural organization change during postembryonic development. Stage-dependent differences existed regarding setal numbers of the anterior pit as well as formation and reticulation of cuticular projections in the capsule cavity. The anterior pit increased in size in the course of postembryonic development. It contained only seven setae in larvae, one conical, setiform and grooved seta each as well as two porose and fine setae. Nymphs I, II, III and IV adult ticks had equal numbers of setae; however, one additional unilaterally serrate and grooved seta each were present. Setal length increased continuously during postembryonic development and attained maximum values in adult ticks. The capsule consisted of roof and cavity and was located distinctly lateral in larvae, slightly lateral in nymphs I and II, and in all other stages directly on the longitudinal axis of tarsus. The capsule roof showed a reticular structure. The slit-like main aperture was located peripherally and arranged transversally to the longitudinal axis of tarsus I in larvae. Nymphs and adult ticks had a central, circular main aperture. Stage-dependent cuticular projections of varying form protruded into the capsule cavity. Larvae had only single, free-standing projections which ramified slightly and communicated with each other. Projections were more heavily reticulated in nymphs I and II. In nymphs III and IV as well as male and female adult ticks, a long centrally situated tube of reticular appearance was seen, which was supported by a large number of radially organized and interlocking pillars and communicated with the capsule roof. In all tick stages there were always four porose setae present, arranged on the capsule floor. PMID- 1893802 TI - Can intrahepatic shunting be measured? PMID- 1893803 TI - Combined evaluation of total and functional liver plasma flows and intrahepatic shunting. AB - A diagnostic protocol was studied, designed to evaluate the main parameters of liver circulation in man. A water solution of D-sorbitol (S) and indocyanine green (ICG) was infused intravenously in six controls and nine cirrhotics. Steady state renal and hepatic S clearances as well as hepatic ICG clearance were calculated. In controls the values (mean +/- SD) of the independent measurements of S and ICG hepatic clearance were 978 +/- 107 and 519 +/- 142 ml/min, respectively, while in cirrhotic patients they were 554 +/- 238 and 231 +/- 90 ml/min. Owing to the kinetic properties of S, its hepatic clearance may be regarded as a measure of functional liver plasma flow (FLPF). The total liver plasma flow (TLPF) values (mean +/- SD), calculated according to Fick's principle, were 1091 +/- 157 ml/min (S method) and 1033 +/- 153 ml/min (ICG method) in controls, and 1251 +/- 554 and 1284 +/- 677 ml/min in cirrhotics. In controls, FLPF was found to be very close to TLPF. In cirrhotic patients the difference between TLPF and FLPF (ranging from 169 to 2093 ml/min when measured by S method) was considered as an approximate estimate of intrahepatic shunting. The procedure is safe and simple and may add a new dimension to the investigation of hepatic circulation. PMID- 1893805 TI - Short-term oral zinc supplementation does not improve chronic hepatic encephalopathy. Results of a double-blind crossover trial. AB - The effect of short-term oral zinc supplementation (zinc sulfate 600 mg/day) on hepatic encephalopathy, was assessed in a double-blind, crossover trial. Fifteen cirrhotic patients with stable, chronic hepatic encephalopathy were randomized to receive either oral zinc or a placebo for 10 days. Following a two-week washout period, these were crossed over to the alternate treatment. Conn's index, which comprises the evaluation of the mental state, asterixis, number connection test, EEG record, and plasma ammonia, was used to score the degree of hepatic encephalopathy, both at the beginning and end of each treatment period. Serum zinc was significantly raised after oral zinc administration and reached the levels observed in cirrhotics without hepatic encephalopathy. Despite this, however, no modification in the parameters included in Conn's index were observed. In conclusion, this study failed to confirm that short-term oral zinc supplementation improves chronic hepatic encephalopathy. PMID- 1893804 TI - Prognostic value of galactose elimination capacity, aminopyrine breath test, and ICG clearance in patients with cirrhosis. Comparison with the Pugh score. AB - Seventy-eight patients with cirrhosis were prospectively followed for up to 20 months, on the average. At entry into the study, galactose elimination capacity, aminopyrine breath test, and ICG clearance were measured. At the end of the study, 27 patients had died. Univariate analysis using the Kaplan-Meier method showed that both quantitative liver function tests (galactose elimination capacity: P less than 0.025; aminopyrine breath test: P less than 0.001; ICG clearance: P less than 0.005) and common clinical and biochemical data (encephalopathy: P less than 0.001; ascites: P less than 0.001; serum bilirubin: P less than 0.005; serum albumin: P less than 0.001; prothrombin index: P less than 0.05) were significant predictors of survival. To investigate whether quantitative liver function tests could contribute to a better definition of the prognosis, once Pugh score had already been taken into account, a multiple regression analysis according to the Cox model was performed. Pugh score and galactose elimination capacity resulted in the only independent prognostic covariates. From them a prognostic index was calculated, and the model was validated in an additional sample of 70 patients investigated according to the same protocol. The contribution GEC gave to the assessment of overall prognosis over that obtained using the Pugh score was slight, as estimated by the statistical parameters of the Cox's model, but was significant as assessed by a ROC curve analysis (P = 0.05). These data show that all quantitative liver function tests were predictors of survival in cirrhosis, and that the galactose elimination capacity added some new prognostic information to those already available using the Child-Turcotte-Pugh classification. PMID- 1893806 TI - Hepatic lesions in alcoholic HBV carriers. AB - Liver biopsies were taken from 54 alcoholic HBV carriers with liver dysfunction to assess whether HBV infection or habitual drinking was the main cause of their illness. In 28 cases, ultrastructural studies were done. Results showed that 50% of the cases predominantly displayed virus-related histological changes, whereas 13% of them mainly had alcohol-related ones. Both pathological changes were evenly distributed in four cases. The remaining 15 cases showed nonspecific or other histological changes. Electron microscopy revealed that HBV core and Dane particles were seen with Mallory bodies in the same hepatocytes. Thus, we postulate that HBV-related changes are more often encountered than alcoholic ones in alcoholic HBV carriers and that HBV replication can occur even in hepatocytes bearing Mallory bodies. PMID- 1893807 TI - Role of bile acids in splanchnic hemodynamic response to chronic portal hypertension. AB - Previous studies from our laboratory suggest that humoral factors, namely glucagon, can account for approximately 30% of the splanchnic vasodilation in rats with prehepatic portal hypertension. A reduced vascular sensitivity to norepinephrine, vasopressin, and angiotensin II may contribute to the splanchnic vasodilation. However, neither glucagon nor an altered vasoconstrictor sensitivity can fully account for the splanchnic vasodilation observed in portal hypertensive subjects. Therefore, the present study was designed to examine the role of bile acids in the splanchnic hyperemia of portal hypertension since (1) serum bile acids are elevated in portal hypertensive subjects and (2) bile acids are potent intestinal vasodilators. Prehepatic portal hypertension was induced in Sprague-Dawley rats by surgical constriction of the portal vein. Ten to 14 days after the induction of portal hypertension, the enterohepatic circulation of control and portal hypertensive rats was surgically interrupted. The animals were placed in Bollman restraint cages and allowed to recover. Eighteen to 24 hr later, the rats were anesthetized with sodium pentobarbital and regional blood flow measured with radiolabeled microspheres. Normal and portal hypertensive animals without bile fistula served as controls. Plasma bile acid levels measured by radioimmunoassay were approximately 3.8 times higher in portal hypertensive animals than in control. Bile duct cannulation effectively depleted both normal and portal hypertensive animals of their circulating bile acid pool and significantly reduced portal venous inflow in portal hypertensive but not in control rats. A role for bile acids as partial mediators of the splanchnic hyperemia of portal hypertension is suggested since bile acid depletion did not completely abolish the gastrointestinal hyperemia. PMID- 1893808 TI - Abnormal perception of visceral pain in response to gastric distension in chronic idiopathic dyspepsia. The irritable stomach syndrome. AB - Sensory and pressure responses to gastric distension were evaluated in 24 consecutive patients suffering from chronic idiopathic dyspepsia and 20 healthy subjects. A latex balloon was placed in the proximal stomach and inflated by increments of 100 ml of air up to a maximal volume of 800 ml. Symptom response and intragastric pressure-volume curve were recorded during the gradual balloon distension. Thirteen of the 24 patients experienced pain at a distension volume less than or equal to 400 ml of air, but only one of the 20 controls (P less than 0.001). Intragastric pressure-volume curves were similar in patients and controls, and in patients with and without abnormal pain threshold, suggesting that a compliance defect was not the cause of the sensory anomaly. Gastric emptying of solids and liquids was measured in 20 of the 24 patients using a dual isotopic technique; psychological status was also evaluated in 18 patients using the Mini-Mult test. The frequency of the sensory anomaly was not different in patients with (7/14) or without (4/6) gastric stasis, but was lower in patients with (5/13) than in those without psychological disturbances (5/5, P less than 0.01). Thus, a primary visceral sensory anomaly, either alone or in conjunction with motility disturbances, can play an important role in chronic idiopathic dyspepsia and must be taken in account for further therapeutic research. PMID- 1893809 TI - Idiopathic gastroparesis in patients with unexplained nausea and vomiting. AB - Nausea and vomiting are symptoms sometimes associated with motor dysfunction. We compared a group of young patients suffering from chronic nausea and/or vomiting and normal upper gastrointestinal x-ray series with a control group. The members of both groups underwent isotopic examinations of their stomachs. The aim of the study was to find a simple method of checking the stomach and proving a motor dysfunction in a group of patients with chronic, inexplicable nausea and vomiting. Patients and controls fasted for at least 6 hr were given 0.5 mCI of [99mTc] diethylene triaminopentaacetic acid orally in 150 cc milk with 50 g cornflakes. A time-activity curve was obtained and radioactivity over the stomach was recorded exponentially. The parameter of the T1/2 emptying time was used. In normal controls T1/2 emptying time ranged from 18 to 26 min. Twenty-five symptomatic patients were examined, three of whom achieved normal values, but 22 patients showed pathologic results ranging from 36 to 184 min. In patients with chronic nausea and/or vomiting an isotopic examination of the stomach may provide a simple and rapid diagnostic method of evaluation. PMID- 1893810 TI - Slow gastric emptying induced by high fat content of meal accelerated by cisapride administered rectally. AB - The evaluation of agents potentially accelerating gastric emptying in gastric stasis syndromes is time-consuming. Since a previous study showed that emptying is slowed after antecedent fat ingestion and intravenous cisapride abolishes this effect, we investigated whether emptying delayed by fat incorporated into a meal is reversed by cisapride and thus could serve as a model for such evaluations. Twelve healthy males received, under double-blind conditions, 30 mg cisapride rectally or placebo, and 3 hr thereafter a semisolid meal of low (9.2 g) or high (37.9 g) fat content. The sequence of combinations placebo/low-fat meal, placebo/high-fat meal, and cisapride/high-fat meal was randomized. Gastric emptying and antral motility were recorded scintigraphically. After placebo/high fat, emptying was significantly slower (P less than 0.05) than after placebo/low fat. After cisapride/high-fat, emptying was significantly faster (P less than 0.01) than after placebo/high-fat and similar to that after placebo/low-fat. Antral motility was little affected. The slow emptying of a high-fat meal thus seems a suitable model for the evaluation of prokinetic drug effects. PMID- 1893811 TI - Mucosal humoral immune response to Helicobacter pylori in patients with duodenitis. AB - The humoral immune response to Helicobacter pylori infection in the duodenum has been investigated by short-term in vitro culture, ELISA, and immunoblotting techniques. H. pylori IgA secretion by duodenal bulb biopsies was significantly increased (P less than 0.001) in patients with duodenitis. The IgA response to H. pylori in patients with duodenitis was restricted to the first part of the duodenum; second part duodenal biopsies secreting significantly (P less than 0.001) less IgA during culture in vitro. H. pylori IgG antibody secretion by cultured biopsies was also significantly increased (P less than 0.01) in patients with duodenitis and those with gastric H. pylori infection but without duodenitis. Immunoblotting of duodenal bulb culture supernatants showed positive recognition by the mucosal IgA response of H. pylori antigens in the region of 120, 90, 61, and 31-26 kDa in patients with duodenitis. Serologically, such patients showed little evidence of IgA H. pylori antibodies by immunoblotting. These results demonstrate that the inflammatory response in the duodenal mucosa of patients with duodenitis represents a specific highly localized humoral response to H. pylori. PMID- 1893812 TI - Effects of verapamil and diltiazem on gastric emptying in normal subjects. AB - It has been suggested that calcium-channel blockers may delay gastric emptying by inhibiting gastric smooth muscle contraction. Most reports in man, however, reveal no significant delay in gastric emptying after using nifedipine; other calcium-channel blockers have not been studied in humans to date. We studied the effects of verapamil and diltiazem on solid-phase gastric emptying in 10 healthy volunteers. Each subject underwent a radionuclide gastric emptying determination (1) without preadministered medication, (2) after verapamil 80 mg orally every 6 hr for 10 doses, and (3) after diltiazem 60 mg by mouth given as one dose. Results revealed no significant difference in gastric emptying rates after pretreatment with verapamil or diltiazem when compared with no premedication (P greater than 0.37). We conclude that verapamil and diltiazem do not significantly delay gastric emptying in normal subjects. These data may be of clinical significance when prescribing calcium-channel blockers to patients with diseases associated with altered gastric emptying. PMID- 1893814 TI - Proceedings of the international meeting on normal and neoplastic growth in hepatology, Bari, Italy, June 1989. PMID- 1893813 TI - Neutrophil chemotaxis in gastric mucosa. A signal-to-response comparison. AB - This prospective study compares levels of neutrophil chemotactic activity (NCA) in gastric juice to the neutrophil count in gastric biopsies. Sixty-three male patients enrolled in the study and had antral biopsies following collection of gastric juice during esophagogastroduodenoscopy. Biopsies were examined for the magnitude of gastritis, tissue PMN count, and presence of Helicobacter pylori. Secretions were assayed for neutrophil chemotactic activity. Results show an increase in NCA and in tissue PMN counts with increasing severity of gastritis. H. pylori-positive patients had higher levels of NCA and PMN than H. pylori negative patients. Wide variability in NCA levels preclude a direct correlation between NCA and PMN counts. PMID- 1893815 TI - Structural and functional aspects of regeneration of human liver. AB - Regeneration of human liver was long suspected to occur. It was proven in animals 100 years ago but could not be demonstrated in man until liver biopsy and modern hepatic tests became available. Structural changes in the regenerating liver mainly concern the arrangement of liver cell plates and the size and appearance of hepatocytic nuclei. A return to normalcy in test results depends on the factors responsible for regeneration since various test results change at different rates. Mass, estimated by imaging procedures, is restored parallel with the return of function. Shape is not restored but the pressure of neighboring organs and structures molds the growing remnant so that it almost resembles the original. Factors regulating regeneration in man are beginning to be recognized as they have been in animals. The hope is that regeneration can be accelerated or that cells can be transplanted to replace those lost. PMID- 1893816 TI - Chronic mitoinhibition during promotion of hepatocarcinogenesis. AB - We have reported previously that orotic acid (OA), a precursor for pyrimidine nucleotide biosynthesis, is able to promote carcinogenic process in both liver and duodenum of rats. The present study investigates the possible role of mitoinhibitory effects of OA as being responsible for its promotional effects. Male Fischer 344 rats were given a semisynthetic basal diet (BD) or a diet containing 1% OA for four weeks coupled with 2/3 partial hepatectomy (PH), and all animals were then continued on BD for an additional four weeks. This protocol is known to exert a promoting effect on the initiated rat liver. Livers were perfused, and the labeling index (LI) of isolated cultured hepatocytes was monitored. Hepatocytes isolated from livers of rats fed a BD or 1% OA exhibited in vitro an LI of 39 +/- 2 and 24 +/- 1%, respectively. The lowered in vitro LI was seen even upon exposure to epidermal growth factor (EGF) (67 +/- 2% in OA treated livers compared to 91 +/- 2% in hepatocytes from control rat liver). A similar four-week exposure to OA coupled with PH decreased hepatic DNA synthesis induced by a choline-deficient diet in vivo by about 50%. These results indicate that OA is able to decrease the response of normal hepatocytes to growth factors and suggest a possible mechanism of chronic differential mitoinhibition as a basis for promotion induced by OA. PMID- 1893817 TI - Hepatic regeneration. Effects of age, sex hormone status, prolactin, and cyclosporine. PMID- 1893819 TI - Hepatocyte transplantation. A potential treatment for liver disease. AB - The purpose of this report is to summarize data collected over the past several years in the field of hepatocyte transplantation. Herein, a novel method of intraperitoneal transplantation of hepatocytes attached to collagen-coated microcarriers (or a totally biodegradable collagen sponge) is described, resulting in correction of specific genetic liver defects in rats and improved survival in rats undergoing 90% partial hepatectomy. Transplanted cells/matrix form well-vascularized aggregates in the peritoneal cavity; transplanted hepatocytes can be identified by light microscopy using immunohistochemical methods. Prolongation of transplanted hepatocyte survival and function was demonstrated by pretreatment of cells with ultraviolet irradiation. The ability of transplanted cells to proliferate was examined using both biochemical and morphologic criteria. Finally, a method of harvesting, cryopreserving, and in vivo functional testing of human hepatocytes is described. PMID- 1893818 TI - Prolactin-provoked alterations of cytosolic, membrane, and nuclear protein kinase C following partial hepatectomy. AB - The adenohypophyseal polypeptide hormone prolactin is a potent liver mitogen, stimulating cell cycle progression, an effect that appears coupled to increasing protein kinase C activity in membrane and nuclear fractions. Here, we examine whether hepatocyte proliferation, stimulated by partial hepatectomy, is associated with altered serum prolactin or protein kinase C activation. Within 5 15 min of liver resection, serum prolactin concentrations elevate significantly. Protein kinase C activity in hepatic cytosol decreases significantly, and membrane and nuclear PKC activity increase by 30 min. Hypophysectomy prior to partial hepatectomy abrogates any effect of liver resection on protein kinase C activation in the hepatic remnant. Based upon these data, it is suggested that the rapid increase in serum prolactin seen after partial hepatectomy may be linked to protein kinase C activation, which in turn stimulates the hepatic proliferative response that is essential for hepatic regeneration. PMID- 1893821 TI - Applying standards to practice: the critical step. PMID- 1893823 TI - Preventing complications in acute pancreatitis. AB - Acute pancreatitis is an auto-digestive process with severe complications that can lead to multisystem failure. The nurse is critical in monitoring and preventing complications in these patients. PMID- 1893822 TI - Pressure controlled inverse ratio ventilation in respiratory failure. AB - Since the earliest use of mechanical ventilation for respiratory insufficiency the search has been on for optimal ventilation attuned to different degrees of pulmonary involvement. Pressure controlled inverse ratio ventilation is a recently described ventilatory modality, in which the conventional inspiratory to expiratory ratio is reversed. This method of ventilation allows for stabilization of pulmonary units and diffusion of gases. PMID- 1893820 TI - Artificial liver. State of the art. AB - If an effective hepatic assist system existed, it could serve as a bridge to transplantation. Most of the patients waiting for liver transplantation have chronic liver insufficiency but are not in hepatic coma. Various hepatic assist systems have been used to salvage patients with acute liver insufficiency. Most attempts have been disappointing. The methods used have included plasma exchange, plasma adsorption, double filtration, cryofiltration, thermofiltration, the combination of plasma exchange and amino acid hemodialysis, and others. For patients with chronic liver disease with moderate liver function impairment and limited to one or only a few areas of metabolic abnormality, a hepatic assist might allow the life of the patient to be maintained temporarily. The application of hepatic assist methods for chronic liver disease patients treated at the Cleveland Clinic has been encouraging. One of the patients who suffered from sclerosing cholangitis has maintained a near-normal life for almost five years by 170 plasma treatments. This is in spite of the fact that, at the onset of treatment, the patient was nearly comatose. Unfortunately, this patient did not wish to receive a liver transplantation. Based upon this experience, the concept of a bridge to transplantation approach to hepatic assist devices appears feasible. In addition, it is speculated that hepatic assistance during the early recovery stage of liver transplantation and during mild episodes of rejection may be useful. PMID- 1893825 TI - Differentiating ethical decisions from clinical standards. AB - Clinical standards recommend treatment for patients with different types of critical illnesses. Yet, clinical judgments alone cannot be the sole basis for treatment decisions. This article describes how to distinguish between judgments based on clinical standards and those based on ethical principles. PMID- 1893824 TI - Thoracic aortic dissection: preventing complications. AB - The patient who is admitted to the intensive care unit (ICU) with an acute thoracic aortic dissection represents a nursing emergency. Through astute nursing actions, most complications can be prevented for those patients who have aortic wall injury due to trauma or medical conditions. PMID- 1893826 TI - Developing an effective nursing research committee. AB - If you want to challenge your critical care nurses to participate in nursing research, develop a nursing research committee. Participation on a research committee fosters nurses' research interests and provides an opportunity for them to learn about the research process from a practical perspective. PMID- 1893827 TI - Outcome criteria for patients with implantable defibrillators. AB - Specific outcome criteria that the implantable cardioverter defibrillator (ICD) patient needs to demonstrate before discharge are the basis for independent and collaborative nursing interventions. The authors describe specific outcome criteria for teaching ICD patients. PMID- 1893828 TI - Inflammatory bowel disease. Part I: Nature and pathogenesis. AB - Once regarded as medical curiosities, ulcerative colitis and Crohn's disease have achieved a remarkable change in status recently and today are among the more compelling of all human illnesses. The cause(s) of inflammatory bowel disease (IBD) are not known. Genetic, environmental, microbial, and immunologic factors are involved, but the precise mechanisms are obscure. The incidence of ulcerative colitis is relatively stable, while Crohn's disease continues to increase in frequency. In 10% to 15% of patients, it is hard to differentiate between ulcerative colitis and Crohn's colitis; however, problems with diagnosis usually resolve with time and repeated examinations. In part I of his two-part monograph on IBD, Dr. Kirsner addresses the nature and pathogenesis of the disease. Increased study of ulcerative colitis and Crohn's disease in recent years has generated new knowledge regarding their etiology. Part I focuses on microbial, immunologic, and genetic mechanisms and the inflammatory processes involved in the disease. In part II, which will be presented in next month's issue of Disease a-Month, Dr. Kirsner deals with the clinical features, course, and management of IBD, based on the author's 55 years of experience with these problems and supplemented by critical examination of the recent (1988-1990) literature. Particular attention is directed to the symptoms and physical findings of ulcerative colitis and Crohn's disease, the laboratory, radiologic, endoscopic, and pathologic features, and the many systemic complications. The IBDs are mimicked by several enterocolonic infections and other conditions, making differential diagnosis necessary. Inflammatory bowel disease in children and the elderly conforms to conventional clinical patterns modified by the health circumstances of the respective age groups. Because the cause of IBD has not been established, current medical therapy is facilitative and supportive rather than curative. The principles of medical treatment are approximately the same for ulcerative colitis and Crohn's disease. Treatment emphasizes a program rather than a drug and also considers the individuality of the therapeutic response. A clearer understanding of dietary and nutritional needs, including hyperalimentation and electrolyte and fluid balance, aids treatment. Antidiarrheal and antispasmodic preparations and sedatives are prescribed for symptom relief. The bowel inflammation is controlled with sulfasalazine or the newer 5-amino salicylic acid (5-ASA) compounds, antibacterial drugs for complications of Crohn's disease and IBD, adrenocortical steroids, and the immunosuppressive compounds 6-mercaptopurine (6-MP), azathioprine, and cyclosporine, as determined in each patient. The surgical procedures available for treatment of ulcerative colitis include total proctocolectomy and ileostomy or ileoanal anastomosis.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1893829 TI - [Human RNA-polymerase-II binding of oligonucleotides identical to the regulator elements of eukaryotic gene promoters]. PMID- 1893831 TI - [Differences in the development of the phenomenon of the adaptive stabilization of the DNA in myocardial nuclei during adaptation to stress and altitude hypoxia: the role of heat shock proteins]. PMID- 1893830 TI - [The isolation of the NH2-terminal disulfide nodes of human fibrinogen and fibrin and of their constituent polypeptide chain fragments]. PMID- 1893832 TI - [Patterns in the formation of 3 types of chromosome sets in the bone marrow of rats at different periods of ontogeny]. PMID- 1893833 TI - [The structure-activity relationship in the dehydrogenation processes of 1-methyl 4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) analogs under the action of MAO]. PMID- 1893834 TI - [Thymic involution in mice induced by excess sugar and saturated fat in the dietary ration]. PMID- 1893835 TI - [Adaptation to periodic hypoxia limits the demand for ethyl alcohol and the withdrawal syndrome in the chronic alcoholic intoxication of animals]. PMID- 1893836 TI - [The dependence of the regulatory action of K+ ions on aldosterone formation in the adrenal cortex on protein synthesis]. PMID- 1893837 TI - [Changes in the plastic properties of the neuron under the action of antibodies to specific glycolipid antigens of the glia]. PMID- 1893838 TI - [The dependence of the motility of the bacterium Escherichia coli on cell age]. PMID- 1893839 TI - [The generalized mechanism of the irreversible inhibition of cholinesterase activity by organophosphorus inhibitors]. PMID- 1893840 TI - [Self-excited oscillations in nucleic acid synthesis in Ehrlich carcinoma cells]. PMID- 1893841 TI - [The optimal structure of the microcirculatory system]. PMID- 1893842 TI - [The effect on the restructuring of the neuronal reaction of microfilament stabilization]. PMID- 1893843 TI - [The effect of ts mutations in the agnostic gene controlling calmodulin functions and learning capacity on the ectopic conjugation of polytene chromosomes in Drosophila]. PMID- 1893844 TI - [A statistical analysis and reconstruction of the topography of the molecular markers on the surface of the neuronal membrane]. PMID- 1893845 TI - [The localization of the proteins forming the outer surface of metaphase chromosomes]. PMID- 1893846 TI - [An increase in the production of bile acids by hepatocytes--one of the possible mechanisms of resistance to the development of hypercholesterolemia in rabbits in response to a long-term dietary cholesterol load]. PMID- 1893847 TI - [Positive and inhibitory conditioned reflexes in experimental actions on the apical dendrites of the pyramidal neurons in the cerebral cortex]. PMID- 1893848 TI - [The count, ultrastructure and ultracytochemistry of the blood neutrophils of persons subjected to low-dose radiation exposure during the elimination of the sequelae of the accident at the Chernobyl Atomic Electric Power Station]. PMID- 1893849 TI - [New data on the mechanism of the regulation of duodenal digestion]. PMID- 1893850 TI - [Prediction of peptide antigenic structures recognized by the major histocompatibility complex]. PMID- 1893851 TI - [The effect of temperature on the 3-dimensional organization of polytene chromosomes in Drosophila mutants with altered calmodulin functions]. PMID- 1893852 TI - [Ascorbyl palmitate--an antimutagen with membrane action]. PMID- 1893853 TI - [Ileocolic invagination in adults. The sonographic characteristics]. AB - An 86-year-old man was admitted to hospital because of transitory cramp-like abdominal pain of 6 days' duration. Immediately preceding admission he had suffered a short episode of vomiting and diarrhoea. There was no history of previous abdominal operation. On examination there were signs of incomplete mechanical ileus. Ultrasonography revealed an abnormal cockade with triple ring phenomenon at the ileocaecal junction and the "duck-beak phenomenon" as signs of enterocolic intussusception. Immediate laparotomy demonstrated a submucous lipoma of the terminal ileus as its cause.--If there is clinical suspicion of intussusception, even in the presence of atypical abdominal symptoms, ultrasonography is the procedure of choice to provide rapid diagnosis. In adults treatment is always surgical. PMID- 1893854 TI - [Recurrent hypoglycemia and lactate acidosis in non-Hodgkin's lymphoma]. AB - Two weeks after partial resection of the small intestine for an intra-abdominal stenosing centroblastic non-Hodgkin lymphoma, a 65-year-old man began to experience recurrent attacks of hypoglycaemia (down to 30 mg/dl) together with lactic acidosis (lactate 5.13 mmol/l), tachycardia and sensations of heat. Very high parenteral glucose input (up to 750 g/day) was necessary to maintain normal blood sugar levels. There was close correlation between the level of glucose consumption and the degree of lactic acidosis. After chemotherapy the abnormalities improved, but recurred as the neoplasm proliferated once more. An endocrine mechanism for the hypoglycaemic attacks was excluded by the low serum concentrations of insulin and of "insulin-like growth factors" I and II and by the fact that the levels of glucagon, glucocorticoids, growth hormone and thyroid hormone were within the normal ranges. There were pleural and peritoneal effusions containing large numbers of tumour cells. Investigated in vitro, the fluids showed a decline in glucose and a rise in lactate concentration. Studies with an artificial pancreas also showed that glucose utilization rate in vivo was increased to four times the normal and that it could be raised still further by insulin stimulation. These findings provide evidence of direct consumption of glucose by the tumour cells in the form of abnormally increased anaerobic glycolysis. PMID- 1893855 TI - [Pleural fibrosis as a side effect of years-long methysergide therapy]. AB - A 58-year-old man was admitted to hospital because of exertional dyspnoea and a cardiac murmur not previously heard. For one year he was known to have left-sided fibrinous pleuritis. For 5 years he had been taking methysergide for cluster headaches. From 1950-1980 he had worked with asbestos-containing insulating material. Erythrocyte sedimentation rate was greatly increased to 117/136 mm and there was an hypochromic anaemia (Hb 10.4 g/dl). The cholestasis enzymes were elevated (gamma-GT 88 U/l; alkaline phosphatase 511 U/l). Computed tomography of the thorax demonstrated left-sided pleural thickening of up to 3 cm. Endocarditis was excluded (sterile blood culture; normal echocardiogram). There was no evidence of an infectious, immunological or malignant cause for the pleural fibrosis. One year after pleurectomy and having discontinued methysergide all biochemical tests were normal. PMID- 1893856 TI - [The diagnosis and therapy of de Quervain's subacute thyroiditis]. PMID- 1893858 TI - [The collection of physician's fees through clearing houses outside the practice. The judgement of the Higher Regional Court of Cologne of August 8, 1990 (27 U 76/90)]. PMID- 1893857 TI - [4-Chloro-o-toluidine-induced bladder cancer]. PMID- 1893859 TI - [Therapy in pseudomyxoma peritonei]. PMID- 1893860 TI - [The serological findings in hepatitis B]. PMID- 1893861 TI - [Convulsive crises and cardiovascular complications following high-dosage parenteral administration of naftidrofuryl]. PMID- 1893862 TI - [The carcinogenic effect of chlordimeform and 4-chloro-o-toluidine]. PMID- 1893863 TI - [Analgesic misuse]. PMID- 1893864 TI - Multiple hematopoietic lineages develop from embryonic stem (ES) cells in culture. AB - When embryonic stem cells are cultured directly in semisolid media (methyl cellulose), they proliferate and differentiate to generate colonies known as embryoid bodies (EBs). These EBs consist of differentiated cells from a number of lineages including those of the hematopoietic system. Following 10 days of culture in the presence of 10% fetal calf serum, more than 40% of all EBs from three different ES cell lines, CCEG2, D3 and SQ1.2S8 contained visible erythropoietic cells (i.e. red with hemoglobin). Beta H1 (z globin) mRNA is detectable in EBs within 5 days of differentiation, whilst beta(maj)-globin RNA appears by day 6. In the presence of erythropoietin (Epo), the frequency of EBs with erythropoietic activity increases to greater than 60%; Epo also prolongs this erythropoietic activity. Interleukin-3 (IL-3) does not significantly increase the frequency of EBs that contain erythroid cells, but increases slightly the number of erythropoietic cells associated with them. In the presence of IL-3, in addition to cells of the erythroid lineage, macrophages, mast cells and in some instances neutrophils are found within differentiating EBs. The development of macrophages is significantly enhanced by the addition of IL-3 alone or in combination with IL-1 and M-CSF or GM-CSF. When well-differentiated EBs are allowed to attach onto tissue-culture plates and grown in the presence of IL-3, a long-term output of cells from the mast cell lineage is observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1893865 TI - In situ localization of storage protein mRNAs in developing meristems of Brassica napus embryos. AB - Probes derived from cDNA clones of napin and cruciferin, the major storage proteins of Brassica napus, and in situ hybridization techniques were used to examine changes in the spatial and temporal distribution of storage protein messages during the course of embryogeny, with a special emphasis on the developing apical meristems. Napin mRNAs begin to accumulate in the cortex of the axis during late heart stage, in the outer faces of the cotyledons during torpedo stage and in the inner faces of the cotyledons during cotyledon stage. Cruciferin mRNAs accumulate in a similar pattern but approximately 5 days later. Cells in the apical regions where root and shoot meristems develop do not accumulate storage protein messages during early stages of embryogeny. In the upper axis, the boundary between these apical cells and immediately adjacent cells that accumulate napin and cruciferin mRNAs is particularly distinct. Our analysis indicates that this boundary is not related to differences in tissue or cell type, but appears instead to be coincident with the site of a particular set of early cell divisions. A major change in the mRNA accumulation patterns occurs halfway through embryogeny, as the embryos enter maturation stage and start drying down. Final maturation of the shoot apical meristem is associated with the development of leaf primordia and the accumulation of napin mRNAs in the meristem, associated leaf primordia and vascular tissue. Cruciferin mRNAs accumulate only in certain zones of the shoot apical meristem and on the flanks of leaf primordia. Neither type of mRNA accumulates in the root apical meristem at any stage. PMID- 1893866 TI - Expression of a novel cadherin (EP-cadherin) in unfertilized eggs and early Xenopus embryos. AB - Two distinct cadherin cDNA clones of Xenopus laevis were isolated from a stage 17 embryo cDNA library. Analysis of the complete deduced amino acid sequences indicated that one of these molecules is closely homologous to chicken and mouse N-cadherin, while the other displays comparable homology to both E- and P cadherins and was thus denoted EP-cadherin. This molecule has an apparent relative molecular mass of 125 x 10(3) (compared to approx. 138 x 10(3) or approx. 140 x 10(3) of E-cadherin and N-cadherins, respectively). Northern and Western blot analyses indicated that N-cadherin is first expressed at the neurula stage while EP-cadherin is the only cadherin detected in unfertilized eggs and cleavage stage embryos. Immunolabeling of Xenopus eggs with antibodies prepared against a fusion protein, containing a segment of EP-cadherin, indicated that the protein is highly enriched at the periphery of the animal hemisphere. EP-cadherin was also found in A6 epithelial cells derived from Xenopus kidneys, and was apparently localized in the intercellular adherens junctions. PMID- 1893867 TI - Branching morphogenesis of mouse salivary epithelium in basement membrane-like substratum separated from mesenchyme by the membrane filter. AB - Branching morphogenesis of mouse salivary gland has been studied with organ culture system. We developed a novel transfilter culture system for analyzing branching morphogenesis of the salivary epithelium. The submandibular salivary epithelium from early 13-day mouse fetus, clotted with Matrigel and separated from the mesenchyme by membrane filter, showed extensive growth and branching morphogenesis, morphological differentiation of lobules and stalks, and a typical cleft shape. The epithelium showed little growth and no branching without Matrigel clot or without the mesenchyme. This branching morphogenesis was induced even when the pore size of the filter was reduced to 0.05 microns. Use of type I collagen gel instead of Matrigel mostly induced incomplete morphogenesis with various histological abnormalities. These results suggest that the salivary epithelium can undergo branching morphogenesis in the absence of the mechanical action of mesenchymal cells although it needs an appropriate extracellular matrix and some mesenchymal factors transmitted through the filter. PMID- 1893868 TI - Expression of v-src induces aberrant development and twinning in chimaeric mice. AB - The role of the proto-oncogene c-src in mouse development has been investigated by studying the consequences of expressing its viral homologue, v-src. Embryonic stem (ES) cell lines with differing levels of v-src tyrosine kinase activity have been used to generate chimaeric mice. Whereas a low level of v-src expression is compatible with embryogenesis, chimaeras derived from ES clones with high levels of v-src activity develop abnormally and die on the 8th-9th day of gestation. These abnormalities are characterized by the formation of twin or multiple embryos within the same Reichert's membrane, and by the arrest of embryonic development at the late egg cylinder stage, accompanied by relative expansion of the visceral yolk sac (VYS) and hyperplasia of the VYS endoderm. These results demonstrate for the first time that deregulated expression of the src protooncogene product can induce developmental abnormalities during early embryogenesis. PMID- 1893869 TI - Identification of a cytoskeletal protein localized in the myoplasm of ascidian eggs: localization is modified during anural development. AB - The myoplasm of ascidian eggs is a localized cytoskeletal domain that is segregated to presumptive larval tail muscle cells during embryonic development. We have identified a cytoskeletal protein recognized by a vertebrate neurofilament monoclonal antibody (NN18) which is concentrated in the myoplasm in eggs and embryos of a variety of ascidian species. The NN18 antigen is localized in the periphery of unfertilized eggs, segregates with the myoplasm after fertilization, and enters the larval tail muscle cells during embryonic development. Western blots of one-dimensional and two-dimensional gels showed that the major component recognized by NN18 antibody is a 58 x 10(3) Mr protein (p58), which exists in at least three different isoforms. The enrichment of p58 in the Triton X-100-insoluble fraction of eggs and its reticular staining pattern in eggs and embryos suggests that it is a cytoskeletal protein. In subsequent experiments, p58 was used as a marker to determine whether changes in the myoplasm occur in eggs of anural ascidian species, i.e. those exhibiting a life cycle lacking tadpole larvae with differentiated muscle cells. Although p58 was localized in the myoplasm in eggs of four urodele ascidian species that develop into swimming tadpole larvae, this protein was distributed uniformly in eggs of three anural ascidian species. The eggs of two of these anural species contained the actin lamina, another component of the myoplasm, whereas the third anural species lacked the actin lamina. There was no detectible localization of p58 after fertilization or segregation into muscle lineage cells during cleavage of anural eggs. NN18 antigen was uniformly distributed in pre-vitellogenic oocytes and then localized in the perinuclear zone during vitellogenesis of urodele and anural ascidians. Subsequently, NN18 antigen was concentrated in the peripheral cytoplasm of post-vitellogenic oocytes and mature eggs of urodele, but not anural, ascidians. It is concluded that the myoplasm of ascidian eggs contains an intermediate filament-like cytoskeletal network which is missing in anural species that have modified or eliminated the tadpole larva. PMID- 1893870 TI - alpha-Actin proteins and gene transcripts are colocalized in embryonic mouse muscle. AB - The alpha-actins are among the earliest muscle-specific mRNAs to appear in developing cardiac and skeletal muscle. To determine if there is coexpression of the alpha-actin proteins at early stages of myogenesis, we have used an alpha actin-specific polyclonal antibody and in situ hybridization with specific cRNA probes to cardiac and skeletal alpha-actin transcripts on serial slides of mouse embryo sections. As soon as we can detect alpha-actin mRNAs in embryonic striated muscle, we also detect the protein suggesting that alpha-actin transcripts are translated very rapidly after transcription during myogenesis. In skeletal muscle, this colocalization of alpha-actin mRNA and protein was observed both in the myotomes of somites and in developing muscles in the limbs. In cardiac muscle, alpha-actin transcripts and proteins are abundantly expressed as soon as a cardiac tube forms. PMID- 1893871 TI - Patterns of Evi-1 expression in embryonic and adult tissues suggest that Evi-1 plays an important regulatory role in mouse development. AB - Evi-1 is a putative protooncogene first identified as a common site of retroviral integration in murine myeloid leukemias. It encodes a 145 x 10(3) Mr nuclear DNA binding protein that contains ten zinc-finger motifs separated into two domains, as well as an acidic domain. These features suggest that Evi-1 encodes a transcriptional regulatory protein. In Drosophila, zinc-finger proteins such as Kruppel are involved in body plan patterning, and exhibit a spatially restricted pattern of expression in the embryo. To determine if Evi-1 may be involved in morphogenetic processes in the mouse embryo, we have performed in situ hybridization and Northern blot analysis on embryonic and adult mouse tissues to delineate the spatial and temporal pattern of Evi-1 expression. Our results show that Evi-1 is expressed at high levels in a few tissues in the embryo and is widely expressed, albeit at generally low levels, in the adult. Regions that exhibit high-level expression in the embryo include: the urinary system and the Mullerian ducts; the bronchial epithelium of the lung; focal areas within the nasal cavities; the endocardial cushions and truncus swellings in the heart; and the developing limbs. Expression in the limb occurs at the highest levels from 9.5 to 12.5 days, is present in both hind and forelimbs, is absent at the apical ectodermal ridge, and does not appear to establish a gradient.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1893872 TI - Single cell analysis of mesoderm formation in the Xenopus embryo. AB - We have examined the developmental specification of individual cells in the Xenopus blastula using a new in vitro culture system. Regional differences are apparent at the mid-blastula stage when animal hemisphere cells form only ectodermal cell types, while many clones from below the pigment boundary contain mesodermal cell types. A number of clones give rise to more than one differentiated cell type indicating that the initial steps of mesoderm induction are potentially reversible. Animal hemisphere cells can be induced to form mesoderm by fibroblast growth factor (FGF). Different cell types predominate at different FGF concentrations and the neighbours in this sequence are also the pairs of cell types most usually associated in mixed clones derived from the marginal zone. We propose that the specification of individual cells depends upon both the concentration of inducing factor and on stochastic intracellular events. PMID- 1893873 TI - Involvement of Bone Morphogenetic Protein-4 (BMP-4) and Vgr-1 in morphogenesis and neurogenesis in the mouse. AB - Bone Morphogenetic Protein-4 (BMP-4) and Vgr-1 are members of the TGF-beta gene family most closely related to the Drosophila Decapentaplegic and Xenopus Vg-1 genes. Members of this gene family have been implicated in diverse processes during embryogenesis including epithelial-mesenchymal interactions. Here, we use in situ hybridization to localize BMP-4 and Vgr-1 transcripts during murine development. BMP-4 mRNA is found in a variety of tissues. In the 8.5 days p.c. embryo, transcripts are localized to the mesoderm posterior to the last somite. Later gestation embryos show expression in developing limbs, the embryonic heart, the facial processes and condensed mesenchymal cells associated with early whisker follicle formation. In the developing central nervous system (CNS), BMP-4 expression is restricted to the floor of the diencephalon associated with pituitary development. In contrast, Vgr-1 transcripts are found along the anteroposterior axis of the CNS, in cells immediately adjacent to the floor plate and in the roof plate extending to the forebrain. Together, the data support the hypothesis that polypeptide growth factors of the TGF-beta superfamily play key roles in the initial stages of neurogenesis and organogenesis during murine development. PMID- 1893874 TI - Primitive erythropoiesis of mouse teratocarcinoma stem cells PCC3/A/1 in serum free medium. AB - Mouse teratocarcinoma stem cells PCC3/A/1 differentiated into various types of cells, such as red cells, when they were grown in serum-free medium containing transferrin and bovine serum albumin on a KCF cell feeder layer. These red cells were stained well with 2,7-diaminofluorene (DAF), and therefore were erythroid cells. They were nucleated and contained embryonic globin chains, immunologically identified with antiembryonic hemoglobin antisera after acid urea Triton X-100 polyacrylamide gel electrophoresis (UT-PAGE). The addition of erythropoietin to the culture medium enhanced the production of both embryonic and adult globin chains. The addition of interleukin-3 also enhanced the production of embryonic globin chains, but not the production of adult globin chains. These results indicated that primitive erythropoiesis of PCC3/A/1 teratocarcinoma cells did not require exogenous addition of any hematopoietic factor such as erythropoietin or interleukin-3. This culture system will be a new model system for investigating the factors regulating the primitive erythropoiesis in yolk sac blood islands. PMID- 1893875 TI - Isolation and characterisation of a testis-expressed developmentally regulated gene from the distal inversion of the mouse t-complex. AB - We differentially screened a pool of mouse testis clones in order to identify genes important in germ cell development. One of the isolated clones was found to be expressed only in the male germ line where it is first detected at around the pachytene spermatocyte stage. This gene maps to a subregion of the t-complex in the distal inversion near, but not within, the tw18 and the th20 deletions. A comparison of the t and wild forms of the gene reveals a high degree of sequence conservation. This gene is associated with a CpG-rich island at its 5' end. It encodes a novel protein with extensive alpha-helical structure indicative of coiled-coil interactions. PMID- 1893876 TI - Spatial and temporal changes in the distribution of proteoglycans during avian neural crest development. AB - In this study, we describe the distribution of various classes of proteoglycans and their potential matrix ligand, hyaluronan, during neural crest development in the trunk region of the chicken embryo. Different types of chondroitin and keratan sulfate proteoglycans were recognized using a panel of monoclonal antibodies produced against specific epitopes on their glycosaminoglycan chains. A heparan sulfate proteoglycan was identified by an antibody against its core protein. The distribution of hyaluronan was mapped using a biotinylated fragment that corresponds to the hyaluronan-binding region of cartilage proteoglycans. Four major patterns of proteoglycan immunoreactivity were observed. (1) Chondroitin-6-sulfate-rich proteoglycans and certain keratin sulfate proteoglycans were absent from regions containing migrating neural crest cells, but were present in interstitial matrices and basement membranes along prospective migratory pathways such as the ventral portion of the sclerotome. Although initially distributed uniformly along the rostrocaudal extent of the sclerotome, these proteoglycans became rearranged to the caudal portion of the sclerotome with progressive migration of neural crest cells through the rostral sclerotome and their aggregation into peripheral ganglia. (2) A subset of chondroitin/keratan sulfate proteoglycans bearing primarily unsulfated chondroitin chains was observed exclusively in regions where neural crest cells were absent or delayed from entering, such as the perinotochordal and subepidermal spaces. (3) A subset of chondroitin/keratan sulfate proteoglycans was restricted to the perinotochordal region and, following gangliogenesis, was arranged in a metameric pattern corresponding to the sites where presumptive vertebral arches form. (4) Certain keratan sulfate proteoglycans and a heparan sulfate proteoglycan were observed in basement membranes and in an interstitial matrix uniformly distributed along the rostrocaudal extent of the sclerotome. After gangliogenesis, the neural crest-derived dorsal root and sympathetic ganglia contained both these proteoglycan types, but were essentially free of other chondroitin/keratan-proteoglycan subsets. Hyaluronan generally colocalized with the first set of proteoglycans, but also was concentrated around migrating neural crest cells and was reduced in neural crest-derived ganglia. These observations demonstrate that proteoglycans have diverse and dynamic distributions during times of neural crest development and chondrogenesis of the presumptive vertebrae. In general, chondroitin/keratan sulfate proteoglycans are abundant in regions where neural crest cells are absent, and their segmental distribution inversely correlates with that of neural crest-derived ganglia. PMID- 1893877 TI - Spatial regulation of the gap gene giant during Drosophila development. AB - We describe the regulated expression of the segmentation gene giant (gt) during early embryogenesis. The gt protein is expressed in two broad gradients in precellular embryos, one in anterior regions and the other in posterior regions. Double immunolocalization studies show that the gt patterns overlap with protein gradients specified by the gap genes hunchback (hb) and knirps (kni). Analysis of all known gap mutants, as well as mutations that disrupt each of the maternal organizing centers, indicate that maternal factors are responsible for initiating gt expression, while gap genes participate in the subsequent refinement of the pattern. The maternal morphogen bicoid (bcd) initiates the anterior gt pattern, while nanos (nos) plays a role in the posterior pattern. Gene dosage studies indicate that different thresholds of the bcd gradient might trigger hb and gt expression, resulting in overlapping but noncoincident patterns of expression. We also present evidence that different concentrations of hb protein are instructive in defining the limits of kni and gt expression within the presumptive abdomen. These results suggest that gt is a bona fide gap gene, which acts with hb, Kruppel and kni to initiate striped patterns of gene expression in the early embryo. PMID- 1893879 TI - 'Unmasking' of stored maternal mRNAs and the activation of protein synthesis at fertilization in sea urchins. AB - The isolation and in vitro assay of maternal mRNPs has led to differing conclusions as to whether maternal mRNAs in sea urchin eggs are in a repressed or 'masked' form. To circumvent the problems involved with in vitro approaches, we have used an in vivo assay to determine if the availability of mRNA and/or components of the translational machinery are limiting protein synthesis in the unfertilized egg. This assay involves the use of a protein synthesis elongation inhibitor to create a situation in the egg in which there is excess translational machinery available to bind mRNA. Eggs were fertilized and the rate of entry into polysomes of individual mRNAs was measured in inhibitor-treated and control embryos using 32P-labeled cDNA probes. The fraction of ribosomes in polysomes and the polysome size were also determined. The results from this in vivo approach provide strong evidence for the coactivation of both mRNAs and components of the translational machinery following fertilization. The average polysome size increases from 7.5 ribosomes per message in 15 min embryos to approximately 10.8 ribosomes in 2 h embryos. This result gives additional support to the idea that translational machinery, as well as mRNA, is activated following fertilization. We also found that individual mRNAs are recruited into polysomes with different kinetics, and that the fraction of an mRNA in polysomes in the unfertilized egg correlates with the rate at which that mRNA is recruited into polysomes following fertilization. PMID- 1893878 TI - Mutually repressive interactions between the gap genes giant and Kruppel define middle body regions of the Drosophila embryo. AB - The gap genes play a key role in establishing pair-rule and homeotic stripes of gene expression in the Drosophila embryo. There is mounting evidence that overlapping gradients of gap gene expression are crucial for this process. Here we present evidence that the segmentation gene giant is a bona fide gap gene that is likely to act in concert with hunchback, Kruppel and knirps to initiate stripes of gene expression. We show that Kruppel and giant are expressed in complementary, non-overlapping sets of cells in the early embryo. These complementary patterns depend on mutually repressive interactions between the two genes. Ectopic expression of giant in early embryos results in the selective repression of Kruppel, and advanced-stage embryos show cuticular defects similar to those observed in Kruppel- mutants. This result and others suggest that the strongest regulatory interactions occur among those gap genes expressed in nonadjacent domains. We propose that the precisely balanced overlapping gradients of gap gene expression depend on these strong regulatory interactions, coupled with weak interactions between neighboring genes. PMID- 1893881 TI - Roadmaps to understanding the ear and hearing. PMID- 1893880 TI - Basic FGF and TGF-beta 1 influence commitment to melanogenesis in neural crest derived cells of avian embryos. AB - In previous studies, we showed that neural crest (NC)-derived cells from embryonic quail dorsal root ganglia (DRG) and peripheral nerve (PN), which do not normally give rise to melanocytes, become committed to melanogenesis following treatment in culture with the phorbol ester drug 12-O-tetradecanoyl phorbol-13 acetate (TPA). These and other observations support the notion that melanocytes and Schwann cells are derived from a common bipotent intermediate in the neural crest lineage--the melanocyte/Schwann cell progenitor. In this study, we test the possibility that peptide growth factors found in the embryonic environment might act similarly to TPA to influence the fates of these cells. DRG and PN explants were cultured in medium supplemented with a variety of growth factors, and then the cultures were examined for the presence of pigment cells. We found that basic fibroblast growth factor (bFGF), but not various other growth factors, induced pigmentation in about 20% of these cultures. When low concentrations of TPA were included in the culture medium, bFGF augmented the TPA-induced pigmentation, significantly increasing the proportion of pigmented cultures. These effects of bFGF were age-dependent, and could be blocked by addition of a bFGF-neutralizing antibody to the culture medium. In contrast to these stimulatory effects of bFGF, transforming growth factor-beta 1 (TGF-beta 1) was found to inhibit the TPA- or bFGF-induced pigmentation of DRG cultures. These data suggest, therefore, that at least some NC-derived cells are responsive to bFGF and TGF-beta 1, and that these growth factors may play an important role in the control of NC cell fate. PMID- 1893882 TI - Hair cell regeneration in the avian cochlea: if it works in birds, why not in man? AB - Hearing loss caused by cochlear hair cell loss is the most common process afflicting the hearing impaired. Recent studies in the avian cochlea following ototoxic drug and noise damage have demonstrated a remarkable capacity for anatomical and functional recovery. Hair cell regeneration has been shown to play a major role in this recovery process. Future studies may one day make hair cell regeneration or transplantation possible in man. PMID- 1893883 TI - Computed tomography contrast enhancement of cervical lymphadenopathy. AB - In a prospective study of 51 cases of lymphadenopathy (44 with cervical metastatic nasopharyngeal carcinoma, NPC) using intravenous contrast and computed tomography (CT), a ring enhancement was observed. A retrospective review of 105 cervical carcinomatous lymph nodes (64 with metastatic NPC) showed a prominent peripheral hypervascular pattern not seen in 48 lymphomas and 60 normal controls. We conclude that in carcinomatous cervical lymphadenopathy, enhancement can be achieved by intravenous contrast and CT; and the peripheral hypervascularity is the anatomical basis for the ring appearances seen radiographically. PMID- 1893884 TI - Recidivism in congenital cholesteatoma surgery. AB - Forty-four cases of congenital cholesteatoma in the pediatric age group have been treated surgically. There have been three residual cholesteatomas, which were localized to the anterior aspect of the malleus and were easily excised. Two cases of postero-superior retraction pockets developed post-operatively, and these were treated by conventional tympanomastoid surgery with excision of the retraction pocket and grafting. All five of the patients with recidivism have experienced no further difficulty. PMID- 1893885 TI - Ectopic tooth in the roof of the maxillary sinus. AB - Eruption of a tooth into a nonoral environs is rare. Ectopic eruption of the tooth into the nasal cavity and chin has been reported before. This is a report of an ectopic third molar tooth in the roof of the maxillary sinus, which has not, to our knowledge, been reported before. PMID- 1893886 TI - Vascular malformation of the sphenoid sinus. AB - Isolated sphenoid sinus lesions are usually inflammatory lesions or mucoceles. We report an unusual case of a thrombosed arteriovenous malformation presenting as a unilateral primary vascular malformation of the sphenoid sinus. To the best of our knowledge, no one has ever reported such an entity in the medical literature. Differential diagnosis of sphenoid sinus lesions and possible etiologies for this case will be detailed. PMID- 1893887 TI - Intracranial complications of transnasal ethmoidectomy. AB - The transnasal approach to the ethmoid and sphenoid sinuses is a well-established technique for treating nasal polyposis and chronic sinusitis. The literature supports the effectiveness and safety of this procedure when performed by experienced surgeons. Although various authors allude to catastrophic complications of intranasal ethmoidectomy, there are few case reports of complications involving significant morbidity or mortality. The potential for serious intracranial trauma is present during ethmoid surgery, especially during an intranasal approach due to limited exposure and difficulty in identifying surgical landmarks, but with renewed interest in this approach utilizing endoscopic instrumentation, the risks may be reduced. PMID- 1893888 TI - Fibromuscular temporalis graft implantation for rhinitis sicca. AB - A surgical technique is described of implanting temporalis fascia and muscle beneath the nasal mucosa to reduce nasal dryness and to attempt to normalize the nasal airflow in selected patients with rhinitis sicca secondary to prior nasal surgery. The surgical technique is described in detail and is illustrated in a case report. PMID- 1893889 TI - Gelfoam injection for vocal cord paralysis prior to radiation therapy. PMID- 1893890 TI - Laryngeal lipoma. AB - We present a rare case of an intrinsic lipoma of the left false vocal cord in a 62-year-old man. The tumor was a manifestation of generalized lipomatosis. Successful endolaryngeal removal was accomplished. PMID- 1893891 TI - Sump catheter drainage of parotid abscess: an alternative to surgery. AB - It is a clinical challenge to distinguish patients with parotid abscesses from those with acute sialadenitis. A case of parotid abscess is presented in which a CT scan with intravenous contrast enhancement localized the abscess cavity and guided its aspiration and drainage with an indwelling catheter. By using this percutaneous technique, the need for early surgical intervention by incision and drainage was eliminated. The dense overlying parotid fascia and position of the deep parotid lobe make differentiating between these two clinical entities difficult. Parotid abscesses are readily apparent on computerized tomographic (CT) scanning evaluation with intravenous contrast enhancement, presenting as discrete fluid-filled areas unlike the amorphous appearance of acute sialadenitis. CT scanning with intravenous contrast enhancement has been the preferred radiographic study of choice for evaluating parotid masses or parapharyngeal masses. The treatment of a patient with acute sialadenitis differs from that of a patient with a parotid abscess. Patients with acute sialadenitis will usually respond to vigorous intravenous (IV) hydration, use of sialagogues and appropriate antibiotic coverage. Following a period of conservative treatment with antibiotics and warm soaks, patients with parotid abscesses will usually undergo an incision and drainage procedure, and later, parotidectomy. A case of parotid abscess is presented in which a CT scan with intravenous contrast enhancement localized the abscess cavity and guided its aspiration and drainage with an indwelling catheter. Percutaneous drainage of parapharyngeal abscesses guided by CT has been previously described by Cole. By using this percutaneous technique, the need for early surgical intervention by incision and drainage was eliminated. PMID- 1893892 TI - Emergency department stabilization of pediatric patients with bacterial meningitis. Current advances. AB - The infant or child who presents to the Emergency Department with bacterial meningitis may have nonspecific vague symptoms with few signs of serious illness. However, the disease is often rapidly progressive and life-threatening, and may be associated with respiratory failure, circulatory failure, increased intracranial pressure, disseminated intravascular coagulation, or convulsions, any of which may lead to a fatal outcome. It is important for the triage technician in an Emergency Department to cautiously inspect each young patient who presents with illness, carefully considering whether the presenting syndrome of symptoms and signs might be consistent with early meningitis. If the young patient is triaged in a nonemergent category, then periodic assessments of the patients waiting to be seen may ensure that, when the infant or child with an obscure presentation develops evidence suggesting this diagnosis, the triage technician will promptly notify the appropriate definitive care providers who assume responsibility for immediate definitive evaluation and stabilization. Changes in delivery of lifesaving care to the life-threatened child are being impacted by current advances in the understanding of the biochemical basis of disease at the cellular and subcellular levels. Endotoxin release into the blood causes increased production of kinins, which results in vasodilatation and increased vascular permeability. Members of the leukotriene family may also enhance vascular permeability as well as produce augmented leukocyte aggregation to vascular endothelium, vasoconstriction, and bronchoconstriction. Endotoxin activates the complement cascade and induces platelets to form reversible aggregates that may be trapped in the pulmonary microcirculation; and endotoxemia activated platelets release serotonin, which may be associated with pulmonary hypertension. Now that we have antibiotics that are effective against organisms whose degradation produces endotoxin, there is interest in lessening the host inflammatory response to endotoxin through use of dexamethasone as an anti inflammatory agent. Clinical trials have revealed that patients who received dexamethasone became afebrile earlier and were less likely to acquire deafness after bacterial meningitis. Because administration of antibiotics is the current specific medical therapy for this life-threatening microbial invasion, it is reasonable to continue to strive to shorten the interval between recognition of disease and specific therapy. However, new studies suggest that consequences of the complex host inflammatory response (at the cellular and subcellular level) to microbial invasion and endotoxin release from bacterial degradation are increasingly important in determining survival or severity of morbidity. Therapeutic intervention with specific antibiotics and steroid anti-inflammatory agents for modulating host responses enhances outcome. PMID- 1893893 TI - Use of the infectious disease laboratory in emergency medicine. AB - Until relatively recent advances in the identification of infectious agents, the emergency physician found only limited usefulness of the infectious disease laboratory. There are some tests that can provide information rapidly enough for the Emergency Department setting and new technologies that hold even greater promise for the future. The tests described in this article are currently available in most moderately sized Emergency Departments. PMID- 1893894 TI - Evaluation of the traveler. An introduction to emporiatrics for the emergency physician. AB - Travel medicine, or emporiatrics, presents an additional challenge to the practicing emergency physician. In this time of increased travel for business and pleasure, travel history should become a routine part of patient evaluation. While the emergency physician may not need to become facile with specific details concerning immunizations and prophylaxis, he or she should have a good working knowledge of these in order to provide the potential traveler with some basic information and to be able to adequately evaluate the returned traveler who becomes ill and seeks care. Air travel allows many travelers to arrive back in the United States before manifesting symptoms and signs of illness acquired abroad. Many of these illnesses are not usually found in the United States. Late diagnosis of certain illnesses, such as falciparum malaria, may increase the morbidity and mortality. As such, travel history should become a routine part of patient evaluation, and the physician should have a good working knowledge of illnesses that may be acquired abroad. PMID- 1893895 TI - Tick-borne diseases. AB - Ticks may transmit a variety of human pathogens and are second in importance only to the mosquito as a vector of human disease. The majority of tick-borne diseases are nonspecific in their initial clinical and laboratory presentation and may be confused with a variety of more common illnesses. A history of tick exposure is frequently not available. Although specific serologic tests exist for confirming the diagnosis of many of these diseases, the time required for confirmation of results makes them of little use in the acute situation. Recognition of the epidemiology of tick-borne pathogens and clinical suspicion are of key importance in making the appropriate diagnosis. Early and specific therapy is a principal factor in reducing the morbidity and mortality associated with these diseases. PMID- 1893896 TI - Cat-scratch disease. AB - Cat-scratch disease is a relatively common disorder that is the result of infection with a recently identified gram-negative bacillus. Although it is overwhelmingly a benign, self-limited illness requiring only supportive care, serious complications can occur and the disease may be life-threatening on occasion. Although randomized clinical trials of antibiotic therapy for CSD do not exist, CSD has demonstrated in vitro susceptibility to several antibiotics, and gentamicin has been reported beneficial in a few patients with systemic manifestations of the illness. Therefore, pending clinical trials, gentamicin may be worthy of consideration in CSD patients with serious manifestations of this illness. CSD is one of the most common causes of adenopathy and should be considered in all patients who present with unilateral or regional lymphadenopathy. PMID- 1893897 TI - Work under extreme conditions. AB - Extreme conditions are defined in terms of deviation from the norm, and the mismatch between capacity and demand. Analysis of ergonomic job description data revealed the predominance, through their frequent occurrence, of extreme conditions. Extreme work environment conditions, such as climate, acceleration, and air pressure, are discussed. Task and error-concepts for workers operating under extreme workload are investigated, with reference to Chernobyl, stress strain concepts for ATC, college examinations and shiphandling. PMID- 1893898 TI - Incidence of work-related disorders and absenteeism as tools in the implementation of work environment improvements: the Sweden Post strategy. AB - In 1989, a comprehensive, five-year work environment project (Postal Work Environment [PWE] 2000) was launched by Sweden Post (SP). Its purpose was to identify the jobs and employees with the most exposed work environments and, in conjunction herewith, to initiate remedial programmes. Standardized interviews with a selection of employees and statistical and epidemiological evaluation of illness absenteeism and occupational injuries served as input data for devising different measures of work-related ill health (subjective complaints, symptoms, illness, illness absenteeism, and occupational injury). The results provided an incentive to regional action programmes, in which 'risk areas and risk occupations' were correlated with the load factors, primarily in ergonomic and work organization areas, cited in interview replies. In its regional efforts. PWE 2000 served as a stimulus/catalyst in the implementation of various regional action programmes. PMID- 1893899 TI - The energy cost of running increases with the distance covered. AB - The net energy cost of running per unit of body mass and distance (Cr, ml O2.kg 1.km-1) was determined on ten amateur runners before and immediately after running 15, 32 or 42 km on an indoor track at a constant speed. The Cr was determined on a treadmill at the same speed and each run was performed twice. The average value of Cr, as determined before the runs, amounted to 174.9 ml O2.kg 1.km-1, SD 13.7. After 15 km, Cr was not significantly different, whereas it had increased significantly after 32 or 42 km, the increase ranging from 0.20 to 0.31 ml O2.kg-1.km-1 per km of distance (D). However, Cr before the runs decreased, albeit at a progressively smaller rate, with the number of trials (N), indicating an habituation effect (H) to treadmill running. The effects of D alone were determined assuming that Cr increased linearly with D, whereas H decreased exponentially with increasing N, i.e. Cr = Cr0 + a D + He-bN. The Cr0, the "true" energy cost of running in nonfatigued subjects accustomed to treadmill running, was assumed to be equal to the average value of Cr before the run for N equal to or greater than 7 (171.1 ml O2.kg-1.km-1, SD 12.7; n = 30).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1893900 TI - Ratings of perceived exertion in chronic obstructive pulmonary disease--a possible indicator for exercise training in patients with this disease. AB - The purpose of this study was to evaluate the usefulness of ratings of perceived exertion (RPE) as an indicator of exercise intensity in patients with chronic obstructive pulmonary disease (COPD). The subjects were ten male patients with COPD, whose mean forced expiratory volume in 1 s was 1.09 1, SD 0.41, and ten healthy middle-aged men. Ramp incremental exercise on a cycle-ergometer was performed and RPE was determined by the Borg 15-point scale. The absolute oxygen uptake at each RPE was significantly greater in the healthy subjects than in the patients with COPD. However, oxygen uptake calculated as a percentage of maximal at any RPE did not differ significantly between the two groups. Arterial blood lactate concentration at points 15 to 19 on the RPE scale was increased in healthy subjects (P less than 0.05-P less than 0.001), while the dyspnoea index at points 11 to 19 on the RPE scale was higher in patients with COPD (P less than 0.05-P less than 0.001). The main complaints on stopping exercise were dyspnoea in the patients with COPD and fatigue in the healthy subjects. Although the nature of RPE may have been different in the two groups, RPE could be a possible indicator of exercise intensity when physicians prescribe exercise to patients with COPD. PMID- 1893901 TI - Peak anaerobic power in master athletes. AB - The age-related decline in maximal physical performance of healthy subjects may be attributed both to the aging process per se and/or to a progressive reduction in physical activity. In two groups of master athletes, power (P) or endurance (E) trained (n = 115; aged 40-78 years), the degree and rate of the age-related deterioration of the maximal instantaneous muscle power (peak power, Wpeak), and the relative contribution of quantitative (muscle mass) and qualitative factors possibly underlying such deterioration were determined. Two groups of young athletes (n = 20; 17-26 years) and healthy untrained subjects (U, n = 37; 22-67 years) were also tested for comparison. The following two variables were assessed, firstly the lower limb muscle plus bone volume (LMV) by anthropometry, and secondly Wpeak, by means of a standardized vertical jump off both feet, performed on a force platform. The results obtained were that LMV of E and P, as well as of U, was about the same between age 20 and 45 years, whereas at older ages a progressive reduction was observed; the LMV values were higher in P than in E and U.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1893902 TI - Training effects of cross-country skiing and running on maximal aerobic cycle performance and on blood lipids. AB - Two experiments were carried out to compare the cardiorespiratory and metabolic effects of cross-country skiing and running training during two successive winters. Forty-year-old men were randomly assigned into skiing (n = 15 in study 1, n = 16 in study 2), running (n = 16 in study 1 and n = 16 in study 2) and control (n = 17 in study 1 and n = 16 in study 2) groups. Three subjects dropped out of the programme. The training lasted 9-10 weeks with 40-min exercise sessions three times each week. The training intensity was controlled at 75%-85% of the maximal oxygen consumption (VO2max) using portable heart rate metres and the mean heart rate was 156-157 beats.min-1 in the training groups. In the pooled data of the two studies the mean increase in the VO2max (in ml.min-1.kg-1) on a cycle ergometer was 17% for the skiing group, 13% for the running group and 2% for the control group. The increase in VO2max was highly significant in the combined exercise group compared to the control group but did not differ significantly between the skiing and running groups. The fasting serum concentrations of lipoproteins and insulin did not change significantly in any of the groups. These results suggested that training by cross-country skiing and running of the same duration and intensity at each session for 9-10 weeks improved equally the cardiorespiratory fitness of untrained middle-aged men. PMID- 1893904 TI - Muscle cross-sectional area, force production and relaxation characteristics in women at different ages. AB - Thirty women, divided among three different age groups, i.e. 30 years (range 26 35; n = 10), 50 years (range 46-55; n = 10) and 70 years (range 66-75; n = 10) volunteered as subjects for examination of the characteristics of the muscle cross-sectional area (CSA), maximal voluntary isometric force, isometric force time and relaxation-time of their leg extensor muscles. The CSA of the quadriceps femoris muscle in the youngest age group was slightly larger (NS) than in the middle-aged group and much larger (P less than 0.01) than in the oldest age group whose CSA was markedly smaller (P less than 0.01) than the middle-aged group. Maximal force in the youngest group was slightly greater (NS) than in the middle aged group and much greater (P less than 0.01) than in the oldest group whose values were markedly smaller (P less than 0.05) than the middle-aged group. The individual values in CSA correlated with maximal force both in the total subject sample (r = 0.82; P less than 0.001) and in the three age groups separately (r = 0.72; P less than 0.01; r = 0.86; P less than 0.01 and r = 0.67; P less than 0.05, respectively). When the force values were related to the CSA of the muscle, the mean values of 45.4 N.cm-2, SD 5.6, 47.6 N.cm-2, SD 5.0 and 46.8 N.cm-2, SD 7.0 for the three groups did not differ significantly from each other.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1893903 TI - Leg skin temperature and thigh sweat output: possible central influence of local thermal inputs. AB - To demonstrate whether or not the skin temperature of one lower limb can have an influence on the sweat rate of the contralateral leg, the two legs of five subjects were exposed inside leg-chambers to specific local thermal conditions while sweat rates were measured on both limbs. Three experiments (C I, II, III) of 3 h were carried out: each included two phases A and B. During A, the right leg was not ventilated, while the left leg was (C I) or was not (C II-III) ventilated. During B, the legs were either removed from the leg-chambers (C I) or ventilated inside the chambers at differently controlled levels of leg skin temperature (C II-III). At all times, sweat capsules on both legs measured the sweat rates of local areas of the thigh which were also temperature-controlled. Results showed that, at constant or slightly increased mean skin and core temperatures, the sweat output of one leg could be decreased at constant (C II) or higher local skin temperature (C III) probably due to a decrease in the temperature of the opposite leg. This finding is interpreted as a consequence of a central negative effect, originating from contralateral thermal inputs. PMID- 1893905 TI - Use of a Kin-Com dynamometer to study the stretch-shortening cycle during plantar flexion. AB - The aim of this study was to evaluate the Kin-Com II dynamometer in the study of the stretch-shortening cycle (a concentric muscle action preceded by an eccentric muscle action). Measurements were made of plantar flexion at different angular velocities (120 degrees.s-1 and 240 degrees.s-1) with the knee at two different angles (0 degree and 90 degrees). Ten healthy women ranging in age from 22 to 41 years were studied. Torque values were recorded simultaneously with surface electromyograms (EMG): maximal voluntary concentric torque values were recorded and, after a short rest, the torque values of the concentric action which followed immediately after an eccentric action of the same velocity, both with maximal effort. Mean values were taken at different ankle positions and also averaged over different ranges. A concentric action preceded by an eccentric action generated a torque value on an average about 100% larger than a concentric action alone. The EMG activity was lower or unchanged. It was concluded that the present method could be useful in the study of the stretch-shortening cycle in plantar flexion and in the testing of the behaviour of the elastic components in people with disabilities in the lower limbs. PMID- 1893906 TI - The effects of caffeine on graded exercise performance in caffeine naive versus habituated subjects. AB - The physiological effects of caffeine on subjects habituated to caffeine is relatively unstudied compared to those of caffeine naive subjects during graded exercise. Thus, the purpose of this investigation was to determine the effects of caffeine on maximal oxygen consumption (VO2max) and the anaerobic threshold in these two populations. Seventeen moderately trained males were classified according to caffeine usage: (1) caffeine consumption 25 mg.day-1 or less (CN) (n = 8) or (2) caffeine consumption above 300 mg.day-1 (CH) (n = 9). The subjects were tested post-absorptive on the same cycle ergometer on three occasions with 7 days separating the tests. One hour before each test the subject ingested either a gelatin capsule (C); 3 mg.kg-1 body weight of caffeine (C3); or 5 mg.kg-1 body weight of caffeine (C5). The subject then performed an incremental VO2max test beginning at 50 W and the work rate was increased 30 W every 2 min until the subject could not maintain the power output. Serial venous blood samples were drawn over 30 s at the end of each stage. The CN group significantly increased resting heart rate (fc) and expired ventilation volume (VE) after C3 and C5 and VO2 after C5. No significant differences were found for exercise VE, VO2, respiratory exchange ratio, fc or time to exhaustion. There were no significant differences (P less than 0.05) in the lactate threshold or the ventilatory threshold between treatment in either group. The CH subjects showed a significant increase (P less than 0.05) in resting plasma free fatty acid (FFA) concentration only during the C3 and C5 treatments.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1893907 TI - Effect of shortening velocity on work output and energy cost during repeated contractions of the rat EDL muscle. AB - The effect of shortening velocity on the reduction in work output, energy consumption and efficiency during repetitive contractions has been determined in rat extensor digitorum longus muscle. Muscles in situ (with occluded blood flow, 37 degrees C) were stimulated to perform 40 successive contractions (at 4 Hz) with a total duration of the exercise period of 10 s and shortening velocities of either 25, 50 or 75 mm.s-1 (whole muscle-tendon complex). Care was taken that work output during the shortening phase of the first contraction was the same for the different velocities used. Total work output of the 40 contractions was not significantly different between the three groups with different shortening velocities; nor was there a significant difference in the high-energy phosphate consumption over this 10-s exercise period. However, when the ratio of total work output and total energy consumption was calculated a significantly higher efficiency (25-30% in comparison with the efficiency of the other two velocities) was found with the shortening velocity of 50 mm.s-1. There was no significant difference in efficiency between shortening velocities of 25 and 75 mm.s-1. This suggests that with this protocol efficiency showed a velocity-dependent pattern that may have the same shape as the power/velocity curve. Whereas total work output during the 10-s exercise period was not significantly different between the velocities studied, the time course of the changes in work output was quite different. With shortening velocities of 50 and 75 mm.s-1 work output initially increased by maximally 6% and 12% respectively in contrast to a steady level in the contractions with a velocity of 25 mm.s-1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1893908 TI - Zero crossing rate of electromyograms during occupational work and endurance tests as predictors for work related myalgia in the shoulder/neck region. AB - The relationship between electromyographic signs of fatigue (ESF) during work and occupation-related myalgia in the shoulder/neck region was investigated in a longitudinal study. Forty-three healthy female assembly workers were studied over 2 years. Measurements were performed at the start of the study with follow-up measurements after 1 and 2 years. The ESF were estimated as the zero crossing rate of electromyograms (EMG) detected during short test contractions performed during short breaks in normal work. As a complement, an endurance test using EMG records was performed and analysed with the zero crossing technique. The occurrence of shoulder/neck disorders was assessed by a clinical investigation and a questionnaire. No significant relationship between ESF during work in year 0 and deterioration of the disorder was seen. On the other hand, the absolute zero crossing rate and the time constant of the zero crossing decline from the endurance test showed a significant relationship with deterioration of the disorder. The ESF during work year 2, showed a significant relationship with disorder year 2, while the endurance test parameters year 2 did not. It was concluded that ESF during work was not a predictor of muscle injury, whereas it could be useful as a diagnostic tool. PMID- 1893909 TI - The combined effect of the cold pressor test and isometric exercise on heart rate and blood pressure. AB - The purpose of this study was to determine if the cold pressor test during isometric knee extension [15% of maximal voluntary contraction (MVC)] could have an additive effect on cardiovascular responses. Systolic and diastolic blood pressures, heart rate and pressure rate product were measured in eight healthy male subjects. The subjects performed the cold pressor tests and isometric leg extensions singly and in combination. The increases of systolic and diastolic blood pressure during isometric exercise were of almost the same magnitude as those during the cold pressor test. The responses of arterial blood pressure, and heart rate to a combination of the cold pressor test and isometric knee extension were greater than for each test separately. It is suggested that this additional effect of cold immersion of one hand during isometric exercise may have been due to vasoconstriction effects in the contralateral unstressed limb. In summary, the circulatory effects of the local application of cold during static exercise at 15% MVC were additive. PMID- 1893911 TI - Bradykinin agonist activity of a novel, potent oxytocin antagonist. AB - From a series of potent cyclic hexapeptide oxytocin (OT) antagonists, a compound that exhibited significant bradykinin (BK) agonist activity was identified. L 366,811 (cyclo[L-proline-D-tryptophan-L-isoleucine-D-pipecolic acid-L-piperazine 2-carboxylic acid-N-Me-D-phenylalanine]) stimulated phosphatidylinositol (PI) turnover in rat uterine slices in vitro (approximately EC50, 2 microM) with a maximal effect (15-fold increase over basal) greater than that obtained for either BK or OT. L-366,811 also elicited dose-related contractions of the isolated rat uterus, producing measurable effects at 100 nM. Several other equally potent OT antagonists from the cyclic hexapeptide structural class were either less potent or inactive as activators of uterine PI turnover or contractility. The stimulatory effects of L-366,811 on uterine PI turnover and contractions were blocked by BK antagonists but not by an arginine vasopressin (AVP)/OT antagonist. In radioligand binding studies, L-366,811 exhibited moderate affinity (IC50, 360 nM) for the [3H]BK binding site in rat uterus, consistent with its potency in the functional models. These results indicate that L-366,811 exhibits BK agonist activity in rat uterus in vitro. PMID- 1893910 TI - Carnitine administration as a tool of modify energy metabolism during exercise. PMID- 1893912 TI - Comparative behavioral and pharmacological studies with centrally administered kynurenine and kynurenic acid in rats. AB - In the present study the effects of kynurenine and its metabolite kynurenic acid were compared in different behavioral and pharmacological tests. Kynurenic acid administered i.c.v. resulted in ataxia and stereotypy in a dose-dependent manner (0.025-1.6 mumol). Administration of 0.8 mumol of kynurenic acid resulted in sleeping and an approximate 25% mortality of the animals. At a dose of 1.6 mumol all of the animals died within 2-5 min from cardiorespiratory failure. One hour after lower doses of kynurenic acid the behavior of the rats appeared normal (neither stereotypy nor ataxia were observed in their familiar environemnt), but their exploratory activity (0.025-0.2 mumol) was significantly lower in a novel environment (open-field box) compared to the control group. Twenty four hours after the injection of kynurenic acid the exploratory activity of the animals did not differ from the control group. Kynurenine administered i.c.v. in equimolar doses did not result in stereotypy, ataxia, sleeping or mortality of the animals although, immediately after high doses short-lasting (1-2 min) immobility was observed. The rearing activity of the high dose kynurenine-treated animals was lower 1 h after injection, but this effect disappeared 24 h after the treatment. Post-trial injection of kynurenic acid (0.2 mumol) slightly, but not significantly, inhibited the learning ability of the rats in an active avoidance paradigm. Kynurenine administered in an equimolar dose had no effect on the speed of learning, but significantly attenuated the intertrial activity of the rats. Kynurenic acid (0.2 mumol, 0.4 mumol) did not significantly inhibit the passive avoidance latency of the animals after post-trial treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1893913 TI - Characterization of muscarinic receptors of bovine coronary artery by functional and radioligand binding studies. AB - The nature of the muscarinic receptor subtype mediating contraction of the endothelium-denuded bovine coronary artery was investigated in vitro by functional measurements and radioligand binding studies. The acetylcholine (ACh) induced isotonic contraction of circularly cut muscle strips was recorded and expressed as a percentage of the maximum contraction obtained with 80 mM K+. In order to distinguish between M1, M2 and M3 receptors, the potency of the five subtype-selective antagonists, 4-diphenylacetoxy-N-methyl-piperidine methobromide (4-DAMP), parafluor-hexahydro-siladifenidol (pFHHSiD), pirenzepine, AF-DX 116 and methoctramine, to block the ACh-induced contraction was estimated. All the antagonists competitively inhibited the responses induced by ACh, with one exception, namely, 4-DAMP, whose Schild plot had a slope greater than one. The low affinity of pirenzepine (pA2 7.14 +/- 0.14) excluded an action at the M1 subtype. The low affinity of AF-DX 116 (pA2 6.49 +/- 0.18) and methoctramine (pA2 5.88 +/- 0.07) suggest that the bovine coronary artery smooth muscle receptor is not of the M2 (cardiac) subtype. In contrast, 4-DAMP (pA2 9.04 +/- 0.03) and pFHHSiD (pA2 7.64 +/- 0.04) potently inhibited the ACh-induced contraction with affinities similar to those reported for the M3 (glandular) receptor. In addition, the muscarinic receptors mediating coronary artery contraction were characterized in antagonist/[3H]N-methyl-scopolamine ([3H]NMS) competition binding studies. With the exception of AF-DX 116, all antagonists bound to a homogeneous population of receptors with pseudo-Hill slopes not different from unity. The pKi values, albeit somewhat lower, essentially substantiated the functional affinity estimates.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1893914 TI - Electrophysiology of the 5-HT1A ligand MDL 73005EF in the rat hippocampal slice. AB - The actions of 5-hydroxytryptamine (5-HT) and the 5-HT1A receptor ligand MDL 73005EF on neuronal activity in the CA1 region of rat hippocampal slices in vitro were recorded using intra- and extracellular recording techniques. 5-HT (1-30 microM) hyperpolarised the pyramidal neurones in a concentration-dependent manner and reduced membrane resistance and action potential after-hyperpolarisations (AHPs). MDL 73005EF (1-30 microM) had no clear effects on membrane potential, membrane resistance or AHPs. However, prior application of 3 microM MDL 73005EF to the slices for 10-60 min antagonised the hyperpolarisation induced by 30 microM 5-HT but not the reduction in spike AHP or the hyperpolarisation induced by the GABAB receptor agonist baclofen. MDL 73005EF and the 5-HT1A/2 receptor antagonist spiperone (both 3 microM) reduced the frequency and amplitude of spontaneous inhibitory (bicuculline-sensitive) postsynaptic potentials. Extracellular recordings of population action potentials revealed that MDL 73005EF did not prevent the induction or maintenance of hippocampal long-term potentiation or exhibit local anaesthetic properties. It is concluded that MDL 73005EF is an antagonist at 5-HT1A receptors on hippocampal CA1 pyramidal neurones. PMID- 1893915 TI - Caffeine-induced contractions in rabbit isolated renal artery are differentially inhibited by calcium antagonists. AB - Caffeine (1-60 mM) induced concentration-dependent, endothelium-independent phasic contractile responses in isolated rabbit renal artery ring preparations. For concentrations of caffeine over 2 mM, responses were mainly the result of intracellular calcium ion mobilization since they were relatively resistant to removal of calcium ions from the bathing medium. The L-type slow calcium channel blocker, nifedipine (10 microM), had no effect and high concentrations of verapamil and diltiazem (10-30 microM) only slight and inconsistent effects (not concentration-dependent) upon these caffeine responses. Likewise, the highly lipophilic calcium antagonists flunarizine and lidoflazine (3-30 microM) only slightly displaced caffeine concentration-response curves to the right and reduced the maximum response. These small inhibitory effects of flunarizine and lidoflazine were not augmented in a calcium-free medium. In contrast, the other lipophilic calcium antagonists, bepridil and fendiline (3-30 microM), produced marked, non-competitive type inhibition of caffeine responses, completely inhibiting responses to the alkaloid at the highest concentration. Furthermore, the inhibitory effects of bepridil and fendiline were markedly augmented in calcium-free medium. These results clearly differentiate bepridil and fendiline from the other calcium antagonists studied. In addition they provide further evidence for effects other than at the cell membrane which could theoretically contribute to the efficacy of bepridil and fendiline as anti-anginal agents. PMID- 1893916 TI - Adenosinergic inhibition in hippocampus is mediated by adenosine A1 receptors very similar to those of peripheral tissues. AB - The amplitude of the orthodromically evoked population spike (PS) of CA1 neurons was used to investigate quantitatively adenosine receptor antagonism in guinea pig hippocampal slices. Increasing concentrations of the highly selective adenosine A1 receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX, 3-100 nM) produced parallel, rightward shifts of the dose-response curve for the N6 cyclopentyladenosine (CPA)-induced decrease in PS amplitude. Schild plot analyses of the respective antagonism data obtained in both the presence and virtual absence of endogenous adenosine yielded apparent dissociation constants (KD) of DPCPX at the hippocampal A1 receptor of 3.3 and 3.6 nM, respectively. This indicates that the inhibitory tonus generated by endogenously produced adenosine is due to tonic activation of A1 receptors. The KD values agree well with the binding affinity of DPCPX to A1 receptors determined in brain tissue sections. Since, in our preparation, Schild plot analyses of DPCPX antagonism revealed KD values close to those reported for other tissues, it is concluded that the central A1 receptor mediating adenosinergic inhibition is pharmacologically not distinct from A1 receptors identified in peripheral tissues. PMID- 1893917 TI - Airway smooth muscle selectivity of the muscarinic antagonist DAC 5945 in vivo. AB - We investigated the M3/M2 antagonist selectivity of [N-iminomethyl-N'-[(2-hydroxy 2-phenyl-2-cyclohexyl)-ethyl] piperazine HCI (DAC 5945) in vivo. ED50 values for reversal of methacholine-induced bronchoconstriction and bradycardia by muscarinic antagonists were determined in anesthetized and ventilated guinea pigs. Atropine, ipratopium, pirenzepine and diphenyl-acetoxy-4-methylpiperidine methiodide (4-DAMP) were non-selective, whereas methoctramine was cardioselective. In contrast, DAC 5945 was a more potent muscarinic antagonist in the airways than in the heart, demonstrating M3/M2 selectivity in vivo. PMID- 1893918 TI - Acute or chronic antidepressants do not modify [125I]cyanopindolol binding to 5 HT1B receptors in rat brain. AB - Acute or chronic treatment of young or adult rats with chlorimipramine, tianeptine or iprindole, antidepressants with different effects on 5-HT uptake mechanisms, did not modify the density or the affinity of 5-HT1B receptors of the frontal cortex. No significant receptor change was found after prenatal exposure to these antidepressants. The lack of effect of the antidepressants was not related to the density of 5-HT1B receptors, which was significantly lower in younger animals. PMID- 1893920 TI - Amelioration of brain damage after focal ischemia in the rat by a novel inhibitor of lipid peroxidation. AB - We studied the effects of 2-(allyl-1-piperazinyl)-4-n-amyloxyquinazoline fumarate (KB-5666) on brain edema and histological neuronal damage in rats with focal ischemia and on lipid peroxidation in brain homogenates and brain mitochondria in vitro. KB-5666 (3-100 microM) inhibited lipid peroxidation in brain homogenates and mitochondria, and also inhibited mitochondrial swelling. In a rat with middle cerebral artery occlusion, administration of KB-5666 (3 and 10 mg/kg) immediately after ischemia prevented the formation of brain edema in the cortex and ameliorated the histological neuronal damage in the same area, but failed to do so in the striatum. These results indicate that KB-5666 is a potential inhibitor of lipid peroxidation that could possibly prevent ischemic complications such as formation of brain edema and neuronal damage. Further, these results suggest that lipid peroxidation may play an important role in the pathogenesis of ischemic damage after focal ischemia. PMID- 1893919 TI - Characterization of the airway smooth muscle muscarinic receptor in vivo. AB - We examined the bronchodilator activity of eight subtype-selective and non selective muscarinic antagonists in anesthetized, ventilated guinea pigs bronchoconstricted by carbachol aerosols. Relative bronchodilator potencies were consistent with M3 receptor antagonism and correlated with inhibition of bladder smooth muscle contraction in vivo. We conclude that the airway smooth muscle muscarinic receptor can be functionally characterized in vivo as M3 and that it is of the same subtype as the muscarinic receptor in bladder smooth muscle. PMID- 1893921 TI - Age dependence of 5-methoxytryptamine-induced hindlimb scratching in rats. AB - The influence of age on hindlimb scratching induced in rats by the serotonin agonist, 5-methoxytryptamine (5-MeOT), was studied. The 5-MeOT-induced scratching was strongest in 30-day-old rats and least in 90-day-old rats. Sex hormones do not play a role in these differences since treatment of young male rats with testosterone propionate did not change the scratching response. The same age dependence was found for female rats as for males. PMID- 1893922 TI - Mechanisms of ex vivo aortic hypocontractility in endotoxemic rat. AB - To clarify the mechanism of the vascular hypocontractility in endotoxemia, the effect of endotoxin injection on phosphatidylinositol turnover and the contractile responses to NH4Cl and okadaic acid were investigated in aorta dissected from rats. The basal level of phosphatidylinositol hydrolysis and the phenylephrine- and 5-hydroxytryptamine-stimulated increase in hydrolysis were all markedly reduced in endotoxemic aortas as compared to in control aortas. Stimulation with KCl did not increase phosphatidylinositol hydrolysis in control or endotoxemic aortas. The NH4Cl-induced contractile response was significantly diminished in endotoxemic aorta, whereas the okadaic acid-induced contractile response was not altered. These results suggest that both transmembrane and intracellular signal transduction mechanisms are impaired in the endotoxemic artery whereas the contractile machinery remains intact. PMID- 1893923 TI - Endothelial nitric oxide attenuates vasoconstrictor responses to nerve stimulation and noradrenaline in the rat tail artery. AB - The effects of the nitric oxide synthesis inhibitor, NG-nitro-L-arginine (NOLA), have been examined in perfused segments of rat tail artery. NOLA (1 and 10 microM) significantly enhanced the vasoconstrictor responses to perivascular nerve stimulation (5 Hz, 10 s) and noradrenaline (10 ng). The enhancing effects of NOLA were prevented by L-arginine, but not by D-arginine, and were absent in endothelium-denuded artery segments. The results suggest that nitric oxide derived from endothelial cells attenuates vasoconstrictor responses to both nerve stimulation and noradrenaline. PMID- 1893924 TI - Diazepam-atenolol combination antagonizes aminophylline-induced convulsions and lethality in mice. AB - The present study was undertaken to identify protective drugs against aminophylline (240 mg/kg i.p.)-induced convulsions and lethality in mice. Diazepam (10 mg/kg) and valproic acid significantly prevented the convulsions, but were not effective in preventing mortality. Phenytoin, atropine, carbamazepine and atenolol were ineffective in protecting against convulsions and death. Ketamine gave partial protection against convulsions, but was not effective in preventing mortality. Diazepam (10 mg/kg) and atenolol (5 mg/kg) administered together gave total protection against convulsions and death. These results show that aminophylline-induced convulsions are relatively resistant to antiepileptic drugs, and that a combination of diazepam and a beta-blocker (atenolol) has potential as an anti-aminophylline agent. PMID- 1893925 TI - Interactions between ibogaine, a potential anti-addictive agent, and morphine: an in vivo microdialysis study. AB - Ibogaine, an indolalkylamine, has been claimed to be effective in abolishing drug craving in heroin and cocaine addicts. The present study used in vivo microdialysis to determine the effects of ibogaine on extracellular levels of dopamine (DA) and its metabolites and the effects of ibogaine pretreatment on morphine stimulation of brain DA systems. Acutely, ibogaine (40 mg/kg i.p.) decreased extracellular DA levels in the striatum, increased them in the prefrontal cortex and had no significant effects in the nucleus accumbens. Nineteen hours after ibogaine injection. DA levels were still decreased in the striatum and the metabolite levels were lower in all three regions. When injected 19 h prior to a morphine challenge (5 mg/kg i.p.), ibogaine (40 mg/kg, i.p.) prevented the rise in DA levels in all three regions normally observed after a morphine injection. A high dose of morphine (30 mg/kg i.p.), administered alone, produced no increase in extracellular DA levels; it is therefore unclear whether ibogaine antagonized or potentiated the effects of the lower dose of morphine. Regardless of the nature of this interaction, it appears that ibogaine affects brain DA systems for a period of time that exceeds its elimination from the body and, during this time, alters the responses of these systems to morphine. PMID- 1893926 TI - Effects of (S)-nafenodone, a new antidepressant, in isolated guinea-pig atrial and ventricular muscle fibres. AB - The electromechanical effects of a new antidepressant, (S)-nafenodone, were studied in isolated guinea-pig atrial and ventricular muscle fibres. In spontaneously beating right atria, (S)-nafenodone decreased the rate and amplitude of contractions and lengthened the sinus node recovery time. In electrically driven atria, the negative inotropic effect of (S)-nafenodone was less marked than that of imipramine and desipramine but similar to that of lofepramine. (S)-Nafenodone had no effect on the resting membrane potential but decreased the amplitude and maximum upstroke velocity (Vmax) both in atrial and ventricular muscle fibres; this effect was less marked than that produced by imipramine and desipramine. In atrial fibres, but not in ventricular fibres, (S) nafenodone lengthened the action potential duration, but in both tissues it increased the duration of the effective refractory period out of proportion to the change in action potential duration. Moreover, it shifted the concentration response curve for Ca2+ downwards and decreased the amplitude of the slow atrial contractions induced by histamine as well as the amplitude and Vmax of the slow action potentials induced by isoprenaline in papillary muscles. It is concluded that (S)-nafenodone exerted fewer cardiodepressant effects than imipramine and desipramine in isolated guinea-pig atrial and ventricular muscle fibres less. PMID- 1893927 TI - Cardiovascular actions of inhibitors of endothelium-derived relaxing factor (nitric oxide) formation/release in anesthetized dogs. AB - NG-monomethyl-L-arginine (NMA) and NG-nitro-L-arginine (NNA), both of which are inhibitors of nitric oxide (endothelium-derived relaxing factor, EDRF) production from L-arginine, have been shown to be pressor agents in vivo. This study compared the cardiac and vascular responses to intraaortic administration of NMA and NNA in anesthetized dogs. NMA at doses of 3, 10, 30 and 100 mg kg-1 i.a. increased systemic vascular resistance and decreased cardiac output; mean arterial pressure increased by 10 mm Hg (at 100 mg kg-1 dose). Heart rate did not change. NNA, administered at doses of 1, 3, 10 and 30 mg kg-1 i.a. produced similar cardiovascular actions and was equipotent to NMA. Pretreatment with indomethacin abolished the pressor response to NMA; however, systemic vasoconstriction and cardiac depression still occurred. Increasing mean arterial pressure by phenylephrine infusion to levels much greater than produced by NMA and NNA caused only small reductions in cardiac output. NMA did not reduce coronary blood flow, but instead caused a transient flow increase. Therefore, systemic administration of NMA and NNA result in pronounced systemic vasoconstriction and cardiac depression with only a small pressor response in anesthetized dogs. The cardiac depression did not result from elevated arterial pressure nor was it due to coronary vasoconstriction and reduced myocardial oxygen supply/demand ratio. PMID- 1893928 TI - Cardiovascular profile of the new dihydropyridine derivative S12968. AB - The cardiovascular profile of S12968 was evaluated in anaesthetized pigs, using cumulative 15-min i.v. infusions of 1.25, 2.5, 5, 10 and 20 micrograms.kg-1.min-1 (n = 7) or equal volumes of its solvent (n = 7). S12968 decreased mean arterial blood pressure from 94 +/- 4 to 66 +/- 3 mm Hg (P less than 0.05) and cardiac output from 2.7 +/- 0.2 to 2.2 +/- 0.2 l.min-1 (P less than 0.05), had no effect on heart rate and left ventricular end-diastolic pressure, but decreased maxLVdP/dt (maximal rate of rise in left ventricular pressure) by up to 35 +/- 3% (P less than 0.05). With doses higher than 10 micrograms.kg-1.min-1 transmural left ventricular blood flow increased by up to 49 +/- 22% (P less than 0.05), favouring the subepicardium over the subendocardium. Myocardial oxygen consumption decreased by 22 +/- 7 and 32 +/- 8% (P less than 0.05) during infusion of 10 and 20 micrograms.kg-1.min-1, respectively. Heart rate, left ventricular end-diastolic pressure and arterial blood pressure were not affected, but maxLVdP/dt (partially) and cardiac output returned to pre-drug values a during a 60-min post-infusion period. In conclusion, S12968 exhibited a negative inotropic effect at low doses. However, with higher doses and after discontinuation of the infusion, vasodilatation occurred, while the negative inotropy disappeared. It is possible that an active metabolite, acting preferentially on the vasculature, was responsible for the vasodilatation. PMID- 1893930 TI - Glucocorticoids induce endothelin release from vascular smooth muscle cells but not endothelial cells. AB - Vascular smooth muscle cells in culture are capable of secreting endothelin which is a vasoconstrictor and mitogenic peptide. The effect of glucocorticoids on endothelin release from vascular smooth muscle cells of the rat and rabbit aortas was investigated. Micromolar concentrations of dexamethasone and cortisol caused a 2 to 5-fold increase in endothelin release from the two smooth muscle cell types but no such response was observed in endothelial cells of the bovine aorta. Glucocorticoids appear to selectively induce endothelin release from vascular smooth muscle cells and this may be relevant to glucocorticoid-induced hypertension. PMID- 1893929 TI - Relation of anion secretory activity to intracellular Ca2+ in response to lysylbradykinin and histamine in a cultured human colonic epithelium. AB - A cultured human epithelial cell line, Colony 29, has been used to investigate the relation between anion secretion and intracellular Ca2+ concentration (Cai) in response to the secretagogues, lysylbradykinin (LBk) and histamine. Anion secretion was measured as short-circuit current (SCC) responses in epithelia cultured on previous supports. Cai was measured both in cell suspensions and epithelial monolayers using Fura-2 fluorescence. While it is concluded that raised Cai is responsible for anion secretion the relationship is complex. For both secretagogues there is a receptor reserve, that is the maximal Cai increase is greater than that required to cause a maximal secretory response. By examining the interactions between maximally effective concentrations of LBk and histamine it was shown that neither the SCC nor Cai responses behaved additively. From observations in the absence of external Ca2+ it was concluded that both secretagogues cause Ca2+ release from the same intracellular source, but that in normal conditions Ca2+ derived from intracellular and extracellular sources is responsible for the full effect. PMID- 1893931 TI - Retinoic acid modulates gap junctional permeability: a comparative study of dye spreading and ionic coupling in cultured cells. AB - All-trans retinoic acid (RA), which was recently identified as a morphogen, affects gap junctional permeability in a dose- and time-dependent manner. In five different established mammalian cell lines (FL, BRL, BICR/M1Rk, HEL37, BT5C1) 100 mumol/liter RA reduced Lucifer yellow spreading within 30 min to 20-50% of the control. Ionic coupling, however, remained almost unaffected under the same conditions. Freeze-fractured membranes of untreated and RA-treated cells were similar with regard to frequency and sizes of gap junction plaques. With concentrations of less than 10 mumol/liter RA the dye spreading increased significantly in the human amniotic cell line FL, pointing to a possible modulatory effect of RA on junctional communication. PMID- 1893932 TI - Melanin content and hydroperoxide metabolism in human melanoma cells. AB - Human melanoma cells were grown to exponential and stationary phases showing melanin contents of 4.2 +/- 0.3 and 11.3 +/- 0.6 micrograms/10(6) cells, respectively. The cells were separated in four subpopulations by a Percoll gradient; the subpopulation of density 1.07 (g/ml) was the most enriched in pigmented cells and produced 28 and 58% of the cells in exponential and stationary phases, respectively. Melanoma cells had similar superoxide dismutase and glutathione peroxidase activities in exponential and stationary phases. Moreover melanoma cells exhibited a higher catalase activity in the stationary phase: whole homogenate and cytosol activities were 7.0 +/- 0.3 and 10.8 +/- 0.6 U/mg protein, whereas in exponential phase the activities were 4.9 +/- 0.1 and 7.6 +/- 0.3 U/mg protein for whole homogenate and cytosol, respectively. The intracellular H2O2 steady-state concentration was 3.3 +/- 0.2 and 2.1 +/- 0.2 microM H2O2 for exponential and stationary phases, respectively. The spontaneous chemiluminescence of the two culture phases was 169 +/- 27 cps/10(6) cells (exponential) and 78 +/- 24 cps/10(6) cells (stationary). The cytotoxicity of H2O2 generated extracellularly by glucose oxidase was determined after 60 min of exposure. IC50 values for exponential and stationary cell cultures were 0.9 and 2.4 mU/ml of glucose oxidase, respectively. The increased catalase activities in the stationary phase as compared with the exponential phase are consistent with the decreased intracellular H2O2, with the decreased spontaneous chemiluminescence, and with the increased resistance to exogenous H2O2. PMID- 1893933 TI - Differences in laminin fragment interactions of normal and transformed endothelial cells. AB - Bovine aortic and microvascular endothelial cells showed good adhesion with spreading on fibronectin or collagen IV and to a lower extent on laminin. Recognition of native laminin was due to its long arm fragment E8 and was mediated by alpha 6 integrins as demonstrated by antibody inhibition. A considerably stronger, RGD-dependent interaction was observed with the isolated laminin short arm fragment P1 previously shown to represent a cryptic cell binding site. No adhesion was observed with the heparin-binding fragment E3. In contrast, murine microvascular endothelial cells transformed by the polyoma middle T oncogene showed preferential adherence and spreading on laminin via its E8 cell-binding site and also showed adhesion to fragment E3. Attachment to laminin fragment P1 and to collagen IV was low or negative and was never followed by spreading. These data show that the transformation of microvascular endothelial cells, which give them the property to form hemangiomas, also leads to changes in cell adhesion to extracellular matrix proteins, particularly to laminin fragments. PMID- 1893934 TI - Membrane structural dynamics of plasma membranes of living human prostatic carcinoma cells differing in metastatic potential. AB - Rigidity of the outer hemileaflet of the plasma membrane of two prostatic carcinoma cell lines with different metastatic potential, 1-LN and 1-LN-EMS-10, was assessed by steady-state anisotropy, using a battery of fluorescent probes. The "bulk" membrane rigidity sensed by diphenylhexatriene, trimethylammonio-DPH, 1-palmitoyl-2-[DPH-ethylcarbonyl]-phosphatidylcholine, and 10-pyrenedecanoic acid indicated slightly higher rigidity in the membrane of the highly metastatic line (1-LN). This was accompanied by 26% greater mole fraction of cholesterol and 9% lower phospholipid, resulting in 40% greater cholesterol/phospholipid ratio. Phosphatidylethanolamine was increased 12%, but corresponding decreases in phosphatidylserine and phosphatidylinositol resulted in no significant change in molar ratio of choline/noncholine phospholipids. Whereas unsaturation index was slightly higher in 1-LN, fatty acids of 1-LN plasma membranes contained 15% more 18:1, 43% more 20:4, 26% more 22:4, and 38% less 18:2. Anisotropy gradients were determined for the two cell lines using a series of n-(9-anthroyloxy) fatty acid probes with n = 2, 3, 6, 7, 9, 12, and 16. Gradients differed only in position of anisotropy maxima, which occurred with n = 6, in 1-LN, and n = 7, in 1-LN-EMS-10. Possible relationships between observed anisotropy gradients and differences in membrane cholesterol and fatty acid composition are discussed. PMID- 1893935 TI - Heat-induced stabilization of the nuclear matrix: a morphological and biochemical analysis in murine erythroleukemia cells. AB - Using mouse erythroleukemia cells we performed a comprehensive morphological and biochemical study of the nuclear matrix obtained after exposure of isolated nuclei to 37 degrees C or from cells heat shocked in vivo at 43 or 45 degrees C. At the ultrastructural level it was possible to see that in the absence of a 37 degrees C incubation of purified nuclei, the final matrix lacked well-defined nucleolar remnants but a peripheral lamina was clearly visible, as well as a sparse fibrogranular network which was located at the periphery of the structures. On the contrary, after a 37 degrees C nuclear incubation, very electron-dense nucleolar remnants were observed along with an abundant meshwork dispersed throughout the interior of the structures. When intact cells were heat shocked in vivo, electron-dense residual nucleoli were present only when isolated nuclei had been exposed to 37 degrees C in vitro, whereas without such an incubation, they were not as easily distinguishable and appeared less electron dense. In the latter case the inner network was more evenly distributed. After purified nuclei were incubated at 37 degrees C for 45 min, the high salt and DNase I resistant fraction retained about 18% of the nuclear protein whereas if the heating was omitted protein recovery dropped to 6%. An increase in the recovery of intact structures in the matrix fraction was the main reason for the higher protein recovery. Heating nuclei in vitro further increased the amount of nuclear protein present in the matrix fraction even if intact cells had been heat shocked in vivo. No major qualitative differences were seen when the polypeptide pattern of the various types of nuclear matrices was analyzed on one-dimensional polyacrylamide gels and this finding was further supported by Western blot analysis with a monoclonal antibody to lamins A and C. These results show that heating mainly stabilizes the nucleolar remnants of the matrix and to a lesser extent the inner network, but the morphology of the final structures is different depending on whether the stabilization is performed in vivo or in vitro. PMID- 1893936 TI - Basic fibroblast growth factor upregulates steady-state levels of laminin B1 and B2 chain mRNA in cultured neuroepithelial cells. AB - The growth of purified populations of murine neuroepithelial cells isolated from 10 day embryonic (E10) telencephalon and mesencephalon can be specifically enhanced by supplementing growth culture media with basic fibroblast growth factor (bFGF). One effect of bFGF on cultured neuroepithelial cells was to enhance the amount of laminin expressed at the protein level as detected by immunofluorescence. This was correlated with significant upregulation of steady state levels of laminin B1 and B2 chain expression as analyzed at the mRNA level. When E12 neuroepithelial cells were split into precursor neuronal or glial subpopulations on the basis of differential expression of major histocompatibility class-1 antigens, only the glial progenitor fraction was found to be capable of detectable laminin synthesis. It is thus possible that a primary action of FGF is to increase the synthesis and release of extracellular matrix molecules from neural cells which act back in a paracrine manner to stimulate differentiation. PMID- 1893937 TI - Evidence for a role of the monoclonal antibody E48 defined antigen in cell-cell adhesion in squamous epithelia and head and neck squamous cell carcinoma. AB - Monoclonal antibody (MAb) E48 recognizes a 20- to 22-kDa antigen expressed by human squamous and transitional epithelia and their neoplastic counterparts. Histochemical examination of these tissues revealed distinct surface labeling with MAb E48. To investigate the subcellular localization of the E48 antigen we have performed electron microscopical analysis. In cells of normal oral mucosa, the E48 antigen was expressed on the plasmalemma, particularly associated with desmosomes, suggesting involvement of the E48 antigen in intercellular adhesion. Furthermore, the level of expression of the E48 antigen appeared to be influenced by the cellular organization. In squamous cell carcinoma (SCC) cell lines grown in vitro as subconfluent monolayer cultures, the E48 antigen expression was low. However, E48 antigen expression increased when SCC cells were grown to confluency. E48 antigen expression was similarly high when SCC cell lines were cultured under conditions promoting three-dimensional growth either as colonies within floating collagen gels or as xenograft in tumor-bearing nude mice. Further evidence for the involvement of the E48 antigen in cell-cell adhesion was found when SCC cells were grown within collagen gels in the presence of MAb E48: no spherical colonies were formed, but cells grew out to colonies composed of single cells. Moreover, in this culture system the percentage of SCC cells growing out to colonies was decreased by the presence of MAb E48. These findings indicate that the E48 antigen is involved in the structural organization of squamous tissue and might have a role in intercellular adhesion. PMID- 1893939 TI - The cortical actomyosin system of cytochalasin D-treated lymphoblasts. AB - Global cytoskeleton dynamics is likely to exist in animal cells and some experimental evidence for this has recently been obtained in cells from the human lymphoblastic cell line KE37. We have further investigated the dramatic and reversible microtubule-dependent cell elongation which occurs upon treatment of KE37 cells with cytochalasin D. This phenomenon results in a non-locomotory cell with definite polarity. It involves a sustained equatorial myosin II-dependent contraction of cortical, most of the myosin II being accumulated on segments of the main cellular extension. We report here that such a cell lengthening is energy-dependent and can be inhibited, or suppressed, by surface ligands such as wheat germ agglutinin but not by concanavalin A. Suppression of the cytochalasin D effect by wheat germ agglutinin is rapid and appears to be collapse of the cell extension and relocalization of the contracted actomyosin as a whole. It suggests that the binding of the wheat germ agglutinin to the cell surface results in the transient disassembly of microtubules, a possibility also raised by the potent antagonist effect of taxol on wheat germ agglutinin action. Taken together, the data are consistent with a specific role of microtubules in the control of the activity of the cortical actomyosin system. PMID- 1893938 TI - Glucocorticoids induce a drastic inhibition of proliferation and stimulate differentiation of adult rat fat cell precursors. AB - The effects of physiological glucocorticoids such as cortisol and corticosterone, as well as dexamethasone, on proliferation and differentiation of rat fat cell precursors kept in primary culture were analyzed. In serum-containing medium (10%), glucocorticoids markedly decreased cell proliferation, either on subconfluent or on confluent cultures. This effect was independent of the presence of insulin. In contrast, acute amplification of adipose conversion was observed mainly when glucocorticoids and insulin were added simultaneously. Morphological quantification of lipid-containing cells confirmed acceleration of the maturation process, and an early and specific reorganization of the cytoskeleton was detected at the ultrastructural level. In the presence of insulin, glucocorticoids also enhanced the main marker enzymes, lipoprotein lipase, and glycerol phosphate dehydrogenase. Glucocorticoid effects on precursor proliferation and differentiation were clearly dose-dependent, dexamethasone being 10 times more potent than cortisol and corticosterone. Similar results were obtained in serum-free medium, as well as in preadipocyte cultures derived from different fat deposits. This study demonstrates that in addition to an acute inhibition of precursor growth, glucocorticoids exert a clear stimulation of adipose conversion, which depends mainly on the presence of insulin and the glucocorticoid concentration. PMID- 1893940 TI - Developmental kinetics of hemopoietic progenitors in the avian embryo spleen. AB - By means of plasma clot clonal cultures, the content of the avian spleen in granulomonocytic progenitors was studied during ontogeny. Serum-free media were used that were supplemented with growth activities produced either by embryonic fibroblasts or adult spleen cells. These two conditioned media not only permitted the growth of M-CFC, G-CFC, and GM-CFC but also F-CFU (fibroblast colony-forming units) from quail or chick embryonic spleen cells. The presence of spleen cell conditioned medium promoted the development of large colonies of immature granulocytes. In the chick the first hemopoietic progenitors appeared at E9 and their number displayed two peaks, one at E15 and a smaller one at E18. In the quail the first progenitors were detected as early as E7 and their number peaked at E10. In this species, hemopoietic progenitors disappeared definitively before hatching while in the chick some were still present at P3. The progenitor content of the chick embryo spleen was compared to that of the bone marrow. This content remained stable during all of embryonic life, while the bone marrow exhibited a very different profile, where a sharp peak at E16 was followed by an acute decline and a stabilization at a rather low level. The particular profile in the spleen speaks in favor of a special role of this organ in the development of the hemopoietic system. PMID- 1893941 TI - Isolation and characterization of an established endothelial cell line from transgenic mouse hemangiomas. AB - A murine endothelial cell line was isolated from hemangiomas induced by expression of the polyoma early region gene in transgenic mice. After two cell sortings using acetylated low-density lipoprotein with a fluorescent label (Dil Ac-LDL), a pure population of endothelial cells has been carried for more than 60 passages from the animal. The cells retain endothelial cell properties such as a characteristic cobblestone appearance at confluency, contact-inhibited growth, and active uptake of Ac-LDL. Expression analysis shows that the cells express both the polyoma transgene and the von Willebrand factor, an endothelial cell marker. Subcutaneous injection of the cultured endothelial cells into nontransgenic histocompatible mice or nude mice led to hemangioma formation, and endothelial cells were re-isolated by cell sorting from these secondary hemangiomas. This cell line represents a renewable source of murine endothelial cells derived from transgenic mice that can be studied both in vitro and by reintroduction into a host. PMID- 1893942 TI - v-myb transformation of Xeroderma pigmentosum human fibroblasts: overexpression of the c-Ha-ras oncogene in the transformed cells. AB - Human Xeroderma pigmentosum "normal" fibroblasts AS16 (XP4 VI) were transformed after transfection with a recombinant v-myb clone. In this clone (pKXA 3457) derived from avian myeloblastosis virus (AMV), the expression of the oncogene sequences is driven by the AMV U-5 LTR promoter. The transformed cells (ASKXA), which have integrated a rearranged v-myb oncogene, grow in agar, are not tumorigenic in nude mice, and express a 45-kDa v-myb protein. The HMW DNA of these cells transform chicken embryo fibroblasts. The c-Ha-ras oncogene is overexpressed in the ASKXA cells but not in the parental "normal" AS16 cells and a revertant clone (ASKXA Cl 1.1 G). Our results lead to the conclusion that the XP fibroblasts are phenotypically transformed by the presence of the transfected v-myb oncogene, which is able to induce an overexpression of the c-Ha-ras gene. PMID- 1893943 TI - Histone acetylation reduces H1-mediated nucleosome interactions during chromatin assembly. AB - During chromatin replication and nucleosome assembly, newly synthesized histone H4 is acetylated before it is deposited onto DNA, then deacetylated as assembly proceeds. In a previous study (Perry and Annunziato, Nucleic Acids Res. 17, 4275 [1989]) it was shown that when replication occurs in the presence of sodium butyrate (thereby inhibiting histone deacetylation), nascent chromatin fails to mature fully and instead remains preferentially sensitive to DNaseI, more soluble in magnesium, and depleted of histone H1 (relative to mature chromatin). In the following report the relationships between chromatin replication, histone acetylation, and H1-mediated nucleosome aggregation were further investigated. Chromatin was replicated in the presence or absence of sodium butyrate; isolated nucleosomes were stripped of linker histone, reconstituted with H1, and treated to produce Mg(2+)-soluble and Mg(2+)-insoluble chromatin fractions. Following the removal of H1, all solubility differences between chromatin replicated in sodium butyrate for 30 min (bu-chromatin) and control chromatin were lost. Reconstitution with H1 completely restored the preferential Mg(2+)-solubility of bu-chromatin, demonstrating that a reduced capacity for aggregation/condensation is an inherent feature of acetylated nascent nucleosomes; however, titration with excess H1 caused the solubility differences to be lost again. Moreover, when the core histone N-terminal "tails" (the sites of acetylation) were removed by trypsinization prior to reconstitution, H1 was unable to reestablish the altered solubility of chromatin replicated in butyrate. Thus, the core histone "tails," and the acetylation thereof, not only modulate H1-mediated nucleosome interactions in vitro, but also strongly influence the ability of H1 to differentiate between new and old nucleosomes. The data suggest a possible mechanism for the control of H1 deposition and/or chromatin folding during nucleosome assembly. PMID- 1893944 TI - Expression of stress fibers in bullfrog mesothelial cells in response to tension. AB - The relationship between stress fibers and tension in mesothelial cells of the bullfrog small intestine was examined by fluorescence cytochemistry using en face mesothelial cell preparations. In nontreated controls, actin revealed by rhodamine-phalloidin staining was localized only along the margins of the mesothelial cells. On the other hand, many stress fibers were formed in the mesothelial cells within 5-7 min after stretching of the intestinal wall in a given direction. The orientation of stress fibers within the cells was coincident with the direction of the tension applied. These cytoplasmic fibers disappeared almost completely from the mesothelial cells within 30 min after the release of tension. According to a difference in the intensity of tension necessary for stress fiber expression, the intestinal mesothelial cells were classified into two groups. Furthermore, cells containing stress fibers in each group showed a rapid increase in number once a given value of tension was applied. The present results indicate that the mesothelial cells of bullfrog small intestine may develop stress fibers to counteract tension exerted on the intestinal wall. Such stress fibers may serve to maintain cellular integrity by strengthening the cellular attachment to subepithelial tissue. PMID- 1893945 TI - Basal and ATP-stimulated phosphoinositol metabolism in fusing rat skeletal muscle cells in culture. AB - A considerable rise in inositol phosphates was observed at the beginning of myoblast fusion. Extracellular ATP, through P2-purinergic receptors, induced inositol phosphate accumulation before and after fusion; however, no effect of ATP on phosphoinositol levels could be detected during the period of fusion. The possibility of ATP being a fusion signal is discussed. PMID- 1893946 TI - Biological effects of recombinant erythropoietin, granulocyte-macrophage colony stimulating factor, interleukin 3, and interleukin 6 on purified rat megakaryocytes. AB - The biological effects of recombinant hematopoietic factors, which are considered to stimulate megakaryocytopoiesis in vitro or in vivo, were studied utilizing purified rat megakaryocytes. Recombinant human erythropoietin (rhEPO), recombinant murine granulocyte-macrophage colony-stimulating factor (rmGM-CSF), and recombinant murine interleukin 3 (rmIL-3) stimulated both [3H]thymidine and [3H]leucine incorporation into purified rat megakaryocytes. In contrast, recombinant human interleukin 6 (rhIL-6) did not stimulate [3H]thymidine uptake but did increase [3H]leucine incorporation into purified rat megakaryocytes. These in vitro data suggest that DNA synthesis in megakaryocytes may be regulated by EPO, GM-CSF, and IL-3, and that protein synthesis is stimulated by EPO, GM CSF, IL-3, and IL-6 in vitro. PMID- 1893947 TI - The effects of x-irradiation on hematopoietic stem cell compartments in the mouse. AB - The sensitivity for x-irradiation of a series of hematopoietic stem cell populations has been determined. The most primitive cells identified, cells with marrow-repopulating ability (MRA), showed the highest degree of radioresistance. These MRA cells which generate many secondary day-twelve spleen colony-forming units (MRA[CFU-S-12]) or colony-forming units in culture (MRA[CFU-C]) in the marrow of primary recipients had Do values equal to 1.18 and 1.13 Gy, respectively. The more mature CFU-S-12 had intermediate radiosensitivity (Do = 0.94 Gy), whereas the less primitive CFU-S-7 were the most radiosensitive (Do = 0.71 Gy). The in vitro colony-forming precursor cells (CFU-C) showed low radiosensitivity. These data clearly show that the most primitive hematopoietic stem cell measured is less sensitive to ionizing radiation than generally has been assumed on the basis of measurements on CFU-S-7 or CFU-S-12. PMID- 1893948 TI - Administration of an immunomodulatory azaspirane, SK&F 105685, or human recombinant interleukin 1 stimulates myelopoiesis and enhances survival from lethal irradiation in C57Bl/6 mice. AB - The immunomodulatory azaspirane SK&F 105685 has immunosuppressive activity in animal models of autoimmune disease such as adjuvant-induced arthritis and experimental autoimmune encephalomyelitis. The mechanism of SK&F 105685 appears to be the induction of nonspecific suppressor cell (SC) activity. SC appear to be "null cells," that is, cells that lack specific cell surface markers of mature B cells, T cells, natural killer (NK) cells, or macrophages. Because we hypothesized that the induction of SC was associated with enhanced hematopoiesis, we sought to determine the hematopoietic potential of SK&F 105685. Recombinant interleukin 1 alpha (rIL-1) was included as a positive control for hematopoietic stimulation in our studies. We demonstrate here that administration of SK&F 105685 increases the number of granulocyte-macrophage colony-forming units (CFU GM) within the bone marrow 24 h after injection in a dose-dependent manner. In addition, the percentage of CFU-GM in S-phase of the cell cycle was significantly increased, as was colony-stimulating activity (CSA) present in the serum of treated animals. In our experiments IL-1 did not increase marrow CFU-GM; however, splenic CFU-GM, the proportion of CFU-GM in S-phase of the cell cycle, and serum CSA were all increased 24 h after a single treatment. Administration of SK&F 105685 24 h prior to lethal irradiation resulted in a dose-related increase in the number of surviving mice. These results demonstrate that SK&F 105685 and rIL 1 stimulate myelopoiesis in vivo and suggest a mechanism by which prophylactic treatment with these agents protects mice from otherwise lethal irradiation. PMID- 1893950 TI - Hematopoietic stem cells in +/+, nu/+, and nu/nu C57Bl/10 mice. AB - Mice with the nu mutation have been shown to have a reduced incidence of spleen colony-forming units (CFU-S), with a higher variability between individual mice compared to +/+ mice. The presence of these defects also in nu/+ mice indicates that this mutation is a codominant trait and that the hematopoietic changes may not be solely caused by thymus dysgenesis. The proportion of CFU-S synthesizing DNA (approximately 40%) has not been significantly different between +/+, nu/+, and nu/nu mice. PMID- 1893949 TI - In vivo stimulation of platelet production in a primate model using IL-1 and IL 3. AB - The in vivo administration of various cytokines for hematopoietic stimulation has led primarily to the enhancement of the myeloid response with an insignificant contribution toward stimulating any increase in platelet production. Current studies have suggested that interleukin 1 (IL-1) and interleukin 3 (IL-3) are two of several factors that have an effect on either megakaryocyte formation or platelet production. The objective of our research was to investigate how the in vivo administration of IL-1 or IL-3 or a combination could be used to regulate megakaryocytopoiesis and platelet production in nonhuman primates. A single dose of IL-1 was able to stimulate an increase in platelet production for 3 weeks. The response was shown to be biphasic, with increased platelet counts of 46% and 49% above baseline on days 8 and 17, respectively. In contrast, the administration of IL-3 for 6 days led to an increase of 29% above baseline on day 17. An interesting observation was that the increased platelet counts were accompanied by a transient increase in the peripheral blood of a highly proliferative megakaryocyte colony-forming cell (MK-CFC), which attained a maximum concentration on day 7. The administration of a sequential combination of IL-1, then IL-3, was further evaluated to elucidate a possible potentiation on platelet production. The result was a similar increase in platelets to that observed in IL 1-only-treated monkeys for the first 7 days. However, the most significant effect was observed on day 17, when the 85% increase in platelets was demonstrated to be additive of the single-agent effects on that day. A reversal in the order of cytokine administration did not affect platelet production in this manner. In IL 1, then IL-3-treated monkeys, the increased platelet counts were also accompanied by an increase in the concentration of the peripheral blood MK-CFC from days 7 through 14. These results demonstrate that a combination of factors may be required to enhance platelet production, stimulating not only the formation of megakaryocytes but also stimulating the production and release of platelets into the peripheral blood. PMID- 1893951 TI - The hematopoietic and mature blood cells of the rat: their morphology and the kinetics of circulating leukocytes in control rats. AB - Although the morphology of the hematopoietic and circulating blood cells of the rat differs slightly from that of human blood cells, the basophil is the only human blood cell for which the rat does not have a readily recognizable counterpart. The morphological classification of the rat's marrow and peripheral blood cells as based on our experience is described with reference to the differing observations of previous investigators and with comparison to the human hematopoietic system. Examination of the bone marrow and peripheral blood demonstrated that control rats injected i.v. with 1% normal rat serum in sterile saline exhibit a moderate transient lymphopenia as the only significant hematologic fluctuation induced by the stresses of injection, general anesthesia, and tail bleeding. Morphologic quantitation of marrow and peripheral blood cells complements the insights obtained by the culture of marrow cells. An appreciation of the morphology of the rat's blood cells and of the reproducible and quantitative nature of marrow and peripheral blood smear examinations may lead to more in vivo investigations of hematopoiesis and leukocyte trafficking. PMID- 1893952 TI - Protection of zidovudine-induced toxicity against murine erythroid progenitor cells by vitamin E. AB - The ability of vitamin E (alpha-tocopherol) to stimulate erythroid progenitor cells was investigated in an attempt to identify ways to ameliorate zidovudine (azidothymidine, AZT)-induced anemia. In vitro, alpha-tocopherol acid succinate (ATS), upon incubation with murine bone marrow cells at concentrations of up to 4 micrograms/ml, caused a dose-dependent increase in erythroid colony-forming unit (CFU-E)-derived colonies. This increase was equivalent to the effect demonstrated by 50 mU of recombinant human erythropoietin (rhEpo) or 200 U of recombinant interleukin 3 (rIL-3). For in vivo studies, anemia was produced in CD-1 male mice by administering AZT in drinking water (1.5 mg/ml). Treatment with vitamin E (50 mg/kg body weight) or Epo (0.4 U per mouse) was initiated 24 h later and continued for five consecutive days. Seventh day bone marrow cells from femurs were assayed for CFU-E-derived colonies. Both vitamin E and Epo significantly increased the number of CFU-E-derived colonies by 75% and 86% of control, respectively, indicating that these agents were approximately similar in protecting the bone marrow from AZT-induced toxicity. PMID- 1893953 TI - Differential effect of interleukin 3 on the metabolism of high-dose cytosine arabinoside in normal versus leukemic human bone marrow cells. AB - We have examined the effect of recombinant interleukin 3 (rIL-3) on the metabolism of high-dose cytosine arabinoside (Ara-C), an S-phase-specific agent, in normal human bone marrow mononuclear cells (BMMC) and leukemic blasts from patients with acute myeloid leukemia (AML). Exposure to rIL-3 for 24 h significantly increased the percentage of cycling S-phase cells in normal BMMC as well as leukemic cells. A concomitant expansion of intracellular deoxycytidine triphosphate (dCTP) levels occurred to a significantly greater extent in normal BMMC. Compared to treatment with Ara-C (10 mumol/liter) alone, prior and coadministration of rIL-3 with Ara-C increased Ara-CTP levels in leukemic blasts. However, an identical treatment produced significantly higher dCTP levels in normal BMMC, resulting in a significantly lower mean Ara-CTP to dCTP pool ratio in normal BMMC compared to that observed in each of the samples of AML blasts. Following treatment with Ara-C plus rIL-3 versus Ara-C alone, the alteration in Ara-C DNA incorporation corresponded with the change in Ara-CTP to dCTP ratio observed in normal BMMC and AML blasts. The differential effect of rIL-3 on the metabolism of high-dose Ara-C in normal versus leukemic cells may indicate a role for rIL-3 in enhancing the selectivity of Ara-C toward leukemic myeloblasts. PMID- 1893954 TI - Effects of recombinant human cytokines on precursor-B acute lymphoblastic leukemia cells. AB - An in vitro colony assay was used to examine the growth stimulatory effects of a variety of recombinant human lymphohemopoietic cytokines on human precursor-B acute lymphoblastic leukemia (ALL) cells. Of 23 cases evaluated, 16 formed significant numbers of colonies (mean 280, range 36-939) when cultured in 10% fetal calf serum in 0.8% methylcellulose containing 10% partially purified B-cell growth factor (BCGF). Immunoperoxidase staining of cells from cultures confirmed a precursor-B phenotype (HLA-DR+, CD-10+, CD-19+, CD-34+, Ig-, CD-3-, CD-11C-). When these cases were cultured with recombinant human cytokines (but without BCGF) only a minority showed colony formation, in all instances less than seen with BCGF. Three cases were stimulated both by interleukin 3 (IL-3) and the putative pre-B growth factor interleukin 7 (IL-7). One case was stimulated both by tumor necrosis factor alpha and by interleukin 6 (IL-6); these results were confirmed on highly purified CD-10+, CD-19+ cells prepared by fluorescence activated cell sorting. A further case was stimulated by granulocyte-macrophage colony-stimulating factor (GM-CSF), including CD-10+, CD-19+ purified cells. All cases responding to recombinant cytokines were heavily pretreated patients at relapse, whereas none of the newly diagnosed untreated cases showed any response. These results confirm that activities present in BCGF are the major stimulant for precursor-B ALL proliferation in vitro. None of the recombinant cytokines examined, including IL-7, appeared to have consistent activity under these culture conditions. The molecules regulating growth of ALL remain to be more precisely defined. PMID- 1893955 TI - Latent deficiency of the hematopoietic microenvironment of aged mice as revealed in W/Wv mice given +/+ cells. AB - The macrocytic anemia of W/Wv mice can be cured by injection of +/+ bone marrow cells (BMC) from WBB6F1 mice. However, it has been observed that some W/Wv recipients appear to "lose" their cure with time, an effect that does not appear to be related to the age of the BMC donor. The present study was undertaken to determine the effect of recipient age on W/Wv responses to BMC injection. The effect of aging on erythroid parameters was similar in untreated W/Wv mice and +/+ controls. In both genotypes, hematocrit (HCT) and red blood cell count (RBC) decreased, and the modal red blood cell size (peak) increased between 13 and 150 weeks of age. As anticipated, mean HCT and RBC values were lower and peak values higher in W/Wv mice compared to +/+ controls at every age. However, the rate of decrease in HCT and RBC with age was the same for both genotypes, suggesting that the age effect and W gene effect were independent. Peak values increased slightly more with age for W/Wv than for +/+ controls. When female W/Wv mice in three age groups (23.5, 70, and 91.5 weeks old) were injected with 5 x 10(5) BMC from 20 week-old +/+ female donors and HCT, RBC, and peak were determined monthly, improvement was seen in most W/Wv recipients. However, in the older mice this improvement was slower and often was not sustained; 100% of the youngest recipients, 80% of the middle-aged, and only 30% of the older groups were cured after 3 months. Taken together, these data suggest a latent deficiency of the aging hematopoietic microenvironment that is revealed in W/Wv mice by the stress of continuing erythroid demand on the limited number of normal donor BMC. PMID- 1893956 TI - Influence of T-lymphocytes and lactoferrin on the survival-promoting effects of IL-1 and IL-6 on human bone marrow granulocyte-macrophage and erythroid progenitor cells. AB - Purified recombinant human (rhu) interleukin (IL)-1 alpha, rhuIL-6, iron saturated lactoferrin (LF), and T-lymphocytes were assessed for their effects on the survival of granulocyte-macrophage (granulocyte-macrophage colony-forming units, CFU-GM) and erythroid (erythroid burst-forming units, BFU-E) progenitor cells from human low-density (LD) and nonadherent LD T-lymphocyte-depleted (NALT ) bone marrow (BM) cells. Colony-stimulating factor (CSF) deprivation studies showed that 10 ng/ml IL-1 alpha could promote the survival of CFU-GM and BFU-E from NALT- BM cells. Concentrations of 1 ng/ml IL-1 alpha and 1-100 ng/ml IL-6 alone could not promote progenitor cell survival from NALT- BM cells; however, concentrations of 1 ng/ml each of IL-1 alpha and IL-6 could synergize to promote the survival of CFU-GM but not of BFU-E. The combination of these low concentrations of IL-1 alpha and IL-6 could, however, support the survival of BFU E in the presence of purified T-lymphocytes. LF could decrease the survival of CFU-GM and BFU-E from LD but not from NALT- BM cells, apparently due to the inhibition of IL-1 release from monocytes in this cell population. The suppressive effect of LF on the survival of those progenitor cells was abolished by concentrations of 10 ng/ml IL-1 alpha or 1 ng/ml each of IL-1 alpha and IL-6. These results demonstrate that the survival of human marrow CFU-GM and BFU-E can be influenced by IL-1, IL-6, LF, and T-lymphocytes. PMID- 1893957 TI - Streptavidin-biotin immunotoxins: a new approach to purging bone marrow. AB - Immunotoxins have been used both experimentally and clinically to purge bone marrow of tumor cells or T cells before transplantation. We describe the synthesis of a streptavidin-biotin-toxin conjugate using whole ricin. Streptavidin-biotin-ricin (SA-BR) conjugates were synthesized by biotinylation of whole ricin, which was then complexed with streptavidin. Hybrid molecules consisting of a single biotinylated ricin moiety linked to a streptavidin molecule were separated by gel filtration. This SA-BR conjugate was used in an indirect cytotoxicity assay. The assay involved sensitizing of target cells with biotinylated monoclonal antibody (B-MCAB) followed by treatment with dilutions of SA-BR conjugate. The assay demonstrated a specific antibody-directed cytotoxicity. The strength of this SA-BR system is that a single conjugate was able to be used in conjunction with a library of B-MCABs to selectively target phenotypically different cell types. The application of the SA-BR conjugate is thus only restricted by the availability of B-MCABs specific for the desired target cells. The high affinity of avidin for biotin (Kd approximately 10(-15)) and the ability of a single conjugate to target phenotypically different cells through utilization of a library of B-MCABs gives SA-BR conjugates great potential in the selective targeting of individual cell types. PMID- 1893958 TI - Is thrombopoietin interleukin 6? AB - Recent data concerning to ability of interleukin 6 (IL-6) to stimulate platelet production have raised the possibility that platelet production is not specifically regulated by a unique feedback mechanism, but is part of a network encompassing several hemopoietic growth factors. Hypotheses are presented about the nature of thrombopoietin, its relationship to known growth factors, especially IL-6, and the specificity of a thrombopoietic response following change in the circulating platelet mass. PMID- 1893959 TI - Long-term culture of human bone marrow. I. Characterization of adherent cells in flow cytometry. PMID- 1893960 TI - New hats for hematopoietic hormones. PMID- 1893961 TI - Complement depletion in vitro limits monoclonal antibody 6-19-dependent complement-mediated killing of tumor cells in bone marrow. AB - Selective killing of nonhematopoietic tumor cells in bone marrow harvested for autologous bone marrow transplantation was studied using cultured neuroblastoma cells, monoclonal antibody 6-19, and baby rabbit serum as a source of complement. Monoclonal antibody 6-19, a murine IgG2a antibody, was selected for binding to a cell surface antigen on cultured human neuroblastoma cells that is not expressed by hematopoietic cells. The antigen is an 80-kd sialoglycoprotein present on a wide variety of nonhematopoietic tumors, and it is expressed by normal fibroblast and endothelial cells. The effect of the presence or absence of bone marrow mononuclear cells on target cell survival was evaluated using Hoechst 33342 stained neuroblastoma cells, trypan blue exclusion, and fluorescence microscopy. More than 4 logs of neuroblastoma cells were destroyed in the presence of a more than tenfold excess of bone marrow cells following two incubations with monoclonal antibody 6-19 and complement for 30 min at 37 degrees C. Monoclonal antibody concentrations greater than 5-10 micrograms/ml did not increase cell lysis. The destruction of tumor cells was limited by depletion of complement activity. Tumor cell killing increased with complement concentration and incubation duration but there was no additional cell lysis with incubations greater than 30 min. The percentage of target cells killed was significantly decreased when the target cells were treated in the presence of increasing concentrations of bone marrow mononuclear cells. This decrease in target cell destruction is a result of additional depletion of complement activity by bone marrow mononuclear cells. These results suggest that optimal purging of tumor cells by antibody and complement will be achieved following multiple brief incubations with fresh antibody and complement. PMID- 1893962 TI - Age-related changes in various hemopoietic progenitor cells in senescence accelerated (SAM-P) mice. AB - The effect of aging process on the hemopoietic system in senescence-accelerated (SAM-P) mice with respect to numbers of hemopoietic progenitor cells was investigated. The numbers of femoral granulocyte-macrophage colony-forming cells (CFU-GM), mast cell progenitors (mast colony-forming units, CFU-Mast), erythroid burst-forming units (BFU-E), and erythroid colony-forming units (CFU-E) in old mice (30-35 weeks old) decreased to 96%, 81%, 83%, and 87% of those of young mice (8-12 weeks old), respectively. The numbers of femoral fibroblast colony-forming cells (CFU-F) in old mice increased to 315% of those of young mice. The numbers of splenic CFU-GM, CFU-Mast, BFU-E, and CFU-E in old mice decreased to 7%, 43%, 25%, and 40% of those of young mice, respectively. In contrast, significant changes in these progenitor cells were not observed in the bone marrow. These findings suggest that the effect of the aging process on hemopoietic tissues in SAM-P mice is predominantly in the spleen. PMID- 1893963 TI - The development of thermotolerance in bone marrow CFU-S during chronic hyperthermia. AB - The purpose of this investigation was to study the response of the hematopoietic stem cell, spleen colony-forming unit (CFU-S), to hyperthermia. We have shown that CFU-S can acquire a transient resistance to further heating (thermotolerance). Hyperthermia was applied in vitro to nucleated bone marrow cells in McCoy's 5A medium plus 15% fetal bovine serum. Day-10 CFU-S (CFU-S10) were detected as spleen colonies after inoculation into the tail vein of irradiated (450 cGy plus 4 h plus 400 cGy) Balb/c male mice. Thermotolerance development was detected with a "step-up" heating protocol consisting of heating for various times at 42 degrees C followed immediately with a thermal challenge of 26 min at 44 degrees C. The inverse of the slopes of the heat "dose-response" curves (D degree +/- SE) of the normotolerant CFU-S heated to 42 degrees, 42.5 degrees, 43 degrees, 43.5 degrees, and 44 degrees C were 108 +/- 13, 54 +/- 8, 25 +/- 1, 17 +/- 2, and 12 +/- 5 min, respectively. A plot of the slopes of the heat "dose-response" relationships versus the inverse of the absolute temperature (Arrhenius plot) showed an inflection at approximately 43 degrees C. Analysis of the regression coefficient above and below the inflection point (Arrhenius analysis) yielded inactivation enthalpies (+/- SE) of 598 +/- 130 kJ/mol (143 +/- 31 kcal/mol) and 1205 +/- 171 kJ/mol (288 +/- 41 kcal/mol), respectively. The difference in inactivation enthalpy indicates a change in mechanism in the thermal inactivation of CFU-S above and below 43 degrees C, possibly due to thermotolerance development during exposure to temperatures less than 43 degrees C. Prolonged incubation at 42 degrees C for up to 180 min with a step-up to 44 degrees C for 26 min showed that CFU-S survival increased rapidly from 0.25 (26 min at 44 degrees C) to 0.52 within 10 min. The thermotolerance ratio (TTR, ratio of the surviving fraction of the maximum thermotolerant cells to that of the normotolerant cells) was 2.1. Both the higher inactivation enthalpy for exposures less than 43 degrees C and the rapid increase in survival during the "step-up" heating experiments at 42 degrees C demonstrate that CFU-S can develop thermotolerance during prolonged hyperthermia. These results suggest that thermotolerance can influence the thermal response of pluripotent bone marrow stem cells heated during whole-body or local-regional clinical hyperthermia protocols. PMID- 1893964 TI - Rapid and sensitive mRNA phenotyping for interleukins (IL-1 to IL-6) and colony stimulating factors (G-CSF, M-CSF, and GM-CSF) by reverse transcription and subsequent polymerase chain reaction. AB - Oligonucleotide primer pairs specific for interleukins (IL)-1 alpha, IL-1 beta, IL-2, IL-3, IL-4, IL-5, and IL-6, as well as for granulocyte colony-stimulating factor (G-CSF), macrophage colony-stimulating factor (M-CSF), and granulocyte macrophage colony-stimulating factor (GM-CSF) mRNA/cDNA were synthesized in order to detect cytokine transcripts by reverse transcription and subsequent polymerase chain reaction (RT/PCR). Analysis of RNA preparations of the human bladder carcinoma cell line 5637 by this methodology reveals expression of mRNAs for IL-1 alpha, IL-1 beta, IL-6, G-CSF, M-CSF, and for GM-CSF, whereas mRNAs for IL-2, IL 3, IL-4, and IL-5 are not detectable. These results are in agreement with data obtained by classical methods. Thus, for the cytokines IL-2, IL-3, IL-4, and IL 5, it was not possible to detect a phenomenon described as 'illegitimate transcription,' defined as the low level transcription of any gene in any cell type. This finding is of importance for the applicability of mRNA phenotyping employing RT/PCR for the determination of mRNA expression patterns. For M-CSF mRNA detection, two oligonucleotide primer pairs had to be used to distinguish between the alpha-(pcCSF17) and beta-splicing forms and to overcome the problem of non-amplification of a larger fragment in the presence of a competing smaller one, defined here as 'incomplete positivity.' For G-CSF, IL-4, IL-2, and IL-5, RT/PCR reveals two fragments. Restriction enzyme analysis of the additional fragments suggests that they may arise from alternative splicing events. For G CSF and IL-4, exons 3 and 2 seem to be spliced out, respectively. The additional fragments for IL-2 and IL-5 RT/PCR have not yet been further characterized, but the size of the fragments makes it seem probable that exons 2 and 3 are spliced out for IL-2 and IL-5, respectively. The biological role of these alternative mRNAs has yet to be determined. PMID- 1893965 TI - Erythroid progenitors in polycythemia vera demonstrate a different response pattern to IL-4 compared to the normal BFU-E from peripheral blood. AB - Human recombinant interleukin 4 (IL-4) was studied for its effects on erythroid burst-forming units (BFU-E) from normal peripheral blood and from patients with polycythemia vera (PV). IL-4 enhanced the proliferation of normal peripheral blood BFU-E (183% +/- 20% enhancement), whereas in the presence of interleukin 3 (IL-3) no further augmentation was noticed. The IL-4-mediated effects were independent of the absence or presence of adherent cells, B cells, or T cells. These data are in contrast with results obtained from normal human bone marrow cells, in which IL-4 antagonized the enhancing effects of IL-3. In PV a different response pattern was observed. The effects of IL-4 on the erythropoietin (Epo) independent BFU-E were variable. In five PV patients no suppressive or enhancing effects of IL-4 were observed, whereas in two additional patients a significant decline in the Epo-independent BFU-E was noted. In the presence of IL-3, IL-4 significantly antagonized the IL-3-supported Epo-independent BFU-E in all patients (272% +/- 57% vs 187% +/- 49% enhancement, p less than 0.05). In contrast, IL-4 did not modify the IL-3-supported Epo-dependent BFU-E. In summary, these data suggest a difference between the normal and PV peripheral blood BFU-E. The Epo-dependent erythroid progenitors in PV patients showed a response pattern with IL-3 and IL-4 comparable to that of normal peripheral blood BFU-E, whereas the Epo-independent erythroid progenitors behaved like normal human bone marrow BFU-E, suggesting a shift in the stem cell compartment in PV. This is further supported by the finding that erythroid colony-forming units (CFU-E), normally only present in the bone marrow, could be cultured from the peripheral blood of PV patients in the presence or absence of Epo. PMID- 1893966 TI - Effects of ubenimex on erythroid progenitors (CFU-E and BFU-E) in human bone marrow. AB - Ubenimex (UBX, bestatin) is known to be an immunomodulator and host-mediated antineoplastic agent. Effects of UBX on human bone marrow erythroid progenitors (erythroid colony-forming units, CFU-E; and erythroid burst-forming units, BFU-E) were investigated in vitro. UBX enhanced CFU-E and BFU-E growth in the nonseparated bone marrow mononuclear cell fraction at concentrations from 0.005 to 5 micrograms/ml. The enhancements of CFU-E and BFU-E were independent of the concentration of erythropoietin added to culture system. In the T-cell-depleted bone marrow fraction, UBX also increased CFU-E and BFU-E growth, but it failed to stimulate these cells in the nonphagocytic and nonadherent bone marrow fraction. These findings indicate that UBX may stimulate erythroid progenitors mediated through monocytes and macrophages. PMID- 1893967 TI - Effects of interleukin 4 on stromal cell-associated bone marrow culture. AB - We examined the effect of murine interleukin 4 (IL-4) on in vitro hemopoiesis associated with an endothelial-adipose cell line derived from a murine bone marrow stroma and termed 14F1.1. The addition of IL-4 to the co-culture led to the rapid disappearance of hemopoietic progenitors, and when greater than or equal to 20 U/ml IL-4 was added, this effect became remarkable. The stimulation of 14F1.1 cells by IL-4 before the start of co-culture accelerated the disappearance of hemopoietic progenitors, although continuous stimulation by IL-4 was needed. When IL-4 was added to the co-culture 2 weeks after initial incubation, the myeloid lineage progenitor cells disappeared within 1 week. When we examined whether the inhibitory activity on hemopoiesis was induced by 14F1.1 cells stimulated with IL-4, we found no distinct inhibitory activity in the 14F1.1-cell supernatant, but there was a slight increase in colony-stimulating activity. Colony formation of bone marrow cells seeded on top of 14F1.1 cells but separated by a thin 'empty' agar layer was enhanced by IL-4-treated 14F1.1 cells. We also noted the disappearance of the 'cobblestone' area, which had been the site of active hemopoiesis in this culture, together with the disappearance of any granulocyte-macrophage colony-forming units (CFU-GM), thereby implying that IL-4 alters the interaction between hemopoietic progenitors and stromal cells. PMID- 1893968 TI - Uteroferrin: a progesterone-induced hematopoietic growth factor of uterine origin. AB - Uteroferrin is a purple progesterone-induced glycoprotein containing two molecules of iron per 35,000 molecular weight polypeptide, which has high amino acid sequence homology with Type 5 acid phosphatases from normal human placentae, from sera of patients with hairy cell leukemia, Gaucher's disease, and osteoporosis, as well as from normal spleens of pigs, cattle, rats, and mice. Results of the present study indicate that uteroferrin also has colony-forming unit (CFU) activity for committed erythroid (BFU-E) and granulocyte monocyte/macrophage (CFU-GM) cell lines and exists as far back as the granulocyte, erythrocyte, monocyte/macrophage, megakaryocyte (CFU-GEMM) committed lineage. Uteroferrin exerts maximum CFU activities at 1 microgram/ml in serum free culture medium with no supplemental iron (90 micrograms/ml ferric iron). However, when ferric iron concentration in medium was increased to 200 micrograms/ml, uteroferrin had maximum CFU activities at 100 pg/ml. Preincubation of uteroferrin with polyclonal antiserum or monoclonal antibody to uteroferrin effectively eliminated its CFU activities. Uteroferrin derived from human term placentae also exhibits BFU-E, CFU-GM, and CFU-GEMM activities. The mechanism by which uteroferrin stimulates proliferation and differentiation of primitive hematopoietic stem cells is unclear. PMID- 1893969 TI - Characterization of platelet function in cyclic hematopoietic dogs. AB - Platelet aggregation to incremental doses of eight different platelet agonists (collagen, thrombin, platelet-activating factor [PAF], arachidonic acid [AA] plus epinephrine, the calcium ionophore A23187, ADP, phospholipase C [PLC], and 12-O tetradecanoyl phorbol-13-acetate [TPA]) was compared in normal (N) and cyclic hematopoietic (CH) dogs. Platelet aggregation was defective with collagen, PAF, TPA, and possibly thrombin as agonists but normal when ADP, PLC, arachidonic acid plus epinephrine, and A23187 were used as agonists with CH platelets. In heterozygous CH dogs, platelet aggregation was intermediately defective when tested with collagen and PAF as agonists. Thromboxane B2 (TXB2) concentrations (mean +/- SD; pg/10(6) platelets), as measured by RIA, were similar in CH and normal dogs both prior to (CH: 7.6 +/- 7.0; N: 5.5 +/- 3.9) and after collagen stimulation (collagen: 141.3 +/- 42.5; 123.1 +/- 38.4). Granule storage pools of serotonin and platelet adenine nucleotides were markedly decreased in homozygous CH but not heterozygous CH dogs. Thrombin stimulated phosphorylation of 40- and 20-kd proteins in platelets from CH and normal dogs to an equal extent. However, collagen-stimulated phosphorylation of the 40- but not the 20-kd protein was significantly decreased in platelets from CH dogs. These data suggest that there is a biochemical defect in platelets from CH dogs that results in storage pool disease and decreased phosphorylation of a 40-kd protein. PMID- 1893970 TI - Platelet factor 4 gene expression in a human megakaryocytic leukemia cell line (CMK) and its differentiated subclone (CMK11-5). AB - The human cell line CMK spontaneously expresses megakaryocytic characteristics and can be induced to differentiate into mature megakaryocytes after exposure to 12-O-tetradecanoylphorbol-13-acetate (TPA). In comparison with CMK, we have examined the characteristics of a subclone, designated as CMK11-5, that is morphologically larger than the parent clone CMK and contains multinucleated giant cells. All CMK11-5 cells were positive for platelet peroxidase (PPO) activity, and some contained abundant alpha-granules and well-developed demarcation membranes. CMK cells had few demarcation membranes and alpha granules, and 10% of these cells were found not to possess PPO activity. Phenotypic analysis revealed the percentage of CMK11-5 cells for platelet glycoprotein (GP) IIb/IIIa (CD41a), and GPIIIa (CD61) was greater than that for CMK cells. On the basis of these findings, CMK11-5 cells were considered to be more differentiated than CMK cells. We further examined the expression of GPIIb and platelet factor 4 (PF4) mRNA by Northern blot hybridization using 32P-labeled cDNA probes for GPIIb and PF4 in CMK and CMK11-5 cells. CMK cells exhibited mRNA for GPIIb, and its expression was augmented by TPA addition, but not PF4. In contrast, CMK11-5 cells were found to contain mRNA for GPIIb and PF4, and their mRNA levels were increased by the addition of TPA. The immunoreactive PF4 antigen was not detected in the TPA-treated CMK11-5 cells or in the culture medium of these cells. These results indicate that expression of mRNA for PF4 is a useful marker for the identification of mature megakaryocytes. Detection of mRNA for PF4 is a more sensitive method for characterization of megakaryocytic cells than that for the PF4 antigen. PMID- 1893971 TI - Cooperative effects of hemin and anthracyclines in promoting terminal erythroid maturation in K562 human erythroleukemia cells. AB - Simultaneous exposure to 30 microM hemin and 3 x 10(-8) M aclacinomycin (ACL) or mussetamycin for 6 days led to terminal differentiation of K562 cells. The number of hemoglobinized cells and the total hemoglobin content of cells treated with both ACL and hemin exceeded the sum of the corresponding values induced in response to each of these two agents when used alone. Although neither ACL nor hemin alone induced substantial morphological maturation, 40%-45% of cells treated with both agents developed the morphological characteristics of orthochromatophilic normoblasts, a level of maturation not previously reported for this highly malignant cell line. Subcloning of K562 cells that had been treated with both ACL and hemin in inducer-free plasma clots revealed a 50% decrease in the clonogenic potential of these cells, even though the cells in the original cultures were still growing at only a moderately decreased rate. Despite the apparent terminal maturation of K562 cells induced with both ACL and hemin, with an advanced level of morphologic maturation and hemoglobin synthesis accompanied by a loss of proliferative capacity, these cells remained incapable of producing beta-globin chains and hence hemoglobin A. PMID- 1893972 TI - Differentiation of chimeric bone marrow in vivo reveals genotype-restricted contributions to hematopoiesis. AB - Bone marrow transplantation is of increasing utility in cancer treatment and is an important component of gene therapy protocols. Understanding the functional identities of progenitor cells involved in repopulation is important for the optimal application of this procedure. We have simultaneously used two types of genetic markers to study engraftment of mice after irradiation. The first involves intrinsic genetic differences, including a cellular marker, between two mouse strains used to construct chimeric mice by aggregating embryos. To produce a second marking system, bone marrow from these allophenic mice was subsequently infected with retrovirus. Individual progenitor cells, including primitive lympho hematopoietic stem cells, participating in repopulation were identified by virtue of their uniquely marked clonal progeny. In this way numbers and genotypic identities of clones contributing to repopulation were determined. Engraftment could be divided into two distinguishable temporal phases. The first comprised roughly the first 3-4 months following transplant and was characterized by numerous clones, many of which apparently had limited lineage potencies. The subsequent phase was characterized by few, often a single, clones represented in all lympho-hematopoietic tissues. These findings are consistent with the notion that different classes of progenitor cells are differentially responsible for temporal progression. More differentiated, perhaps lineage restricted, progenitors transiently dominate the first few months before the emergence of pluripotent stem cell clones. Senescence of progenitors of the first phase may reflect their limited lifespans. A clear genotypic difference was obvious in engraftment. Cells of one strain, DBA/2, completely dominated the first temporal phase, whereas the C57BL/6 partner strain dominated the second phase. The genotype-restricted dominance of different stages of repopulation suggests important differences in the organization and regulation of stem and progenitor cell populations. Inherent differences in seeding, proliferation, and differentiation of progenitors of the two inbred strains may account for the differences. This in vivo model of competitive repopulation provides the opportunity to explore potentially important loci in the process of engraftment. We propose that DBA/2 progenitor cells, due to a proliferative and/or numerical advantage, account for their superiority immediately after engraftment. C57BL/6 stem cells, with long-term repopulating potential, predominate later, perhaps because of subtle numerical or proliferative advantages. PMID- 1893973 TI - Short- and long-term repopulation of lethally irradiated mice by bone marrow stem cells enriched on the basis of light scatter and Hoechst 33342 fluorescence. AB - Murine bone marrow subpopulations enriched in hemopoietic stem cells were transfused into lethally irradiated hosts to determine the contribution of host cells and two types of donor cells to marrow repopulation. Donor cell suspensions were a mixture of marrows from two congenic lines of mice containing electrophoretically distinguishable alloenzymes of phosphoglycerate kinase (PGK-A and PGK-B). The donor cells were sorted by high forward light scatter, low-to intermediate perpendicular light scatter, and low Hoechst 33342 fluorescence intensity. The congenic hosts contained a third distinct marker, glucose phosphate isomerase (GPI-A). The two markers in the donor cells allowed determination of the clones generated by the seeded cells over a 36-week period of observation. The clone number declined rapidly during the first 12 weeks following transplantation and reached stable levels at 20 weeks, indicating the number of long-term repopulating cells (LTRC). The sorted subpopulation was enriched 170-fold for day-13 spleen colony-forming units (CFU-S), 235-fold for cells providing a 30-day survival, and 136- to 160-fold for LTRC. Survival for the 36-week observation period was 40%-100% for groups of hosts receiving 100 3000 sorted cells and 80% for controls receiving 2 x 10(5) unsorted cells. In all groups, similar distribution of phenotypes among peripheral blood erythrocytes, platelets, and lymphocytes at 36 weeks suggested that the repopulating donor stem cells were pluripotential. Transfusion of 3000 sorted cells, containing about 5 LTRC and 60 CFU-S, assured continuous repopulation with 95%-100% donor cells 4 to 36 weeks after transplantation, whereas significant numbers of host cells re emerged temporarily or permanently when lower numbers of LTRC and CFU-S were transfused. The data indicate that both the quality and quantity of pluripotential stem cells in sorted bone marrow are important for complete long term marrow reconstitution. PMID- 1893974 TI - Characterization of FDCP-2, a cloned hemopoietic progenitor cell deficient in homing protein. AB - The progenitor cell clone, FDCP-2, was found to lack the expression of membrane homing lectin that recognizes galactosyl and mannosyl residues of glycoconjugate on the surface of hemopoietic stroma. Adherence of these cells to hemopoietic stroma is significantly less than that of either normal clones B6SUt or FDCP-1, although their adherence to nonhemopoietic stroma 3T3 is preserved. As determined by electron microscopy, the cells lack microvilli, which in their normal counterparts serve to mediate the contact and adherence to hemopoietic stroma. This cell line can be useful as a negative control in elucidating the molecular basis of the homing phenomenon and its function in the regulation of hemopoiesis. PMID- 1893975 TI - Erythropoietin production: a personal view. PMID- 1893976 TI - Growth of primary human acute leukemia in severe combined immunodeficient mice. AB - Seven populations of human leukaemic cells were implanted i.v. into sublethally irradiated severe combined immunodeficient (scid) mice. Growth of leukaemia was monitored by labelling murine peripheral blood (PB) cells with an anti-HLA monoclonal antibody and flow cytometric analysis. Two of the populations transplanted were fresh acute lymphoblastic leukaemia (ALL) bone marrow (BM) cells which both caused sustained proliferative growth in scid mice. Human cells accounted for up to a mean of 87% of the total nucleated cells (TNC) in the PB of these mice between weeks 12-15. One of these populations was passaged into fresh mice and frank leukaemia was again established. Three populations of cryopreserved acute myeloblastic leukaemia (AML) cells (2 obtained from PB and 1 from BM) and one population of cryopreserved biphenotypic acute leukaemia BM cells, only grew to a maximum of 4% within the 15 week period of the experiment. A cell population from an AML cell line (HL60), however, did engraft and proliferate resulting in a rapid deterioration of these mice between weeks 3-6 when the proportion of human cells accounted for 9% of the TNC in the PB. PMID- 1893977 TI - Effects of rrSCF on multiple cytokine responsive HPP-CFC generated from SCA+Lin- murine hematopoietic progenitors. AB - We have previously defined a subset of High Proliferative Potential Colony Forming Cells (HPP-CFC), derived from murine marrow purified for early progenitors expressing the Stem Cell Antigen (SCA+) and lacking terminal lineage markers (Lin-), which are responsive to multiple cytokines in combination. Stem Cell Factor (SCF), a multipotent growth factor which is the ligand for c-kit, synergizes with these multiple factor combinations to increase colony number and size. SCF is thus a potent mitogen with direct action on early hematopoietic progenitor cells. These data are consistent with a model of stromal control of hematopoiesis via elaboration of multiple cytokines in locally high concentration, with SCF playing a central role. PMID- 1893978 TI - Functionally complex muscles of the cat hindlimb. I. Patterns of activation across sartorius. AB - The cat sartorius (SA) can be divided functionally into an anterior (SAa), knee extensor portion and a medial (SAm), knee flexor portion; it can be further subdivided anatomically by multiple nerve branches into parallel longitudinal columns that terminate in a distributed insertion at the knee with a continuous range of moment arms. Thus, SA may be controlled by a discrete number of motoneuron task groups reflecting a small number of central command signals or by a continuum of activation patterns associated with a continuum of moment arms. To resolve this question, the activation patterns across the width of the SA were recorded with an electrode array during three kinematically different movements- treadmill locomotion, scratching and paw shaking, in awake, unrestrained cats. Uniformity of activation along the longitudinal axis was also examined because individual muscle fibers do not extend the length of the SA. In addition, the cutaneous reflex responses were recorded throughout all regions of the SA during locomotion. Two fascial surface-patch arrays, each carrying 4-8 pairs of bipolar EMG electrodes, were sutured to the inner surface of the SA, one placed proximally and the other more distally. Each array sampled separate sites across the anterior to medial axis of SA. During locomotion, two basic EMG patterns were observed: the two burst-per-step-cycle pattern typical of SAa and the single burst pattern typical of SAm. There was an abrupt transition in the pattern of activation recorded in the two parts of SA during locomotion, and no continuum in the activation pattern was observed. Stimulation of both sural and saphenous cutaneous nerves during locomotion produced reflex responses that were uniformly distributed throughout SA, in contrast to the regional differences noted during unperturbed walking. Similarly, during scratching and paw shaking all parts of the SA were active simultaneously but with regional differences in EMG amplitude. The abrupt functional border between SAa and SAm coincided with the division of the SA into a knee flexor vs. a knee extensor. In all cases, the quantitative and qualitative differences in SAa and SAm EMGs were uniformly recorded throughout the entire extent of SAa or SAm; i.e., there was no segregation of activity within either SAa or SAm. Furthermore, the time course of EMG from each proximal recording site was nearly identical to the corresponding distal site, indicating no segregation of function along the longitudinal axis of SA. These results indicate that SAa and SAm constitute the smallest functional modules that can be recruited in SA.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1893979 TI - Functionally complex muscles of the cat hindlimb. II. Mechanical and architectural heterogenity within the biceps femoris. AB - The goal of this study was to analyze the architecture of the cat biceps femoris (BF), a multifunctional hamstring muscle, and to evaluate the relationships between muscle architecture, limb position, and muscle function during natural movement. The BF muscle consists of three neuromuscular compartments: anterior (BFa), middle (BFm) and posterior (BFp). Each compartment is innervated by a separate nerve branch. Nerve branch stimulation and 2-dimensional surface EMG recordings showed that individual compartment territories were discrete and non overlapping with well-defined borders. Comparisons of the three compartments revealed consistent differences in architecture, relationship to the skeleton, and function. The BFa crossed only the hip joint and appears to function as a pure hip extensor. The BFm had equal lever arm lengths to the hip and knee joints, appears to function as a hip extensor, and may contribute to knee flexion or femoral rotation. The BFp had a greater lever arm to the knee, functions as a knee flexor, and may contribute to hip extension, femoral rotation or ankle extension. Measurements of individual fascicles from the three compartments revealed a surprising range of lengths, 3.3-12.0 cm. Microdissection of gold stained tissue showed that fascicles from all compartments were comprised of interdigitated, short fibers (range: 0.6-5.0 cm; average 2.14 cm) arranged in series in fascicles, running parallel to the origin-insertion axis of each muscle compartment. In regions of fiber interdigitation, the fiber endings were round and tapered (taper lengths: 1-11 mm) although flat, tapering endings like ribbons were occasionally found. As hip and knee joint angles were varied over physiological ranges corresponding to minimal to maximal muscle length, fascicles of the three compartments changed length disproportionately. Long BFa fascicles maximally lengthened 10-18%, consistent with in vivo length measures during treadmill locomotion. However, the long BFp fascicles lengthened 25-45%, and the relatively short fascicles near the BFm/BFp border maximally lengthened 45-53%. How do these unexpectedly large length changes affect sarcomere lengths? Using laser diffraction to measure sarcomeres, static fascicle and sarcomere lengths were compared in muscles that went into rigor mortis after fixing the hip and knee joint angles. Sarcomeres within the short BFm/BFp and long BFp fascicles consistently lengthened proportionately less than the whole fascicle. It remains to be determined how and where the fascicle length changes are dissipated in the connective tissue between the interdigitated muscle fibers and whether such a series-compliance operates during the large excursions over which this muscle normally works. PMID- 1893980 TI - Functionally complex muscles of the cat hindlimb. III. Differential activation within biceps femoris during postural perturbations. AB - The biceps femoris (BF) muscle is divided into three neuromuscular compartments defined by the innervation patterns of the main nerve branches (English and Weeks 1987). The goals of this study were i) to determine how different regions of the biceps femoris muscle are activated in the intact cat during a broad range of limb movements evoked by perturbations of stance posture, and ii) to determine the relationship between the anatomical compartments of biceps femoris and the functional units as defined in this task. Cats were trained to stand on a moveable platform with each paw on a triaxial force plate. The animal's stance was perturbed by linear translation of the platform in each of sixteen different directions in the horizontal plane. EMG activity was recorded from eight sites across the width of the left biceps femoris muscle. During quiet stance only the anterior compartment was tonically active, presumably contributing to hip extensor torque in the maintenance of stance. During platform translation, evoked EMG activity was recorded from each electrode pair for a wide range of directions of perturbation; as direction changed progressively, the amplitude of evoked activity from any electrode pair increased to a maximum and then decreased. When the EMG amplitude was plotted in polar coordinates as a function of translation direction, the region of response formed a petal shaped area in the horizontal plane, termed the EMG tuning curve. The compartments of the BF muscle were not activated homogeneously. The tuning curve of the anterior BF compartment was similar to that of other hip extensors, and coincided with the region of postero lateral force production by the hindlimb against the support. The tuning curve of the middle BF compartment was shifted in a counterclockwise direction from that of the anterior compartment, but overlapped extensively with it; the middle BF tuning curve was similar to that of anterior gracilis. The tuning curve of the posterior biceps compartment was rotated further counterclockwise and overlapped very little with that of the middle BF compartment. The posterior BF was activated in a pattern similar to that of other knee flexors. The functional units of BF activation were not identical with the neuromuscular compartments defined by the main nerve branches. As direction of the perturbation changed, the region of BF that was activated moved progressively across the muscle. This progression of the active region was continuous across BFa and BFm, whereas there was a jump, or discontinuity at the border between BFm and BFp.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1893981 TI - Functionally complex muscles of the cat hindlimb. IV. Intramuscular distribution of movement command signals and cutaneous reflexes in broad, bifunctional thigh muscles. AB - Similarities between the muscle synergies associated with the flexion reflex and locomotion in reduced preparations have suggested that spinal circuits subserving these two motor tasks might share common interneurons. To test this hypothesis in functionally complex muscles, we studied the interaction between low-threshold cutaneous afferents and the locomotor central pattern generator (CPG) during treadmill locomotion in awake, intact cats. Electrical stimuli were delivered via implanted nerve cuff electrodes at all phases of locomotion, and EMGs were recorded from fourteen intramuscular subregions in eight bifunctional thigh muscles (adductor femoris, biceps femoris, caudofemoralis, gracilis, semimembranosus, semitendinosus, tensor fasciae latae, and tenuissimus). In addition, the EMG patterns recorded during locomotion were compared with those recorded during two other centrally driven rhythmical behaviors, scratching and paw shaking, to determine whether the functional relationships among these intramuscular subregions were fixed or task dependent. Four of the five broad, bifunctional muscles studied (biceps femoris, gracilis, semimembranosus, and tensor fasciae latae) had functional subunits that could be differentially activated in one or more of the three movements studied; adductor femoris was consistently uniformly activated despite its distributed skeletal attachments. The pattern of recruitment of the intramuscular functional subunits was movement specific. The locomotor CPG and cutaneous reflex pathways both similarly subdivided some bifunctional muscles, but not others, into intramuscular subregions. The results of the present study confirm that some combinations of muscle subregions and cutaneous nerves constitute simple reciprocal categories of flexors and extensors, as described originally by Sherrington (1910). "Typical" low threshold excitatory or inhibitory reflex responses were produced in muscles or muscle subregions that were recruited as "net" flexors of extensors, respectively. However, muscles with complex activation patterns during walking often had very individualized, complex reflex responses during locomotion that did not conform to the background locomotion synergies. All of the reflex responses observed were mediated by low threshold cutaneous afferents. These data indicate that there are multiple, low threshold, excitatory and inhibitory cutaneous reflex pathways that have highly specialized connections with flexor and extensor muscles and even their intramuscular subregions. It is also clear that the premotoneuronal circuits mediating these cutaneous reflex effects are not necessarily synonymous with those of the locomotor CPG. These two systems do interact powerfully, however, suggesting some convergence. The nature of the convergence between the CPG and the many independent subsets of spinal interneurons mediating cutaneous reflexes is specialized and muscle subregion specific. PMID- 1893982 TI - Scaling of the metrics of visually-guided arm movements during motor learning in primates. AB - Hand trajectory, tangential velocity and acceleration, time and distance until peak velocity and reaction time were analyzed during the process of learning a skilled, visually-guided arm movement. Primates were trained to move a cursor with a manipulandum from a start box to target boxes displayed on a horizontal video screen during control conditions and when the relationship (gain) between the cursor and manipulandum was altered. The animals adapted to the altered feedback over 100-200 trials. A subsequent testing phase with randomly interspersed trials using the control gain demonstrated that the animals had modified their movements appropriately for the novel gain. Examination of the kinematics revealed that in adapting to a novel gain, primates scaled movement amplitude, tangential velocity, acceleration, and duration appropriately for the distance the hand needed to travel. Yet time to peak velocity was kept constant. Reaction time also remained unchanged for three of the four animals. Movements were performed in two phases, the first from movement onset to peak velocity and the second from peak velocity until the end of the movement. During the first phase the shape of the trajectory and velocity profile were stereotypic and without evidence of any corrections, consistent with this phase being essentially open loop. However, corrections occurred in the second phase and we propose visual feedback was used to correct for the difference in hand/cursor position. Learning appeared to involve utilizing the errors from previous trials to modify the early feedforward phase of subsequent trials. Peak tangential velocity, total movement duration and distance reached at peak tangential velocity all scaled linearly with the total movement distance required at each gain. Based on regression analyses, for none of these variables were the changes in learning completely adequate to compensate for total distance required. However, distance to peak velocity scaled with peak velocity in relation to the control gain. The results show that non-human primates adopt a consistent strategy when learning to scale a multi-joint movement. The metrics of the movement scaled yet the time to peak velocity remained constant, suggesting independent control of time and amplitude. Keeping time to peak velocity constant as well as the scaling of peak velocity with distance to peak velocity are viewed as ways to simplify the learning process. PMID- 1893983 TI - Grafting of fetal substantia nigra to striatum reverses behavioral deficits induced by MPTP in primates: a comparison with other types of grafts as controls. AB - Fetal substantia nigra (SN) cells were transplanted into the caudate nucleus (CN) of four vervet monkeys (Cercopithecus aethiops sabaeus) that had been treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). MPTP treatment appears to produce a syndrome similar to that observed in patients with idiopathic Parkinson's disease. Normal and parkinsonian behaviors were quantitated by trained observers 5 days/week. Twenty-eight behaviors based on previous factor analyses were individually scored and rated. Parkinsonian signs included freezing, head and limb tremor, difficulty in eating, delayed initiation of movement, poverty of movement, tremor that stopped with intention, decreased response to threats, and lying immobile in the cage. These signs were combined to give an overall rating of parkinsonism. A summary measure of 'normal' healthy behavior was also examined, including such behaviors as yawning, scratching, self grooming, shifting, and eating. Overall ratings of parkinsonism increased and those of healthy behavior decreased after MPTP. In the 4 monkeys grafted with fetal SN cells into the CN, behavior returned to pre-treatment levels by the time of sacrifice (2, 5, or 7.5 months after grafting). Three control subjects were transplanted with either SN cells into an inappropriate brain site (cortex) or inappropriate, non-dopaminergic, cells (cerebellar) into the CN. Subjects were also compared with three control animals that did not receive MPTP but received cryopreserved or fresh SN and other cells into the CN. Only MPTP-treated subjects that received SN cells into the CN showed evidence of a reversal of the MPTP syndrome after transplantation. In addition, grafting in animals that were not MPTP-treated did not appear to affect behavior. This paper reports the specific behavioral effects of severe MPTP toxicity that were or were not reversed after transplantation and suggests that only fetal SN cells grafted into the CN may be able to reverse behavioral deficits in MPTP-treated monkeys. PMID- 1893984 TI - Paraventricular nucleus magnocellular neuronal responses following electrical stimulation of the midbrain dorsal raphe. AB - In order to determine the responses of paraventricular nucleus magnocellular neurones following activation of central serotonergic pathways, single unit activity was recorded and responses following electrical stimulation of the midbrain dorsal raphe nucleus were examined. Approximately one third (32%) of the phasically active, vasopressin-secreting neurones were inhibited by the stimulation, the remaining such cells being nonresponsive. In contrast, only two of the non-phasic cells (13%) were inhibited by the stimulation whilst 53% were excited (p less than 0.005, chi2-test). The onset latency of both inhibitory and excitatory responses were similar, whilst offset of the inhibitory responses was about twice that of the excitatory responses (p less than 0.005, t-test). Two of the non-phasic cells were antidromically identified as projecting to the dorsal raphe. The results obtained indicate a role for dorsal raphe projections to the paraventricular nucleus in the regulation of neurohypophysial hormone secretion. The observation that different sub-populations of the cells recorded showed different responses, suggests that several mechanisms may be involved in the control of neuronal activity in the region recorded, in response to activation of the central serotonergic pathway examined. The results obtained are intended to further clarify the neural mechanisms regulating the secretion of vasopressin and oxytocin from the neurohypophysis. PMID- 1893985 TI - Bilateral labyrinthectomy in the cat: motor behaviour and quiet stance parameters. AB - The purpose of this study was to examine the effect of bilateral labyrinthectomy on quiet stance in the freely-standing cat. Since loss of the vestibular end organs produces marked deficits in motor behaviour, including ataxia and problems with balance, we hypothesized that labyrinthectomized animals would show impairment in quantitative measures of stance. Stance was quantified in terms of the ground reaction forces under each limb and the tonic electromyographic (EMG) activity of selected muscles. Animals were labyrinthectomized by drilling into the vestibule and removing the vestibular epithelium. Following lesion, animals were able to stand unsupported on the force platform within 2 days. To our surprise, the lesioned animals showed little change in stance parameters from the control, pre-lesion state. Thus, our hypothesis of changes in stance parameters was not supported. There was no change in the distribution of vertical forces under the limbs and no increase in sway, as measured by the area of excursion of the centre of pressure over time. The horizontal plane forces, which were diagonally directed prior to lesion, became more laterally directed and larger in amplitude. The change in direction persisted even after the animals had fully compensated for the lesion, but the force amplitudes returned to control values within 10-12 days. The change in horizontal force direction was similar to that observed in normal animals that were required to stand with their paws closer than preferred in the sagittal plane (unpublished observations). EMG activity changed in some muscles but not others, and usually transiently.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1893987 TI - Human perception of horizontal trunk and head rotation in space during vestibular and neck stimulation. AB - The vestibular signal of head motion in space must be complemented by a neck signal of the trunk-to-head excursion in order to provide the individual with information on trunk motion in space. This consideration led us to study psychophysically the role of vestibular-neck interaction for human self-motion perception. Subjects (Ss) were presented with passive horizontal rotations of their trunk and/or head (sinusoidal rotations, f = 0.025 - 0.4 Hz) in the dark for vestibular and neck stimulation, as well as for combinations of both. Ss' perception was evaluated in terms of gain (veridical perception of stimulus magnitude, G = 1), phase, and detection threshold. (1) Perception of trunk rotation in space. During vestibular stimulation (whole-body rotation) and neck stimulation (trunk rotation with the head kept stationary) the frequency-transfer characteristics underlying this perception were very similar. The gain fell short; it was only about 0.7 at 0.4 and 0.2 Hz stimulus frequency and was further attenuated with decreasing frequency. In contrast, the phase was close to that of actual trunk position. The gain attenuation was found to be a function of the peak angular velocity of the stimulus, a fact, which we related to a 'velocity threshold' of the order of 1 deg/s. During the various vestibular-neck combinations used, Ss' perception was again erroneous, reflecting essentially the sum of its two non-ideal constituents. However, there was one noticeable exception; during the combination 'head rotation on stationary trunk', Ss veridically perceived their trunk as stationary (compatible with the notion that the sum yielded 'zero'). (2) Perception of head rotation in space. During vestibular stimulation, Ss' estimates showed the same non-ideal gain-vs. frequency characteristics as described above for the trunk. Neck stimulation induced an illusion as if the head had been rotated in space. This neck contribution was such that, when it was combined with its vestibular counterpart during head rotation on stationary trunk, the perception became almost veridical. On closer inspection, however, this neck contribution was found to reflect the sum of two components; one was the non-ideal neck signal contributing to the perception of 'trunk in space', the other was an almost ideal neck signal of head on-trunk rotation. (3) The results could be described by a simple model. In this model, the erroneous vestibular signal 'head in space' is primarily used to create an internal representation of 'trunk in space'.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1893986 TI - Task-related coding of stimulus and response in cat red nucleus. AB - In the present study we recorded the activity of single neurons in the forelimb area of red nucleus (RN) during performance of three step-tracking tasks designed to dissociate the coding of stimulus and response variables in the discharge of recorded neurons. In two of these tasks, the standard and stimulus-reversal arm tasks, elbow flexion and extension were elicited by different stimuli enabling us to distinguish activity correlated with the forelimb response from the stimulus eliciting it. The third task (neck task) allowed us to determine whether neuronal modulation was related to an unconditioned orienting response that occurred concurrently with the forelimb response. We have previously reported that these three tasks separate neurons in MCx whose modulation precedes the response (lead cells) into three distinct classes in which task-related activity either is correlated with the direction of the forelimb response, correlated with the stimulus, or not correlated with either (Martin and Ghez 1985). All lead cells, however, remained timed to the stimulus rather than to the response. The present results show that RN lead cells can be subdivided into the same three classes as those in MCx and their discharge was also contingent on the subsequent production of a behavioral response. (1) Force-direction neurons (35%; n = 16) showed changes in activity correlated with the production of forearm force in a particular direction suggesting that they could participate in selecting the appropriate forelimb response. The onset of task-related modulation of activity was better timed to the response, in contrast to force-direction neurons in MCx, which were better timed to the stimulus. (2) Stimulus-direction neurons (18%; n = 8) modulated their activity in relation to a particular stimulus evoking either flexor or extensor responses and during neck task performance. These neurons could be involved in processing stimulus information or in the production of neck torque. The task-related discharge of these lead cells was better timed to the stimulus than to either the forelimb or the neck response. (3) Nondirectional neurons (47%; n = 21) modulated their activity during all tasks examined. Their discharge did not correlate with any specific feature of the stimulus or response, and as a group, was better timed to the stimulus than to the response. Nondirectional neurons may participate in some aspect of motor preparation.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1893988 TI - Is there a preferred coordinate system for perception of hand orientation in three-dimensional space? AB - The purpose of this experiment was to determine the preferred coordinate system for representation of hand orientation in 3-dimensional space. The ability of human subjects to perceive angles of the hand in 3-dimensional space (elevation, yaw, roll angles-extrinsic coordinate system) was compared to their ability to perceive hand angles relative to the proximal upper limb segments (wrist joint angles, forearm pronation-intrinsic coordinate system). With eyes closed, subjects performed a matching task in which the experimenter positioned the left arm, forearm and hand and the right arm and forearm. Subjects were then told to match an angle in one of the two coordinate systems by moving only the right hand at the wrist or the forearm as in pronation or roll matching. Absolute constant error (ACE), variable error (VE) and normalized variable error (NVE-normalized to tested range of motion) of matching were quantified for each subject for each of the six angles matched. It was hypothesized that matching angles in a preferred coordinate system would be associated with lower ACE, VE and NVE. Overall, ACE and VE were lower for matching hand angles in the intrinsic coordinate system. This suggests that the preferred coordinate system involved specification of hand angles relative to forearm and arm angles (joint angles) rather than the hand angles relative to axes external to the upper limb. However, matching of pronation angles was associated with larger VE and NVE than roll angle matching. There were no significant differences in ACE between pronation and roll matching. In a second experiment subjects with their forearms constrained at different elevations matched hand elevation and wrist flexion angles. Thus, errors in matching the angles in the non-preferred coordinate system were predictable if the subjects were biased toward matching angles in the preferred coordinate system. Trends in the data suggested that subjects preferred matching hand elevation angles but these trends were not consistent within or between subjects. Thus a preferred intrinsic coordinate system for wrist flexion matching was not observed in this experiment. We suggest that matching angles when proximal limb segments are constrained is a simpler task for the subjects (VE lower than in the first experiment) and may bias the matching toward the extrinsic coordinate system. Thus, hand orientation in 3-dimensional space may be perceived as follows: wrist flexion and abduction angles together with forearm elevation and yaw are used to specify hand elevation and yaw; these together with hand roll angle, completely specify the hand angle in 3-dimensional space. PMID- 1893989 TI - Changes of slow cortical negative DC-potentials during the acquisition of a complex finger motor task. AB - To study whether electrophysiological correlates of increasing motor skill can be demonstrated in man, we recorded cortical negative DC-potentials during the acquisition of a complex finger movement in 21 subjects. The movement consisted in moving a matchstick to and fro between the index finger (II) and the little finger (V). Cortical negative DC-potentials were recorded at Fz, Cz, C1, C2 and Pz. As a control a simple finger movement was performed during the same session by 7 of the Ss. Both tasks were repeated 60-80 times and averages of the first and the last 15 artifact-free single runs were compared. Whereas only a slight, inconstant decrease in surface electronegativity during the simple motor task was observed, a significant reduction in potential size occurred during the complex task at Cz (maximum), C1, C2 and Pz but not at Fz. In addition, a significant difference in the decrease of surface electronegativity between various electrode positions was observed. We suggest that these changes in potential size during the process of motor learning may reflect an altered cortical organisation of movement control during the acquisition of a complex motor task. PMID- 1893990 TI - Eye and neck proprioceptive messages contribute to the spatial coding of retinal input in visually oriented activities. AB - The egocentric localization of objects in extrapersonal space requires that the retinal and extraretinal signals specifying the gaze direction be simultaneously processed. The question as to whether the extraretinal signal is of central or peripheral origin is still a matter of controversy, however. Three experiments were carried out to investigate the following hypotheses: 1) that the proprioceptive feedback originating in eye and neck muscles might provide the CNS with some indication about the gaze direction; and 2) that the retinal and proprioceptive extraretinal inputs might be jointly processed depending on whether they are of monocular or binocular origin. Application of low amplitude mechanical vibrations to either the extraocular or neck muscles (or both) of a subject looking monocularly at a small luminous target in darkness resulted in an illusory movement of the target, the direction of which depended on which muscle was stimulated. A slow upward target displacement occurred on vibrating the eye inferior rectus or the neck sterno-cleido-mastoidus muscles, whereas a downward shift was induced when the dorsal neck muscles (trapezius and splenius) were vibrated. The extent of the perceptual effects reported by subjects was measured in an open-loop pointing task in which they were asked to point at the perceived position of the target. These results extend to visually-oriented behavior the role of extraocular and neck proprioceptive inputs previously described in the case of postural regulation, since they clearly show that these messages contribute to specifying the gaze direction. This suggests that the extraretinal signal might include a proprioceptive component.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1893991 TI - Order parameters for the neural organization of single, multijoint limb movement patterns. AB - Subjects performed two patterns of coordination between the elbow and wrist joints of the right arm: 1) wrist flexion synchronized with elbow flexion and wrist extension with elbow extension (homologous muscle groups); and 2) wrist extension synchronized with elbow flexion and wrist flexion with elbow extension (nonhomologous muscle groups). As a parameter, cycling frequency, was increased, an abrupt switch in the phase relation between the elbow and wrist joints occurred. Similar effects were observed in underlying neuromuscular (EMG) timing patterns. Observed transitions depended on whether the forearm was prone or supine, not simply on the muscle pairing across the joints. With the forearm supine, transitions were from pattern (2) to pattern (1) above, and with the forearm prone the transitions were from pattern (1) to pattern (2). When subjects were initially prepared in pattern (1) with the forearm supine or in pattern (2) with the forearm prone, switching did not occur. En route to transitions, enhanced fluctuations in the phase relation occurred, indicating that loss of stability is at the origin of pattern change. Accompanying such changes in coordination were characteristic effects on end effector trajectories and velocity profiles. Possible neurophysiological mechanisms for context dependence in multijoint coordination are discussed. PMID- 1893992 TI - Human cyclovergence as a function of stimulus frequency and amplitude. AB - By the use of scleral search coils a continuous record of human cyclovergence was obtained while two identical 80 degrees textured patterns, presented dichoptically, oscillated in the frontal plane in counterphase through 1, 3 and 6 degrees of cyclorotation at frequencies between 0.05 and 2 Hz. The amplitude and gain of the response decreased exponentially with increasing stimulus frequency. As stimulus amplitude increased, response amplitude also increased but gain was highest for low-amplitude cyclorotations. For an amplitude of 1 degrees and a frequency of 0.05 Hz the gain reached 0.87 for two subjects. The phase lag increased from a few degrees at a frequency of 0.05 Hz to over 100 degrees at a frequency of 2 Hz. These results suggest that cyclovergence is designed to correct for small, slow drifts in the stereoscopic alignment of the images in the two eyes. Although the disparity in the textured display was not interpreted as slant, it provided a strong stimulus for cyclovergence. The cyclovergence caused a transfer of cyclodisparity into a superimposed vertical line, which was then perceived as slanting in depth. PMID- 1893993 TI - Development of human precision grip. I: Basic coordination of force. AB - The coordination of manipulative forces was examined while children and adults repeatedly lifted a small object between the thumb and index finger. Grip force, load force (vertical lifting force), grip force rate and the vertical position of the test object were continuously measured. In adults, the force generation was highly automatized and was nearly invariant between trials. After a preload phase in which the grip was established, the grip and load forces increased in parallel under isometric conditions until the load force overcame the force of gravity and the object started to move. During this loading phase, the force rate profiles were essentially bell shaped and single peaked, suggesting that the force increases were programmed as one coordinated event. Children below the age of two exhibited a prolonged preload phase and a loading phase during which the grip and load forces did not increase in parallel. A major increase in grip force preceded the increase in load force, and at the start of the loading phase, the grip force was usually several Newtons (N). The force rate profiles were multi peaked with stepwise force increases most likely allowing peripheral feedback to play an important role in the control of the forces. After the age of two, the grip force increased less during the preload phase. The loading phase was more regularly characterized by a parallel increase of the grip force and load force and the duration of the various phases decreased. The older children programmed the forces in one force rate pulse indicating the emergence of an anticipatory strategy. Yet, the mature coordination of forces was not fully developed until several years later.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1893995 TI - Endothelium-derived relaxing factor is a nitrosyl iron complex with thiol ligands. AB - A hypothesis is put forward on the nature of the endothelium-derived relaxing factor (EDRF) which is released from vascular endothelial cells by acetylcholine, bradykinin and other agonists. It is suggested that EDRF is a nitrosyl iron complex with low-molecular thiol ligands, most probably with cysteine. Its active principle is nitric oxide (NO). This free radical is stabilized by inclusion into the iron complex, which promotes NO transfer within the cell and between cells. Subsequent release of NO from these complexes results from thiol group oxidation. PMID- 1893994 TI - Interlimb reflexes following cervical spinal cord injury in man. AB - The reflex interconnection of lower and upper extremity muscles was investigated in subjects with chronic (greater than 1 year post-injury) lesions to the cervical spinal cord. Lower extremity mixed nerves were stimulated with single shocks or with brief trains of high-frequency stimuli of varying intensities. EMG from a number of lower and upper extremity muscles was recorded on magnetic tape for later analysis. In one population of spinal cord injury (SCI) subjects, single stimuli to lower extremity nerves resulted in muscle responses in both ipsi- and contralateral upper extremity muscles. The minimal response latency to a single shock was typically much less in muscles on the ipsilateral side than for contralateral upper extremity muscles. Application of brief trains of stimuli (for example, 2 stimulus pulses at 500 Hz) typically resulted in a large reduction in latency to the contralateral motor response, such that it was now approximately equal to the ipsilateral motor response latency. This decline in response latency was not gradual with increasing afferent input. Instead, the response occurred either early or late, but not at intermediate latencies. Stimuli which were subthreshold for evoking M-waves or H-reflexes were sometimes still adequate to evoke upper extremity motor responses. Once the threshold had been exceeded, the magnitude of the evoked response appeared to be independent of the stimulus magnitude. These reflex interconnections of lower and upper extremities were obtained only from subjects with chronic and motor-complete cervical spinal cord injury. No such interlimb responses were seen in control subjects, or in subjects who had recovered some motor function below the level of their injury, and were now considered to be motor-incomplete quadriplegics. PMID- 1893996 TI - Legume lectins interact with muramic acid and N-acetylmuramic acid. AB - The inhibitory potency of both muramic acid (MurAc) and N-acetylmuramic acid (MurNAc) on various legume lectins, including Glc/Man- and Gal/GalNAc-specific lectins, was investigated by a haemagglutination inhibition technique. Data indicated that many lectins, especially those specific for Glc/Man, specifically interact with MurAc and MurNAc often to a greater extent than with other monosaccharides and their derivatives, such as N-acetylglucosamine (GlcNAc) and sialic acid. Glc/Man-specific lectins were also shown to interact with the muramyl-dipeptide MurNAc-D-Ala-D-isoGln. These interactions could explain why various lectins readily agglutinate some bacterial strains of which cell walls contain peptidoglycans with high amounts of MurNAc. PMID- 1893997 TI - cDNA sequence and differential expression of the mouse Ca2+/calmodulin-dependent protein kinase IV gene. AB - We have isolated and sequenced a mouse brain cDNA encoding Ca2+/calmodulin dependent protein kinase IV. The sequence predicts an acidic protein (pI = 4.56) of 469 amino acids (Mr = 52,627) that contains kinase catalytic and calmodulin binding domains. The carboxy region has several primary structural features that suggest it may be a readily cleaved attachment domain. This region is highly charged and hydrophilic and contains several PEST sequences, motifs associated with high turnover proteins. Of the tissues examined, expression of the CaM kinase IV gene is restricted to brain and testis, where transcripts are differentially expressed to produce a kinase in both tissues and a calmodulin binding protein, calspermin, in testis that lacks a kinase catalytic domain. PMID- 1893998 TI - Different expression time of the 105-kDa protein and 90-kDa heat-shock protein in rat testis. AB - To understand the physiological functions of the 105-kDa protein which is testis specific and HSP90 (90-kDa heat-shock protein) related protein, the appearance of it in the testis has been followed during the development of rat. On immunoblotting analysis, the 105-kDa protein did not appear until after the age of five weeks, while HSP90 could be detected at three weeks. In the spermatozoa, the 105-kDa protein was much abundant but not in the LC-540 cells (a cell line from Leydig cell tumor in rat testis) cytosol. This finding has attracted much attention to the relationship between this protein and sperm functions. PMID- 1893999 TI - Metaphase-specific phosphorylations weaken the association between chromosomal proteins HMG 14 and 17, and DNA. AB - The high-mobility-group proteins HMG 14 and 17 have been isolated from human cells arrested in metaphase. The affinity between an unphosphorylated and two phosphorylated forms of these proteins, and DNA has been investigated using columns of single-stranded and double-stranded DNA. It was shown that the most phosphorylated forms had much lower affinity for single-stranded and double stranded DNA compared to the unphosphorylated form present in interphase cells. The results are in accordance with the view that HMG 14 and 17 may dissociate transiently from chromatin during mitosis. PMID- 1894000 TI - Two types of linkage between codon usage and gene-expression levels. AB - The relation between codon usage and gene-expression levels is an intensively investigated and discussed topic in the field of molecular evolution. We statistically analyzed 25 Escherichia coli gene sequences by a new classification of synonymous codons and found that (i) there are two distinct types of linkage between codon usage and gene-expression levels in E. coli, and (ii) one of the two kinds of codon preferences (the codon preference concerned with interaction of GC/AT choice at three codon positions) is observed significantly in weakly expressed genes. PMID- 1894001 TI - The complete amino acid sequence of ribonuclease from the seeds of bitter gourd (Momordica charantia). PMID- 1894003 TI - Membrane fusion during infection of Escherichia coli cells by phage T4. AB - Phage T4 infection of Escherichia coli was studied by thin-section and freeze fracture electron microscopy. It was found that phage T4 induces the formation of a bridge between the outer and inner membranes of E. coli. A membrane fusion during the infection is suggested. PMID- 1894002 TI - Lethal neurotoxicity in mice of the basic domains of HIV and SIV Rev proteins. Study of these regions by circular dichroism. AB - We have recently reported a basic domain-mediated neurotoxic activity of HIV-1 Tat [1991, J. Virol. 65, 961-965]. Here we have tested the neurotoxicity in vivo of several Rev-related synthetic peptides and found that only those mimicking the basic regions of Rev from HIV-1, HIV-2 and SIV were lethal to mice. In contrast, the homologous domain of HTLV-1 Rex was found to be inactive for lethal activity. Analysis of the tropism of these peptides for phospholipids has demonstrated a direct interaction of the basic domain-containing peptides, except Rex, with acidic--but not neutral--phospholipids. As determined by circular dichroism, a possible correlation between the conformation of the basic regions and the toxicity is discussed. PMID- 1894004 TI - Influence of the H-subunit and Fe2+ on electron transport from I- to QA in Fe(2+) free and/or H-free reaction centers from Rhodobacter sphaeroides R-26. AB - From reaction centres (RC) of Rhodobacter sphaeroides R-26 two LM preparations with 0.90 Fe2+/RC (LM) and 0.10 Fe2+/RC (LM/dFe) were prepared. Reconstitution of LM/dFe with the H-subunit and subsequently with Zn2+ yielded LMH/dFe and LMH/dFe and LMH/dFe + Zn preparations, respectively. In these four samples the decay of the primary radical pair P+I- was studied by means of transient absorption spectroscopy and compared with that in native RC. In LMH/dFe the reduction of QA by Bpheo a occurred in 5 ns, with concomitant increase in the yield of PT, the triplet state of the primary donor. In the LM/dFe, LM and LMH/dFe + Zn preparations the decay of I- had the same rate (200 ps)-1 as in native RC. Thus, neither the H-subunit in the RC nor a divalent metal as Fe2+ or Zn2+ are necessary per se for fast reduction of QA. Only demetallation in the presence of the H-subunit slows down the reduction of QA. PMID- 1894005 TI - The origin of matrix metalloproteinases and their familial relationships. AB - New computer comparisons of the sequences of mammalian matrix metalloproteinases have established for the first time strong links with bacterial metalloproteinases. We also propose that there are five groups in the family of matrix metalloproteinases, although only three are as yet well-characterized as proteins, and discuss their origin and relationships with other zinc containing proteases. PMID- 1894007 TI - Effects of human low-density lipoproteins on the nucleotide patterns of cultured pig aortic endothelial cells. AB - Cultured pig aortic endothelial cells display significant changes in their nucleotide patterns after incubation with LDL-cholesterol purified from normal human plasma as determined by HPLC. Incubation at 70 mg/dl LDL-cholesterol for 24 h at 37 degrees C caused a significant decrease (P less than 0.001) in ATP from a control value of 14.0 +/- 0.4 nmol/mg protein to 6.6 +/- 0.9 nmol/mg protein (n = 4) with a concomitant increase in ADP and AMP. At higher LDL concentrations these effects were even more pronounced but still reversible. Akin to adenine nucleotides, the guanosine and uridine phosphates as determined by HPLC were changed. In contrast to LDL, HDL and VLDL were ineffectual. PMID- 1894006 TI - Purification and characterization of N-acyl-D-glutamate deacylase from Alcaligenes xylosoxydans subsp. xylosoxydans A-6. AB - The purification and properties of N-acyl-D-glutamate deacylase from the cell extracts of Alcaligenes xylosoxydans subsp. xylosoxydans A-6 were studied. The two active fractions (peaks I and II) were obtained by a Mono Q column chromatography. The predominant enzyme (peak I) has been purified, 1960-fold to homogeneity and characterized. The enzyme was a monomer with a molecular weight of 59,000. The optimum pH and the isoelectric point were 8.0 and 5.5, respectively. The enzyme catalyzed the hydrolysis of N-acyl derivatives of D glutamate. The Kms for N-acetyl, N-butyryl and N-propionyl derivatives of D glutamate were 0.129, 0.066 and 0.01 mM, respectively. PMID- 1894008 TI - Purification and partial characterization of ubiquitin-activating enzyme from Saccharomyces cerevisiae. AB - Ubiquitin-activating enzyme was purified from the yeast Saccharomyces cerevisiae by covalent affinity chromatography on ubiquitin-Sepharose followed by HPLC anion exchange chromatography. Enzyme activity was monitored by the ubiquitin-dependent ATP: 32PPi exchange assay. The purified enzyme has a specific activity of 1.5 mumol 32PPi incorporated into ATP.min-1.mg-1 at 37 degrees C and pH 7.0 under standard conditions for substrate concentrations as described by Ciechanover et al. (1982) J. Biol. Chem. 257, 2537-2542. The catalytic activity showed a maximum at pH 7.0. Its molecular weight both in non-denaturing and in SDS-gel electrophoresis was estimated to be 115 kDa, suggesting a monomeric form. The isoelectric point determined by gel electrofocusing was approximately 4.7. Two protein bands differing slightly in electrophoretic mobility could be distinguished when SDS gels were loaded with very small amounts of purified E1 and immunoblotted, the one with higher molecular weight being clearly predominant. The same two bands were also found in anti-E1 immunoblots of crude yeast lysates prepared under broad protease inhibition. PMID- 1894009 TI - Study of mammalian selenocysteyl-tRNA synthesis with [75Se]HSe. AB - The mechanisms of the synthesis of mammalian selenocysteyl-(Scy)-tRNA were studied using [75SE]H2Se. H2Se was prepared from [75Se]selenite, glutathione, NADPH and glutathione reductase, and was purified by chromatography. It was confirmed that this H2Se was a Se donor in the reaction of the synthesis of Scy tRNA. [75Se]Scy, liberated from aminoacyl-tRNA, was analyzed by TLC on silica gel an subsequent autoradiography. The activity of Scy-tRNA synthesis was found in the supernatant at 105,000 x g of the murine liver extract, but not in the precipitate. The supernatant was chromatographed on DEAE-cellulose, and the activity was eluted at a concentration of 0.17 M KCl. This position is at the front shoulder of the peak of seryl-tRNA synthetase which was eluted at 0.20 M KCl. Major serine tRNA(IGA) is not a substrate on which to synthesize Scy-tRNA, but natural opal suppressor serine tRNA is. On a chromatographic pattern of a Scy tRNA preparation on Sephacryl S-200, the radioactivity of 75Se was eluted at the tRNA peak. This showed that Scy bound to tRNA. The active protein fraction from DEAE-cellulose did not contain tRNA kinase, therefore Scy-tRNA must be directly synthesized from seryl-tRNA, not through phosphoseryl-tRNA. This mechanism is similar to that seen in Escherichia coli [1991, J. Biol. Chem. 266, 6324]. PMID- 1894011 TI - Molecular cloning of cDNA encoding the rat neural cell adhesion molecule L1. Two L1 isoforms in the cytoplasmic region are produced by differential splicing. AB - We have isolated and sequenced a full-length cDNA encoding the rat neural cell adhesion molecule L1. The deduced amino acid sequence as a whole shows high homology to mouse L1 sequence. In addition to this complete form of L1, we found an isoform, L1cs, which lacks four amino acid residues (RSLE) in the cytoplasmic domain and probably is derived from the same single L1 gene by tissue-specific alternative splicing. While L1 mRNA was predominantly expressed in the brain, L1cs mRNA was found exclusively in peripheral nervous tissue. Differential splicing in the highly conserved cytoplasmic domain may play an important role in modulating the function of L1 in different cells. PMID- 1894010 TI - Protein kinase C activity in rat skeletal muscle. Apparent relation to body weight and muscle growth. AB - Protein kinase C (PKC) may be involved in growth regulation. In the present study the relationship between body weight, and thereby age, and the activity of PKC in muscle as well as in rapidly growing overloaded muscle were investigated. PKC activity in music was linearly inversely correlated to rat weight in both soleus (r = -0.59, P less than 0.05) and in plantaris (r = -0.74, P less than 0.01) muscles. During compensatory hypertrophy. PKC activity per muscle was maximally increased compared with the contralateral control muscles after 4 days in both soleus (126%) and in plantaris (105%) but had returned to basal levels by the 9th day. The data are in agreement with a role for PKC in muscle growth. PMID- 1894012 TI - Laminin A-related domains in crb protein of Drosophila and their possible role in epithelial polarization. AB - It is shown that four domains of the integral membrane protein crb of Drosophila are homologous with five C-terminal domains of the laminin A chain and merosin. Since the latter domains of laminin A have been implicated in determining epithelial polarity, the homology may suggest a similar function for these domains of crb. Such a function would be consistent with the known importance of crb for organization of epithelia in Drosophila. PMID- 1894013 TI - Mifepristone (RU486) alone or in combination with a prostaglandin analogue for termination of early pregnancy: a review. AB - The availability of a medical mode of termination of early pregnancy by the administration of RU486, an antiprogesterone alone, or in combination with one of the PG analogues significantly reduces the maternal morbidity and mortality associated with the classical surgical abortion. RU486 given alone in early pregnancy induces complete abortion in 60% to 85% of cases, and when combined with prostaglandin analogues, gemeprost or sulprostone, reaches a success rate of 95% to 99%. RU486 may also be of potential value in the medical treatment of ectopic pregnancy. Its use as a postcoital contraception is suggested, but further research is required to determine whether RU486 can be used on a once-a month basis for contraception. PMID- 1894014 TI - Antiprogestins: the political chemistry of RU486. PMID- 1894015 TI - Revised guidelines for the use of semen donor insemination: 1991. The American Fertility Society. PMID- 1894016 TI - The appropriate upper age limit for semen donors: a review of the genetic effects of paternal age. AB - There is little evidence to support a correlation between increased paternal age and the incidence of chromosome anomalies. Though a few early studies demonstrated an increased risk of Down syndrome with advanced paternal age, especially after the age of 55, numerous later studies failed to confirm any paternal age effect. Among structural chromosome anomalies, only the inherited reciprocal translocations were found to be more common among children of older fathers. Chromosome analysis of semen donors would rule out this problem. There is evidence, however, that the incidence of serious nonchromosomal birth defects, especially those arising from new autosomal mutations, increases with paternal age. Risk estimates have been established for increased paternal age and contribution to new dominant mutations. The established association between increased paternal age and new autosomal mutations and the fact that most of the disorders associated with such mutations cannot be prenatally diagnosed may be important in establishing the upper age limit for semen donors. Recommendations from the literature are interpreted to advise men to have their children before age 40. This suggestion would obviously benefit immediate offspring and perhaps successive generations as well. The limit of 35 years set by AATB standards, therefore, is in harmony with such benefit, but may be too stringent in eliminating potential donors. Accordingly, the Reproductive Council of the AATB has initiated steps to modify its standards to the age limit of 40. PMID- 1894017 TI - The stimulus responsible for the peritoneal fluid inflammation observed in infertile women with endometriosis. AB - OBJECTIVE: We tested the hypothesis that menstrual debris from ectopic endometrium is the stimulus responsible for eliciting the peritoneal fluid (PF) inflammation observed in infertile women with endometriosis. DESIGN, SETTING, PATIENTS: The extent of endometriosis was correlated with the PF volume and total PF cell count retrospectively in 135 infertile women with endometriosis. RESULTS: The volume and total cell count were positively correlated, whereas the total cell count was negatively correlated with the extent of endometriosis. Despite a similar negative trend, no statistically significant correlation was noted between the volume and the extent of endometriosis. These relationships did not change when the data were reanalyzed deleting those pathological features contributing to the endometriosis score but not capable of producing intraperitoneal menstrual debris, i.e., adhesions and encapsulated ovarian endometriomas. CONCLUSIONS: These findings indicate that menstrual debris from ectopic endometrium is probably not a major factor in the elicitation of the observed PF inflammation in infertile women with endometriosis and suggest an inverse relationship may exist between PF inflammation and the extent of endometriosis. PMID- 1894018 TI - Retrograde seeding of endometrial epithelial cells by uterine-tubal flushing. AB - OBJECTIVE: To estimate the amount of endometrial epithelial cells in peritoneal fluid (PF) after uterine-tubal flushing (40 mL) throughout the menstrual cycle. DESIGN: We cultured the cell pellet of flush medium present in the peritoneal cavity. SETTING: University Hospital Nijmegen, The Netherlands. PATIENTS: Ninety two women with various infertility-related factors. INCLUSION CRITERIA: (1) ovulatory cycle, (2) patent tubes, and (3) no adhesions. INTERVENTIONS: None MAIN OUTCOME MEASURE(S): The number of developing epithelial cell colonies were counted after 7 days. We started to record the amount of flush medium recovered during the study. RESULTS: The amount of flush medium recovered was positively correlated with the presence of endometriosis (P = 0.017). Endometrial epithelial cells were identified in 85 flush media (92%). The number of epithelial cell colonies varied from 0 to 100 or more and was higher when flushing was performed during the early follicular phase (P less than 0.01). High estradiol-17 beta and progesterone levels in culture medium did not change the number of developing cell colonies. Methylene blue significantly reduced the number of cell colonies (P = 0.002). CONCLUSIONS: Uterine-tubal flushing results in varying numbers of endometrial epithelial cells in PF. Methylene blue adversely affects the growth potential of these cells. PMID- 1894019 TI - Late luteal estradiol patterns are a better prognosticator of pregnancy outcome than serial beta-human chorionic gonadotropin concentrations. AB - OBJECTIVE: Since the corpus luteum (CL) is known to play an important role in early pregnancy, its activity could possibly be a marker for pregnancy outcome. DESIGN: The late estradiol (E2) concentration in 48 viable pregnancies and 39 pregnancies which resulted in spontaneous abortions after in vitro fertilization and embryo transfer were used to evaluate such predictability. SETTING: All patients studied were of the Center for Reproductive Medicine at Cornell University Medical College. PATIENTS, PARTICIPANTS: Eighty-seven patients. INTERVENTIONS: None. MAIN OUTCOME MEASURE: Serum E2 and human chorionic gonadotropin (hCG) concentrations on day +11, +13, +15 (day +1 = day of ovum pick up) were measured and studied. RESULTS: The late luteal CL activity after rescue had a positive correlation with the number and quality of the implanted embryos. Reduced CL activity was indicative of abortion. The late luteal E2 pattern when compared with hCG doubling time had a better abortion predictability (37.8% versus 63.9%, respectively). CONCLUSION: Corpus luteum activity demonstrated to be a better prognosticator of abortion than serial beta-hCG titers. PMID- 1894020 TI - Effect of obesity on the response to acute adrenocorticotropin stimulation in eumenorrheic women. AB - OBJECTIVE: Alterations in adrenocortical biosynthesis, as measured by the steroid response to acute adrenocorticotropic hormone (ACTH) stimulation, have frequently been reported in female hyperandrogenism. These patients are also commonly obese, which may account for some of these abnormalities. The object of this study was to test the hypothesis that obesity alters the adrenal response to acute adrenal stimulation. DESIGN: A prospective study of healthy premenopausal women of varying weights. SETTING: University-based clinical research center. PATIENTS: Fifty-seven healthy, eumenorrheic, nonhirsute female volunteers were studied, 30 weighing between 90% and 110% (normal-weight) and 27 weighing greater than 120% (obese) their ideal body weight. INTERVENTIONS: All subjects underwent a 60 minute acute intravenous ACTH-(1-24) stimulation test in the follicular phase (days 3 to 8) of the menstrual cycle. MAIN OUTCOME MEASURES: The basal levels of dehydroepiandrosterone sulfate (DHEAS), total and free testosterone (T), sex hormone-binding globulin (SHBG), estrone, estradiol, prolactin, and the luteinizing and follicle-stimulating hormone ratio were measured. Basal and poststimulation levels of androstenedione (A), dehydroepiandrosterone (DHEA), 17 alpha-hydroxyprogesterone (17 alpha-OHP), 17-hydroxypregnenolone (17-PREG), 11 deoxycortisol (S), and cortisol (F) were also obtained, and the net increments after stimulation were calculated. RESULTS: Normal-weight and obese women did not differ in age, height, or waist-hip ratio. Obese volunteers demonstrated lower circulating SHBG, 17-PREG, and S levels, and S/F ratio, but a higher free T and DHEAS/DHEA levels. No other differences were observed in either basal or adrenal response measures, with the exception of the net increment in A, which was almost twofold higher in obese volunteers (P less than 0.001). CONCLUSIONS: Obesity in eumenorrheic nonhirsute women is associated with lower circulating SHBG activity and higher free T and DHEAS/DHEA levels. No significant difference in adrenocortical response to acute ACTH-(1-24) stimulation was observed between obese and normal-weight women, with the exception of a higher net adrenal output of A. It does not appear that the abnormal adrenal stimulation results frequently observed in hyperandrogenic women are a consequence of their obesity. PMID- 1894021 TI - Suppression of corpus luteum function by the gonadotropin-releasing hormone antagonist Nal-Glu: effect of the dose and timing of human chorionic gonadotropin administration. AB - OBJECTIVE: To assess the effect of gonadotropin-releasing hormone antagonist Nal Glu administration in the luteal phase and the potential rescue by exogenous human chorionic gonadotropin (hCG) of corpus luteum (CL) after antagonist treatment. DESIGN: We studied the dose of Nal-Glu required for luteolysis and subsequently we coadministered low doses of hCG for 3 consecutive days either simultaneously to Nal-Glu administration (n = 5), or 48 (n = 5), or 72 hours (n = 5) later. Six additional participants received pharmacological doses of hCG 48 hours after the luteolytic dose of Nal-Glu. SETTING: Participants were studied in Clinique Endocrinologique, Nantes, and in Service d'Endocrinologie, Hopital Bicetre, Le Kremlin Bicetre, France. PARTICIPANTS: Twenty-nine normal young women (ages 20 to 35) were studied. INTERVENTIONS: None. MAIN OUTCOME MEASURE: Measurements of follicle-stimulating hormone, luteinizing hormone (LH), estradiol, Progesterone (P) levels were performed by radioimmunoassay before, during, and after the various treatment regimens. RESULTS: Complete luteolysis occurred in women who received 10 mg of Nal-Glu daily on days 4 and 5 after the LH surge. The coadministration of Nal-Glu and hCG overrode the effect of the antagonist (P = 48.8 +/- 22.5 versus 60.8 +/- 3.1 nmol/L in controls treated with hCG alone [NS]). When hCG treatment was started 48 hours after Nal-Glu, a partial luteolysis occurred (P = 33.8 +/- 10.9 versus 117 +/- 12.9 nmol/L, P less than 0.01). When hCG was started 72 hours after Nal-Glu, a complete luteolysis occurred (P = 5.8 +/- 2.05 versus 36.2 +/- 0.6 nmol/L, P less than 0.01). Higher doses of hCG (1,500 or 5,000 IU) administered 72 hours after Nal-Glu resulted in a significant rescue of CL function (P = 37.7 +/- 4.8 and P = 43.8 +/- 22.2 versus 74.5 +/- 19.8 and 130.2 +/- 14.3 nmol/L, P less than 0.05), respectively. CONCLUSIONS: These results confirm the LH dependence of CL function. The suppression of CL LH support for 72 hours induced a compromise of the CL nonreversible by low doses of hCG mimicking early pregnancy but reversible with pharmacological doses. PMID- 1894022 TI - The relationship between female sexual practices and the development of antisperm antibodies. AB - OBJECTIVE: To determine if female sexual practices are associated with the development of antisperm antibodies. DESIGN: Anonymous questionnaire. SETTING: Tertiary care; private practice. PATIENTS: Thirty-nine consecutive patients undergoing antisperm antibody testing; 32 responded. INTERVENTIONS: Cervical mucus and serum obtained at midcycle. MAIN OUTCOME: Female sexual practices were found not to be related to the development of antisperm antibodies. RESULTS: The percent (44.4) of women with antisperm antibodies who practice anal intercourse was not different from the percent (35.7) without these antibodies who engage in the same practice, and the percent (94.4) of women with antisperm antibodies who practice oral intercourse was not different from the percent (92.8) without these antibodies who engage in this practice. CONCLUSION: Female sexual practices do not appear to be related to the development of antisperm antibodies. PMID- 1894023 TI - Cervical mucus score and in vitro sperm mucus interaction in spontaneous and clomiphene citrate cycles. AB - OBJECTIVE: Assessment of the effects of clomiphene citrate (CC) on cervical mucus score and in vitro sperm mucus interaction. DESIGN: Prospective study of cervical mucus score and in vitro sperm mucus interaction in a spontaneous cycle followed by a CC cycle to compare paired data. SETTING: Tertiary institutional infertility clinic. PATIENTS, PARTICIPANTS: Twenty-two couples with primary unexplained infertility were studied in both cycles. INTERVENTIONS: Clomiphene citrate (150 mg) on days 5 to 9 in CC cycles. MAIN OUTCOME MEASURES: Cervical mucus score and sperm-mucus penetration test score. RESULTS: Mean cervical mucus score in spontaneous cycles was 9.3 (95% confidence interval [CI] 8.4 to 10.2) and in CC cycles 5.6 (95% CI 4.6 to 6.6), P less than 0.0001. Sperm-mucus penetration test score in spontaneous cycles was 11.4 (95% CI 7.6 to 15.2) and in CC cycles 3.9 (95% CI 1.17 to 6.63), P less than 0.01. CONCLUSIONS: Clomiphene citrate has an adverse effect on both cervical mucus score and sperm-mucus penetration. PMID- 1894024 TI - Elevation of follicular phase inhibin and luteinizing hormone levels in mothers of dizygotic twins suggests nonovarian control of human multiple ovulation. AB - OBJECTIVE: To determine whether multiple ovulation in mothers of spontaneous dizygotic (DZ) twins is because of higher hypothalamic stimulation or is in response to lower serum levels of ovarian inhibin. DESIGN: Serum hormone levels were measured at five times throughout the cycle in a sample of eight mothers of DZ twins and paired controls. On day 12, ovarian ultrasonography was performed. SETTING: Blood samples were collected in participants' homes except on day 12 when they were collected at the ultrasonography clinic. PATIENTS, PARTICIPANTS: Human volunteers who had at least one set of spontaneous DZ twins were paired with controls matched for age and parity. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Serum inhibin, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) levels on approximate cycle days 1,2,8,12, and 21. RESULTS: Serum inhibin levels were elevated throughout the cycle (significantly on day 1) in mothers of DZ twins. Also elevated were early follicular FSH levels, LH levels throughout the follicular phase (significantly on days 1,2, and 8), and early to midfollicular E2 (significantly on day 8) in DZ mothers, indicative overall of greater follicular activity. CONCLUSION: It is concluded (1) that the primary cause of multiple ovulation in humans is not a decrease in inhibin secretion from the ovary; (2) the increased secretion of FSH and LH may be caused by elevated secretion of, or sensitivity to gonadotropin-releasing hormone; and (3) the elevated inhibin and E2 levels are a response to increased gonadotropin release. PMID- 1894025 TI - A human in vivo model for the luteoplacental shift. AB - OBJECTIVE: To study the onset of early placental steroidogenesis in humans. DESIGN: Ovarian failure patients who were administered a constant dosage of exogenous estradiol (E2) and progesterone (P) during the luteal phase and early gestation and who conceived after transfer of donated oocytes were used to assess serum hormonal changes throughout early pregnancy. SETTING: Hormonally replaced ovarian failure patients undergoing an egg donation program in an academic research environment. PATIENTS, PARTICIPANTS: Nine human volunteers desiring egg donation. INTERVENTIONS: Replacement of E2 and P. MAIN OUTCOME MEASURE: Serum E2 and P concentrations were measured weekly throughout the patients' gestations. RESULTS: Serum E2 and P levels of these patients remained low in early gestation but significantly increased 25 +/- 1.6 and 34 +/- 1.6 days post embryo transfer, respectively. Regression lines of E2 (r = 0.99; P less than 0.01) and P (r = 0.95; P less than 0.005), intersected basal hormonal levels approximately 3 weeks after transfer. CONCLUSION: This estimate of the onset of placental steroidogenesis is equal to the 5th gestational week as calculated by the patients' last menses, approximately 3 weeks earlier than previously reported. PMID- 1894026 TI - The prevalence, risks, and management of Chlamydia trachomatis infections in fertile and infertile patients from the high socioeconomic bracket of the South African population. AB - OBJECTIVE: The main objective of the study was to evaluate the prevalence of Chlamydia trachomatis endocervicitis in an infertile population. DESIGN: Forty consecutive patients were enrolled in the study group and 41 in the control group. SETTING: The study was undertaken in the Department of Obstetrics and Gynaecology of the University of the Orange Free State, Bloemfontein, Republic of South Africa. PATIENTS: Infertile white females, visiting an infertility clinic in an academic hospital and fertile white female patients visiting an antenatal clinic. INTERVENTIONS: Endocervical swabs were taken, and monoclonal direct immunofluorescence for C. Trachomatis were done on each. MAIN OUTCOME MEASURES: A difference was expected between the prevalence of C. trachomatis infection in the fertile and infertile population. RESULTS: In the study group, 14(35.9%) positive, 25(64.1%) negative, and 1 fallout were obtained. In the control group, 3 patients (7.32%) tested positive. CONCLUSION: Although no correlation was found between C. trachomatis infection of the female genital tract and the clinical history, it showed a significant correlation with infertility. This justifies routine screening tests and antibiotic treatment of positive infertile couples. Analysis of cost-effectiveness showed that empirical treatment of new infertile couples is justified in some populations. PMID- 1894027 TI - Psychological factors related to donor insemination. AB - OBJECTIVE: To survey a sample of couples who had completed therapeutic donor insemination (TDI) regarding several psychological variables. DESIGN: Couples who had conceived through TDI in the past 7 years completed a retrospective survey. PARTICIPANTS: Thirty-five of seventy couples returned completed questionnaires. MEASURES: Demographic questionnaire, TDI, and confidentiality questionnaire (created for this study), Dyadic Adjustment Scale. RESULTS: The majority of the subjects told at least one person about the TDI but 81% of subjects who told someone reported that, if they had to do it over again, they would tell no one. Eighty-six percent reported that they have not and will not tell the child. Time from diagnosis to beginning TDI was not correlated with marital adjustment after TDI. Overall, the couples reported average marital adjustment. For both men and women, the biggest concern was the genetic/medical history of the donor. Most couples did not have psychological counseling, but 39% thought it should be mandatory. CONCLUSIONS: Retrospectively, most couples regretted telling others about TDI. Most couples do not plan to tell the TDI child about its genetic origin. The major concern about TDI is the genetic and medical background of the donor. Psychological counseling should be available to couples undergoing TDI. PMID- 1894028 TI - Gamete intrafallopian transfer by hysteroscopy as an alternative treatment for infertility. AB - OBJECTIVE: To evaluate efficacy and safety of the hysteroscopic cannulation by flexible catheter of the fallopian tubes for gamete intrafallopian transfer (GIFT). DESIGN: We studied the pregnancy rate (PR) and the safety of this new technique. SETTING: All patients were enlisted for GIFT at our Reproductive Medicine Unit. PATIENTS: We treated 26 patients whose infertility causes were terminal tubal damage, male factors, unexplained factors, and endometriosis. Patients with uterine tubal ostia unsuitable for gamete transfer or cervical incontinence were not included in the group. INTERVENTIONS: The patients underwent ovulation induction and oocyte retrieval by transvaginal ultrasonically guided puncture. The gamete transfers were carried out by hysteroscopic procedure using a flexible catheter put through the operating channel. MAIN OUTCOME MEASURE: The efficacy was evaluated by the PR (25.9%). RESULTS: Seven clinical pregnancies were obtained, but two patients aborted during the first weeks of pregnancy. No ectopic pregnancies were observed. CONCLUSIONS: Our results indicate that hysteroscopic GIFT is an alternative, safe, effective, and not invasive technique for fertility problems. PMID- 1894029 TI - Predictive value of pregnancy during original in vitro fertilization cycle on implantation and pregnancy in subsequent cryothaw cycles. AB - OBJECTIVE: To understand the homogeneity of oocyte quality within a cohort. DESIGN: All women (n = 367) that had cryopreserved pre-embryos subsequently thawed were studied. Pregnancy and implantation rates in the in vitro fertilization (IVF) and cryothaw transfers were examined. SETTING: Tertiary care academic center. RESULTS: Pregnancy in original IVF cycle predicted higher implantation rates at subsequent cryothaw transfers. Similarly, pregnancy in cryothaw cycles was associated with higher implantation and ongoing pregnancy rates at the initial IVF cycle. CONCLUSIONS: Within a cohort of oocytes, pregnancy with some of the pre-embryos in a cohort predicts pregnancy with the remaining oocytes in the cohort. Thus, oocytes within a cohort have similar pregnancy potential. PMID- 1894030 TI - Elevated serum estradiol associated with increased androstenedione-testosterone ratio in adolescent males with varicocele and gynecomastia. AB - OBJECTIVE: To investigate the testicular function in adolescents with pubertal gynecomastia associated with varicocele before and after varicocelectomy. DESIGN AND PATIENTS: We have studied six male adolescents 15 to 19 years of age with bilateral gynecomastia. They were selected among other adolescents with gynecomastia because of the presence of visible varicoceles. All of them had normal physical examination and secondary sexual characteristics. This was prospective study of 3 months' duration. All the patients that were included finished the study. SETTING: All the patients were evaluated in the Endocrine Clinic of Winthrop-University Hospital, a tertiary care unit. INTERVENTION: Serum testosterone (T), androstenedione (A), and estradiol (E2) responses to the administration of human chorionic gonadotropin (hCG) 2,000 IU for 3 consecutive days before and 3 months after varicocelectomy were determined. RESULTS: Varicocelectomy did not cause any significant changes in the basal (pre-hCG) levels of the steroid. However, the increase in T levels achieved with hCG was significantly (P less than 0.005) higher after varicocelectomy (before T, 925 +/- 212 ng%; after T, 1,649 +/- 406 ng%). Simultaneously, the stimulated levels of E2 and A were significantly lower (P less than 0.005) after varicocelectomy (E2, 62 +/- 12 pg/mL; A, 326 ng% +/- 80 ng%) than before (E2, 106 +/- 13 pg/mL; A, 580 ng% +/- 95 ng%). CONCLUSION: The reciprocal effect on the levels of T and its immediate precursor, A, suggests an impairment of the 17-ketoreductase enzyme activity. The increased levels of E2 after hCG and its normalization after varicocelectomy suggests that varicoceles may play a pathogenetic role in the development of gynecomastia. PMID- 1894032 TI - The microsperm penetration assay: development of a sperm penetration assay suitable for oligospermic males. AB - OBJECTIVE: To develop a specialized sperm penetration assay (SPA) for the evaluation of sperm from oligospermic patients. DESIGN: The development of the assay is in four parts: determine optimal sperm number; demonstrate quality control; establish statistical limits for fertile population; compare results to in vitro fertilization (IVF) outcome. SETTING AND PATIENTS: A group of 63 patients with oligospermia and/or poor motility and a group of 17 fertile donors were compared using the optimized SPA and the micro-SPA. Sperm from a third group of 35 patients were simultaneously incubated with human ova (IVF) and hamster ova (micro-SPA). MAIN OUTCOME MEASURES: Both types of SPA scores are expressed as a sperm capacitation index (penetrations per ovum). Outcome of IVF is expressed as a percent of ova fertilized. RESULTS: Using 25,000 sperm was found to be optimal. The normal fertile range was statistically determined to have a lower limit (-2 SD) of 2.0 penetrations per ovum. When scores from 63 male factor patients were compared using the optimized SPA, only 43% had sufficient swim-up sperm. However, the micro-SPA could accurately test 100% of the samples because it requires only one tenth the number of sperm. CONCLUSION: The micro-SPA provides a valuable diagnostic test for the evaluation of the male factor patient. PMID- 1894031 TI - Occurrence of serum antisperm antibodies in patients with cystic fibrosis. AB - OBJECTIVE: To determine if acquired obstruction of the vas deferens in men with cystic fibrosis (CF) induced the development of antisperm antibodies with genital tract obstruction similar to other men. DESIGN: Serum antisperm antibodies were assayed by an indirect immunobead test and an indirect immunofluorescence assay. Both homologous (human sperm/human zona) and heterologous (human sperm/zona-free hamster ova) sperm/egg interactions were evaluated in the presence of serum antisperm antibodies from patients with CF. SETTING: Cystic Fibrosis Clinic at the University of Oklahoma Health Sciences Center, a tertiary care referral center. PATIENTS: Fifteen CF patients (10 male and 5 female), 3 non-CF antisperm antibody-positive infertile patients (2 male and 1 female), 20 fertile controls (7 males and 13 females), and 9 fertile sperm donors were used. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Serum antisperm antibody levels in patients with CF. In those patients with antisperm antibodies, determine effect of these sperm antibodies on sperm/egg interactions and complement-mediated events. RESULTS: Sera from 3 (30%) of 10 men with CF demonstrated immunoglobulin (Ig)G, IgA, and/or IgM antisperm antibodies, whereas sera from all 5 CF women and the 20 control sera were negative for antisperm antibodies. The maximal titers for IgG, IgA, and IgM antisperm antibody were 1:8, 192, 1:256, and 1:64, respectively. The immunobead binding, which was restricted to the sperm head and tail-tip or the midpiece and tail-tip, correlated with the indirect immunofluorescence pattern. Antisperm antibody-positive sera from men with CF impaired both the binding and penetration of human zonae and the penetration of hamster ova by human sperm. CONCLUSIONS: Similar to other men with congenital or acquired obstruction of their genital tract, antisperm antibodies may occur in some men with CF. Antisperm antibodies may contribute to immune sperm dysfunction in some men with CF by activated complement-mediated events and interfering with sperm/egg interactions. PMID- 1894033 TI - Vero cells stimulate human sperm motility in vitro. AB - OBJECTIVE: To study human sperm motility in a coculture system for in vitro fertilization (IVF). DESIGN: We studied the viability and motility (percentage and curvilinear velocity) of human spermatozoa after incubation in: (1) medium 199 supplemented with fetal calf serum (M199/FCS) together with Vero cells; (2) Vero cell conditioned M199/FCS; (3) M199/FCS supplemented with Vero cell extract; and (4) some control media. In a second experiment, FCS was substituted by sera from different IVF patients. SETTING: Semen samples were obtained from the fertility laboratory of the St. Radbound Hospital, Nijmegen, The Netherlands. PATIENTS: Twelve men of couples with fertility problems. INTERVENTIONS: None. MAIN OUTCOME MEASURE: The motility parameters were determined with a computerized motility-analyzing system, after 24 hours' incubation at 37 degrees C and 5% CO2. Viability was determined after eosin Y staining. RESULTS: Sperm viability was the same in all media. In the coincubation system, the Vero cell-conditioned medium, and the experiment with human sera, the sperm motility parameters were higher (P less than 0.005) than in the control media. Vero cell extract did not have this positive effect. CONCLUSIONS: Coincubation has a positive effect on sperm motility and may be beneficial to IVF, intrauterine insemination, and artificial insemination. PMID- 1894034 TI - Comparison of bicarbonate and HEPES-buffered media on pregnancy rates after intrauterine insemination with cryopreserved donor sperm. AB - OBJECTIVE: We compared the pregnancy rates (PRs) after intrauterine insemination (IUI) with frozen donor sperm prepared in Ham's F-10 medium (Irvine Scientific, Santa Ana, CA) with bicarbonate buffer and synthetic human tubal fluid with HEPES buffer (Irvine Scientific). DESIGN: Women (n = 101) were randomized upon entry into the program, receiving sperm prepared in either Ham's F-10 or human tubal fluid medium their first treatment cycle. If pregnancy did not occur, the alternate medium was used to prepared sperm for the following cycle. SETTING: All patients were treated in our private care center. PATIENTS: Patients entering this study were normally ovulating women undergoing IUI with frozen donor sperm. MAIN OUTCOME MEASURE: Pregnancy was used as our main outcome measure of success. RESULTS: After 324 cycles of treatment, the PR per cycle of IUI was 17.5% with sperm prepared in human tubal fluid which was significantly different (P = 0.05) from the PR (9.8%) after insemination with sperm prepared in Ham's F-10. There was no statistical difference in the number of motile cells inseminated in each of these groups. CONCLUSIONS: Transitory exposure of the sperm in Ham's F-10 medium to the environment during preparation for insemination may result in an alkalinization of the medium that has a lasting influence on sperm fertility. PMID- 1894035 TI - Depletion of luteal phase serum progesterone during constant infusion of cortisol phosphate in the cynomolgus monkey. AB - OBJECTIVE: To study the impact of chronic infusions of cortisol phosphate on ovarian function in the cynomolgus monkey. DESIGN: Cortisol phosphate at doses of 5 or 15 mg/d or saline were infused for periods of up to 8 weeks using subcutaneously implanted osmotic pumps. SETTING: Animals were maintained in the Center for Experimental Animal Resources, Northwestern University. MAIN OUTCOME MEASURES: Serum total and unbound cortisol concentrations, serum total and unbound progesterone (P) concentrations, urinary P metabolites. RESULTS: Mean increases in serum cortisol of 56% and 77% above control levels were achieved. Mean serum P concentrations were not decreased with low-dose cortisol phosphate infusion during the 12 days preceding menses, but mean serum P levels were decreased by 69% to 2.3 ng/mL during high-dose cortisol phosphate infusion. No corresponding decrease in excretion of conjugated immunoreactive P metabolites was found in daily urine samples during cortisol phosphate infusion, suggesting that production rates of P were unaltered by the cortisol phosphate treatment. Unbound serum cortisol increased by a mean of 162% above control levels during high-dose cortisol phosphate infusion, but no increase occurred in the percentage of unbound serum P. CONCLUSIONS: We conclude that elevation of serum cortisol in the range observed in chronically stressed individuals may severely decrease the available P to target organs by displacement of P from plasma proteins but does not inhibit ovarian steroidogenesis or ovulation. PMID- 1894037 TI - Effect of hyaluronic acid on postoperative intraperitoneal adhesion formation in the rat model. AB - OBJECTIVE: The aim of this study was to determine the effectiveness of hyaluronic acid solution in preventing intraperitoneal (IP) adhesions. DESIGN AND SETTING: The study design was prospective, randomized and blinded and involved 83 rats. INTERVENTIONS: Measured serosal injury was inflicted using a CO2 laser on the right uterine horn of the rat. Animals randomized to groups 1 and 2 received either 0.4% hyaluronic acid or its diluent phosphate-buffered saline (PBS) intraperitoneally before and after the injury. In groups 3 and 4, the same solutions were used only after the injury. Postoperative adhesions were assessed at second-look laparotomy. Histologic assessment of the fresh laser injury was carried out on uteri pretreated with hyaluronic acid, PBS, or nothing. MAIN OUTCOME: Pretreatment with hyaluronic acid was associated with a significant reduction in postoperative adhesions and a significantly decreased crater depth. CONCLUSIONS: Hyaluronic acid appears to reduce postoperative IP adhesion formation by coating the serosal surfaces and decreasing the extent of initial tissue injury. PMID- 1894036 TI - Factors that influence fertility after vasovasostomy in rats. AB - OBJECTIVE: To determine if fertility after vasovasostomy of immunologically responsive Lewis rats differs from that of the less responsive Sprague-Dawley strain and to relate fertility to antisperm antibodies, fluid flow in the vas deferens, and testicular structure. DESIGN: Male rats received: (1) bilateral vasectomies; (2) vasectomies followed 3 months later by vasovasostomy; or (3) sham operations. SETTING: Research laboratory. MAIN OUTCOME MEASURES: Fertility was assessed by caging males with three females for 2 weeks and subsequently counting implantation sites. Antisperm antibodies were measured with an enzyme linked immunosorbent assay, fluid flow through vas deferens segments was tested in vitro, and testicular structure was studied microscopically. RESULTS: Nearly all vasovasostomized Lewis rats were infertile (33 of 34), whereas 62% (18 of 29) Sprague-Dawley rats were fertile after vasovasostomy (P less than 0.001). In fertile Sprague-Dawley males, significant correlations existed between: (1) implantation sites or females impregnated; and (2) antisperm antibodies early after vasectomy, vas flow, and testicular morphology. CONCLUSIONS: Genetic differences affect fertility after vasovasostomy. Fertility after vasovasostomy is also influenced in a multifactorial manner by the immune response, mechanical elements, and structural changes in the reproductive tract. PMID- 1894038 TI - Effect of hyaluronic acid on postoperative intraperitoneal adhesion formation and reformation in the rat model. AB - The local application of 0.25% or 0.4% HA before the induction of a measured laser injury on the rat uterine horn was associated with a significant reduction (P less than 0.05) in postoperative IP adhesions when compared with the group of animals pretreated with the diluent vehicle PBS or received no pretreatment. However, 0.4% HA, when applied in a similar manner, was ineffective in reducing reformation of adhesions after microsurgical adhesiolysis. PMID- 1894039 TI - Changes in body composition with danazol therapy. AB - Whole body lean and fat mass measurements by dual energy x-ray absorptiometry were performed in 14 premenopausal women undergoing danazol treatment for endometriosis. After 6 months, there was a significant increase in lean tissue mass. Body fat decreased but this was significantly less in the android (upper body segment) region than in the gynoid (lower body segment) region. Danazol thus has both anabolic and androgenic effects on body composition. Dual energy x-ray absorptiometry provides a new, noninvasive, and rapid means of studying body composition. PMID- 1894040 TI - Mayer-Rokitansky-Kuster-Hauser syndrome associated with endodermal sinus tumor of the ovary. AB - Both EST and Mayer-Rokitansky-Kuster-Hauser syndrome are uncommon disorders. This report illustrates a case of these two rare conditions occurring in the same patient. Patients with Mayer-Rokitansky-Kuster-Hauser syndrome, although not appearing to be at increased risk for germ cell tumors, unlike testicular feminization patients, are not immune to ovarian cancer. Therefore, individuals with Mayer-Rokitansky-Kuster-Hauser syndrome should still be followed gynecologically because they are at least at the normal risk of developing ovarian as well as other gynecological neoplasms. PMID- 1894041 TI - The place of in vitro fertilization in the treatment of tubal disease. PMID- 1894042 TI - Bulimia and polycystic ovarian syndrome? PMID- 1894043 TI - Immediate transfer of gametes to uterus. PMID- 1894044 TI - Scientific distillates versus full papers. PMID- 1894046 TI - [The nature of and the interrelations between the concepts of "life","disease" and "aging"]. AB - An attempt is made to consider disease and aging following from the concepts of the essence of life. The proposed definition of life represents a modified Engels' (1878) definition. Proceeding from the analysis of possible mechanisms of different disturbances in the life process leading to a decreased probability of the organism existence it is concluded that disease develops either as a result of hereditary changes in the genome or due-to disorders in its realization under certain unfavorable conditions. Aging is determined by the properties of the genome itself and develops in connection with age increase. PMID- 1894045 TI - [Serum acid phosphatase activity in rats with hypoxia of different etiologies]. AB - Experiments on male rats have shown that the acid phosphatase activity increases in all the types of hypoxia (circulatory-hemic, hemic and hypoxic), in blood serum. An increase in the activity of this enzyme distinctly correlates with hypoxia gravity. A supposition is advanced that the blood enzyme level of lysosomal hydrolases can reflect the functional state of the lysosomal apparatus in cells of the organism. PMID- 1894047 TI - [Prevention of myocardial reperfusion injury by increasing artificial trans membrane sodium gradient in "calcium paradox" and post-ischemic reperfusion]. AB - An effect of the high sodium gradient during "calcium paradox" and postischemic reperfusion has been studied. A decrease of Na/Ca exchange by high sodium gradient (200 mM NaCl in the perfusion solution) resulted in the reduction of myoglobin release from the heart during "calcium paradox". High sodium concentration solution (200 mM) increased protective effect of ATP during "calcium paradox". Exogenous phosphocreatine (100 mumol/mol) increased myoglobin release from the heart. During perfusion of the heart by high sodium concentration, phosphocreatine efficiently decreased myoglobin release from the heart during "calcium paradox". Exogenous ATP (as Na-pump activator) and high Na+ concentration solution (180 mM) prevented the LDH release from the myocardium, decreased ATP hydrolysis, inhibited Ca influx, maintained total adenine nucleotides, phosphate potential, energy charge of the cardiomyocytes. PMID- 1894048 TI - [Non-invasive evaluation of systolic and diastolic functions of the left ventricle in newborn infants]. AB - To assess possible changes in myocardial contractile function and relaxation occurring after mild perinatal asphyxia, maximal blood pressure and M-mode echocardiograms should be registered simultaneously in 32 normal term newborns (group 1) and in 22 term asphyxiated newborns (group II). The slope of end systolic pressure-dimension relation (ESPDR) was used as a reliable index for evaluation of the myocardial contractility. The slope of ESPDR and some indices of ventricular relaxation decreased in newborns from group II. It is suggested that ESPDR and parameters of left ventricular relaxation and filling can serve as early and sensitive indices of hypoxic myocardial damage. PMID- 1894049 TI - [Age-related characteristics of the role of the endothelium in the response of vascular smooth muscles to hormones. The role of ultrastructural changes]. AB - The experiments performed on isolated preparations of femoral artery and aorta of the mature and old rats as well as on those of coronary arteries of adult and old subjects failed to reveal direct participation of endothelium in the realization of insulin and vasopressin effects on the smooth muscles of the vessels studied. However, the endothelium modulated their influence on the vessels in the mature age. The lack of modulating effect of the endothelium in old age may be a result of its structural changes and thickening of a hemato-cellular barrier of the vessel wall observed by electron microscopy. PMID- 1894050 TI - [Structural characteristics of dry blood serum of patients with arteriosclerosis after plasmapheresis]. AB - The surface of dried drops of blood serum (BS) from 86 plasmapheresis patients with atherosclerosis has been studied for its structural peculiarities. The content of lipids (total cholesterol, cholesterol of lipoproteins of high density, triglycerides), sialic acids and immunoglobulins was determined in all the examinees. BS from 20 practically healthy people was taken as a control. Optically inactive filamentous dichotomically branching crystals were typical of its microstructure. Optically active spherolites were found in patients with high content of cholesterol, optically active dendrite aggregation--in patients with high content of triglycerides, optically active fibrils appeared in case of hypersialemia, optically inactive aggregates--in case of hyperimmunoglobulemia. The plasmapheresis course carried out in patients was followed by appearance of filamentous dichotomically branching crystals, and disappearance of optically active inclusions, that testified to ordering of the BS structure. The results obtained were confirmed by normalization of the content of lipids, sialic acids, immunoglobulins. PMID- 1894051 TI - [Temperature sensitivity and the indicators of respiration in humans in the normal state and during local cooling]. AB - The examination has shown that people who have many cold spots on the forearm possess high ventilation volume and breathing frequency and low value of oxygen utilization. These facts can evidence for the effect of cold skin receptors on the respiratory patterns. The skin temperature, at which the maximal cooling induced changes of respiratory parameters are observed depends on the dynamic activity of cold skin thermoreceptors: the greater number of cold spots in the hand and forearm, the lesser cooling is necessary to cause the maximal increase of oxygen consumption and change of respiratory volume. The latter increased in the case of hand cooling and decreased in the case of the forearm cooling. PMID- 1894052 TI - [Physical exercise and the quantitative characteristics of moisture- excreting function of the lungs]. AB - Physical loading has been used as a test to study the regulation of moisture excretion in the act of breathing in 101 healthy students, 62 men with external risk factors, and in 73 patients with respiratory diseases (chronic bronchitis, acute pneumonia, bronchial asthma). The correlation of moisture excretion with the parameters of ventilation, age, sex, body weight of examinees proved that physical loading in the age-groups above 50 with excess body weight and with hyperventilation resulted in blocking effect on the volume of moisture loss during breathing. Thus, these endogenic factors determine the individual reaction in dynamics of moisture loss during physical loading and could be considered as risk factors in deteriorations of moisture excreting function of lungs. PMID- 1894053 TI - [Electric and mechanical activities of the upper esophageal sphincter in rabbits]. AB - Electrical and mechanical activities of the rabbit muscles in different zones of the esophageal cervical part were examined on free-moving rabbits with chronically implanted electrodes and force transducers under conditions of hunger and food intake. It is shown that the functional role of the circular muscles of the cranial end of the esophagus is determined by their participation in activity of the superior esophageal sphincter. PMID- 1894055 TI - [Effect of chorionic gonadotropin on the structure and endocrine function of the thymus gland in mice]. AB - The thymic secretory function changes in the pubertal female mice under the influence of chorionic gonadotrophin (CG). The latter is activated after administration of hormone in doses, corresponding to its levels in animals in different terms of pregnancy and is depressed with doses, greatly exceeding those levels. The lack of the effect in thymectomized mice testifies to the realization of the modulating CG action at the thymus level. Changes of mass and cellularity of the thymus and spleen reflect dose-dependent alteration of the thymocyte migration rate. PMID- 1894054 TI - [Comparative evaluation of the protective effect of sodium valproate, phenazepam and ionol in stress-induced liver damage in rats]. AB - Ionol, a synthetic antioxidant, limits the stressor liver injury to a greater extent than sodium, valproate and phenazepam, activators of a GABA-ergic link of the stress-limiting organism systems. This injury is exhibited in the organospecific elevated levels of blood enzymes fructosediphosphate aldolase depression of N-demethylase activity of microsomal monooxygenases and a decrease in the amount of cytochromes P-450 and B5. PMID- 1894057 TI - [The role of oxygen-binding properties of hemoglobin in the development of oxygen deficiency in acute exogenous hyperthermia]. AB - Acid-base balance and oxygen-binding hemoglobin properties in mixed venous blood have been studied in 25 mongrel rabbits with acute environmental hyperthermia. As oxygen-hemoglobin affinity at standard pH, pCO2 and temperature increases, the effect of heat on oxygen-hemoglobin interaction is considerably attenuated. The Bohr effect increases. The mechanisms of changes in oxygen-binding properties of hemoglobin and their role in development of oxygen deficiency are discussed. PMID- 1894056 TI - [Differences in the mechanisms of thermoregulation in rats in separate and combined adaptation to cold and heat]. AB - Combined adaptation of rats to heat and cold increasing mechanisms of thermogenesis enhances resistance to both factors and heat dissipation. Adaptive changes in thermogenesis are mainly a result of activation of adrenergic mechanisms, while the separate cold adaptation is accompanied by hyperfunction of thyroid glands. Mechanisms of heat dissipation in rats of the "combined" group increase even more than those of "heat" group. PMID- 1894058 TI - [Effect of adaptation to periodic hypoxia on post-infarction fall of blood pressure and hyperactivation of the endothelium]. AB - Acute stress concomitant to the experimental myocardial infarction has induced endothelial hyperactivation of the rat aorta exhibited in an increase of inhibition of norepinephrine-induced contractions of vascular smooth muscle, enhanced endothelium-dependent relaxation correlating with a fall of systemic blood pressure. Preliminary adaptation of rats to intermittent hypobaric hypoxia greatly prevented the stress-induced endothelial hyperactivation and beneficially affected the postinfarction time course of blood pressure. PMID- 1894059 TI - What are nurses' attitudes, knowledge and practice of the universal precautions policy? PMID- 1894060 TI - AIDS Task Force update: nurses caring for nurses. PMID- 1894062 TI - Psychology of mind and nursing: a journey within. PMID- 1894061 TI - First experiences shape nursing practice. PMID- 1894063 TI - Nursing's agenda for health care reform. PMID- 1894064 TI - Registered nurses: an attractive market for power and revenue. PMID- 1894065 TI - On the nursing shortage: supply of registered nurses in Florida. PMID- 1894066 TI - The nursing shortage: crisis as opportunity. PMID- 1894068 TI - The mark of a good preceptor. PMID- 1894069 TI - Army field nurses: caring for American forces. PMID- 1894067 TI - Teachers reach out to new families. PMID- 1894070 TI - Navy Lt. Thornton deployed for Desert Shield/Storm. PMID- 1894071 TI - Why should I become a navy nurse? PMID- 1894072 TI - Desert Storm--stateside: reflections of an army nurse. PMID- 1894073 TI - The dual mission of the National Guard in "Caring for America". PMID- 1894074 TI - New diagnostic modalities for the evaluation of the patient with syncope. AB - Syncope is a common clinical problem. Patients with cardiac syncope have a poor prognosis and a high incidence of sudden death during follow-up. The most common diagnosis in these patients is ventricular tachycardia in the setting of coronary artery disease. Patients with syncope and structural heart disease should undergo EP testing to exclude ventricular tachycardia. The use of SAE may be helpful in selecting patients who are likely to have ventricular tachycardia at EP testing. Patients with syncope and a normal heart have an excellent survival, but about 30 percent have recurrent spells. Those patients with a normal heart and syncope in the upright position often have neurally mediated syncope, and the diagnosis can be confirmed by tilt testing. Patients defying diagnosis should undergo loop monitoring to document the cardiac rhythm during syncope. PMID- 1894075 TI - Bolus administration of 5 mg epinephrine as a treatment of last resort for cardiac arrest. AB - There is some evidence that the dose of epinephrine currently recommended for resuscitation is low. This study examines the effect of bolus administration of 5 mg of epinephrine when given as an agent of last resort for cardiac arrest. The experimental design called for the administration of high-dose epinephrine at the point where resuscitative efforts would have ordinarily been stopped. Resuscitation was then continued for a minimum of five minutes so that any changes in rhythm or return of spontaneous circulation could be noted. Eighty five consecutive patients undergoing resuscitation in our Emergency Department were enrolled in this study. Twenty-eight (33 percent) exhibited a change in cardiac rhythm. Of these 28 patients, seven (8 percent) developed pulses. Of these seven patients, four expired in the Emergency Department, one survived to admission but expired two days later, and two patients survived to discharge. We conclude that bolus administration of 5 mg of epinephrine may be useful in treating cardiac arrest refractory to conventional therapy. PMID- 1894076 TI - New legal trap for the incorporated physician. PMID- 1894077 TI - Access to care. PMID- 1894078 TI - [The trigeminal and pain. Anatomy, physiology and clinical picture. 1]. PMID- 1894079 TI - [Dry compressors. Characteristics and utilization]. PMID- 1894080 TI - [Apical resorption in pre-surgical orthodontics]. AB - Apical root resorption is a frequent phenomenon observed in pre-surgical orthodontic; the reason is double: we deal with adult patients and we often move the teeth in the opposite direction compared to the position obtained in previous inefficacious orthodontic treatments. Notwithstanding the amount of apical root resorption we couldn't record an hyper-mobility of the teeth and a long term evaluation of occlusal stability didn't show any significant change. PMID- 1894081 TI - [The external pterygoid muscle. Functional aspects]. AB - This study, starting from the revision of traditional anatomy proposed to value TMJ and its components through dissection of human TMJ, and especially to examine the anatomic function of the lateral pterygoid muscle. Twenty dissections of left human TMJ were made. Every block was fixed in solution of 10% of formalin and dissections were made to show every components of articulation. Further thin sections were made for histological examination. The purpose of the study was to evaluate the lateral pterygoid muscle as a single unit compared to the function. PMID- 1894082 TI - [Cyanoacrylates as a cementation material in fixed prosthodontics]. AB - The purpose of this study was to examine and compare, in the same experimental conditions, the effects and the behaviour of two different materials, using them for cementation of a prosthetic reconstruction: a cianoacrilic compound (B20 cianoacrilate 3M); a traditional cement of zinc phosphate (Harvard Cement). The comparative study with the optical microscope between butilcianoacrilate and traditional cement has shown minimum levels of marginal discrepancy for both materials examinated (about 13 microns). The high resistance of cianoacrilate to traction, compared with the other fixing cement, makes us conclude this study in the hope that further research could confirm and introduce this materials in the practice of prosthetic dentistry. PMID- 1894083 TI - Giving computerization a human face. PMID- 1894084 TI - In-house servicing of microcomputers. PMID- 1894085 TI - The smart card: a tool for smart hospitals. PMID- 1894086 TI - New bar coding tools for clinical managers. PMID- 1894087 TI - Security precautions for networked computers. PMID- 1894088 TI - [Computerization of a small hospital]. PMID- 1894089 TI - Networked computerization in a community hospital. PMID- 1894090 TI - AZT patent challenge. PMID- 1894091 TI - Health technology news. Assessing effectiveness: databases can help. PMID- 1894092 TI - [The characteristics of water-salt metabolism, kidney functions and the mechanisms of their regulation in youth]. PMID- 1894093 TI - [A taxonomic analysis of individual body reactions to a test hypoxic exposure]. PMID- 1894094 TI - [The dynamic characteristics of the human motivational sphere during food deprivation]. PMID- 1894095 TI - [The typological patterns of the protective reactions under chronic physiological tension]. PMID- 1894096 TI - [The characteristics of the adaptive adjustments in the participants in the Soviet-American Bering Bridge expedition. I. The energy aspects of adaptation]. PMID- 1894097 TI - [The mechanisms of the efficiency of intellectual activity]. PMID- 1894098 TI - [Experience in using automated systems for assessing body functional characteristics. III. The functional indices of subjects engaged in intellectual work]. PMID- 1894099 TI - [Biological age and physical work capacity in the prenosological diagnosis of the workers and employees in a ship-building enterprise]. PMID- 1894100 TI - [Changes in the nature of autonomic functional regulation in female microcircuit assemblers during training and work]. PMID- 1894102 TI - [The level of physical work capacity of drivers as an index of their reliability]. PMID- 1894101 TI - [The laterality characteristics in human perception of emotional information]. PMID- 1894103 TI - [The significance of the interaction of the temporal and parietal cortices during visual perception]. PMID- 1894104 TI - [The effect of functional and organic disorders in the visual system on the amplitude-temporal characteristics of evoked potentials]. PMID- 1894105 TI - [The repeated dichotic testing of subjects with a favored left ear]. PMID- 1894106 TI - [A method for the rapid diagnosis of human psychoemotional stability]. PMID- 1894107 TI - [A polyelectroneurographic study of the spatial coherence of gradual processes in the human brain. II. The evaluation of the dynamic elements of the communications structure]. PMID- 1894108 TI - [The reactive characteristics of the cardiovascular system to mental and physical loads in healthy subjects and in persons with borderline arterial hypertension]. PMID- 1894109 TI - [The dynamics of the pumping and contractile functions of the heart under a graded isometric pedal load]. PMID- 1894110 TI - [The "double product" in the diagnosis of cardiovascular system function]. PMID- 1894111 TI - [The significance of the level of physical and sexual development of prepubescent girls for sports selection]. PMID- 1894112 TI - [The expenditure of muscle glycogen during high-intensity short-term work in relation to its initial content]. PMID- 1894113 TI - [The assessment of physical work capacity in excessive body weight]. PMID- 1894114 TI - [The variability of the normal values of the biochemical indices of human blood]. PMID- 1894115 TI - [The characteristics of the leukogram of healthy subjects in an industrial region of the steppe zone of the Ukraine]. PMID- 1894116 TI - [The effect of hyperthermia on human hormonal and immune indices]. PMID- 1894117 TI - [The concentration of copper in the blood of healthy subjects under muscle loads and its seasonal dynamics]. PMID- 1894118 TI - [The echo-dipyridamole test early after acute myocardial infarct: echocardiographic aspects and angiographic correlations]. AB - To assess whether the different mechanical effects of intravenous dipyridamole were correlated with the location and distribution of the coronary arteries stenosis, 98 patients underwent high dose DET 8-10 days after an acute myocardial infarction. Left ventricular regional wall segments were identified in multiple views; a vascular territory was assigned to each coronary vessel. DET was positive in 68.4% of the patients (67/93), 59% (23/39) of those with single vessel disease, and 81% (44/54) of those with multivessel disease. Four different mechanical patterns of positivity of DET were observed: 1) marked worsening of wall motion in the same region showing asynergy (type I); 2) development of new wall motion abnormality adjacent to the infarct zone and located in the same vascular region (type II); 3) development of new wall motion abnormality adjacent to the infarct zone, but located in a different vascular region (type III); 4) development of transient remote asynergy (that is, a new wall motion abnormality in a region normal at rest and not directly adjacent to the infarct zone, type IV). Types I and II (asynergies in the infarct zone coronary bed) were found in patients both with single vessel disease or multivessel disease; by contrast, type III and IV were almost exclusively found in patients with multivessel disease (24/54 and 14/54 respectively) and occasionally in patients with single vessel disease (2/39 and 1/39 respectively). Thus, these two mechanical behaviours during dipyridamole infusion showed to be highly specific for predicting multivessel disease (95% and 97% respectively, sensitivity 44% and 26% respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1894119 TI - [Doppler ultrasound in the diagnosis of renal artery stenosis in hypertensive patients: a prospective study]. AB - Renal artery stenosis is the most common surgically or interventionally curable cause of hypertension. Screening and diagnostic tests are still needed to establish the presence of renal artery stenosis. The aim of our study was to evaluate sensitivity, specificity and diagnostical accuracy of renal artery duplex scanning for diagnosis of renal artery stenosis in hypertensive patients. Between January 2, 1988 and December 31, 1989 we performed renal artery duplex scanning in 128 hypertensive patients in whom were present clinical data suggestive of renal artery stenosis. Angiographic evaluation was performed within 3 months in 23 patients with a positive duplex, and in 15 patients with a negative duplex but highly suggestive for renal artery stenosis clinical data. Studies were performed with an Ultramark 8 duplex scanner (ATL). Data of this report are relative to the analyses performed of 76 renal arteries. Duplex scanning had a sensitivity of 90% and specificity of 96% to detect renal artery stenosis. Diagnostic accuracy was 93% for 50% to 60% stenosis and 100% for occlusion or 60% to 99% renal artery stenosis. Duplex scanning for diagnosis of renal artery stenosis shows agreement with angiography. Duplex scanning, which can distinguish high grade stenosis from occlusion, is able to select patients for possible percutaneous transluminal angioplasty before angiography, and we consider duplex scanning a valid, noninvasive screening or diagnostic test for renovascular hypertension. PMID- 1894120 TI - [Treatment of malignant ventricular tachyarrhythmia with amiodarone: comparison of empirical administration and administration guided by Holter or ventricular stimulation. Results of the parallel test]. AB - To assess the most appropriate method of administering amiodarone and predicting its efficacy (empiric vs guided by Holter or by ventricular stimulation), 19 patients with sustained ventricular tachycardia or ventricular fibrillation underwent a "parallel study". Fifteen patients were men and 4 women, with a mean age of 65 years. A coronary artery disease with previous myocardial infarction was present in 15 patients, dilated cardiomyopathy in 3 and arrhythmogenic right ventricular dysplasia in 1 (mean left ventricular ejection fraction = 35%). All 19 patients had, as inclusion criteria, 1) frequent (greater than or equal to 30/hour) and/or repetitive (greater than or equal to 10/24 hours) ventricular premature beats during 24-hour Holter monitoring and 2) inducible sustained (greater than 30/sec) ventricular arrhythmias during programmed ventricular stimulation (1-3 extrastimuli from 2 right ventricular sites). Amiodarone was given at an initial dosage of 15 mg/kg/day for 2 weeks and then at a dosage of 5 mg/kg/day. After 15 days 24-hour Holter monitoring and programmed ventricular stimulation were repeated. The data of these tests, however, were not used to guide the therapy that remained empiric, but served only to assess retrospectively the predictive value of Holter monitoring and ventricular stimulation. The following main results were obtained: The mean duration of follow-up was 25 +/- 13 months. During this period 6 patients (32%) died, 3 from sudden and 3 from non-sudden cardiac death. Two other patients had recurrence of sustained ventricular arrhythmias. After 15 days of therapy amiodarone was effective at Holter monitoring in 15 patients (79%) and not effective in 4 (21%). Two of the 15 patients considered responders died suddenly during the follow-up and 2 had arrhythmic recurrence, vs 1 of the 4 non-responder patients who died suddenly (negative predictive value of Holter monitoring: 73%; positive predictive value: 25%; predictive accuracy: 63%). After 15 days of therapy amiodarone was effective at ventricular stimulation in 10 patients (53%) and not effective in 9 (47%). None of the 10 patients considered responders had arrhythmic events during the follow-up, vs 5 of the 9 non-responders, 3 of whom died suddenly and 2 of whom had arrhythmic recurrences (negative predictive value of ventricular stimulation: 100%; positive predictive value: 56%; predictive accuracy: 79%). Only 1 patient discontinued amiodarone after 25 months of follow up because of development of an important blue-grey skin discoloration.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1894121 TI - [Echocardiographic evaluation of HIV-positive subjects]. AB - The purpose of the study was to assess the prevalence and the type of cardiac abnormalities in patients with HIV infection. Echocardiographic examination (M mode, two-dimensional and Doppler) was performed in 51 patients (40 male, 11 female), whose mean age was 29 +/- 10 years; 48 of them (94%) were intravenous drug addicts, 3 (6%) homosexuals. Diagnosis was AIDS in 19 (37%) patients, AIDS related complex in 19 (37%) and asymptomatic infection in 13 (26%). Echocardiography was normal in 13 subjects. Pericardial effusion was found in 19 patients (in 8 of them, this was the only cardiac abnormality). Valve vegetations were found in 16 patients (3 of them had pericardial effusion, 5 had ventricular dilatation or wall motion abnormalities, 1 had both pericardial and myocardial impairment). Myocardial dysfunction was found in 18 patients: 11 had left ventricular dilatation (5 with wall hypokinesia), 1 had right ventricular enlargement, 1 had biventricular dilatation and 5 had only wall motion abnormalities (diffuse or localized). During the follow-up 9 patients died: 8 had AIDS, 1 was asymptomatic. Eight subjects died during hospitalization (none because of cardiac causes) and one at home for sudden unexplained death. Echocardiography had displayed myocardial dysfunction in 6 of them, thickened pericardium in 1 and was normal in 2. Pathologic examination (performed in 8 subjects) showed cardiac enlargement in 3 subjects, thickened pericardium in 2 and valve vegetation in 1. One subject had histopathologic diagnosis of myocarditis and 7 had non specific histologic abnormalities. The study shows a cardiac involvement in 75% of HIV infected patients: 35% had myocardial dysfunction, 37% pericardial disease, 31% infective endocarditis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1894122 TI - [Comprehensive computer-assisted management of a cardiology department]. AB - We are proposing a personal computer local network system for collecting data and managing of both cardiovascular in- and outpatients. The six PCs used as work stations are located in the following areas: reception desk, ergometry, holter, echocardiography, secretarial and coronary care unit and cardiology department. Starting from a commercially available DBMS program, an "Iceberg" applied program was first made in a single personal computer and then transferred to a local network. The tree-structured data base includes the cardiopathies list, the vasculopathies list, some cardiovascular clinical data and all information regarding cardiological instrumental tests. The data are descriptive, numeric, date, text and comment. The operative program allows us to change the data base without the help of the software house staff, so the system is adaptable to cardiological departments with different instrumental equipment and sections. The report of instrumental tests and the issuing of the discharge letter are made with the local work station, with simultaneous compiling, storing and printing. It is then possible, using any work station, to restore and print quickly a summary of all data concerning each patient. This summary permits us, in nearly all cases, to identify the patient's history and present condition, as well as the diagnostical steps taken. PMID- 1894123 TI - [Interventional and induction cardioarrhythmology. Electropharmacological intervention]. PMID- 1894124 TI - [Interventional and induction cardioarrhythmology. Electric intervention]. PMID- 1894125 TI - [Interventional and induction cardioarrhythmology. Physical and surgical intervention]. PMID- 1894127 TI - [From polemics to a controversy. Coronary risk factors]. PMID- 1894126 TI - [Heart rate adjustment of ST segment depression: a good idea, but what results?]. AB - Since 1977, 30 original reports have been published regarding the heart rate adjustment of the ST segment depression. The aim of the investigators was to find a new criterion more sensitive and more specific than the conventional slope and depression of the ST segment. This is a well known index of ischaemia and it was expected to become more sensitive if adjusted with an index of oxygen demand (the heart rate). In order to have a historical perspective of the debate, all published reports on the ST segment heart rate adjustment were analyzed. The group of Leeds showed no overlap of values between patients without coronary artery disease and patients with one, two, and three vessel disease. The new method, called ST/HR slope, purported to predict the exact number of coronary arteries with critical stenoses. These results have never been duplicated in any other center with the same accuracy. Several authors determined the clinical usefulness of this method and obtained conflicting results. Even now a unanimous agreement has not been reached and the routine utilization of the method in exercise laboratories is still uncommon. From this controversy, it should be learned that a physiological rationale does not always correspond to a relevant clinical result. Only clinical practice can define the real value of a new instrument. PMID- 1894128 TI - [Prognostic significance of a tracing in signal averaging]. PMID- 1894129 TI - [Vittorio Puddu, 1909-1991]. PMID- 1894130 TI - Non-isotonic aerosol challenge in the evaluation of bronchial hyperresponsiveness. PMID- 1894131 TI - International trends in asthma mortality. PMID- 1894132 TI - Sinusitis--present state of the art. PMID- 1894133 TI - Air pollutants. PMID- 1894134 TI - Asthma mortality in a metropolitan county hospital, a 38-year study. AB - A 38-year (1949-1986) retrospective chart review of 535 decedent asthmatic patients was undertaken to determine trends in asthma-related deaths. Records of 187 decedents with clinical and autopsy evidence were analyzed. An overall decrease in asthma-related deaths over the four interval periods of the study was noted. Thirty-five percent of the patients died within 24 hours, and 85% died within 7 days of admission. Seventy-five percent of decedents were greater than 40 years of age. Fifty-two percent of the patients were white, 34% black, and 13% Hispanic. Mortality was higher in younger (less than 40 years) blacks and in older (greater than 40 years) whites. The number of deaths was inversely proportional to the number of patients managed in the pulmonary/ICU setting. Longer duration (greater than 10 years) of asthma was associated with a higher (60%) mortality. Mucus plugging occurred in 74% of patients. Previous hospitalization (93%), previous intubations, and inadequate assessment (peak expiratory flow rates, pulsus paradoxus) also were associated with higher mortality. PMID- 1894136 TI - Is it time for a confederation? PMID- 1894135 TI - Cord blood T-cell determination: a further useful parameter for atopy screening of the newborn? AB - In a prospective study, the total CB IgE and T-cell subpopulations in cord blood of 200 newborn children were determined by means of monoclonal antibodies (CD3, CD4, and CD8). There is no correlation between raised cord blood IgE and reduced T-cell ratio in the cord blood or with a positive family history. In a follow-up study carried out at the age of 12 to 14 months, 21% of atopic children had a positive family history and, simultaneously, a reduced total cord blood T-cell rate (CD3). Only 3% of nonatopic children had a positive family history and a reduced cord blood CD3 ratio. Statistically speaking, this distinction is significant (p less than 0.01). PMID- 1894137 TI - Galen on respiration. PMID- 1894138 TI - Huang-Ti, the Yellow Emperor and the Nei Ching: antiquity's earliest reference to asthma. PMID- 1894139 TI - Landmark commentary: The lymphocytologists; Abell and Schenck on anaphylaxis. PMID- 1894140 TI - Microscopic observations on the behavior of living blood vessels of the rabbit during the reaction of anaphylaxis. 1938. PMID- 1894141 TI - Preclinical markers in studies of Parkinson's disease. AB - The development of reliable preclinical detection procedures for idiopathic Parkinson's disease may be the fundamental advance required for the establishment of the cause, the natural history, and ultimately, the prevention of this neurodegenerative disorder. The usefulness of these preclinical markers in efforts to better understand the etiology and development of this disorder will relate to whether they are direct measures of dopamine production or indirect measures such as metabolic changes or comorbidity, whether they can be used in the first or later decades of life, whether they are invasive, and whether they are expensive and sophisticated or simple and cheap. An overview of the criteria for evaluation of the utility of specific markers, as well as an assessment of the importance of early markers in future research, is presented. PMID- 1894142 TI - Electrophysiologic analysis of early Parkinson's disease. AB - We have been interested in the application of quantitative measures of motor performance as a possible means of early detection of Parkinson's disease. To assess motor function, we have measured movement time (the physiologic correlate of bradykinesia) and reaction time (simple and directional choice) with an upper limb motor task, and tremor with accelerometry and electromyographic recordings. In this report we describe preliminary data from a Parkinson's disease patient group with symptoms of fewer than 2 years' average duration (compared with an age and gender-matched normal control group) which indicate that precise, quantitative tests of motor function can detect the slight deviations from normal that are present in early Parkinson's disease. It appears that tests of bradykinesia are most sensitive, and detection of rest tremor is most specific. These tests may be applicable in screening individuals who are suspected of having or are "at risk for" Parkinson's disease and other related disorders. PMID- 1894143 TI - Long-latency neurodegenerative disease in the western Pacific. AB - The western Pacific parkinsonism-dementia and amyotrophic lateral sclerosis complex is a prototypical neurodegenerative disorder found among inhabitants of Guam, New Guinea (Irian Jaya, Indonesia) and Japan (Kii Peninsula, Honshu). Nonviral environmental factors peculiar to the affected populations seem to play a prominent etiologic role. Although cause-effect relationships cannot be established by epidemiologic studies alone, we have shown in all three affected population groups that individuals develop the amyotrophic lateral sclerosis variant of this disorder after heavy exposure to the raw or incompletely detoxified seed of neurotoxic cycad plants. Since long periods may elapse between cycad exposure and the appearance of neurological disease in humans, cycads may harbor a "slow toxin" that causes the postmitotic neuron to undergo slow irreversible degeneration. Two cycad neurotoxins are recognized, one of which (cycasin) is known to have long-latency effects (tumorigenesis) on mitotic neurons and replicating cells in other tissues. This paper explores the possible relationship between tumorigenesis and long-latency neurotoxicity, and discusses possible biologic markers of cycad exposure and subclinical neurodegenerative disease. PMID- 1894144 TI - Preclinical detection of motor and nonmotor manifestations. AB - The advent of possible protective therapies for Parkinson's disease has created a need for methods of diagnosing the disease before the clinical features become fully evident. As a number of motor and nonmotor manifestations of the disease emerge months to years before a diagnosis can be made, a battery of clinical tests might be sufficient to identify individuals at an earlier stage than is currently possible using the standard history and physical examination. A list of questions regarding possible risk factors, specific symptoms, and observations of family members could be combined in a self-administered questionnaire that might identify individuals with a high probability of early, but otherwise undiagnosable, Parkinson's disease. Identification of subtle motor features is another possible screening method. For example, handwriting and speech are commonly affected prior to diagnosis; thus, automated analysis of these motor actions might also provide detection of incipient disease. PMID- 1894146 TI - Preclinical detection of Parkinson's disease. The next frontier: presymptomatic detection. Introduction. PMID- 1894145 TI - Olfactory dysfunction in three neurodegenerative diseases. AB - Olfactory dysfunction is among the first signs of Alzheimer's disease (AD), idiopathic Parkinson's disease (PD), and the parkinsonism-dementia complex (PDC) of Guam. We have recently demonstrated that the odor identification and detection deficits of patients with PD are equivalent to those of patients with mild AD when subtle differences in cognitive function are statistically controlled for by analysis of covariance. In contrast, patients with progressive supranuclear palsy (PSP) and patients with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced parkinsonism evidence olfactory function much more similar to that of normal controls. In the present study, we administered the University of Pennsylvania Smell Identification Test and the Picture Identification Test to 24 patients with early signs of the PDC of Guam and statistically compared their test scores to those of 24 early-stage AD and 24 early-stage PD patients of similar age and gender from the United States mainland. Although the PDC group evidenced slightly more difficulty in identifying pictures than did the other 2 groups, the odor identification deficit associated with this disorder was of the same magnitude as that observed in AD and PD, suggesting that olfactory testing cannot be used to distinguish among these 3 diseases and that the olfactory dysfunction of these disorders may reflect a common neurologic substrate. PMID- 1894147 TI - Genetic susceptibility to Parkinson's disease. AB - Genetic factors clearly cause Lewy-body Parkinson's disease (PD) in a subset of autosomal-dominant families. However, most cases of PD are sporadic. The two most likely models of four discussed for sporadic PD are the reduced penetrance model and the multifactorial model. Sporadic PD is likely to be caused by the combined effect of environmental precipitating factors and genetic susceptibility factors. Because the number of major genetic factors is likely to be small, these hypotheses can be tested and genetic factors located using linkage mapping techniques. The affected pair analysis methods are especially suited to PD. Finding the genetic susceptibility factors for PD is important because this may be the fastest way to identify the environmental precipitating factors and because it may lead to prevention of PD. Because of the usefulness of identifying genetic susceptibility factors for PD, we are carrying out linkage studies in a group of 16 large autosomal-dominant families with PD and more than 300 living affected PD pairs. PMID- 1894148 TI - Liver enzyme abnormalities in Parkinson's disease. AB - If toxicant exposure contributes to the cause of Parkinson's disease, poor function of detoxifying enzymes could increase vulnerability for Parkinson's disease. Although no hepatic enzyme system has been shown universally to be dysfunctional in Parkinson's disease patients, several have been suggested to be dysfunctional in subgroups, such as those with young age at disease onset. Specific enzymes implicated include several P450 enzymes, most notably P450 IID6, and cysteine dioxygenase. If hepatic enzyme abnormalities contribute to the development of Parkinson's disease, molecular genetic techniques may allow the development of screening tests to identify at-risk subjects in order to intervene with protective therapies. PMID- 1894149 TI - Does a long preclinical period occur in Parkinson's disease? PMID- 1894150 TI - Urban/rural differences in home health patients and services. AB - Using data from the Wisconsin Annual Survey of Home Health Agencies, we describe urban/rural differences for home health care patients. Our findings indicate that urban dwellers are more likely to be home health patients than are rural residents. Urban home health patients are more apt to be nonelderly, male, and have "other conditions" as their primary diagnosis. They are also likely to be more physically dependent and to receive home care longer. Urban home health patients are more typical of long-term care patients, whereas rural patients may be better described as recipients of postacute care, often recovering from diabetes and heart attacks. Possible problems with rural access to home health care are discussed. PMID- 1894151 TI - Caregiving daughters' perceptions of their own and their mothers' personalities. AB - This research explores differences between caregiving daughters' perceptions of their own and their mothers' personalities. A sample of caregiving daughters (N = 150) rated themselves and their mothers on the same 17 personality attributes. Daughters generally rated their mothers more negatively than themselves. Within this pattern of generally negative evaluations, varying types of impairment function differently. Functional impairment is not related to assessments of mothers' personalities, whereas psychological and cognitive impairments are. PMID- 1894152 TI - Finding meaning: an alternative paradigm for Alzheimer's disease family caregivers. AB - Theoretical formulations of stress and coping, family systems, crisis intervention, and loss and grief have inadequately explained how persons might grow and find meaning through their caregiving experiences. An existential theoretical framework guided the data interpretation in a qualitative study of 94 dementia family caregivers. Results suggest that an existential framework provides an alternative paradigm for understanding the caregiving experience. PMID- 1894153 TI - Informal support from black churches and the well-being of elderly blacks. AB - This paper explores the type of support black churches and families provide, and how that support relates to the well-being of elderly blacks. Findings indicate that the family network is perceived as more supportive than the church network, but that church support contributes to feelings of well-being. Perceptions of support from the churches and not the spiritual aspects of religion or involvement in organized religious activities were associated with well-being. PMID- 1894154 TI - Racial differences in the determinants of living arrangements of widowed and divorced elderly women. AB - Ability to afford single, separate households has been perceived as the key determinant of living alone among single older women. This paper shows that, when race is analyzed separately, family-related variables such as marital history and the number of children raised, rather than economic affordability, are the most important factors in the living arrangement decision of widowed elderly women of color. Economic affordability also turns out to be insignificant when white and nonwhite divorced elderly women are analyzed separately. PMID- 1894156 TI - Elders' nonadherence: its assessment and medication reminding by voice mail. AB - This study investigates four questions related to the problem of medication nonadherence among elders. First, does memory failure play a significant role in nonadherence? Second, can memory-related nonadherence be predicted by simple tests of cognitive performance? Third, can the new portable bar code scanner technology be used to unobtrusively monitor nonadherence? Most importantly, can inexpensive telephone voice mail technology be used to improve medication adherence? The results show that: elders have substantial levels of forgetting; nonadherence decreases with higher cognitive test scores; portable bar code scanners are useful for monitoring adherence; and voice mail reduces tardiness and complete forgetting. PMID- 1894155 TI - Elderly support and intergenerational transfer in Zimbabwe: an analysis by gender, marital status, and place of residence. AB - This paper describes elderly support and intergenerational transfer by gender, marital status, and place of residence for 150 elderly persons in Zimbabwe. The survey was conducted in September 1988, and includes information on background characteristics, income, and cash support from all sources, noncash support, and the support of elders to others. Conclusions and implications are discussed. PMID- 1894157 TI - Perceptions of problems associated with aging: comparisons among four older age cohorts. AB - This research examines how the perceptions of aging and the concern over special problems faced by the aged vary among four age cohorts: the middle aged (55-64), the young old (65-74), the old (75-84), and the oldest old (85+). We hypothesized that the middle-aged cohort and the oldest-old cohort would be most pessimistic. The results support the hypothesis for the middle-aged group, but the oldest old were surprisingly optimistic in their view of aging. However, these perceptions by the oldest old cohort are more likely than the others' attitudes to depend on this group's assessment of their own personal problems. PMID- 1894158 TI - Effects of acute and long-term exercise on self-efficacy responses in sedentary, middle-aged males and females. AB - We examined the effects of acute and long-term exercise on perceptions of personal efficacy in sedentary, middle-aged males and females. Both males and females demonstrated significant increases in efficacy following acute exercise. Females, who had demonstrated initially lower self-perceptions than males, made dramatic increases in efficacy during the exercise program, equaling or surpassing those of males. Exploratory analyses revealed significant relationships between self-efficacy and subsequent physiological responses to exercise. PMID- 1894159 TI - Referral outcomes from a community-based preventive health care program for elderly people. AB - The purpose of this study was to determine referral outcomes in a community based, preventive health program for low-income elderly people in California. We examined the records of 2,750 clients who participated in a complete screening exam and who accepted at least one referral. Twenty-four percent of the participants had received a new diagnosis, a new medication, a change in medication dose, a biopsy, or surgery. These results are encouraging for screening clinics focused on low-income seniors. PMID- 1894160 TI - Mental health services for the rural elderly: the SAGE experience. AB - The mental health services of the Senior Adult Growth and Enrichment (SAGE) Program, a demonstration project in North Carolina, are described. The SAGE staff used a differentiated model of day treatment that tracked clients according to disabilities and potentials. Staff provided outreach in a rural area to older people with mental illness and to their caregivers. The rationale and specialized methods of the project are described. Services were tailored to meet unique needs brought on by diverse mental disorders, functional disabilities, and varying life circumstances. PMID- 1894161 TI - Enhancing mutual respect among nursing assistants, residents, and residents' families. AB - Interviews with nursing assistants and residents revealed ways in which they experience respect, disrespect, attachment, and distancing in their relationships with each other. As a result of these findings, an inservice session on interpersonal respect was developed for nursing assistants. Manifestations of disrespect and strategies for promoting mutually respectful relationships among residents, their families, and staff in the facility are presented. PMID- 1894162 TI - Integrating the community into geriatric case management: public health interventions. AB - Gatekeepers, or nontraditional referral sources, have proven to be an effective means of case finding and outreach for the mental health needs of isolated senior citizens. A two-year project administered by the Public Health Division of the Health Services Department in a San Francisco Bay Area county found the gatekeeper concept to be an effective means of case finding in the public health setting. Program statistics showed similar profiles of individuals referred by gatekeepers and other referral sources except that gatekeepers referred more individuals living alone. PMID- 1894163 TI - Two arguments against euthanasia. PMID- 1894164 TI - Lung injury and complement activation: role of neutrophils and xanthine oxidase. AB - Evidence is presented that oxygen products generated from xanthine oxidase (XO) may also be involved in the pathogenesis of neutrophil-mediate lung injury following intravascular activation of complement with cobra venom factor (CVF). CVF injection in rats resulted in a rapid increase in plasma of both XO activity (but not xanthine dehydrogenase) and its reaction product, uric acid. These changes were greatly attenuated in allopurinol-treated animals. The appearance of XO activity was paralleled by a rise in plasma of histamine. Prevention of histamine release by pretreatment of rats with cromolyn abolished both the rise in plasma histamine and the increase in XO activity. Since we have previously shown that histamine can enhance XO activity in vitro and in vivo (Am. J. Pathol. 135:203, 1989), these observations suggest that the increase in plasma XO activity following CVF injection is related to the appearance in plasma of histamine. Accordingly, pretreatment of rats with xanthine oxidase inhibitors (allopurinol, lodoxamide) or prevention of histamine release by pretreatment with cromolyn significantly attenuated development of lung injury following injection of CVF. Our data support the concept that oxygen radicals derived from both neutrophils and XO are playing a role in the CVF-induced acute lung injury. PMID- 1894165 TI - Characterization of products formed during the autoxidation of beta-carotene. AB - The anticarcinogenic action of carotenoids such as beta-carotene has been frequently ascribed to their antioxidant properties. However, very little is actually known about the nature of the antioxidant reaction or the products that are formed. beta-Carotene was exposed to either spontaneous autoxidation conditions or to radical-initiated autoxidation conditions. The products were separated by reverse-phase HPLC, and individual peaks were characterized with an on-line diode array detector. Carbonyl products were isolated and characterized by several procedures, including borohydride reduction to the corresponding alcohols, derivatization with O-ethyl-hydroxylamine to the corresponding O-ethyl oximes of the carbonyls, and analysis by GC-MS. Under the conditions of the experiments, the formation of a homologous series of carbonyl products was demonstrated, including beta-apo-13-carotenone, retinal, beta-apo-14'-carotenal, beta-apo-12'-carotenal, and beta-apo-10'-carotenal. Several very hydrophobic compounds were formed, which have not been previously identified. In addition, the products of NaOCl-treatment of beta-carotene were analyzed, and shown to be significantly different from the autoxidation products. This type of product analysis should be useful in determining the nature of the oxidants reacting with beta-carotene in vivo. PMID- 1894166 TI - The lipid peroxidation theory of lipofuscinogenesis cannot yet be confirmed. PMID- 1894167 TI - Chronic constipation following simple hysterectomy is rare. PMID- 1894168 TI - Manometric characterization of rectal dysfunction following radical hysterectomy. AB - Bladder dysfunction thought to be due to partial denervation has been described following radical hysterectomy. Some patients experience acute and chronic rectal dysfunction characterized by difficulty with defecation and loss of defecatory urge. To define this abnormality, anorectal pressure profiles were examined in 15 patients with Stage I carcinoma of the cervix before and after radical hysterectomy. Profiles were done using standard anorectal manometry with a water infused system. In all patients preoperative manometric profiles were normal; postoperative studies were abnormal in all patients. Features seen include altered relaxation of the internal sphincter, increased distension needed to trigger relaxation, and decreased rectal sensation; external sphincters and resting internal sphincters were unchanged. Postoperatively, 12 patients reported problems with rectal function. A physiologic defect is definable in patients undergoing radical hysterectomy; this suggests disruption of the spinal reflex arcs controlling rectal emptying. These physiologic abnormalities correlate with the clinical symptomatology experienced by some patients. Continuing definition and evaluation of management options in this situation should be useful in developing effective therapy for rectal dysfunction following radical hysterectomy. PMID- 1894169 TI - Oncogenic potential of tamoxifen on endometria of postmenopausal women with breast cancer--preliminary report. AB - Tamoxifen (TAM), a nonsteroidal antiestrogen, is used for pre- and postmenopausal patients with breast cancer. Recent reports suggest that TAM may cause endometrial neoplasia. This study is designed to evaluate the oncogenic potential of low-dose TAM on the endometrium. Initially, endometrial screening of patients with breast cancer who had received TAM therapy for at least 12 months was conducted. Seventy patients were interviewed and office endometrial biopsies were obtained from thirty-eight patients. Seven (18%) had hyperplastic changes, ranging from simple hyperplasia through complex hyperplasia with atypia. The following prospective study was conducted: after breast surgery and prior to initiation of TAM therapy, an office endometrial sampling was obtained as a control. After initiation of TAM therapy, biopsies were repeated every 4 to 6 months as long as the patients remained asymptomatic. Nineteen patients were interviewed. Twelve patients were biopsied and followed from 3 to 15 months. One patient refused additional biopsies. Eleven patients had repeat biopsies after initiation of TAM. New hyperplastic changes were found in 3/11 (27%) patients. The preliminary results of this study (although with a small number of patients) indicate that TAM may have some neoplastic effect on the endometrium of postmenopausal patients with breast cancer. This study is still in progress. Additional prospective studies are warranted before a significant correlation between TAM and endometrial neoplasia is confirmed. PMID- 1894170 TI - Retroperitoneal lymphatic involvement with epithelial ovarian tumors of low malignant potential. AB - A comprehensive understanding of retroperitoneal lymphatic involvement is lacking in tumors of low malignant potential. This study was undertaken to evaluate retroperitoneal lymphatic involvement in patients with ovarian tumors of low malignant potential. One hundred seventy-one patients were diagnosed with epithelial ovarian tumors of low malignant potential between 1979 and 1989. Thirty-four (20%) of these patients underwent surgical staging which included lymph node sampling. The stage distribution was Stage I in 17 patients (50%), Stage II in 4 patients (12%), and Stage III in 13 patients (38%). The histology of the tumors was serous in 26 patients (76%), mucinous in 7 patients (21%), and seromucinous in 1 patient (3%). The incidence of retroperitoneal lymphatic involvement was 21%. The occurrence of positive pelvic and para-aortic nodes was 17 and 18%, respectively. Patients with localized intraperitoneal disease were upstaged in 22% of the cases based on retroperitoneal lymphatic involvement. Four of twenty-one patients (19%) with intraperitoneal disease confined to the ovary and two of six patients (33%) with intraperitoneal disease confined to the pelvis were upstaged to Stage III as a result of retroperitoneal lymphatic disease. Although the nodal status of patients did not significantly affect survival, those patients with localized intraperitoneal disease and nodal involvement had a higher incidence of recurrence which was statistically significant (P = 0.025). Accordingly, retroperitoneal lymph node sampling at the time of initial laparotomy may provide valuable prognostic information regarding recurrence in patients with tumors of low malignant potential. PMID- 1894171 TI - Invasive vaginal carcinoma: analysis of early-stage disease. AB - From 1960 through 1987, 89 patients with stage I (44 patients) or II (45 patients) vaginal carcinoma (excluding melanomas) were treated primarily at the Mayo Clinic. Treatment consisted of surgery alone in 52 patients, surgery plus radiation in 14, and radiation alone in 23. The median duration of follow-up was 4.4 years. The 5-year survival (Kaplan-Meier method) was 82% for patients with stage I disease and 53% for those with stage II disease (p = 0.009). Analysis of survival according to treatment did not show statistically significant differences. This report is consistent with previous studies showing that stage is an important prognostic factor and that treatment can be individualized, including surgical treatment for primary early-stage vaginal cancer. PMID- 1894172 TI - Prognostic factors for recurrence following negative second-look laparotomy in ovarian cancer patients treated with platinum-based chemotherapy. AB - Prior studies of the risk of recurrence following negative second-look laparotomy have included patients treated with a variety of chemotherapeutic regimens, including nonplatinum regimens. We have examined the long-term outcome and risk factors for recurrence among a homogeneous group of platinum-treated patients. During the years 1978-1987, 91 patients at Memorial Sloan-Kettering Cancer Center had a negative second-look laparotomy following platinum-based chemotherapy for epithelial ovarian cancer. The mean age at diagnosis was 57 years, with a range of 30 to 79. Distribution by stage was as follows: I, 10; II, 18; III, 57; IV, 6. The mean number of cycles of platinum prior to second-look surgery was 6.3. The mean number of biopsies taken at negative second-look laparotomy was 12. Lymph node biopsies were done in 47/91 (52%) of patients. Median follow-up from the date of second-look laparotomy was 54.6 months among survivors. Forty of ninety one patients (44%) have had recurrence, almost 40% of which were outside the peritoneal cavity. The mean interval from negative second-look laparotomy to recurrence was 24 months (range, 2-70 months). By multivariate analysis the risk of recurrence was significantly related to stage (P = 0.017), histologic grade (P = 0.041), and the amount of tumor remaining after the first operation for ovarian cancer (P = 0.015). Recurrence by stage was as follows: stage I, 1/10 (10%); stage II, 5/18 (28%); stage III, 31/57 (54%); stage IV, 3/6 (50%). Recurrence by grade was as follows: grade 1, 4/18 (22%); grade 2, 11/28 (39%); grade 3, 25/45 (56%). There was no relationship between the risk of recurrence and the number of cycles of platinum, the number of biopsies performed at second-look, or the number of months from primary surgery to second-look. Patients having negative second-look laparotomy following platinum-based chemotherapy for advanced epithelial ovarian cancer have a substantial risk of recurrence, particularly within the first 3 years. Such patients should be offered participation in clinical trials of consolidation therapy directed against both intraperitoneal and extraperitoneal disease. PMID- 1894173 TI - Lymphvascular space involvement--a prognostic indicator in endometrial adenocarcinoma. AB - The present study evaluates the effects of various prognostic indicators on survival of patients with clinical Stage I endometrial carcinoma. Ninety-three patients who were treated for clinical Stage I endometrial adenocarcinoma at Maimonides Medical Center from October 1979 to October 1987 had sufficient surgical-pathological information for retrospective surgical staging according to the new FIGO classification. Histology was reviewed. A new grade and surgical stage was assigned to each patient in accordance with the recent FIGO guidelines for surgical staging of corpus cancer. Poor prognostic indicators, namely, tumor grade, depth of myometrial invasion, peritoneal cytology, lymph node metastases, and lymphvascular space (LVS) involvement, were correlated with 5-year survival rates. Survival rates were calculated by the life table method. Depth of myometrial invasion, lymph node involvement, and peritoneal cytology had significant statistical correlation with poor survival. Positive finding of each of the prognostic indicators, including LVS involvement, was significantly associated with poor survival (all P less than 0.001). The value of these prognostic indicators in early endometrial carcinoma is discussed. PMID- 1894174 TI - Neoadjuvant chemotherapy and interval debulking for advanced epithelial ovarian cancer. AB - A retrospective matched-control study was conducted to review our experience with FIGO stage III and IV epithelial ovarian cancer in patients referred after initial laparotomy and biopsy only. The study group comprised 22 patients; planned treatment was two to four cycles of chemotherapy, interval debulking surgery, six more chemotherapy cycles, and second-look laparotomy. Two control groups were matched with the study group according to FIGO stage, histologic type, and grade (2 or 3) and patient age +/- 5 years. The first control group (22 patients) had greater than 2 cm residual disease after initial surgery; their planned treatment was a minimum of six cycles of chemotherapy plus second-look laparotomy. The second control group (18 patients) was referred after initial laparotomy and biopsy only; their disease was immediately reexplored and debulked. Subsequent planned treatment was a minimum of six cycles of chemotherapy plus second-look laparotomy. All patients received cisplatin-based chemotherapy. Optimal cytoreduction to less than or equal to 2 cm was achieved for 77% of the study group vs 39% of the immediate-reexploration group (P = 0.02). Median survival times for the three groups were not different (16 vs 19.3 vs 18 months, respectively) (P = 0.58). Within the study group, patients who were optimally debulked survived significantly longer than those who were not (18.1 vs 7.5 months) (P = 0.02). Morbidity of the interval debulking procedure was acceptable. Study findings suggest that patients with bulky residual disease have a uniformly poor prognosis regardless of the timing of further surgery. PMID- 1894176 TI - Cisplatin-based combination chemotherapy in carcinoma of the fallopian tube. AB - Forty-three cases of primary tubal adenocarcinoma were treated at Memorial Sloan Kettering Cancer Center between 1979 and 1989. Thirty-eight patients who received cisplatin-based combination chemotherapy following primary surgery were reviewed. The mean patient age was 59 years, with 86% postmenopausal. Distribution by stage was as follows: I, 3 (7%); II, 4 (11%); III, 27 (71%); and IV, 4 (11%). Median follow-up from the time of diagnosis was 62 months (range, 5-132). Overall survival for all 38 patients by Kaplan-Meier analysis was 51% at 5 years. Excluding stage I, patients with no residual disease following surgery had a significantly higher 5-year survival (83%) than those left with gross residual disease (28%). Twenty-six patients underwent a second-look procedure. Of the 21 patients with advanced (stages III, IV) disease undergoing reexploration, 11 (52%) had a negative second-look and 10 (48%) were positive. Ten of the eleven patients with a negative second-look remain clinically free of disease with a median follow-up of 49 months. One patient with stage III disease had recurred after 47 months. Carcinoma of the fallopian tube appears to respond favorably to cisplatin-based multiagent chemotherapy. Patients with advanced-stage disease who achieve a negative second-look appear to have an improved possibility of remaining disease-free over similar-stage patients with ovarian cancer. PMID- 1894175 TI - Reverse hysterocolposigmoidectomy (RHCS) for resection of panpelvic tumors. AB - Lateral retroperitoneal approaches to abdominopelvic masses are commonly employed; the reverse hysterocolposigmoidectomy (RCHS) in addition utilizes transabdominal entry of the vaginal and rectovaginal spaces to provide medial access to the uterosacral and cardinal ligaments as well expose a tumor-free segment of the rectosigmoid for en bloc resection of panpelvic tumors. Thirty-one patients underwent reverse hysterocolpectomy for extensive, symptomatic pelvic malignancies. All patients had complete resection of pelvic tumor, and there were no perioperative deaths. Sigmoid resection was required in 25 patients with 22 primary reanastomosis and 3 end colostomies performed. In 6 patients, vaginal entry facilitated tumor resection while sparing the rectosigmoid. Average operative blood loss was 2677 cc. Early postoperative morbidity (1-30 days) occurred in 13 patients; febrile morbidity (6 patients) was the common complication. Late morbidity (1-6 months) was seen in 10 patients, including 1 fatal pulmonary embolism at 5 months. Subsequent therapy was tolerated well. Mean survival/follow-up is 15.7 months (range, 1 to 49 months). Seventeen patients are alive, seven patients without evidence of disease (average 13.4 months), and ten patients are alive with disease (average follow-up, 28.3 months). Thirteen patients are dead of disease or complication (average survival, 13.7 months). We conclude that RHCS facilitates resection of extensive pelvic tumors with acceptable morbidity. PMID- 1894177 TI - [Prevention and diagnosis of postoperative hemorrhage]. PMID- 1894178 TI - [Differential diagnosis of acute pelvic pain]. PMID- 1894179 TI - [Acute diagnosis and therapy in hypertensive emergencies, pre-eclampsia and eclampsia]. PMID- 1894180 TI - [Fever at delivery]. PMID- 1894181 TI - [Acute abdominal pain in pregnancy--incidence and differential diagnosis]. PMID- 1894182 TI - [Hemorrhage after delivery of the infant]. PMID- 1894183 TI - [Prolapse of the amniotic membranes--indications for total cervical cerclage?]. PMID- 1894184 TI - [Antepartum cardiotocogram]. PMID- 1894185 TI - The effects of recombinant hirudin on various platelet functions. AB - The effect of two recombinant hirudins, HBW 023 (Hoechst AG, Frankfurt, FRG) and CGP 39393 [recy(tyr 63)] (Ciba Geigy, Basel, Switzerland) on various platelet functions has been investigated in blood samples of healthy volunteers anticoagulated with hirudin at concentrations of 10, 30, 50 micrograms/ml blood. Spontaneous aggregation was rarely observed in hirudinized platelet-rich plasma (PRP) compared to citrate-PRP. In comparison with citrate-PRP, both hirudins reduced the maximal response to epinephrine, but had no influence on the maximal response to ADP. Both hirudins reduced platelet adhesion to siliconized glass and inhibited platelet spreading compared to citrate-PRP. If hirudin was added to citrate-PRP, platelet count, epinephrine-induced aggregation, platelet spreading and adhesion remained unchanged while the maximal response to ADP increased. If citrate was added to hirudin-PRP, the maximal response to epinephrine as well as platelet spreading and adhesion increased to the extent observed in citrate-PRP. The effects of hirudin on platelet function are more pronounced than those of unfractionated heparin. PMID- 1894186 TI - Past, present and future of hirudin. AB - The naturally occurring anticoagulant from medicinal leeches, hirudin, which we isolated and biochemically analyzed 30 years ago as a miniprotein with specific antithrombin activity, has afterwards been employed for scientific and diagnostic purposes in hematology. Pure hirudin proved to be an antithrombotic agent of high quality that displays an antithrombotic action dependent upon its blood level. After intravenous injection, it is distributed in the extracellular space and is almost completely eliminated through the kidneys by glomerular filtration in a biologically active form. The efficacy of hirudin in preventing venous and arterial thrombosis and disseminated intravascular coagulation was demonstrated in various animal models. Clinical pharmacological studies corroborated the specific pharmacodynamic and pharmacokinetic properties of hirudin found in animal experiments. Genetic engineering led to the availability of sufficient quantities of recombinant hirudin (r-hirudin) for clinical purposes. Pharmacologic profiling of r-hirudin showed that both its pharmacokinetic and pharmacodynamic characteristics are very similar to those of native hirudin. Clinical pharmacological studies with r-hirudin revealed that, at single therapeutically relevant doses, r-hirudin is a well-tolerated and potent anticoagulant without any detectable side effects and allergic reactions. Further preclinical studies of r-hirudin should concentrate on identifying possible indications for use, on the development of r-hirudin preparations and derivatives, and on the development of antidotes for hirudin. PMID- 1894187 TI - Effect of recombinant hirudin on cytosolic Ca2+ concentrations using different platelet stimulators. AB - Cytosolic Ca2+ concentration, [Ca2+]i, and aggregation behavior of hirudinized platelet suspensions were examined under stimulation with thrombin, adenosine diphosphate, platelet-activating factor, collagen and the calcium ionophore, ionomycin. A rise in [Ca2+]i, a key step in platelet activation, was only inhibited by recombinant hirudin r-hirudin using the agonist thrombin. All other stimulators including ionomycin were not affected by r-hirudin. If hirudinized blood was gel-filtered before platelet stimulation, thrombin induced the same response as citrated platelet suspensions. Aggregation studies and calcium influx using various stimulators showed good correlation: only thrombin-induced aggregation was completely inhibited by r-hirudin. These results support the hypothesis that hirudin inhibits platelet function by thrombin binding and not by direct interaction with platelets. PMID- 1894188 TI - Clinical pharmacology of recombinant hirudin. AB - Pharmacological profiling of recombinant hirudin (r-hirudin) has shown that this selective tight-binding thrombin inhibitor is a potent, well-tolerated anticoagulant. Clinical pharmacological studies were performed in human volunteers after single and repeated doses of 0.1-0.5 mg/kg. Generally, administration of r-hirudin was tolerated without side effects. Thrombin time and partial thromboplastin time were prolonged dependent on the r-hirudin level in plasma. Platelet counts, fibrinogen level and fibrinolytic system remained unchanged. Bleeding time was not prolonged. On intravenous injection, r-hirudin was rapidly distributed into the extracellular space and eliminated, with a dose dependent half-life of 1-2 h (first-order kinetics). After subcutaneous administration, the rH level in blood reached plateau values within 60-120 min. The high recovery of unchanged r-hirudin in the urine identified renal excretion as the predominant route of r-hirudin clearance. PMID- 1894189 TI - Hirudin in disseminated intravascular coagulation. AB - Various reactions of disseminated intravascular coagulation (DIC) were experimentally induced by infusion of thrombokinase in rats, by administration of endotoxin in rabbits and pigs and by infusion of adrenaline and thrombin in dogs. Low plasma concentrations of recombinant hirudin (r-hirudin; 20-200 ng/ml) were sufficient for the inhibition of the different triggering mechanisms. The studies on the pharmacological profile of r-hirudin in DIC therapy confirm the efficacy of this specific tight-binding thrombin inhibitor. PMID- 1894190 TI - Hirudin as anticoagulant in experimental hemodialysis. AB - After genetically engineered recombinant DNA desulfatohirudin (r-hirudin) had been investigated as to its pharmacokinetic behavior and blood level course in nephrectomized dogs, the compound was studied for its capability to prevent thrombus formation in the extracorporeal circulation. Beagle dogs underwent bilateral functional nephrectomy followed by experimental hemodialysis. r-Hirudin content in blood, fibrinogen level as well as platelet count were determined before and during the dialysis. Furthermore, the blood loss during the experiment was measured as well as the mean arterial pressure and the pressure in the blood line system. Intravenous administration of the thrombin inhibitor resulted in initial distribution in the extracellular space (distribution phase 90 min) followed by retarded decrease of the r-hirudin blood level (t1/2 beta approximately 6-8 h) which is due to the missing renal excretion of the inhibitor. This caused a long-lasting, dose-dependent anticoagulant effect, which is not only characterized by the prevention of increasing pressure before the capillary dialyzer but also by the reduced drop in fibrinogen and platelets during hemodialysis. The required dose of r-hirudin (0.5 mg/kg) is within a range where bleeding complications will not occur yet. PMID- 1894191 TI - Hirudin for diagnostic purposes. AB - Hirudin serves as a versatile tool for the control of thrombin activity in hemostaseology. It may be added in excess to blood, plasma or test mixtures to prevent catalytic and nonenzymatic effects of thrombin. It may be used to quench thrombin activity upon extensive or limited action. Unlike heparin-antithrombin III complex which exclusively inhibits alpha-and gamma-thrombin, hirudin also inhibits meizothrombin, a precursor of alpha-thrombin. Thus, hirudin may be used for the detection of meizothrombin as well as for the prevention of its action in plasma samples. In conjunction with chromogenic substrates, hirudin may serve to discriminate between actions mediated by thrombin, its precursors, cofactors and effectors and actions of other enzyme systems. The principle of this hirudin application is exemplified for factor-V- and factor-VIII-dependent anticoagulant activity of protein C. PMID- 1894192 TI - Recombinant hirudin--initial observations in reconstructive microsurgery. AB - Recent advances in microvascular techniques have significantly enhanced the success rate of these procedures. Microvascular free tissue transfers at present have a 85-90% success rate. This, however, still leaves a 10-15% failure rate due primarily to thrombosis of the blood vessels at the anastomotic site. Previous work in the field has shown that anticoagulants such as heparin can reduce the rate of thrombosis. However, heparin can also cause on-site bleeding. Hirudin, a potent thrombin inhibitor of 65 amino acids, is available through recombinant technology. Our current experimental work utilized 75 male Sprague-Dawley rats for assessing the efficacy of hirudinized saline versus saline alone and heparinized saline as an irrigant in a microsurgery model of anastomosis. After exposing the right femoral artery in a standard fashion, the artery was clamped and a standard transverse division of the vessel was made. The vessel ends were irrigated with one of the three solutions then anastomosed. Vessels were observed for patency over a 3-day period. Initial results showed comparable performance of hirudinized saline and heparized saline, both of which were better than saline, for preventing thrombosis. From these initial data, and the reduced bleeding risk associated with hirudin, this agent appears to be a useful anticoagulant in microsurgery. PMID- 1894193 TI - Thrombin inhibition by hirudin: how hirudin inhibits thrombin. AB - In addition to its classical active-site regions (catalytic site and adjacent regions), alpha-thrombin has a unique anion-binding exosite, which is functionally independent of the catalytic site and is involved in fibrin(ogen) recognition. This exosite also accounts for adhesion to negatively charged surfaces (e.g., glass), binding to cell surfaces, and interactions with the anionic tail of hirudin. Hirudin (as an apolar, tridisulfide-linked core structure followed by its anionic tail) interacts with alpha-thrombin by apolar (e.g., catalytic-site and adjacent regions of thrombin), as well as by ionic binding (e.g., anion-binding exosite). Circular dichroism measurements reveal a sigmoidal nonadditivity for the hirudin tail fragments, which block fibrinogen clotting activity without interfering with tripeptide chromogenic substrate activities. Such fragments, however, inhibit factor V activation to much lesser extents than hirudin, where factor V activation is the key step in regulating thrombin generation by hirudin or heparin/antithrombin III. Hirudin-derived antithrombotics may thus have differential modes of action in hemostasis and wound healing processes. PMID- 1894194 TI - The history of leeching and hirudin. AB - Leeching is an art dating back at least to ancient Egypt. It reached its zenith in the late 18th and early 19th centuries. The antithrombotic quality of leech saliva was first noted by Haycraft in 1884 and the active anticoagulant ingredient isolated in 1904 by Jacoby. He gave this agent the name 'hirudin'. Hirudin was isolated in pure crystalline form by Markwardt in 1957 and first produced in quantity by genetic engineering in 1986. The salivary glands of several species of leech also contain other biologically active substances which are currently undergoing investigation. PMID- 1894195 TI - Effect of hirudin on the chemotactic properties of alpha-thrombin. AB - A study by an agarose technique of the chemotactic power of human alpha-thrombin on polymorphonuclear leukocytes reveals that this enzyme has a chemotactic activity. Hirudin, which inhibits the coagulant properties of thrombin, suppresses these chemotactic properties. This effect could be explained by the binding of hirudin to the structural domain of alpha-thrombin involved in its chemotactic activity. PMID- 1894196 TI - Structure-function and refolding studies of the thrombin-specific inhibitor hirudin. AB - We have developed a novel expression and purification system that yields recombinant desulfo-hirudin (HV-1) with high specific activity (10,000 antithrombin units/mg) and an inhibition constant (Ki) for human alpha-thrombin of 0.2 pM. Reduced and denatured hirudin rapidly refolds to the native, fully active conformation at high concentration (greater than 50 mg/ml) by incubation at pH 10. Analytical gel filtration studies at neutral pH suggest that hirudin is a multimer. Initial binding of hirudin to thrombin appears to be followed by dissociation of the hirudin multimer to give a tight-binding 1:1 hirudin:thrombin complex. Thrombin inhibition studies showed that hirudin synthetic peptide fragments 42-65 and 51-65 [but not (Ala22)-6-28, containing two of the three disulfide bonds formed in native hirudin] were similarly effective in inhibiting thrombin cleavage of fibrinogen (IC50 = 4.9 and 6.0 microM, respectively, at a thrombin concentration of 1 microM). We conclude that hirudin has unusual structural and refolding properties and that its mechanism of inhibition involves noncovalent interaction with multiple sites on thrombin. The interaction of hirudin (specifically the region of Lys-47) with the basic specificity pocket of thrombin may contribute to the binding but is not essential for its inhibitory activity. PMID- 1894197 TI - Laboratory assays for the evaluation of recombinant hirudin. AB - Several laboratory methods are available to measure the anticoagulant activity of recombinant hirudin (r-hirudin), a potent thrombin inhibitor. These assays include clot-based, amidolytic, immunologic and physicochemical techniques. Although r-hirudin, like heparin, is an effective anticoagulant, the mechanism of action of the two agents is different. Thus it is not surprising that the global tests, such as the prothrombin time (PT), partial thromboplastin time (APTT) and the Heptest (Haemachem, Inc., St. Louis, Mo., USA), do not show adequate responses to r-hirudin. In the range of 0.5-10.0 microgram/ml, where full anticoagulation is achieved, as determined by animal models of thrombosis, these assays show little to no prolongation of the time to clot. In order to find a more suitable assay system, modifications of the above assays were evaluated. The diluted APTT and diluted Heptest showed linear concentration-dependent responses to lower levels of r-hirudin with an enhanced sensitivity than that of the classical assays. On the other hand, the diluted thrombin time was too sensitive. Whole-blood clotting assays, ACT and thrombelastograph, effectively measured r hirudin levels up to 25 micrograms/ml. The amidolytic anti-factor IIa assay, specific for evaluating direct thrombin inhibition, was very effective particularly when modified to decrease the sample:thrombin ratio. This assay may be useful in quality control since it is biochemically defined, and reagents are easily standardized. The relevance of the results of the anti-IIa assay to clinical conditions, however, remains to be determined. Thrombin generation assays have limited value in monitoring the anticoagulant effect of r-hirudin since the effect of thrombin inhibition by r-hirudin on coagulation feedback mechanisms, and thus the effect on thrombin generation, appears to be minimal. Immunologic methods such as ELISA and RIA are under development, but they may only be useful for the direct quantitation of absolute levels of r-hirudin and not for monitoring the clinical anticoagulant action. Furthermore, these assays are only sensitive to sub-microgram/ml levels. Therefore, thrombin-based clotting and amidolytic assays may at present be the best choice for evaluating the functional, clinical antithrombotic effects of r-hirudin. PMID- 1894198 TI - Some objective considerations for the neutralization of the anticoagulant actions of recombinant hirudin. AB - Recombinant hirudin (r-hirudin) is currently under development as an anticoagulant for use in surgery, therapeutic anticoagulation, disseminated intravascular coagulation and other pathologic states involving the generation of thrombin. Circulating levels of r-hirudin as an antithrombotic agent range from 2 to 20 micrograms/ml (0.1-1.0 mg/kg) as determined in an animal model of stasis thrombosis. In order to establish a relationship between the r-hirudin circulating level and bleeding, we utilized a rabbit ear blood loss model. r Hirudin did not produce any loss of blood at dosages up to 20 micrograms/ml i.v. (1.0 mg/kg). When the circulating levels were maintained at 20 micrograms/ml for periods of up to 3 h, no increase in blood loss was observed. At 50 and 100 micrograms/ml initial circulating levels (2.5 and 5.0 mg/kg) a dose-dependent increase in the blood loss was observed which was equivalent to that observed with 1.25 and 2.5 mg/kg i.v. heparin. Such levels of r-hirudin are not expected in clinical usage. In contrast to heparin, the anticoagulant actions of r-hirudin were not neutralized by protamine sulfate, platelet factor 4, other polycationic agents and heparinase. In our studies, the blood loss induced by greater than 2.0 mg/kg i.v. dosages of r-hirudin in an animal model was neutralized by the administration of an activated prothrombin complex concentrate at 25 U/kg. In a similar experimental setting, r-factor VIIa was also partially effective. These studies suggest that r-hirudin anticoagulation may not require neutralization, since bleeding effects are not observed at effective antithrombotic dosages in individuals with normal hemostatic status.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1894199 TI - Effects of different hirudins and combinations of low doses of hirudin, heparin and acetylsalicylic acid in a rat microcirculatory thrombosis model. AB - Two recombinant hirudins (r-hirudin), natural hirudin and hirudin in combination with heparin or acetylsalicylic acid (ASA) have been studied in a thrombosis model in which rat mesenteric venules of a diameter of 20-30 microns were injured by well-defined argon laser lesions. In the animal model all hirudins showed significant and dose-dependent antithrombotic effects in doses between 0.05 and 0.1 mg/kg after single intravenous and subcutaneous injections. The antithrombotic effect of single (0.2 mg/kg i.v. or 0.1 mg/kg s.c.) injections lasted longer than 4 h (i.v.) or 6 h (s.c.). Hirudin at a dose of 0.1 mg/kg and heparin at doses of 0.05 mg/kg showed a significant antithrombotic effect 2 h after subcutaneous injection. When heparin and hirudin were injected together at this dosage, the effect of the combination was in the same range as that of unfractionated heparin or hirudin alone. An additive antithrombotic effect was observed if a low dose of r-hirudin (0.1 mg/kg) was combined with a moderate dose of ASA (10 mg/kg). PMID- 1894200 TI - Effect of recombinant hirudin (LU 52369) on reocclusion rates after thrombolysis in rabbits. AB - The effect of recombinant hirudin (r-hirudin, LU 52369) and unfractionated heparin on recombinant tissue-type plasminogen activator (rt-PA; LU 50232) thrombolysis and reocclusion rates after successful thrombolysis was studied in a copper-coil-induced thrombus model in the iliac artery of anesthetized rabbits. Simultaneous administration of rt-PA and recombinant hirudin (r-hirudin) at a dose not affecting the partial thromboplastin time (PTT) increased the number of recanalized arteries significantly. The incidence of reocclusion was drastically reduced from 100% to less than 25%. At a dose increasing PTT twofold, unfractionated heparin had no effect on the incidence of reperfusion and reocclusion. These experimental data indicate that the combination of rt-PA with low-dose r-hirudin may be useful for the prevention of early reocclusion in thrombolytic therapy. PMID- 1894201 TI - Comparative study of three recombinant hirudins with heparin in an experimental venous thrombosis model. AB - Three recombinant hirudins (r-hirudins) produced by genetic processes from Escherichia coli and yeast were studied. r-Hirudins could be an alternative treatment to heparin; so, the antithrombotic activity of these drugs should be compared to heparin, the reference substance, in an experimental venous thrombosis model. In this model, the effect of these r-hirudins on thrombus weight reduction were not identical. They varied depending on the original product (E. coli or yeast). The growth-inhibiting activity of r-hirudins on existing thrombi is not dose dependent, whereas that of heparin is. Moreover, in the conditions of this study, higher doses of heparin, but not of hirudins, increased the bleeding time. Although hirudin has limited applications for the time being, it seems an interesting anticoagulant drug, and the availability of r hirudin opens new therapeutic anticoagulation perspectives. PMID- 1894202 TI - Oregon's response to the health care crisis. PMID- 1894203 TI - National health line. PMID- 1894204 TI - Reflections on the casework relationship: beyond empiricism. AB - This article examines the dynamics of the casework relationship from a holistic perspective. The significance of the interplay between caseworker and client often evades efforts at objective evaluation. Too often emphasis is placed on concrete indications of progress. Staff who look solely at these measures may become frustrated and lose sight of internal change not easily revealed in empirical studies. This article looks at how long-term casework relationships revolve around existential issues that lie at the heart of psychiatric rehabilitation. These relationships, however resistant to stringent measurement, enjoy value apart from specific achievements and merit recognition in their own right. The ordeal of change that both parties endure leaves them heir to a legacy of struggle and renewal. PMID- 1894205 TI - Responding to psychosocial needs: physician perceptions of their referral practices for hospitalized patients. AB - Physicians play a critical gatekeeping function related to psychosocial problem identification and subsequent referral to appropriate hospital or community services. Thirty physicians on staff at a moderate-size, multiservice medical facility were interviewed to determine their perceptions regarding identification of and referral rates for psychosocial problems of their hospitalized patients. In addition to raising questions for further investigation, this article provides a useful structure for gathering data for use by hospital social work departments in developing strategies to enhance physicians' collaboration with hospital social workers. PMID- 1894206 TI - Job satisfaction, burnout, and turnover in health care social workers. AB - The findings of two consecutive surveys of job satisfaction and burnout in national samples of health care social workers are presented. Between 1979 and 1989, there were significant increases in the proportion of social workers employed in private versus public agencies, in quantitative workload, and in social workers' perceptions of the challenges presented by their jobs. Role conflict and role ambiguity, lack of comfort, and dissatisfaction with financial rewards emerged as significant predictors of depersonalization and burnout. However, a significant increase in social workers' feelings of personal accomplishment also occurred, and high challenge emerged as a significant predictor of sense of effectiveness. PMID- 1894207 TI - The social work group and its distinct healing qualities in the health care setting. AB - This article describes how the humanistic values and democratic norms fundamental to social group work are operationalized in groups in the medical setting. The author delineates numerous values and norms and identifies and describes the uses of practice interventions in health care groups. The focus is on group practice that provides a healing environment of caring, empowerment, and support for members. Practitioner efforts center on the development of group norms that enhance belonging in open-ended and closed groups, foster diversity in the group, include rather than exclude others, widen freedom of choice and open decision making, and help members question the authority of the worker as well as of the hospital system. Illustrative examples of group forms are included to demonstrate practice in this framework. PMID- 1894208 TI - Operating a member-employing therapeutic business as part of an alternative mental health center. AB - The promises of deinstitutionalization have not been kept for unemployed chronically mentally ill people. This article describes an innovative community support program--a nonprofit therapeutic member-run business. Rainbow Services provides opportunities for adults with chronic mental health problems to learn marketable job skills and necessary social skills through participation in various work settings. On-site job training, vocational education, socialization, and job counseling are offered. Thirteen years of business success demonstrate that chronically mentally ill people can function productively in the community. The features of the business are related to beliefs and values familiar to early settlement house workers and social activists and support social work's claim to leadership in working with this population. PMID- 1894209 TI - A 20-month olestra feeding study in dogs. AB - Three groups of beagle dogs (five/sex/group) were fed olestra, a mixture of octa , hepta- and hexa-esters of sucrose formed with long-chain fatty acids, at 0, 5 or 10% of the diet for 20 months. The objective of the study was to assess the potential chronic toxicity of olestra in a non-rodent species. The feed was supplemented with vitamins A and E to ensure that the diets were nutritionally adequate and comparable for all groups. The levels of supplementation were established in a 91-day feeding study. Survival was 100% and growth was not affected by olestra. Olestra-fed animals consumed more feed than controls, apparently to compensate for the caloric dilution of the diet by olestra, but the increases were generally not statistically significant. No biologically significant changes were seen in haematological or serum biochemical parameters or in vitamin D and vitamin K status of the animals. Histopathology revealed no olestra-related effects. Isolated incidences of soft stools, apparently resulting from the large amounts of undigested olestra, were noted in olestra-fed animals. The results of this study indicate that olestra was not toxic when fed to dogs at up to 10% of the diet for 20 months. PMID- 1894210 TI - Effects of dietary soya bean trypsin inhibitor concentrate on initiation and growth of putative preneoplastic lesions in the pancreas of the rat. AB - Two studies evaluated the effects of soya bean trypsin inhibitor concentrate (STIC) on early stages of pancreatic carcinogenesis in Wistar rats. In experiment 1, the effects of a 3-month administration of diets containing 3.7% STIC were compared with the effects of administration of diets containing 20% corn oil, in rats pretreated with a single azaserine injection sufficient to initiate putative preneoplastic atypical acinar cell foci. Experiment 2 investigated the capacity of STIC to initiate pancreatic carcinogenesis. Diets containing 3.7% STIC were fed for 4 wk, then diets containing either 5 or 20% corn oil were fed for 3 months. Pancreases were quantitatively evaluated for foci. All groups of azaserine-initiated rats had large numbers of atypical acinar cell foci per cm3 of pancreas. Of these, the group fed 3.7% STIC had pancreatic foci that occupied a significantly greater (P less than 0.01) percentage volume of pancreas than did groups fed 20% corn oil or control diets, which contained 5% corn oil and no added trypsin inhibitor. Very few or no foci were observed in all other groups of either experiment 1 or 2. STIC had a much greater effect on the growth of azaserine-induced lesions than did corn oil. STIC alone did not appear to initiate pancreatic lesions. PMID- 1894212 TI - Statistical model in tests for eye irritants. AB - A test used to classify substances for eye irritancy, as required by the Consumer Product Safety Commission, is performed on 1-3 groups of 6 albino rabbits in a sequential manner. When the statistical implications of the test are realized, it is possible for a substance to be classified as an irritant with fewer reactions than the number required for it to be classified as not an irritant. A procedure is given for correcting the inconsistency in the current test, and an alternative test, which considerably reduces the number of animals required, is proposed. Probability models and expected sample size calculations have been derived. PMID- 1894213 TI - Yields of tar and other smoke components from UK cigarettes. AB - Since 1972, regular six-monthly surveys of cigarettes on sale in the UK have determined the yields of tar, nicotine and carbon monoxide in mainstream smoke. During 1983-1990, a series of special studies investigated the yields of a range of additional analytes and their inter-relationships with the routinely monitored components. The results for total cyanide (as hydrogen cyanide), total aldehydes (including acetaldehyde), acrolein, formaldehyde and nitrogen monoxide are summarized, and the full data for six low-molecular weight phenols and three polycyclic aromatic hydrocarbons (PAHs) are reported. It is concluded that with the exception of nitrogen monoxide, which is strongly dependent upon the type of tobacco, and the delivery of some phenols and PAHs, which may be affected to a minor extent by the design of cigarette, the three routinely monitored smoke components provide an adequate guide to the yields of the other analytes examined, across the range of manufactured cigarettes available in the UK in the 1980s. PMID- 1894211 TI - Subchronic oral toxicity of cellulose acetate in rats. AB - Cellulose acetate was administered by way of a dietary admixture to Sprague Dawley rats (20/sex/group) at dose levels of 0, 500, 2500 and 5000 mg/kg body weight/day for 94-96 days. Physical observations, body weight and food consumption measurements were made before testing and throughout the study. Ophthalmoscopic examinations were conducted on all animals before testing and just prior to study termination. Haematology, clinical chemistry and urinalysis were performed at 1.5 and 3 months on 10 animals/sex/group. After 3 months of treatment the animals were killed, terminal body weights and organ weights were measured and ratios calculated. Histopathological examination of tissues from the control and high-dose groups was conducted. The evaluation of physical observations, ophthalmology, body weight, food consumption, haematology, clinical chemistry, organ-to-body-weight ratios, gross pathology and histopathology revealed no evidence of an adverse effect related to treatment with cellulose acetate. PMID- 1894214 TI - The need for animal testing--report of a case. PMID- 1894215 TI - Risk assessment of antibiotic residues of beta-lactams and macrolides in food products with regard to their immuno-allergic potential. AB - In human medicine drug allergy is a well-established side-effect of the therapeutic use of antibiotics, especially the beta-lactams. Side-effects caused by macrolides are uncommon and only a very few of these seem to be caused by allergic mechanisms. Clinically, drug allergy is characterized by a spectrum of reactions ranging from mild skin rashes to angio-oedema or life-threatening anaphylaxis. Concern has been expressed that antibiotic residues in meat and other foods might be responsible for similar hypersensitivity reactions in a small number of individuals. This review assesses the potential risk of such reactions in general, but focuses on allergy to penicillin and macrolide residues in particular. In relation to the risk of primary sensitization, it is unlikely that residues could contribute to the overall immune response in view of the very low levels that are likely to be encountered in comparison with the high levels received during therapeutic use. No evidence has been found that any individual has become sensitized by residues of either penicillins or macrolides. Furthermore, the oral route is much less sensitizing than parenteral administration and immunochemical studies with penicillin indicate that hapten protein complexes formed in vivo are unlikely to be immunogenic because of their low dose, low epitope density and binding to autologous carrier proteins. For performed allergens, the epitope density was also too low to be immunogenic. Because of the ubiquitous nature of penicillin-producing moulds in nature and the extensive use of beta-lactam antibiotics in human medicine, it is unlikely that epidemiological studies could be undertaken that could allow quantification of the minimal risk. The risk of allergic reactions in pre-sensitized individuals can be assessed similarly and again it is concluded that factors such as dose, oral administration and low epitope density make it unlikely that a significantly antigenic derivative could be formed. However, a review of the literature on penicillin hypersensitivity revealed a very small number of previously sensitized individuals from whom there is reasonable clinical and documentary evidence that penicillin residues in milk triggered an allergic reaction, usually a rash. Although these cases are very rare (less than 10 cases reported in the last 25 years), they illustrate the continuing need to control antibiotic residues vigilantly. Animal models have not proved useful for predicting the risk of hypersensitivity reactions to drugs, since allergy in man is determined by genetic and other factors and no validated methods exist to determine a no-effect level.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1894216 TI - Review of lead toxicology relevant to the safety assessment of lead acetate as a hair colouring. AB - The literature on lead toxicology has been critically reviewed to provide a safety assessment of lead acetate as a hair colouring. The main objectives were: (i) to determine the additional lead contribution from hair-colouring use to the total daily environmental lead intake; and (ii) to assess the toxicological significance of this additional contribution. The review also focuses attention on newer issues of concern over the effects of environmental lead on human health. Data available in animals and humans (including occupational exposure), mainly on lead acetate and other inorganic lead salts, have been presented and evaluated in respect of the following: absorption, distribution and excretion following ingestion; percutaneous absorption; carcinogenicity; genotoxicity; reproductive toxicity; neurological/behavioural status with particular reference to neuropsychological effects in children; and effects on other systems (e.g. cardiovascular). It is concluded that the absorption of lead from hair-colouring use represents about 0.5% of the lead absorption from the current average daily environmental lead intake. No convincing evidence could be found of any deleterious effect of current environmental lead levels on human health and thus the tiny contribution of lead acetate exposure from hair-colouring use can be regarded unequivocally as being toxicologically insignificant. PMID- 1894217 TI - Detection of IQ-type mutagens in canned roasted eel. AB - Basic extracts of canned roasted eel exhibited the highest mutagenicity among seven kinds of canned products assayed with Salmonella typhimurium TA98 in the presence of S-9 mix. The major mutagenic compounds of canned roasted eel extracts were purified and analysed by HPLC. The mutagenic fractions corresponding to the peaks of standard 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline(MeIQx) and 2 amino-3,7,8-trimethylimidazo[4,5-f]quinoxaline(7,8-DiMeIQx ) were further confirmed by the comparison of UV spectra, tester strain specificity and nitrite treatment. The estimated contents of MeIQx and 7,8-DiMeIQx were 1.1 ng and 5.3 ng per gram of canned roasted eel, respectively. Cooking temperature and time seemed to be the major factors affecting mutagen formation in fried eel. The type and amount of mutagenic compounds detected in canned roasted eel are likely to be correlated with the relative levels of specific free amino acids in raw eel. PMID- 1894218 TI - Dietary intake and risk assessment of phototoxic furocoumarins in humans. AB - The question of whether the furocoumarin content of vegetables is sufficient to induce phototoxic skin reactions after ultraviolet irradiation was examined in two experiments with four human volunteers. In a first experiment, 300 g of celery roots (total phototoxic furocoumarin content 28.2 micrograms/g) was ingested. No skin reactions were observed after UVA exposure (1.5-9 J/cm2), and the blood levels of the furocoumarins--psoralen, 8-methoxypsoralen (8-MOP) and 5 methoxypsoralen (5-MOP)--were below the analytical detection limit of 2 ng/ml. To investigate the phototoxic effects of a mixture of the two most important furocoumarins in vegetables, after gastro-intestinal uptake, 8-MOP and 5-MOP (15 mg each) were ingested separately in a 50% alcoholic solution. A strong and persistent erythema was induced in three out of the four subjects (UVA dose: 3-25 J/cm2). The blood levels immediately before UVA irradiation varied between 14 and 114 ng/ml (8-MOP), and 17 and 70 ng/ml (5-MOP). In the subject who did not show phototoxicity, the blood levels remained at trace levels (3 ng/ml). Two subjects were also tested with a mixture of 10 mg 8-MOP plus 10 mg 5-MOP; in one subject the mixture induced pigmentation only, while in the other a mild-to-medium erythema was induced. The blood levels of the furocoumarins in the two subjects were similar (12-15 ng/ml for 8-MOP and 5-MOP). It is concluded that in humans the phototoxic threshold dose of furocoumarin mixtures is of the order of 10 mg 8 MOP plus 10 mg 5-MOP, which is equivalent to about 15 mg 8-MOP per person (blood levels of 8-MOP and 5-MOP at 30 min after ingestion of about 10-15 ng/ml each). This phototoxic threshold dose was not reached by the consumption of celery roots and other conventional vegetables under normal dietary habits (experimental intake of 2-8 mg per subject of the potentially phototoxic furocoumarin mixture). However, the safety factor between the possible actual intake of furocoumarins and the phototoxic threshold dose is about 2-10, which is relatively small. PMID- 1894219 TI - Hepatic ornithine decarboxylase induction by potato glycoalkaloids in rats. AB - The induction of hepatic ornithine decarboxylase (ODC) activity in rat livers by the potato glycoalkaloids alpha-solanine, alpha-chaconine, and their aglycone solanidine, has been studied. Ip administration of alpha-solanine at 7.5, 15 and 30 mg/kg body weight produced markedly elevated enzyme activity at 4 hr after treatment, with a linear dose response. The increase was four-fold at the lowest dose administered to 12-fold at the highest. ODC activity was measured at 1, 2, 3, 4, 5, 6, 8, and 24hr after alpha-solanine was given. A statistically significant increase in enzyme activity was evident at 3 hr after treatment; maximal activity occurred at 5 hr and was approximately 12 times greater than the dimethylsulphoxide (DMSO) control level. Elevated activities persisted for several hours, decreasing to about one-third of the maximal level at 8 hr. The relative effects of alpha-solanine, alpha-chaconine and solanidine on ODC activities were studied at 4 hr using an equimolar dose of 17 mM/kg body weight. ODC activity induced by alpha-chaconine was higher than that induced by alpha solanine; the latter activity was two-thirds that of the former. The aglycone solanidine did not induce any increase in activity compared with the DMSO control. ODC activity with dexamethasone, a glucocorticoid, at 4 mg/kg body weight, followed a pattern similar to that of alpha-solanine. However, maximal activity occurred slightly earlier at 4 hr after treatment. The results show that the extent of induced ODC activity depends on the structure of the potato alkaloid. PMID- 1894220 TI - Developmental toxicology of potato alkaloids in the frog embryo teratogenesis assay--Xenopus (FETAX). AB - Potatoes frequently contain growth inhibitors and toxic compounds including digestive enzyme inhibitors, lectins and glycoalkaloids. The literature suggests that Solanum alkaloids have the ability to induce neurological damage such as spina bifida and other malformations. As part of a programme of improvement in the safety of potatoes using molecular plant genetics and parallel food safety evaluation, we evaluated the effect of several potato glycoalkaloids and aglycones in the frog embryo teratogenesis assay--Xenopus (FETAX) with and without metabolic activation by Aroclor 1254-induced rat liver microsomes. The data suggest that the glycoalkaloid alpha-chaconine is teratogenic and more embryotoxic than alpha-solanine, in terms of the median lethal concentration (LC50) after 96 hr of exposure, the concentration inducing gross terata in 50% of the surviving frog embryos (96-hr EC50, malformation), and the minimum concentration needed to inhibit the growth of the embryos. Since these two compounds differ only in the nature of the carbohydrate side chain attached to the 3-OH group of solanidine, the side chain appears to be an important factor in governing teratogenicity. The aglycones demissidine, solanidine and solasodine were less toxic than the glycosides alpha-chaconine and alpha-solanine. The in vitro teratogenesis assay should be useful for: (a) predicting the teratogenic potential of solanaceae alkaloids, glycoalkaloids and related natural products; and (b) facilitating experimental approaches to suppress plant genes and enzymes that control the biosynthesis of the most toxic compounds. PMID- 1894221 TI - Oncogenicity study of trifluralin in B6C3F1 mice. AB - B6C3F1 mice were maintained for 24 months on diets containing 0, 563, 2250 or 4500 ppm trifluralin. These dietary concentrations corresponded to daily doses of approximately 70, 285 or 570 mg/kg body weight, respectively. The control group contained 120 mice/sex and treated groups consisted of 80 mice/sex. There were no treatment-related effects on the survival, appearance or behaviour of the mice. Survival at test termination was at least 67% in each group. Compared with controls, mean body weight was significantly reduced in a dose-related manner in mice of both sexes given the 2250 and 4500 ppm diets. At 21 months, the reduction in body weight was greater than or equal to 15 and greater than or equal to 30%, respectively. At study termination, dose-related decreases in erythrocytic and leucocytic values were also observed at dietary levels of 2250 and 4500 ppm. In clinical chemistry evaluations, blood urea nitrogen levels and alkaline phosphatase activity in mice of both sexes were significantly increased at trifluralin levels of 2250 and 4500 ppm. Blood urea nitrogen also showed a marginal increase in females given the low dose of trifluralin. Alanine aminotransferase activity was significantly increased in males at all treatment levels. Although there were a number of absolute and relative organ weight changes in all three treatment groups that were significantly different from the control values, the reduced relative kidney weights in males and the increased relative liver weights in both sexes at dietary levels of 2250 and 4500 ppm were the only changes that could be correlated with altered clinical chemistry values.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1894222 TI - Formation of DNA adducts in F-344 rats after oral administration or inhalation of [14C]methyl bromide. AB - The genotoxic effects of methyl bromide were investigated in a DNA-binding study. [14C]Methyl bromide was administered to male and female F-344 rats orally, or by inhalation from a closed exposure system. DNA adducts were detected in the liver, lung, stomach and forestomach. [14C]3-Methyladenine, [14C]7-methylguanine and [14C]O6-methylguanine were identified using a combination of three different methods of hydrolysing DNA, followed by HPLC or gas chromatography-mass spectrometry. After both oral and inhalation exposure, the highest levels of methylated guanines, especially those of [14C]O6-methylguanine, were found in the stomach and forestomach of the rats. These results clearly demonstrate a systemic DNA-alkylating potential of methyl bromide. PMID- 1894223 TI - Effects of reserpine and L-cysteine and glutathione depletion on 2 bromoethylamine hydrobromide-induced tubular necrosis in Swiss ICR mice. AB - Female Swiss ICR mice were injected ip with 100 or 300 mg 2-bromoethylamine hydrobromide (BEA)/kg body weight. Male Swiss ICR mice were subjected to water deprivation, or treated with 5% dextrose in water, dimethylsulphoxide, piperonyl butoxide, SKF-525A, sodium phenobarbital, beta-naphthoflavone, probenecid, reserpine, diethyl maleate, buthionine sulphoximine or L-cysteine. Urine collected sequentially from male Swiss ICR mice given 300 mg BEA/kg body weight was analysed for glucose, protein, pH and specific gravity. Female mice were less sensitive to BEA than were male mice. Diuresis, antidiuresis, treatment with cytochrome P-450 inducers and inhibitors, and the antioxidant dimethyl-sulphoxide had no effect on the incidence or severity of tubular necrosis (TN) induced by BEA. Probenecid and L-cysteine decreased the severity, but they had no effect on the incidence of TN. Glutathione depletion by diethyl maleate and inhibition of glutathione synthesis by buthionine sulphoximine decreased the dose of BEA necessary to cause TN; buthionine sulphoximine was more effective than diethyl maleate. Reserpine decreased both the incidence and severity of TN. Glycosuria, aciduria and decreased urinary specific gravity occurred before morphological changes were seen under the microscope, indicating that the functional changes precede the morphological changes. These data indicate that glutathione is important in protecting against BEA-induced TN, that BEA or a metabolite is concentrated in the tubule epithelium by way of anion transport, and that vasoconstriction contributes to the development of BEA-induced TN. PMID- 1894224 TI - Maleic acid dimethylester: evaluation of dermal toxicity and genotoxicity. AB - Maleic acid dimethylester (MAD) was investigated in acute and subacute dermal toxicity studies, for sensitization potential, and for in vivo and in vitro genotoxicity. The acute dermal toxicity in rats was low (LD50 greater than 2000 mg/kg body weight). Only local effects, erythema and necrosis, occurred at the site of application. Corresponding dose-related effects were observed in a 28-day repeated dermal toxicity study in rats. Treatment-related systemic alterations were observed in feed consumption, body weights, haematology and clinical chemistry at 170 and 500 mg MAD/kg body weight. Based on the results of this study, the no-toxic-effect level of MAD was considered to be 60 mg/kg body weight/day. However, slight dermal irritative effects were also present at the lowest dose level (60 mg/kg body weight). The primary skin irritation test in rabbits showed only slight erythema and oedema. The results of the maximization test in guinea-pigs indicated a clear sensitizing potential of MAD. In the Ames test, with five strains of Salmonella typhimurium, MAD was not mutagenic up to the highest dose level of 5000 micrograms/plate. In the micronucleus test, in which mice were given 1000 mg MAD/kg body weight by gavage the compound revealed no clastogenic effects. PMID- 1894226 TI - Metatarsal head resection for bunionette: long-term follow-up. AB - We studied 11 feet of seven patients who underwent resection of the distal fifth metatarsal for bunionette at our institution, with an average follow-up of 9.1 years and a minimum follow-up of 8.0 years. Results from 11 feet were good in two, fair in two, and poor in seven. Causes of failure were transfer metatarsalgia, persistent lateral forefoot prominence, and painful fifth toe deformity. Complications occurred in 64% and included transfer metatarsalgia and painful fifth toe deformity. Two patients underwent revision operation and in two instances additional operation was requested. Resection of the distal fifth metatarsal is not recommended for initial operative treatment of the bunionette. PMID- 1894225 TI - Effect of manganese on biogenic amine metabolism in regions of the rat brain. AB - The effect of prolonged exposure to low-level manganese (Mn) on regional levels of biogenic amines in the rat brain was studied. Rats were given Mn in drinking water for 90 days, which resulted in a two- to three-fold accumulation of Mn in all regions of the brain. After exposure, dopamine beta-hydroxylase (DBH), monoamine oxidase (MAO), dopamine (DA) and serotonin (5-HT) were measured in regions of the brain. There was a significant inhibition of DBH in the striatum (P less than 0.01), hypothalamus (P less than 0.01), mid-brain (P less than 0.001) and cortex (P less than 0.01). MAO was also decreased significantly in the cerebellum and cortex (both P less than 0.01). The striatum showed a decrease in DA content, but this was not significant. However, the hippocampus showed a significant decrease (P less than 0.01) and the mid-brain showed a significant increase (P less than 0.01) in DA levels. No significant changes were observed in 5-HT levels in any region, except for an increase in the cortex (P less than 0.01). It was observed that prolonged exposure of rats to low-level Mn affects both DBH and MAO, and that this effect is region-specific. However, the effect of Mn on biogenic amines seems to be variable, and this might explain the variable signs and symptoms observed in the various phases of Mn toxicity in humans. PMID- 1894227 TI - Vascular anatomy of the fifth metatarsal. AB - The extraosseous and intraosseous vascular anatomy to the fifth metatarsal as visualized in a group of below-the-knee amputation specimens has been described. The extrinsic circulation to the area is provided by the dorsal metatarsal artery, the plantar metatarsal arteries, and the fibular plantar marginal artery. These three source arteries supply branches to the metatarsal and adjacent joints. The intraosseous vascularity consists of a periosteal plexus, a nutrient artery, and a system of metaphyseal and capital vessels. PMID- 1894228 TI - The lateral ligamentous support of the subtalar joint. AB - A review of the ligamentous structures spanning the subtalar joint laterally, as well as within the sinus and canalis tarsi, is presented based on previous descriptions and a series of anatomic dissections. Defined supporting structures are categorized into superficial, intermediate, and deep layers. Of these, the inferior extensor retinaculum is seen to be a discrete, substantial structure readily accessible for ligament reconstructions involving both the ankle and subtalar joints. PMID- 1894229 TI - Repair of fibular ligaments: comparison of reconstructive techniques using plantaris and peroneal tendons. AB - The results of treatment of chronic ligamentous insufficiency of the lateral hindfoot using plantaris tendon grafting (52 ankles) or peroneal tenodesis (128 ankles) were compared with an average followup of 66 months. In two-thirds of all cases an instability of the subtalar joint was present, isolated or combined with an instability of the talocrural joint. The overall outcome with both methods was good, but the results after plantaris repair were slightly more favorable. This fact is underlined by the frequency of reoperations: 1.9% after plantaris repair compared with 9.4% after peroneal tenodesis. We conclude that plantaris repair is the method of choice. PMID- 1894230 TI - Loading of the contralateral foot in peripheral vascular insufficiency below-knee amputees. AB - Seven ambulatory peripheral vascular insufficiency below-the-knee amputees underwent gait analysis to determine the local pressures on seven prominent plantar regions in their remaining limb. Patients occupied significantly less stance phase time on their remaining limbs. Peak, mean, and total pressures measured at each of the seven prominent areas was decreased as compared with laboratory age and sex matched controls. The results of this study suggest that the risk of contralateral limb amputation surgery is related to systemic peripheral vascular insufficiency or local factors, and not increased loading of the remaining contralateral "limb-at-risk." PMID- 1894231 TI - Long-term followup of physeal injury to the ankle. AB - Sixty-eight patients with a distal physeal injury to the tibia and/or the fibula were reviewed, with an average followup of 27 years and 4 months from the initial lesion. The average age at injury was 12 years and 6 months, whereas the average age at follow-up was 40 years. Seventeen patients had a type I Salter-Harris injury, 27 type II, 10 type III, and 14 type IV. All the patients but six were treated conservatively. According to our criteria of evaluation, 47 patients had a good result, 13 fair and eight poor. The type of Salter-Harris lesion, the amount of the initial displacement and the quality of reduction were the three main parameters which determined the end-result. Radiographic signs of osteoarthritis were present in 11.8% of our patients and all of them had presented type III or IV lesions, except for one who had a type II lesion. PMID- 1894232 TI - Cadaver correlation of peroneal tendon changes with magnetic resonance imaging. AB - Magnetic resonance imaging (MRI) is used to show the soft tissues of the body. The presence of anomalous tendons and muscles can be detected. Chronic lateral ankle pain and instability can be associated with peroneal tendon pathology and MRI may be used to assess both longitudinal attrition of the peroneus brevis tendon, as well as the presence of the peroneus quartus which may be useful in lateral ankle reconstruction. Tenography can occasionally present technical difficulties and can lead to patient dissatisfaction. PMID- 1894233 TI - Biomechanical evaluation of the anterior drawer test: the contribution of the lateral ankle ligaments. AB - The contributions of the lateral ankle ligaments to resisting anterior-posterior displacement of the talus were evaluated in eight unembalmed cadaveric ankles. While holding the distal tibia fixed, loads of 150 N were applied to the talus in the anterior and posterior directions in the neutral, dorsiflexed, and plantarflexed positions using an hydraulic test system. Tests were performed on the intact specimens then after sequential sectioning of the lateral ligaments of the ankle. Under strictly anteroposterior loading and without an axial (weight bearing) load applied, no single ligament could be isolated as having a dominant stabilizing function. PMID- 1894235 TI - Fixation of the proximal first metatarsal crescentic osteotomy with the small cannulated screw system. PMID- 1894234 TI - Syme's two-stage amputation in insulin-requiring diabetics with gangrene of the forefoot. AB - Thirty-five insulin-requiring adult diabetic patients underwent 38 Syme's Two Stage amputations for gangrene of the forefoot with nonreconstructible peripheral vascular insufficiency. All had a minimum Doppler ischemic index of 0.5, serum albumin of 3.0 gm/dl, and total lymphocyte count of 1500. Thirty-one (81.6%) eventually healed and were uneventfully fit with a prosthesis. Regional anesthesia was used in all of the patients, with 22 spinal and 16 ankle block anesthetics. Twenty-seven (71%) returned to their preamputation level of ambulatory function. Six (16%) had major, and fifteen (39%) minor complications following the first stage surgery. The results of this study support the use of the Syme's Two-Stage amputation in adult diabetic patients with gangrene of the forefoot requiring amputation. PMID- 1894236 TI - Rupture of the posterior tibial tendon associated with closed ankle fracture. AB - Rupture of the posterior tibial tendon has rarely been associated with closed ankle fractures. All previous cases have been in association with pronation external rotation type fractures in which the medial malleolus has been fractured. This case represents the first such report of a severed posterior tibial tendon in the absence of a medial malleolar fracture and reemphasizes the importance of critically evaluating intraoperative radiographs following the open reduction and internal fixation of closed ankle fractures to assess the possibility of soft tissue interposition. In the event of an acute rupture of the posterior tibial tendon, the authors recommend primary tendon repair. PMID- 1894237 TI - Os trigonum syndrome: a clinical entity in ballet dancers. AB - Thirteen Swedish National classic ballet dancers were surgically treated for an "os trigonum syndrome."Their main symptom was an impingement pain in the hind foot while actively plantarflexing the ankle during ballet dancing. The surgical procedure included excision of an os trigonum or a prominent lateral posterior process of the talus, together with division of the flexor hallucis tendon sheath if it was thickened. This procedure was safe and resulted in return of the dancers to the same level of ballet dancing within 5 to 10 weeks. PMID- 1894238 TI - Rupture of the flexor hallucis longus after hallux valgus surgery: case report and comments on technique for adductor release. AB - A case of flexor hallucis longus (FHL) rupture following hallux valgus surgery is reported here. The authors conjecture that the FHL rupture was caused by a partial laceration of the FHL at the time of the surgical hallux valgus correction. The authors treated the painful problem by surgically debriding the distal stump of the FHL from under the first metatarsophalangeal joint (MP) and tenodesing that the proximal stump to the flexor digitorum longus (FDL). The authors describe a technique that minimizes the complications of an adductor tenotomy associated with a distal chevron type of hallux valgus correction. PMID- 1894239 TI - Perineural fibrosis of the superficial peroneal nerve complicating ankle sprain: a case report. PMID- 1894240 TI - [The wear-timing measuring device in orthodontics--cui bono? Reflections on the state-of-the-art in wear-timing measurement and compliance research in orthodontics]. AB - The recent development of fully functioning timing devices has yielded a new impulse to scientific research on orthodontic compliance. In contrast, promises and risks of the practical application of timing devices have thus far largely gone unheeded. In this survey, possible benefits of this new device are considered along with a critical discussion of technical and sociopsychological issues of its practical application. Following a review of the current state of orthodontic timing technology, basic implications of the collection and utilization of this new type of data are outlined. Short- and long-term perspectives of objective measurement of compliance are presented in terms of optimized treatment devices, enhanced patient compliance and improved orthodontist-patient relations. An evaluation project on benefits and risks of orthodontic timing devices is being called for. PMID- 1894241 TI - [The anatomical and physiological aspects in the treatment of temporomandibular joint disorders]. AB - The specialty of orthodontics and its relationship to TMJ problems is in the thick of controversy. Several anatomic and physiologic aspects are discussed so as to improve the understanding of the multi-faceted problems. The use of this biologically-based information is likely to make therapy more successful. From a therapeutic point of view, it is incumbent on the dentist to institute early preventive or interceptive procedures. PMID- 1894242 TI - [Orthodontic measuring and simulating systems (OMSS) for the static and dynamic analysis of tooth movement]. AB - An orthodontic measurement and simulation system (OMSS) is presented. The major components of this system are two measuring tables each comprising a force/torque sensor and a motor driven, fully three-dimensionally adjustable positioning stage. The force/torque sensors are capable of measuring simultaneously all forces and torques acting on a tooth. Using the computer program "OMSS" which runs on a personal computer, several different measurements can be conducted. On the one hand, the system supports absolute measurements such as the registration of a force/deflection diagram. Furthermore, even multidimensional force/deflection- or torque/distance curves can be measured. On the other hand, simulations of orthodontic tooth movement can be conducted. In such simulations, the force system acting on a tooth is measured and the resulting tooth movements are calculated. By using this "computer typodont", not only the static but the dynamic behaviour of orthodontic appliances can be studied. The application of this system is demonstrated by the analysis of several orthodontic problems. PMID- 1894244 TI - [Anterior tooth intrusion with the base arch: preactivation by tip-back bending or curvature?]. AB - Burstone's intrusion mechanics has been found to be effective in the treatment of a deep bite due to intrusion of the anterior teeth. The pre-activation of the intrusion arch by a tip-back bending shows a shortening in the activation. Measurements objectified the extent of the shortening and the resulting horizontal forces for TMA arches of a dimension of 0.017 x 0.025 inch relating to different distances between molars and anterior teeth and pre-activation by means of tip-back bending or curvature. The change of the vertical force in connection with a simulated intrusion of 5 mm was also registered. Clinical consequences of the therapy are discussed. PMID- 1894243 TI - [Arch-guided tooth movement--its dynamics, efficacy and side effects]. AB - Canine retraction on a continuous arch wire was simulated using the OMSS. The influence of wire dimension, force generating element (power chain, coil spring, powerhook, uprighting spring), bracket width and the position of the center of resistance on the effectiveness of the distalization of the canine and its side effects such as extrusion, rotation and tipping were examined. Stainless steel, nickel titanium and multi-stranded wires were tested. Employing the 0.018"-slot system, the use of an 0.016" X 0.022"-arch wire gave the best results. Comparing the NiTi coil spring with the elastic chain, the former should be preferred, because, due to its low load deflection it generates a nearly constant force over a wide range of activation. Using powerhooks or uprighting springs, a nearly bodily movement could be achieved. On the other hand, friction may increase if the uprighting is too strong. The rate of tooth movement decreases by increasing length of tooth root represented by the position of the center of resistance. Arch guided tooth movement along multi-stranded wires shows a high effectiveness, nevertheless, these wires should not be used for canine retraction because of the above mentioned side effects. PMID- 1894245 TI - [Space closure after anterior tooth loss due to trauma]. AB - The orthodontic treatment of space closure after loss of anterior teeth due to trauma asks not only for a dental movement but for careful consideration. These depend on various factors such as age, tooth shape, tooth size, extent of the traumatic damage and the present malocclusion. The possibilities and limits of an orthodontic treatment have to be estimated to allow a correct decision for each patient, whereby some compromise has to be accepted. This is demonstrated with two examples. PMID- 1894246 TI - [The tooth transplant in orthodontic treatment planning]. AB - The analysis of all examined transplant cases combined treated with orthodontics shows a success rate of 76%. It must be underlined that the germ development at the time of the transplantation is of utmost importance. The best possible time proved to be at a root development of 2/3 to 3/4. Exact indication position, a careful atraumatic operation method and a short time of operation are also important factors of a successful transplantation. If all these preconditions are met, this method can be recommended. PMID- 1894247 TI - [The stability of orthodontic treatment results]. AB - A posttreatment evaluation of 72 patients, who are approximately 5.8 years out of retention, showed only little changes between the last appointment and the follow up examination. The results can be considered stable. The statistic analysis indicated a correlation among some changes, which are important for treatment and therapy planning. For the stability in transversal and sagittal direction a maximal intercuspidation of the premolars and molars is as important as the exact positioning of the canines with lateral contacts in the dental arch. Transversal over-expansion should be avoided, because those results cannot be stabilized in the postretention period. The functional adaptation of muscles, the abolishment of habits and the duration of retention are essential preconditions for a stable treatment result. PMID- 1894249 TI - [Orthodontic surgical treatment of class III--the electromyographic effects on the masticatory and facial musculatures]. AB - 22 adult class-III patients, partly with considerable vertical excess, who required combined orthodontic-surgical treatment were investigated at the end of preoperative orthodontic treatment and six months postoperative. EMG activity was recorded for the m. temporalis, m. masseter, perioral and the floor of the mouth muscles during rest position and in six different active functions. Postoperative activities revealed a significant reduction for most muscles in almost all functions. Additionally right-left differences were reduced. This effect is regarded to be a sign of more efficient muscular action due to improved biomechanical and occlusal conditions so that defined functions can be exerted by less muscular activation. PMID- 1894248 TI - [Data analysis in long-term follow-ups of previously treated orthodontic patients]. AB - The structure of former orthodontically treated patients, who underwent a long term follow-up study in October 1989, was evaluated. An attempt was made to contact 1429 former patients, whereby 28.8% did not get the invitations because they had changed their address. As the compliance of approximately 17 years postretention of the 1,018 patients depends on change of address, job, interest and death, 20% of these were willing to participate and get examined. A structural conformity of the controlled group and the patient total cannot be presumed due to the patients' answers in the follow-up study. Questionnaires will be sent to patients, who did not participate in the analysis, in order to avoid unilateral results. PMID- 1894250 TI - The moral of clozapine. PMID- 1894251 TI - Ensuring highest-quality care for the cost: coping strategies for mental health providers. PMID- 1894252 TI - Taste, food exposure, and eating behavior. PMID- 1894253 TI - Strategies for integrating public mental health services. AB - Practical solutions to the issues troubling public mental health systems must be developed within the constraints of existing political structures. A key enabling factor is the inclusion of a broad range of reimbursable mental health benefits within health insurance. However, services cannot be improved without the development of viable frameworks for organizing effective service delivery; such strategies include assertive community treatment, capitation approaches, strong local mental health authorities, and reimbursement structures that achieve key objectives. The author discusses examples of the four strategies and argues for their better integration. PMID- 1894254 TI - Prevalence of somatic and psychiatric disorders among former prisoners of war. AB - American former prisoners of war (POWs) are an aging group who seek health care with increasing frequency. To examine the prevalence of long-term physical and emotional consequences of captivity in this population, the authors analyzed medical and psychiatric examination data for 426 former POWs. Detailed psychiatric diagnostic criteria were used to assess the POWs' mental health. Compared with general population groups, POWs had moderately elevated lifetime prevalence rates of depressive disorders and greatly elevated rates of posttraumatic stress disorder (PTSD), although their rates of hypertension, diabetes, myocardial infarction, bipolar disorder, schizophrenia, and alcoholism were not elevated. POWs who lost more than 35 percent of their body weight during captivity had higher rates of anxiety disorder, depressive disorders, PTSD, and schizophrenia, compared with other POWs. PMID- 1894255 TI - A problem-solving approach to group psychotherapy in the inpatient milieu. AB - Because of the trend toward a marked decrease in length of psychiatric hospitalization, clinicians need to improve the organization of the therapeutic milieu so that behavioral changes can be effected more rapidly. A university general psychiatric unit has adapted a problem-solving model that integrates groups and activities so that each one focuses on complementary behavioral objectives for each patient with the aim of effecting more rapid behavior change. The stages of the model are incorporated in a weekly sequence that begins with a goal-setting group. In a series of subsequent groups, each patient tries to develop and implement a solution to the problem identified that week. At the end of each week, patients participate in a goal review group, with feedback from staff and peers and self-reinforcement. The model can be used with a diverse patient population without interfering with each patient's individual psychotherapy or pharmacotherapy. PMID- 1894256 TI - Effect of evaluations of competency to stand trial on the state hospital in an era of increased community services. AB - The authors studied court-ordered inpatient evaluations of competency to stand trial at two Massachusetts state hospitals for the period from 1972 to 1987, with particular attention to the effects of a 1978 federal court consent decree that created an extensive system of community-based services in the catchment area of one of the hospitals. The authors found that the broad array of community services developed under the consent decree did not reduce commitments to the state hospital for evaluation of competency to stand trial at the same rate as it reduced civil commitments, with the result that the composition of the patient population changed to include a significantly larger proportion of patients referred by the criminal justice system. This proportion was as high as 17.8 percent in 1985. These patients used a disproportionate share of the hospital's resources, staying in the hospital for a median of 28 days, compared with 12 days for all other patients. PMID- 1894257 TI - A checklist of hospitalization criteria for use with children. AB - Each year in the U.S. more than 130,000 children are hospitalized for psychiatric reasons. The decision to hospitalize a child is based on a complex set of factors. In this study, a 12-item checklist of criteria for hospitalization adapted by the authors was tested for its ability to predict hospitalization in a cohort of 389 children between the ages of two and 12 who were evaluated for either inpatient or outpatient treatment. Eighty-seven (22 percent) of the children were subsequently hospitalized. In 95 percent of the cases, the checklist was able to correctly predict whether the patient was hospitalized. A shorter checklist of six items was also able to predict the subsequent form of treatment in 95 percent of the cases. Although such checklists cannot take the place of informed clinical decisions, they can serve as a guide to decision making, especially for inexperienced mental health workers, and as a tool for utilization review when treatment decisions are questioned. PMID- 1894258 TI - Developing new certificate-of-need regulations for inpatient care of children in New York State. AB - In 1988 New York State imposed a moratorium on the development of new psychiatric beds for children because the state's certificate-of-need law lacked objective criteria for evaluating applications. The following year the department introduced revised certificate-of-need regulations that incorporated more specific program criteria, based on the department's policies, as well as a quantitative methodology for estimating the number of children's beds needed in general hospitals and private specialty hospitals. The methodology led to a planning figure of 10,000 admissions of children to acute care for 1995. It disaggregated the expected admissions to each of the state's 15 children's service areas and also established expected average lengths of stay for each service area. The authors outline the program criteria, the bed-need methodology, and results of the calculations. PMID- 1894259 TI - Influence of substance abuse and mental disorders on emergency room use by homeless adults. AB - Substance abuse and mental disorders increase the health care needs of homeless persons, whose primary source of care is often the emergency room. In this study, associations between substance abuse and mental health problems and use of emergency rooms were examined using data from a 1987 survey of 1,152 homeless adults in New York City shelters. Two-thirds (N = 767) of the sample reported using an emergency room at least once in their lives, and 27.2 percent (N = 313) reported use within the previous six months. Traumatic injury was the most frequently cited reason for the last emergency room visit. Respondents who reported psychotic ideation during the previous year or severe depressive symptoms during the previous week were much more likely to have used an emergency room within the previous six months. The preliminary findings suggest that substance abuse and mental disorders play a significant role in emergency room use by homeless adults. PMID- 1894260 TI - A supported education program for young adults with long-term mental illness. AB - Fifty-two young adults with severe psychiatric disabilities were selected to participate in a university-based supported education program aimed at helping them develop the skills to choose and implement a career plan. Thirty-five of the subjects completed the four-semester program. After the intervention, 42 percent of the students were competitively employed or enrolled in an educational program, compared with 19 percent before the intervention. The number of hospitalizations experienced by the subjects in the first year of the program decreased significantly, and the subjects' self-esteem increased significantly. The results indicate that rehabilitation services on a university campus may be a viable adjunct to more traditional rehabilitation services for persons with psychiatric disabilities. PMID- 1894261 TI - Group activity and cognitive improvement among patients with Alzheimer's disease. PMID- 1894262 TI - Comorbidity and treatment outcome of inpatients with chronic combat-related PTSD. PMID- 1894263 TI - Validity of psychiatric patients' self-reports of rehospitalization. PMID- 1894264 TI - Mass phenomena at a black South African primary school. PMID- 1894265 TI - Factors predicting inpatient length of stay in a CMHC. PMID- 1894266 TI - Sexual behavior of hospitalized chronic psychiatric patients. PMID- 1894267 TI - Unrecognized physical illness. PMID- 1894268 TI - Problems with interpreters. PMID- 1894269 TI - Data watch. Second-quarter HAS/Monitrend II data from AHA. PMID- 1894270 TI - Key players must help shatter the glass ceiling, say experts. AB - Women are continuing to move up through the management pipeline in hospitals across the country; but is top management prepared? Although many women are aiming for the highest levels in management, a recent survey of female and male health care executives indicates that critical changes must be made by top management and boards of hospitals before those women can continue to advance accordingly. Meanwhile, women's experience as senior executives has been quite different from men's, the survey also shows. PMID- 1894271 TI - Developing a winning strategy for managed care contracting. AB - Hospitals are learning some important lessons these days about managed care contracting. Many are moving away from automatically signing every managed care contract that comes their way. Instead, they are planning carefully for the future by developing an overall contracting strategy and by using a variety of techniques to save money. PMID- 1894272 TI - Narrow 'safe harbors' may create tough choices for hospitals. AB - The release of the "safe harbors" regulations by the Department of Health and Human Services has left a variety of important issues unresolved. Health care attorneys and their clients are now poring over the new regulations, trying to determine, among other things, how much risk tolerance to accept in relation to the new restrictions, and what level and types of monitoring the federal government will apply. Ultimately, say many experts, the regulations could result in a strong trailoff in joint venture volume. PMID- 1894273 TI - Will Amex pull out of the hospital market? AB - Most of the time, the information system vendors who abandon hospital clients are small and relatively unknown companies. Now, however, it appears that a major play in the hospital information systems market may pull out; rumors of its problems are making its clients nervous. PMID- 1894274 TI - New rules of success for outpatient facilities. AB - The recent revolution in outpatient care has rearranged the rules of thumb for hospital construction. While the vast majority of hospital facilities were designed for inpatient care, the biggest growth area is now outpatient, resulting in a need to rethink outpatient care site planning. PMID- 1894275 TI - Six associations draft guidelines for billing audits. PMID- 1894276 TI - New study: more MDs will seek management jobs. PMID- 1894277 TI - CEO firings: warning signs of unhappy boards. AB - There are a number of classic warning signs that a CEO's firing is imminent, experts say. Chief among these: when the board or a board component begins meeting without the CEO; or when unhappy trustees redirect the administrator to change policy or reconsider decisions. PMID- 1894278 TI - Why nurses become entrepreneurs. PMID- 1894280 TI - Ten strategies for increasing your self-confidence. PMID- 1894279 TI - Who, me? Write? PMID- 1894282 TI - Everything is relative. PMID- 1894281 TI - Streamlining the paper writing process. PMID- 1894283 TI - Imprint 1991 publishers directory. Resource books for nursing students. PMID- 1894284 TI - The interview. PMID- 1894286 TI - Living wills. PMID- 1894287 TI - Nursing's agenda for health care reform. PMID- 1894285 TI - Nursing informatics offers interesting career path. PMID- 1894288 TI - Nursing in a migrant setting. PMID- 1894290 TI - Florence Nightingale, RN, MBA, Inc. PMID- 1894289 TI - "Why I chose nursing as a career". PMID- 1894291 TI - Being a nurse attorney. PMID- 1894292 TI - Being a nurse politician. PMID- 1894293 TI - Antitachycardia pacing: electrophysiologic concepts and clinical experience. PMID- 1894295 TI - Significance of myocardial ischaemia before cardiac catheterisation in patients with ischemic heart disease. AB - Eighty one patients with ischemic heart disease divided in four groups (group 1, n = 24, without ischemia; group II, n = 20, myocardial ischemia before invasive procedure; group III, n = 18, myocardial ischemia during invasive procedure, group IV, n = 19, myocardial ischemia before and during the invasive procedure) were studied at rest, by bicycle ergometric exercise test and cardiac catheterisation (including selective coronary angiography) to assess the response of autonomic nervous system as judged by the non-invasive parameters of myocardial oxygen demand. Patients in group II and IV had increased double product before the invasive procedure, diminished coronary reserve and left ventricular ejection performance although the vessel involvement in these groups was similar to that of other two groups. Patients with ischemic heart disease manifest different degree of myocardial ischemia before and during cardiac catheterisation depending upon the activity of autonomic nervous system. PMID- 1894294 TI - Restenosis after successful coronary angioplasty in single vessel disease. AB - One hundred and ninety five patients who underwent successful percutaneous transluminal coronary angioplasty (PTCA) for single vessel disease and have been followed up for more than 6 months are being reported. Angiography was done routinely in first 20 patients (Group 1) 8 to 15 weeks (mean 9.6 weeks) after PTCA. Restenosis (loss of 50% of the initial improvement in luminal diameter) was seen in 4 patients (20%). The remaining 175 patients (Group II) have been followed up clinically and subjected to serial exercise testing. Coronary angiography was performed only if symptoms and/or objective evidence of ischemia recurred. In this group, restenosis suspected clinically and confirmed by angiography occurred in 37 patients (21%), 2 to 23 weeks (mean 12.5 weeks) after PTCA. The restenosis rate for the entire patient population was 21%. In general the restenosed lesions were longer and tighter than the lesions before PTCA. A comparison of 41 patients with restenosis with those who did not have clinical restenosis revealed a proximal left anterior descending artery (LAD) involvement (66% vs 31%, p = 0.01), crescendo unstable angina (37% vs 16% p = 0.05), length of pre PTCA stenotic lesion greater than or equal to 1 cm (41% vs 27.5%, p less than 0.05), absence of intimal haziness in immediate post PTCA angiogram (27% vs 16%, p less than 0.05) and residual stenosis greater than or equal to 25%, (34% vs 14% p less than 0.05) in the restenosis group. Repeat PTCA was done in 30 patients with a 96% success rate; 4 patients required coronary artery bypass grafting (CABG). Restenosis after PTCA is a significant problem in our experience.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1894296 TI - Effect of intravenous oxyfedrine on exercise in patients with ischaemic heart disease. AB - In a double blind crossover trial, acute effects of 8 mg intravenous oxyfedrine were compared with those of placebo in 18 patients with stable effort angina assessed by treadmill exercise testing. In the resting state, oxyfedrine caused an increase in heart rate (84 +/- 23 to 103 +/- 19 bpm, p less than 0.01), systolic blood pressure (123 +/- 16 to 133 +/- 20 mmHg, p less than 0.01) and double product (11 x 10(3) +/- 2 x 10(3) to 13.7 x 10(3) +/- 3.1 x 10(3), p less than 0.01) as compared to placebo. However, these parameters were not significantly different at the end of first or second stage of the treadmill test (p = NS). Time to one mm ST segment depression was increased with oxyfedrine as compared to placebo (1.5 +/- 1.5 to 1.9 +/- 1.5 minutes, p less than 0.05). Oxyfedrine did not increase the total duration of exercise (4.1 +/- 1.0 to 4.7 +/ 2.2 minutes, p = NS) or time to ischaemic symptoms (2.7 +/- 1.3 to 2.9 +/- 1.9 minutes, p = NS). The total work done was significantly more on oxyfedrine 312 +/ 189 joules/kg to 370 +/- 209 joules/kg, p less than 0.01) as also the double product achieved (20.6 x 10(3) +/- 6.1 x 10(3) to 22.5 x 10(3) +/- 6.4 x 10(3), p less than 0.01). It is concluded that intravenous oxyfedrine improves exercise capacity in patients with stable effort angina presumably by reducing myocardial ischaemia. PMID- 1894297 TI - Profile of coronary artery disease in Indian women: correlation of clinical, non invasive and coronary angiographic findings. AB - Clinical and risk factor profile of 101 consecutive female patients subjected to coronary angiography was analysed. Coronary angiography showed single vessel disease (SVD) in 15.8 per cent, double vessel disease (DVD) in 12.9 per cent, triple vessel disease (TVD) in 39.6 per cent and normal coronary arteries (NC) in 30.7 per cent. Risk factor profile in patients with angiographic coronary artery disease (group II) included hypertension (HT) in 52.9 per cent, diabetes mellitus (DM) in 44.3 per cent, post menopausal state in 84.3 per cent, positive family history in 51.4 per cent, obesity in 58.3 per cent, low density and high density lipoprotein ratio (LDL/HDL) more than 3.0 in 58 per cent and smoking in 4.3 per cent. Risk factors in 31 patients with NC (group I) included HT in 29 per cent, DM in 6.5 per cent, positive family history in 45.2 per cent, obesity in 45.2 per cent, post menopausal state in 48.4 per cent, LDL/HDL ratio more than 3.0 in 30 per cent and smoking in none. The clinical presentation in group II was unstable angina in 64.3 per cent, stable angina pectoris in 24.3 per cent, myocardial infarction in 4.3 per cent and atypical chest pain in 2.8 per cent. In group I half the patients presented with atypical chest pain. The other modes of presentation included unstable angina 25.8 per cent, stable angina pectoris in 16.2 per cent and myocardial infarction in 6.5 per cent. Predictive value of exercise electrocardiography (Ex ECG) or exercise radionuclide studies (Ex RNU) was 61.7 and 68.4 per cent respectively. DM, post-menopausal state and LDL/HDL ratio more than 3 were significant risk factors in women.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1894298 TI - Immunological alterations following open heart surgery. AB - Immunological changes in thirty patients undergoing various cardiac surgical procedures (twenty patients undergoing open heart surgery with either the bubble or the membrane oxygenator and ten patients undergoing closed surgical procedures) were studied. There was an activation of suppressor T cells and secretion of lymphokines in patients undergoing open heart surgery with activation of the classical complement pathway. The immunological alterations were similar in all patients irrespective of the type of oxygenator used. PMID- 1894299 TI - Role of circulating immune complexes and platelet aggregation in the development of experimentally induced atherosclerosis in monkeys with normal intact vas deferens and following vasectomy. AB - The study was undertaken in normal and vasectomized monkeys to elucidate the relationship of circulating immune complexes and platelet aggregability with experimental aortic and coronary atherosclerosis. Four groups of animals, viz. sham-vasectomized stock diet fed, vasectomized stock diet fed, sham-vasectomized atherogenic diet fed, were studied for a period of 1 year. An increased incidence of atherosclerosis was noted with high levels of circulating immune complexes in vasectomized monkeys. Platelets obtained from atherogenic diet fed monkeys had a clear tendency of increased aggregation and agglutination in the presence of ADP, epinephrine and ristocetin respectively. Vasectomy produced a significant enhancement in platelet aggregation response with ADP and epinephrine in atherogenic diet fed animals. The aortic and coronary atherosclerosis was also significantly increased in atherogenic diet fed groups both with and without vasectomy. PMID- 1894300 TI - Prevalence of rheumatic fever and rheumatic heart disease in school children in a rural community of the hill region of Nepal. AB - A survey of school children aged 5 to 16 years living in a rural community of the hill region of Nepal, situated about 15-22 km outside Kathmandu city, was conducted to determine the prevalence of rheumatic fever (RF) and rheumatic heart disease (RHD). Of the 4,816 eligible children enrolled in the selected schools, 4,452 (92.4%) were examined. WHO expert committee criteria (1966) was used for the diagnosis and classification of rheumatic fever. Chest x-ray, electro cardiography, echocardiography and Doppler study were done in all suspected cases of rheumatic heart disease. Six cases of RHD (1 pure mitral stenosis, 3 mitral regurgitation and 2 combined mitral stenosis and regurgitation) were identified giving overall prevalence rate of 1.35 per thousand. No case with active rheumatic fever could be identified. This is the first study on prevalence of RF/RHD in Nepal. The prevalence rate is lower than that reported from neighbouring countries. PMID- 1894301 TI - Epidemiological study of hypertension in a rural community of western Rajasthan. AB - The prevalence of hypertension was studied in a rural community of western Rajasthan comprising of 6840 subjects in the age range of 21-70 years. The overall prevalence of hypertension was 3.8 percent. It was 4.0 percent in males and 3.6 percent in females. The prevalence of hypertension increased with age in a linear fashion. PMID- 1894302 TI - Role of magnetic resonance imaging in diagnosis of aortic aneurysm presenting with compression of left pulmonary artery and left main bronchus. PMID- 1894303 TI - Electrophysiologic effects of oral propafenone in Wolff-Parkinson-White syndrome studied by programmed electrical stimulation. AB - We studied the electrophysiologic effects of oral propafenone on induction of supraventricular tachycardia (SVT) in 10 patients with Wolff-Parkinson-White syndrome (5 manifest and 5 concealed accessory pathways). Nine patients had orthodromic SVT and one patient had atrial fibrillation with preexcited QRS (shortest RR 220 msec). Electrophysiologic studies were performed during control and 48 hours after oral propafenone administered in a dose of 300 mg every eight hours. Propafenone caused complete anterograde accessory pathway conduction block in 4 of 5 patients with manifest delta waves. Retrograde conduction through the accessory pathway was abolished in 6 of 9 patients in whom it was present during control. Sustained SVT was inducible in all 9 patients during control. Propafenone prevented induction of SVT in 8 of 9 patients (88.9%) and slowed the rate of induced SVT in one patient. In the patient with atrial fibrillation (AF) the accessory pathway was blocked and AF was not inducible. There was a significant increase in the effective refractory period (ERP) of the atrium (208 +/- 40 msec to 257 +/- 25 msec, p less than 0.01), atrioventricular (AV) node (less than or equal to 256 +/- 34 msec to greater than or equal to 324 +/- 35 msec, p less than 0.001) and ventricle (204 +/- 14 msec to 262 +/- 51 msec, p less than 0.01). The atrial paced cycle length at AV nodal block also increased from 288 +/- 51 msec to 389 +/- 51 msec (p less than 0.01) after the drug. Thus propafenone has potent inhibitory effects on accessory pathways and has additional significant effects on atrial, AV nodal and ventricular refractoriness. PMID- 1894304 TI - Noncalcific stromal fissuring of stenotic valvular leaflets following balloon valvuloplasty. PMID- 1894305 TI - Aortocaval and aorto-duodenal fistulae with a leaking abdominal aortic aneurysm. PMID- 1894306 TI - Congenital complete heart block--antenatal diagnosis and management--a case report. PMID- 1894307 TI - A case of Holt Oram syndrome. PMID- 1894308 TI - A cluster of mutations in HLA-A2 alpha 2 helix abolishes peptide recognition by T cells. AB - In order to investigate the regions of HLA-A2 that control peptide-specific cytotoxic T lymphocyte (CTL) recognition, 37 HLA-A2 genes coding for 50 point mutations that span the alpha 2 helix were synthesized by the technique of saturation mutagenesis. Twenty-nine of these genes, which code for 41 point mutations, were transfected into C1R cells and used as targets in cytotoxicity assays, in the presence of influenza-A matrix peptide 58-68 with specific CTL as effectors. All the transfectants were recognized fully by matrix peptide-specific CTL apart from those with amino acid substitutions at positions 152, 154, 155, 156, or 161, which led to a total loss of recognition and those with mutations at residue 27 or a double mutation at 138 and 150, which were recognized in an intermediate manner. The clustering of the crucial residues that emerges may reflect direct interaction of their side-chains with peptide or the CTL receptor. PMID- 1894310 TI - Origins of H-2 polymorphism in the house mouse. II. Characterization of a model population and evidence for heterozygous advantage. AB - Comparison of the rate of synonymous and nonsynonymous nucleotide substitutions suggests that certain regions of the functional H-2 genes, which are part of the mouse major histocompatibility complex (Mhc), are under strong positive selection pressure. Thus far, however, little evidence has been provided for the existence of such pressure in natural mouse populations. We have, therefore, initiated experiments designed to test the hypothesis of positive selection acting on H-2 loci. The experiments are being carried out on two natural mouse populations in Jerusalem, Israel. One population occupies a space of about 100 m2 in a chicken coop, the other lives in a nearby field in which "mouse stations" providing food and shelter have been set up. Extensive typing of these two populations revealed the presence of only four H-2 haplotypes. Mice in the two populations breed continually all year around, yet population size varies seasonally, with population maxima in winter and minima in summer. The population in the chicken coop contains a relatively stable nucleus which may be organized in demes with an excess of females over males and limited territorial mobility. The rest of the mice stay in the population for a short time only and then either die or emigrate. The field population is smaller and more loosely organized than the chicken-coop population, with demes probably forming only during population maxima. For the rest of the time breeding in this population is probably panmictic. At a population minimum in the summer of 1984, H-2 homozygotes happened to predominate over heterozygotes. This situation, however, lasted for a short time only and thereafter there was a continuous, statistically highly significant increase in the proportion of H-2 heterozygotes of one or two types. The increase occurred in both populations but was more apparent in the chicken coop population. This observation provides the first experimental evidence that heterozygous advantage might be one of the mechanisms maintaining high H-2 polymorphism in natural populations of the house mouse. PMID- 1894309 TI - Limited regions of the alpha 2-domain alpha-helix control anti-A2 allorecognition: an analysis using a panel of A2 mutants. AB - The regions of the HLA-A2 molecule controlling anti-A2 alloreactivity were explored using naturally occurring allelic variants of HLA-A, and a panel of transfectants expressing the products of A2.1 genes that had been mutated at multiple positions encoding residues in the alpha 2 domain alpha-helix. As a means of detecting distant conformational effects, these altered A2.1 molecules were also examined serologically. Amino acid substitutions at the carboxy terminal end of the alpha 2 domain alpha-helix led to diminished staining with the monoclonal antibody (mAb) MA2.1. The epitope for this antibody has previously been mapped to the alpha 1 domain alpha-helix (residues 62-65). This suggests that interdomain contacts may cause conformational alteration, and that mutants can have distant, as well as local effects. Of the 24 positions where substitutions were made, only six led to loss of the anti-A2 alloresponse by the three clones and three lines that were tested. In addition, the mutations that altered the MA2.1 epitope, located on the alpha 1 domain alpha-helix, did not inhibit allorecognition. This suggests that a limited number of regions on the A2.1 molecule are responsible for allodeterminant expression. The most influential substitutions were those at positions 152, 154, 162, and 166. It is notable that three of these are predicted to be T-cell receptor (Tcr)-contacting residues, and one (152) to contribute to peptide binding. These results suggest that the specificity of alloreactive T cells is determined by exposed polymorphisms, directly contacted by the Tcr, and by concealed polymorphisms which influence peptide binding. PMID- 1894311 TI - A novel and rapid cloning method for the T-cell receptor variable region sequences. AB - Conventional polymerase chain reactions (PCR) require sequence information on both ends of the DNA to be amplified. The novel technique described here allows the amplification of cDNA fragments with sequence information from one end only. Blunt-ended double-strand cDNA is prepared, circularized with T4 DNA ligase and used as a PCR template. The two PCR primers are designed to hybridize to the known region in an outward orientation allowing the amplification of the unknown sequence. The method was established using the alpha-chain of T-cell antigen receptors (Tcr) as an example. The cDNA synthesized from 1 microgram of total RNA from human peripheral lymphocytes was amplified and cloned resulting in a library of 1-2 x 10(6) Tcr-specific clones. The method should also be useful for cloning full-length cDNA or for the identification of new members of a gene family that share a conserved domain. PMID- 1894312 TI - Segmental exchange between MHC class I genes in a higher primate: recombination in the gorilla between the ancestor of a human non-functional gene and an A locus gene. AB - Classical human major histocompatibility complex (MHC) class I molecules are the products of highly diverse gene loci. It has been suggested that segmental exchange may play a role in the generation of diversity at the antigen recognition site of MHC class I molecules. Here we present the cloning, sequencing and expression of two gorilla A locus cDNAs. One of these cDNAs shows remarkable similarity to the non-functional HLA-AR locus gene (5.4-LBF) only in exon 2. The remainder of the cDNA, however, is most closely related to other classical higher primate A locus genes. This suggests that a segmental exchange may have occurred between the ancestor of the non-functional HLA-AR gene and a classical gorilla A locus gene. Furthermore, the recombination event resulting in Gogo-A3 has affected its antigen recognition site. These data, therefore, demonstrate that segmental exchange can generate diversity at the antigen recognition sites of primate MHC class I molecules and suggest that non functional genes can contribute to the generation of diversity of classical MHC class I genes. PMID- 1894313 TI - Recognition of HLA-B27 by mouse cytotoxic T-cell clones: a transgenic mouse model. AB - As a basis for the characterization of mouse T cells involved in the recognition of xenogeneic HLA molecules, a panel of HLA-B27-reactive cytotoxic T-cell clones was generated upon stimulation by cells from HLA-B27-transgenic mice. The HLA-B27 induced T-cell response was found to comprise two categories of clones: some recognizing HLA-B27 independent of H-2 molecules expressed by the target cells (unrestricted clones), others recognizing HLA-B27 in an H-2-restricted manner. The unrestricted clones exhibited diverse specificities, as judged from their various cross-reactivities with other xenogeneic (HLA) or allogeneic (H-2) molecules. In addition, although most of the unrestricted clones were able to react with both mouse and human HLA-B27-transgenic mice. The HLA-B27-induced T cell which reacted only with HLA-B27-positive mouse, and not human cells. These findings illustrate that both H-2-restricted and unrestricted T cells with diverse specificities contribute to HLA-B27-xenorecognition. PMID- 1894314 TI - The rat RT.BM1 MHC class I cDNA shows a high level of sequence similarity to the mouse H-2T23d gene. PMID- 1894315 TI - Cancer registration: principles and methods. PMID- 1894316 TI - Cancer registration: principles and methods. Quality and quality control. PMID- 1894317 TI - Cancer registration: principles and methods. Reporting of results. PMID- 1894318 TI - Cancer registration: principles and methods. Statistical methods for registries. PMID- 1894319 TI - Cancer registration: principles and methods. Analysis of survival. PMID- 1894320 TI - The hospital-based cancer registry. PMID- 1894321 TI - Cancer registration in developing countries. PMID- 1894322 TI - Cancer registration: legal aspects and confidentiality. PMID- 1894323 TI - Cancer registration: principles and methods. Editing for consistency of data items. PMID- 1894324 TI - Planning a cancer registry. PMID- 1894325 TI - The Danish Cancer Registry, a self-reporting national cancer registration system with elements of active data collection. PMID- 1894326 TI - The Thames Cancer Registry. PMID- 1894327 TI - Cancer registration in Ontario: a computer approach. PMID- 1894328 TI - The Department of Health--Rizal Cancer Registry. PMID- 1894329 TI - CANREG: cancer registration software for microcomputers. PMID- 1894330 TI - Cancer registration: principles and methods. Data sources and reporting. PMID- 1894331 TI - History of cancer registration. PMID- 1894332 TI - Cancer registration: principles and methods. Items of patient information which may be collected by registries. PMID- 1894333 TI - Cancer registration: principles and methods. Classification and coding of neoplasms. PMID- 1894334 TI - Purposes and uses of cancer registration. PMID- 1894335 TI - Manual and computerized cancer registries. PMID- 1894336 TI - Pterygium and dry eye--a clinical correlation. AB - Schirmer's test and tear film break-up time (BUT) were studied in 56 eyes of patients with pterygium and compared with 50 eyes of normal healthy subjects representing the same age, sex and geographical distribution. Both the values were found to be significantly reduced in cases of pterygium indicating the inadequacy of tear film in these patients. PMID- 1894337 TI - Role of proteins and cholesterol in human senile cataractogenesis. AB - Cataracts are a major cause of blindness in man with far reaching personal, social and economic consequences. The clarity of the lens is dependent upon the maintenance of the integrity of the fiber cell plasma membrane whose important component is cholesterol. In the present study, we have demonstrated that cataract formation influences the cholesterol and protein distribution within the lens. PMID- 1894338 TI - Role of radiation therapy in the treatment of benign ocular diseases. AB - Radiation therapy, although a prime treatment modality for malignant disease, has few definitive indications for some benign ocular diseases too. Orbital pseudotumour, Graves ophthalmopathy and pterygium are the conditions where the radiation oncologist has got an important role to play. This article reviews the current status of the role of radiation and its effectiveness in the management of these diseases. PMID- 1894339 TI - Visual evoked potentials in optic nerve injury--does it merit to be mentioned? AB - The value of Visual Evoked Potentials (VEP) in the management of indirect optic nerve injury was prospectively studied in 78 patients. The initial VEPs were normal in 10, abnormal in 29 and absent in 39 patients. All 10 patients with normal VEP showed visual recovery. Amongst 29 patients with abnormal VEP, 26 (86.6%) showed improvement. In 39 patients initial VEPs showed no wave, however, subsequent VEP recordings demonstrated wave formation. Thus in 31 patients repeated VEP recordings failed to demonstrate wave formation, and none of them improved. This study, thus brings out the high predictive value of both positive and negative VEPs. PMID- 1894340 TI - Conjunctival impression cytology in dry eye states. AB - Impression cytology technique was used to study the cytological changes of in 30 patients with various diseases (Xerophthalmia, Steven-Johnson's syndrome, trachoma, alkali burns, kerato conjunctivitis sicca) resulting in dry eye syndrome. The main features of impression cytology were squamous metaplasia of epithelial cells and altered goblet cell density. The comparison between conjunctival biopsy findings and impression cytology confirm that impression cytology provides the same information as that of biopsy. Hence, the authors advocate that this non-invasive simple technique can replace conjunctival biopsy in confirmation of diagnosis in dry eye syndrome. PMID- 1894341 TI - Corneal endothelial changes following pars plana lensectomy. AB - The corneal endothelial status was studied in 40 eyes of patients with congenital cataract before and 3 months after surgery. Twenty eyes of patients who underwent pars plana lensectomy revealed a mean endothelial cell loss of 8% (SD +/- .76) while the remaining 20 eyes which were operated by needling aspiration had a endothelial cell loss of 10% (SD +/- .89). The difference between the two groups was not statistically significant. PMID- 1894342 TI - Giant aneurysm of internal carotid artery presenting features of retrobulbar neuritis. AB - We report the case of a man who presented with in the features of left optic nerve compression. CT scan and carotid angiography demonstrated an unruptured giant aneurysm of the left internal carotid artery possibly kinking the optic nerve. Carotid ligation in the neck saved both life and vision. PMID- 1894343 TI - Posterior keratoconus due to iron nail injury--a case report. AB - A case of post-traumatic keratoconus is presented. This is an unusual variant of an uncommon disorder. Posterior keratoconus is a very rare ectatic dystrophy of the cornea. Since its first description in 1927, only a few cases have been described in the literature. Posttraumatic posterior keratoconus is a much rarer entity. We are reporting a case of posterior keratoconus caused by iron nail injury. PMID- 1894344 TI - Orbital lymphangiomatoid malformation--a case report. PMID- 1894345 TI - Leiomyoma of the orbit. AB - A rare case of leiomyoma located anteroinferiorly in the orbit of a 39-year-old male patient is reported. The histopathogenesis and management is discussed. PMID- 1894346 TI - Flute handle for controlled suction in double cannula aspiration. PMID- 1894347 TI - Malignant tumours of the eye and adnexa. AB - We analysed 262 consecutive histopathologically proved cases of malignant tumours of the eye and its adnexa seen over a nine year period. Two peaks were observed in the age distribution one in the first decade due to retinoblastoma and another between forty one to sixty years due to malignant lid tumours especially meibomian carcinoma. Males (56%) were affected more often. Intraocular tumours (34%) formed the commonest group of malignant orbito-ocular tumours; lacrimal gland tumours (3%) occurred least frequently. Of the individual tumours, retinoblastoma (32%) was seen most often followed by squamous cell carcinoma (25%). The frequency of meibomian gland carcinoma in Madras was significantly more than in North India. Extra-ocular malignant melanomas out-numbered intraocular (uveal) malignant melanomas. The significance of these observations is discussed. PMID- 1894348 TI - Benign ocular manifestations of sickle cell anemia in Arabs. AB - A complete ophthalmic examination was carried out for each of 54 adult patients with various forms of sickle cell disease. Mild and infrequent signs in the anterior and posterior segments were found, but there were no cases of proliferative sickle cell retinopathy detected. These findings were compared with the reported findings in the black Americans of African origin with the same disease. The probable explanations were the high prevalence of fetal haemoglobin in Arab sicklers, the rarity of sickle cell disease among the Arabs and the possible existence of a different gene. PMID- 1894350 TI - Proteus mirabilis urease: use of a ureA-lacZ fusion demonstrates that induction is highly specific for urea. AB - Proteus mirabilis, a common agent of nosocomially acquired and catheter associated urinary tract infection, is the most frequent cause of infection induced bladder and kidney stones. Urease-catalyzed urea hydrolysis initiates stone formation in urine and can be inhibited by acetohydroxamic acid and other structural analogs of urea. Since P. mirabilis urease is inducible with urea, there has been some concern that urease inhibitors actually induce urease during an active infection, thus compounding the problem of elevated enzyme activity. Quantitating induction by compounds that simultaneously inhibit urease activity has been difficult. Therefore, to study these problems, we constructed a fusion of ureA (a urease subunit gene) and lacZ (the beta-galactosidase gene) within plasmid pMID1010, which encodes an inducible urease of P. mirabilis expressed in E. coli JM103 (Lac-). The fusion protein, predicted to be 117 kDa, was induced by urea and detected on Western blots (immunoblots) with anti-beta-galactosidase antiserum. Peak beta-galactosidase activity of 9.9 mumol of ONPG (o-nitrophenyl beta-D-galactopyranoside) hydrolyzed per min per mg of protein, quantitated spectrophotometrically, was induced at 200 mM urea. The uninduced rate was 0.2 mumol of ONPG hydrolyzed per min per mg of protein. Induction was specific for urea, as no structural analog of urea (including acetohydroxamic acid, hydroxyurea, thiourea, hippuric acid, flurofamide, or hydroxylamine) induced fusion protein activity. These data suggest that induction by inactivation of UreR, the urease repressor protein that governs regulation of the urease operon, is specific for urea and does not respond to closely related structural analogs. PMID- 1894349 TI - Effects of immunization with Porphyromonas gingivalis and Prevotella intermedia on progression of ligature-induced periodontitis in the nonhuman primate Macaca fascicularis. AB - The nonhuman primate (Nhp) has proven to be a useful model of human periodontitis. This study describes the immunological characteristics of this model and the ability of active immunization to interfere with ecological changes in the microbiota and its associated disease symptoms. Nhps were parenterally immunized with whole-cell antigens of Porphyromonas gingivalis and Prevotella intermedia. The immunization elicited an approximate 2-log increase in serum immunoglobulin G (IgG), IgM, and IgA isotype antibody that was highly specific for these immunogens. Postimmunization and postligation, there was minimal change in the levels of specific antibody. P. gingivalis immunization significantly inhibited the emergence of this species during disease progression. In contrast, induction of anti-P. intermedia antibody had a minimal effect on this species within the subgingival plaque. Plaque indices showed few changes that could be attributed to active immunization. Both bleeding on probing and loss of attachment were higher in ligated sites of immunized animals than in the placebo treated group. A significant increase in bone density loss was observed in the ligated teeth from immunized versus control animals. These findings indicate that active immunization of Nhps can elicit a substantial systemic immune response; however, while this response may effect the emergence of an individual microorganism, it appears that other ecological considerations are critical in disease progression. It is also possible that the induction of a broad-based immune response to multiple bacterial antigens can result in increased disease, potentially associated with hypersensitivity reactions to the bacteria in the subgingival plaque. PMID- 1894351 TI - Specific T-cell response to a Pneumocystis carinii surface glycoprotein (gp120) after immunization and natural infection. AB - T cells have been shown to be important in recovery from Pneumocystis carinii pneumonitis, although no specific antigen of P. carinii has been defined as containing T-cell epitopes. P. carinii has an abundant mannosylated surface glycoprotein of approximately 120 kDa (gp120) which induces a prominent host antibody response in experimental animals after exposure to P. carinii in the environment or after recovery from P. carinii pneumonitis. P. carinii gp120 was purified from infected lungs by lectin affinity chromatography. Standard in vitro lymphocyte stimulation assays using purified gp120 and control normal lung preparations were performed on isolated T cells obtained from BALB/c mice after immunization with P. carinii-infected crude lung homogenates or lectin-purified gp120. Lymphocytes from reconstituted severe combined immunodeficient mice which had recovered from naturally acquired P. carinii pneumonitis were also tested. A specific T-cell response was elicited by gp120 after immunization with P. carinii gp120 and after recovery from P. carinii pneumonitis. In addition, the mice developed a strong antibody response to gp120 as ascertained by Western blot (immunoblot). These data suggest that gp120 may be important in the recognition of P. carinii by T cells. PMID- 1894352 TI - Pathogen-related oral spirochetes from dental plaque are invasive. AB - Spirochetes that share pathogen-restricted antigens with Treponema pallidum subsp. pallidum have been identified in dental plaque and diseased gingival tissues, but it is not known whether these spirochetes possess virulence characteristics. In this study, plaque spirochetes were able to transmigrate a tissue barrier in vitro and were identified on the other side by using monoclonal antibodies specific for pathogen-restricted determinants from T. pallidum subsp. pallidum. This invasive capability is shared with T. pallidum subsp. pallidum, but cultured oral and intestinal treponemes did not perforate the tissue barrier. Cocultures indicated that invasive treponemes do not create opportunities for cultivable oral treponemes to cross the barrier. These findings indicate that gingival tissues may be a port of entry for previously unrecognized invasive spirochetes in humans. PMID- 1894353 TI - Activation of human peripheral blood mononuclear cells by interleukin-2 and granulocyte-macrophage colony-stimulating factor to inhibit Cryptococcus neoformans. AB - The abilities of selected cytokines to activate human peripheral blood mononuclear cells (PBMC) to inhibit and kill the opportunistic fungus Cryptococcus neoformans were studied. PBMC were cultured for 7 days in cell wells containing no cytokines, tumor necrosis factor (TNF), gamma interferon (IFN gamma), 1,25-dihydroxycholecalciferol (vitamin D3), granulocyte-macrophage colony stimulating factor (GM-CSF), or interleukin-2 (IL-2) and were then challenged for 24 h with a fixed number of CFU of C. neoformans. The number of CFU increased in wells containing no cytokines, TNF, IFN-gamma, or vitamin D3 and remained about the same in wells containing GM-CSF. In contrast, the number of CFU in wells containing IL-2-stimulated PBMC decreased, suggesting fungicidal activity. Optimal conditions for IL-2 stimulation included a minimum of 5 days of incubation of PBMC with IL-2, a concentration of 100 U of IL-2 per ml, and a high ratio of effectors to fungi. Separation of IL-2-stimulated PBMC based upon their adherence to plastic revealed that antifungal activity resided in the nonadherent fraction. These data demonstrate that IL-2 and GM-CSF are capable of stimulating PBMC-mediated antifungal activity and suggest that these cytokines may play physiological or pharmacological roles in host defenses against cryptococcosis. PMID- 1894354 TI - Contribution of the B oligomer to the protective activity of genetically attenuated pertussis toxin. AB - An enzymatically deficient recombinant S1 subunit, in which Arg-9 was replaced by Lys, was combined with native B oligomer to form a mutant holotoxin molecule. This molecule exhibited decreased leukocytosis-promoting and histamine sensitizing activities compared with those of the native toxin, supporting the view that the B oligomer is not responsible for these activities. The protective activity of this genetically attenuated pertussis toxin was compared with that of B oligomer alone. The mutant pertussis toxin and B oligomer were similarly capable of protecting mice against a respiratory infection with Bordetella pertussis, suggesting that the B oligomer makes a significant contribution to the protection afforded by the genetically attenuated holotoxin. PMID- 1894355 TI - Salivary-agglutinin-mediated adherence of Streptococcus mutans to early plaque bacteria. AB - Interspecies binding is important in the colonization of the oral cavity by bacteria. Streptococcus mutans can adhere to other plaque bacteria, such as Streptococcus sanguis and Actinomyces viscosus, and this adherence is enhanced by saliva. The salivary and bacterial molecules that mediate this interaction were investigated. Salivary agglutinin, a mucinlike glycoprotein known to mediate the aggregation of many oral streptococci in vitro, was found to mediate the adherence of S. mutans to S. sanguis or A. viscosus. Adherence of S. mutans to saliva- or agglutinin-coated S. sanguis and A. viscosus was inhibited by antibodies to the bacterial agglutinin receptor. Expression of the S. sanguis receptor (SSP-5) gene in Enterococcus faecalis increased adhesion of this organism to saliva- or agglutinin-coated S. sanguis and A. viscosus. This interaction could be inhibited by antibodies to the agglutinin receptor. The results suggest that salivary agglutinin can promote adherence of S. mutans to S. sanguis and A. viscosus through interactions with the agglutinin receptor on S. mutans. PMID- 1894356 TI - Ability of recombinant or native proteins to protect monkeys against heterologous challenge with Plasmodium falciparum. AB - To circumvent problems associated with polymorphic vaccine candidates for Plasmodium falciparum malaria, we evaluated recombinant proteins representing sequences from relatively high conserved regions of the precursor to the major merozoite surface proteins, gp190, for their ability to protect Saimiri monkeys against malaria challenge. Recombinant proteins represented amino acid residues 147 to 321 (p190-1) or 147 to 321 and 1060 to 1195 (p190-3), and their efficacy was compared with that of native gp190 and its processed products. All antigens were derived from P. falciparum K1, a Thai isolate, while the challenge strain was Palo Alto (from Uganda, Africa), which contains, with the exception of the N terminal 375 amino acids, which are almost identical to the K1 sequence, essentially the MAD-20 allelic form of gp190. By 12 days following challenge, each control monkey required drug treatment. Three monkeys injected with p190-3 required therapy, while one cleared the parasites without therapy. Two monkeys injected with p190-1 received therapy on day 14, while the remaining two cleared the parasites without therapy. Of four animals injected with native gp190, because of health reasons unrelated to malaria, one was not challenged with parasites and one was removed from the study 8 days after challenge when its parasitemia was 1.1% (parasitemias in control animals ranged from 4.3 to 9%); the remaining two cleared the parasites after maximum parasitemias of 0.45 and 0.53%. The highest levels of antiparasite antibody were produced by animals immunized with native gp190. There was a significant correlation between monkeys which did not require drug treatment and antiparasite antibody. These results may suggest that native gp190 and/or its processed products can provide excellent protection against heterologous challenge and that antibody is important for protection. The challenge for vaccine development is to identify the protective sequence(s). PMID- 1894357 TI - Effect of carrier priming on immunogenicity of saccharide-protein conjugate vaccines. AB - Previous studies with saccharide-protein conjugates have demonstrated that antibody responses to the saccharide can be improved by the preexistence of carrier immunity. Here we report that prior exposure to the carrier protein can either enhance or suppress antibody response to polysaccharides administered in saccharide-protein conjugates. A dose-dependent role for carrier priming in the antisaccharide antibody response to three saccharide-protein conjugate vaccines, i.e., a Streptococcus pneumoniae type 4 polysaccharide-tetanus toxoid (TT) conjugate (PS4TT), a Neisseria meningitidis group C polysaccharide-TT conjugate (MenCTT), and a N. meningitidis group C oligosaccharide-diphtheria mutant toxin conjugate (MenCCRM), was investigated. The results showed that an increase in the antipolysaccharide antibody response could be obtained for both PS4TT and MenCTT but not for MenCCRM with low-dose carrier priming (0.025 to 0.25 microgram). However, suppression of the antipolysaccharide antibody response was observed with the PS4TT and MenCTT vaccines with high-dose (25-micrograms) carrier priming. There was no suppression effect with MenCCRM. The increase in the antipolysaccharide antibody response was shown to be restricted to the immunoglobulin G1 (IgG1) subclass, whereas suppression with high-dose carrier priming affected all antipolysaccharide subclass antibodies induced by PS4TT (IgG1, IgG2b, and IgG3) and only two of the four subclass antibodies induced by MenCTT (IgG2a and IgG2b). The increase in the antipolysaccharide antibody response was also present at the antipolysaccharide IgM antibody level but was not observed at the anti-carrier IgG antibody level. PMID- 1894358 TI - Suppression by Trypanosoma brucei rhodesiense of the capacities of human T lymphocytes to express interleukin-2 receptors and proliferate after mitogenic stimulation. AB - We studied the suppressive effects induced in phytohemagglutinin (PHA)-stimulated human peripheral blood mononuclear cells (PBMC) by purified blood forms of Trypanosoma brucei rhodesiense. The parasite was found to markedly impair lymphocyte proliferation (measured in terms of [3H]thymidine incorporation). The extent of this effect increased with parasite concentration and was not due to mitogen absorption, depletion of medium nutrients, or PBMC killing by the parasite. Significant reductions in interleukin-2 receptor (IL-2R) expression, determined by flow cytometric analysis, were also observed in PHA-stimulated PBMC cultured in the presence of T. b. rhodesiense as evidenced by marked decreases in the surface density of the receptor. Concomitant decreases in the percentage of IL-2R+ cells were recorded in approximately half of the experiments. A discrete, dimly stained subpopulation of IL-2R+ cells were consistently demonstrable whether or not a reduction in the percentage of IL-2R+ cells occurred. Living, but not glutaraldehyde-fixed, parasites suppressed IL-2R expression. In kinetic studies, a low but reproducible level of suppression of IL-2R was demonstrable as early as 6 h after PHA stimulation; the extent of this effect became considerably more pronounced as additional culture time elapsed. Levels of IL-2 biological activity in cocultures of T. b. rhodesiense with PHA-stimulated PBMC were comparable with or higher than those present in control cultures lacking the parasite. Therefore, insufficient levels of this cytokine would be an unlikely explanation for the noted suppression of IL-2R expression and lymphoproliferation. These effects of T. b. rhodesiense could represent an important component of the mechanism by which immunosuppression develops in African sleeping sickness. PMID- 1894359 TI - Molecular characterization of the humoral response to the 41-kilodalton flagellar antigen of Borrelia burgdorferi, the Lyme disease agent. AB - The earliest humoral response in patients infected with Borrelia burgdorferi, the agent of Lyme disease, is directed against the spirochete's 41-kDa flagellar antigen. In order to map the epitopes recognized on this antigen, 11 overlapping fragments spanning the flagellin gene were cloned by polymerase chain reaction and inserted into an Escherichia coli expression vector which directed their expression as fusion proteins containing glutathione S-transferase at the N terminus and a flagellin fragment at the C terminus. Affinity-purified fusion proteins were assayed for reactivity on Western blots (immunoblots) with sera from patients with late-stage Lyme disease. The same immunodominant domain was bound by sera from 17 of 18 patients. This domain (comprising amino acids 197 to 241) does not share significant homology with other bacterial flagellins and therefore may be useful in serological testing for Lyme disease. PMID- 1894360 TI - Characterization of the 35-kilodalton Treponema pallidum subsp. pallidum recombinant lipoprotein TmpC and antibody response to lipidated and nonlipidated T. pallidum antigens. AB - The gene encoding the 35-kDa immunogenic Treponema pallidium subsp. pallidum (T. pallidum) membrane protein C, TmpC, was cloned, sequenced, and expressed in Escherichia coli. The deduced amino acid sequence carries on N-terminal signal sequence with a four-amino-acid motif, which is characteristic for bacterial lipoproteins. Metabolic labeling with radioactive palmitic acid of E. coli expressing TmpC revealed incorporation of the fatty acid into the antigen. The antigen was overproduced, purified to near homogeneity and used in an enzyme linked immunosorbent assay (ELISA) to evaluate its potential for the serodiagnosis of syphilis. Although all sera from untreated secondary syphilis patients were reactive in this TmpC ELISA, only a minority of the serum samples from untreated patients in the primary or early latent stage of the disease contained significant anti-TmpC antibodies. To study the influence of the lipid moiety on the antigenic properties of the TmpC, TmpA, and TpD lipoproteins, plasmids encoding nonlipidated forms of these antigens were constructed. In addition, a plasmid expressing a lipidated form of the otherwise non-lipid modified antigen TmpB was constructed. Immunization and absorption experiments with these lipidated and nonlipidated antigens showed that antibodies against the lipid moiety of lipoproteins could not be detected on immunoblots, neither in sera from infected rabbits nor in sera from animals immunized with the lipoproteins. In addition, we were unable to demonstrate cross-reactivity between antibodies against the T. pallidum lipoproteins and those reactive to the Venereal Diseases Research Laboratories test, suggesting that antibodies reactive to the Venereal Diseases Research Laboratories test are unrelated to antilipoprotein antibodies. PMID- 1894361 TI - Antimalarial antibodies of the immunoglobulin G2a isotype modulate parasitemias in mice infected with Plasmodium yoelii. AB - Previous studies have demonstrated the importance of antibodies in mediating immunity to malaria, but the relative contribution of the different immunoglobulin isotypes has not been assessed. In this study, hyperimmune plasma was generated against Plasmodium yoelii and separated by protein A-Sepharose chromatography into fractions containing immunoglobulin G1 (IgG1), IgG2a, IgG2b, or IgG3 antibodies and the remaining nonbinding plasma proteins, including IgM. Following concentration, the antimalarial titer of each isotypic fraction was approximately equivalent to the corresponding isotype in hyperimmune plasma. The isotypic fractions were passively transferred to BALB/c and outbred ICR mice prior to challenge with virulent P. yoelii 17XL and to CBA/CaJ mice challenged with avirulent P. yoelii 17XNL. Only mice receiving IgG2a antibodies experienced an altered course of infection. Immunoprecipitation studies showed that all four IgG isotypes appear to recognize a similar set of antigens. These results suggest that antimalarial antibodies of the IgG2a isotype play a dominant role in modulating P. yoelii parasitemias. PMID- 1894362 TI - Construction and expression of plasmids containing mutated diphtheria toxin A chain-coding sequences. AB - We previously demonstrated that cells can be killed through transfection of an expression plasmid that encodes the diphtheria toxin A-chain fragment (DT-A). This report describes the construction of expression plasmids containing three mutant DT-A-coding sequences substituting glutamic acid 148 with aspartic acid, serine, or glutamine which are known to have 100- to 300-fold-reduced ADP ribosylation activity measured in vitro. The toxicity of these constructs was determined in cotransfection experiments using HeLa and 293 cells with a luciferase expression plasmid as the reporter. Dose responses were compared for the three new DT-A mutant plasmids and for the corresponding plasmids containing wild-type DT-A and the previously characterized tox 176 mutant. The dose required to produce 50% inhibition of control luciferase expression in 293 embryonic kidney cells for the five plasmids ranged from 0.01 micrograms for wild-type DT-A to 1.2 micrograms for the least toxic plasmid, which replaces glutamic acid 148 with glutamine. In conclusion, a wide range of DT-A toxicity can be achieved by using plasmid expression vectors that encode different DT-A mutations. PMID- 1894363 TI - Alterations in cysteine proteinase content of rat lung associated with development of Pneumocystis carinii infection. AB - The rate of hydrolysis of three cysteine-type proteinase substrates, N benzyloxycarbonyl-Arg-Arg-4-methyl-7-coumarylamide (AMC) (cathepsin B), Arg-AMC (cathepsin H), and N-benzyloxycarbonyl-Phe-Arg-AMC (cathepsin L), were determined in rat lung throughout the time course of the induction of Pneumocystis carinii infection by immunosuppression. Cathepsin B-like and cathepsin L-like activities fell below control values initially, but from week 8 of the immunosuppressive treatment significant increases above the control were noted. Cathepsin H-like activity was greater than control levels from week 3, and by week 12 it was 7,600% of the mean control value. When compared with the relative degree of infection, as assessed from the number of cysts present in lung impression smears, cathepsin B-like and cathepsin L-like activities were significantly increased only at heavy parasite burdens while cathepsin H-like activity displayed a close correlation with parasite number (r = 0.884; P less than 0.001). Activity was detected in lysates of purified P. carinii with all three substrates. Treatment of heavily infected animals with co-trimoxazole cleared the lungs of P. carinii, and this was accompanied by a marked reduction in proteinase activity, in particular, cathepsin H-like activity, which fell from 108- to 3 fold the mean control value following drug treatment. Analysis of cathepsin H isozyme patterns by fluorography following isoelectric focusing revealed differences between treated and control lung samples. In the immunosuppressed group, there was a time-dependent increase in the intensity of some of the bands observed in the controls and an appearance of several novel bands which corresponded to bands observed in lysates of P. carinii. It is likely, therefore, that the increased proteinase activity observed in the treated group is due, at least in part, to isozymes from P. carinii; consequently, cathepsin H-like activity might be of use diagnostically in the identification of P. carinii infection and in the estimation of parasite burden. PMID- 1894364 TI - Subclass distribution of salivary secretory immunoglobulin A antibodies to oral streptococci. AB - The ability of specific secretory immunoglobulin A (S-IgA) antibodies to inhibit bacterial colonization of mucosal surfaces may be neutralized by the activity of bacterial IgA1 proteases. Because of the resistance of the IgA2 subclass to these enzymes, the biological effect of IgA1 proteases in vivo may depend on the subclass distribution of the bacterium-specific antibodies. We have estimated the subclass distribution of S-IgA antibodies in saliva samples from 13 individuals against IgA1 protease-producing (Streptococcus sanguis and Streptococcus oralis) and nonproducing (Streptococcus gordonii and Streptococcus mitis bv. 2) oral streptococci. IgA1 was found to be the predominant subclass of antibodies against these four bacteria in most of the saliva samples, corroborating previous data suggesting a role of IgA1 proteases in plaque formation. However, variation in the subclass distribution of S-IgA antibodies against the same strain was observed. In one individual, IgA2 was the predominant subclass of antibodies against all four streptococci and of total salivary S-IgA, pointing to the possible significance of genetic variations. The study also addresses methodological problems related to the quantitation of salivary antibodies by solid-phase immunoassays. PMID- 1894365 TI - Experimental model of atrophic rhinitis in gnotobiotic pigs. AB - To study the pathogenesis of atrophic rhinitis, gnotobiotic pigs (n = 6) were inoculated intranasally with a sterile sonicate of a toxigenic strain of Bordetella bronchiseptica (0.16 mg of protein per ml) at 5 days of age, and they were then inoculated intranasally with 1 ml (5,250 CFU/ml) of a live, toxigenic strain of Pasteurella multocida at 7 days of age. Pigs were necropsied at 2, 5, 9, 14, 21, and 28 days postinoculation; those pigs necropsied after 5 days had developed turbinate atrophy. Other gnotobiotic pigs received the following inoculation protocols: (i) a sterile sonicate of a nontoxigenic strain of B. bronchiseptica (0.2 mg of protein per ml), followed by toxigenic P. multocida (n = 4); (ii) toxigenic P. multocida alone (n = 7); (iii) diluent (sterile tryptose broth) (n = 2); (iv) the sterile sonicate of toxigenic B. bronchiseptica alone (n = 2); or (v) the sterile sonicate of a nontoxigenic strain of B. bronchiseptica alone (n = 2). Turbinate atrophy did not occur in the latter groups except for one pig inoculated with only toxigenic P. multocida. These studies show that turbinate atrophy occurs in pigs given the toxigenic B. bronchiseptica sonicate and then given live, toxigenic P. multocida. This experimental regimen is a useful model for (i) studying the pathogenesis of atrophic rhinitis and (ii) testing vaccine strategies. PMID- 1894366 TI - Tumor necrosis factor and interleukin-1 activities in free lung cells after single and repeated inhalation of bacterial endotoxin. AB - Bacterial endotoxins (lipopolysaccharides), important components of many organic dusts, are known to induce macrophages to produce the inflammatory mediators interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF-alpha). To investigate the role of these mediators in the early inflammatory responses in the lung, guinea pigs were exposed to an aerosol of bacterial endotoxin. A bronchoalveolar lavage (BAL) was then performed, and TNF-alpha and IL-1 in lysed BAL cells and in the supernatants from BAL cell cultures were studied. The effect of single and repeated LPS inhalation exposures on the activities of TNF and IL-1 was studied, as was the effect of LPS added to the cell culture medium. A single inhalation exposure to LPS caused an increase in the TNF-alpha and IL-1 activities in cell lysate and in the cell culture supernatant. After a second inhalation exposure, cell-associated and extracellular TNF-alpha activity could not be detected, whereas IL-1 activity was markedly enhanced. IL-1 activity was increased when LPS was added to the cell culture medium with or without a prior inhalation exposure. In contrast, TNF-alpha activity was not affected after a second exposure. PMID- 1894367 TI - Protection of rat intestine against cholera toxin challenge by monoclonal anti idiotypic antibody immunization via enteral and parenteral routes. AB - A mouse monoclonal anti-idiotypic (anti-id) immunoglobulin M (IgM) antibody, called MAb2, was raised against a mouse monoclonal anti-cholera toxin (anti-CT) antibody (MAb1). The MAb2 was shown, by competition with CT for MAb1, to bear the internal image of an epitope of CT. MAb2 immunization of rats was performed via the intraperitoneal, intragastric, and intrajejunal routes and compared with immunization of rats with either a control, isotype- and allotype-matched MAb or with CT via the same routes. Both serum IgG and bile IgA anti-CT Ab3's were detected by enzyme-linked immunosorbent assay in anti-id MAb2-immunized rats, although their titers were lower than those in CT-immunized rats. No anti-CT antibodies were detected in sera and bile of rats immunized with the control MAb. When tested for degree of gut protection against a CT challenge, rats immunized with MAb2 by the intrajejunal route showed a rather high degree of protection, which was only slightly lower than that of rats immunized with CT via the same route; all rats but one immunized with the control MAb were unprotected. There was, however, no correlation between serum or bile anti-CT titers and degree of gut protection in MAb2-immunized rats. Their serum anti-CT Ab3's were purified by adsorption and elution from a CT immunosorbent and resembled anti-CT MAb1 in their unique reactivity with MAb2. This constitutes to our knowledge the second report of protection against a pathogen by anti-id immunization via the enteric route. PMID- 1894368 TI - Treponema phagedenis encodes and expresses homologs of the Treponema pallidum TmpA and TmpB proteins. AB - We cloned and sequenced the genes from Treponema phagedenis Kazan 5 encoding proteins homologous to the TmpA and TmpB proteins of Treponema pallidum subsp. pallidum Nichols (hereafter referred to as T. pallidum). Although previous reports suggested that the TmpA and TmpB proteins were specific for T. pallidum, we found that homologs for both were expressed in T. phagedenis Kazan 5 and Reiter. The TmpA protein from T. phagedenis contained the consensus sequence that bacterial lipoproteins require for posttranslational modification and subsequent proteolytic cleavage by signal peptidase II and showed 42% amino acid sequence identity with the TmpA protein from T. pallidum. The TmpB proteins of T. phagedenis and T. pallidum had similar amino acid sequences at their amino- and carboxy-terminal ends. The central portions of both of these proteins contained four repeats of the amino acid sequence EAARKAAE. The TmpB protein from T. phagedenis had an additional amino acid sequence repeat (consensus sequence KAAKE/D) that was not found in the TmpB protein from T. pallidum; this repeat was most remarkable, as it occurred 17 times in succession. These repeated amino acid sequences probably created an extensive alpha-helix region within the TmpB proteins. As with T. pallidum, the stop codon of the T. phagedenis tmpA gene overlapped the start codon of its tmpB gene. Northern blot analysis showed that the T. phagedenis tmpA and tmpB genes were probably transcribed into a single 2.5 kb mRNA molecule. Western blot (immunoblot) analysis demonstrated that both proteins were expressed by T. phagedenis. The high degree of amino acid sequence conservation seen with the TmpA and TmpB proteins from two different Treponema species suggests that they may play crucial roles in the biology of these organisms. PMID- 1894369 TI - Inhibition of acid secretion from parietal cells by non-human-infecting Helicobacter species: a factor in colonization of gastric mucosa? AB - Helicobacter pylori has been shown to produce a protein that inhibits acid secretion from parietal cells. We have examined other non-human-infecting Helicobacter species for this property by measuring the uptake of [14C]aminopyrine into rabbit parietal cells as an indirect assessment of acid secretion. Helicobacter felis and an isolate from a rhesus monkey were shown to inhibit acid secretion. Isolates of Helicobacter mustelae gave variable responses. Whole bacteria and cell-free sonicates impaired the uptake of [14C]aminopyrine. We also tested other bacteria, including Escherichia coli, Proteus vulgaris, Klebsiella oxytoca, and Campylobacter jejuni. As whole organisms, these control bacteria had little effect on acid secretion, but sonicates caused pronounced inhibition that was partially heat labile. Pronase treatment of H. pylori destroyed its inhibitory effect. These results suggest that most Helicobacter species, but not all isolates, are able to inhibit acid secretion from rabbit parietal cells. This property may be a factor in the establishment of long-term infection by these species. PMID- 1894370 TI - Efficacy of enteric-coated protease in preventing attachment of enterotoxigenic Escherichia coli and diarrheal disease in the RITARD model. AB - In this study, we report on a novel approach based on modification of the intestinal surface to prevent diarrhea caused by enterotoxigenic Escherichia coli (ETEC). The removable intestinal tie adult rabbit diarrhea (RITARD) model was used to test the efficacy of an enteric-coated protease preparation (Detach; Enzacor Technology Pty. Ltd.) in the prevention of bacterial attachment and diarrheal disease caused by colonization factor antigen I-positive (CFA/I+) E. coli H10407. Protease was administered orally to rabbits 18 h prior to challenge with 10(11) bacteria. Four groups of rabbits were inoculated with different ETEC strains which produced different combinations of adhesin and enterotoxin or with sterile phosphate-buffered saline. Occurrence of diarrhea during the subsequent 24-h incubation period was recorded. Oral administration of protease was successful in reducing diarrhea and diarrhea-induced death in six of seven (86%) rabbits infected with CFA/I+, heat-stable and heat-labile toxin-positive E. coli (H10407). Seven of eight (87%) rabbits not protected by protease treatment died or developed severe diarrhea. Quantitative analysis of bacterial cultures obtained from the small intestine of rabbits showed a significant (P less than 0.001) 2,000-fold reduction in CFU per centimeter of intestine following treatment with protease. The efficacy of protease treatment was 99.5%, with very wide confidence limits (greater than 0 to 99.9%). The data indicate that the use of protease to prevent ETEC diarrheal disease has considerable potential. PMID- 1894371 TI - Specific and nonspecific antibody responses in different segments of the respiratory tract in rats infected with Mycoplasma pulmonis. AB - Murine respiratory mycoplasmosis resulting from Mycoplasma pulmonis infection in rats provides a useful model for the study of immunological and inflammatory mechanisms operative in the respiratory tract. We have previously shown that LEW rats develop more severe disease than do F344 rats. To further study the production of antibody responses in chronic respiratory disease due to M. pulmonis infection, we examined the distribution and development of M. pulmonis specific antibody-forming cells (AFC) in different segments of the respiratory tracts of infected LEW and F344 rats. In these studies, the upper respiratory nodes were the initial site of antibody production after infection and remained the major site for recovery of AFC. Since infected LEW rats had equal or higher numbers of AFC than did infected F344 rats, these results suggest that the level of local antibody production alone is not responsible for the decreased susceptibility of F344 rats to murine respiratory mycoplasmosis. The differences in total antibody responses appear to be due to the greater numbers of cells recovered from the tissues of infected LEW rats compared with those recovered from F344 rats, suggesting that LEW rats may have greater production of chemotactic factors. Also, we demonstrate that nonspecific activation and/or recruitment of B cells occurs in the respiratory tracts of both LEW and F344 rats after infection with M. pulmonis. PMID- 1894372 TI - Extraction, purification, and characterization of major outer membrane proteins from Wolinella recta ATCC 33238. AB - The outer membrane of Wolinella recta ATCC 33238 was isolated by French pressure cell disruption and differential centrifugation. Outer membrane proteins (OMPs) were solubilized by Zwittergent 3.14 extraction and separated by DEAE-Sephacel ion-exchange chromatography. The major OMPs that were found in W. recta ATCC 33238 and in several other Wolinella spp. consisted of proteins with apparent molecular masses of 51, 45, and 43 kDa. These three conserved proteins were purified to essential homogeneity by one- and two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and characterized chemically. Heating at between 75 and 100 degrees C revealed both the 43- and 51 kDa proteins to be heat modified from apparent molecular masses of 32 and 38 kDa, respectively. The 45-kDa protein was unmodified at all temperatures tested. Two dimensional isoelectric focusing-SDS-PAGE revealed the 51-kDa protein to be composed of multiple pIs between a pH of 5.0 and greater than 8.0 while the 43- and 45-kDa proteins had a pI of approximately 6.0. N'-terminal amino acid sequence analysis of the first 30 to 40 amino acids and search of the Protein Identification Resource data base for similar proteins only revealed the 43-kDa protein to be similar to the P.69 OMP of Bordetella pertussis; however, the homology was weak (33%). Amino acid analysis revealed the 43-kDa protein to be noncharged and the 45- and 51-kDa proteins to be hydrophilic, containing between 38 to 42% polar residues but no cysteine. This study reports the purification and partial characterization of three conserved proteins in W. recta ATCC 33238. PMID- 1894373 TI - Characterization of bradyzoite-specific antigens of Toxoplasma gondii. AB - Monoclonal antibodies that react specifically with bradyzoite antigens of Toxoplasma gondii were selected by differential immunofluorescence among hybridomas produced against these organisms. These antigens were further characterized by immunofluorescence on living bradyzoites and Western immunoblotting. Four pellicular antigens (36, 34, 21, and 18 kDa) were identified; three of these are exposed on the surface of the organism and accessible to either antibodies, trypsin cleavage, or both of these surface probing procedures. These antigens were found on recent human isolates of T. gondii, as well as on laboratory strain bradyzoites obtained from either brain cysts or in vitro-grown parasites. PMID- 1894374 TI - Purification and characterization of the heat-labile toxin of Bordetella pertussis. AB - A procedure is described for purification of pertussis heat-labile toxin (PEHLT) from cells of Bordetella pertussis. The purification procedure, performed in the cold and in the presence of protease inhibitors, gives 1,350-fold purification with yields of about 60%. The toxin was shown to be a single-chain polypeptide of 140 kDa, pI 6.02. It was completely inactivated by heating at 56 degrees C for 60 min. Rabbit antiserum prepared against PEHLT neutralized the toxin and gave a single precipitin line on immunodiffusion. In immunodiffusion assays, this anti PEHLT serum did not react with pertussis toxin, filamentous hemagglutinin, or preparations of pertussis adenylate cyclase. Purified PEHLT elicited dermonecrosis and atrophy of the spleen. PEHLT is extraordinarily active; 0.4 X 10(-12) g caused necrotic lesions in newborn mice, and with 18- to 20-g mice the 50% lethal dose was about 11 X 10(-9) g. PMID- 1894375 TI - Differential killing of Actinobacillus actinomycetemcomitans and Capnocytophaga spp. by human neutrophil granule components. AB - The purpose of this study was to determine whether granule fractions of human neutrophils differentially kill Actinobacillus actinomycetemcomitans and Capnocytophaga spp. Granule extracts were subjected to gel filtration, and seven fractions (designated A through G) were obtained. Under aerobic conditions at pH 7.0, representative strains of A. actinomycetemcomitans were killed by fraction D and variably by fraction B. In contrast, the Capnocytophaga spp. were killed by fractions C, D, F, and G. Fractions A (containing lactoferrin and myeloperoxidase) and E (containing lysozyme) exerted little bactericidal activity under these conditions. Anaerobiosis had little effect on the bactericidal activity of fractions D and F but inhibited that of fractions B and C. Electrophoresis, zymography, determination of amino acid composition, and N terminal sequence analysis revealed that fraction C contained elastase, proteinase 3, and azurocidin. Fraction D contained lysozyme, elastase, and cathepsin G. Subfractions of C and D containing elastase (subfraction C4), a mixture of elastase and azurocidin (subfraction C5), and cathepsin G (subfraction D9) were found to be bactericidal. The bactericidal effects of fraction D and subfraction D9 against A. actinomycetemcomitans was not inhibited by heat inactivation, phenylmethylsulfonyl fluoride, or N benzyloxycarbonylglycylleucylphenylalanylchloromethyl ketone. We conclude that (i) A. actinomycetemcomitans and Capnocytophaga spp. were sensitive to the bactericidal effects of different neutrophil granule components, (ii) both were sensitive to the bactericidal effects of neutral serine proteases, and (iii) the killing of A. actinomycetemcomitans by cathepsin G-containing fractions was independent of oxygen and neutral serine protease activity. PMID- 1894377 TI - Scanning and transmission electron microscopic study of adherence of Escherichia coli O103 enteropathogenic and/or enterohemorrhagic strain GV in enteric infection in rabbits. AB - The GV strain (serotype O103:H2:K-), originally isolated from a diarrheic rabbit, is an enteropathogenic Escherichia coli strain that produces diarrhea without synthesizing the classical enterotoxins and that is not invasive. This strain is characterized by a 117-kb plasmid (pREC-1). Histological study of the gut by scanning electron microscopy and transmission electron microscopy was performed on the GV strain, on a derivative strain cured of pREC-1, and on transconjugants obtained by transfer of pREC-1 to nonpathogenic strains E. coli K-12 and 6100, not belonging to the O103 serogroup. The GV strain adhered to the epithelial cells of the ileum and large intestine, whereas the cured GV strain did not. Transfer of plasmid pREC-1 to E. coli K-12 or 6100 allowed the bacteria to attach to the intestinal mucosa in the same manner as that of the wild-type GV strain. Thus, pREC-1 seems to play an important role in attachment to and colonization of the intestinal tract of rabbits by E. coli serogroup O103. Scanning electron microscopy showed numerous bacteria attached together and closely associated with intestinal villi. Transmission electron microscopy revealed effacing lesions characteristic of enteropathogenic E. coli strains: effacing of microvilli and cuplike projections (pedestal formations) associated with an acute inflammatory and hemorrhagic response. In contrast with the results reported for rabbit pathogenic O15 strains, it appeared that the Peyer's patches were not involved in the early stages of infection with the O103 GV strain. This strain may represent a model for the study of the virulence and pathogenic effects of enteropathogenic and enterohemorrhagic E. coli strains. PMID- 1894376 TI - Efficacy of a Proteus mirabilis outer membrane protein vaccine in preventing experimental Proteus pyelonephritis in a BALB/c mouse model. AB - A BALB/c mouse model of nonobstructive, ascending Proteus mirabilis pyelonephritis was characterized bacteriologically, histologically, and serologically from 3 to 28 days. Intravesicular administration of 2 X 10(8) P. mirabilis K7 resulted in the septic death of 9 (16%) of 57 mice by day 15. Among the survivors, K7 colonized the kidneys in great numbers until day 21. Histological examination of the kidneys revealed acute inflammation which was characterized by neutrophil infiltration by day 3, renal necrosis by day 7, and fibroblastic infiltration by day 14 which persisted at least until day 28. The immunoglobulin G response to the outer membrane proteins (OMP) was assessed by enzyme-linked immunosorbent assay and Western blotting (immunoblotting). Anti-OMP immunoglobulin G antibodies were detected as early as day 7, and the reciprocals of their titers rose progressively up to day 28 (i.e., greater than or equal to 500). This model was also used to assess the efficacy of OMP and lipopolysaccharide (LPS) immunization in preventing renal infection. K7 OMP or LPS (100 micrograms) preparations were administered intramuscularly in Freund's complete adjuvant. After 2 weeks, mice were intravesicularly challenged with 2 X 10(8) bacteria of the homologous K7 strain or one of four heterologous strains. Compared with the saline-immunized control group and K7 LPS-immunized mice, K7 OMP recipients were protected from death when challenged by homologous or heterologous strains. In addition, K7 OMP recipients were protected (P less than 0.003) from subsequent renal infection when challenged by the K7 strain and had more rapid bacterial renal clearance when challenged by three of four heterologous strains. OMP recipients produced antibodies which bound major OMP moieties (viz., 36- to 39-kDa cell wall constituents) as assessed by Western blotting. These results support the concept that immunization with selected bacterial protein surface coat constituents can prevent uromucosal infection by interfering with colonization or renal injury. PMID- 1894378 TI - Depletion of complement and effects on passive transfer of resistance to infection with Borrelia burgdorferi. AB - When irradiated hamsters are passively immunized with immune serum before challenge with Borrelia burgdorferi, they are completely protected from arthritis and infection. The complement dependency of this protection was addressed by treating hamsters with cobra venom factor. Depletion of complement abrogated the ability of immune serum obtained 1 and 10 weeks after infection to confer complete protection. By contrast, depletion of complement had no effect on the ability of 3-week immune serum to confer protection. These results suggest that complement-dependent, and possibly complement-independent, antibodies are important for preventing the induction of Lyme arthritis. PMID- 1894379 TI - Effects of temperature, amebic strain, and carbohydrates on Acanthamoeba adherence to corneal epithelium in vitro. AB - An in vitro coincubation assay was used to measure adhesion of radiolabeled Acanthamoeba trophozoites to corneal epithelium. Adhesion of amebae to corneal epithelium was higher at 25 degrees C than at 37 or 4 degrees C, did not consistently correlate with the reported pathogenicity of the strain of Acanthamoeba, and was inhibited by mannose and by methyl-alpha-D-mannopyranoside. PMID- 1894380 TI - Persistent cryptosporidiosis in horses with severe combined immunodeficiency. AB - Cryptosporidial infections were established in five young foals with severe combined immunodeficiency following oral administration of 10(8) Cryptosporidium parvum oocysts. All foals shed oocysts (average of 8 x 10(6) to 2 x 10(8)/g of feces) until death. Inflammation and C. parvum organisms were observed in the common bile duct, duodenum, jejunum, and ileum. Since foals with severe combined immunodeficiency lack functional T and B lymphocytes and are incapable of antigen specific immune responses, they are well suited for evaluating the pathogenesis and treatment of persistent cryptosporidiosis. PMID- 1894381 TI - Recombinant human tumor necrosis factor alpha promotes adherence of Staphylococcus aureus to cultured human endothelial cells. AB - Tumor necrosis factor (TNF), a potent inflammatory mediator secreted by monocytes during inflammation, was shown to significantly increase the adherence of Staphylococcus aureus to cultured human umbilical vein endothelial cells in vitro. The stimulatory effect of TNF was dose dependent and was bimodal with respect to time; bacterial adhesion peaked after 4 and 16 h of stimulation with recombinant human TNF-alpha. The ability of TNF-alpha to augment staphylococcal adherence to endothelial cells was contingent upon the presence of plasma factors. Thus, the complex interaction among cytokines (such as TNF), plasma factor(s), and the endothelium serves to modulate bacterial adherence to endothelial cells. PMID- 1894382 TI - Comparison of pertussis toxin (PT)-neutralizing activities and mouse-protective activities of anti-PT mouse monoclonal antibodies. AB - An assay of neutralizing activity against CHO cell-clustering activity, one of the most common assays for anti-pertussis toxin antibodies, did not correlate well with an assay of the protective activities of monoclonal antibodies. A better correlation between neutralization of leukocytosis-promoting or islet activating activity and mouse protection against aerosol challenge was seen. PMID- 1894384 TI - Hypnotic induction in dentistry--coping with the fear of losing control (autonomy): a brief communication. AB - A common cause of stress among dental patients is the patient's fear of losing control in face of the "helplessness provoking" dental situation. Although hypno relaxation and hypnosis serve as efficient tools to aid in the administration of dental treatment to such patients, some of them may view hypnosis as a further relinquishing of control to the hypnotist and thus resist hypnotic induction, despite their willingness to try to use hypnosis for therapeutic reasons. To avoid this resistance, a "self-control" induction method is suggested that enables the patient to remain in control throughout the process. This technique minimizes the threat of losing one's autonomy and thus enables treatment of these patients. PMID- 1894383 TI - Prior immunologic experience potentiates the subsequent antibody response when Salmonella strains are used as vaccine carriers. AB - Prior immunologic experience with homologous and heterologous serotype Salmonella strains potentiated the subsequent antibody response when the same strains were used as vaccine carriers of foreign antigens. This potentiation was positively correlated with the appearance of antibody directed against the lipopolysaccharide of the carrier strain. Both serum and mucosal antibody responses against the foreign antigen increased over time. Antibody responses in sera of animals primed with either the homologous or heterologous serotype strain were not statistically significantly different, while animals primed with the homologous serotype strain developed significantly better mucosal antibody responses against the foreign antigen. PMID- 1894385 TI - Antecedents of posttraumatic stress disorder: wasn't being raped enough? A brief communication. AB - Many rape victims, like those traumatized by war, accidents, and natural disasters, are able to recover from their ordeal with supportive, crisis-oriented treatment. For others, however, symptoms may persist and require more intensive treatment. Hypnosis allows a modulated re-experiencing and abreaction of the traumatic event that can help to provide the victim with a relieving sense of mastery, and it fosters a receptive context for reassurance and interpretation regarding the irrational or exaggerated thoughts and feelings involved. 2 case examples are presented in which earlier conflicts appeared to play a role in perpetuating the patients' symptoms. Detecting and addressing these antecedents resulted in complete alleviation of long-standing problems through relatively brief treatment using hypnosis. PMID- 1894386 TI - The effects of hypnosis and of imagery on bleeding time: a brief communication. AB - 2 studies are reported, one using hypnotized Ss selected on hypnotizability and one using Ss selected on imagery vividness, whose purpose is to examine whether non-patient Ss can control their bleeding in a laboratory setting. All Ss were cut on both arms with the "Surgicutt" device, an instrument that automatically makes a cut that will bleed from 2 to 10 minutes. Results suggest that Ss, who are instructed to reduce the bleeding time in one arm and to let the other arm bleed normally, are not able to control bleeding time. PMID- 1894387 TI - Hypnotizability as related to visually induced affective reactivity: a brief communication. AB - Numerous studies have explored the relationship between hypnotizability and individual differences in imaginative involvement and creativity. Most have assessed imaginative or affective involvement by involving Ss in a variety of imaging tasks. Unlike these earlier studies, however, the present study made no attempt to actively involve Ss in the film viewing task. Rather, individuals assessed as high, medium, or low in hypnotizability were exposed to either a violent film, a neutral film, or no film. Results provided tentative evidence to indicate that the level of negative affect reported was significantly greater for highly hypnotizable Ss. Results were discussed in terms of the limitations of the present study and implications for future studies. PMID- 1894388 TI - Hypnotherapy in the treatment of the chronic nocturnal use of a dental splint prescribed for bruxism. AB - A behavioral medicine case is described in which the patient was treated with a combined approach involving both hypnoanalytic and hypnobehavioral techniques. A 55-year-old man with bruxism was referred after 10 years of craniomandibular treatment because of his dependency on a dental splint prescribed for nocturnal use. A projective hypnoanalytic exploration helped to uncover and consequently resolve an earlier conflict that had been reactivated in the patient's work situation and which had become a constant source of mental and muscular tension. The hypnoanalytic exploration was followed by a cognitive-behavioral hypnotic intervention that was tape-recorded and prescribed for bedtime practice. Pre- and posttherapy psychological, physiological, and self-report measurements corroborated the patient's sense of well being that came with his newly found ability to sleep without the dental splint. The importance of considering multiple etiological factors in the treatment of such psychosomatic disorders as bruxism is discussed. PMID- 1894389 TI - Dissociation in hypnosis and multiple personality disorder. AB - The first part of this paper examines the concept of dissociation in the context of hypnosis. In particular, the neodissociative and social psychological models of hypnosis are compared. It is argued that the social psychological model, in describing hypnotic enactments as purposeful, does not adequately distinguish between behavior that is enacted "on purpose" and behavior that serves or achieves a purpose. 2 recent dissertations (Hughes, 1988; Miller, 1986) from the University of Waterloo are summarized, each of which supports the neodissociative view that hypnotic behavior can be purposeful (in the sense that the suggested state of affairs is achieved) and nonvolitional (in the sense that the suggested state of affairs is not achieved by high level executive initiative and ongoing effort). The second part of the paper employs a neodissociative view of hypnosis to help understand the current epidemic of multiple personality disorder (MPD). In particular, it is argued that many symptoms of MPD are implicitly suggested effects--particularly prone to occur in persons who have a lifelong tendency to use dissociative type defenses. The present author believes that this account is easier to sustain conceptually and empirically than the current view, which states that a secondary (tertiary, etc.) personality accounts for the striking phenomenological discontinuities experienced by MPD patients. PMID- 1894390 TI - Sports and the immune system. International Symposium of the German Federation of Sports Medicine. Paderborn, November 17-18, 1989. PMID- 1894391 TI - Sports and allergy. AB - Allergic and asthmatic individuals may have exercise-induced respiratory problems and sports may induce, in some cases, allergic problems. Exercise-induced asthma (EIA) differs from common asthma only in its causative factor. It is a typical asthmatic attack following physical exercise, lasting 5-10 min, most often in cold and dry weather. The prevalence in asthmatic children is high, in adolescents not yet firmly established. Cold air and/or hypertonic bronchial challenges during exercise are discussed as pathophysiological mechanisms. Nonpharmacological and drug treatment of EIA must preferentially be preventive. Exercise-induced anaphylaxis (urticaria, pruritus, edema) occurs mainly in children, triggered by exercise alone or by the combination of sensitizing food and exercise. Antihistamines before exercise are recommended. The use of sport equipment can induce contact dermatitis in rare cases. PMID- 1894392 TI - Psychological aspects of staleness and dependence on exercise. AB - This article discusses the psychological symptoms of overtraining and the relationship between staleness and exercise dependence. Staleness may be prevented by monitoring the mood state of the individual so that, if necessary, appropriate action may be taken to taper the volume of training and maximize performance. The criterion for exercise dependence is difficult to define and some suggestions are made on clarifying the diagnosis and future research in this area. PMID- 1894393 TI - The immune system: cells and molecules for the integration of self and non-self. AB - In a reductionist view, the immune system consists of 4 cell types, 3 diverse receptor systems and 10 to 15 soluble mediators including lymphokines and antibody molecules. Using these elements, the immune system generates 3 different effector mechanisms: Activated macrophages for the killing of intracellular microorganisms, cytotoxic T cells for the killing of virus-infected cells, and antibodies for the neutralization of soluble and cell-associated antigens of various types. While it is already very difficult to derive reliable results form reductionists experiments, such as studying immune responses in culture systems, it is infinitely more complicated to study the influence of physical exercise on the immune system. PMID- 1894394 TI - Influence of physical activity on the cellular immune system: mechanisms of action. AB - This review deals with the effect of acute physical exercise and training status on different components of the immune system. Predominantly studies in humans are mentioned. In relation to acute physical exercise (75% of VO2max, 1 hour) the leukocyte concentration increased; following exercise the neutrophils increased fourfold. The lymhphocyte concentration increased during and decreased following exercise. The percentage of CD3+ cells (pan T cells) declined during exercise, mainly due to a fall in the %CD4+ cells. The %CD16+ cells (NK cells) increased two-fold and returned to prevalue two hours after exercise. The %CD20+ cells (B cells) did not change in relation to exercise, whereas the %CD14+ cells (monocytes) increased two to threefold following exercise. The NK cell activity increased during but decreased following exercise. These increases were due to recruitment of NK cells with a high IL-2 response capacity, whereas the decreased NK activity post-exercise was due to downregulation by prostaglandins released by the elevated concentration of monocytes. During severe, moderate as well as light exercise, the NK cell activity increased, but the post-exercise suppression of the NK cell function was found only following severe exercise, and not after moderate or light exercise, furthermore, only following severe exercise, an increased monocyte concentration was demonstrated. The IL-2-stimulated lymphocyte proliferative response increased due to stimulation of CD16+ cells and did not reflect expression of IL-2 receptors. PMID- 1894395 TI - Interaction between hormones and the immune system. AB - After a short introduction into the general topic, the catecholamine-induced increase of leukocytes in which the granulocytes are predominant after short-term exercise is discussed. The reduction of lymphocytes is associated with work dependent cortisol increase after long-term exercise or 1 h after strenous work. The catecholamine-stimulated lymphocytes increase could be explained by the liberation of the cells from the endothelial vessel wall after catecholamine interaction with the beta-adrenoceptors and by mobilization from lymph nodes and spleen after beta-adrenergic stimulation. Catecholamines reduce the proliferation of lymphocytes and the degranulation of mast cells, preventing hypersensitivity reaction due to inhibited mediator liberation. The influence of cortisol and cytokines and vice versa is discussed. The hormonal changes after runs of different intensities and duration are demonstrated; they show an interaction with immunological regulation. The neuroimmune modulation after physical and psychological stress also has to be considered in immune regulation since under this condition the secretion of encephalins, endorphins, ACTH, and cortisol is increased. The significance of enhanced vasopressin secretion causing postural fainting by vagovasal reaction indicates also the effect of a neuropeptide which is related to immunological reactions. In the changes of lymphocyte subclasses, the homing effect of these cells should be regarded. Advices which can improve the immunologic behaviour, avoiding susceptibility to infections by well conducted training regimens and adequate periods of regeneration time, are necessary.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1894396 TI - Cell biological aspects of HIV-1 infection: effect of the anti-HIV-1 agent Avarol. AB - HTLV-I, II, HIV-1, 2 and other retroviruses possess genes for the transcriptional activators, tax and tat, the expression of which is closely related with the pathogenesis of leukemia and human immunodeficiency syndrome (AIDS) and induced by the virus infection. The effects of these activators on the expression of host cell genes, however, are still largely unknown. Recently the authors have discovered that infection with HIV or Mo-MuLV causes a specific acceleration of the synthesis of an UAG suppressor glutamine tRNA in the host cell; they could demonstrate that this phenomenon is based on transcriptional promotion of tRNA genes which is due to a new transcriptional activator synthesized as a function of viral infection and/or increased virus levels. The present paper discusses the significance of the suppressor tRNA and explains the role of the virus in the regulation of its expression. PMID- 1894397 TI - Overtraining increases the susceptibility to infection. AB - Recent research studies and other evidence suggest that although moderate exercise is good for the immune system, the demanding training programs of many top athletes may suppress the immune system and thereby increase susceptibility to infections. A number of top athletes have suffered from unusual infections normally associated with immune deficiency, and immune abnormalities have been demonstrated in resting samples from top athletes. Studies from several exercise laboratories have shown that after a single exhausting exercise session there is temporary immune depression, with marked changes in numbers and functional capacities of lymphocytes. These changes, which last for up to several hours, are seen in athletes and untrained individuals. In several studies in the United States, students who were very active in sports have been shown to be more susceptible to infections than their less active colleagues. Exercising hard during the incubation phase of an infection can increase the severity of the illness. This article examines the evidence, discusses possible mechanisms, and considers the implications. PMID- 1894398 TI - Psychosocial factors, exercise, and immunity: athletes, elderly persons, and AIDS patients. AB - Maximal bicycle ergometry exercise increases natural killer (NK) cell activity and numbers in both healthy old and young persons to equivalent degree but with greater variability in the old. Exercise-induced increase in NK activity, but not numbers, is blocked by the opioid antagonist naloxone. Lactating females do not show exercise-induced augmentation of NK cell activity. A predisposition to autoimmune disease, particularly rheumatoid arthritis, may exist among athletes, and disease may ensue when athleticism ceases. Long-term survivors with AIDS generally engage in physical fitness/exercise programs. PMID- 1894399 TI - Can endurance sports stimulate immune mechanisms against cancer and metastasis? AB - Proceeding from a brief historical contemplation of the problematic nature of "exercise and malignancy" a training investigation (running on a treadmill) with animals is presented. By means of the experimental tumor model fibrosarcoma L-1 of BALB/c mice differences in growth, size, and metastatic spreading have been proven depending upon the mode and more significantly on the intensity of training and upon the mode of application and inoculation of tumor cells. Accordingly the best cancer protective effect could be observed when the animals performed a pre- and a post-running training before and after inoculation. More over mechanisms of the acute phase response of human athletes are discussed in relation to possible prophylactic effects on the prevention of infections and on the development of cancer. PMID- 1894400 TI - Chronic urticaria. Evaluation of the role of physical, immunologic, and other contributory factors. PMID- 1894401 TI - Mycetoma. Current concepts in treatment. PMID- 1894402 TI - Porphyrias and porphyrins. PMID- 1894403 TI - Ectomesodermal dysplasia syndrome (focal dermal hypoplasia). PMID- 1894404 TI - A retrospective look at dermatologic education for primary care in United States medical schools. PMID- 1894405 TI - Studies on criteria of the European Academy of Dermatology and Venerology for the classification of cutaneous lupus erythematosus. I. Selection of clinical groups and study factors. AB - A group of 140 cases of various forms of lupus erythematosus (LE) were examined for 24 variables, including the 11 criteria of the American Rheumatism Association (ARA) for the classification of systemic lupus erythematosus (SLE), and 13 additional criteria suggested by the European Academy of Dermatology and Venerology (EADV) for studies of cutaneous LE with or without systemic involvement. The EADV study factors included skin histopathology and immunopathology, complement and IgG levels, and other laboratory tests, as well as selected clinical findings, most notably the papulosquamous and/or annular lesions that characterize subacute cutaneous LE (SCLE). The patients examined included 50 SLE, 35 SCLE, 30 discoid LE (DLE), 25 disseminated DLE (DDLE), and 17 polymorphous light eruption (PMLE) cases. Preliminary analyses of the data reveal the following: (1) The SCLE cases differed significantly from SLE, DLE, and DDLE in 10 of 11 ARA criteria (all but photosensitivity). (2) The frequencies of positive findings in SCLE also differed significantly for 11 of 13 EADV study factors. (3) While no significant differences appeared in the frequency of photosensitivity between the five study groups, photo-testing revealed significant increases in the frequency of persistence of the photo reactions for 10 days and their Koebnerization in the SCLE cases. (4) The presence of SS-A (Ro)/SS-B (La) antibodies had some predictive value for the appearance of systemic involvement in SCLE, as seen by the increased frequencies of five or more ARA criteria, although highly significant differences from SLE occurred in the absence of renal involvement and lower frequency of ANA and LE band test.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1894406 TI - Superficial granulomatous pyoderma. AB - Superficial granulomatous pyoderma, recently described as a variant of pyoderma gangrenosum, would be better termed pathergic granulomatous cutaneous ulceration as the seven previously described cases, as well as our own two cases, have significant dermal involvement histologically and heal with scarring. In contrast to pyoderma gangrenosum, lesions of superficial granulomatous pyoderma respond to less toxic anti-inflammatory agents. PMID- 1894407 TI - Antibasement membrane zone antibodies in localized pretibial pemphigoid. AB - To clarify the nosologic position of localized pretibial pemphigoid, Western immunoblotting analysis was carried out using the sodium dodecyl sulfate extracts of normal human epidermis. Sera from patients with localized pretibial pemphigoid and generalized bullous pemphigoid reacted with 220- to 240-kd polypeptide, which is a critical point for a definite diagnosis of bullous pemphigoid. This result suggests that localized pretibial pemphigoid belongs to the same nosologic position as bullous pemphigoid. PMID- 1894408 TI - Regional dermatoses in the African black. III. Pretibial lesions. PMID- 1894409 TI - Cutaneous malignancies mimicking herpes zoster. AB - Cutaneous metastases occur in 2.5% to 5% of patients with malignant disease. The relative frequency of the primary site roughly parallels the frequency of the various malignancies in each sex. We present two cases of cutaneous malignancy occurring in a dermatomal distribution and masquerading as herpes zoster. The differential diagnosis of zosteriform eruptions is reviewed and the possible pathogenesis of metastatic disease in this cutaneous distribution is discussed. Skin biopsy is recommended in these cases to determine the etiology of the eruption. PMID- 1894410 TI - Bibliography of secondary sources on the history of dermatology. I. Journal articles in English supplemented through 1990. PMID- 1894411 TI - Cutaneous T-cell lymphoma in association with leukocytoclastic vasculitis. PMID- 1894413 TI - Black widow spider poisoning as a possible cause of toxic epidermal necrolysis. PMID- 1894412 TI - Granuloma disciformis chronica et progressiva (Miescher) mimicking tuberculoid leprosy. PMID- 1894415 TI - Involvement of the uterine cervix in benign familial chronic pemphigus. PMID- 1894414 TI - AIDS and psoriasis. PMID- 1894416 TI - More specifics on the international traveling chair of dermatologic surgery. PMID- 1894417 TI - Traumatic plantar plaques of childhood. PMID- 1894418 TI - Granuloma annulare: a rare occipital lesion in a man. PMID- 1894419 TI - Unilateral nevoid acanthosis nigricans. PMID- 1894420 TI - Lichen striatus and atopy. PMID- 1894422 TI - Elevated blood pressure in obese children: influence of gender, age, weight and serum insulin levels. AB - Prepubescent and early pubescent obese children (n = 114, mean percent IBW = 165, mean age 7.3 years) were studied to determine the relationship of weight (WT), percent of ideal body weight (percent IBW), gender, and insulin (I) to systolic (SBP) and diastolic (DBP) blood pressure. Subjects were assessed for weight, height, percent IBW, systolic and diastolic blood pressure, and Tanner stage; subjects with Tanner stage greater than 3 were excluded. Multiple regression revealed that body weight accounted for the greatest variance in SBP (adj. R2 = 0.34, P less than 0.05), followed by the age. For DBP, weight also accounted for the greatest variance (adj. R2 = 0.16, P less than 0.05) followed by gender. A subgroup (n = 50) was evaluated for oral glucose tolerance. Subjects ingested 1.75 g glucose (GLU)/kg weight and had blood samples drawn at 0, 30, 60, 90, 120 and 180 min. Pearson correlations showed SBP correlated significantly to I at 0 (r = 0.44) and the total integrated area for insulin (r = 0.45); however, adjusting SBP for age by using z-score transformations negated all correlations between SBP and insulin. GLU at 0 and the total integrated area were not significantly correlated to SBP or DBP in absolute or age-adjusted terms. These data on prepubescent, nondiabetic, obese children suggest an association between insulin and elevations in SBP, but not DBP, that is largely due to a mutual association between age and weight. Also, insulin resistance as reflected in GLU response was not related to SBP or DBP. PMID- 1894421 TI - Relationships of obesity indices to serum insulin and lipoproteins in relatives of black patients with noninsulin-dependent diabetes mellitus (NIDDM). AB - We have examined the relationships between obesity indices and various metabolic parameters in seven obese (body mass index (BMI) mean +/- s.e.m. 42 +/- 2.5 kg/m2), ten nonobese (BMI 25.3 +/- 1.2 kg/m2) nondiabetic female relatives of black patients with NIDDM and eight healthy controls (BMI 24.5 +/- 1.1 kg/m2). Despite the greater BMI in the obese relatives, percent body fat was not different from that of the nonobese relatives (38 +/- 2 vs 34 +/- 3 percent). Both values were, however, significantly (P less than 0.05) greater than that of the healthy controls (25 +/- 3 percent). Mean waist-to-hip circumference ratio (WHR) was greatest in obese relatives (0.89 +/- 0.01), intermediate in nonobese relatives (0.83 +/- 0.01) and least in the healthy controls (0.77 +/- 0.04). Mean sum of skinfold thickness from biceps, triceps and subscapular (SS) region was also greatest in obese relatives, intermediate in nonobese relatives and least in controls. Centrality index was not, however, different among the groups. Mean fasting serum glucose levels were slightly higher but not significantly different in the relatives compared to controls (obese 82 +/- 3; nonobese 81 +/- 4; controls 75 +/- 3 mg/dl). Following oral glucose ingestion, serum glucose rose to significantly (P less than 0.05) greater levels at 30, 60 and 90 min in the relative subgroups vs controls. Mean fasting and post-prandial peak serum insulin concentrations were significantly (P less than 0.05-0.01) greater in both relative subgroups vs controls. While mean serum glucose profiles and glucose disappearance decay (KG) following intravenous glucose load were identical in the relatives and controls, serum insulin responses were significantly greater in the relatives. The mean basal and post-stimulation serum C-peptide concentrations were similar in all the three groups, irrespective of the stimulus; thus suggesting a reduced hepatic insulin extraction in the relatives. Fasting serum cholesterol, triglyceride, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) as well as FFA levels were not different between the relatives and controls despite the hyperinsulinemia in the former group. WHR correlated with basal insulin in the relatives (r = 0.416, P less than 0.05) and controls (r = 0.68, P less than 0.01) but not with stimulated insulin, lipids and lipoproteins in any of the groups. In contrast, both percent BFM and SS thickness correlated significantly (P less than 0.001) with post-glucose insulin concentrations in the relatives only.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1894423 TI - Comparison of the enteroinsular axis in two strains of obese rat, the fatty Zucker and the JCR:LA-corpulent. AB - The 'fatty' Zucker and more recently the JCR:LA-cp 'corpulent' have been studied extensively as genetic models of the hyperinsulinemia, insulin resistance and abnormal fat metabolism of obesity. It has been hypothesized that an abnormal enteroinsular axis leading to hypersecretion of the insulin releasing hormone gastric inhibitory polypeptide (GIP) could contribute to the hyperinsulinemia of obesity, although this has been controversial. The present study was undertaken to compare the enteroinsular axis in fatty Zucker and JCR:LA-cp rats. The in vivo GIP and insulin responses to an oral glucose challenge, as well as glucose tolerance, were compared in lean and obese phenotypes of both strains as well as the sensitivity of the perfused pancreas to the secretagogues glucose, arginine and GIP. In addition, the effect of perfusate glucose concentration on the beta cell response to GIP was assessed in both strains. Tissue samples from the pancreas were taken for immunocytochemical analysis of comparative size and composition of pancreatic islets. Our results indicate that corpulent rats are hyperGIPemic when compared to fatty Zuckers and that hyperinsulinemia (both in vivo and in vitro) is more severe in the JCR:LA-cp than in the fatty Zucker, as is the degree of insulin resistance (as evidenced by glucose intolerance). Islets of corpulent rats were found to be larger than those of fa/fa rats as well as having a larger area occupied by beta cells. It was concluded that GIP may contribute to fasting hyperinsulinemia in the Zucker rat (as a result of a defective glucose threshold for the insulinotropic action of GIP), whereas the hyperGIPemia of the JCR:LA-cp rat may contribute to the massive nutrient stimulated hyperinsulinemia observed in the male phenotype of this strain. PMID- 1894424 TI - Increased upper body and overall adiposity is associated with decreased sex hormone binding globulin in postmenopausal women. AB - An unfavorable body fat distribution is associated with many metabolic abnormalities including a high prevalence and incidence of noninsulin dependent diabetes mellitus and decreased high density lipoprotein cholesterol and increased triglyceride levels. One mechanism for the effect of body fat distribution on metabolic variables may be through sex hormones. We examined the relationship of body mass index (BMI), ratio of subscapular-to-triceps skinfold ratio (centrality index) and ratio of waist-to-hip ratio (WHR) to sex hormone binding globulin (SHBG) (an in vivo measure of androgenicity) in 101 postmenopausal Mexican-American and non-Hispanic white women from the San Antonio Heart Study, a population based study of diabetes and cardiovascular disease. SHBG was significantly correlated with BMI (r = -0.440, P less than 0.001), WHR (r = -0.255, P less than 0.01) and centrality index (r = -0.210, P less than 0.05). In a multiple linear regression analysis, SHBG remained significantly associated with BMI (P less than 0.001) and WHR (P less than 0.05) but not with age, ethnicity or centrality index. This work suggests that in postmenopausal women overall adiposity and an unfavorable body fat distribution are associated with increased androgenicity as measured by a lower SHBG concentration. Our finding may help to explain the association of body fat distribution with diabetes and cardiovascular risk factors in older women. PMID- 1894426 TI - Nutrient intake of obese children in a family-based behavioral weight control program. PMID- 1894427 TI - Echinococcus and Giardia: variation on a theme. PMID- 1894425 TI - Abnormalities of plasma lipoproteins in a new genetically obese rat with non insulin-dependent diabetes mellitus (Wistar fatty rat). AB - We investigated plasma lipoprotein profiles and the activities of tissue cholesterol regulating enzymes in Wistar fatty rats, an animal model for non insulin-dependent diabetes mellitus (NIDDM). Wistar fatty rats were made by transfer of the fa gene to the Wistar Kyoto rats by backcross-breeding. Wistar fatty and control non-diabetic littermates were given a laboratory chow or an atherogenic diet containing 1 percent (weight percent) cholesterol, 0.5 percent cholic acid, and 5 percent lard. Under the chow diet, plasma fasting glucose and immunoreactive insulin concentrations in Wistar fatty rats were 1.5- and 6-fold higher than controls, respectively. Plasma cholesterol was significantly increased in Wistar fatty rats compared with controls. Elevated plasma cholesterol levels in Wistar fatties was accounted for by the increases of cholesterol content in the d less than 1.006 g/ml lipoprotein and high-density lipoproteins. Under the atherogenic diet, plasma cholesterol levels in Wistar fatties were further increased by 129 percent compared with controls. The diet induced increase of cholesterol contents was shown in all lipoprotein classes for Wistar fatty rats. The activities of regulatory enzymes for cholesterol biosynthesis or absorption were measured in Wistar fatty rats. Both hepatic and intestinal 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase activities were significantly higher in Wistar fatty rats than those in controls (P less than 0.05 and P less than 0.01, respectively). ACAT activities in Wistar fatties were significantly increased in the intestine (P less than 0.05) and decreased in the liver in comparison with controls (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1894428 TI - Seasonal dynamics of Fasciola hepatica burdens in grazing Timahdit sheep in Morocco. AB - Seasonal transmission of Fasciola hepatica was observed in sentinel sheep and the dynamics of the snail intermediate host, Lymnaea truncatula, was followed over a 3-year study period in the Middle-Atlas mountains in Morocco. High fluke burdens were recorded in both lambs and ewes in the fall and winter, suggesting that transmission occurred in late spring. Fluke burdens ranged from one to 302 in ewes and from one to 345 in lambs. Infections with 200 or more flukes were always fatal. A unique feature of this study was the annual cyclical fluctuation of the fluke burdens. Burdens reached maximum levels during the winter and then declined to low numbers by late spring and summer. This suggested self-regulation which may be dependent on breed resistance or may be related to forage factors, including lack of forage (nutritional stress). Snail populations were cyclical and correlated with fluke transmission as observed in the sentinel sheep. The weather was observed to affect the snail populations which in turn limited fluke transmission. PMID- 1894429 TI - Specific antigen of Gnathostoma spinigerum for immunodiagnosis of human gnathostomiasis. AB - Sera from four patients with parasitologically confirmed gnathostomiasis, 15 patients with presumptive gnathostomiasis, 64 patients with various parasitic infections and 19 healthy adults were studied by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) and Western blot analysis for their reactivities against somatic extract of Gnathostoma spinigerum third-stage larvae (L3). It was found that the L3 extract was highly complex consisting of more than 20 antigenic components, a few of which gave reactions with sera from the healthy controls. Extensive cross-reactions of the parasite's antigen with sera from patients with other parasitic infections occurred. A specific antigen of G. spinigerum with a mol. wt of 24,000 (24k) was found to react with all parasitologically proven patients, five of the presumptive patients, one of the patients with other parasitic infections and none of the healthy individuals. This 24k component of G. spinigerum is a potential diagnostic antigen for use in the immunodiagnosis of human gnathostomiasis. PMID- 1894430 TI - Immunity to Heligmosomoides polygyrus induced by subcutaneous vaccination with post-infection larvae. AB - The objective of this study was to investigate, using the Heligmosomoides polygyrus (= Nematospiroides dubius)-mouse model, whether live post-infection trichostrongylid larvae recovered from the intestinal wall of donor animals and placed subcutaneously would serve as vaccine protecting against oral challenge by third-stage (infective) larvae (L3). Experiments were conducted to determine the effect of number and age of post-infective larvae as well as age and sex of host on vaccination. Vaccinated BALB/cByJ mice were challenged with 30 L3 and total adult worm burdens compared between vaccinated groups and sham-treated controls (greater than 90% infection rates). All mice subcutaneously vaccinated with either five or 10 larvae harbored significantly fewer challenge parasites in their intestines than did sham-treated controls (P less than 0.001). Both young and mature mice were significantly protected against challenge by the subcutaneous larval vaccine. Adult female mice had significantly (P less than 0.05) fewer parasites than adult male mice. The age of the larvae (indicated as the days between infection and harvesting of the larvae) was important in that day-4 or day-6 larvae (L4) were significantly more protective (P less than 0.001) than day-2 (L3) or day-8 larvae (L5-preadult). Reduction in worm burden for young vaccinated animals ranged from 31 to 39% (P less than 0.001) and for mature animals from 88 to 100% (P less than 0.001). Passive transfer to serum resulted in the reduction of worm burdens by 26-40% (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1894431 TI - Conflicting phylogenetic hypotheses for the parasitic platyhelminths tested by partial sequencing of 18S ribosomal RNA. AB - Partial sequencing of the 18S ribosomal RNA in nine parasitic and one free-living species of platyhelminth was used to test hypotheses on the phylogenetic relationships among the major groups. The eucestodes, amphilinideans, gyrocotylideans and monopisthocotylideans appeared as a monophyletic assemblage in a cladistic analysis of the data, with a very close association between the gyrocotylideans and monopisthocotylideans. The polyopisthocotylidean monogeneans were paraphyletic to the monopisthocotylideans. The digeneans appeared to be a sister group to the monogeneans and eucestodes, while the temnocephalidean was closely related to the free-living polyclad. PMID- 1894432 TI - Protozoan and helminth parasites of humans in mainland China. AB - To date, 30 species of protozoa, 12 species of cestodes, 26 species of trematodes, 23 species of nematodes, two species of gordius and one acanthocephalan species hae been reported as parasites of man in mainland China. PMID- 1894433 TI - Aberrant energy-linked reactions in mitochondria isolated from the livers of sheep infected with the liver fluke Fasciola hepatica. AB - Respiration by mitochondria isolated from the livers of sheep following infection up to 15 weeks with F. hepatica was measured with the respiratory substrates pyruvate (plus malate) and succinate in the absence and presence of ADP; the rates were compared with those obtained by mitochondria isolated from livers of uninfected sheep. It was found that respiration supported by both substrates in mitochondria isolated from the left lobe but not the middle lobe of 4-week infected sheep exhibited abnormalities such that the acceptor control ratios were only marginally above one. Some, but not total, recovery was seen in the later stages of infection. The aberrant respiratory behaviour is similar to that observed with infected rats. PMID- 1894434 TI - Sucker-like structures in two strains of Acanthamoeba: scanning electron microscopy study. AB - Amebostomes are labile sucker-like structures repeatedly observed and described in Naegleria by different authors. Studying the phagocytic action of some Acanthamoeba species on Vero cells, the formation of similar structures to the Naegleria amebostomes was observed, apparently related to the phagocytic activity on cells. PMID- 1894435 TI - Schistosoma japonicum: changes in lipase activity in adults maintained in vitro. AB - Schistosoma japonicum (Chinese strain) adult worm pairs (10-12 weeks old) were fixed in 4 degrees C absolute acetone or neutral buffered formalin either immediately after recovery from mice, or following incubation for 0.5 or 1.0 h. Males and females were incubated individually in Earle's balanced salt solution at 37 degrees C. Lipase activity was determined in frozen sections by Gomori's method using Tween 80 as substrate. In unincubated males, lipase activity was localized only in the parenchyma; in females it was present in the vitellaria and parenchyma subjacent to the tegument. After 0.5 h incubation, males showed less lipase activity in the parenchyma than unincubated males, and females showed increased activity in the parenchyma subjacent to the tegument, but not in the vitellaria. Following 1.0 h incubation, males showed less lipase activity than previously, and females showed a marked increase in activity, particularly in the parenchyma subjacent to the tegument. PMID- 1894436 TI - Entamoeba histolytica: a simplified method to quantify its cytotoxicity. AB - A simplified and reliable method to quantify Entamoeba histolytica cytotoxicity was standardized. Mice spleen leucocytes were utilized as target cells. Interaction time was reduced to 1 h by pelleting interacting cells. To assess target-cell killing by amoebae, a nigrosine exclusion test was employed. Fixation with glutaraldehyde stabilized the percentage of stained target cells. Similar results were obtained when cytotoxicity of the E. histolytica HM1 strain was tested by the traditional and proposed methods. The new method allowed quantification of the contribution of cytolysis and cytophagocytosis to amoebic cytotoxicity. It was also demonstrated that uncloned E. histolytica HM1 strain is a heterogeneous population with respect to cytotoxicity expression. PMID- 1894437 TI - Studies on alanine aminotransferase in nematodes. AB - L-alanine aminotransferase was demonstrated in a range of gastrointestinal, free living and entomophagous nematodes. As in mammals, nematode L-alanine aminotransferase was found to exist in the form of mitochondrial and cytosolic isoenzymes. Whilst the majority of nematode enzymes exhibited a greater overall capacity for L-alanine synthesis than for L-alanine catabolism in vitro, the opposite was true for rat liver L-alanine aminotransferase. In contrast with rat liver, certain gastrointestinal nematodes were apparently able to transaminate D alanine at low rates. H. contortus cytosolic L-alanine aminotransferase differed significantly from the mammalian enzyme with respect to both thermal stability and response to potential protective reagents. PMID- 1894438 TI - Hepatic coccidiosis in the goat. AB - Coccidial oocysts were seen in the bile from five goats infected with coccidia either naturally or artificially. The oocysts measured on average 21.3 by 18.3 microns and resembled those of Eimeria ninakohlyakimovae. Livers and gall bladders of infected animals showed various degrees of histopathological changes. In the worst case, bile had a thick consistency and contained blood and necrotic debris. Apart from those in the bile, oocysts were seen in liver smears and in the centrilobular vein in two histological sections. Forms resembling meronts and measuring on average 200 by 147 microns were seen in sections of bile duct. PMID- 1894439 TI - In vivo cultivation of Echinococcus multilocularis protoscoleces in micropore chambers. AB - Micropore chambers containing unevaginated protoscoleces of E. multilocularis were implanted into the peritoneal cavity of AKR mice. Transformation from protoscoleces to fertile multivesicular cysts was obtained after 210 days. Ultrastructural observations of these morphological transformations indicate that a phase of histogenesis follows a phase of dedifferentiation. This morphogenetic process raises the question of the origin of new cell populations. The results reveal the potential role of protoscoleces in secondary echinococcosis and the value of this experimental model for further studies on the larval development. PMID- 1894440 TI - Effect of tertiary amine on the carbodiimide-mediated peptide synthesis. AB - The effect of tertiary amine (DIEA) on reaction rate and product purity of a carbodiimide/HOBt-mediated peptide synthesis was studied. It was found that very rapid activation can be achieved using carbodiimide/HOBt in non-polar solvents, such as DCM. Although the HOBt is poorly soluble in DCM, the activation proceeds within 2 min, probably forming the HOBt-ester. By such a preactivation followed by a coupling in the presence of DIEA the rate of coupling is comparable with other rapid methods using BOP or TBTU, and no racemization was found in a model coupling (less than 0.1%). For comparison, syntheses of neurotensin by means of different coupling reagents (BOP, TBTU, OPfp-esters) and the DIEA-catalyzed coupling after carbodiimide/HOBt-activation under comparable conditions have shown that these procedures are of the same value in view of coupling efficiency and product purity. PMID- 1894442 TI - Synthesis and properties of chemotactic peptide analogs. I. Crystal structure and molecular conformation of HCO-Met-leu-Ain-OMe. AB - HCO-Met-Leu-Ain-OMe (2), an analog of the chemotactic peptide HCO-Met-Leu-Phe-OH, containing the conformationally blocked residue of the 2-aminoindane-2-carboxylic acid (Ain) has been synthesized and its crystal and molecular conformation has been determined. Crystals of 2 are monoclinic, space group P2(1), with a = 15.059(7), b = 18.548(7), c = 9.600(4) A; beta = 85.04(3) degrees. The structure has been solved by direct methods and refined to R = 0.069 for 2813 independent reflections with I greater than 2.5 sigma (I). Two independent molecules A and B have been found in the asymmetric unit of the crystal of 2. Their conformation can be described as extended at the Met and Leu residues, but folded at the C terminal Ain residue. The helical folding is left- and right-handed in the A and B molecule, respectively. The crystal packing is characterized by ribbons of intermolecular hydrogen bonded molecules extended along the c direction. The constrained analog 2 is highly active in the superoxide production, thus indicating that a stabilization of a helical folding at the C-terminal region of chemotactic tripeptides maintains the activity. The orientation of the aromatic ring, with respect to its adjacent backbone atoms, does not seem critical for the activity. PMID- 1894441 TI - Spectroscopic analysis of [Trp3]-beta-casomorphin analogs. Comparative structure conformation-activity studies. AB - A series of [3-tryptophan]-beta-casomorphin-5([Trp3]-beta-CM-5) analogs were investigated by circular dichroism (CD) and fluorescence spectroscopy to explore their structure-conformation properties in solution. In addition, the comparative opioid activities of these compounds were evaluated using the in vitro guinea pig ileum (GPI) and mouse vas deferens (MVD) assays. Specifically, the pentapeptide sequence of [Trp3]-beta-CM-5, H-Tyr-Pro-Trp-Pro-Gly-OH (I) was modified at Pro-2 and Pro-4 by D-Pro substitutions to provide two diastereometric analogs, [Trp3-D Pro-4]-beta-CM-5 (II) and [D-Pro2,4,Trp3]-beta-CM-5 (III). In the GPI and MVD assays, beta-CM-5 effected IC50 values of 1.3 microM and 8.9 microM, respectively, which confirmed its known mu/delta-selectivity on these two peripheral opioid receptor subtypes. The potencies of compounds I, II, and III were 0.2, 2.0, and less than 0.005 relative to beta-CM-5 on the GPI assay. Compounds I and II exhibited pronounced mu/delta-selectivities (greater than 18.9 and 12.4-fold respectively), whereas compound III was essentially inactive in both the GPI and MVD assays. CD studies of beta-CM-5 and its [Trp3]-beta-CM-5 analogs showed striking differences in their near-UV and far-UV spectra in aqueous or organic solvents. In the far UV CD spectra, weak (20%) alpha-helicity (maximum at 193 nm and minima at 208 and 222 nm) for beta-CM-5 was obtained in trifluoroethanol (TFE); however, none of the [Trp3]-beta-CM-5 analogs showed such CD bands. Of potential relevance to gamma-turn or C7 secondary structure was the observation of a strong negative band at 245 nm for compounds II and III which was not solvent-dependent in H2O or TFE, whereas compound I showed this CD band exclusively in TFE. In the near-UV CD at 275 nm (Trp electronic transition), the relative order of intensities of this band were determined for the [Trp3]-beta-CM 5 compounds to be II greater than I greater than III, which was identical to their relative biological potencies in both the GPI and MVD assays. Fluorescence energy transfer (FET) experiments of compounds I-III provided the intramolecular distances (r) between their Tyr (donor) to Trp (acceptor) side-chains, by the Forster method, and were as follows: [Trp3]-beta-CM-5, r = 10.6 A; [Trp3, D-Pro4] beta-CM-5, r = 9.6 A; and [D-Pro2,4,Trp3]-beta-CM-5, r = 11.0 A.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1894443 TI - Contact area of bovine somatotropin dimer: involvement of tyrosine 142. AB - The presence of tyrosine residues in the contact area between protomers of bovine somatotropin dimers (Fernandez & Delfino, Biochem. J. 209, 107-115, 1983) was investigated taking advantage of the impaired self-associating ability of molecules iodinated at such residues. Reaction of bovine somatotropin dissolved in 8 M urea with the NaI-Chloramine T couple (2.1 x 10(-4) M) rendered a preparation with 3.1 iodine atoms per molecule which, by stepwise elimination of the denaturant and gel filtration through Sephadex G-100, originated two distinguishable populations: one able (iododerivatives I), the other unable (iododerivatives II) to self-associate. After frontal analysis, iododerivatives II were found to be unable to interact even with native molecules. Identification of the reacting tyrosine residues indicated that iodination of tyrosine 142 was responsible for the loss of the ability to form dimers in iododerivatives II. Iodohormones retained the ability to bind to somatogenic mouse hepatocyte receptors--the relative potency for iododerivatives I and II being 0.60 (0.34 1.03) and 0.71 (0.41-1.22) respectively. PMID- 1894444 TI - Synthesis, conformational studies, and molecular dynamics calculations of two cyclic tetrapeptides with 17- and 18-membered rings. AB - Two cyclic tetrapeptides [Boc-cyclo(-Xxx-Pro-Asn-Lys-)OMe (Xxx = Asp or Glu)] were synthesized and investigated by NMR spectroscopy. They were designed in order to mimic the salt bridge found in physalaemin. Isomers of the urethane bond were observed in DMSO solution. The ROESY spectrum allowed the assignment of many signals of the minor isomer of both compounds. Conformational studies based on the temperature gradients of the NH chemical shifts, coupling constants, and ROEs revealed a similar conformation for the Asp analogue as proposed for physalaemin. A beta I turn with Pro and Asn in the corner positions was found for the major isomer. No hydrogen bonds were detected for the major isomer of the cyclic Glu analogue. Molecular dynamics calculations, using the NMR based initial structures, yielded sets of conformations in agreement with the experimental data. It is concluded that the salt bridge in physalaemin is best approximated by a lactam formed from the original amino acids. PMID- 1894445 TI - Synthesis and conformational analysis of L-aspartylproline and L-aspartyl-2,3 methanoproline propyl esters. PMID- 1894446 TI - Determination of the structure of [Nle7]-endothelin by 1H NMR. AB - [Nle7]-endothelin was synthesized and studied by 1H NMR and distance geometry calculations. The NMR study was performed first in DMSO-d6 and then in 50% acetonitrile/water since this peptide aggregates in pure water. In both cases, all spin systems were identified and assigned with the aid of two-dimensional spectroscopy (2D): COSY (for scalar couplings) and NOESY (for dipolar couplings). On the basis of the acetonitrile/water NMR parameters, and using the DISGEO program, a three-dimensional structure of [Nle7]-endothelin is proposed and discussed. PMID- 1894447 TI - Modification of a zinc proteinase from Bacillus mesentericus strain 76 by diethylpyrocarbonate. AB - Diethylpyrocarbonate (DEPC) inactivated the neutral zinc proteinase from Bacillus mesentericus strain 76/Bacillus subtilis (MCP 76) by ethoxycarbonylation completely. Exposure of the enzyme to DEPC together with the competitive inhibitor Z-L-phenylalanine prevented the loss of activity toward both peptide and protein substrates. Treatment with hydroxylamine restored the catalytic properties of the modified MCP 76 to that of the native enzyme. After chymotryptic digestion of ethoxycarbonylated MCP 76 in the presence and absence of Z-L-phenylalanine a single histidyl residue essential for the enzyme activity was isolated and identified as histidine 231. PMID- 1894448 TI - Solid phase synthesis of a fully active analogue of cholecystokinin using the acid-stable Boc-Phe (p-CH2) SO3H as a substitute for Boc-Tyr(SO3H) in CCK8. AB - Substitution of the -OSO3H group in the sulfated-tyrosine by the non-hydrolyzable CH2SO3H group was the first described modification of the sulfate ester that does not affect CCK8 activity. In addition to its capacity to mimic the sulfated tyrosine residue, the amino acid Phe(p-CH2SO3Na) was shown to be stable in acidic media, including HF containing mixtures. The synthesis of Boc-Phe(p-CH2SO3Na)-OH in racemic and resolved forms and its introduction into the sequence of CCK8 by solid phase using standard Boc/benzyl synthesis conditions and BOP as coupling reagent is now reported. The two CCK8 analogues containing the L- or the D-Phe(p CH2SO3Na) residue, obtained in satisfactory yields, were separated by HPLC and the stereochemistry of Phe(p-CH2SO3Na) residue in each peptide was established by NMR spectroscopy and confirmed by a separate solid phase synthesis in which the pure L isomer was used. Both CCK8 analogues displayed high affinities for peripheral and central receptors (KI approximately 1 nM) and proved to be full agonists in the stimulation of pancreatic amylase secretion. The "stabilized-CCK8 peptide", easily prepared by solid phase, could replace the native peptide in biochemical and pharmacological studies. Moreover the modified amino acid Phe (p CH2SO3Na) could also be used in solid phase synthesis to prepare a wide variety of CCK analogues and more generally, peptides analogues containing the acid labile O-sulfated tyrosine. PMID- 1894449 TI - Use of Mpc-amino acids in solid phase peptide synthesis leads to improved coupling efficiencies. AB - The Mpc-group has a somewhat better stability than the Fmoc-group, resists catalytic hydrogenolysis, is highly stable in acidic media and its elimination product does not polymerize spontaneously. In a direct comparison of coupling efficiencies obtained in solid phase peptide syntheses using Mpc- or Fmoc-amino acids it is shown that the use of Mpc-amino acids leads to better coupling efficiencies and, consequently, a more homogeneous peptide. An improved synthesis of Mpc-ONSu and of Mpc-amino acid derivatives is presented. PMID- 1894450 TI - Diastereoselective hydrolysis of peptide esters by alkaline protease. Preparation of racemization-free peptides. AB - A new and practical enzymatic procedure for preparative diastereoselective hydrolysis of peptide esters using the alkaline protease alcalase as a catalyst was developed. This procedure has been successfully applied to the resolution of peptide diastereomers and synthesis of racemization free peptides. PMID- 1894451 TI - Psychiatrists' compliance with nonpsychiatric consultations: does compliance affect concordance? AB - Utilizing a systematic methodology (The Consultation-Liaison Outcome Evaluation System), the compliance of nonpsychiatric consultations within a general hospital psychiatric unit staffed by private practitioners was assessed. Thirty-one percent of the patients received such consultations and these patients had a longer length of stay than those without a consultation. Psychiatrists were generally compliant with both medication and diagnostic recommendations; but in only half the discharge summaries was the consultant's primary medical diagnosis fully reflected. The implications of these data are discussed. PMID- 1894452 TI - Correlations of cardiac function and SCL-90R in heart transplantation candidates. AB - Measurements of cardiac function and Symptom Checklist-90R (SCL-90R) data were retrospectively analyzed in two independent groups of cardiac transplant candidates in an effort to identify organic correlates of depressive syndromes. In the first study, no significant inverse correlations were found between depression measures and cardiac index as had been predicted. However, elevated right atrial pressure was associated with increased scores of the SCL-90R depression subscale (DEP) and global symptom index (GSI). A significant positive correlation was also found between the phobia subscale and cardiac index. In a second sample, again, cardiac index did not correlate inversely with DEP or GSI. The phobia-cardiac index correlation was replicated but the right atrial pressure correlations were not. Combining both groups, there were significant correlations between six SCL-90R subscales (including DEP and GSI) and cardiac index. All were positive correlations, refuting the initial hypothesis and suggesting patients with the best cardiac function reported the worst psychological distress and that patients with the worst cardiac function reported the least psychological distress. Possible explanations for these findings are discussed. PMID- 1894453 TI - The neuropsychiatry of Wilson's disease: a review. AB - Psychiatric symptoms are frequently encountered in Wilson's disease (WD). The recent resurgence of interest in neuropsychiatry has led to a more detailed consideration of the psychopathology associated with WD. As suggested by Wilson, disorders of affect, behavior and personality are the most common features. Contrary to Wilson's view, recent evidence suggests that such symptoms have an organic basis. Cognitive impairments tend to be mild and improve with treatment. There is a lack of recent evidence for an association between WD and organic delusional disorders. PMID- 1894454 TI - Psychological morbidity associated with local recurrence of breast cancer. AB - Twenty-two individuals who had suffered from local recurrence of breast cancer were interviewed to determine psychosocial morbidity. Psychometric assessment using the Hamilton Anxiety Scale, the Eysenck Personality Questionnaire and the Montgomery Asberg Depression Rating Scale was conducted prior to clinical evaluation including a structured interview, the Composite International Diagnostic Interview. Lifetime and current psychiatric diagnoses were established. Ten (45%) of the recurrence group had current psychiatric illness (anxiety and depression) at the time of local recurrence, a similar prevalence to that described by others at mastectomy. Previous psychiatric illness and trait neuroticism are predictive of vulnerability to psychiatric morbidity at local recurrence. These results suggest that a significant proportion of patients with local recurrence suffer from major depressive illness. PMID- 1894455 TI - Tricyclic drugs in pregnancy and lactation: a preliminary report. AB - The management of severe depression during pregnancy and lactation is a serious concern to both physicians and parents, since the use of tricyclic antidepressant drugs (TCAs) has not been proven to be safe. This is a preliminary report of our ongoing studies of four groups of women treated with tricyclic antidepressants before and during pregnancy and/or lactation. The four groups are women who: became pregnant while on TCAs (n = 9); were prescribed TCAs during pregnancy (n = 9); were prescribed TCAs during lactation (n = 20); or were clinically depressed during lactation, but who refused TCAs (n = 5). Our results to date on the very small number of subjects indicate that there have been no fetal malformations, no greater frequency of complications during labor and delivery than in the normal population, only short-term withdrawal symptoms in the neonate, and no adverse effects on the breast-fed infants of mothers on TCAs. However, all of the lactating mothers who refused TCAs had exacerbation of symptoms; two required treatment in hospital, and all five ultimately had to discontinue nursing and commence treatment with TCAs. PMID- 1894456 TI - The use of physical restraint in patients with cerebral contusion. AB - Behavioral problems resulting in the use of physical restraint is a clinical problem seen in the acute phase of recovery from cerebral contusion. However, little is known about the frequency of physical restraint, factors that might predispose to its use, the pattern of adjunctive psychotropic drugs used or the outcome for patients needing this form of management. In order to examine these issues, a retrospective study of all patients (N = 34) admitted with cerebral contusion to a neurosurgical service over a one-year period was undertaken. Physical restraint was used in twelve patients (35%) for an average length of 4.3 days. The use of physical restraint was associated with presumptive evidence of alcohol abuse or dependence but not with level of consciousness on admission. Restrained patients were frequently prescribed psychotropic drugs during hospitalization. Patients requiring physical restraint stayed in hospital nearly twice as long as those not needing restraint. Close attention to the identification and treatment of alcohol problems and their complications in this population may reduce the need for physical restraint and shorten length of hospital stay. PMID- 1894457 TI - Drug interaction between rifampin and nortriptyline: a case report. AB - This case illustrates a pharmacokinetic interaction between the tricyclic antidepressant, nortriptyline, and the antituberculosis drug, rifampin. Higher than expected doses of nortriptyline were required to obtain a therapeutic drug level while the patient was receiving rifampin. Following the discontinuation of rifampin, the patient became drowsy and the serum nortriptyline levels rose precipitously into the toxic range. The authors suggest that patients receiving rifampin and nortriptyline, (or other psychotropic drugs) be monitored closely and that similar drug interactions be anticipated. PMID- 1894458 TI - Sexual dysfunction, social maladjustment, and psychiatric disorders in women seeking treatment in a premenstrual syndrome clinic. AB - The NIMH Diagnostic Interview Schedule (n = 43), and the Hopkins Symptom Checklist and Weissman Social Adjustment Scale (n = 35) was administered to assess the prevalence of psychiatric disorders and psychosocial maladjustment present in women seeking treatment in a multidisciplinary Premenstrual Syndrome Clinic. We found a 67 percent lifetime prevalence of DIS/DSM-III psychiatric disorders: 50 percent Major Affective Disorder (primarily Depression), 53 percent Anxiety Disorder (primarily Phobias or Generalized Anxiety Disorder), and 40 percent Psychosexual Dysfunction (notably Inhibited Sexual Desire or Excitement). Our group had significantly greater Major Depression, Dysthymia, and any one psychiatric disorder compared with female general population samples. Two-thirds of women with premenstrual symptoms had true Premenstrual Syndrome. In our sample, social maladjustment as well as psychiatric symptomatology was significantly greater than in normals and closer to that in psychiatric out patient norms, and was independent of cycle phase. Presence or absence of PMS, social maladjustment and sexual dysfunction was each not significantly different in women with or without psychiatric disorder. PMID- 1894459 TI - Sources and consequences of satisfaction and dissatisfaction in nursing: findings from a national sample. AB - The implications for the current nursing shortage of the job satisfaction and dissatisfaction described by 252 members of the American Nursing Association are discussed. Comparison of sources of dissatisfaction by the frequency with which they were mentioned, the strength of emotion with which they were expressed and their potential to provoke defection from nursing, indicate inadequate working conditions and counter-productive attitudes within employing organizations to be the most serious sources of dissatisfaction. Dissatisfaction with remuneration and benefits rank second to structural problems, by each measure. The relative importance of problems with gender and family roles, colleagues, education, and professional associations, and of respect, recognition, and autonomy issues are also discussed. PMID- 1894460 TI - Stress and well-being in nurses: a comparison of the public and private sectors. AB - Nurses in the public and private sectors were compared with regard to occupational stress and its sources and self-reported health and well-being. While both groups reported similar high levels of stress experience, most noticeably arising from high work loads and the experience of death and dying, group differences did emerge from an examination of the sources of stress. Whereas N.H.S. nurses were more troubled by high work loads, private sector nurses reported uncertainty over treatment as a more frequent source of stress than did their N.H.S. counterparts. Levels of self-reported mental and physical health symptomatology did not differ between groups. Nevertheless, overall nursing stress scores and symptomatology were significantly correlated, and workload was the best independent predictor of health and well-being status. PMID- 1894461 TI - Teaching and support: nursing input in the postpartum period. AB - The findings from two studies, surveys of hospitals and community health units in Alberta, Canada, to determine the policies, procedures and content related to postpartum teaching are presented in this paper. While content covered was extensive the limited time available for teaching suggested that material would have to be presented at a superficial level, with little time for reinforcement. The average time for a home visit by the nurse was 7-12 days post-discharge and in some instances staff shortages precluded a second visit. The most frequent reason for follow-up visits in the community was problems with newborn feeding. Volunteer services in the community, such as the La Leche League, were frequently not recommended to mothers by hospital nurses, so breastfeeding mothers were left without support at a critical time. While the study did not support the mother's contention in an earlier study that they did not receive information, the lack of opportunity for expansion and reinforcement of provided information would mitigate against adequate maternal education. PMID- 1894462 TI - The impact of daily exercise on the mobility, balance and urine control of cognitively impaired nursing home residents. AB - The purpose of this intervention study was to examine the impact of a daily exercise regimen on the mobility, balance, and urine control of a sample of cognitively impaired elderly nursing home residents. A quasi-experimental pretest posttest design was used with 15 elderly, cognitively impaired, incontinent nursing home residents. Data were collected regarding walking distance, speed of walking, balance ability, ability to rise from a chair unassisted, ability to walk unassisted, and incidence of urinary incontinence before and after a month of daily assisted walking. Subjects were able to walk significantly greater distances before tiring after the exercise regimen. In addition, the incidence of urinary incontinence was significantly decreased. PMID- 1894463 TI - Plate waste producing situations on nursing wards. AB - This study examines the existence of a positive correlation of interferences during mealtime and the amount of plate waste. Textbooks prescribe a quiet and relaxed atmosphere. With an exploratory research design, data about the patient, his environment and plate waste were collected on a medical unit of an academic teaching hospital. Mealtime environmental conditions by no means met prescribed demands. The amount of plate waste correlated with movements made by laboratory and housekeeping personnel, visitors and physicians. Loss of appetite as well as related environmental factors are further discussed and elaborated. PMID- 1894464 TI - The development of a classification system for nurses' work methods. AB - This study describes the development of a classification system for the clarification, understanding and measurement of nurses' work methods. The theoretical basis of the classification system is described. The system offered distinguishes between three common work methods: primary, team and task nursing; the strength of opportunity for nurse-patient interaction in each method being determined as either 'strong', 'moderate' or 'weak', according to how effectively they are practised. Preliminary testing of the system on 32 wards in 13 hospitals is described. It is concluded that further testing and possible refinement is required for validation of the system. PMID- 1894465 TI - Working with families caring for a relative with schizophrenia: the evolving role of the community psychiatric nurse. AB - This paper describes the effect on the role and function of the community psychiatric nurse (CPN) after training to deliver psychosocial intervention to families caring for a relative with schizophrenia living at home. The study was undertaken as part of a larger investigation, commissioned by the Department of Health, which is examining outcome in families after CPNs have received training in psychosocial intervention strategies. In the last decade four major controlled studies have shown that relapse in schizophrenia can be improved if families receive; detailed assessments of individual need, health education about schizophrenia, and family stress management programmes, often defined as "psychosocial intervention". Whilst these research programmes have been underway, CPN services have been developing closer links with Primary Health Care and individual CPN's work with clients with severe and long-term mental illness has, as a consequence, been reducing. This trend has been rightly criticized, as has the tendency for CPN work to focus on the individual rather than the family with whom the client often lives. Informal carers willingly accept the burden of care for their relatives but their own needs are all too often neglected. The pilot phase of the outcome study demonstrated that after CPNs had received experimental training in psychosocial intervention, families reported a number of positive benefits when followed up for 12 months. First, for the clients there were improvements in the symptoms of their illness and in their social functioning. Second, carers' satisfaction with the service received showed a marked improvement as did their estimates of minor psychiatric morbidity. These changes in outcome entailed a cost. Experimental CPNs reported that undertaking family intervention was more time-consuming than "traditional" CPN care of the client with schizophrenia. Further, the data reveal that the training led to CPNs extending their role in a variety of other ways even though they received only a modicum of support from colleagues within their own health authorities. This preliminary paper concludes that although family work undertaken by CPNs should be seen as an important priority, problems may arise as services attempt to juggle finite resources with ever growing demands. Guidance on the future role of the CPN from the Department of Health is essential and would greatly enable planners and managers alike to rank order service priorities. PMID- 1894466 TI - Detection of platelet mitochondrial DNA deletions in Kearns-Sayre syndrome. AB - To establish a noninvasive genetic diagnosing method for Kearns-Sayre syndrome, the authors used the polymerase chain reaction (PCR) technique for detecting mitochondrial DNA (mtDNA) deletions in the platelets and directly sequenced the crossover regions of the deleted mtDNA using the fluorescence-based automated sequencing system. The mtDNA deletions were identified in the platelets of three of four patients. The sizes and locations of deletions were determined by the nesting primer PCR method, in which the primary PCR products derived from deleted mtDNAs undergo reamplification using a series of nesting primers. With the fluorescence-based sequencing of templates amplified by the asymmetric PCR method, deleted mtDNA was sequenced directly without cloning. In patient 1, guanine (G) was found at the boundaries of a deleted segment spanning 8400 base pairs (bp) between the CO1 and ND6 genes. In patient 2, a 9-bp directly repeated sequence of 5'-ACCTCCCTC-3' (where A = adenine, C = cytosine, and T = thymine) was found at the boundaries of a deleted segment spanning 7221 bp between the CO1 and ND5 genes. In patient 3, an 8-bp sequence of 5'-TCGCTGTC-3' was found at the boundaries of a deleted segment spanning 4664 bp between the ATPase6 and ND5 genes. Deletions were not detected in the mtDNA of patient 4 or in that of the mothers of the patients. Previously, the genetic diagnosis of this syndrome required muscle biopsy specimens and the use of Southern blot analysis. However, this method requires neither muscle biopsy nor isotopes and is more rapid than the Southern blot method.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1894467 TI - Rod densitometry in the aging human eye. AB - Retinal densitometry is a noninvasive physiologic technique used to examine the visual pigments in living human eyes. To assess possible age-related disturbances of rod photopigment kinetics, retinal densitometry was done in 44 eyes of 44 healthy subjects (age range, 12-78 yr). With progressing age, a significant but small increase in photopigment density difference (bleached versus dark adapted eye) and an increase in the time constant of rhodopsin regeneration was found. The increased density difference in rods was consistent with morphologic findings of increased rod outer segment diameter and disc content in older subjects. To explain this change in terms of the decreased specular reflections at the level of the inner limiting membrane was inadequate because age effects were independent of wavelength in the region of 450-550 nm. To control for the effects of ocular stray light from the lens, subjects older than 40 yr with a clear crystalline lens were measured and compared with those with pseudophakia. No statistically significant difference was found between the two groups. Increased rod density difference contrasts sharply with an earlier reported decrease in this parameter for foveal cones. The slowing of the regeneration rate is a phenomenon common to rods and cones. It may be a result of a gradual metabolic dysfunction of the retinal pigment epithelium in older subjects. PMID- 1894469 TI - Coryneform group A-4 endophthalmitis. An experimental animal model. AB - Diphtheroids, members of the coryneform family of bacteria, increasingly have been recognized as the cause of serious ocular diseases. After isolation of coryneform group A-4 from two patients with delayed endophthalmitis after cataract extraction and intraocular lens implantation, 10(7) organisms were injected into the vitreous of seven New Zealand white rabbits, producing endophthalmitis in all eyes inoculated. Coryneform group A-4 subsequently was isolated in six of seven eyes receiving 10(7) organisms, proving Koch's postulates. Five of these seven eyes were treated with a single dose of intravitreal gentamicin, and three eyes remained culture positive. Eyes inoculated with 10(5) or 10(2) coryneform group A-4 organisms had transient anterior chamber and vitreal inflammation; all vitreous cultures were negative. These studies demonstrate that coryneform group A-4 endophthalmitis can be reproduced in an animal model and that gentamicin may not sterilize an eye infected with this organism. Future studies are needed to determine the optimum antibiotic regimen for treatment of this type of endophthalmitis. PMID- 1894468 TI - Morphologic effects of bacteriochlorin a and light in vivo on intraocular melanoma. AB - To study the development of tissue and cell damage, the early morphologic changes induced by photodynamic therapy (PDT) with the new photosensitizer bacteriochlorin a (BCA) were investigated in Greene hamster melanoma implanted in the anterior eye chamber of white rabbits up to 24 hr after BCA-PDT, using light and electron microscopy. Immediately after BCA-PDT, intracellular spaces were enlarged, and blood vessels were clotted with swollen erythrocytes. By electron microscopy, it was found that some mitochondria had fused inner and outer membranes, and the cristae mitochondriales were affected. With time, the severity of the tissue and cell damage increased, leading to almost complete tumor necrosis after 24 hr. The direct mitochondrial damage and the vascular damage induced by BCA-PDT probably both contribute to tumor necrosis. PMID- 1894470 TI - Analysis of immunosuppressive properties of iris and ciliary body cells and their secretory products. AB - The anterior chamber of the eye is an immunosuppressive microenvironment as shown experimentally by immune privilege, anterior chamber-associated immune deviation, and inability to display local delayed-type hypersensitivity responses. It recently was reported that both the aqueous humor and the cells of the iris and ciliary body (I-CB) have immune inhibitory properties in vitro, suggesting that these components of the anterior segment might contribute to the unique properties of this microenvironment. To explore the cellular sources of immunosuppressive factors in the anterior chamber, cultures of I-CB cells were established from normal eyes of BALB/c mice. Supernatants were harvested from these cultures and assayed in vitro for their ability to inhibit T-lymphocyte activation. It was found that I-CB cell-derived supernatants profoundly suppressed alloantigen-driven T-cell proliferation (mixed lymphocyte response) and interleukin-2 production by a T-cell hybridoma that responds to stimulator cells bearing I-Ad. The inhibitory activity of I-CB supernatants did not appear to be related to prostaglandins; supernatants of I-CB cells cultured with indomethacin retained their suppressive properties, as did supernatants to which neutralizing antiprostaglandin E2 antibodies had been added. Moreover, suppression by I-CB supernatants was not relieved by antibodies specific for transforming growth factor-beta, even though this cytokine is known to be present in normal aqueous humor. Thus, the identity of the suppressive factor(s) in cultured I-CB cell supernatants remains elusive. Finally, by separating I-CB cell suspensions into bone marrow-derived (T-200-positive) and those not derived from bone marrow (parenchymal) subpopulations with a fluorescence-activated cell sorter, it was determined that the inhibitory activity of I-CB cell suspensions was produced by parenchymal, rather than hematogenous, cells. It is proposed and discussed that inhibitory factors and cytokines secreted by parenchymal I-CB cells contribute to the immunosuppressive qualities of the anterior chamber. PMID- 1894471 TI - The significance of complement in proliferative vitreoretinopathy. AB - Complement is the principal effector arm of antibody-mediated allergic response and plays a central role in the pathogenesis of many immunologic disorders. The possible pathophysiologic importance of complement was examined in the development of proliferative vitreoretinopathy (PVR). Vitreous aspirates from patients with idiopathic PVR (n = 21) and traumatic PVR (n = 15) were examined for total vitreal protein (TVP) and complement components C3, C3d, C4, and C1q fixed immunoglobulins using enzyme-linked immunosorbent assay (ELISA), sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and western blotting. The TVP, C3 components, and factor C4 were elevated significantly in diseased vitreous. The C3-TVP and C4-TVP ratios showed no difference between traumatic and idiopathic PVR. A C4 index to estimate the rate of intraocular C4 synthesis had a mean value of 3.2 (n = 15). The increased relative amount of C3d reflected complement activation in diseased vitreous. The negative values in normal human serum and plasma and in patient plasma samples (n = 15) indicated a local reaction in the eye. The authors found C1q-fixed immunoglobulin G; this may be the cause of complement activation by the classic pathway. These findings support the opinion that the cause of PVR may be based partly on an autoimmune reaction against ocular structures. PMID- 1894472 TI - Effect of mismatches for major histocompatibility complex and minor antigens on corneal graft rejection. AB - The importance of minor histocompatibility genes in corneal graft rejection was investigated using a model that simulates the major histocompatibility complex (MHC) and minor mismatches of the human allograft more accurately than previous animal models. DA(RT1a) x LEW(RT1(1]F1 hybrid rats were backcrossed to LEW, and the backcross generation were used as corneal graft recipients. Female DA(RT1a) strain animals were used as donors throughout. As in humans, the MHC disparity (a to 1) between each donor-recipient pair could be controlled; minor mismatches were variable and unknown. The MHC haplotype of each backcross individual (either homozygous l/l) or heterozygous a/l) was determined. Depending on this haplotype, the transplanted DA cornea was either matched or mismatched with the recipient for MHC antigens. The average proportion of minor disparate loci was 50%, although this was variable and unknown from recipient to recipient. Some animals of each MHC type were sensitized with three subcutaneous DA strain skin grafts at intervals of 2 weeks. Prior sensitization caused more rapid corneal graft rejection in both MHC mismatched (P less than 0.001) and matched (P less than 0.01) animals. All animals in the two MHC-mismatched groups (sensitized, 26; unsensitized, 17) and most in the MHC-matched groups (sensitized, 25 of 27; unsensitized, all 13) rejected their grafts. The MHC matching resulted in a greater range of survival times, although the difference in survival in unsensitized animals between matched and mismatched groups was not significant (unsensitized, P greater than 0.05; sensitized, P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1894473 TI - Maturation of the corneal endothelial tight junction. AB - Apical tight junctional formation of the rabbit corneal endothelium was examined by freeze-fracture analysis and measurement of paracellular permeability to 5(6) carboxyfluorescein. Freeze-fracture analysis indicated that apical tight junction formation of the rabbit corneal endothelium is a dynamic process. At birth, there are few tight junctional strands present and a minimal barrier for paracellular diffusion. As the rabbit matures, a more complex network of anastomosing tight junctional strands begins to encircle the cell perimeter under the apical folds. However, even in the mature animal (3 months), there are discontinuities and free ends in the network, thus suggesting that the barrier is not complete even at this stage. Paracellular permeability measurements using 5(6)-carboxyfluorescein as a tracer corroborate these anatomic findings. Endothelial paracellular flux measurements steadily decrease as the rabbit matures from birth to young adult. This indicates that the tight junctional network is increasing in complexity and progressively limiting the flow of substances through the intercellular space. PMID- 1894475 TI - A comparison of neodymium: yttrium aluminum garnet and diode laser transscleral cyclophotocoagulation and cyclocryotherapy. AB - The cyclodestructive effects of cyclocryotherapy and of the neodymium:yttrium aluminum garnet (Nd:YAG) and diode laser transscleral cyclophotocoagulation were investigated in phakic and pseudophakic cadaver eyes using a modified Miyake posterior-view technique and light microscopy. Cyclocryotherapy to -80 degrees C was applied with a 2.5-mm diameter tip, 1 and 2 mm from the limbus. Freezing at the ciliary processes was evident after 10-15 sec and reached a diameter of 3-4 mm by 30 sec. No visible changes were evident grossly in the ciliary processes, crystalline lens, or intraocular lens. Histologically increased separation of cells was observed. Effective noncontact Nd:YAG and diode laser applications to the ciliary processes were observed grossly as tissue blanching and shrinking and pigment dispersion. This effect was obtained by aiming 0.5-1.0 mm behind the limbus at a 1-mm defocus using 4 J of energy for the Nd:YAG and 1.2 J for the diode laser. The diode laser spot size did not affect the tissue response. No damage was observed in the crystalline or intraocular lens with either type of laser. Histologic changes using both lasers were coagulation necrosis with fragmentation and detachment of the ciliary body epithelium. This study suggested that the gross and histologic thermal effects produced by the diode and Nd:YAG laser were similar in the ciliary body. Also, at the time of surgery, these cyclodestructive procedures potentially cause little alteration of the crystalline or intraocular lens. PMID- 1894474 TI - Type IV collagen and corneal epithelial adhesion and migration. Effects of type IV collagen fragments and synthetic peptides on rabbit corneal epithelial cell adhesion and migration in vitro. AB - Type IV collagen, a 500-kilodalton (alpha 1)2(alpha 2)1 heterotrimer with noncollagenous domains (NC1) is the major molecule in most basement membranes in the body. In addition to its structural role as scaffolding, type IV collagen is involved in promoting adhesion and migration of various cell types in vitro, including rabbit corneal epithelial cells. This study assessed the effect of purified proteolytic fragments of type IV collagen and selected synthetic peptides derived from the alpha 1 and alpha 2 chains that are related to the adhesion and directed migration of dissociated primary cultured rabbit epithelial cells. Two homologous peptides (HEP-1 and HEP-2) derived from alpha 1 and alpha 2 NC1 regions were found to promote epithelial cell adhesion. A peptide (HEP-3) derived from an interruption of the triple helix of type IV collagen was effective in promoting corneal epithelial cell migration in both chemotaxis and haptotaxis assays. The helical fragment of type IV collagen promoted both directed migration and ample adhesion, indicating that there may be at least another moiety in the helical region responsible for cell adhesion. The results with these peptides revealed to some extent how corneal epithelial cells react at the molecular level with type IV collagen. They could serve as the basis for therapeutic agents to modify corneal epithelial behavior in situations of perturbed wound healing. PMID- 1894476 TI - Peripheral color contrast. A new screening test for preglaucomatous visual loss. AB - A new test of peripheral color contrast is described. A high-definition color monitor driven by a personal computer with a graphics interface card displays an annulus subtending 25 degrees at the eye. The color contrast between the annulus and the background can be varied. Forty-five degrees of the annulus is randomly removed in one of four quadrants. Patients are asked to identify the position of the gap while fixating a central spot. The minimum color contrast between annulus and background at which the identification is possible is between 13-16% for the protan, deuteran, and tritan axis in normal subjects. This threshold value changes little with age, refractive error, or pupillary aperture, and test-retest variability is low. Testing one eye takes only 1-2 min. The test was applied to ocular-hypertensive and glaucomatous patients. All patients with glaucoma had thresholds greater than two standard deviations (SD) above the normal mean. In addition, 97% of glaucoma patients had thresholds greater than four SDs, and 95% had thresholds more than five SDs above the normal mean. Most patients with ocular hypertension and clinical signs indicating a low or medium risk of conversion to glaucoma had thresholds under the upper limit of normal. High-risk patients with ocular hypertension fell into two groups. One approximated to normal; the other had elevated thresholds, which in many cases were more than four SDs above the normal mean. The epidemiologic consequences of this test are discussed. PMID- 1894477 TI - Improving the ocular to systemic ratio of topical timolol by varying the dosing time. AB - This study was performed to determine whether the ratio of ocular to systemic absorption of topically applied timolol in the pigmented rabbit can be maximized by varying the time of drop instillation. Twenty-five microliters of 0.65% timolol maleate solutions were instilled into the pigmented rabbit eye at 6 AM, 12 PM, 6 PM, or 12 AM. The time course of timolol concentration in plasma and various eye tissues (conjunctiva, sclera, corneal epithelium, corneal stroma, aqueous humor, iris-ciliary body, and lens) was monitored with the use of reversed phase high-performance liquid chromatography (HPLC). Ocular timolol concentrations were approximately twice as high when the drug was administered at 12 PM than at 6 AM, 6 PM, or 12 AM, whereas timolol concentration in plasma was lowest when the drug was administered at 12 PM. It may, therefore, be possible to maximize the therapeutic index of topically applied timolol by administering the drug at 12 PM. Moreover, the possible influence of dosing time on the extent of ocular and systemic drug absorption must be considered when planning dosing schedules for topically applied ophthalmic drugs. PMID- 1894478 TI - Basic fibroblast growth factor (FGFb) and epidermal growth factor (EGF) receptor messenger RNA production in human lacrimal gland. AB - The polymerase chain reaction (PCR) was used to show that basic fibroblast growth factor (FGFb) and epidermal growth factor (EGF) receptor messenger ribonucleic acids (RNA) are produced in human lacrimal tissue. Transforming growth factor beta-1 (TGF beta-1) messenger RNA was not detected. These results and the previous identification of EGF in the lacrimal gland suggest that EGF could have autocrine or paracrine functions in lacrimal tissue. FGFb could also serve autocrine or paracrine functions in lacrimal gland physiology. It is also plausible that FGFb is released by the lacrimal gland into the tears and that the growth factor may have regulatory effects on the cells of the ocular surface. PMID- 1894479 TI - Discriminating binocular fusion from false fusion. AB - In a series of psychophysical experiments, observers discriminated between briefly flashed stimuli (cosine gratings, cosine plaids) that were either identical to the two eyes (dioptic) or differed between the two eyes (dichoptic). Although dioptic and dichoptic binocular stimuli were perceptually similar, they were distinguishable well above chance at exposure durations too brief for the onset of binocular rivalry. Random variations in display contrast did not alter this pattern of results. These results show that the neural events that signal false fusion of dissimilar monocular stimuli are not equivalent to those that underlie binocular fusion of matched monocular views. PMID- 1894480 TI - Validation of physiologic predictors of successful telescopic spectacle use in low vision. AB - A group of 32 patients with low vision who were considered clinically appropriate candidates for visual rehabilitation with telescopic spectacles were prospectively studied before the first attempted use of these visual aids. Laboratory measurements were made of: (1) rotational head stability in pitch and yaw during quiet standing; (2) sensitivity of visual acuity with telescopic spectacles to imposed yaw head motion; and (3) ocular stabilization reflexes during passive, whole-body rotation in the horizontal plane. Predicted likelihood of successful use of telescopic spectacles was prospectively computed for each patient using the measurement of head stability in the pitch axis and the sensitivity of visual acuity with telescopic spectacles to head motion using a previously described statistical method. Patients were then given telescopic spectacles, and functional success was evaluated in the field at least 6 weeks later by independent masked observers. Although corrected visual acuities did not differ in the 24 patients in whom rehabilitation was successful or in the 8 patients in whom it was not, successful patients had statistically significantly less (P less than 0.05) angular head instability in pitch and yaw, as well as less impairment of visual acuity with telescopic spectacles during head motion. This finding was confirmed in a more clinically homogeneous subgroup of 16 patients who had low vision due to maculopathy. Gains of the 0.1 Hz horizontal vestibulo-ocular reflex (VOR) and visual-vestibulo-ocular reflex (VVOR) with 4X telescopic spectacles did not differ between patients in whom rehabilitation was successful and those in whom it was not.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1894481 TI - The relationship between the stretching capability of the anterior capsule and zonules. AB - The stretching capability of the zonules was studied in 40 human eyes obtained postmortem from 27 patients. A continuous circular capsulorhexis (CCC) (2.2-6.8 mm) was performed, and the lenses were removed by either phacoemulsification (26 eyes) or planned extracapsular cataract extraction (ECCE) (14 eyes). Maximal zonular stretch was calculated as the difference in distance between the ciliary processes and the zonular insertion at rest and after maximal stretch. This zonular stretch test showed that zonules can stretch to a mean distance of 3.82 mm before rupturing. Capsular elasticity was measured in 35 of the eyes by gradually opening a modified caliper until the capsular opening was torn. The ratio between the circumference at rupture and the circumference at rest was used as an index of capsular elasticity. Circumference of the intact capsulorhexis could be enlarged an additional 62% before a radial tear occurred. In most cases, no significant correlation was seen between the capsular and zonular capability to stretch. Maximal zonular stretch decreased significantly with age by approximately 0.5 mm for every 5 yr, whereas capsular elasticity did not show a significant correlation with age. Two eyes with pseudoexfoliation had relatively friable zonules but the capsular elasticity was within normal limits. Patient age is probably the best indicator of the stretching capability of the zonules. PMID- 1894482 TI - Normal change in the foveal cone ERG with increasing duration of light exposure. AB - Foveal cone electroretinograms (ERG) were elicited with a stimulator ophthalmoscope from 24 normal subjects with a 4 degrees stimulus flickering at 42 Hz and centered within a 12 degrees steady surround. The stimulus and surround were presented at retinal illuminances of 4.8 log td and 5.5 log td, respectively, to facilitate visualization of the fundus. Several consecutive averaged responses were evaluated to determine whether increasing duration of light exposure causes an increase in amplitude, as previously found for the full field cone ERG. On average, amplitude increased by 27% over time, and the linear regression of amplitude on recording number accounted, on average, for 42% of the amplitude variability between consecutive responses. Two subjects had amplitudes that were initially subnormal, based on previously published norms, but that value increased to within the normal range in subsequent recordings. These findings show that a significant change in the cone ERG occurs in the fovea with increasing duration of light exposure at these retinal illuminances, and suggest that, when the stimulator-ophthalmoscope is used, consecutive foveal cone ERGs should be obtained from patients with suspected macular disease to avoid a false diagnosis of retinal malfunction. PMID- 1894483 TI - 'Being a good physician is not enough'. PMID- 1894484 TI - We are a 'serving profession'. PMID- 1894485 TI - Trousseau's syndrome. AB - Trousseau's syndrome remains a widely unrecognized and untreated complication of cancer. The clinical spectrum of the coagulopathy extends from uncomplicated superficial thrombophlebitis to life threatening DIC. Due to the absence of specific biochemical markers associated with the hypercoagulable state, this diagnosis is often overlooked. Initial intravenous heparin followed by the chronic administration of subcutaneous heparin will usually prevent thromboembolic recurrence. PMID- 1894486 TI - Society deserves better. PMID- 1894487 TI - Advance directives for medical care. PMID- 1894488 TI - Suicide in Ireland. PMID- 1894489 TI - Torture and the medical profession. PMID- 1894490 TI - Helmets for pedal cyclists. PMID- 1894491 TI - Retinal detachment. PMID- 1894492 TI - Injuries to the head and neck in association footballers. PMID- 1894493 TI - The palpable gallbladder. PMID- 1894494 TI - Cystic fibrosis in adolescents and adults. AB - A cystic fibrosis (CF) clinic for adults was established in 1977. We have reviewed the data on 164 patients who attended between 1977 and 1989. Twenty four patients had died, 11 being over 20 years after time of death. Of the 140 patients still alive, 61% were male and 53% were aged over 20 years. Only 55% were diagnosed by 1 year and 88% by 10 years. Almost all patients had respiratory symptoms and sputum culture yielded Pseudomonas species in 69%. Other respiratory problems included major haemoptysis and pneumothorax, each in 10%. We found a wide range of respiratory impairment among older patients. Among 3 patients aged over 23 years the mean (+/- S.D.) percent predicted FEV1 and FVC were 53.3% (+/- 18%) and 71.4% (+/- 20%) respectively. Mean weight in this group was 92.5% (+/- 14) of predicted. Malabsorption occurred in most patients and meconium ileus equivalent occurred in most patients and meconium ileus equivalent occurred in 34%. Other complications were clinical hepatomegaly (16%), diabetes mellitus (9%) and arthropathy (20%). Most patients were taking continuous antibiotics by mouth (89%) and by nebuliser (48%), beta-2 agonists by inhaler (57%) and oral steroids (29%). Almost all were taking multivitamins, pancreatic replacement therapy and multiple nutritional supplements. The number of CF "bed days" grew 12 fold since 1979 and the mean stay in hospital was double the hospital mean. The economic impact was such that over 1/4 of the annual hospital antibiotic budget was expended on CF patients. PMID- 1894495 TI - Caring for dementia sufferers in the community: the caregivers problems. AB - Twenty-four carers of dementia sufferers were screened for psychological well being and compared with 19 carers of non-demented elderly. Carers of demented relatives showed significantly raised levels of stress on the Relatives' Stress Scale (RSS), and also increased psychiatric morbidity on the 30 item General Health Questionnaire (GHQ-30), when compared with the carers on non-demented relatives. Scores in the behaviour and mood disturbance scale (BMD) were significantly raised in the dementia group of patients, when compared with the non-demented group. However, high scores on the behaviour and mood disturbance Scale for the dementia sufferer were not correlated with increased stress and psychiatric morbidity scores found in the relatives of the patients with dementia. The implications of these findings are discussed. PMID- 1894496 TI - Treatment of chronic varicose ulcers with pulsed electromagnetic fields: a controlled pilot study. AB - To evaluate the efficacy of pulsed electromagnetic fields (PEMF) in healing of chronic varicose ulcers, 19 patients with this condition were included in a double-blind controlled clinical trial. All patients received standard ulcer therapy throughout the duration of the study and were randomly divided into two groups to receive either active or inactive PEMF therapy. Active therapy was provided by the use of a pait of helmholtz coils on a twice weekly basis over a five week period and inactive therapy was provided on an identical regimen with identical coils wound so that no magnetic field was produced when an electric current was passed through them. The clinician and patients were unable to distinguish the active or inactive coils. No statistically relevant difference was noted between the two groups in the healing rates of the ulcer, change in the lower leg girth, pain or infection rates. However there was a trend in favour of a decrease in ulcer size and lower leg girth in the group treated with active PEMF. As PEMF is a novel treatment for chronic varicose ulcers, more work needs to be done to establish treatment parameters and its usefulness in the treatment of this condition. PMID- 1894497 TI - Grosse-Kempf intramedullary nailing of femoral fractures. AB - The Grosse-Kempf nail is a versatile interlocking intramedullary nail with proximal and distal locking. The locking transfixion screws afford additional axial and rotational stability and have expanded the use of intramedullary fixation to include all types of femoral fractures distal to the lesser trochanter and to within 7 cm of the knee joint. Forty consecutive femoral shaft fractures treated by this method have been reviewed. Solid union occurred in 39 cases at six months from surgery. Complications were directly related to technical difficulties and fracture personality. The surgical technique is demanding and requires special expertise training and equipment, but the benefits to the patient are so great that this is now regarded as the method of choice for treating femoral shaft fractures in adults. PMID- 1894498 TI - An unusual case of muscle weakness. PMID- 1894499 TI - Clinico-pathological findings in non-immune hydrops fetalis. AB - Non-immune hydrops fetalis is becoming a relatively more important cause of hydrops as the incidence of rhesus-related hydrops falls. We describe a series of 33 cases, occurring over a 7 year period covering most of the 1980's. We found a very wide range of aetiological factors, but cardiac conditions, both structural and dysrhythmic, formed the largest subgroup (12 cases, 36%). Seven cases (22%) remained idiopathic. Prognosis was very poor, with only 4 infants surviving. Outcome was best in the cases due to intra-uterine supraventricular tachycardia. Nineteen cases were detected antenatally, but except in the cases of fetal tachyarrhythmias, this had little effect on outcome. PMID- 1894500 TI - Irish Cardiac Surgery Register--summary 1989. PMID- 1894501 TI - A large outbreak of salmonellosis and its economic cost. AB - In the summer of 1989, a large outbreak of gastroenteritis occurred in persons attending a barbeque. An investigation was carried out to determine the cause, institute control measures, and to estimate the costs involved in the outbreak. Epidemiological investigation revealed that chicken served at the barbeque was the pecant food, which was confirmed by microbiological investigation. Prompt institution of control measures resulted in early containment of secondary spread. Nevertheless, the total cost of the outbreak amounted to 77,995 pounds. The economic impact of this outbreak was therefore considerable. PMID- 1894502 TI - Low levels of cryofibrinogenaemia and peripheral circulatory dysfunction. AB - Over 12 months of general internal medicine practice in a small community, three premenopausal women, and a man presented with peripheral circulatory complaints. All were found to have cryofibrinogen, a cold-precipitable abnormal fibrinogen complex, in their blood. None had cryofibrinogen levels above 100mg per 100ml. The plasma of 195 other patients were screened. Cryofibrinogen was found in only one of these samples, that of a 23 year old women with active lupus erythematosis. These case reports suggest a relationship between low levels of cryofibrinogenaemia and mild circulatory disorders. PMID- 1894504 TI - Fournier's gangrene. PMID- 1894503 TI - Skeletal tuberculosis. AB - Skeletal tuberculosis is an uncommon form of tuberculosis. During the period 1977 87, the number of cases diagnosed in two Dublin hospitals has remained at a constant level. The present study reports on 36 adults with skeletal tuberculosis and shows more frequent extraspinal involvement than other studies. The long duration of symptoms prior to diagnosis of 10.79 (+/- 8.8) months suggests that tuberculosis is not being considered early in the course of unexplained inflammatory arthritides especially in the elderly patient. The under utilisation of the Mantoux test in diagnosis is also a matter of concern. PMID- 1894505 TI - Obstetrics without an on site paediatrician. PMID- 1894506 TI - Verified causes of failure in the treatment of femoral neck fractures with multiple Knowles pins. AB - The authors examine 152 cases of femoral neck fractures treated with Knowles pins in order to analyze the incidence and causes of nonunion and avascular necrosis. The displaced fractures were all treated with closed reduction, and weight bearing was permitted after 30-45 days. Seventy fractures were followed up after an average of four years. Criteria are proposed for evaluating the quality of both the reduction and the internal fixation. Healing was achieved in all cases of Garden grade I and II fractures; the incidence of avascular necrosis was 4.1%. In the displaced fractures the incidence of nonunion was 15.2% and avascular necrosis 13%. Technical errors in either reduction or internal fixation were present in 50% of the necroses and in 100% of the nonunions. The quality of the reduction was the most important factor in fracture healing, yet an accurate reduction and a valid fixation could not completely overcome the risk of avascular necrosis in the femoral head. PMID- 1894507 TI - Comminuted articular fractures of the distal radius. Results of conservative treatment. AB - Fifty-nine comminuted articular fractures of the distal radius which had received conservative treatment were reviewed after an average of 3 1/2 years. The results -excellent in 15 patients, good in 30, fair in 12, and poor in 2--were closely linked to the quality of the articular reduction. In patients with a residual malalignment greater than 2 mm, a relatively high incidence of both degenerative arthritis (31%) and unsatisfactory results (56%) was found. The presence of a "die punch" fragment often precluded acceptable fracture reduction and was therefore responsible for many poor clinical and radiographic results. The quality of the extraarticular reduction proved to be of little importance to the final outcome. PMID- 1894508 TI - Breakage of the Kuntscher nail in fractures of the femur after healing has occurred. AB - Four cases of breakage of Kuntscher intramedullary nails (AO model) are presented. All 4 nails broke after fracture healing had occurred and all 4 presented breakage of the stem in the same site. In these cases breakage of the nails is not due to instability of the fracture, but always derives from superficial micro-cracks, technologically inevitable, due to defects or irregularities in the metal that expand during load application. PMID- 1894509 TI - Osteochondroma of the cervical spine. AB - The localization of an osteochondroma in the spine is considered a rare occurrence. The authors describe the case of a 37 year-old woman with osteochondroma of the C2 neural arch involving the C1 spinous process. The woman came under observation because of severe loss of neck mobility and was subsequently diagnosed with osteochondroma. Of the preoperative examinations, MRI was more valuable than CT scan for defining the nature and extent of the tumor. Treatment consisted of complete posterior excision of the tumor, including the C1 spinous process and the C2 laminae up to the facets. PMID- 1894510 TI - Osseous anomalies of the craniovertebral junction: a case report. AB - The authors describe the principal anomalies of the craniovertebral junction with particular reference to atlantooccipital fusion. They discuss the case of a female patient with pain and cervical contracture in whom a paracondylar process was revealed. Unless trauma brings it out, this abnormality can go unnoticed. CT scan is the only examination useful for diagnosis. PMID- 1894511 TI - The Doppler stress test for the vertebral arteries. AB - The authors propose a new method of depistage and thorough diagnostic examination of temporary vertigo caused by extrinsic compression of the vertebral arteries. This method is easy to execute, noninvasive, reliable, and relatively inexpensive. Its purpose is to confirm diagnosis by documenting criteria that are visible and reproducible. PMID- 1894512 TI - Quadricepsplasty with the V-Y incision in total knee arthroplasty. AB - For over 8 years the authors have used the inverted V-Y incision of the quadriceps, a modification of the Coonse and Adams approach, in total knee arthroplasty (TKA) with serious reduction of flexion, ankylosis, or limited mobility of the patella because of previous operations. This procedure not only allows easy and complete exposure, but improves the range of flexion without incision-related complications. Detailed results of a consecutive series of 16 knee arthroplasties are presented. PMID- 1894513 TI - Survivorship of the Total Condylar I prosthesis: Results of a series of 100 total knee arthroplasties. AB - The Total Condylar knee prosthesis was employed at our institution from April 1975 to October 1986; currently the posterior stabilized type is in use. The results of 100 knee arthroplasties using the Total Condylar I prosthesis, 83 of which were reviewed after an average of 7 1/2 years (maximum 14), were rated good or excellent in 82% of the subjects. Three cases were considered failures due to infection or aseptic loosening. According to the survivorship analysis, there is a 14-year success rate of 93%. PMID- 1894515 TI - The Onik method of automated percutaneous lumbar diskectomy (A.P.L.D.). Criteria of selection, technique, and evaluation of results. AB - The Onik method of automated percutaneous lumbar diskectomy is a new type of percutaneous surgery for the treatment of herniated lumbar disk. Candidates for this procedure should be carefully evaluated on the basis of precise clinical criteria and instrumental diagnosis. The goal is to select patients in whom excellent results can be achieved, recognizing the limitations as well as the merits of the technique. The surgical approach is described and the potential difficulties are discussed, since this technique must be performed with precision and without trauma in order to obtain good results. The clinical results of 500 patients treated by the Onik method of automated percutaneous lumbar diskectomy are reported. The follow-up period ranged from 6 months to 2 1/2 years. The patients were divided into three groups according to the strength of the indication for A.P.L.D.; the quality of the result is reported for each group. PMID- 1894514 TI - Third-degree lesions of the external compartment of the ankle: results of conservative treatment. AB - Ankle sprains are one of the most common lesions of the musculo-skeletal system. In some sports they are the most common reason that athletes seek medical care. For this reason many publications are dedicated to this subject, and specifically to the treatment of lesions of the external compartment, which account for about 85% of all ligamentous lesions of the ankle (O'Donoghue, 1958). The treatment of these lesions is very controversial. Some orthopedists propose early surgical treatment to restore normal healing with minimal functional lengthening. Others favor conservative treatment, while still others recommend functional treatment with the objective of accelerating the recovery of proprioceptive reflexes affected by the ligamentous lesion as well as stimulating healing by movement. The authors' diagnostic and therapeutic approach to lesions of the external compartment of the ankle is explained with special reference to lesions in athletes, who must be guaranteed perfect joint stability in order to tolerate the intense stress of sports activity without danger of relapse. PMID- 1894516 TI - Surgical treatment of vertebral deformity due to myelomeningocele. AB - Surgical treatment of vertebral deformity due to myelomeningocele has always presented important technical problems. Many complications, the foremost of which pseudarthrosis and infection, are reported in the literature. The authors discuss 14 patients with vertebral deformity from myelomeningocele who were treated with different surgical methods and reviewed after an average of eight years. The only conclusion that can be drawn on the basis of both the literature and the present study is that posterior surgery alone is incapable of guaranteeing stable correction over time for severe deformity. Combined anterior and posterior surgery with spinal fusion up to the sacrum yields better results, and the patient is not required to wear a corset afterward. PMID- 1894517 TI - Retention of the posterior cruciate ligament in total knee arthroplasty. AB - The importance of the preservation of the posterior cruciate ligament in total knee arthroplasty is analyzed from a biomechanical, clinical, and functional standpoint. Using clinical and radiographic criteria, the authors assess posterior cruciate ligament validity in a selected group of 31 of 45 total knee arthroplasties (PCA prosthesis) reviewed at least 18 months after the operation. Sixty-eight percent of the replaced knees, which were divided into two groups on the basis of preoperative deformity, had a functional posterior cruciate ligament. In view of these results the authors are satisfied with the prosthetic model they adopted, which was designed not only to preserve the posterior cruciate ligament, but also, by virtue of its special shape, to compensate in the event of ligament insufficiency. PMID- 1894518 TI - Total hip replacement with the "Biodirect" cementless prosthesis. AB - The authors discuss the biomechanical features of the "Biodirect" cementless prosthesis, which has been used for over 6 years in the treatment of displaced femoral neck fractures. The long-term clinical and radiographic results of this study were generally favorable and seemed directly proportional to the accuracy of the implantation technique. PMID- 1894520 TI - Internal and external fixation in complex diaphyseal and metaphyseal fractures of the humerus. AB - The treatment of diaphyseal and metaphyseal fractures of the humerus is often controversial, especially when these fractures are complex and/or unstable (i.e. comminuted, segmental, or with a butterfly fragment). The authors review the indications, advantages, and disadvantages of various open and closed procedures, concluding that a combination of internal and external fixation is a valid treatment for these fractures. The purpose of the external fixation is immediate stabilization of the fracture, which is difficult if not impossible with intramedullary internal fixation alone. Internal fixation devices (Rush rods or "anchor" nails introduced by closed means) make it possible to align the fracture, facilitating application of the external fixator, and at the same time promote rapid healing. Fractures treated by this method healed in an average of 2 1/2 months, without residual functional limitations of the shoulder or elbow. PMID- 1894519 TI - Diaphyseal and metaphyseal hemiresection with autograft reconstruction in the treatment of lowgrade tumors of the long bones. AB - The authors discuss seven cases of parosteal tumors treated conservatively by diaphyseal and metaphyseal hemiresection with cortical autograft reconstruction. This treatment yielded excellent clinical and functional results without having to resort to resection and arthrodesis or prosthetic replacement. The slow growth and low malignancy of these tumors make the use of this technique possible even at the risk of local recurrence, which, if discovered early, can still be treated by further conservative procedures. PMID- 1894522 TI - Review of neurobehavioral assessment tools. AB - Behavioral, cognitive, and memory deficits are frequently observed sequelae of brain injury. Yet in most critical care settings, neurologic assessment is limited to evaluation of arousal, pupillary response, orientation, and motor capability. Behavior, cognition, and memory are not routinely evaluated. Several brief, bedside assessment tools are reviewed. All may be used in the critical care setting to evaluate the type and extent of residual deficits in the neurologically impaired patient. Nursing implications, based on the evaluation of deficits, are also discussed. PMID- 1894521 TI - Herniation of the lumbar intervertebral disk in teenagers. AB - Thirty-five teenagers treated for herniation of the lumbar intervertebral disk are reviewed. In almost all cases the subjective symptoms were very minor compared to the physical signs. Radiologic examination revealed a high incidence of lumbosacral anomalies and, less frequently, anomalies of the dural sac or nerve roots. Conservative treatment failed to improve the symptoms in all cases, while surgery and various closed techniques (chemonucleolysis, percutaneous diskectomy) were successful. PMID- 1894523 TI - Effect of lung hyperinflation and endotracheal suctioning on heart rate and rhythm in patients after coronary artery bypass graft surgery. AB - We examined the effect of lung hyperinflation and suction on PaO2, heart rate, and rhythm in patients after coronary artery bypass graft surgery (N = 26). Three lung hyperinflation breaths, at one of five randomly ordered volumes (tidal volume, 12 cc/kg, 14 cc/kg, 16 cc/kg, or 18 cc/kg of lean body weight) were delivered, by a ventilator (fraction of inspired oxygen 1.0), followed by 10 seconds of continuous suction. Lung hyperinflation and suctioning were repeated three times. Repeated-measures analysis of variance revealed a statistically significant increase (p = 0.000) in PaO2 immediately after the third suction pass, which was volume dependent (p = 0.009). A statistically significant (p less than 0.001) increase in heart rate from baseline occurred over the three lung hyperinflation-suctioning sequences that was not volume dependent. The mean increase in heart rate was 6.8 beats/min. The majority of rhythm changes for lung hyperinflation and suctioning were from normal sinus rhythm to sinus tachycardia. Suction was associated with a greater incidence of rhythm (53.9%) and arrhythmia (80.8%) changes. The most frequent arrhythmia was premature atrial contraction. PMID- 1894524 TI - Pulmonary embolism associated with the act of defecation. AB - Pulmonary embolism associated with the act of defecation has not been well described in the medical literature. We report our experience with deep vein thrombosis in patients who had a pulmonary embolism triggered by the act of defecation. In these individuals the embolization of peripheral thrombus appeared to have resulted from the performance of the Valsalva maneuver and its effects on peripheral blood flow and intrathoracic pressures. In addition, the important role of nursing personnel in recognizing and diagnosing this disorder as well as in initiating prophylactic measures directed against the development of thromboembolic disease is discussed. PMID- 1894525 TI - Acetazolamide in the treatment of metabolic alkalosis in critically ill patients. AB - Metabolic alkalosis is a common acid-base disturbance in critically ill patients. In many patients correction of fluid and electrolyte status does not fully correct the metabolic derangement. In this study we examined the effect of 500 mg of intravenous acetazolamide, after correcting for fluid and electrolyte abnormalities, on the acid-base status of 30 ventilated patients. In all patients studied there was a fall of total serum bicarbonate; the mean reduction at 24 hours was 6.4 mmol/L, with a normalization of the base excess and pH. The onset of action was rapid (within 2 hours), and the maximal effect occurred at a mean of 15.5 hours, although there was wide variation. The effect of acetazolamide was still apparent at 48 hours. No adverse effects were noted. We conclude that in patients with metabolic alkalosis, once fluid and electrolyte abnormalities have been corrected, acetazolamide is an effective and safe form of therapy with a quick onset and long duration of action. PMID- 1894526 TI - Lovastatin-associated rhabdomyolysis. AB - Lovastatin is a new drug that has become popular for the treatment of patients with hyperlipidemias. Rhabdomyolysis is a well-documented and potentially dangerous side effect of lovastatin therapy. Critical care nurses should be aware of the symptoms and treatment of rhabdomyolysis. Patients receiving lovastatin should be instructed to report muscle pain or weakness and dark urine immediately. It should be determined whether patients are at risk for development of rhabdomyolysis from other causes so that lovastatin can be withheld. Early diagnosis and treatment can prevent serious complications in patients with lovastatin-induced rhabdomyolysis. PMID- 1894527 TI - Clinical decision making of critical care nurses managing computer-simulated tachydysrhythmias. AB - The purposes of this study were to describe the clinical decision making of critical care nurses managing computer-simulated tachydysrhythmias and to assess the major sources of error related to the management of two tachydysrhythmias: atrial flutter and ventricular tachycardia. In this descriptive study, 142 critical care nurses each completed four computerized clinical simulations (two atrial flutter and two ventricular tachycardia). Simulation performance was measured by proficiency score (comparison with expert performance), patient outcome (cure or die), and amount of data collected before the first intervention. Mean proficiency scores were 51% for atrial flutter and 35% for ventricular tachycardia. Thirteen percent of the atrial flutter and 35% of the ventricular tachycardia simulations ended in patient death. Failure to recognize ventricular tachycardia and unfamiliarity with second- and third-line treatments were major sources of error. Medication errors were the cause of death in 87% of the simulations ending in patient death. These results document the need for emphasis on dysrhythmia management in the critical care curriculum. PMID- 1894528 TI - Effect of level of patient acuity on clinical decision making of critical care nurses with varying levels of knowledge and experience. AB - This study is an examination of the effect of patient acuity on the clinical decision making of critical care nurses (N = 68) completing two computerized clinical simulations. Ventricular tachycardia represented the high-acuity situation and atrial flutter the lower-acuity situation. Clinical decision making was measured by proficiency score, patient outcome (cure or die), and amount of data collected. Analyses of variance were conducted to examine proficiency score and the amount of data collected. Fisher's exact test and the McNemar test of homogeneity of proportions were used to examine patient outcome. In the atrial flutter simulation, proficiency scores were higher (p = 0.000), more dysrhythmias were cured (p less than 0.005), and more data were collected (p = 0.040). Experienced and inexperienced nurses did not differ on proficiency score; however, inexperienced nurses collected more data (p = 0.048) and cured fewer atrial flutter simulations (p = 0.040). Nurses certified in advanced cardiac life support had higher proficiency scores (p = 0.033) and collected fewer data (p = 0.048). PMID- 1894529 TI - Overview of work-related hazards in nursing: health and safety issues. AB - Nurses working in hospital environments are exposed to a number of occupational health hazards. For five categories of hazards we present research-based documentation of potential and actual health-related problems, and avenues for health promotion and prevention of exposures. Both personal and organizational responsibilities for self-health protection are addressed. PMID- 1894530 TI - Burnout, job stress, anxiety, and perceived social support in neonatal nurses. AB - Forty-nine nurses working in neonatal intensive care were surveyed by using measures of job stress, burnout, anxiety, and perceived social support. On the Maslach Burnout Inventory, they scored in a moderate range of burnout for emotional exhaustion and depersonalization and in a high range of burnout for sense of personal accomplishment. Stepwise regression analyses revealed that higher job stress scores, higher anxiety scores, perception of less supervisor (head nurse) support, and less experience were associated with higher burnout subscale scores. PMID- 1894532 TI - Nosocomial enterococcal urosepsis in a compromised host. PMID- 1894531 TI - Common reactions to transfusions. AB - A blood transfusion is a special kind of transplantation, with the transfer of living tissue from one person to another. Reactions can occur with as little as 10 to 15 ml of incompatible blood. The onset of a reaction may be misleading or delayed, and its detection requires astute assessment. Responsibility for recognition of a transfusion reaction lies with the transfusionist, who is often a nurse. The following types of response can occur: hemolytic reactions, transfusion-induced graft-versus-host disease, hemoglobinuria, purpura, fever, circulatory overload, thrombophlebitis, urticaria, hyperkalemia, asymptomatic hemoglobinuria, pulmonary edema, and allergic and anaphylactic reactions. Critical care nurses need to be aware of the dangers of blood and blood product transfusions and to be prepared to react quickly. PMID- 1894533 TI - Unraveling the mystique of power analysis. AB - Power analysis provides one method for assessing the efficacy of alternative research designs. The purpose of this article is to simplify the methods for calculating power analysis to determine an adequate sample size. Although attention to type I errors (alpha error) is prevalent among nurse researchers, there is less appreciation for research problems resulting from a type II error. Without the a priori examination of the power of the test of significance, there is no assurance that the sample is sufficient to discern significant differences. Formulas for calculating effect size are provided for t tests, correlations, chi square, analysis of variance, and regression. Examples of calculating the effect size by using four different statistical tests based on research studies are presented: t tests with unequal variance between groups, chi-square, an analysis of variance, and regression. Power analysis is an additional procedure to ensure that the sample size is adequate for the research project about to be undertaken. PMID- 1894534 TI - Crisis and ethical dilemmas: who will care for the rural nurse? AB - The critical care nurse who works in the small rural community faces the unique experience of indistinct personal and professional roles. Established relationships in the rural community place the critical care nurse at risk of becoming a victim when ethical and crisis events arise. PMID- 1894535 TI - Family needs and nursing responses to critically ill patients. PMID- 1894536 TI - Early hospital arrival and treatment of patients with acute myocardial infarction: practice management and your role in thrombolytic therapy. Introduction. PMID- 1894537 TI - Early hospital arrival and treatment of patients with acute myocardial infarction: practice management and your role in thrombolytic therapy. Boston, Massachusetts, May 12, 1991. PMID- 1894538 TI - Overview: rationale of thrombolysis in treating acute myocardial infarction. AB - Treatment of coronary thrombosis with thrombolytic agents was first introduced in the 1950s. Clinical trials, primarily with streptokinase during the 1960s and 1970s, addressed the effects of thrombolysis on mortality rates after acute myocardial infarction, but were inconclusive and largely ignored. In 1976, Chazov et al. from the Soviet Union demonstrated that intracoronary streptokinase could produce prompt recanalization of a totally occluded infarct-related artery. In 1980, DeWood et al. demonstrated that 87% of patients with classic Q-wave myocardial infarction had total occlusion from coronary thrombosis of the infarct related artery when studied during the first 4 hours of their infarction and that 65% of these arteries were still occluded when patients were studied between 12 and 24 hours after infarction. These observations stimulated renewed interest in thrombolytic therapy for acute myocardial infarction. Mortality trials have subsequently demonstrated that agents such as recombinant tissue plasminogen activator, streptokinase, and anisoylated plasminogen streptokinase activator complex remarkably reduce early mortality rates among patients with acute myocardial infarction when treatment is instituted within the first 6 hours of infarction. Benefit has yet to be demonstrated, however, in patients with acute myocardial infarction characterized by ST-segment depression. This whole area is currently under study by the TIMI investigators. TIMI-3B is a mortality study in which patients with either non-Q-wave myocardial infarction or unstable angina with rest pain are randomly assigned to receive either tissue plasminogen activator or placebo. Results of this trial will help us in the future to determine the appropriate role of thrombolytic therapy in treating acute ischemic syndromes other than transmural myocardial infarction. PMID- 1894539 TI - Clinical management of patients receiving thrombolytic therapy. AB - Rapid delivery of thrombolytic therapy to suitable patients with acute myocardial infarction can limit myocardial damage and reduce the risk of death. This requires an emergency department team approach following a written protocol to initiate thrombolytic therapy within 45 minutes of the patient's arrival at the emergency department. Nurses and physicians caring for patients with acute myocardial infarction must be aware of inclusion and exclusion criteria, drug preparation, dosage and administration, recommended adjunctive therapies, and potential complications associated with pharmacologic thrombolysis. All patients with acute myocardial infarction should be carefully screened for their potential for receiving thrombolytic therapy with a favorable benefit/risk ratio. PMID- 1894540 TI - Delays in the treatment of acute myocardial infarction: an overview. AB - Delays in treatment of acute myocardial infarction prevent a substantial portion of patients from receiving maximal benefit from reperfusion therapy. Median delay between onset of symptoms and arrival at the hospital is 2 to 4 hours. Average time between arrival at the hospital and initiation of thrombolytic therapy is 84 minutes. Approximately 50% of patients hospitalized for suspected acute myocardial infarction do not use the emergency medical service system. Delay before treatment can be divided into several components: patient delay, emergency medical service delay, and hospital delay. Factors contributing to delay in each component and possible approaches to decreasing these delays are discussed. The effects of treatment delay on prognosis and future care-seeking behavior of patients hospitalized with suspected acute myocardial infarction are also discussed. PMID- 1894541 TI - Treatment-seeking behavior among those with signs and symptoms of acute myocardial infarction. AB - Significant delays in seeking definitive treatment for the signs and symptoms of acute myocardial infarction increase morbidity and mortality. In most studies, delay times average more than 4 hours. The following variables are associated with increased delay: a medical history of angina, diabetes mellitus, or hypertension; older age; black race; seeking advice from a family member or a physician; symptom onset on a weekday; and attempts at self-treatment. Variables associated with reduced delay times are the following: pain recognized as cardiac in origin, hemodynamic instability, severe chest pain, younger age, and consultation with a coworker. Surprisingly, patients who have already experienced a myocardial infarction are just as likely to delay as patients who have not had this experience. These findings provide direction for developing and testing patient and family interventions, establishing community education programs, and reducing patient delay in response to the signs and symptoms of acute myocardial infarction. PMID- 1894542 TI - Role of emergency medical services. AB - For thrombolytic therapy to be effective in the treatment of acute myocardial infarction, the patient must enter the health care center delivery system in an efficient manner. Some entry delays are due to patient decisions and interactions with others. In the United States, prehospital care is delivered by a variety of different systems, varying from public service types such as fire-department based to private types of service. These personnel vary in level of training from paramedics with a high level of training to Emergency Medical Technicians Ambulance with basic training (first aid), even less in some areas. The training should be upgraded so that training as an emergency medical technician with the ability to defibrillate would be the minimum level for emergency ambulance personnel; wherever economically and logistically feasible, ambulance personnel should be paramedics. Although the 911 emergency telephone system exists in some areas, there is no centralized, universal system for access, causing confusion and delays in obtaining care in critical situations such as cardiac arrest. There is a need for a national emergency number--911--with the ability to identify the calling number and address. Since dispatchers have little medical dispatch training, needed instructions are not given to the caller, which can reduce the patient's chance of survival. Trained dispatchers are needed to dispatch resources efficiently and to offer assistance until trained rescuers arrive. Ambulances are inefficiently located in some areas of the United States, slowing response to the patient.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1894543 TI - The role of hospital delivery systems in the treatment of patients with acute myocardial infarction: rural hospital setting. AB - Discussions on the use of thrombolytic therapy include when is the best time for administration, where is the best place for administration, and who is the most appropriate to begin the administration. Rapid triage and intervention for patients with suspected acute myocardial infarction are special challenges in rural communities. To evaluate the possibility of instituting rapid, "golden hour" treatment for the patient with acute myocardial infarction, rural health care resources must be reviewed. Changes in the health care environment and access to emergent care for the patient with acute myocardial infarction directly affect any treatment. Timely interventions depend on available personnel, appropriate clinical protocols, and regional network systems. PMID- 1894544 TI - Problems faced by the urban emergency department in providing rapid triage and intervention for the patient with suspected acute myocardial infarction. AB - Widespread application of thrombolytic therapy has increased the importance of rapid triage and intervention for the patient who seeks treatment in the emergency department (ED) for suspected acute myocardial infarction. It has been suggested that all patients with acute myocardial infarction who might benefit from thrombolytic therapy should receive treatment within the first "golden hour" of arrival at the hospital ED. Busy urban medical centers, particularly public hospitals serving a large proportion of indigent patients, face special challenges in attempting to meet this goal. ED overcrowding, in part caused by patient "dumping," and diminishing governmental financial support have created an environment in which rapid triage and treatment are difficult. Because only 4% to 5% of all patients who are seen in the ED with chest pain actually require thrombolytic therapy, there is negative reinforcement for the triage nursing staff. The busy urban ED environment also creates greater litigation potential for the physician and nurse. Problems created by the busy ED environment can be minimized by providing adequate nursing staff, standing orders and protocols for evaluation of the patient with chest pain, equipment for an immediate electrocardiogram, and a thrombolytic drug stock in the ED. Hospital administrators must recognize the unique problems created in the ED when inpatient beds are unavailable. The hospital must also have efficient bed turnover and a community-wide plan for dealing with patients when the ED "closes" to incoming ambulance traffic. Governmental entities must recognize the consequences of their actions in curtailing health care benefits for those who cannot afford care in private hospitals. PMID- 1894545 TI - Productivity and profitability of twin births in beef cattle. AB - Data from 1,277 single and 85 twin calvings, occurring in both spring and fall from 1980 through 1987, were used to examine the productivity and profitability associated with twin births in beef cattle. Pregnancies in pure and crossbred cattle resulted from both AI and embryo transfer. Cows and calves were confinement-housed. Cows were individually fed to specification. Calves were given ad libitum access to creep feed and those born in 1986 and 1987 were fed to slaughter. The influence of birth number of gestation length, total calf birth and weaning weights, lactation yield, and cow fed intake during both the dry and lactating periods were examined. Twin-bearing cows had their gestation length shortened by 6.4 d (2%); yielded 25.5 (59) and 186.0 kg (73%) more weight of calf at birth and weaning, respectively; had lactation yield and lactation feed intake increased by 25 and 20%, respectively; and had precalving (dry) period feed intake no different from their single-bearing counterparts (P = .12). Postweaning growth was not different for single and twin calves (P = .50); twin gain, relative to initial size, was higher. Feedlot feed intake of twins was 85% of that for singletons (P = .20). Twins were 90% of singleton live weight at slaughter and yielded 93% of singleton hot carcass weight (P = .12). Twins were slightly older and significantly leaner at slaughter. Returns less feed costs showed twin births to be associated with increased profit for cow-calf programs. Returns less feed and overhead costs were higher for twin calves than for singles in the feedlot. PMID- 1894546 TI - Effect of pre- and postweaning management system on the performance on Brahman crossbred feeder calves. AB - During a 3-yr period (1986 through 1988), 117 calves (57 steers and 60 heifers) from the same genetic base and reared under four distinct preweaning management systems were weaned in the fall and transported from Uvalde, TX to El Reno, OK (800 km). Weaning weight and transportation shrink varied more from year to year than among preweaning treatments. Postweaning performance was not affected by preweaning treatment. After a 28- to 32-d receiving period the calves were blocked by sex and previous preweaning treatment, then randomly assigned within block to graze winter wheat forage (WHEAT) or dormant tall-grass native range (GRASS). The WHEAT group gained more (P less than .01) weight than the GRASS group during the winter (November to March), but when both groups were allowed to graze spring wheat pasture (March to June) the GRASS group gained more (P less than .01) weight than the WHEAT calves. During the subsequent finishing phase the GRASS calves were more (P less than .01) efficient than the WHEAT calves in converting DM to gain. Because cattle were slaughtered at the same degree of finish, no differences were noted in carcass characteristics among the pre- or postweaning treatments. Feeder calves exposed to a restrictive period of growth during the postweaning period gained weight more rapidly in a subsequent forage based stockering system and were more efficient in a grain-based finishing system than nonrestricted calves. PMID- 1894547 TI - Evaluation of between- and within-breed variation in measures of weight-age relationships. AB - Variation between- and within-breeds was evaluated for accretion of weight from birth to 7 yr of age and hip height at 7 yr for 1,577 cows sired by Angus, Brahman, Brown Swiss, Charolais, Chianina, Gelbvieh, Hereford, Jersey, Limousin, Maine Anjou, Pinzgauer, Sahiwal, Simmental, South Devon, and Tarentaise and from either Angus or Hereford dams. Parameters from Wt = A (1 - Be-kt) were estimated by nonlinear regressions and provided estimates of mature body weight (A) and rate of weight accretion relative to change in age (k) for each cow. Actual weight at birth, linear adjusted weights at 200, 365, and 500 d of age, ratios of these weights to mature weight, and height at the hip at 7 yr were analyzed. Beyond 20 mo, weights were adjusted to a constant condition score within breed of sire. Variance and covariance components were derived for breed (sigma 2 b), sires within breed (sigma 2 s), and progeny within sire (sigma 2 w). For all traits, the sigma 2 b estimate of genetic variance ranged from two to four times greater than the variance component for sigma 2 s. Between-breed heritabilities were .91 +/- .27 and .54 +/- .17 for A and k, respectively. Estimates of within breed heritability for these two traits were .61 +/- .11 and .27 +/- .09. Estimates, both between- and within-breed, of the genetic correlation between A and k were moderate to large and negative; those between A and weights at 200, 365, and 500 d and height at maturity were large and positive. Selection for immediate change in measures of growth would be most effective among breeds. Sufficient direct genetic variation exists between breeds to enhance breed improvement of growth characters through breed substitution. Greater opportunity to alter the shape of the growth curve exists through selection for within-breed selection than through breed substitution. PMID- 1894548 TI - Direct responses to selection for increased litter size, decreased age at puberty, or random selection following selection for ovulation rate in swine. AB - Nine generations of selection for high ovulation rate were followed by two generations of random selection and then eight generations of selection for increased litter size at birth, decreased age at puberty, or continued random selection in the high ovulation rate line. A control line was maintained with random selection. Line means were regressed on generation number and on cumulative selection differentials to estimate responses to selection and realized heritabilities. Genetic parameters also were estimated by mixed-model procedures, and genetic trends were estimated with an animal model. Response to selection for ovulation rate was about 3.7 eggs. Response in litter size to selection for ovulation rate was .089 +/- .058 pigs per generation. Average differences between the high ovulation rate and control lines over generations 10 to 20 were 2.86 corpora lutea and .74 pigs (P less than .05). The regression estimate of total response to selection for litter size was 1.06 pigs per litter (P less than .01), and the realized heritability was .15 +/- .05. When the animal model was used, the estimate of response was .48 pigs per litter. Total response in litter size to selection for ovulation rate and then litter size was estimated to be 1.8 and 1.4 pigs by the two methods. Total response to selection for decreased age at puberty was estimated to be -15.7 d (P less than .01) when data were analyzed by regression (realized heritability of .25 +/- .05) and -17.1 d using the animal model. No changes in litter size occurred in the line selected for decreased age at puberty. Analyses by regression methods and mixed-model procedures gave similar estimates of responses and very similar estimates of heritabilities. PMID- 1894549 TI - Evaluation of performance-tested boars using a single-trait animal model. AB - Data structure designs for breeding value estimation of performance-tested boars using mixed-model methodology were compared. Computer models were based on estimates of parameters from the literature and from results of a survey of test station managers. Results were compared using accuracy (the correlation of true and estimated breeding values) and prediction error variance (PEV). The single trait animal model included a fixed effect due to station-season, a random effect due to breeding value for ADG or backfat, and a random error term. Family size, number of families per test, and relationships among animals within and across tests were varied. Prediction error variance decreased faster for small families than for large ones as number of families increased, but increasing numbers of animals per pen was most important, especially if test size was optimized. With no other genetic ties, full-sibs were much more accurately evaluated than half sibs. Designs that included sire ties among families within a station-season resulted in increased PEV. Increasing the number of full-sibs and(or) increasing the number of families per test would help to optimize PEV and correct this problem. Tying station-seasons with the relationship matrix improved the average accuracy of predicted breeding values. Placing full-sibs in different stations resulted in the greatest accuracy of evaluation, but a large number of half-sib (sire) ties resulted in comparable accuracies. Half-cousin ties did not improve accuracy of evaluation but could result in significant genetic progress by increasing the selection differential. PMID- 1894550 TI - Output/input differences among nonpregnant, lactating Bos indicus-Bos taurus and Bos taurus-Bos taurus F1 cross cows. AB - Nonpregnant F1 crossbred cows, progeny of either Hereford (H) or Angus (A) dams and sired by Brahman (Bm), Sahiwal (Sw), Pinzgauer (Pz), H, or A sires, were fed to maintain initial weight while rearing Charolais (C)-sired progeny for a period of 126 d in drylot commencing at about 48 d postpartum. Cow-calf pairs were assigned to equalize cow age, calf sex, and breed of cow's dam among three replicate pens of approximately 12 pairs each. Cows and calves were weighed every 2 wk and feed intake was adjusted to minimize change in cow weight. Metabolizable energy (ME) consumption for zero cow weight change was estimated by regression. Milk production was estimated by weight-suckle-weigh at 58, 85, 125, and 170 d of lactation. Calf gain (GAIN, kg) relative to cow weight (CWT1, kg) was higher (P less than .01) for calves from Bm-X (139.5/585) and Sw-X (132.2/534) than for calves from Pz-X (127.2/552) and HA-X (116.9/547) cows. Estimated mean daily production of milk was 7.40, 7.15, 7.28, and 6.37 kg for the Bm-X, Sw-X, Pz-X, and HA-X, respectively. Total cow ME intake (TMEcow) for breed groups ranked (P less than .05) with cow size and milk production, and calf creep-feed intake (FMEcalf) was inversely related to estimated milk intake. Proportion of total feed ME (TMEcow+calf) consumed by calves was higher (P less than .05) for HA-X cows (18%) than for the others (14%). Total efficiency of calf gain in weight (GAIN/TMEcow+calf) was 11% greater (P less than .05) for crossbred cows of Bos indicus X Bos taurus (Bm-X, Sw-X) than for Bos taurus X Bos taurus (Pz-X, HA-X) cows (35 vs 32 g/Mcal) in the 126-d lactation period. PMID- 1894551 TI - Characterization of relative growth of empty body and carcass components for bulls from a five-breed diallel. AB - Slaughter and carcass data were obtained on 197 bulls produced in a diallel involving Angus, Brahman, Hereford, Holstein and Jersey that were slaughtered at either 6, 9, 12, 15, 18, 24, or 30 mo of age. Bulls were given ad libitum access to a 72% TDN diet on an individual basis from 6 mo of age until slaughter. Empty body weight (EBWT) was determined as the sum of the weights of blood, hide, hard drop, soft drop (minus contents of the digestive tract), and carcass weight (CWT), which were recorded at slaughter. Carcass protein (CPROT) and fat (CFAT) were based on weights and chemical analyses of lean and fat tissue and bone of the carcass. Empty body protein (EBPROT) and fat (EBFAT) were based on weights and chemical estimates of the components of the empty body. Growth of EBWT, EBPROT, EBFAT, CWT, CPROT, and CFAT relative to either live weight (LWT), EBWT, or CWT were investigated using the allometric equation. Breed-type differences existed (P less than .01) for the growth of EBWT relative to LWT. Comparisons of general combining abilities revealed that Angus, Hereford, and Jersey generally had lower maturing rates of EBWT relative to LWT and that Brahman and Holstein had higher maturing rates. Across breed-type, relative growth rates indicated that fat and protein were later-maturing components relative to LWT, EBWT, or CWT, which implies that other components mature relatively earlier. Relative maturing rates of components studied were not important in explaining differences in body composition that have been previously reported for these breed-types. PMID- 1894552 TI - Genetic and environmental trends for litter size in swine. AB - Best linear unbiased predictors (BLUP) of breeding values for additive direct and additive maternal genetic effects were estimated from 3,944 purebred Yorkshire and Landrace first-parity litters recorded on the Quebec Record of Performance Sow Productivity Program and born between 1977 and 1987. Breeding values for gilts, dams, and sires were estimated using an individual animal model for measures of litter size of total number born (NOBN), number born alive (NOBA), and number weaned (NOWN). Environmental trends were estimated from average herd year solutions, and genetic trends were estimated by regression of estimated breeding value on year of birth. Environmental trends were positive for all traits in both breeds but were significant only for NOWN in Landrace (.051 +/- .021 pigs/yr). Genetic trends were very small but were mainly negative for direct breeding value and combined direct and maternal breeding value. Significant estimates of genetic trends (P less than .05) were observed only within the Yorkshire breed, and these ranged from -.012 +/- .004 to .004 +/- .002 pigs/yr. PMID- 1894553 TI - Heritabilities and genetic correlations for postweaning growth and feed intake of beef bulls and steers. AB - Data from studies conducted at Miles City, MT and Lethbridge, AB were pooled to evaluate genetic and environmental variation in feed intake (MEI), growth rate (ADG), MEI-to-gain ratio (M/G), final weight (FWT), and fat thickness (FAT). A total of 124 sires with an average of 4.25 progeny each were represented in the data. Restricted maximum likelihood methods were used to estimate within and between paternal half-sib estimates of variance and covariance. Heritabilities and genetic, phenotypic, and environmental correlations with inference to populations at 365 d of age were calculated from the estimates. Heritabilities were as follows: ADG, .38 +/- .16; MEI, .45 +/- .17; M/G, .26 +/- .15; FWT .25 +/ .15; and FAT .52 +/- .17. The genetic correlation of MEI with ADG was large (.73 +/- .13) and antagonistic to genetic improvement of M/G through selection for ADG. Efficient genetic improvement in M/G was found to depend on using either MEI or an indicator of composition of gain as selection criteria in addition to ADG. Selection to improve M/G using an index that included FWT and FAT, in addition to MEI and ADG, resulted in greater predicted response in ADG and lesser predicted response in MEI than the index of ADG and MEI alone. PMID- 1894554 TI - National sheep improvement program: age adjustment of weaning weight. AB - Lamb weaning weights at 30 +/- 14, 60 +/- 28, and 90 +/- 28 d were used to evaluate the effect of birth weight on the linear adjustment of weaning weight to a constant age and the effect of deviations from target dates on the accuracy of linear age adjustment. The data consisted of 13,501 birth weights, 3,721 30-d records, 10,988 60-d records, and 3,285 90-d records from the National Sheep Improvement Program data base for the Dorset, Polypay, Rambouillet, Columbia, Hampshire and Suffolk breeds. The effect of using constant vs actual birth weights in a standard linear age adjustment was evaluated using various sex, type of-birth, and breed type constants. Product moment and rank correlations indicated that a constant birth weight should be used when the actual birth weight is not known, but the choice of constant makes little difference in average bias or maximum adjustment error. The linear age adjustment procedure and the optimal age range for recording weaning weight were examined using a model including effects for contemporary group, sex, type of birth and rearing, age of dam, and breed. The linear age adjustment did not remove the effect of age for the small breed type (Dorset, Polypay, and Rambouillet breeds) at 30 d and the large breed type (Columbia, Hampshire, and Suffolk breeds) at 60 d for age ranges greater than +/- 7 d (P less than .01) but was adequate for all lambs weaned at 30 +/- 7 d, 60 +/- 7 d, and 90 +/- 28 d of age. PMID- 1894555 TI - Breed effects and heterosis in advanced generations of composite populations for growth traits in both sexes of beef cattle. AB - Heterosis effects for birth weight, ADG from birth to weaning, 200-d weight, ADG from weaning to 368 d, 368-d weight, 368-d height, 368-d condition score, and 368 d muscling score (males only) were evaluated separately for each sex in F1, F2, and combined F3 and F4 generations in three composite beef cattle populations. Breed effects were evaluated for the nine parental breeds (i.e., Red Poll [R], Hereford [H], Angus [A], Limousin [L], Braunvieh [B], Pinzgauer [P], Gelbvieh [G], Simmental [S], and Charolais [C]) that contributed to the three composite populations (MARC I = 1/4 C, 1/4 B, 1/4 L, 1/8 H, 1/8 A; MARC II = 1/4 G, 1/4 S, 1/4 H, 1/4 A; and MARC III = 1/4 R, 1/4 P, 1/4 H, 1/4 A). Breed effects were significant for all traits evaluated. The large differences among breeds for growth and size traits in combined additive direct and additive maternal genetic effects (Gi + Gm) provide an opportunity to use genetic differences among breeds to achieve and maintain optimum additive genetic (breed) composition for growth and size traits to match cattle genetic resources to a wide range of production and marketing situations. Combined individual and maternal heterosis was significant in the F1, F2, and combined F3 and F4 generations for each composite population and for the mean of the three composite populations in both sexes for most of the traits evaluated. In both sexes, heterosis retained in combined F3 and F4 generations was greater (P less than .05) than expected based on retained heterozygosity for birth weight, ADG from weaning to 368 d, and for 368-d weight and did not differ (P greater than .05) from expectation for other traits. These results support the hypothesis that heterosis in cattle for traits related to growth and size is due to dominance effects of genes. PMID- 1894556 TI - Ovulation rate and twinning rate in cattle: heritabilities and genetic correlation. AB - Repeated measures of ovulation rate on puberal heifers should be an effective way to select for increased twinning rate. A reliable estimate of the genetic correlation between ovulation and twinning rates is needed to implement such selection and to predict its efficiency. Restricted maximum likelihood was used to estimate genetic correlations from subsets of data collected from the twinning project at the Roman L. Hruska U.S. Meat Animal Research Center. The animal model included numerator relationships among the animals and fixed effects of year season of measurement, age at measurement, and birth group. Genetic correlations between averages of ovulation rates for three, four, five, six, seven, and eight estrous cycles and the occurrence of twins were, respectively, .62, .76, 1.00, 1.00, 1.00, and .98 based on observations on 200 to 325 puberal heifers. Corresponding phenotypic correlations ranged from .06 to .26. Genetic correlations between ovulation rate in a single estrous cycle and occurrence of twins were .38, .98, and .98, respectively, for 323, 430, and 283 cows with ovulation rate measured after measurement of twinning, in the same season as measurement of twinning, and more than 1 yr before measurement of twinning. Phenotypic correlations were .00, .07, and .00. Genetic and phenotypic correlations among ovulation rates at six consecutive estrous cycles averaged, respectively, .66 and .12 for 610 heifers. Heritabilities for ovulation rates in individual cycles averaged .16. No evidence of negative environmental covariance between ovulation rates in adjacent cycles was found. These results support the approach of indirectly selecting for twinning rate by measuring ovulation rates in estrous cycles of puberal heifers. PMID- 1894557 TI - Genetic parameters for testosterone production in boars. AB - Data were collected in 1982 through 1989 from 66 sires and 358 Duroc boars. Testosterone production was measured from peripheral blood samples before (PRE) and after (POST) GnRH challenge. Additionally, data were collected on testes length at 168 d (TL168), testes width at 168 d (TW168), testes volume at 168 d (TVOL), birth weight (BWT), average daily gain (ADG), days to 104 kg (DAYS104), and backfat adjusted to 104 kg (FAT). Overall means for these traits were 24.6 ng.ml-1.h-1, 75.7 ng.ml-1.h-1, 12.3 cm, 11.6 cm, 422.0 cm3, 1.5 kg, .5 kg, 189.3 d, and 18.5 mm, respectively. Son-sire regressions were used to calculate genetic parameters. Heritabilities for PRE, POST, TL168, TW168, TVOL, BWT, ADG, DAYS104, and FAT were .37, .26, .33, .34, .33, .21, .42, .35, and 0, respectively. Moderately favorable genetic correlations were obtained for PRE and POST with growth measurements. Large positive genetic correlations were present for both PRE and POST with TL168, TW168, and TVOL, and testes measurements had large positive genetic correlations with growth traits. Selection for testes size or testosterone production should be equally effective. However, it seems that selection for testes size would result in larger changes in measures of growth than selection for testosterone. This study suggests that testes measurements are good predictors of both basal and challenge testosterone levels. Selection for increased testis size or increased testosterone levels would be expected to enhance growth. PMID- 1894558 TI - Cell-mediated immune function in lambs chronically treated with dexamethasone. AB - Crossbred ewe and wether lambs were individually stanchioned in environmentally controlled rooms at 20 degrees C. On d 0, lambs were treated with .04 mg of dexamethasone (DEX; n = 10)/kg of BW or given an equal volume of saline vehicle (SAL; n = 10). Treatment was repeated every 48 h for 14 d. Samples of blood were obtained by puncture of the jugular vein on d 0 (before treatment), 2, 4, 7, 10, and 14. Total and differential leukocyte numbers, lymphocyte blastogenic responses to mitogens, and in vitro production of interleukin-2 (IL-2) were determined. No treatment x day interaction was noted for any of the experimental end points (P greater than .10); therefore, within-day comparisons between DEX- and SAL-treated lambs were not made. However, over all 14 d, DEX-treated lambs had increased (P less than .05) numbers of lymphocytes (6.5 +/- .4 vs 5.1 +/- .4 x 10(3) cells/microliters for SAL) and monocytes (.8 +/- .1 vs .6 +/- .1 x 10(3) cells/microliters for SAL), and these increases contributed to an increase (P less than .01) in total leukocytes (11.2 +/- .5 vs 9.1 +/- .5 x 10(3) cells/microliters for SAL). Lymphocyte blastogenic responses to mitogens were not affected by DEX treatment. Production of IL-2 was reduced (P less than .05) for DEX- (.90 +/- .12 units/ml) compared with SAL-treated lambs (1.27 +/- .13 units/ml). The data suggest that continued treatment of lambs with DEX may result in a modest reduction in production of IL-2, but mitogen-stimulated blastogenic responses of lymphocytes are not reduced by DEX treatment. PMID- 1894559 TI - Cortisol, growth hormone, and testosterone concentrations during mating behavior in the bull and boar. AB - Two experiments were conducted to evaluate peripheral concentrations of cortisol (C), growth hormone (GH), and testosterone (T) in bulls and boars during mating and to correlate mating behaviors with endocrine secretion in the presence of an estrous female. In Exp. 1, six sexually inexperienced mature bulls were bled every 15 min for 2 h before and 2 h after a 30-min exposure to a single, restrained, estrous cow; sampling occurred every 5 min during exposure. In Exp. 2, six sexually experienced boars were bled similarly before and after exposure to a sow and every 5 min during a 15-min exposure to a freely moving, estrous sow. Behavioral events recorded during exposure to a female included the following: flehmen responses (bulls only), mounts, penis extensions, intromissions, ejaculations, and time to first mount and first ejaculation. Of the six bulls, four completed at least one service (intromission + ejaculation), and three of six mounted the estrous cow eight or more times. Completion of one or more services resulted in significant elevations in serum C and GH concentrations, but not T concentrations, during the exposure period. Bulls mounting eight or more times also experienced significant elevations in C concentrations during exposure. Three of six boars completed at least one service. Servicing and mounting the sow fewer than five times were both associated with significant elevations in serum C concentrations. Serum concentrations of T were also elevated as a result of exposure to an estrous sow. Collectively, these data support the suggestion that specific events during natural mating activity can alter endocrine secretions of C and GH in bulls and C and T in boars. PMID- 1894560 TI - Isolation and culture of fetal porcine myogenic cells and the effect of insulin, IGF-I, and sera on protein turnover in porcine myotube cultures. AB - Porcine myogenic cells isolated from 50 to 55-d porcine fetuses were frozen and stored in liquid nitrogen until they were needed to establish cultures. Approximately 75.8 +/- .59% of the clonal cultures established from these frozen stocks produced myotubes and 60.8 +/- 2.3% of the nuclei in differentiated mass cultures were in myotubes. Differentiated cultures contained higher levels of creatine phosphokinase activity than undifferentiated cultures. Additionally, differentiated cultures incorporated [35S]methionine into putative myosin heavy chain, alpha-actinin, and actin more rapidly than did undifferentiated cultures. Insulin, insulin-like growth factor I, and sera stimulated total protein synthesis rate and decreased total protein degradation rate in myotube cultures. Based on our initial characterization, we believe that we have developed an effective and practical procedure for isolating and culturing fetal porcine myogenic cells. PMID- 1894561 TI - Physical and chemical components of the empty body during compensatory growth in beef steers. AB - The composition of carcass and noncarcass tissue growth was quantified by serial slaughter of 26 Angus x Hereford crossbred steers (initial age and weight 289 +/- 4 d and 245 +/- 4 kg) during continuous growth (CON) or compensatory growth (CG) after a period of growth restriction (.4 kg/d) from 245 to 325 kg BW. All steers were fed a 70% concentrate diet at ad libitum or restricted levels. Homogenized samples of 9-10-11th rib and noncarcass tissues were analyzed for nitrogen, fat, ash, and moisture. Growth rate from 325 to 500 kg BW was 1.54 and 1.16 kg/d for CG and CON steers. The weight of gut fill in CG steers was 10.8 kg less (P less than .05) before realimentation and 8.8 kg more (P less than .10) at 500 kg BW than in CON steers. The allometric accretive rates for carcass chemical components relative to the empty body were not affected by treatment. However, the accretive rates for CG steers were greater (P less than .01) for noncarcass protein (.821 vs .265), noncarcass water (.861 vs .507), and empty-body protein (.835 vs. .601) than for CON steers. Final empty-body fat was lower (P less than .001; 24.2 vs 32.4%) and empty-body protein higher (P less than .001; 16.6 vs 14.8%) in CG steers than in CON steers. Consequently, net energy requirements for growth (NEg) were approximately 18% lower for CG steers. We conclude that reduced NEg requirements and changes in gut fill accounted for most of the compensatory growth response exhibited in these steers. PMID- 1894562 TI - Applications of a multiphasic growth function to body composition in pigs. AB - A multiphasic growth function was used to relate growth of body components to phases of total growth for pigs. Each phase of growth was characterized by asymptotic weight, age at maximum gain, and duration. Age at maximum gain and duration were expressed as a ratio and assumed constant for all phases. One application involved weights of total DM predicted directly with a diphasic function and indirectly with monophasic functions of fat-free DM and fat. Another involved weights of carcass side predicted directly with a diphasic function and indirectly with monophasic functions of offal + muscle + bone and fat + skin. Components were grouped on age at maximum gain. There was good agreement for asymptotic weight between body components and phases, and general agreement for age at maximum gain and for duration, except for carcass weights. A multiphasic growth function may provide a way to examine fat-adjusted weight in living animals because growth of fat appears as a late phase in a multiphasic description of total body growth. PMID- 1894563 TI - National beef tenderness survey. AB - To determine the average tenderness and sensory ratings of beef subprimal cuts sold in retail cases across the United States, retail cuts were purchased through typical retail outlets in 14 metropolitan cities and transported to Texas A&M University for sensory and Warner-Bratzler shear analysis. The overall mean shear force for all cuts was 3.65 kg, and the mean shear force values for chuck, rib, loin, and round cuts were 3.72, 3.36, 3.17, and 4.31 kg, respectively. No difference (P greater than .05) in tenderness was detected among the cuts from the rib. Mean palatability ratings and shear force values of top loin steaks were similar to those of rib cuts. Top sirloin steaks were tougher (P less than .05) and received the lowest sensory ratings compared with other loin cuts. Approximately two to three times as many round and chuck steaks had shear force values in excess of 4.6 kg compared with their roast counterparts. In all cases, roasts tended to be more tender than steaks from the same subprimal source. USDA Choice chuck retail cuts, compared to Select and No-roll chuck cuts, had approximately 10% fewer cuts with shear force values in excess of 4.0 kg. More work is needed to improve meat tenderness, primarily for retail cuts from the round and chuck primals. Future research must investigate the interaction of antemortem and postmortem factors associated with variation in beef tenderness. PMID- 1894564 TI - Effects of age, castration, and season on difficulty of pelt removal in lambs. AB - Sixty-four white-faced rams and wethers were dressed with the aid of a commercial pelt puller. The effects of age, castration, and season on difficulty of pelt removal and pelt damage were evaluated. Lambs were divided into two age groups (5 and 12 mo) within gender (ram and whether) and season (spring and fall). A greater force (P less than .05) was required to remove pelts from rams than from wethers in both 5- and 12-mo-old groups. Older lambs slaughtered in the fall required more force (P less than .05) to remove their pelts than did those slaughtered in the spring, but differences by season did not exist for 5-mo-old lambs. The difference between rams and wethers in percentage of live weight that was closely shorn pelt weight was not significant (P greater than .05). The area of grain crack in the flank expressed as a percentage of total area of the skin was lower (P less than .05) for skins from 5-mo-old lambs and ram lambs than it was for skins from 12-mo-old lambs and wether lambs, respectively. Factors involved in difficulty of pelt removal in ram lambs included crosscut shoulder weight, fat firmness, and carcass weight. Difficulty of pelt removal in wether lambs was best predicted by including crosscut shoulder weight and bodywall thickness in multiple regression equations. PMID- 1894565 TI - Effects of dietary canola seed and soy lecithin in high-forage diets on performance, serum lipids, and carcass characteristics of growing ram lambs. AB - Phospholipids (soy lecithin) are important in the emulsification of lipids and may be able to escape the rumen and influence the absorption of fatty acids in the small intestine. The objectives of this study were to determine the influence of dietary canola seed (high in unsaturated fatty acids) and soy lecithin in high forage diets on performance, serum lipid metabolites, and carcass characteristics of growing ram lambs. Forty-three Hampshire- or Suffolk-sired ram lambs were weaned at 60 d of age (average 23.6 kg BW) and assigned to a 2 x 2 factorial arrangement of the following treatments (% of DM): 1) basal diet (control = BAS); 2) BAS with 6% whole canola seed (CS); 3) BAS with 4.9% deoiled soy lecithin (SL); and 4) BAS with 6% CS and 4.8% SL (CSSL). The BAS diet consisted of 70% forage and 30% concentrate and contained 15% CP and 2.2 Mcal of ME/kg. Lambs had ad libitum access to their diet to an average final BW of 52.1 kg. Lambs were bled by jugular venipuncture on d 0, at 4-wk intervals, and 1 d before slaughter. Dry matter intake was not affected by treatment; however, energy intake (Mcal of ME/d) was greater (P less than .01) for lambs fed SL. Feeding SL and(or) CS to growing ram lambs increased (P less than .02) serum lipid concentrations. Carcasses from lambs fed SL were fatter, as evidenced by greater dressing percentage and subcutaneous fat thickness. Feeding CS to growing lambs had little effect on performance and carcass characteristics compared with feeding SL, which resulted in greater energy intake and fatter carcasses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1894566 TI - Measuring suitability of soybean products for early-weaned pigs with immunological criteria. AB - Two trials were conducted to determine the suitability of soybean products for baby pigs. Weanling pigs (n = 40 and 48 in Trials 1 and 2, respectively) were infused orally (6 g/d) with dried skim milk, soybean meal (SBM, 48% CP); soy protein concentrate, moist extruded soy protein concentrate, or soy protein isolate from d 7 to 12 of age. Pigs were then fed a diet containing the same protein source for 1 (Trial 1) or 2 (Trial 2) wk after weaning (d 21 of age). To avoid exposure of pigs to soybean proteins, the dams of pigs were fed a corn-corn gluten meal-based diet supplemented with lysine and tryptophan from d 109 of gestation. All pigs in Trial 1 were killed at 28 d of age, and samples of ileal digesta and small intestine were obtained. In Trial 2, the soy protein isolate was not included, and all pigs were fed a diet containing 4% soybean oil and 1.25% lysine for the last 3 wk of the trial. Growth performance, skin-fold thickness, after intradermal injection of extracts of the corresponding proteins, and anti-soy immunoglobulin G (IgG) titers were measured. Results indicated that pigs fed diets containing SBM had lower (P less than .05) villus height and xylose absorption but higher (P less than .05) serum anti-soy IgG titers and increased skin-fold thickness compared with the mean of pigs given milk and all other soy treatments.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1894567 TI - Extender and centrifugation effects on the motility patterns of slow-cooled stallion spermatozoa. AB - Slow-cooled stallion spermatozoa, with and without seminal plasma removed by centrifugation, were diluted in Kenney's extender (KE) containing nonfat dry skim milk with glucose and antibiotics or in KE supplemented by adding a modified high potassium Tyrode's medium (KMT). Four ejaculates from each of four stallions were collected and divided factorially across these four treatments. Percentage of motile sperm, path velocity, and linearity immediately after treatment (0 h) and after storage at 4 degrees C for 24, 48, and 72 h were evaluated objectively by use of a HTM-2030 sperm motility analyzer. Stallions were a significant source of variation (P less than .01) throughout. After sperm had cooled, effects of stallion, extender, centrifugation, and their interactions were all found to be significant (P less than .01). The motility at 0, 24, 48, and 72 h for centrifuged KE was 74, 47, 39, and 24%; for uncentrifuged KE was 76, 56, 50, and 37%; for centrifuged KMT was 76, 75, 72, and 64%; and for uncentrifuged KMT was 80, 50, 26, and 13%, respectively. The extender x centrifugation interaction, after 24, 48, and 72 h of storage, accounted for half or more of the variation. Whereas centrifugation of semen extended in KE seemed to be harmful to sperm, motility of sperm extended in KMT after centrifugation was remarkably conserved for 72 h and was superior to all other treatments (P less than .05). This extender is promising for preserving liquid stallion semen when it must be transported before use in artificial insemination. PMID- 1894568 TI - Poor reproductive response of anestrous Suffolk ewes to ram exposure is not due to failure to secrete luteinizing hormone acutely. AB - Twenty Polypay-sired ewes (Group P) and 14 Suffolk ewes (Group S) were bled at 48 h intervals for 10 d beginning on April 6, 1989, and the serum was assayed for progesterone to determine which ewes were anestrous; 9/20 Group P ewes were anestrous, compared with 14/14 Group S ewes (P less than .001). Catheters were placed into the jugular vein of anestrous ewes from both breed groups (eight of Group P, seven of Group S), and samples of serum were collected at 12-min intervals for 4 h. Then, the ewes were exposed to mature, intact rams, and additional samples were taken at 12-min intervals for 4 h after ram exposure. The serum was later analyzed to determine the secretion of LH in response to ram introduction. After the acute bleeding period, all Group P and Group S ewes were commingled and exposed to a ram continuously for 42 d. Samples of serum were collected thrice weekly and analyzed for progesterone to monitor ovulatory response to ram introduction through the 42-d period. In addition, breeding activity and lambing data were recorded. When all Group P ewes were compared to Group S ewes, a greater proportion (P less than .001) of Group P ewes were mated (20/20 vs 3/13; one Group S ewe died during the 42-d mating period) by the end of the 42-d period and more (P less than .001) ewes lambed in the fall (17/20 Group P vs 2/13 Group S).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1894569 TI - Development of a culture system for bovine granulosa cells: effects of growth hormone, estradiol, and gonadotropins on cell proliferation, steroidogenesis, and protein synthesis. AB - The objectives of the present studies were 1) to develop a culture system that has the positive effect of serum on granulosa cell attachment and allows subsequent expression of hormonal effects in serum-free medium and 2) to determine the effect of insulin, epidermal growth factor (EGF), estradiol (E2), and growth hormone (GH) on growth, steroidogenesis, and(or) protein synthesis of bovine granulosa cells. Cells from small (1 to 5 mm) and large (greater than 8 mm) follicles were collected from cattle and cultured for either 4 or 6 d. When cells from small follicles were cultured, insulin (5 micrograms/ml) increased (P less than .05) cell numbers (cells x 10(5)/well) severalfold compared with controls. Alone, EGF (10 ng/ml), FSH (200 ng/ml), LH (200 ng/ml), E2 (2 micrograms/ml), or GH (0 to 1,000 ng/ml) had no effect on cell numbers. However, when included with insulin, 30, 100, and 300 ng/ml of GH increased (P less than .05) granulosa cell numbers on d 4 of culture. Insulin alone increased (P less than .05) progesterone production (ng.10(5) cells-1.24 h-1) by severalfold on d 4, but EGF, FSH, LH, or GH alone had no effect and E2 inhibited progesterone production. In the presence of insulin, FSH and GH (100 ng/ml) increased (P less than .05) progesterone production on d 4 of culture, whereas EGF (10 ng/ml) elicited a decrease (P less than .05) in production. In cells from both sizes of follicles, GH (300 ng/ml) increased synthesis of cellular proteins (greater than 10 kDa). In cells from only large follicles, LH (200 ng/ml) decreased synthesis and secretion of proteins (greater than or equal to 3.5 kDa). These results support the hypothesis that GH may have direct effects on bovine ovarian function. PMID- 1894570 TI - Transfer of porcine embryos after 3 days of in vitro culture. AB - Two experiments were conducted to determine the viability of porcine embryos transferred after long-term in vitro culture. In Exp. 1, four-cell embryos were kept in culture for 120 h. Embryos that were exposed to fresh culture medium every 12 h survived better than embryos kept in the same medium throughout the culture period. In Exp. 2, four- and eight-cell embryos were cultured in vitro for 72 h before transfer to estrus-induced recipient gilts. Each gilt received, on average, 19 embryos. If recipients were synchronous with donors 3/32 (9%) recipients remained pregnant with an average of 4.0 +/- .6 viable young. If the sexual cycle of the recipients was 24 h behind that of the donors the pregnancy rate was 18/34 (53%) with 4.4 +/- .5 viable young. Average embryo survival rate for the two groups was 1.8 and 12.5%, respectively. A 24-hourly medium replacement during the in vitro culture period had no significant effect on transfer results. When transferring freshly collected blastocysts, pregnancy rate, number of viable young and survival rate of embryos were 6/10 (60%), 7.8 +/ 1.4, and 23.9% for synchronous recipients and 7/10 (70%), 9.3 +/- 1.8, and 32.9% for asynchronous recipients, respectively. Recipients with very high plasma progesterone levels or numerous follicular cysts at the time of transfer were less likely to remain pregnant than others. PMID- 1894571 TI - Separation of mounting-inducing pheromones of vaginal mucus from estrual heifers. AB - There is evidence that mucus of the female bovine genital tract contains pheromones that induce physiological and behavioral responses in other animals. To study these pheromones, vaginal mucus was collected from heifers either at estrus or during diestrus. The mucus was then applied to the hindquarters of the same animal during diestrus or to the hindquarters of herdmates during diestrus. The behaviors of the treated animal and its herdmates were then observed. To attempt to isolate the mounting-inducing substance, mucus was dialyzed or separated on ion-exchange resins. Diestrous heifers to which their own estrual mucus has been applied were nearly always mounted by herdmates (P less than .01). But, heifers to which another's estrous mucus had been applied were not mounted. This suggests that vaginal mucus contains not only estrus-related pheromones, but also individual distinctive odors. The dialyzable fraction of vaginal mucus and the neutral fraction, prepared by ion-exchange chromatography of the dialyzable solution of vaginal mucus, had a mounting-inducing activity on the herdmates, as did the application of an animal's own vaginal mucus. These findings suggest that mounting-inducing pheromones are relatively low molecular weight, neutral substances. PMID- 1894572 TI - Responses of yearling steers to different stocking rates on a subtropical grass legume pasture. AB - Despite potential benefits, limitations of individual tropical legumes have restricted development of sustainable grass-legume pastures in tropical and subtropical regions. Sowing mixtures of complementary legumes may overcome limitations of individual species. Responses of yearling steers grazing a mixture of three tropical legumes with bahiagrass (Paspalum notatum Flugge) were evaluated at three stocking rates under continuous grazing. Carpon desmodium (Desmodium heterocarpon [L.] DC.), which is persistent under grazing but often difficult to establish, was combined with the short-lived legumes aeschynomene (Aeschynomene americana L.) and phasey bean (Macroptilium lathyroides [L.] Urb.). Diet composition, as determined by microhistological analysis of fecal samples, and animal performance were evaluated in three grazing periods: summer 1987 and spring 1988 (2.0, 3.5, and 5.0 steers/ha) and summer 1988 (3.0, 5.3, and 7.5 steers/ha). Stocking rate did not affect percentage of the selectively grazed legumes, aeschynomene and phasey bean, in the diet. Average daily gain decreased linearly (P less than .05) with increased stocking rate, as is typical for grass pastures. Aeschynomene and phasey bean contributed to diets during the first summer, and carpon desmodium contribution was greater in the second summer. These results indicate that this pasture mixture can provide legume herbage from aeschynomene and phasey bean in the year of sowing and from carpon desmodium thereafter. Over the range of grazing pressures obtained, legume responses were generally consistent; thus, optimizing stocking rate for gain per hectare or for economic returns can be targeted without additional constraints to maintain the contribution of these legumes to grazing livestock. PMID- 1894573 TI - Growth, body composition, and visceral organ mass and metabolism in lambs during and after metabolizable protein or net energy restrictions. AB - Three trials were conducted to assess effects of metabolizable protein and NE deficiencies on changes in body composition, organ mass and metabolism, and animal growth performance during restriction and realimentation. Growth of lambs was restricted to achieve no change in BW for periods of 5 to 6 wk by limiting intake of metabolizable protein or NE. In Trial 1, changes in body composition and visceral organ mass and metabolism during restriction were compared to unrestricted controls using 36 lambs. Trial 2 was designed to investigate changes in growth, body composition, and visceral organs during restriction and realimentation periods using 44 lambs. Trial 3 was limited to evaluation of differences in performance and carcass characteristics of previously restricted and unrestricted ram lambs (15 total). Results of Trial 1 indicated that liver weights were decreased with nutrient restrictions. Body protein mass was conserved in energy-restricted (ER) lambs and lost in protein-restricted (PR) lambs. Fat was mobilized at similar rates for PR and ER lambs. In Trial 2, liver and intestinal weights, as well as in vitro oxygen consumption by liver slices, were decreased with nutrient restrictions. The reductions persisted after 2 wk of realimentation, yet no compensatory growth was observed. Feed intakes were increased gradually during the first 2 wk of realimentation. Composition of gain during the realimentation period was similar to that of unrestricted lambs. In Trial 3, neither gain nor feed efficiency during realimentation was enhanced as a result of previous nutrient deficiencies. Absence of compensatory growth in Trial 3 is possibly attributable to differences in gastrointestinal fill. Lambs subjected to short-term PR and ER seem to have similar recuperative capacity. PMID- 1894574 TI - Effect of different volatile fatty acids mixtures on energy metabolism in cattle. AB - Four Friesian steers (mean BW = 282 kg) were given mixtures of VFA and casein by intragastric infusion to give a total energy input of 675 kJ/kg BW.75. Casein supplied 16.3% of the energy and 777 mg N/kg BW.75. The molar proportion of butyric acid was held constant at 8 mol/100 mol, and the acetic and propionic acids varied inversely. Acetic acid was varied in 12 increments from 11 to 91 mol/100 mol and propionic acid proportion varied inversely. Heat production, blood (urea, insulin, beta-hydroxybutyrate, free fatty acids) and urine metabolites (urea, N, VFA) were measured. There were no differences (P greater than .05) in heat production until the acetic acid proportions exceeded approximately 90 mol/100 mol, at which point there was a decrease in heat production (P less than .05) accompanied by a considerable excretion of acetic acid in the urine. Above 80 mol/100 mol acetic acid, beta-hydroxybutyrate was greatly elevated, accompanied by a small decrease in blood glucose and blood insulin together with an increase in blood free fatty acid concentration. There was also an elevation of N excretion in the urine. When the proportion of propionic acid exceeded 76 mol/100 mol there were some metabolic disturbances resulting in blood hemolysis, an increase in N excretion in the urine, and nervous disposition of the animals. It is concluded that differences in heat production between roughage and concentrate diets are not likely to be a result of differences in the energetic response to different proportions of VFA. Differences in activity during standing, feeding, and ruminating may, therefore, be more important.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1894575 TI - Lupin as a protein supplement for growing lambs. AB - Whole lupins (Lupinus albus) were roasted with exit temperatures ranging from approximately 130 (moderate heat) to 175 degrees C (high heat). In situ N disappearance after 12 h of incubation in the rumen was 83% for raw lupins, 45% for lupins roasted at moderate temperatures, and 39% for lupins roasted at high temperatures. Lambs fed lupins roasted at moderate temperatures retained more N (P less than .01) than those fed soybean meal (SBM). However, growth rate and feed efficiency were similar among lambs fed diets containing SBM, raw lupins, or roasted lupins. Dehulled lupins commercially roasted at low, moderate, and high temperatures resulted in ruminal in situ N disappearances of 59, 47, and 43% for the respective temperatures. Dehulled lupins (Lupinus albus) were also roasted in a laboratory oven for 2, 4, and 6 h at 120, 140, and 160 degrees C. Simulation of roasting for 2 h had no effect (P greater than .10) on ruminal in situ N disappearance at any of the temperatures. In situ N disappearance was reduced (P less than .05) after roasting for 4 h at 160 degrees C, but acid detergent insoluble N was only moderately increased. Nitrogen retention in lambs fed raw, dehulled lupins was equal (P greater than .10) to that of lambs fed SBM. Whole lupins or dehulled lupins can replace SBM as the sole protein supplement for growing lambs. Although roasting lupins decreased ruminal in situ N disappearance, it had no effect on growth of lambs. PMID- 1894576 TI - Evaluation of dairy food processing wash water solids as a protein source: II. Microbial protein synthesis, duodenal nitrogen flow, and small intestinal amino acid disappearance. AB - Twelve ruminally, duodenally, and ileally-cannulated Hereford heifers (average initial BW 313 +/- 20 kg) were used in a replicated experiment to evaluate dairy food processing wash water solids (WWS) as a protein source. Heifers were fed 2.8 kg of chopped (7.6 cm) hay and one of three supplements (1.5 kg/d, DM basis). Supplements were formulated to be similar in energy and contained 1.0 (control), 23.2 (WWS), and 21.6% (soybean meal; SBM) CP on an OM basis. Total N and nonammonia N entering the duodenum (g/d) were greater (P less than .10) for heifers fed WWS and SBM supplements than for controls. Bacterial N flow (g/d) at the duodenum was less (P less than .10) for controls (43.9) than for WWS- (63.9) and SBM- (69.9) supplemented heifers. Feed escape N (g/d) was greater (P less than .10) for WWS-fed heifers than for those fed SBM (32.1 vs 20.7 g/d, respectively). Total tract N digestion (g/d) was greatest (P less than .10) for SBM, intermediate for WWS, and least for control heifers. Microbial protein synthesis (g/kg of OM intake) was enhanced (P less than .10) by WWS and SBM supplementation, but efficiency of synthesis (g/kg of OM fermented) did not differ among treatments. Essential amino acid (AA) disappearance in the small intestine (g/d) was less (P less than .10) for control than for the other two treatments. Nonessential AA disappearance was greatest (P less than .10) for the WWS and least (P less than .10) for the control treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1894577 TI - Evaluation of dairy food processing wash water solids as a protein source: III. Nitrogen utilization by heifers fed medium-concentrate diets. AB - Eight multicannulated heifers (average BW 415 +/- 34 kg) were used in a replicated 4 x 4 Latin square to evaluate fluid milk processing wash water solids (WWS) as a dietary N source. Heifers were fed corn/cottonseed hull-based diets containing soybean meal (control, 0% WWS N) or WWS replacing soybean meal at 33, 67, or 100% of supplemental dietary N. Total tract and ruminal DM and OM digestibilities decreased linearly or cubically (P less than .05) as dietary WWS N increased. Total ruminal VFA concentration (P less than .05) and propionic acid molar proportion (P less than .10) were greater in heifers fed 0 vs 100% WWS N. Heifers fed 0% WWS N had the greatest (P less than .05) ruminal ammonia concentration at all sampling times. Dietary WWS did not affect (P greater than .10) ruminal pH, fluid dilution rate, fluid flow, fluid volume, or turnover time. Total tract N digestibility decreased quadratically (P less than .10) with increasing WWS N in the diet. Supplemental WWS N did not affect (P greater than .10) flow of duodenal ammonia N or bacterial N, or efficiency of microbial N synthesis. Diets containing WWS N resulted in a cubic increase (P less than .10) in duodenal flow of essential amino acids compared with 0% WWS N; however, there were no differences in small intestinal amino acid disappearance. Data indicate that WWS can replace 33% of the soybean meal N in a corn/cottonseed hull-based diet without decreasing ruminal fermentation, fluid digesta kinetics, microbial efficiency, or small intestinal amino acid utilization. PMID- 1894579 TI - Tuberculosis and the acquired immune deficiency syndrome. PMID- 1894578 TI - Effects of feed intake on particle distribution, passage of digesta, and extent of digestion in the gastrointestinal tract of cattle. AB - Four nonlactating Holstein dairy cows (means +/- SD BW = 692 +/- 49 kg) were used in a 4 x 4 Latin square design experiment to determine changes in distribution of particles within the ruminoreticulum (RR) and total digestive tract in cattle fed a forage-based diet at four intake levels. Relationships between chewing activities and rates of particle breakdown, passage, and digestion were also determined. Percentage of large particles increased linearly in the dorsal rumen (P = .001), ventral rumen (P = .004), reticulum (P = .007), duodenum (P = .007), and feces (P = .006) as DMI increased. Particles of sizes less than or equal to 2,000 microns, eligible to pass from the RR, constituted 60 to 92% of particle DM in the RR. Increased feed intake resulted in a longer (P = .003) eating but a shorter (P = .008) ruminating time per kilogram of DM intake, whereas total chewing time per kilogram of DMI was not affected (P = .12). Passage rate constants of NDF from the RR increased (P = .03) with intake. There was no change (P = .87) in the rate constant for particle breakdown in the dorsal rumen with increased intake. Neither fractional passage rate of NDF nor the rate constant for particle breakdown was related to time spent eating (P + .12; P = .34) or time spent ruminating (P = .11; P = .55). It was concluded that rate of passage of small particles from the RR was a determinant of passage from the RR and that changes in rates of passage and breakdown of particles could only be partially explained by changes in chewing activities. PMID- 1894581 TI - A brief history of heat and chemical preservation and disinfection. PMID- 1894580 TI - Modelling the effect of pH, acidulant and temperature on the growth rate of Yersinia enterocolitica. AB - Growth of two pathogenic and one environmental serotype of Yersinia enterocolitica under acidic conditions and at 4 and 25 degrees C was investigated. At both temperatures the maximum growth inhibitory pH depended on the acidulant used and was in the order acetic greater than lactic greater than citric greater than sulphuric. At the lower temperature the maximum growth inhibitory pH was 0.3-0.5 pH units higher than at 25 degrees C. No difference was observed between the behaviour of pathogenic and environmental serotypes in this respect. Measurement of growth at a number of sub-optimal temperatures and pH values showed that the variation of growth rate with temperature could be represented by a square root plot. The effect of different pH values could be incorporated into the model by replacing the regression coefficient b by its relationship with pH. Values of maximum growth inhibitory pH derived from the model were in good agreement with experimental values with the exception of acetic acid. PMID- 1894582 TI - Interleukin-2: basic biology and therapeutic use. PMID- 1894583 TI - Different patterns of chromosome and molecular breakage in classic Ph1 chronic myelogenous leukemia (CML) and variant Ph1 CML. AB - Variant translocations involving either chromosome 9, chromosome 22, or both with other chromosomes have been reported in about 8% of chronic myelogenous leukemia (CML) patients. In the 22 Ph+ patients studied in our laboratory, two showed variant translocations: t(9;22;11) (q34;q11;q13), and t(9;11) (q34;q11). We compared the pattern of involvement of different chromosomes (and bands) in secondary structural changes in CMLs carrying the t(9;22) (q34;q11) and in the variant translocations. Analysis showed significant differences in the pattern of involvement of different chromosomes and chromosome sites in the secondary structural changes in classic CMLs. This study, thus identifies nonrandomly involved chromosome sites that may be targeted for detailed molecular analysis to obtain an understanding of their role in disease progression. In the variant translocations chromosomes and chromosome bands were nonrandomly involved. Breakpoint cluster region (bcr) of the BCR gene was found to be rearranged in our two cases. We compared the location of molecular breaks within the bcr in classic and variant translocations. We found that translocation breaks occurred more frequently in the 5' region, and less frequently in the 3' region of bcr in variant translocations as compared with classic translocations. The significance of these findings in the etiology of CML is discussed. PMID- 1894584 TI - Megakaryocytopoiesis in idiopathic thrombocytopenic purpura: a morphometric and immunohistochemical study on bone marrow biopsies with special emphasis on precursor cells. AB - A morphometric and immunohistochemical study was performed on trephine biopsies of the bone marrow in patients showing idiopathic thrombocytopenic purpura (ITP) and reactive thrombocytosis (RTH). Features of megakaryocytopoiesis were determined not only by using the periodic acid Schiff reaction (PAS), but also by immunostaining with the monoclonal antibody Y2/51, detecting a formalin-resistant epitope of glycoprotein IIIa (CD61). An increased number of megakaryocytes was observed in both ITP and in RTH as compared with a control group. Immunostaining revealed a predominance of small immature elements of this cell lineage, particularly in cases of ITP. Following previous experimental cell culture studies on megakaryocyte precursors and features derived from corresponding smear preparations, we characterized promegakaryoblasts immunomorphometrically. According to these calculations, ITP, as opposed to RTH, features a disproportionate expansion of the megakaryocyte precursor pool. PMID- 1894585 TI - Interferon therapy for agnogenic myeloid metaplasia complicated by immune hemolytic anemia. AB - A 69-year-old man with agnogenic myeloid metaplasia was treated with interferon alpha 2 as part of a Phase II clinical trial. The patient responded to this treatment with a definite improvement in bone marrow histology, demonstrating increased numbers of hematopoietic colonies and partial resorption of the myelofibrosis. Chromosomal analysis on 20 cells suggested the re-emergence of normal hematopoietic progenitor cells: whereas previously, all metaphase spreads demonstrated a deletion in chromosome 20, the patient was now chimeric, with two of 20 cells exhibiting a normal karyotype. Nevertheless, the patient's anemia progressed during interferon therapy, with the development of an immunologically mediated hemolytic disorder. This hemolytic process developed after prolonged treatment with interferon, accelerated during therapy, and resolved following splenectomy and withdrawal of the drug. Initially, screening tests failed to detect the presence of the autoantibody. Similar immunologic processes may have been overlooked in other patients treated with interferon, especially if tests for autoantibodies were obtained early in their course of treatment. This case suggests a therapeutic role for interferon-alpha 2 in the management of the myeloproliferative diseases. It is presented, too, to underscore the immunomodulatory potential of the biologic response modifiers and their capacity to induce immunologic disorders. PMID- 1894586 TI - Pseudo-Pelger-Huet anomaly after bone marrow transplantation. PMID- 1894587 TI - Valproate in combat-related posttraumatic stress disorder. AB - BACKGROUND: The symptoms of posttraumatic stress disorder (PTSD) suggest sympathetic nervous system hyperarousal and hyperreactivity. Pathophysiology of this condition may include stress-activated limbic kindling. Antikindling agents lithium and carbamazepine have been found effective for PTSD symptoms of intrusive reexperiencing and increased arousal. These facts suggest that valproate, another drug shown to interfere with limbic kindling, could also be effective for treatment of PTSD. METHOD: An open clinical trial of valproate was conducted in 16 Vietnam veterans diagnosed with DSM-III-R combat-related PTSD. RESULTS: Ten of 16 patients showed significant improvement, especially in hyperarousal/hyperreactivity symptoms. CONCLUSIONS: The efficacy of valproate in the treatment of PTSD should be rigorously studied. PMID- 1894588 TI - Paranoid schizophrenia in adolescence. AB - BACKGROUND: Paranoid schizophrenia is considered to be a rare condition in adolescence. Since this is contrary to the authors' clinical experience, they hypothesized that a controlled study would show that a significant number of adolescents would be diagnosed with paranoid schizophrenia and that scores from the childhood version of the Schedule for Affective Disorders and Schizophrenia (K-SADS) would differentiate between the paranoid schizophrenic adolescents and adolescents with other types of schizophrenia or with affective disorder. METHOD: The authors conducted a prospective study of 120 adolescents admitted consecutively to an adolescent psychiatric inpatient department. Patients were diagnosed on the basis of DSM-III after an 8-week period during which they were evaluated with a structured psychiatric history and psychiatric examination, the K-SADS, repeated nonstructured interviews, and extensive ward observations. RESULTS: Thirty-eight percent of the schizophrenic adolescents and 14% of the total hospitalized population met the DSM-III criteria for paranoid schizophrenia. The symptom profile of the paranoid schizophrenic adolescents clearly distinguished them from adolescents with other psychiatric disorders. CONCLUSIONS: Given the incidence of paranoid schizophrenia in an adolescent population, adolescent psychiatrists are likely to encounter this disorder. DSM III-R should be used in future studies to further clarify the issue of the prevalence of paranoid schizophrenia in adolescents. PMID- 1894589 TI - New-onset psychosis in HIV-infected patients. AB - BACKGROUND: Psychiatric symptoms and disorders are becoming increasingly evident in human immunodeficiency virus (HIV)-infected patients. As psychotic symptoms may be severe and require immediate behavioral management, the authors sought to determine the frequency and clinical characteristics of new-onset psychosis not obviously attributable to substance abuse or delirium in these patients. METHOD: The authors reviewed the English-language literature since 1981 by means of the Index Medicus and MEDLINE for reports of new-onset psychosis in HIV-infected patients and also examined the charts of 124 HIV-infected patients who had been followed up at the San Diego Veterans Affairs Medical Center since 1984. Cases of substance-induced psychosis and delirium were excluded. RESULTS: Results reflect a combination of cases from the authors' study and cases of new-onset HIV associated psychosis reported in the literature (N = 31). Results of the initial neurologic evaluation, including computed tomography (CT) scan and examination of the CSF, were normal in a majority of patients (CT = 12 of 23 patients; CSF = 10 of 14 patients). Psychotic symptoms improved with neuroleptic treatment although side effects were frequently seen. In some patients (N = 12) psychosis was the presenting manifestation of HIV infection or acquired immunodeficiency syndrome. A proportion of patients (N = 7 [23%]), especially those with an abnormal CT and EEG at the time of presentation with psychosis, tended to have a relatively rapid deterioration in cognitive and medical status. Differences between studies in population and method made it impossible to determine the frequency of new-onset psychosis in the general HIV-infected population. CONCLUSIONS: A common clinical feature noted in new-onset psychosis in HIV-infected patients was acute or subacute onset of symptoms, which included delusions, hallucinations, bizarre behavior, mood or affective disturbances, and mild memory or cognitive impairment. The etiological association of the HIV infection to the psychosis is yet to be established. PMID- 1894590 TI - Unexpected deaths in depressed medical inpatients treated with fluoxetine. AB - BACKGROUND: Depression in the medically ill is underdiagnosed and undertreated. Fluoxetine would appear promising in this population because of its efficacy and benign side effect profile, but it has not been systematically studied in the medically ill. METHOD: The authors report the cases of three seriously medically ill patients, seen in psychiatric consultation while patients on a general medical service, who were treated with fluoxetine for depression. Each was an elderly white female with pulmonary disease and atrial arrhythmias, including atrial fibrillation, and each was prescribed diuretics, nitrates, and other cardiac and/or pulmonary agents. RESULTS: Each patient died within 10 days of beginning fluoxetine treatment, from unexplained causes. CONCLUSIONS: The authors hypothesize that direct cardiac effects mediated by fluoxetine, or other factors, may have been contributory. The effects of fluoxetine on electrolytes, fluoxetine's possible effects on drug levels, and serotonin's effect on the pulmonary system are examined. Other antidepressant agents should be considered in this particular population until further data are available. PMID- 1894591 TI - Effects of placebo washout and dose in a comparison of sertraline and amitriptyline. PMID- 1894592 TI - Labetalol and ECT. PMID- 1894593 TI - Obsessional severity in Tourette's syndrome. PMID- 1894594 TI - Prescribing privileges for psychologists. PMID- 1894595 TI - Structural relationships and the classification of aminoacyl-tRNA synthetases. PMID- 1894596 TI - Identification of an amino acid-regulated mRNA from rat liver as the mammalian equivalent of bacterial ribosomal protein L22. AB - Amino acid deprivation of rat hepatoma cells induced the levels of a 612-base pair mRNA termed ASI (Shay, N. F., Nick, H. S., and Kilberg, M. S. (1990) J. Biol. Chem. 265, 17844-17848). The ASI mRNA was present at levels equal to or greater than actin in every rat tissue tested. The corresponding full-length cDNA was cloned, and the present report demonstrates that the deduced 184-residue amino acid sequence shares greater than 30% identity to a number of bacterial and chloroplast L22 ribosomal proteins, including those from Escherichia coli and Halobacterium halobium. A monospecific anti-peptide antibody was produced that upon immunochemical analysis of subcellular fractions of rat liver recognized a band in the microsomal fraction and, more specifically, reacted with a single polypeptide in the ribosomal large subunit fraction. The antibody did not react with any proteins of the mitochondrial large subunit, but did recognize a protein in human liver homogenate at the same relative mobility (23 kDa) as that observed for rat liver. PMID- 1894597 TI - Novel mechanism of intracellular calcium release in pituitary cells. AB - In sea urchin eggs an enzymatic metabolite of beta-NAD+, called cyclic ADP-ribose (cADPR), is as potent and powerful a releaser of sequestered intracellular Ca2+ as is inositol 1,4,5-trisphosphate (IP3). The enzyme that synthesizes cADPR is present in several vertebrate animal tissues, but the Ca(2+)-releasing activity of cADPR has not been described in mammalian cells. We report here that incubation of beta-NAD+ with cell-free extracts of several rat tissues (including pituitary gland) generates a product which releases intracellular Ca2+ stores in permeabilized rat pituitary GH4C1 cells. This product has the biological characteristics of cADPR (it acts after depletion of the IP3 stores and after blockade of the IP3 receptor by heparin). The response is mimicked, in a concentration-dependent manner, by authentic cADPR and is desensitized by prior incubation with cADPR. We conclude that cADPR is not only synthesized by certain mammalian cells but also acts in such cells to release compartmentalized intracellular Ca2+ by a mechanism that differs from that used by IP3. Therefore, cADPR may serve, in addition to IP3, as a second messenger for intracellular Ca2+ mobilization in mammalian cells. PMID- 1894598 TI - Carbonmonoxy dopamine beta-hydroxylase. Structural characterization by Fourier transform infrared, fluorescence, and x-ray absorption spectroscopy. AB - The carbon monoxide complex of ascorbate-reduced dopamine beta-hydroxylase has been prepared and characterized by Fourier transform infrared, fluorescence, and x-ray absorption spectroscopies. CO has previously been shown to be a competitive inhibitor with respect to O2, and binds to only one of the two copper atoms/active site (Blackburn, N. J., Pettingill, T. M., Seagraves, K. S., and Shigeta, R. T. (1990) J. Biol. Chem. 265, 15383-15386). Thus, it acts as an excellent probe of the O2-binding site. A single C-O infrared absorption band is observed at 2089 cm-1, shifting by 46 cm-1 to lower energy on substitution with either 13C16O or 12C18O. The 13C isotope shift is reversed to the position expected for 12CO upon vacuum flushing with 12CO gas, indicating that formation of the CO adduct is a fully reversible process. Binding of the substrate tyramine does not eliminate the infrared peak but causes a 3-cm-1 shift to lower energy. On the other hand, binding of a bifunctional inhibitor which cross-links the substrate and O2-binding site does eliminate the CO peak. These data, in conjunction with the competitive nature of CO binding with respect to O2, identify the CO-binding site as the O2-binding site, and place it in close proximity to the substrate-binding site. CO-dopamine beta-hydroxylase exhibits no luminescence in the visible region, suggesting a structure different from carbonmonoxy hemocyanin, and in all probability mononuclear. Analysis of extended x-ray absorption spectroscopy data is most consistent with an average coordination per Cu of 2-3 histidines, 0.5 CO, and 0.5 S atoms as ligands, and absorption edge comparisons indicates pseudo-4 coordination as the most likely geometry at each Cu(I) center. The results can be interpreted by a model involving inequivalent 4-coordination at each Cu(I) center in the CO adduct with CuAHis3S...CuBHis2CO-X as the coordination most consistent with all of the data. PMID- 1894599 TI - The membrane-bound bifunctional peptidylglycine alpha-amidating monooxygenase protein. Exploration of its domain structure through limited proteolysis. AB - The biosynthesis of alpha-amidated peptides from their glycine-extended precursors is catalyzed by the sequential action of peptidylglycine alpha hydroxylating monooxygenase (PHM) and peptidyl-alpha-hydroxyglycine alpha amidating lyase (PAL). The two enzymes are part of a bifunctional, integral membrane protein precursor, peptidylglycine alpha-amidating monooxygenase (PAM). The major forms of PAM mRNA in the adult rat atrium differ by the presence or absence of optional exon A, a 315-nucleotide segment separating the PHM and PAL domains. Using antipeptide antibodies specific to the PHM, exon A, PAL, and cytoplasmic domains of rat PAM, carbonate-washed atrial membranes were found to contain proteins corresponding to rPAM-1 and rPAM-2. Digestion of atrial membranes with a variety of endoproteinases released PHM and PAL catalytic activities. Dose-response curves indicated that both catalytic activities were extremely resistant to inactivation by trypsin. Endoproteolytic digestion of atrial membranes with trypsin, chymotrypsin, elastase, thermolysin, or endoproteinase Lys-C generated a 35-kDa PHM fragment. Digestion with trypsin, elastase, thermolysin, or endoproteinase Lys-C generated a 42-kDa PAL fragment. In contrast to the stability exhibited by the PHM and PAL domains, the cytoplasmic domain of PAM was destroyed by most of the enzymes; only digestion with endoproteinase Lys-C generated a stable fragment. Digestion with endoproteinase Arg-C removed the carboxyl-terminal tail from PAM but failed to release the PHM or PAL domains from the membranes. The PHM fragments generated by some of the endoproteinases showed a tendency to adhere to the membranes. Thus the bifunctional PAM protein consists of independent catalytic domains separated from each other and from the putative transmembrane domain by flexible regions accessible to attack by a wide variety of endoproteinases. PMID- 1894600 TI - Transcriptional regulation of the chicken CYP2H1 gene. Localization of a phenobarbital-responsive enhancer domain. AB - The mechanism by which the drugs phenobarbital and 2-allyl-2-isopropylacetamide induce levels of chicken cytochrome P-450 (CYP) mRNAs has been investigated in primary hepatocyte cultures from 17-day-old chick embryos. It has been demonstrated that three CYP mRNAs of 3.5, 2.5, and 2.2 kilobases (kb) are strongly induced by phenobarbital in primary hepatocytes, as found previously in chick embryo liver in ovo (Hansen, A. J., Elferink, L. A., and May, B. K. (1989) DNA (NY) 8, 179-191), and that, at least for the 3.5-kb mRNA, this is predominantly a result of enhanced transcription of the corresponding gene, CYP2H1. Transient transfection assays were carried out in primary cultures using constructs containing different lengths of CYP2H1 gene 5'-flanking sequence fused to the reporter chloramphenicol acetyl-transferase (CAT) gene. These experiments established that cis-acting elements located in the first 0.5 kb of the CYP2H1 gene 5'-flanking region direct high basal expression of the CAT gene, but do not mediate phenobarbital inducibility. When constructs containing more than 1.1 kb of CYP2H1 gene 5'-flanking sequence were examined, phenobarbital induction of CAT expression was observed, and a drug-responsive domain between positions -5.9 and 1.1 kb was identified. This domain has the properties of an enhancer, since it is able to confer phenobarbital responsiveness to the enhancerless SV40 promoter when tested in either orientation or at different distances from the promoter. The enhancer domain also responds to 2-allyl-2-isopropylacetamide, but whether the action of the two drugs is mediated by a single nuclear receptor interacting with common DNA elements in the domain remains to be established. PMID- 1894601 TI - Lipoproteins activate acyl-coenzyme A:cholesterol acyltransferase in macrophages only after cellular cholesterol pools are expanded to a critical threshold level. AB - Activation of acyl-CoA:cholesterol actyltransferase (ACAT) in macrophages by lipoproteins is a key event in atheroma foam cell formation. To help elucidate the mechanisms whereby lipoproteins stimulate ACAT, the early cellular events of lipoprotein-induced ACAT stimulation were studied in mouse peritoneal macrophages. As a function of increasing lipoprotein-cholesterol influx to the cell during the first few hours of incubation, ACAT activity was markedly stimulated by beta-very low density lipoprotein (beta-VLDL) and acetyl-low density lipoprotein (acetyl-LDL) only after lipoprotein-cholesterol influx reached a threshold level of approximately 25% above the basal cell cholesterol content. In contrast, LDL stimulated ACAT only minimally at this level of lipoprotein-cholesterol influx. In further experiments, the source of ACAT cholesterol substrate during the initial stimulation of ACAT was shown to be a mixture of cellular (approximately 75%) and lipoprotein-cholesterol (approximately 25%) in proportions that approximated the proportions of originally cellular and lipoprotein-cholesterol in the cell. Thus, lipoprotein cholesterol rapidly mixed with most or all of cellular cholesterol before ACAT esterification. Additional studies showed that LDL caused significant efflux of cellular cholesterol, thus providing at least a partial explanation for the relatively weak ACAT stimulatory potential of LDL. To support this idea, LDL that was modified to decrease its ability to induce net cellular cholesterol efflux stimulated ACAT 2-fold greater than control LDL when matched for lysosomal LDL cholesterol influx. Moreover, when the effective efflux potentials of beta-VLDL and acetyl-LDL were increased, ACAT stimulation was markedly decreased despite unchanged lipoprotein-cholesterol influx. Thus, macrophage ACAT is stimulated not directly by the influx of newly hydrolyzed lipoprotein-cholesterol but rather by net expansion of cellular cholesterol pools to a particular threshold level. This scheme has potentially important implications regarding the cellular and molecular mechanisms of foam cell formation. PMID- 1894603 TI - On the mechanism of the lycopene isomerase/cyclase reaction in Narcissus pseudonarcissus L. chromoplasts. AB - The lycopene cyclase reaction was investigated in Narcissus pseudonarcissus L. membranes using the terminal desaturation product of the system, 7,9,9',7'-tetra cis-lycopene (prolycopene) as substrate. The enzymatically formed bicyclic carotenes were trans configured, so the overall reaction consists of two individual processes, isomerization and cyclization. The two reactions were experimentally distinguished by use of the inhibitor [2-(p chlorophenylthio)triethylammonium chloride. NADPH, the essential cofactor for the overall reaction, originates from the plastid glycolytic pathway. It is shown that NADPH exhibits its function at the stage of isomerization and is also able to promote reduction of the prolycopene substrate in vitro. PMID- 1894602 TI - Aminolevulinic acid dehydratase in pea (Pisum sativum L.). Identification of an unusual metal-binding domain in the plant enzyme. AB - Aminolevulinic acid dehydratase (ALA dehydratase) catalyzes the second step of tetrapyrrole synthesis leading to the formation of heme and chlorophyll in higher plant cells. Antibodies elicited against spinach leaf ALA dehydratase were used to immunoscreen lambda gt11 cDNA libraries constructed from etiolated pea (Pisum sativum L.) leaf poly(A)+ RNAs. A set of overlapping cDNAs was characterized that encode the pea enzyme. The predicted amino acid sequence of the pea ALA dehydratase is similar to those reported for other eukaryotic and prokaryotic ALA dehydratases. The pea enzyme has an active site domain centered on lysine that is highly conserved in comparison to other known ALA dehydratases. Consistent with the previously reported requirement of Mg2+ for catalytic activity by plant ALA dehydratases, the pea enzyme lacks the characteristic Zn(2+)-binding domain present in other eukaryotic ALA dehydratases, but contains a distinctive metal ligand-binding domain based upon aspartate. Northern blot analyses demonstrated that ALA dehydratase mRNA is present in leaves, stems, and to a lesser extent in roots. Steady state levels of mRNA encoding ALA dehydratase exhibit little or no change during light-induced greening. PMID- 1894604 TI - Identification of an estrogen-responsive element in the rat LH beta gene. DNA estrogen receptor interactions and functional analysis. AB - Previous work from this laboratory demonstrated that 17-beta estradiol (E2) can directly stimulate the transcription rate of the rat luteinizing hormone beta (LH beta) gene and that an upstream portion of the LH beta gene between -2.0 and -0.6 kilobases could confer an E2-stimulated response to a reporter gene in transient expression assays. To localize the LH beta estrogen response element (ERE) by biological function, portions of the 5'-flanking region of the LH beta gene or synthetic oligonucleotides were inserted in expression vectors next to the herpes simplex virus thymidine kinase promoter fused to the chloramphenicol acetyltransferase gene. Constructs were transfected into GH3 cells, and transfected cells were treated for 48 h with E2. E2 stimulation of activity (2-4 fold) occurred with constructs containing the 15-base pair palindromic sequence (GGACACCATCTGTCC), found at bases -1173 to -1159 relative to the transcriptional start site in the LH beta gene. A construct containing a synthetic oligonucleotide of this putative LH beta ERE was stimulated 1.7-3-fold by E2, while a construct containing two copies of the sequence was stimulated to a slightly higher level (2.5-4.0-fold). An oligonucleotide in which the palindrome was mutated failed to confer E2 stimulation, and mutation of the palindromic region within the upstream region of the LH beta gene also eliminated the E2 response. The anti-estrogen tamoxifen could not elicit a response, nor could dehydrotestosterone or dexamethasone; however, thyroid hormone treatment resulted in a 2-2.5-fold stimulation. The 15-base pair LH beta gene palindrome was found to bind estrogen receptor (ER) complex directly by gel retardation experiments. Labeled LH beta ERE DNA formed three complexes with proteins from immature rat uterine extract. Two of these were associated with ER complexes, as determined by the comigration of [3H] estradiol bound to ER with these complexes, and by the ability of anti-ER antibody to associate with these complexes. The affinity of the LH beta ERE for ER was calculated by Scatchard analysis to be 2.2-5.0 nM, an approximately 5-10-fold lower affinity than for the ERE in the vitellogenin A2 gene region. The mutated ERE, which had no biological activity, could not compete effectively for binding to ER. ER which was heat-transformed at 30 degrees C had a similar affinity (2-5 nM) for the ERE as ER occupied with E2 (2-4 nM), while ER occupied by estrone had a lower affinity (9 nM).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1894605 TI - Rapid metabolism of fatty acids covalently bound to myelin proteolipid protein. AB - Proteolipid protein (PLP), the major protein of central nervous system myelin, contains approximately 2 mol of covalently bound fatty acids. In this study, the in vivo turnover rate of the acyl chains bound to PLP was determined in 40-day old rats after a single intracranial injection of [3H]palmitic acid. The apparent half-life of total fatty acids bound to PLP was approximately 7 days. After correction for acyl chain interconversion, the half-life of palmitate bound to PLP was only 3 days. This turnover rate is much more rapid than that of the protein moiety calculated under the same experimental conditions (t1/2 = 1 month). Additional evidence for the dynamic metabolism of acyl groups was provided by experiments in brain tissue slices which showed that acylation of PLP occurs in adult animals as well as during active myelination. Acylation of endogenous PLP in purified myelin and its subfractions was also studied during rat brain development using either [3H]palmitoyl-CoA or [3H]palmitic acid plus ATP and CoA. Labeling of endogenous PLP with [3H]palmitoyl-CoA was observed as early as 10 days postnatal and continued at the same rate throughout development. When [3H]palmitic acid was used as precursor in the presence of both ATP and CoA, esterification of myelin PLP occurred rapidly in adult animals, indicating that both nonacylated PLP and acyl-CoA ligase are present in myelin. Finally, pulse chase experiments in a cell-free system showed that PLP-bound fatty acids turn over with a half-life shorter than 10 min. These observations are consistent with the concept that acylation of myelin PLP is a dynamic process involved mainly in myelin maintenance and function. PMID- 1894606 TI - Carboxyl terminus region modulates catalytic activity of recombinant maize aldolase. AB - Site-directed mutagenesis was utilized to study the functional role of the COOH terminal region in recombinant maize aldolase. A single mutation was created in each of the last nine amino acids of the COOH terminus and characterized kinetically. Point mutations in the COOH-terminal region were found to influence both the rate of fructose 1,6-bisphosphate and fructose 1-phosphate cleavage. Catalytic efficiency, kcat/Km, was not affected by the mutations within experimental error consistent with this region of the COOH terminus modulating product release. Concentrations of the carbanion-enamine enzyme intermediate complex produced upon substrate cleavage increased with the severity of the point mutation. A condensation assay was developed to directly measure fructose 1,6 bisphosphate synthesized by aldolases in the presence of high triose phosphate concentrations. The maximal rate of aldol condensation of triose phosphates, D glyceralehyde-3-P and dihydroxyacetone-P, was affected by the point mutations to the same extent as the maximal rate of substrate cleavage. Interpretation of the data is consistent with point mutations in the COOH terminus predominantly affecting the proton exchange with the dihydroxyacetone-P enzymatic complex at the carbanion-enamine step and that this step is probably rate-limiting in the catalytic mechanism of recombinant maize aldolase. The role of the COOH-terminal region in aldolases is thus consistent with a sequence dependent modulation of catalytic activity. PMID- 1894607 TI - Monoclonal antibodies to ligand-occupied conformers of integrin alpha IIb beta 3 (glycoprotein IIb-IIIa) alter receptor affinity, specificity, and function. AB - Occupancy of integrin receptors induces conformational changes in the receptor, resulting in exposure of novel interactive sites termed ligand-induced binding sites (LIBS). We report here that Fab fragments of certain antibodies against LIBS on integrin alpha IIb beta 3 (platelet glycoprotein IIb-IIIa) block platelet aggregation. Thus, certain LIBS or the regions surrounding them may participate in events required for platelet aggregation. In addition, certain anti-alpha IIb beta 3 LIBS Fab fragments stimulated platelet aggregation. This was due to induction of fg binding to alpha IIb beta 3, apparently by shifting a conformational equilibrium between a "resting" and an "activated" state of alpha IIb beta 3. Some of the activating anti-LIBS Fab fragments also induced high affinity fibronectin binding to alpha IIb beta 3, whereas others did not. Thus, changes in the conformation of this integrin modulate both the specificity and affinity of ligand recognition. PMID- 1894608 TI - Polyene fatty acid interactions with recombinant intestinal and liver fatty acid binding proteins. Spectroscopic studies. AB - Binding and proximity relationships of fatty acids with recombinant rat liver fatty acid-binding protein (L-FABP) and intestinal fatty acid-binding protein (I FABP) were studied with absorption and fluorescence spectroscopy. Protein aromatic amino acids were examined in the absence and presence of bound fatty acid. Second derivative absorbance spectroscopy of the apo- and holoproteins suggested that fatty acid binding altered the conformation of L-FABP, but not of I-FABP. Fatty acid binding also blocked the accessibility of L-FABP tyrosine and I-FABP tryptophan to Stern-Volmer quenching by acrylamide, indicating that these amino acids were present in the fatty acid-binding pocket. Forster energy transfer from I-FABP tryptophan to bound cis-parinaric acid resulted in quenching of tryptophan lifetime and appearance of sensitized lifetime of bound cis parinaric acid. The calculated donor-acceptor distances were 16.9 +/- 0.6 and 19.2 +/- 0.3 A for I-FABP and L-FABP, respectively. Absorbance spectral shifts and ratios of fluorescence excitation maxima indicated that the parinaric acid microenvironment in the fatty acid-binding site of I-FABP was much less polar than that of L-FABP. Parinaric acids displayed similar rotational correlation time and limiting anisotropy when bound to I-FABP and to L-FABP. These results are consistent with a close proximity of bound fatty acids to the tyrosine and tryptophan residues and with immobilization of the polyene fatty acids in the fatty acid-binding site(s) of L-FABP and I-FABP. The two proteins differ in that only L-FABP has two fatty acid-binding sites and appears to undergo significant conformational change upon fatty acid binding. PMID- 1894609 TI - Characterization of a sulfotransferase responsible for the 4-O-sulfation of terminal beta-N-acetyl-D-galactosamine on asparagine-linked oligosaccharides of glycoprotein hormones. AB - The Asn-linked oligosaccharides on the glycoprotein hormones lutropin (LH) and thyrotropin terminate with the sequence SO4-4GalNAc beta 1-4GlcNAc beta 1-2 Man alpha-. Using a chemically synthesized trisaccharide GalNAc beta 1-4GlcNAc beta 1 2Man alpha 1-O(CH2)8COOCH3 (GGnM-MCO), we have developed a sensitive assay for the sulfotransferase responsible for the 4-O-sulfation of the terminal beta-D GalNAc. GGnM-MCO is incubated with a bovine pituitary membrane extract and [35S]3'-phosphoadenosine 5'-phosphosulfate ([35S]PAPS). The sulfated product [35S]SGGnM-MCO is separated from [35S]PAPS, PAPS degradation products and endogenous sulfated products by a two-step procedure utilizing an Ecteola cellulose column and a Sep-Pak (C18) cartridge. Characterization of the [35S]SGGnM-MCO produced in the assay indicates that sulfate is incorporated exclusively on the 4-position of GalNAc. Linear incorporation of sulfate into GGnM-MCO can be maintained for greater than 10 h. GGnM-4-sulfotransferase has a pH optimum of 7.2, requires the presence of a reducing agent, and is stimulated by, but does not require, divalent cations. Initial velocity studies indicate an apparent Km (Henri-Michaelis-Menten equilibrium constant) for PAPS of 4 microM and for GGnM-MCO of 9 microM. Incorporation of sulfate into the trisaccharide is stimulated 3-fold by the presence of basic proteins including deglycosylated LH. The stimulation by deglycosylated LH suggests that the protein component of glycoproteins that bear oligosaccharides terminating with GalNAc-GlcNAc-Man- may modulate GGnM-4-sulfotransferase. PMID- 1894610 TI - Chloroplast biogenesis. Detection of monovinyl protochlorophyll(ide) b in plants. AB - The occurrence of protochlorophyllide b and protochlorophyllide b phytyl ester in green plants is described. The chemical structure of protochlorophyllide b phytyl ester was established by proton nuclear magnetic resonance, fast atom bombardment mass spectroscopic analysis, and chemical derivatization coupled to electronic spectroscopic analysis. The macrocycles of protochlorophyll(ide) b are identical to those of conventional protochlorophyll(ide) except for the presence of a formyl group instead of a methyl group at position 3 of the macrocycles. They differ from chlorophyll(ide) b by the presence of an oxidized double bond at positions 7 and 8 of the macrocycles. The trivial name protochlorophyll(ide) b is proposed to differentiate these two tetrapyrroles from conventional protochlorophyll(ide), which in turn will be referred to as protochlorophyll(ide) a. Protochlorophyll(ide) b appears to be widely distributed in green plants. Its molar extinction coefficients in 80% acetone and diethyl ether are reported. The impact of this discovery on the heterogeneity of the chlorophyll a and b biosynthetic pathways is discussed. PMID- 1894611 TI - Cloning of the gene and cDNA for human heart chymase. AB - We have recently identified and characterized a chymotrypsin-like serine proteinase in human heart (human heart chymase) that is the most catalytically efficient enzyme described, thus far, for the cleavage of angiotensin I to yield angiotensin II and the dipeptide His-Leu. Compared to other chymases, this enzyme also has an unusually high degree of specificity for the substrate angiotensin I. We report here the molecular cloning and nucleotide sequence of the gene and cDNA encoding human heart chymase, and determination of its entire deduced amino acid sequence. These data indicate that human heart chymase is highly homologous to other members of the chymase subfamily of chymotrypsin-like proteinases and, most likely, all evolved from a common ancestral gene. Potential regulatory elements found in the 5'-untranslated region of other chymases are also found in the human heart chymase gene. However, this gene lacks mast cell-specific sequences found in the 5'- and 3'-untranslated regions of the rat chymase II gene. In addition, human heart chymase contains clusters of unique amino acid sequences located at key positions likely involved in substrate binding, which may contribute to its high substrate specificity. These contrasting features of the human heart chymase gene and cDNA, and the potential determinants of its primary structure that underlie its unique functional characteristics are considered. PMID- 1894613 TI - Staphylococcus aureus alpha-toxin. Dual mechanism of binding to target cells. AB - Staphylococcal alpha-toxin was radiolabeled to high specific radioactivity (1,500 3,000 Ci/mmol) under retention of its hemolytic activity. Binding studies with susceptible rabbit erythrocytes and highly resistant human erythrocytes revealed that binding of alpha-toxin to target cells can occur via two different mechanisms. Binding of alpha-toxin to rabbit erythrocytes initially involves specific binding sites and occurs at low concentrations, with half-maximal binding at 1-2 nM. In contrast, toxin binding to human erythrocytes is absorptive and nonspecific, in this case, significant binding as well as hemolysis occur only at alpha-toxin concentrations exceeding 1 microM. Autoradiographic analyses of membrane-associated alpha-toxin from either cell species proved that hemolysis was inevitably associated with the formation of toxin hexamers. Our data indicate that the high susceptibility of certain target cells toward alpha-toxin is caused by the presence of specific binding sites. However, membrane damage of both susceptible and nonsusceptible target cells occurs via a common mechanism involving toxin oligomerization and pore formation. PMID- 1894612 TI - Selective binding of cholesterol by recombinant fatty acid binding proteins. AB - The sterol binding specificity of rat recombinant liver fatty acid binding protein (L-FABP) and intestinal fatty acid binding protein (I-FABP) was characterized with [3H]cholesterol and a fluorescent sterol analog dehydroergosterol. Ligand binding analysis, fluorescence spectroscopy, and activation of microsomal acyl-CoA:cholesterol acyltransferase activity showed that L-FABP-bound sterols. 1) Lipidex-1000 assay showed a dissociation constant Kd = 0.78 +/- 0.18 microM and stoichiometry of 0.47 +/- 0.16 mol/mol for [3H]cholesterol binding to L-PABP. 2) With [3H]cholesterol/phosphatidylcholine liposomes, the cholesterol binding parameters for L-FABP were Kd = 1.53 +/- 0.28 microM and stoichiometry 0.83 +/- 0.07 mol/mol. 3) L-FABP interaction with dehydroergosterol altered the fluorescence intensity and polarization of dehydroergosterol. Dehydroergosterol bound to L-FABP with Kd = 0.37 microM and a stoichiometry of 0.83 mol/mol. 4) Cholesterol and dehydroergosterol decreased L FABP tyrosine lifetime. Dehydroergosterol binding produced sensitized emission of bound dehydroergosterol with longer lifetime.5) L-FABP bound two cis-parinaric acid molecules/molecule of protein. Cholesterol displaced one of these bound cis parinaric acids. 6) L-FABP enhanced acyl-CoA:cholesterol acyltransferase in a concentration-dependent manner. In contrast, these assays indicated that I-FABP did not bind sterols. Thus, L-FABP appears able to bind 1 mol of cholesterol/mol of L-FABP, the L-FABP sterol binding site is equivalent to one of the two fatty acid binding sites, and L-FABP stimulates acyl-CoA:cholesterol acyltransferase by transfer of cholesterol. PMID- 1894614 TI - Fenton chemistry. Amino acid oxidation. AB - The oxidation of amino acids by Fenton reagent (H2O2 + Fe(II] leads mainly to the formation of NH+4, alpha-ketoacids, CO2, oximes, and aldehydes or carboxylic acids containing one less carbon atom. Oxidation is almost completely dependent on the presence of bicarbonate ion and is stimulated by iron chelators at levels which are substoichiometric with respect to the iron concentration but is inhibited at higher concentrations. The stimulatory effect of chelators is not due merely to solubilization of catalytically inactive polymeric forms of Fe(OH)3 nor to the conversion of Fe(II) to complexes incapable of scavenging hydroxyl radicals. The results suggest that an iron chelate and another as yet unidentified form of iron are both required for maximal rates of amino acid oxidation. The metal ion-catalyzed oxidation of amino acids is likely a "caged" process, since the oxidation is not inhibited by hydroxyl radical scavengers, and the relative rates of oxidation of various amino acids by the Fenton system as well as the distribution of products formed (especially products of aromatic amino acids) are significantly different from those reported for amino acid oxidation by ionizing radiation. Several iron-binding proteins, peptides, and hemoglobin degradation products can replace Fe(II) or Fe(III) in the bicarbonate dependent oxidation of amino acids. In view of their ability to sequester metal ions and their susceptibility to oxidation by H2O2 in the presence of physiological concentrations of bicarbonate, amino acids may serve an important role in antioxidant defense against tissue damage. PMID- 1894615 TI - Relief from alkaline load in two-cell stage mouse embryos by bicarbonate/chloride exchange. AB - Mouse embryos at the two-cell stage are able to recover from an alkaline load. We found that this recovery is mediated by sodium-independent bicarbonate/chloride exchange: intracellular pH (pHi) recovery from alkaline load is inhibited by the anion exchange inhibitor 4,4'-diisothiocyanostilbene disulfonic acid, lack of bicarbonate, or lack of chloride. The dependence of the pHi recovery on extracellular chloride concentration exhibits Michaelis-Menten kinetics. Furthermore, uptake of chloride is inhibited in a dose-dependent manner by extracellular bicarbonate. The Km for external chloride was found to be about 3 mM, with a Ki for external bicarbonate of about 2 mM. The exchanger is active above approximately pH 7.15. These results demonstrate that mouse embryos at the two-cell stage possess a sodium-independent bicarbonate/chloride exchange mechanism that is similar to that found in other mammalian cells. This bicarbonate/chloride exchanger appears to be the sole pHi-regulatory mechanism in the two-cell stage mouse embryo, since our previous results have shown that there are apparently no specific mechanisms active in these cells for relieving acid loads. PMID- 1894616 TI - Phospholipase D activation in a cell-free system from human neutrophils by phorbol 12-myristate 13-acetate and guanosine 5'-O-(3-thiotriphosphate). Activation is calcium dependent and requires protein factors in both the plasma membrane and cytosol. AB - Receptor-linked activation of phospholipase D has been demonstrated recently in a variety of intact cell types including granulocytes, but little is known about the enzyme, its cofactor requirements, and regulation. Using [3H]alkyllysophosphatidylcholine to prelable an endogenous phosphatidylcholine substrate pool in conjunction with transphosphatidylation using ethanol to generate labeled phosphatidylethanol, we demonstrated a novel phospholipase D activity in neutrophil subcellular fractions. Guanosine 5'-O-3-(thiotriphosphate) (GTP gamma S) and phorbol 12-myristate 13-acetate (PMA) activated both phosphatidic acid generation and transphosphatidylation. Activity using both activators required the presence of not only plasma membrane but also cytosol, and proteolytic and thermal inactivation demonstrated the requirement for protein factors in both fractions. Using both stimuli, activity increased with increasing cytosol concentration. Product formation was approximately linear for about 10 min with PMA and 30 min with GTP gamma S, and both activators resulted in the total hydrolysis of up to 10% of the labeled phosphatidylcholine. The activity using both activators showed similar broad neutral pH optima, and both required the presence of micromolar levels of calcium, which by itself failed to activate at concentrations up to 1 mM. At low micromolar concentrations of nucleotides, activation was specific for guanine nucleotides and showed a specificity of GTP gamma S greater than guanyl-5'-yl imidodiphosphate greater than GTP, with no effect of GDP and GMP or adenine nucleotides, consistent with the participation of a guanine nucleotide regulatory protein. PMA activation was dependent on the presence of ATP, in particular when dialyzed cytosol was used, and was inhibited by about 50% by staurosporine, supporting a role for protein kinase C. However, purified protein kinase C failed to substitute for cytosol, implicating an additional cytosolic factor(s) in this response. These results indicate that the granulocytic phospholipase D pathway is a complex system that is regulated by at least two activation pathways, each comprised of components in two subcellular compartments. PMID- 1894618 TI - Failure of the intracellular itinerary of beta very low density lipoproteins to augment cholesterol esterification in macrophages from Watanabe heritable hyperlipidemic rabbits. AB - beta very low density lipoproteins (beta-VLDL) interact with mouse peritoneal macrophages via specific receptors leading to pronounced stimulation of cholesterol esterification. The present study has defined an alternative pathway for the processing of beta-VLDL in alveolar macrophages from Watanabe heritable hyperlipidemic (WHHL) rabbits. Macrophages from either New Zealand (NZ) or WHHL rabbits degraded 125I-beta-VLDL to an equivalent extent. Degradation was competed to a similar extent in both cell types by either excess unlabeled beta-VLDL or low density lipoprotein, indicative of a specific receptor involvement. Accumulation of intracellular degradation products of beta-VLDL labeled with the residualizing label, dilactitol-125I-tyramine, was similar in both cell types demonstrating that degradation was not due to secreted proteolytic enzymes. beta VLDL promoted the incorporation of [3H]oleate into cholesteryl-[3H]oleate and increased the cellular mass of cholesterol in NZ macrophages. In contrast, beta VLDL did not augment cholesteryl-[3H]oleate deposition in WHHL macrophages. This lack of cholesterol esterification occurred despite equivalent acyl CoA:cholesterol acyltransferase activity in microsomal fractions of both cell types, and similar augmentations in cholesteryl-[3H]oleate during incubation with phospholipase C-treated LDL. Incubation of WHHL macrophages with beta-VLDL increased cellular cholesterol mass, although the response was attenuated compared to NZ cells. To determine whether these disparities in cholesterol esterification were related to the catabolic fate of beta-VLDL-derived cholesterol esters, [3H]cholesteryl oleate was exchanged into the core of beta VLDL and incubated with macrophages in medium containing [14C]oleate. NZ macrophages accumulated both [3H]cholesterol and [3H]cholesteryl-[14C]oleate after 5 h, indicating hydrolysis and re-esterification of cholesterol esters. In contrast, WHHL macrophages only accumulated [3H]cholesterol esters, suggesting uptake of cholesterol esters without subsequent hydrolysis. These data demonstrate that WHHL macrophages possess a pathway for the intracellular processing of beta-VLDL that permits internalization of the particle without stimulation of cholesterol esterification. PMID- 1894617 TI - Characterization of two cDNAs encoding folate-binding proteins from L1210 murine leukemia cells. Increased expression associated with a genomic rearrangement. AB - L1210 murine leukemic cells grown under conditions of continuous low folate concentrations acquire increased levels of a high affinity/low capacity folate binding protein (FBP). Using an oligonucleotide probe complementary to the human FBP, we have cloned and sequenced two murine FBP cDNAs isolated from a library constructed using a L1210 subline adapted for growth on low levels of 5 formyltetrahydrofolate. The encoding proteins, designated FBP1 and FBP2, have predicted Mr values of 29,415 and 28,821, respectively. These proteins share significant sequence identity with each other (70%) and with the deduced sequences of the human- and bovine-encoded FBPs (68-79%). Southern blot analysis of the low folate-adapted cell line revealed that, while neither of the two FBP encoding genes was amplified, the FBP1 genomic locus had undergone rearrangement. On Northern blot analysis, this rearrangement was reflected in the enhanced expression (greater than 100-fold) of a FBP1-specific transcript which was 200 nucleotides shorter than the corresponding L1210 parental transcript. The increased expression of this transcript coincided with the increased expression of a membrane protein (Mr = 38,000) which could be affinity-labeled with a N hydroxysuccinimide ester of [3H]folate. Accordingly, the FBP1 transcript appears to encode the high affinity/low capacity FBP. Compared to parental L1210 cells, expression of the FBP2-encoding transcript was unchanged in this cell line and, while the exact nature of the protein is unclear, FBP2 may represent a fetal form of the FBP. PMID- 1894619 TI - Transport of proteins into chloroplasts. Requirements for the efficient import of two lumenal oxygen-evolving complex proteins into isolated thylakoids. AB - The 33- and 23-kDa proteins of the photosynthetic oxygen-evolving complex are synthesized in the cytosol and targeted into the thylakoid lumen by bipartite presequences. In this report, we describe conditions for the efficient import of each of these proteins by isolated pea thylakoids. Import of the 33-kDa protein requires both light and stromal extract. The probable function of the stromal extract is to provide stromal processing peptidase to remove the first "envelope transit" signal of the presequence. Import of the 23-kDa protein is also driven by light, but stromal extract is not required for import; furthermore, efficient import is still observed if the precursor is modified to completely block cleavage by residual stromal processing peptidase activity. The intermediate form of the 23-kDa protein, which is generated by incubation of the precursor protein with stromal processing peptidase, is also efficiently imported. The results indicate that the thylakoidal protein transport system can import both the precursor and intermediate forms of the 23-kDa protein, but probably only the intermediate form of the 33-kDa protein. PMID- 1894620 TI - Differential inhibition of rat mast cell proteinase I and II by members of the alpha-1-proteinase inhibitor family of serine proteinase inhibitors. AB - Rat mast cell proteinase II (RMCP II) from mucosal mast cells was titrated into rat serum, and the resulting serine proteinase inhibitor (serpin)-enzyme complex was purified by affinity chromatography on anti-RMCP II-Sepharose 4B and by Mono Q anion-exchange. The purified complex was used to raise polyclonal antibodies which, after cross-absorption against RMCP II-Sepharose 4B, were specific for serpin and were used to affinity purify two rat serpin molecules (RSI and RSII) that inhibit RMCP II in rat serum. The kinetic constants characterizing the interaction between RMCP II and RSI and RSII are ka, 2.2 x 10(5) and 1.65 x 10(5) M-1 s-1, respectively; Ki, 3.6 x 10(-10) and 1.0 x 10(-9) M; and kd, 7.9 x 10(-5) and 1.65 x 10(-4) s-1. Amino-terminal sequence analysis indicated that RSI and RSII are distinct, differing at the amino-terminal residues, and are products of the rat Spi-1 locus. Rat mast cell proteinase I (RMCP I) from connective tissue mast cells cleaved both RSI and RSII and was not inhibited. PMID- 1894621 TI - Molecular cloning and characterization of a factor that binds the human glucocorticoid receptor gene and represses its expression. AB - The human DNA binding factor GRF-1, which associates with the promoter region of the glucocorticoid receptor gene (hGR gene), is a repressor of glucocorticoid receptor transcription. The GRF-1 cDNA was cloned using polyclonal antibodies against the purified protein. The deduced amino acid sequence from the cDNA sequences show the presence of three sequence motifs characteristic of a zinc finger and one motif suggestive of a leucine zipper in which 1 cysteine is found instead of all leucines. The GRF-1 expressed in COS-1 cells has a molecular weight of 95,000 and enhances the homologous down-regulation of wild-type hGR gene expression. Biochemical analysis suggests that GRF-1 interaction is sequence specific and that transcriptional efficacy of GRF-1 is regulated through its interaction with specific sequence motif, namely 5'-GAAGGAGGTAGCGAGAAAAGAAACTG GAGAAACTCGGT.GG-3'. The GRF-1 mRNA is 6.5 kilobases long in rat liver and human MCF-7 cells, and its level is regulated by glucocorticoids. PMID- 1894623 TI - Structure and bacterial receptor activity of a human salivary proline-rich glycoprotein. AB - Using an overlay technique, we previously showed that the Gram-negative periodontal pathogen Fusobacterium nucleatum binds to a glycoprotein of Mr 89,000 (Prakobphol, A., Murray, P., and Fischer, S.J. (1987) Anal. Biochem. 164, 5-11) in the parotid saliva of some individuals. We now show that deglycosylation of the purified glycoprotein results in loss of receptor activity. Amino acid analysis of the protein core showed predominantly proline, glycine, and glutamic acid/glutamine, a characteristic of proline-rich glycoproteins (PRG). The amino terminus contained repeating sequences of Ser-Gln-Gly-Pro-Pro-Pro-Arg-Pro-Gly-Lys Pro-Glu-Gly-Pro-Pro-Pro- Gln-Gly that had significant compositional and sequence homology to that encoded by exon 3 of the PRB3 gene. We analyzed the PRG oligosaccharides by a combination of mass spectrometry techniques and nuclear magnetic resonance spectroscopy. Twenty-seven highly fucosylated structures were identified. The most abundant was as follows (where Fuc is fucose). (formula; see text) To understand the structural basis of F. nucleatum binding, we screened glycolipids and neoglycolipids carrying carbohydrate structures related to those of the PRG for receptor activity; components with unsubstituted terminal lactosamine residues best supported adherence. Neoglycolipids constructed from PRG oligosaccharides were also receptors. Treatment with beta-galactosidase, but not alpha-fucosidase, abolished binding, suggesting that unsubstituted lactosamine units, including the 6-antenna of the major oligosaccharide, mediate F. nucleatum adherence. PMID- 1894622 TI - Meprin-A and -B. Cell surface endopeptidases of the mouse kidney. AB - The proteinase meprin-A is a disulfide-linked tetramer of 90-kDa glycoprotein subunits. It is expressed at high levels in kidney brush border membranes of random bred and certain inbred strains of mice. Some mouse strains (e.g. C3H/He) do not express meprin-A subunits, but do produce a similar but less well characterized metalloendopeptidase, meprin-B. In the present study, meprin-B was purified from C3H/He mouse kidneys to electrophoretic homogeneity, and the relationship between it and meprin-A was investigated. The papain-solubilized form of meprin-B was similar to meprin-A in amino acid composition, molecular mass, secondary, and quaternary structure. However, immunoblots indicated that the enzymes have some common and some distinct epitopes. Lectin blots indicated both enzymes have high mannose and/or complex biantennary oligosaccharides, but there are differences in the complex-type glycosylation. Peptide maps and sequencing of cyanogen-bromide fragments of the enzymes revealed some different amino acid sequences. Thermal inactivation studies indicated that meprin-B was much less stable than meprin-A; the half-life for inactivation at 58 degrees C for meprin-A was 50 min, whereas for meprin-B it was less than 3 min. Both enzymes hydrolyzed azocasein and insulin B chain, but limited proteolysis of the enzymes with trypsin activated meprin-B 5-20-fold, whereas meprin-A was activated 2-fold at most. Analysis of hydrolysis products of the oxidized insulin B chain revealed some common and some distinct sites of cleavage. Bradykinin was a good substrate for meprin-A, while it was not hydrolyzed by meprin-B. A synthetic peptide, YLVC(SO3-)GERG, derived from insulin B chain was hydrolyzed faster by meprin-B than meprin-A, and neither enzyme was activated by trypsin treatment against this substrate. Taken together, the data indicate that the two metalloendopeptidases have many similarities but are distinct enzymes. PMID- 1894624 TI - Polylysine increases the number of insulin binding sites in soluble insulin receptor preparations. AB - The effects of cationic polyamino acids on insulin binding to soluble insulin receptor preparations were studied. Incubation of partially or fully purified receptor preparations with polylysine (pLys) increased by several-fold the amount of [125I]insulin that remained associated with the receptor, as determined both by precipitation of receptor-insulin complexes by polyethylene glycol or by separation of the complexes from the free hormone by gel filtration. This elevation in the amount of bound insulin resulted from increased number of insulin binding sites, and could not be attributed to an increased affinity of the receptors to insulin. In fact, pLys reduced 2-3-fold the affinity of insulin binding to its receptor as determined by equilibrium binding studies, and by monitoring the rate of exchange of bound [125I]insulin with unlabeled hormone. pLys induced specific interactions between insulin and its native receptor since other basic compounds such as histone, spermidine, polymixin B, compound 48/80, lysine, and arginine failed to reproduce its effects. pLys did not interact with the free ligand, nor did it promote interactions between insulin and denatured receptor forms. Furthermore, pLys did not induce binding of insulin to other proteins present in the partially purified receptor preparations. The effects of pLys were time and dose-dependent and were proportional to the pLys chain length. The longer the chain, the greater was the effect. Enhanced insulin binding and receptor beta-subunit autophosphorylation (in the presence of insulin) exhibited a similar dependency on the chain length of pLys. pLys effects on insulin binding were associated with formation of large protein aggregates that remained trapped at the top of Sephacryl S-300 columns. These aggregates contained substantial amounts of receptor-insulin complexes. Our results suggest that pLys induces formation of receptor clusters that create de novo insulin binding sites among adjacent receptor tetramers. Alternatively, formation of receptor aggregates might facilitate insulin binding to a soluble receptor subfraction that otherwise fails to bind the hormone. PMID- 1894625 TI - Cuttlefish spermatid-specific protein T. Molecular characterization of two variants T1 and T2, putative precursors of sperm protamine variants Sp1 and Sp2. AB - In cuttlefish, as in selachians and mammals, spermiogenesis is characterized by the double nuclear protein transition histones----intermediate protein (protein T)----protamine (protein Sp). The cuttlefish protein T, which consists of two structural variants phosphorylated at different degrees, is the first invertebrate spermatid-specific protein to be fully characterized and sequenced. The primary structures of these two variants were established from sequence analysis and mass spectrometric data of the proteins and their fragments. T1 and T2 are two highly related proteins of 78 and 77 residues, respectively, which differ only by four conservative substitutions, two inversions Ser in equilibrium with Arg, and the deletion of 1 residue of arginine in variant T2. The asymmetrical distribution of the hydrophobic and basic residues determines two well defined domains: an amino-terminal domain (residues 1-21) devoid of arginine and aromatic residues and containing all the aliphatic hydrophobic residues and a highly basic carboxyl-terminal domain (residues 22-77 or 78) that contains 77% of arginine, all the tyrosine residues, and most of the phosphorylated serine residues present in the protein. The complete structural identity of the basic carboxyl-terminal domain of spermatidal proteins T1 and T2 with the protamine variants Sp1 and Sp2 isolated from cuttlefish spermatozoa strongly suggests that T1 and T2 could be precursors of Sp1 and Sp2, respectively. PMID- 1894627 TI - The kinetic behavior of xanthine oxidase containing chemically modified flavins. AB - The steady-state and rapid kinetic properties of xanthine oxidase containing a series of FAD analogs of varying reduction potential have been investigated. From steady-state analysis, Vmax is found to exhibit a sigmoidal dependence on the flavin midpoint potential in the homologous series. This dependence is accurately described by a model in which the rate of catalysis is attenuated by the amount of partially reduced enzyme generated during turnover possessing an unfavorable distribution of reducing equivalents among the several redox-active centers of the protein. The model assumes that reducing equivalents equilibrate among these centers rapidly compared to the limiting rates for the reductive and oxidative half-reactions. This assumption is borne out by a quantitative analysis of the reductive and oxidative half-reactions of the several enzyme forms investigated in detail. It is demonstrated in these studies that xanthine oxidase containing low potential flavin derivatives such as 1-deaza, 6-hydroxy, or 8-hydroxy FAD exhibits low turnover not because of inherently slow rates of reduction by xanthine or oxidation by molecular oxygen, but because in partially reduced enzyme generated in the course of turnover reducing equivalents are distributed within the enzyme in such a way that the enzyme can participate in neither the reductive nor oxidative half-reactions. These results provide confirmation of the operation of a thermodynamic control mechanism in a simple electron-transferring system. PMID- 1894626 TI - Chemical modification of the bovine pituitary multicatalytic proteinase complex by N-acetylimidazole. Reversible activation of casein hydrolysis. AB - The effect of N-acetylimidazole, a mild acetylating reagent, on the catalytic activities and subunit structure of the bovine pituitary multicatalytic proteinase complex (MPC) was studied. The trypsin-like activity (cleavage of Cbz D-Ala-Leu-Arg-2-naphthylamide) and the peptidylglutamyl-peptide bond hydrolyzing (PGP) activity (cleavage of Cbz-Leu-Leu-Glu-2-naphthylamide) of MPC were rapidly inactivated by N-acetylimidazole, whereas the chymotrypsin-like activity (cleavage of Cbz-Gly-Gly-Leu-p-nitroanilide) was inactivated slowly. However, the hydrolysis of casein was markedly stimulated. Hydrolysis of casein by the acetylated enzyme generated a stable intermediate (21 kDa) which could be further degraded by native MPC. Treatment of acetylated MPC with hydroxylamine reversed the changes in trypsin-like and caseinolytic activities but did not restore the PGP activity. N-Acetylimidazole did not dissociate MPC but altered its migration on nondissociating gels presumably by acetylation of epsilon-amino groups of lysine residues. Hydroxylamine did not alter the gel electrophoretic appearance of the acetylated enzyme. These results indicate that acetylation of thiol or tyrosyl groups changes the trypsin-like and caseinolytic activities, and that amino group acetylation inhibits the PGP activity. Degradation of casein by MPC appears to be a sequential process with initial cleavage catalyzed by a component distinct from the chymotrypsin-like, trypsin-like, and PGP activities. The latter three components likely participate in the secondary proteolysis of the generated intermediates. PMID- 1894628 TI - Expression of human pancreatic polypeptide in heterologous cell lines. AB - Pancreatic polypeptide (PP) is initially synthesized as a larger precursor that requires post-translational processing to produce the biologically active hexatriacontapeptide. These steps include tryptic cleavage at paired basic residues, their subsequent removal by a carboxypeptidase B-like enzyme, and formation of a carboxyl-terminal amide moiety via the action of peptidyl-glycyl alpha-amidating monooxygenase. To examine these reactions further, we utilized the pZIPneo(SVX) retroviral vector to express a cDNA clone encoding human PP in several cell lines including a fibroblast line (psi-2), two endocrine cell lines known to produce amidated peptides (AtT-20 and PC12), and two lines that do not ordinarily produce amidated peptides (RIN5-f and GH3). Transfected psi-2 cells produced an unprocessed precursor of PP that appeared to be secreted constitutively with little remaining in intracellular stores. No post translational processing of the PP precursor was evident in these cells. By contrast, all 4 endocrine-derived cell lines, regardless of the nature of their endogenous products, were capable of expressing fully processed and carboxyl terminally amidated PP. Moreover, these lines had the ability to store the processed products. Our results support the notion that post-translational processing of peptide hormone precursors requires storage in secretory granules that contain the appropriate processing enzymes. Furthermore, enzymes such as peptidyl-glycyl alpha-amidating monooxygenase that are required for processing peptides may be a common feature of endocrine-derived cells regardless of the requirement for their activity to process endogenous products. PMID- 1894630 TI - Inhibition of recA-mediated strand exchange by adducts of azacytosine-containing DNA and the EcoRII methylase. AB - Wild type Escherichia coli cells containing elevated levels of DNA (cytosine 5)methyltransferases have increased sensitivity to the toxic effects of 5 azacytidine. The methyltransferases form tight binding complexes with azacytosine in DNA which could interfere with the recA recBCD repair pathway which is largely responsible for cell survival after treatment with the drug. We therefore determined if these complexes interfered with recA-mediated strand exchange in vitro. 32P-Labeled DNA fragments containing a single EcoRII site, with cytosine in the (-) strand replaced by 5-azacytosine, were prepared. We investigated the effect of the EcoRII methyltransferase on recA-mediated strand exchange with homologous M13 DNA by electrophoresis in agarose gels. In the absence of the methylase the rate and extent of strand exchange of azacytosine-containing DNA is the same as control DNA. In the presence of the methyltransferase strand exchange is inhibited, but some incorporation of duplexes into recA-single-stranded DNA (ssDNA) complexes still occurs. The formation of these complexes is dependent on the length of the fragment 3' to the methylase binding site on the strand complementary to the ssDNA. The greater the length the greater the number of complexes that form. S-Adenosyl-L-methionine, which enhances binding of the methyltransferase to azacytosine-containing DNA, causes an increase in the inhibition of strand exchange and an increase in the number of inactive complexes formed. The complexes can be dissociated with guanidinium chloride which denatures the methyltransferase and leads to release of the (+) strand. The (-) strand remains associated with the ssDNA. This result implies that a plectonemic joint is formed between recA-ssDNA complexes and azacytosine-containing DNA methyltransferase complexes. However, branch migration in these complexes is inhibited. Denaturation of the methyltransferase allows branch migration to proceed to completion, releasing the (+) strand. PMID- 1894629 TI - Molecular cloning, induction and taxonomic distribution of caffeoyl-CoA 3-O methyltransferase, an enzyme involved in disease resistance. AB - Trans-Caffeoyl-CoA 3-O-methyltransferase is involved in the reinforcement of the plant cell wall under conditions that trigger the disease resistance response (Pakusch, A.-E., Kneusel, R.E., and Matern, U. (1989) Arch. Biochem. Biophys. 271, 488-494). Partial amino acid sequences of the enzyme from cultured parsley cells that had been treated with a crude elicitor were identified (Pakusch, A. E., Matern, U., and Schiltz, E. (1991) Plant Physiol. 95, 137-143), and corresponding degenerated oligonucleotides of 29- and 30-nucleotide length were synthesized. Northern hybridizations with these probes revealed one specific RNA band, and the amount of this RNA appeared to be transiently induced upon elicitation of the cells. De novo enzyme synthesis was confirmed by Western blotting experiments using a specific antiserum. The time course of induction closely followed the pattern observed for phenylalanine ammonia-lyase and suggested the operational coordination of the methyltransferase with the general phenylpropanoid pathway in vivo. Full size cDNA of 1.258 kilobases was isolated in lambda gt11, sequenced and found to contain a remarkably long 5'-untranslated leader sequence followed by an open reading frame that codes for a 241-residue polypeptide representing the 27-kDa subunit of the native, dimeric parsley enzyme. Almost no homology was found to protein sequences filed in data banks. Southern hybridization with genomic DNA suggested that only one or two copies of the respective gene(s) are present in the parsley genome. Caffeoyl-CoA-specific methyltransferase activity was demonstrated in taxonomically widely diverse plants such as Dianthus caryophyllus (Caryophyllaceae), Carthamus tinctorius (Asteraceae) or Daucus carota, and Ammi majus (Apiaceae) where it is commonly induced by elicitor treatment. In Northern blots with RNA from Ammi or Daucus, parsley cDNA hybridized specifically to one band comparable in size to the parsley RNA, whereas Dianthus and Carthamus appear to code for slightly larger RNAs (roughly 1.45 and 1.3 kilobases, respectively). Slot-blot hybridizations revealed in all instances the rapid and transient increase of mRNA levels in response to elicitation. This emphasizes the integral role of the enzyme in disease resistance expression in plants far beyond parsley and also illustrates a new physiological context for the induction of 4-coumarate:CoA ligase. PMID- 1894631 TI - Growth hormone action in rat insulinoma cells expressing truncated growth hormone receptors. AB - Transfection of the insulin-producing rat islet tumor cell line RIN-5AH with a full length cDNA of the rat hepatic growth hormone (GH) receptor (GH-R1-638) augments the GH-responsive insulin synthesis in these cells. Using this functional system we analyzed the effect of COOH-terminal truncation of the GH receptor. Two mutated cDNAs encoding truncated GH receptors, GH-R1-294 and GH-R1 454, respectively, were generated by site-directed mutagenesis and transfected into the RIN cells. Both receptor mutants were expressed on the cell surface and displayed normal GH binding affinity. Whereas GH-R1-638 had a molecular mass of about 110 kDa, GH-R1-294 and GH-R1-454 showed molecular masses of 49 and 80 kDa, respectively. Cells expressing GH-R1-454 internalized GH to a similar extent as cells transfected with the full length receptor and the parent cell line, but GH R1-294-expressing cells showed a markedly reduced capability of GH internalization. In contrast to cells transfected with GH-R1-638, none of the cell lines expressing truncated GH receptors exhibited any increase of the GH stimulated insulin production. We conclude that domains within the COOH-terminal half of the cytoplasmic part of the GH receptor are required for transduction of the signal for GH-stimulated insulin synthesis, whereas cytoplasmic domains proximal to the transmembrane region are involved in receptor-mediated GH internalization. PMID- 1894633 TI - Erythroleukemia differentiation. Distinctive responses of the erythroid-specific and the nonspecific delta-aminolevulinate synthase mRNA. AB - We have examined the levels of delta-aminolevulinate synthase (ALAS) mRNAs encoding the erythroid-specific (ALAS-E) and the nonspecific (ALAS-N) ALAS isozymes in murine Friend virus-transformed erythroleukemia (MEL) cells. Both ALAS-E and ALAS-N mRNAs were detected in a clone of dimethyl sulfoxide (Me2SO) sensitive MEL cells, termed DS-19, without cross-hybridization. Untreated DS-19 cells contained approximately 10-fold more ALAS-E mRNA than ALAS-N mRNA. When DS 19 cells were treated with Me2SO or hemin, ALAS-N mRNA declined rapidly, which was followed by a marked increase in ALAS-E mRNA. Similarly, the immunoquantifiable ALAS-N protein decreased, while the ALAS-E protein increased upon Me2SO treatment. A clone of Me2SO-resistant cells, termed DR-1, which fails to undergo erythroid differentiation, was found to lack ALAS-E mRNA, whereas it showed significant induction responses of mRNAs for other heme pathway enzymes by Me2SO treatment. DR-1 cells contained a similar level of an erythroid-specific transcription factor, GATA-1, as did DS-19 cells, and had neither major deletion nor rearrangement of the ALAS-E gene. These findings indicate that the genes encoding the two ALAS isozymes are under separate controls and suggest that ALAS E mRNA accumulation is responsible for increased heme synthesis in MEL cells undergoing erythroid differentiation. PMID- 1894632 TI - Entry of diphtheria toxin-protein A chimeras into cells. AB - Fusion proteins consisting of diphtheria toxin and a duplicated Fc-binding domain of protein A were made in vitro after amplification of the DNA template by the polymerase chain reaction. The fusion proteins bound avidly to Vero cells coated with antibodies. A fusion protein containing full-length diphtheria toxin was toxic at lower concentrations than diphtheria toxin alone, apparently due to more efficient binding. The enzymatic part of the fusion protein was translocated across the surface membrane upon exposure to low pH. Like authentic diphtheria toxin, the fusion protein formed cation selective channels at low pH. Excess amounts of unlabeled diphtheria toxin inhibited formation of pronase-protected fragments derived from radiolabeled fusion protein. Furthermore, conditions that down-regulate the diphtheria toxin receptors reduced the sensitivity of the cells to the fusion protein, supporting the notion that authentic diphtheria toxin receptors are required. At temperatures below 18 degrees C the toxicity of the fusion protein was strongly reduced, whereas there was no temperature block for authentic diphtheria toxin. Brefeldin A protected Vero cells against the fusion protein but not against diphtheria toxin. The results indicate that the diphtheria toxin receptor is required for efficient toxin translocation even under conditions where the toxin is bound by an alternate binding moiety, and they suggest that the intracellular routing of the fusion protein is different from that of diphtheria toxin. PMID- 1894634 TI - Adenylate cyclase toxin from Bordetella pertussis. Conformational change associated with toxin activity. AB - Adenylate cyclase (AC) toxin from Bordetella pertussis interacts with and enters eukaryotic cells to catalyze the production of supraphysiologic levels of cyclic AMP. Although the calmodulin-activated enzymatic activity (ability to convert ATP to cyclic AMP in a cell-free assay) of this molecule is calcium independent, its toxin activity (ability to increase cyclic AMP levels in intact target cells) requires extracellular calcium. Toxin activity as a function of calcium concentration is biphasic, with no intoxication occurring in the absence of calcium, low level intoxication (200-300 pmol of cyclic AMP/mg of Jurkat cell protein) occurring with free calcium concentrations between 100 nM and 100 microM and a 10-fold increase in AC toxin activity at free calcium concentrations above 300 microM. The molecule exhibits a conformational change when free calcium concentrations exceed 100 microM as demonstrated by shift in intrinsic tryptophan fluorescence, an alteration in binding of one anti-AC monoclonal antibody, protection of a fragment from trypsin-mediated proteolysis, and a structural modification as illustrated by electron microscopy. Thus, it appears that an increase in the ambient calcium concentration to a critical point and the ensuing interaction of the toxin with calcium induces a conformational change which is necessary for its insertion into the target cell and for delivery of its catalytic domain to the cell interior. PMID- 1894635 TI - The gene encoding the Act-2 cytokine. Genomic structure, HTLV-I/Tax responsiveness of 5' upstream sequences, and chromosomal localization. AB - Act-2 is a cytokine that belongs to a superfamily of structurally related proteins. Act-2 expression is rapidly induced in T cells, B cells, and monocytes upon mitogenic stimulation. The Act-2 genomic locus is on chromosome 17q. The exons and exon/intron splice junctions have been sequenced, as have the sequences upstream of exon 1. A classical TATA box is located immediately upstream of the transcription initiation site. The upstream sequences possess promoter activity and can be functionally activated after treatment of Jurkat T cells with phythohemagglutinin plus phorbol myristrate acetate. In addition, Act-2 promoter chloramphenicol acetyltransferase constructs are expressed in human T cell lymphotropic virus type I (HTLV-I)-infected MT-2 cells and in Jurkat cells which can be induced to express the transactivator gene (tax) product of HTLV-I. PMID- 1894636 TI - TIP 1, a cold shock-inducible gene of Saccharomyces cerevisiae. AB - Using differential hybridization, genes whose expression is induced at low temperatures were identified in yeast Saccharomyces cerevisiae. One of these genes that corresponds to an mRNA that is induced 6-8-fold within 2 h after shifting the culture temperature from 30 to 10 degrees C was further characterized. Surprisingly, its expression was also induced by heat shock, and thus the gene was designated TIP 1 (temperature shock-inducible protein gene). Southern hybridization analysis demonstrated that there are several genes homologous to the TIP 1 gene on the yeast genome. A TIP 1 disruption mutation exerted an observable effect neither on growth nor on viability after being exposed to freezing temperatures. The TIP 1 gene encodes a protein of 210 amino acid residues with a molecular weight of 20,727, containing 20.0% alanine and 23.3% serine. The TIP 1 protein has a typical signal peptide at the amino terminal end and an extremely hydrophobic sequence at the carboxyl-terminal end. The TIP 1 protein is thus likely to be secreted across the membrane and anchored on the outside surface of the plasma membrane. These results indicate that the TIP 1 protein is a new type of stress inducible protein in yeast. PMID- 1894637 TI - Structure of laminin variants. The 300-kDa chains of murine and bovine heart laminin are related to the human placenta merosin heavy chain and replace the a chain in some laminin variants. AB - A variant of laminin has previously been isolated from murine heart and shown to be distinct from laminin purified from a traditional source, the murine Engelbreth-Holm-Swarm (EHS) tumor (Paulsson, M., and Saladin, K. (1989) J. Biol. Chem. 264, 18726-18732). It contains a novel polypeptide chain designated as 300 kDa, which is not found in laminin from the EHS tumor. In the present study, heart laminin was purified from bovine tissue and shown to be structurally and immunochemically closely related to the murine protein. Further, heart laminins were compared with merosin, a laminin-like protein isolated from human placenta (Ehrig, K., Leivo, I., Argraves, W. S., Ruoslahti, E., and Engvall, E. (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 3264-3268). The 300-kDa chain of bovine heart laminin cross-reacted with the heavy chain of merosin, showing that these polypeptides are closely related, albeit from different species. Heart laminin is more resistant to proteolysis than laminin derived from the EHS tumor. A large fragment could be prepared by digestion with thermolysin, which consisted of an almost intact long arm structure and variably long, residual short arm structures. Analysis of its structure shows that the 300-kDa heavy chain is disulfide-bonded to the B1 and B2 chains in the center of the laminin cross and forms the long arm together with these chains. It thereby replaces the A chain, well known from tumor sources, in the laminin structure. PMID- 1894638 TI - Cell adhesion, spreading, and motility of GM3-expressing cells based on glycolipid-glycolipid interaction. AB - Cell lines expressing varying levels of ganglioside GM3 at the cell surface show different degrees of adhesion and spreading on solid phase coated with such glycosphingolipids (GSLs) as Gg3 (GalNAc beta 1----4Gal beta 1----4Glc beta 1--- 1Cer), LacCer (Gal beta 1----4Glc beta 1----1Cer), or Gb4 (GalNAc beta 1----3Gal alpha 1----4Gal beta 1----4Glc beta 1----1Cer) (where Cer is ceramide), which may have structures complementary to GM3, but not on solid phase coated with various other GSLs. The degree of cell adhesion and spreading on Gg3 was correlated with the degree of cell-surface GM3 expression, as defined by reactivity with anti-GM3 monoclonal antibody (mAb) DH2. Only cells with high GM3 expression adhered on solid phase coated with LacCer or Gb4. Adhesion of GM3-expressing cells on Gg3-, LacCer-, and Gb4-coated solid phase is based on interaction of GM3 with Gg3 and, to a lesser extent, with LacCer and Gb4, as demonstrated by: (i) the interaction of the GM3 liposome with solid phase coated with Gg3, LacCer, and Gb4, respectively; (ii) the abolition of cell adhesion on each GSL-coated solid phase by treatment of cells with mAb DH2 or sialidase; and (iii) the inhibition of cell adhesion by treatment of GSL-coated solid phase with mAb specific to each GSL. Sialosyllactosyl-lysyllysine conjugate was bound to Gg3 adsorbed on a C18 silica gel column in the presence of bivalent cation, suggesting that the carbohydrate moiety of GM3 is involved in GM3-Gg3 interaction. Not only the adhesion and spreading of GM3-expressing cells, but also their cell motility was greatly enhanced on Gg3-coated solid phase, as determined by Transwell assay and phagokinetic track assay on a gold sol-coated surface. Spreading and motility of GM3-expressing cells on Gg3-coated solid phase were both inhibited by treatment of cells with mAb DH2 or sialidase. These results provide evidence that not only cell adhesion, but also spreading and motility in these cell lines are controlled by complementary GSL-GSL interaction. PMID- 1894639 TI - A 58-kDa resident protein of the cis Golgi cisterna is not terminally glycosylated. AB - A 58-kDa Golgi protein (gp58) was previously identified and found to be concentrated in cis Golgi cisternae in several cell types (Saraste, J., Palade, G.E., and Farquhar, M.G. (1987) J. Cell Biol. 105, 2021-2029). In this study the protein was partially purified from rat pancreas and mouse myeloma cells in order to characterize its oligosaccharides. It migrated on sodium dodecyl sulfate polyacrylamide gels as a 57-58-kDa doublet under reducing conditions or as a single approximately 116-kDa band under nonreducing conditions. Pancreatic gp58 was susceptible to alpha-N-acetylgalactosaminidase digestion and it bound concanavalin A, Helix pomatia, Dolichos biflorus, soybean agglutinin, and Bauhinia purpurea lectins, but not Ricinus communis agglutinin or lectins from Griffonia simplicifolia-1, Arachis hypogaea, and Limulus polyphemus. It bound Ricinus communis agglutinin after galactosylation with GlcNAc galactosyltransferase. These data demonstrate that pancreatic p58 contains immature N-linked moieties with nonreducing terminal GlcNAc residues as well as the initiating GalNAc of O-linked glycoproteins. Myeloma gp58 was sensitive to endo-beta-N-acetylglucosaminidase H, and oligosaccharide analysis of its [3H]glucosamine-labeled glycopeptides indicated that it also contained immature N linked glycans. Some of the latter consist of high mannose chains (high affinity for concanavalin A, endo-beta-N-acetylglucosaminidase H-sensitive), but the predominant (95%) species are neutral tri- or tetraantennary N-linked chains containing GlcNAc (no binding to concanavalin A). Glycopeptides from biosynthetically labeled myeloma cells did not contain detectable base labile oligosaccharides, indicating that unlike pancreatic p58, myeloma gp58 may not be an O-linked glycoprotein. Neither pancreatic nor myeloma gp58 contained terminally processed oligosaccharides, indicating that gp58 has not been modified by trans-Golgi glycosyltransferases. Thus, the oligosaccharide content of gp58 is consistent with the assumption that this protein is retained in the cis Golgi cisternae during biosynthesis instead of being transported across the Golgi stacks and targeted back to the cis Golgi from the trans side. PMID- 1894640 TI - Endogenous modulators of glucocorticoid receptor function also regulate purified protein kinase C. AB - Modulator-1 and -2, proposed to be novel ether-linked aminophosphoglycerides, were originally identified as regulators of glucocorticoid receptor function (Bodine, P. V., and Litwack, G. (1990) J. Biol. Chem. 265, 9544-9554). We now demonstrate that these modulators are also potent new stimulators of protein kinase C activity in vitro. These endogenous biomolecules regulate purified protein kinase C activity in a biphasic and dose-dependent pattern, as determined by histone phosphorylation. Modulators, at concentrations within their apparent cellular range, stimulate protein kinase C-catalyzed histone phosphorylation 2-4 fold when added separately, or 10-12-fold when added together. This enhancement of kinase activity apparently is specific for protein kinase C, since neither protein kinase M, nor cAMP-dependent protein kinase A are stimulated by the modulators. The stimulation of purified protein kinase C occurs only when the enzyme has been initially activated by calcium, phosphatidylserine, and diacylglycerol, indicating that the modulators do not simply substitute for one of the enzyme cofactors. In addition, the modulators appear to interact directly with protein kinase C, perhaps with the regulatory domain of the enzyme, since these biomolecules inhibit the binding of phorbol ester to purified protein kinase C. Finally, time-course studies of protein kinase C-catalyzed histone phosphorylation indicate that the velocity of the enzyme reaction is increased by the modulators. Taken together, these results suggest that the modulators are a new class of regulators of protein kinase C. PMID- 1894642 TI - Expression of a neuronal Ca2+/calmodulin-dependent protein kinase, CaM kinase-Gr, in rat thymus. AB - The regional and tissue-specific expression of the Ca2+/calmodulin-dependent protein kinase, CaM kinase-Gr, were examined. The Mr 65,000 alpha-polypeptide of CaM kinase-Gr is expressed ubiquitously in different anatomical regions of rat brain, whereas an additional Mr 67,000 beta-polypeptide is observed solely in the cerebellum. The alpha-polypeptide appears in the neonatal rat forebrain and cerebellum, whereas the beta-polypeptide appears by the second postnatal week and may reflect cerebellar granule cell differentiation. Most peripheral tissues do not express either CaM kinase-Gr polypeptide. However, rat thymus and thymocytes derived therefrom express CaM kinase-Gr at levels comparable to those of the central nervous system. The identity of the enzyme in rat thymus was corroborated by immunoblot assays, Northern blots, and direct enzyme purification. Rat spleen and testis also produce CaM kinase-Gr, but at lower levels than either thymus or brain. These observations demonstrate selective regional and developmental expression of CaM kinase-Gr polypeptide in brain, and suggest that it may participate in Ca2+ signalling in cells derived both from the immune system as well as the central nervous system. PMID- 1894641 TI - Tandem mass spectrometry identifies sites of three post-translational modifications of spinach light-harvesting chlorophyll protein II. Proteolytic cleavage, acetylation, and phosphorylation. AB - The photosynthetic membranes of spinach (Spinacia oleracea L.) chloroplasts were incubated with [gamma-32P] ATP. When the thylakoid membrane kinase was activated with light, the 25- and 27-kDa forms of the light-harvesting chlorophyll a/b protein (LHC II) were phosphorylated on their amino termini. Treatment of the membranes with proteinase K or thermolysin released phosphopeptides which were purified by ferric ion affinity chromatography and reverse phase high performance liquid chromatography. Sequencing of the phosphopeptides was performed with tandem quadrupole mass spectrometry. Three different phosphopeptides Ac RKTAGKPKT, Ac-RKTAGKPKN, and Ac-RKSAGKPKN originating from class I LHC II were examined after release by thermolysin. One phosphopeptide, Ac-RRTVKSAPQ, originating from class II LHC II was examined after release by proteinase K. Each of the four LHC II phosphopeptides was derived from the amino terminus of a distinct protein. Peptides were acetylated at their amino-terminal arginine and were phosphorylated on either threonine or serine in the third position. We conclude that proteolytic processing of pre-LHC II occurs at a conserved methionyl-arginyl bond and is followed by amino-terminal acetylation of the arginine and nearby phosphorylation of the mature LHC II. Eight different peptides were synthesized in acetylated and nonacetylated forms as substrates for the thylakoid membrane kinase. From a comparison of the kinetics of phosphate incorporation into the peptides, we conclude that basic residues on both sides of the phosphorylation site are important for enzyme recognition. Acetylation of the amino terminus is not required for phosphorylation. PMID- 1894643 TI - Reductive methylation of the amino terminus of endonuclease V eradicates catalytic activities. Evidence for an essential role of the amino terminus in the chemical mechanisms of catalysis. AB - Endonuclease V, a pyrimidine dimer-specific DNA repair enzyme, was chemically modified by reductive methylation, a technique that specifically methylates primary amino groups. Upon reaction of endonuclease V with [14C]formaldehyde (14CH2O) in the presence of the reducing agent sodium cyanoborohydride (Na CNBH3), it was discovered that 0.8 methylation/endonuclease V molecule was required to reduce both the glycosylase and the phosphodiester lyase activities by 70-80%. Pyrimidine dimer-specific binding was not eradicated at a level of methylation equivalent to 0.8 CH3/endonuclease V molecule but was eradicated at higher levels of methylation. Endonuclease V that had been modified with an average of 1.6 CH3/molecule was digested with Staphylococcus aureus strain V8 protease and the peptides subsequently separated by reverse-phase high performance liquid chromatography. Radiolabel was found exclusively on the peptide including the amino terminus, as determined by the percent amino acid composition. Neither intact CH3-endonuclease V nor radiolabeled peptides were able to be sequenced by Edman degradation indicating blockage of the amino terminus by methylation. This study shows strong evidence for the unusual involvement of the alpha NH2 moiety in the chemical mechanisms of endonuclease V. A reaction mechanism that incorporates these findings is presented. PMID- 1894644 TI - Effects of platelet-derived growth factor and transforming growth factor-beta 1 on the synthesis of a large versican-like chondroitin sulfate proteoglycan by arterial smooth muscle cells. AB - Platelet-derived growth factor (PDGF) and transforming growth factor-beta 1 (TGF beta 1) increase [35S]sulfate incorporation into proteoglycan (PG) by monkey arterial smooth muscle cells but have opposite effects on cell proliferation. The combination of these two growth regulatory peptides has an additive effect on PG synthesis but no effects on cell proliferation. The time course of sulfate incorporation after stimulation indicates that both growth factors cause maximal incorporation of sulfate into glycosaminoglycan chains by 12-18 h. The PG that is most affected is a large CSPG (Mr approximately 1.2 x 10(6)) which can be immunoprecipitated by an antibody against versican, a large CSPG synthesized by human skin fibroblasts. The hydrodynamic size of this molecule increases after PDGF and TGF-beta 1 stimulation, but the size of the core glycoprotein (Mr approximately 450,000) remains the same. Treatment with either growth factor leads to an increase in the amount of core glycoprotein for this PG. This increase correlates with an increase in the steady state level of mRNA identified by hybridization to a cDNA encoding versican. The two growth factors also increase the glycosaminoglycan chain length of this PG accounting for the greater hydrodynamic size of the molecule after stimulation. In contrast, PDGF and not TGF-beta 1 changes the composition of the glycosaminoglycan chains attached to this PG by doubling the ratio of chondroitin 6-sulfate to chondroitin 4-sulfate. These results indicate that although both of these growth factors increase the net synthesis of a large versican like CSPG, they differ in their effects on the structure of the glycosaminoglycan chains. These post-translational modifications may relate to the growth state of the cells. PMID- 1894645 TI - A mutated transferrin receptor lacking asparagine-linked glycosylation sites shows reduced functionality and an association with binding immunoglobulin protein. AB - The function of the transferrin receptor is to transport iron-bound transferrin into the cell. In order to function properly, this dimeric glycoprotein must be expressed on the cell surface and be able to bind transferrin. Site-directed mutagenesis was performed to abolish the three asparagine-linked glycosylation consensus sequences of the human transferrin receptor. The DNA encoding the mutated transferrin receptor was stably transfected into mouse fibroblasts. This form of the human transferrin receptor shows reduced transferrin binding, reduced intersubunit bond formation, and reduced cell surface expression, indicating that the transferrin receptor which lacks asparagine-linked glycosylation is not fully functional. In addition, the mutated form of the receptor is not processed as quickly. It shows an association with an endoplasmic reticular chaperone protein, binding immunoglobulin protein, leading to the hypothesis that the mutated transferrin receptor experiences increased retention in the endoplasmic reticulum. PMID- 1894646 TI - Membrane topology of Escherichia coli prolipoprotein signal peptidase (signal peptidase II). AB - The lsp gene of Escherichia coli encodes the inner membrane enzyme, signal peptidase II (SPase II). SPase II is comprised of 164 amino acid residues and contains four hydrophobic domains. A series of lsp-phoA and lsp-lacZ gene fusions have been constructed in vitro to determine the topology of SPase II. The fusion junction for each of these gene fusions was determined by DNA sequencing. The lengths of the SPase II fragment in the fusions varied from 12 to 159 amino acid residues. Strains containing SPase II-PhoA fusions to the two predicted periplasmic loops exhibited higher levels of alkaline phosphatase activity than fusions to the predicted cytoplasmic domains. In contrast, SPase II-LacZ fusions at the cytoplasmic and the periplasmic domains of SPase II showed high and low levels of beta-galactosidase activity, respectively, a result opposite to those shown by SPase II-PhoA fusions located at precisely the same amino acid of SPase II. Taken together, these results strongly support the predicted model for SPase II topology, i.e. this enzyme spans the cytoplasmic membrane four times with both the amino and the carboxyl termini facing the cytoplasm. PMID- 1894648 TI - Biosynthesis of fibronectin by rabbit aorta. AB - The in vitro interactions between vascular cells and fibronectin have been shown to influence phenotypic expression of both cultured endothelial and smooth muscle cells. To more effectively assess the potential functional role of fibronectin in vivo in modulating vascular phenotypes, we have established methodology for studying fibronectin biosynthesis in the rabbit aorta using aortic rings that are morphologically and functionally intact and metabolically active. Aortic rings were incubated with 35S-labeled methionine in a supplemented physiological salt solution. The tissue was fractionated, and quantitative immunoprecipitation was performed using a polyclonal antibody directed against human plasma fibronectin. Newly synthesized fibronectin was most abundant in the fraction solubilized using 4% sodium dodecyl sulfate and in the incubation medium. In all fractions studied, fibronectin was present predominantly as a dimer with no detectable aggregates of fibronectin. Pulse-chase experiments showed that a substantial amount of newly synthesized fibronectin was found in the 4% sodium dodecyl sulfate extract after only 1 h, suggesting that fibronectin was rapidly incorporated into the extracellular matrix. The more soluble forms of newly synthesized fibronectin appeared to be the precursors for secreted fibronectin, and no precursor-product relationship between soluble and insoluble fibronectin was found. Dissection of aortic rings following incubation with labeled methionine showed that newly synthesized fibronectin was uniformally distributed in both intima-media and media-adventitia segments. Endothelial cell denudation caused only a 20% decrease of fibronectin biosynthesis concomitant with similar changes in total protein biosynthesis, consistent with the medial smooth muscle cell as the major source of newly synthesized fibronectin. Biosynthesis of fibronectin was increased following a 24-h preincubation of the aortic rings, and concomitant increases in steady state mRNA for fibronectin were found. These in vitro studies documented the utility of aortic rings for the general purpose of studying protein synthesis in vascular cells and provide new information on the characteristics of fibronectin biosynthesis by aortic tissue. PMID- 1894647 TI - Selective inhibition of isoprenylation of 21-26-kDa proteins by the anticarcinogen d-limonene and its metabolites. AB - Limonene has chemotherapeutic activity against chemically induced rat mammary carcinomas, many of which contain activated ras genes. Given the recent discovery of the post-translational modification of p21ras and other cell growth-associated proteins by intermediates in the mevalonic acid pathway, and the common biochemical origins of limonene and these isoprene products, we investigated the effect of limonene on protein isoprenylation. NIH3T3 and human mammary epithelial cells were incubated with lovastatin and [2-14C]mevalonolactone in the absence and presence of limonene. Labeled proteins were then subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis and fluorography. Limonene inhibited isoprenylation of a class of cellular proteins of 21-26 kDa, including p21ras and possibly other small GTP-binding proteins, in a dose-dependent manner in both cell lines. In contrast, limonene did not affect the isoprenylation of several other proteins, including nuclear lamins. Limonene is metabolized extensively in vivo but not in cultured cells. The two major rat serum metabolites of limonene, perillic acid and dihydroperillic acid, were more potent than limonene in the inhibition of isoprenylation. These results demonstrate that limonene selectively inhibits isoprenylation of 21-26-kDa proteins at a point in the mevalonic acid pathway distal to 3-hydroxy-3-methylglutaryl coenzyme A reductase, and they provide a plausible explanation for its chemotherapeutic activity. Inhibition of isoprenylation of proteins such as p21ras and other small GTP-binding proteins would alter their intracellular localization and, hence, disrupt their biological activity. PMID- 1894649 TI - Inhibition of proteinase K by methoxysuccinyl-Ala-Ala-Pro-Ala-chloromethyl ketone. An x-ray study at 2.2-A resolution. AB - The crystal structure of the transition state analog complex formed covalently between proteinase K and methoxysuccinyl-Ala-Ala-Pro-Ala-chloromethyl ketone was determined by x-ray diffraction methods at a resolution of 2.2 A and refined by constrained least squares to an R factor of 19.8% for the 11864 structure amplitudes greater than 1 sigma F. The chloromethyl ketone group is covalently linked with the active site functional groups His69(N epsilon) and Ser224(O gamma). The former has substituted for chlorine and the latter has attacked the carbon of the ketone group, thereby forming the tetrahedral carbon atom of the transition state analog. The peptide part of the inhibitor is in an extended conformation and fills subsites S1 to S5 of the substrate recognition site. Its backbone hydrogens bond with strands 100-104 and 132-136 of the substrate recognition site as the central strand of a three-stranded antiparallel beta pleated sheet. This sheet formation is associated with a movement by approximately 1 A of strand 100-104 which is probably associated with the insertion of the bulky proline side chain. The methoxysuccinyl group is stacked on the phenolic side chain of Tyr104 that is a part of the bottom of the recognition site. Biochemical studies show that shorter inhibitors of this type are less effective than the longer one, because there are fewer hydrogen bonding and van der Waals/stacking interactions. PMID- 1894650 TI - p21 with a phenylalanine 28----leucine mutation reacts normally with the GTPase activating protein GAP but nevertheless has transforming properties. AB - The H-ras gene product p21H has been mutated at Phe-28, which makes a hydrophobic interaction with the guanine base of bound GDP/GTP. The mutation Phe-28----Leu drastically increases nucleotide dissociation rates without affecting association rates. This is due to a perturbed binding of base, alpha- and beta-phosphate, and Mg2+, as evidenced from 31P NMR and fluorescence measurements. The region around the gamma-phosphate appears normal. The affinity of Mg2+ for both the di- and the triphosphate conformation of the mutant was also measured by fluorescence. The association constant is 3.5 x 10(7) M-1 for the Gpp(NH)p complex, 500 times higher than for the GDP form. The mutation does not change appreciably the intrinsic or the GTPase activating protein (GAP)-stimulated GTPase. The mutated protein induces neurite differentiation however when pressure-loaded into PC12 cells, which is equivalent to transformation of NIH 3T3 cells. This shows that p21 (F28L) is converted to the GDP bound form by GAP but is transforming because the high dissociation rate for nucleotides leads to a protein predominantly in the active GTP bound form. PMID- 1894651 TI - Human alpha 1 (XIII) collagen gene. Multiple forms of the gene transcripts are generated through complex alternative splicing of several short exons. AB - The structure of the gene for the human alpha 1(XIII) collagen chain (COL13A1) was determined from genomic clones spanning 140,000 base pairs (bp), including about 3,000 bp of the 5'-end-flanking region and 5,000 bp of the 3'-end-flanking region. The gene was shown to contain 39 exons. There were eight exons of 27 bp, five of 36 bp, four of 54 bp, three of 45 bp, and two of 42 bp. The rest of the exons coding for translated sequences had sizes varying between 24 and 153 bp. The genomic clones did not contain exons 3 and 4 whose sizes could, however, be estimated from cDNA clones. S1 nuclease mapping and primer extension analyzes indicated five closely spaced initiation sites of transcription. Sequencing of the 5'-end-flanking region did not reveal a typical TATA box but a four times repeated TATTTAT sequence that may serve as true TATA boxes. Two CCAAT boxes were found starting at positions-13 and -194, and furthermore, the promoter region contains two GC boxes. Previous studies on alpha 1 (XIII) collagen cDNA and genomic clones showed that the primary transcript undergoes complex alternative splicing generating at least four different forms of mRNAs. The present work demonstrated that sequences of seven exons are alternatively used. These exons contain sequences coding for pure collagenous regions, pure noncollagenous regions, and an exon coding for a junction of a collagenous and noncollagenous domain. PMID- 1894653 TI - Bone grafts. PMID- 1894652 TI - Hydroxyapatite coating of prostheses. PMID- 1894654 TI - AIDS and the orthopaedic surgeon. PMID- 1894655 TI - Coronal alignment after total knee replacement. AB - Maquet's line passes from the centre of the femoral head to the centre of the body of the talus. The distance of this line from the centre of the knee on a long-leg radiograph provides the most accurate measure of coronal alignment. Malalignment causes abnormal forces which may lead to loosening after knee replacement. We report a series of 115 Denham knee replacements performed between 1976 and 1981 using the earliest design of components, inserted with intramedullary guide rods. Patients were assessed clinically and long-leg standing radiographs were taken before operation, soon after surgery and up to 12 years later. In two-thirds of the knees (68%) Maquet's line passed through the middle third of the prosthesis on postoperative films and the incidence of subsequent loosening was 3%. When Maquet's line was medial or lateral to this, an error of approximately +/- 3 degrees, the incidence of loosening at a median period of eight years was 24%. This difference is highly significant (p = 0.001). Accurate coronal alignment appears to be an important factor in prevention of loosening. Means of improving the accuracy of alignment and of measuring it on long-leg radiographs are discussed. PMID- 1894656 TI - A quantitative approach to radiography of the lower limb. Principles and applications. AB - A method is described which provides standardised reproducible radiographic images of the lower limb. Anteroposterior and lateral radiographs are digitised and processed by computer to provide graphic/numeric displays of angles and linear measurements, relating the centre points of the hip, knee, and ankle. Two cases illustrate how surgical planning is facilitated when standardised data are available. These data confirm the close relationship between postoperative limb alignment and positioning of prosthetic elements. PMID- 1894657 TI - Measurement of lower limb alignment using long radiographs. AB - Long radiographs are used to measure lower limb axial alignment, to assess the progression of deformity, and to plan corrective surgery. The purpose of this study was to test the belief that jigs are necessary in order to control limb position for radiography. Above-knee amputated limbs were fixed in different positions of rotation and of knee flexion and radiographed to study the effect on the apparent alignment of the limb. If the limb was rotated no more than 10 degrees from the neutral the effect on apparent axial alignment was minimal and radiographic measurement was reliable. This suggests that standardised positioning jigs are not needed in routine clinical practice. PMID- 1894658 TI - Measurement of hip prostheses using image analysis. The maxima hip technique. AB - A computer-based image analysis system has been developed as a research tool in total hip replacement. The system has been programmed to take multiple measurements from coronal plane radiographs. Poor quality radiographic images can be enhanced and standardised. The measurements which can be obtained include stem subsidence, cup migration, cup wear, and stem loosening. Reproducibility and accuracy were +/- 0.01 mm and +/- 0.5 mm respectively. The present application is in retrospective research, but prospective monitoring of radiographs is planned. PMID- 1894659 TI - Survivorship analysis and confidence intervals. An assessment with reference to the Stanmore total knee replacement. AB - Survivorship analysis is a useful way of expressing the long-term results of joint replacement: it provides a means of comparing the life span of one type of prosthesis with another. However, such studies should include a full life-table and the confidence intervals for the survival rates at given times. At least 40 surviving prostheses are required to provide reliable results. PMID- 1894660 TI - Arthroscopic stapling for detached superior glenoid labrum. AB - Superior labral tears of the shoulder involve the biceps tendon and labrum complex which may be detached, displaced inferiorly, and interposed between the glenoid and the humeral head. We have treated ten young athletes with painful shoulders due to this lesion by arthroscopic stapling. Arthroscopy at the time of staple removal, after three to six months, showed that all the lesions had been stabilised. Clinical review at over 24 months showed an excellent or good result in 80%. The two relative failures were due in one to residual subacromial bursitis, and the other to multidirectional shoulder instability. Arthroscopic stapling can restore the shoulder anatomy, and it is recommended for active adolescent athletes with this lesion. PMID- 1894661 TI - Revision of failed knee replacements using fixed-axis hinges. AB - Forty failed hinged arthroplasties of the knee were revised by the insertion of another hinged implant. In 14 cases the prosthesis used at the revision operation was similar to the primary implant; in 26, a hinge with an elongated femoral stem was used, usually replacing part of the femoral shaft. In seven of these knees an elongated tibial stem was also required, though the tibial shaft was replaced in only two of them. There were many complications. Fracture of the femur at the tip of the femoral stem was the most frequent. Sixteen first revisions failed and were revised a second time; 12 required replacement of the distal femoral shaft and three required replacement of the proximal tibia. The incidence of complications in knees requiring a second revision was even higher. Four required a third revision after an average interval of three years. Failure of a hinged prosthesis results in bone loss mainly in the femur. Revision of a failed hinged prosthesis with another of the same design is unlikely to be successful and may cause fracture of the femur. PMID- 1894662 TI - Prosthetic replacement of the distal femur for primary bone tumours. AB - Over a 16-year period, 135 custom-made distal femoral prostheses, based on a fully constrained Stanmore-type knee replacement, were used in the treatment of primary malignant or aggressive benign tumours. Survivorship analysis showed a cumulative success rate of 72% at five years and 64% at seven years. Intact prostheses in 91% of the surviving patients gave good or excellent functional results. Deep infection was the major complication, occurring in 6.8% of cases; clinical aseptic loosening occurred in 6.0%. Revision surgery was carried out for loosening and infection, and the early results are encouraging. We conclude that prosthetic replacement of the distal femur can meet the objectives of limb salvage surgery. PMID- 1894663 TI - Total hip replacement for juvenile chronic arthritis. AB - We review the results of 96 primary total hip replacements in 54 patients with juvenile chronic arthritis at five years or longer after surgery. The mean age at operation was 16.7 years (range 11.25 to 26.6); the follow-up period averaged 11.5 years. The clinical results in terms of pain, range of movement, mobility and function are presented. A revision procedure was required in 24 hips (25%) in 18 patients at an average of 9.5 years after the primary operation. A further 17 hips had radiographic signs of loosening. The factors thought to contribute to this relatively high failure rate in patients with juvenile chronic arthritis are discussed. PMID- 1894664 TI - Quantifying bone loss from the proximal femur after total hip arthroplasty. AB - To define the natural history of bone loss around a femoral prosthesis, the bone mineral content and bone mineral density were measured for each femur in 28 patients with unilateral total hip arthroplasty, 18 age-matched controls, and seven patients with unilateral osteoarthritis. The areas measured were inside the lesser trochanter and 4.8 cm distal to it. The contralateral hip served as the control. Three years after arthroplasty there was 40% loss in average bone mineral content inside the lesser trochanter, and 28% loss in average bone mineral content 4.8 cm distally in the medial cortex. At seven to 14 years after operation, patients had lost 40% of bone proximally and 49% distally. The data suggest that this may progress in a proximal-to-distal fashion, and could account for a 50% decrease in bone mass seven to 14 years after surgery. PMID- 1894665 TI - Effect of hypotensive epidural anaesthesia on acetabular cement-bone fixation in total hip arthroplasty. AB - We selected 20 matched pairs of patients who had had total hip arthroplasty by the same surgeon using the same cemented technique. Matching was by age, sex, height, weight and diagnosis. One of each pair had received hypotensive epidural anaesthesia, with less than 300 ml blood loss: the other had normotensive general anaesthesia with more than 500 ml of blood loss. Early postoperative radiographs were evaluated independently by three blinded observers, using a scoring criteria which assessed the quality of the cement-bone interface. The results showed that patients who had received epidural anaesthesia had significantly better radiographic scores (p less than 0.02). Our findings suggest that hypotensive anaesthesia facilitates penetration of cement into bone. PMID- 1894666 TI - Total arthroplasty of the hip after childhood sepsis. AB - Total hip arthroplasty was performed in 45 hips of 44 patients who had pyogenic arthritis of the hip during childhood. The average age of the patients was 36.4 years (range 19 to 50). The interval between active infection and arthroplasty ranged from 11 to 40 years, and average follow-up was 65.4 months (range 58 to 80). Specimens of tissue taken before and during operation gave negative cultures in all hips, and no patient had reactivation of infection. The mean functional rating of the hips was 58 points before operation and 90 at the final review. Complications were seen in 11 cases (24%), loosening of components occurred in six (13%) and one hip had to be revised for acetabular component migration. Acetabular allografts were required in 27 hips (60%). All allografts united but there was partial resorption of the graft in the non-weight-bearing area in all. PMID- 1894667 TI - Fresh autogeneic, frozen allogeneic, and decalcified allogeneic bone grafts in dogs. AB - In fully-grown mongrel dogs, diaphyseal ulnar defects 25 mm long were stabilised by screws and plates, and were temporarily filled with silicone rubber blocks. After eight weeks the block was replaced either by fresh autogeneic cancellous bone, allogeneic deep-frozen cancellous bone, allogeneic decalcified bone matrix, or bone matrix gelatin. After 24 weeks the implants were evaluated by radiography, histology, and measurements of new bone volume, using computer assisted density registration on microradiographs. Only the autogeneic bone grafts led to healing in all instances. Bone regeneration in the other groups was not significantly better than in the sham group in which no graft was employed. Decalcified bone matrix proved ineffective. PMID- 1894668 TI - The mechanical and biological properties of demineralised cortical bone allografts in animals. AB - We studied the calcium content and mechanical strength of cortical bone from rats and dogs after different periods of demineralisation, showing that the rate of demineralisation differed considerably between the species. Specimens from the rat were further treated by chemical extraction and autolysis and tested for osteoinductive properties. We showed that partially demineralised cortical bone retained adequate mechanical strength, while retaining the biological effects of completely demineralised bone. This shows that it is possible to prepare allografts which have adequate mechanical strength and still retain osteo inductive properties. PMID- 1894669 TI - Three-dimensional collagen architecture in bovine articular cartilage. AB - The three-dimensional architecture of bovine articular cartilage collagen and its relationship to split lines has been studied with scanning electron microscopy. In the middle and superficial zones, collagen was organised in a layered or leaf like manner. The orientation was vertical in the intermediate zone, curving to become horizontal and parallel to the articular surface in the superficial zone. Each leaf consisted of a fine network of collagen fibrils. Adjacent leaves merged or were closely linked by bridging fibrils and were arranged according to the split-line pattern. The surface layer (lamina splendens) was morphologically distinct. Although ordered, the overall collagen structure was different in each plane (anisotropic) a property described in previous morphological and biophysical studies. As all components of the articular cartilage matrix interact closely, the three-dimensional organisation of collagen is important when considering cartilage function and the processes of cartilage growth, injury and repair. PMID- 1894670 TI - Reconstruction of lateral ligaments of the ankle with allogeneic tendon grafts. AB - Fresh frozen allogeneic tendon was used to reconstruct the lateral ligaments in 17 ankles. Two or more years later, 13 returned for follow-up examination. The mean age at operation was 23 years (range 15 to 39); the interval between injury and operation varied from six months to 20 years. There were no infections and no immunological rejections, and according to Sefton's criteria, nine patients were excellent and four good. No patient complained of instability of the ankle and stress radiography confirmed this improvement. Allograft reconstruction of the lateral ligaments of the ankle is a new method of treatment which restores stability without sacrificing normal tendons. PMID- 1894671 TI - Polyethylene wear from retrieved acetabular cups. AB - Laboratory wear testing of ultra high molecular weight polyethylene from 12 Charnley acetabular cups, removed after periods of up to 17.5 years showed that the large patient-to-patient variations in clinical penetration rate cannot be explained by batch-to-batch variation in the wear resistance of the material. Nor was there any evidence of a time-dependent degradation in wear resistance of the material. PMID- 1894672 TI - Ultraviolet radiation compared to an ultra-clean air enclosure. Comparison of air bacteria counts in operating rooms. AB - Clean air in the operating room is important during joint replacement surgery. We compared monochromatic ultraviolet radiation of 254 nm with the use of a Charnley Howorth air enclosure by bacterial air-sampling during 113 total hip arthroplasties. Air samples were taken continuously at the edge of the wound and every 15 minutes at a site 130 cm from the operating table. We also tested the effect of occlusive clothing for all personnel. Ultraviolet light was more efficient than the ultra-clean air enclosure, and occlusive clothing on its own or in combination also produced improvement. The implications of these findings are discussed. PMID- 1894673 TI - Prediction of amputation after severe lower limb trauma. AB - The Mangled Extremity Severity Score was applied to 152 patients with severely injured lower limbs. All cases with a score of seven or more required amputation; some with scores of less than seven eventually came to amputation. These observations are discussed. PMID- 1894674 TI - The effect of devascularisation upon early bone healing in dynamic external fixation. AB - We examined the effect of periosteal devascularisation upon the early healing of osteotomies of sheep tibiae held in an instrumented external fixation system with an axial stiffness of 240 N/mm. At 14 days, cortical blood flow measured by the microsphere technique was 19.3 ml/min/100g in the well-vascularised osteotomies, but only 1.7 ml/min/100g in the devascularised osteotomies, despite an increase in medullary flow (p less than 0.0005). Delay in healing of the devascularised osteotomies was suggested by an in vivo monitoring system and confirmed by post mortem mechanical testing. We suggest that the osteogenic stimulus of dynamic external fixation is dependent on the early restoration of cortical blood flow in devascularised fractures. PMID- 1894675 TI - Intracapsular fractures of the neck of femur. Parallel or crossed garden screws? AB - The results of treatment in 242 patients with intracapsular fractures of the neck of femur treated with Garden screws are presented with reference as to whether the screws were crossed or parallel. The incidence both of nonunion and of avascular necrosis was less in those fractures treated with parallel screws. The outcome was also superior if the reduction was good. PMID- 1894676 TI - Need the thumb be immobilised in scaphoid fractures? A randomised prospective trial. AB - Immobilisation of the thumb is widely believed to be important in the management of fractures of the carpal scaphoid. To assess the need for this, we randomly allocated 392 fresh fractures for treatment by either a forearm gauntlet (Colles') cast, leaving the thumb free, or by a conventional 'scaphoid' plaster incorporating the thumb as far as its interphalangeal joint. In the 292 fractures which were followed for six months, the incidence of nonunion was independent of the type of cast used. PMID- 1894677 TI - Proprioception and function after anterior cruciate reconstruction. AB - We have assessed 45 patients who had undergone anterior cruciate reconstruction by a modified MacIntosh-Jones method. The results, using standard knee scores and clinical ligament testing, correlated poorly with the patient's own opinion and with the functional result. However, measurement of proprioception in the knee correlated well with both function (r = 0.84) and with patient satisfaction (r = 0.9). This study indicates that proprioception, rather than the clinical excellence of the repair, is a major factor in the outcome of anterior cruciate ligament reconstruction. PMID- 1894678 TI - Distal transfer of the greater trochanter. AB - After congenital dislocation of the hip, Perthes' disease and some other conditions, the femoral neck may be short and the greater trochanter in a relatively proximal position. Distal transfer of the greater trochanter is an effective and relatively simple operation to correct this deformity. We have reviewed 26 patients (27 hips) at a mean follow-up of eight years. Pain relief and improvement in gait were maintained in 74%, and the poor results were largely due to progression of osteoarthritis. We describe a 'gear-stick' sign of trochanteric impingement, which is useful in the pre-operative assessment of patients. PMID- 1894679 TI - Pachydysostosis of the fibula. AB - We report four patients with unilateral bowing of the lower leg, affecting only the fibula. The bone is too long with anterolateral curvature of the distal third. Because of its regressive course and the absence of cutaneous involvement, this newly described entity can be distinguished from other forms of bowing of the leg. PMID- 1894680 TI - Vascularised fibular graft for congenital pseudarthrosis of the tibia. Long-term results. AB - Five children with congenital pseudarthrosis of the tibia treated by free vascularised fibular grafts were followed up until skeletal maturity. The ipsilateral fibula was used in four cases, the contralateral fibula in one. All our cases achieved bone union, but leg length discrepancy, atrophy of the foot and ankle stiffness were frequent complications, due perhaps to the many previous operations. Vascularised fibular grafting might achieve better results if it were done as the primary procedure. PMID- 1894681 TI - Progressive noninfectious anterior vertebral fusion. AB - We reviewed 26 patients with progressive spinal kyphosis due to anterior fusion between the vertebrae. No patient had back pain or any neurological defect. The kyphosis appeared to be progressive until the fusion had included all of the disc. Progression was faster during the adolescent growth-spurt. Kyphosis increased with the number of discs involved, from one to six, and the extent of fusion within each disc. In six of the nine cases treated by spinal bracing, progression of the kyphosis was arrested. PMID- 1894682 TI - Bilateral avascular necrosis of the talus following strenuous physical activity. PMID- 1894684 TI - Safe pin-drilling in Ilizarov's percutaneous transfixation method. PMID- 1894683 TI - Freiberg's disease and dorsiflexion osteotomy. PMID- 1894685 TI - Iliac wing storage of femoral head autograft. PMID- 1894686 TI - Bone graft harvesting: a percutaneous technique. PMID- 1894687 TI - Use of tourniquets. PMID- 1894688 TI - Taking a bone graft. PMID- 1894689 TI - Fatty lesions in bone. PMID- 1894690 TI - Two forms of elongation factor 1 alpha (EF-1 alpha O and 42Sp50), present in oocytes, but absent in somatic cells of Xenopus laevis. AB - We have purified and partially sequenced the EF-1 alpha protein from Xenopus laevis oocytes (EF-1 alpha O). We show that the two cDNA clones isolated by Coppared et al. (Coppard, N. J., K. Poulsen, H. O. Madsen, J. Frydenberg, and B. F. C. Clark. 1991. J. Cell Biol. 112:237-243) do not encode 42Sp50, as claimed by these authors, but two very similar forms of EF-1 alpha O (EF-1 alpha O and EF-1 alpha O1). 42Sp50 is the major protein component of a 42S nucleoprotein particle that is very abundant in previtellogenic oocytes of X. laevis, 42Sp50 differs from EF-1 alpha O not only by its amino acid sequence, but also by several properties already reported. In particular, 42Sp50 has a low EF-1 alpha activity. It is distributed uniformly in the cytoplasm of previtellogenic oocytes, in contrast to EF-1 alpha O which is concentrated in a small region of the cytoplasm, known as the mitochondrial mass or Balbiani body. PMID- 1894691 TI - Targeting of frog prodermorphin to the regulated secretory pathway by fusion to proenkephalin. AB - We have investigated the sorting and processing of the amphibian precursor prepro dermorphin in mammalian cells. Dermorphin, a D-alanine-containing peptide with potent opioid activity, has been isolated from the skin of the frog Phyllomedusa sauvagei. The maturation of this peptide from the precursor involves several posttranslational steps. Recombinant vaccinia viruses were used to infect AtT-20, PC12, and HeLa cells to study the sorting and processing of prepro-dermorphin. While this precursor was not processed in any of the examined cell lines, AtT-20 cells were able to process approximately 40% of a chimeric precursor consisting of the first 241 amino acids of prepro-enkephalin fused to a carboxy-terminal part of pro-dermorphin. By immunogold-EM, we could show that the chimeric protein, but not pro-dermorphin, was sorted to dense-core secretion granules. The processing products could be released upon stimulation by 8-Br-cAMP. We conclude that the pro-enkephalin part of the fusion protein contains the information for targeting to the regulated pathway of secretion, while this sorting information is missing in pro-dermorphin. This indicates that sorting mechanisms may differ between amphibian and mammalian cells. PMID- 1894692 TI - PAS3, a Saccharomyces cerevisiae gene encoding a peroxisomal integral membrane protein essential for peroxisome biogenesis. AB - Saccharomyces cerevisiae pas3-mutants are described which conform the pas phenotype recently reported for the peroxisomal assembly mutants pas1-1 and pas2 (Erdmann, R., M. Veenhuis, D. Mertens, and W.-H Kunau, 1989, Proc. Natl. Acad. Sci. USA. 86:5419-5423). The isolation of pas3-mutants enabled us to clone the PAS3 gene by functional complementation. DNA sequence analysis revealed a 50.6-kD protein with at least one domain of sufficient length and hydrophobicity to span a lipid bilayer. To verify these predictions antibodies were raised against a truncated portion of the PAS3 coding region overexpressed in E. coli. Pas3p was identified as a 48 kD peroxisomal integral membrane protein. It is shown that a lack of this protein causes the peroxisome-deficient phenotype and the cytosolic mislocalization of peroxisomal matrix enzymes. Based on protease digestion experiments Pas3p is discussed to be anchored in the peroxisomal membrane by its amino-terminus while the bulk of the molecule is exposed to the cytosol. These findings are consistent with the possibility that Pas3p is one component of the peroxisomal import machinery. PMID- 1894693 TI - Stopped-flow measurement of cytoskeletal contraction: Dictyostelium myosin II is specifically required for contraction of amoeba cytoskeletons. AB - Cytoskeletons provide valuable information on the composition and organization of the cell's contractile machinery, and in many cases these cell models retain the ability to contract. To quantitate contraction rates, we developed a novel stopped-flow assay permitting simultaneous analysis of thousands of Dictyostelium cytoskeletons within milliseconds of mixing with Mg-ATP. Cytoskeletons were placed in one syringe of the stopped flow apparatus and the appropriate buffer was placed in the second syringe. Mixing with Mg-ATP caused an immediate increase in the absorbance at 310 nm. Rapid fixation of the cytoskeletons during the reaction confirmed that this change in absorbance was highly correlated with contraction of the cytoskeletons. This spectroscopic change was used to measure the effects of temperature, pH, ionic strength, and nucleotides on contraction rate. Treatment with high salt and ATP removed most of the myosin, some actin, and small amounts of minor proteins. These extracted cytoskeletons lost the ability to contract, but after the addition of purified Dictyostelium myosin they regained full function. In contrast, rabbit skeletal muscle myosin was unable to restore contractility, even though it bound to the extracted cytoskeletons. Cytoskeletons prepared from a myosin-null mutant did not contract. Upon the addition of purified ameba myosin, however, they became contractile. These results suggest that filamentous Dictyostelium myosin II is essential for contraction, and that the actin cytoskeleton and associated proteins retain their functional organization in the absence of myosin. PMID- 1894694 TI - Microtubule sliding in swimming sperm flagella: direct and indirect measurements on sea urchin and tunicate spermatozoa. AB - Direct measurements of microtubule sliding in the flagella of actively swimming, demembranated, spermatozoa have been made using submicron diameter gold beads as markers on the exposed outer doublet microtubules. With spermatozoa of the tunicate, Ciona, these measurements confirm values of sliding calculated indirectly by measuring angles relative to the axis of the sperm head. Both methods of measurement show a nonuniform amplitude of oscillatory sliding along the length of the flagellum, providing direct evidence that "oscillatory synchronous sliding" can be occurring in the flagellum, in addition to the metachronous sliding that is necessary to propagate a bending wave. Propagation of constant amplitude bends is not accomplished by propagation of a wave of oscillatory sliding of constant amplitude, and therefore appears to require a mechanism for monitoring and controlling the bend angle as bends propagate. With sea urchin spermatozoa, the direct measurements of sliding do not agree with the values calculated by measuring angles relative to the head axis. The oscillation in angular orientation of the sea urchin sperm head as it swims appears to be accommodated by flexure at the head-flagellum junction and does not correspond to oscillation in orientation of the basal end of the flagellum. Consequently, indirect calculations of sliding based on angles measured relative to the longitudinal axis of the sperm head can be seriously inaccurate in this species. PMID- 1894695 TI - Immunocytochemical localization of casein kinase II during interphase and mitosis. AB - We have developed specific antibodies to synthetic peptide antigens that react with the individual subunits of casein kinase II (CKII). Using these antibodies, we studied the localization of CKII in asynchronous HeLa cells by immunofluorescence and immunoelectron microscopy. Further studies were done on HeLa cells arrested at the G1/S transition by hydroxyurea treatment. Our results indicate that the CKII alpha and beta subunits are localized in the cytoplasm during interphase and are distributed throughout the cell during mitosis. Further electron microscopic investigation revealed that CKII alpha subunit is associated with spindle fibers during metaphase and anaphase. In contrast, the CKII alpha' subunit is localized in the nucleus during G1 and in the cytoplasm during S. Taken together, our results suggest that CKII may play significant roles in cell division control by shifting its localization between the cytoplasm and nucleus. PMID- 1894697 TI - [Surgical experience with 50 transplantations of neoprene-occluded segmental pancreas. Technique and postoperative complications]. AB - Since the beginning of our pancreas transplantation program in November, 1987, 50 patients have received a segmental intraperitoneal neoprene-occluded pancreas graft and a contralateral kidney graft. The aim of this study is to present our surgical technique and the postoperative complications encountered. Operation in the donor: subtotal pancreatectomy is performed. A venous patch is preserved at the end of the splenic vein. The splenic artery is removed with a patch taken from the end of the celiac trunk and the origin of the common hepatic artery, even in case of right (n = 1) or left (n = 4) hepatic artery. The canal is injected with neoprene (2 to 3 cc) ex vivo and the pancreatic parenchyma is recut after stappling. Operation in the recipient: the transplant is inserted in an extraperitoneal location, between the bladder and the pubic arch, then anastomosed to the external iliac vessels. RESULTS: All pancreas grafts functioned immediately. All patients but 3 are alive at present. Seven pancreas transplants were lost postoperatively due to venous thrombosis (n = 3), hemorrhage (n = 3) and death at D27 (n = 1). Many patients developed peripancreatic fluid collections and/or fistulae (the most frequent complication, probably due to the extraperitoneal site of transplantation). The actuarial survival rate of the patients, kidneys and pancreas after 2 years is 96%, 92% and 80%, respectively. PMID- 1894696 TI - Alternatively spliced type II procollagen mRNAs define distinct populations of cells during vertebral development: differential expression of the amino propeptide. AB - Type II collagen is a major component of cartilage providing structural integrity to the tissue. Type II procollagen can be expressed in two forms by differential splicing of the primary gene transcript. The two mRNAs either include (type IIA) or exclude (type IIB) an exon (exon 2) encoding the major portion of the amino (NH2)-propeptide (Ryan, M. C., and L. J. Sandell. 1990. J. Biol. Chem. 265:10334 10339). The expression of the two procollagens was examined in order to establish a potential functional significance for the two type II procollagen mRNAs. First, to establish whether the two mRNAs are functional, we showed that both mRNAs can be translated and the proteins secreted into the extracellular environment. Both proteins were identified as type II procollagens. Secondly, to test the hypothesis that differential expression of type II procollagens may be a marker for a distinct population of cells, specific procollagen mRNAs were localized in tissue by in situ hybridization to oligonucleotides spanning the exon junctions. Embryonic vertebral column was chosen as a source of tissue undergoing rapid chondrogenesis, allowing the examination of a variety of cell types related to cartilage. In this issue, each procollagen mRNA had a distinct tissue distribution during chondrogenesis with type IIB expressed in chondrocytes and type IIA expressed in cells surrounding cartilage in prechondrocytes. The morphology of the cells expressing the two collagen types was distinct: the cells expressing type IIA are narrow, elongated, and "fibroblastic" in appearance while the cells expressing type IIB are large and round. The expression of type IIB appears to be correlated with abundant synthesis and accumulation of cartilagenous extracellular matrix. The expression of type IIB is spatially correlated with the high level expression of the cartilage proteoglycan, aggrecan, establishing type IIB procollagen and aggrecan as markers for the chondrocyte phenotype. Transcripts of type II collagen, primarily type IIA, are also expressed in embryonic spinal ganglion. While small amounts of type II collagen have been previously detected in noncartilagenous tissues, the detection of this new form of the collagen in relatively high abundance in embryonic nerve tissue is unique. Taken together, these findings imply a potential functional difference between type IIA and type IIB procollagens and indicate that the removal of exon 2 from the pre-mRNA, and consequently the NH2-propeptide from the collagen molecule, may be an important step in chondrogenesis. In addition, type II procollagen, specifically type IIA, may function in noncartilage tissues, particularly during development. PMID- 1894698 TI - [Long-term results of surgical treatment for achalasia of the esophagus]. AB - 25 patients were operated with Heller's procedure for achalasia of the esophagus. A study of their clinical, radiological, manopetric and pH-metric evolution was carried out over an average period of 75 months. While the long-term results were satisfactory in 80% of these patients, the poor results were essentially caused by the occurrence of gastroesophageal reflux. An objective study performed by manometry and pH-metry allowed evidencing true asymptomatic acid reflux. It is necessary to devise an anti-reflux valve if the myotomy reaches as far as the cardia. PMID- 1894699 TI - [Peritoneal puncture dialysis in the monitoring and treatment of hemoperitoneum of traumatic origin?]. AB - The great diversity of injuries after abdominal wound, need an adapted treatment. When laparotomy is indicated in uncontrollable hemorrhage, peritoneal lavage associated with C.T. scan seems to be interesting in the management of hemoperitoneum with a moderate injury severity score and stable arterial and venous pressures. Three patients were recently managed non operatively with good results. The authors draw up these three cases with inclusion criterias and limits of the method. PMID- 1894700 TI - [Aorto-enteric fistulas. Report of 12 cases]. AB - Aorto-enteric fistulae are primary or secondary. The primary variant is the rupture of an aortic aneurysm into the gastro-intestinal tract. The secondary fistulae are complications of reconstructive aortic surgery. We report our experience with 12 aorto-enteric fistulae (2 primary and 10 secondary) treated from 1971 to 1989. All patients presented with gastro-intestinal bleeding and the fistula was to the duodenum (3), jejunum (8) or appendix (1). In the secondary patients, a mean of 5 years had elapsed since the aortic replacement. In addition to closure of the enteric defect, three types of treatment were applied: excision of the old prosthesis, infrarenal aortic closure and axillo-bifemoral bypass (5); insertion of a new graft (3) and local repair (3). A patient was not treated due to a triple carcinoma. Hospital mortality was 50%. We conclude that the diagnosis of aortoenteric fistula is difficult and that the mortality is high. The operative management remains imperfect and a subject of controversy. Prevention and early detection request more attention than in the past. PMID- 1894701 TI - [Injuries of the colon and emergency surgery]. AB - Tough less frequent that small bowel lesions, injuries and contusions of the colon rank second among the lesions sustained by hollow organs. They can be differentiated into contusions due to pressure in persons with multiple injuries, and penetrating wounds caused by blades or firearms. Although the latter involve multiple sites, they are most often clearly delineated and can be immediately and completely repaired, whereas contusions account for more severe parietal lesions, which sometimes require temporary bypass. The poor reliability of plain radiographs enables clinical investigations to recover an importance they seemed to have lost. Mortality has become very low in younger subjects, but it remains high after 60 years of age, and depends directly on the extent of peritoneal sepsis and on the associated deficiencies. PMID- 1894702 TI - [Intestinal obstruction caused by Meckel's diverticulum in adults]. AB - The diagnosis of intestinal obstruction caused by Meckel's diverticulum is difficult. The clinical evolution of the condition is subacute, with painful bouts occurring over several years and puzzling the clinicians. As a first step, explorative laparotomy solves the problem. Two cases show how difficult this decision is. Celioscopic surgery may be chosen in the future. PMID- 1894703 TI - [Immediate examinations in cancerology]. PMID- 1894704 TI - [What surgeons expect from immediate examinations in breast pathology]. PMID- 1894705 TI - [Surgeons and immediate examinations of lymph nodes. Practical modalities, diagnostic value and therapeutic consequences]. PMID- 1894706 TI - [Immediate histological studies in digestive tract surgery. The surgeon's point of view]. PMID- 1894707 TI - [Immediate anatomopathological examinations in private practice]. PMID- 1894708 TI - [Medico-legal problems of immediate examinations]. PMID- 1894709 TI - [Metastatic jejunal perforation of cancer of the larynx]. PMID- 1894710 TI - [Radiologic-surgical treatment of cancer of the rectum]. PMID- 1894711 TI - And don't go near the water. PMID- 1894712 TI - Piriformis as leg pain cause. PMID- 1894713 TI - Syncope after cardioversion. PMID- 1894714 TI - A bioenergeticist's revenge. PMID- 1894715 TI - The malignant consultation syndrome. PMID- 1894716 TI - Managing pulmonary embolism. AB - Although morbidity and mortality remain high, we now have effective strategies to prevent development of the disease in many patients at risk. For those who do not benefit from prophylaxis, our understanding of optimal diagnostic strategy has improved, as has that of classic anticoagulation therapy with heparin and warfarin. Thrombolysis may also improve outcome. PMID- 1894717 TI - Chronic nonspherocytic hemolytic anemia and G6PD deficiency. PMID- 1894718 TI - Peripheral circulatory response in cardiac failure. AB - Derangements of the peripheral circulation play a major role in the pathophysiology of congestive heart failure. Their appearance coincides with that of the symptoms and signs that characterize the full-blown clinical syndrome. Long-term therapy with ACE inhibitors partially reverses these abnormalities, but the pathologic mechanisms are still poorly understood. PMID- 1894719 TI - Cocaine heart disease. AB - Unlike neurologic toxicity, myocardial infarction appears to be an idiosyncratic response to the drug, unrelated to dose, duration of use, or route of administration. There is no marker to identify the person who may have life threatening cardiac effects after taking cocaine, but those who experienced myocardial ischemia once are at risk of recurrence if they use the drug again. PMID- 1894720 TI - Evaluation of displacement chromatography for the recovery of lactate dehydrogenase from beef heart under scale-up conditions. AB - A complex mixture of proteins was subjected to displacement development from a Tris Acryl DEAE anion-exchange column. Lactate dehydrogenase was used as the target protein in the evaluation of the resolution and separation under scale-up conditions. The conditions of operation were scaled up in terms of column size and protein load. Column length was found to play an important role in resolving the mixture. The performance of the displacement mode run was compared with a conventional ion-exchange elution run in terms of fraction purity and specific activities. In general, displacement chromatography of the complex mixture yielded better results. PMID- 1894721 TI - Determination of resin and fatty acids in sediments near pulp mill locations. AB - A gas chromatographic method for the determination of resin and fatty acids in sediments is described. In this procedure, the sediment sample was air-dried and soxhlet-extracted with a mixture of acetone--methanol (88:12, v/v) in the presence of hydrochloric acid. The acids extracted were converted into their pentafluorobenzyl esters and were then cleaned up on a deactivated silica gel column. Final analysis was performed on either a DB-17 or a DB-5 capillary column with electron-capture detection. Quantitative recovery was obtained from fortified sediments for all acids except palustric, neoabietic and levopimaric acids. The detection limit of all acids in this method was 0.1 micrograms/g based on 1 g of sample. This procedure has been successfully applied to the monitoring of resin and fatty acids in sediment samples collected in the vicinity of several Canadian pulp mill locations. PMID- 1894723 TI - Gas chromatographic system for the identification of halogenated pesticides by retention indices using n-alkanes as standards. AB - A gas chromatographic system for the evaluation of linear temperature-programmed retention indices allowing n-alkanes to be adopted as the reference retention markers for any type of analyte, irrespective of the atoms present in their molecules, is described. It is based on the simultaneous use of two different detectors (a flame ionization detector and a specific detector suitable for the sample components), both connected (in parallel) to the same column outlet. The performance of this system has been tested by measuring the retention indices of fifteen chlorinated pesticides under conditions of linear programming temperature, by adopting an electron-capture detector as the specific detector. The reliability of the retention indices thus determined has been proven by verifying that they can be reproduced under different chromatographic conditions. PMID- 1894722 TI - Determination of 19-nortestosterone, testosterone and trenbolone by gas chromatography-negative-ion mass spectrometry after formation of the pentafluorobenzylcarboxymethoxime-trimethylsilyl derivatives. AB - The known reaction of 3-ketosteroids with carboxymethoxylamine (to form the corresponding carboxymethoximes), followed by esterification of the carboxyl group with pentafluorobenzyl bromide, has been used to obtain derivatives of 19 nortestosterone, testosterone and trenbolone suitable for high-sensitivity detection with gas chromatography-negative-ion chemical ionization mass spectrometry. These derivatives, after further silylation of the alcoholic groups of the steroids, showed excellent chromatographic and spectrometric characteristics and were detectable in the low picogram range. The derivatization gave rise to the formation of two isomers which were distinguishable by gas chromatography. The existence of the two isomers was also confirmed by high performance liquid chromatography. Examples of the usefulness of this derivatization procedure are given for the analysis of 19-nortestosterone, testosterone and trenbolone in meat and urine samples. By the use of immunoaffinity extraction and addition of deuterated internal standards (synthesized by isotopic exchange), the new derivatization procedure allowed a correct identification and quantitation of the steroids and reached very low detection limits [0.02 ppb (10(9] for 19-nortestosterone and testosterone, 0.06 ppb for trenbolone]. PMID- 1894724 TI - Separation and determination of polyether carboxylic antibiotics from Streptomyces hygroscopicus NRRL B 1865 by thin-layer chromatography with flame ionization detection. AB - Thin-layer chromatography coupled with flame ionization detection was used to develop a method to separate and to determine simultaneously three polyether carboxylic ionophore antibiotics (abierixin, nigericin and grisorixin) produced by Streptomyces hygroscopicus NRRL B 1865. Various proportions of chloroform, methanol and formic acid (or acetic acid as a substitute for formic acid) were used in the developing solvent to determine changes in RF values of the antibiotics and to allow conditions for maximum resolution to be obtained. Development on Chromarods SII with chloroform-methanol-formic acid (97:4:0.6, v/v/v) gave satisfactory and reliable separations of the three polyether antibiotics. Under these conditions, the internal standard methyl desoxycholate was found to be suitable for their simultaneous determination in the lipid extracts of Streptomyces hygroscopicus NRRL B 1865. PMID- 1894725 TI - Purification to homogeneity of bovine prolactin by high-performance ion-exchange chromatography. AB - Homogeneous bovine prolactin (bPRL) has been obtained using a procedure based on high-performance anion-exchange chromatography. The procedure enables up to 6 mg of 99.4% pure bPRL to be obtained per hour, with a recovery of 32.4%. The purity of the protein was checked by N-terminal sequencing and sodium dodecyl sulphate polyacrylamide gel electrophoresis. The highly purified bPRL obtained with this method is suitable for complete structural and immunochemical studies. PMID- 1894726 TI - Enrichment of biologically active U1 small nuclear RNAs by ion-exchange high performance liquid chromatography. AB - The use of ion-exchange high-performance liquid chromatography in conjunction with preparative electrophoresis to facilitate the purification of biologically active snRNAs is described. Separation of total nuclear RNA from a Bombyx mori cell line was done with a Bio-Rad MA7 plasmid column in a HRLC 500 system. Individual fractions were subjected to electrophoresis through 14% polyacrylamide gels for identification. High levels of U1 RNA were confirmed by Northern analysis with a human U1 probe. Biological activity of RNAs from the column was demonstrated by their ability to incorporate 32P-AMP at the 3' end. Ion-exchange chromatography provides a rapid, automated method for purifying large amounts of RNAs that can then be utilized in further studies. PMID- 1894727 TI - Determination of phenoxyacid herbicides in water. AB - Novel clean-up techniques for a polymeric precolumn (PLRP-S) for the subsequent determination of bentazone and eight phenoxy acid herbicides in surface water samples are described. After preconcentration of the components at pH 3 on a 10 x 2 mm I.D. precolumn, the technique consists of a clean-up with 1000 microliters of 0.1 mol/l sodium hydroxide solution (pH 12.5) and of a heartcut consisting of four precolumn bed volumes of eluent directed to waste followed by ten precolumn bed volumes of eluent directed to the analytical column. Analytical separation is performed with acetonitrile-water (30:70) containing 0.005 mol/l of tetrabutylammonium hydrogensulphate (pH 8.3) (which is also the desorption eluent during heartcutting) on a polymeric analytical column (PLRP-S). With 25 ml of surface water, spiked at 0.25 and 1 microgram/l, applied to the precolumn, recoveries for all components were over 85% with a relative standard deviation (n = 5) of ca. 9% at 0.25 microgram/l and ca. 2% at 1 microgram/l. Detection limits in surface water samples are 0.05-0.1 microgram/l. Owing to automation, the total analysis time is ca. 30 min. PMID- 1894728 TI - Determination of diclofop-methyl and diclofop residues in soil and crops by gas chromatography. AB - A method is described for the determination of residues of the herbicide diclofop methyl and its metabolite, diclofop, in soil and crops. The residues were extracted with acetone-light petroleum and extracts were concentrated (diclofop was derivatized to its pentafluorobenzyl derivative), and then the products were purified on a chromatographic column containing alumina, silver-alumina and Florisil. Finally, they were determined by gas chromatography using an electron capture detector. The detection limits of diclofop-methyl and diclofop were between 0.01 and 0.05 mg/kg. The average recoveries were 76.4-97.2% and 72.8 105.2%, respectively, making the method suitable for statutory residue testing purposes. PMID- 1894729 TI - Lipophilic character of cardiac glycosides: correlation between RM values and acute toxicity data in different animal species. AB - The RM for a new series of cardiac glycosides were calculated by means of some of the delta RM values previously derived from another series of compounds. The experimental or calculated RM values of both series of derivatives were correlated with the acute toxicity data (log 1/C). The slopes of the linear equations for cats, dogs, guinea-pigs and frogs are very close, showing that the dependence of toxicity on the lipophilic character is the same in these animal species. PMID- 1894730 TI - Impaired immune responsiveness is an essential component in persistent central nervous system infection with gross murine leukemia virus. AB - Exposure of newborn mice to Gross murine leukemia virus (GMuLV) results in persistent viral infection of the central nervous system (CNS) white matter. Animals exposed to virus as neonates showed a marked depression in GMuLV-specific B lymphocyte function as evidenced by significant decreases in adult and neonatal anti-GMuLV antibody levels. Immunohistochemical analyses showed that the sites of GMuLV infection in the CNS were also devoid of major histocompatibility complex (MHC) class I and II protein expression, although transplantation of GMuLV infected brain tissue to the kidney capsules of immunocompetent mice induced a potent mononuclear cell graft infiltrate. These results indicate that persistent GMuLV infection of the CNS is linked to both impairment of anti-GMuLV peripheral immune responses and deficient antigen-presenting cell function within the CNS. PMID- 1894731 TI - Rat Schwann cells produce interleukin-1. AB - There is increasing evidence that Schwann cells of peripheral nerves may be able to function as accessory cells, interacting with the immune system in T cell mediated immune responses, by expression of the major histocompatibility complex (MHC) class II molecules. In addition to MHC class II-associated presentation of antigen to T lymphocytes, the release of a co-stimulatory factor, interleukin-1 (IL-1), is an essential function of accessory cells for T cell activation. In this study, we investigated if Schwann cells were able to produce IL-1. Purified cultures of neonatal and adult rat Schwann cells were incubated with various stimulatory agents. Supernatants and cell lysates were collected from these cultures and IL-1 activity was assayed. Both neonatal and adult rat Schwann cells produced IL-1 activity in response to bacterial antigens and the IL-1 activity was often higher in the cell lysate than in the supernatant. When stimulated neonatal or adult rat Schwann cells were examined with antibody against IL-1, strong immunolabelling was seen intracellularly, but no IL-1 was detected on the cell surface. Since IL-1 plays an important role in the initiation of immune responses, these observations support the view that Schwann cells may function as antigen-presenting cells, thereby taking part in neuroimmunological responses within peripheral nerves. PMID- 1894732 TI - Human glioblastoma cell derived transforming growth factor-beta 2: evidence for secretion of both high and low molecular weight biologically active forms. AB - Transforming growth factors beta (TGF-beta) form a family of multifunctional polypeptides which in the active dimeric forms have a molecular weight of 25 kDa. Human glioblastoma cells secrete immunosuppressive TGF-beta consisting mostly of TGF-beta 2 rather than TGF-beta 1. The results shown here demonstrate that in addition to the mature 25 kDa form of TGF-beta 2, glioblastoma cells release a biologically active high molecular weight form of TGF-beta 2 which suppresses the interleukin-2-dependent growth of a T helper cell line. The high and low molecular weight forms of TGF-beta 2, separated by polyacrylamide gel electrophoresis under non-reducing conditions, can be eluted from the gel retaining their immunosuppressive activity. Similar results were obtained when analyzing supernatants of Chinese hamster ovary (CHO) cells transfected with a cDNA for TGF-beta 2. Both the high molecular weight form (90-120 kDa) and the 25 kDa form can be immunoprecipitated with a monoclonal antibody against mature native TGF-beta 2 and are detectable in tumor cyst fluid from glioblastoma patients. Taken together, the data provide evidence that in addition to the well characterized 25 kDa form of TGF-beta 2 glioblastoma cells also secrete a high molecular weight form (90-120 kDa) with the biological characteristics of TGF beta 2. PMID- 1894733 TI - Association between glycoconjugate antibodies and Campylobacter infection in patients with Guillain-Barre syndrome. AB - In a retrospective study, we have analysed sera from a well-characterised Guillain-Barre syndrome (GBS) patient group for antibodies that react with gangliosides. Of 95 GBS patients and 85 control patients analysed, we found that 14 (15%) of GBS patients but only one control patient had antibodies that react with the gangliosides GM1 and/or GD1b but not GM2, GD1a and GT1b using a sensitive enzyme-linked immunosorbent assay (ELISA). This pattern of reactivity suggests binding to the carbohydrate structure Gal(beta 1-3)GalNAc which is shared between some glycolipids and glycoproteins. Similar antibodies have been found previously in a subpopulation of patients with lower motor neuron disease. In the present study, the predominant immunoglobulin class of these anti glycoconjugate antibodies was IgG rather than IgM. A correlation was found between the presence of these antibodies and prognosis in terms of disability at 3 and 12 months after presentation. Patients with anti-glycoconjugate antibodies also had a higher incidence of previous Campylobacter infections than the rest of the patient group, although the significance of this remains to be determined. PMID- 1894734 TI - Microglial cell-mediated anti-Candida activity: temperature, ions, protein kinase C as crucial elements. AB - An in vitro established microglial cell line, BV-2, constitutively exhibits high levels of anti-Candida activity. To elucidate the cascade of events leading to the accomplishment of such activity, we studied its dependence on temperature and ion availability. The role of protein kinases has also been studied by the specific inhibitors, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H7) and N-(2-guanidinoethyl)-5-isoquinoline sulfonamide hydrochloride (HA 1004). We found that (a) the BV-2 cell/Candida conjugate formation is a discrete step, temperature-, ion- and protein kinase-independent; (b) the phagocytic event, which is protein kinase-independent, is significantly impaired by temperature decrease and ion deprivation; (c) the fulfillment of anti Candida effects is strictly dependent upon temperature, ion availability and functional protein kinase. Functional protein kinase C, but not other kinases, is required for the accomplishment of anti-Candida activity, which, in fact, is selectively abrogated by H7 but not HA. Furthermore, protein kinase C activators, such as 12-O-tetradecanoylphorbol 13-acetate (TPA) or 1-oleoyl-2-acetyl glycerol (OAG), consistently potentiate BV-2 cell-mediated anti-Candida activity, the phenomena being dose-dependent. These results indicate that the multistep events leading a microglial cell to express anti-Candida activity can be dissected and differentiated for biochemical and biological demands, the latest along the cascade being the most demanding steps. PMID- 1894735 TI - Experiences in surgical repair of a totally avulsed scalp. AB - A case of total scalp avulsion is described in surgical detail. The neurovascular bundles remained nearly untouched on the surface of the galea aponeurotica. Only one frontal branch of the left temporal artery was found to serve as a nutrient vessel for the whole scalp. Three veins around the scalp circumference supplied the venous drainage. The right-dorsal part of the scalp underwent necrosis, obviously because of internal disruption on the capillary level. This area had to be skin-grafted secondarily. Mechanical aspects in respect of the neuro-vascular situation are discussed theoretically and some advice on the surgical approach is derived from our experience. PMID- 1894736 TI - Experience with AO reconstruction plates after partial mandibular resection involving its continuity. AB - A report is presented on experience with the use of 54 plates, without primary bone grafts, after resections for malignant tumours involving the continuity of the mandible, in 52 patients. There were complications in 27 cases: postoperative infection or soft tissue dehiscence occurred 20 times, chronic soft tissue perforation once, screw loosening twice, and plate fracture four times. Adjuvant radiotherapy and/or chemotherapy had no effect on the incidence of the complications. Seventeen of the plates (a good 30%) had to be removed prematurely due to the complications. Major deformity did not always occur if relative stabilization had developed through cicatrix formation. Thirty-seven plates (barely 70%) remained: in 19 cases until the death of the patient, in 3 cases until recurrence, in 12 cases until bone grafting, and in 3 cases they were still in situ up to 65 months. In principle, reconstruction plates have proven themselves. However, application and soft tissue coverage need great care and a great deal of experience. PMID- 1894737 TI - The use of miniplates in mandibular fractures. An in vitro study. AB - To test the stability of miniplate osteosynthesis in the mandible, a three dimensional in vitro model was developed. Four clinically relevant fracture situations were simulated by osteotomies in polyurethane mandibles. The stability of the osteosyntheses was tested according to a reproducible procedure of unilateral loading under conditions of static equilibrium. The mandible was supported at the condyles in silicon rubber fossae and was held in position by traction on the coronoid processes in combination with preloading in the region of the incisors with a force of 10 N. Six points were tested to register the effects of unilateral loading on bending and torsion at the sites of the osteotomies. The following results were obtained. The preliminary results show that in cases of jaw angle fracture neither bending nor torsional forces are sufficiently controlled by miniplate-fixation in the commonly proposed position. Furthermore, it was confirmed that fracture treatment in the canine region requires two plates instead of one to resist displacement of the fracture fragments during function. PMID- 1894738 TI - Traumatic luxation of the eyeball. AB - Traumatic injuries of the orbit may lead to luxation of the eyeball. This complication is of uncommon occurrence. Aetiology, clinical features, prognosis and treatment are discussed on the basis of the occurrence of the luxation of the eyeball in a 30-year-old man. PMID- 1894739 TI - Single-table autogenous calvarial grafting for cranioplasty. AB - We present data from 12 patients with cranial defects restored with single-table calvarial autografts which comprised the outer table of the calvarium and which were removed from the same area on the opposite of the skull vault or immediately adjacent to the cranial defect. Trauma (nine patients), congenital malformation (two patients) and operation (one patient) accounted for the cranial defects. The follow-up period has been 6 to 30 months. No bone resorption or infection occurred during that time. Only in two cases was there slight depression at the recipient site; no revision was necessary. PMID- 1894740 TI - Intra- and early postoperative complications of the Le Fort I osteotomy. A retrospective study on 410 cases. AB - The results of a retrospective study of the complications that occurred in 410 Le Fort I osteotomies performed in the Department of Oral and Maxillofacial Surgery of the Free University Hospital, Amsterdam, the Netherlands, are presented. The complication rate was 9.0%. In the discussion, our results are compared with the literature.--Suggestions are made on how to avoid these complications. PMID- 1894741 TI - Application of magnetic resonance imaging and ultrasonography to preoperative evaluation of masseteric hypertrophy. AB - A case of unilateral masseteric hypertrophy in a 30-year-old man is described. Preoperative evaluation was performed by magnetic resonance imaging (MRI), computed tomography (CT) and ultrasonography (USG). MRI could delineate not only the border between medial and lateral layers of the masseter but also delineate the hypertrophic portion. MRI also provided more information in respect of the masseter muscle as well as the other masticatory muscles and the surrounding tissues than CT. USG was useful because of its real-time processing, especially in this case where facial asymmetry was emphasized during mastication. We resected the medial lower-half of the masseter intraorally based on these imagings and obtained a successful result. PMID- 1894742 TI - Cathepsin B- and L-like activities at local gingival sites of chronic periodontitis patients. AB - The cysteine proteinases cathepsins B and L have the potential to degrade connective tissue in chronic periodontitis and this may progress episodically at individual tooth sites. The activities of cathepsin B- and L-like proteinases in homogenised gingival tissue from control and periodontitis patients were measured biochemically using the selective peptide substrate Z-Phe-Arg-AFC and the selective cathepsin L inhibitor Z-Phe-Phe-CHN2. Each tooth site was divided, where appropriate, into gingival tissue and granulomata. These were assayed separately and the measurements related to the DNA and protein contents of the tissues. Enzyme activity in healthy control tissue was significantly lower than in diseased tissue. Enzyme activity in gingival tissue and total tissue from periodontitis patients decreased with increasing pocket depth, clinical attachment level, gingival index and bleeding index whilst cathepsin B activity in granulomata increased with increasing pocket depth and clinical attachment level but not with increasing gingival index or gingival bleeding index. Mean enzyme activity in gingival tissue was 1.6-2.8 times greater than in granulomata. Mean patient enzyme activity in diseased patients did not correlate positively with their mean pocket depth, clinical attachment level, gingival index or gingival bleeding index. These results are best explained by the probable cellular origins of the enzymes and the likely influence of their serum and tissue inhibitors during the disease process. PMID- 1894743 TI - Sharpening of ultrasonic scalers. AB - Instruments suitable for removing calculus, plaque and necrotic cementum, which hinder normal periodontal reattachment, are extremely important for successful therapy. The test was carried out in order to see if a standard scaler used for ultrasonic tartar removal maintains its physical features when sharpened. 6 scalers, compatible with piezo-electric generators, were tested and 2 diameters, A and B, weights and resonance frequencies were measured. Scalers no. 2, 3, 4, 5, were sharpened and was used as control. All measurements were taken again at the end of the test. Statistical analysis reveals significant variations, after sharpening, of A diameter (t = 4.14 greater than 3.55, p less than 0.01), B diameter (t = 5.34 greater than 3.355, p less than 0.01) and resonance frequency (t = 2.82 greater than 2.306, p less than 0.05); in contrast, there is no significant change of weights (t = 1.17 less than 2.306, p greater than 0.05). These results suggest that sharpening slightly modifies the physical features of ultrasonic tips, so that sharpening ultrasonic scalers, from a physical point of view, can be carried out, paying attention not to damage the water cooling system. PMID- 1894744 TI - Cell populations and episodic periodontal attachment loss in humans. AB - The purpose of the present study was to assess possible associations between episodic probing attachment loss and cell populations in the supracrestal connective tissue in humans. 10 systemically healthy adult patients with untreated advanced periodontitis were monitored during a period of 10 months. At baseline and every month thereafter, probing attachment levels were measured at 6 sites of every tooth using an electronic pressure sensitive probe and flexible stents. Corresponding contralateral sites were identified where 1 site had lost 2 mm or more attachment within the previous month (P), and the other site had not (C). Supracrestal soft tissue biopsies were taken from these sites, processed and cut into 1 micron sections. Cell populations were identified in superficial and deep connective tissue areas by counting fibroblasts, macrophages, plasma cells, mast cells, granulocytes, lymphocytes, endothelial cells and the total number of inflammatory cells. Analysis of variance assessed differences in cell populations between P- and C-sites. There were statistically significantly higher numbers of fibroblasts in the standard areas of C-sites (p less than 0.0001). In P-sites, the numbers of macrophages, plasma cells, mast cells, lymphocytes and total inflammatory cells were significantly higher as compared to C-sites (p = 0.05 0.0001). There were no differences in cell populations between superficial and deep connective tissue areas within P- and C-sites (p greater than 0.2). Clinically assessed episodes of periodontal disease progression may be associated with site-specific shifts in inflammatory cell populations. PMID- 1894745 TI - Marking width, calibration from tip and tine diameter of periodontal probes. AB - The present study comprises an investigation of 7 different probe types, representing currently-marketed major designs (WHO-CPITN, Williams, Michigan), as well as available calibration systems (engraved, etched and painted markings). Width of markings, accuracy of calibration from probe tip, and tine diameter at the tip and at specified points along the tine were assessed, using a stereomicroscope at a magnification of x 40. Blind duplicate measurements of these probe tine characteristics were 100% reproducible to within 0.01 mm. There was an overall range in marking width from 0.00-1.13 mm. The best marking, in that it had no appreciable width and the highest accuracy, was the discrete transition between normal and engraved parts of probes with engraved bands. Mean inaccuracies of different probe sets varied from 0.06 to 0.22 mm. Probes from the same batch from the same production line could differ by more than 0.5 mm in calibration. Mean tip diameter ranged from 0.28 to 0.70 mm. It was concluded that probe tine diameter and calibration should be considered in addition to other variables of periodontal probing. Standardisation of tine characteristics and avoidance of the use of different types or batches in a single study should enhance the accuracy and reproducibility of periodontal probe-dependent measurements. PMID- 1894746 TI - Autotransplantation of third molars as treatment in advanced periodontal disease. AB - The aim of this study was to investigate the prognosis of replacing molars with advanced periodontitis by autotransplanted fully developed third molars. The patient sample consisted of 18 subjects, 24-58 years of age. The patients selected had at least 1 molar with advanced periodontal tissue destruction. After extraction of the diseased molar, autotransplantation of a third molar was immediately performed. After a splinting and healing period of 2-3 weeks, endodontic treatment was carried out. The follow-up included recordings of the clinical parameters, probing periodontal pocket depth, probing attachment level, percussion sound, and mobility. Radiographs were taken immediately after the surgical procedure, after 6 months, 1 year, and thereafter annually. The results of this study indicate that autotransplantation may be an alternative treatment procedure for molars with advanced periodontal disease. PMID- 1894747 TI - Prevalence of juvenile periodontitis in Chile. AB - The aim of this survey was to study the prevalence of juvenile periodontitis in schoolchildren aged 15-19 years in Santiago, Chile. A random sample of 2500 schoolchildren (1318 male, 1182 female) that represented the full range of different socio-economic strata and ethnic groups seen in the population of Santiago, was used. Initially, the children were screened clinically at school by assessment of probing depths around the incisors and first molars with a WHO 621 pattern probe. Children with 2 or more teeth with 5.5 mm or deeper pockets were invited for a radiographic examination comprising bitewing radiographs of molars, and periapical radiographs of incisors. Any subject with 2 mm or more alveolar bone loss was invited for a full clinical and radiographic examination. After screening, 27 subjects had a tentative diagnosis of juvenile periodontitis. 4 of these refused radiographic examination and only accepted a thorough clinical examination. 23 subjects presented themselves for the radiographic and complete clinical examination. Of the 27 subjects selected for detailed examination, 8 subjects (7 female, and 1 male) were diagnosed as having juvenile periodontitis. There was an overall prevalence of juvenile periodontitis of 0.32% with 95% confidence, which gives a range of +/- 0.10%. When prevalence was assessed by socio-economic status, juvenile periodontitis was found more commonly in low socio-economic group. The results of the current study suggest that in Chile, there might be a relationship between socio-economic status and prevalence of juvenile periodontitis, and that this disease is more frequent in women. PMID- 1894748 TI - Histologic studies on the extension of the inflammatory infiltrate in human periodontitis. AB - This study was undertaken to re-examine early and recent morphologic descriptions of gingival and periodontal inflammation based on a study of gingival biopsies and block sections of human jaws. A collection of 350 autopsy and surgically retrieved jaw sections containing multiple teeth and displaying various stages of periodontal inflammation were subjected to routine histologic preparation and analyzed with step serial sections. 105 gingival biopsies, serially sectioned, including 15 clinically normal specimens, were also studied. The results of these investigations suggest that the inflammatory lesion extends into the alveolar process and elicits a response, often before evidence of crestal resorption or connective tissue attachment loss has occurred. Similarly, deep penetrations of inflammatory cells into the alveolar bone, periodontal ligament and periapical tissues, along with fibrosis and enlargement of the marrow spaces, were common findings with advancing disease. More widespread distributions of inflammatory cells than previously described were found in clinically normal gingiva, while in more inflamed gingiva, the inflammatory cell types found and their pattern of distribution varied greatly from individual to individual. These observations cast doubt on the perception of human periodontitis as a localized and marginal disease and suggest that its effects may be much more pervasive than previously thought. PMID- 1894749 TI - Healing of sites within the dog periodontal ligament after application of cold to the periodontal attachment apparatus. AB - The potential of periodontal ligament-derived tissues to regenerate periodontal attachment after cryosurgical trauma to the PDL in dogs was evaluated. The buccal alveolar plate of each canine tooth was exposed by a semi-lunar excision. A 3 mm thick cryoprobe, cooled to -81 degrees C, was placed on the bone 5 mm apical to the crest for 10 s. This induced cellular devitalization in the bone directly in contact with the probe and the PDL under it. The freezing-thawing cycle was repeated 3 times. Control sites were sham-operated at room temperature. Histologic sections from the center of the lesions were obtained from 1 h, 48 h and 30 d specimens. 1-h control and experimental histologic sections were similar. At 48 h post-surgery, the cellular component of the frozen PDL could not be identified and inflammatory response was minimal. The collagenous framework, however, appeared to form a continuum between the alveolar bone and cementum. Lacunae in the bone at the frozen segment were empty. The injured PDL was surrounded by normal PDL. Control specimens appeared normal. At 30 d, the PDL space in the frozen segments was populated by PDL-like tissue which did not differ significantly from the PDL coronal or apical to it. Collagen fibers appeared to be attached to the cementum on one side and to the alveolar bone on the other. Bone resorption or ankylosis was not observed in the experimental sites. It is suggested that the extracellular matrix in the devitalized area was preserved, supporting regeneration of the cryolesion. PMID- 1894750 TI - Levels of interleukin 1 beta in tissue from sites of active periodontal disease. AB - Interleukin 1 beta is a potent bone resorptive cytokine which also mediates soft tissue destruction through the stimulation of prostaglandin production, and the induction of collagenase and other proteases. This constellation of activities suggests a role for IL-1 beta in the pathogenesis of human periodontitis. Levels of IL-1 beta were therefore determined in tissue obtained from (1) diseased, active (2) diseased, inactive and (3) healthy sites from 12 patients with destructive adult periodontitis. Disease activity was defined as attachment loss of greater than or equal to 2.5 mm, as determined by sequential probing and the tolerance method. IL-1 beta was extracted from homogenates of tissue biopsies taken at surgery, and levels were quantified by ELISA. IL-1 beta was found to be present in most patient tissue samples, with levels ranging from 0-82 ng/ml. Disease active sites had higher IL-1 beta levels (p less than 0.05) than inactive and healthy sites. Diseased inactive sites were divided into 2 groups, those losing small amounts of attachment (0.5-2.0 mm, worsening sites) and those which showed no change or attachment gain (stable sites). Stable diseased sites had IL 1 beta levels which were comparable to those found in healthy sites, and which were significantly different from active sites (p less than 0.02). Worsening sites had IL-1 beta levels intermediate between the levels in stable and active sites. Detection of disease activity occurred more frequently at sites with IL-1 beta levels greater than 25 ng/ml (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1894751 TI - Associations between subgingival plaque bacterial morphotypes and clinical indices? AB - The aim of the present study was to evaluate possible associations between subgingival plaque bacterial morphotypes, as assessed by darkground microscopy, and clinical indices of routine adult chronic periodontitis. Clinical indices were plaque index (PlI), gingival index (GI), sulcus bleeding index (SBI), papilla bleeding index (PBI), attachment loss (AL), pocket depth (PD) and probeable pocket depth (PPD). Apical border plaque was sampled in vivo and after extraction to test whether direct or indirect sampling affected any such associations. Similarly, pocket depth and attachment loss were also assessed directly and indirectly on the same teeth, in vivo or after extraction. The influence of the type of index used to record inflammation (GI, SBI, PBI) was also assessed, as were the effects of the numbers of sampled subjects and the method of analysis, which comprised the use of transformed and untransformed data and of parametric and non-parametric tests. Data were collected in relation to the approximal surfaces of 44 teeth extracted from 22 adults (2 teeth each) and from 1 pair of contralateral upper anterior or premolar teeth in each of 100 adults, all which untreated routine chronic periodontitis. Selected subjects had greater than or equal to 4 mm probeable pocket depth and/or attachment loss, and radiographic evidence of bone loss in relation to 1 approximal surface on each of 1 pair of contralateral anterior or premolar teeth, or to 2 teeth scheduled for extraction. Plaque preparation and darkground microscopy were as described previously. Insignificant associations (p greater than 0.05) were demonstrated between supragingival plaque (PlI) and periodontal inflammation (GI, SBI, PBI) or destruction (PPD and AL), as well as between inflammation and attachment level. In contrast, significant moderate associations (r = 0.5-0.77) were demonstrated between each of the 3 morphotype groups; spirochaetes, other motiles and cocci. Spirochaetes showed a significant moderate (r = 0.5) positive association with pocket depth with a 2.43% mean increase of spirochaetes for each 1 mm increase of PPD. Although highly significant associations (r = 0.9) were demonstrable between the 3 inflammation indices (GI, SBI, PBI) themselves, only PBI showed significant positive associations (r = 0.3) with spirochaetes and other motiles. Also, PlI showed significant associations with each of the 4 morphotypes (r = 0.3-0.5). The heterogeneity of spirochaetes and other motiles as well as the multiplicity of possible aetiological microbial agents in plaque may have resulted in underestimated associations between subjects as well as undetectable association within a given mouth using only 4 morphotype groups.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1894753 TI - Drug development and patient benefit. PMID- 1894752 TI - Citric acid treatment of periodontitis-affected cementum. A scanning electron microscopic study. AB - Previous studies have described an inconsistent histological occurrence of a zone of surface demineralization on periodontitis-affected cementum following treatment with citric acid, and a lack of connective tissue attachment to the latter surfaces. In view of these findings, the purpose of the present study was to use scanning electron microscopy to examine the surface morphology of cementum from normal and periodontitis-affected root surfaces following citric acid treatment for differences in the effects of the demineralizing solution on these surfaces. Cementum surfaces were derived from the roots of extracted human teeth from areas beneath attached periodontal ligament fibers (normal) and calculus deposits (periodontitis-affected). 5 specimens were evaluated in both groups. Periodontal ligament fibers were removed from normal root surfaces with a curette, and calculus deposits were removed from periodontitis-affected root surfaces using an ultrasonic scaler. The resultant 5 specimens in each group were then sectioned in half, one-half serving as the untreated control and the other as the experimental, citric acid treated specimen. Experimental specimens were immersed in a saturated solution of citric acid, pH 1 for 3 min and then rinsed in tap water. Both control and experimental specimens were dehydrated in ethanol, critical-point dried, sputter-coated with gold and examined in the scanning electron microscope for morphological characteristics. Citric acid treatment of cementum from normal root surfaces produced an undulating, markedly fibrillar surface morphology which is consistent with the exposure of a fibrillar, collagen substrate. Periodontitis-affected cementum, however, was not appreciably altered in appearance by the citric acid treatment, having only a faint mat-like surface texture. (ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1894754 TI - Nonsteroidal anti-inflammatory drugs: effects on kidney function. AB - Nonsteroidal anti-inflammatory drugs (NSAIDs) are capable of inducing a variety of renal function abnormalities, particularly in high-risk patients with decreased renal blood perfusion who depend on prostaglandin synthesis to maintain normal renal function. Fluid retention is the most common NSAID-related renal complication, occurring to some degree in virtually all exposed individuals; however, clinically detectable edema occurs in less than 5% of patients and is readily reversible on discontinuation of the NSAID. Other electrolyte complications, notably hyperkalemia, are seen infrequently and occur in specific at-risk patients. The next most worrisome complication is acute deterioration of renal function, which occurs in high-risk patients and is also reversible. Nephrotic syndrome with interstitial nephritis is a rare problem of NSAID use and is reversible. Papillary necrosis is the only permanent complication of NSAIDs and is very rare. Altogether, these renal function abnormalities, with the exception of mild fluid retention, are clinically detectable in approximately 1% of exposed patients. Given the number of patients who take NSAIDs on a prescription or over-the-counter basis, the absolute number of at-risk patients is relatively large. Consequently, an appreciation for the risk factors and pathophysiology of NSAID-induced renal function abnormalities is required for optimal use of these drugs. PMID- 1894755 TI - Clinical pharmacology education in a division of cardiology. AB - A working model of how clinical pharmacology education can be interwoven into the matrix of an academic cardiology program that includes didactic teaching, clinical research, and patient care has been presented. Essential to the success of such a program is the commitment and dedication of both its full-time and voluntary faculty. Moreover, a comprehensive plan of organization and allocation of efforts is vital to the success of such a complex undertaking. As we look to the future, the discipline of clinical pharmacology will be increasingly relevant to the practicing cardiologist. PMID- 1894756 TI - The effect of pirmenol administration on the anti-coagulant activity of warfarin. AB - The effect of administration of pirmenol, an extensively metabolized and plasma protein-bound antiarrhythmic agent, was evaluated in ten patients on chronic warfarin therapy. After a 3-week baseline period and 7 days of placebo administration, patients received 150 mg of oral pirmenol every 12 hours for 14 days. Prothrombin time was determined during the baseline and placebo periods, during pirmenol administration, and 14 days after the last pirmenol dose (washout). There was no significant difference between mean baseline, placebo, pirmenol, and washout prothrombin times. Coadministration of pirmenol does not appear to affect the anticoagulant activity of warfarin. PMID- 1894757 TI - The effect of tobramycin on the renal handling of vancomycin. AB - Studies in experimental animals and humans have suggested that enhanced renal and auditory toxicity occur with concurrent vancomycin and aminoglycoside treatment. In volunteers, systemic vancomycin clearance at steady-state was measured simultaneously with renal clearances of vancomycin, creatinine, inulin, and para aminohippurate. Group 1 (n = 9) received vancomycin 5 mg/kg IV for 1 hour, then 1.1 mg/kg/hr for 3 hours. Group II (n = 7) received vancomycin plus tobramycin (2 mg/kg IV over 30 min). Groups did not differ demographically. Audiograms were obtained before and after vancomycin. Plasma samples were collected serially for vancomycin and tobramycin pharmacokinetic studies. Serum concentration versus time data were fit to a two-compartment model for vancomycin and a one compartment model for tobramycin. For all volunteers, creatinine, inulin and para aminohippurate clearance, and audiograms were not altered from baseline and were not statistically different between groups. No significant effect of tobramycin on vancomycin pharmacokinetics was observed. conversely, vancomycin had no significant effect on tobramycin pharmacokinetics. The nephrotoxic synergism of vancomycin and tobramycin is not explained by short-term differences in renal handling. PMID- 1894758 TI - Dose-dependent response to phenylpropanolamine: inhibition of orthostasis. AB - Phenylpropanolamine, a widely consumed over-the-counter drug, is known to elevate blood pressure, but the mechanism is unknown; it may be both a direct and indirect sympathomimetic. This study investigated the effects of 75-mg sustained release phenylpropanolamine, 75-mg phenylpropanolamine plus 400-mg caffeine, and 150-mg phenylpropanolamine on blood pressure, plasma norepinephrine, and epinephrine levels in 16 normotensive subjects in a double-blind, placebo controlled crossover design. Mean peak phenylpropanolamine levels of 317 +/- 26, 152 +/- 17, and 157 +/- 17 ng/mL for 150-mg phenylpropanolamine, 75-mg phenylpropanolamine, and 75-mg phenylpropanolamine plus 400-mg caffeine, respectively, were reached at about 3.6 hours after dosing. The maximal increases in supine diastolic blood pressures after all three phenylpropanolamine containing drugs were almost three times that after placebo (P less than .05), but peak blood pressures occurred at about 2.3 hours earlier than peak phenylpropanolamine levels. Blood pressure increases correlated with phenylpropanolamine plasma levels (r = .49 for systolic blood pressure and r = .34 for diastolic blood pressure; P less than .0001 for both). Norepinephrine levels increased after the administration of 150-mg phenylpropanolamine and 75-mg phenylpropanolamine plus 400-mg caffeine; norepinephrine increases correlated with phenylpropanolamine levels (r = .34, P less than .0001). The expected increment in norepinephrine induced by standing was significantly decreased by phenylpropanolamine in a dose-dependent mode. The study supports the idea that phenylpropanolamine as both a direct (at alpha -1 and alpha-2 receptors) and an indirect sympathomimetic agent. PMID- 1894759 TI - Comparison of the effect of isosorbide-5-mononitrate and isosorbide dinitrate in a slow-release form on exercise-induced myocardial ischemia. AB - A randomized, double blind, placebo-controlled crossover study on 20 patients with exercise-induced angina pectoris and reproducible ST-segment depression during exercise-stress test was performed to compare the effect of a single dose of 120 mg of isosorbide dinitrate in a slow-release form with that of a twice daily application of 20 mg of isosorbide-5-mononitrate. Symptom-limited exercise tests were done, and nitrate plasma levels were measured in the subjects 6, 10, and 24 hours after the first administration of the drug. Both drugs produced a highly significant reduction in the size of exercise-induced ST-depressions (P less than .001) 6 and 10 hours after the first administration of isosorbide dinitrate as well as 6 hours after the first and 4 hours after the second dose of isosorbide-5-mononitrate. The effect was still significant (P less than .05) 24 hours after the administration of isosorbide dinitrate in a slow-release form and 18 hours after the second dose of isosorbide-5-mononitrate. In the case of the drug isosorbide dinitrate, nitrate plasma levels for its metabolite, isosorbide-5 mononitrate, were highest 10 hours after first application. In the case of the drug isosorbide-5-mononitrate, nitrate plasma levels were highest 4 hours after the second dose. Two 20 mg doses of isosorbide-5-mononitrate and a single dose of 120 mg isosorbide dinitrate in a slow release form have a comparable effect on the reduction of exercise-induced ST-segment depressions. PMID- 1894760 TI - Nicotinic acid for the treatment of hyperlipoproteinemia. AB - Nicotinic acid is a water-soluble B-complex vitamin that has been shown, in high doses, to lower total plasma cholesterol (C), LDL-C, and VLDL-triglycerides (Tg), while raising HDL-C in patients with type II, III, IV, and V hyperlipoproteinemia. Its exact mechanism of action is not known, but it appears to lower the production of VLDL in the liver while activating lipoprotein lipase. The drug may also influence the metabolism of HDL-C. The drug is a second or third choice for isolated hypercholesterolemia because of a high incidence of side effects. However, it has a therapeutic advantage as a monotherapy when reduction of both LDL-C and triglycerides are needed in patients with severe combined hyperlipidemia. The drug can be used in combination with other cholesterol-lowering agents to maximize lipid-lowering activity. Nicotinic acid has been associated with a reduced risk of cardiovascular morbidity in clinical trials. PMID- 1894761 TI - Decreased systemic clearance of lorazepam in humans with spinal cord injury. AB - Serum concentration-time course profiles, serum protein binding, and disposition parameters of lorazepam (LRZ), a benzodiazepine with sedative-hypnotic, anxiolytic, and anti-seizure properties, were studied as part of a systematic effort to define population-specific pharmacokinetic behavior in humans with chronic spinal cord injury (SCI). Twenty-four healthy subjects (nine tetraplegic, six paraplegic, nine able-bodied) were given an IV bolus of 2.0 mg of LRZ. Noncompartmental estimation of pharmacokinetic parameters disclosed a 37% decrease in the total systemic clearance (CL) of LRZ in tetraplegic patients. Altered LRZ clearance was observed independently of significant changes in volume of distribution or serum protein binding. The early elimination of LRZ (0-10 hr) was characterized by wide fluctuations in serum concentration suggestive of impaired enterohepatic circulation and could be distinguished from LRZ elimination observed in able-bodied subjects. We conclude that decreased systemic CL and the altered terminal elimination profile of LRZ are attributable to the pathophysiology of SCI. PMID- 1894762 TI - Drug dose prediction with flexible test doses. AB - This article presents the first known practical method to apply one-compartment pharmacokinetic modeling to prediction of doses for drugs from one or more blood drug concentrations, without requiring approximations or a computer. It should be useful for regulating doses of orally administered CNS drugs whose effects develop over a day or more, e.g., lithium, antidepressants, and anticonvulsants. Pharmacokinetic calculations for sequences of one, two, and three test doses are condensed into graphs that can be rapidly applied for clinical purposes. These graphs account for dose division, blood sampling time, and drug elimination rate; they show that the ratio of the steady-state day-mean drug level to the test-drug blood level is independent of the half-life if the test level is about a day after the last test dose. The calculations show the same value as experimental measurements for the ratio between steady-state serum lithium level and serum lithium level measured after a test dose. A rational strategy for drug-loading doses is discussed. PMID- 1894763 TI - Theophylline pharmacokinetics: effect of continuous versus intermittent cimetidine i.v. infusion. AB - The comparative effects of continuous versus intermittent cimetidine infusion on theophylline pharmacokinetics were evaluated in 12 nonsmoking healthy male volunteers. Each subject received aminophylline 0.9 mg/kg/hr over 6 hours alone (control) and in random order at 1 week intervals, in combination with intermittent cimetidine (300 mg IV over 15 minutes every 6 hours) and continuous cimetidine (50 mg/hr IV) infusions. Both cimetidine regimens were administered for a total of 50 hours. Serial plasma samples were obtained and assayed for theophylline by HPLC. No significant differences existed in mean theophylline clearance and mean volume of distribution among control, intermittent or continuous cimetidine regimens; the power was greater than 80% to detect a 30% change in clearance. Only a minor difference in theophylline half-life between control and continuous cimetidine infusion (7.59 +/- 2.52 vs. 9.05 +/- 3.17 hr; P less than .05) was observed. These findings do not support a clinically significant interaction between IV aminophylline and cimetidine administered IV either as a low dose continuous infusion or as an intermittent infusion. PMID- 1894764 TI - Validity of self-reports of caffeine use. AB - The relationship between self-reports of caffeine ingestion on two occasions and measured plasma concentrations of caffeine and its major metabolites was examined. A subject population [25 men and 25 women, age 20-45 years (mean: 28.7 yr)] that was enrolled in a benzodiazepine pharmacokinetic study underwent general medical screening on two occasions, each including detailed caffeine histories. Before beginning their scheduled study, plasma samples were obtained and evaluated by HPLC for caffeine, paraxanthine, theophylline, and theobromine. These values were compared with estimates of caffeine consumption in mg/day generated from both histories. There was no significant difference between plasma levels of caffeine, metabolites, or caffeine plus metabolites for categories corresponding to reports of low, intermediate or high caffeine use. A self reported caffeine consumption of greater than 300 mg/day (high) did correlate, however, with a significant smoking history. The authors conclude that self reports of caffeine ingestion do not accurately reflect acute exposure, and that if caffeine use is of importance in a given setting, reports should be confirmed by biochemical means. PMID- 1894765 TI - Postnatal development of thalamic recipient neurons in the monkey striate cortex: I. Comparison of spine acquisition and dendritic growth of layer 4C alpha and beta spiny stellate neurons. AB - A quantitative study has been made from Golgi impregnations of the maturation of dendrites and their spines on spiny stellate neurons in the macaque monkey primary visual cortex. The neurons studied lay within either the alpha or the beta division of lamina 4C; previous workers have shown the alpha division neurons to be contacted by thalamic axon terminals arising from the magnocellular division of the lateral geniculate nucleus (LGN) of the thalamus and the beta division neurons to be contacted by parvocellular LGN inputs. Most thalamic terminals and perhaps the majority of other type 1 (Colonnier, '81), presumed excitatory, inputs to these cells make synaptic contacts on the tips of their dendritic spines. Measurement was made of relative changes in the total number of spines on these alpha and beta spiny neurons over age by measuring both spine density along the dendrites and dendritic arbor size in single 90-microns sections from Golgi rapid preparations. Our previous work (Lund et al., '77; Boothe et al., '79) showed a marked proliferation and attrition of spines and dendritic branches to occur in the early postnatal weeks; Rakic et al. ('86) have since proposed that there is a cortexwide synchrony of synapse acquisition and loss during this same period. However, different visual capacities channelled via the magnocellular and parvicellular geniculate relays show different maturational rates (Harwerth et al., '86). This study indicates that the anatomical maturation of spines on the alpha and beta neurons is not temporally coincident from birth to 30 weeks. During this period, phases of spine acquisition and loss on alpha neurons precedes similar phases on beta neurons. The alpha neurons carry a peak spine population at 5-8 weeks postnatal, whereas the beta neurons carry their peak spine populations between 8 and 24 weeks postnatal. At all ages prior to 30 weeks, the two sets of neurons carry quite different total spine populations. Close to 30 weeks of age, the total spine coverage has fallen on both sets of neurons and becomes identical between the alpha and beta neurons. In animals aged 30 weeks to adult, spine coverage per neuron is maintained at a common figure for the alpha and beta neurons despite further growth and disparate dendritic arbor sizes and different local spine densities in the two groups; this suggests that some common sampling paradigm between pre- and postsynaptic elements is adopted by the alpha and beta neurons and also suggests the development of a close functional correlation between the two sets of neurons. PMID- 1894766 TI - Postnatal development of thalamic recipient neurons in the monkey striate cortex: II. Influence of afferent driving on spine acquisition and dendritic growth of layer 4C spiny stellate neurons. AB - This study uses Golgi-impregnated material to examine the effects of altering the nature of afferent driving on the maturation of spines and dendrites on thalamic recipient spiny stellate neurons in layers 4C alpha and beta of the monkey striate cortex. These two laminae receive input from different sets of thalamic afferents with different functional properties. The development of dendritic spine and dendritic branch populations on these neurons in experimental animals is compared to the same features on similar groups of neurons in a series of normal animals described in the preceding study (Lund and Holbach, '91). Three conditions of rearing were used to alter afferent driving from normal: complete darkness (with in some cases return to normal diurnal light-dark cycle), bilateral eye lid suture, and monocular eye lid suture. Some of the normal and dark-reared infant monkeys were examined behaviorally for visual capacity in an earlier study (Regal et al., '76). All conditions of abnormal afferent driving caused changes from the normal developmental patterns of spine and dendritic arbor growth in these first-order neurons of the cortex and each condition differed in the nature of change produced. Major findings of this study are: 1. Vigorous spine acquisition and dendritic growth occurs under all conditions of visual deprivation on alpha and beta neurons. Eventual spine and dendritic attrition occurs under at least conditions of bilateral or monocular lid suture to produce a rather constant adult morphology. We assume, therefore, that visually driven activity is a modulator or shaper of the developmental process for thalamic recipient neurons of visual cortex, rather than being an initiator, terminator, or driving force for their maturation. 2. An innate "clock," whose nature is unknown but is apparently not driven by visual input, initiates and terminates a period of growth of the thalamic recipient neurons between birth and 30-32 weeks of age. 3. Factors controlling dendritic arbor growth and retraction are different from those controlling spine synapse addition or attrition. 4. Whereas the alpha and beta neurons normally show quite different early growth patterns between birth and 30 weeks of age, when both eyes are simultaneously deprived of vision, an early temporal and numerical convergence occurs in patterns of spine population development on the two groups of neurons. This convergent pattern assumes a different form in dark-reared and lid-sutured animals.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1894767 TI - Postnatal development of thalamic recipient neurons in the monkey striate cortex: III. Somatic inhibitory synapse acquisition by spiny stellate neurons of layer 4C. AB - The development of type 2 (Colonnier, '81) synapses on the cell bodies of thalamic recipient spiny stellate neurons in layers 4C alpha and 4C beta of primary visual cortex neurons was examined over the first 36 postnatal weeks and in the adult monkey. The type 2 synapses, known to be GABAergic (Ribak, '78) and therefore presumed to be inhibitory, developed faster on the alpha neurons than the beta neurons. Both neuron groups show a marked increase and then decline in the percentage of the somatic membrane covered by type 2 synaptic appositions during this 36-week time period. The time course of the type 2 synapses development is compared to that of the spine synapse development described in previous studies (Lund and Holbach, '91; Lund et al., '91), and it is clear that on both neuron groups this inhibitory synapse population is put in place and refined later than the spine synapses. These findings suggest that each cortical neural circuit has a unique time course for its early development within an overall time window (Rakic et al., '86), or sensitive period (Hubel and Wiesel, '70). Visual deprivation, although causing the alpha and beta neurons to adopt a more similar temporal and numerical developmental pattern than normal, did not prevent acquisition and loss phases of type 2 synapses or the assumption of a normal numerical loading by 36 weeks of age. PMID- 1894768 TI - Synaptic organization of starburst amacrine cells in rabbit retina: analysis of serial thin sections by electron microscopy and graphic reconstruction. AB - The synaptic organization of starburst amacrine cells was studied by electron microscopy of individual or overlapping pairs of Golgi-impregnated cells. Both type a and type b cells were analyzed, the former with normally placed somata and dendritic branching in sublamina a, and the latter with somata displaced to the ganglion cell layer and branching in sublamina b. Starburst amacrine cells were thin-sectioned horizontally, tangential to the retinal surface, and electron micrographs of each section in a series were taken en montage. Cell bodies and dendritic trees were reconstructed graphically from sets of photographic montages representing the serial sections. Synaptic inputs from cone bipolar cells and amacrine cells are distributed sparsely and irregularly all along the dendritic tree. Sites of termination include the synaptic boutons of starburst amacrine cells, which lie at the perimeter of the dendritic tree in the "distal dendritic zone." In central retina, bipolar cell input is associated with very small dendritic spines near the cell body in the "proximal dendritic zone." The proximal dendrites of type a and type b cells generally lie in planes or "strata" of the inner plexiform layer (IPL), near the margins of the IPL. The boutons and varicosities of starburst amacrine cells, distributed int he distal dendritic zone, lie in the "starburst substrata," which occupy a narrow middle region in each of the two sublaminae, a and b, in rabbit retina. As a consequence of differences in stratification, proximal and distal dendritic zones are potentially subject to different types of input. Type b starburst amacrines do not receive inputs from rod bipolar terminals, which lie mainly in the inner marginal zone of the IPL (stratum 5), but type a cells receive some input from the lobular presynaptic appendages of rod amacrine cells in sublamina a, at the border of strata 1 and 2. There is good correspondence between boutons or varicosities and synaptic outputs of starburst amacrine cells, but not all boutons gave ultrastructural evidence of presynaptic junctions. The boutons and varicosities may be both pre- and postsynaptic. They are postsynaptic to cone bipolar cell and amacrine cell terminals, and presynaptic primarily to ganglion cell dendrites. In two pairs of type b starburst amacrine cells with overlapping dendritic fields, close apposition of synaptic boutons was observed, raising the possibility of synaptic contact between them. The density of the Golgi impregnation and other technical factors prevented definite resolution of this question. No unimpregnated profiles, obviously amacrine in origin, were found postsynaptic to the impregnated starburst boutons.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1894769 TI - Cytogenesis in the monkey retina. AB - Time of cell origin in the retina of the rhesus monkey (Macaca mulatta) was studied by plotting the number of heavily radiolabeled nuclei in autoradiograms prepared from 2- to 6-month-old animals, each of which was exposed to a pulse of 3H-thymidine (3H-TdR) on a single embryonic (E) or postnatal (P) day. Cell birth in the monkey retina begins just after E27, and approximately 96% of cells are generated by E120. The remaining cells are produced during the last (approximately 45) prenatal days and into the first several weeks after birth. Cell genesis begins near the fovea, and proceeds towards the periphery. Cell division largely ceases in the foveal and perifoveal regions by E56. Despite extensive overlap, a class-specific sequence of cell birth was observed. Ganglion and horizontal cells, which are born first, have largely congruent periods of cell genesis with the peak between E38 and E43, and termination around E70. The first labeled cones were apparent by E33, and their highest density was achieved between E43 and E56, tapering to low values at E70, although some cones are generated in the far periphery as late as E110. Amacrine cells are next in the cell birth sequence and begin genesis at E43, reach a peak production between E56 and E85, and cease by E110. Bipolar cell birth begins at the same time as amacrines, but appears to be separate from them temporally since their production reaches a peak between E56 and E102, and persists beyond the day of birth. Muller cells and rod photoreceptors, which begin to be generated at E45, achieve a peak, and decrease in density at the same time as bipolar cells, but continue genesis at low density on the day of birth. Thus, bipolar, Muller, and rod cells have a similar time of origin. The maximal temporal separation of cell birth is between cones and amacrine cells so that cell generation exhibits two relatively distinct phases: the first phase gives rise to ganglion, horizontal, and cone cells, and the second phase to amacrine, bipolar, rod, and Muller cells. In addition, cells of the first phase are generated faster than the second phase cells, and there are differences in the topography of spread of labeled cells between the two phases. Each cell class displays a central-to-peripheral gradient in genesis, although the spatiotemporal characteristics of the gradients differ between the classes.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1894770 TI - Cutaneous multilobated T-cell lymphoma with aggressive course. AB - Cutaneous multilobated T-cell lymphoma is an uncommon variant of skin-based peripheral T-cell lymphoma typically characterized by cutaneous nodules in elderly patients and a chronic clinical course. We report a case of the disease that led to the patient's death within 2 years after onset. This disease may be associated with a more aggressive clinical course than generally recognized. PMID- 1894771 TI - Malignant schwannoma associated with xeroderma pigmentosum in a patient belonging to complementation group D. AB - A 43-year-old man with xeroderma pigmentosum, XP97TO, was allocated to complementation group D. He had had moderate photosensitivity at age 1 year and freckles by age 6 but no neurologic abnormalities. Nevertheless, his fibroblasts in culture had the XP-D phenotype. They showed a sevenfold hypersensitivity to killing by 254 nm ultraviolet radiation and a diminished level (29%) of unscheduled DNA synthesis. Phototesting revealed delayed maximum erythema at 72 hours after UVB exposure and a lowered minimal erythema dose. Lentigo maligna developed on the patient's face, and a rapidly growing malignant schwannoma was found on the left trigeminal nerve. This may be the first case of a peripheral nervous tissue neoplasm in xeroderma pigmentosum. PMID- 1894772 TI - Porokeratosis arising in a burn scar. AB - A histologically verified porokeratosis arose in a burn scar on the back of a 47 year-old man. This phenomenon has not been previously reported. We discuss the literature on porokeratosis, the relation between epidermal and dermal injury, and the genesis of this lesion. PMID- 1894773 TI - Acanthosis nigricans and a rectal carcinoid. AB - Malignant acanthosis nigricans is often related to adenocarcinomas of the gastrointestinal tract, but it has also been found to coexist with tumors of the amine precursor uptake and decarboxylation system. It can precede, accompany, or follow the appearance of the underlying tumor. Evaluation of our patient's new onset acanthosis nigricans led to the discovery of an asymptomatic rectal carcinoid tumor. To our knowledge, this is the first report of acanthosis nigricans associated with a carcinoid tumor of the rectum. It emphasizes the importance of considering underlying malignancy in the evaluation of patients with acanthosis nigricans. PMID- 1894774 TI - Mycosis fungoides in childhood: an unusual presentation. AB - Mycosis fungoides, a cutaneous T cell lymphoma, is rare in childhood and adolescence. We report a case of mycosis fungoides in a 9-year-old boy initially at a site of benign reactive lymphoid hyperplasia. PMID- 1894775 TI - Periorbital necrobiotic xanthogranuloma and stage I multiple myeloma. Ultrastructure and response to pulsed dexamethasone documented by magnetic resonance imaging. AB - We observed a 40-year-old woman with necrobiotic xanthogranuloma from the inception of indurated eyelid and periorbital infiltrates and concurrent stage I multiple myeloma to resolution of infiltrates in skin and bone marrow after pulsed high-dose oral dexamethasone therapy. Ultrastructural studies revealed lipid vacuoles in epidermal keratinocytes, in dermal histiocytic macrophages, and in vascular and lymphatic endothelial cells. The presence of lipid vacuoles in epidermal keratinocytes has not been reported previously in xanthogranuloma. PMID- 1894776 TI - Proteus syndrome. Ultrastructural study of linear verrucous and depigmented nevi. AB - Proteus syndrome is a rare hamartomatous disorder characterized by multifocal overgrowths that can involve any structure of the body. Clinical manifestations include macrodactyly, hemihypertrophy, subcutaneous masses, exostosis, cerebroid thickening of palms and soles, and linear skin lesions. About 50 cases have been described, but the ultrastructural features of the linear skin lesions have not been characterized. We describe the clinical, histologic, and ultrastructural findings for a 30-year-old patient who had a mild form of Proteus syndrome with linear lesions characterized by a mixed pattern of hyperkeratosis and depigmentation. Light microscopy of the linear nevus showed acanthosis and hyperorthokeratosis. Electron microscopy revealed extensive vacuolation at the interface between melanocytes and keratinocytes, with large aggregations of densely packed granules in the intercellular space. Melanocytes showed only slight degenerative changes. An immunohistochemical study of the expression of epidermal growth factor receptors revealed no significant abnormalities. PMID- 1894778 TI - Erythema multiforme after contact dermatitis in response to an epoxy sealant. AB - A case of erythema multiforme associated with an allergic contact dermatitis in response to an epoxy-based compound is presented. Patch tests revealed a positive reaction to both the epoxy resin and the hardener. Chemicals applied directly to the skin should be considered as a potential cause of erythema multiforme. PMID- 1894777 TI - IgA pemphigus in a child. PMID- 1894779 TI - Focal facial dermal dysplasia: two familial cases. AB - Focal facial dermal dysplasia (or congenital ectodermal dysplasia of the face) is an inherited condition characterized by congenital scarlike lesions on the temples and a wide spectrum of associated facial abnormalities. We report the case of a woman and her son with this disorder. An autosomal dominant inheritance with variable penetrance and expressivity may explain the different clinical expressions of focal facial dermal dysplasia. PMID- 1894780 TI - Annular atrophic lichen planus. AB - We describe a case of generalized, asymptomatic, chronic annular lichen planus. The centers of the large annular lesions were atrophic and had lost their elasticity. Histologic examination revealed an absence of elastic fiber in the center. Electron microscopy revealed fragmented elastic fibers. Examination of early lesions showed that elastolysis had already begun in the heavy cellular infiltration. We conclude that the annular configuration resulted from the elastolytic activity of the inflammatory cells with the formation of foci of localized acquired cutis laxa. PMID- 1894781 TI - Spirochetes in atrophic skin lesions accompanied by minimal host response in a child with Lyme disease. AB - Acrodermatitis chronica atrophicans, which has rarely been observed in the United States, is a late skin manifestation of Lyme borreliosis. A 12-year-old girl who spent summers on Cape Cod presented with a 2-year history of hyperpigmentation and atrophy of the skin on the hands, wrists, and ankles. The skin biopsy specimen of an affected area showed mild dermal fibrosis, a few inflammatory cells, and spirochetes morphologically compatible with Borrelia burgdorferi. An IgG antibody response to B. burgdorferi could be elicited by immunoblotting, but not by enzyme-linked immunosorbent assay. We conclude that this patient had chronic Lyme borreliosis manifested only by indolent infection of the skin. PMID- 1894782 TI - Hydroa vacciniforme with unusually severe scar formation: diagnosis by repetitive UVA phototesting. AB - Hydroa vacciniforme is a rare, chronic, photosensitive disorder manifested in childhood by recurrent vesicles that heal with scarring. Reproduction of vesicles with repetitive UVA phototesting may be an important diagnostic aid. Recurrent eruption resulted in severe scarring of the face and a flexion contracture of the finger in our patient. The clinical features and laboratory evaluation of hydroa vacciniforme are reviewed. PMID- 1894783 TI - Subcutaneous cysticercosis. AB - A case of subcutaneous cysticercosis is presented, and 35 other cases from the literature are reviewed. Patients usually have multiple subcutaneous nodules that are firm, mobile, and sometimes painful, occurring mainly on the trunk and extremities. Diagnosis is made by biopsy; however, radiologic and immunologic studies can be helpful in the diagnosis and work-up. Treatment options include surgery, praziquantel, and albendazole. PMID- 1894784 TI - Cutaneous Histoplasma capsulatum in a nonimmunocompromised patient with previously treated cutaneous Mycobacterium kansasii. AB - This report describes a black woman with a history of cutaneous Mycobacterium kansasii responsive to antituberculous drugs. A culture several years later of cutaneous lesions was also positive for Histoplasma capsulatum. Both cutaneous diseases are rare and most often occur in immunocompromised hosts. There is no known association between these two diseases. This patient may have an as-yet unidentified immunodeficiency that predisposes her to these rare infections. Her case emphasizes the importance of repeat biopsy for atypical skin lesions. PMID- 1894785 TI - PUVA-induced lymphomatoid papulosis in a patient with mycosis fungoides. AB - The occurrence of lymphomatoid papulosis in patients with cutaneous lymphoma, particularly mycosis fungoides, has been described in medical literature. A 68 year-old woman affected by mycosis fungoides in the plaque stage noticed that multiple papulonodular lesions of lymphomatoid papulosis developed suddenly after a few sessions of PUVA therapy. The PUVA induction of lymphomatoid papulosis was confirmed by the appearance of new lesions after a second cycle of PUVA exposure on a limited area of the body. Complete regression of all PUVA-induced lymphomatoid papulosis lesions was achieved within a few weeks with oral prednisone and topical steroids. During the entire treatment the patches and plaques of mycosis fungoides persisted unchanged. PMID- 1894786 TI - Nodular vasculitis (erythema induratum): treatment with auranofin. AB - A patient with nodular vasculitis was treated successfully with oral gold. This therapy is safe and devoid of significant side effects. The rationale and advantages of the use of oral gold in patients with nodular vasculitis are discussed. PMID- 1894787 TI - Unilateral erythromelanosis follicularis faciei et colli in a young girl. AB - Erythromelanosis follicularis faciei et colli is uncommon. Fewer than 20 cases have been reported. Except for one case in a woman and one case of unilateral distribution, all other reported cases have been bilateral in young male patients. We report the first case of unilateral distribution in a white girl. PMID- 1894788 TI - Xanthoma disseminatum: a case with extensive mucous membrane involvement. AB - A 37-year-old man had red or brownish papules on his face, chest, and groin, where they coalesced into plaques. Endoscopic examination revealed the presence of small xanthomatous papules on the mucous membrane of the stomach. A biopsy specimen revealed a dense infiltrate of histiocytes, foam cells, Touton giant cells, and inflammatory cells. The diagnosis of non-X histiocytosis was confirmed by immunohistochemical studies of the infiltrate. PMID- 1894789 TI - Anetodermic prurigo nodularis (with Pautrier's neuroma) responsive to arotinoid acid. AB - A woman had symmetrically distributed pruritic nodules for more than 40 years. Microscopically they were characterized by proliferation of nonmyelinated nerve fibers (Pautrier's neuroma) and a total absence of epidermal involvement. Anetoderma developed at the site of former nodules. Her condition responded favorably to repeated retinoid therapy with regression of nodules in those sites in which retinoid dermatitis had developed. PMID- 1894790 TI - Culture of bovine embryos in deproteinized hemodialysate-supplemented media and immature mouse uterine horns. AB - Bovine morulae (d 6) were used to evaluate embryonic development in a deproteinized hemodialysate, agar embedding, and in the uterus of the immature mouse. Agar-embedded embryos were cultured in Ham's F-10 and 10% steer serum either (treatment 1) immediately after collection or (treatment 2) 24 h after storage in the uterus of the immature mouse. Unembedded embryos were cultured in Ham's F-10 containing (treatment 3) 10% steer serum, (treatment 4) 1% deproteinized hemodialysate CLB1107, or (treatment 5) 1% de-proteinized hemodialysate CLB1107 and 10% steer serum. A greater percentage of the embryos reached the hatched blastocyst stage after culture in treatments 1, 3, 4, and 5 (38.1, 34.6, 28.6, and 21.1%) than in treatment 2 (9.5%) in which embryos were stored in the immature mouse uterus for 24 h prior to in vitro culture. Final development scores for unembedded and agar-embedded embryos cultured in Ham's F 10 (5.5 +/- .3) and 10% steer serum (4.9 +/- .4) were similar and higher than those of embryos cultured in deproteinized hemodialysate CLB1107 (4.2 +/- .4), deproteinized hemodialysate CLB1107 and steer serum (4.2 +/- .4), or immature mouse uteri (3.4 +/- .4). It is concluded that deproteinized hemodialysate supplementation at 1% (vol/vol) failed to enhance embryonic development in vitro. Moreover, bovine morulae were unaffected by agar embedding and were able to develop to a limited extent following short-term storage in the uterus of the immature mouse. PMID- 1894791 TI - Effect of chronobiological alteration of the circadian rhythm of prolactin and somatotropin release in the dairy cow. AB - The objective of this study was to determine if a skeletal photoperiod administered at the appropriate time of a 24-h day could stimulate prolactin and somatotropin release in dairy cattle. Cows in mo 8 of gestation were exposed to either 12 to 13 h of continuous light or to three skeletal photoperiods consisting of a total of 8 h of light. Cows in the skeletal photoperiod light regimens received 6 h of light from 0500 to 1100 h and a 2-h light pulse at either 1500 to 1700 h, 1800 to 2000 h, or 2100 to 2300 h. Cows exposed to the light regimen pulse at 1800 to 2000 h exhibited a circadian rhythm of prolactin and somatotropin release. The mean prolactin and somatotropin concentrations were also higher in this treatment. It is concluded that a circadian rhythm with a photosensitive phase is present for prolactin and somatotropin release in the lactating dairy cow. The photosensitive phase for both hormones occurs between 13 and 15 h after subjective dawn. The expression of the circadian rhythm of these hormones depends on the photoperiod to which cows are exposed. PMID- 1894792 TI - Duodenal rapeseed oil infusion in early and midlactation cows. 4. In vivo and in vitro adipose tissue lipolytic responses. AB - In vitro glycerol and FFA releases from adipose tissue were studied in early (wk 3, trial 1) and midlactation (wk 19 to 26, trial 2) multiparous Holstein Friesian cows receiving a duodenal rapeseed oil infusion (1.0 to 1.1 kg/d). In trial 2, in vitro basal FFA release, basal FFA: glycerol ratio, and isoproterenol-stimulated FFA and glycerol releases were higher in perirenal adipose tissue from oil infused cows. Plasma FFA concentration also was higher in oil-infused cows before and after intravenous isoproterenol injection. In trail 1, basal and stimulated glycerol and FFA releases from perirenal (but not subcutaneous) adipose tissue tended to be lower in oil-infused cows. This was probably linked to a lower milk production potential of oil-infused than of control cows which introduced a bias in energy balance. The basal FFA:glycerol ratio tended to be higher in oil infused cows in both adipose tissues, suggesting a lower rate of reesterification inducted by oil, as was the case in trial 2. The alpha 2-agonist clonidine decreased perirenal adipose tissue glycerol release in cows and treatments in which the responses to 4 x 10(-7) M isoproterenol were higher. In vivo and in vitro lipolytic responses were lower in trial 2 than in trial 1, except the in vitro maximally stimulated lipolytic rate, which probably reflected a long lasting teleophoretic adaptation to ensure energy needs of lactation. This study indicated that oil infusion affected both beta- and alpha 2-adrenergic responses and that postpartum lipid mobilization did not seem to be reduced by the exogenous unsaturated fatty acid supply. PMID- 1894793 TI - Duodenal rapeseed oil infusion in early and midlactation cows. 5. Milk fatty acids and adipose tissue lipogenic activities. AB - Lipogenic activities of perirenal adipose tissue were investigated in early (wk 3) and midlactation (wk 19 to 26) cows that received a duodenal rapeseed oil infusion (1.0 to 1.1 kg/d). In midlactation, oil infusion resulted in a decreased rate of fatty acid synthesis from acetate and a decreased rate of the activities of fatty acid synthetase and glucose-6-phosphate dehydrogenase, whereas lipoprotein lipase activity tended to increase. The rate of glucose incorporation into glyceride-glycerol and the activities of glycerol-3-phosphate dehydrogenase and malic enzyme were not significantly affected. Fatty acid C14:0 content of perirenal adipose tissue was decreased, and fatty acid C18:2 and C18:3 contents were increased in oil-infused cows. In early lactation, rates of acetate incorporation into fatty acids and activities of fatty acid synthetase and lipoprotein lipase were very low. Activities of glucose-6-phosphate dehydrogenase and glycerol-3-phosphate dehydrogenase were lower in the early than in the midlactation trial. Oil infusion did not change the measured parameters. In both trials, percentages and yields of milk fatty acids C18:1, C18:2, and C18:3 were increased, whereas those of C14:0 and C16:0 were decreased by oil. Calculated transfer rates of absorbed fatty acid C18:2 from oil to milk fat were 16 to 26%. Results suggested that oil fatty acids affected adipose and mammary de novo lipogenesis in a direct way without affecting fatty acid esterification in adipose tissue or total fat secretion in mammary tissue. PMID- 1894794 TI - Effect of naturally occurring coagulase-negative staphylococci infections on new infections by mastitis pathogens in the bovine. AB - Microbiological data from 1123 uninfected quarters and 216 quarters with preexisting coagulase-negative staphylococci infections were analyzed to determine the influence of infection status on subsequent new infection rate. Overall, prevalence of new infections in uninfected quarters was approximately two times that in quarters already harboring a coagulase-negative Staphylococcus infection. New infections by coagulase-negative staphylococci were greater in uninfected quarters than in quarters with preexisting coagulase-negative staphylococci infections. However, no differences were observed between uninfected and infected quarters in number of new infections by major pathogens (Staphylococcus aureus, streptococci, and coliforms). No differences were observed in uninfected or coagulase-negative Staphylococcus-infected quarters in infections with minor pathogens compared with major pathogens. The influence of individual coagulase-negative Staphylococcus species on new infections was also analyzed. However, numbers of existing infections by Staphylococcus species other than Staphylococcus chromogenes were limited. Therefore, the protective capacity of each coagulase-negative Staphylococcus species was difficult to assess. Overall, a significant restriction of bacterial invasion was observed in quarters with a preexisting infection. These results suggest that quarters harboring a coagulase-negative Staphylococcus infection suppress colonization of the mammary gland by mastitis-causing pathogens. PMID- 1894795 TI - Serratia species isolated from bovine intramammary infections. AB - Intramammary infections from which Serratia spp. were isolated were studied over a 32-mo period in a research dairy herd consisting of approximately 120 lactating cows. A total of 29 Serratia spp. intramammary infections were detected and accounted for 9% of all Gram-negative bacterial intramammary infections. Serratia marcescens was the most common Serratia spp. isolated. Origin of intramammary infections was 48.3% during the first half of the dry period, 31% during the last half of the dry period, and 20.7% during lactation. A total of 64% of intramammary infections that were first detected during the first half of the dry period persisted to calving. Geometric mean number of lactation days infected for all infections was 55. Intramammary infections that originated during the first half of the dry period were present in lactation for a significantly greater number of days compared with intramammary infections new during the last half of the dry period or lactation. A total of 48% of infections were clinical. Serratia spp. intramammary infections tended to be of long duration compared with other Gram-negative bacterial intramammary infections and were highly associated with the dry period. PMID- 1894796 TI - Role of magnesium in the dietary cation-anion balance equation for ruminants. AB - Eight midlactation Holstein cows (four primiparous) were assigned to replicated 4 x 4 Latin squares with a 2 x 2 factorial arrangement of treatments. The basal diet was formulated to contain 0 milliequivalents (Na + K) - Cl/100 g of diet DM. Treatment diets of high and low dietary cation-anion balance were achieved by adding appropriate amounts of supplemental Na + K (added on an equivalent basis) or Mg to the basal diet. Milk and protein yield were increased as well as DMI and FCM for Na + K diets The high concentration of cation increased milk fat percentage. The cation-anion balance (using Mg as a cation) had no effect on any of the production parameters observed. The higher cation-anion balances increased blood bicarbonate levels and plasma Na. Urinary Ca excretion was increased for the Mg diets. Urinary pH increased with both the source of cation (Na + K) and the concentration of cation (high) in the diet. other minerals were unaffected in milk, plasma, or urine. Responses measured in this trial reflect treatments calculated using the equation milliequivalents (Na + K) - Cl/100 g diet DM or (Na + K) - (Cl + S)/100 g diet DM, suggesting that Mg plays a minor role in dietary cation-anion balance. PMID- 1894797 TI - Water, sodium, potassium, and chlorine metabolism of dairy cows at the onset of lactation in hot weather. AB - Water, Na, K, and Cl balances, blood plasma composition, and urine and fecal outputs were studied in 5 high yielding cows (greater than 30 kg/d milk) at 2 wk prepartum and at 2 and 7 wk postpartum during the summer in Israel. Cows were fed complete diets with electrolyte content exceeding dietary recommendations. Plasma volume, as assessed by hematocrit changes, was greater postpartum, probably due to increased heat load and water turnover. Milk secretion markedly increased electrolyte output, which was compensated for only partially by increased intake. This was associated with marked reduction of electrolyte losses in excreta, particularly that of Na and Cl. On the basis of urea excreted in the urine, it seems that the current practice of abruptly increasing protein content of the diet at the onset of lactation might reduce the efficiency of dietary protein utilization, compared with efficiency of protein utilization at a later stage of lactation. The need to excrete excessive N also adversely affected the water and electrolyte balances. At initiation of lactation, when DMI is still limited and hot weather obstructs its rapid increase, the current recommendations for electrolytes as a percentage of the ration do not meet the needs. PMID- 1894798 TI - Regulation of in vitro palmitate oxidation in liver from dairy cows during early lactation. AB - Regulatory effects of carnitine, glucose, some glucogenic compounds (propionate, pyruvate, alanine, lactate, glycerol, and fructose), ketone bodies (acetate, acetoacetate, and beta-hydroxybutyrate), and insulin on oxidation of palmitate were studied in slices of liver obtained from high producing dairy cows during early lactation. A total of 77 biopsies of liver from 21 multiparous Holstein cows (36 +/- 16 d postpartum) was used. L-Carnitine increased oxidation of palmitate to CO2 by more than twofold and oxidation to acid-soluble products by about fourfold. Propionate decreased oxidation of palmitate in liver slices incubated without added carnitine, but the decrease was lessened by carnitine. Pyruvate, lactate, and alanine increased palmitate oxidation, especially in the presence of carnitine. Glycerol, glucose, and insulin tended to decrease palmitate oxidation in the absence of carnitine. Fructose tended to decrease oxidation to CO2 but did not affect oxidation to acid-soluble products. Acetate and acetoacetate decreased oxidation of palmitate, whereas beta-hydroxybutyrate decreased palmitate oxidation in the absence of carnitine but increased palmitate oxidation in its presence. In general, carnitine decreased the inhibitory effects of compounds that decreased palmitate oxidation but increased the stimulatory effects of compounds that increased palmitate oxidation. PMID- 1894799 TI - Duodenal rapeseed oil infusion in early and midlactation cows. 3. Plasma hormones and mammary apparent uptake of metabolites. AB - Rapeseed oil was infused continuously (1.0 to 1.1 kg/d) into the duodenum of Holstein x Friesian multiparous cows during the first 3 wk of lactation (oil treatment, 6 cows versus 6 controls, early lactation trial) or after 100 d of lactation (midlactation trial, 9 cows in a crossover design). In the midlactation trial, plasma glucose, 3-hydroxybutyrate, and free glycerol were not affected by oil infusion. Postprandial plasma NEFA were higher in oil-infused than in control cows; plasma triglycerides, phospholipids, and cholesterol were significantly increased in oil treatment. Plasma insulin was lower and somatotropin higher in oil-infused cows, whereas insulin-like growth factor-I and triiodothyronine were not affected. During the early lactation trial, there were few significant effects of oil infusion on measured plasma metabolites and hormones. Preprandial glucose and NEFA were lower in oil treatment during wk 2, preprandial phospholipids were higher in wk 1 and 3, and free cholesterol was higher in wk 1. Responses of plasma glucose and NEFA to insulin challenge were not clearly affected by oil treatment during either trial. Differences in plasma triglycerides between jugular and mammary veins were higher in oil treatment in both trials. Oil infusion did not affect jugular-mammary differences of other metabolites except for a slight increase in cholesterol esters in midlactation. The relationships between jugular-mammary differences and jugular plasma concentrations showed that up to 24, 27, 54, and 17% of jugular glucose, NEFA, triglycerides, and 3-hydroxybutyrate apparently were taken up by the mammary gland. PMID- 1894800 TI - Influence of canola fat on yield, fat percentage, fatty acid profile, and nitrogen fractions in Holstein milk. AB - Effects of canola fat on feed intake, yield, and composition of milk of early lactation dairy cows were investigated. Concentrate mixtures containing 0, 2.5, 5.0, 7.3, and 9.6% added fat as Jet-Sploded whole canola seed (0, 4.5, 9.0, 13.2, and 17.4% of DM, respectively) were fed to 15 cows in diets containing 60% concentrate and 40% forage (DM basis). Diets contained 16.5% CP, 30% alfalfa silage, and 10% whole crop oat silage (DM basis). There was a trend for a cubic effect on DMI, a quadratic effect on milk yield, and a small, but significant, linear decrease in milk protein percentage with increasing level of canola seed; the decrease was primarily in the casein fraction. Although milk fat percentage was not altered, addition of Jet-Sploded canola seed caused a substantial reduction in some short- and medium-chain fatty acids and a concomitant increase of as much as 65% in the concentration of C18:1. Results suggest that canola fat from Jet-Sploded whole canola seed can be included up to 5% of dietary DM without negative effects on DMI and with a net positive effect on milk yield. PMID- 1894801 TI - Effects of grain level and protein source on yield, feed intake, and blood traits of lactating cows fed alfalfa silage. AB - Multiparous Holstein cows (n = 27) averaging 590 kg BW were allotted at 3 wk postpartum to nine trios blocked on the basis of similar calving date. Animals were fed alfalfa silage for ad libitum intake and remained in the experiment until wk 11 of lactation. Cows within each trio were assigned randomly to either a medium level of concentrate fed at 1.8% BW containing soybean meal or a low level of concentrate fed at 1.3% BW containing either soybean meal or fish meal. The three treatments were designed to give similar CP intake as percentage of BW from the concentrate. Intake of DM and milk yield were measured daily, and BW and milk composition were recorded weekly. Blood was sampled during wk 7 of lactation. Total DMI was higher for cows fed concentrate at 1.8% BW than for those fed at 1.3% BW. Silage DMI was similar across treatments and averaged 2.17% BW. Milk production, 32.0 kg/d, and milk composition, 3.95% fat, 2.90% protein, and 5.07% lactose, were similar for all treatments. Cows fed at 1.8% BW gained 11.0 kg, whereas those fed at 1.3% BW lost 8.4 and 7.4 kg, respectively, when given soybean meal or fish meal, but these differences were not significant. Prefeeding plasma concentrations of NEFA were higher for cows fed fish meal, which was related to their greater weight lost at wk 7 of lactation compared with those fed soybean meal. Level of concentrate and protein of low or high rumen degradability resulted in similar milk production for cows averaging 32.0 kg/d during early lactation. PMID- 1894802 TI - Hypoxia in neonatal calves: effect on intestinal transport of immunoglobulins. AB - The effect of reduced oxygen tension in arterial blood (hypoxic hypoxia) for 24 h postpartum on the absorption of colostral Ig was studied in 12 neonatal calves. During this period, inspired air for hypoxic calves contained 10.5% O2, whereas that for normoxic calves contained 21% O2. After 24 h, inspired air for all calves contained 21% O2. Three dietary regimens also were imposed during the initial 24-h period: colostrum at 0 and 12 h, whole milk at 0 and 12 h, or fasting. Colostrum was fed to all calves at 24, 36, and 48 h. During the initial 24-h period, means for arterial partial pressure of oxygen were 26 and 73 mm Hg for hypoxic and normoxic calves, respectively. In those fed colostrum at 0 and 12 h, hypoxia extended the period of Ig absorption from 20 to 40.5 h. In calves fed whole milk or those that were fasted, no such effect was noted. These observations suggest that the effect of hypoxia on the cessation of Ig absorption by the small intestine is mediated through a secondary and as yet undetermined mechanism. PMID- 1894803 TI - Hypoxia in neonatal calves: effect on selected metabolic parameters. AB - The effect of reduced oxygen tension in arterial blood (hypoxic hypoxia) for 24 h postpartum on selected metabolic parameters was studied in 12 neonatal calves. During this period, inspired air for hypoxic calves contained 10.5% O2, whereas that for normoxic calves contained 21% O2. After 24 h, inspired air for all calves contained 21% O2. Three dietary treatments also were imposed during the initial 24-h period: colostrum at 0 and 12 h, whole milk at 0 and 12 h, or fasting. All calves were fed colostrum at 24, 36, and 48 h and whole milk at 60 and 72 h. Parameters included plasma glucose, lactate, fructose, and IgG; arterial blood gases; and pH. Arterial partial pressure of oxygen was maintained near 25 mm Hg throughout the period of hypoxia. Arterial partial pressure of carbon dioxide was unchanged during the period of hypoxia (approximately 45 mm Hg) but was lower (39 mm Hg) in posthypoxic calves. Glucose tended to be lower in hypoxic calves; however, this difference was not statistically significant. Hypoxic calves had significantly higher plasma lactate concentrations contributing to a progressive primary metabolic acidosis. PMID- 1894804 TI - Treatment of wastewater from a whey processing plant using activated sludge and anaerobic processes. AB - Wastewater from a whey processing plant was treated in two on-site pilot plants, a three-stage activated sludge plant and an anaerobic reactor, each of which had the capacity of treating 230 L/h of wastewater. The activated sludge treatment was very effective. It reduced 99% of 5-d biochemical oxygen demand of the plant wastewater (from an average of 1062 to 9 mg/L) and 91% of total Kjeldahl nitrogen (from 109 to 10 mg/L) after a total retention time of 19.8 h. The intermediate 5 d biochemical oxygen demand reductions were 86% after 3.8 h in the first stage and 97% after another 8 h in the second stage. The completely mixed anaerobic reactor reduced only 87% of 5-d biochemical oxygen demand after 2 d of retention. However, with an additional 8 h of activated sludge treatment the total 5-d biochemical oxygen demand was reduced by 99%. Both pilot plants were operated smoothly in spite of the considerable fluctuations in pollutant levels of the plant wastewater. PMID- 1894805 TI - Partial purification and characterization of native plasminogen activators from bovine milk. AB - At least four native plasminogen activators were detected in bovine milk, and two partially purified plasminogen activators were characterized. The plasminogen activators were dissociated from casein proteins by treatments with sulfuric acid and dimethylformamide. The plasminogen activators in the resulting fractions were partially purified with size exclusion, affinity, or metal chelate chromatographic techniques. Molecular weights of the two partially purified plasminogen activators were 47.2 and 30.5 kDa by gel electrophoresis. Size exclusion chromatography gave a molecular weight of 43.2 kDa for the first plasminogen activator. The isoelectric points of the two plasminogen activators were in the pH range 6.2 to 6.7. Because activity was not enhanced by the presence of fibrinogen fragments in a plasminogen activator assay mixture and decreased when human anti-urokinase Ig were added, at least some bovine milk native plasminogen activators appear to be urokinase-type plasminogen activators. PMID- 1894806 TI - Properties of proteases from milk somatic cells and blood leukocytes. AB - Proteolytic activity of proteases associated with somatic cells isolated from high SCC milk and proteases associated with leukocytes isolated from bovine blood was assayed at pH 6.6 and 5.2 in a model system consisting of a beta-casein (.96%) substrate in Jenness/Koops buffer. Intact beta-casein and casein proteolysis products were measured by densitometric analysis of SDS-PAGE gels. Relative proteolytic activity was expressed as percentage degradation of beta casein after 24 h at 37 degrees C per 1 x 10(6) cells/ml. Proteolytic activity associated with somatic cells isolated from bovine milk was 27.5 and 13.6% at pH 6.6 and 5.2, respectively. Proteolytic activity associated with leukocytes isolated from bovine blood was 16.0 and 8.4% at pH 6.6 and 5.2, respectively. Proteolytic activity at pH 6.6 was significantly higher for the somatic cells isolated from milk than for leukocytes isolated from blood. The reason for the difference in proteolytic activity of leukocytes isolated from blood of a healthy cow versus somatic cells isolated from milk produced by a cow with mastitis is not known. Further work is needed to determine whether the difference may be caused by a higher proportion of activated macrophages in somatic cells isolated from milk produced by cows with mastitis than in the leukocytes isolated from blood of healthy cows. PMID- 1894807 TI - Effects of daily exogenous oxytocin on lactation milk yield and composition. AB - Eighty-four Holstein cows were used to determine effects of exogenous oxytocin on 305-d milk production and health. Cows were assigned at parturition by parity group to treatments: 1) oxytocin group, animals received an injection of 1 ml (20 IU) of oxytocin at each milking throughout lactation and 2) control group, animals received no injection. Oxytocin injections were given in the thigh region within 3 min following the initiation of udder preparation and immediately prior to machine attachment. Udder preparation consisted of forestripping and manual cleaning (10 to 20 s) and drying (5 to 10 s) of teats. Cows were milked in a parlor, and milk yield was recorded at each milking. Milk samples were collected from each cow biweekly for milk fat, protein, and somatic cell count determination. Individual lactations were modeled using Woods' lactation equation; resulting coefficients were analyzed using ANOVA. The oxytocin group produced 849 kg more milk during the lactation than the control group, with a significant difference occurring after peak milk yield. This suggests that exogenous oxytocin maintained greater persistency during lactation. No significant differences existed for milk fat or protein percentages. The use of exogenous oxytocin at milking increased lactation milk production with no apparent effect on health. PMID- 1894808 TI - Antibiotic residue prevention methods, farm management, and occurrence of antibiotic residues in milk. AB - The objective of this study was to determine associations among the occurrence of antibiotic residues in bulk milk and various farm management practices. Ninety four dairy farms were visited after antibiotic residues were detected in samples of their bulk milk (case farms) along with an equal number of residue-free farms (controls). Farmers completed questionnaires designed to elicit details of management practices used on farms and methods employed for prevention of antibiotic residues. Factors were initially examined unconditionally for statistical association with occurrence of residues; then multivariate associations were determined using multiple logistic regression. After adjusting for herd size in a logistic model, the risk of residues in milk was observed to increase in association with the frequent use of part-time labor in the milking of cows. The risk of residue occurrence was decreased in association with the use of milk residue test kits, when the farmer believed that increasing the dose of antibiotic required an increase in the withholding time of milk, and when tie stall and pipeline milking systems were used rather than milking parlors or tie stall and dumping station systems. PMID- 1894809 TI - Application of portfolio theory in decision tree analysis. AB - A general application of portfolio analysis for herd decision tree analysis is described. In the herd environment, this methodology offers a means of employing population-based decision strategies that can help the producer control economic variation in expected return from a given set of decision options. An economic decision tree model regarding the use of prostaglandin in dairy cows with undetected estrus was used to determine the expected return of the decisions to use prostaglandin and breed on a timed basis, use prostaglandin and then breed on sign of estrus, or breed on signs of estrus. The risk attributes of these decision alternatives were calculated from the decision tree, and portfolio theory was used to find the efficient decision combinations (portfolios with the highest return for a given variance). The resulting combinations of decisions could be used to control return variation. PMID- 1894810 TI - Actions of bovine somatotropin on polymorphonuclear leukocytes and lymphocytes in cattle. AB - Objectives were to determine 1) in vitro effects of bST on function of polymorphonuclear leukocytes and lymphocytes and 2) in vivo effects of bST on leukocyte function of heifers fed to maintain medium or high growth rates. When administered in vitro, bST did not affect function of polymorphonuclear leukocytes. [Methyl-3H]thymidine incorporation by resting lymphocytes was stimulated by 1000 ng/ml bST. When given in vitro, bST did not further enhance [methyl-3H]thymidine uptake by mitogen-stimulated lymphocytes cultured at 38.5 degrees C but reduced the depression of mitogen-stimulated proliferation caused by incubating cells at 42 degrees C. When bST was administered in vivo, phagocytosis and killing of Escherichia coli by polymorphonuclear leukocytes from bST-treated heifers were not different from cells of control heifers. As measured by [methyl-3H]thymidine uptake after stimulation with phytohemagglutinin, lymphocytes from bST-treated heifers responded similarly to those of control heifers when incubated at 38.5 degrees C, but the depression in [methyl 3H]thymidine uptake due to culture at 42 degrees C was less for lymphocytes obtained from bST-treated heifers. In conclusion, bST had little effect on function of polymorphonuclear leukocytes but could promote proliferation of lymphocytes in vitro and protect cells from effects of elevated temperature. PMID- 1894811 TI - Relationships among milk yield, metabolism, and reproductive performance of primiparous Holstein cows treated with somatotropin. AB - Thirty-two primiparous Holsteins were assigned to receive 0, 5.15, 10.3, or 16.5 mg/d recombinant bST. Treatment began between 28 and 35 d postpartum and continued until 60 d prior to next expected calving or 400 d postpartum. Metabolic hormones and metabolites were measured in blood weekly during the first 10 wk of treatment, and progesterone was measured in milk twice weekly to assess ovarian activity until conception. Milk production (305 d, actual) was 8350 +/- 562, 8348 +/- 515, 9571 +/- 515, and 9070 +/- 515 for cows given 0, 5.15, 10.3, or 16.5 mg/d and did not differ statistically. Insulin, glucose, NEFA and blood urea nitrogen were not influenced by dose of bST. However, insulin-like growth factor-I increased linearly with dose of bST. Days from parturition to first detected estrus, days open, and services per conception did not differ among groups; however, days from parturition to first service increased with dose of bST. Rate of detection of estrus decreased with dose of bST, resulting in a longer interval to first insemination. The lower rate of detection of estrus in bST-treated cows may have been associated with reduced expression of estrus. Additional statistical analyses were conducted to determine the relationship between metabolism, milk production, and reproduction over all doses of bST. There was a negative correlation between 305-d milk yield and glucose (r = -.44) and insulin (r = -.46) concentrations during 30 to 100 d postpartum. In stepwise regression analyses, insulin accounted for 21% of the variance in 305-d milk yield. Glucose and NEFA accounted for 18% of the variance in days open, and there was a negative correlation (r = -.32) between glucose and days open. Days open and milk production were not correlated. PMID- 1894812 TI - Effect of bovine somatotropin on production and reproduction in prepubertal Friesian heifers. AB - This experiment was conducted to evaluate the effect of bST on average daily gain, onset of puberty, first lactation milk yield, and reproductive efficiency in Friesian heifers. Heifers (n = 16 per treatment) were allocated to either: 1) control (1.5 ml of vehicle) or 2) bST (15 mg of bST in 1.5 ml of vehicle) using a randomized complete block design. Subcutaneous injections of bST were administered once daily from 7 mo of age for 120 d or until heifers reached puberty. Heifers were weighed every 2 wk, and blood samples were collected twice weekly after heifers reached 200 kg. Progesterone concentrations were used to determine onset of puberty. Heifers were bred between 16 and 18 mo of age and, following parturition, milk yield and composition were recorded twice weekly and once every 2 wk, respectively. Heifers assigned to bST treatment had an average daily gain (kg) of .8 compared with .7 in control heifers. Number of days from birth to onset of puberty for bST-treated heifers was 401 compared with 381 for control heifers. Treatment with bST had no effect on milk yield, milk composition, or reproductive efficiency during the first lactation. These data demonstrate that daily administration of bST to Friesian heifers from 7 to 11 mo of age does not affect average daily gain, onset of puberty, reproductive efficiency, or first lactation milk yield of heifers. PMID- 1894813 TI - Milk yield variation concurrent with conception. AB - Milk yield data from herds at the University of Illinois and the University of Wisconsin-Madison were used to characterize milk yield fluctuations concurrent with conception. Analyses were performed on 118 Illinois and 244 Wisconsin cows; milk yields were recorded for 15 d preceding confirmed conception. Conception was confirmed by calving within 11 d of 281 d postbreeding. Each cow's difference between 7-d rolling means for a.m. and p.m. milking yield was subtracted from a.m. yields as a diurnal adjustment. A pattern matching formula that was applied to adjusted yields [( b - a]/a, where a and b were sequential milkings) produced a mean calculated value for the milking nearest conception that was different from all milkings for 15 d preceding conception in Wisconsin data only. Discriminant analysis failed to differentiate between preceding and conception inclusive sequences of adjusted milk yields. Pattern matching formulas applied to individual cow data failed to isolate more than 2% of conceptions when the threshold value was set to eliminate false positives. Results demonstrated low predictive ability for conception using concurrent milk yield fluctuations despite implications of significant mean differences for values that were enhanced by pattern matching formulas. PMID- 1894814 TI - A case-control study of the association between blood selenium and cystic ovaries in lactating dairy cattle. AB - We carried out a case-control study to investigate the association between the risk of developing cystic ovaries and the concentrations of Se in the blood of dairy cows. Cows were from dairy herds in the vicinity of Ithaca, NY. One hundred and thirty-two cystic ovary cases were identified; a similar number of herdmates who did not have cystic ovaries were selected as controls. Whole blood samples were collected from cystic cows and controls in which Se concentrations were determined. Milk samples also were collected and analyzed for concentrations of progesterone. Multivariate logistic regression analysis was used to identify the role of Se in the risk of developing cystic ovaries while controlling for other possible risk factors. Mean Se in blood concentration for cows with cystic ovaries (141 ng/ml) was similar to that of control cows without cystic ovaries (136 ng/ml). The concentration of progesterone in milk was significantly higher in controls than in cows with cystic ovaries. In the multivariate logistic regression analysis, cows with concentrations of Se in blood greater than 169 ng/ml had twice the risk of developing cystic ovaries compared with cows that had Se levels less than 108 ng/ml. PMID- 1894815 TI - Immunoreactive fraction 1 leaf protein and dry matter content during wilting and ensiling of ryegrass and alfalfa. AB - In four experiments with ryegrass and alfalfa, cut herbage was wilted in the field and silage made in 1- or 200-L silos. Direct-cut (mean DM, 20.3%), low wilt (mean DM, 26.0%), medium wilt (mean DM, 36.2%) and high wilt (mean DM, 47.7%) herbages were used. Fraction 1, the most abundant leaf protein, was measured by crossed immunoelectrophoresis using rabbit anti-Fraction 1 serum. In two ryegrass and one alfalfa experiments in which weather conditions allowed rapid drying to high wilt herbage in 24 h, there was no significant loss of Fraction 1 protein. In the second alfalfa experiment, in which wilting was prolonged to 3 d by adverse weather, there was a 70% loss of Fraction 1. Ensiling proceeded normally in the four experiments, with rapid fall in pH and production of VFA, lactate, and NPN; the extent and rates of production were inversely related to DM content. In alfalfa and ryegrass, pH fell below the isoelectric point of Fraction 1 within 8 d. In each ryegrass experiment, a high proportion (58 to 100%) of Fraction 1 in medium and high wilt silages survived fermentation for 28 and 68 d, with lesser amounts in other silages. With alfalfa, however, almost all Fraction 1 protein was degraded at all DM concentrations during fermentation. Fiber-associated protein increased markedly with increases in DM during wilting, and these differences were present in the mature silage of both ryegrass and alfalfa. Digestibility studies with fistulated sheep showed that appreciable amounts of immunoreactive Fraction 1 protein in ryegrass silages were undegraded in the rumen. PMID- 1894816 TI - Effect of grain level and protein source on ruminal fermentation, degradability, and digestion in milking cows fed silage. AB - Five primiparous Holstein cows (483 kg BW) of low productivity were used in a 4 x 5 incomplete Latin square design to study the effects of feeding two levels of grain containing soybean meal and one level of grain containing fish meal on feed intake, milk production, digestibility, and rumen fermentation. Animals all were fed alfalfa silage for ad libitum intake. Collection of data was between wk 11 and 24 of lactation. The four treatments were an all silage diet (control), silage and medium concentrate fed at 1.8% BW containing soybean meal, and silage and low concentrate fed at 1.3% BW containing either soybean meal or fish meal. Treatments other than control were designed to give similar CP intake from the concentrate, which was based on high moisture corn and cob meal. Milk production and composition were similar among treatments except for fat percentage, which was significantly lower for low grain soybean meal. Intake of DM was higher on medium grain soybean meal compared with the other treatments. Average BW and change in BW (.11 kg/d) were not affected by treatments. Digestibility of DM was higher for cows fed grain (68 to 73%) than for those fed the control diet (60%). Generally, feeding concentrate at 1.3 or 1.8% BW and supplementing with soybean meal or fish meal resulted in pH and concentrations of NH3 N and VFA similar to those observed on the all silage diet. Feeding concentrate at 1.3 or 1.8% BW and supplying fish meal or soybean meal did not change feed utilization enough to increase milk production in low producing cows compared with an all silage diet. PMID- 1894817 TI - Milk yield, parity, and cow potential as variables for computerized concentrate supplementation strategy. AB - A trial was conducted in a dairy of a cooperating kibbutz to investigate the cow's response to individual concentrate supplementation according to daily milk production when a feed mixture containing a 50:50 concentrate:forage offered in the bunk free choice. Concentrate supplementation was provided by computerized self-feeders for cows producing over 30 kg milk/d to a maximum of 10 kg/d concentrate (as fed) according to milk production. The results were compared with those cows fed, for ad libitum intake, a total ration of 73:27 concentrate: forage (high control) and 50:50 (low control). The performance variables of individually supplemented cows (milk yield, 4% FCM yield, and BW) were analyzed according to parity and milk yield potential. The results indicated that milk yield itself could not serve as the only variable for individual concentrate supplementation as applied in this experiment. Cows in different parities and with different milk yield potentials may respond differently to the concentrate supplementation strategy, and parity numbers, milk yield potential, and BW, in addition to daily milk yield, are possible variables to be considered when applying this feeding regimen in order to exploit its economic potential efficiently. PMID- 1894818 TI - Dry matter intake from parturition to midlactation. AB - Six years of data from the Purina Research Center were summarized to quantitate relationships among DMI, DIM, BW, and 4% FCM. Cows were fed individually and housed in a tie-stall barn from parturition to 21 wk postpartum. Best overall equation predicting DMI was kg DMI = .008037 x kg BW + .3134 x kg 4% FCM + .2286 x DIM - .002176 x (DIM)2 + .00000705 x (DIM)3, R2 = .64, CV percentage = 11.1. Data were best fit when separate equations were developed for each week postpartum up to 6 wk and then for periods including 6 to 8, 9 to 13, and 14 to 20 wk. The commonly used equation, kg DMI = .02 x kg BW + .33 x kg 4% FCM, overestimated DMI until wk 10 but underestimated DMI thereafter. The NRC multifactor DMI estimates could be lower or higher than equations developed up to wk 8, depending on values chosen within range of several factors. At wk 8 and beyond, NRC estimates were lower than equations developed, even when highest level within range of several factors was chosen. Calculated energy balances resulted in greater and extended energy deficit for cows in their second or later lactation compared with first lactation. Loss of BW alone was a poor indicator of energy status in early lactation. PMID- 1894819 TI - Comparison of ten Friesian strains in Poland for yield traits from first three parities. AB - Milk yield, fat yield, and fat percentage for the first three parities were compared for crosses of Friesian strains from Canada, Denmark, Israel, The Netherlands, New Zealand, Sweden, the United Kingdom, the US, and West Germany with Polish black-and-white cattle. Mixed model multitrait BLUP solutions for milk yield ranked Holstein strains (US, Canada, and Israel) and New Zealand Friesians higher than European Friesian strains for all three parities. Largest difference for milk yield between highest ranking US strain and lowest ranking Polish strain was 1002 kg for first lactation. Rankings for fat yield were similar to those for milk yield. For all three parities, the New Zealand strain ranked highest for fat percentage and the US strain lowest. Although rankings were consistent across parities for all yield traits, differences between Holstein and Friesian strains decreased as parity increased. Holstein strains maintained their superiority for milk and fat yields for all three parities despite difficult environmental conditions and a feeding regimen worse than in their country of origin. PMID- 1894820 TI - Comparison of genetic evaluations from animal model and modified contemporary comparison. AB - Comparisons were made between characteristics of Modified Contemporary Comparison and animal model evaluations with data available for January 1989 USDA-DHIA genetic evaluations. The animal model system's requirement that cows have a valid first lactation record resulted in a decrease in cows and daughters included. New flexible comparison groups were slightly larger for small herds and much smaller for large herds, which resulted in overall smaller and more uniform-sized comparison groups. Determining the optimal method of defining management groups was not undertaken. Correlations between bull evaluations from the two procedures ranged from .92 to .95 across breeds. Increases in reliability over repeatability were substantial for bulls with limited daughter information and small for widely used bulls. Correlations between evaluations for cows born in 1985 were .92 to .96, whereas those for cows born in 1980 (old enough to have daughters affecting animal model evaluations) were lower (.90 to .93), as expected. Reliabilities for cows were .02 to .05 higher than repeatabilities. Cows with more daughters increased more in evaluation and accuracy between the two procedures and were genetically superior. Bulls and cows with more prior information, cows with higher past evaluations, and Holstein bulls with higher past evaluations tended to have larger increases in PTA. Genetic trend estimates were different for the animal model, which resulted in changes in evaluations of various magnitudes depending on breed, sex, and birth year of animal. PMID- 1894821 TI - Management and production factors influencing immunoglobulin G1 concentration in colostrum from Holstein cows. AB - Immunoglobulin G1 concentration was measured in 919 first milking colostrums from Holstein cows during a 4-yr period on a commercial dairy farm. Sources of variation analyzed for effect on colostral IgG1 concentration were season of calving, lactation number, dry period length, intercalving interval, complete lactation milk and fat production, weight of first milking colostrum, and time from calving to first milking. Weight of first milking colostrum was the variable most highly correlated (negatively) with colostral IgG1 concentration (r = -.29). Weight of first milking colostrum and lactation number of the cow were the most significant discriminators between colostrum of low and high IgG1 concentration. The implications of these results for colostrum feeding management are discussed. PMID- 1894822 TI - Duration of estrous cycles subsequent to two injections of prostaglandin F2 alpha given at a 14-day interval in nonlactating Holstein cows. AB - Data from previous experiments in our laboratory indicated that estrous cycles following synchronization with two injections of prostaglandin F2 alpha often averaged more than 21 d. To investigate whether this could be an effect of prostaglandin F2 alpha, 54 mature heifers and nonlactating Holstein cows were used in a crossover experiment in which estrous cycles either occurred spontaneously or followed two injections of prostaglandin F2 alpha at a 14-d interval (induced estrus). One estrous cycle of each type was recorded for each animal. Blood samples were collected twice weekly for analysis of progesterone. Cattle were observed twice daily for estrus with the aid of tail chalking and an androgenized cow. Estrous cycles following induced estrus were longer than those following spontaneous estrus (24.2 vs. 22.7 d). Ninety-two percent of the cycles following spontaneous estrus were 17 to 25 d in duration compared with 71% of the cycles following induced estrus. If the first prostaglandin F2 alpha was given when progesterone was greater than 1 ng/ml, the estrous cycle following treatment was longer than if the first prostaglandin F2 alpha was given when progesterone was less than 1 ng/ml (26.0 vs. 22.6 d). This experiment demonstrates that two injections of prostaglandin F2 alpha increase the incidence of estrous cycles greater than 25 d. Stage of the estrous cycle at time of the first injection of prostaglandin F2 alpha may contribute to this effect. PMID- 1894823 TI - Economic implications of bovine somatotropin use for the Arizona dairy industry. AB - This study examined the impacts of bST on income of dairy producers in Arizona. The nature of milk production in Arizona, the institutional aspects of the Milk Order, and the supply management program of the United Dairymen of Arizona (the only milk cooperative in Arizona) were considered in the model. Prices declined with increased milk yields from bST. Three dairy enterprise budgets demonstrated that gross revenue minus variable costs initially increased for adopters of bST but declined for nonadopters. If government milk purchase increases cause support price reductions, gross revenues less variable costs would decrease for both adopters and nonadopters but more for nonadopters. Adjustments in size of dairy farms would be required if increased milk production due to bST is large enough to result in decreases in milk price support levels. PMID- 1894824 TI - An experimental evaluation of the effectiveness and efficiency of the leadup activity. AB - The positive effects of a leadup activity on the production of intracoronal operative preparations have been documented in earlier studies. However, an absence of certain controls may have jeopardized the validity of the earlier study, and an adequate test of the innovation's efficiency was not undertaken. The purpose of this investigation was to evaluate the effects of a leadup activity implemented as part of the scheduled laboratory course, when the amount of supervision provided to the experimental subjects during the entire course was reduced significantly, and when subjects were assigned randomly to the two conditions. Calibrated raters, blind to group affiliation of products, graded all preparations. Mean scores for the experimental group (n = 35) were superior to those of the control group (n = 29) for all five preparations, and were statistically significantly (p less than .05) higher on three. Self-evaluations were equivalent to rater evaluations for subjects in the experimental group but not for those in the control group. Self-reports suggest that students receiving leadup training used fewer teeth to practice each of the preparation styles. Anecdotal data indicate that instructors in the experimental group may have found their job no more difficult than it had been in the past. It is concluded that the leadup activity improves performance and increases efficiency as measured by the faculty-student ratio and amount of practice required by students. PMID- 1894825 TI - Quality assessment/assurance activities in U.S. dental schools. AB - Quality of health care services has become a major social issue. Accordingly, activities directed toward the assessment and assurance of quality are receiving increased attention in dentistry and dental education. The purpose of this study was to determine the status of quality assessment/assurance (QA) programs in U.S. dental schools. Responses from 48 U.S. schools identify a range of institutional QA activities currently being conducted in dental education. The evaluation and remedial action elements of the QA process are being addressed in a majority of schools; however, the establishment of criteria delineating those elements of a given QA activity area that should be measured is lacking. PMID- 1894826 TI - Communication and persuasion: factors influencing a patient's behavior. PMID- 1894827 TI - Social cognitive theory and relapse prevention: reframing patient compliance. PMID- 1894828 TI - Loss of alloy in cast restorations fabricated by dental students. PMID- 1894829 TI - Surgical procedures in predoctoral periodontics programs. PMID- 1894830 TI - Issues in the dental care management of patients with bloodborne infectious diseases: an opinion survey of dental school seniors. AB - This study revealed some significant findings concerning the views of dental school seniors. Through a series of questions, we determined the opinions that seniors had about treating patients with bloodborne infections and the way they regarded their professional responsibility to provide care to these patients. We were able to identify that the majority of seniors had knowingly treated patients with one of these diseases, and believed that they had a professional obligation to do so. The study showed that these future professionals were aware of the risks related to disease transmission and they had real concerns about those risks; nevertheless, they were prepared to accept their professional obligation to provide care to these individuals. More than half of the survey population was fearful of treating patients with these diseases, and over half indicated that they would not treat these patients given the choice. This fear was compounded by their presumption that other patients would not want to be treated by a dentist who provides care to HBV/HIV patients, and by the presumption of increased cost of infection control. More than three fourths of these dental seniors agreed that treatment of infected patients would place them at higher risk. Nevertheless, in the face of this perceived danger, 62 percent indicated that they were willing to treat these patients, 79 percent said that they were capable of treating them, and 76 percent acknowledged the responsibility of the profession to treat. Another finding of note involves the treatment of infected patients and the effect that treatment experience had on the seniors' attitudes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1894831 TI - Association membership of full-time faculty in dental schools. AB - Based on the current participation rates in the Association, most full-time faculty who are members of the AADS are White males tenured in the clinical sciences. The American Association of Dental Schools has captured a fair share of the full-time dental school faculty as members, but there is still considerable room for growth. In particular, as the composition of the dental school faculty diversifies, we must be sure that all elements of dental education are represented in the Association. Membership in the ranks of junior faculty is low, and currently the members of ethnic minorities and women are disproportionally represented there. There are 2,381 additional potential members among full-time faculty at U.S. dental schools who represent a large and important force for dental education. The effectiveness of the Association would be enhanced by the inclusion of these full-time faculty along with the thousands of part-time faculty, allied dental educators, and members of postdoctoral dental educational programs. In terms of attendance at the AADS Annual Session, almost all the attenders at the meeting this year were Association members (97 percent). Overall attendance at the Annual Session was quite good with about 60 percent of the full time faculty Association members attending. Attendance rates among the categories we investigated did vary somewhat but not as much as membership by category. In general, dental school faculty who join the Association attend the Annual Session. PMID- 1894832 TI - Recommended clinical guidelines for infection control in dental education institutions. PMID- 1894833 TI - There won't be a revolution without clinicians. PMID- 1894834 TI - From clinical trial to health policy--research on urinary incontinence in the adult, Part II. PMID- 1894835 TI - The limits of curriculum. PMID- 1894836 TI - As the war raged. PMID- 1894837 TI - The language of nursing. PMID- 1894838 TI - Justice, caring, and virtue. PMID- 1894839 TI - Human error--a professional dilemma. PMID- 1894840 TI - Career development: our professional responsibility. AB - Literature indicates that nurses' contributions to the health care profession are misunderstood by the general public. Of equal importance is how nurses perceive themselves. The present study attempted to describe the self-image of nurses working in a hospital setting and to determine whether there are differences in self-image between beginning and expert nurses, between caregivers and noncaregivers, between nurses with different levels of education, and between full-time and part-time nurses. Using the Porter Nursing Image Scale, a sample of 363 nurses perceived themselves positively on the three factors: Interpersonal Power, Interpersonal Relations, and Intrapersonal Ability. Significant differences were found between beginning and expert nurses, between caregivers and noncaregivers, between those with BSN and MSN education, and between full time and part-time nurses. The data suggest the importance of graduate-level education for nurses and the need for career advancement and career counseling. PMID- 1894841 TI - Using the connecting process to meet family caregiver needs. AB - Individuals who engage in caregiving responsibilities for dependent family members in the home setting face challenges that are little understood by others outside the circle of care. Because a large portion of energy is devoted to caregiving tasks, caregivers potentially fail to devote attention to meeting their own needs. The purpose of this study was to develop a beginning substantive theory describing the needs perceived by caregivers and the processes by which these caregivers are able to get their individual needs met. Grounded theory methodology was used to facilitate the identification of these needs and processes. This study concluded that the needs for help, hope, and happiness are the most crucial needs of family caregivers. The basic social process of connecting was identified as fundamental to meeting caregiver needs. Subprocesses of misconnecting and disconnecting were identified as concurrent processes that existed as functions of connecting and that affected the connecting process. The connecting process was seen as an organizing concept that could both give direction to the practice of nursing care for caregiving families and lay the foundation for continued research and theory development. PMID- 1894842 TI - Relationship of role conflict and role ambiguity to selected job dimensions among joint appointees. AB - The purpose of this study was to examine perceptions of role conflict and role ambiguity experienced by nurse faculty in joint academic-clinical appointments and non-joint-appointed faculty (traditional faculty), and to examine the relationships of these two constructs with social support, job satisfaction, and propensity to leave the joint appointment. Scholarly productivity of the two groups was also examined. Five hypotheses were proposed. The sample (N = 113) was drawn from the five Canadian university nursing faculties with the largest proportion of joint academic-clinical appointees. Findings indicate that assuming a joint appointment does not necessarily lead to an increase in role conflict and role ambiguity, and that joint appointees do not differ from traditional faculty in levels of role conflict and role ambiguity, scholarly productivity levels, or job satisfaction. Within the joint-appointee group (N = 33), role conflict was significantly higher than role ambiguity, both role conflict and role ambiguity had an adverse effect on job satisfaction and are determinants of intent to leave the joint appointment. In addition, social support was found to have a buffering effect on role conflict. PMID- 1894843 TI - Life and career pathways of deans in nursing programs. AB - The purpose of this study was to describe deans' perspectives on the life and career relationships and experiences that were significant to them and that influenced them in the assumption of the dean's position. A developmental model guided this inquiry and was used to explain the development of these women's personal and professional identities. The study design was naturalistic. Data was collected by survey, life history interviews, and through document search of curriculum vitae. Field notes were recorded throughout the data collection period. Data were analyzed using Spradley's ethnographic analysis techniques consisting of domains, taxonomies, components, and themes. The study yielded the following themes: (1) a pattern of strong valuing by the participants of education and achievement; (2) a pattern of female relationships that provided the deans with role modeling of important leadership behaviors, support, encouragement, and information for making educational and career choices; (3) a pattern of early leadership behavior that included an enjoyment of, or a desire to be in charge. The conclusions of the study were: (1) the Erikson, Levinson Morgan, and Farber models were useful frameworks in studying these deans' life and career pathways; (2) people and relationships played an important role in the lives and the careers of the women studied; (3) the deans' early socialization experiences and relationships contributed to the development of leadership behaviors and positive ego development; (4) Through early family and educational experiences and relationships, the participants in this study developed strong values related to the importance of achievement and education. PMID- 1894844 TI - American Association of Colleges of Nursing essential values: national study of faculty perceptions, practices, and plans. AB - A representative national sample of bachelor's-degree nurse educators (N = 697) were surveyed about the seven professional values identified by the American Association of Colleges of Nursing (1986) in Essentials of College and University Education for Professional Nursing. Participants agreed that these values were representative of values nurses need to use in practice, and that educational opportunities related to these values should be included in the curriculum. Eighty-six per cent of the sample perceived that they included some or all of these values predominantly through the informal lesson plan. Esthetics was the most frequently mentioned value that was not considered in any form in the nursing curriculum. Nurse educators teaching at religious-affiliated institutions, and those who had educational preparation in values, already included these values in their formal teaching (P less than .04 and P less than .0001, respectively) and they had discussions about including them differently in the future more frequently (P less than .005 and P less than .006) than did other educators. Faculty members teaching at religious-affiliated institutions also established more plans for including these values within the curriculum than those who taught at public institutions (P less than .0004). One conclusion from this study was that values may continue to be treated differently than other nursing education content, ie, predominantly through the informal lesson plan. PMID- 1894845 TI - Developing clinical expertise in the care of addicted patients in acute care settings. AB - Patients with problems related to addiction are frequently encountered in acute care hospitals. Behavioral difficulties and other obstacles to treatment often threaten the smooth application of compassionate plans of care for these patients. The authors describe the use of an addiction nurse expert and a group of clinical resource nurses to advance the level of practice at one institution with regard to addicted patients. The work of Benner on the process of skill acquisition in nursing is used as a framework for the discussion. PMID- 1894846 TI - Macroreentry in the infarcted human heart: the mechanism of ventricular tachycardias with a "focal" activation pattern. AB - Endocardial mapping of electrical activity was carried out in 150 patients to guide antiarrhythmic surgery for drug-resistant ventricular tachycardia in the chronic phase of myocardial infarction. In 20 of these patients, the activation pattern of 27 distinct tachycardias was focal and diastolic potentials were recorded at three or more sites. In 26 tachycardias, the sequence of diastolic potentials progressed from the area of latest activation of one cycle toward the "origin" of the next cycle. In two patients, the heart was stimulated during tachycardia, resulting in entrainment of the tachycardia in both. Late potentials were recorded during entrainment at sites where diastolic potentials occurred during tachycardia. In 11 of the 20 patients, endocardial mapping was performed during sinus rhythm. In four of these, late potentials were observed during sinus rhythm at sites where diastolic potentials were recorded during tachycardia. In two patients without late potentials during sinus rhythm, late potentials were observed during stimulation and induced ectopic beats. The results support the concept that the mechanism of several of these tachycardias is based on reentry in a macrocircuit comprising a tract of surviving tissue traversing the infarct and the remaining healthy tissue. They also indicate that the absence of late potentials during sinus rhythm does not guarantee the absence of arrhythmogenic pathways. PMID- 1894848 TI - Value of electrocardiographic leads MCL1, MCL6 and other selected leads in the diagnosis of wide QRS complex tachycardia. AB - To compare the modified precordial leads MCL1 and MCL6 with the conventional precordial leads V1 and V6 and assess the diagnostic accuracy of selected leads for continuous bedside electrocardiographic (ECG) monitoring, 121 wide QRS complex tachycardias were recorded from 92 patients during cardiac electrophysiologic study. As ascertained from intracardiac recordings, 86 tachycardias were ventricular and 35 were supraventricular with aberrant conduction. Early or late peaking of the predominant QRS deflection in lead MCL6 or V6 proved valuable in diagnosing wide complex tachycardia. An interval of less than or equal to 50 ms from the onset of the QRS complex to the predominant peak (or nadir) indicated supraventricular tachycardia; an interval of greater than or equal to 70 ms indicated ventricular tachycardia. The QRS complexes in leads MCL1 and MCL6 were comparable to those in leads V1 and V6 during sinus rhythm. Significant discrepancies in QRS configuration occurred between the modified and conventional precordial leads during ventricular tachycardia, especially between leads MCL1 and V1; however. these differences did not affect diagnostic accuracy. A single MCL1, V1, MCL6 or V6 lead was equally valuable in the diagnosis of wide complex tachycardia and far superior to a single lead II. A combination of leads (MCL1 + MCL6), (V1 + V6), (V1 + I + aVF) or (V1 + V6 + I + aVF) was superior to a single lead or the routinely monitored lead V1 + II combination. PMID- 1894847 TI - Sympathetic neural responses to induced ventricular tachycardia. AB - Although sympathetic mechanisms play a major role in buffering abrupt arterial pressure reductions, including those that occur during tachyarrhythmias, human sympathetic nervous system responses to ventricular tachycardia have not been measured. Muscle sympathetic nerve activity was recorded directly from the peroneal nerve in 16 patients during diagnostic induction of 19 episodes of sustained monomorphic ventricular tachycardia (average rate 189 beats/min, range 130 to 250). Average systolic and diastolic pressures decreased from 149/78 to 61/49 mm Hg by 10 s and increased toward baseline levels to 88/64 mm Hg by 1 min of ventricular tachycardia. Average sympathetic nerve activity increased by 92% at 10 s in direct proportion to arterial pressure reductions and in inverse proportion to ventricular rate and remained 83% above baseline levels at 1 min. The late recovery of arterial pressure during ventricular tachycardia was related significantly to the magnitude of early sympathetic responses. Sympathetic activity tended to lose its discrete bursting pattern during ventricular tachycardia, and power spectral analysis showed that the large sympathetic peaks at the heart rate frequency present during sinus rhythm are absent during ventricular tachycardia. This study is the first to delineate human sympathetic nervous system responses to ventricular tachycardia. The results suggest that in the patients studied, large early sympathetic surges differed from those that occur during sinus rhythm and contributed to hemodynamic stability during ventricular tachycardia. PMID- 1894849 TI - Detection of changes in atrial endocardial activation with use of an orthogonal catheter. AB - The ability of a catheter with an orthogonal electrode configuration to sense differences in the direction of local atrial endocardial activation was tested in 18 consecutive patients with intact retrograde conduction. In all 18, discrimination of anterograde from retrograde conduction at a single atrial site was examined; in 5 of the 18, multiple sites were examined to determine if the discriminatory ability of the catheter was site dependent. The catheter was specially designed with bipoles in the x, y and z directions. A vector was computed for each electrogram during anterograde and retrograde conduction. Electrogram amplitude along the standard bipole was also compared for anterograde and retrograde conduction. Mean electrogram amplitude for the standard bipole was significantly different for anterograde than for retrograde conduction in 17 of 18 patients (mean +/- SD 4 +/- 1.9 vs. 2.7 +/- 1.3 mV; p less than 0.005), with complete separation of amplitude distributions in 4 patients. The electrogram vector during anterograde conduction was significantly different from that during retrograde conduction in all 18 patients (p less than 0.0001), with complete separation of vector distributions in 14. In some patients with multiple site recordings, the choice of site greatly affected separation based on electrogram amplitude or vector, or both. The orthogonal catheter can be used to sense directional differences in local endocardial activation. The catheter shows promise for discriminating anterograde from retrograde conduction and examining the direction of endocardial activation in the heart during an electrophysiologic examination. PMID- 1894850 TI - Echocardiographic estimation of critical left ventricular size in infants with isolated aortic valve stenosis. AB - With the current trend to performing surgical valvotomy for infantile aortic stenosis without cardiac catheterization, there is a need to develop echocardiographic criteria for adequacy of left ventricular size. The echocardiograms and catheterization data of all 25 infants less than 3 months of age undergoing aortic valvotomy for isolated aortic valve stenosis from September 1980 through July 1990 were reviewed. Significant differences (p less than 0.05) between the survivors and nonsurvivors were noted for age at operation (30 +/- 28 vs. 3 +/- 1.5 days), mitral valve diameter (10.1 +/- 1.7 vs. 7.7 +/- 1.5 mm), left ventricular end-diastolic dimension (18.4 +/- 6.4 vs. 11.4 +/- 3 mm), left atrial dimensions (15.3 +/- 3.8 vs. 10 +/- 2.4 mm), left ventricular cross sectional area on the parasternal long-axis echocardiogram (4 +/- 1.9 vs. 2 +/- 1.9 cm2) and angiographically determined left ventricular end-diastolic volume (43 +/- 23 vs. 11 +/- 5 ml/m2). There was no difference with respect to patient weight, body surface area, aortic root dimension or left ventricular ejection fraction. Left ventricular cross-sectional area less than 2 cm2 as measured on the parasternal long-axis echocardiogram was found in 5 of 7 nonsurvivors and 0 of 12 survivors, making this a risk factor for perioperative death (p less than 0.05). Left ventricular end-diastolic dimension less than 13 mm was found in 5 of 6 nonsurvivors and 2 of 17 survivors, making this another risk factor for early mortality (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1894851 TI - Congenitally corrected transposition and Ebstein's anomaly of the systemic atrioventricular valve: association with aortic arch obstruction. AB - Aortic arch abnormalities are uncommon in patients with congenitally corrected transposition of the great arteries. Over a 20-year period, 10 patients with congenitally corrected transposition and Ebstein's anomaly of the systemic atrioventricular (AV) valve were identified. Five neonates had severe systemic AV valve regurgitation with severe coarctation of the aorta (n = 4) or aortic atresia (n = 1) and presented with heart failure. Four died in the neonatal period and one who had coarctation repair died 7 months postoperatively. The remaining five patients with congenitally corrected transposition and Ebstein's anomaly had mild left AV valve regurgitation; none of these had aortic arch obstruction. In neonates who have coexisting Ebstein's anomaly of the systemic AV valve and congenitally corrected transposition, obstruction to aortic arch flow is common. Severe systemic AV valve regurgitation with a morphologic systemic right ventricle may have contributed to low anterograde flow in the ascending aorta prenatally and thereby to the aortic arch abnormality. PMID- 1894852 TI - Influence of calcium administration on the short-term hemodynamic and anti ischemic effects of nifedipine. AB - This prospective study investigated whether pretreatment with intravenously administered calcium would influence the effect of nifedipine on rest hemodynamics and treadmill performance in patients with ischemic heart disease. Seventeen patients were studied after undergoing a qualifying treadmill exercise test that revealed ST segment depression indicative of ischemic heart disease. Study subjects performed three additional treadmill tests as part of the protocol. One treadmill test was obtained from each patient to provide baseline measurements without a preceding intravenous infusion and in the absence of all antianginal drugs including nifedipine; two additional exercise tests were preceded by an infusion and 10 mg of bite-and-swallow nifedipine. The infusions, administered in a randomized, double-blind, crossover fashion, consisted of either 10 ml of 10% calcium chloride (13.6 mEq) in 50 ml of 5% dextrose in water or 5% dextrose in water alone. Rest systolic blood pressure (134 +/- 4.6 mm Hg) was unchanged after placebo infusion (135 +/- 4.6 mm Hg) but decreased to 124 +/- 4.1 mm Hg (p less than 0.01) 25 min after nifedipine administration. Rest systolic blood pressure increased after calcium infusion (from 139 +/- 4.3 to 148 +/- 4.8 mm Hg, p less than 0.01) and then decreased significantly 25 min after nifedipine administration to 135 +/- 4.2 mm Hg (p less than 0.01). Despite a decrease at the time of peak nifedipine effect after either infusion, systolic blood pressure was significantly lower after administration of nifedipine alone than after administration of calcium and nifedipine (124 +/- 4.1 vs. 135 +/- 4.2 mm Hg, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1894853 TI - Limitations of thrombolytic therapy for acute myocardial infarction complicated by congestive heart failure and cardiogenic shock. AB - As many as one quarter of patients treated with thrombolytic therapy present with congestive heart failure or cardiogenic shock. Although thrombolytic therapy has been shown to limit infarct size, preserve left ventricular ejection fraction and decrease mortality in most subgroups of patients, no apparent benefit has been demonstrated in patients with clinical left ventricular dysfunction. The lack of correlation between ejection fraction and other measurements of left ventricular dysfunction such as exercise time, cardiac output, filling pressures, activation of the neurohumoral system and regional perfusion bed abnormalities may partly explain this paradox. Alternatively, lower perfusion rates, higher reocclusion rates, associated mechanical complications or completed infarction may explain these findings. Preliminary data indicate that emergency coronary angioplasty or bypass graft surgery improves survival in selected patients with cardiogenic shock. Because these findings suggest that restoration of infarct artery patency is especially important in patients with clinical left ventricular dysfunction, additional studies are needed in these patients to investigate the potential benefit that new thrombolytic strategies, inotropic or vasodilator agents or intraaortic balloon counterpulsation might offer by augmenting coronary blood flow and improving reperfusion rates. Currently, acute mechanical revascularization should be considered for patients who present with congestive heart failure associated with hypotension or tachycardia and for patients with cardiogenic shock. PMID- 1894854 TI - Comparison of catheter ablation using radiofrequency versus direct current energy: biophysical, electrophysiologic and pathologic observations. AB - The effects of catheter ablation with radiofrequency versus direct current energy were compared in 18 dogs assigned to two groups (of 9 dogs each). Each dog underwent a single ablation at two sites in the left ventricle at energy levels of 100, 200 or 300 J delivered in unipolar configuration to six dogs each. A transient decrease in left ventricular systolic pressure (from 121.3 +/- 24.5 to 94.2 +/- 18.7 mm Hg, p less than 0.01) and wall motion abnormality were noted in dogs with direct current shock. The left ventricular ejection fraction decreased (from 50 +/- 2% to 34 +/- 3%, p less than 0.001) shortly after direct current ablation but improved 4 weeks later to 43 +/- 3%. There were no significant changes in left ventricular pressure, wall motion or ejection fraction in dogs in the radiofrequency ablation group. Sustained ventricular tachycardia (greater than or equal to 30 s) was seen immediately after direct current shock in all dogs, and one dog died of intractable ventricular fibrillation. A 24-h ambulatory electrocardiographic (ECG) monitor obtained immediately after the procedure showed multiple runs of ventricular tachycardia in all dogs exposed to direct current ablation but in only three dogs that underwent radiofrequency ablation. No differences were found in peak creatine kinase, complete blood count with smear and B-beta 15-42 fibrinopeptide levels. Pathologically, direct current induced lesions were larger (mean length x width x depth 10.9 x 7.5 x 5.2 vs. 4.8 x 4.6 x 4.3 mm) and were poorly circumscribed with inhomogeneous margins of necrosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1894856 TI - Transesophageal echocardiographic demonstration of distinct mechanisms for right to left shunting across a patent foramen ovale in the absence of pulmonary hypertension. AB - The optimal visualization of the atrial septum and fossa ovalis by transesophageal echocardiography was utilized to demonstrate saline contrast transit across the atrial septum and to relate it to the motion of the flap valve (septum primum) of the fossa ovalis. In three cases, three distinct mechanisms of right to left interatrial shunting in the absence of right ventricular systolic hypertension were identified: 1) transient spontaneous reversal of the left to right atrial pressure differential with each cardiac cycle; 2) sustained elevation of right atrial pressure above left atrial pressure induced by respiratory maneuvers; and 3) aberrant flow redirection across the foramen ovale due to a large right atrial mass. Any of these three mechanisms may be operative during paradoxic embolism in the absence of elevation of right ventricular pressures. PMID- 1894855 TI - Chronic hypokalemia and the left ventricular responses to epinephrine and preload. AB - The effects of moderate, chronic (5 days) potassium depletion on cardiac function were assessed in 14 normokalemic and 13 hypokalemic open chest, anesthetized dogs. Cardiac responses to intravenous bolus injection of 2.5 micrograms/kg body weight epinephrine (10 normokalemic and 11 hypokalemic dogs) and to rapidly increased preload (8 dogs in each group) were evaluated. Hypokalemic dogs received a low potassium diet plus chlorthalidone. Plasma potassium levels were lower (p less than 0.001) in the hypokalemic dogs (3.2 +/- 0.1 mEq/liter [mean +/ SEM]) than in the normokalemic dogs (4.1 +/- 0.1). The inotropic response to epinephrine was lower in hypokalemic than in normokalemic dogs, the response of the maximal rate of rise of left ventricular pressure was 20% greater (p less than 0.03) and the response of the peak rate of change of ejection power was 60% greater in the normokalemic dogs. The relaxation response to epinephrine (the maximal rate of fall of left ventricular pressure) was 33% lower (p less than 0.02) in hypokalemic dogs. Responses to rapid volume expansion were impaired by hypokalemia; maximal stroke volume index was 31% lower (p less than 0.01), maximal cardiac index was 26% lower (p less than 0.01) and the peak response to the maximal rate of filling was 51% lower (p less than 0.01). There were no differences in basal cardiac function. Therefore, modest potassium depletion within the clinical range impaired the contractile and relaxation responses to epinephrine and preload and impaired rapid filling. PMID- 1894857 TI - Excimer laser-facilitated balloon angioplasty of a nondilatable lesion. AB - Preliminary clinical experience with excimer laser coronary angioplasty shows that it is a safe and effective means of achieving nonsurgical coronary revascularization in selected patients but specific indications for its use are as yet undefined. In the present report a specific indication is proposed for the use of the excimer laser: to facilitate balloon inflation in a rigid stenosis that fails to dilate despite high balloon inflation pressures. PMID- 1894858 TI - Training programs in the United States in adult cardiology, pediatric cardiology and cardiothoracic surgery. PMID- 1894859 TI - Historical perspective on Holter monitoring. PMID- 1894860 TI - ISIS-3. PMID- 1894861 TI - A placebo-controlled trial of continuous intravenous diltiazem infusion for 24 hour heart rate control during atrial fibrillation and atrial flutter: a multicenter study. AB - The safety and efficacy of a 10- to 15-mg/h continuous infusion of intravenous diltiazem were evaluated in 47 patients with atrial fibrillation or flutter who first responded to 20 mg or 20 mg followed by one or more 25-mg bolus doses of open label intravenous diltiazem. Of the 47 patients, 44 responded to the bolus injection and were randomized under double-blind conditions to receive either a continuous infusion of intravenous diltiazem (10 to 15 mg/h) (23 patients) or placebo (21 patients) for up to 24 h. Seventeen (74%) of the 23 patients receiving diltiazem infusion and none of the 21 with placebo infusion maintained a therapeutic response for 24 h (p less than 0.001). Over 24 h, patients receiving diltiazem infusion lost response significantly more slowly than did those receiving placebo infusion (p less than 0.001). Nonresponders to the double blind infusion were given an additional bolus injection of open label intravenous diltiazem and administered an open label 24-h intravenous diltiazem infusion. The overall proportion of patients maintaining a response to a 24-h infusion of intravenous diltiazem under double-blind or open label conditions combined was 83% (34 of 41). Efficacy of the 24-h infusion of intravenous diltiazem was similar in elderly versus young patients, those who did versus those who did not receive digoxin and those weighing less than 84 versus greater than or equal to 84 kg. However, intravenous diltiazem appeared to be more effective in atrial fibrillation than in atrial flutter. No significant untoward effects were noted.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1894862 TI - Relation between ST segment shifts during ischemia and thrombin activity in patients with unstable angina. AB - This study was designed to determine in patients with unstable angina whether specific electrocardiographic abnormalities associated with ischemia, the presence of coronary lesions consistent with thrombosis on angiography or the presence of recurrent ischemia reflects increases in thrombin activity as manifested by increased plasma concentrations of fibrinopeptide A. The concentration of fibrinopeptide A in plasma was increased to 6.7 +/- 3.1 nM for the group as a whole (n = 29). Increases were greater in the 17 patients who exhibited reversible ST segment shifts (10.2 +/- 5.2 nM) than in the 12 patients exhibiting reversible T wave abnormalities alone (1.6 +/- 0.2 nM) (p less than 0.01). Nine of the 17 patients with reversible ST segment shifts who underwent coronary angiography had lesions with morphologic characteristics consistent with atherosclerotic plaque complicated by thrombosis compared with only 2 of 9 patients with T wave changes only (p less than 0.05). Plasma concentrations of fibrinopeptide A were markedly elevated in 7 of the 11 patients in whom complex lesions were noted on angiographic examination. Thus, the occurrence of reversible ST segment shifts identifies a group of patients with unstable angina in whom ongoing thrombosis is likely and who may be particularly likely to benefit from antithrombotic therapy. PMID- 1894863 TI - Progression of coronary atherosclerosis: is coronary spasm related to progression? AB - A total of 239 patients undergoing serial coronary angiography with a concomitant ergonovine provocation test were studied between July 1974 and June 1987. The progression of coronary artery disease was evaluated in relation to risk factors, especially coronary artery spasm. Patients were classified into three groups: 1) new myocardial infarction group (39 patients); 2) progression without infarction group (90 patients); and 3) nonprogression group (110 patients). To assess how risk factors and coronary spasm are related to the occurrence of new myocardial infarction and progression without infarction, 11 variables in the three groups were examined: age, gender, the time interval between the studies, fasting blood sugar, systolic blood pressure, diastolic blood pressure, smoking, serum cholesterol, triglyceride, uric acid and a positive response to the ergonovine provocation test. Multiple regression analysis selected three independent predictors of progression without infarction: cholesterol (p less than 0.01), systolic blood pressure (p less than 0.05) and a positive response to the ergonovine provocation test (p less than 0.001). Multiple regression analysis also selected three independent predictors of the occurrence of new myocardial infarction: fasting blood sugar (p less than 0.01), systolic blood pressure (p less than 0.05) and a positive response to the ergonovine provocation test (p less than 0.001). A positive response to the ergonovine provocation test was the strongest factor for occurrence of both new myocardial infarction and progression without infarction. To evaluate segmental arterial changes, 3,275 coronary artery segments were analyzed in the 239 patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1894864 TI - Demonstration of myocardial reperfusion injury in humans: results of a pilot study utilizing acute coronary angioplasty with perfluorochemical in anterior myocardial infarction. AB - Reperfusion may limit the amount of potentially salvageable myocardium through the introduction of cellular elements into previously ischemic but viable myocardium (reperfusion injury). It has been demonstrated that intracoronary infusion of a 20% intravascular perfluorochemical emulsion (Fluosol) significantly reduces infarct size and results in improved left ventricular function in the canine model. This pilot study was performed to explore the existence of myocardial reperfusion injury in humans. Utilizing Fluosol as a probe in conjunction with emergency coronary angioplasty, 26 patients presenting within 4 h with a first anterior myocardial infarction were randomized to emergency angioplasty or angioplasty followed by a 30-min intracoronary infusion of Fluosol at 40 ml/min. Global and regional ventricular function were assessed immediately and a mean of 12 days after successful angioplasty with contrast ventriculography. Infarct size was semiquantitated with thallium-201 single photon emission computed tomography (SPECT) images before discharge. Twelve patients (six undergoing angioplasty alone, six treated with angioplasty and Fluosol) had an occluded infarct-related vessel (Thrombolysis in Myocardial Infarction [TIMI] grade 0 to 1) at the time of emergency catheterization and were included in the final analysis. At 12 days after successful angioplasty, the improvement in regional ventricular function was greater in patients receiving adjunctive therapy with intracoronary Fluosol versus those undergoing angioplasty alone utilizing both the radial shortening and centerline method, respectively (23 +/- 3.1% vs. 8 +/- 2.3%, p less than 0.02; and -1.6 +/- 0.4 vs. -2.9 +/- 0.2 SD/chord, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1894865 TI - Decreasing survival benefit from cardiac transplantation for outpatients as the waiting list lengthens. AB - Many patients are accepted for cardiac transplantation during a period of clinical instability associated with a high risk of death, even though most can be discharged home to await transplantation. As the waiting lists lengthen, priority is awarded solely on the basis of the waiting time of outpatients, who now usually undergo transplantation after they have already survived a major period of jeopardy. To determine the impact of the current waiting times and priority system on the previously expected benefit offered by transplantation, 1 year actuarial survival without transplantation was recalculated after each month without transplantation for 214 potential candidates with an ejection fraction of 0.17 +/- 0.05 discharged on tailored medical therapy after evaluation. These data were compared with the 1-year survival data of 88 outpatients who underwent transplantation. Actuarial survival after 1 year was 67% on tailored therapy compared with 88% after transplantation (p = 0.009). Death without transplantation was sudden in 43 of 51 patients, resulting from hemodynamic decompensation in 8. For outpatients already surviving 6 months without transplantation, actuarial survival over the next 12 months was 83% without transplantation. Thus, the expected improvement in survival after transplantation would be only 5% over the subsequent year for patients waiting 6 months, which is the waiting time for many outpatients. Such patients should be reevaluated to determine whether transplantation remains indicated during the next year. PMID- 1894866 TI - Cardiac involvement in patients with primary antiphospholipid syndrome. AB - To evaluate cardiac involvement in primary antiphospholipid syndrome, two dimensional and Doppler echocardiographic studies were performed in 34 consecutive patients with this syndrome. All patients had an increased level of serum anticardiolipin antibodies with no evidence of malignancy or systemic lupus erythematosus. The clinical manifestations of primary antiphospholipid syndrome were arterial thrombosis in 14 patients, venous thrombosis in 6 and recurrent fetal loss in 14. Valvular lesions were observed on two-dimensional echocardiography in 11 patients (32%) (9 women and 2 men), aged 24 to 57 years (mean +/- 1 SD 36 +/- 10). Abnormal echocardiographic findings were observed in 9 (64%) of 14 patients with arterial thrombosis versus 1 (17%) of 6 patients with venous thrombosis and 1 (7%) of 14 patients with recurrent fetal loss. The most common echocardiographic abnormality was mitral leaflet thickening, found in five patients; this was associated with mitral regurgitation in three and with combined mild mitral stenosis and regurgitation in one patient. Localized subvalvular mitral thickening was observed in one patient and calcification of the anulus in another. Aortic valve thickening was observed in two patients, one of whom also had a moderate degree of aortic regurgitation. Vegetation-like lesions on the mitral or aortic valve were found in two patients. It is concluded that valvular lesions are commonly found in primary antiphospholipid syndrome, particularly when the syndrome is manifested by peripheral arterial thrombosis. The location and appearance of valvular lesions in this syndrome are heterogeneous. Most patients have no clinically significant valvular disease. Two dimensional and Doppler echocardiographic studies are often informative in these patients. PMID- 1894867 TI - Sustained ventricular tachycardia associated with sarcoidosis: assessment of the underlying cardiac anatomy and the prospective utility of programmed ventricular stimulation, drug therapy and an implantable antitachycardia device. AB - The presentation, cardiac anatomy and utility of programmed ventricular stimulation in seven patients with sustained ventricular tachycardia associated with sarcoidosis are described. The mean patient age was 38 +/- 8 years. Pulmonary involvement was apparent in three patients and no systemic manifestations of sarcoidosis were present in one patient. All patients had electrocardiographic abnormalities at rest and six had a left ventricular ejection fraction less than 45%. All seven patients had left ventricular wall motion abnormalities and five had mitral valve dysfunction. Sustained ventricular tachycardia was easily induced in all patients. Spontaneous sustained ventricular tachycardia was not prevented with corticosteroid administration. Despite antiarrhythmic drug therapy, two patients had sudden cardiac death and an additional four had recurrence of ventricular tachycardia. Four patients had an automatic cardioverter-defibrillator implanted and received drug therapy; all four received appropriate shocks. This report represents the largest descriptive series of consecutive patients with sustained ventricular tachycardia associated with sarcoidosis. Antiarrhythmic drug therapy of ventricular tachycardia in patients with sarcoidosis, even when guided with programmed ventricular stimulation, is associated with a high rate of arrhythmia recurrence or sudden death, or both. Thus, implantation of an automatic antitachycardia device (cardioverter-defibrillator) should be considered as primary therapy in such patients. Furthermore, sarcoidosis should be excluded, with Kveim skin testing if necessary, in any patient with sustained ventricular tachycardia of unknown origin. PMID- 1894868 TI - Patterns in visual interpretation of coronary arteriograms as detected by quantitative coronary arteriography. AB - In part 1 of a three-part study, 14 novice readers and 6 experienced cardiologists interpreted phantom images of known stenosis severity. No difference between the interpretations of experienced and novice readers was detectable. Visual estimates of "moderately" severe stenosis were 30% higher than actual percent diameter stenosis. In part 2 of the study, visual interpretation of percent diameter stenosis from 212 stenoses on 241 arteriograms was compared with quantitative coronary arteriographic assessment. The visual analysis overestimated disease severity in arteries with greater than or equal to 50% diameter stenosis (except for right coronary lesions) and underestimated severity in all arteries with less than 50% diameter stenosis. Of the 241 arteriograms, 40 had quantitative and visual analysis of all three coronary arteries for assessment of significant disease. In only 62% of the cases did visual and quantitative methods agree on the presence of severe disease; visual estimates diagnosed significantly (p less than 0.05) more three-vessel disease. In part 3 of the study, comparison of percent diameter stenosis by visual estimate with quantitative coronary arteriographic assessment before and after balloon angioplasty of 38 stenoses showed that visual interpretation significantly (p less than 0.001) overestimated initial lesion severity and underestimated stenosis severity after angioplasty. PMID- 1894869 TI - Intravascular ultrasound imaging of angiographically normal coronary arteries: an in vivo comparison with quantitative angiography. AB - Intravascular ultrasound, a new technique for real-time two-dimensional visualization of arteries and veins, delineates vessel wall morphology and measures luminal dimensions. This imaging method has been validated with in vitro systems and in peripheral vessels, but there are few in vivo coronary artery studies. Twenty cardiac transplant recipients with no angiographic coronary artery disease were scanned with a 30-MHz intravascular ultrasound catheter from the left main coronary ostium to the mid-left anterior descending coronary artery. Simultaneous angiographic measurements were performed at 76 sites. Ultrasound end-diastolic diameters in two perpendicular axes were 3.8 +/- 0.9 and 3.9 +/- 0.6 mm, respectively, and mean diameter derived from an area determined by planimetry was 3.9 +/- 0.9 mm. Angiographic coronary artery diameters measured with a computer-assisted edge detection system perpendicular to the long axis of the vessel and to the long axis of the catheter were 3.4 +/- 0.8 and 3.6 +/- 0.8 mm, respectively. Luminal diameters measured with the two imaging systems correlated closely, with an r value of 0.86 when ultrasound was compared with the angiographic diameter measured perpendicular to the vessel and 0.88 when compared with the angiographic diameter measured perpendicular to the imaging catheter. Eighty-three percent of the ultrasound-measured diameters were above the line of identity when compared with the simultaneous angiographic measurement. The more the imaging catheter deviated from the long axis of the vessel, the greater was the discrepancy between the ultrasound and angiographic measurements.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1894870 TI - First-pass nuclear magnetic resonance imaging studies using gadolinium-DTPA in patients with coronary artery disease. AB - Nuclear magnetic resonance (NMR) imaging has been shown to accurately portray cardiac anatomy and function. To investigate the potential of NMR imaging for the assessment of coronary stenosis in patients with chest pain, ultrafast NMR imaging in conjunction with a T1 (longitudinal relaxation time) contrast agent was performed in 17 patients with chest pain who had undergone cardiac catheterization. These included 12 patients with significant coronary artery stenoses and 4 who underwent repeat NMR study after myocardial revascularization. Cardiac images at rest were obtained during rapid intravenous injection of gadolinium-DTPA (0.04 mM/kg). Electrocardiographic-gated images were acquired over 380 ms, with repetitive images obtained every 3 to 4 s. After contrast injection, there was pronounced signal enhancement in the right ventricular cavity, followed by enhancement in the left ventricular cavity and myocardium. Regional myocardium perfused by a diseased vessel demonstrated a lower peak signal intensity (p = 0.001) and lower rate of signal increase (p = 0.001) than did myocardium perfused by coronary arteries without stenosis. Repeat NMR study after revascularization showed an increase in peak signal intensity (p less than 0.002). These results demonstrate the clinical potential of dynamic gadolinium DTPA-enhanced NMR imaging for the assessment of coronary artery disease in patients with chest pain. In combination with anatomic and functional NMR imaging, this technique has the potential to provide a comprehensive noninvasive cardiac evaluation of patients with suspected coronary artery disease. PMID- 1894872 TI - What does positron emission tomography teach us about coronary angioplasty? PMID- 1894871 TI - Metabolic and functional recovery of ischemic human myocardium after coronary angioplasty. AB - Although revascularization of hypoperfused but metabolically active human myocardium improves segmental function, the temporal relations among restoration of blood flow, normalization of tissue metabolism and recovery of segmental function have not been determined. To examine the effects of coronary angioplasty on 13 asynergic vascular territories in 12 patients, positron emission tomography and two-dimensional echocardiography were performed before and within 72 h of revascularization. Ten patients underwent late echocardiography (67 +/- 19 days) and eight underwent a late positron emission tomographic study (68 +/- 19 days). The extent and severity of abnormalities of wall motion, perfusion and glucose metabolism were expressed as wall motion scores, perfusion defect scores and perfusion-metabolism mismatch scores. Angioplasty significantly increased mean stenosis cross-sectional area (from 0.95 +/- 0.9 to 2.7 +/- 1.4 mm2) and mean cross-sectional luminal diameter (from 0.9 +/- 0.6 to 1.9 +/- 0.5 mm) (both p less than 0.001). Perfusion defect scores in dependent vascular territories improved early after angioplasty (from 116 +/- 166 to 31 +/- 51, p less than 0.002) with no further improvement on the late follow-up study. The mean perfusion-metabolism mismatch score decreased from 159 +/- 175 to 65 +/- 117 early after angioplasty (p less than 0.01) and to 26 +/- 29 at late follow-up (p less than 0.001 vs. before angioplasty; p = NS vs. early after angioplasty). However, absolute rates of glucose utilization remained elevated early after revascularization, normalizing only at late follow-up.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1894873 TI - The double-balloon and Inoue techniques in percutaneous mitral valvuloplasty: comparative results in a series of 232 cases. AB - Immediate hemodynamic results of percutaneous mitral valvuloplasty were compared in two consecutive series of unselected patients from the same institution undergoing valvuloplasty with the double-balloon (161 patients) or the Inoue balloon (71 patients) technique. Before valvuloplasty, the patient series were comparable with regard to average age, gender repartition and most clinical, electrocardiographic, X-ray and hemodynamic variables. Poor anatomic forms of mitral stenosis were equally distributed in both series (41% vs. 45%, p = NS). The magnitude of mitral valve area increase and of mean mitral gradient decrease during percutaneous mitral valvuloplasty did not differ significantly in the Inoue balloon and double-balloon series (mean +/- SEM 1.1 +/- 0.2 to 1.95 +/- 0.5 and 1.0 +/- 0.2 to 1.97 +/- 0.5 cm2, respectively, for mitral valve area and 12 +/- 3 to 5 +/- 2 and 13 +/- 4 to 5 +/- 2 mm Hg, respectively, for mean mitral gradient). Four cases of 3+ mitral regurgitation occurred in the Inoue balloon series and 7 in the double-balloon series (p = NS). A good immediate result- defined as mitral valve area greater than or equal to 1.5 cm2 with greater than or equal to 25% in mitral valve area gain and mitral regurgitation less than 2+ at the end of the procedure--was observed in 78% of patients in both series. Three cases of tamponade due to chamber perforation and 14 cases of transient air embolism in the right coronary system due to balloon rupture were observed in the double-balloon series.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1894875 TI - Pregnancy weight gain in adolescents and young adults. AB - We examined whether adolescents required greater prenatal weight gains than nonadolescents to deliver equal weight babies following a low-risk pregnancy. Maternal characteristics and monthly weight gains were collected from medical records obtained from a private health maintenance organization (n = 423). Maternal weight gain, gestational age, parity, and cigarette use during pregnancy were significant predictors of infant birth weight in our regression models. Subjects were nonsmokers with a gestational age greater than 37 weeks and a parity equal to 0 who entered prenatal care during the first trimester of pregnancy. Mean total weight gains for the adolescents (16.2 +/- 4.8 kg; n = 51) and adults (15.2 +/- 5.4 kg; n = 65), and infant birth weights were similar. Mean infant birth weight was 3473 +/- 394 g for the adolescents and 3339 +/- 453 g for the young adults, whereas the optimal weight range for newborns is about 3500 3999 g. Modifiable risks are the important predictors of infant birth weight, and adolescents do not appear to require a greater weight gain than young adults to deliver similar weight babies. PMID- 1894874 TI - Amplitude information from Doppler color flow mapping systems: a preliminary study of the power mode. AB - The flow of a saline-glycerin solution with sand particles through a continuous in vitro flow system was imaged by using two commercially available Doppler color flow mapping systems in a power mode (Toshiba SSH-160A and Advanced Technology Laboratories [ATL] Ultramark 9). The images generated from seven solutions with particle concentrations ranging from 0.0001 x 10(12) to 6 x 10(12) particles/liter and a mean velocity of 30 cm/s measured with use of pulsed Doppler ultrasound were used to examine the dependence of the power mode on particle concentration. To examine the velocity dependence, 20 mean velocities ranging from 0.1 to 0.53 m/s (3 to 30 liters/min) and three particle concentrations (1, 3 and 6 x 10(12) particles/liter) in the solution were used. The recorded images were digitized and analyzed off-line. The SUM values, or the adjusted color intensity levels in delineated areas of interest in the displayed flow, were compared. In general, the power mode was sensitive in displaying slower velocity flows; in the selected particle concentration and velocity ranges, it was both velocity and concentration dependent. The specific dependence differed for the two color flow mapping systems. PMID- 1894876 TI - Energy requirements of breast-fed infants. AB - Current recommendations for energy intake are reviewed in light of emerging data on energy intakes of breast-fed infants and on total daily energy expenditure of infants. For determination of energy requirements, the historical approach based on observed intakes of healthy infants is compared with a newly proposed approach based on energy expenditure and deposition. A data set of exclusively breast-fed infants is used to illustrate the circuity of either approach. Energy intake, expenditure, and stores must be evaluated in an assessment of dietary adequacy. Ultimately, energy requirements of infants should reflect growth rate, body composition, and level of physical activity conducive to optimal health and neurobehavioral development. PMID- 1894877 TI - A case-control study of hypocalcemia in high-risk neonates: racial, but no seasonal differences. AB - A role for vitamin D in the defense against falling serum calcium (Ca) concentrations following cord clamping has been suggested. Since race and season are known to affect vitamin D status, we theorized that black race and birth in winter are additional risk factors for neonatal hypocalcemia (NHC). We retrospectively studied 13,462 infants born at University Hospital (Cincinnati, OH) between January 1, 1984 and December 31, 1987. Serum Ca was measured at 24 hours of age routinely in infants with low birth weight (less than 2500 g), preterm delivery (less than 2500 g), preterm delivery (less than 37 weeks), neonatal asphyxia, and diabetic mothers. After exclusion of infants of diabetic mothers (to remove maternal diabetes as a major confounder) and infants with major congenital anomalies, 714 infants remained. In multiple regression analysis, low serum Ca values were significantly associated with low gestational age (p less than 0.01), low Apgar score (p less than 0.01), and white race (p less than 0.01) (R2 = 0.457). Season or month of birth was not significant. In pair-matched analysis controlling for factors other than season, season of birth did not affect serum Ca. In pair-matched analysis controlling for factors other than race, white race was once again a risk factor for hypocalcemia. Thus, low gestational age, low Apgar score, and white race, but not black race and delivery in winter, are risk factors for NHC. We speculate that in our climate and with the prevailing diet in pregnancy, vitamin D deficiency does not appear to play a role in NHC.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1894878 TI - Brief communication: magnesium absorption in human ileum. AB - A novel technique utilizing samples of human distal ileum removed at surgery was used to study magnesium (Mg) absorption. Specimens of isolated absorptive mucosa were obtained by careful dissection of the tissue to remove the muscle layers, and were mounted in flux chambers. Mean tissue Mg concentration in human isolated intestinal mucosa was found to be within the postulated normal range for human tissue. Mucosal to serosal Mg transport was unaffected by ouabain or 2,4 dinitrophenol and sodium fluoride. Overall, the data indicate Mg absorption in distal ileum to be passive in nature, although a minor active transcellular component cannot be excluded. PMID- 1894879 TI - Effect of mitogenic and hormonal stimulation on zinc transport in mixed lymphocyte cultures. AB - Human mixed lymphocyte cultures (hMLC) were used to examine the relationship between mitogenic stimuli (MITO), synthetic human calcitonin (hCT), and human insulin (hINS) on zinc (Zn) transport kinetics. Lymphocytes were isolated using a Ficoll density gradient. The hMLCs were labeled by incubation with 65Zn in either control or MITO-containing media. 65Zn release to equilibrium was then measured in unstimulated and mitogen-stimulated cells treated with hCT and hINS. hCT and hINS were added only during this final incubation due to the rapid response to peptide hormones. Bidirectional transmembrane flux coefficients were calculated using a closed two-compartment model. The hMLCs subjected to MITO stimulation demonstrated a 25% decrease in the fractional efflux coefficient (Kcm) and a 69% increase in the fractional influx coefficient (Kmc) compared with controls. Acute exposure to hINS resulted in a marked increase in Kmc with no significant change in Kcm. Acute exposure to hCT had effects qualitatively similar to those of MITO alone. Neither hormone significantly altered the transport of 65Zn when compared with stimulation with MITO alone. PMID- 1894880 TI - Effects of canola oil on serum lipids in humans. AB - Previous work in this laboratory had shown in a pilot study that canola oil could lower blood pressure and serum cholesterol levels. Attempting to extend this work to a larger cohort over a longer period, a 4-month study using a 30 ml/day addendum of canola oil as the replacement of the edible oils in the usual diet was undertaken in 36 hypercholesterolemic and/or hypertriglyceridemic subjects. Serum low-density-lipoprotein cholesterol (LDL-C) decreased from 173 +/- 9.0 to 160 +/- 10.0 mg/dl, p less than 0.025. Blood pressure, total cholesterol, and high-density-lipoprotein cholesterol (HDL-C) did not change significantly even though the HDL subfractions did, HDL2 decreasing and HDL3 increasing. PMID- 1894881 TI - Studies of consistency of dietary intake during the first four years of life in a prospective analysis: Bogalusa Heart Study. AB - The consistency of intake levels for several dietary components over a 5-year period (age 6 months to 4 years) in a biracial infant-early childhood cohort has been demonstrated. Young children with high intakes of selected dietary components associated with risk of cardiovascular disease (e.g., total fat, saturated fat, dietary cholesterol) continue to have higher intakes as they mature than do their peers. Spearman rank correlation coefficients at a significant level are noted between ages 2 and 4 for the following nutrients: total protein (r = 0.65), animal protein (r = 0.46), total sugar (r = 0.39), sucrose (r = 0.37), starch (r = 0.33), total fat (r = 0.53), saturated fatty acid (SFA, r = 0.48), polyunsaturated fatty acid (PUFA, r = 0.43), and cholesterol (r = 0.49). At 2 years of age, some 47-65% of those in the upper tertile for total fat, SFA, and cholesterol intake remain in the upper tertile at age 4. Persistence of eating behaviors appears to begin as early as age 2, in part because of parental control over food patterns. These observations have implications for reduction of early cardiovascular risk factors in children and adoption of a more prudent dietary intake through consumer education. PMID- 1894882 TI - Effect of diet on bone matrix constituents. AB - Bone formation occurs in an integrated, highly ordered manner, beginning in the embryonic period. Nutrients may affect bone formation by delaying cellular differentiation, altering responses to bone growth factors, affecting supply of needed nutrients, and/or affecting rates of synthesis of the matrix constituents. Several growth factors, both systemic and local, are being identified which affect bone formation. Matrix constituents include collagen and noncollagenous proteins, each of which are thought to have specific roles in bone formation, maintenance, or resorption. Among the nutrients which are known to affect bone formation at a cellular level are vitamins A, D, and K, ascorbic acid, zinc, magnesium, and calcium. Nutrients that are known to affect protein synthesis in general also affect bone formation. It is necessary for nutritionists to consider cellular as well as systemic effects of nutrients on bone formation. PMID- 1894883 TI - Chronic disease risk factors in vitamin/mineral supplement users and nonusers in a farm population. AB - Dietary, anthropometric, and chronic disease risk factors (CDRF) in vitamin/mineral supplement users (U) and non-users (NU) were measured in a farm population consisting of 162 subjects (46% females and 54% males; 20-79 years of age, mean age: 52 years). Subjects were white, except for two black males. Supplements were used by 62 subjects (38%); 47% of females and 31% of males used supplements; 43% of subjects over 50 years of age and 32% of subjects age 50 or under used supplements. Both dietary intake and energy expenditure were measured using 4-day records. Indices of adiposity included body weight, BMI, and estimated body fat. Total cholesterol (TC), high-density-lipoprotein cholesterol (HDL-C), serum ferritin, hemoglobin, hematocrit, zinc, copper, and vitamin C were based on 12-hr fasting blood samples. Dietary intake (excluding supplements) for vitamin/mineral U was greater than NU for vitamin C (p = 0.006), thiamin (p = 0.01), riboflavin (p = 0.03), niacin (p = 0.02), folic acid (p = 0.001), vitamin B6 (p = 0.01), and magnesium (p = 0.019). Vitamin C levels were significantly higher and the sum of four skinfolds was significantly lower among U than NU. In this population, 24% of males and 18% of females had TC levels over 240 mg%; 8% of both males and females had blood pressures (BP) greater than 140/90 mm Hg, while 49% of males and 46% of females had BP between 120/80 and 140/90; and 71% of males were more than 25% fat, and 56% of females were more than 35% fat. Despite the high prevalence of CDRF, there were no significant differences between supplement U and NU. PMID- 1894884 TI - Acceptable daily intake vs actual intake: the aspartame example. AB - This article discusses the acceptable daily intake (ADI) and the postmarketing surveillance of consumption levels for a food additive, using the widely used food additive aspartame (APM, L-aspartyl-L-phenylalanine methyl ester) as an example. The safety implications of the ADI and consumption levels are also discussed. Aspartame has been assigned an ADI of 40 mg/kg/day by the World Health Organization and regulatory authorities in Europe and Canada, and of 50 mg/kg/day by the US Food and Drug Administration. A number of different methods have been used to measure consumption levels of food additives. Consumption estimations for aspartame from one such method, the food intake survey, have been done in the United States, Canada, Germany, and Finland. APM consumption in all age groups and selected subpopulations, even at the 90th percentile, is approximately 2-10 mg/kg/day and is thus well below the ADI. PMID- 1894885 TI - Serum time curve characteristics of a fixed dose of beta-carotene in young and old men. AB - The present study was designed to evaluate age-related differences in serum beta carotene time curve response characteristics when a beta-carotene dose was given in conjunction with 1500 kcal over the course of a day. On two consecutive days, seven old (73 +/- 4 years) and six young (24 +/- 1 years) men were each fed three 500-kcal meals of an isotonic liquid formula diet containing only trace amounts of beta-carotene. On the first day of testing, no supplemental beta-carotene was given (baseline day). A 15 mg dose of beta-carotene was fed with the morning meal on the second day (test dose day). Fasting blood and hourly blood samples were obtained for 8 consecutive hours on both days. Additional blood was drawn 24 and 48 hours after the test beta-carotene dose. There were no statistical differences in baseline beta-carotene concentrations between the two age groups tested, but, because of high individual variability, serum time curve characteristics were adjusted for fasting beta-carotene levels. After adjustment, the postdose serum beta-carotene response was two to three times greater (p less than or equal to 0.04) in young subjects, as evaluated by peak concentration, area under the curve, or ascending slope of the serum response curve. Examination of factors besides age group that may have accounted for these results suggests that the serum response of the elderly may be more a function of body composition and/or serum lipid patterns than of age per se. However, in the present US population, it may not be valid to control for these factors, which are both closely related to aging. PMID- 1894886 TI - Protein intake and urinary excretion of protein-derived metabolites in aging female vegetarians and nonvegetarians. AB - Relationships among age, protein intake, and urinary excretion of protein-derived metabolites were studied in 125 vegetarian and nonvegetarian women ages 40-92. There were 63 women in the vegetarian (AV) group and 62 women in the nonvegetarian (NV) group. Average daily intakes of energy and total animal and vegetable protein were calculated from 7-day dietary records. Twenty-four-hour urine samples were analyzed for total nitrogen, urea, creatinine, hydroxyproline, and inorganic sulfate. Energy intakes for the two groups were similar. AVs consumed less total and animal protein and more vegetable protein than NVs, even though both groups consumed more than the RDA for protein. No significant differences existed between the groups in the urinary excretion of total nitrogen, urea nitrogen, hydroxyproline, or inorganic sulfate. Energy and protein intakes and total nitrogen excretion were lower in older AVs than in younger AVs, while those of NVs increased between 40 and 55 years of age, and decreased among the older NV women. The relationship between these variables and age in NVs was more accurately described by polynomial rather than linear regression models. PMID- 1894887 TI - Studies of women eating diets with different fatty acid composition. I. Plasma lipoproteins and steroid excretion. AB - Moderate changes in dietary fat composition have been recommended to improve plasma cholesterol status. Such changes have not been studied extensively in women. This research evaluates plasma lipoprotein and steroid excretion changes in young women who consumed a diet similar to US average consumption in 1974 [40 en% fat, polyunsaturated (P) to saturated fatty acid (S) ratio, P/S = 0.3, US74] or a diet modified to contain 30 en% fat, P/S = 1.0 (MOD). Following a preexperimental period of self-selected diets, young women were fed the diets for 28-day periods in a crossover design with 10 women at the University of Nebraska, Lincoln, and 10 at Iowa State University, Ames. Plasma lipoproteins and steroid excretion were quantitated and the compositions determined. Data were analyzed for race (five Chinese, 14 Caucasians) and for diet carryover effects, as well as for primary diet effects. In the Chinese women, the US74 diet raised total and very-low-density lipoprotein (VLDL) cholesterol compared to prior self-selected or modified diets; in the Caucasian women the MOD diet lowered total, low-density lipoprotein (LDL), and VLDL cholesterol. The diet carryover was evident in total high-density lipoprotein (HDL) and HDL3 cholesterol. Total HDL and HDL3 cholesterol in response to the US74 diet were unchanged from the MOD diet when the US74 diet followed the MOD diet, but were lower than modified when the US74 diet followed self-selected diets. The US74 diet resulted in greater neutral sterol excretion than the MOD diet; this response was more marked in the self selected, US74, MOD sequence than in the self-selected, MOD, US74 sequence.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1894888 TI - Studies of women eating diets with different fatty acid composition. II. Urinary eicosanoids and sodium, and blood pressure. AB - Dietary fatty acid composition is known to affect various aspects of eicosanoid metabolism. This research was conducted to evaluate effects of a diet similar to the US average consumption in 1974 (40 en% fat, polyunsaturated to saturated fatty acid ratio, P/S = 0.3) or a diet modified to contain 30 en% fat, P/S = 1.0, on eicosanoid metabolism in young women. Following a period on self-selected diets, women in Nebraska and Iowa were fed the diets for 28-day periods in a crossover design. Urinary eicosanoids, sodium (Na) excretion, and blood pressure were determined. Diet effects were confounded by carryover effects. For urinary eicosanoids the sequence of higher saturated fat (SFA) followed by lower SFA resulted in significantly greater excretion, whereas the reverse order of diets did not cause significant changes. Diastolic blood pressure was not affected by diet, but systolic pressure was lower with the modified diet in the lower to higher-SFA sequence. The change from self-selected to experimental diets does not seem to account for the carryover effects. The interpretation is that linoleate is depleted from tissues more slowly than it is repleted. Effects upon Na excretion were related to SFA more than to linoleate in the diet. PMID- 1894889 TI - Studies of women eating diets with different fatty acid composition. III. Fatty acids and prostaglandin synthesis by platelets and cultured human endothelial cells. AB - The aim of this study was to determine how plasma fatty acids (FA) of subjects eating either a diet designed to match the US diet consumed in 1974 in fat content and composition in accord with the HANES I survey (US74) or a diet modified to meet the US Dietary Goal Recommendations (MOD) are altered, and how the changes affect platelet thromboxane (TXB2) synthesis, and prostacyclin (PGI2) and prostaglandin E2 (PGE2) synthesis by cultured human endothelial cells. Following a period of recorded self-selected diets, 10 women ate the US74 diet for 4 weeks, changing to the MOD diet for the next 4 weeks (sequence 1), and 10 ate the MOD diet followed by the US74 diet (sequence 2). Plasma triglycerides, free FA, platelet FA composition, and red blood cell phospholipids responded to the change from self-selected to controlled diets, but differences in responses were not seen between US74 and MOD diets. Red blood cell total FA did not respond to dietary changes. Under collagen but not thrombin stimulation, platelet TXB2 synthesis was correlated with platelet arachidonate concentration but not serum cholesterol. Endothelial cells were isolated from umbilical cord veins and incubated for 72 hours with a 20% medium of the women's plasma. In sequence 1 (high saturated FA to high polyunsaturated fatty acids), but not in 2 (reverse order), plasma from subjects eating the MOD diet decreased (p less than 0.05) basal and thrombin-stimulated PGI2 and PGE2 synthesis by the cells. These cells had a higher content of linoleic acid than cells from subjects eating the US74 diet. Thus, our study suggests that an increase in the intake of linoleic acid from 4.8 to 7.6 en% decreases PGI2 and PGE2 synthesis by human endothelial cells, and supplementation of the diet with linoleic acid has a longer period of effectiveness than its decrease in the diet. PMID- 1894890 TI - Polyunsaturated fats enhance peripheral glucose utilization in rats. AB - Carbohydrate intolerance is positively correlated with saturated fat consumption. In contrast, individuals consuming diets comprised of polyunsaturated fatty acids (PUFA) have a lower incidence of diabetes mellitus (DM). To test the hypothesis that dietary fats may influence insulin sensitivity, insulin-stimulated glucose utilization was estimated in vivo in rats consuming diets enriched with saturated fatty acids (SFA) (cocoa butter), monounsaturated fatty acid (MUFA) (olive oil), or PUFA derived from corn or fish sources. Each test meal provided (as percentage of calories) 45% carbohydrate, 39% fat, and 16% protein. The meals were consumed over an 8-week period. Metabolic clearance rate (MCR) for glucose was significantly higher (p less than 0.01; 5.69 +/- 0.46 and 5.18 +/- 0.29 ml/kg/min) for diets containing fish and corn oil sources, respectively, when compared to olive oil (4.34 +/- 0.32 ml/kg/min) and cocoa butter (4.61 +/- 0.11 ml/kg/min). Although the MCR between the fish and corn oil diets were not significantly different, the steady state plasma insulin concentration was lower during the fish oil meal (75 +/- 20 microU/ml) when compared to the corn meal (112 +/- 13 microU/ml). Fasting plasma insulin concentrations were significantly lower (p less than 0.01) following the PUFA diets compared to the other two diets. Fasting plasma glucose levels, despite being lower in the fish meal, were insignificantly different among the four test meals. Lastly, body weights were comparable among the four groups tested. These results suggest that diets enriched with PUFA enhance peripheral glucose utilization significantly more than diets comprised of MUFA or SFA sources.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1894891 TI - Dietary fat and plasma lipid physical properties in swine. AB - Changes in the lipid composition of swine lipoprotein were induced by feeding highly saturated or highly unsaturated diets. The diet higher in oleic acid, even when this was a highly unsaturated diet, resulted in a lower order parameter (more fluid) than in the other diets, as has been observed by others. This difference could be detected in whole unfractionated lipoprotein and in isolated high-density lipoprotein. Changes in order parameter with changes in cholesterol/triglyceride, reported by others, were not observed, possibly because of the weighted average effect of measuring whole plasma lipoprotein. PMID- 1894892 TI - Inhibition of gastric acid secretion reduces zinc absorption in man. AB - Numerous factors seem to affect zinc absorption. Gastric acid secretion has been demonstrated to facilitate iron absorption. The zinc tolerance test (ZTT with ZnSO4 220 mg p.o.) was performed in 11 healthy volunteers to study the effects of administering the acid secretion inhibitor cimetidine (1 g/day p.o. for 3 days) and to evaluate the influence of HCl gastric secretion on zinc absorption in physiological conditions. Zinc absorption was reduced after cimetidine administration (p less than 0.005), suggesting that gastric pH influences zinc absorption. To rule out any direct effect of the drug on zinc absorption in five other healthy adults we further evaluated zinc absorption by using a different H2 antagonist (ranitidine 300 mg/day for 3 days and 300 mg before the test). Cimetidine was also tested in these subjects at half the dosage administered to the first group of subjects. Gastric acidity was monitored at 60-min intervals throughout the test via a nasogastric tube. The areas under the plasma concentration curves for zinc were significantly reduced after ranitidine (p less than 0.01), but not after cimetidine administration. Gastric acid was also reduced after ranitidine, but not after cimetidine (500 mg) administration, suggesting that gastric acid secretion plays a role in the regulation of zinc absorption in man. PMID- 1894894 TI - Nutrition services for homeless persons. PMID- 1894895 TI - Alternative lipids and metabolism. PMID- 1894893 TI - Hereditary and environmental influences on blood pressure values of premenopausal women and their college-age daughters. AB - Blood pressure (BP) and environmental (dietary/lifestyle) variables were measured in 62 healthy normotensive pairs of premenopausal mothers (44.3 years) and their college-age consanguineous daughters (18.7 years) to estimate the relative contributions of genetic vs environmental factors on BP. As expected, the mothers had significantly higher systolic (SBP) and diastolic (DBP) blood pressures than the daughters (p less than 0.004 and 0.012, respectively). Among the dietary/lifestyle variables measured, mothers were found to have significantly higher mean weight and body mass index (BMI) (p less than 0.009 and 0.001, respectively), and significantly lower lean body mass (LBM) and calcium intake than their daughters (p less than 0.003 and 0.037, respectively). Significant correlations were found between mean BP of the mothers and their mean weight and BMI. No significant correlations existed for the daughters. The familial resemblances between BP of the mothers and daughters were relatively low, i.e., 0.14 for SBP and 0.19 for DBP. From these findings we conclude that the higher BP values with increased age among this healthy female population primarily result from an increase in BMI and a shift from lean to fat mass, as measured by midarm circumference. Our results suggest that environmental factors, i.e., excessive energy intake over time, accompanied by decreased physical activity, are primarily responsible for the greater indices of body fat and the higher BPs observed in this sample of healthy premenopausal women. PMID- 1894896 TI - Are low Cronbach alpha values reliable? PMID- 1894897 TI - Pearson correlation coefficients vs reliability coefficients. PMID- 1894898 TI - Nutrient data for Mexican-American foods: are current data adequate? PMID- 1894899 TI - Breast-feeding policies and routines among Arizona hospitals and nursery staff: results and implications of a descriptive study. AB - In 1988, Arizona's 61 hospitals providing obstetrical services were canvased with regard to hospital routines that favor either breast-feeding or bottle-feeding. Forty-five hospitals provided responses that were used in the survey. Practices favoring breast-feeding, which were reported by a majority of the hospitals (more than 50%), were demand feeding, staff assessment for "latch-on" (the action of nipple presentation and sucking initiation) and positioning, "rooming-in" (the practice of minimal mother-infant separation), and information about follow-up support services. Hospital practices suggested to promote bottle-feeding were the provision of pacifiers and supplemental water or glucose, issuance of formula packs at discharge, and a first feed of sterile water. A positive significant relationship was identified for policies advocating breast-feeding and the prevalence of breast-feeding encouragement from professional staff. Of 44 respondents, 41 indicated that their hospital's policies endorse breast-feeding as the ideal method of feeding healthy newborns. Hospital staff perceived that they encourage mothers to breast-feed and offer support to those who initiate breast-feeding. On the basis of this information, we conclude that dietetics practitioners should evaluate current breast-feeding practices and integrate policies supportive of breast-feeding into the health care system. PMID- 1894900 TI - Perceptions of clinical dietetic practice: continuing education and standards. AB - A survey to examine dietitians' perceptions of the effects of continuing education on dietetic practice and use of standards to measure quality practice was conducted. Continuing education approved for maintenance of professional registration by the Commission on Dietetic Registration (CDR) and continuing education not applicable for registration status (non-CDR) were studied. A self administered questionnaire was mailed to a random sample of 484 registered dietitians from the northeast United States who had been employed in health care institutions for 3 years or more. A response rate of 40% was obtained. The investigation showed a significantly greater perceived improvement in practice from non-CDR continuing education over a 3-year period than from CDR-approved continuing education. Respondents obtaining less than 30 hours of non-CDR and CDR continuing education over a 3-year period derived a significantly smaller perceived improvement in practice than did respondents obtaining more than 30 hours. Personal standards were used to the greatest extent (87%), followed by standards of the Joint Commission on Accreditation of Healthcare Organization (68%), to measure quality practice. This study indicates that practitioners focusing on improving their practice will want to consider the contributions of informal work-related activities as well as CDR-approved continuing education. PMID- 1894901 TI - Perceived continuing education needs of RDs and DTRs. AB - The American Dietetic Association (ADA) Council on Practice Continuing Education Committee conducted a study to ascertain the perceived continuing education needs of registered dietitians (RDs) and dietetic technicians registered (DTRs) to assist ADA and other program providers in developing relevant programming. It surveyed 5,000 RDs and DTRs to determine current and preferred continuing education activities, factors influencing the selection of activities, topics most likely to be selected, and demographic characteristics. Results show that RDs and DTRs use a variety of mechanisms and pursue a large number of topics. Continuing education needs are most often met through locally available activities. Preferred mechanisms are workshops and lectures. ADA and state/district associations are major, but not exclusive, providers of programming. Practitioners tend to choose topics related to their practice area. Topics requested at an advanced level of presentation related to traditional dietetic practice; topics requested at a basic level were new or not specific to nutrition. The data will be incorporated into the ADA continuing education programming plan and will provide direction for ADA's exploration of new methods of continuing education delivery. PMID- 1894902 TI - Measuring short-term dietary intake: development and testing of a 1-week food frequency questionnaire. AB - Measures typically used to assess short-term intake are 24-hour recalls or records of food intake. However, these methods require a large time commitment from both researchers and subjects. Our study sought to develop a more time efficient method of assessing short-term intake by developing a 7-day food frequency questionnaire (7DFFQ). We modified Willett's 1-year food frequency questionnaire to assess intake for a 7-day period. Content validity has previously been exhibited in Willett's work. We assessed criterion validity by comparing the 7DFFQ with 24-hour recalls. Twenty-one female and 20 male college students were asked to recall their previous day's intake three times during a 1 week period. After the last recall, subjects completed a 7DFFQ covering the same week. Data were analyzed by comparing each recall and the mean of the three recalls with values obtained on the 7DFFQ. Analyses revealed high correlations between the mean of the three recalls and the 7DFFQ. Further analysis ranked subjects into quartiles for each nutrient on both measures. Most subjects changed either no quartiles or only one quartile for total energy and each nutrient. Test/retest reliability was assessed by administering the 7DFFQ to a group of women for two consecutive weeks and by administering the 7DFFQ to a group twice 3 hours apart. Pearson's r and intraclass correlations for the two administrations show moderately high reliability over the 1-week period and considerable improvement with the 3-hour administration. The 7DFFQ appears to meet several of the criteria for a measure of dietary intake. PMID- 1894903 TI - Plan IV and V dietetics program recruitment strategies and their perceived success. AB - A recruitment effort is essential to the vitality of the dietetics profession. To gather information about recruitment strategies and to identify recruitment techniques perceived to be successful, we surveyed 258 program directors of approved Plan IV and V programs listed in the 1989 Directory of Dietetic Programs. One hundred thirty-nine questionnaires were completed, a response rate of 55%. On-campus students were recruited primarily from general education or basic nutrition classes or by means of written information placed in campus offices. High school, community college, and junior high school students were usually contacted through career information days, although high school students were contacted more frequently than were community college or junior high school students. Almost half of the respondents made a special effort to recruit underrepresented groups. A variety of strategies had a significant positive relationship with perceived recruitment success. Some involved personal contact for example, meeting with high school science and home economics teachers, attending career information days at community colleges, and having a full-time faculty member assigned to meet with prospective majors. Other strategies involved the development of printed materials and displays. Department or school names that were directly related to nutrition, dietetics, health, science, or professional management were perceived as having a positive effect on promoting the dietetics program. Recruitment strategies perceived to be successful may be a useful starting point for recruitment efforts. The findings indicate recruiting strategies can be categorized into two groups--those that involve personal contact and those that involve the use and development of the print and graphic media. PMID- 1894904 TI - Selection criteria for approved preprofessional practice programs: are they different from those for dietetic internships? AB - Using a mailed questionnaire, we surveyed the directors of 41 approved preprofessional practice programs (AP4) listed in the Directory of Dietetic Programs 1990 and nine programs approved by The American Dietetic Association's Council on Education in December 1989 to determine the relative importance of admission criteria used to select students for AP4s. We compared the results of this study with those of an earlier survey of dietetic internship directors. The AP4 and dietetic internship directors gave significantly different importance ratings to elective courses in professional sciences and courses in the biological/physical sciences. Unlike dietetic internship directors, AP4 directors rated Graduate Record Examination (GRE) score highest (1.4 +/- 1.7 on a 10-point scale). AP4 directors' rating of grade point average (1.8 +/- 1.3) and professional courses (1.9 +/- 1.2) was similar to the internship directors' rating of these criteria (1.7 +/- 0.9 and 1.7 +/- 1.0, respectively). Results indicate that AP4 and internship directors seek similar qualities in students, but that GRE score is more important to AP4 directors. The AP4 directors' emphasis on GRE score may be explained, in part, by the fact that 76% (38 of 50) of these programs are affiliated with a university program, and of those 38 programs, 29 (88%) require graduate credit as a component of the AP4. These data are important to Plan IV/V faculty advisers because students may have misconceptions about differences in AP4 and internship selection criteria. PMID- 1894905 TI - Fat and cholesterol avoidance among Mexican-American and Anglo preschool children and parents. AB - Is a fat-avoidance scale a useful tool for monitoring and tracking dietary fat selections of adults and children? Using a seven-point scale, we addressed this question with 341 preschool children and 421 of their parents participating in a longitudinal study of childhood behaviors in San Diego County, California. Milk type and cooking fat reported in the fat-avoidance scale was compared with data reported in a 24-hour food intake record. An overall 86% agreement for milk type and a 78% agreement for cooking fat were noted. Anglo preschoolers (n = 143) had significantly greater mean scores for fat and cholesterol avoidance than did Mexican-American preschoolers (n = 198). Anglo, but not Mexican-American, women avoided fat and cholesterol more often than did their male counterparts. A significantly higher sum score was noted for Anglo men and women and Mexican American men as education increased. These findings indicate that the fat avoidance scale has a relative validity compared with a 1-day food record, that fat avoidance can be measured, that differences can be noted in a biethnic sample of children and adults, and that the scale has potential for monitoring success in achieving a lower fat and cholesterol intake. PMID- 1894906 TI - Development and testing of a carbohydrate monitoring tool for athletes. AB - Improving carbohydrate intake in athletes will increase muscle glycogen storage. This in turn can improve exercise time and performance by delaying fatigue. However, planning and consuming a diet that contains 60% to 70% carbohydrate is difficult for most athletes. To develop a simple carbohydrate monitoring tool for athletes, we analyzed three sets of 3-day diet records from 17 male endurance runners over a 10-week competitive period and 9 female endurance runners over a 9 week training period. We then developed a simple carbohydrate monitoring tool. To validate the instrument, we compared each athlete's carbohydrate intake as estimated using the instrument with the athlete's actual carbohydrate intake from the 3-day diet records. Mean estimated percents of energy from carbohydrate using the carbohydrate monitoring tool were not significantly different from the actual mean carbohydrate intakes. Examination of individual diets showed that the estimated carbohydrate was always within 2% of the actual carbohydrate. Therefore, the instrument did a good job of estimating the percent of energy from carbohydrate in the diets of endurance runners. This instrument will provide a quick method by which the athlete can assess and improve carbohydrate intake on a daily basis without the use of daily diet records. PMID- 1894907 TI - Providing access to blacks and Hispanics in dietetics education. AB - To increase the number of blacks and Hispanics in dietetics and three other health professions, the Health Sciences Recruitment and Retention Program was developed and implemented in 1985 by the College of Health at Florida International University in Miami. The coordinated undergraduate program assisted in a federal grant to accomplish the objectives of recruiting and retaining minority students. High school and community college students were recruited using a slide/tape presentation featuring black and Hispanic professionals. In addition, the college offered a summer course entitled "Perspectives of the Health Sciences Professions" to students entering their senior year in high school. In this course, students learned how dietitians, medical laboratory scientists, and physical and occupational therapists treat various disease states. Field trips and site visits provided additional exposure to the professions. A summer orientation and tutorial program was established to retain minority students enrolled in the coordinated undergraduate program. We recommend that this program be considered as a model for dietetics educators to use in developing other programs to increase the number of minorities in the profession. PMID- 1894908 TI - Considerations in modifying a semiquantitative food frequency questionnaire. AB - Quantifying dietary intake remains a challenge. Although advances have been made, we are still attempting to find a quick yet reliable intake method. Utilizing brief, frequency-type questionnaires that have already been tested is an attractive option. However, many of us would also like to alter those questionnaires to make them more specific to our study population. The items covered in this article should help to illuminate some of the tissues that must be considered. PMID- 1894909 TI - The Non-Diet Diet: a 100-point scoring system for monitoring weight loss behavior. PMID- 1894910 TI - Relationship of eating attitudes to anthropometric variable and dietary intakes of female collegiate swimmers. PMID- 1894911 TI - Relationships of emotional motivators for eating and body fatness among elderly individuals living in recreational vehicle parks. PMID- 1894912 TI - Long-term supplement users and dosages among adult westerners. PMID- 1894914 TI - Timely statement on labeling of meat and poultry. PMID- 1894913 TI - Timely statement on NCEP report on children and adolescents. PMID- 1894915 TI - ADA policy statement on licensure. PMID- 1894916 TI - Azinphos-methyl residues in apples and spatial distribution of fluorescein in vase-shaped apple trees. AB - Vase-shaped standard apple trees cv. McIntosh were sprayed with azinphos-methyl at pink, pink and 1st cover and 1st cover only. Residue analyses by gas chromatography revealed detectable residues on foliage until mid summer. At harvest, negligible residue levels were found on the peel and the whole apple. On four trees, fluorescein was sprayed in the same manner as the insecticide and maximum levels of the dye were detected on the outside lower canopy along the row. Minimal concentration of fluorescein was detected on the inner upper canopy away from the direction of the row. PMID- 1894917 TI - Microbial degradation of pendimethalin. AB - Microbial degradation of pendimethalin (N-(1-Ethylpropyl)-3, 4-dimethyl-2, 6 dinitroaniline) in vitro was studied. Fusarium oxysporum and Paecilomyces varioti, two soil fungi, in culture media degraded pendimethalin to two metabolites namely N-(1-Ethylpropyl)-3, 4-dimethyl-2-nitrobenzene-1, 6-diamine (II) and 3,4-Dimethyl-2, 6-dinitroaniline (IV). Rhizoctonia bataticola, another soil fungus, decomposed pendimethalin yielding only the latter metabolite (IV). Fungal decomposition of pendimethalin involved nitro reduction and dealkylation. PMID- 1894918 TI - Disappearance of bromopropylate residues in artichokes, strawberries and beans. AB - Residues of Bromopropylate were determine in artichokes, strawberries and beans after foliar spray of acaricide at two rates. The rates used were 1 g/l formulated product (normal recommended) and 1.5 g/l. The residue levels of bromopropylate in the three crops after 14 days were lower than 0.7 ppm and did not exceed the Maximum Residual Level (MRL) recommended by FAO. In the artichokes and strawberries, the total concentration of residues decreased by 50% of the initial level after 2-3 days. Only trace levels of the bromopropylate residues (less than 0.01 ppm) were detected in the "hearts" of the artichokes. Bromopropylate residues in the green beans were also less than 0.8 ppm after the first day of foliar spraying. The kinetic of degradation occurred in two different steps. In the first step (4-6 days) the dissipation of bromopropylate was faster whereas in the second step (7-14 days) the loss of residues was much slower. PMID- 1894919 TI - In vitro effect of dimethoate on the activity of tryptophan pyrrolase in rat liver. AB - Total and holo-enzyme activities of tryptophan 2,3-dioxygenase were measured in vitro in the presence and absence of the organophosphorous insecticide, dimethoate. Addition of dimethoate to the reaction mixture decreased the activities of both total and holo-forms. Total and holo-enzyme activities were decreased by 34% and 26%, respectively, by 1 mM dimethoate. On the other hand, 5 mM dimethoate resulted in 56% and 34% inhibition to total and holo-enzyme activities, respectively. Lineweaver-Burk plot of the total-enzyme activity at different tryptophan concentration in the presence of 2 mM dimethoate gave uncompetitive type of inhibition. PMID- 1894920 TI - Effects of fluorine emission on agricultural products surrounding an aluminum factory. AB - The F concentrations of precipitate dust, agricultural products, and fingernail and hair at the surrounding Al factory were investigated. The F content of dust ranged from 15400 to 42500 micrograms/g dry weight, 190,000 to 380,000 micrograms/g Al. Rice grain contained about 3.4 times more F than that in the control area, but some kinds of agricultural products, egg plants (S. melongena L.), mulberry plants (M. japonica Bailey non Sieb.), and soy beans (G. max (L.) Merrill) were almost equal to that of controls. Also, the high F concentration in the hair and nails of some workers was affected by available F contents in the emission from the factory as well as food and water surrounding the aluminum factory compared with those of control area. PMID- 1894921 TI - Lead and other metals distribution in local cooking salt from the Fofi salt- spring in Akwana, Middle Benue Trough, Nigeria. AB - Energy Dispersive X-ray Fluorescence (EDXRF) technique has been used to determine the concentrations of lead(Pb) and other heavy metals in local cooking salts (LCS) from Akwana village, Middle Benue Trough, Nigeria. The comparison of the distribution of these metals in LCS, 'fake' salt (FS) and the usual common salts (CS) are given. Lead was found to be enriched in LCS by factor exceeding 200 times compared to the other salts. The origin of Pb contamination in the LCS is examined and its effects on the inhabitants of the village are considered. PMID- 1894922 TI - Epidemics and agendas: the politics of nightly news coverage of AIDS. AB - We examine why the exponential growth of AIDS cases or the wide-spread professional perception of a health crisis did not move the epidemic more quickly onto the agenda of public problems. One possible explanation focuses on how the national news media's construction of AIDS shaped the meaning of the epidemic for mass and elite audiences. An examination of nightly news coverage by the three major networks from 1982 to 1989 reveals considerable variability and volatility in their coverage. Topic-driven saturation coverage occurred only during three short periods in 1983, 1985, and 1987, when the epidemic seemed likely to affect the "general population". Only at such moments did public opinion shift and discussion and debate in government begin. Otherwise, the typical AIDS story tended less to sensationalize than to reassure, largely because journalists depended upon government officials and high-ranking doctors to present them with evidence of news. Such sources had interests either in avoiding coverage or in pointing toward breakthroughs; more critical sources, especially within the gay movement, had far less access to the news. In concluding, we considered the prospects and pitfalls of the news media's power to shape the public agenda. PMID- 1894923 TI - Tax administration as health policy: hospitals, the Internal Revenue Service, and the courts. AB - Since 1969 federal tax policy has permitted nonprofit hospitals to turn away indigent patients or to transfer them to public hospitals. The Internal Revenue Service made health policy, but its officials remain convinced that they were not making policy at all. Convinced that it was reasoning from legal principles, the Revenue Service accepted the hospital industry's view of the history and purpose of hospitals. The federal courts further obscured the problem. Moreover, the Revenue Service took no interest in the effects of its ruling on the services provided by tax-exempt hospitals until 1989. We describe these events and seek to explain them by linking the recent history of health policy to the assumptions that govern the making of tax policy. We conclude that the making of health policy by tax officials who are not accountable for it and who believe that they are not making policy at all is not in the public interest. PMID- 1894924 TI - Can the government govern? Lessons from the formation of the Veterans Administration. AB - The federal hospital system for veterans, established in the aftermath of World War I in a context of decentralization, privatization, and rejection of compulsory health insurance, seems an anomaly in health care policy-making. It is actually a good case of how the federal government achieves results in an area fraught with conflict: via normalization of crisis, containment of political decision making, and the association of the program with previously accepted goals (in this instance, workers' compensation). In the veterans' case, political judgments were transformed into scientific and bureaucratic decisions via the pragmatic use of experts. The system worked; the federal government governed. PMID- 1894925 TI - Partnership as a new strategy in mental health policy: the case of Quebec. AB - The notion of partnership is increasingly adopted as a sine qua non for the successful resolution of strategic problems in the field of human services. In this paper, I examine Quebec's recent mental health policy and its operational definition of the concept. I then suggest some of the roots and reasons behind this province's adoption of le partenariat as the basis for policy. I suggest that it is a response to four key strategic problems: (1) the exhaustion of resources and allocation of losses; (2) the loss of faith in government and the consequent need to redefine the role of the state; (3) the loss of faith in professional knowledge and the increasingly forceful voice of alternative and "psychiatric survivor" groups; (4) the problem of overload in pluralist and competitive democracy and, related to this, the ubiquitous search for consensus and frictionless solutions. I conclude that in adopting the language of partnership, policymakers in Quebec and elsewhere are being seduced by the possibilities of neocorporatist ideas applied to the management of human services. PMID- 1894926 TI - Partnerships: a more enthusiastic view. PMID- 1894928 TI - German unification: east meets west in the doctor's office. PMID- 1894927 TI - Selective pregnancy reduction: medical attitudes, legal implications, and a viable alternative. AB - "Selective pregnancy reduction" is a medical procedure used to reduce a multiple pregnancy, often a multiple pregnancy induced by in vitro fertilization or drug therapy. In such instances, healthy embryos are sacrificed in order to maximize the chances of survival of the remaining embryos or to allow the mother to choose the number of babies she wishes to deliver. Physicians appear to rely on Roe v. Wade in assuming the legality of the procedure, although such an assumption may be erroneous. Rather than continue to implant an excessive number of pre-embryos, the American Medical Association and the Association of Obstetrics and Gynecology should adopt guidelines similar to those established by the Voluntary Licensing Authority in London, which limit the number to be inserted to a maximum of three. Careful ultrasound monitoring could ensure that no more than three embryos implant when fertility drugs are used. Such practices would help physicians avoid the many moral, ethical, legal, and philosophical problems caused by selective pregnancy reduction. PMID- 1894929 TI - Indeterminate human immunodeficiency virus type 1 western blots: seroconversion risk, specificity of supplemental tests, and an algorithm for evaluation. AB - The human immunodeficiency virus type 1 (HIV-1) Western blot is indeterminate in 10%-20% of sera reactive by EIA. Eighty-nine individuals with prior repeatedly reactive EIA and indeterminate Western blots were followed prospectively to study the risk of seroconversion and specificity of supplemental tests. Four high-risk cases seroconverted within 10 months after enrollment (seroconversion risk, 4.5%, 95% confidence interval, 1.2%-11.1%). Among cases with p24 bands initially, 4 (18.2%) of 22 high-risk individuals seroconverted compared with 0 of 33 low-risk cases (P = .03). Specificities of HIV-1 culture, serum p24 antigen, polymerase chain reaction, and recombinant ENV 9 EIA were 100%, 100%, 98.6%, and 94.4%, respectively. An expedited evaluation protocol is proposed. Low-risk individuals with nonreactive EIAs upon repeat testing do not need further follow-up; high risk individuals should be followed serologically for at least 6 months, especially those with p24 bands on Western blot. PMID- 1894930 TI - Randomized, double-blind, placebo-controlled, clinic-initiated, Canadian multicenter trial of topical edoxudine 3.0% cream in the treatment of recurrent genital herpes. Canadian Cooperative Study Group. AB - Treatment for recurrent genital herpes using edoxudine 3% cream for 5 days was evaluated in 200 patients in a randomized, multicenter, double-blind, placebo controlled, clinic-initiated trial. Lesion tenderness was predictive of and more sensitive and longer-lasting than the symptom of pain. Among patients receiving placebo, times to crusting (P = .043), cessation of investigator-observed signs (P = .005), lesion-associated signs (P = .02), and groin signs (P = .05) were longer in women. Edoxudine reduced viral shedding in men (mean 2.7 vs. 3.4 days, P = .009) and women (2.0 days vs. 3.5 days, P = .0001). Loss of investigator observed signs (4.4 vs. 6.2 days, P = .002), investigator-observed lesion tenderness (P = .01), lesion signs (P = .02), groin adenopathy (P = .01), and tenderness (P = .01) occurred earlier in women taking edoxudine. Edoxudine was well-tolerated and reduced several signs of herpes in women. Its clinical role in recurrent genital herpes remains to be fully determined. PMID- 1894931 TI - Astrovirus and adenovirus associated with diarrhea in children in day care settings. AB - The relative importance of astrovirus and adenoviruses as etiologic agents of diarrhea among children in day care was examined. Stool specimens from this prospective study were screened for both astrovirus and adenovirus hexon with two new indirect double-antibody assays and for enteric adenoviruses with an EIA specific for serotypes 40 and 41. Astrovirus was detected in a significantly greater percentage of children with diarrhea (4%, 21/524) than of those without (less than 1%, 1/138) (P less than .05); however, no difference between such such children with adenovirus infections was found (8%, 43/565, and 8%, 10/129, respectively). Overall, 30% (13/43) of all adenovirus hexon-positive specimens were enteric serotypes, and by extrapolation, enteric adenoviruses were identified in an equal percentage of children (2%) with and without diarrhea. This study documents the presence of astrovirus and enteric adenoviruses among children in day care in the United States, associates astrovirus with diarrhea in this setting, and suggests that viral agents may be the most common enteric pathogens among children with diarrhea in day care. PMID- 1894932 TI - A pertussis outbreak in a Wisconsin nursing home. AB - The epidemiologic features and clinical spectrum of pertussis in the elderly are poorly understood. In October 1985, the Wisconsin Division of Health investigated an outbreak of pertussis in residents of a nursing home in rural Wisconsin. Clinical information and nasopharyngeal swab and acute- and convalescent-phase serum specimens were obtained from all consenting residents and employees. Of 105 residents, 38 (36.2%) were seropositive, including four who were culture-positive for Bordetella pertussis. Culture-positive residents (age range, 52-81 years) had cough lasting 43-54 days. Three of these residents had paroxysmal cough, and all four had cough that interrupted sleep; none of the residents had cough with apnea or vomiting, and all recovered without sequelae. Of six seropositive residents with clinical pertussis, five lived on the south wing of the facility. Of 104 employees, 8 (7.7%) were seropositive, but none were culture-positive for B. pertussis. The higher attack rate for residents and the clustering of clinical cases were consistent with ongoing transmission within the nursing home. PMID- 1894933 TI - Epidemiology of acute rheumatic fever in a multiethnic, multiracial urban community: the Miami-Dade County experience. AB - During the mid-1980s, several US communities experienced outbreaks of acute rheumatic fever (ARF), often involving predominantly white, middle-class individuals living in suburban or rural settings. The medical records of all patients diagnosed with ARF in Miami-Dade County, Florida, between 1984 and 1988 were reviewed. Thirty-five cases met the revised Jones criteria and were considered definite; four additional cases were classified as probable. Carditis was present in 54%. Of the 39 patients, 32 (82%) were black. The annual incidence of ARF among black children aged 5-14 years was 12.25 per 100,000 compared to 0.71 for other (non-Hispanic white plus Hispanic) children (P less than .001). ARF was centered in the inner city, where the incidence among black children reached 15.21. Despite the multiethnic, multiracial character of Miami-Dade County and the rapid influx of immigrants, ARF in this community remains primarily a disease of underprivileged, black inner-city children. PMID- 1894934 TI - Sexually transmitted diseases in postpubertal female rape victims. AB - Seventy-six postpubertal women were referred from a municipal hospital emergency room within 60 h of sexual assault for evaluation. Of the 76 victims, 20 (26%) had active Chlamydia trachomatis infection detected by culture (11 subjects), a fourfold serologic titer rise (6), or both (3). The risk of acquiring C. trachomatis infection after sexual assault was 3%-16%. Pelvic inflammatory disease was detected in 8 (11%) of the 76 victims. Bacterial vaginosis was diagnosed in 38 women (50%), at least 8 of whom appeared to have been infected during the assault. Trichomoniasis was found in 17 victims (22%), at least 5 of whom may have acquired the infection at the time of the assault. In view of the high rates of these infections and the poor compliance with follow-up (76% [58/76] kept their appointments), all postpubertal victims of sexual assault should be offered treatment with ceftriaxone, 250 mg intramuscularly, followed by 100 mg of oral doxycycline and 500 mg of oral metronidazole twice daily for 7 days. PMID- 1894935 TI - Clinical features and analysis of risk factors for invasive candidal infection after marrow transplantation. AB - Of 1506 marrow transplant patients from 1980 through 1986 reviewed for risk factors for invasive candidal infection defined by positive blood cultures, biopsy, or histologic evidence of tissue invasion, 171 (11.4%) had invasive infection, with a significantly higher incidence in the more recent years of review; 40% (69 patients) had evidence of tissue-invasive disease without fungemia. Of 102 patients with fungemia, 45% had candidemia alone with a mortality of 39%. Mortality in patients with tissue involvement was 90% with or without fungemia. Factors that increased infection were age, acute graft-versus host disease, and donor mismatch. Factors that decreased infection included conditioning with 12 Gy of fractionated irradiation and cyclophosphamide, transplantation for aplastic anemia, and more rapid engraftment. Among fungemic patients, the number of days of fungemia was a risk factor for tissue invasion while more rapid engraftment was protective. PMID- 1894936 TI - A double-blind, placebo-controlled cytogenetic study of oral acyclovir in patients with recurrent genital herpes. AB - The antiherpes drug acyclovir breaks chromosomes in vitro at millimolar concentrations and at highly toxic doses in rodents but does not induce single gene mutations. Recurrent genital herpes patients were examined to determine if such chromosomal damage occurs in peripheral lymphocytes during acute or chronic acyclovir therapy. Patients were randomly assigned to receive acyclovir suppressively and for recurrences, placebo suppressively and acyclovir for recurrences, or placebo suppressively and for recurrences (n greater than or equal to 20 for each group; all treatment double-blind). Normal volunteers and acyclovir-treated cultures served as additional controls. Cytogenetic analyses were done at enrollment (pretreatment), on day 5 of acute acyclovir or placebo treatment for the first postenrollment recurrence (postacute), and at the end of a year on study (postchronic). Cells in metaphase, 150 for each patient, were examined at each time point for structural and numerical chromosomal abnormalities. No cytogenetic effects of chronic or acute oral acyclovir treatment were found relative to lifestyle controls, pretreatment controls, or placebo treatment. PMID- 1894937 TI - Zidovudine improves response to pneumococcal vaccine among persons with AIDS and AIDS-related complex. AB - Antibody responses to 23-valent pneumococcal vaccine were studied in 38 individuals infected with human immunodeficiency virus (HIV), including 6 with asymptomatic infection, 24 with AIDS or AIDS-related complex (ARC) receiving treatment with zidovudine, and 8 untreated AIDS/ARC patients. Antibody responses were significantly higher for asymptomatic persons (aggregate geometric mean, 972 ng of antibody nitrogen (AbN)/ml; P less than .001) and AIDS/ARC patients receiving a median of 12 weeks (range, 4-54) of zidovudine therapy (mean, 369 ng of AbN/ml; P less than .001) when compared with untreated AIDS/ARC patients. Antibody responses among zidovudine-treated AIDS/ARC patients were independent of the dose (mean, 629.2 mg/day; range, 100-1200 mg) or duration of zidovudine therapy. For zidovudine-treated AIDS/ARC patients, persistence of an aggregate antibody response 8 months after vaccination was associated with survival at 14 months after vaccination, whereas waning of response was not. Pneumococcal vaccine should be administered as early as possible in the course of HIV infection. Immunization should be delayed for at least 4 weeks for AIDS/ARC patients initiating zidovudine therapy. PMID- 1894938 TI - A method for the quantification of intracellular zidovudine nucleotides. AB - An assay to quantify the phosphorylation products of zidovudine (AZT) in peripheral blood mononuclear cells (PBMC) was developed. Extracts of PBMC were separated by high-performance liquid chromatography. Eluted AZT mono- (MP), di- (DP), and triphosphate (TP) were collected in separate portions. Treatment with alkaline phosphatase yielded equimolar amounts of AZT, which after solid-phase enrichment were assayed by radioimmunoassay. Detection limit was 0.1 pmol/10(6) PBMC for each nucleotide. Recoveries of 102%-118% were observed. AZT nucleotides were measured in samples from three patients receiving 250 mg of AZT every 12 h. Intracellular concentrations of AZT-MP after 1-2 h ranged from 0.9 to 1.4 pmol/10(6) PBMC and then declined to 0.3-1.1 pmol/10(6) PBMC after 4 h. AZT-DP and AZT-TP reached concentrations of 0.3-0.5 pmol/10(6) PBMC after 1-2 h and could not be detected after 4 h in any of the three patients. Duplicate determinations deviated by less than 20%. PMID- 1894939 TI - Heterogeneity of immunotypes of heat-labile enterotoxins of enterotoxigenic Escherichia coli of human origin. AB - A new technique, checkerboard immunoblotting (CBIB), has been applied to detect and to differentiate heat-labile enterotoxins, (LTs), from enterotoxigenic strains of Escherichia coli of human origin using polyclonal and monoclonal antibodies. Optimal conditions of production and release of LTs were defined using CBIB. LT release was enhanced when E. coli cells were treated with 8 M urea. LT production was highest when E. coli strains were incubated with shaking (200 rpm) at 37 degrees C for 12 h in CAYE-2 medium. Two hundred and five strains of E. coli, isolated from patients with diarrhea in Japan, Thailand, the United States, Mexico, and Brazil, were examined for LT. Of 133 LT-positive strains, 4 (3%) produced an LT that reacted like H-LT-1 (originally isolated from E. coli strain H-74-114) while 126 strains (94.7%) produced LT that reacted like H-LT-2 (originally isolated from strain H-10407) or H-LT-3 (from strain H-240-3). Three strains of human origin (2.3%) produced an LT that reacted like P-LT (produced by E. coli strains of porcine origin). This study shows that CBIB, a simple, efficient, and practical assay, might be useful for epidemiologic surveys and for evaluation of serologic responses to LTs and antitoxic vaccines. PMID- 1894940 TI - Differences in release of tumor necrosis factor from THP-1 cells stimulated by filtrates of antibiotic-killed Escherichia coli. AB - Bacterial products, such as endotoxin, activate mononuclear cells to produce tumor necrosis factor (TNF) and other monokines capable of producing host cell injury. THP-1 cell TNF release in response to bacterial products generated during antibiotic killing of Escherichia coli (ATCC 12014) was evaluated. THP-1 is a mature monocytic leukemia cell line that produces TNF in a dose-dependent fashion in response to purified endotoxin. E. coli were incubated in the presence of amikacin, ciprofloxacin, ceftazidime, cefotaxime, aztreonam, or imipenem at concentrations that killed greater than 99.9% of the organisms. Aliquots of these antibiotic-bacterial cultures were added to THP-1 cells, and TNF concentrations were determined by specific immunoassay. Amikacin and imipenem produced rapid bacterial killing and were associated with low TNF levels. Ceftazidime, aztreonam, and cefotaxime killed E. coli at a slower rate and were associated with significant increases in mononuclear cell TNF responses. Ciprofloxacin produced intermediate TNF levels. Differences exist among bactericidal antibodies in their ability to generate products capable of stimulating mononuclear cell TNF release. PMID- 1894941 TI - Asymptomatic blastomycosis of the central nervous system with progression in patients given ketoconazole therapy: a report of two cases. AB - Ketoconazole (KTZ) has largely replaced amphotericin B as first-line therapy for blastomycosis. However, KTZ penetrates poorly into the central nervous system (CNS), and therapeutic failure may be caused by initially unrecognized CNS infection. Two patients (22% [2/9] of all culture-proven cases of blastomycosis at Grady Memorial Hospital, Atlanta, over 15 years) developed CNS blastomycosis while receiving KTZ. Neither initially had CNS symptoms; both had cutaneous and pulmonary disease that responded to KTZ. If KTZ or other fungistatic imidazoles are to continue as primary therapy for blastomycosis, studies are needed to improve the ability to identify patients likely to experience treatment failure or develop CNS disease. Possibly all patients with disseminated blastomycosis, even those without CNS symptoms, should have lumbar puncture and computed tomography of the head before therapy. Critical evaluation of their immune function also may be required before making a therapeutic decision to use KTZ or amphotericin B. PMID- 1894942 TI - Antifilarial cellular responses detected in a Haitian pediatric population by use of a microblastogenesis assay. AB - Previous reports have demonstrated age-related shifts in antifilarial humoral immune responses in 6- to 10-year-old Haitian children; the responses consisted of elevated parasite-specific IgG2 and IgG3 in amicrofilaremic children and elevated IgG4 in microfilaremic children. In this study, the cell-mediated immune responses to soluble adult and microfilarial extracts of Brugia pahangi, determined by use of a microblastogenesis assay, were examined. Capillary blood samples were collected by finger prick from 176 Haitian children in an area with endemic Wuchereria bancrofti. Antigen-specific cellular responsiveness varied as a function of infection status but not age or sex; amicrofilaremic children had significantly greater responses to adult antigens than did microfilaremic children. Significant responses were detected in children less than 2 years of age; thus, correlations observed between filarial antigen-specific responses and infection status are established early in life. PMID- 1894943 TI - Changes in circulating parasite antigen levels after treatment of bancroftian filariasis with diethylcarbamazine and ivermectin. AB - This study assessed changes in circulating parasite antigen levels after diethylcarbamazine (DEC) and ivermectin treatment of bancroftian filariasis to determine effects of these drugs on adult Wuchereria bancrofti in vivo. Thirty adult Haitians with microfilaremia were treated with 1 mg of ivermectin to reduce counts of microfilariae. Later, subjects were treated with either one or two 200 micrograms/kg doses of ivermectin or with 12 daily 6 mg/kg doses of DEC. Macrofilaricidal activity of these drugs was indirectly monitored by measuring circulating W. bancrofti antigen by EIA. Antigen levels fell by 75% after DEC and by 34% after ivermectin. These results suggest that low-dose ivermectin treatment followed by a standard course of DEC is a more effective macrofilaricidal regimen for W. bancrofti than either of the multidose ivermectin regimens used in this study. PMID- 1894944 TI - Discordance between primer pairs in the polymerase chain reaction for detection of human immunodeficiency virus type 1: a role for taq polymerase inhibitors. PMID- 1894945 TI - Amplification of human immunodeficiency virus provirus from cerebrospinal fluid: results of long-term clinical follow-up. PMID- 1894946 TI - Lipoprotein 90K in human immunodeficiency virus-infected patients: a further serologic marker of progression. PMID- 1894948 TI - Secretory diarrhea and candidal overgrowth: cause and effect? PMID- 1894947 TI - Centers for Disease Control Group M-6: a cause of destructive endocarditis. PMID- 1894949 TI - Failure of ketoconazole maintenance therapy for disseminated coccidioidomycosis in AIDS. PMID- 1894950 TI - Distinguishing pathogenic isolates of Entamoeba histolytica by polymerase chain reaction. PMID- 1894951 TI - Failure of breast-feeding to prevent Cryptosporidium infection in a primate model. PMID- 1894952 TI - Can in vivo surveys on the chemosensitivity of Plasmodium falciparum still be done in tropical Africa? PMID- 1894953 TI - Pentoxifylline in cerebral malaria. PMID- 1894954 TI - Chloroquine inhibits tumor necrosis factor production by human macrophages in vitro. PMID- 1894955 TI - Infectious diseases in China. PMID- 1894956 TI - The role of cytokines in oncology. AB - The availability of sufficient quantities of recombinant human cytokines and promising preclinical data have led to their introduction into clinical trials. Cytokines have potential as new therapeutic agents in a variety of hematological disorders as well as in solid tumors. Only a few of the still increasing number of these glycoprotein hormones have been studied in humans so far, either as single agents or in combination with chemotherapy and other cytokines. Their clinical effects, beneficial role in supportive care, and use in the treatment of certain cancer patients are reviewed. PMID- 1894957 TI - Hematopoietic growth factor receptors. AB - The molecular cloning for most of the hematopoietic growth factor receptors has been achieved over the past few years and revealed that they can by assigned to two discrete receptor families, namely the hematopoietic growth factor superfamily (HRS) and the receptor tyrosine kinase family (RTK). The members of the HRS, including granulocyte-macrophage colony-stimulating factor receptor (GM CSF-R), interleukin 3 receptor (IL-3-R), granulocyte CSF receptor (G-CSF-R) and erythropoietin receptor (Epo-R), share a common binding domain and the absence of a tyrosine kinase domain in their cytoplasmic portion. In some cases (e.g., GM CSF-R), the high-affinity receptor structure is obtained through the association of the low-affinity binding chain (alpha chain) with an accessory protein (beta chain). It is conceivable that this protein might also represent the common subunit shared by GM-CSF-R and by IL-3-R when they are co-expressed to form the putative GM-CSF-R/IL-3-R complex. Although tyrosine phosphorylation following ligand receptor activation seems to be a common event in the HRS, its role in the signal transduction mechanisms is unknown. Due to the structural analogies among the members of this family any new insight into one particular receptor member, such as its subunit structure and its signal transduction pathways, will be generalizable to the other family members. The subclass III of the RTK family, including the CSF-1-R and c-kit, is characterized by an additional insert into the kinase domain that recognizes and binds protein substrates. Ligand induced activation of the kinase domain and its signaling potential are mediated by receptor oligomerization which stabilizes interactions between adjacent cytoplasmic domains and leads to activation of kinase function by molecular interaction. Interestingly, the receptors included in this subclass are the products of well known cellular proto-oncogenes. A large variety of structural alteration found in receptor-derived oncogene products may lead to constitutive activation of receptor signals that, consequently, result in the subversion of the mechanisms controlling the cell growth. PMID- 1894958 TI - [Intracoronary thrombolysis and coronary artery bypass grafting--the favorable results of combined revascularization for myocardial infarction]. AB - The results of coronary artery bypass grafting performed in 10 patients receiving intracoronary thrombolysis were reviewed. There were 9 males and 1 female. The mean age was 60.5 years old ranged from 41 to 77 years old. The obstructed vessels were the left anterior descending artery: 6, the right coronary artery system: 1, both the left anterior descending artery and the right coronary artery system: 1, and the left main trunk: 2. All patients survived after successful recanalization with constrict monitoring, systemic heparinization and oral anti coagulants. All the patients received elective coronary revascularization for the occluded vessels and the other vessels, and the mean number of distal anastomoses was 2.8 ranged from 1 to 4. There were no operative deaths, no perioperative myocardial infarction, no use of balloon pumping or no serious complications. Symptomatic relief was obtained 10 of 10 patients. Left ventriculographic studies showed significant improvement in regional and global left ventricular ejection fraction after coronary artery bypass grafting compared with after thrombolysis. In conclusion, successful thrombolysis for acute myocardial infarction reduces early mortality. Additional coronary artery bypass grafting is beneficial for not only definite correction of the underlying arteriosclerotic lesion, but also improvement of left ventricular function. PMID- 1894959 TI - [Pressure monitoring of the coronary sinus during retrograde cardioplegia]. AB - Though the retrograde perfusion via the coronary sinus is a useful way of myocardial protection for more complicated cardiac surgery, coronary venous injury and inadequate preservation of the right ventricle were considered to be disadvantageous. In order to deal effectively with these problems we made a 3-way balloon catheter (Retro-Higami type 12 Fr) and evaluated the importance of monitoring the perfusion pressure in the coronary sinus in 214 patients. The mean perfusion pressure during retrograde cardioplegia infused by a pump was 29.4 +/- 9.1 mmHg, and had significant relation to the left ventricular mass weight (LVMW) which was calculated by UCG method. High perfusion pressure above 40 mmHg, which could have induced coronary venous injury, was noticed in 24 patients, but proper countermeasures could avoid venous injury completely. In 16 of those the high perfusion pressure was due to inadequate position of a tip of the catheter, and in other 8 it was due to relatively high flow rate of cardioplegic solution to LVMW. Twenty-eight patients showed low perfusion pressures below 20 mmHg, due mainly to the leakage from the orifice of the coronary sinus. The coronary sinus pressure during continuous gravity retroperfusion which was 9.2 +/- 2.6 mmHg seemed to bring optimal delivery of cardioplegic solution to the myocardium. On the basis of the results obtained from this clinical study we conclude that the monitoring of coronary sinus pressure during retroperfusion is useful not only to avoid coronary venous injury but to maintain adequate perfusion. PMID- 1894960 TI - [Reevaluation of the unilateral pulmonary artery occlusion test--hemodynamics after lobectomy and pneumonectomy for lung cancer]. AB - After lobectomy, it is recognized that functional as well as absolute reduction occurs in residual lobes of the operated side. So whether lobectomy is indicated or not is determined by the same criteria as those for pneumonectomy, namely, by the unilateral pulmonary artery occlusion (UPAO) test. However, is it really appropriate to use the same criteria for both lobectomy and pneumonectomy? To answer to this question, in patients with lung cancer we compared the hemodynamics after lobectomy (13 cases) and pneumonectomy (14 cases) with that at the UPAO test. After pneumonectomy, the mean pulmonary arterial wedge pressure (mPWP) was significantly lower than that on the preoperative day and at the test. It seemed that hypovolemic change occurred in the hemodynamics after pneumonectomy. After pneumonectomy, the pulmonary arteriolar resistance index (PARI) was significantly higher than the preoperative value. It was the same as that as at the time of the UPAO test. The total pulmonary vascular resistance index (TPVRI) at the time of the test was significantly higher than the preoperative value, but the TPVRI after pneumonectomy was not significantly higher. The TPVRI tended to decrease after pneumonectomy, compared to the value predicated by the test. These results indicated that some of the cases judged inoperable on the basis of the UPAO test might be operable. On the day of lobectomy, the PARI was significantly higher than the preoperative value, but significantly lower than that at the time of the test. The cardiac index (CI) was significantly higher and the mPWP was significantly lower than each preoperative value.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1894961 TI - [Reoperation of primary tissue failure of bioprosthesis in the mitral position]. AB - The surgical results of 38 patients who underwent reoperation for primary tissue failure of bioprosthesis in the mitral position between May 1982 and June 1990 were analyzed to determine the risk factors affecting the hospital mortality. The type of bioprostheses requiring reoperation were Hancock valve in 21 patients, Liotta valve in 15 patients and Mitroflow valve in 2 patients. Twenty-five preoperative and perioperative variables were collected and analyzed by univariate statistics using chi 2 test or Student's test. Four of thirty eight patients died postoperatively in the hospital, yielding an overall mortality of 10.5%. The causes of hospital mortality were low output syndrome in 2 patients and multiple organ failure in 2 patients. By univariate analysis, male, NYHA IV class, prosthetic stenosis, hepatic failure, renal failure, and pulmonary failure were risk factors predictive of high hospital mortality. In spite of recent improvement of surgical technique and myocardial protection, the hospital mortality of patients with NYHA IV class and advanced organ failure still remains unacceptable. Therefore, it is essential to perform reoperation for primary tissue failure of bioprosthesis before severe myocardial decompensation occurs. To accomplish this goal, patients with bioprosthesis who survived beyond the certain time should be followed periodically using echocardiogram. PMID- 1894962 TI - [Timing of operation based on evaluation of postoperative left ventricular contractility in patients with aortic regurgitation]. AB - To evaluate the effect of aortic valve replacement on left ventricular function in aortic regurgitation, the ratio of end-systolic wall stress to end-systolic volume index (ESS/ESVI) and standard ejection phase indexes of left ventricular function were measured angiographically in 29 patients with isolated, chronic aortic regurgitation before and an average of 26 months after aortic valve replacement. The patients were divided into three groups based on preoperative left ventricular volume at end-systole (ESVI); 12 patients had an ESVI smaller than 100 ml/m2 (group I), 11 had an ESVI of 100 to 200 ml/m2 (group II) and 6 had an ESVI greater than 200 ml/m2 (group III). Postoperatively, end-diastolic volume index and ESVI decreased markedly in all 3 groups and end-systolic stress also decreased. Systolic pump performance assessed as ejection phase indexes improved in all groups with group I and group II showing normal or near-normal ejection fraction, while group III still had a depressed ejection fraction. Left ventricular contractile function as assessed by ESS/ESVI improved significantly in each group postoperatively. After operation, group I patients had normal values. However, both group II and group III still had a subnormal ratio, suggesting a depressed contractility despite normal or near normal systolic pump performance. Surgical correction for aortic regurgitation should be considered before a preoperative ESVI exceeds 100 ml/m2, to preserve postoperative left ventricular contractility. PMID- 1894963 TI - [Surgical repair of descending aortic aneurysms--experience in 100 patients under partial cardiopulmonary bypass]. AB - Between 1975 and 1986, 100 consecutive patients with aneurysms of the descending thoracic (84 cases) or the thoracoabdominal aorta (16 cases) underwent surgical repair. Intraluminal graft inclusion procedure was employed in principle under routine circulatory support with partial cardiopulmonary bypass. In this study, overall surgical results were reviewed, and multiple factors discriminately contributing to early results were assessed using multivariate analysis (quantification theory type II) to determine if this therapeutic modality is pertinent. Fifty-five patients had non-dissecting, 42 had dissecting aneurysms and 3 had pseudoaneurysms. Seventeen patients were treated in the emergency setting. Perioperative or early deaths occurred in 14 patients. Mortality increased with advanced age (greater than 70 years) and with atherosclerotic aneurysms, especially when they involved the entire thoracic or thoracoabdominal aorta. Operative mortality during the last 5 years of the study was 9.3%: significantly lower than the figure in the first 5 years of 28% (p = 0.0198). The incidence of renal dysfunction (7.4%) or paraplegia (2.1%) was not related to aortic cross-clamp time, and both were markedly decreased to 3.8% and 0.0%, respectively, when the cases of thoracoabdominal aneurysms were excluded. There were 8 cases of exploration for postoperative hemorrhage and 6 cases of pulmonary insufficiency requiring more than 3 days of mechanical ventilation. Prolonged bypass time was a discriminative risk factor for these two complications. Cerebral vascular accidents developed in 5 patients, three of them terminated in death. In spite of partial bypass, the factors of advanced age, atherosclerosis, and cross-clamp on the aortic arch were defined responsible for brain stroke.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1894964 TI - [Clinical experience with omniscience and omnicarbon prosthetic heart valves]. AB - Omniscience valves were implanted in sixty-two patients. Twenty-eight of these patients underwent aortic valve replacement (AVR), 15 had mitral valve replacement (MVR) and 8 had aortic and mitral valve replacement (DVR). Post operative events occurred in nine (5.9%/patient year) of the AVR group, in three (1.7%/patient year) of the MVR group and in three (5.4%/patient year) of the DVR group. The actuarial freedom from all events at five years in the AVR, MVR and DVR was 74 +/- 8%, 88 +/- 6%, 67 +/- 16%, respectively. Cardiac death occurred in four (2.5%/patient year) of the AVR, one (0.6%/patient year) of the MVR and two (3.6%/patient year) of the DVR. The freedom at five years in the AVR, MVR and DVR was 88 +/- 6%, 96 +/- 4%, and 77 +/- 14%, respectively. Valve-related complications were noted in four patients. Post-operative cerebral hemorrhage was seen in three of the AVR. Maximum opening angle of the Omniscience valve was 39.1 +/- 4.5 degrees at the aortic position and 44.6 +/- 9.7 degrees at the mitral position. Omnicarbon valves implanted in ninety-five patients, fifty-eight of these patients underwent AVR, 24 had MVR and 13 had DVR. Events occurred post operatively in four (2.6%/patient year) of the AVR group, in three (12.2%/patient year) of the MVR group, but in none of the DVR group. The freedom at five years was 89 +/- 6% in the AVR and 84 +/- 8% at three years in the MVR. Post-operative cardiac death occurred in one (0.7%/patient year) of the AVR and in two (8.1%/patient year) of the MVR.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1894965 TI - [Surgical treatment of coexistent aortic, peripheral vascular and coronary disease]. AB - To determine the priority of the surgical treatment of coexistent aortic and coronary disease (CAD), we reviewed 19 cases of aortic aneurysm combined with severe coronary lesions who underwent operation from Jan, 1984 to Aug, 1989. There were 15 cases of abdominal and 4 cases of thoracic aneurysm. All patients had graft replacement for the aneurysm and 12 patients had elective aortocoronary bypass surgery (CABG), one had percutaneous transluminal coronary angioplasty and 6 received medical treatment for CAD. In 6 cases, CABG preceded abdominal aneurysm operation. In 3 cases of ascending thoracic aneurysm, simultaneous coronary and aortic operation were performed. There were no early and late operative death. In an attempt to reduce perioperative myocardial infarction which is one of the most frequent complications of aneurysmal operation, we performed routine coronary angiogram before operation. In 104 patients considered for elective aortic and peripheral vascular disease, coronary angiogram were performed. The incidence of coexistent coronary artery disease in peripheral vascular and aortic disease were 46.1%. The incidence of multiple vessel CAD in patients with aortic and peripheral disease were high. Our surgical strategy for coexistent aortic, peripheral vascular and coronary disease is basically staged operation and simultaneous operation are performed only in ascending and proximal arch aneurysm. PMID- 1894966 TI - [Surgical treatment of acute ascending dissection--a simplified operative method]. AB - Primary anastomosis for acute ascending aortic dissection was performed in 8 patients. Primary anastomosis included resection of the intimal tear where applicable, a circumferential suture line in the ascending aorta at the site of the tear, and wrapping of the anastomosis of the ascending aorta with Dacron vascular prosthesis. The aortic valve was resuspended in 1 of 6 patients associated with aortic regurgitation. In 4 patients, aortic regurgitation disappeared postoperatively. Two patients show minor non-progressive valve regurgitation. Two of 8 patients died early postoperatively. There was no late death and dilatation of the aortic root in the follow-up period of mean 27 months. On the basis of these results, we believe that primary anastomosis is a simpler and safer operative method for acute dissection of the ascending aorta. PMID- 1894967 TI - [Surgical treatment and their long-term results of the ascending aortic lesions involving coronary arteries]. AB - Seventeen patients underwent surgical treatment of the ascending aorta, aortic valve, and coronary artery as well. Diagnosis of 13 patients were annulo-aortic ectasia, 3 had dissecting aneurysm (type I: 2, type II: 1), and one had supra valvular aortic stenosis. In annulo-aortic ectasia, Bentall's method was carried out in 11 cases, and Cabrol's operation was performed in 3, one of the latter group had received Bentall's procedure 4 years prior to the second operation. One patient died of acute myocardial infarction 3 days following operation, who had severe stenosis of the left anterior descending artery not detected by preoperative angiography. During long-term follow up, 2 patients died of cardiac failure. Three patients had dissection of the ascending aorta and coronary artery (right coronary artery: 2, left coronary artery: 1). The aorta was reconstructed, aortic valve was replaced, and coronary artery was revascularized with saphenous vein graft. They have been alive and well up to post operative 6 years. Right coronary ostioplasty as well as aortic valve replacement and extended aortoplasty were attempted in one patient with Williams' syndrome. This patient had been well until sudden death which occured 11 months after the operation. PMID- 1894968 TI - [Case report of right ventricular myxoma]. AB - A 14-year-old woman was admitted to our hospital due to heart murmur. Loud systolic murmur at the forth intercostal space was altered its intensity by patient's posture. The chest roentgenogram showed normal cardiovascular silhouette. The electrocardiogram revealed normal sinus rhythm without right bundle branch block. The echocardiography and cineangio-cardiography proved a tumor in the right ventricle. Right heart catheterization showed pressure gradient for 35 mmHg between the right ventricle and the pulmonary artery. At surgery, the tumor was excised with the full thickness of the anterior right ventricular wall. The tumor was cardiac myxoma with 15 g of weight. The patient's postoperative course was uneventful. PMID- 1894969 TI - [Biventricular assist support using centrifugal pump in cardiogenic shock following coronary bypass grafting--a case report of long survival]. AB - Biventricular assist support (BVAS) with centrifugal pump was used for the treatment of 48 y/o male patient with cardiogenic shock following coronary bypass surgery. Assist flow was 2 to 4 l/min in LVAS and 2 to 3 l/min in RVAS. RVAS was weaned in the fourth postoperative day and LVAS in the sixth. Cerebral infarction developed in the weaning period of LVAS. Post operative examination revealed good right and left ventricular function. Patient was well and returned to full work in a two years and two months after surgery. BVAS may be useful for the treatment of severe biventricular failure associated with stunned myocardium. PMID- 1894970 TI - [Mediastinal hematoma due to thymoma hemorrhage--a case report]. AB - A 70-year-old man came to our hospital complaining mainly of acute dyspnea. A chest X-ray, echocardiogram, and chest CT showed a mediastinal mass, and pericardial and pleural effusions. A thoracotomy revealed a cystic tumor along the thymus. The tumor contained bloody fluid, coagula, and fibrin calculi. Rapid specimens showed no tumor cells and the hematoma was assumed to have been caused by the thymus. Therefore, a thymectomy was performed and as much of the hematoma as possible was removed. After the operation, a careful pathological examination revealed a thymoma with a diameter of about 7 mm. In addition, coagula and fibrin calculi contained some tissue from the thymoma, and the diagnosis was made that a mediastinal hematoma had formed due to hemorrhage from the thymoma. Several cases of mediastinal tumor of cyst hemorrhages in the thorax have been reported. However, only a few cases of thymomal hemorrhages in the thorax have been reported; one case each of mediastinal hematoma, hemothorax, and cardiac tamponade. Great care is necessary when dealing with atraumatic mediastinal hematomas if malignant tumors such as thymoma are present. PMID- 1894971 TI - [A case of unusual branching and aberrant course of the segmental vein (V2) in the upper lobe of the right lung]. AB - Two right pulmonary veins emptying into the left atrium is the normal state. We describe a case observed at operation in which three pulmonary veins were present on the right side and emptied into the left atrium; a third vein arised from the dorsal part of the upper lobe and followed an abnormal extrapulmonary course. Right lower lobectomy and mediastinal lymph node dissection were carried out for a 73-year-old male with lung carcinoma. At operation, an aberrant branching vein arising from the upper lobe descended dorsally to the right main bronchus and emptied into the left atrium at the middle point between carina and inferior pulmonary vein. The intermediate bronchus lay between the anomalous vein and superior pulmonary vein. Conventional tomogram, CT scan and pulmonary angiogram showed that pulmonary arteries and bronchi were normal in their pattern of branching and distribution, and that the anomalous vein observed at operation was comprised of V2a and V2b according to the system of naming on Yamashita's. Infrequent variations of pulmonary veins are to be kept in mind to that operation may be performed in safety. PMID- 1894972 TI - [A case of invasive thymoma displaying endobronchial and endocaval polypoid growth]. AB - The hens' egg-sized tumor connecting from anterior mediastinum to the hilus by chest radiography and chest CT was noted in a 63 year old female who complained of facial swelling and cough. The defect of the thumb tip-sized shadow was noted in the superior vena cava by superior vena cavography, and polyp covered with white coating obstructing the right apical bronchus was noted by fibrotic bronchoscopy, and malignant finding was obtained by biopsy of this polyp. After midsternotomy, a mass invaded to the superior vena cava and the right upper lobe was resected, and then superior vena cava was reconstructed by using supported polytetrafluoroethylene. The resected specimen revealed that the tumor extended not only to the pulmonary parenchyma with polypoid growth into the lumina of bronchi but also to the superior vena cava with polypoid growth. The patient was discharged at the postoperative radiotherapy with 40 Gy, and he is still alive free from the disease 3 years and 11 months after operation. PMID- 1894973 TI - [Congenital bronchomalacia of left main bronchus combined with lobar emphysema, pectus excavatum and right aortic arch--a case report]. AB - One-year-old girl was admitted because of recurrent pneumonia and pectus excavatum. Chest X-ray showed hyperlucency at the upper lung field and infiltrated shadow at the lower field of the left lung. Bronchoscopy and bronchograms revealed marked collapse in a long segment of the left main bronchus during expiration. CT scan showed an emphysematous change and a giant bulla of left lung. Angiogram showed right aortic arch. Sternoturnover was performed at 5 years of age for pectus excavatum. After 10 months, left pneumonectomy was performed for bronchomalacia and lobar emphysema. Pathologic findings of the bronchus revealed that the rings were flattened, while the cartilage was microscopically normal. PMID- 1894974 TI - [A severe respiratory distress in a new born infant with double aortic arch without cardiac anomalies]. AB - A 39-day-old girl underwent operation for double aortic arch. She required endotracheal intubation at 23-day-old because of severe respiratory distress. Echocardiography, esophagography and angiocardiography revealed double aortic arch without other cardiac anomalies. At the operation the lesser arch and ductus arteriosus were divided. Soon after the operation her respiratory distress disappeared and fiberbronchoscopic examination showed rapid recovery of the deformed trachea. PMID- 1894975 TI - [A case of mitral stenosis associated with cardiac sarcoidosis and left ventricular aneurysm]. AB - We report a rare case of mitral stenosis associated with cardiac sarcoidosis and left ventricular aneurysm. A 60-year-old female was admitted with complaint of palpitation and dyspnea on exertion. Chest X-ray revealed cardiomegaly and pericardial calcification, but no bilateral hilar lymphadenopathy. Electrocardiogram showed various arrhythmia. Coronary angiography showed no stenosis in any coronary arteries. Cardioangiogram showed left ventricular aneurysm at the apex and mitral stenosis. Laboratory findings showed no evidence of sarcoidosis. Open mitral commissurotomy and left ventricular aneurysmectomy was performed. Pathological findings of the myocardium showed a remarkable degenerative change and a granulomatous inflammation. Postoperative biopsied specimens of right scalene lymph nodes revealed sarcoid reaction. The postoperative course was satisfactory, but arrhythmia remained. The patient was treated with steroids and pacemaker implantation. She has been doing well for 2 year postoperatively. An operative case of mitral stenosis associated with cardiac sarcoidosis and ventricular aneurysm due to sarcoidosis is very rare and the prognosis in patient is very poor usually. PMID- 1894976 TI - [A case of a large invasive thymoma successfully treated by using a combination of artery infusion of CDDP and operation]. AB - A 21-year-old male was admitted with SVC syndrome. Chest X-ray film showed an abnormal density on the upper mediastinum, that was recognized thymoma on the needle aspiration specimen. The large tumor, which extensively infiltrated the surrounding tissues (SVC, the right brachiocephalic vein, bilateral lungs and the pericardium) led us to choose preoperative chemotherapy. CDDP (cisdiammin edichloroplatinum) was infused through the right IMA (internal mammary artery). After obtaining the major response the tumor mass was resected with adjacent structure accompised vessels reconstructions. Histological examination revealed totally necrosed tissue. Three years after initiation of therapy, the patient is doing well. The therapy with CDDP injection into selective IMA for invasive thymoma before operation was considered to be very useful utilized. PMID- 1894977 TI - [Recurrent thymic carcinoid tumor--report of a case]. AB - A previously operated 62-year-old male with recurrent thymic carcinoid tumor was reported. This patient underwent resection of the thymic carcinoid tumor through left thoracotomy 7 years ago. Although the postoperative clinical course was uneventful, an anterior mediastinal tumor on the patient's chest was discovered after an X-ray examination due to a traffic accident in July, 1989. With the diagnosis of recurrent thymic carcinoid tumor, he underwent an excision of the anterior mediastinal tumor and residual thymus. He also underwent partial resection of the pericardium, mediastinal pleura, and left upper lobe of the lung. 42 cases with thymic carcinoid tumor that have been reported in the Japanese literature were reviewed. A perusal in the relevant literature suggested that total thymectomy was advisable because partial thymectomy was associated with a high risk of local recurrence and metastases. PMID- 1894978 TI - [Successful surgical treatment of a case of corrected transposition in situs inversus with associated anomalies]. AB - A 33-year-old female with corrected transposition (situs inversus) with ventricular septal defect (VSD), atrial septal defect (ASD), and pulmonary stenosis (valvular and subvalvular) was operated successfully. Closure of ASD and infracristal VSD was performed through right atrial approach. In order to get complete exposure of VSD, a part of anterior leaflet of mitral valve was detached temporally. An external conduit was interposed between the morphologic left ventricle and the main pulmonary artery to relieve pulmonary stenosis. Postoperative course was uneventful except a transient complete heart block for a day. Several technical aspects of the radical operation were discussed including VSD closure method to avoid damaging the atrioventricular conducting tissues and reconstructive procedure of morphological left ventricular outflow. PMID- 1894979 TI - [Surgical treatment of the aortic arch dissection--a report of two cases operated by partial brachiocephalic perfusion, and open aortic anastomosis]. AB - Two patients underwent aortic arch replacement for the dissecting aneurysm of the aorta using a simplified cardiopulmonary bypass (CPB) technique with partial brachiocephalic perfusion, moderate systemic cooling (22 degrees to 23 degrees C), and open aortic anastomosis were reported. The partial brachiocephalic perfusion was accomplished by perfusion to the right axillary artery using separate pump. Open distal anastomosis was performed under low flow hypothermic perfusion of the lower body during selective perfusion to the brain. Cardiopulmonary bypass and partial brachiocephalic perfusion time were 170 minutes, and 30 minutes in one case, and 207 minutes, 56 minutes in the other case. Both patients survived operations, and there were no postoperative strokes, and neurological complications. On the basis of these results, we discussed about supportive methods for aortic arch surgery. PMID- 1894980 TI - [A case of bronchial mucoepidermoid carcinoma in a 8-year-old child treated with right upper sleeve lobectomy]. AB - A 8-year-old boy was admitted to our hospital with complaint of cough and abnormal shadow on chest X-ray. Bronchoscopy and biopsy revealed a bronchial mucoepidermoid carcinoma, which obstructed right main bronchus. Right upper sleeve lobectomy was performed. The histological examination revealed a low grade malignant mucoepidermoid carcinoma. There were no metastases in the mediastinal lymph nodes. He has been healthy with no evidence of recurrence during 4 years after operation. PMID- 1894981 TI - [Therapeutic guide line for hemoptysis]. AB - We report the result of treatment for thirty-two patients whose chief complaint was hemoptysis and represent the therapeutic guide line for hemoptysis. In thirty two cases, there were twenty men and twelve women and average of age was fifty two years old. Twenty-nine of them were chronic lung diseases such as tuberculosis and bronchiectasis and only three cases have malignant tumors. Two of them recovered with conservative therapy and bronchial arteriography (BAG) have been performed in thirty patients in order to determine the bleeding foci, BAG was failed in two cases, but these two cases have been recovered with following up, BAG was succeeded in twenty-eight cases and twelve cases of them could not been determined the bleeding foci by angiography and could be controlled using hemostatic and antibiotic agents. Embolization of bronchial arteries with gelatin sponge have been performed in sixteen cases and made success in eleven cases. In ten of these cases, BAE was effective less than two times. Only one of silicosis with restrictive lung function was considered contraindication of surgery and recovered by three times of BAE. Four cases of five uneffective BAE (rebleeding after two times of BAE) have been treated by operation in good course. But one case complicated with WPW syndrome has died because of aspiration pneumonia without operation. In our institute, the rate of operation for hemoptysis was low as 13% of thirty-two cases. In order to consider the indication of surgery, bronchial arteriography was essential to determine bleeding foci and BAE was effective in over 80% of hemoptysis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1894983 TI - [Conotruncal repair of tetralogy of Fallot under 2 years old]. AB - From October 1985 to September 1990, a repair within the conotruncal portion of the right ventricle-Conotruncal repair-was used for the primary repair of consecutive 34 patients with tetralogy of Fallot under the age of 2 years. There were three summarized points of this maneuver: the first was non-use of the tricuspid septal leaflet for closure of the ventricular septal defect, the second was short patch infundibuloplasty with a large monocusp, and the last was total resection of the infundibular septum. Length of the patch infundibuloplasty was just 30% of the right ventricle length according to our formula: 30% of RV (cm) = 1.28 X BSA (m2) + 1.10. The VSD patch was placed between the pulmonary annulus and the ventricular septal crest, consisting of the membranous flap and the posterior extension of the trabecula septomarginalis. The right ventricular (RV) to systemic arterial pressure ratio was 0.49 +/- 0.15 (N = 33) and central venous pressure was 10.2 +/- 1.9 cmH2O (N = 33) six hours after ICU admission and 8.4 +/ 1.5 cmH2O (N = 7) 18 days after operation. RV end-diastolic volume showed no increase after operation: 105 +/- 31 before repair to 104 +/- 23% of Normal after repair in the same patients. Post-operative intubation period was 14 +/- 8 hours and hospital admission period was 17 +/- 6 days after operation. All patients were in sinus rhythm. The 28% of patients showed incomplete right bundle branch block (RBBB) and other 28% of patients showed complete RBBB.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1894982 TI - [Biological specificity of the neonate and infant heart, with reference to selenium and glutathione peroxidase--the study to clarify the cause of vulnerability of neonate and infant heart]. AB - Selenium (Se) is known to be an integral part in glutathione peroxidase (GSHPx). There are some reports serum Se levels are lower in infants than in adults and GSHPx activity is parallel to Se levels. There may be reasons why myocardial reperfusion injury occurs more easily in infants than in adults by reperfusion of ischemic myocardium. Serum and myocardial Se levels and GSHPx activity in experimental rats were measured to clarify the vulnerability of infant heart. Wistar rats were divided into three groups. First, infant rats 8-12 days after birth (infant rats), second, adult rats fed Se-deficient diet for two months (Se deficient rats), and third, adult rats fed normal diet for two months (control rats). Serum Se levels, serum GSHPx activity and myocardial GSHPx activity in both infant and Se-deficient rats were significantly lower than that in control rats (p less than 0.01). However myocardial Se levels in infant rats were significantly higher than that in both Se-deficient and control rats (p less than 0.01). The lipid peroxide levels in heart mitochondria of Se-deficient rats were significantly higher than that in control rats (p less than 0.01). These results suggest that in infant heart Se does not manifest an effective function for a integral part of GSHPx despite its high level, its reason is not clear, and this phenomenon generates more oxygen-derived free radicals after reoxygeneration of the ischemic myocardium. PMID- 1894984 TI - [The effects of coronary revascularization in patients with severe left ventricular dysfunction]. AB - To evaluate the operative risk of coronary diseased patients who had severe left ventricular dysfunction, we retrospectively reviewed the cases of 798 patients who had received A-C bypass surgery at Juntendo University between Jan. 1984 and Dec. 1989. The patients with severe left ventricular dysfunction (Ejection Fraction less than 30%) (Group-A, n = 9) were compared with the patients with moderately impaired left ventricular function (E.F. 30%-40%) (Group-B, n = 28) and normal left ventricular function (E.F. greater than or equal to 50%) (Group C, n = 34). The mean E.F. were 21.56 +/- 3.72% in Group-A, 34.28 +/- 3.17% in Group-B, 64.19 +/- 12.02% in Group-C. There were no differences between the 3 groups with regard to Cardiac Index, LVEDP, number of diseased vessels, number of grafts, aortic cross clamp time and cardio-pulmonary bypass time. The percentages of patient who needed catecholamines support in postoperatively were 77.8% in Group-A, 46.4% in Group-B and 61.8% in Group-C. There were no operative and hospital deaths in each of the 3 Groups, whereas 2 patients of Group-A died later of noncardiac disease. We propose that patients with severe left ventricular dysfunction (15 less than or equal to EF, less than 30%) benefit from CABG surgery with low risk, and that each left ventricular E.F., Cardiac Index or LVEDP alone were less significant predictors of operative results as measured by preoperative left ventricular function. PMID- 1894985 TI - [The adequate diagnostic criterion of mediastinal lymph node size for detection of metastasis in primary lung cancer]. AB - The size of lymph node is one of the most important factor in evaluation of lymph node metastasis in lung cancer. The most appropriate size for detecting lung cancer lymph node metastasis was studied by 2403 dissected lymph nodes in 75 operated cases of lung cancer. From the result of Receiver Operating Characteristic (ROC) curve analysis, long-axis diameter of the lymph node showed higher accuracy of diagnosis of metastasis than short-axis diameter. Metastasis of squamous cell carcinoma was diagnosed more accurately than that of adenocarcinoma. The most adequate threshold for detection of metastasis in squamous cell carcinoma was 10 mm in long-axis diameter with sensitivity of 73.8% and specificity of 78%. On the other hand, that of adenocarcinoma was 7 mm in long-axis diameter with sensitivity of 65.7% and specificity of 55.9%. That threshold value of adenocarcinoma was approximate to the value of normal lymph node size in the mediastinum. It was suggested that the size for detection of lymph node metastasis was depended upon histological type, and detection of lymph node metastasis in adenocarcinoma was extremely difficult. PMID- 1894986 TI - [Left atrial thrombus in the early postoperative period after mitral valve replacement]. AB - Left atrial thrombus after mitral valve surgery is believed to be relatively rare. However, we previously reported on cases of left atrial thrombus (LAT) with spontaneous regression in the early postoperative period. Forty two patients who underwent mitral valve replacement were studied using computerized tomography (CT). Early postoperative LAT was found in 11 patients out of 42 (26.2%); all of whom had an uneventful postoperative course. The mean preoperative atrial diameter in the LAT group (81.4 mm) was greater than that in the non-LAT group (57.0 mm). This was the most decisive factor significant enough for discriminating between the two groups. Other factors, including age, sex, length of symptoms, preoperative NYHA classification, cardiac rhythms, preoperative cardiac index, duration of cardiopulmonary bypass, type of artificial valve used, duration of intubation and period prior to anticoagulant therapy were not significant. From March 1988, 10,000 U/day of heparin was administered to 20 of the 42 patients. LAT developed in 2 cases (10%). Of the 22 patients who did not accept heparin therapy, 9 (41%) developed LAT. Of the 11 patients having postoperative LAT, 6 were treated by fibrinolytic therapy (urokinase plus heparin). A decrease in thrombus size was observed in 3 cases, and no change in the other 3. Postoperative anticoagulant therapy with warfarin and dipyridamole was administered to all 11 LAT patients, in 8 cases, LAT disappeared for 3 to 42 months period. We therefore conclude as follows: 1) The incidence of early postoperative LAT was 26.2% (11/42). 2) Postoperative thrombus was more likely to occur in the left atrium with a large diameter. 3) Heparin dose of 10,000 U/day seemed to be an effective prophylactic therapy for LAT. 4) Fibrinolytic therapy with urokinase and heparin was not always favorable in LAT cases. 5) In 8 cases out of 11, LAT was resolved under standard anticoagulant therapy with warfarin and dipyridamole in long-term period. PMID- 1894987 TI - [Surgical treatment of pulmonary atresia with intact ventricular septum in infancy--analysis of right ventricular growth potential after pulmonary valvotomy]. AB - Our surgical experience involving pulmonary atresia with intact ventricular septum (PPA) between the years 1981 and 1989 is reviewed. Twelve infants aged 3 days to 11 months were studied for right ventricular growth potential with angiocardiography and hemodynamics after transventricular pulmonary valvotomy (TVPV). Ten infants were divided into two groups, 5 infants (Group I) were treated with TVPV only, and the other 5 infants (Group II) required additional surgery after the initial operation (TVPV in 2 cases and TVPV with shunt in 3 cases). Post-operative RV growth potential was evaluated with right ventricular index (RVI) based on the tricuspid valve annulus, right ventricular inlet, and right ventricular outlet dimensions, and with tricuspid annular index (TVI) based on the tricuspid valve annulus normalized by aortic diameter. Follow-up (3-69 months after initial operation) studies demonstrated that the RV cavity increased in Group I (RVI of 15.75 +/- 2.92 preoperatively versus 17.00 +/- 1.57 postoperatively, TVI of 3.04 +/- 0.63 versus 3.85 +/- 0.40). In contrast, the RV cavity in Group II demonstrated a lack of growth (RVI of 9.24 +/- 2.60 versus 9.85 +/- 2.76, TVI of 1.46 +/- 0.46 versus 1.70 +/- 0.80). PPA infants with RVI greater than 11 have been treated successfully with TVPV alone, which may maximize the potential for RV growth, but infants with RVI less than 11 have not experienced RV growth + postoperatively and, therefore, have required second intracardiac operations. PMID- 1894988 TI - [Postoperative pulmonary complication and surgical treatment of esophageal cancer in aged patients--evaluation of preoperative risk factors and postoperative management]. AB - Because of the recent improvement in surgical technique and perioperative management, surgical treatment for esophageal cancer has become more extensive and thus even aged poor-risk patients can be operated on. However, transthoracic esophagectomy is still associated with a high rate of postoperative pulmonary complications. We analysed the preoperative findings and postoperative treatment in aged patients. During the decade starting from 1980, 151 patients with esophageal cancer were admitted to our clinic, there were 44 aged patients over 70 years. They were examined for preoperative risk factors associated with multiple organ functions. Our special attention was paid to postoperative pulmonary complications and hemodynamics that were monitored using the Swan-Ganz catheter. In the aged patients, there were highly abnormal finding in preoperative examinations, especially in cardiac, pulmonary and renal functions. Moreover, their cardiac index levels were lower and pulmonary vascular resistance levels were higher than those of the younger group. Postoperative pulmonary complications were induced frequently in the poor-risk patients who underwent transthoracic esophagectomy. However, the patients who were received infusion of dopamine and dobutamine were able to keep hemodynamic balance in the early postoperative period. Most patients with esophageal cancer are relatively old and have often multiorgan dysfunction. Transhiatal esophagectomy is a safe operation that is suitable for the treatment of aged poor-risk patients who can not tolerate thoracotomy. Choice of a surgical procedure for them should be carefully determined according to the systemic preoperative assessment of risk factors. Postoperative fluid therapy and respiratory management should be performed more strictly in the aged patient. PMID- 1894989 TI - [A case report of controlled aortic root reperfusion (CARP) following global myocardial ischemia during surgery for severe mitral stenosis with tricuspid regurgitation]. AB - The use of controlled aortic root reperfusion (CARP) as additional myocardial protection in cardiac surgery has been employed at University of Alabama at Birmingham Since 1986. This technique has been applied to a patient in Japan undergoing mitral valve replacement and tricuspid annuloplasty and favorable results were obtained. The CARP method consists of two consecutive procedures following global myocardial ischemia, that is, terminal warm blood cardioplegic reperfusion and selective controlled coronary perfusion. When the repair was almost completed, the CARP technique was initiated with warm blood (37 degrees C) from an oxygenator, and the initial phase was hyperkalemic (K+ 20 mEq/1, 3 min). [Terminal warm blood cardioplegic reperfusion] This was followed by normokalemic warm blood (without interruption) from the pump oxygenator infused through a cardioplegic needle into the isolated aortic root with the aortic cross-clamp still in place (10 to 20 min). [Selective controlled coronary perfusion] Terminal warm blood cardioplegic reperfusion induced electromechanical quiescence initially which allowed rapid repletion of adenosine triphosphate and improved cardiac function. Selective controlled coronary perfusion with normokalemic warm blood permits necessary and sufficient coronary blood flow following global ischemia even when systemic arterial pressure fell and coronary vascular resistance rose. On considering these two points, we consider that the CARP technique offers excellent myocardial protection in accelerating the recovery of myocardial function following global ischemic damage. The CARP method offers useful assistance in cardiac surgery particularly for patients who have abnormal preoperative cardiac function and who have experienced long periods of global myocardial ischemia. PMID- 1894990 TI - [Recurrent surgery for pulmonary venous obstruction after total correction of TAPVC (IIb)]. AB - A 15-months-old boy underwent the intra-cardiac repair with a glutaraldehyde preserved equine pericardium for total anomalous pulmonary venous connection (Darling's type IIb). Because of rapidly progressive dyspnea, tachycardia and respiratory acidosis, he required emergent reoperation at 234 postoperative days. The pseudointima was thickened heavily and detached from glutaraldehyde-preserved equine pericardium. New channel was created with a piece of EPTFE sheet to prevent obstruction of pulmonary venous flow. However, about four months after second surgery, cough and tachycardia progressed again remarkably. Intra-atrial channel was obstructed between EPTFE sheet and the partition from pulmonary venous orifice to the atrial septal defect in the third operation. The intra atrial channel was enlarged by cut-back method using EPTFE sheet again. His postoperative hemodynamics were satisfactory PMID- 1894991 TI - [A case of quadricuspid aortic valve associated with coronary arterial legion]. AB - A case of quadricuspid aortic valve is reported in a patient with coronary artery disease and abdominal aortic aneurysms. A 54-year-old male who had undergone aortic replacement because of abdominal aortic aneurysms three years before presentation was readmitted due to complaints of angina pectoris and palpitations. Aortography and coronary arteriography revealed severe aortic regurgitation and proximal occlusion of LAD and RCA. Surgical correction consisted of aortic valve replacement with a Bjork-Shilely valve and coronary revascularization of LAD. During the operation, a quadricuspid aortic valve with one smaller and three larger cusps that showed mild myxomatous degeneration without dystrophic calcification and normal coronary arterial orifices were noted. Accordingly, severe aortic regurgitation may have resulted from the dysfunction of congenital malformed cusps and acquired sclerotic coronary disease was the main cause of the chest pain. PMID- 1894992 TI - [A case of pneumothorax in a patient with costal exostosis]. AB - A 21-year-old male was admitted to our hospital complaining of chest pain. He had undergone operations on multiple exostoses of his lower extremities when he was thirteen and fifteen years old. Family history revealed multiple exostoses in his mother and one of his cousins. Chest roentgenograms showed right pneumothorax and a mass arising from the seventh rib in the right lower lung filed. Chest CT revealed that the mass was located in thorax but outside the lung. These findings suggested that the pneumothorax was secondary to the injury of the right lung caused by an exostosis arising from the rib. Upon operation, we found a laceration of the lower lobe and a hard mass the size of a pea protruding from the seventh rib. A small bony spicule was also found to be projecting from the sixth rib. The hard mass and the spicule were resected with a normal portion of the seventh and the sixth ribs. The pathological findings of these bony lesion proved to be consistent with exostosis. The patient's postoperative course was uneventful. This case of pneumothorax caused by an exostosis lacerating the lung is rare. PMID- 1894993 TI - [Percutaneous cardiopulmonary bypass as a bridge to coronary artery bypass surgery in 2 cases of circulatory collapse caused by severe myocardial ischemia]. AB - A closed system of percutaneous cardiopulmonary bypass (PCPB) with centrifugal pump and membrane oxygenator was applied for 2 patients with circulatory collapse caused by acute reclosure of left anterior descending coronary artery after PTCA in case 1 and acute myocardial infarction due to left main coronary artery lesion in case 2. Both patients were brought to operating room under the circulatory support of PCPB and successful coronary artery bypass was performed. Case 1 survived and case 2 died from sepsis due to mediastinitis inspite of satisfactory recovery of cardiac function. PCPB was confirmed as a useful method for emergency circulatory support and a bridge to cardiac surgery in patients with cardiogenic circulatory collapse. PMID- 1894994 TI - [Successful surgical treatment of aortic regurgitation with coronary artery fistula due to blunt chest trauma--a case report]. AB - A Successful repair of aortic regurgitation with coronary artery fistula due to blunt chest trauma is reported. A 17-year-old boy was involved in a motor cycle accident, but there were neither open chest trauma nor rib fracture. On admission diastolic regurgitant musical cardiac murmur was noted. Color doppler echocardiogram showed severe aortic regurgitation. But any cardiac murmur had nerve been noticed before. CAG showed a fistula from the acute marginal branch of the RCA to the RV. But no shunt existed on calculation. The aortic valve was explored under cardiopulmonary bypass. There were a tear in the LCC and a fissure in the RCC. Otherwise the valve tissue appeared normal. The valve was excised and replaced with a integral of 21 mm Bjork-Shiley valve prosthesis. The fistula was left because there were no abnormal findings on the RCA and no significant shunt. The patient is up and well 1 year and 10 months after operation. This is the first report of aortic regurgitation with coronary artery fistula due to blunt chest trauma. PMID- 1894995 TI - [A case report on a double chambered right ventricle (DCRV)--pre- and postoperative responses of the right ventricle to atrial pacing and the isoproterenol tolerance test]. AB - To evaluate the development of an anomalous muscle bandle of the right ventricle (RV) and results of surgical intervention, responses of the RV to atrial pacing and the isoproterenol tests were examined in both the pre- and postoperative periods. Although cardiac output did not increase in proportion to the rate of atrial pacing or the dose of isoproterenol, the pressure gradient through the RV increased abnormally from 38 mmHg to 59 mmHg (atrial pacing) and 116 mmHg (isoproterenol). On the other hand, postoperative evaluation showed normal RV responses in these tests. Since the response of the right ventricle to these tolerance tests in patients with DCRV in pre- and postoperative periods has not been well elucidated, a precise evaluation is reported in this paper. PMID- 1894996 TI - [A treatment of intractable sternal osteomyelitis--significant use of pedicle muscular flaps]. AB - In recent years, the greater omentum of pedicle muscular flap has been used to treat chest wall infection and Sternal Osteomyelitis following cardiac or respiratory surgery. In Japan, however, there has been an increasing number of cases in which neither the greater omentum Nor the rectus muscle can be used due to the comparatively young age of the patient. There are also many cases undergoing abdominal surgery for malignant tumor and bypass surgery of the coronary artery in which the internal thoracic artery (ITA) and gastroepiploic artery (GEA) are used. We studied three such cases; a case of coronary aortic bypass graft (CABG) where ITA from both the right and left sides were used following stomach resection; a case in which CABG and gallbladder resection were carried out simultaneously; and a case of sternal osteomyelitis is years following surgery for ventricular septal defect. All three cases had undergone reconstructive surgery using the pectoralis major muscle or a pedicle muscular flap from the latissimus dorsi muscle. It is estimated that cases of CABG using both the right and left sides of ITA and GEA, cases of the elderly as well as cases of children will continue to increase. Consequently, cases of sternal osteomyelitis in which neither the omentum nor rectus muscle can be used will also increase. Therefore, it is considered that treatment using pedicle muscular flaps from the breast or dorsal area may be very effective. Herein, we report on the choice of treatment and its results. PMID- 1894997 TI - [A case of surgically treated tuberculous aneurysm of descending thoracic aorta with massive hemoptysis]. AB - A tuberculous aneurysm of the thoracic descending aorta was found in a 60-year old female with massive hemoptysis. She had had lung tuberculosis one and half years ago. Computed tomography and aortic angiography revealed saccular type aneurysm at left supradiaphragmatic portion of descending aorta. After antituberculous chemotherapy, the aneurysm was resected under the temporary bypass support utilizing Bio-pump and the aorta was grafted with Dacron prosthesis successfully. The microscopic findings of specimens over the aneurysm and surrounding tissues revealed tuberculosis. The patient is doing well one year after the operation. PMID- 1894998 TI - [Changes in implanted polyvinylformal sponge 35 years after intrapleural sponge plombage]. AB - Successful removal of long-term implanted plombage sponge, its chemical analysis and changes in its mechanical characteristics are reported. A 52-year-old woman who had undergone an intrapleural sponge plombage operation because of tuberculosis, and had since shown an uneventful medical history for 35 years, was referred with a complaint of back skin induration over the previous surgical scar. Resection of the implanted sponge was performed. The ribs attached to the sponge were atrophic and had fused with each other. The sponge had invaded the 6th rib and formed a window-like defect in the fused bony ribcage. The skin induration was found to be caused by hematoma due to damage of the intercostal artery by the sponge. In the sponge, which was made from polyvinylformal, connective tissue infiltration was observed to a depth of 5 mm. The innermost part of the sponge was free from connective tissue infiltration, but the sponge had lost its initial elasticity. PMID- 1894999 TI - [6 cases of contralateral atelectasis immediately after thoracotomy in lateral position--its mechanism and treatment]. AB - Six cases of atelectasis developing in the unopened contralateral lung immediately after thoracotomy in the lateral position were presented, and its cause and treatment were discussed. Atelectasis due to retention of secretion showed various atelectatic X-ray shadows which differed in size by the segment or lobe unit. On the other hand, cases of atelectasis whose occurrence was surmised to be related to the lateral position and anesthesia showed mainly infiltrative shadows which extended from the outer region of the middle-lower lung field to the basal segments of the lung, although some cases were accompanied by atelectatic shadows of various size in terms of the segment or lobe unit. Therefore in order to prevent atelectasis, it is desirable to move sputum by aspiration and appropriately apply ventilation, intermittent pressurization and PEEP, while paying careful attention to the unopened lung. In the treatment of atelectasis, selective endobronchial pressurization using a bronchofiberscope equipped with a cuff was effective. It was also very effective to place an endotracheal tube for ordinary anesthesia near the target bronchus with the aid of a bronchofiberscope and perform selective endobronchial pressurization via that tube. PMID- 1895000 TI - [Mediastinal parathyroid cyst]. AB - A 66-year-old woman, having no complaint, admitted our clinic, because of a mass in the right superior mediastinum detected three years ago on chest X-ray. The operation was performed through the right thoracotomy in December of 1989. The thin-walled cyst located adjacent to the trachea between superior vena cava and back bones, occupied from beneath the innominate artery to the right main bronchus. The tumor (7 x 5 x 5 cm) weighing 80 grams had a smooth surface and contained watery fluid. Histological examination showed a cyst lined a monolayer of cuboidal epithelium. The cyst wall consisted of parathyroid tissue. Mediastinal parathyroid cyst is very rare. Since the first report of DeQuervain, 15 cases have been reported. These reports are reviewed. PMID- 1895001 TI - [The effects of dopamine on the renin-angiotensin-aldosterone system after extracorporeal circulation]. AB - Thirty-one patients underwent elective coronary bypass grafting were studied about the effects of dopamine (DOP) on the renin-angiotensin-aldosterone system (RAAS) for 24 hours after extracorporeal circulation (ECC). All of them had no evident of renal dysfunction nor other complication preoperatively. Patients were divided according to the administration of DOP 5-10 micrograms/kg/min (group D, n = 16) and control group without any catecholamine including DOP (group N, n = 15). Criteria for DOP administration were systolic blood pressure less than 100 mmHg and central venous pressure greater than 15 cmH2O. Hemodynamically no significant difference was observed between the two groups. The RAAS was activated by ECC in both groups. Plasma renin activity (PRA) and plasma angiotensin II-levels (AII) returned to normal range at 6 hours after ECC in group D which is significantly less than group N where PRA and AII remained elevated at 24 hours after ECC. Plasma aldosterone levels (ALD) did not show any significant difference between the two groups. AII changed proportionately to PRA, whereas ALD did not correlate with PRA or AII in the both groups. These results suggested that in early postoperative period angiotensin II didn't cause peripheral vasoconstriction in group D, and administration of DOP in doses of 5 10 micrograms/kg/min resulting in a low level of AII is safe and useful in view of data that a high AII promotes multifocal myocardial necrosis and renal tubular degeneration. PMID- 1895002 TI - [Permanent cardiac pacing in patients on chronic dialysis]. AB - Four patients on chronic dialysis, who underwent permanent pacemaker implantation, were reviewed. The indication for pacing was sick sinus syndrome in three patients and complete atrioventricular block in one. Physiological pacing modes were chosen in all patients (DDD in three and AAI in one). Sensing and pacing properties in these patients studied at implantation and at follow-up (22 41 months after implantation) were similar as those in non-dialysis patients. However, the study of these properties during hemodialysis showed a significant elevation of atrial pacing threshold associated with marked decrease of serum potassium concentration in two patients. We conclude that dialysis patients with significant bradyarrhythmia should be considered for pacemaker implantation in the same manner as non-dialysis patients. However, special attention should be payed on the elevation of pacing threshold during hemodialysis. PMID- 1895003 TI - [Collins blood diluting reperfusion--an effective measure of controlled reperfusion for the heart hypothermically preserved for 24 hours in modified Collins solution]. AB - Controlled reperfusion is assumed to provide an appropriate environment surrounding the ischemic cardiac tissue at the initial reperfusion phase. Hence, this procedure might play a key role in resuscitating the long term preserved hearts. This study was designed to assess the efficacy of the newly devised reperfusion method; namely Collins Blood Diluting Reperfusion (CBDR), for those hearts subjected to 24-hours cold (4 degrees C) storage in modified Collins (MC) solution. Coronary reperfusion is commenced with the MC solution, and the oxygenated blood is successively added to dilute this perfusate with gradual rewarming under controlled perfusion pressure. Initial reperfusate, therefore, is supposed to be a blood cardioplegia with low Ca2+ and high Mg2+ content. During this procedure, any difference in the ionic composition between the storage solution and the reperfusate is completely abolished and myocardium is free from hastiness of temperature elevation. Using an isolated isovolum contracting heart prepared with an ex vivo apparatus incorporating a support dog, each heart was reperfused by unmodified blood (Group I: n = 7) or CBDR method (Group II: n = 10) under equally controlled low perfusion pressure. There was no difference in the myocardial creatine phosphate level between the 2 groups. However, the adenosine triphosphate content, which had been depleted to 30% of the preischemic level during the 24-hour preservation period, was restored to 52.0% after CBDR procedure (p less than 0.01) and consequently to 57.9% of the control at 60 minutes after reperfusion. Group I showed a significantly lower repletion effect at this phase (41.2% control; p less than 0.05 versus group II).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1895004 TI - Learning disabilities and attention deficit-hyperactivity disorder: an interactional perspective. PMID- 1895005 TI - The Regular Education Initiative: a deja vu remembered with sadness and concern. PMID- 1895006 TI - Students with learning disabilities and hearing impairment: issues for the secondary and postsecondary teacher. AB - Although the number of students with both learning disability and hearing impairment (LDHI) currently enrolled in secondary and postsecondary programs has not been precisely determined, it is clear that these students are currently receiving inadequate assessment and support in many institutions. The best route for serving these students would seem to be collaborative efforts between deaf educators and learning disabilities specialists, yet serious gaps exist between these two professions in regard to interpretation of laws governing special services, training of professionals, and locations of educational programs. The difficulties of developing collaborative work have been compounded by controversies within each field and the heterogeneity of the populations served by both disciplines. Those interested in creating good LDHI assessments should begin by considering the qualifications needed by those conducting evaluation procedures. The inadequacies of current formal assessment devices for this population need to be recognized; informal procedures, such as teacher observation and curriculum-based assessments, are still some of the best tools available for identification and educational planning. PMID- 1895007 TI - Correlates of postsecondary employment outcomes for young adults with learning disabilities. AB - The purpose of this study is twofold: (a) to examine the efficiency of a set of selected variables for predicting postsecondary employment success for young adults classified as learning disabled in high school and (b) to provide a portrayal of employment adjustment in the first years after exiting high school. Data on both employment stability and job status were gathered through telephone interviews. Of the 284 students with learning disabilities who exited the four participating high schools between 1986 and 1989, contact was made with 175 (62%). This sample was composed of 75% males, who ranged in age from 18 to 23 years. Statistical tests reveal that students (a) with high math ability, (b) who were employed during high school, and (c) whose parents actively participated in their education were more likely to experience employment success after high school. Overall, 86% of the sample was employed either full- or part-time, with the majority in entry-level, unskilled jobs. In terms of postsecondary education, 26% completed at least one semester of college or technical school, though at the time of follow-up only 13% were enrolled in school. PMID- 1895008 TI - Classroom behavior and family climate in students with learning disabilities and hyperactive behavior. AB - The present study aimed to identify subtypes of the learning disabilities (LD) syndrome by examining classroom behavior and family climate among four groups of Israeli students ranging in age from 7 to 10 years: 22 students with LD and hyperactive behavior (HB), 22 nonhyperactive students with LD, 20 nondisabled students with HB, and 20 nondisabled nonhyperactive students. Schaefer's Classroom Behavior Inventory and Moos's Family Environmental Scale were administered to teachers and mothers, respectively. The results revealed that higher distractibility and hostility among both groups with HB differentiated between the two groups with LD. Families of children with HB were reported as less supportive and as emphasizing control less. The academic competence and temperament of the nondisabled students with HB were rated as similar to those of the two groups of students with LD. Both groups with LD were characterized by dependent interpersonal relations and by more conflictual families who fostered more achievement but less personal growth. PMID- 1895009 TI - Goodness of fit in the home: its relationship to school behavior and achievement in children with learning disabilities. AB - This study examined whether a "goodness of fit" theoretical model, applied to families with and without children with learning disabilities, would be valuable in understanding the children's performance in school. A home interview was conducted with 63 families with a child with learning disabilities and 53 families with a comparable child without learning disabilities. The mothers were asked to rate how their own child fit into the family's expectations for children. It was found that, for both groups of families, children who were rated as a "poor fit" in the home demonstrated less positive behavior in the classroom and poorer achievement over the elementary school years. There was some evidence that poor fit in the home was even more negatively related to outcomes for children with learning disabilities. Discussion is centered on the importance of this theoretical model for understanding the importance of the home on successful school function. PMID- 1895010 TI - Comparisons of learning ease and transfer propensity in poor and average readers. AB - Assisted and unassisted performance of 14 average readers (7 boys and 7 girls between 9.67 and 13 years of age) and 14 children with learning disabilities (10 boys and 4 girls between 10.8 and 13 years of age) were compared on a reading comprehension task--stating the main idea in expository paragraphs in which the topic sentence was either first, last, or missing. Children were trained to find the main idea in one- and two-paragraph texts and took pre- and posttests in which they were asked to write the main ideas contained in one-, and six- to eight-paragraph texts. The main ideas contained in these texts either were explicitly stated (topic sentence first or last) or were implicit (topic sentence missing). Children's performance improved from pre- to posttest, although the effect of topic sentence placement was evident at both test times (performance on topic-sentence-first paragraphs was better than on topic-sentence-last paragraphs, which was, in turn, better than performance on topic-sentence-missing paragraphs). Although average achieving children and children with learning disabilities did not differ on static pre- and posttest measures, they did differ in how easily they learned to find the main idea under different topic sentence placement conditions. Children with learning disabilities required significantly more instruction than average readers to reach mastery criterion on nonideal text structures. Implications of the findings are discussed from both assessment and pedagogical perspectives. PMID- 1895011 TI - Promoting strategy generalization through self-instructional training in students with reading disabilities. AB - Twenty Grade 5 and 6 students with reading disabilities, 20 average readers in Grade 3, and 20 average readers in Grades 5 and 6 were taught to use a self questioning strategy for the identification of main ideas. They were randomly assigned to either a standard instruction or a generalization induction condition. In the latter, informed training and self-instructional training techniques were employed to promote generalization of strategy use. Subjects were posttested under both a cued and an uncued condition in their homerooms. Results indicated that the self-instructional training succeeded in facilitating the identification of main ideas among students with reading disabilities and in helping them to maintain their improved performance when they were no longer prompted to use the strategy in a transfer setting. PMID- 1895013 TI - Conversational engagement of children with learning disabilities. AB - This study was designed to characterize the conversational engagement techniques employed by children with and without learning disabilities while in a dyadic interaction. Engagement was defined and measured in terms of the degree to which utterances provided information and evidenced responsiveness to one's conversational partner. Sixty (30 with learning disabilities and 30 nondisabled) 9- to 13-year-old subjects participated. Analyses indicated that the subjects with learning disabilities (LD) could and did employ engagement-related techniques similar in levels of sophistication to those of their nondisabled peers, although they did so less consistently and frequently. Further, the relationship between affective measures and the engagement-related techniques used by the subjects with LD differed markedly from those of the nondisabled subjects. The results are interpreted from a motivational standpoint and suggest that future research should focus on the knowledge and application of engagement related techniques of the children with LD, across settings and conversational partners. PMID- 1895012 TI - The irrelevance of IQ to the definition of learning disabilities: some empirical evidence. AB - The relevance of IQ to the definition of learning disabilities is a much-debated issue. In this article, the effect of not using IQ in the identification of children with reading disabilities is demonstrated. Two classification procedures, differing in their use of IQ, are compared. The first conclusion is that abandoning IQ in classification has a very limited impact on the number of children identified as reading disordered. Our data demonstrate that, if IQ is used, more high IQ children are classified. Another finding pertains to the effect of a restriction of IQ range. The number of children classified as reading disordered is a function of the IQ range. PMID- 1895014 TI - A sporadic case of bulbospinal muscular atrophy of late onset. AB - We describe a 72-year-old male with bulbospinal muscular atrophy (BSMA) who was being treated for diabetes mellitus and congestive heart failure due to an old myocardial infarction. Although BSMA is a rare form of X-linked spinal and bulbar muscular atrophy of late onset, this case is a sporadic case. We emphasize the importance of recognizing a sporadic case of BSMA. PMID- 1895015 TI - Plasma osmolality in an elderly population. AB - Plasma osmolality was calculated for 303 subjects (152 male and 151 female; mean age 70 +/- 11 years) living in the community. The distribution was normal, and it was not influenced by age, sex, smoking, alcohol intake or use of diuretics. The mean and 95% CI from this study were very close to the reference range given in the Geigy Scientific Tables. Higher values of mean plasma osmolality and wider 95% CI found in previous studies of unselected elderly subjects may simply reflect the higher prevalence of diseases in the elderly. PMID- 1895016 TI - Clinical significance of hypouricemia in hospitalized patients. AB - Serum uric acid was measured in 586 normal subjects and 1,220 hospitalized patients. Hypouricemia was noted in 0.34% of the normal subjects and 2.54% of the hospitalized patients. Among hospitalized patients with hypouricemia, 22 were on medication, including allopurinol, anticancer drugs, antibiotics and glucocorticoids. Twenty-one patients had liver disorders and 11 of them had received transfusions. Neoplastic diseases were noted in 14 patients. Thus, hypouricemia was found to be relatively common in hospitalized patients, and seems to be caused mainly by medication, neoplastic diseases, liver disorders and transfusions. PMID- 1895017 TI - Hyponatremia in a hospital population. AB - The frequency, causes, and outcome of hyponatremia (plasma sodium less than 125 mmol/L), and the value of some routine investigations were studied during a six month period in a hospital population. The incidence and prevalence of hyponatremia were 1.5 and 2.6 per 100 patients per day, respectively. A majority of patients (75%) developed hyponatremia in the hospital. The commonest cause of hyponatremia was normovolemic hyponatremia (79 patients). Hypovolemic and hypervolemic hyponatremia were seen in 63 and 21 patients, respectively. Urine osmolality did not differ between the three groups, and was of little diagnostic value. The mortality in the hyponatremic patients was 41.7%. PMID- 1895018 TI - Temporomandibular joint syndrome: diagnostician's dilemma--a review. AB - A succinct presentation of the definition, historical notations, etiology, anatomy, physiology, pathology, clinical picture, differential diagnosis, treatment, and prognosis of the temporomandibular joint (TMJ) syndrome is presented. Accentuation is placed upon both the etiology of this distress, as well as the need for accurate diagnosis assisted by an elimination process via differential diagnosis. Diagnosticians can discern only what is known to them, Thus, the diagnosis of TMJ syndrome escapes the examiner too frequently. Misdiagnosis results because of the bizarre symptom-complex that mimics many diseases. Failure to diagnose can lead to erroneous empirical treatment that is ineffective. Whereas definitive scientific therapy, programmed to the patient's needs, can be a rewarding therapeutic experience. Moreover, misdiagnosis is a valid basis for a legal cause of action against physicians of all genre. PMID- 1895019 TI - A stochastic model for predator-prey systems: basic properties, stability and computer simulation. AB - A simple stochastic description of a model of a predator-prey system is given. The evolution of the system is described by means of Ito's stochastic differential equations (SDEs), which are the natural stochastic generalization of the Lotka-Volterra deterministic differential equations. Since these SDEs do not satisfy the usual conditions for the existence and uniqueness of the solution, we state a theorem of existence; moreover we study the stability of the equilibrium point and perform a computer simulation to study the behaviour of the trajectories of solutions with given initial data and to estimate first and second moments. PMID- 1895020 TI - The dynamical attainability of ESS in evolutionary games. AB - In this paper, the attainability of ESS of the evolutionary game among n players under the frequency-independent selection is studied by means of a mathematical model describing the dynamical development and a concept of stability (strongly determined stability). It is assumed that natural selection and small mutations cause the phenotype to change gradually in the direction of fitness increasing. It is shown that (1) the ESS solution is not always evolutionarily attainable in the evolutionary dynamics, (2) in the game where the interaction between two species is completely competitive, the Nash solution is always attainable, and (3) one of two species may attain the state of minimum fitness as a result of evolution. The attainability of ESS is also examined in two game models on the sex ratio of wasps and aphids in light of our criterion of the attainability of ESS. PMID- 1895021 TI - Patterns in the effects of infectious diseases on population growth. AB - An infectious disease may reduce or even stop the exponential growth of a population. We consider two very simple models for microparasitic and macroparasitic diseases, respectively, and study how the effect depends on a contact parameter kappa. The results are presented as bifurcation diagrams involving several threshold values of kappa. The precise form of the bifurcation diagram depends critically on a second parameter xi, measuring the influence of the disease on the fertility of the hosts. A striking outcome of the analysis is that for certain ranges of parameter values bistable behaviour occurs: either the population grows exponentially or it oscillates periodically with large amplitude. PMID- 1895022 TI - Consensus in panels and committees: conceptual and ethical issues. PMID- 1895023 TI - Committees and consensus: how many heads are better than one? AB - The first section of this paper asks why the notion of consensus has recently come to the fore in the medical humanities, and suggests that the answer is a function of growing technological and professional complexity. The next two sections examine the concept of consensus analytically, citing some of the recent philosophical literature. The fourth section looks at committee deliberations and their desirable outcomes, and questions the degree to which consensus serves those outcomes. In the fifth and last section it is suggested that if I am to subscribe to a consensual outcome responsibly I must be personally committed to it, and that this requires a form of knowledge I call 'fiduciary', in this case knowledge of the competence and trustworthiness of other participants in deliberation whose expertise may have influenced my agreement. PMID- 1895024 TI - Consensus, contracts, and committees. AB - Following a brief account of the puzzle that ethics committees present for the Western Philosophical tradition, I will examine the possibility that social contract theory can contribute to a philosophical account of these committees. Passing through classical as well as contemporary theories, particularly Rawls' recent constructivist approach, I will argue that social contract theory places severe constraints on the authority that may legitimately be granted to ethics committees. This, I conclude, speaks more about the suitability of the theory to this level of analysis than about the ethics committee phenomenon itself. PMID- 1895025 TI - The epistemology and ethics of consensus: uses and misuses of 'ethical' expertise. AB - In this paper I examine the epistemology and ethics of consensus, focusing on the ways in which decision makers use/misuse ethical expertise. The major questions I raise and tentative answers I give are the following: First, are the 'experts' really experts? My tentative answer is that they are bona fide experts who often represent specific interest groups. Second, is the experts' authority merely epistemological or is it also ethical? My tentative answer is that the experts' authority consists not only in their command over specific matters of fact and/or value, but also in their ability to achieve 'consensus' about what is 'true'/'false', or 'right'/'wrong'. Third, should the authority of expertise be limited? My tentative answer is that it should be limited in the area of facts but especially in the area of values. Persons who are ethics 'experts' must be particularly careful to practice an ethics of persuasion rather than an ethics of compulsion. Their role is not to force their group consensus upon decision makers' individual moral perceptions and deliberations; rather it is to help decision makers come to their own conclusions about what they ought to do. PMID- 1895026 TI - Consensus of expertise: the role of consensus of experts in formulating public policy and estimating facts. AB - For years analysts have recognized the error of assuming that experts in medical science are also experts in deciding the clinically correct course for patients. This paper extends the analysis of the use of the consensus of experts to their use in public policy groups such as NIH Consensus Development panels. After arguing that technical experts cannot be expected to be expert on public policy decisions, the author extends the criticism to the use of the consensus of experts in estimating facts to provide a basis for policy decisions. It is argued that to the extent that (a) experts' views regarding a body of facts can be expected to correlate with their values relevant to those facts; and (b) the values of experts differ from the values of lay people, even the estimates of the facts given by the consensus of expert panels can be expected to differ from the estimates lay people would have given had they had the relevant scientific expertise. PMID- 1895027 TI - Possibilities of consensus: toward democratic moral discourse. AB - The concept of consensus is often appealed to in discussions of biomedical ethics and applied ethics, and it plays an important role in many influential ethical theories. Consensus is an especially influential notion among theorists who reject ethical realism and who frame ethics as a practice of discourse rather than a body of objective knowledge. It is also a practically important notion when moral decision making is subject to bureaucratic organization and oversight, as is increasingly becoming the case in medicine. Two models of consensus are examined and criticized: pluralistic consensus and overlapping consensus. As an alternative to these models, the paper argues that consensus refers to the dialogic aspects of a broader normative conception of democratic moral agency. When the preconditions for that dialogic democratic practice are met, consensus has a justificatory role in ethics; when they are not, consensus, as distinct from mere agreement, does not emerge and can have no moral authority. PMID- 1895028 TI - The expression of actin mRNA in megakaryocytes demonstrated in paraffin sections, and epoxy resin semi-thin and thin sections by in situ hybridization. AB - Megakaryocytes of dog bone marrow were utilized as target cells for identifying actin mRNA expressing cells on semi-thin and thin sections. After in situ hybridization with radioisotope-labeled probes was performed on paraffin sections, gelatin capsules containing freshly prepared epoxy resin were placed on the sections. The resin was solidified and detached from the slide glass, and semi-thin and thin sections were obtained. The signals showing actin mRNA expression were detected on megakaryocytes in these sections by light and electron microscopy. PMID- 1895029 TI - Scanning and transmission electron microscopic observations of chick primordial germ cells with special reference to the extravasation in their migration course. AB - Chick primordial germ cells (PGCs) in the final course of their migration were observed by scanning (SEM) and transmission (TEM) electron microscopy, with an emphasis on their extravasation. The profile of the PGCs leaving blood vessels were first revealed under SEM. Chick embryos at stages 16 and 17 (about 2.5 days of incubation) were employed for the present study, since the PGCs emerging out of the vessels in teh gonadal area could be observed in high frequency at this developmental period. PGCs in the vessels showed a round profile, possessing many microvilli, while extravasating PGCs were rather oligovillous except the one side of the cell, where long filopodia extended toward the wall of the vessels. These filopodia seem to adhere to the wall of the vessels prior to emerging out. After extravasation, PGCs moved toward adjacent prospective gonadal epithelium and invaded it by amoeboidism. Following the settling down in the epithelium, PGCs showed rugged surface with few microvilli. PMID- 1895031 TI - Antibody-decorated dystrophin molecule of murine skeletal myofiber as seen by freeze-etching electron microscopy. AB - Dystrophin is the protein product of Duchenne muscular dystrophy gene which is defective in this genetic disorder. Here we identified ultrastructurally the dystrophin molecule from the various cytoskeletons at the cytoplasmic surface of murine myofiber plasma membrane by using quick-freeze, deep-etch, rotary-shadow replica of anti-dystrophin antibody-decorated muscle samples. The molecule was really cytoskeleton and incorporated in the meshwork of the plasma membrane associated cytoskeletons. The molecule appeared to connect directly and/or through another cytoskeletal molecule with actin filament. PMID- 1895030 TI - An immunocytochemical analysis of a class-specific antibody response against Trichinella spiralis in humans. AB - The response of different classes of antibodies against antigens of the muscle larvae of Trichinella spiralis was tested using an immunocytochemical approach. Ultrathin sections of resin-embedded larvae were treated with sera from patients with trichinosis, then exposed to a biotinated second antibody and stained with avidin-gold complex. Antibody of the M-class was a major component in the response against a slow-responding group of antigens that included stichocyte granules, the cuticle surface, and the esophagus-occupying substance; a minor component in the response against antigens of the rapid-responding group that included cuticle inner layers, hypodermis, hemolymph, and intestinal gland granules. The response of G-class antibody against the rapid-responding group of antigens was detected in all patients tested, while against the slow-responding group of antigens it was detected in only half of the patients, suggesting that an antibody shift from the M to the G class occurred in some patients. The results, obtained in humans, were similar to those we obtained previously in rats (J. Parasitology, 76,230-239, 1990), suggesting that the rat immune system can serve as an experimental model of human trichinosis. PMID- 1895032 TI - An evaluation of guidelines for the apical enlargement of maxillary premolars. AB - A newly proposed set of experimental guidelines for the final size of apical enlargement was evaluated by instrumenting filling and evaluating a series of extracted maxillary premolars. The guidelines were applied to differing anatomical configurations of this type of tooth, and to teeth in which instrumentation terminated at various distances from the foramen. Comparison was made with the conventional guideline of enlarging to three sizes greater than the first instrument that binds, with instrumentation to 0.5 mm from the foramen. All teeth were vacuum injected with India ink and dried, mechanically enlarged according to the experimental or conventional guidelines, and examined for the presence of apically extruded debris. The teeth were then filled, cleared, and visually inspected for the condition of preparation in the apical portion. For the conventional guideline, preparation was generally judged as poor, and debris was usually forced through the foramen. With the experimental guidelines, adequate preparation was obtained for most canal configurations at 0.5 and 1 mm from the foramen, and at 1 mm the incidence of extruded debris fell sharply. Anatomical conditions possibly contraindicating the experimental guidelines were found and characterized. PMID- 1895033 TI - Tumor necrosis factor identified in periapical tissue exudates of teeth with apical periodontitis. AB - Root canal samples, taken from periapical tissue exudates during routine root canal treatment procedures, were processed for identification of tumor necrosis factor using a mouse anti-human monoclonal antibody and enzyme-linked immunosorbent assay. Detectable levels of tumor necrosis factor were identified in periapical tissue exudates in chronic apical periodontitis. PMID- 1895034 TI - Adhesion of sealer cements to dentin with and without the smear layer. AB - The influence of a smear layer on the adhesion of sealer cements to dentin was assessed in recently extracted human anterior teeth. A total of 120 samples was tested, 40 per sealer; 20 each with and without the smear layer. The teeth were split longitudinally, and the internal surfaces were ground flat. One-half of each tooth was left with the smear layer intact, while the other half had the smear removed by washing for 3 min with 17% EDTA followed by 5.25% NaOCl. Evidence of the ability to remove the smear layer was verified by scanning electron microscopy. Using a specially designed jig, the sealer was placed into a 4-mm wide x 4-mm deep well which was then set onto the tooth at a 90-degree angle and allowed to set for 7 days in 100% humidity at 37 degrees C. This set-up was then placed into a mounting jig which was designed for the Instron Universal Testing Machine so that only a tensile load was applied without shearing or applying preloading forces. The set-up was subjected to a tensile load at a crosshead speed of 1 mm per min. The results show significant differences (p less than 0.001) among AH26, Sultan, and Sealapex, with AH26 being the strongest and Sealapex being the weakest. The only significant difference with regard to the presence or absence of the smear layer was found with AH26, which had a stronger bond when the smear layer was removed. PMID- 1895035 TI - Modeling bacterial damage to pulpal cells in vitro. AB - There is increasing evidence that access to patent dentinal tubules by bacteria and their products rather than trauma from restorative materials is responsible for subsequent pulpitides. The purpose of this study was to compare the relative cytotoxicity of centrifugal fractions of two bacteria, Fusobacterium nucleatum and Treponema denticola, on L929 cells in monolayer cultures and in the "in vitro pulp chamber." Neutrophilic chemotaxis assays and Limmulus assays were performed to verify biological activity of the various fractions of these bacteria. It was found that T. denticola inhibits new protein synthesis in cultured cells to a much greater extent than F. nucleatum, but that only F. nucleatum fractions are chemoattractive for human neutrophils in the absence of serum. While the chemical nature and molecular weights of the "toxic" materials were not determined, it appeared that eukaryotic protein synthesis inhibition caused by the T. denticola pellet fraction in the in vitro pulp chamber was at least 1000 times less than that caused by the same concentrations in monolayer cultures. PMID- 1895037 TI - Treatment results of apical surgery in premolar and molar teeth. AB - The purpose of this investigation was to study long-term treatment results following apical surgery in premolars and molars. These results were assessed by reexamination of 136 roots on which apical surgery was performed. The observation period varied from 6 months to 8 yr. According to radiographic and clinical criteria, the treatment results were considered successful in 44.1% of the roots, doubtful in 22.8%, and unsuccessful in 33.1%. Clinical signs and symptoms were associated with 33.1% of the roots, occurring significantly more in roots demonstrating radiographically unsatisfactory healing. The results are discussed with reference to other studies on apical surgery in posterior and anterior teeth. However, methodological differences do not permit the drawing of direct comparisons to those studies. PMID- 1895036 TI - Immune cells in periapical granuloma: morphological and immunohistochemical characterization. AB - Samples of periapical granulomas obtained from 12 patients were examined using light and electron microscopes and monoclonal antibodies. Monocytes/macrophages, lymphocytes, and plasma cells were nearly always the most abundant cell populations. Ultrastructural analysis showed close contacts between macrophages and cells of the lymphoid lineage, with the lymphoid cells frequently demonstrating blastic features. Immunohistochemical staining with the anti interleukin 2 receptor antibody showed that the concentration of labeled cells was quite low. The vast majority were lymphocytes, though some mast cells were also labeled. Mast cells were chiefly located in perivascular areas and interleukin 2 receptor-positive mast cells were frequently associated with lymphoid cells. mast cells could be part of a negative feedback mechanism in the immune response. By releasing histamine, they would block the immune response and by absorbing interleukin 2 they would remove it as an immune system stimulant. PMID- 1895038 TI - Radiographic pulpal calcifications: normal or abnormal--a paradox. AB - A survey was sent to all 525 (domestic) Diplomates of the American Board of Endodontics. It inquired as to the interpretation of the findings of radiographic pulpal calcifications (RPC) and how it might impact on treatment. The response to the question of pathological significance of RPC was divided equally between those who felt it was a sign of pathosis and those who did not. The remaining seven questions were overwhelmingly agreed upon: RPC are important findings included in differential diagnosis; nonsurgical root canal treatment was routinely attempted regardless of the extent of RPC; patients were informed prior to treatment of potential obstacles; and as a rule diplomates devote no more than 10% of their practice to surgical endodontics. PMID- 1895039 TI - Thermally induced pulpalgia in endodontically treated teeth. AB - Two cases of thermally induced pulpalgia in teeth previously endodontically treated are presented. Reproduction of the patient's chief complaint was the key to identifying the teeth involved. In both cases, the pulpalgia was stimulated by heat. After locating and treating an unfilled canal, the teeth have remained asymptomatic. Possible explanations for this occurrence are discussed. PMID- 1895040 TI - Evaluation of size variation between endodontic finger spreaders and accessory gutta-percha cones. AB - The diameter of nine sizes of three brands of endodontic spreaders was measured at D1 and D16 and compared with corresponding sizes of six brands of accessory gutta-percha cones. Two evaluators independently measured 20 randomly selected samples of each size of finger spreader and accessory gutta-percha cone. A standardized method of measurement was used for all samples and the interrater reliability was found to be extremely high using this methodology. Results indicated that very few of the diameters corresponded when like sizes of finger spreaders and accessory gutta-percha cones were compared. We concluded that there is a need for standardization by the manufacturer of finger spreaders so that accessory gutta-percha cones will fit into the space created by corresponding sized finger spreaders. PMID- 1895042 TI - Non-invasive evaluation of long-term cardiac effects of captopril in systemic sclerosis. AB - Impairment of left ventricular (LV) function has previously been reported in patients with systemic sclerosis (SScl). An intermittent vasospastic process in the myocardium may contribute to the development of myocardial dysfunction. Vasodilators may therefore be potentially useful in the treatment of cardiac dysfunction in patients with SScl. This study was designed to evaluate the long term effects of captopril on the myocardial function of patients with SScl. Twenty-two patients with SScl (15 patients with diffuse scleroderma and 7 patients with CREST syndrome, i.e. calcinosis. Raynaud's phenomenon, oesophageal hypomotility, sclerodactyly, telangiectasia) were investigated by means of Doppler and echophonocardiography before and after treatment with captopril (1.3 mg kg-1 body weight d-1) for 11-15 months. There were no significant differences in heart rate, systolic and diastolic blood pressure, end-systolic blood pressure, total peripheral resistance or LV diameters before or after treatment. However, captopril treatment exerted significant effects on LV function: the pre ejection period (PEP) and the ratio of pre-ejection period to LV ejection time decreased significantly (P less than 0.05). Mitral E-point septal separation decreased significantly (P less than 0.01), even after adjustment for LV end diastolic diameter (P less than 0.01). The ejection fraction increased significantly (P less than 0.05), and the isovolumic relaxation time decreased (P less than 0.01). The left atrial emptying index increased (P less than 0.01). The Doppler peak late to early ventricular filling velocity decreased (P less than 0.05), and the isovolumic index was also reduced (P less than 0.05). We conclude that both systolic and diastolic LV function indices improved in patients with SScl after captopril treatment for a mean period of 1 year. The effects of captopril might be due to vasodilation of the myocardial vessels and/or a direct effect on the renin-angiotensin system of the heart. PMID- 1895041 TI - Visceral fat accumulation: the missing link between psychosocial factors and cardiovascular disease? AB - Neuroendocrine responses to psychosocial pressures have been well characterized. The defence reaction is followed by increased activity of the sympathetic nervous system. Essential hypertension might be induced by such mechanisms. The defeat reaction is characterized by increased activity along the corticotropin releasing factor-adrenocorticotropin hormone-cortisol axis, resulting in the inhibition of gonadotropin secretion. Such endocrine disturbances are followed by metabolic aberrations, and probably also by the accumulation of visceral fat. Subjects with abdominal fat accumulation (high waist/hip circumference ratio, WHR) have recently been found to exhibit a number of psychosocial handicaps, together with endocrine aberrations characteristic of the defence and, in particular, the defeat reaction, as well as the associated circulatory and metabolic aberrations. Such abnormalities, including the WHR itself, are established risk factors for cardiovascular disease and diabetes. It is postulated that increased WHR is a symptom of chronic hypothalamic arousal as a result of a defeat reaction to psychosocial pressures. This might lead to the development of disease via circulatory and metabolic derangements. PMID- 1895043 TI - Hand-free stethoscope--method and instrument for more reliable blood pressure measurements. AB - Measurement of blood pressure is subject to two sources of variation: biological and measurement variation. It is important to bear in mind that the ability to interpret the Korotkoff sounds correctly determines the levels of both systolic and diastolic blood pressure. To improve the ability to distinguish between the Korotkoff phases, the handfree stethoscope and the hand-free method were developed. The improved stethoscope head was fixed under the edge of the cuff, thus reducing the noise generated from physiological tremor and other movements. This resulted in more distinct Korotkoff sounds. Furthermore, the new method reduced the spreading of blood pressure values. In 107 patients the average systolic blood pressure recording was 3.1 mmHg higher and the average diastolic blood pressure was 3.5 mmHg lower. We conclude that the new stethoscope and technique provide a means of significantly improving the indirect measurement of blood pressure. PMID- 1895044 TI - Antihypertensive efficacy and tolerability of enalapril and slow-release verapamil in essential hypertension: a double-blind, cross-over study. AB - The antihypertensive efficacy and tolerability of enalapril (E) and slow-release verapamil (V) were compared in a 2-month double-blind cross-over study in 22 patients with mild to moderate essential hypertension. After 1 month, significantly lower systolic (P less than 0.01) and diastolic (P less than 0.02) blood pressures (BP) were achieved with E, 20 mg d-1, compared with V, 240 mg d 1. After 2 months of treatment, BP reductions were similar after E, 40 mg d-1, and V, 240 mg twice a day. The fall in supine mean BP after 2 months of treatment with V was significantly greater in patients aged greater than or equal to 50 years of age (P = 0.02) (median 18 mmHg) than in patients aged less than 50 years (10 mmHg). E showed similar effectiveness in both age groups. Statistical group analysis of a quality-of-life questionnaire showed no significant differences between the active drugs and the placebo. It is concluded that E and V are equally effective as antihypertensive agents, and that both drugs are well tolerated. PMID- 1895045 TI - Long-term prognosis after early intervention with metoprolol in suspected acute myocardial infarction: experiences from the MIAMI Trial. The MIAMI Trial Research Group. AB - A total of 5778 patients with suspected acute myocardial infarction were randomized to early intravenous metoprolol followed by oral treatment for 15 d, or to placebo. Thereafter, the two groups were treated similarly. During a 1-year follow-up period the mortality in patients who were randomized to early metoprolol was 10.6% compared to 10.7% for placebo (P greater than 0.2). Among patients with a higher risk of death, the tendency towards a reduced mortality in the metoprolol group that was observed after 15 d remained similar after 1 year. It is concluded that early intervention with metoprolol in suspected acute myocardial infarction did not improve the long-term prognosis compared to placebo treatment. PMID- 1895046 TI - Sleep difficulties, pain and other correlates. AB - A multiple regression analysis was used with variables relevant to sleeping problems from a large community health survey in South Australia. The variables that were found to be most strongly correlated with sleep problems were, in order of importance, pain, anxiety, age, somatic health and annual household income, all of which accounted for 22% of the variance. Weight problems, depression and sex of the respondent were not so important in this analysis. Arthritis, which often increases with age, appeared to be most strongly associated with pain, explaining in part why sleeping problems increase with age. Anxiety, pain and poor somatic health were most strongly associated with lying awake at night or sleeping badly, and anxiety and pain were most strongly correlated with taking longer to get to sleep. Poor somatic health and anxiety were most strongly associated with waking early, and age and pain were the most important variables in taking tablets to aid sleep. PMID- 1895047 TI - Patients admitted to the emergency room with symptoms indicative of acute myocardial infarction. AB - All 7157 patients (55% men) admitted to the emergency room with chest pain or other symptoms indicative of acute myocardial infarction during a period of 21 months were registered consecutively. Chest pain was reported by 93% of the patients. On the basis of history, clinical examination, and electrocardiogram in the emergency room, all patients were prospectively classified in one of four categories: (i) obvious infarction (4% of all patients); (ii) strongly suspected infarction (20%); (iii) vague suspicion of infarction (35%); and (iv) no suspected infarction (41%). In patients with no suspected infarction (n = 2910), musculoskeletal (26%), obscure (21%) and psychogenic origins (16%) of the symptoms occurred most frequently. We conclude that few of the patients had an obvious infarction on admission, and that a musculoskeletal origin of the symptoms occurred most frequently in patients with no suspected infarction. PMID- 1895048 TI - Colonic epithelial dysplasia or carcinoma in a regional group of patients with ulcerative colitis of more than 15 years duration. AB - Colonoscopic screening for neoplasia was performed in a regional group of ulcerative colitis patients with a disease duration of greater than or equal to 15 years. A total of 121 patients, aged less than 80 years, were invited to participate, of whom 100 (83%) accepted colonoscopy, including biopsies in 15 standard locations of the entire colon, plus additional biopsies from all visible lesions. Unequivocal dysplasia was found in one patient with extensive colitis and a disease duration of 31 years. A polyp with highly differentiated adenocarcinoma was found in the sigmoid colon of a patient with intermittent rectum involvement, 37 years after the ulcerative colitis diagnosis had been made. Biopsy specimens from the remaining 98 patients showed no signs of dysplasia or cancer. Thus the frequency of pre-malignant or malignant changes is very low compared with the results of similar studies, and the rationale for general colonoscopic surveillance programmes for such patients is open to question. PMID- 1895049 TI - Screening for haemochromatosis: prevalence among Danish blood donors. AB - Hereditary haemochromatosis is an autosomal recessive disease that is genetically expressed by excessive accumulation of iron in the tissues, resulting in cirrhosis, diabetes mellitus, cardiomyopathy and hypogonadism. As the disease may be diagnosed before the appearance of symptoms, and prevented by repeated phlebotomies, there are strong implications for adoption of a screening procedure. Determinations of transferrin saturation (TS) and serum ferritin concentration (SF) were used to screen 4302 blood donors, who were selected for follow-up studies if they fulfilled any of the following three criteria: (i) TS greater than or equal to 0.7; (ii) TS greater than or equal to 0.5 together with SF greater than or equal to 150 micrograms l-1; (iii) SF greater than or equal to 300 micrograms l-1. A total of 58 subjects who fulfilled at least one of these criteria were reinvestigated, after which 18 individuals still fulfilled at least one criterion. Fifteen subjects having SF greater than or equal to 300 micrograms l-1 were offered liver biopsy and thirteen of these accepted. In one individual, no stainable iron was detected, and two subjects did not fulfil the previously established diagnostic criteria for the diagnosis of hereditary haemochromatosis. Ten subjects who had a high TS and liver iron grade 2-4 according to Bassett were classified accordingly as homozygotes. On the basis of these results, the prevalence of haemochromatosis in Denmark was estimated to be 0.0037-0.0046. PMID- 1895050 TI - Clinical symptoms in young adults with atypical chest pain attending the emergency department. AB - Clinical symptoms were studied in 69 consecutive patients below the age of 40 years who were attending the emergency unit because of unexplained chest pain. In a structured interview a few weeks after the emergency visit, only one-third of the patients reported that they believed in the doctor's diagnosis; they believed in a psychological or cardiac origin of the pain more often than the doctors. The chest pain was most often described as oppressive and/or stabbing. In 95% of cases it was central or left-sided. Associated symptoms were commonly reported, breathlessness being most commonly reported by two-thirds of the patients, followed by dizziness, palpitation and numbness/tingling. Mental symptoms such as tiredness, anxiety and tension were frequently reported. On the basis of the background literature the aetiology is discussed. We conclude that immediate symptom analysis, including psychosomatic symptoms, particularly breathing problems, is of central importance. PMID- 1895051 TI - Intravenous prostacyclin in thrombotic thrombocytopenic purpura: case report and review of the literature. AB - The use of prostacyclin infusion in thrombotic thrombocytopenic purpura is consistent with the hypothesis that patients may lack a plasma factor stimulating prostacyclin production. However, prostacyclin therapy, alone or in combination with aspirin, dipyridamole, steroid and plasmapheresis, failed in many cases. We here describe the case of a patient who responded dramatically to a combination of prostacyclin and plasma infusions, after conventional therapy had failed (plasmapheresis, fresh frozen plasma infusions). Prostacyclin was infused intravenously initially for 120 h from 4 to 9 ng kg min-1 and then continuously for 48 h at 9 ng kg min-1. Despite the scarcity of case reports in the literature, we conclude that the failure of prostacyclin in thrombotic thrombocytopenic purpura appears to be related to insufficient doses and/or duration of therapy. PMID- 1895052 TI - Paraproteinaemia in relatives of patients with primary acquired agammaglobulinaemia. AB - Two instances of the unusual familial association of severe primary acquired hypogammaglobulinaemia and paraproteinaemia are described, and previous reports of familial immunoglobulin dyscrasias are discussed. Our observations lend further support to the possible existence of a genetic predisposition to these disorders. PMID- 1895053 TI - Isolated cryptococcosis of the adrenal gland. AB - A case of isolated adrenal cryptococcosis is reported. A patient with a history of diabetes mellitus had symptoms of left flank pain. Roentgenological and sonographic findings of the adrenal gland were indicative of a malignant tumour. Tissue obtained from surgery showed fungal granuloma and a poorly encapsulated cryptococcal organism was identified by special stains. A post-operative serum cryptococcal antigen test was positive, and the patient was successfully treated with surgery and a course of amphotericin B. After a 7-month follow-up period, there is no evidence of recurrence or dissemination. PMID- 1895054 TI - Identification of variable domains of the attachment (G) protein of subgroup A respiratory syncytial viruses. AB - We have previously classified isolates from a respiratory syncytial (RS) virus epidemic into distinct lineages by restriction mapping and nucleotide sequencing of parts of the nucleocapsid protein and small hydrophobic protein genes, which are areas of the genome not considered to be under immunological pressure. This study has now been extended by the determination of the nucleotide sequences of the attachment (G) protein genes of isolates from each subgroup A lineage. Deduced amino acid identities of the G proteins ranged between 80% and 99%, corresponding closely to the previously determined relatedness of the lineages. The amino acid variability was not evenly distributed; in the extracellular part of the protein there was a sharply defined hypervariable domain which was separated from a more extended variable domain by a highly conserved region. Most nucleotide changes in the variable domains were in the first and second positions of the codon triplets. These results suggest that there may be considerable immunological pressure for change in certain areas of the G protein and this may account for the ability of this virus to reinfect individuals repeatedly. The results presented here reflect the pattern of published data comparing prototype strains of the A and B subgroups. PMID- 1895055 TI - Nucleotide sequence of raspberry bushy dwarf virus RNA-2: a bicistronic component of a bipartite genome. AB - Northern blot analysis with cDNA probes to RNA-3 (1 kb) of raspberry bushy dwarf virus (RBDV) revealed extensive sequence homology with RBDV RNA-2 (2.2 kb). Nucleotide sequencing showed that RNA-2 contains two large open reading frames (ORFs), of 1074 (5' ORF) and 822 (3' ORF) bases. The 3' ORF is virtually identical in sequence to RNA-3, which encodes the Mr 30509 (30K) coat protein. The 5' ORF encodes an Mr 38860 (39K) protein which slightly resembles the 32K protein encoded by RNA-3 of alfalfa mosaic virus (AlMV). RBDV RNA-2 resembles AlMV RNA-3 in being bicistronic and encoding a coat protein at the 3' end. Comparing RNA-1 and RNA-2 of RBDV, only the 18 3'-terminal nucleotides are identical in sequence but the 3'-terminal 71 nucleotides of each RNA species have the potential to form similar stem-loop structures. PMID- 1895056 TI - Evolutionary relationships in the cucumoviruses: nucleotide sequence of tomato aspermy virus RNA 1. AB - RNA 1 of the V strain of tomato aspermy virus (TAV) consists of 3410 nucleotides and contains one open reading frame (ORF) of 2982 nucleotides, resembling RNA 1 of cucumber mosaic virus (CMV) strains Q and Fny (68% and 66% identical, respectively) and of brome mosaic virus (BMV) (41% identical). In comparisons between amino acid sequences, three conserved regions (N-terminal, C-terminal and central) between TAV and each CMV were found. The N- and C-terminal regions were also conserved with BMV, and contained, respectively, consensus motifs for methyltransferases and for nucleic acid helicases. The 5' and 3' non-coding sequences were highly similar to those of TAV RNA 2. When the sequences for the genomic RNAs of the V and C strains of TAV, and of their encoded products, are compared with those reported for CMV strains representing either subgroup I (Fny CMV) or subgroup II (Q-CMV) of CMV, it was found that the different virus-encoded proteins are conserved differently between these three viruses. Also, the divergence between TAV and both CMV subgroups has proceeded at different rates for the different ORFs. On the whole, the divergence between TAV and CMV is of the same order as that found between CMV subgroups I and II, which suggests that TAV, Q-CMV and Fny-CMV could be considered as representing three equivalent subgroups of a taxonomic entity. PMID- 1895057 TI - The phylogeny of RNA-dependent RNA polymerases of positive-strand RNA viruses. AB - Representative amino acid sequences of the RNA-dependent RNA polymerases of all groups of positive-strand RNA viruses were aligned hierarchiacally, starting with the most closely related ones. This resulted in delineation of three large supergroups. Within each of the supergroups, the sequences of segments of approximately 300 amino acid residues originating from the central and/or C terminal portions of the polymerases could be aligned with statistically significant scores. Specific consensus patterns of conserved amino acid residues were derived for each of the supergroups. The composition of the polymerase supergroups was as follows. I. Picorna-, noda-, como-, nepo-, poty-, bymo-, sobemoviruses, and a subset of luteoviruses (beet western yellows virus and potato leafroll virus). II. Carmo-, tombus-, dianthoviruses, another subset of luteoviruses (barley yellow dwarf virus), pestiviruses, hepatitis C virus (HCV), flaviviruses and, unexpectedly, single-stranded RNA bacteriophages. III. Tobamo-, tobra-, hordei-, tricornaviruses, beet yellows virus, alpha-, rubi-, furoviruses, hepatitis E virus (HEV), potex-, carla-, tymoviruses, and apple chlorotic leaf spot virus. An unusual organization was shown for corona- and torovirus polymerases whose N-terminal regions were found to be related to the respective domains of supergroup I, and the C-terminal regions to those of the supergroup III polymerases. The alignments of the three polymerase supergroups were superimposed to produce a comprehensive final alignment encompassing eight distinct conserved motifs. Phylogenetic analysis using three independent methods of three construction confirmed the separation of the positive-strand RNA viral polymerases into three supergroups and revealed some unexpected clusters within the supergroups. These included the grouping of HCV and the pestiviruses with carmoviruses and related plant viruses in super-group II, and the grouping of HEV and rubiviruses with furoviruses in supergroup III. PMID- 1895058 TI - Tomato spotted wilt virus L RNA encodes a putative RNA polymerase. AB - The complete nucleotide sequence of the large (L) genome segment of tomato spotted wilt virus (TSWV) has been determined. The RNA is 8897 nucleotides long and contains complementary 3' and 5' ends, comprising 62 nucleotides at the 5' end and 66 nucleotides at the 3' end. The RNA is of negative polarity, with one large open reading frame (ORF) located on the viral complementary strand. This ORF corresponds to a primary translation product of 2875 amino acids in length, with a predicted Mr of 331,500. Comparison with the polymerase proteins of other negative-strand viruses indicates that this protein most likely represents the viral polymerase. The genetic organization of TSWV L RNA is similar to that of the L RNA segments of Bunyamwera and Hantaan viruses, animal-infecting representatives of the Bunyaviridae. PMID- 1895059 TI - Heterologous encapsidation in mixed infections among four isolates of barley yellow dwarf virus. AB - We used immunohybridization and ELISA to investigate heterologous encapsidation (transcapsidation and phenotypic mixing) between paired isolates of barley yellow dwarf virus (BYDV) in doubly infected oat plants, Avena sativa L. cv. Clintland 64. Virons in samples extracted from plants doubly infected with two viruses were trapped with an antibody specific to one virus, and the nucleic acids of the trapped virions were identified with a cDNA probe specific to the other. Heterologous encapsidation was found in mixed infections between isolates NY-RPV and NY-MAV-PS1, NY-RPV and P-PAV, NY-RMV and NY-MAV-PS1, P-PAV and NY-MAV-PS1, and NY-RPV and NY-RMV. Heterologous encapsidation between NY-RPV and P-PAV, and between NY-RPV and NY-MAV-PS1, occurred in one direction, while the heterologous encapsidation between P-PAV and NY-MAV-PS1 occurred in both directions. Further analysis by heterologous ELISA and immunohybridization assays with immunoprecipitated samples demonstrated that transcapsidation was the predominant type of heterologous encapsidation in mixed infections of NY-RPV and P-PAV, NY RPV and NY-MAV-PS1, and NY-RMV and NY-MAV-PS1; phenotypic mixing was the predominant type of heterologous encapsidation in mixed infections of P-PAV and NY-MAV-PS1. Phenotypic mixing was also detected in mixed infections of NY-RPV and NY-RMV. These results suggest that among BYDV isolates transcapsidation is more common between distantly related isolates than between more closely related isolates, and phenotypic mixing is more common between more closely related isolates than distantly related isolates. PMID- 1895060 TI - Outer capsid protein heterogeneity of rice dwarf phytoreovirus. AB - The 46K outer capsid protein encoded by RNA segment S8 and the 42K polypeptide, previously thought to be the segment S9-encoded structural protein, were isolated from a rice dwarf phytoreovirus purified preparation, and then analysed by peptide mapping and electroblot-ELISA. Staphylococcus aureus V8 protease peptide mapping patterns of the 42K and 46K proteins were similar. Two monoclonal antibodies (MAbs), obtained after immunization with virus particles dissociated by 0.1% SDS, were each specific for both the 42K and 46K proteins. Furthermore, the MAbs bound common peptide fragments which were generated by digestion of the 42K and 46K proteins with V8 protease or proteinase K. These results strongly suggest that the 42K protein is not a gene product of S9 but a product overlapping with the 46K outer capsid protein. Whether the two proteins are functionally distinct remains to be determined. PMID- 1895061 TI - Effect of recombinant beet necrotic yellow vein virus with different RNA compositions on mechanically inoculated sugarbeets. AB - Beet necrotic yellow vein virus (BNYVV) inocula with different RNA compositions were prepared from infectious transcripts of RNAs 3 and 4 and the Rg 1 isolate, which has a genome consisting only of RNAs 1 and 2. The recombinant viruses were inoculated on 6- to 8-day-old sugarbeet seedlings by 'vortexing'. Inocula containing RNAs 1 and 2 or 1, 2 and 4 produced some growth reduction, but the most dramatic effects, with yield reductions of about 95% in a highly susceptible variety, were seen when RNA 3 was also present in the inoculum. Under these conditions the side roots were brown and brittle and often deteriorated, but 'root beardedness' was not observed. This might be due to the fact that our experiments were done in the absence of Polymyxa betae. Alternatively, the heavy inoculation at a very young age may either have weakened the plants to such an extent that extensive root proliferation was impaired or it may have led to rapid deterioration of the proliferating rootlets, which would therefore be lost prior to or during removal of the tap roots from the soil. In the presence of RNA 3 the virus concentrations in tap roots were markedly increased suggesting that this RNA facilitates the multiplication and/or spread of the virus in root tissues. PMID- 1895062 TI - Molecular cloning, sequencing and expression in Escherichia coli of the odontoglossum ringspot virus coat protein gene. AB - The sequence of the 3'-terminal 1865 nucleotides of the genome of the tobamovirus odontoglossum ringspot virus (ORSV) was determined. This sequence contained two open reading frames (ORFs), 912 and 477 nucleotides long. The 912 nucleotide ORF has been identified as the cell-to-cell transport protein gene. The 477 nucleotide ORF was expressed in Escherichia coli, and the product was detected by antibodies specific for the coat protein of ORSV. The amino acid sequence of protein encoded by this ORF shares 84% similarity with the tobacco mosaic virus (TMV) (vulgare) coat protein. The 3'-terminal untranslated region of ORSV comprises 414 nucleotides, 210 nucleotides more than that of TMV (vulgare) RNA. PMID- 1895063 TI - Analysis of Borna disease virus-specific RNAs in infected cells and tissues. AB - Borna disease virus (BDV) is an infectious agent that causes profound disturbances in motor function and behaviour in a wide range of animal species and possibly humans. The infectious nature of BDV has long been established, but the aetiological agent has not been isolated or classified. Recently, we have reported the isolation of BDV-specific cDNA clones using subtractive libraries constructed from mRNA from infected material. Here we describe studies on one of these cDNA clones, B8, and confirm its specificity by in situ hybridization on sections of BDV-infected brain. The complete nucleotide sequence of BDV-specific clone B8 was determined. Oligonucleotides of positive and negative polarity synthesized from sequences from the 5' and 3' ends, as well as the central part, of clone B8 identified both positive- and negative-strand BDV-specific RNAs in infected rat brain. All B8 sequences used as oligonucleotide probes were found to be contained in the larger positive- and negative-strand RNAs. Thus, the structure of the BDV-specific RNAs appears to be a nested set of multiple, overlapping subgenomic positive- and negative-strand RNA transcripts. PMID- 1895064 TI - Actin-independent maturation of rabies virus in neuronal cultures. AB - This study outlines the effects of a modification of the actin-based cytoskeleton on the maturation of rabies virus in human neuroblastoma cell and primary rat cortical neuron cultures. In a Ca(2+)-depleted or an EGTA-containing medium, disruption of microfilaments did not affect intracellular viral nucleoprotein synthesis, as demonstrated by dual-immunofluorescence microscopy, and caused no change in the extracellular titre of rabies virus. Furthermore, the continuous presence of the anti-calmodulin drugs trifluoperazine (1 to 20 microM) and chlorpromazine (1 to 30 microM), or the L-type Ca2+ channel antagonist nifedepine (1 to 10 microM) or the Ca(2+)-specific ionophore A23187 (0.05 to 1.0 microM), did not modify the extracellular titre of rabies virus significantly over a 48 h period. The inference from these studies is that the maturation of rabies virus is independent of the integrity of the microfilament structures and calmodulin dependent processes of neuronal cells. PMID- 1895065 TI - Nucleotide sequence of the genes encoding the matrix protein of two wild-type measles virus strains. AB - The nucleotide sequences of the matrix protein (M) genes of two wild-type measles virus (MV) isolates (JM and CM) have been determined and shown to differ in 56 positions; 31 of these differences are located in the non-coding region and 25 in the coding region of the gene. Most (80%) of the mutations in the coding region are changes to the third base of a codon. A maximum parsimony analysis of the available M gene nucleotide sequences allowed the construction of a tree with at least three lineages or subtypes. One wild-type strain (JM) was very similar to a subacute sclerosing panencephalitis virus strain (case B); the second wild-type strain, CM, showed nucleotide sequence similarity with MV from a case of measles inclusion body encephalitis. Both wild-type virus sequences are distinct from those so far determined for vaccine strains. PMID- 1895066 TI - Conserved domains of glycoprotein B (gB) of the monkey virus, simian agent 8, identified by comparison with herpesvirus gBs. AB - The herpesvirus simian agent 8 (SA8) gene which corresponds to the herpes simplex virus (HSV) gene encoding glycoprotein B (gB) was localized, cloned and sequenced. Comparison of its deduced amino acid sequence with those of its counterparts in 12 other distinct herpesvirus was used to evaluate their homology and phylogenetic relationship. The results emphasized that SA8 gB is more closely related to those of HSV-1 and -2, and bovine herpesvirus 2 than to the homologous proteins of other herpesviruses. Furthermore, the alignment showed several regions of domains conserved in the closely related sequences, including four conserved in all the herpesvirus gB sequences examined. The conservation of 10 cysteine residues and most of the proline residues, as well as several potential N-glycosylation sites, suggested that the secondary and tertiary structures of these gBs were similar. PMID- 1895067 TI - Amplification of the Moloney murine leukaemia virus genome and its possible role in facilitation of chemical carcinogenesis in normal rat kidney cells. AB - In a previous study we have shown that a single infectious particle of Moloney murine leukaemia virus per cell is sufficient to facilitate chemical carcinogenesis in normal rat kidney cells. When these cells are exposed to the carcinogen after a low number of passages post-infection (p.i.), cell transformation becomes apparent only after many subsequent passages. On the other hand, when exposure is done after a high number of passages p.i., cell transformation can be detected in the treated culture or at the next passage. It is thus evident that whereas the carcinogenic effect is rapid, the viral effect becomes apparent only after a long period of latency. Here we provide evidence that this viral effect requires multiple proviruses and that the long latent period reflects the time needed for a sufficient accumulation of proviruses in some of the cells. This accumulation may result from multiple rounds of superinfection by virions released into the culture medium, although we cannot exclude other mechanisms of provirus amplification. Our data also suggest that this amplification enhances virus production. PMID- 1895068 TI - The relationship between coping style and loneliness in adolescents: can "sad passivity" be adaptive? AB - The authors' purpose in this paper was to examine how the use of the "sad passive" coping style may be related to adolescent self-reported loneliness. Subjects were asked to complete the revised UCLA Loneliness Scale (Russell, Peplau, & Cutrona, 1980) to determine self-reported loneliness and the Coping with Loneliness Questionnaire (CLQ; Rubenstein & Shaver, 1980) in order to examine coping styles. We hypothesized that those adolescents whose coping strategies fell into the category of sad passivity described by Rubenstein and Shaver would indicate greater loneliness than those adolescents whose coping strategies fell into other categories. Results indicated that sad passivity was used by both lonely and nonlonely adolescents, but that nonlonely youngsters resorted to this method only temporarily and in preparation for a more active coping style. Lonely teens, on the other hand, appeared to remain in the sad passive mode to a maladaptive degree. These results were discussed in terms of their importance for theories of adolescent loneliness and for possible intervention strategies. PMID- 1895069 TI - A developmental account of early childhood amnesia. AB - This study was an attempt to demonstrate the utility of a developmental approach to the study of early childhood amnesia. Working from a model of early childhood memory development proposed by Nelson and Ross (1980), I hypothesized that children would show early childhood amnesia and that this could be tested by comparing obtained estimates of memory strength to values predicted by a standard retention function. The data confirm this hypothesis for 6- and 10-year-old children, and suggest that the early childhood amnesia period extends from birth to a point between the third and fourth birthdays. The data also support a prediction, derived from the aforementioned model, that children would report a disproportionate number of general memories from the amnesia period. Thus, the developmental model provides a useful vehicle for examining early childhood amnesia and helps to frame further questions such as why some specific memories from this period are retained even though most are lost. PMID- 1895070 TI - Posttraumatic recovery of traumatized newborns: effects on neuromotor and cognitive development during their first 6 months. AB - Recovery after perinatal cerebral traumatism was studied in a group of 20 traumatized infants. The effects on the sequence of development during the next 6 months were observed for both motor and cognitive development and were compared with a control group of 20 normal babies. Results showed a significant delay for the abnormal group and a different recovery pattern between these two aspects of development. Motor development reached a normal level at 4 months, whereas cognitive development was still impaired at 6 months. These results were discussed in terms of possibly longer effects of perinatal traumatism on higher cortical functions than on motor functions. PMID- 1895071 TI - Siblings in dyads: relationships among perceptions and behavior. AB - The ways in which middle-childhood siblings perceive themselves as similar or different was assessed with a sample of 40 pairs of 9- to 11-year-old (younger) and 12- to 14-year-old (older) siblings. Each child was interviewed and completed a card sort procedure and a measure of self-competence. Sibling pairs participated in three behavioral tasks coded for cooperation and conflict. Self ratings, self-perceptions, and sibling behavior were analyzed for their association with the perceived similarity construct. Siblings perceived themselves as being more like one another than did their mothers. Forty-one percent of the variance in their perceived similarity was accounted for by paired self-cooperation ratings, social competence, and behavioral task scores. PMID- 1895072 TI - Father-child relationships from the preschool years through mid-adolescence. AB - In this study, we examined variations in fathering and father-child relationships from the children's preschool years through mid-adolescence. One hundred seventy seven fathers with first-born children ages 4, 8, 12, and 16 years responded to five sets of questionnaires tapping four domains of childrearing: practices, attitudes, parental role involvement, and role satisfaction. A multivariate analysis of variance identified significant variability among the four age groups in fathers' use of acceptance in childrearing practices, role involvement (frequency and task sharing), satisfaction with paternal role performance, and attitudes about the modifiability of child behavior. The results contribute new information about the nature of fathering throughout the childhood years and adolescence and provide additional support for the view of parenting as dynamic and responsive to the developmental level and gender-related characteristics of the child. PMID- 1895073 TI - Cerebral lateralization of bilingual functions after handedness switch in childhood. AB - Chinese-English bilingual undergraduates who had been forced to switch their preferred hand from the left to the right during childhood were identified. In hemifield perception of Chinese and English words, ordinary left-handers and handedness-switch subjects showed a less strong left-hemisphere advantage when compared with right-handers. The latter showed a significant superiority in identifying words presented in the right visual field. Handedness switch during early childhood did not seem to affect lateralization of language functions, although other motor functions may be affected. PMID- 1895074 TI - Effect of body size on the vector competence of field and laboratory populations of Aedes triseriatus for La Crosse virus. AB - Aedes triseriatus females collected as pupae from 2 tireyards and one woodlot were tested for susceptibility to La Crosse virus infection and ability to transmit the virus to suckling mice. Rates of disseminated infection and oral transmission were inversely correlated with mean body size. The smallest population developed disseminated infections and transmitted virus at significantly higher rates than the 2 larger populations. Adults derived from F1 eggs of the largest and smallest populations showed no significant differences in rates of disseminated infection and transmission, suggesting that the differences between the field populations were primarily caused by larval rearing conditions. When pupae of 2 strains of Ae. triseriatus were arranged into discrete size groups and tested for susceptibility to virus, an inverse relationship was observed between rate of disseminated infections and mean pupal wet weight. In contrast, Ae. hendersoni exhibited low transmission rates (7-10%) regardless of body size. PMID- 1895075 TI - Field trials with Vectolex (Bacillus sphaericus) and Vectobac (Bacillus thuringiensis (H-14)) against Anopheles gambiae and Culex quinquefasciatus breeding in Zaire. AB - Under field conditions in Kinshasa, Zaire, an aqueous suspension of Bacillus thuringiensis (H-14), Vectobac (12-AS), lost most of its larvicidal activity at all concentrations after 48 h against Culex quinquefasciatus breeding in polluted gutter water and Anopheles gambiae breeding in clear water irrigation ponds. However, good control of Cx. quinquefasciatus was obtained using a granular formulation of B. sphaericus, Vectolex-G (ABG-6185), at concentrations of 10-30 kg/ha. High concentrations of Vectolex-G gave excellent control of An. gambiae breeding in irrigation ponds. The Vectobac-G was less active against An. gambiae than Vectolex-G, in spite of good dispersion of Vectobac-G particles. PMID- 1895077 TI - Compatibility of Bacillus thuringiensis var. Israelensis and Bacillus sphaericus with the fungal pathogen Lagenidium giganteum (Oomycetes: Lagenidiales). AB - Larvae of Culex quinquefasciatus were exposed to infection by Lagenidium giganteum and various concentrations of B.t.i. or B. sphaericus. The resulting larval mortalities, percentages of infected dead larvae and percentages of larval body regions containing the fungus were compared. Overall, the effectiveness of Lagenidum giganteum against the larvae was not significantly affected by the presence of B.t.i. or B. sphaericus, and the fungal and bacterial agents were compatible. In experiments using 3-day-old larvae, the extent of growth of the fungus in the infected larvae and the percentage of the larvae infected were related to the concentration of B.t.i. in the range of 0.057-0.456 ITU/ml tested but were not related to the concentration of B. sphaericus in the range of 0.6 4.8 x 10(4) spores/ml. With larvae of various ages treated with a low concentration of B.t.i. (0.114 ITU/ml), exposure to the fungus increased the mortality rate in early but not late instars. After single and multiple applications of B.t.i. and B. sphaericus in the presence of the fungus, followed by drying and reflooding, the fungus persisted and reinfected larvae while the B. sphaericus persisted but the B.t.i. did not. PMID- 1895076 TI - Age structure and abundance levels in the entomological evaluation of an insecticide used in the control of Anopheles albimanus in southern Mexico. AB - Applications of bendiocarb produced a high insecticidal residual effect lasting up to 3 months on the most common indoor house surfaces. No significant decreases in mosquito man-biting rate levels were observed between treated and untreated villages. It was shown that almost equal proportions of intra- and peridomicillary mosquitoes came into contact with the insecticide, indicating that mosquitoes commonly enter houses, rest on treated surfaces and return to bite both indoors and outdoors. Although the insecticide was found to have a significant effect on the percentage parity (interpreted as abundance of older individuals) of intra- and peridomicillary Anopheles albimanus mosquitoes, parity recovered and continued a normal cyclic pattern that appeared to be dependent on relative abundance. The proximity of a treated village to an untreated village (1.2 km) can affect the age structure of mosquito populations through shared common resting and breeding sites. PMID- 1895078 TI - Impact of the entomophilic digenean Plagiorchis noblei (Trematoda: Plagiorchiidae) on the survival of Aedes provocans under field conditions. AB - Under field conditions, exposure of Aedes provocans to Plagiorchis noblei cercariae reduced the number of pupae produced to about one-third of control values. Larvae bearing more than 2 metacercariae rarely survived, and pupal mortality was almost 3 times higher among exposed individuals than controls. Adult females exposed to cercariae as pre-imagos experienced a 32% reduction in longevity. The life span of males was not affected. The potential of entomophilic digeneans as biological agents in the control of mosquitoes is discussed. PMID- 1895079 TI - Efficacy of various ground-applied cold aerosol adulticides against Anopheles quadrimaculatus. AB - Ground-applied ULV, cold aerosol insecticides were tested against adult female Anopheles quadrimaculatus. Treatments included high (H) and low (L) rates of Permanone (permethrin), bioresmethrin and esbiothrin. Malathion was applied as a standard. Mortality at 24-h posttreatment was highest with Bioresmethrin H at 15 m. Permanone H exhibited good control out to 60 m (88.9%), but dropped to an unacceptable level (65.5%) at 90 m. The low rates of all compounds produced unsatisfactory results at 24-h posttreatment. Recovery from knockdown occurred in all treatments with the exception of malathion. PMID- 1895080 TI - Activity of lambda-cyhalothrin applied as an ultralow volume ground treatment against Anopheles quadrimaculatus adults. AB - Lambda-cyhalothrin was evaluated as an ultralow volume ground adulticide treatment at rates of 0.25, 0.5 and 1.0 g/ha. Resmethrin, a standard adulticide, was applied at a rate of 1.96 g/ha. All treatments provided greater than or equal to 95% control up to 50 m from the spray route. The highest rate of lambda cyhalothrin and the resmethrin standard provided greater than or equal to 95% control up to 200 m, which is twice the distance normally assessed in this type of testing. Control was reduced at 200 m for the 0.25 and 0.5 g/ha rates of lambda-cyhalothrin, which provided 73 and 88% mortality, respectively. Lambda cyhalothrin appears to have the insecticidal activity required for operational mosquito control. PMID- 1895081 TI - Estimation of survival and gonotrophic cycle length of Culicoides variipennis (Diptera: Ceratopogonidae) in California. AB - The use of a time series analysis to estimate the survival rate and gonotrophic cycle length of Culicoides variipennis at 2 California sites is described. Collections were made daily for 28 days in Yolo County (northern California) and for 25 days in Riverside County (southern California) in July and August of 1989, respectively, using CO2-baited suction traps. The time series analysis of these collections yielded a gonotrophic cycle length estimate of 3 days. Stage-specific and daily survivorship estimates 0.242 and 0.623, respectively, were determined for the northern California site. The time series method was found unsuitable for estimating the gonotrophic cycle length or daily survivorship at the southern California site. PMID- 1895082 TI - Comparison of floating and sinking encapsulated formulations of the fungus Lagenidium giganteum (Oomycetes: Lagenidiales) for control of Anopheles larvae. AB - Floating calcium alginate capsules containing Lagenidium giganteum and 1% ground cork gave higher levels of control of Anopheles quadrimaculatus larvae in a 100 cm column of water than sinking capsules containing no cork. There was no significant difference between the cork capsules and the sinking capsules in the infection of larvae by the encapsulated fungus after storage (15 degrees C) for 57 days, although infectivity declined during that time from an initial infection rate of 100% to 35% and 40% for the cork and sinking capsules, respectively. Floating capsules containing glass bubbles were less effective than the cork capsules in the 100-cm column of water and had a shorter storage life than either sinking capsules or cork capsules. PMID- 1895083 TI - Resistance in Anopheles culicifacies sibling species B and C to malathion in Andhra Pradesh and Gujarat States, India. AB - Studies conducted in Warangal, Khammam and Mahabubnagar districts in Andhra Pradesh and Surat district in Gujarat have revealed that Anopheles culicifacies sensu lato (s.l.) populations were resistant to malathion. In the absence of indoor spraying of malathion in public health programs in the 3 districts of Andhra Pradesh, resistance is attributed to the extensive use of pesticides in agriculture. Species B and C were sympatric in all areas surveyed, and both the species were resistant to malathion. In most of the surveys carried out in Mahabubnagar, Khammam and Warangal, levels of resistance were higher in species C than in B. In Mahabubnagar district an increase in resistance from 5.5 to 64% was observed from 1985 to 1987 in An. culicifacies s.l. The proportion of species C was low in the initial 2 surveys, and in the later surveys the proportion was almost equal to that of species B; the resistance level was also significantly higher than in species B. In Surat district, where resistance ranged from 74 to 93%, the level of resistance in the 2 species was almost the same. PMID- 1895084 TI - Perspectives on management of pestiferous Chironomidae (Diptera), an emerging global problem. AB - In recent years, adult Chironomidae emerging from some urban natural or man-made habitats have increasingly posed a variety of nuisance and economic problems, and in some situations medical problems to humans in different parts of the world. Although there are an estimated 4,000 or more species of chironomid midges worldwide, less than 100 species have been reported to be pestiferous. Among midge control methods, numerous laboratory and field studies have been conducted on the use of organochlorines, organophosphates (OPs), pyrethroids and insect growth regulators (IGRs). Field use of OP insecticides such as chlorpyrifos, temephos and others in the USA and Japan has generally resulted in larval control for 2-5 wk or longer with application rates below 0.56 kg AI/ha (USA) and less than 1-5 ppm (Japan). Frequent use of some OP insecticides in the USA and Japan has caused their increased tolerance in several midge species. The IGRs, diflubenzuron and methoprene, provide alternate means for midge control. These IGRs in some situations suppressed adult midge emergence by greater than 90% at rates less than 0.3 kg AI/ha. A number of parasites and pathogens have been reported from midges in different parts of the world. Bacillus thuringiensis serovar. israelensis is effective against some midge species, but at rates at least 10x or higher established for mosquito larvicidal activity. The flatworm, Dugesia dorotocephala, and some fish species offer a good potential for midge control in some situations. In large habitats covering hundreds or thousands of ha, information on the basic ecology of larval midges and adult behavior is essential for formulating midge control criteria. More research is needed on the biological and physical and cultural control of these pestiferous insects. PMID- 1895085 TI - Larvicidal activity of Tagetes minuta (marigold) toward Aedes aegypti. AB - The steam distilled oils of 3 species of marigold, Tagetes patula, T. erecta and T. minuta, were tested for larvicidal activity toward third instar Aedes aegypti; activity at 10 ppm was demonstrated only for T. minuta. The larvicidal property of the whole oil dispersed in water persisted for at least 9 days. The terpene, ocimenone, which is a part of the whole oil, was found to be larvicidal only at a higher concentration than the whole oil and to lose its activity within 24 h after dispersal in water. These results suggest a potential utilization of oil of T. minuta or its components for the control of Ae. aegypti and other species of mosquitoes. PMID- 1895086 TI - Vertical distribution of Psychoda alternata (Diptera:Psychodidae) in soil receiving wastewater utilized for turf cultivation. AB - Vertical distribution of immature Psychoda alternata in soil to a depth of 15 cm was studied in Jacksonville, FL. Samples were randomly taken from large circular land areas receiving a brewery wastewater utilized for commercial turf cultivation and included turfed and bare habitats. Total organic matter was quantified at various soil depths. Overall, 88.5 and 95.8% larvae and 91.3 and 94.0% pupae were recovered from the top 2.5 cm of soil at turfed and bare habitats, respectively. The highest concentration of total organic matter at both habitat types was in the top 2.5 cm. There were strong positive relationships between the number of larvae and pupae and total organic matter, indicating highest concentrations of immatures in nutrient-rich topsoil with an abundant supply of larval food. We suggest that insecticidal treatment directed against immature P. alternata breeding in such habitats need not penetrate to a depth of more than a few centimeters to affect almost all of the population of this pestiferous insect. PMID- 1895087 TI - Laboratory evaluation of efficacy of bednets impregnated with pyrethroids. AB - The half-life of an insecticide on a treated object can be used as a crucial test for evaluating the residual effect. On cotton and nylon bednets, the half-life of deltamethrin was 65.6 and 55.4 days, whereas the half-life of permethrin on cotton and nylon bednets was 35.0 and 27.4 days. A deltamethrin-impregnated bednet (10 mg/m2) is effective for 6-7 months and costs less than DDT residual spraying (2g/m2) on the inner walls of rooms. PMID- 1895088 TI - Potential use of scrap expanded polystyrene beads for the control of Aedes triseriatus. AB - The potential use of expanded polystyrene (EPS) beads for control of Aedes triseriatus was tested in the laboratory and the field. Laboratory studies showed that beads present in amounts which persisted throughout a season significantly reduced the emergence of Ae. triseriatus adults by preventing normal eclosion from the pupae. In the field, tree holes containing EPS beads had significantly fewer larvae present than untreated controls. These field data suggest that EPS beads may mechanically prevent oviposition by mosquitoes. PMID- 1895089 TI - Hybridization evidence supporting separate species status for Anopheles albitarsus and Anopheles deaneorum (Diptera: Culicidae) in Brazil. PMID- 1895090 TI - Deet and permethrin as protectants against malaria-infected and uninfected Anopheles stephensi mosquitoes. AB - Deet and permethrin were evaluated as protectants against Plasmodium falciparum infected, P. berghei-infected and uninfected Anopheles stephensi mosquitoes. Deet 50% effective dose (ED50) values were 3.2 micrograms/cm2 for P. falciparum infected and 1.9 micrograms/cm2 for uninfected mosquitoes; permethrin values were 0.5 micrograms/cm2 and 0.6 micrograms/cm2, respectively. Deet ED50 values were 2.3 micrograms/cm2 for P. berghei-infected and 1.3 micrograms/cm2 for uninfected mosquitoes; the permethrin values were both 0.5 micrograms/cm2. There were no significant differences in the protective efficacy of deet or permethrin between malaria-infected and uninfected An. stephensi mosquitoes. PMID- 1895091 TI - Aerially applied, liquid Bacillus thuringiensis var. Israelensis (H-14) for control of spring Aedes mosquitoes in Michigan. AB - Liquid B.t.i. (Vectobac 12AS), when mixed with water at a 1:3 ratio and applied by helicopter at a rate of 1.17 liters B.t.i. (4.68 liters mix) per ha, was 99% effective in a small (mass median diameter on dye cards: 178 microns) droplet size but ineffective (65%) in a large (553 microns) droplet against spring Aedes larvae in snowmelt pools. There were about 6 times as many smaller droplets as larger ones impacting the treated pools, which probably explained the difference in effectiveness for the 2 treatment regimes. Results indicate that liquid formulations of B.t.i. could be aerially applied for spring Aedes control at a considerable cost savings and efficiency over aerially applied, granular formulations. PMID- 1895092 TI - A simple technique for determining relative toxicities of Bacillus thuringiensis var. Israelensis formulations against larval blackflies (Diptera: Simuliidae). AB - A laboratory system for assaying the potency of Bacillus thuringiensis var. israelensis formulations against larval blackflies was developed. An orbital shaker was used to create a water current in 250-ml Erlenmeyer flasks containing the test larvae. This system produced dose-mortality relationships with acceptable statistical parameters. PMID- 1895093 TI - Observations on the flight and mating behavior of Anopheles pseudopunctipennis under insectary conditions. AB - Anopheles pseudopunctipennis showed a bimodal daily pattern in flight activity with the largest peak at 2000 h and the smaller one at 0400 h. In the first 10 days as adults, the maximum swarming activity was observed between 2-6 days of age. Also, sexual encounters were registered at the same time interval. PMID- 1895094 TI - Human natural antibodies to Culex quinquefasciatus: age-dependent occurrence. AB - The titer of anti-Culex quinquefasciatus antibodies which were mostly of IgG and IgE isotypes was determined in humans living in Wuchereria bancrofti endemic regions. A progressive increase in the titer of antibodies was observed with age. In contrast, sera from people living in regions where the Cx. quinquefasciatus is of low prevalence were found to have markedly reduced IgG and almost zero IgE levels. PMID- 1895095 TI - Evaluation of pyrethroids lambda-cyhalothrin, deltamethrin and permethrin against Aedes albopictus in the laboratory. AB - Three pyrethroids were evaluated in the laboratory against Aedes albopictus females by exposure to insecticide impregnated papers, and to 4th instar Ae. albopictus larvae as insecticide solutions. Lambda-cyhalothrin was found to be the most effective pyrethroid when tested against Aedes albopictus adult females and larvae compared with that of deltamethrin and permethrin. PMID- 1895096 TI - Occurrence of Anopheles culicifacies species A in Iran. AB - Polytene chromosome preparations of the ovarian nurse cells of Anopheles culicifacies females collected in 6 different parts of Baluchistan, Iran, during September-October 1987 and May-June 1988 revealed the existence of species A in this country. The chromosome arms are homosequential with those of species A of India. This report confirms the distribution of species A in Iran. PMID- 1895097 TI - Anopheles neomaculipalpus, first record for Guatemala. AB - Anopheles neomaculipalpus is being confirmed in Guatemala for the first time, based on adult females and larvae collected in distinctly different parts of the country. Habitat data are also given. PMID- 1895098 TI - Acetylation of serotonin in the rabbit pineal gland: an N-acetyltransferase with properties distinct from NAT1 and NAT2 is responsible. AB - Two rabbit arylamine N-acetyltransferases (NAT1 and NAT2, EC 2.3.1.5) have been cloned and characterized recently in this laboratory. They catalyze the acetylation of primary arylamine and hydrazine drugs and other substrates in the liver, including sulfamethazine, p-aminosalicylic acid, and p-aminobenzoic acid. In the pineal gland, serotonin is metabolized to N-acetylserotonin by an unknown N-acetyl-transferase. Similarity of the liver enzymes and the pineal gland arylalkylamine N-acetyltransferase (AA-NAT) has been suggested, because pineal gland homogenates were shown to metabolize arylamine substrates as p-phenetidine, aniline, or phenylethylamine, and liver homogenates or partially purified liver enzyme preparations catalyzed the N-acetylation of serotonin. The present study was undertaken to elucidate the possible role of NAT1 or NAT2 in serotonin acetylation in the pineal gland. We transiently expressed rNAT1 and rNAT2 genes in COS cells, studied the kinetics of the enzymes produced with various substrates, and compared these data with activities of rabbit pineal glands and livers. These enzymatic studies were complemented with western blot analysis with antibodies against NAT1 and NAT2. Cross-hybridization of rNAT1 or rNAT2 to the gene for the pineal gland AA-NAT was tested by Southern blot studies of genomic rabbit DNA. Our results indicate that although NAT1 is expressed in the pineal gland, it is not involved in the physiologically important step of N-acetylation of serotonin. PMID- 1895099 TI - The synthesis and release of acetylcholine by depolarized hippocampal slices is increased by increased choline available in vitro prior to stimulation. AB - The objective of these experiments was to determine whether preincubating hippocampal slices with choline provides precursor that can be used during a subsequent incubation to support or enhance the synthesis of acetylcholine (ACh). Slices were preincubated for 60 min with 0, 10, 25, or 50 microM choline, washed, resuspended, and then incubated for 10 min in choline-free buffer containing 4.74 (Krebs-Ringer bicarbonate, KRB) or 25 mM KCl. The tissue contents of ACh and choline were determined prior to and after the preincubation, as well as after the incubation; the amounts of ACh and choline released were measured, and ACh synthesis was calculated. Preincubation in the absence of choline increased the tissue content of ACh to 242% of original levels; preincubation with 10 microM choline did not lead to a further increase, but preincubation with 25 or 50 microM choline increased the ACh content to 272% of original levels, significantly greater than that of slices preincubated with either 0 or 10 microM choline. When tissues were subsequently incubated for 10 min with either KRB or 25 mM KCl, ACh release from slices preincubated with 50 microM choline was greater than from slices preincubated with 0, 10, or 25 microM choline. Incubation of slices with KRB did not alter the tissue content of ACh, but when tissues were incubated with 25 mM KCl, the ACh content of slices preincubated with 0 or 10 microM choline decreased significantly, whereas that of slices preincubated with 25 or 50 microM choline did not.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1895100 TI - Complex interactions between polyamines and calpain-mediated proteolysis in rat brain. AB - Polyamine synthesis is induced by various extracellular signals, and it is widely held that this biochemical response participates in cell growth and differentiation. Certain of the triggers for synthesis in brain tissues also increase the breakdown of high-molecular-weight structural proteins, apparently by activating calcium-dependent proteases (calpains). The present experiments tested the possibility that calpain activity is modulated by polyamines. Spermine, spermidine, and putrescine all increased calcium-dependent proteolysis of [14C]casein by soluble fractions of rat brain. The order of potency was spermine greater than spermidine greater than putrescine, with apparent affinities of 30, 300, and 6,000 microM, respectively. Each of the three polyamines at physiological concentrations also potentiated the calcium-dependent breakdown of two endogenous high-molecular-weight structural proteins known to be substrates of calpain, in both supernatant and membrane fractions. The thiol protease inhibitor leupeptin, a known calpain inhibitor, also inhibited calcium dependent proteolysis in the presence and absence of polyamines. The polyamines did not increase the activity of purified calpain I or calpain II determined with either [14C]casein or purified spectrin as the substrate, nor did they interfere with the inhibitory effects of calpastatin, an endogenous inhibitor of calpain. However, polyamines potentiated the stimulation of endogenous but not purified calpain activity produced by an endogenous calpain activator. These results suggest a role for polyamines in protein degradation as well as protein synthesis. PMID- 1895101 TI - Solubilized rat brain adenosine receptors have two high-affinity binding sites for 1,3-dipropyl-8-cyclopentylxanthine. AB - The specific binding of L-N6-[3H]phenylisopropyladenosine (L-[3H]PIA) to solubilized receptors from rat brain membranes was studied. The interaction of these receptors with relatively low concentrations of L-[3H]PIA (0.5-12.0 nM) in the presence of Mg2+ showed the existence of two binding sites for this agonist, with respective dissociation constant (KD) values of 0.24 and 3.56 nM and respective receptor number (Bmax) values of 0.28 +/- 0.03 and 0.66 +/- 0.05 pmol/mg of protein. In the presence of GTP, the binding of L-[3H]PIA also showed two sites with KD values of 24.7 and 811.5 nM and Bmax values of 0.27 +/- 0.09 and 0.93 +/- 0.28 pmol/mg of protein for the first and the second binding site, respectively. Inhibition of specific L-[3H]PIA binding by 1,3-dipropyl-8 cyclopentylxanthine (DPCPX) (0.1-300 nM) performed with the same preparations revealed two DPCPX binding sites with Ki values of 0.29 and 13.5 nM, respectively. [3H]DPCPX saturation binding experiments also showed two binding sites with respective KD values of 0.81 and 10.7 nM and respective Bmax values of 0.19 +/- 0.02 and 0.74 +/- 0.06 pmol/mg of protein. The results suggest that solubilized membranes from rat brain possess two adenosine receptor subtypes: one of high affinity with characteristics of the A1 subtype and another with lower affinity with characteristics of the A3 subtype of adenosine receptor. PMID- 1895102 TI - Neuronal survival factor from bovine brain is identical to neuron-specific enolase. AB - Neuronal survival factors in the central nervous system were investigated by using a primary culture of embryonic rat neocortical neurons. Bovine hippocampus was homogenized, and the supernatant from high-speed centrifugation was used as the starting material. At the step of DE-52 ion-exchange chromatography, neuronal survival activity was recovered in two fractions, fraction 14 (F14) and fraction 23 (F23). Antisera to the crude F14 and F23 fractions were raised in rabbits. These two antisera completely inhibited the neurotrophic activity of both fractions. Western blotting analysis revealed that anti-F14 antiserum recognized mainly a 30-kDa protein in F14 and anti-F23 antiserum recognized mainly a 44-kDa protein in F23. After sodium dodecyl sulfate-polyacrylamide gel electrophoresis of F23, the 44-kDa protein was cut out from the gel and partial amino acid sequences of the protein fragments were determined. A GenBank data bank indicated that the amino acid sequence of the fragment was identical to that of neuron specific enolase (NSE). In our assay system, commercially available NSE itself possessed neuronal survival activity for the cultured neocortical neurons. The effects of NSE and F23 were inhibited completely by anti-NSE polyclonal antibody. Furthermore, highly purified NSE supported the survival of cultured neurons in a dose-dependent manner, and the neurotrophic effect was inhibited by monoclonal antibody to the NSE. These results strongly suggest that NSE is one of the neuronal survival factors in the central nervous system. PMID- 1895103 TI - Exogenous gangliosides GD1b and GD1b-lactone, stably associated to rat brain P2 subcellular fraction, modulate differently the process of protein phosphorylation. AB - GD1b and GD1b-lactone (GD1b-L) gangliosides bind to the same extent to a P2 crude membrane preparation from rat brain. After 30 min of incubation with 10(-4), 10( 5) and 10(-6) M solutions of ganglioside, 1,800, 450, and 100 pmol of ganglioside/mg of protein, respectively, were found to be stably associated to the P2 fraction. This association modifies the phosphorylation process of the P2 membrane proteins in a dose-dependent manner, the maximal effect being reached at a ganglioside association of 1.85 nmol/mg of protein and in large part at 450 pmol/mg of protein. The effects of GD1b and GD1b-L on the phosphorylation of five proteins, showing apparent molecular masses of 17, 20, 36, 41, and 44 kDa, were different after 0.5 min of phosphorylation reaction as well as after 15 min. After 0.5 min of reaction, in the presence of stably associated GD1b, the phosphorylation of the 36-, 41-, and 44-kDa proteins was increased with reference to the control, whereas the phosphorylation of the 17- and 20-kDa proteins was decreased. GD1b-L exerted qualitatively similar effects only on the 44-, 41-, and 36-kDa proteins and to a strongly reduced degree. After 15 min of reaction, only the phosphorylation of the 36-kDa protein was stimulated by GD1b; GD1b-L exerted a similar effect, but to a low degree. PMID- 1895104 TI - Postnatal age and protein tyrosine phosphorylation at synapses in the developing rat brain. AB - The relationship between postnatal age and protein tyrosine kinase activity in synaptosomes prepared from the rat forebrain was studied. Synaptosomal particulate and soluble fractions, as well as total homogenates, the cell soluble fraction, and P3, were prepared from rats ranging in postnatal age from 5 to 60 days and analyzed for (a) tyrosine kinase activity using polyglutamyltyrosine (4:1) as the substrate, (b) the presence of endogenous substrates for tyrosine phosphorylation using polyclonal antibodies specific for phosphotyrosine, and (c) levels of pp60src. Enzyme activity, expressed per milligram of protein, in the total homogenate, P3, and both the cell and synaptosomal soluble fractions was highest in the brains of young animals (postnatal days 5-10) and decreased thereafter to adult levels. In contrast, tyrosine kinase activity in the synaptosomal particulate fraction exhibited a unique biphasic developmental profile, increasing to maxima at postnatal days 10 and 20 before decreasing to adult values. Endogenous substrates for tyrosine phosphorylation were identified by incubating subcellular fractions with 2 mM ATP in the presence of sodium orthovanadate and probing nitrocellulose blots of proteins separated by gel electrophoresis with antiphosphotyrosine antibodies. Several phosphotyrosine containing proteins were detected in the synaptosomal particulate and P3 fractions, including proteins of Mr 180K, 145K, 120K, 100K, 77K, 68K, 62K, 54K, 52K, and 42K. In the cell soluble fraction a protein doublet of Mr 54/52K and a 120K protein were the major phosphotyrosine-containing proteins. The 54/52K doublet was the major protein tyrosine kinase substrate in the synaptosomal soluble fraction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1895105 TI - Effects of monensin and veratridine on acetylcholine release and cytosolic free Ca2+ levels in cerebrocortical synaptosomes of rats. AB - Monensin (10(-8)-10(-4) M) caused a dose-dependent increase in the release of [3H]acetylcholine ([3H]ACh) from purified rat cerebrocortical synaptosomes, with an EC50 of approximately 1.6 x 10(-6) M. Extracellular Na+, but not Ca2+, was required for a monensin-induced increase in the release of [3H]ACh. Monensin also increased the cytosolic free Ca2+ concentration ([Ca2+]i) and uptake of 22Na+ in a dose-dependent manner. Monensin continued to cause a dose-dependent increase in [Ca2+]i in the absence of extracellular Ca2+, although an approximately 50% reduction was noted at concentrations of greater than 10(-5) M. The EC50 for the monensin-induced increase in [Ca2+]i was similar to that noted in the release of [3H]ACh. Veratridine exhibited effects similar to those of monensin, but a large portion of the increase in [Ca2+]i and [3H]ACh release was dependent on extracellular Ca2+. Measurements of rhodamine 6G fluorescence indicated that monensin and veratridine caused synaptosomal hyperpolarization and depolarization, respectively. Tetrodotoxin (10(-6) M) completely blocked all the effects of veratridine but had no effect on the activity of monensin. These results suggest that monensin increases the release of ACh at least in part by increasing [Ca2+]i, resulting from the increase in the Na+ influx through tetrodotoxin-insensitive mechanisms in rat cerebrocortical synaptosomes. PMID- 1895106 TI - In vivo studies identify 5 alpha-pregnan-3 alpha-ol-20-one as an active anesthetic agent. AB - Mice were anesthetized with 5 alpha-[3H]pregnan-3 alpha-ol-20-one. Brain levels for 5 alpha-pregnan-3 alpha-ol-20-one and its five major metabolites (5 alpha pregnanedione, k0, k1, k2, k3) were compared at behavioral endpoints that are characteristic of the anesthetized state. The results support the hypothesis that 5 alpha-pregnan-3 alpha-ol-20-one mediates the anesthetic response, and they weigh against the hypothesis that any of its metabolites is solely responsible for the onset or the maintenance of the anesthetized state. For an administered dose of 3 mg/kg, brain levels (means +/- SEM) for 5 alpha-pregnan-3 alpha-ol-20 one at the time of the loss of the righting response (n = 10) and at the time of the return of the righting response (n = 6) were 7.24 +/- 0.61 pmol/mg of brain tissue and 3.63 +/- 0.26 pmol/mg of brain tissue, respectively. No metabolite level was lower at the return of the righting response than at the loss of the righting response. 5 alpha-Pregnan-3 alpha-ol-20-one brain levels increased consistently with the percentage of anesthetized mice. This was not the case for any of the metabolites. Fifty percent of the mice were anesthetized when the 5 alpha-pregnan-3 alpha-ol-20-one level was 4.5 pmol/mg of brain tissue. PMID- 1895107 TI - Glutamic acid decarboxylase activity of the preoptic area and hypothalamus is influenced by the serotonergic system. AB - The effect of the serotonergic system on glutamic acid decarboxylase (GAD) activity of the preoptic area and the hypothalamus was studied in female rats on the day of proestrus. A circadian rhythm of GAD activity was observed with higher values in rats killed at 1130 h than in rats killed at 1500 h. In rats bearing lesions of the median raphe nucleus (MRn), a nucleus that sends 5 hydroxytryptamine nerve terminals to the areas under study decreased GAD activity. On the contrary, electrochemical stimulation of the MRn enhanced GAD activity in intact rats killed at 1500 h, but not in those killed at 1130 h, an effect that was prevented by the injection of the 5-hydroxytryptamine antagonist, methysergide. Furthermore, the injection of 5-hydroxytryptamine into the third ventricle, either in intact rats in the afternoon or in MRn-lesioned rats in the morning, also increased GAD activity. The results of the present study suggest that activation of the serotonergic system increases GAD activity in the preoptic area and hypothalamus. PMID- 1895108 TI - Selective and nonselective effects of 1-methyl-4-phenylpyridinium on oxygen consumption in rat striatal and hippocampal slices. AB - Insights into the etiology and pathophysiology of Parkinson's disease may derive from elucidation of the neurotoxic mechanisms of 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) and its active metabolite, 1-methyl-4-phenylpyridinium (MPP+). In previous studies, MPP+ provoked oxidation of cytochrome b and K+ leakage into the extracellular space of rat striatal slices. Magnitudes of these time-dependent responses were far greater than expected had the MPP+ effects been limited to dopaminergic terminals. To determine whether cytochromes become oxidized from K(+)-induced increases in ion transport activity or from electron transport inhibition at complex I, oxygen consumption was measured because this should be increased by the former and decreased by the latter mechanism. Low MPP+ concentrations (1 microM) decreased O2 consumption (approximately 40% in 3 h) in striatal slices. This decrease was diminished by mazindol and did not occur in hippocampal slices. High toxin concentrations (100 microM) inhibited oxygen consumption to a greater extent (approximately 60%) in striatal slices; this inhibition was still greater in hippocampal slices. These results support the hypothesis that acute effects of low ("selective") MPP+ concentrations require the presence of dopaminergic terminals to trigger a sequence of destructive metabolic events but that the metabolic consequences of MPP+ spread to neighboring cells. In contrast, high MPP+ concentrations nonselectively inhibit metabolic and ion transport activity without requiring the presence of dopaminergic terminals. These results also suggest that physiological effects of "selective" MPP+ concentrations extend to nondopaminergic cells. PMID- 1895109 TI - Characterization and localization of a long-chain isoprenyltransferase activity in porcine brain: proposed role in the biosynthesis of dolichyl phosphate. AB - Pig brain microsomes catalyzed the enzymatic transfer of radiolabeled isoprenyl groups from [1-14C]isopentenyl pyrophosphate [( 1-14C]I-P-P) into long-chain polyisoprenyl pyrophosphates (Poly-P-P) and unidentified neutral lipids. The brain isoprenyltransferase activity synthesizing the Poly-P-P (1) required 5 mM Mg2+ and 10 mM vanadate ions for maximal activity; (2) exhibited an apparent Km of 8 microM for I-P-P; (3) utilized exogenous farnesyl pyrophosphate and two stereoisomers of geranylgeranyl pyrophosphate as substrates; (4) was optimal at pH 8.5; and (5) was stimulated by dithiothreitol. The major products were identified as C90 and C95 allylic Poly-P-P on the basis of the following chemical and chromatographic properties: (1) the intact product co-chromatographed with authentic Poly-P-P on silica-gel-impregnated paper; (2) the major product was converted to a compound chromatographically identical to polyisoprenyl monophosphate (Poly-P) by alkaline hydrolysis; (3) treatment of the labeled Poly P with wheat germ acid phosphatase or mild acid yielded neutral labeled products; (4) the KOH hydrolyzed product coeluted with authentic Poly-P from lipophilic Sephadex LH-20; and (5) the labeled lipids produced by enzymatic dephosphorylation had mobilities identical to fully unsaturated polyisoprenols containing 18 (C90) and 19 (C95) isoprene units when analyzed by reverse-phase chromatography. When subcellular fractions from rat brain gray matter were compared, the highest specific activity was found in the heavy microsomes. These results demonstrate that brain contains an isoprenyltransferase activity, associated with the rough endoplasmic reticulum, capable of synthesizing long chain Poly-P-P. The enzymatic reactions by which the Poly-P-P intermediate is converted to dolichyl phosphate remain to be elucidated. PMID- 1895110 TI - Changes in extracellular concentrations of glutamate, aspartate, glycine, dopamine, serotonin, and dopamine metabolites after transient global ischemia in the rabbit brain. AB - Although considerable evidence supports a role for excitatory amino acids in the pathogenesis of ischemic neuronal injury, few in vivo studies have examined the effect of increasing durations of ischemia on the extracellular concentrations of these agents. Recently, other neurotransmitters (e.g., glycine and dopamine) have been implicated in the mechanism of ischemic neuronal injury. Accordingly, this study was undertaken to examine the patterns of changes of extracellular glutamate, aspartate, glycine concentrations in the hippocampus, and dopamine, serotonin, and dopamine metabolites in the caudate nucleus with varying durations (5, 10, or 15 minutes) of transient global cerebral ischemia as evidence to support their pathogenetic roles. Microdialysis was used to sample the brain's extracellular space before, during, and after the ischemic period. Glutamate and aspartate concentrations in the dialysate increased from baseline by 1-, 5-, and 13-fold and by 4-, 9-, and 31-fold, respectively, for the three ischemic durations. The concentrations returned to baseline rapidly after reperfusion. The peak concentrations of glutamate and aspartate were significantly higher with increasing ischemic duration. Dopamine concentrations increased by approximately 700-fold in response to all three ischemic durations and returned to baseline within 10 min of reperfusion. Glycine, in contrast, increased during ischemia by a mean of 4-fold, but remained elevated throughout the 80-min period of reperfusion. The final concentrations of glycine were significantly higher than baseline levels (p = 0.0002, Mann-Whitney test). That glutamate and aspartate concentrations in the hippocampus co-vary with the duration of global ischemia is taken as supportive evidence of their pathogenetic role in ischemic neuronal injury.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1895111 TI - Identification and immunolocalization of phospholipase C in bovine rod outer segments. AB - Bovine rod outer segments (ROS) contain a phospholipase C (PLC) that hydrolyzes phosphatidylinositol 4,5-bisphosphate. Approximately 60-70% of PLC activity is recovered in soluble extracts of ROS. Moreover, the specific activity of this soluble PLC is approximately 10-fold higher than that of resealed ROS enzyme activity. Peptide-specific antiserum (Ab 1109) directed against a highly conserved sequence of the Y-region found in several PLC isozymes was used to detect any PLC belonging to this family. This antibody specifically recognized a protein of apparent molecular mass of approximately 140 kDa present in immunoblots of soluble extracts of both ROS and whole retina. The elution profile of this 140-kDa antigen from a Sephadex G-150 column coincided with the peak of PLC activity, suggesting PLC activity is associated with the 140-kDa protein. Immunocytochemical studies of bovine retina using Ab 1109 showed pronounced immunoreactive labeling in the photoreceptor layer. In resealed ROS and washed ROS membranes, Ab 1109 recognized an additional protein of apparent molecular mass of 70 kDa not usually detectable in soluble extracts of ROS, suggesting the presence of at least two isozymes of PLC in ROS. PMID- 1895112 TI - Botulinum neurotoxin light chain inhibits norepinephrine secretion in PC12 cells at an intracellular membranous or cytoskeletal site. AB - Botulinum neurotoxin (NT) is a potent inhibitor of neurotransmitter secretion, but its intracellular mechanism and site of action are unknown. In this study, the intracellular action of NT was investigated by rendering the secretory apparatus of PC12 cells accessible to macromolecules by a recently described "cell cracking" procedure. Soluble cytoplasmic factors were depleted from permeabilized cells by washing to generate cell "ghosts" which retained cellular structural components and intracellular organelles (including secretory granules). The PC12 cell ghosts exhibited Ca(2+)-activated [3H]norepinephrine release which was enhanced by cytosolic proteins and MgATP. PC12 cell ghosts provide the opportunity to distinguish the intracellular action of NT on soluble cytoplasmic components versus structural cellular components. The 150-kDa NT and the 50-kDa light chain of serotypes E and B, and to a lesser extent type A, inhibited Ca(2+)-activated [3H]norepinephrine release in PC12 ghosts, but not in intact PC12 cells. The 100-kDa heavy chain had no effect. This indicates that NT acts at an intracellular site in these cells permeabilized by "cell cracking." The inhibition of secretion by NT was rapid and irreversible under the incubation conditions used. NT inhibition of [3H]-norepinephrine release from PC12 ghosts occurred in the absence of cytosolic proteins and MgATP and was not reversed by the addition of cytosolic proteins and MgATP, indicating that NT acts at an intracellular membranous or cytoskeletal site. PMID- 1895113 TI - Membrane-associated phospholipase D activity in rat sciatic nerve. AB - Rat sciatic nerve contains a membrane-bound phospholipase D that catalyzes the hydrolysis of exogenous phosphatidylcholine (PC) to phosphatidic acid (PA) and choline. The enzyme is associated with a particulate fraction consisting primarily of microsomes and myelin. This fraction also contains phosphatidate phosphohydrolase activity leading to the production of diacylglycerols (DAG). The phosphohydrolase activity can be completely inhibited by NaF. Hydrolysis of exogenous PC requires detergent and is linear up to about 40 micrograms of protein at a pH optimum of 6.5. In the absence of NaF, the sum of PA and DAG increases linearly for 40 min, whereas in its presence, PA production is linear for only 15 min. At optimum conditions, PC hydrolysis proceeds at 15 nmol/h/mg of protein. Addition of increasing amounts of ethanol to the incubation system leads to the generation of increasing amounts of phosphatidylethanol, indicating transphosphatidylation activity. At an ethanol concentration of 0.4 M, phosphatidylethanol represents about one-half of the reaction products generated at approximately the same rate of enzymic activity observed in the absence of ethanol. Higher ethanol concentrations are inhibitory. PMID- 1895114 TI - Quantitative and qualitative alterations of neuronal and glial intermediate filaments in rat nervous system after exposure to 2,5-hexanedione. AB - The precise mechanism for the neurotoxicity of 2,5-hexanedione is not known, but cross-linking of neurofilament proteins has been suggested as one possibility. In this study the effects of long-term exposure to 2,5-hexanedione were studied in the rat nervous system with special reference to regional changes in the quantities of neuronal and glial intermediate filaments. Using enzyme-linked immunosorbent assays the concentrations of 68- and 200-kDa neurofilament polypeptides were shown to be reduced in all brain regions studied. Similar results were obtained in the sciatic nerve. The concentration of glial fibrillary acidic protein was decreased in the cerebellar vermis and the dorsal cerebral cortex, whereas it was increased in the spinal cord, a result suggesting a regional variation in glial sensitivity. The intermediate filaments of the exposed animals were also immunoblotted using polyclonal antisera against the various neurofilament polypeptides and glial fibrillary acidic protein. In all tissues studied, several aggregates with molecular weights higher than those of the monomeric polypeptides were demonstrated. Contrary to clinical observations, these data indicate pronounced effects in both CNS and PNS and call for further studies on CNS effects in humans. PMID- 1895115 TI - Identification of B2 bradykinin binding sites on cultured cortical astrocytes. AB - Bradykinin was found to bind to specific high-affinity sites in cultured cortical astrocytes from rat brain, and this binding appeared to be specific for the B2 bradykinin receptor subtype. Nonlinear regression analysis of saturation experiments using a computer programme revealed a single KD of 16.6 +/- 2.6 nM and a Bmax of 352.2 +/- 30.7 fmol/mg of protein. These results indicate that astrocytes possess bradykinin receptors and that these are predominantly of the B2 subtype. PMID- 1895116 TI - Defining prognosis in medical coma. PMID- 1895117 TI - Cysts of the neuraxis of endodermal origin. AB - Five colloid cysts of the third ventricle were compared with two spinal enterogenous cysts to examine the hypothesis that these entities have the same origin from primitive endodermal tissue. All the lesions showed cuboidal and columnar epithelium with mucus containing goblet cells and cilia. Immunohistochemistry for cytokeratin, EMA and CEA was positive in all the colloid cyst and enterogenous cyst epithelium. S-100 was focally positive in three of the colloid and one of the enterogenous cysts while vimentin and GFAP were negative in both. The anatomical distribution of both colloid and enterogenous cysts is reviewed. An illustrative case of an identical cyst within the fourth ventricle is presented. This suggests that the similarities between colloid and enterogenous cysts and the presence of identical lesions along the neuroaxis indicate that these structures are derived from primitive foregut endoderm. PMID- 1895118 TI - Albucasis or Abul Kasim (936-1013). PMID- 1895119 TI - Cerebral infarction in young people. A study of 148 patients with early cerebral angiography. AB - The aetiology of strokes was studied in a hospital based series of patients aged up to 40 years with precise clinical and radiological criteria. One hundred and forty five patients (75 males and 73 females) aged five to 40 years with cerebral ischaemia were evaluated. Aetiology was heterogeneous and could be classified into seven groups. Cerebral arteriograms were performed in all cases and indicated the aetiological diagnosis in most patients. Embolism was the most frequent recognised abnormality (38.4%). There were no complications of arteriography. Arterial dissections discovered by arteriography were the cause of the stroke in 10.1% of the patients. Atherosclerosis was diagnosed in 32 cases and was the commonest cause (21.6%). In one fifth of cases no cause was found. Contraceptive drugs were considered as potential cause of ischaemic stroke in 11.5%, cardiac diseases in 12.8% and haematological disorders in 8.1%. Other potential causes included migraine, inflammatory diseases, pregnancy and lacunas. Follow up in 126 cases showed that many patients had good functional recovery. PMID- 1895120 TI - Prospective neuropathological validation of Hachinski's Ischaemic Score in dementias. AB - The sensitivity and specificity of Hachinski's Ischaemic Score (IS) in the diagnosis of the vascular aetiology of dementia was studied in a series of 32 demented patients, dementia of the Alzheimer type (16), multi-infarct dementia (7), mixed dementia (6), Pick's disease (3), with neuropathological diagnosis as the point of reference. The IS distinguished between primary degenerative dementia and multi-infarct or mixed dementia. As single features of the IS "a positive history of stroke" and "a fluctuating course" showed differing prevalences in the latter two diagnostic categories. The IS labelled 21% of patients with primary degenerative dementia as having a vascular aetiology. The uncritical application of the IS to large samples in epidemiological studies may cause incorrect labelling of a significant proportion of patients with primary degenerative dementia as vascular dementia. These results are based on observations of long-term inpatients and depend on neuropathological criteria. While the definite diagnosis of DAT by threshold criteria concerning plaque and tangle counts is well established, neither clinical nor pathological evidence of stroke necessarily means that cerebrovascular disease has anything to do with a patient's dementia. PMID- 1895121 TI - A prospective study of physical trauma and multiple sclerosis. AB - During an eight year period 170 multiple sclerosis (MS) patients and 134 controls without physical impairment were followed closely to record all episodes of physical trauma and to measure their effect on exacerbation rate and progression of MS. There was a total of 1407 instances of trauma, which were sorted into various categories. Overall there was no significant correlation between all traumas and disease activity. There was, however, a statistically significant negative correlation between traumatic episodes and exacerbations in 95 patients who had exacerbations during the programme, due primarily to less activity of the disease during a three month period following surgical procedures and fractures. Electrical injury had a significant positive association with exacerbation using a three month at-risk period, but there were no other significant positive correlations in any other category of trauma, including minor head injuries; there were no cases of head injury with prolonged unconsciousness. There was no linkage between the frequency of trauma and progression of disability. MS patients had two to three times more trauma than controls. PMID- 1895122 TI - Cavernomas of the central nervous system: clinical and neuroimaging manifestations in 47 patients. AB - Forty seven cases of central nervous system cavernous angioma (21 males and 26 females) are described. The main clinical signs were epilepsy and brainstem syndromes. Digital subtraction intra-arterial angiography, when used, failed to reveal cavernoma. CT detected many of the lesions, but the most successful supplementary diagnostic procedure was MRI which produces highly characteristic images of cavernous angioma. The diagnosis of cavernous angioma was confirmed in the 18 cases in which the tumour was removed surgically. PMID- 1895123 TI - Cerebral haemorrhage in a French prospective population study. AB - The incidence of cerebral haemorrhage was studied from a population-based stroke registry. The incidence was 12.3 per 100,000 per year in women and 13.9 per 100,000 per year in men, with a peak in the eighth decade and a male preponderance. Haemorrhages were deep seated and mostly due to hypertension. Recognised clinical characteristics of haemorrhage are acute onset, convulsion, vomiting, and disturbed consciousness. This study showed that cerebral haemorrhage may present with pure motor deficit or transient deficit preceding the stroke. The mortality was 51% in the first month, and 61% by two years. PMID- 1895124 TI - Square wave jerks in parkinsonian syndromes. AB - The frequency of square wave jerks (SWJ) was compared in eight patients with progressive supranuclear palsy (PSP), 25 patients with multiple system atrophy or Parkinson's disease plus (MSA/PP), 85 patients with idiopathic Parkinson's disease (PD) and 20 age-matched normal volunteers. In the control group, the mean (SD) SWJ frequency (SWJ larger than 1 degree amplitude) was 2.3 (2.4)/min. Abnormal ocular fixation (SWJ frequency greater than 10/min) was observed in a large proportion of PSP patients (7/8) and of MSA/PP patients (16/25) but in few PD patients (13/85). In the group of PD patients with abnormal ocular fixation, freezing of gait, falls and instability were more severe than in the group of PD patients with normal fixation. The study of ocular fixation may help to differentiate PD clinically from other Parkinsonian syndromes. SWJ are probably not related to the central degeneration of the dopaminergic nigrostriatal pathway observed in PD. PMID- 1895125 TI - Dopaminergic induced changes in cognitive and motor processing in Parkinson's disease: an electrophysiological investigation. AB - Event-related potentials and reaction time measures to auditory discrimination tasks of graded difficulty were used to separate cognitive from motor processing time in 27 patients with newly diagnosed, previously untreated Parkinson's disease and later on optimal levodopa treatment. Before treatment event-related potential P3 and task performance were normal but the reaction time was prolonged compared with age matched controls. After treatment P3 latency was significantly prolonged and the reaction time reduced suggesting a dopamine induced dissociation between cognitive and motor processing. In early Parkinson's disease cognitive processing time remains normal but the motor processing time is prolonged. Dopamine replacement is followed by significantly reduced motor processing time despite increased cognitive processing time. Motor processing may reflect the dopamine status of the putamen whereas dopaminergic over-stimulation of other regions may adversely affect cognitive processing in patients treated with levodopa. PMID- 1895126 TI - Primary meningeal B lymphoma presenting as a subacute ascending polyradiculoneuropathy. AB - A subacute ascending polyradiculoneuropathy was the main feature of a primary meningeal B lymphoma in two patients. Tumour cells appeared in the CSF eight and six months respectively after the onset of the disease. Treatment by intrathecal methotrexate resulted in transient improvement. PMID- 1895127 TI - Mid-brain pathology of Wilson's disease: MRI analysis of three cases. AB - MRI scans were obtained from three patients with Wilson's disease, all of whom showed rigidity and dysarthria; two also showed tremor and dystonia. Two had been treated with D-penicillamine for seven and 14 years, respectively and their neurological abnormalities had improved, but the third patient had not been treated. T2-weighted MRI of the mid-brain in all three revealed the characteristic "face of the giant panda" sign, consisting of high signal intensity in the tegmentum except for red nucleus, preservation of signal intensity of the lateral portion of the pars reticulata of the substantia nigra and hypo-intensity of the superior colliculus. The clinical significance of these MRI abnormalities is discussed. PMID- 1895128 TI - Anterograde amnesia with fornix damage following removal of IIIrd ventricle colloid cyst. AB - Two patients developed anterograde amnesia following the apparently uncomplicated transcallosal-transventricular removal of a colloid cyst. Damage to the fornical columns was demonstrated on CT and MRI scans, whilst other memory related structures were entirely normal. Longitudinal neuropsychological evaluation, over 12-24 months, has revealed a very similar pattern of deficit in the two cases: verbal memory has remained persistently impaired whilst nonverbal anterograde memory has improved to some degree. Formal tests of remote public (famous faces and events) and personal autobiographical memory have supported the clinical impression that neither patient has a temporally extensive retrograde amnesia. These findings address the role of the fornix, and the dissociation of memory processes in humans. PMID- 1895129 TI - Psychosis following temporal lobe surgery: a report of six cases. AB - Six consecutive patients who had had temporal lobe surgery for epilepsy, and been referred for psychiatric assessment of psychotic symptoms, are reported. Their symptoms (a delusional depression, four schizophrenia-like illnesses, and a case of Capgras' syndrome) are discussed in relation to the possible role of their operations, all of which were on the right hemisphere. PMID- 1895130 TI - Clinical and CT correlates in the diagnosis of intracranial tumours. AB - The correlation between clinical and CT findings in cerebral tumours was prospectively studied in 1191 consecutive referrals for cerebral CT. CT revealed a mass lesion in 51 cases (4.3%): 32 neoplasms, five haematomas and one abscess. The diagnostic specificity of CT for neoplasmic tumours was 86% (32 of 37). The clinical suspicion of a cerebral neoplasm was correct in 25 cases (78%) and the clinical localisatory hypothesis was correct in 20 cases (63%) of the neoplasms. A cerebral tumour was found in 5% (11 out of 226) of patients investigated for their first seizure and in 1% (two of 207) investigated for headache without clinical signs. PMID- 1895131 TI - Postradiation lower motor neuron syndrome presenting as monomelic amyotrophy. AB - Monomelic amyotrophy developed 16 months, nine and 12 years after irradiation of the lumbosacral spinal cord for seminoma in one patient and for Hodgkin's disease in two others. In two patients, involvement was clinically limited to one leg, with a subacute course followed by plateau in the first case and with progressive worsening in the second one. In the third patient, the course was progressive with involvement of the other lower limb occurring five years later. From clinical and electrophysiological data, it seems probable that the disease process was a result of a selective injury to the lower motor neuron in the lower spinal cord. PMID- 1895132 TI - Ipsilateral hemi-parkinsonism secondary to an astrocytoma. PMID- 1895133 TI - Spontaneous intraneural haematoma of the optic nerve. PMID- 1895134 TI - Displaced Torkildsen's shunt: an unusual cause of cervical myelopathy. PMID- 1895135 TI - Guillain-Barre syndrome associated with idiopathic thrombocytopenic purpura. PMID- 1895136 TI - Isolated cerebellar syndrome: an atypical form of cerebral malaria. PMID- 1895137 TI - Hemiageusia: an unusual presentation of multiple sclerosis. PMID- 1895138 TI - Paroxysmal kinesigenic choreoathetosis as presenting symptom of multiple sclerosis. PMID- 1895139 TI - Cervical myelopathy due to calcium pyrophosphate dihydrate deposition disease. PMID- 1895140 TI - Acid maltase deficiency presenting with a myopathy and exercise induced urinary incontinence in a 68 year old male. PMID- 1895141 TI - Depression in Parkinson's disease. PMID- 1895142 TI - Episodic paroxysmal hemicrania. PMID- 1895143 TI - Persistence of Theiler's virus infection following promotion of central nervous system remyelination. AB - Chronic infection of SJL/J mice with the Daniel's strain of Theiler's virus develop primary demyelination, viral persistence but minimal central nervous system (CNS)-type remyelination. In contrast, treatment of virus-infected mice with sera or immunoglobulin G (IgG) from mice immunized with homogenized spinal cord (SCH) emulsified in incomplete Freund's adjuvant promotes CNS remyelination. We measured levels of infectious virus, virus antigen and virus-specific antibody to determine if treatments which promote CNS remyelination are able to modulate infection. Levels of virus-specific antibody were higher in mice treated with SCH/IgG than control treatment groups and correlated positively with extent of remyelination. Although number of virus antigen-positive cells in spinal cord was less in mice treated with SCH/IgG than mice treated with phosphate buffered saline (PBS)/IgG, there was only a slight negative correlation with extent of remyelination by regression analysis. Titers of infectious virus isolated three to six months following infection were not different among treatment groups. Even though treatment of mice with SCH/IgG reduced number of virus antigen-positive cells and enhanced levels of virus-specific antibody, CNS remyelination can occur despite presence of infectious virus. PMID- 1895144 TI - Neuropathology of bovine beta-mannosidosis. AB - beta-Mannosidosis, an inherited defect of glycoprotein catabolism previously identified in goats and humans, has been recently diagnosed in Salers cattle. This disorder is associated with deficiency of lysosomal beta-mannosidase and accumulation of oligosaccharides. Analysis of bovine beta-mannosidosis neuropathology was initiated to determine whether independently arising gene defects in cattle and goats result in expression of similar lesions. Brain, spinal cord, and selected peripheral nerves from seven affected newborn Salers calves and three normal newborn calves were available for gross, light microscopic, and electron microscopic analysis. Gross examination revealed hydrocephalus of variable severity and myelin deficiency in the cerebral hemispheres, cerebellum, and brainstem. Microscopic examination revealed cytoplasmic vacuolation, myelin deficiency, and axonal spheroids of similar type and distribution to that reported in affected goats. Cytoplasmic vacuolation resulting from lysosomal storage showed consistent variation among cell types. Myelin deficits were more severe in the cerebral hemispheres and cerebellum than in the spinal cord. Axonal spheroids occurred in the cerebrum, brainstem, cerebellum, and trigeminal nerve endings. The presence of similar lesions in bovine and caprine beta-mannosidosis supports a direct relationship with the gene defect. PMID- 1895145 TI - The long distance effects of brain lesions: visualization of axonal pathways and their terminations in the human brain by the Nauta method. AB - This study aims at determining the reliability and the optimal post-injury survival time for the application of the Nauta technique to the analysis of the human brain. The Nauta method reveals the degeneration not only of nerve fibers, myelinated and unmyelinated, but also of their terminations. Immunohistochemical and ultrastructural observations appear to prove that the Nauta technique indeed stains axons in human autopsy material. The optimal survival time for the use of the Nauta method was found to be between nine days and five months. In cases with longer survival times--up to 20 months--the Nauta technique and a previously proposed polarizing technique (showing birefringent breakdown products of myelin) can be used as complementary methods. Applying these techniques to the human brain may help define the anatomical basis of neurological and neuropsychological symptoms important for man. PMID- 1895146 TI - Uncompacted inner myelin lamellae in inherited tendency to pressure palsy. AB - Nerves in patients with inherited tendency to pressure palsy (ITPP) are susceptible to degrees of traction or compression which in nonaffected persons do not induce neuropathic symptoms or deficits, conduction block of fibers, or electromyographic changes characteristic of the disorder. Two observations suggest a widespread asymptomatic abnormality of nerves: 1) low conduction velocity of clinically unaffected nerves, and 2) focal thickenings (tomacula) on teased myelinated fibers of clinically unaffected sural nerves. Sural nerves from five patients and five healthy subjects were assessed for morphologic abnormality in ITPP that might account for the susceptibility of nerves to compression. Teased nerve fibers showed a higher frequency of segmental demyelination or remyelination, or both (p less than 0.003). The mean frequency of fibers showing focal myelin thickenings was 57 +/- 10% in ITPP and 0% in controls. In electron micrographs, regions of uncompacted myelin lamellae, usually affecting the innermost lamellae and extending for a variable distance averaging 9 +/- 4 microns were seen in 11 +/- 4% of fibers in ITPP. None were found in the control nerves. The finding of uncompacted myelin lamellae may suggest an abnormality of myelin composition or of interaction of Schwann cells and axons accounting for the increased susceptibility to pressure palsy, tomaculous formation, or demyelination. From electron microscopic evaluation of serial skip sections we infer that myelin of tomaculae is in continuity with internodal myelin and is reduplicated (full-thickness or cleaved layers are longitudinally or circumferentially folded-back on themselves). PMID- 1895147 TI - Ecogenetics, xenobiotic biochemistry and neurological disease. PMID- 1895148 TI - Brain stem atrophy in Joseph disease: a morphometric study using two-dimensional (area) measurement by computed tomography. AB - Eight Japanese patients with Joseph disease were studied using computed tomography (CT). Morphometric analysis using the two-dimensional (area) measurement by CT was performed in the infratentorial region. The brain-stem index, an index of brain-stem atrophy or pontine atrophy, revealed a significant decrease (P less than 0.01), with a mean of 66.7% when compared with 16 control subjects. The patients showed a significant increase (P less than 0.01), with a mean of three times that of the controls in the fourth ventricular index, an index of fourth ventricular dilatation. There were no differences in the cerebellar index, an index of cerebellar atrophy, between these patients and the controls, although the patients had an increased number of visible cerebellar vermian (2.0, SD 0.7) and hemispheric sulci (2.6 SD 0.6) as compared with the controls (vermian sulci: 0.4, SD 0.7: hemispheric sulci: 0). These data indicate severe pontine atrophy, fourth ventricular dilatation with mild involvement of the cerebellum and correlate well with the common pathological features of Joseph disease. The present morphometric evaluation by CT may be useful in the clinical diagnosis of Joseph disease. PMID- 1895149 TI - Cardiovascular reflexes and autonomic dysfunction in Parkinson's disease. AB - Cardiovascular reflexes were analysed in a group of 20 patients suffering from Parkinson's disease and in 12 age-matched healthy subjects, in order to ascertain the incidence and degree of autonomic dysfunction. The following were measured: heart rate variation during normal breathing, postural change (30/15 ratio) and during the Valsalva manoeuvre: blood pressure variation after standing. These measurements were taken at least 12 h after therapy had been withdrawn and were repeated after therapy had been resumed. Significant changes in the different heart rate variation indices were found in the parkinsonian patients which correlated with the duration and severity of the extrapyramidal symptomatology. After standing the patients showed a significant drop in blood pressure, when compared respectively with their base values and with the response in controls. Anticholinergic drugs had no significant effect on the heart rate variation indices, whereas antiparkinsonian therapy seems to have contributed to the drop in blood pressure after standing. PMID- 1895150 TI - Parvalbumin-immunoreactive neurons in the cortex in Pick's disease. AB - Parvalbumin (a calcium-binding protein)-immunoreactive (PV-Ir) neurons in the cerebral cortex were examined in 20 postmortem brains obtained from elderly controls and patients with Pick's disease (PD). The type of PV-Ir neurons and their distribution in control and PD brains were similar. The number of PV-Ir neurons in PD brains did not differ significantly from that in the control brains either. These findings suggested that PV-Ir neurons in the cortex are not affected in PD brains. A significant loss of PV-Ir neurons has already been reported in brains obtained from patients with Alzheimer-type dementia (ATD), and the present results suggest the possibility that the damage of PV-Ir neurons might be comparatively selective for ATD brains. PMID- 1895151 TI - Brain-stem auditory evoked potentials and blink reflex in Friedreich's ataxia. AB - The brain-stem involvement in Friedreich's ataxia (FA) was studied by using brain stem auditory evoked potentials (BAEPs) and the blink reflex. Ten out of 18 patients had abnormal BAEPs, the main abnormality being complete absence of responses and disappearance of wave V. Combined degeneration of the peripheral and central acoustic pathways probably accounts for these findings. The blink reflex was abnormal in 50% of the cases. The outstanding abnormality was bilateral delay of late responses with normal early response, which could be correlated with the known pallor of the descending trigeminal tracts. In contrast with BAEP findings, blink reflex abnormalities did not correlate with either the age of patients or the severity and duration of the disease. These data suggest a difference in susceptibility to degeneration between the auditory system and neuronal system subserving the blink reflex. We conclude that systematic BAEP and blink reflex recording is useful in the electrophysiological evaluation of FA patients. PMID- 1895152 TI - Amplification of the c-erbB oncogene is associated with malignancy in primary tumours of neuroepithelial tissue. AB - In various primary brain tumours of neuroepithelial tissue recombinant DNA techniques were used to demonstrate changes of the epidermal growth factor receptor gene, which is homologous to the c-erbB oncogene. Twenty-one of 40 grade III/IV tumours, but only 1 of 16 grade I/II tumours were found to contain amplified and/or rearranged c-erbB sequences. This highly significant difference suggest that c-erbB amplification, rearrangement, or both, are important steps in malignant transformation in a subset of patients with neuroepithelial tumours. PMID- 1895153 TI - Determination of erythrocyte-bound acetylcholinesterase activity for monitoring pyridostigmine therapy in myasthenia gravis. AB - Monitoring of pyridostigmine therapy in patients with myasthenia gravis is not routinely performed, since the daily pyridostigmine doses are adjusted to the patient's actual clinical status rather than to pyridostigmine plasma concentrations (PPC). Moreover, PPC determination is time-consuming and needs much technical equipment. Since pyridostigmine reversible blocks acetylcholinesterase (AChE) at the neuromuscular junction, we studied the correlation between the enzyme's blood activity (erythrocyte-bound AChE) and PPC, on the one hand, and between blood AChE activity and the clinical status of the individual patient, on the other. In five previously untreated patients with myasthenia gravis blood AChE activity decreased in accordance with the actual PPC after a single oral dose of 60 mg pyridostigmine (group A). Amelioration of the clinical status corresponded to the decrease of AChE activity in the same way. In another five patients, who were on stable pyridostigmine medication for at least 1 week, AChE activity and PPC were constant during the day (group B). Since it is easier to perform than PPC, our results suggest that the determination of AChE activity may be superior to measuring PPC for monitoring cholinesterase inhibitor therapy in selected cases. PMID- 1895154 TI - Intrathecal vincristine: a fatal chemotherapeutic error with devastating central nervous system effects. PMID- 1895155 TI - Isolated angiitis of the central nervous system: involvement of penetrating vessels at the base of the brain. AB - Isolated angiitis of the central nervous system (IAC) was diagnosed in a 40-year old Caucasian male by histological examination of a leptomeningeal biopsy specimen, and the exclusion of systemic inflammatory or infective disease. Therapy with prednisone 30 mg/day and cyclophosphamide 100 mg/day resulted in clinical and radiological improvement, which have been maintained for an 8-month follow-up period. Magnetic resonance imaging (MRI) showed lesions implicating involvement of specific penetrating vessels at the base of the brain, an unusual complication of IAC, and allowed an accurate MRI-clinical correlation. PMID- 1895156 TI - Subacute AIDS-related lumbosacral radiculopathy: a bacterial infection? AB - A case of lumbosacral polyradiculitis in an HIV-1-positive man (CDC IIB) leading to a flaccid paraplegia below the level of L4 is reported. A detailed analysis of several cerebrospinal fluid samples led to the suspicion of a bacterial infection. After treatment with antibiotics and tuberculostatic agents the neuropathy improved and the patient has survived for 2 years. In contrast to similar cases that were probably caused by cytomegalovirus in terminal stages of AIDS, it is argued that an unidentified bacterial infection was the cause of the polyradiculitis in the present case. PMID- 1895157 TI - Discordance for late-onset degenerative ataxia in monozygous triplets. PMID- 1895158 TI - A brain-stem lesion in the Miller Fisher syndrome demonstrated by CT and MRI. PMID- 1895159 TI - A monoclonal antibody (ERIC-1), raised against retinoblastoma, that recognizes the neural cell adhesion molecule (NCAM) expressed on brain and tumours arising from the neuroectoderm. PMID- 1895160 TI - BCNU stability as a function of ethanol concentration and temperature. AB - BCNU is increasingly used in low ethanol (ETOH) concentrations, 5% dextrose-water (D5W), or normal saline (NS) solutions, especially for intra-arterial and prolonged (e.g., 3 day) intravenous (IV) infusions. Little work, however, has been done to evaluate BCNU decomposition rates in concentrations, diluents, and temperatures similar to those employed clinically. This study examined BCNU solutions in ETOH, NS, and D5W to evaluate, conclusively, initial recovery and decomposition rates in these three diluents. Initial BCNU recovery rates were: 95.6 +/- 0.3% (100% D5W), 89.6 +/- 0.5% (15% ETOH), and 85.2 +/- 0.5% (NS) (P less than 0.001). Study of all solutions revealed no measurable BCNU decomposition over 24 hrs (0 degrees C) and no significant difference in decomposition rates between any of the diluents (19.5 degrees C). At 37 degrees C, the solutions showed different half-lives: 14.3 +/- 0.19 hrs (15% ETOH), 10.6 +/- 0.02 hrs (10% ETOH), 8.2 +/- 0.21 hrs (5% ETOH), 7.3 +/- 0.06 hrs (NS), and 6.8 +/- 0.07 hrs (D5W) (P less than 0.001). Decomposition rates between all three temperatures (19.5 degrees C, 37 degrees C, and 50 degrees C) were significantly different (P less than 0.01) for each diluent. Dissolving BCNU powder into either D5W or NS required only 5 min when hand-shaken at body temperature. This study of initial recovery and decomposition rates suggests that, although BCNU decomposition rates were significantly increased at body temperature (37 degrees C), it was quite low and essentially unaffected by different diluents at room temperature (i.e., 19.5 degrees C).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1895161 TI - On the significance of Lhermitte's sign in oncology. AB - We present three cases of Lhermitte's sign out of twenty consecutive cases of epidural spinal cord compression due to metastatic cancer. The three patients were diagnosed with epidural thoracic compressions. The literature on Lhermitte's sign is reviewed with emphasis on the differential diagnosis of this symptom in oncological patients. PMID- 1895162 TI - The effect of age on the latency of radiation myelopathy. AB - The latent period to forelimb paresis following photon irradiation of the cervical spinal cord was evaluated in Sprague-Dawley rats ranging in age from 9 days to adulthood. The radiation was administered dorsally in single fractions, and in 15-day-old animals, to different lengths of the rostral cord and in doses ranging from 16 to 38 Gy. The duration of the latent period was found to be directly proportional to the age of the animal at the time of irradiation, and independent of radiation dose or the volume of the cervical cord which was irradiated. In the majority of paretic animals, the irradiated segment of the spinal cord demonstrated white matter necrosis. The results indicate that in the developing rat, the manifestations of radiation myelopathy are delayed by an interval determined in part by the age of the animal at the time of irradiation. PMID- 1895163 TI - Brain lesions following combined treatment with methotrexate and craniospinal irradiation. AB - Eight patients with meningeal seeding by carcinoma or lymphomas were treated with intravenous (i.v.) and/or intrathecal (i.th.) Methotrexate (MTX). Seven patients received additional craniospinal irradiation and in all seven a fatal encephalopathy developed. On the bases of clinical and morphological findings we identified an acute and a delayed form of encephalopathy and concluded that the concurrent administration of Methotrexate and of craniospinal irradiation increases considerably the risk of brain damage. PMID- 1895165 TI - Effects of induced hypertension on blood flow and capillary permeability in rats with experimental brain tumors. AB - To study the possibility of enhancing the delivery of antineoplastic agents to tumor tissue, we conducted an experimental study using induced hypertension with angiotensin II in rats with experimental brain tumors. Drug delivery was evaluated by measuring local cerebral blood flow (LCBF) and regional cerebral capillary permeability with quantitative autoradiography. There was no significant difference of LCBF in the central region of tumor tissue between the control group and the induced hypertension group. LCBF in the peripheral region of tumor tissue in the induced hypertension group was significantly higher than that in the control group. On the other hand, despite induced hypertension, no significant changes in the regional cerebral capillary permeability were observed between the groups. These results indicate that delivery of the lipid-soluble antineoplastic agents, which depend upon cerebral blood flow, can be enhanced by induced hypertension. PMID- 1895164 TI - The therapy of primary brain lymphoma. AB - Recommendations regarding the current therapy of primary brain lymphoma (NHL-CNS) take into account the occurrence of this tumor in immunocompetent and immunosuppressed hosts. Immunohistochemical evaluation of biopsy material or spinal fluid provides the diagnosis in 90% of patients. For the immunocompetent, pre-irradiation intra-venous or intra-arterial chemotherapy with Methotrexate alone or in combination with other agents is provided to treat tumor within multiple brain sites. Subarachnoid deposits are treated with Methotrexate by intrathecal administration. Radiation is provided after chemotherapy and for the treatment of vitreal/retinal deposits or symptomatic lesions within the spinal axis. The therapy of recurrent NHL-CNS makes use of intravenous Methotrexate or high dose Cytosine Arabinoside. Immunosuppressed patients respond to reduction of immunosuppressive medication. The therapy of NHL-CNS in the AIDS patient makes use of corticosteroids followed by cranial irradiation. A discussion of emerging trends in the therapy of NHL-CNS in the AIDS and non-AIDS population is provided. PMID- 1895166 TI - Thermal enhancement of ACNU and potentiation of thermochemotherapy with ACNU by hypertonic glucose in the BT4An rat glioma. AB - Hyperthermia increases the cytotoxicity of the nitrosourea BCNU (carmustine). Glucose given before treatment may further increase the value of thermochemotherapy, presumably by lowering tumour pH through blood flow reduction. The water-soluble ACNU (nimustine) is an alternative to other nitrosoureas in the treatment of gliomas. The drug is soluble without use of ethanol, and the eye complications when given intra-arterially are reduced compared with similar use of BCNU. The influence of simultaneous hyperthermia on treatment with ACNU, and the value of glucose administered before thermochemotherapy therefore were investigated in the malignant rat glioma BT4An. BD IX rats with subcutaneous BT4An tumours on the hind leg were treated with ACNU (i.p.), or ACNU and locally applied waterbath hyperthermia (44 degrees C for 45 min), with or without previous glucose (6 g/kg i.p. 2 hours before treatment). ACNU (10 or 20 mg/kg) alone and ACNU (20 mg/kg) after previous glucose did not influence tumour growth, compared to the controls. Simultaneous ACNU (10 mg/kg) and hyperthermia clearly was more effective than treatment with hyperthermia alone. Glucose load before treatment further enhanced the effect of combined ACNU and hyperthermia. Glucose before treatment did not change local toxicity or weight profiles of treatment with ACNU alone, or simultaneous ACNU and hyperthermia. Glucose load therefore represented a therapeutic gain when administered before thermochemotherapy with ACNU. PMID- 1895168 TI - Practitioners as educators. One solution to the CNM shortage. PMID- 1895169 TI - Birth setting for low-risk pregnancies. An analysis of the current literature. AB - This article reviews the literature on birth settings for women with low-risk pregnancies. Methodological issues of the existing research include nonrandom designs, small samples, selection differences, data limitation, and confounding bias. Studies for four birth sites are summarized: the home, freestanding birth centers, in-hospital birthing centers or birthing rooms, and traditional hospital settings. Despite the methodological limitations, nontraditional birth settings present advantages for low-risk women as compared with traditional hospital settings: lower costs for maternity care, and lower use of childbirth procedures, without significant differences in perinatal mortality. PMID- 1895167 TI - Chemotherapeutic treatment of extensive optic pathway tumors in infants. AB - Two infants, ages 14 and 4 months, with extensive optic pathway tumors were treated with intensive chemotherapy called MADDOC: nitrogen mustard, doxorubicin, cis-platinum, dacarbazine, vincristine, and cyclophosphamide. The first child had hydrocephalus with an enhancing mass at the hypothalamus which followed the optic radiation to include the lateral geniculate body and medial temporal lobe. A v-p shunt was placed, and biopsy revealed a Grade II astrocytoma. One month later, the child developed malignant ascites. Intensive induction chemotherapy was then begun with cis-platinum 100 mg/m2 and cyclophosphamide 3 g/m2 for two initial cycles. The ascites resolved within one week, and chemotherapy was continued for 10 courses of the 6-drug MADDOC regimen. CT scans showed a gradual shrinkage of the tumor mass by approximately 70%. The enhancing areas continued to decrease in size through 20 months after completing MADDOC. The child has not received radiation and is well 4 years 7 months post diagnosis. The second infant had massive enlargement of the right optic nerve with an enhancing chiasmatic mass extending into the suprasellar space, hypothalamus, and brain stem. This infant was not biopsied; she also received induction MADDOC chemotherapy for 12 cycles. CT scans showed a definite decrease in the chiasmatic mass by the fifth cycle, with continued reduction by approximately 40% after 10 months. Twenty-three months from diagnosis there was asymptomatic evidence of tumor growth. The child is being treated with carboplatinum and remains ophthalmologically and radiographically stable 43 months from diagnosis. PMID- 1895170 TI - Dynamic characteristics of the circumvaginal muscles during pregnancy and the postpartum. AB - Weakened circumvaginal muscles (CVM) may occur after childbirth and may be associated with obstetric factors such as perineal outcome, episiotomy, length of second stage labor, baby weight, and pushing technique. Pressures developed by the CVM during pregnancy and postpartum were obtained to test the hypothesis that significantly lower pressures would be developed by the CVM in the early postpartum than during pregnancy. The sample consisted of 29 pregnant women who planned to deliver at a birth center. A follow-up study was performed approximately one year after delivery to determine if improvement of the CVM occurred over time. The results supported the hypothesis and indicated that restitution of the CVM occurred after the early postpartum period. PMID- 1895171 TI - Caffeine and its effects on pregnancy and the neonate. AB - In animal studies, fetal loss, decreased fetal weight and size, and major skeletal defects have been reported when dosages of more than 80 mg/kg of caffeine were used. Human epidemiologic studies that examine the relationship between caffeine use and congenital abnormalities are not conclusive; however, there is some evidence to suggest a caffeine effect upon fetal growth patterns. Because caffeine drinking is so often associated with the use of other drugs such as tobacco, it is difficult to ascertain which drug has the effect on growth, or if it is a combined effect from both drugs. A tripling of the half-life of caffeine in the last two trimesters of pregnancy resulting in much higher caffeine blood levels for both mother and fetus, combined with the neonate's inability to metabolize caffeine, could account for the indications of neonatal caffeine withdrawal observed in the first week after birth. PMID- 1895172 TI - Behavioral interaction of fathers with infants and mothers in the immediate postpartum period. AB - This study describes paternal behaviors of first-time fathers with their partner and newborn immediately after birth and identifies a progression of behaviors with the infant within the first 15 minutes after birth. Videotapes were made of 24 first-time fathers observed at birth a traditional delivery room setting. Utilizing an ethological approach to define behavioral codes, episodes of paternal behavior were measured with time interval sampling. Using a modified frequency method, behaviors were identified in four main categories: proximity, gaze, touch, and movement. The analysis showed that proximity and gaze were high frequency behaviors and touch and movement were low-frequency behaviors. A progression of behaviors was identified, with gaze starting out high and diminishing, proximity and movement increasing over time, and touch remaining low but constant. Limitations of the setting and implications for clinical practice and research are discussed. PMID- 1895173 TI - Management of retained placenta using intraumbilical oxytocin injection. AB - Manual removal of the placenta carries significant risk of hemorrhage and infection plus the risks associated with general anesthesia, if used. Transporting the patient from home or birthing center to hospital or from birthing room to delivery room or operating room is also disruptive to the patient and the initial parent-infant attachment process. The injection of oxytocin into the umbilical vein is a safe procedure that can cause placental separation and delivery, thus preventing the need for manual removal for some women. This technique can be useful in a nurse-midwifery practice in the management of a retained placenta or prolonged third stage of labor. The following review of current research and example of a protocol used in a nurse midwifery service will provide guidance for incorporating this procedure into practice. As with any new technique, the need to continue to collect and publish outcome data is important. PMID- 1895174 TI - Prenatal screening for illegal drugs. Dilemma for the nurse-midwife. AB - Prenatal screening for illegal drugs poses very complex ethical problems for the nurse-midwife who must make the decision whether to screen for illegal drugs and whether to report positive results to state child abuse investigators. We argue that the results of prenatal screening for illegal drug use should not be used for determination of child abuse and that the nurse-midwife should not be required to report the results of these screens for illegal drugs to state child protection agencies. It is far from clear that required reporting offers any benefit to the fetus or future child, and there are serious ramifications of reporting for the fetus, the pregnant woman, and the nurse-midwifery profession. However, we do argue that prenatal screening for both illegal and legal drug use should be encouraged and should be done as early as possible in the pregnancy. Prenatal screening for drugs should only be used by the nurse-midwife as a diagnostic procedure wherein standard informed consent and confidentiality restraints are maintained. PMID- 1895175 TI - Nurse-midwifery in rural Pakistan. AB - Pakistan is a relatively new nation of predominantly Islamic influence. Like many developing countries, it is plagued by extensive communicable diseases, malnutrition, inadequate sewage systems, and illiteracy. Religious beliefs and cultural influences impact heavily on access to health care and on maternal-child health outcomes. This paper examines the major maternal-child health problems encountered, as well as implications for midwifery practice in an Islamic country. PMID- 1895177 TI - Minimum nursing data set. PMID- 1895176 TI - Cognitive skills & development competencies for conducting research critiques. AB - As the nursing profession expands its unique scientific body of knowledge, it is essential that all professional nurses become capable of evaluating the scientific and clinical merits of this information generated by nursing research. Three developmental levels of research critique skills are delineated by the nurse reader's competencies: novice, intermediate, and advanced. Each developmental level is described in relation to five cognitive skills which underlie the proposed competencies: knowledge, comprehension, analysis, evaluation, and synthesis. PMID- 1895178 TI - Survey of nursing research in NYS: XIII. PMID- 1895179 TI - Working smarter: the use of priorities and a model in designing nursing research. AB - It is imperative to maximize our limited resources conducting nursing research through targeting studies in priority areas and structuring projects to foster comprehensiveness and generalizability. This paper reviews priorities for nursing research and presents a model for research, detailing its component domains and the relationships among these domains. It further applies the model to a specific research project concerned with comparing the outcomes of two intensive community based service programs for children with serious emotional disturbances and discusses the implications of applying this model. PMID- 1895180 TI - Light up your practice with nursing research. AB - All nurses have a part to play in nursing research, even those with elementary skills in research. This article introduces nursing research to nurses in clinical practice who may not be familiar with the research process, but who can use research findings to guide their practice. It is also intended to foster collaboration between researchers and practitioners, so that they will work together through research to establish a specialized knowledge base for nursing. PMID- 1895181 TI - Ileocolic replacement of esophagus in children with esophageal stricture. AB - Between 1970 and 1988, 12 restrosternal esophageal substitutions using an ileocolic interposition were performed. The ages of the 12 children ranged from 2 to 6 years. In 11 children the esophageal strictures were secondary to ingestion of caustic liquid. All patients had failed esophageal dilation therapy. One death occurred on the 7th postoperative day following an episode of cardiac arrest at surgery. Early postoperative complications included three cervical ileoesophageal anastomotic leaks, which healed spontaneously. One patient had gastrointestinal bleeding 10 years postoperatively. This was controlled by antacid therapy without recurrence. Redundancy of the interpositioned ileocolic segment was observed in three children. All 11 surviving patients can eat a normal diet and have normal growth and development. PMID- 1895182 TI - The use of omental pedicle flap for tracheobronchial reconstruction in infants and children. AB - For the surgical repair of long-segment tracheal stenosis, costal cartilage graft or extensive resection with end-to-end anastomosis has often been used. Both procedures have a risk of developing anastomotic leakage, which is potentially a lethal complication, or stenosis resulting from compromised blood supply to the tissue at the anastomosis. We have used omental pedicle flap (OPF) to seal the anastomotic line and to restore the vascularity of the graft and the trachea in an attempt to avoid fatal complications. During the period between 1986 and 1990, OPF technique was used in tracheobronchial reconstruction in six patients aged 4 months to 3 years; cartilage graft for extensive tracheal stenosis (4), tracheal resection and anastomosis (1), and bronchial resection and anastomosis (1). The omentum was separated from the colon to form an OPF with the right gastroepiploic vessels preserved. The OPF was brought to the upper trachea in the mediastinum through the retrosternal space. There was no immediate postoperative death due to anastomotic leak. Endotrachial tubes were removed in all patients. Four of the six are totally free of airway problems. One patient showed persistent stridor because of remaining stenosis at the cervical trachea. The remaining one patient who underwent bronchial resection developed anastomotic stenosis probably due to the compression of the floppy left main bronchus by adjacent aorta. The OPF seems to be an important surgical adjunct in order to eliminate fatal complications in tracheobronchial reconstruction. PMID- 1895183 TI - Anatomical reconstruction of the thyroglossal duct. AB - The high postoperative recurrence rate of the thyroglossal duct cyst is well known. Since Sistrunk's operation was used, the recurrence rate was remarkably reduced, but the anatomical description of the thyroglossal duct through the entire tract has not been clarified in detail. For a more accurate anatomical understanding of the thyroglossal duct, 10 specimens obtained from Sistrunk's operation were studied using histological reconstruction, and a common running pattern of the thyroglossal duct was found. The cyst is usually located caudal to the hyoid bone mostly at the midline. The duct extends upward from the cyst ventral to the hyoid bone, with many or a few branches and secretory glands. These ducts or branches merge into a single duct at the level of the cranial portion of the hyoid bone. However, as it leaves the hyoid bone and approaches the foramen cecum, a single duct spreads out into many ductuli like the tip of a broom, which communicate with many secretory glands. There were three cases in which the duct was found behind the hyoid bone, but in no case did the thyroglossal duct run through the back of the hyoid bone. The duct behind the hyoid bone was recognized as a branch from the main duct in the dorsal direction. It ascended to the dorsal surface of the hyoid bone and terminated blind. These findings emphasized the importance of Sistrunk's operation to prevent a recurrence. PMID- 1895184 TI - Histological classification of nesidioblastosis: efficacy of immunohistochemical study of neuron-specific enolase. AB - Pancreatic specimens of six patients with nesidioblastosis were studied by light microscopy and immunohistochemistry in order to classify the changes of the endocrine pancreas and relate them to the clinical outcome. Neuron-specific enolase immunostaining was useful in demonstrating the distribution of whole pancreatic endocrine cells. The six cases with nesidioblastosis were classified into two types; four cases of focal type (head 1, body 1, tail 2), and two cases of diffuse type. The histological classification show a correlation to the clinical outcome. The patients with a focal body or tail type showed normal blood sugar levels immediately after operation. On the other hand the patients with both diffuse type and a focal head type needed medical treatment within a few months after operation. Therefore, these cases should be followed with great care postoperatively. A partial 80% to 90% pancreatectomy might be sufficient for each type except for the focal head type. When the intraoperative examination (both macroscopic and microscopic) is suggestive of focal head type, a pancreatectomy of 95% or more is called for. PMID- 1895185 TI - The isolated bowel segment (Iowa model II) created in functioning bowel. AB - In experimental rats (n = 15), an isolated bowel segment (IBS) was created by (1) initial enteropexy between an 8-cm-long jejunal segment and the liver margin (hepatoenteropexy; Iowa model II) with its proximal and distal ends divided and immediately reanastomosed in an end-to-end fashion to reconstruct the bowel; and (2) secondary division of the IBS mesentery 5 weeks later. The IBS is then completely free of its mesentric and intramural nervous and vascular communications. The viability of the IBS is preserved by vascular collaterals developed at the hepatoenteropexy. Twelve rats proceeded to the second procedure, having tolerated regular rat chow with satisfactory weight gain. The Iowa model II created in functioning bowel was evaluated by contrast studies and myoelectrical activities. Contrast studies demonstrated peristalsis in the IBS. In the myoelectrical recordings, the frequency of slow wave was 32.5 +/- 1.0 in the IBS and 36.3 +/- 0.8 in the normal bowel (P less than .05). During fasting, the migrating motor complex (MMC) was observed to propagate aborally in the IBS in a coordinated fashion. The cyclic period of the MMC was 17.2 +/- 1.1 minutes in the IBS and 15.8 +/- 0.8 minutes in the normal bowel (P = .30). We conclude from this study that (1) the IBS (Iowa model II) retains motor function as demonstrated by successful feeding, as well as contrast studies and myoelectrical recordings that were essentially identical to those in the normal bowel; and (2) the IBS (Iowa model II) has significant research potential for studies of bowel physiology. PMID- 1895186 TI - The impact of extracorporeal membrane support in the treatment of congenital diaphragmatic hernia. AB - Neonates with congenital diaphragmatic hernia (CDH) treated by immediate surgical intervention and conventional ventilatory support have an overall poor survival. The potential of extracorporeal membrane oxygenation (ECMO) therapy to improve survival of infants with CDH remains controversial. Comparison was made in a single institution's pre-ECMO and post-ECMO survival statistics to establish efficacy of extracorporeal support for persistent pulmonary hypertension (PPH). This study was accomplished by stratifying patients by an oxygen index (OI). Sixty-eight patients were treated for CDH from 1977 to 1986 without ECMO. Fifty eight patients underwent repair of CDH within the first 24 hours of life. Data could be retrieved for calculation of the OI in 46 patients. Nineteen patients developed an OI of 40 or greater; one survived (5%). Three of 27 patients with an OI less than 40 died (OIs = 34, 38, and 38). Thirty-one patients were treated from 1987 to 1989 and none were excluded from ECMO based on a minimum PO2. Fifteen had an OI less than 40 (range, 1 to 38), were treated conventionally, and 13 survived (87%). Sixteen patients had an OI greater than 40 and 13 qualified for ECMO. Nine of 13 survived (69%). Comparing pre-ECMO and post-ECMO survival for infants with an OI of 40 or greater (5% v 69%), there is a significant improvement in survival when ECMO is used (P less than .001). ECMO support offers a strong adjunct in management of neonates with CDH who develop PPH. PMID- 1895189 TI - Debridement of periumbilical necrotizing fasciitis: importance of excision of the umbilical vessels and urachal remnant. AB - The operation of a neonate with periumbilical necrotizing fasciitis consisted of (1) excision of infected skin, fat, and fascia (including the umbilicus); (2) a limited laparotomy, with ligation and excision of the umbilical vessels and urachal remnant; and (3) placement of a temporary silastic patch over the central abdominal defect. Pathological sections confirmed the spread of infection along the vessels and urachal remnant. Excision of the vessels and urachal remnant may be crucial to survival from periumbilical necrotizing fasciitis. PMID- 1895188 TI - Effectiveness of an intussusceptive antireflux valve to prevent ascending cholangitis after hepatic portojejunostomy in biliary atresia. AB - An intussusceptive antireflux valve was created in the Roux-en-Y loop at the same time as the hepatic portojejunostomy (Kasai procedure) for the purpose of preventing ascending cholangitis in 14 new cases of biliary atresia and in 6 long term survivors of the Kasai operation after episodes of ascending cholangitis. Ascending cholangitis did not develop in any of the 13 new patients who showed bile outflow following a modified Kasai procedure with antireflux valve nor in 5 of 6 patients who had secondary valve implementation. Postmortem examination of a patient with a valve who died 2 years 3 months after surgery showed that the structure of the valve was intact and that the valve still was quite effective as an antireflux mechanism. PMID- 1895187 TI - Carotid artery reconstruction following neonatal extracorporeal membrane oxygenation. AB - Although reconstruction of the right common carotid artery (RCCA) in neonatal extracorporeal membrane oxygenation (ECMO) patients is intuitively attractive, there is little known about prolonged arterial cannulation and how it may affect subsequent vascular repair. A histological study of RCCA segments from neonatal ECMO patients was performed, so that cannulation technique and catheter design could be optimized before proceeding with arterial reconstruction. Circumferential transmural necrosis (CTN) was found in 25 of 31 (80%) arteriotomy specimens in comparison with 2 of 9 (20%) more proximal carotid specimens; the remaining specimens in each group demonstrated either focal subintimal or focal transmural necrosis. CTN was more common in patients with longer ECMO runs (96 +/ 5.9 versus 75 +/- 5.6 hours, P = .009; arteriotomy site), but was independent of cannula size, birthweight, and gestational age. Eleven patients have undergone RCCA reconstruction. Doppler flow studies at 4 to 7 months of follow-up in five patients demonstrated slightly higher right-sided versus left-sided peak systolic, end-diastolic, and mean flow velocities. No neurological or developmental problems could be attributed to vascular reconstruction. In conclusion, RCCA reconstruction is technically feasible, but due to the high prevalence of CTN at the arteriotomy site, excision of this segment is recommended at the time of arterial repair. PMID- 1895190 TI - Double atresia of the hindgut. AB - An unusual case of double atresia of the rectum, including an imperforate anus is reported. The author was unable to find a similar case published before. PMID- 1895191 TI - Surgical management of ambiguous genitalia in the infant and child. AB - Proper gender assignment to a neonate born with ambiguous genitalia is a social emergency of the newborn period. Once an appropriate sex assignment has been made, the next critical step is performance, if needed, of a reconstructive procedure in a timely fashion. In an attempt to evaluate our experience with this unique group of patients, we have retrospectively reviewed the course of 69 children with ambiguous genitalia managed surgically at this institution between 1974 and 1989. This series consists of 32 genotypic females with congenital adrenal hyperplasia (CAH), 10 children with mixed gonadal dysgenesis (MGD), 10 male pseudohermaphrodites, 3 true hermaphrodites, 8 genotypic females with urogenital sinus anomalies (UGS), and 6 genotypic males with bilateral undescended testes and penoscrotal hypospadius. All newborns initially seen at this institution received proper sex assignment within the first week of life. Prior to 1980, 17 of the children with CAH underwent clitorectomy and vaginoplasty and three underwent clitoral recession and vaginoplasty. After 1980, 10 patients with CAH were managed with clitoral recession and vaginoplasty and 2 with vaginoplasty alone. Eight of 10 cases of MGD were given a female sex assignment and all 8 underwent gonadectomy due to the high risk of gonadoblastoma; the other 2 children were raised as males. There were 3 true hermaphrodites of which 2 were assigned female gender roles and were managed with a clitoral recession and vaginoplasty. All 10 male pseudohermaphrodites were raised as females and all underwent bilateral orchidectomy. The 8 children with UGS were raised as females and underwent vaginal reconstruction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1895192 TI - Differences in mortality from thermal injury between pediatric and adult patients. AB - Children differ from adults in their responses to thermal injury, as reflected by higher reported mortality rates for equivalent major injuries. The age at which children's survival rates equal those of young adults has not been well defined, and some investigators have recently claimed that pediatric and adult burn mortality do not differ. We evaluated age-related mortality among 1,443 consecutive patients without inhalation injury treated from 1978 to 1988, inclusively. The sample consisted of 595 children aged 12 years or less, 243 children aged 13 to 20 years, and 605 young adults aged 21 to 40 years who served as a comparison group of patients with the best predicted survival. We separately examined mortality in patients with burns exceeding 30% total body surface area. There were no significant differences in mortality between age groups for the study sample as a whole, but among patients with large burns, children aged 0 to 48 months had higher mortality than comparably injured adults (31% v 12%, P less than .05 by analysis of covariance). Improvements in survival were also demonstrated between the first and second halves of the study period for children aged 25 months to 8 years. These data indicate that children 48 months of age and younger do not tolerate large thermal injuries as well as adults. Improvements in pediatric burn survival are being achieved in most age groups. PMID- 1895193 TI - Primary obstructive megaureter. AB - Twenty-three children with primary obstructive megaureters presented between 1978 and 1988 to the Princess Margaret Hospital for Children in Perth. Twenty-eight ureters were treated. Urinary infections were the presenting feature in 14 children. The obstructive segment was transvesically excised. Histopathologic examination of the distal, intramural ureter showed fibromuscular disarray with a relative increase in fibrous tissue and reduction of musculature in all specimens. Twenty-two ureters were tapered by excision and all 28 were reimplanted using an antireflux technique. Seventeen children were followed for an average of 3 years. Seven children showed renal growth, reduction in ureteric size by greater than 2 cm, improvement in glomerular filtration rate by more than 10%, no obstruction on reflux, and no infections in postoperative period. Four children showed all the above but suffered one or more infections after the operation. Of the remaining 6 children, 3 had postoperative obstruction and 3 had vesicoureteric reflux. PMID- 1895194 TI - Flow cytometric DNA analysis of neuroblastoma: prognostic significance of DNA ploidy in unfavorable group. AB - Flow cytometric DNA content analyses were performed on samples of 54 patients with neuroblastoma. DNA aneuploidy was detected in 55.6% of the 54 patients. A high incidence of DNA aneuploidy was observed in patients with prognostically favorable variables such as age (less than 1 year), clinical stage (I, II, or IVs), and primary site (extraadrenal sites). DNA aneuploidy was predominant in surviving patients, even in those with unfavorable variables. In patients 1 year old or more, the survival rate among those with DNA aneuploidy was 58.8% compared with 28.6% in patients with diploidy. Likewise, in patients with advanced stage (III or IV) neuroblastoma, the survival rate among those with DNA aneuploidy was 63.2% compared with 30.4% in patients with DNA diploidy. It is concluded that DNA content analysis is of value in predicting the prognosis of patients with neuroblastoma. PMID- 1895195 TI - Immunohistochemical analysis of N-myc protein expression in neuroblastoma: correlation with prognosis of patients. AB - We have analyzed N-myc gene amplification and N-myc protein expression in 41 primary neuroblastomas. In this series, 22 patients are currently alive and disease-free, whereas 19 patients have died or are alive with progressive disease. All tumor samples were obtained at operation. N-myc gene amplification was detected by Southern blot analysis, and N-myc protein expression was detected using Bouin-fixed, paraffin-embedded tissue sections and immunohistochemical staining with anti-N-myc gene products serum. N-myc protein expression was detected in all 9 tumors with N-myc gene amplification (greater than or equal to 10 N-myc gene copies). Among 19 patients with poor prognosis, N-myc gene amplification was detected in 8 (42%) and N-myc protein expression in 18 (95%); neither was detected in 20 of the 22 patients who survived free of disease. We conclude that the immunohistochemical detection of N-myc protein expression is one of the most unfavorable prognostic factors in neuroblastoma patients. PMID- 1895196 TI - Hemorrhage into mesenteric cyst following trauma as a cause of acute abdomen. AB - Intraabdominal lymphangiomas are rare. Most cases are asymptomatic, except when complicated. This is a case report of a 8-year-old boy with hemorrhage into a mesenteric lymphangioma following trauma, as a cause of acute abdomen. Prompt diagnosis and operation were imperative in the proper management of this child. PMID- 1895197 TI - Treatment of Hirschsprung's disease with a modified Duhamel-Grob-Martin operation. AB - Since 1965 we have treated Hirschsprung's disease with a modified Duhamel-Grob Martin operation. During this time, there have been many changes in principles of treatments and the operative technique has been reinforced. It will be divided into three different periods. From 1965 to 1980, 202 cases of Hirschsprung's disease were treated with a modified Duhamel-Grob-Martin procedure. This method had several advantages--minimum complications; good fecal control and continence; and no enlargement of the remaining colon--but anastomotic leakage and local infection were the main disadvantages. Since 1980 the operation technique has been reinforced in several points: complete preoperative colon preparation; selection of suture materials; and gentle, meticulous, and accurate surgical technique. Forty-six more patients were treated. No anastomotic leakage and local infection were experienced in this group. From April 1984 to January 1990, all patients with Hirschsprung's disease received the pull-through procedure without the colostomy even in the neonates. Eighteen infants less than 2 months of age have been treated. All patients survived the operation without any significant complications. PMID- 1895198 TI - Ontogeny of fetal sheep polymorphonuclear leukocyte phagocytosis. AB - Premature infants and neonates are vulnerable to bacterial sepsis. This susceptibility may be due to the relative immaturity of their immune systems. To determine if neonates and, in particular, premature infants have decreased polymorphonuclear leukocyte (PMN) phagocytosis, we tested PMN phagocytosis of Staphylococcus aureus as a function of gestational age in the fetal lamb model. Because phagocytosis is made more efficient by the presence of opsonins in plasma, fetal and postnatal PMN phagocytosis were also measured after exposure to fetal and adult plasma. PMNs were isolated from fetal lambs at 104, 114, 124, and 141 days' gestation (term gestation for the fetal lamb is 145 days), as well as from 10-day-old neonatal sheep and adult sheep. Labeled S aureus were opsonized by incubation in either fetal or adult plasma, or left unopsonized for baseline values. Phagocytosis was measured as a percent of adult PMN phagocytosis after adult plasma opsonization. It was found that fetal PMN function is limited by two factors during the early third trimester: a primary defect in the ability of the PMN to phagocytose S aureus despite adequate opsonization, and the diminished ability of autologous fetal plasma to opsonize bacteria. The defect in PMN phagocytosis disappears late in the third trimester, but the inability of the fetal plasma to opsonize effectively continues until after birth. PMID- 1895199 TI - The posterior sagittal approach for reconstruction of severe rectovaginal injuries. AB - Reconstruction of major perineal lacerations in the small child is difficult and frequently results in less-than-satisfactory continence. A 2 1/2-year-old girl who had sustained a fourth-degree perineal laceration at 9 months of age presented with a common rectovaginal orifice and complete fecal incontinence. Repair was carried out via a posterior sagittal approach, resulting in a normal appearing perineum with complete continence. The techniques used in the posterior sagittal approach allow precise identification of the striated muscle complex and, therefore, offer a valuable means of achieving complete continence. Although the technique was originally described for reconstruction of congenital anomalies, this report demonstrates it to also be useful for reconstruction of severe perineal trauma. PMID- 1895200 TI - Caudal migration of the verumontanum. AB - The location anomaly of the verumontanum has not been described in the literature. We confirmed that the verumontanum was located either in the sphincteric or bulbous urethra in 61 of 477 patients with hypospadias (12.8%) through endoscopic examination and urethorgraphy. There was a patient with bilateral cryptorchidism who had distal location of the verumontanum. The patients with hypospadias and caudal migration of the verumontanum showed significantly low response of testosterone to human chorionic gonadotropin stimulation compared with normal controls. The incidence of caudal migration of the verumontanum was higher in the patients with a severe degree of hypospadias than in those with mild hypospadias. These results suggest that distal location of the verumontanum may be the result of an insufficient action of androgens during the period of critical sexual differentiation in the male embryo. We call this phenomenon caudal migration of the verumontanum, which seems to be a new clinical entity. PMID- 1895201 TI - [Reaction and interactions of drugs]. PMID- 1895202 TI - [Molecular modelling of usambarensine, tubulosine and emetine, cytotoxic amebicide alkaloids]. AB - The analyses of the different possible conformations of usambarensine, tubulosine and emetine, which possess interesting cytotoxic and amoebicide properties showed us that they cannot take the planar conformation proposed to explain the activity of this type of molecules on protein synthesis. Nevertheless, a common (non planar) conformation exists where the angles between the two plans containing the aromatic rings are nearly the same for the three compounds. This fact could confirm the hypothesis of a common receptor which would be slightly different in amoebae because of its higher sensitivity to usambarensine. PMID- 1895203 TI - Transplacental antiretroviral therapy with 9-(2-phosphonylmethoxyethyl)adenine is embryotoxic in transgenic mice. AB - Transgenic Mov-14 mice, which carry the provirus of Moloney murine leukemia virus (Mo-MuLV) in the germ line and begin to produce infectious virus on embryonic day 14, were used to evaluate the ability of 9-(2-phosphonylmethoxyethyl)adenine (PMEA) to cross the placenta and protect embryos from viremia. We have used the Mov-14 model previously to demonstrate the antiviral efficacy and lack of teratogenicity of transplacental therapy with 3'-azido-3'-deoxythymidine (zidovudine, ZDV). PMEA was administered to pregnant females by daily intraperitoneal injection or by osmotic pump. In contrast to ZDV, PMEA was either noneffective in preventing viremia in the offspring or embryotoxic, depending on the dose. The specific toxic effects seen were resorption of pregnancy, low birth weight, and neonatal death. Histopathological analysis of neonatal mice exposed to PMEA showed severe lymphoid depletion of the thymus. We conclude that PMEA therapy is contraindicated for use during pregnancy. PMID- 1895204 TI - Cryotherapy for cutaneous Kaposi's sarcoma (KS) associated with acquired immune deficiency syndrome (AIDS): a phase II trial. AB - To assess the response and toxicity of liquid nitrogen cryotherapy for cutaneous lesions of Kaposi's sarcoma (KS) associated with AIDS, we evaluated 20 subjects with biopsy-proven KS in a phase II clinical trial. Subjects had two to four cutaneous KS indicator lesions treated with liquid nitrogen cyrotherapy. Treatment was repeated at 3 week intervals, allowing adequate healing time. On average, subjects received three treatments per lesion with a mean follow-up time of 11 weeks (range of 6-25 weeks). One treatment consisted of two freeze-thaw cycles, with thaw times ranging from 11 to 60 s per cycle. A complete response was observed in 80% of treated KS lesions and lasted a minimum of 6 weeks following the completion of therapy. Greater than 50% cosmetic improvement of KS was observed. Histopathology of treated lesions correlated poorly with cosmetic improvement. Response was not predicted by tolerance to zidovudine therapy, CD4+ cell count, presence of B symptoms, or previous chemotherapy. Subjects without prior history of opportunistic infection (OI) were more likely to have a better response than those with a prior history of OI. Subjects tolerated cryotherapy well. Blistering occurred frequently, but local pain was limited and relieved by acetaminophen. Secondary infection did not occur. Based on this study, we recommend cryotherapy to subjects with cutaneous KS lesions. Liquid nitrogen cryotherapy is easily applied as a primary therapy, and may also have a role in the treatment of cutaneous KS lesions that respond slowly or show incomplete cosmetic improvement with systemic therapies. PMID- 1895205 TI - Intensity of in-hospital care for persons with AIDS. AB - We evaluated the intensity of medical care for 30 consecutive AIDS patients at one hospital, using methodology based on the Delay Tool of Selker et al. Of 25 AIDS patients who survived hospitalization, 15 had at least one delay day in the hospital. Major factors associated with care that could have been provided at an alternative site included difficulty with skilled nursing facility placement in 20% of the patients, difficulty coordinating out-of-hospital care in 28%, and scheduling of outpatient surgical procedures in 12%. For the 15 patients who could have received some of their care at a lower intensity setting, a median of 7 hospital days could have been potentially saved with better coordination of outpatient care and increased availability of skilled nursing facilities. The five patients who died in hospital also used large amounts of resources and had long lengths of stay. Prior studies of non-AIDS patients revealed similar results, suggesting that, for reasons of quality of care, quality of life, and economics, policy-makers must develop managed care programs, skilled nursing facilities that accept AIDS patients, inpatient psychiatry facilities, and increased hospice availability. PMID- 1895206 TI - High-titer positive nontreponemal tests with negative specific treponemal serology in patients with HIV infection and/or intravenous substance use. AB - Nontreponemal testing is a valuable tool in screening for syphilis. False positive reactions are uncommon and are usually at a titer less than 1:8. We describe eight intravenous substance abusers and/or HIV-positive patients with high-titer (greater than or equal to 1:16) nontreponemal and negative treponemal serologies in whom the diagnosis of syphilis is unproven and possibly false. PMID- 1895207 TI - Canadian multicenter azidothymidine trial: AZT pharmacokinetics. AB - The study objective was to describe the pharmacokinetics of azidothymidine (AZT) in a large population of early, asymptomatic human immunodeficiency virus (HIV) infected individuals. The study design was a multicenter, prospective, descriptive single-dose pharmacokinetic study. Each of 66 fasting, male, HIV infected homosexuals older than 18 years of age and in CDC classifications II, III, and IVC2 received a single 400-mg oral dose of AZT with subsequent pharmacokinetic measurements performed during an 8-h period for AZT and its major metabolite, glucuronylazidothymidine (GAZT). Results were obtained in 65 patients (36 smokers, 29 nonsmokers), of whom 3 were noted to have hepatic dysfunction. In those with normal hepatic function, the following parameters were described: AZT, area under the curve (AUC) +/- SD, 9.9 +/- 5.7 microM.h, maximum concentration (Cmax) +/- SD, 7.3 +/- 4.7 microM; time to maximum concentration (Tmax) +/- SD, 0.93 +/- 0.42 h, and half-life (t1/2) +/- SD, 1.0 +/- 0.8 h. Corresponding values for GAZT were: AUC +/- SD 35.7 +/- 10.3 microM.h, Cmax +/- SD 21.3 +/- 7.3 microM, Tmax +/- SD 1.2 +/- 0.50 h, t1/2 +/- SD 0.98 +/- 0.62 h, No significant differences were found in comparisons of study site, CDC classification of disease, smokers versus nonsmokers, and in patients with hepatic dysfunction, although a higher AUC and earlier Cmax for AZT was noted in the latter group. It is concluded that AZT pharmacokinetics are similar in patients with early asymptomatic HIV disease when compared with previous reports in patients with later disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1895208 TI - Relationship and prognostic value of endogenous interferon-alpha, beta 2 microglobulin, and neopterin serum levels in patients with Kaposi sarcoma and AIDS. AB - We investigated whether elevated serum levels of beta 2-microglobulin and neopterin were related to the abnormal in vivo production of interferon described in patients with human immunodeficiency virus (HIV) infection, and whether these factors might add to measurements of CD4+ T cells in predicting survival and tumor regression in patients with Kaposi sarcoma associated with AIDS. beta 2 Microglobulin and neopterin levels were strongly correlated (r = 0.82), and were each significantly higher in patients with detectable serum interferon-alpha activity. Inverse correlations were observed between prognosis and levels of these serum products. Prediction by CD4+ T-cell count of tumor regression after treatment with interferon-alpha and zidovudine was improved by each of two factors: (a) the presence or absence of endogenous interferon-alpha activity, and (b) a combined variable reflecting relative levels of the interferon-inducible products, beta 2-microglobulin and neopterin. The level of beta 2-microglobulin was the single best predictor of survival. When beta 2-microglobulin was not considered, the endogenous interferon-alpha variable was the best predictor of survival, and the prediction was enhanced by addition of the combined variable, or the neopterin value alone. We conclude that serologic markers, which directly or indirectly reflect activation of the endogenous interferon system, may be valuable adjuncts to CD4+ T-cell counts in assessing prognosis and selecting and evaluating treatments for patients with Kaposi sarcoma and AIDS. PMID- 1895209 TI - Populations at increased risk of HIV infection: current knowledge and limitations. AB - Research data describing the prevalence and patterns of behaviors that place persons at increased risk of HIV infection are extremely limited. The scarcity of data has constrained potential applications of surveillance data, research on specific high-risk behaviors, and epidemiological studies. This article critically reviews available research for four population groups: intravenous drug users, homosexual males, and sexually active adolescents and adults. The fallacies inherent in estimating risk group size underscore the need for population-based research that can provide detailed data on sexual and drug use behaviors. PMID- 1895210 TI - HIV prevention among injecting drug users: three years of experience from a syringe exchange program in Sweden. AB - Exchange of syringes and needles has for the last 3 years been offered to injecting drug users as part of an HIV prevention project in a small university town in south Sweden. The program at the local hospital has been visited by 979 drug users, of which 182 have participated on a more regular basis. The typical participant is a 30-year-old male who has injected amphetamine or heroin for at least 10 years. The seroprevalence for HIV among drug users in south Sweden has been maintained at approximately 1% in contrast to up to 60% in subpopulations from other Scandinavian regions with a comparable drug problem. No project participant has become HIV infected during the study period and a reduction in risk behavior has been noted among local drug injectors. The HIV prevention project has attracted many individuals with no previous contact with drug rehabilitation programs; for a number of drug users, the syringe exchange has served as an introduction to such treatment efforts. PMID- 1895211 TI - Changes in sexual practices over 5 years of follow-up among heterosexual men in San Francisco. AB - This report describes changes in sexual behavior of 209 heterosexual men enrolled in a prospective study since 1984. Data were analyzed separately for men who married during the 60 months of follow-up. Study subjects reported fewer total sexual partners and an increase in condom use in the more recent time periods compared to the first period. The proportion of never married men reporting two or more partners in the previous 6 months decreased from 53.2 to 40.7%. All of these men were human immunodeficiency virus seronegative on entry and only one documented seroconversion occurred during the follow-up. PMID- 1895212 TI - Seroprevalence of HTLV-I/II and HIV-1 infection among male intravenous drug abusers in Chicago. AB - We surveyed for serologic evidence of either HIV-1 or HTLV-I/II infection in 387 male veterans who entered into an inpatient drug treatment center. Serum was obtained after receiving written informed consent. Serum specimens were tested by enzyme-linked immunosorbent assay for antibody to HIV-1 and for antibody to HTLV I/II; sera that were repeatedly reactive were then tested by Western blot (HIV 1/HTLV-I/II) and radioimmunoprecipitation assay (HTLV-I/II). Sixty-five of 387 (16.79%) patients were tested and confirmed as positive for HTLV-I/II only antibodies and 30 of the 387 (7.75%) were positive for HIV-1 only antibodies. An additional nine patients (2.32%) were seropositive for antibodies to both viruses. A statistically significant difference in the CD4/CD8 lymphocyte ratio was associated with HIV-1 seropositivity. HTLV-I/II seropositivity was strongly associated with black race, age, and duration of i.v. drug use, but not with sexual intercourse as determined by lifetime history of number of sexual partners, incidence of sexually transmitted diseases, type of drug used, or needle-sharing practices. PMID- 1895213 TI - Factors that could influence the spread of AIDS in Ghana, West Africa: knowledge of AIDS, sexual behavior, prostitution, and traditional medical practices. AB - Ghana is a West African nation in the early stages of the human immunodeficiency virus (HIV) epidemic. In a series of surveys done between 1987 and 1989, we examined factors related to the spread of HIV infection, including knowledge about the acquired immune deficiency syndrome (AIDS), sexual habits, use of prostitutes, traditional healer practices, and skin-piercing customs. Although a polygamous society, three-fourths of married men had only one wife. The number of sexual partners at any one time was generally low. However, the divorce rate was more than 29% and 55% of married men had current sexual partners in addition to their wives. Knowledge about AIDS was widespread, yet 4% of men interviewed had had a sexual encounter with a prostitute within the last month. Use of condoms was very limited and 66% of customers of high-class prostitutes refused to use a condom even after a request to do so by the prostitute. Skin piercing, including scarification, was done by an unsterile instrument by 39% of 74 rural traditional healers, many of whom had more than one patient per day. To combat the spread of AIDS, Ghanaians will have to apply their knowledge of AIDS risk factors to their actual behavior. Many of the social customs are products of poverty and its ensuing social consequences. Funds are needed for specific AIDS prevention programs as well as improved education and health care throughout the country. PMID- 1895214 TI - Behaviour change and stabilization of seroprevalence levels in communities of injecting drug users: correlation or causation? PMID- 1895215 TI - Soluble CD4 and dextran sulfate mediate release of gp120 from HIV-1: implications for clinical trials. PMID- 1895217 TI - Reduction of corneal astigmatism at cataract surgery. AB - We studied the effect at three months of four transverse astigmatic keratotomy incisions (TAK) performed prior to phacoemulsification in 61 eyes on corneal astigmatism. The optical zone was varied in each case depending upon the magnitude of preoperative astigmatism. The eyes were compared to 105 control eyes in which no astigmatic incisions were performed to assess the estimated effect of the TAK incisions. Keratometry readings were taken preoperatively and three months postoperatively. Surgically induced astigmatism was measured using vector corrected astigmatism. Improvement in astigmatism was reported in all three optical zone groups, but the astigmatism was undercorrected in each. No complications affecting vision were reported, indicating that TAK may be a safe way to reduce postoperative astigmatism when combined with phacoemulsification. PMID- 1895218 TI - Routine use of a lateral approach to cataract extraction to achieve rapid and sustained stabilization of postoperative astigmatism. AB - After observing that lateral under-riding scleral pocket incisions and closures decayed very little and required full correction on the table to achieve the desired reduction in astigmatism, I began performing routine lateral approaches to planned extracapsular cataract extraction (ECCE). The result was an improvement in early and prolonged stabilization of keratometric astigmatism. This improvement was statistically significant when compared with the identical surgery performed in the vertical meridian. Using a 6.5 mm scleral pocket incision and the same suture material and closure technique, I found that the results of phacoemulsification via vertical and lateral approaches were not statistically different from the planned ECCE via lateral approach. Scleral pocket incisions and modified shoelace closures with 11-0 polyester suture were used in all cases; no suture removal was performed. The early visual recovery with planned ECCE via lateral approach was equivalent to that with phacoemulsification but did not require the expensive instrumentation or the "phaco learning curve." The minimal and stable postoperative astigmatism, along with early and sustained visual recovery possible with ECCE via lateral approach, may reduce the potential benefit of mini-incision and foldable intraocular lens surgery. PMID- 1895216 TI - Intraocular lenses for small incision surgery. PMID- 1895219 TI - Myopic keratomileusis in situ: a preliminary report. AB - We describe a technique and report a retrospective evaluation of myopic keratomileusis in situ. Surgery was performed on 32 eyes, with a mean follow-up time of 128.7 days (range 90 to 194 days). The average reduction of myopia was 8.48 diopters (D) when measured by refraction and 3.96 D by keratometry (minor axis). A statistically significant Pearson correlation coefficient of 0.49 (P = .01) was found between these two variables. Postoperative mean manifest spherical equivalent was -1.70 D (standard deviation 2.54 D). Mean cylinder correction increased -0.48 D (range -2.25 to 2.00 D). Uncorrected visual acuity improved after surgery in all eyes, but in 14 eyes the best corrected visual acuity diminished. Multiple regression model disclosed a limited predictability of the technique. Complications included diminution of best corrected visual acuity, under- and overcorrections, increase in keratometric astigmatism and cylinder correction, keratitis, delayed corneal epithelialization, interface amorphous deposits, monocular diplopia, interface epithelialization, and opacification. The most frustrating was an elusive postoperative cycloplegic refraction. In our hands, myopic keratomileusis in situ was not a technically safe, precise, and predictable technique for correction of myopia. Further improvement in the technique and equipment may provide better results. PMID- 1895220 TI - Tissue addition theory of radial keratotomy: a geometric model. AB - We examined the use of a geometric model to explain the effects of radial keratotomy (RK) on corneal topography based on wound gape of radial incisions. Histopathologic studies of healed human RK incisions revealed incision gape in Bowman's membrane and anterior stroma, with intervening epithelial ingrowth or fibrous scarring. For six human RK incisions examined centrally, mid peripherally, and peripherally, the linear separation of the cut ends of Bowman's membrane averaged 0.012 mm, 0.018 mm, and 0.027 mm, respectively. The effect of postoperative corneal flattening of the "addition of tissue" within incisions was mathematically predicted by calculating the effects of inducing radial gape on a spherical shell. The predicted change in corneal curvature agreed closely with data from a human case report. The "tissue addition" theory may partly explain the change in corneal topography following RK and subsequent wound healing. PMID- 1895221 TI - Kriss cuts for the correction of high myopia. AB - We describe a radial keratotomy technique for the correction of high myopia. At present, the highest myopic correction is obtained by the smallest optical zone diameter (3 mm), by the maximum number of incisions (16), by the maximum number of redeepenings (3), and by incision of the tissue bridges. To obtain additional corneal flattening, we suggest lengthening the incisions curvilinearly. We present results of cases treated with curvilinear incision and two other techniques. PMID- 1895222 TI - Corneal epithelium following intraepikeratophakia. AB - The corneal epithelium in eight patients was surveyed by biomicroscopy and specular microscopy before and after the intraepikeratophakia procedure. Autografting of the epithelium was also examined by electron microscopy. Although the superficial layer of the epithelium was damaged, the wing cell layer remained intact, contributing to the epithelialization of the cornea. Epithelialization of the cornea after surgery was completed in three days in all cases. The epithelium was stained with fluorescein, revealing abnormalities in the superficial layer. This stained superficial epithelium was replaced with new epithelium within seven days, but the new, unstained epithelium exhibited an abnormal pattern when observed under the specular microscope. Abnormally shaped cells, cells with nuclei, and white cells were observed, and normal maturation of the epithelial cells was disrupted. These abnormalities lasted more than eight months in three patients. Patient selection and careful follow-up is advised because of the abnormalities of the epithelium. PMID- 1895223 TI - Results of corneal pachymetry after small-incision hydrogel lens implantation and scleral-step incision poly(methyl methacrylate) lens implantation following phacoemulsification. AB - In a prospective study we used the change in central and peripheral (12 o'clock position) corneal thickness after two cataract surgery techniques as a parameter of tissue trauma. We looked at whether our findings indicated a difference in corneal thickness in the two groups and thus, as postulated in the literature, in the prospective endothelial cell loss. In 32 eyes (Group A) we performed small incision surgery (3.5 mm to 4.0 mm scleral-step incision) with hydrogel intraocular lenses implanted in the bag. In 30 eyes (Group B) we performed a 7.0 mm scleral-step incision with in-the-bag implantation of conventional poly(methyl methacrylate) intraocular lenses. Increases in corneal thickness (centrally and peripherally) were correlated after different postoperative periods. After 48 hours Group B showed a slightly higher increase in corneal thickness than Group A. Similar findings were observed at five days. In Group B the peripheral thickness did not show as high an increase as the central thickness after 48 hours. In all other cases the peripheral thickness increased more than the central thickness. After one month all eyes regained their preoperative thickness. We did not find a statistically significant difference in central and peripheral corneal thickness between the two groups. The results show that neither of the two surgical techniques greatly influenced the increase in corneal thickness and, consequently, the prospective endothelial cell loss. PMID- 1895224 TI - Intercapsular cataract surgery with lens epithelial cell removal. Part IV: Capsular fibrosis induced by poly(methyl methacrylate). AB - Characteristic lens epithelial cell behavior in the pseudophakic eye was examined by comparing 30 eyes that had extracapsular cataract surgery by the intercapsular technique and posterior chamber intraocular lens (IOL) implantation with lens epithelial cell removal but without anterior capsule capsulectomy and nine aphakic eyes that had the same procedure but without posterior chamber lens implantation over a mean follow-up period of 30 and 23 months, respectively. Fibrous anterior capsule opacification was observed in 83% of the pseudophakic eyes in the area of contact with the IOL, while the region beyond the margin of the IOL remained transparent. Fibrous anterior capsular opacification was not noted in the aphakic eyes. This suggests that the IOL material, poly(methyl methacrylate), stimulates lens epithelial cells to undergo fibrous metaplasia and to produce collagen fibers. Various cytokines such as IL-1 and TGF-beta synthesized by lens epithelial cells may play a crucial role as mediators in the process. We recommend that this effect be considered as a parameter of biocompatibility in developing and evaluating new biomaterials. PMID- 1895225 TI - Light and electron microscopic analysis of intraocular 2% hydroxypropylmethylcellulose. AB - Twenty samples of 2% hydroxypropylmethylcellulose for intraocular surgery, obtained from two Brazilian laboratories, were studied to determine the presence and type of impurities in the solutions. These were compared with ten samples of balanced salt solution (control group). Using light and scanning electron microscopy, five types of particles were identified: cellulose fibers, vegetable flakes, crystals, glass fragments, and other impurities. At least one of these contaminants was present in each sample of 2% hydroxypropylmethylcellulose. The vegetable matter was also seen in a sample of the raw material from which the clinical material had been prepared. Control solutions (i.e., balanced salt solution) were free of vegetable matter and of crystals, but glass fragments and other impurities were present. The average number of foreign particles in the solutions of hydroxypropylmethylcellulose (91.2 and 96.7 particles per milliliter for each of the two groups) was statistically greater than in the balanced salt solutions (13.7 particles per milliliter). PMID- 1895226 TI - Optical quality testing of monofocal intraocular lens implants with a 3 mm and a 4 mm aperture. AB - The optical quality of 81 monofocal poly(methyl methacrylate) intraocular lenses (IOLs) from eight U.S. firms was tested using a 3 mm aperture, as recommended by the American National Standards Institute Z80.7 standard for IOLs, and a 4 mm aperture. The use of the larger aperture had no effect on the measurements of refractive power and astigmatism. When examined with the 3 mm aperture, the average resolving power of the IOLs was 81% of the diffraction limit; when examined with the 4 mm aperture, the average resolving power was 67% of the diffraction limit. Use of the larger aperture would ensure that a larger area of the IOL had been examined. Incorporating the larger aperture into the ANSI minimum resolution requirement would not appreciably affect the rejection rate for currently manufactured monofocal lenses. PMID- 1895227 TI - Animal model experimentation using the expansile hydrogel intraocular lens. AB - To determine the biocompatibility of the expansile hydrogel intraocular lens, a two-year animal study was undertaken. After phacoemulsification, hydrogel expansile intraocular lenses were implanted in four Dutch-belted rabbit eyes. Slitlamp examinations revealed minimal anterior chamber reaction and lens synechias. Gross pathology and histology demonstrated hyperplastic residual cortex, but confirmed our clinical impression that the lenses were well tolerated. Electron diffraction energy dispersive X-ray microanalysis revealed deposition of aluminum, silicon, magnesium, and calcium, but there was no evidence of matrix penetration. PMID- 1895228 TI - Mycotic infection of the capsular bag in postoperative endophthalmitis. AB - A case of mycotic infection after uncomplicated extracapsular cataract extraction with implantation of a posterior chamber modified C-loop intraocular lens (IOL) is reported. Severe postoperative intraocular inflammation, diagnosed by aqueous cultures as secondary to Staphylococcus aureus endophthalmitis, did not respond to antibiotic therapy. Despite IOL and capsular bag removal and further antibiotic treatment, the inflammation persisted and phthisis followed. Retrospective electron microscopic examination of the explanted material demonstrated the presence of abundant fungal elements in the capsular bag and spores on the IOL surface. Vitreous taps performed at the time of explantation were negative for bacteria and fungi, confirming the localized nature of the mycotic infection. To our knowledge this report represents the first observation of a mycotic infection confined to the capsular bag after cataract surgery with implantation of a posterior chamber IOL. PMID- 1895230 TI - Anterior periocular anesthesia: five years experience. AB - Safe, effective administration of local anesthesia prior to ocular surgery is a primary concern of ophthalmologists and variations in the technique and method of delivering anesthesia have been developed. Retrobulbar anesthesia, although considered safe and effective, can have serious complications. Using periocular anesthesia eliminates some of the more serious complications associated with retrobulbar injections while still providing excellent anesthesia and akinesia. Results of over 3,600 periocular injections using the technique described are reported. PMID- 1895229 TI - Peribulbar anesthesia and optic nerve conduction. AB - Serial recordings of distance visual acuity and visually evoked potentials (VEPs) after peribulbar anesthesia in three patients are reported. Visual acuity was not markedly affected but the latency and amplitude of VEPs were. This study concludes that optic nerve conduction is not significantly affected by peribulbar anesthesia. PMID- 1895231 TI - Consultation section. Artificial lens implantation in the pediatric age group? PMID- 1895232 TI - Questionable authenticity and accuracy of Maguen excimer experiments. PMID- 1895233 TI - Positioning hole synechias with anterior chamber lenses. PMID- 1895234 TI - Calcium regulation of ciliary beat frequency in human respiratory epithelium in vitro. AB - 1. The changes in ciliary beat frequency (CBF) of human nasal respiratory epithelial cells were measured in vitro with a photometric technique following exposure to either 4-bromo-calcium ionophore A23187 (4-Br-A23187) or trifluoperazine (TFP), an inhibitor of calmodulin-sensitive calcium-dependent protein kinases. Changes in intracellular free calcium concentrations in response to 4-Br-A23187 were studied using a fluorescent dye (Fura-2). 2. Addition of 10( 5) M-4-Br-A23187 caused a time-dependent (P less than 0.01) rise in CBF. The increment in CBF was statistically significant 10 min after challenge (+10%; P less than 0.01) and was sustained for at least 1 h, with maximal stimulation after 40 min (+ 18%; P less than 0.01). 3. Exposure to 10(-5) M-4-Br-A23187 caused an immediate increase in intracellular free calcium concentration, which preceded the rise in CBF. 4. TFP (10(-4) M) caused a reduction of baseline CBF ( 10%; P less than 0.01) and prevented the expected rise when the cells were subsequently exposed to 10(-5) M-4-Br-A23187. 5. We conclude that: (1) calcium ionophore stimulates the CBF of human respiratory cells; (2) this effect is mediated through a calmodulin-sensitive system, since it is abolished in the presence of TFP; (3) the same pathway appears to control the basal CBF of these cells, since TFP also decreases CBF. PMID- 1895235 TI - Sensitivity and integration in a visual pathway for circadian entrainment in the hamster (Mesocricetus auratus). AB - 1. Light-induced phase shifts of the circadian rhythm of wheel-running activity were used to measure the photic sensitivity of a circadian pacemaker and the visual pathway that conveys light information to it in the golden hamster (Mesocricetus auratus). The sensitivity to stimulus irradiance and duration was assessed by measuring the magnitude of phase-shift responses to photic stimuli of different irradiance and duration. The visual sensitivity was also measured at three different phases of the circadian rhythm. 2. The stimulus-response curves measured at different circadian phases suggest that the maximum phase-shift is the only aspect of visual responsivity to change as a function of the circadian day. The half-saturation constants (sigma) for the stimulus-response curves are not significantly different over the three circadian phases tested. The photic sensitivity to irradiance (1/sigma) appears to remain constant over the circadian day. 3. The hamster circadian pacemaker and the photoreceptive system that subserves it are more sensitive to the irradiance of longer-duration stimuli than to irradiance of briefer stimuli. The system is maximally sensitive to the irradiance of stimuli of 300 s and longer in duration. A quantitative model is presented to explain the changes that occur in the stimulus-response curves as a function of photic stimulus duration. 4. The threshold for photic stimulation of the hamster circadian pacemaker is also quite high. The threshold irradiance (the minimum irradiance necessary to induce statistically significant responses) is approximately 10(11) photons cm-2 s-1 for optimal stimulus durations. This threshold is equivalent to a luminance at the cornea of 0.1 cd m-2. 5. We also measured the sensitivity of this visual pathway to the total number of photons in a stimulus. This system is maximally sensitive to photons in stimuli between 30 and 3600 s in duration. The maximum quantum efficiency of photic integration occurs in 300 s stimuli. 6. These results suggest that the visual pathways that convey light information to the mammalian circadian pacemaker possess several unique characteristics. These pathways are relatively insensitive to light irradiance and also integrate light inputs over relatively long durations. This visual system, therefore, possesses an optimal sensitivity of 'tuning' to total photons delivered in stimuli of several minutes in duration. Together these characteristics may make this visual system unresponsive to environmental 'noise' that would interfere with the entrainment of circadian rhythms to light-dark cycles. PMID- 1895236 TI - The influence of contralateral primary afferents on Ia inhibitory interneurones in humans. AB - 1. Contralateral influences on short latency reciprocal inhibition between wrist extensor and flexor muscles were investigated in twenty-two healthy volunteers. Reciprocal inhibition, probably mediated through the Ia inhibitory interneurone, was measured by conditioning the flexor carpi radialis (FCR) H reflex by weak stimulation of the ipsilateral radial nerve. Maximum reciprocal inhibition occurring at a precise delay between conditioning and conditioned stimulations was taken as the test level of inhibition. 2. Contralateral median or radial nerves were stimulated at short intervals before the onset of reciprocal inhibition. The latter was increased by 8.6% after median nerve stimulation and decreased by 16.5% after radial nerve stimulation. 3. The contribution of sensory fibres in the two nerves to contralateral effects was investigated by stimulating purely sensory branches of the nerves. No clear modification of the contralateral reciprocal inhibition was observed. The effects produced by mixed nerve stimulation are thus likely to have been mediated by Ia fibres. 4. In three hemiplegic patients where reciprocal inhibition was reduced unilaterally, stimulation on the spastic side produced contralateral effects similar to those observed in normal subjects. This result indicates that contralateral effects are not mediated through the Ia inhibitory interneurone ipsilateral to the conditioning stimulus. 5. Since contralateral effects occur after short delays (2 ms, median nerve; 3 ms, radial nerve), we suggest a functional scheme in which the excitability of Ia inhibitory interneurones is modified by contralateral primary afferents via the interneurones activated by group I fibres, probably Ia fibres. The short delays indicate that the interneurone transmitting primary afferent influences to the contralateral side is probably excitatory. PMID- 1895237 TI - Species-specific transfer of plasma albumin from blood into different cerebrospinal fluid compartments in the fetal sheep. AB - 1. The blood-cerebrospinal fluid (CSF) transfer of endogenous sheep albumin and several exogenous species of albumin has been investigated in different CSF compartments of the immature fetal sheep brain, at an early stage of development (60 days gestation, term is 150 days) when the CSF concentration of total protein is high. 2. There were marked differences in the steady-state CSF/plasma ratios for all species of albumin (including endogenous sheep albumin) between different CSF compartments. Ratios measured in the cisterna magna were significantly higher than those in the dorsal subarachnoid space, which in turn were higher than those in the lateral ventricles. The ratios for endogenous sheep albumin were (%; mean +/- S.E.M.): lateral ventricle (LV), 4.0 +/- 0.03; dorsal subarachnoid (DSA), 6.1 +/- 1.0; cisterna magna (CM), 13.7 +/- 0.8. 3. Three hours after I.V. injection, the CSF/plasma ratios for bovine albumin (LV, 2.0 +/- 0.2; DSA, 2.4 +/- 0.1; CM, 7.2 +/- 0.7%) were significantly lower than the ratio for endogenous sheep albumin in all three compartments. The ratios for human albumin (LV, 0.7 +/- 0.2; DSA, 1.0 +/- 0.2; CM, 3.9 +/- 0.4%) were significantly lower than those for bovine albumin. 4. In all three CSF compartments, the endogenous sheep albumin ratios were higher than would be expected on the basis of transfer by passive mechanisms. Conversely, steady-state CSF/plasma ratios for [3H]sucrose and [14C]inulin were consistent with passive transfer, and there were no differences between the ratios for these markers measured in each of the three CSF regions. 5. Goat albumin and [35S]sheep albumin ratios were not significantly different, 5 h after injection, from the endogenous sheep albumin levels in each of the three CSF compartments. 6. It is concluded that in the 60-day-old fetal sheep, all of the endogenous albumin in CSF is derived from the plasma by a specific transfer mechanism that can distinguish between different species of the same protein. There is also some evidence of a small passive component of blood-CSF albumin transfer. 7. Immunocytochemical evidence suggests that the route of transfer from blood to CSF is transcellular, through the choroid plexus epithelial cells. 8. Regional variations in albumin ratios are probably due to differences in specific transfer into each CSF compartment. This is reflected in a differential immunocytochemical staining for albumin in choroid plexus epithelial cells from different regions of the brain. 9. The results are discussed in terms of differences in albumin amino acid sequences, structural homologies, and transfer by a specific transcellular mechanism. PMID- 1895238 TI - Electrical responses of coronary artery smooth muscle associated with the cardiac muscle action potential in the monkey. AB - 1. In cardiac strips of the monkey ventricle which included a section of coronary artery (cardiac preparation), a depolarizing response, which appeared to be an excitatory junction potential (EJP), and a hyperpolarizing response were observed from the coronary artery smooth muscles when an action potential was generated in cardiac muscle by the application of electrical stimulation to the cardiac muscle alone. 2. In an isolated preparation of the coronary artery dissected from the ventricle (arterial preparation), similar responses, an EJP and a hyperpolarizing response, could be evoked by electrical stimulation. 3. In the cardiac preparation, the threshold of electrical stimulation for generation of the cardiac action potential and for production of an electrical response in the vascular smooth muscle were the same. 4. The EJP and the hyperpolarizing responses of the smooth muscle of the coronary artery ceased or were weakened by elimination of the adventitial connective tissues and endothelium, respectively, in both the cardiac preparation and the coronary artery preparation. 5. These results indicate that the action potential of cardiac muscle generated by electrical stimulation activates the nerves and the vascular endothelium, which, in turn, produce an EJP and a hyperpolarizing response of the coronary artery smooth muscle, respectively. PMID- 1895239 TI - Effects of vasoactive agonists on the membrane potential of cultured bovine aortic and guinea-pig coronary endothelium. AB - 1. The effects of bradykinin, ATP, adenosine, histamine and thrombin on the membrane potential of confluent monolayers of cultured bovine aortic endothelial cells (BAECs) and guinea-pig coronary endothelial cells (GCECs) were studied at 37 degrees C using the whole-cell mode of the patch-clamp technique. 2. The amplitude histogram of the resting potentials of BAEC monolayers showed a bimodal distribution with one peak around -25 mV and another peak around -85 mV. Transitions from one potential level to the other were observed. The bistable membrane potential can be explained by an N-shaped current-voltage relation of the endothelial cell membrane. 3. When BAECs with a low resting potential (-10 to -30 mV) were superfused with maximally effective concentrations of ATP (2-10 microM) an initial hyperpolarization of -80 to -90 mV was observed which decayed to a plateau of about -60 mV within 1 min. When ATP was removed after 2-3 min the membrane potential returned to control level within 1 min. This was followed by a second hyperpolarization of 10-20 mV, which decayed within 15 min. 4. In the absence of extracellular calcium, ATP produced only a brief transient hyperpolarization in aortic endothelium. The plateau and the secondary hyperpolarization were abolished. These findings are consistent with the idea that the changes in membrane potential reflect changes in intracellular free Ca2+ and that the initial peak is due to release of Ca2+ from intracellular stores, whereas the plateau and the secondary hyperpolarization depend on transmembrane Ca2+ influx. 5. Bradykinin evoked potential changes similar to ATP in BAECs, except that the secondary hyperpolarization during wash-out was absent. When the membrane potential was more negative than -80 mV, ATP and bradykinin induced only a small initial hyperpolarization followed by a depolarization of up to 20 mV. 6. In aortic endothelium, ADP (10 microM) evoked a much smaller response than ATP. Adenosine (10 microM), thrombin (2 units/ml), acetylcholine (10 microM) and histamine (10 microM) had only a very small effect on the membrane potential, if any. 7. The amplitude histogram of the membrane potential of GCECs showed only one peak around -35 mV. In coronary endothelium, application of bradykinin, ATP, histamine, thrombin, acetylcholine and adenosine all evoked a transient hyperpolarization of 10-40 mV lasting 1 min or less, which then turned into a depolarization. 8. The K+ channel openers cromakalim (BRL 34915) and lemakalim (BRL 38227) did not affect the membrane potential of GCECs or BAECs.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1895240 TI - Endoneurial blood flow in rat sciatic nerve during development. AB - 1. Endoneurial blood flow (EBF) in the sciatic nerve of rats aged 2-12 weeks was studied using microelectrode H2 polarography. 2. EBF is highest in 2-week-old rats and progressively declines during development. Mean arterial pressure (MAP) is low at 2 weeks of age, gradually increases through the next 4 weeks, and is relatively constant thereafter. The decrease in EBF, in spite of an increase in MAP, occurs because the endoneurial vascular resistance is increasing faster than the MAP. 3. The higher EBF in younger rats is not due to the smaller diameter of their nerves. Sural and tibial nerves of 12-week-old rats, with diameters comparable to that of the sciatic nerve of a 3-week-old rat, have EBFs similar to that of the sciatic nerve of a 12-week-old rat. 4. There was no compelling evidence of autoregulation of EBF in 3-week-old rats over a MAP range from -40 to +30 mmHg of the normal value. 5. The increase of nerve vascular resistance with maturation is probably due to a decrease in capillary density and, to a lesser extent, to an increase in plasma viscosity and haematocrit. 6. The higher EBF in immature rats is likely to be a developmentally adaptive mechanism which permits greater blood-nerve exchange of material to accommodate the greater metabolic needs of rapidly elongating and myelinating axons and proliferating Schwann cells. PMID- 1895241 TI - Optical determination of impulse conduction velocity during development of embryonic chick cervical vagus nerve bundles. AB - 1. Employing an optical method for multiple-site simultaneous recording of electrical activity, we have determined the conduction velocity in cervical vagus nerve bundles isolated from 5- to 21-day-old chick embryos, and investigated its developmental changes. 2. The preparations were stained with a voltage-sensitive merocyanine-rhodanine dye (NK2761), and action potential- (impulse-) related optical signals were elicited by brief stimuli applied to the end of the vagus nerve bundle with a suction electrode. Optical signals were recorded simultaneously from many contiguous regions using a 12 x 12-element photodiode array. 3. The optical signals spread with small delay from the site of stimulation. From the relationship between the delay and distance from the current-applying electrode, conduction velocities were estimated in each tested preparation: the conduction velocity was very small and increased monotonically from about 0.1 m s-1 at 5 days embryonic age to about 0.4 m s-1 by hatching. The increase in the conduction velocity was closely related to a developmental increase in the diameter of the vagus nerve bundle. 4. In addition, we have examined the spread of electrotonic potentials. The space constant was very small (200-450 microns) and increased as development proceeded. 5. Compound optical action signals having two distinct components were also recorded. They often appeared to be concentrated in the preparations from 8- to 12-day-old embryos. The conduction velocity of the second component was slower than that of the first. We suggest that appearance of the second component reflects degeneration of a subset of axons resulting from 'neural cell death' during the development of the vagus nerve. PMID- 1895242 TI - Extracellular K+ in the supraoptic nucleus of the rat during reflex bursting activity by oxytocin neurones. AB - 1. We have investigated changes in extracellular potassium concentration [K+]o in the supraoptic nucleus of lactating rats and in particular those that occur during the intense burst of firing by the oxytocin neurones involved in the milk ejection reflex. 2. Double-barrelled K(+)-selective microelectrodes containing a highly selective sensor based on valinomycin were lowered through the exposed cortex towards the supraoptic nucleus (SON) of female rats anaesthetized with urethane. The mean resting [K+]o in the hypothalami of five rats was 2.4 mM, S.D. = 0.3 mM. 3. Where the reference barrel recorded extracellular action potentials from an oxytocin cell, the reflex burst of firing (4 s, typical maximum 50 Hz) was accompanied by a mean increase in [K+]o (delta[K+]o) of 0.22 mM (S.E.M. = 0.02 mM, fifty-seven bursts in eight cells in seven rats). The rise in [K+]o did not begin more than 0.1 s before the onset of the burst, and began to fall from its maximum during the burst. Slow field potentials, indicative of spatial buffering of K+, were undetectable (less than 50 microV). When the electrode was advanced in steps, the amplitudes of both delta[K+]o and the action potential declined steeply to about 10% over a distance of 20 microns: K+ from oxytocin cells appears to be prevented from dispersing freely through the extracellular space of the SON. 4. When the electrode recorded action potentials from a vasopressin cell, delta[K+]o during an oxytocin cell burst was very small: 0.021 mM (S.E.M. = 0.005 mM). At other sites in the SON, where antidromic stimulation evoked a field potential but no action potential, delta[K+]o was 0.047 +/- 0.005 mM. We conclude that the reason oxytocin bursts do not affect vasopressin cells is that [K+]o rises very little around vasopressin cells. A fortiori, since the increases in [K+]o were very small except where action potentials from oxytocin cells were recorded, they can make no significant contribution to synchronizing the onsets of bursts in oxytocin cells that are not contiguous. 5. A standard antidromic stimulation from the pituitary stalk, at 40 Hz for 4 s, which stimulated both oxytocin neurones and vasopressin neurones, caused a delta[K+]o of 0.17-1.8 mM, the variation being mainly from rat to rat. The larger delta[K+]o values were accompanied by slow negative potentials of up to 1.5 mV, there was a gradient in delta[K+]o decreasing towards the pia at the inferior limit of the SON, and there was a slow increase in [K+] in the subarachnoid space.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1895243 TI - The mechanism of prediction in human smooth pursuit eye movements. AB - 1. Experiments have been conducted on human subjects to determine the role of prediction in smooth eye movement control. Subjects were required to actively pursue a small target or stare passively at a larger display as it moved in the horizontal plane. 2. Target motion was basically periodic, but, after a random number of cycles an unexpected change was made in the amplitude, direction or frequency of target motion. Initially, the periodic stimulus took the form of a square waveform. In subsequent experiments, a triangular or sawtooth waveform was used, but in order to examine the timing of the response in relation to stimulus appearance, the target was tachistoscopically illuminated for 40-320 ms at the time that it passed through the mid-line position. 3. When subjects either actively pursued the target or stared passively at the larger display a characteristic pattern of steady-state eye movement was evoked composed of two phases, an initial build-up of eye velocity that reached a peak after 200 ms, followed by a decay phase with a time constant of 0.5-2 s. The build-up phase was initiated prior to target displacement for square-wave motion and before onset of target illumination for other waveforms. 4. The peak eye velocity evoked gradually increased over the first two to four cycles of repeated stimulation. Simultaneously, the response became more phase advanced, the reaction time between stimulus onset and the time at which peak velocity occurred decreasing from an average of 300 to 200 ms for triangular waveform stimuli. 5. When there was a sudden and unexpected change in amplitude and direction of the stimulus waveform, the eye movement induced had a peak velocity and direction that was inappropriate for the current visual stimulus, but which was highly correlated with the features of the preceding sequence in the stimulus. 6. When there was a sudden change in the frequency of the stimulus waveform the predictive eye movement was induced with a timing appropriate to the periodicity of the previous sequence but inappropriate to the new sequence. 7. The results indicate that prediction is carried out through the storage of information about both the magnitude and timing of eye velocity. The trajectory of the averaged eye velocity response was similar in form irrespective of the duration of target exposure or basic stimulus frequency, suggesting that the predictive estimate is released as a stereotyped volley of constant duration but varying magnitude under the control of a periodicity estimator.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1895244 TI - The cortical drive to human respiratory muscles in the awake state assessed by premotor cerebral potentials. AB - 1. We investigated the possibility of a cortical contribution to human respiration by recording from the scalp of awake subjects the premotor cerebral potentials that are known to precede voluntary limb movements. 2. Electroencephalographic activity (EEG) was recorded from scalp electrodes and averaged for 1.8-2.0 s before the time at which airway pressure exceeded an inspiratory or expiratory threshold. Clear premotor cerebral potentials were recorded during brisk, self-paced nasal inhalations or exhalations. In ten subjects, a slow cortical negativity (Bereitschaftspotential) was apparent in the averaged EEG, commencing 1.2 +/- 0.3 s before the onset of inspiratory (scalene) or expiratory (abdominal) muscle activity (EMG). It was maximal at the vertex, with a mean slope of 12.3 +/- 5.8 microV/s, and was followed by a post-movement positivity. 3. In four subjects the inspiratory premotor potential culminated in a large negativity, the motor potential, which began 24 +/- 15 ms before the onset of scalene EMG. It is argued that such a short latency is consistent with a volitionally generated respiratory command which travels relatively directly to the respiratory muscles, having a total central delay which is no longer than that for voluntary finger movements. 4. That the respiratory premotor and motor potentials did not originate in subcortical structures was supported by their absence in a patient suffering from chronic reflexogenic hiccups, in whom cerebral activity was back-averaged from each brisk hiccup. 5. During quiet breathing, in which subjects were relaxed and distracted from thinking about their respiration, no premotor cerebral potentials preceding inspiration could be detected. This failure was not due to the slow rate of rise of inspiratory activity during quiet breathing as compared with a brisk sniff, because premotor potentials were detected when subjects intermittently generated slow active expiratory efforts. 6. These observations suggest that during quiet breathing the cerebral cortex does not contribute to respiratory drive on a breath-by-breath basis. Conversely, the presence of clear premotor cerebral potentials when subjects performed self-paced inspiratory or expiratory manoeuvres illustrates the powerful cortical projection to human respiratory muscles. PMID- 1895245 TI - Some reflex cardioinhibitory responses in the cat and their modulation by central inspiratory neuronal activity. AB - 1. Cats were anaesthetized with a mixture of chloralose and urethane, and were artifically ventilated. 2. An open pneumothorax was provided by two large-bore tubes which were sealed in the sixth intercostal space on each side. They were connected to a Fleisch pneumotachograph. Phasic changes in central inspiratory neuronal activity were measured quantitatively as changes in the volume of the pneumothorax during temporary interruption of artificial respiration, the volume of the lungs being held constant at their end-expiratory level. In this way the activity of slowly adapting pulmonary stretch receptors was maintained constant. 3. Reflex cardioinhibitory responses were elicited by stimulation of (a) the carotid body chemoreceptors by intracarotid injections of cyanide; (b) the arterial baroreflex by controlled elevations of the blood pressure; (c) cardiac receptors by left atrial injections of veratridine; and (d) pulmonary C fibres (including J receptors) by right atrial injections of phenylbiguanide. 4. The effects of central inspiratory neuronal activity on pulse interval were assessed by comparing the values observed during the inspiratory and expiratory phases of the respiratory cycle in the control state and during stimulation of each cardiovascular receptor group. 5. The carotid chemoreceptor-induced bradycardia measured during the expiratory phase of respiration was reduced during inspiration to a value of about 15% of control. The central inspiratory drive was less effective in altering the reflex responses from the arterial baroreceptors and cardiac receptors, the corresponding values being 42 and 51% respectively. 6. In contrast, the bradycardia evoked by pulmonary C fibre stimulation was not significantly affected by the central inspiratory drive. 7. The differential nature of the modulation by the central inspiratory drive occurred independently of the integrity of the sympathetic nerve supply to the heart indicating that the cardiac efferents involved were largely fibres in the vagus nerves. 8. The possible explanation of these results in terms of central mechanisms is discussed. PMID- 1895246 TI - Activation and inactivation of excitation-contraction coupling in rat soleus muscle. AB - 1. Potassium (K+) contractures have been used to characterize the processes of activation and inactivation of excitation-contraction coupling during prolonged depolarization of fibres in small bundles dissected from rat soleus muscles at 23 degrees C. 2. The smallest measurable K+ contracture tension was recorded with depolarization to -40 mV in 30 mM-K+ and maximum tension was achieved between -26 mV in 80 mM-K+ and -19 mV in 120 mM-K+. 3. The rate of inactivation of K+ contracture tension was voltage dependent. Tension decayed from 80 to 20% of the peak amplitude within 44.0 +/- 2.2 s at -26 mV (in 80 mM-K+), compared with 66.7 +/- 4.8 s at -35 mV (in 40 mM-K+). Results are given as mean +/- 1 S.E.M. 4. The effect of inactivation on maximum tension was determined using a two pulse protocol in which a 'conditioning' depolarization in solutions containing 20-120 mM-K+ was applied for 0.5-10 min before a 'test' depolarization to -8 mV in 200 mM-K+. The amplitude of the test contracture was compared with the mean amplitude of 'control' 200 mM-K+ contractures elicited in normally polarized fibres immediately before and after the two pulse protocol. Conditioning depolarization to -47 mV (in 20 mM-K+) did not reduce test 200 mM-K+ contracture tension. Significant inactivation was seen with further conditioning depolarization to more positive potentials: after 10 min at -40 mV (in 30 mM-K+), or -35 mV (in 40 mM-K+), test 200 mM-K+ contracture tension was reduced by 33 and 70% respectively. 5. In contrast to amphibian muscle, where maximum tension falls to zero within a few minutes of depolarization to potentials positive to -50 mV, test 200 mM-K+ contracture tension in rat soleus fibres fell initially rapidly and then slowly, but was not reduced to zero, even after 10 min at -19 mV in 120 mM-K+. 6. The fast phase of inactivation of test 200 mM-K+ contracture tension occurred during the decay of the conditioning K+ contracture. The slow phase of inactivation reached completion after 10 min of conditioning depolarization and occurred during the period when conditioning tension was reduced to zero or to a plateau level. Both phases of inactivation in rat soleus fibres are slow compared with fast and slow inactivation times of 5-100 s respectively reported for amphibian muscle. 7. When repolarized after prolonged depolarization, the muscle fibres were initially refractory, i.e. unable to produce tension in response to electrical stimulation.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1895247 TI - C-protein limits shortening velocity of rabbit skeletal muscle fibres at low levels of Ca2+ activation. AB - 1. Effects on maximum shortening velocity (Vmax) due to partial extraction of C protein were investigated in skinned fibres from rabbit psoas muscles. Up to 80% of endogenous C-protein was extracted, as assessed by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) of fibre segments obtained before and after the extraction protocol. Vmax was obtained at 15 degrees C by measuring the times required to take up various amounts of slack imposed at one end of the fibre. 2. During maximal activation with Ca2+, Vmax in control fibres was 4.26 +/ 0.16 (mean +/- S.E.M., n = 7) muscle lengths per second (ML/s). Following extraction of approximately 40% of endogenous C-protein, Vmax in these same fibres was 4.41 +/- 0.24 ML/s. 3. At sufficiently low levels of submaximal activation, high- and low-velocity phases of unloaded shortening were observed. Partial extraction of C-protein significantly increased Vmax in the low-velocity phase but had no effect on the high-velocity phase. The effect on low-velocity Vmax was fully reversed by re-addition of purified C-protein. 4. At low levels of activation, the amount of shortening to the break-point between the high- and low velocity phases was not significantly affected by C-protein extraction. Under control conditions the average break-point was 85.6 +/- 3.1 nm/half-sarcomere, while 84.1 +/- 3.1 nm/half-sarcomere was obtained following partial extraction of C-protein. 5. These results are considered in terms of a model in which an internal load slows Vmax at low levels of activation once a given amount of active shortening has occurred. C-protein may contribute to this internal load either by binding to actin and myosin or by influencing mechanical properties of myosin cross-bridges. PMID- 1895249 TI - Ameloblastomas originating from odontogenic cysts. PMID- 1895248 TI - Differential control of the inspiratory intercostal muscles during airway occlusion in the dog. AB - 1. The effect of airway occlusion on the electrical activity of the three groups of inspiratory intercostal muscles (external intercostal, levator costae, parasternal intercostal) situated in the cranial portion of the rib-cage has been studied in thirty anaesthetized, spontaneously breathing dogs. 2. The three muscles were active during normal inspiration, and their activity was prolonged similarly during airway occlusion. However, a comparison of activity during occluded and unoccluded inspirations indicated that airway occlusion caused a facilitation of external intercostal and levator costae activities but an inhibition of parasternal intercostal activity. 3. The facilitation of external intercostal and levator costae activities was markedly reduced after section of the phrenic nerves and completely suppressed after section of the appropriate thoracic dorsal roots. 4. The inhibition of parasternal intercostal activity was not affected by section of the phrenic nerves or by section of the thoracic dorsal roots. This phenomenon, however, was abolished after bilateral cervical vagotomy. 5. Activation of the external intercostals and levator costae during inspiratory efforts are thus highly dependent on segmental reflexes arising in these muscles. In contrast, activation of the parasternal intercostals resembles that of the diaphragm in the sense that it depends primarily on the central respiratory drive. PMID- 1895250 TI - Effect of calcitonin on alveolar wound healing. AB - The effect of calcitonin (CT) on alveolar wound healing was studied with histomorphometric methods. Wistar rats weighing 80-90 g were submitted to extraction of the three mandibular molars. Half of them were injected intraperitoneally with daily therapeutic doses of CT. The control group received no further treatment. All the rats were killed 14 days after the onset of the experiment. Bone healing was impaired in CT treated animals and involved a more intense bone remodeling activity. Bone resorptive areas were present both on the profiles of the newly formed bone and on the alveolar ridge surface. These results suggest that CT would accelerate the process of bone healing. PMID- 1895251 TI - Phenotyping of immunocompetent cells in normal labial and palatal salivary glands and in non-autoimmune sialadenitis. AB - Different types of inflammatory cells in healthy major and minor salivary glands (SG), including those in labial and palatal non-autoimmune sialadenitis, were quantified immunohistochemically. Plasma cells, mainly IgA type predominated in all SG types, with the smallest number seen in the palatal glands. The numbers of common leukocyte antigen (CLA) reactive lymphocytes were greater in major SGs than in minor ones and were predominantly UCHL1 positive T cell type. Macrophages and neutrophils were absent in palatal glands, rarely present in labial ones and usually present in major SGs. Increases in the number of IgG and IgM plasma cells and lymphocytes (CLA+) which include both UCHL1+ T and L26+ B cell types, were found in non-autoimmune labial and palatal sialadenitis. There was no significant correlation between the number of the inflammatory cells and the degree of glandular atrophy in both labial and palatal non-autoimmune sialadenitis. Increase in their number represents a protective response of these glands in contrast to the inflammatory cells in major autoimmune sialadenitis playing there a pathogenetic role. PMID- 1895252 TI - Permanent teeth in hypophosphatasia: light and electron microscopic study. AB - The changes in a permanent central incisor of a patient suffering from hypophosphatasia, were investigated light microscopically and compared with those of two of his primary teeth. In addition his other central incisor was studied with transmission and scanning EM. The changes in permanent teeth were similar to those of the primary dentition, including loss of cementum and the presence of deep resorption areas in dentin. Afibrillar cementum was detected with EM, and was attached to dentin surface. The presence of a thick layer of bacterial plaque was a prominent feature in all the teeth examined. A large number of bacteria was also found in resorption bays. It is suggested that bacteria may play an important role in the destruction of soft and hard tissues leading to loss of teeth in hypophosphatasia. PMID- 1895253 TI - Enhanced killing effect on 5-bromodeoxyuridine labelled bacteriophage T1 by monoenergetic synchrotron X-ray at the energy of bromine K-shell absorption edge. AB - 5-Bromo-2'-deoxyuridine labelled bacteriophage T1 was irradiated with monoenergetic X-rays obtained from synchroton radiation with the energies at 13.51 keV and 12.40 keV, just above and below the K-shell absorption edge (13.41 keV) of bromine, respectively. Phage samples were irradiated under three conditions, wet N2 gas, dry N2 gas and in vacuum, with water contents (g H2O/g sample) of 60, 2.6 and 0%. At 12.40 keV the D0 in kGy were 1.1 ("wet"), 1.9 ("dry") and 2.5 ("vacuum") for the Br-labelled phages and 1.6 ("wet"), 2.4 ("dry") and 6.2 ("vacuum") for unlabelled phages. The results clearly demonstrated that the X-ray sensitivities decreased with decrease in water contents. Br-enhancement ratios, ER = D0 (unlabelled)/D0 (Br-labelled), varied from 1.4 ("wet", 12.40 keV) to 2.5 ("vacuum", 13.51 keV). Auger enhancements which were defined by energy-dependent enhancement factor, Fen = [ER(13.51 keV) ER(12.40 keV)]/ER(12.40 keV), were 0.09 +/- 0.09, 0.29 +/- 0.07 and 0.02 +/- 0.03 under "wet", "dry" and "vacuum" conditions, respectively. The change in Auger enhancement under "dry" condition in comparison with "wet" condition could be explained due to less of water. However the Auger enhancement decreased sharply under "vacuum" condition as the water content was zero. The reason for the sharp decrease in Auger enhancement under "vacuum" condition is difficult to understand. A possible explanation is discussed in the text. PMID- 1895254 TI - Gamma-ray- and fission neutron-induced micronuclei in PHA stimulated and unstimulated human lymphocytes. AB - Two groups of normal human blood cells, one stimulated with phytohaemagglutinin (PHA) for 24 hr (G1-S phase of the cell cycle) and one unstimulated (G0 phase), were irradiated with 60Co gamma rays or 252Cf radiation. A comparison of radiation-induced micronucleus frequencies showed that the high-dose-rate gamma rays were more effective in inducing micronuclei than low-dose-rate gamma rays. In the cells exposed to low-dose-rate irradiation, there was little difference between the frequency of micronuclei in the G0 phase and the G1-S phase. However, cells in the G1-S phase were more sensitive than G0-phase cells to high-dose-rate gamma rays. The relative biological effectiveness of 252Cf neutron irradiation measured in micronucleus assays was consistent with the value obtained for the lethal effect of 252Cf on cultured cells. PMID- 1895255 TI - Split-dose effect of X-irradiation on the induction of cell death in the fetal mouse brain. AB - Pregnant mice were exposed to whole-body X-irradiation at a total dose of 0.25 Gy split into two 0.125 Gy exposures at 0.5-, 2- or 6-hour interval on day 13 of pregnancy. Fetuses were obtained from dams at various post-exposure periods and their brains were processed for microscopy. Undifferentiated neural cells in the ventricular zone of telencephalon (ventricular cells) were examined, and incidence of cells involved in pyknosis was evaluated. The curves of incidence of pyknotic cells plotted against time after the exposures to two split-doses at 0.5 hour and 2-hour intervals overlapped that of a single 0.25 Gy exposure; they had a common peak at 8-10 hours after the first exposure. Following two 0.125 Gy exposures at 6-hour interval, two peaks with similar elevations from background levels appeared at 6 and 12 hours after the first exposure. These results indicated that low-dose X-irradiation shows simply additive effects of split doses on cell death, without induction of adaptive response of ventricular cells of the telencephalon at day 13 of pregnancy in mice. PMID- 1895256 TI - The developing relationship between the World Health Organization and the International League Against Rheumatism. PMID- 1895257 TI - NSAID gastropathy--not just a pain in the gut! PMID- 1895258 TI - Drug induced pseudoporphyria. PMID- 1895260 TI - Predictors of fractures in early rheumatoid arthritis. AB - Three hundred ninety-five patients with rheumatoid arthritis (mean age 49 years) were followed for an average of 6.7 years, and their baseline variables from the initial visit were examined for prediction of time to first fracture. Multivariate analyses identified use of corticosteroids in women and prior diagnosis of osteoporosis as important risk factors. Among patients taking 5 mg or more of prednisone, female sex strongly predicted fractures: the 5-year probability of having a fracture was 34%. Low risk groups were nonosteoporotic and consisted of men and patients taking less than 5 mg prednisone. PMID- 1895261 TI - Occurrence of neoplasia in patients with rheumatoid arthritis enrolled in a DMARD Registry. Rheumatoid Arthritis Azathioprine Registry Steering Committee. AB - The Rheumatoid Arthritis Azathioprine Registry (RAAR) was established in 1982 to examine the safety of azathioprine (AZA) and other disease modifying agents (DMARD) in the treatment of RA. In yearly followup over the past 7 years, 20 malignant conditions have been reported in 530 DMARD treated adult patients with RA. Incidence density ratios (IDR) and standardized morbidity ratios (SMR) were calculated to assess cancer risk. For all cancers the SMR was 1.52 (95% CI 0.90 2.60). For men the SMR was 1.71 (95% CI 0.84-3.52); for women the SMR was 1.52 (95% CI 0.89-2.60). Adjusted for age, the IDR was highest in the 70-79-year-old study population (3.41). The age and sex adjusted SMR for lymphoproliferative disorders and myeloma was 8.05 (95% CI 3.30-20.81). The SMR for lung cancer (n = 6) was also increased (3.37; 95% CI 1.58-7.34). Compared with the general population, patients with RA requiring DMARD therapy may be at increased risk of malignancy, particularly lymphoproliferative disorders. The RAAR is an important prospective technique which will ultimately permit assessment of neoplasia risk by type and duration of DMARD therapy. PMID- 1895259 TI - Rheumatoid arthritis in Israeli Jews: shared sequences in the third hypervariable region of DRB1 alleles are associated with susceptibility. AB - Rheumatoid arthritis (RA) is known to be associated with class II HLA antigens in most populations, but recent studies in Israeli Jewish patients showed no significant differences in either DR4 or DR1 between patients and controls. In a previous DR4 subset study we found DR4-Dw15 to be associated with susceptibility (RR = 9.2) but this allele occurred in only 12% of the patients. We analyzed all DRB1 genes, using the polymerase chain reaction (PCR) and hybridization with allele specific oligonucleotides, in 49 Jewish patients with RA and 40 normal Jewish controls. Six DRB1 alleles that are similar to the prototype DR4-Dw4 (DRB1*0401) appeared to contribute to the risk for developing RA. In addition to DR4-Dw15 (DRB1*0405) 2 other alleles having substitutions in codons 71 only (DR1 Dw1/DRB1*0101, DR4-Dw14.2/DRB1*0408) or in codons 70 and 71 (DRw10/DRB1*1001) gave highly significant relative risks. Together, this group, with valine in position 85, and glycine in codon 86, gave a relative risk of 11.0 (p = 0.0002). Two other alleles with the same sequence in the third hypervariable region (amino acids 67-74) but with valine in codon 86 (DR4-Dw14.1/DRB1*0404) or alanine in 85 and valine in 86 (DR1-Dw20, DRB1*0102) gave a combined risk of 3.6 (p = 0.049). Altogether these 7 alleles with similar sequences in the third hypervariable region accounted for 55.6% of the patients, with an overall relative risk of 8.6 (p = 0.00002). Our results in this population indicate that shared epitopes in the third hypervariable region of DRB1 alleles also play a role in susceptibility to RA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1895262 TI - Comparison of cyclosporine and D-penicillamine for rheumatoid arthritis: a randomized, double blind, multicenter study. AB - Ninety-two patients with active rheumatoid arthritis (RA) were entered in a randomized double blind study of 24 weeks comparing cyclosporine (initial daily dose 5 mg/kg) with D-penicillamine (initial daily dose 250 mg). The groups were well balanced in baseline characteristics. In the cyclosporine group, 10 patients stopped prematurely, one because of inefficacy. In the D-penicillamine group, 9 patients stopped prematurely, 3 because of inefficacy. The 2 antirheumatic drugs were equally effective in reducing disease activity, except for a significant (p = 0.005) decrease in erythrocyte sedimentation rate with D-penicillamine treatment. We conclude that under the conditions of this trial, cyclosporine can serve as an alternative to D-penicillamine for the treatment of patients with RA. PMID- 1895263 TI - Response to glucocorticoid treatment in rheumatoid arthritis: in vitro cell mediated immune assay predicts in vivo responses. AB - Variable treatment responses to glucocorticoids occur in patients with rheumatoid arthritis (RA). In renal transplantation and asthma treatment responses correlate with in vitro tests of glucocorticoid immunosuppression. We compared in vitro methylprednisolone suppression of concanavalin A stimulated cellular proliferation with clinical responses to methylprednisolone in patients with RA. Patients found to be glucocorticoid sensitive by in vitro testing had significantly greater improvements in joint score and soluble interleukin 2 receptor (sIL-2R) levels compared to control patients, indicating that individual responsiveness to glucocorticoid exists in RA. Similar in vitro and in vivo changes of sIL-2R levels suggests that they reflect cell mediated immune events in vivo. PMID- 1895264 TI - Rheumatoid factor, cryoglobulinemia, anti-DNA, and renal disease in patients with systemic lupus erythematosus. AB - We retrospectively analyzed the relationship between rheumatoid factor (RF) and renal disease in 102 patients with systemic lupus erythematosus (SLE). We found a significant negative association between detectable RF at any time in a patient's course and clinically significant renal diseases. Multivariate analysis indicates that RF and cryoglobulins, operating independently, have a significant and opposite association with the development of renal disease in patients with SLE. These associations appear to be unrelated to the presence or absence of anti-ds DNA (anti-DNA). Patients with SLE who are RF negative and cryoglobulin positive are likely to develop renal disease whereas those who are RF positive and cryoglobulin negative are very unlikely to do so. The addition of RF and cryoglobulin determinations to the data base of patients with SLE appears to be clinically useful. PMID- 1895265 TI - The impact of increased contact on psychosocial outcomes in patients with osteoarthritis: a randomized, controlled trial. AB - After baseline in home interviews, 439 patients with osteoarthritis (OA) were randomly assigned to the control or one of 3 intervention groups which differed only in method of delivery (i.e., phone, clinic, both). Trained nonclinical interviewers reviewed medications, problems with joint pain, gastrointestinal symptoms, early warning signs for common chronic diseases, scheduled outpatient visits, an evening/weekend clinic telephone number, barriers to care, and suggestions to encourage participation during clinic visits. We hypothesized that the intervention would enhance social support, satisfaction with care, morale, and medication compliance. We found that none of the interventions had any effect upon these outcomes. PMID- 1895267 TI - Hydroxyapatite crystals are a frequent finding in osteoarthritic synovial fluid, but are not related to increased concentrations of keratan sulfate or interleukin 1 beta. AB - Synovial fluid (SF) was obtained from 40 patients with varying grades of osteoarthritis (OA) of the knee and examined by transmission electron microscopy to ascertain how frequently hydroxyapatite crystals (HA) were present and whether they were related to disease severity or putative markers or promoters of cartilage resorption. HA crystals were conspicuous and abundant in specimens from 21 of the 40 patients studied. Patients in whom HA was present had significantly larger effusions (13.0 +/- 8.9 vs 8.7 +/- 6.1 ml, p less than 0.05). They also tended to have radiologically more severe disease (radiological grade: 2.91 +/- 0.92 vs 2.39 +/- 0.85, p = 0.056). No difference in keratan sulfate (KS) concentrations was observed. Moreover, despite the presence in some specimens of numerous free histiocytes which were actively phagocytosing HA aggregates, the concentrations of interleukin 1 beta (IL-1 beta), a monocyte product with cartilage and bone resorbing activity, were below the limit of detection (20 pg/ml). Our results confirm that HA crystals are a common finding in patients with OA of the knee and show that HA is associated with larger effusions, but not increased SF concentrations of cartilage proteoglycan substituents (KS) or IL-1 beta. PMID- 1895266 TI - Antiinflammatory and antiarthritic properties of a substituted quinoline carboxylic acid: CL 306,293. AB - CL 306,293, a substituted quinoline carboxylic acid at a daily oral dose between 1.5 and 3.0 mg/kg suppressed the inflammation and joint destruction (radiological criteria) associated with both developing and established adjuvant arthritis. When a weekly oral dosing regimen was used, joint destruction was attenuated when this agent was administered at a dose of 50 to 200 mg/kg. Inflammation associated with a delayed type hypersensitivity reaction in dogs was suppressed at a daily dose of 0.25 mg/kg or a weekly dose of 1 mg/kg. At efficacious doses, CL 306,293 had no effects on cyclooxygenase or lipoxygenase activities nor did it have an effect on carrageenin induced paw edema. In acute tests, the compound was not ulcerogenic. The above observations indicate that the antiinflammatory effects of CL 306,293 are distinct from those observed with nonsteroidal antiinflammatory agents. Mechanistic studies conducted and to be published indicate that CL 306,293 down regulates T cell function and this mechanism may account, at least in part, for the antiinflammatory and antiarthritic properties observed in animal models of inflammation and joint destruction. PMID- 1895268 TI - Juvenile progressive systemic sclerosis: report of five cases. AB - Five cases of juvenile progressive systemic sclerosis (SSc) are reported (4 girls and 1 boy). The age of onset of the disease ranged from 4 to 13 years. The clinical features included Raynaud's phenomenon present in 4 of 5 cases; hyperpigmentation, skin tightening and contractures of the large joints were noted in all 5 cases. One patient initially diagnosed as having eosinophilic fasciitis developed SSc 3 months later. Another patient was diagnosed initially as having juvenile rheumatoid arthritis. There was one case of pulmonary fibrosis and another of mild restrictive lung disease. Two cases of esophageal and intestinal hypomotility were reported. Scleroderma nephropathy was absent in all 5 cases. PMID- 1895269 TI - Distal interphalangeal joint abnormalities in children with polyarticular juvenile rheumatoid arthritis. AB - Involvement of the distal interphalangeal (DIP) joints was noted radiographically in 24 (43.6%) of 55 patients with polyarticular juvenile rheumatoid arthritis. DIP changes were apparent later in the course of the disease and were less severe than in other affected joints. Soft tissue swelling and joint space narrowing were the most frequent abnormalities in the DIP joints. Erosive changes and angular deformities were uncommon. There was no significant correlation between DIP joint involvement and sex, age at presentation, involvement of the hands and wrists at presentation, or positivity of either rheumatoid factor or antinuclear antibody. There was a strong correlation between the presence of extraarticular signs and symptoms and involvement of the DIP joints; however, this may reflect the greater severity of the disease in these patients generally. PMID- 1895271 TI - Air esophagogram and intestinal pseudoocclusion in a patient with scleroderma. AB - Air in the esophagus is unusual because it is collapsible. Its finding on a chest roentgenogram, particularly when not associated with a fluid level indicative of stricture, should strongly suggest systemic sclerosis (scleroderma). We describe a patient with scleroderma with intestinal pseudoocclusion and an air esophagogram. Study of chest roentgenograms of 83 patients with scleroderma, including those of 7 with pseudoocclusion, revealed no other instance of air esophagogram. This radiological sign, although rare, should suggest scleroderma and may be particularly useful in patients with "systemic sclerosis sine scleroderma." PMID- 1895270 TI - Naproxen induced pseudoporphyria in juvenile chronic arthritis. AB - We report 6 cases of porphyria-like skin reactions in children taking naproxen for juvenile chronic arthritis. The lesions mimicked either erythropoietic protoporphyria or porphyria cutanea tarda, with both forms occurring in 2 patients. Biochemical studies excluded abnormal porphyrin metabolism. PMID- 1895272 TI - Fulminant thrombotic thrombocytopenic purpura in a patient with the limited form of scleroderma: successful outcome using plasma exchange. AB - A 35-year-old woman with a 20-year history of limited scleroderma presented with a 7-day history of low grade fever associated with a red colored urine, 2 days of jaundice and lower extremity petechiae. On admission she had a rapidly deteriorating neurological status associated with thrombocytopenia and microangiopathic anemia. A diagnosis of thrombotic thrombocytopenic purpura (TTP) was made and treatment begun with fresh frozen plasma, plasma exchange and pulse corticosteroids. After a stormy 28-day hospital course she was discharged without residual problems of TTP. PMID- 1895273 TI - Priapism as a manifestation of isolated genital vasculitis. AB - Vasculitis may affect virtually any organ system in the body. We describe a patient who presented with priapism due to isolated genital vasculitis. This responded promptly to oral corticosteroids. In patients presenting with priapism, a possible underlying vasculitis should be considered in the differential diagnosis; the treatment for this may be nonsurgical. PMID- 1895274 TI - Group G streptococcus septic arthritis and osteomyelitis: report and literature review. AB - Beta hemolytic streptococcus group G is increasingly being recognized as a cause of serious infections. We describe a patient with group G streptococcus septic arthritis of the right knee and osteomyelitis of the proximal tibia. Clinical details of 46 patients including 13 patients with infected prosthetic joints reported in the literature were reviewed: 42% had multiple joint involvement. Almost all patients had underlying conditions. Almost one-half were treated with antibiotics alone without therapeutic drainage procedures. Patients with infected prosthetic joints did well without removal of infected prosthesis. There have been 11 cases of group G streptococcus osteomyelitis reported including 3 cases with concomitant septic arthritis. PMID- 1895275 TI - Relapsing polychondritis and Reiter's syndrome. AB - We describe a case of relapsing polychondritis associated with Reiter's Syndrome in a 46-year-old white man. Relapsing polychondritis is a rare disorder of unknown etiology associated in about 30% of cases with other rheumatic disorders such as connective tissue diseases, vasculitis and exceptionally, seronegative spondyloarthritis. We found this association only once in our review of the literature. PMID- 1895276 TI - Primary chest wall tumor appearing as frozen shoulder. Review and case presentations. AB - The term frozen shoulder may apply to a primary, common, recognizable entity with a predictable course to a painful stiff condition with periarthritis secondary to trauma, rotator cuff or arthritic source. We studied 140 cases of frozen shoulder, referred to a surgical clinic for manipulation when conservative care was not effective. Investigations showed only 40 cases had "primary" frozen shoulder and among these were 3 patients with a local primary invasive neoplasm mimicking the exact features of the common condition. The attending physician and surgeon should be suspicious of tumor in younger patients with progressive pain among the other features of primary frozen shoulder. PMID- 1895277 TI - Jaccoud's-type arthropathy: an association with sarcoidosis. AB - We describe a patient with sarcoidosis involving the lungs, muscles and tendons of the forearms who developed Jaccoud's-type arthropathy of the hands. This is the first reported case to the best of our knowledge of sarcoidosis associated with this type of arthropathy. PMID- 1895278 TI - Fever in adult onset Still's disease. Response to methotrexate. AB - Four patients who fulfilled criteria for adult onset Still's disease were treated sequentially with increasing doses of acetylsalicylic acid, nonsteroidal antiinflammatory drugs (NSAID) and prednisone to control their fever and systemic manifestations. Persistence of the fever led us to treat them with small doses of methotrexate (MTX) with excellent response. Low dose MTX should be considered in patients unresponsive to antiinflammatory drugs before using high doses of prednisone. PMID- 1895279 TI - Growth promoting peptides in osteoarthritis: insulin, insulin-like growth factor 1, growth hormone. PMID- 1895280 TI - Immunomodulatory effects of intravenous immunoglobulin G. PMID- 1895281 TI - Evolution of Raynaud's phenomenon to a connective tissue disease. PMID- 1895282 TI - Systemic lupus erythematosus associated with Klinefelter's syndrome--a case report from the USSR. PMID- 1895283 TI - IgA nephropathy and acute interstitial nephritis in a patient with relapsing uveitis and longstanding AS. PMID- 1895284 TI - Penicillamine induced myositis: correlation between urinary zinc excretion and serum creatine. PMID- 1895285 TI - Penicillamine induced lupus-like syndrome in a patient with classical rheumatoid arthritis. PMID- 1895286 TI - Hydralazine induced lupus and Sweet's syndrome. PMID- 1895287 TI - E. B. Hershberg Award Address. My odyssey in drug discovery. PMID- 1895288 TI - New aromatase inhibitors. Synthesis and biological activity of pyridyl substituted tetralone derivatives. AB - The (E)-2-(4-pyridylmethylene)-1-tetralones 1-7 (1, H; 2, 5-OCH3; 3, 6-OCH3; 4, 7 OCH3; 5, 5-OH; 6, 6-OH; 7, 7-OH) were obtained by aldol condensation of the corresponding 1-tetralones with 4-pyridinecarboxaldehyde, and in the case of the OH compounds 5 and 7 subsequent ether cleavage of the OCH3-substituted 2-(4 pyridylmethylene)-1-tetralones. Catalytic hydrogenation of 1-4 gave the 2-(4 pyridylmethyl)-1-tetralones 8-11 (8, H; 9, 5-OCH3; 10, 6-OCH3; 11, 7-OCH3). Subsequent ether cleavage of 9-11 led to the corresponding OH compounds 12-14 (12, 5-OH; 13, 6-OH; 14, 7-OH). The enantiomers of 11 and 12 were separated semipreparatively by HPLC on triacetylcellulose. All compounds (1-14) showed an inhibition of human placental aromatase exhibiting relative potencies from 2.2 to 213 [compounds 6 and (+)-12, respectively; aromatase inhibitory potency of aminoglutethimide (AG) = 1]. The compounds exhibited no or only a weak inhibition of desmolase [cholesterol side chain cleavage enzyme; maximum activity shown by 12, 23% inhibition (25 microM); AG, 53% inhibition (25 microM)]. In vivo, however, the compounds were not superior to AG as far as the reduction of the plasma estradiol concentration and the mammary carcinoma (MC) inhibiting properties are concerned (PMSG-primed SD rats as well as DMBA-induced MC of the SD rat, pre- and postmenopausal experiments, and the transplantable MXT-MC of the BD2F1 mouse). This is due to a fast decrease of the plasma E2 concentration inhibiting effect as could be shown by a kinetic experiment. In addition, select compounds inhibited rat ovarian aromatase much less than human placental aromatase (12, factor of 10). Estrogenic effects as a cause for the poor in vivo activity of the test compounds could be excluded, since they did not show affinity for the estrogen receptor. PMID- 1895289 TI - Design and synthesis of P2-P1'-linked macrocyclic human renin inhibitors. AB - Using a computer model of the active site of human renin developed at Merck, we designed a series of novel P2-P1'-linked, macrocyclic renin inhibitors 3-10. These unique inhibitors incorporate a transition-state isostere within a 13- or 14-membered ring. The three most active compounds in this family were 13-membered ring glutamine-derived inhibitor 3, 14-membered-ring diaminopropionic acid derived inhibitor 6, and 13-membered-ring diol 9 (IC50 0.61, 0.59, 0.65 microM, respectively). Modification of inhibitor 3 at P4 led to 56 nM macrocyclic renin inhibitor 39. This study shows the viability of renin inhibitor designs which incorporate a scissile-bond replacement within a macrocycle. PMID- 1895290 TI - Studies on uricosuric diuretics. 4. Three-dimensional structure-activity relationships and receptor mapping of (aryloxy)acetic acid diuretics. AB - Attempts to develop new (aryloxy)acetic acids with a better profile of diuretic and uricosuric activities as well as with fewer side effects have produced a series of compounds in which the ring system has been varied. Diuretic screening of these analogues in rats indicated that the great difference in the activity between these compounds might be ascribed to a difference in the ring system rather than that in the substituent effect and that the annulation hypothesis described before is not necessarily applicable to all of these compounds. This prompted us to study the relationship between the structure and the diuretic activity of the (aryloxy)acetic acids. An active model (receptor model) was created with the indanone moiety of R-(-)-3 and the dihydrobenzofuran-2 carboxylic acid moiety of S-(+)-4. The three-dimensional structure-activity study of known compounds 2-4, and 5a using the active model showed that the degree of fitting to the model is related to the diuretic activity of these compounds. This was also confirmed for compounds 6a, 6b, 9a, 10a, 11a, 12a, 13a, 14a, 15a, and 16a, and the relation between the structure and the diuretic activity was rationalized qualitatively. With these insights in mind, a modified receptor model was constructed. We believe that this model is useful for a prediction of the activity of compounds not yet synthesized as well as for designing new (aryloxy)acetic acid diuretics. PMID- 1895291 TI - Crystallographic and molecular modeling studies on trypanosomal triosephosphate isomerase: a critical assessment of the predicted and observed structures of the complex with 2-phosphoglycerate. AB - In the continuation of a project aimed at the rational design of drugs against diseases caused by trypanosomes, the crystal structure of trypanosomal triosephosphate isomerase in complex with the active site inhibitor 2 phosphoglycerate has been determined. Two alternative modeling protocols have been attempted to predict the mode of binding of this ligand. In the first protocol, certain key interactions were restrained in the modeling procedure. In the second protocol, a full search of ligand conformational space was performed. In both cases the protein scaffold was kept static. Both protocols produced models which were reasonably close to the observed structure (rms difference less than 2.0 A). Nevertheless, some essential features were missed by each of the protocols. The crystallographic structure of the 2-PGA TIM complex shows that the ligand binds fully within the active site of TIM, with partners for all but one of the ligand's strongly hydrogen bonding groups. Several of the interactions between the ligand and the active site of TIM are seen to be common to all of the complexes so far structurally characterized between trypanosomal triosephosphate isomerase and competitive inhibitors. Such key interactions appear to be the best guide in the prediction of the binding mode of a new inhibitor. PMID- 1895292 TI - Synthesis, ligand binding, QSAR, and CoMFA study of 3 beta-(p-substituted phenyl)tropane-2 beta-carboxylic acid methyl esters. AB - A series of 3 beta-(p-substituted phenyl)tropane-2 beta-carboxylic acid methyl esters (2) were synthesized and found to possess high affinity for the cocaine binding site in rat striatum. The p-chloro (2c) and p-iodo (2n) compounds, which were the most potent analogues prepared, were found to be 85 and 78 times more potent than (-)-cocaine. The p-bromo (2m) and p-methyl (2d) were also 56 and 60 times more potent than cocaine. QSAR and CoMFA studies were conducted to correlate binding affinity of the cocaine analogues with their structural features. Whereas the QSAR study gave relatively low correlations, the CoMFA study gave a correlation with high predictive value. PMID- 1895293 TI - Comparison of azabicyclic esters and oxadiazoles as ligands for the muscarinic receptor. AB - The link between the cognitive deficit associated with Alzheimer type dementia and the loss of cholinergic function in the disease provides a basis for examining muscarinic agonists as potential therapeutic agents. This paper describes the design and synthesis of novel azabicyclic methyl esters as ligands for the muscarinic receptor. Replacement of the methyl ester by a 3-methyl-1,2,4 oxadiazole ring produces potent metabolically more stable muscarinic agonists capable of penetrating the central nervous system. These compounds generally show improved affinity relative to the corresponding methyl esters. 3-Methyl-1,2,4 oxadiazole 7b has an affinity 4 times that of acetylcholine. Receptor affinity is discussed in relation to the size and geometry of the azabicyclic ring and the electronic properties of the heteroaromatic ring. PMID- 1895294 TI - Folate analogues. 35. Synthesis and biological evaluation of 1-deaza, 3-deaza, and bridge-elongated analogues of N10-propargyl-5,8-dideazafolic acid. AB - Structural modifications at the pyrimidine ring and at the C9,N10-bridge region of the thymidylate synthase (TS) inhibitors N10-propargyl-5,8-dideazafolate (1; PDDF; CB 3717), 2-desamino-N10-propargyl-5,8-dideazafolate (2, DPDDF), and 2 desamino-2-methyl-N10-propargyl-5,8-dideazafolate (3, DMPDDF) have been carried out. Methods for the synthesis of 2-desamino-N10-propargyl-1,5,8-trideazafolate (4), 2-desamino-2-methyl-N10-propargyl-3,5,8-trideazafolate (5a), and 2-desamino 2-methyl-N10-propargyl-5,8-dideaza-1,2-dihydrofolate (6) have been developed. The bridge-extended analogues isohomo-PDDF (7) and isohomo-DMPDDF (8) contain an additional methylene group interposed between N10 and the phenyl ring of 1 and 3, respectively. All new compounds were evaluated as inhibitors of TS and the growth of tumor cells in culture. Selected analogues were tested as substrates of folylpolyglutamate synthetase (FPGS) and striking differences in substrate activity were observed among these compounds, indicating that structural modifications at the pyrimidine ring of classical antifolates profoundly influence their polyglutamylation. Enzyme inhibition data established that both N1 and N3-H of the pyrimidine ring are essential for efficient binding of quinazoline-type antifolates to human TS. PMID- 1895295 TI - Structure-activity relationships of estrogenic ligands: synthesis and evaluation of (17 alpha, 20E)- and (17 alpha, 20Z)-21-halo-19-norpregna-1,3,5(10),20 tetraene-3,17 beta-diols. AB - As part our program to probe the molecular requirement for estrogen-receptor binding we undertook the synthesis and evaluation of the 17 alpha,E and 17 alpha,Z halovinyl estradiols. By use of an improved variation of the existing synthetic strategy, the targeted compounds were prepared stereospecifically and in 92-98% yields from the corresponding 17 alpha,E or 17 alpha,Z [(tri-n butylstannyl)vinyl]estradiol 3-acetates. The novel estradiol derivatives were evaluated for their relative binding affinity (RBA) for the estrogen receptor with use of a rat uterine preparation. The results demonstrated a marked difference between the E and Z isomers and among the halogen employed. The Z isomers possessed significantly higher RBA values and the larger halogens (I, Br) were more effective than the smaller Cl substituent. These results modify the previous interpretations of estrogen-receptor binding for steroidal ligands. As a result, our design of (radio)halogenated ligands will incorporate this concern for Z vs E stereochemistry. PMID- 1895296 TI - C-glycosidic analogues of lipid A and lipid X: synthesis and biological activities. AB - The synthesis of a series of novel analogues of lipid A, the lipophilic terminal of lipopolysaccharides (LPS), and lipid X, the reducing monosaccharide unit in lipid A, is reported. In these compounds, the native 1-O-phosphate group has been replaced by a "bioisosteric" CH2COOH substituent. The new N,O-acylated monosaccharide C-glycosides were obtained by Wittig reaction of suitably protected glucosamine derivatives. These lipid X analogues were recognized as substrates by the enzyme lipid A synthase and could be coupled with UDP-lipid X to afford the corresponding disaccharide analogues of the lipid A precursor on preparative scale. All compounds were characterized by NMR, MS, and elemental analysis, and were tested for their ability to enhance nonspecific resistance to infection in mice and also for endotoxicity. The results clearly show that the new compounds express biological activities similar to those of their O phosphorylated natural counterparts. Furthermore, these compounds exhibit a better therapeutic index in mouse models than the standard LPS obtained from Salmonella abortus equi. PMID- 1895298 TI - Synthesis and biological activity of sinefungin analogues. AB - A series of nucleosides (2-4) that derive from adenosine by chain extension at the 5'-end have been synthesized starting from the known phosphonate 7. The latter was first combined with 4-pentenal to give 8, which underwent chemical manipulations to provide triacetate 11, which was found suitable for the adenylation step. Further transformations, among them the Hofmann degradation of the amide group of compound 13, and final deprotection gave nucleosides 2-4. They were considered as analogues of sinefungin (1) and tested for their antileishmanial activity together with compounds 5 and 6, which were obtained independently. All the modifications with respect to sinefungin resulted in nearly complete loss of growth inhibitory activity. These results indicate that the 9' terminal amino and carboxyl groups are necessary for the activity and that the presence of the amino group at C-6' is not sufficient to maintain the antileishmanial effect. Some of the analogues however could antagonize or reverse the inhibitory activity of sinefungin (1). PMID- 1895297 TI - Pregnanes that bind to the digitalis receptor: synthesis of 14-hydroxy-5 beta,14 beta-pregnane glycosides from digitoxin and digitoxigenin. AB - The preparation of the mono-, bis-, and trisdigitoxosides of 14-hydroxy-5 beta,14 beta-pregnan-20-one and 14,20 beta-dihydroxy-5 beta,14 beta-pregnane by two routes, based on the conversion of the alpha,beta-unsaturated gamma-lactone in digitoxin to the 20-ketone and 20 beta-alcohol by ozonolysis and zinc-acetic acid treatment followed by lithium tri-tert-butoxyaluminum hydride reduction, are described. Synthesis of the alpha-L-rhamnoside derivatives is described also. Structures were confirmed by 1H and 13C NMR spectra. These derivatives show strong interaction with the cardiac glycoside receptor of heart muscle in an [3H]ouabain radioligand binding assay. Structure-activity relationships which are reported for glycosides and genins show that the alpha-L-rhamnoside derivatives are more potent than the beta-D-digitoxoside or the beta-D-glucoside and that the beta-D-glucosides are more potent than the mono-, bis-, and trisdigitoxosides. Potency is not increased by the addition of the second and third digitoxose units. PMID- 1895299 TI - Phosphorus-containing inhibitors of HMG-CoA reductase. 2. Synthesis and biological activities of a series of substituted pyridines containing a hydroxyphosphinyl moiety. AB - A series of 2,3,4,(5),6-substituted pyridines containing a hydroxyphosphinyl functionally have been prepared and were evaluated for their ability to inhibit the enzyme HMG-CoA reductase. Systematic substitution of both R1-R4 and X-Y led to compounds of type 3-6 with in vitro potency greater than that of mevinolin (Na salt). PMID- 1895300 TI - Modification of the enkephalin "message" with an artificial polycationic C terminus. AB - The C-terminal "address" sequences of prodynorphin-derived opioid peptides contain an unusually high proportion of basic residues, which are known to be crucial for conferring high activity and selectivity for kappa-opioid receptors. In an effort to investigate the possibility that the polycationic "tails" may be involved in a coulombic interaction with a complementary polyanionic receptor domain, we attached a series of achiral peptide-like cationic fragments to the C terminus of the opioid peptide "message", Tyr-Gly-Gly-Phe. Binding of the various compounds to opioid receptor types in guinea pig brain membranes was weak, and the pharmacologic activities in the guinea pig ileum were marginal. These results indicate either that the chosen ligand design does not satisfy the structural requirements of the hypothesized coulombic interaction or that the latter is a minor criterion governing receptor recognition. PMID- 1895301 TI - Monoterpenic fragment analogues of aplasmomycin as potential antimalarial. AB - Seven analogues of monoterpenic fragment of aplasmomycin were synthesized as targeted antimalarial agents. The potency of the compound 6 was comparable with the sesquiterpene lactone artemisinin and the antibiotic aplasmomycin in vivo against Plasmodium berghei yoelli. PMID- 1895302 TI - Applications of neural networks in quantitative structure-activity relationships of dihydrofolate reductase inhibitors. AB - Back propagation neural networks is a new technology useful for modeling nonlinear functions of several variables. This paper explores their applications in the field of quantitative structure-activity relationships. In particular, their ability to fit biological activity surfaces, predict activity, and determine the "functional forms" of its dependence on physical properties is compared to well-established methods in the field. A dataset of 256 5-phenyl-3,4 diamino-6,6-dimethyldihydrotriazines that inhibit dihydrofolate reductase enzyme is used as a basis for comparison. It is found that neural networks lead to enhanced surface fits and predictions relative to standard regression methods. Moreover, they circumvent the need for ad hoc indicator variables, which account for a significant part of the variance in linear regression models. Additionally, they lead to the elucidation of nonlinear and "cross-products" effects that correspond to trade-offs between physical properties in their effect on biological activity. This is the first demonstration of the latter two findings. On the other hand, due to the complexity of the resulting models, an understanding of the local, but not the global, structure-activity relationships is possible. The latter must await further developments. Furthermore, the longer computational time required to train the networks is somewhat inconveniencing, although not restrictive. PMID- 1895303 TI - Benzylated 1,2,3-triazoles as anticoccidiostats. AB - Substituted 5-amino-4-carbamoyl-1,2,3-triazoles 3a-w were prepared by two synthetic schemes and evaluated in vivo for anticoccidial activity. Both schemes proceeded by brominating appropriately substituted toluenes 4a-s,v to 5a-s,v. In Scheme I, the brominated benzyl analogues 5 were converted to the corresponding benzyl azides 6, which were treated with cyanoacetamide to yield 1-substituted-5 amino-4-carbamoyl-1,2,3-triazoles 3. In Scheme II, the benzyl halides 5 were employed to alkylate the sodium salt of 5-amino-4-carbamoyl-1,2,3-triazole (7). Preliminary screening data against Eimeria acervulina and E. tenella in chickens suggested structural requirements for maximizing activity. Further evaluation against a relatively resistant series of eight Eimeria field isolates revealed L 651,582 (3a) to be a highly effective coccidiostat. However, unacceptable tissue residues precluded further development. Mechanistic studies on this series of 5 amino-4-carbamoyl-1,2,3-triazoles and, in particular, on L-651,582 (3a) revealed that its mode of action does not involve inhibition of IMP dehydrogenase, but probably interferes with host cell calcium entry. In addition, L-651,582 has been found to have antiproliferative activity in several disease models and was recently reported to possess antimetastatic activity in a model of ovarian cancer progression. PMID- 1895304 TI - Potential antitumor agents. 63. Structure-activity relationships for side-chain analogues of the colon 38 active agent 9-oxo-9H-xanthene-4-acetic acid. AB - A series of 16 analogues of the solid tumor active compound 9-oxo-9H-xanthene-4 acetic acid (XAA), with variations in the acetic acid side chain, have been prepared and evaluated for their ability to cause early haemorrhagic necrosis of colon 38 tumors in mice. The results extend the previous SAR for this class and confirm the necessity for a carboxylic acid group in a fixed disposition with respect to the xanthenone chromophore. None of the compounds showed superior potency to XAA itself, with virtually all alterations in the nature of the anionic center or its geometry with respect to the chromophore greatly reducing or abolishing activity. However, alpha-methylation of the side chain was permissible, and the two enantiomers of 5-methyl-alpha-methyl-XAA were separated and tested. Both were active, but the S-(+) enantiomer was much more dose-potent than the R-(-) enantiomer, in both the in vivo tumor necrosis assay and an in vitro assay measuring the stimulation of nitric oxide production by macrophages. This suggests that the enantiomers have different intrinsic activities, rather than differing in their vivo metabolism. PMID- 1895305 TI - N6,9-disubstituted adenines: potent, selective antagonists at the A1 adenosine receptor. AB - N6-Substituted 9-methyladenines are potent antagonists of the activation of A1 adenosine receptors. The present study assessed the effect of N6 and N-9 substituents on the binding of adenines to the A1 and A2 receptors, respectively, of rat brain cortex and striatum and also on the antagonism of the A2 receptor mediated stimulation of the adenylate cyclase of PC12 cells by N-ethyladenosine 5'-uronamide. The potency ranking of 9-substituted adenines varied directly with the hydrophobicity of the substituent: cyclopentyl greater than phenyl greater than tetrahydrofuryl greater than ethyl greater than methyl greater than 2 hydroxyethyl. The 9-substituted adenines showed little selectivity for either receptor and the R enantiomer of N6-(1-phenyl-2-propyl)-9-methyladenine was only 4-fold more potent than the S enantiomer at the A1 receptor. An N6-cyclopentyl substituent increased potency at the A1 receptor and decreased potency at the A2 receptor, resulting in selectivity for the A1 receptor of up to 39-fold. The N6 cyclopentyl group completely overshadowed the effect of the hydrophobicity of the 9-substituent. A 2-chloro substituent did not alter the potency of an N6 substituted 9-methyladenine. PMID- 1895306 TI - Synthesis and adenosine receptor affinity of a series of pyrazolo[3,4 d]pyrimidine analogues of 1-methylisoguanosine. AB - Pyrazolo[3,4-d]pyrimidines are pyrazolo analogues of purines. They have been shown to be a general class of compounds which exhibit A1 adenosine receptor affinity. Two series of pyrazolo[3,4-d]pyrimidine analogues of 1 methylisoguanosine have been synthesized. The first involved substitution of the N1-position while the second involved substitution of the N5-position. Both alkyl and aryl substituents were examined. All compounds were tested for A1 adenosine receptor affinity by using a (R)-[3H]-N6-(phenylisopropyl)adenosine binding assay. The 3-chlorophenyl group showed the greatest activity in the N1-position and the butyl group produced the greatest activity in the N5-position. Combination of the best substituent in each of these positions enhanced the overall activity. The most potent compound was 4-amino-5-N-butyl-1-(3 chlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-6(5H)- one with an IC50 of 6.4 x 10(-6) M. Selectivity at the receptor subclasses was examined by performing an A2 adenosine receptor affinity assay with [3H]CGS 21680. This series of compounds were slightly less potent at A2 receptors. 4-Amino-5-N-butyl-1-(3-chlorophenyl-1H pyrazolo[3,4-d]pyrimidin-6(5H)-one was the most potent compound with an IC50 of 19.2 x 10(-6) M. PMID- 1895307 TI - Nucleosides and nucleotides. 100. 2'-C-cyano-2'-deoxy-1-beta-D-arabinofuranosyl cytosine (CNDAC): design of a potential mechanism-based DNA-strand-breaking antineoplastic nucleoside. PMID- 1895308 TI - Potent, orally active imidazo[4,5-b]pyridine-based angiotensin II receptor antagonists. PMID- 1895309 TI - Substituted 2-(aminomethyl)piperidines: a novel class of selective protein kinase C inhibitors. PMID- 1895310 TI - A selective, reversible, competitive inhibitor of monoamine oxidase A containing no nitrogen, with negligible potentiation of tyramine-induced blood pressure rise. PMID- 1895311 TI - Nitroheterocycle reduction as a paradigm for intramolecular catalysis of drug delivery to hypoxic cells. PMID- 1895313 TI - Von Hippel-Lindau disease: a genetic study. AB - Genetic aspects of von Hippel-Lindau (VHL) disease were studied in familial and isolated cases. Complex segregation analysis with pointers was performed in 38 kindreds with two or more affected members. Dominant inheritance with almost complete penetrance in the highest age classes (0.96 at 51 to 60 and 0.99 at 61 to 70 years) was confirmed and there was no evidence of heterogeneity between families ascertained through complete and incomplete selection. The point prevalence of heterozygotes in East Anglia was 1.89/100,000 (1/53,000) persons with an estimated birth incidence of 2.73/100,000 (1/36,000) live births. Reproductive fitness was 0.83. Direct and indirect estimates of the mutation rate were 4.4 (95% CI 0.9 to 7.9) x 10(-6)/gene/generation and 2.32 x 10( 6)/gene/generation respectively. There was no significant association between parental age or birth order and new mutations for VHL disease. PMID- 1895312 TI - Osteogenesis imperfecta: translation of mutation to phenotype. PMID- 1895314 TI - Predictive diagnosis of myotonic dystrophy with flanking microsatellite markers. AB - Linkage was shown between the myotonic dystrophy locus (DM) and a highly polymorphic AC repeat marker within the kallikrein (KLK1) locus (Z = 3.00, theta = 0.0). Linkage between KLK1 and the highly polymorphic AC repeat marker within the apolipoprotein C2 (APOC2) locus, which had been established in normal families, was confirmed in myotonic dystrophy families (Z = 4.37, theta = 0.11). These highly polymorphic AC repeat markers flank DM on chromosome 19. The gene order is cen-APOC2 (0.03) DM (0.08) KLK1-qter with recombination frequencies shown in parentheses. Genotypes for the AC repeat markers can be determined simultaneously by multiplex PCR and separation of the two base pair differences between adjacent alleles on sequencing gels. In informative families, this approach provides rapid diagnosis and is more accurate than methods using markers restricted to the proximal side of the myotonic dystrophy gene. PMID- 1895315 TI - Genetic localisation of the RP2 type of X linked retinitis pigmentosa in a large kindred. AB - Genetic linkage and deletion studies have led to the proposal that there are at least two loci on the X chromosome which are responsible for X linked retinitis pigmentosa (XLRP). One locus (RP3) has been closely defined by genetic linkage and deletion analyses and localised to the region between the ornithine transcarbamylase (OTC) and chronic granulomatous disease (CYBB) loci in Xp21.1 p11.4. The other locus (RP2) has been assigned by linkage analysis alone to region Xp11.4-p11.2, but its localisation is less well defined. The results of a multipoint linkage analysis of a single large XLRP kindred using eight informative loci provide further evidence on the localisation of RP2 to this region. The maximum likelihood location of this locus shows a multipoint lod score of 7.17 close to DXS255 (in Xp11.22) and TIMP (in Xp11.3-p11.23), neither of which show recombination with RP2, in an area extending from 2 cM proximal to DXS7 to 1 cM distal to DXS14 (approximate 95% confidence limits). PMID- 1895317 TI - Application of D'Arcy Thompson's coordinate transformation approach to clinical genetics photographs using image processing techniques. AB - The coordinate transformation approach outlined by D'Arcy Thompson for analysing biological shape was extended using modern computerised image processing techniques so that it could be applied to photographs for the study of patients with syndromes of altered facial morphogenesis. Photographs digitised at a resolution of 512 by 480 pixels were subjected to 'rubbersheeting' transformations using a fast microcomputer. Starting with a photograph of a normal child, a single application of the rubbersheeting algorithm produced features such as an upturned nose quite simply. Other facial anomalies may also be recreated with multiple applications. Preliminary results suggest that this technique may be a useful tool in attempts to understand and analyse the changes in facial configuration in a variety of syndromes with facial anomalies. PMID- 1895316 TI - Characterisation of a glycine to valine substitution at amino acid position 910 of the triple helical region of type III collagen in a patient with Ehlers-Danlos syndrome type IV. AB - We have studied a patient with Ehlers-Danlos syndrome type IV. Protein mapping studies of her type III collagen had indicated that cyanogen bromide fragment 9 contained the site of the mutation. Here we describe the mapping of this region for a single base mutation using a chemical modification and cleavage technique. Sequence analysis of cDNA showed a G to T mutation resulting in the substitution of glycine 910 by valine. This was confirmed by allele specific oligonucleotide hybridisation to the proband's genomic DNA. PMID- 1895318 TI - A rare heteromorphism of chromosome 20 and reproductive loss. AB - A rare centromeric heterochromatic variant of chromosome 20 was encountered during investigations in a couple with repeated miscarriages. The enlarged segment was G and C band positive and stained positively by Giemsa II. In situ hybridisation of the biotinylated alphoid probe D20Z1 specific for the centromere of chromosome 20 to metaphase cells confirmed the presence of amplified sequences adjacent to the centromere. The variant was found to be familial and was evaluated as having no clinical significance. PMID- 1895319 TI - Bilateral split hand and split foot malformation in a boy with a de novo interstitial deletion of 7q21.3. PMID- 1895320 TI - Genochondromatosis. AB - We report a new disorder that we have called genochondromatosis. Four patients from the same family with the characteristic localisation of chondromatosis (clavicle, upper end of humerus, and lower end of femur) were investigated. The favourable course, the dominant transmission, and previous publication of similar cases confirm the uniqueness of this new entity. The chondrodysplasias with disorganised development of cartilage are far from being completely understood. Recently, several disorders within this group have been well defined, including metachondromatosis and spondyloenchondroplasia, but there still remain numerous clinical subgroups that are very difficult to classify. PMID- 1895321 TI - Hypoglossia-hypodactyly syndrome with hydrocephalus: a clue to the aetiology? AB - A stillborn female with Hanhart's syndrome in association with hydrocephalus owing to stenosis of the aqueduct of Sylvius is presented. Neuropathological findings are suggestive of an acquired pathophysiological mechanism. PMID- 1895322 TI - Familial occurrence of tumours of the choroid plexus. AB - The case histories of two children of consanguineous parents with papillomas of the choroid plexus are presented. Although exogenic factors in the genesis of these neoplasms can not be excluded, autosomal recessive inheritance is proposed. PMID- 1895323 TI - Triphalangeal thumb with delta phalanx in a case of Klinefelter's syndrome. AB - We report a case of Klinefelter's syndrome owing to maternal meiotic error associated with triphalangeal thumb and delta phalanx bilaterally. There are no previous reports of similar cases and triphalangism with delta phalanx abnormalities of both thumbs might therefore be considered a further, but rare, manifestation of this aneuploidy. PMID- 1895324 TI - Rat model of chronic lung infections caused by non-typable Haemophilus influenzae. AB - Patients with chronic obstructive pulmonary disease (COPD) often have chronic or recurrent pulmonary infections with non-typable Haemophilus influenzae. A model of these infections exploited agar bead vehicles to protect the inoculum from rapid clearance, and a chronic lung infection of at least 42 days duration was established in rats. This infection induced increases in serum IgG titres to outer-membrane (OM) and lipo-oligosaccharide (LOS) antigens; immunoblotting demonstrated that this humoral response was directed partly against the outer membrane proteins (OMPs). Lung lavage fluid also contained an increased titre of IgG antibodies to OM and LOS 42 days after infection. Antibodies produced during infection with one strain of H. influenzae cross-reacted with OMPs from another, non-typable H. influenzae strain. Despite their encasement in agar beads, pulmonary H. influenzae remained susceptible to amoxycillin. This model of chronic pulmonary infections due to non-typable H. influenzae appears to resemble the situation in COPD patients and may be useful for experimental therapeutic studies. PMID- 1895325 TI - Biochemical properties of group G streptococci isolated from cats and man. AB - The biochemical characteristics of group G streptococci isolated from cats were markedly similar to the characteristics of group G streptococci from man. Both cat and human isolates of group G streptococci were also very similar in biochemical characteristics to group A streptococci so that to identify the source of group G streptococci by biochemical reactions is not a reliable procedure. The group G streptococci found in many cats could be pathogenic to man, since their physiological and biological characteristics are very similar to those of group A streptococci. PMID- 1895326 TI - Comparison of a DNA probe assay with culture for the detection of Chlamydia trachomatis. AB - A new DNA probe assay (PACE 2, Gen-probe) was compared with cell culture for the detection of Chlamydia trachomatis in 909 women attending the Royal Women's Hospital, Melbourne, Victoria. The DNA probe assay had a sensitivity of 86.2%, a specificity of 99.9% and a positive predictive value of 96.2% in a population with 3.2% prevalence, indicating that it may be a suitable alternative to culture for the detection of C. trachomatis in specimens from the genital tract. PMID- 1895327 TI - Enterotoxigenic Escherichia coli associated with infant diarrhoea in Galicia, north-western Spain. AB - To assess the role of enterotoxigenic Escherichia coli (ETEC) in infantile diarrhoea, 482 children with diarrhoea and 103 healthy controls, from three localities of Galicia, north-western Spain, were investigated between 1985 and 1988. Rotavirus (37.3%) and Salmonella spp. (12.8%) were the most common causal agents, followed by ETEC (3.9%), Campylobacter jejuni (2.3%), Shigella spp. (0.9%) and Yersinia enterocolitica (0.5%). ETEC were significantly more frequently isolated from children with diarrhoea who were under 1 month of age (26.5%) than from older diarrhoeic children (2.2%) (p less than 0.001) or from healthy children who were under 1 month of age (0%) (p less than 0.05). Among children who harboured ETEC, five of the nine children under 1 month of age developed diarrhoea in hospital, whereas none of the 10 children over 1 month of age did so. Seventeen ETEC isolates produced heat-stable enterotoxin (STa) only, four produced only heat-labile enterotoxin (LT), and two produced both toxins. Colonisation factor antigens CFA/I and CFA/II were detected in 11 (55.0%) of the 20 ETEC isolates that remained enterotoxigenic after maintenance in the laboratory. Most ETEC isolates belonged to serotypes O153:K-:H45 (nine STa+ CFA/I+ isolates), O27:K-:H7 (three STa+ isolates) or O6:K15:H16 (two LT+ STa+ CFA/II+ isolates). Our results suggest that ETEC constitute an important cause of neonatal diarrhoea in this part of Spain. PMID- 1895328 TI - Use of a grooming and foraging substrate to reduce cage stereotypies in macaques. AB - We examined the effects of a synthetic fleece pad on cage stereotypies in individually housed cynomolgus monkeys. Animals which received the fleece alone engaged in grooming which was associated with an increase in time spent resting. Monkeys given fleece pads sprinkled with morsels of food did not groom the fleece, but rather foraged for long periods (up to 27 min/h). Stereotyped behaviours were reduced by up to 73% by use of the fleece pad both alone and with foraging crumbles. PMID- 1895329 TI - The macaque model for in vitro fertilization: superovulation techniques and ultrasound-guided follicular aspiration. AB - Prior methods for macaque in vitro fertilization (IVF) have incorporated laparoscopy and/or laparotomy as the primary means for oocyte recovery. Sonographic techniques, as used with human IVF, have been applied to the macaque, both for monitoring the response to hyperstimulation and for follicular aspiration prior to ovulation. Pergonal (hMG) was administered for 7 or 8 days beginning on cycle day 1 or 2 or for 6 days beginning on cycle day 3. This was followed by Pregnyl (hCG) prior to follicular aspiration. The quality of oocytes recovered from the 6-day treatment group was considerably better than those treated for greater than or equal to 7 days. It was concluded that ultrasound can provide a reliable means for documenting the response to ovarian stimulation and the successful transabdominal aspiration of multiple follicles. PMID- 1895330 TI - Hematology, serum chemistry values, and rectal temperatures of adult greater galagos (Galago garnetti and G. crassicaudatus). AB - Hematological and serum chemistry values, as well as rectal temperatures, were obtained from greater galagos (Galago garnettii and G. crassicaudatus), in order to establish normative values. No species or sex differences were found for four hematological parameters and 15 serum chemistry parameters. Species differences were seen in phosphate, magnesium, cholesterol, alkaline phosphate, G-glutamyl transferase, mean corpuscular volume and leucocyte, neutrophil, and lymphocyte number. Significant sex differences were observed in glucose, hemoglobin, and hematocrit values. Species and sex differences were seen in chloride and erythrocyte number. PMID- 1895331 TI - The use of nonmetal electrodes in electroejaculation of restrained but unanesthetized macaques. AB - A successful technique for electroejaculation with nonmetallic electrodes cut from defibrillation pads is described. Twenty-six adult male cynomolgus and eleven adult male rhesus macaques were electroejaculated while immobilized with chair restraint. From 123 attempted electroejaculations in both species of macaques, 119 semen specimens were obtained. The volume, concentration, % motility, and % normal forms of cynomolgus and rhesus macaque semen are presented. The use of nonmetallic electrodes provides a high quality ejaculate while minimizing the risks of adverse affects on valuable populations of macaques. PMID- 1895332 TI - Genetic polymorphism of the vitamin D-binding protein (DBP) in crab-eating macaques (Macaca fascicularis). AB - Vitamin D-binding protein (DBP) of crab-eating macaques (Macaca fascicularis) was examined by means of three electrophoretic methods. DBP phenotypes were observed to be one or two bands in each method. All of DBP molecular variants could be detected by the simultaneous typing with these three methods. Family analysis suggested that DBP variants followed the mode of autosomal codominant inheritance. A total of 17 phenotypes governed by at least 11 alleles were observed in the populations of Malaysia, Indonesia, and the Philippines. The genetic variability was high in Malaysian and Indonesian populations but low in the Philippine population. PMID- 1895333 TI - Battelle Primate Facility. AB - The Battelle Primate Facility houses one of the largest collections of neotropical primates in the United States. The facility is a research resource for undergraduate and graduate students. Battelle staff, as well as staff and faculty from U.S. and international institutions. Researchers have access to the animals for a variety of studies encompassing several disciplines, a large collection of preserved tissues, and an extensive biomedical database. The facility is a World Health Organization Collaborative Center for Clinical Pathology of Neotropical Primates and is involved with the Peruvian Primatological Project in Iquitos, Peru, which provides opportunities for research in primatology and conservation. PMID- 1895334 TI - Deciduous dentition eruption sequence of the laboratory-reared chimpanzee (Pan troglodytes). AB - Eruption sequence and age ranges for the maxillary and mandibular deciduous dentition were generated from serial dental study models from 28 laboratory reared chimpanzees (Pan troglodytes). These data can serve as additional normative, baseline information for the evaluation of fetal insults on neonatal growth and development in the laboratory-reared chimpanzee. PMID- 1895335 TI - Presence of adult or juvenile relatives increases livebirth chances in captive stumptail macaques (Macaca arctoides). PMID- 1895336 TI - Endogenous bilirubin excretion in Bolivian squirrel monkeys with a Gilbert's-like syndrome. AB - Fasted Bolivian squirrel monkeys (BoSM) exhibit a marked hyperbilirubinemia when compared to fed BoSM. This fasting hyperbilirubinemia (FH) is similar to that in human patients with Gilbert's syndrome. Endogenous bilirubin (BR) excretion (production) into bile was elevated two-fold in BoSM upon fasting. The fraction of injected dose of 3 H-amino-levulinic acid (ALA) incorporated into biliary BR in fasted monkeys was of less magnitude than in fed monkeys and was associated with lower specific activities of 3 H-BR. Both the lower incorporation of ALA and lower specific activities of 3H-BR in fasted BoSM suggest that increased BR excreted may have arisen from pre-existing non-labeled pools of either heme or BR. PMID- 1895337 TI - Fast sampling, rapid filtration apparatus: principal characteristics and validation from studies of D-glucose transport in human jejunal brush-border membrane vesicles. AB - Kinetic data in (brush-border) membrane vesicles which rely on the validity of the initial rate assumption for their interpretation and depend on tracer flux studies using the rapid filtration technique for their experimental measurement have been limited to some extent by the absence of techniques that would allow for real-time data analysis. In this paper, we report on our successful design of a fast sampling, rapid filtration apparatus (FSRFA) which seems to fill up this technical gap since showing the following characteristics: (i) rapid injection (5 msec) and mixing (less than 100 msec) of small amounts of vesicles (10-40 microliters) with an incubation medium (0.2-1.0 ml); (ii) fast (20 to 80 msec depending on the sample volume) and multiple (up to 18 samples at a maximal rate of 4 sec) sampling of the uptake mixture followed by rapid quenching in the stop solution (approximately 5 msec) according to a predetermined time schedule (any time combination from 0.25 to 9999 sec); and (iii) fast, automated, and sampling synchronized filtration and washings of the quenched uptake medium (only 15-20 sec are necessary for the first filtration followed by two washings and extra filtrations). As demonstrated using adult human jejunal brush-border membrane vesicles and Na(+)-D-glucose cotransport as models, the FSRFA accurately reproduces the manual aspects of the rapid filtration technique while allowing for very precise initial rate determinations. Moreover, the FSRFA has also been designed to provide as much versatility as possible and, in its present version, allows for a very precise control of the incubation temperature and also permits a few efflux protocols to be performed. Finally, its modular design, which separates the fast sampling unit from the rapid filtration device, should help in extending its use to fields other than transport measurement. PMID- 1895338 TI - Analysis of kinetic data in transport studies: new insights from kinetic studies of Na(+)-D-glucose cotransport in human intestinal brush-border membrane vesicles using a fast sampling, rapid filtration apparatus. AB - Using the fast sampling, rapid filtration apparatus (FSRFA) recently developed in our laboratory (Berteloot et al., 1991, J. Membrane Biol. 122:111-125), we have studied the kinetic characteristics of Na(+)-D-glucose cotransport in brush border membrane vesicles isolated from normal adult human jejunum. True initial rates of transport have been determined at both 20 and 35 degrees C using a dynamic approach which involves linear-regression analysis over nine time points equally spaced over 4.5 or 2.7 sec, respectively. When the tracer rate of transport was studied as a function of unlabeled substrate concentrations added to the incubation medium, a displacement curve was generated which can be analyzed by nonlinear regression using equations which take into account the competitive inhibition of tracer flux by unlabeled substrate. This approach was made imperative since at 20 degrees C, in the presence of high substrate concentrations or 1 mM phlorizin, no measurable diffusion was found and the resultant zero slope values cannot be expressed into a classical v versus S plot. All together, our results support the existence of a single Na(+)-D-glucose cotransport system in these membranes for which Na+ is mandatory for uptake. This conclusion is at variance with that of a recent report using the same preparation (Harig et al., 1989. Am J. Physiol. 256:8618-8623). Since the discrepancy seems difficult to resolve on the consideration of experimental conditions alone, we have determined the kinetic parameters of D-glucose transport using one time point measurements and linear transformations of the Michaelis-Menten equation, in order to investigate the potential problems of such a widely used procedure. Comparing these approaches, we conclude that: (i) the dynamic uptake measurements give a better understanding of the different uptake components involved: (ii) it does not matter whether a dynamic or a one time point approach is chosen to generate the uptake data provided that a nonlinear-regression analysis with proper weighting of the data points is performed; (iii) analytical procedures which rely on linearization of Michaelian process(es) are endowed with a number of difficulties which make them unsuitable to resolve multicomponent systems in transport studies. A more general procedure which uses a nonlinear-regression analysis and a displacement curve is proposed since we demonstrate that it is far superior in terms of rapidity, data interpretation, and visual information. PMID- 1895340 TI - Communication. PMID- 1895341 TI - Stigma and blindness. AB - Moral disapproval, denigration, and avoidance are part of the stigma toward persons with blindness, as well as other chronic diseases. This stigma can affect adjustment, leading to decreased social and self-acceptance. Health-care professionals share the value and beliefs of society, and by their actions may contribute to the discrediting of the individual. Strategies can be used to increase awareness of the attitudes that health-care professionals hold, as well as assisting blind persons to manage their stigma. PMID- 1895339 TI - Muscarinic responses of gastric parietal cells. AB - Isolated rabbit gastric glands were used to study the nature of the muscarinic cholinergic responses of parietal cells. Carbachol (CCh, 100 microM) stimulation of acid secretion, as measured by the accumulation of aminopyrine, was inhibited by the M1 antagonist, pirenzepine, with an IC50 of 13 microM; by the M2 antagonist, 11,2-(diethylamino)methyl-1 piperidinyl acetyl-5,11-dihydro-6H-pyrido 2,3-b 1,4 benzodiazepin-6-one (AF-DX 116), with an IC50 of 110 microM; and by the M1/M3 antagonist, diphenyl-acetoxy-4-methylpiperidinemethiodide (4-DAMP), with an IC50 of 35 nM. The three antagonists displayed equivalent IC50 values for the inhibition of carbachol-stimulated production of 14CO2 from radiolabeled glucose, which is a measure of the turnover of the H,K-ATPase, the final step of acid secretion. Intracellular calcium levels were measured in gastric glands loaded with FURA 2. Carbachol was shown to both release calcium from an intracellular pool and to promote calcium entry across the plasma membrane. The calcium entry was inhibitable by 20 microM La3+. The relative potency of the three muscarinic antagonists for inhibition of calcium entry was essentially the same as for inhibition of acid secretion or pump related glucose oxidation. Image analysis of the glands showed the effects of carbachol, and of the antagonists, on intracellular calcium were occurring largely in the parietal cell. The rise in cell calcium due to release of calcium from intracellular stores was inhibited by 4-DAMP with an IC50 of 1.7 nM, suggesting that the release pathway was regulated by a low affinity M3 muscarinic receptor or state; Ca entry and acid secretion are regulated by a high affinity M3 muscarinic receptor or state, inhibited by higher 4-DAMP concentrations (greater than 30 nM), suggesting that it is the steady-state elevation of Ca that is related to parietal cell function rather than the [Ca]i transient. Displacement of 3H N-methyl scopolamine (NMS) binding to purified parietal cells by CCh showed the presence of two affinities for CCh, but only a single affinity for 4-DAMP and lower affinity for pirenzepine and AFDX 116, providing further evidence for the parietal cell location of the [Ca]i response. Elevation of steady-state [Ca]i levels with either ionomycin or arachidonic acid did not replicate M3 stimulation of acid secretion or glucose oxidation, hence elevation of [Ca]i is necessary but not sufficient for acid secretion. PMID- 1895342 TI - Treatment of persistent hyperplastic primary vitreous. AB - Persistent hyperplastic primary vitreous (PHPV) will usually lead to a cataract and secondary glaucoma if not treated. At least a lensectomy should be performed to reduce the frequent incidence of glaucoma. In the purely anterior form, the cataract should be removed as well as the PHPV, as this gives a clear media that can be rehabilitated visually. Eyes with a posterior PHPV have poor visual results due to posterior pole abnormalities. PMID- 1895343 TI - A fail-safe system for ophthalmic group practice. AB - If a mistake is made by a staff member, the error is detected and corrected automatically by other staff members before the patient is affected. In employing the Fail-Safe System, all personnel must accept that mistakes are inevitable but can be kept to a minimum through staff cooperation. The two key points of the Fail-Safe System are the correct receipt and transmission of information and, once the information is received, the ability of the receiver to assess the correctness of the information. The five subsystems of the Fail-Safe System are the improvement of each employee's medical knowledge; the mastering of correct pronunciation; the mastering of correct writing; the maintenance of a constructive atmosphere in the hospital; and a trouble reporting and analysis process. PMID- 1895344 TI - Retinopathy of prematurity. AB - Retinopathy of prematurity (ROP) is a bilateral retinal disease found in premature infants born at less than 36 weeks gestation or weighing less than 1,600 g. Several recent studies have suggested a multifactorial basis for ROP development. Risk factors include apnea treated by mask or bag ventilation, repeated blood transfusions, prolonged parenteral nutrition, hypoxemia, hypercarbia, hypocarbia, and supplemental oxygen administration. Disease stages are: stage 1--demarcation line; stage 2--intraretinal ridge; stage 3--ridge plus extraretinal fibrovascular proliferation; and stage 5--total retinal detachment. PMID- 1895345 TI - The first assistant's role in managing phacoemulsification complications. AB - Every surgeon who performs phacoemulsification will encounter complications. Successful management of complications is enhanced by a combination of surgical skill, good judgment, and a well-trained, highly motivated first assistant. The first assistant must have already mastered the names and uses of all instruments and equipment, and will have practiced the eye/hand coordination necessary to work comfortably with microscopes and loupes. A positive attitude and total concentration on the procedure and the surgeon is imperative. A complete understanding of the management of the most common complications will enable the assistant to begin setting the stage to manage a complication during the anticipatory phase. PMID- 1895346 TI - Update on contact lens solutions. PMID- 1895347 TI - LifeSight: growing older with good vision. PMID- 1895348 TI - Oxygen dependence of lipid peroxidation in mice. AB - Peroxidation of lipids in serum and tissues of mice placed in low or high levels of oxygen was examined. After exposure to 100% oxygen for 3 h, no significant differences were observed between control and exposed mice. However, exposure to 100% oxygen for 6 h resulted in a decrease in oxygen consumption, an increase in lipid peroxides in tissues and serum, and the formation of hydroxyl radicals in tissues and serum. At low concentrations of oxygen (14% or 16%), a decrease in oxygen consumption, peroxidation of lipids and formation of hydroxyl radicals also were observed. Damage to mice was great with the lower oxygen concentrations of oxygen. There was a close correlation between the consumption of oxygen lipid peroxidation, formation of hydroxyl radicals. PMID- 1895349 TI - Protective effect of taurine against acute paraquat intoxication in rats. AB - The effect of taurine (TA) on acute paraquat (PQ) intoxication was investigated in rats. Treatment with TA was begun 10 min after rats received a s. c. injection of PQ 40 mg/kg. Saline (0.9%) or 5% TA solution were infused i.v. for 5-6 min (short-interval infusion study). One hour after TA infusion, PQ concentration in the blood was increased and that in the urine was lowered, as compared with those in the saline-infused group. Significant increases of the PQ concentration was observed in kidney at 3 hours after TA administration. Excreted urine volume was significantly higher in the TA group during the time-period of 0-1 and 0-5 hours after the 5% TA administration compared with that of the saline group. However, there were no significant differences in total urinary PQ excretion between the two groups. Saline or 2.5% and 5% TA was infused continuously during the time period of 0-1, 0-3 or 0-5 hours (long-interval infusion study). A marked increase in PQ concentration in blood and a reduction of PQ concentration in kidney were noticed during the time-period of 1-5 hours after the 5%TA infusion. Urinary excretion was remarkably accelerated by 5% TA infusion and the total urine volume increased to 20 times during the time-period 0-1 hour and 1.7 times during the time-period of 3-5 hours as compared with the saline control. In addition, urinary volume during the time-period of 0-5 hours almost reached that of 5% TA volume which infused to animals. The mortality rate of the groups that received either single or double short-time infusion of 5% TA was 100%. Thus, these results suggest that a long continuous infusion of 5% TA increased urine output and inhibits of PQ accumulation in renal tissue despite a rise in blood PQ concentration. PMID- 1895350 TI - Four-week sub-acute toxicity study of S-(-)-9-fluoro-2,3-dihydro-3-methyl-10- (4 methyl-1-piperazinyl)-7-oxo-7H-pyrido-[1,2,3,-de] [1,4]benzoxazine-6- carboxylic acid hemihydrate (DR-3355) in CD rats and cynomolgus monkeys. AB - S-(-)-9-Fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H -pyrido [1,2,3,-de] [1,4]benzoxazine-6-carboxylic acid hemihydrate, DR-3355, a new quinolone antimicrobial agent, was administered by oral gavage to groups of ten male and ten female CD rats at dosages of 50, 200 or 800 mg/kg/day and to groups of three male and three female cynomolgus monkeys at dosages of 10, 30, or 100 mg/kg/day. Both species were treated for four weeks. The vehicle (0.5% sodium carboxymethyl cellulose)-treated group served as control. Rats at the high dose showed salivation, slight increases in total leucocyte and lymphocyte counts, slight changes in the plasma electrolyte balance, and minor reductions in urea concentration. The articular surfaces of the humerus and femur of rats at the high dose showed minor degenerative changes. Increased caecal weight occurred in rats at all the treatment groups. Monkeys at the high dose showed salivation, diarrhoea and lost weight. There was no microscopic change in the tissues examined. No effect levels under these conditions were established at 200 mg/kg/day in the rat, and 30 mg/kg/day in the monkey. PMID- 1895351 TI - Comparison of body composition and somatotype of trained female triathletes. AB - The body composition and somatotype of 16 trained female triathletes aged 18.8 32.8 years were measured. All of the subjects were engaged in a competitive training programme and participated in the same triathlon. Anthropometric variables included height, mass, selected diameters, girths and skinfolds, and a Heath-Carter anthropometric somatotype. Body composition was determined by hydrostatic weighing procedures and skinfold patterns. Comparisons were made with Olympic swimmers and runners. The triathletes had a mean body mass of 55.2 kg and a mean height of 162.1 cm. When compared to swimmers, the triathletes were somewhat shorter and significantly (P less than 0.005) older. On most other measures, including a balanced mesomorph somatotype of 3.1-4.3-2.6, they were similar to swimmers. This group of triathletes were generally heavier, less lean, more mesomorphic and less ectomorphic than elite runners. Reported body densities from other studies indicated little difference between the triathletes and other groups. Skinfold patterns were similar in shape for all groups, but the runners had smaller values, at all sites, than either swimmers or triathletes. Because of lack of information on cyclists, adequate comparisons were not possible. Regression analysis indicated that training parameters were more important than anthropometric measures in the prediction of performance. It was concluded that this group of triathletes were closer, with respect to both body composition and somatotype, to swimmers than to runners. PMID- 1895352 TI - Biomechanics of stair walking and jumping. AB - Physical activities such as stair walking and jumping result in increased dynamic loading on the human musculoskeletal system. Use of light weight, externally attached accelerometers allows for in-vivo monitoring of the shock waves invading the human musculoskeletal system during those activities. Shock waves were measured in four subjects performing stair walking up and down, jumping in place and jumping off a fixed elevation. The results obtained show that walking down a staircase induced shock waves with amplitude of 130% of that observed in walking up stairs and 250% of the shock waves experienced in level gait. The jumping test revealed levels of the shock waves nearly eight times higher than that in level walking. It was also shown that the shock waves invading the human musculoskeletal system may be generated not only by the heel strike, but also by the metatarsal strike. To moderate the risk of degenerative joint disorders four types of viscoelastic insoles were utilized to reduce the impact generated shock waves. The insoles investigated were able to reduce the amplitude of the shock wave by between 9% and 41% depending on the insole type and particular physical activity. The insoles were more effective in the reduction of the heel strike impacts than in the reduction of the metatarsal strike impacts. In all instances, the shock attenuation capacities of the insoles tested were greater in the jumping trials than in the stair walking studies. The insoles were ranked in three groups on the basis of their shock absorbing capacity. PMID- 1895353 TI - Relationships between muscle fibre characteristics and physical performance capacity in trained athletic boys. AB - The relationships between muscle fibre characteristics and the physical performance capacity of trained athletic boys (aged 11-13 years) were studied over 2 days. The subjects were divided into two groups according to muscle fibre distribution. The 'fast' group (FG) comprised 10 subjects (sprinters, weightlifters, tennis players) with more than 50% fast-twitch fibres (type II), and the 'slow' group (SG) comprised 8 subjects (endurance runners, tennis players, one weightlifter) with more than 50% slow-twitch fibres (type I) in their vastus lateralis muscle. The 'fast' group had 59.2 +/- 6.3% and the 'slow' group had 39.4 +/- 9.8% type II fibres. Other clear differences (P less than 0.05 0.01) between the groups were observed as regards reaction time, rate of force development and rise of the body's centre of gravity in the squatting jump. For these variables, the 'fast' group was superior to the 'slow' group. Muscle fibre distribution (% type II) correlated (P less than 0.05-0.01) negatively with reaction time. Muscle fibre area (% type II) correlated negatively with reaction time (P less than 0.05-0.001) and positively with chronological age (P less than 0.05) height (P less than 0.05), mass (P less than 0.001), serum testosterone (P less than 0.05), force production (P less than 0.05-0.01) and blood lactate (P less than 0.05) in the 60-s maximal anaerobic test. There were no significant correlations between muscle fibre characteristics and maximal oxygen uptake. The present study assumes that heredity partly affects the selection of sporting event. Growth, development and training are associated with muscle fibre area, which affects the physical performance capacity of the neuromuscular system in trained young boys. PMID- 1895354 TI - Recording soccer players' heart rates during matches. AB - The aim of this study was to examine the possibility of obtaining information about the heart rate and physiological load imposed on soccer players during a game. The study was conducted on 27 soccer players, 9 each from semi professional, university and recreational soccer teams. Players from all positions (attack, midfield and defence) were selected for the study. Each subject's heart rate was monitored during a match using a short-range radio telemetry (Sport Tester PE3000), and was sampled at 5-s intervals. The results indicate that it is possible to monitor successfully the heart rate of players with such equipment. The mean heart rate and standard deviation for each player during match play were: semi-professional players (172 +/- 12, 176 +/- 9 and 166 +/- 15 for forwards, midfielders and defenders, respectively); university players (171 +/- 13, 173 +/- 10 and 156 +/- 13 for forwards, midfielders and defenders, respectively); and recreational players (173 +/- 13, 170 +/- 12 and 162 +/- 13 for forwards, midfielders and defenders, respectively). Analysis by playing position revealed that midfield and forward players has a greater mean heart rate during a game than defensive players. To examine the suitability and accuracy of the two methods of obtaining objective data on heart rate, comparisons were made between the Sport Tester PE3000 and a standard electrocardiograph (ECG) telemetry technique. The results show that both techniques produce similar results; the former was the more convenient.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1895355 TI - The influence of cadence and power output on the biomechanics of force application during steady-rate cycling in competitive and recreational cyclists. AB - The intent of this study was two-fold. The first aim was to investigate how cyclists orient forces applied by the feet to the pedals in response to varying power output and cadence demands, and the second was to assess whether competitive riders responded differently from recreational riders to such variations. One group consisted of US Cycling Federation category II licensed competitive cyclists (n = 7) and the second group consisted of recreational cyclists with no competitive experience (n = 38). The subjects rode an instrumented stationary 10-speed geared bicycle mounted on a platform designed to provide rolling and inertial resistance for six pedal rate/power output conditions for a minimum of 2 min for each ride. The pedalling rates were 60, 80 and 100 rev min-1 and the power outputs 100 and 235 W. All rides were presented in random order. The forces applied to the pedals, the pedal angle with respect to the crank and the crank angle were recorded for the final 30 s of each ride. From these data, a number of variables were computed including peak normal and tangential forces, crank torque, angular impulse, proportion of resultant force perpendicular to the crank, and pedal angle. Both the competitive and recreational groups responded similarly to increases in cadence and power output. There was a decrease in the peak normal forces, whereas the tangential component remained almost constant as cadence was increased. Regardless of cadence, the riders responded to increased power output demands by increasing the amount of positive angular impulse. All the riders had a reduced index of effectiveness as cadence increased. This was found to be the result of the large effect of the forces during recovery on this calculation. There were no significant differences between the two groups in each of these variables over all conditions. It was concluded that the lack of difference between the groups was a combined consequence of the limited degrees of freedom associated with the bicycle and that the relatively low power output for the competitive riders was insufficient to discriminate or highlight superior riding technique. PMID- 1895356 TI - Modelling mood states in athletic performance. AB - Because moods are transitory emotional states that can be influenced by a range of personality and environmental factors, the notion that elite athletes will always tend to produce a so-called iceberg profile of mood, and that less successful performers will not, is open to question. Evidence for such a claim is based principally upon descriptive studies. The present experiment used the POMS inventory as a predictor of cross-country running performance among a group of experienced male athletes. Race times from two competitive events were plotted against each of six mood factors. Using data from race 1, a multiple-regression model--incorporating the interdependence of tension, anger and depression--was able to predict rank order of finishing positions for race 2 with acceptable accuracy (rs = 0.74, P less than 0.01). The present approach differs from the traditional model of mood research in sport in that it provides a prescriptive, rather than a descriptive, focus. Although the model that has been developed appears promising, it is likely that in sports where demands on athletes are very different from those made upon cross-country runners, an alternative model may be required. PMID- 1895357 TI - Muscle soreness and serum enzyme activity following consecutive drop jumps. AB - The purpose of this study was to evaluate changes in muscle soreness and serum enzyme activity following consecutive drop jumps. Seven male subjects (mean age 30.6 years) performed drop jumps from a 80-cm box height every 7 s until exhaustion (mean = 114 drop jumps). A questionnaire was used to assess muscle soreness (0 = no pain, 7 = unbearable painful) both pre- and post-exercise (0, 12, 24, 36 and 48 h, and 3, 4 and 5 days after the exercise). Blood samples were also taken from three subjects at each of these times. For the other four subjects, blood samples were taken pre-exercise and 0, 12 and 36 h and 5 days post-exercise only. Although there was large inter-subject variability in the development of muscle soreness, all the subjects reported muscle soreness in their lower extremity muscles, especially in the quadriceps femoris. Muscle soreness developed significantly (P less than 0.01) over time, its peak (mean +/- S.E. = 3.7 +/- 0.7) occurring 12-48 h post-exercise. Serum enzyme activity changed significantly over time (P less than 0.05), but the changes were small. Not one subject showed a large increase in creatine kinase, and the average increase was less than 1.3 times as much as the pre-exercise level throughout the period of study. These results suggest that the muscle damage that occurs after drop jumping is not associated with a large release of muscle enzymes into the blood, and muscle soreness is not necessarily related to enzyme elevation following drop jumps. PMID- 1895358 TI - Limits of energy turnover in relation to physical performance, achievement of energy balance on a daily basis. AB - Limits of energy turnover in relation to physical performance were addressed in terms of upper and lower limit, changes during a training programme and how to regulate energy balance at a changing energy turnover. At the lower limit we stress the risk of energy restriction to reach a desired body size or body composition for reduced performance, early osteoporosis and weight cycling. The upper limit of energy turnover can be increased by the consumption of energy dense carbohydrate-rich foods. Training induces an increase in energy turnover which can initially be more then twice the calculated energy costs from laboratory measurements of physical activity. In the long term, training can induce a reduction in resting energy expenditure even while the active cell mass (muscle mass) of the body has increased. The regulation of energy balance on a day to day basis seems to be better at high levels of energy turnover either as a consequence of the physiological need or as a consequence of the fact that athletes performing at a high level of energy expenditure have learned to ingest as much food as possible. PMID- 1895359 TI - Fluid and electrolyte loss and replacement in exercise. AB - Prolonged exercise leads to a progressive water and electrolyte loss from the body as sweat is secreted to promote heat loss. The rate of sweating depends on many factors and is increased in proportion to the work rate and the environmental temperature and humidity. Sweat rate is highly variable between individuals, and can exceed 21 h-1 for prolonged periods. Since it is established that dehydration will impair exercise capacity and can pose a risk to health, the intake of fluid during exercise to offset sweat loss is important. Fluid intake is also aimed at providing a source of substrate, usually in the form of carbohydrate. The availability of ingested fluids may be limited by gastric emptying or by intestinal absorption. Gastric emptying of liquids is slowed by the addition of carbohydrate in proportion to the carbohydrate concentration and osmolality of the solution. With increasing glucose concentration, the rate of fluid delivery to the small intestine is decreased, but the rate of glucose delivery is increased. Water absorption in the small intestine is a passive process and is stimulated by the active absorption of glucose and sodium. The optimum fluid for rehydration during exercise depends on many factors, particularly the intensity and duration of the exercise, the environmental conditions, and the individual physiology of the athlete. There is no advantage to fluid intake during exercise of less than 30 min duration. The composition of fluids to be used will depend on the relative needs to replace water and to provide substrate. Where rehydration is a priority the solution should contain some glucose and sodium and should not exceed isotonicity: this will require the glucose concentration to be low (20-309 g l-1) or the substitution of glucose polymers, and the sodium content to be high (perhaps as much as 60 mmol l-1). Where substrate provision is more important, a more concentrated solution, incorporating large amounts of glucose polymers in concentrations of 150-200 g l 1, is to be preferred. To minimize the limitation imposed by the rate of gastric emptying, the volume of fluid in the stomach should be kept as high as is comfortable by frequent ingestion of small amounts of fluid. Addition of sodium, and perhaps also of potassium, may be important for rehydration after exercise. PMID- 1895360 TI - Heat--sweat--dehydration--rehydration: a praxis oriented approach. AB - In any situation where heat production as a result of physical exercise exceeds heat elimination from the body by radiation and convection, the body will depend on sweat secretion and evaporation for its thermoregulation. Sweat secretion will reach maximal levels at high energy expenditures in the heat but will be limited when exercising in the cold climate. Athletes and their coaches should understand some of the principles of thermoregulation in order to make an adequate decision about optimal fluid and carbohydrate replacement in a specific situation. In general it is advised that the carbohydrate content of rehydration drinks should be low (max 80 g l-1) when sweat loss is maximal, may be intermediate when both carbohydrate availability and moderate dehydration influence performance (up to 110 g l-1), and may be maximal (up to 160 g l-1) when the sweat loss is minimized and carbohydrate is the major determinant of the rate of fatigue development. Sodium should be added to rehydration drinks in order to maximize fluid and carbohydrate absorption. A range of electrolyte values for replacement of sweat induced losses, based on whole body wash down procedure is presented. PMID- 1895361 TI - Carbohydrates and exercise. AB - Muscle glycogen and blood glucose are important substrates for contracting skeletal muscle during exercise and fatigue often coincides with depletion of these carbohydrate reserves. Carbohydrate utilization during exercise is influenced by several factors including exercise intensity and duration, training status, diet, environment and gender. In view of the importance of carbohydrates for exercise performance, active individuals should ensure their diet contains sufficient carbohydrate. For athletes engaged in heavy training the daily carbohydrate requirement may be as high as 9-10 g carbohydrate per kg body mass in order to guarantee adequate carbohydrate availability prior to and during exercise and to allow full recovery of carbohydrate reserves following exercise. PMID- 1895362 TI - Timing and method of increased carbohydrate intake to cope with heavy training, competition and recovery. AB - Based upon the fact that fatigue during intense prolonged exercise is commonly due to depletion of muscle and liver glycogen which limits both training and competitive performance, this paper has proposed extraordinary dietary practices which generally advocate high carbohydrate intake at all times before, during and after exercise. The simple goal is to have as much carbohydrate in the body as possible during the latter stages of prolonged intense exercise when the ability for intense exercise usually becomes limiting to performance. This theory is put into practice by recommending that carbohydrate intake after exhaustive exercise should average 50 g per 2 h of mostly moderate and high glycaemic carbohydrate foods. The aim should be to ingest a total of about 600 g in 24 h. Carbohydrate intake should not be avoided during the 4 h period before exercise and in fact it is best to eat at least 200 g during this time. When possible, carbohydrate should be ingested during exercise, generally in the form of solutions containing glucose/sucrose/maltodextrins, at a rate of 30-60 g h-1. Emphasis has been placed upon eating the optimal amount and best type of carbohydrate at the proper times because these practices demand a large amount of food. When diet is not carefully planned according to these guidelines, endurance athletes tend to consume too little carbohydrate because they become satiated with high fat in their diet and they go through periods in the day when recovery of glycogen stores is suboptimal and thus precious time is wasted. PMID- 1895363 TI - Effect of exercise on protein requirements. AB - The effect(s) of exercise on dietary protein requirements has (have) been a controversial topic for many years. Although most expert committees on nutrition have not provided an additional allowance of protein for active individuals, a considerable amount of experimental evidence has accumulated during the past 15 years which indicates that regular exercise does in fact increase protein needs. Part of the confusion is due to methodological difficulties and inadequate control of several interacting factors including: diet composition, total energy intake, exercise intensity, duration and training, ambient temperature, gender, and perhaps even age. Although definitive dietary recommendations for various athletic groups must await future study, the weight of current evidence suggests that strength or speed athletes should consume about 1.2-1.7 g protein/kg body weight.d-1 (approximately 100-212% of current recommendations) and endurance athletes about 1.2-1.4 g/kg.d-1 (approximately 100-175% of current recommendations). These quantities of protein can be obtained from a diet which consists of 12-15% energy from protein, unless total energy intake is insufficient. There is no evidence that protein intakes in this range will cause any adverse effects. Future studies with large sample sizes, adequate controls, and performance as well as physiological/biochemical measures are necessary to fine tune these recommendations. PMID- 1895364 TI - Importance of fat as a support nutrient for energy: metabolism of athletes. AB - The two main fuels for muscle metabolism are carbohydrate and fat. There is a limited store of carbohydrate in the body but this is not the case with fat. The average lean man has about 15% of his body weight as fat, whereas the average lean women has about 25% of her body weight as fat. Male and female endurance athletes have only about 7-10% of their body weights as fat. Sedentary people consume diets which contain about 35-40% of their energy intake as fat. The recommended intake of fat in the diet of active and sedentary people is less than that percentage. Although there is a need to increase carbohydrate intake as part of the preparation for heavy training and competition there is no need to supplement the normal diet with additional fat. Fat is mobilized from adipose tissue in response to stimulation of an intracellular lipase by the catecholamines. The products of the hydrolysis of triglycerides, the storage form of fat, are fatty acids and glycerol. The 'free' fatty acids are transported to muscle in loose combination with plasma albumin where they are released and taken up and oxidized. Glycerol is not used directly as a substrate but undergoes gluconeogenesis in the liver. This process helps restock liver glycogen stores which, in turn, provides glucose as a fuel for the central nervous system and for muscle metabolism. Training increases the capacity of skeletal muscles to use fat as an energy source. An increase in fat metabolism during prolonged exercise has a glycogen sparing effect and as such improves endurance capacity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1895365 TI - Vitamin supplementation and physical exercise performance. AB - Vitamins, just as minerals and trace elements, meet with great interest in the world of sports because of their supposed role in enhancing physical performance. Of the 13 compounds now considered as vitamins, most water-soluble vitamins and vitamin E are involved in mitochondrial energy metabolism. The influence of vitamin supplementation on mitochondrial metabolism is largely unknown. The principal argument for vitamin supplementation is the assumed increased vitamin requirement of athletes. Theoretically, an increased requirement can be caused by decreased absorption by the gastrointestinal tract, increased excretion in sweat, urine and faeces, increased turnover, as well as biochemical adaptation to training. Of course, a marginal low vitamin status can simply be the consequence of a long-term inadequate intake. However, considering the RDAs there are no indications that long-term vitamin intake among athletes is insufficient. Neither are there indications that vitamin excretion or turnover is increased in athletes. However, it is very likely that the (apparently) increased requirement is the consequence of biochemical adaptation to training and does not indicate a decreased intake. Although a marginal vitamin status, induced by inadequate vitamin intake, may have a negative effect on performance, there is no evidence to support the view that this occurs in trained athletes. Moreover, vitamin supplementation in athletes with an adequate vitamin status has no effect on physical working capacity. Possibly, exceptions have to be made for the use of vitamin E at high altitudes and for the use of vitamin C and multiple B-vitamin supplements in hot climates. PMID- 1895366 TI - Minerals: exercise performance and supplementation in athletes. AB - This paper examines whether mineral supplements are necessary for athletes, and whether these supplements will enhance performance. Macrominerals (calcium, magnesium, and phosphorus) and trace minerals (zinc, copper, selenium, chromium, and iron) are described. Calcium supplements are important for the health of bones. Athletes tend to have enhanced calcium status as assessed by bone mineral density, with the notable exception of female amenorrhoeic athletes. Magnesium status is adequate for most athletes, and there is no evidence that magnesium supplements can enhance performance. Phosphorus status is adequate for athletes. Phosphorus supplementation over an extended period of time can result in lowered blood calcium, however, some studies have shown that acute 'phosphate loading' will enhance performance. Athletes may have a zinc deficiency induced by poor diet and loss of zinc in sweat and urine. Limited data exist on the relationship of performance and zinc status. Widespread deficiencies in copper have not been documented, and there are no data to suggest that copper supplementation will enhance performance. There is no reason to suspect a selenium deficiency in athletes. The relationship between selenium status and performance has not been established, but selenium may play a role as an antioxidant. Because of the low intakes of chromium for the general population, there is a possibility that athletes may be deficient. Exercise may create a loss in chromium because of increased excretion into the urine. Many athletes, particularly female, are iron depleted, but true iron deficiencies are rare. Iron depletion does not affect exercise performance but iron deficiency anaemia does. Iron supplements have not been shown to enhance performance except where iron deficiency anaemia exists. In conclusion, poor diets are perhaps the main reason for any mineral deficiencies found in athletes, although in certain cases exercise could contribute to the deficiency. Mineral supplementation may be important to ensure good health, but few studies have definitively documented any beneficial effect of mineral supplementation on performance. PMID- 1895367 TI - Evaluation of adnexal masses with transvaginal color ultrasound. AB - We evaluated 14,317 asymptomatic or minimally symptomatic women for ovarian carcinoma with transvaginal color Doppler ultrasound. The resistance index was calculated for at least five separate cardiac cycles in each case, and the mean was calculated. We discovered 624 benign adnexal masses: in every case except one the resistance index was greater than 0.40. There were 56 malignant adnexal masses, 16 of which were stage I ovarian cancers. Neovascularization was found in six of the seven stage I primary neoplasms and in all of the nine stage I secondary ovarian cancers. In all, the RI was less than or equal to 0.40. There were 40 advanced ovarian cancers revealed (stage III or IV); 39 showed abnormal color-flow pattern with the resistance index less than 0.04. PMID- 1895368 TI - Fetal sucking of the umbilical cord. PMID- 1895369 TI - Effect of calcium channel blocker nifedipine on uterine artery flow velocity waveforms. AB - Calcium channel blockers have been used successfully in the treatment of pregnancy hypertension and premature labor. Only limited information related to their effect on uterine blood flow during pregnancy is available. In this study we measured the ratio between peak systolic to end-diastolic flow velocity (S/D ratio) in the ascending branch of the uterine artery in nine pregnant patients prior to and following a 10-mg dose of sublingual nifedipine. Another group of seven matched patients who received a placebo served as a control group. All studies were performed between 17 and 22 weeks gestation. The S/D ratio decreased shortly after sublingual nifedipine, but the change was not significant. It increased gradually afterward so that by 60 minutes it returned to the control value. The mean systolic blood pressure decreased by 8.6% to its lowest value after 25 minutes (P less than 0.01). The mean diastolic blood pressure decreased by 15.7% to its lowest value after 35 minutes (P less than 0.002). Maternal heart rate did not change significantly. No significant changes were observed in any of the measured variables in the placebo group. In conclusion, nifedipine does not induce significant changes in uterine arterial resistance in midtrimester and may be considered during pregnancy, providing that large fluctuations in maternal blood pressure are avoided. PMID- 1895370 TI - In vitro validation of Doppler indices using blood and water. AB - Using an in vitro flow model, volume flow and pressure were measured to compare calculated resistance with simultaneously measured continuous-wave Doppler indices during imposed changes in downstream resistance to pulsatile flow. With stepwise reductions in flow, the peak (S) and trough (D) points of the maximum shifted-frequency envelope fell in parallel in a linear fashion until D reached zero. Pressure remained constant, and the pressure waveform remained unchanged. As calculated resistance increased, resistance index (RI) and pulsatility index (PI) both increased in a linear fashion until the point at which D became zero. However, S/D ratio was not linear, and the slope increased as resistance increased. The results obtained from microspheres suspended in water and with heparinized sheep's blood were similar. The results indicate that, with reductions in flow at constant pressure in vitro, S/D ratio does not relate to calculated resistance in the same linear manner as PI and RI. PMID- 1895371 TI - Role of umbilical Doppler velocimetry in the biophysical assessment of the growth retarded fetus. Answers from neonatal morbidity and mortality. AB - We compared umbilical Doppler velocimetry with biophysical parameters, obstetrical management, and neonatal morbidity. The study of 85 pregnancies was prospective and blind both to the obstetric and pediatric staff. Our results show that under the same biophysical diagnosis, ie, abnormal fetal growth, oligohydramnios, and nonreactive cardiotocographics, the prevalence of neonatal morbidity was significantly higher in fetuses with associated abnormal umbilical pulsatility index (PI) in utero. Newborns with abnormal PI were delivered earlier, mostly for fetal indication, and were smaller and more asymmetrical than newborns with a normal PI in utero. The analysis of morbidity for homogeneous classes of weight showed that in the group of newborns between 1500 and 2500 g, newborns with normal umbilical PI did show only metabolic disturbances and one respiratory distress syndrome. On the contrary, newborns of the same gestational age and of the same weight with abnormal PI had more severe morbid episodes. In the class of weight between 1500 and 1000 g not only the severity but also the prevalence of neonatal morbidity was significantly higher in newborns with an abnormal PI in utero. None of the newborns delivered below 1000 g had a normal umbilical PI. Five died in the early neonatal period. Three suffered from mild neuromotor sequelae. Practical consequences of these findings on fetal management are the scheduled frequency of biophysical examinations, which must be closer and on an inpatient basis whenever abnormal, and the interpretation of other abnormal biophysical parameters, which must be considered as more severe whenever associated with an abnormal umbilical velocimetry. PMID- 1895372 TI - Noninvasive vascular studies. PMID- 1895373 TI - Comparison of the pulsatility index and input impedance parameters in a model of altered hemodynamics. AB - Clinical use of Doppler waveform analysis assumes that vascular resistance is accurately represented by the Doppler indices. This assumption was examined by correlating the pulsatility index (PI) with measures of input impedance including peripheral vascular resistance (Zpr), characteristic impedance (Zo), and reflection coefficient (Rc). Assessment of these parameters from the descending aorta was performed in five chronically instrumented, newborn lambs subjected to administration of norepinephrine and hydralazine. Significant increases in PI, Zpr, Zo, and Rc were seen in response to administration of norepinephrine, and decreases in PI and Zpr occurred with hydralazine use. Significant correlation existed between PI and Zpr throughout the study, but changes in PI did not correlate with changes in Zo and Rc. PI appears to reflect changes in Zpr accurately. However, the lack of ability for PI to assess Zo or Rc requires further investigation. PMID- 1895374 TI - Can umbilical artery pulsatility index predict the outcome of fetuses with structural heart disease? AB - Umbilical artery Doppler waveforms have been suggested to demonstrate diminished end-diastolic velocities in anomalous fetuses. We evaluated 11 fetuses with antenatally diagnosed congenital heart disease (CHD) and compared them to a normal population. Fetuses with CHD were studied once each and ranged in age from 19 to 32 weeks gestation. Eight had normal chromosomes, and three were aneuploid. The pulsatility index (PI) was elevated (above the 90th percentile for gestational age) in 3/11 CHD fetuses (P = NS). Elevated PI did not discriminate well between those with fatal and nonfatal lesions. Although all three fetuses with elevated PI had fatal disease, five of eight fetuses with fatal anomalies had normal PI values. We conclude that, while umbilical artery PI values were elevated in a subgroup of affected fetuses, this was not clinically helpful. PMID- 1895375 TI - Doppler evaluation of the fetoplacental circulation in the latent phase of preterm premature rupture of membranes. AB - Blood velocity waveform analysis by pulsed Doppler ultrasonography in preterm premature rupture of membranes is described. Reduced amounts of amniotic fluid did not impair determination of the resistance indices from the umbilical artery. Good results were obtained from the internal carotid artery in 82% of cases. Failure in measurements at the internal carotid artery occurred when fetal head engagement prevented good study planes. Ninety-three percent of umbilical artery determinations fell within the normal limits for our control population as did 89.2% of those at the internal carotid artery. No differences in the resistance indices could be attributed to the length of the latent period in prematurely ruptured membranes or subclinical chorioamnionitis. Therefore, if a mother or fetus has an underlying condition that affects fetoplacental circulation, the resulting abnormal blood velocity waveform should reflect this condition rather than the effect of ruptured membranes. PMID- 1895376 TI - Doppler velocimetry versus nonstress test in the antepartum monitoring of low risk pregnancies. AB - One thousand singleton low-risk pregnancies were cross-sectionally studied at 36 40 weeks gestation with continuous-wave Doppler ultrasonography in order to assess its usefulness as an antepartum monitoring technique for the identification of fetuses at risk of developing an adverse outcome. Uterine artery and umbilical artery S/D values were measured and related to fetal outcome. Results were compared with those of the nonstress test. No significant differences in fetal outcome, with the exception of birth weight, were found between patients with normal and abnormal uterine S/D values. In pregnancies with abnormal umbilical S/D values, a higher incidence of cesarean section for fetal distress and lower birth weight were observed. Moreover, those newborns more frequently had complications such as low 5-minute Apgar score, requiring resuscitation and admission to the intensive care unit. When compared to nonstress test, umbilical velocimetry showed a higher efficiency in identifying fetuses at risk for adverse outcome. PMID- 1895377 TI - Value of a random single Doppler study of the umbilical artery for predicting perinatal outcome. AB - A prospective blinded study was performed on 191 high-risk patients with pregnancies ranging from 25 to 42 weeks gestation to investigate the value of a single Doppler analysis of the umbilical artery blood flow waveform (systolic-to diastolic ratio, S/D) for predicting poor perinatal outcome. This was defined as the presence of heavy meconium, delivery of a growth-retarded infant, an umbilical cord arterial pH less than 7.2, or a 5-minute Apgar score less than 7. The interval between Doppler examination and delivery ranged from 12 hours to 15 weeks. No clinical data were available to the examiner performing the Doppler study. Moreover, the Doppler measurements were unknown to the attending physicians. The sensitivity, specificity, and positive and negative predictive values of the Doppler study in predicting outcome were 30.4%, 92.9%, 36.8%, and 92.6%, respectively, with an adverse outcome prevalence of 12%. These results indicate that a single random S/D ratio from the umbilical artery is not an adequate screening test for the risk of perinatal complications. PMID- 1895378 TI - Color-flow and Doppler velocimetry in prenatal diagnosis of acardiac triplet. PMID- 1895379 TI - Identification of a signal necessary for initiation of reverse transcription of the hepadnavirus genome. AB - Reverse transcription of the hepadnavirus genome initiates near the 3' end of the RNA template and has previously been shown to depend on sequences flanking the initiation site for DNA synthesis (C. Seeger and J. Maragos, J. Virol. 64:16-23, 1990). DNA synthesis leads to the covalent attachment of a protein to the 5' end of minus-strand DNA, and it is generally believed that this protein serves as the primer for reverse transcription. To examine priming in more detail, we have carried out a detailed genetic analysis of the nucleotide sequences at the origin of minus-strand DNA synthesis characterized in our earlier study. This mutational analysis has led to the identification of a short, four-nucleotide-long sequence as the signal for initiation of reverse transcription. This signal is a UUUC sequence motif flanking the position of the 5' end of minus-strand DNA, which alone is not sufficient for DNA synthesis, indicating that positional effects are also important to specify the origin of DNA synthesis. PMID- 1895380 TI - Critical chemical features in trans-acting-responsive RNA are required for interaction with human immunodeficiency virus type 1 Tat protein. AB - The human immunodeficiency virus type 1 Tat protein binds to an RNA stem-loop structure called TAR which is present at the 5' end of all human immunodeficiency virus type 1 transcripts. This binding is centered on a bulge within the stem of TAR and is an essential step in the trans-activation process which results in a dramatic increase in viral gene expression. By analysis of a series of TAR derivatives produced by transcription or direct chemical synthesis, we determined the structural and chemical requirements for Tat binding. Tat binds well to structures which have a bulge of two to at least five unpaired bases bounded on both sides by a double-stranded RNA stem. This apparent flexibility in bulge size is in contrast to an absolute requirement for an unpaired uridine (U) in the 5' most position of the bulge (+23). Substitution of the U with either natural bases or chemical analogs demonstrated that the imido group at the N-3 position and, possibly, the carbonyl group at the C-4 position of U are critical for Tat binding. Cytosine (C), which differs from U at only these positions, is not an acceptable substitute. Furthermore, methylation at N-3 abolishes binding. While methylation of U at the C-5 position has little effect on binding, fluorination reduces it, possibly because of its effects on relative tautomer stability at the N-3 and C-4 positions. Thus, we have identified key moieties in the U residue that are of importance for the binding of Tat to TAR RNA. We hypothesize that the invariant U is involved in hydrogen bond interactions with either another part of TAR or the TAR-binding domain in Tat. PMID- 1895381 TI - Predominant binding of Theiler's viruses to a 34-kilodalton receptor protein on susceptible cell lines. AB - Western immunoblots of BHK-21 cell lysates probed with the highly virulent GDVII and the less virulent BeAn strains of Theiler's murine encephalomyelitis virus (TMEV) revealed predominant binding to a 34-kDa membrane protein and much lower levels of binding to 100- and 18-kDa membrane proteins. Complete inhibition of virus binding to both the 34- and 18-kDa membrane species by excess unlabeled TMEV demonstrated specificity of binding. Virus binding was also blocked by wheat germ agglutinin, which specifically binds to sialic acid residues and blocks TMEV binding to whole BHK-21 cells. Radiolabeled TMEV also bound to 100-, 34-, and 18 kDa membrane proteins expressed on other TMEV permissive cell lines but not on the nonpermissive cell lines tested. These data suggest that a 34-kDa cellular protein may be the primary determinant of susceptibility to TMEV infection by mediating the binding of GDVII and BeAn viruses to susceptible cells. PMID- 1895382 TI - Regulation of the biosynthesis of subgroup C adenovirus protein IVa2. AB - The IVa2 gene is located between 16 and 11.3 map units on the left strand of the adenovirus type 5 (Ad5) genome. The coded RNA contains an intron of 277 nucleotides. To determine whether protein IVa2 is synthetized during productive infection and to obtain an immunological reagent to study its function, we prepared antibodies directed to 414 amino acids of protein IVa2 fused to the N terminal domain of Staphylococcus aureus protein A. Western immunoblot analysis of viral proteins demonstrates that protein IVa2 is a minor component of mature viral particles and that it is also present in assembly intermediates and young virions. Thus, contrary to a previous report (H. Persson, B. Mathisen, L. Philipson, and U. Pettersson, Virology 93:198-208, 1979), protein IVa2 is not related to the 50-kDa polypeptide, a scaffolding protein present in assembly intermediates. The biosynthesis of protein IVa2 during productive infection was examined. Time course studies using immunofluorescence analysis with polyclonal antibodies targeted to protein IVa2 revealed that this protein is first synthesized at 12 h in a few cells exhibiting very striking fluorescence. Synthesis continues until at least 24 h postinfection. When hydroxyurea is added, protein IVa2 is not detected. In cells infected with mutant H5 ts125, blocked at the nonpermissive temperature (40 degrees C) in viral DNA replication, protein IVa2 is overexpressed. These results suggest that protein IVa2 synthesis requires cellular rather than viral DNA replication. RNase protection assay results indicate that hydroxyurea inhibits protein IVa2 synthesis at the transcriptional level. Thus, overexpression of protein IVa2 in H5 ts125-infected cells may be regulated at the translational level. PMID- 1895383 TI - The hydrophobic membrane-spanning sequences of the gp52 glycoprotein are required for the pathogenicity of Friend spleen focus-forming virus. AB - Friend spleen focus-forming virus (SFFV) codes for a transport-defective envelope glycoprotein designated gp52, which is responsible for the leukemogenic properties of the virus. gp52 is a monotopic integral membrane protein anchored in the membrane by a stretch of hydrophobic amino acid residues located near the carboxy terminus of the molecule. We have constructed a mutant SFFV envelope gene in which the sequences that code for the hydrophobic membrane-spanning domain have been deleted, and we expressed this gene by using recombinant vaccinia virus vectors or retroviral vectors. The mutant SFFV envelope gene was found to encode a truncated glycoprotein (gp52t) which was also transport defective; a majority of gp52t remained cell associated, while a small proportion of the molecules underwent oligosaccharide processing. The processed form of gp52t was secreted from the cells. Retroviral vectors carrying the mutant SFFV envelope gene were found to be nonpathogenic in adult mice. These results indicate that the hydrophobic membrane-spanning region of gp52 is required for pathogenicity of SFFV and suggest that these sequences may play a role in signal transduction. The results also indicate that the transport defect of SFFV gp52 is due to structural features of the ectodomain of the molecule. PMID- 1895384 TI - Novel regulatory properties of the IE1 and IE0 transactivators encoded by the baculovirus Autographa californica multicapsid nuclear polyhedrosis virus. AB - The baculovirus Autographa californica multicapsid nuclear polyhedrosis virus expresses two immediate-early genes from the HindIII-G region (map units 90.4 to 96.8) of the genome. During the early phase of infection, nonspliced 1.9-kb and spliced 2.1-kb transcripts are expressed which encode the IE1 and IE0 (spliced IE1) gene products, respectively. These two gene products differ only in that IE0 contains an additional 54 amino acids at the amino terminus. RNA analysis of these two genes during infection revealed that they were differentially expressed. IE1 was expressed early and late, whereas IE0 was expressed only early in infection. The regulation of these two immediate-early genes was analyzed by transient expression assays. The IE1 gene product stimulated expression of IE1 promoter-directed expression but down-regulated expression from the IE0 promoter. The IE0 gene product also transactivated the IE1 promoter but did not affect expression from its own promoter. Unlike IE1, which transactivates the delayed early 39K gene in the presence and absence of the homologous region (hr) enhancers, IE0 transactivated the 39K promoter only in the presence of cis-linked hr5 enhancer. The results of this study in conjunction with previous results suggest that the IE1 gene encodes a multifunctional gene product that may be involved in (i) repression of immediate-early gene expression, (ii) continued expression of its own gene product during infection, and (iii) transactivation of the delayed early and late classes of genes. PMID- 1895385 TI - Identification and characterization of intragenic sequences which repress human immunodeficiency virus structural gene expression. AB - Examination of the life cycle of the human immunodeficiency virus (HIV) has shown that multiple levels of regulation exist, including some which require the virus encoded Rev protein. In the absence of Rev, mRNAs encoding the structural proteins remain untranslated, a phenomenon which appears, in part, to be caused by nuclear entrapment of these RNA species. To examine the basis for repression of structural gene mRNA expression, a heterologous assay system was utilized to determine whether regions present within gag and pol contain elements capable of suppressing gene expression when present in cis. Both genes were found to contain cis-acting repressor sequences (CRS) that block gene expression when present within the 3' untranslated portion of a heterologous gene transcript. The element within pol was found to have the strongest repressive effect. While Rev alone was unable to reverse the repression observed with the pol sequence, addition of the env Rev-responsive element (RRE) in cis and Rev in trans did cause reversal of inhibition. Deletion mutagenesis defined a 260-bp element within the 3' portion of pol that contains a potent CRS which functions when present in the sense orientation. The corresponding region in HIV-2 pol was found to contain a functionally similar CRS element. To examine the mechanism of repression, the effects of the CRS elements on both the abundance and subcellular distribution of the mRNAs were examined. Neither was dramatically altered when examined in the context of a heterologous reporter (chloramphenicol acetyltransferase) mRNA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1895387 TI - Generation of recombinant murine retroviral genomes containing the v-src oncogene: isolation of a virus inducing hemangiosarcomas in the brain. AB - A series of recombinant retroviral genomes was generated by cotransformation of NIH 3T3 cells with a mixture of cloned DNAs: a proviral copy of the wild-type Moloney murine leukemia virus, and Moloney-based vectors containing defective copies of the chicken v-src and the murine v-abl oncogenes. Morphologically transformed foci, appearing at low frequencies in these cultures, released high titers of transforming viruses. Analysis of one group of these viruses showed that the genomes were recombinants containing portions of the viral gag gene juxtaposed to the v-src oncogene. Biologically active cloned DNAs of two of these viruses were obtained and mapped in detail. One of these viruses did not cause disease after inoculation into newborn mice, but the other induced rapidly fatal hemangiosarcomas located exclusively in the brain. PMID- 1895386 TI - Mutational analysis of N-linked glycosylation sites of Friend murine leukemia virus envelope protein. AB - The roles played by the N-linked glycans of the Friend murine leukemia virus envelope proteins were investigated by site-specific mutagenesis. The surface protein gp70 has eight potential attachment sites for N-linked glycan; each signal asparagine was converted to aspartate, and mutant viruses were tested for the ability to grow in NIH 3T3 fibroblasts. Seven of the mutations did not affect virus infectivity, whereas mutation of the fourth glycosylation signal from the amino terminus (gs4) resulted in a noninfectious phenotype. Characterization of mutant gene products by radioimmunoprecipitation confirmed that glycosylation occurs at all eight consensus signals in gp70 and that gs2 carries an endoglycosidase H-sensitive glycan. Elimination of gs2 did not cause retention of an endoglycosidase H-sensitive glycan at a different site, demonstrating that this structure does not play an essential role in envelope protein function. The gs3- mutation affected a second posttranslational modification of unknown type, which was manifested as production of gp70 that remained smaller than wild-type gp70 after removal of all N-linked glycans by peptide N-glycosidase F. The gs4- mutation decreased processing of gPr80 to gPr90, completely inhibited proteolytic processing of gPr90 to gp70 and Pr15(E), and prevented incorporation of envelope products into virus particles. Brefeldin A-induced mixing of the endoplasmic reticulum and parts of the Golgi apparatus allowed proteolytic processing of wild type gPr90 to occur in the absence of protein transport, but it did not overcome the cleavage defect of the gs4- precursor, indicating that gs4- gPr90 is resistant to the processing protease. The work reported here demonstrates that the gs4 region is important for env precursor processing and suggests that gs4 may be a critical target in the disruption of murine leukemia virus env product processing by inhibitors of N-linked glycosylation. PMID- 1895388 TI - Synthesis of leader RNA and editing of the P mRNA during transcription by purified measles virus. AB - A transcription system with detergent-disrupted purified measles virus was developed. Synthesis of authentic, full-length measles virus N, P, M, and F mRNAs by purified virus occurred as identified by dot-blot hybridization analysis of individual measles virus clones and gel electrophoresis. The relative abundance of the first five viral mRNAs synthesized in vitro decreased significantly with their distance from the 3' end. The addition of the soluble protein fraction from uninfected A549 cells stimulated overall viral RNA synthesis but did not alter the relative abundance of each of the mRNAs. Measles virus synthesized in vitro a leader RNA of approximately 55 nucleotides in length, suggesting that like other negative-strand viruses, transcription initiated only at the 3' end of the genome RNA. Purified measles virus also catalyzed RNA editing during the synthesis of the P mRNA as shown by modified primer extension analysis of the mRNA products and by translation of the modified RNA into the V protein in rabbit reticulocyte lysates. These data suggested that the RNA editing activity was virus encoded. PMID- 1895389 TI - Deletion of a GC-rich region flanking the enhancer element within the long terminal repeat sequences alters the disease specificity of Moloney murine leukemia virus. AB - Moloney murine leukemia virus (M-MuLV) is a replication-competent retrovirus which induces T-lymphoblastic lymphoma 2 to 4 months after inoculation. Enhancer sequences in the U3 region of the M-MuLV long terminal repeat, primarily the 75 bp tandem repeats, strongly influence the disease specificity and latency of M MuLV. We investigated the role of GC-rich sequences downstream of the tandem repeats in the disease specificity of M-MuLV. A recombinant M-MuLV lacking 23 bases of a GC-rich sequence (-174 to -151), Delta 27A M-MuLV, was tested for pathogenesis in neonatal NIH Swiss mice. Delta 27A M-MuLV induced disease with a longer latency than did M-MuLV (7 versus 3 months) in greater than 85% of inoculated mice. More interestingly, this virus showed an expanded repertoire of hematopoietic diseases. Molecular analyses and histopathologic examinations indicated that while 39% of mice inoculated with Delta 27A M-MuLV developed T cell lymphoblastic lymphoma typical of wild-type M-MuLV, the majority developed acute myeloid leukemia, erythroleukemia, or B-cell lymphoma. Viral DNA corresponding to Delta 27A M-MuLV was detectable in most of the tumors analyzed. These findings indicate that the GC-rich region significantly influences the disease specificity and latency of M-MuLV. PMID- 1895390 TI - Complex formation between the lymphotropic papovavirus large tumor antigen and the tumor suppressor protein p53. AB - The simian B-lymphotropic papovavirus (LPV) encodes a large tumor antigen (T antigen) which is 45% identical to both the simian virus 40 (SV40) and the polyomavirus (PyV) large T antigens. In transgenic mice, the transforming properties of the LPV T antigen are similar to those of the SV40 T antigen. However, little is known about its biochemical activities. Since SV40 T antigen forms a complex with and stabilizes the host cell tumor suppressor protein p53 while the PyV large T antigen does not, we characterized the LPV T antigen for its ability to complex p53. We demonstrate an association between LPV T antigen and p53 in both a tumor-derived cell line and BALB/c 3T3 cells transformed in culture. A third protein of approximately 68 kDa which was found associated with the LPV T antigen-p53 complex in tumor-derived cells appears to be heat shock protein 70 (hsp70). The half-life of p53 in all LPV T-antigen-transformed cells was extended significantly; i.e., it was 3 to 7 h compared with 19 minutes in BALB/c 3T3 cells. The half-life of the LPV T antigen itself was 5 to 9 h depending on the cell line origin. That p53 was stabilized because of association with LPV T antigen and not because of mutation was demonstrated with the p53 conformation-dependent monoclonal antibody PAb246. This antibody distinguishes between wild-type p53 (PAb246+) and mutant, oncogenic p53 (PAb246-). Sequential immunoprecipitation showed all detectable p53 to be of the PAb246+ class in each LPV-transformed cell line, suggesting that the stable p53 was indeed wild type. PMID- 1895391 TI - Genetic diversity of the attachment protein of subgroup B respiratory syncytial viruses. AB - Respiratory syncytial (RS) virus causes repeated infections throughout life. Between the two main antigenic subgroups of RS virus, there is antigenic variation in the attachment protein G. The antigenic differences between the subgroups appear to play a role in allowing repeated infections to occur. Antigenic differences also occur within subgroups; however, neither the extent of these differences nor their contributions to repeat infections are known. We report a molecular analysis of the extent of diversity within the subgroup B RS virus attachment protein genes of viruses isolated from children over a 30-year period. Amino acid sequence differences as high as 12% were observed in the ectodomains of the G proteins among the isolates, whereas the cytoplasmic and transmembrane domains were highly conserved. The changes in the G-protein ectodomain were localized to two areas on either side of a highly conserved region surrounding four cysteine residues. Strikingly, single-amino-acid coding changes generated by substitution mutations were not the only means by which change occurred. Changes also occurred by (i) substitutions that changed the available termination codons, resulting in proteins of various lengths, and (ii) a mutation introduced by a single nucleotide deletion and subsequent nucleotide insertion, which caused a shift in the open reading frame of the protein in comparison to the other G genes analyzed. Fifty-one percent of the G-gene nucleotide changes observed among the isolates resulted in amino acid coding changes in the G protein, indicating a selective pressure for change. Maximum parsimony analysis demonstrated that distinct evolutionary lineages existed. These data show that sequence diversity exists among the G proteins within the subgroup B RS viruses, and this diversity may be important in the immunobiology of the RS viruses. PMID- 1895392 TI - Infection initiated by the RNA pregenome of a DNA virus. AB - We describe experiments demonstrating that after transfection into permissive cells, the RNA pregenome of an avian hepadnavirus, the duck hepatitis B virus, is infectious. Using a Sindbis virus expression vector, we showed that cytoplasmic synthesis of the pregenome resulted in hepadnaviral DNA synthesis. Moreover, complete infectious virus was produced from cells transfected with hepadnaviral pregenomic RNA. We conclude that the pregenome of hepadnaviruses can express all the proteins required for DNA synthesis as well as serve as a template for reverse transcription and that DNA resulting from pregenome expression can be utilized to establish a productive infection in pregenome-transfected cells. PMID- 1895393 TI - Alternative pathway for induction of human immunodeficiency virus gene expression: involvement of the general transcription machinery. AB - Human immunodeficiency virus type 1 (HIV-1) is viable and mitogen inducible in the absence of its binding sites for the inducible transcription factor NF-kappa B. We have investigated alternative mechanisms for induction of HIV-1 transcription. Using transient transfection assays, we found that transcription from an HIV-1 LTR containing mutant kappa B sites was activated 10- to 20-fold in a variety of human cell types by the phorbol ester phorbol myristate acetate (PMA). The promoter elements conferring this inducibility were localized to the region downstream of nucleotide -70, which contains the TATA and TAR elements and binding sites for transcription factors Sp1 and LBP-1. Synthetic promoters containing only Sp1 sites and a TATA element were also induced in transfection experiments as well as in in vitro transcription experiments with T-cell nuclear extracts. Moreover, promoters containing a TATA box in the absence of Sp1 sites or Sp1 sites in the absence of a TATA box were equally inducible in vitro, as was an RNA polymerase III promoter. The activities of RNA polymerases II and III and of the 38-kDa TATA-binding protein transcription factor IID (TFIID), were not induced by PMA, but electrophoretic mobility shift assays revealed a highly inducible protein-DNA complex that interacted specifically with the TATA sequence. This protein-DNA complex appeared to be much larger than that found with the 38-kDa human TFIID expressed in bacteria. Taken together, these data suggest that a component of the general transcription machinery, and possibly a TFIID-associated protein, is induced in T cells by PMA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1895394 TI - Production of hepatitis B virus nucleocapsidlike core particles in Xenopus oocytes: assembly occurs mainly in the cytoplasm and does not require the nucleus. AB - The location of hepatitis B virus (HBV) nucleocapsid (core particle) assembly in infected cells remains controversial. Some lines of evidence implicate the nucleus; others favor the cytoplasm. Via injection of a synthetic mRNA encoding the HBV nucleocapsid protein (p21.5), we have expressed both unassembled p21.5 and nucleocapsidlike core particles in Xenopus oocytes. Subcellular fractionation reveals that approximately 91% of the unassembled p21.5 and 95% of the core particles are cytoplasmic, with only 9 and 5%, respectively, in the nucleus. We present evidence showing that unassembled p21.5 equilibrates between nucleus and cytoplasm by passive diffusion and that intact core particles do not enter the nucleus. To examine the role of the nucleus in core particle formation, we expressed p21.5 in surgically anucleate oocytes. We show that anucleate oocytes support efficient core particle formation, indicating that (i) the nucleus is not essential for assembly and (ii) the cytoplasm can assemble most core particles found in oocytes. On the basis of our data, we propose that in oocytes, most core particle assembly (up to 95%) occurs in the cytoplasm, but that at least approximately 5% of the cellular core particles are assembled in the nucleus and remain there. We discuss the implications of these findings for the formation of replication-competent core particles in infected cells. PMID- 1895395 TI - Neuroattenuation of an avirulent bunyavirus variant maps to the L RNA segment. AB - The derivation and characterization of a neuroattenuated reassortant clone (RFC 25/B.5) of California serogroup bunyavirus was described previously (M. J. Endres, A. Valsamakis, F. Gonzalez-Scarano, and N. Nathanson, J. Virol. 64:1927 1933, 1990). To map the RNA segment responsible for this attenuation, a panel of reassortants was constructed between the attenuated clone B.5 (genotype TLL) and a virulent clone (B1-1a) of reciprocal genotype (LTT). Parent viruses and clones representing all of the six possible reassortants were examined for neurovirulence by intracerebral injection in adult mice. Reassortants bearing the large RNA segment from the virulent parent were almost as virulent as the virulent parent virus, while reassortants bearing the large RNA segment from the avirulent parent virus exhibited low or intermediate virulence. These results indicate that the large RNA segment is the major determinant of neuroattenuation of clone B.5. In addition to its neuroattenuation, clone B.5 was temperature sensitive and exhibited an altered plaque morphology. These phenotypes also segregated with the large RNA segment. The importance of the large RNA segment (which encodes the viral polymerase) in neurovirulence contrasts with prior studies which indicate that the ability to cause lethal encephalitis after peripheral injection of suckling mice (neuroinvasiveness) is primarily determined by the middle-sized RNA segment, which encodes the viral glycoproteins. PMID- 1895396 TI - Polymerase chain reaction analysis of defective human T-cell leukemia virus type I proviral genomes in leukemic cells of patients with adult T-cell leukemia. AB - Human T-cell leukemia virus type I (HTLV-I) is the etiologic agent of adult T cell leukemia, and the clonally derived leukemic cells all contain proviral genomes. Polymerase chain reaction with a variety of primers which span the HTLV I genome was used to determine that a significant fraction of patients (at least 32%) carry deleted viral genomes in their leukemic cells. The pX region of the HTLV-I genome encoding the regulatory genes tax and rex was preferentially retained. The fact that the tax coding region was retained provides supporting evidence that the tax protein contributes to leukemogenesis in vivo. The reasonably high fraction of patients with adult T-cell leukemia carrying deleted genomes in their tumor cells suggests that the deletions have a role in leukemogenesis. PMID- 1895397 TI - Evolutionary analysis of the influenza A virus M gene with comparison of the M1 and M2 proteins. AB - Phylogenetic analysis of 42 membrane protein (M) genes of influenza A viruses from a variety of hosts and geographic locations showed that these genes have evolved into at least four major host-related lineages: (i) A/Equine/prague/56, which has the most divergent M gene; (ii) a lineage containing only H13 gull viruses; (iii) a lineage containing both human and classical swine viruses; and (iv) an avian lineage subdivided into North American avian viruses (including recent equine viruses) and Old World avian viruses (including avianlike swine strains). The M gene evolutionary tree differs from those published for other influenza virus genes (e.g., PB1, PB2, PA, and NP) but shows the most similarity to the NP gene phylogeny. Separate analyses of the M1 and M2 genes and their products revealed very different patterns of evolution. Compared with other influenza virus genes (e.g., PB2 and NP), the M1 and M2 genes are evolving relatively slowly, especially the M1 gene. The M1 and M2 gene products, which are encoded in different but partially overlapping reading frames, revealed that the M1 protein is evolving very slowly in all lineages, whereas the M2 protein shows significant evolution in human and swine lineages but virtually none in avian lineages. The evolutionary rates of the M1 proteins were much lower than those of M2 proteins and other internal proteins of influenza viruses (e.g., PB2 and NP), while M2 proteins showed less rapid evolution compared with other surface proteins (e.g., H3HA). Our results also indicate that for influenza A viruses, the evolution of one protein of a bicistronic gene can affect the evolution of the other protein.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1895398 TI - Avian reovirus S1133 can replicate in mouse L cells: effect of pH and cell attachment status on viral infection. AB - Previous reports have suggested that avian reovirus S1133 fails to replicate in mouse L cells. In this article, we report that replication does occur under certain culture conditions. The avian reovirus was found to grow in mouse L cells at pH 6.4 and 7.2 but not at pH 8.2. Culture medium with a basic pH directly inhibited viral transcription and genome replication. As a result, viral protein synthesis was also affected. At permissive pH levels, avian reovirus grew better in monolayers than in suspension cultures of L cells because of the influence of cell attachment status on viral macromolecular synthesis. Our results not only show that avian reovirus can replicate in mouse L cells but also help to explain why it did not in previous studies. PMID- 1895399 TI - The stimulatory effect of actinomycin D on avian reovirus replication in L cells suggests that translational competition dictates the fate of the infection. AB - Indirect immunostaining of avian reovirus S1133-infected L-cell monolayers showed that most of the cells can support viral replication. However, the number of cells in which the virus was actually replicating depended on the multiplicity of virus infection. The presence of actinomycin D during infection increased viral protein synthesis, viral growth, and the number of actively infected cells at late infection times. The antibiotic elicited these effects by triggering viral replication in cells that already contained unproductive cytoplasmic virus but that would not get productively infected in the absence of the drug. From these results, we propose a model for the interaction between L cells and avian reovirus S1133 in which viral versus host mRNA competition for the translational machinery determines the fate of the virus infection. PMID- 1895401 TI - Inhibition of human immunodeficiency virus type 1 multiplication by antisense and sense RNA expression. AB - Human immunodeficiency virus type 1 (HIV-1) primarily infects CD4+ lymphocytes and macrophages and causes AIDS in humans. Retroviral vectors allowing neomycin phosphotransferase (npt) gene expression were engineered to express 5' sequences of HIV-1 RNA in the antisense or sense orientation and used to transform the human CD4+ lymphocyte-derived MT4 cell line. Cells expressing antisense or sense RNA to the HIV-1 tat mRNA leader sequence, as part of the 3' untranslated region of the npt mRNA, remained sensitive to HIV-1 infection. In contrast, resistance to HIV-1 infection was observed in cells expressing antisense RNA to the HIV-1 primer-binding site or to the region 5' to the primer-binding site as part of the 3' region of the npt mRNA. Cells expressing the tat mRNA leader sequence in the sense orientation as a precise replacement of the 5' untranslated region of npt mRNA were also resistant to HIV-1. These results indicate that sense and antisense approaches can be used to interfere with HIV-1 multiplication. PMID- 1895402 TI - Resistance to human immunodeficiency virus type 1 (HIV-1) infection in human CD4+ lymphocyte-derived cell lines conferred by using retroviral vectors expressing an HIV-1 RNA-specific ribozyme. AB - Toward gene therapy for the treatment of human immunodeficiency virus type 1 (HIV 1) infections in AIDS, Moloney murine leukemia virus-derived retroviral vectors were engineered to allow constitutive and tat-inducible expression of an HIV-1 5' leader sequence-specific ribozyme (Rz1). These vectors were used to infect the human CD4+ lymphocyte-derived MT4 cell line. The stable MT4 transformants expressing an HIV-1 RNA-specific ribozyme, under the control of the herpes simplex virus thymidine kinase (tk) promoter, were found to be somewhat resistant to HIV-1 infection as virus production was delayed. In cells allowing ribozyme expression under control of the simian virus 40 or cytomegalovirus promoter, the rate of HIV-1 multiplication was slightly decreased, and virus production was delayed by about 14 days. The highest level of resistance to HIV-1 infection was observed in MT4 cells transformed with a vector containing a fusion tk-TAR (trans activation-responsive) promoter to allow ribozyme expression in a constitutive and tat-inducible manner; no HIV-1 production was observed 22 days after infection of these cells. These results indicate that retroviral vectors expressing HIV-1 RNA-specific ribozymes can be used to confer resistance to HIV-1 infection. PMID- 1895400 TI - Sequence-specific interaction of the Ets1 protein with the long terminal repeat of the human T-lymphotropic virus type I. AB - We recently demonstrated that members of the c-ets proto-oncogene family, Ets1 and Ets2, are sequence-specific transcriptional activators of the human T lymphotropic virus type I (HTLV-I) long terminal repeat (LTR). We now report that the HTLV-I LTR contains two distinct Ets1-responsive regions, ERR-1 and ERR-2. Expression of Ets1 with reporter plasmids containing ERR-1 or ERR-2 upstream of a basal promoter resulted in an increase in transcriptional activity. By gel mobility shift assay, the interaction of Ets1 with the downstream ERR-1-binding region was found to be more stable than its interaction with the upstream ERR-2 region. By DNase I footprint, gel mobility shift, and methylation interference analyses, ERR-1 was found to contain two Ets1 binding sites, ERE-A and ERE-B. A recombinant Ets1 protein was found to bind with higher affinity to ERE-A than to ERE-B. Binding of Ets1 to these sites appears to result in a specific and sequential protection of a 37-nucleotide sequence of the HTLV-I LTR from -154 to 118. In view of the high-level expression of Ets1 in lymphoid cells, the c-ets proto-oncogenes encode transcription factors which could play an important role in both basal and Tax1-mediated HTLV-I transcription. PMID- 1895404 TI - Transcriptional and posttranscriptional regulation of class I major histocompatibility complex genes following transformation with human adenoviruses. AB - Transformation of rodent cells by human adenoviruses is a well-established model system for studying the expression, regulation, and function of class I antigens. In this report, we demonstrate that the highly oncogenic adenovirus type 12 operates at the transcriptional and posttranscriptional levels in regulating the activity of major histocompatibility complex class I genes and products in transformed cells. Adenovirus type 12 suppresses the cell surface expression of class I antigens in most cell lines. Nevertheless, in a number of cell lines suppression is the result of reduction in the amount of stable specific mRNA, while in another group of cell lines suppression involves interference with processing of a posttranscriptional product. The two mechanisms operate both for the endogenous H-2 genes and for a miniature swine class I transgene that is expressed in the cells. PMID- 1895403 TI - Defective hepatitis B virus particles are generated by packaging and reverse transcription of spliced viral RNAs in vivo. AB - Generation of replicative defective viruses is frequently observed during viral infections. We now report that encapsidation and reverse transcription of spliced viral RNA is an additional mechanism for synthesis of defective viral particles. We have investigated the in vivo synthesis of a spliced hepatitis B virus (HBV) RNA. By using the polymerase chain reaction with different sets of primers on DNA purified from infected livers and the HepG2 HBV cell line, we detected a subgenomic HBV DNA complementary to the spliced viral RNA. Its nucleotide sequence was found to be identical to that previously described for the spliced RNA. This HBV RNA is packaged and reverse transcribed in vivo, the cDNA being incorporated into circulating particles. This finding establishes the synthesis of spliced HBV RNA in vivo and indicates that its reverse transcription can give rise to defective viruses. PMID- 1895405 TI - Moloney leukemia virus immortalizes B lymphocytes in vitro. AB - An in vitro culture system in which Moloney murine leukemia virus induces immortalization of mature B lymphocytes has been developed. The cell lines derived in this way are nontumorigenic, and virus production is not required to sustain them. This system provides a new in vitro model with which to study the stepwise process of transformation by retroviruses lacking oncogenes. PMID- 1895406 TI - Molecular characterization of biologically diverse envelope variants of human immunodeficiency virus type 1 derived from an individual. AB - The envelope genes of six viruses derived from a single sampling from an individual chronically infected with human immunodeficiency virus type 1 (RJS-4) have been analyzed. Here we present the nucleotide and predicted amino acid sequences of these variants and show a correlation between biological properties and disturbance of the envelope reading frame. PMID- 1895407 TI - Recovery of infectious human immunodeficiency virus type 1 after fusion of defectively infected clones of U-937 cells. AB - Polyethylene glycol was used to induce polykaryon formation among U-937 cell subclones carrying defective human immunodeficiency virus (HIV) type 1 proviral DNA. Fusion of cells which produced gp120-defective virions (UHC15.7) with cells unable to generate reverse transcriptase (RT) activity (UHC8 and UHC18) yielded polykaryons which made infectious viral progeny that showed normal protein profiles. Southern blot analysis of proviral DNA of cells infected with such fusion-derived virus revealed a restriction map identical to that of cells harboring infectious parental-type HIV type 1 (U-937/UHC1). These results suggest that repair mechanisms involving genetic recombination(s) play a role in the generation of infectious virus after fusion of cells which harbor defective HIV. PMID- 1895408 TI - Disturbance of nuclear transport of proteins in CD4+ cells expressing gp160 of human immunodeficiency virus. AB - An extensive cytopathic effect occurred in the CD4+ cells expressing gp160 of human immunodeficiency virus. A protein capable of nuclear location that was microinjected into such cells was not transported into the nuclei at an early stage when little cytopathic effect had yet to occur. PMID- 1895410 TI - Retraction. Functional and nonfunctional measles virus matrix genes from lethal human brain infections. PMID- 1895409 TI - Substrate specificity of recombinant human immunodeficiency virus integrase protein. AB - Recombinant human immunodeficiency virus type 1 (HIV-1) integrase (IN) produced in Escherichia coli efficiently cleaves two nucleotides from the 3' end of synthetic oligonucleotide substrates which mimic the termini of HIV-1 proviral DNA. Efficient cleavage was restricted to HIV-1 substrates and did not occur with substrates derived from other retroviruses. Mutagenesis of the U5 long terminal repeat (LTR) terminus revealed only moderate effects of mutations outside the terminal four bases of the U5 LTR and highlighted the critical nature of the conserved CA dinucleotide motif shared by all retroviral termini. Integration of the endonuclease cleavage products occurs subsequent to cleavage, and evidence that the cleavage and integration reactions may be uncoupled is presented. Competition cleavage reactions demonstrated that IN-mediated processing of an LTR substrate could be inhibited by competition with LTR and non-LTR oligonucleotides. PMID- 1895411 TI - Temporarily implanted urethral coil stent for the treatment of recurrent urethral strictures: a preliminary report. AB - A new urethral stent developed for use in recurrent urethral strictures is presented. This metallic coil is self-expanding when released from its introducing catheter. The stent was used in 18 patients with recurrent strictures necessitating frequent dilation or urethrotomy. The stent is introduced under fluoroscopic guidance after internal urethrotomy or simple dilation. Strictures of 5 to 60 mm. were treated successfully with this device. All strictures were distal to the external sphincter. No serious complications attributed to the device were recorded. When necessary, the stent could be repositioned either under fluoroscopic control or endoscopically. This device can hold the stenotic area of the urethra open for long intervals allowing for complete healing. Even after 6 months the stent is not covered with urethral epithelium and does not become incorporated into the urethral wall. It can be removed easily without an operation by simple manipulation. The large internal caliber permits passage of endoscopes up to 17F in patients who require cystoscopy. The device can be removed before transurethral resections and then a new stent can be inserted at the end of the procedure. Mean followup of our patients with the stent indwelling was 8 months (range 4 to 11 months). Followup after removal of the stent (6 patients) was 3 to 8 months (mean 5 months). The patients voided well during followup and were fully continent. No incrustations were noted in the removed stents even after 6 months and no stent became obstructed due to tissue proliferation or incrustation. In 1 patient the stricture recurred after 3 months and a new stent was inserted. Urine sterilization was obtained in 7 patients with infected urine after relatively short courses of antibiotics. This stent seems to be a promising tool for the nonoperative treatment of recurrent urethral strictures. PMID- 1895412 TI - Management of persistent or recurrent urinary incontinence after placement of artificial urinary sphincter. AB - A rational systematic approach is presented in the evaluation of 14 men with persistent or recurrent urinary incontinence after placement of the AMS800 artificial urinary sphincter. Mechanical malfunctions, including device leaks and control assembly malfunctions, may often be discovered with physical examination and radiographic evaluations. Nonmechanical malfunctions, such as cuff erosion, inadequate cuff compression and functional urethral atrophy, can be diagnosed with perfusion sphincterometry, urethroscopy and a filling cystometrogram, all combined in 1 simplified technique. With the presented algorithm the over-all success rate after 1 revision was 82%. Mechanical malfunctions appear to have a better revision rate of success than nonmechanical malfunctions (100% versus 71.5%, respectively). PMID- 1895413 TI - The incidence of Peyronie's disease in Rochester, Minnesota, 1950 through 1984. AB - Peyronie's disease was diagnosed in 101 male residents of Rochester, Minnesota between 1950 and 1984. Mean patient age at diagnosis was 53 years. The average age-adjusted annual incidence rate of 25.7 and a prevalence rate of 388.6 per 100,000 male population were noted. The steady increase in incidence with time may reflect an increasing tendency to obtain medical help. However, the possibility of a true increase in the incidence rate cannot be ruled out. An effort was made to identify possible risk factors and other disease associations. Rheumatoid arthritis and hypertension were more common among the patients compared to the Rochester population. In contrast, no excess of diabetes mellitus was observed among patients with Peyronie's disease. PMID- 1895414 TI - Calcitonin-gene-related peptide: a possible role in human penile erection and its therapeutic application in impotent patients. AB - A functional study was done to examine a possible role of calcitonin-gene-related peptide in human penile erection and its possible therapeutic applications for patients with erectile dysfunction. In the determination of an effective dosage, 5 ng. (2 patients), 50 ng. (2 patients), 500 ng. (4 patients), 5 micrograms (4 patients) and 25 micrograms (7 patients) were injected intracavernously, and pulse and blood pressure were monitored. Arterial inflow was measured by Doppler sonography, smooth muscle relaxation was determined by the analysis of cavernous electrical activity and cavernous outflow occlusion was recorded by cavernosometry. In 12 patients the erectile response of prostaglandin E1 was compared to the response of an equal (6 patients) or decreased dose of prostaglandin E1 combined with an equal weight of calcitonin-gene-related peptide. In 14 patients the erectile response to the combination of calcitonin gene-related peptide and prostaglandin E1 was compared to the response of prostaglandin E1 alone, and with a combination of 15 mg./ml. papaverine and 0.5 mg./ml. phentolamine. Calcitonin-gene-related peptide induced an increase in the penile arterial inflow, cavernous smooth muscle relaxation and cavernous outflow occlusion. Histochemical results indicated nerve fibers positive for calcitonin gene-related peptide within the cavernous bodies. A dose-dependent erectile response to calcitonin-gene-related peptide was observed at doses of 500 ng. to 25 micrograms. Systemic side effects were first observed at a dose of 25 micrograms in 2 of 7 patients. The combination of calcitonin-gene-related peptide and prostaglandin E1 was more effective in inducing a full erection than either prostaglandin E1 alone or the combination of papaverine and phentolamine. Pain was reported in 4% of the patients who received the combination of calcitonin gene-related peptide and prostaglandin E1, whereas 42% of those who received prostaglandin E1 alone reported pain. Our results suggest that calcitonin-gene related peptide may be a possible neurotransmitter for penile erection. A combination of calcitonin-gene-related peptide and prostaglandin E1 seems to be an effective alternative combination in the treatment of impotence. PMID- 1895415 TI - Computerized analysis of smooth muscle fibers in potent and impotent patients. AB - Reduction or dysfunction of the intracavernous smooth muscle fibers can provoke impotence. Computerized digital image analysis of corpus cavernosum biopsies was performed in potent and impotent patients to quantify the percentage of smooth muscle fibers. In 5 normal patients the smooth muscle area represented 40 to 52% of the specimen, in 20 patients with cavernous dysfunction it was 10 to 36% and in 10 patients with arterial disease it was 13 to 25%. This method appears to be important to understand better certain mechanisms of impotence and to approach the potential treatment. PMID- 1895416 TI - Changes in penile sensitivity following papaverine-induced erection in sexually functional and dysfunctional men. AB - To understand more clearly the role of penile sensitivity in sexual functioning, changes in penile thresholds resulting from papaverine-induced tumescence were studied in men who were either sexually functional or suffering from erectile dysfunction. Variable vibratory tactile stimulation was applied to 2 different sites, the base and tip of the underside of the penis. With standard psychophysical methodology, subjective thresholds were determined from a minimum of 5 threshold crossings. Results indicated a significant elevation in threshold after intracavernous papaverine injection, even though only partial erection was induced in most subjects. Men with erectile dysfunction had higher thresholds than control subjects but no difference in sensitivity was found between the base and tip of the penis. These findings indicate that low penile sensitivity is characteristic of some, although not all, men experiencing erectile problems and that this sensitivity is even lower during tumescence. PMID- 1895417 TI - Pharmacologically induced erections among geriatric men. AB - Intracavernous injection of vasoactive drugs for the treatment of erectile impotence has become a standard therapeutic technique. Previous reports detailing experience with this treatment are based on patient populations significantly younger than most patients who suffer from impotence. The geriatric population, which comprises the majority of patients with importance, is unique due to the physical, psychological and social changes associated with the aging process. To characterize better elderly men with impotence, and determine whether intracavernous injection therapy is safe and effective in this age group, a retrospective analysis was performed upon patients attending the male sexual dysfunction clinic at our university medical center who received a standard papaverine and phentolamine mixture (30 mg. papaverine and 1.0 mg. phentolamine per ml.). The etiology of impotence, degree of patient satisfaction and complication rate of 65 patients 65 years or older (mean age 70 years) undergoing papaverine plus phentolamine self-injection therapy were compared to a similar size group of impotent men approximately 20 years younger (mean age 47 years). Significant differences in etiology of impotence were evident between the 2 groups. Treatment response rates were equal for the 2 age groups although elderly patients required a higher dose of papaverine and phentolamine to obtain an erection, and used the medication less frequently. Complications were few, of minimal consequence and occurred with equal frequency between the 2 age groups. PMID- 1895418 TI - The outcome of prostatectomy on chronic retention of urine. AB - A total of 68 men with bladder outflow obstruction and chronic retention (residual urine greater than 300 ml.) underwent investigation before and after prostatectomy with medium fill cystometry and natural fill long-term bladder pressure monitoring. Postoperatively, upper tract dilatation (present in 28 men preoperatively) resolved in all but 2 men and serum creatinine levels improved significantly. Irritative and obstructive symptom scores improved postoperatively (p less than 0.00006), although 17% of the men still had significant symptoms. Residual urine volumes decreased and flow rates improved (p less than 0.00006) but 32% of the men still had a residual urine of greater than 200 ml. Urodynamic parameters improved during medium fill cystometry and long-term monitoring. The main risk factors for upper tract dilatation are a pressure increase during bladder filling on conventional cystometry and the frequency of phasic detrusor activity during long-term monitoring, and they decreased postoperatively. PMID- 1895419 TI - Cell kinetics by bromodeoxyuridine labeling and deoxyribonucleic acid ploidy in prostatic carcinoma needle biopsies. AB - We studied 63 prostate carcinomas in needle biopsies after labeling in vitro by incubating the entire biopsy specimen with tritiated thymidine or bromodeoxyuridine before fixation. Biopsies from 176 patients were labeled, of which 98 were benign and 78 were carcinomas (15 carcinomas were excluded because of scant tissue). The procedure did not interfere with histological diagnosis. Median labeling index was 0.87% (range 0.1 to 29.3%). A labeling index exceeding 3% was unusual but it may indicate the potential for rapid clinical progression. Deoxyribonucleic acid (DNA) flow cytometry was performed on the last 44 carcinomas using cells shed by the prostatic needle biopsy tissue samples during transportation to the pathology laboratory. A sufficient number of cells were obtained for analysis in 37 cases, of which 6 were DNA aneuploid. Labeling index correlated with Gleason histological grade and score, and data from the 6 DNA aneuploid carcinomas suggest association between DNA aneuploidy and a high labeling index. Estimates of percentage of S-phase cells by flow cytometry did not correlate with variables other than DNA index, and appear to have been affected by a high noise-to-signal ratio (few proliferative cells relative to cellular debris) and inability to discriminate between benign and carcinomatous cells. PMID- 1895420 TI - The risk of dying of prostate cancer in patients with clinically localized disease. AB - From 1966 to 1979, 360 patients with clinical stages A2, B and C1 prostate cancer underwent staging pelvic lymphadenectomy, and completed a course of combined interstitial radioactive gold seeds and external beam radiotherapy. All patients had a normal serum prostatic acid phosphatase level and a bone scan negative for metastases. All patients were followed until death or for a mean of 7.3 years (range 1.2 to 18.25 years) for those alive at analysis. To determine the risk of dying of prostate cancer we reviewed the records of the 142 patients (39%) who died. At analysis 21% of the patients had died of prostate cancer and 17% of other known causes. The cause of death could not be determined in 4 patients (1%). Cardiovascular disease accounted for a fifth of all deaths. The actuarial risk of death of prostate cancer for all patients was 8 +/- 3% (+/- 2 standard errors) at 5 years and 30 +/- 7% at 10 years. The risk of death of all causes was 16 +/- 4% at 5 years and 46 +/- 7% at 10 years. An increased risk of cancer death was associated with established risk factors, including advanced local disease, poorly differentiated histology, pelvic nodal metastases and distant recurrence. We also noted a substantial risk of cancer death in patients who had local tumor recurrence. While previous studies have reported a relatively low incidence of cancer deaths (4 to 17%) in patients initially diagnosed with localized disease, our data suggest that prostate cancer is the major cause of mortality in such patients. Aggressive curative therapy, regardless of treatment modality, should be considered for localized prostate cancer in men with a life expectancy of 10 or more years. PMID- 1895421 TI - Radical prostatectomy for stage A adenocarcinoma of the prostate: staging errors and their implications for treatment recommendations and disease outcome. AB - Of 148 patients with clinical stage A1 (32) or A2 (116) disease who had radical prostatectomy only 63% and 62%, respectively, had pathological stage A disease. Although 25% of those with clinical stage A1 and 9% of those with clinical stage A2 disease had no cancer at radical prostatectomy, 12% and 29%, respectively, had pathological stage C disease or higher. Clinical Mayo grade 1 was never associated with extracapsular disease but 60% of those with grade 3 or higher tumor did have extracapsular disease. Over-all survival was comparable to the expected survival. Clinical stage A2 cancer was associated with a significantly higher progression rate (when prostate specific antigen values were considered, p = 0.0011) and cancer death rate (p less than 0.045) than stage A1 disease, whereas pathological stage was not significantly related to disease outcome, possibly because of the use of adjuvant treatment (hormonal or radiation) for some patients with pathological stage C or higher disease. The vagaries of clinical staging associated with stage A disease, as well as the previously documented progression on long-term followup (8 to 10 years) in younger (60 years old or less) patients with stage A1 prostate cancer make radical prostatectomy with its limited morbidity an acceptable treatment choice. PMID- 1895422 TI - Can stage A1 tumor extent be predicted by transurethral resection tumor volume, per cent or grade? A study of 64 stage A1 radical prostatectomies with comparison to prostates removed for stages A2 and B disease. AB - We studied 64 totally embedded radical prostatectomy specimens of stage A1 prostate cancer. The transurethral resection specimens were studied and compared to previously studied stages A2 and B cancer in which tumor volumes also were calculated. At radical prostatectomy 6% of the specimens had no residual cancer, 74% had minimal cancer and 20% had substantial cancer. Although most stages A2 and B tumors were larger, there was overlap among all stages. Transurethral resection tumor volume, per cent and grade were not statistically correlated with either radical prostatectomy residual tumor volume, or whether tumor was classified as minimal or substantial. Gleason sum 2 to 4 versus 5 to 7 tumor on transurethral resection showed no difference in predicting radical prostatectomy residual tumor or minimal versus substantial tumor status. Because 20% of all stage A1 cancers have substantial tumor at radical prostatectomy unpredictable by transurethral resection, radical prostatectomy remains an option for young men with stage A1 prostate cancer. PMID- 1895423 TI - A comparison of the morphological features of cancer arising in the transition zone and in the peripheral zone of the prostate. AB - To determine the characteristics of transition zone and peripheral zone prostate cancer, we examined a series of 42 stage A and 54 stage B radical prostatectomy specimens with particular attention to the number of separate foci of cancer, zone of origin, volume and grade of each focus, and presence of severe intraductal dysplasia (high grade prostatic intraepithelial neoplasia), extra capsular extension and seminal vesicle invasion associated with cancer in each zone. We found that there were fundamental differences between transition zone and peripheral zone cancers, and that the features that characterize these tumors were apparent in stages A and B disease. Although the total tumor burden was similar in stages A (3.98 cc) and B (4.56 cc) disease, stage A cancer tended to be multifocal (3.1 tumors per prostate) and more diffuse. While 81% of stage A prostate specimens contained a tumor of transition zone origin and 93% had cancer of peripheral zone origin, transurethral resection of the prostate sampled a transition zone cancer in 77% and a peripheral zone cancer in 31% (8% had both types). Stage B cancer tended to be more focal (2.3 cancers per prostate). All stage B prostate specimens contained a peripheral zone cancer and 43% had a transition zone cancer as well. In only 1 stage B cancer patient was the transition zone tumor the palpable or index cancer. In stages A and B disease, peripheral zone tumors were less well differentiated (median Gleason sum 6 and 7) than transition zone tumors (5 and 5, respectively) and more likely to extend through the capsule (44% versus 11%). Seminal vesicle invasion arose from 19% of the peripheral zone but none of the transition zone cancers. Peripheral zone tumors were almost always (93%) associated with high grade prostatic intraepithelial neoplasia, while none of the transition zone cancers was so associated. For peripheral zone disease there was a moderate correlation between volume and grade (tau = 0.46, p less than 0.001) so that the larger the tumor the higher the Gleason sum but within transition zone disease this correlation was poor (tau = 0.23) and not statistically significant (p greater than 0.05). Extracapsular extension occurred at a smaller volume with peripheral zone cancer (mean 3.86, minimum 0.06 cc) than transition zone cancer (mean 4.98, minimum 0.39 cc). Cancer that arises in the transition zone appears to have a different histogenesis, is associated with more favorable pathological features and may have less malignant potential than tumors that arise in the peripheral zone. PMID- 1895424 TI - Pararectus retroperitoneal radical nephrectomy. AB - We describe a new pararectus retroperitoneal approach to the kidney, which allows easy identification and occlusion of the renal vessels before mobilization of the kidney. This approach potentially reduces morbidity, hospital stay and cost. The technique has been used in 4 cases of radical nephrectomy for tumor and in 1 for pyonephrosis. PMID- 1895425 TI - Prostatic needle biopsy using an Iowa trumpet biopsy needle guide during standard digital rectal examination: a comparison with ultrasound controlled biopsy. AB - A new method of transrectal biopsy of the prostate using an Iowa trumpet is introduced. This method allows the urologist to biopsy what he or she palpates during a standard digital rectal examination. The methodology of using this biopsy guide is explained. Among 66 patients with a palpable prostatic abnormality 31 cancers were diagnosed with this new method, while only 15 cancers could be diagnosed with standard ultrasound guided biopsy techniques. However, of these 31 cancers 8 would have been missed without the aid of ultrasound. No unusual complications were noted with this new biopsy method. PMID- 1895426 TI - Failed bladder neck reconstruction: options for management. AB - During the last 10 years 17 patients have been seen at this institution for persistent urinary incontinence after Young-Dees-Leadbetter bladder neck reconstruction. Of these patients 16 were born with classical bladder exstrophy and 1 with complete epispadias. Six patients underwent 1, 10 underwent 2 and 1 underwent 3 prior bladder neck procedures. As salvage procedures 8 patients underwent another Young-Dees-Leadbetter procedure, 1 repeat bladder neck reconstruction and augmentation cystoplasty, 3 augmentation alone, 4 bladder augmentation with creation of a continent abdominal stoma and 1 augmentation with implantation of an artificial urinary sphincter. Of the 8 patients who underwent a repeat Young-Dees-Leadbetter procedure 7 are dry for 3 hours or more and 1 is dry for greater than 3 hours on intermittent self-catheterization. All of those who are dry for greater than 3 hours are dry at night and 1 wears pads when engaging in strenuous physical activity. Of the 9 patients who underwent augmentation cystoplasty along with other adjunctive procedures 8 are continent for greater than 3 hours on intermittent catheterization, 6 are dry at night if they perform catheterization at bedtime and 1 remains totally incontinent after removal of the artificial urinary sphincter. Thus, with persistence and creativity a child with a previously failed bladder neck reconstruction or even multiple failed repairs can be made socially continent, providing a satisfactory alternative without resorting to urinary diversion. PMID- 1895427 TI - Development of the human anterior urethra. AB - To further our understanding of the development of the anterior urethra a series of 38 normal human fetuses ranging from the end of the embryonic period proper to the third trimester of gestation were studied. Tissues prepared as serial histological sections were examined and appropriate specimens were reconstructed. The formation of the bulbar and spongy urethra occurred by proliferation of mesenchyme underlying the epithelium of the urethral folds, causing the creation of a tubular urethra by epithelial fusion in the ventral midline. The tubular urethra becomes invested by mesenchyme, the future corpus spongiosum. This process of fusion of the urethral folds extends to the glans penis. At this period of development the glans contains the urethral plate, a lamina of epithelium lacking a lumen. The mechanism of the subsequent connection of the spongy urethra to the canalized urethral plate has been the point of controversy. Our observations support the idea that 3 processes must act in synchrony to produce successful completion of the anterior urethra: 1) the prepuce forms by overgrowing the glans due to proliferation of the penile skin and subcutaneous tissues, and in so doing it continues the progression of closure of the urethral folds into the glans and forms the frenulum by its fusion on the ventral aspect, 2) the mesenchyme surrounding the prolongation of the urethra fuses with the mesenchyme of the glans, which before this time had existed as a mesenchymal structure distinct from the corpus spongiosum or corpus cavernosum and 3) the epithelium of the urethral plate within the glans, which underlies the epithelial tag, becomes canalized and develops continuity with the lumen of the spongy urethra. PMID- 1895428 TI - Clinical outcome of fetal uropathy. I. Predictive value of prenatal echography positive for obstructive uropathy. AB - Clinical followup was performed in 73 neonates with a prenatal echographic suspicion of uropathy. Of 42 patients with a prenatal suspicion of unilateral hydronephrosis only 15 had pathological obstruction and 2 had multicystic dysplastic kidneys. Among 10 infants with a prenatal suspicion of bilateral hydronephrosis only 1 had true bilateral obstruction and 2 had unilateral obstruction. In 2 patients hydroureteronephrosis seen on prenatal echography was due to massive bilateral vesicoureteral reflux. In this group there was also a multicystic dysplastic kidney and 1 patient with bilateral cystic dysplasia. There was a prenatal suspicion of cystic disease in 8 infants. Postnatally, diagnosis was multicystic dysplastic kidney in 2 patients and a simple renal cyst in 4. The remaining 2 neonates had obstructive uropathy. Finally, of 13 neonates with a prenatal suspicion of anatomical-echo-structural abnormalities a definitive abnormality could be established in only 8. The predictive value of prenatal echography positive for obstructive uropathy was 34.6%. PMID- 1895429 TI - Clinical outcome of fetal uropathy. II. Sensitivity of echography for prenatal detection of obstructive pathology. AB - Among 8,579 neonates born between February 1, 1981 and March 31, 1987, and cleared by prenatal sonography for significant urinary tract abnormality 158 subsequently were hospitalized because of signs or symptoms of urinary tract disease, predominantly urinary tract infection. Evaluation of these 158 patients revealed 24 with vesicoureteral reflux, 7 with duplicated systems (2 of which showed reflux), 1 with the syndrome of Fraley, 1 with pyelectasis and 5 with mild hydronephrosis (3 secondary to reflux and 2 with diethylenetriaminepentaacetic acid renal scans considered to be nonobstructed). There was no incidence of significant obstructive uropathy that had been missed by the previous prenatal sonography and that surfaced subsequently to cause morbidity in this series. The principal disorder of the urinary tract that may fail prenatal investigation is vesicoureteral reflux. PMID- 1895430 TI - Preperitoneal approach for hernia repair: clinical application in pediatric urology. AB - The preperitoneal approach for inguinal hernia repair rarely is indicated in children. However, we report on its clinical usefulness for children in whom the perivesical space must be exposed, such as during surgical repair of bladder exstrophy, ureterocele and ureteral reimplantation. This approach allows for a true high ligation of the hernia sac, and the repair is safe, fast and effective. PMID- 1895431 TI - Primary angiosarcoma of adrenal gland presenting as paraneoplastic syndrome: case report. AB - Angiosarcoma is an uncommon neoplasm that rarely involves the adrenal gland. We report on a patient with primary angiosarcoma of the adrenal gland who presented with symptoms best characterized as a paraneoplastic syndrome. PMID- 1895433 TI - Hydroureteronephrosis secondary to perforated Meckel's diverticulum. AB - Complications related to Meckel's diverticulum are not unusual. However, involvement of the urinary tract is extremely rare. To our knowledge this is the first reported case of ureteral obstruction due to perforation of Meckel's diverticulum. PMID- 1895432 TI - Celiac axis and superior mesenteric artery injury associated with left radical nephrectomy for locally advanced renal cell carcinoma. AB - The superior mesenteric artery and celiac axis were inadvertently ligated during left radical nephrectomy for a large upper pole renal carcinoma with massive perihilar and periaortic adenopathy. Computer-generated 3-dimensional illustrations created from the computerized tomography scan demonstrated the close proximity between these visceral branches and the adenopathy mass complex, and showed how this bulky disease may interfere with surgical anatomy. When left radical nephrectomy is performed for locally advanced and/or bulky node-positive renal neoplasms, surgeons must be cognizant of the location of the major visceral arterial branches and possible anatomical distortions. PMID- 1895434 TI - Successful term delivery by cesarean section in a patient with a continent ileocecal urinary reservoir. AB - Childbirth in a mother with a continent urinary reservoir to our knowledge has not been previously reported. The effects of the gravid uterus on the reservoir are presented, as well as management of the pregnancy and delivery. PMID- 1895435 TI - Mast cell infiltration in intestine used for bladder augmentation in interstitial cystitis. AB - Two patients with histologically confirmed interstitial cystitis underwent bladder augmentation procedures (clam cystoplasty and Mainz pouch cystoplasty) because of therapy resistant low abdominal pain and decreased functional bladder capacity. However, symptoms of low abdominal pain and urinary retention (1 patient) persisted, and cystectomy was performed in both patients after 14 and 20 months, respectively. Histological examination of the specimens showed changes in the intestinal areas of the augmented bladder, resembling interstitial cystitis. The etiology of this phenomenon and the possible role of intestinal interstitial cystitis in augmentation failures are discussed. PMID- 1895436 TI - Colovesical fistula secondary to vesical gangrene in a diabetic patient. AB - We present a case of colovesical fistula secondary to vesical gangrene. Precipitating factors were diabetes and vesical distension caused by the obstruction of an indwelling catheter. This complication is an exceptional outcome in gangrenous cystitis and it requires emergency surgical treatment. PMID- 1895437 TI - A case of granulomatous hepatitis after intravesical bacillus Calmette-Guerin administration. AB - A 61-year-old man received intravesical bacillus Calmette-Guerin (BCG) as treatment for superficial bladder carcinoma. High spiking relapsing fevers began 39 days after the initial treatment. A liver biopsy revealed noncaseating granuloma. Deoxyribonucleic acid hybridization of the bone marrow was positive for Mycobacterium tuberculosis complex. Pressure exerted to instill the BCG may have favored dissemination. PMID- 1895438 TI - The neodymium:YAG laser recanalization in a patient with azoospermia due to ejaculatory duct agenesis. AB - A 32-year-old man with azoospermia is presented. Transperineal echographically guided vesiculography of the vas deferens showed absence of the ejaculatory duct and presence of a cystic mullerian duct in which both enlarged seminal vesicles joined. Transurethrally, by means of a contact tip over the verumontanum a new channel was created by neodymium:YAG laser irradiation at 25 watts every 2 seconds. The patient had 32.10(6) spermatozoa per ml. with good quality on semen analysis 10 months later. PMID- 1895439 TI - Simultaneous ipsilateral vasal and epididymal reconstruction. AB - Injuries to the spermatic cords, sustained during childhood inguinal hernioplasty, caused unilateral testicular atrophy, multiple bilateral excurrent duct obstruction and aspermia. Simultaneous unilateral vasal reconstruction and vaso-epididymostomy resulted in satisfactory semen parameters. It is expected that vasal integrity will be maintained after multiple reconstructive procedures at different locations if further injury to the vascular supply of the excurrent duct is avoided. PMID- 1895440 TI - SCID mice: a suitable model for experimental studies of urologic malignancies. AB - In vivo studies on human malignant tumors are limited because of a lack of suitable animal models. In this study, the usefulness of SCID (severe combined immunodeficiency) mice, deficient in functions of both T- and B-lymphocytes, was evaluated. Inbred SCID mice were kept in isolated cages and 2 x 10(7) cells of KU 7, an established bladder carcinoma cell line, were inoculated in the subcutaneous tissue of the flank region of six SCID mice. Athymic nude mice were inoculated by the same method and served as the controls. The KU-7 cells were taken within 14 days in the injected region in all six SCID mice, while in only five out of eight nude mice. Tumors subsequently formed at the site of inoculation in these mice were confirmed to be transitional cell carcinomas histologically and intra-abdominal metastases were noted in two SCID mice. We conclude that SCID mice provide an ideal in vivo model for experimental studies of human urologic malignant tumors. PMID- 1895441 TI - Proteus mirabilis biofilm protection against struvite crystal dissolution and its implications in struvite urolithiasis. AB - Proteus mirabilis biofilm formation, struvite (MgNH4PO4.6H2O) crystal formation and dissolution in an artificial urine mixture were monitored using computer enhanced microscopy (CEM) and a 1 x 3 mm. glass flow cell. Image analysis showed that P. mirabilis biofilm formation did not occur to any extent at macroenvironment flow rates greater than two mL/h (equivalent to a microenvironment flow rate of less than 5 microns./sec). Essentially, cells attached to glass surfaces, grew slowly and divided. Daughter cells were generally released directly into the medium where they could then presumably colonize other regions. Microcolonies formed by the adhesion of aggregates of cells from the medium, and over time grew into biofilms. Struvite crystallization due to urease activity and pH elevation above neutrality, was preceded by the deposition of organic matter on the glass surface, followed by the appearance of a number of tiny (one to two microns.) crystals. Crystals forming within a biofilm at low dilution rates took on a characteristic twinned or "X-shaped" appearance (crystal habit) indicative of a rapid growth rate. Those forming outside the biofilm took on a more tabular appearance reflecting their slower growth. When the macroenvironment flow rate of artificial urine (initial pH 5.8) in the glass flow cell was increased from two mL/h to four mL/h, struvite crystals not associated with biofilms dissolved within five to 10 min. Crystals entrapped within the P. mirabilis biofilm withstood flow rates up to 200 mL/h presumably due to the maintenance of an alkaline Mg-saturated microenvironment within the biofilm. These observations may suggest a mechanism by which struvite calculi can grow in spite of neutral or acidic urine pH and resist mild acidification therapy. PMID- 1895442 TI - Treatment of the Dunning prostate rat tumor R3327-AT1 with pulsed high energy ultrasound shock waves (PHEUS): growth delay and histomorphologic changes. AB - We are interested in the interaction of pulsed high energy shock waves (PHEUS) on soft tissues treated in situ to evaluate its potential for therapeutic use. The experimental apparatus built by us was adapted from a lithotripter designed for clinical use. For the present studies we used the R3327-AT1 Dunning prostate tumor growing s.c. in the thigh of Copenhagen rats. The treatments consisted of four groups of eight animals each who received 500 or 2000 pulses at 1 or 5 Hz. Sham-treated tumor bearing animals served as controls (n = 11). During each PHEUS treatment, petechial bleeding of the skin at the point of entry and exit of sound appeared. Sonication at a repetition rate of five Hz seemed to induce more macroscopic damage in terms of hematomas and skin effects. The cytotoxic effects of PHEUS to tumor tissue were sufficient to induce a significant delay (p less than 0.05) in tumor growth but no clear-cut dose relationship was established. Histological studies revealed widespread early rupture of the fine vasculature with extravasation of erythrocytes. By 72 hr., in PHEUS treated tumors, a large necrosis was seen within the central zone which was never observed in sham treated tumors. Our results clearly indicate that PHEUS has a cytotoxic potential. The observation of a rapid onset of hemostasis, stark hemorrhage and necrosis in the treatment field would suggest that vascular damage is an important contributing factor. PMID- 1895443 TI - Regional chemotherapy using continuous intravesical infusion doxorubicin for the treatment of muscle invasive transitional cell bladder carcinoma in a rat model. AB - Previously established animal models of invasive transitional cell bladder carcinoma and continuous infusion intravesical drug delivery were combined to evaluate the urothelial toxicity and antineoplastic efficacy of continuous intravesical infusion doxorubicin (DOX). Dose-response toxicity experiments studied histologic changes in the rat urinary bladder following urothelial exposure to three different urinary levels of DOX, as a function of the duration of drug infusion. Systemic and local drug absorption, as measured by DOX levels in serum, bladder, retroperitoneal lymph nodes, and liver, was measured at intervals during drug administration. In vitro chemosensitivity assays were used to determine tumor sensitivity to DOX. Treatment studies evaluated the impact of 14-day continuous infusion DOX beginning seven days following tumor implantation. No histologically discernable changes in the normal urothelium were noted in bladders of animals receiving continuous intravesicle DOX at mean urinary concentrations of 0.05 micrograms./ml. (n = 5), 0.56 micrograms./ml. (n = 10), and 5.69 micrograms./ml. (n = 10) for periods of up to 14 days. Serum drug concentrations demonstrated a non-significant upward trend following the start of therapy. Significant increases in tissue DOX levels were noted in the bladder and retroperitoneal lymph nodes on chemotherapy days 7 and 14. Mean tissue DOX concentrations in both the bladder and lymph nodes were greater than the IC50 observed in the in vitro sensitivity assay. DOX-treated tumor-bearing animals (n = 17) had a mean tumor volume (+/- standard deviation) of 0.65 gm. +/- 0.52 gm. compared to an average tumor volume of 1.20 gm. +/- 0.66 gm. in the control group (n = 18) (p = 0.0112). Continuous infusion intraluminal chemotherapy demonstrated a clear cytoreductive effect with minimal local toxicity in this model. Drug tissue levels were observed in regional lymphatic drainage fields as well as the bladder wall. Further study to evaluate this approach as a bladder-sparing alternative to muscle invasive disease is warranted. PMID- 1895444 TI - Acquired cystic disease of the kidney analyzed by microdissection. AB - Four cases of acquired cystic disease of the kidney (ACDK) were studied by the microdissection technique (MD) of Darmady and Baert to analyze the cystic transformation. No patient had a history or clinical evidence of the adult polycystic disease of the kidney (APDK). Hypothetical models related the pathogenesis of cystic transformation to either obstructive or degenerative factors. Microdissection was performed in four nephrectomy specimens of hemodialyzed patients and a total of 155 nephrons were isolated. The atrophy of the glomeruli has already been described histopathologically but MD demonstrated the existence of nephrons consisting of sclerotic glomeruli and enlarged segments between the atrophic convoluted proximal and distal tubules. Diverticula and cysts were located, above all along the proximal (mainly dilated) convoluted tubules: they were always in continuity with the tubules. Phase contrast microscopy showed a patent lumen in 80% of the proximal and distal convoluted tubules, and a regular lining of the cysts. These data support the hypothesis that ACDK is the result of hyperplasia and dilation of remaining nephrons, rather than a result of obstruction and/or fibrosis. PMID- 1895445 TI - Effects of interferon beta ser and transforming growth factor beta on prostatic cell lines. AB - The effect of interferon beta ser (IFN beta ser) on the growth of three prostatic cancer cell lines DU-145, PC-3 and LNCaP was studied. IFN beta ser inhibited growth of anchorage dependent semiconfluent monolayers and anchorage dependent colony formation of both DU-145 and PC-3 in a dose dependent manner but had no effect on LNCaP. Transforming growth factor beta (TGF beta 1) inhibited proliferation of DU-145 and PC-3 cells in 1% but not 8% fetal calf serum. The combination of TGF beta 1 and IFN beta ser was additive in its effects on growth. Neither epidermal growth factor (EGF) nor transforming growth factor alpha (TGF alpha) reduced the antiproliferative effect of IFN beta ser on these cells. These antiproliferative effects were reproduced in studies on primary epithelial cell cultures derived from prostate specimens with various pathologies. The potential use of IFN beta ser in combination with hormonal therapy to delay the development of hormone refractory tumors is discussed. PMID- 1895446 TI - Effect of in utero vesicostomy on pulmonary hypoplasia in the fetal lamb with bladder outlet obstruction and oligohydramnios: a morphometric analysis. AB - A model of early gestation bladder outlet obstruction and oligohydramnios in the fetal lamb is characterized by small, immature lungs (pulmonary hypoplasia). The current study examines how in utero relief of urinary tract obstruction produced early in gestation modifies pulmonary hypoplasia. Bladder obstruction was created at 60 days gestation in fetal sheep (term = 140 days); 11 fetuses then underwent in utero decompression at 95 to 100 days; six were left obstructed. Five normal fetuses served as controls and two underwent sham obstruction and vesicostomy. All were delivered and sacrificed near term (135 days), the right lung was inflation-fixed and its volume determined. Relative volumes of alveoli, alveolar ducts, and tissue, alveolar surface area, and alveolar numerical density were estimated morphometrically. Kidneys were examined histologically. In all animals persistent bladder obstruction produced oligohydramnios. Bladder obstruction to term produced pulmonary hypoplasia with a mean right lung volume-to-body weight ratio (LV:BW) of 14.3 cc./kg. (normal = 36.4, p less than 0.001). Structural immaturity was evidenced by an airspace fraction of only 57% (normal = 68%, p less than 0.05). Kidneys in these animals were not dysplastic; there was hydronephrosis or evidence of spontaneous urinary decompression. In eight of the 11 animals, decompression improved the LV:BW ratio to 28.4 cc./kg. (vs. obstructed, p less than 0.001; vs normal, p less than 0.05) and normalized maturity. All had increased amniotic fluid at delivery; kidneys in 7/8 animals were normal, and the other had moderate hydronephrosis. One of the 11 animals had normal kidneys, oligohydramnios, immature lungs, but with normal volume. Oligohydramnios was present in the other two of 11 fetuses despite successful decompression and they had markedly dysmorphic kidneys and profoundly hypoplastic and immature lungs (LV:BW 5.1 cc./kg.). Even after 35 days (25% gestation) of obstruction, in utero urinary tract decompression permits better lung growth and maturation than in persistently obstructed animals. The degree of renal damage from obstruction appears to be a critical determinant in the correction of pulmonary hypoplasia. PMID- 1895447 TI - Challenges and commitments. PMID- 1895448 TI - Transplantation of kidneys from pediatric cadaver donors to adult recipients. AB - Pediatric donors (less than 12 years old) are a potentially important source of kidneys for adult recipients. Previous reports of decreased graft survival and increased complication rates have made surgeons wary of using such kidneys. In 64 kidneys from younger donors transplanted to adult recipients the delayed graft function rate (41 versus 42%), and 2 and 3-year graft survival rates (67 versus 72% and 61 versus 65%, respectively) were similar to those seen with kidneys from adult donors. Kidneys from donors 24 months old or less experienced an 80% rate of graft loss at 1 year. When these kidneys are excluded the 1-year graft survival rate was similar to kidneys from older and younger donors (70 versus 77%). Mean serum creatinine at 1 year was similar in both groups (155 +/- 21 versus 151 +/- 10). Pediatric kidneys except those obtained from donors 2 years old or less are suitable for adult recipients. However, kidneys from very young donors may be more appropriate to pediatric recipients. PMID- 1895449 TI - Adjunct controlled inversion therapy following extracorporeal shock wave lithotripsy for lower pole caliceal stones. AB - The lower calix is responsible for a significant number of kidneys with residual stone fragments after extracorporeal shock wave lithotripsy (ESWL*). To compare the effectiveness of controlled inversion therapy as an adjunctive method to the elimination of calculous fragments, 42 patients who had undergone treatment for lower caliceal stones with a Siemens Lithostar lithotriptor were reviewed. Of the patients 25 had no adjunctive therapy and 17 underwent controlled inversion therapy. The success rate, effectiveness quotient and complication rate were analyzed. Followup consisted of ultrasound and a nephrotomogram 1 day and 1 to 3 months postoperatively. Complete removal of all stone fragments was achieved in 84% of the patients without an adjunctive maneuver and in 64.7% of those treated with controlled inversion therapy. The effectiveness quotient was 72.4% and 35.5%, respectively. The group treated without adjunctive therapy had fewer retreatment sessions and a lower complication rate. There were no complications related to the controlled inversion therapy and patient acceptance was generally enthusiastic. We conclude that controlled inversion therapy did not improve the results of ESWL for lower pole caliceal calculi. PMID- 1895450 TI - Prediction of septicemia following endourological manipulation for stones in the upper urinary tract. AB - We investigated 117 patients undergoing percutaneous nephrolithotomy, percutaneous nephrostomy, ureterorenoscopy, the push-back or push-bang procedure for ureteral stones, Double-J* ureteral stenting plus extracorporeal shock wave lithotripsy (ESWL), ESWL alone or cystoscopy. Blood samples obtained before, during and 1 hour after the procedure were cultured and assayed for endotoxin and tumor necrosis factor. Also, culture was done of the urine preoperatively and postoperatively, and the stones when they could be retrieved. There was a temporal relationship among bacteremia, endotoxemia and elevation of tumor necrosis factor. An unexpected finding was peroperative endotoxemia in a significant number of patients with stones. Risk factors noted for postoperative bacteremia, endotoxemia and/or elevation of tumor necrosis factor included preoperative endotoxin level, type of procedure, presence of preoperative bacteriuria and pyuria. With respect to the procedure the risk was greatest after the push-back method and least after cystoscopy (push-back method greater than percutaneous nephrolithotomy/percutaneous nephrostomy greater than Double-J stenting plus ESWL greater than ureterorenoscopy greater than ESWL greater than cystoscopy). If the risk factors are measured preoperatively it may be possible to identify the risk of postoperative bacteremia/endotoxemia and, therefore, septic shock postoperatively. Our patients appear to be a good clinical model to investigate the problems related to septicemia. PMID- 1895451 TI - The cold-knife technique for endourological management of stenoses in the upper urinary tract. AB - Between 1985 and October 1989 we managed 13 patients with primary and 43 with secondary obstruction of the upper urinary tract with the endourological cold knife technique. We treated 26 patients with stenosis of the ureteropelvic junction, 9 with infundibular stenosis, 12 with ureteral obstruction after inflammation or radiation therapy, 7 with stricture of the ureter in kidney transplants and 2 with stenosis of the ureter after ureterosigmoidostomy. Endourological management was successful in 42 of 56 cases with a decrease or total elimination of obstruction. Stenosis recurred in 9 patients. Our results indicate that the cold-knife technique should be attempted as the initial approach in all cases of primary or secondary obstruction of the upper urinary tract. PMID- 1895452 TI - Vesicoureteral reflux in patients with double pigtail stents. AB - A prospective study of 30 renal units in 27 patients with double pigtail ureteral stents seen at our hospital was done. The aim of the study was to confirm or rule out the occurrence of vesicoureteral reflux radiologically, and to define its degree in stented patients. During the filling phase of the cystourethrogram, reflux occurred in 19 of the 30 renal units (63%). Of those 19 renal units the reflux was grade 1/4 in 15 (79%), while in 4 (21%) it was of higher grades (2 to 3/4). During the voiding phase of the cystourethrogram reflux was observed in 24 of 30 renal units (80%). Of those 24 renal units reflux was of high grade (2 to 4/4) in 20 (83%), while it was low grade (1/4) in 4 (17%). In the presence of a double pigtail stent the ureteral peristaltic waves were sluggish and averaged 1 to 2 waves per minute in the 15 patients observed fluoroscopically for 1 minute after voiding. We conclude that in the majority of patients with double pigtail ureteral stents vesicoureteral reflux occurs at a low grade during vesical filling and at a high grade during voiding. Also, the stents adversely affect the ureteral peristaltic activities. PMID- 1895453 TI - Bladder substitutes controlled by the anal sphincter: a comparison of the different absorption potentials. AB - A comparative study of the absorption potentials of the simple rectal bladder (10 patients), modified rectal bladder (20) and ureterosigmoidostomy (10) was done with intrarectal instillation of 22sodium. Results indicate that absorption is significantly greater among patients with ureterosigmoidostomy. The emptying patterns of ureterosigmoidostomy and the modified rectal bladder were also studied by ascending scintigraphy with 99mtechnetium. Evidence was provided that in cases with ureterosigmoidostomy the isotope is distributed throughout the entire colon. These studies proved the role of the colorectal valve in preventing reflux of urine from the rectum to the proximal colon. Consequently, the surface area of colonic mucosa exposed to urine is decreased and the rate of reabsorption is limited. PMID- 1895454 TI - Urethral controlled bladder substitution: a comparison between Parks S pouch and hemi-Kock pouch. AB - To study the effect of the configuration of ileal reservoirs on the urodynamic features, 12 S bladders and 12 Kock pouches were compared. Volume capacity and pressure characteristics were studied 6 months postoperatively. The mean capacity of the reservoirs was 500 +/- 83 ml. for the S bladder and 536 +/- 56 ml. for the Kock pouch. The amplitudes of phasic contractions at 50%, 80% and 100% capacity were similar in both groups. However, the frequency of these contractions was higher in the S bladder. The intraluminal pressure at full capacity was 31 +/- 15 cm. water for the S bladder and 39 +/- 20 cm. water for the Kock pouch. The similar urodynamic features of the S and Kock pouches indicate their ultimate expansion into reservoirs of close physical characteristics and urodynamic behavior. PMID- 1895455 TI - The effect of intravesical bacillus Calmette-Guerin therapy on the upper urinary tract. AB - A total of 66 patients with low grade, low stage transitional cell carcinoma of the bladder who were treated with intravesical bacillus Calmette-Guerin (BCG) underwent cystourethrography to detect vesicoureteral reflux. BCG was instilled weekly for 6 weeks and monthly thereafter for up to 24 months. Whenever vesicoureteral reflux was found or morphological abnormalities were detected on excretory urography (IVP) an isotope renal scan was performed to evaluate the relative renal function. Vesicoureteral reflux was found in 13 patients (19.7%): 10 had grades 1 and 2A, and 3 had grade 2B reflux. The number of BCG instillations ranged from 8 to 22. IVPs were normal in 11 patients. In 2 patients mild unilateral dilatation was present before BCG instillations, and this remained unchanged during and after therapy. None of the 13 patients with vesicoureteral reflux had IVP features suggestive of urinary tuberculosis. In 11 patients the refluxing renal systems had normal relative renal function (50 to 55%). Two patients had a decrease to 40% of the relative renal function with normal IVPs, suggesting a nonBCG related cause. We conclude that BCG therapy is safe in patients with minimal reflux. PMID- 1895456 TI - Repair of severe anterior vaginal wall prolapse (grade IV cystourethrocele). AB - The classical approach for the repair of severe anterior vaginal wall prolapse is the use of transvaginal colporrhaphy or, more recently, an abdominal paravaginal repair. Severe cystoceles develop from weaknesses of the levator sling and pubocervical fasciae resulting in 2 main anatomical changes: a central defect between the pubocervical fasciae, and a sliding herniation of the bladder and urethra (paravaginal defect). We developed a new transvaginal technique for the repair of large cystoceles (grade IV) extending outside of the introitus at rest, which includes repair of the central defect by anterior colporrhaphy, and repair of the paravaginal herniation of the bladder base and bladder neck by a needle suspension of these structures. We report our experience within a 5-year period in the treatment of 51 cases of severe bladder prolapse (grade IV cystoceles), 46 of which required this combined procedure regardless of preoperative stress urinary incontinence status. Five patients underwent anterior colporrhaphy as the only procedure, since they were continent and demonstrated a well supported bladder neck from a previous suspension operation. Other vaginal abnormalities should be repaired simultaneously to provide adequate pelvic floor support. PMID- 1895457 TI - Spongiosography: a valuable adjunct to the diagnosis of urethral strictures. AB - To obtain better information on fibrotic tissue damage in urethral strictures we performed spongiosography, that is opacification of the spongy body by injection of contrast medium, in 32 patients in whom the diagnosis had already been established by uroflowmetry, urethrography and urethroscopy. Another 18 patients with erectile dysfunction served as the control group. The investigation was well tolerated by all patients and no side effects or complications were encountered. Attenuation or even interruption of the contrast medium within the corpus spongiosum on spongiosography clearly revealed the fibrosis in urethral strictures. The extent of scarring was completely independent of the clinical symptoms and urethrographic findings. Accordingly, our decision on the appropriate surgical treatment was based mainly on the results of spongiosography. If used as an additional routine investigation in cases of urethral stricture spongiosography may help to decrease the recurrence rate in the future. PMID- 1895458 TI - Treatment of posterior urethral strictures with a titanium urethral stent. AB - A total of 5 patients with recurrent posterior urethral strictures underwent endoscopic placement of an expandable endourethral stent made of titanium. Patient age ranged from 17 to 66 years (mean age 42.6 years). Followup ranged from 13 to 20 months (mean 14.1 months). Of the patients 4 presently have unobstructed voiding with no incontinence. To date no side effects have been directly related to the stents and no incrustations or calculi have formed. Our preliminary study supports the use of titanium urethral stents as an alternative form of treatment for selected urethral strictures. PMID- 1895459 TI - New rules imperil care for poor. PMID- 1895460 TI - Washington University School of Medicine looks toward another 'century of excellence'. PMID- 1895461 TI - Ventricle devices, artificial hearts in near future? PMID- 1895462 TI - From the Centers for Disease Control. Attempted suicide among high school students--United States, 1990. PMID- 1895463 TI - From the Centers for Disease Control. Infant mortality--United States, 1988. PMID- 1895464 TI - From the Centers for Disease Control. Child passenger restraint use and motor vehicle-related fatalities among children--United States, 1982-1990. PMID- 1895465 TI - The risk of transmission of HIV from health care professional to patient. PMID- 1895466 TI - The camel shed test. PMID- 1895467 TI - The crypto post-op pizza. PMID- 1895468 TI - Insulin-like growth factor and apolipoprotein B. PMID- 1895469 TI - Cat-scratch disease and bacillary angiomatosis. PMID- 1895470 TI - The Washington University-Barnes Hospital experience with lung transplantation. Washington University Lung Transplantation Group. AB - OBJECTIVE: --To review our experience with lung transplantation, emphasizing recipient selection, choice of procedure, functional results, and outcome. DESIGN: --Retrospective review of patients who received lung transplants at Barnes Hospital, St Louis, Mo, between July 1, 1988, and January 31, 1991. SETTING: --Washington University School of Medicine, St Louis, Mo, and Barnes Hospital, a medical school and its affiliated referral hospital, respectively. PATIENTS: --Sixty-nine lung transplant procedures were performed in 66 recipients. Patients with clinically and physiologically severe lung disease were selected according to predetermined guidelines. Underlying diseases in the recipients included chronic obstructive pulmonary disease, alpha 1-antitrypsin deficiency emphysema, cystic fibrosis, pulmonary fibrosis, primary pulmonary hypertension, Eisenmenger's syndrome associated with an atrial septal defect, bronchiectasis, eosinophilic granuloma, and lymphangiomyomatosis. INTERVENTION: - Double-lung, bilateral sequential, and single-lung transplantations were performed. Eight patients underwent en bloc double-lung transplantations or a modification of this procedure with separate bronchial anastomoses. Thereafter, the bilateral sequential approach to replacement of both lungs was performed in 26 patients. Thirty-two patients underwent single-lung transplantations. MAIN OUTCOME MEASURES: --Pulmonary function tests, arterial blood gas levels, pulmonary artery pressure, pulmonary vascular resistance, and actuarial survival. RESULTS: --Actuarial survival at 1 year for the 66 lung transplant recipients was 79%. Actuarial survival at 1 year was 82% for the bilateral lung transplant recipients and was 90% for the single-lung transplant recipients. In patients with either restrictive or obstructive lung disease, pulmonary function tests and arterial blood gas levels improved markedly after lung transplantation. In patients with primary pulmonary hypertension or Eisenmenger's syndrome, the pulmonary artery pressure decreased and the cardiac index increased into the normal range after single-lung transplantation. CONCLUSIONS: --In carefully selected patients with end-stage lung disease, single-lung and bilateral lung transplantations can significantly improve functional capacity, with promising early actuarial survival statistics after 1 year. PMID- 1895471 TI - Patient-controlled analgesia. Does a concurrent opioid infusion improve pain management after surgery? AB - OBJECTIVE: --To assess the influence of a continuous (basal) morphine infusion as part of a patient-controlled analgesia (PCA) system on the postoperative analgesic requirement and on recovery parameters following abdominal hysterectomy. DESIGN: --Single-center, randomized, controlled protocol. SETTING: -University medical center. PARTICIPANTS: --A total of 230 adult women were randomly assigned to receive no morphine infusion (control group) or a continuous 0.5-, 1.0-, or 2.0-mg/h morphine infusion. Each patient was able to self administer supplemental intravenous bolus doses of morphine (1 to 2 mg) using a PCA infuser. MAIN OUTCOME MEASURES: --Use of the PCA device, opioid-related side effects, recovery times, and the patients' assessment of pain and sedation on linear visual analog scales were recorded during the 72-hour study period. Follow up questionnaires were completed by the patients and their health care professionals to assess the overall adequacy of PCA therapy. RESULTS: --Patients who received the 2-mg/h morphine infusions received significantly more opioid medication 9 to 72 hours after their operation than those who received no infusion (control group). The presence of a continuous morphine infusion of 0.5 to 2 mg/h did not significantly decrease the number of patient demands or supplemental bolus doses administered compared with the control group. Overall, 168 (84%) of the 199 patients who completed the 72-hour study were able to achieve adequate analgesia without requiring changes in the PCA regimen or experiencing major side effects. Recovery times and outcome variables were similar in all four groups. CONCLUSION: --The routine use of a continuous opioid infusion in combination with a standard PCA regimen does not improve pain management compared with PCA alone after abdominal hysterectomy. PMID- 1895472 TI - Tissue transformation into bone in vivo. A potential practical application. AB - The transformation of mesenchymal tissue, such as muscle, into cartilage and bone can be induced by the recently purified osteoinductive factor, osteogenin, and by its parent substratum, demineralized bone matrix. We investigated the possibility of transforming readily available muscle flaps into vascularized bone grafts of various shapes that could be used as skeletal replacement parts. In a rat experimental model, thigh adductor muscle island flaps were placed inside bivalved silicone rubber molds. Prior to closure of the mold, 18 flaps were injected with osteogenin and coated with demineralized bone matrix. Five flaps served as controls and were injected with the vehicle only, and not coated with demineralized bone matrix. The molds were implanted subcutaneously in the rats' flanks and reopened 10 days later. The control flaps consisted of intact muscle without any evidence of tissue transformation, whereas the flaps treated with osteogenin and demineralized bone matrix were entirely transformed into cancellous bone that matched the exact shape of the mold. Using tissue transformation, we were able to generate in vivo, autogenous, well-perfused bones in the shapes of femoral heads and mandibles. PMID- 1895473 TI - Demonstration of specific binding of cocaine to human spermatozoa. AB - Exposure of males to cocaine has been linked to abnormal development of their offspring. To investigate the possible role of sperm, this study examined the interaction of cocaine with human spermatozoa. Washed sperm were incubated with tritiated cocaine (6.7 nmol/L) with or without unlabeled cocaine (670 mumol/L), and the samples were filtered and the remaining radioactivity quantitated. The specific binding was optimal at 20 minutes and 23 degrees C. Competition studies with tritiated cocaine (3.4 to 66.6 nmol/L) indicated the presence of approximately 3.6 x 10(3) binding sites per cell, with a high affinity receptor dissociation constant (Kd = 12.6 nmol/L). Cocaine concentrations as high as 670 mumol/L had no detectable effect on either the motility or viability of the cells. These results support the hypothesis that the sperm may act as a vector to transport cocaine into an ovum. This novel mechanism could be involved in the abnormal development of offspring of cocaine-exposed males. PMID- 1895474 TI - Immunoglobulin deficiency and idiotype expression in children developing Haemophilus influenzae type b disease after vaccination with conjugate vaccine. The Collaborative Study Group. AB - OBJECTIVE: --Haemophilus influenzae type b (Hib) conjugate vaccines are effective in preventing Haemophilus disease in most children. The reasons why the vaccination fails in some children are unknown. This study investigated host factors in children who developed the disease despite conjugate vaccination. DESIGN, PATIENTS, OUTCOME MEASURES:--A convenience sample of 23 patients in whom Hib disease developed 14 days or more after conjugate vaccination was investigated for the presence of subnormal serum immunoglobulin concentrations and anticapsular antibody responses to Hib disease. We also investigated expression of the Hib idiotype 1 (Hibld-1), a serological marker of a VKII chain that comprises a major portion of the normal variable region repertoire of the antibody response to Hib polysaccharide. The results were compared with those of 149 patients in whom the unconjugated Hib polysaccharide vaccine failed and of 90 unvaccinated patients who developed the disease. RESULTS: --Compared with children in whom the unconjugated polysaccharide vaccination failed, the relative risk of a subnormal serum concentration of IgM, IgA, IgG, and/or IgG2 in the children in whom the conjugate vaccination failed was 4.9 (95% confidence interval [CI], 1.8 to 14; P less than .003) and of IgG2 was 22 (95% CI, 3.5 to 146; P less than .001). With the exception of the children with subnormal serum immunoglobulin concentrations, most of the children with conjugate vaccination failure showed normal or high anticapsular antibody responses to the disease, whereas the children with polysaccharide vaccination failure showed impaired responses. The Hibld-1 was expressed by the majority of the children in both vaccination failure groups and of the unvaccinated patients. CONCLUSIONS: --In most patients, vaccination failure is not attributable to lack of expression of the variable region gene encoding Hibld-1. However, children in whom conjugate vaccination has failed frequently have subnormal serum immunoglobulin concentrations and should be evaluated for immunodeficiency. PMID- 1895475 TI - The human genome project. Prospects and implications for clinical medicine. AB - The recently initiated human genome project is a large international effort to elucidate the genetic architecture of the genomes of man and several model organisms. The initial phases of this endeavor involve the establishment of rough blueprints (maps) of the genetic landscape of these genomes, with the long-term goal of determining their precise nucleotide sequences and identifying the genes. The knowledge gained by these studies will provide a vital tool for the study of many biologic processes and will have a profound impact on clinical medicine. PMID- 1895476 TI - Successful surgical treatment of atrial fibrillation. Review and clinical update. AB - Atrial fibrillation is the most common of all sustained cardiac arrhythmias, yet it has no effective medical or surgical therapy. During the past decade, multipoint computerized electrophysiological mapping systems were used to map both experimental and human atrial fibrillation. On the basis of these studies, a new surgical procedure was developed for atrial fibrillation. Between September 25, 1987, and July 1, 1991, this procedure was applied in 22 patients with paroxysmal atrial flutter (n = 2), paroxysmal atrial fibrillation (n = 11), or chronic atrial fibrillation (n = 9) of 2 to 21 years' duration. All patients were refractory to all antiarrhythmic medications, and each patient failed to receive the desired therapeutic benefits of an average of five drugs administered preoperatively. There were no operative deaths and all perioperative morbidity resolved. All 22 patients have been successfully treated for atrial fibrillation with surgery alone. Three patients developed one late isolated episode of atrial flutter at 5, 6, and 15 months postoperatively, and each of these patient's symptoms is now controlled by a single antiarrhythmic drug. Preservation of atrial transport function has been documented in all patients postoperatively, and all have experienced marked clinical improvement. PMID- 1895477 TI - Washington University and the creation of the teaching hospital. PMID- 1895478 TI - Serodiagnosis of invasive amebiasis using a recombinant Entamoeba histolytica protein. AB - One hundred eight serum samples from 106 patients were examined by Western blot analysis for the presence of antibodies to a recombinant fusion protein containing the sequence of the newly described serine-rich Entamoeba histolytica protein (SREHP). Among patients with invasive amebiasis from Durban, Republic of South Africa; San Diego, Calif; Mexico City, Mexico; and St Louis, Mo, 53 (82%) of 65 had antibodies to SREHP. In contrast, only one patient (2%) of 43 without acute invasive amebiasis had antibodies to SREHP. The predictive value of a positive test for anti-SREHP antibodies in the detection of acute invasive amebiasis was most marked when analyzed in the patients from Durban, where 11 (92%) of 12 patients who were seropositive for SREHP had acute invasive amebiasis vs 17 (65%) of 26 patients who had a positive serologic diagnosis as determined by agar gel diffusion. The use of a serologic test based on the recombinant SREHP fusion protein may be a useful adjunct to the diagnosis of acute invasive amebiasis in endemic regions. PMID- 1895479 TI - Ultrasonography of acute abdominal pain in children. AB - OBJECTIVE: --To determine the ability of ultrasonography to detect appendicitis and to identify other conditions responsible for symptoms in children with acute abdominal pain. DESIGN: --Cohort study. The accuracy of ultrasonographic results was assessed in relation to final diagnoses established by surgery or by composite clinical data and follow-up. SETTING: --Metropolitan, pediatric hospital; ambulatory and hospitalized patients. PATIENTS: --Consecutive sample of 178 pediatric patients who were referred for ultrasonography because of suspected acute appendicitis, but in whom the diagnosis could not be definitively established by clinical criteria. RESULTS: --Appendicitis was proven at surgery in 38 patients. Ultrasonography demonstrated the findings of appendicitis (noncompressible appendix with or without concomitant periappendiceal fluid collection or appendicolith) in 31 (82%) of these patients. Among the 140 children without appendicitis, other specific diagnoses were established by clinical, laboratory, and radiologic findings in 58 patients (including gynecologic diseases in 25, gastrointestinal tract abnormalities in 17, renal diseases in six, and extra-abdominal disease in 10). Ultrasonography aided in the diagnosis of other conditions in 34 (59%) of these 58 patients. No definitive clinical diagnosis was established in the remaining 82 patients. There were no false-positive results of ultrasonography. CONCLUSION: --Approximately half of children referred for suspected appendicitis will have a final diagnosis of abdominal pain of unknown origin. In the remainder, ultrasonography is useful, both to establish the diagnosis of appendicitis and to aid in diagnosing other causes of acute abdominal pain. PMID- 1895480 TI - Frontiers in surgery. A perspective. PMID- 1895481 TI - Washington University School of Medicine. A century of success. PMID- 1895483 TI - Tuberculosis screening in a nursing home: indications for preventive therapy. PMID- 1895482 TI - The risk of sidestream smoke to pipe smokers. PMID- 1895484 TI - Scar cancer of the lung. PMID- 1895485 TI - Hyperprolactinemia and depression. PMID- 1895486 TI - A new approach to the diagnosis of central venous catheter sepsis. AB - One hundred forty-four cancer patients harboring a central venous catheter (CVC) were prospectively investigated to assess the relationship between hub culture, clinical assessment of sepsis before removal, and CVC sepsis. In 22 patients, the CVC was removed because of clinical assessment of catheter sepsis expressed by the staff prior to the removal. For each CVC removal, peripheral blood (qualitative method), hub, and CVC tip (quantitative method) cultures were performed. Clinical sepsis (disappearance of fever after CVC removal) was observed in 13 patients, microbiologic "sepsis" (identification of the same microorganisms on the CVC tip and in the peripheral blood) in seven patients, and clinical and/or microbiologic sepsis in 16 patients. Staphylococcus epidermidis was the microorganism most frequently identified. Hub culture was negative in 48% and positive for a low number and a high number of colonies in 35% and 17%, respectively. The predictive value of hub culture was 96% when testing negative and 8% and 37% (p = 3 x 10(-3)) when testing positive for a low and a high number of colonies, respectively. Predictive values of clinical assessment were 55% if positive and 97% if negative. Combining hub cultures and clinical assessment, the risk of sepsis varied from 2% with both evaluations negative to 89% in the case of positive clinical assessment associated with positive high-count hub. Inasmuch as the CVCs used have a disposable hub, it is possible to have an accurate diagnosis of CVC sepsis without removing the CVC. PMID- 1895487 TI - Assessment of energy expenditure by indirect calorimetry in healthy subjects and patients with liver cirrhosis. AB - The reliability of resting energy expenditure (REE) measurements by indirect calorimetry with a ventilated hood was investigated in 50 healthy controls and 10 patients with liver cirrhosis. In each subject basal energy expenditure (BEE) was determined once and REE three times (morning REE1, noon REE2, afternoon REE3). In controls and patients the first 5-minute BEE and first 5-minute REE (controls also second 5-minute REE) were higher than in the remainder of the 30-minute recording. Only the last 20 minutes of recordings were used to calculate BEE (1645 +/- 315, mean +/- SD, in kilocalories per day), REE1 (1880 +/- 365), REE2 (1782 +/- 384), and REE3 (1775 +/- 316) in controls, and in cirrhotics: BEE (1530 +/- 235), REE1 (1714 +/- 267), REE2 (1715 +/- 238), and REE3 (1779 +/- 275). REE was higher than BEE in controls and cirrhotics (p less than 0.05). The REE variation coefficient was 5 +/- 3% in controls and 5 +/- 2% in cirrhotics. No systematic difference between REE1, REE2, and REE3 was found. Energy expenditure predicted by the Harris-Benedict equation differed up to 21% from measured BEE in individual controls; group mean BEE, however, was correctly predicted. In cirrhotics differences between measured and predicted BEE up to 26% occurred, while measured BEE was higher than predicted BEE (p = 0.06). It is concluded that REE can be reliably assessed by indirect calorimetry with a ventilated hood system in controls and patients at any time of the day, when values obtained in the first 10 minutes are deleted.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1895488 TI - Evaluation of serum visceral protein levels as indicators of nitrogen balance in thermally injured patients. AB - The use of serum visceral protein concentrations as predictors of nitrogen balance was assessed during the first 4 weeks following thermal injury. The correlation between nitrogen balance and serum albumin was not significant. Statistically significant correlations were found between nitrogen balance and serum prealbumin, retinol-binding protein, and transferrin. However, even the best correlation (retinol-binding protein, r = 0.388) was too weak to permit prediction of nitrogen balance on the basis of the visceral protein concentration. The correlation between change in direction of nitrogen balance and change in direction of protein concentration over time showed all four visceral proteins to be poor predictors of change in nitrogen balance. The efficiency was less than 50% for each visceral protein. Stepwise multiple regression analysis performed to determine which indices were most closely correlated with nitrogen balance showed that a calculation using readily available information (nitrogen intake, postburn day, percent total body surface burned, and age) provided better prediction of nitrogen balance (r = 0.765) than any of the visceral protein concentrations. In view of these findings, measurement of serum visceral protein concentrations to monitor adequacy of nutritional support seems an unwarranted expense in patients with thermal injury. PMID- 1895489 TI - The role of albumin in human physiology and pathophysiology, Part III: Albumin and disease states. AB - The serum albumin level is one of several clinical parameters of the status of general health. There is a marked correlation between low albumin levels and the incidence of morbidity and mortality in hospitalized patients. Therefore, it is not surprising to find that hypoalbuminemia is a common finding among hospitalized patients. This results from alterations in the catabolic or anabolic rates, losses of albumin, or redistribution between the various fluid compartments of the body. Somewhat less well defined than the role of albumin as a prognostic indicator is its role in compounding pathophysiology. Hypoalbuminemia is known to be associated with delayed wound healing. The hypoalbuminemic state interferes with the normal functioning of the gastrointestinal tract. Qualitative changes in the albumin molecule which occur in renal disease may damage the nephron. Low serum albumin levels may adversely affect the coagulation system. Further investigation into the role of albumin in pathophysiology is warranted. PMID- 1895490 TI - Use of albumin as a volume expander. AB - In some hospitals, albumin products account for 10% of the pharmaceutical budget. As much as 60% of these prescriptions are empiric, and from 40 to 70% of albumin that is administered is given for inappropriate reasons. Although the reasons for albumin administration vary, prevention or reversal of hypovolemia is part of the reason in the majority of cases. PMID- 1895491 TI - A case of intracerebral air embolism secondary to the insertion of a Hickman line. AB - Complications following the insertion of intravenous catheters are relatively uncommon. We report a potentially serious, hitherto unrecognized complication of Hickman line insertion, and discuss the condition. PMID- 1895493 TI - Surgical training: a personal view. PMID- 1895492 TI - Significantly decreased: clinically impaired? PMID- 1895494 TI - Fulminant hepatic failure with typhoid fever in childhood. AB - Although hepatic dysfunction has been described among adults with typhoid, there are few reports of significant hepatic functional impairment in children with typhoid. Of 355 children with culture proven typhoid seen at the Aga Khan University Hospital, hepatomegaly was noted in 118 (33%) and isolated right hypochondrial tenderness in 30 (8.5%). The liver function tests were normal in 78% and 47% of these children respectively and significant hepatic dysfunction was seen only in 26 (7.3%). However, children with typhoid and significant hepatic dysfunction had higher mortality (P less than 0.001) and two patients presented with a picture of fulminant hepatic failure with fatal outcome. PMID- 1895495 TI - Differentiation of cirrhotic Vs idiopathic portal hypertension using 99mTc-Sn colloid dynamic and static scintigraphy. AB - Thirty-seven cases of portal hypertension with endoscopically proven oesophageal varices underwent liver biopsy to determine the etiology of portal hypertension. Of the total, 19 had cirrhosis and 18 idiopathic portal hypertension (IPH). Later all these patients underwent Tc99mSn colloid, static and dynamic scintigraphy of the liver and spleen. Ratios of the area and of the integral and slope of the integral for liver and spleen were calculated to see if any of these ratios can differentiate cirrhotics from IPH. Significant difference (P less than 0.001) was noted in the ratio of the area (L/S) in both patients and controls, but the ratios of the integral and the slope of the integral were not only significantly different (P less than 0.001) in the patients and controls but also in the two groups of patients (cirrhosis and IPH). The sensitivity of this test when compared with the histology was 58% for both cirrhosis and IPH but when compared with clinical diagnosis it was 76% for cirrhosis and 62% for idiopathic group. Therefore by adding the above mentioned test in the routine study of liver scintigraphy in patients with portal hypertension, further differentiation of cirrhotic group can be done from the idiopathic group. PMID- 1895496 TI - Transhiatal oesophagectomy for carcinoma oesophagus. Early experience. AB - Over a period of eighteen months, (June, 89 to Dec, 90) 19 patients underwent Transhiatal Oesophagectomy for carcinoma. Thirteen were males and 6 females, age varying from 32 to 80 years with an average of 48.6 years. Dysphagia was present in all patients, the duration varied from 1.5 to 6 months, average 3.5 months. Pre-operative endoscopy and biopsy was done in all cases. Lesion was located in upper thoracic oesophagus in 6, middle 9 and lower 4. Histology revealed squamous cell carcinoma in 18 and adenocarcinoma in one. Transhiatal oesophagectomy without thoracotomy and cervical oesophagogastric anastomosis was carried out. The stomach was placed in the posterior mediastinum in 13 and retrosternal in 6 cases. Liver metastasis were present in 3, palpably enlarged nodes in 7 and the tumor was adherent to tissues in the mediastinum in 6 cases. Four patients died in hospital, 2 due to myocardial infarction, one due to massive haemetemesis, and the cause of death could not be established in one. Satisfactory relief of dysphagia was achieved in all cases. Oesophagectomy without thoracotomy is safe and better tolerated than the traditional trans-thoracic operations. The experience of one surgical unit is presented. PMID- 1895497 TI - Seroepidemiology of toxoplasma gondii infection in young school children in Islamabad. AB - Sera, from 270 school children (age 13 to 20 years) residing in suburbs of Islamabad, were investigated for the presence of toxoplasma gondii, IgG antibodies using the enzyme linked immunosorbent assay (ELISA). The overall prevalence was 17.4%. There was no significant difference between the two sexes. Since a positive test result for IgG antibodies at any level does not eliminate the possibility of a current infection, the toxoplasma IgG antibody positive children were further tested for the presence of toxoplasma IgM antibodies by the same technique. An acute infection was indicated in 12.7% (6/47) IgG positive children. This study shows that toxoplasmosis is prevalent in adolescence in Islamabad. The presence of cats and the degree of soil contact appeared compatible with hypothesis of transmission by oocysts. Poor sanitary habits and conditions and water shortage in schools may cause parasitic infection through contact between the children. An improvement in general hygienic conditions is important in reducing the rate of transmission by oocysts. Further studies are needed to assess the possible age of exposure to this parasite in the paediatric group. PMID- 1895498 TI - Prevalence of epilepsy in children (a population survey report). AB - A population based epidemiologic study carried out in a lower socioeconomic suburb of Karachi, identified 23 children with epilepsy among 994 children (3-9 year old) surveyed for childhood disabilities. Nineteen had major epilepsy, 2 petitmal and one each had focal motor and myoclonic attacks. The high frequency of epilepsy may be due to consanguinity, central nervous system, infections and birth and accidental trauma. PMID- 1895499 TI - Heterogeneity of methotrexate binding in human colon tumor cells. AB - [3H]-methotrexate binding at pH 5.0 and pH 7.2 by the cytosol of tumor tissues and the surrounding normal areas of the gastrointestinal tract of patients suffering from colon or gastric cancer has been used to identify in these cells the presence of a binder of methotrexate having low-affinity for this drug in addition to the enzyme dihydrofolate reductase. Scatchard analysis of the [3H] methotrexate binding data by a colon tumor sample also reveals that there are two binders of this drug present in the cytosol of these cells. The association constant (Kass) for one binder of methotrexate is = 5.6 x 10(7) M-1 while the Kass for the second binder is = 1.0 x 10(6) M-1. The two binders do not differ very much in their apparent molecular weight. Upon isoelectric focusing, the tumor cell cytosol resolves into 4 major isoproteins each having the ability not only to bind [3H]-methotrexate but also reduce [3H]-pteroylglutamic acid to [3H] tetrahydropteroylglutamic acid. This suggests that the two binders of methotrexate may be the two forms of dihydrofolate reductase having different affinities for this anticancer drug. PMID- 1895500 TI - Holt-Oram syndrome. PMID- 1895501 TI - Successful eradication of Flavobacterium meningosepticum neonatal meningitis with ceftizoxime. PMID- 1895502 TI - Epidemiologic patterns and control strategies in typhoid fever. PMID- 1895503 TI - S.I. units and conversion factors for old units for routine substrates in blood. PMID- 1895504 TI - Evaluation of right ventricular function using gated equilibrium blood pool radionuclide ventriculography in patients with congenital volume and pressure overload late after surgical repair. AB - The effects of congenital right ventricular pressure and volume overload were studied in 3 patients with pulmonary stenosis, 7 with atrial septal defect and 6 with atrial septal defect plus pulmonary stenosis late after successful surgical correction. Gated equilibrium blood pool radionuclide ventriculography was used to measure right ventricular function at rest and during exercise and to compare it with eight normal subjects. Right ventricular ejection fractions at rest and during exercise were measured to be 61 +/- 9% and 66 +/- 13%, respectively, in the group with pulmonary stenosis, 49 +/- 7% and 54 +/- 8% in the group with atrial septal defect, and 65 +/- 13% and 69 +/- 13% in the group with atrial septal defect plus pulmonary stenosis. The values in the groups with pulmonary stenosis and atrial septal defect plus pulmonary stenosis were significantly higher than the control subjects (45 +/- 5% and 51 +/- 5%, p less than 0.01). The peak filling rate at rest and during exercise was also significantly higher in the groups with pulmonary stenosis and atrial septal defect plus pulmonary stenosis than in controls (at rest, 2.72 +/- 0.72, 2.53 +/- 0.94 vs. 1.64 +/- 0.24 p less than 0.05; during exercise, 4.38 +/- 1.23, 4.13 +/- 1.18 vs. 2.52 +/- 0.62, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1895505 TI - Reproducibility of diurnal variation of heart rate. AB - Heart rate variation has been utilized as a parameter for validating autonomic nerve and sinus node function. However, few reports are available on the reproducibility of such data. In the present study, we studied the reproducibility of the diurnal variation of heart rate in 15 patients, and the effect of age differences on the variation in 30 normal men using a Holter ECG monitoring method. For investigating reproducibility, Holter ECG monitoring was performed twice, the two measurements being separated by a short interval. A moving average method applied on heart rate of every 3h exhibited essentially the same diurnal pattern of heart rate between two records in each patient. Excellent reproducibility of the pattern was also demonstrated by a lag correlation analysis. Variability of heart rate in normal men was independent of age. These results suggest that heart rate variation was essentially constant in each subject, at least within a short period. PMID- 1895506 TI - Prognostic significance of long ventricular pauses in athletes. AB - The long-term prognosis of athletes with long ventricular pauses has been unknown. In this study, thirty highly-trained cross-country skiers and 24 age matched controls underwent 24 h Holter monitoring to detect the duration of the longest ventricular pause (LVP), and we followed the athletes for more than 3 years to evaluate prognostic significance of prolonged LVP. The LVPs of the athletes averaged 2.2 +/- 0.6 sec (range 1.3-3.4), which were significantly longer than those, 1.6 +/- 0.3 sec, of the controls. In the athletes, 20 cases (66.7%) had LVPs more than 2 sec, and 5 (16.7%) showed LVPs longer than 3 sec. During 3 years follow-up, no athletes had symptoms of near syncope, syncope or death under continued heavy training. Our study suggested that athlete with prolonged ventricular pause, even of 3 sec or more, did not have a different clinical risk than those without long pauses. PMID- 1895507 TI - Disappearance of mitral valve regurgitation after successful percutaneous transluminal coronary angioplasty. AB - Percutaneous transluminal coronary angioplasty has been reported to improve several clinical parameters. Functional papillary muscle dysfunction, which is also known to induce mitral valve regurgitation, is reversible after revascularization. We described a patient, with a 95% stenosis of proximal right coronary artery, whose mitral valve regurgitation disappeared after successful percutaneous transluminal coronary angioplasty. PMID- 1895508 TI - A case of atrioventricular nodal reentrant tachycardia with 2:1 infra-His block and type 1 gap phenomenon. PMID- 1895509 TI - Natural histories of atrial septal defect with pulmonary hypertension, and ventricular septal defect with pulmonary hypertension. AB - A study of the natural history of 51 adult patients with atrial septal defect with pulmonary hypertension (ASD + PH) was performed. ASD + PH of less than 14 Um2 of pulmonary artery resistance (PVR) was considered an indication for surgery. The prognosis of surgically treated patients was favorable, but that of medically treated patients was poor. For patients with ventricular septal defect with pulmonary hypertension (VSD + PH), surgery was considered for pulmonary systemic vascular resistance ratio (Rp/Rs) less than 0.5, and for patients under than 10 years and, ideally, under 2 years of age. PMID- 1895510 TI - Infective endocarditis--analysis of 116 surgically and 26 medically treated patients. AB - We have reviewed 116 cases of bacterial endocarditis treated surgically and 26 cases treated medically since 1973. There were 123 patients with native valve endocarditis and 19 patients with prosthetic valve endocarditis. Overall, the left-sided valves were infected most frequently. There were 10 cases with right sided valves involved. Multiple valves were infected in 6 patients. There were 6 perioperative deaths in the surgical group. The most common cause of death was multi-organ failure associated with uncontrollable sepsis. The overall operative mortality for active endocarditis was 7.7% (4/55), and for healed endocarditis, 3.3% (2/61). For active native valve endocarditis, the mortality was 4.2% (2/48), for healed native valve endocarditis, 3.6% (2/55), for active prosthetic valve endocarditis, 28.6% (2/7), and for healed prosthetic valve endocarditis, 0%. There was no difference in the operative mortality between active native valve endocarditis and healed native valve endocarditis. The mortality of active prosthetic valve endocarditis was significantly higher than that of active native valve endocarditis (p less than 0.01). Of the 26 patients treated medically, 7 died during the initial hospitalization. The major factor related to mortality in the medically treated patients was persistent sepsis (four patients), and congestive heart failure (three patients). The overall mortality of the medical group for active valve endocarditis was 15% (3/20), and for active prosthetic valve endocarditis, 67% (4/6). We conclude that patients with infective endocarditis with significant valve lesions who are unresponsive to medical therapy should be considered for urgent surgery. PMID- 1895511 TI - Medical treatment or surgical intervention? A cooperative retrospective study on infective endocarditis--timing of operation. AB - Two hundred and five patients treated for infective endocarditis over the last 10 years were reviewed. There were 185 cases of native valve endocarditis (NVE) and 20 of prosthetic valve endocarditis (PVE). In the NVE group there were 175 clinically active patients and 10 non-active patients. The mortalities among 108 non-surgical and 57 surgical patients were 15.7% and 14.0%, respectively. Leading causes of deaths in the former were cardiac failure, embolism and cerebral hemorrhage. Patients with embolism showed significantly higher mortality. Culture negative endocarditis resulted in almost the same incidence of hospital death and urgent operation as staphylococcal endocarditis, and a higher incidence than streptococcal endocarditis. In 9 of 33 patients operated at our hospital, surgery was performed on an urgent basis and one NYHA class IV patient died. Indications for operation were intractable cardiac failure, uncontrollable infection and angina. In the PVE group, 3 of 4 patients operated in the active stage died of severe cardiac failure generated preoperatively. The only survivor was a patient operated early under stable hemodynamics. These results suggest that culture negative endocarditis should be observed as closely as staphylococcal endocarditis and early operation should be considered for patients with progressive cardiac failure, embolism and uncontrollable infection. PMID- 1895512 TI - Initial success rate and complications of elective PTCA in 5064 patients. AB - From October 1981 to May 1990, 7000 elective percutaneous transluminal coronary angioplasties (PTCA) were performed at the Kokura Memorial Hospital, of which 5064 were analyzed using our computer system. The primary success rate of PTCA was 85%, in 1 vessel disease 88%, in 2 vessel disease 85%, and in 3 vessel disease 79%. Complications of PTCA were as follows: myocardial infarction, 2.1%; emergency CABG, 0.5%; death, 0.6%. We analyzed predictive factors for in-hospital death or emergency CABG. Five significant factors are significantly related: cerebral vascular accident, chronic renal failure, jeopardized collateral, abrupt closure, and dilatation of the left anterior descending artery. PMID- 1895513 TI - Percutaneous transluminal coronary angioplasty and coronary artery bypass surgery -early and follow-up clinical results. AB - To evaluate the efficacies of percutaneous transluminal angioplasty (PTCA) and coronary artery bypass grafting (CABG) for angina pectoris, early and follow-up data were reviewed in 495 patients who had undergone these procedures from 1986 to 1988. In 173 patients with single vessel disease, there were no significant differences in initial success rate and early and late incidences of major complications or cardiac death between 152 patients with elective PTCA and 21 with urgent. When compared in 161 patients with multivessel disease, however, significant differences in success rate were found between 130 patients in the elective PTCA group and 31 in whom PTCA was urgent (81.6% vs. 64.5%, p less than 0.05). Significant differences were also found in early incidence of major complications (3.1% vs. 12.9%, p less than 0.01), early mortality (1.5% vs. 9.7%, p less than 0.01), and the late incidence of cardiac events (6.2% vs. 25.0%, p less than 0.01). These results show that freedom from cardiac death and overall cardiac events in the elective PTCA group as significantly better than that in the urgent group at 42 months of follow-up. Comparing early and follow-up results, on the other hand, there was no statistically significant difference between the elective and urgent CABG groups. Thus, there appear to be limitations on the urgent use of PTCA for refractory unstable angina caused by multivessel disease, and urgent CABG was recommended to high-risk patients of urgent PTCA. PMID- 1895514 TI - Medical vs surgical treatment of acute aortic dissection in an intensive care unit. AB - To determine which therapeutic procedure is most appropriate for which type of aortic dissection, we investigated 146 cases of acute aortic dissection. In the group with dissection of the ascending aorta, 58.6% of patients given medical therapy and 48.8% of patients given surgical therapy died. In the group with dissection of the descending aorta, 14.0% given medical therapy and 50.0% given surgical therapy died. High mortality in the medical group with type A dissection was caused by delayed operation. Better survival was achieved in treated than surgically treated patients with acute distal dissection. In patients with cardiac tamponade, aortic regurgitation, hemothorax/hemo-mediastinum, visceral ischemia and peripheral ischemia, mortalities following medical treatment were fairly high. Surgical treatment brought on improvement in mortality in these groups. However, in the cases complicated by renal dysfunction, the mortality in the surgical group was higher than that in the medical group. 42 patients (28.8%) had no evidence of any complication and only 6 (14.3%) died. In 20 cases (47.6%) of uncomplicated dissection, no blood flow was observed in the false lumen. In cases with open false lumen, the following abnormal findings were more conspicuous: thrombocytopenia, decreased level of fibrinogen, increased fibrin degradation product and soluble fibrin monomer complex. However, these changes seem to be minimal in cases with thrombosed false lumen. The measurement of coagulation factors may be one useful method to determine which therapeutic procedure is most suitable. PMID- 1895515 TI - Acute aortic dissection. A comparison between the results of medical and surgical treatments. AB - Over the last ten years 96 patients with aortic dissection were encountered in our Institute, of whom 51 had type A dissection, and 45 had type B dissection. In the patients with type A dissection the long-term survival rate was poor if they were not operated upon without delay, and the cause of death was usually rupture of the aneurysms. In the patients with acute type B dissection the surgical indication was limited and, generally speaking the long-term survival rate of the medically treated patients was more favorable. PMID- 1895516 TI - [Progress of cytological and histological diagnosis for pancreatic diseases]. PMID- 1895517 TI - [Analytic methods of pancreatic lipase for diagnosis of pancreatic diseases]. PMID- 1895518 TI - [Diagnosis of pancreatic diseases by serum enzymes]. PMID- 1895520 TI - [Diagnosis and therapy of cardiac arrhythmias in the elderly]. PMID- 1895521 TI - [Neuropathological aspects of normal and abnormal aging]. AB - Several senile changes in the central nervous system in cadavers were examined. The pattern of extension of Alzheimer's neurofibrillary tangles (NFT) and senile plaques (SP) in the olfactory bulbs of 100 specimens was examined during routine autopsy by immunohistochemical staining. NFT were first observed in the anterior olfactory nucleus after the age of 60, and incidence rose with increasing age. Senile plaques were found in the nucleus when there were many SP in the cerebral cortex. Of 25 non-demented amyotrophic lateral sclerosis patients, SP were found in the cerebral cortices of 10, and 9 of 10 were over 60 years old. NFT were observed in almost all patients over 60 years of age, but the incidence was low. Many ubiquitin-positive small-sized granules were observed in the second and third layer of the parahippocampal gyrus of aged patients, and the incidence rose with increasing age. On the other hand, few of these granules were in patients with Alzheimer's type dementia. Granulovacuolar degeneration was examined. Many centrally-located granules were positive for ubiquitin. Based on electron microscopic observation of these granules at several stages, the granules were thought to be a type of autophagosome. During the first stage of granulovacuolar degeneration, electron-dense materials appeared in the cytoplasm, following which they were surrounded by smooth endoplasmic reticulum. Analytical electron microscopy disclosed that the granules contained some aluminium. PMID- 1895519 TI - [Antihypertensive treatment in the elderly]. PMID- 1895522 TI - [Normal and abnormal aging of cardiovascular system]. AB - Studies of normal aging in the cardiovascular system in humans are affected by the study population. Besides intrinsic biological aging, extrinsic factors including overt or latent cardiovascular diseases as well as life style variables such as physical activity, diet, alcohol and smoking may influence the age related changes of cardiovascular function. We have recruited "normal" elderly subjects from community-dwelling volunteers by extensive health screening procedures including treadmill maximum exercise tests. Some of their cardiovascular functions, such as various cardiovascular regulatory functions, were altered compared to normal young subjects, while others such as resting hemodynamics were not. Interrelationships among various autonomic functions in the elderly were not recognized. Although general effects of life styles on circulatory regulatory functions were not clearly indicated, variables such as sodium intake or body mass index appeared to affect some of the sympathetic nervous functions. Furthermore, hypertension in the elderly had much less impact on cardiovascular functions than is generally expected, based on the results from young or middle-aged subjects. To identify factors which either modify (accelerate) or do not affect the aging of the cardiovascular functions is important not only to achieve a good aging process but also to establish therapeutic goals in elderly subjects. PMID- 1895523 TI - [Age-related changes in the kidney of patients with mild mesangial proliferative glomerulonephritis]. AB - In order to clarify age-related changes in kidneys, the renal function and histological changes were evaluated in 962 patients with mild mesangial proliferative glomerulonephritis (Mes PGN) whose ages ranged from 7 to 82 years. The glomerular filtration rate (GFR) (Ccr), renal plasma flow (RPF) (CPAH) and PSP excretion rate were significantly lower in nephritic patients than in normal subjects. Age-related decreases of GFR, RPF, PSP excretion rate and maximal urine specific gravity in Fishberg concentration test were found in both groups. Serum levels of creatinine, urea nitrogen and uric acid were significantly higher in nephritic patients than in the normal population. Age-related increases of those parameters were found in both groups. The incidence of sclerotic glomeruli was almost same as that of the normal population estimated by Kaplan et al. The incidence of arterio- and arteriolosclerosis was also higher than that of normal subjects estimated by Bell. Thus, arterio- and arteriolosclerosis seems to be more age-dependent than glomerulosclerosis in patients with mild Mes PGN. In conclusion, renal functions decrease and renal arteriolar lesions increase gradually in proportion to aging. Mes PGN, even mild, can accelerate the physiological age-related decrease of renal function. PMID- 1895524 TI - [Physiological and pathological aging in bone--contribution of risk factors to bone loss with aging]. AB - This study was performed to investigate the mechanism of the pathological ageing of bone, evaluating the effect of risk factors for osteoporosis on bone mineral density in elderly women (n = 108), ovariectomized (OVX; n = 86) and hysterectomized (HX; n = 75) middle-aged women. Possible risk factors such as family history, physique, reproductive function, calcium intake, physical activity and past history were studied by using questionnaires. Parameters of bone metabolism such as serum Ca, P, Al-p, parathyroid hormone (PTH), osteocalcin, vitamin D metabolites and urinary Ca/creatinine ratio were also measured. Spinal bone mineral densities (BMD) were determined by dual energy X ray absorptiometry (DPX, Lunar). By multiple regression analysis, body height, PTH and serum Ca in HX group, alcohol consumption, serum Al-p, Ca, PTH, 1,25(OH)2D and 25(OH)D in OVX group were independent significant predictors for lumbar BMD. On the other hand, serum levels of Al-p and urinary Ca/creatinine ratio were independent, significant, but weak predictors in the elderly group. Thus, in the elderly group, it was difficult to predict specific factors affecting BMD when compared with the HX and OVX groups. Moreover, the coefficient of determination was smaller in the elderly group (r2 = 0.156) than those of the HX group (r2 = 0.205) and OVX group (r2 = 0.251). In elderly women, the frequencies of persons who dislike milk and who have low body weight (less than mean - SD) in low BMD with fractures were higher than those in normal BMD without fracture.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1895525 TI - [Physiological and pathological aging and electrolyte metabolism]. AB - The extracellular and intracellular concentrations of electrolyte were maintained by various systems including kidney and endocrine system. Although concentrations of electrolyte in the extracellular fluid were maintained in normal ranges in healthy elderly subjects, the reserve ability for the maintenance of electrolyte balance decreases with physiological aging. Occurrence of abnormality in electrolyte concentrations in extracellular fluid is thought to be related to pathological aging. The frequency of subjects with abnormal circulating concentrations of electrolytes, as well as abnormal rates of severe such abnormalities increase with age. Clinical characterization and differentiation of physiological and pathological aging are not always easy. On the other hand, the kidney is the central organ for maintenance of electrolyte homeostasis. Decrease in renal ability to retain electrolytes sometimes affect the features of disorders such as hypertension and osteoporosis of elderly subjects. Intravenous infusion of physiological saline at a dose of 20 ml/kg over 2 hr evoked excessive excretion of sodium, calcium and inorganic phosphate in the urine in hypertensive elderly patients and in some patients with senile osteoporosis. These subjects showed decreased levels of plasma renin activity and increased serum levels of parathyroid hormone and 1,25-dihydroxyvitamin D. These features indicate that abnormal renal metabolization of electrolytes involving abnormality of endocrine system may be a cause of, and modulate the clinical features of, some disorders of elderly subjects. PMID- 1895526 TI - [Echocardiographic assessment of the etiology of aortic regurgitation in the elderly]. AB - We performed echocardiographic studies in 189 elderly subjects aged over 65. Aortic regurgitation (AR) was detected by real time 2-D Doppler system. 189 patients were classified into 5 groups based on the severity of AR (AR-: 81 pts, AR1+: 32 pts, AR2+: 44 pts, AR3+: 27 pts, AR4+: 5 pts). The diameter of the aortic root, the angle (theta) between the aortic wall and interventricular septum and echo intensity of aortic valve were measured by 2-D echocardiography. There was no relation between the severity of AR and angle theta. Diameters of aortic root were significantly increased in AR3+ cases as compared with AR- and AR2+. Systolic blood pressure was significantly increased in AR4+ cases as compared with AR-, AR1+, and AR2+. Diastolic blood pressure was also decreased in AR3+ cases as compared with AR-. Echo intensity of aortic valve was increased in patients with AR. It was thought that increased diameters of the aortic root in patients with severe AR were induced from the long-standing AR, and that increased systolic blood pressure and decreased diastolic blood pressure in severe AR were caused by hemodynamic changes due to AR. Therefore, we concluded that AR in the elderly was caused by degeneration and/or deformity of the aortic valve. PMID- 1895527 TI - [Cerebrovascular disease in the elderly--a clinicopathological study of 45 autopsied cases with cortical artery infarction]. AB - The medical records and autopsy data of patients over the age of 70 years at death with a diagnosis of cortical artery infarction (CAI) in the Yokufukai Geriatric Hospital were reviewed. Among 690 autopsied cases from 1981 to 1988, there were 45 cases (21 men and 24 women) with CAI available for this study. Fourteen cases (31.1%) suffered CAI while hospitalized for another disorder. Their ages at death ranged from 70 to 102 years with a mean of 82.4 years. From the results of this neurological and psychological analysis, the residuals of senile stroke were classified into six subtypes: 1) cerebrovascular dementia, 2) cerebrovascular Parkinsonism, 3) pseudobulbar palsy, 4) chronic stage of aphasia, 5) slowly-progressive decreased motivation or spontaneity without dementia, 6) the so-called bedridden state (prolonged vegetative or apallic state). Sixty-nine percent had anamnetic hypertension before the stroke. The ages at which they became bedridden ranged from 69 to 102 years with a mean of 81.8 years. Within one year after becoming bedridden, 83.3% of all patients died. The bedridden state in the elderly with residual CAI indicated a poor prognosis within one year after stroke. Causes of death included brain death in 22.3% of all patients, pneumonia in 20.0%, and digestive bleeding in 8.9%. PMID- 1895528 TI - [Presence of circulating suppressive factor for muscarinic acetylcholine receptor in senile dementia]. AB - Alzheimer's disease is one of the main causes of senile dementia. Although its pathogenesis is not clear, some evidence has revealed that the activity of acetylcholine receptor in the brains of these patients is decreased. In the present study, possible circulating factors, affecting the muscarinic acetylcholine receptor of the synaptic vesicle from the rat brain, were evaluated in the serum of 95 senile subjects (34 males and 61 females, mean +/- SD age of 77.5 +/- 8.6 years). The cognitive function of these subjects was assessed by their Mini-Mental State scores, and they subjects were divided into non-dementic subjects with a score of 21 or more, or subjects with dementia with a score of 20 or less. The latter were further divided into senile dementia with Alzheimer type (SDAT) and vascular type dementia (VS) using Hatchinski's ischemic score. The mean suppression rate by the serum from the SDAT patients on the binding of tritiated quinuclidinyl benzilate (3H-QNB), an antagonist for muscarinic acetylcholine receptor, to the rat synaptic membrane, was 18.1 +/- 7.2% of the control value, which was significantly greater than that of the non-dementic subjects, (4.7 +/- 3.8%). However, that in the VD group (8.4 +/- 6.8%), was not significantly different from the control value. Moreover the suppression rate of the serum on 3H-QNB binding showed significant positive correlated with score for the Mini-Mental State (r = 0.480, p less than 0.01) in the SDAT group. These data support the hypothesis that circulating suppression factors may participate in the pathogenesis of SDAT. PMID- 1895529 TI - [Pigmented neuron/non-pigmented neuron ratio of the substantia nigra in relation to ageing and pathological conditions]. AB - Based on 45 normal cases aged from 32 to 106 years of age, a morphometric study revealed that, despite decrease in the number of both pigmented neurons (PN) and the non-pigmented neurons (NN) with advancing age, the ratio (PN/NN) did not change (4.8). It is well-known that both the substantia nigra and the striatum send fibers to each other. McGee demonstrated that the ratio of the number of large neurons to that of small neurons was constant, irrespective of different ages, although number of both neurons decreased with ageing. It was therefore apparent that this phenomenon in the putamen was the same as in the substantia nigra. It could be considered that "balanced depopulation of different neurons" in the nucleus of the strio-nigral circuit contribute to support normal extrapyramidal functions. Additionally, the centenarian cases showed larger numbers of both PN and NN than younger case. It was likely that they could be classified as so-called "excellent" centenarians. On the other hand, idiopathic Parkinson's disease (15 cases) showed that while the same number of NN remained as in age-matched controls, PN showed marked depopulation. Olivopontocerebellar atrophy of the sporadic type (OPCA, 10 cases) and progressive supranuclear palsy (PSP, 5 cases) showed a decrease in number of both PN and NN. However, NN in PSP showed much more decrease than OPCA. NN sends fibers to the pontine tegmentum as well as the thalamus, and PSP shows marked atrophy of the brainstem tegmentum. In this connection, it was considered that marked decrease of NN in PSP could be related to tegmental atrophy. PMID- 1895530 TI - [Differences in ventricle dilation and clinical findings between the early- and late-onset subtypes of Alzheimer's dementia]. AB - The authors compared the characteristics of the early-onset subtype of Alzheimer's dementia (AD) with those of the late-onset subtype (SDAT) to determine whether Alzheimer's dementia (AD/SDAT) can be divided into two different diagnostic categories. In this study, AD refers to Alzheimer's in which the onset of disease occurred before 65 years of age; and SDAT refers to cases in which onset of illness occurred at age 65 or more. The studied parameters were distribution of age at disease onset, progression of speed of ventricular dilation, speed of deterioration of Hasegawa's rating scale for dementia (HRSD) score, and lesional pattern on the Japanese revised version of the GBS scale (GBSS-JR). The distribution of age at onset in 258 patients with AD/SDAT showed one peak. These patients included both outpatients and inpatients. A 30-month follow-up study to determine the degree of ventricular dilation was performed in 20 AD and 24 SDAT patients. For CT measurement, the width of the third and lateral ventricle (cella media index) was measured every 6 months after admission. Average ventricle width at admission was matched between the two groups. Twelve and 24 months after admission, the mean cella media index of patients with AD was significantly wider than that of patients with SDAT. In addition a deterioration speed of HRSD scores of 16 AD and 14 SDAT patients was compared every month for 5 months after admission. The average duration of illness and HRSD score at admission were matched in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1895531 TI - [Dry cough in the elderly patients treated with angiotensin converting enzyme inhibitor]. AB - Since dry cough has recently been recognized as a side effect of angiotensin converting enzyme (ACE) inhibitors employed in the treatment of hypertension or congestive heart failure, the incidence of dry cough in elderly patients receiving ACE inhibitors was investigated. There were 237 out-patients on either captopril, enalapril, or delapril, in August and November 1989. Questionnaires concerning dry cough and smoking were completed by 184 patients. Patients either less than 50 years of age, or with chronic pulmonary disease were excluded. The remaining 168 patients, 63 males, 105 females, with a mean age of 73 years were analyzed for the incidence of a dry cough in relation to age, sex, smoking, and type of drugs. The overall incidence of a dry cough was 21/168 (12.5%), 7/63 (11.1%) for males and 14/105 (13.3%) for females, and was less frequent with advancing age; in the 51-60 age group 4/11 (36.4%), in the 61-70 age group 5/39 (12.8%), in the 71-80 age group 9/75 (12.0%), in the 81-90 age group 3/40 (7.5%), in the 91- age group 0/3 (0%). Enalapril showed significantly higher incidence of dry cough than captopril (16/93, 17.2% vs 7/88, 8.0%, p less than 0.05). Delapril showed an incidence 4/11, 36.4%, however, 9 out of the 11 patients who were given delapril had had a history of a dry cough with captopril or enalapril, and in 4 out of these 9 patients the dry cough disappeared by replacement of captopril or enalapril by delapril.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1895532 TI - [An MRI and SPECT study of frozen gait without other manifestations of parkinsonism in the elderly]. AB - The authors have sometimes experienced cases of frozen gait without any other manifestations of parkinsonisms in the elderly, so we examined these cases using MR imaging and SPECT imaging. The group with frozen gait (4 cases, aged 78 to 82 years) which failed to respond to L-dopa therapy, had no limb-kinetic apraxia or frontal signs, but did exhibit "kinesie paradoxale". The clinical symptoms of case 4 were consistent with so-called "pure akinesia". CT findings in this group failed to elucidate the pathogenesis of frozen gait. MR imaging of all of the cases except for the case of pure akinesia (case 4) revealed a high signal intensity areas in subcortical lesions (especially the frontal area). Case 4 had only a few spotty high-signal intensity areas. We then compared 6 cases which have the same lesions (on MRI) as cases 1-3 without frozen gait in cases 1-3 using 123I-IMP SPECT. Relatively low accumulation of radionuclide in the frontal area was observed in these cases. Case 4 had a slightly low perfusion area in the frontal lobe. However in the patient treated with L-threo-DOPS, accumulation of radionuclide in the frontal area increased slightly after L-threo-DOPS therapy. It appears that one of the reasons for frozen gait in the elderly is incomplete infarct of the subcortical white matter with a low perfusion area in the frontal cortex. Furthermore, in some cases of frozen gait it is difficult to distinguish between cases with white matter disorders and cases of pure akinesia on the basis of clinical symptoms and CT alone. PMID- 1895533 TI - [Mitral flow responses to two-week salt loading in elderly hypertensive patients]. AB - The effects of a two-week high sodium diet on mitral flow pattern were assessed in 29 patients with essential hypertension (81.9 +/- 6.9 years). Transmitral flow was recorded during different rates of salt intake; 7 g/day for 8 weeks and 20 g/day for 2 weeks. With sodium loading, 25 patients whose mean blood pressure (MBP) increased by 10 percent or more were termed salt-sensitive (SS) group, and 4 patients whose MBP did not change or increased by less than 10 percent were termed non-salt-sensitive (NSS) group with mitral flow velocity integral, cardiac output (CO) and total peripheral resistance (TPR) were calculated. Thirteen of the SS patients were defined as "SST" in which an increase in TPR was greater than that in CO with sodium repletion. In the remaining 12 SS patients termed "SSc", the increase in CO was greater than that in TPR with salt loading. CO increased significantly in the SSc patients, but did not change in the SST or NSS group with sodium loading. TPR increased significantly in the SST and NSS subjects, and decreased significantly in the SSc patients. Peak velocity of transmitral flow in the rapid filling phase (R) decreased significantly in the SST and NSS patients, and increased significantly in the SSc group. On the other hand peak velocity of transmitral flow in the atrial contraction phase (A) increased significantly in the SST and SSc groups, but remained unchanged in the NSS patients. There was a significant increase in A/R in the SSt group and a significant decrease in A/R in the SSc patients with sodium loading. PMID- 1895534 TI - [Three elderly cases of renal cell carcinoma with pancreatic metastasis]. AB - Three elderly patients, (an 80-year-old female, 78-year-old female and 78-year old male) suffering from renal cell carcinoma with pancreatic metastasis were reported. In all cases, renal cell carcinoma had been diagnosed previously. Pancreatic tumors were revealed by computed tomography and ultrasonic study during subsequent admission in all cases. In the first case, laparotomy and histological examination proved that pancreatic tumor was metastatic from renal cell carcinoma. In the other cases, according to their clinical course and other laboratory data, we considered the pancreatic tumors to be metastatics from renal cell carcinoma though histological diagnosis was not obtained. PMID- 1895535 TI - [Dementia-like state induced by terodiline]. PMID- 1895536 TI - [Significance of urinary cadmium concentration as an indicator of cadmium exposure in a population exposed to cadmium in a general environment]. AB - Study was made on the significance of urinary cadmium concentration as an indicator of internal dose in a general environment polluted by cadmium. As an index of external dose, the mean rice cadmium concentration in each of 23 villages was employed. Morning urine samples were collected from 3,178 inhabitants of 23 cadmium-polluted villages of Kakehashi River basin in Ishikawa Prefecture and 294 inhabitants of two nonpolluted villages. Cadmium concentration in urine was determined. In addition, their residential history and intake of cadmium-polluted rice were obtained. All the subjects were 50 years of age or over. Participation rates were 91% for the polluted area and 94% for the nonpolluted area. Urinary cadmium concentrations were higher in the inhabitants of the cadmium-polluted area than in those of the nonpolluted area. Among the inhabitants in the cadmium-polluted area, urinary cadmium concentrations were higher in the subjects who had consumed cadmium polluted rice than in those who had not. The mean urinary cadmium concentrations in each village increased proportionally to increase in mean village rice cadmium concentration (intensity of exposure) when the inhabitants were classified according to period of residence at their present address. The mean urinary cadmium concentrations in each village were also significantly correlated with period of residence at the present address (duration of exposure) when the inhabitants were classified according to mean rice cadmium concentration of their village. It is concluded that urinary cadmium concentration mainly reflects the body burden of cadmium in a general environment polluted by cadmium. PMID- 1895538 TI - [Changes in hematological and blood chemical findings following saturation diving: analysis of total of 113 divers]. PMID- 1895537 TI - An evaluation of efficacy of cigarette smoking cessation in preventing low levels of serum high-density lipoprotein (HDL) cholesterol. AB - Correlation of serum high-density lipoprotein cholesterol (HDL-C) with cigarette smoking and alcohol consumption habit was investigated in 562 male office workers aged 31 to 60 yr. HDL-C concentrations were found to be positively associated with alcohol consumption in subjects with relative weight below 10%, but a positive association was not observed in obese subjects having relative weight of 10% or above. In contrast, HDL-C levels were significantly lower in smokers than in non-smokers regardless of obesity. The effectiveness of smoking cessation in preventing low levels of serum HDL-C was estimated by comparing prevalence rates of HDL-C levels lower than an arbitrarily determined HDL-C cutoff value in smokers with those in non-smokers. The estimation was made with unadjusted subjects and also with subjects adjusted for age, relative weight and alcohol consumption. The effectiveness was found to be considerably high in heavy smokers having lower HDL-C levels (less than or equal to 35 mg/dl) with or without hypercholesterolemia (greater than or equal to 220 mg/dl) and further remarkably high in all smokers having hypertriglyceridemia (greater than or equal to 300 mg/dl) besides lower HDL-C levels. It is therefore expected that health education focused on stopping smoking can produce favorable alterations in HDL-C for preventing coronary heart disease, especially in heavy smokers having low serum HDL-C levels concomitant with hypercholesterolemia and/or hypertriglyceridemia. PMID- 1895539 TI - [Prevention of bone lesions in saturation divers: surveillance using bone scintigraphy]. PMID- 1895540 TI - [Evaluation of cold and heat tolerance of forestry workers by a questionnaire survey]. PMID- 1895541 TI - [A simple and reproducible method for determination of aluminum in tissue]. PMID- 1895542 TI - [Effective use of past health examination data--annual personal data reference at the place of health guidance by portable computer]. PMID- 1895543 TI - [Distribution of 14C-formaldehyde in pregnant mice: a study by liquid scintillation counter and binding to DNA]. PMID- 1895544 TI - Pathogenesis and treatment of lupus nephritis. PMID- 1895545 TI - Pathogenesis of glomerulosclerosis: current concepts. PMID- 1895546 TI - Growth hormone treatment for patients with renal failure. PMID- 1895547 TI - Soluble IL-2 receptor in patients with primary nephrotic syndrome. AB - The soluble interleukin-2 receptor (SIL-2R) levels in 46 patients with primary nephrotic syndrome were examined. The values in the nephrotic patients exceeded those in healthy controls (p less than 0.05), and were the same at the nephrotic and non-nephrotic stages. The serum interleukin-2 (IL-2) levels in the nephrotic patients were low and did not correlate with the serum SIL-2R levels. Only at the nephrotic stage were the latter closely correlated with the serum IgG (p less than 0.001) but not with the serum IgA or IgM. The SIL-2R production by phytohemagglutinin stimulated peripheral blood lymphocytes (PBL) in the nephrotic patients was less at the nephrotic and non-nephrotic stages than that in the healthy controls. The IgG production by pokeweed mitogen stimulated PBL was low at the nephrotic stage but not at the non-nephrotic stage. Based on these findings, it is suggested that SIL-2R determinations should prove useful in clarifying the relationship between cellular and humoral immunological disorders in nephrotic syndrome. PMID- 1895548 TI - Thromboelastographic analysis of coagulation and fibrinolysis in rats with nephrotic syndrome induced by daunomycin. AB - Thromboelastography was carried out to examine the coagulation and fibrinolytic systems in experimental nephrotic rats following treatment with daunomycin. The daunomycin rats showed augmentation of ma on thromboelastography. The response to the plasminogen activator, urokinase, on thromboelastography differed between the daunomycin and control rats. Most daunomycin rats failed to reveal any fibrinolytic effect of urokinase on thromboelastography. Experimental nephrotic rats induced by daunomycin may thus possibly develop hypercoagulability and exhibit a depressed fibrinolytic activity. PMID- 1895549 TI - Different appearance and pathogenic roles of serum IgA against autologous IgG Fc and Fab in patients with IgA nephropathy. AB - The serum levels of IgA class antibodies against autologous IgG Fc and Fab fragments were measured by ELISA in 62 patients with primary IgA nephropathy (IgAN) and 20 normal healthy volunteers. Both antibodies were significantly higher in the patients (P less than 0.01). The total IgA levels were correlated with those of IgA anti-IgG Fc antibodies (IgA anti-Fc) (rs = 0.57, P less than 0.001), but not with those of the IgA anti-IgG Fab antibodies (IgA anti-Fab). A histopathological comparison revealed that the sera of patients with severe glomerulonephritis had significantly higher levels of IgA anti-Fc than those with milder lesions (P less than 0.01). On the other hand, no correlation was observed between the serum levels of IgA anti-Fab and the histopathological severity. A comparison before and after treatment in 12 patients demonstrated a significant decrease of IgA anti-Fc (P less than 0.01) and an increase of IgA anti-Fab (P less than 0.05) after the treatment. Size analysis in serial sera from 3 patients was performed using HPLC under neutral (pH = 7.0) and under acid (pH = 3.5) buffer conditions. A markedly increased ratio of both antibodies with the polymeric form was observed in the active phase. In the remission phase, the amounts of acid-dissociable polymeric form IgA anti-Fc were decreased. In contrast, high levels of polymeric form IgA anti-Fab continued to be observed in 2 patients at this phase. These results suggest that abnormally stimulated production of IgA class autoantibodies especially with the polymeric form against both IgG Fc and Fab fragments, occurs in IgAN, involving separate regulation with differing reactions to treatment and a distinct relationship between IgA anti-Fc and active histopathological lesions. PMID- 1895550 TI - Effect of an oral adsorbent (AST-120) in rats with daunomycin-induced chronic renal failure. AB - The effect of an oral adsorbent (AST-120) was examined in rats with daunomycin induced chronic renal failure. Sixteen pairs of daunomycin rats which had similar levels of proteinuria at 4 weeks after being injected with daunomycin were selected. One rat of each pair served as a control and was fed on a standard diet, while the other rats were fed on a diet containing AST-120. The blood creatinine and blood urea nitrogen (BUN) were significantly lower in the rats fed with AST-120 than in the controls. Moreover, the life span of the rats fed with AST-120 was significantly prolonged as compared to that of the control rats. These findings suggest that oral administration of AST-120 may help to prevent rapid deterioration of renal function in experimental chronic renal failure induced by daunomycin in rats. PMID- 1895551 TI - Membranous nephropathy with crescents in rheumatoid arthritis: a case report. AB - A 59-year-old man with long-standing rheumatoid arthritis (RA) developed renal dysfunction, proteinuria and hematuria. Neither gold nor penicillamine had been given. Light microscopy of a renal biopsy specimen revealed membranous nephropathy with crescents of various stages. The possible pathogenesis of such an unusual combination of membranous nephropathy and crescents in RA is discussed. PMID- 1895552 TI - A case of primary systemic amyloidosis with AA protein. AB - We present here a case of young adult-onset primary systemic amyloidosis with AA protein. A 29-year-old male presenting with macrohematuria was transferred to our hospital because of aggravation of renal function. Amyloid protein was detected in the bladder, stomach and thyroid. The amyloid protein proved to be AA type by potassium permanganate histochemical analysis. Since secondary amyloidosis was excluded by the laboratory data and there was no family history of amyloidosis, a diagnosis of primary systemic amyloidosis with AA protein was reached. Although the patient was prescribed dimethyl sulphoxide, his renal function worsened with gastrocolic symptoms and a bleeding tendency. Hemodialysis (HD) was then initiated. After starting the HD, the patient's general condition recovered and subsequently the patient on treatment with maintenance HD was discharged. PMID- 1895553 TI - Pharmacokinetics and optimum dose of disopyramide in patients with chronic renal failure. AB - The pharmacokinetics and optimum dose for maintenance of disopyramide (DP) which is effective against arrhythmia were studied in patients with chronic renal failure (CRF, n = 10), who had a creatinine clearance (Ccr) less than 30 ml/min. The plasma concentrations (PC) of DP and mono-isopropyl-disopyramide (MDP) an active metabolite of DP, were measured by high performance liquid chromatography. Samples from patients and controls were obtained at 0, 1, 2, 3, 4, 6, 8, 12, 24, 33, and 48 hr after oral administration (OA) of 100 mg DP. The pharmacokinetic parameters were calculated using a two-compartment model. In CRF, the plasma half life (T 1/2) of DP was 5.25 to 22.42 hr (average is 12.45 hr) and that of MDP was 5.09 to 131.66 hr (average is 16.9 hr). In normal controls, the T 1/2 of DP was 6.05 hr, but that of MDP could not be determined the available sensitivity of measurement. T max was 3.11 hr at the total PC of DP and MDP, and C max was 2.48 g/ml on average. In conclusion, the present study revealed that: (1) the PC of a mixture of DP and MDP should rise following OA of DP every 8 or 12 hr in CRF; (2) it is necessary therefore to monitor the accumulation of MDP after rolling OA of DP; and (3) OA of DP every 24 hr can maintain an effective PC. PMID- 1895554 TI - [Pulmonary inhalation scintigraphy using N-isopropyl-p-[123I]iodoamphetamine (123I-IMP) aerosol]. AB - N-isopropyl-p-[123I]iodoamphetamine (123I-IMP) is lipophilic substance and permeates through the alveolar epithelium via intracellular transport, whereas 99mTc-DTPA is water-soluble substance and permeates through the alveolar epithelium via paracellular transport. We performed inhalation lung imaging using 123I-IMP and 99mTc-DTPA in order to assess alveolar epithelial permeability in 4 patients with restrictive ventilatory impairment, and 5 volunteers including one smoker. The time-activity (T/A) curves of 123I-IMP were well fitted into two compartments, first and slow, by least-squares fit technique, in contrast to 99mTc-DTPA fitted well with one compartment. In 4 normal volunteers, the T/A curves of the lower pulmonary fields declined faster than those of other pulmonary fields. In 99mTc-DTPA studies, the Kep values of patients with restrictive ventilatory impairment (n = 4) were higher than those of normal volunteers (n = 4) (2.14 +/- 0.30 x 10(-4) vs 1.48 +/- 0.41 x 10(-4), p less than 0.005). On the other hand, in 123I-IMP studies, the Kep values of the patients were much lower than those of normal volunteers (6.79 +/- 0.55 x 10(-5) vs 1.52 +/- 0.45 x 10(-3), p less than 0.005). PMID- 1895555 TI - [Evaluation of left ventricular function using gated planar myocardial imaging with Tc-99m-MIBI]. AB - A quantitative index of left ventricular wall motion obtained from ECG-gated planar myocardial images has been developed. Five normal controls and 39 patients with heart disease received an injection of Tc-99m-MIBI (550-740 MBq) at rest, and ECG-gated planar scintigraphy (LAO view) was performed 3 h later. Mean End diastolic (ED) and end-systolic (ES) myocardial activities were measured using circumferential profile analysis and %count increase (CI) was determined according to the following formula; (ES count-ED count)/(ED count) x 100. The global %CI was compared with the EF obtained from contrast ventriculography (LVG; n = 29) and radionuclide ventriculography using Tc-99m-labelled RBC (RNV; n = 24). The regional %CI was compared with left ventricular wall motion assessed by LVG. The global %CI was correlated well with EF by LVG (r = 0.70) and EF by RNV (r = 0.75). The regional %CI significantly decreased in accordance with wall motion on LVG worsened at impaired region. In conclusion, gated perfusion imaging with Tc-99m-MIBI provides useful information on ventricular function in addition to myocardial perfusion. PMID- 1895556 TI - [Cerebral perfusion scintigraphy in patients with cerebrovascular disease by using 99mTc-ECD: comparative study with 123I-IMP SPECT]. AB - 99mTc-ECD SPECT was performed in 19 patients with cerebrovascular disease, and location, extent, and severity of the lesions on 99mTc-ECD SPECT were compared with those on 123I-IMP SPECT. The initial brain uptake was 5.5 +/- 0.7% of the injected dose at 10 minutes after injection, 5.3 +/- 1.3% at 90 minutes, and clearance from the brain is slow. The distribution in the brain was changed, especially washout from the thalamus was slower than that from other regions. The count ratio of perfusion defect to normal area (D/N) on 99mTc-ECD SPECT was unchanged over the time, and had no significant differences from that on 123I-IMP SPECT. 99mTc-ECD SPECT was superior in detection of the lesion in the basal ganglia, and showed the images with superior spatial resolution due to physical characteristics of 99mTc. However, mild ischemic lesion and peri-infarct area was not clearly visualized, while 123I-IMP SPECT could demonstrate these lesions with better contrast. PMID- 1895557 TI - [A bull's eye subtraction polar map for assessing thallium redistribution (1). Comparison with quantitative redistribution]. AB - A new bull's eye subtraction polar (BS) map has been developed for quantitative assessment of redistribution on stress-delayed thallium-201 SPECT studies. BS map was created after subtraction of a normalized stress bull's eye polar map from a normalized delayed polar map in 10 normal subjects and 33 patients with coronary artery disease to compare BS map with qualitative redistribution scores. The BS map showed less than 15% in all of the 50 segments in the normal subjects. Of 27 segments exhibiting persistent defect without redistribution, the BS map showed less than 10% in 20 segments (74%) and 10-15% in 6 segments (22%). On the other hand, of 34 segments exhibiting redistribution, the BS map showed greater than or equal to 15% in 25 segments (74%) and 10-15% in the remaining 9 segments (26%). Thus, significant redistribution was evident in the areas showing greater than or equal to 10-15% on the BS map. We conclude that the BS map is valuable for quantitative assessment of redistribution on stress-delayed thallium-201 SPECT imaging. PMID- 1895558 TI - [Scintigraphic diagnosis of postinfarction left ventricular aneurysm and the prediction of the residual left ventricular function after aneurysmectomy using ECG gated blood pool SPECT]. AB - The diagnostic accuracy of ECG gated blood pool SPECT (blood pool SPECT) for detecting and quantify postinfarction left ventricular aneurysm (LVA) was assessed in 49 patients with myocardial infarction and 15 control subjects. LVA, which was detected in 35 of 49 patients, was defined as a regional protrusion through a cardiac cycle in contrast ventriculography and as a non-contracting segment with a markedly delayed phase angle in the tomographic functional images derived from phase analysis. The blood pool SPECT technique showed a high sensitivity (100%), specificity (78.6%) and accuracy (93.3%) for detecting LVA and was very useful for precisely determining LVA location and sizing contractile and non-contractile volume of left ventricle in patients with LVA. Furthermore, left ventricular ejection fraction (LVEF) after the excision of LVA was predicted using preoperative pool SPECT images in 9 patients. The predicted LVEF was closely correlated with the measured LVEF after the operation (y = 1.09x-4.37, r = 0.87, p less than 0.01). Thus, gated blood pool SPECT can be a useful non invasive technique not only for detecting and quantifying left ventricular aneurysm but also for predicting a residual left ventricular function after aneurysmectomy. PMID- 1895559 TI - [Adrenocortical scintigraphy to evaluate incidental adrenal mass (incidentaloma) discovered on computed tomography]. AB - To assess the nature of adrenal mass incidentally discovered on computed tomography, adrenocortical scintigraphy with I-131-6 beta-iodomethyl-19 norcholest-5(10)-en-3 beta-ol (I-131 Adosterol) in 29 patients was retrospectively reviewed. All patients had no clinical symptoms and biochemical evidence of adrenal hyperfunction. Six of them had extra-adrenal malignancy. Increased tracer uptake on the side of adrenal mass was observed in 13 patients (concordant group): cortical adenoma in 8, macronodular hyperplasia in 1, no growing tumor in 1, and no further examination in the remaining 3 patients. No cancer patients were included in the concordant group. Symmetric uptake was seen in 9 patients (symmetric group): 1 cortical adenoma and 1 ganglioneuroma, 6 no growing tumor (two of them had malignancy), and no further examination in 1 patient. Decreased uptake were shown in 7 patients (dis-concordant group): metastasis in 4, adrenal cyst in 2, and no growing tumor in 1. Adrenocortical scintigraphy was helpful in distinguishing benign functioning adrenal masses from non-functioning adrenal masses such as metastatic tumor and cyst. PMID- 1895560 TI - [Evaluation of efficacy of PTCA in patients with angina pectoris by exercise Tl 201 myocardial SPECT]. AB - Exercise 201Tl single photon emission computed tomography (Ex-SPECT) was performed before and after percutaneous transluminal coronary angioplasty (PTCA) to detect ischemia and determine the response of the ischemic myocardium. In a series of 132 patients with angina pectoris, 43 were followed up by Ex-SPECT and coronary angiography. Before PTCA, ischemia was detected in 85% of the patients, and in all cases a diameter stenosis (%DS) of 90% or more was seen. After PTCA, 90% of the patients showed improvement of ischemia. An excellent correlation between the pressure gradient (PG) as determined during PTCA and the washout rate (WR) suggests that the WR can be used as a measure for myocardial perfusion in the areas related to coronary stenosis. During follow-up by Ex-SPECT, 34 patients were found with redistribution, and restenosis was present in 59% of these patients. In comparison with the images obtained one week after PTCA, a further improvement was confirmed by Ex-SPECT during follow-up in 5 of 20 patients without restenosis. Ex-SPECT proved to be of use in evaluating the response of the ischemic myocardium to PTCA, as well as the therapeutical effects and the degree of restenosis. Long-term follow-up revealed that some patients had areas of hibernating myocardium. PMID- 1895561 TI - [Radionuclide cavography before and after percutaneous transluminal angioplasty in Budd-Chiari web: case report]. AB - A case of the Budd-Chiari syndrome due to a web of the hepatic inferior vena cava (IVC) is reported. A 54-year-old male with mild liver dysfunction was suspected with IVC obstruction from the screening CT which revealed liver cirrhosis with marked caudate lobe enlargement and dilatation of azygous and hemiazygous vein. Subsequent radionuclide cavography with 99mTc-HSA clearly demonstrated IVC obstruction, but failed to clarify the site or type of the obstruction. Finally contrast cavography diagnosed a web of the hepatic IVC, which was treated by percutaneous transluminal angioplasty (PTA). During two-year follow-up after PTA none of the radionuclide cavographies showed reocclusion of the IVC and as a result contrast cavography was avoided. Radionuclide cavography, therefore, was a useful method for evaluating IVC obstruction before and after PTA for the Budd Chiari web. PMID- 1895562 TI - [An assay for circulating 1,25-dihydroxy-vitamin D employing purification with a mini-column--comparison with a method using purification by high performance liquid chromatography]. PMID- 1895564 TI - Mitochondrial DNA analysis of Leber's hereditary optic neuropathy. AB - A mitochondrial DNA (mtDNA) mutation associated with Leber's hereditary optic neuropathy (LHON) was recently observed. The presence or absence of the mutation was analyzed in 10 Japanese patients whose clinical course and fundus findings were consistent with LHON. Four of them had at least one maternally related individual who also had bilateral optic atrophy, and were diagnosed as "definite LHON". The other 6 cases lacked any record of optic nerve disease in maternally related individuals, and were diagnosed as "possible LHON". We found the mutation at the SfaNI site of mtDNA in 3 out of the former 4 cases, and in 5 out of the latter 6 cases. This result demonstrates the clinical and diagnostic importance of mtDNA analysis, especially with possible cases of LHON, and suggests that an alternative mutation associated with LHON is also present in Japanese patients. PMID- 1895563 TI - [A fundamental study of Diamox load scintigraphy using 99mTc-HM-PAO]. PMID- 1895565 TI - A projection of the lens accommodation-related area to the pupillo-constrictor area in the posteromedial lateral suprasylvian area in cats. AB - The fiber connection between areas related to lens accommodation and to pupillary constriction was studied in the posteromedial lateral suprasylvian area (PMLS) in the extrastriate cortex of the cat. The accommodation-related area was located in the PMLS by microstimulation, and the anterograde tracer Phaseolus vulgaris leucoagglutinin was injected into this area. Anterogradely-labeled fibers and terminals were found in the upper part of the medial bank of the middle suprasylvian sulcus, the area corresponding to the pupillo-constrictor area in the PMLS. The labeling was also found in the fundus of the middle suprasylvian sulcus, the medial bank of the lateral sulcus and the superficial layers of the superior colliculus. It is concluded that the area related to lens accommodation projects to the area related to pupillary constriction in the PMLS. PMID- 1895566 TI - In vivo lectin-binding of photoreceptors and interphotoreceptor matrix in rat. AB - The in vivo distribution of lectin receptors in the photoreceptors and interphotoreceptor matrix (IPM) was studied by histochemistry and light microscopy. Horseradish peroxidase-conjugated lectins (peanut agglutinin, PNA; Ricinus communis agglutinin-1, RCA-1; or wheat germ agglutinin, WGA) were administered into the subretinal space of living rats, and 1 and 6 hours later eyeballs were enucleated to examine retinal tissues with a light microscope. The surfaces of cone photoreceptor outer segments and inner segments, and/or cone associated IPM were labeled preferentially with PNA at 1 and 6 hours after its subretinal administration. One hour after subretinal injection, RCA-1 labeling appeared in the distal surface of the outer segments, the basal region of the inner segments, and the surface of the retinal pigment epithelium (RPE). At 6 hours the basal portion of the outer segments showed RCA-1 labeling as well. The distribution of labeling by WGA was uniform throughout the outer segments and/or the IPM domain except for the most distal portion of the outer segments. These observations conform for the most part to previous in vitro experiments, and indicate, together with previously not explicitly described observations, that a spatial heterogeneity in the vertical and horizontal directions exists in the IPM domain. PMID- 1895567 TI - Immunoelectron microscopic observation of cells in the rat retinal containing gamma-aminobutyric acid and catecholamine. AB - Interactions between gamma-aminobutyric acid (GABA)- and catecholamine (CA) containing cells in the rat retina was revealed by a double-labeling immunocytochemical technique using the antisera to GABA- and CA-synthesizing enzymes, such as tyrosine hydroxylase (TH) and phenylethanolamine-N methyltransferase (PNMT). At the light microscopic level, GABA-, TH- and PMNT immunoreactive (GABA-, TH- and PMNT-IR) amacrine cell bodies and their processes appeared in the inner nuclear layer and the inner plexiform layer, respectively. By electron microscopy observation, in the inner plexiform layer, GABA-, TH- or PMNT-IR amacrine cell processes were found making synaptic contacts with the axon terminals of immunonegative bipolar cells or with the processes of immunonegative amacrine cells. TH-IR amacrine cell processes formed synapse-like contacts with the GABA-IR amacrine cell perikarya and processes. In contrast, GABA-IR amacrine cell processes formed symmetric synaptic contacts onto the TH-IR as well as PNMT IR amacrine cell processes. From these findings, it appears that the GABA- and CA containing amacrine cells may interact with each other and play some important role in regulating the activities of bipolar cells and other unknown amacrine cells in the rat retina. PMID- 1895568 TI - Distribution of chloride ion in intercellular space of retinal pigment epithelium -effects of various agents. AB - The distribution of chloride ion (Cl-) in the frog retinal pigment epithelium (RPE) was investigated histologically to determine the effects of various agents on the Cl- concentration in the intracellular spaces of the RPE. Fixation with osmium tetroxide containing silver acetate resulted in the deposit of silver chloride (AgCl) in the RPE, and this was confirmed by X-ray microanalysis. The Cl concentration in the intercellular space decreased significantly after the fixation and washing with sucrose solution before Cl- deposition procedures, as well as after the 2,4-dinitrophenol treatment, which inhibits the active transport mechanism of the RPE. The intercellular Cl- concentration decreased after the cyclic AMP or cyclic GMP treatment which, respectively, decreases or might decrease Cl- transport from the apical to the basolateral side of the RPE. The Cl- concentration in the intercellular spaces did not change after the ouabain treatment. The results of the present study suggest that the changes in the Cl- concentration in the intercellular spaces of the RPE are related to the status of Cl- transport in the RPE. PMID- 1895569 TI - Adoptive transfer of experimental autoimmune uveoretinitis induced by interphotoreceptor retinoid-binding protein. AB - The immunopathogenic mechanisms of experimental autoimmune uveoretinitis (EAU) induced by interphotoreceptor retinoid-binding protein (IRBP) were studied. Lymph node (LN) cells or spleen cells were collected from donor rats 14 days after the immunization with IRBP. After the 3-day pre-incubation of these cells with either IRBP or Concanavalin A (Con A), the cells were transferred to naive syngeneic rats intraperitoneally. EAU was successfully transferred by LN cells pre-cultured with IRBP, while EAU was poorly transferred by LN cells pre-cultured with Con A. On the other hand, spleen cells pre-cultured with either IRBP or Con A were quite potent to transfer EAU. In addition, the enriched helper/inducer T-cells repeatedly transferred EAU, while the enriched suppressor/cytotoxic T-cells did not. There also existed the simultaneous involvement of pinealitis. The histopathological features of EAU and pinealitis were generally similar to those in actively immunized rats. The immune responses to IRBP in recipients with EAU were mostly cellular (delayed hypersensitivity type skin response and proliferative responses of lymphocytes), while humoral responses (Arthus type skin response and antibody activities) were quite weak in most of the recipients. Thus, it was confirmed that cellular immunity plays a major role in the adoptive transfer of EAU by IRBP as in S-antigen-induced EAU. PMID- 1895570 TI - Effects of intraocular irrigating solutions on the spreading of rabbit corneal endothelial cells on extracellular matrices. AB - The effects of four commercially available irrigating solutions on the spreading of rabbit corneal endothelial cells on various extracellular matrices were studied. Cultured rabbit corneal endothelial cells, suspended in one of the following intraocular irrigating solutions, Opeguard MA, BSS, BSS Plus, lactated Ringer solution (Lactec) or physiological saline, were placed on uncoated tissue culture plates or on plates coated with extracellular matrices (fibronectin, laminin, collagen type I, or collagen type IV). The cell area was measured after 45 minutes' incubation. The cells spread on all of the extracellular matrices examined but not on the uncoated tissue culture plates. On the fibronectin or laminin matrix, the cell area was significantly greater with Opeguard MA or BSS Plus. On laminin and collagen type IV, the cell area was the greatest with Opeguard MA. On collagen type I, the cell area was significantly greater with Opeguard MA, BSS, or BSS Plus. These results demonstrated that the rabbit corneal endothelial cells responded to the extracellular matrices, and that Opeguard MA or BSS Plus provided more favorable conditions for the spreading of these cells. These results indicated that both Opeguard MA and BSS Plus might aid the spreading of corneal endothelial cells during wound-healing immediately after intraocular surgery. PMID- 1895571 TI - Experimental autoimmune uveoretinitis in brown Norway rats induced by bovine interphotoreceptor retinoid-binding protein and renal cryosurgery. AB - In Brown Norway (BN) rats, it is known to be difficult to induce experimental autoimmune uveoretinitis (EAU) by the injection of retinal S-antigen (S-Ag) or interphotoreceptor retinoid-binding protein (IRBP) together with complete Freund's adjuvant (CFA), unless intravenous Bordetella Pertussis is used as an additional adjuvant. In the present study it was found that the rate of onset of EAU could be increased in BN rats immunized with IRBP and CFA by simultaneous cryosurgery to the renal cortex. There was no evidence of retinal vasculitis, pinealitis or nephritis in the rats with EAU except for renal inflammatory infiltrates as a reaction to the cryosurgery. Affected eyes eventually showed destruction of most retinal components and prominent infiltration of the retina by macrophages, with the changes being more severe than those previously reported in Lewis rats with EAU induced by IRBP. Data suggesting the existence of an antibody that cross-reacts with the proximal renal tubules and the retinal pigment epithelium were also obtained. PMID- 1895572 TI - Immunohistochemical study of deposits on intraocular lenses explanted from human eyes. AB - Immunohistochemical studies of deposits were carried out on two intraocular lenses (IOLs) explanted from human eyes. One anterior chamber intraocular lens (AC-IOL) was studied using a monoclonal anti-human type I collagen-peptide antibody (C-Ab). One posterior chamber intraocular lens (PC-IOL) was studied using a monoclonal anti-human vimentin antibody (V-Ab). Most of the cells on the AC-IOL contained many melanin granules in the cytoplasm and were thought to be macrophages. They did not show any immunoreactivity to C-Ab. Some spindle-shaped cells and fibrous deposits at the margin of the lens optics showed immunoreactivity to the antibody. These cells were thought to be fibroblasts migrating from the tissue around the IOL, such as the iris. On the PC-IOL, many mononuclear cells and multinucleated giant cells were observed. These cells showed immunoreactivity to vimentin and contained immunostained fibers which were intermediate filaments. They were thought to be either of mesodermal origin or derived from the lens epithelium. PMID- 1895573 TI - Stimulatory effect of N-[4-[2-(dimethylamino)-ethoxy] benzyl]-3,4 dimethoxybenzamide hydrochloride (HSR-803) on normal and delayed gastrointestinal propulsion. AB - To estimate the effect of a new gastroprokinetic agent, N-[4-[2 (dimethylamino)ethoxy]benzyl]-3,4-dimethoxybenzamide hydrochloride (HSR-803), on non-ulcer dyspepsia, the influence of HSR-803 on gastrointestinal propulsion was assayed in dogs, rats and mice in comparison with some gastroprokinetic agents. HSR-803 (30 mg/kg, p.o.) significantly enhanced gastric emptying in dogs, and it significantly improved the delayed gastric emptying induced by dopamine (0.4 mg/kg, i.p.) and morphine (1 mg/kg, s.c.) in rats. Metoclopramide (30 mg/kg, p.o.) also significantly restored the dopamine-induced delay, but at a dose of 10 mg/kg, p.o., it enhanced the morphine-induced delay in gastric emptying in rats. HSR-803 (10-100 mg/kg, p.o.) increased small intestinal transit in mice in a dose dependent manner, and the effect was abolished by atropine (0.3 mg/kg, i.p.). Metoclopramide also increased small intestinal transit, but domperidone and cisapride had no effect. In delayed small intestinal transit in mice, HSR-803 (10 100 mg/kg, p.o.) improved the morphine (0.3 mg/kg, s.c.)-induced delay in a dose dependent manner. In conclusion, because of the promotion of normal and delayed gastrointestinal propulsion, HSR-803 seems to be a promising gastroprokinetic agent for the treatment of non-ulcer dyspepsia. The action of HSR-803 is likely to be exerted through cholinergic stimulation. PMID- 1895575 TI - NMDA induces protein kinase C translocation in guinea pig cerebral synaptoneurosomes. AB - N-methyl-D-aspartate (NMDA)-induced translocation of protein kinase C from the cytosol to membrane fractions was examined by the [3H]phorbol 12,13-dibutyrate (PDBu) binding method in guinea pig cerebral synaptoneurosomes. Pretreatment of synaptoneurosomes with NMDA, but not that with quisqualate or kainate, induced changes in the distribution of [3H]PDBu binding in the cytosol and membrane fractions in a dose-dependent manner. The NMDA-induced changes of the binding were completely dependent on Ca2+ and inhibited by NMDA receptor antagonists Mg2+, 2-amino-5-phosphonovaleric acid and ketamine, but not by Zn2+. Glycine slightly potentiated the NMDA-induced changes of [3H]PDBu binding. NMDA stimulated Ca2+ uptake but not the phosphoinositide hydrolysis in the synaptoneurosomes. These results suggest that NMDA enhances Ca2+ influx through receptor-operated Ca2+ channels, increasing intracellular calcium concentration and thereby induces translocation of protein kinase C. PMID- 1895574 TI - Effect of a new calcium entry blocker, NB-818, on delayed neuronal death in the ischemic gerbil hippocampus. AB - The effect of NB-818, a new dihydropyridine calcium entry blocker, on delayed neuronal death (DND) in the hippocampal CA1 subfield of gerbils after 5 minutes of forebrain ischemia induced by bilateral carotid artery occlusion was examined. Gerbils were treated intraperitoneally with NB-818 (0.1-3 mg/kg) just after release of the occlusion. Four days after the ischemia, they were fixed by perfusing 10% buffered-formalin, and the neuronal cell density (NCD, cell/mm) in the CA1 subfield was estimated under microscopy. The average NCD in the ischemic control group was 43 +/- 10.8 cells/mm, whereas NB-818 (3 mg/kg) significantly ameliorated DND with an average NCD of 143 +/- 24.2 cells/mm (P less than 0.01). In addition, NB-818 (3 mg/kg) significantly inhibited DND at 1, 2 and 4 weeks after transient ischemia: the average NCD of the NB-818 and ischemic control groups were 80 +/- 9.4 (P less than 0.01) and 43 +/- 7.7 cells/mm, 92 +/- 13.7 (P less than 0.05) and 52 +/- 9.3 cells/mm, and 57 +/- 5.0 (P less than 0.01) and 43 +/- 12.4 cells/mm, respectively. In this experiment, NB-818 exhibited a protective effect on DND in the hippocampal CA1 subfield after transient forebrain ischemia, and its effect persisted for up to 4 weeks. These findings suggest that NB-818 may be useful for clinical treatment of neurological deficit after an ischemic insult. PMID- 1895576 TI - Working memory deficit in aged rats in delayed nonmatching to position task and effect of physostigmine on performance of young and aged rats. AB - Young (5 month) and aged (23 month) male rats were tested in delayed nonmatching to position task using a T-maze, and their ability of working memory retention was assessed over interrun intervals ranging between 5 and 300 sec. There were no significant age differences in pretest performance at 0 sec interval, but significant memory loss was observed in aged rats when tested with the interrun intervals. Physostigmine (0.1 and 0.2 mg/kg) improved this age-related decline in working memory in a dose-dependent manner, whereas the treatment slightly but not significantly improved the performance of young rats. These results suggest that the central cholinergic system in aged rats was functionally deteriorated and that stimulation of the system could enhance working memory retention in aged rats. PMID- 1895577 TI - Some correlations between local anesthetic-induced convulsions and gamma aminobutyric acid in rat spinal cord. AB - The effects of local anesthetics (procaine and lidocaine) on the gamma aminobutyric acid (GABA) and L-glutamic acid (Glu) levels in rat spinal cord were studied during the convulsive process. The present study also investigated the influence of central GABA manipulations on the local anesthetic-induced convulsions. An increase in spinal GABA levels was observed at the preconvulsive and convulsive states after administration of procaine (170 mg/kg, i.p.) or lidocaine (120 mg/kg, i.p.), which induced clonic convulsions; in the depressive state, GABA levels returned to normal; in all states, Glu levels were unchanged. Semicarbazide (25-100 mg/kg, i.p.), a glutamic acid decarboxylase inhibitor, produced a decrease in spinal GABA content and strongly enhanced both local anesthetic-induced convulsions as shown by a shortening of the latency and an increase in the mortality. Aminooxyacetic acid (AOAA; 10-40 mg-kg, i.p.), a GABA transaminase inhibitor, dose-dependently increased spinal GABA content and markedly suppressed procaine-induced convulsions. However, lidocaine-induced convulsions were enhanced by AOAA. These results suggest that the spinal GABA neuron may respond to the convulsions induced by local anesthetics. Furthermore, there is a clear relationship between spinal GABA content and procaine-induced, but not lidocaine-induced, convulsions. PMID- 1895578 TI - Presynaptic sites of isolated canine saphenous veins are more sensitive to protein kinase C than postsynaptic ones. AB - Effects of protein kinase C (PKC) activators and inhibitors on both tritium overflow and contraction evoked by 40 mM KCl were studied in canine saphenous veins preloaded with [3H]norepinephrine (NE). 12-O-Tetradecanoylphorbol 13 acetate (TPA) and phorbol 12,13-dibutyrate (PDBu) at 10(-11)-10(-7) M enhanced concentration-dependently the KCl-evoked tritium overflow, which was antagonized by polymyxin B (10(-5) M) and staurosporine (10(-7) or 10(-6) M). PDBu (10(-8) and 10(-7) M), but not TPA, potentiated the KCl-induced contraction. Only staurosporine reduced the KCl-induced contraction in the presence of PKC activators. Polymyxin B (3 X 10(-5) M) which failed to inhibit exogenous NE induced contraction attenuated both responses to KCl. Staurosporine (10(-6) M) suppressed not only both the responses to KCl but also exogenous NE-induced contraction. Phentolamine (10(-6) M) inhibited almost completely the KCl-induced contraction and augmented remarkably the evoked tritium overflow. PDBu (10(-8) and 10(-7) M) still potentiated both responses to KCl in the phentolamine-treated veins. An additional treatment with nifedipine (10(-6) M) inhibited markedly the potentiation of the KCl-induced contraction by PDBu in the presence of phentolamine without affecting the evoked overflow. These results suggest that PKC may modulate KCl-evoked NE release from the adrenergic nerve endings of canine saphenous veins and that PKC is more sensitive to presynaptic than postsynaptic sites. PMID- 1895579 TI - Protective effect of vinpocetine against brain damage caused by ischemia. AB - The effects of vinpocetine against hippocampal neuronal damage and on local cerebral blood flow (LCBF) were examined in a rat model of forebrain ischemia (10 min occlusion of the carotid arteries and hypotension). Histological evaluation of neuronal loss in the hippocampus was performed 7 days after ischemia. LCBF was measured before ischemia as well as after 2 min and 1 hr of recirculation. Vinpocetine (10 mg/kg) administered pre- or post-ischemically reduced the hippocampal neuronal necrosis, while pre-ischemic administration of 2 or 20 mg/kg vinpocetine was ineffective. Since vinpocetine increased the LCBF after 1 hr of recirculation, it cannot be excluded that blood flow improvements contribute to its neuroprotective activity. On the other hand, there is no clear evidence that an elevation of post-ischemic hypoperfusion could protect neurons against ischemic damage. It is, therefore, suggested that vinpocetine acts directly on brain cells. PMID- 1895580 TI - Active principle of swine prostate extract: I. Isolation of active principle activating prostatic acid phosphatase and its effect on testosterone uptake of the prostate in castrated rats. AB - There have been several reports concerning the therapeutic effect of an extract from animal prostates on benign prostatic hypertrophy. Previously, we reported that the swine prostate extract (PE) had the activity to enhance human prostatic acid phosphatase (PAPase) activity in vitro, and to increase the muscular tonicity of the urinary bladder by directly acting upon vesical muscles, suggesting that PE have an activity to elevate the intravesical voiding pressure in vivo. In the present study, it was attempted to isolate such an active principle of PE as activates human prostatic acid phosphatase (PAPase). The finally purified PE (PPE) was assessed as to some physico-chemical and pharmacological properties. 1) PPE was found to be a peptide with a molecular weight of about 8,800, composed largely of neutral amino acids (approximately 70%) and few of aromatic amino acids. 2) PPE activated PAPase in a dose-dependent fashion, resulting in an increase of the enzyme activity approximately twice in a dose of 2 X 10(-5) g/ml of PPE. Furthermore, PPE recovered PAPase activity dose dependently from the 50% inhibition by 2 X 10(-3) M L-tartaric acid. 3) In castrated rats, the 3H-testosterone uptake of the prostate was significantly suppressed by the oral administration of PPE. PPE might be one of active principles of PE for the therapeutic effect on prostatic hypertrophy. PMID- 1895582 TI - Influence of sialoadenectomy on capsaicin-sensitive "gastric defense mechanism" in rats. AB - Chemical ablation of sensory afferents produced by the treatment with the neurotoxin capsaicin worsened gastric ulcers induced by 50% ethanol in sham- and sialoadenectomized (SALX)-operated rats. Conversely, capsaicin worsened water immersion stress (WIS)-ulcers in SALX, but not those in sham-operated animals. The concomitant removal of two potent antisecretory factors, such as salivary gland containing epidermal growth factor and neuropeptides contained in the sensory afferents, is probably responsible for the enhanced vulnerability of the mucosa in WIS-ulcers. PMID- 1895581 TI - Hemodynamic effects of benazeprilat in the anesthetized dog with acute left ventricular failure. AB - To examine the hemodynamic effects of benazepril, an angiotensin converting enzyme inhibitor, in left ventricular failure, its active metabolite benazeprilat was administered during acute ischemic left ventricular failure in anesthetized open chest dog induced by repeated injections of plastic microspheres into the left coronary artery. The coronary embolization with microspheres resulted in a moderate and stable left ventricular pump failure characterized by increased left ventricular end-diastolic pressure (LVEDP) and decreased cardiac output (CO). Benazeprilat (30 micrograms/kg) administered intravenously after a stabilization period lowered LVEDP and maintained CO. The total peripheral resistance was reduced with benazeprilat. The oxygen consumption and the coronary blood flow were reduced with benazeprilat because of a decrease in wall tension and afterload. These results suggest that benazeprilat (benazepril) has beneficial effects for the treatment of acute left ventricular failure. PMID- 1895583 TI - Lung vascular permeability enhanced by sympathetic nerve stimulation in rats. AB - Role of sympathetic nerves in increasing the lung vascular permeability was investigated in the presence of papaverine using an isolated rat lung perfusion preparation. Sympathetic nerve stimulation was performed at different time points before and after pressure-induced weight gain. When stimulated at 3 or 7 min after the pressure associated increment, stimulation evoked a further increase in lung weight, particularly in the former case. In contrast, stimulation performed before or 15 min after the pressure increment elicited no such response. The histological finding of carbon particles in the perivascular wall after sympathetic nerve stimulation also provided direct evidence of increased lung vascular permeability. PMID- 1895584 TI - [C5 contents and neutrophil chemotactic activities in bronchiolar and alveolar regions]. AB - To clarify the localization and mechanism of neutrophil infiltration in the lower respiratory tract, we measured neutrophil number, neutrophil chemotactic factor (NCF) activity and content of C5 in bronchial lavage (BL) fluid and bronchoalveolar lavage (BAL) fluid. Numbers of neutrophils, NCF activity and C5 content were higher in the BL fluid from normal volunteers (NV) and control patients (CP) than those in the BAL fluid from the same subjects. The NCF activity in the BL fluid was inhibited approximately 40% by anti-C5 antiserum, and correlated with C5 content in the BL fluid. In the BAL fluids of patients with chronic airway diseases (CAD) and patients with idiopathic interstitial pneumonia (IIP), neutrophil number, NCF activity and C5 content were increased compared to those in BAL fluid from NV or CP. These results indicated that neutrophils are predominant in the bronchial region compared to the alveolar region, and that C5-derived NCF play important roles in the accumulation of neutrophils in the bronchial region. Also C5-derived NCF are thought to be related to, at least, a part of the neutrophil infiltration in the respiratory tract of patients with CAD and IIP. PMID- 1895585 TI - [Liver disorders in patients with Mycoplasma pneumoniae pneumonia]. AB - Liver disorders were reviewed in 76 patients with mycoplasma pneumoniae pneumonia (MP) admitted to Kamo Hospital from 1979 to 1989. Liver dysfunction was detected in 16 patients (21%). Liver disorder were detected in 10% of MP from 1979 to 1980, but in 20% from 1984 to 1985, and in 36% from 1988 to 1989. By multiple regression analysis CRP was found to be the most significant factor among other factors such as prevalence, age, sex, history of smoking, history of drinking, and days after onset of fever. PMID- 1895586 TI - [Two cases of hypersensitivity pneumonitis due to contamination of an ultrasonic humidifier]. AB - Two cases of hypersensitivity pneumonitis due to contamination of ultrasonic humidifier were reported. The first case, a 64-year-old man, developed fever and dyspnea on exertion in January 1986. He was hospitalized for 18 days and received antibiotics for presumptive bacterial pneumonia. Half a day after discharge, those symptoms recurred. On readmission, fine crackles were heard at the left lung base, and chest X-ray film showed ground glass shadows all over the lung fields. Bronchoalveolar lavage (BAL) and transbronchial lung biopsy (TBLB) were performed on the next day after readmission. TBLB specimen revealed lymphocyte alveolitis, granulomatous tissue and infiltration of polymorphonuclear neutrophils (PMN) in alveoli. Differential cell count of the BAL fluid showed not only lymphocytosis (38.2%) but also increased PMNs (44.2%). In the second BAL performed 18 days later, the value of PMNs demonstrated a dramatic decrease. Environmental challenge tests revealed that his hypersensitivity pneumonitis was caused by an ultrasonic humidifier in his bed room. Immunological examinations showed positive Arthus type skin reaction and serum precipitin against Aspergillus fumigatus. Inhalation challenge with A. fumigatus produced cough and dyspnea with a decrease of 10 Torr in PaO2. These data suggest that A. fumigatus may be the causative antigen in this case. The second case, a 64-year-old man who had used ultrasonic humidifier in his living room, was admitted for 8 weeks with an illness characterized by cough, low fever and general malaise on 22 January 1987. Examination revealed fine crackles on both lung bases. Chest X-ray film demonstrated diffuse nodular shadows. The TBLB specimen showed lymphocytic alveolitis and bronchiolitis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1895587 TI - [Three cases of minocycline-induced pneumonitis]. AB - All three patients complained of cough, fever and dyspnea. Their chest X-ray films revealed interstitial changes such as Kerley B lines. The results of lymphocyte stimulation tests were all negative for Minocycline (MINO), whereas the provocation tests were all positive in three cases. The onsets of symptoms appeared 7, 12 and 9 hours after administration of MINO respectively, which suggested type III allergy in terms of the latency period. In cases No. 1 and No. 3, lung tissue specimens obtained by transbronchial biopsy showed findings of mild acute eosinophilic pneumonia. The bronchoalveolar lavage fluid of case No. 3 showed eosinophilia. On diagnosing MINO-induced pneumonitis, the lymphocyte stimulation test is not always beneficial, whereas the provocation test is supposed to be a safe and sure method. PMID- 1895588 TI - [Two cases of Ewing's sarcoma originating from the adult rib]. AB - Two cases of Ewing's sarcoma originating from the adult rib were reported. Case 1: A 23-year-old male was admitted for further examination of a right anterior chest wall tumor. The tumor was resected and the pathological examination revealed Ewing's sarcoma. Adriamycin, vincristine, cyclophosphamide and actinomycin-D were administered. After 1 year the patient died due to local relapse. Case 2: A 28-year-old male was found to have a left extrapleural tumor on chest roentgenogram. He responded to chemotherapy consisting of CDDP, etoposide, ifosfamide and radiotherapy at a dose of 38.4 Gy before surgery. On the surgical specimen no tumor cells were observed and his postoperative course has been good. According to our experience, exact preoperative diagnosis and adjuvant therapy are necessary to improve the prognosis of Ewing's sarcoma patient. PMID- 1895589 TI - [A case of exogenous lipoid pneumonia showing a coin lesion with cavities]. AB - A 26-year-old male was referred to our department because of an abnormal chest X ray, obtained during a routine physical examination in the hospital admitted after a traffic accident. The P-A chest film revealed a coin lesion with cavities in the left S9. He complained of no symptoms except for expectoration of bloody sputum. Transbronchial lung biopsy specimens showed destruction of normal alveolar pattern and collections of lipid-laden macrophages enclosed by fibrous tissue. The lipid material of macrophages in sputum was stained with Sudan III. He had no difficulty in swallowing and no history of regular use of oily drugs. Fiberoptic bronchoscopy and chest CT showed no obstruction of bronchi. He had been working in a repair shop for motorcycles for years, therefore the lesion could be an occupational exogenous lipoid pneumonia. The diameter of the coin lesion has decreased without any therapy. PMID- 1895590 TI - [Cellular interstitial pneumonia and follicular bronchiolitis diagnosed by open lung biopsy in a patient with rheumatoid arthritis]. AB - A 54-year-old woman under treatment for rheumatoid arthritis was admitted because of aggravation of dyspnea on effort and restrictive pulmonary dysfunction. Although chest X-ray revealed no marked change, the symptoms progressively worsened, necessitating open lung biopsy for diagnosis and treatment. Based on the histopathological findings of the biopsied tissue, the patient was diagnosed as having active rheumatoid lung complicated with cellular interstitial pneumonia and follicular bronchiolitis. The patient responded well to adrenocorticosteroid and immunosuppressor therapy, and is now being followed up as an outpatient. Rheumatoid arthritis can be complicated by diverse lung diseases. Among them one important disease is interstitial pneumonia, which serves as a prognostic factor. When cellular interstitial pneumonia is treated with adrenocorticosteroid therapy, it responds well and its prognosis is good. Therefore, its early detection and appropriate adrenocortical therapy are essential. Patients with rheumatoid arthritis presenting with dyspnea on effort and pulmonary dysfunction should be examined for cellular interstitial pneumonia, follicular bronchiolitis and other lung diseases, even when no marked change is visible on chest X-ray films. PMID- 1895591 TI - [Bronchoalveolar lavage studies in a HTLV-1-positive case associated with interstitial pneumonia]. AB - A 64-year-old housewife was hospitalized because of cough and dyspnea. Chest X rays on admission showed diffuse interstitial shadows and loss of lung volume, suggesting acute interstitial pneumonia. Pulmonary function tests revealed decreased vital capacity and severe hypoxemia. Bronchoalveolar lavage studies showed that total cell counts and a proportion of lymphocytes were increased. Lymphocytes increased in lavage fluid consisted mainly of T cells with an elevated CD4+/CD8+ ratio. Furthermore, these lymphocytes spontaneously proliferated and responded well to recombinant IL-2 when cultured in vitro for 5 days, suggesting that lymphocyte activation occurred in the lung. Such lavage findings and lymphocytes activation in association with the presence of HTLV-1 specific IgA antibody in lavage fluid have been demonstrated in patients with HTLV-1-associated myelopathy. In this patient positive for HTLV-1, however, it could not be determined whether the pulmonary lesions were primarily related to HTLV-1 infection, because no IgA antibody specific for HTLV-1 was demonstrated in lavage fluid. In conclusion, when pulmonary abnormalities are found in HTLV-1 carriers, we should be careful in determining whether such pulmonary involvements are etiologically related to HTLV-1 infection. PMID- 1895592 TI - [A case report and literature review of acute eosinophilic pneumonia]. AB - Although chronic eosinophilic pneumonia is a well-known disorder, acute eosinophilic pneumonia has not been as well described. We described the clinical features of two patients with acute eosinophilic pneumonia. The patients presented with an acute onset of high fever, severe hypoxemia and diffuse pulmonary infiltrates. Eosinophilic pneumonia was diagnosed by bronchoalveolar lavage and confirmed by transbronchial lung biopsy. We believe that we have described an acute type of eosinophilic lung disorder which can not be applied to Crofton's classification of PIE, so we reviewed previously reported cases of acute eosinophilic pneumonia and tried to summarize their clinicopathological features. We also emphasized the existence of eosinophil infiltration into the bronchial wall in Acute Eosinophilic Pneumonia. PMID- 1895593 TI - [A case of tuberculous osteomyelitis resembling metastatic cancer on bone scintigraphy]. AB - A 48-year-old male was referred to our division, on the suspicion of lung cancer with bone metastasis. Chest radiography showed a mass shadow and bone scintigram demonstrated multiple scattered regions of increased uptake. However bronchial and bone biopsy specimens revealed granuloma with epithelial cells and giant cells. A diagnosis of tuberculous osteomyelitis was made, and antituberculous therapy was begun. Chest radiography and bone scintigrams one year later showed marked improvement. PMID- 1895594 TI - [A case report of anomalous left brachiocephalic vein]. AB - An anomalous case of a left brachiocephalic vein passing behind the ascending aorta was observed in a 49-year Japanese man. This is known as anomalous left brachiocephalic vein. The anomalous left brachiocephalic vein descended along the left mediastinum in a position identical to that of a persistent left superior vena cava, so the diagnosis of this venous abnormally require carefully considered. Many cases of anomalous left brachiocephalic vein have been reported based on autopsy findings, but this venous anomaly was recently demonstrated by ultrasonography, CT, and MRI. PMID- 1895595 TI - [Special issue--simultaneous replacement of the aortic valve and the ascending aorta]. PMID- 1895596 TI - [Operative results of simultaneous replacement of aortic valve and ascending aorta]. AB - As a surgical treatment of ascending aortic aneurysm with aortic valve regurgitation, we employed Bentall's procedure in 6 cases, Cabrol's procedure in 6 cases, Cabrol's procedure in 3 cases and Carrel patch technique in 2 cases. No hospital mortality was recorded. Late complications were noted in 2 patients. A graft dehiscence of the anastomosis of the right coronary artery occurred in 1 patient with Cabrol's procedure, 3 months postoperatively. In another patient with Bentall's procedure, enlargement of the dissected false lumen at the distal aortic arch necessitated surgical repair in other hospital, 4 years and 4 months after primary repair. All of the surviving patients showed improvement in cardiac function and their clinical status. We have frequently experienced troublesome intraoperative bleeding in applying Bentall's procedure and Cabrol's procedure also. However, hemostatic control was permitted by Cabrol's trick. We are satisfied with the results obtained by Carrel patch technique. This technique facilitates secure coronary anastomosis and definitive hemostasis is attained. PMID- 1895597 TI - [Surgical treatment for aneurysms of the ascending aorta with aortic regurgitation: early and late results of simultaneous replacement of the aortic valve and the ascending aorta]. AB - From September 1976 to January 1991, 66 patients were operated on for aneurysms of the ascending aorta with aortic regurgitation. The indication for operation was annuloaortic ectasia in 40 patients (61%) and aortic dissection in 26 (39%). Twenty-seven patients (41%) had the classical Marfan syndrome. The surgical techniques employed in this series included separate graft valve replacement (separate G/V) in 18 patients whose coronary ostia were normally placed, and composite graft replacement with coronary reimplantation (composite G) in 48 patients whose coronary ostia were displaced cephalad by the aneurysm. Nineteen patients (29%) had the concomitant operative procedures including aortic arch replacement and mitral valve repair. The early death within one month after the operation occurred in 6 patients (9.1%) comprising 2 (7.1%) in the separate G/V group and 4 (8.3%) in the composite G group. The 10-year survival rate including early death was 77% for the whole series, 70% for the separate G/V group and 79% for the composite G group. There was no significant difference in long term survival rate between the separate G/V and composite G groups. No patients required reoperation for the ascending aorta and the aortic valve in the both groups. However, six patients required subsequent operation for aneurysmal disease or dissection of the remaining thoracic and abdominal aorta. The 10-year event free rate of reoperation was 82% for the whole series, 93% for the separate G/V group and 79% for the composite G group. There was no significant difference in the reoperation event free rate between the separate G/V and composite G groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1895598 TI - [Mechanical factors of a severe type of ventricular arrhythmia after Cabrol's operation]. AB - Severe type of ventricular arrhythmia was noticed after Cabrol's operation more frequently than usual reperfusion arrhythmia. Nine patients received Cabrol's operation and 2 of Bentall's were divided into 2 groups according to the occurrence of postsurgical ventricular arrhythmia (Lown's classification grade 0 3: 5 cases, grade 4 A-5: 6 cases), and then the factors contributed to the arrhythmia were analyzed. There were no significant differences between the 2 groups on the point of the characteristics of the cases with or without emergent surgery for, such as ruptured or dissecting thoracic aortic aneurysms or other complicated lesions, the degree of surgical damage, or preoperative cardiac function. The only significant difference between the groups was the angle overheading to the central point of left coronary orifice anastomosed with intermediate tube from the extensive line of the prosthetic flange obtained in the left anterior oblique views on the angiography. The mean value of the angle of the severe group (grade 4 A-5) was 41 +/- 6.8 degrees (mean +/- SD) and significantly acute than the angle of the other group (grade 0-3: 57 +/- 6.4 degrees). This fact suggested that the main reason of the ventricular arrhythmia was coronary ischemia caused by compression of the intermediate tube after formation of massive hematoma within the aneurysmal capsule wrapped over the composite graft. PMID- 1895599 TI - [Interposition graft technique for the treatment of AAE (annuloaortic ectasia) with aortic regurgitation: surgical results]. AB - Interposition graft technique had been used exclusively in 8 consecutive patients with AAE and AR. Two patients with severely dilated left ventricle (CTR 65, 80%, LVDd 93, 83 mm, LVDs 86, 68 mm), and 1 patient complicated with the postoperative mediastinitis died in the perioperative period, 10, 145 and 135 days after surgery, respectively. In the remaining 5 patients, excellent clinical improvement was observed with the reduction of CTR and echo-cardiographic findings without formation of hematoma, pseudoaneurysm, and leak from the suture lines on DSA and CT. PMID- 1895600 TI - [Early and late operative results of simultaneous aortic valve and ascending aorta replacement]. AB - Thirty-four patients of ascending aortic aneurysm associated with aortic regurgitation were treated with simultaneous aortic valve and ascending aorta replacement utilizing composite graft, until December 1990. Twenty-four patients of the group were diagnosed as Marfan's syndrome and 17 had aortic dissection. For the operative procedure, Bentall's technique were employed in 25 patients and other modifications in nine. Operative death was observed in three cases (8.8%) due to low output syndrome, caused by coronary ostium abnormality, all in Marfan's syndrome. Late death was observed in six including 2 hospital deaths of cerebro-vascular disturbance and sepsis. Other causes of death were rupture of residual aneurysm (in 3) and LOS at reoperation (in 1). Hospital survivors remarkably improved in NYHA class and in cardiac size. Actuarial survival in 3, 5, 7, and 10 years were 78%, 72%, 72%, and 62% respectively. Therefore, surgical result of composite graft technique in our institution proved to be reasonable as others. However, long term result of the procedure should be carefully evaluated, because of the anatomical and histopathological peculiarity of the disease. PMID- 1895601 TI - [From Bentall's operation to its modification by Suzuki: improved technique for replacement of both aortic valve and ascending aorta]. AB - To improve the result of surgery for replacement of both aortic valve and ascending aorta, we developed a new technique which is characterized as follows. 1) The composite graft is made during surgery according to the operative findings with tilting disc valve and very low porosity woven Dacron graft. 2) Proximal anastomosis is reinforced by double fixation method. 3) Coronary arteries are reimplanted directly into the graft as a Carrel patch. Thirty-four patients underwent this surgery with no operative death. One died in the hospital and 4 died in the late stage unrelated to the surgical technique. We recommend this method as a new standard technique for replacement of both aortic valve and ascending aorta. PMID- 1895602 TI - [Surgical approach and long-term results on replacement of the aortic valve and ascending aorta with a composite graft]. AB - From March, 1980 to January, 1991, 18 patients, 14 male and 4 female patients ranging in age from 22 to 63 years, were operated on for aortic regurgitation associated with an aneurysm of the ascending aorta. Twelve patients had annuloaortic ectasia; six had DeBakey type I or II dissection; three had Marfan syndrome; and one had aortitis syndrome. The surgical treatment consisted of 16 Bentall operations and 2 modified Cabrol operations with a composite graft and aortic wrapping. The operative mortality was 5.6% (one death). The late mortality has been 4/15. The actuarial survival rate is 82.6% at 5 years and 72.3% at 7 years. Modified Cabrol technique consists of two short interposed grafts with equine pericardial miniskirts between coronary ostia and composite graft, in which Carbomedics mitral valve (No. 23 or 25) is placed 5-10 mm above the proximal extremity. This technique is a safe and reliable method with no bleeding nor mortality and excellent long-term results. PMID- 1895603 TI - [Simultaneous replacement of the aortic valve and the ascending aorta: its operative procedure, early and late postoperative results: especially for annuloaortic ectasia and dissecting aneurysm of the aorta]. AB - During the past 18 years, from March 1972 to February 1991, 105 patients had replacement of the ascending aorta and aortic valve. Operative techniques used in these patients, early and late postoperative results of these patients were reported. One hundred patients had composite graft replacement, and 76 patients of them were treated by Bentall's technique or its modification. Anastomotic leakages after Bentall's operation were found mostly at the bilateral coronary ostia, and incidence rate of the leakages experienced in the first 22 patients who had one lane coronary-graft anastomosis, reduced statistically significantly in patients who had two lane coronary-graft anastomosis, and also survival rate of these latter patients improved significantly than the former patients. A small caliber graft which was interposed between the coronary ostia and side holes of the composite graft was used for coronary reimplantation (Piehler's technique) in cases in which coronary ostia were not displaced cephalad, or in which dissection involved around the coronary ostial tissue even in annuloaortic ectasia. Also CABG was employed in a small number of patients. In the early postoperative results, overall operative mortality was 9.5%. In the long-term results for patients received composite graft replacement until 1989, the actuarial survival rate at 5, 10 and 14 years after surgery was 77, 66 and 60%, respectively. The actuarial survival rate for patients received composite graft replacement with two lane coronary anastomosis at 5 and 10 years after surgery was 82 and 76.2%, respectively, and this results were almost similar to the survival rate after AVR. PMID- 1895605 TI - [Successful report of total aortic root replacement by a new technique]. AB - We employed a new procedure of the total aortic replacement in 2 cases which is made of composite graft and reimplantation of the coronary arteries by direct suture technique. These patients took good clinical course and were discharged after operation. We believe that this procedure is a very useful for annuloaortic ectasia or dissecting aortic aneurysm involved coronary artery with aortic regurgitation. PMID- 1895604 TI - [The surgical treatment of aortic regurgitation with aneurysm of the ascending aorta]. AB - The surgical treatment of the aortic regurgitation with aneurysm of ascending aorta has been considered by Wheat, Bentall and Cabrol as improved combined techniques. 24 cases of the aortic regurgitation with aneurysm of ascending aorta that had been operated in Mitsui Memorial Hospital from November 1975 to August 1990 were examined their late results with the classification of 3 types of operative techniques (aortic valve replacement alone, Bentall's procedure, and Cabrol's procedure). 5 cases of them with aortic valve replacement alone were elected by their aortic angiographic findings, were not significant differences in their late results in the other cases with Bentall's or Cabrol's procedures. So we considered that treatment of the ascending aortic aneurysm with aortic regurgitation would not be necessary to operate with the combined techniques, but their selection of the indication would be limited in the cases that were not widened in aortic ring diameter in their preoperative angiography, and not complicated the systemic diseases such as Marfan's syndrome. PMID- 1895606 TI - [Surgical treatment of ascending aortic lesions associated with aortic insufficiency]. AB - Twenty four patients underwent surgical treatment for ascending aortic lesions with aortic insufficiency at our institution. There were 16 male and 8 female patients from 12 to 67 years. Of 24 patients, 11 patients had Marfan's syndrome, and were younger at the time of operation. Three types of operative procedure were performed, that is, aortic valve replacement (AVR) and supracoronary graft replacement in 4 patients, AVR and covering the aneurysm of ascending aorta in 9, and composite graft replacement of the aortic valve and ascending aorta in 11. One patient died of perioperative myocardial infarction within 30 days after operation (early mortality rate, 4.2%). Another 5 patients died during the initial hospitalization, but no deaths were related to operative procedures. There was a total of 5 (27.8%) late deaths among the 18 patients follow-up with 5 and 10 years survival rate, 60.8%, 52.1%, respectively. Four of five patients was the cases with Marfan's syndrome. There were no statistically significant differences among three different procedures, but all patients who underwent composite graft replacement and left the hospital alive are doing well. PMID- 1895607 TI - [A case of acute dissecting aneurysm associated with AAE (annuloaortic ectasia) necessitating coronary bypass surgery]. AB - We report a successful surgical treatment of acute dissecting aneurysm of the ascending aorta associated with annuloaortic ectasia. The patient was a 29-year old male, who was admitted to the hospital 5 hours after the onset of anterior chest pain. Aortography revealed acute dissection of the ascending aorta (DeBakery type I) with AAE. The intimal tear surrounding the right coronary ostium was found. The procedure between the right coronary artery and aorta (replaced artificial graft) using saphenous vein graft was also required in addition to Bentall's operation. Postoperative studies revealed disappearance of the dissection, patency of the bypass graft. The postoperative course was uneventful and the patient is in active life two years after operation. PMID- 1895608 TI - [A technique for distal anastomosis in replacement of the ascending aorta and aortic valve with a composite graft: application of an open aortic anastomosis under retrograde cerebral perfusion and deep hypothermic systemic circulatory arrest]. AB - Between 1987 to 1990, six patients underwent replacement of the ascending aorta and aortic valve with a composite graft which was not wrapped with aneurysmal aortic wall; annuloaortic ectasia in 4, aortitis with acute onset of aortic regurgitation in 1, and acute aortic dissection with aortic regurgitation in 1. In 2 patients, "open aortic anastomosis" under deep hypothermic systemic circulatory arrest and retrograde cerebral perfusion was utilized for distal anastomosis of the graft to the resected aortic arch. Three patients required no transfusion. One patient with annuloaortic ectasia and severely dilated left ventricle died from ventricular fibrillation in ICU. One patient with aortitis died from stroke due to occlusion of bilateral carotid arteries 3 years postoperatively. The other 4 patients are alive and favorable. It is our belief that this technique still maintains simplicity and facilitates the secured anastomosis and minimized bleeding. PMID- 1895609 TI - [Long-term follow-up results on Bentall's and our modified procedure]. AB - Replacement of the ascending aorta and the aortic valve with composite graft, including reimplantation of coronary ostia, were performed in 84 patients from October, 1978 to December, 1989. Annuloaortic ectasia was the most common indication for surgery (76 patients). Thirty patients (36%) had the Marfan syndrome. Thirty-five patients were performed with original Bentall's procedure. Thirty patients were carried out with our modified technique like Inberg's, the coronary arteries were excised with attachment of the selected piece of the aortic wall, and implanted to the tube prosthesis with continuous suture. Nineteen patients were operated with modified technique by Cabrol or other interposition graft method. The actuarial free of death related to the operation of 4 years was 83%, 88%, and 74% (p = NS) in each methods respectively. The complications of anastomosis, for example, leakage and dilatation of coronary ostia were not seen in our modified Bentall's procedure. In conclusion, our modified method is proved to be reliable and competent. PMID- 1895610 TI - [The Bentall operation for annuloaortic ectasia]. AB - Surgical technique of Bentall operation for annuloaortic ectasia was described with a special emphasis on the technical revisions obtained from the author's own experiences. Most important aspect described in this paper is a complete wrapping of the composite graft with the aneurysmal sac so that the blood leaking from the composite graft is confined within the aneurysmal sac until the blood coagulability is restored. Another emphasis was placed on the suture technique at the site of the right and left coronary ostia anastomosed to the side holes of the composite graft. Intra- and postoperative complications specific for this procedure were also described with their treatment. PMID- 1895611 TI - [Long-term results of operation in patients with annuloaortic ectasia]. AB - From 1974 to 1990, 24 patients were operated on for annuloaortic ectasia. We chose Bentall's technique for 17 patients with great displacement of coronary ostium, but Cabrol's one for 6 patients since coronary displacement was not great. The hospital mortality was 8.3% (2 deaths). The late mortality has been 5/22 (22.7%). Nevertheless, all the patients employed Cabrol's technique have been free from death, events and reoperation. These results were remarkably better than those of primary isolated AVR. It is considered that poor results were caused not by the operating mode using a composite graft but by the connective tissue disorder as primary pathology of annuloaortic ectasia. We conclude that the patient with annuloaortic ectasia must be observed for a long term after operation. PMID- 1895612 TI - [Long-term results with total replacement of the ascending aorta and aortic valve]. AB - From 1971 to 1991, 14 patients, 9 male and 5 female patients ranging in age from 25 to 68 years, were operated on for aortic regurgitation associated with an aneurysm of the ascending aorta. The surgical treatment consisted of 6 cases of Wheat operation, 4 cases of Bentall operation, and 7 cases of Cabrol operation. In 7 cases of Cabrol operation, 3 were reoperations following Wheat or Bentall operations. The operative mortality for the entire group was 28% (4 deaths). The operative mortalities for 6 Wheat operations, 4 Bentall operations, and 7 Cabrol operations were 16%, 75%, and 14%, respectively. Ten patients have been followed from 1 month to 20 years (average 9 years). The late mortality has been 4/10. The cumulative survival rate is 63% at 5 years, 52% at 10 years and 19% at 20 years. Cabrol technique for the treatment of annuloaortic ectasia is an alternative method with relatively low mortality and good-term results. PMID- 1895614 TI - [Aortic replacement with composite or separate valve grafts: early and late results]. AB - From 1974 to March 1991, 34 patients were operated on for ascending aortic aneurysm with aortic regurgitation caused by annuloaortic ectasia (18), dissecting aneurysm (11) and so on. Twenty-one patients underwent composite valve graft replacement, 7 separate valve graft replacement, 5 aortic resuspension and graft replacement, and one aortorrhaphy and aortic valve replacement. Four of these patients required ascending aorta and arch reconstruction. Another two patients who had previous separate valve graft replacement for annulaortic ectasia and required reoperation underwent Bentall operation successfully. The 30 day survival rate was 94%. Recently, we adopted open-unwrapping and aortic button technique. As a result we achieved no homologous blood transfusion by using "Cell Saver" and autologous blood preoperative storage program in four out of five patients of Bentall operation. Late survival rate including operative death were 78% and 63% at 5 and 10 years after operation, respectively. PMID- 1895613 TI - [Replacement of the ascending aorta and aortic valve with a composite graft using a reversed St. Jude medical mitral valve prosthesis]. AB - Between 1981 and 1989, ten patients underwent replacement of the ascending aorta and aortic valve by a composite graft for an aneurysm of the ascending aorta with aortic regurgitation. The first two cases using an SJM aortic valve prosthesis and Teflon felt-pledgeted mattress sutures for the proximal anastomoses required a coronary bypass graft from the tube graft to the anterior descending coronary artery because of difficulty in completing the graft-left coronary ostial anastomoses. In the subsequent seven cases, an SJM mitral valve prosthesis with a large, soft cuff for a valved conduit was sewn in reverse and a thin wall Teflon roll was used for the Teflon felt of the pledgeted mattress suture in the proximal anastomoses. As a result, anastomoses between the tube graft and coronary ostia were performed easily and successfully in eight patients. One case with Marfan syndrome required reoperation nine years after the first operation for recurrence of the aneurysm of the aortic arch. Thus, the need for careful and continued follow-up is important in the Marfan syndrome. PMID- 1895615 TI - [Extracorporeal shock wave lithotripsy and biological effects of underwater shock waves]. AB - The recent development in the treatment of the urinary stones has much to do with underwater shock waves. And urologists have become more aggressive in using this modality in the treatment of the complicated stone patient. However, controversy persists regarding the extent to which the applied voltage and shock wave number interact to induce both cellular injury and stone fragmentation and also the appropriate timing of repeat lithotripsy treatments. It is very short time since underwater shock wave has been initially applied to human body. The effects of the shock wave on the microstructure of the tissues are poorly understood. The questions, what happens at the F2 focus and what happens to the energy after arriving at the F2, remain unclear. The bioeffects of ESWL should be more and more scrutinized. PMID- 1895616 TI - [Establishment and characterization of a cis-diamminedichloro platinum-resistant human bladder cancer cell line]. AB - A cis-diamminedichloroplatinum (CDDP)-resistant cell line, CL-7/CDDP, has been established by chronic exposure of a parent human bladder cancer cell line, T24 (CL-7), to CDDP at progressively increased concentrations for 20 months. CL 7/CDDP was 2.7-fold more resistant to CDDP than CL-7 as determined by colony formation assay. Biological and biochemical characteristics were examined in CL 7/CDDP to compare with CL-7. There were no differences in doubling time and plating efficiency between the two cell lines, but a small one in the mode of chromosome numbers. Intra-cellular CDDP amounts after CDDP exposure showed no difference between the two cell lines, but CL-7/CDDP showed a higher glutathione (GSH) and metallothionein (MT) level. It is suggested that the mechanism of acquired resistance to CDDP is attributed to intra-cellular detoxication, but not to the efflux. CL-7/CDDP may be useful for elucidation of the mechanism of CDDP resistance in human bladder cancer. PMID- 1895617 TI - [Treatment of renal cell carcinoma with human lymphoblastoid interferon alpha and UFT in combination. A prospective multicenter trial]. AB - A cooperative study of combination of UFT (a compound of FT and Uracil) and human lymphoblastoid interferon (IFN-alpha) was conducted in the cases of metastatic renal cell cancer. IFN-alpha was administered over 3 times a week at a dose of 3 X 10(6) units in combination with UFT at a daily dose of 600 mg FT equivalent. Twenty-eight patients from 16 collaborating institutions were the subjects of the present study. The antitumor effects of the drugs were clinically evaluable in 25 cases according to the response criteria of Japan Society for Cancer Therapy. Complete responses and partial responses were observed in 3 and 2 cases, respectively, showing a response rate of 20 per cent. One complete responder had bone and liver metastases and has been alive for more than 2 years without any evidence of relapse. All of the other responders had lung metastasis. The survival durations of the other two complete responders were 716 days and 255 days. The two partial responders had been alive for more than 819 days and 471 days. The adverse effects of this combination therapy were minimal. Combination of a biological response modifier and a cancer chemotherapeutic agent seems to be a way to increase the treatment efficacy of renal cell cancer. PMID- 1895618 TI - [Effects of cyclosporin A on male reproduction in rats]. AB - Effects of cyclosporin (Cs) on male reproduction in rats were examined. A dose dependent decrease of the sperm counts in the cauda epididymis was observed 6 weeks after Cs was administered. A significant decrease of sperm motility was also observed in the each Cs-treated group in any observational period after Cs injection, which suggested an injury to epididymis by Cs. A slight damage of the seminiferous tubules was demonstrated 6 weeks after administration of 40 or 60 mg/kg of Cs. No change in serum levels of luteinizing hormone and testosterone was demonstrated throughout the experiment. But serum levels of follicle stimulating hormone were significant high in any observational period except 6 weeks after Cs injection. It was concluded that Cs gave injuries to both spermatogonia and epididymal function in rat. PMID- 1895619 TI - [Transurethral ultrasonography for the preoperative staging of prostatic cancer]. AB - Transurethral ultrasonography was used to demonstrate the local extension of prostatic cancer in 18 patients undergoing radical prostatectomy. By ultrasonography, capsular penetration of the carcinoma was judged from irregularity and protrusion of the capsule. Infiltration to the seminal vesicle was determined by asymmetry on the echogram. The ultrasound staging was compared to the pathological findings of the step sectioned specimens obtained by total prostatectomy. The accuracy of transurethral ultrasonography in demonstrating the local extension was 94%. The accuracy rates in detecting capsular penetration and depicting seminal vesicle infiltration were 94% and 72%, respectively. The local extension of prostatic cancer has been evaluated by transrectal and transabdominal scannings. Ultrasonography is considered to be more reliable than digital rectal examination, CT or MRI in the preoperative staging of the prostatic cancer. The present study revealed that transurethral ultrasonography had advantage in demonstrating the capsule of the prostate for the following reasons; 1) there is no interposing tissue between the probe and prostate because the probe is inserted into the prostatic urethra, 2) the prostate is observed without deformity caused by the balloon in the rectum, and 3) the beam hits the capsule perpendicularly. The prostatic cancer at the portion of capsular penetration was hypoechoic or anechoic pathologically, these areas corresponded to homogeneous and large cancer nodules. Transurethral ultrasonography is valuable in demonstrating local extension of the prostatic cancer, in particular capsular penetration. PMID- 1895620 TI - [Vesicourethral dysfunction of diabetic patients]. AB - In order to evaluate vesicourethral dysfunction in diabetic patients, urodynamic studies, IVP and urinalysis were performed on 173 diabetic patients (male 78, female 95) and 17 nondiabetic control cases. In addition to the classical findings as increased volume at the first desire to void and decreased maximum vesical pressure, diabetic patients showed varieties of vesicourethral dysfunctions such as overactive bladder (14.5%), low compliance bladder (11.0%) and loss of detrusor-external sphincter coordination (31.7%). Vesicourethral function of diabetics was classified in following 5 types by analysing the volume at first desire to void, volume at maximum desire to void, maximum vesical pressure, residual urine volume and bladder compliance. 1. Type 1, normal vesical function, 13 cases. 2. Type 2, vesical dysfunction with minimal residual urine, 49 cases. 3. Type 3, vesical dysfunction with residual urine, 66 cases. 4. Type 4, low compliance bladder, 20 cases. 5. Type 5, overactive bladder, 25 cases. Pyuria was observed in 59.8%, hydronephrosis was found in 10.9% and ectasia of lower ureter was found in 17.8% of diabetic patients. The highest incidence of pyuria and abnormality of the upper urinary tract were noted in Type 4 and followed by Type 3 and by Type 2 in decreasing order. Extent of pyuria and ectasis of the upper urinary tract showed statistically significant correlation with residual urine volume and detrusor-external sphincter coordination. When vesicourethral function was compensated by abdominal strain, the volume of residual urine is not elevated, but when the mechanism of compensation is lost or in the absence of detrusor-external sphincter coordination results in gradual accumulation of residual urine. In cases with long standing chronic urinary tract infection may results in fibrosis of the bladder wall with low compliance bladder. Fibrotic obstruction of uretero-vesical junction can cause hydroureteronephrosis and followed by renal function impairment. As vesical damage become irreversible at this end stage, proper management during early stage is crucial for management of diabetic patients. Cholinergic agent were effective to reduce residual urine volume in Type 3. alpha-blocking agent were effective to reduce residual urine volume in Type 3 and some cases of Type 4. In cases in which medication therapy failed to reduce residual urine, the clean intermittent catheterization was successful in control of urinary tract infection and upper urinary tract ectasis. Transurethral resection of the prostate and the bladder neck is indicated in the male patients with a large amount of residual urine in Type 3 and 4. PMID- 1895621 TI - [Studies on detection of serum IgA and IgG antibodies specific for Chlamydia trachomatis in latent infections in males]. AB - We determined the serum concentrations of IgA and IgG antibodies specific for Chlamydia trachomatis (C. trachomatis) by an indirect immunoperoxidase assay (IPAzyme kit, Savyon Diagnostics, Ltd., Bee, Shova, Israel) to evaluate their diagnostic significance in latent infections in males. Forty-five asymptomatic males whose wife or partner was suspected to be infected with C. trachomatis were studied and the incidence of serum IgA (titer greater than or equal to 16) and IgG (titer greater than or equal to 64) antibodies for C. trachomatis was compared with that in a healthy group, a group with non-gonococcal urethritis (NGU) patients. Changes in IgA titer during treatment were also examined. The incidence of IgA and IgG antibodies in the healthy group was found to be 2.4% and 11.9% in males, and 4.8% and 18.1% in females, respectively. In patients whose wife or partner who was positive to C. trachomatis, the incidence of IgA and IgG antibodies was 42.2% and 75.6%, respectively. In the NGU patients the incidence of IgA and IgG antibodies was 56.3% and 62.5%, respectively. The incidence of IgA and IgG antibodies in patients whose wife or partner was antibody-positive were significantly higher (p less than 0.01) than the corresponding value in healthy men and women, but there was no significant difference from NGU patients or the elderly group. The IgA antibody titer during treatment of C. trachomatis infection showed no reduction in some cases. This study revealed frequent latent incidence of C. trachomatis infection in male patients. Determination of C. trachomatis IgA and IgG antibodies is considered to be supplemental for diagnosis of chlamydial latent infections. PMID- 1895622 TI - [Sexual disturbance caused by endocrine dysfunction]. AB - Nineteen cases of sexual disturbance caused by endocrine dysfunction were surveyed for the clinical features. In hypogonadotropic hypogonadism ejaculatory failure was observed in 12 out of 13 cases. On the contrary, 2 of three hypergonadotropic patients preserved their ejaculation. The serum testosterone levels of hypogonadotropic and hypergonadotropic hypogonadism were less than 200 ng/dl. When the testosterone level decreased to less than 100 ng/dl, nine patients out of 13 complained loss of libido and 12 patients complained loss of ejaculation, but six patients preserved erectile function. Hyperprolactinemic patients showed loss of libido in 4, erectile failure in 4 and loss of ejaculation in 2. When good response to hCG test was present or the testicular volume was more than 4 ml, patients with hypogonadotropic hypogonadism showed good response to hCG therapy. PMID- 1895623 TI - [Posterior urethral valves. Experience with 21 cases]. AB - Twenty-one cases of posterior urethral valves experienced in the last 26 years were reported with special references to the morphological and functional sequelae of the upper and lower urinary tracts after the valve ablation. Furthermore, several problems, such as transient urinary diversion, vesicoureteral reflux (VUR), lower ureteral obstruction, transurethral valve ablation, bladder function and renal insufficiency, were also discussed. The age at the first examination ranged from 0 day to 13 years. Eight boys were first examined under one year of age. Although the most frequent complaint was urinary infection, some characteristic features were observed in each age group. In all of the children the valves were classified as type I (Young). Seven children had severe ones. Endoscopic examination was thought to be essential to find mild ones. VUR was found in 16 children (28 ureters). Grade IV was encountered most frequently (13 ureters) with prominent laterality to the left side. The severity of the renal scar paralleled to the grade of VUR. Most of the dwarf kidneys were thought to be hypodysplastic. Valve ablation was performed immediately after the diagnosis in 17 of the 21 children. Eight children were under one year of age when their valves were ablated. As a principle, VUR was followed conservatively after the valve ablation. VUR highly tended to disappear or improve when it was of low grade or valve ablation was performed under one year of age. However, when the ureteral orifices were disappearance of VUR was rare and recovery of renal function was not observed. In 5 children antireflux surgery was added. Although a dilated upper urinary tract without VUR was found in 2 children (2 ureters), it disappeared promptly after the valve ablation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1895624 TI - [Initial experience using a new type extracorporeal lithotripter with an anti miss-shot control device]. AB - The results of clinical trial using a TOSHIBA piezolectric extracorporeal lithotripter are presented. The advantages of this machine are the installation of an anti-miss-shot control device (AMCD) to prevent miss-shots to the renal tissue and the improved ultrasound stone localization by an over-head type applicator. AMCD functions so that shock waves are generated only when the stone is in the focal region. Forty patients with urinary tract stone were treated by this machine from October 1989 to March 1990 at the Department of Urology, Tohoku University School of Medicine. Almost all patients could be treated with an analgesic only. The X-ray film obtained three months after ESWL treatment showed that 23 cases (57.5%) were stone-free and 10 cases (25.0%) had stone fragments of less than 4 mm. The successful rate of ESWL using this machine was 82.5%, the result was better than that using other piezolectric machines. No serious complication was observed, except mild hematuria in all cases. Milder postoperative hematuria suggested the decrease of renal tissue injury. It is concluded that the treatment with this machine is safe and seems to be more favorable than the conventional ones. PMID- 1895626 TI - [Clinical analysis of patients with occupational urothelial tumors]. AB - The incidence of occupational urothelial tumor and the accompanied problems were studied on the workers who had manufactured or handled aromatic amines at a certain chemical factory. Twenty-five out of 398 dyestuff workers, who were examined at regular intervals, were found to have urothelial tumors and the incidence rate was 63%. The mean age at onset, the mean period of aromatic exposure and the mean latent period from the initial exposure until tumor development were 61 year-old, 7.2 years and 30 years, respectively. A high incidence rate was found in the long exposed workers and the smoking group. The negative correlation was observed between the age of first exposure to carcinogens and the latent period. The workers who had been exposed to two or three kinds of aromatic amines had the highest incidence followed by those exposed to benzidine and those to alpha-naphthylamine. No urothelial tumor occurred in the workers exposed to beta-naphthylamine. Ninety-four percent of the initial tumors were superficial and transurethral resection of tumors was performed as the initial surgery for the patients with bladder tumors. The recurrence rate in the bladder cavity after the surgery was 39%, which was almost the same rate as that of non-occupational bladder tumors, however, the recurrence rate in the upper urinary tract was high (26%). The positive rate in the examination of urine cytology was 60% for initial tumors, 74% for recurrent tumors. The urine cytology was a significant method for the detection and monitoring of the patients with occupational urothelial tumors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1895625 TI - [Renal carcinoma in hemodialysis patients. Specially concerned with acquired cyst]. AB - Acquired cystic disease of the kidney (ACDK) with carcinoma in the original kidney is one sensational complication of long-term hemodialysis patients. The rate of incidence is about forty times higher than that in the general population and especially high in the young male group. From Dec. 1978 to Nov. 1990, we identified 8 patients of ACDK by computerized tomography (CT) scan, sonographic examination and angiography. Most patients had no clinical symptoms. The mean term of hemodialysis of the patients was 8 yrs. And one patient was diagnosed as having ACDK and tumor 8 yrs after kidney transplantation and then the kidney was removed. Their mean age was about 32 y.o. and the tumor size 1-3 cm in diameter. All tumors were inside the renal capsule. (Robson-1) Pathohistologically, the tumor area consisted of mainly clear cell carcinoma and the epithelium of the cyst wall showed multi-layered or papillary hyperplasia. In the 1st and 7th cases, simple nephrectomy was performed by transperitoneal approach. In the other cases it was performed by flank incision. All cases have had no recurrence and no metastasis of renal carcinoma. The etiology of ACDK and carcinoma occurrence has not been clarified yet, but it is suggested that uremic metabolite and deficiency of immuno-surveillance may cause the pathological changes in kidney tissue. PMID- 1895627 TI - [Experimental and clinical studies of urethral anesthesia on etiology and treatment of detrusor-sphincter dyssynergia]. AB - We studied whether detrusor-sphincter synergia during micturition was obtained by means of urethral anesthesia with lidocaine hydrochloride in five thoracic spinal cats and eight clinical cases with detrusor-sphincter dyssynergia. In thoracic spinal cats with detrusor-sphincter dyssynergia, urethral anesthesia produced detrusor-sphincter synergia, an increase in the maximum bladder pressure and a decrease in the residual volume. In clinical cases with detrusor-sphincter dyssynergia, urethral anesthesia produced detrusor-sphincter synergia or a decrease in the external urethral sphincter activities during micturition, and a decrease in the maximum urethral closure pressure and the residual volume. There were no remarkable changes of the external urethral sphincter activities during urine storage phase before and after urethral anesthesia in both spinal cats and clinical cases. These results suggest that urethral anesthesia blocks the urethro urethral contraction reflex and secondarily activates vesico-urethral relaxation reflex. The block of urethral sensory nerves is thought to effectively treat detrusor-sphincter dyssynergia. PMID- 1895628 TI - [Angiographic analysis of intratumoral Pt concentration on intra-arterial infusion therapy for bladder cancer]. AB - Eleven patients with advanced bladder cancers (T2-4) were treated by intra arterial CDDP infusion therapy and intratumoral Pt concentrations were measured. The following results and suggestions were obtained by comparing the histological effects and intratumoral Pt conc. 1) By calculating cross section areas from diameter of blood vessels, the blood flow distributions of tumor feeding arteries were estimated. Based on this distributions, the distributed CDDP dosage flowed into the tumor feeding arteries was calculated. The distributed CDDP dosage of histologically effective group (N = 5, Grade IIb less than by Shimosato histological evaluation) were significantly higher than that of ineffective group (N = 6, Grade IIa greater than). (p less than 0.02, Student t test). 2) A good correlation was obtained between the revised intratumoral Pt value by distributed CDDP dosages and intervals from intra-arterial infusion therapies to operations. (r = -0.90, p less than 0.001). Intratumoral Pt conc. declined with a half life of 12 weeks. 3) Based on the declined linear line calculated from 2), theoretical intratumoral Pt conc. which was presumed value on day 0 (just after intra arterial infusion therapy) were calculated. Theoretical Pt conc. of effective group were significantly higher than that of ineffective group (p less than 0.01), although no significant difference was seen between two groups compared by net intratumoral Pt conc. 4) A good correlation was seen between theoretical intratumoral Pt conc. and distributed CDDP dosage (r = 0.89, p less than 0.01). 5) Five of 6 cases with above 5 micrograms/g of theoretical intratumoral Pt conc. were histologically effective, and 5 micrograms/g of theoretical Pt conc. corresponded to 31 mg of distributed CDDP dosage.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1895629 TI - [Primary carcinoid tumor of the testis with metastasis to the upper vertebrae. Report of a case]. AB - A case of primary carcinoid tumor of the right testis with metastases to the cervical and thoracic vertebrae and epidural is reported. A 53-year-old man was first recognized as being with dysthesia of the left arm and shoulder in April 1986. In June, 1987, he was admitted to the Neurology service, complaining of sudden occurrence of abasia. Myelography and computerized tomography demonstrated an epidural mass and several high density areas in the vertebral bodies of Th1 and Th2. The patient underwent laminectomy from C7 to Th2. At operation, the neurosurgeons noticed a tumor mass in the right scrotum and requested our consultation. Thus right high orchiectomy was performed. Pathological examination including Grimerius' and Fontana-Masson's stain revealed carcinoid tumor of the right testis associated with metastases to the spinal column. Postoperatively, tumor maker studies revealed elevation of blood 5-hydroxytryptophan and marked increase of urinary 5-hydroxy-indoleacetic acid excretion. They showed remarkable decreases after a course of PVB chemotherapy. The patient has been under our observation as an out-patient for the past 27 months with metastases. This is the first case of primary carcinoid tumor of the testis with metastases so far reported in the domestic literature. PMID- 1895630 TI - [Bladder involvement in HTLV-I associated myelopathy]. AB - The HTLV-I infection was endemic in south western Kyushu. This human T lymphotropic virus type I may cause HTLV-I associated myelopathy (HAM), a neurological disease characterized by a spastic paraparesis. And one of the minor diagnostic features of HAM is the presence of cystorectal disturbance. We experienced 35 HAM patients with a neurogenic bladder. A gradually progressive contracted bladder was observed in 3 of them. The main pathological finding in these patients was submucosal infiltration of lymphocytes. These findings suggest that immunologic mechanisms account for the development of bladder lesions. PMID- 1895631 TI - Adolescent babysitters face a formidable task. PMID- 1895632 TI - BAN "A" FALL: a nursing innovation to reducing patient falls. PMID- 1895633 TI - Music's affect on stress-related responses during surgery. PMID- 1895634 TI - [A case of development of "exit blockade" and spontaneous increase of the refractory period in a patient with implanted pacemaker]. PMID- 1895635 TI - [Hemodynamic changes in patients with ischemic heart disease during conducting exercise and dipyridamole tests and transesophageal electric cardiac pacing]. PMID- 1895636 TI - [Reproducibility of functional classification in patients with stable angina pectoris]. AB - Diagnostic indices based on various sets of signs were developed to define functional classes of angina pectoris. At the same simultaneous application of clinical parameters (age, conditions for onset of anginal episodes and their arrest, the number of weekly anginal episodes, the level of daily exercise, over 1-mm ST segment depression, resting ECG signs of left ventricular hypertrophy, etc.) and bicycle ergometer testing data (cardiac output, peak exercise heart rate, etc.) augmented the accuracy and reliability of identification of a functional class in patients with stable angina. The diagnostic indices are highly reproducible and may be useful in the assessment of the course of the disease and its prognosis in patients with coronary heart disease. PMID- 1895637 TI - [Study of the effect of the parameters of physical exercise on the dynamics of ischemic reaction in patients with stable stenocardia]. AB - The intensity and duration of exercise were investigated for their influence on the parameters of myocardial ischemia and its severity in 25 patients with Functional Classes II-IV angina who underwent intermittent, stepwise increasing exercises. It was ascertained that there were basic correlations between the intensity and duration of exercise and conventional myocardial ischemic parameters and there were no such correlations for threshold parameters that allowed the coronary reserve and function to be objectively evaluated in patients with angina. The maximal correlation slope angles between heart rate, ST regiment displacement and exercise intensity of various duration were proposed for individual characterization of the specific features of control of the cardiovascular system and severity of myocardial ischemia. PMID- 1895638 TI - [Status of coronary venous blood flow in patients with ischemic heart disease in myocardial ischemia induced by the atrial stimulation test]. AB - A total of 85 patients (68 with coronary heart disease in the presence of effort angina of various functional classes (a major group) and 17 with neurocirculatory++ dystonia and cardialgic syndrome (a control group)) were examined. Heart failure severity and blood flow distribution in the functioning myocardial areas were evaluated in transient ischemia induced by atrial pacing. Three levels of coronary venous blood flow were defined in patients with coronary heart disease. A relationship between the coronary blood flow, disease history duration, and coronary blood flow changes was examined in cardioselective exercise. PMID- 1895639 TI - [Effect of the contractile function of the myocardium on the nature of hemodynamic reactions in patients with ischemic heart disease during Valsalva's test]. AB - Application of contrast cineventriculography and probe of the left ventricle indicated that there was a relationship between the status of myocardial contractility, its function, some hemodynamic parameters, the severity of regional left ventricular wall contractility impairments and the nature of a hemodynamic response to Valsalva's test. Normal left ventricular contractility determined sinusoidal responses. Decompensated impairments of myocardial contractility gave rise to a square wave. A response represented as a nil ++super elevation was caused by a moderate impairment of left ventricular contractility and, probably, by the absence of adequate vasoconstriction in the fourth phase of Valsalva's test. PMID- 1895640 TI - [Early systolic and pansystolic murmurs--the main variants of the papillary muscle dysfunction in patients after myocardial infarction]. AB - Cardiac auscultation, phonocardiography, and two- dimensional echocardiography were performed in 32 patients who had sustained myocardial infarction in the presence of signs of mitral valve malfunction. Incomplete systolic closure of the mitral valve leaflets was detected in all the patients. The pattern of murmur appeared as its pansystolic and early systolic varieties. Apex rhomboid and late systolic murmurs were found in individual patients. The early systolic murmur was less loud and more frequently local than the pansystolic murmur. Twelve of 15 patients with the murmur proved to have an ++un-enlarged left ventricle. It is concluded that the occurrence of systolic murmur in the papillary muscle dysfunction syndrome is attributed to incomplete closure of the mitral++ valve. Left ventricular dilation results in transition of early systolic murmur to its pansystolic variant. PMID- 1895641 TI - [Evaluation of the overall contractile function of the right ventricle using two dimensional echocardiography in patients with myocardial infarction]. AB - The paper presents two methods for calculating the contractile function of the right ventricle (RV): (1) three-plane one with the use of short- and long-axis cut RV; (2) single-plane one which was modified to the use of long-axis RV images in the projection of 4 chambers. A total of 56 patients with first acute gross myocardial infarction were studied. A control group included 14 healthy subjects aged 25-60 years. The proposed three-plane method for estimating the volume parameters and ejection fraction of the right ventricle was shown to correlate with contrast ventriculography significantly. A high correlation was found between the stroke output of RV (as calculated for the left ventricle by the Chapman method) and that (by the three-plane method). The RV volume values in patients with anterior or inferior myocardial infarction suggest that there is a trend to suppress RV function in the patients, but it is more specific for those with inferior myocardial infarction. PMID- 1895642 TI - [Knowledge of health problems among male non-autochthonous population of Chukotka]. AB - In the random sample of 762 males aged 30-59 years who had moved to Chukotka, the attitude towards their health, a physician, bad habits, and prevention of diseases was examined within the Programme on Epidemiology of Major Non Communicable Diseases and Their Risk Factors among the residents of the Chukotsky Autonomous District. The non-aboriginal Chukotka's population having higher risk factors showed decreased self-appraisal of their health, inadequate awareness of their health and risk factors for diseases. However, the majority of the male population consider it useful to be surveyed, which should be borne in mind in implementing educational measures among these population groups. PMID- 1895643 TI - [ECG U wave phases in patients with ischemic heart disease and diabetes mellitus]. PMID- 1895644 TI - [Arrhythmia in patients after heart transplantation]. AB - Holter monitoring was performed in 15 patients surviving over 3 months after homotopic cardiac transplantation. The frequency and types of arrhythmias occurring in the grafted innervated heart were studied according to its postoperative period duration. The follow-up lasted 3 to 29 months. Supraventricular arrhythmias were detected in 80%, whereas ventricular ones were found in 86.7%. Ventricular arrhythmias accompanied chronic graft rejection in 2 patients. It was ascertained that Holter monitoring was of greater diagnostic value than routine ECG recording. Innervation is not essential in the occurrence of cardiac arrhythmias. PMID- 1895646 TI - [Disorders of heart conduction after short-term hyperthermia of the body]. PMID- 1895645 TI - [Effect of ritmilen on myocardial refractility and cardiac impulse conduction in patients with paroxysmal tachycardia]. AB - By choosing antiarrhythmic therapy, ritmilen, 3 mg/kg, was given to 30 patients with atrial, atrioventricular, reciprocal and ventricular tachycardias. The agent was found to have the highest effect on atrial myocardial refractoriness in patients with atrial tachycardias and on ventricular refractoriness in patients with ventricular tachycardias (longer effective and functional refractory periods). Intraventricular pathways are the major site of ritmilen's effect on anterograde conduction. Profound changes were found in patients with atrial and ventricular tachycardias. The cholinolytic action of ritmilen on the atrioventricular node was detected in 20% of the patients, whereas sinus rhythm increased in 90%, which may be attributable to asymmetric vagus innervation of sinoatrial and atrioventricular nodes. PMID- 1895647 TI - [Prospects for the development of the studies regarding the prevention of cardiovascular diseases]. PMID- 1895648 TI - [Functional state of the left regions of the heart in healthy persons during isometric exercise]. AB - Hemodynamic parameters of left and atrial contractile and pump functions were examined in 25 healthy males undergoing leg isometric exercise, by employing echocardiography. Analysis of changes in intracardiac hemodynamics showed that for provision of a marked pressor reaction occurring in healthy persons during isometric exercise, there was enhanced left ventricular myocardial contractility and thereby higher stroke and minute volumes. To maintain the required increase in stroke volume at the maximal exercise level, an accessory mechanism of compensation gears (by the Frank-Starling type), which operates due to myocardial diastolic relaxation, elevated venous blood supply at the expense of sucking cardiac action, and augmented left atrial contractility. PMID- 1895649 TI - [Physical exertion tolerance and its determining factors in hypertrophic cardiomyopathy]. AB - A contribution of specific features of myocardial hypertrophy and hypercontractility left ventricular diastolic dysfunction to decreased exercise tolerance and developed coronary failure is discussed on the basis of results obtained from a bicycle ergometric test performed in 40 patients with hypertrophic cardiomyopathy. Thallium-201 myocardial scintigraphy conducted at the maximum exercise in 17 patients revealed a reduction in coronary reserve with increased myocardial mass index that was higher than the critical value. An implication of severe myocardial hypertrophy in the presence with coexisting left ventricular posterior wall hypertrophy and impaired perfusion/mass ratios is considered as a risk factor for death of patients with hypertrophic cardiomyopathy. PMID- 1895650 TI - [Functional interrelations between the thermo-topographic indicators in healthy persons with hemodynamic status of the body]. AB - ++Thermo-topography was studied by decimeter radiothermometry on a DPT-30 apparatus which determined the integral ++sub-superficial temperature of a tissue layer at a depth of 3-5 cm. Thermal probing was performed at point 41 onto the dorsal and ventral surfaces of the human body. Hemodynamics was explored by tetrapolar thoracic rheography. A total of 83 young healthy males were studied. Associated changes in temperatures and hemodynamic parameters were established. The radioluminance thermal profile of patients with tachycardia was significantly altered as compared to those with bradycardia. The ++sub-superficial temperatures in the proximal regions of the body rose by 0.3-0.7 degree C. The feet in subjects with rapid pulse were colder, which led to significantly higher values of distal and proximal lower extremity, temperature gradients. In persons with hyperkinetic circulation, the temperatures in the ++cranio-corporeal regions were significantly greater by 0.2-0.6 degree C than those in subjects with eu- and hypokinetic circulations. PMID- 1895651 TI - [Detection and quantitative evaluation of functional disorders of the tricuspid valve during conducting of the treadmill test in patients with mitral valve defects]. AB - A multi-stage treadmill test was performed in 80 patients with mitral valvular disease and 24 healthy subjects. In organic involvement of the tricuspid valve, there was a decrease in oxygen uptake increase to 0.36 metabolic units at Stage 3 of the proposed treadmill test protocol versus 1.02 units (p less than 0.05) in patients without this valve disease or healthy individuals. The sensitivity and specificity of the oxygen uptake stabilization as a diagnostic sign accounted for 75% and 91%, respectively. The stabilization was demonstrated to reflect pulmonary effective oxygenized blood flow derangement. It is concluded that the load leading to oxygen uptake stabilization quantitatively shows the severity of hemodynamic tricuspid valve dysfunctions. PMID- 1895652 TI - [Comparison of the symptoms of myocardial functional and metabolic disorders in patients with heart valve diseases]. PMID- 1895653 TI - [Significance of the changes in initial and terminal segments of the ventricular ECG complex for evaluation of the status of myocardial energy metabolism in patients with mitral valve defects with predominant stenosis]. AB - The amplitude-time and velocity parameters of QRS complex and T wave were compared with intraoperative values of aerobic and anaerobic myocardial energy metabolism (as shown by left auricle biopsy) in 187 patients with mitral valve disease with predominant stenosis. The ECG elements were demonstrated to be of informative value for the evaluation of myocardial energy metabolism and the clinical condition of the patients. The ratio of descending T wave downsloping to its ascending upsloping rates, as well as the amplitude-time parameter of QRS complex and T wave were demonstrated to be closely related to myocardial energy metabolism. PMID- 1895654 TI - [Cardiac function after radical correction of tetralogy of Fallot in infants]. AB - A total of 20 patients (mean age 8.9 months) were examined after total correction of Fallot's tetralogy, 9 of them underwent transannular plasty and 11, separate right ventricular outflow tract plasty. Two-dimensional and Doppler echocardiographies were used to measure cardiac index, end-diastolic and end systolic volumes, ejection fraction of the left and right ventricles, regurgitation fraction on the pulmonary and tricuspid valves, right ventricular pulmonary artery pressure gradient. The study of the immediate postoperative period indicated that the pattern of its course was affected by the type of right ventricular outflow tract plasty, however, its function (ejection fraction) remained diminished in the periods up to 12 months of the operation. Pulmonary valve regurgitation was found to be one of the factors contributing to its diminution. PMID- 1895656 TI - [Newly developed stenocardia: effect of intensive physical training on the indicators of the blood coagulation system and fibrinolysis]. AB - The impact of 6-week strenuous exercise training (SET) on blood coagulative and fibrinolytic parameters (levels of fibrinogen, soluble fibrin, fibrinogen-fibrin degradation products, activities of plasminogen and plasmin) was studied in 28 patients with first angina pectoris, in 16 of whom in the first 3 months of onset of the disease, but angina pectoris lasting 3-4 prior to SET. The 6-week strenuous exercises in patients with first angina were found to cause a decrease in fibrinogen levels, exert no action on thrombin and fibrin formation. They did not diminish plasminogen activator release during exercise in patients with pre exercise unstable angina. PMID- 1895655 TI - [Radionuclide ventriculography in the evaluation of myocardial function in patients with chronic nonspecific lung diseases]. PMID- 1895657 TI - [Formation and reversal development of the local mechanisms of heart protection during adaptation to continuous stress]. AB - Experiments with isolated rat hearts demonstrated that in the course of adaptation to continuous immobilized stress of moderate intensity (1, 5, and 15 days), the heart gradually (at day 15) formed the defense mechanism previously described, that is the adaptive structural stabilization phenomenon (ASSP). ASSP defends cardiac contractile function and has a powerful antiarrhythmic and cytoprotective effect in total ischemia, reperfusion, and under the action of toxic concentrations of calcium and catecholamines. The protective ASSP effect formed over 15 days of continuous stress proved to be steady-state, remaining for 15 days of adaptation cessation. Thus, during adaptation to continuous stress higher regulatory mechanisms determine the gradual development of a highly effective defense mechanism in the heart at the cellular level. PMID- 1895658 TI - [The role of the sympathetic-adrenal system in the development of hypertension. Effect of the emotional factor]. PMID- 1895659 TI - [Myocardial infarction with the presence or absence of pathologic Q wave]. PMID- 1895660 TI - [Duration of hospital treatment of patients with myocardial infarction]. PMID- 1895661 TI - [Atrial fibrillation. Restoration of the sinus rhythm in patients with a persistent form of atrial fibrillation]. PMID- 1895662 TI - Basolateral membrane H/HCO3 transport in renal tubules. PMID- 1895663 TI - Differences in vascular reactivity in models of ischemic acute renal failure. AB - To determine the mechanism of observed differences in vasoreactivity in norepinephrine-induced (NE) and renal artery clamp (RAC) models of ischemic acute renal failure (ARF), induction renal blood flow (RBF) was measured and vascular reactivity examined one week thereafter in NE- and RAC-ARF rat kidneys that had identical levels of renal dysfunction. Morphology also was compared at 48 hours and one week. In NE-ARF, RBF was 14% during 90 minutes of induction and by 60 minutes post-NE infusion was only 18% of baseline. In contrast, in RAC-ARF RBF was effectively 0 for 75 minutes but returned to 95% of baseline by 60 minutes after clamp release. At one week there was a paradoxical increase in renovascular resistance (RVR) to renal perfusion pressure (RPP) reduction in the autoregulatory range and an augmented vasoconstriction to renal nerve stimulation (RNS) in NE-ARF, but no change in RVR and minimal reduction in RBF to these same respective stimuli in RAC-ARF (both different at P less than 0.001). NE-ARF were more sensitive to intrarenal norepinephrine than RAC-ARF kidneys (P less than 0.001). Neither NE- nor RAC-ARF kidneys responded to endothelium-dependent acetylcholine (ACh). Vasodilation to endothelium-independent prostacyclin (PGI2) in NE- was similar to sham-ARF, but there was an attenuated response in RAC-ARF kidneys (P less than 0.001). Morphology at 48 hours showed smooth muscle necrosis in half of the resistance vessels in RAC- but in less than 10% of those in NE ARF. Except for a slightly greater frequency of tubular casts at 48 hours in RAC ARF, tubular injury was indistinguishable. It is concluded that NE-ARF has evidence of a predominant functional endothelial vascular injury while RAC-ARF has both morphologic and functional evidence of a predominant smooth muscle injury. Differences in vascular injury between the two models, at least in part, may be the consequence of differences in severity of initial ischemia and/or the rates of recovery of RBF; however, an additional or separate toxic effect of infused NE cannot be excluded. PMID- 1895664 TI - SGP-2 expression as a genetic marker of progressive cellular pathology in experimental hydronephrosis. AB - The onset of hydronephrosis following unilateral ureteral obstruction is associated with the induced expression of RNA and proteins encoded by the SGP-2 gene. SGP-2 expression has been shown to demarcate mammalian cells undergoing apoptosis. Using in situ hybridization, the cellular localization of SGP-2 expression in the obstructed kidney was determined as a means to study the various phases involved in the progression of hydronephrosis. Within 30 minutes of obstruction, SGP-2 mRNA expression was localized to the adventitial layers of the hilar arteries and intrarenal arterioles. Increasing time of obstruction resulted in the notable absence or depletion of this layer. In addition, the pattern of SGP-2 expression changed with time to the collecting ducts and distal tubules. This study identifies the vascular support tissue of the kidney as the initial site of reaction and potential cell death following ureteral obstruction. We believe that this observation may be of importance in explaining the early alterations in blood flow associated with hydronephrosis. PMID- 1895665 TI - Effects of nifedipine and enalapril on glomerular structure and function in uninephrectomized SHR. AB - Spontaneously hypertensive rats (SHR) that underwent uninephrectomy (UNX) at six weeks of age were randomly assigned to receive no treatment, the calcium channel blocker, nifedipine, or the angiotensin converting enzyme inhibitor, enalapril. Both drugs reduced systemic blood pressure, however, blood pressure tended to be greater in rats given nifedipine than in those on enalapril. After six months, proteinuria and the relevance of glomerula sclerosis were significantly reduced in the two treated groups compared to values observed in untreated SHR. Kidney weight was also reduced by therapy, suggesting that both enalapril and nifedipine inhibited compensatory kidney growth. Micropuncture studies performed in similarly treated groups of rats, but at 11 weeks of age, revealed that PGC was elevated in untreated UNX SHR and reduced by both nifedipine and enalapril. These findings support the hypothesis that glomerular hypertension and renal hypertrophy are important risk factors for glomerular injury. They suggest that calcium blockers are as effective as angiotensin converting enzyme inhibitors in preventing progressive kidney damage. PMID- 1895666 TI - Biochemical characterization of contractile proteins of rat cultured mesangial cells. AB - We examined characteristics of contractile proteins of rat cultured mesangial cells. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed that actomyosin was a major protein component in the extract of mesangial cells. By Western blot, tropomyosin, caldesmon, alpha-actinin, and vinculin were recognized in mesangial cells. The molecular masses of alpha-actinin and vinculin were the same as aortic smooth muscle. Mesangial cells contained five tropomyosin isoforms: TM-1, -2, -3, -4, and -5. TM-1 was present as a major isoform in mesangial cells, and it had an immunological cross reactivity with beta tropomyosin of aortic smooth muscle. On the other hand, the molecular mass of caldesmon was similar to dermal fibroblasts, and differed from aortic smooth muscle. Immunofluorescent studies showed that the staining patterns of tropomyosin and caldesmon between cultured mesangial cells and cultured vascular smooth muscle cells were somewhat different. From these results, we conclude that mesangial cells abound in contractile proteins, and that the compositions of these proteins are similar to those of aortic smooth muscle with minor differences. Thus, this study appears to biochemically support a hypothesis that mesangial cells are derived from vascular smooth muscle cells, but with a minor modification in their evolution. PMID- 1895667 TI - Impact of dietary fatty acid supplementation on renal injury in obese Zucker rats. AB - We previously reported that renal injury in hyperlipidemic, obese Zucker rats was associated with a relative deficiency of tissue polyunsaturated fatty acids (PUFA). In the present study 10-week-old obese Zucker rats were pair fed regular chow or chow containing either 20% sunflower oil rich in n-6 PUFA, fish oil rich in n-3 PUFA, coconut oil medium-chain saturated fatty acid, or beef tallow long chain saturated fatty acid. At 34 weeks of age there were comparable reductions in albuminuria, mesangial matrix expansion, and glomerulosclerosis in the fish oil and sunflower oil groups. While both fish oil and sunflower oil reduced serum triglycerides, and improved the composition of triglyceride-enriched lipoproteins, only fish oil decreased serum cholesterol. The effect of the dietary fatty acid supplementation on fatty acid profiles were similar in isolated glomeruli and cortical tissue. In general, the amelioration in injury in the fish oil and sunflower oil fed rats was most closely linked to glomerular levels of PUFA, either n-6 or n-3. These data suggest that hyperlipidemia and abnormalities in tissue FA are closely linked, and that dietary supplementation with PUFA may ameliorate chronic, progressive renal injury. PMID- 1895668 TI - Cortisone effects on growth, food efficiency, and in vitro growth hormone release. AB - These studies were designed to investigate the cause of growth retardation during glucocorticoid treatment in rats. In young animals, body weights and amounts of food consumed were measured at two-day intervals, beginning at 29 days of age. Average food intake and food efficiency were calculated. Animals were treated with cortisone (CORT, 5 mg/rat/day, s.c.) or saline (SAL) for eight days between 37 and 44 days. Growth hormone (GH) release by dispersed pituitary cells in response to nine concentrations of GH-releasing hormone (GHRH) were tested by in vitro perifusion at 45 and 73 days. As previously shown, CORT caused a cessation of growth during the treatment period, and body weight failed to catch up. Food efficiency was decreased during CORT treatment. All parameters of in vitro GH release including basal GH secretory rate, overall GH response to GHRH, and the GHRH concentration-response curves were significantly increased by CORT in the 45 day-old animals. An age-related increase in GH release was also observed between the 45 and 73 day saline-treated animals. These results support the hypothesis that glucocorticoids inhibit growth by induction of changes in food metabolism and GH secretion. The effect on the pituitary gland itself paradoxically involves an increase in GH secretory capacity in response to GHRH. PMID- 1895669 TI - Effect of puromycin on metanephric differentiation: morphological, autoradiographic and biochemical studies. AB - Effect of aminonucleoside of puromycin (PAN) on metanephric development and proteoglycans (PGs) was investigated. Murine metanephric tissues, obtained on the thirteenth day of gestation, were exposed to PAN in a culture medium for one to seven days and processed for morphological, histochemical and immunofluorescent studies. For tissue autoradiographic and biochemical studies, kidneys were labelled with a precursor product of PGs, that is, [35S]-sulfate. A generalized decrease in the glomerular population along with swelling and deformation in the ureteric bud branches was observed. These changes were accompanied with a diminution in the total incorporated radioactivity and a reduction in the autoradiographic grains, especially over the tips of ureteric bud branches. Sepharose CL-4B chromatography revealed a major high molecular weight PG (Mr greater than 2.5 x 10(6], and a relative increase in the chondroitinase-ABC sensitive PGs. The media PGs were of relatively smaller size. Immunoprecipitation experiments with [35S]-methionine-labeled tissues and immunofluorescent studies revealed a significant decrease of PGs in metanephric tissues, while type IV collagen and laminin were relatively unaffected. Significant glomerular changes included failure in differentiation of the visceral epithelial foot processes, formation of villi and in maturation of glomerular basement membrane. The latter was seen as fragments of extracellular matrices interspersed among undifferentiated podocytes and had reduced staining with ruthenium red--a dye marker for the PGs. This deficiency of PGs was confirmed by electron microscopic autoradiography, where a reduction in the number of silver grains was observed. The fact that the PAN-induced cellular and extracellular alterations were associated with perturbances in biosynthesis of PGs, suggests that the morphogenetic regulators, that is, PGs play a vital role in various differentiation processes involved during metanephric development. PMID- 1895670 TI - Distribution of pyruvate carboxylase along the rat nephron: an immunological and enzymatic study. AB - Antibodies against purified rat-kidney-cortex pyruvate carboxylase were raised in rabbits. These polyspecific antibodies recognize pyruvate carboxylase enzymes alone without cross reactivity with other carboxylases as detected by immunoblotting. The abundance of pyruvate carboxylase in the various renal fractions was measured by ELISA and its activity by the fixation of [14C]CO3H-. The results were corroborated by a combination of immunocytochemistry and transmission electron microscopy. A good correlation was found between the enzymatic activity and the quantity of enzyme contained in each fraction. The kidney-cortex pyruvate carboxylase was primarily located in proximal tubules, in accord with its important role in gluconeogenesis. PMID- 1895671 TI - Disassociation between glomerular hyperfiltration and extracellular volume in diabetic rats. AB - The relationship of the development of glomerular hyperfiltration in diabetes to changes in extracellular fluid volume has not been previously examined. To accomplish this task, male Wistar rats were chronically cannulated in the bladder, femoral artery and vein. Control measurements of glomerular filtration rate (GFR), renal plasma flow (RPF), extracellular fluid volume (ECF), and urinary sodium excretion were performed on two separate days prior to infusion of streptozotocin (65 mg/kg body wt i.v.). After infusion of streptozotocin, the IDDM rats were separated into two groups: untreated IDDM group of rats and IDDM rats treated with insulin at doses sufficient to normalize blood glucose (Ultralente, 2 to 8 IU/day). A third group of normal non-diabetic rats served as time controls. Measurements of renal function occurred at 1, 4, 7, 11, and 15 days after infusion of streptozotocin. Blood glucose in the non-diabetic measurement period averaged 137 +/- 30 mg/dl and increased from 412 +/- 55 after 24 hours in the untreated diabetic rats to 533 +/- 33 mg/dl after 15 days of IDDM. The time controls and the insulin-treated diabetic rats did not differ in blood glucose values at the time measurements were performed. Glomerular filtration rate increased from 1.0 +/- 0.1 to 1.7 +/- 0.1 ml/min/100 g body wt by day 15 in the untreated diabetic rats with significant increases in GFR within 24 hours. GFR of both time controls and the insulin-treated IDDM rats did not significantly vary during the time of the study. The increase in GFR in the untreated IDDM group was associated with a concomitant increase in RPF.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1895672 TI - Blood pressure and tubuloglomerular feedback mechanism in chronically salt-loaded spontaneously hypertensive rats. AB - Experiments were performed to qualitatively characterize the effects of tubuloglomerular feedback (TGF) inhibition by chronic salt loading on salt sensitivity of blood pressure in spontaneously hypertensive rats (SHR). After two weeks of salt loading, systolic blood pressure (SBP) was significantly exacerbated and plasma volume (PV) was expanded in salt-loaded SHR compared with those in control SHR (SBP: 182 +/- 1 vs. 159 +/- 2 mm Hg; PV: 4.38 +/- 0.06 vs. 4.04 +/- 0.03 ml/100 g body wt, respectively). Plasma volume of WKY was also but only transiently expanded by salt loading, whereas plasma volume expansion in SHR had persisted over the entire dietary treatment period. TGF activity was assessed as the maximal reduction of single nephron GFR (SNGFR) on increasing loop of Henle perfusion rate from 0 to 40 nl/min using previously collected tubular fluid from salt-loaded rats (TFs) or control rats (TFc). Maximal TGF response in salt loaded SHR with TFs was 14.9 +/- 2.9% and 57.8 +/- 2.6% with TFc. In control SHR the responses were 16.9 +/- 2.5% with TFs and 52.7 +/- 2.9% with TFc. In salt loaded WKY the response with TFs were 3.1 +/- 1.6% and 37.4 +/- 2.8% with TFc. And in control WKY, the response with TFs were 8.2 +/- 1.9% and 40.8 +/- 2.8% with TFc, respectively. These results indicate the TGF resetting in chronically salt-loaded SHR and WKY is caused by the activation of humoral TGF inhibitory factor. The suppression of TGF in SHR was, however, far more variable and, on average, less than in WKY.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1895673 TI - Diet, vitamin D and vertebral mineral density in hypercalciuric calcium stone formers. AB - To elucidate the pathophysiology of dietary calcium independent hypercalciuria, 42 calcium stone formers (Ca SF) were selected because they had on free diet a calciuria greater than 0.1 mmol/kg/day. For four days they were put on a diet restricted in calcium (Ca RD) by exclusion of the dairy products. They collected 24 hour urines on free diet and on day 4 of Ca RD as well as the two-hour fasting urines on the morning of the day 5 and the four-hour urines passed after an oral calcium load of 1 g, for measurement of creatinine, Ca, PO4, urea and total hydroxyprolinuria (THP). On day 5 fasting plasma concentrations of Ca, PO4, intact PTH, Gla protein, calcidiol and calcitriol were measured. The patients were firstly classified into dietary hypercalciuria (DH, 18 patients) and dietary calcium-independent hypercalciuria (IH, 24 patients) on the basis of the disappearance or not of hypercalciuria on Ca RD. Then the patients with IH were subclassified into absorptive hypercalciuria (AH) because of normal fasting calciuria (8 patients) and into fasting hypercalciuria (16 patients). Fasting hypercalciuric patients were subsequently divided according to the PTH levels into renal hypercalciuria (RH, 1 patient) with elevated fasting PTH becoming normal after the Ca load and undetermined hypercalciuria (UH, 15 patients) with normal PTH levels. Furthermore, their vertebral mineral density (VMD) was measured by quantitative computerized tomography which was normal in DH (91 +/- 6% of the normal mean for age and sex) but was decreased in IH to 69 +/- 4%. No difference in VMD was observed between AH and UH. Urinary excretions of urea, phosphate and THP was higher in IH than in DH and comparable in AH and UH. Sodium excretion Ca RD was the same in all groups and subgroups as well as the plasma parameters. Plasma calcitriol was increased in IH and DH comparatively to normal in spite of normal plasma calcidiol. Calciuria increase after oral calcium load, an index of Ca absorption, was higher in IH than in controls and comparable in IH and DH as well as in the three subgroups of IH. From these data and correlation studies in IH it is concluded: (1.) VMD is decreased in Ca stone formers with IH but not in those with DH, making the distinction of these two groups of hypercalciuria patients clinically relevant.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1895675 TI - Role of duplex scanning for the detection of atherosclerotic renal artery disease. AB - To assess the accuracy of renal artery duplex scanning for the purpose of diagnosing atherosclerotic renal artery stenosis, we compared the findings of renal arteriograms to the results of duplex scanning in 41 patients. Using an increase of renal artery peak systolic flow velocity of greater than 180 cm/sec, duplex scanning was able to discriminate normal from diseased renal arteries with a sensitivity of 95% and a specificity of 90%. Using the principle that blood flow velocity across a stenosis is roughly proportional to the degree of stenosis, it appeared that a ratio of the peak velocity in the renal artery to the aorta (RAR) of greater 3.5 predicted a greater than 60% diameter reduction of that renal artery, which is felt to be a significant stenosis. Forty-eight vessels were classified as having a greater than 60% diameter reduction by arteriography. Using the RAR of greater than 3.5, duplex scanning agreed in 44 renal arteries (sensitivity 92%). In the 26 renal arteries where arteriography showed a less than 60% diameter reduction, duplex scanning agreed in 16 vessels and correctly detected a focal narrowing in nine of the remaining ten vessels. Ten of 11 occluded renal arteries were correctly identified by duplex scanning. Duplex scanning determined the location of the renal artery lesion with an accuracy of 95% (kappa 0.74). Since duplex scanning can accurately demonstrate and locate focal renal artery stenosis, we believe it may become an accurate screening test for renovascular hypertension.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1895674 TI - Modulation of the secretion of potassium by accompanying anions in humans. AB - In animals, secretion of potassium (K) in the cortical collecting duct (CCD) is modulated by the properties of the accompanying anion. In humans, results are inconclusive as previous studies have not differentiated between a kaliuresis due to a rise in the concentration of K from one due to an increase in the volume of urine. Our purpose was to study the effects of chloride (Cl) and bicarbonate on the secretion of K in the CCD in humans using the transtubular K concentration gradient (TTKG), a semi-quantitative index of secretion of K in the terminal CCD. After control blood and urine samples were obtained, all subjects ingested 0.2 mg fludrocortisone to ensure that mineralocorticoids were not limiting the secretion of K. The anionic composition of the urine was varied using three protocols: Normal subjects (N = 11) ingested cystine and methionine to induce sulfaturia; nine subjects with a contracted ECF volume (to lower the concentration of Cl in the urine) were also studied during sulfaturia following the ingestion of cystine and methionine; 13 normovolemic subjects were studied during bicarbonaturia following the ingestion of acetazolamide. When the concentration of Cl in the urine was greater than 15 mmol/liter, sulfate had no effect on the TTKG. With lower concentrations of Cl in the urine, the TTKG rose 1.5-fold. The TTKG rose 1.8-fold in the presence of bicarbonaturia despite concentrations of Cl in the urine that were greater than 15 mmol/liter, suggesting that bicarbonate has additional effects on this K secretory process. At comparable concentrations of sulfate and bicarbonate in the urine, the TTKG was increased only with bicarbonaturia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1895676 TI - Cytokine- and LPS-induced synthesis of interleukin-8 from human mesangial cells. AB - The cytokine neutrophil-activating peptide-1/interleukin-8 (NAP/IL-8) activates neutrophils (PMN) and elicits selective diapedesis of PMN into the extracellular space. The glomerular mesangial cell (MC) is a specialized pericyte that controls glomerular filtration and synthesizes and responds to a variety of cytokines. Because of its location within the glomerulus, the MC is in a pivotal position to orchestrate events underlying immune injury. Since immune-injured glomeruli have been shown to produce NAP/IL-8 activity in vitro, we assessed whether lipopolysaccharide (LPS)- or cytokine-activated MC might be a source of this activity. Pure human MC, devoid of monocyte/macrophage and fibroblast contamination, were grown by explant from collagenase-treated glomeruli. Human recombinant interleukin-1 alpha (IL-1 alpha, 20 ng/ml), IL-1 beta (50 ng/ml), tumor necrosis factor alpha (TNF, 100 ng/ml) and lipopolysaccharide (LPS, 10 micrograms/ml) stimulated release of a neutrophil chemotactic factor from cultured MC. Both concentrated (fivefold) and unconcentrated MC supernatants stimulated directed neutrophil migration under agarose at a level similar to that of the bacterial chemotactic factor, FMLP. In contrast, unstimulated MC conditioned media and IL-1 alpha, IL-1 beta. TNF and LPS in medium alone did not directly induce PMN migration. Molecular sizing studies using sequential membrane ultrafiltration identified significant TNF-stimulated, MC-derived chemotactic activity in the 3000 to 10000 kD fraction. An anti-NAP/IL-8 monoclonal antibody, 46E5, significantly inhibited PMN chemotaxis stimulated by TNF-stimulated, MC conditioned media in a dose-dependent manner.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1895677 TI - Pathogenesis of nephrolithiasis post-partial ileal bypass surgery: case-control study. The POSCH Group. AB - Between 1975 and 1983, 838 patients were randomized into the Program on the Surgical Control of Hyperlipidemias (POSCH) trial: 417 to standard medical care and 421 to partial ileal bypass (PIB) surgery. During the course of the trial, an increased incidence of kidney stone formation was found in the surgery group (4%/year) as compared to the control group (0.4%/year). A matched triplet case control study was conducted to assess the possible causes for the increased incidence of kidney stones. Three groups were studied: PIB stone-formers (S); PIB non-stone formers (N); and non-PIB, non-stone formers in the control group (C). Initially, 162 patients (54 triplets) were selected. Ten percent of the patients declined to participate which resulted in a sample size of 146 patients. The PIB patients had statistically significant (P less than 0.05) lower levels of serum vitamin D metabolites; lower urine volume, pH, citrate, magnesium, carbon dioxide, and sulfate, and higher urinary oxalate, ammonia and relative supersaturation for calcium oxalate and uric acid than the control patients. Although S and N had similar results, those S with no prior history of stones had a higher calcium oxalate supersaturation than similar N with a negative prior history of stones (P less than 0.025). Based on these results, all PIB patients appear to be at risk for kidney stone formation. The combination of reduced urinary volume and calcium oxalate precipitation inhibitor substance with increased calcium oxalate relative supersaturation produced an increase in nephrolithiasis risk in the PIB groups. PMID- 1895678 TI - Additive and synergistic effects of cyclosporine metabolites on glomerular mesangial cells. AB - Out of the 29 cyclosporin (Cs) metabolites defined so far, 10 representative ones were isolated from bile of liver grafted patients, purified by HPLC, and their structure specified by FAB-MS and 1H NMR. These were used to determine the growth inhibitory effects on Sprague Dawley rat glomerular mesangial cells (MC). Metabolite dilutions were added to cultured MC for 72 hours and [3H]-thymidine incorporation was measured. A 50% growth inhibition by single metabolites (M) on MC was achieved at the following concentrations (mg/liter): Cs: 1.25; M21: 6.0; M18: 9.0; M26: 10.5; M1: 10.8; M8: 10.8; M17: 12.5; M13: greater than 20.0; M25: greater than 25.0; M203-218: greater than 50.0; H355: greater than 50.0. The activity was correlated to the degree of metabolization as the group of six "active" compounds included four primary metabolites (hydroxylated or demethylated derivatives of Cs: M21, M18, M1, M17), whereas the four "inactive" compounds exclusively were secondary metabolites (demethylated, hydroxylated and/or oxidized primary metabolites: M13, M25, M203-218, H355). Combinations of active metabolites with or without Cs resulted in an additive antiproliferative effect. Although single metabolite activities are not relevant in vivo, already combinations of three (M1 + M17 + M18) or four metabolites (M17 + M18 + M21 + H355) resulted in a significant growth inhibition at concentrations of the participating metabolites measured in urine of liver transplanted patients. Moreover, significant synergistic activities were determined with combinations including secondary metabolites. A final set of experiments discharged unspecific cytotoxic effects. The inhibition of MC [3H]-thymidine incorporation was completely reversible and moreover, direct mesangiolysis was excluded for both single and combined metabolite actions. Thus, considering rat MC proliferation as an initial kidney cell model system for subsequent, more detailed studies measuring functional parameters, we have demonstrated that activities of single metabolites are related to their chemical structure. More importantly, mimicking to some extent the patients' situation, combinations of metabolites at concentrations occurring in vivo reduced MC proliferation in culture in an at least an additive fashion, suggesting that side effects of Cs treatment might be attributed to combined Cs metabolite actions. PMID- 1895679 TI - Neurological and neuropathological sequelae of correction of chronic hyponatremia. AB - The effect of correction of chronic hyponatremia at different rates was studied in 91 rats maintained at a plasma [Na+] of 112 +/- 1 mmol/liter for 19 +/- 1 days. Hyponatremia was corrected into normal ranges (140 to 145 mmol/liter) using three different methods. Rats corrected by water restriction achieved normal plasma [Na+] by 2.1 +/- 0.2 day and had a maximal (4 hr) correction rate of 1.0 +/- 0.1 mmol/liter.hr; rats corrected by water diuresis achieved normal plasma [Na+] by 1.6 +/- 0.1 day and had a maximal correction rate of 2.8 +/- 0.2 mmol/liter.hr; rats corrected by hypertonic saline infusion achieved normal plasma [Na+] by 5.4 +/- 0.3 hr and had a maximal correction rate of 5.7 +/- 0.4 mmol/liter.hr. A fourth control group was not corrected. No demyelinative lesions were found in the brains from the uncorrected rats, whereas the occurrence of such lesions in the brains of the corrected rats was highly correlated with the maximal rate of increase in plasma [Na+] (r = 0.68, P less than 0.001), and to a lesser degree with the magnitude of the increase in plasma [Na+] over the first 24 hours of correction (r = 0.41, P less than 0.001). Brain myelinolysis was first observed in animals whose maximal (4 hr) rate of correction exceeded 1.75 mmol/liter.hr, and the incidence of demyelination increased progressively in rats with more rapid rates of correction. Similarly, myelinolysis was first observed in rats whose magnitude of correction at 24 hours exceeded 16 mmol/liter and also increased in rats with larger 24 hour magnitudes of correction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1895680 TI - Calcium oxalate nephrolithiasis: defective oxalate transport. PMID- 1895682 TI - [Endoscopic papillosphincterotomy in the treatment of stenosing papillitis and choledocholithiasis]. PMID- 1895681 TI - [The diagnostic and surgical problems in chronic pancreatitis due to biliary calculosis]. AB - Proceeding from personal clinical experience gained during many years of studies, the authors discuss the diagnostic and surgical problems of biliopancreatitis. In recent years biliary calculosis has been basic etiologic factor in 70 per cent of the cases; 76.8 per cent of the patients had complaints of long standing, while in the rest the history was shorter. The duration did not correspond to the morphologic findings. Only 43 per cent of the patients had clinical symptoms suggestive of accompanying pancreatitis, and echographic examination helped to establish the diagnosis in only 21 per cent of the cases. Two thirds (64 per cent) were patients in advanced and senile age, 5.8 per cent had severe preoperative complications and 52 per cent had systemic diseases affecting organs other than the liver and pancreas. The operations were primary in 169 patients (82 per cent) and repeat in 38 (18 per cent). The remote results were very good in 82 per cent, good in 9 per cent and satisfactory in 9 per cent. It is considered that treatment of chronic biliopancreatitis keeps on being surgical; endoscopic manipulations rather seldom produce ultimate therapeutic effect. PMID- 1895683 TI - [Cholelithiasis, cholecystectomy and colorectal cancer--a retrospective analysis]. AB - The authors analyzed a series of 421 patients with colorectal cancer after preliminary review of the current literature and the modern theories of the origin of the disease. The patients have been treated at the Department of Propedeutics of Surgical Diseases, Research Institute of Surgery, for the period 1984-1990, and special accent was placed on the study of the relation of colorectal cancer to cholelithiasis and cholecystectomy. It was shown that 1.19 per cent of all patients had been cholecystectomized at mean 10.6 years back and 6.65 per cent had pre-existing or accompanying biliary calculosis with mean duration of symptoms 16.4 years. A major relationship was found between morbidity from colorectal cancer, on the one hand, and patient sex and biliary calculosis, on the other. Eighty nine per cent of the patients with colorectal cancer and with biliary calculosis treated by cholecystectomy were women and 20.3 per cent of the women with colorectal cancer had biliary calculosis and had been cholecystectomized. Attention is focused on the current practical requirements of the prophylaxis of colorectal cancer--adequate attitude to biliary calculosis, feeding habits, specifying cases at risk and their observation. PMID- 1895684 TI - [The type, volume and interval between operations in deep burns of the lower extremities]. AB - The most appropriate type and extent of the operations and the intervals between them in deep burns of the lower extremities are specified on the basis of experience with 600 operations performed on 416 patients. The most common operation was free skin autotransplantation, performed in 636 cases (96.36 per cent). The most appropriate extent of the operations is considered a 660 sq cm surface area of the autografts. This was used in 213 operations (57.26 per cent). The number of operations depended on the surface area of the deep burn. In burned area of up to 10 per cent the operations were two, up to 20 per cent--three and more than 20 per cent--more than four. In patients with burned surface up to 20 per cent the interval between the second and the third operation was within the range from 18 to 50 days and in burns involving more than 20 per cent surface- between 13 and 16 days; the last operations were performed 26 to 30 days later after the state of well-being of the patients had been stabilized. PMID- 1895685 TI - [Villous adenomas of the major duodenal papilla: apropos a case]. AB - Proceeding from a review of the literature and the personal observation of a case of tubulovillous adenoma of the large duodenal papilla, which had undergone malignant degeneration, the authors outline the diagnostic problems in this pathology. Since its clinical manifestations are not specific enough, it comes into consideration only after the possible more common diseases in the region of the right subcostal space have been ruled out. Preoperative diagnosis can be established mainly with fiber duodenoscopy. The demand from the pathologist is not only to give a histologic diagnosis, but to define the biologic nature of the tumor formation, since this predetermines the operative approach. It is sometimes difficult to give answer to the latter requirement even through and intraoperative express biopsy specimen examination. PMID- 1895686 TI - [The effect of electroacupuncture analgesia on the plasma levels of cortisol and aldosterone in orthopedic operations]. AB - The effects of electroacupuncture on plasma cortisol and aldosterone levels in patients undergoing orthopedic operations were studied. Plasma cortisol and aldosterone levels were measured at three stages. Moderate activation of the hypothalamo-pituitary-adrenal system is considered an adjustment response of the organism to the operative trauma, with stable hemodynamic parameters. The total amount of analgetic drugs which the patients received during the postoperative period was three times lower than that in the control group given neuroleptanalgesia; during electroacupuncture analgesia (EAPA) opioids were not applied. It is considered that the use of EAPA lowers the degree of the stress reaction in surgical trauma, providing adequate analgesia and neurovegetative protection of patients during orthopedic operations and in the early postoperative period. PMID- 1895687 TI - [Free dermatoplasty in traumatic amputations of the fingers]. AB - Twenty-two patients with 27 traumatic amputations of the fingers comprise the study group. The fingers of the right hand were affected in 19 cases and of the left hand in 8. The traumatic injuries of the right hand affected mostly the II. and the III. finger, whereas the left hand injuries affected almost with equal frequency the II. to the V. finger. Primary free skin plasty was performed after sparing surgical processing without shortening of the bone. In 3 cases this was done late after the inflammatory changes in the conquassated tissues had disappeared. Primary cure after postoperative hospital stay from 7 to 15 days was observed. Early rehabilitation was attempted. The results, both cosmetic and functional were satisfactory. Fine sensitivity was impaired during the early period after the operation, but was improved after the sixth month. Of the 11 tested patients who reported for control 6 months to 5 years after the operation, 10 were able to distinguish two points of pressure at 6 mm distance from one another and could fulfil their professional work without difficulties. Taking into account that of all cases of traumatic injuries to the hand only 4 per cent report to specialized hospital departments, the author considers free skin plasty a method of choice for the general surgical units over all other plastic methods of non-free skin plasty which are also presented and illustrated in the paper. PMID- 1895689 TI - [Experience with hernioplasty by N. I. Kukudzhanov's method]. PMID- 1895690 TI - [A comparative study of the level of plasma prolactin in women and men undergoing operations under halothane and neuroleptanesthesia]. AB - Twenty women and 20 men subjected to urologic operations comprise the study group. Ten women and 10 men were operated under halothane anesthesia and 10 women and 10 men--under neuroleptanesthesia. Plasma prolactin levels were determined before induction in anesthesia, and 30 and 60 minutes after the onset of the operation. The mean plasma prolactin level in women exceeded the upper normal limit at the first determination before induction in anesthesia. During the operation, both in women and in men, with either type of anesthesia there occurred statistically significant rise in the mean plasma prolactin, more pronounced in women than in men. In women, the rise in plasma prolactin was greater during operations performed under halothane anesthesia and in men--under neuroleptanesthesia. PMID- 1895688 TI - [Changes in the osmotic resistance of the erythrocytes in thermal trauma and the role of free-radical oxidation]. AB - Reduced erythrocyte osmotic resistance against the background of elevated blood level of TBA-reactive products was recorded in experimental thermic injury (of IIIa-IIIb degree, involving 15-20 per cent of the body surface). Under the influence of alpha-tocopherol, parallel with the restriction of free-radical oxidation (FRO) activity, there was a rise in erythrocyte membrane osmotic resistance. FRO participation in the mechanisms of reduced erythrocyte osmotic resistance in thermic injury is discussed. PMID- 1895691 TI - [Malignant non-Hodgkin's lymphomas in abdominal surgery: apropos 3 cases of Burkitt's lymphoma]. AB - On the occasion of three observations of the extremely rare and malignant Burkitt's lymphoma, the authors record their 7-year experience in the operative treatment of 22 patients with non-Hodgkin's malignant lymphomas. Proceeding also from data available in the current literature, the most frequently encountered syndrome-complex is presented, the knowledge of which is of major importance for the early diagnosis, resp. for the results of combined treatment. The possibilities of the operative treatment are evaluated. In the authors' series it was radical in 31.8 per cent of the cases with 13.6 per cent early postoperative lethal outcome and 5.2 months average postoperative survival rate. Proceeding for the rarity of the disease in everyday surgical practice and that it is poorly known, but has become a nosologic entity of increasing interest, the authors have devoted the first part of their article to a discussion on the basic characteristics of non-Hodgkin's malignant lymphomas and the modern achievements of their treatment. PMID- 1895692 TI - [A case of bilateral kidney tumor combined with staghorn calculi and skin cancer]. AB - A rare case of bilateral renal tumor with benign clinical evolution, associated with staghorn calculosis and skin cancer, is reported. Delayed operative treatment was due to difficulties in establishing the diagnosis, controversial results of the sonographic and X-ray examination and lack of cooperation by the patients. The right kidney and regional lymph nodes were removed; metastases were verified on histologic examination of the lymph nodes. After the operation the patient received complex radio-, chemo- and hormonal therapy. Basocellular skin cancer which later developed was cured by contact radiotherapy. PMID- 1895693 TI - [Chronic pancreatitis--the current aspects of its surgical treatment]. PMID- 1895694 TI - [A case of adenocarcinoma of the ileum complicated by ileus]. PMID- 1895695 TI - [A case of biliary peritonitis following the withdrawal of a Kehr drain from the d. choledochus]. PMID- 1895696 TI - [A rare combination of acute pancreatitis and dissecting aortic aneurysm]. PMID- 1895697 TI - [The exteriorization of the basilic vein as a vascular approach in patients on periodic hemodialysis]. PMID- 1895698 TI - [The technical equipment for transcholedochal-transduodenal operations on the terminal choledochus]. PMID- 1895699 TI - [A minor program for statistical analysis]. PMID- 1895700 TI - [The correlation between the activity of free-radical peroxidation and erythrocyte hemolysis in experimental thermal trauma]. AB - Increased concentration of the products of red-cell free-radical oxidation (FRO), i.e. of malondialdehyde (MDA) and of Schiff bases in red cells and of their hemolysis was recorded in the acute period of experimental thermic injury. Alpha tocopherol applied after thermic injury suppressed FRO and restricted red cell hemolysis. A strong positive correlation was recorded between hemolysis and MDA (r = 0.97) and between hemolysis and Schiff bases (r = 0.88). This high-grade positive correlation between hemolysis and content of secondary and end products of FRO, as well as their decrease after alpha-tocopherol treatment give grounds to admit that activated peroxidation processes in red cells play a definite role for destabilization of their membranes. The role of hemolysis for secondary FRO activation and for implication of the whole organism in the overall pathologic process, the burn disease, is discussed. PMID- 1895701 TI - [Surgical laser papillosphincterotomy]. AB - The still rather limited application of laser in biliary surgery is pointed out, to experience gained so far, including personal one, laser is being used in extirpation of the gall bladder, for treatment of the bladder bed, for choledochotomy and for papillosphincterotomy. Laser papillosphincterotomy was performed in a 65-year-old female patient--the first case in this country. This method has some advantages--adequate hemostasis, absence of reactive edema, early re-establishment of bile flow, adhesion of the incision edges. PMID- 1895702 TI - [Retroperitoneal sarcomas]. AB - Sixteen years experience (1974-1989) is recorded with the treatment of 18 patients with retroperitoneal sarcoma. The tumor was palpable in all. Four syndromes could be differentiated in these patients: gastrointestinal, renal, vascular and neurologic. All modern methods of diagnosis were applied: ultrasonography in 12 patients, computer tomography--13, angiography--3, X-ray examination of the gastrointestinal tract--7, gamma-renography--5, urography--2. Radical operative intervention is considered treatment of choice, followed by radio- or hemotherapy. Radical extirpation of the tumor was performed in 10 patients (55.5 per cent). Extended operative interventions with resection of adjacent organs were performed in 4 patients (22.2 per cent). After histologic verification 10 patients (55.5 per cent) were subjected to chemotherapy and 7 to radiotherapy. Postoperative case fatality rate was 17 per cent (3 patients died). Four patients 22.2 per cent) had relapse of the tumor between the first and the third year. PMID- 1895703 TI - [3 cases of acute postoperative pancreatitis]. AB - After a brief review of the literature the authors present three cases of acute postoperative pancreatitis in patient operated for different reasons with lethal outcome. In one patient the complication developed after duodeno hemipancreatectomy and is the only patient with such complication (2 per cent) of 50 patients in whom radical operation was performed for cancer of the pancreas over the period Jan. 1983-May 1990. The current aspects of the etiology, treatment and above all of the prophylaxis of acute postoperative pancreatitis, which is a very serious postoperative complication with very high case fatality rate (up to 77 per cent, according to data in the literature) are discussed. PMID- 1895704 TI - [The place of interventional ultrasound in urology]. AB - The search for new methods of diagnosis, treatment and prognosis and their introduction in practice is a stable process in world urologic practice. It was not until after the first echographic apparatuses were produced in the fifties that the introduction of interventional ultrasound in urology became feasible. The authors set themselves the task to study and summarize the possibilities of this method for treatment of diseases of the kidneys, upper urinary tract, bladder and prostate. Renal cysts were diagnosed by ultrasound in 312 patients; in 229 of them percutaneous puncture was performed under ultrasound control. To reduce relapses, different sclerosing substances were applied, peak success being obtained with tetraolean. For establishing the exact cause of obstruction of the upper urinary tract the authors used antegrade pyelography under ultrasound control in 92 patients. Percutaneous nephrostomy for drainage of the upper urinary tract, a new endourologic operation was performed in 67 patients. To raise the radical approach to transurethral resection of the prostate and of bladder tumors, intraoperative transurethral ultrasound control was adopted for all patients operated by this technique. PMID- 1895705 TI - [Burns during pregnancy]. AB - The course and treatment of burns during pregnancy in 12 women were studied. The patients were in 15 to 35 gestation week and burns affected 14 to 90.5 per cent of the body surface. Inverse relation was found between severity of burns and fetal survival. After treatment 6 women survived. All who died had more than 50 per cent of the body surface burned. Ten children were born alive, 4 of them prematurely. Four children died (2 of them were still-born and 2 prematurely born). Treatment of these patients (especially drug and operative) should conform to the pregnancy and should be conducted in close collaboration with obstetrician. PMID- 1895706 TI - [The modern diagnosis and treatment of chronic nonspecific prostatitis]. PMID- 1895707 TI - [Granulomatous orchitis]. AB - Granulomatous orchitis is a rare inflammatory disease of poorly understood etiology. Its differentiation from testicular tumor is difficult and is resistant to antibiotic therapy. Five cases of this disease are reported. In 3 of them orchiectomy was performed and in 2 the testis was preserved after biopsy specimen examination. Relapses or injury to the contralateral testis were not recorded during the follow-up period. A review of the literature is made and the etiopathogenesis, clinical and therapeutic aspects of this disease are discussed. PMID- 1895708 TI - [The treatment of gastroduodenal ulcers with the IaV'-1 apparatus]. PMID- 1895709 TI - [Hemorrhoidal disease and the concomitant changes in the rectosigmoid]. AB - Hemorrhoids is the most common disease in coloproctology, and rectoromanoscopy is a valuable tool of diagnosis. Of a total of 1614 patients examined at the proctologic consulting room of the Department of Gastroenterology at the Medical Academy in Sofia, hemorrhoids had 609 (37.8 per cent). External were 2 per cent of the hemorrhoids, internal 81.1 per cent and external + internal 15.9 per cent. Characteristic finding in internal hemorrhoids were the swelling in the anal canal, localized along 3, 7 and 11 hours of the clock dial in knee-elbow position of the patient. Endoscopic symptoms of hemorrhoid malignization were ulceration, thickening and infiltration of the mucosa at the bottom of the erosion. Hemorrhoids were frequently associated with accompanying diseases (52.6 per cent) which aggravated the patients complaints. They may occasionally be the cause of symptomatic hemorrhoids. PMID- 1895710 TI - [The treatment of calculi in the iliac segment of the ureter by extracorporeal high-energy shockwave lithotripsy]. AB - Experience is recorded with the treatment of calculi in the iliac segment of the ureter by extracorporal lithotripsy with high-energy stroke waves with lithotriptor of the firm "Dornier", model HM-3. For a period of 2 1/2 years 18 patients at mean age 38 years have been treated. Retrograde catheterization was always performed before lithotripsy. Successful reposition was achieved in 6 patients. In all others lithotripsy was performed in prone position. Special supporting cushions were manufactured and used; they helped for a more stable position of the patient on the stand, facilitate calculus positioning, the load to the knee joints is reduced, the fluoroscopic time is shortened, thus reducing the radiation load to patient and attending personnel. All patients received antibacterial and spasmolytic therapy. The mean length of stay in the clinic was 3.2 days. The results were good in 94.1 per cent of the cases. No early or late complications of urologic or other nature were observed. PMID- 1895711 TI - [Autotransplantation with mesh grafts in extensive burns]. AB - Proceeding from experience with 667 operations during the past 9 years in patients with burns affecting more than 20 percent of the body surface, the author analyses the importance and frequency with which reticulate autografts are used. The advantages of manual and mechanically perforated grafts are compared. The decisive importance of this type of grafts in the operative treatment of large-scale burns is emphasized. PMID- 1895712 TI - [The treatment of burn wounds with silver sulfadiazine]. AB - Results of clinical and bacteriologic studies of the preparation dermazin, produce of LEC, Ljubljana, Yugoslavia are reported. Dermazin is a 1 percent silver sulphadiazin creme. It has very good antiseptic qualities which allow to maintain for a long time a low count of bacterial colonization in a burn wound. This furnishes opportunity for performing necrectomies. A disadvantage of the cream is its moistening effect on necroses, which renders difficult their removal by chemical necrolytic agents. In comparison with the 0.5 percent silver nitrate solution used so far, dermazin has the following advantages penetrates better in the wound; more convenient form for local application; better tolerated by patients; does not stain skin and bedspread; causes no electrolyte disturbances; has strong bactericidal effect against most common gram-positive and gram negative bacteria. PMID- 1895713 TI - [The treatment of severe forms of diffuse suppurative peritonitis]. PMID- 1895714 TI - [The content of corticosterone, adrenaline and noradrenaline in the organs of rats in endotoxic shock and being treated with vitamin E]. PMID- 1895715 TI - [A case of postoperative peritonitis treated by laparostomy]. PMID- 1895716 TI - [Nephrectomy for kidney tumor following an operation for calculi]. PMID- 1895717 TI - [An instrument for transcystic papillary calibration and papillary dilatation]. PMID- 1895718 TI - [Our experience with the surgical treatment of acute gynecological diseases]. AB - Experience is recorded in the treatment of acute gynecological diseases based on a series of 61 patients operated in the Clinic of Propedeutics of Surgical Diseases at the Research Institute of Surgery in Sofia for the period Jan. 1983 April 1990. They comprise 6.08 per cent of all emergency cases. The most common gynecological pathology was, as follows: 59 per cent ovarian cysts, 11.5 per cent adnexitis, 26.2 per cent adnexitis + pelvioperitonitis, 6.6 per cent extrauterine pregnancy, etc. The early postoperative results were very good--zero case fatality rate, absence of serious complications, 6.6 per cet suppurations. Taking into account also the very good remote results, the authors point to the trivial appraisal of the surgical activity and the need of thorough evaluation of the patient's fertility, all the more that 78.7 per cent of the women were younger than 39. In the light of the current trends in gynecological practice, the authors specify the indications and contraindications for surgical interventions in these diseases. PMID- 1895719 TI - [Development of impaired vision in mentally handicapped children]. AB - The aim of the following study was 1) to show the incidence of ophthalmic disorders in severely visually and mentally handicapped children retrospectively 2) to follow up the change in visual acuity over at least 2 years prospectively 3) to look at the effect of therapeutic concepts. 270 children of the "Blindeninstituts-stiftung Wurzburg" were followed up between 1960 and 1987. ad 1) Optic atrophy was the leading cause of visual impairment (24%) followed by cataract and retinopathy of prematurity (both found in 17%), malformations of the anterior segment (12%), cortical amblyopia (8%) and refractive error (6%). Strabismus was an additional finding in 38% of the children often associated with nystagmus. Convergent and divergent strabismus had the same incidence. ad 2) Visual acuity improved in 30% of cases of cortical amblyopia, in 40% of refractive errors and in 30% of optic atrophy. In cases of cataract there was a slight improvement in 20%. In 24% of aphakia a secondary glaucoma was observed. In cases of malformations of the anterior segment and ROP the visual acuity remained stable on a low level. The cases of ROP were advanced and had not received any surgical treatment. A deterioration in vision as often seen after surgical intervention was observed in 20% of ROP. In respect of the high incidence of refractive errors and orthoptic problems in multiple handicapped children they should be seen as early as possible by an ophthalmologist. Detection of a congenital cataract soon after birth as well as complications of other disorders should help to prevent blindness. The remaining visual perception is especially important for the handicapped child to communicate and move about. PMID- 1895720 TI - [Lens changes following pneumatic retinopexy: preliminary results of linear densitometry image analysis of Scheimpflug photographs two months after operation]. AB - The small degree of morbidity and a better postoperative visual acuity are the advantages of pneumatic retinopexy in comparison to encircling procedures in the treatment of retinal detachment. The injection of air or gas into the vitreous cavity can theoretically induce a cataract postoperatively. Two months after pneumatic retinopexy (SF6-gas) Scheimpflug photography and microdensitometric evaluation of the negative were performed on 22 pairs of phacic eyes showing changes in the transparency of the lens. The deterioration of transparency in the operated eye was small but higher than that of the non-operated eye. Due to the short follow up period no prognosis is possible as to the future lens transparency changes. PMID- 1895721 TI - [Results of pseudophakic retinal detachment surgery]. AB - Between 8/81 and 9/89 2658 patients underwent retinal detachment surgery at the university eye hospital Erlangen/Nurnberg. From this number there were 30 (= 1.1%) pseudophakic retinal detachments consisting of 14 males and 16 females. Minimal age was 48, maximal 89 years, average age was 70.9 years. There were 4479 extracapsular cataract extractions with implantation of a posterior chamber lens performed in the same interval at our eye hospital. Out of this 4479 extracapsular cataract extractions we found 9 patients (= 0.2%) with pseudophakic retinal detachment. In our investigated group we found preoperative risk factors resulting in a pseudophakic retinal detachment consisting out of myopia, latticelike degeneration of the retina and contusion bulbi. Intraoperative risk factors are the rupture of the posterior capsule and vitreous prolapse. A postoperative risk factor is YAG-laser-capsulotomy. We observed a pseudophakic retinal detachment with patients undergoing YAG-laser-capsulotomy after minimal 30, maximal 880 and 372 days in average. Out of 30 patients 17 (= 66.6%) were treated successfully with the first operation. The success rate summed up to 83.2% after one re-operation. With 17 out of 30 patients we had to apply extensive endoophthalmic vitreous and retinal surgical techniques (cerclage, pars plana-vitrectomy, silicone oil instillation). PMID- 1895722 TI - [Volumetric analysis of the optic papilla using laser scanning tomography. Parameter definition and comparison of glaucoma and control papilla]. AB - We performed a three-dimensional structure analysis of the optic disc in 65 eyes of 65 patients (38 glaucoma patients, 27 control-group patients) using laser scanning tomography. Patients classified as glaucoma showed at least 3 points with a relative scotoma of -10 db loss or greater compared to age matched controls on static 30 degrees computerized perimetry. Control-group patients showed no relative scotoma outside the blind spot area compared to age matched controls. One way analysis of variance revealed statistically significant differences between the glaucoma (G) and the control-group (C) for excavation volume (+0.57 +/- 0.37 mm3 G/0.31 +/- 0.27 mm3 C, p less than 0.01), for the 3rd moment of the frequency distribution of excavation depths readings (-0.01 +/- 0.12 G/-0.13 +/- -0.09 C, p less than 0.001), area ratio (0.75 +/- 0.15 G/0.57 +/ 0.16 C, p less than 0.001), depth area ratio (0.35 +/- 0.24 G/0.18 +/- 0.12 C, p less than 0.001). A stepwise discriminant analysis classified 32 of 38 (84.2%) glaucoma discs and 21 of 27 (77.8%) control-group discs by a linear combination of 5 out of 15 topographic parameters. The results suggest that a combination of topographic parameters may provide an objective optic disc classification. PMID- 1895724 TI - [Real time eye tracking--principles and quantification]. AB - Tracking and quantification of eye movements in real time is a prerequisite for future computer assisted laser positioning for diagnostic or therapeutic purposes. Principles of TV-image processing are described: tracking of contrasts and pattern recognition tracking by object correlation; their relevance for tracking retinal targets is illustrated using authentic video material. For practical use, the pattern recognition technique qualifies better. The influence of the systems variable parameters on retinal target pursuence is described. Automatic target pursuence of authentic eye movements reached tracking success rates well above 90% thus outperforming manual tracking by one order of magnitude. PMID- 1895723 TI - [Octopus perimetry in neuro-ophthalmologic diseases. A contribution to the problem of optimal program choice based on 427 cases]. AB - From the patient population of the University Eye Clinic Basel 427 cases, who had been tested with the Octopus perimeter 201 because of neuro-ophthalmologic problems, were retrospectively examined. Above all it was interesting to find out, which program to use in order to get a maximum degree of information with a minimum of examinations. The quantitative programs 31 to 34 gave most often the clinically relevant information concerning the opticus- and chiasma affections. The only exception was the anterior ischemic opticoneuropathy where the semiquantitative program 07 delivered the better information. With supragenicular affections program 07 delivered by far, and most often, the clinically relevant information. Because of our results we can make the following recommendations: if a pregenicular lesion is suspected, it is sensible to use quantitative programs with a homogenous test point distribution within 30 degrees testing area. If a supragenicular lesion is suspected, the registration of the total extension of the defect is of greater practical value than a quantitative threshold determination. In this case, the survey program 07 is suitable. If visual disturbance is present, without a hint of its location, it is recommended to start with the survey program 07 and thereafter, according to test results, specifically continue with a quantitative program. PMID- 1895725 TI - [Diagnosis of glaucoma using fundus spectrometry in areas outside the papilla]. AB - As a result of the statistical evaluation of spectra on the basis of discriminant analysis, it can be stated that spectrometric measurements on fundus areas are suited for glaucoma diagnosis also outside the papilla. For early recognition of glaucoma, measurements of the papillomacular bundle are more sensitive than measurements in the parapapillary region. Late stages of glaucoma and normal findings are most reliably separated by measurements in the parapapillary region. With increasing severity of the glaucoma, the spectrum of the macular pigment can be demonstrated in the papillomacular bundle. A spectrometrically recognizable lack of erythrocytes documents an impaired retinal microcirculation. PMID- 1895726 TI - [Recurrent and persistent nummuli after epidemic keratoconjunctivitis]. AB - Three observations of typical patients with persistent and recurrent nummuli after epidemic keratoconjunctivitis serve--pars pro toto--to demonstrate that longterm therapy with high-dosed topical steroid offers no therapeutic solution. This experience and other disadvantages of steroids in KCE (dry eyes) lead us to recommend not to apply topical steroids in KCE unless an adenovirus specific antiviral agent has become available for basic antiviral therapy. PMID- 1895727 TI - [Keratoconus in Alagille syndrome]. AB - We report on a 20 year old white male with growth retardation, secondary hypothyroidism, typical facies, skin lichenification and brachydactylia due to arteriohepatic dysplasia. We found a bilateral keratoconus with corneal scaring but none of the other known ophthalmological findings. A keratoplasty was performed in the right eye. The pathogenesis of the keratoconus is unknown. PMID- 1895728 TI - [Unusual course of hypernephroma metastasis]. AB - 11 years after removal of a kidney because of hypernephroma a choroidal metastasis of this tumor grew. Clinically an inflammatory process had been suspected, thus leading to late correct diagnosis. The clinical and histological findings are presented. In the overall statistic of ocular metastasis seen in the university-eye-hospital in Hamburg, hypernephromas hold the 3rd place in the rank list of the most common primary tumors. Thus, in case of a suspected ocular metastasis, in differential diagnosis a hypernephroma should be excluded. PMID- 1895729 TI - [Donor tissue for keratoplasty. Report of experiences by the Hamburg cornea bank]. AB - We report on or experience with the evaluation, preservation and clinical grafting of corneal donor tissue. From a total of 2274 documented donor corneae about 1535 specimens were subjected to a corneal preservation procedure. Refrigerated storage of donor tissue has been completely replaced by corneal tissue culture. On the basis of the tissue culture techniques of Sperling, improved methods to culture and evaluate donor tissue were developed. Using organ culture as a preservation system, post mortem intervals for donor tissue could be extended to 50 hours. Organ culture in this respect serves as a viability test, as the donor endothelium is examined before culture and again before grafting. Thus, primary graft failures caused by degenerative endothelial cell changes could be avoided. Using phase microscopy, we developed criteria for the prognostic evaluation of corneal endothelium without vital staining. From a total number of about 1101 clinical grafts, 712 were taken from corneal preservation and 389 from refrigerated globes. Since 1985 exclusively tissue-cultured donor corneae are used for transplantation. A clinical follow-up of 327 patients showed cultured tissue to be at least equal to "fresh" corneal grafts. PMID- 1895730 TI - [Exudative reaction after implantation of an artificial lens]. AB - Results of clinical observation over post-operative period and degree of exsudative reaction in 240 patients (262 eyes) with implantation of intraocular lenses are analysed. Three types of postoperative course are distinguished: a reactive, postoperative with early exsudative reaction and postoperative with late exsudative reaction. Immunologic investigations (determination of percentage and absolute amount of T-lymphocytes in peripheral blood, reaction of blast transformation of lymphocytes on phytohemagglutinin and on antigens of the lens, the choroid and the retina) performed in 184 patients with artiphakia allowed to make a conclusion that postoperative course with late exsudative reaction is dependent on preliminary sensibilization of the body to proteins of eye tissues and has immune nature. The treatment with indometacin proved to be effective and prevented development of late exsudative reaction in 40 patients with implantation of intraocular lenses. PMID- 1895731 TI - [A normal stereo-test for assessing work capacity]. AB - A new natural stereotest was designed for measuring stereoacuity gradually. Borderline values were established. It is possible to separate persons without normal stereoscopic vision from persons with satisfactory, good or excellent stereoacuity in a very short time. This new stereo-normtest can be used for fitness examinations. PMID- 1895732 TI - [Pathology of the corneal endothelium in bullous keratopathy following iris clip lens implants]. AB - 12 patients developed pseudophakic bullous keratopathy 2 to 7 years following i.c. cataract-extraction with implantation of 4-loop iris clip lenses necessitating perforating keratoplasty. To study the pathogenesis of pseudophakic bullous keratopathy the corneal endothelium of the excised button was investigated light-microscopically after vital staining of the endothelium. Additionally the surface of the explanted intraocular lenses were examined by the method of Wolter. The result is a central cell density of the excised corneal buttons between 179 and 867 cells/mm2. Large cell-free areas were always found indicating that a disturbance of the endothelial barrier function is the major reason for corneal decompensation. A relation between inflammatory cell deposits on the IOL-surfaces and the endothelial decompensation was not apparent. As the main reason for endothelial decompensation a chronical mechanically induced endothelial cell loss is supposed leading to disturbances of the endothelial barrier function. To prevent a repeated corneal decompensation it is recommended to remove iris-clip-lenses during the procedure of perforating keratoplasty. PMID- 1895733 TI - [Cold dosage in retinal cryotherapy using echography]. AB - In cases of obscured view of the fundus a precise timing of cryotherapy of the retina is not possible. In order to avoid complications from overtreatment we use the real time ultrasonography for monitoring the spreading ice in relation to the retina. PMID- 1895734 TI - [Clinical aspects, differential diagnosis and histopathology of spontaneous subretinal mass hemorrhage]. AB - This report describes the clinico-histopathologic correlation of three eyes (of three patients aged 80, 82 and 86 years) with massive subretinal hemorrhage. Two blind eyes were enucleated because of a painful therapy-resistant angle-closure glaucoma, one eye was suspected to have a melanoma of the choroid. Bleeding was predisposed by anticoagulant therapy for systemic problems in one patient and by thrombocytopenia in another patient. Histopathologically a disciform macular degeneration was found in all three eyes as the suspected source of bleeding. The differentiation of subretinal bleeding is from malignant melanoma of the choroid which is made possible by ultrasonic examination of the eye. PMID- 1895735 TI - [Validity and reproducibility of confocal corneal measurements]. AB - In order to verify reproducibility and validity of confocal measurements of the cornea we examined a well known biological model: Increasing corneal thickness under hypoxic conditions during contact lens wear. The method verified increasing thickness with high significance. In addition, reproducibility was determined within a range of 5 mu. As a result, confocal measurements proof to be a powerful tool for topographical reconstruction of corneal shape. PMID- 1895736 TI - [Improved reproducibility of computer-assisted structural analysis of the optic papilla]. AB - Longitudinal monitoring of the optic disc structure by means of automated nervehead analysis (Optic Nerve Head Analyzer, ONHA) can facilitate the diagnosis of ongoing glaucoma. Until recently, however, longitudinal disc monitoring was complicated by considerable fluctuations of the results measured with the Optic Nerve Head Analyzer. Since March/1990 there is a new software version of the equipment (ONHA-plus). The determination of disc parameters using ONHA-plus proved to be significantly more reliable than the determination using the former ONHA: the mean fluctuation of the neuroretinal rim area measured on 18 normal eyes was 0.07 mm2 (ONHA-plus) compared to 0.094 mm2 (ONHA); the variation coefficient dropped from 7.9% (ONHA) to 4.6% (ONHA-plus). A further improvement of the reproducibility can be obtained by double examinations, because the mean examination time using ONHA-plus is about half as long as the examination time using ONHA. Moreover, ONHA-plus enables the recognition and elimination of unreliable results caused by poor image quality. Due to this increased reliability the ONHA-plus system is a considerably improved equipment for the clinical monitoring of glaucoma patients. PMID- 1895737 TI - [Effect of pressure-induced ischemia on oxygen supply in the retinal capillary area. Results of a mathematical model]. AB - This paper attempts to obtain a better understanding of the oxygen supply to tissue cells of the optic nerve head by describing all phases of the release, diffusion and consumption process by means of a mathematical model. As a result the oxygen partial pressure reduction induced by intraocular pressure elevation- as it occurs in glaucoma--seems to be mainly influenced by a pressure-induced lowering of the average blood velocity in the retinal capillaries. A reduction of this velocity to a fourth of its normal value even makes the oxygen partial pressure at the venous capillary wall drop below the critical level necessary for maintaining cell activity. Furthermore our calculations allow us to conclude that an involvement of the retinal capillary network supplied by the central retinal artery should not be neglected in glaucoma. PMID- 1895738 TI - [Ocular manifestations in a patient with Cockayne syndrome and simultaneous reduced DNA repair]. AB - A 14 year old white boy presented with the typical clinical findings of Cockayne syndrome. Photodermatosis was known since the third week of life. He had disproportionate short stature with a short trunk, long limbs and flexion contractures of the large joints. He also was cachectic and prematurely aged. He had a typical facies. The hearing was slightly impaired. The prominent ocular findings were corneal opacifications, salt and pepper like retinal pigment epithelial changes and optic atrophy. On fibroblast culture the DNA repair activity is usually normal in patients with Cockayne syndrome. The DNA repair activity in our patient however was markedly reduced to 25% of normal. On lymphocyte culture a significantly increased 4-nitroquinoline-1-oxide sensitivity (cytotoxicity and increased break-rate) was found. These findings indicate that the boy has a specific variant of Cockayne syndrome with simultaneously reduced DNA-repair activity. PMID- 1895739 TI - [Secondary angle-block glaucoma in posterior scleritis]. AB - Posterior scleritis is an often misdiagnosed disease of the eye. Mainly it appears in elderly women and tends to be recurrent. Symptoms leading to diagnosis are swelling of the eye lids, a red eye, disturbances of the motility and protrusio bulbi. In rare cases you find exudative choroidal or retinal detachment, edema of the macula, or the optic nerve head, and secondary angle closure glaucoma. Often posterior scleritis is associated with general illness as herpes zoster, mixed connective tissue diseases, or Boeck's disease. Differential diagnosis are choroidal tumors as for example, melanoma, hemangioma, and metastases. The typical uveal effusion can also be caused by an arterio-venous fistula, panretinal photocoagulation, buckling procedure for retinal detachment, and by intraocular surgery in general. Especially cyclitis anularis pseudotumorosa has to be considered and shut out. Most important diagnostical means are ultrasound, and CT-scan. The underlying case describes an 81 years old woman that presented with acute angle closure glaucoma, and exudative choroidal detachment of the right eye. The ultrasound and CT-scan investigations confirmed the diagnosis of scleritis posterior. The acute angle closure glaucoma, and the choroidal detachment regressed immediately under the treatment with steroids given locally and systemically. There was no impact of miotics and peripheral iridectomy which both could not avoid recurrence of angle closure glaucoma. PMID- 1895740 TI - [Group G streptococci as pathogens of postoperative endophthalmitis]. AB - We report an exceptional case of fulminant endophthalmitis after uncomplicated extracapsular cataract extraction with posterior chamber lens implantation. The first unusual finding was the causative organisms, group G streptococci. These organisms are commonly found as normal flora of the skin, pharynx and gastrointestinal tract. They are also well known as pathogens of neonatal sepsis, otitis media and pneumonia, but there are only three case reports describing a streptococcus G endophthalmitis. The second unusual finding was the delayed onset of the fulminant endophthalmitis, occurring later than 9 days after surgery. A retrospective analysis of 17 additional cases showed that endophthalmitis occurred either during the first 5 days after surgery or later than 35 days after surgery. If endophthalmitis developed shortly after surgery it progressed rapidly and with intense inflammation. The other cases showed more chronic inflammatory reaction. From the latter finding we conclude that long postoperative monitoring remains necessary even if at first no signs of intraocular inflammation are detectable. PMID- 1895741 TI - [A new instrument for measuring eyelid strength]. AB - Former investigations concerning muscular eyelid strength with dynamic registration revealed great inter- and intraindividual variations. We tried to minimize these influences by using an electronic power register with isometric registration. This is important because lid closing is a complex mechanism of horizontal and vertical movements with continuously changing power vectors. Our new apparatus reduces false results. A normal collective of 114 persons was examined. The results show no statistically significant age- or sex-related differences in lid strength. PMID- 1895742 TI - [Johann Gottfried Zinn--a Franconian anatomist and botanist]. AB - Johann Gottfried Zinn (1727-1759), a franconian anatomist and botanist made important contribution to the anatomy of the eye during his short life span. In his main book "Descriptio anatomica oculi humani" he gave the first detailed and comprehensive description of the anatomy of the human eye. During his professorship at the university of Gottingen the emphasis of his scientific work was in the field of botany. His memory will be kept by the anatomical terms "zonula ciliaris Zinnii" and the circulus arteriosus sclerae = Zinn-Haller's arterial circle. As a botanist Zinn was honoured by the fact that a flower (Zinnie) was named after him. PMID- 1895743 TI - [Possible damage to the eye caused by light from ophthalmologic equipment]. AB - Motivated by numerous findings of the damaging effect of intense light levels on the fundus we measured the spectral radiation of several ophthalmic illuminations and used it to calculate from it the spectral retinal irradiance. To evaluate the thermal hazard, we calculated the resulting temperature rise at the fundus. A measure for biological damage is the percentage of denaturated molecules, which is related to the temperature rise and its duration (essentially identical to the duration of illumination) by the so-called Arrhenius-integral. We used this measure to compare any illumination with experimentally evaluated threshold values for thermal damage. To evaluate the photochemical hazard we compared the spectral retinal irradiance with threshold values for photochemical induced lesions. Furthermore the illuminations were correlated with safety-guidelines likewise distinguishing between thermal and photochemical hazard. Under adverse conditions operation microscopes can present a thermal hazard to the patient's eye. Other ophthalmic illuminations are of less concern in this respect. A similar estimation applies to hazard from photochemical effects. The photochemical hazard can be diminished essentially by reducing the short wavelength bluelight. Qualitatively, maximal permissible exposures according to safety guidelines are consistent with our thermal calculations as well as with photochemical hazard evaluation by comparing spectral retinal light levels with threshold irradiance for photochemical induced lesions. However, since quantitatively safety guidelines estimate the thermal hazard very conservatively, many common ophthalmic illuminations exceed the exposure limits, in some cases even drastically. PMID- 1895744 TI - [Eliminating reflection of intraocular lenses]. AB - Reflections on the refractive surfaces of intraocular lenses can be a nuisance when performing retinoscopy or refractometry. Some patients with IOLs also see reflections which disturb their vision. This article examines the conditions for coating IOLs. It also explains why conventional coating methods cannot be used for IOLs. PMID- 1895745 TI - [Medical technology congress concludes]. PMID- 1895746 TI - [Lens changes following intraocular tamponade in vitrectomy. Linear densitometric image analysis of Scheimpflug photographs 6 months after operation]. AB - A complication arising from vitrectomy is the formation of cataract. As a result of an intra- and postoperative tamponade chosen (BSS, air, SF6-gas, silicon oil) the size and frequency of the cataract varies accordingly. 6 months after vitrectomy Scheimpflug photography and microdensitometric evaluation of the negatives were performed on 30 pairs of phacic eyes showing changes in the transparency of the lens. Following silicon oil tamponade a significant deterioration of transparency (t-test) was observed in the lens nucleus of the operated eye; in the area of the lens in front of the nucleus a marked but not significant deterioration of transparency was discovered following both silicon oil and SF6-gas tamponade. In the case of the area in front of the nucleus following SF6-gas tamponade as well as the whole of the lens following BSS or air tamponade a small but not at all significant difference in lens transparency was apparent after comparison of the operated to the non-operated eyes. PMID- 1895747 TI - Treatment of acute promyelocytic leukemia with all-trans retinoic acid. PMID- 1895748 TI - Leukocytosis in mice following long-term reconstitution with genetically-modified bone marrow cells constitutively expressing interleukin 1 alpha or interleukin 6. AB - Leukemic cells of patients with acute myeloid leukemia have recently been shown to spontaneously produce autostimulatory IL-1 and IL-6. In order to investigate the effects of systemic production of these cytokines on normal hematopoietic cells, mice were engrafted with bone marrow cells infected with high-titer retroviral vectors carrying the murine IL-1 alpha or IL-6 genes and the neomycin phosphotransferase gene. Sustained expression of the introduced IL-1 alpha and IL 6 genes was documented by Northern-blot analysis of RNA from G418-resistant mast cells and T cells, derived from bone marrow and spleen, respectively, of successfully reconstituted mice 6-10 months after transplantation. A single mouse engrafted with IL-1 alpha-infected cells which presented with a dramatic neutrophilic granulocytosis (54-fold elevation in circulating neutrophils) was sacrificed for health concerns 2 months post-transplant. Modest changes in peripheral leukocyte counts (at most a 2-fold rise) were observed in all of the other mice, and they remained healthy throughout the observation period. The majority displayed increased hematopoietic activity in bone marrow and spleen, predominantly granulopoiesis, with moderate lymphoid hyperplasia seen in the spleens of mice constitutively expressing IL-1 alpha. These mouse models provide the opportunity to evaluate the potential of persistent IL-1 alpha and IL-6 expression to contribute to leukemogenic transformation. PMID- 1895749 TI - Decreased DNA polymerase sensitivity to 1-beta-D-arabinofuranosylcytosine 5' triphosphate in P388 murine leukemic cells resistant to vincristine. AB - P388 murine leukemic cells 28.6-fold resistant to vincristine were cross resistant to doxorubicin and etoposide. Although the intracellular ara-CTP in P388 murine leukemic cells resistant to vincristine (P388/VCR) was significantly higher than that in the parent cells, the cytotoxic effect of ara-C was not significantly different between the parent and resistant cells. Therefore, we investigated the DNA synthesis in P388/VCR and its parent cell line using the permeable cell system. The DNA synthesis in P388/VCR cells was less sensitive to ara-CTP and dTTP than that in P388 parent cells. These results suggested that the characteristics of DNA polymerase in P388/VCR cells might change when the cells developed multiple drug resistance. PMID- 1895750 TI - Monoclonal antibodies in myeloid diseases: prognostic use in acute myeloid leukaemia. AB - Bone marrow cells from 109 patients (median age 60) with newly diagnosed acute myeloid leukaemia (AML) were prospectively immunophenotyped (IP) and the prognostic value of monoclonal antibody (MAB) reactivities was analysed to detect differences in complete remission rates and survival, not only between groups of MAB + and - bone marrow cells, but also in cases with or without prominent MAB reactivity as compared to normal BM reactivity of the respective MABs. This approach was based on the assumption that the qualitative expression of antigens is not an all or none phenomenon, but that different degrees of expression of antigens exist. Patients with significantly elevated CD13 (MY7+) cells in bone marrows (CD13 greater than reference value + one standard deviation) (S.D.) showed decreased probability of entering CR (p less than 0.05) and a significantly shorter survival (p less than 0.05). Superior CR rates (p less than 0.05) without difference in long-term survival were seen in patients with low CD33 (MY9) or low HLA-DR expression, while high CD14 (MY4) expression showed a trend towards an adverse factor (p = 0.12). No other antibody reactivities showed differences in CR rates (CD3, CD20, CDw65 (VIM-2) and NAT-9). The more prominent bone marrow expression of CD33 antigen than CD13 (CD33/CD13 greater than 1) correlated to a better chance of entering CR (p = 0.01) and to improved survival (p = 0.002), while the expression of high numbers of VIM-2+ cells was a favourable prognostic factor regarding length of survival (p = 0.002). The importance of a high CD33/CD13 ratio as a positive prognostic factor was evaluated using stratified analysis according to age or leucocyte counts at presentation. In both cases, CD33/CD13 was associated with longer survival (age: p = 0.05, leucocyte counts: p = 0.03). A Cox multiparameter analysis revealed that the CD33/CD13 ratio was a favourable prognostic factor (p = 0.03) together with age (p = 0.001) and leucocyte counts in peripheral blood (p less than 0.01). We conclude that establishing the immunologic phenotype can be of prognostic value in cases of AML, especially with regard to the relationship between the CD33 and CD13 antigens. PMID- 1895751 TI - Effects of inhibitors of protein tyrosine kinase activity and/or phosphatidylinositol turnover on differentiation of some human myelomonocytic leukemia cells. AB - The activities of protein tyrosine kinase and phosphatidylinositol turnover have been found to be associated with cell growth and differentiation. We examined the effects of some inhibitors for these biochemical activities in human myelogenous leukemia cells. Genistein, which is known to inhibit the activities of protein tyrosine kinase, phosphatidylinositol turnover and topoisomerase II, induced nitroblue tetrazolium (NBT) reduction and lysozyme activity in ML-1, HL-60 and U937 cells. Morphological studies showed that genistein-induced differentiation of myeloblastic ML-1 cells into promyelocytes and of promyelocytic HL-60 cells into mature granulocytes. The differentiation-inducing effect of genistein was augmented by addition of 1 alpha,25-dihydroxyvitamin D3 (VD3) or retinoic acid, VD3 being more effective than retinoic acid. Methyl 2,5-dihydroxycinamate, a protein tyrosine kinase inhibitor, had only a weak effect in inducing differentiation of ML-1 cells. On the other hand, psi-tectorigenin was more effective than genistein in inducing the differentiations of ML-1 and HL-60 cells. Psi-tectorigenin is reported to inhibit phosphatidylinositol turnover without inhibiting protein tyrosine kinase. Thus modulation of phosphatidylinositol turnover might be more important than that of protein tyrosine kinase activity for differentiation of some myelogenous leukemia cells. PMID- 1895753 TI - The effects of lithium on the growth and phorbol ester (TPA) induced differentiation of two HL-60 sublines. AB - Two sublines of a human promyelocytic cell line, HL-60, were used to study the effect of lithium on TPA (12-o-tetradecanoylphorbol-13-acetate) induced macrophage-like differentiation. Although these sublines, HL-60 M and HL-60 JE, had different growth rates, both showed enhanced proliferation when treated with 5 mM lithium (128 +/- 2 and 141 +/- 1% in comparison to controls after 5 days of incubation, respectively). Treatment of the sublines with TPA for 72 h resulted in macrophage-like differentiation (assessed by cell adhesion) of about 90% at 10 nM TPA in HL-60 JE, whereas a maximum of 50% at 100 nM TPA was obtained in HL-60 M. Differentiation was also confirmed by non-specific esterase activity. However, incubation of both sublines with TPA and 5 mM lithium revealed that lithium has little or no effect on the macrophage-like differentiation of the HL-60 cell line. PMID- 1895752 TI - Inhibition by vitamin D3 of erythroid differentiation of human leukemia line cells induced by transforming growth factor beta or erythroid differentiation factor (activin A). AB - Erythroid differentiation of human leukemic cell lines (HEL, KU812F and K562) was induced by their treatment with transforming growth factor beta (TGF-beta) or erythroid differentiation factor (EDF/Activin A). Their erythroid differentiation was markedly inhibited by vitamin D3, dexamethasone or 12-O-tetradecanoyl-phorbol 13-acetate, which are known to induce monocytic differentiation of leukemic cells. These results suggest that inducers of monocytic differentiation may switch off cellular regulatory mechanisms for induction by TGF-beta and EDF of erythroid differentiation of leukemia cells. PMID- 1895754 TI - Characterization of a new cell line (ESKOL) resembling hairy-cell leukemia: a model for oncogene regulation and late B-cell differentiation. AB - A B-lymphoblastoid cell line ESKOL, composed of differentiated cells resembling hairy-cell leukemia (HCL) has been established from the peripheral blood (PB) of a HCL patient. Morphologically, ESKOL cells share several features with HCL B cells. Flow cytometric analysis revealed that ESKOL cells express HC2, CD21, PCA 1, CD24, FMC7, and CD25. Analysis by Northern-blot hybridization indicated that cultured cells expressed the oncogenes c-myc, H-ras and c-fos. RNA from 3T3 cells transfected with ESKOL DNA hybridized with H-ras and c-fos DNA probes. The ESKOL cells cultured in the presence of increasing concentrations, of alpha interferon demonstrated a decrease in the rate of cellular growth and an increase in the expression of CD21, CD25, FMC7 and PCA-1. Scanning electron microscopy revealed that cells incubated in the presence of alpha interferon underwent membranous changes with a loss of villosity. These observations suggest that IFN tends to drive HC out of their developmental arrest towards maturation. PMID- 1895755 TI - Cellular kinetics of transforming growth factor-beta induced hemoglobin accumulation in the HEL erythroleukemia cell line. AB - Transforming growth factor-beta 1 (TGF beta 1) can induce hemoglobin accumulation in a clone of the human HEL erythroleukemia cell line. This clone has previously been designated as HEL-T. The effect of TGF beta 1 was reversible and it had to be continuously present for the maximal number of cells to become positive for hemoglobin. The TGF beta 1 effect was blocked by phorbol ester and partially blocked by the calmodulin antagonist W-7, but not by dexamethasone. Simultaneous exposure to gamma-interferon, IL-1, IL-6, IL-3 and GM-CSF had no significant effect on TGF beta induced hemoglobin accumulation. However, when TGF beta was combined with TNF alpha, it was observed that there was approximately a 10-15% reduction in benzidine-positive cells. Cell-cycle analysis revealed no significant long-term alterations in any of the compartments. Analysis of the TGF beta 1 effect on 10 different HEL-T-derived clones revealed that the number of benzidine-positive cells ranged from 12 to 70% after 5 days of continuous exposure. Cell proliferation was similarly differentially affected. Another HEL cell line, designated as W-HEL, did not accumulate hemoglobin in the presence of TGF beta 1, but did have an increase in alpha-globin RNA expression. PMID- 1895756 TI - The synergistic effect of hemin and transforming growth factor-beta on hemoglobin accumulation in HEL erythroleukemia cells. AB - Transforming growth factor-beta (TGF beta) and hemin can both independently induce hemoglobin accumulation in the human HEL erythroleukemia cell line. The combination of these two agents resulted in a synergistic effect in the production of hemoglobin. On day 1, following exposure to both hemin and TGF beta, approximately 35% of the cells had accumulated hemoglobin, as evidenced, by benzidine staining. Whereas, when treated alone with either agent, the percentage of benzidine-positive cells was less than 10%. By day 5, approximately 70-80% on the cells treated with the combination were benzidine-positive. Cell surface analysis showed that the combination of TGF beta and hemin increased the expression of CD34, CD64, glycophorin A, and GPIIb-IIIa(CDW41). Cell proliferation was decreased by the combination. PMID- 1895757 TI - Response to trans-retinoic acid in an AMLM3 patient resistant to cis-retinoic acid. PMID- 1895758 TI - Factor V in cerebrospinal fluid of leukemic patients on intrathecal chemotherapy. PMID- 1895759 TI - Why I don't have a living will. PMID- 1895761 TI - Medical staff credentialing: a prescription for reducing antitrust liability. PMID- 1895760 TI - Does legislating hospital ethics committees make a difference? A study of hospital ethics committees in Maryland, the District of Columbia, and Virginia. PMID- 1895762 TI - Medical determination (and preservation) of decision-making capacity. PMID- 1895763 TI - Remarks on the judge's role and moral certainty. PMID- 1895764 TI - Medical decision-making and the "right to die" after Cruzan. PMID- 1895765 TI - Medical decision-making and the right to die after Cruzan. PMID- 1895766 TI - A judge's perspective: the New York rulings. PMID- 1895767 TI - Identifying appropriate decision-makers and standards for decision. PMID- 1895768 TI - The effect of the treatment setting on the decision-making process: acute care hospitals and emergency services. PMID- 1895769 TI - Impact of the Cruzan case on medical practice. PMID- 1895770 TI - Why withdrawal of life-support for PVS patients is not a family decision. PMID- 1895771 TI - The authority of families to make medical decisions for incompetent patients after the Cruzan decision. PMID- 1895772 TI - Between isolation and intrusion: the Patient Self-Determination Act. PMID- 1895773 TI - The role of state legislatures after Cruzan: what can--and should--state legislatures do? PMID- 1895774 TI - Life and death choices after Cruzan. PMID- 1895775 TI - Advance directives under state law and judicial decisions. PMID- 1895777 TI - Comparison of the Maclura pomifera lectin-binding glycoprotein in late fetal and adult rat lung. AB - The lectin, Maclura pomifera agglutinin (MPA), binds to alpha-galactose residues of glycoproteins on the apical surface of type II alveolar cells. It has recently been shown to bind to macrophages. We isolated the cell surface glycoprotein, which binds the MPA lectin, from fetal and adult rat whole lung to determine if changes in this glycoprotein occur during development from fetal to adult life. The glycoprotein was purified from whole lung cell membranes by lectin affinity chromatography that resulted in 10(5)-fold enrichment. The MPA binding glycoproteins from both fetal and adult lung had the same apparent molecular weight of 170 kD as determined by sodium dodecylsulfate-polyacrylamide gel electrophoresis. Amino acid analysis revealed similar composition of the fetal and adult proteins. Two-dimensional peptide maps of the 170 kD proteins isolated from fetal and adult lung were also similar. These data indicate that the glycoprotein that binds MPA to lung cell membranes does not change during this stage of development. Our method for the isolation of this glycoprotein can be used for the generation of antibodies or other molecular probes for further study of this protein. PMID- 1895776 TI - Glutathione and inflammatory disorders of the lung. AB - Glutathione (GSH) is an essential tripeptide present in most eukaryotic cells. Because of its sulfhydryl group, GSH is a versatile molecule capable of protecting cells against oxidants and toxic xenobiotics. However, it also plays key roles in multiple metabolic pathways, such as the synthesis of certain leukotrienes, proteins, and DNA precursors as well as the activation of enzymes, the regulation of immune responses and others. Not only is GSH synthesized by cells for local use but it also participates in an elaborate intercellular exchange process regulated by the gamma-glutamyl cycle. Extracellular GSH in plasma and in alveolar epithelial lining fluid is thus subject to variations according to the degree of expression of gamma-glutamyl cycle enzymes and the rate of consumption of GSH by electrophilic molecules. Bronchoalveolar lavage has allowed us to observe many of these variations of GSH within the extracellular environment of the normal and diseased human lung. Studies of lung GSH have lead to a better understanding of pathogenic processes and have stimulated investigations of novel therapeutic approaches in lung inflammatory disorders. PMID- 1895778 TI - Bronchoconstriction and delayed rapid shallow breathing induced by cigarette smoke inhalation in anesthetized rats. AB - Bronchomotor and ventilatory responses to inhalation of cigarette smoke (50% concentration, 6 ml) were studied in anesthetized and vagotomized Sprague-Dawley rats. Low-nicotine cigarette smoke did not cause any detectable delayed response, whereas high-nicotine cigarette smoke induced rapid, shallow breathing, and a marked increase in airway resistance (RL). The increase in f reached a peak (delta f = 43 +/- 8%) at the 5th breath after the onset of smoke inhalation, preceding both the decrease in VT (delta VT = -27 +/- 4%) and the increase in RL (delta RL = 89 +/- 19%); the latter 2 reached their peaks at approximately the 10th breath, displaying a similar temporal pattern of responses between them. The bronchomotor response to high-nicotine cigarette smoke was slightly attenuated but not prevented by prior administration of isoproterenol (0.2 mg/kg, intravenously [iv]), nor was the smoke-induced rapid, shallow breathing. In contrast, prior administration of mecamylamine (0.9 mg/kg, iv) completely abolished both the bronchomotor and ventilatory responses to smoke inhalation, indicating that nicotine is the primary causative agent responsible for these changes. PMID- 1895780 TI - [Clinical and methodological considerations in the quantification of estrogen and progesterone receptors using monoclonal antibodies in breast cancer]. AB - BACKGROUND: The aim of the present study was to provide information on several clinical and methodological aspects of the measurement of the contents of estrogen (ER) and progesterone (PgR) receptors in breast tumoral tissue using monoclonal antibodies. METHODS: The contents of ER and PgR were measured in 94 tumor specimens of breast carcinoma from pre- and postmenopausal women by the classical method of dextran-charcoal (DC) and an enzyme immunoassay (EIA) with monoclonal antibodies against receptors. RESULTS: The most remarkable results were: a significant difference for ER depending on the menopausal status, an increasing concentration of ER and PgR with age, a greater frequency of the phenotypes ER positive (+)-PgR (+) and ER negative (-) -PgR (-), a lower frequency of positive than negative receptors in the tumors measuring more than 10 cm, a greater presence of tumors with negative than with positive receptors in those located in the lower half of the breast, and the high diagnostic sensitivity of ER and PgR measurement with this method. CONCLUSIONS: There was a remarkable difference in contents of total ER in breast tumors from pre- and post menopausal women. This finding confirms that these tumors may have a different hormone modulation and a different capacity for protein induction depending on the menopausal status. PMID- 1895779 TI - Elastase activity in bronchoalveolar lavage fluid from oxygen-exposed, Pseudomonas-infected baboons. AB - The adult respiratory distress syndrome is a major cause of morbidity and mortality in critical care patients. Lung injury in this syndrome is frequently associated with lung infection. The combined insults result in an influx of neutrophils and damage to the pulmonary epithelium. We investigated whether active neutrophil elastolytic activity was present in the bronchoalveolar fluid in baboons with mild or moderate hyperoxic lung injury and infection. Group A (N = 7) was exposed for 6 days to FIO2 = 0.8 and then inoculated by intratracheal bolus with Pseudomonas aeruginosa strain DGI-R130 (PA); the FIO2 was reduced to 0.5. Group B (N = 6) was exposed to similar concentrations of inspired oxygen but inoculated with buffered saline. Antibiotics included parenteral penicillin and topical gentamicin and polymyxin B. All 3 were given continuously in group B but stopped 24 h prior to PA inoculation in group A. Bronchoalveolar lavage fluid was collected 1 week before oxygen administration, when the FIO2 was reduced (day 6 or 7) and prior to necropsy (day 11). Hemodynamic, pulmonary function, microbiological, and biochemical variables were studied. Injured, infected animals (group A) had significant elevations of mean pulmonary artery pressure and decreases in total lung capacity and PaO2 compared both to baseline and to group B at day 11. At autopsy, group A had significant increases of bronchoalveolar lavage fluid (BALF) neutrophils and bacterial pathogens. Elastase levels in BALF (equal to 0 at baseline) rose to 136 +/- 98 ng/ml in group A vs. 6 +/- 14 ng/ml in group B. The elastase was inhibited by inhibitors of serine proteases including ones specific for neutrophil elastase. On Sephacryl S-300 chromatography the elastase activity eluted near human alpha 2-macroglobulin and separated from other proteolytic activity. These studies demonstrate a significant level of elastase in BALF from injured, infected baboons compared to injured, uninfected animals. PMID- 1895781 TI - [A descriptive epidemiological study of ulcerative colitis in a community hospital (1985-1989)]. AB - BACKGROUND: The incidence of ulcerative colitis (UC) shows a marked geographical variation. It is high in Anglo-Saxon and Scandinavian countries, while in Mediterranean countries the available data on its epidemiological features are few. Spain is not an exception. METHODS: The new cases of UC diagnosed during the period 1985-1989 in the Hospital de Sabadell (a reference center of an area with a markedly industrial population of 343924) were retrospectively evaluated. The definitive diagnosis of UC required a negative fecal microbiological study and findings in colonoscopy and biopsy consistent with UC. RESULTS: During the study period 68 new cases of UC were diagnosed, representing a mean yearly incidence of 3.95/10(5) population, and 5.26/10(5) considering only the adult population (age greater than 14 years). No significant differences were found (p greater than 0.05) in the sex and age distributions, although the male/female ratio was 1.06. In 84% of cases UC was limited to the rectum and/or distal colon, with a low frequency of pancolonic forms (5%). In 70% of patients UC was classified as a low severity disease. CONCLUSIONS: Although the estimation of incidence only from hospital cases underestimates the true incidence, and also considering the limitation of comparing results of studies from several time periods, the incidence of UC in our area is the highest one reported to the present time in Spain and Southern Europe. Nevertheless, it is lower than that in most Northern European countries. PMID- 1895782 TI - [Epidemiology of community-acquired pneumonia in the Health Area I of Navarra]. AB - BACKGROUND: During one year (1988), a protocol study of the community-acquired pneumonias was carried out in patients referred to the Hospital Virgen del Camino in Pamplona (Health Area I or Northern Navarra), so as to have an epidemiological and microbiological knowledge of this disease in this geographic area. METHODS: A clinical protocol, microbiological investigation, 3 blood cultures, Gram stain and sputum culture and serological tests at admission and 20 days later (complement fixing antibodies and indirect immunofluorescence) were carried out. Chest radiographs were carried out on admission, on the third and seventh hospital days and subsequently depending on the evolution. RESULTS: The causative organism was found in 141 of the 225 included patients (62%). Two or more organisms were identified in 19 (8%). In 84 (38%) no microorganism was found. The results for the causative organisms and their frequency were: Pneumococcus 12%, mycoplasma 12%, other bacteria (including Legionella) 11%, Q fever 8%, viruses 7%, and psitaccosis 4%. In 59% of patients there was an underlying disease and 39% developed complications. 4% of patients died. CONCLUSIONS: 22% of the community acquired pneumonias were cared for in the hospital, representing 6% of the admissions to the Internal Medicine Service. The etiologic diagnosis was made in 62% of the community-acquired pneumonias. 23% were of bacterial origin (including Legionella) and 31% were nonbacterial. There was a high incidence of pneumonias caused by Mycoplasma pneumoniae and Coxiella burnetii. PMID- 1895783 TI - [Antibiogram and its results]. PMID- 1895784 TI - [Minimal information that should be found in reports about suspected adverse reactions of drugs]. PMID- 1895786 TI - [Future prospects in the treatment of arterial hypertension on the basis of circadian rhythm]. PMID- 1895787 TI - [Heart disease and diabetes]. PMID- 1895785 TI - [Sclerosing cholangitis, papillary stenosis and B-cell lymphoma in a patient with acquired immunodeficiency syndrome]. AB - The case of a 31 year old man who had been intravenous drug abuser for years is reported. He was studied because of abdominal pain, jaundice, a weight loss of 10 kg, and the presence of a subclavicular mass. Biopsy of the mass demonstrated a high-grade B-cell non-Hodgkin's lymphoma, and the patient was classified in group IV-D of the human immunodeficiency virus infection because he had HIV serum antibodies and a reduced CD4/CD8 lymphocyte ratio. Although lymphoma had a good response to chemotherapy, persistent cholestasis led to liver and biliary evaluation. Sclerosing cholangitis and papillary stenosis were found. He has been followed for two years, without evidence of any secondary infectious disease associated to the acquired immunodeficiency syndrome. PMID- 1895788 TI - [Severe neutropenia caused by ticlopidine]. PMID- 1895789 TI - [The role of primary care in hospitalization units at home]. PMID- 1895790 TI - [Neurological complications in topical administration of mydriatics]. PMID- 1895791 TI - [Dapsone syndrome]. PMID- 1895792 TI - [Estimation of the probability of digitalis toxicity using a combination of clinical criteria and blood digoxin levels]. PMID- 1895793 TI - [Simultaneous infection by Coxiella burnetii and Chlamydia psittaci in 2 patients: the problem of psittacosis of non-avian origin]. PMID- 1895794 TI - [Clinical protocols]. PMID- 1895795 TI - [Treatment of recurrent aphthae with thalidomide in patients with acquired immunodeficiency syndrome]. PMID- 1895796 TI - [Abdominal tuberculosis in patients with acquired immunodeficiency syndrome]. AB - BACKGROUND: In individuals with HIV infection, extrapulmonary forms of tuberculosis are considered as opportunistic infections and are included in the diagnosis of AIDS. They often have atypical clinical features. Abdominal participation is uncommon and its diagnosis may be difficult. METHODS: The clinical, radiological and pathological features of patients with a diagnosis of AIDS with abdominal tuberculosis in a series of 254 AIDS cases in a general hospital from 1984 to October 1990 were reviewed. RESULTS: Tuberculosis developed in 104 (41%) of AIDS patients. In 25 (24%) the disease was exclusively pleuropulmonary and in 79 (76%) extrapulmonary tuberculosis was present, either alone or in association. Extrapulmonary tuberculosis was the first opportunistic infection in 66 AIDS cases (26%). The abdominal participation was demonstrated in 19 patients, with the following localizations: lymph nodes (9), liver (8), spleen (5), ileum (1) and peritoneum (1). Four patients with splenic tuberculosis also had multifocal nodular lesions. CONCLUSIONS: Abdominal participation was found in 19 of the 104 AIDS patients with tuberculosis (18%). Lymph node involvement was the most common type. Hepatosplenic tuberculosis had a miliary form or showed multifocal images in echography or computed tomography. PMID- 1895797 TI - [Cerebral hydatidosis. Analysis of a series of 23 cases]. AB - BACKGROUND: The aim of the present study was to contribute to the knowledge of cerebral hydatidosis so as to improve the prognosis of a benign condition with a malignant behavior, as it has a high relapse rate with a high morbidity. METHODS: A retrospective study of cerebral hydatidosis has been carried out in 23 patients, seen at the University Hospital Virgen del Rocio during the last 20 years. The following variables were recorded: 1) Sex and age at presentation; 2) epidemiological data; 3) number, size, localization and rate of growth of cysts; 4) latency period; 5) clinical features; 6) yield of imaging procedures; 7) surgical approaches and medical therapy; and 8) relapses and sequelae. A comparative study was made of patients aged 14 years or less and those above this age. RESULTS: The mean age of the patients was 15.1 +/- 10.3 years (65% were younger than 14 years). 24% were males. 65% came from Extremadura and 74% had a rural background. The latency period was 7.9 +/- 9.2 months (range 15 days-36 months), and it was shorter in children (4.2 +/- 3.8 vs 12.6 +/- 12.7 months) (p less than 0.05). 74% had a single cyst. The cyst size was greater in children (91 +/- 46 vs 67 +/- 35 mm), as it was the rate of growth, particularly in patients younger than 10 years (13.5 +/- 7 vs 9.2 +/- 2 mm/year) (p less than 0.001). 48% had intraparenchymal localization and 70% were in the right hemisphere. In two cases the localization was intraventricular and it was cerebellar in one. Cranial computed tomography was the imaging procedure with the highest yield. The diagnosis was confirmed with pathological examination. In 6 patients (26%) the Dowling and Orlando technique (hydatid delivery) was carried out without subsequent relapses. In 7 cases (30%), and owing to surgical technique difficulties or accidents, puncture and aspiration were carried out, with 4 relapses (57%). In 10 cases cyst rupture occurred, with 6 relapses (60%). The growth rate of the relapses was 9.4 +/- 6.5 mm/month. 87% had severe sequelae, associated with relapses and multiplicity, two patients died (9%). CONCLUSIONS: 1) Cerebral hydatidosis predominates in children and young adult males of a rural background; 2) usually there is a long latency period, which is shorter in children; 3) the size and the growth rate of the cysts is greater in children; 4) computed tomography is the imaging technique with the highest yield; 5) Dowling and Orlando technique is the most effective surgical procedure; 6) the incidence of relapses is high, depending on the type of surgical approach. PMID- 1895798 TI - [Does this patient have systemic lupus erythematosus?]. PMID- 1895799 TI - [The movement of healthy cities]. PMID- 1895800 TI - [Primary ciliary dyskinesia]. PMID- 1895801 TI - [Unilateral exophthalmos and hydronephrosis in a 6l-year-old man]. PMID- 1895802 TI - [Generalized rigidity as a presenting feature of acute primary adrenal insufficiency]. PMID- 1895803 TI - [Importance of age groups as epidemiological parameter of tuberculous disease]. PMID- 1895804 TI - [Usefulness of echocardiography in heart failure]. PMID- 1895805 TI - Esophageal motility disorders and chest pain. AB - Motility abnormalities have long been recognized as a possible esophageal cause of chest pain; however, their exact role and prevalence remain largely unknown. Baseline manometry and the various provocative tests may suggest an esophageal origin, but their yield is low. The recent advent of prolonged ambulatory monitoring of intraesophageal pressure and the assessment of psychological factors are contributing to a clearer understanding of this complex problem. PMID- 1895806 TI - Gastroesophageal reflux disease as a cause of chest pain. AB - Patients with recurrent chest pain free of significant coronary artery disease account for 10% to 30% of patients undergoing coronary angiography. Recent studies suggest that gastroesophageal reflux disease may be very common in these patients. The cause of this chest pain seems to be related primarily to an acid sensitive mucosa regardless of the presence of esophagitis. Unfortunately, a careful history will not distinguish chest pain arising from a cardiac versus an esophageal source. Therefore, all patients must undergo a thorough cardiac evaluation before assuming that acid reflux is the cause of their complaints. Initial gastroenterology evaluation will usually include upper GI endoscopy or barium studies, possibly with acid perfusion (Bernstein) testing, or both. However, the more sensitive and specific test for acid-related disease is prolonged esophageal pH monitoring. This study quantifies the amount of acid reflux but, more importantly, identifies the relationship between chest pain and acid reflux episodes. Patients should be studied in the outpatient setting with emphasis placed on performing activities that replicate their chest pain. Although we presume that acid-induced chest pain responds as well as heartburn to vigorous antireflux regimens, there are few studies to address this issue. Nevertheless, I have had great success in treating these patients with either high-dose H2 blockers or omeprazole therapy. PMID- 1895807 TI - Psychiatric disorders in patients with esophageal disease. AB - Psychiatric disorders have potentially important roles in the manifestations of esophageal disease. A primary causative role for psychiatric factors in the common motility disorders associated with chest pain (esophageal spasm and the nonspecific motor disorders) remains unproven, but psychiatric disorders appear particularly prevalent in this group. In most other esophageal diseases, psychiatric factors interact through recognized psychophysiologic or behavioral mechanisms to affect the clinical presentation. Recognizing the possible levels of interaction has significant therapeutic implications. PMID- 1895808 TI - Microvascular angina. Cardiovascular investigations regarding pathophysiology and management. AB - A significant minority of patients with chest pain who undergo cardiac catheterization are found to have angiographically normal coronary arteries. Over the past 25 years, several studies have shown that a subset have demonstrable abnormalities in coronary flow and cardiac function; however, only a minority of these patients have convincing evidence for myocardial ischemia during stress, and alternative mechanisms have been explored to explain the frequent and debilitating symptoms of pain experienced by the majority of these patients undergoing study. Abnormal visceral nociception appears to be a fundamental abnormality in this population, whether or not demonstrable abnormalities in coronary flow or cardiac function can be demonstrated. PMID- 1895809 TI - Mitral valve prolapse, panic disorder, and chest pain. AB - Mitral valve prolapse is a common cardiac disorder that can readily be diagnosed by characteristic auscultatory and echocardiographic criteria. Although many diseases have been associated with mitral valve prolapse, most affected individuals have the primary form of the disorder. Mitral valve prolapse is an inherited condition commonly associated with myxomatous degeneration of the mitral valve and its support structures. Complications of mitral valve prolapse, including cardiac arrhythmias, sudden death, infective endocarditis, severe mitral regurgitation (with or without chordae tendineae rupture), and cerebral ischemic events, occur infrequently considering the wide prevalence of the disorder. Panic disorder is a specific type of anxiety disorder characterized by at least three panic attacks within a 3-week period or one panic attack followed by fear of subsequent panic attacks for at least 1 month. It too is a common condition with a prevalence and age and gender distribution similar to that of mitral valve prolapse. Panic disorder and mitral valve prolapse share many nonspecific symptoms, including chest pain or discomfort, palpitations, dyspnea, effort intolerance, and pre-syncope. Chest pain is the symptom in both conditions that most commonly brings the patient to medical attention. The clinical description of chest pain in patients with mitral valve prolapse is highly variable, possibly reflecting multiple etiologies. Chest pain in panic disorder is usually characterized as atypical angina pectoris and as such bears resemblance to the chest pain commonly described by patients with mitral valve prolapse. Multiple investigative attempts to elucidate the mechanism of chest pain in both conditions have failed to identify a unifying cause. Review of the literature leaves little doubt that mitral valve prolapse and panic disorder frequently co-occur. Given the similarities in their symptomatology, a high rate of co-occurrence is, in fact, entirely predictable. There is, however, no convincing evidence of a cause-effect relationship between the two disorders, nor has a single pathophysiologic or biochemical mechanism been identified that unites these two common conditions. Until specific biologic markers for these disorders are identified, it may be impossible to do so. The lack of a proven cause-and-effect relationship between mitral valve prolapse and panic disorder and the absence of a unifying mechanism do not diminish the clinical significance of the high rate of co-occurrence between the two conditions. Primary care physicians and cardiologists frequently encounter patients with mitral valve prolapse and nonspecific symptoms with no discernible objective cause who fail to respond to beta-blockade. Panic disorder should be considered as a possible explanation for symptoms in such patients.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1895810 TI - The relationship between esophageal motility disorders and microvascular angina. AB - Patients with unexplained chest pain have caused investigators in cardiology, gastroenterology, and psychiatry to find abnormalities with overlap among the three specialties. This article reviews the data concerning the potential interrelation of chest pain of cardiac or esophageal origin. PMID- 1895811 TI - Validating studies for panic disorder in patients with angiographically normal coronary arteries. AB - This article describes validating studies for diagnosing panic disorder in some patients with angiographically normal coronary arteries (NCA) and chest pain. Psychiatric interviews of 94 such patients showed that 34% met the diagnostic criteria for panic disorder. Further studies showed that NCA patients with panic disorder were more disabled at 3.5-year follow-up, had more relatives with panic disorder, were more likely to suffer from major depression, and were more likely to respond to 35% CO2 challenge with panic symptoms. Because panic disorder is highly disabling but responds well to psychological and pharmacologic treatments, screening NCA patients in the cardiology population for this disorder is recommended. PMID- 1895812 TI - Unexplained chest pain and breathlessness. AB - Complaints of chest pain and breathlessness are common in both primary care and medical outpatient settings. A subgroup of these patients who find their way into tertiary care settings and subsequently are found to have no relevant organic pathology are at risk of continuing morbidity. One possible reason for this is that diagnostic strategies often focus on establishing an organic cause of pain and ignore psychosocial factors. In this article I have attempted to describe not only the prevalence but also the clinical characteristics of patients with medically unexplained cardiorespiratory symptoms. A method of establishing a positive diagnosis of noncardiac chest pain has also been outlined. This is based on an interactive and overlapping model that takes into account not only a number of psychological and social factors but also current physical and cardiac risk factors. It is important for nonpsychiatric physicians to diagnose noncardiac pain at an earlier stage in the evolution of the disorder. This would have major beneficial effects for patients, including (1) fewer unnecessary investigations; (2) less distress and functional disability; (3) reduced cost to the hospital; and (4) fewer iatrogenic complications. PMID- 1895813 TI - Psychiatric aspects of chest pain in the emergency department. AB - We estimate that a third of the patients who present to the ED with chest pain have a current psychiatric disorder and that psychiatric disorders among chest pain patients are associated with a high rate of ED utilization for chest pain evaluations. Physicians in the ED recognize only a small fraction of the psychiatric disorders, so appropriate treatment or referral may be infrequent. The proportion of chest pain patients with CAD who also have a psychiatric disorder may be in the range of 20% to 30%, justifying careful assessment of psychiatric disorders in CAD patients. We conclude that the psychiatric aspects of chest pain are sufficiently prevalent, clinically significant, and a contributor to unnecessarily high utilization of medical services. We call for clinical research to address these questions by outlining three areas of study that will advance our knowledge and care of the patient with chest pain. PMID- 1895814 TI - Pain threshold levels and coping strategies among patients who have chest pain and normal coronary arteries. AB - Patients with noncardiac chest pain (NCCP) tend to show lower pain threshold levels for esophageal balloon distention than do patients with other painful gastrointestinal disorders and healthy controls. The NCCP patients also report greater usage of negative pain-coping strategies, less ability to perform specific behaviors to decrease pain, and higher levels of clinical pain than do other patient and healthy control groups. Behavioral treatments produce significant decreases in pain and disruption of daily activities. Further effort is needed, however, to develop treatments for NCCP that are based on knowledge of the behavioral manifestations of this disorder and the afferent mechanisms involved in perception of visceral pain. PMID- 1895815 TI - Practical approach to the diagnosis of unexplained chest pain. AB - Chest pain is a frequent medical problem causing concern for both patients and physicians. A multidisciplinary meeting recently developed algorithms for evaluating these patients in the two most common scenarios for the presentation of chest pain: (1) new onset of chest pain in the primary care setting, and (2) recurrent chest pain in the the referral setting. In both situations, the primary care physician, rather than specialists, should direct the evaluation and treatment of patients with chest pain and normal coronary angiograms. PMID- 1895816 TI - Unexplained chest pain. Future directions for research. PMID- 1895817 TI - [General practitioners or pediatricians at the child care centers?]. PMID- 1895818 TI - [New hospital organization]. PMID- 1895819 TI - [Dialysis times and mortality--are the Swedish patients insufficiently dialysed?]. PMID- 1895820 TI - [To measure glomerular filtration with iohexol and HPLC--simple, cheap, exact and flexible]. PMID- 1895821 TI - [Preoperative HIV-screening is not meaningful]. PMID- 1895822 TI - [Tendentious interviews give twisted results]. PMID- 1895823 TI - [The relation between oxygen transport and consumption can be upset in intensive care patients]. PMID- 1895824 TI - [Unacceptable long waiting for bypass surgery is frequent. Continuous development of coronary surgery is necessary]. PMID- 1895825 TI - [No considerable risks in elective surgery in patients over 90 years of age]. PMID- 1895826 TI - [Increased knowledge of dopamine receptors results in better drugs in the treatment of neurologic and psychological disorders]. PMID- 1895827 TI - [A new drug effective in gallstone pain may disguise other severe abdominal disorders]. PMID- 1895829 TI - [The Berzelius symposium on cancer screening: mammography should be focused on women aged 50 to 69 years]. PMID- 1895828 TI - [Does clomipramine in combination with alcohol provoke violent crimes?]. PMID- 1895830 TI - [Can vision defects among artists influence their art?]. PMID- 1895831 TI - [Balance in dealing with involuntarily childless persons: point to the facts of life without taking away hope]. PMID- 1895832 TI - [10-year statistics from a health care district: primary health care relieved the pressure on county health care]. PMID- 1895833 TI - [Medical prioritization instead of rationing]. PMID- 1895834 TI - [Erythropoietin is highly effective in renal anemia but should be prescribed with caution]. PMID- 1895835 TI - [Aminoglycosides--is the once-daily dosage a recommendation made after several studies?]. PMID- 1895836 TI - [Complications caused by epidural catheters--perhaps more frequent after all?]. PMID- 1895837 TI - [Over-confidence in the old-fashioned treatment of syphilis]. PMID- 1895838 TI - [Treatment of malignant diseases: how shall new methods be tested?]. PMID- 1895839 TI - [A new Swedish standard for medical gas couplings]. PMID- 1895840 TI - [Duplex ultrasound is a good method for control of infrainguinal bypass grafts]. PMID- 1895841 TI - [Hyponatremia caused severe neurologic symptoms]. PMID- 1895842 TI - [Withholding treatment]. PMID- 1895843 TI - [CK-MB is sufficient as a specific marker in the diagnosis of myocardial infarction]. PMID- 1895844 TI - [The Board of Drug Control on the treatment of asthma. Recommendations are being discussed]. PMID- 1895846 TI - Variable histotoxicity of histoacryl when used in a subcutaneous site: an experimental study. AB - Histoacryl (butyl-2-cyanoacrylate) is one of the least histotoxic cyanoacrylate derivatives and is used as a tissue adhesive. Clinical applications primarily include skin closure (blepharoplasty incisions, etc.). In a recent study, we demonstrated that Histoacryl elicits minimal histotoxicity when used to glue bone grafts to rabbit-ear cartilage. Acute inflammation was limited to areas where Histoacryl escaped from between the bone graft and ear cartilage to contact well vascularized soft tissue. In this study, Histoacryl was applied between bone graft and cartilage in one rabbit ear and adjacent to well-vascularized soft tissue with no graft in the opposite ear. Histologic analysis revealed minimal if any inflammation when small amounts of glue was used in the nonvascular region between bone graft and cartilage. However, subcutaneous implantation contacting well-vascularized soft tissue resulted in increased acute inflammation and prolonged foreign-body giant-cell response. Further studies are required to rule out any long-term problems associated with subcutaneous implantation of Histoacryl. PMID- 1895847 TI - Autologous fat injection for vocal cord medialization in the canine larynx. AB - This study examined the use of autologous fat as an alternative to Teflon and collagen as the implantable material in vocal cord medialization. Five animals underwent left recurrent laryngeal nerve sections with subsequent fat harvest and implantation into the left true vocal cords. Three animals were killed after 48 hours and 2 after 3 weeks; their larynges were examined with light microscopy. The results of the 48-hour samples show mode-rate acute inflammation and few areas of focal necrosis. The 3-week samples show no necrotic foci, minimal foreign-body reaction, and maintenance of structure and volume of the injected fat. Autologous fat may prove to be a valuable alternative to nonautologous injectable material in vocal cord augmentation. PMID- 1895845 TI - [Unexpected telephone call informed about malignant melanoma]. PMID- 1895848 TI - Fatal and other major complications of endoscopic sinus surgery. AB - Endoscopic sinus surgery has become an acceptable technique for the treatment of chronic sinus disease. This report analyzes five complications which came to my attention. Two cases were orbital:1 bilateral blindness due to damage of the optic nerves, and 1 damage of medial rectus muscle. The other 3 cases were intracranial:two cribriform plate damage with frontal lobe injury and hematoma, and 1 damage of the anterior cerebral artery, resulting in death. This rather novel technique, especially when used by less-experienced surgeons, has major complications similar to what has been reported with the traditional intranasal sphenoethmoidectomy. Knowledge of anatomy, good training, and meticulous surgical technique are very important. Endoscopic sinus surgery in patients with extensive pathology should be used with caution, especially if general anesthesia is selected or if excessive bleeding occurs. It would be beneficial to otolaryngologists to have previous experience in the traditional technique before adopting endoscopic sinus surgery to their armamentarium. Even then, major complications may occur in the hands of very experienced surgeons. Early recognition and proper management of these complications are of utmost importance in order to minimize disability or prevent death. PMID- 1895849 TI - Electromagnetic semi-implantable hearing device: phase I. Clinical trials. AB - Conventional hearing aids have improved significantly in recent years; however, amplification of sound within the external auditory canal creates a number of intrinsic problems, including acoustic feedback and the need for a tight ear mold to increase usable gain. Nonacoustic alternatives which could obviate these encumbrances have not become practical due to inefficient coupling (piezoelectric techniques) or unfeasible power requirements (electromagnetic techniques). Recent technical advances, however, prompted a major clinical investigation of a new electromagnetic, semi-implantable hearing device. This study presents the details of clinical phase I, in which an electromagnetic driver was coupled with a target magnet temporarily affixed onto the lateral surface of the malleus of six hearing aid users with sensorineural losses. The results indicate that the electromagnetic hearing device provides sufficient gain and output characteristics to benefit individuals with sensorineural hearing loss. Significant improvements compared to conventional hearing aids were noted in pure tone testing and, to a lesser degree, in speech discrimination. Subjective responses were quite favorable, indicating that the electromagnetic hearing device 1. produces no acoustic feedback; 2. works well in noisy environments; and 3. provides a more quiet, natural sound than patients' conventional hearing aids. These favorable results led to phase II of the project, in which patients with surgically amendable mixed hearing losses were implanted with the target magnet incorporated within a hydroxyapatite ossicular prosthesis. The results of this second-stage investigation were also encouraging and will be reported separately. PMID- 1895850 TI - Studying whole-mounted sections of the paranasal sinuses to understand the complications of endoscopic sinus surgery. AB - Endoscopic techniques for paranasal sinus surgery have allowed detailed and complete removal of sinus disease while promising minimum distress to the patient. The telescopic view of the operative field shows detail of the sinus anatomy and its disease, not possible in earlier transnasal techniques. Several articles document the serious complications seen with the endoscopic surgery. To understand the paranasal sinuses and their relationships to the orbit and cribriform plate, blocks of cadaver heads that included the orbit and paranasal sinuses were whole sectioned. It has been possible to see areas of the cribriform and orbital wall that are at risk to produce cerebrospinal fluid rhinorrhea and orbital complications. At the same time, landmarks for avoiding these complications can be defined to guide the surgeon during this dissection as seen through the endoscope. PMID- 1895851 TI - The intranasal ethmoidectomy: an experience with 1,077 procedures. AB - A series of 1,077 intranasal ethmoidectomies (825 with sphenoid sinusotomies) was performed in 600 patients over a 15-year period at The Mount Sinai Medical Center. The technique is a modification of the classical operation originally proposed by Yankauer. The rate of significant complications was 1.1%. A subset of 90 patients underwent 166 procedures and were followed an average of 3.5 years. The patients were analyzed according to whether the disease was focal or diffuse, infectious or polypoid, and whether asthma was present. The surgical success rate was 88% in nonasthmatics, but dropped to 50% in asthmatic patients despite total sphenoethmoidectomy. This underscores the importance of this condition as a biological modifier of surgical prognosis. Accordingly, a system of classification of sinus diseases is proposed based upon disease extent and type and whether asthma is present. PMID- 1895852 TI - Long-term results after lateral cranial base surgery. AB - The surgical management of patients with slow-growing benign temporal bone neoplasms has been criticized because of its significant morbidity and mortality compared with results after radiation therapy, but long-term control by irradiation remains unproved. Long-term surgical results have not been studied previously. One hundred twenty-nine skull base operations were performed in 126 patients at the Otology Group, Nashville, Tenn., from January 1970 through May 1987. Fifty-eight patients responded to questionnaires focusing on recovery from loss of cranial nerves. All patients regained some degree of facial function (class V or better), no alimentary tubes or tracheotomies were in use, and no patients had debilitating aspiration. Long-term compensation from the cranial nerve deficits of lateral skull base surgery can be expected in most patients and should not be used as an argument for irradiation in patients with a long life expectancy at time of diagnosis. PMID- 1895853 TI - Auditory performance with simultaneous intracochlear multichannel stimulation. AB - Different sound processing strategies are used in the various cochlear implant designs. This report presents auditory data on 35 patients implanted at the University of Utah from April 1984 to April 1989. A multichannel monopolar electrode system is inserted intracochlearly. During daily use and auditory performance testing, four electrodes receive simultaneous input. The incoming acoustic signal is amplified and routed to the different electrodes through a band-pass filter system. Mean pure-tone performances were: 500 Hz-29.6 +/- 9.4 dB; 1000 Hz-23.5 +/- 13.2 dB; 2000 Hz-25.4 +/- 9.6 dB; 4000 Hz-32.1 +/- 11.5 dB; and 6000 Hz-42.2 +/- 7.7 dB. Audio-only CID sentence testing showed 51.4% of patients scoring better than 60% and 40% scoring better than 80%. The percutaneous pedestal is well tolerated; patients have had the systems in place for 13 and 15 years. PMID- 1895854 TI - Update: ansa cervicalis to recurrent laryngeal nerve anastomosis for unilateral laryngeal paralysis. AB - Twenty cases of unilateral laryngeal paralysis are reported. Satisfactory follow up intervals and data (videostroboscopy and glottographic analysis) were available on 12 patients. The excellent to normal phonatory quality achieved in many of these patients indicates that the ansa cervicalis to recurrent laryngeal nerve anastomosis is the procedure of choice in selected patients with unilateral vocal cord paralysis. Excellent medialization of the paralyzed cord, as well as correction of arytenoid malposition and thyroarytenoid muscle atrophy appear to explain the technique's success, since the reinnervated cord neither abducts nor adducts. We feel that this technique is the procedure of choice in younger patients, or those who use their voices professionally, since the phonatory quality achieved is superior to Teflon injection or Isshiki thyroplasty, and the technique is reversible. PMID- 1895855 TI - The use of absorbable sutures in laser-assisted microvascular anastomoses. AB - The efficacy of the laser in performing microvascular anastomoses has been well established in the laboratory using a number of wavelengths. These studies have concluded that laser-assisted microvascular anastomoses are at least comparable to, if not superior to, ordinary suture techniques. The advantages have been the diminished foreign body reaction that occurs as a consequence of using only a few stay sutures to hold the vessels in approximation while the laser bonding is performed, as well as the rapidity of the surgery. We have already shown that absorbable sutures (polyglactin 910) are as efficacious as standard nonabsorbable sutures (nylon) in both arterial and venous microanastomoses. The current study was undertaken to see if the foreign body reaction could be diminished even further by the use of absorbable 10.0 sutures and compare these findings to laser assisted microvascular anastomoses performed with nonabsorbable sutures. The carbon dioxide milliwatt laser was used to perform laser-assisted microvascular anastomoses in rat femoral arteries and veins. Patency rates and histological response were compared at intervals of 3 days and 1, 2, 4, 8, and 12 weeks postoperatively. Both arterial and venous patency rates were comparable (overall absorbable, 91.2%-52/57; overall nonabsorbable, 87.7%-50/57), as was the degree of inflammation and fibrosis. We conclude that absorbable sutures can be used for laser-assisted microvascular anastomoses and have the potential of allowing healing to occur without any foreign material within the surgical site. PMID- 1895856 TI - Bone-inducing implants in head and neck surgery: an experimental study. AB - The use of autologous bone for head and neck reconstruction requires a separate harvesting procedure which provides limited quantities of bone that may become infected or undergo resorption after being implanted. In this study, a collagen/ceramic carrier containing osteoinductive factor extract (OFE) was used in a rabbit facial augmentation model. Bone-inducing activity of these implants were evaluated in subcutaneous, intramuscular, and subperiosteal sites. Implants with (test) and without OFE (control) were placed on opposite sides of the face in 40 rabbits, and were harvested at 21 days. Bone formation was evaluated by implant alkaline phosphatase determinations and histomorphometry. Osteoblastic activity, bone formation, and preservation of facial augmentation were noted in the OFE implants, showing maximal bone formation when implanted subperiosteally. Control (no OFE) and demineralized bone implants showed no bone formation. Before these implants can be used clinically, novel bone-inducing factors must be manufactured by recombinant deoxyribonucleic acid (DNA) methodology to verify activity of the homogeneous molecule which would be free of other proteins or infectious agents. PMID- 1895857 TI - Iodine-125 seed implantation as an adjunct to surgery in advanced recurrent squamous cell cancer of the head and neck. AB - Survival for extensive recurrent squamous cell carcinomas of the head and neck remains poor, with the major cause of death being local recurrence. Surgical implantation of iodine-125 interstitial seeds allows tumoricidal doses of radiation to be delivered to residual tumor while minimizing radiation doses to the surrounding tissues. From 1978 to 1988, 39 implantations were performed on 35 patients for extensive recurrent squamous cell carcinoma of the head and neck. The decision for implantation was based on positive margins or close to resection margins from frozen sections after salvage resection. The determinate 5-year disease-free survival was 41%, with both the overall and no evidence of disease 5 year survivals being 29%. Significant complications occurred in 36% of all cases. This figure increased to 56% when flap reconstruction was required. Possible reasons for this seemingly high complication rate are discussed. Considering the advanced nature of these recurrent carcinomas, surgical resection with iodine-125 seed implantation appears to be an effective method of managing disease that might otherwise be judged unresectable and treated for palliation only. PMID- 1895858 TI - Patency rate of endoscopic middle meatus antrostomy. AB - A series of 145 patients with chronic sinusitis were treated with functional endoscopic sinus surgery. Patency of the middle meatus was evaluated by actuarial life-table methods. After 24 months' follow-up, the overall patency rate of endoscopic middle meatotomy was 94.08%. Questionnaire data indicated that 91.8% of these patients were improved or asymptomatic. This preliminary study indicates that the patency rate of middle meatal antrostomy appears to be greater than that of inferior meatal antrostomy when compared to literature controls, and that a high percentage of these patients are improved by this surgery. PMID- 1895859 TI - Squamous cell carcinoma of the upper aerodigestive tract associated with well differentiated carcinoma of the thyroid gland. AB - The association of squamous cell carcinoma of the upper aerodigestive tract with well-differentiated thyroid carcinomas has rarely been reported in the literature. We report 10 cases illustrating this occurrence. In eight cases, the thyroid carcinoma was discovered accidentally on histological examination of a single neck node, a neck node dissection specimen, an unexpectedly found thyroid nodule, or a systematically resected thyroid lobe, all during surgical treatment of an upper aerodigestive tract carcinoma. In the other two cases, metastatic thyroid neck nodes appeared during the follow-up of a patient with an upper aerodigestive tract carcinoma. No case of upper aerodigestive tract carcinomas was found during the follow-up of thyroid cancer patients. In most cases, adequate thyroid cancer surgery was performed simultaneously or later. Prognosis was essentially determined by the upper aerodigestive tract cancer. PMID- 1895860 TI - Vocal quality of decannulated children following laryngeal reconstruction. AB - Laryngotracheal reconstruction with expansion surgery is a reliable method for treatment of laryngotracheal stenosis in children. It allows for decannulation of the patient and restoration of vocal communication. Previous information regarding vocal quality in these patients has been scant. Sixteen children who underwent successful laryngotracheal reconstruction were evaluated using a standardized voice assessment during each of the following: phoneme prolongation, counting, storytelling, and spontaneous conversation. Interjudge ratings were obtained to establish reliability. The location and severity of the laryngotracheal stenosis and the method of treatment were reviewed. Twelve children have a functional voice compared to six preoperatively. Overall, vocal parameters suggested a particular pattern consisting of a lower than optimal pitch and a restricted pitch range. Laryngotracheal reconstruction does make oral communication possible for children who would otherwise have persistent tracheotomy. However, vocal quality appears to be disturbed in most of the patients. PMID- 1895861 TI - Facial reanimation: the temporalis muscle and middle fossa surgery. PMID- 1895862 TI - Ossicular chain reconstruction: a combined prosthesis with organic and synthetic material. AB - The surgical techniques to restore the sound pressure transfer mechanism in surgery of chronic otitis media are still in an evolutionary stage. Ossicular interposition is effective and certainly is not controversial. The use of various organic prostheses has been criticized. The prosthesis with a shaft of Teflon and a homograft bone flange is an alternative method which has been successful in our hands. PMID- 1895863 TI - The location of the maxillary Os and its importance to the endoscopic sinus surgeon. PMID- 1895864 TI - The otolaryngologic manifestations of gastroesophageal reflux disease (GERD): a clinical investigation of 225 patients using ambulatory 24-hour pH monitoring and an experimental investigation of the role of acid and pepsin in the development of laryngeal injury. AB - Occult (silent) gastroesophageal reflux disease (GER, GERD) is believed to be an important etiologic factor in the development of many inflammatory and neoplastic disorders of the upper aerodigestive tract. In order ot test this hypothesis, a human study and an animal study were performed. The human study consisted primarily of applying a new diagnostic technique (double-probe pH monitoring) to a population of otolaryngology patients with GERD to determine the incidence of overt and occult GERD. The animal study consisted of experiments to evaluate the potential damaging effects of intermittent GER on the larynx. Two hundred twenty five consecutive patients with otolaryngologic disorders having suspected GERD evaluated from 1985 through 1988 are reported. Ambulatory 24-hour intraesophageal pH monitoring was performed in 197; of those, 81% underwent double-probe pH monitoring, with the second pH probe being placed in the hypopharynx at the laryngeal inlet. Seventy percent of the patients also underwent barium esophagography with videofluoroscopy. The patient population was divided into seven diagnostic subgroups: carcinoma of the larynx (n = 31), laryngeal and tracheal stenosis (n = 33), reflux laryngitis (n = 61), globus pharyngeus (n = 27), dysphagia (n = 25), chronic cough (n = 30), and a group with miscellaneous disorders (n = 18). The most common symptoms were hoarseness (71%), cough (51%), globus (47%), and throat clearing (42%). Only 43% of the patients had gastrointestinal symptoms (heartburn or acid regurgitation). Thus, by traditional symptomatology, GER was occult or silent in the majority of the study population. Twenty-eight patients (12%) refused or could not tolerate pH monitoring. Of the patients undergoing diagnostic pH monitoring, 62% had abnormal esophageal pH studies, and 30% demonstrated reflux into the pharynx. The results of diagnostic pH monitoring for each of the subgroups were as follows (percentage with abnormal studies): carcinoma (71%), stenosis (78%), reflux laryngitis (60%), globus (58%), dysphagia (45%), chronic cough (52%), and miscellaneous (13%). The highest yield of abnormal pharyngeal reflux was in the carcinoma group and the stenosis group (58% and 56%, respectively). By comparison, the diagnostic barium esophagogram with videofluoroscopy was frequently negative. The results were as follows: esophagitis (18%), reflux (9%), esophageal dysmotility (12%), and stricture (3%). All of the study patients were treated with antireflux therapy. Follow-up was available on 68% of the patients and the mean follow-up period was 11.6 +/- 12.7 months.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1895865 TI - Optical properties of human sclera, and their consequences for transscleral laser applications. AB - The spectral dependence of the optical properties of human sclera adjacent to the limbus was investigated and related to the potentials of transscleral photocoagulation. The total transmission, absorption, and reflection, as well as the angular distribution of the transmitted and reflected light were measured at five laser wavelengths (442 nm, 514 nm, 633 nm, 804 nm, and 1,064 nm), both for noncontact and contact applications. Absorption and scattering coefficients were determined using the Kubelka-Munk model for light propagation through a scattering tissue. The scleral transmission is only 6% at 442 nm but increases to 35% at 804 nm and to 53% at 1,064 nm. The absorption is high at short wavelengths with 40% at 442 nm but it is only 6% at 804 nm and 1,064 nm. The reflection is generally higher than 40% and shows little wavelength dependence. The transmitted light is scattered diffusely at short wavelengths, but at 804 nm and 1,064 nm it exhibits a fairly narrow angular distribution in forward direction. Fiber contact leads to an increase of transmission, with a factor of 3.5 at 442 nm, of 2.0 at 804 nm, and 1.5 at 1,064 nm. Our results indicate that the diode laser (804 nm) and the Nd:YAG laser (1,064 nm) with contact delivery are best suited for transscleral photocoagulation. PMID- 1895866 TI - Contact diode laser application through a fiberoptic cutting tip. AB - We applied diode laser energy through a fiberoptic probe to cut ocular structures. The diameter of the probe's tip was 100 microns. The amount of energy used for cutting the lid, the cornea, or for perforation of the glove was 2.5 watts in the continuous mode. The incised border demonstrated coagulation into the healthy tissue ranging from 10 to 50 microns. PMID- 1895867 TI - Nd:YAG laser-induced hyperthermia treatment of spontaneously occurring veterinary head and neck tumors. AB - Conventional hyperthermia treatment of superficial tumors in the oral cavity is troublesome due to difficulty in accessing the lesion. A new hyperthermia technique employing near-infrared radiation delivered through a flexible silica optical fiber is described. The system consisted of an Nd:YAG laser for tissue heating, a He-Ne laser for aiming beam, a computer-controlled optical shutter, an interstitial thermometer, computer, and a printer. A 3-m-long 600-microns silica fiber delivered laser energy to the tumor via surface illumination. Using the aiming beam, the spot size was adjusted to include 5 mm of surrounding normal tissue. A thermocouple implanted in the tumor base provided temperature feedback to maintain desired hyperthermic temperature within the lesion. Three spontaneously occurring canine (two squamous cell carcinomas on the gum, one pigmented melanoma on the hard palate) and one feline tumor (squamous cell carcinoma on the nose) have been treated with Nd:YAG laser hyperthermia. Hyperthermia was delivered at 43.5 degrees C for 1 h. All animals received standard radiation treatment prior to hyperthermia. Nd:YAG laser hyperthermia allowed effective and efficient delivery of heat to veterinary nasal and oral lesions otherwise not treatable with conventional heating techniques. PMID- 1895868 TI - Experimental treatment of thrombotic vascular occlusion. AB - The role of laser energy in the treatment of thrombotic vascular occlusion was evaluated in two sets of experiments. First, 10 polytetrafluoroethylene grafts were used to replace segments of the superficial femoral arteries in dogs and were thrombosed by distal ligation. Occlusion was maintained for one hour, or for 7, 14, 21, and 28 days in each of two grafts. Patency was restored in all 10 grafts without perforation or anastomotic disruption using a 2 mm hot tip probe powered by an Argon laser. However, increased organization of thrombus related to the duration of occlusion lead to decreased laser channel diameters, and 75% of the 28 day thrombus remained in the graft after recanalization. The second experiments tested the added benefit of thrombolytic infusion following laser recanalization. Bilateral external iliac artery thrombosis was induced in dogs by operative vessel isolation, de-endothelialization, and thrombin injection. At 7 days the efficacy of laser-assisted thrombolysis (LAT) versus enzymatic thrombolysis (ET) alone was compared. Eight vessels underwent ET by urokinase (4000 I.U./min.); 14 vessels were laser recanalized prior to thrombolytic infusion. LAT was performed from a carotid artery approach in 8 vessels (antegrade) and from a femoral artery in 6 vessels (retrograde). In contrast to studies using the hot tip alone, both ET and LAT accomplished complete thrombus removal. However, LAT lead to significant iliac arterial flow in 9 +/- 8 min. (antegrade) and 25 +/- 8 min. (retrograde) while ET required 109 +/- 47 min (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1895869 TI - Argon laser therapy for perianal Bowen's disease: a case report. AB - Bowen's disease (intraepithelial squamous cell carcinoma) may occasionally occur in anal canal or perianal region. Surgical excision in this area may result in significant complications and a recurrence rate of 9-19%. A case of successful treatment of anal and perianal Bowen's disease using argon laser therapy is presented. No acute or chronic complications resulted from laser therapy. Twenty eight months after the initial diagnosis the patient is disease free. Laser therapy also provides the potential for repeated treatment of recurrent lesions without significant patient discomfort or inconvenience. Argon laser therapy should be considered as a therapeutic option in the treatment of Bowen's disease. PMID- 1895870 TI - Direct determination of homovanillic acid release from the human brain, an indicator of central dopaminergic activity. AB - The plasma concentration of the dopamine (DA) metabolite, homovanillic acid (HVA), is used as an indicator of central nervous system dopaminergic activity. Using percutaneously inserted catheters we were able to obtain blood samples simultaneously from the right and left internal jugular veins. Veno-arterial HVA plasma concentration differences combined with adjusted organ plasma flows were used, according to the Fick Principle, to determine the HVA overflow from the brain. The HVA overflow from the liver was also measured. HVA overflow from the brain represented 12% of the total body HVA production. A similar amount was released from the liver, illustrating the limited validity of peripheral plasma HVA measurements as an indicator of central dopaminergic activity. HVA release from the human brain displayed a degree of asymmetry, the overflow into the left internal jugular vein being 36% greater than that into the right. Cerebral venous blood flow scans indicated that cortical cerebral regions drained preferentially into the right internal jugular; by inference the higher HVA overflow on the left originated from dopamine-rich subcortical brain areas. Since HVA in plasma may arise from the metabolism of DA existing either as a neurotransmitter or a norepinephrine (NE) precursor we measured the internal jugular vein plasma concentrations of NE, and its metabolite dihydroxyphenylglycol (DHPG), to determine whether they displayed a similar pattern of release to HVA. The overflow of both NE and DHPG into the right internal jugular vein was approximately double that on the left. Since the overflow of HVA did not parallel that of NE and DHPG it may be inferred that the origin of much of the subcortically produced HVA is from dopaminergic neurons and not from the metabolism of precursor DA in noradrenergic neurones or cerebrovascular sympathetic nerves. PMID- 1895872 TI - Detection and characterization of extracellular phospholipase A2 in pleural effusion of patients with tuberculosis. AB - Extracellular phospholipase A2 activity has been identified in pleural fluid of patients with tuberculosis. This enzyme is a calcium requiring protein and has a pH optimum of 10.0. The enzyme was inhibited by the active site-directed histidine reagent, rho-bromophenacyl bromide. Ionic and non-ionic detergents, or the sulfhydryl reagent dithiothreitol, caused loss of enzyme activity. When substrate specificity was tested using 2-[1-14C]linoleoyl phospholipids as substrates, phosphatidyl-ethanolamine was the best substrate, followed by phosphatidylserine and phosphatidylcholine. This phospholipase A2 showed high affinity for heparin, and was recognized by a monoclonal antibody raised against phospholipase A2 from human synovial fluid. These findings suggest that an extracellular phospholipase A2, which may belong to the 14K group II phospholipase A2 family, exists in the pleural fluid of patients with tuberculosis. PMID- 1895871 TI - Activated neutrophils inhibit cerebrovascular endothelium-dependent relaxations in vitro. AB - The effect of formyl-Met-Leu-Phe- (fMLP-) activated feline neutrophil granulocytes on endothelium-dependent and independent relaxations was studied in the middle cerebral artery of the cat in vitro. Endothelium-dependent relaxations caused by acetylcholine and ATP were markedly inhibited after 30 minutes of incubation of the vessels with neutrophils (5000 cells/microliter) in the presence of 5 microM fMLP, followed by a replacement of the bath solution in order to remove the neutrophils from the medium. Direct vasorelaxations in response to the nitric oxide donor compound SIN-1, however, remained unchanged. Both neutrophils and fMLP caused transient contractions during the incubation period. The present study provides direct evidence for the ability of activated neutrophils to cause an inhibition of vascular endothelium-dependent responses in vitro. PMID- 1895873 TI - Cycloheximide blocks the fall of plasma and tissue tryptophan levels after tryptophan-free amino acid mixtures. AB - The hypothesis that incorporation of tryptophan (TRY) into proteins is the mechanism underlying the decrease in plasma and tissue TRY levels after a TRY free amino acid mixture was investigated. Rats fasted 15 hours were pretreated with saline or with the protein synthesis inhibitor cycloheximide (CHEX) and treated with saline or a TRY-free amino acid mixture. In a first experiment, in saline pretreated rats the TRY-free mixture caused a decrease of 49% in total plasma TRY, of 64% in free plasma TRY, of 66% in brain TRY and of 42% in liver TRY. After 5 mg/kg of CHEX the same TRY-free diet caused a decrease of 5% in total plasma TRY, 14% in free plasma TRY, 18% in brain TRY and 9% in liver TRY. In a second experiment, the TRY-free diet caused a 43% decrease of total plasma TRY in saline pretreated animals and a decrease of 15%, 6% and 2% respectively after the pretreatment with 0.3, 1.0 and 5.0 mg/kg of CHEX. In brain TRY, the TRY free diet caused a 62% decrease in saline pretreated rats and a decrease of 38%, 20% and 19% respectively after the pretreatment with 0.3, 1.0 and 5.0 mg/kg of CHEX. Since 5.0 mg/kg of CHEX almost completely block protein synthesis and since doses of CHEX from 0.3 to 5.0 mg/kg cause a dose-dependent inhibition of protein synthesis, our data support the hypothesis that protein synthesis is the mechanism through which TRY-free mixtures decrease TRY levels. PMID- 1895874 TI - Lead acetate delays rapid postnatal mouse brain and body growth. AB - Starting at parturition and continuing until weaning, mothers of five mouse litters received tap water while five others had 10 mg PbAc/ml in their drinking water. The offspring receiving lead from the mothers had significantly lower body weights after the first days of receiving lead; their slowed body growth led to a 2-day delay of onset (usually at 16-18 days) of their last rapid body growth stage. They also had significantly smaller brain weights between age 14 days and weaning (23 days). The onset of rapid brain growth was delayed from its usual onset at 16-18 days to about 22-23 days before rising to about the same value as the control mice at 26 days. Thus, the initial effect on brain growth is decidedly greater than on body growth, though brain weight later reaches close to the control value. PMID- 1895875 TI - Infection of cultured human airway epithelial cells by influenza A virus. AB - The lack of an adequate in vitro model has hampered study of the cellular basis by which influenza A virus causes disease in the human airway. We report in vitro infection of human airway epithelial cells by influenza A virus. Fetal and adult human tracheal and bronchial epithelial cells cultured from explants and SV40 transformed adult human tracheal epithelial cells were exposed to a recently isolated strain of influenza A virus (H1N1) and a laboratory passaged strain (WSN) of influenza A virus at similar multiplicity of infection. All cultures derived from explants showed hemadsorption (approximately 30% of the cells) with the H1N1 virus. No hemadsorption was detected with the WSN virus. One of two transformed cell lines showed a 5-10% hemadsorption to cells after H1N1 exposure and none following exposure to WSN. Immunofluorescent staining for influenza A specific antigens in virus-exposed, explant-derived cells indicated viral infection and replication in these cells. Hemagglutinating material in the growth medium of infected, explant-derived cell lines, increased as a function of time, indicating the production of virus proteins. Exposure of rhesus monkey kidney cells and new human tracheal epithelial cultures to supernatant from these cells resulted in hemadsorption, indicating the presence of infectious virus in the supernatant. Light microscopic examination of virally infected bronchial epithelial cells demonstrated that the common types of cytopathic changes were rarely seen while cell proliferation continued over time. The data indicate that influenza A virus can infect, replicate, and produce infectious virus in cultured human tracheal and bronchial epithelial cells. PMID- 1895876 TI - Reciprocal changes of plasma glucose and ketone bodies in fasted and acutely diabetic rats after CNS stimulation. AB - To assess the effect of chemical stimulation of the central nervous system (CNS) on ketogenesis, we injected neostigmine (5 x 10(-8)mol) into the third cerebral ventricle in normal rats fasted for 48 h and fed rats with diabetes induced by streptozotocin (STZ, 80 mg/kg). The hepatic venous plasma levels of ketone bodies (3-hydroxybutyrate and acetoacetate), free fatty acids (FFA), and glucose were measured for 120 min after the injection of neostigmine under pentobarbital anesthesia. In the normal rats, plasma glucose levels were significantly increased but neither ketone bodies nor FFA were affected by CNS stimulation with neostigmine. In contrast the plasma levels of ketone bodies and FFA were significantly increased in STZ-diabetic rats, while glucose levels remained unchanged. The intravenous infusion of somatostatin (1.0 microgram/kg/min) suppressed the increase in plasma ketone bodies following CNS stimulation in STZ diabetic rats. These findings suggest that CNS stimulation with neostigmine may accelerate ketogenesis by promoting the lipolysis, which may be induced by glucagon, in fed diabetic rats but not in normal fasted rats. PMID- 1895877 TI - Plasma lipoproteins and liver lipids in two breeds of geese with different susceptibility to hepatic steatosis: changes induced by development and force feeding. AB - Susceptibility to fatty liver in the force-fed goose is partly under genetic control. However, the mechanisms leading to liver steatosis in this avian model are poorly understood, but may involve perturbation in hepatic lipoprotein synthesis. Plasma lipoproteins were fractionated by density gradient ultracentrifugation from plasma of geese differing in their susceptibility to liver steatosis (Landes breed, highly susceptible; Rhine breed, partly resistant). The concentrations and chemical compositions of the major lipoprotein classes (VLDL, IDL, LDL and HDL) were characterized at 8, 22 and 27 wk of age and compared to the lipid composition of the corresponding liver. In non-force-fed geese, the lipoprotein profile was typical of birds, with high-density lipoprotein (HDL) predominating (4-5 g/L). However, at 22 and 27 wk of age, very low-density lipoprotein (VLDL) levels were significantly lower in Landes geese suggesting that this breed may possess a lower ability to export liver lipids, which would explain its susceptibility to liver steatosis when overfed. The livers of force-fed geese were specifically enriched in triglyceride, and to a lesser extent, in cholesteryl esters and non-esterified fatty acids as compared to those of control geese of the same age (27 wk). This accumulation of lipids was more pronounced in the Landes breed and was responsible for the higher liver weight in that breed. In both breeds, liver steatosis was accompanied by an increase in plasma levels of HDL (11 g/L), whereas low-density lipoproteins were essentially absent.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1895878 TI - The hypercholesterolemic effect of dietary coconut fat versus corn oil in hypo- or hyperresponsive rabbits is not exerted through influencing cholesterol absorption. AB - In two inbred strains of rabbits with high or low response of plasma cholesterol to dietary saturated versus polyunsaturated fatty acids, the efficiency of intestinal cholesterol absorption was measured. The feeding of a cholesterol-free purified diet containing saturated fatty acids in the form of coconut fat, when compared with a diet containing corn oil as polyunsaturated fatty acids, did not influence the efficiency of cholesterol absorption in the two rabbit strains. Irrespective of the dietary fat source, the hyperresponsive rabbits absorbed cholesterol more efficiently. It is concluded that the hypercholesterolemic effect of dietary coconut fat versus corn oil is not exerted by influencing cholesterol absorption. PMID- 1895879 TI - Protective effect of vitamin E on linoleic acid hydroperoxide-induced injury to human endothelial cells. AB - The protective effects of vitamin E (alpha-tocopherol) and its model compounds, which act as antioxidants, on linoleic acid hydroperoxide-induced injury to human umbilical vein endothelial cells were examined. When incubated at 50 microM with endothelial cells at 37 degrees C for 24 hr, alpha-tocopherol protected the cells from injury, and 2,2,5,7,8-pentamethylchroman-6-ol showed a similar protective effect. Trolox C, a water-soluble vitamin E model compound, had no protective effect. Tocol, a poor antioxidant, proved toxic. During preincubation, alpha tocopherol was incorporated into the cells at 16.6 nmol/mg protein, while the pentamethylchromanol was incorporated at 0.5 nmol/mg protein; Trolox C was not incorporated at all. The results suggest that agents having both high antioxidant activity and lipophilicity can protect endothelial cells from linoleic acid hydroperoxide-induced injury. PMID- 1895880 TI - Age-related changes in the metabolism of cholesterol in rat liver microsomes. AB - The effects of aging on the hepatic metabolism of cholesterol were studied in 1-, 6- and 24-month-old male Sprague-Dawley rats. Microsomal 3-hydroxy-3 methylglutaryl coenzyme A (HMG-CoA) reductase activity, which regulates cholesterol biosynthesis, decreased from 835 +/- 144 (SEM) pmol/min/mg protein in the youngest group to 219 +/- 34 and 205 +/- 53 pmol/min/mg protein (p less than 0.001) in the 6- and 24-month-old groups, respectively. Cholesterol 7 alpha hydroxylase activity, which governs bile acid synthesis, was gradually reduced from 70 +/- 14 pmol/min/mg protein in the 1-month-old group to 32 +/- 7 and 16 +/ 3 pmol/min/mg protein (p less than 0.05) in the 6- and 24-month-old groups, respectively. Acyl coenzyme A:cholesterol acyltransferase activity, which catalyzes the esterification of cholesterol, averaged 431 +/- 47 and 452 +/- 48 pmol/min/mg protein in the 1- and 6-month-old groups, respectively, and was increased to 585 +/- 55 pmol/min/mg protein (p less than 0.05) in the 24-month old group. The level of total cholesterol showed an age-related increase from 1.56 +/- 0.16 mg/g liver in the 1-month-old group to 1.70 +/- 0.15 and 2.20 +/- 0.19 mg/g liver (p less than 0.05) in the 6- and 24-month-old groups, respectively. The increase was mainly caused by an accumulation of esterified cholesterol. We conclude that a marked decrease in HMG-CoA reductase occurs between 1 and 6 months of age; thereafter the enzyme activity stays unchanged. The activity of cholesterol 7 alpha-hydroxylase decreases progressively and drastically with age, whereas the capacity for esterifying cholesterol increases slightly.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1895881 TI - Omega 3 fatty acids increase spontaneous release of cytosolic components from tumor cells. AB - Mice fed menhaden (fish) oil or coconut oil-rich diets were inoculated intraperitoneally with a rapidly growing leukemia, T27A. After one week, the tumor cells were harvested, and 51Cr was used to label intracellular molecules. Spontaneous release of 51Cr was used as a measure of plasma membrane permeability. Compared to cells from mice fed coconut oil (rich in saturated fatty acids), tumor cells from mice fed menhaden oil (rich in long chain polyunsaturated omega 3 fatty acids) showed an increased level of spontaneous 51Cr release, which was exacerbated by increased temperature and reduced by extracellular protein. At physiological salt concentrations, the released 51Cr was detected in particles of approximately 2700 daltons. Enhanced permeability correlated with the incorporation of dietary (fish oil) omega 3 polyunsaturated fatty acids docosahexaenoic and eicosapentaenoic acid into the tumor cells. The results demonstrate that omega 3 fatty acids are incorporated into cellular constituents of tumor cells and change properties associated with the plasma membrane. This result suggests that dietary manipulation may be used to enhance tumor cell permeability and contribute to tumor eradication. PMID- 1895882 TI - Do rat kidney cortex microsomes possess the enzymatic machinery to desaturate and chain elongate fatty acyl-CoA derivatives? AB - Rat kidney cortex microsomal preparations were unable to catalyze delta 9, delta 6 and delta 5 desaturation of stearoyl-coenzyme A (CoA), linoleoyl-CoA and dihomo gamma-linolenoyl-CoA, respectively. The kidney cortex microsomal fraction, however, did catalyze the malonyl-CoA dependent fatty acyl-CoA elongation. The biochemical properties of palmitoyl-CoA elongation were studied as a function of protein concentration, time, reduced nicotinamide adenine dinucleotide phosphate (NADPH), malonyl-CoA and substrate concentrations; of the substrates investigated, delta 6,9,12-18:3 was the most active. Unlike what was observed in the hepatic system, a high-carbohydrate, fat-free diet did not induce kidney fatty acid chain elongation. All intermediate kidney cortex microsomal reactions, i.e., beta-ketoacyl-CoA reductase, beta-hydroxyacyl-CoA dehydrase and trans-2 enoyl-CoA reductase activities, were significantly higher (greater than one order of magnitude) than the condensing enzyme activity, suggesting that the rate limiting step in total elongation is the initial condensation reaction. Contrary to other reports, the results suggest that the kidney cannot synthesize arachidonic acid needed for eicosanoid production. PMID- 1895883 TI - Thermotropic phase properties of the hydroxyceramide/cholesterol system. AB - The interaction of cholesterol with ceramides containing alpha-hydroxy fatty acyl chains (hydroxyceramides) has been studied as a foundation for characterizing the lipid bilayers of the stratum corneum. A relatively large quantity of cerebrosides was obtained from bovine brain and converted to ceramides through removal of the carbohydrate side chain. The ceramides were separated based on the absence or presence of hydroxy fatty acyl chains. The lyophilized hydroxyceramides showed a broad melting region at 92 degrees C. Hydroxyceramides dispersed in water produced a relatively narrow, thermotropic transition at 75 degrees C. The effect of cholesterol on this thermotropic phase transition of hydroxyceramides was determined by differential scanning calorimetry. With respect to the main transition, cholesterol caused a broadening of the phase transition at relatively low levels as well as a decrease in the peak transition temperature. The presence of cholesterol at levels in excess of 7 wt% gave rise to an additional low-temperature transition at 55 degrees C. Upon immediate rescanning, this transition was exothermic, but with increasing incubation time the area under the excess heat capacity curve as a function of temperature became smaller. After two days or more, the transition observed was endothermic. At cholesterol levels between 40 and 50 wt%, multiple peaks were observed. From comparisons with related systems, the cooperative thermal transitions of hydroxyceramides with cholesterol are suggested to result from changes in hydrogen bonding or be due to phase separation. The composition of isolated brain ceramides is being compared with that reported for the stratum corneum. PMID- 1895884 TI - Lymphatic absorption of structured glycerolipids containing medium-chain fatty acids and linoleic acid, and their effect on cholesterol absorption in rats. AB - The effects of various structured triglycerides containing medium-chain (caprylic or capric acids) and long-chain (linoleic acid) fatty acids on fatty acid and cholesterol absorption were studied in lymph-cannulated rats. A considerable portion of capric and caprylic acid was absorbed through the lymph duct, although to a lesser extent than was linoleic acid. Capric and linoleic acid located at the 2-position of 2-decanoyl-1,3-dilinoleoyl-glycerol (18:2/10:0/18:2) and 2 linoleoyl-1,3-didecanoyl-glycerol (10:0/18:2/10:0), respectively, tended to be absorbed more efficiently than those located at the 1- and 3-position or those from tricaprin (10:0/10:0/10:0) or trilinolein (18:2/18:2/18:2). A similar trend was observed when the medium-chain fatty acid was caprylic acid instead of capric acid. Caprylic acid absorption from 2-octanoyl-1,3-dilinoleoyl-glycerol (18:2/8:0/18:2) was significantly greater (p less than 0.05) than from 2 linoleoyl-1,3-dioctanoyl-glycerol (8:0/18:2/8:0) or tricaprylin (8:0/8:0/8:0). Preferential absorption of caprylic and linoleic acid was not observed when the 1 to 2 and the 2 to 1 mixtures of 8:0/8:0/8:0 and 18:2/18:2/18:2, respectively, were administered. The structured lipids did not affect the lymphatic absorption of cholesterol. The results suggest that structured triglycerides composed of medium-chain fatty acids and linoleic acid may be more useful for the treatment of lipid malabsorption than are mixtures of medium-chain triglyceride (MCT) and long-chain triglyceride (LCT). PMID- 1895885 TI - Oxysterol incorporation into rat aorta resulting in elastin compositional changes. AB - The incorporation of dietary cholestan-3 beta,5 alpha,6 beta-triol (triol) into rat thoracic aortic tissue and changes in amino acid composition of the elastin were investigated to identify the cytotoxic properties of the triol. Weanling male Sprague-Dawley rats were fed the following diets for three months: (i) normal chow, (ii) normal chow with 1% (w/w) cholesterol added, or (iii) normal chow with 0.9% (w/w) cholesterol and 0.1% (w/w) triol added. Triol levels in the blood and in the thoracic aortic tissue were measured. Compositional changes of elastin were also determined. After three months on the triol-containing diet, triol was found in the thoracic aorta but was not detected in the blood. Amino acid analyses of the aortic tissue elastin revealed that the proline levels in the triol-fed animals were significantly greater than in the other two diet groups, while the elastin levels of leucine, aspartate, arginine, and phenylalanine decreased significantly. The mechanism for these observed changes induced by triol may reflect alternate splicing of elastin messenger ribonucleic acid (mRNA) resulting in structual changes in the elastin molecule. Dietary triol does contribute to tissue triol content and is associated with aortic elastin compositional changes. How these changes may contribute to the development of cardiovascular disease is not known. PMID- 1895886 TI - Effect of n-3 fatty acids on the key enzymes involved in cholesterol and triglyceride turnover in rat liver. AB - The effect of long-chain n-3 fatty acids on hepatic key enzymes of cholesterol metabolism and triglyceride biosynthesis was investigated in two rat models. In the first model, rats were intravenously infused for two weeks with a fat emulsion containing 20% of triglycerides in which either n-6 or n-3 fatty acids predominated. The treatment with n-3 fatty acids led to a reduction primarily of serum cholesterol (45%), but also of serum triglycerides (18%). HMG-CoA reductase activity and cholesterol 7 alpha-hydroxylase activity were reduced by 45% and 36%, respectively. There were no significant effects on diacylglycerol acyltransferase (DGAT) or phosphatidate phosphohydrolase (PAP) activities. In the second model, rats were fed a diet enriched with sucrose, coconut oil and either sunflower oil (n-6 fatty acids) or fish oil (long-chain n-3 fatty acid ethyl esters). The treatment with n-3 fatty acids decreased serum triglycerides (41%) and, to a lesser extent, serum cholesterol (17%). Neither glycerol 3-phosphate acyltransferase (GPAT) or DGAT were affected by n-3 fatty acids. In contrast, PAP activity was reduced by 26%. HMG-CoA reductase was not significantly affected, whereas cholesterol 7 alpha-hydroxylase activity was reduced by 36%. The results indicate that part of the TG-lowering effect of long-chain n-3 fatty acids may be mediated by inhibition of the soluble phosphatidate phosphohydrolase. The effect on serum cholesterol may be partly due to inhibition of HMG-CoA reductase. PMID- 1895887 TI - Synthesis of 6-phosphatidyl-L-ascorbic acid by phospholipase D. AB - Phospholipase D (EC 3.1.4.4) of Streptomyces species was found to catalyze transphosphatidylation to L-ascorbic acid from phosphatidylcholine (PC) in a biphasic reaction system. The product was identified as 1,2-diacyl-sn-glycero-3 phospho-6'-L-ascorbic acid (PA-AsA) by mass spectrometry and nuclear magnetic resonance spectroscopy. The optimal pH of transphosphatidylation was 4.5 and the rate of PA-AsA formation increased as concentrations of L-ascorbic acid increased. The conversion of PC to PA-AsA was greater than 80%. PA-AsA was found to be more resistant to hydrolysis by phospholipase D than was PC. PMID- 1895888 TI - Effect of chitosan feeding on intestinal bile acid metabolism in rats. AB - The effect of chitosan feeding (for 21 days) on intestinal bile acids was studied in male rats. Serum cholesterol levels in rats fed a commercial diet low in cholesterol were decreased by chitosan supplementation. Chitosan inhibited the transformation of cholesterol to coprostanol without causing a qualitative change in fecal excretion of these neutral sterols. Increased fiber consumption did not increase fecal excretion of bile acids, but caused a marked change in fecal bile acid composition. Lithocholic acid increased significantly, deoxycholic acid increased to a lesser extent, whereas hyodeoxycholic acid and the 6 beta-isomer and 5-epimeric 3 alpha-hydroxy-6-keto-cholanoic acid(s) decreased. The pH in the cecum and colon became elevated by chitosan feeding which affected the conversion of primary bile acids to secondary bile acids in the large intestine. In the cecum, chitosan feeding increased the concentration of alpha-,beta-, and omega muricholic acids, and lithocholic acid. However, the levels of hyodeoxycholic acid and its 6 beta-isomer, of monohydroxy-monoketo-cholanoic acids, and of 3 alpha, 6 xi, 7 xi-trihydroxy-cholanoic acid decreased. The data suggest that chitosan feeding affects the metabolism of intestinal bile acids in rats. PMID- 1895890 TI - [Medical instrumentation at the "Health Care-90" exhibition]. PMID- 1895889 TI - Digestion and absorption of free and esterified fish oil fatty acids in rats. AB - This study was designed to test the hypotheses that digestibility and post absorption metabolism of fish oil are influenced by impaired lipolysis and by the stereospecific composition of its triacylglycerols. Male Wistar rats were fed nonpurified diets containing one of the following fat sources: 9% native fish oil (NFO), 9% autorandomized fish oil (RFO), 8.1% fish oil-derived free fatty acids (FO-FFA) plus 0.9% glycerol, or 9% soybean oil (SO) as a reference fat. In a 24 day balance study, apparent digestibility of total dietary fat averaged 93.1% in the SO, NFO and RFO groups, and 90.9% in the FO-FFA group. Randomization of fish oil had no effect on apparent digestibility of individual fatty acids. In rats fed FO-FFA, apparent absorption of saturated and monounsaturated fatty acids was lower when compared to the NFO and RFO groups. Feeding the FO-FFA diet tended to increase plasma triglyceride content. The hypocholesterolemic effect of polyunsaturated n-3 fatty acids was not influenced by the dietary source. Similar effects on fatty acid profiles of plasma and liver phospholipids were caused by the NFO, RFO and the FO-FFA diets. We conclude that once polyunsaturated n-3 fatty acids are absorbed, their effect on lipid metabolism is not determined by the dietary source. PMID- 1895892 TI - [Progress in the technology of medical instrumentation]. PMID- 1895891 TI - ["Health Care-90"--trends in the development of radio-electronic medical equipment]. PMID- 1895893 TI - [X-ray diagnostic computerized technique (based on materials of the International Exhibition "Health Care-90")]. PMID- 1895894 TI - [Medical equipment for utilizing intrahospital wastes]. PMID- 1895895 TI - [Equipment for therapeutic institutions and invalids (based on materials of the International Exhibition "Health Care-90")]. PMID- 1895896 TI - [Stomatologic equipment at the International Exhibition "Health Care-90"]. PMID- 1895897 TI - [Technical realization of an experimental model of a resonance mechanism of activating oxygen transport and consumption by hepatocytes]. AB - The authors review problems of oxygen regimen of the body under conditions of extracorporeal circulation. Provide the experimental data on the dynamics of oxygen consumption. Draw a based conclusion about a new approach to elaboration of the requirements for extracorporeal circulation systems. The paper may interest specialists engaged in the design and clinical application of the systems for extracorporeal circulation. PMID- 1895899 TI - [The main results of the International Exhibition "Health Care-90"]. PMID- 1895898 TI - [An expert system for choosing prostheses for the lower extremities (hip) and assessing the quality of the prosthesis. I]. AB - The authors describe the structure, characteristic features and experience gained with the employment of an expert system for the choice of hip prostheses (in cases of unilateral amputation) and assessment of the prosthetics quality. Word the requirements for hardware and software, present functional subsystems corresponding to certain interrelated stages of prosthetics. A variant has been devised of an appropriate training expert system with a profound representation of intelligence in an object area. PMID- 1895900 TI - [Results of clinical trials of the OTM-01A ophthalmic tonometer]. AB - An automatic ophthalmotonometer OTM-01A and Goldman's tonometer were employed to measure intraocular pressure in 28 patients suffering from glaucoma (54 eyes) and 14 patients without ophthalmotonus impairment (28 eyes). Comparison of the data showed lack of significant differences in the tonometric readings in both observation groups, which permits recommending the tonometer OTM-01A for practical uses. PMID- 1895902 TI - [The calculation of mixes for calibration of blood gas analyzers]. AB - The authors describe the design of a gas mixer operating on the basis of dynamic calibration, intended for use in an electronic blood gas analyzer. The influence of 3 different types of calibration throttles on the stability of components concentrations in a gas mixture is analyzed. PMID- 1895901 TI - [The choice of the mode of operation of the XeCl-laser for angioplasty]. AB - The authors relate the results of studies carried out on an outfit model for laser angioplasty designed on the basis of exiplex laser. Optimal conditions for laser introduction into a quartz guide have been found. It is shown that the efficacy of interaction between XeCl-laser and tissue rises as the intensity of radiation increases. The energy of radiation at the guide outlet being 9 mJ, the resources of fiber work remained at a high level (greater than 10(4) impulses) whereas high velocity of tissue evaporation allowed elimination of an area 3 mm3 in volume during 1 minute, with the rate of impulse repetition amounting to 10 Hz. PMID- 1895903 TI - [The functional characteristics of an additional dead space and a respirator for preparing hypoxic-hypercapnic mixtures intended for respiration training]. AB - A study was made of the characteristics of respiration recorded during the use of a respirator for preparing hypoxic hypercapnic mixtures as compared to the use of an additional "dead" space. In both cases, there was a significant increase of total ventilation, largely at the expense of respiration deepening. However, during respiration via a respiratory mask, the increase of the minute respiratory volume was accompanied by a rise of alveolar ventilation whereas during respiration via the ADS, alveolar ventilation dropped. Hyperventilation did not entail CO2 washing out from the blood and hypocapnia development during respiration via the mask and ADS. The differences revealed may appear helpful for respiration training at the hospital. In this case, an appropriate outfit should be sorted out for each patient on an individual basis. PMID- 1895905 TI - [Dynamic characteristics of element-by-element reproduction of visual matrix images: phenomenology and pharmaco-testing]. AB - An outfit "Mnemotest" was employed to examine some regularities of the operative memory of man. The dynamic characteristics are provided of reproduction-storage of the elements of visual matrix images: the curves of "fading" and the "reproduction tempo". It has been shown that oral administration in therapeutic doses of the psychostimulant sydnocarb optimizes the mnemonic processes. Under different conditions the drug either increases the "reproduction tempo" or minimizes the rate of the "fading" of the mnemonic trace. PMID- 1895906 TI - [A set of check-up means for an automatic microplate photometer for immunologic studies]. AB - The title set consists of six pairs of neutral filters with different optical density ranging from 0.03 to 1.5 B, a pair of filters made of colour yellow glass, and a holder having the same dimensions as the microplate and serving for the installation of the filters in the photometer checked. Every pair consists of two filters with identical optical parameters. The dimensions of the pair of filters allow covering all eight channels of the photometer simultaneously. The filters are certified with the error not more than +/- 0.003 B in the spectral range 360-700 nm. The yellow glass filter allows checking the dual wavelength mode of investigation. PMID- 1895907 TI - [An improved model of the EGDB-VO-4-M esophagogastroduodenoscope]. PMID- 1895904 TI - [Trends in the development of medical instruments and equipment (based on data of the International Exhibition "Health Care-90"]. PMID- 1895908 TI - [A branch conference on raising the safety of medical technological items]. PMID- 1895909 TI - [The development of medical equipment and items of ophthalmologic optics (based on materials of the International Exhibition "Health Care-90")]. PMID- 1895910 TI - ["Medicine Tropicale" is 50 years old]. PMID- 1895911 TI - [Visceral leishmaniasis in children. A study of hospitalized cases from 1974 to 1988 at the Children's Hospital in Tunis]. AB - The authors reported 122 cases of kala-azar admitted at Tunisian Children's hospital between 1974 and 1988. This affection was concerned male child and 78% of cases were aged less than 3 years old. The clinical feature was pallor, fever and splenomegaly. The diagnosis of kala-azar was established by serological test. The death rate was 8%. PMID- 1895912 TI - [Lymph node tuberculosis in Cameroon: clinical and anatomo-pathologic aspects; apropos of 333 cases]. AB - For a period of 11 years and 7 months (1st January 78-31 July 89), 1950 lymph nodes were received in the pathology laboratory of Cameroon. 333 of these, that is 17% revealed typical lesions of tuberculosis. Analysing the information associated to these tuberculoid adenitis revealed that: 46% of the patients were less than 10 years of age; 83.8% of the specimens were taken from the cervical region. 78% of patients had fever, cough was complained of by 56% and 40% had polyadenopathies. Finally, 81% of the tuberculoid lymph nodes analyzed had a diameter less than 5cm while only 33% showed acid fast bacilli on direct examination (Ziehl-Neelsen staining method) on the histologic slides. PMID- 1895913 TI - [The prevention of neonatal herpes encephalitis: characteristics in a tropical area]. AB - Neonatal herpes infection virus is rare but of poor prognosis. The only way to prevent it, is to practice a prophylactic caesarean section. In medically undeveloped countries, indication of caesarean section should be very prudent because of subsequent risks of uterine rupture. After a short recall about herpes illness, a precise and simple behaviour is proposed. PMID- 1895914 TI - [Hepatic amebiasis in French Polynesia. A study of 25 cases]. AB - The authors report a retrospective study of 25 cases of hepatic amebiasis which were observed from 1988 to 1990 in Tahiti. The symptoms were typical in 20 patients and incomplete in 5 other patients. The ultrasonic examinations showed one (n = 14) or several abscesses (n = 11). The majority were located at the right lobe of the liver (84%). Except in one case where the abscess had a high echo response (it was a pseudo-tumour), the others showed a low echo response or were liquid. The serology (hemagglutination) was always positive but once, at the first examination or afterwards. Recovery was obtained by all patients on an average of 6 days for clinical signs and of three months for ultrasonic features, by administering Metronidazole, combined twice with a drainage (transcutaneous = 1 case, surgical = 1 case). Neither rupture, nor relapse occurred. This series is related to other studies made in South Pacific, Africa and France. It underlines the topicality of amebiasis in French Polynesia, and the interest for the Health Services to carry out a program against this endemy. PMID- 1895915 TI - [Neurologic diseases in Niger]. AB - The authors report the results of a study realized at National Hospital of Niamey (Republic of Niger) from october 1981 to may 1986. Among 4820 patients living in Western Niger, 410 (8.5%) had neurological disorders. Out of 16 recognized syndromes 6 constitute 75.2%: comas, paraplegias, cranial nerves palsies, convulsions, hemiplegias and sciaticas. An etiological diagnosis is made in 269 patients. From 15 diseases 4 totalize 73.5%: there are medullar compressions, infections of the central nervous system (bacterial meningitis, cerebral malaria), cerebral vascular disturbances and metabolic encephalopathies. POTT's disease is the most common cause of medullar compression with paraplegia and arterial hypertension is a very important etiologic factor of cerebral vascular attack (42.2 and 44.4% respectively). Parkinsonian syndrome and multiple sclerosis seem rare. The diagnosis of cerebral tumor is very uncommon but this is in relation to the absence of autopsy and of recent investigation (scanner). No case of tuberculous meningitis is noted and this can't be explained by the authors in a major tuberculous endemic area. PMID- 1895916 TI - [Painful ophthalmoplegia of Tolosa-Hunt syndrome. 4 Nigerian cases]. AB - The Tolosa-Hunt syndrome is a painful ophthalmoplegia in relation with a granulomatous lesion of the cavernous sinus of obscure etiology. The authors report 4 cases diagnosed at National Hospital of Niamey (Republic of Niger). They were 3 men and one woman. The unilateral retro-orbital cephalalgia was constant. Three patients had left oculomotor and abducens nerves' palsies and one only left trochlear nerve's palsy. In three cases the therapeutic efficacy of systemic corticosteroids was dramatic with complete remission of clinical signs. In a fourth case, chlorambucil was used with complete recovery. PMID- 1895917 TI - [Non-groupable streptococci: identification, sensitivity to antibiotics (Charles Nicolle Hospital in Tunis)]. AB - 50 strains of viridans streptococci isolated from human material are identified by biochemical tests (bile esculin, Cl Na 6,5%, acid production from lactose, mannitol, sorbitol, inulin, arginine, esculin and starch hydrolysis; production of levan and dextran in sucrose media) Streptococcus salivarius and Streptococcus mitis are predominant species. Susceptibility to antibiotics was studied: 70% of viridans streptococci were susceptible to all antibiotics tested, high level resistance to aminoglycoside was not present. The only resistance observed were to tetracycline, macrolides and related drugs. PMID- 1895918 TI - [Plasmodium falciparum travels by train from Ethiopia to Djibouti]. AB - To investigate the role of the Djibouti-Ethiopian railway as a potential vehicle for inter-regional spread of malaria vectors and malaria parasites, we performed a double-sided study, both entomological and parasitological, during November 1989, at the frontier post of Guelile where the trains from Ethiopia enter the Republic of Djibouti. No malaria-transmitting mosquitoes were collected either from the daily passenger train or from the weekly vegetables train. One hundred and five passengers entering Djibouti by train from Ethiopia had a thick film examined for malaria parasites. Five smears were positive for Plasmodium falciparum, among them two showed gametocytes. We conclude that the railway may be an effective route for the propagation of the human malaria parasite between Ethiopia and Djibouti. Indeed, passengers infected abroad could import plasmodia into Djibouti and thus become the index cases for local malaria outbreaks, in case the climatic and entomological prerequisites essential for sustaining malaria transmission are present. PMID- 1895919 TI - [New approaches to phycomycoses (apropos of 2 cases of rhino entomophthoromycosis)]. AB - It is an uncommon affection (only 100 cases reported), observed primarily in African peri-equatorial zone. The rhinoentomophtoromycoses are caused by a phycomycetous fungus, class of zygomycetes: Conidiobolus coronatus. They are subcutaneomucus mycoses with centro-facial localizations. During the past ten years, three points have been put into light. 1. A true therapeutic revolution thanks to imidazoles. 2. A better knowledge of this disease in which caricatural forms are far form being the most numerous. 3. A socio-cultural African approach better understood, as such a disease is still considered as the result of a transgression or a fault. PMID- 1895920 TI - [Otorhinolaryngologic aspects of Kaposi's sarcoma in Africa]. AB - Such aspects are numerous from a disease with multiple factors among them immunodeficiency playing a key-role. O.R.L. aspect are more frequently observed than some ten years ago: this is mainly due to Kaposi's sarcoma in its epidemic form. Nevertheless one has to keep in mind that Kaposi's sarcoma in this endemic african form coexists with its second form without any well-marked border. Finally, many uncertainties are still existing among others its very peculiar cancerous nature. PMID- 1895921 TI - [Dissimilar glucose-6-phosphate dehydrogenase (G-6-PD) deficiency in the Afars and the Somalis of Djibouti]. AB - In order to determine the prevalence of deficient activity of the enzyme glucose 6-phosphate dehydrogenase (G-6-PD) among the inhabitants of the east African Republic of Djibouti, we analyzed by the methaemoglobin reduction test the blood of 170 Djiboutian males, 81 Afars and 89 Somalis. Eight subjects were found to be G-6-PD deficient, 1 Afar and 7 Somalis (1.2% versus 8%; P = 0.02). We conclude that in Djibouti, health care providers should consider the presence of potential G-6-PD deficiency in their patients, especially in males of the Somali ethnic group. Indeed, many medications are contraindicated in the G-6-PD deficient subjects, and primaquine and pyrimethamine-sulfadoxine (FANSIDAR) have to be considered dangerous anti-malarial drugs for Somali males as long as their level of G-6-PD activity has not been determined. Since in Djibouti many acute falciparum cases are presenting with severe icteric anaemia, we hypothesize that some of these haemolytic anaemias might not be caused by the parasitic infection alone, but that some malaria patients might become aggravated through the administration of haemolytic drugs in case they are G-6-PD deficient. Finally, we propose that our study should be expanded to include the systematic determination of the variants of the enzyme in all subjects found G-6-PD deficient, since the clinical manifestations of G-6-PD deficiency are directly related to the type of variant present. PMID- 1895922 TI - [A case of Burkitt's lymphoma with maxillofacial involvement in an human immunodeficiency virus (HIV) seropositive Burundi young adult]. AB - A 30 years old African, heterosexual and HIV positive, was found with Burkitt's lymphoma (B.L.) localized on the maxillofacial area. The authors explain the rarity of the localization on the maxillo-facial area in temperate countries where Burkitt's lymphoma usually is multivisceral localized. PMID- 1895923 TI - Identification of Streptococcus pyogenes proteins that bind to rabbit kidney in vitro and in vivo. AB - Proteins were extracted from the surface of a nephritogenic strain of Streptococcus pyogenes M12 and tested for binding to rabbit kidney using indirect immunofluorescence and enzyme-linked immunoassays. Streptococcal antigens bound in vitro in a fine linear pattern to basal laminae of glomeruli, Bowman's capsule, and tubules. Perfusion of rabbit kidney in vivo with streptococcal components resulted in focal and segmental fine granular staining of glomerular capillaries. Three streptococcal proteins (43, 31 and 9 kDa) were recovered from renal tissue that was pretreated in vitro with S. pyogenes extract. Streptococcal components bound in vitro to heparan sulfate, heparin, laminin and collagen IV but only weakly or not at all to fibronectin, bovine serum albumin or dextran sulfate. Affinity chromatography of bacterial extracts on heparin-agarose produced a 9 kDa streptococcal protein (pI 9.5) which bound to kidney basement membranes in vitro and in isolated perfused kidneys. Several additional strains of group A streptococci were found to contain the 9 kDa cationic protein. This bacterial protein, when released into the blood by the bacterium during infection, may contribute to the pathogenesis of streptococcus-associated nephritides in man. PMID- 1895924 TI - Comparison of host responses after intranasal infection of guinea-pigs with Mycoplasma genitalium or with Mycoplasma pneumoniae. AB - Guinea-pigs were infected intranasally with Mycoplasma genitalium or Mycoplasma pneumoniae. The lung lesions produced by the two mycoplasmas were comparable in extent and histological pattern. Sera of both animal groups taken 2 weeks after infection reacted strongly in the complement fixation test with the M. pneumoniae glycolipid extract. In an ELISA using the respective adherence proteins (P1 protein of M. pneumoniae and MgPa of M. genitalium), strong specific activity, but also considerable cross-reactions were found. Epitope analysis by using overlapping octapeptides of a P1-region immunologically active in human M. pneumoniae infections and of the corresponding MgPa-region revealed six common epitopes but also one M. genitalium and two M. pneumoniae specific determinants. For analysis of a possible pathogenicity of M. genitalium in the human respiratory tract species-specific tests have to be developed. PMID- 1895925 TI - Interactions of Haemophilus influenzae with cultured human endothelial cells. AB - The interactions of capsulate (b+) and capsule-deficient (b-) Haemophilus influenzae type b with endothelial cells were studied in vitro using human umbilical vein endothelial cells (Huvecs). Association was determined by estimation of colony forming units (cfu) as well as the binding of 3H-thymidine labelled bacteria. Bacteria associated with Huvecs rapidly and in a dose dependent manner. The presence of capsule on bacteria resulted in a decrease in the rate of cell-association. Internationalisation of bacteria by Huvecs was quantitated after elimination of extracellular bacteria with gentamicin. It was found that larger numbers of b- bacteria were internalised compared to b+ bacteria. Incubation in the presence of metabolic inhibitors had little effect on the association of bacteria to Huvecs whereas internalisation was dependent on the integrity of host cellular functions. Electron microscopic studies confirmed phagocytic ingestion of both b+ and b- variants and suggested that the majority of the internalised bacteria remained viable within endothelial cell vacuoles. Haemophilus influenzae were translocated within vacuoles both from the apical to basal and the basal to apical direction. PMID- 1895926 TI - Mechanisms of herpesvirus immuno-evasion. PMID- 1895927 TI - Complement-mediated serum activities against genetically defined capsular transformants of Haemophilus influenzae. AB - Although there are six different capsular serotypes of Haemophilus influenzae (a f), only type b strains commonly cause systemic infections in man. The present study was performed to determine whether the propensity of the type b organism to cause invasive infections is due to a unique ability to evade complement-mediated host defenses. The ability of genetically defined capsular transformants (a-f) of an unencapsulated H. influenzae to resist the bactericidal and opsonic activities of serum was examined. The unencapsulated organism and the type f transformants were relatively susceptible to serum bactericidal activity in both adult and infant serum pools, the type a and e transformants were relatively resistant, and the types b, c and d transformants were intermediate. With respect to serum opsonic activity in both adult and infant serum pools, the unencapsulated organism and the type f transformant were relatively susceptible, the type a, b and e transformants were relatively resistant and the type c and d transformants were intermediate. Thus, although the type b capsule endows the organism with the ability to resist the bactericidal and opsonic effects of complement, this property is not unique to type b. PMID- 1895928 TI - Characterization of a non-hemolytic mutant of Actinobacillus pleuropneumoniae serotype 5: role of the 110 kilodalton hemolysin in virulence and immunoprotection. AB - To determine the role of hemolysin(s) in virulence and immunoprotection, non hemolytic mutants of Actinobacillus pleuropneumoniae serotype 5, strain J45, were isolated following chemical mutagenesis. One mutant was selected for extensive characterization. Differences in capsule content, or in lipopolysaccharide or membrane protein electrophoretic profiles of the parent and mutant were not detected. A predominant, calcium-inducible protein of 110 kDa was present in culture supernatant of the parent, but absent from the mutant. Two-dimensional (2 D) gel electrophoresis confirmed that the 110 kDa protein was absent in culture supernatant of the mutant, but few, if any, minor differences could be detected in whole-cell proteins between the parent and mutant. The mutant totally lacked extracellular hemolytic and cytotoxic activity. Lysates of whole cells of the mutant contained weak hemolytic activity, and the 110 kDa protein could be detected by immunoblotting. Neutralization titers were negative in pigs immunized with the mutant or purified, denatured hemolysin, although enzyme-immunoassay titers were detected. Four additional independently isolated non-hemolytic mutants were avirulent in pigs and mice at doses greater than 10 times the lethal dose of the parent. Neither pigs nor mice were protected against lethal infection following immunization with the non-hemolytic mutant. We conclude that the 110 kDa hemolysin plays an important role in bacterial virulence and the pathogenesis of pleuropneumonia, and that sufficiently high levels of neutralizing antibodies to the 110 kDa hemolysin may be required for protection of pigs against disease. PMID- 1895929 TI - A 'safe-site' for Salmonella typhimurium is within splenic cells during the early phase of infection in mice. AB - Salmonella typhimurium infection in mice is focused on the spleen and liver, and prolonged infection can lead to sepsis and death. After intravenous infection with a moderate dose of S. typhimurium, the few bacteria that survive in the spleen and liver grow in a 'safe-site' where they are protected from immune destruction. In this study, we demonstrated that the lack of killing of resident salmonella in the spleen and liver was not because the salmonella were transformed within the host and became resistant to killing, or because the infected mice lost the ability to kill salmonella. We showed that the salmonella were within an intracellular 'safe-site' that protected them from killing. Brief treatment of salmonella-infected mice with gentamicin reduced the numbers of salmonella in the blood but had no effect on the numbers in the liver and spleen, suggesting an intracellular location of the salmonella. After dissociation of spleen cells from recently infected mice, 60% of the salmonella remained cell associated. These cell-associated salmonella, unlike cell-free salmonella, were resistant to killing by gentamicin. The cell-associated salmonella were rendered susceptible to gentamicin after sonication, providing confirmation of their previous intracellular location. PMID- 1895930 TI - Characterization of outer membrane and secreted proteins of Leptospira interrogans serovar pomona. AB - Outer membrane and secreted proteins were isolated from Leptospira interrogans serovar pomona and characterized by sodium dodecyl sulfate polyacrylamide gel electrophoresis, immunoblot and radioimmunoprecipitation techniques. The L. interrogans outer membranes were extracted with Triton X-114 and contained several proteins. The major cellular protein with a molecular mass of 31 kDa was associated exclusively with the L. interrogans outer membrane. Using a whole cell immunoprecipitation method, five hydrophobic, Triton X-114 extractable proteins (22, 26, 31, 36 and 42 kDa) were exposed on the surface of L. interrogans. The 31 kDa protein was heat labile and was a potent antigen in animals experimentally infected with L. interrogans serovar pomona. Several proteins were secreted by L. interrogans including a 60 kDa protein tentatively identified as the L. interrogans hemolysin. PMID- 1895931 TI - Replantation of severed fingers: two unique cases. AB - Two cases of amputated digits are reported. One involved a period of ischemia at freezing temperatures, and the other at unusually high temperatures. Both fingers survived upon replantation. The implications of extreme temperature upon ischemic tissues are discussed. PMID- 1895932 TI - Root reconstruction for bladder reinnervation: an experimental study in rats. AB - Nerve transfer (or nerve crossover) is a well established technique for achieving reinnervation of a valuable sensory or motor territory by reconnection using a functional nerve of lesser value. Patients with lower spinal cord lesions causing neurogenic bladder dysfunction could theoretically benefit from such an approach for return of useful micturition. Based on the known anatomical details of the spinal nerve, a new reconstructive method was created to provide intradural ventral root transfer for pure motor-to-motor reinnervation and extradural postganglionic spinal nerve transfer for pure sensory-to-sensory reinnervation. Experimental studies in rats were performed, demonstrating the feasibility of this approach. A modified method is further suggested that would use nerve grafts for extradural approaches to pure motor and sensory transfers, without the need for extensive laminectomy and dura opening. This proposed approach is anticipated to minimize the associated morbidity and mortality with such spinal nerve reconstruction. PMID- 1895933 TI - Laser Doppler bone probe: an experimental study in dogs. AB - Immediate reintervention is necessary when vascular insufficiency is suspected in free bone transfers. We tested the reliability of the laser doppler bone probe in recording steady state and arterial and venous occlusion. During steady state the flux signal was not constant but fluctuated. During arterial occlusion an immediate and reproducible decrease in flux signal was seen. No evident changes were seen during venous occlusion. These results have clinical importance in monitoring free bone transfers. PMID- 1895934 TI - Effects of venous hypertension on rabbit free flap survival. AB - A two-stage project was developed to study the effect of increased venous pressure on blood flow and survival in microvascular free tissue transfers. A rabbit epigastric fasciocutaneous free flap model was used. The blood flow in the rabbit epigastric free flap is 1.07 +/- 0.06 ml/min. The average venous pressure is 8.6 +/- 1.7 cm water. A logarithmic relationship between blood flow and venous pressure was demonstrated, with a statistically significant decrease in blood flow to 20-35% of the control values when the venous pressure rose above 28-30 cm water. This study stands in support of the tolerance by free tissue transfers of pressures below this range. The results further show a positive correlation between increasing venous pressure and free flap failure. PMID- 1895935 TI - Microvascular transfer of anterior and posterior gracilis muscles in rats. AB - A microvascular free muscle flap in rats using the anterior and posterior gracilis muscles with femoral vessels as its pedicle is presented. The gracilis muscles form a single unit supplied by the muscular branch artery and vein, averaging 0.3 mm and 0.4 mm in diameter, respectively. These small sizes preclude their use in transplantation. However, the muscular branch vessels in continuity with the femoral vessels can be used for the vascular pedicle in this muscle transplant. This muscle flap was transplanted to the contralateral femoral vessels by end-to-end anastomosis in 15 rats. Thirteen animals survived and 11 flaps were viable at 3 days for a success rate of 85%. The gracilis flaps averaged 674 mg in weight, 1.87 cm X 1.36 cm in size, and 7.23 mm in pedicle length. This free muscle flap model is reliable, relatively easy to perform, and provides adequate muscle bulk for pharmacologic and biochemical studies in transplanted muscle. No lower extremity complications were noted following femoral vessel ligations. PMID- 1895936 TI - Refined technique for intestinal transplantation in the rat. AB - Unlike other solid organ transplants, intestinal transplantation (IT) remains a highly experimental procedure. Rejection, sepsis, and graft-versus-host disease have been the major barriers to successful IT in humans. These problems can be studied in the rat model, but this requires a reliable surgical technique that will produce high survival rates and excellent graft function. Herein, we review 400 consecutive IT in rats and describe important technical aspects of surgery. Technical modifications that have helped to reduce the morbidity after IT in rats include 1) minimizing mechanical and ischemic injuries to grafts during the donor procedure, 2) marking the portal vein and aortic conduit with sutures to ensure correct orientation of the graft, 3) using a macaroni noodle to stent the intestinal anastomosis, and 4) administering large volumes of crystalloid to maintain a normal blood pressure during the donor and recipient surgeries. The survival rate in 298 rats with accessory, heterotopic grafts was 90%. The survival rate in 102 rats with orthotopic (in continuity) graft (OIT) was 86%. Rats have survived more than 500 days after OIT, maintaining normal weights, intestinal function, and intestinal histology. PMID- 1895937 TI - Use of anticoagulants in replantation and elective microsurgery. PMID- 1895938 TI - Topically applied antithrombotic agents offer a new therapeutic approach to the prevention of microvascular thrombosis. AB - In the quest to develop optimal antithrombotic therapies for reconstructive microsurgery, with concomitant minimization of patient risk for generalized hemorrhage, surgeons have been turning to localized intraarterial delivery of various agents. An extension of this direction is to design agents that bind specifically to the site of thrombogenesis and effectively inhibit or prevent the buildup of thrombotic components. Progress in this direction must make use of the latest developments in the molecular understanding of coagulation, platelet adhesion/aggregation, and fibrinolytic processes. This article reviews pertinent developments in the biochemical understanding of thrombosis and discusses current avenues of investigation in the development of topically applied agents that help prevent microvascular thrombotic occlusion. PMID- 1895940 TI - Selective heparinization of venous anastomosis in latissimus dorsi free flaps to cover lower-extremity soft-tissue defects. AB - Two groups of consecutive patients treated with latissimus dorsi free myocutaneous flaps to cover lower-extremity soft-tissue defects were compared for postoperative vascular occlusion. In the first group of 13 patients (group I), there were five (38%) venous occlusions and no arterial occlusions. The second group of 15 patients (group II) was treated with selective heparinization of each venous anastomosis via a 0.35" catheter sutured into the serratus branch of the donor vein. In this group one patient suffered an arterial occlusion, but no patient suffered a venous occlusion. Statistical analysis using the Fisher exact probabilities test showed a significant decrease in vascular occlusion rate in group II, proving that selective heparinization had a beneficial effect on the venous patency rate. PMID- 1895939 TI - Effect of desmopressin on vein graft patency in a microvascular model. AB - Desmopressin acetate decreases blood loss after cardiac surgery by activating platelets. We studied whether this effect was detrimental to small-caliber vein grafts in rats. Thirty minutes before femoral artery grafting with 0.75-mm diameter reverse autogenous saphenous vein grafts, 20 rats received desmopressin acetate intravenously at 1.0 micrograms/kg over 10 minutes, and 20 control rats received normal saline intravenously over 10 minutes. In each group, 10 rats received a 6-mm-long graft and 10 an 18-mm-long graft. Graft patency was evaluated at 20 minutes, 24 hours, and 30 days. Intimal thickening was assessed by light and scanning electron microscopy. At 30 days, 9 short grafts and 8 long grafts in the desmopressin-treated group were patent, whereas only 8 short control grafts and only 6 long control grafts were patent. Intimal thickening and platelet deposition were the same in both groups. These data show no detrimental effects of desmopressin acetate on saphenous vein graft patency. PMID- 1895941 TI - International survey of current microvascular practices in free tissue transfer and replantation surgery. AB - The replies to a questionnaire about current microvascular practice circulated to microsurgeons worldwide are summarized and discussed. The material comprises results of 6,594 procedures performed during 1989. The survey topics dealt with include overall success rates in free flap transfer and replantation surgery, antithrombotic therapy, frequency of thrombosis, and frequency of reoperation. At centres not using antithrombotic therapy, the frequency of thrombosis in free flap procedures was higher than at centres using antithrombotic therapy, the result being a higher reoperation rate at the former. However, the final success rates for free flap transfers were about the same (95-96%). The success rate for replantation with antithrombotic therapy was 92%; few centres attempted replantation without such treatment, and at these centres, the success rate was 82%, and reoperation was not attempted. The same modes of antithrombotic therapy and postoperative monitoring are used worldwide. PMID- 1895942 TI - Recency effects in direct and indirect memory tasks. AB - In three experiments, subjects learned two lists under incidental conditions and were then given either a part-word or a word (extralist associate) cue. Each cue was related to one word in each list. Half the subjects were given production instructions (an indirect memory test), and half were given cued recall instructions (a direct memory test). When the interval between List 2 and the test was shortened, recency effects were found for part-word cues for both cued recall and production instructions. Little or no recency effects were found with word cues. These results are incompatible with a simple distinction between the types of memory trace or information that are tapped by direct as opposed to indirect memory tasks. Possible causes for the recency effect and for the difference between word and part-word cues are discussed. PMID- 1895943 TI - Positional uncertainty in long-term memory. AB - Long-term memory for position was examined from the perspective of an immediate memory framework, the perturbation model of Estes (Estes, 1972; Lee & Estes, 1977, 1981). First, a simple version of the perturbation model is shown to provide a reasonable fit of previously reported long-term data (Nairne, 1990b), even though the perturbation idea was developed to explain the phenomena of immediate retention. Second, new results are reported that extend the application to multiple dimensions. Long-term memories for list and within-list position appear to mimic the classic patterns of immediate retention, in that both show bow-shaped serial position curves and error generalization gradients that are roughly symmetrical around the true serial position. PMID- 1895944 TI - The interpretation of isolated novel nominal compounds. AB - The lexical decision task was used to investigate interpretative processing of isolated novel compounds (noun-noun nominals). On the basis of interpretability ratings, novel compounds were classified as being of either high or low interpretability. In a lexical decision task in which novel compounds functioned as nonwords, a significant interference effect was found for compounds of high interpretability. In a naming task, no differences were found between the two types of novel compounds, but lexicalized compounds resulted in shorter latencies than did novel compounds. Novel compounds were also shown to be interpreted under conditions unfavorable to morphological decomposition, suggesting that the interpretation process is beyond strategic control by the subject. Equal semantic priming effects were obtained for members of established semantic categories and nouns of highly interpretable compounds. Interpretative processes dealing with a limited set of basic semantic relations and analogy with lexicalized compounds are discussed. PMID- 1895945 TI - Instrumental judgment and performance under variations in action-outcome contingency and contiguity. AB - The intentional theory of instrumental performance proposes that performance of an action is determined in part by a belief about its causal effectiveness in producing a desired outcome. At variance with this notion, previous implicit learning experiments appear to have yielded dissociations between subjects' performance and beliefs. In two experiments, subjects were given an opportunity to perform an action--pressing a key on a computer keyboard--which was associated with an outcome on the computer screen according to a free-operant contingency. The subjects in one group were asked to judge the effectiveness of the action in causing the outcome, while those in a second group were asked to maximize their points score under a payoff schedule. In the first study, the effect of varying the contingency between the action and outcome was examined by keeping the probability of an outcome contiguous with an action constant and varying the probability of an outcome in the absence of an action. Performance and judgments showed a comparable sensitivity to variations of the instrumental contingency. In the second study, the delay between the action and the resultant outcome was varied. Increasing the action-outcome delay from 0 sec up to 4 sec produced a systematic decline in both causal judgments and performance relative to noncontingent, control conditions. These results are in accord with the intentional theory of performance, but they present difficulties for the notion of implicit learning. PMID- 1895946 TI - Contextual dependencies in motor skills. AB - The development of contextual dependencies during motor skill acquisition was examined. Environmental context was varied along intentional and incidental dimensions. Intentional stimuli were defined as essential for achieving skilled performance, whereas incidental stimuli were defined as those that have the potential to become associated with specific tasks due to their selective presence in the learning environment. Experiment 1 demonstrated the occurrence of contextual dependencies for the learning of four-key typing sequences. Contextual dependencies were diminished in Experiment 2 when the number of keys used in the sequences was reduced. In Experiment 3, a retention condition was incorporated, in which both the intentional and the incidental stimuli were not available; this confirmed that task difficulty mediated the development of contextual dependencies. These findings are discussed with respect to the incorporation of environmental contextual stimuli with memorial representations of movement information. PMID- 1895947 TI - Ineffectiveness of visual distinctiveness in enhancing immediate recall. AB - Glenberg (1984) and others have theorized that greater recency effects are obtained with auditory as opposed to visual presentation because of greater temporal distinctiveness of items in auditory sequences. We tested a number of ways of enhancing visual distinctiveness, including the use of color, spatial location, and minimized visual interference. None of the seven experiments provided any evidence of improved recall from enhanced visual distinctiveness. In particular, no increase in recency effects was obtained with increased distinctiveness. Additional analyses of pairwise dependency in recall across serial positions also failed to show any evidence of the near-independence of recall of the terminal item that characterizes recall of auditory sequences. Visual-perceptual distinctiveness does not get mapped in any simple way onto memorial distinctiveness in an immediate-serial-recall task. PMID- 1895948 TI - Infant memory for place information. AB - The present studies were designed to examine the role of place cues in memory retrieval during early infancy. Three-month-old infants were trained to move a mobile by kicking. Two weeks later, memory retrieval was disrupted if they were reminded in a location or place different from where they had been trained, but not if they were reminded in the same place (Experiment 1A). The same result was obtained even though highly salient cues in their immediate visual surround remained unchanged during reminding (Experiments 1B and 1C). No disruption was seen, however, when retrieval was cued in a different place after only 1 day (Experiment 2). These findings unequivocally demonstrate that infants as young as 3 months encode incidental information about the place where an event occurs and suggest that early memories are buffered against retrieval in potentially inappropriate contexts over the long term. PMID- 1895949 TI - The role of assembled phonology in reading comprehension. AB - The contribution of assembled phonology to phonological effects in reading comprehension was assessed. In Experiment 1, subjects judged the acceptability of sentences with regular, exception, and nonword homophone substitutions and orthographic controls. Significantly more errors occurred to sentences with regular-word homophones than to exception words, and error rates for nonword homophones were low and not significant. Experiment 2 showed that this was not due to differences in the sentence frames. In Experiment 3, the subjects judged as unacceptable those sentences containing an exception word that sounded correct when read according to spelling-to-sound rules. Significantly higher error rates occurred only for low-frequency exception words. Experiment 4 showed that task conditions affect semantic-categorization error rates for nonword homophones. These results indicate that both assembled and addressed phonology contribute to sentence and word comprehension, but the low error rate for nonwords suggests that an early lexical check may be applied. PMID- 1895950 TI - Memory for musical surface. AB - This study of memory for music presented listeners with the first half of a short piano piece, O. Messiaen's Mode de valeurs et d'intensites. The piece is written according to a unique compositional principle that rigidly couples values of pitch (chroma and octave), duration, and dynamics. Listeners heard test excerpts, which were judged in terms of whether or not they might have come from the piece (either from the part they had heard or from the remainder of the piece). Even in the first block of trials, listeners were able to recognize segments from the part of the piece they had heard, suggesting surprisingly accurate memory for surface characteristics. Listeners were also able to generalize to the rest of the piece, accurately judging segments from the part of the piece they had not heard. However, performance on four kinds of transformed segments showed that the abstraction of a piece's surface characteristics adopts rather loose criteria. Even highly trained professional musicians informed of the compositional constraints before the experiment were not sensitive to the specific couplings between musical parameters. Rather, listeners appeared to be sensitive to contour (the pattern of increasing and decreasing pitch) and global correlations between pitch height and duration, dynamics, and interval size. Performance did not change with repeated hearings of the music. PMID- 1895951 TI - Commentary on Wolford, Taylor, and Beck: The conjunction fallacy? PMID- 1895952 TI - Negative halothane-caffeine contracture test in mdx (dystrophin-deficient) mice. AB - The genetics of malignant hyperthermia (MH) are ill-understood; however, the association of Duchenne muscular dystrophy (DMD) with MH is well known. A deficiency of dystrophin is common to both the DMD and mdx mouse, an animal model for DMD. Using muscle contracture tests for MH, we have shown that in the mdx mouse there is no MH susceptibility, suggesting the lack of a direct role of the dystrophin in the development of MH syndrome. PMID- 1895953 TI - Partial characterization of the fructose-induced defect in very-low-density lipoprotein triglyceride metabolism. AB - Very-low-density lipoprotein triglyceride (VLDL-TG) catabolism was studied in rats receiving either fructose or glucose as a 10% drinking solution. Consumption of either of the hexoses for 16 hours significantly elevated postheparin plasma (PHP) lipoprotein lipase (LPL) activity compared with normal control animals. Prolonged feeding of the carbohydrates for 14 days abolished the higher LPL activities, which were similar to control levels. PHP hepatic lipase (HL) activity was significantly reduced in carbohydrate-fed rats compared with control animals despite the duration of feeding. The kinetic parameters Km and Vmax cannot be obtained with lipoproteins and so the first-order rate constant (k1) of triglyceride hydrolysis was used to assess the effectiveness of VLDL-TG as substrates for endothelial lipases. VLDL-TG from fructose and VLDL-TG from glucose donors was lipolyzed with PHP LPL and HL from normal rats. The k1 (fraction of VLDL-TG lipolyzed) of VLDL-TG was found to be lower when donors had been fed fructose compared with VLDL that had come from glucose-fed donors. Rates of VLDL-TG removal from fructose and glucose donors were determined simultaneously in perfused livers of normal control, fructose-fed, and glucose fed animals. Livers of fructose-fed animals cleared VLDL-TG at a slower rate than livers from glucose-fed or control rats. VLDL-TG from fructose-fed rats was cleared less effectively than VLDL-TG from glucose-fed rats in livers of both control and glucose-fed animals. We conclude that an impairment in the ability of fructose-fed rats to hydrolyze VLDL-TG, and of their livers to remove VLDL-TG, may in part explain fructose-induced hypertriglyceridemia. PMID- 1895954 TI - Evidence for peripheral impaired glucose handling in patients with connective tissue diseases. AB - Sixteen patients suffering from rheumatoid arthritis (RA) (n = 8), systemic lupus erythematosus (SLE) (n = 5), and systemic sclerosis (SSc) (n = 3), and 10 healthy subjects matched for age, sex, and body mass index, were submitted to an intravenous (IV) glucose tolerance test (GTT) (0.33 g/kg of body weight in 3 minutes) and to a euglycemic hyperinsulinemic glucose clamp to study insulin response and action. In the euglycemic clamp, along with the two insulin infusion rates (0.5 mU/kg.min from 0 to 120 minutes and 1 mU/kg.min from 121 to 240 minutes), a primed (20 microCi) continuous (0.2 microCi/min) infusion of 3H glucose allowed determination of glucose kinetics. Our data show that patients versus controls have (1) a significant increase in basal plasma insulin levels (87.2 +/- 14.8 v 41.3 +/- 6.0 pmol/L, P less than .05); (2) similar glucose induced acute insulin response; and (3) a lower glucose disappearance rate (Rd), glucose metabolic clearance rate (gMCR), and glucose infusion rate (GIR) when the lowest insulin infusion rate was delivered. These differences disappeared when the insulin infusion rate was doubled. Furthermore, basal plasma insulin levels and glucose disappearance rate significantly correlated with the main inflammatory indices of each disease studied. We conclude that in our patients impaired glucose handling is mainly due to peripheral insulin resistance. PMID- 1895955 TI - Understanding "insulin resistance": both glucose resistance and insulin resistance are required to model human diabetes. AB - A mathematical model of normal glucose/insulin homoeostasis has been based on the known, experimentally determined responses of the liver and periphery to different glucose/insulin concentrations. Different defects of glucose resistance and insulin resistance have been applied to the model to investigate the degree to which these abnormalities could successfully predict the range of fasting glucose and insulin values found in normal, obese, and diabetic subjects. Modeling glucose resistance or insulin resistance at the liver or the periphery alone did not increase the plasma glucose to levels observed in diabetes, even when associated with marked deficiency of beta-cell function. A defect of either glucose resistance or insulin resistance affecting both periphery and liver allowed a wider range of basal glucose and insulin concentration values, but resulted in unphysiologically low hepatic glucose output: with modeling insulin resistance, hyperglycemia suppressed glucose output, whereas with glucose resistance, raised insulin levels suppressed hepatic glucose output. A wide range of glucose and insulin values, with appropriate basal hepatic glucose output, could only be modeled by insulin resistance at both the liver and periphery with additional glucose resistance at the liver. The modeling results are in accord with investigative studies that suggest secondary hepatic and peripheral glucose resistance in response to hyperglycemia. Modeling provides a systematic means of examining the likely effect of different putative defects in a complex physiological system. PMID- 1895956 TI - Disturbance in the metabolism of 5'-methylthioadenosine and adenine in patients with neoplastic diseases, and in those with a deficiency in adenine phosphoribosyltransferase. AB - 5'-Methylthioadenosine (MTA) produced during the synthesis of polyamines is degraded to adenine by MTA phosphorylase. This pathway is considered to be the main source of endogenous adenine. We determined the concentrations of MTA and adenine in control subjects and in those with a pathological disorder. In patients with active leukemias, as well as with other types of malignancies, the concentrations of MTA and adenine in the urine were elevated. These changes seemed to be the result of an accelerated production of MTA due to an accelerated biosynthesis of polyamine. In patients with adenine phosphoribosyltransferase (APRT) deficiency, the concentrations of adenine in the urine were elevated, presumably due to a disturbance in the catabolism of adenine. Although adenine is a potent inhibitor of MTA phosphorylase, APRT-deficient patients did not excrete MTA into urine in concentrations significantly larger than noted for control subjects. However, the amount of MTA excreted positively correlated with that of adenine in these patients, hence that accumulated adenine probably had a slight, but positive, inhibitory effect on the degradation of MTA. PMID- 1895957 TI - Lipoprotein-apolipoprotein changes in renal transplant recipients: a 2-year follow-up. AB - Renal transplantation modifies the dyslipidemia characteristic of chronic renal failure (CRF). The change in lipoprotein and lipid values of 51 transplant recipients, on cyclosporine and corticosteroid treatment, was studied during 2 years after transplantation to examine the short- and medium-term variations of lipid metabolism. Compared with control values of (all in mg/dL) triglycerides (Tg) 111 +/- 44, very-low-density lipoprotein (VLDL) Tg 69 +/- 18, total cholesterol (Chol) 201 +/- 32, VLDL-Chol 32 +/- 9, low-density lipoprotein (LDL) Chol 118 +/- 28, and high-density lipoprotein (HDL) Chol 50 +/- 10, uremic patients pretransplantation exhibited values of Tg 200 +/- 82 (P less than .001), VLDL-Tg 133 +/- 70 (P less than .001), Chol 193 +/- 51 (NS), VLDL-Chol 52 +/- 16 (P less than .001), LDL-Chol 100 +/- 37 (P less than .007), HDL-Chol 40 +/- 16 (P less than .001), which changed to Tg 118 +/- 18 (P less than .001), VLDL-Tg 64 +/ 45 (P less than .001), Chol 223 +/- 48 (P less than .006), VLDL-Chol 26 +/- 33 (P less than .001), LDL-Chol 134 +/- 43 (P less than .001), at HDL-Chol 63 +/- 21 (P less than .001) at 3 months and Tg 135 +/- 76, VLDL-Tg 81 +/- 62, Chol 218 +/- 55, VLDL-Chol 22 +/- 20, LDL-Chol 139 +/- 46, and HDL-Chol 58 +/- 18 at 24 months without evidence of a significative variations in the 3- to 24-month posttransplant period.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1895958 TI - Forearm insulin- and non-insulin-mediated glucose uptake and muscle metabolism in man: role of free fatty acids and blood glucose levels. AB - Muscle can utilize glucose by two different mechanisms, one non-insulin-mediated and the other insulin-mediated. The aim of this study was to investigate and to quantify the influence of high and low free fatty acids (FFA) levels on muscle non-insulin-mediated glucose uptake (MNIMGU) and muscle insulin-mediated glucose uptake (MIMGU) and on muscle metabolism during euglycemia and hyperglycemia. Six healthy volunteers were submitted, in a random order, to a 2-hour euglycemic clamp (EC) followed by a 2-hour hyperglycemic (11 mmol/L) clamp (HC) under five different conditions: (1) somatostatin infusion (SRIF, 500 micrograms/h); (2) SRIF infusion preceded by a nicotinic acid analogue (acipimox, 250 mg orally, (3) SRIF plus insulin infusion; (4) SRIF plus insulin plus intralipid infusion; and (5) SRIF plus insulin infusion plus acipimox. In the postabsorptive state MNIMGU represented 71% of the total muscle glucose uptake (MGU) and during the EC a sharp reduction of FFA levels increased the MNIMGU by 10% (P less than .05), and an acute increase in FFA levels decreased the MNIMGU by 26% (P less than .05). MIMGU was significantly increased by 103% after acipimox administration (P less than .05) and was decreased by 65% during intralipid infusion (P less than .05). During HC, MNIMGU was not significantly influenced by low or high FFA levels, and MIMGU was not affected by a sharp lowering of FFA levels, but was significantly decreased (85%) during intralipid infusion. There was no significant difference in the lactate, pyruvate, and alanine balance across the forearm during EC and HC.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1895959 TI - Inhibition of gluconeogenesis by tolbutamide in isolated rat hepatocytes: modulation of glucose-6-phosphate substrate cycle. AB - In hepatocytes isolated from 24-hour fasted rats, the oral hypoglycemic agent tolbutamide (1 mmol/L) inhibited glucose formation from different concentrations (1 to 20 mmol/L) of galactose, dihydroxyacetone, glycerol, and a mixture of L lactate:pyruvate (molar ratio, 10:1). Parallel to the reduction of gluconeogenesis, tolbutamide stimulated L-lactate formation when cells were incubated with either galactose, dihydroxyacetone, or glycerol. All these tolbutamide effects occurred without significant modification of hepatocyte fructose-2,6-bisphosphate (F-2,6-P2) levels. Only when glucose was included in the incubation medium was the inhibition of gluconeogenesis caused by the sulfonylurea accompanied by a significant increment of the cellular F-2,6-P2 concentration. Under these conditions, tolbutamide potentiated the effect of glucose in promoting the increase of this regulatory metabolite, as well as the stimulation of glycolysis; in addition, tolbutamide increased the cellular pool of hexose-6-phosphates and the rate of tritium release from (2-3H)glucose. These results support the hypothesis that tolbutamide regulates hepatic glucose metabolism, at least, by modulating the glucose-6-phosphate substrate cycle. PMID- 1895960 TI - The effects of human proinsulin on glucose turnover and intermediary metabolism. AB - We compared the effects of human proinsulin and human insulin on glucose disposal, suppression of hepatic glucose production (HGP), and intermediary carbohydrate and lipid metabolism. Six young, lean, subjects underwent eight separate euglycemic clamps with low-dose intravenous (IV) infusions of insulin and proinsulin (four each). The insulin infusions gave steady-state levels of 0.08 +/- 0.004 (I1), 0.12 +/- 0.003 (I2), 0.18 +/- 0.07 (I3), and 0.25 +/- 0.06 nmol/L (I4). The proinsulin infusions were chosen to give steady-state levels approximately 20-fold higher on a molar basis than insulin, based on previous findings that proinsulin has only 5% to 10% the biological potency of insulin. Steady-state proinsulin levels were 1.2 +/- 0.04 (P1), 2.8 +/- 0.07 (P2), 4.5 +/- 0.3 (P3), and 6.9 +/- 0.3 nmol/L (P4). HGP was suppressed equally by proinsulin and insulin at the four dose levels. Percentage elevation of glucose disposal was significantly increased during each of the insulin infusions compared with proinsulin: I1 107% +/- 4%, P1 87% +/- 4% (P = .03); I2 143% +/- 7%, P2 125% +/- 12% (P = .01); I3 238% +/- 38%, P3 173% +/- 22% (P = .03); I4 283% +/- 17%, P4 178% +/- 11% (P = .002). Dose-response curve analysis demonstrated that proinsulin stimulated glucose disposal approximately 3.3% compared with insulin. The effectiveness of proinsulin in suppressing HGP was approximately 5% compared with insulin. Plasma nonesterified fatty acids, blood glycerol, and 3 hydroxybutyrate were suppressed by similar amounts during each of the four insulin and proinsulin doses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1895961 TI - Effects of dietary glucose or fructose on the secretion rate and particle size of triglyceride-rich lipoproteins in Zucker fatty rats. AB - Effects of dietary carbohydrate on the secretion rate and particle size of triglyceride-rich lipoproteins were examined in Zucker fatty rats fed fructose and glucose and were compared with those of Zucker lean rats. Carbohydrates were supplied as 10% drinking solutions for 14 days. As compared with lean rats, Zucker fatty rats had hyperinsulinemia and hypertriglyceridemia associated with an increased rate of triglyceride secretion into the circulation. Feeding fructose and glucose to fatty rats produced an increase in plasma glucose levels, whereas plasma insulin concentrations did not show significant changes. Neither fructose nor glucose supplementation produced significant changes in the rate of triglyceride secretion. Despite this, plasma triglyceride concentrations in fructose-fed fatty rats were twice as high as those in glucose-fed rats or those receiving no supplementary carbohydrate. Particle diameters of lipoproteins of density between 0.96 and 1.006 were larger in fructose-fed fatty rats than in those receiving no sugar. The results suggest that feeding fructose, but not glucose, into fatty rats is associated with an impairment of triglyceride removal and a resultant increase in plasma triglyceride concentration, the latter of which is accompanied by an increase in triglyceride contents in each particle. PMID- 1895962 TI - Vertebral bone density in insulin-dependent diabetic children. AB - To determine the effect of insulin-dependent diabetes mellitus (IDDM) on bone mass, we compared the trabecular and cortical bone density in lumbar vertebrae, measured by quantitative computed tomography (CT), in 48 white diabetic patients (23 females, 25 males; 5.2 to 19.6 years of age) with those of a control group of 48 healthy subjects, matched for race, sex, and age. Patients with neuropathy, retinopathy, nephropathy, and those with recent ketoacidosis were excluded from the study. The patient and control groups did not differ in sexual or skeletal maturation, weight, height, surface area, body mass index, abdominal fat, or paraspinal musculature. In diabetic children, cortical bone density was slightly but significantly lower than in controls (3.5% lower, P less than .02); there was no difference between patients and controls regarding trabecular bone density. The decrease in cortical bone density in the diabetic group did not correlate with age, sex, duration of diabetes, or glycosylated hemoglobin levels. These results suggest that in children with uncomplicated IDDM, decreased vertebral bone density is a minor abnormality that only affects cortical bone. PMID- 1895963 TI - Insulin resistance and hyperinsulinemia in patients with chronic congestive heart failure. AB - Congestive heart failure is a condition associated with increased plasma norepinephrine levels. Moreover, norepinephrine has been recently demonstrated to affect glucose homeostasis by decreasing insulin sensitivity. In the present study, eight patients suffering from chronic congestive heart failure and 10 healthy age- and body mass index-matched subjected were submitted to both an oral glucose tolerance test (OGTT; 75 g) and a euglycemic hyperinsulinemic glucose clamp. During the 360 minutes of the glucose clamp, insulin was infused at three different rates (25, 50, and 100 mU/kg/h), while D-3H glucose infusion allowed determination of glucose turnover. In basal conditions, patients versus controls had similar plasma glucose (5.2 +/- 0.1 v 4.9 +/- 0.2 mmol/L,P = NS), but higher plasma insulin (125.7 +/- 9.2 v 35.7 +/- 3.3 pmol/L,P less than .01), norepinephrine (5.39 +/- 0.13 v 1.47 +/- 0.22 nmol/L,P less than .001), and free fatty acid (FFA) (927 +/- 79 v 792 +/- 88 mumol/L,P less than .05) levels. In patients, basal plasma norepinephrine correlated with FFA levels (r = .65, P less than .025). After loading glucose, plasma glucose and insulin levels were still significantly higher in patients than controls. Euglycemic hyperinsulinemic glucose clamp produced a lower insulin-mediated inhibition of endogenous (hepatic) glucose production (HGP) and a greater increase in both glucose disappearance rate (Rd) and glucose metabolic clearance rate (gMCR) in patients than in controls during the first two insulin infusion rates (25 and 50 mU/kg/h). By contrast, these differences disappeared during the highest insulin infusion rate (100 mU/kg/h). Insulin-mediated decrease in plasma FFA levels was also lower in patients than controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1895964 TI - Metabolism of tritiated D-glucose in rat erythrocytes. AB - The metabolism of D-[U-14C]glucose, D-[1-14C]glucose, D-[6-14C]glucose, D-[1 3H]glucose, D-[2-3H]glucose, D-[3-3H]glucose, D-[3,4-3H]glucose, D-[5-3H]glucose, and D-[6-3H]glucose was examined in rat erythrocytes. There was a fair agreement between the rate of 3HOH production from either D-[3-3H]glucose and D-[5 3H]glucose, the decrease in the 2,3-diphosphoglycerate pool, its fractional turnover rate, the production of 14C-labeled lactate from D-[U-14C]glucose, and the total lactate output. The generation of both 3HOH and tritiated acidic metabolites from D-[3,4-3H]glucose indicated incomplete detritiation of the C4 during interconversion of fructose-1,6-bisphosphate and triose phosphates. Erythrocytes unexpectedly generated 3HOH from D-[6-3H]glucose, a phenomenon possibly attributable to the detritiation of [3-3H]pyruvate in the reaction catalyzed by glutamate pyruvate transaminase. The production of 3HOH from D-[2 3H]glucose was lower than that from D-[5-3H]glucose, suggesting enzyme-to-enzyme tunneling of glycolytic intermediates in the hexokinase/phosphoglucoisomerase/phosphofructokinase sequence. The production of 3HOH from D-[1-3H]glucose largely exceeded that of 14CO2 from D-[1-14C]glucose, a situation tentatively ascribed to the generation of 3HOH in the phosphomannoisomerase reaction. It is further speculated that the adjustment in specific radioactivity of D-[1-3H]glucose-6-phosphate cannot simultaneously match the vastly different degrees of isotopic discrimination in velocity at the levels of the reactions catalyzed by either glucose-6-phosphate dehydrogenase or phosphoglucoisomerase. The interpretation of the present findings thus raises a number of questions, which are proposed as a scope for further investigations. PMID- 1895965 TI - Comparison of reliability of plasma fructosamine and glycosylated hemoglobin assays for assessing glycemic control in diabetic patients on hemodialysis. AB - To search for a reliable marker of medium-term integrated blood glucose level in diabetics on maintenance hemodialysis (HD), plasma fructosamine and glycosylated hemoglobin (Hb) levels were determined every week and blood glucose levels were determined four times every day over 3 weeks. The mean values of fructosamine (mol/L per 40 g of albumin) and of glycosylated Hb of other the study period correlated (r = .746, P less than .001) for combined materials of diabetic and nondiabetic subjects. However, plasma fructosamine values at the end of the study period did not correlate with the overall mean blood glucose values during the preceding 8 to 21 days (r = .372, NS). In contrast, glycosylated Hb values correlated closely with the same mean blood glucose values (r = .703, P less than .001). Fructosamine values significantly decreased during a HD, irrespective of the increases in albumin and total protein. In conclusion, glycosylated Hb was a reliable marker of long-term integrated blood glucose even in diabetics on HD. However, fructosamine was not a reliable marker of medium-term integrated blood glucose in these patients. PMID- 1895967 TI - Computers and clinical decision-making. PMID- 1895966 TI - Regional differences in triglyceride breakdown in human adipose tissue: effects of catecholamines, insulin, and prostaglandin E2. AB - Regional variation of adipose tissue triglyceride breakdown (lipolysis) has been suggested to play a role for the health consequences of some forms of obesity. Thus, in the present study we investigated the regulation of lipolysis in isolated adipocytes obtained from different fat depots in females. Intra abdominal adipose tissue (omental) and subcutaneous abdominal adipose tissue were obtained from the same individuals undergoing abdominal surgery (n = 9); in addition, adipocytes from the subcutaneous gluteal region (n = 12) and from mammary adipose tissue (n = 5) were investigated. The lipolytic/antilipolytic properties of epinephrine (EPI), insulin, clonidine, and prostaglandin E2 (PGE2) were investigated. The most prominent observation was that EPI had none or only minor lipolytic effect in adipocytes from the subcutaneous regions, but significantly enhanced lipolysis by approximately 500% in omental adipocytes (P less than .001). In the presence of the alpha 2-adrenergic antagonist, yohimbine, EPI had similar stimulatory effects (fourfold to fivefold) in all fat depots. The antilipolytic compounds, insulin and clonidine, had greatly reduced antilipolytic properties in omental adipocytes as compared with subcutaneous adipocytes (P less than .01 and P less than .05, respectively). On the other hand, PGE2 had similar antilipolytic properties in adipocytes from the various depots. In conclusion, we found great regional variation in the regulation of lipolysis. Particularly, EPI was much more lipolytic in omental adipocytes than in subcutaneous adipocytes, mainly due to an enhanced functional alpha 2-receptor activity in subcutaneous adipocytes. These in vitro data suggest that free fatty acids (FFA) are more readily mobilized from omental adipose tissue than from subcutaneous adipose tissue. PMID- 1895968 TI - A chromosomal study of workers with long-term exposure to radio-frequency radiation. AB - OBJECTIVE: To examine whether an increased level of chromosome damage occurs in the stimulated lymphocytes of radio-linemen after long-term but intermittent exposure to radio-frequency radiation (RFR) during the course of their work. DESIGN AND PARTICIPANTS: Chromosome studies were performed on blood samples from 38 radio-linemen matched by age with 38 controls, all of whom were employed by Telecom Australia. The radio-linemen had all worked with RFR in the range 400 kHz 20 GHz with exposures at or below the Australian occupational limits, and the controls were members of the clerical staff who had no exposure to RFR. Two hundred metaphases from each subject were studied and chromosome damage was scored by an observer who was blind to the status of the subjects. RESULTS: The ratio of the rate of aberrant cells in the radio-linemen group to that in the control group was 1.0 (95% confidence interval, 0.8-1.3). There were no statistically significant differences in the types of aberrations that were scored. CONCLUSION: Exposure to RFR at or below the described limits did not appear to cause any increase in chromosomal damage in circulating lymphocytes. PMID- 1895969 TI - Early parental responses to sudden infant death, stillbirth or neonatal death. AB - OBJECTIVE: To examine the mental health of parents after stillbirth (SB), neonatal death (NND) or sudden infant death syndrome (SIDS). DESIGN: The sampling frame from southeast Queensland was observed over 2.5 years. Control families were matched for birth date, sex of child, hospital and health insurance status. SETTING: Home interviews, by specially trained social workers, took place two months after the death of the infant. PARTICIPANTS: Results were based on 918 responses from 260 bereaved families (99 SB, 109 NND, 52 SIDS) and 252 control families, with a 63.6% overall participation rate. MAIN OUTCOME MEASURES: Questionnaires included standardised measures of anxiety, depression, biographic and demographic data. It was hypothesised that subject families would show more symptoms of anxiety and depression than control families, with mothers and parents affected by SIDS having the highest levels. RESULTS: Affected parents report significantly more psychological symptoms than controls, mothers more than fathers (P less than 0.001). Parents affected by SIDS showed more symptoms than other affected parents. High levels of anxiety were 14 times more likely in mothers affected by SIDS than controls (95% confidence interval, 5.4-36.6), with depression 12 times more likely (95% confidence interval, 3.8-43.5). Anxiety for groups affected by SB and NND were respectively 3.9 (2.1-10.5) and 6.5 (2.6-16.3) times more likely than for controls, and depression 6.9 (2.1-22.5) and 8.5 (2.7 26.7) times more likely. Differences were less marked for fathers, except for fathers affected by SIDS. CONCLUSIONS: Parents affected by stillbirth, neonatal death or sudden infant death syndrome manifest high levels of anxiety and depression two months after the death. Mothers have more symptoms than fathers, and parents affected by SIDS have the most symptoms of anxiety and depression. PMID- 1895970 TI - Human immunodeficiency virus antibodies in sera of Australian blood donors: 1985 1990. AB - OBJECTIVE: To describe the results of human immunodeficiency virus type 1 (HIV-1) antibody testing of blood donations in Australia. DESIGN: Blood transfusion services tabulated the number of HIV-1 antibody tests carried out on blood donations and the number of donations found to be positive, from 1985 to 1990. SETTING: All blood transfusion services in Australia. PARTICIPANTS: All donors of blood in Australia from 1 May 1985 to 31 December 1990. OUTCOME MEASURES: The proportion of blood donations found to have HIV-1 antibody, according to State or Territory, year of donation and, when available, age, sex and donation status (repeat or first-time) of the donor. RESULTS: To the end of December 1990, 5,367,970 donations had been tested for HIV-1 antibody, and 46 were found to have the antibody, giving an overall prevalence rate of 0.86 per 100,000 donations. The highest rate was recorded in New South Wales, followed by Western Australia, and four of eight Australian States and Territories reported no donors with HIV-1 antibody. There has been no clear trend with time, but the rate is about 20% higher for 1989-1990 than for 1985-1986. Of donors found to have HIV-1 antibody, 67% were male and 33% female, and 41% reported no known or potential exposure to HIV-1 other than heterosexual contact. Among blood donors in two major Australian cities, the overall prevalence of HIV antibody was higher in those who were male, younger, and first-time donors. There has been a recent increase in the number of blood donors with HIV-1 antibody who were women reporting heterosexual contact as their only potential exposure. CONCLUSION: The rate of HIV-1 antibody in Australian blood donations remains very low and shows no clear temporal trend, but specific donor characteristics define higher rates of antibody prevalence. PMID- 1895971 TI - Household electric shocks: who should be monitored? AB - OBJECTIVE: To decide who should be monitored after exposure to household 240 volt 50 Hz alternating current electric shocks. DESIGN AND SETTING: Records of patients admitted to the Intensive Care Unit of Royal Perth Hospital for the period 1978-1987 were retrospectively reviewed. A literature review was also performed to compare previous findings with our own (Medline search; keywords- electrical injury, arrhythmia). RESULTS: There were 20 patients in the series, and all patients survived the electric shock. Of the 18 who presented with no cardiovascular symptoms or electrocardiographic abnormalities, none developed arrhythmias while being monitored in the Intensive Care Unit. CONCLUSION: Routine cardiac monitoring is not required after electric shock with household alternating current if the patient is asymptomatic and has a normal electrocardiogram on presentation. PMID- 1895972 TI - Polysomnography at a sleep disorders unit in Melbourne. AB - OBJECTIVE: To outline the procedure of polysomnography as carried out in a sleep disorders unit in Melbourne and to describe the patients undergoing polysomnography in terms of their age and sex and the sleep disorder diagnosed. DESIGN: A retrospective survey of consecutive patients who required diagnostic polysomnography. SETTING: The Sleep Disorders Unit at Epworth Hospital, a large private hospital in Melbourne. PATIENTS: Two hundred consecutive patients who underwent polysomnography over a seven-month period. Their ages ranged from 19 to 77 years. INTERVENTIONS: All patients had diagnostic polysomnography for one night in the sleep laboratory. This involved 12 to 14 physiological variables being monitored continuously overnight by means of a new digital recording and sleep analysis system. MAIN OUTCOME MEASURES: Patients were categorised according to their main sleep disorder or primary diagnosis. Additional sleep disorders in some patients were categorised as secondary diagnoses. RESULTS: The commonest age group among both male and female patients was 40-49 years. Overall, men outnumbered women three to one. Almost two-thirds of all patients had as their primary diagnosis some degree of obstructive sleep apnoea syndrome or simple snoring. The next most common diagnosis was periodic limb movement disorder. The remaining diagnoses included a variety of sleep disorders, from narcolepsy to sleep terrors. CONCLUSIONS: Despite its complexity and time-consuming nature, polysomnography is an essential procedure for the diagnosis and treatment of a wide range of sleep disorders. More sleep laboratories and a greater emphasis on the multidisciplinary teaching of sleep disorders medicine will be required in Australia. PMID- 1895973 TI - Child abuse. PMID- 1895974 TI - Pre-travel health care. PMID- 1895975 TI - GPs as learners. PMID- 1895976 TI - The GP as a teacher. PMID- 1895977 TI - Reproductive health: knowledge, attitudes and needs of adolescents. AB - OBJECTIVE: To determine the knowledge and attitudes of adolescents with respect to reproductive health, with particular emphasis on their knowledge of the symptoms and transmission of sexually transmitted diseases (STDs), preventive strategies and sources of information. DESIGN: Questionnaire survey of a stratified random sample of Year 10 students followed by group interviews with volunteers from the sample. SETTING: The study was carried out in 33 Victorian secondary schools. PARTICIPANTS: The questionnaire was administered to a stratified random sample of 1351 Year 10 students. Group interviews were conducted with 533 volunteers from the sample. MEASUREMENTS AND MAIN RESULTS: Considerable gaps were identified in knowledge of STDs and their short-term and long-term effects on reproductive health. An STD Knowledge Score was constructed based on responses to 46 items. The mean score for the full sample was 22.7 (49.3% correct) with a standard deviation of 6.4. As a group, country students scored better than city students (mean, 23.8 v. 22.2, t = 3.97, P less than 0.001) and females better than males (mean, 23.5 v. 21.9, t = 4.21, P less than 0.001). Medical practitioners were rarely identified as a source of preventive advice. CONCLUSION: The deficiencies identified in knowledge about reproductive health suggest that young people need better access to health information. Schools and the medical profession need to work together both to provide information and to help young people develop the confidence to use available information sources. PMID- 1895978 TI - Failure to demonstrate contrast nephrotoxicity. AB - OBJECTIVE: We tested the hypothesis that there is no difference in the change in serum creatinine level following computed tomography (CT) between those given high osmolality contrast, low osmolality contrast and those not receiving contrast material. DESIGN: Patients were assigned according to current radiological practice to receive one or other type of radiocontrast material or to have a scan without intravenous contrast (plain scan). SETTING: The CT unit of Royal Newcastle Hospital, a tertiary referral institution. PATIENTS: Of 3188 inpatients having a CT scan between June 1988 and December 1989, 1041 patients were eligible (having a first scan in "office hours" outside holiday periods, not due for imminent discharge, aged 18 years or more and not presenting to the Intensive Care Unit or with acute trauma). Twenty-five patients were excluded as baseline measures of renal function were missing and 132 subjects were lost to follow-up, leaving 884 study subjects. INTERVENTIONS: CT scans using high osmolality, low osmolality or no contrast (plain scan). MAIN OUTCOME MEASURE: Renal impairment as defined by a maximal increase in the serum creatinine level of greater than or equal to 50% or greater than 0.04 mmol/L from the baseline level on at least one of the subsequent four days. RESULTS: Renal impairment was seen in 4% (12 of 292), 12% (23 of 187) and 4% (16 of 405) of patients given high osmolality, low osmolality or no contrast respectively. Age and the baseline level of serum creatinine were independent predictors of the development of renal impairment (P = 0.04 and 0.02 respectively) and those given low osmolality contrast were 3.2 times (95% confidence interval, 1.6-6.3) more likely to develop renal impairment than those given no contrast. There was no excess risk with the use of high osmolality contrast compared to no contrast (odds ratio, 1.06; 95% confidence interval, 0.5-2.3). Selection factors (sicker patients being given low osmolality contrast) are likely to have accounted for the excess risk in the low osmolality group as mortality in hospital was higher in this group than in the others. The 51 patients who developed renal impairment (cases) were matched for age, sex, type of contrast and pre-existing renal impairment with up to three controls (150 patients in total). Cases were more likely to have had a blood transfusion (odds ratio, 6.40; 95% confidence interval, 2.18-22.63) or surgery (odds ratio, 3.22; 95% confidence interval, 1.19-7.65) than controls. CONCLUSIONS: Confounding by other factors which impair renal function is likely to explain previous suggestions of an effect of radio-contrast material on renal function. There does not appear to be a risk of renal impairment from the use of high osmolality radiocontrast material (although a small effect or an effect in particular subgroups cannot be excluded by our study). Fear of causing or exacerbating renal damage should not be a reason to use low osmolality contrast material, nor should it be a reason for with-holding contrast studies. PMID- 1895979 TI - Recent trends in the prescribing of cholesterol lowering drugs in Australia. A report from the Drug Utilization Subcommittee of the Pharmaceutical Benefits Advisory Committee. AB - OBJECTIVE: To determine the recent pattern of use of hypolipidaemic drugs in the Australian community. DESIGN: Drug utilisation study employing prescription data collected during the operation of the Australian Pharmaceutical Benefits Scheme (PBS). SETTING: Non-hospital drug use in Australia. PATIENTS: All patients, pensioners and non-pensioners, who received prescriptions for hypolipidaemic agents under the PBS between January 1987 and December 1989. MAIN OUTCOME MEASURES: The total number of prescriptions, average quantity dispensed with each prescription, defined daily doses (DDD) and Australian population figures for pensioners and non-pensioners were used to express the consumption of hypolipidaemic agents as DDD/1000 individuals/day. RESULTS: Between the March quarter 1987 and the December quarter 1989 prescribing of hypolipidaemics for the Australian community increased from 68,120 to 304,760 prescriptions per quarter, which translates to a rise in use from 1.2 to 5.2 DDD/1000 inhabitants/day. This included a rise in the use of clofibrate from 0.6 to 2.6 DDD/1000 inhabitants/day, and of cholestyramine from 0.6 to 1.9 DDD/1000 inhabitants/day. Prescribing of hypolipidaemics for pensioners increased from 29,569 to 123,440 prescriptions per quarter. This translated into a rise in use from 3.7 to 14.8 DDD/1000 pensioners/day. Notable rises were seen for clofibrate, 1.9 to 8.1 DDD/1000 pensioners/day, and cholestyramine, 1.6 to 4.7 DDD/1000 pensioners/day. In comparison published data from the Nordic countries and the United States showed a lower overall use of hypolipidaemics and declining consumption of clofibrate. CONCLUSIONS: The trend in Australia was unusual in that the use of clofibrate increased to a greater extent than that of the resins, cholestyramine and colestipol which are generally preferred for treatment of hypercholesterolaemia. Possible reasons for this include: the better tolerability of clofibrate; its readier availability during the study period; the recommendation by the Pharmaceutical Benefits Advisory Committee that clofibrate was the preferred drug when triglyceride levels were also elevated and the limited availability of newer hypolipidaemic agents. PMID- 1895980 TI - Disorders of movement and behaviour during sleep. AB - OBJECTIVE: To outline recently described movement disorders during sleep which are common and poorly recognised. DATA SOURCES: Computer-based literature search up to July 1990 (with the index terms sleep disorders, sleep myoclonus, nocturnal myoclonus, periodic movements in sleep, REM behaviour disorder and parasomnias) supplemented by a manual search through the references of papers obtained by computer search and a manual search through contents of the following journals: Sleep, Sleep Research, Neurology and Brain. DATA SYNTHESIS AND CONCLUSION: There is a group of common and poorly recognised movement disorders during sleep. The patient usually presents complaining of disturbed sleep, daytime somnolence and abnormal nocturnal behaviour. These conditions are susceptible to precise diagnosis and effective treatment. PMID- 1895981 TI - Incident reporting. PMID- 1895982 TI - Contralateral hemiplegia following thoracic herpes zoster. AB - OBJECTIVE: To suggest interim therapeutic guidelines for stroke following truncal herpes zoster on the basis of the first reported Australian case, in a patient who showed good clinical response related temporally to antiviral therapy. CLINICAL FEATURES: A 70-year-old patient with no known underlying immune disorder presented with left-sided hemiplegia one week after right-sided truncal herpes zoster. In all probability the neurological deficit was due to large artery vasculopathy with thrombosis. INTERVENTION AND OUTCOME: Clinical improvement (not to pre-morbid levels) was noted soon after commencement of antiviral therapy with acyclovir. CONCLUSION: Stroke following herpes zoster may be a treatable condition. In view of the previously described occurrence of viral antigen within the walls of intracerebral vessels, the occasional progression of the syndrome over months, the generally low toxicity of acyclovir and the clinical response of the few patients treated with antiviral agents to date, early antiviral therapy in patients presenting with delayed contralateral hemiplegia associated with herpes zoster is recommended as prudent. PMID- 1895983 TI - Short incubation HIV tests. PMID- 1895984 TI - The war against drugs. PMID- 1895985 TI - Endometrial ablation or hysterectomy? PMID- 1895986 TI - Long way from my country--Aboriginal patients in hospital. PMID- 1895987 TI - Our nursing homes. PMID- 1895988 TI - Vega testing in the diagnosis of allergic conditions. PMID- 1895989 TI - Hormone replacement therapy and the menopause. PMID- 1895990 TI - Global warming, ecological disruption and human health. PMID- 1895991 TI - Recertification of specialists. PMID- 1895992 TI - Estazolam--a new benzodiazepine hypnotic. PMID- 1895993 TI - Sinemet CR for Parkinson's disease. PMID- 1895994 TI - [Excusatio non petita accusatio manifesta (An unprovoked excuse is an obvious accusation)]. PMID- 1895995 TI - [The role of Langerhans cells in periodontal disease]. AB - Following a morphological description of Langerhans cells, the paper analyses their functional activity both as phagocytic cells and as antigen-presenting cells. The role of this cell population in periodontal disease is the examined in the light of recently reported findings. PMID- 1895996 TI - [The role of phagocytic cells in periodontal disease]. AB - Having described the morphological and functional characteristics of phagocytic cells, the paper underlines that, in addition to the etiological responsibility of bacterial plaque, the main role in the onset and evolution of periodontitis is played by the host's response. Phagocytic response plays a fundamental role in the host's defence reaction and represents the first barrier to the penetration of bacteria into periodontal tissue. In addition to their defensive role, phagocytic cells may also be responsible for damage to periodontal tissue as a collateral effect of their phagocytic function, thus worsening the periodontal lesion. PMID- 1895997 TI - [The direct and indirect tissue-damaging action of periodontally pathogenic bacteria]. AB - The paper describes the aggregation mechanism of bacterial plaque to the acquired film and analyses the method with which bacteria adheres to periodontal tissues, before examining the direct and indirect histolesive capacity of periodontopathogenic bacteria. PMID- 1895998 TI - [The role of LGL cells (NK and K) in periodontal disease]. AB - The paper reports the morphological and functional aspects of NK and K cells in the light of the most recent advances in the field, and pays particular attention to their cytotoxic and suppressor capacities. The role of NK and K cells in periodontal disease is then described and it is observed how this cell population is absent in healthy gums, whereas it is found with increasing frequency at disease reaches the chronic stage. The presence of LGL cells is therefore thought to be associated with the development of plaque-induced inflammation. PMID- 1895999 TI - [A histological study of the meniscal insertion of the external pterygoid muscle]. AB - The paper reports a study of the relationship between the upper head of the pterygoid muscle and the temporomandibular joint disc. Using optical microscopy, TMJ serial sections of 10 human embryos and fetuses aged from 6 to 22 weeks were examined. From the observation of serial sections, it appears that from the start of histogenesis the lateral pterygoid muscle is in contact with the condylar blastema and later with the disc and the condyle. A fibrous attachment was detected between the muscle tendon and the meniscus, and oxytalan and elastic fibres were observed near this attachment. PMID- 1896000 TI - [A comparative experimental study on the bonding resistance to horizontal traction under progressive loading between a self-polymerizing composite (Right On) and a photopolymerizing composite (Transbond)]. AB - The paper examines the bond resistance between the orthodontic clamp and tooth enamel using two different compounds: an autopolymerizing type (Right-On), already widely used in orthodontal practice, and a photopolymerizing type (Transbond) which has been recently introduced into the market. The bond was tested by applying horizontal traction with a progressively increasing weight. The results obtained were compared for statistical significance (Student's t test). PMID- 1896001 TI - [Dental alloys containing germanium. The tissue response to subcutaneous implantation]. PMID- 1896002 TI - [The creation of a functional obturator plate by a direct method in the neonatal orthodontic treatment of cheilopalatoschisis]. AB - The paper describes a simple direct method for the preparation of a functional filling plate in the neonatal orthopedic treatment of cleft palate harelip. This method allows the corrective plate to be realised so as to reproduce the complex deformed anatomical structure in the smallest detail, thus avoiding the major problems of acceptance, function and load distribution on the delicate neonatal mucosa. PMID- 1896003 TI - [An epidemiological study on dental-periodontal pathology in a sample of the school-age population of the city of Naples. I. Periodontal pathology]. AB - The paper reports the results of a study of the prevalence of periodontal diseases found in a sample group, aged between 6 and 18, resident in Naples. The structure of the survey, the clinical methods of collecting data and the statistical processing of data were carried out according to WHO directives regarding the study of oral pathologies. PMID- 1896004 TI - [An epidemiological study on dental-periodontal pathology in a sample of the school-age population of the city of Naples. II. Prevention and periodontal therapy]. AB - The need for periodontal prevention and therapy was quantified according to the prevention of pathologies within the framework of an epidemiological study carried out on a sample population aged between 6 and 18 years. Data were collected using the CPITN method (WHO). PMID- 1896005 TI - [The clinical efficacy of roxithromycin in patients with acute odontogenic infections]. AB - The clinical efficacy of a macrolide antibiotic, roxithromycin, was evaluated in 24 patients affected by acute odontogenic infections. Patients were treated with a first dose of 300 mg p.o. which was followed by 150 mg p.o. 12-hourly for the following two days. Total responses were evaluated by an arbitrary scale. The results showed that an excellent and good response was obtained in 99.96% of treated patients. On the basis of clinically compared data and the drug safety it may be concluded that roxithromycin can be successfully used in the treatment of odontogenic infections. PMID- 1896006 TI - Update: self-induced malaria associated with malariotherapy for Lyme disease- Texas. AB - In December 1990, the Texas Department of Health (TDH) was contacted by a man who had recently moved from the northeastern United States and who was considering malariotherapy for Lyme disease (LD). He described a 2-year history of unsuccessful treatment with multiple antibiotics for arthralgias and palpitations, which had been diagnosed as LD. PMID- 1896007 TI - Characterization and sequence of a novel nitrate reductase from barley. AB - Barley (Hordeum vulgare L.) has both NADH-specific and NAD(P)H-bispecific nitrate reductases. Genomic and cDNA clones of the NADH nitrate reductase have been sequenced. In this study, a genomic clone (pMJ4.1) of a second type of nitrate reductase was isolated from barley by homology to a partial-length NADH nitrate reductase cDNA and the sequence determined. The open reading frame encodes a polypeptide of 891 amino acids and its interrupted by two small introns. The deduced amino acid sequence has 70% identity to the barley NADH-specific nitrate reductase. The non-coding regions of the pMJ4.1 gene have low homology (ca. 40%) to the corresponding regions of the NADH nitrate reductase gene. Expression of the pMJ4.1 nitrate reductase gene is induced by nitrate in root tissues which corresponds to the induction of NAD(P)H nitrate reductase activity. The pMJ4.1 nitrate reductase gene is sufficiently different from all previously reported higher plant nitrate reductase genes to suggest that it encodes the barley NAD(P)H-bispecific nitrate reductase. PMID- 1896008 TI - Repair of 8-methoxypsoralen photoinduced cross-links in yeast. Analysis by alkaline step-elution and electron microscopy. AB - The repair of interstrand cross-links induced by 8-methoxypsoralen plus UVA (365 nm) radiation DNA was analyzed in diploid strains of the yeast Saccharomyces cerevisiae. The strains employed were the wild-type D7 and derivatives homozygous for the rad18-1 or the rad3-12 mutation. Alkaline step-elution and electron microscopy were performed to follow the process of induction and removal of photoinduced cross-links. In accordance with previous reports, the D7 rad3-12 strain failed to remove the induced lesions and could not incise cross-links. The strain D7 rad18-1 was nearly as efficient in the removal of 8-MOP photoadducts after 2 h of post-treatment incubation as the D7 RAD+ wild-type strain. However, as demonstrated by alkaline step-elution and electron microscopic analysis, the first incision step at DNA cross-links was three times more effective in D7 rad18 1 than in D7 RAD+. This is consistent with the hypothesis that the RAD18 gene product is involved in the filling of gaps resulting from persistent non informational DNA lesions generated by the endonucleolytic processing of DNA cross-links. Absence of this gene product may lead to extensive strand breakage and decreased recognition of such lesions by structural repair systems. PMID- 1896009 TI - Isolation of Bradyrhizobium japonicum DNA sequences that are transcribed at high levels in bacteroids. AB - DNA sequences have been isolated that are expressed at high levels in bacteroids, the differentiated form of the soybean microsymbiont, Bradyrhizobium japonicum. Random-primed cDNA was synthesized using total RNA isolated from purified B. japonicum bacteroids or from cells grown in culture. When used directly to screen bacteriophage lambda libraries, these cDNA probes produced a high background hybridization signal due to sequence similarity between B. japonicum and E. coli ribosomal DNA (rDNA) operons. To reduce this background signal, the rDNA operon of B. japonicum was cloned and the rDNA plasmid DNA used in subtractive hybridization with the cDNA probes and as a competitor in hybridization solutions. This method greatly reduced the background signal in screening of genomic libraries and thus permitted the identification of twelve unique recombinant phage which contained sequences that are expressed at higher levels in B. japonicum bacteroids than in cells grown in culture. PMID- 1896010 TI - Mutants of Nicotiana plumbaginifolia with specific resistance to auxin. AB - We have isolated nine independent auxin-resistant mutants of Nicotiana plumbaginifolia by culturing M2 seedlings in the presence of indole-3-acetic acid ethyl ester or 1-naphthaleneacetic acid at concentrations which significantly inhibit hypocotyl elongation of the wild type. The mutations were induced by treating seed with ethyl methanesulphonate and were found in the course of screening 10,000 individual M2 families. Auxin resistance was in all cases the result of a mutation at a single, nuclear locus. The dominance relationships of two of the mutants could be defined as recessive or dominant; all other mutants showed partial dominance. In contrast to previously described mutants of Arabidopsis and N. plumbaginifolia, all of the present mutants were specifically resistant to auxin; the mutants were cross-resistant to several auxins, but showed no increased resistance to cytokinin, abscisic acid, ethylene or 1-amino cyclopropane-1-carboxylic acid. The importance of the choice of the selection criterion for the isolation of specific resistance traits is discussed. PMID- 1896012 TI - Isolation and genetic analysis of a mutation that suppresses the auxotrophies of superoxide dismutase-deficient Escherichia coli K12. AB - The most striking phenotype associated with superoxide dismutase (SOD) deficiency in Escherichia coli is the inability to grow in aerobic minimal medium, which is due to the sensitivity of several amino acid biosynthetic pathways to superoxide. We have isolated two classes of pseudorevertants that grow on minimal medium at modest rates. Of these, the class that exhibited the faster growth carries mutations at a single locus, denoted ssa, which was mapped to 4 min on the E. coli chromosome. This class constituted the majority of the spontaneous pseudorevertants that were selected by the transfer of independent SOD-deficient cultures in minimal medium from anaerobic to aerobic growth conditions. Pseudoreversion at ssa suppressed requirements for a variety of unrelated amino acid supplements. Further, the SOD-deficient strains were unable to assimilate diaminopimelic acid from the growth medium, whereas the ssa pseudorevertants did so. The viability of these pseudorevertants indicates that superoxide-sensitive biosynthetic enzymes do retain some function in SOD-deficient cells during aerobic growth. PMID- 1896011 TI - A phosphoglucose isomerase gene is involved in the Rag phenotype of the yeast Kluyveromyces lactis. AB - The rag2 mutant of Kluyveromyces lactis cannot grow on glucose when mitochondrial functions are blocked by various mitochondrial inhibitors, suggesting the presence of a defect in the fermentation pathway. The RAG2 gene has been cloned from a K. lactis genomic library by complementation of the rag2 mutation. The amino acid sequence of the RAG2 protein deduced from the nucleotide sequence of the cloned RAG2 gene shows homology to the sequences of known phosphoglucose isomerases (PGI and PHI). In vivo complementation of the pgi1 mutation in Saccharomyces cerevisiae by the cloned RAG2 gene, together with measurements of specific PGI activities and the detection of PGI proteins, confirm that the RAG2 gene of K. lactis codes for the phosphoglucose isomerase enzyme. Complete loss of PGI activity observed when the coding sequence of RAG2 was disrupted leads us to conclude that RAG2 is the only gene that codes for phosphoglucose isomerase in K. lactis. The RAG2 gene of K. lactis is expressed constitutively, independently of the growth substrates (glycolytic or gluconeogenic). Unlike the pgi1 mutants of S. cerevisiae, the K. lactis rag2 mutants can still grow on glucose, however they do not produce ethanol. PMID- 1896013 TI - The superoperonal organization of genes for pigment biosynthesis and reaction center proteins is a conserved feature in Rhodobacter capsulatus: analysis of overlapping bchB and puhA transcripts. AB - Most of the essential biosynthetic and structural genes involved in bacterial photosynthesis are clustered in a 46 kb region of the Rhodobacter capsulatus genome. Previous analyses have demonstrated that the puf operon, which encodes light harvesting and reaction center structural genes as well as a regulatory gene for bacteriochlorophyll biosynthesis, is expressed from a complex set of overlapping transcripts. Differential initiation and processing of these transcripts is thought to be involved in regulating expression of puf-encoded genes. In this study we demonstrate that the puh operon, which is located 39 kb away from the puf operon, also contains overlapping transcripts. One large 11 kb puhA transcript is shown to be a product of read-through from an upstream operon (bchB) which encodes numerous bacteriochlorophyll biosynthesis genes. A second 1.1 kb mRNA is shown to be derived from the 11 kb bchB transcript by processing and a third, highly expressed, 0.95 kb transcript is shown to be initiated from a promoter located within the distal gene of the bchB operon. The occurrence of overlapping transcripts for the puf and puh operons was further shown to influence development of the photochemical apparatus during conditions of environmental shifts in oxygen tension. Evidence for the occurrence of a "superoperonal" organization of overlapping operons in several different species of purple photosynthetic bacteria is discussed. PMID- 1896014 TI - Assignment of ten DNA repair genes from Schizosaccharomyces pombe to chromosomal NotI restriction fragments. AB - Ten DNA repair (rad) genes from the fission yeast, Schizosaccharomyces pombe were mapped to the 17 NotI fragments of the three chromosomes. Nine of the genes map to chromosome I, but there is no evidence for significant clustering. PMID- 1896015 TI - Organization and expression of the two homologous genes encoding the NADP-malate dehydrogenase in Sorghum vulgare leaves. AB - We previously described the isolation and the nucleotide sequence of a nuclear gene from sorghum (NMDHI; 4.6 kb) encoding the NADP-malate dehydrogenase. Further analysis led us to identify a second homologous gene (NMDH II; 4.8 kb) located within the same 12.3 kb genomic clone (lambda LM17); these two genes are tandemly organized, in direct orientation. This second gene was entirely sequenced and comparison with the first gene showed that the positions on the 14 exons and 13 introns are conserved in both genes. The analysis of the genomic organization and copy number in the Sorghum vulgare genome revealed that there are no additional homologues and there is only one copy each of NMDH I and NMDH II. The isolation of two different cDNA clones in a previous work suggested that both genes were probably expressed. Analysis of specific mRNA accumulation during the greening process using synthetic oligonucleotide probes showed that the NMDH I gene is induced in the presence of light while the NMDH II gene seems to be constitutively expressed at low level. PMID- 1896016 TI - Tests for parental imprinting in the nematode Caenorhabditis elegans. AB - The mutation him-6 (e1423) leads to generalized chromosomal nondisjunction during meiosis in oogenesis and spermatogenesis of C. elegans. As a result, gametes nullisomic or disomic for each of the six chromosomes occur at appreciable frequency. Crosses utilizing marked him-6 strains were used to generate and identify exceptional euploid progeny which had received both homologues of a marked autosome either from the male parent or from the female parent. Examples of all ten possible exceptions were identified and found to be viable and fertile. These results (together with previous data for the X chromosome) indicate that major chromosomal imprinting effects do not occur during gametogenesis in this organism. PMID- 1896018 TI - Structural and functional analysis of the rcsA gene from Erwinia stewartii. AB - RcsA is a positive regulator of genes for extracellular polysaccharide biosynthesis in the Enterobacteriaceae. The nucleotide sequence of the rcsA gene from Erwinia stewartii was determined and compared to rcsA sequences from E. amylovora, Escherichia coli, and Klebsiella pneumoniae. Three highly conserved regions of the gene were identified. The C-terminal end of the open reading frame (ORF) shared significant amino acid homology to the LuxR class of bacterial activator proteins. Insertion and deletion mutagenesis of the 5' non-coding region indicated that maximal expression of rcsA was dependent upon cis-acting regulatory sequences located more than 300 bp upstream of the translational start site. PMID- 1896017 TI - Isolation, characterisation and molecular cloning of new mutant alleles of the fission yeast p34cdc2+ protein kinase gene: identification of temperature sensitive G2-arresting alleles. AB - The protein serine-threonine kinase p34cdc2+ plays a central role in the control of the mitotic cell cycle of the fission yeast Schizosaccharomyces pombe. p34cdc2+ function is required both for the initiation of DNA replication and for entry into mitosis, and is also required for the initiation of the second meiotic nuclear division. Recent extensive analysis of p34cdc2+ homologue proteins in higher eukaryotes has demonstrated that p34cdc2+ function is likely to be conserved in all eukaryotic cells. Here we report the isolation and characterisation of five new temperature-sensitive alleles of the cdc2+ gene. All five have been cloned and sequenced, together with the meiotically defective cdc2 N22 allele, bringing the total of p34cdc2+ mutants cloned in this and previous reports to seventeen. The five temperature-sensitive alleles define four separate mutations within the p34cdc2+ protein sequence, two of which give rise to cell cycle arrest in G2 only, when shifted to the restrictive temperature. The nature of the mutation in each protein is described and possible implications for the structure and function of p34cdc2+ discussed. PMID- 1896019 TI - Molecular characterization and genetic origin of the Brassica napus acetohydroxyacid synthase multigene family. AB - The Brassica napus rapeseed cultivar Topas contains an acetohydroxyacid synthase (AHAS) multigene family consisting of five members (AHAS 1-5). DNA sequence analysis indicate that AHAS1 and AHAS3 share extensive homology. They probably encode the AHAS enzymes essential for plant growth and development. AHAS2 has diverged significantly from AHAS1 and AHAS3 and has unique features in the coding region of the mature polypeptide, transit peptide and upstream non-coding DNA, which raises the possibility that it has a distinct function. AHAS4 and AHAS5 have interrupted coding regions and may be defective. The complexity of the AHAS multigene family in the allotetraploid species B. napus is much greater than reported for Arabidopsis thaliana and Nicotiana tabacum. Analysis of the presumptive progenitor diploid species B. campestris and B. oleracea indicated that AHAS2, AHAS3 and AHAS4 originate from the A genome, whereas AHAS1 and AHAS5 originate from the C genome. Further variation within each of the AHAS genes in these species was found. PMID- 1896020 TI - Relationship between tryptophan biosynthesis and indole-3-acetic acid production in Azospirillum: identification and sequencing of a trpGDC cluster. AB - Screening the tryptophan (Trp)-dependent indole-3-acetic acid (IAA) production of different Azospirillum species revealed that A. irakense KA3 released 10 times less IAA into the medium than A. brasilense Sp7. A cosmid library of strain Sp7 was transferred into A. irakense KA3 with the aim of characterizing genes involved in IAA biosynthesis. Trp-dependent IAA production was increased in two transconjugants which both contained an identical 18.5 kb HindIII fragment from Sp7. After Tn5 mutagenesis, cosmids carrying Tn5 insertions at 36 different positions of the 18.5 kb fragment were isolated and transferred into strain KA3. IAA production by the recipient strains was screened by HPLC. The Tn5 insertions of 4 clones with decreased IAA production were mapped on a 2 kb SalI-SphI fragment. Recombination of Tn5 insertions at this locus into the genome of strain Sp7 led to Trp auxotrophic mutants. A 5.2 kb EcoRI-SalI fragment including the 2 kb SalI-SphI fragment was sequenced and six open reading frames were identified. Three of them were clustered and their deduced amino acid sequences showed significant similarity to TrpG, TrpD and TrpC, which are enzymes involved in tryptophan biosynthesis. One of the remaining open reading frames probably encodes an acetyltransferase. The region responsible for the enhanced Trp dependent IAA production in strain KA3 corresponded to trpD, coding for the phosphoribosyl anthranilate transferase. PMID- 1896021 TI - A genetic and physiological analysis of late flowering mutants in Arabidopsis thaliana. AB - Monogenic mutants of the early ecotype Landsberg erecta were selected on the basis of late flowering under long day (LD) conditions after treatment with ethyl methanesulphonate or irradiation. In addition to later flowering the number of rosette and cauline leaves is proportionally higher in all mutants, although the correlation coefficient between the two parameters is not the same for all genotypes. Forty-two independently induced mutants were found to represent mutations at 11 loci. The mutations were either recessive, intermediate (co locus) or almost completely dominant (fwa locus). The loci are located at distinct positions on four of the five Arabidopsis chromosomes. Recombinants carrying mutations at different loci flower later than or as late as the later parental mutant. This distinction led to the assignment of eight of the loci to three epistatic groups. In wild type, vernalization promotes flowering to a small extent. For mutants at the loci fca, fve, fy and fpa, vernalization has a large effect both under LD and short day (SD) conditions, whereas co, gi, fd and fwa mutants are almost completely insensitive to this treatment. SD induces later flowering except for mutants at the co and gi loci, which flower with the same number of leaves under LD and SD conditions. This differential response of the mutants to environmental factors and their subdivision into epistatic groups is discussed in relation to a causal model for floral initiation in Arabidopsis thaliana. PMID- 1896022 TI - Evolutionary conservation of the chlorophyll a/b-binding proteins: cDNAs encoding type I, II and III LHC I polypeptides from the gymnosperm Scots pine. AB - cDNAs encoding three different LHC I polypeptides (Type I, Type II and Type III) from the gymnosperm Scots pine (Pinus sylvestris L.) were isolated and sequences. Comparisons of the deduced amino acid sequences with the corresponding tomato sequences showed that all three proteins were highly conserved although less so than the LHC II proteins. The similarities between mature Scots pine and tomato Types I, II and III LHC I proteins were 80%, 87% and 85%, respectively. Two of the five His residues that are found in AXXXH sequences, which have been identified as putative chlorophyll ligands in the Type I and Type II proteins, were not conserved. The same two regions of high homology between the different LHC proteins, which have been identified in tomato, were also found in the Scots pine proteins. Within the conserved regions, the Type I and Type II proteins had the highest similarity; however, the Type II and Type III proteins also showed a similarity in the central region. The results suggest that all flowering plants (gymnosperms and angiosperms) probably have the same set of LHC polypeptides. A new nomenclature for the genes encoding LHC polypeptides (formerly cab genes) is proposed. The names lha and lhb are suggested for genes encoding LHC I and LHC II proteins, respectively, analogous to the nomenclature for the genes encoding other photosynthetic proteins. PMID- 1896023 TI - A quantitative assay to measure chromosome stability in Schizosaccharomyces pombe. AB - The fidelity of mitotic chromosome transmission in Schizosaccharomyces pombe was estimated quantitatively by using cycloheximide resistance as a means to select cells that had undergone chromosome loss or nondisjunction. We aimed to investigate the connection between recombination and mitotic chromosome stability. A number of mutants defective in mitotic recombination such as cdc17 L16, rec59-72, and rec50-25 were tested and in these an approximately ten fold elevation of mitotic haploidization rate was found compared with controls. Our data suggest that recombination is important in controlling the maintenance of chromosomes during mitosis. PMID- 1896025 TI - Characterization of angiotensin II (AT2) binding sites in R3T3 cells. AB - Binding sites for angiotensin II were found, in a line of Swiss 3T3 cells (designated as R3T3 cells), that were insensitive to Dup 753 and dithiothreitol yet were sensitive to PD 123319, making them members of the AT2 class of angiotensin II binding sites. These binding sites appeared not to be coupled to guanine nucleotide-binding proteins, and affinity labeling experiments revealed a specifically labeled protein with an apparent molecular weight of about 100,000. Treatment of cells with angiotensin II revealed no perturbation of common signaling pathways, including stimulation of phosphatidylinositol turnover, effects on levels of cAMP, tyrosine kinase activity, and release of arachidonic acid. Also, angiotensin II or PD 123319 had no effect on cell growth, mitogenesis, or hypertrophy or on mitogenesis or hypertrophy stimulated by several growth factors. These results show that the AT2 binding site is quite distinct from the AT1 site in terms of molecular weight, binding properties, and coupling to second messenger systems. Although the significance of this novel angiotensin II binding site remains obscure, the identification of cell lines selectively expressing it should greatly aid in the understanding of its regulation and function. PMID- 1896024 TI - Characterization of recA genes and recA mutants of Rhizobium meliloti and Rhizobium leguminosarum biovar viciae. AB - DNA fragments carrying the recA genes of Rhizobium meliloti and Rhizobium leguminosarum biovar viciae were isolated by complementing a UV-sensitive recA- Escherichia coli strain. Sequence analysis revealed that the coding region of the R. meliloti recA gene consists of 1044 bp coding for 348 amino acids whereas the coding region of the R. leguminosarum bv. viciae recA gene has 1053 bp specifying 351 amino acids. The R. meliloti and R. leguminosarum bv. viciae recA genes show 84.8% homology at the DNA sequence level and of 90.1% at the amino acid sequence level. recA- mutant strains of both Rhizobium species were constructed by inserting a gentamicin resistance cassette into the respective recA gene. The resulting recA mutants exhibited an increased sensitivity to UV irradiation, were impaired in their ability to perform homologous recombination and showed a slightly reduced growth rate when compared with the respective wild-type strains. The Rhizobium recA strains did not have altered symbiotic nitrogen fixation capacity. Therefore, they represent ideal candidates for release experiments with impaired strains. PMID- 1896026 TI - Polymerase chain reaction-directed identification, cloning, and quantification of human CYP2C18 mRNA. AB - Sequencing of genomic polymerase chain reaction (PCR) products synthesized using primers generated from the CYP2C8 and CYP2C9 cDNAs revealed the presence of a new CYP2C gene in the human genome. Primers specific to exons of this new gene were used to perform PCR on human liver cDNA libraries and cDNA synthesized from human liver mRNA to generate a cDNA containing a complete cytochrome P450 amino acid reading frame. This cytochrome P450 cDNA, designated CYP2C18, displayed 85% and 87% nucleotide and 77% and 81% amino acid sequence similarities, respectively, with cDNAs and proteins corresponding to CYP2C8 and CYP2C9. cDNA-directed synthesis of CYP2C18 revealed a protein with relative Mr 49,000 on sodium dodecyl sulfate-polyacrylamide gels, which is considerably less than that calculated from the deduced amino acid composition, Mr 55,747. A preferred substrate for this enzyme has not been uncovered. Levels of CYP2C8, CYP2C9, and CYP2C18 mRNAs were examined in 17 human liver specimens using a PCR-based assay. CYP2C18 mRNA was found in all livers examined, albeit at mean levels 7-8-fold lower than those of mRNAs encoding CYP2C8 and CYP2C9. Marked interindividual differences in levels of expression of all three CYP2C mRNAs were also found. PMID- 1896027 TI - Binding kinetics of quinuclidinyl benzilate and methyl-quinuclidinyl benzilate enantiomers at neuronal (M1), cardiac (M2), and pancreatic (M3) muscarinic receptors. AB - We analyzed the competition kinetics of quinuclidinyl benzilate (QNB) and QNB methiodide enantiomers on human NB-OK1 neuroblastoma (M1), rat cardiac (M2), and rat pancreas (M3) muscarinic binding sites. The association rate constants of the four drugs depended on the receptor subtype studied and were lower with pancreas (M3) (1-9 x 10(5) M-1 sec-1) than with cardiac (M2) (1-5 x 10(6) M-1 sec-1) and NB-OK1 (M1) (1-5 x 10(6) M-1 sec-1) binding sites. At each receptor subtype, we observed no significant difference between the association rate constants of the R- and S-enantiomers of either QNB or QNB methiodide. Receptor stereoselectivity, when present, was associated with differences in unlabeled drug dissociation rate constants. The dissociation rate constant varied much more than the association rate constant, when either (R)-QNB dissociation from the three subtypes (half life, 77 min to greater than 340 min; best fit, 40 days) or dissociation of the four drugs from each receptor subtype (half-lives varying from 1.4 min to 4 hr at M1 receptors, 1.1 to 77 min at M2 receptors, and 3.5 min to greater than 340 min at M3 receptors were obtained by competition kinetics analysis) was compared. PMID- 1896028 TI - Binding of the cocaine analog 2 beta-[3H] carboxymethoxy-3 beta-(4 fluorophenyl)tropane to the serotonin transporter. AB - The cocaine analog 2 beta-carboxymethoxy-3 beta-(4-fluorophenyl)-tropane (CFT) binds to platelet plasma membrane vesicles. [3H]CFT binding is blocked equally well by cocaine and imipramine. Specific (cocaine-sensitive) binding requires Na+ and is inhibited by H+ and Cl- ions. At 150 mM Na2SO4 and pH 9.5, the KD for [3H]CFT is 232 +/- 71 nM. The number of specific [3H]CFT binding sites on the membrane vesicles is equal to the number of serotonin transporters, as measured by [3H]imipramine binding. Binding of imipramine and CFT appeared to be mutually competitive. These results suggest that [3H]CFT and cocaine bind to the serotonin transporter at a site close to but distinct from the antidepressant binding site. PMID- 1896029 TI - Selective activity and cellular pharmacology of (1R-1 alpha,2 beta,3 alpha)-9 [2,3-bis(hydroxymethyl)cyclobutyl]guanine in herpesvirus-infected cells. AB - The cycloburtane nucleoside analog (1R-1 alpha,2 beta,3 alpha)-9-[2,3 bis(hydroxymethyl)cyclobutyl]guanine [(R)-BHCG or SQ 34,514] was recently synthesized and shown to be the active enantiomer of (+/-)-BHCG (SQ 33,054), a potent inhibitor of several strains of herpesviruses [J. Med. Chem 34:1415-1421 (1991); Antiviral Res. 13:41-52 (1990)]. In plaque reduction assays, (R)-BHCG was about 1000 times more active than its S-enantiomer on herpes simplex virus type I (HSV-1) and over 200 times more active against a thymidine kinase-deficient mutant HSV-1 and human cytomegalovirus (HCMV). We now show that both (R)-BHCG and (S)-BHCG are efficiently phosphorylated to their mono-, di-, and triphosphates by HSV-1-infected cells, in a manner similar to that of acyclovir [Proc. Natl. Acad. Sci. USA 74:5716-5720 (1977)]. The uptake of both enantiomers was greatly increased upon infection; however, (S)-BHCG was taken up to about twice the extent of (R)-BHCG and accumulated primarily as the mono- and diphosphates. (R) BHCG accumulated primarily as the triphosphate, and accumulation was linear with both time and added drug concentration. The triphosphate had an apparent half life of about 10 hr. Metabolic studies using HCMV-infected cells showed only a small degree of phosphorylation of (R)-BHCG and none of (S)-BHCG. When cells were labeled with 25 microM (R)-BHCG, the amount of (R)-BHCG triphosphate formed was less than 0.5 pmol/10(6) cells. Interestingly, the ED50 value of (R)-BHCG is about 100-fold higher against HCMV than against HSV-1, and the relative levels of (R)-BHCG triphosphate formed in cells infected by the two viruses are roughly proportional to the antiviral activities. PMID- 1896030 TI - Mechanisms for the modulation of alkylating activity by the quinone group in quinone alkylating agents. AB - Previous studies have demonstrated that the quinone group may play an important role in modulating the alkylating activity of quinone alkylating agents. Introduction of a quinone moiety markedly increased the alkylating activity and cytotoxic activity of the model quinone alkylating agents benzoquinone mustard and benzoquinone dimustard. However, the cytotoxic and DNA-damaging activity of benzoquinone mustard was considerably greater than that of benzoquinone dimustard. In this study, we have investigated the role of the quinone group as a modulator of alkylating activity in these antitumor agents, using extracellular assays to eliminate differences due to cellular drug uptake and metabolism. Evidence was obtained that the alkylating activities of both benzoquinone mustard and benzoquinone dimustard were enhanced by reduction of the quinone group. In addition, when these agents were reduced, they displayed equal alkylating activity. This finding suggests that the difference in the activity of these agents in cells is not due to intrinsic differences in alkylating activities of the activated forms of these agents. Electrochemical studies revealed that benzoquinone dimustard has a lower redox potential than benzoquinone mustard and, thus, is less easily reduced. Inactivation and spectroscopic studies suggested that a major reason for the differences in activity between benzoquinone mustard and benzoquinone dimustard may be the rapid inactivation of the dimustard before its reduction. This effect may be enhanced by the lower redox potential of benzoquinone dimustard, compared with benzoquinone mustard. These findings support the hypothesis that the quinone group can modulate the alkylating activity of quinone alkylating agents; however, the mechanisms by which this modulation occurs may vary for different antitumor agents. PMID- 1896031 TI - [Site-directed mutagenesis in the uracil-repair system. Preparation of mutated forms of human alpha 2 interferon]. AB - The mutant forms of human IFN-alpha 2 gene are obtained by oligonucleotide directed mutagenesis with the use of uracil-repair system. To intensify the process the procedure of the uracil-containing DNA template preparation is modified. It was determined that when mutagenesis is performed in the uracil repair system the yield of the process depends on the mutant DNA-strand in vitro synthesis efficiency. It is shown that the stability of the 5'-end primer template complex and the level of the endogenic primers elongation are the basis factors, that determine induction mutations. PMID- 1896032 TI - [Accessibility for water molecules and relative stability of the A- and B-forms of DNA]. AB - Accessible surface areas of DNA molecules (A- and B-forms) for different probe particle radii were calculated for poly(dA).poly(dT) and poly[d(A-T)].poly[d(A T)] sequences. The problem of different forms stability is discussed in connection with accessible surface area characteristics as well as coulombic interaction between base pairs. The coulombic interaction was shown to play an important role in sequence dependent stability of the DNA molecule. PMID- 1896033 TI - [Ef-Ts elongation factor interacts with elongation factor EF-Tu on ribosomes prior to the GTP hydrolysis stage]. AB - Methods of high-speed centrifugation and limited proteolysis were used to probe the interaction of EF-Tu with EF-Ts on the ribosome. It is shown that EF-Ts dissociates from EF-Tu only after EF-Tu-mediated GTP hydrolysis, i.e. EF-Ts within the EF-Tu.ribosome complexes in the pre-GTP-hydrolysis state co-sediments with the ribosomes and its rate of proteolysis is distinct from that of free EF Ts. Moreover, as seen from the difference in sensitivity to trypsin of ribosomal proteins L19 and L27 EF-Ts affects the interaction of EF-Tu with the ribosome. PMID- 1896034 TI - [Penetration of oligo/polynucleotides and their polyalkylating derivatives into rat cells transformed by simian adenovirus DNA]. AB - The transport regularity of the [32P]-oligo/polynucleotides and their polyalkylating derivatives into SH2 rat cells transformed with SA7 adenovirus DNA was investigated. Derivatives penetrate the SH2 cells and their distribution in the subcellular fractions are proportional to the concentration of reagent in the medium. The transport efficiency of the derivatives is inhibited sharply with cell concentration increase and practically does not depend on the action of cell metabolism inhibitors. The data obtained assumes the mechanism of the derivatives transport to be liquid endocytosis. Being distributed in the cell components the polyalkylating derivatives were accumulated by the cell nuclei up to 10(5)-10(7) molecules per nucleus. Transport efficiency is much greater in the anchored cells than in the suspended ones. Though essential dephosphorylation of the utilized substances is observed in the SH2 cells, part of them maintain native chain length and the 5'-phosphate group after 1 h incubation in nucleic acids obtained from the cell nuclei. PMID- 1896035 TI - [Molecular mechanisms of regulating mammalian sex and problems of fractionating spermatozoa]. AB - We present results of a study devoted to genetic determination and to the mechanism of primary sex differentiation in mammals. Progress is achieved in the mapping of a Y chromosome region necessary and sufficient for testis determination in man (TDF) and mouse (Tdy). We discuss a possible role in sex regulation of a recently described highly conservative locus from this region, ZFY (and similar loci within other chromosomes probably coding for Zn-binding proteins, transcription regulators) and H-Y antigen as well. We note that neither locus ZFY nor H-Y can play the role of TDF (Tdy) and that studies in this direction should be carried out. Numerous works on fractioning according to sex of spermatozoa of mammals including man are critically reviewed. Contradictory data exist in literature concerning the applicability of different approaches for this purpose: from fractioning based on different inherent mobility of different sex cells or gel-filtration, to the sorting in a flow cytometer equipped with a laser light source and a computer. However, in many cases the principle underlying this or that method of fractionation and determining the positive results, i.e. the statistically important shift of the sex ratio as compared with the initial sperm, remains unclear. It is stated that on the immunological and electrophoretic approaches might appear most promising for practical application, and in cattle-breeding as well. Modern procedures for sex testing and the fertility control of spermatozoa are also examined. PMID- 1896036 TI - [A new reaction catalyzed by Bollum's terminal deoxyribonucleotidyltransferase]. AB - The highly purified preparations of Bollum's terminal transferase from calf thymus were shown to catalyze, along with the common reaction of nucleotide addition to the 3'-terminus of an oligonucleotide primer, a "non-common" reaction between dNTP or rNTP on one hand, and various alcohols on the other hand. This reaction was carried out with ethylene glycol, glycerol, ethanol and methanol to produce substances containing one molecule of nucleotide, one molecule of alcohol and non-organic pyrophosphate. The reaction conditions are cacodylate buffer, pH 7, 2, in the presence of Mg2+ or Co2+ ions. The structure was determined for the product of the reaction between glycerol and dATP, which appeared to be 2,3 dihydroxypropyl-ether of 2'-deoxyadenosine-5'-monophosphate. PMID- 1896037 TI - [A new family of widely propagated MB1-repeats in the human genome]. AB - A new family of repeats--i.e. MB1 repeats family--the number of copies of which per a human genome constitutes a few hundreds of thousands of copies has been revealed in a human gemone by computer analysis of a noncanonical similarity of nucleic acid sequences. The numbers of that family of repeats have also been revealed in the genomes of mouse and rat, they have been identified as mirror- reflected copies--in purines and pyrimidines--of B1 repeats in the genome of mouse and the Alu repeats in the human genome. The MB1 repeats tend to remain most similar at a length of 70 b.p. They are not flanked by short repeats, neither contain poly(A) region at the 3' end, by which they differ from the repeats of the SINE family. It has been assumed that the member of the Alu repeats family and the MB1 repeats family can form a so called H-form of DNA. The mirror-reflected repeat family could have been formed by replication of parallel DNA strands. PMID- 1896038 TI - [Parallel double DNA spiral. A conformational analysis of regular spirals of poly(dA).poly(dT) with different variations of joining bases]. AB - We have performed a conformational analysis of DNA double helices poly(dA).poly(dT) with parallel directed backbone strands in heteronomic model frames. All possible models of base pairs and various mutual orientation of base pair and sugarphosphate backbones were checked. By the potential energy optimization the dihedral angles and helices parameters of stable conformations of parallel double polynucleotides were calculated. The dependences of conformational energy on the base pair structure were studied. PMID- 1896039 TI - [The effect of irradiation by a He-Ne laser and phytohemagglutinin on lymphocyte mitochondria]. AB - Electron-microscopic morphometry has been applied to study mitochondria on ultrathin sections of lymphocytes from human peripheral blood. It has been shown that the stimulation of lymphocytes by the mitogen phytohemagglutinin (PHA) 1 h causes increases in the quantity of mitochondria per cellular section (17%) as well as in the total area of mitochondria per cell section (35%), i.e. an increase in mitochondrial mass. Taking into account known facts about growth and division of mitochondria in late phases of cellular cycle, one can suppose that described above changes in mitochondria during G0----G1 transition under action of PHA belong to an early phase of biogenesis of mitochondria. In the contrary, irradiation of lymphocytes with He-Ne-laser (lambda = 632.8 nm) in dose 56 J/m2 which does not cause the G0----C1 transition, results in the increase in the number of mitochondria per cellular section (20%) but not increase in the total area of mitochondria per cell section. The last finding indicates to some modification of space configuration of the mitochondria without any changes in their mass. The increase in the quantity of mitochondria per cellular section after the irradiation could be related with the increase in electrochemical proton gradient and in phosphorylating activity of mitochondria. He-Ne-laser radiation as well as mitogen PHA cause some deaggregation of mitochondria (this is more pronounced in case of PHA) which may be related to their functional activation. PMID- 1896040 TI - [Structural-functional organization of vial proteins by a localized mutagenesis method]. PMID- 1896041 TI - [Formation of a hydrate structure in the collagen-like triple helix upon hydration]. AB - By the IR-spectroscopy method successive stages of hydrate envelope formation of the collagen-like triple-helical structure of the monodisperse synthetic polytripeptide Z-(Gly-Pro-Pro)8-OMe were studied. The multistep-type process is followed by isomorphic transitions of the triple-helical structure and by the increasing of hydrogen bond strength. PMID- 1896042 TI - [Proteins bound to satellite DNA, are present in human nuclear matrix cell preparations]. AB - The presence of protein or complex of proteins that specifically bind to human satellite 3 (HS3) was shown during investigations of the nuclear matrix. The specificity of binding of HS3 was shown by using nuclear matrix immobilized on nitrocellulose. The activity disappeared after extractions of the nuclear matrix. The presence of specific activity in low salt extract was shown by gel retardation assay with whole HS3 fragment. All the subfragments of HS3 after Sau3A restriction (1 kb, 0.36 kb, 0.41 kb) also retarded in the mixture with this protein extract. DNA-protein complexes were stable even in the presence of a 1000 fold excess of competitive DNA. These data are discussed in the frame of hypotheses about the three dimensional organization of interphase chromatin. PMID- 1896043 TI - [Isolation of ribosomal subparticles from human placenta containing intact rRNA and determination of the functional activity of the 80S ribosome]. AB - The method for isolation of human placenta ribosomal subunits containing intact rRNA has been determined. The method uses fresh unfrozen placenta. Activity of 80S ribosomes obtained via reassociation of 40S and 60S subunits in non-enzymatic poly(U)-mediated Phe-tRNAPhe binding, was near 75% (maximal [14C]Phe-tRNA(Phe) binding was 1.5 mol Phe-tRNA(Phe) per mol of 80S ribosomes). Activity of 80S ribosomes with damaged rRNA isolated from frozen placenta was 2 times lower (the maximum level of poly(U)-dependent Phe-tRNA(Phe) binding was 0.7 mol per mol of ribosomes). The activity 80S ribosomes in poly(U)-mediated synthesis of polyphenylalanine was determined by using fractionated ("ribosomeless") protein synthesising system from rabbit reticulocytes. In this system up to the 50 mol of Phe residues per mol of 80S ribosomes are incorporated in acid insoluble fraction in 1 hour, at 37 degrees C. The obtained level of [14C]phenylalanine incorporation is three times as much as the amount of Phe residues observed for the ribosomal subunits, isolated from frozen placenta. PMID- 1896044 TI - [Acidic copper-containing proteins--an intermediate link to the electron transfer stage from cytochrome b-561 to dopamine-beta-monooxygenase]. AB - The interaction of acidic copper-containing protein from the membranes of chromaffin granules has been investigated with cytochrome b-561 and dopamine-beta monooxygenase from the same source. By the use of spectral and polarographic measurements it was demonstrated that the acidic copper-containing protein acts as an electron acceptor for cytochrome b-561 and as electron donor in the reactions, catalyzed by dopamine-beta-monooxygenase. According to the data obtained the possible function of the acidic copper-containing protein in vivo on the area of electron transfer chain between cytochrome b-561 and dopamine-beta monooxygenase are discussed. The activation or inhibition of the electron transfer reactions by a variety of phospholipids, analogs of membrane lipids of chromaffin granules has been established. The experiments were performed in a model systems by the use of highly purified preparations of proteins and bilamellar liposomes and micelles, prepared from the corresponding phospholipids. PMID- 1896045 TI - [Acute tubulointerstitial nephritis and uveitis (TINU syndrome) in childhood]. AB - During the last two years we have observed three children, aged 12-15 years, who developed acute non-oliguric renal failure with concomitant uveitis. Acute interstitial nephritis with lympho-monocytic infiltrates was diagnosed in all cases by renal biopsy. While two patients went into spontaneous remission, renal function in the remaining child improved only after treatment with oral prednisone. Withdrawal of steroid medication was promptly followed by a relapse, necessitating steroid therapy for a total of 4 months. The clinical and histological findings were consonant with the so-called TINU syndrome. While the pathogenesis of this syndrome is unclear, the prognosis seems to be favorable and most cases resolve spontaneously. However, in some cases, prolonged therapy with corticosteroids may be required. PMID- 1896046 TI - [Ureaplasma urealyticum--a new problem pathogen in neonatology]. AB - Some previous studies showed that Ureaplasma urealyticum is the most common germ that appears in the birthway of pregnant women and which is also frequently found in skin swabs and secretions of newborn and premature babies. The colonization of pregnant women by Ureaplasma urealyticum makes a premature birth more likely. Another factor of risk for a premature infant is a premature rupture of membranes for more than 24 hours which also makes an infection possible. There exists an association between pulmonary infection by Ureaplasma urealyticum and the development of a bronchopulmonary dysplasia especially for premature babies. According to our observations acute exacerbations of severe pneumonia can appear even after month. An attempt of therapy of pulmonary infection should be undertaken with erythromycin, if sensitive serotypes are present. In the case of erythromycin resistance chloramphenicol can be used but only under frequent controls of blood levels. We were able to observe rapid improvements with this effective therapy. PMID- 1896047 TI - [Biotinidase deficiency. Results of neonatal screening 1985-1989 in Lower Saxony]. AB - During a five-year-period (1985-1989) 420,000 newborns in Lower Saxony, FRG, were screened for biotinidase deficiency using biotinyl-para-amino-benzoic-acid as substrate. Three newborns with profound biotinidase deficiency (activity 1.1%, 2.1%, 2.3% of mean normal activity level) were detected. Nine newborns had partial biotinidase deficiency (activity 17-26% of mean normal activity level), thus giving an incidence of 1:140,000 with profound, and 1:46,667 with partial biotinidase deficiency, respectively. The infants with profound biotinidase deficiency are treated with biotin (2 x 5 mg/day) from the 3rd, 6th and 8th week of life and have developed normally so far. The children with partial biotinidase deficiency are not treated but followed up closely. The necessity of newborn screening for biotinidase deficiency is stressed. PMID- 1896048 TI - [The diameter of the large arteries in the first 3 years of life. An echocardiography study]. AB - The diameters of the great arteries at their origin and also more distal are important parameters for deciding which operation technique should be performed in cyanotic congenital heart diseases. In 130 normal newborn and infants (age between 1 day and 3 years, with a weight of 2,2 through 20 kg) who were examined because of heart murmur diameters of main pulmonary artery, right pulmonary artery, left pulmonary artery, aortic root, ascending aortae, aortic arch, and isthmic region were measured echocardiographically. Then correlations between age and diameters, and weight and diameters were calculated. The mean diameter of ascending aorta grew from 0.84 cm through 1.4 cm, of main pulmonary artery from 0.75 cm through 1.4 cm, of right pulmonary artery from 0.43 cm through 0.86 cm, of left pulmonary artery from 0.42 cm through 0.88 cm, of aortic arch from 0.68 cm through 1.44 cm, and of isthmic region from 0.47 cm through 0.83 cm. The best correlation was found using linear functions between weight and diameters. The "growing-velocity" of ascending aorta was 0.043 cm/1 kg weight gain and 0.05 cm/1 kg weight gain for main pulmonary artery (0.033 cm/1 kg weight gain for right and 0.035 cm/1 kg weight gain for left pulmonary artery). The great arteries grow linearly within the first 3 years of life. The echocardiography was a reliable tool to calculate "growing-velocities". PMID- 1896049 TI - [Brain abnormality within the scope of a VACTERL association]. AB - We report the unusual finding of brain malformations in a male newborn with anomalies of VACTERL association. Magnetic resonance imaging revealed hypoplasia of cerebellum, pons and corpus callosum as well as kinking of diencephalon and mesencephalon. These malformations of ectodermal tissue are suggestive of a defect of morphogenesis that occurred earlier than usually postulated for VACTERL cases. They resulted in severe neurologic complications and an early death. The fact that a cousin of this patient has VACTERL anomalies without cerebral involvement indicates that variable expressivity in genetically predisposed individuals may be possible for this subgroup of VACTERL cases. PMID- 1896050 TI - [Faulty origin of the right subclavian artery from the pulmonary artery: a rare cause of subclavian steal syndrome in childhood]. AB - A congenital subclavian steal syndrome may be caused by coarctation or interruption of the aortic isthmus or by isolation of a subclavian artery. We describe a patient with D-transposition of the great arteries, a left aortic arch, and isolation of the right subclavian artery which originated from the right pulmonary artery via a right ductus arteriosus. A subclavian steal syndrome was demonstrated noninvasively by echocardiography and doppler sonography of the cerebral arteries. We recommend routine cerebral doppler sonography for all infants with congenital heart disease and unilaterally weak brachial pulses. Since the long term outcome of the congenital subclavian steal syndrome is uncertain the aberrant subclavian artery should be reimplanted at the time of corrective cardiac surgery. PMID- 1896051 TI - [Fatal poisoning caused by aconite monk's hood (Aconitum napellus)]. AB - Severe intoxications after ingestion of monk's hood are rare in childhood. We report a case of fatal intoxication in a 20 months old child. There is no specific therapy available. A review of the literature is added. PMID- 1896053 TI - Highlights of the international symposium on immunotherapeutic prospects of infectious diseases. PMID- 1896052 TI - [Encephalopathy in leukemia treatment in children]. AB - Side effects on the central nervous system by antileukemic treatment have been well known for a long time. We report on 2 patients suffering from a severe encephalopathy during antileukemic therapy. Furthermore the results of cerebral computer tomography in 50 children with acute leukemia have been analysed. In 21 patients morphological findings were evident. Four patients had CCT-changes already before the beginning of their treatment. Initially in 2 patients leukemic cerebral infiltrations were detected. The importance of the computer tomography for the detection of cerebral affections by disease and treatment is demonstrated. PMID- 1896054 TI - Mouse targets undergo double-strand DNA fragmentation when exposed to syngeneic or xenogeneic LAK cells whereas human targets undergo single-strand breaks. AB - A number of recent studies have shown that mouse target cells (TC) of hematopoietic origin, when exposed to cytotoxic lymphocytes, undergo double stranded DNA fragmentation. The cause and relevance of the fragmentation remain controversial. In this study we generated a number of mouse (M-LAK) and human LAK (H-LAK) cells and exposed them to a variety of mouse and human TC. YAC and SP/2, 2 mouse TC underwent rapid and extensive fragmentation when lysed by either human or mouse LAK whereas K562 and Daudi, 2 human TC, under the same conditions did not. All 4 TC, however, were killed quite efficiently. Next we labeled TC with 125I-deoxyuridine, exposed them to LAK cells for up to 18 h and loaded the LAK:TC mixtures over an alkaline linear sucrose gradient. After lysing the cells with a lysis buffer containing Triton X-100 we showed that K562 that had been in contact with LAK cells for more than 1 h exhibited single-strand nicks. However, whereas double-strand fragmentation preceded chromium release (lytic activity), the appearance of single-strand nicks did not. Finally, protein synthesis was not required for either type of fragmentation. In summary, we have demonstrated that: (1) the ability to undergo DNA fragmentation is a property of the TC rather than the effector cells that mediated their death, and (2) K562 and Daudi, 2 human TC, undergo single-strand nicks when lysed by LAK cells whereas SP/2 and YAC, 2 mouse TC undergo double-strand fragmentation when exposed to the same syngeneic or xenogeneic effector cells. PMID- 1896056 TI - [Use of nonradioactively labelled DNA-probes for DNA-diagnosis of Duchenne's muscular dystrophy]. AB - Routinely, we detect 0,1 pg of plasmid DNA using the nonradioactive DNA labeling and detection kit produced by Boehringer Mannheim (FRG). Using the kit we have determined the carrier status of a woman in a family with a case of Duchenne muscular dystrophy by the blot hybridization technique. PMID- 1896055 TI - [Molecular cloning of cDNA encoding human prointerleukin-6]. AB - The data are presented on the cloning and sequencing of cDNA coding for human interleukin-6. The variability of cDNA proIL-6 cloned from different cellular sources was studied. The variability of cDNA proIL-6 may be expressed as heterogeneity of 5'- and 3'-end sequences of cDNA as well as single base-pair changes. PMID- 1896057 TI - [The role of polymerase protein genes of influenza A virus in the transition from the early to late stage of replication]. AB - Regulation of influenza virus RNA replication was studied with the use of A/FPV/Rostock/34 strain ts-mutants. Mutants C44, C15, C45 possessing the ts defects in the PB2, PB1 and PA genes respectively were used for the infection of chick embryo cultured cells and H-uridine-labelled nucleocapsid-associated RNA was analysed in polyacrylamide gel electrophoresis to assess the kinetics of vRNA synthesis. A typical early-late transition of the pattern of vRNA synthesis was observed in the cells infected with C44, whereas the other two mutants exhibited a slightly changed (C15) or strongly distorted (C45) pattern. In shift up experiments after the transfer to non-permissive temperature all the mutants exhibited partial reversion to an early pattern of vRNA synthesis. The results are discussed in connection with the mechanism of the early-late transition of influenza virus-specific RNA synthesis. PMID- 1896058 TI - [Plasmid pBS195 with a wide range of hosts, isolated from lactobacilli]. AB - The nonconjugative 4.4 kb plasmid pBS195 has been found in Lactobacillus sp. 195 strain resistant to kanamycin and streptomycin. The plasmid pBS195 determining the resistance to kanamycin has a broad host range. It is inherited by the Gram positive microorganisms (Bacillus subtilis) as well as by Escherichia coli cells, has the cleavage sites for the restriction endonucleases BamHI, EcoRI, HindIII, PstI, KpnI. The restriction map of the plasmid for these enzymes is constructed. The broad host range, efficiently expressed marker, the presence of the unique restriction sites, small size make the plasmid pBS195 promising for the genetic engineering research. PMID- 1896059 TI - [Genetic properties of the nonflagellar Bacillus thuringiensis mutant]. AB - The nonflagellar mutant has been selected in Bacillus thuringiensis strain 33-69 var. galleriae. The absence of flagella in the mutant cells is confirmed by electron microscopy, by the specific "trench transit" test. The mutant preserved the biochemical characteristics of the parent strain, possesses the same phage sensitivity but lower sporulation ability. Fla+ phenotype is cotransduced with the His+ one in general transduction. PMID- 1896060 TI - [Basic factors of pathogenicity and cloning of pseudomonads]. PMID- 1896061 TI - [Complete nucleotide sequence of the Eastern equine encephalomyelitis virus genome]. AB - The complete nucleotide sequence of the genomic 42S RNA of Eastern equine encephalitis virus has been defined for the first time. The strategy of this viral genome occurred analogous to the ones of the other alfa viruses. The comparison of amino acid sequences of E1 and E2 proteins from the two strains of the virus has revealed a number of differences. Partially, they are localized in the hydrophilic regions of the protein molecules and evidently participate in organization of the specific antigenic structures. The amino acid sequences of all viral proteins have been comparatively analysed with the sequences of the analogous proteins of other known alfa viruses. PMID- 1896062 TI - Indirect costs again. PMID- 1896063 TI - AIDS scandal indicts French government. PMID- 1896064 TI - US science's 'stealth agency'. PMID- 1896065 TI - AIDS meet relocates. PMID- 1896066 TI - Imaginary hazards? PMID- 1896067 TI - OSI procedures. PMID- 1896068 TI - The invisible-obstacle race. AB - In some respects, things are getting worse, not better, for women in science. Positive measures need to be taken for progress towards genuine equality of opportunity. PMID- 1896069 TI - Cognitive neuropsychology. Writing without vowels. PMID- 1896070 TI - Coelacanth's relationships. PMID- 1896071 TI - Primary structure and expression of bovine poly(A) polymerase. AB - Poly(A) polymerase has a critical role in the synthesis of messenger RNA in eukaryotic cells. The isolation and characterization of complementary DNAs encoding bovine poly(A) polymerase is described here. The predicted sequences of the mRNA and protein reveal features that provide insights into how the enzyme functions and how it might be regulated. Poly(A) polymerase expressed from a cloned cDNA is fully functional in in vitro assays, and mutational analyses have identified a putative regulatory domain that enhances, but is not essential for, activity. PMID- 1896072 TI - A selective deficit for writing vowels in acquired dysgraphia. AB - Brain-damaged patients with acquired writing disorders provide important information about the normal processes of spelling and writing. Current models indicate that to produce a letter string, its 'abstract' representation is computed and stored in a temporary orthographic buffer, from which it is converted to a verbal code (if the word is to be spelled aloud) or to a physical letter code (if the word is to be written). The stored graphemic representations specify the identity and order of the component letters and their consonant/vowel status. Here I describe the spelling performance of two patients with a selective deficit in writing vowels. When writing words, the first patient omitted all vowels, leaving a blank space between consonants or consonant clusters, whereas the second produced errors that almost exclusively involved vowels. This pattern of performance supports the hypothesis that the consonant/vowel status of graphemes is differentially specified in the spelling process and may be selectively affected after brain damage. PMID- 1896073 TI - Identification and mapping to chromosome 1 of a susceptibility locus for periinsulitis in non-obese diabetic mice. AB - Insulin-dependent diabetes mellitus (IDDM) is a polygenic disease caused by autoimmune destruction of insulin-producing beta cells in the islets of Langerhans. Its onset is preceded by a long and variable period in which lymphoid cells infiltrate the pancreas but first remain outside the islets (peri insulitis) before invading them (insulitis). Among susceptibility loci, only the major histocompatibility complex (MHC) has been clearly assigned. Genetic study of the nonobese diabetic (NOD) mouse model for insulin-dependent diabetes mellitus has revealed genetic linkage of insulitis and of early onset diabetes with two non-MHC loci mapping to chromosome 3 and 11 respectively. Here we report a close association of periinsulitis with a third non-MHC locus mapping to chromosome 1. Successive stages in the progression of diabetic disease thus appear to be controlled by distinct genes or sets of genes. PMID- 1896074 TI - Hsp104 is a highly conserved protein with two essential nucleotide-binding sites. AB - Most eukaryotic cells produce proteins with relative molecular masses in the range of 100,000 to 110,000 after exposure to high temperatures. These proteins have been studied only in yeast and mammalian cells. In Saccharomyces cerevisiae, heat-shock protein hsp104 is vital for tolerance to heat, ethanol and other stresses. The mammalian hsp110 protein is nucleolar and redistributes with growth state, nutritional conditions and heat shock. The relationships between hsp110, hsp104 and the high molecular mass heat-shock proteins of other organisms were unknown. We report here that hsp104 is a member of the highly conserved ClpA/ClpB protein family first identified in Escherichia coli and that additional heat inducible members of this family are present in Schizosaccharomyces pombe and in mammals. Mutagenesis of two putative nucleotide-binding sites in hsp104 indicates that both are essential for function in thermotolerance. PMID- 1896075 TI - Structure of human cyclophilin and its binding site for cyclosporin A determined by X-ray crystallography and NMR spectroscopy. AB - The protein cyclophilin is the major intracellular receptor for the immunosuppressive drug cyclosporin A. Cyclosporin A acts as an inhibitor of T cell activation and can prevent graft rejection in organ and bone marrow transplantation. Cyclophilin may be responsible for mediating this immunosuppressive response. Cyclophilin also catalyses the interconversion of the cis and trans isomers of the peptidyl-prolyl amide bonds of peptide and protein substrates. Here we report the X-ray crystal structure of human recombinant cyclophilin complexed with a tetrapeptide and the identification, by nuclear magnetic resonance spectroscopy, of the specific binding site for cyclosporin A. Cyclophilin has an eight-stranded antiparallel beta-barrel structure. The prolyl isomerase substrate-binding site is coincident with the cyclosporine-binding site. These results may help to provide a structural basis for rationalizing the immunosuppressive function of the cyclosporin-cyclophilin system and will also be important in the design of improved immunosuppressant drugs. PMID- 1896076 TI - US kills sex survey. PMID- 1896077 TI - Death pills from pesticide. PMID- 1896078 TI - Problems of British science. PMID- 1896079 TI - A future for British science. PMID- 1896080 TI - NIH push for women's health. PMID- 1896081 TI - Neuropsychology. Only four possible solutions. PMID- 1896082 TI - Biocontrol risks. PMID- 1896083 TI - Coronavirus motif. PMID- 1896084 TI - Calcium binding to fibrillin? PMID- 1896085 TI - Iso-orientation domains in cat visual cortex are arranged in pinwheel-like patterns. AB - The mammalian cortex is organized in a columnar fashion: neurons lying below each other from the pia to the white matter usually share many functional properties. Across the cortical surface, cells with similar response properties are also clustered together, forming elongated bands or patches. Some response properties, such as orientation preference in the visual cortex, change gradually across the cortical surface forming 'orientation maps'. To determine the precise layout of iso-orientation domains, knowledge of responses not only to one but to many stimulus orientations is essential. Therefore, the exact depiction of orientation maps has been hampered by technical difficulties and remained controversial for almost thirty years. Here we use in vivo optical imaging based on intrinsic signals to gather information on the responses of a piece of cortex to gratings in many different orientations. This complete set of responses then provides detailed information on the structure of the orientation map in a large patch of cortex from area 18 of the cat. We find that cortical regions that respond best to one orientation form highly ordered patches rather than elongated bands. These iso-orientation patches are organized around 'orientation centres', producing pinwheel-like patterns in which the orientation preference of cells is changing continuously across the cortex. We have also analysed our data for fast changes in orientation preference and find that these 'fractures' are limited to the orientation centres. The pinwheels and orientation centres are such a prominent organizational feature that it should be important to understand their development as well as their function in the processing of visual information. PMID- 1896086 TI - Rapid spread of an inherited incompatibility factor in California Drosophila. AB - In Drosophila simulans in California, an inherited cytoplasmic incompatibility factor reduces egg hatch when infected males mate with uninfected females. The infection is spreading at a rate of more than 100 km per year; populations in which the infection was rare have become almost completely infected within three years. Analyses of the spread using estimates of selection in the field suggest dispersal distances far higher than those found by direct observation of flies. Hence, occasional long-distance dispersal, possibly coupled with local extinction and recolonization, may be important to the dynamics. Incompatibility factors that can readily spread through natural populations may be useful for population manipulation and important as a post-mating isolating mechanism. PMID- 1896087 TI - Cotranslocational insertion of apolipoprotein B into the inner leaflet of the endoplasmic reticulum. AB - Apolipoprotein (apo) B100 is required for the distribution of hepatic triglyceride to peripheral tissues as very-low-density lipoproteins. The translocation of apo B100 into the endoplasmic reticulum (ER) and its subsequent assembly into lipoprotein particles is of particular interest as the protein is both very large (relative molecular mass 512,000) and insoluble in water. It has been proposed that apo B translocation occurs in discrete stages and is completed post-translationally. Several sites of arrest of translocation were reported to be present in apo B15 (the N-terminal 15% of the protein). We have re-examined this question by in vitro translation coupled with translocation into microsomes, and find no evidence for transmembrane segments in truncated apo B proteins. Translocated apo B17 is strongly associated with the membrane of the ER, being only partially releasable with alkaline carbonate, and remaining bound to the microsomes following disruption with saponin. The efficient binding of short segments of apo B, despite the absence of transmembrane domains, suggests that apo B is cotranslationally inserted into the inner leaflet of the ER. This will obviate problems caused by the size and insolubility of apo B100, because the growing hydrophobic protein chains will never exist in a lipid-free form during translocation. From the inner leaflet, apo B in association with membrane-derived lipid can bud into the lumen of the ER to form nascent lipoprotein particles. PMID- 1896088 TI - Telomerase primer specificity and chromosome healing. AB - Chromosome healing by de novo telomere addition at nontelomeric sites has been well characterized in several organisms. The Tetrahymena telomerase ribonucleoprotein uses an internal RNA template to catalyse d(TTGGGG)n telomere addition to the 3' end of telomeric sequence in vitro and in vivo. Studies of telomerase RNA indicated that hybridization of the RNA template region, 5' CAACCCCAA-3', to the 3' end of single-stranded telomeric oligonucleotides might be important for primer recognition and utilization. The apparent requirement of telomerase for pre-existing telomeric sequence has raised questions regarding its role in chromosome healing. We report here that Tetrahymena telomerase can specifically elongate single-stranded DNA oligonucleotides whose termini are not complementary to the RNA template sequence 5'-CAACCCCAA-3'. These data suggest that telomerase may be able to heal chromosomes directly in vivo. PMID- 1896089 TI - Recognition of a chromosome truncation site associated with alpha-thalassaemia by human telomerase. AB - Telomeres define the ends of chromosomes; they consist of short tandemly repeated DNA sequences loosely conserved in eukaryotes (G1-8(T/A)1-4). Telomerase is a ribonucleoprotein which, in vitro, recognizes a single-stranded G-rich telomere primer and adds multiple telomeric repeats to its 3' end by using a template in the RNA moiety. In conjunction with other components, telomerase may balance the loss of telomeric repeats due to DNA replication. Another role of telomerase may be the de novo formation of telomeres. In eukaryotes like Tetrahymena, this process is an integral part of the formation of macronuclear chromosomes. In other eukaryotes this process stabilizes broken chromosomes. A case of human alpha-thalassaemia is caused by a truncation of chromosome 16 that has been healed by the addition of telomeric repeats (TTAGGG)n. Using an in vitro assay, I show here that human telomerase correctly recognizes the chromosome 16 breakpoint sequence and adds (TTAGGG)n repeats. The DNA sequence requirements are minimal and seem to define two modes of DNA recognition by telomerase. PMID- 1896090 TI - Uremic acquired renal cystic disease. Natural history and complications. AB - Males on long-term dialysis tend to develop more severe forms of acquired cystic disease of the kidney than females. The severity of the disease is unaffected by therapeutic modality, either hemodialysis or CAPD, however, cystic transformation becomes less extensive after successful renal transplantation. The fundamental pathological change characteristic of acquired cystic disease is epithelial hyperplasia, with the uremic milieu and duration of uremia being the most important factors in its development. Renal cell carcinoma, the most important complication of acquired renal cystic disease, has a high prevalence and incidence, usually remains symptomless and sometimes reveals metastases. Therefore, many clinicians and investigators, but not all, accept the need for regular screening of all dialysis patients for the development of renal cell carcinoma. Major complications of acquired renal cystic disease, malignancy and retroperitoneal bleeding, will become increasingly important because of the growing number of patients on long-term dialysis. PMID- 1896091 TI - Immune deficiency in uremia: interleukin-2 production and responsiveness and interleukin-2 receptor expression and release. AB - We have studied the role of interleukin-2 (IL-2) and its receptors in the impaired in vitro lymphocyte response characteristic of hemodialysis patients treated by means of cuprophane membranes. The proliferative response of T lymphocytes as well as T-cell-dependent B cell proliferation after stimulation with mitogens was significantly reduced in hemodialysis patients. The in vitro production of IL-2 after such stimulation in parallel cultures was found to be similar in patients and in controls. The expression of IL-2 receptor on the lymphocyte cellular membrane in the hemodialysis group was also similar to controls. The in vitro proliferative response of uremic lymphocytes to exogenous IL-2, however, was significantly depressed suggesting a reduced availability of biologically active IL-2 receptor. The release of soluble IL-2 receptor by lectin stimulated lymphocytes in culture was also significantly lower in the patient group; yet, hemodialysis patients has a strikingly elevated level of plasma soluble IL-2 receptor, and similar high levels were also found in three other groups of end-stage renal disease patients dialyzed by means of cellulose acetate, polysulfone and polyacrylonitrile membranes, as well as in a group of uremic patients on conservative treatment. In the hemodialysis patient group a significant positive correlation between levels of soluble IL-2 receptor and the duration of hemodialysis was found. Since soluble IL-2 receptor has been reported to down-regulate lymphocyte responses, the elevation in plasma levels of soluble IL-2 receptor in hemodialysis patients may be a pathogenetic factor in the progressive development of impaired immunity associated with end-stage renal disease. PMID- 1896093 TI - Treatment of refractory hyperparathyroidism in patients on hemodialysis by intermittent oral administration of 1,25(OH)2vitamin D3. AB - Intermittent oral administration of high dose 1,25(OH)2vitamin D3 was conducted in 7 patients associated with treatment-resistant secondary hyperparathyroidism (2nd HPT) on hemodialysis (HD) therapy. Each patient had a long history of HD therapy (range: 101-181 months, 145 +/- 29 months). Although serum calcium levels were maintained under the upper limit of the normal range with the appropriate dose of 1 alpha(OH)vitamin D3 every day before the present therapy, 2nd HPT could not have been controlled. The dose of 2-3 micrograms of 1,25(OH)2vitamin D3 3 times a week could successfully suppress serum levels of parathyroid hormone (iPTH) in all 7 patients after 20-32 weeks. The vitamin was given in the evening before each HD session and the dose and frequency of administration were dependent of the serum calcium level in each patient. After 20 weeks the iPTH-C and iPTH-intact levels decreased significantly from 35.0 +/- 15.8 to 18.6 +/- 11.7 ng/ml and from 533.2 +/- 200.0 to 249.5 +/- 136.2 pg/ml, respectively. The frequency of harmful elevations of serum calcium levels was not significantly increased in comparison with that in the previous period of the study, because serum calcium levels were strictly monitored with frequent checks. In conclusion, we could safely obtain an effect similar to the intravenous administration of the vitamin through the intermittent administration of a high oral dose 1,25(OH)2vitamin D3 in the treatment of refractory 2nd HPT in patients on HD therapy. PMID- 1896092 TI - Oral administration of 24,25(OH)2D3 suppresses the serum parathyroid hormone levels of dialysis patients. AB - We measured the serum parathyroid hormone (PTH) levels in 20 patients treated with continuous ambulatory peritoneal dialysis before and after oral treatment with 24,25-dihydroxyvitamin D3- 24,25(OH)2D3. This metabolite was given in addition to existing treatment with 1 alpha-OH-D3 and calcium carbonate. Administration of 24,25(OH)2D3 led to a significant decrease in PTH levels (intact molecule) from 382 +/- (SE) 65 to 245 +/- 54 pg/ml in 9 patients whose initial levels were extremely high (p = 0.01). No side effects were observed. On the average, calcium values were unchanged and within the normal range throughout the study period; however, a few episodes of mild asymptomatic hypercalcemia occurred which responded quickly to reduction of the calcium carbonate dosage. The present study suggests that oral administration of 24,25(OH)2D3 combined with 1 alpha-OH-D3 is safe and capable of suppressing the raised serum PTH levels of end-stage renal disease patients without the danger of significant hypercalcemia. PMID- 1896094 TI - Renal function and renal function reserve in insulin-dependent diabetic patients during (near) normoglycaemia. AB - Twenty-three normoalbuminuric (N) and 7 microalbuminuric (M) insulin-dependent diabetes mellitus (IDDM) patients were studied under (near) normoglycaemic conditions. They were reasonably well controlled during the period preceding the renal function test (HbA1: N = 7.6 +/- 1.3%, N = 8.0 +/- 2.2%; normal less than 6.0%). Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured using the clearances of 125I-thalamate and 131I-hippuran, respectively. The renal reserve filtration capacity (RRFC) was tested by using a combination of a liquid mixed meal and an amino acid infusion. Blood glucose levels were kept as constant as possible throughout the testing procedure, both under baseline (BL) conditions and after stimulation (S). Under such (near) normoglycaemic conditions, no BL GFR values exceeding 150 ml/min/1.73 m2 could be established. Furthermore, a RRFC could be established in all patients. Both groups showed a comparatively larger increase in GFR (N 13.0 +/- 3.8%, M 10.8 +/- 3.6%) than in ERPF (N 4.8 +/- 7.0%, M 2.2 +/- 5.8%; % delta GFR vs. % delta ERPF p less than 0.01), resulting in a higher filtration fraction (FF) during stimulation (N: BL FF 0.25 +/- 0.03 vs. S FF 0.27 +/- 0.03, p less than 0.01; M: BL FF 0.25 +/- 0.01 vs. S FF 0.27 +/- 0.01, p less than 0.05). This suggests afferent vasodilation during stimulation in these (near) normoglycaemic, reasonably well-controlled IDDM patients, a situation comparable to that in non diabetic subjects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1896095 TI - Recurrence of hyperparathyroidism after total parathyroidectomy with autotransplantation: a new technique to localize the source of hormone excess. AB - The diagnosis of persistent or recurrent hyperparathyroidism after total parathyroidectomy with autograft in the forearm needs a correct assessment of graft function. In 6 patients with relapsing hyperparathyroidism after total parathyroidectomy with forearm implant, total ischaemic blockade of the arm bearing the parathyroid graft, produced a 'temporal implantectomy' with reduction of iPTH in those with graft hyperfunction. In 2 patients with proved supernumerary gland, total ischaemia of the 'graft' was not followed by iPTH changes. Total ischaemic blockade of the arm bearing the parathyroid graft is a valuable method for a correct assessment of graft function. It gives useful information in order to avoid or indicate a reoperation of the neck in patients who had previously undergone parathyroidectomy. PMID- 1896096 TI - Disturbances of cerebral purine and pyrimidine metabolism in young children with chronic renal failure. AB - Chronic renal failure during childhood may be associated with delayed cognitive development. From 10 children with chronic renal failure, aged 2-59 months, plasma and cerebrospinal fluid (CSF) purines and pyrimidines have been determined. A marked increase of pseudouridine and cytidine was demonstrated in CSF of 10 and 8 children, respectively. The plasma concentration of pseudouridine was increased in a varying degree to a maximal value of more than 10 times the upper limit of normal. The plasma concentration of cytidine showed only moderately elevated values. In 3 children the study of CSF and plasma was repeated 6 weeks after the start of continuous ambulatory peritoneal dialysis. The abnormal concentrations of pseudouridine and cytidine were still present in CSF and plasma. Further studies are necessary to elucidate the cause of this unknown biochemical aberration of the central nervous system. PMID- 1896097 TI - Idiopathic membranous nephropathy, associated with HLA-DRw3 and not related to monocyte-phagocyte system Fc receptor dysfunction, in father and son. AB - Familial idiopathic membranous nephropathy, an immune-complex-associated glomerulopathy, has not been previously reported in father and son, despite its striking immunogenetic correlation, especially with HLA-DR3. As a dysfunction of the monocyte-phagocyte system (MPS), it has been observed linked to DR3 antigen, so we studied the MPS Fc receptor function in a father and his son with a histologically proven membranous nephropathy, associated with the haplotype A9 B35-DR3-DQw2. The Fc receptor function of the MPS was examined by measuring the clearance of IgG-sensitized, 51Cr-labeled erythrocytes and by measuring the ability of isolated monocytes to ingest autologous red blood cells coated with IgG anti-Rh (D) antibody. Immune clearance and in vitro phagocytosis was normal in both patients and not related to their levels of immune complexes (as measured by ELISA C1q and Conglutinin solid-phase binding assay). This report suggest that genetic factors may play an important role in the development of membranous nephropathy, and it seems not to be related to a dysfunction of MPS as measured by these tests. PMID- 1896098 TI - 'Spontaneous'/uremic hypoglycemia is not a distinct entity: substantiation from a literature review. AB - A review of the literature on 'spontaneous'/uremic hypoglycemia reveals that in only 4 of 36 cases is there no clear explanation for the low blood glucose. In all other cases there were factors in addition to chronic renal failure that could have accounted for hypoglycemia. These factors included states of malnutrition, drugs, and other illnesses. We propose that there is no merit in the term 'spontaneous' hypoglycemia, and that the multifactorial nature of uremic hypoglycemia should be appreciated. PMID- 1896099 TI - Blood pressure in unilaterally nephrectomized rabbits: a correlation with serum renotropic activity. AB - Over 40 years ago, Grollman reported that unilateral nephrectomy (UN) in rabbits precipitated hypertension and suggested that liberation of a pressor substance by an ischemic or damaged kidney could not be causative. Because others were unable to corroborate that UN in rabbits led to increased blood pressure (BP), we followed 7 rabbits after UN and 4 rabbits after a sham operation. At 7-10 days postoperatively, BP increased from the baseline average of 83 to an average of 97 mm Hg in the UN rabbits (p less than 0.01). In contrast, BP did not change significantly after sham operation. Measurements of blood chemistries, serum insulin levels and digoxin-like substances showed no significant changes after UN which would explain the BP rise, but plasma renin activity (PRA) rose from 11.4 to 30.3 ng/ml/h, (p less than 0.05). However, similar elevations occurred in sham operated rabbits that showed no significant change in BP, i.e. 10.6-26.2 ng/ml/h. Measurement of serum renotropic activity after UN, but not after sham operation, also showed a significant elevation above baseline 97.6% (p less than 0.001). The renotropic activity 7-10 days after UN unlike PRA correlated significantly with the changes in BP (r = 0.87, p less than 0.001). We conclude that BP rises after UN in rabbits, confirming Grollman's findings. The correlative rise in BP and serum renotropic activity may play an important role in the BP elevation after UN. PMID- 1896100 TI - Case report of amyloidosis-like glomerulopathy with hepatic involvement. AB - A few cases of nephrotic syndrome with the glomerular deposition of an amyloid like material which did not stain with Congo red have been documented. But extrarenal deposits have not been previously reported in this disease. We describe here a case of nephrotic syndrome associated with the deposition of an amyloid-like material in the liver as well as in the renal glomeruli. The deposits were made up of fibrillar structures which resembled those of amyloid when viewed through the electron microscope but they did not stain with Congo red. This is the first report of amyloidosis-like glomerulopathy with extrarenal deposits. PMID- 1896101 TI - Renal cell carcinoma of the native kidney after renal transplantation. A case report and review of the literature. AB - We report a patient with small renal cell carcinoma of the native kidney long after renal transplantation, which was considered to have developed before transplantation, and review the characteristics of renal cell carcinoma and acquired cystic disease following transplantation. PMID- 1896102 TI - Increased risk of central nervous system toxicity in patients treated with ciclosporin and imipenem/cilastatin. PMID- 1896103 TI - Factor XIII deficiency in adult polycystic kidney disease. PMID- 1896105 TI - A novel treatment for idiopathic oedema of women. PMID- 1896104 TI - Breathing of uremic rats. PMID- 1896106 TI - Hypertension in chronic renal failure. PMID- 1896107 TI - Is testing with dDAVP useful in detecting carriers of the nephrogenic diabetes insipidus gene? PMID- 1896108 TI - Decreased blood pressure after a year of erythropoietin. PMID- 1896109 TI - Helicobacter pylori infection in uraemic patients. PMID- 1896110 TI - Cyclophosphamide pulse therapy in relapsing nephrotic syndrome. PMID- 1896111 TI - Charcoal hemoperfusion and methotrexate toxicity. PMID- 1896112 TI - Genetic counselling in adult polycystic kidney disease. PMID- 1896113 TI - Muscle cramps and creatine kinase elevations in hemodialysis patients. PMID- 1896114 TI - Drugs potentiating cyclosporin nephrotoxicity. PMID- 1896115 TI - [Hemorrhagic type of moyamoya disease]. AB - Clinical picture of Moya Moya Disease was analyzed in 18 cases. In 16 cases whose CT scan were available at the time of the first bleeding, hematoma at the basal ganglia was noted in 43.8%, primary ventricular hemorrhage in 37.5%, thalamic hemorrhage with ventricular rupture in 12.5% and subcortical hemorrhage in 6.3%. The frequencies shown above were well correlated to previous reports. In MRI performed 1 year or more after primary ventricular hemorrhage, the primary bleeding site was demonstrated at the lateral wall of the lateral ventricle, in proton weighted and T2 weighted images. MRI can detect the site of old bleeding points and its chronological change if the study is repeated. In a follow-up period of 5.4 years, 27.8% of the cases had rebleeding one or more times. As a result, good outcome was noted in 72.2% after the 1st bleeding, and in 55.6% after re-bleedings. Death occurred in 5.6% of patients after the 1st bleeding and in 22.2% after further rebleeding. Rebleeding worsened the outcome. Therefore, prevention of rebleeding is important. From a therapeutic viewpoint, although a direct relation between rebleeding and untreated hypertension could not be established, blood pressure control is critical at both the acute and the chronic stages. Reconstructive vascular surgery is a recommendable method for properly selected patients. PMID- 1896116 TI - [Clinical significance of thrombocytopenia associated with hemorrhagic cerebrovascular diseases]. AB - We investigated the clinical significance of thrombocytopenia (platelet counts less than 10 x 10(4)/mm3) associated with hemorrhagic cerebrovascular disease. This study was conducted in 96 patients suffering from hemorrhagic cerebrovascular diseases. We divided the clinical course into 3 stages: acute (from the 1st to 7th day), subacute (8th-21st day) and chronic (after the 22nd day). The average age of the patients with thrombocytopenia (TCP) was 60.6 years old. TCP was more frequent in men (81.3%) than in women (18.7%). TCP developed in 18.6% (8/43) of patients with subarachnoid hemorrhage (SAH) and in 15.1% (8/53) of those with intracerebral hemorrhage (ICH). Among the patients with SAH, four were in the acute stage, three in the subacute stage and two in the chronic stage. TCP due to SAH was more likely to develop in the acute and/or subacute stage. TCP due to SAH showed two peak appearances: the first was within 24 hours (n = 3), and the second was around 10 days after onset (n = 3). The cause of TCP in its late peak appearance was presumed to be the consumption of platelets due to microembolism induced by vasospasm and/or hemodilution therapy. Among patients with ICH, five cases were in the acute stage, three in the subacute stage and two in the chronic stage. TCP due to ICH was more likely to develop in the acute stage. Fifty percent (4/8) of the patients with ICH had TCP on admission. This data suggested that TCP was possibly a cause or an inducer for ICH.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1896117 TI - [Pulmonary embolism complicated with stroke: analysis of 5 cases]. AB - Though pulmonary embolism (PE) has been thought to be rare, the incidence seems to be increasing recently. During the past 10 years the authors have encountered 5 cases of PE among stroke patients. There were 2 males and 3 females, aged 51 to 71 years (mean age; 63 years). The mean time between admission and onset of PE was 23 days. As to the primary disease to be treated, 5 patients had subarachnoid hemorrhage and one had intracerebral hemorrhage. Generally, PE tends to be overlooked or misdiagnosed because of the fact that stroke patients are often in a state of unconsciousness. In our series, only one patient complained of dyspnea and the other 4 patients due to unexplained sudden tachycardia, tachypnea and hypoxemia were suspected to have PE. Deep venous thrombosis known as the risk factor leading to PE was presented in 3 patients. Especially in one patient, femoral venous catheterization was considered as a risk factor possibly leading to deep venous thrombosis. Regarding the diagnosis of PE, the roles of electrocardiogram and of chest x-ray film were small. In 3 patients, the elevation of the diaphragm was the only abnormal finding on chest X-ray. On the other hand, the lung scintigram with 99mTc-MAA was a useful method for definitive diagnosis of PE. In 3 patients, filling defects were demonstrated on the lung perfusion scintigrams. Consequently, we emphasize that PE must be kept in mind when tachycardia, tachypnea and hypoxemia appear suddenly. Prompt diagnosis and treatment are required.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1896119 TI - [A case report; ganglion cyst of a cervical facet joint]. AB - Ganglion or synovial cyst typically occurs in peripheral joints and tendon sheaths such as elbow joint or wrist joint, but rarely in the spinal facet joint. From reported cases the most common site involved seems to be the lumbar facet joint. Only three cases of cervical ganglion or synovial cyst have so far been found in the literature. A case of cervical ganglion cyst was reported. The patient was a 2-year-old boy who was found to have a tumor in the midline of the nape. He had no history of trauma. Neurological and physical examination revealed no abnormalities. On CT scan a round low dense lesion with clear margin was found in the nape. Enhanced CT scan showed ring-like enhancement. Magnetic resonance (MR) imaging showed a well defined lesion of high intensity on T1- and T2 weighted images. At operation, the lesion was found to form a cyst containing old hematoma, and the cyst wall seemed to be fixed to the cervical spinal facet joint. The tumor was histologically diagnosed as ganglion cyst. PMID- 1896118 TI - [A case of pituitary adenoma and hyperplasia with primary hypothyroidism]. AB - A 23 year-old woman was admitted to our hospital, complaining of sterility and obesity. Her serum TSH and Prolactin were abnormally high, and her serum T3, T4 were low. Contrast-enhanced computerized tomographic (CT) scan revealed a round mass in the sella and suprasellar region. A transsphenoidal operation was then performed. The intrasellar mass was composed of a soft liquid-like part and a solid part. Only the soft liquid-like part of the mass was removed. Histological examination showed the typical appearance of chromophobe adenoma, Reticulin stain of the specimen revealed no reticular network. The remnant of the mass was considered to be hyperplasia because the size of the mass decreased on serial CT scan after thyroid hormonal replacement. Sometimes it may be difficult to distinguish between hyperplasia and adenoma. The application of reticulin stains is considered to be useful for differentiation between hyperplasia and adenoma. PMID- 1896120 TI - [Combination chemotherapy with cisplatin and etoposide for cerebellar metastasis from ovarian adenocarcinoma]. AB - A 54-year-old woman with cerebellar metastasis from ovarian adenocarcinoma was reported. Two years before admission, she underwent 7 courses of CAP therapy (cisplatin, adriamycin, cyclophosphamide) for ovarian cancer. On admission, no extracranial tumor was noticed. After the removal of a cerebellar tumor, she was treated by combination chemotherapy with cisplatin and etoposide. Her serum level of CA-125, which was still high after surgery, decreased to the normal level following chemotherapy. Chemotherapy was repeated six times, and no recurrence was noticed 1 year after surgery. Combination chemotherapy with cisplatin and etoposide was considered effective in the treatment of intracranial metastasis from ovarian cancer. PMID- 1896122 TI - [A case of meningioangiomatosis in an infant]. AB - We report here a rare case of meningioangiomatosis in an infant, not associated with von Recklinghausen's disease. A 14-month-old female was admitted because of seizures. Neurological findings on admission were normal. Computed tomography showed a slightly high density mass with marked contrast enhancement in the left temporoparietal lobe. Magnetic resonance image (MRI) revealed a slightly hypointensive lesion surrounded by an isointensive band on T1-weighted image, and a hyperintensive lesion surrounded by a slightly hypointensive band on T2 weighted image. Brain edema was shown to a certain extent around the lesion on MRI. Left carotid angiography demonstrated a slightly upward shift of the left middle cerebral artery, but no abnormal vascularity was shown. A temporoparietal craniotomy was performed. A yellowish red, elastic soft tumor was observed in the left temporal lobe. The tumor resembled hyperemic hypertrophic gyri and was well demarcated. Total removal of the tumor was performed. Pathological diagnosis was meningioangiomatosis. The patient is still doing well 3 years and 5 months after the operation. There was no evidence of recurrence on computed tomography at the 3-year follow up. She didn't have any stigmata, such as cafe au lait spots or neurofibromas suggesting von Recklinghausen's disease. PMID- 1896121 TI - [A case of angiomatous meningioma near the geniculate ganglion]. AB - A 57-year-old male was admitted with pulsatile tinnitus and hearing disturbance of the right ear and right peripheral facial palsy. Otological examination revealed a pulsatile red mass in his right ear and right conductive hearing disturbance. CT and MRI showed the mass lesion at his right middle fossa near the geniculate ganglion. Right external carotid angiogram disclosed a tumor stain fed by the middle meningeal artery. The tumor was removed via a combination of subtemporal and transmastoidal approaches. Histologically, this tumor was diagnosed as angiomatous meningioma partly with meningotheliomatous meningioma. Meningioma in this region is very rare. We discussed its clinical and radiological characteristics in comparison with chemodectoma and facial neurinoma at the geniculate ganglion. PMID- 1896123 TI - [Traumatic carotid-cavernous fistula presenting subarachnoid hemorrhage 5 years after head injury; case report]. AB - A case of traumatic carotid-cavernous fistula (CCF) which presented subarachnoid hemorrhage long after the injury is reported. A 24-year-old male was admitted to the National Yokohama Hospital with complaints of severe headache and nausea. CT scan and cerebral angiography showed subarachnoid hemorrhage due to ruptured CCF. His right visual acuity has disappeared after a traffic accident 5 years before, and he had hit his forehead again 3 years previously. He experienced severe headache twice for 2 weeks after his admission. He was transferred to Kanagawa Rehabilitation Center to be treated with intravascular surgery. Plain CT showed high density areas in the basal cisterns. CT after contrast infusion disclosed a small enlarged high density area in the right cavernous sinus, and showed an enhanced mass lesion in contact with the right ventrolateral side of the midpons. The right internal carotid angiogram showed high flow CCF, fed only by the internal carotid artery. It drained mainly into the basilar plexus, partially into the basal vein of Rosenthal and the inferior petrosal sinus. The CCF was found at the C4 portion of the right internal carotid artery. CT and the angiogram revealed a part of the CCF developing into a varix in the ventral side of the prepontine cistern. It ruptured and the patient developed subarachnoid hemorrhage 5 years after the head injury. The CCF was intravascularly embolized by a detachable balloon. Early treatment for CCF is necessary to prevent the occurrence of subarachnoid hemorrhage if a part of the CCF develops into a varix. PMID- 1896124 TI - [A ruptured aneurysm in the hypoplastic proximal anterior cerebral artery (A1 portion); case report]. AB - A case of ruptured aneurysm in the hypoplastic proximal anterior cerebral artery (A1 portion) is reported. This 25-years old man complained of the sudden onset of severe headache and vomiting on January 11, 1989. He was referred to our hospital on the same day, and CT scan revealed subarachnoid hemorrhage. Cerebral angiography on the next day revealed an aneurysm in the hypoplastic A1 portion of the right anterior cerebral artery, and no branch was present at the site of the aneurysmal neck. He was operated on using the right pterional approach. The A1 portion was trapped and the aneurysm was removed successfully. The histology of the aneurysm was that of the usual type of the saccular aneurysm. The post operative course was uneventful. He was discharged with no neurological deficit two months after the operation. As far as we know, there has been no report on a ruptured aneurysm in the hypoplastic A1 portion. We also reviewed the 55 aneurysms in the A1 portion that have been reported in the literature. PMID- 1896125 TI - [A case of intracerebellar hemorrhage in infancy]. AB - Nontraumatic intracerebellar hemorrhage is rare during childhood. We report such a case due to rupture of arteriovenous malformation, in which surgery was able to bring about satisfactory recovery from deep coma without spontaneous respiration. This case shows that operative treatment should not be abandoned even though neurological deficits are very serious. This 6-year-old boy suddenly complained of headache while playing in a nursery and became restless. Because of deterioration of consciousness level followed by loss of respiration, he was transferred from a local physician to our clinic 4 hours after the onset. Computerized tomography scan disclosed a hematoma in the cerebellar hemisphere. Emergency suboccipital craniectomy was carried out 1 hour later. Immediately after operation, respiration was restored. Vertebral arteriography was performed 1 month after the operation, when the patient had recovered but could barely communicate with his family. The study revealed a small arteriovenous malformation supplied by the anterior inferior cerebellar artery. The malformation was removed 3 months after admission. The postoperative course was uneventful and the patient attended a primary school without neurological deficits except for slight ataxia 6 months after the onset. PMID- 1896126 TI - [One pedigree of "moyamoya" disease]. AB - One familial case of "moyamoya" disease affecting three patients is reported. The patient in Case 1 was a 28-year-old female. She had suffered from motor weakness of the right limbs in her infantile period. She visited our hospital because of sudden headache and left motor weakness associated with nausea and vomiting. On admission, CT scan revealed cerebral hemorrhage in the right caudate nucleus with intraventricular clots and infarction in the left parietal lobe. Angiography showed stenosis of the left ICA terminal portion and occlusion of the right side, with moyamoya vessels in the basal area. The patient in Case 2 was a 54-year-old female, who was the mother of Case 1. After an operation for acute upper intestinal bleeding, she suffered from cerebral infarction. CT scan revealed large low density areas in the territory of the bilateral MCA. Angiography showed stenosis of the bilateral ICA terminal portions, occlusion of the right MCA, stenosis of the left MCA, and moyamoya vessels in the basal area. The patient in Case 3 was a 40-year-old female, who was a younger sister of Case 2. She had a convulsive attack in her infantile period. She visited our hospital because of gradually worsening headache. CT scan revealed multiple infarctions in the left paraventricle, the right parieto-occipital and occipital lobe. Angiography showed occlusion of the bilateral ICA terminals with moyamoya vessels in the basal and the ethmoidal areas. The patient in Case 2 died immediately. Surgery for reconstruction of hemodynamics was performed in Case 1 and 3.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1896127 TI - [Pseudoaneurysm of the extracranial vertebral artery; a case report]. AB - Traumatic injury of the vertebral artery is rare and only a few reports have been presented. We treated a case of iatrogenic pseudoaneurysm of the extracranial vertebral artery. A 65-year-old man complained of headache and had a pulsating mass in the soft tissue of the neck which had continued for one month after evacuation of hypertensive cerebellar hemorrhage. The left VAG revealed a large pseudoaneurysm at the third portion of the vertebral artery and the right retrograde VAG revealed agenesis of the vertebral artery. To select the proper treatment was a dilemma. This case was treated by embolization using an occluding spring embolus with direct transcutaneous puncture of pseudoaneurysm. Following this treatment, the mass and associated symptoms resolved without neurological deficit. PMID- 1896128 TI - [Extremely low birth-weight infant with hydrocephalus; management of hydrocephalus using a miniature Ommaya's reservoir]. AB - Use of the miniature Ommaya's reservoir in the treatment of extremely low birth infant (under 1,000 mg) with hydrocephalus was studied in a series of five patients. The reservoir has a small-caliber with a 3 cm ventricular catheter. For these infants, this miniature Ommaya's reservoir is extremely useful for protection of the cortical mantle until a definitive procedure can be carried out after increase of body weight. The clinical course in five cases are summarized. PMID- 1896129 TI - Current bibliographies of neuropeptides prepared by the University of Sheffield Biomedical Information Service. PMID- 1896130 TI - Quantitative evaluation of octadecaneuropeptide-like immunoreactivity in hippocampus, cortex and cerebellum of long-term isolated male Wistar rats. AB - Quantitative evaluation of octadecaneuropeptide-like immunoreactivity (ODN-Li) was carried out in hippocampus, cortex and cerebellum of group-reared or three month isolated male Wistar rats, whether muricidal or not. ODN-Li was lower in cortex and cerebellum of isolated animals, (mainly in muricidal) than of group reared ones. A similar trend was apparent in the hippocampus. No significant differences were observed between muricidal and non-muricidal animals. The results are discussed in terms of the involvement of the endogenous ligands of the GABA-benzodiazepine receptor complex in the integrations related to mood and behaviour. PMID- 1896131 TI - Interaction of corticotropin-releasing factor (CRF) and alpha-helical CRF on rat neurointermediate lobes: in vitro studies. AB - Neurointermediate lobes (NILS) of the pituitary glands of adult male Sprague Dawley rats were incubated in media in the presence of corticotropin-releasing factor (CRF), a stimulator of proopiomelanocortin (POMC) peptide release. Alpha helical CRF, a peptide known to inhibit CRF induced POMC peptide release from the anterior pituitary, was incubated with NILS for a period of 90 min, to study its potential ability to modulate peptide release from the intermediate lobe. The alpha-helical peptide reduced beta-endorphin release from NILS, as measured by radioimmunoassay (RIA), when added for the entire incubation, or when added 30 min after start of the incubation period, with CRF present. Alpha-helical CRF alone reduced beta-endorphin release, as compared to control or CRF-treated lobes. Ultrastructural examination of intermediate lobes fixed at the end of incubations revealed a reduction in the numbers of Golgi-associated dense granules, an indicator of new peptide synthesis, in intermediate lobe tissue treated with alpha-helical CRF alone, both peptides together, or with CRF followed by alpha-helical peptide. The in vitro studies demonstrate the effectiveness of the antagonist peptide on intermediate lobe peptide secretion, thereby extending its effects to both POMC-secreting areas of the pituitary gland. PMID- 1896132 TI - Properties of associative long-lasting potentiation induced by cellular conditioning in the motor cortex of conscious cats. AB - Mechanisms of long-lasting potentiation of synaptic responses induced in the thalamocortical and recurrent collateral pathways of the pyramidal tract were studied in intracellular recordings from the motor cortex of unanesthetized, chronically implanted cats. The observations provide the first description of long-lasting potentiation in the unanesthetized neocortex in vivo. Monosynaptic excitatory postsynaptic potentials of 2-5 mV in amplitude were evoked as test responses by stimulation of the pyramidal tract and thalamic ventrolateral nucleus at 0.1-0.5 Hz frequency. Pressure microinjections of drugs and ions were also performed during intracellular recordings. In the first series of experiments, test synaptic responses were paired with intracellular current injection-induced action potentials at an interstimulus interval set between 0 200 ms and 0.1-0.5 Hz frequency. Pairings (30-100 x) induced long-lasting potentiation of the test responses in 58% of cells. The increased synaptic responses typically initiated action potentials and their potentiation usually lasted over the period of recordings. Increases in amplitude of synaptic responses were not correlated with statistically significant changes in electrical membrane properties (resting potential, input resistance, time constant, spike threshold) or parameters of action potentials and their afterpotentials. The failure to induce increases in synaptic efficacy by unpaired stimuli (pseudoconditioning) demonstrated the associative property of the long lasting potentiation. In a second series of experiments, differential cell conditioning was employed. This paradigm induced long-lasting potentiation of the explicitly paired synaptic response without noticeable modification of unpaired or pseudorandomly paired synaptic responses tested conjointly in the same neuron. These observations demonstrated the input-specificity of long-lasting potentiation. In a third series of experiments, subthreshold depolarizing current pulses were summated with synaptic responses to induce firing in the recorded neuron during pairing. Long-lasting potentiation occurred in 55% of the summated synaptic inputs. Pseudoconditioning did not induce synaptic potentiation in these cells. In a fourth series of experiments, conditioning was employed in neurons in which firing activity was suppressed by an intracellularly injected lidocaine derivative. Long-lasting potentiation was induced in 50% of the attempts when synaptic responses were paired with current-induced depolarizations greater than 30 mV. These results suggest that postsynaptic induction of long-lasting synaptic potentiation can be successful in the absence of postsynaptic sodium spikes in neurons of the motor cortex in vivo. In a fifth series of experiments, homosynaptic high-frequency tetanization (80-200 Hz for 5-15 s) was applied to the thalamocortical and recurrent pyramidal afferents.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1896133 TI - Increase of striatal methionin enkephalin content following lesion of the nigrostriatal dopaminergic pathway in adult rats and reversal following the implantation of embryonic dopaminergic neurons: a quantitative immunohistochemical analysis. AB - The aim of the present study was to test whether intrastriatal implants of embryonic dopaminergic neurons are able to normalize the lesion-induced dysfunction of striatal enkephalinergic neurons, one of the major output systems of the striatum. The ascending dopaminergic pathway of adult rats was unilaterally lesioned. Three weeks later a cell suspension obtained from the mesencephali of ED14 rat embryos was implanted into the denervated striatum and striatal methionin enkephalin immunostaining was quantified six months later by the use of an image analyser. Methionin enkephalin immunostaining was unevenly distributed in the striatum of control animals. Besides the classical patch/matrix pattern, a mediolateral gradient was also present and, moreover, immunostaining decreased towards caudal levels. Seven months after the lesion of the nigrostriatal dopaminergic pathway, methionin enkephalin immunostaining was found to be increased in the denervated striatum by about 50%. However, relative increases were more sustained in the areas where basal methionin enkephalin immunostaining were lowest, i.e. the lateral striatum and posterior striatal areas. This resulted in an attenuation of the global gradients seen in the normal striatum. Increased immunostaining was also found in the ipsilateral globus pallidus. The implantation, into the denervated striatum, of embryonic dopaminergic neurons led to a reversal of the lesion-induced increase of striatal and pallidal methionin enkephalin immunostaining six months later. Moreover, this reversal resulted in an overshoot, as the level of immunostaining in the graft bearing striatum was found to be lower than the levels found in the normal striatum. It is concluded that grafts of embryonic dopaminergic neurons can normalize the function of one of the major output systems of the striatum and, through it, influence more distant targets of this structure. This suggests a physiological basis for the behavioral effects observed previously with such grafts. PMID- 1896134 TI - Serotonin-immunoreactive varicosities in the cell body region and neural sheath of the snail, Helix pomatia, ganglia: an electron microscopic immunocytochemical study. AB - The distribution and connections of serotonin-immunoreactive fibers in the cell body region and neural sheath of the central ganglia of the snail, Helix pomatia, have been examined. The cell body region of the ganglia is supplied by an extremely dense network of varicose serotonin-immunoreactive fibers which surround neuronal perikarya in the ganglia. Immunoreactive processes also run to the neural sheath of both the ganglia and the peripheral nerve roots, forming a dense network. Electron microscopy revealed five different connections of serotonin-immunoreactive varicosities, according to their target: (i) non specialized contacts with neuronal perikarya; (ii) non-specialized contacts with axon processes on the surface of the peripheral nerve roots; (iii) non specialized neuromuscular connections with smooth muscle fibers in the neural sheath; (iv) varicosities engulfed by glial processes in both the cell body region and neural sheath; (v) varicosities embedded in the connective tissue elements of the sheath either partly or completely free of glial processes. In all cases of appositions no membrane specializations could be observed on either site of the contacts. These observations provide morphological evidence for non synaptic regulatory actions of serotonin-containing neurons in Helix central nervous system: (i) modulation of the activity of neuronal perikarya; (ii) involvement in neuromuscular regulation; (iii) neurohormonal modulation of peripheral processes by release through the neural sheath. PMID- 1896135 TI - The lacunar glial zone at the periphery of Aplysia giant neuron: volume of extracellular space and total calcium content of gliagrana. AB - The relative volume of perineuronal extracellular space, the number of gliagrana and their total calcium content have been measured in Aplysia punctata and A. californica, at the periphery of giant neurons R2 and LP1. After chemical fixation, the extracellular space amounts to 26% of the periganglionic glial zone, but this increases to 36% after quick freezing and freeze-substitution. The glial cytoplasm contains gliagrana, membrane-bound granules approximately 0.3 micron in diameter. The number of gliagrana per micron 2 of section, defined as "abundance", was counted in electron micrographs of chemically fixed tissues. The abundance of gliagrana appears to be directly proportional to the volume of the extracellular space when the values are averaged per individual Aplysia. The total calcium concentration of the gliagrana is measured by X-ray microanalysis on sections of ganglia processed by rapid freezing and freeze-substitution in the presence of oxalic acid: it was found to be very high. An individual granule may contain 100 mM Ca in A. californica and 50 mM in A. punctata but in both species the calcium concentration varies along a wide range as if there were different functional states of the granules with respect to this concentration. The total calcium stored in the specific granules of the glial zone was estimated. It was calculated that should the glial calcium store be entirely diluted in the extracellular space of the glial zone, it would raise the calcium concentration of this space by approximately 1 mM (0.1-2.7 mM). These findings are discussed with regard to the hypothesis of glial cells regulating the perineuronal calcium concentration. PMID- 1896137 TI - Alternatives in restorative dentistry. PMID- 1896136 TI - A proposed relationship between circumference and conduction velocity of unmyelinated axons from normal and regenerated cat hindlimb cutaneous nerves. AB - Data on the conduction velocities and circumferences of unmyelinated axons in cat hindlimb nerves obtained in two laboratories, each working independently of the other, have been brought together and compared. Results were obtained from normal, regenerated and deafferented nerves. Matching the conduction velocity and circumference distributions against one another suggested that conduction velocity (theta), in m/s, is linearly related to circumference (s), in microns, according to the equation theta = 0.24s. If this relationship is correct, it applies equally well to both sympathetic postganglionic and unmyelinated afferent axons. PMID- 1896138 TI - Why amalgam? PMID- 1896139 TI - Direct composite resin restorations in posterior teeth. PMID- 1896140 TI - The composite resin inlay as an alternative to amalgam. PMID- 1896142 TI - Choices or horses for courses. PMID- 1896141 TI - Alternatives to amalgam--the role of bonded porcelain. PMID- 1896143 TI - Variations in root canal anatomy. AB - The tenets of root-canal treatment are the preparation, cleaning, and sealing of the root canals. An understanding of the variations in root-canal anatomy is necessary by those carrying out treatment. Recognition of a variation when it occurs is the first and most frequent step in completing successful treatment for these teeth. PMID- 1896144 TI - Lingual orthodontic appliances: invisible braces. AB - Lingual orthodontics is a relatively new method of delivering orthodontic treatment. These appliances may be used on any patient, but they have a special application for that small group of adult patients who need orthodontic treatment but refuse to accept the appearance of conventional appliances. The technique is difficult to manage and should be used only by experienced orthodontists. Although the patients may experience difficulties, these are usually adequately compensated for by the improved aesthetics. PMID- 1896145 TI - Fluoride and hip fracture. PMID- 1896146 TI - Report on AIDS. PMID- 1896147 TI - Get it in writing. PMID- 1896148 TI - DSSNY joins in ADA third-party problem resolution pilot. PMID- 1896150 TI - Clinical realities of endosseous blade vent implants. PMID- 1896149 TI - Implantology in dentistry. A brief historical perspective. PMID- 1896151 TI - The tridimensional biblade implant reentry system. PMID- 1896153 TI - Implant dentistry, the specialty. PMID- 1896152 TI - Implant treatment of the severely atrophic mandible. PMID- 1896154 TI - Series details AIDS prevention in dental offices. PMID- 1896155 TI - The era of implants. PMID- 1896157 TI - OH sidelined again? PMID- 1896158 TI - Divers and AIDS. PMID- 1896156 TI - The doctor as ethicist. PMID- 1896159 TI - The portable mind machine. PMID- 1896160 TI - Office ergonomics: the wimp factor? PMID- 1896161 TI - Sitting and the VDU directive. PMID- 1896162 TI - Pre-employment medicals and informed consent. PMID- 1896163 TI - AIDS and health care workers. PMID- 1896164 TI - Sickness dismissals. PMID- 1896165 TI - What constitutes a complication? A dilemma of real significance. PMID- 1896166 TI - Modified levator aponeurosis recession for upper eyelid retraction in Graves' disease. AB - Recession of the levator aponeurosis has proved to be an excellent operation to correct upper eyelid retraction in Graves' disease. Harvey and Anderson's original description included recession of the levator aponeurosis along its entire width and complete extirpation of Muller's muscle. In a modification of the technique, we recess only the lateral two thirds of the levator/Muller's complex. Also, rather than excising Muller's muscle, we simply recess it en bloc with the levator aponeurosis. The lateral horn of the levator is cut, as previously advocated, to relieve the marked temporal elevation of the eyelid characteristic of Graves' lid retraction. This modified procedure provides good upper lid lengthening, with less surgical manipulation, less bleeding, and avoids medial over-corrections. Of 22 upper lids (12 patients) treated with this procedure, 19 (86.3%) were considered "good" after the operation. PMID- 1896167 TI - Surgical treatment of eyelid retraction associated with thyroid eye disease. AB - Fifteen patients (22 eyelids) were treated for upper eyelid retraction related to thyroid eye disease by recessing the levator aponeurosis and Muller's muscle through a lid crease incision. Neither spacers nor traction sutures were used, and the recessed muscles were not sutured to any of the surrounding tissues. The patients were not sedated and thus were able to sit up during the procedure; final lid heights also were determined with the patients in the sitting position. There were no overcorrections or undercorrections during follow up of at least 3 months. PMID- 1896168 TI - The Glaucoma Laser Trial: 4. Contralateral effects of timolol on the intraocular pressure of eyes treated with ALT. GLT Research Group. AB - Several reports have documented a contralateral intraocular pressure (IOP) lowering effect after unilateral instillation of timolol. Data derived from the Glaucoma Laser Trial (GLT), a randomized trial of the efficacy and safety of argon laser trabeculoplasty (ALT) as compared with the efficacy and safety of topical medications as initial therapy for primary open-angle glaucoma (POAG), demonstrated an estimated mean pressure reduction of 0.5 mm Hg in the contralateral eye that had received ALT. This contralateral effect is smaller than that observed in other studies of POAG patients. Lower initial IOP, longer duration of treatment with timolol, and/or improved outflow facility modulation in the ALT-treated eyes may be responsible for the smaller contralateral effect of timolol observed in the GLT patients. PMID- 1896169 TI - Epithelial downgrowth following the removal of iris inclusion cysts. AB - We present three patients in whom epithelial downgrowth occurred following the excision of iris inclusion cysts. The sheet-like downgrowth was aggressively treated and successfully eradicated in two of the three patients. Early identification and prompt therapy are essential. PMID- 1896170 TI - The effects of glaucoma medications on Tenon's capsule and conjunctiva in the rabbit. AB - Glaucoma filtering surgery fails most frequently due to fibrosis at the episcleral-conjunctival/Tenon's capsule interface. Sherwood et al have suggested that chronic topical antiglaucoma medications increase conjunctival inflammatory cells, which could increase the likelihood of fibrosis and subsequent bleb failure. In a pilot study in a rabbit model, we placed timolol, pilocarpine, and epinephrine, or a combination of all three, in one eye of 24 animals twice daily for 7 months. The fellow eye received distilled water. Microscopic examination revealed no statistically significant change in the number of acute or chronic inflammatory cells, fibroblasts, or goblet cells in the treated as compared with the control eyes. A longer duration of drug administration, or drug administration followed by surgical intervention, may be required to produce an effect on the conjunctiva and Tenon's capsule, if such an effect exists. PMID- 1896171 TI - Intraepithelial sebaceous epithelioma of lids, conjunctiva, and cornea treated with minimal orbital exenteration. AB - "Minimal" orbital exenteration, obtained by excision of a lid tumor (that had recurred after local incision), removal of the conjunctival sac, enucleation, and tenonectomy were used to treat intraepithelial sebaceous epithelioma with pagetoid spread to conjunctiva and cornea in an 80-year-old man. PMID- 1896172 TI - A new contact neodymium:YAG laser for cyclophotocoagulation. AB - A newly developed compact (40 kg), self-contained contact Neodymium:YAG laser produces high-peak, high-energy (800 mJ/pulse), short (1.0 millisecond) pulses with 1 to 3 pulses/exposure. Energy is delivered via a 320-microns cleaved quartz fiber optic probe. Cyclophotocoagulation was performed in five eyes of three medium-sized Dutch-pigmented rabbits. The eyes received exposures of 1 to 3 pulses/exposure. Energy delivered ranged from 100 to 800 mJ/pulse. Histopathology revealed ciliary body disruption and hemorrhage with no damage to overlying sclera. When used for transscleral cyclodiathermy in the rabbit, the laser created significant ciliary body disruption with minimal scleral injury. PMID- 1896173 TI - The effect of dexamethasone on the inhibition of pseudophakic bacterial endophthalmitis. AB - We investigated the effect of dexamethasone on gentamicin prophylaxis of pseudophakic bacterial endophthalmitis in a rabbit model. In 20 eyes treated with gentamicin and either dexamethasone or dexamethasone vehicle, there were no cases of either clinical or culture-positive endophthalmitis. PMID- 1896174 TI - Anterior capsule adherence to iris leading to pseudophakic pupillary block. AB - We present a rare case of anterior capsule adherence to the iris following extracapsular cataract extraction with posterior chamber intraocular lens implantation and leading to pseudophakic pupillary block. There were no synechiae at the pupillary margins associated with the capsule/iris adherence, but aqueous was entrapped behind the iris and intraocular pressure rose. Laser iridotomy was temporarily beneficial, but it had to be repeated several times. PMID- 1896175 TI - Techniques for application of tissue adhesive for corneal perforations. AB - We describe a modified technique of using cyanoacrylate adhesive to seal corneal perforations. Easily performed at the slit lamp, its advantages over previously described methods include a smooth, contoured collagen surface overlying the adhesive, which is easily wet by the tear film. Even greater comfort and protection are provided by the addition of a hydrophilic bandage lens or collagen shield. PMID- 1896176 TI - Repair of inferior iridodialysis using a partial-thickness scleral flap. AB - We present a technique of inferior iridodialysis repair using a partial-thickness scleral flap, which, in turn, employs a modification of the technique currently used to suture posterior chamber intraocular lenses under scleral flaps. PMID- 1896177 TI - A disposable 8-mm "corneal cap" to reduce surgical light exposure. AB - I have devised an easily-fashioned disposable "corneal cap" that reduces light exposure to the retina from the operating microscope. The 8-mm plastic cap is the cut end of the test chamber included in all packages of disposable handpieces and tubing for automated irrigation and aspiration instruments. PMID- 1896178 TI - "Equator ring" for maintenance of the completely circular contour of the capsular bag equator after cataract removal. AB - We designed an "equator ring," a flexible silicone rod with a groove on its inner surface, to maintain the circular contour of the capsular bag equator after cataract removal. After cataract extraction, the ring is inserted in the bag through a 5.0-mm circular capsulorhexis or 4.5-mm linear "dumbbell" opening. Then a conventional posterior chamber intraocular lens (PC-IOL) is inserted, with the IOL loops in the groove. The ring not only allows complete maintenance of the circular contour of the capsular bag equator for most conventional PC-IOLs, but also may prevent invasion of metamorphosed lens epithelial cells into the posterior capsule. PMID- 1896179 TI - Reattachment of the detached ciliary body with suturing for treatment of contusional ocular hypotension. AB - Ocular hypotension resulting from a detached ciliary body after ocular contusion usually is best treated surgically. We report a simple, safe, and relatively effective procedure used to suture the ciliary body onto the inner surface of the sclera in eight such cases. Intraocular pressure (IOP) rose from unmeasurable levels to 10 to 12 mm Hg in five of these cases. Although in the three other cases IOP did not increase immediately after the operation, in one case it rose to 10 to 12 mm Hg 1 month postoperatively, and in the other two cases it rose to a normal level after additional laser therapy. PMID- 1896180 TI - [Organization of the osseous nasal septum and its homologues. IV-C. Alar bone composed of sub-nasal and septal bones. Nasal septum and axial palate complex (represented by artiodactyla and leporidae)]. AB - The aim of this investigation was the study of the development changes of the osseous nasal septum and para-sphenoid systems in adult pigs, domestic cattle and the comparison with the control skull-group of 10 deer and 15 hares. The methodology was described elsewhere. In paired-hoof mammals was found that the alar bone is biomechanically composed system. It represents four segments: three of septum bone and one as subnasal bone. In examined mammals the degree of integration of sphenoid septum and alar bone ones was various. In fishes, amphibians, birds and paired-hoof mammals there are the axially palate system too. The para-sphenoid mechanically integrated itself with the hard palate. PMID- 1896181 TI - [Influence of alcohol on morphological changes of the laryngeal and pharyngeal mucosa]. AB - The long term intake of the ethyl alcohol by rats caused the morphologic changes of plano-epithelial and subepithelial layer of the larynx mucosa. The most expressed lesions were the disconnection of the epithelial structures and its taking into pieces. The changes were accentuated by longer alcohol intake, especially in morphology, size and color. PMID- 1896182 TI - [Chromosomal polymorphism in patients with otospongiosis]. AB - Cytogenetic examinations were performed on 18 patients with surgically verified otosclerosis. In comparison with 15 healthy patients satellites in the somatic chromosomes of D and G groups were found to occur significantly more frequently (p less than 0.005). Moreover, among the patients a case of 45,X karyotype with clinically incomplete Turner syndrome has been disclosed. The results obtained seem to support genetic hypothesis of otospongiosis pathogenesis. PMID- 1896183 TI - [Spontaneous neoplastic transformation of laryngeal papilloma in adults]. AB - The process of spontaneous malignancy of laryngeal papilloma in 80 adults was analysed: 36 with juvenile papilloma and 44 with hyperkeratotic papilloma. In all of the cases, surgical removed material was serially examined histopathological to observe very early process of cancerogenesis of a different degree of cellular dysplasia. In clinical evidence, cases with juvenile papilloma had leukoplakia on the surface of the papillomas. Only in two cases with numerous recurrences were leukoplakia and dysplasia of cells permanent and only one showed a fully developed carcinoma. Hyperkeratotic papillomas are undoubtedly a pre-carcinoma condition, because 70.5% of cases revealed evidence of becoming malignant idiopathically. Malignancy had its beginning in deep base layers. There were two possibilities of developing papilloma hyperkeratotic: carcinoma spinocellular or carcinoma verrucosum. PMID- 1896184 TI - [Concentration of total and protein-bound hydroxyproline in serum and urine in patients with laryngeal neoplasms]. AB - The concentration of total and protein-bound hydroxyproline in the serum and total hydroxyproline in the urine was measured in the group of 52 patients with larynx carcinoma by means of Prockop's and Udenfriend's colorimetric method modified by Tomaszewski. The mean level of total and protein-bound serum hydroxyproline in the group of clinical patients was statistically significantly raised when compared with control group. The mean level of total hydroxyproline in the urine of patients with larynx carcinoma was statistically insignificantly raised when compared with control group. The degree of clinical or organic progress of larynx carcinoma was not found to influence essentially the level of hydroxyproline in the serum of the examined patients. It was shown however, that statistically essential increase in the total hydroxyproline level in the urine depends on the degree of organic progress of larynx carcinoma. PMID- 1896185 TI - [Olfactory neurinoma in material from the Cracow Oncologic Center during the years 1970-1987]. AB - 4 patients with the olfactory neurinomas treated in Cracow Oncologic Center were described. The up to date opinions of the treating methods were also presented, especially the coincidence of surgery and radiotherapy. PMID- 1896186 TI - [Nasal cytology in patients with non-seasonal atopic rhinitis]. AB - The results of the cytological evaluation of the nasal smears taken from the patients with non-seasonal atopic rhinitis were presented. In 95% of smears a very abundant cytological material of the columnar epithelium cells was found. The smears taken by cyto-brushing (Medscand) showed the presence of the cytological material from the whole nasal mucosa, while those taken by the loop contained the cells from the small area of the mucosa. PMID- 1896187 TI - [Evaluation of collagenous protein levels in inflamed middle ear mucosa]. AB - The collagenous protein level in the inflammatory status of middle ear mucosa taken during the surgery in 16 patients were analysed. The more accentuated changes were in longer duration of disease. The collagenous protein level play probably an important role in the healing processes after tympanoplasty. PMID- 1896188 TI - [Laryngeal carcinoma in women]. AB - In the total number of 1032 patients with laryngeal carcinoma treated surgically in the period 1962-1988 were 26 women (2.5%). In 17 women total laryngectomy was carried out. Partial laryngectomy was done in 9 women. Long term results were discussed. PMID- 1896189 TI - [Auditory brainstem responses in full-term infants and pre-term neonates]. AB - Auditory Brainstem Responses (ABR) and behavioural threshold were studied in 52 infants born between 28-41 weeks of gestational age (GA), which have been between 33-42 weeks of postconceptional age (PCA) (Gestational age + postnatal age). Peak latencies of wave V and interpeak latency I-V were measured as a function of maturational changes and stimulus intensities. Behavioural audiometric threshold to pure tone were determined through behavioural observation of auditory palpebral reflex. In the group of full-term infants threshold responses for clicks lay between 32.5 to 35.1 dB. In the group of pre-term neonates the threshold lay between 37.6 do 40 dB. Behavioural audiometry disclosed that full term infants responded to pure tone stimuli with mean threshold of 86 dB, while the pre-term infants would respond to pure stimuli at 91 dB. The latency of wave V responses decreases progressively from a mean of 7.84 ms at 33-35 weeks of PCA, to 6.57 ms at 40-41 weeks of PCA. The ABR shows a remarkable variability in wave V latency with relatively stable interpeak latency I-V with decreases stimulus intensities. PMID- 1896190 TI - [Tonal audiometry in hearing evaluation with a microcomputer system]. AB - The own experiences with the computer microsystem for hearing evaluation "Audiocomp" were presented. The air and bone conduction thresholds as well as the others suprathreshold testing were performed by computer. The reproducibility of results were better than in standard audiometry. The influence of the examined person is lowered making the testing more objective. PMID- 1896191 TI - [A contribution to diagnosing receptive-expressive dysphasia]. AB - Diagnosis of disturbances of speech and the language of the receptive-expressive type of dysphasia was described in 8-year-old child. These disturbances were found to be the problems in learning. Complex clinical evaluation of such cases was stressed as very important. PMID- 1896192 TI - [Detection of precancerous and cancerous states of the larynx]. PMID- 1896193 TI - The behaviour of health care providers in managing diarrheal disease in Palembang City, south Sumatera, Indonesia. AB - A study on knowledge, attitude and practice of health care providers in Palembang had been conducted at the end of 1989 and beginning of 1990. Four approaches were carried out: (1) by recording the help obtained by cases who consulted researchers for further help for the same diarrheal diseases (DD) episode, (2) by studying the medical records of DD cases admitted to three hospitals, (3) by studying prescriptions dispensed by three pharmacies and (4) by focus group discussions. The findings were analysed to evaluate the achievement of the Indonesian Diarrheal Diseases Control Program (CDD). ORT, avoiding antimotility drugs and appropriated feeding have been accepted and practiced by the providers in Palembang. The target of promotion now is to support the acquisition of these behaviours to be implemented as a routine habit of the providers and as a part of the ongoing system of health care delivery system. Specifically the danger of loperamide promotion to the policy on antimotility must be stressed. Rapid iv rehydration and avoiding surface precipitating agents have been accepted, but are not practiced consistently yet due to practical considerations. It seems that there is no impact at all of CDD towards the rate of antibiotic therapy in DD. Besides intensifying the campaign, enforcing group pressure, may be we have to elaborate more the perception of health care provider as a practitioner, and conforming the strategy of the CDD campaign towards the findings. Health education had not been practiced effectively yet. Morale and value system of the providers are important for the success of this program. In general the medical technic aspect of the CDD has been accepted by the providers, but there is still a lot to do in communicating them to be adopted as an effective behaviour. PMID- 1896194 TI - Umbilical cord length and intra uterine wellbeing. AB - The length of the umbilical cord was studied in 179 Indonesian newborns to determine the normal range of cord length and its influence on the occurrence of intrapartum complications such as meconium stained amniotic fluid, asphyxia and entanglement of the cord around the fetus. The authors also attempted to investigate whether unfavourable intra uterine conditions could influence cord length. Therefore a correlation between cord length, sex, gestational age, birthweight and head-circumference was sought. The mean length of the umbilical cord was 52.2 cm., with a S.D. of 10.2 cm, ranging from 31-100 cm. Male infants had significantly longer umbilical cords than females (p = 0.02). The risk of complications increased parallel with cord length. PMID- 1896195 TI - Nutritional status in childhood thalassaemia at the Department of Child Health University of North Sumatera Dr. Pirngadi Hospital Medan. AB - A-10 year (June 1979 to May 1989) study on the nutritional status of children with thalassaemia was done. The number of patients was 131; 75 (57.25%) were males and 56 (42.75%) females. A study on nutritional status by the age group was performed in 123 cases at the first diagnosis. The incidence of malnourished children over 1 year of age was significantly higher than in below 1 year of age cases (p less than 0.05). PMID- 1896196 TI - Acute hepatitis at the Department of Pediatrics, School of Medicine, University of North Sumatra/Dr. Pirngadi Hospital Medan. AB - A retrospective study was done during 1984-1988 in the pediatric ward of Dr. Pirngadi Hospital revealing 41 cases of acute hepatitis, consisted of 61.0% boys and 39.0% girls. The majority of patients were below five years of age (68.3%). There were 37.1% cases with malnutrition. The common symptoms were fever, jaundice, vomiting and dark urine. On laboratory examination there were 10 cases with positive HBs Ag. Accompanying diseases were malnutrition, bronchopneumonia, anemia, bronchitis and pulmonary tuberculosis. A total of 63.4% of patients were healed, 29.3% discharged against medical advice and 7.3% died because of bronchopneumonia and hepatic coma. PMID- 1896198 TI - The influence of pyridoxin in the treatment of tetanus neonatorum. AB - During a 2-year-period (1988-1990) 31 patients with tetanus neonatorum were recruited for this study. The patients were divided into 2 groups: The first group (15 patients) was treated with ATS injection, oral metronidazole and amoxycillin, and diazepam suppositoria. The second group (16 patients) was treated with the same regimen, as the first group plus pyridoxin injection 100 mg on the first day followed by 25 mg orally on the next days. There was no statistical difference in the two groups concerning the gestation period, sex, severity of the disease (p greater than 0.05), place of delivery (all at home) and mode of delivery delivered by traditional midwife/dukun). The mortality of the first group (without pyridoxin) was 60% and the second (with pyridoxin) 37.5% (p less than 0.05). PMID- 1896197 TI - Spectrum of asthma in children visiting the outpatient clinic of the subdivision of allergy and immunology. AB - A retrospective study on clinical and laboratory findings was conducted in 104 children with asthma visiting the Outpatient Clinic, Subdivision of Allergy and Immunology, Department of Child Health, Dr. Cipto Mangunkusumo General Hospital, Medical School, University of Indonesia, Jakarta. This study revealed that the proportion of asthma in males was greater than in females with the ratio 1.36:1. The age ranged from 8 months to 14 years with a mean age of 6.72 years. The majority of the children (70.2%) had the age of onset of asthma under 5 years, and the highest percentage was between 2-4 years (45.2%). The author thinks that this may be due to the upper respiratory tract infections, which are frequently found in this age group of children and may precipitate asthma in certain individuals. There was no significant correlation between the duration of breast feeding and the age of onset of asthma, without considering strict avoidance of formula or solid food. The majority of the children in this study (95.2%) had positive family history of atopy and 79.80% had family history of asthma. This supports the opinion that asthma is inherited. Thirty nine out of 104 children (37.5%) also suffered from other allergic manifestations and was mostly urticaria. It seems that patients with asthma tend to have other allergic diseases. The percentage of increased serum IgE level in pure asthma was 21.87% while increased eosinophil count 36.1%. The majority of the children in this study (92.8%) showed positive prick test. It seems that normal IgE serum level and normal eosinophil count did not rule out the presence of allergic asthma. The percentage of increased level of serum IgE and peripheral eosinophil count increased with the presence of ascariasis and other allergic manifestations. The majority of the patients tested (64 out of 60 patients) showed positive skin prick test against at least one allergen, the three leading percentages were against house dust (75%), animal epithelia (70.1%) and house dust mite (54.7%). It seems that the majority of our children with asthma were allergic and the most involved allergen was aeroallergen (inhalan). PMID- 1896200 TI - Cancer pain classification: a controversial issue. PMID- 1896199 TI - Myotonia congenita (Thomsen's disease) report of five cases in a family. AB - This report describes 5 out of 8 siblings who were the first cases of myotonia congenita diagnosed in our department. The parents were first cousins. Neither the parents, nor the other family members have myotonia. The affected siblings 4 boys and 1 girl, all showed a very typical myotonia especially after prolonged rest, and it could be worked off with continuing activity. They had a muscular looking body or a herculean proportion. The diagnosis were based upon family history, clinical findings of percussion myotonia, had grip myotania, prominent muscular hypertrophy and confirmed by electromyographic examination revealing myotonic discharges. Since there were some functional impairments, these patients were treated with diphenylhydantoin and then with quinine sulphate, with good results. The patients related parents were much likely to be heterozygous for the same harmful recessive genes, because they had common ancestor. The role of marriage counseling is important in this kind of inherited disease, to prevent the occurrence of this inherited disorder in the next generations. PMID- 1896201 TI - The effects of induced mood on laboratory pain. AB - Sixty-five subjects experienced 2 cold pressor immersions. Following the initial immersion, subjects participated in the Velten mood induction procedure by reading either depressive, neutral or elative statements. The sensory discriminative response to pain was measured by ratings of pain, and the affective-reactive response to pain was measured by pain tolerance. Pain tolerance, but not pain ratings, were affected by mood inductions with subjects in the depression condition shortening their tolerance times more than the subjects in the neutral condition and the subjects in the elative condition increasing their tolerance times. PMID- 1896202 TI - Comments on 'psychosocial correlates of temporomandibular joint pain and dysfunction' by R.F. Schnurr, R.I. Brooke and G.B. Rollman. PMID- 1896203 TI - The importance of monitoring tail-skin temperature in measuring tail-flick latency. PMID- 1896204 TI - Glycerol injection into the trigeminal ganglion provokes a selective increase in human cerebral blood flow. AB - Fourteen patients suffering from idiopathic trigeminal neuralgia (refractory to medication) were treated by injection of glycerol into the trigeminal ganglion. The changes in cerebral blood flow (CBF) after glycerol injection were quantified by intravenous 133Xe emission tomography. There was a significant 11% (P less than 0.01) increase in ipsilateral CBF and an 8% (P less than 0.05) increase in contralateral CBF 1 h after glycerol injection. The interhemispheric difference was significant (P less than 0.05). The increase was significantly greater in the ipsilateral internal carotid territory, in the anterior cerebral artery and middle cerebral artery territories (superficial (P less than 0.05), deep territories (P less than 0.001]. We suggest that these changes are due to the release of substance P and/or calcitonin gene-related peptide, from terminals of the trigeminal-vascular system during glycerol injection. PMID- 1896205 TI - Intravenous phentolamine test: diagnostic and prognostic use in reflex sympathetic dystrophy. AB - In some patients, ongoing and evoked neurogenic pain is relieved by pharmacological or destructive block of the sympathetic innervation of the affected part. In others, sympatholysis is ineffective. The present report shows that these two groups of patients can be distinguished by a safe and simple diagnostic test. Individuals in whom the pain was transiently relieved by intravenous phentolamine (Regitine) were very likely to respond favourably to subsequent sympatholytic treatment with i.v. regional guanethidine. Individuals in whom the phentolamine test was negative did not enjoy pain relief from this type of sympatholysis. PMID- 1896206 TI - The effect of streptokinase on chest pain in acute myocardial infarction. AB - Treatment with intravenous streptokinase is known to restore blood flow to the ischaemic myocardium in patients with acute myocardial infarction. However, little is known about its effect on chest pain. In a retrospective cohort study, 76 patients treated with streptokinase were compared to 76 patients not treated with streptokinase. All patients had acute myocardial infarction and less than 6 h of cardiac symptoms. Patients treated with streptokinase had a significantly lower need for nicomorphine (median 20 mg) than patients not treated with streptokinase (median 41 mg). Correspondingly, the median duration (3.5 h) of pain was reduced significantly in patients treated with streptokinase compared to patients not treated (24 h). We conclude that intravenous streptokinase given in the acute phase of myocardial infarction is effective in reducing the duration of cardiac chest pain. PMID- 1896207 TI - Can anxiety help us tolerate pain? AB - It was hypothesized that anxiety which is relevant to the source of pain exacerbates pain, whereas anxiety which is irrelevant to the source of pain reduces the experience of pain. Female subjects were given either high or low anxiety provoking information about a cold pressor task (relevant anxiety) or high or low anxiety provoking information about a potential shock (irrelevant anxiety). Subjects were then exposed to the cold pressor. The results demonstrated that subjects who were highly anxious about the cold pressor reported experiencing the most pain. Subjects who were highly anxious about the shock reported the least pain and reported significantly less pain than subjects who were highly anxious about the cold pressor. These findings clearly demonstrate that the relationship between anxiety and pain is not always positive or unidirectional. PMID- 1896208 TI - Confirming the theoretical structure of the McGill Pain Questionnaire in acute clinical pain. AB - Based upon a tripartite theoretical model of pain, the Pain Rating Index (PRI) of the McGill Pain Questionnaire (MPQ) continues to be one of the most frequently used instruments to measure clinical pain. Although a number of exploratory factor analytic studies have failed to consistently support the theoretical structure of the instrument, one previous confirmatory factor analytic study of chronic pain did statistically support the a priori model. Because it has been suggested that acute pain may not involve the same dimensions as chronic pain, this study provided a direct test of the theoretical structure of the MPQ through multi-sample confirmatory factor analysis (CFA) using data provided by women experiencing pain during labor (n = 185) and women experiencing acute postoperative pain (n = 192). Results of the LISREL CFA analysis indicated that the a priori, 3-factor, oblique model originally proposed by Melzack provided the most parsimonious representation of the data across the 2 samples of acute pain. PMID- 1896209 TI - The development of a Norwegian pain questionnaire. AB - The study was undertaken to develop a multidimensional measuring instrument for pain in the Norwegian language. The McGill Pain Questionnaire (MPQ) was used as a model as it is a valid and reliable tool for pain measurement in English speaking countries. A series of steps were taken to develop a Norwegian pain questionnaire: (1) words describing pain were derived from 95 subjects (patients, students and health personnel); (2) 10 subjects allocated pain descriptors into groups; (3) 36 college student validated the word groupings; (4) 72 patients graded the words contained in each group according to intensity; and (5) the reliability of group items was tested. The study demonstrated that there are many descriptors of pain in the Norwegian language. The final version of the Norwegian pain questionnaire consisted of 106 pain descriptors divided into 18 groups. Validity of the classifications as well as reliability of the words was demonstrated. The actual value of the Norwegian pain questionnaire as a measuring instrument has not yet been documented. PMID- 1896210 TI - Effects of lateral reticular nucleus stimulation on trigeminal sensory and motor neuron activity related to the jaw opening reflex. AB - The effects of lateral reticular nucleus (LRN) stimulation on the responses to tooth pulp (TP) stimulation of neurons located in the trigeminal (V) sensory (39 units) and motor (33 units) nuclei were assessed in anesthetized rats. Only neurons which responded to TP stimulation with bursts of spikes that were in a constant temporal relationship with the digastric EMG signal were studied. The LRN-stimulating electrodes were positioned at optimal sites to suppress the TP evoked jaw-opening reflex (JOR) recorded simultaneously with the neuronal activity related to it. It was found that: (1) the neurons in the V nucleus oralis responded to TP stimulation with 3-8 msec latency excitatory responses that were suppressed during LRN conditioning stimulation with a time course comparable to that of the JOR suppression, and (2) the neurons in the V nucleus motor responded to TP stimulation with 5-15 msec latency excitatory responses. This activity was suppressed during LRN-conditioning stimulation with a time course that parallels the inhibition of the activity of nucleus oralis neurons and of the JOR. However, assuming that the excitatory interneurons for the V motoneurons are located in the nucleus oralis, the suppression of this input by LRN may account for the lack of response in V motor neurons. Thus, we suggest that LRN inhibits the TP-evoked JOR by acting on the sensitive afferent limb of the reflex. PMID- 1896211 TI - Preparative surgery enhances the direct spinal actions of three injectable anaesthetics in the anaesthetized rat. AB - In this study we have investigated the influence of preparative surgery on the potency with which a range of injectable anaesthetics depressed nociceptive withdrawal reflexes in anaesthetized, spinalized rats. Drug effects were compared on 2 different preparations, each requiring differing degrees of preparatory surgery. Recordings were made in each case of unitary motoneurone responses to controlled noxious stimuli. The dose-dependent effects of the general anaesthetics alpha-chloralose (20-80 mg/kg i.v.) and alphaxalone/alphadolone (0.5 2 mg/kg) and of the dissociative anaesthetic ketamine (0.5-16 mg/kg) were studied. When the degree of surgical intervention was increased, the reflex response to a uniform mechanical pinch stimulus was facilitated. This enhanced response was more susceptible to the reflex depressant actions of all the compounds studied. PMID- 1896212 TI - A novel technique for the evaluation of mechanical pain and hyperalgesia. AB - We describe a new technique which is useful for the evaluation of mechanically induced pain and hyperalgesia. Light metal cylinders are guided and accelerated in a barrel. On impact against the skin they elicit a brief sensation of pain. This method allows the application of a wide range of controllable innocuous and noxious impact velocities of the cylinder at variable stimulus repetition rates. The system is sufficiently flexible to stimulate perpendicularly any skin area and to move rapidly to adjacent target regions if desired. Psychophysical testing using magnitude estimation techniques revealed that pain thresholds were normally distributed. Over a wide range of stimulation intensities monotonically increasing stimulus response functions were obtained. Repeated testing showed a good intra-individual reproducibility of both threshold and supramaximal pain ratings. The method was also useful in determining the time course of pain and mechanical hyperalgesia following a brief painful stimulus. We conclude that the new technique is useful for evaluating psychophysical stimulus response functions of mechanically induced pain and its changes following tissue injury. This technique may also hold some promise in quantifying altered pain sensitivity in patients. PMID- 1896213 TI - Stress analgesia: the opioid analgesia of long swims suppresses the non-opioid analgesia induced by short swims in mice. AB - In mice, room temperature swimming for as short a period as 15 sec has been found to induce a non-opioid analgesia with a time course of 10-12 min. As the duration of the swim is increased, an opioid analgesia develops with a longer persistence (25-30 min); the development of the opioid analgesia appears to suppress the expression of the non-opioid analgesia so that none of the latter is evident after 3 min swims. The characteristics of the tail-flick nociceptive test are also described. PMID- 1896214 TI - The acute effects of amputation on peripheral trigeminal afferents in Gallus gallus var domesticus. AB - In 10 adult Brown Leghorn hens electrical recordings were made from sensory afferent fibres in dissected nerve filaments of the trigeminal nerve innervating the lower beak. The lower beak was subjected to partial amputation using a heated blade and recordings were taken before, during and after amputation. Amputation produced a massive injury discharge which lasted from 2 to 48 sec (mean 15 sec). There were still active units present in the filament with receptive fields proximal to the site of cautery and for 90 min after amputation no abnormal activity was recorded in these units and no abnormal spontaneously active units were observed. From 90 to 270 min post-amputation single units were dissected and of the 93 rapidly adapting mechanoreceptors, 78 slowly adapting mechanoreceptors, 23 mechanothermal (polymodal) nociceptors, 7 cold and 3 warm thermoreceptors none showed any abnormal pattern of response to cutaneous stimulation. This absence of change in the peripheral neural input following amputation could provide a mechanism to explain the absence of observed pain immediately following partial beak amputation. PMID- 1896215 TI - The expiratory muscles in tetraplegia. PMID- 1896216 TI - The experimental basis for early pharmacological intervention in spinal cord injury. PMID- 1896217 TI - Toward a health services research capacity in spinal cord injury. AB - Health services research (HSR) is the research field that seeks to examine systematically the organisation, provision, and financing of health care services. There currently is only a rudimentary HSR capacity in the area of spinal cord injury (SCI). To a large extent, the HSR community has not addressed issues concerning persons with SCI, and the disability research and medical rehabilitation communities have not considered issues of HSR that affect the SCI population. However, due to recent changes in (1) the clinical management of SCI; (2) the expectations of persons with SCI, and (3) health care delivery and finance, the time is now ripe for the development of a HSR capacity in SCI. This article summarises current efforts at HSR in SCI in the United States, which have been primarily in the areas of trauma care and medical rehabilitation. It considers an agenda for future health services research in SCI, which must include research on post-rehabilitation health care and personal assistance needs. Finally, this article suggests strategies for developing a comprehensive HSR capacity in SCI. PMID- 1896218 TI - Pressure sore carcinoma: a late but fulminant complication of pressure sores in spinal cord injury patients: case reports. AB - The development of a pressure sore carcinoma in scars of spinal cord injury patients is a rare event (less than 0.5%) and occurs late (more than 30 years after the spine injury) but the prognosis is very poor. Five cases are reported and different aspects are reviewed: anamnesis, clinical features, and follow-up studies. The association of surgery and radiotherapy is usual but is not very successful. Local-regional chemotherapy and a better approach concerning immunological mechanisms may improve survival. Scar prevention and surgical management of chronic scars treated unsuccessfully by medical methods are the best means to prevent malignant changes in chronic pressure sores. Biopsy should be mandatory for all pressure sores after the first decade. PMID- 1896219 TI - The value of magnetic resonance imaging (MRI) in the follow-up management of spinal injury. AB - Twenty-seven patients with spinal injury have been studied with follow-up Magnetic Resonance Imaging (MRI). MRI has helped (a) to determine the extent of cord injury; (b) to detect continuing compression to the spinal cord; (c) to discover unexpected pathologies and most importantly (d) to detect the development of post traumatic syrinx. MRI was most valuable in patients with post traumatic syrinxes to evaluate any changes in the size, and, in those who had a shunting procedure, to assess the efficacy of the procedure. MRI also aided in planning complicated one stage operations by giving a 'complete' picture of the injury inflicted to the vertebrae, soft tissue structures and the spinal cord. As well as advantages in clinical audit it makes financial sense. It provides more information than CT myelography and is non-invasive. When compared to the cost of neurological deterioration it is much more cost effective to follow-up spinal injury patients with MRI. It is the authors' contention that after the acute phase all patients with spinal injury should have at least one MRI. PMID- 1896221 TI - Myotonic dystrophy and traumatic quadriplegia: case report. AB - A thirty-year-old man with traumatic quadriplegia, was also found to have weakness above the level of the injury. He had facial weakness, difficulty in swallowing, and recurrent respiratory problems. A diagnosis of myotonic dystrophy was supported by examination of his sister. The problems of diagnosis, and the implications of the diagnosis on the management of the patient with myotonic dystrophy and a spinal injury are discussed. PMID- 1896220 TI - Differentiation of spinal damage through compression mechanism. AB - In the years 1965 to 1986, 986 patients with spine fractures caused by compression were treated at the Rehabilitation Clinic. This communication presents an analysis of those patients, taking into account the significant differences between typical compression fractures and explosion fractures, the latter are, as a rule, complicated by considerable or complete spinal cord damage. The author has pointed to the differences in the indication for surgery, different prognosis and significantly different results of treatment. The author is of the opinion that, due to those differences, the two kinds of spinal fractures should be considered separately with regard to the analysis of the mechanism of injury, the prognosis and the assessment of the results of treatment. PMID- 1896222 TI - Osteonecrosis: an overuse injury of the shoulder in paraplegia: case report. AB - The shoulder of the wheelchair dependent paraplegic is subject to overuse injury with subsequent pain. The major overuse syndromes observed include soft tissue injuries and secondary degenerative arthritis. This report presents a case in which bilateral osteonecrosis of the humeral heads was found to be the source of pain in the shoulders of an active paraplegic without any evidence of disease or medical treatment associated with the development of osteonecrosis. Osteonecrosis should be entertained in the differential diagnosis of overuse injuries of the shoulder in paraplegia. PMID- 1896223 TI - Sometimes it's tough to be a parent. PMID- 1896224 TI - Common behavior problems and the pediatrician. PMID- 1896225 TI - Sleep learning: the first four months. PMID- 1896226 TI - Toileting problems in children. PMID- 1896227 TI - Primary nocturnal enuresis: current concepts about an old problem. AB - In summary, all children and families who present with nocturnal enuresis should be offered education, reassurance, and ongoing support as a premier component of any treatment regimen. At the same time, the family should be informed about all the treatment options that exist with a goal of tailoring the specific treatment to the individual patient. In most cases, this approach will lead to child, family, and physician satisfaction. PMID- 1896228 TI - Treating attention-deficit hyperactivity disorder: medication and behavior management training. PMID- 1896229 TI - Oppositional behavior in children. AB - Early intervention for children's oppositional behaviors is likely to be more effective than later treatment. The term oppositional includes a variety of noncompliant and aggressive behaviors that can be assessed with clinical interviews, rating scales, direct observation, and self-report measures. Treatment of children's oppositional behaviors is best approached from a parent training perspective. Parent training approaches have produced significant improvements in children's behavior, although far more research has been devoted to discipline than to identifying the more salient features of time-in. Recent advances in assessment and treatment are notable, but continued efforts are needed to determine the optimal treatments that produce the best social and psychological outcomes for children and adolescents. PMID- 1896230 TI - Pulmonary manifestations of HIV infection in children. AB - We retrospectively reviewed the spectrum, course, and outcome of pulmonary diseases in 66 children with AIDS, hospitalized between 1982 and 1988, prior to the use of zidovudine. Fifty-two of the 66 (79%) patients developed pulmonary problems. In fifty-two percent of all patients, a pulmonary problem was the first symptom of HIV infection. The most common respiratory illness requiring hospitalization was an episode of respiratory distress with normal PaO2 and unchanged X-ray with a 9.7 +/- 6.8 days mean duration of hospitalization. Bacterial pneumonia, Pneumocystis carinii pneumonia (PCP) and pulmonary lymphoid hyperplasia/lymphoid interstitial pneumonia occurred in 30%, 32% and 22% of the patients, respectively. Bacterial pneumonia and PCP were associated with a high mortality rate. Sixty-eight percent of the patients died within 24 months of the onset of pulmonary disease. In 50% of the children, pulmonary disease was a primary cause of death. The results of this study can be useful in developing prospective studies for the prevention and treatment of pulmonary complications of HIV infection. PMID- 1896231 TI - Relationship between response to inhaled salbutamol and methacholine bronchial provocation in children with suspected asthma. AB - Fifty children (27 females, 23 males) ages 6-15 years who were referred for evaluation of suspected asthma had baseline FEV1 and FEF25-75 of greater than or equal to 80% and FEF50 greater than or equal to 70% of predicted values. All had these tests repeated on the same day, after inhaling salbutamol. On a subsequent day PC-20 (methacholine) was determined as an index of bronchial hyperreactivity (BH). Fourteen age-matched healthy children (6 females, 8 males) were studied in a similar manner. There was no significant relationship between the PC20 and the change in FEF25-75 or FEF50 following salbutamol. There was a negative correlation between the initial FEV1 (% predicted) and the percent change in FEV1 following salbutamol (P less than 0.01). An increase in FEV1 of greater than 6% occurred in 7/12 (58.3%) patients with PC20 less than or equal to 0.25 mg/mL (Group I); in 7/24 (29.2%) patients with PC20 = 0.26-2.0 mg/mL (Group II); in only 1/14 (7.1%) patients with PC20 greater than 2.1 mg/mL (Group III) and in none of those asymptomatic (control) children with PC20 greater than 8.0 mg/mL (Group IV). All subjects who had a change in FEV1 greater than 6% after salbutamol had a PC20 less than 8 mg/mL and this test detected the majority of patients with severe BH. However, although the sensitivity of the test was 100%, the predictive value was only 36%. We conclude that in the presence of a normal baseline FEV1 a change of greater than 6% following salbutamol inhalation is indicative of bronchial hyperreactivity. PMID- 1896232 TI - Epidemiology of cystic fibrosis in Latin America: preliminary communication. AB - We conducted a retrospective study of 743 patients with cystic fibrosis (CF), covering the 1979-89 period in 4 Latin American (LA) institutions to evaluate the clinical features of the disease. The review, although dealing only with patients referred to, or diagnosed at these institutions may be considered to comprise the majority of patients living in these areas. Diagnosis was confirmed by the sweat test in all cases. There was a slight predominance of males, (61.0%) mainly in the Brazilian group. The mean age at diagnosis was over 3 years. This was similar to the mean age at admission. Almost half of the patients were still alive at follow-up, but their mean age was low (6.4 years in Brazil, 7.4 in Chile, 9.6 in Mexico, and 11.3 in Argentina). Mean age at death ranged from 3.1 years (Chile) to 8.7 years (Argentina). The highest proportion of living patients was in Chile (71.4%) and the lowest in Argentina (33.8%). Survival curve comprised 15 years after diagnosis for the Argentinian group, compared to 6 years for the remaining groups. Fifty percent of the patients lived 6-7 years after diagnosis in Argentina, 4-5 years in Mexico and Chile, and 3 years in Brazil. Among Argentine patients 39.2% survived to 10 years of age, and 18% to 15 years. These findings suggest that CF is not rare in LA but extensive epidemiological studies are needed to obtain accurate figures on the magnitude of the problem. PMID- 1896233 TI - Bacterial infection in under school age children with expiratory difficulty. AB - Serological evidence of bacterial infection was prospectively studied in less than 6 years old patients during 188 acute episodes of expiratory difficulty requiring hospital treatment. Such evidence indicated by antibody or antigen assays was found in 40 patients (21%). Streptococcus pneumoniae was identified in 25 cases; antigenemia was found in 10, antigenuria in 2 and seroconversion in 14 cases. Seroconversion to nontypable Haemophilus influenzae was found in 9 and to Branhamella catarrhalis in 2 cases. Seroconversion to Chlamydia spp. was demonstrated in 8 patients, but specific tests for C. trachomatis were negative. C-reactive protein was over 40 mg/L in 35 patients (19%); serological evidence of bacterial infection was present in 14 and absent in 21 of them. Thus, either serological evidence of bacterial infection or an elevated C-reactive protein was found in 61 of the 188 cases (32%). We conclude that bacterial infection is commonly associated with acute wheezing in children under school age. We suggest that bacterial, as well as viral, infections may trigger an acute obstructive attack in children with reactive airways. PMID- 1896234 TI - Luminal surfaces of fetal rat alveolar type II and Clara lung cells react with antibody to Heymann nephritis antigen. AB - We have used affinity purified antibody, which reacts with the renal antigen gp600, to examine the immunoreactivity of pulmonary cells in the quick frozen lung tissue of fetal rats. On immunoelectron microscopy, we found that the reaction was specifically localized to the luminal surfaces of Clara cell and, as previously reported, to alveolar type II cell (ATII) membranes. No immunoreaction was seen on or in type I cells, endothelial cells or any other lung or blood cell. These studies suggest that the anti-gp600 immunoselection can be used as a marker to identify and quantify Clara and ATII cells in rat lung tissue. PMID- 1896235 TI - Predicted values for lung diffusing capacity in healthy children. AB - Lung diffusing capacity was measured in 92 healthy Caucasian children (52 boys and 40 girls), ranging in age from 6 to 17 years, using the single breath carbon monoxide technique (DLCO). Multiple regression equations were developed to predict the DLCO value. Standing height, gender, weight, and age were significant factors in the prediction of DLCO. Sitting height was not a significant covariate when standing height was in the model, but it could replace standing height in the equation. Equations are presented for the calculation of predicted DLCO in children based on standing or sitting height, age, sex, and weight. PMID- 1896236 TI - Cold air challenge of airway reactivity in children: a correlation of transcutaneously measured oxygen tension and conventional lung functions. AB - For pharmacological challenges, a correlation between the induced changes of the transcutaneously measured oxygen tension (PtcO2) and of conventional pulmonary function tests (PFTs) has been documented. We performed a 4-minute cold air challenge (CACh) in 17 children with bronchial asthma under continuous monitoring of PtcO2, and correlated observed changes with CACh-induced alterations of conventional PFTs. PtcO2 decreased significantly with CACh (from 86 +/- 10 mmHg to 66 +/- 14 mmHg, P less than 0.001), but returned to near-baseline within the next 30 minutes. PFTs changed with a similar pattern; the closest correlation was found between the CACh-induced fall of PtcO2 and Delta-FEV1 (r = 0.833, P less than 0.001). Changes of FVC, PEF, and Vmax50 correlated significantly as well. PtcO2 can complement or substitute for conventional PFTs in assessing the response to CACh in children. PMID- 1896237 TI - Malnutrition and lung growth. PMID- 1896238 TI - Effect of vascular puncture on blood gases in the newborn. AB - Continuous monitoring methods have shown changes of oxygenation in neonates during various procedures. However, actual changes in blood gases during vascular punctures have not been reported. We studied the effect of vascular puncture on arterial blood gases during routine venipuncture in 17 neonates who had indwelling arterial catheters. Arterial blood gases were analyzed before, during, and following recovery from venipuncture. Ventilator settings were not changed during the study, though oxygen concentration (FiO2) was adjusted as indicated by continuous PO2 or saturation monitors. During venipuncture, there was a significant fall in PaCO2 from 38 +/- 5 to 32 +/- 7 mmHg (P less than 0.0001) and in PaO2 from 75 +/- 21 to 58 +/- 23 mmHg (P less than 0.0001). Following venipuncture, both values returned to baseline. The results of this study imply that blood gases obtained by intermittent arterial sticks may provide data that do not accurately reflect the neonates' respiratory status. PMID- 1896239 TI - Comparison of three methods for measuring respiratory mechanics in ventilated children. AB - Continuous measurements of airway pressure, gas flow, and tidal volume were made in 22 mechanically ventilated children, both during steady state conditions and following airway occlusion at end-inflation. For each child, three methods of analyzing the stored data were used to generate values of respiratory system compliance and resistance: 1) end-inspiratory hold technique (Bone: Respir Care 28:597, 1983; Rossi et al. Am Rev Respir Dis 131:672, 1985); 2) constant flow technique (Rossi et al. J Appl Physiol 58:1849, 1985; Suratt et al. J Appl Physiol 49:1116, 1980); and 3) multiple linear regression (Roy et al. Comput Biomed Res 7:21, 1974; Bhutani et al. Pediatr Pulmonol 4:150, 1988). In the absence of an accepted standard, we used the inspiratory hold technique as a reference. All methods gave comparable values for respiratory mechanics over a wide clinical range. However, multiple linear regression was the most convenient of the three: it can be automated and continuously displayed, there is no subjective input, values are taken through the respiratory cycle, and it is completely noninvasive. We also found that respiratory system resistance was largely a measure of endotracheal tube resistance and that respiratory compliance is a more sensitive monitor of lung function in intubated children. PMID- 1896240 TI - Doppler echocardiographic evaluation of pulmonary artery pressure in pneumonia of infants and children. AB - Previously, there was insufficient evidence to confirm that pneumonia in infants and children might lead to the development of pulmonary hypertension. Recently, it has been shown that acceleration time corrected for heart rate (ATc) and the ratios of right ventricular preejection period to right ventricular ejection time (RPEP/RVET) and of right ventricular preejection period to acceleration time (RPEP/AT) derived from Doppler echocardiography correlated well with pulmonary artery pressure (PAP). To approach PAP in patients with infantile pneumonia, we measured RPEP/RVET, RPEP/AT, and ATc in 105 infants and children with pneumonia and in 17 controls, using a commercially available 2-dimensional echocardiograph (Toshiba SSH-40A) with SDS-21B Doppler unit. An increase of varying degrees in both ratios and ATc was noted during acute illness and significant differences in ratios RPEP/RVET and RPEP/AT were found among patients with mild, moderate, and severe disease. This suggested that PAP increased to different extents in the acute stage of illness and that the degree of increase was related to the severity of disease. PMID- 1896241 TI - Plasma cell granuloma of the lung: associated laboratory findings and ultrastructural evidence of inflammatory origin. PMID- 1896243 TI - Congenital pulmonary lymphangiectasia. PMID- 1896242 TI - Recurrent respiratory infections in a child with fucosidosis: is the mucus too thin for effective transport? AB - Fucosidosis is caused by a deficiency of the lysosomal enzyme alpha-L-fucosidase (ALF) leading to an accumulation of glycoproteins in a variety of cells. Infants and young children with this disorder are prone to recurrent sinus and pulmonary infections and often die of pneumonia. We studied the mucociliary and systemic immune function in a 6 year old girl with fucosidosis and recurrent respiratory infections. All measurements of systemic immune function were normal. Sweat chloride was normal when measured on angiokeratotic skin but was greater than 65 mg/L on uninvolved areas. During the placement of tympanic ventilation tubes, tracheal mucus was gently aspirated and a mucosal biopsy was taken. Tracheal mucus transport was not measured. The biopsy material was examined under phase contrast microscopy and revealed ciliated cells with apparently normal beating. TEM of these cells showed a characteristic pattern of vacuoles in the cytoplasm as described in other tissues from patients with fucosidosis. Ciliary ultrastructure was normal. Mucus viscoelasticity was measured in a magnetic microrheometer. The loss tangent was 2 SD above the mean for normal mucus and mechanical impedance was about 2 SD below the mean. These changes are similar in direction but double in magnitude to what has been described with methacholine administration in dogs. The high compliance of the mucus may be due to incomplete assembly of mucus glycoprotein or to decreased secretion of glycoproteins in respiratory secretions. This leads to mucus that is abnormally watery and thus difficult to clear from the airway. PMID- 1896244 TI - On the effect of altering smooth muscle tone in patients with tracheomalacia. PMID- 1896245 TI - Mucosal antibodies to Haemophilus influenzae type b capsular polysaccharide. AB - Levels of salivary antibodies directed against Haemophilus influenzae b (Hib) capsule, measured by ELISA and standardized to the total salivary IgA, were compared among 57 patients with Hib infections, 117 household and 49 day care contacts of patients, and 53 control individuals with no known contact with Hib. Nineteen of the household or day care contacts were throat or nasopharyngeal culture positive for Hib. Eighty % of evaluable patients had polyribosylribitol phosphate (PRP)-specific IgA in their saliva, compared with 36% of contacts who were throat or nasopharyngeal culture positive for Hib, 53% of contacts who were throat or nasopharyngeal culture negative for Hib, and 30% of control children. In patients, no correlation between age and level of salivary anti-PRP antibody was seen, but patients less than 3 y old were more likely to have these antibodies than were older patients. Salivary PRP-specific IgA antibodies, associated with either Hib colonization or PRP vaccination, tended to decline over time. Thus, PRP-specific IgA antibodies can be identified in the saliva of children over a wide age range, including those colonized with Hib or vaccinated with PRP, but these antibodies appear to decline after antigenic stimulation ceases. PMID- 1896246 TI - Gender-related differences in iron absorption by preadolescent children. AB - In a study of absorption of iron from meals by preadolescent children (Tanner stage 1), we had noted that erythrocyte incorporation of the extrinsic iron label was somewhat greater by girls than by boys. Although the difference was not significant, the observation seemed to warrant further study. Study A: A precisely determined quantity of ferrous sulfate enriched with the stable isotope 58Fe was given without food to 15 boys and 15 girls (Tanner stage 1) after an overnight fast and was immediately followed by a dose of 70 mg of ascorbic acid. 58Fe enrichment of the erythrocytes was determined by inductively coupled plasma mass spectrometry at baseline and 14 and 42 d after administration of the 58Fe dose. Geometric mean erythrocyte incorporation of the 58Fe label was 35.2% of intake by boys and 45.0% of intake by girls. The difference was significant (analysis of covariance with serum ferritin as covariate, p = 0.035). Study B: Fifteen boys and 15 girls (Tanner stage 1) were fed a breakfast labeled with 58Fe. Geometric mean erythrocyte incorporation of the 58Fe label was 14.8% of intake by boys and 24.7% of intake by girls. The difference was significant (analysis of covariance with serum ferritin as covariate, p = 0.004). Because serum ferritin concentrations were similar in boys and girls, the gender-related difference in iron absorption (as reflected by erythrocyte incorporation of the label) does not appear to be explained by a difference in body stores of iron. We hypothesize that hormonal differences between boys and girls in Tanner stage 1 favor iron absorption by girls. PMID- 1896248 TI - Dissociation between the effects of theophylline and caffeine on premature airway smooth muscles. AB - Xanthine derivatives relax adult airway smooth muscle (ASM). To determine whether caffeine and theophylline relax preterm ASM contracted by acetylcholine, 27 tracheal rings obtained from seven preterm lambs (120-135 d gestation) were studied. ASM was contracted using 10(-5) M acetylcholine (control) after the muscle was stretched to the length at which maximum active tension was developed isometrically. Concentration-effect curves for each xanthine were obtained by cumulative addition of the drug. Theophylline produced a significant decrease (p less than 0.001) in active tension at each dose, whereas caffeine significantly increased (p less than 0.001) active tension at 10(-4) and 10(-3) M concentrations. Addition of caffeine and theophylline to previously uncontracted ASM did not alter tension. Thus, it appears that, in contrast to their effect on adult ASM, the xanthine derivatives caffeine and theophylline have differential effects on prestimulated ASM in preterm lambs. These findings raise important questions about various aspects of the current therapeutic use of caffeine and theophylline. PMID- 1896247 TI - The role of selenium nutrition in the development of neonatal rat lung. AB - Our study was designed to assess the role of selenium (Se) in development of neonatal lungs under conditions of normoxia and hyperoxia. Thirty-six female Sprague Dawley rats were bred and fed a Se-deficient (0.03 ppm Se) or a Se adequate (0.5 ppm Se) diet during pregnancy and lactation. At d 2 postpartum, 24 litters were randomly assigned to either high oxygen (greater than 95%) or air and were cross-fostered for 4 d. Lung weight was significantly enhanced in Se adequate pups and was not related to high oxygen or air exposure of either the pups or dams. Two types of histologic lesions were observed in the lungs of the pups: septal attenuation and interstitial inflammation. When reared in oxygen, all (17 of 17) Se-deficient pups had lesions. In contrast, only 60% (9 of 15) of Se-adequate pups were affected (p less than 0.01). Lung lesions also were more severe in Se-deficient pups. Se-deficient pups also displayed a significant degree of septal attenuation when reared in air. Se-dependent glutathione peroxidase activity in the pup lung was significantly elevated in response to hyperoxia and was unrelated to Se nutriture. No differences in activities of lung superoxide dismutase, catalase, and glutathione s-transferase were noted between Se-deficient and Se-adequate pups reared in air or high oxygen environments. These data indicate that Se has an important role in the development of neonatal lungs, a role that is even more pronounced during conditions of hyperoxia. The protective role of Se in developing lung tissue cannot be completely explained by enhanced glutathione peroxidase activity. PMID- 1896249 TI - The use of synthetic peptides in the formation of biophysically and biologically active pulmonary surfactants. AB - Synthetic pulmonary surfactants consisting of mixtures of phospholipids with synthetic peptides based on the amino acid sequence of human surfactant apoprotein SP-B were prepared. These surfactants were analyzed for their ability to lower surface tension on a pulsating bubble surfactometer and for their capacity to improve lung compliance and increase alveolar expansion in a fetal rabbit model of surfactant deficiency. The data demonstrate that several peptides, ranging from 17 to 45 residues in length, matching the carboxy-terminal sequence of the SP-B protein, when appropriately recombined with the phospholipid dipalmitoylphosphatidylcholine and phosphatidylglycerol (3:1), are capable of producing a synthetic surfactant with biophysical and biologic activity approaching that of human surfactant derived from amniotic fluid. PMID- 1896250 TI - In utero ventilation augments the left ventricular response to isoproterenol and volume loading in fetal sheep. AB - In its normal circulatory environment, the fetal left ventricle can maximally increase output less than 2-fold, in contrast to the nearly 3-fold increase that occurs at birth. Several studies have attributed this finding to fetal myocardial "immaturity," and speculated that there is a rapid maturation of the myocardium in the perinatal period. We investigated the importance of the circulatory environment itself, rather than myocardial immaturity, by measuring left ventricular output (LVO) during in utero oxygen ventilation and isoproterenol infusion. We studied seven near-term fetal sheep greater than or equal to 2 d after placement of intravascular catheters, an endotracheal tube, and an electromagnetic flow transducer around the ascending aorta. We measured hemodynamic variables in the presence and absence of all combinations of oxygen ventilation, isoproterenol infusion, and volume infusion. Baseline LVO was normal (133 +/- 27 mL.kg-1.min-1). Individually, oxygen ventilation (136 +/- 11 mL.kg 1.min-1, p less than 0.001) and isoproterenol (48 +/- 11 mL.kg-1.min-1, p less than 0.05) increased LVO significantly; volume infusion did not. Their cumulative effect increased LVO nearly 3-fold (to 387 +/- 98 mL.kg-1.min-1), similar to levels seen in the newborn lamb. Mean left atrial pressure increased above right during oxygen ventilation (from 0.05 +/- 0.54 kPa to 0.82 +/- 0.39 kPa, p less than or equal to 0.0001). We conclude that the previously observed limitation in maximal LVO in the near-term fetus is primarily caused by its circulatory environment rather than relative myocardial immaturity, and speculate that a prominent Starling response is uncovered by decreases in left ventricular afterload and right ventricular constraint. PMID- 1896251 TI - The end-systolic pressure-volume relationship in the newborn lamb: effects of loading and inotropic interventions. AB - Indices of global systolic performance of the newborn left ventricle exceed those of the adult, despite isolated tissue studies showing immature contractile mechanisms. To evaluate contractility in situ, we investigated the end-systolic pressure-volume relationship (ESPVR) by the conductance technique in nine newborn lambs. After percutaneous placement of catheters, we generated ESPVR by inferior vena cava occlusion, aortic occlusion, and volume infusion in two control states, during three levels of dobutamine infusion, and after propranolol. We performed linear and nonlinear regression analyses of the end-systolic points and derived the slope (Ees) and volume at 14 kPa pressure. We found that reliable ESPVR could be obtained in almost all inferior vena cava and aortic occlusions (50 of 51 in each), but in only 18 of 27 volume infusions. Overall, linear regressions adequately defined the ESPVR (75 of 102 were not statistically different than nonlinear regressions; of those different, the mean linear R2 was 0.934 +/- 0.048). By multiple regression analysis, neither Ees nor volume at 14 kPa significantly changed with dobutamine, but both changed after propranolol (23% less than control and 54% greater, respectively), supporting previous studies showing a limited contractile reserve in the newborn secondary to high resting beta-adrenergic tone. Neither Ees nor volume at 14 kPa was different between control states. However, Ees was 25% less steep when generated by inferior vena cava than by aortic occlusion. We conclude that the ESPVR can be generated reliably and reproducibly in the newborn lamb and is relatively linear and sensitive to changes in contractility, but that it is also sensitive to the technique of load intervention. PMID- 1896252 TI - Immunohistochemical study on perinatal development of rat superoxide dismutases in lungs and kidneys. AB - It has been reported that levels of antioxidant enzymes are low in fetal rat lungs and kidneys, and that they increase rapidly during late gestation. Among the antioxidant enzymes, both copper-zinc and manganese superoxide dismutases (CuZnSOD and MnSOD) are assumed to play a key role in protection against oxidative tissue injury. To determine the nature of the rapid perinatal increase in CuZnSOD and MnSOD, immunoenzyme staining was performed in the lungs and kidneys of fetal (d 18 and 20 of gestation) and neonatal (d 22) rats. The CuZnSOD and MnSOD in the homogenates were assayed by RIA, and they were found to be higher in the neonatal organs than in the respective fetal organs. The neonatal bronchiolar epithelium was stained for both CuZnSOD and MnSOD more intensely than the fetal one. The CuZnSOD staining in the neonatal alveolar wall was more intense than that in the fetal one. There was a significant reactivity for MnSOD in the neonatal, but not in the fetal, alveolar walls. In the kidneys, the reactivities for CuZnSOD and MnSOD were confined to the undifferentiated tubules. Although the tubules were increased in numbers in the neonatal kidneys, the intensity of the staining for both CuZnSOD and MnSOD was unchanged. The histochemical study disclosed that CuZnSOD and MnSOD increased in the kidneys in a manner different from that in the lungs. The low concentration of both CuZnSOD and MnSOD in the fetal lung tissues may contribute to the vulnerability to oxygen toxicity. Such changes in the concentrations in specific tissues were not delineated in the kidneys. PMID- 1896253 TI - Caffeine acetylator phenotyping during maturation in infants. AB - Caffeine acetylator phenotype was studied during maturation in 54 8- to 447-d-old children hospitalized for minor disease (group A) and in five 3- to 630-d-old children with Pierre Robin syndrome (group B). In group A, the children received 2.5 mg/kg caffeine orally once between birth and 15 mo. Group B patients were chronically treated with caffeine (2.3 to 15.8 mg/kg/d) for prevention of apneas, and the acetylator phenotype was serially determined. Phenotyping was performed on a spot urine sample collected 2-6 h after drug administration. Caffeine metabolites [5-acetylamino-6-formylamino-3-methyl uracil (AFMU), 1 methylxanthine, 1-methyluric acid, 1,7-methyluric acid, and 1,7-methylxanthine] were measured using HPLC. Acetylator phenotype was determined on the basis of AFMU/1-methylxanthine (ratio 1) and AFMU/AFMU + 1,7-methyluric acid + 1 methylxanthine + 1,7- methylxanthine + 1,7-methyluric acid (ratio 2) molar ratios. In group A, all children were slow acetylators before 83 d of age (ratio 1 less than 0.4; ratio 2 less than 0.08), whereas older children included slow and fast acetylators. The acetylation molar ratios differed significantly between age groups and increased with age. The cumulative percentage of fast acetylators increased with age but the plateau was not yet reached at 15 mo. In three children, the phenotyping was repeated after 15 mo: the second determination was consistent with the first one. In group B, all children appeared as slow acetylators on the first phenotyping. Four of them appeared subsequently as fast acetylators; one remained a slow acetylator until 11 mo.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1896254 TI - Postnatal mice have low susceptibility to paracetamol toxicity. AB - The hepatotoxicity of paracetamol in mice of 2, 3, 8-10, 24-26, 32-34, and 52-54 wk of age was determined by lethality data, histopathologic examination of the liver, and appearance of glutamate-pyruvate transaminase and glutamate oxaloacetate transaminase activities in the plasma over an 8-h exposure period. At a dose of 300 mg/kg, there was evidence of hepatocytic necrosis and transaminase leakage in the 32- to 34- and 52- to 54-wk-old mice, but lethality was only recorded in the oldest age group. At 500 mg/kg, paracetamol produced 30% lethality in 3-wk-old mice and between 50 and 90% lethality in the adult age groups. There was histologic evidence of hepatocytic necrosis at all of these ages and its extent increased with age. Similarly, there were increases in plasma transaminases in each of these age groups. However, in 2-wk-old mice there was no lethality, no hepatocytic necrosis, and no increase in plasma transaminases. The lack of susceptibility of 2-wk-old mice to paracetamol toxicity was not due to immaturity of the cytochrome P-450 enzymes responsible for metabolism of paracetamol to its reactive metabolite (N-acetyl-p-benzoquinone imine). In fact, the activity of this enzyme pathway in 2-wk-old mice was greater than that in adults. The partial clearance of the glutathione-derived metabolites of paracetamol after a nontoxic (50 mg/kg) dose was 80% greater in 2-wk-old mice than in 8- to 10-wk-old mice.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1896255 TI - Pharmacokinetics and pharmacodynamics of nifedipine in children with bronchopulmonary dysplasia and pulmonary hypertension. AB - The pharmacokinetics and associated pharmacodynamics of nifedipine were studied in nine children aged 5 to 68 mo with bronchopulmonary dysplasia and pulmonary artery hypertension after a single oral dose of 1.44 mumol/kg (0.5 mg/kg). In the cardiac catheterization laboratory, hemodynamic measurements were made in duplicate just before the nifedipine dose and at 5 min and 0.5 and 1.0 h after the dose. The plasma nifedipine concentration was measured by HPLC at each of the above times and at 2.5, 4.0, 6.0, and 8.0 h after the dose. The mean (+/- SD) maximum plasma concentration and the time to maximum plasma concentration were 243.4 +/- 194.5 nmol/L and 1.0 +/- 0.8 h, respectively. The mean area under the plasma concentration-time curve was 761 +/- 509 nmol.h/L. The mean elimination rate constant and t1/2 were 0.456 +/- 0.194 h-1 and 1.8 +/- 0.8 h, respectively. Nifedipine caused a significant (p less than or equal to 0.05) reduction in the mean pulmonary artery pressure by 5 min and in the mean pulmonary vascular resistance index and mean aortic pressure by 30 min, and these reductions remained significant through the 1-h measurement interval. The magnitude of acute hemodynamic response correlated closely with the plasma nifedipine concentrations. No significant change occurred in the mean arterial oxygen saturation or cardiac index during the study period. The percentage changes from baseline in the mean pulmonary artery pressure and mean pulmonary vascular resistance index were approximately double the percentage change in the mean aortic pressure, suggesting that nifedipine had some degree of selective impact on the pulmonary vascular bed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1896256 TI - Modulation of neonatal myelopoiesis in newborn rats after 7 days' administration of either granulocyte-monocyte colony stimulating factor or interleukin-3. AB - Single-pulse administration of either recombinant human granulocyte-monocyte colony stimulating factor or recombinant human granulocyte colony stimulating factor to newborn rats has previously been demonstrated to increase the peripheral neutrophil count and modulate bone marrow (BM) neutrophil pools. In our present study, we investigated the effects of 7 d of either recombinant murine granulocyte-monocyte colony stimulating factor (rmGM-CSF) (75 micrograms/kg/d) or recombinant murine IL-3 (rm IL-3) (10 micrograms/kg/d) on newborn rat myelopoiesis. Sprague Dawley newborn rats (greater than or equal to 24 h) were injected (intraperitoneally) daily for 7 d with either rmGM-CSF, rmIL 3, or PBS/BSA. rmGM-CSF induced a significant increase in the peripheral neutrophil count on d 3 (p less than 0.03) and d 7 (p less than 0.001) (75% increase). Additionally, rmGM-CSF induced a 50% increase in the BM neutrophil storage pool (p less than 0.025). rmIL-3 increased the BM colony forming unit granulocyte monocyte pool (p less than 0.001); however, it failed to increase the peripheral neutrophil count or BM neutrophil storage pool. Neither CSF increased the BM neutrophil proliferative pool or BM colony forming unit-granulocyte monocyte proliferative rate. Additionally, 7 d of rmGM-CSF with or without antibiotics did not synergistically alter the mortality rate after group B streptococcol inoculation. This study suggests that rmIL-3 appears to stimulate more neonatal myeloid committed progenitor cell activity compared with rmGM-CSF. Optimal modulation of neonatal myelopoiesis may require the use of a sequential combination of hematopoietic CSF, namely an early-acting CSF followed by a more lineage myeloid-specific CSF. PMID- 1896257 TI - Local cerebral blood flow in the newborn rabbit: an autoradiographic study of changes during development. AB - Cerebral ischemia in the neonate is an important cause of hypoxic-ischemic encephalopathy. Thus, it is important to have an economical and readily available animal model in which to study the local control of the cerebral circulation in the perinatal period. This study demonstrates that the newborn rabbit, a rather immature species at birth, is a suitable neonatal model in which to measure local cerebral blood flow with quantitative iodo[14C]antipyrine autoradiography. One or 2 d after birth, local cerebral blood flow in the newborn rabbit is low, but flow varies distinctly between regions [e.g. 8.9 +/- 1.5 mL.kg-1.s-1 (53 mL.100 g 1.min-1) in the nucleus tractus solitarius and 3.4 +/- 0.7 mL.kg-1.s-1 (20 mL.100 g-1.min-1) in the frontal cortex]. During early postnatal development (i.e between 1 and 8 d), local cerebral blood flow does not change greatly. However, by 17 d, 22 of 26 brain regions exhibit significant marked increases (200-350%) in local cerebral blood flow when compared with blood flow in the newborn. Between 17 and 40 d postnatally, cerebral blood flow continues to increase in 16 of 26 regions (e.g. thalamic areas). In four of the cerebral cortical areas, elevations in flow continue during the period between 40 d of age and adulthood. In contrast to the generalized increases in flow occurring postnatally, a few brain regions (i.e. within the pons and medulla) exhibit only minor changes in cerebral blood flow. The differential pattern and lower basal levels of cerebral blood flow in the neonate compared with the adult may be important determinants in regional susceptibility of the brain to ischemia. PMID- 1896258 TI - Studies of the function and structure of in vitro propagated human granulocytes. AB - In our study, hematopoietic progenitor cells isolated from human umbilical cord blood were grown in an in vitro liquid culture system using the recombinant colony stimulating factors IL-3 plus granulocyte-macrophage colony-stimulatory factor (GM-CSF) or IL-3 plus granulocyte colony stimulating factor (G-CSF). The morphology and function of the cells produced were then studied, and it was demonstrated that continuous exposure to IL-3 plus GM-CSF produced predominantly eosinophilic granulocytes, whereas IL-3 plus G-CSF produced neutrophilic granulocytes. Cells from IL-3/GM-CSF cultures showed progressively increasing oxygen metabolism and locomotive capabilities over time, which became equivalent to peripheral blood neutrophils at wk 4 and 3, respectively. Phagocytic activity of these cells was poor. IL-3/G-CSF cultures produced cells with progressive increases in oxygen metabolism, locomotion, and phagocytosis. These functions never became equivalent to those of peripheral blood neutrophils. Flow cytometric analysis of IL-3/G grown cells showed that they expressed CD11b on their surfaces and that surface expression increased 2-fold after secondary granule secretagogue exposure. Ultrastructurally, the eosinophilic granulocyte nature of the IL-3/GM grown cells was confirmed by immunogold-lectin staining and IL-3/G grown cells were shown to contain antigenic myeloperoxidase. The data demonstrate that human umbilical cord blood mononuclear cells can be used to propagate granulocytes in vitro, that the types of granulocytes produced in this culture system depend on the growth factors used, that the cells produced in vitro develop several of the functional characteristics of peripheral blood granulocytes, and that ultrastructural details of developing human granulocytes can be carefully examined in this model system. PMID- 1896259 TI - Altered organ growth and zinc and copper distribution in endotoxin-treated neonatal mice. AB - Organ weights and the distribution of zinc and copper were compared in HLA/ICR mice that received intraperitoneal injections of 10 micrograms of Serratia marcescens lipopolysaccharide W or of sterile physiologic saline at 2 d of age. Between 5 and 28 d of age, body weight gains were similar in both groups. At 5 and 7 d of age, lipopolysaccharide W-treated mice had significantly lower thymus weights (p less than 0.01). At 7 d of age, liver weight was significantly increased (p less than 0.01) in lipopolysaccharide W-treated mice. Compared with tissue copper concentration in coeval saline-treated mice, lipopolysaccharide W treatment significantly increased copper concentration in thymus at 5 d of age (p less than 0.05) and significantly decreased concentration of this metal in liver at 7 d of age (p less than 0.05) and in spleen at 14 d of age (p less than 0.05). Liver zinc concentration was significantly lower (p less than 0.05) in 28-d-old mice that had received lipopolysaccharide W. When expressed on the basis of total organ burdens of zinc or copper, only the liver burden of zinc in 5-d-old lipopolysaccharide W-treated mice was significantly increased (p less than 0.05). Lipopolysaccharide W treatment consistently decreased copper concentration in liver cytosol and the amounts of zinc and copper bound to metallothionein, a transition metal-binding protein, in liver cytosol. These effects of lipopolysaccharide W on organ size and metal distribution may contribute to the adverse effects that persist after endotoxin exposure in early life. PMID- 1896260 TI - Insulin-like growth factor I in substrate-deprived, growth-retarded fetal rats. AB - Plasma, amniotic fluid, and tissue concentrations of IGF-I were examined in nutritionally deprived, growth-retarded fetal rats to determine whether IGF-I concentration serves as a marker for nutritional status. Growth retardation was induced by 72 h of maternal fasting. Twenty-three control and 17 growth-retarded fetuses were individually analyzed and compared. Plasma IGF-I concentrations were significantly lower in test compared with control animals (test 56.8 +/- 14.9, control 87.4 +/- 17.5 ng/mL, p less than 0.01). Amniotic fluid IGF-I concentrations were not different (test 14.0 +/- 8.7, control 12.2 +/- 2.6 ng/mL). IGF-I concentrations obtained from both placental and hepatic tissues were lower in test compared with control animals [placenta: test 293 +/- 25 versus control 655 +/- 114 ng/g (p less than 0.001); hepatic: test 173 +/- 38 versus control 230 +/- 51 ng/g (p less than 0.01)]. Reductions in fetal, placental, and hepatic weights in test animals were more closely related to changes in placental IGF-I concentration than to either plasma or hepatic IGF-I concentrations. We conclude that fetal plasma IGF-I is a valuable marker for intrauterine substrate deprivation and that the growth-retarded rat fetus is accurately identified and specifically characterized by a low placental concentration of extractable IGF-I. PMID- 1896261 TI - Effect of birth-related events on metabolism in fetal sheep. AB - At birth, changes in utilization of metabolic substrates occur as the fetus, dependent upon carbohydrates and amino acids available continuously from the placenta, becomes a neonate, dependent primarily upon fat obtained intermittently by suckling. In addition to changes in substrates, at birth, metabolic rate increases dramatically as the activity of several organs and thermoregulatory mechanisms increase. To determine whether metabolic changes are related to certain events that occur at birth, we studied 15 fetal sheep instrumented chronically with vascular catheters and an endotracheal tube at 133 to 137 d gestational age. We measured blood flow with radionuclide-labeled microspheres and arteriovenous concentration differences for oxygen content, blood glucose, and lactate across the placental, cerebral, myocardial, and hindlimb circulations at rest, during in utero ventilation of the fetal lungs with 3% O2, during in utero ventilation with 100% O2, and during ventilation with 100% O2 and umbilical cord occlusion. Ventilation with 3% O2 decreased oxygen uptake by the fetus and by the cerebral circulation but produced no other significant changes. Ventilation with the low and high oxygen gas mixture reduced glucose uptake by the fetus from the placental circulation dramatically to zero. In contrast, blood glucose concentrations increased and glucose uptake by the fetal brain, heart, and hindlimb were not altered significantly. These data indicate that, for a short time at least, complete cessation of glucose supply to the fetus from the placenta is not associated with decreases in blood glucose concentrations or utilization of glucose by a major portion of the fetal body. PMID- 1896262 TI - Developmental changes in tracheal structure. AB - Mechanical properties of the proximal airways are known to change with development; the highly compliant airways of the immature animal become stiffer and less collapsible with increasing age. Although the relationship between tracheobronchial architecture and function has been described for adult physiology, little is known regarding this relationship during early development. This study was, therefore, designed to test the hypothesis that alterations in tracheal morphometry parallel developmental differences in tracheal functional properties. Tracheal segments obtained from 29 lambs ranging in age from 70% of gestation to full-term newborn lambs up to 6 d old were examined using anatomic, morphometric, and histochemical techniques. The results showed 1) progressive increases in the dimensions of the trachea and the tracheal wall components, 2) alterations in the geometric arrangement of the tracheal ring, and 3) changes in the compositional characteristics of the tracheal cartilage with maturation. These findings demonstrate alterations in tracheal architecture, each of which contribute to the greater stiffness of the trachea, in older animals. When considered together, these factors help explain the differences in tracheal functional characteristics with development. PMID- 1896263 TI - Endothelium-dependent relaxations of piglet pulmonary arteries augment with maturation. AB - To determine whether maturation alters endothelium-dependent responses in porcine pulmonary arteries, rings, with and without endothelium, of small pulmonary arteries taken from piglets of 3, 10, and 30 d of age were suspended in organ chambers filled with buffered salt solution, bubbled with 95% O2-5% CO2, and maintained at 37 degrees C. These studies were performed in the presence of indomethacin (10(-5) M) to inhibit prostaglandin synthesis. In rings without endothelium, potassium chloride (10(-2) to 8.5 x 10(-2) M) and histamine (10(-9) to 10(-5) M) caused concentration-dependent contractions. When normalized to maximal contractions achieved to each agonist, the concentration-effect curves to potassium chloride and histamine in rings without endothelium were similar at each age. Rings with endothelium showed a progressive shift to the right of the concentration-effect curve to histamine, possibly secondary to an increase in the basal release of, or responsiveness to, the endothelium-derived relaxing factor with maturation. Relaxations to sodium nitroprusside (10(-9) to 10(-5) M) were unaffected by age. In precontracted rings, acetylcholine (10(-9) to 10(-6) M), bradykinin (10(-10) to 10(-6) M), and the calcium ionophore A23187 (10(-9) to 10( 6) M) caused relaxations in rings with endothelium, but not in those without endothelium, which were greater at 10 and 30 d compared to 3 d; further augmentation at 30 d compared to 10 d was not observed. In rings without endothelium, changes in the responsiveness to nitric oxide (10(-9) to 10(-5) M), one of the proposed endothelium-derived relaxing factors, with age were comparable to those observed with endothelium-dependent relaxing agents. These studies demonstrate that endothelium-dependent relaxations increase with age, possibly due to changes in sensitivity of the smooth muscle to the endothelium derived relaxing factor. PMID- 1896265 TI - Lanthanum inhibits surfactant secretion stimulated by lung distension in newborn rabbits. AB - The effect of lanthanum on lung phospholipid secretion stimulated by lung distension was examined in 29.5-d gestation newborn rabbits. Lung lavage with saline alone produced 608 +/- 109 micrograms phospholipid/lung (mean +/- SEM), whereas lavage with 10(-3) M lanthanum produced only 153 +/- 40 micrograms phospholipid/lung (p less than 0.05), the difference in yield being attributed to inhibited lavage-induced secretion with lanthanum. If this interpretation is correct, then an increased residual tissue surfactant should be found in lanthanum-lavaged lungs. Postlavaged lung was separated into IA, IB, and IC fractions by homogenization and then centrifugation with 0.25 and 0.65 M sucrose. The surfactant IB fraction was 763 +/- 65 micrograms phospholipid/g wet lung for saline-lavaged lungs, but 1002 +/- 90 micrograms phospholipid/g wet lung for lanthanum-lavaged lungs (p less than 0.002). This confirms that decreased secretion with lanthanum was associated with increased residual surfactant in postlavaged lung. It is concluded that lanthanum is a potent inhibitor of surfactant secretion stimulated by lung distension. PMID- 1896264 TI - Surfactant improves gas mixing and alveolar ventilation in preterm lambs. AB - Prophylactic treatment with ovine surfactant was evaluated in preterm lambs at risk for development of hyaline membrane disease. Eight mechanically ventilated newborn lambs were treated before delivery and 10 served as controls (gestational age 129-131 d). Lung mechanics, functional residual capacity, alveolar ventilation, efficiency of ventilation, and distribution of ventilation were tested using pressure, flow, and nitrogen elimination (nitrogen washout during 100% oxygen breathing) measurements in the endotracheal tube. The surfactant treated animals showed significantly improved gas mixing efficiency in the lung with improved alveolar ventilation. Single exponential washout pattern dominated in both groups. Adequate functional residual capacity was established earlier after birth in the treated lambs than in the control animals. Lung mechanics in the treated group showed significant improvement in dynamic lung compliance. Surfactant treatment also improved gas exchange and reduced respirator pressure requirement. We speculate that the main functional effect of surfactant treatment in preterm lambs at risk to develop hyaline membrane disease is to maintain the patency of the peripheral airways in the lung, which improves diffusive gas mixing, alveolar ventilation, and gas exchange. The techniques used in this study should also be useful to evaluate lung function in preterm human infants after specific adaptation of the equipment size. PMID- 1896266 TI - The effects of lung distension, oxygenation, and gestational age on fetal behavior and breathing movements in sheep. AB - Lung distension with 100% O2 at a continuous positive airway pressure of 30 cm H2O may induce continuous fetal breathing movements (FBM) in sheep. The objectives of this study were 1) to investigate the relative roles of lung distension and oxygenation and 2) to test the hypothesis that FBM can be induced during labor, when normally they are greatly reduced or absent. We studied 13 chronically instrumented, unanesthetized fetal sheep between 128 and 144 d of gestation (term = 147 +/- 2 d). Each fetus was instrumented to record sleep states, diaphragm electromyogram, blood pressure, arterial pH, and blood gas tensions. The fetal lungs were distended via an in situ endotracheal tube with four different concentrations of O2 (0, 21, 50 and 100%) at a continuous positive airway pressure of 10, 20 and 30 cm H2O in a randomized order. No change in any recorded physiologic variable was observed at 129 +/- 1 or 132 +/- 1 d of gestation. At 135 +/- 1 and 138 +/- 1 d, in response to a continuous positive airway pressure of 30 cm H2O and 100% O2, pH decreased (p = 0.0004 and 0.005, respectively) and arterial O2 tension increased (p = 0.004 and 0.02, respectively). However, increases in 1) breathing time, 2) breathing time/low voltage electrocortical activity ratio, 3) duration of arousal, and 4) length of single breathing epochs were observed only at 138 +/- 1 d. Lung distension with N2 resulted in a decrease in FBM. Six fetuses were studied during labor.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1896267 TI - Contractile response to sympathetic innervation in neonatal ventricular cardiomyocytes of the spontaneously hypertensive rat. AB - Differences in cardiac development between spontaneously hypertensive rats (SHR) and their normotensive Wistar Kyoto (WKY) controls are observed before the onset of hypertension. To determine whether intrinsic differences in myocardium or autonomic neurons might be responsible for these observations, we studied primary cultures of isolated, never previously innervated ventricular cardiomyocytes from neonatal rats of both strains, and sympathetic innervation was produced by addition of neurons from thoracolumbar sympathetic ganglia. Both same-strain and cross-strain innervation were compared. Amplitude and frequency of contraction were measured from video images of spontaneously contracting cells by on-line video motion analysis. Sympathetic innervation improved contractile function by 61% in SHR cardiomyocytes (p less than 0.001), an effect qualitatively similar to that previously reported for WKY cardiomyocytes. Contractile function of SHR cardiomyocytes cultured without sympathetic explants was 25% less than that of WKY cells (p less than 0.005), but the response of SHR cardiomyocytes to sympathetic innervation was twice as great as that of WKY myocytes (p less than 0.01). Cross-strain innervation experiments showed that sympathetic neurons from both strains were equally effective; interstrain differences were confined to the cardiomyocytes. Interstrain differences in cardiomyocyte contractile function and contractile response to sympathetic innervation are present before the onset of hypertension, and may in part account for alterations in cardiac function observed in prehypertensive SHR. PMID- 1896268 TI - A controlled clinical trial of local anesthesia for lumbar punctures in newborns. AB - To evaluate the efficacy of subcutaneous administration of lidocaine for reducing physiologic instability in acutely ill newborns during clinically required procedures, 81 neonates who required lumbar punctures within the first month of life were stratified by birth weight and respiratory support and randomly assigned to an experimental or a control group. The experimental group received an injection of 0.1 mL/kg of 1% lidocaine prior to the lumbar puncture. The control group received a nonanesthetized lumbar puncture without placebo. Changes in heart rate, respiratory rate, transcutaneous oxygen and carbon dioxide tensions, and heart rate variability from baseline, preparatory (positioning/handling), lumbar puncture, and recovery periods were measured. The administration of lidocaine did not minimize physiologic instability in response to the lumbar puncture nor was it associated with any detectable adverse effects other than prolonging the duration of the lumbar puncture. Although significant physiologic changes were observed in response to preparatory procedures, few additional changes beyond those occurred in response to lumbar punctures in either the experimental or control group. It is concluded that local anesthesia failed to influence manifestations of physiologic instability during neonatal lumbar punctures and that preparatory procedures were more destabilizing than either the administration of lidocaine or the lumbar puncture itself. The results suggest that the management of newborns requires emphasis on minimizing the destabilizing effects of required and frequent handling procedures. PMID- 1896269 TI - Prior approval in the pediatric emergency room. AB - Managed-care plans for low-income Americans are widely promoted to improve the quality and control the cost of medical care by reducing unnecessary specialty and emergency room (ER) care through the use of primary care physicians as case managers/gatekeepers. The purpose of this study was to evaluate one element of managed care, gatekeeping prior approval, for children who use the pediatric ER of one urban public hospital. Over a 6-month period, 518 children and adolescents insured under managed-care plans that required authorization from the primary care physician to receive treatment presented to the ER. Of the 385 records reviewed for this study, the majority (87%) received their primary care at community health centers or the hospital's own outpatient clinics. Most ER visits (72%) were made when primary care sites were closed. According to nursing triage assessment, 57% presented with urgent or emergent conditions, and 26% had a history of chronic illness. Nine percent required hospitalization. Although an elaborate system for gatekeeping was established, only 13 (3%) patients' requests for ER care were denied. Of these, 3 were seen in the ER without authorization, 6 received the recommended follow-up, and 4 were not seen in follow-up. Twenty-nine participating primary care physicians (74%) and 19 ER staff (63%) responded to a survey of their experience with and attitudes toward prior approval. For a variety of reasons, the majority of primary care physicians and ER staff found the gatekeeping policies for after-hours visits burdensome and inappropriate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1896271 TI - Pediatric emergency transport and the private practitioner. AB - A mail survey of 182 pediatricians and 92 family practitioners in Pennsylvania was conducted to determine their methods of transport of seriously ill children from their offices to referral centers and their involvement with professional transport services. Although most physicians (93.1%) stated that they had professional services available to them (at their office location), more than half (53.8%) indicated that the patient's family automobile was their most commonly used method of transport of ill children to tertiary care centers. This was true regardless of the disease entity involved, including suspected epiglottitis. Practice setting had little influence on transport method. However, in general, younger children were judged to need ambulance transport more often than older children. Reasons cited for not using professional transport from the office included a perceived better efficiency of the family car (61.8%), the prohibitively high expense of professional transport (9.8%), and failure to consider professional transport (6.5%). Further study of this component of office preparedness is suggested. PMID- 1896270 TI - Pediatric prehospital care in urban and rural areas. AB - There are limited data concerning pediatric prehospital care, although pediatric prehospital calls constitute 10% of emergency medical services activity. Data from 10,493 prehospital care reports in 11 counties of California (four emergency medical services systems in rural and urban areas) were collected and analyzed. Comparison of urban and rural data found few significant differences in parameters analyzed. Use of the emergency medical services system by pediatric patients increased with age, but 12.5% of all calls were for children younger than 2 years. Calls for medical problems were most common for patients younger than 5 years of age; trauma was a more common complaint in rural areas (64%, P = .0001). Frequency of vital sign assessment differed by region, as did hospital contact (P less than .0001). Complete assessment of young pediatric patients, with a full set of vital signs and neurologic assessment, was rarely performed. Advanced life support providers were often on the scene, but advanced life support treatments and procedures were infrequently used. This study suggests the need for additional data on which to base emergency medical services system design and some directions for education of prehospital care providers. PMID- 1896272 TI - Pediatric interhospital critical care transport: consensus of a national leadership conference. AB - As pediatric interhospital critical care transport has evolved toward a distinct discipline, practitioners in this field have recognized the need for guidelines for transport program development and patient care. At a gathering of medical directors of pediatric transport programs, the following topics were discussed: team composition and transport staffing, training requirements for pediatric and nonpediatric transport teams, goals and design of a transport data base, and medical-legal issues, including the responsibilities of the referring and receiving institutions. Consensus recommendations were made for the major issues in each of these areas. Several questions were raised which may be answered by multiinstitutional studies. PMID- 1896273 TI - Child care options for ill children. AB - Care of ill children who normally attend out-of-home child care programs poses a problem for many working parents, employers, and child care workers. Children cared for in child care centers have an increased incidence of illness and consequently their parents miss work more often compared with children cared for in other child care arrangements. Programs for the care of ill children are discussed to provide the practicing pediatrician with an understanding of the various programs currently or potentially available in the community. The paper ends with a discussion of the various solutions to enhance the economic gains of working parents while serving the need of children for nurturant care. PMID- 1896274 TI - Recent declines in breast-feeding in the United States, 1984 through 1989. AB - Ongoing surveys performed by Ross Laboratories demonstrate recent declines both in the initiation of breast-feeding and continued breast-feeding at 6 months of age. Comparing rates in 1984 and 1989, the initiation of breast-feeding declined approximately 13% (from 59.7% to 52.2%), and there was a 24% decline in the rate of breast-feeding at 6 months of age (from 23.8% to 18.1%). The decline in breast feeding was seen across all groups studied but was greater in some groups than in others. Logistic regression analysis indicates that white ethnicity, some college education, increased maternal age, and having an infant of normal birth weight were all positively associated with the likelihood of both initiating breast feeding and continuing to breast-feed to at least 6 months of age. Women who were black and who were younger, no more than high school educated, enrolled in the Women, Infants and Children supplemental food program, working outside the home, not living in the western states, and who had an infant of low birth weight were less likely either to initiate breast-feeding or to be nursing when their children were 6 months of age. The factors influencing the decline in breast feeding were not uniform. There were fewer sociodemographic factors associated with the decline in the initiation of breast-feeding than in the decline in prolonged breast-feeding. While the disparity between older and younger mothers in initiating breast-feeding increased, there was an offsetting trend as the disparity associated with parity decreased.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1896275 TI - Incidence and correlates of breast-feeding in socioeconomically disadvantaged women. AB - Although the incidence of breast-feeding has more than doubled in the United States in recent years, this increase has been less evident among blacks and in lower socioeconomic groups. To understand better this lower incidence, cognitive and personality correlates of breast-feeding were examined in two independent lower-class samples: 137 black inner-city mothers and 50 predominantly white mothers. Ego development, depression, and verbal competence were assessed during the first postpartum year. Only 21.9% of the black sample chose to breast-feed, in contrast with 58.0% of the white sample. Although unrelated to depression and social support, breast-feeding was positively associated with ego level and cognitive ability in both samples. Cognitive ability was assessed using the Peabody Picture Vocabulary Test-Revised, which was found to be valid in relation to maternal and infant characteristics for the black socially disadvantaged sample. When compared using multiple regression analysis, the relation of ego maturity to breast-feeding was generally stronger than that of cognitive ability. Women with more ego maturity may breast-feed because of increased feelings of empathy or nurturance or because they are more attuned to current health advisories and able to deviate from community norms to adopt breast-feeding practices more characteristic of the white middle class. PMID- 1896276 TI - Maternal diet alters the sensory qualities of human milk and the nursling's behavior. AB - Although the majority of human infants are breast-fed for the first few months of life, there is a paucity of information regarding the sensory qualities of human milk and how these qualities are affected by maternal diet. The present study investigated the effects of garlic ingestion by the mother on the odor of her breast milk and the suckling behavior of her infant. Evaluation of the milk samples by a sensory panel revealed garlic ingestion significantly and consistently increased the perceived intensity of the milk odor; this increase in odor intensity was not apparent 1 hour after ingestion, peaked in strength 2 hours after ingestion, and decreased thereafter. That the nursling detected these changes in mother's milk is suggested by the finding that infants were attached to the breast for longer periods of time and sucked more when the milk smelled like garlic. There was a tendency for infants to ingest more milk as well; the lack of a significant effect may be due to the inherent limitations on the total amount of milk available to the infant. PMID- 1896277 TI - Early formula supplementation of breast-feeding. AB - Factors influencing early formula supplementation in breast-fed neonates were examined among 726 women who were delivered of their first child in one of three metropolitan Washington, DC, hospitals. Thirty-seven percent of breast-fed neonates were given supplementary formula in the hospital. Mothers who gave birth at a university hospital were more likely to breast-feed exclusively (adjusted odds ratio 3.5; 95% confidence limit 2.1 to 5.9), after adjustment for maternal demographics, hospital factors (such as time of first breast-feed, demand feeding, delivery type, and rooming-in), and the maternal breast-feeding commitment. Aside from delivery hospital, a strong predictor of formula use was the time between birth and initiation of the first breast-feed. The longer a mother waited to initiate breast-feeding the more likely she was to use formula; the adjusted odds ratios for women who initiated breast-feeding 2 to 6 hours, 7 to 11 hours, and 12 or more hours postpartum were 1.1, 0.5, and 0.2, respectively. Feeding the baby on demand, having a vaginal delivery, deciding to breast-feed before pregnancy, having a college education, and being married also were moderately, though significantly, predictive of exclusive breast-feeding. The findings suggest that hospital influences can promote formula use and indirectly shorten breast-feeding duration, particularly those hospital practices that delay early initiation of breast-feeding. PMID- 1896278 TI - Vitamin K status of lactating mothers, human milk, and breast-feeding infants. AB - Hemorrhagic disease of the newborn is a disease of breast-feeding newborns. There is little information on longitudinal breast milk concentrations of phylloquinone (vitamin K1) or the effects of maternal phylloquinone supplements on breast milk. In study part 1, 11 lactating mothers, who received 20 mg of phylloquinone orally, had rises in plasma (less than 1 to 64.2 +/- 31.5 ng/mL by 6 hours) and breast milk concentrations (from 1.11 +/- 0.82 to 130 +/- 188 ng/mL by 12 hours). In part 2, 23 lactating mothers and their infants were observed longitudinally along with a formula-fed control group of infants (n = 11). Mean breast milk concentrations of phylloquinone at 1, 6, 12, and 26 weeks were 0.64 +/- 0.43, 0.86 +/- 0.52, 1.14 +/- 0.72, and 0.87 +/- 0.50 ng/mL, respectively, in the infants fed human milk. Maternal phylloquinone intakes (72-hour dietary recalls) exceeded the recommended daily allowance of 1 microgram/kg per day. Infant phylloquinone intakes did not achieve the recommended daily allowance of 1 microgram/kg per day in any infant. Plasma phylloquinone concentrations in the infants fed human milk remained extremely low (mean less than 0.25 ng/mL) throughout the first 6 months of life compared with the formula-fed infants (4.39 to 5.99 ng/mL). In this small sample, no infant demonstrated overt vitamin K deficiency. Despite very low plasma phylloquinone concentrations, vitamin K supplements (other than in the immediate newborn period) cannot be recommended for exclusively breast-fed infants based on these data. PMID- 1896279 TI - Perceptions of vulnerability 3 1/2 years after problems of feeding and crying behavior in early infancy. AB - The long-term consequences for infants with problems of feeding and crying behavior remain unknown. The purpose of this research was to determine whether such children are later perceived by their parents as vulnerable and more often have behavior problems and have different personalities than children without problems in infancy. The implications of managing such problems by changing milk formulas is explored. Mothers of 379 infants were enrolled in the postpartum period. Information about problems of feeding and crying behavior was obtained at 4 months. Thirty-six percent of the infants had problems and the formula had been changed for 17%. At 3 1/2 years, 320 (84%) mothers completed a questionnaire. Children who had had problems were more often perceived as vulnerable (relative risk [RR] 1.86; 95% confidence interval [CI] 1.09, 3.19) and more often had behavior problems (RR 1.78; 95% CI 1.03, 3.07). There were no differences in personality. Children whose problems had been managed by changing milk formulas were more often perceived as vulnerable (RR 2.18; 95% CI 1.05, 4.53). Although allergies were reported significantly more often for those children who had had problems, there were no differences in the prevalence of asthma or eczema. Problems of feeding and crying behavior in early infancy and the way they are managed may have long-term implications for the child. PMID- 1896280 TI - Pediatrician's practice choices: differences between part-time and full-time practice. AB - A national survey was used to study the differences in career and family patterns of pediatricians who work part-time (PT) vs those who work full-time (FT). A questionnaire mailed to 375 members of the American Academy of Pediatrics asked about age, marital status, number of children, type of practice, hours worked in particular duties, and attitudes about their choices. Sixty-five percent (n = 216) of the questionnaires were completed. The mean age of both the PT and FT women was 40 years, and FT men averaged 46 years. Thirty-seven percent of women had worked PT at some point in their careers; 21% were currently working PT. Only 70% of the FT women were married compared with 97% and 95% of PT women and FT men. The FT women had significantly fewer children (mean 1.27, compared with 2.34 for PT women and 2.39 for FT men). Part-time women in academic medicine tended to do little research or administrative work, but they had more teaching responsibilities. Almost all the PT women were happy with their decisions and careers despite the feeling among many that they had made career compromises. Many of the FT pediatricians wanted to work less. It is concluded that many women, particularly those with children, choose PT work in order to combine career and family duties. These choices may lead to different career paths for women pediatricians. By recognizing these different career paths, it may be possible for academic institutions to benefit from the unique contributions that PT women pediatricians can make. PMID- 1896281 TI - Prevention of pedestrian injuries to children: effectiveness of a school training program. AB - Pedestrian injuries are a complex problem for which no single intervention will be completely effective. One component of a community-wide program, training of schoolchildren in street-crossing skills, is evaluated. The program targeted public school students in grades K through 4 with an eight-session training program by a single teacher, cross-age teaching, videotape feedback, and in 1990 parent-child activity workbooks. Children's street crossing was observed pretraining and posttraining and graded on four behaviors: WALKING on sidewalk/shoulder vs in the street; STOPPING at the curb; LOOKING L-R-L before crossing; KEEP LOOKING while crossing. Analysis was conducted on matched pairs in which observations pretraining were compared with those posttraining on same child. Observations were completed on 137 children in 1989 and 92 in 1990. Nearly all children walked on the side of the road; however, fewer than 50% of children STOPPED, 25% LOOKED, and fewer than 20% KEPT LOOKING before training. Training did not improve the performance on the first two behaviors in either year, significantly increased LOOKING in 1990, and increased KEEP LOOKING by twofold in 1989 and threefold in 1990. It is concluded that pedestrian skills of children can be improved but that such a program must be part of a broader effort if pedestrian injuries are to decrease. PMID- 1896283 TI - Injuries to children and adolescents: impact on physical health. AB - Disability resulting from injuries was examined in a health maintenance organization population of children and adolescents 0 through 19 years of age. The physical health status instrument from the Rand Health Insurance Study was used to evaluate functional outcome of patients seen in the emergency room and outpatient clinic. Overall, 55.1% of individuals had limitations in their usual activities during the week following injury; 16.4% and 3.8% were not yet back to full activities after 1 week and 1 month, respectively. Individuals 10 years of age and older had more functional impairment than did younger children. Restrictions were greatest for fractures/dislocations and sprains and for injuries due to sports, play/recreational activities, and falls. PMID- 1896282 TI - Pedestrian injuries to children younger than 5 years of age. AB - Historically, research on pediatric pedestrian injuries has analyzed children younger than 5 years of age as a single group. However, in this study, these children were divided into two age groups which were reflective of differences in behavior and development. The data demonstrate differences in the circumstances of the pedestrian injury events between toddlers (0 through 2 years and ambulatory) and preschoolers (3- and 4-year-olds). Toddlers were more likely to be injured in nontraffic events whereas preschoolers were more frequently injured in traffic situations. A high proportion of toddler injuries occurred in residential driveways and were caused by vehicles backing up. The majority of preschoolers, often without supervision, were injured while crossing/darting midblock on residential streets near their homes. Reflecting these differences in circumstances and also developmental differences between toddlers and preschool children, there is a need for age-specific interventions to reduce pedestrian injuries in children younger than 5 years of age. PMID- 1896284 TI - Evaluation of graduating neonatal nurse practitioners. AB - To compare the knowledge and problem-solving, communication, and clinical skills of graduating neonatal nurse practitioners (NNPs) and pediatric residents, a cohort study was conducted in a 33-bed tertiary-level neonatal intensive care unit in a 400-bed teaching hospital affiliated with a faculty of health sciences. Participants were all (n = 10) NNP graduates from the first 3 years of the educational program and 13 (87%) of 15 second-year pediatric residents. One hundred multiple-choice questions and 20 radiographic slides were used to test knowledge; a semistructured oral examination tested problem-solving skills; three simulated interactions with parents tested communication skills; and seven simulated procedures tested clinical skills. Graduating NNPs scored similarly to the pediatric residents on the multiple-choice questions (difference -3.4%; 95% confidence interval [CI] around difference -9.7, 2.9), radiographs (difference 1.4%; 95% CI -11.5, 8.7), oral examination (difference 2.8%; 95% CI -11.1, 16.7), communication skills (simulated parents assessment: difference 0.8%; 95% CI -4.2, 5.7; expert observer assessment: difference 5.8%; 95% CI -2.8, 14.3), and clinical skills (difference 7.4%; 95% CI -5.5, 20.2). The NNPs about to graduate from their educational program showed knowledge and problem-solving, communication, and clinical skills equivalent to those of second-year pediatric residents and are thus likely to deliver comparable care in the clinical setting. The results support the adoption of the NNP role. PMID- 1896285 TI - Visitation to a neonatal intensive care unit. AB - Preterm newborns may experience extended periods of hospitalization which disrupt the normal early contact between the newborn and its family. Variations in the frequency of visits to 164 preterm neonates in a neonatal intensive care unit were examined in relation to infant and family status variables and compliance with follow-up appointments at 3 months postterm. The mean number of visitors decreased from day 2 to day 12 of hospitalization and then remained stable through day 21. There was a corresponding increase in the number of days with no visitors through day 12, and then stabilization. Neonates who had intraventricular hemorrhages, whose parents did not live together, and who were not firstborn had the most days with no visitors. While the mother was hospitalized herself, her condition was the only variable related to percentage of no-visitor days. The sicker the mother, the more likely the newborn had no visitors. The greater the number of days with no visitors, the poorer the likelihood that the infant was brought to a 3-month follow-up clinic appointment. PMID- 1896287 TI - Small bowel evisceration: unusual manifestation of child abuse. PMID- 1896286 TI - Starvation ketosis after rehydration with diet soda. PMID- 1896288 TI - Persistent eosinophilia in an infant with probable intrauterine exposure to L tryptophan-containing supplements. PMID- 1896289 TI - Pediatric telephone advice: Seattle hotline experience. PMID- 1896290 TI - Captopril-induced reversible acute renal failure in an infant with coarctation of the aorta. PMID- 1896291 TI - Primary central hyperventilation in a child with a brainstem glioma: management with continuous intravenous fentanyl. PMID- 1896292 TI - Is a chest radiograph necessary in the evaluation of every febrile infant less than 8 weeks of age? AB - This study was designed to examine the relationship between respiratory signs and the likelihood of having an abnormal chest radiograph in a sample of febrile infants less than 8 weeks of age. The sample consisted of 242 infants who were admitted during a 3-year period with temperatures greater than or equal to 38 degrees C (100.4 degrees F) and had a chest radiograph. The house officer recorded the presence of respiratory signs and symptoms including rhinorrhea, tachypnea, cough, rales, wheezes, retractions, and rhonchi. Each chest radiograph was reviewed independently according to predetermined criteria by a senior radiology resident and an attending pediatric radiologist. Interobserver agreement was 91%. Both observers were blind to the infants' respiratory signs. The chest radiograph interpretations were compared with the presence of respiratory signs. Of the 242 cases, 228 had chest radiographs available for interpretation. Of these, 27 chest radiographs (12%) were identified as abnormal, including 6 where there was initial disagreement as to the presence of an abnormality. Twenty-five (31%) of 80 infants with any respiratory signs had an abnormal chest radiograph, whereas only 2 (1%) of 148 asymptomatic infants did. The sensitivity of respiratory signs was 93% (confidence interval = 76% to 99%). These findings suggest that in the absence of respiratory signs, febrile infants are unlikely to have an abnormal chest radiograph. PMID- 1896293 TI - Incidence of intrauterine cocaine exposure in a suburban setting. AB - This study endeavored to determine the incidence of intrauterine cocaine exposure in a socioeconomically mixed suburban setting. It also assessed the effectiveness of an anonymous questionnaire in eliciting information on maternal use of illicit drugs during pregnancy. Meconium was collected from 500 consecutively born infants and analyzed for the presence of cocaine and its metabolites. An anonymous two-page questionnaire also was distributed to all postpartum mothers. Of the infants' mothers, (73.2%) were covered by some form of insurance (private), whereas 26.8% either had no insurance or were covered by Medicaid (clinic). Fifty-nine (11.8%) babies tested positive for cocaine. The meconium of 6.3% of the babies whose mothers had private insurance tested positive, while the meconium of 26.9% of the babies whose mothers had Medicaid or no insurance tested positive. 316 (63.2%) of the mothers returned a questionnaire. 73% had private insurance and 27% were covered by Medicaid (clinic). Only five mothers with no insurance or covered by Medicaid admitted using cocaine. It appears that neonatal exposure to cocaine may be an even greater problem than previously imagined, particularly in the private population. In addition, anonymous maternal self reporting forms probably will not be helpful in identifying infants at risk for illicit exposure to drugs. PMID- 1896294 TI - Neonatal hyperbilirubinemia and physical and cognitive performance at 17 years of age. AB - To estimate the effect of neonatal hyperbilirubinemia on long-term cognitive ability in full-term newborns with a negative Coombs test, we performed a 17-year historical prospective study of 1948 subjects. Intelligence tests and medical examinations performed at the military draft board were stratified according to serum bilirubin concentration. A logistic regression analysis was used to adjust for the confounding effects of gestational age, birth weight, Apgar score, ethnic origin, socioeconomic class, paternal education, birth order, and the administration of phototherapy and exchange transfusion. No direct linear association was shown between neonatal bilirubin levels and intelligence test scores or school achievement at 17 years of age. However, the risk for low intelligence test scores (IQ score less than 85) was found to be significantly higher (P = .014) among full-term male subjects with serum bilirubin levels above 342 mumol/L (20 mg/dL) (odds ratio, 2.96; 95% confidence interval, 1.29-6.79). This association was not observed among female subjects. We conclude that severe neonatal hyperbilirubinemia, among full-term male newborns with a negative Coombs test, could be associated with lower IQ scores at 17 years of age. PMID- 1896295 TI - Gastroesophageal reflux, as measured by 24-hour pH monitoring, in 509 healthy infants screened for risk of sudden infant death syndrome. AB - Continuous long-term esophageal pH monitoring has become the preferred test to quantify acid gastroesophageal reflux. Because reflux to a limited extent is physiologic, the determination of optimal thresholds to separate normal from abnormal reflux is mandatory. Esophageal pH was measured during 24 hours in 509 healthy thriving infants, aged 3 days to 1 year, using a glass microelectrode with an external reference electrode connected to a portable recorder. Percentiles of the four parameters studied (reflux index or percent of the investigation time with a pH less than 4, number of episodes with a pH less than 4 during 24 hours, number of episodes lasting greater than 5 minutes, the duration of the longest episode (in minutes) are presented. A percentile curve of the reflux index regarding the age distribution shows that the normal range for the reflux index during the first 12 months of life is about 10% (95 percentile), decreasing from 13% at birth to 8% at 12 months. Application of an age-related percentile curve offers a close-to-reality possibility of data interpretation and illustrates that there is inevitably an overlap of data between normal and abnormal populations, because reflux is a phenomenon occurring to some extent in every human being. PMID- 1896296 TI - Focal encephalitis with enterovirus infections. AB - We report on four pediatric patients with Enterovirus infections who were admitted to the hospital with signs or symptoms of acute, focal encephalitis. All four experienced focal seizures. Each had a cerebrospinal fluid pleocytosis at the initial lumbar puncture. In all four patients the diagnosis of herpes simplex encephalitis was entertained. Each child improved spontaneously within a few days of admission to the hospital, and only one had residual neurologic abnormalities at the time of discharge. A brief review of these cases, and three additional cases from the literature, indicate that the enteroviruses, particularly the group A Coxsackieviruses, are rare causes of acute focal encephalitis in children and adolescents. PMID- 1896297 TI - Psychosocial influences on acquired immunodeficiency syndrome-risk behaviors among high school students. AB - A survey measuring acquired immunodeficiency syndrome (AIDS)-related behaviors and selected psychosocial factors was administered to 1091 tenth grade students residing in or near an AIDS epicenter. The purpose of the survey was to identify salient risk factors that could be targeted in AIDS prevention programs. By 15 years of age, one quarter of students reported engaging in behaviors that placed them at higher risk for acquiring infection with human immunodeficiency virus, and 3% of students reported engaging in very high-risk behaviors. Students exposed to certain psychosocial stressors (ie, adverse life circumstances and poor parental support), who engaged in other problem behaviors (ie, substance use and academic problems) and who had higher self-esteem, were more likely to engage in higher risk behaviors. Pediatricians and other clinicians, particularly those working in or near AIDS epicenters, who encounter adolescents with multiple psychosocial problems, should be alert to the possibility that these youths also are engaging in behaviors that place them at risk for AIDS. Comprehensive care for these teenagers must include an assessment of involvement in AIDS-risk behaviors and appropriate behavioral counseling. PMID- 1896298 TI - Standards for selected anthropometric measurements in Prader-Willi syndrome. AB - We report standards (95th, 50th, and 5th centiles) in Prader-Willi syndrome for weight, height, sitting height, head circumference, head length, head breadth, hand length, middle finger length, palm length, hand breadth, foot length, foot breadth, triceps skinfold, and subscapular skinfold. For comparison with Prader Willi syndrome standardized curves, normal control data from the literature were plotted similarly and standard curves were produced. We encourage the use of these standards with the examination of patients who have Prader-Willi syndrome and in the comparison of the patient who has Prader-Willi syndrome with other similarly affected individuals. The standards may also be useful for assisting in the diagnosis of Prader-Willi syndrome, particularly in younger individuals. PMID- 1896299 TI - Career plans of new pediatricians: results from a survey of residency program directors. AB - Directors of pediatric residency programs in the United States, Puerto Rico, and Canada were surveyed regarding plans of graduating residents to determine whether new pediatricians experienced problems finding employment in light of a decreasing growth rate in the child population. Nearly 90% of directors responded, providing information on 1915 residents. Of the 1782 nonmilitary residents in the United States, 815 were entering general pediatric practice and one third (596) were entering subspecialty training. Nearly one half (379) of residents entering general pediatric practice were joining a small group practice, almost one fourth (184) were joining a larger group, 6% (48) were becoming solo practitioners, 7% (57) were joining a health maintenance organization, and nearly 8% (62) were joining a hospital or academic staff. Most residents in the United States experienced no difficulty finding a position and received multiple offers for jobs. Canadian residents were similar to residents in the United States, whereas the postresidency situations of graduates of military and Puerto Rican programs were very different. Despite manpower predictions to the contrary, comments by program directors indicated a demand for general pediatricians. This paper presents only the viewpoint of program directors; whether this perceived need illustrates an avid market for young general pediatricians merits further study. PMID- 1896300 TI - Breast-feeding trends: a cause for action. PMID- 1896301 TI - Frogger. PMID- 1896302 TI - What happened to the predicted glut of pediatricians? PMID- 1896303 TI - Decline in breast-feeding? PMID- 1896304 TI - Pedia-what! PMID- 1896305 TI - Arterial catheters, endothelin, and ROP. PMID- 1896306 TI - Causes of encopresis. PMID- 1896307 TI - Should promethazine be available without prescription? PMID- 1896309 TI - The effectiveness initiative: implications for nursing practice and research. PMID- 1896310 TI - Entry: a new approach. AB - Despite all of the protections promised through grandfathering and pathways to educational mobility, the entry movement tends to be perceived by many to be "demoting" the lives and livelihoods of hundreds of thousands of RNs who do not possess the education to meet the proposed standard. Here is a proposal for a way out of the quagmire. PMID- 1896308 TI - Sexually transmitted diseases in childhood sexual abuse. PMID- 1896311 TI - Who counts in news coverage of health care? AB - In a study of the sources of health care news, nurses appeared to be virtually silent: Journalists do not seek out nurses as sources of information on health care. Even female journalists adhere to the same definition of expertise held by their male colleagues and virtually never use nurses as a source of news. PMID- 1896312 TI - Perspectives on role socialization of nurses. AB - Individuals enact roles according to their personal knowledge of the role and the expectations of others interacting with the role. This is especially evident in patient care, where depths of knowledge are crucial to outcomes. The pecking order of health care professionals is directly related to the knowledge levels of the role enactors. Nurses tend to be the proverbial low man on the totem pole. PMID- 1896313 TI - A family caregiving model for public health nursing. AB - The absence of clear definitions of public health nursing competency have plagued efforts to demonstrate the need for public health nursing programs. This article describes a model that can be used to explain why public health nursing services should be integral to the public agenda. PMID- 1896314 TI - Endowed chairs in nursing. AB - Two distinguished scholars discuss aspects of endowed chairs: Joyce Fitzpatrick provides a brief history of the practice and explains how endowed chairs preserve academic freedom and nursing's place in scientific inquiry. M. Elizabeth Carnegie recounts a brief history of endowed chairs in the U.S. and relates her own experiences gained from filling endowed chairs in nursing. PMID- 1896315 TI - From there to here in fifty years. AB - Braving her family's disapproval and facing life alone in a strange city, Dorothy Mereness graduated from nursing school in 1941 at the age of 31. From there she embarked upon a half-century career as an innovative educator and pioneer in the field of psychiatric nursing. Here is an overview of her life in her own words. PMID- 1896316 TI - A national board for nursing certification. AB - As late as 1988, the term "certification" had no consistent meaning within nursing. By 1991, eight organizations representing over 120,000 certified nurses had joined together to establish the American Board of Nursing Specialties, a group dedicated to assuring consistent and rigorous standards for certifying nursing specialties. Here's how it happened. PMID- 1896317 TI - Lydia Holman: community health pioneer. AB - Trained and inspired by the Henry Street Settlement, this Pennsylvania-born nurse made the health of the people of remote Mitchell County, North Carolina, her life's work. Her courage and persistence attracted the attention of the national press and President Hoover, yet today she is all but forgotten. PMID- 1896318 TI - Can we talk? questions for the Fourth Estate. PMID- 1896319 TI - Celebrating the Bill of Rights in the year of Rust v. Sullivan. PMID- 1896320 TI - On pregnancy tests. PMID- 1896321 TI - Making practice perfect. PMID- 1896322 TI - Coping and health outcomes in spouse caregivers of persons with dementia. AB - The effects of different coping patterns on the physical health, depression, and anxiety experienced by 60 spouse caregivers of persons with dementia were examined, using Lazarus and Folkman's cognitive model of stress and coping. In addition to coping, the model included the following predictors: severity of the patient's memory and behavior problems, caregiver's appraisal of the stressfulness of those problems, and caregiver's appraisal of their options for managing caregiving. The predictors did not explain a significant amount of the variance in caregivers' physical health, but they did explain 43% of the variance in both depression and anxiety. The only coping pattern that added to the explanations was Wishing-Emotive coping, which consisted of the coping subscales of escape-avoidance, confrontive coping, and accepting responsibility. Caregivers' appraisal of stress was a significant predictor of depression and anxiety, but neither the severity of the patients' problems nor caregivers' appraisal of options was a significant predictor of any of the health outcomes. PMID- 1896323 TI - Beliefs about AIDS, health, and illness in low-income white women. AB - A sample of 42 low-income white women were interviewed to describe their beliefs about AIDS and its treatment and to determine whether these beliefs were related to the subjects' general framework of beliefs about illness and its treatment. Content analysis was used to classify data. The causes and treatment of AIDS were categorized as professional sector, popular sector, and traditional sector health care beliefs. Professional sector beliefs included the cause and major modes of transmission and prevention identified by the biomedical system and the public health service. Popular sector misconceptions included beliefs about casual transmission and immunizations. Traditional sector beliefs concerned causes such as contamination and impurities and remedies such as herbs and diet. The respondents' explanations for the causes and treatment of AIDS in these three areas were integrated into a lay explanatory model of illness involving germs, resistance, and the immune system. PMID- 1896324 TI - Maternal employment effects on family and preterm infants at three months. AB - The purpose of this study was to investigate the effects of maternal employment status and the mother's degree of choice and satisfaction regarding her employment status on family functioning and on the preterm infant's development at three months chronologic age. Families with preterm infants (N = 110) were categorized as employed, nonemployed, and on leave of absence based on the mother's employment status at three months postpartum. There were no significant differences across employment groups on family functioning and child development. The infant's motor development was positively correlated with number of hours employed per week and degree of choice for the employed mother families, but negatively correlated with choice for the nonemployed mother families. These results suggest that maternal employment may not be detrimental for infants born prior to term. Indeed, it may be beneficial, especially if the mother has a choice in the matter. PMID- 1896325 TI - Choosing and using contraception: toward a theory of women's contraceptive self care. AB - Thirty women of varying ethnicity and socioeconomic status, who were actively seeking to avoid pregnancy, were interviewed concerning their lifetime experience with contraceptive use. The resulting description, Women's Contraceptive Self Care, was divided into four processes: the central process, Choosing and Using Contraception, and three contextual processes. Forestalling Pregnancy was defined as using contraceptive methods or behaviors to prevent or delay childbearing. Assigning the Burden of Contraceptive Responsibility was defined as assuming responsibility for contraception or shifting that responsibility to a partner. Negotiating with Those who Control Contraception was defined as maneuvering among individuals and agencies that permit or hinder access to contraceptive methods and behaviors. Each process is comprised of thematic clusters and/or themes that are defined and illustrated. PMID- 1896326 TI - Variation in intravaginal pressure measurements. AB - The wide variation in intravaginal pressure measurements of the circumvaginal muscles (CVM) was studied in five subjects under well-controlled conditions. Previous research and clinical observations have indicated that fluctuations in the measurement of intravaginal pressure may be associated with time of day, day of testing, and existing stress factors. Subjects were assessed four times per day, on four consecutive days, for a total of 16 assessments. At each of the 16 conditions for a given subject, 10 CVM contractions lasting 12 seconds each were recorded and the variables, maximum pressure (MP10), peak maximum pressure (PMP), and abdominal pressure were analyzed. The within-subject variance was 15.5 (SD = 3.9); the between-subject variance was 132.4 (SD = 11.5). The effects of day, time, and stressor were analyzed by ANOVA specifically designed for variance estimates; no significant differences were found. The clinical observations that led to the study were not supported when systematically investigated. However, consistent data collection procedures appeared to reduce within-subject variance. PMID- 1896327 TI - Empowering potential: a theory of wellness motivation. AB - Data were collected from 29 individuals who were attempting to initiate and sustain programs of cardiac risk factor modification. Data were analyzed through the technique of constant comparative analysis. Empowering potential, the basic social process identified from the data, explained individual motivation to initiate and sustain cardiovascular health behavior. Empowering potential was a continuous process of individual growth and development which facilitated the emergence of new and positive health patterns. Within the process of empowering potential, individuals use a variety of strategies which guide the initiation and maintenance of health-related change. The process of empowering potential consists of three stages: appraising readiness, changing, and integrating change. Two categories occurred throughout the process of empowering potential: imaging and social support systems. These findings provide a better understanding of how motivated action is initiated and reinitiated over time. PMID- 1896328 TI - Newborn behavioral performance in colic and noncolic infants. AB - The specific purpose of this investigation was to examine the newborn performance of colic and noncolic infants on the Brazelton Neonatal Behavior Assessment Scale (BNBAS). The sample was composed of 119 firstborn infants from healthy, married, white couples. Data were collected prenatally, during the perinatal period, and postnatally from birth through four months of infant age. A total of 38 infants (32%) were believed to have colic. Colicky infants differed significantly from noncolicky infants on one of the seven item clusters, labeled the BNBAS Orientation cluster (p less than .05). PMID- 1896329 TI - Re: 'The effect of lung hyperinflation and endotracheal suctioning on cardiopulmonary hemodynamics'. PMID- 1896330 TI - Linkages between community mental health centers and public mental hospitals. AB - Directors of community mental health centers and superintendents of public mental health hospitals in one state were surveyed to gather data on interagency linkages. Implementation of affiliation agreements, exchange of staff training, and exchange of patient information were investigated. Affiliation agreements tended to be implemented with little difficulty and there was more interagency cooperation than that reported in earlier research. However, exchange of training and staff were still areas of minimal interaction. Geographic proximity was found to have a positive influence and competition a negative influence on cooperation. Further attempts at interagency linkages in the interest of continuity of patient care are recommended. PMID- 1896331 TI - Perceived stress, trait anger, modes of anger expression, and health status of college men and women. AB - Relationships among perceived stress, trait anger (general propensity to become angry), modes of anger expression, and health status were examined in a sample of 720 college students. Although stress was significantly correlated with trait anger and all four modes of anger expression, most correlations were of low magnitude. College men and women did not differ in trait anger, anger-in, or anger-out. Significant gender differences were found in only two modes of anger expression--discussing anger and expressing it somatically (women scoring higher on both). The contribution of anger variables to the variance in health status was negligible. PMID- 1896332 TI - Stress and health in low birthweight infants: a longitudinal study. PMID- 1896333 TI - Regression discontinuity design: alternative for nursing research. PMID- 1896334 TI - Lillian Wald: public health pioneer. PMID- 1896335 TI - Springing the trap. PMID- 1896337 TI - Smoked out. PMID- 1896336 TI - Researching ethics. PMID- 1896338 TI - Back from the USSR. Interview by Linda Davidson. PMID- 1896339 TI - Home economics. PMID- 1896340 TI - Chartered territory. PMID- 1896341 TI - Organ donation. The gift of life. PMID- 1896342 TI - Code of conduct. A double-edged sword? PMID- 1896343 TI - Code of conduct. Private dilemma. PMID- 1896344 TI - Music hath charms.... PMID- 1896345 TI - Cancer nursing research. PMID- 1896346 TI - Nurses are patients, too. PMID- 1896347 TI - Systems of life. Reproductive system--1. PMID- 1896348 TI - Use of environmental seclusion monitored. PMID- 1896349 TI - Bladder symptoms and urinary infections. PMID- 1896350 TI - Living with rheumatoid arthritis. PMID- 1896351 TI - Nurse education. A new style of management. PMID- 1896352 TI - How to ... use computer-based training. PMID- 1896353 TI - The catheter debate. PMID- 1896354 TI - Catheters. Looking at the evidence. PMID- 1896355 TI - P3: human environment. Part (I): Public health and personal health. PMID- 1896356 TI - Curing racism? PMID- 1896357 TI - The storyteller. Interview by Bernadette Friend. PMID- 1896358 TI - Under scrutiny. PMID- 1896359 TI - For the record. PMID- 1896361 TI - Open learning. Building up steam. PMID- 1896360 TI - Fit for baby. PMID- 1896362 TI - Open learning. Something for everyone. PMID- 1896363 TI - Hysteria. PMID- 1896364 TI - Power can be healthy. PMID- 1896365 TI - Just a song at twilight. PMID- 1896366 TI - Trial and tribulation. PMID- 1896367 TI - Step by painful step. PMID- 1896368 TI - Computing in practice. The QA solution. PMID- 1896369 TI - Teaching mouth care. PMID- 1896370 TI - Preferred teaching and learning strategies. PMID- 1896371 TI - The Bradford Somatic Inventory. PMID- 1896372 TI - The Journal of Infection Control Nursing. Looking into the refrigerator. PMID- 1896375 TI - Forum slams AIDS policy. PMID- 1896374 TI - The Journal of Infection Control Nursing. Coming unstuck. PMID- 1896373 TI - The Journal of Infection Control Nursing. Protecting with plastic aprons. PMID- 1896376 TI - [Use of intravenous immunoglobulins in pediatrics]. AB - Intramuscular Immunoglobulin (IMIG) have been used for 40 years in substitution therapy for antibody deficiencies and as prophylaxis for and treatment of several infectious diseases. Modified and intact intravenous immunoglobulin preparations (IVIG) have now been available for more than 10 years: only the intact product express full Fc- mediated functions with a biological half-life of IgG (3-4 weeks). These preparations have constituted an important achievement in the treatment of humoral immunodeficiencies also resulting in a dramatic improvement of the prognosis. The use of IVIG has also modified the therapeutic approach to several secondary and acquired immunodeficiencies. Treatment with IVIG for immune modulation in several diseases is investigated: substantial data indicate a useful role in selected cases of idiopathic thrombocytopenic purpura, Kawasaky disease and in some neurologic diseases. IVIG are substantially safe and severe side effects have been rarely reported. PMID- 1896377 TI - [Primary immunodeficiency 1991: new uses and prospects of genetic counseling]. AB - In the last fifteen years, therapeutic use of intravenous immunoglobulin on one hand, and of bone marrow transplantation on the other, have largely modified survival rate and prognosis for many primary immunodeficiency diseases. At the same time, major advances in molecular genetics have allowed mapping of several immunodeficiency genes and made prenatal diagnosis feasible. Furthermore, for many X-linked immunodeficiencies, carrier detection can be also accomplished by means of analysis of the pattern of X-chromosome inactivation. As a whole, these techniques have substantially contributed to a more accurate genetic counseling in the families. PMID- 1896378 TI - [Cellular and molecular therapy in severe combined immunodeficiencies]. AB - Severe combined immunodeficiencies are usually fatal diseases unless affected children are admitted to protective isolation unit or unless the underlying immunological defect is treated by transplanting bone marrow from an healthy donor. The patients present, with early onset, life-threatening infections from fungal, viral or bacterial agents. Since only a minority of patients has an HLA identical donor, recently other strategies have been devised including bone marrow transplantation from donors other than HLA-identical within the family or from HLA-non identical family members or from HLA-matched unrelated donors included in the International Bone Marrow Volunteers' Registry. In these cases, in order to realize this approach the "purging" of T-cells of the HLA-non identical donor bone marrow is necessary. Overall survival after HLA-identical BMT is 76%, when all BMT of the European multicenter analysis are considered, while in BMT from non-identical donors is 56%. Recently particular cases of SCID caused by enzyme deficiency, such as adenosine-deaminase (ADA), have been treated by molecular therapy with administration of polyethylene glycol (PEG) conjugated ADA: PEG protects from degradation and inhibits clearance of the enzyme. This approach, already realized in 15 children, allows reconstitution of cellular and humoral immunity, as demonstrated by one case treated by our group. PMID- 1896379 TI - [Prethrombotic states in pediatrics]. PMID- 1896380 TI - [Iron deficiency in children: which is the correct therapy?]. AB - Iron is essential for human metabolism. Under normal circumstances its homeostasis is strictly kept by absorption and excretion through genitourinary, gastrointestinal tracts and skin losses. In several systemic disorders, dietary iron is insufficient to keep such a dynamic balance: development of iron deficiency may be due to increased requirements, decreased intestinal absorption, inadequate dietary uptake. Low birth weight newborns, children and adolescents are at increased risk for developing iron deficiency. Although clinical aspects may vary, hematochemical findings show a three-step gradual progression. In a first step iron deficiency is diagnosed by serum ferritin level which will be under 10-20/micrograms/ml showing a depletion of total body iron stores. In a second step progressing iron deficiency will be assessed by lowered serum iron and increased unsaturated serum transferrin, serum iron bound to transferrin and erythrocyte protoporphyrin IX. Scanty clinical signs are still available. In a third step while clinical findings show a complete features of iron deficiency anemia (weakness, fatigue, palpitations, etc.), laboratory findings show morphologic alterations in red cells (hypochromia and microcytemia), together with the aforementioned disorders in ferrokinetics. Iron deficiency anemia responds very effectively to treatment due a correct etiological diagnosis, crucial to a through therapy tending to first eliminating the causes of it. Prophylaxis against iron deficiency anemia is required in prematurely born and low birth weight infants because of doubled iron requirements. After the second month of life diet is supplemented with 2-4 mg/kg/die of ferrous iron orally along the first year of life. PMID- 1896381 TI - [Is appearance of bronchiolitis affected by environmental and genetic factors?]. AB - We have respectively studied 39 patients (22 males and 17 females) in an age below 18 months affected with bronchiolitis and hospitalized in the "Istituto di Pediatria B (Institute of Pediatrics B) of Palermo's University from november 1986 to april 1987. The parameters we have considered are: 1) the family predisposition to atopy; 2) the type of suckling; 3) the social and economical conditions pointed out the overcrowding index; 4) the every day consumption of cigarettes by the cohabitant relatives; 5) the total dosage of IgE. The data of the hospitalized patients have been compared with the ones pointed out in an "examination group" formed by 64 subjects (36 males and 28 females). The frequency of family predisposition to atopy in our patients has turned out to be inferior to the group examined. The overcrowding index allowed a superposition in the two groups. Among our patients we have found a smaller amount of breast-fed babies and a greater number of smoking cohabitant in comparison with the controls even if the differences statistically were not significant. The serial IgE levels, carried out in 29 patients, resulted high in 6 children (20.69%). PMID- 1896382 TI - [Dehydrated child]. AB - Dehydration, in childhood as in adulthood, may origin from an inadequate water ingestion or an excessive water elimination. Causes may be found in fever, vomiting, scalds, pulmonary hyperventilation, diabetes. Water loss during acute diarrhea in children can be even 6-7 times higher in comparison with an healthy child. Together with water, electrolytes are lost. We differentiate dehydration in isonatremic d. (70% of cases), hyponatremic d. (10%) and hypernatremic d. (20%) basing on Sodium loss. Important dehydration causes severe clinical symptoms as shock, renal and cardiocirculatory failure, convulsion, coma. Symptoms at the central nervous system level derivate both from hyperosmolarity in brain cells and from thrombosis or hemorrhages in subdural sites. Dehydration, following acute diarrhea, is slight when weight loss is lower than 5%. The child health conditions still remain good. Dehydration become moderate if weight loss reaches 5% and the child starts suffering. When the weight loss reaches 10%, dehydration is now severe and circulatory deficiency becomes evident. When it is higher than 10%, prognosis is very severe and shock and coma may be observed. In the present work, we illustrate the different ways of rehydration after acute diarrhea. Initially, oral rehydration must be established with one of the oral solutions, differing each other for amount of electrolytes and glucose. Recently, a new solution, "supersolution", has been presented differing from the other ones for electrolytes concentration and for the presence of rice starch instead of glucose. In most cases of diarrhea, oral rehydration appears adequate but sometimes an intravenous rehydration becomes necessary, e.g. in case of vomiting, CNS depression and in any case of severe gastroenteric symptomatology.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1896383 TI - [Comparison of an oral rehydration solution (ORS 90) and a "supersolution" during acute infantile diarrhea]. AB - As acute diarrhoea gives rise to a loss of water and electrolytes, the most effective therapy results the oral rehydration. Harrison and Darrow tried this way first. Only in the years '60 we began to use oral rehydration commonly. Usually, solutions contain glucose, Na, K, Cl, Bicarbonate in various concentration. When glucose is replaced by rice starch or when amino acid are added, then we have a "supersolution". Nutrients intake provides more calories and increases absorption Na-depending. We used one of these new "supersolutions". Two groups of children, hospitalised for acute diarrhoea, were treated with different rehydration solutions. The first one (Dicodral Forte), prepared according to the WHO, contains glucose and electrolytes as we know. The second one (Amidral) has rice starch instead of glucose and presents a lower concentration of Na and Cl. The present study looked over: A) Weight increase from the first to the third day of hospitalisation in our department. B) Duration of diarrhea. C) Number of stools. D) Haematological values before and after rehydration. All the patients ingested the same amount of solution. Children which received WHO's solution presented diarrhea longer than others (2.55 +/- 2.06 vs 2.2 +/- 1.1 days). Number of stools was below average too (3.05 +/- 2.64 vs 2.8 +/- 1.5). Refeeding was done employing the same milk used in former times. AMIDRAL was used to dilute the milk when it was possible. Most important result is the increase of weight we had using this "supersolution". 15/20 children which received AMIDRAL showed an increase of their weight as shown in Tab. 1. PMID- 1896385 TI - [Hypophosphatasia: a family study]. AB - Diagnostic pathway and 5-years follow-up of a case of childhood-form hypophosphatasia (a severe form of vitamin D resistant rickets) are described. Family study led to the identification of five affected relatives (father, sister, paternal uncle, first-cousins), two with severe clinical evidence. Inheritance pattern in this family is compatible with autosomal dominant transmission. PMID- 1896384 TI - [Chondroid hamartoma of the thoracic wall: apropos of a case treated by extensive surgical exeresis]. AB - The Authors describe a case of chest wall hamartoma, very rare in infants and usually present at birth. This lesion, histologically, is benign. Surgical ablation is mandatory and curative, but the ablation of the tumor and the reconstruction of the large residual parietal defect are sometimes very difficult. In this case the surgical treatment was successful and the reconstruction of the thoracic cage was obtained with a particular surgical technique. PMID- 1896386 TI - [Benign recurrent intrahepatic cholestasis. Description of a clinical case]. AB - We present the clinical case of an 8 years old boy affected by episodes of severe recurrent jaundice, preceded by intense itching with clinical and biochemical signs of cholestasis, diagnosed as benign recurrent intrahepatic cholestasis (B.R.I.C.), or Summerskill's syndrome. This was first described by this author in 1959. The syndrome appears as a rare form of cholestatic jaundice of unknown pathogenesis, which in 80% of cases shows up before the age of 20. Its clinical characteristics are episodes of severe jaundice preceded by intense itching with biochemical signs of cholestasis which rise with no apparent cause and which recover spontaneously and are intervalled by asymptomatic periods which last months or years. During this time there is also a regression of the chemical and histological evidence of cholestasis. The diagnosis of B.R.I.C. can be made after having excluded the other congenital or acquired causes of intrahepatic cholestasis according to the recurrent character of the jaundice and to the hepatic biopsy. PMID- 1896387 TI - [Extralobar pulmonary sequestration in children: presentation of a case]. AB - The pulmonary sequestration is an anatomical condition with as isle of pulmonary tissue independent from tracheobronchial tree. This tissue has an independent artery originated from aorta. Anatomically we can have two types of sequestration. The first is the condition of an isle of pulmonary tissue included without any separation in the lobe; this condition in named intra-lobar sequestration. On the other hand we have a second condition with an isle of independent pulmonary tissue surrounded with independent pleura; the last one is named extra-lobar sequestration. In the present article the authors describe a case of extralobar sequestration in a two years old girl. The symptoms presented by the girl were hyperpyrexia, tough and recurrent bronchopulmonary infections. The girl underwent surgery removal of sequestration. The authors describe their experience, the importance of symptomatology and the anatomo-pathologic characteristics of this lesions. PMID- 1896388 TI - [Genetic role in hernia of the esophageal hiatus. Description of the disease in 2 brothers]. AB - Two brothers born 15 years apart from normal healthy parents were affected by esophageal hiatus hernia diagnosed at 4 and 8 months respectively. We found 37 other families with more than one member affected by EHH reported in the literature. Since the anomaly often runs asymptomatic, familiarity is probably more frequent than generally thought. The type of inheritance is still uncertain, but a multifactorial etiology is the most likely explanation. PMID- 1896389 TI - [An atypical case of juvenile polyps]. AB - The authors report a case of Juvenile Polyps set up early in the first months of life, whose bleeding leads to a severe iron deficiency anemia. The atypical seat of the polyp (the jejunal tract) vanished the usual instrumental diagnostic procedures. PMID- 1896390 TI - [Gastroduodenal ulcer: apropos of 2 cases in childhood]. AB - Authors describe two cases concerning primary peptic disease: gastric and duodenal ulcer, observed in two children. Clinical pictures, diagnostic and therapeutic methods are described. In this paper we discuss particularly new etiopathogenetic and therapeutic factors about peptic disease. PMID- 1896391 TI - [Secondary pulmonary hypertension--certain diagnostic and therapeutic aspects]. PMID- 1896392 TI - [Renin-angiotensin-aldosterone system (RAA) and vasopressin secretion in patients with chronic renal failure]. AB - Influence of blockade converting enzyme on plasma renin activity (PRA), aldosterone and vasopressin secretion in 12 hemodialyzed patients with chronic renal failure and in 21 healthy subjects was observed. Our observation were provided during bed rest and water immersion tests. We didn't observe statistically significant influence PRA (increase after converting enzyme blockade) on vasopressin secretion in patients with chronic renal failure and in healthy subjects. Correlation between PRA and vasopressin secretion was absent. PMID- 1896393 TI - [Effect of secondary hyperparathyroidism upon serum hydroxyproline in patients with renal failure]. AB - Diagnosis of secondary hyperparathyroidism in 12 patients treated with repeated hemodialysis was established on the basis of clinical symptoms and biochemical studies. Following subtotal parathyroidectomy the resected parathyroid specimens were examined histologically. The diagnostic value of total and free hydroxyproline in the serum in secondary hyperparathyroidism was found to be similar to the diagnostic value of the parathyroid hormone. The correlation with histological diagnosis was from 93% to 100%. After parathyroidectomy a significant decrease in the concentrations of total and free hydroxyproline in the serum was noted being the quickest within the first six months following the resection. The decrease in the concentrations of total and free hydroxyproline in the serum in patients with secondary hyperparathyroidism are valuable diagnostic markers of bone collagen metabolism and bone repair following parathyroidectomy. PMID- 1896394 TI - [Effect of peritoneal dialysis and hemodialysis on respiratory function in patients with chronic renal failure]. AB - Respiratory function was studied in 17 patients with chronic renal failure treated by peritoneal dialysis and in 18 patients treated by hemodialysis. During peritoneal dialysis and hemodialysis we observed impaired respiratory function and changes in lung volumes. Decrease of the arterial oxygen tension during peritoneal dialysis may be due to the intraabdominal fluid volume, in patients treated by hemodialysis--to respiratory muscle weakness. PMID- 1896395 TI - Treatment of renal anaemia by recombinant human erythropoietin. PMID- 1896396 TI - [Subcutaneous administration of recombinant human erythropoietin (R-EPO) in the treatment of anemia in predialysis patients with chronic renal failure]. AB - 10 anemic (HB less than 9.0 g/dl) predialysis patients with chronic renal failure were treated for three months with s.c. administration of r-Epo. Blood morphological parameters were estimated using hematological autoanalyser Technicon H1. An increase of the mean hemoglobin (Hb) level from 8.39 to 10.57 g/dl was observed. In 8 patients Hb concentration after 3 months therapy ranged from 9.4 to 12.7 g/dl, but in the remaining two of them Hb was lower than 9.0 g/dl. Appearance of a high percentage of hypochromic erythrocytes is probably the most characteristic response to r-Epo treatment. This phenomenon was caused by iron deficiency. A significant increase of serum creatinine and BUN levels were observed in treated patients, without the concomitant decrease of endogenous creatinine clearance. No clinical symptoms suggesting deterioration of the renal function were observed. Subcutaneous therapy with r-Epo appeared an effective and convenient method of treatment of anemia in predialysis patients. PMID- 1896397 TI - [Evaluation of erythropoiesis under the influence of recombinant human erythropoietin (R-EPO) in dialyzed patients]. AB - 5 deeply anemic (Hb less than 8 g/dl, Ht less than 25%) dialyzed patients with chronic renal failure were treated during four months with r-Epo. Blood cells morphological parameters were estimated using hematological autoanalyser Technicon H1. Satisfactory increase of the Hb levels and RBC counts were observed in 4 patients, in one the improvement was insignificant. We observed three types of response to r-Epo treatment: 1) macrocytic type, 2) hypochromic type, and 3) non-hypochromic type, without lasting macrocytosis. Our results suggest that type of erythropoiesis depends on other active biological substances (iron, folic acid, vit. B12) necessary for correcting erythropoiesis. r-Epo administration appeared to be a safe and effective method of anaemia treatment in dialyzed patients. Its administration eliminated blood transfusion for six months. PMID- 1896398 TI - [Plasma erythropoietin levels of kidney transplant patients in the early period after transplantation]. AB - Plasma erythropoietin (EPO) levels were assessed in 51 uraemic patients immediately after kidney transplantations and in 16 healthy subjects. Before transplantation EPO levels were significantly higher than in normals. In patients with acute renal failure of the transplanted kidney, a significant increase of plasma EPO level was noticed. Such an increase of plasma EPO was absent in patients with a normally functioning kidney transplant. In these last patients normalization of plasma EPO was found during the first month after transplantation. No significant correlation was found between plasma EPO level and the haematocrit value in kidney transplant patients. From results obtained in this study it seems, that factors other than EPO are also involved in the pathogenesis of anaemia in patients at the early phase after kidney transplantation. PMID- 1896399 TI - [Plasma erythropoietin levels in patients with stabilized function of the transplanted kidney]. AB - Plasma erythropoietin level was assessed in 96 kidney transplant patients with stabilized function of the graft 3 months up to 5 years after transplantation and in 16 healthy subjects. In kidney transplant patients on CyA or azathioprine respectively, plasma erythropoietin levels were significantly higher during the first three months after transplantation than in normals. Normalization of erythropoietin levels were observed 6 to 12 month after kidney transplantation. As compared with patients on CyA, in azathioprine treated patients plasma erythropoietin levels were significantly higher 12 to 60 months after transplantation. These elevated erythropoietin levels in azathioprine treated patients seem to be due also to factors other than higher prednisone dosage. PMID- 1896400 TI - [Plasma erythropoietin levels in kidney transplant patients with impaired function of the renal graft]. AB - In 81 patients with failing kidney transplant, plasma levels of erythropoietin, iron, ferritin and TIBC were assessed. Progression of failure of the excretory function of the kidney transplant was accompanied by decreasing Hb and Ht values but increasing plasma levels of erythropoietin. In all examined patients presence of iron deficiency could be excluded. Results obtained in this study suggest that relative erythropoietin deficiency is the major cause of anaemia in patient with a failing kidney transplant. PMID- 1896401 TI - [Plasma erythropoietin levels in patients with noninflammatory acute renal failure]. AB - Plasma levels of erythropoietin (EPO) were estimated in 14 patients with noninflammatory acute renal failure during the oliguric anuric and polyuric phase respectively. During the anuric oliguric phase plasma EPO levels were 4 times higher than in healthy subjects, while during the polyuric phase normal plasma levels were found in spite of the presence of anaemia. Results presented in this paper suggest presence of an abnormal feedback between EPO secretion and degree of anaemia in patients with acute noninflammatory renal failure both during the anuric/oliguric and polyuric phase respectively. Abnormal EPO secretion does not seem to be the only or even dominant factor involved in the pathogenesis of anaemia in patients with noninflammatory acute renal failure. PMID- 1896402 TI - Changes in rheology and red blood cell function under recombinant human erythropoietin therapy. AB - The rh-EPO is a potent drug to treat renal anaemia. RBC aggregation is not influenced by the rh-EPO therapy. Membrane elasticity and RBC deformability improve remarkably after rh-EPO which might benefit microcirculation. Rh-EPO therapy can not prolong RBC life span. Obviously uremic milieu alone determines RBC life time. Rh-EPO treatment corrects renal anemia by increasing the number of RBC and the RBC volume. PMID- 1896403 TI - [Activity of selected neutrophil enzymes of patients maintained on hemodialysis and treated with erythropoietin (rHu EPO)]. AB - The peroxidase, alkaline phosphatase, acid phosphatase, beta-glucuronidase and N acetyl-beta-D-glucosaminidase activity was assessed using a semiquantitative cytochemical methods in peripheral blood neutrophils from 10 maintenance haemodialysed patients treated with recombinant human erythropoietin (rHu EPO) due to severe anaemia. The examination was performed immediately prior to rHu EPO treatment, after 10 weeks and 32 weeks of therapy. A statistically significant increase in the beta-glucuronidase and N-acetyl-beta-D-glucosaminidase activity was observed after 10 weeks, while all the enzymes studied except peroxidase showed a significant elevation of their activity after 32 weeks of the treatment as compared with the values obtained prior to therapy. PMID- 1896404 TI - [Effect of erythropoietin on some rheological and biochemical properties of blood in dialysed patients with irreversible kidney failure. Preliminary results]. AB - 6 patients with symptomatic renal anaemia treated with haemodialysis (3F, 3M, aged 41 +/- 17 years) were given r-Hu EPO in initial dose of 50 U/kg, modified during the treatment, according to the Hkt, and Hgb values. Some biochemical and rheological properties of blood taken before treatment showed: normochromic and normocytic anemia with Hkt 22.7 +/- 1.7% Hgb 6.81 +/- 1.6 g% and normal reticulocytosis: significant (p less than 0.001) decrease of whole blood viscosity (WBV) at low shear rate (2.25 x sec-1) and high shear rate (225 x sec 1) related to Hkt values, and significant increase of red celles aggregation (RCA) (p less than 0.02) in comparison to healthy persons. Plasma viscosity (PV), serum fibrinogen, protein and albumin were normal. In 4 patients treated with r Hu EPO for 12 weeks at least, we observed an increase Hkt to 36.7 +/- 2% and Hgb to 11.2 +/- 1.2 g% and a significant increase of WBV at high shear rate (p less than 0.05), normalization of RCA and improvement of the filtrability of whole blood. No side effects were observed, especially insufficient control of blood pressure. Our preliminary results indicate that our treatment of renal anemia with r-Hu EPO was clinically effective, safe and had positive influence on blood rheology. PMID- 1896405 TI - [Participation of polyphosphoinositides in the transfer of intracellular information]. PMID- 1896406 TI - [Interactions between Eco RI restriction endonuclease and DNA]. PMID- 1896407 TI - [Reactions of an antineoplastic drug cis-diamminedichloroplatinum(II) with DNA]. PMID- 1896408 TI - Hepatotoxicity induced by the Oriental hornet (Vespa orientalis) venom sac extract. AB - Experiments were performed to investigate the nature of the in vitro and human liver damage exposed to hornets' acute or repeated stings. The hornet investigated is the one ubiquitous in Israel - Vespa orientalis. Experiments were performed in living cats and rats, after single or multiple exposures to venom sac extracts (VSE) and in various doses. The injury was demonstrated by the increased levels of enzymes, bile acids and cholesterol in serum. Also measured was Beta-N-acetyl hexosaminidase (BNAH) which probably is the only biochemical indicator available of Kupffer-cell function. This, too, was found increased. Other experiments consisted of perfusion of the isolated, intact, rat liver in situ with measurements of enzyme leakage into perfusate and of bile flow. Another set of experiments involved the effects of VSE on in vitro monolayer tissue culture of rat embryos' livers. We examined damage to organelles and compared the damage produced by intact VSE with that produced by the venom sac extract after treatment by heat or dialysis. Light morphology, special stains, electron microscopy and morphometry were all performed. In the first set of experiments no shock was observed in cats and rats exposed to VSE. The increases in enzymes' activity in serum and liver perfusion fluid were significant. Histochemistry indicated decrease of hepatic glycogen and of cellular succinic dehydrogenase as well as hepatic fat infiltration and an increase of alkaline phosphatase activity in liver cells close to the bile capillaries.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1896409 TI - Progression of exencephaly to anencephaly in the human fetus--an ultrasound perspective. AB - Exencephaly as a precursor of anencephaly is well delineated in animal studies. In humans, a similar though unproven embryologic sequence is postulated. In the case reported, serial ultrasound studies allowed us to identify a 16-week human exencephalic fetus and observe the cephalic changes during its progression to a classic anencephalic appearance. PMID- 1896411 TI - Prenatal diagnosis of inborn errors in peroxisomal beta-oxidation. AB - In recent years, an increasing number of inherited diseases in man have been recognized in which there is an impairment in the peroxisomal beta-oxidation of very-long-chain fatty acids. In general, these disorders are associated with severe neurological and physical abnormalities and death within the first years of life. In this paper we describe our experience with regard to the prenatal diagnosis of a number of different inborn errors of peroxisomal beta-oxidation. Eleven pregnancies at risk were monitored by measuring very-long-chain fatty acid levels as well as very-long-chain fatty acid beta-oxidation in cultured chorionic villous fibroblasts and/or amniotic fluid cells. Five affected fetuses were identified. It is concluded that prenatal diagnosis in this group of diseases can be done reliably using cultured chorionic villous fibroblasts or amniotic fluid cells. PMID- 1896412 TI - Prenatal diagnosis in multiple gestation: 20 years' experience with amniocentesis. AB - Three hundred and thirty-nine cases of multiple gestation underwent prenatal diagnosis by amniocentesis. The spontaneous abortion rate (to 28 weeks) in this group was 3.57 per cent compared with our singleton abortion rate of 0.60 per cent. The perinatal mortality rate (PMR) and prematurity rate were not different from the singletons, and compared favourably with the PMR reported in the literature for multiple gestations which did not undergo any intervention during pregnancy. This increased abortion rate following amniocentesis may only represent the increased natural loss rate in multiple gestations, and not indicate any increased risk added by the procedure. PMID- 1896410 TI - The normal fetus of an acardiac twin pregnancy: perinatal management based on echocardiographic and sonographic evaluation. AB - Experience with three prenatally diagnosed pregnancies complicated by an acardiac twin reveals that ultrasonography and echocardiography are helpful in detecting early signs of in-utero congestive heart failure in the normal twin. The use of Doppler blood flow analysis to determine direction of blood flow, post-mortem placental and fetal angiography, and umbilical cord blood gas determination provided proof that retrograde arterial perfusion occurs in the acardiac fetus. In a fourth pregnancy, an experimental approach to occlude the acardiac twin's umbilical cord was attempted, but was unsuccessful. PMID- 1896413 TI - Pallister Killian--mosaic tetrasomy 12 p syndrome. Another prenatally diagnosed case. AB - A new case of mosaic tetrasomy 12 p (46,XY/47,XY, +i12 p), diagnosed during pregnancy from ultrasonographic signs, is reported. We emphasize the peculiar position of the diaphragmatic hernia in this syndrome. Its presence or absence determines the vital prognosis and the age of diagnosis. The knowledge of its possible association with tetrasomy 12 p can contribute considerably to the neonatal diagnosis by directing the work of the cytogeneticist to tissue cultures which enable him to detect the presence of the tetrasomy. PMID- 1896414 TI - Significance of very low maternal serum human chorionic gonadotropin in prenatal diagnosis of triploidy. PMID- 1896415 TI - Mosaic isochromosome 20q. PMID- 1896416 TI - Randomized clinical trial of transabdominal versus transcervical chorionic villus sampling methods. AB - The relative advantages and disadvantages of transabdominal (TA) and transcervical (TC) chorionic villus sampling (CVS) in terms of fetal risks and efficacy were evaluated in a clinical trial conducted on 1194 women randomized at 7-12 weeks' gestation. The results of the study indicate that, if any, the relative risk of fetal loss following either procedure is less than double that of the alternative technique when performed by a skilled operator. Overall, the fetal loss rate (spontaneous abortions following randomization, terminations of pregnancy, and perinatal deaths) is 16.5 and 15.5 per cent, respectively, among women allocated to TA- and TC-CVS. The two procedures are equally effective, although TA-CVS is associated with a significantly lower rate of repeat device insertions; on the other hand, a higher weight of chorionic tissue is obtained, on average, with TC-CVS. Bleeding is more common following TC-CVS, while peritoneal reaction developed only after TA-CVS. No diagnostic problems specifically related to one sampling technique were identified. PMID- 1896417 TI - Early amniocentesis at 11-14 weeks' gestation for the diagnosis of fetal chromosomal abnormality--a clinical evaluation. AB - Early amniocentesis between 11 and 14 weeks' gestation was offered to 110 women at risk of a chromosomally abnormal fetus due to maternal age. Four were found to be unsuitable for the procedure, and 106 early amniocenteses were performed. In 102 cases, clear amniotic fluid was obtained with a single tap. There were two dry taps and two bloodstained taps; sampling was repeated in three of these cases before 15 weeks. In the fourth case, placental biopsy was performed at 16 weeks. Thus, we were able to obtain a satisfactory sample in all but three cases (2.8 per cent). Karyotyping of cells harvested from the early amniotic fluid samples was successful in all the 105 cases. Cell culture from the initial samples revealed a normal karyotype in 99 cases, two balanced translocations, two tetraploid karyotypes, and two cases of pseudomosaicism. Of the 105 pregnancies successfully sampled, there have been two losses to date (1.8 per cent). Two further patients presented with premature rupture of membranes, both pregnancies having successful outcomes. Sixty-two babies have delivered to date, with four congenital anomalies. There were no respiratory problems. Twenty-nine pregnancies are continuing without known complications, and details are not yet available on the remaining 12. The results indicate that early amniocentesis may replace the traditional test at 15-17 weeks. PMID- 1896418 TI - Induction of fetal lung maturation with intra-amniotic thyroxine in multiple pregnancy. AB - Two premature triplet pregnancies underwent repeated treatment aimed at acceleration of individual fetal lung maturity while administering intravenous tocolytic treatment. From the early third trimester, repeated amniocenteses were used for intra-amniotic administration of thyroxine to each sac, while the individual fetal lung maturation rate was determined by surfactant microviscosity until lung maturity was achieved. PMID- 1896419 TI - Pancreatic and sacral agenesis in association with maternal diabetes mellitus: case report. PMID- 1896420 TI - Expression of fragile-X in a female fetus diagnosed after chorionic villus sampling. AB - Study of different tissues of an aborted female fetus showed similar levels of fragile-X expression (6.3-9.2 per cent) and of early replication of the FRAXA positive cells (50-66 per cent) in fetal tissues. Different culture media did not significantly affect either investigation. It is suggested that the distribution of X-inactivation in FRAXA-positive chorionic villus cells of a female fetus might indicate her future phenotype. PMID- 1896421 TI - Partial trisomy 22q12----qter in prenatal diagnosis. AB - Ultrasound examination of a 27-year-old primigravida at 26 weeks' gestation revealed fetal growth retardation, malformation of the ventricular septum, and a neck fold. Chromosome analysis of the amniotic fluid showed an abnormal 46,XY karyotype with an obvious metacentric chromosome 17. Chromosome analysis of the mother revealed a balanced t (17;22) (p13;q12) translocation. The fetus thus has a rare familial duplication 22q12----qter. Eight live-born and severely malformed infants with this duplication have been reported in the literature. PMID- 1896422 TI - Prenatal paternity testing by DNA analysis. AB - Prenatal paternity testing was evaluated by DNA analysis in chorionic villus biopsies obtained during the 7th-22nd weeks of gestation. Using highly polymorphic variable number of tandem repeats (VNTR) probes, we analysed four cases consisting of mother/child/alleged father trios. In all cases, we were able to detect maternal and paternal alleles and could establish or exclude paternity. The application of DNA analysis represents a new important diagnostic aid for all cases that require a prenatal identification of paternity. PMID- 1896423 TI - Prenatal diagnosis of microcephaly. PMID- 1896424 TI - Projection of Monte Carlo and molecular dynamics trajectories onto the normal mode axes: human lysozyme. AB - A method is presented to describe the internal motions of proteins obtained from molecular dynamics or Monte Carlo simulations as motions of normal mode variables. This method calculates normal mode variables by projecting trajectories of these simulations onto the axes of normal modes and expresses the trajectories as a linear combination of normal mode variables. This method is applied to the result of the molecular dynamics and the Monte Carlo simulations of human lysozyme. The motion of the lowest frequency mode extracted from the simulations represents the hinge bending motion very faithfully. Analysis of the obtained motions of the normal mode variables provides an explanation of the anharmonic aspects of protein dynamics as due first to the anharmonicity of the actual potential energy surface near a minimum and second to trans-minimum conformational changes. PMID- 1896425 TI - Relaxation data in NMR structure determination: model calculations for the lysozyme-Gd3+ complex. AB - The effect of including paramagnetic relaxation data as additional restraints in the determination of protein tertiary structures from NMR data has been explored by a systematic series of model calculations. The system used for testing the method was the 2.0 A resolution tetragonal crystal structure of hen egg white lysozyme (129 amino acid residues) and structures were generated using a version of the hybrid "distance geometry-dynamic simulated annealing" procedure. A limited set of 769 NOEs was used as restraints in all the calculations; the strengths of these were categorized into three classes on the basis of distances observed in the crystal structure. The values of 50 phi angles were also restrained on the basis of amide-alpha coupling constants calculated from the X ray structure. Five sets of 12 structures were determined using differing sets of paramagnetic relaxation data as restraints additional to those involving the NOE and coupling constant data. The paramagnetic relaxation data were modeled on the basis of the distances of defined protons from the crystallographic binding site of Gd3+ in lysozyme. Analysis of the results showed that the relaxation data significantly improved the correspondence between the set of generated structures and the crystal structure, and that the more well defined the relaxation data, the more significant the improvement in the quality of the structures. The results suggest that the inclusion of paramagnetic relaxation restraints could be of significant value for the experimental determination of protein structures from NMR data. PMID- 1896426 TI - Side chain-backbone hydrogen bonding contributes to helix stability in peptides derived from an alpha-helical region of carboxypeptidase A. AB - Recently, Presta and Rose proposed that a necessary condition for helix formation is the presence of residues at the N- and C-termini (called NTBs and CTBs) whose side chains can form hydrogen bonds with the initial four amides and the last four carbonyls of the helix, which otherwise lack intrahelical hydrogen bonding partners. We have tested this hypothesis by conformational analysis by circular dichroism (CD) of a synthetic peptide corresponding to a region (171-188) of the protein carboxypeptidase A; in the protein, residues 174 to 186 are helical and are flanked by NTBs and CTBs. Since helix formation in this peptide may also be stabilized by electrostatic interactions, we have compared the helical content of the native peptide with that of several modified peptides designed to enable dissection of different contributions to helix stability. As expected, helix dipole interactions appear to contribute substantially, but we conclude that hydrogen bonding interactions as proposed by Presta and Rose also stabilize helix formation. To assist in comparison of different peptides, we have introduced two concentration-independent CD parameters which are sensitive probes of helix formation. PMID- 1896427 TI - Free energy calculations on binding and catalysis by alpha-lytic protease: the role of substrate size in the P1 pocket. AB - We present free energy calculations using molecular dynamics on different substrates of alpha-lytic protease in the gas phase, in solution, while forming a noncovalent Michaelis complex with the enzyme, and in a tetrahedral structure representing a transition state/intermediate for acylation by the enzyme. Various P1 substrates were studied, with P1 = Gly, Ala, Val, and Leu. In qualitative agreement with experiment, the enzyme was calculated to bind and catalyze most effectively substrates with P1 = Ala over those with P1 = Gly, Val or Leu. Also, the calculated relative solvation free energies of Gly----Ala and Ala----Val were in qualitative agreement with experimental values in corresponding model systems. However, the level of quantitative agreement with experiment achieved in our earlier study of relative binding and catalysis of native subtilisin and an Asn 155----Ala mutant was not achieved. We surmise that this is due to the greater difficulty in quantitatively simulating effects that are predominantly van der Waals and hydrophobic compared to those that are hydrogen bonding/electrostatic. PMID- 1896428 TI - Modelling the three-dimensional structure and electrostatic potential field of the two Cu,Zn superoxide dismutase variants from Xenopus laevis. AB - The crystallographic structure of bovine superoxide dismutase has been used as a template for the graphic reconstruction of the three-dimensional structures of the two Xenopus laevis variants (Schinina, M.E. et al. Arch. Biochem. Biophys. 272:507-515, 1989). In these models the structure-essential residues maintain their position and their structural role, and the interactions between the subunits and the close packing within the beta-barrel are maintained with conservative substitutions and even increased with "aromatic pairs." Because of the same topological motif and surface location of charges, arising from the model building of the two variants with respect to the bovine enzyme, we have calculated the electrostatic potential fields around the models of the two Xenopus laevis variants by numerically solving the Poisson-Boltzmann equation. We show that conservation of a specific space-relationship of charges maintains the potential field pattern already observed in the bovine enzyme, where a negative potential field surrounds the protein surface and specific positive regions wrap up the copper center active site. This electrostatic potential field distribution supports the idea that electrostatic interactions control, like in the bovine enzyme, the mechanism of enzyme-substrate recognition in the Xenopus laevis Cu,Zn superoxide dismutases, suggesting that coordinated mutation of charged residues has occurred in the evolution of this enzyme. PMID- 1896429 TI - Modeling conformational change in macromolecules as an elastic deformation. AB - Macromolecules are elastic bodies. Atomic structures are available for nucleic acids and proteins in two or more different conformations. It is a common practice to compare two structures by finding the best rigid body superposition of the molecules. This ignores possible deformations. There is useful information in the deviations from the rigid body superposition. If the deviations are considered to be elastic deformations of a common structure than it is possible to extract this information. Results are shown for comparisons of deoxyhemoglobin versus carbonmonoxyhemoglobin and for two different conformations of catabolite gene activator protein. PMID- 1896430 TI - The mutation beta 99 Asp-Tyr stabilizes Y--a new, composite quaternary state of human hemoglobin. AB - Carbonmonoxy hemoglobin Ypsilanti (beta 99 Asp-Tyr) exhibits a quaternary form distinctly different from any structures previously observed for human hemoglobins. The relative orientation of alpha beta dimers in the new quaternary form lies well outside the range of values observed for normal unliganded and liganded tetramers (Baldwin, J., Chothia, C., J. Mol. Biol. 129:175-220, 1979). Despite this large quaternary structural difference between carbonmonoxy hemoglobin Ypsilanti and the two canonical structures, the new quaternary structure's hydrogen bonding interactions in the "switch" region, and packing interactions in the "flexible joint" region, show noncovalent interactions characteristic of the alpha 1 beta 2 contacts of both unliganded and liganded normal hemoglobins. In contrast to both canonical structures, the beta 97 histidine residue in carbonmonoxy hemoglobin Ypsilanti is disengaged from quaternary packing interactions that are generally believed to enforce two-state behavior in ligand binding. These features of the new quaternary structure, denoted Y, may therefore be representative of quaternary states that occur transiently along pathways between the normal unliganded, T, and liganded, R, hemoglobin structures. PMID- 1896432 TI - Salivary lysozyme, lactoferrin and peroxidases: antibacterial effects on cariogenic bacteria and clinical applications in preventive dentistry. AB - Many antimicrobial agents in human saliva are known to have bacteriostatic or bactericidal effects on cariogenic bacteria, in particular against Streptococcus mutans. Studies have usually been conducted with purified agents (proteins) in vitro. Very little proof exists to show that they also affect oral cariogenic flora in vivo. Recent studies have shown that some salivary systems can act synergistically against Streptococcus mutans. Such synergistic antibacterial activity is likely to exist in the human mouth. Attempts to enhance the anticariogenic properties of saliva have been made by adding antimicrobial proteins such as peroxidase, lactoferrin and lysozyme to oral health products. Although clinical evidence is still limited, the idea of using such antimicrobial agents--"natural antibiotics"--rather than synthetic agents against cariogenic bacteria seems promising. PMID- 1896431 TI - The crystal structure of staphylococcal nuclease refined at 1.7 A resolution. AB - The crystal structure of staphylococcal nuclease has been determined to 1.7 A resolution with a final R-factor of 16.2% using stereochemically restrained Hendrickson-Konnert least-squares refinement. The structure reveals a number of conformational changes relative to the structure of the ternary complex of staphylococcal nuclease 1,2 bound with deoxythymidine-3',5'-diphosphate and Ca2+. Tyr-113 and Tyr-115, which pack against the nucleotide base in the nuclease complex, are rotated outward creating a more open binding pocket in the absence of nucleotide. The side chains of Ca2+ ligands Asp-21 and Asp-40 shift as does Glu-43, the proposed general base in the hydrolysis of the 5'-phosphodiester bond. The significance of some changes in the catalytic site is uncertain due to the intrusion of a symmetry related Lys-70 side chain which hydrogen bonds to both Asp-21 and Glu-43. The position of a flexible loop centered around residue 50 is altered, most likely due to conformational changes propagated from the Ca2+ site. The side chains of Arg-35, Lys-84, Tyr-85, and Arg-87, which hydrogen bond to the 3'- and 5'-phosphates of the nucleotide in the nuclease complex, are unchanged in conformation, with packing interactions with adjacent protein side chains sufficient to fix the geometry in the absence of ligand. The nuclease structure presented here, in combination with the stereochemically restrained refinement of the nuclease complex structure at 1.65 A, provides a wealth of structural information for the increasing number of studies using staphylococcal nuclease as a model system of protein structure and function. PMID- 1896433 TI - Remarks on the use of some basic epidemiological concepts in dentistry. AB - Scientific concepts do not emerge and develop in a vacuum but in the context in which they are used. Many concepts in epidemiology have their roots in destinal general infectious diseases that occur only once in one's life. The use of many epidemiological concepts varies greatly, even within medicine. Diseases such as dental caries, gingivitis and periodontitis cannot easily be described using concepts such as prevalence, incidence or risk, without creating confusion. The concepts sensitivity, specificity and positive and negative predictive value can also easily lead to misunderstandings. Clarifications regarding the use of these concepts in dentistry are suggested. PMID- 1896434 TI - Perspectives on xylitol-induced oral effects. AB - The review covered xylitol-induced effects on oral health. Xylitol was considered virtually nonacidogenic and to possess specific and unspecific advantageous effects on oral health. It was shown to mediate nonspecific remineralization, while its demineralization-inhibiting and S. mutans-reducing effects were regarded as specific. The clinical trials and field studies indicated that partial substitution of dietary sucrose by low doses of xylitol was associated with a pronounced caries reduction. PMID- 1896435 TI - Cartilage, function and craniofacial morphogenesis. AB - While primary cartilage of the craniofacial complex is a derivative of the chondroskeleton, secondary cartilage develops in close association with membrane bone. Mobile function, motility, is not always a prerequisite for the genesis of secondary cartilage but seems necessary for its maintenance as also, evidently, is mechanical load. Both primary and secondary cartilage have active morphogenetic potentials. For the primary cartilage this potential is essentially instrinsic, as has been demonstrated with transgenic mice, for instance. Consequently, primary cartilage is less adaptive to external influences than secondary cartilage. Analysis of the factors controlling the growth of the cartilaginous structures renders their utilization in reconstructive surgery more predictable. PMID- 1896436 TI - Genetic and epigenetic regulation of craniofacial development. AB - This paper reviews a series of odontometric, anthropometric and cephalometric investigations of genetic and epigenetic regulation of dental, occlusal and craniofacial development. The results show that genes encoded with the X and Y chromosomes regulate the development of tooth crowns and roots. The Y chromosome seems to affect general somatic growth by regulating both cell function and mitotic activity. The effects of the X chromosome seem to be more restricted and include influences on the growth of cartilaginous structures and dental enamel. The findings also indicate that high masticatory stress promotes jaw growth and decreases occlusal variation, supporting the hypothesis that masticatory activity regulates occlusal and craniofacial development. In addition, the findings suggest that nerve growth may affect bone growth in the craniofacial skeleton. PMID- 1896437 TI - In situ hybridization using single-stranded antisense RNA probes in oral pathology research. AB - In situ hybridization is a new molecular biological technique which has made it possible to demonstrate messenger RNA (mRNA) transcription of a specific gene in tissue sections and in cell preparations. In addition to the immunocytochemical methods widely used to locate gene products, e.g. a protein, nucleic acid hybridization techniques are having growing impact in pathological research. Increasing availability of cloned nucleotide sequences of human genes and the recent development of very sensitive and specific hybridization methods is rapidly expanding the field of gene function studies in cell and tumour biology. As with immunocytochemical techniques, hybridization techniques require proper controls for specificity. A basic knowledge of molecular biology is essential to determine the optimal conditions for successful hybridization and to interpret the results correctly. PMID- 1896438 TI - Multimodal radiography: a new imaging technique and system for oral diagnosis. AB - The multimodal radiography system is based on the combined use of narrow-beam radiography and spiral tomography in one set of equipment. The essentials of a system are a multifunction unit, preprogrammed imaging procedures for various dentomaxillofacial objects and a co-ordinate system for object location. Four years of clinical experience have shown that multimodal radiography is effective for depicting dentomaxillofacial structures for diagnostic purposes. The detailed narrow beam imaging mode of multimodal radiography has also been compared with intraoral radiography as regards their abilities to reveal periodontal and periapical lesions. Preliminary results indicate that detailed narrow beam radiography is more accurate than intraoral radiography in the diagnosis of periodontal and periapical pathology. PMID- 1896439 TI - Clinical aspects of oral implantology. AB - During the past few decades the use of implants in dentistry has increased markedly. Endosteal titanium implants are now most commonly used for replacement of single teeth and partial and full dentition. The success rates reported for osseointegrated implants depend on the type of implant and the criteria of success. Results are better for the mandible than the maxilla. Patient selection, careful planning of surgical and prosthetic treatment, and atraumatic, aseptic surgical procedures are essential for successful results. This article reviews various implant methods used in our Department and gives examples of treatment in particular clinical situations. PMID- 1896440 TI - Analyses of periodontal glycosaminoglycans and proteoglycans. Regulation by microbial, chemical and inflammatory factors. AB - During the last two decades one of the main lines of research in the Department of Periodontology in Turku has related to connective tissue glycosaminoglycans and proteoglycans. A general outline of current knowledge about proteoglycans is presented, with a review of most published and unpublished results on periodontal glycosaminoglycans and proteoglycans obtained in our Department. PMID- 1896442 TI - Are craniomandibular disorders a general health problem? AB - It has been suggested that the high prevalence of clinical signs and subjective symptoms of craniomandibular disorders (CMD) reported in many epidemiological studies mainly lie within the range of normal variation and do not indicate of a real health problem. However, other studies have shown an association between CMD and other disorders such as headache and neck pain. There also appears to be a marked association between sick leave and CMD. Successful occlusal treatment of CMD alleviates or eliminates signs and symptoms not associated with the primary diagnosis of CMD. The argument that CMD do not represent a real health problem is therefore unfounded. PMID- 1896441 TI - From contacts and bondings between bone and bioactive glass to bonding of bioactive glass and porcelain to metal alloys, different methods of fracture repair. AB - Bioactive glass has the ability to bond to bone. In this article the contact between glass and bone is discussed and the development of core alloy for an implant coated with bioactive glass and the oxidation of metal surface in ceramic fusion has been studied. Good bonding of coating materials to core alloys is necessary in dental implants. Using a pull test method we studied the bond strengths between various alloys and some composite materials clinically used to repair fractures of porcelain-veneered dental crowns. An experimental bioglass material was also studied. The bonding of composite materials to metal surfaces etched with hydrofluoric acid was almost as good as the bonding between metal and porcelain, or glass. PMID- 1896443 TI - Monomerization of RepA dimers by heat shock proteins activates binding to DNA replication origin. AB - DnaK is a major heat shock protein of Escherichia coli and the homolog of hsp70 in eukaryotes. We demonstrate the mechanism by which DnaK and another heat shock protein, DnaJ, render the plasmid P1 initiator RepA 100-fold more active for binding to the P1 origin of replication. Activation is the conversion of RepA dimers into monomers in an ATP-dependent reaction and the monomer form binds with high affinity to oriP1 DNA. Reversible chemical denaturants also convert RepA dimers to monomers and simultaneously activate oriP1 DNA binding. Increasing protein concentration converts monomers to dimers and deactivates RepA. Based on our data and previous work, we present a model for heat shock protein action under normal and stress conditions. PMID- 1896444 TI - Physiological and anatomical evidence for a magnocellular defect in developmental dyslexia. AB - Several behavioral studies have shown that developmental dyslexics do poorly in tests requiring rapid visual processing. In primates fast, low-contrast visual information is carried by the magnocellular subdivision of the visual pathway, and slow, high-contrast information is carried by the parvocellular division. In this study, we found that dyslexic subjects showed diminished visually evoked potentials to rapid, low-contrast stimuli but normal responses to slow or high contrast stimuli. The abnormalities in the dyslexic subjects' evoked potentials were consistent with a defect in the magnocellular pathway at the level of visual area 1 or earlier. We then compared the lateral geniculate nuclei from five dyslexic brains to five control brains and found abnormalities in the magnocellular, but not the parvocellular, layers. Studies using auditory and somatosensory tests have shown that dyslexics do poorly in these modalities only when the tests require rapid discriminations. We therefore hypothesize that many cortical systems are similarly divided into a fast and a slow subdivision and that dyslexia specifically affects the fast subdivisions. PMID- 1896445 TI - Assembly of combinatorial antibody libraries on phage surfaces: the gene III site. AB - A phagemid system was developed for the monovalent display of combinatorial antibody Fab libraries on the surface of filamentous phage M13. Fab fragments were fused to the carboxyl-terminal domain of the gene III protein. Phage displaying Fab fragments on their surface, or Phabs, were enriched by 10(3)- to 10(5)-fold on antigen-coated surfaces over nonspecific phage. The method may replace current antibody cloning techniques. PMID- 1896446 TI - Two-dimensional ordering of the DNA base guanine observed by scanning tunneling microscopy. AB - Guanine, one of the four DNA bases, has been observed by tunneling microscopy to form a two-dimensional ordered structure on two crystalline substrates, graphite and MoS2. The two-dimensional lattice formed by guanine is nearly identical on the two surfaces, and heteroepitaxy appears to be the growth mechanism in both cases. Although the resolution of molecular details is superior for the graphite substrate, the simpler results on MoS2 are not only easier to interpret but also facilitate the understanding of the more complex images on graphite. We propose that the interfacial structure is composed of linear chains of hydrogen-bonded molecules aligned into a closely packed two-dimensional array. PMID- 1896447 TI - A vaccinia virus double recombinant expressing the F and H genes of rinderpest virus protects cattle against rinderpest and causes no pock lesions. AB - Rinderpest is a highly contagious viral disease of ruminants with greater than 95% morbidity and mortality. We have constructed an infectious vaccinia virus recombinant that expresses both the fusion (F) gene and the hemagglutinin (H) gene of rinderpest virus. The Wyeth strain of vaccinia virus was used for the construction of the recombinant. Cattle vaccinated with the recombinant virus were 100% protected from challenge inoculation with greater than 1000 times the lethal dose of rinderpest virus. No transmission of recombinant vaccinia virus from vaccinated animals to contact animals was observed. The lyophilized form of vaccinia virus is thermostable and allows circumvention of the logistical problems associated with the distribution and administration of vaccines in the arid and hot regions of Asia and Africa. The insertional inactivation of both the thymidine kinase and the hemagglutinin genes of vaccinia virus led to increased attenuation of the virus; this was manifested by the lack of detectable pock lesions in vaccinated animals. This approach may have wide application in the development of safe and efficacious recombinant vaccines for humans and animals. This becomes quite relevant with the concern of the use of vaccinia virus in a population with high incidence of the human immunodeficiency virus. PMID- 1896448 TI - Replicational release of geminivirus genomes from tandemly repeated copies: evidence for rolling-circle replication of a plant viral DNA. AB - Agrobacterium-mediated inoculation of Nicotiana benthamiana plants with Ti plasmids containing tandem genome repeats derived from different strains of the gemini-virus beet curly top virus (BCTV) resulted in the production of unit length recombinant progeny genomes in systemically infected plants. When two putative plus-strand origins of replication were present in constructs used as inocula, a replicational escape mechanism was favored that resulted in progeny genomes of a single predominant genotype. The genotype was dependent upon the arrangement of repeated parental genomes in the inocula. Sequencing across the junction between parental BCTV strains in the recombinant progeny allowed mapping of the plus-strand origin of replication to a 20-base-pair sequence within the conserved hairpin found in all geminivirus genomes. In contrast, when inocula contained tandemly repeated BCTV genome sequences but only a single conserved hairpin, a number of different progeny genotypes were simultaneously replicated in infected plants, a result expected if unit-length viral genomes were generated by random intramolecular recombination events. These results and other considerations indicate that geminivirus DNA replication occurs by a rolling circle mechanism. PMID- 1896449 TI - Optimized strategies for sequence-tagged-site selection in genome mapping. AB - The physical mapping of complex genomes is based on the construction of a genomic library and the determination of the overlaps between the inserts of the mapping clones in order to generate an ordered, cloned representation of nearly all the sequences present in the target genome. Evaluation of the relative efficiency of experimental procedures used to accomplish this goal must minimally include a comparison of the fraction of the genome covered by the ordered arrays (or "contigs"), the average size of the contigs, and the cost, in terms of time and resources, required to generate the map. Sequence-tagged-site (STS) content mapping is one strategy that has been proposed and is being utilized for this type of experiment. This paper describes three STS selection schemes and presents computer simulations of contig-building experiments based on these procedures. The results of these simulations suggest that a nonrandom STS strategy that uses paired probes requires one-third to one-fourth as many STS assays as are required in random and nonpaired approaches, and also results in a map that has both greater genome coverage and a larger average contig size. This strategy promises to reduce the time and cost required to build a high-quality physical map. PMID- 1896450 TI - The initiator directs the assembly of a transcription factor IID-dependent transcription complex. AB - Highly purified RNA polymerase II was found to be able to weakly recognize the initiator (Inr) present in the adenovirus IVa2 and major late promoters. The association of RNA polymerase II with the Inr was enhanced by the general transcription factors. The Inr was capable of directing the formation of a DNA protein complex. Transcription competent complexes on the adenovirus major late and IVa2 promoters appear to be formed by alternative pathways mediated through the Inr and/or "TATA" motif. The presence of both motifs, however, is required for efficient transcription utilizing a discrete start site. Complexes formed at either site required transcription factor TFIID, the TATA binding protein. Consistent with this observation, a TFIID requirement was demonstrated for transcription from a mutant adenovirus major late promoter construct lacking a functional TATA motif. PMID- 1896451 TI - Dynamics, structure, and function are coupled in the mitochondrial matrix. AB - The coupling between molecular diffusion and the structure and function of the rat liver mitochondrial matrix was explored using fluorescence anisotropy techniques and electron microscopy. The results confirm that matrix ultrastructure and the concentration of matrix protein are influenced by the respiratory state of mitochondria and the osmolarity of the external medium. At physiological osmolarity, a fluorescent metabolite-sized probe was found to diffuse slowly in the mitochondrial matrix but not to be completely immobile. In addition, significant differences in diffusion rates were found to exist between different mitochondrial respiratory states, with the slowest diffusion occurring in states with the highest matrix protein concentration. These data support the concept of a matrix structure in which diffusion is considerably hindered due to limited probe-accessible water and further suggest that volume-dependent regulation of matrix protein packing may modulate metabolite diffusion and, in turn, mitochondrial metabolism. PMID- 1896452 TI - Molecular characterization of a region of DNA associated with mutations at the agouti locus in the mouse. AB - Molecular characterization of a radiation-induced agouti (a)-locus mutation has resulted in the isolation of a segment of DNA that maps at or near the a locus on chromosome 2 in the mouse. This region of DNA is deleted in several radiation- or chemical-induced homozygous-lethal a-locus mutations and is associated with specific DNA structural alterations in two viable a-locus mutations. We propose that DNA probes from this region of chromosome 2 will be useful for ultimately characterizing the individual gene or genes associated with a-locus function. PMID- 1896453 TI - Fidelity of targeted recombination in human fibroblasts and murine embryonic stem cells. AB - Targeted recombination in murine embryonic stem cells promises to be a powerful tool for introducing specific mutations into target genes to study development in mice and to create animal models of human disease. Gene targeting also holds potential for correcting genetic defects as an approach to human gene therapy. To precisely modify target genes, homologous recombination must proceed with high fidelity. However, several results have suggested that targeted recombination may be highly mutagenic. To test the accuracy of gene targeting we analyzed 44 independent targeted recombinants at the hypoxanthine phosphoribosyltransferase (HPRT) locus in a human fibroblast cell line and in mouse embryonic stem cells. We surveyed 80 kilobases around the sites of recombination by using chemical cleavage of mismatches. Only two mutations were found: a T----G transversion and a thymidine deletion. Thus, gene targeting in mammalian cells can be extremely accurate. These results demonstrate the feasibility of generating precise modifications of mammalian genomes by gene targeting. PMID- 1896454 TI - Two integrin-binding peptides abrogate T cell-mediated immune responses in vivo. AB - Two VLA proteins (or beta 1 integrins; originally called very late activation antigens) that bind to distinct determinants on fibronectin (FN) are increased on activated immune or memory T cells. VLA-4 binds to the peptide sequence Gly-Pro Glu-Ile-Leu-Asp-Val-Pro-Ser-Thr (GPEILDVPST in single-letter code) on the alternatively spliced CS-1 form of FN, whereas VLA-5 binds to an Arg-Gly-Asp sequence found on all forms of FN. It has been proposed that the migration of immune T cells out of blood vessels and through connective tissue to a site of antigenic challenge is facilitated by the interaction of such integrins with matrix protein molecules. We have examined directly the role of T-cell integrins in vivo by using the well-characterized, T-cell-mediated contact hypersensitivity (CHS) response to the hapten trinitrochlorobenzene (TNCB). We demonstrate that the cells that transfer CHS to TNCB adhere to FN in the presence of Ca2+/Mg2+, and T-cell populations depleted of FN-adherent cells do not transfer immunity. We further show that TNCB-immune T cells treated with the synthetic peptides GPEILDVPST or Gly-Arg-Gly-Asp-Ser-Pro (GRGDSP in single-letter code), ligands for VLA-4 and VLA-5, respectively, lose their ability to mediate this immune response in a murine model, whereas the control peptides Val-Ile-Pro-Asp-Leu-Thr-Glu-Ser Pro-Gly and Gly-Arg-Gly-Glu-Ser-Pro have no effect. Neither GPEILDVPST nor GRGDSP significantly inhibited the proliferative response of TNCB-immune T cells in vitro. These data suggest that FN-binding integrins on T cells play a role in the localization of T cells to sites of antigenic challenge in tissue. PMID- 1896455 TI - Stimulation of glycoprotein gp120 dissociation from the envelope glycoprotein complex of human immunodeficiency virus type 1 by soluble CD4 and CD4 peptide derivatives: implications for the role of the complementarity-determining region 3-like region in membrane fusion. AB - We have used a recombinant vaccinia virus vector encoding the envelope glycoprotein of human immunodeficiency virus type 1 to study receptor-induced structural changes related to membrane fusion. A truncated soluble form of human CD4 (sCD4) was found to stimulate dissociation of the external subunit (gp120) from the envelope glycoprotein complex of human immunodeficiency virus type 1 expressed at the cell surface. sCD4 stimulation of gp120 release was time- and concentration-dependent and was associated with specific binding of sCD4 to gp120. Synthetic peptide derivatives corresponding to residues 81-92 of human CD4 (overlapping the complementarity-determining region 3-like region) inhibited cell cell fusion mediated by the interaction between recombinant vaccinia-encoded CD4 and human immunodeficiency virus envelope glycoprotein. These peptide derivatives also stimulated gp120 release from the envelope glycoprotein complex. An analogous peptide derivative from chimpanzee CD4 (containing a single Glu----Gly substitution at the position corresponding to CD4 residue 87) was considerably less active at inhibition of cell-cell fusion and stimulation of gp120 release, consistent with the known inhibitory effect of this substitution on the ability of membrane-associated CD4 to mediate cell fusion. These results suggest that the sCD4-induced release of gp120 reflects postbinding structural changes in the envelope glycoprotein complex involved in membrane fusion, with the complementarity-determining region 3-like region playing a critical role. PMID- 1896456 TI - Tat-dependent adenosine-to-inosine modification of wild-type transactivation response RNA. AB - Tat is a potent activator of gene expression in human immunodeficiency virus type 1 (HIV-1). Activation by Tat requires a cis-acting element, the transactivation response (TAR) site, located in the viral long terminal repeat and the 5' end of all viral mRNAs. Sequences in TAR RNA can fold into a specific stem-loop structure, and certain features of the stem-loop are essential for Tat-mediated transactivation. In Xenopus oocytes, TAR sequences can inhibit the translation of 3' cis-linked mRNAs. However, coinjection of Tat and the TAR-containing RNA into oocyte nuclei relieves this translational inhibition [Braddock, M., Chambers, A., Wilson, W., Esnout, M. A., Adams, S.E. & Kingsman, S.M. (1989) Cell 58, 269-279]. We report here that the intramolecular TAR stem-loop structure is a substrate for the double-stranded RNA (dsRNA)-modifying activity, which converts adenosines to inosines. This activity is located in the nuclei of Xenopus oocytes. The specificity and extent of modification of adenosines in TAR is dependent on Tat. We propose that the dsRNA-modifying activity may be one of the cellular proteins that interacts with TAR in the nucleus. The possible role of TAR RNA modification in the expression of HIV-1 is discussed. PMID- 1896457 TI - Expression of human factor IX in rat capillary endothelial cells: toward somatic gene therapy for hemophilia B. AB - In aiming to develop a gene therapy approach for hemophilia B, we expressed and characterized human factor IX in rat capillary endothelial cells (CECs). Moloney murine leukemia virus-derived retrovirus vectors that contain human factor IX cDNA linked to heterologous promoters and the neomycin-resistant gene were constructed and employed to prepare recombinant retroviruses. Rat CECs and NIH 3T3 cells infected with these viruses were selected with the neomycin analogue, G418 sulfate, and tested for expression of factor IX. A construct with the factor IX cDNA under direct control by long terminal repeat gave the highest level of expression (0.84 and 3.6 micrograms per 10(6) cells per day for CECs and NIH 3T3 cells, respectively) as quantitated by immunoassays as well as clotting activity assays. A single RNA transcript of 4.4 kilobases predicted by the construct and a recombinant factor IX of 68 kilodaltons identical to purified plasma factor IX were found. The recombinant human factor IX produced showed full clotting activity, demonstrating that CECs have an efficient mechanism for posttranslational modifications, including gamma-carboxylation, essential for its biological activity. These results, in addition to other properties of the endothelium, including large number of cells, accessibility, and direct contact with the circulating blood, suggest that CECs can serve as an efficient drug delivery vehicle producing factor IX in a somatic gene therapy for hemophilia B. PMID- 1896458 TI - Histidine pKa shifts accompanying the inactivating Asp121----Asn substitution in a semisynthetic bovine pancreatic ribonuclease. AB - A semisynthetic RNase, RNase-(1-118).(111-124), consisting of a noncovalent complex between residues 1-118 of RNase (obtained from the proteolytic digestion of RNase A), and a synthetic 14-residue peptide containing residues 111-124 of RNase, exhibits 98% of the enzymatic activity of bovine pancreatic ribonuclease A (EC 3.1.27.5). The replacement of aspartic acid-121 by asparagine in this semisynthetic RNase to form the "D121N" analog reduces kcat/Km to 2.7% of the value for RNase A. In the present work, 1H NMR spectroscopy has been used to probe the ionization states of His12, His105, and His119 in this catalytically defective semisynthetic RNase. A comparison of the observed resonances of D121N with those previously determined by others for RNase A enabled us to assign the C2 proton NMR resonances to individual residues; the assignment of His119 was confirmed by titrating D121N with the fully deuterated peptide, [Asn121]-RNase (111-124). The observed pKa values of His12, His105, and His119 decrease 0.18, 0.16, and 0.02 pH unit, respectively, as a result of the D121N replacement. Values calculated by using a finite difference algorithm to solve the Poisson Boltzmann equation (the DELPHI program, version 3.0) and a refined 2.0-A coordinate set for the crystal structure of D121N differ significantly for active site residues His12 (delta pKa = -0.58) and His119 (delta pKa = -0.55) but not for His105 (delta pKa = -0.10). The elmination of bound water from the calculations reduced, but did not reconcile, these discrepancies (His12, delta pKa = -0.36; His119, delta pKa = -0.41). PMID- 1896459 TI - Evolution and relatedness in two aminoacyl-tRNA synthetase families. AB - Sequence segments of about 140 amino acids in length, each containing a selected consensus region, were used in alignments of the aminoacyl-tRNA synthetases with the aim of discerning their evolutionary relationships. In all cases tested, enzymes specific for the same amino acid from a variety of organisms grouped together, reinforcing the supposition that the aminoacyl-tRNA synthetases are very ancient enzymes that evolved to include the full complement of 20 amino acids long before the divergence leading to prokaryotes and eukaryotes. The enzymes are divided into two mutually exclusive groups that appear to have evolved from independent roots. Group I, for which two sequence segments were analyzed, contains the enzymes specific for glutamic acid, glutamine, tryptophan, tyrosine, valine, leucine, isoleucine, methionine, and arginine. Group II enzymes include those activating threonine, proline, serine, lysine, aspartic acid, asparagine, histidine, alanine, glycine, and phenylalanine. Both groups contain a spectrum of amino acid types, suggesting the possibility that each could have once supported an independent system for protein synthesis. Within each group, enzymes specific for chemically similar amino acids tend to cluster together, indicating that a major theme of synthetase evolution involved the adaptation of binding sites to accommodate related amino acids with subsequent specialization to a single amino acid. In a few cases, however, synthetases activating dissimilar amino acids are grouped together. PMID- 1896460 TI - Development of vivo of genetic variability of simian immunodeficiency virus. AB - Rapid development of genetic variability may contribute to the pathogenicity of lentiviruses as it may allow escape from immune surveillance and/or from suppression of virus replication. Although apathogenic in African green monkeys, simian immunodeficiency virus isolated from African green monkeys is shown to display extensive genetic variability and defectiveness in the V1- and V2-like variable domains of the external envelope protein comparable to that known for human immunodeficiency virus. However, in contrast to the situation in human immunodeficiency virus-infected individuals, a predominant major virus variant was detected neither in a monkey naturally infected for more than 10 years nor in two monkeys infected with a molecular virus clone for 15-20 months. Extensive variability evolves from a single genotype with a maximal rate of 7.7 mutations per 1000 nucleotides per year. A remarkable selection for nonsynonymous mutations that accounts for 92% of all changes indicates continuous selection of variants. PMID- 1896461 TI - C-terminal processing of barley alpha-amylase 1 in malt, aleurone protoplasts, and yeast. AB - C-terminal processing of low pI barley alpha-amylase (AMY1) results in multiple forms in malt, aleurone protoplasts, and transformed yeast. Expression of an AMY1 cDNA in yeast thus leads to four secreted forms with distinct pI values between 4.7 and 5.1 and essentially identical Mr. AMY1-1 and AMY1-2 lacking the C terminal Arg-Ser are generated by carboxypeptidase in vitro from AMY1-3 and AMY1 4, respectively. In vivo processing is due to the KEX1-encoded yeast carboxypeptidase. AMY1-2 and AMY1-4 are fully active, whereas AMY+-1 and AMY1-3 retain 3-4% activity toward p-nitrophenyl maltoheptaoside and have one fewer SH group, due to reaction with glutathione. AMY1-1-AMY1-4 are indistinguishable from malt AMY1 with respect to Ca(2+)-, substrate-, and beta-cyclodextrin-binding as well as recognition by three monoclonal antibodies and limited proteolysis by proteinase K. Transient AMY1 precursors present in barley aleurone protoplasts were trapped by addition of serine carboxypeptidase inhibitors, indicating that endogenous carboxypeptidase participates in the maturation of AMY1 during germination. Three pairs of precursor/mature AMY1 forms are recognized, presumably corresponding to the three genes encoding AMY1. Malt carboxypeptidase II can convert in vitro the precursors isolated from protoplasts into processed enzyme, and AMY1 from malt accordingly lacks the C-terminal heptapeptide. This report thus demonstrates posttranslational protein modification by carboxypeptidase in higher plants. PMID- 1896462 TI - Selection of motile nonchemotactic mutants of Escherichia coli by field-flow fractionation. AB - We have developed a chromatographic method for isolating bacterial cells that are motile but nonchemotactic. Separation of strains of different phenotype occurs along a thin horizontal channel between two stirred chambers, the lower one containing a chemical attractant. The channel is bounded above and below by rigid filters, permeable to the attractant but not to the bacteria. The lower part of the channel is occupied by a porous plate comprising a vertical array of capillary tubes. An aliquot of cells is injected at one end of the channel and eluted by continuous flow of cell-free medium. Fluid leaving the other end of the channel is collected in a fraction collector. Cells that respond to the gradient swim to the bottom of the channel where they are retarded by the capillary array. Nonmotile cells sink to the bottom and are trapped in a similar manner. Motile cells that fail to respond to the gradient diffuse across the full height of the channel and, thus, travel through the apparatus at the average velocity of the eluent. When mixed with wild-type cells at a ratio of 1:1000 and subjected to an aspartate gradient, aspartate-blind cells were recovered quantitatively. The enrichment was approximately 200 to 1. The wild-type cells that survived the selection had a poorly motile phenotype. PMID- 1896463 TI - Structure of human beta 1 beta 1 alcohol dehydrogenase: catalytic effects of non active-site substitutions. AB - The three-dimensional structure of human beta 1 beta 1 alcohol dehydrogenase (ADH; EC 1.1.1.1) complexed with NAD+ has been determined by x-ray crystallography to 3.0-A resolution. The amino acids directly involved in coenzyme binding are conserved between horse EE and human beta 1 beta 1 alcohol dehydrogenase in all but one case [serine (horse) vs. threonine (human) at position 48]. As a result, the coenzyme molecule is bound in a similar manner in the two enzymes. However, the strength of the interactions in the vicinity of the pyrophosphate bridge of NAD+ appears to be enhanced in the human enzyme. Side chain movements of Arg-47 and Asp-50 and a shift in the position of the helix comprising residues 202-212 may explain both the decreased Vmax and the decreased rate of NADH dissociation observed in the human enzyme vs. the horse enzyme. It appears that these catalytic differences are not due to substitutions of any amino acids directly involved in coenzyme binding but are the result of structural rearrangements resulting from multiple sequence differences between the two enzymes. PMID- 1896464 TI - Localization of stromelysin gene expression in atherosclerotic plaques by in situ hybridization. AB - The stromelysins are members of a family of extracellular matrix metalloproteinases. These enzymes may erode the connective tissue in atherosclerotic plaques, leading to fissuring and acute thrombotic events. Cell specific stromelysin expression in human atherosclerotic plaques was studied by in situ hybridization and immunocytochemistry. Sections were taken from nine coronary arteries: eight with well-established plaques and one normal. Unambiguous signals were seen in five plaques, two were inconclusive, and the remaining sample was negative, as was the normal coronary artery. Stromelysin mRNA transcripts were localized to isolated individual cells, some of which were smooth muscle, in the plaque cap, intima, and adventitia, but not the media. Expression was also seen in large clusters of macrophages that contained intracellular lipid deposits. The isolated expression of stromelysin by smooth muscle cells may reflect local connective tissue remodeling associated with growth and the formation of the plaque, whereas the more extensive expression associated with macrophages may be of greater pathological significance, contributing to the destabilization of the extracellular matrix and eventual plaque rupture. PMID- 1896465 TI - Measurement of ligand-receptor interactions. AB - One distinguishing feature of "life" is that the physical forces between biological molecules and membrane surfaces are often highly specific, in contrast to nonspecific interactions such as van der Waals, hydrophobic, and electrostatic (Coulombic) forces. We have used the surface-forces-apparatus technique to study the specific "lock and key" or "ligand-receptor" interaction between two model biomembrane surfaces in aqueous solution. The membranes were lipid bilayers supported on mica surfaces; one carrying streptavidin receptors, the other exposing biotin ligand groups. We found that, although no unusual or specific interaction occurs between two avidin or two biotin surfaces, an avidin and a biotin surface exhibit a very strong, very short-range (less than 1 nm) attraction and that the binding mechanism involves equally specific molecular rearrangements. The results also show that highly specific biological interactions such as are involved in immunological recognition and cell-cell contacts may be studied at the molecular level and in real time by the surface forces-apparatus technique. PMID- 1896466 TI - Assembly of the Escherichia coli 30S ribosomal subunit reveals protein-dependent folding of the 16S rRNA domains. AB - Protein-nucleic acid interactions involved in the assembly process of the Escherichia coli 30S ribosomal subunit were quantitatively analyzed by high resolution scanning transmission electron microscopy. The in vitro reconstituted ribonucleoprotein (core) particles were characterized by their morphology, mass, and radii of gyration. During the assembly of the 30S subunit, the 16S rRNA underwent significant conformational changes that were governed by the cooperative interactions of the ribosomal proteins. The sequential association of the first 12 proteins with the 16S rRNA resulted in the formation of core particles containing up to three mass centers at distinct stages of the assembly process. These globular mass centers may correspond to the three major domains (5', central, and 3') of the 16S rRNA. Through the subsequent interactions of the late assembly proteins with the 16S rRNA, two of the three domains merge, yielding the basic structural traits of the native 30S subunit. The fine morphological features of the native 30S subunit became distinctly resolved only after the addition of the full complement of proteins. The fully reconstituted 30S subunits are active in polyphenylalanine synthesis assays. Visualization of the assembly mechanism of the E. coli 30S ribosomal subunit revealed domain specific folding of the 16S rRNA through the formation of distinct intermediate core particles hitherto not observed. PMID- 1896468 TI - Chemical attraction of kleptoparasitic flies to heteropteran insects caught by orb-weaving spiders. AB - Insects of the heteropteran families Pentatomidae (stink bugs) and Coreidae (squash bugs), when being eaten by the orb-weaving spider Nephila clavipes, attract flies of the family Milichiidae. The flies aggregate on the bugs and, as kleptoparasites, share in the spider's meal. Stink bugs and squash bugs typically eject defensive sprays when attacked; they do so when caught by Nephila, but the spray only minimally affects the spider. Evidence is presented indicating that it is the spray of the bugs that attracts milichiids to the spider's catch. PMID- 1896467 TI - Primary structure of a human arginine-rich nuclear protein that colocalizes with spliceosome components. AB - The cDNA for a 54-kDa nuclear protein (p54) has been cloned from a human hepatoma expression library. Contained within p54 is an arginine/serine-rich region similar to segments of several proteins that participate in pre-mRNA splicing including the 70-kDa component of U1 small nuclear and "suppressor-of-white apricot" proteins. The arginine/serine-rich region is dominated by a series of 8 amino acid imperfect repetitive motifs (consensus sequence, Arg-Arg-Ser-Arg-Ser Arg-Ser-Arg). Antibodies raised against synthetic peptides of p54 react with an approximately 70-kDa protein on immunoblots of HeLa cell and rat liver nuclear proteins. This apparent discrepancy in mass is also observed when p54 mRNA is translated in vitro. Indirect immunofluorescence studies in HeLa cells show that p54 is distributed throughout the nucleus in a speckled pattern, with an additional diffuse labeling of the nucleus excluding the nucleoli. Double immunofluorescence experiments indicate that these punctate regions are coincident with the speckles seen in cells stained with antibodies against several constituents of the pre-mRNA splicing machinery. Sedimentation analysis of HeLa cell extracts on sucrose gradients showed that p54 migrates at 4-6 S, indicating that the protein is not a tightly associated component of snRNPs. Although the function of p54 is not yet known, our structure and immunolocalization data suggest that this protein may have a role in pre-mRNA processing. PMID- 1896469 TI - X chromosome-linked and mitochondrial gene control of Leber hereditary optic neuropathy: evidence from segregation analysis for dependence on X chromosome inactivation. AB - Leber hereditary optic neuropathy (LHON) has been shown to involve mutation(s) of mitochondrial DNA, yet there remain several confusing aspects of its inheritance not explained by mitochondrial inheritance alone, including male predominance, reduced penetrance, and a later age of onset in females. By extending segregation analysis methods to disorders that involve both a mitochondrial and a nuclear gene locus, we show that the available pedigree data for LHON are most consistent with a two-locus disorder, with one responsible gene being mitochondrial and the other nuclear and X chromosome-linked. Furthermore, we have been able to extend the two-locus analytic method and demonstrate that a proportion of affected females are likely heterozygous at the X chromosome-linked locus and are affected due to unfortunate X chromosome inactivation, thus providing an explanation for the later age of onset in females. The estimated penetrance for a heterozygous female is 0.11 +/- 0.02. The calculated frequency of the X chromosome-linked gene for LHON is 0.08. Among affected females, 60% are expected to be heterozygous, and the remainder are expected to be homozygous at the responsible X chromosome linked locus. PMID- 1896470 TI - Identification of a fungal cutinase promoter that is inducible by a plant signal via a phosphorylated trans-acting factor. AB - Plant cutin monomers trigger, and glucose suppresses, the expression of the cutinase gene of pathogenic fungi. To identify the cutinase promoter region responsible for induction by the unique plant components, a promoter analysis was done with transformants. Plasmids were constructed that contained (i) the 5' flanking region of the cutinase gene or its deletion mutants from Fusarium solani pisi fused with a chloramphenicol acetyltransferase (CAT) reporter gene and (ii) a constitutive promoter fused with a hygromycin phosphotransferase gene. Hygromycin-resistant transformants of F. solani pisi generated by electroporation were assayed for CAT activity inducible by cutin hydrolysate and for glucose repression of this induction. CAT was induced in a glucose-repressible manner when fused with a 360-base-pair (bp), or longer, segment of the 5' flanking region of the cutinase gene, and deletion of the next 135 bp abolished this induction. Gel retardation assays showed that a protein(s) in nuclear extract from the fungus bound to the 5' flanking region of cutinase gene, and this binding was also abolished when the same 135-bp segment was deleted. These results show that the -225 to -360 segment of the cutinase gene contains a cis acting regulatory element that binds trans-acting factor(s) in the nuclei. Treatment of the nuclear extract with immobilized phosphatase abolished binding to the promoter, suggesting that binding required a phosphorylated form of the protein. With isolated nuclei, phosphorylation of a protein occurred only in the presence of both cutin monomer and the fungal protein factor. The presence of protein kinase inhibitor H7 during the preincubation of nuclei with the monomer and protein factor inhibited cutinase gene transcription. These results suggest that cutin monomer causes phosphorylation of a transcription factor that binds to the -225 to -360 segment of the cutinase gene and enhances transcription of this gene. PMID- 1896471 TI - cDNA cloning of human R-type pyruvate kinase and identification of a single amino acid substitution (Thr384----Met) affecting enzymatic stability in a pyruvate kinase variant (PK Tokyo) associated with hereditary hemolytic anemia. AB - cDNA clones for human R-type pyruvate kinase (PK) were isolated from a human reticulocyte cDNA library, constructed by PCR with a single gene-specific primer. The full-length cDNA was 2060 base pairs long, and the cDNA encoded 574 amino acids, the same number as that by rat R-type PK. Compared with human L-type PK, R type PK was 31 amino acids longer at the amino terminus. We also cloned and characterized R-type PK cDNA clones from patients with hereditary hemolytic anemia from a PK deficiency, PK Tokyo. A single nucleotide substitution (ACG to ATG) was found at nucleotide 1151 of the coding sequence of the R-type PK, which caused an amino acid substitution, Thr384----Met. Dot blot hybridization of PCR amplified genomic DNA from patients and their parents by allele-specific oligonucleotide probes showed that the parents, who were second cousins, were heterozygous. To confirm that the nucleotide change was responsible for the variant phenotype, we expressed the L-type PK with the single amino acid change in Escherichia coli and characterized the enzyme. The variant PK was thermolabile and moved slowly in the polyacrylamide gel buffered in 10 mM Tris.HCl, pH 8.3; these characteristics were fully compatible with data obtained from the patient's PK. From these results, we concluded that enzymatic stability of the variant was affected by the point mutation of the PK-encoding gene. PMID- 1896473 TI - Evidence that a triplex-forming oligodeoxyribonucleotide binds to the c-myc promoter in HeLa cells, thereby reducing c-myc mRNA levels. AB - A synthetic 27-base-long oligodeoxyribonucleotide, termed PU1, has been shown to bind to duplex DNA to form a triplex at a single site within the human c-myc P1 promoter. PU1 has been administered to HeLa cells in culture to examine the feasibility of influencing transcription of the c-myc gene in vivo. It is shown that uptake of PU1 into the nucleus of HeLa cells is efficient and that the compound remains intact for at least 4 hr. In nuclei extracted from PU1-treated cells, inhibition of DNase I cleavage is detected within the c-myc P1 promoter at the target site for triplex formation. The inhibition is shown to be both site and oligodeoxyribonucleotide specific. After cellular uptake of PU1, it is shown that steady-state mRNA arising from the c-myc P1 initiation site is selectively reduced relative to total mRNA, relative to mRNA from the alternative c-myc P2 initiation site, and relative to mRNA derived from the beta-actin promoter. Significant mRNA repression is not seen upon treating cells with oligodeoxyribonucleotides that fail to bind to the P1 promoter target. Taken together, these data suggest that triplex formation can occur between an exogenous oligodeoxyribonucleotide and duplex DNA in the nucleus of treated cells. PMID- 1896472 TI - Ferritin gene transcription is regulated by iron in soybean cell cultures. AB - Iron-regulated ferritin synthesis in animals is dominated by translational control of stored mRNA; iron-induced transcription of ferritin genes, when it occurs, changes the subunit composition of ferritin mRNA and protein and is coupled to translational control. Ferritins in plants and animals have evolved from a common progenitor, based on the similarity of protein sequence; however, sequence divergence occurs in the C termini; structure prediction suggests that plant ferritin has the E-helix, which, in horse ferritin, forms a large channel at the tetrameric interface. In contemporary plants, a transit peptide is encoded by ferritin mRNA to target the protein to plastids. Iron-regulated synthesis of ferritin in plants and animals appears to be very different since the 50- to 60 fold increases of ferritin protein, previously observed to be induced by iron in cultured soybean cells, is accompanied by an equivalent accumulation of hybridizable ferritin mRNA and by increased transcription of ferritin genes. Ferritin mRNA from iron-induced cells and the constitutive ferritin mRNA from soybean hypocotyls are identical. The iron-induced protein is translocated normally to plastids. Differences in animal ferritin structure coincide with the various iron storage functions (reserve for iron proteins and detoxification). In contrast, the constancy of structure of soybean ferritin, iron-induced and constitutive, coupled with the potential for vacuolar storage of excess iron in plants suggest that rapid synthesis of ferritin from a stored ferritin mRNA may not be needed in plants for detoxification of iron. PMID- 1896474 TI - Gene- and strand-specific repair in vitro: partial purification of a transcription-repair coupling factor. AB - In eukaryotic and prokaryotic cells, activity transcribed genes and, in some instances, the template strand of these genes have been found to be repaired 2-10 times more rapidly than nontranscribed genes or the coding strand of transcribed genes. We demonstrate here gene- and template strand-specific repair synthesis in vitro by using an Escherichia coli cell-free extract and a plasmid carrying a gene with the strong tac promoter. Strand-specific repair of UV, 4' hydroxymethyl1-4,5',8-trimethylpsoralen, and cis-dicholorodiammine platinum(II) damage was dependent upon transcription and a functional nucleotide excision repair system and was stimulated by 6% (wt/vol) polyethylene glycol. A defined system consisting of the transcription and repair proteins in highly purified form did not perform strand-specific repair; however, active fractions of extract conferred strand specificity to the defined system. Transcription-repair coupling activity was partially purified from extract by successive DEAE-agarose and gel filtration chromatography. The coupling factor is heat-labile, with an estimated Mr of 100,000. PMID- 1896475 TI - Rapid renaturation of complementary DNA strands mediated by cationic detergents: a role for high-probability binding domains in enhancing the kinetics of molecular assembly processes. AB - The rate of renaturation for complementary DNA strands can be enhanced greater than 10(4)-fold by the addition of simple cationic detergents, and the reaction is qualitatively and quantitatively very similar to that found with purified heterogeneous nuclear ribonucleoprotein A1 protein. Under optimal conditions, renaturation rates are greater than 2000-fold faster than reactions run in 1 M NaCl at 68 degrees C. The reaction is second-order with respect to DNA concentration, and reaction rates approach or equal the rate with which complementary strands are expected to encounter each other in solution. Renaturation can even be observed well above the expected melting temperature of the duplex DNA, demonstrating that some cationic detergents have DNA double-helix stabilizing properties. The reaction is also extremely rapid in the presence of up to a 10(6)-fold excess of noncomplementary sequences, establishing that renaturation is specific and relatively independent of heterologous DNA. This finding also implies that up to several thousand potential target sequences can be sampled per strand per second. Such reagents may be useful for procedures that require rapid nucleic acid renaturation, and these results suggest ways to identify and design other compounds that increase the kinetics of association reactions. Moreover, this work provides further support for a model relating the existence of flexible, weakly interacting, repeating domains to their function in rapid molecular assembly processes in vitro and in vivo. PMID- 1896477 TI - [The effect of disease on pharmacokinetics of drugs. 1. Kidney diseases]. PMID- 1896478 TI - [The solubility kinetics of enteric-resistant tablets using riboflavin test tablets. 6. Pharmaceutic-technologic and analytic studies on gastric juice resistant dosage forms]. AB - To examine the dissolution kinetics of enteric coatings in vivo a test system with riboflavine was developed. This system allows to realize the beginning of disintegration in the small gut because riboflavine is excreted in urine already within 1 h after ingestion, and to locate the area of dissolution of the tablet in vivo, because riboflavine absorption is reduced in the great gut and colon. Thus the test system allows to examine and improve coating compositions in vivo and to demonstrate changes of drug dissolution in vivo conditioned by storage of enteric coated pharmaceuticals. PMID- 1896476 TI - Lateral redistribution of cytochrome b6/f complexes along thylakoid membranes upon state transitions. AB - The cytochrome b6/f complex operates in photosynthetic electron transfer either in linear electron flow from photosystem II to photosystem I or in cyclic flow around photosystem I. Using membrane fractionation and immunocytochemistry, we show a change in lateral distribution of cytochrome b6/f complexes along the thylakoid membranes during state transitions. This change is seen in maize as well as in the green algae Chlamydomonas reinhardtii. When either of the two organisms were adapted to state II in vivo, the proportion of cytochrome b6/f complexes found in the photosystem I-enriched stroma lamellae regions was significantly larger than after adaptation to state I. A similar observation was made upon state I to state II transitions done in vitro by illuminating, in the presence of ATP, broken maize chloroplasts prepared from dark-adapted leaves. This reorganization of the electron-transfer chain is concurrent with the change in light-energy distribution between the two photosystems, which requires lateral displacement of light-harvesting complex II. That the changes in lateral distribution of both cytochrome b6/f and light-harvesting II complexes seen upon state transition in vitro similarly required addition of exogenous ATP, suggests that the change in cytochrome b6/f organization also depends on kinase activity. The increased concentration of cytochrome b6/f complexes in the vicinity of photosystem I in state II is discussed in terms of an increase in cyclic electron flow, thus favoring ATP production. Because transition to state II can be triggered in vivo by ATP depletion, we conclude that state transitions should be regarded not only as a light-adaptation mechanism but also as a rerouting of photosynthetic electron flow, enabling photosynthetic organisms to adapt to changes in the cell demand for ATP. PMID- 1896479 TI - Determination of oxprenolol and its glucuronide metabolite in plasma and urine using high-performance liquid chromatography. AB - A HPLC assay is presented for the determination of oxprenolol (1) and its glucuronic acid conjugate (2) in human plasma and urine. The procedure employs a selective re-extraction using alprenolol (3) as the internal standard, followed by reversed-phase chromatography and UV-detection. The minimal detectable concentration is 10 ng/ml in plasma and 50 ng/ml in urine, using 1.0 and 0.5 ml of plasma and urine, respectively. Within-run and day-to-day variations are below 10% at all concentrations examined. Plasma and urine samples of either healthy volunteers or patients with renal failure are free of interferences from endogenous compounds and drugs frequently used in these patients. The glucuronic acid conjugate of oxprenolol is determined as the parent compound after hydrolytic cleavage with beta-glucuronidase/arylsulfatase. The specificity and selectivity of this cleavage are also demonstrated. PMID- 1896480 TI - Screening of Candida sp. for N-dealkylation of codeine. AB - A number of Candida species were selected in order to test their ability to N- or O-demethylate codeine. Complex media and chemically defined media used in our experiments. Transformation products were analysed by reversed phase HPLC and TLC methods. N- and O-demethylation of codeine was performed by C. tropicalis NCYC 997, NCYC 405, NCYC 470 and C. albicans LSHTM 3153. Transformation by C. tropicalis NCYC 997 had better results. N- and O-demethylation occurred in the chemically defined medium. Change in the colour of the transformation mixture, in cultures containing more than 5 mmol.l-1 codeine, was attributed to codeine N oxide, but its presence was not confirmed by HPLC. N- and O-demethylation of codeine by Candida sp. was compared to that occurred in mammals. PMID- 1896481 TI - [Homologs of 2-acetamino-4-nitropropoxybenzene (Falimint). 2. Metabolism of homologs]. PMID- 1896482 TI - [The anticonvulsant action of (+)- and (-)-tranylcypromine]. PMID- 1896483 TI - [The action of piracetam, meclofenoxate and vinpocetine in comparative disease models in mice]. PMID- 1896484 TI - [The biochemical basis of pharmaceutical chemistry. 10. Enzymes and enzyme inhibitors as drugs]. PMID- 1896485 TI - Neuropeptides related to [Arg8]vasopressin facilitates social recognition in rats. AB - The decrease of social investigations of adult rats during a second encounter session with the same juvenile was used as an index of social recognition or memory. Social recognition was present when the interexposure interval was 15 or 30 min, but not when this interval lasted 60 or 120 min. Animals treated with desglycinamide[Arg8]vasopressin (DGAVP) (6.0 micrograms.kg-1, SC) or [pGlu4,Cyt6]AVP-(4-8) (AVP-(4-8] (1.0 microgram.kg-1, SC), immediately after the first encounter, recognized the same juveniles still after 120 min, suggesting a facilitatory effect of these peptides on social recognition and that this effect of vasopressin is dissociated from the classical endocrine effects of this hormone. The decrease of social investigating behavior, in both placebo- and DGAVP-treated rats, was completely due to a decrease in anogenital exploration, indicating that the social recognition in rats is presumably based on odor cues from the anogenital part of the body. PMID- 1896486 TI - Weight loss and sweetness preferences: the effects of recent versus past weight loss. AB - The present study examined the effects of weight loss, recent and past, on perceptions of pleasantness and sweetness intensity of sucrose solutions. Subjects high or low in current weight loss, and high or low in past weight loss (weight suppression) rated sucrose solutions before and after the ingestion of a glucose solution. Current weight loss was total weight loss over the 3 months prior to the study; past weight loss was defined in terms of the difference between maximal and current weight. Subjects were 40 women, all of whom reported that they were dieting. After a 12-hour overnight fast, each subject tasted and rated five concentrations of sucrose solutions (2.5, 5.0, 10.0, 20.0, and 40.0) for pleasantness and sweetness. High weight suppressors rated the sucrose solutions, before and after the glucose load, as significantly less pleasant than did low weight suppressors. High recent weight losers rated the sucrose solutions as significantly more pleasant than did low current weight losers following, but not prior to, the glucose load. These results were inconsistent with setpoint theory. High weight suppressors did not show an increase in sweetness preference as predicted by this theory. It was suggested that while weight loss affects taste hedonics, the nature of this relationship depends on the recency of the weight loss. PMID- 1896487 TI - Sympathoadrenal effects on extinction of rewarded running in the rat. AB - Two groups of rats underwent adrenal demedullation or sham surgery before being trained to run in a straight runaway for food reward at a short intertrial interval (90 s). Half of each group of animals were then injected IP with the sympathetic neurotoxin, 6-hydroxydopamine HBr (6-OHDA; 30 mg/kg); the remainder received saline vehicle. After 3 more days of acquisition training, running was extinguished over 12 trials in all rats. Running times were similar in all groups at the start of extinction. In saline-injected animals, extinction proceeded more slowly in the demedullated than in the sham-operated group, but this effect was largely abolished by 6-OHDA. Consistent with previous results, there was evidence that 6-OHDA facilitated extinction, irrespective of adrenal demedullation, but this effect was most apparent in the time taken to emerge from the start-box. The rats were killed two days after the end of the experiment; cardiac noradrenaline levels were depleted by 83% of control values in 6-OHDA-treated animals. The results suggest that the adrenal medulla and sympathetic neurones have opposing and interacting effects on the response to nonreward. PMID- 1896488 TI - Sucrose to polycose preference shifts in rats: the role of taste, osmolality and the fructose moiety. AB - Rats given continuous access to 32% sucrose and Polycose solutions initially preferred sucrose but over days reversed their preference and drank more Polycose than sucrose. The role of taste and postingestive factors in this preference shift were investigated in several experiments. A strong and persistent preference for saccharin-sweetened Polycose over unsweetened Polycose was eliminated by intervening experience with a sucrose vs. Polycose choice test, suggesting that the postingestive effects modify the attractiveness of sweet taste. Osmolality differences between sucrose and Polycose were ruled out as an important factor; increasing the osmolality of Polycose by addition of glucose did not prevent the sucrose to Polycose preference shift. Rather, the shift in preference appears to result from some postingestive consequence of the fructose moiety contained in sucrose. This is indicated by the findings that rats did not reliably prefer a fructose-Polycose mixture to a sucrose solution in long-term tests, but developed preferences for maltose over sucrose solutions, and for glucose + Polycose over fructose + Polycose mixtures. Also, a 32% glucose solution was strongly preferred to a 32% fructose solution. Other studies examined the parameters of the sucrose to Polycose preference shift. The Polycose preference was accomplished by increases in both Polycose meal size and frequency. It occurred only with relatively concentrated solutions (16 and 32%) and was incomplete when the carbohydrates were presented in powdered form. Preexposure to Polycose enhanced the preference shift, whereas preexposure to sucrose retarded the development of the preference, suggesting that the shift occurs because Polycose is more rewarding, rather than because sucrose is more aversive. Polycose preference was lost after several days without the solutions but redeveloped in subsequent sucrose vs. Polycose choice tests. Thus the preference shift appears to be due to taste-postingestive consequence conditioning but its expression is dependent upon the nutritional state of the animal. PMID- 1896489 TI - Effects of maternal stress on puberty, fertility and aggressive behavior of female mice from different intrauterine positions. AB - We examined the effects of maternal stress (bright light and heat) during the last third of pregnancy on subsequent reproductive and behavioral characteristics of female mice from different intrauterine positions. Female mice that develop in utero between two male fetuses (2M females) differ from females that develop between two female fetuses (0M females) in their serum concentrations of both testosterone and estradiol during the fetal period of sexual differentiation. After birth, 0M and 2M females differ in a wide range of reproductive characteristics. We examined the effects of maternal stress on the response to social cues regulating the timing of first vaginal estrus and the length of the first postpubertal estrous cycle when 4 0M or 4 2M females were housed together next to an adult male. Maternal stress decreased the inhibitory effect of being housed with other females in terms of the length of the first postpubertal estrous cycle, but this only occurred in 0M females. We found no effect of maternal stress or intrauterine position on the capacity to mate and remain pregnant, regardless of whether 0M or 2M females were stressed or not stressed during early pregnancy prior to implantation. While there was no effect of prior intrauterine position on interfemale aggression or behavior toward young, maternal stress did tend to reduce the likelihood that females (in diestrus) would exhibit aggression toward other females. PMID- 1896490 TI - Interactions between body temperature and wheel running over the estrous cycle in rats. AB - Female rats were housed in Wahmann wheels under a 12:12 light-dark (LD) photoperiod for 36 days and then were switched to LD 10:14 for 36-64 days. Running was 95-100% nocturnal. Overall amounts of running were higher in LD 12:12, but changes over the estrous cycle were similar. On the night of proestrus running increased by 64% in LD 12:12 and 123% in LD 10:14 (p less than 0.0001) compared to the first night of diestrus. Nighttime Tb's were correlated with running levels. In LD 12:12 Tb on proestrus was higher by 0.3 +/- 0.0 degrees C (p less than 0.0001); in LD 10:14 it was higher by 0.2 +/- 0.0 degrees C (p less than 0.001) compared to diestrus-1. During L, Tb was lowest on proestrus and highest on estrus. Half of the rats exhibited a consistent phase advance of at least 30 min in both Tb and activity on proestrus. The advanced Tb acrophase was correlated with both the activity acrophase (r = .91; p less than 0.0001) and the amount of running (r = .60; p less than 0.01). The wheels of 6 rats were then locked at night in LD 10:14. There were no significant Tb changes from diestrus-1 across the cycle. However, Tb acrophase was delayed a mean of 76 +/- 16 min (p less than 0.01) in these rats. Also, the Tb acrophase across all days of the estrous cycle was delayed by 94 +/- 18 min (p less than 0.001) compared to when the wheels were open.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1896491 TI - Effects of chlordiazepoxide and putative anxiogenics on conditioned suppression in rats. AB - This paper reports two experiments. In Experiment 1, the effects of chlordiazepoxide alone and in combination with a series of putative antagonists at various sites on the GABA/benzodiazepine receptor complex on conditioned suppression of operant behavior in rats were assessed. Response rates during presentation of a stimulus associated with shock (CS responding) and when only positive reinforcement is effective (pre-CS responding) were analysed. Chlordiazepoxide (10 mg/kg) significantly increased CS responding. This effect was significantly antagonised by Ro15-1788 (10 mg/kg) and by picrotoxin (1.5 mg/kg), but not by bicuculline (1.5 mg/kg) or by delta-amino-n-valeric acid (10 or 20 mg/kg). Chlordiazepoxide also significantly, albeit more slightly, increased pre-CS responding and none of the other drugs tested significantly antagonised this action, though Ro15-1788 plus chlordiazepoxide resulted in pre CS response rates not significantly different from either chlordiazepoxide alone or control. These interactions are discussed in the context of the proposed GABA/benzodiazepine receptor complex with the conclusion that drug effects at the benzodiazepine- and picrotoxin-sensitive channel sites have an important role in mediating anxiolytic action. However, behavioral evidence of an important role for GABAa or GABAb receptors remains very limited. The second experiment studied the intrinsic actions of bicuculline, picrotoxin, and Ro15-1788 on conditioned suppression. Responding during a conditioned stimulus associated with a mild (0.125 to 0.15 mA) electric shock (CS responding) and a control rate of responding (pre-CS responding) were recorded. Bicuculline (1.5 mg/kg) and Ro15 1788 (10 mg/kg) did not significantly affect either response rate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1896492 TI - "Isolation stress" revisited: isolation-rearing effects depend on animal care methods. AB - Early reports of enhanced behavioral reactivity in isolation-reared rats attributed this syndrome to "isolation stress." In the studies reported here, this "isolation stress syndrome" was reliably obtained in adult rats reared from weaning in individual hanging metal cages. Such isolates showed behavioral and adrenocortical symptoms of profound fear during open-field testing, unlike group housed controls or littermate isolates reared singly in plastic cages. Animals in hanging metal cages are never touched by human caretakers, whereas rats reared in plastic cages are picked up and put in clean cages twice weekly. Handling hanging cage isolates twice weekly to model the handling associated with cage changes completely protected against this syndrome. Further, there was no hormonal, neurochemical or anatomical evidence of chronic stress even in hanging-cage isolates. Littermates housed in social groupings (three rats per plastic cage) also froze and defecated in the open field at rates comparable to hanging-cage isolates if they were the first animals to be tested from their social group cage. It is probable that odor cues from familiar cagemates in the open field protected socially reared animals tested subsequently from the same cage from this syndrome. It is concluded that isolates are not chronically stressed, and that rearing effects are the result of a complex interaction between prior handling, social experience and test conditions. PMID- 1896493 TI - Peripheral p-chloroamphetamine is an unsuitable probe for investigation of central serotoninergic control on renal renin secretion in the rat. AB - Intraperitoneal application of p-chloroamphetamine (PCA) is considered a suitable probe for investigation of central serotoninergic control on renin release in the rat, although it causes several behavioral and autonomic changes including negative water balance (increased urination and loss of body weight). The possibility that PCA-induced renin release is secondary to the alterations in water balance was investigated 1 hour after intraperitoneal PCA in male Wistar (Wi) (Experiment I). Long-Evans (LE) and diabetes insipidus (DI) (Experiment II), DI rats pretreated by the inhibitor of angiotensin I-converting enzyme captopril (Experiment III), and water-loaded or propranolol-pretreated Wi rats (Experiment IV). PCA treatment induced significant body weight loss, increase in hematocrit, stimulation of renin-aldosterone system (RAS) and elevation of plasma creatinine level. A toxic damage of the kidney and liver was documented histologically 72 h after 5 mg/kg PCA in Wi rats. The blockade of PCA-induced stimulation of RAS (by captopril or propranolol) markedly potentiated the attendant negative water balance, whereas positive water balance (oral water load) abolished PCA-induced renin secretion. In conclusion, intraperitoneal PCA is an unsuitable probe for investigation of central serotoninergic control on renin release in the rat since PCA-induced renin release is caused by the attendant negative water balance. PMID- 1896494 TI - Increased intake of water and NaCl solutions in omega-3 fatty acid deficient monkeys. AB - We previously reported that long-term omega-3 fatty acid deficiency is associated with increased water intake in rhesus monkeys. To determine whether the increase was specific to water, intakes of salt solutions were measured in 15-minute single-bottle tests. Deficient monkeys drank at least twice as much of all NaCl concentrations as controls. Overall intake decreased as salt concentration increased. In 2-bottle preference tests, deficient monkeys again drank more total fluid but neither preferred nor avoided normal saline compared to controls. When deprived of water, deficient monkeys concentrated urine as well as controls, demonstrating that the increased intake was not a result of renal failure or diabetes insipidus. Omega-3 fatty acids have roles both in neural membrane function and in metabolism of prostaglandins and other eicosanoids. Omega-3 fatty acid deficiency may affect drinking through changes in one or both of these functions. PMID- 1896495 TI - Tetrahydroaminoacridine alleviates medial septal lesion-induced and age-related spatial reference but not working memory deficits. AB - This study examined the effects of tetrahydroaminoacridine (THA, an anticholinesterase) on water-maze (WM) spatial reference (stable platform location during training) and spatial working memory (reversal of platform location) learning in young intact/medial septal (MS)-lesioned and aged rats. THA (1 or 3 mg/kg, IP) had no effect on reference or working memory performance of young intact rats. MS lesions decreased cholineacetyltransferase activity in the hippocampus and also impaired spatial reference and working memory. THA at 3 mg/kg stabilized MS lesion-induced reference memory performance deficit (path length increase), but was ineffective at 1 mg/kg. THA had no effect on the working memory performance of MS-lesioned rats. Aged rats were impaired in spatial reference and working memory tasks. THA at 3 mg/kg partially stabilized the age-induced spatial reference memory deficits, but was ineffective at 1 mg/kg. THA at either 1 or 3 mg/kg did not alleviate the age-related deficit in the working memory version of WM. The present results suggest that some of the age-related WM deficits may be related to the degeneration of the MS-hippocampus cholinergic system and that THA may be effective in stabilizing the reference memory deficits induced by hippocampal cholinergic dysfunction. PMID- 1896496 TI - Stress hyperthermia: physiological arguments that it is a fever. AB - The theory that stress (or emotional) rise in central temperature (Tc) in rats is a fever with an upward shift of the set-point temperature was tested with three experiments: 1) Measurement of tail skin temperature and Tc during the emotional Tc rise; 2) Investigation of the effect of ambient temperature on the emotional Tc rise; and 3) The assessment of emotional Tc rise during daytime and nighttime. Skin vasomotor responses helped the increase of Tc toward a higher level and contributed to the regulation of central temperature at this new higher level. The cold environment did not diminish the emotional rise of central temperature as it would be expected in the case of a hyperthermia. However, at night emotional fever reached a higher level than during the daytime, suggesting that prostaglandin rise in Tc is distinct from emotional or stress-induced hyperthermia. In conclusion, the experiments reported here confirm the hypothesis that the rise of Tc induced by handling or disturbance of the rats is regulated, and is due to a shift of the set-point as occurs in fever. PMID- 1896498 TI - Caffeine and novelty: effects on electrodermal activity and performance. AB - Caffeine has been shown to affect both physiological functioning and certain aspects of performance. These effects are typically attributed to a simple increase in general arousal. The present study was based on the theory that the effects of caffeine are actually multidimensional. Specifically, we hypothesized that the drug raises arousal, acts to maintain elevated arousal under conditions otherwise conductive to habituation, and enhances the impact of situational and psychological sources of arousal. Subjects were given caffeine (300 mg) or placebo and white noise or no noise and exposed to a series of pure tones and two Backwards Recall Tasks, one novel, the other repetitive. Electrodermal activity (EDA) and task performance were recorded. Caffeine increased arousal as measured by EDA. It also acted to slow habituation during repetitive stimulation, thus maintaining heightened arousal. Finally, it enhanced the effects of novel stimulation, which also independently raised arousal. These results support a multidimensional theory of caffeine effects and provide some understanding of the popularity of caffeine as a psychotropic agent. PMID- 1896497 TI - Effects of stimulus intensity and quality on discrimination of odorant mixtures by spiny lobsters in an associative learning paradigm. AB - The Florida spiny lobster, Panulirus argus, can behaviorally discriminate between members of a set of four artificial odorant mixture types: crab, mullet, oyster, and shrimp. The present experiments were designed to examine the effects of both intensity and quality on discrimination of odorant mixtures. This was accomplished by conditioning lobsters to only one concentration (0.5 mM) of shrimp mixture and testing them with four concentrations (0.005, 0.05, 0.5 and 5.0 mM) of shrimp mixture and two concentrations (0.05 and 0.5 mM) of oyster mixture. For the two appetitive behaviors examined, lobsters did not discriminate the conditioned mixture (0.5 mM shrimp) from any other of the same-type nonconditioned mixtures. For a third behavior, active avoidance, lobsters discriminated, to a significant degree, the 0.5 mM shrimp mixture from all of the nonconditioned mixtures. However, aversion values for the nonconditioned shrimp mixtures were markedly and consistently higher than those for the nonconditioned oyster mixtures for all three behaviors. Thus, when spiny lobsters are forced to use intensity as a cue (as in an aversive conditioning situation), they have the ability to discriminate between mixtures of the same quality but different intensity. Nevertheless, based on examination of post-conditioning decreases in appetitive behaviors, it is most likely that the intensity of an odorant mixture has a relatively minor effect on the discrimination of the quality of that mixture by these animals, at least over a 1000-fold concentration range. PMID- 1896499 TI - Castration alters susceptibility of male rats to specific seizures. AB - Studies in female rats indicate that estrogen reduction has both pro- and anticonvulsant effects on seizures, but that the respective effects are limited to specific types of seizures at selected doses of picrotoxin. This study was conducted to see if testosterone reduction had parallel effects on seizure susceptibility in males. Male rats were given castration or sham operations and allowed 3 weeks to recover. The latencies to myoclonic, focal, akinetic, and generalized tonic-clonic (GTC) seizures were scored in independent groups of sham operated or castrated males after injection with picrotoxin (3.5-7.5 mg/kg). The results showed that castrated males had significantly shorter latencies to GTC seizures than sham-operated males at the 3.5 mg/kg and 5.5 mg/kg doses of picrotoxin. There were no significant differences in the latencies to myoclonic, focal, or akinetic seizures between the two surgical groups. The findings suggest that, unlike endogenous estrogen, endogenous testosterone exerts only an anticonvulsant effect and that the effect is limited to GTC seizures. PMID- 1896500 TI - Enterostatin (Val-Pro-Asp-Pro-Arg), the activation peptide of procolipase, selectively reduces fat intake. AB - Valine-proline-aspartate-proline-arginine (VPDPR), the amino terminal pentapeptide of pancreatic procolipase, produced a dose-dependent reduction in food intake when injected intraperitoneally into Osborne-Mendel rats that had been starved overnight. This inhibition of feeding was observed when the rats were fed a high-fat diet but not in rats fed a high-carbohydrate, low-fat diet. At higher doses of VPDPR, the inhibition of feeding was maintained for over 6 hours. An equimolar mixture of the free amino acids had no effect on food intake. In rats adapted to a three-choice macronutrient diet, VPDPR inhibited fat intake but had no effect on carbohydrate or protein intake. This selective inhibition of fat intake was observed in both overnight-fasted rats presented with food and in ad-lib-fed rats at the beginning of the dark-onset feeding period. It is suggested that this peptide may be a feedback signal to regulate the intake of dietary fat. PMID- 1896501 TI - Pancreatic procolipase propeptide, enterostatin, specifically inhibits fat intake. AB - Pancreatic procolipase is activated by trypsin forming colipase, a cofactor for pancreatic lipase involved in intestinal fat digestion and a pentapeptide named enterostatin. Enterostatin with the sequence Val-Pro-Asp-Pro-Arg (VPDPR) was previously shown to decrease food intake in rats both after peripheral and central injection. In this work enterostatin has been shown to reduce specifically the consumption of a high-fat diet as opposed to a low-fat diet after central injection of Sprague-Dawley rats. After starvation for 18 hours the rats were given a free choice of a low-fat diet (5.2% fat by weight; 14.1% by energy) and a high-fat diet (17.8% fat by weight; 32.8% by energy) in separate containers. After injection of 200 ng of VPDPR into the lateral ventricle, the rats selectively decreased the intake of the high-fat diet by 45% (p less than 0.005), while the intake of the low-fat diet was unaffected compared to saline injection. VPDP after intracerebroventricular injection had totally lost the selective effect on the consumption of a high- fat and a low-fat diet. It is suggested that enterostatin formed during fat digestion from pancreatic procolipase may provide a feed-back signal for the intake of lipid. PMID- 1896502 TI - Sleep structure and EEG power density in morning types and evening types during a simulated day and night shift. AB - The objective of this study was to examine circadian and homeostatic regulation of sleep in humans. In 8 morning types (M-types) and in 8 evening types (E types), sleep was recorded during 3 successive nights and, after shifting sleep to the daytime, during 3 consecutive days. Night sleep was highly similar in the M-types and E-types. Day sleep clearly differed from night sleep in both types: Day sleep was shorter and had a longer first REMS episode. Furthermore, EEG power density recorded during non-REMS in the delta and theta frequency bands was higher during all day-sleep periods. Remarkably, the enhancements did not occur in non-REMS episode 1 but were delayed. This was interpreted as an inhibition of EEG power density at the beginning of sleep, possibly caused by the time course of body temperature and/or by the higher REMS propensity. Also, clear differences between the types became apparent: Only in the E-types, the non-REMS episodes shortened in response to the shift in bedtime, and probably related to this, the time course of EEG power density over consecutive non-REMS episodes became almost flat. It was concluded that the circadian system exerts not only an influence on sleep duration and REMS propensity, but also affects the time course of the non REMS process. PMID- 1896504 TI - Facilitation of shuttle-box avoidance by the platform method: temporal effects. AB - Two experiments were carried out in order to 1) replicate a previous finding according to which the treatment on large platforms (commonly used as control for the stress induced by smaller paradoxical sleep deprivation platforms) can facilitate the acquisition and long-term retention (LTR) of a distributed shuttle box avoidance in rats, and 2) further examine the temporal conditions in which that facilitation can be observed. The results showed that an immediate posttraining treatment lasting 6 hours induced a significant improvement of acquisition both when applied in the light (8 a.m.) and in the dark cycle (8 p.m.), while the LTR (10 and 31 days) seemed to be better preserved when the treatment was applied during the dark cycle. A shorter treatment (3 h) had no effect upon shuttle-box avoidance, regardless of whether it was applied in the dark or in the light cycle and whether it was immediate or delayed for 3 h. In summary, under certain temporal conditions, a posttraining immediate treatment on large platforms can facilitate the acquisition and/or the LTR of shuttle-box avoidance. Stress hormones and/or the enhancement of CNS arousal are suggested to be some of the mechanisms operating in this facilitatory effect. PMID- 1896503 TI - Hepatic and intestinal handling of metabolites during feeding in rats. AB - Changes in hepatic vein, hepatic portal vein and aortal plasma levels of glucose, lactate, nonesterified fatty acids, and D-3-hydroxybutyrate as well as changes in hepatic glycogen and lactate levels were studied during feeding after 12 h of food deprivation in rats. Feeding caused an increase in portal vein lactate concentration and a transient net hepatic lactate uptake that led to hepatic lactate accumulation. As in previous experiments, feeding was associated with hepatic glycogenolysis and net hepatic glucose release, despite a profound increase in portal vein plasma glucose. Net hepatic uptake of nonesterified fatty acids and net hepatic release of D-3-hydroxybutyrate declined during feeding but did not cease, suggesting that hepatic fatty acid oxidation continued throughout feeding. A prandial net intestinal uptake from arterial blood was observed for nonesterified fatty acids and D-3-hydroxybutyrate, while a net intestinal release was found for glucose and lactate. The results are consistent with the idea that under the conditions tested, glucose, lactate and nonesterified fatty acids jointly activate a hepatic metabolic mechanism of satiety. PMID- 1896505 TI - High-fat diets stimulate transient hyperphagia whereas wet diets stimulate prolonged hyperphagia in Fischer rats. AB - The effectiveness of several different kinds of diets in stimulating hyperphagia in Fischer strain rats was compared. Of three different high-fat diets examined, only one stimulated significant hyperphagia and stimulated weight gain; this diet was high in both fat and carbohydrate. However, this hyperphagia and increased weight gain was transient, lasting less than four weeks. A high-sucrose diet stimulated energy intake for only one week. In contrast, adding water to a high starch diet or adding saccharin to a wet diet stimulated energy intake and weight gain for at least ten weeks. Once water or saccharin were removed from these diets, hyperphagia subsided or even turned into hypophagia, until body weights approached control levels. The degree of hyperphagia during the first week did not correlate with subsequent hyperphagia or weight gain. These results suggest that wet diets act by different mechanisms than do dry high-fat and high-sucrose diets. PMID- 1896506 TI - Electromyographic analysis of male rat perineal muscles during copulation and reflexive erections. AB - Anatomical examination of the ventral bulbospongiosus (BS) muscle suggested that its proximal and distal portions may act during penile erection as a two-stage pump governing the intensity of glans erections. The coordination between these portions of the BS, and of the proximal BS with the ischiocavernosus (IC) muscle, was studied using electromyographic (EMG) recordings taken during copulation and reflexive erections. Mounts without intromission were accompanied by either strong IC activity with little or no proximal BS activity, or strong proximal BS activity preceding the onset of IC activity. Activity in the proximal BS during mounts was variable in both duration and amplitude but uniform in frequency. During mounts with intromission, EMG activity of the proximal BS consisted of two characteristic phases, an early phase of low-amplitude activity which was similar to proximal BS activity during nonintromissive mounts, followed by an intromissive phase of high-amplitude, high-frequency activity. During intromission patterns, IC activity reliably preceded proximal BS activity. Ejaculations were accompanied by stronger proximal BS activity than were other copulatory events and were followed by a series of proximal BS and IC bursts lasting for 10-20 seconds. During reflexive erections, EMG activity in the proximal BS was always fusiform and varied with the intensity of erection only in frequency. In contrast to the proximal BS, activity in the distal BS was similar in frequency and amplitude across copulatory and reflexive events. These findings suggest that: a) different motoneuron pools serve the different portions of the BS muscle; b) the distal BS does not differentially affect glans erection but may serve primarily to promote rigidity of the portion of the bulb that it surrounds, while the proximal BS acts as the variable aspect of a hypothetical two-stage pump, and c) activity in the IC must precede activity in the proximal BS to achieve intromission. PMID- 1896507 TI - Feeding behavior in growing rats fed diets containing sorbose. AB - The effect of dietary sorbose on food and water consumption was investigated in growing rats. Rats (26-day old) were fed diets containing 0, 100, 200 or 300 g sorbose/kg diet for 5 weeks in Experiment 1. Daily food and water intakes were measured at day 0, 7, 14, 21, 28 and 35. Absolute food intake (g) until day 21 decreased linearly with increasing sorbose levels and so did relative food intake (g/100 g b.wt.) until day 7. In contrast, relative water intake (ml/100 g b.wt.) and water:food intake ratio (ml/g) remained high by day 7 with increasing sorbose levels. In Experiment 2, the effect of sorbose on the short-term food intake was compared with those of glucose, sucrose and maltitol in growing rats (25-day old) at a level of 100 g/kg diet in order to investigate how quickly reduced food intake would be induced by sorbose consumption. Cumulative food intake was determined every hour for the first ten hours, then at two-hour intervals thereafter during the 24-hour period that followed feeding. As rapid as 6 hours after feeding, cumulative food intake significantly decreased in sorbose-fed animals compared with other dietary groups. It was concluded that sorbose consumption decreased the food intake of growing rats from 6 hours to a few weeks after feeding, but this inhibitory effect disappeared afterwards. PMID- 1896508 TI - Sex differences in the behavioral consequences of inescapable footshocks depend on time since shock. AB - In two experiments, the effects of inescapable shock on subsequent shuttle-box escape performance were studied in male and female rats. Effects of treatment with short-duration shocks (2 s) were studied after 1- and 24-hour intervals (Experiment 1), and effects of long-duration shocks (6 s) were studied after 24- and 72-hour intervals (Experiment 2). Experience with inescapable shock resulted in a serious disruption of escape performance in both males and females. A large increment in escape latencies was found both during fixed ratio 1 and fixed ratio 2 escape training; however, effects of inescapable shock were more pronounced in males than in females. In Experiment 1, sex differences were most obvious after the short 1-hour interval whereas, in Experiment 2, sex differences were only present after 24 hours and not after 72 hours. Shuttle activity during 2-min adaptation prior to shock-escape training was reduced in both males and females treated with IS, and this effect was somewhat stronger in males than in females. The data of these experiments show that male rats are more sensitive to the consequences of exposure to inescapable aversive stimulation than female rats. It is proposed that the time-dependency of the sex differences in behavioral consequences of treatment with inescapable shock may be related to sex differences in transient neurochemical or hormonal changes induced by inescapable shock. PMID- 1896509 TI - Taste reactivity in the hamster. AB - Taste reactivity, which was first described in the rat, consists of ingestive and aversive response components, the latter seen mostly to bitter-tasting stimuli. The present experiment characterized the hamster's taste reactivity to an array of stimuli (sugars: 1 M sucrose, d-fructose and d-glucose; sodium salts: 1 M NaCl, Na2SO4 and NaNO3; acids: 30 mM HCl, tartaric acid and citric acid; bitter tasting stimuli: 100 mM quinine hydrochloride and nicotine sulfate and 10 mM denatonium benzoate). These 12 stimuli were chosen to represent 3 examples each of stimuli that taste sweet, salty, sour, or bitter to humans; they were presented in random order via an intraoral fistula, one stimulus each day per animal (n = 10). Infusions of 0.6 ml were delivered over a 1-min period from a syringe pump. Orofacial and somatic motor responses were recorded on videotape for later analysis and were also coded online into a computer. Ingestive responses included forward and lateral tongue protrusions and aversive responses included gaping, chin rubbing, forelimb flailing, fluid rejection, increased locomotion, and aversive posturing. Each stimulus group produced a characteristic pattern of these behaviors, with sugars eliciting only ingestive behaviors and the bitter stimuli evoking predominantly aversive responses. Both sodium salts and acids produced ingestive responses, as seen previously in the rat, although these stimuli also elicited aversive behaviors in the hamster, including apes. The patterns of responses were characterized using multivariate procedures; the stimuli fell into distinct groups that were separated primarily along an hedonic dimension. PMID- 1896510 TI - Influence of adrenalectomy on the odor detection performance of rats. AB - The influence of adrenalectomy (ADX) on the odor detection performance of male Long-Evans rats was assessed using high-precision olfactometry and a go/no-go operant signal detection task. Nonparametric signal detection measures of sensitivity and responsivity, as well as measures of S+ response latency, the number of aborted trials, and session time, were obtained in daily 250-trial test sessions prior to and after adrenalectomy. Four ADX animals were tested using the odorant pyridine, three using the odorant eugenol, and two using the odorant ethyl acetate. Nine other rats served as sham-operated controls. Neither odor detection nor related nonsensory performance measures were influenced by adrenalectomy or sham-operation procedures. These results imply that adrenalectomy has little or no influence on the odor detection performance of the rat. PMID- 1896511 TI - Lesions of the suprachiasmatic nucleus disrupt circadian locomotor rhythms in the mouse. AB - Entrained and free-running rhythms of wheel-running activity were recorded in male BALB/cByJ mice with electrolytic lesions of the suprachiasmatic nucleus (SCN), site of a circadian pacemaker in mammals. Complete ablation of the nucleus abolished the circadian locomotor rhythm; in some cases, wheel-running was synchronized by a light-dark cycle, but the phase relationship of this activity to the cycle was often aberrant. Unilateral lesions or those missing the SCN did not eliminate rhythmicity. PMID- 1896512 TI - Social facilitation of the spontaneous meal size of humans occurs on both weekdays and weekends. AB - The amount eaten by humans in spontaneously ingested meals is positively correlated with the number of other people present. This could be due to a social facilitation or may occur as an artifact of a covariation produced by changes in intake occurring over weekends. This possibility was investigated by paying 315 adult humans to maintain 7-day diaries of everything they ingested, when and where they ingested it, and the number of other people present. During weekends, larger meals were ingested, in the presence of more people than during weekdays. However, strong, positive, and significant correlations between meal size and the number of other people present were found separately for meals eaten only during week-days and for those eaten only during weekends. The results suggest that the correlation results from a true social facilitation of eating and that this facilitation is an important determinant of the eating behavior of normal humans. PMID- 1896513 TI - Odorant identification in rats: an update. AB - In a previous report, Youngentob et al. (8) described a new and substantially different type of animal psychophysical procedure in which rats were trained to differentially report (i.e., identify) five different odorants. The present study confirms and extends the usefulness of the cross-modal association paradigm as an effective means for developing an extensive nonverbal "vocabulary" with which an animal can communicate multiple changes in sensory stimuli. Given the appropriate nonverbal means of communication, a rat has the channel capacity to differentially report (i.e., identify), at least ten different odorants. The expansion to a ten odorant identification task is discussed with respect to the analytic capabilities of the animal model for the study of olfactory quality perception. PMID- 1896515 TI - Muscle metabolic changes during the first six hours of cohabitation in pairs of male Betta splendens. AB - Muscle metabolic effects of aggression were investigated during the first 6 hours of dyadic contests in male Betta splendens. In the first 10 minutes the free amino acid content of the carcass was reduced. At the end of the fight (after 30 minutes) a significant reduction in glycogen content and an increase in free glucose were noticed while amino acids were still reduced. The reduction in glycogen was more intense, while the increase in free glucose was smaller in losers. These modifications disappeared after 360 minutes, but at this time a significant reduction of protein content (both in winners and losers) and an increase of amino acids in winners were noticed. PMID- 1896514 TI - Neuropeptide K (NPK) suppresses copulatory behavior in male rats. AB - Recent studies show that neuropeptide K (NPK), a member of the tachykinin family of neuropeptides, is found in various hypothalamic sites implicated in the control of gonadotropin secretion, food intake and sexual behavior. Since our previous studies showed that NPK inhibited feeding and gonadotropin secretion in rats, we have now assessed the effects of NPK on sexual behavior in male rats. Copulatory behavior was recorded subsequent to injection of different doses of NPK either into the third ventricle of the brain or intraperitoneally in sexually experienced male rats. We observed that intraventricular (IVT) administration of 0.125 nmol NPK produced only a slight effect on behavior as indicated by a significant increase in intromission latency. However, a four-fold higher dose of 0.5 nmol of NPK completely eliminated copulatory behavior. These rats displayed no overt locomotor deficit but ignored the receptive females, rarely approaching them during the test period. Only two mounts and no intromissions were observed in 6 rats during the test period. In contrast, neither the same dose of 0.5 nmol nor a higher dose of 3.14 nmol injected intraperitoneally produced any discernible effect on sexual performance. These results show that NPK acts centrally to inhibit sexual behavior in male rats and that hypothalamic NPK may be an important part of the neural circuit that regulates reproduction and related behaviors. PMID- 1896516 TI - Sleep patterns in the lizard Ctenosaura pectinata. AB - Specimens of the lizard Ctenosaura pectinata were chronically implanted for polygraphic recordings. Four different vigilance states were observed throughout the nyctohemeral cycle: Active wakefulness (Aw), quiet wakefulness (Qw), quiet sleep (Qs) and active sleep (As). Each state displayed its own behavioral and electrophysiological characteristics. Aw, Qw, Qs and As occupied 5.9%, 25.7%, 67.7% and 0.6% of the 24-h period, respectively. The frequency and the duration of As episodes showed great interanimal variability and the mean duration was very short (12.9 +/- 9 s, mean +/- standard deviation). Stimuli reaction threshold was highest during sleep. It is concluded that the lizard Ctenosaura pectinata exhibits two sleep phases (Qs and As) that may be assimilated to slow wave sleep (SWS) and paradoxical sleep (PS) of birds and mammals. PMID- 1896517 TI - Improvement of hyperglycemia and hyperlipemia in streptozotocin-diabetic rats by a methanolic extract of Prunus davidiana stems and its main component, prunin. AB - Blood glucose and total lipid levels in rats with streptozotocin-induced diabetes were determined after intraperitoneal administration of a methanolic extract of Prunus davidiana Fr. stems and its main component, prunin (= naringenin 7-O-beta D-glucoside). From the data obtained it was concluded that intraperitoneal administration of the methanolic extract and prunin produced a significant hypoglycemic effect. Total blood lipids were also decreased by these substances. Thus, it is suggested that this methanolic extract contains one or more hypoglycemic principles including the main flavanone glycoside, prunin, which can significantly reduce the levels of blood glucose and total lipids in streptozotocin-diabetic rats. PMID- 1896518 TI - Pharmacology of Casimiroa edulis; II. Cardiovascular effects in the anesthesized dog. AB - The cardiovascular effects of an aqueous extract of seeds of Casimiroa edulis were assessed in pentobarbital-anesthetized dogs. The extract produced marked hypotension which lasted more than two hours; it was accompanied by moderate and less persistent bradycardia. The histaminergic nature of these effects was investigated in animals pretreated with the specific antagonists diphenhydramine, cimetidine, or a combination of both agents. These experiments showed that both H1- and H2-receptors were involved in the hypotensive response, while the bradycardia was mediated solely through an H1-mechanism. In open-chest dogs instrumented for recording cardiac output (ascending aortic flow), left ventricular contractility (dp/dt), central venous pressure (superior vena cava), systemic blood pressure, heart rate, total peripheral resistance and stroke volume, the extract decreased blood pressure and peripheral resistance and increased cardiac output and stroke volume, without modifying the other parameters. It was concluded that the cardiovascular pattern of Casimiroa edulis in the dog is that of a peripheral arterial vasodilator and that it increases cardiac output by reducing left ventricular afterload. PMID- 1896519 TI - Inhibitory effects of licochalcone A isolated from Glycyrrhiza inflata root on inflammatory ear edema and tumour promotion in mice. AB - Licochalcone A, 3-a,a-dimethylallyl-4,4'-dihydroxy-6-methoxychalcone, from the root of Glycyrrhiza inflata Beta (Leguminosae) (Xin-jiang liquorice) showed anti inflammatory action towards mouse ear edema induced by arachidonic acid (AA) and 12-O-tetradecanoylphorbol 13-acetate (TPA) by topical application. Anti-tumour promoting action of licochalcone A was also observed in vivo for mouse skin papilloma initiated by dimethylbenz[a]anthracene (DMBA) and promoted by TPA. It inhibited in vitro 32Pi-incorporation to phospholipids in HeLa cells promoted by TPA. A competitive interaction of licochalcone A with the TPA-receptors in the cell membrane has been suggested. PMID- 1896520 TI - Analgesic, antipyretic and anti-inflammatory properties of Euphorbia hirta. AB - Lyophilised aqueous extract of Euphorbia hirta L. (Euphorbiaceae) has been evaluated for analgesic, antipyretic and anti-inflammatory properties in mice and rats, in order to complete its activity profile, after the confirmation of the existence of a central depressant activity particularly expressed by a strong sedative effect, associated with anxiolytic effects. This study leads us to the conclusion that this plant extract exerts central analgesic properties. Such a dose-dependent action was obtained against chemical (writhing test) and thermic (hot plate test) stimuli, respectively, from the doses of 20 and 25 mg/kg and it was inhibited by a naloxone pretreatment, a specific morphinic antagonist compound. An antipyretic activity was obtained at the sedative doses of 100 and 400 mg/kg, on the yeast-induced hyperthermia. Finally, significant and dose dependent anti-inflammatory effects were observed on an acute inflammatory process (carrageenan-induced edema test in rats) from the dose of 100 mg/kg. On the other hand, plant extract remained inactive on chronic processes such as Freund's adjuvant-induced rheumatoid arthritis, after a chronic treatment during fourteen days at the daily dose of 200 or 400 mg/kg; however, if inefficacy was observed on rat backpaws edema and on loss of weight, the aqueous extract reduced the inflammatory hyperalgia. PMID- 1896521 TI - Ribosome-inhibiting proteins from in vitro cultures of Phytolacca dodecandra. AB - Phytolacca dodecandra (L'Herit) grown in cell cultures was investigated for content of ribosome-inhibiting proteins, which was evaluated by measuring inhibition of protein synthesis in a cell-free rat liver extract. Calli initiated from leaf, cotyledon, radicle, and hypocotyl and suspension cells initiated from leaf and cotyledon exhibited protein synthesis-inhibiting activity. Ribosome inhibiting proteins were purified at least 14 times from suspension cells of P. dodecandra. The purified protein fraction contained two proteins as seen by sodium dodecyl sulphate polyacrylamide gel electrophoresis. The relative molecular masses were 30,000 and 31,000 and they showed a pI greater than 9.3. These new RIP's were shown to be different from dodecandrin with respect to molecular mass. PMID- 1896523 TI - 6-Pentadecylsalicylic acid: an antithrombin component isolated from the stem of Rhus semialata var. roxburghii. AB - Bioassay-directed fractionation of the n-hexane extract of the stem of Rhus semialata Murr. var. roxburghii DC (Anacardiaceae) has led to the isolation of 6 pentadecylsalicylic acid. It showed antithrombin activity at 50 micrograms/ml in the amidolytic method. It also prolonged the clotting time in a dose-dependent manner in the clotting assay of thrombin-fibrinogen interaction. PMID- 1896522 TI - Anti-tumor-promotion by principles obtained from Angelica keiskei. AB - Potent anti-tumor promoter activity has been found in the nonpolar extracts of the root of "Ashita-Ba", Angelica keiskei Koidz. (Umbelliferae), which is eaten as a vegetable in Japan. From this active fraction, two angular furanocoumarins, archangelicin (1) and 8(S),9(R)-9-angeloyloxy-8,9-dihydrooroselol (2), three linear furanocoumarins, psoralen (3), bergapten (4) and xanthotoxin (5), and three chalcones, 4-hydroxyderricin (6), xanthoangelol (7) and a novel chalcone named ashitaba-chalcone (8), were isolated. Among these compounds, two angular type furanocoumarins, 1 and 2, and three chalcones, 6-8, suppressed 12-O tetradecanoylphorbol-13-acetate (TPA)-stimulated 32Pi-incorporation into phospholipids of cultured cells, whereas coumarins 3-5 were less effective. In addition, chalcones 6 and 7 were proved to have anti-tumor-promoting activity in mouse skin carcinogenesis induced by 7,12-dimethylbenz[a]anthracene (DMBA) plus TPA. Since chalcones 6 and 7 showed calmodulin-interacting property, both chalcones may reveal anti-tumor-promoting activity via the modulation of calmodulin involved systems. These chalcones may be useful to develop the effective method for cancer prevention. PMID- 1896524 TI - Characterization of mitogenic pectic polysaccharides from kampo (Japanese herbal) medicine "juzen-taiho-to". AB - The acidic polysaccharide fraction (F-5-2) from "Juzen-Taiho-To" (TJ-48), a Kampo (Japanese herbal) medicine prepared by decocting a prescription of 10 kinds of herbs, has potent mitogenic activity. In order to clarify the mitogenic activity, F-5-2 was fractionated by amon-exchange chromatography, and 14 acidic polysaccharide fractions were obtained. Mitogenic activities of these polysaccharides were increasing with their molecular masses and affinities to the anion-exchange column. Methylation analysis and endo-alpha-(1----4) polygalacturonase digestion showed these polysaccharide fractions to be pectic polysaccharides, many of which consisted mainly of polygalacturonan regions in addition to small amounts of "ramified" regions. Gel filtration showed that the molecular masses of the "ramified" regions of the polysaccharides were similar. High molecular mass polygalacturonic acid showed a weak mitogenic activity. The mitogenic (M-1 and M-2) and non-mitogenic (M-3) polysaccharides from the most active polysaccharide fraction (F-5-2IIh) were further purified by gel filtration. M-2 and M-3 were also shown to be pectic polysaccharides, and the neutral glycosidic linkages in M-2 and M-3 were different from each other. Endopolygalacturonase digestion markedly decreased the mitogenic activity of M-2, however, the "ramified" region of M-2 still showed a weak activity. PMID- 1896525 TI - Saponins of the ivy plant, Hedera helix, and their leishmanicidic activity. AB - Antileishmanial activity is reported for the first time for saponins of ivy, Hedera helix L., in vitro on promastigote and amastigote forms of Leishmania infantum and Leishmania tropica. The compounds tested were an extract containing 60% of saponic complex (CS 60), the bidesmosides hederasaponin B, C, and D (saponin K10), their corresponding monodesmosides alpha-, beta-, and delta hederin, and hederagenin. CS 60 and bidesmosides have shown no effect. Monodesmosides were found to be as effective on promastigote forms as the reference compound (pentamidine). Against amastigote forms only hederagenin exhibited a significant activity which was equivalent to that of the reference compound (N-methylglucamine antimonate). PMID- 1896526 TI - Effect of abietane- type pigments from Salvia miltiorrhiza on post-hypoxic recovery of cardiac contractile force in rats. PMID- 1896527 TI - Antimalarial activity of some natural peroxides. PMID- 1896528 TI - Craniofacial suture stenosis: morphologic effects. AB - Craniofacial anomalies, such as Apert's and Crouzon's syndromes, are presumed to be related to premature growth arrest of cranial base growth sites. However, premature growth arrest at cranial vault sutures in animals appears to play a causative role in the development of cranial deformities characteristic of single suture, or simple, craniosynostosis in humans. To study the possible causative role of cranial vault and other (interface) suture stenoses on the development of craniofacial deformity, a vault suture and an interface suture between the cranial vault and facial skeleton were simultaneously immobilized. Thirty-one New Zealand White rabbits at 9 days of age underwent implantation of dental amalgam growth markers adjacent to cranial vault and facial sutures. In the experimental group (n = 15), methylcyanoacrylate adhesive was applied over the coronal (vault) and frontonasal (interface suture between vault and facial skeleton) sutures to immobilize them. The remaining 16 animals served as sham-treated controls. All animals underwent serial radiographic cephalometry to document growth effects in the cranial vault, cranial base, and facial skeleton. Application of adhesive resulted in statistically significant (p less than 0.05) reduction in growth at the coronal and frontonasal sutures. This was accompanied by an overall significant reduction in neurocranial vault length during the first 30 days of development.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1896529 TI - Aesthetic improvements in free-flap mandible reconstruction. AB - Mandible reconstruction with free flaps has become a well-established technique. Efforts are now focused on obtaining superior functional and aesthetic results. Improvements in the quality of the latter are possible with a systematic approach to shaping the bone graft. Important elements in this approach have been defined based on experience in 50 consecutive cases. Preoperative studies include the lateral cephalogram and a transverse plane CT scan from which mandible templates are constructed. These templates are models of the mandible in two planes and are used to shape the bone with a high degree of precision. They allow the bone to be completely shaped while still attached by the pedicle at the donor site. The surgical specimen serves as an additional key visual reference and as a source of measurements to determine overall bone-graft length. Miniplates alone provide sufficient fixation to stabilize the bone as it is shaped segment by segment. Intermaxillary fixation is used only to prevent errors in total bone-graft length. Hemimandible and anterior defects represent two completely different bone shaping problems. Although the bone-shaping methods described have been developed primarily with the fibula, they have been successfully applied to the scapula and radius donor sites as well. PMID- 1896530 TI - Use of the AO plate for immediate mandibular reconstruction in cancer patients. AB - Free vascularized bone grafts have revolutionized mandibular reconstruction, yet their use in all mandibulectomy patients is not always necessary. A recently developed alternative to bony reconstruction has been the use of the AO reconstruction plate. We compared the use of the AO reconstruction plate with immediate free bone graft mandibular reconstruction in 31 patients. Reconstruction plates were used in 20 and immediate free bone grafts were used in 11 patients. The overall success rate for use of the plate was 15 of 20 (75 percent). There were 6 anterior reconstructions, of which only 2 (33 percent) were successful. This is opposed to 13 of 14 (93 percent) lateral reconstructions that were successful in lateral plate placements. There were 11 immediate composite free flaps: 4 iliac crest, 4 scapula, 2 fibula, and 1 composite radial forearm flaps. Six repairs were for anterior defects, and there were 5 full thickness defects, 3 of which were in the anterior position. All 11 flaps were successful. In conclusion, we believe the reconstruction plates are a useful adjunct for mandibular replacement in the head and neck cancer patient but should be reserved for lateral defects. For anterior reconstructions, even in patients with locally advanced disease, free-tissue transfer of composite osteocutaneous flaps is the reconstructive method of choice. PMID- 1896531 TI - Plastic surgery and psychotherapy in the treatment of 100 psychologically disturbed patients. AB - This paper reviews the senior author's long-term experience with the surgical psychiatric treatment of 100 aesthetic surgery patients with significant psychological disturbances. Patients with psychological disturbances of a magnitude generally considered an "absolute contraindication" for surgery were operated on and later assessed to determine the psychological impact of surgery. Patient follow-up averaged 6.2 years (maximum follow-up 25.7 years). Of the 87 patients who underwent operation (7 patients were refused surgery and 6 voluntarily deferred surgery), 82.8 percent had a positive psychological outcome, 13.8 percent experienced "minimal" improvement from surgery, and 3.4 percent were negatively affected by surgery. There were no lawsuits, suicides, or psychotic decompensations. Patients with severe psychological disturbances frequently benefited from combined surgical-psychiatric treatment designed to address the patient's profound sense of deformity. This study suggests that plastic surgeons are "passing up" a significant number of patients who may be helped by combined surgical-psychological intervention. PMID- 1896532 TI - Microorbitalism: a technique for orbital rim expansion. AB - A simple technique for orbital aperture expansion to facilitate placement of ocular prostheses is described. Both superolateral and inferolateral orbital margins are released by means of a single burr hole craniectomy of the frontosphenoid bone behind the orbital process of the frontal bone. Vertical and horizontal marginal lengthenings are performed by a rotatory displacement of one bone segment alongside the other. The expanded osseous aperture is secured with wire and plate-and-screw fixation following a supraorbital rim craniectomy to allow an adequate fit. The result provides for easier access of ocular prostheses and tissue expanders. The method has been applied to a series of patients with microorbitalism due to unilateral or bilateral congenital anophthalmia over the past 3 years without complication and with excellent results. Three-dimensional re-formatted CT reconstructions of the craniofacial skeleton are shown preoperatively and postoperatively. PMID- 1896533 TI - Staged sequential flap reconstruction for large lower lip defects. AB - A method for the reconstruction of total or nearly total defects of the lower lip is described that utilizes a staged sequence of flaps that are familiar to most plastic surgeons. The recommended sequence is an extended Karapandzic flap to reestablish the oral sphincter, then two sequential Abbe flaps from the upper lip to restore balance and augment the central lower lip, and finally a commissureplasty using a sliding myomucosal flap in conjunction with final revision of the scars. Intervals of 3 weeks separate the surgical procedures. Using this strategy, essentially normal lip function and a relatively normal appearance have been obtained in four patients with large lip defects. PMID- 1896534 TI - Selection criteria for successful immediate breast reconstruction. AB - To evaluate the factors leading to success in immediate breast reconstruction after mastectomy, 176 consecutive immediate reconstructions done with implants or expanders over a 5-year period were analyzed. None of these 176 had "complete muscle coverage." There were only five failures: four with implant loss (one involving radiation) and one removed electively. The failures were 1 in 40 regular implants, 4 in 77 temporary expanders, and 0 in 59 long-term expanders. There is no other report in the literature comparing these different types of implants. Various hypotheses for failure are reviewed. It is concluded that failure in immediate reconstruction is not related to use of drains, bilaterality, or lack of "complete muscle coverage." It is concluded that failure is related to implant type, prior radiation, and most of all to suboptimal patient selection. Specific selection criteria and operative techniques are discussed. PMID- 1896535 TI - Breast reconstruction utilizing subcutaneous tissue expansion followed by polyurethane-covered silicone implants: a 6-year experience. AB - Reconstruction of the breast after modified radical mastectomy can be safely and adequately performed in the subcutaneous plane. Placement of a subcutaneous tissue expander (as either an immediate or a delayed procedure), rapid expansion over a 3- to 4-month period, capsulotomy, and placement of a polyurethane-coated implant have led to satisfactory results over a 6-year period. Breast reconstruction methods are well documented; however, the utilization of expanded subcutaneous chest wall skin has not been reported heretofore. PMID- 1896536 TI - Circulatory and metabolic changes in expanded pig skin flaps. AB - To evaluate circulatory and metabolic changes in pig skin during tissue expansion, the buttock skin of 12 pigs was expanded for 5 weeks. In a second operation, island buttock flaps were elevated bilaterally. Flap temperature, laser Doppler flow (LDF), and fluorescein penetration borders were recorded. Norepinephrine infusions were given twice. After cannulation of the external iliac veins, the total venous outflow from the flaps and metabolic parameters such as glucose and oxygen consumption and lactate production were measured bilaterally. No significant difference in fluorescein staining was found, but laser Doppler flow in the expanded tissue was higher than in nonexpanded skin, whereas the total flap blood flow was not significantly different. A flow reduction was seen in expanded flaps during norepinephrine infusion, whereas nonexpanded flaps showed a slightly increased blood flow. This adrenergic supersensitivity indicates that it is possible that not only surgical nerve section but also tissue expansion can result in sympathetic denervation. No differences in the metabolic parameters were observed. PMID- 1896537 TI - Hydrogen clearance: assessment of technique for measurement of skin-flap blood flow in pigs. AB - The hydrogen clearance technique has been used for many years by investigators to determine brain blood flow and has been partially validated in this setting using other methods of blood flow measurement. The method has been modified to allow blood flow measurements in skin, but the accuracy of H2 clearance for measuring skin blood flow has not been determined. Multiple blood flow measurements were performed using H2 clearance and radioactive microspheres on skin flaps and control skin in pigs. On 12 pigs, a total of 117 flap and 42 control skin measurements were available for analysis. There was no significant difference between the two techniques in measuring mean control skin blood flow. In skin flaps, H2 clearance was significantly correlated to microsphere-measured blood flow, but it consistently gave an overestimate. Sources of error may include injury to the tissues by insertion of electrodes, consumption of H2 by the electrodes, or diffusion of H2 from the relatively ischemic flap to its well vascularized bed. Further studies are necessary to determine the cause of this error and to measure the technique's accuracy in skeletal muscle and other flaps. PMID- 1896538 TI - Fuel metabolism in a pig myocutaneous island flap model. AB - Unilateral denervated myocutaneous island flaps based on the superior epigastric vessels were raised in 24 pigs and the metabolic changes during the first 6 postoperative hours were monitored. Secondary to flap elevation, decreased arteriovenous (A-V) differences in oxygen, glucose, and alanine levels were observed, indicating the opening of A-V shunts and increased arterialization of the venous blood. Venous outflow increased during the first 3 hours, but the A-V differences in all metabolites were constant over the entire 6-hour observation period. Exchange of intermediary metabolites therefore increased within the first 3 hours, after which a steady state was established. The main flap fuels seemed to be fatty acids, muscle proteins, and glycogen, whereas blood-borne carbohydrates and ketone bodies played only a minor role as energy sources. Anaerobic metabolism was increased secondary to flap elevation from 2 to 6 percent as compared with preelevation values. No changes were found in concentrations of plasma catecholamines, which were constantly high. An average weight gain of 3 to 4 percent per hour was equally distributed to skin, subcutis, panniculus carnosus, and muscle. Thus the flap seemed to adapt to the new perfusion pattern within a few hours by a slightly increased anaerobic metabolism, but still with an oxidative metabolism of more than 90 percent. PMID- 1896539 TI - Management of the recalcitrant total-hip arthroplasty wound. AB - The infection rate for total-hip arthroplasty is around 1 percent. This small group is usually managed by complete removal of the prosthesis and the cement and closure over suction catheters to "collapse" the wound and eventually achieve a girdlestone arthroplasty. Occasionally, there are patients who have a persistent draining wound after this treatment and repeated efforts at wound closure. We present 27 patients who had recalcitrant, noncollapsible wounds of the hip that were present for many months to years. Twenty-eight cases of infected total-hip arthroplasties that did not respond to removal of the prosthesis and cement and closure were seen by the authors between January of 1977 and December of 1988. One patient had bilateral involvement. Average age was 64 years (range 33 to 79 years). There was an average of 4.2 previous surgical attempts at closure (range 1 to 21). Staphylococcus aureus was the most common organism, but the infections were virtually all multiple. Thirty-three muscles were utilized in 27 patients. The rectus femoris was used in 23 cases, the vastus lateralis in 8, tensor fasciae latae in 1, and combined latissimus dorsi-serratus anterior free-tissue transfers were carried out in 2. Multiple combinations of transpositions and free flaps were utilized. Follow-up ranged from 1 to 10 years, with an average of 6.4 years. Eighteen patients were ambulatory with minor degrees of pain, five ambulated with a cane, seven ambulated with a walker, six ambulated with crutches, and four ambulated unassisted, all of whom had reimplantation of their hip arthroplasty at least 12 months following the muscle flap procedure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1896540 TI - Functional assessment of neurologic impairment: track analysis in diabetic and compression neuropathies. AB - A laboratory approach to measuring neurologic impairment has been developed that is applicable to systemic disease as well as localized nerve injury. This approach compares individual parameters of the experimental rat hind footprint (walking track) with weight- and sex-matched control track parameters; classic mathematical indexing is not utilized. The normal track data obtained for the Sprague-Dawley rat showed a significant increase in print length (PL), toe spread (TS), and intermediate toe spread (ITS) with increasing rat weight. A significant difference between male and female rats above 400 gm also was noted. For a localized injury (sciatic nerve cut), this approach demonstrated that the contralateral hind footprint was a "compensated" rather than a normal track. This approach to track analysis also was capable of demonstrating progressive neurologic impairment for a sciatic nerve compression model and a systemic disease such as diabetes, as well as demonstrating reversal of these abnormal patterns when the "disease state" was treated. PMID- 1896541 TI - The healing partnership. PMID- 1896542 TI - Public relations. PMID- 1896543 TI - An unknown syndrome of nose deformity, oxycephaly, aplasia of the nasolacrimal ducts, and symmetrical cyst formation on the upper lip in siblings: craniorhiny. AB - An unknown syndrome of oxycephaly, nose deformity, hair growth on the skin at the base of the nose, symmetrical cyst formation on the upper lip, and aplasia of the nasolacrimal ducts in a mother and her three children is presented. This syndrome showed autosomal dominant inheritance. All three children were operated on. Oxycephaly and lip deformity in two of the children and hypertelorism that existed in addition to the other anomalies in the third were all corrected. All corrective surgery was performed during a single session for each child. PMID- 1896544 TI - Bilateral gluteal thigh flaps for closure of large defects in the lumbosacral region and perineal region. AB - Large defects in the lumbosacral and perineal regions were reconstructed with bilateral gluteal thigh flaps. These two patients demonstrate the versatility of the flap, which also was used as a sensory flap in one patient. PMID- 1896545 TI - Double-layered free temporal fascia flap as a two-layered tendon-gliding surface. AB - We report the use of a two-layered free fascial flap consisting of temporoparietal and deep temporal fascia based on a single vascular pedicle, the superficial temporal artery and vein. The flap was used to reconstruct an extensive degloving injury of the dorsum of the hand, in which multiple intact extensor tendons lay fully exposed on all sides, with exposed bone beneath them. By sandwiching the tendons between the layers of vascularized fascia, gliding surfaces were provided, both superficial and deep to the exposed tendons. The single-stage reconstruction was completed with a split-thickness skin graft. The patient returned to heavy manual work within 12 weeks of injury. He obtained an excellent range of movement without the need for tenolysis. PMID- 1896546 TI - Transplantation of an osteoarthrotendinous allograft with autogenous soft-tissue coverage for thumb reconstruction. AB - A fresh-frozen thumb osteoarthrotendinous allograft and autogenous coverage were used to reconstruct a thumb. Immunosuppressants were not used. The components of the composite allograft are present and functioning 1 year post-operatively. Host cells have replaced and are replacing bone and tendinous structures. The "survival" of this osteoarthrotendinous allograft may have important implications in the treatment of patients with previous digital amputations, congenital absence of digits, and amputated digits that have failed replantation or are not replantable because of severely damaged vessels. PMID- 1896547 TI - Reconstruction of the medial half of the lower eyelid using a "switch" split-lid procedure. AB - Reconstruction of the medial half of the lower eyelid has one major disadvantage: It produces a scar at right angles to the eyelid rim. In contrast, use of a "switch" split-lid procedure avoids this inconvenience. The lateral half of the lower eyelid is split in two lamellae. The inner layer is transferred medially, and the resulting defect is closed with a buccal graft. The outer layer is drawn laterally to cover the raw surface of the mucosal pedicle and graft. The surplus of skin over the lateral canthal area is removed. This procedure, which so far has been used in three patients, promises to be a useful alternative for reconstruction of the medial half, but not more, of the lower eyelid. PMID- 1896548 TI - Selective photothermolysis and removal of cutaneous vasculopathies and tattoos by pulsed laser. AB - The evolution of the laser as a medical device has been a process of continued improvement. Research into increasing our understanding of the optical characteristics of skin has made it possible to concentrate not on the effects of any particular laser system, but on basic biologic and physical principles of laser-tissue interaction. The lasers available in the 1960s and 1970s offered few possibilities for modification. However, modern technology allows us to manipulate the physical characteristics of lasers and design them for specific therapeutic purposes. Selective photothermolysis relies on chromophore-specific absorption of a brief pulse of light to generate and confine heat to certain targets within the skin without nonspecific thermal damage to adjacent structures. Thermally mediated target alterations can be confined from the level of large multicellular tissue structures (e.g., blood vessels) to individual microscopic pigmented structures (e.g., tattoo pigment granules). The purpose of this report is to describe the current progress being made and to summarize the present theories for achieving increasing selective removal, without scarring or other skin textural changes, of cutaneous vasculopathies and tattoo pigment by pulsed laser. PMID- 1896549 TI - Breast reconstruction with the inflatable expander. PMID- 1896550 TI - Silvadene toxicity. PMID- 1896551 TI - Autologous fat transplantation. PMID- 1896552 TI - A microruler for microsurgery. PMID- 1896553 TI - Relatively inexpensive computer imaging systems. PMID- 1896554 TI - Digital Allen test as an adjunct in diagnosis of possible digital nerve lacerations. PMID- 1896555 TI - Nasotracheal intubation versus tracheostomy in the presence of facial fractures. PMID- 1896556 TI - [Habermas, Freud and rationality. Psychoanalysis as a focus of the theory of communicative interaction]. AB - In his Theory of Communicative Action (1981) Jurgen Habermas attempted to base the critique of society on a universalized pragmatics. Heim attempts to derive a new metatheory of psychoanalysis from the theory of communicative action. In doing so he concentrates on the actual models of interpretation in psychoanalysis (Lacan, Marcuse, Lorenzer). PMID- 1896557 TI - [Neurosis--sequela of erroneous organization of speech?]. PMID- 1896558 TI - [Psychoanalytic knowledge in the individual case: possibilities and limits]. PMID- 1896559 TI - [The physician and the image]. PMID- 1896560 TI - [Pediatric radiology: between the devil and the deep sea]. PMID- 1896561 TI - [Comparison of colpocystourethrorectography and transrectal ultrasonography in the assessment of female urinary incontinence]. AB - In order to investigate the diagnostic reliability of transrectal US in the study of female urinary incontinence, the authors compared the static images obtained by means of colpocystourethrorectography with the ones obtained with transrectal US. The study population included 30 patients suffering from urinary incontinence. US images were obtained both at rest and during Valsalva's maneuver, some minutes before cystourethrography and employing part of its preparation (vesical filling with 250 cc of iodine contrast medium and positioning of a metallic bead chain in the urethra). On static images obtained with cystourethrography and transrectal US both at rest and during Valsalva, 4 parameters were evaluated: anterior and posterior vesical angles, urethral axis angle, and distance between symphysis pubis and urethral-vesical junction. As for posterior vesical angle, urethral axis angle, and symphysis-junction distance, the statistical comparison of the results did non demonstrate any significant differences. Anterior vesical angle was not included because it is too difficult to measure by transrectal US. In our experience, transrectal US was capable of yielding accurate information similar to that obtained with colpocystourethrorectography. PMID- 1896562 TI - [Thoracic X-ray in intensive care]. PMID- 1896563 TI - [Integrated Doppler ultrasonography of the abdomen in diagnostic imaging]. PMID- 1896564 TI - [Leukodystrophies: clinical aspects and findings with computerized tomography and magnetic resonance imaging]. AB - Leukodystrophies are inherited white matter diseases due to abnormalities occurring in myelin synthesis and/or maintenance. The most common types of these rare childhood conditions are represented by adrenoleukodystrophy, metachromatic leukodystrophy, Canavan's, Alexander's, Krabbe's, and Pelizaeus-Merzbacher's diseases. Most of them are lethal during childhood, with the exception of the adrenoleukodystrophy-adrenomyeloneuropathy complex, which sometimes, during its early phases, may be cured with a dietary therapy. The aims of this paper are: 1) the description of inheritance factors, pathogenesis, pathological and clinical findings of each of the most frequent childhood leukodystrophies; 2) the description of the most common patterns of these conditions on CT and MR imaging; 3) the evaluation of the diagnostic capabilities of these two imaging techniques and the comparison of their results. Finally, some of the therapies suggested for the mild forms of these conditions are discussed. The evaluation of leukodystrophic patients with CT and MR imaging shows both imaging modalities to have high sensitivity, thanks to the detection of abnormally myelinated areas, which appear hypodense on CT and hyperintense on T2-weighted MR images. Frequently, both imaging modalities exhibit high specificity as well: they allow a differential diagnosis between the different types through the demonstration of their location in the early stages and of their mode of spread. The most typical example is represented by adrenoleukodystrophy, which is the most common type of leukodystrophy: the frequent occipito-parietal onset and the anterior and caudal progression allow a correct diagnosis to be made on CT and MR images in most cases. The comparison between CT and MR findings demonstrates a slight superiority of the latter: multiplanarity and high contrast resolution make MR imaging more sensitive than CT in the detection of both caudal spread and involvement of optic and acoustic nervous pathways. Furthermore, MR imaging allows a safe follow-up in children with leukodystrophy. PMID- 1896565 TI - Geometric mispositioning in positron emission tomography. AB - The phenomenon of geometric mispositioning (defined as having a geometric proper plus a parallax component) was studied and characterized on Neuro- and whole body PET systems employing 2-D modular detectors (CTI/Siemens ECAT-831/08 and 931/08) as well as an older system (CTI ECAT-911). Measurements taken with precisely spaced line sources showed image distortions of objects away from the center of the field of view (FOV), with global mispositionings of -1.4, 1.5 and 14 mm (931 and 911), and -0.5, 10 mm (831) at 10, 20 and 30 cm (931 and 911) and 10, 20 cm (831) from the center of the FOV. Structures as close as 5 cm (931/911) or 4 cm (831) to the center of the FOV are mispositioned by more than 1 mm. This is clearly inacceptable in cases where accurate correlation of PET and NMR images is needed to acquire anatomical information in neurological studies, or when gated cardiac studies are performed in order to precisely determine myocardial wall thickness. A fast, on-line geometric correction was performed by creating new, uniformly spaced sinograms to be mapped to the original sinograms. Geometric mispositioning was mathematically derived, while parallax mispositioning was estimated by a linear fit of the data partially corrected for sampling non uniformity. Our correction technique can be easily tailored to any PET system available on the market. PMID- 1896566 TI - [Recurrence after radiotherapy and/or surgery of carcinoma of the oropharynx and the pharynx. Possibilities of salvage surgery]. AB - Forty-seven laryngeal and 21 oropharyngeal recurrences were treated with salvage surgery alone or combined with radiotherapy at the ENT Clinic and Radiotherapy Division of the University of Turin, Italy. Primary tumors had been treated with surgery alone in 10 cases (larynx) and in 21 cases (oropharynx), with combined surgery and radiotherapy in 2 and 8 patients, and with radiotherapy alone in 9 and 18 cases. We observed 26/47 (larynx) and 12/21 (oropharynx) recurrences at the site of primary tumor, 20/47 and 9/21 in loco-regional nodes, and 9/47 and 3/21 in locations adjacent to the primary tumor. Salvage treatment employed surgery alone in 12 (oropharynx) and 16 (larynx) cases; radiotherapy was combined in 9 and 31 cases. Five-year actuarial NED survival was 45.5% for laryngeal and 24% for oropharyngeal cancer patients. After salvage surgery, 50% of laryngeal lesions and only 25% of oropharyngeal recurrences were completely cured. In our series, in 2 cases only the complications caused the patient's death, while in the extant cases a prolonged postoperative hospitalization was necessary. Our study was aimed at investigating the curative potentials of secondary therapy for recurrent carcinomas. A review of the literature on the subject is reported. The small amount of published data prevents "universal" treatment protocol from being assessed. The authors suggest the opportunity of employing a multimodal treatment policy for recurrences of head and neck cancers. PMID- 1896567 TI - [Endocavitary curietherapy of tumors of the rhinopharynx after external radiotherapy]. AB - We report our experience in the treatment of nasopharyngeal carcinoma with intracavitary curietherapy to cure small recurring carcinomas or residual local disease 2-6 weeks after completing external radiotherapy. Since 1984, 10 patients have received intracavitary radiotherapy with customized molds charged with Ir 192. Six of them received a boost dose because of residual disease and for local recurrence. The technique we employed to shape the molds is described, together with the mode of use and the doses to target volume. Due to both the small number of treated cases and the short follow-up, no significant conclusions could be drawn relative to survival time. However, it must be stressed that this therapeutic approach gives a high local control rate with no severe side-effects or sequelae. PMID- 1896568 TI - [The in vivo use of bromodeoxyuridine for the study of cell kinetics in squamous tumors of the neck and head. Implications for the radiotherapist]. AB - Cell kinetics in 22 human epidermoid head and neck tumors were studied in vivo using bromodeoxyuridine (BUrD). Patients were infused with 250 mg/m2 of intravenous BUrD in a variety of sites (oral cavity, pharynx, larynx and lip) four/five hours prior to biopsy. BUrD incorporating cells were detected by flow cytometry using anti-BUrD monoclonal antibodies. Ploidy (DNA index) labelling index (LI%), duration of S-phase (Ts) and potential doubling time (Tpot) could be measured within 12-24 hours from sampling in 77%, 72%, 63 and 63% of cases, respectively. Six failures (few viable cells in biopsy specimen and difficulties in BUrD cell analysis and DNA staining) were recorded. Labelling index values in this study ranged from 2.2% to 28% with a median value of 11%. The median total LI% of diploid tumor (n = 7) was 5% compared to 13% in aneuploid tumors (n = 7). Ts measurement ranged from 6.5 hours to 12 hours, median value being 10.5 hours (euploid tumors: 6.5, aneuploid 12). The calculated potential doubling time ranged from 2.6 to 15 days and the median Tpot was shorter at 5.0 days (euploid tumors: 7 days, aneuploid 4 days). 70% of the tumors had potential doubling time of 5 days or less. Potential doubling time did not correlate with ploidy and tumor or neck nodes status while shorter Tpots were observed in moderate or poorly differentiated tumors. Our data strongly suggest BUrD technique as a useful tool for studying the proliferative behavior of human tumors: the pre treatment knowledge of individualized potential doubling times for the tumors scheduled for irradiation could help the radiotherapist to choose the more effective fractionation regimen (i.e.: accelerated fractionation for tumors with Tpot less than or equal to 6 days and standard fractionation for tumors with higher values. PMID- 1896569 TI - [Giant trigeminal neurinoma. Problems of differential diagnosis in a case with unusual clinical presentation]. PMID- 1896570 TI - [Osteoid osteoma of the acetabular cavity. CT and MR study. Presentation of a case]. PMID- 1896571 TI - [Dorsal defect of the patella]. PMID- 1896572 TI - [Diagnosis of traumatic diaphragmatic hernia in acute phase. Description of 3 cases]. PMID- 1896573 TI - [A clinico-radiologic case of late occlusion of aortorenal bypass treated with locoregional thrombolysis]. PMID- 1896574 TI - [Traumatic rupture of the pericardium: description of a case]. PMID- 1896576 TI - [Diffuse cutaneous eruptions after encephalic radiotherapy]. PMID- 1896575 TI - [Renin-secreting tumor. Description of 2 cases]. PMID- 1896577 TI - [Again on radiology research at the Genoa Congress]. PMID- 1896578 TI - [Magnetic resonance in the tunnel carpal syndrome. Possibilities and perspectives of an etiopathogenetic study]. AB - Thirty-four selected patients were evaluated in order to define MRI capabilities in the preoperative evaluation and characterization of the pathogenetic patterns of carpal tunnel syndrome (CTS). MRI examinations were performed by means of a superconductive unit (1.0 T, Magnetom): SE T1 (500/17) and T2 (2000/90) axial images of the carpal region were obtained with a round surface coil. In 8 patients 3D GE (FLASH) pulse sequences were used to obtain 32 images of the hand; 3D reconstruction was also applied. Six patients with rheumatoid arthritis and amyloidosis were also studied after i.v. injection of Gd-DTPA (0.2 mM/kg). MRI findings were compared with both clinico-electrophysiologic and surgical results. High agreement was observed only between MRI and surgical findings. MRI allowed the direct demonstration of carpal tunnel abnormalities in 8 cases, while abnormal findings in the median nerve were observed in 18 patients. The possibility of depicting medial nerve lesions on T2-weighted images when no direct demonstration of the cause of compression is possible, could represent a guideline for the etiopathogenetic investigation of CTS. However, further experience in selected patients is necessary to define all the aspects relative to this very common syndrome. PMID- 1896579 TI - [Conventional radiology in the choice of surgical treatment of gonarthrosis]. AB - Gonarthrosis is a pathologic condition the incident of which is high in people over 50. Its etiologic factors are varus-valgus deformities, traumatic lesions, meniscal tears, osteochondritis, and metabolic diseases. The authors report their experience with the setting of a radiographic protocol for the study of 100 patients over 50. The protocol allowed both detection and quantification of: varus and valgus deformities studied in weight-bearing (teleradiography in weight bearing) and extensor mechanism malalignment (tangential views); chondral wear of femoral and tibial joints (varus and valgus radiographs); varus and valgus knees instability (varus and valgus radiographs). The results are extremely satisfactory: this protocol allowed correct gonarthrosis grading and the evaluation of such associated lesions as lateral instability. The surgeon is thus provided with the essential elements for the choice of the correct treatment. PMID- 1896580 TI - [Evaluation of fracture healing with the computerized analysis of radiographic images]. AB - The radiographic evaluation of fracture healing in the long bones utilizes subjective and hardly analytic standards. Therefore, to solve this problem, the authors suggest using a computerized image processing system which increases radiographic informative content and allows an objective evaluation of fracture healing. We analyzed the radiographs of 15 patients suffering from femoral fracture and treated by means of Kuntscher nailing. We processed the radiographs taken both before and 1, 2, 4, and 6 months after surgical treatment. It was thus possible to select the regions of interest, to graph brightness levels and to measure both distances and areas. Computerized image processing provides an objective and quantitative analysis of radiographs and allows an increase in informative content. It also allows the comparison of pre- and postoperative radiographs with those taken at different times. Our results may confirm the utility of computerized image analysis of radiographs to evaluate bone remodelling during fracture healing. PMID- 1896581 TI - [Rates of recall for thorough examination and surgical biopsy following mammographic screening. Experience with the screening program in Florence]. AB - The authors evaluate the recall and biopsy rates during three years of mammographic screening. Recalls (373/25970 = 1.4%) were more frequent at the first (2.3%) than at subsequent screening rounds (1.2%) whereas the predictive value for cancer increased at further screening (11.7 vs 21.7%). Recalls are less frequent in older women, particularly at further screening (40-49 vs 50-59 vs 60 70: 1.7 vs 1.1 vs 0.9%) whereas predictive value is higher (14.8 vs 16.5 vs 36.5%). The presence of mammographic abnormalities accounts for the majority of recalls (1.3%) whereas subjective symptoms other than pain are a less frequent cause of recall (0.2%) although as predictive (22.7 vs 20.4%). Calls for biopsy were limited to cases with suspicion for cancer and this allowed a low biopsy rate (75 = 0.3%) and a high predictive value (92%). The observed results have greatly improved with respect to the past years, due to a higher specificity of recall criteria and to the systematic use of all modern tests (high frequency US, fine-needle aspiration cytology, either manual or US-guided or stereotaxic) at the time of diagnostic assessment. All screening programs, particularly the new ones, should monitor recall and biopsy rates and predictive values as they are indicators of efficiency. PMID- 1896582 TI - [Ultrasonography and computerized tomography in giant Baker's cyst]. AB - The US study of the posterior compartment of the knee usually allows the clinical suspicion of popliteal cyst to be confirmed. Nevertheless, in case of giant Baker's cysts--which are, at any rate, less frequent--US diagnosis is more difficult. CT can help determine the benign nature of the lesion, and allow an accurate spatial evaluation. Moreover CT, when accurately performed, demonstrates the caudal or cranial cystic spread, together with its clear separation from adjacent muscular tissues. Direct coronal scans are more useful to obtain better spatial definition than reformatted images. PMID- 1896583 TI - [Duplex study of primary venous insufficiency of the legs. First results and methodologic comparison]. AB - Primary venous insufficiency is a pathologic condition characterized by reflux in the deep venous system not secondary to phlebothrombosis. The authors compare the diagnostic capabilities of duplex and Doppler US in the evaluation of this condition. At present, Doppler US has a more widespread use than the duplex method. Both lower limbs were examined in 46 patients known to be affected with mono/bilateral primary venous insufficiency thanks to previous retrograde phlebography. Ten patients with different phlebopathies and 10 healthy volunteers were also studied as a control group, duplex US had 92% sensitivity and 90% specificity, while Doppler had 86% and 75%, respectively. Duplex US appeared to be more accurate than Doppler in locating and quantifying the reflux. Finally, the authors draw attention to the segmentary reflux phenomenon they observed in asymptomatic patients and suggest the possibility of recognizing the preclinic stage of this condition by duplex US, which is a non-invasive and relatively inexpensive method. The latter could become, thanks to its intrinsic characteristics, the method of choice for monitoring. PMID- 1896584 TI - [Ultrasound-guided percutaneous injection of ethanol in Plummer's adenoma. Our experience with 8 patients]. AB - The authors report their experience in the study of 8 patients showing symptoms of thyroid hyperfunction (Plummer's adenoma) and treated with US-guided percutaneous ethanol injection. The treatment consisted in injecting sterile ethanol in varying amounts (2 to 5 ml) according to nodule size, using a fine needle under US guidance. The patients underwent 3 to 6 injections, according to biochemical (T3-T4-TSH) and scintigraphic findings. Follow-up at 12 months showed regression of clinical symptoms, a trend of hormone levels toward normalization and recovery of previously suppressed parenchymal function. No significant complications were observed, except for a transient thyrotoxic crisis in the patient bearing the largest nodule. The treatment of Plummer's adenoma by means of percutaneous ethanol injection under US guidance appears to provide specific clinical and technical advantages over other conventional treatments. PMID- 1896585 TI - [Computerized tomography in pulmonary cystic fibrosis]. AB - This study was aimed at evaluating CT sensitivity in identifying the signs of pulmonary cystic fibrosis (CF). The chests of 39 patients (16 males and 23 females, mean age 19.1 years) were examined by CT: all patients had been given a clinical score according to Schwachman and Kulckzycki criteria. Thickened bronchial walls were observed in all cases, which are typical of peribronchitis. Bronchiectases were present in 87% of cases; their extent, pattern and localization were exactly shown on CT scans. Bronchoceles were seen on CT scans in 64% of patients; less frequent was the finding of atelectases and subpleural bullous emphysema. In a great number of patients (64% and 82%, respectively) pleural thickening and hilar adenopathy were demonstrated on CT scans. In conclusion, our results confirm CT as a more sensitive method than conventional radiography to identify and locate the signs of pulmonary CF. The early identification of the lesions is of high prognostic value, since the early detection and treatment of bronchoceles may prevent permanent bronchiectasis. PMID- 1896586 TI - [Radiologic study of the thorax using the digital method (FCR 101). Evaluation of various parameters as related to exposure]. AB - A computed radiography system with solid state detectors (FCR 101) was employed to evaluate the quality of digital images, with optimal and progressively lowered doses, in the study of the chest. Routine chest radiographs of in patients with no pathologic conditions of the chest were studied. The patients were divided into 3 groups: each patient in group A underwent two radiographs, one at 100% and the other at 50% exposure; patients in group B were imaged with 100% and 25% doses, and those in group C received 50% and 25% exposure. Several parameters were employed for image evaluation, and a value was given to each of them (1 = good, 2 = sufficient, 3 = insufficient). Upon comparison of the average values obtained, we observed that the digital technique allowed a most accurate and well defined representation of the examined parameters at 100% exposure dose and that a 50% reduction did not decrease the informative content in the least. A 25% reduction, however, determined a high degree of background noise and a subsequent, though slight, loss of information. PMID- 1896589 TI - [Progress in chronic headache]. PMID- 1896588 TI - [Ultrasonography and computerized tomography in the diagnosis of renal metastasis]. AB - The US and CT findings of renal metastases are described in a series of 26 patients. US findings were round or oval masses ranging in diameter from 1.5 cm to 8 cm (mean: 4.2 cm); in only 21.2% of cases lesion diameters were less than or equal to 3 cm. In most patients (84.8%) the metastatic lesions were hypo isoechoic, while in the extant cases they were either mildly hyperechoic or inhomogeneous. CT findings were round masses with variable diameters (1 cm to 8 cm; mean: 2.7 cm); in most cases (86.4%) lesions diameters were less than or equal to 3 cm. The latter finding was in significant disagreement with US results. CT densities were within the soft-tissue range, and always hypodense if compared to normal renal parenchyma in contrast-enhanced scans. Few cases of perirenal metastases were observed. US sensitivity was only 57%, much lower than that of CT; the latter method yielded no false negatives. CT showed metastatic lesions in patients with normal US findings; in 2 cases a greater number of lesions was detected with CT than with US. Our results are in substantial agreement with literature data, as far as US and CT findings are concerned; however, a lower incidence of bilateral cases was observed in our series than in previous reports. Our results support the primary role of CT in the detection of renal metastases thanks to its high sensitivity and to its allowing the simultaneous evaluation of other organs. PMID- 1896587 TI - [Fine needle aspiration biopsy (FNAG) guided with tomodensitometry of pulmonary and mediastinal masses. Personal experience]. AB - CT-guided fine-needle aspiration biopsy (FNAB) was performed on the patients with pulmonary or mediastinal masses to obtain material for cytologic/histologic diagnosis. Diagnostic accuracy and safety of the technique were evaluated in 75 patients affected with thoracic lesions still undiagnosed after thorough radiological and endoscopic investigations. The cytologic and/or microhistologic samples allowed a correct diagnosis to be made in 61 cases (81%), with no false positives and 7 false negatives (9%). The samples were inadequate for diagnostic purposes in 7 cases (9%). Specificity, sensitivity, and diagnostic accuracy were 68%, 76%, and 81%, respectively. No major complication was recorded and a case of asymptomatic pneumothorax resolved spontaneously within 48 hours. CT-guided FNAB of space-occupying lesions in the lung and mediastinum is therefore a rapid and valuable diagnostic tool and is quite safe when performed by skilled operators. PMID- 1896591 TI - [The radiologic manifestations of bronchiolitis obliterans]. AB - We reviewed the radiological findings in 19 patients suffering obliterans bronchiolitis, all of whom were classified as idiopathic obliterans bronchiolitis with organizing pneumonia. In most cases, above 80%, X-rays showed alveolar opacities in patches; other less frequent findings were the presence of an interstitial pattern and cavitation (10%). Radiological findings are not specific being most useful in posttreatment patient follow-up. PMID- 1896590 TI - [Aluminum absorption in the presence of normal kidney function: the effect of the pH]. AB - Aluminium is a toxic metal of known importance in patients with chronic renal failure on hemodialysis, with a gastrointestinal absorption modulated by several factors including gastric pH which modifies the solubility of Aluminium hydroxide and can increase its absorption. We studied twenty six patients with normal renal function: control (n = 13); presurgery (n = 8); postsurgery (n = 5) by an aluminium hydroxide absorption test (30 mg/kg); serum and urinary aluminium was determined as well as gastric pH and hematologic parameters at different time periods. It was observed that presurgery ulcer patients (pH mean = 2.09) increased serum and urine aluminium levels as well as aluminium/creatinine ratio in urine after the test, opposite to what occurs in the postsurgery group (pH mean = 5.78) in which such parameters were not significantly modified. No differences were found in hematological parameters between the two groups. Our results indicate that acid gastric pH seems to be a factor capable of increasing gastrointestinal absorption of aluminium hydroxide since its solubility and thus its disponibility is increased, and make a point on the risk of a prolonged administration of antacids containing aluminium in patients with normal renal function. PMID- 1896592 TI - [Hemoptysis: a prospective study of 108 cases in an emergency service]. AB - A prospective study is performed in 108 patients presenting hemoptysis who were attended in the emergency department. Final diagnosis was achieved in 89 cases (82.4%), being lung infections of tuberculous origin or not, neoplasias, and chronic obstructive lung emphysema the main observed etiologies. A low percentage of severe hemoptysis is found (5.6%). Diagnosis was obtained in 79.6% of patients by clinical history, physical exam, chest x-ray and ORL exam. Only 13.6% of patients who were not diagnosed in the Emergency department were later diagnosed by follow up and performance of complementary tests. Similarly, the lack of an initial etiological diagnosis had no repercussion, by itself, in a worse prognosis. Therefore, it is recommended to perform a single strict evolution control in patients with hemoptysis of unknown origin who present risk factors of lung neoplasia (male sex, age greater than 40 years, smoking greater than 45 packs/year). PMID- 1896593 TI - [The effect of continuous positive-pressure via the nose (CPAPn) on the ventilatory pattern]. AB - The modifications in the ventilation pattern when a continuous positive pressure is applied through the nose (CPAPn) in an acute form or by increasing pressures is evaluated in 13 normal subjects and 8 individuals presenting obstructive sleep apnea syndrome (OSAS). No significant modifications are observed in breathing frequency or breathing time when 5 and 10 cm of H2 are applied. It is concluded that this mechanism does not seem to be involved in the disappearance of hypercapnia which occurs in some patients with OSAS. PMID- 1896594 TI - [Hypersensitivity reactions to ethylenediamine]. AB - Most allergic reactions to aminophylline are caused by hypersensitivity to ethylendiamine. We present 3 asthmatic patients, 2 of whom had immediate allergic symptoms after the administration of aminophylline. The third patient presented generalized erythrodermia 24 hours after receiving aminophylline. In all three cases sensitivity to ethylendiamine was observed in skin testing. These patients can tolerate other theophylline preparations not containing ethylendiamine. PMID- 1896596 TI - [Interleukin-2 and adoptive immunotherapy: their biological aspects and clinical application in oncology]. AB - Interleukin-2 (IL2), as a modifier of the biological response, has been intravenously used in patients with advanced cancer associated or not to LAK cells or tumor infiltrating lymphocytes. In different neoplasias positive results have been obtained, being effective in melanoma and renal cancer. There are still, at present, many questions to be answered and multiple research lines are currently open. The association with other cytokines and new chemotherapy protocols grant new therapeutic possibilities. PMID- 1896595 TI - [Pulmonary hemorrhage as the initial manifestation of Behcet's disease]. AB - Pulmonary hemorrhage in Behcet's disease is exceptional. It usually presents as a hemoptysis and appears in advanced stages. A patient is described who sought medical care for oral and genital lesions, arthritis and progressive dyspnea. Analytical data showed anemia and chest X-ray revealed a bilateral interstitial pattern. A fiber bronchoscopy was performed which confirmed the existence of a diffuse pulmonary hemorrhage. Corticosteroid and azatioprine administration resolved the hemorrhage. Pulmonary hemorrhages in Behcet's disease are reviewed and in view of a available literature therapeutic possibilities are discussed. PMID- 1896597 TI - [Acute interstitial nephritis]. PMID- 1896598 TI - [The pleural line sign]. PMID- 1896599 TI - [Barrett's esophagus and omeprazole]. PMID- 1896600 TI - [Chronic tuberculous otitis media. An infrequent entity]. PMID- 1896601 TI - [An axillary abscess produced by Oerskovia turbata in an AIDS patient]. PMID- 1896602 TI - [Pure motor hemiparesis as the initial manifestation of a cerebral tumor]. PMID- 1896603 TI - [Primary malignant melanoma of the lung]. PMID- 1896604 TI - [Pneumomediastinum and Pneumocystis carinii pneumonia]. PMID- 1896605 TI - [The sleep apnea syndrome and auricular fibrillation]. PMID- 1896606 TI - [Iliopsoas bursitis as a cause of inguinal tumor formation]. PMID- 1896608 TI - Molecular analysis of germinal centre B cells. PMID- 1896607 TI - Cloning and expression of genomic DNA sequences coding for putative erythrocyte membrane-associated antigens of Plasmodium falciparum. AB - Genomic DNA fragments of Plasmodium falciparum generated by mung bean nuclease digestion were cloned in the lambda expression vector lambda JK2. The resulting library was screened with a rabbit antiserum raised against purified membranes of P. falciparum-infected erythrocytes and with a serum pool from immune humans from an endemic area of Liberia. Positive clones were rescreened with a series of human and monkey sera. Twelve selected clones were analysed in detail. Four of them corresponded to already described membrane-associated P. falciparum antigens. The other positive clones contained inserts which, according to the nucleotide sequence, Southern blot analysis and immunological characteristics, correspond to so far unknown antigens. PMID- 1896609 TI - Are Peyer's patch germinal centre reactions different from those occurring in other lymphoid tissues? PMID- 1896610 TI - The follicular dendritic cell: possible regulatory roles of associated molecules. PMID- 1896611 TI - Cellular interactions within the germinal centre. PMID- 1896612 TI - Understanding germinal centres. PMID- 1896613 TI - The germinal centre: a monastery or a bar? PMID- 1896615 TI - The initiation of germinal centre reactivity. PMID- 1896614 TI - Cellular interactions during the germinal centre response. PMID- 1896617 TI - Follicular dendritic cells in germinal centre development. PMID- 1896616 TI - The heterogeneity of follicular reactions. PMID- 1896618 TI - Significance of iccosomes in the germinal centre reaction. PMID- 1896619 TI - Cellular components involved in the germinal centre reaction. PMID- 1896620 TI - Memory B cells and germinal centres. PMID- 1896621 TI - The role of antigens, antibodies and immune complexes in the functional activity of germinal centres. PMID- 1896622 TI - Nature of the late potentials and F-ratio values in dogs. AB - There is controversy about the nature of the late potentials (F-waves and H reflexes) in dogs. This work has attempted to clarify the problem by comparing late potentials in eight intact and four chronically deafferented dogs. Pure H reflexes were recorded inconsistently from intact preparations at voltages below the threshold for the M-wave. At stimulation voltages giving maximum direct responses, there was no statistically significant difference between the amplitude and latency of the late potentials of the two groups. However, there was a tendency for the late potentials to be of larger amplitude and longer duration in intact preparations. Late potentials in intact preparations had a composite waveform consisting of both F-waves and H-reflex components. F-waves only were present in deafferented limbs, and their amplitude was proportional to the intensity of the stimulus. F-ratios could be calculated by using the latencies of the late potentials, because the F-wave did not have a longer latency than the H-reflex. The following reference values for the F-ratio are proposed: 1.954 +/- 0.086 when stimulating at the hock and 0.883 +/- 0.052 when stimulating at the popliteal fossa. PMID- 1896623 TI - Effects of the adjuvant DEAE-dextran and Staphylococcus aureus on the lymph pathways and filtering capacity of popliteal lymph nodes in sheep. AB - The effects of subcutaneous injections of the adjuvant DEAE-dextran and, or killed Staphylococcus aureus on the structure of the lymph pathways of popliteal lymph nodes in sheep were examined using light and electron microscopy and Microfil casts. Dextran with or without killed S aureus caused significant changes in the lymph pathways both within the node and outside it. However, killed S aureus alone did not. The changes included anastomoses among afferent lymph vessels and between afferent and efferent lymph vessels; proliferation of vessels around the node; joining of parts of the capsule and trabeculae to adjacent parenchyma with loss of parts of the subcapsular and trabecular sinuses; enlargement of medullary sinuses; and reduction of the number of reticular processes in sinuses throughout the node. These changes were accompanied by a reduced ability of the node to filter chicken red blood cells labelled with chromium-51 which were injected into an afferent lymph vessel. PMID- 1896624 TI - M cells in the rectum of calves. AB - The morphology of gut-associated lymphoid tissue and the ultrastructure of overlying lymphoepithelium of newborn and three-week-old conventionally raised calves were compared. In all calves patches of lymphoid nodules were found in the terminal rectum. In newborn calves lymphoid nodules in the submucosa with caps of lymphoid tissue in the lamina propria predominated. In three-week-old calves lymphoglandular complexes were as numerous as lymphoid nodules with caps. Scanning and transmission electron microscopical examination of superficial lymphoepithelium over caps and lymphoepithelium in epithelial diverticula of lymphoglandular complexes revealed groups or single cells morphologically resembling M cells, but with widely varying apical processes. To investigate whether these putative M cells in rectal lymphoepithelium internalise and transport macromolecules across the epithelial barrier, ferritin was injected into the rectum of three-week-old calves. Eighty to 150 minutes after exposure ferritin was detected in cells resembling M cells. Thus these cells ought to be considered as M cells. It may be hypothesised that gut-associated lymphoid tissue with specialised lymphoepithelium in the rectum of calves provides a route for the uptake of antigen. PMID- 1896625 TI - Effect of chemicals on glutathione peroxidase of chick liver. AB - Chick liver glutathione peroxidase activity was separated into selenium-dependent and selenium-independent enzyme fractions and the effects of chemicals on the activities of each fraction were examined. Clofibrate induced the selenium dependent enzyme, while phenobarbital, butylhydroxyanisole and trans-stilbene oxide elevated selenium-independent peroxidase activity. A third enzyme, which showed glutathione peroxidase activity toward both hydrogen peroxide and cumene hydroperoxide, was found. PMID- 1896626 TI - Antigenic diversity of Cowdria ruminantium isolates determined by cross-immunity. AB - Antigenic diversity in five stocks of the tick-borne rickettsia Cowdria ruminantium, the causal agent of heartwater disease of ruminants, was studied by cross-immunity trials in goats and sheep. Complete absence of cross-protection was found only between the Kumm and Kwanyanga stocks, and in all other combinations there were various degrees of cross-immunity. Immunological strain differences were more pronounced in goats than in sheep. PMID- 1896627 TI - Limited heterogeneity between strains of Eimeria tenella isolated from Britain and Bangladesh. AB - Single-oocyst-derived field strains of Eimeria tenella isolated from Rugby in the United Kingdom (E tenella R) and from Mymensingh and Dhaka in Bangladesh (E tenella M and D, respectively) and a laboratory strain (E tenella, Houghton, H) were compared by isoenzyme electrophoresis, reactivity with antisporozoite monoclonal antibodies and, for some pairs of strains, cross-protection in vivo. The three field strains conformed to one zymodeme with respect to six isoenzymes. For glucose phosphate isomerase (GPI) all field strains were characterised by GPI 9. A panel of six different monoclonal antibodies raised against sporozoites of E tenella H did not discriminate between strains by titration in an immunofluorescence assay against air-dried, acetone fixed sporozoites. In cross protection experiments involving immunisation and challenge of young chickens, two immunisation schedules were used which, after homologous challenge, provided complete immunity either by the criterion of oocyst output, or by the criterion of weight gain (and more than 94 per cent protection by the criterion of oocyst output). While strain heterogeneity was minimal in the former situation, there was poor cross protection between some strains in the latter case. Under those conditions, heterologous challenge with E tenella M resulted in dysentery and in significantly (P less than 0.05) increased oocyst output and decreased weight gain. The results suggested that E tenella M was immunologically superior to E tenella R and H strains. The results show that a limited degree of immunogenic variability exists between these strains of E tenella and that, unless homologous strain immunity is complete by the criterion of oocyst output, challenge with heterologous strains may result in depressed weight gain. PMID- 1896628 TI - Description of the effects of a single gene which inhibits the normal metabolic response of newborn lambs to exogenous noradrenaline. AB - A group of newborn Scottish Blackface lambs previously selected for low cold resistance failed to show the normal metabolic response to subcutaneous injection of exogenous noradrenaline. A subsequent study showed this failure to be due to a single major gene. Further studies on the thermogenic and physiological responses and on the inheritance of the trait, are described here. Two intercross matings between non-responders produced responder lambs indicating that the gene is not recessive. The increases in metabolic rate and rectal temperature after injection of noradrenaline were much greater in responder than in non-responder lambs (P less than 0.001), as were the increases in heart rate and respiration rate (P less than 0.001). Dissected brown adipose tissue from non-responders was apparently normal and indistinguishable from brown adipose tissue from responders. Although there was no apparent effect of the gene on birthweight or survival, survival under normal field conditions may be affected. PMID- 1896629 TI - Some cutaneous responses to mitogen injection in sheep, with special reference to eosinophil leucocytes. AB - Research in laboratory animals suggests that eosinophil numbers in some cutaneous reactions may reveal inherent differences in resistance to parasite infection. An intradermal injection with 10 microgram of the mitogen phytohaemagglutinin, followed by counting eosinophils in the deep dermis of skin biopsies removed 24 hours later, appears to be a practical and reproducible way of comparing the ability of individual sheep to marshal eosinophils in a tissue. This procedure will allow study of the relationship between eosinophil response and resistance to parasite infection in sheep. PMID- 1896630 TI - Mechanical properties of the isolated equine trachea. AB - In order to study the in vitro mechanical properties of the equine trachea submitted to the compressive pressures observed in vivo, the pressure-volume relationship was determined in intra- and extra-thoracic tracheal segments taken post mortem from 29 healthy horses (one to 15 years old; 352 to 651 kg). At the same time, the cross-sectional lumen area (X-SA) at the mid-point of the segment was measured using a slit-lamp transillumination and photographic measurement by endoscopy. The tracheal specific compliance (Cs) as well as the relative changes in X-SA and in the sagittal and transverse diameters, for intraluminal pressures from 5 to - 5 kPa, were calculated. The extrathoracic tracheal Cs was 0.060 +/- 0.002 kPa-1 and, at an intraluminal pressure of - 5 kPa, X-SA was reduced to about 73 per cent of its resting value. The intrathoracic segments were more compliant and, at similar compressive pressure, their X-SA was more reduced. These data show that the equine tracheal compliance is high and suggest that the increase in pulmonary resistance observed during strenuous exercise may be partly explained by a partial tracheal collapse. PMID- 1896631 TI - Cow-calf behaviour in relation to first suckling. AB - For the newborn calf, the length of time between birth and when (and if) it manages to obtain its first suckle plays an important role in the acquisition of passive immunity. In a study of 21 pairs of dairy cows and their calves, loose housed in individual calving boxes, the calves suckled for the first time at a median of four hours, nine minutes after birth. Nineteen suckled within 12 hours, with a range between 50 minutes and 11 hours, 44 minutes. Calves that were active early usually suckled early. However, irrespective of the start of a calf's activities, long pauses while teat seeking played a decisive role in the time of the first suckling. Factors which affected the periodicity and length of these pauses would therefore greatly influence the time of the first suckling. PMID- 1896632 TI - Regulation of mitogen- and TCGF-induced lymphocyte blastogenesis by prostaglandins and supernatant from equine embryos and endometrium. AB - Immunosuppressive substances which interfere with lymphocyte blastogenesis are released in vitro by embryos and endometrium from mares in early pregnancy. Immunosuppression was not evident when tissues were cultured in the presence of indomethacin (a prostaglandin-synthesis inhibitor). Various prostaglandins (PGs) were added to equine lymphocytes and lymphocyte proliferation was measured after the addition of concanavalin A (Con A) or phytohaemagglutinin A (PHA). PGE2 and PGF2 alpha inhibited Con A-induced blastogenesis down to final concentrations of 1.8 x 10(-9) M and 1.3 x 10(-6) M, respectively. Other PGs tested (6-keto-PGF1 alpha and 13,14-dihydro-15-keto-PGF2 alpha) did not affect Con A-induced blastogenesis. PHA-induced blastogenesis was inhibited by concentrations down to 1.8 x 10(-9) M PGE2, 3.3 x 10(-7) M PGF2 alpha and 2.8 x 10(-4) M 6-keto-PGF1 alpha. At all concentrations, 13,14-dihydro-15-keto-PGF2 alpha only slightly reduced PHA-induced blastogenesis. Therefore, PGE2 was the only prostaglandin tested which, at physiological concentrations, significantly inhibited incorporation of [3H] thymidine. The mechanism of PGE2-mediated suppression was studied by adding PGE2 and T cell growth factors (TCGF) to TCGF-responsive lymphocytes. PGE2 reduced the TCGF-mediated blastogenic response in a dose dependent manner. Furthermore, culture supernatant from embryos and endometrium from 14-day pregnant mares inhibited lymphocyte blastogenesis induced by TCGF. These results show that PGE2 interferes with lymphocyte blastogenesis by TCGF dependent mechanisms. It is suggested that the PGE2 present in the uterus of the early pregnant mare may be one of the factors involved in immunosuppression at the time of maternal recognition of pregnancy. PMID- 1896633 TI - Interleukin-1-like activity in synovial fluids and sera of horses with arthritis. AB - Synovial fluid samples of horses with osteoarthritis were investigated to detect interleukin-1 (IL-1) activity which could contribute to the disease pathogenesis. Of the 32 samples tested, 12 (37.5 per cent) showed an augmented phytohaemagglutinin induced proliferation of C3H/HeJ mouse thymocytes. Positive results were also seen in horses with infected arthritis, osteochondritis, traumatic arthritis and undefined synovial effusions. Normal synovial fluid and sera from all groups failed to show any detectable IL-1 activity. Fractionation of synovial fluid showed that the IL-1 activity was in the 15 to 20 Kd fractions. In the absence of mitogen, synovial fluid failed to stimulate thymocytes and did not stimulate the growth of an interleukin-2 (IL-2) dependent CTLL cell line, but synovial fluid stimulated IL-2 release by mouse spleen cells incubated with suboptimal doses of lectin. Evidence of an IL-1 inhibitor in synovial fluid from osteoarthritic horses was provided by ultrafiltration experiments and by the inhibitory activity of synovial fluid at particular dilutions in the thymocyte assay. The presence of IL-1-like activity could be relevant in the pathogenesis of arthritis in horses. PMID- 1896634 TI - Development of techniques to analyse the formation of HIV provirus in primary human macrophages. AB - The formation of provirus is an important early event in the life cycle of a retrovirus. We describe a system using PCR for the analysis of this process in primary human macrophages infected in vitro with HIV. We show that products of the first template switch can be detected within 8 h after infection at low multiplicity. The methods described provide a rapid assay of infection with HIV and can be applied in the investigation of a number of aspects of HIV replication in macrophages. PMID- 1896635 TI - Latent infection of epidermal Langerhans cells in HIV-positive individuals. AB - Epidermal cell suspensions obtained from 3 symptom-free HIV-positive individuals were cultured and marked with monoclonal antibodies for the HIV proteins p15, p24 and gp120 in the alkaline phosphatase anti-alkaline phosphatase staining technique. For 2 individuals, cells were positive after 3 days in culture, and for the third, after 4 days. Supernatant from one of the cultures infected allogeneic peripheral blood mononuclear cells. We conclude that epidermal Langerhans cells from symptom-free HIV-positive individuals are latent-infected and are able to produce and release HIV. PMID- 1896636 TI - Effect of HIV on antigen presentation by dendritic cells and macrophages. AB - The antigen-presenting function of dendritic cells (DC) and macrophages (MO) following infection with HIV in vitro was examined. Using non-infected cells, DC, but not MO, stimulated primary proliferative responses in allogeneic lymphocytes in the mixed leukocyte reaction. Both DC and MO stimulated secondary responses to influenza virus and to tetanus toxoid in autologous T lymphocytes. After exposure of DC and MO to HIV1 in vitro for 2 days, 27% of DC but less than 1% MO became infected as assessed by in situ hybridization. DC were blocked in their capacity to stimulate responses to alloantigens or to the recall antigens. By contrast, MO retained the ability to stimulate responses to the recall antigens. Similar effects during in vivo infection would allow activated T-cell clones to respond to antigens presented by MO early in infection. However, any loss of activated T cells might prove cumulative and damaging in the absence of an effective DC recruitment mechanism for resting T cells. PMID- 1896638 TI - Target cells for HIV in the central nervous system: macrophages or glial cells? AB - Infection of foetal or embryonic brain cells and cell lines from human astrocytomas and gliomas with HIV1 derived from T-lymphoma cultures leads to the expression of HIV in about 1 to 2% of the cells in culture. Single-cell cloning of astrocytoma cells shortly after infection resulted in the establishment of persistently HIV1-infected cell lines. These cultures were characterized by low production of virus and moderate intra- and extracellular expression of structural proteins. However, high expression of the nef regulatory protein was found. The virus could be rescued by cocultivation with T cells and primary macrophages giving rise to typical syncytia formation. In contrast to infection with HIV-infected T-lymphoma lines, cocultivation with HIV1-infected primary macrophages or monocytic cell lines induced a reduction in the growth of astrocytes and failed to induce productive infection. These in vitro observations support the hypothesis that astrocytes and glial cells may be a reservoir for HIV in the central nervous system and that macrophages may not carry the virus to the brain, but rather may be infected in the brain after having penetrated the blood brain barrier. PMID- 1896637 TI - Trypsin-resistant gp120 receptors are upregulated on short-term cultured human epidermal Langerhans cells. AB - The CD4 molecule is known to be the preferential receptor for the HIV1 envelope glycoprotein. Epidermal Langerhans cells (LC) are dendritic cells which express several surface antigens, among them the CD4 antigens. LC infection was suggested when these cells were seen to present buddings coincident with membrane thickening of roughly 100 nm in size. These buddings were similar in ultrastructural aspect to HIV buddings on in vitro infected promonocytic cells (U937). To clarify the exact role of CD4 molecules in LC infection induced by HIV1, we investigated the possible involvement of between native and recombinant HIV1 gp120 and the LC surface. We also assessed the expression of CD4 molecules on LC membranes dissociated by means of trypsin from their neighbouring keratinocytes. The cellular phenotype was monitored using flow cytometry. We show that human LC can bind the viral envelope protein and that this binding does not depend on CD4 protein expression. The amount of surface bound gp120 was not consistent with the amount of CD4 antigens present on LC membranes. The gp120 binding sites on LC in suspension appear to be typsin-resistant while the CD4 antigens (at least the epitopes known to bind HIV1) are trypsin-sensitive. A burst of gp120 receptor expression was detected on 1-day cultured LC while the CD4 antigens disappeared. These findings lead to the logical conclusion that the binding of gp120 is due to the presence of a LC surface molecule which is different from CD4 antigens. PMID- 1896639 TI - HIV receptors within the brain: a study of CD4 and MHC-II on human neurons, astrocytes and microglial cells. AB - We have investigated the level of expression of CD4 and MHC-II antigens on CNS cells and compared it to that on monocytes. MHC-II antigens were expressed spontaneously on cultured astrocytes and monocytes, whereas they were detected only after IFN gamma stimulation of microglial cells. In vitro, CD4 receptor was present on monocytes but not on neurons, astrocytes or microglial cells. In normal brain, CD4 antigen was expressed on perivascular microglial cells, a specialized microglia expressing monocytic markers, whereas in HIV1-infected brain, CD4+ cells were numerous and scattered throughout the whole parenchyma. These CD4+ macrophages may be HIV1-infected monocytes which have crossed the blood-brain barrier after infection, or perivascular microglial cells infected by HIV1-infected blood lymphocytes or five virions. PMID- 1896640 TI - Infection of granulocyte/monocyte progenitor cells with HIV1. AB - In order to study whether cytopathic HIV1 infection of haemopoietic progenitor cells is involved in the derangement of haemopoiesis in patients with HIV1 infection, we infected enriched progenitor cells with HIV1, by addition of viral inoculate supernatants from HIV1-infected peripheral blood mononuclear cells or by coculture with HIV1-infected monocytes/macrophages. Progenitor cells were seeded into colony assays and single colonies were chosen for HIV1 mRNA determination by in situ hybridization. Growth of progenitors was not affected by infection. However, up to 42% of colonies of pluripotent progenitor cells (colony forming unit/granulocyte-erythrocyte-monocyte; CFU-GEM) and committed progenitor cells CFU/granulocyte-monocyte (CFM-GM) contained HIV1 mRNA-expressing cells. In addition, we studied HIV1 infection of progenitor cells from the bone marrow of 6 patients with AIDS or AIDS-related complex. Two patients were negative, two had a few colonies expressing HIV1 mRNA in a minority of cells, and in the remaining two, up to 11% of CFU-GM contained HIV1-expressing cells. Thus, infection of progenitor cells with HIV1 was achieved experimentally in vitro and occurs in vivo. However, growth of progenitors after in vitro infection continues and therefore HIV1 infection does not seem to contribute directly to the reduced incidence of haemopoietic progenitor cells in vivo. PMID- 1896641 TI - In situ immunophenotype of macrophages and lymphocytes in granuloma formation of tuberculous lymphadenitis in HIV-infected and immunocompetent patients. AB - The phenotype of inflammatory cells in lymph nodes from 16 patients with culture proven tuberculous lymphadenitis were examined by histological and immunohistochemical techniques. Eight patients were suffering from a symptomatic HIV1 infection and 8 patients were immunocompetent individuals without positive HIV1 serology. In addition, the lymph nodes of 2 AIDS patients with Mycobacterium avium-intracellulare infection were examined using the same techniques. Characteristic granulomas with or without caseation were observed in the 8 immunocompetent and the 4 HIV1-infected patients with less marked lymphopenia of CD4+ peripheral blood lymphocytes (PBL). In lymph nodes from the other HIV1 infected patients with more severe depression of CD4+ PBL, no epithelioid cell formation was present; instead, foamy macrophages were found. The phenotype of the macrophages underwent progressive changes in parallel with the decreasing numbers of CD4+ PBL. Foamy macrophages in M. avium-intracellulare infection exhibited remarkable erythrophagocytotic activity and may represent an end-stage phenotype. They were positive for S100 protein and did not produce lysozyme or alpha-1-antichymotrypsin. They lost the antigen which was detected by monoclonal antibody Mac387 whereas positivity for HLA-DR, CD68 and KI-M8 was preserved. While many lymphocytes expressed CD25 (IL2 receptor) in cases with typical granulomas, there was no such CD25 expression in cases without epithelioid cell formation. Although granulomas have been produced in experimental animals independently of cell-mediated immune mechanisms, our results suggest that T-cell functions are necessary for epithelioid granuloma formation in human tuberculosis. PMID- 1896643 TI - Morphine stimulates HIV replication in primary cultures of human Kupffer cells. AB - Intravenous drug abusers represent a high risk group for HIV infection in Europe and North America. Although the use of blood-contaminated needles undoubtedly constitutes the main factor of transmission of the virus, an effect of the drug itself either on the immune system or on virus replication, thus favouring the initiation of the infection, may not be excluded. We have formerly established that primary cultures of human Kupffer cells (KC) are permissive for HIV1. In this paper, we describe the effect of morphine hydrochloride on the multiplication of different isolates of HIV1 in cultured human KC. KC were obtained by dissociation of human liver fragments with collagenase and purified by centrifugal elutriation. Five-day-old KC were infected with HIV1; at different intervals, the production of virus was quantitated by the reverse transcriptase activity associated with the particles present in the culture medium. In primary cultures of KC preincubated for 48 h and maintained in the presence of morphine, the production of viral particles was increased. This enhancing effect was found with 3 different HIV1 isolates. Treatment of KC with morphine prior to infection was not required for the stimulation to take place, which indicated that the enhancing effect was not related to a more efficient adsorption of the virus to the KC plasma membrane. Stimulation of HIV1 production was observed for all the concentrations of morphine used (0.05 to 0.5 mg/ml). These results, if confirmed in vivo, may shed new light on the risk factors related to the intravenous administration of heroin. PMID- 1896642 TI - Monocyte/macrophage giant cell disease in SIV-infected cynomolgus monkeys. AB - A non-opportunistic, generalized giant cell disease (GCD) was found in 12 out of 25 (48%) cynomologus monkeys infected with SIVsm. Most organs were affected notably the lymph nodes (LN), spleen, gut, liver, lungs and CNS. The multinucleated GC varied considerably in cell size and in the number and cytoplasmic distribution of the nuclei. Immunohistochemically most GC expressed SIV antigens and markers of mononuclear phagocytes (CD68), CD4 and also occasionally the T-cell markers CD45RO, CD43 and CD2. Monkeys with GCD had more pronounced immunosuppression with lower CD4-cell counts, more often demonstrable SIV antigen in the blood and LN and had been infected for a longer time period, as compared to monkeys without GCD. These findings show that SIV infection in cynomolgus monkeys is frequently associated with extensive formation of multinucleated GC of macrophage origin, which appears to be related to the pathogenesis of the infection and the degree of immunosuppression. PMID- 1896644 TI - HIV1 infection of human monocytes and macrophages promotes induction or translocation of NF-KB-related factors. AB - In 1991, we demonstrated, using electrophoretic mobility shift assays, that 3 different factors (termed B1, B2 and B3) with affinity for the KB-enhancer target sequence were specifically detected in nuclear extracts from HIV1-infected monocytes and macrophages. The B2 factor was induced in the nuclei of these cells only upon HIV1 infection. The B3 factor was only slightly evident in nuclei of uninfected cells but was readily detectable in nuclei of infected monocytes. Its expression remained very low in nuclei of HIV1-infected macrophages. In this paper, we demonstrate that the B2 factor is expressed in the cytosol of monocytes and macrophages as a DNA-binding protein, indicating that it is not associated with an inhibitor (IKB). This factor remained clustered in the cytosol and was translocated to the nuclei only after HIV1 infection. The B3 factor is detected in the cytosol only when cells are HIV1-infected. The role of HIV1 infection in the expression and the translocation of these factors is discussed. PMID- 1896645 TI - Induction of NF-kappa B during monocyte differentiation is associated with activation of HIV-gene expression. AB - Cells of the monocyte-macrophage lineage are important targets of HIV infection. We report here that the phenotypic differentiation of monocyte cell lines induced by phorbol esters or tumour necrosis factor alpha (TNF alpha) is associated with expression of nuclear factor kappa B (NF-kappa B). In parallel with such differentiation, HIV transcription, monitored using an HIV long terminal repeat reporter gene construct, is activated in such cells under the influence of enhanced NF-kappa B expression. Also, in a promonocyte cell line chronically infected with HIV, NF-kappa B expression and HIV transcription were enhanced on stimulation with phorbol ester or TNF alpha. Thus, stimulation of monocyte cell lines by phorbol esters or TNF alpha induces cell differentiation and activates HIV transcription. Such a process may have fundamental implications in AIDS pathogenesis in vivo and may be important in disease progression induced by opportunistic infections directly or indirectly involving macrophages. PMID- 1896646 TI - TGF-beta: upregulator of HIV replication in macrophages. AB - TGF-beta at physiological concentrations, when added to monocyte-derived macrophages following HIV1 infection, has an enhancing effect upon the rate of virus production. This effect is observed with the monocytotropic isolate ADA, as well as with HIV1 IIIB, which poorly replicates in macrophages. PMID- 1896647 TI - Macrophages play a key role in the evolution of HIV infections. PMID- 1896648 TI - Macrophages as target cells for HIV. November, 1990, Le Bischenberg, France. PMID- 1896649 TI - Lack of HIV tat-gene amplification in blood monocytes compared to T lymphocytes. AB - T-lymphocytes (T-Ly) and monocytes/macrophages are thought to be the main in vivo targets for HIV 1. We previously demonstrated, using the polymerase chain reaction (PCR), that HIV provirus could be detected in 20 out of 21 T-Ly samples and 13 out of 21 monocyte samples from HIV 1-seropositive individuals, with at least gag, env or LTR primers. In the present study, we wanted to find out whether the HIV 1 tat gene could be detected in 14 of these circulating monocyte and T-Ly samples. The tat primers were chosen in order to amplify the overall second exon of this regulatory gene. This new set of primers could not detect HIV provirus in monocytes but it did in T-Ly, among cells previously shown to be positive with one of the other 3 primer pairs. Further molecular studies should help characterize these probable monocytotropic variants and elucidate their contribution to HIV pathogenesis. PMID- 1896650 TI - Replication of human immunodeficiency virus type 1 in primary cultured placental cells. AB - The role of placental cells in transplacental transmission of human immunodeficiency virus type 1 (HIV 1) was investigated. Placental macrophages and trophoblasts, which together represent the main cell components of the placenta, were cultivated separately and then compared to foetal monocyte-derived macrophages for susceptibility to HIV 1 infection. Placental macrophages treated with granulocyte-macrophage colony-stimulating factor (GM-CSF) were less easily infected with HIV 1 than were GM-CSF-treated foetal monocyte-derived macrophages. HIV 1 replication in cocultures consisting of infected placental macrophages together with a highly HIV 1-permissive cell line (CEM) was detected persistently for at least 6 weeks by reverse transcriptase assay, even though placental macrophages expressed no detectable CD4 receptor, as indicated by indirect immunofluorescence. HIV 1-specific DNA sequences were also detected in infected placental macrophages. Trophoblasts exhibited no detectable CD4 expression and did not support the replication of HIV 1, although low levels of HIV 1-specific DNA sequences could be detected in infected trophoblasts. Placental macrophages or trophoblasts (or both) may thus play an important role in transplacental HIV 1 transmission. PMID- 1896651 TI - [Epidemiology of major organ damage due to arteriosclerosis]. PMID- 1896652 TI - [Arteriosclerosis of organ arteries]. PMID- 1896653 TI - [Cerebrovascular disorders]. PMID- 1896654 TI - [Coronary artery disease with arteriosclerosis obliterans of lower limb]. PMID- 1896655 TI - [Involvement of intestinal branches with coronary arteriosclerosis]. PMID- 1896656 TI - [Aortic aneurysm]. PMID- 1896657 TI - [Transesophageal Doppler echocardiographic measurement of cardiac output using mitral anulus method]. AB - The method of measuring cardiac output with transesophageal pulsed Doppler two dimensional echocardiography was developed and validated by comparison with the thermodilution technique in 65 adult patients. With the use of transesophageal four-chamber view, the Doppler sample volume was placed in the center of the mitral ring and the mitral flow velocity-time integral was obtained through planimetric measurements of the mitral flow velocity curve. The diameter of the mitral valve anulus was measured at the time of peak rapid filling flow velocity, and the cross-sectional area of the mitral valve anulus was calculated, assuming a circular shape. Doppler-determined cardiac output was calculated by using the following formula: Cardiac output [1.min-1] = pi (D [cm] /2)2.MFVI [cm].heart rate [bpm].10(-3), where MFVI is mitral flow velocity-time integral, and D is the diameter of the mitral valve anulus. There was a weak correlation between thermodilution and Doppler measurements of cardiac output (r = 0.64, p less than 0.01), while a good correlation was observed between percent changes in thermodilution-derived cardiac output and those in Doppler-determined cardiac output (r = 0.92, p less than 0.01) during different loading conditions. It has been suggested that this method may be useful for assessing relative changes in cardiac output during short time periods. PMID- 1896658 TI - [Study of influence of respiratory rate to airway resistance in patients with pulmonary emphysema]. AB - Application of the panting method is very difficult for patients with pulmonary emphysema (PE). We attempted to measure airway resistance (Raw) during quiet breathing and changing respiratory rate step by step in patients with PE using a pressure-type body plethysmograph system (BX-82) correcting measured values by temperature and humidity. Influence of the respiratory rate to Raw was studied at 0.5l/sec of inspiratory and expiratory flow. Whenever the respiratory rate was going up, the Raw increased in spite of the increase of the thoracic gas volume. Raw (2Hz) was about one and a half times as high as Raw (quiet breathing). On the other hand, when the respiratory rate was going up, elevation of the peak flow was always able to be recognized. It seemed that the state of the airway varied during the panting method. The Raw measured during 0.5 Hz breathing (nearly quiet breathing) had small variability. Because the airway state during 0.5 Hz breathing was nearly the same as that during quiet breathing, measurement of Raw (0.5Hz) can be regarded as a practical method in patients with PE. PMID- 1896659 TI - [Intracoronary administration of ergonovine maleate for detecting vasospastic angina; one dose method]. AB - Coronary spasm is an important etiologic mechanism in the pathogenesis of myocardial ischemia. Provocative test of coronary spasm during coronary arteriography is clinically useful. The ergonovine test has gained widespread use, and we have examined the efficacy and safety of intracoronary ergonovine application with a fixed dose of 16 micrograms. We studied 119 patients undergoing coronary arteriography. Coronary spasm was induced in 34 cases by intracoronary administration of 16 micrograms of ergonovine maleate. Coronary spasm was readily resolved by intracoronary administration of isosorbide dinitrate. None of the cases negative to the intracoronary ergonovine applications could be induced by additional systemic administration of 0.4 mg of ergonovine. Side effects of ergonovine such as elevation of blood pressure, headache and chest symptoms were infrequent in the intracoronary ergonovine test. We conclude that our method of intracoronary ergonovine application is sensitive and safe for the diagnosis of coronary spasm. PMID- 1896660 TI - [A comparison of sudden near maximal exercise test (dash method) and Bruce protocol for pediatric patients]. AB - We examined 24 pediatric patients to evaluate the usefulness of sudden near maximal exercise test (dash method), where the subjects began to run at Bruce protocol of the last stage. 1) No considerable differences between two protocols were found in maximal oxygen consumption (V O2max), maximal heart rate (HRmax), maximal systolic blood pressure, and findings of electrocardiography. 2) The sudden maximal exercise test could be completed during a shorter period compared to Bruce protocol. 3) The sudden maximal exercise protocol reached 84% of HRmax and 47% of V O2max at one minute after the onset of the protocol, and produced 96% of HRmax and 89% of V O2max at two minutes after the onset. We considered that sudden maximal exercise protocol was useful to obtain a response similar to Bruce protocol at maximal exercise within a short period. We have to pay attention to the safety of the patients because their cardiopulmonary response to sudden maximal exercise protocol is dramatic. PMID- 1896661 TI - [Clinical studies of 16 cases of carcinomatous pericarditis]. AB - We studied the effects of local therapy on cardiac tamponade caused by carcinomatous pericarditis in 16 cases. Five out of 16 cases (drainage group) received treatment by only drainage of pericardial effusion, and the remaining 11 cases (infusion group) had local infusion of antineoplastic agents into the pericardium after drainage. The median survival time was 16 weeks in the infusion group and 19 weeks in the drainage group. There was no statistically significant difference. Reaccumulation of pericardial effusion was recognized in 3 patients in the drainage group (60%), and in 3 patients in the infusion group (18%). Our conclusion was that local infusion had no effect on prolongation of the survival time, but had a suppressive effect on reaccumulation of pericardial effusion. PMID- 1896662 TI - [Influence of Lp(a) on restenosis after coronary angioplasty]. AB - We clarified the relationship between lipoprotein (a) concentration and restenosis after coronary angioplasty (PTCA). The lipoprotein (a) concentration in patients with restenosis after PTCA was significantly higher than in patients without restenosis after PTCA (33.0 +/- 19.8 mg/dl vs 19.1 +/- 17.4 mg/dl, p less than 0.05]. Moreover, patients with a lipoprotein (a) concentration of more than 30 mg/dl had a high rate of restenosis after PTCA. Restenosis after PTCA is related to lipoprotein (a) concentration. PMID- 1896663 TI - [Quantitative analysis of myocardial fibrosis in myocardial biopsies--a comparison between computer analysis and point counting method]. AB - To select an appropriate method to analyze quantitatively myocardial fibrosis in myocardial biopsies, two methods, the computer analysis and the point-counting method observed at magnifications of x200 and x400, were compared. Our targeted points of examination were the accuracy and reproducibility of these methods. Twenty patients (10 with dilated cardiomyopathy and 10 with hypertrophic cardiomyopathy) were randomly selected, and the percent area of myocardial fibrosis in myocardial biopsies obtained from the right ventricular septum was measured by both the computer analysis and the point-counting method. Two observers measured the same area twice on the different days, independently. In the area of analysis, the endocardium was excluded to avoid the observer's bias. By comparing the data obtained from two observers, it was shown that the point counting method tended to give a larger mean value and standard deviation than the computer analysis method, but that the latter indicated better reproducibility than the former. Our result showed that the degree of myocardial fibrosis varied according to methods of analysis and observer's experiences. It is recommended that the comparison of myocardial fibrosis should be made only when the methods of analysis of fibrosis are identical. PMID- 1896664 TI - [An autopsy case of adult respiratory distress syndrome (ARDS) with peculiar histopathological features modified by a positive end-expiratory pressure (PEEP) therapy]. AB - A case is reported of adult respiratory distress syndrome(ARDS) combined with barotrauma due to positive end-expiratory pressure (PEEP) therapy. The patient was a 32-year-old woman with fulminant hepatitis, type B, who died of ARDS 22 days after the onset of the illness. The autopsy revealed extraordinary heavy lungs (left: 923g, right: 985g) with edema in the peripheral part and marked emphysematous changes in the central part near the hili. Histologically, scattered foci of intra-alveolar organization and interstitial fibrosis with hemorrhage were observed, which might have been the result of the proceeding pneumonia. The emphysematous lesion seen in this case was peculiar and not like any type of of ordinary pulmonary emphysema. Judging from the strange, sharply demarcated emphysematous lesion with marked destruction of alveolar structure, and the good preservation of the alveolar structure in the edematous lesion, the emphysematous lesion might be barotrauma which was induced by PEEP therapy on top of pneumonia. PMID- 1896665 TI - [A case of cardiomyopathy due to allergic bronchopulmonary aspergillosis]. AB - We report a rare occurrence of cardiomyopathy associated with allergic bronchopulmonary aspergillosis (ABPA). A 49-year-old man with a history of bronchial asthma was referred to the Matsuyama Red Cross Hospital for evaluation of the abnormal shadow on his chest X-ray. Laboratory examination showed blood eosinophilia and marked elevation of serum IgE concentration and IgE antibody to A fumigatus. The immediate and late skin reactivities to A fumigatus antigen were both positive. The diagnosis of ABPA was made. Treatment using prednisolone was effective in ameliorating the symptoms. However, he was admitted again due to dyspnea, edema and anorexia 6 months later. Chest X-ray, ECG, UCG and scintigraphy suggested severe cardiac failure. The clinical diagnosis of hypertrophic cardiomyopathy, and the pathohistological diagnosis of endomyocardial fibrosis were made by cardiac catheterization and biopsy of endocardium. Retrospectively, cardiomegaly had gradually increased during the past several months while peripheral blood eosinophilia had continued. All these data strongly suggested that eosinophilia due to ABPA might cause severe cardiac damage. PMID- 1896666 TI - [A case of Bochdalek hernia in an adult with volvulus of the stomach and hypopotassemia]. AB - Gastric volvulus is a rare disease. We recently encountered a gastric volvulus associated with Bochdalek hernia and severe hypopotassemia. A 32-year-old woman experienced epigastric pain and recurrent vomiting. The changes of the electrocardiogram in this patient (K1.8mEq/l) were inverted T wave and ST depression. She was diagnosed as having gastric volvulus associated with Bochdalek hernia by chest X-ray films, contrast radiography of the upper digestive tract and thoraco-abdominal CT scans. Symptoms did not disappear with the administration of conservative therapy. At laparotomy, the stomach was rotated around its mesenteric axis in the sagittal plane. After operative repair, symptoms disappeared, and serum potassium level returned to normal. Gastric volvulus is rather easily diagnosed if its existence is kept in mind. PMID- 1896667 TI - [Evaluation of tumor vascularization in primary lung cancer by transesophageal color Doppler echography]. AB - A 63 year-old male with primary lung cancer, was examined by transesophageal color Doppler echography (TEE). TEE revealed metastatic lymph node adjacent to the root of the right pulmonary vein. Direct invasion to the left atrium was neglected because of the finding that the left atrial wall was fluctuating according to cardiac movements. TEE also visualized a tumor vessel in which peak velocity of the flow was high, 1m/sec. The resected specimen showed that the tumor vessel had originated from the bronchial artery in the metastatic lymphnode. High velocity flow in the tumor by transesophageal Doppler analysis is highly indicative of malignancy. Doppler analysis in the tumor vessel might be useful in tissue characterization of the lymphnode in primary lung cancer. PMID- 1896668 TI - [A case of mitral stenosis developing infective endocarditis 18 months after PTMC]. AB - We presented here a case of mitral stenosis developing infective endocarditis 18 months after PTMC. A 33-year-old male was admitted to our hospital for the evaluation of mitral stenosis with signs of congestive heart failure. The use of PTMC was adequately indicated based on the data of previous cardiac catheterization and was successfully performed. The post-operative clinical course was good leaving only slight mitral regurgitation demonstrated by post valvuloplasty LVG. About 18 months after PTMC, the patient developed a high fever and erythema with tenderness on his leg, so he was admitted again. Blood culture was positive for streptococcus viridans. Moreover, echocardiogram revealed valvular vegetation on the anterior mitral leaflet, which is the characteristic finding of infective endocarditis. Antibiotics were so effective that his clinical course was relatively good with minor cerebral infarction during chemotherapy. Little is known about the prognosis and late complication of PTMC. However, our reported case may suggest that prophylactic chemotherapy might be recommended at least in some cases showing mitral regurgitation after PTMC. PMID- 1896670 TI - [Meniere's disease. A psychosomatic disease?]. AB - Although psychosomatic aspects of Meniere's disease have already been pointed out by some authors, few papers have been publisched on this question. 48 patients suffering from Meniere's disease underwent in addition of a complete audiological examination a psychosomatic study using two psychometric auto evaluation tests. It appears that patients suffering from Meniere's disease have a significantly different psychopathologic personality than normals (anxiety, depressive tendency, phobia). Besides, an obvious correlation is found between deafness, vertigo's recurrences and psychopathological disorders. These findings must be taken into consideration to treat patients suffering from Meniere'es disease. PMID- 1896669 TI - [Secondary Meniere's disease]. AB - Among 93 patients presenting the typical symptoms of a Meniere's disease associating an unilateral fluctuating hearing loss of sensorineural type, tinnitus and vertiginous attacks lasting minutes to hours, 40 patients (43%) presented in their personal history a particular otologic insult in the ear which later on developed into the full Meniere's symptomatology, or a particular systemic disease with otologic manifestations. The Meniere's triad appeared in these patients six months to twenty nine years after the initial otologic or systemic lesion. Among these initial lesions were 16 cases of sudden partial or complete deafness related to viral or bacterial infection, 3 cases of sudden cochleo-vestibular deficit and 1 case of vestibular neuritis, 5 cases of temporal bone fractures and 4 cases of significant acoustic trauma, 2 cases of otosclerosis, 1 case of chronicotitis media and 1 case of severe hearing loss after otologic surgery, 5 cases of meningo-encephalitis and 2 cases of acquired syphilis. These particular lesion could be, in our opinion, the releasing factor of the inner ear dysfonction leading eventually to a secondary Meniere's syndrome. PMID- 1896672 TI - [Immunological aspects of Meniere's disease]. AB - Among the various aetiopathogenetic hypotheses regarding Meniere's disease, the immunologic one has recently received a considerable amount of interest. Several studies have been performed using specific inner ear antigens (cell-mediated immunity) or by the evolution of circulating autoantibodies (i.e. against type II collagen or immune complex, etc...). We studied the immunological condition of 40 patients suffering from Meniere's disease, through the analysis of the following immunological blood tests: IgG, IgA, IgM, C3c, C4 and C-haemolytic complement level; circulating immune complexes, autoantibodies screening (Rheumatoid and antinuclear factors, mitochondrial smooth muscle and type II collagen antigens), cryoglobulins; T3, T4, T4/T8 monoclonal antibodies. Our results showed a rise in IgG levels in 6 patients (15%) and in IgA level, in 4 patients (10%). IgM blood level were abnormal in only one patient. Complement blood tests showed pathological results in 9 patients. All the patients had normal immunological tests regards to the autoantibody screening and T3, T4, T4/T8 monoclonal antibodies. The immunological results obtained in the patients suffering from Meniere's disease were compared with those of the control group (subjects suffering from vertigo by other causes than Meniere's disease); no significant difference was assessed between the two groups. The abnormal immunological pattern found in a few Meniere patients seems to be due to an aspecific response of the immune system, as the consequence of an alteration of the normal inner ear homeostasis. PMID- 1896671 TI - [Vestibular test in Meniere's disease]. AB - When it is well known that the electronystagmographic examination cannot diagnose the Meniere's disease, it is very useful to ensure that no other pathology is involved and for the follow up of the patients. The vestibulo-oculogram, on the other hand, suggests the presence of hydrops, according to the mechanical model. PMID- 1896673 TI - [Autoimmune Meniere's disease: current concept]. AB - The participation of an immunological mediation is unmistakable in certain cases of Meniere's disease. After exposition of the different experimental and clinical research, it is nevertheless still not possible to precisely determine the role of these immunological occurrences in the genesis of this disease. Clinical criteria should evoke this participation and lead to the detection of certain biological anomalies most frequently found by the different teams. PMID- 1896674 TI - [Value of immunobiological tests in Meniere's disease and in rapidly progressive sensorineural deafness]. AB - We have looked for abnormal immunobiologic test in 12 cases of Meniere's disease and 11 cases of rapidly progressive sensorineural hearing loss. After ruling out known etiologies, they were screened with non specific tests (sedimentation rate, electrophoresis, immunoglobulins, circulating immune complexes, cryoglobulins, complement system, auto antibodies) and inner ear specific tests (antibodies against human cochlea by indirect immunofluorescent test and lymphocyte transformation test against a pool of human inner ear. A non specific inflammatory syndrome was found in more than 50% of cases, specific tests of the inner ear were positive in 30% of cases. Corticosteroid therapy achieved a significant improvement of the hearing in 100% of the patients with a positive specific test, versus 50% of those with a negative result. A therapeutic protocol is suggested taking into account the results of the immunobiologic tests. PMID- 1896675 TI - [Pupillometry in Meniere's disease]. AB - The autonomic dysfunction is one of the etiopathogenetic hypothesis of Meniere's disease. We have already described the presence of an anomalous pupillary contraction, induced by methacholine, during the attack stage of Meniere's disease, without cardio-vascular reflexes involving. We have now employed, in a larger number of cases, a new digital equipment with infrared lighting system, built by us. The pupillary area was measured in darkness by a personal computer in basal condition (time 0) and 10, 20, 30, 45, 60 minutes after methacholine instillation. We have observed 16 cases of Meniere's disease (during attack stage and free stage), 23 cases of other vertiginous disorders (during attack stage and free strage), 10 normal subjects (5 cases of these also during a caloric test). The pupillary contraction was always highest at 30 minutes after methacholine administration. Normal subjects didn't show anisocoria and the contraction was weak and symmetric. Caloric test modified only a little the pupillary response. We observed the same results in other vertiginous disorders. During free stage of Meniere's disease there was little basal anisocoria but the contraction was normal and symmetric. During attack stage of Meniere's disease the contraction was much more evident and higher on the affected side. Meniere's disease crisis is characterized by cholinergic pupillary hyperreactivity, that is not caused by labyrinthic reflexes. We suppose this autonomic dysfunction of central origin. PMID- 1896676 TI - [Modeling of the semi-circular canal, application to labyrinthine hydrops]. AB - The angular accelerometer of vertebrates, the semi circular canal, is a pressure gage. The transformation, acceleration to pressure, is due to the inertia of the endolymph. In the 0 to 1 Hz frequency interval, the endolymph-cupula system can be described by a second order, localised parameter model with two real time constants. This mechanical model explains the occurr]nces of the vestibular ocular reflex during rotatory stimulations. However, some features of the response to caloric stimulations cannot be explained from this unique point of view. To correspond to these features, the SCC has to be considered as an inflatable structure, sensitive to weak pressure variations between the endolymph and perilymph. Different parameters of the mechanical model, the internal radius of the membranous canal, the dimension of the cupula and its elasticity coefficient depend on the inflating pressure. Meniere's disease is caracterised by hydrops, i.e. an increase of the pressure in the membranous SCC. The different mechanisms related to this hydrops, in particular introducing the inflating pressure as a second input to the ampular system, associated to a new concept of the mechanoneural transduction can explain the classical vestibular symptoms of Meniere's disease. Therefore, this overall mechanical model of the SCC indicates that hydrops is the mechanical cause of Meniere's disease and the primary cause is more likely to be a defect in the regulation loop of the inflating pressure. PMID- 1896677 TI - [Experimental model of endolymphatic hydrops]. AB - We have investigated by electrophysiology, morphology and pharmacology, the consequences of the surgical blocking of the endolymphatic duct in the guinea pig. We have demonstrated an immediate fluctuant CAP sensitivity loss on the low frequencies. Some weeks later a very high frequency loss can also be detected and finally after several months the mid frequencies are also affected and audiogram becomes relatively flat. This type of evolution of sensitivity loss corresponds remarkably well to the type of evolution of hearing loss observed in Meniere's patients. We have demonstrated that the early low frequency fluctuant losses are almost certainly a result of the selective atrophy of the short and middle stereocilia on the outer hair cells in the upper three cochlear turns, corresponding to a new hait cell pathology. Since ion channels are likely to be localised close to inter-stereocilia, row tip links this type of stereocilia atrophy could account for the low frequency fluctuant CAP sensitivity losses in hydropic cochleas. In addition this type of atrophy recalls a retrograde step in the ontogenesis of hair cells. Application of hydrostatic pressure directly to the endolymph via the endolymphatic duct provoked a high frequency sensitivity loss suggesting that endolymphatic pressure might be implicated in the late phase in the evolution of the hearing loss. Long-terme treatment by the diuretic chlorthalidone appeared to slow down the evolution of early low frequency CAP sensitivity loss and could reduce the volume of the hydrops. However in the long term the CAP sensitivity loss was not arrested.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1896678 TI - [Surgical treatment of Meniere's disease by sacculotomy, cochleo-sacculotomy and transtympanic aerators]. AB - Sixty-two patients suffering from severe Meniere's disease with invalidating vertigo attacks were treated between 1976 and 1987 by three minoir surgical procedures: sacculotomy (19), cochleo-sacculotomy (15) or a transtympanic ventilation tube (28). The results were assessed after the second post-operative year according to the criteria of the American Academy of Otolaryngology (1985). The overall success rate for vertigo control was 79% with sacculotomy, 80 with cochleo-sacculotomy and 82% with transtympanic ventilation tubes. Severe permanent hearing-losses occurred in 20% after sacculotomy and cochleo sacculotomy. Drop-attacks were not improved. These three surgical procedures give similar results with respect to vertigo control without any vital risk. The precise mechanisme of action in these procedures is not yet well understood. PMID- 1896679 TI - [Surgery of the endolymphatic sac and preservation of hearing in endolymphatic hydrops]. AB - Vertigo is the most important symptom of Meniere's disease both from the standpoint of follow-up and indication for surgery. But although vertigo is an alerting symptom for both the patient and the physician, we believe that the hearing level is the most reliable and even the single sign in determining the recent status of the disease. Between 1983-1989, 42 patients with various types of Meniere's disease (MD) (34 typical MD, 3 cochlear MD and 3 vestibular MD) underwent endolymphatic sac surgery at ENT department of Gazi University School of Medicine. In the typical MD group, patients with a duration of symptoms of less than one year prior to surgery revealed better postoperative results; 91% fell into class A and B, whereas this rate was found to be lower (40%) in patients with symptomatology lasting for more than one year. In conclusion, especially in bilateral cases, given the importance of the hearing, early sac surgery is thoroughly recommended for the conservation of hearing. PMID- 1896680 TI - [Balance in deaf children]. AB - The author notes the absence of vertigo in deaf children but, on the other hand, noted 7% instability in a group of 176 children. The electronystagmogram is modified rather often; 30 out of 68 cases of clear hypoexcitability or inexcitability. Dysrhythmia is frequent. Finally, the author emphasizes the relevance of associating posturography for exploring balance in deaf children. PMID- 1896681 TI - [Autoimmune deafness and myasthenia]. AB - The author reports a case of severe myasthenia in a 40 year-old women who presented an endocochlear type autoimmune deafness of progressive and bilatereal appearance during the evolution of her disease. It was associated with oropharyngeal and laryngeal disorders on top of which oculopalpebral anomalies were added. PMID- 1896683 TI - [Atypical complication of surgery for otospongiosis: the formation of cholesteatoma]. AB - Presenting a clinical case, the authors reveal the possible cholesteatoma complications arising from otospongious surgery. He notice that there are very few literature about similar cases. Underlining the rarity of this complication, the authors will put forward concisely the principal etiological mechanisms occurring in this kind of pathology. Since the reoperation must often be carried out on fragile inner ears, the authors stress on the necessity to respect the elementary rules of prevention in order to avoid the formation of precholesteatoma states. PMID- 1896682 TI - [Cochleovestibular syndrome disclosing dolicho-ectasis of the basilar trunk and vertebral artery]. AB - The authors present a case of a cochleovestibular syndrome with a scanner showing a calcified dolico-ektasis of the basilar truncus and the left vertebral artery. The patient had typical Meniere's disease symptomatology. A retrolabyrinthic diagnosis with substantial recruitment was indicated by the results of the audio vestibular explorations (stapedius reflex, electroculography, early brainstem evoked response, electrocochleography). The electrocochleography with glycerol test indicated labyrinthic hydrops. Finally, some reflections on the role of neurovascular problems in the pathogeny of some cochleovestibular syndromes are put forward. PMID- 1896684 TI - [Acute necrotizing sialometaplasia of the parotid gland]. AB - Parotidean localization of acute necrotizing sialometaplasia is exceptional. Based on one observation, the authors evoke the diagnostic and physiopathological problems raised by this localization. The association of facial paralysis and a parotidean tumor make the case presented interesting, leading to exploratory surgery which can alone provide a diagnosis. PMID- 1896685 TI - [Stapes decompression]. AB - Footplate decompression, which has been described in Lyon in 1965, can be easily performed under local anesthesia. The surgical procedure consists of a 8/10 mm diameter stapedotomy followed by an obturation with spongel, gelfoam or a piece of thin fascia. The operation is not a labyrinthectomy or a sacculotomy but aims to decompress endolymphatic hydrops in Meniere's disease. It must be realised only in case of typical unilateral Meniere's disease with disabling vertigo and very poor residual hearing. More than two hundred cases have been operated on. Vertigo has been relieved in 90% of the operated cases, tinnitus less severe in 50% of cases and hearing sometimes worse but often unchanged. In patients suffering from a unilateral Meniere's disease with disabling vertigo and poor residual hearing, footplate decompression appears to be one of the most simple safe and effective surgical procedures. PMID- 1896686 TI - [Experimental model of cochlear implant in newborn guinea pigs: different techniques of implantation]. AB - To answer the question whether a chronic electrical stimulation might be capable to induce a post-natal development of the auditory pathway, we performed a chronic prothetic implantation of the inner ear of 28 guinea pigs. Three stimulation systems have been utilized. An implantable solid state system, an external stimulator with head fixation and an external stimulator with fixation on the back of the animal. Because of the very small size of the new-born guinea pig, the most suitable system proved to be the external stimulator with fixation on the back. PMID- 1896687 TI - [Study by radiolabelling of the residual time of a therapeutic gel in the nasal fossae]. AB - The residence times in the nose of the liquid and gel forms of the same therapeutic preparation were compared in 7 healthy subjects. A 50 microliters drop of the preparation, labelled with Tc99m, was placed down the head of the inferior turbinate, and the kinetics of its clearance from the site of deposition was monotired using a gamma camera, during 60 minutes for the liquid and 120 minutes for the gel. The average times for removal of 50% of the labelled material from the site of deposition were 10.3 minutes and 28.6 minutes for the liquid and gel forms respectively. The slower removal of the gel form is probably due to a mechanical effect, and seems to affect the whole nasal passage. The contact time between the preparation and the mucosa is increased in this galenic form and this should improve the efficiency of the preparation. PMID- 1896688 TI - [Sudden deafness: different pathologies and results of treatment by normovolemic hemodilution]. AB - The authors report 75 cases (including 4 children) treated between 1983 and 1988 by normovolemic hemodilution, corticoids and vasodilators for deafness of various origins. This treatment has an action in deafness of brutal occurrence and all the more so when applied early. The youngest subjects, with viral disorders and the oldest with vascular disorders receive less favourable prognoses. The main risk factors found are represented by a previous vascular and otological history. When hemodilution fails, it is best to associate hyperbaric oxygen therapy rapidly. PMID- 1896689 TI - [Hennebert's sign in Meniere's disease]. AB - The fistula sign without middle-ear lesion, also known as the Hennebert's sign, was observed in 7 (14%) subjects among 50 patients with unilateral Meniere's disease. The Hennebert's sign was obtained in 4 cases (57%) by negative pressure in the external auditory canal, by positive pressure in 2 cases and by both positive and negative pressures in 1 case. The Hennebert's sign is characterized by a few beats of horizontal nystagmus seen under Frenzel glasses. Caracteristically this nystagmus is of low frequency and amplitude. Most patients indicate simultaneous sensation of dizziness. The presence of Hennebert's sign seems to indicate in most cases the existence of an endolymphatic hydrops with contact of the saccular wall up to the internal face of the footplate (internal sacculostapedopexy). The test was also performed on the controlateral healthy ear used as a control. No Hennebert's sign was obtained on the healthy side. None of the patients showed any complication following the provocation of Hennebert's sign. PMID- 1896690 TI - [Local approaches to extensions of laryngeal cancers: implications for anatomo pathological testing of surgically removed specimens after laryngectomy]. AB - The pathological examination of partial or total laryngectomy specimens for primary laryngeal cancer presents some difficulties that are related to the complex anatomical configuration of this organ. Moreover, the local spread is depending on the primary location of the lesion. The pathological findings are of special importance because they are used for planning postoperative treatment and for predicting prognosis. The gross study is the most important time but it needs to be completed by histopathological study on whole organ serial sections or on selected parts. This last event is often the only appropriate one for routine examination but it needs to know as well as possible the usual modes of invasion in accordance to the primary location. This work presents the results of the pathological topographic study in 251 partial or total laryngectomy specimens that were removed because of primary laryngeal cancer. PMID- 1896691 TI - [External injuries of the larynx. Our experience apropos of 55 cases]. AB - Reporting 55 cases of laryngeal trauma, the authors detail the etiologies and the lesions observed and expose their trauma management. Endoscopic results are basic in the evaluation of the gravity of the trauma. Radiological investigations, especially C.T. scan, take the second place. The use of endolaryngeal stent in the surgical treatment is as limited as possible. A precise lesional staging and a great rigour in the operative management can only guarantee the recovery of normal vocal and respiratory functions. PMID- 1896692 TI - [Electromyography of the larynx in the diagnosis of spontaneous or post thyroidectomy laryngeal paralysis]. AB - Electromyographic assessment (EMG) of the larynx is very important for diagnostic and prognostic in cases of unmoving larynx: definition that authors like better than larynx palsie or recurrent nerve palsie because it is impossible to know why the larynx do not move in many cases (15f for 20 cases in the experience of the authors). EMG must be realized on several muscles and not only on the vocal fold muscle. It is necessary to realize several EMG to have a good follow up. If we have the proof that it is a case of definitive recurrent palsie the authors think that it is now, indication of nervous selective anastomosis by micro-surgery. PMID- 1896694 TI - [2 cases of rhinogenic intracranial complications with normal rhinoscopy]. AB - Two cases of non-postoperative rhinogenic intracranial complications are reported: patient 1 was a 25-year-old female with meningitis and right orbital phlegmon, and patient 2 was a 21-year-old male with a brain abscess. Main symptoms in these patients were meningeal signs and high fever, and intranasal findings were normal in both patients. The diagnosis was not made until computed tomography revealed paranasal abnormalities. Soon after surgical intervention and treatment with large doses of antibiotics. These patients were completely cured of intracranial complications. It should be beared in mind that rhinogenic intracranial complications with lack of intranasal abnormal findings, as in these patients, can exist even today. PMID- 1896693 TI - [Apropos of a large parapharyngeal tumor. Imaging and surgery]. AB - Based on the observation of a voluminous neurinoma of the carotid groove and of the posterior subparotid space, the authors highlight the wide range of parapharyngeal tumors and develop the anatomical bases which shed light on the clinical picture and guide the surgeon. The surgical indication must be put forth cautiously, taking into account the evolutive character of the tumor, the dangers it implies particular in Recklinghausen's disease. Modern radiology plays a major role in the diagnosis and treatment by perfectly visualizing the tumor, its vascularization and its relations with the walls and contents of the parapharyngeal spaces. It will supply indispensable information for directing the coordination between the ENT specialist, the vascular surgeon and the neurosurgeon. PMID- 1896695 TI - [A curiosity in ORL pathology: myiasis of the otorhinolaryngologic cavities]. AB - The authors report a case of auricular myiasis with a review of literature. Diagnostic, therapeutic and prophylactic means established facing this parasitical disease are analysed. PMID- 1896696 TI - [2 cases of neurinoma of the mastoidal portion of the facial nerve: diagnostic contribution of MRI]. AB - The authors report 2 cases of patients presenting a neurinoma of the 3rd portion of the facial nerve. In the 2 cases, the surgical observations correlated perfectly with the results of the radiological examinations (scanner and MRI). The clinical and paraclinical presentation of this rare tumor is recalled, emphasizing the additional contribution of imaging techniques: the scanner is indeed indispensable for evaluating the osseous destructions on the intrapetrous trajectory of the facial nerve, whereas MRI (in particular with injections of gadolinium) evaluates the exact tumoral limits as best as possible. PMID- 1896697 TI - [Exostosis of the external auditory canal: clinical and therapeutic aspects]. AB - Based on the study of 25 cases, the authors recall the frequency and pathogeny of these lesions, specifying the surgical technique and presenting their results. The risks of this surgery lie in the ever possible impairment of the facial nerve and labyrinthization on treble frequencies (2 cases). The incidents are tympanic perforation (1 case) and the opening of the temporomandibular joint. It is not always possible to preserve the skin of the external auditory canal. It can be reconstructed by a free (3 cases) or pedicle (3 cases) graft of more simply in case of small loss of substance by a temporal fascia graft. PMID- 1896698 TI - [Diagnostic contribution of the new imaging systems in arterial and nerve disorders of the posterior fossa]. AB - Giant aneurysms of the vertebrobasilar system are rare, representing only 5% of intracranial aneurysms and are the cause of severe pseudo-tumoral of hemorrhagic syndromes. Their endovascular or surgical treatment is always very dangerous. The basilar megadolicho-artery, of congenital origin, is frequently expressed by a hemispasm or facial neuralgias. The diagnosis is made easily by TDM and angiography. Abstaining from therapy is the rule. The much debated vascular rings are often held responsible for the microvascular compression syndrome, leading to facial neuralgias, hemispasm, Menierie-form or pseudo-tumoral cochleo-vestibular syndrome, neuralgia of the IXth or spasmodic torticollis. The radiological diagnosis is very difficult and mainly depends on MRI. However, quite often, only surgical exploration enables the diagnosis and treatment of the neurovascular compressive syndrome. PMID- 1896700 TI - [Otoplasty: results of a modified form of Mustarde's method]. AB - In order to investigate the results obtained after surgical treatment of prominent ears with a modified method basically derived from the technique of Mustarde 340 patients had been interrogated and 150 had been examined postoperatively. In 91.4% of the cases the patients themselves and in 84.7% the surgeon was satisfied by the postoperative result. Recurrence was observed in 17% and was due partly to the intermittent use of a resorbable suture material. In some cases recurrence consisted in a slight asymmetry, that was not really disturbing and did not need a further correction. A fundamental advantage of our surgical method is the fact that the cartilage has not to be destroyed, so that ugly and unnatural rims are avoided as well as some further postoperative complications (othematoma, perichondritis, pain and sensibility to the cold). Revision surgery even by another technique is always possible because the cartilage is left intact. PMID- 1896699 TI - [An atypical case of Wegener's disease]. AB - The authors report on a case of Wegener's syndrome diagnosed fortuitously by the discovery of a perforation of the nasal septum during a bronchial fibroscopy for monitoring of a pulmonary fibrosis. In addition to the late appearance of the nasal perforation, the clinical picture includes classic polyvisceral impairment with pulmonary fibrosis, polyarthralgias and renal insufficiency. After 21 months of treatment, a stabilization of the visceral lesions was recorded, with the all but total disappearance of the E.N.T. lesions. PMID- 1896701 TI - [Causes of failures of rhinoplasty and therapeutic attitudes]. AB - 10 to 15% of all rhinoplasties need a second operation. This depends mostly on an inexact analysis, an insufficient planing or an inadequate rough technique. Typical examples of cases of secondary rhinoplasties are demonstrated. PMID- 1896702 TI - [Calcium alginate as a nasal pack]. AB - Alginates are highly absorbent, gel-forming materials with haemostatic properties. The aim of this study was to compare calcium alginate to Telfa as a postoperative nasal pack in a prospective randomised clinical trial. Eighty two patients entered the trial. There were 55 males and 27 females whose ages ranged from 13 to 74 years (mean 34.7 years). Immediate postoperative bleeding was controlled in all cases irrespective of the pack used. There was no difference in the incidence of postoperative complications between the two groups. Calcium alginate is a safe and effective alternative to Telfa as a postoperative nasal pack. PMID- 1896703 TI - [Current techniques of pharyngo-velar reconstruction after excision for cancer]. AB - Carcinological surgery of the pharyngo-velar region poses delicate problems of reconstruction in exereses exceeding the midline. To avoid false alimentary pathways through the nose and phonatory problems (open rhinolalia), we propose the use, with or without the combination of a muscular cutaneous flap, of a free antecubital flap or of a latter is apparently fully satisfactory on the functional plane with the additional advantage of not leaving any aesthetic sequellae. PMID- 1896704 TI - [Bulbar auditory nuclei: morphological study, consequences for implantation of electrodes]. AB - Many bilaterally profoundly deaf individuals cannot benefit from a cochlear implant because the eight nerve is not intact from the cochlea to the brain stem. For these individuals, electrical stimulation of the cochlear nuclear complex (CNC) may partially restore the sensation of hearing. Histological studies were done on 12 brain stems containing the region of the CNC and findings of this study seems important to accurate implantation of the prosthesis on the CNC for chronic electrical stimulation. Apparently the spheroid cells of the inferior ventral cochlear nucleus (IVCN) represents the site of the CNC for such stimulation. PMID- 1896705 TI - [Autonomic innervation of the vessels of the nasal mucosa: current concepts]. AB - The nasal cycle enables the conditioning of air breathed in. It depends on the vascular vegetative innervation. Whilst its central diencephalic origin is probable, its mechanics remain mysterious. The involvement at the loco-regional level of short circuits ensuring the anatomical links between the vegetative, sensitive and cellular systems of the nasal mucosa is the basis of a new approach to chronic rhinological pathologies and certain facial algias. PMID- 1896706 TI - [A developmental anomaly of Meckel's cartilage]. AB - An atypical evolution of the mandibular cartilage was recorded in systematic dissections of the neck in the Anatomy Laboratory. This anomaly led to the formation of a supernumerary bony fragment in the concavity of the lower edge of the mandibular arch, with a slight adhesion thereto. This observation is reported by the authors after a recapitulation of the embryology. PMID- 1896707 TI - [Idiopathic systemic fibrosis]. PMID- 1896708 TI - [Treatment of diffuse interstitial pulmonary fibrosis]. AB - At the stage of established pulmonary fibrosis there is no effective treatment. Hence the necessity of an early diagnosis at the "cellular" stage of diffuse interstitial fibrosing pneumopathy, which offers the best chances of improvement under corticosteroid therapy. Current biopathological researches on the dynamic mechanisms of fibrosis (fibrogenesis, fibrolysis) should open therapeutic lines involving cytokines and/or their receptors, including at the stage of gene transcription. PMID- 1896709 TI - [Emergency hospitalization of the elderly and geriatric internal medicine]. PMID- 1896710 TI - [Cutaneous plasmacytoma: review of the literature apropos of a case]. AB - Extramedullary plasmocytomas are ubiquitous plasmocytic tumours which are principally located in bones and mucosae but rarely found on the skin. Clinically, they present as purplish-blue cutaneous nodules or, less frequently, as papular or urticarial eruptions. The diagnosis rests on histology and immunostaining. Cutaneous plasmocytomas are usually divided into two types: (1) primary plamocytomas which occur in the absence of myeloma, present as solitary or multiple skin tumours, accompanied or not by monoclonal gammopathy, and have an imperfectly known course and prognosis; (2) secondary plasmocytomas--a case of which is reported here--which appear in the course of a large tumoral mass myeloma and have a very poor prognosis. PMID- 1896711 TI - [The mysteries of lipoprotein (a): a bridge between thrombosis and atheroma]. AB - Nearly 30 years have elapsed since Berg discovered a genetic variant of low density lipoproteins (LDL) which he called lipoprotein (a), abbreviated Lp (a). Lp (a) rapidly appeared as an independent factor of atherosclerosis. Its physico chemical characteristics are well-known, but this cannot be said of its function, its metabolism and the exact mechanism of its contribution to atherogenesis. The plasma Lp (a) concentration is determined genetically and its seems that few factors can lower it. Owing to its structural analogy with plasminogen, Lp (a) has been suspected to bind fibrin by a competitive mechanism, thereby facilitating thrombosis, a necessary step in the progression of atherosclerosis. However, these results remain controverted, and indeed there is some evidence of a possible interaction between Lp (a) and alpha-2-antiplasmin, a physiological inhibitor of fibrinolysis, an effect that would accentuate fibrinolysis. This paradoxical action of Lp (a) and the various mysteries which still shroud this lipoprotein are perhaps due to the diversity of its isotypes. PMID- 1896712 TI - [Muscular glycogenoses]. AB - Muscular glycogenosis is a disease resulting from genetic abnormalities altering an enzyme which is involved in glycogen metabolism. In addition to disorders of glycogenolysis and glycolysis, there are other pathological processes such as acid maltase (alpha-glucosidase) deficiency and diseases associated with abnormal glycogen structure. Glycolysis is the only metabolic pathway that can produce ATP in the absence of oxygen. It is then easy to understand that any disturbance in this energy pathway can result in dysfunction of the muscle machine and in a number of symptoms which are common to these abnormalities. An overall review of the various diseases know to exist on the glycogenolytic and glycolytic pathway will enable the reader to acquire a better knowledge of their particular features. PMID- 1896713 TI - [Hypothyroid hypertrophic myopathy following mantle irradiation for Hodgkin's disease. A case]. AB - The authors report a case of hypothyroid hypertrophic myopathy consecutive to mantle irradiation for Hodgkin's disease. A rise in TSH level is frequent after mantle irradiation and it justifies prolonged monitoring of these patients' thyroid function, in view of the risk of patent hypothyroidism and perhaps cancer. The patient's age, the pre-irradiation lymphography and the chemotherapy associated with radiotherapy are all factors that influence the incidence of thyroid dysfunction, but there is no agreement concerning their relative importance. Hypertrophic myopathies due to hypothyroidism are rare, and their dramatic clinical presentation contrasts with an almost normal muscle histology. Alterations of energy metabolism and changes in the properties of myosin induced by hormonal deficiency account for the muscular weakness of these patients. On the other hand, the mechanism of muscle hypertrophy remains controverted, the most probable theory being and increase in the number of myotubes. Following irradiation, notably for Hodgkin's disease, the frequency of hypothyroidism requires a regular and systematic laboratory follow-up. Replacement therapy must be instituted if the basal TSH level increases, even if the T4 level is normal. PMID- 1896714 TI - [Primary carcinoma of the pituitary gland with Cushing's syndrome and metastases. Apropos of a case with review of the literature]. AB - We report the case of a 25 year old man with pituitary carcinoma with Cushing's syndrome. Though the diagnosis was initially proposed, it was only confirmed by the appearance of meningeal and lymphatic metastases. These were secretory, as confirmed by immunocytochemistry and electron microscopy. These tumours are rare, whether they secrete or not, and can be confirmed only by the existence of metastases, most often in the brain or the liver. PMID- 1896716 TI - [Mitochondrial cytopathies]. AB - Mitochondrial cytopathies are diseases due to a defect of mitochondrial respiratory chain and are characterized by the presence of morphological abnormalities of mitochondria (ragged red fibers). The clinical manifestations can be polymorphic as various organs may be involved; but in general, these disorders affect either muscle alone (progressive external ophtalmoplegia, myopathy with weakness) or muscle and brain (encephalomyopathies). Some of these diseases may be due to alterations of the mitochondrial genome. Diagnosis can be achieved through the following steps: measurement of lactate, pyruvate and ketone bodies after fasting followed by a carbohydrate rich meal and/or exercise; histological examination and biochemical investigation of a skeletal muscle biopsy; study of possible mitochondrial genome alterations. PMID- 1896715 TI - [Late recurrence of Miller-Fischer syndrome. Physiopathogenic reflections about a case]. AB - The physiopathology of the syndrome of ophtalmoplegia-ataxia-areflexia hyperproteinorachia, firstly described by FISHER in 1956, remains a matter of controversy among neurologists. We report a new case of recurrence of a MILLER FISHER's syndrome. The involvement of peripheral and central structures is discussed according to recent knowledges about the immunopathology of inflammatory polyneuropathies. PMID- 1896717 TI - [Epidemiology and treatment of gastroduodenal lesions caused by non-steroidal anti-inflammatory agents]. AB - The most common serious adverse reactions to nonsteroidal anti-inflammatory drugs (NSAIDs) are those affecting the gastro-intestinal tract. There is epidemiologic evidence that NSAIDs use is associated with the development of gastric ulcer and with upper gastrointestinal bleeding and perforation of both duodenal and gastric ulcers. The individual risk is low but given the widespread use of NSAIDs, the number of cases is large with appreciable morbidity and mortality. The main risk factors are age above 65, previous ulcer history and treatment with several NSAIDs. Prophylactic therapy is justified in high risk patients. Synthetic prostaglandin misoprostol has been shown to reduce significantly the frequency of gastric ulcer in patients on NSAIDs. By contrast, H2 receptor blockade with ranitidine has been demonstrated to prevent duodenal but not gastric ulcers. Gastric and duodenal ulcers associated with NSAIDs appear to heal on H2 receptors antagonists and prostaglandins even if NSAIDs are continued. However, large gastric ulcer may heal slowly over 8 to 12 weeks. The place of omeprazole remains to be determined. PMID- 1896718 TI - [Spastic paraplegia caused by bilateral cerebral metastases of rectal carcinoma]. PMID- 1896720 TI - [Association of Sweet syndrome and salmonellosis]. PMID- 1896719 TI - [Rhabdomyolysis with acute renal insufficiency: role of the association of fibrate and hypothyroidism]. PMID- 1896722 TI - Obstructive sleep apnea treatment: peripheral and central effects on plasma renin activity and aldosterone. AB - To assess the effect of obstructive sleep apnea treatment on plasma renin activity (PRA) and plasma aldosterone seven male patients were studied under two conditions: untreated and treated with nasal continuous positive airways pressure (CPAP). PRA and plasma aldosterone were measured at 10-min intervals for both nights. CPAP treatment diminished the urinary and Na+ excretion, whereas plasma volume increased. The mean levels of PRA and aldosterone were significantly enhanced by the treatment, increasing respectively from 1.5 +/- 0.3 to 3.0 +/- 0.7 ngAI ml-1.hr-1 (p less than 0.05) and from 8.0 +/- 1.0 to 12.0 +/- 1.7 ng.100 ml-1 (p less than 0.05). PRA curves reflected the overall sleep structure as similarly described in normal subjects. The apnea-induced sleep disturbance led to flat PRA profiles and the restoration of a normal sleep pattern by treatment restored the PRA oscillations related to the sleep cycles and consequently restored aldosterone oscillations. The mean amplitude of these oscillations increased respectively from 1.0 +/- 0.1 to 1.8 +/- 0.4 ngAI ml-1.hr-1 and from 5.4 +/- 1.2 to 10.9 +/- 1.9 ng.100 ml-1. These results suggest that CPAP treatment modifies the nocturnal patterns of PRA and aldosterone by increasing their mean levels and their oscillation amplitude. This indicates increased secretion, which contributes to the normalization of urine and Na output. PMID- 1896721 TI - Sleep deprivation in the rat: XIII. The effect of hypothyroidism on sleep deprivation symptoms. AB - Previous studies of rats subjected to total sleep deprivation by the disk-over water method had shown a large increase in energy expenditure (EE) and an initial increase followed by a later decrease in body temperature (Tb). It had been proposed that the increase in Tb resulted from regulation toward a higher temperature or setpoint, that the later decline in Tb resulted from excessive heat loss, and that the increase in EE supported both of these thermoregulatory changes. To evaluate this proposed role of the increase in EE, we examined whether blunting the EE rise in sleep-deprived rats by making them hypothyroid attenuated and/or shortened the initial increase in Tb and accelerated the later decline in Tb. Rats made hypothyroid by propylthiouracil administration (TxD rats) were totally sleep deprived and compared to hypothyroid yoked control (TxC) rats and to previously studied, untreated, totally sleep-deprived (TSD) rats. Neither TxD nor TxC rats showed large increases in EE like those of TSD rats. TxD rats did not initially increase Tb, as TSD rats had. Presumably, TSD rats had been able to support an initially elevated Tb, in spite of excessive heat loss, by large increases in EE, although even these increases were eventually insufficient. TxD rats showed much earlier and greater declines in Tb than TxC and TSD rats, eventually becoming severely hypothermic. These results support the interpretation that the large increase in EE previously seen in TSD rats had been compensatory for deprivation-induced thermoregulatory deficits. TxD rats survived an average of 17.1 days, which was not significantly different from survival time in TSD rats. However, there were differences in mortal processes between the two groups. TxD rats died or were sacrificed after chronic, severe hypothermia without observable signs of other morbid pathology. TSD rats had not shown similarly low Tb until just prior to death, but had shown signs of severe pathology, including severely debilitated appearance, disheveled fur, and severe lesions on their tails and on the plantar surfaces of their paws. These signs were diminished or absent in TxD rats, possibly due to blunted EE, lower Tb, or other effects of hypothyroidism. Because the skin changes seen in TSD rats were minimal in TxD rats, they could not have been responsible for the excessive heat loss. PMID- 1896723 TI - Manifest sleepiness and the spectral content of the EEG during shift work. AB - Twenty-five three-shift workers in a process industry were subjected to ambulatory polysomnography during one afternoon and one night shift. The electroencephalographic (EEG) recordings were analyzed with spectral analysis. Subjective sleepiness increased during the night work but did not reach an extreme level. Five subjects fell asleep during night work and the involuntary naps were preceded by a few minutes of increased alpha (8-11.9 Hz) power density. Alpha and theta activity occurred in very short bursts. The hourly mean EEG alpha power density increased significantly but moderately during the night shift and correlated with subjective ratings of sleepiness. Theta power density (4-7.9 Hz) did not increase during the night shift, nor did it correlate with subjective sleepiness. It was suggested that the shift workers could prevent much of the polysomnographic manifestations of sleepiness by various types of activity (including succumbing to sleep). It was also suggested that averaging power density values across long time periods might not be an optimal strategy for detection of sleepiness, but rather some method of emphasizing the occurrence of alpha or theta bursts. PMID- 1896724 TI - Green light attenuates melatonin output and sleepiness during sleep deprivation. AB - Melatonin output covaries with sleepiness, with both peaking early morning. Bright white light suppresses this output, but it is not known if such treatment ameliorates nighttime sleepiness during sleep deprivation. However, sleep deprived subjects find such light irritating. Humans are particularly sensitive to green light, and melatonin output is more readily suppressed by this hue. A pilot study using different green light regimens showed that sleep-deprived subjects well tolerated 2,000 lux green light given 10 min hourly, and that this dose reduced nighttime melatonin output. The main study gave this light treatment vs. a low intensity red/green light control, from 1900 hr for 11 hr, to two groups of subjects (n = 6 each) sleep deprived for 36 hr. Urine was collected at 6-hr intervals during sleep loss and on a baseline day. Vigilance performance, subjective sleepiness, and oral temperature were monitored during sleep loss. The experimental condition suppressed urine 6-hydroxymelatonin sulfate (aMT6s) output between 0000 hr and 0600 hr, and increased it 0600-1200 hr; but there was no change in total 24-hr values. The control condition had no such effects. The oral temperature rhythm remained unchanged. Vigilance and subjective sleepiness were improved significantly relative to control values during 0000-0600 hr; these improvements were maintained somewhat over the 0600-1200-hr period, contrary to what one might expect if the delayed melatonin surge at this time was increasing sleepiness. Although the bright green light helped counteract sleepiness, any causal link with changes in melatonin output seem tenuous. PMID- 1896725 TI - Modification of sleep respiratory patterns by auditory stimulation: indications of a technique for preventing sudden infant death syndrome? AB - Sudden infant death syndrome (SIDS) has been associated with premorbid respiratory irregularities that may contribute to the subsequent occurrence of SIDS (e.g. by chronic hypoxia). Conventional apnea alarms will detect periods of extended apnea but not other chronic respiratory irregularities that could contribute to SIDS. The effect of a brief, quiet, repetitive auditory stimulus on the sleep respiratory behavior of infant dogs and pigs was assessed. Stimulus presentation was associated with an increase in the sleep respiration rate irrespective of the stimulus presentation rate being faster or slower than the baseline respiratory rate, and irrespective of the pattern of presentation being regular or random. These results suggest that apnea monitoring systems may be improved by an additional function in which less extreme respiratory irregularities initiate the time-limited presentation of a quiet, repetitive, auditory stimulus, aimed at normalizing the respiratory pattern. This function could enhance the preventative role of the alarm systems by reducing the development of pathology that may promote some instances of SIDS. PMID- 1896726 TI - Inter-rater reliability for scoring periodic leg movements in sleep. AB - This study investigated inter-rater reliability for scoring periodic leg movements in sleep (PLMS) and related phenomena. Five highly experienced polysomnographic technologists each scored 24 nocturnal polysomnograms, the majority of which contained an appreciable number of PLMS. Results indicated high inter-rater reliability for some variables but more modest reliability for others. We discuss these findings in terms of efforts of standardization in polysomnographic scoring of sleep disorders. PMID- 1896727 TI - Night-to-night variability of disturbed breathing during sleep in an elderly community sample. AB - Night-to-night variability of breathing and oxygenation during sleep was examined with portable monitoring equipment in 30 residents of a retirement village. Subjects had a variety of health problems as might be expected in the elderly, but all were living independently in self-contained units. None had clinical features to suggest obstructive sleep apnea. Two pairs of consecutive nights were studied, separated by 4-6 months. Satisfactory recordings on all four nights were obtained in 15 subjects, and in these subjects variability of measurements was examined across nights 1-4 using the kappa (K) statistic. There was low but significant agreement in estimated total sleep time (K = 0.23, p less than 0.01) and estimated wakefulness after sleep onset (K = 0.18, p less than 0.05) as assessed with a wrist actigraph. Good agreement was found among measures of disturbed breathing during sleep whether expressed in terms of numbers of events [respiratory disturbance index (RDI), K = 0.62, p less than 0.0001], their duration (event minutes, K = 0.53, p less than 0.0001), or associated disturbance of oxygenation (% cumulative time less than 90% SaO2, K = 0.50, p less than 0.001, n = 9). Twenty-eight subjects had at least two nights' satisfactory recordings. Although some of these individuals showed considerable variation in RDI, this had little overall effect on classification of them into normal (RDI less than or equal to 15) and abnormal groups. The accuracy of the first night's recording in predicting classification derived from recording on three or four nights was 83%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1896728 TI - The exploding head syndrome: polysomnographic recordings and therapeutic suggestions. AB - Attention has recently been drawn to a condition termed the exploding head syndrome, which is characterized by unpleasant, even terrifying sensations of flashing lights and/or sounds during reported sleep. Nine patients complaining of sensations of explosions in the head during sleep or drowsiness were investigated with polysomnographic recordings. None of them had any neurological disorder. Five patients reported explosions during the recording sessions. According to the recordings, the attacks always took place when the patients were awake and relaxed. In two cases abrupt electroencephalographic (EEG) and electromyographic changes indicating increasing alertness were recorded at the time of the reported attacks. In the remaining three cases no EEG changes were seen. Thus, there were no indications of an epileptic etiology to the condition. In all patients the symptoms ameliorated spontaneously with time. The severity of the symptoms was reduced by reassurance of the harmlessness of the condition. Clomipramine was prescribed to three patients who all reported immediate relief of symptoms. It is concluded that symptoms of this type are probably not true hypnagogic phenomena but may be an expression of emotional stress in the awake state. PMID- 1896730 TI - Genetic markers in familial narcolepsy. AB - We studied three patients in a single family (father and two sons), all with long histories of overwhelming daytime sleepiness, hypnagogic hallucinations and sleep paralysis. Two of the three had a clear history of cataplexy. Multiple sleep latency tests revealed extremely short sleep onset latencies and at least two sleep onset rapid eye movement periods in each patient. Histocompatibility studies were remarkable for negative HLA-DR2 antigens in all three. PMID- 1896729 TI - Juvenile onset narcolepsy in an individual with Turner syndrome. A case report. AB - We describe an 8 year old girl who presented with excessive daytime sleepiness and frequent falling. Following extensive investigations, the diagnosis of both narcolepsy and Turner Syndrome were confirmed. To our knowledge, this is the first report of these two conditions in the same individual. Both conditions are common, but the early expression of narcolepsy is unusual. Although there is a genetic basis for each, the two conditions are not necessarily related since Turner is an X-linked abnormality, while narcolepsy has an autosomal basis. Nonetheless we wonder if the hormonal balance of Turner Syndrome might have some role to play in the early expression of narcolepsy. PMID- 1896732 TI - Bibliography of recent literature in sleep research. PMID- 1896731 TI - ADAM nasal CPAP circuit adaptation: a case report. AB - ADAM (Airway Delivery And Management) circuitry for nasal continuous positive airway pressure (CPAP) (administration/delivery) was not successful in the delivery of nasal CPAP to a patient. Adaptations to the circuitry were necessary to obtain a more comfortable fit. PMID- 1896733 TI - [Living the alcoholic life]. PMID- 1896734 TI - [Caring for the dignity of man]. PMID- 1896735 TI - [Childhood asthma]. PMID- 1896736 TI - [Technical note No. 102. Intermittent administration of subcutaneous morphine]. PMID- 1896738 TI - [The initial examination of the injured hand]. PMID- 1896737 TI - [The injured hand and its rehabilitation. The nursing role in the emergency department]. PMID- 1896739 TI - [The injured hand and its rehabilitation. In the operating room]. PMID- 1896740 TI - [The injured hand and its rehabilitation. The nursing role during hospitalization]. PMID- 1896742 TI - [Immunological safety in transfusions]. PMID- 1896741 TI - [The nursing role in rehabilitation of the hand]. PMID- 1896743 TI - [Capillary microscopy of the nails]. PMID- 1896744 TI - [The confused elderly person]. PMID- 1896745 TI - [AIDS: 10 years after]. PMID- 1896746 TI - [Portrait. "I want to understand". Interview by Odile Burrus]. PMID- 1896747 TI - [Dominique Frering. "How far is too far?". Interview by Christian Moreau]. PMID- 1896748 TI - [Care of the patient with multiple handicaps]. PMID- 1896749 TI - [Elaboration of a pain measurement scale]. PMID- 1896750 TI - [Concerning palliative care]. PMID- 1896751 TI - [Operative hysteroscopy]. PMID- 1896752 TI - [Evaluation of thyroid function]. PMID- 1896753 TI - [Evaluation of urinary sphincter function]. PMID- 1896754 TI - [For a nursing service department]. PMID- 1896755 TI - The language of epidemiology (II) PMID- 1896756 TI - Chronic fatigue syndrome. PMID- 1896757 TI - Relative survival of the gauche, the sinister and the adroit. PMID- 1896758 TI - The Brown University Program in Medicine. Class of 1991. PMID- 1896759 TI - Introducing medical students to patients: students' perspective. PMID- 1896760 TI - Yellow fever: the 1978 outbreak in Trinidad and Tobago. PMID- 1896761 TI - Benjamin Waterhouse and the kine-pox inoculations. PMID- 1896762 TI - The introducer of Jenner's new vaccination into America. PMID- 1896763 TI - The face of AIDS in Rhode Island. PMID- 1896764 TI - Detection of Wuchereria bancrofti specific antigens in the serum of endemic residents. AB - A sandwich enzyme-linked immunosorbent assay (s-ELISA) is developed for detecting circulatory antigens in individuals infected with Wuchereria bancrofti in an endemic area using antibody (Ig) against excretory-secretory-metabolic antigens of the microfilariae raised in rabbit (anti-mf-ESM) and labelled with alkaline phosphatase (ESM-Ig-conjugate). An optical density reading of a sample greater than 0.075 (after subtracting the background) was taken as positive in the s ELISA. When homologous (WbmfESM) and heterologous (sonicated antigens of human and model intestinal helminths-Ascaris lumbricoides. Trichuris muris, Necator americanus and Strongyloides ratti) antigens were spiked at 2.5, 5, and 7.5 microgram/well, rabbit ESM-Ig-conjugate reacted specifically with the samples containing homologous antigens. Amongst 21 sera in five different categories of non-endemic group, only four (two in helminth-ve and two in mixed intestinal helminthic group) were found to be positive. Out of 19 sera from endemic residents, three of 7 endemic normals (ENS), all microfilaraemics (mf+) (n = 7) and 4 out of 5 elephantoid patient sera were positive. This preliminary data show that rabbit mfESM-Ig-conjugate is efficient in detecting sera samples containing antigenic components of microfilariae. This assay was found to be discriminatory in detecting individuals carrying current infection. This test requires further validation with larger number of samples and it may prove of value for detecting lymphatic filarial infection. PMID- 1896765 TI - A seroepidemiologic survey of human dirofilariosis in Western Spain. AB - The objective of this work is to define the prevalence of IgM and IgG antibodies against Dirofilaria immitis in an exposed human population. 395 individuals attending primary care facilities in an area endemic with canine dirofilariasis were studied, as well as 100 non exposed individuals. An ELISA method was used for the detection of IgG and IgM antidirofilarial antibodies. Sera were preadsorbed with antigens of Toxocara canis, Ascaris suum, Echinoccocus granulosus and Fasciola hepatica to prevent cross reactions. Global seroprevalence was 9.3%. IgG antibodies were observed in the oldest sector of the population, while IgM antibodies were found only in its youngest half. No sex differences were observed. This result show that dirofilariasis is common in humans from endemic areas. Repeated contacts with the parasite are common and begin at a young age. PMID- 1896767 TI - Detection of Taenia solium antigens in merthiolate-form preserved stool samples. AB - Cysticercosis can be controlled by mass treatment of Taenia solium carriers in hyperendemic areas. An automated screening method suitable for mass application is required to determine the prevalence of taeniasis and the efficacy of its treatment, since existing methods of carrier detection are considered insufficient for this purpose. Thus, a biotin/avidin-enhanced enzyme-linked immunosorbent assay (ELISA) was designed, which detected T. solium antigens in supernatants of merthiolate-formalin preserved stool samples. The assay distinguished the nine T. solium carriers tested from 41 negative controls, but cross-reactivity with Taenia saginata was noted. PMID- 1896768 TI - Renal failure is a common complication in non-immune Europeans with Plasmodium falciparum malaria. AB - Renal failure in malaria appears to be a complication less well known than anaemia and cerebral malaria. Thirty-one non-immune patients treated for Plasmodium falciparum malaria at Hannover Medical School were reviewed. Nine patients (29%) had acute renal failure, seven of whom required dialysis, and five patients needed mechanical ventilation. Cerebral symptoms were seen in nine patients, and three of the patients died. In a second series, information about patients who died of malaria in Germany and Austria was gathered. Thirty-six reports were obtained and analysed retrospectively. Thirty-four patients (94%) had acute renal failure. Eighteen patients received dialysis while five other patients with high central venous pressure or hyperkalaemia would have benefitted from dialysis. Cerebral involvement was seen in 34 patients, and 20 patients showed respiratory failure. It was concluded that renal failure in P. falciparum malaria is as common in non-immune adults as cerebral malaria. As untreated renal failure may have a deleterious influence on cerebral and respiratory functions, early dialysis-treatment in patients with severe P. falciparum malaria and signs of deteriorating renal function is recommended. PMID- 1896769 TI - [The distribution of the tsetse fly (Diptera: Glossinidae) in the humid savanna zone (Central African Republic). Evaluation of prospective entomological techniques]. AB - Two trapping methods were compared during a survey of the distribution of tsetse flies in the Mbororo cattle breeding area of the Central African Republic: (a) several traps dispersed throughout the riverine forest galleries and remaining only one day at each site: (b) one sentinel trap placed at the cattle drinking point and remaining for several days. The latter method was more reliable and is therefore recommended. The concentration of tsetse flies at the drinking points was negligible during the rainy season. PMID- 1896770 TI - Investigation of the efficacy of flumethrin pour-on for the control of high tsetse and trypanosomiasis challenge in Kenya. AB - The effects of bi-weekly flumethrin pour-on treatments at 1 mg kg bodyweight on tsetse fly population and trypanosome infection rates were monitored over a one year period (2/89-2/90) in 2000 head of cattle on a trial farm, located in the Lamu District in East Kenya, an adjacent control farm and a transsecting road for additional fly monitoring. The tsetse fly population on the trial farm dropped from pretreatment counts of 118 flies/trap/week (Feb. 1989) to 13 in June 1989 and 32 in Jan. 1990. During the same period and months the fly population in the control farm was 90.34 and 87 flies/trap/week. Fly counts on the transsecting road, however, increased from 72.53 to 163 flies/trap/week. The impact of tsetse fly control is clearly reflected in the reduction of trypanosome infection rates on the trial farm, e.g. 37% (pre-treatment infection rate), 10% and 11% in January, June and December 1989 respectively. On the control farm the infection rates remained at distinctly higher levels of 34%, 17% and 24% during the same period. Mean weekly weight gains were 66% higher in the treated herd as compared to the untreated control herd. PMID- 1896766 TI - Serodiagnosis of echinococcosis: evaluation of two reference laboratories. AB - Two reference laboratories (CDC, Atlanta, and Institute of Hygiene, Vienna) were evaluated for their ability to diagnose echinococcosis from single serum specimens by serological assays. Out of 18 specimens, both laboratories correctly identified the 12 sera from patients with echinococcosis. Each laboratory was able to give the species diagnosis for 11 of 12 cases. The CDC abstained from giving a final species-diagnosis for a serum from a patient with alveolar echinococcosis, the Institute of Hygiene similarly, for a case of cystic echinococcosis. Our findings reveal the considerable potential of today's serological methods for primary diagnosis of infections with Echinococcus granulosus and Echinococcus multilocularis. PMID- 1896771 TI - Chemotherapy of CNS-trypanosomiasis: the combined use of the arsenicals and nitro compounds. AB - In trypanosomiasis chemotherapy the main mode of action of the nitro-compounds, including the 5-nitroimidazoles or nitrofurans (nifurtimox) is to increase the oxidative stress on the organism either directly by the production of peroxides or indirectly by "futile redox cycling". If this is the case, then these nitro compounds and the arsenicals should act in combination on the trypanothione oxidation-reduction reaction of the trypanosome. In this paper this has been demonstrated to occur with all those nitro-compounds which have exhibited reasonable trypanocidal action in monotherapy or other combination chemotherapeutic regimens. A major advantage is the short treatment period of approximately 5 days. Pretreatment with a single dose of suramin increased the efficacy of the nitroimidazole-arsenical combination. PMID- 1896772 TI - Efficacy of combination of DFMO and diminazene aceturate in the treatment of late stage Trypanosoma brucei brucei infection in rats. AB - The therapeutic activity of difluoromethylornithine and diminazene aceturate alone and in combination was investigated in albino rats with late stage Trypanosoma brucei brucei infection. The criteria used in the assessment of the trypanocidal effect of the compounds include the degree of parasitaemia, and frequency of relapse and death. DFMO (4 percent administered in drinking water for 6 days) and diminazene aceturate (10 mg per kg intraperitoneal) produced an intermittent aparasitaemia with relapse occurring in the two groups. A combination of the two agents produced a permanent cure. The combination of the two agents appear to act synergistically in the treatment of T.b. brucei C.N.S. infection in rats. PMID- 1896773 TI - Trypanosoma cruzi: localization of neuraminidase on the surface of trypomastigotes. AB - Immunoelectron microscopy (IEM) using TCN-2, a monoclonal antibody specific for Trypanosoma cruzi neuraminidase (NA), was performed to determine the precise localization of the parasite enzyme. In agreement with previous observations, TCN 2 reacted with tissue culture trypomastigotes, but not with epimastigotes, amastigotes or intracellular forms in intermediate stages of development. NA was localized on the surface of tissue culture trypomastigotes and in the Golgi apparatus suggesting that the enzyme is modified post-translationally. In agreement with this suggestion, digestion of NA with N-Glycanase, an enzyme that releases N-linked oligosaccharides, decreased the molecular weight of the polypeptides that make up NA. PMID- 1896774 TI - Surface area calculation for Onchocerca volvulus microfilariae. AB - The pathogenesis of tissue damage in filarial infections involves the generation of inflammatory mediators by interaction of parasite surfaces with the host immune response. In the presence of a heavy parasite burden, the tremendous potential for development of adverse local or systemic inflammatory responses may be appreciated by knowledge of the cumulative surface area represented by circulating microfilariae. The approximate surface area of a single microfilariae of Onchocerca volvulus was calculated using mathematical formulae for standard geometrical shapes and values derived from serial measurements of electron micrographs. Numerical values for the surface area represented by large numbers of microfilariae are given and compared to surface areas of the host which can harbor many millions of microfilariae. PMID- 1896775 TI - Low doses of quinine during a short time period are effective for clearance of Plasmodium falciparum in asymptomatic children in Guinea Bissau. AB - Asymptomatic children in Guinea Bissau were given 5 mg quinine per kg body weight two times daily for 5 days (n = 18) or 3 days (n = 20) for treatment of Plasmodium falciparum. Parasites disappeared within four days after initiation of treatment and remained absent during the first week afterwards. Six children reported adverse reactions, mainly mild tinnitus which disappeared after termination of treatment. Reduced doses of quinine for shorter treatment periods was effective in this study. Further studies in symptomatic patients are needed to elucidate whether this low-dose regimen could be an alternative to chloro quine in the treatment of P. falciparum in Africa. PMID- 1896776 TI - Absence of epidemiological inter-relations between HIV infection and African human trypanosomiasis in central Africa. PMID- 1896777 TI - Ivermectin uptake and distribution in the plasma and tissue of Sudanese and Mexican patients infected with Onchocerca volvulus. AB - Ten Sudanese patients with Onchocerca volvulus infection were treated with a single oral dose of 150 micrograms/kg of ivermectin. Plasma samples were collected before treatment, 0.5, 1, 3, 4, 6, 12 hours and 1, 2, 3, 7, and 30 days. Four patients were selected for nodulectomies and skin biopsies at 6, 18 and 30 hours and 3 days post treatment. Using these samples O. volvulus worm fragments were dissected free of host nodular tissues for ivermectin extraction. Ivermectin was present in the nodular tissue at 6 hr and persisted for 3 days. It was also detected in an individual worm tissue extract at a concentration similar to the nodule, but in subcutaneous fascial tissue higher concentrations were sometimes found. Ivermectin was detected by radioimmunoassay in the plasma of all patients at 1 hr and peak concentrations were reached in an average of 5.6 hr. The drug persisted at detectable levels for 7 days in 70% of the studied patients. Plasma samples were also collected from 16 treated Mexican onchocerciasis patients before ivermectin treatment and 4 hr treatment and from six individuals who served as controls. The Mexican patients had concentrations of ivermectin in their plasma similar to those in the Sudanese patients. PMID- 1896778 TI - Ivermectin in the treatment of onchocerciasis in Britain. AB - Thirty-one patients with onchocerciasis were treated with a single dose of 150 200 micrograms/kg ivermectin. They were observed for three days to detect acute reactions and were reassessed clinically and parasitologically three, six and twelve months after treatment. 22 patients were expatriates. All had early, light and often localised infections and were not reexposed to infection during the course of the study. 25 patients completed follow-up. Patients who relapsed were retreated with the same dose after an interval of not less than five months. Adverse reactions were less severe than those experienced by similar patients treated with diethylcarbamazine and only one patient was given corticosteroids. 17 patients (68%) relapsed within one year and two thirds of these had done so within 6 months. A similar pattern was seen after the second dose. A single dose of ivermectin, repeated every three to six months as necessary, is likely to be the treatment of choice for patients in non-endemic areas, lightly infected with Onchocerca volvulus, until a safe macrofilaricidal drug emerges. One third of such patients may be cured with each treatment. PMID- 1896779 TI - Onchocerca volvulus: characterization of monoclonal antibodies reactive with surface components of third-stage larvae. AB - Five murine monoclonal antibodies (Mab's) have been produced which are reactive with the surface of the third-stage larvae (L3) of Onchocerca volvulus. These were produced from a fusion performed after intrasplenic injection of 10 live O. volvulus L3. Hybridomas were first screened by Elisa using a PBS extract of O. volvulus female adult worms. Elisa negative wells were screened by IFA on whole formalin-fixed L3. Five Mab's were isolated which were reactive with the surface of L3, all were found to be of the IgM isotype. All five Mab's were cross reactive with the surface of O. lienalis L3, but not with the L3 of Brugia malayi, B. pahangi, Dirofilaria immitis, or Acanthocheilonema viteae. One of the Mab's, OV3-9, reacted with an antigen common to many species of helminths. The other four were genus specific reacting only with O. volvulus and O. lienalis. All 5 Mab's reacted with L2 of O. volvulus, but not with the L4 by IFA on whole fixed larvae. Only Mab's OV3-8 and OV3-9 reacted with cryosections of adult O. volvulus by IFA indicating that the other 3 Mab's are specific for the surface of L2/L3 of the genus Onchocerca. None of the Mab's reacted with detergent dissociated L3 proteins in Western Blot analysis. The ability of L3 to bind the Mab's was abolished by incubating larvae in either proteinase K or trypsin but was unaffected by incubation of larvae in detergents, or by treatment with periodate, indicating the proteinaceous nature of the Mab specific epitopes. Anti phosphorylcholine Mab (Gib-13) did not react with the surface of L3.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1896780 TI - Short-changing alcoholic patients? PMID- 1896781 TI - [Surgical treatment of ruptures of the rotator cuff]. AB - This study analyses the results of 30 surgical repairs of the rotator cuff. The basic problem was degenerative pathology in which medical treatment had been tried previously in all cases. The type of treatment was based upon preoperative evaluation and arthro-CT scan in particular. Results were invariably good, with regression of pain and recovery of activity. Muscle power was significantly correlated with the value of the tendon repaired, this being reflected overall by incomplete recovery. PMID- 1896782 TI - [Treatment of rheumatoid polyarthritis with methotrexate]. AB - This retrospective study involved 60 patients (7 men, 53 women) with rheumatoid arthritis (RA) and given methotrexate between 1985 and 1990. The mean time that RA had been present was 12 years and more than half of the patients had received more than 3 types of general treatment in the past. The mean total duration of MTX was 17.3 months, with a total dose of 790 mg. The efficacy of MTX was confirmed by a significant improvement in clinical and laboratory parameters. Treatment was withdrawn permanently in 21 cases (35% of patients). Adverse reactions, responsible for two thirds of treatment withdrawals (14/21) occurred in most instances during the first year of treatment. Hepatic toxicity was commonest. Two cases of aplasia were reported as well as 3 cases of pneumonitis, one fatal. These involved two cases of secondary infection and one of pneumonitis directly imputable to MTX. Withdrawals for inefficacy were rare, occurring in less than 10 p. cent of patients. Treatment continuation rates were 77 p. cent at 1 year, 66 p. cent at 18 months, 55 p. cent at 2 years, 42 p. cent at 3 years and 32 p. cent at 4 years. MTX is effective treatment for RA but is not free of adverse reactions, sometimes potentially fatal. Prolonged monitoring is necessary because of the sometimes delayed onset of adverse reactions. PMID- 1896783 TI - [The risk of transmission of HIV virus during orthopedic surgery and its prevention]. AB - The risk of transmission of HIV virus by blood transfusion or by bone transplant during cold orthopedic surgery has been studied on the basis of known French epidemiological data concerning the problem. The authors take the opportunity to discuss appropriate methods for limiting these risks (programmed and delayed self transfusion, sterilisation of grafts) and their own experience in this area. PMID- 1896784 TI - [Bacillary trochanteritis. Apropos of 30 cases]. AB - Tuberculous trochanteritis is rare. The authors report 30 cases, 2/3 of which were seen in sanatoria. They occurred in four cases out of five in patients with long standing tuberculosis but were sometimes the presenting feature. Development of an abscess of the trochanteric serous bursa is a virtually constant complication. Their minimal functional consequences and slow progression endow them with an apparently benign nature which masks the risk of secondary complications (4 cases of coxalgia). Radiological appearances, minimal in early forms, are currently becoming more abundant by virtue of new medical imaging techniques. Specific antibiotic therapy is adequate in two cases out of three, completed in advanced and aggressive forms by local procedures dominated by surgical excision (13 cases). PMID- 1896785 TI - [Hereditary chondrocalcinosis in Tunisia. Apropos of 3 families]. AB - Hereditary chondrocalcinosis was reported in three Tunisian families. The clinical manifestations appeared early in life and extensive radiologic involvement was apparent. The mode of inheritance seemed to be autosomal with incomplete penetrance. In one family HLA typing revealed that all affected subjects had the haplotype A1 B12 DR3. PMID- 1896786 TI - [Lumbar lordosis: radiological classification and biomechanical consequences]. AB - Various radiological parameters were measured on a lateral film taken in erect position of the lumbar spine in 55 patient with low back pain. These various parameters had inter-, intra-observer and inter-study variation coefficients of less than 3%. In patients with a positive Fergusson index ("low" or inferior lordosis), mean values of the angle of lordosis and of obliqueness of the lower vertebral plateau of L5 in relation to the horizontal were higher than in patients with a negative Fergusson index ("high" or superior lordosis), this being statistically significant. In view of the correlations found between the various parameters measured and this classification, the biomechanical consequences, which have their role to play in the management of patients with low back pain, are discussed. PMID- 1896787 TI - [Measurement of the functional capacity in rheumatoid polyarthritis: a French adaptation of the Health Assessment Questionnaire (HAQ)]. AB - The ability in performing daily life activities, as assessed with self administered questionnaire, measures the functional severity of rheumatoid arthritis (RA). The HAQ Disability Index, designed to explore RA, was translated by 3 francophone teams. Three anglophones gave a back-translation. The latters were compared with the original HAQ under the control of 2 bilingual individuals, allowing to the adjustment of the French version. The validity of this measurement tool was studied in a group of recent RA (n = 40, mean disease duration: 2.4 years), longstanding RA (n = 32, mean disease duration: 8.4 years) and controls (n = 59). The construct validity was assessed in a principal component analysis, which showed the contribution of each item of the questionnaire. The intra-subject reproducibility was satisfactory. The HAQ score correlated well with usual clinical and radiological parameters. It differed significantly in the groups, showing a high discriminant ability. A validated instrument for measuring functional ability in French RA patients is now available for the follow-up and therapeutic assessment. PMID- 1896788 TI - [Sports activity and body composition. Study by whole body osteodensitometry of 269 men between 17 and 21 years of age]. AB - Two hundred and sixty one men aged between 17 and 21 were questioned concerning their sports activities and underwent "whole body" osteodensitometry. Values found in terms of bone density rose harmoniously and proportionally from the ages of 17 to 21. Studied in terms of sports activities claimed, figures were higher in athletes and this essentially concerning the lower limbs and pelvis. These data contrast a "growth" effect with a "physical activity" effect, the first being of a systemic nature involving total bone mass and the second of a locoregional nature concerning only those bone segments involved in a particular activity. Our study failed to reveal any arguments in favour of spinal bone steal to the advantage of the lower limbs in athletes. The authors feel that "whole body" osteodensitometry by simultaneous and prospective study of bone segments involved or not involved in exercise should enable a distinction to be drawn between the systemic and locoregional effects of physical activity and thus, in the context of primary prevention, to define the optimal calcium intake and physical activity leading to acquisition of maximum bone capital and to maintain it to the best possible extent. PMID- 1896789 TI - [Dorsal radiculalgia and vertebral hyperostosis]. PMID- 1896790 TI - [Reactive arthritis and juxta-articular rheumatism in Trichomonas vaginitis]. PMID- 1896791 TI - [Association of rheumatoid polyarthritis and large granular lymphocyte lymphocytosis or pseudo-Felty's syndrome: a new case, with eosinophilia and without neutropenia]. PMID- 1896792 TI - [Shoulder pain caused by chondrosarcoma. Apropos of a case]. PMID- 1896793 TI - [Myeloma in the elderly: a retrospective study of 17 patients over a 10-year period]. PMID- 1896794 TI - [An uncommon site of osteoid osteoma: the acromion]. PMID- 1896795 TI - [The vallecula: an anatomic reality?]. AB - The vallecula epiglottica is a borderline area between the pharynx and the larynx, though covered by the epiglottis, and a functionally strategic site and breeding ground for epidermoid carcinoma, but it has remained unappreciated by anatomists. The borders of the vallecula within the oropharynx are represented by the anchoring systems of the epiglottic cartilage; the basilingual margin is sometimes inaccurate. We would like to emphasize the topographical relationships in the vallecular region, in particular: --the proximity to the base of the tongue, which is the preferred are of extension of epitheliomas, --and the features of the hyoepiglottic membrane, which is a veritable barrier for neoplastic infiltration. The valleculae epiglotticae are a definite oropharyngeal anatomical entity, and deserve the attention of maxillofacial surgeons, who should be able to suggest a surgical treatment of cancers that would be practicable both from a functional and from an oncological point of view. PMID- 1896796 TI - [Macroglossia and amyloidosis. Apropos of a case]. AB - In the present treatise, a classification scheme for macroglossia has been formulated, based on clinical and etiological features of an enlarged tongue. The pathogenesis of each form-type of macroglossia is then described. In addition to, the authors report a case of female patient suffering from macroglossia, who was admitted in their Clinic. This pathological condition was the single and the very first clinical sign (symptom) of her, and (which) led up to the diagnosis of amyloidosis. They present the procedure of the diagnosis and differential diagnosis for this patient, they emphasize their conclusions (considerations) and make comments on the coexistence or correlation of macroglossia with amyloidosis. PMID- 1896798 TI - [Schuchardt's procedure and surgery of open bite]. AB - Posterolateral segmentary maxillary impaction osteotomy has a role to play in the treatment of gaps between the upper and lower jaws. It has several advantages, especially an uncomplicated postoperative period and the single-maxillary contention it provides. The indication must be established after an articulator assessment in order to take into account the mandibular protrusion caused by autorotation and to prevent a sagittal shift. Associated marginal glossectomy will frequently be required. Similarly, in case of vertical excess, genioplasty for vertical reduction will improve the facial balance. This technique may also be proposed as "pre-prosthetic surgery" in cases of egression in the premolar and molar areas, for which it has shown excellent results. PMID- 1896797 TI - [The role of condylectomy in the treatment of mandibular laterognathism in children]. AB - In 7 cases of mandibular laterognathia caused by condylar hypertrophy, the authors specify the clinical and teleradiological features in adolescents. They emphasize the inadequacy of lateral teleradiography and of its measurements, and the need for three-dimensional investigation. In adolescents, secondary deformations, either spontaneous or therapeutic, are rare, and the treatment preferred is condylectomy based on the study of casts. The immediate results of this techniques are satisfactory. The long-term consequences on growth and temporomandibular pathology have been studied. PMID- 1896799 TI - [The shortening of the ascending ramus of the mandible in a case of Class III malocclusion with open bite]. AB - With reference to a case reported here, the authors emphasize the importance of reducing the length of the ramus of the jaw in rather exceptional forms of gaps between the upper and lower jaws with an increase in the posterior height of the face. This procedure provides more stable results and the patient's gums are no longer revealed when smiling. PMID- 1896800 TI - [Traumatic facial arteriovenous fistula]. AB - This paper gives a brief description of the aetiology, pathophysiology, diagnosis and treatment of traumatic arteriovenous communications. Traumatic arteriovenous communications of the face and scalp are rare lesions characterized by multiple endothelial-lined channels between the arterial and venous system. A swelling of the face with pulsatile tinnitus comprise the main presenting symptoms. Lesions should be delimited by arteriography unless small and localized. They are managed by complete excision and ligation of arterial feeding vessels. One case of traumatic arteriovenous communication of the face is reported. PMID- 1896801 TI - [Post-traumatic ptosis]. AB - Traumatic ptosis is most often secondary to a fasciomuscular lesion of the levator system. Less frequently, it results from the paralysis of the levator muscle due to an injury to the third pair of cranial nerves. This ptosis is observed in comminuted orbital fractures or fractures of the base of the skull involving the orbital apex, and it is then associated with oculomotor paralysis. In favorable cases seen early, repairing surgery of the levator system produces excellent results. When associated with ophthalmoplegia or corneal anesthesia, neurogenic ptosis requires a watch and wait policy. PMID- 1896802 TI - [The aging eyelid]. AB - Eyelid involution affects all the tissues of the lid, including the tarsotendinous band and the levator muscle. Dermatochalasis can be complicated by ptosis, entropion or ectropion, which must be taken into account during assessment and treatment. PMID- 1896803 TI - [Optic neuropathy of dental origin. Apropos of 4 cases]. AB - The optic neuropathy due to dental affection is rare but functionally serious. Authors report four cases of patients who have an acute dental infection with unilateral inflammation of the optic nerve. The first symptom was in all cases a sudden fall of visual acuity. The visual field is always altered. Papilloedema is observed in three eyes. The treatment is of the dental infection at first, secondly, corticosteroids are associated. An improvement is noticed in three cases. The authors discuss the physiopathology of the affection, its symptoms and treatment. PMID- 1896804 TI - [A conjunctival tumor of dental origin. Apropos of a case]. AB - One case of connective-tissue tumor with a lymphomatous appearance, secondary to chronic sinusitis with a dental origin, is reported. The main ophthalmological syndromes associated with a dental and/or sinusal involvement are described. PMID- 1896806 TI - [Osteomyelitis of the jaw and osteopetrosis]. AB - Osteopetrosis (Albers-Schonberg disease) is a rare sclerosing bone disorder in which osteomyelitis of the jaws is a frequent complication. Treatment of osteomyelitis is difficult and may lead to large resection. We report three new cases and we review the literature. PMID- 1896805 TI - [Albers-Schonger disease disclosed by maxillary osteitis. Apropos of a case in an African]. AB - The authors reported here a case of dominant form of osteopetrosis. The patient was a 28 years old man hospitalized for a mandibular osteitis consecutive to a tooth extraction. The clinical examination detected a splenomegaly. The laboratory tests showed anemia and thrombopenia. A radiographic skeletal survey detected a typical generalized osteocondensation. The authors pointed out the radiologic signs of the disease and underscored the difficulties in managing osteomyelitis of the jaw in such patients. PMID- 1896807 TI - Disordered gastric motor function in diabetes mellitus. Recent insights into prevalence, pathophysiology, clinical relevance, and treatment. PMID- 1896808 TI - The effect of polyacrylic acid polymers on small-intestinal function and permeability changes caused by indomethacin. AB - Non-steroidal anti-inflammatory drug (NSAID)-induced increased small-intestinal permeability appears to be a prerequisite for the development of NSAID enteropathy, which is a cause of much morbidity in patients with rheumatoid arthritis. We assessed, with a combined absorption-permeability test, the effects of Carbopol (a polyacrylic acid polymer capable of increasing mucus strength and viscosity) on intestinal function and whether it protected against indomethacin induced increased intestinal permeability. Using a test solution of 3-0-methyl-D glucose, D-xylose, L-rhamnose, and 51Cr-labelled ethylenediaminetetraacetic acid with 5-h urine collections for marker analyses, we tested 16 subjects, as base line, after 20 ml Carbopol 4 times daily for 4 days, after indomethacin alone (75 + 75 mg), and after coadministration of Carbopol and indomethacin. Carbopol had no significant effect on the permeation or absorption of the test substances. Indomethacin increased intestinal permeability significantly, and this was unaffected when Carbopol was coadministered with indomethacin, showing that Carbopol does not limit the immediate damage of NSAIDs on the small intestine. PMID- 1896809 TI - Final report on a placebo-controlled, double-blind, randomized, multicentre trial of cyclosporin treatment in active chronic Crohn's disease. AB - In a previous report we published the immediate results of a 3-month placebo controlled trial (n = 34) showing that cyclosporin (n = 37) has a beneficial therapeutic effect in active chronic Crohn's disease. Here we report on the final outcome of the patients. During the 3-month tapering-off period eight initially improved patients (36%) in the cyclosporin group worsened, as did six (55%) in the placebo group. The therapeutic gain of cyclosporin treatment was consistently significant during this period. It ranged from 22% to 25% (95% confidence limits, 2-46%). An outcome ranking showed that 7 patients of the cyclosporin group (19%) were substantially improved, 7 (19%) moderately improved, and 23 (62%) not improved after the tapering off. In contrast, no significant differences were seen during the 6-month follow-up period. Four patients of the cyclosporin group (11%) were substantially improved, 3 (8%) moderately improved, and 30 (81%) not improved at final follow-up. Significant interactions between cyclosporin and prednisolone treatment were demonstrated both at the end of the initial treatment period and at the end of the tapering-off period. We conclude that a short course of cyclosporin treatment does not result in long-term improvement in active chronic Crohn's disease. PMID- 1896810 TI - Gastric parietal, chief, and G-cell densities in chronic renal failure. AB - We calculated morphometrically the amount of antral gastrin-producing (G) cells and body parietal and chief cells in gastric biopsy specimens from 30 undialysed patients with chronic renal failure (CRF) and from sex- and age-matched controls. The CRF patients had raised fasting serum gastrin levels, whereas these were normal in the controls (mean, 290 +/- 283 (+/- SD) ng/l (n = 27) versus 33 +/- 36 (n = 30)). Serum gastrin values of the patients and controls correlated positively with G-cell density (r = 0.501, n = 36, p = 0.002), as did the maximal acid output of the CRF patients with parietal cell density (r = 0.617, n = 14, p = 0.019). In CRF patients the densities of G, parietal, and chief cells were higher than those in the controls (G cells, 351 +/- 151 (+/- SD) cells/mm2, n = 21 versus 211 +/- 90, n = 16, p = 0.002; parietal cells, 299 +/- 94, n = 15 versus 224 +/- 72, n = 14, p = 0.025; chief cells, 886 +/- 346, n = 15 versus 743 +/- 182, n = 14, p = 0.181). The results agree with previous findings indicating that hyposecretion of gastric acid in CRF does not derive from decreased capacity for acid secretion but rather from the inhibition of acid output. Increased parietal cell density in CRF patients gives cause to suspect that the maximum acid output might even in raised, possibly depending on the permanent hypergastrinaemic state with its trophic influence on the gastric body mucosa. PMID- 1896811 TI - Age-related change in human gastric mucosal energy metabolism. AB - Many investigators have reported a decrease in mucosal blood flow resulting in impairment of gastric mucosal energy metabolism in animal experiments. Recently, endoscopic studies using reflectance spectrophotometry and laser Doppler flowmetry have indicated that gastric mucosal blood flow in humans decreases with age. However, changes in energy metabolism in human gastric mucosa with age remains obscure. In this study, we measured adenine nucleotides in biopsy samples from human gastric mucosa, using high-performance liquid chromatography, and investigated changes in energy metabolism with age in subjects proven normal endoscopically. Energy charge (EC = (ATP + 1/2 ADP)/ATP + ADP + AMP) in the gastric antral and body mucosa showed decrease with age. When the subjects were divided into two groups, less than and more than 65 years old, the EC level was significantly lower in the latter than the former in both antral and body mucosa (0.65 +/- 0.06 versus 0.74 +/- 0.03 in the antrum, 0.73 +/- 0.04 versus 0.79 +/- 0.04 in the body) and significantly less in the antral mucosa than in body mucosa in both groups. The adenosine triphosphate (ATP) level in the older group showed a significant decrease (6.48 +/- 1.14 versus 9.63 +/- 1.92 in the antrum, 8.59 +/ 1.64 versus 10.60 +/- 2.13 in the body) compared with those less than 65 years old. In the antral mucosa of the older group the adenosine diphosphate (ADP) level was also significantly lower than that in the group less than 65. In conclusion, in the elderly, the energy metabolism in human gastric mucosa is impaired, and this may weaken their defensive mechanism. PMID- 1896812 TI - High prevalence of autoimmune liver disease in patients with multiple nuclear dot, anti-centromere, and mitotic spindle antibodies. AB - We used HEp-2 cells to compare the occurrence of multiple nuclear dot (MND), anti centromere (ACA), and mitotic spindle antibodies (MSA) in patients with primary biliary cirrhosis (PBC) (n = 32) and primary Sjogren's syndrome (n = 50). The predictive value of these antibodies for autoimmune liver disease was evaluated among patients with chronic liver or inflammatory connective tissue diseases. MND were found in 6%, ACA in 10%, and MSA in 6% of PBC sera. Among patients with primary Sjogren's syndrome, ACA were found in one, whereas another had both MND and MSA. MND were also detected in 1 of 25 sera from patients with other chronic inflammatory connective tissue diseases. Reexamination of these three patients showed evidence of PBC in two. In a blinded study of sera from 356 patients with chronic liver diseases, MND were detected in 10 (3%), ACA in 2 (0.9%), and MSA in 4 (1.2%). All patients with MND or ACA and two of four with MSA had PBC or autoimmune chronic active hepatitis, particularly of the cholestatic type. In four of these patients the liver disease had not previously been classified. We conclude that these antibodies have low sensitivity but high predictive value for autoimmune, cholestatic liver disease. PMID- 1896813 TI - The effect of the benzodiazepine antagonist flumazenil on the sequels of diazepam given before upper gastrointestinal endoscopy. A double-blind randomized trial. AB - The prolonged sedation of benzodiazepines may be inconvenient for the patient. Reversal of sedation, therefore, would be desirable. Accordingly, we assessed the efficacy of the benzodiazepine antagonist flumazenil in a placebo-controlled randomized trial including 40 adults undergoing upper gastrointestinal endoscopy under diazepam (Diazemuls) sedation. We found no significant differences between groups with regard to either performance (two tests) or duration (within 240 min) of sedation. There were no noticeable side effects. PMID- 1896814 TI - Non-mucin proteins in the matrix of human cholesterol gallstones. AB - Human cholesterol gallstones contain a pigmented organic matrix that may originate from biliary sludge. The cholesterol gallstone matrix contains mucin, bile pigments, and calcium salts. The goal of this study was to examine whether non-mucin proteins are present in the matrix of cholesterol gallstones. Matrix was prepared from cholesterol gallstones from 18 patients. Proteins were identified by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS PAGE) and by molecular sieve high-performance liquid chromatography (HPLC). Two proteins were present in each gallstone and migrated with or just adjacent to standards of bovine serum albumin on SDS-PAGE. Several additional lower molecular weight proteins were identified, but not in every gallstone. Protein fractions contained visible pigment after chloroform extraction, and pigment co-eluted with proteins on HPLC, suggesting binding of pigments to proteins in the matrix. We conclude that low molecular weight proteins are present in the cholesterol gallstone matrix. The major protein appears to be serum albumin, although definitive identification has not been established. The origin of these matrix proteins and their possible significance in the pathogenesis of cholesterol cholelithiasis is unknown. PMID- 1896815 TI - Cancer of the pancreas in Iceland. An epidemiologic and clinical study, 1974-85. AB - A retrospective study was performed of all patients diagnosed as having pancreatic cancer in Iceland during the period 1974-85 (12 years). The incidence of the disease during the period according to this study was 10.7 per 100,000 males and 9.8 per 100,000 females, with age-adjusted world standard incidences of 9.0 per 100,000 males and 6.7 per 100,000 females. A total of 301 patients were identified; adequate information could be obtained for 281 patients, and 225 (74.8%) had the diagnosis histologically confirmed. Two hundred and five patients with adenocarcinoma were accepted for detailed analysis. Of the patients with adenocarcinoma 139 (67.8%) were diagnosed at laparotomy, and 33 of them had the tumour resected, with an operative mortality of 12.1%. The cancer was located in the head of the pancreas in 102 patients (49.8%), and in 159 (77.6%) metastases were found at the time of diagnosis. The median survival time for the patients with adenocarcinoma was 95.4 days (SD +/- 11.1 days), although there were two patients in this group who were alive 5 years after diagnosis. The median survival for the total group of 281 patients was 98.3 days (SD +/- 11.0 days), although 6 of these patients lived for more than 5 years. The percentage of histologically confirmed tumours in Iceland is high compared with many previously reported studies. PMID- 1896816 TI - Influence of bilateral oophorectomy and estrogen substitution on the striated anal sphincter in adult female rats. AB - A quantitative histologic analysis of the striated anal sphincter of 24-month-old virgin female rats was performed to evaluate the effect of oophorectomy and estrogen substitution. The oophorectomized rats had a 21% (11-31%, 95% confidence limits) reduction in the cross-sectional area of the striated muscle tissue compared with controls. This was due to a reduction in the mean cross-sectional area of the muscle fiber, whereas the number of fibers was unchanged. Although the relative amount of stromal tissue was increased in the oophorectomized rats, the total stromal tissue was unchanged. No difference in the cross-sectional area of muscle tissue was found between the estrogen-substituted, oophorectomized rats and controls. This indicates that the estrogen depletion in the oophorectomized rats has induced the reduction in muscle tissue in the striated anal sphincter. PMID- 1896817 TI - Repeated intravenous bolus injections of omeprazole: effects on 24-hour intragastric pH, serum gastrin, and serum pepsinogen A and C. AB - We determined the effect of four times daily dosing with intravenous omeprazole on 24-h intragastric acidity, serum gastrin, and serum pepsinogen A and C in 10 fasting subjects (median age, 23.5 years). Two dose regimens (80-20-20-20 mg and 80-40-40-40 mg) were compared in a randomized placebo-controlled crossover study. Intragastric pH was continuously monitored during 24 h, using combined glass electrodes, and blood samples were taken every 6 h. Repeated boluses of omeprazole every 6 h significantly increased (p less than 0.01) the median 24-h intragastric pH compared with placebo (median pH, 3.7 (140 mg/day), 4.3 (200 mg/day), and 1.4 (placebo)) but failed to continuously raise pH levels above 4.0 in 8 (140 mg/day) or 9 (200 mg/day) of 10 subjects. No advantage of the 200-mg dose over the 140-mg dose was demonstrated. A cumulative effect of intravenous omeprazole was shown after repeated boluses but also a marked interindividual variation in response, which was correlated with the omeprazole area under the plasma concentration time curve. A significant elevation of serum gastrin coincided with the increased pH levels, which was followed after 12-18 h by a significant increase of both serum pepsinogens. PMID- 1896818 TI - The effects of selective and non-selective adrenoceptor blockade on the portal blood flow in patients with liver cirrhosis. AB - The effects of different types of adrenoceptor blocking agents on portal venous blood flow were studied in 10 patients with liver cirrhosis by using a duplex Doppler system. Oral atenolol (selective beta 1 blocker), propranolol (non selective beta blocker), and labetalol (non-selective adrenoceptor blocker) were compared. The drugs were administered at random at an interval of 3 days or more. Hemodynamic measurements were done before and after 1 h, 2 h, and 3 h of therapy. Atenolol and propranolol produced significant decrease in the portal vein cross sectional area, portal blood velocity, and estimated volume of the portal blood flow. The portal blood velocity decreased by 13.1 +/- 7.2% 3 h after atenolol and by 16.2 +/- 6.5% 3 h after propranolol administration (p less than 0.05). Labetalol had no significant influence on portal venous hemodynamics. These results support the hypothesis that a decrease in portal venous flow induced by beta blockers is at least partly mediated with alpha-adrenergic receptors. PMID- 1896819 TI - Cigarette smoking and the risk of colorectal adenoma in men. AB - We evaluated the effect of smoking on the risk of developing colorectal adenoma in men. The data were obtained in a case-control study of 103 men with colorectal biopsy-proven adenoma (cases) and 108 men with normal colonoscopy findings (controls). As compared with men who had never smoked, the estimated relative risk of adenoma increased with the pack-year smoking number, the average number of cigarettes per day, and the total years smoked. The estimated overall relative risk was 2.2 (95% confidence interval, 1.1 to 4.3). Adjustment for age did not alter these results. The data suggest that smokers may have a higher risk of developing colorectal adenoma than non-smokers. If these results are confirmed, they might be of direct importance for public health, since adenomas are precursors of colorectal cancer. PMID- 1896820 TI - The multi-crossover model for classifying patients as responders to a given treatment. AB - The strength and the validity of the multi-crossover model (MCO model) were investigated to optimalize the procedure for correctly classifying individual responders to a given therapy. One hundred and fifteen patients with non-ulcer dyspepsia from seven Norwegian hospitals were included in a 6-week double-blind MCO-designed trial with alternating weekly treatments with ranitidine and placebo. An individual effect score (X score) was calculated on the basis of the number of times the active drug was associated with less symptoms than the preceding or following placebo period. Patients categorized as responders (X score greater than or equal to 4) or unclassifiables (X scores = 2 or 3) after the MCO period continued single-blind active treatment for 4 weeks and were then reclassified by means of cross-tabulation of efficacy and adverse effects. Eighty five per cent of the MCO responders and 62% of the 42 MCO unclassifiables were reclassified as responders. The reclassified responders were then included in a single-blind follow-up placebo period until relapse or for a maximum of 8 weeks. The relapse rate was significantly greater (p less than 0.01) and the time to relapse significantly shorter (p less than 0.01) in the group of MCO responders than in the MCO unclassifiables. The large response and relapse rates in the group of MCO responders verify that the MCO model is a reliable method for correctly classifying responders to treatment. Our results indicate that by including patients with an X score of 3 in the definition of 'responder', the MCO model could be modified to optimalize the procedure for correct classification. PMID- 1896821 TI - Comparative study of CA-50 (time-resolved fluoroimmunoassay), Span-1, and CA19-9 in the diagnosis of pancreatic cancer. AB - The clinical diagnostic utility of CA-50 (time-resolved fluoroimmunoassay) and Span-1 was compared with that of CA19-9 by measuring their levels in sera from patients with pancreatic cancer and other diseases. In pancreatic cancer CA-50, Span-1, and CA19-9 showed similar positive rates (84%, 82%, and 81%, respectively). With regard to the ability to distinguish pancreatic cancer from chronic pancreatitis, however, the specificity of CA-50 and Span-1 was higher than that of CA19-9 (85%, 85%, and 79%, respectively). Despite the similar positive rates of CA-50 and Span-1 in pancreatic cancer, the correlation between these two markers was low. Thus, used in combination, they compensated for each other in the diagnosis of pancreatic cancer. In chronic liver diseases, serum levels of both CA-50 and Span-1 were correlated with that of biliary tract enzymes, alkaline phosphatase, and r-glutamyl transpeptidase. And these two markers were more affected by the biliary system than CA19-9, resulting in the significantly higher positive rates. In these diseases immunohistochemical study showed that all three markers were localized in the epithelial cells of the bile duct, with CA-50 and Span-1 showing a similar tissue distribution. PMID- 1896822 TI - Gastric emptying in achalasia. AB - Some investigators have postulated that patients with primary achalasia have a generalized upper gastrointestinal motility disorder. To evaluate gastric emptying in patients with primary achalasia, four patients were studied prospectively after successful brusque dilation. Gastric emptying of liquids and solids was normal in all patients. There is no defect in gastric emptying in patients with primary achalasia. PMID- 1896823 TI - Definitions of dyspepsia. AB - The definition of the term dyspepsia and of derived terms such as organic dyspepsia, functional dyspepsia, reflux-like dyspepsia, and non-ulcer dyspepsia continues to provoke controversy. In recent literature, however, it is apparent that a measure of agreement is now emerging with regard to 'dyspepsia', which is considered simply to denote episodic or persistent symptoms that include abdominal pain or discomfort and which are referable to the upper gastrointestinal tract. Particular symptom patterns may justify the use of descriptions such as reflux-like dyspepsia, ulcer-like dyspepsia, or dysmotility like dyspepsia, but these terms should not carry any implication that the symptom patterns can be attributed to particular pathogenetic processes. In many patients with dyspepsia, clinical assessment and investigation fail to identify any abnormality to which the symptoms can reasonably be attributed. The label of 'functional dyspepsia' is well-established medical parlance in these circumstances and is generally accepted as the converse of 'organic dyspepsia', which denotes dyspepsia for which a responsible disease process has been identified. PMID- 1896824 TI - Dyspepsia: organic causes and differential characteristics from functional dyspepsia. AB - Diseases presenting with dyspepsia fall into two general categories: organic and functional. Overall, most patients with dyspepsia have no underlying identifiable disease process. The diagnostic yield of organic causes is less in younger patients, and, conversely, serious organic lesions are common in elderly dyspeptic patients. The commonest organic causes of dyspepsia are peptic ulcer disease, gastroesophageal reflux, biliary tract disease, and gastric cancer. Symptoms and physical signs may help to differentiate these organic causes from functional dyspepsia but endoscopic or radiographic/ultrasound studies are usually necessary to ensure the appropriate diagnosis. Less common organic causes of dyspepsia not to be overlooked include drugs, pancreatitis, malabsorption syndromes, metabolic disorders, ischemic heart disease, and collagen vascular disorders. PMID- 1896825 TI - Geographical differences in the prevalence of dyspepsia. AB - The epidemiology of dyspepsia is reviewed with reference to the factors that affect prevalence, including definitions of the term, case mix, and selection. Period prevalence of dyspepsia in several different populations gives an average of 32%, of which 24% is accounted for by recognized ulcer disease. Dyspepsia appears to comprise about 70% of patients' gastrointestinal problems in a large prospective survey carried out in general practice in England, higher than some other estimates. The proportion of gastrointestinal disease in general practice consultations is examined, and while it accounts for about 5% of all consultations, it accounts for about 14% of patients consulting with a problem. There seems to have been a decline of 15% over 30 years. The difficulty of establishing the population prevalence of functional dyspepsia is emphasized, and several studies in which the proportion in general gastrointestinal outpatients has been measured are reviewed. Some data from a Glasgow study in which clinical histories have been recorded directly from patients by a computer system (GLADYS) show the prevalence of several common gastrointestinal symptoms in a clinic population and also of dysmotility-like dyspepsia. Such descriptive data should also be used for predicting diagnosis and for selecting patients to investigate. PMID- 1896826 TI - Secretory abnormalities in functional dyspepsia. AB - During the past 30 years much interest has been focused on gastric acid as a possible causative factor in functional dyspepsia. The similarities to duodenal ulcer with regard to the symptoms, previous reports of a high risk of subsequent ulcer development, and a growing number of clinical therapeutic trials showing a significant advantage for acid-reducing drugs over placebo--although challenged by many investigators--have all contributed to a common notion that the gastric acid may play an equally important pathogenic role in functional dyspepsia as in peptic ulcer disease. However, recent studies in patients with well-defined functional dyspepsia indicate quite clearly that hypersecretion of hydrochloric acid is a rare finding. Available data also contradict the hypothesis that patients with functional dyspepsia are abnormally sensitive to their gastric acid. Those dyspeptic individuals who benefit from antacids purchased over the counter usually do not have functional dyspepsia but rather organic diseases such as esophagitis or peptic ulcer. The association or pathophysiologic parallelism between functional dyspepsia and peptic ulcer implied by the results of some studies of functional dyspepsia in the past might be explained by unintended inclusion of overlooked or subclinical cases of peptic ulcer disease in those studies. PMID- 1896827 TI - Gastrointestinal motor disturbances in functional dyspepsia. AB - Since dyspepsia, as clinically defined, may constitute a heterogeneous group of conditions, it comes as no surprise that the pathophysiologic disturbances are diverse in character and prevalence. Furthermore, there is no convincing evidence that gastric and/or intestinal motor abnormalities differ among the clinical subgroups of dyspepsia. It is reasonable to suspect that a dyspeptic patient may have a gastrointestinal motor disturbance, since about half of them have delayed gastric emptying and antral hypomotility. However, proof of such motor disorder requires physiologic investigation. Even then, certainty as to whether motor abnormalities and symptoms have a causal relationship is often difficult to obtain. PMID- 1896828 TI - Is gastroduodenitis a cause of chronic dyspepsia? AB - The role of Helicobacter pylori infection in causing chronic dyspepsia is in need of further clarification. More well-designed prospective studies are necessary to ascertain whether and to what extent H. pylori-related chronic inflammation in the stomach and the duodenum causes dyspeptic symptoms; whether and to what extent there is a symptom cluster characteristic for H. pylori-related gastroduodenitis; whether and to what extent H. pylori infection is demonstrable in the chronic dyspeptic population; and whether and to what extent H. pylori infection interferes with gastrin homoeostasis and acid secretion or induces motor disturbances. Well-designed prospective H. pylori-eradication studies may further contribute in unravelling its role in chronic dyspepsia, especially in patients with active polymorphonuclear gastroduodenitis and hyperacidity. PMID- 1896829 TI - Stress and psychologic and environmental factors in functional dyspepsia. AB - Patients with functional dyspepsia are a heterogeneous group in whom psychologic and environmental factors and stress may contribute to their reports of symptoms. There is no unique personality profile in patients with functional dyspepsia. Although they have more anxiety, neuroticism, and depression than healthy subjects, their personality scores are no different than other patients with chronic abdominal pain syndromes, be they organic or functional in nature. Social factors including older age, male gender, unmarried status, and social incongruity are associated with increased frequency and severity of symptoms but not health-care-seeking behavior. Childhood role models with abdominal pain and the tendency to perceive negative life events as having great impact on their lives may affect the coping skills of these patients. Although patients with functional dyspepsia react to acute experimental stress with gastric physiologic changes similar to healthy subjects, their visceral pain thresholds are lower, which may contribute to their reports of symptoms. Despite common beliefs, most environmental factors such as smoking, alcohol, coffee, or use of nonsteroidal anti-inflammatory drugs are not important contributors to these patients' symptoms. PMID- 1896830 TI - Drug treatment of functional dyspepsia. AB - The therapeutic principles that have been applied to patients with peptic ulceration have often also been applied to those with functional dyspepsia, who by definition have no evidence of a structural or biochemical explanation for their symptoms. Treatments offered have included prokinetic drugs, anticholinergics, antacids, H2-receptor antagonists, selective muscarinic M1 receptor blockers, sucralfate, bismuth, antibiotics, and even surgery. The large range of therapies prescribed reflects the uncertainty about pathogenesis and the lack of a satisfactory treatment. Patients with functional dyspepsia should not be lumped into one broad category; treatment needs to be individualized. Certain subgroups of patients with functional dyspepsia may respond to some drug classes, whereas others may not be efficacious, although this remains to be established. The results of therapeutic studies are critically evaluated in this review. PMID- 1896831 TI - Therapeutic trial in dyspepsia: its role in the primary care setting. AB - Owing to the vast proportions of the dyspeptic patient population, it is not practicable to initiate diagnostic investigations immediately in every single patient who presents with dyspepsia. The risks associated with postponing definite diagnosis 4-8 weeks in dyspeptic patients aged less than 45 years are exceedingly small. Therefore, empiric therapeutic trial without a firm diagnosis is an acceptable alternative in those age groups. Those who recover during the course of the trial are spared the costs and inconvenience of invasive tests. Possible adverse consequences for the patients are minimized if the therapy covers those organic diseases that may cause complications (such as peptic ulcer and esophagitis). The concept of diagnosis-free therapeutic trials presupposes, however, that a sufficiently large number of patients are cured and that their need of investigation is permanently eliminated. If not, inevitable investigations are only postponed. In those patients the costs will thereby not only be the same as if early investigation had been carried out, but the total costs may in fact increase in a longer perspective owing to suboptimal management in the period before a firm diagnosis has been established. Thus, the ideal strategy would be to treat those who have a high probability of recovering during the ensuing 6-8 weeks and to investigate those in whom a prolonged course is anticipated. An empiric therapeutic trial must be followed by a thorough evaluation within 8 weeks. PMID- 1896832 TI - Spectrum of chronic dyspepsia in the presence of the irritable bowel syndrome. AB - The irritable bowel syndrome is characterized by the presence of abdominal pain associated with disturbed defecation; certain symptoms are able to discriminate the irritable bowel syndrome from organic disease. Functional dyspepsia is also common in patients with symptoms otherwise compatible with the irritable bowel syndrome. Approximately one-third of patients with functional dyspepsia have symptoms thought to be of colonic origin. Despite this, functional dyspepsia can be distinguished from the irritable bowel syndrome on the basis of symptom criteria. A generalized motility disturbance may explain the presence of dyspepsia in patients with the irritable bowel syndrome. Whether a specific type of dyspepsia occurs in this syndrome is not established. PMID- 1896833 TI - When and how to investigate the dyspeptic patient. AB - When and how to investigate the dyspeptic patient is an issue that requires careful analysis and excludes dogmatic assertions. There are several key decision factors that must be considered on a case-by-case basis: who is the patient, what kind of physician cares for the patient, and what level of uncertainty are both patient and physician prepared to accept? These factors determine to a large extent whether reassurance only, a therapeutic trial, or diagnostic investigation will be carried out. The latter may also be stratified at two levels: a basic level at which the aim to exclude major organic disease as the cause of dyspeptic symptoms and a higher level at which more complex imaging and physiologic tests would be carried out to achieve a more precise diagnosis. PMID- 1896834 TI - Effects of a single session of prolonged plantarflexor stretch on muscle activations during gait in spastic cerebral palsy. AB - Activations of the triceps surae (TS) and tibialis anterior (TA) muscles during gait were studied in children with spastic cerebral palsy (CP) immediately before and after 30 min of standing on a tilt-table with the ankle dorsiflexed to stretch the TS in the experimental group (n = 8) or after a rest period in the control group (n = 11). The EMG activity from the TS and TA was recorded concomitantly with electronic footswitch signals by a computer. Video records were made of the sagittal gait movements. Effects of PMS were determined by comparing change scores for selected spatiotemporal and muscle activation parameters between the groups. The change scores defined for the muscle activations were: a post-test/pre-test ratio of the EMG activity in specific segments of the gait cycle and a locomotor spasticity index. PMS did not significantly (p greater than 0.05) affect any of the spatiotemporal parameters nor did it alter any of the TS and most of the TA activation parameters or the SI indexes for the TS and TA. Only the TA post/pre activation ratio for the 0-16% segment of the gait cycle was smaller (p less than 0.01), indicating a decrease in TA activation post-PMS. PMID- 1896835 TI - Compensatory muscle activity for sitting posture during upper extremity task performance in paraplegic persons. AB - Compensation for the loss of postural activity of the erector spinae (ES) muscle in spinal cord injured (SCI) subjects was investigated. All SCI subjects had clinically complete lesions below the T3 level. Body disbalance was invoked by requiring sitting subjects to execute reaching movements over individually predetermined distances in a horizontal plane. Myoelectric activity of the latissimus dorsi (LD) muscle and the trapezius pars ascendens (TPA) muscle both in the SCI subjects and in controls was recorded. The body disbalance was measured in terms of changes in the position of the body centre of gravity. The effects of anticipation for body displacement were examined by cuing the direction of the reaching movement. Our results indicate that paraplegic subjects use both LD and TPA to stabilize their sitting posture, in contrast to non disabled persons. Secondly, the movement anticipation is in general slower in persons with paraplegia. Furthermore, the paraplegic subjects showed considerable impairments concerning the processing of precued information prior to a goal directed upper extremity movement. PMID- 1896836 TI - [Fish and their significance from the international and Swiss viewpoints]. AB - In landlocked countries, the role of fish is often poorly known and/or propagated. In many countries fish represent the biggest and qualitatively most valuable protein source (24% of the worldwide available animal protein) for human consumption. At present the economic significance of the production and trade of fish is already very high. However, according to FAO, the future demand of proteins can only be covered by a considerable expansion of the aquaculture production, in particular because of a stagnated fish catch and a continuous reduction of the agricultural production. The ideational value of ornamental fish appears obvious however pet fish keeping represents also a value worth of many millions US dollars worldwide. Finally the importance of fish will not only increase for economic, but certainly also for ecological reasons, because it is well established as an incorruptible bioindicator of our environment. PMID- 1896837 TI - [Clinical electroretinography in the dog. Part 1]. AB - In the first of three parts of this investigation the clinical importance and the principal indications for electroretinography are presented. The histology and ultrastructure of the retina with special emphasis on the photoreceptors and the second order neurons are discussed. A section is devoted to the history of electroretinography in man and animals. The components of the ERG and their origin are discussed. PMID- 1896838 TI - [Involution and redevelopment of the mammary gland in goats. Histological histochemical studies after a lactation time of 8-10 months]. AB - 7 chamois-coloured mountain goats were used to investigate histologically and histochemically the processes of involution and redevelopment of the mammary gland after a lactation period of 8 to 10 months. Tissue specimens were obtained by incision biopsy at drying-off two months prepartum and afterwards in intervals of 8-16 days up to parturition. The findings of this investigation were compared with results of two former investigations, in which involution and proliferation of the gland were studied separately, thus precluding an overlapping of the two processes. At drying-off, after an 8 to 10 month-lactation, sections indicative of active lactation occurred concomitantly with sections at various stages of involution, as well as early stages of redeveloping alveoli. At 16 days post drying-off, the sections indicating lactation at first examination were in a stage of maximum involution and transformation. Thus, the time required for involution was reduced by half compared to drying-off at peak lactation. At 32 days post drying-off, stages of proliferation predominated with only a few involuting glands. Specimens obtained thereafter contained only redeveloping glands. The histological and histochemical differentiation between areas of involution and those of proliferation may present difficulties during the mid portion of the dry period. There appears to be an association between the length of the time interval from drying-off to parturition and the rate of tissue transformation in the caprine mammary gland; the rate is increased when the duration of the dry period is reduced. PMID- 1896839 TI - [What is your diagnosis? Which treatment do you suggest? Splintered fracture with development of a sequester case in the left metacarpus]. PMID- 1896840 TI - Misconduct: Caltech's trial by fire. PMID- 1896841 TI - Draft of Gallo report sees the light of day. PMID- 1896842 TI - USDA's food survey riddled with flaws. PMID- 1896843 TI - A new buzz in the medfly debate. PMID- 1896844 TI - The promiscuous boy-next-door. PMID- 1896845 TI - Straightening out the protein folding puzzle. PMID- 1896846 TI - Fetal brain signals time for birth. PMID- 1896847 TI - Recognition of DNA by Cys2,His2 zinc fingers. PMID- 1896848 TI - Establishment of the Mediterranean fruit fly in California. AB - Principles of invasion biology are brought to bear on the question of whether the medfly is established in California. Since its first discovery in 1975, the pest has been captured in the Los Angeles Basin in nine separate years including every year from 1986 through 1990. The trend has become distinct--the intervals between captures are decreasing, the numbers captured are increasing, and the area over which they are detected is expanding. In addition, appearances are seasonal and captures in recent years have occurred in many of the same cities and neighborhoods where medflies were found several years before. Evidence suggests that the medfly may be established in the Los Angeles area and that previous eradication programs did not eradicate the medfly from California. It follows that detection, exclusion, and eradication protocols may need to be reexamined. PMID- 1896849 TI - The medial temporal lobe memory system. AB - Studies of human amnesia and studies of an animal model of human amnesia in the monkey have identified the anatomical components of the brain system for memory in the medial temporal lobe and have illuminated its function. This neural system consists of the hippocampus and adjacent, anatomically related cortex, including entorhinal, perirhinal, and parahippocampal cortices. These structures, presumably by virtue of their widespread and reciprocal connections with neocortex, are essential for establishing long-term memory for facts and events (declarative memory). The medial temporal lobe memory system is needed to bind together the distributed storage sites in neocortex that represent a whole memory. However, the role of this system is only temporary. As time passes after learning, memory stored in neocortex gradually becomes independent of medial temporal lobe structures. PMID- 1896850 TI - Fragile X gene. PMID- 1896851 TI - Saving aboriginal DNA. PMID- 1896852 TI - Wave of the future. PMID- 1896854 TI - New journal will publish without paper. PMID- 1896853 TI - France set to reopen AIDS pact? PMID- 1896856 TI - Healy uses wit to woo NIHers. PMID- 1896855 TI - Another sex survey bites the dust. PMID- 1896857 TI - AIDS parley site set. PMID- 1896858 TI - Will "DNA chip" speed genome initiative? PMID- 1896859 TI - Space may be bad for your health. PMID- 1896860 TI - [The 50th anniversary of the Francisco Gentil School of Nursing]. PMID- 1896861 TI - [The role of nurses in the year 2000 and beyond]. PMID- 1896863 TI - [Nursing on the masculine side]. PMID- 1896864 TI - [The year 2000--will a Europe without smokers be possible?]. PMID- 1896862 TI - [Portuguese society in the 90s]. PMID- 1896865 TI - [Smoking: the nicotine-drug interaction]. PMID- 1896866 TI - [7 reflexions on deontology]. PMID- 1896867 TI - [The appraisals of a patient who is a nurse...]. PMID- 1896868 TI - [How to lose the fear of escorting transferred patients]. PMID- 1896869 TI - [Why be anxious about intravenous fluids]. PMID- 1896870 TI - [The humanization of care. It comes up many times ... this will help!]. PMID- 1896871 TI - Imaging of the absent cervical pedicle. AB - The absent cervical pedicle is an interesting congenital anomaly which has been described in several previous case reports. Of primary importance is its recognition to avoid confusion with more clinically significant abnormalities such as fracture or an enlarged neural foramen. Although many cases can be diagnosed from the plain radiographic findings alone, it is occasionally necessary to employ another imaging modality for more definitive evaluation. We describe two cases of absent cervical pedicle imaged with computed tomography and magnetic resonance imaging. PMID- 1896872 TI - Femoral infarction following intraarterial chemotherapy for osteosarcoma of the leg: a possible pitfall in magnetic resonance imaging. AB - Bone infarction of the distal femur is reported in two patients with osteosarcoma of the leg (1 tibia, 1 fibula) treated by preoperative chemotherapy including intraarterial chemotherapy (IAC) by Cis-platinum. Both patients were examined by magnetic resonance imaging before chemotherapy and again prior to limb salvage surgery. The location of these lesions in the distal femur must suggest bone infarction especially if the tumor has decreased in size under treatment. PMID- 1896873 TI - Time-dependent scar enhancement in magnetic resonance imaging of the postoperative lumbar spine. AB - Magnetic resonance imaging (MRI) has become a principal modality in the evaluation of the post-operative lumbar spine. Gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) can often facilitate differentiation of scar from recurrent disc herniation according to established criteria. Scar has been believed to enhance predictably. We reviewed the contrast-enhanced MR scans of 44 patients who were examined for recurrent back pain following disc surgery and attempted to assess the enhancement characteristics of scar as a function of the time interval between initial surgery and the imaging study. In 44 patients, scar was believed to be present at 32 of 49 disc levels. The degree of enhancement was related to the postoperative interval; those studies performed no later than 9 months after surgery tended to exhibit the greatest degree of enhancement. Surgical confirmation of these MRI findings was available in 12 patients. In patients examined long after surgery, scar enhancement may be less intense than in those examined shortly after surgery, or even nonexistent. This temporal factor should be considered when using contrast material to differentiate scar from recurrent disc herniation in post-operative examinations of the lumbar spine. PMID- 1896874 TI - Antley-Bixler syndrome: description of two patients. AB - The Antley-Bixler syndrome comprises malformations of cartilage and bone. The essential signs are a dysmorphic facies with flattening of the central region of the face, humeroradial synostosis with flexed attitude of the upper limbs and swelling of the distal interphalangeal and metacarpophalangeal articulations. Congenital atresia of the nasal choanae, which is often present, makes the prognosis of this syndrome extremely severe. Two patients affected by the syndrome are described. Atresia of the nasal choanae was absent in both. The first patient had genital ambiguity, a condition which has been described in the literature in only two other cases; the second one had all the fundamental characteristics of the syndrome except for humeroradial synostosis, although hypoplasia of the lateral condyle of the humerus and dislocation of the radius are present in association with synostosis between the 2nd metatarsal and the intermediate cuneiform. PMID- 1896876 TI - Metrical variation in the thumb, index, and middle finger among four samples of both sexes. AB - Metrical length and width parameters of the first through third ray metacarpals and phalanges are presented for four samples of adults of both sexes drawn from radiographs of the Ten State Nutrition Survey (1968-1970). Radiographic measurements were obtained with the aid of a digitizer and computer translation program. The establishment of ranges of variation among these samples allows their use in clinical diagnosis, for example of syndromes via pattern profile analysis. Proportional analyses of hand metrics can now be extended to include widths of the first three rays as well as lengths, and data for such a purpose are now available for American blacks. Mexican-Americans, and Oriental-Americans in addition to American white groups. Examples of intersample variation are given; the need to consider such variation in clinical contexts is emphasized. PMID- 1896875 TI - Physical bone changes in carragheenin-induced arthritis evaluated by quantitative computed tomography. AB - Repeated non-invasive measurements were performed in dogs of trabecular bone density (TBD), low density bone area (LDBA), and high density bone area (HDBA) in chronic arthritis using quantitative computed tomography (QCT). Unilateral chronic arthritis of the knee had been induced by weekly instillation of 2 ml carragheenin into the right knee joint for 12 weeks with the left knee serving as a control. CT scanning of the distal femoral condyles was performed in 12 mature dogs with chronic arthritis. Another 6 dogs underwent a longitudinal CT study starting immediately prior to induction of arthritis. During induction of arthritis TBD decreased (P less than 0.01), LDBA increased (P less than 0.05) and HDBA decreased (P less than 0.01) in the arthritic bone. Opposite changes were found on the control side, i.e. TBD increased (P less than 0.01), LDBA decreased (P less than 0.01) and HDBA increased (P less than 0.01). The chronic arthropathic bone showed 20% lower TBD (P less than 0.0001), greater LDBA (P less than 0.0001) and lower HDBA (P less than 0.0001) as compared with the control bone. Reproducibility tests of TBD showed a coefficient of variation of 0.8%. Indentation tests and histomorphometric analyses confirmed the bone density changes as measured by CT. PMID- 1896878 TI - Case report 661. Hemophiliac bleed into a separate suprapatellar pouch (due to persistent plica). PMID- 1896877 TI - Upper humeral cortical thickness as an indicator of osteopenia: diagnostic significance in solitary myeloma of bone. AB - Solitary myeloma of bone is a form of plasma cell tumor, histologically indistinguishable from multiple myeloma but characterised by a single bony focus of disease. Most patients respond to local radiotherapy (median survival 10-12 years); however, many (greater than 30%) rapidly develop multiple myeloma (median survival 2-4 years). Currently, no criteria exist for identifying these high-risk patients at the time of diagnosis. We have assessed the prognostic value of clinical features at presentation in 32 patients with solitary myeloma of bone. Only osteopenia at presentation (P less than 0.000003) and immunoparesis (P less than 0.00002) proved to be independent, significant prognosticators of decreased survival. Exclusion of patients with osteopenia or immunoparesis at presentation identified a group with an 80%-90% chance of surviving 10 years. Patients with either risk factor had a median survival of only 27 months. Osteopenia was assessed using measurements of combined cortical thickness in the upper humerus. This site has not previously been used, and normal values are presented for a control group (n = 413). PMID- 1896879 TI - Case report 677. Intraarticular ganglion arising from the posterior cruciate ligament. PMID- 1896880 TI - Case report 678. Sporotrichal arthritis. AB - A case of articular sporotrichosis occurring in the wrist and ankle of a 39-year old man is reported. Review of the literature on this disorder confirms the diagnostic difficulties presented by this usually chronic, progressive, fungal arthritis. The diagnosis of this entity should be considered in the evaluation of any patient presenting with a progressive destructive arthritic process. The pathological and radiological features of a typical case are discussed and the mechanisms of infection and type of individual affected by this disease are described. PMID- 1896881 TI - Case report 679. Central low-grade osteosarcoma with foci of dedifferentiation. AB - An infrequently encountered case of well-differentiated CLOS containing dedifferentiated tumor foci in a 28-year-old Japanese man is reported. The patient died from widespread metastases with a microscopic appearance identical to the anaplastic dedifferentiated lesions of the original tumor. This is, to our knowledge, the first report of a case of CLOS with dedifferentiation at the time of initial surgery. The literature concerning CLOS was reviewed and the diagnostic features of CLOS discussed. PMID- 1896882 TI - Case report 680. Intraosseous meningioma of the sphenoid bone. AB - Two cases of intraosseous meningioma of the calvaria with hyperostosis are presented and compared with the appearance on plain films and CT of en plaque meningioma, metastatic disease from such primary sites as prostatic cancer, and fibrous dysplasia. It is emphasized that intraosseous meningioma in the calvaria is relatively uncommon, occurring most often in the sphenoid bone (probably because of its numerous articulations). The relationship of the development of intraosseous meningioma to the entrapment of dura containing arachnoid cells is discussed in considering the cause of such lesions, and it is stressed that calvarial fractures and cranial sutures may contribute to the entrapment of arachnoidal tissue and later the formation of a meningioma. PMID- 1896883 TI - Case report 682. Neuroepithelioma of soft tissues of the knee. AB - Peripheral neuroepitheliomas should be included in the differential diagnosis of a soft-tissue tumor in the extremities or chest wall, especially in young adolescents. MRI provides useful information as to the extent of the tumor and relationship with adjacent structures, although it may not differentiate neuroepitheliomas from other, more common, soft-tissue sarcomas. Together with clinical and histological findings, MRI can assist in the diagnosis and treatment planning of this tumor. PMID- 1896884 TI - Case report 683. Distal metaphyseal femoral defect (cortical desmoid; distal femoral cortical irregularity). PMID- 1896885 TI - Case report 684. Infantile myofibromatosis. AB - A 4-year-old boy presented with a mass in the left groin. Radiographic examination demonstrated that the soft-tissue mass contained calcification and was encroaching on the left femur. The pre-biopsy clinico-radiographic diagnosis was that of some sort of sarcoma. The pathological findings identified the mass as infantile myofibromatosis. This case serves to stress the need for greater caution in the clinico-radiographic diagnosis of soft-tissue tumors. PMID- 1896886 TI - Case report 685. A huge tumor in the right upper arm. PMID- 1896887 TI - Incarceration, coping, and support. AB - Data are presented from a study of the effects of incarceration on family life involving 63 inmates and 38 inmate wives. Inmates and wives who participated in the Family Reunion (conjugal visit) Program were contrasted with matched, nonparticipating inmates and wives. Interview data and standardized measures were used to assess inmate and wife coping and support to the wife. Coping was in the normal range for both groups of inmates and wives and, except for measures of wives' passive appraisal, did not differ according to Family Reunion Program participation. Wives used a variety of coping strategies, most commonly family support and religion, and had substantial contact with extended families, with most receiving practical help and emotional support from extended families and neighbors. Implications for clinical intervention are discussed. PMID- 1896888 TI - Reunions between adoptees and birth parents: the adoptees' experience. AB - One hundred fourteen adult adoptees who had reunions with their birth parents responded to a mail questionnaire about these reunions. Some had been found by their birth parent, and others had searched for this parent. Those who searched were stimulated to do so by a life-cycle transition, by a need to get background information, and by a need to complete their sense of identity. For most of these adoptees, their self-esteem improved and their relationship with their adoptive parents was strengthened as a result of the reunion. These respondents advocate open adoption and better preparation for the adoptive family about adoptees' need to connect with their birth families. PMID- 1896889 TI - [Suicide and geomagnetic activity]. AB - The study presents the results of the influence of geomagnetic activity on the suicide rate. The authors correlated the incidence of suicides submitted to post mortem examinations in the Institute of Forensic Medicine, Comenius University Bratislava during the period 1985-1987 and geomagnetic activity. It was revealed that the most adverse periods are the days of a drop or minimal geomagnetic activity. A total of 347 suicides committed by men and women were analyzed. On the days of drop or minimal geomagnetic activity 73% of the suicides were committed. During the stage of drop or minimal geomagnetic activity there was one suicide in 2,51 days, during the rise and maximal stage there was one suicide per 4,88 days, i.e. almost double the time. The partial results for individual years are similar to the summary results. The results are supported also by quoted data from other independent research projects (injury rate of sportsmen, fatal work injuries, alcoholism); in the context with the latter the authors point to the fact that for man periods with a decline or minimal level of geomagnetic activity are less favourable and more dangerous than periods of rising or maximum activity. In the conclusion the author outlines the possibility to apply the assembled findings in preventive medicine. PMID- 1896890 TI - [Simplification of combined thin-layer chromatography/infra-red spectroscopy using Silufol plates]. AB - A simplified method for combining thin layer chromatography and infrared spectroscopy was developed. It concentrated compounds in separation just on the treated original chromatogram (after a special cutting out zones). Reduced number of operations substantially decreased losses of studied substances. Minimal amount of a substance for producing the spectrum was about 30 micrograms. PMID- 1896891 TI - [Resection of the internal carotid artery and its replacement with a vein graft (possibilities of using this method in various conditions)]. AB - The author describes his experience with 51 reconstructions of the internal carotid artery made on account of different indications by the method of resection and substitution by venous graft. He draws attention to the fact that this method is the method of choice in some special morphological findings, in others it can be considered an alternative method beside much more frequently used endarterectomy. The author draws attention to some advantages of the method on account of which it holds a firm place in the series of reconstruction operations used by vascular surgeons. PMID- 1896892 TI - [The role of computer tomography in the diagnosis of aneurysms of the abdominal aorta]. AB - The advantages of computer tomography are obvious. They include the non-invasive character of examination, the detection of aneurysms with a small diameter and the opportunity to check them systematically. Computer tomography is in the authors' opinion most effective in the differential diagnosis and for the assessment of the character of aneurysms--stable or unstable, and in particular in the diagnosis of initial stages of ruptures. PMID- 1896893 TI - [Traumatic rupture of the thoracic aorta as part of a multiple injury]. AB - The authors submit case-histories of four patients with traumatic ruptures of the aorta where the patients survived for 1-10 days. All cases were fatal. The general condition of the patients did not permit surgical operation. The survival time of the patients provides evidence that in rupture of the aorta it is in some instances possible to make inevitable examinations and operations. If time permits, then transport to a specialized department is indicated. The operation requires satisfactory approach and availability of extracorporeal circulation. PMID- 1896894 TI - [Localized benign pleural mesothelioma]. AB - The authors describe a case of benign mesothelioma of the pleura. This is a not very frequently encountered condition which as a rule is diagnosed only on the basis of histological examination of a preparation taken during operation. The surgical operation is most frequently indicated on account of the diagnosis of a lung tumour. If this diagnosis is taken into consideration and the patient's diagnosis is made in time and the patient is operated, the subsequent prognosis is very favourable. PMID- 1896895 TI - [Late complications of unrecognized post-traumatic diaphragmatic hernias]. AB - The authors reflect, based on two case-histories, on problems of diagnosis and operation of undiagnosed post-traumatic diaphragmatic hernias. In one instance a perforation of the diaphragm was missed during operation of a piercing heart injury and in the second case the operation was made only after incarceration of the stomach and spleen one year after a blunt chest injury. PMID- 1896896 TI - [Perforation of Meckel's diverticulum by a foreign body]. AB - The authors describe two case-histories of acute abdomen which developed as a result of perforation of Meckel's diverticulum by a foreign body. They draw attention to diagnostic difficulties by a foreign body. They draw attention to diagnostic difficulties and the frequent diagnosis of acute appendicitis. PMID- 1896897 TI - [Subcapsular hematoma--a grade I liver injury]. AB - The authors give an account of 11 patients hospitalized in 1975-1988 in the Traumatological Research Institute in Brno with a subcapsular haematoma of the liver. In case of suspected liver injury they use nowadays examination by ultrasound. Laparotomy must not be delayed in patients with unstable vital functions only because of various diagnostic examinations. The therapeutic success in liver injuries depends on early operation, correct resuscitation and selection of an optimal surgical procedure which depends above all on the type and grade of severity of the injury. PMID- 1896898 TI - [Surgical treatment of necrotizing hemorrhagic pancreatitis with a prolonged course]. AB - The authors describe the course of acute haemorrhagic necrotizing pancreatitis complicated by prolonged septicaemia, the formation of abscesses, acute haemorrhage and a intestinal fistula--"Critically ill patient". Early surgical elimination of necrotic septic foci is the prerequisite of effective treatment and cure. In the diagnosis CT and magnetic resonance prove most useful. With the latter so far little experience as been assembled. Ultrasonographic visualization technique is insufficient for the diagnosis of focal changes in the area of the pancreas. PMID- 1896900 TI - [Extracorporeal lithotripsy--a new possibility in the treatment of gallstones?]. AB - In the submitted review the author presents the results of treatment of cholelithiasis by extracorporeal lithotripsy by shock waves. Provided there is strict selection of patients with 1-3 cholesterol concrements in the gallbladder, treatment is successful in 70-90%. Complications occur in cca one third of the patients, the mortality rate is zero. The author gives criteria for indication which are met by cca 15-20% patients with cholelithiasis. In the discussion the author analyzes possibilities of urgent and preventive lithotripsy of gallstones, the number of relapses and biological effectiveness of shock sound waves, problems of competence and the economic effect of treatment. PMID- 1896899 TI - [Liver abscess after elective cholecystectomy]. AB - The authors submit the case-history of a 39-year-old patient with elective cholecystectomy where the immediate postoperative course was complicated by a liver abscess. The authors discuss aetiological factors, diagnosis and treatment of liver abscesses. In the conclusion they submit a proposal of ATB prophylaxis in severe inflammations of the gallbladder and biliary pathways. In the department of the authors ATB prophylaxis is not used before elective cholecystectomy. PMID- 1896902 TI - [Directed photonucleolysis of the intervertebral disk and its herniation. Preparation for percutaneous laser diskectomy]. AB - Under model conditions it proved possible, using a whole-body stereotactic apparatus, to focus on a human intervertebral disc and its prolapses and eliminate them by photocoagulation, using a laser. The suitable cannulae have a 3 mm diameter and an output of 6 to 12 W. The necessary lesion is reached in a fractionated manner within 1 minute. Thus the conditions were created for the new technique of percutaneous disectomy which has been done hitherto by means of chemical substances or mechanically by incision and suction. PMID- 1896901 TI - [Problems in perineal wound healing after abdominoperineal excision of the rectum per primam]. AB - The authors analyze different methods of treatment of perineal wounds after abdominoperineal extirpation of the rectum. They do not recommend for wider use the method of filling the cavity with an omental flap or loops of the small intestine. They consider haemostatic tamponades of the perineal cavity as obsolete in view of the large number of postoperative infectious complications. In their trials they used as a filling absorbable polymer. They elaborated a method of lavage drainage of the perineal wound which, in view of the favourable results achieved, is considered the method of choice. PMID- 1896903 TI - [Prolonged epidural hemorrhage]. AB - The authors give an account of four male patients aged 4, 26, 34 and 51 years where they removed on the 4th to 20th day following head injury an epidural haematoma. In the youngest patient the haematoma was in the area of the posterior cranial fossa on the left in another patient on the left in the occipital area, in the third patient concurrent epidural and subdural haemorrhage in the left temporal region was involved as well as contusion of the brain on the same side, in the last patient a large epidural parieto-occipital haematoma on the right side was involved. In the four-year-old boy the haemorrhage developed without fracture of the skull, in the remainder there was fracture of the skull, its course was, however, so inconspicuous that with the exception of one it was found only on operation. Although the clinical symptoms in all patients suggested that a posttraumatic intracranial complication is involved, CT helped to establish the correct diagnosis. All four patients are alive, three without an obvious neurological deficit, one suffers from mild hemiparesis. PMID- 1896904 TI - [Possibilities and results of surgical treatment of vertebro-basilar insufficiency associated with atherosclerosis of the extracranial cerebral arteries]. AB - The author describes his experience with the surgical treatment of processes leading to the syndrome of vertebrobasilar insufficiency. He differentiates between direct interventions focused primarily on the reconstruction of the pathologically altered vertebral artery. Interventions of the indirect type influence the vertebro-basilar insufficiency by modifying the deviated blood stream from the vertebrobasilar area. The author emphasizes reimplantation methods, as compared with desobliterations. PMID- 1896905 TI - [Treatment of injuries of the cervical spine]. AB - Injuries of the cervical spine are re-evaluated at present. New surgical procedures and research on the stability, when these procedures are used, caused that surgical treatment is used more frequently. Attention is draw to provisions in the field as well as in hospitals, on the diagnostic approach and classification of these injuries, on the procedure of conservative surgical treatment. The domain of conservative treatment are injuries of the upper cervical spine (C1 and C2); injuries of the lower cervical spine are frequently unstable, and therefore frequently indicated for operation. Attention is drawn to modern views on surgical treatment of comminuted fractures of the atlas and the dens axis. The authors analyzed their own material from 1986 to April 30, 1989 and in case-histories of three patients they draw attention to their therapeutic method. The authors demonstrate their own modified plates for the anterior stabilization of the cervical spine and their modification of the Halo device "Halo Vest". They discuss biomechanical properties of posterior and anterior stabilization methods. PMID- 1896906 TI - [Injuries of the diaphragm]. AB - The authors submit a group of 11 patients treated in 1977-1988 on account of traumatic injury of the diaphragm. The group comprised 9 adults and two children. The authors analyzed the causes of injury, the condition of the patients on admission to hospital, the interval between admission and surgical treatment of the diaphragm, the diagnostic approach, the surgical approach and its results. PMID- 1896907 TI - [Selection of correct treatment in patients with low cardiac output after open heart surgery]. AB - In operations of the open heart inadequate cardiac output can lead to the so called syndrome of a low cardiac output. The main indicator of cardiac function is the cardiac index. In patients in a critical state reduction of the cardiac index below 1.9 l/min q.m. suggests the presence of this syndrome. The submitted paper deals with the early detection of a low cardiac output which makes it possible to select optimal treatment before clinical signs of failure as well as further complications develop. The submitted paper deals with a group of 115 operated patients incl. 53 operated on account of IHD and 62 on account of rheumatic heart disease. Treatment was according to haemodynamic values divided into four groups: 1. Insurance of an optimal intravascular volume without pharmacological support, 2. pharmacological support of vasodilatating agents (nitroglycerine, sodium nitroprusside), 3. positive inotropic support by dobutamine, 4. support by a combination of vasodilatating agents and positive inotropic pharmaceutical preparations (dobutamine, dopamine). The favourable effect of treatment in the above groups is apparent already after four hours, and after 20 hours the investigated values shift to an optimal zone. The authors emphasize the high diagnostic value of comprehensive extensive monitoring which influences and controls therapy by retrospective informations. PMID- 1896908 TI - [Pleural mesothelioma in data from the Surgical Clinic in Hradec Kralove 1971 1987]. AB - The authors describe a group of 12 patients operated at the Surgical Clinic in Hradec Kralove in 1971-1987 with the diagnosis of a pleural mesothelioma. This tumour was found most frequently in the 6th decade. A slight predominance of women was found. Risk factors which might be associated with the development of a mesothelioma were found only in one patient. This disease is often recorded in a too advanced stage as it is manifested by a late, poor and non-specific symptomatology. In the authors' group of patients operated on account of mesothelioma the tumour was removed in six patients. Only those survive where the mesothelioma had a benign localization 2 patients). The fate of one patient could not be traced. All patients with the histological classification of malignancy in the diffuse or localized form died (9 patients), even when the tumour was surgically removed (3 patients). This fact indicates the great aggressivity of malignant mesotheliomas. PMID- 1896909 TI - [Use of the tissue glue, Tissucol, in experimental liver injuries]. AB - The authors investigated in experiments on rabbits the course of recovery of liver injuries after treatment with the fibrin glue Tissucol, as compared with a control group of animals where the injured liver was not treated. Healing was followed-up at several time intervals. Rupture of the liver left to spontaneous healing was at first unsatisfactory from the histological aspect (wide demarcation margin near the necrosis). Subsequently the margin disappeared however. The scar was minimal after two months and were no manifestations of inflamed parenchyma surrounding the scar. When Tissucol was used, as a rule favourable healing was achieved. Scarring was satisfactory although the connective tissue was somewhat wrinkled and the scar was not linear. On the whole the tissue glue Tissucol is favourable in the final stage despite the fact that during healing a granulomatous reaction to the glue developed and the proliferation of the minor biliary pathways persisted also in the final stage of the experiment. PMID- 1896910 TI - [Ultrasonography as an aid in the detection of intestinal invagination]. AB - The authors demonstrate on two case-histories of intestinal invagination in children the effectiveness and aptness of ultrasonographic examination which contributes towards early diagnosis and therapy. They recommend this method therefore in case of obscure findings of the child abdomen as a routine examination. PMID- 1896911 TI - [Problems in colorectal carcinoma in type 2 hospitals]. AB - The authors discuss the problem of colorectal carcinoma, its diagnosis, treatment and subsequent follow-up of patients under conditions of type 2 hospitals. In the authors' opinion well equipped institutes at this level can provide all necessary care to patients with carcinoma of this type. They emphasize in particular postoperative care and the follow-up of patients for several years. PMID- 1896912 TI - [A case of acute intestinal hemorrhage in diverticulitis treated by myotomy]. AB - The authors describe the case of a male patient with massive enterorrhagia in divericular disease of the colon. After conservative treatment failed, the patient was successfully treated by Reilly's myotomy. PMID- 1896913 TI - [Long-term prognosis of patients after successful embolectomy in the upper mesenteric artery]. AB - The authors describe case-histories of two patients after successful embolectomy from the mesenteric artery, in one combined with resection of the small intestine with survival of 1 and 13 years resp. without sings of malnutrition. The authors discuss the prognosis of embolectomised patients with regard to the basic disease, relapsing embolization and nutritional disorders. PMID- 1896914 TI - [Fibrin tissue glue, its preparation and methods of application]. AB - Fibrin glues used abroad are not imported to this country. Experience assembled abroad confirms the great possibilities to use them in the treatment of various tissues in all surgical disciplines. Attempts to apply this method must start by the elaboration of a similar system of glues from local raw materials. The effectiveness depends on the quality and concentration of individual components. The authors present a report on the possibility to elaborate a tissue glue from local resources using fibrinogen obtained from homologous blood or the patient's own blood. Fibrinogen USOL, Antilysin Spofa, Trombin Imuna and Calcium chloratum Spofa are readily available. The authors mention methods of the most suitable dilution of fibrinogen and methods how to obtain concentrated fibrinogen from autologous blood. They describe the preparation of both constituents of the glue for application and different methods of application. They evaluate advantages of different methods of administration. The authors describe also their own experience with the preparation and use of fibrin glue and experience with his own system of application. The advantages of fibrin tissue glue were proved by its use in different areas of surgery. Its particular importance was described in the treatment of injuries of parenchymatous organs. PMID- 1896915 TI - [Hemostatic and adhesive properties of fibrin tissue glue in an experiment]. AB - The authors compared in experiments the adhesive properties and haemostatic action of the foreign preparation Tissucol with a gluing system elaborated from locally produced constituents. The lack of availability of foreign fibrin tissue glues leads to their inadequate use in our departments. Readily available local preparations can reduce this shortcoming. They are, however, not adequately used so far. The objective of the present work was to test the adhesive and haemostatic action of several gluing systems, which differ by their fibrinogen concentration. The gluing systems were created by a similar composition and concentration as Tissucol. Experiments were performed on 22 rabbits under general i.v. and i.m. anaesthesia. The adhesive properties were tested by the firmness of a glued skin autotransplant, the haemostatic action by gluing a bleeding piercing wound of the liver. The authors proved the effectiveness of all used fibrin systems which have different qualities. The properties of Tissucol were matched only by a glue with a high fibrinogen and thrombin concentration. Our presentations can reliably replace foreign fibrin glues. PMID- 1896916 TI - [Tissue glues and the fibrin glue system]. AB - The authors submit a report on the present state of development of tissue glues and their use in medicine. They characterize synthetic glues and the fibrin gluing system. They draw attention to the advantages and shortcomings of both systems. The composition of the fibrin glue is analyzed and its properties are analyzed, incl. the relation to treated tissue. Attention is drawn to the favourable properties of fibrin tissue glue in the treatment of tissues, the authors evaluate its sole use as well as its use in combination with traditional suture. They also mention preparations used in the production of the glue and compare the costs of their preparation. Principles for the production of the two components and prerequisites of their wider use in future are emphasized. PMID- 1896917 TI - [Liver resection]. AB - The authors present the experience of their department with resections of the liver. Their main attention is focused on indications and the technique of operation. During the period from 1981 to April 1990 at the Surgical Clinic in Brno 50 resections of the liver were made. Thirty patients with benign diseases were operated and 18 patients with malignant diseases. The group comprised only those resections where at least one liver segment was removed. In two patients re resection on account of a tumour relapse was performed. For arrest of haemorrhage from the resection area the authors recommend in addition to careful surgical treatment also the use of fibrin glue. PMID- 1896918 TI - [Is surgical treatment indicated in choledocholithiasis?]. AB - Surgical exploration of the biliary pathways on account of relapsing or forgotten concrements in the biliary pathways in patients above 70 years with associated diseases has a high morbidity and mortality. The authors present an account of a group of patients from their departments; these patients with choledocholithiasis were treated by the at present ever more frequently used method--endoscopic sphincteropapillotomy. In the discussion the authors deal with possibilities to use EPS in the treatment of choledocholithiasis with a cholecyst in situ, acute pancreatitis with biliary genesis but also acute cholangoitis with the background of choledocholithiasis. They consider EPS the therapeutic method of choice in choledocholithiasis and report very good immediate as well as long-term results. PMID- 1896919 TI - [Peroperative peritoneal lavage and intra-abdominal instillation of antibiotics in an experiment]. AB - The authors present the results of an experiment on dogs where lethal diffuse peritonitis was induced in the standard way and was treated only by peroperative peritoneal lavage during reoperation within 24 hours. In the first group (n = 10) this method alone reduced the mortality despite the adverse prognosis to 70%, after addition of an effective antibiotic and metronidazole into the last lot of the lavage solution in the second equally sized group to 10%. The results prove a marked therapeutic asset of this method which as part of comprehensive treatment of peritonitis improves substantially the final effect also under clinical conditions. PMID- 1896920 TI - [Blunt injuries of the abdomen with localized chylous ascites]. PMID- 1896921 TI - [Surgery of inguinal hernia using a modification of McVay's method]. AB - The authors demonstrate the procedure and results of a modified method of surgery of inguinal hernias. Mc Vay's method resolves, contrary to other methods used in this country, also problems of the posterior wall of the inguinal canal. The operation involves: 1. closure of the defect in the fascia transversalis, 2. relieving incision of the sheath of the m. rectus abdom., 3. dislocation of the outlet of the funiculus on the cranial side, 4. placement of the funiculus between the lamina of the aponeurosis of the m. obliquus abdom. The authors use this method for operation of inguinal hernias since 1971. They present a group of 455 patients operated during the last five years, incl. results. PMID- 1896922 TI - [Characteristics of the aged surgery patient]. AB - In 32 old people selected at random (16 men and 16 women) indicators of the water and mineral salt balance were investigated as well as renal and hepatic functions, nutritional status, serum insulin, thyroxine and triiodothyronine and in 12 also changes after operation. The findings indicate that it is necessary to ensure clinical and biochemical monitoring as well as proper preparation of old people for a planned surgical operation. Old people must be always considered critical patients and it is important to provide extra preoperative and postoperative care. PMID- 1896923 TI - Applications received in 1987 and allowance rates for supplemental security income. AB - Since the inception of the Supplemental Security Income (SSI) program in 1974, counts of the numbers of cases processed and individuals who were awarded SSI payments have been available. This study breaks new ground, however, by using administrative data to describe in greater detail the characteristics of persons who applied for SSI over a 1-year period. The information on allowance rates is unique because, for the first time, the data have been gathered from the same set of applications. This article tracks the application process to determine whether or not benefits were subsequently received by these SSI applicants in the ensuing 18 months. Of the 1.2 million persons who applied for SSI during the study period, a large proportion were disabled. Among persons whose application was based on age, a greater proportion applied when they attained age 65 than at any other age and they were the most likely to qualify for payments under the program. The data also show how many of the 1.2 million applicants had previously been SSI recipients. In addition to providing demographic and SSI data, the allowance rates are useful in predicting trends in the composition of the caseload. PMID- 1896924 TI - On salivary film formation and bacterial retention to solids. A methodological and experimental in vitro study. AB - A parallel-plate flow cell system was developed to assess individual and combined parameters relevant to oral microbial retention. In this system, internal reflection germanium prisms represented oral solid surfaces including tooth surfaces. The system used, allowed adsorbed protein films to be analyzed in situ by multiple non-destructive surface analytical techniques, without provoking surface associated biofilms. Using a range of biochemical and biophysical techniques, germanium prisms of medium critical surface tension were noted to accurately model film formation at tooth-saliva interfaces. A range of clinically relevant temperatures (22 and 37 degrees C), rinse shear rates (1 and 32 ml/min) and critical surface tensions (high, medium and low) were systematically tested in the flow-cell system for their influence, if any, on salivary microbial retention from whole human saliva. Comparisons of the interfacial organization of adsorbed material were made between human parotid (HPS) and submandibular sublingual (HSMSL) salivas. The influence of these salivary secretions was also tested on the retention capacities of Streptococcus sanguis and Streptococcus salivarius. Microbial retention was found to be significantly dependent on initial critical surface tensions and rinse flow rates, but not to be affected by tested temperatures. When compared to prisms of low and high critical surface tension, medium critical surface tension prisms retained the highest numbers of microorganisms. No statistically verified morphological selectivity was observed in the retained microbial populations. When the interfacial organizations of HPS and HSMSL were evaluated at low- and medium energy surfaces in the absence and presence the streptococci, comparatively thinner and denser films with pronounced bacterial retention was noted for HPS on prisms of low critical surface tension. In the presence of saliva or salivary fractions, no difference in retention capacities was observed between the tested bacterial strains. The data suggest that in the presence of saliva, physico-chemical and mechanical factors have a major influence on the short term microbial retention to solid surfaces. The amount of salivary proteins being initially retained to a material also seems to be more directly related to the critical surface tension quality of the solid than to the type of bacterial strain present in suspension. The empirical critical surface tension of a material is thus a useful predictor of both microbial retention capacities and primary interactions between saliva and solid surfaces. PMID- 1896925 TI - Panoramic radiography in the assessment of the marginal bone level. AB - The radiation dosage for the Orthopantomograph model OP5 was measured using two different sizes of collimators. The concordance between and accuracy of panoramic radiography and periapical and bitewing radiography was examined regarding assessment of the marginal bone level. The measurability of panoramic and periapical and bitewing radiographs was compared, as was the image quality of panoramic radiographs from one selected sample and two random samples. The energy imparted was 0.4-0.8 mJ for one panoramic radiograph. The use of the narrow collimator reduced the dosage by about one-third. The concordance between panoramic and intraoral radiography was high. In some anatomical regions, the concordance was as high as the intraobserver agreement for one and the same technique. The concordance was lower in sites with severe bone loss, however. Sounding was very accurate for the measurement of the marginal bone loss. Of the radiographic techniques, periapical radiography was most accurate. The observer performance for linear measurements of bone loss varied substantially and systematically among five observers. The measurability in the upper arch was the same in panoramic and periapical radiography. In the lower arch, the measurability of periapical radiography was better. The image quality of panoramic radiography influenced the measurability. The image quality of panoramic radiographs from random samples was inferior to that of the selected sample. It was concluded that, for the assessment of the marginal bone level, the panoramic radiograph should be the radiographic examination of choice, if increased image quality is achieved. PMID- 1896926 TI - Sorbitol transport and metabolism by oral streptococci. AB - Sorbitol transport by oral streptococci was mediated by a phosphoenolpyruvate phosphotransferase system (PTS). The transition of S. sanguis 160 from continuous growth on limiting glucose to limiting sorbitol resulted in induction of EIIsor of the sorbitol-PTS, as well as sorbitol-6-P dehydrogenase which converts sorbitol-6-P to fructose-6-P. Sorbitol transport activity required the presence of a soluble sorbitol-specific component of the PTS, tentatively identified as an enzyme III for sorbitol (IIIsor). In addition, the results indicated that sorbitol transport can be mediated by the ELLglc, particularly in the presence of the sorbitol-specific component. S. sanguis 160 utilized sorbitol in a manner different from that reported for S mutans. Growth on glucose by S. sanguis 160 was inhibited by the presence of sorbitol in the growth medium and sorbitol was utilized in the presence of glucose. In addition, pulses of glucose added to cultures growing on sorbitol resulted in expulsion of sorbitol from the cell. Sorbitol was shown to interfere with glucose metabolism by S. sanguis 160 by inhibiting glucose transport by sorbitol-limited cells, but not by glucose limited cells, and by inhibiting glycolytic activity with glucose as the substrate. Furthermore, sorbitol was an effective repressor of the glucose-PTS, exhibiting negative regulation over synthesis of both EIIglc and a soluble component of the glucose-PTS, presumably IIIglc. Oral streptococci metabolize sorbitol to large amounts of formate and ethanol in addition to smaller amounts of lactate and acetate. The metabolism of sorbitol by S. sanguis and S. gordonii was less sensitive to oxygen than that by S. mutans and S. mitis. PMID- 1896927 TI - Recent clinical alert supports benefits of carotid endarterectomy. PMID- 1896928 TI - TMA House of Delegates turns up heat on tobacco industry. PMID- 1896929 TI - Report allergic reactions to latex to FDA. PMID- 1896930 TI - Is there life after medicine? Texas physicians talk about retirement. PMID- 1896932 TI - Rural health coalition announces legislative priorities. PMID- 1896931 TI - UR reform, indemnification bills beat legislative deadline. PMID- 1896933 TI - Council members focus on surrogacy and self-testing. PMID- 1896934 TI - Volunteer liability. PMID- 1896935 TI - Clarification on blood donation and HIV testing. PMID- 1896936 TI - Curing rural health problems is simple: quit the discrimination! PMID- 1896937 TI - Call me 'doctor'. PMID- 1896939 TI - Simplifying the hassles. PMID- 1896938 TI - Physicians need to know ins and outs of state dollars. PMID- 1896940 TI - Discrimination against the disabled is a potential civil rights issue. PMID- 1896941 TI - More about physicians' obligation to indigent patients. PMID- 1896942 TI - Abuse of elders: a review for Texas physicians. AB - Abuse of elders is a widespread but largely invisible problem in the United States. This problem and its detection, management, and prevention are described. Specific attention is directed toward risk factors for abuse and toward suggestive signs and symptoms. Texas laws and the physician's responsibility for reporting and intervening in cases of elder abuse are discussed. Strategies for intervention and prevention are outlined. PMID- 1896944 TI - Electroacupuncture's role in the management of reflex sympathetic dystrophy. PMID- 1896943 TI - Reflex sympathetic dystrophy and electroacupuncture. AB - Reflex sympathetic dystrophy (RSD) is a painful and progressively debilitating condition. Untreated, it leads to changes in the patient's lifestyle that are consistent with chronic pain syndrome. This general overview of contributing factors, signs and symptoms, diagnosis, and treatment of RSD presents three consecutive cases for which electroacupuncture (EA) proved to be an effective treatment for RSD pain. Possible underlying neuroanatomical mechanisms of RSD are addressed and the scientific basis for EA is considered briefly. PMID- 1896945 TI - Physicians' management of health effects related to industrial exposures: two case reports. AB - Although physicians play a vital role in diagnosing and treating health effects related to industrial exposures, most physicians have limited training in occupational and environmental medicine. Two cases of industrial exposure, one affecting an individual and the other, a community, are described to illustrate the need for physicians' awareness of such exposure and their need to know how to manage potential health effects. Resources to assist in identifying and managing these exposures and their related conditions are discussed. PMID- 1896946 TI - Two chromosomes with multigene families. AB - Watterson's formulae for the distribution, mean, and variance of the number of alleles in common on two chromosomes with multigene families are derived as simpler forms, and extended to chromosomes with an infinite number of genes, each evolving as in an infinitely many alleles model. PMID- 1896947 TI - The effects of admixture and population subdivision on cytonuclear disequilibria. AB - We examine the generation of cytonuclear disequilibria by admixture and continued gene flow. General formulas analogous to the nuclear case are first derived showing that the allelic and genotypic disequilibria from admixture or population subdivision equal their expected value across the contributing (sub) populations plus the covariance across these sources between the cytoplasmic gene frequency and the relevant nuclear frequency. A detailed study is then presented of the cytonuclear dynamics, in a random-mating population under two different migration scenarios. In both cases closed-form solutions are given for all variables as a function of the initial conditions and relevant migration parameters. The dynamics of the gene frequencies and allelic disequilibria, which dominate each system, are the same as those involving two unlinked nuclear loci, while the dynamics of the genotypic disequilibria and cytonuclear frequencies have no nuclear counterpart. The continent-island formulation focuses on a population receiving continued immigration from a large source of constant composition. A major discovery is that cytonuclear disequilibria can transiently build up on the "island" to levels far exceeding those found at equilibrium. In contrast, the admixture formulation focuses on the dynamics within two populations undergoing continued intermigration. Although in this case all cytonuclear associations must ultimately decay to zero, long-term transient disequilibria can develop which are many times their initial admixture values. For both migration scenarios it is shown that the time of population censusing relative to migration and reproduction dramatically affects both the amount and pattern of the nonrandom associations produced. The empirical relevance of these models is discussed in light of nuclear-mitochondrial data from a hybrid zone between European and North American eels and from a zone of racial admixture in humans. PMID- 1896948 TI - Statistical models of the overdispersed molecular clock. AB - The most commonly used statistical model to describe the rate constancy of molecular evolution (molecular clock) is a simple Poisson process in which the variance of the number of amino acid or nucleotide substitutions in a particular gene should be equal to the mean and henceforth the dispersion index, the ratio of the variance to the mean, should be equal to one. Recent sequence data, however, have shown that the substitutional process in molecular evolution is often considerably overdispersed and have called into question the generality of using a simple Poisson process. Several efforts have been made to develop more realistic models of molecular evolution. In this paper, I will show that the spatial (site-specific) variation in the rate of molecular evolution is an improbable cause of the overdispersion and then review various statistical models which take the temporal variation into account. Although these models do not immediately specify what the mechanisms of molecular evolution might be, they do make qualitatively different predictions and give some insight into their inference. One way to distinguish them is suggested. In addition, effects of selected substitutions that presumably occur after a major change in a molecule are quasi-quantitatively examined. It is most likely that the overdispersion of molecular clock is due either to a major molecular reconfiguration (fluctuating neutral space) led by a series of subliminal neutral changes or to selected substitutions fine-tuning a molecule after a major molecular change. Although the latter possibility, of course, violates the simplest neutrality assumption, it would not impair the neutral theory as a whole. PMID- 1896949 TI - Recessive hereditary deafness, assortative mating, and persistence of a sign language. AB - We model the cultural transmission of sign language when there is one-locus genetic variation for deafness and hearing. Our premises are that the deaf are more motivated to learn sign language than the hearing, and that a vertically transmitted sign language, unlike recessive hereditary deafness, cannot "jump a generation." Conditions are obtained for persistence (i.e. protection from loss) of signers. These conditions are more easily satisfied the greater the fraction of the hearing who also learn sign language and as the frequency of the recessive gene for deafness increases. Persistence is also facilitated by assortative mating for deafness, but not by assortment for signing. With vertical transmission only, it is necessary that one signer parent be able to transmit sign language with greater than one-half the efficiency of two. Under the assumption that the hearing do not learn sign language, the following additional results are obtained. Persistence is more likely with dominant as opposed to recessive inheritance. When recessive hereditary and acquired deafness co-occur, increasing the frequency of the latter has opposite effects depending on the degree of assortment. Opportunities for the deaf to learn sign language outside the family seem not to affect the conditions for persistence. PMID- 1896950 TI - A study of the foundations of ethical decision making of clinical medical ethicists. AB - A study of clinical medical ethicists was conducted to determine the various philosophical positions they hold with respect to ethical decision making in medicine and their various positions' relationship to the subjective-objective controversy in value theory. The study consisted of analyzing and interpreting data gathered from questionnaires from 52 clinical medical ethicists at 28 major health care centers in the United States. The study revealed that most clinical medical ethicists tend to be objectivists in value theory, i.e., believe that value judgments are knowledge claims capable of being true or false and therefore expressions of moral requirements and normative imperatives emanating from an external value structure or moral order in the world. In addition, the study revealed that most clinical medical ethicists are consistent in the philosophical foundations of their ethical decision making, i.e., in decision making regarding values they tend not to hold beliefs which are incompatible with other beliefs they hold about values. PMID- 1896951 TI - Why philosophers should offer ethics consultations. AB - Considerable debate has occurred about the proper role of philosophers when offering ethics consultations. Some argue that only physicians or clinical experienced personnel should offer ethics consultations in the clinical setting. Others argue still further that philosophers are ill-equipped to offer such advice, since to do so rests on no social warrant, and violates the abstract and neutral nature of the discipline itself. I argue that philosophers not only can offer such consultations but ought to. To be a bystander when one's discipline does offer insights and methods of value discernment is pusillanimous. But this position requires a view of clinical medical ethics as one that arises out of the clinical practice of medicine, and not just from an application of general ethical principles to the practice of medicine. I conclude with some skills that trained philosophers can bring to the consultation service, and note that all consultations are in the form of recommendations that the patient, family, and physician are still free to accept or reject. Philosophers in the clinical setting do not make decisions. PMID- 1896952 TI - The clinical ethicist at the bedside. AB - In this paper we attempt to show how the goal of resolving moral problems in a patient's care can best be achieved by working at the bedside. We present and discuss three cases to illustrate the art and science of clinical ethics consultation. The sine qua non of the clinical ethics consultant is that he or she goes to the patient's bedside to obtain specific clinical and ethical information. Unlike ethics committees, which often depend on second hand information from a physician or nurse, clinical ethics consultants personally speak with and examine patients and review their laboratory data and medical records. The skills of the clinical ethics consultant include the ability to delineate and resolve ethical problems in a particular patient's case and to teach other health professionals to build their own frameworks for clinical ethical decision making. When the clinical situation requires it, clinical ethics consultants can and should assist primary physicians with case management. PMID- 1896953 TI - AIDS, myth, and ethics. AB - The present paper is a commentary on an article by Larry Churchill. Churchill has argued that the negative attitudes and adverse behavior we commonly encounter in connection with (suspected) AIDS patients may be understood in terms of a dualistic 'myth' inspiring a 'ritual' avoidance of 'dirt', of 'dirt' as something that does not belong to a 'clean' world order. The deep-seated mythical character of attitudes and behavior here makes them less accessible to the kind of rational argument commonly employed in ethics. Churchill also proposes a remedy for the (morally outrageous) dualistic mythical-ritual behavior he has focused - a remedy that may be overly intellectualistic. Three further comments are made: on the metaphorical meaning of 'myth', on a reductionist tendency in Churchill's 'deep' looking project, and on an ethically crucial ambiguity in the meaning of the other person's 'otherness'. These (mildly critical) comments do not, however, detract from a positive overall evaluation of Churchill's basic idea that we will understand more about adverse attitudes and behavior in connection with AIDS if we think in terms of 'myth', 'ritual', 'dirt', and 'cleanliness'. PMID- 1896954 TI - An integrative model of clinical-ethical decision making. AB - The purpose of this paper is to propose a model of clinical-ethical decision making which will assist the health care professional to arrive at an ethically defensible judgment. The model highlights the integration between ethics and decision making, whereby ethics as a systematic analytic tool bring to bear the positive aspects of the decision making process. The model is composed of three major elements. The ethical component, the decision making component and the contextual component. The latter incorporates the relational aspects between the provider and the patient and the organizational structure. The model suggests that in order to arrive at an ethically, justifiable sound decision one make reference to those three elements. PMID- 1896955 TI - Causality assessment in epidemiology. AB - Epidemiology relies upon a broad interpretation of determinism. This paper discusses analogies with the evolution of the concept of cause in physics, and analyzes the classical nine criteria proposed by Sir Austin Bradford Hill for causal assessment. Such criteria fall into the categories of enumerative induction, eliminative induction, deduction and analogy. All of these four categories are necessary for causal assessment and there is no natural hierarchy among them, although a 'deductive' analysis of the study design is preliminary to any assessment. PMID- 1896956 TI - Measuring the quality of life: why, how and what? AB - In this paper three questions concerning quality of life in medicine and health care are analysed and discussed: the motives for measuring the quality of life, the methods used in assessing it, and the definition of the concept. The purposes of the study are to find an ethically acceptable motive for measuring the quality of life; to identify the methodological advantages and disadvantages of the most prevalent current methods of measurement; and to present an approach towards measuring and defining the quality of life which evades the difficulties encountered and discussed. The analysis comprises measurements both in the clinical situation concerning individual patients and in research concerning whole populations. Three motives are found for evaluating the quality of human life: allocation of scarce medical resources, facilitating clinical decision making, and assisting patients towards autonomous decision making. It is argued that the third alternative is the only one which does not evoke ethical problems. As for the methods of evaluation, several prevalent alternatives are presented, ranging from scales of physical performance to more subtle psychological questionnaires. Clinical questionnaires are found to fail to provide a scientific foundation for universally measuring the quality of life. Finally, the question of definition is tackled. The classical distinction between need-based and want based theories of human happiness is presented and discussed. The view is introduced and defended that neither of these approaches can be universally preferred to the other. The difficulty with the need approach is that it denies the subjective aspects of human life; whereas the problem of the want approach is that it tends to ignore some of the objective realities of the human existence. In conclusion, it is argued that the choice of methods as well as definitions should be left to the competent patients themselves--who are entitled, if they so wish, to surrender the judgement to the medical personnel. Technical factors as well as the requirements of respect for autonomy and informed consent support this conclusion. PMID- 1896957 TI - Hydrogen peroxide is an intermediate in the platelet activation cascade triggered by collagen, but not by thrombin. AB - Human blood platelets produce oxidant species when stimulated by collagen and thrombin. The oxidative burst of platelets has been studied by cytofluorimetry taking advantage of the fluorogenic dye DCFH2-DA, which is taken up and deacetylated by platelets and then oxidized to the fluorescent derivative DCF. The oxidation of DCFH2 is induced by stimulation with collagen but not with thrombin and inhibited by external catalase. Catalase also inhibited the aggregation induced by collagen, but not that induced by thrombin. Aspirin and indomethacin inhibited the formation of the fluorochrome only when platelets were stimulated by thrombin. Externally added H2O2 increased the cytoplasmic calcium content as probed by the fluorescence of Indo-1. The present data suggest that collagen induces the production of H2O2, which in turn may stimulate the aggregation of platelets through a calcium mobilization. Instead the stimulation by thrombin does not require the intermediacy of H2O2. PMID- 1896958 TI - Specific quantification of heparin-dependent antibodies for the diagnosis of heparin-associated thrombocytopenia using an enzyme-linked immunosorbent assay. AB - In order to specifically detect heparin-dependent antibodies in patients with suspected heparin-associated thrombocytopenia (HAT), an adapted ELISA test was developed. Serum-platelet bindable IgG (SPb-IgG) were measured in the absence and in the presence of heparin in the sera from a/ 25 normal controls, 25 patients treated by heparin without thrombocytopenia, 29 thrombocytopenic patients not receiving heparin and b/ 12 patients with confirmed HAT. In the absence of heparin, the 12 HAT sera showed normal or elevated SPb-IgG levels (range = 10.4 36 Arbitrary Units or AU) as compared to healthy controls (8-17.1 AU). After coincubation of HAT sera with heparin (0.25, 0.50, 0.75, and 1 IU/ml), SPb-IgG levels were consistently elevated (range = 22.8-150 AU), and this increase in IgG binding (equal in mean to 200%) was always inhibited with 5 IU/ml of heparin. In contrast, a mean maximum increase in SPblgG levels of only 20% was registered in all control groups whatever the tested heparin concentration. Thus, this ELISA allows the specific diagnosis of HAT by demonstrating a serum IgG binding on platelets only in the presence of therapeutic concentrations of heparin. PMID- 1896959 TI - Comparative antithrombotic activities of the phosphodiesterase inhibitors pelrinone (AY-26,768), AY-31,390 and milrinone. AB - The phosphodiesterase (PDE) inhibitors AY-31,390, milrinone and pelrinone (AY 28,768) were analyzed in human platelet aggregatory systems and in a rabbit arteriovenous shunt model to delineate their activity. AY-31,390 showed a remarkably potent capacity to inhibit human antithrombotic platelet aggregation. AY-31,390 inhibited arachidonic acid, U46619, collagen, epinephrine (second phase) and adenosine diphosphate (second phase) induced platelet aggregation (PA) with IC50 values of 0.18, 0.21, 0.54, 0.43 and 0.20 microM, respectively. Milrinone, although less potent than AY-31,390, inhibited PA with IC50 values of 2.1, 2.0, 5.4, 3.7 and 4.1 microM and pelrinone's IC50 values were 2.8, 6.6, 13.3, 18.6 and 11.8 microM, respectively. Platelets which were incubated with AY 31,390, milrinone or pelrinone, washed with Hanks' balanced salt solution and then resuspended in platelet poor plasma, lost their inhibitory activity in collagen and arachidonic acid PA systems. These results suggested that AY-31,390, milrinone and pelrinone did not bind tightly to cAMP PDE. If human platelet-rich plasma was pretreated with adenosine deaminase, an enzyme that degrades adenosine, the inhibitory effect of milrinone and to a lesser extent pelrinone was reversed. AY-31,390 did not produce a loss of activity with adenosine deaminase in the arachidonic acid system and only a small loss in the collagen system. Adenosine did not appear to be a meaningful factor in AY-31,390's inhibitory activity. Pelrinone, milrinone to a greater extent, and AY-31,390 to the greatest extent were effective inhibitors of white thrombus formation in the in vivo rabbit arteriovenous shunt model. These PDE III inhibitors were potent deterrants of platelet aggregation and white thrombus formation; these agents would be expected to be efficacious therapeutic antithrombotics. PMID- 1896960 TI - Heparin cofactor II significance for the inhibition of thrombin at the injured vessel wall. AB - The thrombin inhibitory role of antithrombin III (ATIII) and heparin cofactor II (HCII) was studied in vitro using intact and injured rabbit aortae. When intact vessels were loaded with thrombin and then exposed to either heat defibrinogenated human plasma (HDHP) or ATIII the same degree of thrombin inhibition was achieved demonstrating that ATIII was the only plasma component involved in thrombin inhibition on the intact vessel wall. When the media of the vessel wall was loaded with thrombin and then exposed to ATIII or HCII a significantly higher thrombin activity remained on the surface than when it was exposed to defibrinogenated plasma. A mixture of ATIII and HCII resulted in a greater inhibition of thrombin than ATIII or HCII alone. It is concluded that, contrary to what happens on the endothelium, HCII and ATIII inhibit additively thrombin on the injured vessel wall. HCII thus plays an essential role for the inhibition of thrombin at the injured vessel wall. It is also concluded that an additional plasma component participates in thrombin inhibition on the media but its contribution is negligible as compared with ATIII or HCII. PMID- 1896961 TI - Increase in the cytosolic concentration of calcium in platelets of diabetics type II. AB - The intracellular concentration of calcium (Cai) was measured in platelets of healthy control subjects and diabetics type II. Cai was elevated in platelets of diabetics type II under basal conditions, after stimulation by collagen, in the presence and absence of calcium in the incubation medium. The increase in Cai after stimulation by collagen was inhibited by nitrendipine in both kinds of platelets, however Cai remained elevated in platelets of diabetics. Our data and findings of others may be understood as indications of disturbances in the handling of Cai in diabetes. PMID- 1896962 TI - Microparticle generation during in vitro platelet activation by anti-CD9 murine monoclonal antibodies. AB - We used flow cytometry and two anti-CD9 murine monoclonal antibodies (NNKY1-19, MALL13) to investigate the glycoprotein composition and the potential functions of microparticles (MP) released by platelets exposed to these antibodies in vitro. NNKY1-19 produced aggregation with characteristics similar to those noted in previous reports. The action of MALL13 on platelets in platelet-rich plasma (PRP), however, differs from that of other anti-CD9 antibodies. The normal fluctuation in the MALL13-induced change in optical density disappeared when complement was present. MALL13-induced effect for platelet in PRP was not inhibited by preincubation with monoclonal anti-GPIIb/IIIa antibody, but was inhibited in washed platelets (WP). Furthermore, following MALL13 stimulation in PRP platelets, the amount of buffer LDH markedly increased and electron microscopy findings showed vacuoles appearing inside the platelets. These results suggest that MALL13 has at least two effects on platelets that differ for PRP platelets and WP. The number of MP released was increased by the addition of anti CD9 antibodies. MP surfaces were found to be rich in CD9 protein. MALL13 stimulation lead to a significant increase in the binding of C1q and C3 to platelets and caused the production of MP to occur more rapidly than it did the exposure of fibrinogen binding sites in the presence of complement. The analysis of the relationship of MP to anti-CD9 monoclonal antibody may be useful in the investigation of the relationship between platelet function and coagulation regulation. PMID- 1896963 TI - Generation of procoagulant (thromboplastin) and plasminogen activator activities in peripheral blood monocytes after total hip replacement surgery. Effects of high doses of corticosteroids. AB - Development of thromboplastin (tpl) and plasminogen activator (PA) activity in monocytes and the effects of high doses of corticosteroids (HCD) on these activities were studied in patients undergoing a standardized surgical trauma. Twelve patients who received uncemented total hip prostheses were divided into a nonsteroid group (n = 6) and a steroid group (n = 6). We found no significant differences between the two patient groups regarding tpl or PA activities of peripheral blood mononuclear cells (PBM) isolated during the postoperative phase. However, in the nonsteroid group there was a tendency for increased expression of procoagulant activity and decreased fibrinolytic activity on the 1st postoperative day, favoring the formation of fibrin in the monocyte microenvironment. Further, PBM isolated on the 1st and 2nd day after surgery were significantly less capable of generating tpl activity on endotoxin stimulation than cells isolated preoperatively. This was not the case in the steroid group. These patients had also a tendency for decreased fibrinolysis at the end of the 1st postoperative week, indicating increased imbalance towards a more thrombotic stage after surgery. PMID- 1896964 TI - Preparation of monoclonal antibodies to the thrombin/hirudin complex. AB - Monoclonal antibodies (mAbs) binding to the thrombin/hirudin (T.H) complex were prepared by either immunizing mice with hirudin and by screening for the mAbs cross-reacting with the T.H complex (group I), or by immunizing the animals directly with the T.H complex (group II). Epitope mapping of the mAbs of group I indicated that all the mAbs were binding to the hirudin N-terminal core domain only (residues 1-43). Among the mAbs raised against the T.H complex (group II), one mAb recognized an antigenic determinant expressed selectively upon binding of hirudin to thrombin. A double antibody sandwich type ELISA combining the mAb of group II with a mAb of group I was developed, allowing the determination of the T.H complex in human citrated plasma down to nanogram concentration levels. PMID- 1896965 TI - Which factors affect high D-dimer levels in the elderly? AB - To study the age-related changes in plasma D-dimer levels and the effect of atherosclerotic disease and long-term immobilization on haemostasis the elderly, we measured plasma D-dimer levels in 148 subjects aged from 60 to 94 years using an ELISA. We also measured plasma fibrinogen, serum uric acid, total cholesterol, triglycerides, HDL cholesterol, beta-lipoprotein fractions, and apolipoproteins (A-I, A-II, B, E). Plasma D-dimer levels (326 +/- 148 ng/ml) were significantly higher in the healthy elderly subjects than in younger controls (180 +/- 58 ng/ml, p less than 0.01) and increased further with age (r = 0.344, p less than 0.01). D-dimer levels were significantly higher in elderly women than in elderly men (p less than 0.05). The D-dimer level correlated significantly with both the fibrinogen antigen level (r = 0.286, p less than 0.001) and the clotting activity (r = 0.275, p less than 0.01), and also correlated with apolipoprotein E levels. There were no correlations with the other parameters assessed. The D-dimer levels were significantly higher in the elderly subjects with atherosclerotic disease (516 +/- 285 ng/ml) than in healthy elderly subjects (p less than 0.001). Moreover, the levels were even higher in elderly subjects with long-term immobilization (866 +/- 408 ng/ml) than in subjects with atherosclerosis, even after age, sex and underlying diseases were taken into consideration. These results indicate that coagulation and fibrinolysis activity are increased in the elderly, especially those with atherosclerotic disease and that moreover long term immobilization further accelerates their haemostatic hyperactivity. PMID- 1896966 TI - Effect of thrombin on the production of glycosaminoglycans by cultured endothelial cells. AB - We investigated the effect of thrombin on the production process of glycosaminoglycans (GAG) in cultured bovine aortic endothelial cells. It was revealed that the trichloroacetic acid-insoluble [35S]sulfate-labeled GAG (35S GAG) was decreased by thrombin. The thrombin-induced decrease in the accumulation of 35S-GAG in the cell layer occurred even in the presence of actinomycin D or cycloheximide. The incorporation of both [35S]sulfate and [3H]glucosamine into the GAG was decreased by thrombin, while the ratio of 35S to 3H was not changed. Also, the incorporation of both [3H]glucosamine and [14C]UDP-xylose into the GAG was inhibited by thrombin. From these results, it was suggested that thrombin decreased GAG in the endothelial cell layer through an suppression of formation of polysaccharide chains rather than that of core protein. PMID- 1896967 TI - An assay system for the modulators of plasminogen activation on the cell surface. AB - Plasminogen activation on the cell surface is regulated by a variety of modulators which balance surface-bound plasminogen activators (PAs) and plasminogen activator inhibitors (PAIs). In this study, we developed as assay system to assess modulation of cell-associated plasminogen activation. Plasmin generation by endogenous plasminogen activators was measured with a combination of exogenously added plasminogen and a chromogenic substrate, S-2251, in the presence of living cells. A cell surface PA activity was quantitated by adopting a rate of plasmin generation. We used HT-1080, a human fibrosarcoma cell line, as representative of cells which have both PAs and PAIs on their cell surface. A basal level of cell surface PA activity was specifically reduced by anti urokinase-type PA IgG and enhanced by anti-PAI-1 IgG, suggesting that the basal level is determined by a balance between uPA and PAI-1 on the cell surface. We examined effects of dexamethasone and thrombin on cell surface PA activity in the assay system. Dexamethasone appeared to suppress the cell surface PA activity by enhancing de novo synthesis of PAI-1, whereas thrombin suppressed it by inactivating single-chain urokinase-type plasminogen activators. These results indicate that our assay system can be adapted for the screening of various types of PA modulators. PMID- 1896968 TI - Interaction of the sulfated lactobionic acid amide LW 10082 with thrombin and its endogenous inhibitors. AB - The synthetic polyanion LW 10082 prolonged thrombin clotting times when human or bovine thrombin were used to induce clotting. In the clotting time prolongation LW 10082 was 15 times more potent in the presence of human thrombin than of bovine thrombin. In an amidolytic thrombin inhibition assay, LW 10082 inhibited bovine and human thrombin when plasma was present. Here, too, thrombin inhibition was much more pronounced when human thrombin was used. When purified antithrombin III was used, neither human nor bovine thrombin were inhibited by LW 10082. LW 10082 proved to be a potent inhibitor of human thrombin in the presence of heparin cofactor II in an amidolytic assay. The time course of the inhibition was slow and at least 10 minutes of incubation were required to obtain complete inhibition of thrombin by an excess of HC II and LW 10082. The anticoagulant activity of LW 10082 in the APTT was unchanged in the presence of anti antithrombin III antibodies while the potency of heparin was clearly reduced. This indicates that the overall anticoagulant effect of LW 10082 was as well independent of antithrombin III. PMID- 1896969 TI - In vitro and in vivo effects of a peptide mimetic (SC-47643) of RGD as an antiplatelet and antithrombotic agent. AB - Platelet aggregation requires binding of fibrinogen (fgn) to activated platelets and inhibition of this binding blocks platelet aggregation. Synthetic peptides modeled after the platelet binding sequence on fgn block the platelet glycoprotein IIb/IIIa receptor and effectively inhibit aggregation. SC-47643 (SC) is a mimetic of the RGD-containing peptide sequence that is recognized by the platelet IIb/IIIa receptor. SC inhibited fgn binding to activated platelets (IC50: 1.0 x 10(-5) M) and prevented platelet aggregation in response to a variety of platelet agonists in both washed human platelets and platelet rich plasma (IC50's ranging from 4 x 10(-6) to 1 x 10(-5) M, respectively). SC inhibited collagen induced thrombocytopenia in the rat (ED50 0.07 mg/kg and t1/2 36 min). In dogs ex vivo collagen induced platelet aggregation was inhibited 50% after a bolus injection of 1.7 mg/kg. After a steady state infusion (2 hr), the ED50 was 0.03 mg/kg/min, with no effects on blood pressure, heart rate or platelet count. These data demonstrate that SC, a peptide mimetic of the natural fgn binding sequence, is capable of blocking platelet-fgn interactions and platelet aggregation. PMID- 1896970 TI - An "in vitro" quantitative assay for drugs that stimulate prostaglandin release. PMID- 1896971 TI - Heparin released platelet factor 4 in uncomplicated type 1 diabetes mellitus. PMID- 1896972 TI - [Mercury in medicine and dentistry. Historical reflection]. PMID- 1896973 TI - [Rational use of laboratories. How to assure the quality of analyses]. PMID- 1896974 TI - [How dangerous are benzodiazepines?]. PMID- 1896976 TI - [C-reactive protein, SR and white blood cell count in acute lower respiratory tract diseases. The usefulness of blood tests in diagnosis of pneumonia]. AB - C-reactive protein (CRP) analysis, erythrocyte sedimentation rate and white blood cell count were evaluated as tests in the diagnosis of pneumonia in 84 patients with acute lower respiratory disease. Marked elevated values of CRP were frequently found in pneumonia patients, whereas in most patients with acute asthma, acute exacerbation of chronic obstructive bronchitis and acute bronchitis the values were within the normal range. The combined sensitivities and specificities of the tests were best for CRP, followed by erythrocyte sedimentation rate and white blood cell count. PMID- 1896975 TI - [Benzodiazepines--attitudes and prescription practice among general practitioners and psychiatrists]. AB - 64 general practitioners and 42 psychiatrists in central Norway answered a questionnaire which evaluated the doctors attitudes to benzodiazepines through their responses to 19 statements regarding these drugs. In addition, eight patient questionnaires were used to assess prescribing habits regarding benzodiazepines. There was considerable variation between the responses from the two groups of doctors. Psychiatrists exhibited significantly (p less than 0.001) more negative attitudes and stricter prescription habits as regards benzodiazepines than general practitioners did. Another finding was a significant and positive correlation between attitudes and prescribing habits. PMID- 1896977 TI - [Carotid endarterectomy. Surgical complications and long-term prognosis]. AB - 227 patients underwent 259 carotid endarterectomies because of transitory ischemic attacks (TIA). All had a 50% or more carotid lumen reduction as revealed by angiography, and symptoms from the arteriosclerotic lesion. Surgical mortality/morbidity at 30 days was 2.6%. 5.3 years after the operation (1 month 13 years) the probability of stroke was 4.9%, which corresponds to a postendarerectomy stroke rate of 1% per year. The procedure may be of value if the rate of surgical complication is very low, but the net effect still depends upon the occurrence of other vascular complications during the follow-up period. The incidence of vascular diseases in this series of seriously affected arteriosclerotics was higher than in a matched normal population, and mortality was much higher. At present a somewhat restrictive indication for surgery seems justified. PMID- 1896978 TI - [Causes of death among mentally retarded. Naerlandheimen Central Institution for the Mentally Retarded]. AB - At Naerlandheimen Central Institution for mentally retarded a retrospective enquiry was conducted into causes of death. The enquiry included 186 deaths during the period from 1948 to January 1, 1990. The average age of deceased persons was 37.9 years. In approximately 40% of the cases infections were stated as the cause of death. All in all 32.5% of deaths were due to infections of the respiratory system, and diseases of the central nervous system constituted 8.9%. Cancer and coronary heart diseases, which dominate the statistics of causes of death in the average population, constituted respectively only 2.4% and 4.1% of the deaths. PMID- 1896979 TI - [Psychiatry for the elderly--a specialty field in progress]. AB - Services concerned specially with elderly people who are mentally ill have developed in response to changing needs and expectations in society. In Norway, more than 600 beds in psychiatric hospitals are allocated to geriatric psychiatry (gerontopsychiatry), and are served by 20 senior registars and 19 psychiatric trainees. There are hardly any outreach programmes. Most of the beds in the hospitals are occupied by long-term psychiatric patients. There is little consensus as to what type of patients these beds should primarily serve. The authors recommend that a special unit to deal with geriatric psychiatry be organized in every county in Norway. Funds should also be allocated for professorships in this field. PMID- 1896981 TI - [Diagnosis of Spielmayer-Vogt disease. Electron microscopy of conjunctival biopsy]. AB - The authors describe ultrastructural changes in conjunctival specimens from five patients with Spielmeyer-Vogt-Batten's disease. Four of the specimens contained lysosomal "fingerprint-bodies", regarded as a specific lesion for this disease. When the biochemical defect remains unknown, the recognition of these ultrastructural changes is a valuable diagnostic tool to supplement clinical and electrophysiological examinations. PMID- 1896980 TI - [Pelvimetry]. AB - It has been shown that, in all the different ways of performing pelvimetry, use of computed tomographic techniques leads to a significant reduction in radiation doses. We describe a new method of pelvimetry, involving computed tomography consisting of two scoutviews. The results of this method are compared with the results of conventional technique ad modum Fernstrom, measured in 55 women. Both methods showed large inter-observator differences. No statistically significant differences between the methods were revealed but the anteroposterior outlet was slightly smaller with the CT-technique (mean 6 mm). The method is recommended, since it is easy to use, and the rate of ionizing radiation is low. PMID- 1896983 TI - [Can the use of hypnotics be reduced? Systematic influence on attitudes and prescription practice in a psychiatric department]. AB - Because of frequent use of hypnotics to treat insomnia in the population in general and in institutions especially, an alternative programme of treatment has been developed at the psychiatric hospital, Modum Bads Nervesanatorium. The programme includes different components and levels of treatment, wherein use of hypnotics is the last choice. The main focus is on sleep hygiene, which consists mainly of working on the patients' own attitude towards and experience of sleep problems. The pre-requisite for running such a programme is a systematic approach to these attitudes among the staff, and the prescribing patterns by physicians. PMID- 1896982 TI - [Laboratory diagnosis of multiple sclerosis]. AB - In 26 patients with multiple sclerosis 100% responded abnormally to magnetic resonance imaging of the brain. Lesions in the posterior fossa were observed in 18 patients. The auditory brain stem response was abnormal in 15 patients, and 22 had abnormal immunoglobulins in the cerebrospinal fluid. The correlation between abnormalities of the auditory brain stem response and the magnetic resonance images was greatest in a subgroup where the two investigations were performed within a ten day interval. Results from magnetic resonance imaging, evoked potentials and cerebrospinal fluid investigations were used to reclassify 13 of 15 patients with clinically "possible" or "probable" multiple sclerosis to a higher level using Poser's criteria. Evoked potentials (the auditory brain stem response in particular) correlated best with clinical multiple sclerosis category. We recommend that magnetic resonance imaging is established as a first hand investigation in evaluations of multiple sclerosis. Evoked potentials and cerebrospinal fluid investigations may prove to be more specific, however, and these investigations should also be performed as a routine. PMID- 1896984 TI - [Subarachnoid hemorrhage. Treatment with nimodipine--a new calcium antagonist of dihydropyridine type]. PMID- 1896985 TI - [Rational use of tranexamic acid]. PMID- 1896986 TI - [Therapeutic principles in hyperkalemia]. PMID- 1896987 TI - [Aztreonam. A small-spectrum antibiotic in gram-negative infections]. PMID- 1896988 TI - [Specimen taking and transport for virologic diagnosis]. PMID- 1896989 TI - [Ambulatory non-invasive 24-hour blood pressure measurement--do we need it?]. AB - The introduction of non-invasive, portable, automatic blood pressure measurement devices enables characterization of the blood pressure profile throughout the day in an ambulatory setting. The article advises against uncritical use. 24-hour ambulatory blood pressure measurements have become a valuable tool in scientific research, however, especially in studies dealing with antihypertensive efficacy. In hypertensive patients with "white coat hypertension", important data cannot be obtained without the use of 24-hour ambulatory blood pressure monitoring or blood pressure measurement at home. PMID- 1896990 TI - [Physicians' work load. A comparison between company physicians and general practitioners in private practice]. AB - The authors describe and compare the work load of 26 general practitioners and 17 company doctors. All of them worked full time. The information was collected by means of a structured telephone interview. The results indicate a higher work load among general practitioners than among company doctors. Despite this, the general practitioners plan to remain working longer than the company doctors do. In both groups of doctors there were some who believed they risked developing the "burn-out syndrome". This problem was found among the youngest doctors, female doctors and doctors with a large number of consultations daily. PMID- 1896991 TI - [Do anti-smoking campaigns use a correct strategy?]. PMID- 1896992 TI - [Can breast cancer be prevented? Alcohol drinking as a preventive factor]. PMID- 1896993 TI - [The vaccine against meningococcal B disease]. PMID- 1896994 TI - [Searching literature at MIC (Medical Information Center). Experiences from primary health services at a distant municipality]. PMID- 1896995 TI - [The curse of the computer tomograph]. PMID- 1896996 TI - In vitro metabolism and toxicity assessment of N-methylcarbazole in primary cultured rat hepatocytes. AB - N-Methycarbazole (NMC), a carcinogen and mutagen in tobacco smoke, was converted to two major metabolites by primary cultured rat hepatocytes as measured by high performance liquid chromatography (HPLC): N-hydroxymethylcarbazole (NHMC) and carbazole. These two metabolites had comparable retention times and identical ultraviolet spectra as those of reference standards. Identical retention times and mass spectra were also observed as detected by gas chromatography-mass spectroscopy (GC-MS) for NHMC and its reference standard. The toxicities of NMC and its two metabolites were assessed by lactate dehydrogenase (LDH) leakage and neutral red (NR) uptake. The rank order of cytotoxicity of NMC and its metabolites was found to be: NHMC greater than NMC greater than carbazole. Thus, we conclude that the hydroxylation of NMC to NHMC may represent a toxification step, while the further dealkylation to carbazole is most likely a detoxication process. PMID- 1896998 TI - Effect of lead on the glycosaminoglycans metabolism of bovine aortic endothelial cells in culture. AB - We investigated the effect of lead nitrate (0.1, 1.0, 10 or 20 microM) on the metabolism of glycosaminoglycans (GAG) in confluent cultures of bovine aortic endothelial cells. It was found that lead at 10 and 20 microM significantly decreased the accumulation of [35S]sulfate-labeled GAG ([35S]GAG) both in the cell layer and the medium after a 24-h culture. A time course study showed that 10 microM lead decreased the accumulation of [3H]glucosamine-labeled GAG both in the cell layer and the medium after 24 h and longer. The release of [35S]GAG from the cell layer during the last 3 h of a 24 h culture was not changed by lead. The detachment of [3H]thymidine-labeled cells from the monolayer was unaffected by lead. It was shown that lead at 10 microM decreased both heparan sulfate and the other GAG in the cell layer; the former was more sensitive to lead treatment. Lead at 20 microM and below failed to increase the release of lactate dehydrogenase, suggesting that non-specific cell damage was not caused by lead. From these results, it was suggested that lead decreases endothelial cell heparan sulfate content through a decrease in the GAG production without a non-specific cell damage. Lead may be a risk factor of vascular disorders. PMID- 1896997 TI - Relative effectiveness of some compounds for the control of cisplatin-induced nephrotoxicity. AB - Several procedures which have been reported as effective for the control of cisplatin induced nephrotoxicity were compared in the Sprague-Dawley rat using the same dose of cisplatin. The treatments examined were based on the use of sodium thiosulfate, sodium diethyldithiocarbamate (DDTC), glutathione (GSH), sodium N-methyl-D-glucamine dithiocarbamate (NaG) and S-2-(3 aminopropylamino)ethylphosphorothioic acid (WR-2721). The differences in the effectiveness of the procedures were assessed using BUN and serum creatinine values, histopathological examination, body weight changes, and renal platinum levels as indices. The effect of such treatments on the antineoplastic activity of cisplatin were examined with both the Walker 256 carcinosarcoma in the rat and the L1210 murine leukemia in mice. Under the conditions used, GSH was found to be more effective than the other nucleophiles in protecting against the nephrotoxicity of cisplatin while providing the least amount of interference with the antitumor activity as measured against the Walker 256 carcinosarcoma and the L1210 murine leukemia. Simultaneous i.v. administration of cisplatin and any of the sulfur-containing nucleophiles leads to a significant protection against the nephrotoxicity but reduced the anti-neoplastic activity of cisplatin when measured against the Walker 256 carcinosarcoma. PMID- 1896999 TI - Short-term effects of the tumor promoting polychlorinated biphenyl mixture, Aroclor 1254, on I-compounds in liver, kidney and lung DNA of male Sprague-Dawley rats. AB - The effects of a tumor promoting polychlorinated biphenyl mixture, Aroclor 1254, on I-compounds (tissue, species and sex dependent DNA modifications that increase with age in untreated rodents) were studied by 32P-postlabeling in male Sprague Dawley rat liver, kidney, and lung DNA. Aroclor 1254 was dissolved in corn oil and intraperitoneally (i.p.) injected (2 x 500 mg/kg, 2 weeks apart) into 3-month old rats. Control rats were given corn oil. Groups of 3 animals were sacrificed at 2 and 6 weeks after the second injection of corn oil or Aroclor 1254. At both time points Aroclor 1254-treated rats had significantly lower body weights and higher liver weights while kidney and lung weights were unaffected. Thymidine incorporation into liver and lung DNA was significantly increased at both time points, while kidney DNA showed a small decrease at 2 weeks. Treatment resulted in significant reductions (ranging from 29 to 100%) of each of nine liver I-spots at 2 and 6 weeks. In treated rats there was no decrease in kidney I-spots at 2 weeks, while the levels of only two out of ten kidney spots were reduced by 42 91% at 6 weeks. At 2 weeks three out of seven and at 6 weeks four out of seven lung I-spots were lowered by 51-100% in the Aroclor 1254-treated rats. Thus the effects decreased in the order liver greater than lung greater than kidney. Since Aroclor 1254 has been reported to be a tumor promoter in liver and lung but not kidney, these results suggest a correlation between organ specific promotion of carcinogenesis by Aroclor 1254 and the reduction of DNA I-compounds. PMID- 1897000 TI - Disposition and metabolism of [14C]1,2-dichloropropane following oral and inhalation exposure in Fischer 344 rats. AB - The objective of this study was to compare the disposition and metabolism of [14C]1,2-dichloropropane [( 14C]DCP) following oral and inhalation exposure since these two routes are of interest with regards to occupational and accidental exposure. [14C]DCP was administered orally to groups of four rats of each sex as a single dose of 1 or 100 mg/kg and as a multiple 1 mg/kg nonradiolabeled dose for 7 days followed by a single 1 mg [14C]DCP/kg dose on day 8. In addition, four rats of each sex were exposed to [14C]DCP vapors for a 6-h period in a head-only inhalation chamber at target concentrations of 5, 50 and 100 ppm. [14C]DCP was readily absorbed, metabolized and excreted after oral or inhalation exposure. For all treatment groups the principal routes of elimination were via the urine (37 65%) and expired air (18-40%). The tissues, carcass, feces and cage wash contained less than 11, 9.7 and 3.8% of the dose, respectively. The major urinary metabolites, as a group, from the oral and inhalation exposures were identified as three N-acetylcysteine conjugates of DCP, N-acetyl-S-(2-hydroxypropyl)-L cysteine, N-acetyl-S-(2-oxopropyl)-L-cysteine and N-acetyl-S-(1-carboxyethyl)-L cysteine. The majority (61-87%) of the expired volatile organic material was found to be parent DCP in all samples analyzed. Increasing the dose/concentration of [14C]DCP resulted in an increase in the amount of exhaled [14C]-volatile organics. The peak DCP blood concentrations (inhalation exposure) were not proportional to dose, indicating a dose-dependency in the blood clearance of DCP. Nonetheless, upon termination of exposure, DCP was rapidly eliminated from the blood. In all treatment groups, following oral and inhalation exposure the majority of the radioactivity was eliminated by 24 h postdosing and no differences were noted between sexes. Therefore, it can be concluded that in the rat the pharmacokinetics and metabolism of [14C]DCP are similar regardless of route of exposure or sex. PMID- 1897001 TI - Effect of allyl alcohol on xanthine dehydrogenase activity in the perfused rat liver. AB - Xanthine oxidase has been implicated in the production of reactive oxygen species and cell injury produced by various toxic compounds. Since allyl alcohol injuries the liver by an oxygen-dependent mechanism, we examined the actions of this hepatotoxicant on the conversion of xanthine dehydrogenase into xanthine oxidase in perfused livers. A microassay for NAD(+)-dependent xanthine dehydrogenase, based on measuring the production of NADH fluorometrically under anaerobic conditions, was developed and used to examine the actions of allyl alcohol on this activity in periportal and pericentral regions of the liver lobule. The oxygen-dependent activity, xanthine oxidase, was monitored in whole liver homogenates by uric acid formation at 302 nm under aerobic conditions. Perfusion of the liver with allyl alcohol (350 microM) increased xanthine oxidase and decreased xanthine dehydrogenase in whole liver consistent with the hypothesis that allyl alcohol enhanced calcium-dependent proteolytic conversion of the NAD(+)-dependent to the O2-dependent form. Xanthine dehydrogenase was higher in pericentral than in periportal regions of the liver lobule and tended to decrease selectively in periportal zones of livers exposed to allyl alcohol. O2 uptake was stimulated transiently by allyl alcohol followed by subsequent inhibition of respiration. These results are consistent with the idea that conversion of NAD(+) dependent xanthine dehydrogenase to xanthine oxidase is involved in the zone specific hepatotoxicity of allyl alcohol. PMID- 1897002 TI - Effect of ethanol on the disposition of paraquat. AB - Rabbits that received paraquat (200 mg/kg) and ethanol (1.0-3.8 g/kg) by gavage resulted in shorter median survival times and higher mortality rates than those dosed with paraquat alone. Plasma paraquat levels in rabbits dosed with ethanol before, after and concurrently with ingestion of paraquat were significantly higher when compared with animals without ethanol intake. Furthermore, substantial differences in paraquat kinetics, higher AUC, lower total clearance (CL/F) and volume of distribution (V/F) were seen in the ethanol-paraquat group. The effect of ethanol on acute paraquat toxicity is, at least in part, associated with the increase in paraquat absorption and/or the decrease in paraquat excretion. PMID- 1897003 TI - Disruption of the potential across the synaptosomal plasma membrane and mitochondria by neurotoxic agents. AB - The effect of a neurotoxic organo-metal, methyl mercuric iodide, and an aromatic solvent, toluene, upon the transmembrane potential (psi), across both the limiting membrane of isolated nerve terminals and their mitochondria, has been studied. Exposure of nerve endings to either of these toxicants in vitro resulted in a dose-dependent diminution of psi that was especially pronounced in the case of mitochondria. This was not prevented by a concurrent exposure to an antioxidant (alpha-tocopherol), or an iron chelator (deferoxamine), or ganglioside GM1. No significant changes were detected in synaptosomal potentials derived from cortices of rats exposed to methyl mercury or toluene at levels known to increase the rate of formation of reactive oxygen species within this region. The special vulnerability of mitochondrial psi to these agents may be due to the disruption of oxidative phosphorylation and may be related to the increase in intrasynaptosomal free ionic calcium that both of these chemicals can induce. PMID- 1897004 TI - The proconvulsive activity of quinolone antibiotics in an animal model. AB - The side-effect profile of quinolone antibiotics in man includes CNS disturbances such as dizziness, insomnia and convulsions. Although it has been suggested that the proconvulsive liability of quinolones involves an interaction with GABA receptors in the central nervous system, no animal model has been described to evaluate or confirm the mechanism of this effect. The proconvulsive activity of the quinolone antibiotics, nalidixic (NAL) and oxolinic (OXO) acid were tested in male mice following oral doses of 10-100 mg/kg utilizing the convulsive stimuli pentylenetetrazole (PTZ), picrotoxin, strychnine or electroshock. While NAL and OXO did not alter the threshold for convulsions induced by PTZ, strychnine or picrotoxin, both agents lowered the threshold for electroshock-induced seizures. Furthermore, the proconvulsive actions of NAL and OXO were completely blocked by the excitatory amino acid receptor antagonists, MK-801 and 2-amino-4 phosphonobutyric acid (AP-4). These data indicate that the mechanism of convulsive liability of quinolone antibiotics does not involve GABA receptor interactions as previously thought, but appears to involve activation of excitatory amino acid (EAA) receptors, possibly located in the optic region of the central nervous system. PMID- 1897005 TI - Lack of release from hepatocytes in vitro or excretion in vivo of mutagenic chrysoidine metabolites. AB - Rat liver postmitochondrial supernatant (S9) converted the azo dyes chrysoidine Y and R to products that were mutagenic towards Salmonella typhimurium strain TA100. No such release of mutagens was demonstrated using intact rat hepatocytes as an activation system despite the fact that chrysoidine dyes cause unscheduled DNA synthesis in these cells. It appears that genotoxic products produced within hepatocytes either react within the cell or are detoxified prior to release. Following intraperitoneal administration of chrysoidine Y to rats (100 mg/kg i.p.) there was also no evidence of mutagenic or por-mutagenic products excreted in bile or urine. The S9-derived mutagens appear to be largely independent of bacterial acetylation since they were active in the acetylation-deficient strain TA98/1,8-DNP6 in addition to strain TA98. The ultimate mutagenic form(s) are therefore unlikely to be acetoxyarylamines. PMID- 1897006 TI - Potentiation of diabetic glomerulopathy in uninephrectomized rats subchronically exposed to cadmium. AB - The renal effects of diabetes mellitus and cadmium (Cd), separately or in combination, were investigated in unilaterally nephrectomized female Sprague Dawley rats. Diabetes was induced by injection of streptozotocin and Cd was administered in drinking water at a concentration of 100 p.p.m. for 2.5 months. Cd did not affect the reduction in glomerular filtration rate or the rise in beta 2-microglobulinuria caused by diabetes. By contrast, the effect of diabetes on the urinary excretion of albumin, transferrin or IgG was greatly enhanced by concomitant exposure to Cd. This interaction occurred at Cd levels in the renal cortex which are very similar to those found in the general population of industrialized countries. These observations, in agreement with the results of a recent epidemiological study, suggest that Cd polluting the environment might potentiate the development of diabetic nephropathy. PMID- 1897007 TI - The effect of extraction solvent on the mutagenicity of airborne particles. AB - Two different solvents (acetone and dichloromethane) were compared for their efficacy in extraction of mutagenic compounds from airborne particulate samples. Their mutagenicity was examined with Salmonella typhimurium TA98 in presence or absence of S9 mix. The total mutagenic activity of the acetone extract was 1.8 7.0-fold that of the dichloromethane extract. The content of 1-nitropyrene, 1,6 dinitropyrene, dibenzo[a,h]anthracene and indo[1,2,3-c,d]pyrene in acetone extracts of airborne particulate samples was 3.8-, 3.6-, 6.6- and 1135-fold that of dichloromethane extracts, respectively. 1,8-Dinitropyrene, benzo[a]pyrene, chrysene, benzo[a]fluoranthene, benzo [a] anthracene, and benzo[g,h,i]perylene were found in the acetone extract, but were negative in the dichloromethane extract under the same conditions. However, the amount of pyrene in the dichloromethane extract was much higher than in the acetone extract. These results indicate that the extraction efficacy of 1-nitropyrene, dinitropyrenes and benzo[a]pyrene is higher with acetone than with dichloromethane. This may be the reason why acetone is the most effective solvent in extraction of mutagens from airborne particulate samples. PMID- 1897008 TI - Induction of graft-versus-host disease and rejection by sensitized small bowel allografts. AB - This study was undertaken to investigate under which circumstances graft versus host disease occurs following fully allogenic small bowel transplantation in the rat. To facilitate the development of GVHD, Brown-Norway donors were specifically sensitized against the Lewis hosts prior to transplantation. Additionally, the Lewis recipients were immunocompromised before transplantation using splenectomy, cyclosporine, and antilymphocyte serum. No further immunosuppressive therapy was administered after transplantation. When all pretreatment regimens were used, acute lethal GVHD arose in two of nine animals (22%), whereas in two animals (22%) signs of acute GVHD and rejection were observed concurrently. When recipients of sensitized grafts were pretreated with CsA alone, one of eight animals (12.5%) showed signs of GVHD and rejection. All other animals died of acute rejection without clinical signs of acute GVHD. However, histological signs of GVHD were observed frequently in hosts grafted with a sensitized small bowel transplant. These data show that acute lethal GVHD can occur when an immunocompromised host is grafted with a sensitized intestinal transplant. PMID- 1897009 TI - Evidence that residual host cells surviving the conditioning regimen to allogeneic bone marrow transplantation inhibit donor hematopoiesis in vitro--the role of TNF-alpha. AB - Blood cells were obtained from patients selected for allogeneic bone marrow transplantation who had undergone a conditioning regimen (CR) with high-dose chemotherapy and total body irradiation. The majority of residual cells bore CD3 antigen (range: 68-98%), and the CD4/CD8 ratio was normal. The effect of these residual/radioresistant cells on donor bone marrow hematopoiesis was investigated in eleven cases. Growth of donor CFU-GM and BFU-E was inhibited by 22-65% and 29 77%, respectively, when donor marrow was cocultured with residual cells at various ratios. In contrast, blood cells obtained from two patients prior to CR had no inhibitory effect. Supernatants obtained following incubation of residual cells from 9 patients were able to inhibit the growth of CFU-GM and BFU-E from normal unrelated subjects, whereas supernatants obtained before CR and from cultured normal marrow had no inhibitory effect. In addition, in blocking experiments, an anti-TNF-alpha MoAb was able to prevent this inhibition. Thus, TBI might be able to select and/or activate cells responsible for hematopoietic growth inhibition by a mechanism involving, at least in part, TNF-alpha. PMID- 1897010 TI - Effect of cold preservation on lymphocyte adherence in the perfused rat liver. AB - A study was designed to determine if cold preservation induces an increase in lymphocyte adherence to liver sinusoids on reperfusion. Rat livers were stored at 1 degree C in University of Wisconsin solution for 45 min, 8 hr, or 30 hr, and then reperfused for 90 min at 37 degrees C in an isolated perfused rat liver apparatus. Just prior to reperfusion, isogeneic rat lymphocytes prepared on a Ficoll-Paque gradient were added to the perfusate. In some studies lymphocytes were labeled with a fluorescent lipophilic membrane marker. There was no change in the number of circulating lymphocytes in an anhepatic circuit. When livers were present in the circuit, lymphocytes were lost from the perfusate into the liver in all studies, with the most rapid decrease occurring within 10 min of reperfusion. The length of preservation had a marked and statistically significant effect on the rate of disappearance of lymphocytes from the perfusate. Reduction by 50% of the number of lymphocytes infused did not affect the results when expressed as percent lymphocytes remaining in perfusate. To exclude the possibility that the loss of lymphocytes into the liver was due to a damaged subpopulation of lymphocytes, two livers stored 3 for 45 min were put into the circuit in sequence. The percent reduction in cells due to exposure to a second liver was not significantly different from that observed when cells were exposed only to a single liver. Histological studies showed fluorescence-labeled lymphocytes adherent in sinusoids, and the number of labeled cells was directly related to the length of preservation. Cold preservation induces an increase in lymphocyte adherence in the reperfused liver, which might be important in graft malfunction and rejection. PMID- 1897012 TI - Impairment of grafts by short-term warm ischemia in rat liver transplantation. AB - The mechanism of warm ischemic damage was investigated by assessing hepatic energy metabolism, mitochondrial functions, and lipid peroxidation (LP) of transplanted liver grafts in rats. Donor livers were stored ischemically either for 90 min at 4 degrees C (control) or for 20 min at 37 degrees C and 70 min at 4 degrees C (warm ischemia). In the control group, adenosine 5'-triphosphate (ATP) recovered within 8 min to 86% of the normal preischemic value (10.30, SEM 0.26 mumol/g dw). Total adenine nucleotides (TAN) recovered to 14.83 (SEM 0.22) mumol/g dw within 30 min, as compared with a normal level of 15.44 (SEM 0.36) mumol/g dw. The energy charge potential (ECP) immediately recovered to 0.79 (SEM 0.01) within 8 min (normal, 0.81, SEM 0.01). Mitochondrial phosphorylation rate (PR) was not significantly altered. LP averaged 451 (SEM 10) nmol/g dw in normal livers and did not change even during reperfusion (504, SEM 79, nmol/g dw, at 15 min). In contrast, in the warm ischemic group, ATP recovered only to 65% of the normal value even at 30 min (P less than 0.01), and TAN remained significantly lower than the control value (12.39, SEM 0.47, mumol/g dw, P less than 0.001). PR was normal at the end of warm ischemia, was significantly reduced at the end of the total ischemic period (P less than 0.001 and P less than 0.01, as compared with control and normal values, respectively), and gradually recovered over 30 min. LP increased and reached the maximum of 795 (SEM 84) nmol/g dw at 15-min reperfusion (P less than 0.05). In grafts treated with 50 mg/kg bw allopurinol (i.v.) 10 min prior to the onset of warm ischemia, ATP and ECP recovered to normal values at 30 min, and TAN was significantly higher than in the warm ischemic group (13.28, SEM 0.28, mumol/g dw, P less than 0.05). PR was maintained at normal values, and LP was increased but to a lesser degree than in the ischemic group. It is concluded that the delayed recovery of ATP metabolism in the warm ischemic group might be due to the loss of adenine nucleotides and the decreased PR, and that allopurinol has a protective effect against warm ischemic damage. PMID- 1897011 TI - Carolina rinse solution--a new strategy to increase survival time after orthotopic liver transplantation in the rat. AB - Recently, we described a new solution, Carolina rinse, that prevents nonparenchymal cell injury in vitro after reperfusion of livers stored in University of Wisconsin cold solution (Currin RT, Toole JG, Thurman RG, Lemasters JJ. Transplantation 1990; 50: 1076). The present study was designed to examine the effect of Carolina rinse on graft survival in vivo. Unlike UW cold storage solution, which is high in potassium, Carolina rinse contains extracellular inorganic ions at levels similar to blood, a calcium channel blocker and a radical scavenger. Carolina rinse also contains fructose and mildly acidotic pH to reduce hypoxic cell death. Livers from Lewis rats were explanted, stored in UW cold storage solution under nonsurvival conditions, and rinsed with either 15 ml of Ringer's, UW solution, Carolina rinse, or Carolina rinse saturated with nitrogen prior to completion of implantation surgery. In the Ringer's rinse group, only 4% of recipients survived 30 days postoperatively. In this group, SGOT levels reached maximal values of about 5000 U/L. Survival was also poor (25%) when grafts were rinsed with UW solution. In the Carolina rinse group, however, 9 of 16 rats (56%) survived indefinitely, and maximal postoperative SGOT levels were reduced 3-fold. Liver injury indexed histologically was also decreased about 3-fold by Carolina rinse compared with the control group rinsed with Ringer's solution. Carolina rinse diminished postoperative sinusoidal endothelial cell damage assessed by electron microscopy and reduced carbon particle phagocytosis due to Kupffer cells significantly. Moreover, Carolina rinse diminished graft swelling and improved postoperative hepatic microcirculation compared with the Ringer's rinse group. Taken together, these results indicate that Carolina rinse is a superior alternative to Ringer's solution in vivo to protect liver grafts from reperfusion injury when removing high-potassium-containing cold storage solutions clinically prior to implantation. PMID- 1897013 TI - Hepatic microcirculatory disturbances due to portal vein clamping in the orthotopic rat liver transplantation model. AB - Most modifications and applications of the orthotopic rat liver transplantation (ORLT) model require clamping of the portal vein, thus leading to ischemia of the gut. The purpose of this study was to evaluate the effect of portal vein clamping during ORLT on hepatic microcirculation and leukocyte--endothelial interaction by intravital fluorescence microscopy. ORLT were performed following 1 hr of cold storage in EuroCollins solution without (standard group) and with insertion of a portojugular shunt (shunt group) to minimize intestinal ischemia. ORLT induced reduction of perfused sinusoids (83%) and velocity of leukocytes (311 +/- 4.5 microns/sec; mean +/- SEM) compared with nontransplanted controls (99% and 417 +/ 4.9 microns/sec). Portojugular shunt during ORLT improved hepatic microvascular perfusion (89% and 355 +/- 3.4 microns/sec; P less than 0.05). Furthermore, percentage of permanent and temporary adherent leukocytes decreased significantly when a portosystemic shunt was applied (from 33.5 +/- 1% to 22.1 +/- 1% and 19.7 +/- 1.2% to 14.0 +/- 0.9%; P less than 0.05). The results of the study reveal that intestinal congestion and reperfusion results in a rise in leukocyte adhesion to the sinusoidal wall and in disturbances of the hepatic microcirculation. It seems likely that increased endotoxin concentrations in the portal vein induce an activation of hepatic macrophages that subsequently cause release of chemoattractant mediators. In conclusion, side effects of intestinal ischemia during experimental liver transplantation surgery on liver function due to release of chemoattractant mediators should be considered when experimental data are transferred to clinical settings. PMID- 1897014 TI - Synergy between cyclosporine and anti-IL-2 receptor monoclonal antibodies in rats. Functional studies of heart and kidney allografts. AB - Although cyclosporine has improved results of organ transplantation, treatment regimens using multiple agents are being evaluated both experimentally and clinically in attempts to diminish its often profound nephrotoxicity; some therapies act synergistically by differential inhibition of distinct steps of the rejection cascade. The effects on graft function of a full dose or a subclinical dose of CsA, ART-18, a monoclonal antibody (mAb) directed against the IL-2 receptor expressed on activated host cells, and a combination of low-dose CsA and ART-18, have been tested in rat recipients of both heart and kidney allografts. Renal graft function was assessed by several classic techniques; heart function by isolated perfusion methods. Full-dose CsA and combination treatment were most effective in both organ graft systems, with at least one-third of grafts surviving indefinitely. At seven days after transplantation, glomerular filtration rates and renal plasma flow of all grafted recipients were decreased as compared with normal; at 14 days, function in the best treatment groups had improved toward that of isografts. Similarly, cardiac output and stroke work index of best treatment groups were comparable to that of isografts. These functional studies complement previously reported immunological and immunohistological findings stressing that synergy occurs between subclinical doses of CsA and anti-IL-2-R mAb in two rat organ graft systems. PMID- 1897015 TI - Lung transplantation in the rat. A morphometric analysis of the gas exchange region. AB - Single-lung transplantation in the rat provides a model that allows investigators to study immunologic, cellular, and morphologic changes associated with allograft rejection. We performed morphometric analysis of transplanted and nontransplanted lungs removed from recipients having received isografts, allografts, or hilus stripping up to six months previously, and having received cyclosporine on the first postoperative day, the second postoperative day, the first five days, or not at all. When CsA was not administered, there was extensive and rapid destruction of the alveolar septa with consolidation and rejection of the transplanted lung within one week. In contrast, the allografts from rats treated with CsA were not obviously changed compared with the control lung. To evaluate whether or not these CsA-treated allografts had even subtle injury to alveolar septal cells, a morphometric analysis using transmission electron microscopy was used. There were no significant changes between control (nontransplanted or hilus stripped) lungs and isografted or allografted lungs for most parameters measured. Exceptions included type I epithelial cell volume, which increased in rats treated with CsA on postoperative day 1 only, and the tissue component of diffusing capacity, which decreased in rats treated with CsA on postoperative day 2 only. We conclude that CsA treatment of rats given lung allografts effectively blocks the development of injury in the gas exchange region. The effect is achieved when the CsA is given during the first five days following transplantation in rats, and may be influenced by the timetable of administration and cumulative dosage. PMID- 1897016 TI - Transplantation of purified frozen/thawed canine pancreatic islet allografts with cyclosporine. AB - We studied the survival of defined volumes of highly purified frozen/thawed islets transplanted into the spleen of 4 groups of apancreatic mongrel dogs (total, 21), with or without cyclosporine from day -4 to day 30: group 1 (controls), without CsA, autograft of mean (+/- SE) islet volume 5 +/- 1 microliters/kg body weight; group 2, single-donor allograft, and group 3, multiple-donor allograft (both, 6 +/- 1 microliters/kg), both with CsA; and group 4, large-volume multiple-donor allograft (24 +/- 1 microliters/kg) with CsA. Grafts were cooled slowly to -40 degrees C, stored at -196 degrees C, and thawed rapidly. The CsA dose was adjusted to maintain whole-blood trough values of 600 800 micrograms/L, and allograft recipients manifesting early hyperglycemia were given insulin to maintain plasma glucose concentration below 150 mg/dl. In group 1, two dogs died early (graft failure in 1, intussusception in 1), but the remaining five were normoglycemic at 30 days. In groups 2 and 3, hyperglycemia ensued from about day 2.5, but 4 of 5 grafts in group 2 and all grafts in group 3 secreted insulin into the splenic vein at 30 days. In group 4, normoglycemia ensued within 24 hr of transplantation and was maintained in all 6 dogs for 30 days; the grafts failed 15 +/- 2 days after CsA was stopped. The data demonstrate prolonged function of purified frozen/thawed islets after transplantation into these outbred dogs but indicate a need for a greater volume of allogeneic islets from multiple donors than of autologous islets to achieve normoglycemia. PMID- 1897017 TI - Improvement of the effects of intrasplenic transplantation of hepatocytes after 90% hepatectomy in the rat by cotransplantation with pancreatic islets. AB - Acute liver failure is associated with high mortality. Whether support with transplanted hepatocytes improves the outcome is not established. We studied the potential beneficial effects of intrasplenic transplantation of hepatocytes in conjunction with islets of Langerhans on 90% hepatectomy-induced acute liver failure in rats. We found that all control rats died within 48 hr following 90% hepatectomy. In contrast, the mortality decreased significantly in rats transplanted with 10(7) hepatocytes into the spleen parenchyma at 1-3 days prior to 90% subtotal hepatectomy, whereas no significant reduction in mortality was seen in rats transplanted with hepatocytes immediately after the operation. However, cotransplantation of hepatocytes and 400 isolated pancreatic islets into the spleen reduced mortality when performed immediately after the 90% hepatectomy. Therefore, hepatocyte transplantation reduces mortality after 90% hepatectomy only if performed prior to the hepatectomy. However, transplantation of hepatocytes in conjunction with pancreatic islets reduces mortality when performed at the same time as 90% hepatectomy. Hence, the combined transplantation of hepatocytes and islets might offer support after liver failure. PMID- 1897018 TI - Allograft vein patency in a canine model. Additive effects of cryopreservation and cyclosporine. AB - Autogenous saphenous vein is the preferred conduit for many cardiovascular operations. Attempts to use allograft veins for arterial reconstruction have had poor results. To define circumstances under which allograft veins might prove to be acceptable vascular conduits, dogs underwent femoral artery bypass using reversed saphenous veins. Veins were transplanted fresh or after cryopreservation. Group I dogs received a fresh autograft to replace one femoral artery (group I F) and a cryopreserved (CP) autograft (group I C) to replace the other. Group II dogs received fresh allograft veins, and group III received CP allograft veins, neither group receiving additional treatment. Group IV received fresh allograft veins and Group V received CP allograft veins; both groups received cyclosporine 15 mg/kg. Animals were maintained until grafts occluded or until six months elapsed. Patency was observed in all group I F grafts throughout the observation period. Six-month patency rates in the other groups were: group I C, 9/10 (P = NS vs. group I F); group II, 0/10 (P less than 0.01), group III, 0/10 (P less than 0.01), group IV, 1/10 (P less than 0.01), group V, 7/11 (P = NS). In a separate series of observations 10 cryopreserved allograft veins were implanted in 10 dogs that received CsA for 30 days. CsA was then discontinued. All of these grafts occluded within 30 days of discontinuing the CsA. Long-term patency of saphenous vein allografts was achieved only with the combination of cryopreservation and immunosuppression with continued CsA. PMID- 1897019 TI - Treatment of corneal allograft rejection with the cytotoxin IL-2-PE40. AB - IL-2-PE40 is a recombinant chimeric protein composed of IL-2, fused to a modified pseudomonas exotoxin. This molecule is extremely toxic to activated T cells expressing high-affinity IL-2R. We used this new molecule for selective immunosuppression to treat corneal allograft rejection in the rat, using Fisher and Lewis rats, a strain combination differing only in medial and minor histocompatibility antigens. The effect of IL-2-PE40 on the immunologic response was studied using both a heterotopic corneal graft model and orthotopic grafts. At the dose of 0.31 micrograms/g given intraperitoneally every 12 hr, IL-2-PE40 produced a significant reduction of both total lymph node cells and cytotoxic-T cell (CTL) activity in draining lymph nodes (DLN) of heterotopically grafted animals. IL-2-PE40 treatment also significantly reduced the clinical rejection score and cumulative rejection rate (CRR) in orthotopic grafts and appears to be a very effective immunosuppressive agent. PMID- 1897020 TI - Possible role of extracellularly released phagocyte proteinases in coagulation disorder during liver transplantation. AB - Orthotopic liver transplantation is frequently associated with a complex coagulation disorder, influencing the outcome of the procedure. In this respect, disseminated intravascular coagulation (DIC) had been suggested to be of causative importance for bleeding complications after reperfusion of the liver graft. In 10 consecutive patients undergoing orthotopic liver transplantations, we studied the occurrence of two phagocyte proteinases of different origin in the graft liver perfusate and in systemic blood during the operation, as well as their effects on hemostasis. As compared with plasma samples taken at the end of the anhepatic phase, highly significant increases of cathepsin B and thrombin anti-thrombin III complexes (TAT), as well as highly significant decreases in antithrombin III, protein C, and C1-inhibitor were observed in graft liver perfusate. Von Willebrand factor and fibrinogen were slightly decreased, whereas the elastase-alpha 1 proteinase inhibitor complexes (EPI) were elevated. In plasma the activity of cathepsin B remained unchanged during the prereperfusion phases, but immediately after revascularization of the graft this cysteine proteinase increased. The EPI showed a gradual increase in plasma during the preanhepatic and anhepatic phases but a more pronounced increase in the reperfusion phase. In parallel with the rise in these two proteinases TAT increased and the activities of antithrombin III and C1-inhibitor in plasma decreased after reperfusion. At 12 hr after revascularization plasma levels of TAT, antithrombin III, and C1-inhibitor had returned to the prereperfusion ranges, whereas cathepsin B and EPI were significantly above the baseline levels. These observations are consistent with the hypothesis that extracellularly released lysosomal proteinases may play a role in the development of a DIC-like constellation, including thrombin formation after revascularization of the liver graft. For the first time we could prove the occurrence of phagocyte proteinases in graft liver perfusate and evaluate the importance of these proteinases for the understanding of the pathophysiology leading to bleeding complications in patients undergoing orthotopic liver transplantation. PMID- 1897021 TI - Histocompatibility and other risk factors for histological rejection of human cardiac allografts during the first three months following transplantation. AB - A histological analysis of 2564 endomyocardial biopsies was conducted in 349 cardiac transplant patients to determine potential risk factors for acute cellular rejection during the first three months following transplantation. This analysis dealt with the frequency, time of onset, and duration of cellular rejection. Patients on perioperative RATG experienced significantly less rejection than patients on OKT3 or without antilymphocyte antibody immunoprophylaxis. A trend was noted toward increased rejection in recipients diagnosed originally with chronic myocarditis compared with patients in other disease categories including ischemic heart disease and dilated cardiomyopathy. No significant differences were seen in histological rejection between male and female recipients. On the other hand, patients over 55 years of age were found at lower risk of histological rejection. The results of this analysis have demonstrated quite clearly, but not unexpectedly, that a greater degree of HLA mismatching correlates with increased cellular rejection. This effect was noted not only for the HLA-A,B and DR antigens, but also HLA-DQ and HLA-DRw52/53 antigens. In multivariate analysis, the highest level of statistical significance was obtained for the combined HLA-A,B,DR and DQ group. Sensitized patients with panel-reactive lymphocytotoxic antibodies of greater than 10% experienced more histological rejection than nonsensitized patients. On the other hand, a positive lymphocytotoxic crossmatch did not appear to influence cellular rejection of cardiac allografts. Also, no differences were seen in histological rejection between ABO-identical and compatible heart transplants. These findings further support the concept that donor HLA compatibility and pretransplant sensitization represent significant risk factors for cellular rejection in cardiac transplantation. PMID- 1897022 TI - The increased risk of fatal liver disease in renal transplant patients who are hepatitis Be antigen and/or HBV DNA positive. AB - To determine whether active viral replication is associated with increased morbidity and mortality in chronic carriers of hepatitis B virus (HBV) undergoing renal transplantation, we reviewed 23 years of experience at our hospital. Over the period 1966-1989, 42 chronic carriers of hepatitis B surface antigen (HBsAg) received renal transplants, 32 of whom had functioning grafts for 12 months or longer. Stored sera were tested for markers of hepatitis B virus, hepatitis C virus (HCV), and hepatitis delta virus (HDV) infection, and the serologic findings were correlated with clinical and biochemical data. The presence of HBV DNA and/or hepatitis Be antigen (HBeAg) in serum samples collected prior to transplantation was associated with an increased probability of death from liver disease. Whereas 5 of 10 patients in this group died of chronic liver disease, only 1 of 15 patients who were HBV DNA and/or HBeAg negative prior to transplantation died of liver disease. This difference is highly significant (P less than 0.02). No difference in outcome was attributable to age at transplantation, gender, country of birth, or the presence of abnormal hepatic transaminase levels prior to transplantation. PMID- 1897023 TI - Cyclosporine's effect on insulin secretion in patients with kidney transplants. AB - Adverse effects of cyclosporine on glucose metabolism have been reported in patients with kidney transplantation, but steroids were present in all the immunosuppressive schedules evaluated. We have studied endocrine pancreatic function (OGTT measuring plasma insulin [IRI] and c-peptide [CP]) in 3 groups of patients, matched for age and body-mass index, 16-66 months after functioning Ktx. Seven patients were treated with CsA monotherapy (group I), 7 patients with CsA plus prednisone (group II), and 6 patients with azathioprine plus prednisone (group III). Seven healthy subjects formed the control group. OGTT was normal in all patients, except one in group II (impaired glucose tolerance). There were no significant differences between the 4 groups concerning fasting blood glucose and area under the glucose curve, as well as basal insulin levels, peak insulin response to glucose, and area under the insulin curve. Basal CP, peak CP response to glucose, and area under CP curve were lower in CG than in the 3 groups of patients. Basal CP in group II (4.4 +/- 2.2 ng/ml) was higher than in group I (2.8 +/- 0.6 ng/ml, P less than 0.05). Glucose/IRI molar ratio in group II (5.7 +/- 1.4, P greater than 0.05) was lower than in group I (7.3 +/- 1.8) and CG (8.0 +/- 2.1, P less than 0.025). Our results suggest that CsA at normal dosage has no clinically important effect on beta-cell function. The indirect evidence of insulin resistance observed in patients treated with CsA plus prednisone is ascribable to corticosteroid treatment. PMID- 1897024 TI - Plasma pancreatic secretory trypsin inhibitor as a marker of pancreas graft rejection after combined pancreas-kidney transplantation. AB - One of the major problems in clinical pancreas transplantation is the lack of a simple and sensitive marker for detecting the early process of allograft rejection. Plasma pancreatic secretory trypsin inhibitor (p-PSTI) levels were measured in recipients of combined pancreas-kidney transplants (SPKT) and isolated cadaveric renal transplants (CRT) as controls. In the postoperative courses of SPKT recipients without acute rejection episodes and any other complications, high preoperative and immediate postoperative concentrations of p PSTI gradually declined from the third day after transplantation and returned to the baseline level (less than 87.9 ng/ml) by the 6th day, and then remained unchanged. In this study, 11 out of 17 SPKT recipients experienced 13 acute rejection episodes. Early in the rejection course, p-PSTI levels increased significantly (P less than 0.05) 1 day before the initial day of diagnosed rejection (peak value; 232.7 +/- 99.3 ng/ml), and then they decreased following antirejection therapy. In the control group, p-PSTI elevation was less dramatic (peak value: 70.5 +/- 22.8 ng/ml, P less than 0.01) and did not precede the rise in serum creatinine. We conclude that p-PSTI may be an early, sensitive, and reliable marker of clinical pancreas graft rejection. PMID- 1897025 TI - Mechanical and electrophysiologic changes in rat cardiac allografts during immunologic rejection. AB - We studied the relationship between immunologic rejection and changes in contractility of isolated perfused papillary muscle, using heterotopically transplanted rat hearts. Rejection assessed by mononuclear cell infiltration was associated with depressed twitch amplitude and lower rates of tension development and relaxation. The relationship between maximum developed tension and [Ca2+]o was attenuated in muscle from the rejecting allografted heart, as compared with muscle of normal or isografted hearts. To determine the effects of rejection on ventricular electrophysiologic properties, we recorded transmembrane action potentials in isolated ventricular myocardium. We found that in rejecting allografted hearts the resting potential, action potential amplitude, and maximum upstroke velocity of phase zero were significantly reduced compared with normal and isografted hearts. The attenuation in the mechanical and electrophysiologic properties was largely prevented by treating the transplanted rat with anti lymphocyte-globulin on days 0, 1, and 2 after transplantation. In summary, the present study demonstrates that immunologic rejection of the heterotopically allotransplanted rat heart is associated with marked attenuation of both mechanical and electrophysiologic properties of the ventricular myocardium. PMID- 1897026 TI - Immune responses elicited by transplantation and tissue-restricted antigens expressed on retinal tissues implanted subconjunctivally. AB - In recent years there has been renewed interest in experimental retinal transplantation. Immunological rejections represent a major barrier to the success of retinal transplants. We recently reported that strongly histoincompatible neuroretinal grafts placed in the subconjunctival space of adult recipient mice were rejected, whereas similar grafts placed in the anterior chamber of the eye were accepted. Since retinal tissues are known to express retina-restricted autoantigens that can induce specific systemic immune responses and can serve as targets of destructive autoimmune attack, it is important to determine whether retinal transplants can evoke immune responses directed at retina-restricted antigens, and whether such responses might be deleterious to the graft. In this study, neonatal neural retinal grafts were placed into the subconjunctival space of eyes of normal allogeneic and syngeneic mice. Delayed hypersensitivity to the relevant alloantigens and to putative retina-restricted autoantigens was assayed. The results reveal that neural retina grafts sensitized their recipients to both alloantigens and retina-specific autoantigens. Moreover, in some recipients, a delayed, destructive uveitis developed, implying that graft elicited immune responses directed at retina-restricted antigens may provoke autoimmune reactions in previously normal eyes of recipients. These findings indicate that grafts of developing neural retina tissue express both transplantation antigens and retina-restricted antigens in immunogenic form, and that grafting leads to systemic immunization against both sets of antigens. PMID- 1897027 TI - Suppression of graft-versus-host reactivity by a single host-specific blood transfusion to prospective donors of hemopoietic cells. AB - Delayed-type hypersensitivity responses against recipient's histocompatibility antigens can occur early in the course of a graft-versus-host reaction in lethally irradiated allogeneically reconstituted mice. This reactivity could be suppressed by a single host-specific blood transfusion to the prospective donors of allogeneic spleen cells. Maximum suppression was found when the blood transfusion was given 4 or 5 days before the mice were used to reconstitute lethally irradiated hosts. Whole blood and purified white blood cells were capable of inducing suppression, whereas purified red blood cells, plasma, and serum were not. Suppression was already detectable after administration of 1 microliters of whole blood and virtually complete at a dose of 1.0 ml. Irradiation of the blood reduced but did not abrogate its capacity to induce suppression. Purified B and purified T lymphocytes appeared equally effective in inducing suppression. Two helper T cells clones, a Th1 and a Th2 clone, were able to induce suppression as well. A high dose of recombinant IL-2, injected daily for 5 days after reconstitution, did not abrogate or reduce the suppression. Suppression could be induced by H-2 as well as non-H-2 alloantigens, separately or together. A pure H-2-incompatible transfusion was more effective in inducing suppression than a pure non-H-2-incompatible one. Suppression appeared to be a dominant phenomenon and was mediated by a Thy-1+, CD4+, CD8- spleen cell population. This T cell population had its origin in the transfused donor, which excludes the possible involvement of blood-derived "veto-cells." PMID- 1897028 TI - Combined small bowel and liver transplantation in the rat: possible role of the liver in preventing intestinal allograft rejection. PMID- 1897029 TI - Ketoacidosis in patients undergoing foregut resection and orthotopic liver transplantation. PMID- 1897030 TI - Evidence that a solubilizing agent has no effect on cyclosporine-associated hyperpotassemia. PMID- 1897031 TI - Accessory right hepatic duct stricture following liver transplantation. PMID- 1897032 TI - Sterilization of human small intestine allograft biopsies for later immunologic studies. PMID- 1897033 TI - Evidence that antibodies eluted from rejected kidneys of HLA-identical transplants define a non-MHC alloantigen expressed on human kidneys. PMID- 1897034 TI - Orthotopic liver transplantation in the mouse. PMID- 1897036 TI - Isogeneic islet transplantation. The effect of gamma irradiation. PMID- 1897035 TI - The need for glutathione and allopurinol in HL solution for rat liver preservation. PMID- 1897037 TI - Failure of pretreatment with cyclosporine to reduce ischemic liver injury after hepatic artery ligation in pigs. PMID- 1897038 TI - Persistence of oscillatory insulin secretion in denervated islet cell autografts. PMID- 1897039 TI - [Drug committees--help to self-help]. PMID- 1897040 TI - [Drug committee--an example of a quality circle]. AB - A theoretical comparison was undertaken between the work of the drug committee and that of the quality circle in order to investigate whether quality circles are suited as methods for organisation of ensuring the standard of quality in Danish hospitals. On the basis of an investigation of the pharmaceutical service in hospitals, the work of the drug committees was analysed and assessed. The authors found that drug committees which worked according to quality circle principles achieved their goal: To rationalise the employment of drugs in routine treatment. The authors consider that formation of quality circles is a suitable method of ensuring quality in Danish hospitals but it would probably be of decisive significance for the result that the hospital direction assumed its responsibility for the results and for coordination of the circles. PMID- 1897041 TI - [Are the recommendations of the drug committee followed? A comparison of the prescribing pattern of anti-angina drugs in general practice and hospitals in relation to the recommendations]. AB - The object of this investigation was to describe the choice of recommended/non recommended anti-anginal preparations in a group of patients in a hospital and prescribed by the general practitioner on discharge and during the subsequent three years. Eighty-nine patients participated in the investigation. Sixty-nine of these received medicinal treatment at the conclusion of the period. The investigation demonstrates that the recommendations by the Danish Drug Committee were followed in 90% of the cases during the last year of observation. It is concluded that the activities of the Danish Drug Committee may influence the choice of anti-anginal preparations on discharge from hospital and during the subsequent three years. PMID- 1897042 TI - [Therapy control of perphenazine in paranoid conditions. 1. Organizational aspects]. AB - A prospective investigation was carried out in the Department of Psychiatry, Odense University Hospital, on therapy control by serum monitoring of the neuroleptic, perphenazine for a period of one year. Newly admitted patients requiring treatment for paranoid symptoms, excluding mania, were offered medication with perphenazine (fixed dosage, oral or parenteral (depot)) which would be serum-monitored. A global record was made of the therapeutic effect and the side-effects by the physicians in the department. In the investigation period, 605 admissions were registered in the department, of them 363 were prospectively registered in the investigation. In all 199 were found to satisfy the inclusion criteria. Either one or two blood tests were carried out on each of 141 patients in the treatment period, i.e. six weeks. The gap in registration is consistent with the result from other investigations. Participation in the investigation varied from ward to ward (33%-87%). The reason for the variation is mainly due to different treatment procedures and traditions. The main conclusion drawn from the investigation is that it is possible to set up a stable treatment/serum-monitored system. In the majority of cases, the team of physicians in the department succeeded in finding the dosage most appropriate on the basis of the serum concentration level. Laboratory recommendations were followed in 93% of the cases. PMID- 1897043 TI - [Therapy control of perphenazine. 2. Clinical aspects]. AB - Rational use of serum concentration monitoring of the neuroleptic, perphenazine, was evaluated in a prospective investigation. A total of 141 hospitalized patients with paranoid symptoms (excluding mania) requiring treatment were included during the investigation period (one year). Perphenazine was administered (fixed doses) orally (92 patients) and parenterally (depot, decanoate, 45 patients) in a six-week treatment period. Serum concentrations of perphenazine were monitored after 10-14 days oral treatment, on the 14th and 21st days after the commencement of depot treatment. The patients were steered on to the recommended therapeutic range for perphenazine (1.5-6 nmol), according to the serum level measured. Global clinical assessment was carried out by the departmental physicians. Therapy control of perphenazine by serum monitoring was an important supplement to the clinical evaluation of therapeutic effect. Fifteen (65%) out of 23 patients who were treated orally with insufficient therapeutic effect, showed non-compliance or elevated metabolism. On the basis of a single serum concentration measurements (12 hours values), it proved possible to steer the majority of patients onto the recommended therapeutic level. In this way, the individual patient reached optimal therapeutic effect with a minimum of side effects. PMID- 1897044 TI - [Plasma fibrinogen and cardiovascular disease]. AB - In prospective epidemiological studies the plasma fibrinogen level is correlated to cardiovascular diseases even after statistical correction for the major risk factors. The fibrinogen level is positively correlated with many risk factors such as life-style variables including smoking, lack of physical activity and high-fat diet. Psychosocial variables are in many studies closely correlated with the fibrinogen level even after adjustment for the traditional (established) risk factors. PMID- 1897045 TI - [Myotonic dystrophy]. AB - Myotonic dystrophy (MD) is illustrated by a characteristic case report. MD is a dominantly inherited multi-organic disease with complete penetrance, but with highly variable expression illustrated by the near relatives of this patient. The disease usually follows a slow, progressive course. The cardinal symptoms are myotonia, muscle atrophia, cataract and a characteristic facial appearance. Cardial arrhythmias, endocrine and mental changes also occur. The liability to arrhythmias and the weakened respiratory muscles of the patients which lead to ventilatory insufficiency makes anesthesia and surgical operation risky. The diagnosis, which is made by electromyography, is easy in typical cases, but suspicion that the disease is present is seldom raised in very mild cases if there is no recognition of familial cases. Meticulous examination of near relatives of severe cases is therefore essential to take advantage of the possibilities of prenatal diagnosis recently made possible through developments in DNA technology. PMID- 1897046 TI - [Diabetic examination in general practice. Screening of a practice population and a study of occurrence]. AB - In a general practice, a screening examination for diabetes mellitus by measuring blood glucose in capillary blood was performed. A total of 2,843 persons aged 20 80 years were invited, 1,973 (69.4%) participated. At screening, 66 possible cases (BG greater than or equal to 8 mmol/l) were found. Among these, 16 diabetics were found, nine of whom had predisposing conditions. The prevalence of diabetes mellitus in the examined and known population of the practice was found to be 2.5% and calculated to be 2.2% in the total population of the practice. It was demonstrated that an investigation of this kind can be carried out but felt laborious and interfered with the daily work. Nevertheless, hitherto unknown diabetics were detected and instructed. A method of finding diabetics in general practice is thus described. The method is probably effective, as the prevalence of diabetes mellitus reached the expected, when the known and newly found diabetics were added. PMID- 1897047 TI - [From psychiatric hospitals to local municipal departments. The county of Vejle 1973-1987]. AB - On April 1, 1976 the Danish State handed over the responsibility for treatment of psychiatric patients to the counties. None of the state hospitals were situated in the county of Vejle. The changes of the admission pattern of the inhabitants of Vejle county aged 15+ years during the years from 1973 to 1987 are described. The annual bed occupancy per 1,000 inhabitants decreased markedly during the period (from 829 in 1973 til 366 in 1986) while the admission rates were relatively stable. Vejle county has successfully reduced the number of admissions to mental hospitals in other counties, but was, however, still not self sufficient in 1987. The decrease in bed occupancy was significant in the groups of schizophrenia, manic-depressive psychosis, organic states, neurosis, alcohol and drug addiction, while in the group of other psychoses and other conditions the decrease was not significant. In the group of personality disorder the bed occupancy increased, but not significantly. PMID- 1897048 TI - [HIV-positive persons in a Danish provincial region 1985-1990]. AB - From January 1985 to July 1990 a total of 128 HIV-infected persons were examined in the Clinics for Infectious Diseases and Dermato-Venereology at Odense University Hospital which covers a provincial region of Denmark. Clinical and demographic data were recorded regarding their initial contact with the hospital. About 1/2 (47%) were homosexual men and these were seen primarily during the first and last years of the observation period. Approximately 1/4 (27%) were intravenous drug users (15% of these were women), and about 1/5 (18%) had become infected by heterosexual relations. Half of these were women and these were seen mostly during the latter half of the observation period. The majority (81%) were clinically healthy at the time of the initial contact with the hospital. Eight patients (6%) had developed AIDS. It is noteworthy that during the last year of the observation period, there was a great increase in the number of homosexuals with compromised health and low CD4-cell count. This tendency could not be demonstrated for the other groups. In general, at the beginning of the observation period, a very uniform group of homosexual men was observed. Most of these had become HIV-infected in Denmark. They were healthy and with good immunological function and in the age group 25-49 years. During the subsequent years, a more varied group of patients was observed. The risk behaviour was different, the percentage of women greater and there was greater variation in age, health status and CD4-count.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1897049 TI - [Incidence and treatment of urinary calculi in patients in Frederiksborg County]. AB - The case records of all patients admitted to one of the hospitals in the County of Frederiksborg with radiologically demonstrated first episodes of urinary calculi during a period of one year in 1983/1984 and 1988/1989 respectively were reviewed retrospectively. Uniform frequencies of calculus incidence and sex distribution were encountered mutually and as compared with the remainder of Denmark during the two periods. In 30% of the cases the calculi were localized to the kidneys and in 58% to the ureter. In approximately 65% of the patients, the greatest diameter of the stones was 100 mm or less. Spontaneous passage of the stones occurred in approximately 40%. Development in the treatment of urinary tract stones has followed the development in the county as a whole. The number of operative interventions during the five year period was reduced by 30% and extracorporeal shock wave treatment was employed in 22% during the second period. PMID- 1897050 TI - [Vibrio vulnificus]. AB - A patient sustained a knife wound while cleaning eels and subsequently severe wound infection developed. Vibrio vulnificus was isolated from the wound and, on the basis of this, the main features of the epidemiology of the bacteria and the typical clinical pictures are reviewed. PMID- 1897051 TI - [Acute iridocyclitis with fever and liver involvement during quinidine therapy]. AB - Acute iridocyclitis is a rare hypersensitive reaction to quinidine treatment. The third case in the literature is reported here. A woman aged 80 years developed pyrexia, anorexia, nausea, skin rash and hepatic dysfunction after treatment with quinidine for two weeks. Four weeks later, while still receiving quinidine, she developed acute iridocyclitis. Quinidine treatment was withdrawn, the eye symptoms were treated and the patient recovered rapidly without complications. This case report draws attention to quinidine as a possible cause of iridocyclitis of unknown origin. PMID- 1897053 TI - [Non-scientific reflections on the phenomenon of obesity]. PMID- 1897052 TI - [Hemoperfusion in theophylline poisoning]. AB - On account of increased employment of theophylline depot preparations, theophylline intoxication occurs relatively frequently. A case report is briefly reviewed to describe the symptoms of poisoning and the principles of treatment. Particular emphasis is placed on discussion of the indications for carbon column haemoperfusion. PMID- 1897054 TI - [Diagnosis of Pneumocystis carinii pneumonia in HIV-positive patients]. PMID- 1897055 TI - [Mammography screening]. PMID- 1897056 TI - [Ascites]. PMID- 1897058 TI - [Physicians visiting pharmacies--a deep sigh]. PMID- 1897057 TI - [Sandoparin dihydroergotamine. A combination preparation for prevention of thrombosis]. PMID- 1897060 TI - Reduction in band 3 protein of red cells in sickle cell anaemia. AB - Twelve patients suffering from sickle cell anaemia (Hb less than 75 g/l) with SS haemoglobin were studied with special regard to Band 3-protein content in their erythrocyte membranes on SDS-PAGE. They were compared in this respect with 7 asymptomatic individuals with AS-haemoglobin and 10 healthy controls with the ordinary adult haemoglobin. A heterogeneity in Band 3-protein content was evident among the 12 patients. Six of them belonged to a low content group while the other 6 belonged to a high content group comparable with the asymptomatic subjects and the controls. No simple relationship seemed to exist between Band 3 protein reduction and the clinical presentation. PMID- 1897059 TI - New perspectives on the structure and function of the normal and diabetic beta cell. PMID- 1897061 TI - Does non-ionizing radiant energy affect determination of the evaporation rate by the gradient method? AB - A study was performed to investigate whether measurements of the evaporation rate from the skin of newborn infants by the gradient method are affected by the presence of non-ionizing radiation from phototherapy equipment or a radiant heater. The evaporation rate was measured experimentally with the measuring sensors either exposed to or protected from non-ionizing radiation. Either blue light (phototherapy) or infrared light (radiant heater) was used; in the former case the evaporation rate was measured from a beaker of water covered with a semipermeable membrane, and in the latter case from the hand of an adult subject, aluminium foil or with the measuring probe in the air. No adverse effect on the determinations of the evaporation rate was found in the presence of blue light. Infrared radiation caused an error of 0.8 g/m2h when the radiant heater was set at its highest effect level or when the ambient humidity was high. At low and moderate levels the observed evaporation rate was not affected. It is concluded that when clinical measurements are made from the skin of newborn infants nursed under a radiant heater, the evaporation rate can appropriately be determined by the gradient method. PMID- 1897062 TI - Metabolic control, residual insulin secretion and self-care behaviours in a defined group of patients with type 1 diabetes. AB - A population of 185 type 1 diabetes patients (insulin-dependent, IDDM), 25-45 years old, was studied retro- and prospectively over a 9-year period with the aim of analysing background factors of importance for the ability to perform adequate self-care. Expressed as mean HbA1c, the metabolic control was slightly improved at the end of the study, when the insulin schedule had been changed in 60% of the patients to multidose treatment. The degree of metabolic control remained constant over the years. The impact of residual insulin secretion, measured as 24 hour urinary C peptide, was low. Patients with less good metabolic control often had a poor educational background and made less use of self-monitoring of blood glucose (SMBG); they also experienced difficulties with SMBG. The applied knowledge of diabetes also differed between groups with good and poor control. Subjectively, most patients considered their metabolic control to be good, irrespective of the HbA1c values. When asked about their own diabetes complications, their answers were often discrepant from the medical records. Patients with particularly "good" or "poor" metabolic control were on the whole less satisfied with the education and information received than those with intermediate blood glucose regulation. Development of strategies for individually adjusted education seems important. PMID- 1897063 TI - Does exercise stress alter susceptibility to bacterial infections? AB - Swimming was used for evaluating alterations in performance capacity and as a means for studying the influence of exercise stress on susceptibility to Streptococcus pneumoniae and Francisella tularensis infections in two strains of rats, i.e. Fisher-Dunning (FD) and Sprague-Dawley (SD). The performance capacity was reduced by both diseases and was correlated to the dose of the given micro organism. FD rats, however, were more susceptible to the infection and showed a greater deterioration than SD rats. The effects of exercise stress on disease lethality varied with the time that it was performed. Strenuous exercise immediately before infection drastically reduced susceptibility to either of the bacteria, while a similar bout of exercise performed after infection increased disease-related mortality in both diseases. PMID- 1897064 TI - Potassium and blood pressure. AB - The relationships between serum potassium and urinary excretion of potassium and blood pressure were determined in an unmedicated adult population with a wide range of blood pressure (mean arterial blood pressure 100-130 mm Hg, n = 71). Inverse correlations between both serum potassium concentration and urinary excretion of potassium and standing (but not supine) mean blood pressure were seen (r = -0.41, p less than 0.005 and r = -0.33, p less than 0.01 respectively). These relationships persisted also when the influences of age, sex, obesity and kidney function were taken into account in a multiple regression analysis. The present observation is in accordance with previous reports of an association between potassium metabolism and blood pressure. PMID- 1897065 TI - CT evaluation of active adrenal histoplasmosis. AB - We describe three patients with puzzling systemic illnesses in whom computed tomography (CT) led to the diagnosis of active adrenal histoplasmosis. CT was performed in two patients because of gastrointestinal symptoms and weight loss and in the third because of fever developing 2 years after an apparent cure of histoplasmosis. All three patients had adrenal enlargement on CT with features of granulomatous adrenal disease in two. Hormone assays performed after CT supported the diagnosis of adrenal insufficiency and fine-needle adrenal aspiration biopsy with special stains of the aspirates showed histoplasma organisms in all three patients. The combination of adrenal enlargement on CT and laboratory findings of adrenal insufficiency should suggest the diagnosis of histoplasmosis, especially in endemic areas. PMID- 1897066 TI - Transitional cell carcinoma of the bladder in children: radiologic appearance and differential diagnosis. AB - Primary epithelial tumors of the bladder are rare in children. We report a case of transitional cell carcinoma (TCCa) of the bladder in a 10-year-old boy who was evaluated with intravenous urography, ultrasonography, and computed tomography (CT). The radiographic appearance and a differential diagnosis are discussed. The literature of TCCa of the bladder in children is reviewed. PMID- 1897067 TI - Comparison of the digital rectal examination, endorectal ultrasound, and body coil magnetic resonance imaging in the staging of adenocarcinoma of the prostate. AB - A series of 25 patients with biopsy proven adenocarcinoma of the prostate underwent preoperative staging evaluation with a digital rectal examination, endorectal ultrasound, and body coil magnetic resonance imaging (MRI) before their radical retropubic prostatectomy. The sensitivity and specificity of the digital rectal examination for the detection of extracapsular disease were 17 and 100%, respectively. The sensitivity and specificity of endorectal ultrasound for the detection of extracapsular disease were 35 and 89%, respectively. The sensitivity and specificity of body coil MRI for the detection of extracapsular disease by adenocarcinoma of the prostate were 47 and 63%, respectively. Microscopic disease of the capsule and seminal vesicles was the principle reason for understaging by both imaging modalities. This small series suggests that both imaging modalities are marginally more sensitive, albeit less specific, for extracapsular disease of the prostate than the digital rectal examination, with ultrasound having a slight edge in specificity and MRI having a slight edge in sensitivity. PMID- 1897068 TI - Granulomatous prostatitis: a hypoechoic lesion of the prostate. AB - Numerous benign and malignant entities can disrupt the normal prostatic parenchymal architecture producing hypoechoic lesions in the peripheral zone. We report two cases of granulomatous prostatitis mimicking carcinoma. The differential diagnosis of hypoechoic lesions and the etiologies of granulomatous prostatitis are discussed. All hypoechoic lesions in the peripheral zones of the prostate require biopsy for histologic diagnosis. PMID- 1897069 TI - Cowper's glands duct: radiographic findings. AB - Lesions of Cowper's glands duct are uncommon findings in a urethrogram. Three types of anomaly are described in 11 patients. The most frequent type is a slightly dilated duct, which is usually asymptomatic, with or without associated urethral pathology. The other less common types are perforate Cowper's duct and retention cyst, which are usually symptomatic and not associated with other urethral pathologies. PMID- 1897070 TI - Penile hemangioma: US and MR imaging demonstration. AB - A case of a penile hemangioma is reported. The mass had hypoechogenicity on ultrasonography (US) and high signal intensity on T2-weighted magnetic resonance (MR) image. MR images clearly demonstrated the extent of the lesion, especially deep extension into the corpus cavernosum. PMID- 1897071 TI - Complex tunica albuginea cyst simulating an intratesticular lesion. AB - Cysts of the tunica albuginea are uncommon lesions of the testis which in all reported cases have been benign. Complex cysts of the tunica albuginea can mimic intratesticular lesions, thus necessitating orchiectomy. We present a case of a complex tunica albuginea cyst which mimicked an intratesticular lesion at sonography, as well as at magnetic resonance imaging (MRI). Tangential views, however, suggested that this was in fact an extratesticular lesion. The use of tangential views, as well as knowledge of the appearance of the tunica albuginea at MRI, are important to make this differentiation in order to guide the management of these lesions. To our knowledge, this is the first case in which the appearance of a tunica albuginea cyst at MRI has been described. PMID- 1897072 TI - Young male with irritative voiding symptoms and 30-lb weight loss. PMID- 1897073 TI - Cystic renal masses: usefulness of the Bosniak classification. AB - To determine the usefulness of the Bosniak classification of cystic renal masses, the computed tomographic (CT) and ultrasound findings of 16 pathologically proven cystic renal masses were retrospectively reviewed. All imaging studies were reviewed and categorized utilizing the Bosniak classification without knowledge of the final pathologic diagnosis. There were no category I lesions (classical simple cyst), four category II (minimally complicated), seven category III lesions (more complicated), and five category IV lesions (probable malignant). All category II lesions were benign, all category IV lesions were malignant. Of the seven category III lesions, three were benign and four were malignant. We conclude that the Bosniak classification is extremely useful in the management of cystic renal masses. PMID- 1897074 TI - Difficulties in classifying cystic lesions of the kidney. PMID- 1897075 TI - Clinical and imaging features of rhabdoid tumor of the kidney. AB - Rhabdoid tumor of the kidney (RTK) is a rare, highly malignant neoplasm of childhood. The clinical profile of this neoplasm differs from that of Wilms' tumor. We present two cases of RTK. In both our cases, large bulky masses with poorly defined margins and calcifications were demonstrated. The clinical and imaging findings are compared with other childhood renal neoplasms. PMID- 1897076 TI - Cross-sectional imaging of idiopathic solitary renal vein varix: report of two cases. AB - Two cases of solitary renal vein varices are reported which presented as incidental findings on abdominal computed tomography (CT) and were initially thought to represent retroperitoneal lymph nodes. Contrast-enhanced CT, magnetic resonance imaging (MRI), and Doppler ultrasound (US), all demonstrated the vascular nature of these masses suggesting the correct diagnosis. When a rounded soft tissue density mass is seen on noncontrast-enhanced CT either in or contiguous to the renal hilum, a renal vein varix must be excluded. Doppler US, MRI, or dynamic contrast-enhanced CT should be done to exclude a renal varix as the cause. PMID- 1897077 TI - Fracture complications. An overview. AB - No surgical procedure is free of complications. Determining the reason that a complication of a fracture repair occurred and developing a treatment plan are important if the objectives of fracture treatment are to be met. It is also necessary to deal with owners, and, sometimes, other veterinarians in meeting these objectives. PMID- 1897078 TI - Fracture complications. PMID- 1897079 TI - Biomechanics of fracture fixation failure. AB - This article reviews the physiologic forces, stresses, and strains in normal bones. Biomaterials used in implants for fracture fixation devices are described, and the mechanical properties of an implant are discussed. The common mechanisms of implant failure are included. PMID- 1897080 TI - Complications of fractures repaired with plates and screws. AB - The complications associated with bone plates and screws often are related to undersized or oversized implant selection, improper number of implants, inadequate or improper screw fixation, malpositioned plates or screws, poor plate contouring, and failure to use cancellous bone grafts when a gap is present at the fracture site. A thorough understanding of the principles of plate and screw application helps to avoid most problems. The surgeon must use an implant that will stabilize the fracture adequately during the healing process. The patient's activity levels must not exceed the mechanical limits of the implant. Methods to promote bone healing, such as using cancellous bone grafts when a deficit is present, help to protect the implant from fatiguing before the fracture is healed. Proper positioning and contouring of the implants are important to the successful application of plates and screws. It must be realized that even if all of these things are done, some complications still will occur. When that happens, the complication should be dealt within a manner that will allow the objectives of fracture treatment (a healed bone and normal limb function) to be achieved. PMID- 1897081 TI - Complications associated with the use of Steinmann intramedullary pins and cerclage wires for fixation of long-bone fractures. AB - There is a unique clinical situation created with each fracture. The veterinarian must be able to synthesize an acceptable method of treatment based on the patient, the owner, and the particular fracture with which he or she is confronted. Stable fixation and preservation of blood supply are prerequisites to successful osteosynthesis. Careful consideration of the fracture type and its location will provide an insight to the type and magnitude of forces that caused the fracture and which might disrupt fixation. Understanding the strengths and weaknesses of the particular implant and adhering to the principles of use will limit the number of complication that occur. Proper application of the implant is of utmost importance. PMID- 1897082 TI - Complications of external fixation. A problem-oriented approach. AB - External fixation is an effective method of stabilizing many fractures in veterinary orthopedics, however, it is not foolproof. Although careful attention to the principles of fixator selection and application is the optimal way to minimize complications, they do still occur. Prompt recognition of these complications and appropriate treatment, however, will minimize their effects and result in the successful outcome of fracture healing and normal limb function. PMID- 1897083 TI - Complications of fractures repaired with casts and splints. AB - Complications of external coaptation of fractures include delayed and nonunion healing from lack of adequate fracture stability, pressure and rub sores, leg swelling, dermatitis, joint laxity or stiffness, cast or splint breakage, and refracture. Most of the complications are a result of improper application of the coaptation device or poor management of the patient. Early recognition and treatment of complications are needed to minimize their effect. The number of complications resulting from external coaptation can be minimized by proper application of the cast or splint. PMID- 1897084 TI - Delayed unions and nonunions. Diagnosis, pathophysiology, and treatment. AB - This article describes the different situations that result in interference with fracture healing and discusses the possible causes of such problems. Prevention and treatment of these states are reviewed. PMID- 1897085 TI - Malunions. AB - The decision to attempt surgical correction of a malunion must be based on a careful preoperative assessment of the patient. The animal's gait must be observed. An animal that is not clinically affected by the malunion usually is not a candidate for surgery. Joint function and the condition of the bone, cartilage, and soft tissues must be noted. If the joints and soft tissues are irreversibly altered, surgical correction should not be performed. Accurate planning of any corrective osteotomy requires careful evaluation of the bony deformities that are present. Angular and rotational deformities may be present. Shortening of the limb also may be observed. Integration of these findings enables the surgeon to select the osteotomy technique best suited for a patient. External fixators or bone plates are most commonly used to stabilize the corrective osteotomy. When contemplating surgical correction of a malunion, critical preoperative assessment and planning are essential to achieving the desired goals. These goals are achieving normal limb function and preventing further damage to the joints of the limb. PMID- 1897086 TI - Posttraumatic osteomyelitis. AB - Posttraumatic osteomyelitis is the most common type of osteomyelitis in the dog and cat. Poor surgical technique is the leading cause of this disease. Its pathogenesis involves the interaction of an infected wound, avascular bone, and favorable milieu. Treatment usually involves surgery; the goal is to improve the environment. Because treatment is not totally successful and is lengthy and costly, the main emphasis in dealing with this disease should revolve around its prevention. PMID- 1897087 TI - Morphology of fracture nonunion and osteomyelitis. AB - The author reviews the types and pathogenesis of fractures that fail to heal. A discussion of acute osteomyelitis and the causes of hematogenous disease is included. Classifications of osteomyelitis and idiopathic bone inflammations are described. PMID- 1897088 TI - Fracture disease and related contractures. AB - Fracture disease and the complications of immobilization are described. The pathogenesis of the disease is discussed. The clinical implications of immobilization are outlined, and physical therapy modalities are reviewed. Also included is a summary of quadriceps contracture management. PMID- 1897089 TI - Fracture-associated sarcomas. AB - Fracture-associated sarcomas occur at the site of a fracture that usually occurred 5 or more years ago. This article reviews hypotheses regarding the casualty of these sarcomas. Diagnosis and treatment are described, and ways to avoid development of fracture-associated sarcomas are discussed. At present, the best treatment is prevention, and the best mode of prevention is to achieve uncomplicated fracture healing. PMID- 1897090 TI - Environmental factors affecting the severity of pneumonia in pigs. AB - The variable manifestations of respiratory problems in finishing pigs have led to the concept of a multiple-factor aetiology for swine respiratory disease and in particular for enzootic pneumonia. The primary and secondary agents of the disease produce their most detrimental economic effects and the highest levels of mortality and morbidity during the finishing period, when the economics of production necessitate indoor housing and intensification. This paper considers the contribution of four main groups of environmental factors to the high levels of clinical disease and lesions which are found whenever large numbers of pigs are examined at slaughter. They are meteorological factors, population and social factors, management factors and airborne pollution. PMID- 1897092 TI - Vets and fish. PMID- 1897091 TI - Investigations into the use of exogenous oxytocin for promoting uterine drainage in mares susceptible to endometritis. PMID- 1897093 TI - Myotonia in two aged poodles. PMID- 1897094 TI - PCR test for Chlamydia psittaci. PMID- 1897095 TI - Pieris poisoning in sheep. PMID- 1897096 TI - Surgical treatment of open splint bone fractures in 26 horses. AB - Over a period of 16 years, 26 horses were treated for open fractures involving the splint bones. Treatment consisted of surgical excision of fracture fragments and sequestra, and curettage of infected and unhealthy tissues. The splint bone distal to the fracture was removed in nine horses in which the attachment of the splint bone to the cannon bone via the interosseous ligament did not provide adequate stability. In two horses it was considered necessary to stabilise the proximal fragment by internal fixation and infection developed in both of them; one of these horses was destroyed on humane grounds. In the other 25 horses an excellent result was obtained in terms of cosmetic appearance and return to soundness. PMID- 1897097 TI - The lack of effect of parvovirus vaccination on the seminal characteristics of dogs. AB - The onset of ejaculation and development of normal seminal characteristics in six young dogs vaccinated and seroconverting against canine parvovirus did not differ from the accepted range, and by 45 weeks of age the ejaculates were considered to be normal. At one year of age three of the dogs were given a large antigenic stimulus by vaccination once a week for four weeks; this produced no change in the output or characteristics of spermatozoa. PMID- 1897098 TI - Benzimidazole resistance in equine strongyles: association with clinical disease. PMID- 1897099 TI - 'Blue ear' disease of pigs. PMID- 1897100 TI - Photosensitisation in foxhounds. PMID- 1897101 TI - Wing tip oedema and dry gangrene in birds. PMID- 1897103 TI - Chronic glaucoma in cairn terriers. PMID- 1897102 TI - Benzimidazole resistance in sheep nematodes. PMID- 1897104 TI - Treatment of adder bites. PMID- 1897105 TI - 'Point source' haemorrhages in cows. PMID- 1897106 TI - Early abortion in cattle induced by experimental intrauterine infection with pure cultures of Actinomyces pyogenes. AB - Actinomyces pyogenes from a case of endometritis was used to study the effects of infection of the bovine embryo between days 27 and 41 of pregnancy. From 10(9) to 10(10) washed organisms were introduced into the uterine lumen of four pregnant cows. Two pregnant cows were inoculated with sterile saline and four pregnant cows were treated with cloprostenol. Embryonic death and abortion followed 29 to 144 hours after the inoculation of the live bacteria. The aborted embryos were macerated or clearly degenerating and yielded profuse pure cultures of A pyogenes. Abortion was accompanied by a sustained increase in uterine tone, opening of the cervix, presence of vaginal pus and a vulval discharge and the persistence of the corpus luteum for at least eight days after abortion. Intrauterine inoculation with saline did not affect pregnancy, but embryonic death, abortion and regression of the corpus luteum occurred 66 to 72 hours after the treatment with cloprostenol. The results suggest that A pyogenes is a primary pathogen and is capable of causing embryonic death and abortion. PMID- 1897107 TI - Fallen stock. PMID- 1897108 TI - Nematodirus species on St Kilda. PMID- 1897109 TI - Use of human influenza vaccine to protect against blue-eared pig disease. PMID- 1897110 TI - Cryptosporidium muris in cattle. PMID- 1897111 TI - Tuberculosis in deer: a review. AB - In recent years tuberculosis in deer caused by Mycobacterium bovis has become a disease of economic as well as public health importance to the deer farming industries of several countries, in particular those in Denmark, New Zealand and the United Kingdom. This paper sets the disease in a historical context and reviews current knowledge about various aspects of the condition, with particular reference to diagnosis and control and to research requirements for the future. PMID- 1897112 TI - Age resistance in calves to Ostertagia ostertagi and Cooperia oncophora. AB - Calves were infected repeatedly during a period of 6 weeks with Ostertagia ostertagi and Cooperia oncophora, at an age of 3, 6 or 9 months. The inoculations were performed during three periods, February-March, May-June and August September, to account for possible seasonal effects or effects of larval batches. Observations were done on faecal egg output, antibody titres and weight gains. Calves were slaughtered for post mortem examinations 9 weeks after the start of infections. The influence of age on worm populations and egg output was significant for C. oncophora but not for O. ostertagi. The effect of season or larval batch on worm populations was significant for O. ostertagi but not for C. oncophora. The correlations between worm numbers and several other parameters found for Cooperia were strongly indicative of a process of worm expulsion taking place at the stage of infection (9 weeks after the start of infections) when post mortem examinations were done. Such correlations were absent for Ostertagia. It is concluded that within the range of ages examined here (the range to which first season grazing calves belong), there is no influence of age on Ostertagia populations but a clear effect of age on Cooperia. This difference strongly influences the total faecal egg output of grazing calves and its interpretation. PMID- 1897113 TI - Accuracy of two methods for counting eggs of sheep nematode parasites. AB - A comparative study was carried out on eight species of sheep gastrointestinal nematodes in order to compare the value of two techniques for egg counting: the classical McMaster technique with saturated magnesium sulfate solution and a technique of egg extraction from faeces and counting by total collection after three centrifugations. Efficiency of extraction from 10 g of faeces was 95.9 to 99.5% according to the species of parasite, whereas the number of eggs counted by the McMaster technique represented only 16.5% of the total eggs present in the faeces. Advantages inherent in the use of these techniques are discussed. PMID- 1897114 TI - Effect of parasitism with Nematodirus battus on the pharmacokinetics of levamisole, ivermectin and netobimin. AB - The pharmacokinetics of levamisole, ivermectin and netobimin administered orally and by subcutaneous injection were compared in lambs exposed to a moderate challenge with Nematodirus battus and in parasite naive lambs. There were no significant differences (P greater than 0.05) in the bioavailability of any of the anthelmintics tested between parasitized and non-parasitized animals. Levamisole reduced nematode faecal egg output by more than 99% when administered by either route. Ivermectin was also highly effective (greater than 99%). Orally administered netobimin reduced egg output by more than 98% seven days after administration. However egg output was only reduced by 89% 21 days after administration, suggesting poor activity against the early parasitic stages of N. battus. Netobimin was not effective against N. battus when administered by the subcutaneous route and this was probably because very low plasma concentrations of its active albendazole metabolites were achieved. PMID- 1897115 TI - Effect of isometamidium on Trypanosoma congolense infectivity. AB - Isometamidium chloride (Samorin, RMB, England) is a widely used and highly effective trypanocide for the treatment of bovine trypanosomiases. However, the appearance of isometamidium-resistant populations of T. congolense in Africa makes it necessary to develop methods for the rapid and reliable detection of drug resistance in the laboratory. Currently available tests are time-consuming and/or expensive. In the present study, the short-term in vitro incubation of trypanosomes in a range of isometamidium concentrations and the infectivity of the parasites in mice has been assessed. A series of T. congolense isolates were used which were known to differ in their in vivo sensitivity to the drug. The results showed a close correlation between the known level of resistance and the capability of trypanosomes to remain infective after incubation in isometamidium. Thus isolates displaying a high level of resistance in vivo remained infective following incubation in higher concentrations of drug. This assay may provide a simple and reliable method for detecting drug resistance in T. congolense. PMID- 1897116 TI - Use of pooled serum or milk samples for the epidemiological surveillance of bovine hypodermosis. AB - An enzyme-linked immunosorbent assay (ELISA) was used on pooled serum and milk samples to determine whether hypodermosis could be detected where a larger sero epidemiological survey was required. This study was undertaken to assess the potential of this assay for testing sera on milk samples, pooled from 10 cows, and determining the period of the year when detection was optimal. The sensitivity of the assay was determined by increasingly diluting a positive serum with pooled negative sera, from 1:10 to 1:100. The diagnostic lower limit of the assay requires at least two serological reactors within a herd of 100. The kinetic development and depletion of anti-Hypoderma antibody of individual and pooled sera or milk from 30 cows was evaluated from November to July. Anti Hypoderma antibody levels of two groups of 8 calves, one control and one teated with ivermectin (Ivomec), were tested from October to June. These preliminary results indicate that an ELISA assay on serum or milk samples pooled from 10 cows can be used between February and April to evaluate the prevalence of hypodermosis within cattle herds in France, demonstrating the feasibility of using pooled serum already collected for bovine leucosis testing. PMID- 1897117 TI - Detection of Babesia equi in infected horses and carrier animals using a DNA probe. AB - The ability of the Babesia equi repetitive probes, pSE2 and pSB20, to detect parasites in blood from experimentally infected, naturally infected and carrier animals was tested using a spot hybridization assay. The clinical course of the experimentally infected horses was monitored using microscopy, indirect fluorescent antibody tests, packed cell volume, temperature and the probe assay. The probes sensitively monitored the parasite level during the development of the disease and correlated well with the other parameters tested. The sensitivity of the probe assay was superior to that of light microscopy, and a parasitaemia equivalent to less than 0.0025% could be detected. Detection of B. equi DNA was possible in all natural cases tested and 20 of the 119 randomly selected horses were identified as carriers of B. equi parasites. Microscopy could identify parasites in only 8 of these carrier animals. These results show that the probes can detect B. equi parasites in carrier animals and that they are suitable for use in a laboratory-based assay for B. equi. PMID- 1897118 TI - Therapeutic effect of Berenil and Samorin in mice infected with four trypanosome populations isolated from Zambian cattle. AB - Four populations of Trypanosoma congolense and Trypanosoma brucei brucei were isolated from cattle under different management practices and environments in Zambia. All four isolates had varied responses to both diminazene aceturate (Berenil) and isometamidium chloride (Samorin) as curative drugs in infected mice. Trypanosomes from a traditionally managed herd in a high-tsetse-challenge area had the strains most resistant to Berenil, with maximum curative dose of 45 mg kg-1 body weight. Another isolate from a high-tsetse-challenge area was evidently resistant both to Berenil at 40 mg kg-1 and to Samorin at 4 mg kg-1. The strains most susceptible to both Berenil and Samorin were from a commercially managed herd of cattle under medium tsetse challenge. They responded to recommended cattle standard doses of 3.5 mg kg-1 or 7 mg kg-1 Berenil and to as little as 0.25 mg kg-1 Samorin. It is evident that trypanosome strains resistant to Berenil and/or partially resistant to Samorin exist, and that both T. congolense and T. b. brucei are implicated. PMID- 1897119 TI - Pathophysiological studies on Dicrocoelium dendriticum infection in sheep. AB - Red cell kinetics and plasma protein metabolism were investigated in two experiments using 20 adult sheep naturally infected with Dicrocoelium dendriticum, but free of other liver and gastrointestinal helminths. In the first experiment, where groups of animals with low to high Dicrocoelium burdens were injected with 51Cr-labelled red cells and 125I-labelled albumin, the results indicated that there were no significant differences in the turnover rate of labelled red cells or albumin between any of the groups. In the second experiment, two groups of sheep with low and high worm burdens were studied using the same radioisotope tracers; in addition, 59Fe-citrate was used to assess red cell iron incorporation rates in the two groups. Although the red cell half-lives of the infected sheep were just significantly longer, both were within normal limits and the difference was attributed to random variation within the two small groups of sheep. No significant differences were found in the other parameters. It was concluded that burdens of up to 4000 D. dendriticum do not cause significant blood or plasma protein loss in sheep. PMID- 1897120 TI - Onchocerca fasciata Railliet and Henry, 1910 and its nodule development in camels in Saudi Arabia. AB - A total of 192 male camels of three age groups (young, adult and old) from Saudi Arabia were examined for Onchocerca fasciata infection by detection of microfilariae in skin snips and nodules in the nuchal ligaments and subcutaneous tissues of the neck and shoulder. The overall prevalence rates were 10.9 and 33.3%, respectively. The prevalence rate by the skin snip technique and the number of microfilariae per gram of skin were higher in young and adult camels than in old camels. However, the prevalence rate by the detection of nodules and the number of nodules per infected camel, increased with increase in age of the camels. An increase in size and weight of nodules was reported with an increase in age of the camels. Nodules varied in diameter from 2 to 36 mm and in weight from 0.5 to 5.0 g. The overall percentage of soft viable and calcified nodules was 42.5 and 57.5%, respectively. The viability of worms decreased, but calcification increased with increased age of the camels. Four levels of degeneration and calcification of worms were described following scanning electron microscopy. PMID- 1897121 TI - Periparturient rise in faecal nematode egg counts in west African dwarf sheep in southern Ghana in the absence of arrested strongyle larvae. AB - The nematode egg output of two groups of ewes, a pregnant test group (2-3 years of age) mated between March and April and a non-pregnant control group (5-6 years of age) was followed. The worm burdens acquired by worm-free 'tracer' lambs were also followed on the same pasture from March 1988 to February 1989. There was a significant difference (P less than 0.05) in the magnitude of the egg output in the test group compared with the control group. In the test ewes, an initial rise in egg production occurred 2 weeks after lambing and was maintained for five consecutive months. Necropsy worm counts from the 'tracer' lambs revealed that pasture larval levels were directly related to the levels of rainfall. Adult nematodes (Trichostrongylus colubriformis, Trichostrongylus axei, Haemonchus contortus, Oesophagostomum venulosum and Trichuris ovis), and some Moniezia expansa were present in almost all the lambs throughout the year, with the exception of January and February 1989. The absence of immature larvae in these lambs indicates that arrested development is not a feature of the life cycle of these species in Southern Ghana. The occurrence of a periparturient rise of nematode eggs in West African Dwarf ewes, a year-round breeder, means that susceptible lambs could be open to infection throughout the year. Control should, therefore, be conducted by treating ewes after lambing and restricting the breeding season to particular periods of the year. PMID- 1897122 TI - Preliminary characterization and interaction of tubulin from Trichinella spiralis larvae with benzimidazole derivatives. AB - Tubulin was estimated to account for 0.3% of the total soluble protein in Trichinella spiralis cytosolic fractions. Tubulin from T. spiralis was partially purified by precipitation with either taxol or vinblastine sulphate. Immunoblotting with alpha- and beta-tubulin monoclonal antibodies revealed the presence of tubulin in T. spiralis partially purified preparations. Electrophoretic mobility of T. spiralis tubulin in sodium dodecyl sulphate polyacrylamide gels was very similar to that shown by pig brain tubulin. Further studies with colchicine binding assays indicated that T. spiralis tubulin has binding features similar to that of tubulin from other nematodes: colchicine association constant = 8.1 x 10(-4) M and competitive inhibition of colchicine binding by podophyllotoxin, with an inhibition constant of 1.3 x 10(-6) M. Finally, inhibition of colchicine binding by several benzimidazoles (mebendazole, fenbendazole, oxibendazole and albendazole) was investigated. All the benzimidazoles inhibited colchicine binding in a competitive manner, with inhibition constant values ranging from 1.4 x 10(-7) M (mebendazole) to 3.9 x 10( 6) M (fenbendazole). PMID- 1897123 TI - Differentiation of naphthalene and paradichlorobenzene mothballs based on their difference in specific gravity. AB - The present study was conducted to measure the specific gravities of paradichlorobenzene and naphthalene mothballs and compare them with the specific gravity of a saturated aqueous solution of sodium chloride (1.197). The specific gravities of 450 paradichlorobenzene mothballs from 5 manufactures and 150 naphthalene mothballs from 2 manufactures were measured with a specific gravity meter. The mean specific gravities of paradichlorobenzene mothballs were between 1.429 and 1.437 (p = 0.99). On the other hand, the mean specific gravities of naphthalene mothballs were between 1.094 and 1.100 (p = 0.99). Based on the fact that paradichlorobenzene mothballs sink in a saturated solution of salt whereas naphthalene mothballs float on it, these 2 kinds of mothballs ought to be rapidly and accurately distinguished in clinical settings. PMID- 1897124 TI - Pyrethroid insecticides and pregnancy: effect on physical and behavioral development of rats. AB - We investigated the prenatal effects of cyhalothrin exposure on the physical and behavioral development of infant and adult rats. Female rats were treated by dermal exposure with a 0.018% cyhalothrin aqueous solution (1 ml/d) or the cyhalothrin vehicle during their entire pregnancy. The pesticide delayed development of fur, the ear and eye openings and descent of the testes in the offspring. The exploratory behavior of the rats prenatally exposed to cyhalothrin decreased. No differences were observed between control and experimental animals in inhibitory avoidance tasks at 90 d of age in open field activity. Alterations in physical parameters and possible effects of the pesticide on epidermal growth factor and hormonal levels were considered. Since no overt of signs of maternal or neonatal toxicity were observed, the decrease in adult motivational behavior was attributed to a specific effect of the pesticide administered during the prenatal period. We concluded that prenatal cyhalothrin exposure induced subtle and persistent changes in the physical development and behavior of rats. PMID- 1897125 TI - The frequency of spontaneously-occurring neoplasms in the male Syrian golden hamster. AB - The frequency of spontaneously-occurring neoplasms in the male Syrian golden hamster, often used as a control in carcinogenic studies, was examined. The hamsters were divided into 2 groups: Group 1 received 0.1 ml of the phosphate buffer vehicle intratracheally once a week for 15 w; Group 2 received 0.1 ml of Tween 60:ethanol:buffer (5.3:8.7:100 by volume) in the same manner. The mean survival days of hamsters' total life-span were 574.9 +/- 176.1 d in Group 1 and 427.7 +/- 178.1 d in Group 2. Tumor incidence rates were 10.6% (16/148) in Group 1 and 11.5% (13/113) in Group 2. The mean survival days for tumor-bearing hamsters in Group 1 was 692.0 +/- 80.7 d and was 650.8 +/- 74.2 d in Group 2. Most tumors increased with advancing hamster age. The most common neoplasm was adrenal gland tumors (Group 1 = 4.7%, Group 2 = 8.8%). The occurrence of other tumors in other organs was low. The Syrian golden hamster is a suitable animal model for evaluating chemical carcinogenicity. PMID- 1897126 TI - Possible biotransformation mechanism of 3-aminopropionitrile by means of free radicals. AB - The possible role of free radicals in the transformation of 3-aminopropionitrile giving rise to the liberation of cyanide was studied. Rat liver homogenates were cellularly fractionated. It was confirmed that the transformation occurred mainly in the microsomal fraction. The different isozyme forms of cytochrome P-450 were then partially purified and their velocity and affinity constants determined. It could be deduced that the cyanide-forming activity was mainly due to the LM3C cytochrome form. Dimethylsulfoxide was a potent competitive transformation inhibitor while mannitol was a moderate one. An OH radical generator inorganic system was also shown to liberate cyanide from 3-aminopropionitrile. In view of these results, a transformation mechanism of 3-aminopropionitrile by means of OH free radicals is suggested with the formation of cyanide anion in a cell-free organic system as well as in the microsomal fraction of rat liver. PMID- 1897127 TI - Acute toxicity of taxine in mice and rats. AB - The acute toxicity of taxine isolated from leaves of yew trees was determined in mice and rats. The drug was used as the sulphate salt. The following LD50 values (mg/kg) and 95% confidence limits were found: mice po 19.72 (16.84-23.09); mice ip 21.88 (19.66-24.35); rats sc 20.18 (18.35-22.20). PMID- 1897128 TI - A poison information service for small animals offered by a regional poison center. AB - Since 1985 the Hennepin Regional Poison Center has provided the same quality service to veterinarians and pet owners that parents of small children, physicians and other health care providers have enjoyed for many years. To facilitate this service, the poison center has expanded its data base to include information on small animal poisonings and has periodically mailed newsletters state-wide to veterinarians. In addition, the poison center began to routinely assist per owners in the home treatment of minor ingestions in dogs, and enlisted the aid of a veterinary toxicologist who is on-call for consultation. Prior to 1985, animal-related exposures totaled 1,092 cases, which comprised 3.9% of the center's total annual cell volume. As a result of the above efforts, calls from veterinarians and pet owners increased to approximately 2,000 cases annually for the period 1986-88 (average 6.3%). Recently, the poison center received the financial support of the Minnesota State Veterinary Association for the printing of telephone stickers promoting a line exclusively for pet calls (337-PETS). This Pet Poison Information Service appears well received, resulting in an additional 58% increase in pet-related calls. During 1990 this center consulted on over 3,500 exposures in companion animals. Based on our experience, veterinarians and pet owners appear to have been relatively neglected by poison centers. Poison centers may play an important role in the treatment of poisonings in pets. PMID- 1897129 TI - Granuloma formation induced by spines of the cactus, Opuntia acanthocarpa. AB - Embedded cactus spines may cause immediate pain due to mechanical damage, be a source of infection, or result in foreign body granulomas. The cholla cacti are particularly tenacious in the manner in which the spines stay embedded in the skin. Pulling away from the cactus may result in a portion breaking away from the main plant and embedding other spines. Granuloma formation has been seen with plant material embedded in the dermis. Onset is generally within a few days, and duration may be as long as 9 mo. Treatment is generally best accomplished with a topical corticosteroid. We present a case of granuloma caused by the cactus Opuntia acanthocarpa which persisted for 8 w despite topical treatment with 0.05% fluocinonide. PMID- 1897130 TI - Nitrite intoxication from large round bales. PMID- 1897131 TI - Recovery of a herpesvirus from a roan antelope (Hippotragus equinus). AB - A herpesvirus was recovered in culture from the cells of a roan antelope (Hippotragus equinus) following cryopreservation in DMSO and it is thought that the DMSO may have been involved in reactivation. The virus was shown to be antigenically related to alcelaphine herpesvirus-1 (AHV-1) of wildebeest and ovine herpesvirus-2 (OHV-2) of domestic sheep (formerly designated the sheep associated agent of malignant catarrhal fever (MCF]. Cloned DNA fragments of AHV 1 and OHV-2 cross hybridised with DNA prepared from cells infected with the roan antelope virus and the intensity of reaction suggested that this virus was more closely related to AHV-1 than is OHV-2. The virus represents the third gamma herpesvirus isolated from large African antelope and should be provisionally designated hippotragine herpesvirus-1. On inoculation into rabbits the virus induced malignant catarrhal fever indicating that roan antelope should be considered as a possible source of infection. PMID- 1897132 TI - Inhibitory effects of fibrinogen on phagocytic killing of streptococcal isolates from humans, cattle and horses. AB - The effects of fibrinogen on phagocytic killing of Streptococcus dysgalactiae from cattle and S. equi from horses were studied in comparison to that of S. pyogenes from humans. Phagocytic killing was determined by a fluorometric microassay using glass adherent polymorphonuclear neutrophils (PMN) from the respective host species, preopsonization with homologous sera led to a dose dependent increase in phagocytic killing of all streptococcal cultures, preincubation of streptococci with fibrinogen significantly inhibited their phagocytic killing. Fibrinogen had no effect on phagocytic killing of non fibrinogen binding S. agalactiae cultures. Further characterization studies with S. dysgalactiae and S. pyogenes revealed that a partial inhibition of phagocytic killing could also be achieved by preincubation with monomeric beta-chains of fibrinogen. Digestion of the fibrinogen binding sites on streptococci with proteases resulted in an almost complete loss of the inhibitory effects of fibrinogen on phagocytic killing. It could thus be concluded that by binding fibrinogen animal pathogenic streptococci could evade phagocytic killing in a similar manner as M protein carrying S. pyogenes isolates from human infections. PMID- 1897133 TI - Identification and partial characterization of the hemolysin (HlyII) of Actinobacillus pleuropneumoniae serotype 2. AB - The secreted hemolytic activity produced by Actinobacillus pleuropneumoniae serotype 2 reference strain is thermolabile, inactivated by proteinase K and requires Ca2+ as cofactor for its hemolytic activity. Purification of the hemolytic activity resulted in a fraction containing two proteins, one of 105 kDa and one of 125 kDa. These two proteins could be further separated by preparative SDS polyacrylamide gel electrophoresis. This purification step, resulted in loss of the hemolytic activity. Polyclonal antibodies were made against each of these proteins in rabbits. Neutralization experiments showed that antibodies made against the 105 kDa protein could neutralize the hemolytic activity produced by A. pleuropneumoniae serotype 2, while antibodies made against the 125 kDa protein were unable to neutralize the hemolytic activity. The 105 kDa protein therefore, is the hemolysin of A. pleuropneumoniae serotype 2, known as HlyII. This protein is closely related immunologically to the hemolysin I (HlyI) from A. pleuropneumoniae serotype 1. DNA::DNA hybridization experiments performed by the Southern blot method using the cloned structural gene of HlyI from A. pleuropneumoniae serotype 1 demonstrate that the structural genes of the two hemolysins (hlyIA and hlyIIA) are different and show at least 30% heterology. This confirms that HlyI and HlyII are two different proteins, although they have a very similar molecular weight and show strong immunological cross reactions. PMID- 1897134 TI - An Anaplasma centrale DNA probe that differentiates between Anaplasma ovis and Anaplasma marginale DNA. AB - An Anaplasma centrale genomic library was constructed in pUC13. Two clones pAC5 and pAC137 hybridising to A. centrale and A. marginale DNA were isolated from this library. One of these, pAC5, also hybridised to DNA from A. ovis. The total insert of pAC5 was subcloned into pBR322. This subclone, pAC5-12, could detect 1 ng A. centrale, 0.5 ng A. marginale and 3.9 ng A. ovis DNA. The hybridisation pattern obtained with pAC5-12 on digests of A. centrale, A. marginale and A. ovis DNA suggests that this probe detects EcoR1 and Hind111-polymorphisms. Probe pAC5 12 could detect A. ovis DNA in 36% of blood samples tested compared to the 33% detectability obtained with microscopy. PMID- 1897135 TI - [Autoimmune mechanisms in endocrinology--the polyglandular autoimmune endocrine syndrome]. AB - Autoimmune endocrinopathies belong to so-called organ specific autoimmune diseases. These diseases combine very often and from the polyglandular autoimmune endocrine syndrome (PAES), where autoantibodies either destroy or stimulate individual endocrine glands or hormone receptors in target tissues. Thus a wide range of combinations of hypofunctional or hyperfunctional clinical syndromes develops. PAES is a good natural model of endocrine polyautoaggressiveness. In its development the following aetiopathogenetic factors participate: 1. Hereditary familial disposition, expressed e.g. by certain inherited HHS genes (e.g. A1, B8, DR 3, 4). 2. Aberrant expression of these DR genes on endocrine organs due to bacterial or viral infections, pregnancy, stimulation of the thyroid gland by TSH or immunoglobulins (TSIg). 3. Antigenic mimicri and the presentation of autoantigens to immunocompetent cells. 4. Impaired immunoregulation--antigen specific insufficiency of suppressor T lymphocytes. 5. Local and general amplification reaction to an autoimmune process. 6. The development and autoreproduction of organ specific autoimmune endocrine disease and its development into the final stage of endocrine disease where autoantibodies may disappear. The diagnosis of PAES in clinical practice is difficult. Common immunological tests are not very conclusive. To assess a polyglandular affection we found useful the multiaxial synchronous test where stimulation of several hypothalamic releasing hormones combined with a hypoglycaemic stimulus is used. Autoimmune lymphocytic hypophysitis is part of PAES. In clinical practice this syndrome is therefore frequently incorrectly diagnosed and then incorrectly treated. PMID- 1897136 TI - [The effect of hemodialysis on potassium excretion by residual nephrons]. AB - In 19 patients with chronic renal failure and still preserved residual diuresis the inulin clearance (Cin) and renal potassium excretion were assessed before and 12 hours after haemodialysis (HD), combined with conventional ultrafiltration. The mean value of Cin after HD declined significantly (p less than 0.001). As a result of HD a significant decline of the plasma potassium concentration occurred (p less than 0.005) and of the urinary excretion (p less than 0.01). The mean value of the fractional potassium excretion (FEK) did not change significantly as a result of HD. The reduced urinary K excretion after HD correlated significantly (p less than 0.05) with the decline of Cin. The findings suggest that the decline of the urinary potassium excretion after HD is above all due to a decline of the glomerular filtration rate. The tubular potassium secretion does not change significantly under these conditions. These findings support indirectly the idea that the increased tubular potassium secretion in residual nephrons in patients with chronic renal failure is not conditioned by retention of low-molecular dialysable substances. PMID- 1897137 TI - [Determination of quantitative proteinuria from a single urine sample based on the protein:creatinine ratio]. AB - Assessment of quantitative proteinuria is associated with collection of urine over several hours. This is, however, not always possible, in particular in ambulatory patients. Therefore efforts are made to assess the urinary protein per 24 hours on the basis of the proteinuria index, i.e. the ratio protein:creatinine in a single urine specimen. In a group of forty patients the authors demonstrated the closest correlation (correlation coefficient = 0.910374) between quantitative proteinuria and the index of proteinuria in urine specimens which were collected during daily activity. The closeness of this correlation depends on renal function. Assessment of quantitative proteinuria from a single urine sample on the basis of the protein:creatinine ratio is therefore useful in subjects with a preserved or not very restricted renal function. PMID- 1897138 TI - [Diagnosis of diabetes mellitus based on the renal biopsy]. AB - In a total of 1499 representative renal biopsies 30 displayed morphological changes suggesting diabetic nephropathy. Six patients had clinically diagnosed diabetes at the time of biopsy, 20 according to the bioptic finding, and in four patients the examination did not confirm diabetes. The authors describe the morphological vascular changes in particular the cumulation of masses resembling the mesangial matrix and basal membranes, as well as hyaline lesions, their development, site and combinations. In the author's opinion the most reliable sign of early diabetic nephropathy is thickening of the glomerular basal membrane. They draw attention to the non-specific character of the morphological finding and the necessity to diagnose diabetes mellitus by clinical and in particular by laboratory methods. PMID- 1897139 TI - [Increased numbers of large granular lymphocytes in the peripheral blood in selected inflammatory rheumatic diseases]. AB - In six patients with selected inflammatory rheumatic diseases the authors found increased numbers of LGL in the peripheral blood. Concurrently in these patients an increase of lymphocytes with the CD57 sign was found. In one patient with rheumatoid arthritis more detailed analysis revealed a reduced number of lymphocytes with sign CD16. In this patient in the peripheral blood cells with signs CD3+ and CD57 were found and the function of NK cells was markedly reduced. The clinical course of the disease in the patients was severe, in particular in SLE, where in three patients the disease was associated with the development of lupus glomerulonephritis. The patients were treated by immunosuppressive therapy. The authors reflect on the causes of the increase of LGL cells and do not rule out the possible presence of a serious immunoregulatory disorder between T and B lymphocytes. PMID- 1897140 TI - [The validity of laboratory tests in the diagnosis of alcoholism and alcoholic liver injury]. AB - The authors assessed the value of commonly available laboratory examinations for the diagnosis of suspected excessive alcohol intake and suspected liver damage by alcohol. They tested the validity of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gammaglutamyl transferase (GMT), the blood sugar level, serum cholesterol, bilirubinaemia, ferrinaemia and mean corpuscular volume (MCV). The highest validity as regards sensitivity of the examination was recorded in the MCV with a sensitivity of 0.78 and examination of GMT with a sensitivity of 0.72. By combination of MCV and GMT in an alternative manner, the sensitivity rose to 0.87. Evaluation of the groups by the method of discrimination analysis, using all ten parameters, revealed the possibility of 100% correct classification of non-alcoholic subjects and a 86.2% correct qualification of alcoholic subjects. PMID- 1897141 TI - [Analysis of the use of gentamicin, cotrimoxazole and cephalosporin in selected hospitals]. AB - The authors investigated the administration of monitored antibiotics, i.e. gentamicin, cephalosporins and cotrimoxazol, as well as of other so-called not monitored antibiotics. The investigation was made in the same 10 hospitals in the Slovak Republic three times in the course of 15 years, i.e. in 1978, 1983 and for the last time in 1988. It was revealed that the number of therapeutic administrations of the monitored antibacterial substances in increasing. The excessive gentamicin administration persists in particular on neonatal, premature infant and surgical departments. The authors evaluate as a positive feature that the structure of administered antibiotics changes, i.e. the amount of gentamicin administration is declining and the cephalosporin administration has a rising trend. The investigated antibiotics were administered for an average period of 10.6 days which is too long, in particular in gentamicin where the period was as long as 9.2 days. The investigated antibiotics were administered most frequently in diseases of the airways and in diseases of the urinary and genital system. PMID- 1897142 TI - [Renin and aldosterone in the first 24 hours after acute myocardial infarct]. AB - The authors investigated the levels of plasma renin activity and aldosterone in patients with a fresh myocardial infarction during the first 24 hours of hospitalization. The values of plasma renin activity and aldosterone were correlated with values of the control group. At the time of admission to the clinic both hormones were significantly elevated, as compared with the control group, in plasma renin activity p less than 0.001 and in aldosterone p less than 0.01. During the subsequent time intervals, i.e. after 3, 6 and 24 hours, the values of plasma renin activity did not change substantially, while the aldosterone values declined during the 6th and 24th hour (significance p less than 0.05). No significant relationship was found between plasma renin activity an aldosterone. With regard to persisting elevated values of plasma renin activity the authors discuss the possible use of blockers of the angiotensin converting enzyme in order to inhibit in the initial stage of a new infarction the formation of endogenous pressor substances. PMID- 1897143 TI - [Angiotensin-converting enzyme inhibitors in the diagnosis and treatment of kidney diseases]. AB - The authors describe in a review the use of inhibitors of the angiotensin converting enzyme, in particular enalapril, in the treatment of nephrogenic hypertension, glomerulopathies without hypertension, renovascular hypertension with unilateral or bilateral stenosis of the renal artery and diabetic nephropathy. They draw attention to specific traits in the treatment of different disorders, risk of treatment and the ensuing tactics of indication, dosage and monitoring. PMID- 1897144 TI - [Medicine in the life and work of Frantisek Hamza]. PMID- 1897145 TI - [Disaster medicine and the military medical aspect of the problem of shock]. PMID- 1897146 TI - [The organization of x-ray studies in the mass arrival of victims]. PMID- 1897147 TI - [The social sciences on the path of perestroika]. PMID- 1897148 TI - [The military orientation in teaching the students of a military medical faculty in the department of eye diseases]. PMID- 1897149 TI - [Experience in organizing the treatment of patients at the day hospital of a polyclinic]. PMID- 1897150 TI - [Work planning in the medical unit of a military sanatorium]. PMID- 1897151 TI - [The treatment of gunshot wounds of the hand]. AB - During the war in Afghanistan gunshot hand injuries came to 12% of all wounded among Soviet servicemen. At the stages of specialized medical care the vast wounds, crushes or amputations of hand were 49%, hand injuries accompanied by traumata of other anatomical zones were 42%. The gravity, concomitant and multiorgan character of the injuries required that the conservative and active methods of treatment, as well as the expert appreciation of that category of wounded should be developed and improved. Field surgeons frequently performed primary operations accompanied with the elements of the specialized medical care. The experience shows that the local purulent complications during the primary surgical management of wounds performed without elements of specialized medical care were up to 29,5%, and in primary reconstructive operations--12.4%. Osteomyelitis was correspondingly recorded at 11.1% and 3.2% of cases. The efficiency of treatment was growing when microsurgical technique was used. PMID- 1897152 TI - [The surgical treatment of an atherosclerotic lesion of the femoral and popliteal arteries]. PMID- 1897153 TI - [The importance of sublingual pharyngotomy in the surgical training of military otolaryngologists]. PMID- 1897155 TI - [The treatment of peptic ulcer]. PMID- 1897154 TI - [The diagnosis and treatment of rhinogenous intracranial complications]. AB - The article describes the cases of acute affections of accessory sinuses of nose complicated by toxic infectious oedema of cerebrum with hypertension syndrome. Intracranial complications were originated by decompensation of the local inflammatory process, and need urgent surgical management on accessory sinuses of nose and further conservative treatment. The author gives the differentiated diagnostics of rhinogenous intracranial complications and recommendations for surgical and complex medicinal treatment of such patients. PMID- 1897156 TI - [Recalling the war]. PMID- 1897157 TI - [The characteristics of the internal picture of the disease in patients with endogenous psychoses and peptic ulcer]. AB - The studies which were conducted at a group of patients with endogenic psychosis and ulcer of stomach or duodenum have shown that the internal course of ulcer diseases might camouflage for a long period the existence of mental illness that would negatively influence upon the treatment of such patients. In particular these are the cases of continuous sluggish schizophrenia and affective psychosis. All the patients with inadequate course of somatic illness need psychiatric consultation in order to prove the absence of mental illness and choose an adequate medical tactics. PMID- 1897158 TI - [The immunogenetic approach and the prinicples of forming an organized collective]. AB - The authors examine the mechanisms of connection between a great complex of human histocompatibility antigens and cellular and humoral factors of immunity that makes it possible to get the clearer idea about the reasons of individual susceptibility or, on the contrary, human stability to various diseases. Immunogenetic criteria cited in the article give the possibility to individualize the primary prophylaxis of illness. PMID- 1897159 TI - [Chronic pyococcal ulcer: treatment and prevention experience]. PMID- 1897160 TI - [The combined action on the body of ionizing and nonionizing electromagnetic radiations (a review of the literature)]. PMID- 1897161 TI - [A comparative assessment of the physical development of the students in a military college studying at the end of the 60s and the 80s]. PMID- 1897162 TI - [A clinico-physiological assessment of the basic nosological forms of eye pathology in pilots]. PMID- 1897163 TI - [The Party organization of the Main Military Medical Command of the Red Army in the third period of World War II (January 1944-May 1945)]. PMID- 1897164 TI - [Physiological changes in the blood leukocyte system of sailors]. AB - The complex appreciation of qualitative and quantitative changes in leukocyte blood system of sailors was performed. After short cruise there were moderate deviations of several hematological indexes that determine the dependency between quantity of leukocytes in peripheral blood and their functional characteristics. The biggest deviation of indexes, that testifies about metabolic changes comes to 9-14%, and immunobiological changes-up to 20-33%. After middle cruise the deviation comes to 15-23% (intracellular metabolism), and to 39-54% (immunobiological changes). After long cruise-up to 18-23% (intracellular metabolism) and 45-65% (immunobiological changes). The application of this methodical approach may widen the possibilities of the medical control over the health of sailors. PMID- 1897165 TI - [Current problems in the development of x-ray field technology]. PMID- 1897166 TI - [The use of membrane filtration in military pharmacies]. PMID- 1897167 TI - [Noise in helicopters and its effect on auditory damage in pilots]. AB - The effects of noise on hearing impairment was examined in 46 flyers in cabins of three types of helicopters. In spite of high values of the total noise level and its harmful effects in all the examined types of helicopters the statistically significant increase in hearing impairment was not found. Considering that flyers wear the helmet headphones for communication which in the same time protect them from harmful effects of environmental noise, hearing impairment was of a milder degree and of a smaller percentage. PMID- 1897168 TI - [The standard emotional profile index in a military population]. AB - Using the Emotional Profile Index (EPI), personality characteristics have been compared in two groups of examinees: one group of "adapted" and the another of "nonadapted" to life and work in the army. These data were also compared with data obtained using other standards and examinations. The EPI for "the adapted" was similar in all compared cases while the group of the "nonadapted" (emotionally immature) showed most similarities with a group of attempted suicide according to the study performed in the USA which enables better understanding of both groups. PMID- 1897169 TI - [Age distribution and clinical characteristics in acute appendicitis]. AB - The retrospective analysis comprised 986 of 1050 patients operated on for acute appendicitis in the period 1983-1987. Appendicitis was most common in the age group from 11 to 20 years. The perforation frequency was 12.4%. Seventy four percent of patients came to the first medical examination with already perforated appendix. The necessary period of observation is the first 12 hours after onset of troubles. Probable presence of phlegmonous appendicitis is small if 48 hours have passed after initiation of troubles. The frequency of the studied symptoms (nausea, vomiting, temperature, leukocytosis) ranged from 49.4% to 64.8%. The most common postoperative complication is wound infection. The overall mortality rate was 0.1%. PMID- 1897170 TI - [The role of radionuclide phlebography in the detection of deep venous thrombosis in the lower extremities and pelvis and in establishing indications for implantation of a caval filter]. AB - In all 40 patients with pulmonary thromboembolism (PTE) radionuclide phlebography (RNP) detected deep venous thrombosis (DVT), most commonly in the left iliac veins, in 20 (50%). RNP and contrast phlebography (CP) were performed in 18 patients and RNP sensitivity was found in 100% in all localizations of DVT and the largest specificity was obtained in the left side of the pelvis, in 92%. In 12 out of 18 patients cava filter was implanted and BNP specificity in the left upper leg reached 100% and in the right one 89.3%. In establishing indications for cava filter implantation RNP should be performed first so that by detecting embologenous TDV localizations the risk of jatrogenous PTE at cava filter implantation would be avoided or CF, if necessary. PMID- 1897172 TI - [The foveal avascular zone in nonproliferative diabetic retinopathy]. AB - The areas of the foveolar avascular zone (FAZ) were measured in the fluorescein angiograms and the comparison was made between 44 eyes of 22 diabetics with nonproliferative diabetic retinopathy and 32 eyes of the healthy nondiabetic controls. It was found that the area of the FAZ in diabetics ranged between a mean of 0.26 +/- 0.07 mm2 and in healthy nondiabetic controls 0.23 +/- 0.04 mm2 and it was statistically significant difference (p less than 0.05). The results obtained have shown that the area of the FAZ in diabetics with nonproliferative retinopathy is significantly larger than in healthy eyes due to the destruction of the parafoveal capillary net, although the area of the FAZ in healthy eyes could considerably vary. The importance of fluorescein angiography in measuring dimensions and shapes of the FAZ before treatment of diabetic maculopathy is pointed out. PMID- 1897171 TI - [Preoperative embolization of malignancies of the maxillofacial region]. AB - In 28 patients with malignoma of the maxillofacial region catheterization angiography by transfemoral route was applied. In the same act was performed preoperative embolization of the feeding arteries of the expansive formations by temporary embolization material--gel-foam particles. In all the treated patients good vascularization of expansive alterations was achieved as well as their demarcation from the healthy tissues which enables radical extirpation with reduced blood loss during intervention. PMID- 1897173 TI - [Changes in N-acetyl-beta-D-glucosaminidase in the urine of patients with pyelonephritis and glomerulonephritis]. AB - The activity of N-acetyl-beta-D-glucosaminidase (NAGase) activity was determined in urine of patients with pyelonephritis and glomerulonephritis. Determination was done with the non-commercial "Boehringer-Mannheim" test reagents for research purposes only. The protein concentrations were measured in the same samples. The obtained results were compared with results obtained in the control group and the significant increase (p less than 0.001) in NAGase activity was found in both groups of patients. At the same time normal protein values were found in 33% of all cases. It can be concluded that NAGase is a more sensitive parameter for early detection of renal disease. PMID- 1897174 TI - [The effect of air pollution on the olfactory function]. AB - Studying effects of permanent air pollution on the olfactory function the author has found that the threshold of smell perception is increased due to damages of the olfactory mucosa of the receptor organs. Changes in the olfactory function start in the early youth so that the examinees are not aware of their deficient olfactory function. The author advocates undertaking of more active measures for general protection of the human environment. PMID- 1897175 TI - [Factors relevant to the evaluation of the degree of severity of tibial fractures and their classification]. PMID- 1897176 TI - [The role of peroxide oxidation of lipids in the etiopathogenesis of atherosclerosis]. PMID- 1897177 TI - [Vestibular illusions and spatial disorientation during flight]. PMID- 1897178 TI - [Meige's syndrome (blepharospasm-oromandibular dystonia)]. PMID- 1897179 TI - [An unusual form of nodular lymphoid hyperplasia of the small intestine]. PMID- 1897181 TI - [Heterogeneity of serum albumin]. PMID- 1897180 TI - [Antineoplastic agents as inducers of tumor cell differentiation]. PMID- 1897182 TI - [Characteristics of various physico-chemical properties of vibrion neuraminidase]. AB - Some physico-chemical properties of commercially available neuraminidase preparations from non-choleric vibrio were studied. The neuraminidase was shown to be weakly acid glycoprotein with molecular mass 90 +/- 5 kDa, sedimentation constant 5.37 S and pI 5.0 +/- 0.1. As shown by roentgen-diffractometric technique the neuraminidase preparations possessed a quasi-crystalline structure. All the preparations studied were highly purified, exhibited electrophoretic homogeneity, did not contain any protein and Me+ contaminations. PMID- 1897184 TI - [Ganglioside (GD3) in serum of cancer patients]. AB - Gangliosides were studied in blood serum of healthy volunteers and of patients with cancer of mammary gland and stomach. Blood serum of the majority of patients with cancer and only 15% of healthy persons were shown to contain ganglioside GD3 which was detected in blood of patients with some other tumors. PMID- 1897183 TI - [Molecular mechanisms of cytotoxicity of narcotic drugs]. PMID- 1897185 TI - [The effect of a one-time fat load on indicators of the plasma lipoprotein system in patients with ischemic heart disease and in healthy patients]. AB - Effects of fatty loading on patterns of the lipoprotein system were studied in blood plasma of 39 patients with ischemic heart disease and of 21 healthy volunteers and were carried out on fasting individuals within 3 and 6 hrs after the loading. Alterations were detected in the lipoprotein system of the patients as compared with healthy persons. In the patients with ischemic heart disease content of apoI was not increased while subfraction of high density lipoproteins HDL3b was elevated within 3 hrs and cholesterol content was decreased within 6 hrs after the fatty loading. These alterations appear to be applicable as tests for detection of latent atherogenous defects in the HDL system. PMID- 1897186 TI - [Lipid peroxidation and change in the lipid fraction of plasma in patients with hypertonic disease]. AB - Effect of lipid peroxidation on content and composition of blood plasma lipids was studied in 20 patients with hypertension within various periods after hypertonic crisis. Alterations in blood plasma lipid spectrum were shown to be related to initiation of lipid peroxidation in cell membranes. Dynamics of lipid peroxidation in individual blood plasma lipid fractions appears to reflect the adaptation under conditions of the pathological state of the organism. PMID- 1897187 TI - [The pathogenetic significance of antioxidant properties of middle molecular weight peptides in thermal burns]. AB - Antioxidative activity of middle mass peptides (MMP), obtained from blood of dogs with burns and of intact animals, was studied. "Lowry-chromogenic" amino acids containing in the MMP structure were responsible for the antioxidative activity. At the same time, this property of MMP was related also to their pathogenecity. The peptides were able to regulate lipid peroxidation in rats with thermic burns. Regulating effects of MMP on lipid peroxidation in pathogenesis of burns are discussed. PMID- 1897188 TI - [Effect of hemosorption on the functional activity of leukocytes in psoriasis patients]. PMID- 1897189 TI - [Effect of the calcium antagonist diltiazem on the prostacyclin-thromboxane ratio in the plasma of ischemic heart disease patients]. AB - Content of prostacyclin and thromboxane was studied in blood plasma of patients with ischemic heart disease after single administration of calcium antagonist diltiazem. The drug caused an increase in content of prostacyclin and in the ratio prostacyclin/thromboxane. Diltiazem appears to differently affect the arachidonic acid metabolism in platelets and endothelial cells that may be involved in therapeutic effect of the drug under conditions of ischemic heart disease. PMID- 1897190 TI - [Permeability of erythrocyte membranes to monovalent ions in patients with stable stenocardia]. AB - Permeability of erythrocyte membrane for Na+ and K+, insensitive to glycosides, was impaired in patients with stable stenocardia of the II-III degree, especially distinct in 60-70 years old persons. Possible relationship is discussed between impaired transport of monovalent ions and increase in cholesterol content in membranes as well as deterioration of energy-rich substances consumption and alterations in blood rheological properties. PMID- 1897191 TI - [Level of R-proteins in blood during development of diabetes mellitus]. AB - R-proteins were studied in children with diabetes mellitus and in the risk group. The highest titre of the pattern was found in the children group where diabetes was the first to be detected. Normalization of the R-proteins high titre after insulin therapy was more typical for patients with first detected diabetes as compared with children impaired by the disease within 1-2 years. Content of immunoreactive insulin and titre of R-proteins correlated in the risk group. Estimation of the R-proteins titre simultaneously with other markers may be used for early diagnosis of diabetes mellitus as well as in control of the disease compensation. PMID- 1897192 TI - [Dynamics of glutathione metabolizing enzyme activity in experimental acute cholecystitis]. AB - Dynamics of glutathione-related enzymes activity was studied in erythrocytes of 22 dogs with destructive form of cholecystitis. As clinical symptoms of intoxication developed the enzymatic activity was decreased. In the animals with purulent-inflammatory complications distinct decrease was detected in activity of glutathione reductase (by 54.3%), glutathione-S-transferase--by 46.94% and glutathione peroxidase--by 42.1% (P less than 0.05). These data suggest that specific methods should be chosen for correction of impairments in the enzymatic activity in order to improve the treatment course efficiency as well as for prophylaxis of complications. The procedure developed for cholecystitis treatment, which involved channelled transport of antibiotics by means of autologous erythrocyte ghosts, proved to be more effective as compared with routine methods as shown by evaluation of the animals clinical state as well as by dynamics of hepato-specific enzymes activity and the glutathione-related enzymes activity. This procedure may be used in clinical practice; the laboratory tests described may serve for evaluation of the treatment course efficiency. PMID- 1897193 TI - [Study of the effect of an inhibitor of carnitine-dependent metabolism of mildronate on the oxidation of fatty acids in the liver mitochondria of intact rats]. AB - Effect af antiischemic drug mildronate 3-(2,2,2-trimethylhydrazinium) propionate on oxidation of sodium octanoate and L-palmitoyl carnitine was studied in liver mitochondria of intact rats using polarographic procedure. After 10 days of administration of mildronate at a dose of 200 mg/kg per os oxidation of sodium octanoate was stimulated in liver mitochondria while the rate of L-palmitoyl carnitine oxidation was unaltered. The data obtained suggest that mildronate stimulated the carnitine-independent fatty acid oxidation which appears to occur as a compensation for inhibition of the carnitine-dependent oxidation by the drug. PMID- 1897195 TI - [Selective inhibition of monoamine oxidase in bovine brain by befol and moclobemide]. AB - Effects of befol and moklobemide on thyramine-, serotonin- and 2-phenyl ethylamine deaminase activities of mitochondrial monoamine oxidase from bovine truncus cerebri were studied. These drugs are reversible noncompetitive inhibitors of the enzyme not requiring preincubation. They inhibited most effectively the serotonin deaminase activity as compared with phenyl ethylamine deaminase activity, however they should not be concerned with typical inhibitors of monoamine oxidases of the A type as inhibition of thyramine deaminase activity was not found. PMID- 1897194 TI - [Change in the catalytic properties of mitochondrial monoamine oxidase in experimental audiogenic epilepsy]. AB - Catalytic properties of mitochondrial monoamine oxidases (MAO) were studied in brain, heart, liver and kidney of rats of Krushinskii-Molodkina strain with inherited audiogenic epilepsia. In brain of these rats a. 2.5-fold decrease of Vmax of serotonin (MAO-A substrate) deamination has been found. During audiogenic epileptiformic attack 2.5-5-fold decrease of Vmax of serotonin deamination in brain and liver and also decrease of benzylamine (MAO-B substrate) oxidation in brain were found. Simultaneously oxidation of glucosamine and gamma-aminobutyric acid was markedly increased (up to 5-fold and more) in brain. The data obtained showed that qualitative transformation occurred in catalytic properties of MAO which may be an important pathogenic factor in the development of epileptiformic attack. PMID- 1897196 TI - [The connection between the decomposition of mature collagen and the level of natural cytotoxicity in patients with focal scleroderma]. AB - Increased rate of pyridinoline excretion with urine was detected in patients with focal sclerodermia: the ratio pyridinoline/creatinine was equal to 0.094 +/- 0.049 as compared with that of 0.073 +/- 0.049 in controls. Concentration of mature collagen cross-links involving pyridinoline structure in urine of patients with focal sclerodermia did not depend on the patients age and the disease duration. However, this pattern correlated distinctly with clinical form of the disease (0.073 +/- 0.049 in local form and 0.013 +/- 0.017 in generalized form of sclerodermia) as well as correlated reversely with the rate of activity of natural killer cells (r = -0.977). PMID- 1897197 TI - [Detection and identification of new cardioactive proteins in cattle heart]. AB - Seven cardioactive polypeptides were identified in precardiac and auricular regions of bovine heart. Procedures used for purification of the polypeptides involved extraction of water-soluble proteins, fractionation by ammonium sulfate, gel filtration on Sephadex G-100, chromatography and rechromatography on DEAE cellulose. Some physico-chemical and biological properties were studied; amino acid composition, N-terminal amino acids, molecular mass and the effects on coronary blood vessels. The data obtained suggest that multiple forms of these proteins may exist either as a result of partial hydrolysis of large molecules or due to processing of precursors. PMID- 1897198 TI - [Potentiation of the antiketogenic effect of exogenous glucose with the help of the new beta-oxidation inhibitor mildronate--3-(2,2,2 trimethylhydrazine)propionate]. AB - Antiketogenic effect of exogenous glucose (2 g/kg, per os, 1 hr before death) was potentiated after preadministration of mildronate 3-(2,2,2-trimethylhydrazinium) propionate into rats either kept on usual ration or fasting within 48 hrs at a dose of 200 and 400 mg/kg, per os, during 10 days. Mildronate is inhibitor of carnitine-dependent metabolism of fatty acids affecting at the step of gamma butyrobetaine turnover into carnitine. The drug inhibitory influence studied appears to be realized via activation of the glycolytic pathway of glucose metabolism specific for inhibitors of beta-oxidation. PMID- 1897199 TI - [The role of cyclic nucleotides in adaptation of the gastric mucosa to hypoxia]. AB - State of oxygen consumption in gastric mucosal membrane evaluated by means of pO2 measurement as well as metabolism of cyclic nucleotides were studied in patients with ulcerous disease. Hypoxia of periulcerous area and alterations in functional activity of the cyclase systems were detected. Reciprocal alterations in the cyclases activity, as a result of which the ratio of cyclic nucleotides was changed under dissimilar conditions of oxygen consumption in gastric mucosal membrane, were considered as essential adaptive reaction related to maintenance of proliferation under conditions of oxygen and energy rich substances deficiency. PMID- 1897200 TI - [Relationship of the changes in catecholamines, thiol compounds, and lipid peroxidation in bronchial asthma]. AB - Dynamics of adrenaline (A), noradrenaline, SH-groups and lipid peroxidation (LP) was studied in 34 patients with chronic asthmatic bronchitis and in 132 patients with bronchial asthma. The data obtained suggest that ratios A.10/LP and SOD/SH.10 enabled to evaluate the disease compensation or transformation of asthmatic attack into asthmatic state as well as to differentiate chronic asthmatic bronchitis from bronchial asthma. PMID- 1897201 TI - [Determination of nitrate reductase activity in mixed saliva]. AB - A procedure is developed for estimation of nitrate reductase activity in saliva. Effects of pH, temperature and nature of electron donor on the enzymatic activity were studied. The maximal enzymatic activity was found at pH 6.5-7.0; heating and freezing of saliva led to loss of the enzymatic activity. Salivary nitrate reductases are of microbial origin and belong to "terminal" type of nitrate reductases. The enzyme activity varied in the interval 0.8-17.3 mmole/min per I L saliva and did not depend on human sex. PMID- 1897203 TI - [Flow injection analysis in clinical biochemistry]. PMID- 1897202 TI - [[Elimination of toxins from the body using electrochemical oxidation]. AB - Potentialities of electrochemical procedures were considered in simulation of liver monooxygenases functions directed to clearance of blood and tissues from toxic and ballast substances by means of hydroxylating oxidation. Electrooxidation of specific endogenous toxin bilirubin, catalyzed by platinum electrode, was studied in model physiological solutions, blood, lymph and blood plasma. Three problems developed during direct electrooxidation of toxins in blood: efficiency of electrochemical cell, "protein protection" of the toxin, compatibility of electrochemical cell and blood. Influences of electrochemical oxidation on various patterns of intact animal homeostasis were studied as well as efficiency of the oxidation in a body was shown. Artificial detoxicating system was elaborated for clinical purpose using these experimental data. PMID- 1897204 TI - [Electrophoretic analysis of rat kidney glomerulus basal membrane]. AB - A technique was developed for analysis of basal membrane proteins from rat kidney glomerulus using two-dimensional electrophoresis by O'Farrell. Basal membranes were isolated from the glomerulus by means of detergent treatment. Various procedures of basal membrane solubilization were studied. About 25 protein fractions with molecular mass from 25 kDa to 330 kDa were detected in the basal membrane after single-dimensional electrophoresis in presence of sodium dodecyl sulfate. Two-dimensional electrophoresis of the basal membrane proteins and staining of gels with silver nitrate enabled to detect approximately 50 polypeptide fractions with molecular mass from 25 kDa up to 250 kDa at pH 5-7. PMID- 1897206 TI - [Methodical biochemical assurance of multichannel biochemical analyzers made by the company "Abbott Laboratories"]. PMID- 1897205 TI - [Evaluation of the operation of the automated microbiological system MS-2 from the company "Abbott Laboratories" (USA) in a clinical microbiological laboratory]. PMID- 1897207 TI - Demands of illness among chronically ill women. PMID- 1897208 TI - Women's decisions about estrogen replacement therapy. PMID- 1897209 TI - Parental perceptions of caring following perinatal bereavement. PMID- 1897210 TI - Obstetrical role strain for male nursing students. PMID- 1897212 TI - A member check procedure to enhance rigor in naturalistic research. PMID- 1897211 TI - Sources of work satisfaction/dissatisfaction for hospital registered nurses. PMID- 1897213 TI - Reviewing the decision-making process used in the analysis of data. PMID- 1897214 TI - Computerized nursing information in eastern Europe. PMID- 1897215 TI - Proposed role of a clinical conceptual framework in the development of a research program. PMID- 1897216 TI - Student/faculty roles in writing research papers. PMID- 1897217 TI - Standardized care issues across cultures. PMID- 1897218 TI - Family instrument selection and study fit. PMID- 1897219 TI - Sick sinus syndrome and primary systemic amyloidosis. AB - A sixty-eight-year-old woman with documented sick sinus syndrome was found to have, five year later, florid clinical features of systemic amyloidosis which only then led to recognition of an underlying IgA, Kappa paraproteinaemia. The literature on this association is outlined. Underlying plasma cell dyscrasias should be excluded in cases of unexplained sick sinus syndrome. PMID- 1897220 TI - A health situation analysis in Trinidad and Tobago, 1990. The local health systems approach. AB - This HSA exercise confirmed known patterns of health and disease in Trinidad and Tobago but produced valuable new information on health status, particularly as it relates to the different local health administrative areas. This was perhaps the most valuable aspect of the analysis. We cannot overemphasize the need for disaggregated data as summary statistics often mask the true state of affairs. This report has focussed on the health status of the population and emphasized again the dominant role of chronic non-communicable diseases and accidents as causes of death. Among males, aged 15-44 years, AIDS was the third leading cause of death in 1987, and can be expected to become even more important as a cause of death over the next few years. Other and equally important information on the status of the health information system and the health services situation was also produced and will be discussed elsewhere. PMID- 1897221 TI - The judicious use of the gift of life. PMID- 1897222 TI - Jamaican patients' understanding of diabetes mellitus. AB - Ambulant and hospitalized patients with diabetes mellitus were interviewed by two trained interviewers to obtain information about their knowledge of the illness and the communication they had received about it. Sixty to seventy per cent of patients claimed that no explanation about the illness was given to them at the time of diagnosis. This poor communication occurred in both public and private medical services. Fifty-seven per cent of the patients scored no more than the 50th percentile on the knowledge rating score, reflecting that patients' knowledge of the illness was in general poor. The hospitalized patients did learn about the illness while there, but still claimed that they learnt nothing. These data are examined in the context of the nature of the doctor-patient communication style and effect. Jamaican diabetic patients need to be better informed about their illness; despite short patient-physician contact time, an effort to explain the nature of the illness at the time of diagnosis would be worthwhile. This will need subsequent assessment and reinforcement by involving a team approach. PMID- 1897223 TI - Questionnaire detection of problem drinkers among acute medical admissions. AB - The study was designed to determine the prevalence of alcoholism/problem drinking among emergency medical admissions. Of 203 emergency admissions to two medical wards, 18% were found to be problem drinkers, using the brief Michigan alcoholic screening test (MAST) questionnaire. Problem drinking was found in 31% of males and 5% of females. Most drinking was done with friends (77%) and at the "rum shop" (62%). Fifty-one per cent of problem drinkers started between the ages of sixteen and twenty years. Seventy per cent of all problem drinkers had a first degree family relative who drank compared to 28% of non-drinkers. A high prevalence of alcoholism (48%) was found among smokers. Housestaff detected just over half of male (56%) and female (60%) alcoholics who were MAST-positive. Medical diagnoses among MAST-positive patients were gastrointestinal (cirrhosis, pancreatitis and hepatitis) in 32%, neurological (delirium tremens, seizures and subdural hematoma) in 27% and cardiovascular (cardiomyopathy, heart failure and dysrhythmias) in 16%. The detected level of problem drinking is likely to cause significant morbidity, and allows an important opportunity for intervention. The use of questionnaire methods to screen for alcoholism needs further evaluation in the region. PMID- 1897224 TI - Suicide by poisoning. AB - An epidemiological evaluation was conducted on 270 patients who died at the General Hospital, Port-of-Spain after presenting with deliberate self-poisoning between January, 1986 and June, 1990. The cause of death was confirmed by autopsy and toxicological analysis. Epidemiological variables of age, sex, race, precipitating factors and types of poison used were assessed. It was found that the male to female ratio was 2.7:1. East Indians accounted for 54.4%, Africans 42.0%, people of mixed ethnic origin 3% and Caucasians 0.6%. The majority of cases (52.6%) were seen in the age group 11-34 years. "Lovers' quarrels" (35.4% of cases), psychiatric illness (27.8% of cases) and family disputes (27% of cases) were reported as the most frequent precipitating events in suicide. East Indians predominated in those suicides precipitated by "lovers' quarrels" and family disputes, accounting for 63.2% and 58.9% of these cases, respectively; while for those suicides in which psychiatric illnesses were the main precipitating event. Africans were represented by 53.3% and East Indians 45.3%. Depression was the most common psychiatric illness diagnosed. Paraquat was the most popular poison used in 63.7% of the suicidal cases, and other agrochemicals were used in 20% of cases. PMID- 1897225 TI - Cancer incidence and mortality in Antigua/Barbuda. AB - An inquiry into the incidence and mortality of malignant neoplasms in Antigua/Barbuda was undertaken to document the magnitude of the disease. The top ranking cancers diagnosed in 114 males were skin (26.3%), prostate (22.8%) and upper respiratory and alimentary tract (10.5%). In 130 females, the 3 main cancers were breast (23.1%), cervix uteri (22.3%), and skin (15.3%). The main cancers causing death were stomach (22.3%) and prostate (17.8%) in 157 males; and breast (18.2%) and cervix uteri (14.1%) in 149 females. Imprecise documentation, insufficient clinico-pathological correlation and the finding of advanced cancers underscore the need for a cancer registry and cancer society in Antigua/Barbuda. PMID- 1897226 TI - Management of colonic polyps by colonoscopic polypectomy. AB - Colonoscopic polypectomy is an important therapeutic advance as it enables most colonic polyps to be removed entirely and studied pathologically and has virtually replaced surgical treatment. The clinical and pathological features of patients with colonic polyps treated by colonoscopic polypectomy over a five-year period are reported. Seventy-four patients (37 men, 37 women) with a mean age of 57 years had 109 polyps removed by snare polypectomy. Rectal bleeding was the predominant symptom and was present in 63.5%. Lower abdominal pain was present in 12%. The majority of polyps were located in the sigmoid (38.5%) and descending (40.3%) colon. Ninety-five polyps were pedunculated and 14 were sessile. Of the neoplastic polyps, 61.6% were pure tubular adenomas, 25.2% were mixed tubulo villous adenomas and 1% were pure villous adenomas. There were no complications arising from colonoscopy or snare polypectomy. Colonoscopic polypectomy is a safe, reliable and cost-effective therapeutic procedure that has revolutionized the management of pre-cancerous neoplastic colonic polyps. PMID- 1897227 TI - Another look at the effects of advanced maternal age. AB - The reproductive performance of primigravidae aged 30 years and over was compared with that of a group of younger primigravidae. Other patients were at greater risk for antepartum complications such as pre-eclampsia and uterine fibroids. Induction of labour was undertaken more frequently, and the Caesarean Section rate was higher but there was no worsening of perinatal mortality. PMID- 1897228 TI - Perinatal implications for macrosomic babies. AB - A five-year record review was undertaken for all babies with a diagnosis of foetal macrosomia. The perinatal mortality rate of 23 per 1,000 total births was similar to the overall hospital rate. Neonatal morbidity was significant, and the most important contributory factor to foetal injury was impaction of the shoulders during parturition. In order to avoid this catastrophe, elective abdominal delivery may be prudent if the foetal weight is estimated at greater than 4,500 grams. PMID- 1897229 TI - Spontaneous rupture of the normal colon. AB - A case of spontaneous rupture of the colon in a previously asymptomatic patient is herein reported. At laparotomy, apart from the tear in the sigmoid colon, no other pathological problem was present. An awareness of the existence of this condition will lead to early diagnosis and management with improved morbidity and mortality. PMID- 1897231 TI - Report on the XV Congress of the European Society for Medical Oncology (ESMO) Copenhagen, December 2-5, 1990. PMID- 1897230 TI - [Effect of bezafibrate in isolated hypercholesterolemia and mixed hyperlipidemia on infarct risk (Stepwise Program for Individual Risk Identification and Therapy): an open multicenter study]. AB - The therapeutic effect of bezafibrate (1 x 400 mg/day) on plasma lipids and coronary risk was evaluated in an open, prospective multicenter study in 763 patients with isolated hypercholesterolemia or mixed hyperlipidemia. During the 16 weeks of treatment (712 patients were included in the evaluation) bezafibrate lowered total cholesterol (C) by 22%, triglycerides (TG) by 32% and LDL-C by 20% and increased HDL-C by 29.6%. The ratio of C/HDL-C decreased from 8.8 +/- 2.0 to 5.4 +/- 1.5, i.e. a reduction of 36%. A comparable hypolipemic effect of bezafibrate was seen in all the subgroups of isolated hypercholesterolemia (C 21%, LDL-C -31%, HDL-C + 28%, TG -10%) and mixed hyperlipidemia (C -22%, LDL-C 16%, HDL-C + 30%, TG -37%). During treatment the coronary risk factor estimated by the SPIRIT calculator decreased from 5.5 to 2.5 (-54.5%) in male patients (n = 499). The calculated incidence of myocardial infarction thereby decreased from 225.7 to 111.9 (-50.4%). This study shows that bezafibrate effectively improves lipid metabolism in both isolated hypercholesterolemia and mixed hyperlipidemia and results in a decreased coronary risk. PMID- 1897232 TI - Long term remission of intrinsic brainstem gliomas: the case reports of two children. AB - Intrinsic brainstem gliomas carry the worst prognosis of all pediatric CNS tumors; only 10-25% of patients are expected to survive for more than two years. Over a period of four years seven intrinsic brainstem gliomas were diagnosed in children in one institution. Four of them underwent a rapidly fatal course, whilst one was diagnosed only two years ago, which is too recent for long-term evaluation. We report the case histories of the remaining two boys, who showed a favorable course of their disease. Presenting symptoms were headaches and signs of brainstem dysfunction with multiple bilateral cranial nerve palsies, ataxia and pyramidal tract signs. Diagnosis rested on neuroimaging (CAT scans and/or MRI scans). Both tumors were intrinsic brainstem gliomas, one diffuse and the other focal. They responded to treatment (radiotherapy and chemotherapy in the former patient and radiotherapy alone in the latter patient). The two boys became long term survivors and have remained well, without evidence of disease, for more than 71 and 61 months, respectively, after completion of treatment. They are probably cured. Prompt therapy with curative intention is recommended, with consistent adherence to the chosen antitumor regimen even in poor-risk brainstem gliomas. PMID- 1897234 TI - Financing catastrophic health care costs. PMID- 1897233 TI - [Cutaneous, cellular immunity in malignant melanoma]. PMID- 1897235 TI - C-section editorial draws fire. PMID- 1897236 TI - Malaria in Wisconsin 1981-1989: a review of cases and update on chemoprophylaxis. AB - Malaria continues to be a significant cause of travel related morbidity and mortality for US citizens. Yet there have been no previous analyses of malaria cases reported in Wisconsin. To provide timely information to Wisconsin physicians, the authors present a review of reported malaria cases in Wisconsin for the years 1981 through 1989, and an update of current Center for Disease Control malaria chemoprophylaxis. PMID- 1897237 TI - Human ehrlichiosis diagnosed in Wisconsin. AB - A man developed a febrile illness shortly after he returned to Wisconsin from Florida, where he had received tick bites. This illness was associated with a rash, thrombocytopenia, leukopenia, and elevated hepatic enzymes, and it resolved on doxycycline. Serologic studies confirmed ehrlichiosis, a tick-borne rickettsial intraleukocytic infection endemic to the Southeastern United States. This case expands the spectrum of tick-borne illnesses that must be considered by Wisconsin clinicians. PMID- 1897238 TI - Electromagnetic induced shock wave therapy of ureteral calculi. AB - Between March 1989 and July 1990, 86 patients with ureteral stones were treated with electromagnetic induced extracorporeal shock wave lithotripsy at our facility, of which 77 were available for follow-up. Sixty-one of the patients were male, 16 were female, and the average age was 53.8 +/- 16.0 (11-84). Seventy four of the patients were treated with intravenous sedation. One patient required general anesthesia and two other patients requested no sedation. Sixty-four of 77 (83%) patients were stone free after therapy, 59 of 77 (77%) after a single treatment, and 5 of 9 (56%) after a second treatment. Thirteen patients were hospitalized post therapy, however, 6 had been hospitalized pretreatment because of pain or obstruction. Four major complications were encountered: hematoma (1), ureteral stricture (1), urinary extravasation (1), and proximal stent migration (1). There were no statistically significant differences between stone free and non-stone free patients when comparing for sex, age, stone size, number of shocks, maximum kilovoltage, or duration of symptoms pretreatment. The patients who had unsuccessful treatment, however, were noted to have a significantly greater incidence of distal stones (69% v 39%) (P less than .05). PMID- 1897239 TI - Kawasaki syndrome in Wisconsin. AB - We reviewed cases of Kawasaki syndrome reported to the Wisconsin Division of Health and occurring in Wisconsin residents with illness onsets between 1982 and 1989. Of 164 reports, there were 73 confirmed cases that met the Centers for Disease Control case definition criteria for Kawasaki syndrome, 87 probable cases, and four non-cases. Confirmed cases were reported in residents of all five Wisconsin public health regions. The Wisconsin data was demographically similar to national data: 80% of the cases occurred in children younger than 5 years old, the mean annual incidence rate was highest in children 12 to 23 months of age, males were affected more often than females, and the incidence rate was higher among non-white children than among white children. Coronary artery aneurysms occurred in 16% of the patients with confirmed cases. Males developed aneurysms significantly more often than females, and aneurysm formation did not correlate with age. Kawasaki syndrome continues to occur in Wisconsin, and complete and accurate reporting of the disease will enhance the understanding of its natural history and etiology. PMID- 1897240 TI - Data-based cancer control programs: a public health response. PMID- 1897241 TI - SMS helps develop cost containment proposals. PMID- 1897242 TI - SMS membership survey executive summary. PMID- 1897243 TI - Distribution and elimination in vivo of polychlorinated biphenyl (PCB) isomers and congeners in the pigeon. AB - 1. Pigeons were injected with a single dose of commercial PCB mixtures (Aroclor 1248 plus Aroclor 1260), killed 120 h later and the abundance of individual PCBs was determined in adipose tissue, gonads, liver, brain, kidney, heart, muscle and blood. 2. Elimination factors for individual PCBs were calculated. Values of greater than 1 were obtained for PCBs with meta-para-unsubstituted carbon atoms in at least one ring, indicating that elimination exceeded accumulation in all or most tissues. By contrast, ortho-meta unsubstituted PCBs had elimination factors less than 1, thus indicating their impaired removal. 3. Tissues with high microsomal monooxygenase activity had the highest elimination factors for individual PCBs (i.e. liver greater than kidney greater than muscle greater than heart). 4. Distribution of individual PCBs was independent of sex and of ortho chlorine substitution and showed that 90% of total PCBs in cadavers was present in adipose tissue, 2% in kidneys, 1% each in brain, muscle and heart and less than 0.1% in blood. 5. The distribution of the highly toxic non-ortho and mono ortho substituted PCBs did not differ amongst all tissues analysed. 6. The present studies indicate that elimination of PCBs in vivo is favoured by the molecular feature of unsubstituted meta-para carbon atoms in the biphenyl moiety. PMID- 1897244 TI - Characterization of the principal metabolite of quinine in human urine by 1H n.m.r. spectroscopy. AB - 1. The major metabolite of quinine in human urine, which is also the sole metabolite in human plasma and saliva, has been identified and characterized by chemical ionization mass spectrometry and 1H-n.m.r. spectrometry. 2. The mass spectrum showed that an oxygen atom is incorporated in the quinuclidine nucleus, and the exact position of the oxidation was established from the n.m.r. spectrum to be at the C-3 position. PMID- 1897246 TI - Characterization and induction of xenobiotic metabolizing enzyme activities in a primary culture of rainbow trout hepatocytes. AB - 1. A primary cell culture from rainbow trout (Oncorhynchus mykiss) liver was prepared and evaluated for biotransformation of xenobiotics. 2. The hepatocytes maintained cytochrome P-450 content, as well as their cytochrome P-450-dependent activities, stable for 5-6 days in serum-free medium. Protein and glutathione levels, as well as other enzyme activities important for biotransformation, were close to their fresh cell levels throughout the culture period. 3. The cells were also responsive to cytochrome P-450 inducers. Both beta-naphthoflavone (BNF) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) caused an increase in ethoxyresorufin O-deethylase (EROD) activity, which was dose-dependent over the concentration ranges of 3.6-360 nM and 2.5-100 pM, respectively. The induced activities in BNF exposed cells returned to basal levels within 48 h after replacing the medium with a BNF-free medium. Exposure of cells to TCDD (100 pM) for 48 h induced EROD activity which, in contrast to response of BNF-exposed cells, continued to increase after the medium had been replaced with TCDD-free medium. 4. The results show that trout hepatocytes in primary culture afford a reliable in vitro method for studying the regulation and functions of xenobiotic biotransformation enzymes, and for defining toxic effects of aquatic pollutants in cells. PMID- 1897245 TI - Thiopurine methyltransferase regulation in rat kidney: immunoprecipitation studies. AB - 1. Thiopurine methyltransferase (TPMT) catalyses the S-methylation of thiopurine drugs. TPMT activity in the kidneys of male Sprague-Dawley (S-D) rats is approximately twice that present in the kidneys of female S-D rats, and this difference is testosterone-dependent. Renal TPMT activities in these animals also increase dramatically during growth and development. 2. Our studies were conducted to determine whether variations in TMPT activity in the S-D rat kidney were due to differences in the quantity of TPMT protein. Rabbit polyclonal antibodies to partially purified rat kidney TPMT were used to develop an immunoprecipitation assay for immunoreactive TPMT protein. 3. Gender-related differences in renal TPMT activities in S-D rats were due to a lower content of immunoreactive TPMT protein in kidneys of female animals. TPMT enzyme activities and immunoreactive protein levels were also directly correlated in renal preparations from castrated and sham-operated male rats, from testosterone treated castrated and sham-operated male rats, and from testosterone-treated and control female rats. 4. There was also a significant positive correlation between TPMT enzymic activities and immunoreactive TPMT protein levels in renal tissue from different aged male S-D rats (rs = 0.955, n = 15, P less than 0.001.) 5. These results demonstrate that changes in S-D kidney TPMT activity during growth and development, in the two sexes and in response to testosterone, were due to variations in the quantity of immunoreactive TPMT protein. PMID- 1897247 TI - Stereoselectivity of idarubicin reduction in various animal species and humans. AB - 1. The (13S)-dihydro derivative of idarubicin, (13S)-idarubicinol, is the major urinary metabolite of idarubicin in humans. Idarubicinol epimers were quantified by h.p.l.c. in urine from rats, mice, rabbits, dogs and man after i.v. administration of idarubicin, and in man after oral dosing. The (13R)- and (13S) epimers of idarubicinol were determined in rat bile. 2. After i.v. injection of idarubicin. (13R)-idarubicinol was not detectable in mice and rabbit urine and no more than 0.5% of the dose was present in the urine of other species. In man, the proportion of (13R)-idarubicinol in total idarubicinol was similar after i.v. (4.1%) and oral (3.8-5.0%) administration of idarubicin; the same applies to rat bile and urine. 3. Reduction of idarubicin in vivo is dependent upon ketone reductases, and proceeds more stereoselectively than that of most ketones giving rise to the (13S)-epimer almost exclusively. The high stereospecificity in idarubicin reduction might result from chiral induction due to the presence of asymmetric centres near to the carbonyl group in idarubicin. PMID- 1897248 TI - Neonatal exposure to Aroclor 1254: effects on adult hepatic testosterone hydroxylase activities. AB - 1. The effects of neonatal exposure to Aroclor 1254 (100 mumol/kg) on the metabolism of testosterone by adult male and female rats were determined by comparing their hepatic microsomal testosterone hydroxylase activities at 60, 90 and 120 days after the initial exposure. 2. The most pronounced effects in male rats were observed 90 days after treatment with Aroclor 1254, whereas in female rats the major changes in testosterone hydroxylase activities were observed after 60 days. 3. Ninety-day-old male rats neonatally treated with Aroclor 1254 exhibited decreased basal testosterone 7 alpha-hydroxylase and increased basal testosterone 16 alpha-, 2 alpha- and 15 beta-hydroxylase activities and androstenedione formation. In addition, the Aroclor 1254-mediated induction of testosterone 7 alpha- and 6 alpha-hydroxylase activities and androstenedione formation was decreased, and that of testosterone 2 beta- and 15 beta-hydroxylase activities was increased. 4. Sixty-day-old female rats exposed neonatally to Aroclor 1254 exhibited increased basal testosterone 16 alpha-, 2 beta-, 6 alpha- and 15 beta-hydroxylase activities and androstenedione formation, and increased Aroclor 1254-induced metabolism of testosterone at all positions except 16 alpha and 2 alpha. 5. Changes in testosterone hydroxylase activities indicative of permanent damage (or imprinting) in androgen metabolism, i.e. altered activities in 120-day-old animals, were observed only in male rats. These activities included basal testosterone 6 beta-, 16 alpha- and 2 alpha-hydroxylase activities and androstenedione formation. PMID- 1897249 TI - The uptake of oestrone from the lumen of the isolated perfused rat gut. AB - 1. In the isolated perfused rat gut oestrone was not taken up from the perfusate but was rapidly taken up from the gut lumen when administered in dimethyl sulphoxide or in 10% acetone in water. 2. Uptake from corn oil was much slower and the rate was concentration-dependent. 3. When given in dimethyl sulphoxide or in aqueous acetone, the residual oestrone in the gut lumen was largely unchanged, with only about 10% being present as the glucuronide. Of the oestrone in the gut perfusate, some 40% was glucuronidated. 4. No evidence was obtained for any reduction or hydroxylation, or for any sulphation, during uptake of oestrone by the gut. 5. No secretion of oestrone or its metabolites into lymph could be detected. PMID- 1897250 TI - Effect of inducers of cytochrome P-450 on the metabolism of [3-14C]coumarin by rat hepatic microsomes. AB - 1. The metabolism of [3-14C]coumarin has been studied in rat hepatic microsomes and with two purified cytochrome P-450 isoenzymes. 2. [3-14C]Coumarin was converted by liver microsomes to several polar products including 3- and/or 5 hydroxycoumarin, omicron-hydroxyphenylacetic acid and a major unidentified novel coumarin metabolite. 3. [3-14C]Coumarin was also converted to reactive metabolite(s) as indicated by covalent binding to proteins, and by the depletion of reduced glutathione added to the microsomal incubations. 4. [3-14C]Coumarin metabolism to polar and covalently bound metabolites by rat liver microsomes was induced by pretreatment with phenobarbitone, 3-methylcholanthrene, beta naphthoflavone, Aroclor 1254 and isosafrole; but not by dexamethasone or nafenopin. 5. The profile of [3-14C]coumarin metabolism to polar products was similar in control and pretreated liver microsomes and in incubations with purified cytochrome P450 IA1 and P450 IIB1 isoenzymes. 6. The results indicate that coumarin is a substrate for isoenzymes of the cytochrome P450 IA and P450 IIB subfamilies. The bioactivation of coumarin by rat hepatic microsomes is postulated to result in the formation of a coumarin 3,4-epoxide intermediate which may rearrange to 3-hydroxycoumarin, be further metabolized to a coumarin 3,4-dihydrodiol, or form a glutathione conjugate. PMID- 1897251 TI - Metabolism and elimination of benzocaine by rainbow trout, Oncorhynchus mykiss. AB - 1. Branchial and urinary elimination of benzocaine residues was evaluated in adult rainbow trout, Oncorhynchus mykiss, given a single dorsal aortic dose of 14C-benzocaine hydrochloride. 2. Branchial elimination of benzocaine residues was rapid and accounted for 59.2% of the dose during the first 3 h after dosing. Renal elimination of radioactivity was considerably slower; the kidney excreted 2.7% dose within 3 h and 9.0% within 24 h. Gallbladder bile contained 2.0% dose 24 h after injection. 3. Of the radioactivity in radiochromatograms from water taken 3 min after injection, 87.3% was benzocaine and 12.7% was N-acetylated benzocaine. After 60 min, 32.7% was benzocaine and 67.3% was N-acetylated benzocaine. 4. Of the radioactivity in radiochromatograms from urine taken 1 h after dosing, 7.6% was para-aminobenzoic acid, 59.7% was N-acetylated para aminobenzoic acid, 19.5% was benzocaine, and 8.0% was N-acetylated benzocaine. The proportion of the radioactivity in urine changed with time so that by 20 h, 1.0% was para-aminobenzoic acid and 96.6% was N-acetylated para-aminobenzoic acid. 5. Benzocaine and a more hydrophobic metabolite, N-acetylated benzocaine, were eliminated primarily through the gills; renal and biliary pathways were less significant elimination routes for benzocaine residues. PMID- 1897252 TI - Premercapturic acid metabolites of bromobenzene derived via its 2,3- and 3,4 oxide metabolites. AB - 1. A new premercapturic acid metabolite of bromobenzene was isolated from the urine of beta-naphthoflavone-induced rats; using 1H-n.m.r., FAB mass spectrometry and chemical degradation it was identified as S-(2-hydroxy-3-bromocyclohexa-3,5 dienyl)-N-acetylcysteine. 2. Two regioisomeric premercapturic acids apparently derived from bromobenzene-3,4-oxide were isolated as an inseparable 1:1 mixture from the urine of phenobarbital-induced rats and characterized by similar means. 3. Acid dehydration of bromobenzene 3,4- and 4,3-premercapturic acids (mixture) afforded only p-bromophenylmercapturic acid, whereas acid dehydration of 3,2 premercapturic acid gave both o- and m-bromophenylmercapturic acids. This implies a shift of sulphur in acid dehydration of the 3,4- and 3,2- but not the 4,3 premercapturic acids. 4. Base dehydration of the 3,4- and 4,3-premercapturic acid mixture gave a mixture of p- and m-bromophenylmercapturic acids, whereas base dehydration of the 3,2-premercapturic acid gave only m-bromophenylmercapturic acid. This indicates these premercapturic acids dehydrate by direct elimination without rearrangment. 5. The 3,2-premercapturic acid was detected only in the urine of BNF-induced animals, whereas the 3,4- and 4,3-premercapturic acids were detected in the urines of untreated as well as PB- and BNF-induced animals. 6. Together with earlier reports of the isolation of the 2,3-dihydrodiol, the isolation of the 3,2-premercapturic acid as a urinary metabolite of bromobenzene implies that bromobenzene-2,3-oxide is a discrete metabolite of bromobenzene and not merely a hypothetical intermediate. PMID- 1897253 TI - Nonlinear first-pass metabolism of nifedipine in healthy subjects. AB - 1. A dose-range study was carried out with nifedipine (NF) in 11 healthy subjects, who received orally 5, 10 and 20 mg in capsules (cap) and 20 mg as slow release tablet. 2. The dose-normalized area under the curve (AUC) of NF showed significant nonlinearity: AUC of 5 mg (cap) was 312 +/- 179, of 10 mg (cap) 357 +/- 186 and of 20 mg (cap) 424 +/- 174 (ng.h/ml). The AUC of the tablet was significantly lower than that of 10 and 20 mg (cap), but not different from 5 mg (cap). 3. The dose-normalized AUC of the pyridine metabolite (M-0) significantly decreased with increasing dose: AUC of 5 mg (cap) was 244 +/- 88, of 10 mg (cap) 194 +/- 96 and of 20 mg (cap) 120 +/- 37 (ng.h/ml). 4. The excretion of M-I (which is ester-hydrolysed M-0) into urine was not different for any of the doses. 5. It is concluded that NF exhibits nonlinear first-pass metabolism, which concomitantly affects the formation of M-0, but not that of M-I. PMID- 1897254 TI - New technologies for genetic and newborn screening: a medical, legal, and ethical update. April 23, 1990. PMID- 1897255 TI - Newborn screening perspective. PMID- 1897256 TI - Implementation of DNA technology. PMID- 1897257 TI - New technologies in newborn screening. PMID- 1897259 TI - Introduction: new technologies for genetic and newborn screening. AB - Screening newborn infants for inherited disorders has been effective in preventing mental retardation, growth failure, and death from several metabolic disorders for more than two decades. Technical advances have provided more screening tools for both genetic and nongenetic conditions, and in the coming decades these techniques will be used not only to screen newborns but to assess genetic risks in entire populations. The financial, legal, and ethical issues which these activities raise must influence the development of public policies in order to reap the benefits promised. The conference published here was designed to address these issues for health care practitioners, health policy planners, and public health professionals. PMID- 1897258 TI - Legal aspects of genetic information. AB - The federally funded Human Genome Initiative will lead to the development of new capabilities to learn about an individual's genetic status. Legal issues are raised concerning patients' and other parties' access to that information. This article discusses the effect of existing statutes and case law on three pivotal questions: To what sort of information are people entitled? What control should people have over their genetic information? Do people have a right to refuse genetic information? The article emphasizes that the law protects a patient's right to obtain or refuse genetic information about oneself, as well as the right to control the dissemination of that information to others. PMID- 1897260 TI - Rights, privacy, and genetic screening. PMID- 1897261 TI - The context of genetic screening. PMID- 1897262 TI - Genetic screening and the insurance industry. PMID- 1897263 TI - Some factors that influence the plasma lipoprotein 1H NMR spectra of normal and cancer patients: an oncolipid test? AB - Selected factors have been evaluated in order to determine their influences on the plasma lipoprotein proton NMR spectra of normal and cancer patients. The variables were donor's diet (fasting/non-fasting), temperature and time of sample storage, processing procedure, centrifugation speed, and water pre-saturation time. Plasma samples from fasting individuals that were placed immediately on ice, spun at 1,000 and 3,000 g for 15 minutes, and the proton NMR spectrum acquired with the Carr-Purcell Meiboom-Gill (CPMG) pulse sequence, using a two second water pre-saturation time, consistently gave reproducible results. Resonances attributed to lactate were minimized under these processing conditions. Centrifugation speed and pre-saturation time did not affect the average line width; however, donor fasting state, processing temperature, and storage time did alter the line width. Most important, blood chemistry analysis revealed an inverse correlation between triglyceride levels and average methyl and methylene line widths. Thus, these factors alone caution against the indiscriminate use of proton NMR spectra to differentiate plasma from normal and cancer patients. PMID- 1897266 TI - [Infectious diseases in advanced age]. PMID- 1897264 TI - A comparison of Chinese traditional and Western medical approaches for the treatment of mild hypertension. AB - We compared the efficacy of Chinese traditional treatment for mild hypertension with that of a standard Western medical regimen in a group of 50 well-matched patients (24 allocated to Western medicine and 26 to Chinese traditional medicine) with mild hypertension (diastolic blood pressure 90-104 mmHg). Those receiving Western therapy were treated in a stepped-care fashion with dihydrochlorothiazide and atenolol. Those in the Chinese traditional therapy group received one of two mixtures of nine herbs and other ingredients, depending on symptoms at initial evaluation. Blood pressure dropped significantly in both groups after only a few days on therapy. After 19 days on treatment, the group receiving Western therapy had a fall in blood pressure from 168.2/96.3 mmHg to 137.3/76.7 mmHg (p less than 0.01), while those on Chinese traditional therapy fell from 168.2/95.9 mmHg to 146.4/80.5 mmHg (p less than 0.01). The fall in blood pressure was significantly greater, however, in those given Western therapy. The relief of existing symptoms or development of possible drug side effects was similar in both groups, except for nocturia, occurring more often in the group treated with Western therapy. We conclude that Western therapy is more effective in reducing blood pressure as compared with Chinese traditional therapy, but effective control of blood pressure in mild hypertensives is possible with either form of treatment. PMID- 1897267 TI - [Clinical significance of peptic erosions]. PMID- 1897265 TI - Measurement of the rate of aqueous humor flow. AB - Techniques which estimate the rate of aqueous flow generally require the use of tracer substances. Determination of the distribution of the tracer in the relevant body compartments permits calculation of the rate of flow within the limits of accuracy of the method used. The underlying theory, as well as the advantages and limitations of methods employing systemic, topical, intracameral, and intravitreal administration of tracer substances are reviewed. Since these methods all assume that the rate of aqueous secretion is constant, yet the presence of a diurnal rhythm of flow has been demonstrated in both rabbits and humans, a compartmental model of a circadian system based upon the vitreous depot technique is presented. This model estimates the degree to which a continuously changing rate of aqueous flow limits the ability to determine aqueous flow rate accurately by this particular method and illustrates this limitation, which is common to all tracer methods. PMID- 1897268 TI - [Early therapy of absolute tachyarrhythmia]. PMID- 1897270 TI - [Family status and coronary heart disease]. PMID- 1897269 TI - [The high risk patient (case report)]. PMID- 1897271 TI - [Use of alloarthroplasty in treatment of medial femoral neck fracture]. PMID- 1897272 TI - [Control of bovine dermatophytosis as a prerequisite for decreasing human occupational diseases in agriculture]. PMID- 1897273 TI - [Education of wound physicians in Saxony in the 18th century]. PMID- 1897275 TI - Ribonucleosides as minor milk constituents. AB - Ribonucleosides are minor milk constituents and show a typical pattern which is assumed to be species-specific. As well as the unmodified components adenosine, cytidine, guanosine, inosine, and uridine, modified compounds such as Nl methyladenosine and N6-carbamoylthreonyladenosine--products of the transfer RNA catabolism--have been identified and quantified in individual and bulk herd (race: German black pied) milk samples throughout a whole lactation period. The results of our longitudinal study have shown that--with the exception of the colostral phase--the levels of these minor constituents vary only slightly throughout lactation. These findings imply that ribonucleosides are useful for characterizing milk of different species and technological treatment. Ribonucleosides were determined and balanced, for example, in the course of the churning process, showing that the pattern of these minor milk constituents is useful as a "fingerprint" that allows differentiation between the three butter types defined in the German Federal Butter Ordinance. PMID- 1897274 TI - Postprandial plasma D-lactate concentrations after yogurt ingestion. AB - The risk of D-lactic acidosis after consumption of yogurt was investigated in seven healthy volunteers. After ingestion of yogurt containing 1.06 mmol/kg body weight, D-lactic acid postprandial plasma D-lactate concentrations increased from 0.070 +/- 0.020 to a maximum of 0.200 +/- 0.010 mmol/l within 60 min. That was half the maximum concentration after the equivalent amount of D-lactate in the form of an aqueous solution of DL-lactate. The shape of the postprandial plasma D lactate peak was flatter, but much broader after yogurt than after the aqueous solution, the peak areas being equal. When 0.64 mmol/kg body weight D-lactate were consumed as yogurt, plasma concentrations amounted to 0.086 +/- 0.030 mmol/l. Signs of a mild, transient, compensated metabolic acidosis, which was apparent in case of the aqueous lactic acid solution did not occur in case of yogurt. It is concluded that the consumption of foods containing D-lactic acid gives no reason for concern in healthy adults. PMID- 1897277 TI - Function of vitamin E in physical exercise: a review. AB - Even though vitamin E may not improve physical achievements in sports competitions, as shown in several swimming experiments, it is important for the health of skeletal muscle: in its role as the major lipid-soluble chainbreaking antioxidant in lipid cell membranes, vitamin E protects muscle tissue in aerobic exercise, in which oxygen metabolism and, consequently, free radical production are greatly accelerated. Animal studies in several laboratories have shown that endurance exercise results in the same type of oxidative muscle damage as does vitamin E deficiency: there is an increase in the peroxidation products pentane and malondialdehyde and in enzymes leaked from muscles to plasma. Oxidative tissue damage in vitamin-E deficient animals is exacerbated by endurance training and, conversely, it is reduced by high-dose vitamin E supplementation; also, preliminary studies in humans have demonstrated antioxidant protection by high dose vitamin E supplementation. After endurance exercise leakage of enzymes into the plasma and output of pentane in the breath were significantly reduced. During a high-altitude expedition in the Himalayas, protection was shown to be significantly better in the supplemented group than in the placebo group, as determined by anaerobic threshold and pentane exhalation. PMID- 1897276 TI - Comments on report of a joint FAO/WHO expert consultation on protein quality evaluation, Rome 1990. PMID- 1897278 TI - [The effect of dietary fats on the hemolysis resistance of the erythrocyte membrane during alimentary zinc and calcium deficiency in rats]. AB - In an earlier Zn-deficiency experiment (8) pair-fed-control rats surprisingly showed a 100% increased osmotic fragility of erythrocytes against hypotonic sodium chloride solutions. Because coconut fat, which is very low in essential fatty acids, was used, a deficiency of essential fatty acids was assumed. When the experiment was repeated the diet's coconut fat was replaced by sunflower oil (21% oleic acid, 69% linoleic acid). The erythrocytes of the animals with Zn deficiency showed an increase in osmotic fragility as against the control groups fed ad libitum. The data of the pair-fed control animals was in between those two groups and did not differ from the other two groups. Using sunflower oil instead of coconut fat decreased the osmotic fragility of the pair-fed animal's erythrocytes in opposition to the preceding experiment up to 100%. Additional Ca deficiency increased the osmotic fragility of the erythrocytes significantly in all three groups. When the Zn and Ca deficiency animals were repleted over 5 days on the basic diet the osmotic fragility of the erythrocytes was decreased significantly. The results show that the use of coconut fat in a restrictive diet causes essential fatty-acid deficiency. It ist also shown that the osmotic fragility of the erythrocytes depends partially on the status of Zn in dietary fat as well. PMID- 1897279 TI - [Behcet's syndrome. Possible differential diagnosis in multi-system symptoms]. AB - Behcet's syndrome was described as a triad with recurrent ulcers of the mouth, aphthae of the genitals as well as changes of the eyes. A fourth later added main criterion comprises multifarious dermatological symptoms. Facultative signs of a disease, which, however, occasionally may stand also in the centre of the clinical picture are vascular, gastrointestinal and central-nervous participations, arthritic pains and swellings as well as an epididymitis. On account of the infrequency of the disease outside the endemic regions and the development of the individual manifestations over larger periods it is often recognized very late. Out of the six casuistics described three of them fulfilled the criteria of a complete Behcet's syndrome with evidence of all four main criteria, in the remaining casuistics the incomplete clinical picture was present with three main and one to four side criteria. In all cases the course was relatively benign. Recently, streptococcal antigens were considered to be etiological factors; correlations with the HLA-system are ascertained for patients from endemic regions. In phases of clinical activity the combination of immunosuppressive agents with cortisonoids is the therapy of choice. PMID- 1897280 TI - [Psycho-rheumatic problems in patients with soft tissue rheumatism]. AB - Patients with non-articular rheumatism syndrome demand a multidimensional judgment and an interdisciplinary care in a biopsychosocial understanding of the disease. In the psychosomatic consideration factors from the person-environment interaction of the patient gains increasedly importance. Thereby the communication of pain in the doctor-patient relationship and the valuation of pain in the family play a particular role. These regions of psychorheumatological problems are shown and discussed. PMID- 1897281 TI - [Nutrition and primary osteoporosis]. AB - Osteoporosis is a bone disease of great sociomedical and economic importance. Postmenopausal women are primarily affected. Pathogenesis is of multifactorial origin. In Western countries, reduced physical activity and an inadequate nutritional calcium supply are important aspects besides decreased postmenopausal oestrogen secretion. Food statistics confirm that in the Federal Republic of Germany calcium intake is below the DGE recommendation in almost all age groups, especially in women. Calcium may play a role in prevention of osteoporosis. The paper reports on individual measures to enhance calcium intake. Furthermore, the influence of the postmenopausal status on calcium metabolism and calcium requirement is demonstrated. Finally, the importance of other nutritional aspects for the manifestation of osteoporosis is discussed. PMID- 1897282 TI - [50 years ago: documentation of the Bernburg "euthanasia" action program (II)]. AB - The history of the "euthanasia" action programme began at Bernburg in 1940 and finished in 1943. It passed under regional peculiarities. In this second part of the report the organisational details of criminal actions were analysed and additionally the development of the physicians who took part in. PMID- 1897283 TI - [Evaluation of a weight reduction program: slender without diets]. AB - "Schlank ohne Diat" ("Weight-Reduction Without Diet") is a strategy to normalize body weight, by influencing multiple factors that appear to influence and promote obesity. The base line of therapy is the modification of nutritional habits. Self control, especially monitoring and recording of calorie intake and the loss of energy by physical activities is the key that trains every client to change his nutritional habits and helps to reduce body weight and keep normal body weight stable. In a retrospective study, including 134 persons, 84 clients (62,69%) were able to reduce body weight, 9 clients (6,72%) reached starting point of weight and in 30,60% (41 clients) during the participation in this methods an increase of body weight was seen. On an average 120 clients achieved a weight reduction of 5.98 kg during the participation in this method. The loss of weight ranged from 1 to 31 kg per person. PMID- 1897284 TI - [Therapy of HIV infection (AIDS)]. AB - The stages of human immunodeficiency viruses (HIV) life cycle are described as guide to therapeutic intervention. Practical therapeutic recommendations are given. They should be directed to viruses as the causal agent and to the features of opportunistic infections as well as of associated malignant tumors. Recently 3 progresses could be reached: (1) the application of azidothymidine in the latency phase, when the number of CD4 positive cells decreases below 500/mm3, whereby the progression of the disease can be delayed and side-effects can be reduced; (2) the prophylaxis of pneumocystis carinii pneumonia by inhalation of pentamidin; and (3) the introduction of fluconazole acting against yeast fungus infection, whereby development of resistant yeast strains is still missing and side-effects are smaller than with other antimycotics. In addition, the application of HIV vaccine in already HIV-infected persons seems to be effective. By combining several drugs their toxicity is to be reduced. Interdisciplinary research and good cooperation among clinicians are conditions for an effective therapy. Last but not least psychosocial aspects and a good psychological guidance and counseling of the affected persons should be considered. PMID- 1897285 TI - [Use of light reflex rheography in diagnosis of chronic venous diseases]. AB - The light reflexion rheography is described as non-invasive investigation method for the venous system. The basic principle of the method and its applications are explained as well as its evaluation and the peculiarities which are to be taken into consideration thereby are discussed in detail. The comprising evaluation of the haemodynamic changes in chronic diseases of the veins is particularly elucidated by the method with regard to an improvable chronic venous insufficiency and to the differentiation between epifascial and subfascial pathological changes on the venous system. The method is suitable for the differentiation of the possible forms of therapy as well as for the examination of the result of the treatment. By means of this method a judgment of the efficacy of preparations for vein diseases is not possible. At the earliest the technique is comparable with the bloody measurement of the venous pressure phlebodynamometry. Its smaller exactness should be compensated by triple measurement. The possibilities of errors as well as the advantages of the method and its areas of application preferred are discussed in detail. The light reflexion rheography is nowadays together with the ultrasound Doppler diagnostics a technique of diagnostics which should be present in every phlebologic practice. PMID- 1897286 TI - [Pharmacokinetic aspects of tuberculosis therapy with a fixed combination of rifampicin, isoniazide and pyrazinamide]. AB - The here described investigations show correspondingly that the administration of isoniazid, rifampicin and pyrazinamide in a fixed combination of the administration of the individual substances is bioequivalent under pharmacokinetic aspects. Further investigations on large populations of patients must, however, still confirm whether or not the advantages of the fix combination striven for or theoretically to be expected can be proved in practice. PMID- 1897287 TI - [Systolic time intervals and echocardiography in monitoring adriamycin-treated tumor patients]. AB - By means of systolic time intervals (PEP/LVET) and echocardiography (Vfr) 218 tumour patients were controlled concerning a cardiomyopathy induced by cytostatic agents. 13% of the patients (28/218) transgressed an absolute cumulative dose of 1,000 mg of doxorubicin or daunorubicin, of which, however, 12% (26/218) showed normal values for PEP/LVET. 11% of the patients (24/218) showed pathologic PEP/LVET values in 6% (49/787) of the investigations, in which case in 15 patients the clinical diagnosis of a cardiomyopathy could be assumed with simultaneously decreased shortening fraction. The sex and age distribution of this group corresponded to that one of the total cohort. The investigation presented confirm the value of systolic time intervals and of echocardiography as screening methods for a cardiomyopathy and speak against a general establishment of a borderline diagnosis. PMID- 1897288 TI - [200 years ago: special medical degrees in the 18th century exemplified by Halle]. AB - The taking of a medical doctor's degree in the 18th century differed considerably from that one of our days. At the example of the Faculty of Medicine of Halle University the courses of the regular proceeding are described including the legally possible modalities of graduation. The taking of the degree of honorary doctor were included into the series of particular graduations which took place under highly different prerequisites. PMID- 1897289 TI - [Diagnosis of genetically determined diseases]. AB - Enzymopathies of pyruvate kinase are caused by defects of structural genes forming stable and unstable mutants, respectively. Stable mutants of PK are characterized by high S0,5 PEP and nearly unchanged Vmax. A decrease of PEP affinity can be the result from a very high allosteric constant L0 or from an increased KPEP. From the pattern of PAGE can be concluded that stable PK mutants are tetraheteromers composed of two normal and two shortened polypeptide chains. We suppose that this is the result of a mutation of a codon which stops the polypeptide synthesis of PK earlier. Most PK mutants are unstable. They are characterized by low catalytic activity and high PEP affinity. The kinetic properties of unstable mutants are changed posttranslational by proteolytic modifications. Furthermore low S0,5 PEP values result from a persistence of the isoenzyme PK-K in reticulocytes and erythrocytes, respectively. A prenatal diagnosis of PK enzymopathies can be carried out with a very small blood volume by using the method of isoelectrophoretic focussing. PMID- 1897290 TI - [Pathobiogenetic concept of Duchenne muscular dystrophy following the discovery of dystrophin as the deficient protein]. PMID- 1897291 TI - [Clinical significance of serum concentration of connective tissue components in cases of organic fibroses]. PMID- 1897292 TI - Pediatric emergency laboratory. AB - The laboratory contribution in the care of a seriously ill child is essential to plan and organize the therapy after the first-step emergency care and to know the aethiology of the illness. The most acute syndromes in pediatric emergency care are: coma, convulsions, dehydration, metabolic disequilibrium, hypovolemic or anaphylactic shock, serious infectious diseases and chemical or drug poisoning. The laboratory tests which have to be available within few minutes are blood cell count, hemogasanalysis, sodium, potassium and calcium, glucose. Total proteins, serum creatinine and urea, bleeding tests, blood smear, sedimentation rate, ALT, AST, osmolality, urinary electrolytes and creatinine and cerebrospinal fluid examination should be available within sixty minutes. New accurate and rapid techniques and instrumentations make easier the diagnostic and therapeutical approach to pediatric emergency. PMID- 1897293 TI - [Immunologic determination of albumin the feces as evidence of hemorrhage in the colon]. PMID- 1897294 TI - [Agent-conditioned influence on carbohydrate metabolism and energy state in liver and lung of rats in endotoxic shock]. AB - The pretreatment of rats with the substance LPH and LXU caused decrease of lethality in endotoxin shock and suppression of the following changes 6 hours post endotoxin: Increase of plasma ICDH activity, decrease in platelet count, decrease of the hepatic energy state and increase of the ATP content in the lung. The catabolic glucose metabolism during endotoxin shock was not influenced by LPH and LXU administration. PMID- 1897296 TI - Application of the monodimensional electrophoresis for the separation of glycosaminoglycans on Cellogel cellulose acetate strip. AB - A monodimensional electrophoretic method for the separation of glycosaminoglycans on Titan III Zip Zone cellulose acetate plate based on their different electrophoretic mobilities in barium acetate and different solubilities in ethanol was applied to the Chemetron electrophoretic equipment. Improved timing of individual steps of electrophoretic run, additional cooling and pressure must be introduced for optimal separation of glycosaminoglycans mixture (dermatan sulphate, heparan sulphate, hyaluronic acid, chondroitin-4-sulphate, chondroitin 6-sulphate and keratan sulphate) resulting in five well separated sharp bands. By all these changes in the original procedure of Hopwood and Harrison, the separation of chondroitin-4-sulphate and chondroitin-6-sulphate was not achieved. The modified procedure on Cellogel strip is suitable for the screening of mucopolysaccharidoses. PMID- 1897295 TI - [Isoelectric focusing of pure human pancreatic juice. 2. Identification of enzymes and proenzymes and characterization of glycoproteins]. AB - After isoelectric focusing of proteins of human pure pancreatic juice following digestive enzymes and zymogens were identified by substrate specific detection methods: in the anodic range trypsinogen 1, and acidic form of proelastase and procarboxypeptidase A; in the pH--range of 5.0-6.0 a trypsinogen--like protein and the secretory trypsin inhibitor; in the pH--range of 6.0-7.0 one form of each of procarboxypeptidase B, trypsinogen 2, lipase, chymotrypsinogen and two forms of alpha-amylase and in the cathodic range an activated form of procarboxypeptidase B, one form of prophospholipase A2 and an additional form of proelastase. In order to characterize glycoproteins the IEF separated pancreatic proteins were transferred onto nitrocellulose membranes. Using the periodic acid/Schiff's reagent (PAS) procedure five PAS-positive proteins (pl s 4.5; 6.0; 6.6; 6.9 and 7.3) were detected. Three Con A-binding proteins (pl s 6.0; 6.6 and 6.9) were identified by incubating the blot in Con A followed by peroxidase and o phenylendiamin as a chromogenic peroxidase substrat. PMID- 1897297 TI - [Sialic acid--an acute phase reactant and a concomitant of tumors]. AB - Sialic acid is an acute phase reagent with tumour burden reflecting fluctuations of serum level. The parameter is unsuitable for an early recognition of cancer. Sialic acid could be used as a parameter in questions concerning tumour burden: the diagnosis of tumour stage, the control of growth after therapy, the prediction of recidivation. The small specificity of an increased serum level of sialic acid will presumably be only of little use in tumour diagnostics. PMID- 1897298 TI - [Determination of neopterin by a commercial radioimmunoassay in aortocoronary bypass surgery and heart transplantation]. AB - On the hand of a small number of patients with coronary bypasses the influence of heart-lung-machine-operations on the neopterin level in blood, generally used for the detection of rejected heart transplants, is investigated. The results suggest, that the Neopterin level is not affected by the surgical attempt. PMID- 1897299 TI - [Use of a computer in a clinical-toxicological laboratory with a fuzzy search]. AB - If a clinician is faced with acute intoxications a rapid toxicological test is essential. The toxic substances are identified by a combined use of various systems of analysis such as gas chromatography, thin-layer chromatography or UV spectroscopy. As the result of the analysis a data pattern is obtained which can be interpreted by comparing it with substance-related reference patterns. This paper describes a computer-program which allows more efficient reference comparisons and which gives a support of the decisions. The algorithms of the comparisions are based on fuzzy-theory. PMID- 1897300 TI - [Biofreezer BF 80--a universally employed apparatus in preservation at very low temperatures]. AB - A computer-controlled freezing apparatus is described which uses liquid nitrogen (LN2) as coolant. The freezing equipment BF 80 consists of a big cryochamber (volume 24 l), a LN2 tank and a computer for the control of the freezing procedure. The biofreezer functions in the range from 40 to -180 degrees C. A complete cooling curve can be composed of up 15 linear segments with freezing rates between 0 and 45 K.min-1. In the computer up to 80 different freezing curves can be stored and activated by simple operations. The reliability of the biofreezer BF 80 was successfully tested for the cryopreservation of lymphocytes. PMID- 1897301 TI - [An average variation for glucose determination using the ECA 20]. PMID- 1897302 TI - [Measruement of capillary blood using the Coulter S Plus VI, the Coulter T660 and the Coulter T890]. PMID- 1897303 TI - Human response to a malaria vaccine candidate antigen. AB - The Plasmodium falciparum heat-shock protein 70 (PFHSP70) has been proposed as a potential candidate antigen for a malaria vaccine. In this study the human immune response to this antigen has been evaluated. Enzyme-linked immunosorbent assays (ELISA) were performed on serum samples collected from individuals during and after malarial infection. Only 70% of falciparum malaria patients responded to this antigen during the natural course of infection and 54% of the recovered cases who had no parasitaemia at the time of blood collection lacked detectable antibody. The non-responders to PFHSP70 exhibited an antibody response to total schizont antigens. There was no correlation between the response against total schizont antigens and PFHSP70 antigen. The non-responsiveness against PFHSP70 was not related to age, sex or regional variations. These qualities are undesirable for a vaccine candidate antigen. PMID- 1897304 TI - Principles of selective inactivation of viral genome. VII. Some peculiarities in determination of viral suspension infectivity during inactivation by chemical agents. AB - When the infectivity of the influenza virus is determined by means of titration on chicken embryos, calculating the infection titre according to Reed and Muench, the course of inactivation with beta-propiolactone shows an anomaly - the fraction of infected embryos in a batch initially increases and then decreases as the degree of dilution of the virus-containing sample is increased. This anomaly occurs because a slight dilution lowers the agent concentration insufficiently so that inactivation goes on after the dilution of the sample before and/or after the inoculation of the solution into the embryo. The anomaly can be avoided either by neutralizing or removing the agent prior to titration or by starting titration from high dilutions. PMID- 1897306 TI - Circulating diphtheria antitoxin levels in children aged 11-14 years in relation to the vaccinal history. AB - Diphtheria antitoxin level in serum samples obtained from 204 healthy children aged 11-14 years was determined by means of an indirect haemagglutination technique and related to the vaccinal history of the subjects. Irrespective of the time since the last toxoid inoculation, the mean antitoxin titre per ml of serum in the individuals who had received incomplete/irregular anti-diphtheria vaccination in childhood was significantly higher when the number of toxoid doses was higher (from two to more than four doses); the same was not observed for individuals given primary vaccination (three toxoid doses) according to the schedule for childhood vaccination in Italy (regular vaccinees) and one or more booster doses. Between 8 and 13 years after the last of three toxoid doses, a significantly negative association between mean antitoxin titre and time was observed only in irregularly vaccinated children (r = -0.82; p less than 0.05); nevertheless, up to thirteen years after the last vaccine dose, more than 95% of the children exhibited protective levels of antitoxin (greater than 0.125 turkey red blood cells passive haemagglutination units per ml). No significant decrease in mean antitoxin titre was observed between 4 and 10 years after the last of four either regularly or irregularly administered toxoid doses. PMID- 1897305 TI - Characterization of the attenuating M and NP gene segments of the avian influenza A/Mallard/78 virus during in vitro production of avian-human reassortant vaccine viruses and after replication in humans and primates. AB - A unique requirement for live attenuated reassortant influenza vaccines is the need to generate new reassortant vaccine viruses with the appearance of each new antigenic variant. Thus, the attenuation phenotype conferred by the attenuated donor influenza virus must remain genetically stable during the generation of each new reassortant vaccine virus. In this study we used nucleotide sequence analysis to evaluate the genetic stability of the attenuating M and NP genes of the avian influenza A/Mallard/NY/6750/78 attenuated donor virus during the in vitro generation and subsequent in vivo replication of avian-human (AH) influenza A reassortant vaccine viruses in monkeys and humans. Nucleotide sequence changes in the M and NP genes occurred at a rate of approximately 0.61 substitutions/1000 nt/reassortant during in vitro generation of four AH reassortant viruses. Only two nucleotide sequence changes occurred in the M and NP gene segments of four isolates of H1N1 or H3N2 AH vaccine viruses following 6-8 days of replication in seronegative children, and neither change affected amino acids previously identified as playing a potential role in attenuation. In addition, there were no changes in the nucleotide sequence of the M and NP genes of single gene AH reassortant viruses following five serial passages in squirrel monkeys. Finally, there was no change in the level or duration of replication of the single gene reassortant viruses in the upper or lower respiratory tract of monkeys following serial passage.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1897308 TI - Poliomyelitis vaccination: the essential booster. PMID- 1897307 TI - Comparative trial of administration of half (0.05 mg) and quarter (0.025 mg) dose of intradermal Pasteur BCG on 291 infants from birth to 1 year in French Guyana. AB - The study concerns 291 newborns and infants aged 0 to 1 year placed randomly in two groups which respectively received 0.025 and 0.05 mg Pasteur BCG by intradermal injection, between 1 December 1988 and 28 February 1989. This random test aimed to determine if the administration of one quarter dose (0.025 mg) of intradermal BCG conferred immunity comparable to that of one half (0.05 mg) while diminishing the risk of complications, in particular suppurative adenopathy, in infants of ages 0-1 year. Statistical analysis of the results showed that the 0.025 mg dose of intradermal BCG entails an immunoresponse as satisfactory as that entailed by the 0.05 mg dose, while the rate of suppurative adenitis is significantly higher in the group that received the 0.05 mg dose. It is therefore well justified to recommend a dose of 0.025 mg of intradermal Pasteur BCG for infants aged 1 year and less. PMID- 1897309 TI - [Succession in the morphological organization in human postnatal ontogeny]. AB - Preserving morphological organization succession in the human postnatal ontogenesis is studied in the growth processes in 7-17 years old boys. Canonical variables are separated by canonical correlation method, which are those maximally correlated morphological structures relating to each other hierarchically: body--head, body trunk--limbs, brain--face. It is shown that morphological organization succession is provided by preserving the stable level of interdependence between morphological structures, which are under relatively independent genetical control. The stability of this interdependence in disturbed only during the "critical phase" of adolescent spurt, which is characterized by maximal rate of morphofunctional development. After this phase initial level of the interdependence is restored. PMID- 1897310 TI - Simultaneous expression of the S and L surface antigens of hepatitis B, and formation of mixed particles in the methylotrophic yeast, Hansenula polymorpha. AB - An expression system has been developed for the methylotrophic yeast Hansenula polymorpha and used to co-express both the L (preS1-S2-S) and S hepatitis B surface antigens (HBsAg) under the control of strong methanol-inducible promoters derived from the methanol oxidase and from the formate dehydrogenase genes. A unique feature of this H. polymorpha expression system is the possibility of integrating up to 100 copies of an expression cassette via a multimeric integration mechanism. Several multimeric integrants containing various numbers of L and S expression cassettes were constructed to give a spectrum of strains characterized by different L to S ratios. The expression level of S antigen was 5 8% of the total soluble cell protein. Analysis by sucrose and CsCl density gradient centrifugation and by particle-specific immunoassays demonstrated that the synthesized HBsAg spontaneously assembled into composite subviral particles containing both S and L proteins. Only a minor portion of the L protein was found to be glycosylated. These H polymorpha-derived composite particles can be used for the production of a hepatitis B virus vaccine with the potential for improved immunogenicity due to the presence of a wider spectrum of epitopes and negligible glycosylation. PMID- 1897311 TI - Analysis of the expression and secretion of the Candida tsukubaensis alpha glucosidase gene in the yeast Saccharomyces cerevisiae. AB - The alpha-glucosidase gene of Candida tsukubaensis is contained within a 3.47 kb BamH1-Mlul fragment which, when introduced into Saccharomyces cerevisiae AH22 on a yeast-Escherichia coli shuttle vector, allows the transformants to utilize maltose as sole carbon source. Thus, the cloned gene confers a dominant selectable phenotype on transformed strains of S. cerevisiae which are otherwise unable to grow in nutrient media containing maltose, dextrin or other alpha-1.4 linked alpha-D-glucopyranosides, specifically hydrolysed by the alpha glucosidase. The cloned enzyme expressed in yeast is secreted into the extracellular medium in a glycosylated form which accounts for up to 60% of the secreted protein and has a molecular size of 70-80 kilodalton (kDa). Deglycosylation of the alpha-glucosidase showed that the enzyme is composed of two distinct polypeptides with subunit molecular weights of 63-65 kDa (peptide 1) and 50-52 kDa (peptide 2). An increase in the level of expression of the alpha glucosidase by yeast transformants in selective minimal medium was obtained by using a vector with increased copy number containing the leu2-d gene as selectable marker. The alpha-glucosidase gene promoter functions more effectively than the Gall-10 promoter in directing alpha-glucosidase expression in S. cerevisiae. It also directs the expression of high levels of beta-galactosidase activity in yeast when fused to a promoterless E. coli lacZ gene. Expression of the alpha-glucosidase gene under the control of its own promoter is constitutive, orientation dependent and not subject to catabolite repression. PMID- 1897312 TI - Glucan structure in a fragile mutant of Saccharomyces cerevisiae. AB - The phenotype of VY1160 fragile Saccharomyces cerevisiae mutant is characterized by cell lysis upon transfer to hypotonic solutions and increased permeability of cells growing in osmotically stabilized media. Two mutations, srb1 and ts1, have been identified in VY1160 cells and previous studies have shown that the increased permeability is due to the ts1 mutation which causes a shortening of mannan side-chains. Here we report that the srb1 mutation, which is the genetic determinant of cell lysis, is responsible for quantitative and structural changes of glucans. Experiments with isogenic single mutation strains, genetic studies coupled with quantitative measurements of glucan content per cell, and methylation analysis of glucans provide evidence that srb1 mutation leads to i) formation of mechanically unstable cell wall network made of insoluble glucan fibrils which are shorter and contain beta(1-6) inter-residue linkages and ii) insufficient filling of the space between the fibrils due to a shortage of the alkali-soluble glucan. Although growing exponentially in osmotically stabilized media, the srb1 cells cannot resist an osmotic shock and, hence, burst immediately. PMID- 1897313 TI - The YDp plasmids: a uniform set of vectors bearing versatile gene disruption cassettes for Saccharomyces cerevisiae. AB - The YDp plasmids (Yeast Disruption plasmids) are pUC9 vectors bearing a set of yeast gene disruption cassettes, all uniform in structure and differing only in the selectable marker used (HIS3, LEU2, LYS2, TRP1 or URA3). The markers, surrounded by translational termination codons, are embedded in the slightly modified sequence of the pUC9 multiple cloning sites. PMID- 1897314 TI - Incorporation of unsaturated fatty acids by Saccharomyces cerevisiae: conservation of fatty-acyl saturation in phosphatidylinositol. AB - Saccharomyces cerevisiae was grown anaerobically in media supplemented with myristoleic 14:1(9c), palmitoleic 16:1(9c), oleic 18:1(9c), linoleic 18:2(9,12c), gamma-linolenic 18:3(9,12,15c) or eicosenoic 20:1(11c) acid. Cells from exponential-phase cultures contained approximately the same proportions of the major phospholipid classes, namely phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol and phosphatidylserine, the greatest differences being detected in cells grown in the presence of 14:1(9c) or 20:1(11c) acids. The extent to which phospholipids from cells were enriched with residues of the exogenously supplied acid varied from 52% in cells grown in the presence of 14:1(9c) acid to 13% in cells grown in media supplemented with 20:1(11c) acid. Analysis of the fatty-acyl composition of the four major phospholipid classes revealed that the degree of unsaturation varied considerably in three of the classes, while phosphatidylinositol conserved a high degree of saturation. The possible significance of the latter finding in relation to the physiological role of phosphatidylinositol in the plasma membrane is discussed. PMID- 1897315 TI - Assignment of most genes encoding major peroxisomal polypeptides to chromosomal band V of the asporogenic yeast Candida tropicalis. AB - The peroxisomes of the asporogenic yeast Candida tropicalis contain about 20 major polypeptides (PXPs). We have isolated a number of genes encoding them; 11 POX genes encoded independent PXPs and three POY genes were likely to encode three other PXPs. To locate these genes on the chromosomes, chromosomes of C. tropicalis were separated by pulsed-field gel electrophoresis. Eight chromosomal bands were observed over the range of 1.0 Mbp (band 1) to 2.8 Mbp (band VIII); the genome size was estimated to be about 20 Mbp. Southern blot analysis showed that ten genes were on band V, three genes were on band IV, and the other gene was on band VI. Three genes gave hybridization signals of nearly equal intensity on two different chromosomal bands: POX6A and POX8B, on bands V and VII; and POX8A, on bands IV and VI. Ribosomal RNA genes also hybridized to two bands, VI and VII. Most genes assigned to only one band hybridized to two restriction fragments produced by either NotI or SfiI endonuclease. The results suggested that C. tropicalis was diploid and that restriction sites were conserved little between homologues. The three POX genes that were found on two chromosomal bands hybridized to not more than two restriction fragments, implying that the allelic genes were present on different chromosomal bands. PMID- 1897316 TI - Genetic transformation of auxotrophic mutants of the filamentous yeast Trichosporon cutaneum using homologous and heterologous marker genes. AB - A transformation system for the filamentous yeast Trichosporon cutaneum based on auxotrophic markers is presented and techniques for the induction, isolation and characterization of mutants are described. A number of auxotrophic mutants were isolated and characterized by using biosynthetic precursors and/or inhibitors. A mutant unable to grow in the presence of ornithine could be complemented successfully by spheroplast transformation experiments using the cloned Aspergillus nidulans ornithine transcarbamoylase gene (argB gene) as selection marker with an efficiency of 5-100 transformants per microgram of DNA. In these transformants the heterologous argB gene was present in multiple tandem copies and the transforming DNA was found to remain stable after more than 50 generations in non-selective media. The same mutant could be complemented by a T. cutaneum cosmid gene library and a complementary cosmid was subsequently isolated from this library by a sib-selection strategy. This cosmid transformed T. cutaneum spheroblasts with an efficiency of 50-200 colonies per microgram of DNA. Southern blot analyses were consistent with the view that the transforming sequences became stably integrated into the host genome at the homologous site. PMID- 1897317 TI - Isolation and characterization of Schizosaccharomyces pombe mutants lacking aminopeptidase activity. AB - A mutant strain of the fission yeast Schizosaccharomyces pombe defective in aminopeptidase I was isolated by screening for lack of activity against the chromogenic substrate lysine-beta-naphthylamide in isolated colonies. Tetrad dissection of sporulated diploids heterozygous for the wild-type and mutant allele resulted in a 2:2 segregation of mutant and wild-type phenotype indicating a single chromosomal gene mutation. Gene dosage experiments indicated that the mutation might reside in the structural gene of aminopeptidase I. No vital consequences of aminopeptidase I deficiency on cell life and sporulation could be detected. However, the enzyme seems to be involved in protein degradation under conditions of nutrient deprivation. PMID- 1897319 TI - [Evolutionary physiology in the Institute of Experimental Medicine (on the centenary of its founding)]. PMID- 1897318 TI - The complete sequence of a 11,953 bp fragment from C1G on chromosome III encompasses four new open reading frames. PMID- 1897320 TI - [The ultrastructural characteristics of the motor neuron synaptic organization in the spinal cord of the frog Rana ridibunda]. AB - Electron microscopic studies on the spinal motor nuclei in amphibians indicate significant diversity in chemical synapses formed on motoneurones by axonal endings of supra- and intraspinal systems. High ultrastructural specialization was observed among axosomatic, axodendritic and axoaxonal synapses. Several types of axo-spine synapses and axodentritic synaptic complexes of the "glomerular" type were revealed. New data on ultrastructural peculiarities of chemical synapses presented in this paper, together with earlier detailed data on morphologically mixed and electrotonic synapses, increase our knowledge of evolutionary trends in synaptic organization of motoneurones in the spinal cord and suggest the existence of a complex mechanism of integration of synaptic influences in the spinal cord of lower vertebrates. PMID- 1897321 TI - [The inotropic action of acetylcholine on the heart ventricles during larval development in the frog Rana temporaria]. AB - The effects of acetylcholine and other cholinergic drugs on the isolated electrically driven larval frog ventricles have been studied. The negative inotropic response to acetylcholine appeared as early as stage 33 of the larval development (the stages were determined according to Dabagian and Sleptsova, 1975) and persisted through all the developmental stages including metamorphosis. The response is muscarinic in origin since it was reproduced with a muscarinic agonist methylfurmetide, blocked with atropine but was not modified with tubocurarine. At the stage 41 and following stages, the sensitivity to acetylcholine was decreased while to methylfurmetide was not. The decreased sensitivity to acetylcholine is most likely due to increase of activity of cholinesterases in the myocardial tissues. PMID- 1897322 TI - [The summation properties of the somatosensory system demonstrated via a study of the tactile sensations evoked by an electrical current and by focused ultrasound]. AB - Sensational thresholds of the skin of fingers, palm and forearm have been determined in 5 healthy subjects ageing from 20 to 49 years. About 100 summation curves were obtained. Critical duration of the electrical stimuli remained constant in various areas. Critical duration of ultrasonic stimulation increased from fingers to forearm. The data obtained together with those found in literature suggest that critical duration of the stimulus is associated with the diameter of nonmyelin nervous fibers which are affected by the stimulus increasing with the increase in fiber diameter. PMID- 1897323 TI - [Fractures of the tibial head. Classification, diagnosis, therapy (review)]. PMID- 1897324 TI - [Non-cemented alloplasty of the hip joint]. AB - The authors present a review of the contemporary problem of non-cemented alloplasty of the hip joint. They compare the advantages and disadvantages of cemented and non-cemented endoprostheses of the hip joint in relation to possible loosening and possible re-operation and with regard to the surgical technique. The negative action of bone cement is divided into two groups: 1. immediate effects which act on surrounding tissues and the patient's organism during operation. 2. late effects which involve abrasion and the phagocytic response to small cement fragments and the formation of osteoaggressive granulations. These late effects are demonstrated on histological material. The authors emphasize that non-cemented alloplasty has also some pitfalls which involve in particular higher demands on the accuracy of the surgical technique and, no doubt, more severe haemorrhage. The main advantages are according to the authors the elimination of negative effects of bone cement, in particular late effects. The authors tried to classify the contemporary spectrum of available non-cemented implants with regard to their design, materials and surface finish. PMID- 1897325 TI - [Initial experience with the closed method of subcapital osteotomy of the 1st metatarsus in hallux valgus]. AB - The authors summarize initial findings with Bosh's modification of Hohmann's subcapital osteotomy made by means of a cutter from a short dermal incision under X-ray control. The valgosity and rotation of the hallux are corrected by a lateral and possibly plantar shift and by derotation of the head of the metatarsus. The position of the head is ensured by supporting the medial exostosis by a wire inserted by the intramedullary route into the Ist metatarsus. The operation was performed in five female patients aged 37-60 years on nine feet. The results were evaluated after 10-13 months. For osteotomy conic cutters were used (diameter of base 2.1 mm and 5 mm) and a drill (3000 rotations per minute) from the small instrumentarium of SYNTHES Co. The Kirschner wire was removed after four weeks and fixation a with a plaster spica of the toe took, depending on healing, 7-12 weeks after operation. In all instances marked correction of the position of the toe occurred (reduction of the valgosity angle by 8-19 degrees). As to subjective evaluation, four patients evaluated the result as excellent, three as satisfactory, i.e. disappearance or marked reduction of complains and once as unsatisfactory with persisting pain and difficulties as regards footwear. After analysis of the first early results the authors recommend to indicate the operation in valgosity of the toe up to 35 degrees and minimal arthrosis, to perform the osteotomy in a strictly subcapital and extracapsular position and to reduce the period of fixation. The advantage of the method is that the metatarsophalangeal joint is not damaged, the operation is sparing, marked correction of the position of the toes is achieved, the time of operation is short and the scar is not visible. PMID- 1897326 TI - [Surgical treatment of sequelae of injuries of the thoracolumbar spine]. AB - The authors describe surgical techniques used in 48 patients with sequelae of injuries of the thoracolumbar spine and the achieved results. Twenty-one patients were treated by an anterior operation, 14 by posterior operation and 13 a combination of both. The anterior operation involved 1) simple stabilization by autografts or 2) release, correction of the kyphosis and fusion and 3) elimination of the affected body of the vertebra and replacement by a massive allograft. If reliable stability was not achieved, instrumentation was added. In posterior operation they always stabilized the spine by instrumentation and added fusion. In the remaining patients they combined the posterior and anterior operation. The anterior operations were, if necessary, supplemented by decompression, when using the posterior approach they decompressed by the posterolateral route. As to complications which called for re-operation, instrumentation failed once and twice a pseudoarthrosis was repaired. Pain disappeared or receded substantially in 86%. Of 30 patients with a partial nervous lesion 14 (47%) improved, in two slight deterioration occurred. PMID- 1897327 TI - [Sequelae of injuries of the thoracolumbar spine and indications for surgery]. AB - Inadequate treatment of a fresh injury of the thoracolumbar spine of failure or surgical treatment may lead to substantial restriction of the physical activity of the patient. This is due to posttraumatic kyphosis, possibly its progression, instability, painfulness and a persisting or progressing neurological finding. Forty-eight patients with unstable fracture of the thoracolumbar spine were, except one operated patient, treated originally by conservative methods, 15 of them were moreover subjected to isolated laminectomy. In 30 patients a partial nervous lesion was involved. The majority of patients in the group subjected to laminectomy had a more severe kyphotic deformity which more frequently was progressive. The authors indicated surgery in 18 patients (37%) on account of pain, in 14 (29%) on account of instability, in 12 (25%) on account of progressing kyphosis and in 4 (8%) on account of an increasing nervous deficit. They included 26 patients with persisting partial nervous affections in the group with instability and progressing kyphosis, as anterior compression of the dural sac was revealed and they indicated release of nervous structures as part of the surgical operation. In the remaining partial neurological lesions with a patient spinal canal decompression was not indicated. PMID- 1897328 TI - Growth hormone specific stimulation of mitosis by size-fractionated serum from patients with growth hormone insufficiency: a study on the rat lymphoma cell line, Nb2. AB - The aim was to investigate the bioactivity of a high-molecular weight human growth hormone, identified following molecular sieve chromatography of serum. Nine patients with pituitary disease and GH insufficiency were studied. All patients had non-detectable levels of immunoreactive GH, less than 0.2 micrograms/l, in diurnal serum profiles. GH bioactivity was determined before and after size-fractionation of serum. The bioassay is based on the finding that a rat lymphoma cell line, Nb2, proliferates in the presence of lactogens. GH and PRL immunoreactivities were measured by radioimmunoassays. Pronounced GH immunoreactivity was found in fractions of sera from 7 out of the 9 patients and of 2 of 4 control sera, particularly in fractions corresponding to the elution volume of high-molecular weight proteins (greater than 160 kD). PRL immunoreactivity was only detected in fractions corresponding to the elution volume of monomeric PRL. Unfractionated serum had a dose-dependent mitogenic effect on the Nb2 cells. GH-antibodies could not inhibit this effect. Fractions of serum obtained from the patients stimulated Nb2 cell division as well. The mitogenic effect of serum fractions could be inhibited by GH-antibodies. Thus, high-molecular weight GH circulating in patients with GH insufficiency were shown to exert a GH-specific bioactivity in vitro after size-fractionation. PMID- 1897329 TI - Circulating levels of calciotropic hormones during treatment with nasal salmon calcitonin. AB - Circulating levels of calciotropic hormones were measured during one year of treatment with either 200 IU of salmon calcitonin daily or placebo as a nasal spray in 20 postmenopausal women with a former Colles' fracture. A supplement of 0.5 gram elemental calcium was given to all participants. Serum levels of parathyroid hormone and human calcitonin were determined with radioimmunoassays, and serum levels of vitamin D metabolites were determined with protein binding assays. We did not find any significant differences between the two groups with respect to serum levels of calciotropic hormones. In the salmon calcitonin treated group there was a tendency towards a small decrease in serum levels of human calcitonin and an increase in serum levels of calcitriol. Our results suggest that treatment with 200 IU of salmon calcitonin daily as a nasal spray does not markedly affect fasting serum levels of parathyroid hormone, human calcitonin, and vitamin D metabolites. PMID- 1897330 TI - Spontaneous anovulation causing disappearance of cyclical symptoms in women with the premenstrual syndrome. AB - In the premenstrual syndrome the negative symptoms appear during the luteal phase of the menstrual cycle. Ovulation and the formation of a corpus luteum seem to be of great importance in precipitating the syndrome. In a large group of women with premenstrual syndrome investigated daily with symptom ratings and weekly plasma estradiol and progesterone assays, 8 were found to have one ovulatory and one spontaneously occurring anovulatory menstrual cycle. In both these cycles, the post- and premenstrual phases were compared by testing for recurrence of symptoms. All patients showed a highly significant cyclical worsening of negative premenstrual symptoms during the ovulatory cycles, whereas in the anovulatory cycles the cyclical symptoms disappeared, resulting in relief of the premenstrual syndrome. These results support earlier hypotheses, suggesting that the premenstrual syndrome appears as a result of provoking factors produced by the corpus luteum. This view is in line with earlier therapeutic findings showing that induced anovulation can relieve the premenstrual syndrome. PMID- 1897331 TI - Effect of maternal thyroid autoantibodies and post-partum thyroiditis on the fetus and neonate. AB - Thirty-five pregnant women with thyroid antibodies were followed during pregnancy and 12 month post partum. Twenty antibody-negative women served as controls and none of these developed postpartum thyroiditis in contrast to 12 of 35 antibody positive women. Umbilical cord blood was collected at birth for measurements of thyroid antibodies, and blood samples for measurements of thyroid hormones were obtained at 5 and 30 days of age in the infants together with a clinical examination. There were no differences between the infants of antibody-positive and -negative mothers or the infants of those who developed postpartum thyroiditis with regard to gestational age at birth, birth weight, birth length or Apgar score, and no difference in thyroid function of the mothers and infants. However, serum TSH level was significantly higher in mothers who subsequently developed postpartum thyroiditis. Furthermore, a significantly lower growth during the first 30 days of life was observed in their infants. Our observations suggest a relationship between the maternal thyroid status in pregnancy and early growth in infancy. PMID- 1897332 TI - Size heterogeneity of circulating growth hormone in acromegaly. "Big-big" GH forms are associated with inappropriately low IGF-I levels. AB - Circulating GH consists of several molecular size species with different biological activity. A reduced sensitivity of some monoclonal antibodies towards high-molecular weight GH variants has been reported. The aim of the present work was to evaluate the molecular size species of circulating GH using Sephadex G-100 gel filtration chromatography in acromegalic patients and in normal subjects employing both RIA and an immunoradiometric assay for all GH determinations. In 6 normal subjects, studied under GHRH stimulation, little GH was 69.8 +/- 6% (mean +/- SD), big GH (44 kD) 26.4 +/- 6% and big-big GH (greater than 80 kD) 2.8 +/- 4%, in IRMA, with a good correspondence with RIA results (70.8 +/- 8, 27.0 +/- 4, and 3.2 +/- 2%, respectively). In 13 untreated acromegalic patients, studied in basal conditions, the little form constituted 76.2 +/- 7%, the big form 18.3 +/- 4%, which is significantly lower than in normals (p less than 0.05), and the big big form 5.5 +/- 7%. Similar results were obtained with RIA. A clear elevation of big-big GH (21% for both in IRMA, and 15.7 and 27.8% in RIA) was found in 2 patients with IGF-I levels lower than expected on the basis of mean GH concentrations. The study was extended to an additional acromegalic patient, previously operated and irradiated on, characterized by discrepant serum GH levels in RIA (4.6 micrograms/l), and in IRMA (1.4 micrograms/l), and by normal IGF-I levels. Serum GH showed a lack of parallelism to standard GH in RIA, but not in IRMA. RIA immunoreactivity was almost completely composed (92%) of a high molecular weight GH form (greater than 90 kD), not recognized by IRMA. All IRMA immunoreactivity eluted with a Kav corresponding to 19-50 kD. IN CONCLUSION: a. the three main molecular size isomers of serum GH are similarly recognized by IRMA and RIA methods in normal subjects. b. in acromegaly, both quantitative and qualitative modifications of the GH chromatographic profile may be present. In particular, increased amounts of big-big forms, whether or not recognized by monoclonal antibodies, have been observed. Their lower bioactivity, suggested by the normal or lower than expected IGF-I levels, can account for the discrepancy between serum GH levels and the clinical picture or IGF-I levels sometimes observed in acromegaly. PMID- 1897333 TI - Impaired conversion of cortisol to cortisone in chronic renal insufficiency--a cause of hypertension or an epiphenomenon? AB - To study the possible impairment of 11 beta-hydroxysteroid-dehydrogenase in patients with chronic renal insufficiency, urinary excretion rates of the four main glucocorticoid-metabolites, tetrahydrocortisol, tetrahydrocortisone, allotetrahydrocortisol and allotetrahydrocortisone were determined by capillary gas chromatography in 22 patients with chronic renal insufficiency with (N = 15) and without (N = 7) hypertension, but without hemodialysis treatment. Whereas the sum of all 41 steroid metabolites determined by capillary gas chromatography was reduced (p less than 0.001) in patients with chronic renal insufficiency as compared with 22 healthy individuals, the relative contribution of the four glucocorticoid metabolites to total steroid excretion was similar in patients with renal insufficiency (22 +/- 12%) and in healthy subjects (20 +/- 5%). However, the excreted amount of tetrahydrocortisol exceeded that of tetrahydrocortisone in all but 3 (normotensive) patients with chronic renal insufficiency, but only in one healthy subject resulting, in patients with chronic renal insufficiency, in a ratio of tetrahydrocortisone vs tetrahydrocortisone of 0.7 +/- 0.4 (hypertensive patients 0.5 +/- 0.2; normotensive patients 1.1 +/- 0.4; controls 1.9 +/- 0.9, p less than 0.001 vs patients with chronic renal insufficiency). This ratio of tetrahydrocortisone/tetrahydrocortisol showed a correlation with serum concentrations of creatinine (p less than 0.001). These results provide indirect proof of an impaired conversion of cortisol to cortisone in moderate renal insufficiency and may suggest a relationship with the hypertension frequently seen in this group of patients. PMID- 1897334 TI - Presence of CRH-binding protein in amniotic fluid and in umbilical cord plasma. AB - CRH-binding protein was present in the amniotic fluid and in the umbilical cord plasma after 15 weeks and 24 weeks of pregnancy, respectively. The size of the CRH-binding protein was similar to that in the peripheral blood from normal subjects. The level of the binding of CRH-binding protein in the umbilical cord plasma during the third trimester of pregnancy was also similar to that in the peripheral blood of neonates and normal adult subjects. The binding of CRH binding protein was temporarily decreased at 40 weeks of pregnancy. These results indicate that fetal CRH-binding protein seems to be produced at least in the second trimester of pregnancy. PMID- 1897335 TI - Endothelial cells stimulate proliferation of human thyroid epithelial cells. AB - The present study was undertaken to investigate cellular interactions between human thyroid epithelial cells (thyrocytes) and endothelial cells. Normal thyrocytes were cultured with either mitomycin C-treated endothelial cells or mitomycin C-treated human foreskin fibroblasts. The proliferative responses of thyrocytes were markedly stimulated by endothelial cells, but not by skin fibroblasts. The proliferative response of the thyrocytes obtained from patients with Graves' disease were similar to that of normal thyrocytes. Furthermore, the cell number of thyrocytes in endothelial cell-thyrocyte co-culture was markedly increased as compared with that in thyrocytes alone. The culture medium of endothelial cells only partly had any effect in the endothelial cell-thyrocyte co culture experiment. Indomethacin, a cyclooxygenase inhibitor, did not increase the endothelial cells-induced thyrocyte proliferation. Furthermore, the increased proliferative response of thyrocytes stimulated by endothelial cells was not suppressed by heparin. These results suggest that endothelial cells increase thyrocyte proliferation, and that cell contact or extracellular matrix production by endothelial cells may play an important role in the proliferation of thyrocytes. PMID- 1897336 TI - The influence of growth hormone and thyroxine on iodothyronine deiodinase activity in the liver, kidney and brown adipose tissue in hypophysectomized rats. AB - The effects of GH and T4 substitution on peripheral iodothyronine deiodinase activity in the liver, kidney and brown adipose tissue of hypophysectomized rats were investigated. Animals were treated with GH (140 micrograms hGH/day), T4 (3 micrograms/day), GH plus T4 (same doses), or saline. Rats were killed 0, 4, 7 or 11 days after treatment was started. Non-hypophysectomized, age-matched rats were killed after 0 and 11 days and served as controls. GH plus T4 restored body weight gain to normal, whereas GH alone and T4 alone did not. Tissue deiodinase activity and T3 concentrations were severely depressed in the hypophysectomized rats compared with non-hypophysectomized controls (to less than 10%). GH substitution in hypophysectomized rats led to a slight but significant elevation in tissue iodothyronine deiodinase activity in the liver and kidney, without concomitant increases in T3. Deiodinase activity in brown adipose tissue did not differ from that in saline-treated controls. T4 administration normalized deiodinase activity and tissue T3 content in all the evaluated tissues. GH plus T4 resulted in a lesser increase in deiodinase activity than T4 alone in the liver and kidney (p less than 0.01 at day 11), whereas no significant difference was observed in brown adipose tissue. In conclusion, GH stimulates iodothyronine deiodinase activity of the liver and kidney in hypophysectomized rats. Moreover, when GH is administered together with T4, the T4-stimulated enzyme activity in the liver and kidney is downregulated, suggesting that GH attenuates (or modulates) the T4 effect on this specific enzyme activity. PMID- 1897338 TI - The test dose in regional anaesthesia. PMID- 1897337 TI - Chronic hypernatremia due to impaired osmoregulated thirst and vasopressin secretion. AB - We report the case of a young man who became adipsic following a subarachnoid hemorrhage and subsequently had two episodes of life-threatening hypernatremia. Investigations demonstrated that he had defective osmoregulated thirst and AVP release, but normal AVP responses to hypotension and nausea. There is also evidence that he had intact baroregulated thirst. We discuss the results of our investigations in the context of current models of hypothalamic-neurohypophysial function. PMID- 1897339 TI - Postischaemic renal cortical microcirculation and tissue oxygenation in the pig. AB - Porcine and human renal physiology are similar in important aspects. Renal cortical microcirculation and its relation to inulin clearance (CIn) was therefore studied before and after renal ischaemia in 28 pigs under continuous intravenous chlormethiazole-pancuronium anaesthesia. The anaesthesia used provided essential stability in central haemodynamics. The animals were studied for 90 min of reperfusion following 0, 30 or 60 min of renal ischaemia. Twelve of the animals (four were subjected to each duration of ischemia) were also studied 18 h after start of reperfusion. Regional blood flow in the superficial renal cortex was measured by laser Doppler flowmetry (LDF), and tissue oxygenation (PtO2) by surface microelectrode technique. These techniques allow continuous or repeated measurements. During the first 90 min of reperfusion, superficial renal cortical blood flow measured by LDF (Qsrc) underwent considerable temporal variation which followed a certain pattern. Thus, when the renal arterial blood flow was restored after ischaemia, we observed an instant peak in Qsrc followed by a decreasing flow until a minimum value (Qmin) was reached between 3 and 9 min after start of reperfusion (tQmin). Thereafter, Qsrc increased until a maximal value (Qmax) was reached between 11 and 64 min after start of reperfusion (tQmax). The parameters tQmin and tQmax were related to inulin clearance 18 h after start of reperfusion (P less than 0.05 and P less than 0.01, respectively). Thus, it might be possible soon after start of reperfusion--to evaluate the severity of ischaemic damage. This could be useful in the evaluation of different prophylactic strategies, since the full extent of the ischaemic damage, as assessed by clearance determinations, cannot be established until hours later.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1897340 TI - Postischaemic regional microvascular variations in the porcine renal cortex. AB - Regional microcirculatory differences in the superficial renal cortex were studied before and during 4 h following 60 min of renal ischaemia in seven pigs under continuous intravenous chlormethiazole-pancuronium anaesthesia. Superficial renal cortical blood flow (Qsrc) was measured by laser Doppler flowmetry (LDF) in two different regions. In two other different regions tissue oxygenation (PtO2) was measured by surface electrodes. Thus, microcirculatory measurements were simultaneously carried out in each animal in four different regions of the left kidney. After 60 min of renal ischaemia, pronounced renal cortical microcirculatory disturbances were found. The regional microcirculatory differences were notable, especially after ischaemia. On average, Qsrc was 49 +/- 11 (s.d.) arbitrary units at baseline and decreased to 24 +/- 4 arb. units 4 h after start of reperfusion (P less than 0.05). Before ischaemia the average difference between Qsrc simultaneously measured in two different parts of the renal cortex was 26 +/- 15% of the mean of both measurements, and it was 30 +/- 22% 4 h after start of reperfusion (n.s.). Mean PtO2 (m-PtO2) was on average 4.5 +/- 1.3 kPa at baseline and 2.4 +/- 1.5 kPa 4 h after start of reperfusion (P less than 0.05). The average difference between m-PtO2 simultaneously measured in two different parts of the renal cortex at baseline was 24 +/- 13% of the mean of both measurements and 57 +/- 49% 4 h after start of reperfusion (n.s.). In each of the two measured regions of the renal cortex m-PtO2 was calculated from 160 small tissue volumes distributed within a surface area of about 1 mm2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1897341 TI - Comparison of North American and European malignant hyperthermia group halothane contracture testing protocols in swine. AB - Different in vitro halothane testing procedures have been used in the European malignant hyperthermia (MH) Group Protocol (EMHGP) and the North American MH Group Protocol (NAMHGP), whereas the caffeine-testing protocols are very similar. The present study compares the two halothane-testing protocols in ten MH susceptible swine and in four control swine. Halothane contracture testing was conducted in vitro 12-52 days following the barnyard challenge that established the MH susceptibility of the swine. There was one false positive and one false negative halothane test by the EMHGP. The MH-equivocal category in the EMHGP, which is treated clinically as MH-susceptible, affords a margin of safety in such cases. In contrast, there were no false halothane tests by the NAMHGP. While some skeletal muscle strips from MH pigs were normal by both protocols (NAMHGP 30%; EMHGP 10%), the outcome of halothane testing by the NAMHGP was unaffected. The response to halothane 3% is reduced if preceded by the EMHGP, suggesting that simply adding halothane 3% to the end of the EMHGP does not permit a direct quantitative comparison to the NAMHGP. However, the diagnostic outcomes of the two approaches are similar. PMID- 1897342 TI - Effects of bupivacaine and calcium antagonists on human uterine arteries in pregnant and non-pregnant women. AB - Bupivacaine is a local anesthetic commonly used in obstetrical practice. Although not generally constrictive, it has a constricting effect on blood vessels in clinically used doses, and when administered close to the uterine vasculature, as in a paracervical blockade, it can induce severe fetal bradycardia and thus be hazardous to the fetus. The bupivacaine-induced vasoconstriction on uterine arteries from pregnant and non-pregnant women was effectively reduced by two different calcium antagonists, verapamil and nifedipine. In non-pregnant women, nifedipine (2.9 x 10(-7) mol.l-1) administered simultaneously with bupivacaine (5.8 x 10(-4) mol.l-1) caused a 96% and verapamil (10(-5) mol.l-1) an 84% reduction as compared with the control vessel where only bupivacaine (5.8 x 10( 4) mol.l-1) was administered. In pregnant women, nifedipine 2.9 x 10(-7) mol.l-1 and 2.9 x 10(-6) mol.l-1 produced 66% and 79% reductions, respectively. It is possible that calcium antagonists administered together with bupivacaine in paracervical blockade could reduce the risk of fetal bradycardia. PMID- 1897343 TI - Individual predictability of repeated spinal anaesthesia with plain 0.5% bupivacaine. AB - To evaluate the individual predictability of spinal anaesthesia, 10 patients (3 women and 7 men) scheduled for control cystoscopy were studied twice within 9 months. Lumbar puncture was performed in the midline at the L2/3 interspace with the patient in the sitting position using plain 0.5% bupivacaine at 37 degrees C. A non-parametric Spearman test showed that, on the basis of the first block, the predictability of the cephalad analgesic spread of the second anaesthesia was high up to 60 min after injection. Thereafter the predictability decreased. The predictability of the motor blockade was generally low. Six patients obtained complete motor blockade twice; the remaining four, once. PMID- 1897344 TI - Plasma renin, catecholamines, vasopressin and aldosterone during hypotension induced by labetalol with isoflurane. AB - Deliberate hypotension may induce secretion of stress hormones. In the present study, the effects of hypotension induced by labetalol with isoflurane or plasma renin activity, plasma concentrations of adrenaline, noradrenaline, vasopressin, and aldosterone were investigated in eight adult patients undergoing middle-ear surgery. The mean arterial pressure was 50 mmHg (6.7 kPa) during hypotension. Plasma renin activity rose significantly during anaesthesia before hypotension, being similar during hypotension and before hypotension, and in returned postoperatively to the initial level. Plasma adrenaline fell significantly during hypotension and rose after anaesthesia to the preanaesthetic level. Plasma noradrenaline rose slightly during hypotension and after anaesthesia, but not significantly. Plasma vasopressin rose significantly after anaesthesia. Plasma aldosterone increased slightly throughout the study, but not significantly during any phase. In conclusion, labetalol with isoflurane-induced hypotension seems to attenuate the stress response in these operations. During hypotension, plasma renin activity is not an essential compensatory mechanism, which antagonises the decrease of blood pressure. Plasma vasopressin has no role in regulating blood pressure during labetalol-induced hypotension. PMID- 1897345 TI - Pretreatment with pancuronium before suxamethonium administration in patients heterozygous for the usual and the atypical plasma cholinesterase gene. AB - The object of this study was to investigate whether pretreatment with pancuronium before i.v. injection of suxamethonium could cause prolonged neuromuscular blockade in patients heterozygous for the usual and the atypical plasma cholinesterase gene (E1uE1a). Forty-three patients, 23 with genotype E1uE1a and 20 with normal genotype (E1uE1u), were pretreated with pancuronium 0.01 mg.kg-1 followed by suxamethonium 1.5 mg.kg-1, and received either neurolept anaesthesia or halothane anaesthesia. Seven patients (E1uE1a) were given suxamethonium 1.5 mg.kg-1 without pretreatment. The duration and type of neuromuscular block were evaluated using train-of-four (TOF) nerve stimulation. Type of anaesthesia did not significantly influence the results. The duration of block following pretreatment was significantly longer in heterozygous patients than in normal patients. Time to 90% twitch height recovery was 10.7 +/- 1.2 min (mean +/- s.d.) in genotypically normal patients, and 18.0 +/- 4.2 min in patients with genotype E1uE1a. Pretreatment with pancuronium caused a significantly slower recovery of the TOF ratio (phase II block). Thus, a TOF ratio of 0.7 was always reached within 13 min in genotypically normal patients. In genotypically abnormal patients, the same TOF ratio was reached within 20 min in all but three patients. In these three patients time to 90% twitch height recovery was prolonged (18-31 min), and TOF ratio did not return to normal, but stabilized at about 0.35, 0.50, and 0.65, respectively. Injection of edrophonium restored normal neuromuscular function in 10 min. It is concluded that in patients heterozygous for the usual and the atypical gene, pretreatment with pancuronium in combination with an increased dose of suxamethonium may cause a phase II block and thus a prolonged neuromuscular block. PMID- 1897346 TI - Effects of thoracic epidural anesthesia on myocardial pH and metabolism during ischemia. AB - The effect of thoracic epidural anesthesia (TEA) on the ischemic myocardium was examined in open-chest dogs anesthetized intravenously. Ischemia induced by brief coronary artery occlusion caused an elevation of the ST segment in epicardial ECG and a reduction in myocardial pH and contractile force. TEA with 0.15 ml/kg of 0.4% bupivacaine solution attenuated an ischemia-induced decrease in myocardial pH and an increase of the ST segment in epicardial ECG. This attenuation was maintained even after the restoration of blood pressure and heart rate, which had been decreased significantly after TEA, to pre-TEA levels, suggesting that a beneficial effect of TEA should not be confined to its hemodynamic changes such as decreased blood pressure and heart rate. In contrast, the subendocardial contents of ATP, creatine phosphate (CP) and lactate were not affected by TEA, either in the presence or the absence of 5 min LAD occlusion. These results suggest that neither hemodynamic nor metabolic changes are responsible for the reduced myocardial ischemic acidosis induced by TEA after brief coronary artery occlusion. The acidosis-saving property of TEA is favorable for the ischemic heart. PMID- 1897347 TI - Continuous epidural infusion of bupivacaine and morphine for postoperative analgesia after hysterectomy. AB - The analgesic efficacy and side-effects of combined epidural infusion of bupivacaine and morphine, in comparison with these drugs alone, for postoperative analgesia after hysterectomy (60 patients) were evaluated. Before general anaesthesia, all patients had an epidural catheter placed (Th11-12) and 20 ml of 0.5%, bupivacaine was injected. In random order, epidural infusion was continued for 24 h with either 0.25% bupivacaine 4 ml.h-1 (BUPI-group), a bolus of 2 mg of morphine followed by morphine 0.2 mg.h-1 (MO-group), or a combination of the two drugs (COMB-group). A urinary bladder catheter was kept for 24 h. Supplementary postoperative pain medications were i.m. morphine 0.1 mg.kg-1 or rectal indomethacin 50 mg, on request. Immediately after awakening from general anaesthesia and transfer to the recovery room, 18/20 of the BUPI-group patients, 17/20 of the MO-group patients and 19/20 of the COMB-group patients were pain free. In the postoperative evening and the first postoperative morning, the corresponding figures were 7/20 and 10/20 in the BUPI-group, 15/20 and 15/20 in the MO-group, and 18/20 and 15/20 in the COMB-group (postop, evening; P less than 0.01 BUPI vs. others). The number of patients requiring supplementary analgesics (morphine and indomethacin during the first 24 h was greatest in the BUPI-group P less than 0.01). The number of patients who vomited during the 24-h period was 3 in the BUPI-group, 9 in the MO-group and 5 in the COMB-group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1897348 TI - Local vascular effects of isoflurane during regional intestinal hypothermia in cats. AB - The influence of isoflurane on intestinal blood flow (IBF) during regional intestinal hypothermia (28 degrees C intraluminal temperature) was investigated in cats (n = 12) during basal chloralose-nitrous oxide anesthesia. A jejunal segment, which was dissected free in situ and intermittently cooled in a saline bath, was perfused via an extracorporeal arterial circuit which included a roller pump and a variable arterio-venous shunt. Intestinal perfusion pressures were controlled by adjusting the shunt flow. IBF was measured (optical drop-recording) during regional normothermia and hypothermia. The protocol included steady-state recordings at defined perfusion pressures (50, 75, 100, 125 and 150 mmHg in a randomized order; 6.7, 10.0, 13.3, 16.7 and 20.0 kPa, respectively) with and without the addition of 0.7% isoflurane. During normothermia, IBF levels were higher during isoflurane anesthesia than during basal chloralose anesthesia. Regional intestinal hypothermia induced no significant changes in IBF during basal chloralose anesthesia. However, the intestinal vasodilator effects of isoflurane, as shown during normothermia, were efficiently countered by regional cooling of the intestinal segment to 28 degrees C. Accordingly, hypothermia IBF levels were similar, regardless of whether isoflurane was administered or not. This could have an impact on the choice of anesthetic techniques. PMID- 1897349 TI - Clinical evaluation of electrostimulation anaesthesia for hysterectomy. AB - A prospective randomized study was undertaken to evaluate the efficacy of electrostimulation anaesthesia (ESA) when compared with neurolept anaesthesia (NLA). One hundred patients scheduled for hysterectomy received either ESA or NLA. Higher levels of mean arterial pressure and heart rate in the ESA group make this technique less suitable for patients with a history of arterial hypertension. A higher dose of muscle relaxants was used in the ESA group. Measured stress variables like plasma glucose, cortisol, and iron indicate maintenance of the stress response during ESA. The postoperative questionnaire revealed intraoperative recall in 12% of ESA patients. We conclude that "pure" ESA based on a N2O regimen should be avoided. PMID- 1897350 TI - The efficacy of intravenous indomethacin in prevention of postoperative pain. AB - Since intravenous prophylactic anti-inflammatory agents have been suggested to reduce or even replace opiates in postoperative pain therapy, we studied the demand for morphine in 45 patients recovering from abdominal surgery who had received a baseline infusion of either indomethacin, morphine or saline placebo. When extubated after inhalational anaesthesia, each patient received an i.v. bolus of either 0.5 mg.kg-1 indomethacin, 0.07 mg.kg-1 morphine or saline placebo. Thereafter a 20-h infusion of the same test analgesic was started, either 0.1 mg.kg-1.h-1 indomethacin, 0.03 mg.kg-1.h-1 morphine or saline placebo. For additional analgesia, a patient-controlled analgesia device (PCA) delivering 5-mg boluses of morphine was used. For the first 5 postoperative hours, significantly more (P less than 0.05) PCA morphine was needed in the indomethacin group (35 mg) than in the morphine group (24 mg), while the placebo group demanded mean 30 mg. For equal analgesia (measured by VAS and VRS) between 5-20 h, similar amounts (mean 23 and 19 mg) of PCA morphine were required in the indomethacin and morphine groups, in contrast to the placebo group (mean 40 mg) (P less than 0.001). Morphine infusion increased the total consumption of morphine by 25% as compared to placebo. We conclude that, following abdominal surgery, the analgesic effect of indomethacin infusion became apparent after the first 5 postoperative hours, thereafter reducing the demand for PCA morphine by about 40%. Continuous morphine infusion diminishes the postoperative demand for PCA morphine, but also increases the total morphine consumption. PMID- 1897351 TI - The caffeine contracture test for malignant hyperthermia: caffeine citrate, caffeine benzoate or caffeine free base? AB - The aim of the present study was to investigate whether the three different caffeine preparations--caffeine citrate, caffeine benzoate and the free base- used for in vitro diagnosis of malignant hyperthermia susceptibility--produced the same amount of contracture in rat diaphragm. At equimolar caffeine concentrations, the pure base generated more tension in the rat diaphragm muscle than caffeine benzoate or caffeine citrate. The citrate lowers the pH and the free Ca2+ concentration of the test bath and thus suppresses the caffeine contracture. The benzoate is believed to inhibit the caffeine contracture by its carbonyl group in a way similar to the effect of benzocaine. PMID- 1897352 TI - Action of propofol on resistance and capacitance vessels during cardiopulmonary bypass. AB - The peripheral vascular action of propofol on the resistance and the capacitance vessels was investigated in 16 patients during cardiopulmonary bypass. The venous reservoir (RV) and mean arterial pressure (MAP) were used as indices of the changes in venous capacitance and systemic vascular resistance (SVR), respectively. Propofol 2 mg.kg-1 produced a decrease in MAP without a significant change in RV, suggesting that propofol preferentially decreases SVR without a significant change in venous capacitance. PMID- 1897353 TI - Changes in body heat during hip fracture surgery: a comparison of spinal analgesia and general anaesthesia. AB - Postoperative hypothermia initiates an increased oxygen demand in the postoperative period and may endanger patients with restricted cardiopulmonary reserves. In order to compare net heat losses and gains, we studied 28 women undergoing hip fracture surgery, using either general anaesthesia or spinal analgesia. The superficial and central temperatures were followed in the per- and postoperative period. Total body heat was calculated from temperature measurements. Temperature changes were unrelated to the type of anaesthesia. Large net heat losses occurred on transfer to the recovery room. PMID- 1897354 TI - Early detection of hearing impairment: what role is there for behavioural methods in the neonatal period? AB - A survey of the use of behavioural methods for neonatal hearing screening in 1985 (1) concluded that the future for automated methods was quite promising. Since then several studies have assessed the two main automated behavioural tests: the Auditory Response Cradle (ARC) and the Crib-o-Gram (COG). As a screen targeted at neonatal intensive care unit (NICU) babies and other high risk groups (at present the most cost-effective form of neonatal hearing screening), the ARC is shown to have low sensitivity, even for severe hearing impairments, and the COG has an unacceptably low specificity. Any future for behavioural testing during this period must therefore rely on new implementations flowing out of a fundamental understanding of (a) the way in which neonates respond to sound and (b) the ways in which a behavioural test might complement screening with Auditory Brainstem Responses (ABR) or Evoked Oto-acoustic Emissions (EOAE). A clearer understanding of the relative benefits of detecting different degrees of hearing impairment at birth in both the NICU population and the unrestricted population is urgently needed. To determine what role should be played by specific screening programmes such benefits need to be balanced against the total costs of screening assessment and rehabilitation, in which false positives (low specificity) play a large part. PMID- 1897355 TI - Detection of the infant with congenital/early acquired hearing disability. AB - The age at identification and intervention in different samples of children with congenital/early acquired hearing disability is described. The prevalence of congenital/early acquired hearing disability was 1.3/1,000. Among hearing disabled children born 1970-1975 only 16% were identified at the age of one year, whereas among children born 1980-1985, 37% were identified at this age. Children at-risk are not identified earlier than children not-at-risk. In 50-60% the parents are the first to suspect their child's hearing disability, and it is emphasized that non-professional screening resources are present in the general population and should be taken into account. Better information to both professionals and non-professionals about high-risk criteria and about the signs of hearing disability in combination with easy access to a professional audiological unit could improve the early detection and intervention of hearing disabled children. PMID- 1897356 TI - Behavioural tests: applications and limitations in comparison with brainstem response audiometry. AB - Conditioned behavioural hearing tests cannot be performed in children before the developmental age of 8 months. Informal tests cannot be used as threshold tests as the stimuli are unspecific in frequency, and the observed reactions are not equivalent to the threshold level. Brainstem response audiometry (BRA) was performed on 47 children (23 normal children and 24 children with mental retardation with or without behavioural disturbances) in whom informal test results were unclear. The BRA was followed up by behavioural tests 1 to 10 years later. In none of the cases did the BRA thresholds indicate better hearing function than the actual threshold noted later on at behavioural tests. High BRA thresholds (up to 75 dB nHL) were found in 5 normal-hearing children with serous otitis media at the time of BRA recording. PMID- 1897357 TI - Effectiveness and efficacy of early detection of hearing impairment in children. AB - Throughout the industrial world, technology and techniques are now available so that any child, no matter how young or how impaired, can have an accurate and precise assessment of middle ear function, auditory reactivity, and physiological processing of auditory stimuli. Yet, a major problem exists in the lack of timely identification of many children with hearing impairments. Presently, identification systems are primarily proactive and are based on technology. These consist of testing of infants with biological risk factors and the use of hearing screening programs at various times during the first decade of life. The reactive sources of referral appear to be inadequate, an impression that is supported by the data on the delay of diagnosis. These inadequacies appear to be due to a lack of awareness on the part of health providers as to the potential hearing losses; ignorance concerning the ability to diagnose them; and a lack of awareness of the potential of effective intervention. Two additional approaches are suggested which would be added to those already existing for improving the number of children who will have their diagnoses made in a timely fashion. The first of these is educational: health providers should have required and continuing education concerning the effects of hearing loss, the ability to diagnose, and to intervene effectively. A parallel educational program should be provided for the public. The second is the periodic assessment of speech and language from early infancy through the first few years of life for all children. This would enable children with suspected impairments to be referred for definitive testing.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1897358 TI - Electrocochleography: applications and limitations in young children. AB - Electrophysiological measurements of auditory function are especially indicated in children who are difficult to test by behavioral audiometry. This report is concerned with transtympanic electrocochleography (ECochG) findings in young children (0-3 years) who were examined over the last 6 years in order to extend behavioral audiometric data. On an average, 25% of the children tested with auditory brainstem responses (ABR) needed general anesthesia and were therefore also investigated with ECochG (n = 65). These ECochG children often showed developmental retardation, and behavioral audiometry was doubtful or not possible in 60% of them. ECochG thresholds were generally similar on both ears. Despite general agreement between thresholds obtained by ECochG and behavioral audiometry, differences were found in both directions, ECochG being better or worse than hearing in several children. Detection of severe threshold elevation and low frequency residual hearing remain major limitations of ECochG in the early diagnosis and rehabilitation of deafness in young children. PMID- 1897359 TI - Evaluation of electrocochleographic audiogram determination in infants. AB - An evaluation was made of results of electrocochleography (ECoG) in a group of 75 children, tested during the last four years in the ENT department of the Leiden University Hospital. Eleven years was taken as the upper age limit; 79% of our group were younger than three and a half years. In only 60% of the children the cause of the hearing loss was clarified. In this group maternal rubella followed by meningitis and retardation were the most frequent cases of deafness. Cochlear microphonics (CM) could be measured in all the children. Examples are given of cochlear responses of children belonging to 6 different threshold categories. The responses of the largest category (56 children) with the highest loss (larger than 80 dB) were very abnormal. For the categories with less hearing loss the ECoG was not restricted to threshold determination and the origin of the hearing loss could be demonstrated, while a contribution of conduction loss could be derived from a horizontal shift of the latency-intensity function to higher intensity levels. The potentialities and limitations of ECoG and brainstem electric response audiometry (BERA) for threshold determination are discussed, particularly against the background of the time consumption of both procedures and the invasive character of ECoG. PMID- 1897360 TI - Electric response audiometry in infants and preschool children. Long-term control of the results. AB - Two hundred and four infants and preschool children (mean age 2 years and 7 months +/- 9 months) with auditory impairment according to ABR and ECochG data, and 33 subjected to SVR were followed up for periods ranging from 1 year to 4 years and 6 months until a reliable conventional pure tone audiogram was obtained. One hundred and fifty-one children had conductive hearing loss, 75 sensorineural, 7 had ABR indicating disorders of the central auditory pathways, 5 were normal. Hit, false positive and false negative rates resulted as follows: 58.62%, 17.24% and 24.14% for SVR: 98.37%, 1.63% and 0% for ABR; 99.15%, 0.85% and 0% for ECochG. In the group with sensorineural hearing loss, 75% of the children gave ECochG detectable responses at 90 dB nHL, against 51.5% with ABR. With 1 kHz tonebursts, 64% of the tested subjects gave threshold responses to ECochG and 12% to ABR. The best strategy for children who failed the behavioral hearing tests, or in whom these tests were not applicable, was that based on ABR and middle ear impedance measures, complemented, when necessary, by ECochG. PMID- 1897361 TI - A timesaving BERA technique for frequency-specific assessment of the auditory threshold through tone-pulse series stimulation (TOPSTIM) with simultaneous gliding high-pass noise masking (GHINOMA). AB - A new stimulation paradigm is described for eliciting frequency-specific auditory brainstem responses (ABR) by stimulation with a series of seven Gaussian-shaped tone pulses with carrier frequencies descending, in half-octave steps, from 4,000 to 500 Hz, and an interstimulus interval between consecutive pulses of 18 ms. The pause between two consecutive series is 54 ms so that the interval between two tone pulses of the same frequency is 162 ms (stimulus repetition rate approximately 6/s). Simultaneously a high-pass noise masker is presented whose lower cut-off frequency is continuously diminished in such a way that, when a tone pulse is presented, the cut-off frequency of the masker is exactly one octave above the carrier frequency of the pulse. Forward masking effects of preceding tone pulses as well as forward and simultaneous masking effects of the high-pass noise suppress activity originating from those regions of the cochlea which are located basalwards to the region to be stimulated by the respective pulse, thus enhancing the frequency specificity, especially for low-frequency stimuli of higher intensity. The new stimulation paradigm was tested in 12 normal hearing subjects and turned out to be suitable to elicit frequency-specific ABR with frequencies as low as 500 Hz and intensities as low as 10 dB nHL. The main advantage of the described technique is that the time required for a complete assessment of the auditory threshold at seven test frequencies (covering the relevant speech frequency range) is substantially shorter as compared to conventional techniques so that it can routinely be employed in pedaudiology, where infants usually have to be investigated in sedation. PMID- 1897362 TI - Low frequency hearing threshold determination in newborns, infants and mentally retarded children by middle latency responses. AB - Middle latency (10-50 ms) responses (MLR) evoked by tone-pips (1,000 Hz 500 Hz) and early (0-10 ms) auditory evoked potentials (EAEP) evoked by chicks were recorded on 68 newborn babies (premature or at term), infants and children, some with central nervous system or psychiatric disorders, who had normal or impaired hearing. MLR were obtained either during sleep, chloral-hydrate sedation or ketamine anesthesia. Thresholds estimated from MLR and EAEP were compared to those from subsequent psychoacoustic pure tone testing. We confirm that MLR provide good threshold estimates for hearing in the low frequency range, whereas click evoked EAEP are good threshold indicators only for high frequencies. PMID- 1897363 TI - Development of the human cochlea. AB - This paper summarizes the most recent findings dealing with the anatomical development of the human cochlea, and especially with ultrastructural data from both scanning and transmission electron microscopic studies. It also briefly reviews physiological findings and attempts to specify the timing of the main developmental events, i.e. the onset of function, the acquisition of adult properties, and the sensitive periods. PMID- 1897364 TI - Early detection of hearing impairment in children. Proceedings of a workshop. Montpellier, France, 21-22 November 1988. PMID- 1897366 TI - Evoked otoacoustic emissions from normal newborns and babies admitted to an intensive care baby unit. AB - Click-evoked otoacoustic emissions (OAEs) were recorded from both ears in two groups of neonates ranging in age from a few days to two months after birth. The first group consisted of 55 full-term neonates with normal developmental history and health status, including absence of middle ear disease and familial history of hearing loss. The second group consisted of 40 infants admitted to an intensive care baby unit for various pathological conditions (anoxia, prematurity, hyperbilirubinemia, meningitis). The method achieved 97% success in assessing cochlear function in the normal group; it was possible to identify a clear and reproducible response in all ears, except 3, at 70 dB SPL (i.e. approximately 30 dB nHL). The detection-threshold of OAEs was comparable to that measured in adult ears. Several babies from the second group produced no OAEs and were also tested by auditory brainstem responses (ABR): these infants demonstrated ABR thresholds higher than 30 dB nHL. OAEs provide an objective tool for a rapid and effective screening test for cochlear impairment in neonates. PMID- 1897365 TI - Otoacoustic emission tests in neonatal screening programmes. AB - Otoacoustic emission (OAE) testing has many characteristics which suit it for use as an objective neonatal auditory screener. The most important of these is the speed with which it can be performed. This feature alone opens up the possibility of much more general neonatal screening programmes. We here review the important considerations in applying otoacoustic testing to neonatal screening applications, and discuss the future role of OAE testing. Practical considerations in applying the technique are illustrated by examples and experiences drawn from a pilot whole-population neonatal screening project. Unselected screening takes us into unexplored territory. Test failure rate will inevitably far exceed the real incidence of hearing impairment. The concept of rapid whole-population neonatal OAE screening techniques as an additional risk factor detector rather than a definitive hearing test seems more appropriate to the low incidence of hearing impairment in the population and to the ethical problems surrounding early and erroneous diagnosis of hearing impairment. PMID- 1897367 TI - Validity of large scale standardised behavioural screening. AB - A nation-wide screening programme in the Netherlands is described. 86% of all children are invited at the age of 9 months for the three-stage Ewing screening: 94% participate. The screening procedure is standardized in very great detail, including test, registration, training and guidance. The objective of the screening programme is to detect moderate to severe sensorineural hearing loss as well as long-standing conductive hearing loss. Tympanometry studies clearly show that the selection process of conductive hearing loss is associated with otitis media with effusion (OME) lasting 3 months or more. Studies on two cohorts of children with sensorineural hearing loss show test standardization and training to be vital elements of behavioural screening. All studies show validity parameters of 85% or more. PMID- 1897368 TI - [Use of CO2 laser in conservative surgery of glottic tumors]. AB - The present work evaluates the results obtained in a group of 360 patients with laryngeal-glottic tumors (classification T1/T2-N0-M0) who, in the last 10 years, have undergone direct microlaryngoscopy surgery employing a CO2 Laser. In the T1 glottic carcinomas the neoplasm was limited to the vocal cord on one side or it involved the anterior commissure and, most likely, the vocal cord on the opposite side; in T2 glottic tumors the extension reached the hypoglottic region and/or the Morgagni ventricle and the false vocal cords on one or both sides but without compromising laryngeal motility. The five year healing rate for the T1 tumors proved to be 84.7% while it was 74% for the T2 forms. In 36 cases complications were found which can be broken down as follows: - limited local recurrences (13 patients) requiring subsequent direct microlaryngoscopy; - regional lymph node metastases (6 patients) without reproduction of the primary neoplasm; in general (5 of the 6 cases) these patients underwent lateral neck dissection; - spreading of the neoplastic process (17 cases) which made total laryngectomy with lateral neck dissection necessary; this procedure was performed in 15 cases. When these subsequent surgical procedures are also taken into account the percentage healing rises to 94.3% for T1 glottic tumors and to 84.9% for T2. Detailed analysis of the case study, comparison with the data found in the relative literature regarding patients treated with traditional techniques, a series of observations on the advantages and disadvantages inherent to the techniques employed have all led to the conclusion that the use of a CO2 laser in the treatment of laryngeal tumors gives excellent results in terms of prognosis. Moreover, this technique offers significant advantages over the traditional methods and constitutes a reliable technique for partial laryngectomies as long as the indications are accurately applied and the proper techniques used. PMID- 1897369 TI - [Determination of 11S IgA in nasal secretions in the monitoring of local immunomodulating therapy]. AB - Twenty pediatric patients with recurrent infectious diseases of the upper respiratory tract (tonsillitis, adenotonsillitis with or without involvement of the ear and/or lower respiratory tract) were studied. An immunological assay of the nasal secretum was performed at time of diagnosis and following treatment with a local immunomodulator drug, administered by spray. The 7S, 11S IgA and albumin rates were evaluated. The authors emphasize the importance of SIgA in mucose defense mechanisms as well as the need for a selective method for determining the 11S IgA level. An original method for immuno-isoelectrofocusing (IIEF) determination was employed in the present study. After treatment a significant increase in 11S IgA level was observed, especially in those patients with a significant basal SIGA deficit. The authors describe details of the technique for determination and discuss the results. PMID- 1897370 TI - [Our experience in microsurgery of rhino-sinus phlogosis]. AB - Rhino-microscopy has made great progress in the diagnosis and surgical treatment of rhino-sinus phlogosis. In fact, a larger portion of the endonasal pathologies, which would not otherwise have been detected, can now be diagnosed through rhino microscopic exploration. From the surgical point of view microscopy offers a clear, enlarged operating field. Moreover, with the aid of an autostatic speculum, it frees the surgeon to use both hands. These features make intricate, precise surgery possible thus enabling preservation of those structures which are not involved in the disease. At the same time it allows for re-establishment of the physiological functionality of the rhino-sinus cavity. Between 1980 and 1989 the microsurgery technique was employed in 950 cases of rhino-sinus cavity surgery. The results achieved using this technique were quite good and the number of complications was quite limited although the number of patients to be followed up over the years was not sufficient to draw any statistical conclusions. For several years now optic-fibre endoscopy has also been employed. This, too, is a functional technique although the method and instruments are totally different. It is not the intention of the authors here to assert that microsurgery is superior to endoscopy even though some technical details (i.e. the ability to operate with both hands) has made it easier to use, particularly for those accustomed to using a microscope. It is, however, felt that for rhino-surgery it is advisable to be familiar with both techniques so that they can be used alternately depending on the type of pathology and patient. PMID- 1897371 TI - [Immunohistochemical study of monomorphic adenoma (clear cell and basal cell) and pleomorphic adenoma of the parotid gland]. AB - The present paper reports the results of an immunohistochemical study of 6 cases of monomorphic (2 clear cell, 4 basal cell) and 12 cases of pleomorphic adenomas in the parotid gland. The surgical specimens, embedded in paraffin, were tested by antisera vs. epithelial cell markers with epithelial membrane antigen (EMA) and cytokeratins (CK). They were also tested vs. myoepithelial and non-epithelial markers with S-100 protein and Glial Fibrillary Acidic Protein (GFAP). In pleomorphic adenomas, positive cells were found for all the tested antigens. Positive cell distribution showed a marked variability from case to case and even within each area, depending on cell morphology. In particular, areas showing tubular structures were constantly EMA-positive and CK-positive in more than 50% of the cases. In epithelioid areas EMA was negative while many cells were variably positive for CK, S-100 and GFAP. At times, the same cell proved positive to two different antigens. In those fuso-stellate (myxoid) cell areas considered to be of myoepithelial origin, cells were slightly CK-positive and widely GFAP and S-100 positive. In basal cell adenomas, widespread CK positivity was uniformly present while rare, focal positivity was evidenced for EMA and widespread non reactivity was found for S-100 and GFAP. In clear cell adenomas focal CK expression was found in the tubular lumina while clear cells, of myoepithelial origin, were steadily S-100 positive and GFAP-negative. It was noted that a sort of S-100/GFAP positive myoepithelial cell with fuso-stellate morphology was present in pleomorphic adenomas.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1897372 TI - [New knowledge on endo-oral submandibular sialoadenectomy]. AB - The present work reports personal modifications to the classical endo-oral surgical technique used to remove the submaxillary gland (Bourguet and Branchu surgery). The top of the tongue is transfixed with a silk thread and drawn out of the mouth laterally. An incision from the outlet of the Wharton duct to the base of the anterior palatine arch makes possible a full view of the sublingual extension of the submaxillary gland and the point where the lingual nerve crosses the Wharton duct. The sublingual gland may be removed to broaden access to the muscular hiatus of the mylohyoideus and hyoglossus muscles. The edges of the submaxillary gland are then identified and dissected from the muscle plane. At this point the sublingual extension of the submaxillary gland is detached from the lingual nerve which is medialized and shifted backward. The branches of the submental artery feeding the gland are isolated and pinched off so that the submaxillary gland can be removed from behind its anterior pole. Draining forward the gland can now be seen. At this point, if there is any adherence with the gland, a silk-catgut thread can be pulled back and forth as a saw in order separate the two. Once the glandular branch of the facial artery has been separated and detached from the gland, the submaxillary gland is fully removed. A small drainage is positioned in the surgical cavity sutured with Dexon thread and medicated with an external "Tensoplast" compress stretched from the jaw bone to the mastoid on the opposite side. The authors feel that the above surgical technique may prove advantageous and effective when a satisfactory esthetic result is required in benign submaxillary gland pathology. PMID- 1897373 TI - [Melanoma metastatic to the trachea and nasal cavity: description of a case and review of the literature]. AB - Secondary tumors of the trachea are exceedingly rare, only 14 cases having been reported in the literature. Moreover, metastatic involvement of naso-paranasal cavities can be considered quite unusual. Approximately 150 cases have been drawn from the literature, most of which presented a metastatic deposit from a renal adenocarcinoma. Report is then made of a case of cutaneous melanoma metastatic to the trachea and nasal cavity. The tracheal lesion was repeatedly treated with Nd Yag laser, whereas no treatment was considered eligible for nasal metastasis. The patient succumbed to the tumor 16 months after diagnosis of tracheal involvement had been made. The tendency for malignant melanomas to metastasize to distant organs via the bloodstream is well known, yet trachea and nasoparanasal involvement by metastatic melanoma has been reported, respectively, in only three and six cases, including the present one. Prognosis is unfavorable due to the unusual coexistence of metastases to other organs and the lack of an adequate treatment. PMID- 1897374 TI - Depressive disorders and dementia: the clinical view. AB - The relationship between depression and dementia is complex. Transient emotional disturbances and long-lasting depressive disorders may occur as psychological reactions to the loss of mental abilities or as behavioural manifestations of brain injury. On the other hand, major depressive disorder of late onset or of a recurrent type may be superimposed on dementing illness. Depression, particularly in elderly individuals, can manifest itself as a reversible syndrome of dementia that responds favourably to antidepressant treatment. It is not known whether the dementia syndrome of depression represents a quantitative intensification of minor cognitive impairments that can be observed in a large proportion of depressed patients. It also remains doubtful whether dementia in depressed patients has to be considered as an epiphenomenon of pervasive melancholic illness. An alternative explanation would look at such conditions as manifestations of a specific brain dysfunction. Major depression associated with cognitive impairment in stroke patients might be regarded as an example of a reversible dementia dysfunction. PMID- 1897375 TI - Cholinergic strategies in the treatment of Alzheimer's disease. AB - Since the identification of the cholinergic deficit, strategies aimed at enhancing cholinergic neurotransmission have dominated the field of pharmacology in Alzheimer's disease (AD). These strategies include increasing acetylcholine precursor availability, delaying synaptic degradation and stimulating muscarinic receptors. Although most clinical trials report mild symptomatic improvements in some patients, support for large-scale clinical use of cholinomimetics in AD is not yet available. This article presents the most representative clinical trials, discusses the limitations of the cholinergic strategies and suggests future directions in the treatment of AD. PMID- 1897376 TI - Cholinergic drugs as diagnostic and therapeutic tools in affective disorders. AB - The hypothesis of a significant involvement of the cholinergic system in the pathogenesis of affective disorders still lacks strong experimental support. This is mainly because of missing specific peripheral markers of the central nervous activity of the cholinergic system and the lack of specific cholinergic agonists and antagonists without severe peripheral side effects. As the direct cholinergic agonist RS 86 seems to be more suitable because of its minor side effects, long half-life and oral applicability, it was tested for its antimanic property and its effect on the hypothalamo-pituitary adrenal system and the rapid eye movement (REM) sleep-generating system. RS 86 exhibited antimanic and REM sleep-inducing properties, but failed to stimulate the cortisol system. PMID- 1897377 TI - Physostigmine in Alzheimer's disease: effects on cognitive functioning, cerebral glucose metabolism analyzed by positron emission tomography and cerebral blood flow analyzed by single photon emission tomography. AB - The effect of acute, intravenous administration of physostigmine on measures of brain activity and cognitive functioning were investigated in 14 patients with Alzheimer's disease. Regional cerebral glucose metabolism was assessed using (18F)-fluoro-2-deoxy-D-glucose and positron emission tomography, and cerebral blood flow was assessed using 123I-iodoamphetamine single photon emission tomography. Although physostigmine enhanced cerebral blood flow in most patients, only one patient showed significant clinical improvement. This patient, however, also showed a very pronounced improvement in cerebral glucose metabolism. It is concluded that these preliminary findings hold considerable promise for our appreciation of the pathophysiology of dementing illness as well as our understanding of centrally acting compounds of interest in Alzheimer's disease. PMID- 1897378 TI - Cholinergic drugs, affective disorders and dementia: problems of clinical research. PMID- 1897379 TI - Prevalence of problem behavior in Dutch children aged 2-3. AB - The present study provides prevalence data on behavioral and emotional problems in Dutch preschool children from the general population. The Child Behavior Checklist for ages 2-3 (3) was completed by parents of 421 children aged 2-3 living in the Dutch province of Zuid-Holland. Mean 3-week test-retest reliability of the instrument was .79 (pearson correlation) and the mean interparent agreement was .47. The CBCL/2-3 scores correlated positively and significantly (mean r of .65) with the BCL, an instrument designed to measure behavior problems, and not substantially (mean r of -.06) with the MCDI, an instrument to assess the child's level of general development. For each of the 99 problem items the prevalence rates were presented graphically for boys and girls in 6-months age-groups. The prevalence rates of individual problem items ranged from 1% to 80%. Sixteen percent of the items was scored for more than half of the sample, indicating that the behavior covered in these items may be quite common in young preschool children. In this sample 7.8% of the children were estimated to have a behavior problem, which compares well to the rates found in other studies. No age, sex, or SES differences in total problem scores were found. Almost all significant age, sex, and SES differences found for individual items were small. Age differences found for individual problem items probably reflect the growing self-other differentiation in 2-3-year-olds. Analysis of sex differences revealed that boys were rated to be more aggressive and oppositional and as having more developmental problems, and that girls were rated to have more sleep problems. SES differences were found for items which reflect hyperactive, undercontrolled, dependent, and depressed behaviors. Comparison of problem scores for referred and nonreferred preschool children indicated higher scores for referred children on 72 of the 99 problem items. The largest differences were found for the items Doesn't get along with other children, Wants a lot of attention, and Can't concentrate. Based on the total problem score 70 percent of the children could be correctly classified as referred or non-referred. A large percentage of children, however, was incorrectly classified based on the total problem score alone. PMID- 1897380 TI - Levels of serum steroid hormones in intrauterine contraceptive device users. AB - Serum progesterone, estradiol, testosterone and cortisol were assayed in the mid follicular and mid-luteal phases of the menstrual cycles in 30 Lippe's loop and 30 Cu T-200 IUCD users, compared to 24 controls. Mean serum progesterone and estradiol levels were significantly higher in the mid-luteal, compared to the mid follicular phase in each group (p less than 0.01). There were no significant differences between the mean levels of progesterone, testosterone and cortisol in IUCD users and controls in both the mid-follicular and mid-luteal phases. IUCD users had significantly higher levels of estradiol (p less than 0.01) in the mid luteal phase but not in the mid-follicular phase, compared to controls. There was hormonal evidence of corpus luteum insufficiency in 8.3%, 14.3% and 20% in the controls, Lippe's loop and Cu T-200 IUCD users, respectively. PMID- 1897381 TI - Ovarian development and sex steroid hormones during the reproductive cycle of Podarcis s. sicula Raf. AB - Variations in ovary weight and seasonal changes in plasma androgens, 17 beta estradiol and progesterone have been studied during the reproductive cycle of female Podarcis s. sicula Raf. Adult female Podarcis were captured in the surroundings of Naples during the years 1988 and 1989. Ten lizards were sampled monthly (except in February, August, October and December). Ovaries and oviducts were submitted to morphological examination, and in the blood samples androgens, 17 beta-estradiol and progesterone were assessed by the radioimmunoassay (RIA) method. Ovary weight, expressed as the gonadosomatic index (GSI), presented two statistically significant peak values in April and June, related to the ovulatory waves observed in this study. Several shelled oocytes were also found in the oviducts in this period. Progesterone titers mirrored the modifications of GSI and a very significant correlation (p less than 0.001) between the two parameters can be ascertained. Androgens increased in early spring, peaked in April, and low levels of androgens were found in September and during the winter months. Estradiol titers reached the peak values in March, and, after a sharp decrease in April, remained high until the winter months. The results reported here substantiate the periovulatory changes of the three major gonadal steroids during the annual ovarian cycle of Podarcis s. sicula. PMID- 1897382 TI - Protective effect of fungal growth product (6MFA), assessed therapeutically against Ehrlich's ascites tumor in Swiss mice. AB - 6MFA is a growth product of the fungus Aspergillus ochraceus (ATCC 28706) obtained by fermentation in stationary culture. It has both interferon inducing and antiviral properties, in vivo and in vitro, with a relatively high margin of safety (9, 17, 18). Ehrlich's ascites tumor bearing Swiss albino male mice were treated with 0.5 ml of acqueous preparation of 6MFA (0.75 mg total solids) i.p. in a therapeutic regimen schedule; the sham treated mice received only PBS. 6MFA treatment produced an increase in mean survival time over the untreated controls, restricted the body weight increase due to ascites and decreased the rate of mortality. As much as 100% of survival response was obtained in the group treated with 0.5 ml of 6MFA at the rate of one inoculation per week for 5 weeks. In general a dose-dependent response was seen in the antitumor effect of 6MFA against Ehrlich's ascites tumor in Swiss mice. Delay in administration of 6MFA to tumor bearing mice affected the survival rate. PMID- 1897384 TI - Food safety assurance: the European perspective. PMID- 1897383 TI - Induction of colony-stimulating factors by Plasmodium cynomolgi components. AB - Plasmodium cynomolgi total parasite antigens soluble in culture medium (P.c.SA), when injected in monkeys (Macaca mulatta) intravenously, induced the synthesis and secretion of serum colony-stimulating factors (CSFs). In vitro cultured monkey splenic macrophages and blood monocytes, following incubation with P.c.SA, also elaborated CSFs: the splenic macrophages responded more. Peak CSFs levels, both in vivo and in vitro, were attained after 8 hours of P.c.SA stimulation, and thereafter declined to baseline values within 48 hours. CSFs, both in serum and in conditioned medium, induced the formation of macrophage, granulocyte and granulocyte-macrophage colonies in vitro, in the same proportion, indicating that committed progenitor cells responded to CSF from both sources in a similar way. Polymyxin B treatment had no effect on P.c.SA stimulated CSF elaboration by macrophages, suggesting an LPS-independent mechanism of CSF induction. CSF synthesis appeared to be de novo, as cycloheximide treatment of macrophages completely inhibited CSF production. These observations indicate that P. cynomolgi components can induce CSF synthesis. PMID- 1897385 TI - Formation of heterocyclic amines during meat extract processing and cooking. AB - Standardized biological in vitro systems and in particular those used for cancer prediction are being used to monitor the development of food products in order to ensure the absence of potential mutagens or carcinogens. Maillard reactions occurring during meat extract production was followed in order to reduce the formation of heterocyclic amines. Possibilities to reduce the content of heterocyclic amines during meat extract processing have been proposed. However, several aspects, such as interaction with food-borne mutagen or carcinogen inhibitors, keeping quality, and organoleptic properties have also been taken into consideration. Whenever possible, food contaminants must be analytically determined and compared to total intake exposure and tolerated levels of other comparable food contaminants to establish realistic "tolerated" contamination levels. PMID- 1897386 TI - Wholesomeness and safety of irradiated foods. AB - Irradiation with gamma-rays, X-rays or fast electrons can be used to change foodstuffs in beneficial ways or to destroy harmful organisms. Gamma rays do not induce radioactivity in foods, but X-rays and fast electrons can induce short lived radioactivity if sufficiently energetic. This imposes limitations on the energies which can be used, and a short wait between irradiation and consumption may be advisable. Irradiation produces chemical changes in foodstuffs, and some foods are unsuitable for irradiation. With appropriate foods, trials with animals and human volunteers generally show that the product is safe. Some loss in nutritional quality can take place, which could be significant for some individuals, but are unlikely to be important for those on a balanced diet. Irradiation does not eliminate all risk from microbial contamination. Foods to be irradiated should be good quality, and need to be kept under proper conditions after irradiation. Irradiated foods should be appropriately labelled. Tests for radiation would help to enforce necessary controls. If the process is properly carried out on appropriate foods, and all due precautions are taken, irradiated foods are wholesome and safe. PMID- 1897388 TI - Mutagens and carcinogens in cooked foods: concentration, potency, and risk. PMID- 1897387 TI - An experimental approach to identifying the genotoxic risk by cooked meat mutagens. AB - In order to define the toxicological risk for the human population derived from the chemical compounds formed during the process of cooking animal meat, which have been described to possess a mutagenic, genotoxic, and carcinogenic activity, an extensive study has been developed on cooked meat extract and two cooked meat mutagens, IQ and MeIQx. The study has been based on toxicokinetics and mouse tissue distribution of the two chemicals, on in vitro and in vivo mutagenicity/genotoxicity analyses (gene mutation, chromosome aberration, micronuclea in mouse bone marrow cells, mice urine and faeces mutagenicity test), as well as in vivo protein and DNA binding. The two chemicals have been found positive for the induction of gene mutation on Salmonella, but not in V-79 Chinese hamster cells; IQ only has been found positive for the induction of chromosome aberrations on CHO cells and cultured human lymphocytes. IQ and MeIQx were negative for the induction of micronuclea in mice treated with 40 mg/kg of the chemicals; the lowest effective administered dose to the mice which produced mutagenic urine was 0.4 mg/kg of IQ and 0.04 mg/kg of MeIQx. A dose of 40 mg/kg of IQ given by gavage to mice produced an excretion of 1-4% of the applied dose in the urine and 0.1-2% of the applied dose in the faeces, when evaluated chemically or mutagenically. The DNA adducts for the liver were correlated with the dose of the IQ and MeIQx administered to the mice. All the data have been used for defining a possible risk estimate derived to the human population as a consequence of a cooked meat diet. PMID- 1897389 TI - Beef supernatant-fraction-based studies of heterocyclic amine-mutagen generation. PMID- 1897390 TI - Modification of carcinogen metabolism by indolylic autolysis products of Brassica oleraceae. AB - Cruciferous plant foods contain large quantities of secondary plant metabolites that have been shown to inhibit chemically induced carcinogenesis in animals. One mechanism by which these chemicals may inhibit carcinogenesis is through the induction of enzymes, such as cytochrome P-450-dependent monooxygenases, glutathione S-transferases (GST) or epoxide hydrolases (EH), which metabolize carcinogens to more polar and excretable forms. Cruciferous vegetables of the Brassica genus (e.g. Brussels sprouts, cauliflower, broccoli) contain micrograms/g levels of an indolylmethyl glucosinolate commonly known as glucobrassicin. Upon disruption of the plant material, as in food preparation or chewing, a thioglucosidase-mediated autolytic process ensues generating indole-3 carbinol (I3C), glucose, and thiocyanate ion. At acid pH comparable to that found in the stomach, I3C forms to wide variety of condensation products ranging from linear and cyclic dimers, trimers and tetramers to extended heterocyclic compounds such as indolocarbazoles. Experiments reviewed here indicate that these indole-condensation products are the compounds responsible for some of the alterations in carcinogen metabolism observed in animals fed either I3C or any of several Brassica plant foods. PMID- 1897391 TI - Dietary modulation of the glutathione detoxification pathway and the potential for altered xenobiotic metabolism. AB - This review summarizes the literature regarding nutritional regulation of the pathways of glutathione synthesis and subsequent conjugation of xenobiotic compounds. The glutathione detoxification pathway includes the enzymes of the gamma-glutamyl cycle as well as sulfur conjugation reactions. This promotes bodily excretion of xenobiotics as well as normal metabolites. Regulation of intracellular glutathione concentrations is maintained largely through changes in the activity of gamma-glutamylcysteine synthetase. Availability of glutathione for detoxification purposes can be limited by the supply of intracellular cysteine to serve as a precursor for glutathione synthesis through the gamma glutamyl cycle. Dietary methionine, cysteine and cysteine prodrugs have been examined for their potential to maximize glutathione availability for detoxification purposes. Some xenobiotic challenges have been reported to deplete hepatic glutathione reserves and toxicity correlates with the degree of depletion. Other foreign compounds, however, have been observed to increase cellular glutathione concentrations beyond normal levels despite regulation of the synthetic pathway. Such effects will be reviewed. PMID- 1897392 TI - Prevention of adverse effects of food browning. AB - Amino-carbonyl interactions of food constituents encompass those changes commonly termed browning reactions. Such reactions are responsible for deleterious post harvest changes during processing and storage and may adversely affect the appearance, organoleptic properties, nutritional quality, and safety of a wide spectrum of foods. A growing area of concern is nutritional carcinogenesis, in which nutritionally linked cancer has been associated with amino-carbonyl reaction products. Specific practical and theoretical approaches to prevent adverse effects of food browning include: (1) modification and removal of primary reactants and endproducts in the browning reaction; (2) prevention of deleterious browning reactions through the use of antioxidants; (3) blocking of in vivo toxicant formation from browning products by means of dietary modulation; (4) accurate estimation of low levels of browning products in whole foods and their removal through antibody complexation; and (5) stimulation of inactivation in vivo toxicants from browning products by use of amino acids and sulfur-rich proteins. PMID- 1897393 TI - Inhibition of browning by sulfites. AB - The present state of understanding of the mechanisms by which sulfites inhibit browning reactions in food is reviewed. The difficulties of specifying the composition of sulfur(IV) oxospecies in sulfited foods arise from the existence of labile equilibria between SO2, HSO3-, SO3(2-) and S2O5(2-), whose position depends on concentration, ionic strength and the presence of non-electrolytes. A proportion of the additive is also found in a reversibly bound form. The main reason why sulfites are able to inhibit a wide range of browning reactions is the nucleophilic reactivity of sulfite ion. The mechanism of reactions between sulfite species and intermediates in the model Maillard browning reaction, glucose + glycine, are considered in depth and are supported by kinetic data. A most interesting feature is the fact that sulfites seem to catalyse the reactions they are added to control. Reaction products include 3,4-dideoxy-4 sulfohexosulose which is formed initially and polymeric substances arise from the reaction of sulfite species with melanoidins. It is found that melanoidins from glucose + glycine react with sulfite to such an extent that one sulfur atom is incorporated for every two glucose molecules used to make up the polymer. The mechanisms of inhibition of ascorbic acid browning, enzymic browning and lipid browning are reviewed briefly. The known toxicological consequences of the formation of reaction products when sulfites are used for the control of Maillard browning give little cause for concern. Little is known of the implications of the formation of reaction products during the inhibition of other forms of browning. Consideration of the requirements for alternatives to sulfites is given. PMID- 1897394 TI - Dietary n-3 polyunsaturated fatty acids of fish oils, autoxidation ex vivo and peroxidation in vivo: implications. PMID- 1897396 TI - Residue trypsin inhibitor: data needs for risk assessment. AB - Trypsin inhibitor (TI) occurs naturally in many foods from plants, notably soybean protein products. Heat treatment inactivates TI and improves nutritional quality, but residual TI activity of 5 to 20% remains after typical commercial treatments. Chronic feeding of TI or products that contain TI can inhibit trypsin and chymotrypsin, stimulate their secretion, cause hypertrophy and hyperplasia of the pancreas, and lead to adenomas and carcinomas of the exocrine pancreas. In the rat, TI promotes pancreatic carcinogenesis initiated by azaserine. Data needed for possible risk assessment on TI would include 2-year bioassays from animals treated with TI and fed diets carefully controlled for type and amount of fat (which also promotes pancreatic carcinogenesis). The effects of TI on protein nutrition would have to be considered when identifying the maximum tolerated dose. Major reductions in human dietary TI exposure may not be feasible because of the multiple sources of TI, the substantial promotion by other factors such as fat, and the adverse effects of excessive heat on food products. For risk assessment of TI in a particular food, other promotors and the feasibility of decreasing TI intake must be considered. PMID- 1897395 TI - Formation and action of anticarcinogenic fatty acids. AB - Conjugated dienoic derivatives of linoleic acid (referred to by the acronym CLA) constitute a newly recognized class of anticarcinogenic fatty acids. Of the eight major CLA isomers, the cis-9, trans-11 isomer alone is incorporated into phospholipid and may be the most biologically relevant isomer. CLA exhibits potent antioxidant activity; evidence is presented indicating that CLA acts both as an in vitro and in vivo antioxidant. The formation of CLA in foods, and its possible biological significance in cell membranes, is discussed. PMID- 1897397 TI - Studies of food allergens: soybean and egg proteins. PMID- 1897399 TI - Reduction of whey protein allergenicity by processing. PMID- 1897398 TI - Identification of soy protein allergens in patients with atopic dermatitis and positive soy challenges; determination of change in allergenicity after heating or enzyme digestion. PMID- 1897400 TI - A light-induced tryptophan-riboflavin binding: biological implications. AB - We review here the covalent photo-binding induced by visible light between the essential amino acid tryptophan and the vitamin riboflavin. We discuss the biological implications of this photoadduct in relation to the hepatotoxic and cytotoxic effect associated to parenteral nutrients and to culture media exposed to the action of light, respectively. We also analyze the formation of a photo binding between riboflavin and the residues of tryptophan present in the proteins of the eye lens, a tissue which is permanently exposed to visible light. PMID- 1897402 TI - Digestibility of processed food protein. AB - An overview is given on the effects of food processing on the protein digestibility. Beneficial effects of food processing are primarily observed in a range of plant foods containing toxic substances and/or anti-nutrients (legumes, cereals, some seed food). Digestibilities improve by heating, soaking, germination and fermentation. These processing steps reduce the amount of active enzyme inhibitors through extraction, inactivation by heat or microorganisms, or by compositional modification through germination. Reduced protein digestibility is primarily associated with excessive heat, exemplified by the comparatively low digestibility of ready-to-eat breakfast cereals. Experiments with model systems indicate that some caution should be observed with the use of alkalis in food processing, and with products prone to the Maillard reaction. PMID- 1897401 TI - Effect of heat on the nutritional quality and safety of soybean cultivars. AB - To evaluate whether soybean strains with reduced levels of trypsin inhibitors have enhanced nutritional and safety characteristics, we measured protease inhibitor content of a standard cultivar (Williams 82) and an isoline (L81-4590) lacking the Kunitz trypsin inhibitor, using enzyme inhibition assays and enzyme linked immunosorbent assays (ELISA). Less heat was needed to inactivate the remaining trypsin inhibitory activity of the isoline than that of the standard soybean cultivar. In fact, autoclaving (steam heating at 121 degrees C) of the isoline for 20 min resulted in a near zero level of trypsin inhibitor activity, while 20% remained in the Williams 82 sample. Feeding studies with rats showed that the raw soy flour prepared from the isoline was nutritionally superior to the raw flour prepared from the standard variety, as measured by PER and pancreatic weights. Since the content of amino and fatty acids of the flours from both strains was identical and the hemagglutinating activities were within a factor of 2, the increased PER was likely due to the lower level of trypsin inhibitory activity in the isoline. Steam heating the flours for up to 30 min at 121 degrees C progressively increased the PER for both strains. Preliminary screening of several accessions from the USDA Soybean Germplasm Collection showed considerable variation in the content of trypsin inhibitors, sulfur amino acids, and lectins. The BBI content of these cultivars, determined by chymotrypsin inhibition assays, was identical to that found by ELISA. The results indicate that further screening studies could lead to the discovery of soybeans which yield flour that is safe and nutritious, with minimal need for heating. PMID- 1897403 TI - Amino acid ratings of different forms of infant formulas based on varying degrees of processing. AB - Amino acid profiles, protein digestibility and/or amino acid bioavailability for the various forms (powder, liquid concentrate, ready-to-use, etc.) of infant formulas (involving varying degrees of heat processing during preparation) have been determined. Amino acid scores (based on the single most limiting amino acid) were calculated by comparing the essential amino acid data with that of human milk. Amino acid scores were multiplied by total protein (g/100 kcal) to obtain amino acid ratings, which take into account both quality and quantity of protein. Amino acid scores for milk- and soy-based formulas ranged from 49 to 90 and 59 to 81%, respectively, due to deficiencies in methionine plus cystine and/or tryptophan. The deficiency in the limiting amino acids was more marked in liquid concentrate than powder prepared by the same manufacturer. Because of significantly higher total protein contents (g/100 kcal) of soy- (2.65-3.68) and milk-based (2.20-2.95) formulas compared to human milk (1.5), the relative amino acid ratings (human milk = 100) of all formulas except two milk-based liquid concentrates and one ready-to-feed (with values of 77-87%) were greater than 100%. When corrected for protein digestibility, the relative amino acid ratings for all four liquid concentrates were less than 100%. Lower levels of digestible protein and bioavailable amino acids in liquid concentrate compared with powder (prepared by the same manufacturer) would suggest that inferior protein quality of liquid concentrates may be due to more severe heat treatment involved in their preparation. PMID- 1897404 TI - Formation, nutritional value, and safety of D-amino acids. AB - The extent of racemization of L-amino acid residues to D-isomers in food proteins increases with pH, time, and temperature. The nutritional utilization of different D-amino acids vary widely, both in animals and humans. In addition, some D-amino acids may be deleterious. For example, although D-phenylalanine is nutritionally available as a source of L-phenylalanine, high concentrations of D tyrosine inhibit the growth of mice. The antimetabolic effect of D-tyrosine can be minimized by increasing the L-phenylalanine content of the diet. Similarly, L cysteine has a sparing effect on L-methionine when fed to mice; however, D cysteine does not. The wide variation in the utilization of D-amino acids is exemplified by the fact that D-lysine is not utilized as a source of L-lysine, whereas the utilization of D-methionine as a source of the L-isomer for growth is dose-dependent, reaching 76% of the value obtained with L-methionine. Both D serine and the mixture of L-L and L-D isomers of lysinoalanine induce histological changes in the rat kidneys. D-tyrosine, D-serine, and lysinoalanine are produced in significant amounts under the influence of even short periods of alkaline treatment. Unresolved is whether the biological effects of D-amino acids vary, depending on whether they are consumed in the free state or as part of a food protein. Possible, metabolic interaction, antagonism, or synergism among D amino acids in vivo also merits further study. The described results with mice complement related studies with other species and contribute to the understanding of nutritional and toxicological consequences of ingesting D-amino acids. Such an understanding will make it possible to devise food processing conditions to minimize or prevent the formation of undesirable D-amino acids in food proteins and to prepare better and safer foods. PMID- 1897405 TI - Effect of food processing and preparation on mineral utilization. AB - While effects of various nutrients and certain non-nutrient components of food on mineral utilization have been intensively studied, less is known about the effects of food processing and preparation procedures. Fermentation during the production of beer, wine, yogurt, and African tribal foods affects bioavailability of Zn and Fe. Baking affects the chemical form of Fe in fortified bread products and these changes can affect its bioavailability. Availability of Fe in milk-based infant formula depends on whether Fe is added before or after heat processing. Food packaging (e.g., tin cans) can alter food composition and thus potentially affects mineral bioavailability. Maillard browning has been reported to cause slight decreases in Zn availability both in vitro and in humans. However, we found that feeding of highly browned casein-glucose products to rats as 5% of diet produced no effect on Zn absorption (59.5 +/- 8.2% vs 54.1 +/- 7.3%) or Fe absorption (45.6 +/- 7.7% vs 46.9 +/- 12.6%) for browned vs control, respectively; nor did we find any of the adverse health effects reported by others. We found no effect on stable Zn or Cu absorption in seven men when browned foods were fed, compared to the same diets without browning. Zinc absorption was 34 +/- 13% (browned) vs 24 +/- 15% (unbrowned), and Cu absorption was 55 +/- 5% vs 55 +/- 8% (p greater than 0.05). PMID- 1897406 TI - Synthesis and availability of niacin in roasted coffee. AB - The coffee bean contains about 1% of trigonelline that is demethylated at temperatures approaching 200 degrees C; it is partially converted into nicotinic acid. This operation is mainly proportional to the severity of dry heat treatment; various other physico-chemical factors also influence the synthesis of niacin during the roasting. The niacin content of weakly roasted commercial coffee is about 10 mg/100 g (American coffee) and it reaches 40 mg in heavy roasted coffees, i.e. Italian coffee. Caffeine-free coffee is lower in niacin than the corresponding raw coffee. The drinking retains 85% of the niacin formed during roasting; it is totally available for the organism and can constitute a noticeable part of the daily supply in niacin. PMID- 1897407 TI - Anti-nutritive effects of dietary tin. AB - Tin is usually present in foods at levels of less than 4 micrograms/g. Higher levels may be found in some processed foods due to the addition of tin-based preservatives and stabilizers or to corrosion and leaching of the metal from unlacquered cans or from tin foils used in packaging. Estimates of dietary intake range from about 0.2 to greater than 5 mg Sn/day. Diets including a high proportion of canned vegetables and fish could supply greater than 30 mg Sn/day. Although intakes from dietary sources are generally considered to be harmless, a variety of adverse effects of tin have been reported, including effects on serum and bone alkaline phosphatase, lactic dehydrogenase, heme oxygenase, and 5 aminolevulinic acid dehydratase. Perturbations in glutathione metabolism have been reported, as have adverse effects on metabolism of essential trace minerals such as copper, zinc, and iron. Specific effects on calcium content of bone, serum, and kidney have also been described. Reported effects vary with the chemical form, dose of tin, and route and frequency of administration. Effects of tin in animal systems and on essential trace mineral absorption and excretion in human volunteers are reviewed. A summary of recent investigations on dietary tin copper interactions and effects of tin on rat hepatocellular antioxidant protection are also presented. PMID- 1897408 TI - Interaction between casein and vitamin A during food processing. AB - A particular relation exists between casein micelle and vitamin A. In vitro, large amounts of retinol are fixed to acid casein and its different fractions by hydrophobic bindings. The binding on the hydrophobic amino-acid residues (Trp, Phe) is greatly facilitated by a configurational change in the molecule exposed to physico-chemical parameters: alcalinity and heat treatments. Another amount of retinol is even more strongly fixed by a binding which can only be broken by saponification. Casein plays an important role in stabilizing retinol which does not degrade over time or during heat treatments. In vivo, when the retinol availability is measured by the vitamin A content in the liver, acid casein somewhat increases the retinol efficiency and, even more so, the retinal efficiency. Nevertheless, this favourable action is only observed under particular conditions: balanced diet, casein from milk, etc. For the moment, the animal data cannot be directly linked with the properties of binding appearing in vitro. PMID- 1897409 TI - Thermal degradation of carotenes and influence on their physiological functions. AB - Raw carrot juice contains a considerable amount of alpha- and beta-carotene, which makes carrot an excellent source of vitamin A. Heat treatment of the juice at temperatures comparable to those at pasteurization and boiling does not change the carotenes, while heating at temperatures used during sterilization results in rearrangement of the carotene molecules and a decrease in total carotenes. The all-trans alpha- and beta-carotenes appear partly as cis-isomers, especially the 13-cis-isomer. Isomerization of the carotenes leads to a decrease in their vitamin A activity. Carotenes also seem to be anticarcinogens but the extent to which this property is influenced by isomerization is still unknown. PMID- 1897410 TI - Formation of meat mutagens. AB - The formation of meat mutagens has been studied the last 10 years by carrying out modeling and meat cooking experiments in parallel. During this time, the list of meat mutagens has been growing, and continues to grow. The meat mutagens are usually produced in the crust of animal foods during frying, broiling, and baking. Another important source is meat extracts, consumed as gravies and meat bouillons. The formation of meat mutagens has been shown to depend physically on time, temperature, and water. Three major precursors have been identified: creatine or creatinine, certain amino acids, and monosaccharides or disaccharides. A requirement of sugar assumes a participation of the Maillard reaction, which also forms the basis for one of the major reaction mechanisms suggested. However, the meat mutagens are produced also in the absence of sugars, which means that other routes might be possible as well. Although the major precursors have been identified, more work needs to be done on the reaction mechanisms, the kinetics, and on the food constituents that might enhance or inhibit the formation of the meat mutagens. The results obtained to date point to several possibilities to control the formation of meat mutagens. PMID- 1897411 TI - Treatment of the particularly fatty neck and the short-interval secondary facelift. AB - In patients with normal body weight but with large accumulations of submental and cervical fat, good results can be obtained by an extensive subcutaneous dissection, carefully sculpted removal of the excess fat, and relatively limited work on the platysema. For some patients there may be an indication for a secondary facelift involving skin dissection alone within a relatively short interval. PMID- 1897412 TI - Comparison of the syringe and pump aspiration methods of lipoplasty. AB - In our study of six patients who underwent fat aspiration with a syringe on one side and with a pump on the other, there was notably less blood in the fat aspirate from the syringe and less bruising and morbidity in the postoperative period. The only variable in the study for each patient was the method of aspiration. PMID- 1897413 TI - Liposuction: more curettage than aspiration. AB - After infiltration with epinephrine solution in each adipose area, an 8- or 10-mm cannula, without the suction tube connected, was introduced. With a curettage maneuver and by directing the cannula upward, the fat began to come out spontaneously. After obtaining a considerable amount of fat, the suction tube was connected and the remaining fat tissue aspirated at low suction power (250 mm Hg). With this curettage maneuver adiposity of the abdomen, knees, and trochanteric areas can be reduced. However, in the back, buttocks, or thighs, where adiposity is more fibrous, aspiration is needed from the start in almost every case, but always at low-power suction. This procedure is indicated in particular for the face and neck and for secondary liposuction. The fact that fat comes out easily through the cannula (without suction) demonstrates that the curettage maneuver is more important than the aspiration. Only with curettage can a considerable amount of fat be removed. No fat is removed when aspiration of 1 atm without a curettage maneuver is used. Suction only helps to remove fat already mobilized and free in the cannula. Our experience includes 34 patients. PMID- 1897414 TI - A physicochemical approach to improving free fat graft survival: preliminary observations. AB - A different experiment approach to the problem of post-transplantation free fat graft resorption was evaluated. Bioactive free fat grafts were created through the addition of basic fibroblast growth factor (bFGF) carried on positively charged, hydrophilic, dextran beads to the grafts. This bioactive graft was compared with contralateral free fat grafts in the lateral facial areas of mature rats. After 90 days, when compared with the body mass increase of the animals, complete retention of the bioactive fat grafts occurred in contrast to the free grafts that exhibited loss of nearly half of their original weight. The histologic findings of small-sized adipocytes or adipocyte buds among larger adipocytes in the bioactive grafts raise the possibility of activation and induced differentiation of a preadipocyte cell line in these grafts. PMID- 1897415 TI - Resection of the buccal fat pad in the treatment of hypertrophy of the masseter muscle. AB - Partial resection of the buccal fat pad added to the resection of the masseter muscle clearly improves the results in hypertrophy of these muscles. PMID- 1897416 TI - Mycobacterial infection following blepharoplasty. AB - A case of exceedingly rare mycobacterial infection following blepharoplasty is recorded. This nursing home employee underwent a combined blepharoplasty, eyelid ptosis correction, and replacement of breast implants. One month later, she developed localized abscesses of both eyelids. Cultures revealed nontuberculous mycobacterial infection. The infection was controlled after ten months of antibacterial therapy using doxycycline. We believe that the patient's exposure to debilitated individuals due to her nursing profession and the presence of a Jones tube in the right lacrimal system were major contributing factors. PMID- 1897417 TI - The use of polytetrafluoroethylene for particular augmentation of the nasal dorsum. AB - In 24 cases scutiform polytetrafluoroethylene patches were implanted to correct saddle malformation and irregularities of the nasal dorsum. For smaller tissue defects of the nasal bone and cartilage, the patches are very suitable in rhinosurgery. One of the advantages of the implant is that it makes the reconstructed area appear as natural as possible. PMID- 1897418 TI - Cartilage chips synthesized with fibrin glue in rhinoplasty. AB - A new type of cartilage graft that is synthesized from cartilage fragments minced by our instrument and mixed with fibrin glue is described. This new material is useful when particular grafts are required in primary or secondary rhinoplasty. PMID- 1897419 TI - Comparative study of dermabrasion, phenol peel, and acetic acid peel. AB - Six areas of the face and forehead of a 36-year-old white female presenting with a benign congenital blue nevus of the skin were treated by dermabrasion, bichloracetic acid, and the classic phenol peel. Comparative results at six months showed each of these methods to be approximately equal in the depth of penetration and in the quality of skin on healing. However, in these small test sites, dermabrasion appeared to remove pigment slightly more efficiently. Therefore, her forehead and cheeks were treated with dermabrasion and subsequently with chemical peel. An attempt was made to touch up the dermabraded areas with acetic acid. Full thickness burns occurred, which resulted in thick scarring that required many months to finally heal. We conclude that at least in the treatment of pigmented lesions, the modalities of phenol, acetic acid, and dermabrasion are approximately equal. PMID- 1897420 TI - A systematic aesthetic approach to primary closure of the donor site following transposition of vertical forehead flaps. AB - Twenty patients underwent transposition of a vertical forehead flap to correct defects of the middle third of the face. The treatment and results are reported and evaluated. Based of the width of the secondary forehead defect, the best technique of direct closure was determined. Simpler cases were resolved by careful application of the basic techniques of plastic surgery--undermining and scalp flap rotation. When a forehead defect larger than 4.5 cm was expected, previous forehead skin expansion seemed advisable. A primary, tension-free suture of the forehead defect was achieved in every case, thus significantly improving the aesthetic outcome of the operation. PMID- 1897421 TI - Personal refinements in the single pedicle Skoog technique for reduction mammaplasty. AB - A review of the Skoog technique for reduction mammaplasty is presented. A laterally based single pedicle is used for transposition of the nipple-areola flap, deriving its blood supply from a cutaneous vasculature. From our experience using this procedure in a majority of patients, we have developed specific refinements starting with the preoperative planning and including various modifications in the operative technique. The advantages of these refinements are discussed as well as their contribution to the final aesthetic result. PMID- 1897422 TI - Pattern for reduction mammoplasty that uses a superior vertical dermal pedicle. AB - A new surgical planning pattern is described that permits application of the "coning principle" of the regional tissue after mammary reduction. It makes use of a superior vertical dermal pedicle for nourishing the nipple-areola complex. The pedicle is not connected to the subjacent mammary tissue and thus can be folded over itself to accommodate the nipple-areola area at its new position. PMID- 1897423 TI - A new scalp flap for baldness. AB - The technique and results of a new scalp flap that solves frontal baldness are described. As a bipediculate flap it offers a great amount of hair when advanced and has a low rate of complications. This kind of flap has been used by us for four years in 36 patients in the age group between 20 and 60 years. The results obtained with the flap have been very satisfactory. PMID- 1897424 TI - The European Histamine Research Society, nineteenth annual meeting. May 16-20, 1990, Kuopio, Finland. PMID- 1897425 TI - Kainic acid-induced changes in histamine-immunoreactive nerve fibers in the rat brain. AB - Histamine is found in neurons and their long projections in the mammalian brain. The mammalian histaminergic system consists of nerve cell bodies in the tuberomammillary nucleus, and extensive, crossing projections to various brain areas. In addition to the tuberomammillary histaminergic system, histamine is found in rhombencephalic neurons during fetal development of rat. To investigate if histamine has a function in growth and regeneration of the nervous system, small injections of kainic acid were made into different parts of the rat brain. Histamine-immunoreactive nerve fibers were seen in and around the lesions 2 to 15 weeks after the injection. The density of these fibers was higher than that of the control side. The results suggest that histamine is either accumulated in pre existing fibers or that sprouting of histamine-containing nerves is induced by the lesions. The newly established in situ hybridization method for the enzyme histidine decarboxylase may reveal possible dynamic changes in enzyme regulation associated with the lesions. PMID- 1897426 TI - Neurofibrillary tangles and histamine-containing neurons in Alzheimer hypothalamus. AB - The location of histamine-immunoreactive (IR) cell bodies in normal aged human brain and in cases of Alzheimer's disease (AD) were compared to the distribution of neurofibrillary tangles (NFT). Cryostat sections were fixed with carbodiimide and processed for histamine-immunohistochemistry using the PAP technique. NFT were visualized in the same sections using thioflavin. Histamine-IR cell bodies in human brain were concentrated in the tuberomammillary (TM) nucleus that embodied a major part of the hypothalamus. Although located in similar large profiles and mainly concentrated in the TM area, the numerous hypothalamic NFT in AD were seldom found within the histamine-IR neurons. PMID- 1897427 TI - Distribution of histamine in the developing peripheral nervous system. AB - The presence and ontogenetic distribution of histamine was studied in the developing peripheral nervous system of the rat by using an indirect immunofluorescence technique and a specific rabbit anti-histamine antiserum. Histamine immunoreactivity (IR) first appeared in peripheral nerves on embryonic day 14. The number and intensity of histamine-immunoreactive nerves was highest on embryonic days 16-18. During development starting from embryonic day 14, motoneurones in ventral horns of the spinal cord at cervical, thoracic and lumbar levels contained histamine IR. A subpopulation of sensory neurones in dorsal root ganglia exhibited histamine IR. Histamine IR was also present in nerve fibres of ventral and dorsal roots of spinal cord, as well as in spinal nerves. Population of neurons and nerve fibres in sympathetic and pelvic ganglia as well as in myenteric ganglia of the intestine were also labelled with the histamine antiserum. In peripheral target organs, histamine IR was observed in nerve fibres around bronchi of the lungs, in the atria of the heart, in the adrenal gland, in the intestinal wall, in muscular tissues and in subepithelial tissue of the skin. The results of this study indicate that histamine is widely distributed in different types of neurons and nerve fibers of the developing peripheral nervous system. PMID- 1897428 TI - Histamine in the nervous system of Macoma balthica (Bivalvia). AB - The distribution of histamine(HA)-immunoreactivity of the molluscan species Macoma balthica was mapped with an antiserum against a histamine-protein conjugate. The main ganglia of the central nervous system of M. balthica, the cerebropleural ganglia, the pedal ganglion and the visceral ganglion all contained strongly HA-positive fluorescent cell bodies. The positive cell bodies were situated in clusters in the outer region of the ganglia. Immunoreactive fibres were located in the inner neuropil region of the ganglia. Also the commissure and the connectives of the ganglia as well as many nerve roots contained HA-positive fibres. These results agree well with the recent finding of the wide distribution of histamine in the nervous system of two marine gastropod molluscs, Aplysia and Pleurobranchaea supporting the thought that histamine has an important role in many physiological function of molluscs. PMID- 1897429 TI - Inhibition of histamine synthesis influences the development of hypertension in spontaneously hypertensive rats. AB - Young (3-week old) and adult (7-week old) spontaneously hypertensive rats (SHR) and normotensive rats (WKY) were treated with alpha-fluoromethylhistidine (alpha FMH) for 29 and 13 days, respectively. Treatment of SHR and WKY with alpha-FMH led to a pronounced decrease in the histidine decarboxylase activity and in the histamine concentration in all brain areas studied. In adult SHR, the development of hypertension was not influenced by alpha-FMH. In young SHR, alpha-FMH elicited a transient delay in the development of hypertension followed by a short-lasting tendency for increased blood pressure. It is concluded that histaminergic neurons of the brain play, if at all, only a secondary role in the development of hypertension in SHR. PMID- 1897430 TI - Histidine decarboxylase inhibition induced by alpha-fluoromethylhistidine provokes learning-related hypokinetic activity. AB - The influence of brain histamine (HA) on learning and memory is not well understood, although some reports indicate that HA improves memory consolidation. We have studied the effects of alpha-fluoromethylhistidine (FMH) (100 mg/Kg, i.p.), which reduced by 60-80% the concentration of hypothalamic HA, on rat locomotor activity (LA) and learning in several experimental conditions in a computerized system. FMH reduced LA in an open field paradigm (OFP) 3 h after injection and tended to inhibit motor habituation after a 3-day trial. In a maze paradigm (MP), where the animals had to learn to avoid a foot-shock (1 mA), FMH reduced LA, rearing (2F), and jumping activity (JA). The peripheral administration of HA to control-trained rats reduced a learning index (N/Sts ratio) by 50%. According to these results, FMH diminished LA, 2F, and JA with no effect on habituation in MP. These observations might indicate that a moderate reduction in the levels of brain HA might enhance attention in solving visuo spatial tasks under stressful stimuli. PMID- 1897431 TI - Pharmacological characteristics of catalepsy induced by intracerebroventricular administration of histamine in mice: the importance of muscarinic step in central cholinergic neurons. AB - Histamine-induced catalepsy was antagonized potently by scopolamine, an antimuscarinic drug, and partially blocked by sparteine. Neither methylatropine nor antinicotinic drugs could reverse histamine-induced catalepsy. These results indicate the greater importance of muscarinic receptors rather than their nicotinic counterparts in histamine-induced catalepsy. Various antiparkinson drugs, i.e. biperiden and trihexyphenidyl, which have antimuscarinic activity or dopamine agonists, i.e. L-dopa, amantadine and bromocriptine, could antagonize the histamine-induced catalepsy to various degrees. Thus, catalepsy induced by icv histamine can be evoked not only by an activation of the histamine receptor, but also indirectly due to cholinergic and dopaminergic imbalance. PMID- 1897433 TI - Effect of a single dose of TCDD on the level of histamine in discrete nuclei in rat brain. AB - Histaminergic neurones may be involved in the regulation of feed intake. Since TCDD causes anorexia in rats, histamine concentrations were measured in several hypothalamic nuclei involved in feeding regulation. Histamine concentrations were not changed in medial or lateral accumbens, suprachiasmatic, paraventricular, arcuate, ventromedial, dorsomedial or perifornical nuclei, or in lateral hypothalamic area, cortex, or pineal gland. There was, however, an increase in histamine concentration in median eminence 25 h after the administration of TCDD. PMID- 1897432 TI - Liver damage, voluntary alcohol intake and brain histamine. AB - Liver dysfunction induced by protocaval anastomosis (PCA) in the rat is associated with a great reduction of hepatic alcohol and aldehyde dehydrogenase activities. Despite this, PCA rats voluntarily drank more alcohol than unoperated rats. When subjected to forced alcohol consumption, shunted rats maintained their exaggerated voluntary alcohol intake whereas unoperated rats developed aversion to alcohol. Hypothalamic levels of both histamine and histidine were very high in PCA rats. When these rats were chronically exposed to alcohol, there was a slight decrease in hypothalamic histidine concentration and consequently a lower histamine content. Chronic exposure to alcohol did not, however, influence hypothalamic tissue levels of histamine or histidine in unoperated rats. In both groups, chronic alcohol treatment exerted a stimulatory effect on hepatic alcohol metabolizing enzymes. PMID- 1897434 TI - Plasma and mucosal histamine after small bowel transplantation in rats. AB - During the course of a study on preservation of small bowel transplants in rats, the hypothesis that histamine may play a role in graft damage has been investigated. Plasma and mucosal histamine levels have been measured after storage and reperfusion of Lewis rat small bowel transplants which have received an intravascular flush of saline or of one of the tissue preservation media, hypertonic citrate or University of Wisconsin solution. Plasma histamine concentration was unchanged from a control value of 23.2 +/- 2.6 ng/ml 15 min after reperfusion of grafts, whether fresh or stored for 24 h or for 48 h. Mucosal histamine levels in the grafts fell, however, from a control value of 371.0 +/- 22.9 ng/g tissue, first on storage then further after 15 min reperfusion. No differences were found in these parameters of histamine release between any of the preservation media. It is suggested that histamine may play a role in storage and reperfusion damage to small bowel transplants. PMID- 1897435 TI - Effect of pentacaine and ranitidine on gastric mucus changes induced by cold restraint stress in rats. AB - The potential involvement of increased mucus secretion in the antiulcer activity of a cytoprotective agent, pentacaine, and of the H2-antagonist ranitidine was studied in stressed rats. Cold-restraint stress decreased the gastric mucus content and induced haemorrhagic erosions in the stomach. Pretreatment with pentacaine and ranitidine dose-dependently diminished the extent of stress induced gastric damage. Pentacaine prevented the depletion of mucus after stress, while ranitidine failed to affect it. In non-stressed rats only pentacaine was able to enhance mucus secretion. The stimulating effect of pentacaine on gastric mucus secretion may account for some of its antiulcer properties. PMID- 1897436 TI - Distribution of histamine in developing rat tissues. AB - An antiserum against conjugated histamine was used to reveal the location and time of the appearance of the amine in different organs during the development of fetal and early postnatal rats. Tissues were fixed in 4% 1-ethyl-3(3-dimethyl aminopropyl) carbodiimide and standard indirect immunofluorescence technique was used. Histamine-immunoreactivity (HA-ir) was first detected in the rat fetus on the 10th embryonic day (day E10) in the embryonic liver. The liver remained immunoreactive during the second half of the fetal life. In addition to some small HA-ir cells in the stomach wall and in the kidneys on day E16, the papillary muscles of the fetal heart also exhibited patchy immunofluorescence at this stage. On day E18, HA-ir cells appeared in many other organs including lungs, gastric mucosa and smooth muscle cells of the stomach wall, heart muscle and subcutaneous tissue. The distribution of HA-ir in fetal tissues was most extensive on day E20 when the kidney tubules and the skin also exhibited bright fluorescence. These results suggest that histamine is widely distributed during fetal development in different cell types. PMID- 1897437 TI - Heterogeneity of [3H]-mepyramine binding sites in guinea pig cerebellum and lung. AB - The nature of histamine receptors in peripheral tissues is still controversial. However, evidence of heterogeneous classes of binding sites for [3H]-mepyramine are reported in the literature. The aim of our study was, therefore, to investigate the nature of this heterogeneity by comparing [3H]-mepyramine binding in a central tissue (cerebellum) and in a peripheral tissue (lung) obtained from guinea pigs and to assess its dependence upon the temperature of incubation. The results revealed that the [3H]-mepyramine interaction in both tissues is temperature-dependent. At 25 degrees C, the interaction between [3H]-mepyramine and the receptors was biphasic in the lung while only a single class of binding site was found in the cerebellum. At 0 degrees C, [3H]-mepyramine interacted with three binding sites in the lung and two in the cerebellum. The behaviour of the reference compounds (clemastine, promethazine and histamine) also supported this temperature-dependence. Moreover, two new compounds (DF 11062 and DF 11113), synthesized in our laboratories and endowed with antihistamine activity, can differentiate between the low affinity site seen at 25 degrees C in the lung and that seen in the cerebellum at 0 degrees C. PMID- 1897438 TI - Histamine in C3H/W mice carrying spontaneous tumors of the mammary gland. AB - Adenocarcinoma mammae, a spontaneously growing mammary cancer in C3H/W mice, contrary to many transplanted tumors does not evoke any rise in histamine level either in the tumor or in distant tissues. On the other hand, the histamine level is reduced by 90% in the tumor in comparison with the healthy gland. This seems to be a consequence of the fall of histidine decarboxylase activity to below a detectable level. There is also a significant reduction in histamine N methyltransferase activity to one-fifth of the control level. The healthy mammary gland contains a high concentration of histamine and catabolizes it exclusively through the methylation pathway. PMID- 1897439 TI - The effect of capsaicin application on mast cells in normal human skin. AB - Peptides released from sensory nerves during an axon reflex are thought to cause mast cell degranulation, histamine (Hi) release and Hi-induced vasodilatation leading to the flare of the triple response. Capsaicin stimulates peptide release from sensory neurones and causes flare in vivo but does not cause Hi release from mast cells in vitro. The effects of capsaicin on mast cell degranulation in human skin in vivo has been studied by histological examination of skin biopsies after topical capsicin (1%) treatment of stratum corneum-denuded forearm in four volunteers. The results show a significant reduction in the visible numbers of mast cells and the appearance of degranulated mast cells ghosts in the skin six hours after capsaicin application. Since capsaicin itself does not release Hi from mast cells, these data suggest that capsaicin-induced release of peptides from neurones could cause mast cell degranulation. PMID- 1897440 TI - Elevated plasma histamine concentration as a sensitive real-time parameter for distinct phases of surgical trauma: a tool for technology assessment. AB - High technology plays an important role in surgery, either to expand surgical procedures or to reduce tissue trauma, which is a main goal of minimum invasive surgery. Due to the tremendous increase of costs the problem of technology assessment will not only be solved by statistical methods, but also by biomedical considerations and laboratory tests. Histamine release could be an indication for tissue trauma, which is caused directly by tissue damage or indirectly by infection or hypoxia. Therefore histamine release was investigated during different phases of operation in two clinically very important and complex situations: resection of liver metastases of colorectal carcinoma and resection of the oesophagus because of an oesophageal carcinoma. To model this situation in animal experiments, two randomized controlled studies were conducted in sheep. Traditional techniques were compared with techniques of minimum invasive surgery. Plasma histamine levels were determined at well-defined phases of the operation. Histamine release was demonstrated at distinct phases of operation indicating considerable specificity of this parameter, if sensitivity is guaranteed by advanced tests. Incision of the liver capsule by thermocauterization, liver ischaemia, tissue trauma in more extended disruption of perioesophageal tissue were causes of more extended histamine release. It is concluded that measurement of plasma histamine is a suitable indicator for discriminating between extended and minimum invasive surgery. The consequence of considering this parameter may be less complications in the post-operative period and a short hospital stay with better quality of life. PMID- 1897441 TI - The effects of morphine, morphine plus scopolamine, midazolam and promethazine on cerebrospinal fluid histamine concentration and postoperative analgesic consumption. AB - The effects of morphine (0.14 mg/kg), morphine (0.14 mg/kg plus scopolamine (0.042 mg/kg), midazolam (0.015 mg/kg) and promethazine (0.08 mg/kg) on cerebrospinal fluid histamine (CSF-HA) and CSF-methylhistamine were investigated in 44 healthy patients. CSF-HA was determined by HPLC. CSF-HA was found to be increased after all premedications with great individual variation (range 0.07 7.4 pmol/ml). The highest values were found in the promethazine group (1.83 +/- 2.2 (SD) pmol/ml and the lowest in the control group (0.63 +/- 0.42 pmol/ml). Measurable concentrations of CSF-methylhistamine were found in 13 patients without correlation with HA. Postoperative need for analgesics was reduced in all premedicated groups. A significant correlation existed between HA and need for postoperative analgesics in the morphine plus scopolamine group. It is concluded that the histamine system plays a role in central nociception. PMID- 1897442 TI - Measurement of urinary N tau-methylhistamine excretion: correlation of a newly developed radioimmunoassay (RIA) with gas chromatography mass spectrometry (GCMS). AB - A newly developed radioimmunoassay (RIA, Y) for the determination of urinary N tau-methylhistamine concentrations was correlated with gas chromatography mass spectrometry (GCMS, X). In 34 urine samples, with histamine and N tau methylhistamine levels within our reference values, the correlation was: Y = 1.47X -0.245 mumol/l (r = 0.92; p-slope less than or equal to 0.0001). In 14 pathological urine samples, derived from patients with mastocytosis and having upper reference values, the correlation was: Y = 1.75X - 1.02 mumol/l (r = 0.93; p-slope less than or equal to 0.001). In spite of the greater specificity of the monoclonal antibody for N tau-methylhistamine compared with that of histamine, relatively high urinary histamine concentrations gave a false positive influence on the RIA results, which was 100% when the histamine/N tau-methylhistamine ratio was about 19. Clear cases of mastocytosis can be diagnosed, using the RIA-kit, but for a more precise N tau-methylhistamine value GCMS analyses will remain necessary. PMID- 1897443 TI - Evaluation of mast cell activation (tryptase) in two patients suffering from drug induced hypotensoid reactions. AB - Tryptase is predominantly found in mast cells, where it resides in secretory granules, and is released with other mediators during mast cell degranulation. By using a newly developed commercial assay for measurements of tryptase levels we have investigated two cases of suspected drug-induced anaphylaxis. Each patient had a similar clinical presentation, consisting of hypotension and cyanosis after administration of thiopentone and suxamethonium. One of the patients showed a highly elevated serum level of tryptase reaching 26 micrograms/l 30 min after the initial reaction. In addition, slightly elevated levels of specific IgE antibodies to thiopentone were detected. The other patient with similar symptoms showed no increase in the level of tryptase, nor any specific IgE to thiopentone or suxamethonium. These data indicate the patient I suffered from true anaphylaxis, whereas the reaction of patient II occurred by a different mechanism. PMID- 1897444 TI - The role of mast cells in redistribution of tele-methylhistamine in the body. AB - The basis of this study was the assumption that mast cells can take up tele methylhistamine (MeHi), as is known for other biogenic amines. The influence of extracellular MeHi on its uptake (active or passive) in isolated rat mast cells and in different rat tissues was studied in vitro. Rat peritoneal mast cells were incubated for 15 or 30 min at 37 or 1 degree C with different concentrations of MeHi. Submandibular gland, skeletal muscle, lung and heart of the rat (200-500 mg of each) were chopped and incubated for 20 min at 37 or 1 degrees C in buffer containing MeHi. Histamine (Hi) and MeHi in the cells and in the tissues were then determined by HPLC assay. Mast cells were capable of taking up MeHi in a time- and dose-dependent manner. MeHi levels increased from 5-10 ng per ml of incubated cell suspension (control) to 60-100 ng/ml after 15 min incubation. It can be assumed that the accumulation of MeHi in mast cells is due to a simple diffusion process since no significant change was noticed at 1 degree C. The preincubation of the cells with serotonin reduced MeHi accumulation, thus indicating MeHi competes with the same binding sites in mast cells as Hi and serotonin. Tissues showed high capacity for MeHi accumulation and MeHi surmounted endogenous Hi levels. Uptake was reduced at 1 degree C, yet the accumulation of MeHi was still high. The results indicate that mast cells can take up a smaller portion of free MeHi and they can have a function in its micro-regulation whereas other tissue cells have a predominant role in the removal of free MeHi from the blood. PMID- 1897446 TI - Role of the cytoskeleton in Ca2+ release from the intracellular Ca store of rat peritoneal mast cells. AB - In order to study the role of the cytoskeleton in histamine release from mast cells, the effects of cytochalasin D, cholchicine and vinblastine on Ca2+ release from the intracellular Ca store induced by compound 48/80 were investigated by means of a video-intensified microscopy system. When the quin 2-loaded mast cells were stimulated by 0.35 micrograms/ml of compound 48/80, a rapid increase in intracellular Ca2+ was observed. At concentrations higher than 10(-6) M, both colchicine and vinblastine pretreatments significantly inhibited the increase in intracellular Ca2+ concentrations caused by compound 48/80, although cytochalasin D had no effect. When permeabilized mast cells were exposed to potassium antimonate solution, microtubules became attached to the endoplasmic reticulum, where many dots of Ca-antimonate were observed; in some areas, the microtubules interconnected the endoplasmic reticulum and granules in the mast cells. From the results of the present study, it was assumed that microtubules play some important role in the processes leading to Ca2+ release from the intracellular Ca store. PMID- 1897445 TI - Biological effects of histamine: an overview. PMID- 1897447 TI - The existence of filaments connecting the granules and the cell membrane in rat peritoneal mast cells. AB - SEM images of rat peritoneal mast cells showed that microtubule-like filaments seemed to penetrate the granules and project several branches just beneath the granular surface. Each granule appeared to be a cluster of microgranules. TEM observations frequently revealed microtubules connecting the granule surface to the subplasmalemmal network or to the adjacent granule surface and on some occasions, microtubules also appeared to penetrate the granule membranes. Moreover, TEM revealed that individual granules seemed to consist of a mass of microgranules, each 10-15 nm in diameter; freeze-fracture images showed similar configurations. These findings suggest that the microtubule-like filamentous structures in mast cells play a role corresponding to that of the open canalicular system in platelets. PMID- 1897449 TI - Lack of specific saxitoxin binding to rat mast cells. AB - We studied whether or not mast cells are endowed with specific sodium channels, by using tritiated saxitoxin which binds to site 1 of sodium channels on excitable tissues. Our results suggest that rat pleural and peritoneal mast cells lack specific sodium channels. PMID- 1897450 TI - [Blood-aqueous barrier]. PMID- 1897448 TI - The role of the sodium pump in the plasma membrane potential changes during mast cell activation. AB - The role of the sodium pump in the plasma membrane potential changes induced by compound 48/80 and by antigenic challenge has been investigated using a fluorescent potential sensitive probe, bis-oxonol. Compound 48/80 induced a fast decrease of the fluorescence of bis-oxonol followed by a delayed decrease. The antigenic stimulation induced only a delayed decrease of fluorescence. Zinc gluconate inhibited the first decrease but did not alter the second one. The delayed decrease was inhibited by ouabain or by the absence of potassium. These results suggest that compound 48/80 induced mast cell secretion via a zinc sensitive mechanism followed by activation of the sodium pump. The changes in the plasma membrane potential during the antigenic stimulation are due to the activation of the sodium pump but occur after the secretion process. PMID- 1897451 TI - [Time course of changes in aqueous flare following intravitreous gas injection in rabbits]. AB - The quantitative changes of the aqueous flare following intravitreous gas injection were determined by laser flare-cell metry in rabbits. A volume of 0.4 ml of air, 100% sulfur hexafluoride (SF6), or 100% perfluoropropane (C3F8), was injected separately into the vitreous of pigmented rabbits. The normal range of the aqueous flare was 7.8 +/- 3.0 (photon counts/msec). Each model showed an increase of aqueous flare on the first day (air: 18.9 +/- 9.1, SF6: 19.5 +/- 11.5, C3F8: 40.8 +/- 22.8). Subsequently, the aqueous flare of air-injected eyes gradually decreased, while that of SF6-injected eyes increased on the 4th day, and then gradually decreased. Also that of C3F8-injected eyes increased on the 4th day, and the 7th day, then decreased on the 14th day, but it was still higher than normal. Cataracts developed in two of the five eyes injected with SF6 and all of the four eyes injected with C3F8. These findings revealed that following intravitreous gas injection, disruption of the blood-ocular barrier depended on the expansibility of the gas and the length of time it remained in the vitreous cavity. PMID- 1897452 TI - [Changes in ocular structure and in blood-ocular barrier permeability of experimental myopia induced in monkeys]. AB - We induced myopia by eyelid suturing in one eye each of six 9-month-old cynomolgus monkeys to elucidate the condition by studying changes in the ocular structure and the blood-ocular barrier (BOB) permeability. Optical elements were measured by A-mode ultrasonography; vitreous fluorophotometry was carried out to document BOB permeability before eyelid suturing and 3, 10, 16, and 28 months after suturing. The axial length of the sutured eyes increased significantly compared with that of the non-sutured contralateral eyes at 10 months after suturing and continued to lengthen with time. The dioptric power (D) of the sutured eyes changed in the same way. (mean, -3.08D 28 months after suturing). The permeability of the blood-retinal barrier of the sutured eyes significantly increased from 10 months after suturing compared with that of the fellow eyes, and continued to increase over the period of observation. The permeability index of the blood-aqueous barrier also increased significantly from only 16 months after suturing further increasing as the period of observation lengthened. We hypothesize that in the transition from emmetropia to myopia, the permeability of the BOB rises, and continue to rise as myopia develops. Thus, the breakdown of the BOB, i.e., the breakdown of the ocular homeostasis, is considered to be closely related to the occurrence and the development of myopia. PMID- 1897453 TI - [The influence of aging on the development of rat galactosemic cataract]. AB - In order to investigate the effect of age on the rat galactosemic cataract, 3, 6, 12 and 24-week-old rats were fed with a 50% galactose diet. The cataractous lenses were observed by light microscopy, and the amount of galactitol measured. All rats fed with 50% galactose developed cataracts in the equatorial region. However, the morphological and biochemical development of the galactose cataract in old rats was slower than in young rats. These results suggested that older diabetic patients are less likely to develop diabetic cataract than younger patients. PMID- 1897454 TI - [Comparison of shape recovery ratios in various IOL haptics]. AB - We examined shape recovery ratios of various IOL haptics (polypropylene, polyvinylidene fluoride, polymethylmethacrylate) under conditions resembling clinical use. Experiments were carried out using Ascon lens-holding forceps and compression tests in cylindrical holders. The experimental results indicated that PVDF haptics were superior to PP and 3-piece PMMA haptics. This would suggest the need for surgeons to establish safer implantation techniques in the future by taking into consideration the shape recovery characteristics of the haptics involved. At the same time, further research and development of haptic materials is required by manufacturers. PMID- 1897455 TI - [Effects of extracellular K+ concentration on the ERG c-wave]. AB - The effects of K+ concentration in the perfusate on ERG were examined in bullfrog neural retina-retinal pigment epithelium-choroid preparations. In the range of K+ concentration between 1.0 and 6.0 mM, an increase in K+ concentration caused a decline in the b-wave amplitude, while leaving the b-wave peak latency almost unchanged. An increase in K+ concentration in the range between 1.0 and 3.0 mM enhanced the c-wave amplitude, while an increase in K+ concentration in the range between 4.0 and 6.0 mM diminished it. An increase in K+ concentration tended to shorten the time course of the c-wave. These results suggest that variations in the K+ concentration in tissue fluid may partially account for the marked inter- and intra-individual variations of the c-wave. PMID- 1897456 TI - [The influence of the light stimulus on VIP mRNA in VIP containing neurons of the rat suprachiasmatic nucleus]. AB - In this study, an in situ hybridization technique combined with computed image analysis was performed to examine whether or not synthesis of vasoactive intestinal peptide (VIP) was influenced by a light stimulus from the retina and diurnal changes of messenger RNA (mRNA) of VIP in the rat suprachiasmatic nucleus (SCN) were measured. The amount of mRNA was largest at 2:00 am, second largest at 20:00 pm during the dark phase and smallest at 14:00 pm during the light phase. We also confirmed the onset of fluctuation of mRNA preceding the diurnal variation of the content of the VIP-like immunoreactivity established by semiquantitative immunocytochemistry and this fluctuation was abolished under constant dark conditions. The present finding strongly suggested that light stimulus from the retina primarily influenced the transcription of VIP mRNA and induced diurnal variation of VIP synthesis. PMID- 1897457 TI - [The effect of viscoelastic substances on postsurgical blood aqueous barrier]. AB - A postsurgical flare was evaluated with a flare-cell meter and the effect of residual viscoelastic substances on the blood aqueous barrier function was studied. The materials consisted of 100 eyes undergoing extracapsular cataract extraction and posterior chamber lens implantation using sodium hyaluronate products (Healon:Pharmacia and Opegan:Santen). The molecular weight is 1.9-3.6 million daltons in Healon and 0.9-1.2 million daltons in Opegan. According to the aqueous warm current on the 1st postoperative day, the eyes were divided into two groups; the poor current group and the normal current group. The poor current group consisted of 13 eyes had static aqueous current, probably due to residual viscoelastic substances from the clinical findings, namely a little pain, foggy general corneal edema and spontaneous recovery of the warm current without specific administrations of antibiotics. Eyes with poor current were recognized in 18% (11/62) among cases with Healon and 5% (2/38) in case with Opegan. Flare values of the poor current group were higher in 7 eyes than the highest of the normal current group on the 1st postoperative day. After the 2nd postoperative day, the median flare value of the poor current group was higher than that of the normal current group. The difference was statistically significant throughout the first week (p less than 0.02). The cell number was also higher in the poor current group on the 1st and 2nd postoperative day (p less than 0.02). These findings suggest that the residual viscoelastic materials may increase the breakdown of blood-aqueous barrier and/or interfere the barrier recovery. PMID- 1897458 TI - [The biochemical study in the nucleus opacification of the senile cataractous lens]. AB - The lens nucleus has various colors, sizes and hardness. It is of significance to investigate the components of the nucleus and the factors participating in the mechanism of development of cataract. Recently, the author demonstrated that free lipid in cataract does not undergo quantitative change, compared with that in the normal lens but that the cholesterol and phospholipid in the nucleus and cortex increase in the urea-soluble protein fraction. An assay of lipid-protein complex (lipoprotein) was made and also quantitative changes were studied using nucleus with different colors in senile cataract. The study was made by the technique developed by the author because no other experimental procedure has been established for lipoprotein in the tissue. Chylomicron, VLDL, LDL and HDL were identified in lipoprotein. The amount of lipoprotein decreased as the color of the nucleus became dense, but only HDL among these increased. The catabolism of lipoprotein advanced when the color of nucleus changed from light yellow to brown, suggesting that disorder in mass transfer is caused. PMID- 1897459 TI - [Tissue culture of human lens epithelial cells. Part II: Suppressive effect of diclofenac sodium on their proliferation and metaplasia]. AB - We studied the suppressive effect of a non-steroidal anti-inflammatory drug (NSAID) on the proliferation and fibrous metaplasia of human lens epithelial cells (LEC) in cell culture. We cultured human LEC attached to a round piece of the central anterior capsule obtained by anterior capsulotomy during cataract surgery and added diclofenac sodium, the concentration of which varied from 0.5 microgram/ml to 30 micrograms/ml gradually. Proliferation as well as fibrous metaplasia of LEC were suppressed. Histopathological examination revealed cell degeneration and death. Besides the apparent inhibition of diclofenac sodium on the biosynthesis of prostaglandins, this suppressive effect on LEC proliferation also may play a role in anti-inflammation after intraocular lens implantation. Further, secondary cataract may be prevented by this effect. PMID- 1897460 TI - [Localization of glutathione-S-transferase in transparent and cataractous human lenses]. AB - The localization of glutathione-S-transferase (GST) activity was investigated in 15 cataractous lenses obtained by intracapsular extraction of senile cataract. Additionally, 8 clear lenses, obtained from donor eyes in cases of corneal transplantation or of traumatic lens luxation, were used as controls. The lenses were divided into the central and peripheral portions with a trephine. The activity of GST was quantitated in each portion according to the method described by Habig. GST activity in clear lenses was significantly higher in the peripheral portion than in the central portion and in the former it was significantly higher in clear lenses than in cataractous ones. The ratio of GST activity between central and peripheral portions (C/P) was significantly higher in cataractous lenses than in clear ones. These findings suggested that the scavenging system of the human clear lens is more active in the equatorial portion than in the central portion. Nevertheless the activity of GST in human cataractous lenses decreased more significantly in the peripheral portion than in the central portion. These findings indicated that the human cataract usually develop from equatorial portion of lens. PMID- 1897461 TI - [Effect of photocoagulation on retinal mean circulation time in proliferative diabetic retinopathy by use of fluorescein video angiography and image analysis system]. AB - The effect of panretinal photocoagulation (PRP) on mean circulation time (MCT) was investigated in a main nasal superior artery and vein of 13 eyes with proliferative diabetic retinopathy, using fluorescein video angiography and an image analysis system. MCT before photocoagulation averaged 5.67 +/- 1.40 seconds. Two weeks after PRP, MCT averaged 4.29 +/- 0.89 sec., one month after, 4.29 +/- 0.88 sec., three months after, 4.03 +/- 0.86 sec., and six months after, 3.61 +/- 0.31 sec. The MCTs after PRP were shorter than MCT before PRP (p less than 0.01). These results suggest that MCTs in proliferative diabetic retinopathy shortened soon after PRP. PMID- 1897462 TI - HCFA blinks. PMID- 1897464 TI - Futures in your future. PMID- 1897463 TI - Congestive heart failure. PMID- 1897465 TI - A teenager looks at malpractice. PMID- 1897466 TI - The 60s Medicare debate revisited. PMID- 1897467 TI - Educating physicians in nutrition--a view of the past, the present, and the future. PMID- 1897469 TI - Human resting energy expenditure in relation to dietary potassium. AB - This study investigates the putative effect of potassium on energy expenditure. Eight young adult men were submitted to two different normocaloric mixed diets in a randomized order, containing either 163 +/- 9 or 69 +/- 2 mmol potassium/d. On the fifth day of each diet, after an overnight fast, resting metabolic rate (RMR) was measured over a 1-h period. After these measurements, either a potassium load (50 mmol) or a placebo were given to subjects submitted to the low- or the high potassium diet, respectively. RMR was then measured again for 3 h and the last hour was kept for further analysis. Results showed that acute and chronic variations in potassium intake do not induce significant changes in RMR, and chronic but not acute changes in serum potassium concentration were significantly correlated with changes in energy expenditure (r = 0.74, P less than 0.05) by mechanisms that remain to be elucidated. PMID- 1897468 TI - Magnetic-resonance imaging used for determining fat distribution in obesity and diabetes. AB - Computed-tomography scanning and magnetic-resonance imaging (MRI) have been used to quantify intraabdominal and subcutaneous fat depots. In this study MRI was used to define fat-distribution patterns in 24 obese females with non-insulin dependent diabetes (NIDDM) and 12 females with simple obesity. Subjects had anthropometric measurements and single-slice abdominal scans performed at the umbilicus. In addition, in 10 of the nondiabetic females, measurements were repeated after 10 wk of a very-low-calorie diet. Nondiabetic females had significantly less intraabdominal fat (P less than 0.01) than did the diabetics but had equivalent subcutaneous fat. There was no significant relationship between waist-to-hip ratio and intraabdominal fat, subcutaneous fat, or their ratio. After a weight loss of 10.6 +/- 3.8 kg there were significant decreases in both intraabdominal and subcutaneous fat (P less than 0.01). Weight loss is associated with decreases in fat in both depots. PMID- 1897470 TI - Taste preferences in human obesity: environmental and familial factors. AB - Taste-response profiles influence food selection and may help distinguish among potential subgroups of obese individuals. A representative community-based sample of 61 obese and 31 lean adults tasted five sucrose solutions and nine fat containing solid stimuli resembling cake icings. Solid stimuli contained 15-35% fat and 20-70% sucrose (by weight). No significant differences in taste responsiveness were observed between obese and lean groups. Obese subjects were then divided into subgroups based on age at onset of obesity and past fluctuations in body weight. Obese subjects characterized by large weight fluctuations showed elevated preferences for sugar and fat mixtures compared with the stable subgroup. In contrast, early age at onset of obesity (less than 10 y), thought to be a measure of familial risk, had no significant effects on taste preferences. Environmental as opposed to familial factors may be more immediate determinants of taste preferences and food choice. PMID- 1897471 TI - Nutritional supplementation, psychosocial stimulation, and growth of stunted children: the Jamaican study. AB - The benefits of nutritional supplementation, with or without psychosocial stimulation, on the growth of stunted children were evaluated. Children aged 9-24 mo with lengths less than -2 SD of the National Center for Health Statistics references (n = 129) were randomly assigned to four groups: control, nutritional supplementation, stimulation, and both interventions. A fifth group with lengths greater than -1 SD was also enrolled. Length, weight, head and arm circumferences, and triceps and subscapular skinfold thicknesses were measured on enrollment and 6 and 12 mo later. Multiple-regression analysis was used to determine the effects of the interventions in which age, sex, initial status, initial dietary intake, and several socioeconomic variables were controlled for. Stimulation had no effect on growth and there was no interaction between the interventions. After 12 mo supplemented children had significantly increased length, weight, and head circumference (all P less than 0.01). The effects of supplementation were not cumulative but occurred in the first 6 mo. PMID- 1897473 TI - Determinants of pregnancy outcome and newborn behavior of a semirural Egyptian population. AB - Several potential determinants of birth weight and neonatal behavioral organization, ie, maternal anthropometry, food intake (energy, protein, and plant and animal-source foods), morbidity, and household socioeconomic status, were followed systematically in a semirural Egyptian population during greater than or equal to 6 mo of pregnancy. In early pregnancy mothers were generally normal weight to moderately overweight. Their mean energy intake, largely from plant sources, was approximately 8.37 MJ/d (2000 kcal/d) during trimesters 2 and 3. Early (3 mo) pregnancy weight and weight gain during trimesters 2 and 3 were significantly positively related to birth weight Z scores. The best predictor model examined for birth weight included early pregnancy weight, weight gain, and length of gestation (R2 = 0.45). Early pregnancy weight and maternal intake of animal-source foods were significant positive predictors of the newborn's orientation and habituation behavior, respectively. Habituation and orientation measures assess the infant's early ability to process information. PMID- 1897472 TI - A prospective cohort study of nutrient intake and age at menarche. AB - A cohort of 213 girls (aged 10 y, range +/- 9 mo) whose parents reported their dietary intakes (including nutritional supplements) using a semiquantitative food frequency questionnaire, was followed for 4 y until 82% of the 194 parents who responded to follow-up letters had reported that their daughters had had their first menstrual periods. The relative risk (RR) of menarche before age 12.5 y was 2.0 [95% confidence interval (CI) = 1.1-3.8] for the tallest girls (greater than 150 cm) compared with the shortest girls (less than 130 cm). The RR was 2.1 (95% CI = 1.1-3.8) for the fattest girls [Quetelet's index of relative weight (in kg/m2) greater than 19] vs the leanest girls (less than 15). After adjusting for height and Quetelet's index, menarcheal age was not associated with intake of energy nor energy-adjusted intake of protein, fat, or carbohydrate. The overall results are consistent with the hypothesis that nutritional factors influence age at menarche mainly through their effects on accumulation of adipose tissue. PMID- 1897474 TI - Peroxisomes and the fatty liver of malnutrition: an hypothesis. AB - Peroxisomes play a role in hepatic beta-oxidation of fat, a process that results in the production of hydrogen peroxide. The fatty infiltration of the liver that occurs in severely malnourished children remains unexplained. We observed an almost total absence of peroxisomes in the hepatocytes of these children. We suggest that lack of available peroxisomes could contribute to the development of fatty liver. PMID- 1897475 TI - Eggs enriched in omega-3 fatty acids and alterations in lipid concentrations in plasma and lipoproteins and in blood pressure. AB - Effects of dietary eggs enriched with omega-3 fatty acids on lipid concentrations in plasma and lipoproteins and blood pressure were determined in 11 men and women in two groups. Group 1 consumed four omega-3 eggs per day during the first 4-wk period and four control eggs for the second 4-wk period. Group 2 ate the same number of eggs in the reverse order. Mean plasma cholesterol concentration was significantly increased by control eggs (P less than 0.01) but unchanged by omega 3 eggs. Mean plasma triglyceride concentration was decreased by omega-3 eggs but increased by control eggs. Both systolic and diastolic blood pressures were significantly lowered by omega-3 eggs in group 1 whereas only systolic pressure was significantly decreased on omega-3 eggs in group 2. The control eggs did not change blood pressure. In conclusion, the omega-3 eggs may be more healthful than the control eggs. PMID- 1897476 TI - Feasibility of using an oleate-rich diet to reduce the susceptibility of low density lipoprotein to oxidative modification in humans. AB - Oxidized low-density lipoprotein (LDL) is more atherogenic than native LDL. The initial step in the oxidation is the peroxidation of polyunsaturated fatty acids. Thus, decreasing the concentration of polyunsaturated fatty acids should reduce the susceptibility of LDL to oxidation. Therefore, we tested the possibility that diets enriched in oleate might result in LDL that is less susceptible to oxidative modification. LDL isolated from subjects consuming an oleate-enriched diet, compared with LDL from subjects on a linoleate-enriched diet, contained significantly more oleate (28.7% vs 11.5%) and less linoleate (31.9% vs 50.9%). Generation of conjugated dienes was significantly lower in the LDL from the oleate group. Most important, after incubation with endothelial cells, LDL from the oleate group underwent less degradation by macrophages. These studies demonstrate the feasibility of altering the diet in a way that will not raise LDL cholesterol concentrations and yet will decrease the susceptibility of LDL to oxidative modification. PMID- 1897477 TI - Serum vitamin A distribution curve for children aged 2-6 y known to have adequate vitamin A status: a reference population. AB - Serum vitamin A was determined before and 30-45 d after the administration of 60.6 mg (212 mumol) vitamin A to 544 Brazilian children residing in slum areas of Recife. The frequency-distribution curves were compared in a subgroup of children whose vitamin A status was assessed initially by the relative-dose-response (RDR) test. The curves of children with negative (adequate status) and positive (inadequate status) RDR tests were different. The difference disappeared after supplementation. The shape of the distribution curve after supplementation was close to normal with a mean, median, and 95% confidence interval of 1.78 +/- 0.49, 1.68, and 1.02-2.90 mumol/L, respectively. The postsupplementation curve derived from this underprivileged child population may serve as a reference for diagnostic, surveillance, and program-evaluation purposes. PMID- 1897478 TI - Ascorbic acid and dehydroascorbic acid measurements in human plasma and serum. AB - We investigated whether circulating ascorbic acid in humans is protein bound or free and whether ascorbic acid exists in its reduced form alone as ascorbic acid or in its reduced and oxidized forms as ascorbic acid and dehydroascorbic acid, respectively. Ascorbic acid and dehydroascorbic acid were determined by using HPLC with coulometric electrochemical detection, and protein binding was determined by centrifugal ultrafiltration. Ascorbic acid was free in plasma and serum of normal, healthy volunteers, 10 men and 10 women. Ascorbic acid was detectable only in its reduced form. However, dehydroascorbic acid could be made to appear in samples processed under oxidizing conditions. Because circulating ascorbic acid is free and is detected only as reduced vitamin, ascorbic acid may be available without intermediates for peripheral utilization. Dehydroascorbic acid may not be present in plasma and serum of normal humans unless assay conditions permit ascorbic acid oxidation. PMID- 1897479 TI - Assessment of the role of nonheme-iron availability in iron balance. AB - To assess the nutritional relevance of absorption studies that use extrinsically labeled single meals, we developed a method for measuring nonheme-iron absorption from the diet and compared the results with absorption from single meals. When subjects consumed their usual diet, there was good agreement between dietary absorption (6.4%) and representative single meals fed in the laboratory (6.1%). Nonheme-iron availability, as estimated by a model that incorporated the effect of both enhancers and inhibitors, correlated significantly with absorption from single meals but not with dietary absorption. When the diet was modified to promote iron absorption maximally, dietary absorption increased only slightly (8.0%) and remained significantly lower than it was from single meals (13.5%). With an inhibitory diet, the decrease in absorption from single meals was similarly exaggerated. These results indicate that in the context of a varied Western diet, nonheme-iron bioavailability is less important than absorption studies with single meals would suggest. PMID- 1897480 TI - Day-to-day variation in iron-status indices in healthy men and women. AB - We evaluated the day-to-day variation of four iron-status indices: hemoglobin (Hb), hematocrit (Hct), plasma ferritin (PF), and plasma iron (PI). Finger-prick blood samples were collected for 31 consecutive days in 20 healthy men and women. Replicate (sigma 2rep) and day-to-day (sigma 2day) variance components were estimated. Day-to-day variation in the iron-status measures was similar between men and women except for PF, for which the variation was greater in women. The CVs for a single future determination for Hb, Hct, PF, and PI were 4.6%, 3.0%, 15.2%, and 26.7% for males and 4.4%, 3.2%, 26.8%, and 29.0% for females, respectively. Three to 10 independent measurements are required to accurately determine PF and PI whereas one is adequate for Hb and Hct. Thus, day-to-day biological variation is a major component of the variability in these iron-status indicators and must be considered when assessing iron status. PMID- 1897481 TI - Dietary risk factors associated with acute and persistent diarrhea in children in Karachi, Pakistan. AB - Feeding practices may have an important impact on diarrheal diseases in developing countries. This study evaluated feeding practices in three groups of male children aged 6-36 mo: 100 with persistent diarrhea (PD), 79 with acute diarrhea (AD), and 86 in a comparison group (CG). The children came from comparably poor socioeconomic settings in Karachi, Pakistan, except that the literacy rates were higher in mothers of the CG (P = 0.0001). Although greater than 95% of all infants were breast-fed, delayed initiation of breast-feeding was more common in the diarrhea groups. Children with diarrhea were also more likely to receive supplemental milk (PD = 92%, AD = 87%) than were children in the CG (69%, P less than 0.05). Feedings were not withheld during diarrhea but changes were made in the nature of foods given. These results indicate that several feeding practices may be important risk factors for diarrhea in Pakistan. PMID- 1897483 TI - The term alpha-tocopherol should not be used without clarification. PMID- 1897482 TI - Characteristics of vitamin and mineral supplement products in the United States. AB - A 1986 nationwide survey of 11,775 adults 18 y or older and 1877 children 2-6 y old identified approximately 3400 different (unique) vitamin and mineral supplement products being taken. The most commonly included nutrient listed on the product labels was vitamin C, which was present in 50% of the unique products examined. Calcium and iron were the most commonly included minerals and were present in 25% of the unique products examined. Prenatal and children's chewable products came in a relatively narrow potency range and generally contained nutrients in amounts approximating or less than the US recommended daily allowances. These products also contained significant minimum amounts of nutrients. Potencies of products not targeted for use by these special groups, particularly those products that were self-prescribed, varied widely and ranged from insignificant to extremely large amounts of nutrients. Units used to declare product potency or to prescribe the dosage varied. PMID- 1897484 TI - Pteroylglutamates in human milk. PMID- 1897485 TI - Phytate's potential role in reducing colon-cancer risk. PMID- 1897486 TI - Tryptophan content of Isocal. PMID- 1897488 TI - Effects of a senso (toad venom) containing drug on systemic hemodynamics, cardiac function and myocardial oxygen consumption in anesthetized dogs. AB - Effects of a Senso (toad venom)-containing drug, KY, on cardiovascular system were examined in anesthetized open-chest dogs. KY increased aortic pressure, peak positive first derivative of left ventricular pressure, stroke work index, percent segment shortening in left ventricular myocardium and myocardial oxygen consumption, and decreased heart rate and total peripheral vascular resistance (TPR). Propranolol augmented the increase in aortic pressure with KY, inhibited the increase in aortic flow with KY and reversed KY-induced decrease in TPR to an increase. These results indicate that KY has positive inotropic and vasodilating actions possibly originating from both digitalis- and adrenaline-like action of a Senso. PMID- 1897487 TI - Tryptophan content of TwoCal HN. PMID- 1897489 TI - The pharmacological and pathological studies on Taiwan folk medicine (VI): The effects of Elephantopus scaber subsp. oblanceolata, E. mollis and Pseudoelephantopus spicatus. AB - The liver protective effect of Elephantopus scaber subsp. oblanceolata, E. mollis and Pseudoelephantopus spicatus on CCL4 induced hepatotoxicity has been determined by liver enzyme functional test and pathological studies. As the result indicated, the acute increase of serum transaminase (SGOT and SGPT level which was caused by CCL4 administration (3.0ml/kg, s.c.) can be significantly reduced when treating with E. scaber subsp. oblanceolata (p less than 0.001), E. mollis (p less than 0.01), P. spicatus (p less than 0.01). The hepatic fatty metamorphosis and necrosis of central lobule were obviously improved by treating with E. scaber subsp. oblanceolata and E. mollis, while treated with P. spicatus demonstrated only a moderate protective effect. All pharmacological and pathological effects of these three crude drugs were compared with Bupleurum chinense which has been reported previously as a treatment criteria. PMID- 1897490 TI - Cucurbitacin contents in Hemsleya dolichocarpa. AB - Hemsleya dolichocarpa was studied for its cucurbitacin contents during growing period. A colorimetric method was used to determine the total cucurbitacin levels, and a TLC densitometric assay was employed for estimating dihydrocucurbitacin F and its acetate, two active principles in Hemsleya plants. Cucurbitacin contents rise progressively from May to November; the month of November is thus the most desirable time for harvesting plant materials for medicinal uses. It was noticed that the spoiled plant samples gave an intense color reaction while dihydrocucurbitacin F and its acetate levels were not significantly altered. The accuracy of the assays is discussed. PMID- 1897491 TI - Effects of herbal components of tokishakuyakusan on progesterone secretion by corpus luteum in vitro. AB - Twenty-seven-day old female rats received 20 IU PMS and 56 hours later, 40 IU hCG. Seven days after hCG treatment, the resected ovaries were incubated in vitro with herbal components of Tokishakuyakusan (TS). Mixture of hoelen + peony root + alisma rhizone + Japanese angelica root or hoelen + Japanese angelica root or Japanese angelica root + cnidium rhizome significantly increased progesterone secretion, and these levels tended to exceed the level by TS alone. These results suggest an exquisitely blended effect of herbal components of TS on progesterone secretion by corpora lutea. PMID- 1897492 TI - Blended effects of herbal components of tokishakuyakusan on somatomedin C/insulin like growth factor 1 level in rat corpus luteum. AB - The effect of herbal components of Tokishakuyakusan on somatomedin C/insulin-like growth factor I (IGF-1) level in medium from rat corpora lutea incubated in vitro was examined. Hoelen + poeny root + Japanese angelica root, hoelen + peony root, hoelen + Japanese angelica root or peony root + Japanese angelica root decreased the IGF-1 level. The data suggest that constituent herbal components of Tokishakuyakusan regulate the IGF-1 level by rat corpora lutea. PMID- 1897493 TI - Effects of hachimijiogan, tokishakuyakusan, keishibukuryogan, ninjinto and unkeito on estrogen and progesterone secretion in preovulatory follicles incubated in vitro. AB - Ovarian follicles, removed from 10-week old rats at 1630 hours diestrus-2, 1100 and 2300 hours proestrus, were incubated for 120 minutes with various doses of Hachimijiogan (HJ), Tokishakuyakusan (TS), Keishibukuryogan (KB), Ninjinto (NT) and Unkeito (UT). The estradiol-17 beta (E2) and progesterone concentrations in the incubation medium were measured. The concentrations of E2 were significantly decreased with TS and KB by growing follicles and with HJ, TS and KB by preovulatory follicles before a LH surge. In contrast, the levels of progesterone were significantly increased with HJ, TS, KB and UT by preovulatory follicles before a LH surge. These results suggest that HJ, TS, KB or UT stimulates preovulatory follicles before a LH surge to secrete progesterone, but TS or KB suppresses E2 secretion by growing preovulatory follicles before a LH surge. PMID- 1897495 TI - The medical aphorisms of Muhammad the Prophet of Islam: a translation. PMID- 1897494 TI - Effect of paeoniflorin, glycyrrhizin and glycyrrhetic acid on ovarian androgen production. AB - We have shown that traditional herbal medicine, Shakuyaku-Kanzo-To consisted of Shakuyaku and Kanzo decreased serum testosterone levels in woman and rat. Therefore, paeoniflorin and glycyrrhizin, a main component of Shakuyaku and Kanzo, respectively, and glycyrrhetic acid, a metabolite of glycyrrhizin in vivo, were investigated for the steroid production in the rat ovary on the morning of proestrus. The homogenized tissues of one ovary were incubated in the Dulbecco's modified Eagle medium (pH 7.5) with 100 micrograms/ml of paeoniflorin, glycyrrhetic acid and glycyrrhizin and the medium only (the control) at 37 degrees C for 270 min. After the centrifugation, the concentrations of delta 4 androstenedione, testosterone and estradiol in the supernatants were determined by RIA. The production of the hormones expressed by [concentration x supernatant volume/weight of the ovary] was compared to the control. Paeoniflorin, glycyrrhetic acid and glycyrrhizin decreased significantly the testosterone production but did not change that of delta 4-androstenedione and estradiol. Testosterone/delta 4-androstenedione production ratio was lowered significantly by paeoniflorin, glycyrrhetic acid and glycyrrhizin. Estradiol/testosterone production ratio was increased significantly by glycyrrhetic acid and not changed by paeoniflorin and glycyrrhizin. These results suggest that paeoniflorin, glycyrrhetic acid and glycyrrhizin affect the conversion between delta 4 androstenedione and testosterone to inhibit testosterone synthesis and stimulate the aromatase activity to promote estradiol synthesis by the direct action on the rat proestrous ovary. PMID- 1897496 TI - WHO and the development of acupuncture nomenclature: overcoming a Tower of Babel. AB - At present, WHO does not have an official policy on acupuncture. The Organization's policies are usually developed after a debate has taken place on a particular health issue. There has not yet been a debate on acupuncture. This paper reviews WHO's efforts to produce a standard acupuncture nomenclature as a first step towards ensuring that a debate on acupuncture takes place in an atmosphere of greater understanding of the contribution that acupuncture can make in the delivery of health care. Activities that the programme for traditional medicine hopes to implement in the coming years are outlined. PMID- 1897497 TI - Treatment of iatrogenic Cushing's syndrome in dogs with electroacupuncture stimulation of stomach 36. AB - This study was conducted to evaluate the effectiveness of electroacupuncture (EA) on the recovery of adrenocortical function from Iatrogenic Cushings Syndrome (ICS) in dogs. Experiment I: Selection of the most effective Acupuncture point to treat ICS--Six healthy adult female dogs were treated bilaterally with EA for 15 minutes at loci BL22 + BL23 + BL24, ST36, or a non-locus control point on M. brachialis. Each dog was tested at all three sites in rotation. Blood samples were collected before and 0, 15 and 60 minutes after EA, and the serum cortisol levels were measured by radioimmunoassay. The data showed that EA at ST36 resulted in the highest response of serum cortisol levels among the three treatments. Experiment II: Evaluation of the effectiveness of EA ST36 in the treatment of ICS in dogs--Eight healthy adult female dogs were given prednisolone acetate 2mg/kg/day IM for 3 weeks. They were then randomly divided into ST36 and control groups of 4 dogs each. In the ST36 group, ST36 was treated bilaterally with EA for 30 minutes, 3 times per week, for 3 consecutive weeks. For the control, a non-locus point on M. brachialis was treated bilaterally with the same protocol. After the first week of EA, the serum cortisol levels of the ST36 and control groups were 0.9 +/- 0.1 and 0.5 +/- 0.1 micrograms/dl (P less than 0.005) baseline and 2.5 +/- 0.2 and 1.4 +/- 0.4 micrograms/dl (p less than 0.05) and after ACTH stimulation test, respectively. After the third week of EA treatment, the results were 1.0 +/- 0.1 and 0.6 +/- 0.2 micrograms/dl (p less than 0.05) baseline and 4.0 +/- 0.5 and 1.7 +/- 0.5 micrograms/dl (p less than 0.001) after ACTH stimulation respectively. These data indicated that EA at ST36 could restore the adrenocortical hypofunction resulting from ICS in dogs. PMID- 1897498 TI - Were we really wrong? PMID- 1897500 TI - Commentary: re: "A case-control study of milk drinking and ovarian cancer risk". PMID- 1897499 TI - The influence of lactose consumption on the association of oral contraceptive use and ovarian cancer risk. AB - The authors investigated the joint effects of diet and oral contraceptive use on ovarian cancer risk in 194 white women aged 65 years or less with epithelial ovarian cancer and 193 age- and residence-matched controls in Boston between 1984 and 1987 by using in-person interviews and self-administered food frequency questionnaires. Use of oral contraceptives for 3 months or more was associated with a modest protective effect for ovarian cancer (odds ratio (OR) = 0.7, 95 percent confidence interval (CI) 0.5-1.1). In women who consumed 11 g or less per day of lactose, use of oral contraceptives for 3 months or more was associated with a nonsignificant increased risk (OR = 1.6, 95 percent CI 0.8-3.2). In women who consumed more than 11 g per day of lactose, use of oral contraceptives for 3 months or more was associated with a substantially decreased risk of ovarian cancer (OR = 0.3, 95 percent CI 0.1-0.7). Within this group, the strongest association occurred with more than 4 years of total oral contraceptive use (OR = 0.2, 95 percent CI 0.1-0.6) and in those who had more than 2 years of oral contraceptive use after age 30 years (OR = 0.1, 95 percent CI 0.03-0.4). These results suggest that, with respect to ovarian cancer, lactose users may be the most likely to benefit from oral contraceptive use and that the benefit may be strongest when oral contraceptive use occurs after age 30 years. PMID- 1897502 TI - Melanoma and the sun: the effect of swimsuits and a "healthy" tan on the risk of nonfamilial malignant melanoma in women. AB - The authors examined the relation between sun exposure and melanoma risk and tested the previously published site-specific association of bikini use and melanoma of the trunk in a study of 130 cases incident between 1976 and 1984 and 300 controls nested within the Nurses' Health Study. A summary variable derived from four measures of sun sensitivity was more closely associated with melanoma than any component measure. There was no association of bikini use at ages 15-20 years with trunk melanoma risk (relative risk (RR) = 0.8, p = 0.7), and the 95% confidence interval (CI) (0.3-2.6) excludes the previously published estimate. High frequency of swimsuit use outdoors at ages 15-20 years was associated with increased melanoma risk among sun-sensitive women (RR = 6.4, 95% CI 1.7-23.8, p = 0.006), but appeared to be protective among sun-resistant women (RR = 0.3, 95% CI 0.1-1.0, p = 0.06). These findings suggest that the risk of trunk melanoma associated with bikini use is at most modest and that sun-sensitive women may increase their risk of melanoma with frequent sun exposures, but that sun resistant women do not, presumably because they develop a photoprotective tan. PMID- 1897501 TI - Invited commentary: progress in the nutritional epidemiology of ovary cancer. PMID- 1897503 TI - Dietary antioxidants and the risk of lung cancer. AB - The relation between the intake of retinoids, carotenoids, vitamin E, vitamin C, and selenium and the subsequent risk of lung cancer was studied among 4,538 initially cancer-free Finnish men aged 20-69 years. During a follow-up of 20 years beginning in 1966-1972, 117 lung cancer cases were diagnosed. Inverse gradients were observed between the intake of carotenoids, vitamin E, and vitamin C and the incidence of lung cancer among nonsmokers, for whom the age-adjusted relative risks of lung cancer in the lowest tertile of intake compared with that in the highest tertile were 2.5 (p value for trend = 0.04), 3.1 (p = 0.12), and 3.1 (p less than 0.01) for the three intakes, respectively. Adjustment for various potential confounding factors did not materially alter the results, and the associations did not seem to be due to preclinical cancer. In the total cohort, there was an inverse association between intake of margarine and fruits and risk of lung cancer. The relative risk of lung cancer for the lowest compared with the highest tertile of margarine intake was 4.0 (p less than 0.001), and that for fruits was 1.8 (p = 0.01). These associations persisted after adjustment for the micronutrient intakes and were stronger among nonsmokers. The results suggest that carotenoids, vitamin E, and vitamin C may be protective against lung cancer among nonsmokers. Food sources rich in these micronutrients may also have other constituents with independent protective effects against lung cancer. PMID- 1897504 TI - Geographic and birth cohort associations of Kaposi's sarcoma among homosexual men in Canada. AB - The authors conducted an analysis of all 677 cases of Kaposi's sarcoma among the 3,047 cases of acquired immunodeficiency syndrome diagnosed in homosexual/bisexual men in Canada between 1980 and 1989. The proportion with Kaposi's sarcoma declined from 32.2% during 1980-1985 to 15.0% in 1989. The proportion with Kaposi's sarcoma was significantly higher in primary epidemic centers (Vancouver, Toronto, and Montreal) and in men in the 1945-1954 birth cohort independent of year of diagnosis. These data are consistent with an environmental cofactor for Kaposi's sarcoma which is likely to be a sexually transmitted agent. PMID- 1897505 TI - Blood pressure and mortality risk in the elderly. AB - Blood pressure was assessed between 1981 and 1983 in all persons over age 65 years in three communities (East Boston, Massachusetts; New Haven, Connecticut; and Iowa and Washington countries, Iowa), and cause-specific mortality was monitored annually over the subsequent 5 years as part of the National Institute on Aging-sponsored Established Populations for Epidemiologic Studies of the Elderly. Each community had 80% or more participation: in East Boston, 3,809 persons with 903 deaths, in New Haven, 2,812 persons with 804 deaths, and in Iowa, 3,673 persons with 763 deaths. At 2 years, odds of death from all causes were higher in the low (less than 130 mmHg) than the middle (130-159 mmHg) systolic blood pressure group for persons aged 65-79 years in all three populations. By 5 years, cardiovascular death increased with increasing systolic pressure in all three communities and reached significance in Iowa. Cancer death was highest in the low systolic pressure stratum in all three centers. All-cause, cardiovascular death, and cancer mortality was highest in the low (less than 75 mmHg) diastolic blood pressure group in East Boston, even at 5 years. Blood pressures obtained 9 years earlier in 2,079 (68%) of the East Boston participants showed a significantly higher risk of cardiovascular death with increasing systolic pressure and no relation between diastolic pressure and mortality risk. In the elderly, excess mortality at lower levels of blood pressure during early follow-up may in part be due to the effects of illness and disability present at baseline. This may obscure the usual rise in mortality with increasing systolic pressure. There is no consistent relation between diastolic pressure and mortality. PMID- 1897507 TI - Incidence rates of firearm injuries in Galveston, Texas, 1979-1981. AB - Firearm injury mortality rates have been characterized in various settings, but little is known of the total magnitude of firearm injury, including morbidity. The authors determined population-based incidence rates of firearm injury among residents of Galveston, Texas, from 1979-1981 by using police, emergency department, hospital, emergency medical services, medical examiner, and vital records to identify 239 firearm injury cases. Vital records, medical examiner, and police records each identified more than 95% of the fatalities, but police records (sensitivity = 98%) were better than emergency department or hospital records (sensitivity = 82% and 28%, respectively) for identifying all nonfatal cases. The annual age-adjusted incidence rate of firearm injury was 128 per 100,000 persons. Black males, with the highest firearm injury rate (459 per 100,000 persons), were injured at 46 times the rate of white females (10 per 100,000 persons). The overall case fatality rate was 30%, including 25% of the assaults/homicides, 81% of the parasuicides/suicides, and 0% of the unintentional injuries. On the basis of the case fatality rates, an estimated 140,000 firearm injuries occur in the United States annually. The case fatality rate for penetrating head injuries was 80% versus 48% for chest injuries and 6% for all other parts of the body. The results are discussed with respect to policy recommendations for reducing firearm injuries. PMID- 1897506 TI - Depressive symptoms among Puerto Ricans: island poor compared with residents of the New York City area. AB - This paper compares the distribution and sociodemographic patterns of depressive symptoms among two groups of Puerto Ricans. The data employed for the analysis are from a probability sample of two communities of adults. Puerto Ricans living in poor residential areas on the Island (n = 1,658) and those living in the New York City area (n = 1,267). The first group was interviewed during 1989, and the second during 1984. Symptoms of depression were measured with the Center for Epidemiologic Studies Depression Scale. Results show that Puerto Ricans residing in the New York City area and the Island poor have similar levels of high depressive symptomatology, 28.1% and 28.6%, respectively. Results of the logistic regression analysis indicated that female sex, low educational level, low household income, and unemployment are predictors of high depressive symptoms for both samples. These results are similar to findings for other ethnic groups. For Puerto Ricans living in New York, the effect of interviewing in Spanish on high depressive symptoms diminishes after sex, education, and income variables are controlled. PMID- 1897508 TI - The draft lottery and AIDS: evidence against increased intravenous drug use by Vietnam-era veterans. AB - To investigate whether intravenous drug use begun during military service might affect risk of acquired immunodeficiency syndrome (AIDS), the authors compared AIDS cases in men eligible to be drafted with those in men who were exempt in the Vietnam-era draft lottery of 1970-1972. Draft-eligible men were less likely to develop AIDS attributed to intravenous drug use than were draft-exempt men (relative risk = 0.87; 95% confidence interval 0.80-0.95; p = 0.001). Other human immunodeficiency virus exposure categories showed no difference between the two groups. These results argue against increased intravenous drug use by Vietnam-era veterans. PMID- 1897509 TI - A longitudinal study of risk factors for depressive symptomatology in elderly widowed and married women. AB - Few studies have examined whether risk factors for depressive symptomatology differ in bereaved and nonbereaved individuals or whether risk factors differ in bereaved individuals over time. Between 1979 and 1983 in Washington County, Maryland, the associations between various health and social network variables and depressive symptomatology were evaluated prior to bereavement and at 1 and 12 months after bereavement in 136 widows and 409 married controls. Prior Center for Epidemiologic Studies Depression Scale scores were generally a good predictor of subsequent scores; however, shortly after bereavement prior scores proved relatively uninformative as most widows experienced a marked increase in depressive symptomatology. Poor health and limitations in physical activity at baseline were consistently associated with higher levels of symptomatology. Although having more friends was also consistently associated with lower levels of symptomatology, the effect of family size appeared to be time and circumstance specific. These results suggest that women at risk of prolonged depression after the death of their husbands can be identified prior to or at the time of bereavement and that widows have risk factors similar to those of women at risk of depression in the general community. PMID- 1897512 TI - Hemopoietic inhibition in hairy cell leukemia. AB - Leukopenia, thrombocytopenia, and anemia are important features of hairy cell leukemia (HCL). They are generally considered to be due to hypersplenism and to inadequate production by bone marrow which is heavily infiltrated by the neoplastic hairy cells (HC). However, the cytopenias may also be caused by hemopoietic inhibition by cytokines derived from the mononuclear cells (MNC) of HCL. We studied the MNC of HCL with an in vitro assay for granulocyte-macrophage progenitors (CFU-GM) to search for this hemopoietic inhibitor(s) and to determine the cell source and mechanism of its production/release. We found that MNC conditioned media from 7 of 9 HCL cases exerted substantial inhibitory effect (23% to 66%) on normal marrow cells. Peak inhibitory activity was obtained in media conditioned with 10(6) MNC/ml for 90 minutes to 24 hours. Both HC and lymphocytes could release inhibitor(s) through mutually synergistic cell interactions. HC alone were inactive and lymphocytes alone were only weakly active. Mixtures of conditioned media of HC and of lymphocytes were not synergistic. The lymphocytes responsible for the inhibition were present in preparations depleted of cells bearing the cluster designation 4 antigen (CD4+) and B cells and were most likely the CD8+ T-cells. In one patient so examined, a partial reversal of inhibition was achieved by treating MNC-CM with antibodies to tumor necrosis factor (TNF)-alpha suggesting that TNF-alpha was at least partly involved in the inhibition of CFU-GM. This mechanism of cytokine release may be operative in vivo to account for the cytopenias in HCL and, if so, could alter the concept of hypersplenism in this disease. PMID- 1897511 TI - A glycosaminoglycan inhibitor of thrombin: a new mechanism for abnormal hemostatic assays in cancer. AB - The isolation and partial characterization of a novel anticoagulant from the plasma of a patient with metastatic prostate cancer is described. The patient had a prolonged activated partial thromboplastic time, prothrombin time and thrombin time which did not correct by mixing with normal plasma. The reptilase time was normal and the prolonged thrombin time was corrected with protamine sulfate suggesting a heparin-like anticoagulant. A glycosaminoglycan anticoagulant (GAC) was isolated from the patient's plasma. The inhibitory activity of the GAC was destroyed by treatment with chondroitinase ABC. The GAC migrated on agarose gel electrophoresis between keratin sulfate and heparan sulfate. Purified GAC possessed only 2% (W/W) of the antithrombin III cofactor activity of porcine heparin. In assays using purified fibrinogen, the GAC was shown to directly inhibit fibrinogen proteolysis by thrombin. It is concluded that this glycosaminoglycan anticoagulant directly inhibits thrombin clotting of fibrinogen and is a new mechanism for abnormal hemostatic assays in cancer. PMID- 1897513 TI - Small non-cleaved cell lymphoma in adults. PMID- 1897510 TI - The effect of two mailing strategies on the response to a survey of physicians. AB - In 1989, the authors tested the effectiveness of two response-enhancing techniques, a postage stamped or franked return envelope and a prenotification letter, in a survey of pregnancy among 10,047 resident physicians in the United States. The techniques were randomly assigned using a factorial design. No significant interactions were observed between the techniques. After two mailings, those who received a stamped return envelope had a response of 71.2%, compared with 68.2% for those who received a franked return envelope (95% confidence interval 1.3-4.9%). Men who received the stamped envelope had a 5.9% greater response than those who received the franked envelope (p less than 0.001), but the type of postage did not influence response among women (p = 0.84); this interaction was statistically significant (p = 0.006). Physicians who received a prenotification letter had a response of 69.0%, compared with 70.5% for those who did not receive the letter (95% confidence interval -3.3 to 0.2%). The authors conclude that seemingly minor changes in survey design could have saved from 12% to 19% of the total cost of the study. PMID- 1897514 TI - Reproducibility and temporal stability of ADP-induced platelet aggregation: comparison of the anticoagulants sodium citrate and D-phenylalanyl-L-prolyl-L arginyl-chloromethyl ketone. AB - We compared the reproducibility and temporal stability of ADP-induced aggregation of platelet-rich plasma anticoagulated with citrate or with D-phenylalanyl-L prolyl-L-arginyl-chloromethyl ketone (PPACK), a thrombin inhibitor. Citrate- or PPACK-platelet-rich plasma (PRP) was stored at room temperature in capped plastic tubes or in plastic syringes from which all air was expelled. At intervals over 1 5 hr after venipuncture, platelet aggregation was induced by 1-1.5 microM ADP. Initially, the aggregation of PPACK-PRP was nearly twice that of citrate-PRP. The response of PPACK-PRP stored in the syringe remained essentially constant over the interval of study, in contrast to the responses of the other samples which declined with time. The improved stability of the response obtained from samples anticoagulated with PPACK was due to the absence of citrate, since PRP containing both citrate and PPACK became less responsive over time in a manner similar to PRP which contained only citrate. Anticoagulation with PPACK rather than citrate results in a more reproducible and stable aggregation response and more closely reproduces the in vivo environment of the platelet. PMID- 1897515 TI - Transient reversal of bone marrow aplasia associated with lymphocyte depleted Hodgkin's disease after combination chemotherapy. AB - This report describes a patient with lymphocyte depleted Hodgkin's disease who presented with bone marrow aplasia. The aplastic marrow reverted to normal after initiation of MOPP chemotherapy; however, 4 months after completion of therapy, bone marrow aplasia recurred in the absence of recurrent Hodgkin's disease. The patient remains free of Hodgkin's disease 34 months after completion of chemotherapy. Bone marrow abnormalities in Hodgkin's disease are reviewed and the current understanding of the pathological mechanisms leading to aplastic anemia is discussed. PMID- 1897516 TI - The effect of 1-hydroxyvitamin D3 for prolongation of leukemic transformation free survival in myelodysplastic syndromes. AB - Leukemic transformation (LT) free survival was studied in 30 patients with myelodysplastic syndromes (MDS). In 15 cases, 4-6 micrograms/day of 1 hydroxyvitamin D3 was administered, for a median duration of 17 months (D-group), other subjects had no therapy (N group). LT free survival of the D group had significant advantage over that of the N group according to the Kaplan-Meier method (P less than 0.001). In addition, 7 cases in the N group developed acute leukemia, in contrast to only one in the D group (P less than 0.05). These results suggest that oral administration of 1-hydroxyvitamin D3 prevents the progression of MDS to overt leukemia under the effect of differentiation capacity from blasts to monocytes. PMID- 1897517 TI - Releasable IgG Fc receptors as activation markers on B-chronic lymphocytic leukemia (B-CLL) cells. PMID- 1897519 TI - The forensic applications of molecular genetics--the journal's responsibility. PMID- 1897518 TI - Molecular characterization of Hb S(C) beta-thalassemia in American blacks. AB - An extension of previous reports describing the molecular defects and hematological abnormalities in black patients with Hb S(C) beta-thalassemia living in the Southeastern United States is presented. As many as 58 patients with Hb S-beta(+)-thalassemia, 16 with Hb C-beta(+)-thalassemia and 12 with Hb S beta(0) -thalassemia have been studied. Patients with Hb S(C) beta(+)-thalassemia type 2 (high Hb A values) were most common; the thalassemia was due to mutations in the promoter of the beta-globin gene [-88 (C----T) and -29 (A----G)] or at the polyadenylation signal (T----C). Two patients with lower Hb A values (type 1) carried a mutation in the first intron of the beta-globin gene (IVS-1-5: G----T). The simultaneous presence of an alpha-thalassemia -2(-alpha/) resulted in some modifications of the hematological parameters, but had a minimal effect on the clinical condition. Patients with Hb S-beta (0) thalassemia had lower hemoglobin values, lower number of red blood cells, and lower MCHC values and suffered more frequently from complications than the patients with Hb S-beta(+)-thalassemia. A total of 17 different beta-thalassemia mutations were observed in 128 chromosomes; two mild beta(+)-thalassemia mutations [-88(C----T) and -29(A----G)] account for more than 80% of the thalassemic chromosomes. PMID- 1897520 TI - Identification of novel rhodopsin mutations associated with retinitis pigmentosa by GC-clamped denaturing gradient gel electrophoresis. AB - Retinitis pigmentosa (RP) is a group of disorders characterized by progressive degeneration of the outer retina, resulting in night blindness, visual field loss, an abnormal electroretinogram, and characteristic retinal pigmentary changes. An important step in the understanding of RP has been the recognition that some cases of autosomal dominant RP (ADRP) are caused by mutations in the rhodopsin gene. Multiple different point mutations within the coding sequence of the rhodopsin gene have been associated with ADRP. We have developed a GC-clamped denaturing-gradient-gel electrophoresis (DGGE) assay for the coding region of the rhodopsin gene and have used this assay to screen ADRP patients for mutations. The assay consists of amplifying with PCR the five exons of the rhodopsin gene and then analyzing each PCR product by DGGE. We have used this assay to detect three previously unreported rhodopsin base substitutions associated with ADRP. The use of this assay to identify ADRP patients who have various rhodopsin mutations has allowed us to begin studies seeking to correlate molecular genotype with clinical phenotype. Furthermore, GC-clamped DGGE has allowed us to identify families with ADRP not caused by a rhodopsin mutation. Such families will be important in the search for other genes involved in ADRP. PMID- 1897521 TI - Detection of deletions and cryptic translocations in Miller-Dieker syndrome by in situ hybridization. AB - Fluorescence in situ hybridization (FISH) using two cosmid probes (41A and P13) from the Miller-Dieker syndrome (MDS) critical region in 17p13.3 was performed in a blinded comparison of three MDS patients with submicroscopic deletions and in four normal relatives used as controls. The controls showed both chromosome 17 homologues labeled in 85%-95% of cells, while each patient showed only one homologue labeled in 75%-80% of cells. Two MDS patients with cryptic translocations were also studied. In one case, a patient and her mother had the same der(17) (p+), but the reciprocal product of the translocation could not be identified in the mother by G-banding (i.e., it was a "half-cryptic" translocation). FISH revealed a 3q;17p translocation. The other case involved a patient with apparently normal karyotype. Because a large molecular deletion was found, a translocation involving two G-negative telomeres (i.e., a "full-cryptic" translocation) was postulated. FISH studies on her father and normal brother showed an 8q;17p translocation. These studies demonstrate that in situ hybridization is an efficient method for deletion detection in Miller-Dieker syndrome. More important, parental studies by FISH on patients demonstrating molecular deletions and a normal karyotype may identify cryptic translocation events, which cannot be detected by other molecular genetic strategies. Similar in situ strategies for deletion detection can be developed for other microdeletion syndromes, such as Prader-Willi/Angelman syndrome or DiGeorge syndrome. PMID- 1897522 TI - DNA typing and genetic mapping with trimeric and tetrameric tandem repeats. AB - Tandemly reiterated sequences represent a rich source of highly polymorphic markers for genetic linkage, mapping, and personal identification. Human trimeric and tetrameric short tandem repeats (STRs) were studied for informativeness, frequency, distribution, and suitability for DNA typing and genetic mapping. The STRs were highly polymorphic and inherited stably. A STR-based multiplex PCR for personal identification is described. It features fluorescent detection of amplified products on sequencing gels, specific allele identification, simultaneous detection of independent loci, and internal size standards. Variation in allele frequencies were explored for four U.S. populations. The three STR loci (chromosomes 4, 11, and X) used in the fluorescent multiplex PCR have a combined average individualization potential of 1/500 individuals. STR loci appear common, being found every 300-500 kb on the X chromosome. The combined frequency of polymorphic trimeric and tetrameric STRs could be as high as 1 locus/20 kb. The markers should be useful for genetic mapping, as they are sequence based, and can be multiplexed with the PCR. A method enabling rapid localization of STRs and determination of their flanking DNA sequences was developed, thus simplifying the identification of polymorphic STR loci. The ease by which STRs may be identified, as well as their genetic and physical mapping utility, give them the properties of useful sequence tagged sites (STSs) for the human genome initiative. PMID- 1897523 TI - Localization of one gene for tuberous sclerosis within 9q32-9q34, and further evidence for heterogeneity. AB - Tuberous sclerosis (TSC) is an autosomal dominant disorder with both neurological and cutaneous manifestations often resulting in significant disability. Although it has been studied clinically and biochemically for many years, the underlying pathophysiology remains unknown. Genetic linkage analysis provides an alternative strategy for understanding the genetic etiology of this disease. Genetic linkage of a gene for TSC to loci in 9q32-9q34 has been reported but has not been a universal finding, since absence of linkage to 9q loci, as well as linkage to loci on 11q, have also been reported. We present here data on 22 families (21 previously unreported) segregating TSC. Our results strongly support a TSC locus in the 9q32-34 region for approximately one-third of families and provide significant evidence for genetic heterogeneity. Application of newly described highly polymorphic dinucleotide repeat marker loci in TSC greatly enhanced the informativeness of our pedigrees and was vital for detecting the heterogeneity. No clear evidence of linkage to chromosome 11q22 markers was found, suggesting that a still unidentified TSC locus elsewhere in the genome may account for the majority of TSC families. PMID- 1897524 TI - Regressive logistic models for familial diseases: a formulation assuming an underlying liability model. AB - Statistical models have been developed to delineate the major-gene and non-major gene factors accounting for the familial aggregation of complex diseases. The mixed model assumes an underlying liability to the disease, to which a major gene, a multifactorial component, and random environment contribute independently. Affection is defined by a threshold on the liability scale. The regressive logistic models assume that the logarithm of the odds of being affected is a linear function of major genotype, phenotypes of antecedents and other covariates. An equivalence between these two approaches cannot be derived analytically. I propose a formulation of the regressive logistic models on the supposition of an underlying liability model of disease. Relatives are assumed to have correlated liabilities to the disease; affected persons have liabilities exceeding an estimable threshold. Under the assumption that the correlation structure of the relatives' liabilities follows a regressive model, the regression coefficients on antecedents are expressed in terms of the relevant familial correlations. A parsimonious parameterization is a consequence of the assumed liability model, and a one-to-one correspondence with the parameters of the mixed model can be established. The logits, derived under the class A regressive model and under the class D regressive model, can be extended to include a large variety of patterns of family dependence, as well as gene environment interactions. PMID- 1897525 TI - Linkage analysis of quantitative traits: increased power by using selected samples. AB - Although a number of methods have been developed for linkage analysis of quantitative traits, power is relatively poor unless there is a single major locus of very large effect. Here it is demonstrated that the use of selected samples (i.e., ascertainment of a proband with an extreme score on the quantitative measure) can dramatically increase power, especially when proband selection is performed on the tail of a distribution with an infrequent recessive gene. Depending on gene action and allele frequency, selected samples permit detection of a major locus that accounts for as little as 10%-20% of the phenotypic variation. The judicious use of selected samples can make an appreciable difference in the feasibility of linkage studies for quantitative traits. PMID- 1897526 TI - Lowe oculocerebrorenal syndrome in a female with a balanced X;20 translocation: mapping of the X chromosome breakpoint. AB - A Hispanic girl with Lowe oculocerebrorenal syndrome (OCRL), an X-linked recessive condition characterized by cataracts, glaucoma, mental retardation, and proteinuria, is reported. A balanced X;20 chromosomal translocation with the X chromosome breakpoint at q26.1 was found with high-resolution trypsin-Giemsa banding. Somatic cell hybridization was used to separate the X chromosome derivative and the chromosome 20 derivative in order to position, with respect to the translocation breakpoint, several DNA loci that are linked to the Lowe syndrome locus (Xq24-q26). DXS10 and DXS53 were found to be distal to the breakpoint, whereas DXS37 and DXS42 were located proximal to it. These studies suggest that the OCRL locus lies in the region between these probes. The translocation chromosome originated from an unaffected male without a visible translocation, indicating that the most likely cause of OCRL in this patient is the de novo translocation that disrupted the OCRL locus. PMID- 1897527 TI - Deletions within the pseudoautosomal region help map three new markers and indicate a possible role of this region in linear growth. AB - Short stature is consistently found in individuals with terminal deletions of Xp. In order to refine the localization of a putative locus affecting height, we analyzed two patients with a partial monosomy of the pseudoautosomal region at the molecular level. Eight pseudoautosomal probes were used for the genetic deletion analysis through dose evaluation. Three of them represent new markers (DXS415, DXS419, and DXS406) which were positioned on the pseudoautosomal map by pulsed field gel electrophoresis. Our data suggest that a locus affecting height maps in a region of about 1.5 Mbp, distal to the DXS406 locus and proximal to the DXS415 locus, a region which includes two CpG islands, and rule out an involvement of very distal sequences at the X/Y telomeres. PMID- 1897528 TI - Why does the human factor IX gene have a G + C content of 40%? AB - The factor IX gene has a G + C content of approximately 40% in all mammalian species examined. In human factor IX, C----T and G----A transitions at the dinucleotide CpG are elevated at least 24-fold relative to other transitions. Can the G + C content be explained solely by this hot spot of mutation? Using our mathematical model, we show that the elevation of mutation at CpG cannot alone lower the G + C content below 45%. To search for other hot spots of mutation that might contribute to the reduction of G + C content, we assessed the relative rates of base substitution in our sample of 160 families with hemophilia B. Seventeen independent single-base substitutions are reported herein for a total of 96 independent point mutations in our sample. The following conclusions emerge from the analysis of our data and, where appropriate, the data of others: (1) Transversions at CpG are elevated an estimated 7.7-fold relative to other transversions. (2) The mutation rates at non-CpG dinucleotides are remarkably uniform; none of the observed rates are either more than twofold above the median for transitions or more than threefold above the median for transversions. (3) The pattern of recent mutation is compatible with the pattern during mammalian evolution that has maintained the G + C content of the factor IX gene at approximately 40%. PMID- 1897529 TI - High frequency of the Gaucher disease mutation at nucleotide 1226 among Ashkenazi Jews. AB - Reliable estimates of the frequency of Gaucher disease-producing mutations are not available. The high frequency of Gaucher disease in the Ashkenazi Jewish population is due to the occurrence of a mutation at nucleotide (nt) 1226. We have screened 593 DNA samples from normal Ashkenazi Jews, as well as 62 DNA samples from all our Ashkenazi Jewish patients with Gaucher disease, for the presence of the 1226 mutation. In the 593 presumed normal Ashkenazi Jewish individuals the 1226 mutation was identified in the heterozygous state in 37 and in the homozygous state in two, giving a gene frequency of .035 for the mutation. This 1226 mutation represented 73% of the 124 Gaucher disease alleles in Jewish Gaucher disease patients. Accordingly we estimate that the gene frequency for Gaucher disease among the Ashkenazi Jewish population is .047, which is equivalent to a carrier frequency of 8.9% and a birth incidence of 1:450. PMID- 1897530 TI - Molecular characterization of two galactosemia mutations: correlation of mutations with highly conserved domains in galactose-1-phosphate uridyl transferase. AB - Galactosemia is an autosomal recessive disorder of human galactose metabolism caused by deficiency of the enzyme galactose-1-phosphate uridyl transferase (GALT). The molecular basis of this disorder is at present not well understood. We report here two missense mutations which result in low or undetectable enzymatic activity. First, we identified at nucleotide 591 a transition which substitutes glutamine 188 by arginine. The mutated glutamine is not only highly conserved in evolution (conserved also in Escherichia coli and Saccharomyces cerevisiae), but is also two amino acid residues downstream from the active site histidine-proline-histidine triad and results in about 10% of normal enzymatic activity. The arginine 188 mutation is the most common galactosemia mutation characterized to date. It accounts for one-fourth of the galactosemia alleles studied. Second, we report the substitution of arginine 333 by tryptophan, caused by a transition at nucleotide 1025. The area surrounding this missense mutation is the most highly conserved domain in the homologous enzymes from E. coli, yeast, and humans, and this mutation results in undetectable enzymatic activity, suggesting that this is a severe mutation. This second mutation appears to be rare, since it was found only in the patient we sequenced. Our data provide further evidence for the heterogeneity of galactosemia at the molecular level, heterogeneity which might be related to the variable clinical outcome observed in this disorder. PMID- 1897531 TI - A response to Lander: the courtroom perspective. PMID- 1897532 TI - DNA fingerprinting. PMID- 1897533 TI - Research on DNA typing validated in the literature. PMID- 1897535 TI - Panel recommends independence, more resources for FDA. PMID- 1897534 TI - Screening for the major cystic fibrosis mutation in non-Caucasian populations. PMID- 1897536 TI - Rethinking the term "intervention". PMID- 1897537 TI - Material safety data sheets for investigational drugs. PMID- 1897538 TI - Educational qualifications of hospital pharmacy managers. PMID- 1897539 TI - Stability of amphotericin B in 5% dextrose injection at 25 degrees C. PMID- 1897540 TI - Standardized cancer chemotherapy order form. PMID- 1897541 TI - Drug information services provided by pharmaceutical manufacturers. PMID- 1897542 TI - No more animal research. PMID- 1897543 TI - Do not forget medical staff education. PMID- 1897545 TI - Lest we forget. PMID- 1897544 TI - Comments on levels of pharmaceutical care. PMID- 1897546 TI - Ethics of cardiac transplantation. PMID- 1897547 TI - Pharmaceutical promotion and pharmacist probity. PMID- 1897548 TI - Harvey A. K. Whitney Lecture. To a new beginning from converging paths. AB - The implementation of the pharmaceutical care concept is discussed. Current activities of professional pharmacy organizations are laying the groundwork for the new emphasis on patient outcomes, which is seen in the mission statements of the American Pharmaceutical Association (APhA) and the Joint Commission of Pharmacy Practitioners (JCPP). APhA is revalidating its standards of practice; the American Association of Colleges of Pharmacy (AACP) has formed a Commission to Implement Change in Pharmaceutical Education; the American Council on Pharmaceutical Education (ACPE) is revising its standards to be consistent with entry-level practitioners' ability to provide pharmaceutical care and seeking ways in which pharmacists currently practicing in all sites can upgrade their skills. These groups are called on to implement pharmaceutical care: To make known the "value-added services" encompassed in pharmaceutical care, JCPP should market to the public its concept of pharmacists' mission. APhA should analyze pharmaceutical services currently provided and promote postgraduate training programs in pharmaceutical care. ACPE must focus on ways pharmacists can achieve the competencies required for pharmaceutical care, and AACP must ensure that academic programs are consistent with the needed competencies. ASHP should hold a national conference on implementation of pharmaceutical care, create a commission for this purpose, direct more effort at pharmacists practicing in nonhospital settings, and accelerate its clinical skills development program. Employers should put less emphasis on "clinical" designations and Pharm.D. degrees and more on the ability to provide pharmaceutical care. Implementation of pharmaceutical care is imperative. PMID- 1897549 TI - Expansion of clinical pharmacy services through staff development. AB - A program that trains and uses staff pharmacists for clinical services is described. A position was created that is filled by staff pharmacists on six-week rotations. All full-time pharmacists may participate; they work under the direction and supervision of clinical pharmacists. Basic responsibilities in the rotation include responding to drug information requests, assisting with drug-use evaluation and adverse drug experience programs, assisting with research, writing and editing for newsletters, participating in staff development programs, and reviewing and clarifying drug orders for the skilled-nursing facility. About 60% of eligible pharmacists have participated in this program. The pharmacists have gained new practice skills, greater opportunity for career enhancement, and improved attitudes toward work and colleagues, and the department has been able to provide more clinical services. The focus of the rotation is now being changed from performing clinical tasks to assuming more responsibility for patient outcomes related to drug therapy. A rotating clinical position has enabled staff pharmacists to gain additional nondispensing skills and contribute to the development and maintenance of clinical services. PMID- 1897550 TI - Expanding staff pharmacists' responsibilities to maintain pharmacy services in a neonatal intensive-care unit. AB - The conversion of pharmacist responsibilities in a neonatal intensive-care unit (NICU) pharmacy satellite from drug distribution to both clinical services and drug distribution is described. When the pharmacy department could not recruit a specialty-trained clinical practitioner to fill an open NICU position, the position was converted to a fourth satellite pharmacist position, and each of the four NICU satellite pharmacists assumed clinical responsibilities for the NICU. Clinical and distributive functions had previously been separate. Staff development programs and a contract with the previous NICU clinical practitioner for consultative services helped to ease the transition. NICU pharmacists currently provide inservice education to medical residents and the nursing staff, provide drug information, monitor drug therapy, perform pharmacokinetic monitoring, are involved in research, and work to streamline satellite operations. For one of every four months, the NICU pharmacists primarily provide clinical services; the remainder of the time clinical activities are combined with drug distribution responsibilities. The staffing schedule has enabled the department to extend the hours that clinical services are available. The NICU pharmacists maintain secondary areas of staffing, and other pharmacists periodically staff the NICU satellite. Staff pharmacists in the NICU pharmacy satellite developed clinical skills that permitted integration of clinical and distributive pharmacy services. PMID- 1897551 TI - Comprehensive drug-use evaluation program in a health maintenance organization. AB - Development and use of a drug-use evaluation (DUE) program for hospital and outpatient facilities of a health-maintenance organization (HMO) are described. A full-time pharmacist coordinates the DUE program. Primary components of the DUE program are (1) establishment and use of drug therapy management protocols, (2) periodic review and evaluation of drug-use statistics by the pharmacy and therapeutics (P&T) committee, (3) monitoring of pharmacist interventions, and (4) evaluation of specific drug use within individual medical staff departments. Information from all DUE activities is channeled through the P&T committee and linked to the HMO's overall quality assurance program. The DUE program has the support of the HMO physicians. It has enhanced the quality of drug use and identified opportunities to further improve the quality of patient care. In surveys by the Joint Commission on Accreditation of Healthcare Organizations, the HMO facilities have received no recommendations. Pharmacists and physicians have cooperated to develop a comprehensive DUE program for an HMO. PMID- 1897552 TI - Promoting residencies to pharmacy students. AB - A program for promoting pharmacy residency training to pharmacy students at the University of the Pacific (UOP) is described. A residency club was started in 1982 to increase UOP students' interest in residency training and to provide them with relevant information. Some students needed to be convinced that residencies were primarily educational rather than staffing experiences. Students were made aware of pharmacists' practice in specialty areas, for which residency training is needed, and were taught how to prepare themselves for selection for residencies. The club was formed to encourage mutual support among the students, which would be less likely to occur if residencies were promoted only through work with individual students. Club meetings provide information about available residencies, the application process, and the value of residency training to a career in pharmacy. Students are taught how to prepare curricula vitae, how to interview, and how to select programs to which to apply. Applications for residencies increased. Although the rate of acceptance was low at first, it was expected to increase as more UOP students demonstrated their interest in and qualification for residency training. The promotion of residencies as part of a balanced career planning and placement program for pharmacy students is encouraged. PMID- 1897553 TI - Case report: Crouzon syndrome with short stature. AB - A five-year-old boy with Crouzon Syndrome, short stature, and delayed bone age was found to have partial growth hormone deficiency. Accelerated growth was observed after human growth hormone replacement. Children with Crouzon Syndrome should be followed closely for all growth parameters, not just head circumference. PMID- 1897555 TI - Case report: epidural and bilateral retroorbital hematomas complicating sickle cell anemia. AB - Early in the course of a painful crisis, a 19-year-old man with known sickle cell anemia (SCA) developed a clinical picture that resembled either early cavernous sinus thrombosis or retroorbital and bifrontal microinfarcts. A brain computer tomography scan demonstrated bilateral retroorbital hemorrhages along with a left frontal epidural hematoma. In the absence of trauma, thrombocytopenia, or any other detectable hemostatic defect, this type of hemorrhagic manifestation in the setting of SCA has not, to our knowledge, been previously reported in the literature. PMID- 1897554 TI - Case report: hepatic hydrothorax without ascites. AB - Pleural effusion due to hepatic cirrhosis and ascites is well known. We describe three patients with right-sided hepatic hydrothorax in the absence of ascites. The formation of pleural fluid in these patients is probably a result of fluid movement from peritoneal to pleural space across diaphragmatic defects before ascites can form. The differential diagnosis of a right-sided transudative pleural effusion in a patient with chronic liver disease with or without ascites includes congestive left ventricular failure and nephrotic syndrome. These diseases are usually ruled out with standard clinical tests. Patients with hepatic hydrothorax should be treated with fluid restriction and diuretics. Patients with severe symptoms due to refractory hepatic hydrothorax might benefit from pleural sclerosis and surgical closure of diaphragmatic defects. PMID- 1897556 TI - Endocrine manifestations of human immunodeficiency virus (HIV) infection. AB - Endocrine manifestations of HIV infection include both pathological changes and disturbances in function. Mechanisms include direct infection of glands by HIV or opportunistic organisms, infiltration by neoplasms, side effects of drugs, and production of humoral factors that may alter metabolism. The adrenal gland is most often affected, but virtually every endocrine system may be involved. Dysfunction is often subtle, with symptoms overlapping those of the HIV infection itself. Endocrine manifestations may be found at any time in the course of the disease, from the asymptomatic HIV-positive stage through full-blown AIDS. Optimal management of these patients may include a careful search for, and appropriate treatment of, associated endocrine abnormalities. PMID- 1897557 TI - Duchenne's muscular dystrophy: review and recent scientific findings. AB - In this brief review, we describe the clinical manifestations of Duchenne's muscular dystrophy (DMD) and other similar syndromes, outline the history of the dystrophin gene's identification and its relationship to these muscular dystrophies, and relate the importance of the gene's discovery to clinical neurology. We do not discuss treatment. PMID- 1897558 TI - The Duke Minority Medical Student Summer Fellowship: one program's attempt to attract minority residents. AB - Despite numerous Federal and private funding programs aimed at increasing the numbers of underrepresented minorities in medicine, the participation of minority groups in the medical profession remains low and shows little sign of improvement. With the goal of improving minority representation in our primary care residency program, the Minority Medical Student Summer Fellowship started in July 1990. The program's purpose is to give minority medical students positive exposure to primary care and attract them back for residency training. In this four-week elective, students participate in seminars with our primary care residents, see patients in a variety of clinics, and complete a project. Key implementation issues include support of the medicine chairman and dean, funding, and malpractice coverage for the students. Program evaluation from the first two students rated the clinic experiences higher than the seminar sessions and the independent project. Both students stated our fellowship made them more likely to train at this medical center should they enter a primary care program. Implications for other programs are listed. PMID- 1897559 TI - Fluconazole: a new triazole antifungal agent. AB - Fluconazole is a recently approved agent for the treatment of certain fungal infections. Based on available studies, the drug is clearly effective in oropharyngeal candidiasis in immunosuppressed hosts. Current evidence suggests it may be more efficacious than other azole drugs for oropharyngeal disease. It is probably also effective in other infections due to Candida species, but controlled studies are lacking. Fluconazole is also efficacious in the treatment of cryptococcal meningitis, but recent reports question its use as initial therapy in HIV-infected patients with this illness. The drug, however, is clearly more effective than amphotericin B in the suppression of cryptococcal meningitis in AIDS patients and is the treatment of choice in this situation. PMID- 1897561 TI - A dose-related curve of wound tensile strength following ultraviolet irradiation in the hairless guinea pig. AB - A dose-related curve of wound tensile strength was derived following exposure to three doses of predominantly UVA (Ultraviolet A) radiation (98.3% between 315 nm and 400 nm, 1.7% less than 315 nm). Forty female hairless guinea pigs were divided into four equal groups: Group 1 (controls); Group 2 (40 J[Joules]/cm2/day); Group 3 (80 J/cm2); and Group 4 (160 J/cm2). Preoperatively, the experimental groups were irradiated on alternate days for 16 weeks. Serial dorsal punch biopsies (4 mm) were taken prior to the initial exposure and subsequently at 2, 4, 8, 12, and 16 weeks and examined histologically and microscopically. Then, standard 6 cm midline dorsal surgical wounds were made and allowed to heal for 21 days. Wounds were excised and wound tensile strength was assessed. Significant decreases (p less than .05) were noted in wound tensile strength of Groups 2, 3, and 4 compared to the controls, with the decrease being directly related to the dose received. Dermal changes were noted in all irradiated groups as early as four weeks after initial UVA/B exposure. Electron microscopy revealed elastosis and disruption of collagen fibers. Prolonged exposure to radiation, predominantly in the UVA range, appears to impede wound healing in a dose-related fashion and elicits elastosis and collagen disruption. PMID- 1897560 TI - Effects of bicarbonate supplementation on urinary mineral excretion during very low energy diets. AB - Metabolic acidosis is associated with increased calciuria and ammoniagenesis. This study evaluated the effects of oral sodium bicarbonate (NaHCO3) or combined potassium bicarbonate-calcium carbonate supplementation on urinary mineral excretion during the ketoacidosis of a very-low-energy protein diet. Seventeen healthy obese subjects (BMI: 37.5 +/- 3.2 kg/m2, weight: 100 +/- 3 kg) were given a 1.72 MJ all protein (93 g) liquid formula and a multivitamin-mineral supplement daily for 3 weeks. Subjects in groups 1 (n = 6) and 2 (n = 5) received 16 mmol KCl. In addition, subjects in group 1 received 60 mmol Na+ daily as sodium chloride, subjects in group 2, 60 mmol Na+ as NaHCO3. The subjects in group 3 (n = 6) were given 32 mmol K+ as bicarbonate and 16 mmol Ca++ as carbonate daily. Metabolic acidosis was prevented in groups 2 and 3 with bicarbonate and bicarbonate-carbonate administration. This was reflected in significant curtailment of the augmented ammonium nitrogen excretion found in group 1. The additional oral K+ in group 3 improved K+ balance and probably also inhibited ammoniagenesis. Urine calcium was greater (p less than 0.04) in group 1 subjects, but similar in groups 2 and 3, despite higher calcium intake in group 3. Urinary phosphorus decreased with time in all groups, but more so in the group 2 subjects who received NaHCO3. Acidosis was associated with the reverse effect on urinary magnesium, which decreased in group 1 subjects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1897562 TI - Defibrillation efficacy using two low-profile endocardial electrodes. AB - The hypothesis that improved energy delivery and defibrillation efficacy can be achieved by using two widely separated endocardial electrodes and a cutaneous patch electrode was explored by positioning two 6.5 F electrodes (NuMed, Hopkinton, New York) with 5 cm platinum-iridium coils in the right ventricular apex (RVA) and the right ventricular outflow (RVO) in eight dogs. In another 12 dogs, an additional electrode was positioned in the RVA. A cutaneous patch (P) was placed at the cardiac apex. Biphasic pulses were delivered, the first pulse (6 ms) positive, the second negative (2 ms). The leading edge of the second was equal to the trailing edge of the first. RVO-/P+ and RVA-RVO-/P+ were compared with RVA-/P+ at a constant voltage setting required to achieve a 60% probability of success (P60) for RVA-/P+. At a constant voltage output, the probability of success for RVA-RVO-/P+ was significantly higher (81%) than RVO-/P+ (60%) or RVA /P+ (67%) (p less than 0.03). The current delivered was greater for RVA-RVO-/P+ (9.9 +/- 2.3 amps) than for either RVA-RVO-/P+ (8.7 +/- 1.9 amps) or RVO-/P+ (9.0 +/- 2.0 amps) (p less than 0.0001). Similarly, the impedance was significantly lower for RVA-RVO-/P+ (66 +/- 12 omega) than for RVA-/P+ (75 +/- 12 omega) and RVO-/P+ (72 +/- 9.6 omega) (p less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1897563 TI - Case report: hypothyroidism due to pneumocystis carinii thyroiditis in a patient with acquired immunodeficiency syndrome. AB - Pneumocystis carinii is the most common cause of opportunistic pulmonary infection in AIDS patients and disseminated disease is being recognized with increasing frequency. We describe a patient with cavitary pulmonary disease, lymphadenopathy, thyroiditis, and associated hypothyroidism, all a result of P. carinii. The organism was easily demonstrated in a fine-needle aspirate specimen of the thyroid. This is the second reported case of clinically apparent Pneumocystis thyroiditis and the first reported case of hypothyroidism due to an opportunistic infection in a patient with AIDS. Clinicians should be aware of this entity and request a Grocott-Gomori methenamine-silver nitrate stain of appropriate cytology specimens to make the diagnosis. PMID- 1897564 TI - Patient with multiple congenital anomalies and decreased production and processing of procollagen in cultured fibroblasts. AB - We report on a patient with hip and elbow dislocations, joint hyperextensibility, peculiar facial appearance, torticollis, cryptorchidism, unilateral hexadactyly, and other minor anomalies. Cultured cells from this patient produce less type I procollagen and have a slower rate of processing of type I procollagen to collagen in the culture medium. We think that the pattern of clinical anomalies constitutes a previously unreported syndrome with type I procollagen defect as a manifestation of the syndrome. PMID- 1897565 TI - Hyperekplexia: pedigree studies in two families. AB - We report on 2 unrelated Japanese families, each with several individuals affected with hyperekplexia, a rare autosomal dominant form of exaggerated startle response of neonatal onset. In the first family, affected relatives included a 4-week-old boy, his mother, grandmother, a maternal uncle, and 2 maternal cousins. In the second family, affected were a 4-week-old boy, his father, and an elder brother. These 9 individuals had various combinations of transient infantile hypertonia and hypokinesia, exaggerated startle response with falling episodes, nocturnal myoclonus and an easily elicited head retraction reflex, hip dislocation, and umbilical hernia. Treatment with clonazepam was effective in relieving these manifestations in the affected infants and children. Genetic analysis of these 2 families and 4 others in the literature suggests autosomal dominant inheritance with considerable variability but complete penetrance. Another 3 families in the literature were reported, suggesting the existence of startle disorder with an autosomal recessive inheritance. A sporadic case is also known, presumably representing a fresh mutation of a dominantly inherited trait. PMID- 1897566 TI - Osteodysplastic variant of primordial dwarfism. AB - A patient with intrauterine growth retardation and marked postnatal retardation of growth had microcephaly and the orofacial and dental characteristics of the Seckel phenotype. In addition she had short forearms, metaphyseal flare, especially of the distal femora, triangular distal femoral epiphyses, and pseudoepiphyses of the hands, all characteristics of an osteodysplastic variant. Parental consanguinity suggests autosomal recessive inheritance. PMID- 1897567 TI - Holoprosencephaly as a possible embryonic alcohol effect. AB - Three mothers of infants with holoprosencephaly consumed alcohol heavily in pregnancy. We postulate that early alcohol exposure is a possible cause of their malformation. The 3 mothers consumed alcohol only in the first trimester but the first mother continued to take chlordiazepoxide and imipramine throughout the pregnancy. Her infant had an alobar holoprosencephaly associated with a median cleft lip, ocular hypotelorism, and a flat nose. The other infants had semilobar holoprosencephaly and hydrocephalus. These latter 2 infants did not show the characteristic facies of the fetal alcohol syndrome. G-band chromosome studies were normal in all 3 infants. The association of holoprosencephaly with alcohol exposure during pregnancy in humans has been mentioned only briefly, although this malformation has been induced by alcohol in animals. These 3 infants may support the hypothesis that acute or subacute heavy alcohol exposure early in pregnancy could lead to holoprosencephaly without the necessity of a chronic alcohol exposure and without necessarily causing the typical facial findings of the fetal alcohol syndrome. PMID- 1897568 TI - On the inheritance of primary spontaneous pneumothorax. AB - We report on 15 families with familial primary spontaneous pneumothorax detected through a retrospective study of a large group of male patients. Genetic analysis of these families together with 14 families from the literature in which enough details were available suggested 2 possible models of inheritance. First, the familial cases are due to an autosomal dominant gene with incomplete penetrance, the penetrance being lower in females (21%) than in males (50%). Second, the familial cases represent a heterogeneous group of patients: some of the familial cases are due to an X-linked recessive gene and others to an autosomal dominant gene with the incomplete penetrance (35% in females and 50% in males). The second model may explain the excess of female carriers found in the families of the patients and is supported by the existence of clinical differences between the patients in each of the sub-groups. In particular the number of episodes of pneumothorax per patient was significantly higher in the sub-group with the autosomal dominant form than in the sub-group with the X-linked recessive form of the disease. PMID- 1897569 TI - Noonan-like/multiple giant cell lesion syndrome. AB - A patient with the Noonan-like/multiple giant cell lesion syndrome is reported and the findings in 14 cases are reviewed. Impressive manifestations include short stature, low normal intelligence or developmental delay, ocular hypertelorism, prominent posteriorly angulated ears, giant cell lesions of bones, joints, and/or soft tissues, pectus excavatum, and pulmonic stenosis. It has been difficult to delineate the syndrome because problems in identifying the condition have resulted from incomplete or truncate ascertainment by various medical specialists. PMID- 1897570 TI - Robin sequence with facial and digital anomalies in two half-brothers by the same mother. AB - Two half-brothers by the same mother presented with the Robin sequence and facial and digital anomalies. The mother has a normal face and mild hyperopia without abnormality on radiographs of the hands, feet, and pelvis. The older son is 4 years and the younger is 6 months old. Both have normal psychomotor development. To the best of our knowledge this familial association has not been reported before and probably represents a previously unrecognized heritable malformation syndrome. The occurrence of the syndrome in 2 half-brothers by the same unaffected mother suggests X-linked recessive inheritance. PMID- 1897571 TI - Apparent Opitz BBBG syndrome with a partial duplication of 5p. AB - We describe a patient with a paracentric inversion and partial duplication of chromosome 5p. In addition this patient presented with a malformation pattern consistent with Opitz BBBG syndrome. This implies that the gene responsible for this single gene defect may be located within this duplicated region. PMID- 1897572 TI - Osteochondrodysplasia with rhizomelia, platyspondyly, callosal agenesis, thrombocytopenia, hydrocephalus, and hypertension. AB - A female infant born at term to phenotypically normal nonconsanguinous parents had hypertension, thrombocytopenia, hydrocephalus, callosal agenesis, and nonlethal rhizomelic osteochondrodysplasia. Her osteochondrodysplasia was characterized roentgenographically by shortening and metaphyseal broadening of long bones, without bowing, and by platyspondyly, with deficient ossification of dorsal and central portions of vertebral bodies. By light microscopy, the iliac crest growth plate showed expansion of the zone of chondrocyte hypertrophy and degeneration, with faulty columnar alignment, sparse vascular ingrowth, and irregular mineralization at the zone of chondroosseous transformation. These findings appear to define a novel osteochondrodysplasia, which in association with hypertension, thrombocytopenia, hydrocephalus, and callosal agenesis may constitute a new syndrome. PMID- 1897573 TI - Familial posterior helical ear pits and Wiedemann-Beckwith syndrome. AB - Multiple cases of posterior helical ear pits (PHEP) with apparent autosomal dominant inheritance in a very large family are reported. There are at least 2 cases of Wiedemann-Beckwith syndrome (WBS) within this family. Three other instances of familial PHEP and/or WBS are presented. An individual with a somewhat atypical osteopetrosis and PHEP is described. The previous literature of PHEP and the association with WBS is reviewed. PMID- 1897574 TI - Di George anomaly associated with a de novo Y;22 translocation resulting in monosomy del(22)(q11.2). AB - We report on an infant, born to a diabetic mother, who presented with hypocalcemia and congenital heart disease, presurgically diagnosed by echocardiography as truncus arteriosus type I. Cytogenetic analysis showed a 45,X,-Y,-22,+der-(Y)t(Y;22) (p11.3q11.2) chromosome abnormality with del(22)(q11.2). Parental chromosomes were normal. Autopsy showed persistent truncus arteriosus type II and thymic aplasia consistent with DiGeorge anomaly. This report adds to the existing literature demonstrating an association between DiGeorge anomaly and monosomy 22q11. PMID- 1897575 TI - Urofacial syndrome associated with hydrocephalus due to aqueductal stenosis. AB - The urofacial syndrome is an autosomal recessive disorder of distorted facial expression and neurogenic bladder with resultant urogenital tract damage. We report on an 8-year-old boy of consanguineous Arab parents with inverted facial expression upon laughing and renal changes as a consequence of a neurogenic bladder in addition to hydrocephalus due to stenosis of the aqueduct of Sylvius. We suggest that the association is not fortuitous and probably widens the spectrum of urofacial syndrome or represents a distinct entity mimicking the urofacial syndrome. PMID- 1897576 TI - Familial holoprosencephaly associated with a translocation breakpoint at chromosomal position 7q36. AB - A familial balanced t(7;9) (q36;q34) was reported recently. Analysis of the craniofacial features of 3 of the sibs showed signs of holoprosencephaly. Two of the sibs have an unbalanced derivative chromosome leading to del(7) (q36) and dup(9) (q34), while the other has a cytogenetically balanced translocation. These findings, together with several reports associating holoprosencephaly with terminal 7q deletions, indicate that a putative locus for holoprosencephaly resides at or near 7q36. It should now be feasible to clone this locus. PMID- 1897577 TI - Dietary management reverses grooving and abnormal polarization of hair shafts in argininosuccinase deficiency. AB - We have observed that the fragile hair of two untreated patients with argininosuccinic aciduria showed abnormal alternating zones of bright and dark banding by polarizing microscopy. Scanning electron microscopy documented discontinuous grooves with a 50 to 100 microns periodicity. Results of amino acid analysis of the hair were essentially normal. After the patients were treated with a low-protein, arginine-supplemented diet, the hair assumed a normal appearance. Five patients already treated with diet showed no hair abnormalities. The pathogenesis of the hair changes in unknown, but our findings suggest that products generated in the disease can adversely affect metabolically active tissue such as hair. PMID- 1897578 TI - Short rib syndrome--Beemer type in sibs. AB - The short rib (polydactyly) syndrome Beemer type is a rare lethal osteochondrodysplasia characterized clinically by short limbs, median cleft upper lip and palate, narrow thorax, and protuberant abdomen, and radiologically by short ribs, short and bowed long bones, and mild platyspondyly. Two affected female sibs are described, one having a preaxial polydactyly of the feet. The differentiation with the short rib syndrome Majewski type relies mainly on the radiological appearance of the tibia. Molecular biology may eventually prove whether the 2 conditions are truly separate entities or not. PMID- 1897579 TI - Neuropsychological, psychiatric, and physical manifestations in 149 members from 18 fragile X families. AB - One hundred forty-nine subjects from 18 families with fragile X [fra(X)] syndrome were evaluated for their neuropsychological, psychiatric, and physical characteristics. The 36 fra(X) males had intelligence quotients ranging from less than 20 to 61, which prevented the delineation of a reliable neuropsychological profile. Behaviour fitted DSM-III-R and ADI diagnostic criteria of autism in only 2 subjects, both with very low intelligence level (IQ less than 20). Of 36 heterozygotes (HZ), 22 had an IQ between 20 and 80 and 14 between 81 and 99. The neuropsychological profile of the latter was compared with IQ-age-environment matched 14 normal females and 14 normal males. Significantly poorer results in HZ were found on immediate digit memory and on Raven's progressive matrices (a visuo spatial test of logical capabilities). The latter result, in conjunction with those results on the Bender visual-motor gestalt test and on some WAIS subtests, suggests a frequent deficit in spatial capabilities in such subjects. Such results tended to be confirmed by the profiles of the 22 HZ with IQ 20-80. No psychiatric abnormalities were found in HZ, except in one subject with IQ less than 20 which fitted DSM-III-R and ADI criteria for autism. Typical physical manifestations, especially cranio-facial, were more frequently present in the HZ group with lower IQ. Subnormal IQ was probably the most reliable abnormality for the detection of HZ in 49 females at 50% and 25% risk of heterozygosity. PMID- 1897580 TI - Intestinal lymphangiectasia, lymphedema, mental retardation, and typical face: confirmation of the Hennekam syndrome. AB - We report on a male with intestinal lymphangiectasia, mild mental retardation, seizures, and a typical face; the syndrome was first delineated by Hennekam et al., Am. J. Med. Genet. 34:593-600 [1989]. His parents are consanguineous. This case seems to confirm the existence of the Hennekam syndrome. PMID- 1897581 TI - Phenocopy versus genocopy. PMID- 1897582 TI - Noses nobody knows--for real: rhiny and craniorhiny. PMID- 1897583 TI - Adults with Williams syndrome. PMID- 1897584 TI - RN groups seek consensus on who's 'exposure-prone'. PMID- 1897585 TI - No place for a critical care nurse? PMID- 1897586 TI - 'Revealing' finding is no surprise. PMID- 1897587 TI - The postop heart. Case example: myocardial rupture. PMID- 1897589 TI - This hospital patient has Alzheimer's. PMID- 1897588 TI - Tales from public health nursing. True detectives. PMID- 1897590 TI - Weaning from intra-aortic balloon pump support. PMID- 1897591 TI - What triggers a ventilator alarm? PMID- 1897592 TI - Our stories, ourselves: reflecting on practice. PMID- 1897593 TI - A passage through paralysis. PMID- 1897595 TI - Michigan jobfocus. Good opportunities and Great Lakes. PMID- 1897594 TI - Midwest jobfocus. Trends in trauma nursing. PMID- 1897596 TI - Histologic examination of age of the First African Baptist Church adults. AB - This study applies a recently formulated method of histologic estimation of age at death to samples of anterior femoral cortex taken from adult skeletons from the First African Baptist Church cemetery and compares the results with macroscopic age estimates made by J.L. Angel and J.O. Kelley. Of the 65 samples taken, 44 were sufficiently well preserved to produce readable thin sections, although most were so fragile that they had to be embedded before sectioning. In most cases the histologic ages agreed with the macroscopic age estimations within the standard error of the estimate of the histologic method. Most cases of disagreement could be attributed to poor preservation. Despite differences between individual gross and microscopic age estimates, the two methods proved to be significantly correlated and produced the same overall demographic picture of a population whose female members were likely to die at earlier ages than the males. PMID- 1897597 TI - Behavior-induced auditory exostoses in imperial Roman society: evidence from coeval urban and rural communities near Rome. AB - Presence and features of auditory exostoses were investigated in two cranial samples of Roman imperial age (1st-3rd century A.D.). The skeletal material comes from the necropolises of Portus (Isola Sacra) and Lucus Feroniae (Via Capenate), two towns along the Tevere River, in close relation with the social and economic life of Rome. Deep-rooted differences between the human communities represented by the skeletal samples (83 and 71 individuals, respectively, in this study) are documented both historically and archaeologically. The results show lack of exostoses in the female sex, a negligible incidence among the males of Lucus Feroniae, but a high frequency in the male sample from Isola Sacra (31.3%). Auditory exostoses are commonly recognised as localized hyperplastic growths of predominantly acquired origin. Features of the exostoses found in the male crania from Isola Sacra (particularly in relation to the age at death of the affected individuals) support this view. Furthermore, several clinical and anthropological studies have pointed out close links between the occurrence of auditory exostoses and prolonged cold water exposure, generally due to the practice of aquatic sports, or to working activities involving water contact or diving. In this perspective, the differences observed between the two Roman populations and between the sexes (in Isola Sacra) appear to result from different social habits: the middle class population of Portus habitually used thermal baths, whereas it is probable that thermae were seldom frequented (if at all) by the Lucus Feroniae population represented in the necropolis (mostly composed by slaves or freedmen farm laborers).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1897598 TI - Stature in an early mid-19th century poorhouse population: Highland Park, Rochester, New York. AB - If the early 19th century United States was a developing country, then it may be expected that the lowest economic stratum would show some biological consequences of poverty. This report examines that question by estimating stature on 90 male and 64 female adult skeletons from an unmarked cemetery dating between 1826 and 1863. The Highland Park burial ground was adjacent to institutions which interned unfortunates of Rochester, Monroe County, in western New York. The best estimate of male stature (N = 84) is 172.6 cm. A review of other 18th and 19th century height data shows this value not to be relatively stunted, but rather exactly on the predicted mean of its time. If this was a poor population, stunting was not a consequence of poverty. Females (N = 59) showed a best height estimate of 160.0 cm. Less comparative data are available, but this too seems average for the time. A brief discussion of secular trends, changing income inequity and fluctuating stature from the 18th through 20th centuries puts this finding in context. PMID- 1897599 TI - Dimensions of face in Asia in the perspective of geography and prehistory. AB - Data from 24 craniofacial dimensions were compiled for samples representing all the human populations of the world. These were converted into C scores and used to construct Euclidean Distance dendrograms. The populations of the world are best depicted as 8 major regional clusters representing: Africa, Amerind, Asia Mainland, Australo-Melanesia, Eskimo-Siberia, Europe, India, and Jomon-Pacific. The mainland Asian cluster divided into northern and southern components. The Neolithic in both areas is less clearly associated with the northern or southern components and may represent the form of their undifferentiated precursors. This needs to be tested by the addition of further specimens and an adequate sample from South China. Mongols are peripheral members of the Asia-Mainland cluster and should not be thought of as typifying the region as a whole. The use of the term "Mongoloid" is inappropriate in both theory and practice. PMID- 1897600 TI - Skin color variation in eastern Nepal. AB - The purpose of this paper is to provide skin color data on several endogamous groups of eastern Nepal and to demonstrate genetic microdifferentiation in skin color. Skin reflectance measures were taken at the upper inner arm and forehead sites, using the British DSL Model 99 Reflectance Spectrophotometer fitted with blue, green, and red filters. Measurements on 484 males representing six endogamous groups (Jirel, Sunwar, Sherpa, Tamang, Brahman, Chetri) were utilized. After adjusting for group-specific age effects, multivariate likelihood ratio permutation tests were used to assess ethnic differences in skin reflectance means and covariance matrices. Ethnic group membership had a highly significant effect on skin color at the upper inner arm site and at the forehead site. Differential tanning responses among groups were also detected and may represent the influence of genotype-environment interaction on reflectance traits. Mahalanobis distance analysis revealed patterns of microdifferentiation that are inconsistent with oral historical accounts. Little support was found for the ethnohistorical belief that Jirels are a hybrid group descended from Sunwars and Sherpas, even though this scenario is supported by linguistic, anthropometric, and dermatoglyphic data. We suggest that while reflectometric studies of skin pigmentation may be useful in assessing the macrodifferentiation of human populations, the use of skin color in differentiation studies at the local population level needs to be carefully evaluated. PMID- 1897601 TI - Tooth dislocation: the relationship with tooth wear and dental abscesses. AB - Tooth dislocation (tilting) was recorded in 1,200 skulls from 34 museum collections. The findings of dislocation by tooth type, tooth wear, and abscess location are presented. A model for dislocation based upon the progressive loss of tooth support provides a rational explanation for the phenomenon. Physiological continuous tooth eruption was considered to account for a component of the progressive loss of tooth attachment. The process of attrition, pulp perforation, and dental abscess cavity formation resulted in further, more severe loss of tooth support. Heavy functional forces, in association with greatly reduced bone support, tilted the crown lingually and root buccally. When the tooth had tilted to such an extent that the root apices protruded from the bone and, presumably (in life) through the gingival/mucosal tissues, the infected root canals were effectively isolated from the internal environment. The tooth continued to function. The more typical consequence of severe attrition and dental abscess formation was tooth loss; it also isolated an infected tooth from living tissue, but without the benefit of retaining function. PMID- 1897602 TI - On the etiology of interproximal grooves. AB - The recent suggestion by Brown and Molnar (1990) that the common etiology of sinew processing is responsible for the production of interproximal tooth grooves is contested. Based on a review of the Australian evidence and presentation of a previously undescribed dentition from Central Europe, it is argued toothpicks are a likely cause of many artificial grooves in human teeth. PMID- 1897604 TI - Dental microwear in live, wild-trapped Alouatta palliata from Costa Rica. AB - One problem with dental microwear analyses of museum material is that investigators can never be sure of the diets of the animals in question. An obvious solution to this problem is to work with live animals. Recent work with laboratory primates has shown that high resolution dental impressions can be obtained from live animals. The purpose of this study was to use similar methods to begin to document rates and patterns of dental microwear for primates in the wild. Thirty-three Alouatta palliata were captured during the wet season at Hacienda La Pacifica near Canas, Costa Rica. Dental impressions were taken and epoxy casts of the teeth were prepared using the methods of Teaford and Oyen (1989a). Scanning electron micrographs were taken of the left mandibular second molars at magnifications of 200x and 500x. Lower magnification images were used to calculate rates of wear, and higher magnification images were used to measure the size and shape of microwear features. Results indicate that, while basic patterns of dental microwear are similar in museum samples and samples of live, wild-trapped animals of the same species, ecological differences between collection locales may lead to significant intraspecific differences in dental microwear. More importantly, rates of microwear provide the first direct evidence of differences in molar use between monkeys and humans. PMID- 1897603 TI - Continuous tooth eruption in Australian aboriginal skulls. AB - Increases in the distance from the cemento-enamel junction to the alveolar crest (CEJ-AC) have often been attributed to senile atrophy of the bone or to the effects of periodontitis, without reference to the condition of the alveolar crest. This study investigated the relationship between CEJ-AC distance, tooth wear, gender, site of the CEJ-AC measurements, and age in 161 pre-white-contact Australian aboriginal skulls. Individual teeth were included in the study when there was no evidence of dehiscence, periodontitis, or abscess cavity formation in the supporting alveolar bone. The CEJ-AC distances increased as the severity of attrition increased; in male skulls, CEJ-AC distances were greater than in female skulls for all categories of tooth wear. In general, CEJ-AC distances measured on the mesial aspects of teeth were greater than those recorded distally; lingual distances generally exceeded buccal recordings. The best explanation of these findings and similar reports in the anthropological literature is that continuous tooth eruption occurred without the concomitant coronal movement of alveolar bone. This conclusion has significant ramifications for anthropological, epidemiological, and clinical studies which use the CEJ and AC as reference points when measuring periodontal attachment loss (periodontitis). PMID- 1897605 TI - Pressure erosion of the femoral trochlea, patella baja, and altered patellar surfaces. AB - As knee flexion increases, so do tendofemoral and patellofemoral compression forces. Three cases of long-standing uncorrected flexion contractures of the knees are presented that resulted in marked erosion of the femoral trochlea, patella baja, and remodeled patellar articular surfaces likely reflecting increased angles of flexion. It is probable that the deep femoral grooves are the result of adaptation under high-level persistent contact loads from the quadriceps tendon. These examples expand our knowledge of bone remodeling and offer information of potential use in studying ancient skeletal samples. PMID- 1897606 TI - Technical note: calculation of age at formation of radiopaque transverse lines. AB - A simple method for determining the age of an individual at the time of radiopaque transverse (Harris) line formation is presented. To use this method, only two measurements are required: total bone length and distance of line to nearest bone end; these are put into formulae that calculate the percent of total bone growth when the line appeared. The result of this calculation is compared with tables of percent bone growth per year (one to 16 years in females and one to 18 years in males) to arrive at estimations of age at line formation. Since these tables are presented for the femur, tibia, humerus, and radius, this technique can be used on any one of the major long bones exhibiting lines. PMID- 1897607 TI - Is "lingual surface attrition of the maxillary teeth (LSAMAT)" caused by dental erosion? PMID- 1897608 TI - Of hominids, fossils, and cladists. PMID- 1897609 TI - A challenge for psychiatry. PMID- 1897610 TI - Substance abuse disorders: a psychiatric priority. Group for the Advancement of Psychiatry Committee on Alcoholism and the Addictions. AB - The renewed public, governmental, and professional interest in addictive disorders should serve to encourage the interest of psychiatrists in this important and rapidly changing field. It is the view of the Group for the Advancement of Psychiatry (GAP) Committee on Alcoholism and the Addictions that all psychiatrists should possess expertise in the recognition, assessment, and treatment of substance use disorders. This position paper by the GAP committee reviews the role of the psychiatrist in the evaluation and treatment of patients with substance use disorders. It also notes some of the obstacles to full involvement in this field by medical practitioners in general and psychiatrists in particular. The psychiatrist has a critical role to play in the diagnosis and treatment of patients with substance use disorders. As biopsychosocial phenomena, substance abuse problems constitute a special and direct challenge to the psychiatrist, whose training, perspective, and competence should span all three domains. Psychiatrists must be willing to accept this challenge and fully participate in the development and application of treatment strategies adequate to cope with the enormous human suffering resulting from the abuse of alcohol and other psychoactive drugs. PMID- 1897611 TI - Clinical assessment of the risk of violence among psychiatric inpatients. AB - OBJECTIVE: The authors evaluated the reliability and validity of a probabilistic approach to clinical assessment of short-term risk of violence. METHOD: At admission, nurses and physicians independently rated the probability that each of 149 psychiatric patients would physically attack someone during the first week of hospitalization on a university-based locked inpatient unit. Ward behavior was measured with the Overt Aggression Scale. RESULTS: There was a moderate level of agreement between nurses' and physicians' assessments of risk. Ratings of ward behavior showed an increase in the proportion of assaultive patients as the level of estimated risk of violence increased. Although the overall rate of assaults was overpredicted, there was a close correspondence between clinical estimates of patients' chances of becoming violent and the proportion of patients within each risk level who later displayed some type of inpatient aggression. CONCLUSIONS: The reliability and validity of short-term estimates of the risk of violence among acutely disturbed inpatients may be higher than past violence research has suggested. These findings provide preliminary support for the utility of a probabilistic approach to assessment of the risk of violence. PMID- 1897612 TI - High nocturnal body temperature in premenstrual syndrome and late luteal phase dysphoric disorder. AB - OBJECTIVE: Because women with late luteal phase dysphoric disorder (LLPDD) experience symptomatic affective states predictably, they can be studied to determine whether there are biological findings related solely to the clinically symptomatic state. The authors sought to answer the question, Does body temperature change with affective state? METHOD: The core body temperature and motor activity patterns of 10 women with premenstrual syndrome (PMS), six of whom also met criteria for LLPDD, and no other psychological or medical illness were compared to those of six women with chronic, noncyclic dysphoria and six asymptomatic comparison women at four phases of the menstrual cycle. RESULTS: The nocturnal temperatures of the women with PMS/LLPDD were significantly higher than those of the comparison subjects across the entire menstrual cycle, but there were no differences in nocturnal activity levels. The women with noncyclic dysphoria had a mean nocturnal temperature in the follicular phase as high as that of the women with PMS/LLPDD. The temperatures of all women were higher in the luteal phase than in the follicular phase. CONCLUSIONS: These findings suggest that in the future investigators should document menstrual cycle phase in all female subjects and, when studying body temperature, should carefully monitor symptomatic state in comparison subjects. PMID- 1897613 TI - Cognitive outcome following tricyclic and electroconvulsive treatment of major depression in the elderly. AB - OBJECTIVE: This study sought to ascertain the affective and cognitive outcome after tricyclic and electroconvulsive treatment of elderly medical-psychiatric patients meeting diagnostic criteria for major depression, some of whom had normal cognitive functioning and some of whom were cognitively impaired before treatment. METHOD: Patients who met criteria for major depression on the basis of a structured diagnostic interview and who scored 17 or more on the Hamilton Rating Scale for Depression were evaluated with the Mattis Dementia Rating Scale. The patients were then treated in a nonrandom manner with either tricyclic antidepressants or ECT (followed by tricyclic maintenance therapy). The majority of the patients treated with ECT had not responded previously to tricyclics. Follow-up psychometric testing was repeated in 6 months. RESULTS: Among the patients with normal pretreatment cognitive functioning, cognition was generally stable. Among the patients with pretreatment cognitive impairment, a substantial number--including those receiving ECT--demonstrated improvement in cognition. While the majority of patients improved with respect to both their affective and cognitive states, certain treatment-refractory subgroups were nevertheless identified. CONCLUSIONS: The data suggest that cognitive dysfunction associated with depression may improve after treatment in a substantial number of elderly patients, including those receiving ECT. Relapse rates, however, may be relatively high, and residual symptoms may persist, which emphasizes the need for optimal initial and long-term antidepressant strategies for this population. PMID- 1897614 TI - Identification and characterization of greater mood variance in depression. AB - OBJECTIVE: The authors sought to assess the quantity and quality of mood variation in depressed persons. METHOD: Using a visual analogue scale, they compared variation of mood in a group of patients (N = 9) with a DSM-III-R diagnosis of depressive disorder and in a group of nondepressed subjects (N = 9) over 12 consecutive hours. To quantify mood variation for each subject, the authors computed the standard deviation of each subject's 13 mood ratings on the visual analogue scale. To characterize the quality of mood variation within each subject, they plotted each subject's mood ratings as a function of time and applied complex demodulation to confirm cyclical patterns of mood variability (ultradian cycles). RESULTS: The depressed group demonstrated greater mood score variability over the course of the day. Both groups demonstrated ultradian cycles and circadian trends; however, the depressed group demonstrated ultradian cycles of significantly greater amplitude than the nondepressed group. CONCLUSIONS: Repeated assessments of mood at different times of the day may be necessary to obtain an accurate impression of a patient's mood state. Further, the mechanism of depressive disorders may include a deregulation of a normal oscillatory mood variation pattern. PMID- 1897615 TI - Depression through the first year after the death of a spouse. AB - OBJECTIVE: This study assesses the frequency of depressive syndromes during the first 13 months after the death of a spouse. METHOD: Men and women whose spouses had recently died were identified through death certificate records. These subjects completed a multidimensional questionnaire and were interviewed 7-8 weeks (2 months) after the death. Follow-up questionnaires were completed 7 and 13 months after the death. The questionnaires contained specific items corresponding to DSM-III-R criteria for depressive episodes as well as other widely used measures of depressive symptoms such as the Zung Depression Scale and the Hopkins Symptom Checklist. RESULTS: Eighty-four (24%) of 350 widows and widowers met criteria for depressive episodes at 2 months, 72 (23%) of 308 did so at 7 months, and 46 (16%) of 286 did so at 13 months. At each time period, the prevalence was substantially higher than the 4% rate of depressive episodes observed in a comparison group of 126 subjects whose spouses were still living. Widows and widowers most likely to meet criteria for depressive episodes 13 months after the bereavement were younger, had past histories of major depression, were still grieving 2 months after the loss, and met DSM-III-R criteria for depressive episodes 2 and/or 7 months after the death. CONCLUSIONS: Depressive episodes are common after the death of a spouse. Clinicians should maintain a high index of suspicion for the possibility of depression, particularly in young widows and widowers who have a past history of depression or who experience a full depressive syndrome soon after the loss. PMID- 1897616 TI - Predictors of relapse into major depressive disorder in a nonclinical population. AB - OBJECTIVE: This study sought to describe, the natural history of major depressive disorder in a large group of nonclinical subjects. In particular, the analysis determined demographic and clinical risk factors for the recurrence of major depressive disorder. METHOD: Relatives, comparison subjects (matched to relatives for age and sex), and spouses of affectively ill probands underwent structured clinical assessments before and after a 6-year interval. RESULTS: Of 396 individuals who had had only major depressive disorder that ended before the initial evaluation, 33.8% (N = 134) developed a new episode during the 6-year follow-up period. Youth, but not sex, was an important demographic risk factor. The presence of minor depression at the time of initial evaluation and the number of symptoms recalled from the worst previous episode were additional clinical risk factors. At the initial evaluation, 200 other subjects had described a previous history of both major depressive disorder and a nonaffective mental disorder. When compared to the subjects who recalled only a history of major depressive disorder, these subjects were more likely to have been in an episode of chronic intermittent depression at the initial evaluation and to recall a greater number of episodes as well as a greater number of symptoms in the worst episode. A history of a nonaffective mental disorder significantly increased the risk of relapse into major depressive disorder. CONCLUSIONS: These findings agree well with a recent review of clinically based follow-up studies. Thus, youth and a history of nonaffective illness are important risk factors for the recurrence of major affective disorder in a broad variety of settings. PMID- 1897617 TI - Outcome of schizoaffective disorder at two long-term follow-ups: comparisons with outcome of schizophrenia and affective disorders. AB - OBJECTIVE: This research assessed whether the outcome of schizoaffective disorder is more similar to that of schizophrenia or that of affective disorders. METHOD: The authors conducted a prospective follow-up study of 101 schizoaffective, schizophrenic, bipolar manic, and depressed patients assessed at three times: during hospitalization and 2 and 4-5 years later. The follow-up test battery involved detailed assessment of social functioning, work performance, symptoms, posthospital treatment, and rehospitalization. RESULTS: Outcome for schizoaffective patients 4-5 years after hospitalization differed significantly from that for patients with unipolar depression. However, the differences between schizoaffective and bipolar manic patients were more equivocal. Unlike the patients with bipolar disorder, only a limited number of patients with schizoaffective disorder showed complete recovery in all areas throughout the year preceding the 2-year follow-up and the year preceding the 4- to 5-year follow-up. The differences in outcome between schizoaffective and schizophrenic patients were also mixed. These two groups showed some similarities in outcome, but there were fewer schizoaffective than schizophrenic patients with uniformly poor outcome in all areas. CONCLUSIONS: Overall, schizoaffective patients showed some similarities to both schizophrenic and bipolar manic patients. Schizoaffective patients had somewhat better overall posthospital functioning than patients with schizophrenia, somewhat poorer functioning than bipolar manic patients, and significantly poorer functioning than patients with unipolar depression. The data suggest that when mood-incongruent, schizophrenic-like psychotic symptoms are present in the acute phase, they predict considerable difficulty in outcome, even when affective syndromes are also present, as in schizoaffective disorder. It is likely that schizoaffective disorder is not just a simple variety of affective disorder. PMID- 1897618 TI - Psychiatric consultation to a state board of medical examiners. AB - This article describes the evolution of psychiatric consultation to the Oregon Board of Medical Examiners. The board is charged with the licensing and regulation of physicians in the state of Oregon in order to protect the public and uphold the standards of the medical profession. Psychiatric consultation has focused on the board's investigations of physicians with mental illness and/or substance abuse and physicians who inappropriately prescribe psychoactive drugs or sexually abuse patients. Each of these physician groups is described, and remedial programs for each group are discussed. The authors conclude that psychiatric consultation to medical boards is a feasible and productive activity that can make a positive contribution to the lives of a large number of physicians and patients. PMID- 1897619 TI - The comorbidity of borderline personality disorder and other DSM-III-R axis II personality disorders. AB - OBJECTIVE: This study examines the comorbidity of DSM-III-R borderline personality disorder and the other axis II personality disorders. The extent and direction of overlap provides a measure of the clarity of its diagnostic boundaries and descriptive validity. METHOD: In 110 outpatients without concurrent major axis I conditions, axis II diagnoses were assessed in semistructured format and all DSM-III-R personality disorder criteria were rated. Multiple diagnoses were recorded. RESULTS: Twenty-two patients (20%) met criteria for borderline personality disorder; 18 (82%) had at least one additional personality disorder diagnosis. Using measures of frequencies and intercorrelation coefficients, the authors found that overlap was extensive and not confined to any one of the three designated axis II clusters. Factor analysis revealed 1) a group containing borderline personality disorder with paranoid, histrionic, narcissistic, antisocial, and passive-aggressive personality disorders and 2) another grouping of schizoid, schizotypal, avoidant, obsessive compulsive, and self-defeating personality disorders. CONCLUSIONS: Borderline personality disorder appears to constitute a broad, heterogeneous category with unclear boundaries that embraces a general personality disorder concept. Both further refinement of the borderline personality disorder construct and investigation into alternative models to the DSM-III-R axis II classification system are suggested. PMID- 1897621 TI - Psychiatry in eastern Europe today: mental health status, policies, and practices. AB - The author describes the impact of the recent social and political changes in Eastern Europe on psychiatrists and psychiatry. The observations contained in this paper are drawn from his personal experiences as a practicing psychiatrist in East Germany who also served as a member of the Executive Committee of the World Psychiatric Association from 1984 to 1989. The practice of psychiatry in Eastern Europe before the recent social and political changes was highly variable depending on the country, the locale of practice, and the social and political positions of the involved psychiatrists. Adapting to the recent changes will be very difficult, and it will be a long time before the modernization of psychiatric practice in Eastern Europe takes place. Psychiatrists in the Western world can play an important part in the future development of psychiatry in Eastern Europe. Their understanding of the current situation and the historical forces that shaped it is extremely important to the psychiatrists of Eastern Europe. PMID- 1897620 TI - Affective and impulsive personality disorder traits in the relatives of patients with borderline personality disorder. AB - OBJECTIVE: This study tested the hypothesis that the risk for affective and impulsive personality disorder traits commonly found in patients with borderline personality disorder would be greater in the first-degree relatives of probands with borderline personality disorder than in two comparison groups. METHOD: Blind family history interviews were conducted with family informants to assess the extent to which first-degree relatives of 29 probands with borderline personality disorder, 22 probands with other personality disorders who met three or fewer of the criteria for borderline personality disorder, and 43 probands with schizophrenia fulfilled operationalized criteria for the two kinds of personality disorder traits and for other diagnostic categories. The crude proportions of adult relatives with each diagnosis, as well as the age-adjusted morbid risks, were assessed in the three groups of relatives. RESULTS: The risks for affective and impulsive personality disorder traits were independently greater in the 129 relatives of the borderline probands than in the 105 relatives of the probands with other personality disorders and the 218 relatives of the schizophrenic probands. There was no similarly greater risk for any other psychiatric disorder assessed, including major affective disorder. In addition, the relatives of borderline probands with current or past major depressive disorder showed a greater risk for major affective disorders than the relatives of never-depressed probands with other personality disorders but not the relatives of never depressed borderline probands. CONCLUSIONS: These results suggest familial transmission of the hallmark borderline-related personality characteristics and raise the possibility that these familial traits may be partially independent. PMID- 1897622 TI - Safety of short-acting benzodiazepine hypnotics in patients with impaired respiration. PMID- 1897623 TI - Intravenous dexamethasone for symptoms of major depressive disorder. PMID- 1897624 TI - Acute exacerbation of chronic schizophrenia in a patient treated with antituberculosis drugs. PMID- 1897625 TI - Persistent dyskinesia in a patient receiving fluoxetine. PMID- 1897626 TI - Fluoxetine-induced mania in a patient with obsessive-compulsive disorder. PMID- 1897627 TI - Mania induced by fluoxetine in an adolescent patient. PMID- 1897628 TI - Distinguishing borderline patients with splitting. PMID- 1897629 TI - Serum iron and neuroleptic malignant syndrome. PMID- 1897630 TI - EEG abnormalities associated with clozapine treatment. PMID- 1897631 TI - Role of psychoanalytic thought in twentieth-century American psychiatry. PMID- 1897632 TI - Comments on projective identification. PMID- 1897633 TI - Comment on analysis of psychiatric comorbidity in twins. PMID- 1897634 TI - Is life a Wisconsin Card Sorting Test? PMID- 1897635 TI - Religious issues in psychiatry. PMID- 1897636 TI - Hypersensitivity reexamined. PMID- 1897637 TI - Object relations in adolescent girls. PMID- 1897638 TI - Increased risk of stroke in patients with panic attacks: real or perceived? PMID- 1897639 TI - Opiate system in self-injurious behavior. PMID- 1897640 TI - Trauma and dissociation. PMID- 1897641 TI - Credibility of patients in psychiatric research. PMID- 1897642 TI - Water intoxication precipitated by thiazide diuretics in polydipsic psychiatric patients. PMID- 1897643 TI - Managed psychiatric care. PMID- 1897644 TI - Development of DSM-IV. PMID- 1897645 TI - Arthrofibrosis in acute anterior cruciate ligament reconstruction. The effect of timing of reconstruction and rehabilitation. AB - Arthrofibrosis is a potential complication of acute ACL reconstruction. Arthrofibrosis prevents the patient from regaining full range of motion, particularly the terminal 5 degrees of full extension, postoperatively. We did a retrospective study of 169 acute ACL reconstructions in a population of young athletes (average age, 22 years). We sought to determine the optimal time to perform acute ACL reconstruction with respect to arthrofibrosis and the effects of an accelerated versus conventional rehabilitation program. The short-term results were evaluated by range of motion measurements and 13 week Cybex scores. Patients whose ligaments were reconstructed within the 1st week after injury (Group I) had a statistically significant (P less than 0.05) increased incidence of arthrofibrosis (limited extension, scar tissue) over patients who had ACL reconstruction delayed 21 days or more (Group III). At 13 weeks after the reconstruction procedure, Group III patients scored an average of 70% (compared to 51% for Group I, P less than 0.05) on the Cybex evaluation. They also showed a trend toward more flexion of the knee as well as near full extension. Patients who had an ACL reconstruction between 8 and 21 days after injury (Group II) had a similar incidence of arthrofibrosis as Group I when they followed a conventional rehabilitation program postoperatively. However, only a small number of cases (approximately 4%) of Group II patients who followed an accelerated postoperative rehabilitation program had any arthrofibrosis--an observation we also made in the Group III patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1897646 TI - Impact biomechanics of lateral knee bracing. The anterior cruciate ligament. AB - We evaluated the effects of six different prophylactic braces on ACL ligament strain under dynamic valgus loads using a mechanical surrogate limb validated against human cadaveric specimens. Medical collateral ligament and anterior cruciate ligament peak forces, medial collateral ligament and anterior cruciate ligament tension initiation times, and impact safety factors were calculated for both braced and unbraced conditions. These tests were conducted to determine whether or not application of a prophylactic brace might provide protection to the anterior cruciate ligament under valgus loading conditions. The results of this study indicate that those braces that increased impact duration appear to differentially protect the anterior cruciate ligament more than the medial collateral ligament, and that most of the braces tested appear to provide some degree of protection to the anterior cruciate ligament under direct lateral impacts. These findings should be confirmed clinically. PMID- 1897647 TI - Modification of the Bankart reconstruction with a suture anchor. Report of a new technique. AB - We assessed the effectiveness of a new suture anchor that has been designed to anchor sutures into a blind, straight hole drilled in bone. The strength of fixation in glenoid bone is 67 N for the No. 0 anchor and suture, and 82 N for the No. 2 device with suture. During 1988 and 1989, 32 patients underwent a modified Bankart reconstruction for recurrent anterior glenohumeral instability at two centers as part of a prospective study of this modified technique. There were no complications as a result of the technique. The four surgeons involved agreed that the suture anchor simplified the procedure. Seventeen patients have been reviewed, with more than 1 year followup. Ninety-four percent had good to excellent results according to the Bankart rating scale. There was one recurrent dislocation in a football player. PMID- 1897648 TI - The effects of increased tension on healing medical collateral ligaments. AB - The effects of motion and increased levels of stress on the biomechanical, biochemical, and morphological properties of healing medial collateral ligaments were assessed in a rabbit model. In one group, the medial collateral ligament of the left hindlimb was transected and allowed to heal with cage activity for either 6 or 12 weeks. In another group, the transected ligaments were permitted to heal for 4 weeks and then were placed under increased stress by inserting a stainless steel pin perpendicularly underneath the healing medial collateral ligament. The animals were allowed cage activity for an additional 2 or 8 weeks. The varus-valgus joint laxity and the stress-strain properties of the medical collateral ligament substance were obtained. Further, the quantity of total collagen, amount and ratio of the collagen cross-links, dihydroxylysinonorleucine and hydroxylysinonorleucine, and the histologic appearance of the healing medical collateral ligaments were evaluated for all groups. At 6 weeks, knees with a transected medial collateral ligament were twice as lax as the controls. However, joints with the stainless steel tension pin had varus-valgus values approximately 1.5 times those of the controls. At 12 weeks, joints with increased stress were not statistically different from the controls. The group that had healing with increased stress for 12 weeks produced the highest stress for a given strain compared to any other group. Also, the total collagen levels and the ratio of dihydroxylysinonorleucine/hydroxylysinonorleucine were the closest to normal of any transected group. Finally, qualitative histologic improvements were seen, including a more longitudinal arrangement of collagen fibers and decreased cellularity. PMID- 1897649 TI - The axial load teardrop fracture. A biomechanical, clinical and roentgenographic analysis. AB - The anteroinferior cervical vertebral body corner fracture was originally described by Schneider and Cann as the "teardrop" fracture. This report analyzes the biomechanical, clinical, and roentgenographic features of 55 such fractures obtained from the National Football Head and Neck Injury Registry. Teardrop fractures resulting from tackle football characteristically occurred in players attempting to make a tackle in which initial contact was made with the top or crown of the helmet. There were two fracture patterns associated with the anteroinferior corner (teardrop) fracture fragment: 1) the isolated fracture, which is usually not associated with permanent neurologic sequelae; and 2) the three-part, two-plane fracture in which there is an associated sagittal vertebral body fracture as well as fracture of the posterior neural arch. This latter pattern was almost always associated with permanent neurologic sequelae, specifically quadriplegia. Axial loading of the cervical spine was clearly identified as a mechanism of injury for both fracture patterns. Roentgenographic examination must include both anteroposterior and lateral views with computed tomography or tomography as necessary to determine the presence of the sagittal vertebral body fracture and the integrity of the posterior neural arch. PMID- 1897650 TI - Postoperative pulmonary edema in young, athletic adults. AB - Pulmonary edema secondary to postextubation laryngospasm is a potentially life threatening problem, demanding early diagnosis and prompt treatment. We believe that this problem has been grossly underestimated in its incidence, as only seven adults have been reported in the English literature, whereas seven adults have been observed at our institution in only a 24 month period. All were young, healthy, athletic adult males (average weight, 218 pounds) who underwent relatively minor, uncomplicated surgical procedures under general anesthesia. Five of these patients were collegiate and/or professional athletes and had meticulous medical records detailing their clinical course. Clinical laryngospasm was noted immediately following extubation and anesthesia by mask with subsequent pulmonary edema. The diagnoses were confirmed by clinical examination, arterial blood gas determinations or pulse oximetry, and chest roentgenogram. Four adults required reintubation. Six of the seven adults demonstrated very rapid resolution of the pulmonary edema with prompt diagnosis and institution of a therapeutic regimen including oxygen, diuretics, reintubation, and/or positive pressure ventilation. In one patient, the problem was not immediately recognized, and progressed to florid pulmonary edema requiring emergent intubation 14 hours later in the emergency room, and 3 days of mechanical ventilation. The etiology of pulmonary edema following upper airway obstruction represents an interplay between several factors: cardiogenic and neurogenic mechanisms, as well as hypoxia contribute. In this group, excessive negative intrathoracic pressure generated by forced inspiration against a closed glottis is the most likely, consistent, and logical explanation. This study suggests that young, healthy, athletic males may be at increased risk for this complication.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1897651 TI - Soccer injuries among elite female players. AB - Injuries occurring in two female elite soccer teams were recorded during 1 year. Of 41 players, 33 (80%) sustained 78 injuries. The incidence of injury during games was 24/1000 hours, while the incidence during training was 7/1000 hours. The majority (88%) of injuries were localized to the lower extremities, with equal occurrence in the left and right legs. Forty-nine percent of the injuries occurred in the knee or ankle. Most of the injuries were minor (49%), while 36% were moderate and 15% were major. Of the major injuries (N = 12), 10 were due to trauma and 7 (58%) were knee ligament or meniscal tears. Overuse injuries constituted 28% of all injuries and occurred mainly during preseason training and at the beginning and end of the competitive season. Traumatic injuries (72%) occurred mainly during games with a predominance at the beginning of the competitive season. Almost 80% of the traumatic injuries occurred during physical contact with an opponent. Extrinsic factors such as weather, playing surface, temperature, or the position of the player within the team did not influence the injury rate. We conclude that female elite soccer players sustain a high incidence of injury. Few injuries were major, but 17% of the players sustained a major knee injury during the year. PMID- 1897652 TI - Neuropsychologic test performance in amateur boxers. AB - Cognitive functions of 23 amateur boxers were assessed immediately before and after an amateur boxing event. A range of cognitive measures were employed including tasks of verbal, figural, and incidental memory, motor functions, attention and concentration, and information processing speed. Compared to their prefight performance, boxers demonstrated impairments in verbal and incidental memory, but enhanced executive and motor functions postfight. There were no observed differences between winners and losers on any of the measures. The results are compared to other studies that have shown only minor changes in cognitive functions in amateur boxers compared to controls. PMID- 1897653 TI - In vivo measurement of anterior tibial translation using continuous passive motion devices. AB - Early motion protocols following anterior cruciate reconstruction often use continuous passive motion devices. There is concern that these devices may induce undesired anterior translation of the tibia and resulting graft stretching or rupture. This study measured the amount of anterior tibial translation that occurred during one cycle in 10 different brands of continuous passive motion devices. Five patients with ACL deficient knees participated in this study. Anterior translation was recorded by using an electrogoniometer with four degrees of freedom (Knee Signature System). Anterior translation measurements were also recorded for a 20 pound Lachman test in these same five patients using the Knee Signature System. Two of the devices showed anterior translation measurements that approached the recorded 20 pound Lachman values. These two devices had a high calf bar for the primary support of the leg. The results indicate that, when using a continuous passive motion device for early postoperative management of the reconstructed ACL in a patient, use of a calf-supporting type of continuous passive motion could induce an undesired strain of the healing graft. PMID- 1897655 TI - Fluid and electrolyte replacement in the ultramarathon runner. AB - We studied three male runners during three separate ultramarathon races. Serial blood samples were tested for electrolytes, renal function, albumin, calcium, phosphorus, and magnesium. Two runners had aldosterone levels measured during the race and one runner had blood lactate levels measured. All runners ingested an isotonic fluid and electrolyte solution during the race. The runners consumed the solution without medical complications and maintained prerace body weights and hydration levels. Each runner maintained normal endocrine/metabolic parameters. We concluded that it is possible to maintain normal hydration and electrolyte states during a prolonged race, provided that sufficient fluid and electrolyte solutions are ingested. PMID- 1897654 TI - An experimental evaluation of isometric placement for extraarticular reconstructions of the anterior cruciate ligament. AB - We measured the changes in distance between the tibial and femoral attachment points of the extraarticular ACL substitute during knee motion. To measure the changes in distance continuously and directly, a computer-assisted experimental system was developed using an electrolyte-in-rubber transducer. We used 6 cadaveric knees to measure changes in distance of 15 combinations during a simple flexion and extension knee motion. The distance became longer with flexion in each pair of attachment locations. Although the smallest change in distance was obtained between the posterolateral site of the femoral distal metaphysis and a point posterior to the Gerdy tubercle (percent average of the maximum strain was about 12%), it was concluded that the extraarticular ACL reconstruction is not recommended from a standpoint of isometry of the substitute. PMID- 1897656 TI - Stress avulsion fracture of the tarsal navicular. An uncommon sports-related overuse injury. AB - We report nine cases of stress-related avulsion fracture of the tarsal navicular in athletes. This uncommon over-use injury is thought to occur following repetitive cyclic compressive loading secondary to an impingement of the tarsal navicular. The small dorsal triangular fragment is best seen in weightbearing lateral view radiographs and isotope scan and/or tomography help confirm the diagnosis. We feel that operative treatment is the method of choice in highly symptomatic cases and among top athletes because of the shorter recovery time. PMID- 1897658 TI - Partial rupture of the patellar ligament. Results after operative treatment. AB - Partial rupture of the patellar ligament, also known as jumper's knee, is defined as a repetitive overload lesion at the bone-ligament junction at the lower patellar pole. It is found mainly in athletes and is caused either by microruptures or partial macroruptures of the proximal part of the ligament. The abnormal anatomical lesion is focal degeneration, microruptures and macroruptures, and devitalized tissue at the insertion of the patellar ligament. Proliferation and neovascularization are often found, as well as degeneration and incomplete tissue healing. Surgical treatment is indicated only if a prolonged and well-supervised conservative treatment program fails. We operated on 78 patients with jumper's knee, by carefully removing the abnormal tissue from the ligament. At follow-up examination, 71 of 78 patients had excellent or good functional results and complete resumption of sports activities. Objective measurements of thigh muscle strength using a Cybex II dynamometer correlated with the functional results at a low angular velocity. PMID- 1897657 TI - Magnetic resonance imaging of traumatic knee articular cartilage injuries. AB - The purpose of this study was to assess the sensitivity of magnetic resonance imaging in determining the presence of articular cartilage injuries of the knee with arthroscopy as the standard for comparison. Forty-nine articular cartilage lesions were documented in 28 knees (27 patients) by arthroscopy. There were 22 men and 5 women with an average age of 29 years. Multiplanar magnetic resonance imaging was performed with spin echo and gradient-refocused acquisition in a steady state pulse technique. All of the knees had magnetic resonance imaging done within 4 weeks prior to arthroscopy. The magnetic resonance images were interpreted before arthroscopy and interpreted again after the results of arthroscopy were known to better define the potential learning curve for evaluating chondral lesions and to identify the technical limits of the existing imaging protocol/software. For full-thickness articular cartilage lesions, the prearthroscopy sensitivity of magnetic resonance imaging was 41% (12/29) and the postarthroscopy sensitivity was 83% (24/29). For partial-thickness chondral injury, the prearthroscopy sensitivity of magnetic resonance imaging was 15% (3/20) and the postarthroscopy sensitivity was 55% (11/20). The presence of an intraarticular effusion assisted the detection of chondral lesions because of an "arthrogram" effect. As a noninvasive method of evaluating articular cartilage and despite experienced interpretation and the benefit of retrospective analysis, both the prearthroscopy and the postarthroscopy sensitivity of magnetic resonance imaging was low using the imaging parameters described. Injury to articular cartilage is a frequent cause of knee pain and knee surgery; it is important to note at this time that magnetic resonance imaging cannot reliably exclude the presence of an articular cartilage injury. PMID- 1897659 TI - Effectiveness of orthotic shoe inserts in the long-distance runner. AB - Five hundred questionnaires were distributed to long-distance runners who had used, or who were using orthotic shoe inserts for symptomatic relief of lower extremity complaints. Three hundred forty-seven (69.4%) responded (males, 71%; females, 29%). The mean age of the respondents was 36 years (range, 15 to 61). The average distance run per week was 39.6 miles (range, 5 to 98). The mean duration for use of the orthotic inserts was 23 months (range, 1 to 96). The predominant (63%) type of orthotic device used was flexible. The presumed diagnoses in the population studied were excessive pronation (31.1%), leg length discrepancy (13.5%), patellofemoral disorders (12.6%), plantar fasciitis (20.7%), Achilles tendinitis (18.5%), shin splints (7.2%), and miscellaneous (4.9%). Of the runners responding, 262 (75.5%) reported complete resolution or great improvement of their symptoms. Results of treatment with orthotic shoe inserts were independent of the diagnosis or the runner's level of participation. A high degree of overall satisfaction was demonstrated by the finding that 90% of the runners continued to use the orthotic devices even after resolution of their symptoms. Orthotic shoe inserts were most effective in the treatment of symptoms arising from biomechanical abnormalities, such as excessive pronation or leg length discrepancy. Along with other conservative measures, orthotic shoe inserts may allow the athlete to continue participation in running and avoid other treatment modalities that are more costly and time consuming, and therefore less acceptable to them. PMID- 1897660 TI - Neurapraxia of the femoral nerve in a modern dancer. AB - We have presented a case of an acute onset femoral nerve neurapraxia in a pure modern dancer. Repeated mild stretching of the femoral nerve during an established dance routine over a period of several months is implicated as the etiology. The thigh muscles quickly weakened, but regained strength within 3 months. Electromyographic evidence of specific femoral nerve injury initially was negative, but was evident 6 weeks following injury. Overuse syndrome in dancers can cause rapid loss of strength. Other conditions such as herniated intervertebral disc, acute hemorrhage, trauma, iliopsoas rupture, and acute stretching must be ruled out. Complete recovery was the natural outcome. PMID- 1897661 TI - Rupture of the quadriceps tendon after a central third patellar tendon anterior cruciate ligament reconstruction. PMID- 1897663 TI - [Fetal shoulder dystocia]. PMID- 1897662 TI - Isolated avulsion of the popliteus tendon. A case report. AB - We have reported a rare case of an isolated avulsion of the popliteus tendon. In this case the avulsed tendon was associated with a large osteochondral fragment that was easily relocated and fixed anatomically. We believe that the popliteus tendon is important to the mechanics of the knee. We would recommend the treatment as presented in this case should one of these rare cases be encountered. PMID- 1897664 TI - [The role of maternal body in the development of allergic reactivity in a newborn infant]. PMID- 1897666 TI - [Analysis of erroneous prediction of fetal weight based on prenatal ultrasonography]. AB - The study was undertaken to examine 105 cases showing great discrepancies++ between the true fetal mass and that estimated from echographic evidence. Main reasons for high inaccuracies were outlined in predicting fetal mass and possible ways of reducing the frequency of mistakes in estimating fetal mass from prenatal ultrasonographic findings were proposed. PMID- 1897665 TI - [Possibility of predicting intrauterine fetal growth retardation by a single ultrasonic examination (using varying standards)]. AB - The paper deals with early prediction of fetal growth retardation and its severity in a newborn from single ultrasound fetal biometric findings (biparietal head size, chest and belly diameters) at week 20 of pregnancy. The prediction was made by employing the developed varying standards for these parameters as percentile curves and tables. A stepwise prediction of fetal growth retardation was proposed for obstetric in- and outpatient settings, which was presented as an IBM personal computer dialogue program. The positive diagnostic value of fetal growth retardation prediction was found to be 69.7%, its negative value was 86.9%. The paper discusses whether therapeutic measures and pregnancy length affect the efficiency of its prediction and stresses that the prediction is valuable for individual well-grounded tactics for pregnancy management. PMID- 1897667 TI - [Prenatal ultrasonographic diagnosis of congenital isolated developmental defects of fetal extremities]. AB - The paper shows that echography can be used in the diagnosis of most congenital fetal limb developmental defects. The detection accuracy for severe anatomic defects was 83.3%. That for mild hand and foot developmental defects was achieved in 54.8% of the cases. Bilateral coxofemoral joint dislocation was diagnosed only in 2 fetuses. The paper also presents echograms of most malformations detected and emphasizes that it is essential to make a comprehensive and detailed examination of all fetal limbs. PMID- 1897668 TI - [Possibilities and prospects of fetal Doppler echocardiography]. PMID- 1897669 TI - [Dynamics of forward fetal movement during labor and its graphic interpretation]. AB - The paper provides echographic++ findings of dynamics of fetal forward movement along the reproductive tract from 88 parturients. It has been found that displacement of the placenta previa was recorded by echography++ when the cervix uteri was 3'36 cm dilated and this continued in accordance with the type revealed (ascending, stepwise, or wave-like). The graphs of fetal head displacement were generally similar to those of increased dilatation of the uterine orifice. Possible biological mechanisms that regulate the coupling of the two processes during labour are also considered in the paper. PMID- 1897670 TI - [Current diagnostic methods and therapeutic principles in various forms of puerperal endometritis]. AB - A total of 55 puerperants+ with endometritis followed by spontaneous labours (26 females) and cesarean operation (29 females) were studied. A comprehensive study involved echography, hysteroscopy, bacteriological analysis of the uterine content, and histological examination of mucosal curettage of the corpus uteri. Three types of the clinical course of endometritis were identified: 1) in the presence of placental tissue residues; 2) with necrosis of delayed decidual tissue and lochia- or hematometra; and 3) a "pure" type of endometritis without abnormal tissues in the uterus. Uterine curettage was performed in the first type of endometritis, vacuum aspiration of its content was carried out in Type 2. The patients from Group 3 who had the most severe inflammatory process of the uterus underwent its cavity washing with large volumes of cold antiseptic solutions, took detoxifying, ++rheo-vasoactive and protein agents, received immunomodulating and uterotonic therapy. The algorithm developed for management of puerperants+ with postpartum endometritis substantially enhanced the efficiency of therapy and prevented severe septic events in time. PMID- 1897671 TI - [Dynamics of lysozyme levels in the blood serum and milk of puerperae with various functional activities of the breasts]. AB - The morbidity rates, ++features of lactation formation, and serum and breast milk lysozyme levels were studied in 91 parturients who showed various breast functional activity in the early postpartum period. The highest frequency of postpartum ++pyo-septic diseases was found in females with hyperlactation. There was earlier appearance of foremilk and milk in these females. Healthy mothers with higher breast functional activity exhibited the greatest levels of lysozyme in the milk and marked decreases in its levels in the blood within the first 3 days as compared to those observed in females who had normal or insufficient quantities of milk. PMID- 1897672 TI - [State of the breasts in patients with hyperprolactinemia-induced amenorrhea and the effect of the treatment with parlodel]. AB - The mammary glands were examined in 36 patients with +Hyperprolactinemia-induced amenorrhea. ++Fibro-adipose transformation (33.3%), involutional changes unassociated with age (30.6%), the hyperplastic processes fibrocystic mastopathy, adenosis (36.1%) were found to be equally encountered in the pattern of breast alterations. Parlodel therapy given to patients with ++Hyperprolactinemia-induced amenorrhea not only recovers menstrual and reproductive functions, but exerts a favourable action on the mammary glands, promoting the restoration of glandular tissue and the decrease in deformity of a stromal component. PMID- 1897673 TI - [Uretero-vesicovaginal fistula]. AB - The paper outlines the problems in the diagnosis and treatment of associated ++uretero-vesicovaginal fistulas on the basis of a follow-up of 72 patients. The most informative diagnostic methods and effective operative techniques are proposed. PMID- 1897674 TI - [Evaluation of risk factors of developing underlying and precancerous diseases of the uterine cervix]. AB - The paper analyzes risk factors for underlying and precancerous processes of the cervix uteri in females. The application of a mathematical instrument and computers made it possible to define the most significant risk factors and to evaluate the degree of their impact. The findings may be used in the program test in performing mass prophylactic surveys to identify a group of females who are at a high risk and require a more detailed examination. PMID- 1897676 TI - [Characteristics of surgical treatment of pathologic conditions of the cervical stump]. AB - The paper gives the results of surgical management in 65 patients with cervical stump diseases. According to the pattern of the disease, 4 groups of patients were identified: 1) those with inflammatory diseases, 2) those with endometriosis, 3) those with myoma, and 4) those with prolapse of the cervical stump. Low-quality and inadequate suture material was found to be a cause of inflammatory diseases of the cervical stump. It is concluded that it is not expedient to use capron, lavsan, and silk to suture the cervical stump during supravaginal amputation of the uterus. Catgut, vicryl, debone were shown to be an optimal suture material. The practice of surgical management of patients with inflammatory diseases, endometriosis, cervical stump myoma and prolapse indicates that it is advisable to extend indications for uterine extirpation. PMID- 1897675 TI - [Clinical significance of analysis of estrogen and progesterone receptors in human uterine tissues]. AB - The action of steroid hormones in the target cell was found to be associated with the presence of specific receptors in the cytoplasm. Uterine, endometrial, and myometrial tissues obtained at hysterectomy for endometrial carcinomatosis and fibromyomas were used. In fibromyomas, the estrogen and progesterone receptors were found to be higher in the cytosol than in the normal myometrium. In endometrial carcinomatosis, the estrogen receptors were in varying quantities: normal, low, or nil in the cytosol, whereas the progesterone receptors were low or nil. PMID- 1897677 TI - [Prenatal ultrasonographic diagnosis of prosencephaly]. PMID- 1897678 TI - [Experimental study of the effects of fenibut and seduxen on fetal development in the last third of pregnancy]. PMID- 1897679 TI - [Local vaginal thermometry in inflammatory diseases of the uterus and its adnexa]. PMID- 1897680 TI - [Pharmacological stimulation of acupuncture points for analgesia in patients with gynecologic diseases in the postoperative period]. PMID- 1897682 TI - [Diagnosis and treatment of amenorrhea in adolescents caused by weight loss]. PMID- 1897681 TI - [Diagnostic and prognostic value of immunological studies in women with inflammatory processes in the adnexa uteri]. PMID- 1897683 TI - [Use of diuretics in pregnancy]. PMID- 1897684 TI - Effect of cigarette smoking on the humoral immune response in pigeon fanciers. AB - Tobacco smoking is associated with increased prevalence of various diseases. In this study, we have used an indirect enzyme-linked immunosorbent assay (ELISA) to investigate the specific IgG response to pigeon serum and its relationship to tobacco smoking. In a large group of pigeon fanciers the development of pigeon breeder's disease and some of the clinical features were also investigated. We found a sensitization rate of 31.9%, a lower degree than that found by other authors, in spite of using a less specific antigen. We also found that fanciers who are current cigarette smokers had significantly lower levels of IgG antibody to pigeon serum (P less than 0.001). Finally, 11.9% of the population had chronic bronchitis as their only manifestation of possible pigeon-related disease. 19.6% of the sensitized fanciers had chronic bronchitis, were non-smokers and had no other risk factor for developing chronic bronchitis. PMID- 1897685 TI - In vitro screening for inhalant allergy with multi SX 1 RAST (Phadiatop). AB - A new in vitro screening test for inhalant allergy (Phadiatop, Pharmacia Uppsala, Sweden) was evaluated for its effectiveness in identifying allergic patients. The test is based on the radio-allergo-sorbent-test (RAST). Specific IgE antibodies to different inhalant allergens are detected simultaneously. Serum samples from 300 patients and controls were run with Phadiatop. 96% of 150 patients with proved allergic disease were correctly identified by Phadiatop. 92% of 150 individuals without clinically relevant allergic hypersensitivity were found correctly to be negative. Allergic disease was proved or excluded by case history, skin prick test, RAST and, in some cases, additionally by provocation challenge. PMID- 1897686 TI - Clinical characteristics of patients with repeated systemic reactions during specific immunotherapy with hymenoptera venoms. A retrospective study. AB - In general, specific immunotherapy with hymenoptera venoms can be considered as safe, but occasionally there are patients who cannot reach the maintenance dose due to repeated systemic reactions (RSR) or who suffer from RSR during maintenance therapy. In a multicenter retrospective study comprising seven departments in Germany, Austria and Switzerland 23 patients with RSR were reported from approximately 3000 patients treated with hymenoptera venoms (bee and wasp venom to approximately equivalent frequency). From these, 22 were allergic to bee venom and only one to vespid venom. In general the clinical symptoms of RSR were milder than the initial reaction. But 4/23 (18%) exhibited cardiovascular reactions up to full shock. Neither anamnestic details, reactivity in skin tests or in vitro tests revealed a special pattern of patients with RSR. In some patients, however, an extremely high reactivity in the skin test was found and may indicate the possibility of further RSR. PMID- 1897687 TI - Increased chemokinetic and chemotactic responses of eosinophils in asthmatic patients. AB - The aim of the present study was to investigate the migratory responses of eosinophil and neutrophil granulocytes from asthmatic patients compared with granulocytes from healthy individuals. Twenty-three patients with unstable and severe asthma and blood eosinophilia (greater than 400 x 10(6) cells/l) were selected for the study. Eosinophil and neutrophil chemotactic and chemokinetic responses were tested twice, at the beginning and end of a 5 week treatment period. Lung function was followed by daily measurements of PEF. The eosinophils of the asthmatics demonstrated increased chemokinetic responses to albumin, autologous serum, and normal human serum (NHS), and an increased chemotactic response to NHS at the beginning of the treatment period compared with eosinophils from the references. At the end of the period the eosinophil chemokinetic responses to albumin, autologous serum and NHS were still increased and so was the chemotactic response to zymosan-activated serum (ZAS). The neutrophil migratory responses were not increased compared with those of the references, except for the chemokinetic response to autologous serum, which was increased both at the beginning and end of the treatment period. Patients in whom the eosinophil migratory responses, to most of the agents used, decreased over the treatment period, demonstrated a significantly greater improvement of their lung function at the end of the period compared with patients in whom the eosinophil migratory responses increased. However, no direct relationship between eosinophil migratory responses and lung function of the patients was found. In conclusion, the present investigation demonstrated increased migratory responses of eosinophils from asthmatic patients. This enhanced responsiveness is proposed to be due to priming of the eosinophils in vivo, and might be one mechanism behind the selective recruitment of eosinophils to the lungs of asthmatics. PMID- 1897688 TI - Reversal and prevention of airway response to antigen challenge by the inhaled leukotriene D4 antagonist (L-648,051) in patients with atopic asthma. AB - We examined the ability of the inhaled leukotriene D4 antagonist (L-648,051) to inhibit antigen-induced asthmatic responses. Twelve patients with stable exogenous asthma participated in two separate double-blind, placebo-controlled, cross-over trials. The ability of the antagonist to reverse or inhibit antigen induced bronchoconstrictor response was examined; both the immediate and the late phases were studied. In the reversal study, patients inhaled 800 micrograms of L 648,051 during the immediate phase (15 min after antigen challenge) and again during in the late phase (7 h after antigen challenge). In the prevention study, the same dose (800 micrograms) of L-648,051 was inhaled before the expected immediate reaction (5 min before antigen challenge) as well as before the expected late reaction (2.5 h after antigen challenge). The LTD4 antagonist was not effective in reversing the airway response to inhaled antigen, as measured by airway resistance (Rt), forced expiratory volume in 1 s (FEV1) or forced vital capacity (FVC). When the antagonist was given prior to antigen challenge, a slight reduction in Rt was observed during the immediate phase, but not during the late phase. Some improvement in FEV1 and FVC during the immediate phase was also observed, but these changes did not reach statistical significance. These results suggest that LTD4 plays a role in the immediate phase of antigen-induced asthma. PMID- 1897689 TI - Occupational asthma in bakeries caused by sensitivity to alpha-amylase. AB - We report on a patient with asthma induced by occupational exposure to alpha amylase derived from Aspergillus oryzae, which is a component of bread additives. A type I hypersensitivity to this enzyme was demonstrated by means of skin test, immunoassay for specific IgE, and immediate bronchial provocation test response to an alpha-amylase extract. PMID- 1897690 TI - Comparison of antigenic and allergenic components of Holoptelea integrifolia pollen collected from different source materials. AB - Antigenic extracts prepared from pollen samples collected at weekly intervals during the same season did not exhibit significant variation in protein concentration. Stored pollen samples from different years, however, showed highly significant variations in protein concentration. The protein content of samples from different ecozones of India also varied (CV = +/- 32%). The IEF and SDS-PAGE patterns were almost identical in samples from the same season, but were variable in the samples stored from different years and different parts of India. IgE binding proteins from different samples also varied depending on the overall protein profiles. Almost all the patients, however, showed IgE binding to four proteins at 50, 60, 66 and 70 kD, indicating the important allergenic components of Holoptelea integrifolia. PMID- 1897691 TI - Allergen-containing immune complexes used for immunotherapy of allergic asthma. II. IgE and IgG immune response during and after hyposensitization of sensitized guinea pigs. AB - In a previous study guinea pigs inbred for their ability to develop respiratory anaphylaxis to experimental antigens have been used for comparison of different forms of immunotherapy (IT). Passive, active and combined (immune complexes prepared from antigen and specific IgG) IT was compared with placebo. In the present study methods were evaluated for determination of the allergen-specific IgE and IgG. IgE was determined by the passive cutaneous anaphylactic test (PCA) and the variability of this test on different strains of the recipient guinea pig was investigated. The same strain as used for the IT study was found to produce the most potent response. Radioimmunometric assays (RIA) were developed and validated for determination of specific IgG1 and IgG2. The IgE and IgG immune response in animals from the IT study were then evaluated by means of PCA and RIA. Animals from all four treatment groups were sensitized during the first part of the IT study, and responded with a marked IgE synthesis which later stabilized on a more moderate level. In spite of notably reduced symptoms in groups treated with active and combined IT, no difference in the IgE level was found between the four groups. In contrast to IgE, mean group titers of IgG1 and IgG2 in the groups receiving active or combined IT rose drastically during the first part of therapy and closely paralleled the clinical response during the rest of the study period. However, in the individual animals, no correlations were found between immune response and clinical symptoms. Thus, the strong IgG response during immunotherapy may not be causally related to the outcome of treatment. PMID- 1897692 TI - Cyclosporin for steroid-dependent asthma. AB - We used cyclosporin to treat 12 adult patients with severe bronchial asthma who had been on systemic steroids for an average of 16 years. During the baseline period, lasting 4-6 months, therapy with high doses of inhaled beclamethasone, aminophylline and salbutamol was standardized and a minimum necessary dose of systemic steroids was established. After 9 months' treatment with low-dose cyclosporin (average whole-blood trough levels of 105 ng/ml), in six patients the daily dose of oral prednisone could be reduced from mean 30 mg to mean 11 mg, while daily symptom scores and peak expiratory flows improved significantly. This was accompanied by a reduction in exacerbations of asthma. However, in six other patients attempts to taper the steroid doses were unsuccessful, and cyclosporin was stopped after 4 to 7 months. These preliminary results suggest that cyclosporin might be of benefit in some patients with steroid-dependent asthma. PMID- 1897693 TI - Occupational rhinitis and asthma caused by inhalation of Balfourodendron riedelianum (Pau Marfim) wood dust. AB - The case of a 30-year-old wood-worker, with rhinitis and asthma induced by exposure to the dust of Pau Marfim wood (Balfourodendron riedelianum) is reported. Hypersensitivity to this wood was confirmed by positive skin test, bronchial challenge test and RAST. The bronchial response was inhibited by sodium cromoglycate. Unexposed persons did not exhibit reactivity to this wood in any of the tests. When electrophoretic analysis of proteins in polyacrylamide gel was applied to a crude (phosphate-buffered) extract, an homogeneous distribution of low MW material was detected, with no clearly defined bands, suggesting the presence of filamentous type proteins. To the best of the author's knowledge, this is the first reported case of occupational rhinitis and asthma due to Pau Marfim wood dust. A type I (IgE-mediated) hypersensitivity mechanism was demonstrated but the non-glomerular nature of the proteins precluded further identification of the antigens involved. PMID- 1897694 TI - The antigenicity of house dust mites. PMID- 1897695 TI - Epidemiology of house dust mite allergy. PMID- 1897696 TI - Diagnosis of house dust mite allergy. AB - The medical history may be conclusively descriptive in house dust mite allergy in patients with asthma and rhinoconjunctivitis. Often the patients have both diseases. Sensibilization to D. pteronyssinus and D. farinae can be demonstrated by skin prick testing. If the diagnosis is still doubtful, the next step will be to perform a RAST test or a histamine release test. It is also important to investigate for mite exposure at the patient's residence, if the patient is suspected to be mite-allergic. Allergen challenge test in the shock organ should be performed, if hyposensitization is considered, or if, in a few cases, the mite diagnosis is still doubtful. PMID- 1897697 TI - Diagnostic procedures--exposure and environment. PMID- 1897699 TI - House dust mite allergy and anti-mite measures in the indoor environment. PMID- 1897698 TI - Treatment of patients allergic to house dust mites. PMID- 1897700 TI - Social, political, economic and health consequences of environmental treatment of house dust mites. PMID- 1897701 TI - The biology of mites. PMID- 1897702 TI - [2 cases of adenocarcinoma of nasal cavities and paranasal sinuses]. AB - Malignant tumors of the paranasal sinuses are relatively rare. Generally squamous cell carcinoma appear to be dominant. Adenocarcinoma make up 12 to 15 percent of all nasal and paranasal sinus malignancies. Adenocarcinomas are most often seen in the middle turbinate and ethmoid sinus. We report 2 cases and discuss its clinical findings, the treatment and possible etiologies. PMID- 1897703 TI - [Ambulatory aerosol therapy in the treatment of chronic pathology of the O.R.L. region]. AB - This study considers the efficacity of the ambulatory aerosol therapy in chronic cases of the ENT area. A nebulizer, air-jet type, of 4 microns MMAD, was the device employed, and an ample spectre antibiotic (cefotaxime) a mucolytic (N acetyl-cysteine) plus a corticoid (methyl-prednisolone) the associated drugs. The antibiotic was discarded when otitis were the problem. The results have been favourable in 75 percent of the cases whilst negative in the resting 24 percent of the treated subjects. PMID- 1897704 TI - [Extreme stapedectomy]. AB - Extreme stapedectomy is an operation aimed at restoring a serviceable hearing in patients affected by far-advanced otosclerosis with profound hearing loss. Surgery is performed on the understanding that the hearing aid will still be needed after the operation. Therefore, patient's expectations should be confined to possibly improved performance with a hearing aid as a consequence of the operation. Clinical as well as audiological preoperative assessment must be very rigorous. Counselling is mandatory and a trial period with a hearing aid is strongly advisable. Our experience is based on 15 cases, operated on between 1984 and 1988. A small fenestra technique was performed using wire-teflon piston prostheses. Results were satisfactory and in accordance with the ratio of the procedure in 8 cases (53%). 7 patients (47%) yielded an unsuccessful outcome and 2 of them had a dead ear (13%). This high rate of labyrinthine failure, the improvement in hearing aids and cochlear implants technologies well are likely to reduce the number of potential candidates for an extreme stapedectomy. However, this operation should be still kept in the otologist's armamentarium as a possible option in borderline cases. PMID- 1897705 TI - [Choanal atresia: review of embryology and pathogenesis]. AB - In the paper a study on the embryology and pathogeny of choanal atresia is presented, with particular reference to its association with other congenital malformations. The experience of the AA., gained through 10 of those cases seen at the ENT-department of the Servasa Hospital, Alicante, is the low incidence of coexisting malformations. They emphasize one case of familiar presentation (mother-daughter), other with eye coloboma and bifid uvula coexistence and a last one with a sensorineural deafness of moderate degree. PMID- 1897706 TI - [Clinical diagnosis of choanal atresia]. PMID- 1897707 TI - [Surgical correction of choanal atresia. Our personal experience]. AB - We find that the treatment indicated for bilateral choanal atresia in the newborn is the transnasal approach, maintaining the patency by means of soft tubes (endotracheal) through 5-7 weeks. The few which recurred were managed by the transpalatal technique. The AA. describe their own experience in 10 cases seen at the ENT-department of the Servasa Hospital, Alicante, between 1979-1989. PMID- 1897709 TI - [Syndrome of multiple nevoid basal cell carcinoma]. AB - The paramount features of the multiple nevoid basal Carcinoma, the so-called Gorlin's syndrome, are the presence of multiple maxillary cysts (odontogenic keratocysts), several nevoid basal cells carcinomata and some skeletal anomalies. Since its first description, due to Jarish (1894), at least about 250 cases have been published. The odontogenic keratocysts present themselves with ENT symptoms, specially when arising on the upper maxillary bone or on the homonymous sinus. Owing to this reason, the AA. of the paper, recall the clinic aspects of the condition. PMID- 1897708 TI - [Adenolymphoma or Warthin's tumor: review of 30 cases]. AB - Perusal of Warthin's tumors treated during the past 20 years (1969-1989) in our Hospital department. As a whole 229 tumors of salivary glands were operated upon, 30 of them being adenolymphomata. The parameters of our series were confronted with those given by the cases of the literature. In the paper are also reminded the several theories concerning the origin of this tumor. PMID- 1897710 TI - [Brown tumor of the maxilla as initial manifestation of primary hyperparathyroidism]. AB - The paper reports the case of a maxillary brown tumor as early sign of primary hyperparathyroidism. Brown tumors are very unusual growths in daily ENT practice and an odd start of primary hyperparathyroidism. The AA. emphasize the importance of a correct differential diagnosis, especially with those tumors showing multinucleated giant cells (osteoclast type)--such as true giant cells tumor and central giant granuloma--prior to its management. They also comment on the interesting contribution to diagnosis by imagery brought by CT scan, magnetic resonance (MR), ultrasonography (echography) and digital subtraction gammagraphy to attain the topographic site of the parathyroid tumor. PMID- 1897711 TI - [Osteoma of the mastoid]. AB - Report of a large ivory-like Osteoma of the mastoid surgically removed. Some pathological, clinic and therapeutic considerations about the subject are added. PMID- 1897712 TI - A clinical study of vestibular neuronitis. AB - By means of clinical and neurotological findings in 38 patients with vestibular Neuronitis, an analysis of the clinical-pathological manifestations, that may be included into this denomination, has been carried out. The probable etiology of this disease and the results of the tests performed have also been analyzed. In the light of these results the vestibular compensatory mechanisms, studied with later periodic tests, are discussed, and the conclusions on the prognosis and treatment of this entity derived. PMID- 1897713 TI - [Insertion of dental implants in the Highmore antrum. Improvement of the maxillary sinus base by bone meal and Tissucol]. AB - After five years of experience and good results, the A. introduces a new method for inserting dental implants into the upper jaw. In the majority of cases fails the insertion of the implant in this area, because of the thinness of the bony ring between the alveolar crest and the base of the sinus, resulting in defective fixation. The fixation of the implant is made, after the elevation of the mucosa of the alveolar recess (whether normal or pathological) with a mixture of bone meal and "Tissucol". This compound (pate) wraps the implant, previously set in place by the dentist. In cases of maxillary sinus surgery, the A. recommends, once the mucosa has been treated, to fill the alveolar recess with this paste moulded as a sloping surface running from the outer wall of the sinus toward the floor of the nose, both cavities communicating through the due counter-opening. PMID- 1897714 TI - [Clinical aspects and diagnosis of expansive processes in the cerebellopontine angle]. AB - The AA. present a review of the expansive processes of the cerebellopontine angle (CPA) diagnosed at their Department, during the six last years. Emphasis is made upon the clinic findings gained through neuro-otological explorations and imaging, both helpful for preoperative diagnosis of the nature of the tumor. PMID- 1897715 TI - [Prognostic value of tubo-tympanic mucociliary clearance in surgery of chronic otitis media]. AB - The AA. have studied a group of 52 patients affected of C.M.O. (with central perforation) which underwent reconstructive surgery of the middle ear. The time of the tubo-tympanic mucociliary clearance, tried by means of a saccharin solution, was correlated with the surgical outcome. The conclusion drawn out is the success of reconstruction when the mucociliary system works well. PMID- 1897716 TI - [Laryngeal rhabdomyoma]. AB - Adults Rhabdomyoma are benign and rare tumors of skeletal muscle. The bibliography gathers about 60 cases, sitting on the head and the neck (95%), specially on the floor of the mouth, larynx or pharynx. Two exceptional case has been reported, one in the abdominal wall, the other on the retroperitoneal space, the latter being a mixed rhabdomyoma (either foetal and adult). Although the condition shows typical morphological features, the interest of the case reported, rely, apart of its scant presentation, on the possibility of leading to a mistaken clinic-macroscopic diagnosis of malignant mesenchymal tumor, because of its outward appearance. PMID- 1897717 TI - [Adenopathy caused by Listeria monocytogenes]. AB - Human infection by Listeria Monocytogenes has been considered a rare disease in adults, usually associated to immunosuppressed patients. Meningitis is the main clinical manifestation. Sepsis, endocarditis, peritonitis and circumscribed abscesses are occasionally found. PMID- 1897718 TI - [Pre-epiglottic cysts]. PMID- 1897719 TI - Structural characterization of protein tryptic peptides via liquid chromatography/mass spectrometry and collision-induced dissociation of their doubly charged molecular ions. AB - The formation of multiply charged molecular ions via the field-assisted ion evaporation mechanism during electrospray ionization enables the use of an atmospheric pressure ionization quadrupole mass spectrometer system for characterizing biologically important peptides. The straightforward implementation of high-performance liquid chromatography (HPLC) into this new strategy to determine the molecular weight of tryptic peptides via the pneumatically assisted electrospray (ion spray) interface is presented. Examples utilizing both microbore (1.0 mm) and standard bore (4.6 mm) inside diameter columns are shown for the LC/MS molecular weight determination of tryptic peptides in methionyl-human growth hormone (met-hGH). Injected levels from 50 to 75 pmol of tryptic digest onto 1 mm i.d. HPLC columns provided full-scan LC/MS or LC/MS/MS results without postcolumn splitting of the effluent. When standard 4.6 mm i.d. HPLC columns were used, a 20:1 postcolumn split was utilized, which required from 1 to 5 nmol of injected tryptic digest for full-scan LC/MS or LC/MS/MS results. Collision-induced dissociation (CID) mass spectra resulting from either "infusion" or on-line LC/MS/MS analysis of the abundant doubly charged ions that predominate for tryptic peptides under electrospray conditions provided structurally useful sequence information for met-hGH and human hemoglobin tryptic digests. The slower mass spectrometer scan rate used during infusion of sample provides more accurate mass assignments than on-line LC/MS or LC/MS/MS, but the latter on-line experiments preclude ambiguities caused by matrix or component interferences. However, in some instances very weak CID product ions preclude complete tryptic peptide structural characterization based upon the CID data alone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1897721 TI - Microwave acid digestion and preconcentration neutron activation analysis of biological and diet samples for iodine. AB - A simple preconcentration neutron activation analysis (PNAA) method has been developed for the determination of low levels of iodine in biological and nutritional materials. The method involves dissolution of the samples by microwave digestion in the presence of acids in closed Teflon bombs and preconcentration of total iodine, after reduction to iodide with hydrazine sulfate, by coprecipitation with bismuth sulfide. The effects of different factors such as acidity, time for complete precipitation, and concentrations of bismuth, sulfide, and diverse ions on the quantitative recovery of iodide have been studied. The absolute detection limit of the PNAA method is 5 ng of iodine. Precision of measurement, expressed in terms of relative standard deviation, is about 5% at 100 ppb and 10% at 20 ppb levels of iodine. The PNAA method has been applied to several biological reference materials and total diet samples. PMID- 1897720 TI - Scanning electrochemical microscopy: theory and application of the transient (chronoamperometric) SECM response. AB - A study of the transient (chronoamperometric) response of the scanning electrochemical microscope (SECM) is presented. SECM transients were simulated digitally with a novel integrator based on a Krylov algorithm. The transients observed with planar electrodes (PE), microdisks (MD), and thin-layer cells (TLC) are shown to be limiting cases that fit the simulated SECM transients at very short, intermediate, and long times, respectively. A procedure is established that, provided the tip radius is known, allows the determination of the diffusion coefficient of the species in solution independent of its concentration and the number of electrons transferred in the electrode reaction. Experimental SECM transients are reported for the electrochemical oxidation of Fe(CN)6(4-) in KCl; the diffusion coefficient of Fe(CN)6(4-) was found to agree very well with the literature value. PMID- 1897722 TI - Sensitized room-temperature luminescence in reverse micelles using lanthanide counterions as acceptors. AB - The analytical usefulness of sensitized room-temperature luminescence in reverse micelles using lanthanide counterions is examined. The technique is based on the unique luminescent properties of tripositive lanthanide metal ions as counterions for the surfactant and the molecular organization produced by reverse micelles. After excitation, the analyte molecule transfers its triplet-state energy to an acceptor molecule (lanthanide), which subsequently emits luminescence. Two surfactants with different lanthanide counterions have been synthesized and characterized by spectroscopic and mass spectrometric techniques. When compared to the lanthanide salt, the sensitized luminescence of the lanthanide surfactant is substantially enhanced. The exact locations of the analyte and the counterion in the micellar system are discussed. The efficiencies of energy transfer for the two surfactants are compared. PMID- 1897723 TI - Tracing aerosol pollutants with rare earth isotopes. PMID- 1897724 TI - Elements of a general theory of joints. 4. Coupled joints as simple gear systems. AB - In the present article the relative motion in the horizontal plane of 2 adjacent lumbar vertebrae (axial rotation of the lumbar spine) and the cranial border movement of the mandible parallel to the vertical-sagittal plane are examined. The interplay of joints is depicted onto the function of a gear system with positive drive. The limits of this projection are described. PMID- 1897725 TI - [The construction principle of bone. II. Microstructure]. AB - On the basis of the ultrastructure of the Haversian lamellar system of bones analyses from the biomechanical viewpoint were undertaken. Instead of computed results preference was given to comparisons with tubes, fibres and nets so as to demonstrate clearly the building principle and movement phenomena. From the course of the collagenous fibres the tensile strains could be discerned which facilitated to determine also the direction of the compressive strains. The mineral components of the bone tissue are oriented toward the direction of the compressive strains. The construction principle of the lamella, however, facilitates reversible deformations and thus regeneration processes which distinguishes it from other technical building principles. PMID- 1897726 TI - [Lymphaticovenous communication in the mammary gland of the female dog]. AB - Lymphaticovenous Communications were searched in the mammary glands of 24 bitches. Injections of indian ink into the interstice of living animals were followed after death by the filling of the veins with latex and barium sulphate. Afterwards, the used techniques were: microdissection, angiography, clarification and histological section. The results obtained would seem to prove the existence of Lymphovenous Anastomoses. The roles of these communications in the canine mammary gland neoplasia are discussed. PMID- 1897727 TI - [Structure of the rete testis of the cat (Felis domestica, L)]. AB - The rete testis of the cat consists of 3 parts: a septal or interlobular part; a mediastinal part and a tunical part. The septal part contains the septal or transitory tubuli recti and the tubuli recti. The transitory tubules are formed as a confluence of the seminiferous tubules at the apex of the testicular lobules and the tubuli recti. The mediastinal rete is formed of long, straight channels which increase in size and become more irregular and anastomotic below the tunica albuginea at the cranial extremity of the testis. The end is characterized as the tunical part of the rete testis and communicates with the extratesticular rete testis. The channels all parts of the rete are lined by simple cuboidal or columnar epithelium. These epithelial channels are supported by a connective tissue containing smooth muscle cells. The framework tissue of the rete is more conspicuous at the cranial extremity of the testis, with a mio-connective matrix organization. PMID- 1897728 TI - Morphology of the endocrine pancreas in cyclosporine-treated glucose-intolerant Wistar rats. AB - The toxic effect of Cyclosporin A (CS-A) (1.25-50.0 mg/kg body weight) on the endocrine pancreas of Wistar rats was morphologically investigated. The treatment of animals with CS-A doses above 5 mg/kg for 2 weeks resulted in a disturbed glucose tolerance, a reduced B-cell volume density and degranulation, vacuolization and decreased mitotic activity of the B-cells. After withdrawal of the drug the impaired parameters were stepwise normalized, starting with regranulation of pancreatic B-cells, followed by a stimulation of mitotic activity, and increase of B-cell volume density. When continuing the CS-A treatment with doses lower than 5.0 mg/kg for longer periods we observed a decreased body weight gain and reduced pancreatic insulin content. PMID- 1897729 TI - [The structure of the mammary gland of cattle during the dry period with special reference to the involutional process. 1. Light microscopic studies]. AB - Light microscopical and histochemical investigations were performed on biopsies, which were obtained from the mammary glands of healthy pregnant cows during different stages of the nonlactating period. The results demonstrate characteristic morphological changes in the different phases of the nonlactating period. They can be interpreted as involution and regeneration processes, which occur in the alveoli and interalveolar tissue of the bovine mammary gland during the nonlactating period. PMID- 1897730 TI - [The structure of the clavicular air sac of the duck (Anas platyrhinchos)]. AB - The structural organization of the epithelium lining the clavicular air sac in Duck was studied by light and electron microscopic. This epithelium consists of two types of pavement like cells. The first flat types of cells are numerous with large mitochondria containing cytoplasm and elongated nuclei. The second short and dumpy cells are few in number and are after seen near the ostium. They could have long microvilli like pseudopod on their apical surface ready to engulf inhaled foreign particles. Desmosomal bridges too are found between contiguous cells. PMID- 1897731 TI - Undifferentiated spermatogonia and their role in the seasonally fluctuating spermatogenesis in the mink, Mustela vison. AB - Three classes of spermatogonia were discerned: undifferentiated A spermatogonia (Ais, Apr, Aal), differentiated A spermatogonia (A1, A2) and differentiated B spermatogonia (B1, B2). Cell counts performed throughout the seminiferous epithelial cycle in the breeding season revealed that the number of undifferentiated A spermatogonia was lowest in the presence of differentiated A1 and A2 spermatogonia during stages I-II to III-IV. In the non-breeding season a highly significant increase in the number of undifferentiated spermatogonia occurred in an animal with moderate germ cell loss exclusively at stages I-II to III-IV, when the A1 and A2 spermatogonia degenerated. In three other animals involved in severe cell loss, enhanced proliferation of undifferentiated spermatogonia was much greater than in the animal mentioned above. These result suggest the presence of a feedback mechanism between undifferentiated and differentiated spermatogonia, which may be considered to play an important role in regulating seasonal changes in spermatogonial proliferation. PMID- 1897732 TI - [Radiological and statistical determination of the morphological type of the canine skull: dolichocephaly, mesocephaly and brachycephaly]. AB - Cranio-encephalic morphology of three breeds of dogs (Greyhound, Pointer and Pekinese at the rate of 10 subjects, 5 males and 5 females, in each one) has been radiologically observed. Radiographic negatives in dorso-ventral and latero lateral positions were taken and analyzed before and after the visualisation of the encephalic cavity using barium sulfate. 18 cranio-encephalic measurements were chosen and interpreted statistically. The results showed that certain variables were more closely correlated with morphologic types of the cranium than others. We discuss the validity of the data applied for clinical diagnostic or osteo-archeology determinations. PMID- 1897734 TI - Arterial segmentation in the spleen of the sheep. AB - Forty six corrosion casts of sheep splenic artery and its intrasplenic tree were studied. Forty spleens (86.96%) showed two segments, 2 spleens (4.35%) revealed three segments and 4 spleens (8.69%) did not demonstrate arterial segmentation. PMID- 1897733 TI - [Spatial pattern and microvascularization of the ductuli efferentes testis of bulls (Bos taurus)]. AB - The arrangement, origin, course and opening of the ductuli efferents testis of the bull (Bos taurus) were visualized using scanning electron microscopy. The corresponding capillary structure was also described and documented with the help of corrosive microanatomical casts. The number of the ductuli efferents testis of the bull varies narrowly between 12 to 13. Ductuli removed from the surrounding tissue have a length of up to 78 cm. The duct system is composed of linear as well as tortuous parts, permitting division into three distinct segments. Blind ending ductules are very short. We therefore do not see these structures as being associated with spermiostasis. The capillary density as well as the capillary architecture show regional peculiarities. All segments of the ductuli efferents testis are composed of capillaries of the continuous type. The findings indicate that the increased capillary density in the voluminous initial section of the ductuli efferents testis represents the basis for resorptive as well as secretory activities in the bull. PMID- 1897735 TI - [Histochemical and immunohistochemical study of the lymphoid tissue of swine: lymphatic ganglia, spleen and thymus]. AB - Immunohistological (S-100, cIg) and enzyme histochemical (ANAE/ANBE, beta-glu, ATPase, AcP) investigations were carried out to identify lymphocyte and reticular cell subpopulations "in situ", in pig lymphoid tissue (lymph node, spleen, and thymus) of a 6 months old group, and a 6-9 days old one. By means of immunohistological techniques, in the 6 month old pigs we could detect S-100 protein (PAP), chiefly in T-areas lymphocytes, but we also found some S-100 positive lymphocytes in spleen follicles. Also S-100 protein were detected at Follicular Dendritic Cells (FDC) in lymph node and spleen; and Reticular Fibroblastic Cells (RFC) only in the first one. Finally, S-100 were noted in Hassall corpuscles (thymus), nervous fibres, and endothelial cells too. Using PAP (IgG, IgM) and IPI (IgA) techniques we could detect lymphocyte cytoplasmatic surface immunoglobulins (cIg) in lymphocytes, lymphoblastoid and plasmacytoid cells in nearly all tissue compartments. By means of histochemical techniques we could identify T-area lymphocytes ANAE/ANBE and beta-glu positives (cytoplasmatic spots) and B-area lymphocytes ATPase positive; macrophages, and polymorphonuclear eosinophiles PHNE being ANAE/ANBE and beta-glu positives (diffuse cytoplasmic stain); and Hassall corpuscles ANAE/ANBE and AcP positives. Concerning to reticular cells, we found FDC and RFC in lymphoid follicles, and Interdigitating Reticular Cells (IDC) in lymphoid diffuse tissue, with enzyme activity (all the enzymes studied) in nearly all the cases. In piglets, the immunohistological and histochemical pattern was nearly the same. PMID- 1897736 TI - [Histochemical study of the muscle fibers of some marine and fresh water teleost fish]. AB - Histochemical and morphological studies of skeletal muscle of some fresh and salt water fish is presented. Distribution of three muscle types, red, intermediate and white, is discussed. PMID- 1897738 TI - Linking the basic sciences in teaching: suggestions for histology instruction. PMID- 1897737 TI - [The microscopic and functional anatomy of the ileal papilla (papilla ilealis) and the cecocolic valve (valva caecocolia) and the pelvic flexure (flexura pelvina) of the horse (Equus caballus)]. AB - The histologic study on six horses of the ileo-caecal and caeco-colic junctions confirms their sphincteral structure. It appears that the activity of the muscular fibres, identified in the ileo-caecal and caeco-colic plica, modulates the curvature of the junctions and thus, blocks, as sphincters, the reflux of contents from the caecum into the ileum and from the colon into the caecum. But on the other hand, the pelvic flexure does not possess any microscopic organization to stop the reflux of contents from the dorsal colon into the ventral colon. PMID- 1897739 TI - Morphology of the ependymal cells of the bovine area postrema. AB - This communication describes the ultrastructure of the ependyma of the bovine area postrema. The polygonal cells possessed an abundant apical array of microvilli but were nonciliated with the exception of occasional cells at the periphery of the area, which had a central kinocilium. The low squamous cells contained moderate numbers of cytoplasmic organelles. The cells do not appear to be typically secretory, but may function in fluid exchange. PMID- 1897741 TI - Morphology of the synovium during its differentiation and development in the mouse knee joint. A histochemical, SEM and TEM study. AB - The prenatal and postnatal development of the mouse knee joint was investigated by transmission and scanning electron microscopy. In the prenatal stage, following the appearance of a narrow intercellular cleft between two skeletal elements on the 16th fetal day, clefting extended into the lateral synovial mesenchyme. In some regions, the extension of the cleft was very rapid, but in a certain region (future fat pad region), it was somewhat slower. Macrophage-like cells appeared in the synovial mesenchyme on the 16th fetal day, and then increased in number, and were distributed as if they were clustering around the presumptive clefting zone in the future fat pad region on the 17th-18th fetal day. This suggests that macrophage-like cells may participate in joint development, as they phagocytize and remove some kinds of solid extracellular matrix, and facilitate the cleft extension. In the early postnatal stage, scanning electron microscopic observations showed that there were two different types of cell in the synovial lining. One of them exhibited a surface morphology corresponding to that of macrophages: a spherical cell body and numerous pseudopodia. The other type of cell exhibited various cell shapes with many cytoplasmic processes extending along the synovial surface. PMID- 1897742 TI - Development of the amphibian oculomotor complex: evidences for migration of oculomotor motoneurons across the midline. AB - The development of the oculomotor nucleus in five species of salamanders and one anuran species was investigated with tracing techniques. The data presented support the hypothesis that oculomotor motoneurons innervating the superior rectus muscle migrate across the midline. In the salamander Pleurodeles waltl, only ipsilateral oculomotor motoneurons are labeled in early development. Later, these neurons extend dendrites toward the contralateral side into the ventral tegmental neuropil, after which there is displacement of their nuclei (neuronal somata) across the midline. Cell bodies can be observed directly at the midline. In adult Salamandra salamandra, motoneurons innervating the superior rectus muscle are seen occasionally at the midline and on the ipsilateral side, with dendrites toward the contralateral side. Motoneurons on the ipsilateral side do not display these features. In Pleurodeles, developmental brain processes are slowed down, and the sequence of development of the contralateral subnucleus, which can be clearly observed, supports the migration hypothesis. In Xenopus laevis and most other species of salamanders this process is accelerated. PMID- 1897743 TI - Dense granule-containing cells in the wall of the branchio-cardiac veins of a fresh water crayfish (Astacus leptodactylus). AB - The anatomical structure of oxygen-sensitive receptors in branchio-cardiac veins of a crayfish (Astacus leptodactylus) was studied with fluorescence and electron microscopy. Fluorescent cells were observed in the wall of a restricted part of the branchio-cardiac veins which was electrophysiologically shown to be a chemoreceptor region. Electron microscopy disclosed that they were dense granule containing cells, and form, together with supporting cells and nerve terminals, complex structures that show gross similarities with arterial chemoreceptor structures in vertebrates. PMID- 1897744 TI - Effects of visible light and room temperature on the ultrastructure of preimplantation rabbit embryos: a time course study. AB - In a time course study (4-20 h) rabbit early cleavage stages (day 1 p.c.) and compacted morulae (day 3 p.c.) were exposed to visible light or room temperature (23 degrees C), respectively. An 8 h light exposure of day 1 embryos caused alterations in nuclear morphology (lobulated nuclei, loss of nucleolar differentiation), an increased electron density of the cytoplasm, and cellular fragmentation leading to a considerable degeneration of blastomeres (central clustering of organelles, loss of cell surface differentiation) after a 20 h exposure. Room temperature exposure (compacted Day 3 morulae) led to decompaction and a cleavage delay after 8 h. After 10 h, arrested metaphases occurred in all examined morulae. Even after 20 h at 23 degrees C, day 3 embryos were at the decompacted morula stage, and showed metaphase-arrested blastomeres. The general morphology of the blastomeres was unaffected at this temperature, except for vacuolated ser- and cis-side vesicles of the Golgi complex at 8, 12 and 20 h, respectively. PMID- 1897740 TI - On the possible role of endogenous lectins in early animal development. AB - In this review I have tried to summarize the information available on the lectins of developing embryos. The emerging evidence indicates that during fertilization carbohydrate-binding proteins play a role in sperm adhesion and in the reorganization of the extracellular matrix of the fertilized egg. Results also indicate that in adult tissues lectins participate in cell recognition and adhesion, and that several galactose-binding lectins function as receptors for laminin and, in principle could also interact with polylactosamine groups of other extracellular matrix glycoproteins. Since in developing embryos lectins are located at the cell surface, and colocalize with extracellular matrix glycoproteins, they could play a role in transitory adhesive interactions and in the segregation of organ primordia. On the basis of experiments in cultured cell lines, it has been suggested that lectins are involved in lysosomal and nuclear glycoprotein transport. These carbohydrate-binding proteins could also regulate development by modulating these processes in the embryo. Since galactose-binding lectins are mitogenic, and are present in high concentration in the chick yolk sac, these proteins could be released into the embryonic circulation, bind to cells expressing appropriate receptors, and act as growth regulators, by modulating cell division of specific cell lineages. PMID- 1897745 TI - Asynchronous development of the rat colon. AB - Mucosal ridge and fold formation, apoptosis and the occurrence of secondary lumina within the epithelium are morphological features associated with the development of the colon. These processes, however, do not occur synchronously in the various segments of the colon. In the caecum and ascending colon of the rat, fold formation, apoptosis and secondary lumina result in the development of villi by day 22 after conception, and by postnatal day 3 in the transverse colon. These villi persist in the rat colon until approximately postnatal day 10. The presence of colonic villi may be correlated with the increased food intake and fluid absorption during this early postnatal period. Villus formation does not take place in the developing descending colon. PMID- 1897748 TI - Dynamic laser light scattering compared with video micrography for analysis of sperm velocity and sperm head rotation. AB - A new method which allows separation of the rotational and translational components of human sperm motility, based on the angular dependence of the dynamic laser light scattering (DLS) has been developed. The technique was used in a clinical study and was compared with an independent evaluation by video micrography. A good correlation was found between the two techniques when applied on different semen samples (r = 0.90; P less than 0.01 and r = 0.96; P less than 0.01 for rotation and translation, respectively) and when applied on the same semen sample at different temperatures. The rapid evaluation of these parameters using DLS technique opens the possibility to study large number of semen samples under physiological and pathological conditions at a lower cost. PMID- 1897746 TI - Observations on the development of ascending spinal pathways in the clawed toad, Xenopus laevis. AB - The development of ascending spinal pathways has been studied in the clawed toad, Xenopus laevis. From stage 35 (hatching) on, HRP was applied at the spinomedullary border or to the area of the developing dorsal column nucleus, to analyze the development of ascending spinal pathways to the brain stem, and the onset and development of spinal projections to the dorsal column nucleus, respectively. Several populations of spinal neurons with ascending projections at least as far as the spinomedullary border were successively labeled. In early stages ascending spinal projections arise from Rohon-Beard cells and ascending interneuron populations located at the margin of the gray and white matter, i.e., marginal neurons. The ascending interneuron populations could be characterized as dorsolateral commissural and commissural interneurons projecting contralaterally, and as ipsilaterally projecting ascending interneurons and distinguished by Roberts and co-workers. Such a subdivision could be made until about stage 57. Then these ascending and commissural interneuron populations become intermingled with other populations of ascending tract neurons. Rohon-Beard cells could be labeled, more or less shrunken, until stage 55. Around stage 48 (at the time of the appearance of the limb buds) spinal ganglion cells could be labeled from the spinomedullary border and the developing dorsal column nucleus. At stage 48 such ascending primary spinal afferents were found to arise only from non-limb-bud innervating dorsal root ganglia. Gradually also the limb-bud-innervating ganglia give rise to ascending collaterals, so that by stage 53 all spinal ganglia send ascending collaterals to the brain stem. The number of cells of origin of secondary spinal afferents to the brain stem increases during development, and their distribution becomes more extensive. Particularly impressive is a large population of neurons in the dorsal horn projecting ipsilaterally to the dorsal column nucleus. Part of the latter population represents non-primary spinal afferents to the dorsal column nucleus. PMID- 1897747 TI - Comparative morphometry of Bergmann glial (Golgi epithelial) cells. A Golgi study. AB - Bergmann glial (Golgi epithelial) cells were Golgi-impregnated in the cerebella of species with great differences in the thickness of the molecular layer, in small African native mouse, rat, rhesus monkey, and man. The thickness of the molecular layer determines the length of the radial Bergmann cell processes. Whereas the overall morphology of the cells was found to be strikingly similar in all species studied, there were great quantitative differences in length and diameter of the stem processes. Species with thick molecular layers (man, monkey) have thicker stem processes than species with short distances between Bergmann glial cell soma and pial surface (rat, mouse). This could mean that larger animals with longer gestation periods allow for prolonged growth of cell volumes. On the other hand, an increase in the diameter of long processes should reduce the cytoplasmic resistance against ionic currents; this would be important when Bergmann glial cells--like retinal Muller cells--would act as "cables" for spatial buffering of potassium ions released by electrically active neurons. By contrast, the fractal dimension--i.e., a quantitative measure of the complexity of the cell's border--of the cell processes was lower in species with long processes. In an age series of rat cells, the fractal dimension is shown to increase slightly up to a very old age. PMID- 1897749 TI - Techniques for improving the accuracy and efficiency of the sperm penetration assay. AB - Six different techniques were evaluated for improving the accuracy and efficiency of the sperm penetration assay (SPA). Flushing and puncture of the oviduct were found to result in similar recovery of eggs from the oviduct, percentage of penetrated eggs, and penetrations per egg. However, the time required to flush the oviduct tended to be longer than for the puncture technique. Exposure of eggs to a 5% formalin solution prior to mounting resulted in fewer ruptured eggs, greater recovery of eggs, and a reduced time to mount and read the eggs compared to eggs not exposed to formalin. The percentage of penetrated eggs and penetrations per egg were similar for formalin exposed and nonexposed eggs. Significantly fewer penetrated eggs and penetrations per egg were noted when eggs were read as fresh mounts compared to eggs that were fixed and stained prior to evaluation. A significantly longer time was also required to read the freshly mounted eggs compared with the stained eggs. The results of these studies indicate that to maximize the accuracy and efficiency of the SPA, cumulus masses should be removed from the oviducts by puncture, eggs should be placed in a 5% formalin solution before mounting on slides, and eggs should be fixed and stained prior to evaluating for penetrations. PMID- 1897750 TI - Swim-down separation of progressively motile sperm from poor quality human semen by the modified funnel procedure. AB - The simultaneous swimming up and down from identical semen specimens suggested that the separation efficiency of progressively motile sperm by the swim-down method was superior to that of the swim-up method. The swimming down was performed in a small plastic funnel, the bottom of which was plugged with a 2.5 ml disposable syringe. In this funnel, 2.0 ml of 70% Percoll was poured and then the sperm resuspension was overlaid. After 1 h, progressively motile sperm penetrating into the lower part of Percoll layer (1.6 ml) was collected in the syringe. The technical strategies to yield higher density of progressively motile sperm were found to be centrifugal concentration of the sperm from whole ejaculate prior to the swimming down, and subsequent re-centrifugation of the separated sperm after the swimming down. Oligo-asthenozoospermic semen (22 +/- 4.4 x 10(6) ml1, 5.5 +/- 4.4% motility, n = 8) was processed by the present method, yielding sperm qualities of 32 +/- 19 x 10(6) ml1, 74 +/- 14% in the final preparations. Overall improvement in fertility index (sperm density ml1 x motility % x 10(8)) reached 27-folds on average. PMID- 1897751 TI - Comparison between a conventional index of progressive sperm motility and movement variables analysed by CellSoft. AB - Two different techniques of human sperm motion analysis were compared. In 25 ejaculates, diluted to an appropriate concentration, the sperm motion index called "specific progressive motility" (SPM) was assessed by a modified conventional method. The same sperm preparations were also analysed by the CellSoft system for computer assisted sperm analysis (CASA). The SPM-value was found to correspond mainly to the variables motility and curvilinear velocity presented by CASA (multiple r = 0.92, P less than 0.001). Linearity of sperm progression, lateral head displacement, and beat cross frequency did not significantly contribute to the relationship between SPM and CASA. For comparative studies between SPM and CASA the logarithmic values of SPM are recommended. PMID- 1897752 TI - Concentrating human sperm before cryopreservation. AB - To improve the quality of cryo-preserved sperm, ejaculated semen was concentrated prior to freezing by means of continuous-step density gradient centrifugation. Freezing was simplified by employing liquid nitrogen vapor with KS-II cryo medium. The original semen (n = 32, 41 +/- 13 x 10(6)/ml, 17 +/- 11% motility) was improved by the processing to be 68 +/- 29 x 10(6)/ml, 55 +/- 19% motility. Even after the specimens were thawed, sperm concentrations were similar to those of the original semen and 39 +/- 18% motility remained with a mean survival rate of 74 +/- 7.7%. The improved sperm motility and higher survival rate resulted in better post-thaw sperm quality than those of the original semen. PMID- 1897753 TI - The importance of employing stringent methods to recruit fertile male controls. AB - Two methods of recruiting fertile male controls were evaluated and compared. The first group was recruited from the partners of women attending an antenatal clinic without obtaining details of their reproductive history. The second group was recruited after obtaining a detailed reproductive history from the couple and employing stringent entry criteria. Entry criteria for the second group included a length of exposure to the risk of pregnancy of not more than 12 months and no previous episode of involuntary infertility for either partner. There were significant differences between the distributions of semen parameters obtained from the two groups, indicating that the selection criteria for "fertile" men significantly influence results obtained and therefore that it is important to employ stringent criteria for the recruitment of fertile male controls. The group which was recruited by stringent criteria (mean length of exposure to the risk of pregnancy of 3 months) was characterised by a significantly higher median concentration of spermatozoa which exhibited slow linear or nonlinear motility. This confirms the findings of a previous study which suggested that slow linear or nonlinear motility are superior forms of spermatozoal motion. PMID- 1897754 TI - Cellular sensitization against sperm and seminal antigens in women. AB - In 13 healthy women and 6 virgins the cellular sensitization against sperm and seminal plasma antigens was demonstrated by an indirect lymphokin assay, the leucocyte migration inhibition test (LMI-test) using the following preparations: "washed" spermatozoa, seminal plasma and spermatozoa of the supernatant prepared with the "swim-up" technique. In both groups of women a cellular sensitization against sperm and seminal plasma antigens could be observed. Further, a dose dependent correlation was found in that way, that increasing concentrations of spermatozoa lead to an increased inhibition of macrophage migration. In virgins cellular sensitization against seminal plasma proteins did not differ from non virgins, only the percentage of significant reactions in the LMI-Test was reduced. As low sperm concentrations (1 million ml-1), which represent best the physiological situation in the uterus, induced an enhanced migrations of macrophages the enhancement of macrophage migration is considered as physiological cellular sensitization of females against sperm-associated antigens. PMID- 1897755 TI - Effectiveness mechanism of chlomipramine by neurophysiological tests in subjects with true premature ejaculation. AB - The effectiveness mechanism of the chlomipramine treatment was evaluated by sacral evoked response (SER) and dorsal nerve somatosensory cortical evoked potential (DN-SEP) testings in 15 patients with true premature ejaculation (TPE). We couldn't demonstrate any significant difference between the values of either latency times or amplitudes of the evoked responses determined just before and at the end of the treatment with chlomipramine in these patients. However, the sensory thresholds were 24.4 +/- 4.3 V in the pretreatment term and 30.2 +/- 7.3 V at the end of the treatment. This difference is statistically significant (P = 0.0031). Our results suggest that chlomipramine increases the sensory threshold for the stimuli in the genital area. PMID- 1897756 TI - Effect of sleep deprivation on the physiological status of rat testis. AB - The effect of alteration of central turnover of monoamines on the intratesticular mechanisms in the testis of rats was studied after REM sleep-deprivation. The reduction in the weights of ventral prostate, seminal vesicles and decreased activity of beta-glucuronidase in kidney reflected decreased availability of testosterone to the target organs. Decreased activities of lysosomal enzymes, acid phosphatase and beta-glucuronidase were associated with a decreased steroidogenic activity in the testis. The active mediation of lysosomal enzymes in the testicular function under altered condition was indicated. PMID- 1897757 TI - Alterations in protein profile of rat spermatozoa during maturation. AB - Alterations in the polypeptide pattern of rat spermatozoa during epididymal transit were studied by SDS-PAGE and compared with that of epididymal cytosol and luminal fluid. The total number of cytosol and luminal fluid polypeptides increase from caput to cauda epididymidis but sperm associated polypeptides decrease during epididymal transit. Changes in polypeptide pattern of spermatozoa are due to their acquisition, loss or modification. Spermatozoa acquire seven polypeptides, of which six are acquired in corpus (MW 16.5, 38, 41, 72, 75 and 100 Kdal) and one (MW 28.5 Kdal) in cauda epididymidis. Spermatozoa lose one polypeptide of MW 72.5 Kdal in caput and two polypeptides of MW 70 and 115 Kdal in cauda epididymidis. Four polypeptides of MW 18.5, 19.5, 64 and 67.5 Kdal disappear from cauda spermatozoa without appearing in the luminal fluid. Polypeptide of MW 62.5 Kdal is observed only in spermatozoa and luminal fluid from cauda epididymidis. PMID- 1897758 TI - Parathyroid hormone: another pregnancy protein present in human seminal plasma and amniotic fluid. AB - Parathyroid hormone (PTH) has been found in human seminal plasma at concentrations of 302 +/- 65 (222-482) pmol l-1 (n = 16), which is about 5 times the concentration in human blood serum. Concentrations in human amniotic fluid at 16-22 weeks of gestation were 43 +/- 9 (28-65) pmol l-1 (n = 24), which is about 80% of the concentration in blood serum. The Amersham assay uses an antiserum raised against the synthetic middle piece of the PTH molecule from the parathyroid glands. It estimates amino acids 44-68 of the 84 amino acid intact molecule, together with fragments containing this part of the chain. It is considered that a placental type of parathyroid hormone was being measured, some of which escapes into the amniotic fluid. The placenta contains a complete PTH dihydroxyvitamin D3 system that causes the absorption of more calcium from the gut for foetal needs during pregnancy. It is postulated that the seminal vesicles also contain a PTH-dihydroxyvitamin D3 system that has a paracrine action in passing large amounts of calcium into the ejaculate. PMID- 1897759 TI - Radio-immuno binding test for anti-sperm antibody detection: analysis and critical revision of various methodological steps. AB - The authors report the results of a methodological study to optimize a radioimmunoassay to detect anti-sperm antibodies. They describe here the definitive methodology with all the data relating to the laboratory trials conducted at each step of the technique. Results seem to demonstrate that this radioimmunological method is sufficiently simple, specific, sensitive and reliable for use in a highly specialized laboratory of reproductive immunology. Furthermore, this type of analytical approach, whilst indicating once more the difficulty of the technical study of anti-sperm autoimmunity, confirms (with concrete data) the necessity of being extremely "prudent" in evaluating the results of this kind of anti-sperm antibody test. PMID- 1897761 TI - Evaluation of human sperm motility by means of transmembrane migration method and computer assisted semen analysis: a comparison study. AB - Comparing motility parameters with a trans-membrane migration method and a Hamilton-Thorn HTM-2000 computer assisted semen analyzer, we found that trans membrane migration ratio (TMMR) correlated best with critical motility which indicated the fraction of fastest and straightest sperm in a semen sample. We also found that TMMR correlated better with progressive velocity than with track speed. It is concluded that nonprogressive sperm were not included in the estimation of TMMR and the trans-membrane migration method is most suitable for studying drug effect on straight and rapid sperm motility. PMID- 1897760 TI - Correlation between gamma seminoprotein in seminal plasma and ejaculate parameters. AB - Gamma seminoprotein (G-SM) levels in seminal plasma were determinated in 62 ejaculates using an enzymimmunoassay. There was no statistical significant difference in G-SM between men with normozoospermia (n = 14), asthenozoospermia (n = 17), OAT-syndrome (n = 18) and azoospermia (n = 13). Also there was no correlation of G-SM levels in those samples with normal (n = 14) or pathological (n = 35) motility and normal (n = 17) or pathological (n = 32) swelling test. Ejaculates with high viscosity (n = 12) showed similar G-SM levels than those with normal (n = 50) viscosity. According to these results seminal G-SM levels does not appear to provide an useful marker for evaluation of male fertility. PMID- 1897762 TI - Ultrasonography revealing the accumulation of rete testis fluid in bull testicles. AB - Ultrasonography was used for diagnosing accumulation of rete testis fluid in live bulls. When 447 bulls of Ayrshire breed selected for artificial insemination were studied by ultrasonography, eleven were detected in which the ultrasonograms visualized accumulation of rete testis fluid in the testicles. In 7 bulls the accumulation (spermiostasis) was bilateral and in 4 unilateral. In only four out of 18 testicles, macroscopically epididymal cysts were seen after slaughter. At the age of 16 months four bulls with bilateral spermiostasis were azoospermic. When studied by ultrasonography, the rete testis of normal testicles was echogenic and narrow but in affected testicles anechogenic and wide. Nine of the affected bulls were sons of three fathers. We suggest that spermiostasis is hereditary in Ayrshire bulls and, as in the goat, is progressive by nature. PMID- 1897763 TI - Treatment of acute systemic toxicity after the rapid intravenous injection of ropivacaine and bupivacaine in the conscious dog. AB - Two groups of six beagle dogs received rapid intravenous (IV) injections of ropivacaine or bupivacaine on two occasions in a blinded random fashion. Initially, a dose sufficient to cause convulsions (CD) was given followed by twice the CD (2 x CD), which was administered 48 h later. The CD of bupivacaine (4.3 mg/kg) and ropivacaine (4.9 mg/kg) caused significant (P less than 0.05) increases in heart rate and mean arterial blood pressure. There was no difference between drug groups. Seizures were abolished by 10 mg/kg of intravenous thiamylal. Endotracheal intubation and controlled respiration with O2-enriched air with no other treatment resulted in rapid and complete recovery in all dogs. All dogs receiving 2 x CD of bupivacaine (8.6 mg/kg) or ropivacaine (9.8 mg/kg) were initially treated with thiamylal and mechanical ventilation. Two dogs in the bupivacaine group developed hypotension, respiratory arrest, ventricular tachycardia, and ventricular fibrillation, which were resistant to closed chest cardiac massage, treatment with epinephrine, bretylium, and atropine, and direct current cardioversion. The four remaining dogs in the infusion group were successfully resuscitated. All of the animals in the ropivacaine-treated group survived the administration of the 2 x CD dose. Mild hypotension developed in one dog and was treated with intravenous epinephrine (0.75 mg). This resulted in nodal tachycardia, which was abolished after treatment with bretylium. Another dog had two 1-s bursts of premature ventricular contractions requiring no treatment. The rapid treatment of convulsions and cardiovascular toxicity resulted in a decreased number of deaths in both groups when compared with dogs from a previously published study in which no therapy was instituted. Thus, early aggressive treatment of central nervous system and cardiovascular system toxicity is capable of reducing the incidence of mortality associated with the rapid intravenous administration of excessive doses of local anesthetics. PMID- 1897764 TI - Heart rate responses to body tilt during spinal anesthesia. AB - To evaluate whether low-pressure baroreceptors located in the right atrium could affect the heart rate (HR) during spinal anesthesia, the authors determined the effects of right atrial pressure changes associated with body tilt on HR in 40 unpremedicated patients. Ten-degree head-up body tilt produced significant increases in HR of 6 +/- 1 and 6 +/- 1 beats/min (mean +/- SE, P less than 0.01) and significant decreases in systolic arterial pressure of 2.8 +/- 0.9 and 6.6 +/ 1.7 mm Hg (P less than 0.01) during low (T-10 +/- 0.2, n = 20) and high (T-4 +/- 0.2, n = 20) analgesic levels of tetracaine spinal anesthesia, respectively. Ten degree head-down body tilt caused significant decreases in HR without significant changes in systolic arterial pressure during spinal anesthesia. The reflex HR responses to body tilt were similar between low and high levels of spinal anesthesia and were preserved after administration of sedatives. The magnitudes of changes in right atrial pressure associated with body tilt were similar during spinal anesthesia and after sedation. These findings suggest that HR responses to head-up body tilt are mediated mainly by arterial baroreceptors even in the face of decreased venous return during low or high levels of spinal anesthesia and that light sedation does not impair this reflex HR response. PMID- 1897765 TI - Level of spinal anesthesia can be predicted by the cerebrospinal fluid pressure difference between full-flexed and non-full-flexed lateral position. AB - We studied whether cerebrospinal fluid pressure difference between full-flexed and non-full-flexed lateral position (dP) influences the spread of intrathecally (i.e., spinal) administered anesthetic solution (SSA). Forty-two women, 18-60 yr old, who underwent gynecologic surgery under spinal anesthesia were enrolled in the study. They were divided into two groups (group 1: less than 40 yr old, group 2: greater than or equal to 40 yr old). Before spinal anesthetic injection, we measured the pressure difference produced by postural change from the right lateral decubitus position (non-full-flexed) for needle insertion at the L2-3 interspace to a full-flexed lateral decubitus position with a spinal needle in place. After they returned to the non-full-flexed lateral position, 14 mg of plain tetracaine in 10% dextrose solution (2.8 mL) was injected intrathecally in each patient. Pressure differences had a significant correlation with the cephalad levels of spinal anesthesia in each group; the larger pressure difference was associated with a larger SSA. The relationship was stronger in the younger group (correlation coefficients, 0.82 and 0.63; P-values less than 0.01 in groups 1 and 2, respectively). Three patients in group 1 developed T-2 anesthesia, whereas no one in group 2 did (P less than 0.01), and their pressure difference values ranged from 12 to 16 cm H2O, substantially larger than those of the other patients in group 1. Five patients in group 2 developed T-3 anesthesia, whereas no patient in group 1 (P less than 0.01) did, and their pressure differences were not essentially larger than those of the rest in the same group. The authors conclude that pressure differences correlated with the SSA, although the mechanism remains to be clarified. It seems possible to predict which patient in the younger patient group may develop unintentional high spinal anesthesia (T 3 or higher) by measuring pressure differences. PMID- 1897766 TI - Comparison of 40 milliliters of 0.25% intrapleural bupivacaine with epinephrine with 20 milliliters of 0.5% intrapleural bupivacaine with epinephrine after cholecystectomy. AB - To determine the influence of the volume of local anesthetic injected for intrapleural analgesia, 40 patients undergoing cholecystectomy were randomly allocated to two groups of 20 patients each. One group received 40 mL of 0.25% bupivacaine with epinephrine injected intrapleurally postoperatively. The other group received 20 mL of 0.5% bupivacaine with epinephrine. The onset time of analgesia was nearly the same in both groups and within 25 min all patients were nearly pain free. Our data demonstrate that 100 mg of bupivacaine with epinephrine elicits effective analgesia after cholecystectomy. There are only minor differences between 20 and 40 mL with regard to pain relief. The authors conclude that the volume of local anesthetic within the range of 20-40 mL in an adult has little influence on the extent or duration of intrapleural analgesia. PMID- 1897767 TI - Respiratory function and ribcage contribution to ventilation in body positions commonly used during anesthesia. AB - Lung function tests are normally performed in the upright position, whereas anesthesia is usually administered with the patient in the supine position, and occasionally in other postures. We therefore compared forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), functional residual capacity (FRC), and ribcage contribution to ventilation by respiratory inductive plethysmography in 13 conscious healthy male volunteers, sitting and in four horizontal positions used during anesthesia. Forced vital capacity and FEV1 were similar in all positions, except for a significant mean increase in FVC of 300 mL (SD 213) when sitting compared with when supine (P less than 0.001). The mean decrease in FRC was 806 mL (SD 293) between the sitting and supine positions (P less than 0.001). A significant increase in FRC occurred (252 mL, SD 329, P less than 0.01) when supine subjects raised their arms above their heads as required for computed tomography. Functional residual capacity in the prone and lateral positions was significantly larger than in the supine position (mean change 350 mL, P less than 0.001), but was still some 450 mL less than in the sitting position. Mean ribcage contribution was similar in all horizontal positions (32% 36%), whereas supine values were significantly different from those of the sitting position (mean 70%, SD 11, P less than 0.001). In conclusion, the various horizontal postures studied have no effect on FVC, FEV1, or ribcage contribution to ventilation. However, FRC in the prone, lateral, and arms-up positions is on average 250 mL larger than in the supine position, an observation that may affect gas exchange during anesthesia in these positions. PMID- 1897768 TI - Enhanced potency of receptor-selective opioids after acute burn injury. AB - Dose-response curves of three receptor-selective opioids were established in a group of nonburned and a group of burned rats. Morphine (mu-agonist), biphalin (mu- and delta-agonist), and U50488H (kappa-agonist) were administered to each group, and analgesia was measured by tail flick latency testing. Each opioid had a significant increase in potency (i.e., a decrease in ED50 values) in the burned (15% body surface area) compared with the nonburned groups. Moderate doses of each drug (i.e., ED50 doses estimated from nonburned group data) in each case augmented stress-induced analgesia in the burned group. Analgesic doses failed to prevent a significant increase in plasma beta-endorphin and corticosterone after larger surface area (25%) burns. Regardless of receptor specificity, opioid analgesic potency is increased acutely after burn injuries. PMID- 1897769 TI - Adverse interaction between bupivacaine and halothane on ventricular contractile force and intraventricular conduction in the dog. AB - Regional anesthesia with bupivacaine in pediatric patients is often accompanied by light levels of halothane general anesthesia. To determine the potential cardiotoxicity of these two drugs when used together, we defined the interaction between moderate plasma bupivacaine concentrations (1270-1760 ng/mL) and halothane (end-tidal concentrations, 0.5%-1.0%) on ventricular contractility and conduction in 22 closed-chest dogs anesthetized with chloralose. Bupivacaine alone (1-mg/kg intravenous bolus plus a 0.1-mg.kg-1.min-1 constant rate infusion) resulted in significant increases in ventricular conduction time (VCT) and effective refractory period (VERP) and nonsignificant decreases in dP/dtmax and blood pressure. The addition of halothane resulted in hypotension and in progressively increasing plasma bupivacaine levels secondary to reduced hepatic clearance, which led to further dose-related significant increases in VCT and VERP and to significant decreases in dP/dtmax and blood pressure. In other dogs given halothane but in which bupivacaine levels were held constant (1400 ng/mL), VCT remained constant and VERP lengthened slightly, whereas dP/dtmax decreased. We conclude that the combination of bupivacaine and halothane can cause adverse effects on ventricular contractility and intraventricular conduction. PMID- 1897770 TI - Clonidine decreases plasma catecholamines and improves outcome from incomplete ischemia in the rat. AB - Clonidine decreases central sympathetic activity and anesthetic requirement. We tested whether clonidine improves outcome from incomplete ischemia of the brain in rats. Control rats were anesthetized with 25 micrograms.kg-1.h-1 of intravenous fentanyl and inhalation of 70% nitrous oxide (N2O). Clonidine-treated rats received fentanyl/N2O and 10 micrograms/kg of intravenous clonidine 10 min before ischemia, which was produced by right carotid ligation combined with hemorrhagic hypotension to 35 mm Hg for 30 min. Clonidine increased plasma glucose before ischemia and decreased blood catecholamine concentrations during ischemia compared with the control group. Neurologic outcome was evaluated daily for 3 days after ischemia and histopathology was performed at the end of this period. Clonidine significantly improved neurologic outcome on each of the 3 days after ischemia. Histopathology was severe in the control group but not enough rats survived in this group for statistical analysis. The authors conclude that clonidine decreases sympathetic activity during ischemia and that this is associated with an improvement in outcome from incomplete ischemia. PMID- 1897771 TI - Administration of inhaled anesthesia with high-frequency oscillation: an in vitro study. AB - To assess administration of inhaled anesthesia during high-frequency oscillation, we evaluated the performance of a high-frequency oscillator that permitted incorporation of a precision vaporizer. The ventilator design used a single gas source for both vaporizer circuit and ventilatory support. The performance was evaluated in conjunction with a test lung device. The vaporizer performance was accurate when high-frequency, low-volume gas flow was used to provide source gas for the vaporizer. The ventilator provided accurate halothane delivery to the test lung device. Based on the results of this study, inhaled anesthesia can be accurately administered in conjunction with high-frequency oscillation. A single gas source that transverses the vaporizer before breathing circuit entrainment is critical for accurate results. PMID- 1897772 TI - Airway management for trauma patients with potential cervical spine injuries. PMID- 1897773 TI - Perioperative management for laryngotracheal reconstruction. PMID- 1897774 TI - Mainstem bronchial obstruction secondary to nasotracheal intubation: a case report and review of the literature. PMID- 1897775 TI - Rumination risk of aspiration of gastric contents in the Prader-Willi syndrome. PMID- 1897776 TI - Pheochromocytoma in a patient with Eisenmenger's complex. PMID- 1897777 TI - Prevention of tachycardia and hypertension associated with tracheal intubation. PMID- 1897778 TI - Cerebral circulation and oxygen uptake parallels. PMID- 1897780 TI - Hyperacusis after spinal anesthesia. PMID- 1897779 TI - Bupivacaine toxicity after stellate ganglion block. PMID- 1897781 TI - A method to assess correct endotracheal tube placement. PMID- 1897782 TI - Causalgia induced by telephone-mediated lightning electrical injury and treated by interpleural block. PMID- 1897783 TI - Near mishap in drug administration due to similarity between drug packaging. PMID- 1897784 TI - A simple method to retrieve irretrievable epidural catheters. PMID- 1897785 TI - [Monitoring somatosensory evoked potentials during surgery of cerebral vessels]. AB - In 43 patients serial SSER recordings were made during operations for the clipping of arterial aneurysms of cerebral vessels performed under controlled arterial hypotension. SSER recordings during the preliminary phase of the operation showed an average decrease in the response amplitude of 20% during trepanation and a reduction (by 23% of the initial value) during the phase of arterial hypotension. The response recovered to 84% of its initial level by the moment of the beginning of the operation. There was no statistically significant relationship between serial SSER parameter values during arterial pressure reduction and the duration or degree of hypotension. The results testify to the higher information content of such SSER parameters as the amplitude of the first positive complex, as compared with latency criteria and in particular the CCT. It has also been found that a significant increase in the information value of the SSER for the evaluation of ischemia effect on the brain function may be obtained by synchronous stimulation of both arms and registration of cortical responses from both hemispheres. PMID- 1897786 TI - [Carbohydrate metabolism of the brain in hypoxia]. AB - Using the data of arteriovenous differences, it has been for the first time demonstrated that patients with severe craniocerebral trauma (SCST) are characterized by glucose release by brain tissue combined with (p less than 0.05) pyruvate consumption. The above phenomenon is more often (p less than 0.05) associated with a more favourable course of SCST. A hypothesis is suggested of carbohydrate synthesis in hypoxia-affected brain tissues as a natural compensatory process. Conditions for gluconeogenesis are formed round macro- and microareas of brain damage with anaerobic metabolism bordering on tissues with aerobic metabolism. The process is responsible for energy and metabolic integration of disintegrated structures. Biological expediency of gluconeogenesis is glucose supply of anaerobic metabolism area with utilization of toxic metabolites, indirect energy maintenance of the affected area. Literature data supporting the hypothesis are presented. PMID- 1897787 TI - [Carbohydrate metabolism in the brain in comatose states. Mechanisms of gluconeogenesis]. AB - Glucose release and lactate uptake by the brain during coma is discussed. A hypothesis of autonomous gluconeogenesis in the brain is suggested. To substantiate the hypothesis use is made of the literature data on the presence in the brain of stimuli, and its provision with substrates and gluconeogenetic enzyme apparatus. Special attention is paid to the problem of gluconeogenesis energy supply during hypoxia, using proton or sodium potentials. PMID- 1897788 TI - [The use of the Siggaard-Andersen model of the oxyhemoglobin dissociation curve in patients in the immediate period following open heart surgery]. AB - A total of 300 patients have been examined on the first-third day after surgical correction of acquired heart valve defects, aortocoronary bypass surgery, and left ventricular postinfarction aneurysm resection performed using cardiopulmonary bypass technique. The parameters of the cardio-respiratory system and the value of parameter a in Siggaard-Andersen oxyhemoglobin dissociation curve (ODC) model have been studied. It has been shown that in some patients (about 5%) arterial blood hemoglobin saturation with O2 was lower than the corresponding blood pO2. In respiratory failure, parameter a decreases and the arterial part of ODC is shifted to the left, while in circulatory failure and hypoxia, parameter a of the venous blood increases and the curve is shifted to the right. The corresponding disorders corrected, the shifts are normalized. In severe postoperative complications and critical conditions additional (beside Bohr's effect and 2,3-diphosphoglycerate /2,3-DPG/ impact) ODC shifts, if any, are less marked. A statistically significant and considerable shift in parameter a of arterial ODC segment, as compared to venous one, has been observed. This ODC deviation from the model cannot be accounted for by pH, pCO2 or 2,3-DP impact. It can't be so far excluded that the effect observed might be partially due to regular errors of the measuring devices. However, it might turn out to be a new phenomenon of compensatory ODC shape changes in patients with acute cardiorespiratory disorders. PMID- 1897789 TI - [The use of selective cytopheresis following cardioplegia during open heart surgery]. AB - The analysis of 20 operations on the open heart performed with selective cytopheresis (apparatus PK-0.5) or without it has demonstrated that in pharmacological and ice-chip cardioplegia the technique to a great extent prevents the loss of the patient's own blood removed with cardioplegic solution and makes it possible to reduce donor blood consumption by 27%. The course of the postoperative period improves considerably: blood loss is reduced, the recovery of blood cellular composition becomes more intensive. Cardioplegia performed in combination with selective cytopheresis does not exclude certain protein loss (up to 15 g/l during one session), which confirms the necessity of adequate homeostasis correction with protein blood preparations. PMID- 1897790 TI - [The safety of anesthesia for the patient in the USA]. PMID- 1897791 TI - [The concentration of calcium and its fractions during heart surgery using extracorporeal circulation]. AB - Changes in the concentration of calcium and its fractions have been studied in 115 patients subject to standard bypass techniques. It has been found that calcium homeostasis disturbances do really develop and are caused by the use of solutions that are not balanced with blood in their calcium content. The main source of calcium in hemodiluents was gelatinol. A decrease in gelatinol volume to 450-600 ml prevented the onset of marked hypercalcemia. As ionized calcium (Ca2+) concentration is determined not only by the total Ca level, but also by the shifts in the degree of pH- and pCO2-dependent ionization and binding and in ligand and protein content, Ca2+ determination is considered an optimal method of calcium homeostasis control during cardiopulmonary bypass. PMID- 1897792 TI - [Changes in the liver circulation and kidney function during pulsatile and non pulsatile perfusion]. AB - Pulsatile flow perfusion (PFP) requires smaller volume of additional infusion. Extravascular hyperhydration is more marked after nonpulsatile flow perfusion (NPFP). In NPFP there is an increase in free water clearance, lower urinary osmolality and diuresis rate. PFP prevents urinary hypoosmolality and retains baseline values of free water clearance. No significant differences in Na+ urinary excretion have been revealed. Bilirubinemia level following NPFP was significantly higher than the baseline level, while following PFP the level of total and bound bilirubin remained unchanged. No differences in the total hepatic flow have been observed during pulsatile and nonpulsatile flow perfusion. PMID- 1897793 TI - [Assessment of the functional status of the left and right ventricles in the intact and damaged heart during volume overload]. AB - Changes in hemodynamics, reserve capacities of intact and damaged myocardium have been studied, with the left and right ventricular functions during mounting volume load assessed separately. It has been shown that exclusion of the part of left ventricular myocardium from contraction deteriorated considerably the pump and contractile function not only of the left but also of the right intact heart ventricle. Heart failure in volume overload manifests itself primarily in the right ventricle and depends on the functional heart reverse on the whole: in animals with partial injury of left ventricular myocardium heart failure developed in much lower volume loads than in intact animals. In circulation volume overload, left or right ventricular stroke work index to preload or filling pressure in the corresponding heart chamber ratio was most adequate and prognostically valuable for the detection of latent heart failure. PMID- 1897795 TI - [Sudden cardiac death and late ventricular potentials]. PMID- 1897794 TI - [Central hemodynamics and phase structure of the left ventricular systole during peritoneal dialysis in poisoning with organophosphate insecticides]. AB - Central hemodynamics and myocardial contractility have been studied during intermittent peritoneal dialysis (PD) in 46 patients with severe poisoning with organophosphorus insecticides (OPI). The volume of liquid, administered into the abdominal cavity for 30-40 min, was 1.5-2 1. During PD no considerable disturbances in the parameters under study have been observed irrespective of the baseline blood pressure level. That is why PD is recommended in patients with most severe forms of OPI poisonings accompanied by marked disturbances in hemo- and cardiodynamics. PMID- 1897796 TI - [The concentrations of somatotropic hormone and insulin in the blood of heart surgery patients with a complicated course of the postoperative period]. AB - It has been shown that the course of the early postoperative period in cardiosurgical patients and its outcome is to a great extent related to adequate balance of adaptation hormones, whose levels and changes are determined by the functional state of compensatory-adaptive systems. Patients with favourable outcome of the complicated postoperative period along with synchronous activation of sympathoadrenal system (SAS), hypophyseoadrenal system (HAS) and an elevated somatotropic hormone (STH) level demonstrated adequately high blood insulin content, with the equilibrium in adrenalin/insulin and cortisol/insulin ratios retained, and moderate STH predominance over insulin. In 1/4 of patients with complicated postoperative period and unfavourable outcome an attenuated SAS response was accompanied by excessively high STH, ACTH, cortisol blood content and a lower insulin level, which determined relative insulin insufficiency. PMID- 1897797 TI - [Optimization of the functional activity of the adrenal cortex in patients with sepsis]. AB - The effect of hemosorption on adrenal steroidogenic reactions has been studied in 75 patients with sepsis. Different variants of steroidogenesis optimization have been used. Hemosorption led to an increase in the level of steroid hormones, with this background retained throughout the whole treatment period. The most effective of all the variants of stress adrenal steroidogenic reactions optimization was the application of B, B1, B6, B12 vitamin complex and taktivin. The least effective was the application of B vitamin complex, taktivin and ultraviolet blood irradiation. The technique elaborated makes it possible to avoid an increase in steroid blood level during treatment, which must have a favorable effect on the recovery of immune homeostasis in the patients. PMID- 1897798 TI - [The antioxidant oxypyridine-6 as an agent for preventing postresuscitation functional metabolic damage to the heart]. AB - The experiments on male rats revived after a 4-min clinical death caused by acute blood loss have demonstrated considerable functional and metabolic heart damage in the early rehabilitation period. It should be noted that the leading pathogenetic factors underlying this damage are excessive activation of lipid peroxidation, and enhanced hydrolysis of membrane phospholipids accompanied by arrhythmias, increased permeability of cardiomyocyte membranes, oxidation and phosphorylation disbalance, which is associated with disorders in the energy supply of myocardial contractility function. Preinjection of a synthetic antioxidant oxypyridine-6 at a dose of 50 mg/kg reduces considerably heart damage in the early postresuscitation period. PMID- 1897799 TI - [Clopheline as a component of general anesthesia during surgery in elderly and aged patients]. AB - Clopheline (2-3 micrograms/kg; 2-2.2 micrograms/kg in weak patients) as a component of premedication, for the induction to anesthesia, and in combined endotracheal anesthesia as an analgesic and vegetostabilizing agent has been used in 150 patients, aged 60 to 85 years during planned and emergency surgery. Reduced doses of barbiturates (3 mg/kg) and fentanyl (1.5-2.1 micrograms/kg for the induction to anesthesia and 0.5-0.67 micrograms/kg for analgesia maintenance) were used. At certain stages use was made of droperidol, beginning with a test dose 1.25 mg and not exceeding 5 mg during surgery. The use of clopheline in this category of patients ensures neurovegetative inhibition adequate to the operation stress. In 80% of patients favourable hemodynamic changes have been observed. 20% of patients require droperidol administration at a dose 1.25-5 mg during surgery. Due to low doses, the risk of complication associated with the use of narcotic analgesics in elderly and old patients is reduced considerably. PMID- 1897800 TI - [Anesthesiologic care of infants aged 3 years or less on mass admission of casualties (replacement of fluid and electrolyte deficiencies)]. PMID- 1897801 TI - [Means and methods of non-opiate analgesia from the point of view of the concept of the adrenergic regulation of pain sensitivity]. AB - Nonopiate aspects of analgesia are discussed in brief from the historical point of view. The existence of adrenergic mechanisms inhibiting pain responses has been proved and they were measured by different analgesimetric procedures at the level of cerebral and spinal alpha 2 and alpha 1 adrenoceptors, respectively. A comparative analysis has shown the advantages of clopheline over conventional opiate analgesics. Preliminary clinical trials have demonstrated the efficacy of antinociceptive and hemodynamic effects of clopheline (clonidine) in different pain syndromes. The prospects of clinical application of clopheline-like and other adrenopositive drugs are discussed. PMID- 1897802 TI - [Postoperative prolonged analgesia without the use of narcotic analgesics]. AB - Intravenous prolonged analgesia with analgin, diazepam and no-spa was used in the early postoperative period in 59 patients with acute surgical pathology of the abdominal cavity organs. The technique used ensured a marked analgetic effect. The combination of analgin, diazepam and no-spa, as compared to promedol, promoted to an earlier recovery of the respiration function, which was an effective measure preventing the onset of pulmonary complications. PMID- 1897803 TI - [Analysis of the work of an analgesia service in an outpatient clinic]. AB - The management of patients with chronic pain syndrome in out-patient clinics is a new form of specialized therapy. 347 cancer patients were treated using a modified "analgetic staircase" technique (14% of them at home), with an analgetic effect achieved in 60-70% of cases. The patients with pain syndrome were managed using sacral, epidural and subarachnoidal neurolysis blockades. PMID- 1897805 TI - Guidelines for study of adverse reactions to food. PMID- 1897804 TI - [Live isolated liver cells, their properties and clinical use]. PMID- 1897806 TI - Evaluating the patient with stridor. PMID- 1897807 TI - Recurrent chest tightness in a 28-year-old woman. PMID- 1897808 TI - Comparison between Bricanyl Turbuhaler and Ventolin metered dose inhaler in the treatment of exercise-induced asthma in adults. AB - The aim of the present study was to compare the effect of Bricanyl Turbuhaler (0.5 mg x 1 terbutaline) with the effect of albuterol metered dose inhaler (0.1 mg x 2 albuterol) in patients with reproducible bronchoconstriction. The study was performed as a double-blind placebo-controlled trial in sixteen asthmatic adults. Bronchoconstriction was induced by steady state running on a treadmill. Both 0.5 mg terbutaline and 0.2 mg albuterol have good bronchodilating effects in patients with exercise-induced asthma. There was, however, a faster onset of action after albuterol. The clinical value of this observed difference is uncertain. PMID- 1897809 TI - Occupational asthma due to latex surgical gloves. AB - Since 1979 several reports of contact urticaria due to natural latex have been well documented. Recent case reports suggest that rhinitis and asthma may also be due to rubber exposure. We describe an operating room nurse who was exposed at work to natural rubber (latex) due to the use of latex surgical gloves. After 25 years, she developed contact urticaria, rhinoconjunctivitis and acute asthma following the handling of rubber gloves for surgical purposes. She was symptom free when on vacation. Skin prick testing demonstrated an immediate skin reaction to latex. Rub testing with surgical gloves was positive. Specific IgE antibodies to latex were found by indirect ELISA. Specific bronchial challenge with latex extract elicited an isolated immediate asthmatic reaction that was inhibited with cromolyn sodium pretreatment. Patch testing to common rubber additives was negative. These results suggest that latex present in surgical rubber gloves and probably acting as inhalant allergen may produce occupational asthma in exposed subjects, probably by means of an IgE-mediated mechanism. PMID- 1897810 TI - Safety and possible efficacy of fiberoptic bronchoscopy with lavage in the management of refractory asthma with mucous impaction. AB - Mucous impaction may be suspected in asthmatic exacerbation when, despite aggressive medical management, patients continue to produce sputum containing mucous plugs and exhibit prominent rhonchi and/or wheezes on chest auscultation. Spirometric measurements in this setting corroborate lack of improvement and reveal significant impairment in indices that may reflect small airways function (FEF25-75). We hypothesized that clearance of inspissated secretions by fiberoptic bronchoscopy with lavage (FOBwL) may promote or hasten the clinical improvement of such patients. Fifty-one therapeutic FOBwL were accomplished in 19 patients during 20 episodes of stabilized yet refractory asthma with mucous impaction. No significant complications were encountered. After FOBwL, spirometric measurements of FEV1, FEF25-75, and FVC increased significantly (P less than .01, paired t test), and correlated with relief of dyspnea and mobilization of secretions with cough. FOBwL can be safely performed in stabilized, refractory asthma, and with apparent efficacy. Further investigation is needed to document the therapeutic utility of FOBwL in refractory asthma. PMID- 1897811 TI - Once daily fluticasone propionate aqueous nasal spray is an effective treatment for seasonal allergic rhinitis. AB - A multicenter double-blind, randomized, parallel group study was conducted to evaluate the once daily administration of fluticasone propionate, a potent, new corticosteroid preparation, for the treatment of seasonal allergic rhinitis. Adult patients (n = 227) were treated for 2 weeks with fluticasone propionate aqueous nasal spray 200 micrograms QD or 100 micrograms BID or matching placebo during the autumn pollen season. Overall, the administration of fluticasone propionate once daily in the morning was as effective as the twice daily dosage regimen, and either regimen was more effective than placebo. Improvement in clinician-rated and patient-rated nasal symptom scores, including morning nasal obstruction, was evident within three days of fluticasone propionate therapy and continued throughout the treatment period. Fewer patients receiving fluticasone propionate used rescue medication and had nasal eosinophilia compared with patients receiving placebo. Adverse events were similar in frequency and nature in all three treatment groups. Morning plasma cortisol concentrations and response to cosyntropin stimulation were similar across groups and offered no evidence of HPA axis suppression. We conclude that fluticasone propionate aqueous nasal spray administered once daily is a safe and effective treatment for seasonal allergic rhinitis. The convenience of a once daily regimen may encourage better compliance. PMID- 1897812 TI - Utilizing lung sounds analysis for the evaluation of acute asthma in small children. AB - One of the most difficult aspects of management of acute asthma in the small child is the clinician's inability to quantitate the response or lack of response to bronchodilator agents because of the inability of a child this age to perform objective lung measurements in the acute state. The present study was designed to evaluate bronchodilator responsiveness in children between 2 and 6 years of age with wheezing by means of a computerized lung sound analysis, computer digitized airway phonopneumonography. Children between ages 2 and 6 who were experiencing acute exacerbations of asthma were included in this study population. The 43 children were evaluated by physical examination, pulmonary function testing, if possible, by use of (spirometry or peak flow meter) and transmission of lung sounds to a computer using an electronic stethoscope to obtain a phonopneumograph with sound intensity level determinations during tidal breathing. A control group of 20 known asthmatic patients between the ages of 8 and 52 years who also presented to the office with acute asthma were evaluated similarly. In each of these individuals, a physical examination was followed by complete spirometry as well as computer digitized airway phonopneumonography recordings. Following initial measurements, all patients were treated with nebulized albuterol (0.25 mL in 2 mL of saline). Five minutes after completion of the nebulization all patients were reexamined and repeat pulmonary function tests were performed followed by CDAP recordings. In the study group of children, the mean pretreatment sound intensity level was 1,694 (range 557 to 4,950 SD +/- 745).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1897814 TI - Relationships of total IgE level, skin prick test response, and smoking habits. AB - Epidemiologic observations on 331 men showed that increased serum IgE concentration was associated with a wheal response to skin prick testing, but also to an erythema response in the absence of any wheal, and to heavy smoking. The association between IgE and the various skin prick test responses remained after taking into account smoking and asthma. PMID- 1897813 TI - Use of methotrexate in the treatment of steroid-dependent adolescent asthmatics. AB - Five children 10 to 16 years of age with steroid-dependent asthma were treated with methotrexate. All were able to reduce their doses of prednisone and all had improvement in their clinical status. No significant side effects were noted in patients treated 1 to 3 years. This open study suggests that methotrexate should be considered in the treatment of older children with severe asthma and morbidity from their steroid therapy. PMID- 1897815 TI - Efficacy of ketotifen in corticosteroid-dependent idiopathic anaphylaxis. AB - To assess the potential benefit of ketotifen in the treatment of patients with corticosteroid-dependent idiopathic anaphylaxis, ketotifen was administered in an open trial to nine patients with idiopathic anaphylaxis who required maintenance prednisone for control of their disease. A double-blind trial was not done for reasons of patient safety. After a period of management with prednisone and establishment of the minimal dose of prednisone that controlled idiopathic anaphylaxis, ketotifen was initiated and cautious reduction of prednisone was attempted. The prednisone requirement was not altered in two patients, but prednisone was either substantially reduced or terminated in seven patients. Of these seven, three patients developed recurrent symptoms of idiopathic anaphylaxis after tapering and discontinuation of ketotifen, and ketotifen had to be resumed. The statistical analysis of prednisone reduction was highly significant (P less than .004) and we conclude ketotifen was of significant benefit in seven of nine patients with corticosteroid-dependent idiopathic anaphylaxis. PMID- 1897816 TI - A multicentric study on sensitivity and specificity of a new in vitro test for measurement of IgE antibodies. AB - The sensitivity and specificity of the Pharmacia CAP System, a new in vitro assay for measuring IgE antibodies, were evaluated in a multicentric study on 286 allergic patients and 243 normal subjects. Sensitivity was 95.5%, with results significantly better than RAST for some allergens, and specificity was excellent, 98.1%. PMID- 1897817 TI - Peak nasal inspiratory flow and Wright peak flow: a comparison of their reproducibility. AB - The measurement of peak nasal inspiratory flow (PNIF) is a rapid, convenient, and objective way to assess nasal patency. It is used much less commonly, however, than Wright Peak Flow (WPF), in part, because of concerns about its reproducibility. In order to compare the reproducibility of PNIF with WPF, we obtained multiple measurements of both flows in each of ten healthy, nonsmoking, trained subjects five times throughout the same day and daily throughout the same week. Mean PNIFs (L/min) were 140 immediately after arising, 170 at breakfast time, 183 at lunch time, 170 at dinner time, and 161 at bedtime. Corresponding mean WPFs were 528, 528, 535, 535 and 531 L/min. Peak nasal inspiratory flow coefficients of variation representing minute to minute, hour to hour, and day to day variation were 9.8, 13.5, and 9.7, respectively. Corresponding coefficients of variation with WPF, 2.4, 1.9, and 2.3, were significantly lower. Variability of PNIF and WPF did not increase with increased time spans, suggesting that variation in airway size is less important than variation in technique. Responses to intranasal oxymetazoline, as determined by changes in PNIF and changes in subjective assessments of nasal patency, were then evaluated in ten patients with nasal obstruction. These persons noted a mean subjective improvement of 68% (P = .0002) and demonstrated a mean objective improvement of 21% (P = .05). Posttreatment PNIFs of many individuals who reported substantial subjective improvement failed to exceed the expected variability of the test. This experience fails to demonstrate the utility of PNIF determinations for routine clinical use. PMID- 1897818 TI - [Opportunistic infections in patients after kidney transplantation]. PMID- 1897819 TI - [Psoriatic acropachydermy]. AB - We report the case of a 55-year old man complaining of painful distal changes in the fingers. At physical examination the distal part of the fingers was enlarged as a result of thickening of the soft parts of the ungueal phalanges, and ungueal dystrophies were present. The patient also had inflammatory arthralgia of the distal interphalangeal (DIP) joints, with limited flexion movements. Interrogation revealed a history of cutaneous psoriasis, and radiography of the hands showed DIP arthritis as well as osteitis and periostitis of the ungueal phalanges. The condition was diagnosed as classical psoriatic arthritis of the DIP type, and psoriatic onycho-pachydermo-periostitis, a new form of psoriatic arthritis recently described by Fournie et al. These authors have put forward a physiopathological hypothesis indicating a direct link between psoriatic inflammatory ungueal lesions and lesions of the ungueal phalanx and its soft parts. We had great difficulty in ascertaining the psoriatic nature of this acropachyderma, and we made successive tentative diagnoses of DIP osteoarthritis, pachydermo-periostitis and acromegaly. In this study, we describe the appearance of the ungueal lesions suggestive of psoriasis, and the other clinical forms of psoriatic arthritis. PMID- 1897820 TI - [Sporotrichoid form of M. marinum infection in a patient treated with cyclosporin following kidney transplantation]. PMID- 1897821 TI - [Superficial pemphigus in children. Induction role of amoxicillin?]. PMID- 1897822 TI - [Lichen planus pemphigoides]. PMID- 1897823 TI - [Role and methods of radiotherapy in the treatment of malignant melanoma]. PMID- 1897824 TI - [Arguments against the follicular origin of Verneuil's disease]. PMID- 1897825 TI - [What is your diagnosis? Fissure of the lip attributed to a superficial large caliber artery]. PMID- 1897826 TI - [Focus on tuberculids]. PMID- 1897827 TI - [Acquired syphilis and HIV infection]. PMID- 1897828 TI - [Management of lymphangioma]. PMID- 1897829 TI - [Pemphigus: autoimmune disease, mechanisms of manifestation]. PMID- 1897830 TI - [Pemphigus vulgaris induced by radiotherapy]. AB - A 54-year-old male patient who had been suffering from lymphoma for four years developed pemphigus vulgaris three weeks after exposure to radiotherapy. Skin lesions were initially strictly confined to the irradiated area and later extended over other skin areas. The eruption rapidly improved with glucocorticosteroid therapy which could be stopped after six months. Thirteen cases of pemphigus following X-ray irradiation have been published, twelve of them being associated with an internal malignancy. Clinical data strongly indicate radiation therapy as a provoking factor for the development of pemphigus, but a possible role of the neoplasia in our patient cannot be ruled out. It is suggested that immunological disturbances associated with lymphoma lead to an autoimmune response after exposure to X-rays. Ionizing radiation may alter the antigenicity of the epidermal cell surface or unmask epidermal antigens. PMID- 1897832 TI - [Carcinoma cuniculatum arising in necrobiosis lipoidica]. PMID- 1897831 TI - [Autochtonous leprosy in a patient treated for superficial pemphigus]. PMID- 1897833 TI - [Connective tissue nevus of the disseminated elastic type without osteopoikilosis or Weidman juvenile elastoma]. PMID- 1897834 TI - [Gammel's non-paraneoplastic erythema gyratum repens]. PMID- 1897835 TI - [Atopic cataract. Apropos of a case]. PMID- 1897836 TI - [Epidermolysis bullosa acquisita]. PMID- 1897837 TI - [Bullous pemphigoid and multiple sclerosis]. PMID- 1897838 TI - [Note on the history of syphilology in medieval Poland]. PMID- 1897839 TI - [Do cephalosporins have a role in the treatment of syphilis?]. PMID- 1897840 TI - [What is your diagnosis? Acute hemorrhagic edema in infants]. PMID- 1897842 TI - [Puva therapy and carcinogenesis]. PMID- 1897841 TI - [Is systematic excision of small congenital nevus recommended?]. PMID- 1897843 TI - [Endoscopy of the salivary glands]. AB - The author has developed an original method of exploration of the salivary glands: ultrafine fibroscopy. After briefly describing the equipment, the method and the indications, he demonstrates how it is now possible to extract stones via the natural passages using a miniaturized basket catheter, avoiding the need for more extensive surgery. PMID- 1897844 TI - [Echography of the parotid gland]. AB - Ultrasound is the first choice imaging modality for the evaluation of parotid lesions because of its simplicity and its sensitivity which is as high as that of a CT scan. It can differentiate between benign and malignant tumors. However MRI is necessary for the exploration of the deep lobe, regional spread and a better histopathologic differentiation. PMID- 1897845 TI - [Surgery of the parotid gland. Indications. Review of the anatomy]. AB - The surgical division of the parotid gland in three parts or "lobes" in relation to facial nerve is a practical custom. After revising the surgical anatomy, the indications and operative technique of total parotidectomy with preservation of the facial nerve (TPP) are described. The discussion is open for pleomorphic adenomas of the superficial lobe, between some authors in favour of a superficial parotidectomy and others who perform a systematic TPP. Other surgical operations are total parotidectomy (TP) without preservation of the facial nerve, TP associated with a neck dissection, at lastly extensive or partial parotidectomies. Trans-parotid surgery uses the parotid region as an approach to neighbouring structures or regions. PMID- 1897846 TI - [Maxillary sinusitis disclosing a nasosinusal site of ameloblastoma]. PMID- 1897847 TI - [Sinusal aspergillosis]. PMID- 1897848 TI - [Granulocytic sarcoma. Apropos of a case]. AB - The authors report a case of orbital granulocytic sarcoma complicating a case of acute myeloblastic leukaemia, which was investigated by CT and MRI. CT revealed a moderately contrast-enhanced orbital mass. The MR signal intensity was identical to that of grey matter on T1-weighted sequences and identical to that of white matter on T2-weighted sequences. PMID- 1897849 TI - [Uncommon presentation of thyroid cancer]. AB - Thyroid carcinomas are rare. Papillary carcinomas are the most frequent and preferentially spread via lymphatics. Cervical lymph node metastases are common and may be the presenting sign of the disease, when thyroid carcinoma is occult. PMID- 1897850 TI - [Bilateral giant aneurysm of the carotid siphon]. PMID- 1897851 TI - [Organized follicular cyst simulating a sinus lesion]. AB - Follicular cyst is a frequent lesion rich in cholesterine and methemoglobin. These cysts produce T1 shortening and a high intensity signal on T1-weighted imaging. The most frequent location is the lower mandibular ramus. Sometimes, it occurs in the maxillar with possible involvement of the paranasal sinuses simulating a mucocele or a space-occupying lesion of the sinus. PMID- 1897852 TI - [Lipoma of the parotid gland. Apropos of a case]. AB - Lipoma of the parotid gland is a rather rare tumor (2-3% of all tumors of the gland). Comparative imaging of a case of parotid lipoma by computed tomography, sonography and magnetic resonance is presented. PMID- 1897853 TI - [Normal imaging of facial sinuses]. AB - The high spatial resolution of computed tomography allows visualisation of the fine structures of the facial skeleton and gives precise information about the anatomy of the nasal cavity, the paranasal sinuses and their relations with adjacent structures. A detailed knowledge of the normal anatomy, particularly of the nasal cavity and ethmoid, is very useful to provide to the surgeon with a precise pre operative surgical map, before transnasal endoscopic ethmoidectomy or management of paranasal sinuses tumors. PMID- 1897854 TI - [Facial sinuses. Inflammation]. AB - The radiologist must have a thorough knowledge of the normal anatomy and the pathologic spectrum of the paranasal sinuses to in order determine the location and the extent of abnormality and to plan the surgical approach. We describe the normal anatomy and variations such as concha bullosa which can alter nose physiology. Many examples of congenital and inflammatory lesions affecting this region are described, such as naso-sinus polyposis and congenital or inflammatory lesions. PMID- 1897855 TI - [Maxillofacial injury and x-ray computed tomography]. AB - Facial injuries often occur as a result of cranio-encephalic trauma. They are preferentially studied by CT. In the emergency situation, CT is primarily useful to identify post-traumatic brain damage, which determines the vital prognosis. The study of the orbital apex and temporomandibular joint in the same session provides useful information about the functional prognosis. Further CT studies are required for a complete maxillofacial evaluation. They are usually performed 6 days after the trauma. Coronal and axial thin slices provide a definitive assessment of the bony structures involved. These two CT examinations warrant optimal preoperative planning. PMID- 1897856 TI - [Traumatic pathology of the face]. PMID- 1897857 TI - [Radiologic diagnosis of post-traumatic cerebrospinal rhinorrhea]. AB - It is imperative to identify the cause of cerebrospinal fluid (CSF) leak due to the major risk of infectious complications. Mainly the consequence of a skull base or facial trauma, its most frequent symptom is rhinorrhea. It represents a real diagnostic, clinical and radiological challenge. Two extreme situations raise different problems: either CSF leak is active, with important facial damage involving frontal, ethmoidal or sphenoidal sinuses and petrous bone; in such cases, evaluation by CT is sufficient and easy. Or the leak has dried up, there is no evidence of bony fracture; it is imperative to localize the exact site of the bony or dural defect: CT in axial and coronal planes with thin slices, computerized tomographic cisternography with non ionic water soluble contrast media in order to exhibit the leak in the paranasal sinuses. In some cases however, pitfalls still occur in the determination of such meningeal fistulae. PMID- 1897858 TI - [Benign pathology of the facial bones]. AB - Benign pathology of the facial bones is divided into three groups: congenital, infectious and neoplastic. The knowledge of segmentation of the face into meridians is important for understanding malformations. Panoramic X-rays remain their diagnostic value. CT is able to define the exact location and contents of the tumor. Nowadays, MRI, sometimes gives information concerning the exact contents of tumors. The face is divided into meridians numbered from 0 to 7 and from 8 to 14 counting from the middle part to the external auditory neatus. Infection from dental caries may spread to the maxilla and the mandible and sometimes into masticator spaces. It can be responsible for maxillary fungal sinusitis in tumor. The main problem is not exact diagnosis but the exact location and extent of the disease in order to allow large surgical removal. PMID- 1897859 TI - [Tumors of the facial bones. Current imaging: x-ray computed tomography versus MRI]. AB - This study evaluates the comparative efficacy of MRI and CT in evaluating facial tumors. MRI, with its excellent contrast on T2 weighted and post-gadolinium sequences, is superior to CT for delineating tumor extension, the information essential for appropriate surgical intervention. Both modalities can sometimes be helpful for tumor characterisation. PMID- 1897860 TI - [Malignant granuloma of the mid-face: value of x-ray computed tomography/MRI imaging]. AB - CT an MR imaging are now an integral part of the work-up of every ulcerative lesion of the mid-face. The CT scan enables an exhaustive evaluation of the bone and cartilage necrosis by using bone densitometry settings. The mass lesions, the inflammatory areas and the thickened mucosa are best demonstrated using the tissue densitometry settings. Injection of iodinated contrast material makes clearer delineations of the abnormalities, but doesn't differentiate well between muco-purulent fluid retentions (in the sinuses for example) and solid neoplastic masses. MRI is the technic of choice for this goal; it also gives helpful images in the sagittal and frontal planes. CT and MR imagings are best combined to guide the surgical biopsies and the radiation therapy when managing the difficult problem of mid-face ulcerative lesions. PMID- 1897861 TI - [Endonasal microsurgery]. AB - Endoscopic surgery of the sinuses is a valuable procedure for evaluating allergic or infectious chronic recurrent sinusitis. It allows assessment of the ostium and the state of the mucosa. Its complications are exceptional (rhinorrhoea, meningitis, orbital trauma), but require a detailed preoperative examination in order to reveal variations in sinus anatomy. The role of preoperative CT is therefore to analyse the type and the extent of the disease and individual anatomical variants. It is difficult to predict the depth and angle of introduction of the endoscope on the basis of the CT scan, which is performed in the coronal plane with variable angle. Ideally, only lateral scans would allow guidance of the introduction of the endoscope (hence the value of MRI or 3-D reconstructions). PMID- 1897862 TI - [Radioanatomy of the ethmoid]. AB - The radiological anatomy of the ethmoid was poorly understood until the arrival of tomographic methods, especially computed tomography. Mouret, Professor at the Faculty of Medicine of Montpellier, devoted himself to the study of this anatomical region and proposed a systematic description of the ethmoid. The usual plain X-ray view of the sinuses present certain defects because of bony superimposition. The OM + 20 degrees view of the base of the skull proposed by G. Guillen appears to be the most precise view for the study of the anatomy and physiology of the region, as it coincides with the axis of drainage of the ethmoidal air cells. PMID- 1897863 TI - [Surgery of the ethmoid by the extranasal approach. Techniques]. AB - The extranasal approach to the ethmoid sinus allows good visualisation of lesions in contrast with endoscopy which provides limited visualisation and needs special optical and microscopie instrumentation. The extranasal approach may be achieved via the maxillary sinus by incision in the upper gingivolabial area and resection of the anterior wall. The lateral edge of pyriform aperture and the intersinuso nasal wall can be resected. An other approach can be achieved by resecting a large area of nasal, maxillary and malar bone. The cutaneous incision is paralateronasal or cranial bicoronal. By a large and bilateral upper gingivolabial incision it is possible to use of nose Degloving approach to the ethmoid. PMID- 1897864 TI - [Study of the salivary glands in 1990]. AB - Radiologic examination of the salivary glands can provide clinically useful information that may help to establish the diagnosis and indicate appropriate therapy. US and conventional sialography remain the standard methods of examination for inflammatory diseases and superficial parotid masses. However, CT and MR have allowed a new means of examination of parotid lesions, or of lesions around the parotid gland. MR appears to be the procedure of choice to investigate adenoid cystic carcinoma, recurrence and tumors expanding into the pterygopharyngal space or the sub-tonsillar space. Stenon duct endoscopy is a new imaging and therapeutic procedure to be introduced into the therapeutic strategy in these patients. PMID- 1897866 TI - [Bacterial enterotoxins: structure, mode of action]. AB - The enterotoxins are macro-proteins, produced by enterotoxic bacterial strains acting in the human or animal intestine during digestive infections. In most cases, they induce diarrhoea (associated or not with tissue damage). These molecules differ in their structure and mechanism of action. Some of them (cholera toxin, Escherichia coli LT) activate a cyclase system (adenylate or guanylate cyclase), inducing water and electrolyte flux in the gut. Conversely, others (toxins A and B, Clostridium difficile; Clostridium perfringens enterotoxin; verotoxin), provoke diarrhoea, intestinal damage associated with inflammatory response acting on cellular functions (protein synthesis, permeability to small molecules). Most enterotoxins act via membrane receptors which they specifically recognize on the surface of the enterocyte. PMID- 1897865 TI - [Coliform bacilli which produce cytotoxins: importance in veterinary medicine and public health]. AB - This article reviews published data (October 1st, 1990) on 4 types of cytotoxins produced by animal and human pathogenic strains of E coli, ie, verotoxins, also named Shiga-like toxins, cytotoxic necrotizing factors, haemolysin, and cytolethal distending toxin. The biological and molecular properties are described for each type of cytotoxin, the association of producing strains with animal pathology, and the role of domestic animals as reservoirs of strains pathogenic for man. PMID- 1897867 TI - [Behavioral ecology of the transmission of rabies]. AB - Red fox behavioural ecology was studied in a rabies-enzootic area in order to determine how population size is balanced despite rabies-induced mortality. The results suggest that the red fox rabies virus equilibrium evolves, and is due to the solitary behaviour pattern of the fox which reduces the risk of virus transmission from on territory to another; and to the subsequent autumn dispersal, which allows the local fox population to recover in the space of under a year. The hypothesis is put forward that rabies does not seem to regulate fox population size. There would therefore be no reason to fear a population explosion after oral immunisation of foxes against rabies. PMID- 1897868 TI - [Catheterization of the cerebral ventricles by the rostral method in cattle]. AB - A new means of access to the encephalic ventricles in the cow has been proposed, consisting of the catheterization of the olfactory recess, situated approximately 25 mm under the skin in the frontal region, vertically from a point situated 15 mm laterally from the median plane at the level of a line drawn between the lateral angles of the eyes. Radiographs show that a radioopaque medium can be diffused throughout the cavities on both sides. PMID- 1897870 TI - Detection of African swine fever virus by a biotinylated DNA probe: assay on cell cultures and field samples. AB - African swine fever virus was detected in various samples using a molecular hybridization technique. A fragment located in a constant area of the viral genome was biotin-labelled. This probe, when present at a concentration of 100 ng/ml of the hybridization solution, could detect 10 pg of target DNA immobilized on nitrocellulose with cellular DNA and RNA. The virus was evidenced after being passaged on monkey kidney cells, either 8 h post-inoculation (pi) if the multiplicity of infection (MOI) was at least 1 hemadsorbing unit (HAd) per cell, or 24 h later if the inoculum was diluted up to 10(-3) HAd per cell. When passaged on pig leukocytes with a MOI of 0.1 HAd per cell, the virus was evidenced 12 h pi, or 24 h pi with a MOI of 10(-2) HAd per cell. The probe did not hybridize with another DNA virus passaged on cells, neither did it react with non-infected blood or ham, but did so if African swine fever virus was resuspended with the samples. The spleen from uninfected pig and the lymph nodes from a pig which had died from hog cholera were found to be negative, whereas the spleen from a pig which had died of African swine fever was positive. These samples were also tested with a 32P-labelled probe whose sensitivity was 10-fold higher. A non-radioactive probe could be used both for the sensitive and specific diagnosis of African swine fever and the detection of the virus in an epidemiological survey. PMID- 1897869 TI - [Decrease of the intestinal microflora without consequences for the morphometry and topography of the distal ileum in the mouse treated with antibiotics]. AB - The aim of this study was to assess the possible modifications in the conventional intestine when deprived of its symbiotic microflora. The experiment was designed to study the effect of a heavy antibiotic dose on fecal microflora during the 33-d treatment period as well as its effects upon the intestinal wall. Conventional adult mice received either a casein-starch diet (conventional controls) or an antibiotic-supplemented (0.66% dry matter, DM) diet (treated conventionals); Furthermore, germ-free (axenic) mice taken from isolators to the open animal room received the same antibiotic-supplemented diet (treated axenics) Fecal microbial population remained around 10(8)/g in the conventional mice while it decreased to 10(3)/g in the treated conventional mice. Fecal microbial population of the treated axenic mice dropped to 10(2)/g. At the end of the 33-d treatment period, no significant difference in ileal villus height between the treated or control groups no difference either was seen in the aspects of the villus and cell surface as shown by scanning electron microscopy. In the control group, however, development of bacterial colonies exhibiting various shapes were observed on the intestinal mucus. Although it was found that antibiotic treatment was followed by significant changes in microbial population and biochemical composition of digestive contents, this study concluded that the structure of the distal ileal epithelium was not impaired. PMID- 1897871 TI - Adherence of Pasteurella multocida isolated from pigs and relationship with capsular type and dermonecrotic toxin production. AB - Pasteurella multocida can often be isolated from pneumonic lungs in pigs. There is little information about the pathogenesis of this infection. Attachment of microorganisms to eucaryotic cells is considered to be a prerequisite for colonization of the host in the pathogenesis of bacterial infections. Forty-seven P multocida strains isolated from pigs in France, and belonging to capsular type A or D were tested for their ability to agglutinate human erythrocytes, and to adhere to tracheal and lung cells. Each isolate was tested for dermonecrotic toxin production. Adherent strains were further observed by electron microscopy to look for attachment structure. Only type A strains agglutinated human O erythrocytes, but no relationship was observed between hemagglutination and dermonecrotic toxin production. The results of the adherence tests showed a greater affinity (P less than 0.05) of type A strains for lung cells (50% were adherent, whereas only 20% of type D strains were adherent) but did not reveal any correlation between adherence and the presence of dermonecrotic toxin. Microscope observations showed that these P multocida strains did not possess any pili-like structures. In conclusion, by means of the adherence test we were able to demonstrate a stronger adherence of type A strains and this adherence did not seem to be related to pili-like structures. PMID- 1897872 TI - [Seasonal variations of Fasciola hepatica infection in goats in the area of Haouz (Morocco)]. AB - The prevalence and level of infection with Fasciola hepatica were assessed monthly over a 12-month period in goats slaughtered in the Haouz area, in correlation with the dynamics of Lymnaea truncatula populations. The infection rate was high in winter (23.8%) in January), and summer (17.1% in August), and relatively low in spring and at the beginning of autumn. The infected animals had a fluke burden range of 1-48; a mean of 13 was recorded in July. Lymnaeid snails were observed in their habitat throughout the year, but were more abundant during the hot months (July and August). Snails infected with F hepatica were found in February, June, July and August; their infection rate did not exceed 3%. These data enabled us to hypothesize that the main periods for transmission of fascioliasis were spring and fall; however, potential infections during other periods of the year were possible. The susceptibility of goats to infection with F hepatica appears to be similar to that reported in sheep. PMID- 1897873 TI - Metabolic changes in the rumen following protozoal inoculation of fauna-free sheep fed a corn silage diet supplemented with casein or soybean meal. AB - Fauna-free wethers were fed bi-hourly a corn silage diet containing casein or soybean meal as a protein supplement. The wethers were inoculated via rumen cannula with a mixed population of ruminal ciliate protozoa. Ruminal fluid was sampled daily for 4 d before and for 13 d (and on d 28) after inoculation. Protozoal populations reached peak numbers on d 8 and decreased to new levels after d 9 for wethers on both supplements. Protozoa decreased (P less than 0.01) the concentrations of total volatile fatty acids, increased (P less than 0.01) the pH and decreased (P less than 0.01) he concentrations of total and non ammonia nitrogen in ruminal fluid. The concentrations of ammonia nitrogen increased with increasing numbers of protozoa for wethers on both supplements, but the concentrations decreased after d 7 to approximately pre-inoculation levels for the casein-supplemented diet. The increasing numbers of protozoa were associated with the increased concentrations of total and free alpha-amino nitrogen (P less than 0.01) and sulfide (P less than 0.05) and with the decreased concentrations of soluble Cu (P less than 0.05) in the ruminal fluid in soybean meal-supplemented wethers but not in those receiving casein. It was concluded that dietary proteins with differing physical characteristics are metabolized to a different extent by ruminal ciliate protozoa, which in turn can affect the metabolism of other dietary nutrients such as nitrogen and sulfur and contribute to copper-sulfur interaction. PMID- 1897874 TI - Muscle injuries, their healing process and treatment. AB - Muscle injuries represent one of the most common traumas in sports medicine. They have different clinical manifestations depending on the trauma mechanism: laceration, contusion and strain. The range of lesions varies from minor partial ruptures to complete ruptures of the muscle. The muscular tissue has a capacity to regenerate and the healing process consists of regeneration of muscle fibres and formation of a connective tissue scar. The healing is also greatly dependent on the ingrowth of vascularity and regeneration of intramuscular nerve branches. Immobilization and mobilization have a notable impact on the recovery, the former being of importance initially by reducing the size of injury and the latter later on by inducing greater granulation tissue production. Mobilization treatment is also a prerequisite for intensive muscle fibre regeneration and better preconditions to achieve the original tensile properties of the muscle. Surgical intervention is occasionally needed in complete ruptures to evacuate the haematoma or to suture the ruptured ends of the muscle to apposition. PMID- 1897875 TI - Epidemiology and prevention of skiing injuries. AB - Between 1972 and 1987, the authors prospectively evaluated all 5701 injuries which were reported to the injury clinic operating in the base lodge of a ski area in northern Vermont, USA. During that time approximately 1,690,000 skier visits were estimated to have occurred at the ski area. The total injury population was divided into 28 groups and sub-groups and examined by regression analysis for long term trends. Among upper body injuries, only lacerations showed a positive improvement. Among lower extremity injuries, virtually all injuries below the knee improved dramatically, some groups by more than 80%. Knee injuries, although improved as a group, showed a marked 2.7-fold increase in serious (third degree) sprains usually involving the anterior cruciate ligament. Clavicular fractures were the only upper extremity injury which increased significantly in incidence. PMID- 1897876 TI - Knee injuries, a major problem in sports medicine: past, present and future. PMID- 1897877 TI - Clinical diagnosis of acute knee ligament injuries. PMID- 1897878 TI - Ultrasonographic possibilities and findings in most common sports injuries. AB - It is known that sports, especially competitive sports, can cause different kinds of injuries, which can be fractures and/or dislocations of joints, but more often soft tissue lesions. As a rule it is difficult to establish clinically the character and/or size of the sports lesion, but nowadays we have methods to examine soft tissues. The most modern method is Magnetic Resonance Imaging (MRI), but the cheaper one is ultrasound examination, which is some years old but has been developed continually. Recent studies have shown that soft tissue sports injuries can be diagnosed quite easily. The lesions can be localized and their size determined, parametres especially useful if surgery is required. We conclude from our studies that ultrasonic soft tissue examination improves diagnostic accuracy of sports injuries. Recovery is faster thanks to correct diagnosis and treatment. The healing process can also be followed up by ultrasonography. PMID- 1897880 TI - Arthroscopic anterior and posterior cruciate ligament reconstruction technique. PMID- 1897879 TI - How to treat knee ligament injuries? AB - Indications for conservative treatment of knee ligament injuries can be established for all grade I or II sprains (partial tears), as well as isolated grade III sprains (complete tears) of the posterior cruciate ligament (PCL) and medial collateral ligament (MCL). These injuries should be treated with immediate mobilization. Only in isolated partial anterior cruciate ligament (ACL) tears without a positive pivot shift phenomenon is conservative treatment justified. However, many of these injuries may require operative reconstruction later. In complete ACL tears the surgical treatment consists of primary reconstruction or augmented primary repair. Today, the middle third of the patella tendon with the bone blocks is regarded as the "gold standard" for augmented repairs and late reconstructions. For the present, there is no place for synthetic prostheses in the treatment of an acute ACL rupture. Allograft replacement of the ACL must now be considered an experimental procedure. In the reconstruction of the PCL the above mentioned patella tendon graft is also preferable. Lateral collateral ligament (LCL) tears, especially if they are combined with ruptures of posterolateral ligament complex, should be repaired immediately after the injury. In these injuries late reconstructions are difficult and the results are poor. Conservative treatment of partial tears and postoperative treatment of reconstructed ligaments is twofold: on the one hand, the healing tissue should be protected and on the other hand, atrophy and wasting of uninjured tissue should be avoided. Overload and stretching of the injured ligaments should be eliminated with the aid of a suitable knee brace, but early range of motion exercises of the knee are allowed immediately.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1897881 TI - Synthetic materials for the replacement of knee ligaments. AB - The augmentation of autogenous tissue should be considered in failed autogenous grafts or when inadequate tissue is present which does not allow adequate tissue length, provide enough tensile strength, or insufficient fixation. Multiply failed anterior cruciate ligament surgical procedures should be considered candidates for a true prosthetic replacement. In certain patients with degenerative changes and functional instability, the use of a true prosthesis might also be considered in combination with other types of degenerative joint surgery. With all of our attempts at ligamentous reconstruction about the knee, we are seeking the ideal solution--the ultimate surgical technique for the anterior cruciate loss--minimal morbidity, rapid rehabilitation, return to full function, and reliable results. The intra-articular notch is not the ideal area to create a new ligament whether it be by autogenous or artificial means. PMID- 1897882 TI - Acromioclavicular joint injuries and their management principles. PMID- 1897883 TI - Consideration and management of rotator cuff tears in athletes. PMID- 1897884 TI - Ankle ligament injuries and operative treatment principles. PMID- 1897886 TI - Achilles tendon injuries in athletes. AB - During 1976-1986, 3,336 athletes consulted the Turku Sports Medical Research Unit, 455 (14%) of these for Achilles tendon injuries. Achilles tendon problems were more frequent among joggers (66%), tennis players (32%) and runners (24%), which emphasizes the aetiological role of running. Achilles tendon complaints (n = 698) consisted of paratenonitis (including tendinopathies) (66%), insertional (23%) and myotendineal (8%) pain syndromes and total tendon ruptures (3%). The mean age of Achilles tendon injury patients was 26.1 years; among other sport injury patients it was 21.9 years (P less than 0.001). Surgery was performed in 24% of the subjects with paratenonitis and insertional pains. Different structural faults were found in 60% of the athletes with Achilles tendon overuse injuries. Forefoot varus correlated (r = P less than 0.001) with paratenonitis. A markedly limited total passive subtalar joint mobility and/or ankle joint dorsiflexion with knee extended was found in 6% of the conscripts, in 44% of the control athletes and in 58% and 70% of athletes with Achilles tendon paratenonitis and insertional pains, respectively. The range of motion of the ankle and subtalar joints was much lower in athletes than conscripts (P less than 0.001). PMID- 1897885 TI - Diagnosis and treatment of delayed and non-union stress fractures in athletes. AB - Stress fractures in athletes usually heal well with merely rest and conservative treatment. It has been estimated that in Finland 400-500 athletic stress fractures occur annually per year. In sports clinic series stress fractures comprise 3.3 to 4.6 per cent of all overuse injuries. Delayed and non-union have been reported to occur in athletes quite often, up to 10 per cent of athletic stress fractures in Finland. The reason is on the one hand delayed diagnosis due to late consultation of expert physicians, and on the other hand too short a rest from hard physical activity. Delayed and non-union are most often seen in the hallux sesamoids, mid-tibial staft, base of fifth metatarsal, tarsal navicular and olecranon. The pars articularis of the fourth and fifth lumbar vertebra is a site of stress fracture and spondylolysis. In this report the diagnosis, symptoms and findings as well as the operative treatment of these overuse injuries is discussed. PMID- 1897887 TI - Overuse injuries of the Achilles tendon. AB - Among the 4,020 athletes (males 73%, females 27%) treated at the Department of Sports Medicine of the Deaconess Institute, Oulu, Finland in the period 1986-1989 there were 273 athletes with 330 of instances Achilles tendon overuse. Peritendinitis, tendinitis, partial rupture, retrocalcanear bursitis and insertiotendinitis were the most common diagnoses. Acute and subacute ailments were usually treated successfully by conservative means. 45.5% of the overuse injuries became chronic, failed to respond to conservative treatment and were treated surgically. The results were excellent or good in 86% of those operated on for chronic peritendinitis. The overall results were good in 69.3% of the patients. PMID- 1897888 TI - Operative treatment of typical overuse injuries in sport. AB - In this report 670 operations, performed in 643 patients were analyzed. The indication for the surgery was a chronic symptomatic overuse injury caused by sports and physical activity. 552 (82.4%) of the operations were performed in men and 118 (17.6%) in women. The mean age of the patients was 24 years. Almost 90 per cent of the patients had presented following competitive sports and ten per cent recreational sports. More than 91 per cent of the operations were performed for lower extremity problems. The knee, foot and ankle regions needed surgical treatment most often in this series. Tendon and tendon sheath operations formed the majority (32%) of the operations. Chronic Achilles tendon problems (159) formed the biggest group of the diagnoses. Chronic overuse injuries do not respond always to conservative treatment. Surgery is often needed in the final stage of an overuse injury. The results of these operations are good. PMID- 1897889 TI - The hamstring syndrome--a new gluteal sciatica. AB - The condition in which pain is felt over the area at the ischial tuberosity and radiating down the back of the thigh is labelled the hamstring syndrome. The pain is typically incurred by assuming a sitting position, stretching the affected leg or/and running fast. The symptoms are caused by tight, tendinous structures of the hamstring muscle at the area of its insertion into the ischial tuberosity. Following division of these structures, complete relief is obtained. PMID- 1897890 TI - The medial tibial syndrome. AB - The medial tibial syndrome is the most common overuse injury, which occurs at the inner border of the shin, mostly in the lowest and middle thirds. It is characteristically a chronic compartmental syndrome and its treatment is fasciotomy if conservative management to allow healing fails. PMID- 1897891 TI - Patellofemoral problems in sports medicine. PMID- 1897892 TI - Operative management of patellofemoral pain. AB - In short, the surgical treatment of patients with patellofemoral pain will depend on understanding each specific disorder and the pattern of articular degeneration. Tilt alone generally responds well to lateral release. Subluxation, particularly when more severe, may require medial imbrication and/or a distal (Trillat) procedure in addition to lateral release to achieve extensor mechanism balance. When there is significant patellar arthrosis, an oblique osteotomy deep to the tibial tubercle will permit unloading of the patellar articular surface in addition to realignment. A small amount of metaphyseal bone placed in this oblique osteotomy will permit straight anterior displacement of the tibial tubercle of 15-20 mm with minimal bone graft when necessary. These basic surgical procedures will permit adequate treatment of most patients with resistant patellofemoral pain (with or without arthrosis) when non-operative measures have failed and the appropriate procedure is selected for a specific mechanical disorder. PMID- 1897894 TI - Sports injuries. PMID- 1897893 TI - The effect of bracing and taping in sports. AB - There has been an increase in the use of bracing, and to some extent taping during the last decade. The sports medicine community has not only developed a greater interest in the prevention of injuries, e.g. ligament injuries to the knee and ankle, there has also been an interest in an early return of the injured athlete to sports after both operative and non-operative treatment programs. This interest, coupled with the injured athlete striving to return to his/her original sport at the same intensity level, has challenged the limits of joint support provided by bracing and taping. The purpose of this paper is to review the biomechanics of bracing and taping as they apply to both the knee and ankle joints. PMID- 1897895 TI - Sports traumatology expands the art of surgery. PMID- 1897896 TI - Sports traumatology today. A review of common current sports injury problems. AB - Increasing participation and training intensity in sports and physical activity has resulted in an increasing number of injuries as well as recognition of "new" injuries. Improved diagnostic techniques such as MRI, CT scan, scintigraphy and ultrasound have proven to be valuable in the diagnosis of especially soft tissue injuries. Surgery is today generally accepted as the treatment of choice for anterior cruciate ligament injuries in the active population. Arthroscopic reconstruction using the bone-patellar tendon-bone graft is considered to be the "gold standard". Alternative grafts such as semitendinosus and gracilis can also be used. The use of artificial ligaments and allografts is still experimental. Most posterior cruciate ligament injuries are today treated conservatively, and so are ankle ligament injuries. There is still no final solution how to treat articular cartilage lesions although interest is being focussed on cartilage resurfacing. Overuse tendon injuries often become chronic and are then associated with persistent structural alteration. Chronic overuse injuries are characterized by a failure to develop adequate scar tissue restoration. The reason for this delayed healing is still unclear. The treatment of these injuries include, today, early strength and stretching training, but the main concepts are still controversial due to lack of scientific evidence. Our understanding of shoulder injuries in athletes has developed enormously during the last few years. The use of arthroscopy when performing subacromial decompression and surgery of labral tears have allowed more athletes to return early to sports than before. Laboratory studies have increased our understanding of muscle injuries and they show the importance of early mobilization. Prevention will be a major issue for research within the next decade. It is the author's opinion that within the next decade, sports traumatology will take a leading role in orthopaedic and sports medicine research. PMID- 1897897 TI - Occurrence and epidemiology of sports injuries in Finland. AB - The popularity of different sports activities has increased during the last three decades, a development that has been considered beneficial in many respects for society as well as the individual. One of the deleterious effects of this development, however, is an increased number of sports injuries. The exact incidence of sports injuries is difficult to calculate due to many potential biasing circumstances like data collection, definition of sports injuries and the lack of suitable control subjects. In a large study where the acute accidents in Finland were examined the incidence of sports injuries was 670/10,000 inhabitants in 1987. Seven per cent of the total number of injuries seen at a large casualty department were sports injuries. The main purpose of studying sports injuries is to identify the sportsmen at high risk of injury and the main risk factors. Only in this way can preventive measures be undertaken in an effort to make participation in sports safe, regardless of the level or type of sports practiced. PMID- 1897898 TI - Food patterns in the European past. AB - This paper presents in an intellectually very shortened form the most important developmental stages of diet since the beginning of mankind. The relations in central Europe and the structural change of eating habits under the influence of industrialization and urbanization and the various connections to health in the last 200 years are particularly discussed. PMID- 1897899 TI - Cholesterol-lowering effect of the mushroom Pleurotus ostreatus in hereditary hypercholesterolemic rats. AB - We studied the effect of the edible mushroom Pleurotus ostreatus (4% in diet containing 1% of cholesterol) on serum and liver lipids in female rats with hereditary enhanced sensitivity to alimentary cholesterol. We found that the consumption of the mushroom-containing diet prevented serum cholesterol increase which was manifested at the end of the 4th week of the experiment. At the end of the 7th week of the experiment the cholesterolemia was lowered by almost 40% as compared with control animals kept on the same diet but without the mushroom. The decrease in serum cholesterol levels is a consequence of the decreased cholesterol concentrations of very-low-density lipoproteins and of low-density lipoproteins. PMID- 1897900 TI - Chromium and cholesterol-induced atherosclerosis in rabbits. AB - Thirty-three rabbits on a cholesterol-enriched diet were randomized into 6 groups and treated with daily injections of either water, 20 micrograms of potassium chromate or 1, 5, 10 or 20 micrograms of chromium chloride, respectively, for 135 days with a 2- to 10-fold increase in serum chromium. There was a marked reduction in the percentage of aortic intimal surface covered by plaque, in aortic weight and cholesterol content in the treated animals. Rabbits treated with 20 micrograms of chromium chloride showed a better response than those treated with either 10 or 20 micrograms of potassium chromate. PMID- 1897901 TI - Whole-body autoradiography in rats after intravenous administration of L-alanyl-L [U-14C]glutamine. AB - The uptake and distribution in rats of the radiolabelled dipeptide L-alanyl-L-[U 14C]glutamine were investigated by whole-body autoradiography. Rats were killed 5, 30 and 180 min following bolus injection of the peptide via the tail vein and, as a comparison, 180 min after injection of [U-14C]glutamine; 30-microns sections of the animals were autoradiographed against an X-ray film. Tissue specimens from the remainder of the carcass were completely combusted and the 14CO2 formed was analyzed by liquid scintillation counting. Visceral organs especially exocrine glands and the mucosa of the alimentary tract showed an initially high labelling (5 min), whereas skeletal muscle and brain exhibited maximum radioactivity 30 min after peptide bolus. Muscle and intestine (19 and 10% of the dose injected, respectively) showed the highest 14C incorporation of all tissues investigated. The broad conformity in 14C distribution observed after peptide and glutamine bolus strongly indicates similar utilization of free and peptide-bound glutamine. PMID- 1897902 TI - Effects of dietary cholesterol and phytosterol overload on Wistar rat plasma lipids. AB - To study the effects of dietary phytosterols on plasma cholesterol, Wistar rats were fed diets containing a cholesterol overload (24 mg/day), to which phytosterols were added or not (24 or 96 mg/day). The cholesterol overload led to a marked increase in cholesterol, mainly linked to very-low-density and low density lipoproteins. Phytosterols reduced those effects, the highest dose being most efficient. No undesirable effect was observed either on body or on liver weights. This shows that low doses of phytosterols are sufficient to significantly decrease a plasma cholesterol enhancement induced by a dietary cholesterol overload. PMID- 1897903 TI - Effect of oxysterol-enriched low-density lipoprotein on endothelial barrier function in culture. Low-density lipoproteins. AB - High levels of plasma low-density lipoproteins (LDL) are known to be a risk factor for developing coronary artery disease although the specific mechanism involved is unknown. It may be related to effects of oxidized lipid components of LDL on vascular endothelial barrier function (EBF). This study addressed the hypothesis that LDL-associated products of cholesterol oxidation, oxysterols, decrease EBF resulting in increased penetration of blood components such as LDL into the arterial wall. LDL from human volunteers and rabbits was enriched with cholesterol or cholestan-3 beta,5 alpha,6 beta triol (Triol) by in vitro incubation. Exposure of cultured vascular endothelial cell monolayers to LDL enriched with Triol reduced EBF, measured as an increase in transendothelial albumin transfer, whereas cholesterol enrichment, like un-enriched LDL, had no effect on EBF. In a second experimental series, rabbits were gavaged with 100 mg of cholesterol or Triol/kg body weight, and LDL was isolated from serum 24 h after gavage. As was seen with the in vitro experiments, Triol-enriched LDL markedly decreased EBF. Similarly, LDL from cholesterol-gavaged rabbits reduced EBF, while LDL from vehicle treated rabbits had no effect. These results suggest that LDL-associated oxysterols are detrimental to normal barrier function of the vascular endothelium. Disruption of this barrier function may serve as an initiating factor in atherosclerotic lesion formation. PMID- 1897904 TI - Reciprocal responses to exercise in hepatic ketogenesis and lipid secretion in the rat. AB - The effects of 4 weeks of voluntary exercise (rotating wheel) on serum and liver lipid levels were studied in 6-week-old male Wistar rats. The hypotriglyceridemic effect of exercise was not influenced by the dietary fat levels (4.5 and 14.5%), whereas the hypocholesterolemic effect was higher in a low-fat diet than in a high-fat diet. Although the serum cholesterol-lowering effect of exercise was marginal, the beneficial effect on hepatic lipids was observed only in rats fed a high-cholesterol diet. The hepatic contribution to the serum lipid-lowering action of exercise was examined in the isolated perfused livers of rats fed a low fat diet. The reduction (34%) of serum triglyceride by exercise corresponded to the decrease (32%) in the hepatic triglyceride secretion rate, indicating a significant role of the liver in the hypotriglyceridemic effect of exercise. In contrast, the decrease (31%) in serum total cholesterol was considerably greater than that (23%) in the hepatic secretion, suggesting an extra-hepatic contribution. On the other hand, the hepatic production of ketone body was increased by exercise. These results indicate that the altered hepatic partition of long-chain free fatty acids between esterification and oxidation is one of the causative factors for the serum lipid-lowering effect of exercise. PMID- 1897905 TI - Postnatal development of plasma amino acids in hyperphagic rats. AB - The effect of feeding a highly palatable high-energy cafeteria diet on individual amino acid levels in plasma during postnatal development of the rat has been evaluated and compared to chow-fed controls. The cafeteria diet selected by the rats was hypercaloric and hyperlipidic, with practically the same amount of carbohydrate as the control diet, and slightly hyperproteic. In response to cafeteria feeding, significant decreases were observed in plasma serine and cysteine along the period studied. Significant changes with age during the growth period were shown by cafeteria-fed animals, which were not observed in control rats. Citrulline levels were lower on days 10 and 14 in cafeteria pups than in chow pups. Methionine was highest on day 30. Threonine was also higher at days 20 and 30, as was valine but with a nadir at day 10. Lysine showed maximal values on days 14 and 30. PMID- 1897906 TI - Platelet-activating factor in stroke and brain injury. AB - Platelet-activating factor, an endogenous phospholipid of proinflammatory, hemostatic, and vasoactive properties, is synthesized by neurons and in injured brain. Platelet-activating factor is released together with eicosanoids such as thromboxane A2, prostacyclin, and leukotrienes. Its effects in neurons are mediated through a specific receptor coupled to phospholipase C and phosphoinositol metabolism. The cerebrovascular effects of platelet-activating factor include disruption of the blood-brain barrier, edema formation, and vasospasm. It has also been described to possess direct toxicity to neuronal cells in culture. Discovery and development of several highly potent and selective antagonists to platelet-activating factor receptors facilitated experimental studies underscoring the role of this factor as an endogenous mediator in cerebral disorders, particularly cerebral ischemia and trauma. Significant biochemical, microvascular, functional, and behavioral recovery has been demonstrated using these antagonists in an array of experimental models of focal and global ischemia in the central nervous system (CNS). Clearly, studies of platelet-activating factor in experimental models of CNS ischemia and reperfusion injury open a new perspective on phospholipid metabolism in stroke and offer an exceptionally promising therapeutic prospect. Data supporting this factor as a mediator of specific pathological sequelae in stroke and neuroinjury are surveyed in this review. We discuss the mechanisms and significance of platelet-activating factor-mediated effects and propose directions for future studies. PMID- 1897907 TI - The spectrum of lissencephaly: report of ten patients analyzed by magnetic resonance imaging. AB - Clinical data and magnetic resonance imaging scans from 10 patients with lissencephaly were reviewed. Although 6 of the 10 patients were less than 1 year old at the time of their most recent examination, those who were old enough for developmental assessment were, with a single exception, severely developmentally delayed. All patients had anatomical features compatible with impaired neuronal migration but normal myelination and, consequently, adequate glial migration. The severity of the lissencephaly did not seem to correlate with the severity of the clinical manifestations. One patient showed less delayed development than anticipated, perhaps because the most severely involved region of the brain was the prefrontal area. PMID- 1897908 TI - Presence of the terminal complement complex (C5b-9) precedes myelin degradation in immune-mediated demyelination of the rat peripheral nervous system. AB - In this study, the terminal complement complex C5b-9 (TCC) was localized by immunocytochemistry at different clinical stages of experimental autoimmune neuritis. Deposits of TCC were found on the surface of Schwann cells and their myelin sheaths, and to some extent in the extracellular space at predilective sites of impending demyelination before onset of clinical signs and for a short period thereafter. Additionally, TCC was deposited on the surface of W3/13 positive leukocytes. No TCC immunoreactivity was seen in the distal stump of transected sciatic nerves 1 to 15 days after axotomy. The early and transient deposition of TCC on Schwann cells and myelin sheaths in experimental autoimmune neuritis before overt demyelination suggests that complement activation plays a pathogenic role in the initiation of immune-mediated myelin damage. The lack of TCC immunoreactivity after nerve transection excludes a nonspecific activation process. The signals involved in local TCC formation in demyelinating peripheral nervous system disorders have yet to be explored. PMID- 1897909 TI - Presynaptic and postsynaptic striatal dopaminergic function in neuroacanthocytosis: a positron emission tomographic study. AB - Using [18F]dopa, [11C]raclopride, C15O2, and positron emission tomography, we have assessed striatal dopamine storage capacity, dopamine D2-receptor integrity, and regional cerebral blood flow, respectively, of 6 patients with neuroacanthocytosis. The patients with neurocanthocytosis all had chorea and variable combinations of seizures, dementia, axonal neuropathy, and orolingual self-multiation. [18F]dopa positron emmission tomographic findings were compared with 30 normal controls and 16 patients with sporadic, L-dopa-responsive, Parkinson's disease. Caudate and anterior putamen [18F]dopa uptake were normal in patients with neuroacanthocytosis, but mean posterior putamen [18F]dopa uptake was reduced to 42% of normal, similar to that in patients with Parkinson's disease. In patients with neuroacanthocytosis, mean equilibrium caudate: cerebellum and putamen: cerebellum [11C]raclopride uptake ratios were reduced to 54% and 62% of normal, compatible with a 65% and 53% loss of caudate and putamen D2-receptor-binding sites, respectively. Striatal and frontal blood flow was also depressed. The severe loss of D2-receptor-bearing striatal neuron, with concomitant loss of dopaminergic projections from the nigra to the posterior putamen, is consistent with both chorea and extrapyramidal rigidity being features of patients with neuroacanthocytosis. PMID- 1897910 TI - Does tremor pace repetitive voluntary motor behavior in Parkinson's disease? AB - In patients with Parkinson's disease and in normal subjects, the influence of tremor on repetitive voluntary movement was investigated in the index finger by comparing frequency of isometric force tremor with frequency of voluntary alternating isometric contractions. Tremor frequency, measured over the range from 0 to 70% maximum voluntary force, usually increased with force. The tremor frequency band was lower and more often overlapped with the upper voluntary frequency range in patients than in normal subjects. Normal subjects could accurately produce voluntary contractions at all cue frequencies from 1 to 5 Hz. Patients could produce auditory-paced frequencies of 1 and 2 Hz, but at higher cue frequencies, their voluntary contractions were often faster or slower than the cue. The faster or "hastened" voluntary frequencies were within the tremor frequency band, whereas the slowed voluntary frequencies were below it. Maximal voluntary frequency was often greater than the lowest but always less than the highest tremor frequency. It is concluded that parkinsonian tremor may pace voluntary repetitive movements to go faster than intended with the highest tremor frequency being an upper limit for voluntary frequency. Similar mechanisms may underlie the hastened repetitive vocal responses that were also observed in the parkinsonian patients. PMID- 1897911 TI - Lyme neuroborreliosis: a new sensitive diagnostic assay for intrathecal synthesis of Borrelia burgdorferi--specific immunoglobulin G, A, and M. AB - An antibody capture enzyme-linked immunosorbent assay was developed to measure directly intrathecal immunoglobulin (Ig) G, A, and M synthesis specific for Borrelia burgdorferi. Purified, biotin-avidin-peroxidase-labeled B. burgdorferi flagella was used as test antigen. Paired cerebrospinal fluid and serum specimens from 100 patients with clinically definite neuroborreliosis and 35 control subjects with neurological diseases were examined. Significant B. burgdorferi specific intrathecal IgG, A, and M production was found in 89%, 65% and 67% of patients with neuroborreliosis. Local synthesis of specific IgA was only seen in patients with significant local IgG synthesis. Antibody production in cerebrospinal fluid began by 2 weeks after onset of neurological symptoms. At the end of the second week specific IgM, IgG, or both, was detected in 88% of the patients. Specific IgG synthesis was present in all patients by 6 weeks after onset. Specific local IgM synthesis usually disappeared by 3 to 6 months after therapy, whereas specific IgG synthesis persisted after recovery. Even in patients with a severely altered blood-brain barrier, the assay discriminated between intrathecal antibody synthesis and antibody leakage from serum. The assay makes diagnostic measurement of B. burgdorferi-specific intrathecal antibody synthesis reliable, rapid, and accessible as a routine serological test. PMID- 1897912 TI - Asymmetrical ocular pursuit with posterior fossa tumors. AB - We report two patients with posterior fossa neoplasms who demonstrated asymmetrically impaired horizontal ocular pursuit documented with electrooculography. One patient had impaired pursuit contralateral to a pontomedullary lesion, whereas the second patient had impaired pursuit ipsilateral to a pontocerebellar lesion. These patients demonstrate that posterior fossa lesions may impair ocular pursuit either contralaterally or ipsilaterally unlike cerebral hemispheric lesions, which impair ocular pursuit ipsilaterally or bilaterally. PMID- 1897913 TI - Paravermal infarct and isolated cerebellar dysarthria. AB - A patient with isolated cerebellar dysarthria is reported. Computed tomography showed a small infarct in the left paravermal zone of the rostal cerebellum (lobulus simplex and semilunaris superior) in the territory of the medial branch of the superior cerebellar artery. This patient demonstrates the important role of this area of cerebellum in the control of voice. PMID- 1897914 TI - Impaired critical flicker frequency in recovered optic neuritis. AB - Thirteen patients with optic neuritis who recovered normal visual acuity and kinetic perimetry all showed impairment of foveal critical flicker frequency, a psychophysical test of visual temporal resolution. Because the magnocellular visual system demonstrates higher temporal resolution than the parvocellular system, this finding implicates involvement of axonal projections of magnocellular retinal ganglion cells in recovered optic neuritis. PMID- 1897915 TI - MEG versus EEG localization test. PMID- 1897916 TI - Diagnosis of amyotrophic lateral sclerosis. PMID- 1897917 TI - Intraventricular interferon treatment for subacute sclerosing panencephalitis. PMID- 1897918 TI - 116th annual meeting of the American Neurological Association. September 28 October 2, 1991, Seattle, WA. Abstracts. PMID- 1897919 TI - Nursing care classification: a conceptual model. AB - Economic constraints, the information explosion, and advancement of scientific theories have resulted in the need for nurses to document their unique contribution to health care through validation of nursing resources consumed by patients. However, various classification systems have not predicted nursing resources well. This study reviews the theoretical frameworks, reliability, validity, and utility of nursing acuity and severity systems. It proposes a conceptual model for a new nursing classification system to be used for the validation of nursing resources, as the basis of a reimbursement system for nursing services, and for multiple practical and theoretical applications. PMID- 1897920 TI - Problems of nursing home residents: nurse and resident perceptions. AB - The nurse's consideration of the nursing home resident's perspective of his or her problems conveys respect for the resident as an individual and as a valued source of information concerning his or her own needs. Such consideration facilitates mutual setting of goals for patient achievement. The purpose of this study was to determine the similarities and differences between the nurse's perception of the nursing home resident's problems and the resident's perception of his or her problems. Thirty-one residents and their nurses completed questionnaires to identify perceived needs for assistance with daily activities and to assess the presence and degree of specified common problems. Out of 45 items, significant differences between nurse and resident ratings were found for the following 7 items: assistance needed for bathing and grooming, appetite problems, loss of bladder control, difficulty breathing at rest, decreased sense of smell, and loss of usefulness. Implications for nursing practice and nursing staff education are discussed. PMID- 1897921 TI - Preferences for spiritually related nursing interventions among terminally ill and nonterminally ill hospitalized adults and well adults. AB - The purpose of this study was to determine terminally ill and nonterminally ill hospitalized patients' preferences for spiritually related nursing interventions and to identify differences between the two groups. Additionally, preferences of well adults were examined in comparison to the hospitalized groups. Clinical knowledge in nursing as well as empirical work provided background for the study. Three hundred adults participated in the study by responding to structured and open-ended questions about specific nursing interventions that they thought would help meet their spiritual needs. Significant differences were found across the groups, including a higher preference for more direct, spiritually related nursing interventions and more negativity about the nurse's role in caregiving as expressed by the nonterminally ill group. PMID- 1897922 TI - Assessment of hope in psychiatric and chemically dependent patients. AB - Hope is recognized as a healing force, but has not been studied in some clinical populations. In this study, the Miller Hope Scale was used to measure hope near admission and at discharge for 192 psychiatric and chemically dependent inpatients. Hope scores near admission were significantly lower than the established norms for the instrument. Psychiatric patients were significantly lower in hope than chemically dependent patients at both times. At discharge, both subject groups approached the norms for the instrument. This study adds to the construct validity of the Miller Hope Scale and supports its use in clinical populations. PMID- 1897923 TI - Effects of controlled hyperoxygenation and endotracheal suctioning on intracranial pressure in head-injured adults. PMID- 1897924 TI - Power assessment inventory: tool development. PMID- 1897925 TI - Research data management: piles into files--locked and secured. PMID- 1897926 TI - The politics of research. PMID- 1897927 TI - Effect of insulin on the altered production of proteoglycans in rib cartilage of experimentally diabetic rats. AB - Costal cartilage from experimentally diabetic rats, labeled in vivo or in vitro with [35S]sulfate, was shown to incorporate less label into proteoglycans than cartilage from nondiabetic rats. Analyses of guanidine HCl cartilage extracts by gel chromatography on Sepharose CL-2B showed two major peaks at Kav approximately 0.4 and 0.8 (peaks I and II, respectively). Cartilage extracts from the diabetic rats contained predominantly peak II proteoglycans, while 60 and 55%, respectively, of the total 35S-labeled proteoglycans extracted from control cartilage labeled in vivo and in vitro with [35S]sulfate were present in peak I. After insulin treatment of the diabetic rats, the relative amount of peak I 35S labeled proteoglycans synthesized in vivo was increased to 70%. The overall in vivo incorporation of [35S]sulfate into proteoglycans was also stimulated in diabetic rats treated with insulin to levels above those found for control rats. Thus, diabetes-induced changes in the biosynthesis of rat costal cartilage proteoglycans may be alleviated by normalization of the diabetic state by insulin treatment. However, addition of insulin (10(-5)-10(-9) M) to the culture medium did not affect the amount of 35S-labeled proteoglycans synthesized in vitro or the relative amounts of peak I proteoglycans produced by control or diabetic cartilage, suggesting that insulin does not have a direct effect on proteoglycan production. Moreover, no decrease in the amount of 35S-labeled proteoglycans produced was found when glucose at high concentrations was present in the culture medium. However, the presence of rat serum resulted in an increase in the amount of 35S-labeled proteoglycans produced by both control and diabetic cartilage, demonstrating that the cartilage explants were metabolically responsive to stimulatory factors. PMID- 1897928 TI - Molecular cloning of the thymus-specific parvalbumin known as avian thymic hormone: isolation of a full length cDNA and expression of the recombinant protein in Escherichia coli. AB - The complete coding sequence of the thymus-specific parvalbumin called avian thymic hormone (ATH) has been cloned into Escherichia coli. The translated amino acid sequence was found to be identical to the sequence of map turtle parvalbumin at 90 of 108 positions. Northern blot analysis of thymic RNA indicated a transcript length of approximately 1050 bp. However, the ATH cDNA probe failed to hybridize to poly(A)+ RNA from chicken leg muscle, a further indication that avian thymic hormone is distinct from the muscle-associated parvalbumin previously isolated from chicken. Southern analysis of chicken genomic DNA suggests the presence of a single copy of the ATH gene, and the absence of hybridization between an ATH cDNA fragment and genomic DNA from rat and rabbit is confirmatory evidence that ATH expression is restricted to avian species. One of the full length ATH cDNA clones harbored an insert that lacked all 5' noncoding sequences. This cDNA was inserted without further alteration into the prokaryotic expression vector, pKK223-3. The resulting construction, which contains eleven base pairs between the Shine-Dalgarno sequence and the initiation codon, affords reasonably high levels of expression in E. coli. In most respects, recombinant ATH mimics the tissue-derived protein, retaining a similarly high affinity for Ca2+ ion (KCa = 14 +/- 5 nM). However, in contrast to ATH isolated from chicken thymus tissue, the N-terminal alanine of recombinant ATH is unacetylated. As a result, the isoelectric point is shifted upward from 4.3 to approximately 4.8. PMID- 1897929 TI - Isolation of a full-length cDNA encoding mouse aromatase P450. AB - A full-length cDNA clone for aromatase P450 has been isolated from a pregnant mouse ovarian cDNA library. The insert of this clone (2394 bp) contains a 1509-bp open reading frame encoding 503 amino acid residues together with a 46-bp 5' untranslated stretch and an 839-bp 3'-untranslated region to which a poly(A) tract is attached. Northern blot analysis of ovarian RNA from pregnant mice reveals a major mRNA band of 2.5 kb with a minor band of 2.1 kb. Comparison of mouse aromatase P450 with that of rat, human, and chicken shows 91, 81, and 69% identity in the nucleotide sequence and 92, 79, and 69% identity in the deduced amino acid sequence, respectively. The membrane-spanning domain of mouse aromatase P450 is estimated to be an extremely hydrophobic segment located within the N-terminal region of the molecule. Furthermore, a highly conserved heme binding domain is noticed. PMID- 1897930 TI - Elevated cholesterol and decreased sterol carrier protein-2 in peroxisomes from AS-30D hepatoma compared to normal rat liver. AB - Peroxisomes were isolated from AS-30D hepatoma and compared to normal rat liver cells for the purpose of investigating the cholesterol accumulation in the hepatoma cells. Cholesterol was found to be approximately 10-fold higher relative to protein in AS-30D peroxisomes as compared to peroxisomes from normal liver. The peroxisomes from the hepatoma cells were found to be more stable; catalase was not released from these peroxisomes during isolation or osmotic shock of the peroxisomal fraction. The elevated cholesterol level may stabilize the peroxisomal membrane. Sterol carrier protein-2 (SCP-2) levels were measured using a radioimmunoassay (RIA), which indicated the highest concentration of SCP-2 to be in peroxisomes. Hepatoma peroxisomes had a lower concentration of SCP-2 (2.5 micrograms/mg) than normal liver peroxisomes (8 micrograms/mg). Approximately half of all SCP-2 detected was found to be soluble in both hepatoma and normal rat liver cells. Immunoblots from both rat liver and AS-30D fractions demonstrated the presence of the 14-kDa form of SCP-2. The liver fractions also had a 57-kDa immunoreactive protein, which was barely detectable in the AS-30D fractions. The low abundance of the high molecular weight form of SCP-2 from hepatoma peroxisomes and the lower amounts of SCP-2 detected in the AS-30D peroxisomes may be related to the accumulation of cholesterol in the cells. PMID- 1897931 TI - A comparison of phospholipid degradation by oxidation and hydrolysis during the mitochondrial permeability transition. AB - The peroxidation and hydrolysis of mitochondrial phospholipids has been examined under conditions which are referable to induction of the permeability transition by t-butylhydroperoxide. Over a 30-min time course, the peroxide causes formation of 0.3 nmol/mg protein of malondialdehyde. This value is little effected by Ca2+, Sr2+, or Mn2+ but is increased approximately fivefold by Fe2+. The latter cation, but not the others, results in malondialdehyde formation in the absence of added peroxide. Partially oxidized phosphatidylethanolamine is present in normal mitochondria and is increased by approximately 50% following t-butylhydroperoxide treatment; however, the amounts observed are in the range of 0.4-0.6 mol% of total phosphatidylethanolamine. The minor degradation by peroxidation is in contrast to approximately 2.5 mol% degradation which occurs by hydrolysis. This degree of hydrolysis is accompanied by mitochondrial swelling and Mg2+ release, while a comparable level of peroxidation (malondialdehyde formation) is not. It is concluded that induction of the permeability transition by t butylhydroperoxide does not represent damage to the membrane lipid phase caused by peroxidation. It is possible, however, that peroxidation accelerates the accumulation of phospholipid hydrolysis products and is thereby a factor which favors the transition. PMID- 1897932 TI - Rapid purification and characterization of homoserine dehydrogenase from Saccharomyces cerevisiae. AB - Homoserine dehydrogenase of Saccharomyces cerevisiae has been rapidly purified to homogeneity by heat and acid treatments, ammonium sulfate fractionation, and chromatography on Matrex Gel Red A and Q-Sepharose columns. The final preparation migrated as a single entity upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis with a Mr of 40,000. The Mr of the native enzyme was 81,000 as determined by gel filtration, suggesting that the enzyme is composed of two identical subunits. This feature was also confirmed by cross-linking analysis using the bifunctional reagent dimethyl suberimidate. Feedback inhibition by L methionine and L-threonine was observed using the purified enzyme. The enzyme was markedly stabilized against heat treatment at high salt concentrations. Additions of feedback inhibitors or high concentrations of salts failed to cause any dissociation or aggregation of the enzyme subunits unlike enzymes from other sources such as Rhodospirillum rubrum. The enzyme denatured in 3 M guanidine-HCl was refolded by simple dilution with a concomitant restoration of the activity. Cross-linking analysis of the renaturation process suggested that the formation of the dimer is required for activity expression. Amino acid sequence analysis of peptides obtained by digestion of the enzyme protein with Achromobacter lyticus protease I revealed that several amino acid residues are strictly conserved among homoserine dehydrogenases from S. cerevisiae, Escherichia coli, and Bacillus subtilis. PMID- 1897933 TI - Assembly of the sea urchin extraembryonic hyaline layer; Ca2+ and Mg2+ act independently and at different sites on the pathway leading to hyalin-gel formation. AB - We have studied the interactions of Ca2+ with the sea urchin extraembryonic coat protein hyalin. As reported previously, Ca2+ alone was ineffective in inducing hyalin-gel (large aggregate) formation. This reaction required the additional presence of Mg2+ and NaCl. However, the results of tryptic digestion and nondenaturing agarose gel electrophoresis experiments demonstrated that Ca2+ could induce hyalin self-association into small aggregates in the absence of Mg2+ and NaCl. Magnesium did not modulate the interactions of Ca2+ with hyalin. In addition, Mg2+ had minimal effects on the conformation of hyalin. These results have been incorporated into a model delineating the pathway leading to hyalin-gel formation. PMID- 1897934 TI - Biochemical characteristics of a preneoplastic marker enzyme glutathione S transferase P-form(7-7). AB - Investigation of biochemical characteristics of the glutathione S-transferase P form (GST 7-7), a specific marker enzyme for preneoplastic cells arising during chemical hepatocarcinogenesis in the rat, revealed distinct functional differential from six other major GST forms. While the GST 7-7 substrate specificity was generally broader, binding ability for diverse organic anions such as bilirubin, hematin, and sulfobromophthalein was as high as in any of the other six forms. Furthermore, the enzymatic activity of GST 7-7 was found to be highly insensitive to the inhibitory actions of a wide range of organic anions at physiological pH in contrast to the other forms which proved more susceptible. The functional characteristics of GST 7-7 may in part account for its overproduction in the preneoplastic cells. PMID- 1897935 TI - Cytochrome b5-mediated redox cycling of estrogen. AB - Previously, we have demonstrated microsomal cytochrome P450-catalyzed redox cycling of estrogens. In this study, we investigated the role of cytochrome b5 in redox cycling in order to obtain a full understanding of enzymatic contributions to redox reactions of estrogens. Pure cytochrome P450c and hydrogen peroxide or cumene hydroperoxide oxidized diethylstilbestrol (DES) to diethylstilbestrol 4',4"-quinone (DES Q). This oxidation by H2O2 was doubled by addition of cytochrome b5 to cytochrome P450c (molar ratio of 1:4), but did not proceed with cytochrome b5 alone. The stimulation by cytochrome b5 of the cytochrome P450c catalyzed oxidation of DES to DES Q occurred via modulation of the Vmax of cytochrome P450c rather than of the Km. DES Q was reduced to DES by purified cytochrome b5 and NADH-dependent cytochrome b5 reductase. Pretreatment of microsomes with an antibody to cytochrome b5 reductase inhibited microsomal NADH dependent reduction of DES Q to DES by 55%. Cytochrome b5 likely participates in the oxidation of DES to DES Q by interacting with cytochrome P450c and in the reduction of DES Q to DES by interacting with cytochrome b5 reductase. Thus, the study demonstrates that cytochrome b5 plays an active role in biological oxidation and reduction reactions. PMID- 1897936 TI - Interactions of iodide ions with isolated photosystem 2 particles. AB - The effects of I- ions on O2 evolution by photosystem 2 particles, which were depleted of the 18-kDa and the 23-kDa extrinsic proteins of the O2 evolution complex by NaCl washing (dPS2 particles) were examined. In the absence of Cl- (incompetent dPS2) I- stimulated O2 evolution up to 3-6 mM, depending on the associated cation, and inhibited it at higher concentrations. In the presence of Cl- (competent dPS2), I- was inhibitory at all concentrations. The inhibition was reversible, it occurred at a site preceding Tyrz (Tyr residue mediating electron transfer from H2O to photosystem 2), and it interfered noncompetitively with the reactivation of incompetent dPS2 with Cl-. Furthermore, the organic salts tetrabutyl ammonium iodide and tetraphenyl phosphonium iodide proved to be stronger inhibitors than the inorganic NaI. This is interpreted as an indication of a negatively charged surface, situated behind a hydrophobic permeability barrier. Permeant organic cations, being better compensators of the inner surface charge than Na+, are also more apt in facilitating access of the I- ions to the inhibitory site in the vicinity of Tyrz. PMID- 1897937 TI - The effect of alpha-tocopherol as an antioxidant on the oxidation of membrane protein thiols induced by free radicals generated in different sites. AB - Azo compounds enable us to generate peroxyl radicals by thermal decomposition at a constant rate and at a desired site, that is, water-soluble compounds produce initiating radicals in an aqueous phase and lipid-soluble compounds initiate the oxidation within the membrane-lipid layer. Using these radicals generated in different sites, we oxidized red blood cell ghost membranes to study the relationships between alpha-tocopherol depletion, initiation of lipid peroxidation, and protein damage. When radicals were generated in the aqueous phase, the loss of membrane protein thiols was observed concurrently with the consumption of membrane tocopherol and after tocopherol was exhausted the peroxidation of membrane lipids occurred. On the other hand, when radicals were initiated within the lipid region, the oxidation of thiols and the formation of thiobarbituric acid-reactive substances were suppressed to give an induction period until tocopherol fell below a critical level. Our results indicate that the surface thiols of extrinsic proteins may compete with alpha-tocopherol for trapping aqueous radicals and spare tocopherol to some extent, whereas the oxidation of intrinsic buried thiols may commence due to lipid-derived radicals produced after tocopherol was consumed. In conclusion, alpha-tocopherol in the membrane can break the free radical chain efficiently to inhibit the lipid peroxidation. However, the effect of tocopherol on the inhibition of membrane protein damage, exhibited by the loss of thiols and the formation of high molecular-weight proteins, would be different depending on the site of initial radical generation. PMID- 1897939 TI - Spectral resolution of long term (0.5-50 s) delayed fluorescence from spinach chloroplasts. AB - The emission spectrum of room temperature delayed fluorescence from spinach chloroplasts does not change during the period 0.5-50 s after the cessation of illumination. This provides experimental evidence that charge recombination processes originating in various charge pairs of photosystem II, and manifest as various kinetical components of long term delayed fluorescence, result in the excitation of the same emitters, as predicted by the charge recombination hypothesis. PMID- 1897938 TI - Complete amino acid sequence of the type III isozyme of rat hexokinase, deduced from the cloned cDNA. AB - Clones containing cDNA coding for the Type III isozyme of rat hexokinase (ATP:D hexose 6-phosphotransferase, EC 2.7.1.1) were isolated from a library prepared in lambda gt10 with rat liver mRNA. Three clones were characterized. Their composite sequence includes the entire coding region for Type III hexokinase, 3' untranslated sequence extending into the polyadenylated region, and 80 bp of 5' untranslated sequence. Extensive similarity in sequence of N- and C-terminal halves of the enzyme, previously seen with the Type I isozyme, is consistent with the view that these 100-kDa mammalian hexokinases are the evolutionary result of duplication and fusion of a gene coding for an ancestral hexokinase having a molecular weight of approximately 50 kDa. Extensive similarities are seen between sequences of the Type I and III isozymes, and those reported for mammalian glucokinase (also called Type IV hexokinase) and for the hexokinase and glucokinase of yeast. Residues thought to be involved in catalytic function are highly conserved in all of these enzymes. Based on a quantitative comparison of sequence similarities, it is concluded that the 50-kDa mammalian glucokinase is more closely related to the 100-kDa mammalian enzymes than it is to the 50-kDa enzymes from yeast. One interpretation of this might be that the mammalian glucokinase arose by resplitting of the gene coding for the 100-kDa mammalian hexokinases. PMID- 1897940 TI - The effect of the 3'-OH group on the conformation and binding ability of anhydropyrimidine nucleosides to uridine phosphorylase. AB - 2,2'-Anhydro-3'-deoxy-5-ethyluridine, a new pyrimidine nucleoside analog, has been examined in terms of its binding potency to uridine phosphorylase, and its conformation in solution (NMR) was studied. 2,2'-Anhydro-3'-deoxy-5-ethyluridine has a Ki value of 3.4 microM for uridine phosphorylase from rat intestinal mucosa. This value is approximately one order of magnitude lower than the Km for uridine (22 microM), the natural substrate. The presence of the 3'-OH group (in the ribo-configuration) on pyrimidine nucleoside analogs may not be considered a prerequisite for the binding to uridine phosphorylase; however, it enhances the binding in the case of flexible ligands cooperating in the process of conformation change toward a more favorable enzyme-ligand interaction. The presence of the 3'-OH group in pyrimidine nucleosides seems to be essential if the molecule is to become a substrate. PMID- 1897941 TI - Reaction of xanthine oxidase-derived oxidants with lipid and protein of human plasma. AB - Xanthine oxidase and purines have recently been detected in the circulation during acute viral infection and following hepatotoxicity and shock. Reactions of xanthine oxidase-generated oxidants with human plasma or bovine serum albumin (BSA) and egg phosphatidylcholine (PC) liposomes have been studied by measuring protein sulfhydryl oxidation and two markers of free radical-mediated lipid peroxidation, thiobarbituric acid reactive substances (TBARS) and conjugated dienes. Plasma incubated with 5 mU/ml xanthine oxidase (XO) and 0.5 mM hypoxanthine (Hx) for 2 h at 37 degrees C had 25-53% oxidation of sulfhydryl groups, with greater than 80% of the oxidation occurring during the first 20 min of the reaction. Concentrations of BSA similar to those present in serum, when exposed to XO/Hx-mediated oxidative stress, showed an even greater decrease in sulfhydryl concentration than that of plasma. No significant increase in plasma TBARS and conjugated dienes was observed during the 2-h incubation period in the presence of XO. Egg PC liposomes, suspended to a plasma phospholipid-equivalent concentration, showed a minor increase in TBARS and conjugated dienes under similar XO/Hx incubation conditions. In the presence of 0.23 mM BSA, lipid peroxidation was completely inhibited. A similar inhibition of lipid peroxidation was induced by cysteine but not by uric acid. Electrophoretic and arsenite mediated sulfur reduction analysis revealed that BSA was oxidized beyond the disulfide form, with sulfenic acid formed during the initial period of oxidation. Protein sulfhydryls served as sacrificial antioxidants, preventing plasma lipid peroxidation, as well as being targets for oxidative damage. Plasma protein thiol oxidation was determined to be a more sensitive and specific indication of oxidant stress to the vascular compartment than assessment of lipid oxidation byproducts. PMID- 1897942 TI - Studies on yeast peroxisomal citrate synthase. AB - Peroxisomal (nonmitochondrial) citrate synthase (CS2) has been purified from a Saccharomyces cerevisiae strain in which the gene for the mitochondrial citrate synthase (CS1) had been disrupted and no CS1 protein is produced. The enzyme, CS2, the sequence of which had been previously determined from its DNA, behaved differently from CS1 in its purification, kinetics, stability, and binding to the inner surface of mitochondrial inner membranes. PMID- 1897943 TI - Inhibition of mitochondrial respiration by neutral, monocationic, and dicationic bis-pyridines related to the dopaminergic neurotoxin 1-methyl-4-phenylpyridinium cation (MPP+). AB - The cytotoxic effect of the dopaminergic neurotoxin 1-methyl-4-phenylpyridinium (MPP+) is believed to be associated with a compromise in cellular energy arising as a consequence of its persistent inhibition of mitochondrial respiration. MPP+ is a rather weak inhibitor of electron transport, but it undergoes passive accumulation inside actively respiring mitochondria in response to the transmembrane electrochemical potential gradient. In order to test the prediction that dicationic analogs of MPP+ might be concentrated to a much greater extent and thereby exert especially potent inhibition of respiration on the intact organelle, we synthesized four differently spaced bis-pyridines, each in neutral, monocationic, and dicationic forms, and evaluated their inhibitory activities in intact mitochondria and in electron transport particles (ETP). Compared to the neutrals, the monocations and especially the dications exhibit reduced inhibition in ETP, but the inhibition in mitochondria is enhanced selectively for the cationic inhibitors presumably on account of their accumulation in the mitochondrial matrix. This enhancement is limited by the relatively poor ability of the cationic bis-pyridines to enter mitochondria, as judged from experiments which evaluated the rate of onset of inhibition (without preincubation), in the absence and presence of tetraphenylborate (TPB-). The dications appear to be transported less well than the monocations, and only the most lipophilic dication exhibited a substantially greater accumulation-dependent enhancement of inhibitory activity on mitochondria than did the corresponding monocation. The compounds studied here constitute a novel class of respiratory chain probes which may be useful for a variety of studies on mitochondria. PMID- 1897944 TI - Modulation of class Pi glutathione transferase activity by sulfhydryl group modification. AB - Glutathione transferases (GSTs) in Class Pi (rat GST-P (7-7) and human GST-pi) were inactivated by treatment with 0.05-1 mM hydrogen peroxide (H2O2), while GSTs in Class Alpha (1-2) and Class Mu (3-3, 3-4) were not, even with 5 mM H2O2. In the presence of 1 mM reduced glutathione (GSH), the inactivated GST-P (-pi) was effectively reactivated by the action of thioltransferase, which had been partially purified from rat liver by GSH-Sepharose affinity chromatography and gel filtration using Sephadex G-75. Thus, inactivation of GST-P by H2O2 was indicated to involve concomitant formation of disulfide bonds between cysteinyl residues. Single GST-P or GST-pi subunits are known to have four cysteinyl residues at the same positions, which can react with sulfhydryl group modifiers. On sodium dodecyl sulfate-polyacrylamide gel electrophoresis, GST-P treated with 1 mM H2O2 showed several extra bands, at least three, with apparent molecular weights of 21.5, 18, 37 kDa in addition to the native GST-P subunit band with a molecular weight of 23.5 kDa. These extra bands were identified as inactive forms since they returned to the native band with accompanying restoration of the activity when treated with dithiothreitol, mercaptoethanol, or thioltransferase. Disulfide bonds were formed mainly within subunits, causing an apparent reduction in molecular weight, only small amounts of binding between subunits being observed. PMID- 1897945 TI - Hexokinase of rat brain mitochondria: relative importance of adenylate kinase and oxidative phosphorylation as sources of substrate ATP, and interaction with intramitochondrial compartments of ATP and ADP. AB - Interactions between intramitochondrial ATP-generating, ADP-requiring processes and ATP-requiring, ADP-generating phosphorylation of glucose by mitochondrially bound hexokinase (ATP:D-hexose 6-phosphotransferase, EC 2.7.1.1) have been investigated using well-coupled mitochondria isolated from rat brain. ADP generated by mitochondrially bound hexokinase was more effective at stimulating respiration than was ADP generated by hexokinase dissociated from the mitochondria, and pyruvate kinase was less effective as a scavenger of ADP generated by the mitochondrially bound hexokinase than was the case with ADP generated by the dissociated enzyme. These results indicate that ADP generated by the mitochondrially bound enzyme is at least partially sequestered and directed toward the mitochondrial oxidative phosphorylation apparatus. Under the conditions of these experiments, the maximum rate of ATP production by oxidative phosphorylation was approximately 10-fold greater than the maximum rate of ATP generation by the adenylate kinase reaction. Moreover, during periods of active oxidative phosphorylation, adenylate kinase made no detectable contribution to ATP production. Thus, adenylate kinase does not represent a major source of ATP for hexokinase bound to actively phosphorylating brain mitochondria. With adenylate kinase as the sole source of ATP, a steady state was attained in which ATP formation was balanced by utilization in the hexokinase reaction. In contrast, when oxidative phosphorylation was the source of ATP, a steady state rate of Glc phosphorylation was attained, but it was equivalent to only about 40 50% of the rate of ATP production and thus there was a continued net increase in ATP concentration in the system. Rates of Glc phosphorylation with ATP generated by oxidative phosphorylation exceeded those seen with equivalent levels of exogenously added ATP. Moreover, at total ATP concentrations greater than approximately 0.2 mM, hexokinase bound to actively phosphorylating mitochondria was unresponsive to continued slow increases in ATP levels; acute increase in ATP (by addition of exogenous nucleotide) did, however, result in increased hexokinase activity. The relative insensitivity of mitochondrially bound hexokinase to extramitochondrial ATP suggested dependence on an intramitochondrial pool (or pools) of ATP during active oxidative phosphorylation. Two intramitochondrial compartments of ATP were identified based on their selective release by inhibitors of electron transport or oxidative phosphorylation. These compartments were distinguished by their sensitivity to inhibitors and the kinetics with which they were filled with ATP generated by oxidative phosphorylation. Exogenous glycerol kinase competed effectively with mitochondrially bound hexokinase for extramitochondrial ATP, with relatively low levels of glycerol kinase completely inhibiting phosphorylation of Glc.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1897946 TI - Ustilago maydis virus P4 killer toxin: characterization, partial amino terminus sequence, and evidence for glycosylation. AB - The toxin from Ustilago maydis virus P4 was purified to homogeneity and characterized. The native molecular mass, using size-exclusion HPLC was estimated to be 7.2 kDa. The purified toxin was composed of a single subunit. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis under reduced and nonreduced conditions resulted in estimated molecular masses of 8.4 and 7.4 kDa, respectively. The purified toxin was found to be glycosylated when tested for carbohydrates using the phenol-sulfuric acid method, Schiff's base reagent, and a Glycan detection kit and when probed against different biotinylated lectins. Partial amino acid sequence analysis of the purified toxin indicated a free N terminus, 16% glycine, and 23% basic amino acid residues. No homology was found to either the alpha or the beta subunit of the toxin encoded by U. maydis infected with the P6 virus. PMID- 1897947 TI - Effects of compression on the loss of newly synthesized proteoglycans and proteins from cartilage explants. AB - The effects of mechanical compression of calf cartilage explants on the catabolism and loss into the medium of proteoglycans and proteins radiolabeled with [35S]sulfate and [3H]proline were examined. A single 2- or 12-h compression of 3-mm diameter cartilage disks from a thickness of 1.25 to 0.50 mm, or slow cyclic compression (2 h on/2 h off) from 1.25 mm to 1.00, 0.75, or 0.50 mm for 24 h led to transient alterations and/or sustained increases in loss of radiolabeled macromolecules. The effects of imposing or removing loads were consistent with several compression-induced physical mediators including fluid flow, diffusion, and matrix disruption. Cyclic compression induced convective fluid flow and enhanced the loss of 35S- and 3H-labeled macromolecules from tissue into medium. In contrast, prolonged static compression induced matrix consolidation and appeared to hinder the diffusional transport and loss of 35S- and 3H-labeled macromolecules. Since high amplitude cyclic compression led to a sustained increase in the rate of loss of 3H- and 35S-labeled macromolecules that was accompanied by an increase in the rate of loss of [3H]hydroxyproline residues and an increase in tissue hydration, such compression may have caused disruption of the collagen meshwork. The 35S-labeled proteoglycans lost during such cyclic compression were of smaller average size than those from controls, but contained a similarly low proportion (approximately 15%) that could form aggregates with excess hyaluronate and link protein. The size distribution and aggregability of the remaining tissue proteoglycans and 35S-labeled proteoglycans were not markedly affected. The loss of tissue proteoglycan paralleled the loss of 35S labeled macromolecules. This study provides a framework for elucidating the biophysical mechanisms involved in the redistribution, catabolism, and loss of macromolecules during cartilage compression. PMID- 1897948 TI - Stabilization of the Escherichia coli elongation factor Tu-GTP-aminoacyl-tRNA complex. AB - The effect of ammonium sulfate on the Escherichia coli elongation factor Tu-GTP aminoacyl-tRNA complex has been studied. The half-lives of 12 E. coli aminoacyl tRNA species were determined at 37 degrees C in the presence and absence of an equimolar amount of EF-Tu-GTP and in the presence and absence of 1.5 M ammonium sulfate. The results indicate that the addition of 1.5 M ammonium sulfate to the ternary complex increased the stability of all 12 complexes studied. In addition, the effects of various salts and crystallization agents on the stability of the E. coli EF-Tu-GTP-phenylalanyl-tRNA complex was studied in detail. Binding parameters were also measured under various conditions at 37 degrees C. The results indicate that the stability and the Kassoc of the ternary complex, using phenylalanyl-tRNA, can be increased by the presence of polyethylene glycol or ammonium sulfate. PMID- 1897950 TI - Purification, characterization, and subcellular localization of an acid phosphatase from black mustard cell-suspension cultures: comparison with phosphoenolpyruvate phosphatase. AB - An acid phosphatase from Brassica nigra (black mustard) leaf petiole cell suspension cultures has been purified 1633-fold to a final specific activity of 1225 (mumols orthophosphate produced/min)/mg protein and near homogeneity. The native protein was a glycosylated monomer having a molecular mass of 60 kDa and a pI of 4.5. The enzyme displayed a broad pH optimum of about pH 5.6 and was heat stable. The final preparation hydrolyzed a wide variety of phosphate esters. The highest specificity constants were obtained with 3-phosphoglycerate, 2,3 diphosphoglycerate, PPi, and phosphoenolpyruvate (PEP). The enzyme was activated 1.4-fold by 4 mM Mg2+ or Mn2+, but was strongly inhibited by Mo, Pi, F, and several phosphorylated compounds. Subcellular localization experiments revealed that this nonspecific acid phosphatase is probably a secreted enzyme, localized in the cell wall. By contrast, B. nigra PEP phosphatase appeared to be localized in the cell vacuole. Peptide mapping via CNBr fragmentation was employed to investigate the structural relatedness of the two phosphatases. Their respective CNBr cleavage patterns were dissimilar, suggesting that B. nigra acid and PEP phosphatases are distinct polypeptides. Putative metabolic functions of these two phosphatases are discussed in relation to the biochemical adaptations of B. nigra cell-suspension cultures to nutritional phosphate deprivation. PMID- 1897949 TI - Transitory DNA hypomethylation during liver cell proliferation induced by a single dose of lead nitrate. AB - In the present study we have examined the effect of a single dose of the mitogen lead nitrate (75 mumols/kg body wt) on the methylation status of hepatic DNA in male Wistar rats. It was found that extensive hypomethylation of hepatic DNA occurs in mitogen-treated rat liver. This effect could be seen as early as 12 h after metal treatment and parallels the changes in liver weight. Probing with the methylation-sensitive enzymes HpaII, MspI, and HaeIII confirmed HPLC analyses and showed that methylation at these sites was affected by lead treatment. DNA hypomethylation has already been found in regenerating rat liver and in hepatic (pre)malignant lesions when compared to normal nondividing liver. Thus the lowering of the DNA 5-methylcytosine content appears to be a property characteristic of cellular proliferation, regardless of whether it is caused by partial hepatectomy, carcinogen treatments, or mitogen administration. PMID- 1897952 TI - Mechanisms of 1,3-butadiene oxidations to butadiene monoxide and crotonaldehyde by mouse liver microsomes and chloroperoxidase. AB - NADPH-dependent oxidation of 1,3-butadiene by mouse liver microsomes or H2O2 dependent oxidation by chloroperoxidase produced both butadiene monoxide and crotonaldehyde; methyl vinyl ketone and 2,3- and 2,5- dihydrofuran were not detected. The crotonaldehyde to butadiene monoxide ratio remained constant over time in both the microsomal and the chloroperoxidase reactions; however, much more crotonaldehyde was produced by chloroperoxidase than microsomes; crotonaldehyde was not detected when reference samples of butadiene monoxide were used in control incubations containing NADPH and microsomes or H2O2 and chloroperoxidase. Moreover, incubations of 1,3-butadiene with horseradish peroxidase and H2O2, or microsomes and H2O2 or arachidonic acid did not result in the oxidation of 1,3-butadiene. In microsomes, metabolite formation was dependent on incubation time, NADPH, and protein concentrations and did not change when the 1,3-butadiene pressure was varied between 24 and 52 cm Hg. Inclusion of the cytochrome P450 inhibitor 1-benzylimidazole inhibited 1,3-butadiene metabolism, but inclusion of KCN, catalase, or superoxide dismutase had no effect. These results support the role of cytochrome P450 in 1,3-butadiene oxidation by mouse liver microsomes. The formation of crotonaldehyde but not methyl vinyl ketone by cytochrome P450 or chloroperoxidase indicates regioselectivity in the oxygen transfer from the hemoproteins to 1,3-butadiene. The intermediates formed may undergo either ring closure to form butadiene monoxide or a hydrogen shift to form 3-butenal which tautomerizes to produce crotonaldehyde. Evidence for this tautomerization was obtained by the finding that 3-buten-1-ol, an alternative precursor of 3-butenal, was oxidized to crotonaldehyde under incubation conditions similar to that used for 1,3-butadiene. PMID- 1897951 TI - Luminol peroxidation catalyzed by human isoferritins. AB - The role of ferritin in catalyzing the oxidation of luminol with the production of chemiluminescence was investigated. The effect of pH was compared to its effect on K3Fe(CN)6-catalyzed oxidation and different pH optima were recorded for the two catalysts. The ferrous iron chelator, bipyridyl, enhanced the production of chemiluminescence catalyzed by FeSO4 and ferritin but had little effect on the K3Fe(CN)6-catalyzed reaction. Desferal reduced the level of chemiluminescence in the presence of FeSO4 and ferritin but was a much more effective inhibitor of chemiluminescence catalyzed by K3Fe(CN)6. The hydroxyl radical scavenger, mannitol, had little effect upon light production whereas superoxide dismutase inhibited light production. The addition of antihuman spleen ferritin completely inhibited activity. The catalytic activity of both H and L rich ferritins was affected by iron content. Activity increased until the Fe/protein ratio reached 0.04 micrograms Fe/micrograms protein and then decreased with increasing iron content. Thus activity is controlled by the iron content of the molecule and influenced by its subunit composition as is the uptake of iron into ferritin. These findings suggest that ferroxidation by ferritin is associated with the ability to generate radicals of the nitrogenous base luminol with the production of chemiluminescence. Although activity is greatest at alkaline pH there is significant activity at pH 7.4. Ferritin therefore may be able to generate free radical reactions in vivo with the acidic isoferritin being most active. PMID- 1897953 TI - Reconstitution of the Deinococcus radiodurans aposuperoxide dismutase. AB - Deinococcus radiodurans, a radiation-resistant aerobe, synthesized a 43,000 Mr dimeric superoxide dismutase. The holoenzyme, sp act 3300 U/mg, contained 1.5 g atoms Mn, 0.6 g-atom Fe, and 0.1 g-atom Zn per mole dimer. Apoprotein, prepared by dialysis of the holoenzyme in denaturant plus chelator and then renatured in chelex-treated Tris chloride buffer, rapidly regained superoxide dismuting activity upon incubation in 1 mM MnCl2. Reconstitution was dependent on Mn concentration and pH. The Mn-reconstituted protein, sp act 3560 U/mg, contained 1.7 g-atoms Mn per mole dimer. The holoenzyme and Mn-reconstituted apoprotein migrated with the same patterns in 10% acrylamide gels and focused to the same pattern upon isoelectric focusing. Fluorescence emission maxima of the holoenzyme, Mn-reconstituted apoprotein, and the renaturated apoprotein were 329 +/- 1 nm but differed from the denatured apoprotein (352 nm). Apoprotein bound 1.7 g-atoms Zn and from 3-7 g-atoms Fe per mole dimer on incubation with 1 mM ZnSO4 and Fe(NH4)2(SO4)2, respectively. Although neither Zn nor Fe restored superoxide dismuting activity, the ferrous and the zinc salt inhibited reconstitution of the apoprotein with manganese. Metal addition to renatured aposuperoxide dismutase offers a novel approach to reconstitution of procaryote superoxide dismutases. PMID- 1897954 TI - Alpha-tocopherol (vitamin E) regulates vascular smooth muscle cell proliferation and protein kinase C activity. AB - Alpha-Tocopherol (vitamin E) protects against free radical damage, which has been implicated in aging, cancer initiation, and atherosclerosis. We have found that physiological concentrations of alpha-tocopherol specifically inhibited aorta smooth muscle cell (VSMC, line A7r5) proliferation and protein kinase C (PKC) activity. Other water and lipid soluble antioxidants were inactive. alpha Tocopherol inhibition of PKC and of VSMC proliferation may represent a physiological mechanism, relevant to the onset of diseased states such as atherosclerosis. PMID- 1897955 TI - PMN elastases: a comparison of the specificity of human isozymes and the enzyme from other species toward substrates and inhibitors. AB - The human elastases isolated from polymorphonuclear neutrophils (PMN) and purulent sputum displayed identical kinetic constants toward substrates and inhibitors. The elastases from the two sources yield identical N-terminal sequences and were recognized by antiserum prepared against human sputum elastase (HSE) isozyme-4 (I-4). The data support the proposal put forth by Twumasi and Liener (1977, J. Biol. Chem. 252, 1917-1926) that the human elastase from sputum is of PMN origin. PMN elastases from other species displayed kinetic constants toward both substrates and inhibitors significantly different from the human enzyme. Therefore, extrapolation of inhibitor profiles from these elastases to the human source should be avoided. Four groups of isozymes were resolved from HSE by FPLC. Only the most basic isozyme (I-4) was obtained as a single species. The isozymes displayed identical macroscopic kinetic constants toward several substrates and two classes of inhibitors. The similar partition ratios observed with a cephalosporin-derived inhibitor suggest that the microscopic rate constants are also identical. The data support the proposal suggested by Baugh and Travis (1976, Biochemistry 15, 836-841) that HLE isozymes differ only in carbohydrate content. Whatever the source of human PMN elastase heterogeneity, it does not result in heterogeneous catalytic properties. In addition, a new protein was identified in elastase preparations derived from human sputum. This protein displayed homology to serine proteases and properties suggesting that it is identical to azurocidin. PMID- 1897956 TI - Interaction of fatty acids with recombinant rat intestinal and liver fatty acid binding proteins. AB - Intestinal enterocytes contain two homologous fatty acid-binding proteins, intestinal fatty acid-binding protein (I-FABP)2 and liver fatty acid-binding protein (L-FABP). Since the functional basis for this multiplicity is not known, the fatty acid-binding specificity of recombinant forms of both rat I-FABP and rat L-FABP was examined. A systematic comparative analysis of the 18 carbon chain length fatty acid binding parameters, using both radiolabeled (stearic, oleic, and linoleic) and fluorescent (trans-parinaric and cis-parinaric) fatty acids, was undertaken. Results obtained with a classical Lipidex-1000 binding assay, which requires separation of bound from free fatty acid, were confirmed with a fluorescent fatty acid-binding assay not requiring separation of bound and unbound ligand. Depending on the nature of the fatty acid ligand, I-FABP bound fatty acid had dissociation constants between 0.2 and 3.1 microM and a consistent 1:1 molar ratio. The dissociation constants for L-FABP bound fatty acids ranged between 0.9 and 2.6 microM and the protein bound up to 2 mol fatty acid per mole of protein. Both fatty acid-binding proteins exhibited relatively higher affinity for unsaturated fatty acids as compared to saturated fatty acids of the same chain length. cis-Parinaric acid or trans-parinaric acid (each containing four double bonds) bound to L-FABP and I-FABP were displaced in a competitive manner by non-fluorescent fatty acid. Hill plots of the binding of cis- and trans- parinaric acid to L-FABP showed that the binding affinities of the two sites were very similar and did not exhibit cooperativity. The lack of fluorescence self quenching upon binding 2 mol of either trans- or cis-parinaric acid/mol L-FABP is consistent with the presence of two binding sites with dissimilar orientation in the L-FABP. Thus, the difference in binding capacity between I-FABP and L-FABP predicts a structurally different binding site or sites. PMID- 1897957 TI - The ionization states of the 5'-phosphate group in the various coenzyme forms bound to mitochondrial aspartate aminotransferase. AB - We have carried out a Fourier transform infrared spectroscopic study of mitochondrial aspartate aminotransferase in the spectral region where phosphate monoesters give rise to absorption. Infrared spectra in the above-mentioned region are dominated by protein absorption. Yet, below 1020 cm-1 protein interferences are minor, permitting the detection of the band arising from the symmetric stretching of dianionic phosphate monoesters [T. Shimanouchi, M. Tsuboi, and Y. Kyogoku (1964) Adv. Chem. Phys. 8, 435-498]. The integrated intensity of this band in several enzyme forms (pyridoxal phosphate, pyridoxamine phosphate, and sodium borohydride-reduced, pyridoxyl phosphate form) does not change with pH in the range 5-9. This behavior contrasts that of free pyridoxal phosphate (PLP) and pyridoxamine phosphate (PMP) in solution, where the dependence of the same infrared band intensity with pH can be correlated to the known pK values for the 5'-phosphate ester in solution. The integrated intensity value of this infrared band for the PLP enzyme form before and after reduction with sodium borohydride is close to that given by free PLP at pH 8-9. These results are taken as evidence that in the active site of mitochondrial aspartate aminotransferase the 5'-phosphate group of PLP remains mostly dianionic even at a pH near 5. Thus, it is suggested that the chemical shift changes associated with pH titrations of various PLP forms reported in a previous 31P NMR study of this enzyme [M. E. Mattingly, J. R. Mattingly, and M. Martinez-Carrion (1982) J. Biol. Chem. 257, 8872] are due to the fact that the phosphorus chemical shift senses the O-P-O bond distortions induced by the ionization of a nearby residue. Since no chemical shift changes were observed in pH titrations of the PMP forms (lacking an ionizable internal aldimine) of this isozyme, the Schiff base between PLP and Lys-258 at the active site is the most likely candidate for the ionizing group influencing the phosphorus chemical shift in this enzyme. PMID- 1897959 TI - Paraquat-resistant HeLa cells: increased cellular content of glutathione peroxidase. AB - Paraquat-resistant HeLa cells were selected and characterized to determine the mechanism(s) of the toxic action of paraquat for cultured mammalian cells. From HeLa cells already selected for resistance to the toxicity of 40 microM paraquat more resistant cells were selected in 90 microM paraquat. In these more resistant cells (PQRHM90) one adaptation which occurred at the lesser concentration of paraquat, magnification of the cellular content of both the CuZn- and the Mn containing superoxide dismutases, did not increase further. Instead, the cellular content of catalase and of glutathione peroxidase increased. The increased cellular content of glutathione peroxidase appeared more likely to have produced increased resistance to paraquat than did the augmented content of catalase because, after cultivation in the absence of paraquat, the cells retained both resistance to 90 microM paraquat and the increased content of glutathione peroxidase, while the content of catalase declined. The cellular content of reduced glutathione in the PQRHM90 cells grown in paraquat was diminished in comparison with that in the cells from which they derived. The data suggest that the PQRHM90 cells resisted the toxicity of paraquat by increasing the cellular activity of glutathione peroxidase as a means of detoxifying the H2O2 produced by paraquat. PMID- 1897958 TI - Cytotoxicity of alkylating agents in isolated rat kidney proximal tubular and distal tubular cells. AB - Patterns of chemical-induced cytotoxicity in different regions of the nephron were studied with freshly isolated proximal tubular and distal tubular cells from rat kidney. Three model alkylating agents, methyl vinyl ketone, allyl alcohol, and N-dimethylnitrosamine, were used as test chemicals. Methyl vinyl ketone and a metabolite of allyl alcohol, acrolein, are Michael acceptors that bind to cellular protein sulfhydryl groups and GSH. N-Dimethylnitrosamine binds to cellular protein and DNA. Lactate dehydrogenase leakage was used to assess irreversible cellular injury. Distal tubular cells were more susceptible than proximal tubular cells to injury produced by methyl vinyl ketone or allyl alcohol while the two cell populations were equally susceptible to injury produced by N dimethylnitrosamine. Preincubation of both proximal tubular and distal tubular cells with GSH protected them from methyl vinyl ketone- and allyl alcohol-induced cytotoxicity but had no effect on N-dimethylnitrosamine-induced cytotoxicity. Similarly, incubation of cells with methyl vinyl ketone or allyl alcohol, but not N-dimethylnitrosamine, altered cellular GSH status. As with GSH status, incubation of cells with methyl vinyl ketone or allyl alcohol, but not N dimethylnitrosamine, caused pronounced inhibitory effects on mitochondrial function, as evidenced by ATP depletion and inhibition of cellular oxygen consumption. These results demonstrate that alkylating agents are cytotoxic to both proximal tubular and distal tubular cells, and that interaction with cellular GSH is a factor determining nephron cell type specificity of injury. PMID- 1897960 TI - Characterization and partial amino acid sequence of human plasma glutathione peroxidase. AB - Human plasma glutathione peroxidase was purified to homogeneity and partially sequenced. Overlapping peptide fragments from three endopeptidase digests permitted the determination of one sequence of 32 contiguous amino acids and one sequence of 23 contiguous amino acids. Five additional unique peptide sequences without obvious overlaps were obtained. The sequence of 32 amino acid residues aligns with positions 82-113 of human cytosolic glutathione peroxidase with nine mismatches without gaps or insertions. The sequence of 23 amino acid residues aligns with positions 157-178 with six mismatches and an insertion of one residue. Three additional peptide sequences with no obvious sequence homology to glutathione peroxidase can be aligned based on the sequence of a cDNA clone encoding plasma glutathione peroxidase that was isolated from a human placental library. The plasma enzyme is a homotetramer composed of 21-kDa subunits which cannot reduce phospholipid hydroperoxides. These results indicate that the plasma glutathione peroxidase is distinct from both the classical cytosolic enzyme and the monomeric phospholipid hydroperoxide glutathione peroxidase. Only a negligible amount of glutathione peroxidase activity was detected in bile, indicating that the liver exports plasma glutathione peroxidase exclusively to the circulation. PMID- 1897961 TI - Post-translational modifications and binding properties of the apically secreted 80-kDa glycoprotein from Madin-Darby canine kidney cells: similarities to the C terminal portion of the basolaterally secreted fibronectin. AB - Apically secreted 80-kDa glycoprotein (gp 80) from Madin-Darby canine kidney cells was found to be immunoprecipitated by the polyclonal antiserum against fibronectin or a monoclonal antibody specific for the fibronectin C-terminal fibrin binding domain. Upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), gp 80 migrated as a doublet band under nonreducing conditions. Under reducing conditions, gp 80 was resolved into three distinct bands, respectively of 45-, 40-, and 35-kDa molecular mass. Analysis by two dimensional SDS-PAGE revealed that gp 80 exists in two molecular forms: one consisting of a 45-kDa subunit and a 40-kDa subunit, and one consisting of a 45 kDa subunit and a 35-kDa subunit. V-8 protease mapping indicated the 40 and 35 kDa subunits as being of the same homologous group and also as bearing partial homology to the 45-kDa subunit. Radioactive labeling revealed that labeled gp 80 was subjected to covalent modifications by sulfation and phosphorylation. Sulfate analysis showed that [35S]sulfate-labeled gp 80 contained ca. 2.45 +/- 0.07% tyrosine-bound [35S]sulfate with the rest being presumably carbohydrate-bound. [32P]-Phosphate-labeled gp 80, on the other hand, was found to contain serine-O phosphate as the predominant phosphorylated amino acid residue. Employing the affinity gel fractionation technique, it was shown that gp 80 exhibited binding affinities toward heparin and fibrin. Binding of gp 80 to heparin-agarose or fibrin-Sepharose, however, was inhibited in the presence of added fibronectin or the monoclonal antibody. Tryptic peptide mapping revealed common peptide spots between fibronectin and the three subunits of gp 80. Furthermore, Western blot analysis showed that fibronectin could be recognized and bound by anti-gp 80 antibodies. These results indicate that gp 80 bears both structural and functional similarities to the C-terminal portion of the fibronectin molecule. PMID- 1897962 TI - Two immunologically different isozymes of ascorbate peroxidase from spinach leaves. AB - Two isozymes of ascorbate peroxidase (AP) from spinach leaves were separated by hydrophobic chromatography and designated AP-I and AP-II. They had similar molecular weights of about 31,000, as determined by gel-filtration, and showed high specificity for ascorbate. One of the two isozymes (AP-II) was purified to homogeneity by SDS-PAGE. Immunoblotting confirmed that antiserum against AP-II reacted with AP-II but not with AP-I. This antiserum inhibited the activity of AP II, but not that of AP-I. The amino acid composition and partial amino acid sequence of AP-II were determined. PMID- 1897963 TI - Lipid transfer particle-catalyzed transfer of lipoprotein-associated diacylglycerol and long chain aliphatic hydrocarbons. AB - Following injection of [1-14C]acetate into the sphinx moth, Manduca sexta, radiolabel was incorporated into lipid components of the major hemolymph lipoprotein, adult high density lipophorin (HDLp-A). Analysis of the labeled lipids by thin layer chromatography and radiochromatogram scanning revealed incorporation of radioactivity into the diacylglycerol (DAG) and hydrocarbon components as well as a third lipid fraction of unknown identity. Lipid transfer experiments were carried out using 14C-lipid HDLp-A and human low density lipoprotein (LDL) as donor/acceptor substrates and M. sexta lipid transfer particle (LTP) as catalyst. In control incubations lacking LTP, nearly all of the radiolabeled lipid remained associated with HDLp-A. LTP, however, induced a time dependent vectorial transfer of radiolabeled lipid from HDLp-A to LDL. Lipid analysis of the LDL fraction, reisolated following the transfer reaction, revealed that labeled lipid components originally associated with HDLp-A were present in the acceptor LDL particles. The recovery of radiolabeled hydrocarbon associated with LDL demonstrates the capacity of LTP to facilitate transfer of these long chain, extremely hydrophobic, lipids and suggests LTP may function as a mediator of hydrocarbon transport and metabolism in vivo. When acceptor LDL particles were analyzed prior to complete transfer of HDLp-A-associated lipid it was observed that DAG was transferred preferentially during the initial stages of the reaction after which hydrocarbon transfer increased. This result suggests that LTP may have a lipid substrate preference for DAG versus hydrocarbon. Alternatively the observed preference for DAG may be a function of the relative accessibility of the substrates within the donor lipoprotein. In other experiments it was demonstrated that, unlike other lipids associated with HDLp-A, free fatty acid spontaneously transfers to LDL in the absence of lipid transfer catalyst. PMID- 1897964 TI - Identity of mucin's "118-kDa link protein" with fibronectin fragment. AB - Human and rat intestinal mucin was purified by equilibrium density gradient centrifugation and Sepharose 2B chromatography according to M. Mantle, D. Mantle, and A. Allen (1981, Biochem. J. 195, 277-285) and analyzed using mucin, DNA, and fibronectin-specific antibodies in dot-blot, ELISA, and Western blotting. The 118 kDa component of the mucins and the 118-kDa fragment of fibronectin from the same source displayed affinity for concanavalin A and immunoreacted with fibronectin antibodies. The amino acid and carbohydrate compositions of the 118-kDa peptide electroeluted by gel electrophoresis of mucin and fibronectin preparations were identical within each pair of glycopeptides and closely resembled the "link protein component" of human and rat intestinal mucin preparations of R. E. F. Fahim, R. D. Specian, G. G. Forstner, and J. F. Forstner (1987, Biochem. J. 243, 631-640) and M. Mantle and G. Stewart (1989, Biochem. J. 259, 631-640). We therefore conclude that the "link protein" claimed to be an integral part of mucus glycoproteins in actuality is the 118-kDa fragment of fibronectin. PMID- 1897965 TI - pH-induced reorganization of synaptic membrane as revealed by fluorescence anisotropy and energy transfer. AB - Two fluorescent probes, 2-(9-anthroyloxy)stearate and 12-(9-anthroyloxy)stearate, were used to investigate the effects of the neutralization of membrane charges on the organization of synaptic plasma membrane. Steady state fluorescence anisotropy measurements showed that a pH decrease provoked a rigidification of the synaptic membrane surface, whereas the bilayer core remained unaffected. The same effect was observed with negatively charged lipid vesicles. The relative distribution of proteins and the probes was estimated by fluorescence energy transfer from protein tryptophans to fluorescent probes: a pH decrease provoked an increase of the energy transfer, which was most pronounced with the surface probe, indicating an average closer packing between proteins and the probes. The modifications induced by a pH decrease were temperature dependent and were most marked at low temperatures. The results suggest that neutralization of the membrane charges provoked a redistribution of both membrane lipids and proteins. These findings are discussed in terms of a heterogeneous distribution of these membrane components. PMID- 1897966 TI - Structures of glycophosphosphingolipids of Tritrichomonas foetus: a novel glycophosphosphingolipid. AB - The glycophosphosphingolipids of Tritrichomonas foetus, an aerotolerant parasite of the urogenital tract of cattle, have been characterized by a combination of metabolic labeling, chromatography, and tandem mass spectrometry. The acidic glycolipid fraction of T. foetus obtained by DEAE Sephadex A-25 column chromatography was subfractionated by high performance thin layer chromatography and the component lipids were purified by high performance liquid chromatography. Two nonsaponifiable lipid fractions, designated TF1 and TF2, could be metabolically labeled with [3H]myoinositol and [32P]orthophosphate. [3H]Fucose and [14C]ethanolamine were preferentially incorporated into the TF1 fraction. TF1 was partially hydrolyzed by alpha-fucosidase. Both TF1 and TF2 contain ceramides, the most abundant having either sphinganine or sphingosine and a 16:0 N-acyl group. TF2 contains inositolphosphoceramides. TF1, on the other hand, contains three closely related components, in each of which fucose is linked to inositol diphosphate with one of the phosphates linked to the ceramide moiety and the other phosphate either free or linked to ethanolamine or N-acetylethanolamine. TF1 appears to be a novel class of glycophosphosphingolipid which shows some structural similarities to the glycosylphosphatidylinositol anchors of eukaryotic membrane proteins. PMID- 1897967 TI - Cysteine sulfinic acid decarboxylase activity in response to thyroid hormone administration in rats. AB - The modulation of hepatic and renal cysteine sulfinic acid decarboxylase (EC 4.1.1.29) activities by triiodothyronine (T3) was studied in a series of experiments. In a dose--response study, hepatic cysteine sulfinic acid decarboxylase activity (CSAD) was depressed by 65% and renal activity was increased threefold in rats injected with 100 micrograms T3/100 g body wt for 7 days when compared to rats injected with 0.3 micrograms T3/100 g body wt. Western blot analysis indicated that these changes in CSAD activity were due to changes in the quantity of CSAD protein. Changes in hepatic and renal activities were not evident until 24 h after T3 administration. In response to T3 clearance, hepatic and renal CSAD activities approached euthyroid values 4-7 days after cessation of T3 injections although serum T3 concentrations were no different from euthyroid values 48 h after T3 injections were stopped. These data indicate that thyroid hormone effects persist after T3 clearance. The response of CSAD to thyroid status may be related to its role in taurine biosynthesis. PMID- 1897969 TI - A single cyclohexadienyl dehydratase specifies the prephenate dehydratase and arogenate dehydratase components of one of two independent pathways to L phenylalanine in Erwinia herbicola. AB - Dual biosynthetic pathways diverge from prephenate to L-phenylalanine in Erwinia herbicola, the unique intermediates of these pathways being phenylpyruvate and L arogenate. After separation from the bifunctional P-protein (one component of which has prephenate dehydratase activity), the remaining prephenate dehydratase activity could not be separated from arogenate dehydratase activity throughout fractionation steps yielding a purification of more than 1200-fold. The ratio of activities was constant after removal of the P-protein, and the two dehydratase activities were stable during purification. Hence, the enzyme is a cyclohexadienyl dehydratase. The native enzyme has a molecular mass of 73 kDa and is a tetramer made up of identical 18-kDa subunits. Km values of 0.17 mM and 0.09 mM were calculated for prephenate and L-arogenate, respectively. L-Arogenate inhibited prephenate dehydratase competitively with respect to prephenate, whereas prephenate inhibited arogenate dehydratase competitively with respect to L-arogenate. Thus, the enzyme has a common catalytic site for utilization of prephenate or L-arogenate as alternative substrates. This is the first characterization of a purified monofunctional cyclohexadienyl dehydratase. PMID- 1897968 TI - Fluorescent labeling of the nucleotide site in cytosolic rat liver phosphoenolpyruvate carboxykinase. AB - Reaction of rat liver phosphoenolpyruvate carboxykinase (GTP: oxaloacetate carboxy-lyase (transphosphorylating), EC 4.1.1.32) with the alkylating fluorescent probe N-(iodoacetylaminoethyl)-5-naphthylamine-1-sulfonic acid (1,5-I AEDANS), results in complete loss of enzymatic activity. One mole of the fluorescent reagent is incorporated per mole of the inactivated enzyme. When the modification is carried out in the presence of GDPMn, the enzyme retains 97% of its activity with almost no incorporation of label. The specificity of the reaction is further supported by the detection of a unique fluorescent peptide from the trypsin-treated modified enzyme. Fluorescence emission of enzyme-bound AEDANS shows a broad band centered at 470 nm and presents a monoexponential decay with a lifetime of 19 ns. These data indicate that the probe-binding site is considerably less polar than water and similar in polarity to ethanol. Anisotropy determinations give evidence for restricted rotational freedom for AEDANS bound to the rat carboxykinase, while acrylamide quenching studies reveal limited accessibility to the probe site. The results are consistent with specific labeling of rat liver phosphoenolpyruvate carboxykinase at or near the GDP site. The characteristics of the nucleotide-binding sites of rat liver and yeast (ATP) phosphoenolpyruvate carboxykinase are compared. PMID- 1897970 TI - The use of 6-(difluoromethyl)indole to study the activation of indole by tryptophan synthase. AB - 6-(Difluoromethyl)indole has been characterized and developed as a probe for the turnover of indole by the bifunctional enzyme, tryptophan synthase (alpha 2 beta 2). The neutral form of the indolyl species undergoes a slow and spontaneous hydrolysis to produce 6-formylindole with a rate constant (k1) of 0.0089 +/- 0.0001 min-1. The overall rate is independent of pH in the range of 3.5-10.5. Above pH 10.5, the observed rate increases are due to the high reactivity of the anionic form of the indole; deprotonation at N-1 accelerates hydrolysis by 10(4) fold (k2, 97 +/- 2 min-1). The magnitude of this effect provides a technique for detecting the formation or stabilization of the anionic form of indole. 6 (Difluoromethyl)indole is recognized and processed by the beta subunit of tryptophan synthase. Selective inactivation of the beta subunit prevents enzymatic processing of 6-(difluoromethyl)indole. Chromatographic isolation and mass spectral analysis has identified 6-(difluoromethyl)tryptophan as the sole turnover product of the indolyl substrate. The lack of enzyme-promoted dehalogenation does not exclude the formation of an indole anion during turnover but rather the data suggest that rapid carbon-carbon bond formation (greater than 5300 min-1) prevents the accumulation of this anion. PMID- 1897971 TI - Biosynthesis of choline plasmalogens in neonatal rat myocytes. AB - The alk-1-enyl bond in plasmenylethanolamine is formed from plasmanylethanolamine by the action of a microsomal cytochrome b5-dependent desaturase. However, the origin of the alk-1-enyl linkage in plasmenylcholine, a significant subclass of phospholipids in heart tissues of certain animal species, is not yet known. We have used neonatal rat myocytes as a model to study the biosynthesis of plasmenylcholine in the present studies since they have a phospholipid composition and subclasses of 1,2-diradyl-sn-glycero-3-phosphocholine (-GPC) similar to those of neonatal rat hearts. When equal concentrations of [3H]hexadecyllyso-GPC or [3H]hexadecyllyso-sn-glycero-3-phosphoethanolamine ( GPE) are incubated under identical conditions with myocytes for 4, 12, and 24 h, the rate of plasmenylcholine formation is faster from [3H]hexadecyllyso-GPE than from [3H]hexadecyllyso-GPC. Also, when [3H]alkyllyso-GPC and alkyllyso-[N-methyl 14C]GPC are incubated with rat myocytes for various times up to 24 h, the 3H/14C ratio in the diacyl-GPC plus alkylacyl-GPC fraction and alkyllyso-GPC remains relatively constant (3H/14C = 2.7), whereas the 3H/14C of plasmenylcholine increases from 0.3 at 2 h to 1.7 after 24 h. Finally, when the rat myocytes are prelabeled with [3H]alkyllyso-GPE for 4 h and then reincubated with either [14C]choline or [14C]methionine for 1 or 3 h, both [14C]choline and [14C]methionine are incorporated into plasmenylcholine, except the 14C/3H is much higher (5- to 15-fold) in the [14C]choline-labeled plasmenylcholine than in the [14C]methionine-labeled plasmenylcholine. Collectively, our data show plasmenylcholine is not directly derived from plasmanylcholine or lysoplasmanylcholine, but instead is formed from plasmenylethanolamine via some type of hydrolytic exchange mechanism, and the contribution of plasmenylethanolamine through methylation to the synthesis of plasmenylcholine is of limited capacity. PMID- 1897972 TI - The reductive half-reaction in acyl-CoA oxidase from Candida tropicalis: interaction with acyl-CoA analogues and an unusual thioesterase activity. AB - A series of acyl-CoA analogues has been used to probe the substrate binding site and reductive half-reaction of acyl-CoA oxidase from the alkane utilizing yeast Candida tropicalis. Alkyl-SCoA thioethers, from octyl- to hexadecyl-SCoA, bind to the oxidase with progressively larger spectral perturbation of the flavin chromophore and with an incremental binding energy of about 260 cal/methylene group. The hydrocarbon binding subsite for acyl-CoA oxidase appears extensive and only weakly hydrophobic. CoA binding per se appears to contribute about 2.8 kcal to the observed binding energy. A number of acyl-CoA analogues such as 3-thia acyl-, 3-oxa-acyl-, trans-3-enoyl-, and 3-keto-acyl-CoA derivatives form charge transfer complexes with the oxidase, but these long wavelength bands are both less pronounced and much less stable than those encountered with the acyl-CoA dehydrogenases. This instability reflects an intrinsic thioesterase activity of the oxidase which is observed with those ligands forming enolate to oxidized flavin charge-transfer complexes, but not with normal substrates such as palmitoyl-CoA. Chemical precedent suggests that these enzyme-bound enolates eliminate CoA via a ketene intermediate. The differences in behavior between acyl CoA oxidase and dehydrogenase toward the ligands used in this work are discussed in terms of the need to exclude oxygen from productive encounters with substrate reduced dehydrogenase. PMID- 1897973 TI - Purification and characterization of the monoterpene cyclase gamma-terpinene synthase from Thymus vulgaris. AB - The monoterpene cyclase, gamma-terpinene synthase, from Thymus vulgaris (thyme) leaves was purified to apparent homogeneity by isoelectric focusing and dye ligand, anion-exchange, hydrophobic interaction, and gel permeation chromatography. The enzyme has a native molecular weight of 96,000 as determined by gel permeation chromatography, and exhibited a specific activity of 538 nmol/h.mg protein (turnover number of approximately 0.01/s). Sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed the enzyme to be composed of two apparently identical subunits of Mr approximately 55,000. The protein was very hydrophobic, and possessed a pI value of 4.85 as determined by isoelectric focusing. Maximum activity was observed at pH 6.8 in the presence of 20 mM Mg2+; 5 mM Mn2+ could support catalysis, albeit at a much lower rate. The Km value for the substrate, geranyl pyrophosphate, was 2.6 microM. Cyclase activity was inhibited by cysteine- and histidine-directed reagents. Purified gamma-terpinene synthase also possessed the ability to cyclize geranyl pyrophosphate to small amounts of alpha-thujene and to lesser quantities of myrcene, alpha-terpinene, limonene, linalool, terpinen-4-ol, and alpha-terpineol, all of which appear to be coproducts of the reaction sequence leading to gamma-terpinene. In general properties, the gamma-terpinene synthase from thyme leaves resembles other monoterpene cyclases as well as sesquiterpene and diterpene cyclases. PMID- 1897974 TI - Molecular organization and dynamics of the outer membrane of Salmonella thyphimurium mutant strains detected by frequency domain fluorometry. AB - The fluorescence decay of 1,6-diphenyl-1,3,5-hexatriene (DPH) in the outer membrane bilayer of two mutant strains of Salmonella thyphimurium, i.e., SH 5014 and SH 6261, at different temperatures was analyzed in terms of continuous Lorentzian lifetime distributions. The results were compared with those obtained for the free fluorophore in an isotropic nonviscous solvent. The incorporation of DPH in the outer membrane fragments resulted in a broadening of the lifetime distribution which was attributed to the microenvironmental heterogeneity of the membrane bilayer for the extrinsic fluorophore. The differences observed between the two types of membrane bilayers were interpreted in terms of a different molecular organization and, to a lesser extent, in terms of a different fluidity. The comparison between the DPH lifetime distributions obtained using two different excitation wavelengths, i.e., 280 and 350 nm, suggested that the structural organization of the membrane domains, which are richest in proteins, is almost identical in the two examined mutant strains. This observation indicates that the different susceptibility of the two mutant strains toward phagocytosis and complement-mediated lytic action may depend on the molecular organization and dynamics of the lipid regions far from those containing proteins. PMID- 1897975 TI - Correlation between the "low"-salt-induced increase in the F730/F685 fluorescence emission ratio at 77 K in isolated chloroplasts, and the organization of chlorophyll in photosystem I pigment-protein complexes of thylakoids. AB - Isolated pea or spinach chloroplasts suspended in "high"-salt phosphate buffer exhibit a low F730/F685 fluorescence emission ratio at 77 K; in contrast, removal of cations by incubation in "low"-salt Tricine buffer induces a drastic increase in the F730/F685 ratio. Parallel to the F730/F685 ratio increase, a gradual organization of chlorophyll (Chl) in the pigment-protein complexes of the Photosystem I, chlorophyll-protein complex Ia, and light-harvesting complex I (LHC-I), is observed. The kinetics of the two processes are closely correlated, all changes being completed within 5-10 min from Tricine addition. On the other hand, the inability of low-salt Tricine to induce any changes in the F730/F685 ratio in bean plastids, isolated and suspended in high-salt phosphate buffer, correlates with the lack of extensive changes in the organization of the Photosystem I complexes, and more specifically of LHC-I. The latter is attributed to the higher stability of complexes in bean, arising from stronger association of thylakoids in grana stacks in this species; this is probably due to higher levels of residual divalent cations present in the isolated thylakoids of bean compared to pea (or spinach). The results suggest that the F730/F685 ratio changes, observed in chloroplasts by manipulation of their ionic environment, reflect modulation of Chl organization within the pigment-protein complexes of the photosynthetic units. PMID- 1897976 TI - Quantitative evaluation of solution equilibrium binding interactions by affinity partitioning: application to specific and nonspecific protein-heparin interactions. AB - A variation of the quantitative affinity chromatography (QAC) method of Winzor, Chaiken, and co-workers for the analysis of protein-ligand interactions has been developed and used to characterize sequence-specific and nonspecific protein heparin interactions relevant to blood coagulation. The method allows quantitation of the binding of two components, A and B, from the competitive effect of one component, B, on the partitioning of the other component, A, between an immobilized acceptor phase and solution phase at equilibrium. Under the conditions employed, the differences in total A concentrations yielding an equivalent degree of saturation of the immobilized acceptor in the absence and presence of B defines the concentration of A bound to B in solution, thereby enabling conventional Scatchard or nonlinear least-squares analysis of the A-B equilibrium interaction. Like the QAC method, quantitation of the competitor interaction does not depend on the nature of the affinity matrix interaction, which need only be described empirically. The additional advantage of the difference method is that only the total rather than the free competitor ligand concentration need be known. The method requires that the partitioning component A be univalent, but allows for multivalency in the competitor, B, and can in principle be used to study binding interactions involving nonidentical, interacting, or nonspecific overlapping sites. Both the binding constant and the stoichiometry for the specific antithrombin-heparin interaction as well as the apparent binding constant for the nonspecific thrombin-heparin interaction at low thrombin binding densities obtained using this technique were in excellent agreement with values determined using spectroscopic probes. PMID- 1897977 TI - Evidence against tight channelling of NADH in hepatocytes. AB - Tritiated substrates at tracer levels were incubated with rat hepatocytes plus 10 mM L-lactate, and the yields of tritium in glucose and water, as well as the tritium distribution on C-6 and C-4 of glucose, determined. Substrates of cytosolic type A NAD-linked dehydrogenases showed some preferential labeling of C 6 of glucose (the pathway involving type A malate dehydrogenase), whereas substrates of cytosolic type B NAD-linked dehydrogenases showed some preferential labeling of C-4 of glucose (the pathway involving type B glyceraldehyde-3P dehydrogenase). The results found are consistent with a classical diffusion model of NADH metabolism, and are at odds with the Srivastava hypothesis (based on isolated enzyme studies) which indicated that direct transfer of NADH can occur between many NAD-linked enzymes but only when they are of opposite (A or B) specificity. PMID- 1897978 TI - Purification and characterization of three forms of differently glycosylated recombinant human granulocyte-macrophage colony-stimulating factor. AB - We have purified recombinant human granulocyte-macrophage colony-stimulating factor (hGM-CSF) produced in human lymphoblastoid Namalwa cells. From the results of tunicamycin treatment and N-glycosidase F digestion, it was demonstrated that Namalwa-derived hGM-CSF was highly glycosylated at two potential N-glycosylation sites and several O-glycosylation sites as previously shown for naturally occurring hGM-CSF. We classified the hGM-CSF molecules into three groups according to the molecular weight corresponding to the degree of N-glycosylation: the molecules with two N-glycosylation sites occupied (designated 2N), the molecules with either site glycosylated (1N), and the molecules lacking N glycosylation (0N). Despite such varied degrees of N-glycosylation, almost all molecules were O-glycosylated. To investigate the role of carbohydrate moieties of hGM-CSF, we isolated each form of hGM-CSF and examined its biological properties. The 2N-type showed 200-fold less in vitro specific activity compared with unglycosylated Escherichia coli-derived hGM-CSF, although the activity of the 0N-type was equivalent to that of the E. coli-derived material. The 1N-type showed an intermediate level of activity. However, in terms of clearance from blood circulation in the rat, the 2N-type showed a half-life five times longer than that of the 0N-type and E. coli-derived hGM-CSF. From these findings, we concluded that N-linked carbohydrate moieties of hGM-CSF play conflicting physiological roles in the efficacy of the protein in vivo but that O-linked carbohydrate moieties do not have such effects. PMID- 1897979 TI - Site-directed mutagenesis of glutathione S-transferase YaYa: nonessential role of histidine in catalysis. AB - A cDNA encoding a rat liver glutathione S-transferase Ya subunit has been expressed in Escherichia coli and the expressed enzyme purified to homogeneity. In order to examine the catalytic role of histidine in the glutathione S transferase Ya homodimer, site-directed mutagenesis was used to replace all three histidine residues (at positions 8, 143, and 159) by other amino acid residues. The replacement of histidine 8 or histidine 143 with valine did not affect the 1 chloro-2,4-dinitrobenzene-conjugating activity nor the isomerase activity. However, the replacement of histidine with valine at position 159 produced the mutant GST which exhibited only partial activity. A greater decrease in catalytic activity was observed by histidine----tyrosine or histidine----lysine replacement at position 159. On the other hand, the histidine 159----asparagine mutant retained full catalytic activity. Our results indicate that histidine residues in the Ya homodimer are not essential for catalytic activity. However, histidine 159 might be critical in maintaining the proper conformation of this enzyme since replacement of this amino acid by either lysine or tyrosine did result in significant loss of enzymatic activity. PMID- 1897980 TI - Ceratitis capitata brain adenylate cyclase and its membrane environment. AB - Adenylate cyclase activation by GTP and octopamine as well as basal activity (in the presence of Mg2+) have been studied as a function of membrane structure in plasma membranes from brain of the dipterous Ceratitis capitata. Benzyl alcohol and lidocaine, but not phenobarbital, inhibited the three activities to the same extent. Triton X-100-solubilized adenylate cyclase was also inhibited by benzyl alcohol and lidocaine, but not by phenobarbital. Results could be explained by an effect on the catalytic unit lipid environment, which would be maintained after solubilization, counteracting the effect of these drugs to facilitate lateral diffusion and coupling of adenylate cyclase components in the lipid bilayer. The observation that the insect adenylate cyclase is relatively insensitive to changes in bulk bilayer fluidity is strengthened by the absence of effect of phenobarbital on enzyme activities. Indeed, this compound was as active as lidocaine or benzyl alcohol in increasing bulk membrane fluidity. The response of C. capitata adenylate cyclase to changes in membrane fluidity is different from that recorded in mammalian systems. This may be functionally important and result from the fact that insects are not warm-blooded. PMID- 1897982 TI - Human red blood cell-mediated metabolism of leucovorin [(R,S)5 formyltetrahydrofolate]. AB - The ability of human blood in vitro, and partially purified red blood cells, to metabolize leucovorin, or 5-formyltetrahydrofolate, has been examined. A radioenzymatic assay based upon entrapment of 5,10-methylenetetrahydrofolate, and other reduced folates after cycling to this form, into a stable ternary complex with thymidylate synthase and tritiated 5-fluoro-2'-deoxyuridine-5'-monophosphate was used to estimate reduced folate metabolites. Incubation of whole blood samples with (R,S)5-formyltetrahydrofolate resulted in a time- and concentration dependent extracellular accumulation of the reduced folates, 5 methyltetrahydrofolate, tetrahydrofolate, 10-formyltetrahydrofolate, and 5,10 methylenetetrahydrofolate. While accumulation with time was nonlinear, the tetrahydrofolate pool showed the greatest overall increase in concentration. 5 Methyltetrahydrofolate, which was the only reduced folate detected in plasma prior to introduction of (R,S)5-formyltetrahydrofolate, accumulated more slowly than tetrahydrofolate. 10-Formyltetrahydrofolate and 5,10 methylenetetrahydrofolate accumulated even more slowly but exhibited nonlinear kinetic patterns similar to those of tetrahydrofolate and 5 methyltetrahydrofolate. When blood cells were removed by centrifugation, a complete loss of metabolic activity was observed. Exposure of purified red blood cells to (R,S)5-formyltetrahydrofolate resulted in accumulation of extracellular reduced folates that was similar to that in whole blood samples while partially purified white blood cells exhibited little activity. Metabolism of the (S) diastereomer of 5-formyltetrahydrofolate accounted for essentially all of the observed extracellular accumulation of reduced folates. We propose that red blood cell-mediated metabolism of 5-formyltetrahydrofolate could, in part at least, account for reduced folate accumulation in plasma when leucovorin is administered to humans. PMID- 1897981 TI - Increased expression of cytochrome P450 IIIA2 in male rat liver after dietary vitamin A supplementation. AB - In this study dietary vitamin A supplementation (25 IU/g diet) was assessed for its effect on hepatic microsomal P450 content and on P450 enzyme-specific drug oxidase activities in rats. Intake of the supplemented diet by male rats over a 15-week period resulted in a fivefold increase in hepatic vitamin A stores over those measured in control liver from rats that received a balanced diet without vitamin A supplementation. Serum retinol was unchanged and there was no evidence of hepatocellular injury in any of the animals. There was a 26% increase in P450 content in vitamin A-supplemented rat liver and regioselective androst-4-ene-3,17 dione (androstenedione) and progesterone hydroxylation revealed changes in several P450 pathways. Thus, androstenedione 16 alpha-hydroxylation (P450 IIC11 mediated) and progesterone 21-hydroxylation (P450 IIC6-mediated) were decreased slightly to 80 and 74% of respective control activities while P450 IIA1/2 dependent androstenedione 7 alpha-hydroxylation was slightly increased. In contrast, the 6 beta-hydroxylations of androstenedione and progesterone were increased to 169 and 152% of control following dietary supplementation. Kinetic analysis of androstenedione 6 beta-hydroxylation revealed an increase in maximal reaction velocity (Vmax 4.00 +/- 0.47 vs 2.20 +/- 0.10 nmol/min/mg protein) but the Km was unchanged, suggesting an increase in enzyme concentration. Consistent with this assertion, immunoquantitation of the steroid 6 beta-hydroxylase, P450 IIIA2, revealed a 158% increase in the microsomal expression of this enzyme (9.8 +/- 2.7 vs 6.2 +/- 1.3 ng/micrograms microsomal protein). From these studies it now seems clear that vitamin A, as a dietary additive in nontoxic doses, has the capacity to alter the activity of hepatic microsomal drug oxidases by modulating the expression of P450 enzymes. PMID- 1897983 TI - Expression of growth hormone-releasing factor analog Leu27GRF(1-44)OH in Escherichia coli: purification and characterization of the expressed protein. AB - A recombinant plasmid has been constructed to direct the synthesis of Leu27GRF(1 44)OH in Escherichia coli as a fusion protein containing a hexa-His tail followed by amino acids 1-99 of interferon-gamma and a methionine residue at the N terminal. The expression of the 18-kDa fusion protein (H6GAMGRF) was induced by isopropylthiogalactoside treatment and the protein accumulated as insoluble aggregates in inclusion bodies. The protein aggregates were solubilized in 6 M guanidine-HCl and purified directly by affinity chromatography on a Nichelate column. The growth hormone-releasing factor (GRF) moiety was released from the fusion protein by cyanogen bromide cleavage and purified to homogeneity by anion exchange chromatography followed by reverse-phase chromatography. The identity of the GRF peak was determined by comparing its retention time with that of synthetic Leu27GRF(1-44)OH. The purified material was further characterized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, N-terminal sequencing, and amino-acid analysis. The recombinant-derived product and the synthetic compound showed identical reactivities toward anti-GRF polyclonal antibodies and were essentially equipotent as determined by an in vitro biological assay for growth hormone-releasing activity. PMID- 1897984 TI - Complete amino acid sequence of the type II isozyme of rat hexokinase, deduced from the cloned cDNA: comparison with a hexokinase from novikoff ascites tumor. AB - The 917-residue amino acid sequence of the Type II isozyme of rat hexokinase has been deduced from the nucleotide sequence of cloned cDNA. The sequences of 197 nucleotides in the 5' untranslated region and 687 bases of the 3' untranslated region have also been determined. A region of overlap between two discrete cDNA clones was confirmed by isolation and sequencing of a genomic DNA clone that spanned the region. Within this region, the 634-nucleotide coding sequence was divided into three exons, each of 150-250 nucleotides; these results suggest that the gene encoding Type II hexokinase is likely to be quite complex. There is extensive similarity between the sequences of the N- and C-terminal halves of the Type II isozyme, as previously seen with the Type I and III isozymes; this is consistent with the view that these enzymes evolved by a process of gene duplication and fusion. A cDNA encoding the entire C-terminal half of a hexokinase from Novikoff ascites tumor cells was also isolated and found to be identical to a cDNA encoding the corresponding region of the Type II isozyme of skeletal muscle. Northern analysis indicated that a single mRNA, approx 5200 nucleotides in length, encoded both the skeletal muscle and the tumor enzymes. These results do not support previous speculation that the hexokinase isozymes of normal tissue are distinct from those of tumors, and suggest the possibility that post-translational modifications of a single protein species might account for apparent differences between the isozymes of normal and tumor tissues. PMID- 1897985 TI - Intra- and intermolecular electron transfer processes in redox proteins. PMID- 1897986 TI - A constitutive form of guinea pig liver cytochrome P450 closely related to phenobarbital inducible P450b(e). AB - In order to provide evidence that a cytochrome P450 belonging to the IIB subfamily is expressed as a constitutive form in the guinea pig, we tried to purify an isozyme from liver microsomes of untreated guinea pigs by assessing its reactivity with anti-P450b antibody in the present study. One form of cytochrome P450, named P450GP-1, was obtained. The minimum molecular weight of this isozyme was estimated to be 52,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The amino terminal sequence up to the 33rd amino acid of P450GP 1 was determined. As expected, comparison of the amino acid sequence with those of cytochrome P450 isozymes from other species reported so far indicated that P450GP-1 was highly homologous to P450s categorized in the IIB subfamily; that is, 67% similarity to rat P450b, 82% to rabbit LM2, 76% to dog PBD-2, 70% to mouse pf 3/46, and 73% to human IIB1. On the other hand, P450GP-1 showed only low similarity, less than 41%, to other cytochrome P450s of the II subfamily and those of the I, III, and IV families. Affinity of P450GP-1 to anti-P450b immunoglobulin G was confirmed to be comparable with that of a principal antigen, P450b. Immunoblot analysis revealed that P450GP-1 in the guinea pig liver microsomes was induced by phenobarbital treatment, but the increase was not as large as in the rat. P450GP-1 efficiently catalyzed benzphetamine N demethylation, strychnine 2-hydroxylation, and testosterone 16 beta hydroxylation, all of which are also catalyzed by P450b. Based on these results, it was strongly suggested that the IIB-type of cytochrome P450 in guinea pigs, at least one of them, is a constitutive form which is moderately induced by phenobarbital. PMID- 1897987 TI - Reduction (dethiolation) of protein mixed-disulfides; distribution and specificity of dethiolating enzymes and N,N'-bis(2-chlorethyl)-N-nitrosourea inhibition of an NADPH-dependent cardiac dethiolase. AB - The S-thiolated proteins phosphorylase b (Phb) and carbonic anhydrase III (CAIII) were prepared with [3H]glutathione in a reaction initiated with diamide. These substrates were used to measure the rate of reduction (dethiolation) of protein mixed-disulfides by enzymes with properties similar to those of thioredoxin and glutaredoxin. This enzyme activity is termed a dethiolase since the identities of the enzymes are still unknown. The dethiolation of either S-[3H]glutathiolated Phb or S-[3H]glutathiolated CAIII was employed in tissue assays and for study of two partially purified dethiolases from cardiac tissue. NADPH-dependent dethiolase activity was most abundant except in rat liver and muscle. Total dethiolase activity was approximately 10-fold higher in neutrophils, 3T3-L1 cells, and Escherichia coli than in other sources. Rat skeletal muscle had 3- to 4-fold higher dethiolase activity than rat heart or liver. These data indicate that protein dethiolase activity is ubiquitous and that normal expression of the two dethiolase activities varies considerably. A partially purified cardiac NADPH dependent dethiolase acted on Phb approximately 1.5 times faster than CAIII, and a glutathione (GSH)-dependent dethiolase acted on Phb 3 times faster than CAIII. The Km for glutathione for the GSH-dependent dethiolase was 15 microM with Phb as substrate and 10 microM with CAIII. Thus, the GSH-dependent dethiolase is probably not affected by normal changes in the cardiac glutathione content (normally approximately 3 mM). Partially purified cardiac NADPH-dependent dethiolase was inactivated by BCNU (N,N'-bis(2-chloroethyl)-N-nitrosourea) and the GSH-dependent dethiolase was unaffected under similar conditions. In a soluble extract from bovine heart, 200 microM BCNU inhibited NADPH-dependent dethiolase by more than 60% but did not affect GSH-dependent activity. These results demonstrate that BCNU is a selective inhibitor of the NADPH-dependent dethiolase. PMID- 1897989 TI - Plant thioredoxin h: an animal-like thioredoxin occurring in multiple cell compartments. AB - Thioredoxin h has been purified to electrophoretic homogeneity from spinach roots using a procedure devised for leaves. The root thioredoxin (h2 form) differed from chloroplast and animal thioredoxins in showing an atypical active site (Cys Ala-Pro-Cys) but otherwise resembled animal thioredoxin in structure. Sequence data for a total of 72 residues of spinach root thioredoxin h2 (about 69% of the primary structure) showed 43-44% identity with rabbit and rat thioredoxin. Analysis of cell fractions from the endosperm of germinating castor beans revealed that thioredoxin h occurs in the cytosol, endoplasmic reticulum, and mitochondria. The present findings demonstrate a similarity between plant thioredoxin h and animal thioredoxins in structure and intracellular location and raise the question of whether these proteins have similar functions. PMID- 1897988 TI - Leukotriene A4 hydrolase in the human B-lymphocytic cell line Raji: indications of catalytically divergent forms of the enzyme. AB - Leukotriene A4 hydrolase was purified 1400-fold, with an approximate yield of 25%, to apparent homogeneity from the human B-lymphocytic cell line Raji. The purification included ammonium sulfate precipitations followed by anion exchange, hydrophobic interaction, and molecular exclusion fast protein liquid chromatography. Kinetic properties at 2 degrees C varied between different enzyme preparations. Two patterns were observed, one with a Km of about 12 microM and Vmax of about 1.1 mumol LTB4/mg protein/min which correlated well with the properties of the human leukocytic LTA4 hydrolase. In other enzyme preparations a higher catalytic activity was observed. These enzyme batches did not obey Michaelis-Menten kinetics but were compatible with a mixture of enzymatic species. Heat treatment (60 degrees C) led to a time-dependent decline in catalytic activity. However, certain enzyme preparations contained a subfraction of enzymatic activity which was more resistant to heat treatment, yielding a biphasic inactivation pattern. It is thus suggested, on the basis of the kinetic properties and the heat-inactivation pattern, that these enzyme preparations contained an addition form of LTA4 hydrolase. PMID- 1897990 TI - Exchange of 20-kDa myosin light chain-bound phosphate during sustained contraction of arterial smooth muscle. AB - K(+)-contracted porcine carotid arterial muscles containing phosphorylated 20-kDa myosin light chains (LC) were exposed to carrier-free [32P]orthophosphate in K(+) stimulating solution during sustained contraction. The covalently bound LC phosphate was completely replaced by [32P]phosphate, indicating that myosin light chain phosphatase and kinase have ready access to the bound phosphate during the sustained contraction. On average, 0.38 mol [32P]phosphate was incorporated per mole LC during the sustained K+ contraction. This value was about half of the maximal value for [32P]phosphate incorporation into LC, 0.74 mol/mol, in muscles contracted with K+ for 1 min. Assuming that sustained contraction involves the maximal number of cross-bridges attached to actin, the data suggest that half of the attached cross-bridges contain phosphorylated LC. PMID- 1897992 TI - Examination of phenylalanine microenvironments in proteins by second-derivative absorption spectroscopy. AB - We have employed near ultraviolet derivative absorption spectroscopy to study the microenvironments of phenylalanine residues in proteins. The use of second derivative uv spectra in the 250- to 270-nm range effectively suppresses spectral contributions from tryptophan and tyrosine residues. Fitting a polynomial to the numerically calculated second-derivative spectrum allows precise determination of the position of the negative derivative peak near 258 nm. This position is shown to be correlated with the polarity of the microenvironments of phenylalanine residues. This approach allows monitoring of changes in the state of phenylalanine side chains during folding/unfolding of the proteins. In addition, this method permits perturbation of protein samples with ethylene glycol to be used to establish the relative degree of solvent exposure of protein phenylalanine. PMID- 1897991 TI - Purification and characterization of pregnant sheep myometrium myosin light chain kinase. AB - Myosin light chain kinase (MLCK) has been purified from the myometrium of pregnant sheep. The Mr of the enzyme was determined from SDS-polyacrylamide gels to be 160,000. It requires Ca2+ and calmodulin for activation, and phosphorylates the 20,000-Da light chains of myosin at a rapid rate. The specific activity for the myosin light chains from turkey gizzards and rabbit uterine muscle are 7.7 and 5.4 mumol/min/mg, respectively. The Km for the former substrate is 40 microM and the Vmax of the reaction is 19 mumol/min/mg. Polyclonal antibodies raised against the enzyme cross-reacted with pregnant sheep myometrium (psm), turkey gizzard (tg), and chicken gizzard MLCK. Affinity purification of the antibodies on tg-MLCK Sepharose resulted in the preparation of two fractions of antibodies with different reactivity toward these proteins. Fraction A antibodies which did not bind to the affinity column cross-reacted only with psm-MLCK while Fraction B antibodies which bound to the column cross-reacted with all three proteins. Western blots of extracts of turkey gizzards, human myometrium, and various tissues from sheep showed cross-reactivity of both fractions of antibodies with a 160,000-Da protein in the extracts of sheep smooth muscles. Only Fraction B antibodies cross-reacted with a protein (130,000 Da) in turkey gizzards and human myometrium extracts. Prolonged tryptic digestion of psm-MLCK produced large fragments Mr approximately 60,000 which appears to be similar to that formed from tg-MLCK, and some smaller peptides. Fraction A antibodies cross-reacted with the small peptides while Fraction B antibodies cross-reacted with the large fragments but not vice versa. Further analysis of the tryptic peptides suggests that the epitopes of Fraction A antibodies are localized in a peptide which appears to be in the NH2-terminal region of the molecule. PMID- 1897993 TI - Conformational stability of Cu,Zn-superoxide dismutase, the apoprotein, and its zinc-substituted derivatives: second-derivative spectroscopy of phenylalanine and tyrosine residues. AB - The relative stabilities of bovine copper-zinc superoxide dismutase (SOD), its apoprotein form, and zinc-substituted derivatives were investigated by denaturation in guanidine-HCl solutions. Analysis of the kinetics of changes in the second-derivative spectral bands of both phenylalanine and tyrosine residues was simultaneously performed. It was found that reduction of the cupric site increases the stability of the enzyme. The apoprotein appears to be the least stable form, while addition of zinc ions not only increases stability, but appears to induce a native-like conformation from a disordered form at pH 3.8. By perturbing the solvent with up to 20% ethylene glycol, at pH 6.8, it was determined that the only tyrosyl side chain appears to be about 50% solvent exposed in the apoprotein, 65% exposed in the zinc derivative, and 75% exposed in the native copper-zinc form. In contrast, all four phenylalanine residues appear to be fully buried in all of these species in the mid-pH range. At pH 2.5, as the apoprotein unfolds, the apparent solvent-exposure of the tyrosyl side chain approaches 100%, while the phenylalanyl side chains become only 70% exposed. Substantial differences in the unfolding rate constants of tyrosine and phenylalanine residues of native and zinc-substituted SOD, but not the apoprotein, suggest the presence of metal-stabilized unfolding intermediates. Unfolding as monitored by the exposure of phenylalanine residues follows first order kinetics, indicating that Phe 48 located at the interface between the two subunits is being exposed to the solvent simultaneously with the remaining three phenylalanine residues buried in the protein core. PMID- 1897994 TI - Activation of the microsomal glutathione S-transferase by metabolites of alpha methyldopa. AB - Rat liver microsomes contain a membrane-bound GSH S-transferase (GSH-tr), an enzyme that is involved in the detoxication of xenobiotics. Also located on rat liver microsomes is the cytochrome P450 system, an enzyme complex that catalyzes the conversion of several xenobiotics into reactive intermediates. In this study, it was demonstrated that reactive products from alpha-methyldopa formed by the cytochrome P450 system are able to stimulate microsomal GSH-tr. Also, products formed from alpha-methyldopa that are generated by H2O2-horseradish peroxidase and tyrosinase are able to stimulate the activity of microsomal GSH-tr. GSH was able to prevent the activation of microsomal GSH-tr. Our results indicate that the ortho-quinone or semi-ortho-quinone radical of alpha-methyldopa is responsible for the stimulation of microsomal GSH-tr, probably via arylation of the free sulfhydryl group of microsomal GSH-tr. This conclusion was supported by the observation that 4-methyl-ortho-quinone itself was able to stimulate microsomal GSH-tr via sulfhydryl arylation. Our results are in conformity with the hypothesis that reactive products formed by the cytochrome P450 complex are able to stimulate microsomal GSH-tr and possibly in this way enhance their detoxication. PMID- 1897995 TI - Kinetic studies of L-aspartase from Escherichia coli: pH-dependent activity changes. AB - The pH dependence of the kinetic parameters of the L-aspartase-catalyzed reaction have been examined in both the amination and the deamination directions. The enzyme isolated from Escherichia coli exists in a pH-dependent equilibrium between a higher pH form that has an absolute requirement for a divalent metal ion and for substrate activation, and a low pH form that does not require activation by either substrate or metal ions. The interconversion between these enzyme forms is observed near neutral pH in the profiles examined for the reaction in either direction. This pH-dependent activation has not been observed for other bacterial aspartases. Loss of activity is observed at high pH with a pK value of 9. The pH profiles of competitive inhibitors such as 3-nitropropionic acid and succinic acid have shown that the enzyme group responsible for this activity loss must be protonated for substrate binding at the active site. An enzymatic group has also been identified that must be protonated in the amination reaction, with a pK value near 6.5, and deprotonated in the deamination reaction. This group, tentatively assigned as a histidyl residue, fulfills the criteria for the acid-base catalyst at the active site of L-aspartase. PMID- 1897996 TI - Peroxisome proliferation and oxidative stress mediated by activated oxygen species in plant peroxisomes. AB - The existence of a relationship between clofibrate-induced peroxisome proliferation and oxidative stress mediated by activated oxygen species was studied in intact peroxisomes purified from Pisum sativum L. plants. Incubation of leaves with 1 mM clofibrate produced a remarkable increase in the peroxisomal activity of acyl-CoA oxidase and, to a lesser extent, of xanthine oxidase, whereas there was a nearly complete loss of catalase activity and a decrease in Mn-superoxide dismutase. Ultrastructural studies of intact leaves showed that clofibrate induced a five- and twofold proliferation of the peroxisomal and mitochondrial populations, respectively, in comparison with those in control leaves. Prolonged incubation with clofibrate produced considerable alterations in the ultrastructure of cells. In peroxisomal membranes, the NADH-induced generation of O2- radicals, as well as the lipid peroxidation of membranes, increased as a result of treatment of plants with clofibrate. In intact peroxisomes treated with this hypolipidemic drug, the H2O2 concentration was higher than in peroxisomes from control plants. These results demonstrate that clofibrate stimulates the production of activated oxygen species (O2- and H2O2) inside peroxisomes, as well as the lipid peroxidation of peroxisomal membranes. This effect is concomitant with a decrease of catalase and Mn-SOD activities, the main peroxisomal enzymatic defenses against H2O2 and O2-, and indicates that in the toxicity of clofibrate, at the level of peroxisomes, an oxidative stress mechanism mediated by activated oxygen species is involved. PMID- 1897997 TI - Radiolytic reduction of protein and nonprotein disulfides in the presence of formate: a chain reaction. AB - We have reported recently that the disulfide groups in bovine serum albumin can be reduced by a radiolytic chain reaction which occurs in deoxygenated solutions containing formate ions. This reaction, which involves the reduction of disulfide groups by hydrated electrons and carbon dioxide radical anions, has now been studied in greater detail and compared with an analogous reaction in small, disulfide containing molecules over a range of pH values and substrate concentrations. A two-step reaction is proposed to account for the reduction of disulfides in reactions which can have chain lengths of 20 or more. Thiols produced by the disulfide reduction are stable to the conditions of the reaction. For example, a biological assay showed that the integrity of glutathione was maintained even at radiation doses much larger than those required to achieve complete reduction of glutathione disulfide. It was found that the extent of disulfide reduction could easily be controlled by varying the radiation dose delivered to the solutions. Radiolytic reduction is a very useful way of reducing protein and low molecular weight disulfides without the use of excess quantities of reagents such as dithiothreitol. In many cases, the reaction solutions could be used directly for subsequent reactions and this may be of considerable value in modifying the structure of hormones, enzymes, membrane receptors, and other disulfide containing proteins. If ammonium formate is used, freeze drying is an effective way to remove the formate salt, should this be required. PMID- 1897998 TI - Oxidation-reduction properties of trimethylamine dehydrogenase: effect of inhibitor binding. AB - The redox potentials of trimethylamine dehydrogenase from the bacterium W3A1 have been determined by means of uv-visible spectroelectrochemistry. In the presence of the inhibitor tetramethylammonium chloride a shift of +0.2 V was observed in the midpoint redox potential for conversion of the oxidized 6-S-cysteinyl-FMN to the flavin radical form. The pH-independent value was +0.23 V vs the standard hydrogen electrode. The pH-dependent conversion of this radical to fully reduced flavin was shifted negative by 0.1 V in the presence of the inhibitor to -0.05 V at pH 7.0 and -0.15 V at pH 8.4. Tetramethylammonium chloride also caused moderate negative shifts (0.03-0.05 V) in the midpoint redox potential for the Fe4S(+2)4/Fe4S(+1)4 couple of trimethylamine dehydrogenase. The midpoint potentials are +0.06 V at pH 7.0 and +0.04 V at pH 8.4. Therefore, in the presence of tetramethylammonium chloride, electron transfer from the flavin radical to the Fe4S(+2)4 group is energetically unfavorable and trimethylamine dehydrogenase is trapped in the flavin radical state. The redox potential changes provide a thermodynamic basis for inhibition by tetramethylammonium chloride. Spectroelectrochemical titrations of trimethylamine dehydrogenase which had been inactivated by phenylhydrazine revealed heterogeneity in the redox behavior which had not been observed in other laboratories. The reason for this heterogeneity was not determined, but the midpoint redox potential for the Fe4S(+2)4/Fe4S(+1)4 couple of the main fraction of the inactivated enzyme was the same as that of active trimethylamine dehydrogenase. PMID- 1897999 TI - Characterization of an actin flow artifact that occurs during the presteady state dissociation of actosubfragment-1. AB - Models for the activation of the myosin subfragment-1 (S-1) ATPase activity by actin describe transitions that occur between kinetic intermediate states during steady state hydrolysis of ATP. These states consist of myosin-nucleotide complexes in rapid equilibrium binding with actin, but steady state measurements of actin binding during hydrolysis lead only to a weighted average of the individual binding constants involved. In the current work, in order to determine the individual binding constants involved in the activation process, we have investigated the presteady state kinetics of the dissociation of actomyosin by ATP. We find that an actin flow artifact appears to dominate the time course of dissociation, and characterization of this artifact reveals that its magnitude rises linearly (approximately) with the concentration of bound S-1. Attempts to subtract the actin flow artifact from the actoS-1 dissociation signal were not entirely successful due at least partially to the transient nature of the bound S 1 concentration in the first few milliseconds. However, further studies reveal that if the order of addition of actin, ATP, and S-1 are varied, the observed light scattering transients are essentially superimposable. One possible explanation of these data is that the binding constants for myosin-ATP and myosin ADP-Pi to actin are equal. However, it is also possible that the flow artifact is so large that further analysis is precluded. In addition, we show that the actin flow artifact has little effect on the fluorescence measurements of the phosphate burst reported previously. Therefore, the prior interpretation of the fluorescence data remains unchanged. PMID- 1898000 TI - Identification and characterization of protein kinase C-related enzymes in frog retina. AB - We isolated two types of protein kinase C-related enzymes (fPKC) in frog (Rana catesbeiana) retina. Three sequential steps of column chromatography of DEAE cellulose, butyl-Toyopearl, and hydroxylapatite were carried out and resulted in the separation of two types of distinct Ca2+/phospholipid-dependent protein kinase activities. These proteins reacted with antibodies raised against synthetic peptides based on the predicted amino acid sequences of rat protein kinase C delta or zeta subspecies, and showed molecular masses of 90 and 75 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, respectively. Immunocytochemical analysis of 90 and 75K fPKC in frog retina revealed that the 75K fPKC was localized in the outer segment of cone cells and in the microvillar projections of Muller cells. These results suggested that fPKCs play differential roles on the photosignal transduction in frog retina. PMID- 1898001 TI - Aerobically purified hydrogenase from Azotobacter vinelandii: activity, activation, and spectral properties. AB - The hydrogenase from Azotobacter vinelandii is typically purified under anaerobic conditions. In this work, the hydrogenase was purified aerobically. The yields were low (about 2%) relative to those of the anaerobic purification (about 20%). The rate of enzyme activity depended upon the history of the enzyme. The enzyme preparations were active as isolated in H2 oxidation, and isotope exchange. The activity increased during the assay to a new maximal level (turnover activation). Treatment with reductants (e.g., H2, dithionite, dithiothreitol, indigo carmine) resulted in greater activation (reductant activation). Activation of the hydrogenase was accompanied by decrease in visible light absorption (300-600 nm) with maximal decreases at 450 and 345 nm which indicated the reduction of iron sulfur clusters. The aerobically purified hydrogenase was susceptible to irreversible inactivation by cyanide. Pretreatment with acetylene did not influence activation of the hydrogenase. Once activated, the aerobically purified hydrogenase was indistinguishable from the anaerobically purified hydrogenase with respect to the catalytic properties tested. PMID- 1898002 TI - Role of aspartate-37 in determining cofactor specificity and binding in rat liver dihydropteridine reductase. AB - Full-length rat dihydropteridine reductase (DHPR) cDNAs have been combined with a prokaryotic expression vector and introduced into Escherichia coli. Transformed bacteria express dihydropteridine reductase immunoreactive proteins and demonstrate conversion of quinonoid dihydropteridines to their tetrahydro forms. Several recombinant enzymes have been purified to homogeneity and biochemical studies have been carried out comparing their properties with those exhibited by the rat liver enzyme. The optimal reaction conditions, kinetic constants, and stability are similar for the recombinant and naturally occurring enzyme. The results indicate that the nonmutant recombinant rat DHPR is an authentic replica of the natural protein and that the characteristics of DHPR activity are determined by a single gene product and do not require specific modification via the eukaryotic cell. In addition to the wild type, three specific mutagenic forms of the reductase, A-6-V, W-104-F, and D-37-I, and an additional abbreviated structure have also been formed. Each of the products exhibits reductase activity, although they show varied affinities for their cofactor, NADH, and less stability to chromatography, dialysis, and concentration than the wild-type enzyme. The N-terminal sequence contains a classic NADH binding region between amino acids 9 and 36, and Asp 37 is essential for binding the cofactor as is shown by the approximately 20-fold increase in dissociation constant for the D-37 I mutant and diminished kcat (approximately 43 s-1 compared to 156 s-1 for the wild-type enzyme). The results indicate that the DHPR cofactor binding site is similar to typical dinucleotide requiring dehydrogenases such as lactic acid and liver alcohol dehydrogenase. PMID- 1898003 TI - One-electron oxidative activation of 2-aminofluorene by horseradish peroxidase compounds I and II: spectral and kinetic studies. AB - Horseradish peroxidase (HRP) catalyzed oxidation of the model carcinogen 2 aminofluorene (2-AF) was studied by rapid scan spectral analysis and stopped flow kinetic measurements. Our rapid scan spectral analysis of the changes in the enzyme oxidation states clearly indicates that the reactions between HRP intermediate compounds and 2-AF are one-electron redox processes, thus a free radical is necessarily the primary product. The reactions were investigated at pH's ranging from 3.40 to 10.00. The pH profiles of rate constants suggested that 2-AF is reactive toward HRP only when it is in its neutral form; one acid-base group of pKa approximately 5 in HRP-I, and one of pKa approximately 8.6 in HRP-II affect the kinetics of HRP catalyzed 2-AF oxidation. The intrinsic second-order rate constants of 2-AF oxidation are (1.1 +/- 0.5) x 10(9) M-1 s-1 and (4.8 +/- 0.4) x 10(8) M-1 s-1 for HRP-I, the two values depending upon the state of protonation of HRP-I, and (1.7 +/- 0.2) x 10(8) M-1 s-1 for HRP-II. We suggest that the rate-controlling step is formation of a substrate cation radical, which is stabilized by the extensive pi-conjugation system of 2-AF. This is supported by the high reactivity of 4-aminobiphenyl, a similar compound, which does not fit the Hammett rho sigma correlations established for other substituted anilines; these other anilines react by hydrogen atom transfer. Thus the extraordinarily rapid reactions between 2-AF and HRP compounds I and II are attributed to the strong aromaticity of 2-AF. PMID- 1898004 TI - Alkane biosynthesis by decarbonylation of aldehyde catalyzed by a microsomal preparation from Botryococcus braunii. AB - The final step in the synthesis of n-hydrocarbons in an animal and a higher plant involves enzymatic decarbonylation of aldehydes to the corresponding alkanes by loss of the carbonyl carbon. Whether such a novel reaction is involved in hydrocarbon synthesis in the colonial microalga, Botryococcus braunii, which is known to produce unusually high levels (up to 32% of dry weight) of n-C27, C29, and C31 alka-dienes and -trienes, was investigated. Dithioerythritol severely inhibited the incorporation of [1-14C]acetate into these hydrocarbons with accumulation of the label in the aldehyde fraction in the B. braunii cells. Microsomal preparations of the alga synthesized alkane from fatty acid and aldehyde in the absence of O2. Conversion of fatty acid to alkane required CoA, ATP, and NADH, whereas conversion of aldehyde to alkane did not require the addition of cofactors. That the alkane synthesis involves a decarbonylation was shown by the production of CO and heptadecane from octadecanal. CO was identified by adsorption to RhCl[(C6H6)3P]3. The decarbonylase had a pH optimum at 7.0, an apparent Km of 65 microM, a Vmax of 1.36 nmol/min/mg and was inhibited by the metal chelators EDTA, O-phenanthroline and 8-hydroxyquinoline. It was stimulated nearly threefold by 2 mM ascorbate and inhibited by the presence of O2. A partial (28%) retention of the aldehydic hydrogen of [1-3H]octadecanal in the heptadecane was observed; the remaining 3H was lost to H2O. The microsomal preparation also catalyzed the oxidation of 14CO to 14CO2, with a pH optimum of 7.0. This accounts for the nonstoichiometry of CO to heptadecane observed. In vivo studies with 14CO showed that the label was incorporated into metabolic products. This metabolic conversion of CO, not found in the previously examined hydrocarbon synthesizing systems, may be necessary for organisms that produce large amounts of hydrocarbons such as the present alga. The mechanism of the decarbonylation and the nature of the decarbonylase remain to be elucidated. PMID- 1898005 TI - Structural and functional effects of mutations altering the subunit interface of mitochondrial malate dehydrogenase. AB - Among highly conserved residues in eucaryotic mitochondrial malate dehydrogenases are those with roles in maintaining the interactions between identical monomeric subunits that form the dimeric enzymes. The contributions of two of these residues, Asp-43 and His-46, to structural stability and catalytic function were investigated by construction of mutant enzymes containing Asn-43 and Leu-46 substitutions using in vitro mutagenesis of the Saccharomyces cerevisiae gene (MDH1) encoding mitochondrial malate dehydrogenase. The mutant enzymes were expressed in and purified from a yeast strain containing a disruption of the chromosomal MDH1 locus. The enzyme containing the H46L substitution, as compared to the wild type enzyme, exhibits a dramatic shift in the pH profile for catalysis toward an optimum at low pH values. This shift corresponds with an increased stability of the dimeric form of the mutant enzyme, suggesting that His 46 may be the residue responsible for the previously described pH-dependent dissociation of mitochondrial malate dehydrogenase. The D43N substitution results in a mutant enzyme that is essentially inactive in in vitro assays and that tends to aggregate at pH 7.5, the optimal pH for catalysis for the dimeric wild type enzyme. PMID- 1898006 TI - Peroxidase-catalyzed bromination of tyrosine, thyroglobulin, and bovine serum albumin: comparison of thyroid peroxidase and lactoperoxidase. AB - A recent paper (Buchberger, W., 1988, J. Chromatogr. 432, 57) on lactoperoxidase catalyzed bromination of tyrosine and thyroglobulin stated, without evidence, that thyroid peroxidase (TPO) is able to use bromide as a substrate. This was in disagreement with unpublished experiments previously performed in this laboratory, and we undertook, therefore, to examine this subject further. Highly purified porcine TPO was compared with lactoperoxidase (LPO) and chloroperoxidase (CPO) for ability to catalyze bromination of tyrosine, thyroglobulin, and bovine serum albumin (BSA). The incubation mixture contained 50-100 nM peroxidase, 10 500 microM 82Br-, tyrosine (150 microM), thyroglobulin (0.3 or 1 microM), or BSA (7.5 microM), and a source of H2O2. The latter was either generated by glucose (1 mg/ml)-glucose oxidase (0.5 or 1 micrograms/ml), or added initially as a bolus (100 microM). With TPO, formation of organically bound 82Br was undetectable under all conditions in the pH range 5.4-7.0. Lactoperoxidase and CPO, on the other hand, displayed considerable brominating activity. Lactoperoxidase was much more active at pH 5.4 than at pH 7.0 and was more active with BSA as acceptor than with tyrosine or thyroglobulin. The distribution of 82Br among the various amino acids in LPO-brominated thyroglobulin and BSA was determined by HPLC. As expected, monobromotyrosine and dibromotyrosine together comprised the greatest part of the bound 82Br. However, a surprisingly high percentage (20-25%) was present as monobromohistidine. Evidence was also obtained for the presence of a small percentage of the bound 82Br as tetrabromothyronine. Peroxidase-catalyzed bromination probably depends on the oxidation of Br- to Br+ by the Compound I form of the enzyme. Since oxidation of Br- to Br+ requires a stronger oxidant than oxidation of I- to I+, our results suggest that Compound I of LPO and of CPO has a higher oxidation potential than Compound I of TPO. In vivo experiments with rats on a low iodine diet injected with 82Br- showed that even under conditions of high stimulation by thyrotropic hormone, there is negligible formation of organic bromine in the thyroid. Measurements of thyroid:serum concentration ratios for 82Br- in similar rats provided no evidence that Br- is a substrate for the iodide transport system of the thyroid. PMID- 1898007 TI - Solubility of retinoids in water. AB - Spectrophotometric and radioactive techniques were used to measure the water solubility of retinaldehyde, retinol (vitamin A), and retinoic acid under physiological conditions. Hydration decreases the molar extinction coefficient of these substances and shifts their absorption peak bathochromically (10 nm for retinal and approximately 1 nm for the rest). We find their solubility to be about 0.1 microM at room temperature, pH 7.3 (with experimental values being 0.11 microM for retinaldehyde, 0.06 microM for retinol, and 0.21 microM for retinoic acid). To prevent oxidative degradation of retinol, which is the most labile retinoid, our argon-saturated buffer solutions contained physiological levels of ascorbate or alpha-tocopherol. To the best of our knowledge, water solubility of these compounds has not yet been previously reported. Although the measured solubilities are relatively low, they are significant and may account for the movement of retinoids through the aqueous phase as observed by others during exchange with binding proteins and during intervesicular transfer in the absence of binding proteins. Diffusion of uncomplexed retinoids through the aqueous phase can be a major pathway for transport over subcellular distances. PMID- 1898008 TI - The effect of insulin supplementation on diabetes-induced alterations in the extractable levels of functional mitochondrial anion transport proteins. AB - The effect of insulin supplementation on diabetes-induced alterations in the levels of functional mitochondrial anion transport proteins has been determined. The experimental approach consisted of the extraction of the pyruvate, dicarboxylate, and citrate transport proteins from the mitochondrial inner membrane with Triton X-114 using rat liver mitoplasts (prepared from control, diabetic, or insulin-supplemented diabetic animals) as the starting material, followed by the reconstitution of the function of each transporter in a proteoliposomal system. This experimental strategy permitted the quantification of the functional levels of these three transporters in the absence of the complications that arise when such measurements are carried out with intact mitochondria (or mitoplasts). We found that treatment of diabetic rats (i.e., animals that were injected with streptozotocin 3 weeks earlier) on a daily basis with insulin for 3 weeks resulted in a reversal of the diabetes-induced (a) increase in the extractable and reconstitutable total (and specific) transport activities of the pyruvate and dicarboxylate transporters and (b) decrease in the activity of the citrate transporter. These findings indicate that diabetes induced alterations in the functional levels of mitochondrial anion transport proteins are a direct consequence of the insulin insufficiency that characterizes this disease. Furthermore, this study provides the first demonstration that insulin participates in the regulation of the functional levels of liver mitochondrial anion transport proteins. PMID- 1898009 TI - ATP-dependent DNA aggregation is a novel function of rat serum albumin. AB - An ATP-dependent DNA aggregating activity was purified from rat liver by DEAE cellulose, phosphocellulose, and novobiocin-Sepharose column chromatography. The protein aggregated superhelical, relaxed, single-, or double-stranded DNA in a divalent cation- and ATP-dependent reaction. The DNA aggregating activity was detected by retardation of a DNA-protein complex at the origin on a 1% agarose gel. The protein appeared to exist in solution as a monomer of molecular weight 66,000, and had no DNA polymerase, topoisomerase, recombinase, or ligase activity. The DNA aggregating activity was inhibited by 10 mM nalidixic acid or 1 mM novobiocin but not by 20 mM N-ethylmaleimide or camptothecin. Adenylyl(beta,gamma-methylene)-diphosphonate, adenylyl-imidodiphosphate, or adenosine-5'-O(3-thiotriphosphate) did not substitute for ATP whereas CTP, dTTP, or the ATP analog adenylyl(alpha,beta-methylene)-diphosphonate could replace ATP. The aggregated DNA was only partially dissociated by restriction endonuclease digestion but was completely dissociated by deproteinization with SDS, proteinase K, or chloroform/octanol extraction. On the basis of the molecular weight, thermostability, antigenic property, and amino acid sequence homology in the first 12 positions, we conclude that the rat liver protein is serum albumin and that the ATP-dependent DNA aggregation is a novel function of rat serum albumin. PMID- 1898010 TI - Purification and characterization of S-adenosyl-L-methionine: caffeic acid 3-O methyltransferase from suspension cultures of alfalfa (Medicago sativa L.). AB - Caffeic acid O-methyltransferase (COMT) is one of a group of proteins present in alfalfa cell cultures which can be photoaffinity labeled with S-adenosyl-L [methyl-3H]methionine. The enzyme was purified to homogeneity from elicitor treated suspension cultures and shown to exist as an active monomer of subunit Mr 41,000. COMT could be separated into two forms on the basis of their isoelectric points and relative affinities for S-adenosyl-methionine and S adenosylhomocysteine. Both forms had equal affinities for caffeic acid, were highly specific for the 3-hydroxyl group of substituted cinnamic acids, and exhibited negligible activity toward flavonoid substrates. An antiserum raised against COMT from aspen immunoprecipitated alfalfa COMT activity. Peptide mapping studies indicated that the two forms of COMT and an isoflavone O methyltransferase from alfalfa are closely related proteins. The extractable activity of COMT doubled over a 48-h period following exposure of alfalfa cell suspensions to a yeast elicitor preparation, and this was associated with a small change in the relative proportions of the two forms of the enzyme. PMID- 1898012 TI - Oxidation of methoxybenzenes by manganese peroxidase and by Mn3+. AB - Manganese peroxidase, produced by some white-rot fungi during lignin degradation, catalyzes the oxidation of Mn2+ to Mn3+. Whereas Mn3+ is known to oxidize phenolic compounds, its role in lignin degradation is not clear. We have used a series of methoxybenzenes with E1/2 values of 1.76-0.81 V (vs saturated calomel electrode) to investigate the oxidizing ability of Mn3+ chelates generated chemically and enzymatically. Although lignin peroxidase has been shown to oxidize high potential congeners, our results show that manganese peroxidase, or physiological concentrations of Mn3+, oxidize only the lower potential congeners. In addition, Mn3+ increased the rate of decay of the cation radical of 1,2,4,5 tetramethoxybenzene. The kinetics of decay continued to be first order, so Mn3+ does not oxidize the cation radical itself, but probably oxidizes a neutral dienyl radical derived from the cation radical. This indicates a possible role for Mn3+ in lignin degradation, as neutral dienyl radicals are proposed to be products of lignin peroxidase action. PMID- 1898011 TI - Acetoacetate and malate effects on succinate and energy production by O2-deprived liver mitochondria supplied with 2-oxoglutarate. AB - Acetoacetate provision to Ca(2+)-loaded liver mitochondria (less than 40 micrograms-ion Ca2+ x g protein-1), supplied with 2 mM Pi and 2-oxoglutarate as substrate, was found to prevent the mitochondrial deenergization and Ca2+ release induced by either rotenone during aerobic incubations or by O2 deprivation. Under the latter condition, the acetoacetate-promoted Ca2+ retention was entirely supported by ATP produced anaerobically at the succinylthiokinase step of the tricarboxylic acid cycle and was therefore abolished by addition of oligomycin. Surprisingly, oligomycin was also found to trigger Ca2+ release in rotenone inhibited mitochondria in the presence of acetoacetate under aerobic conditions, unless a Pi acceptor was supplied. ADP deprivation at the succinylthiokinase step is likely to be involved. As estimated from rates of succinate production in O2 deprived mitochondria or from respiration rates in rotenone-inhibited mitochondria at supramaximal acetoacetate concentrations (above 1.2 mM) in the presence of a Pi acceptor, ATP production by substrate-level phosphorylation was close to 10 mumol.g protein-1.min-1 and appeared to be limited by rates of ketone body transport across the inner membrane. The rates of anaerobic energy production obtained by coupling 2-oxoglutarate oxidation to acetoacetate reduction were markedly higher than those obtained by reactions involved in the anaerobic metabolism of amino acids, simulated by providing 2-oxoglutarate and malate to mitochondria. Energy production was limited by rates of oxidant equivalent generation under the latter condition. Our data suggest that acetoacetate could effectively contribute to sustaining anaerobic energy production from endogenous substrates in liver tissue. PMID- 1898013 TI - Inhibition of a plant sesquiterpene cyclase by mevinolin. AB - The specificity of mevinolin as an inhibitor of sterol and sesquiterpene metabolism in tobacco cell suspension cultures was examined. Exogenous mevinolin inhibited [14C]acetate, but not [3H]mevalonate incorporation into free sterols. In contrast, mevinolin inhibited the incorporation of both [14C]acetate and [3H]mevalonate into capsidiol, an extracellular sesquiterpene. Microsomal 3 hydroxy-3-methylglutaryl Coenzyme A reductase was inhibited greater than 90% by microM mevinolin, while squalene synthetase was insensitive to even 600 microM mevinolin. Sesquiterpene cyclase, the first branch point enzyme specific for sesquiterpene biosynthesis, was inhibited in a dose-dependent manner by mevinolin with a 50% reduction in activity at 100 microM. Kinetic analysis indicated that the mechanism for inhibition was complex with mevinolin acting as both a competitive and noncompetitive inhibitor. The results suggest that the mevinolin inhibition of [3H]mevalonate incorporation into extracellular sesquiterpenes can, in part, be attributed to a secondary, but specific, site of inhibition, the sesquiterpene cyclase. PMID- 1898015 TI - Substrate access channel geometry of soluble and membrane-bound cytochromes P450 as studied by interactions with type II substrate analogues. AB - The problems of alterations in the tertiary structure at the cytochrome P450 active site after isolation from the microsomal membrane and comparative analysis of the structures of the active sites of membrane-bound P450 and soluble P450cam have been studied in terms of using bifunctional compounds (I-IV). These amphiphilic compounds contain a pyridine radical, an aliphatic chain of variable length (n), and diphosphonic acid at the end of the molecule. There exists an optimal length (n) at which the interaction between I-IV and P450 is rather efficient. Comparison of the data on such interactions with microsomal P450, as well as P450 isolated from the membrane in oligomeric and monomeric states, and P450cam allows the estimation of the distance between the Fe3+ ion in the active site and the charged residues (Lys/Arg) on the enzyme surface (approximately 17 A for all P450s). PMID- 1898014 TI - Affinity purification and characterization of 2,4-dichlorophenol hydroxylase from Pseudomonas cepacia. AB - 2,4-Dichlorophenol hydroxylase, a flavoprotein monooxygenase from Pseudomonas cepacia grown on 2,4-dichlorophenoxyacetic acid (2,4-D) as the sole source of carbon, was purified to homogeneity by a single-step affinity chromatography on 2,4-DCP-Sepharose CL-4B. The enzyme was eluted from the affinity matrix with the substrate 2,4-dichlorophenol. The enzyme has a molecular weight of 275,000 consisting of four identical subunits of molecular weight 69,000 and requires exogenous addition of FAD for its complete catalytic activity. The enzyme required an external electron donor NADPH for hydroxylation of 2,4-dichlorophenol to 3,5-dichlorocatechol. NADPH was preferred over NADH. The enzyme had Km value of 14 microM for 2,4-dichlorophenol, and 100 microM for NADPH. The enzyme activity was significantly inhibited by heavy metal ions like Hg2+ and Zn2+ and showed marked inhibition with thiol reagents. Trichlorophenols inhibited the enzyme competitively. The hydroxylase activity decreased as a function of increasing concentrations of Cibacron blue and Procion red dyes. The apoenzyme prepared showed complete loss of FAD when monitored spectrophotometrically and had no enzymatic activity. The inactive apoenzyme was reconstituted with exogenous FAD which completely restored the enzyme activity. PMID- 1898016 TI - Kifunensine inhibits glycoprotein processing and the function of the modified LDL receptor in endothelial cells. AB - Kifunensine is an alkaloid that is produced by the actinomycete Kitasatosporia kifunense and resembles the cyclic oxamide derivative of 1 aminodeoxymannojirimycin in structure. We previously showed that this compound was a potent inhibitor of the purified glycoprotein processing enzyme, mannosidase I, and caused an almost complete inhibition in the formation of complex types of oligosaccharides with the concurrent accumulation of N-linked oligosaccharides having Man9(GlcNAc)2 structures in influenza virus-infected Madin Darby canine kidney cells. Kifunensine, at concentrations of 1 microgram/ml or higher in the culture medium, caused an almost complete inhibition in the formation of complex types of oligosaccharides by human skin fibroblasts or aortic endothelial cells, with the resulting accumulation of Man9(GlcNAc)2 oligosaccharides on the cell surface N-linked glycoproteins, and more specifically on the scavenger-LDL receptor. When endothelial cells were grown in the presence of 1 microgram/ml of kifunensine, there was a 75% inhibition in the ability of these cells to degrade 125I-labeled acetyl-LDL, but this inhibitor appeared to have little or no effect on the ability of either endothelial cells or fibroblasts to degrade 125I-labeled LDL, even at kifunensine concentrations of 10 micrograms/ml. Kifunensine also decreased the binding of the labeled acetyl LDL by the scavenger receptor of the endothelial cells, but the amount of this inhibition relative to controls was significantly less than that of the degradation, suggesting that kifunensine affects two different steps of acetyl LDL metabolism in these cells. Endothelial cells grown in the presence of 10 micrograms/ml of kifunensine had only half the activity of the lysosomal enzymes, beta-hexosaminidase, and proteases, as did control cells, although kifunensine did not affect [3H]leucine incorporation into protein. Thus, kifunensine apparently affects the activity of (some) lysosomal enzymes in an as yet undefined manner. PMID- 1898017 TI - A calcium-binding protein from rabbit lung cytosol identified as the product of growth-regulated gene (2A9) and its binding proteins. AB - Using Ca(2+)-dependent affinity chromatography on a synthetic compound (W-77) coupled Sepharose 4B column, we purified two different Ca(2+)-binding proteins from rabbit lung extracts. The molecular weights of these proteins were estimated to be 17 kDa (calmodulin) and 10 kDa, respectively. The partial amino acid sequence of the 10-kDa protein revealed that it has two EF-hand structures. In addition, the 10-kDa protein was highly homologous (91%) to the product of growth regulated gene, 2A9 (calcyclin). The Ca(2+)-binding property of the 10-kDa protein was observed by a change in the uv difference spectrum. Equilibrium dialysis showed that 1 mol of the 10-kDa protein bound to 2.04 +/- 0.05 mol of Ca2+ in the presence of 10(-4) M Ca2+. However, the protein failed to activate calmodulin-dependent enzymes such as Ca2+/CaM kinase II, myosin light chain kinase, and phosphodiesterase. We found that a 50-kDa cytosolic protein of the rabbit lung, intestine, and spleen bound to the 10-kDa protein, in a Ca(2+) dependent manner. The distribution of calcyclin and calcyclin binding proteins was unique and seems to differ from that of calmodulin and calmodulin-binding proteins. Thus, calcyclin probably plays a physiological role through its binding proteins for the Ca(2+)-dependent cellular response. PMID- 1898018 TI - Glucosamine-6-phosphate synthase from Escherichia coli yields two proteins upon limited proteolysis: identification of the glutamine amidohydrolase and 2R ketose/aldose isomerase-bearing domains based on their biochemical properties. AB - The proteolysis of native glucosamine-6-phosphate synthase (Mr 67,000) from Escherichia coli was investigated using two nonspecific and five specific endoproteinases, alpha-chymotrypsin generated two nonoverlapping polypeptides CT1 and CT2 of Mr 40,000 and 27,000 lacking glucosamine-6P synthesizing activity. Amino terminal and carboxy terminal sequence analysis showed that cleavage occurred between positions 240 and 241 of the primary sequence without further degradation. The glutamine amidohydrolase activity was located in the CT2 N terminal polypeptide which was capable of incorporating 0.7 equivalent of the glutamine site-directed affinity label [2-3H]-N3-(4-methoxyfumaroyl) diaminopropionic acid indicating that it bears the amidotransferase function. CT1 which displayed a higher reactivity than CT2 for fructose-6P binding contains the ketose/aldose isomerase activity. These data suggest the existence of a hinge structure essential for the catalytically efficient coupling between the ammonia generating domain and the sugar binding domain and support the model recently proposed by Mei and Zalkin in which purF-type amidotransferases contain a glutamine hydrolase domain of approximately 200 amino acids fused to an ammonia transfer domain. PMID- 1898019 TI - The synthesis and characterization of uridine 5'-(beta-L-rhamnopyranosyl diphosphate) and its role in the enzymic synthesis of rutin. AB - Uridine 5'-(beta-L-rhamnopyranosyl diphosphate) was synthesized by the condensation of uridine 5'-diphenylpyrophosphate and beta-L-rhamnopyranosyl phosphate. That sugar 1-phosphate was made via the phosphitylation of the hemiacetal hydroxyl group of 2,3,4-tetra-O-acetyl-beta-L-rhamnopyranose. An enzyme preparation from the primary leaves of mung bean (Phaseolus aureus) was shown to catalyze the transfer of L-rhamnose from UDP-beta-L-rhamnose to the flavonol D-glucoside isoquercitrin to form rutin. PMID- 1898020 TI - Continuous measurement of mitochondrial pH gradients in isolated hepatocytes by difference ratio spectroscopy. AB - The pH gradient, delta pH, present across the inner mitochondrial membrane in isolated rat hepatocytes was continuously monitored with a novel spectroscopic technique that utilizes the weak acid fluorescein. Unlike most cytosolic pH indicators, such as 2',7'-bis(carboxyethyl)-5,(6)-carboxyfluorescein (BCECF), fluorescein freely distributes between the cytosolic and mitochondrial compartments. As is typical for weak acids, the distribution between these two compartments is governed by the magnitude of the pH gradient. Since fluorescein has two ionizable groups, the fluorescein dianion is concentrated in the mitochondrial compartment 100-fold per delta pH unit. In this compartment, fluorescein absorbance (or excitation) spectra are red-shifted about 6-8 nm in the matrix environment, as compared to the cytosolic dye at equivalent pH values. The combination of favorable mitochondrial accumulation and red-shifted spectra enables mitochondrial pH to be continuously monitored qualitatively in whole cells by dual wavelength spectroscopy (510 minus 540 nm). When the cytosolic pH is determined by independent means, the mitochondrial pH can be quantitated, based on the theoretical dependence of the fluorescein distribution ratio on delta pH, the ratio of cytosolic to mitochondrial volumes, and the known extinction coefficients for the dye in the cytosolic and mitochondrial compartments. The sensitivity of the method for following kinetic responses in mitochondrial pH is especially noteworthy; a 0.1-unit change in delta pH is easily distinguished, with a time resolution of less than a second. PMID- 1898021 TI - Oxygen-radical-mediated lipid peroxidation and inhibition of ADP-induced platelet aggregation. AB - The effects of lipid peroxidation on ADP-induced aggregation of washed rat platelets were examined using a oxygen-radical-generating system consisting of H2O2 and ferrous ion. Lipid peroxidation was assessed by measurement of thiobarbituric acid-reactive substances (TBARS). Incubation of the platelets with various concentrations of H2O2 (2-10 mM) in the presence of 10 microM Fe2+ resulted in a decrease of the aggregating capacity and an increase of TBARS value, depending on the concentrations of H2O2. Addition of catalase (0.1 mg/ml) to the incubation medium containing 10 microM Fe2+ and 10 mM H2O2 effectively protected the aggregating capacity, but superoxide dismutase (0.1 mg/ml) did not protect H2O2/Fe(2+)-induced inhibition of the platelet aggregation. The results of kinetic studies on the platelet aggregation with varying ADP and Ca2+ concentrations suggested that treatment of the platelets with H2O2/Fe2+ causes decreases in the binding affinities of ADP and Ca2+ for the platelets. On the basis of these results, change in the aggregating capacity of the platelets by treatment with H2O2/Fe2+ is discussed in relation to lipid peroxidation. PMID- 1898022 TI - Purification and immunocharacterization of a plant cytochrome P450: the cinnamic acid 4-hydroxylase. AB - Cinnamic acid 4-hydroxylase (CA4H) was purified from microsomes of manganese induced Jerusalem artichoke (Helianthus tuberosus L.) tuber tissues. The three step purification procedure involved solubilization and phase partitioning in Triton X-114, followed by chromatography on DEAE-Trisacryl and hydroxylapatite columns. Purification was monitored using carbon monoxide and type I substrate binding properties of the enzyme. The protein, purified to electrophoretic homogeneity, showed an Mr of about 57,000 on SDS-PAGE. Polyclonal antibodies raised against this protein selectively reacted with a 57-kDa polypeptide on Western blots of induced Jerusalem artichoke microsomes. The antibody selectively and strongly inhibited CA4H activity from several plant species. PMID- 1898023 TI - Inhibition of glutathione disulfide reductase by glutathione. AB - Rat-liver glutathione disulfide reductase is significantly inhibited by physiological concentrations of the product, glutathione. GSH is a noncompetitive inhibitor against GSSG and an uncompetitive inhibitor against NADPH at saturating concentrations of the fixed substrate. In both cases, the inhibition by GSH is parabolic, consistent with the requirement for 2 eq. of GSH in the reverse reaction. The inhibition of GSSG reduction by physiological levels of the product, GSH, would result in a significantly more oxidizing intracellular environment than would be realized in the absence of inhibition. Considering inhibition by the high intracellular concentration of GSH, the steady-state concentration of GSSG required to maintain a basal glutathione peroxidase flux of 300 nmol/min/g in rat liver is estimated at 8-9 microM, about 1000-fold higher than the concentration of GSSG predicted from the equilibrium constant for glutathione reductase. The kinetic properties of glutathione reductase also provide a rationale for the increased glutathione (GSSG) efflux observed when cells are exposed to oxidative stress. The resulting decrease in intracellular GSH relieves the noncompetitive inhibition of glutathione reductase and results in an increased capacity (Vmax) and decreased Km for GSSG. PMID- 1898024 TI - Novel stereoselectivity of rat liver cytochrome(s) P450 toward enantiomers of the trans-1,2-dihydrodiol of triphenylene. AB - Metabolism of 3H-labeled (+)-(S,S)- and (-)-(R,R)-1,2-dihydrodiols of triphenylene by rat liver microsomes and 11 purified isozymes of cytochrome P450 in a reconstituted monooxygenase system has been examined. Although both enantiomers were metabolized at comparable rates, the distribution of metabolites between phenolic dihydrodiols and bay-region, 1,2-diol 3,4-epoxide diastereomers varied substantially with the different systems. Treatment of rats with phenobarbital (PB) or 3-methylcholanthrene (MC) caused a slight reduction or less than a twofold increase, respectively, in the rate of total metabolism (per nanomole of cytochrome P450) of the enantiomeric dihydrodiols compared to microsomes from control rats. Among the 11 isozymes of cytochrome P450 tested, only cytochromes P450c (P450IA1) and P450d (P450IA2) had significant catalytic activity. With either enantiomer of triphenylene 1,2-dihydrodiol, both purified cytochrome P450c (P450IA1) and liver microsomes from MC-treated rats formed diol epoxides and phenolic dihydrodiols in approximately equal amounts. Purifed cytochrome P450d (P450IA2), however, formed bay-region diol epoxides and phenolic dihydrodiols in an 80:20 ratio. Interestingly, liver microsomes from control or PB-treated rats produced only diol epoxides and little or no phenolic dihydrodiols. The diol epoxide diastereomers differ in that the epoxide oxygen is either cis (diol epoxide-1) or trans (diol epoxide-2) to the benzylic 1-hydroxyl group. With either purified cytochromes P450 (isozymes c or d) or liver microsomes from MC-treated rats, diol epoxide-2 is favored over diol epoxide-1 by at least 4:1 when the (-)-enantiomer is the substrate, while diol epoxide-1 is favored by at least 5:1 when the (+)- enantiomer is the substrate. In contrast, with liver microsomes from control or PB-treated rats, formation of diol epoxide 1 relative to diol epoxide-2 was favored by at least 2:1 regardless of the substrate enantiomer metabolized. This is the first instance where the ratio of diol epoxide-1/diol epoxide-2 metabolites is independent of the dihydrodiol enantiomer metabolized. Experiments with antibodies indicate that a large percentage of the metabolism by microsomes from control and PB-treated rats is catalyzed by cytochrome P450p (P450IIIA1), resulting in the altered stereoselectivity of these microsomes compared to that of the liver microsomes from MC-treated rats. PMID- 1898025 TI - Mechanism of monoclonal antibody inhibition/stimulation of reactions catalyzed by cytochrome P450IIB1. AB - We describe two monoclonal antibodies (MAbs) against rat cytochrome P450IIB1 and investigate the mechanisms by which they influence P450IIB1-mediated catalysis. MAb ce9 partially inhibits the activities toward p-nitroanisole, 7 ethoxycoumarin, and benzphetamine as well as NADPH oxidation. These findings can be explained by the observation that ce9 cross-links P450 to form large aggregates resulting in the inhibition of the functional interaction with NADPH cytochrome P450 reductase. Binding of ce9 to P450IIB1 does not affect the spin state of the P450 heme, as revealed by comparing the magnetic circular dichroism (MCD) spectra of free and antibody-bound P450IIB1. On the other hand, the second antibody tested, MAb 14E10, induces a remarkable low to high spin transition upon binding to P450IIB1, as shown by MCD difference spectroscopy. This MAb stimulates activities toward p-nitroanisole and 7-ethoxycoumarin without affecting the rate of NADPH oxidation. This observation indicates that MAb 14E10 may increase the efficiency of electron utilization by P450IIB1. Benzphetamine metabolism remains unchanged in the presence of MAb 14E10. PMID- 1898026 TI - Target enzymes on hepatic dysfunction caused by dietary products of lipid peroxidation. AB - Dietary products of lipid peroxidation cause hepatic dysfunction due to decreases in the activities of some hepatic enzymes and to depletion of CoA. An idea about the decreases and depletion is that the enzymes and CoA could be injured directly by the incorporated products in the liver. Their inactivations in vitro were then examined using a reasonable amount of peroxidation products. The hepatic cytosol, microsomes, and mitochondria were incubated with 10, 15, and 20 micrograms/mg protein of peroxidation products, respectively, and changes in the enzymatic activities were monitored. Glucose-6-phosphate dehydrogenase, mitochondrial NAD dependent aldehyde dehydrogenase, glucokinase, and glyceradehyde phosphate dehydrogenase were inactivated, and the CoA level was decreased, but the other hepatic enzymes were not. Although glyceraldehyde phosphate dehydrogenase was most sensitive to peroxidation products in vitro, the decrease in activity was not detected by the oral dose of secondary products. On the other hand, among the components of peroxidation products, hydroperoxides and polymers are not incorporated in the liver, but decomposed products of low molecular weight are incorporated. Glucokinase among the above enzymes was not inactivated by the low molecular-weight products. It was therefore concluded that glucose-6-phosphate dehydrogenase, mitochondrial NAD-dependent aldehyde dehydrogenase, and CoA were targets of the direct attack by incorporated components of peroxidation products in the liver. PMID- 1898027 TI - The binding of pyridoxal 5'-phosphate to human serum albumin. AB - Most of the pyridoxal 5'-phosphate (PLP) in plasma is bound to protein, primarily albumin. Binding to protein is probably important in transporting PLP in the circulation and in regulating its metabolism. The binding of PLP to human serum albumin (HSA) was studied using absorption spectral analysis, equilibrium dialysis, and inhibition studies. The kinetics of the changes in the spectrum of PLP when mixed with an equimolar concentration of HSA at pH 7.4 followed a model for two-step consecutive binding with rate constants of 7.72 mM-1 min-1 and 0.088 min-1. The resulting PLP-HSA complex had absorption peaks at 338 and 414 nm and was reduced by potassium borohydride. The 414-nm peak is probably due to a protonated aldimine formed between PLP and HSA. The binding of PLP to bovine serum albumin (BSA) at equimolar concentrations at pH 7.4 occurred at about 10% the rate of its binding to HSA. The final PLP-BSA complex absorbed maximally at 334 nm and did not appear to be reduced with borohydride. Equilibrium dialysis of PLP and HSA indicated that there were more than one class of binding sites of HSA for PLP. There was one high affinity site with a dissociation constant of 8.7 microM and two or more other sites with dissociation constants of 90 microM or greater. PLP binding to HSA was inhibited by pyridoxal and 4-pyridoxic acid. It was not inhibited appreciably by inorganic phosphate or phosphorylated compounds. The binding of PLP to BSA was inhibited more than its binding to HSA by several compounds containing anionic groups. It is concluded that PLP binds differently to HSA than it does to BSA. PMID- 1898028 TI - Actin polymerization in cellular oxidant injury. AB - Microfilaments undergo an ATP-dependent disruption into shortened bundles following cellular exposure to oxidants. This phenomenon does not require a net change in the amount of polymerized actin. However, increased amounts of polymerized actin have been detected in oxidant-injured cells and it was the purpose of this study to determine the conditions under which the actin polymerization may occur. Utilizing the formation of oxidized glutathione (GSSG) as an indicator of cellular sulfhydryl oxidation, conditions were chosen to accentuate sulfhydryl oxidation within the target P388D1 cell line following exposure to the oxidants, H2O2 and diamide. Using the DNase I and flow cytometric assays of actin polymerization, significant polymerization of actin was detected only under conditions in which sulfhydryl oxidation occurred after exposure to the two oxidizing agents. Greater sulfhydryl oxidation early in the course of injury was associated with a greater rate and extent of actin polymerization in the injured cells. Experiments with cells depleted of glutathione (GSH) demonstrated that neither loss of GSH nor absolute levels of GSSG formed during oxidant exposure were responsible for the polymerization of actin. The data presented are consistent with the hypothesis that oxidizing conditions which induce significant sulfhydryl oxidation in target cells are correlated with assembly of polymerized actin and that this represents a process which is distinct and separate from the ATP-dependent gross disruption of microfilaments. PMID- 1898029 TI - Nonenzymatic modifications of amino sugars in vitro. AB - Browning reactions of amino sugars were observed in a variety of sterile pH buffers at 25-37 degrees C. These reactions were signaled by an increase in absorbance at 273 nm, followed by an increase in absorbance at 320-360 nm. The reactions were maximal at pH 7.0 in phosphate buffer. Acidic solutions (pH less than 2.2) of 50 mM D-glucosamine hydrochloride gave only a negligible reaction and 2-acetamido-2-deoxy-D-glucose was unreactive. Half of the D-glucosamine in a 100 mM solution in sterile 0.2 M sodium phosphate buffer, pH 7.4, at 37 degrees C decomposed or was transformed in 27 h. A comparison of reactivity in generating A273 and A340 chromophores showed D-mannosamine greater than D-galactosamine greater than D-glucosamine. Permanganate oxidation of incubated glucosamine solutions afforded a compound which chromatographed like 2,5-pyrazinedicarboxylic acid and gave the same ultraviolet absorption spectrum. This, together with fractionating and thin-layer chromatography of the products of glucosamine incubation, suggests that 2,5-bis(tetrahydroxybutyl)pyrazine is formed as one of the products of autocondensation of D-glucosamine in accord with the report of Candiano et al. (1988, Carbohydr. Res. 184, 67-75) on products formed in glucosamine-lysine incubation mixtures. Formation of products absorbing at 325 360 nm was inhibited by the chelator diethylene-triaminepentaacetic acid. This suggests that the later reactions may be mediated by a metal-stimulated free radical mechanism. After 4 days incubation high molecular weight products with absorbance maxima at 273 nm and 325-360 nm were detected. Some of these were retained by dialysis membranes of molecular weight cut-off greater than 3500 and greater than 12,000. PMID- 1898030 TI - Hematin- and peroxide-catalyzed peroxidation of phospholipid liposomes. AB - The effect of hydroperoxides on hematin-catalyzed initiation and propagation of lipid peroxidation was examined utilizing soybean phosphatidylcholine liposomes as model membranes. Polarographic and spectrophotometric methods revealed a bimodal pseudocatalytic activity for hematin. A slow initiation phase of peroxidation was observed in the presence of low peroxide concentrations, whereas a fast propagative phase was observed at higher peroxide levels. Peroxide levels were manipulated enzymatically by the combination of phospholipase A2 and lipoxidase or by the direct addition of linoleic acid hydroperoxide, cumene hydroperoxide, or hydrogen peroxide. In addition, the effect of two different techniques for liposome preparation, i.e., sonication and extrusion, were compared on the basis of peroxidation kinetics. High pressure liquid chromatography analysis showed that sonicated liposomes contained higher levels of endogenous peroxides than the extruded ones. These sonicated liposomes also exhibited more rapid peroxidation following hematin addition. Extruded liposomes were more resistant to hematin-catalyzed peroxidation but became better substrates when exogenous hydroperoxides were added. All three peroxides reacted with hematin during which decomposition of peroxide and irreversible oxidation of hematin took place. Spectral analysis of hematin indicated that a higher oxidation state of hematin iron may be transiently formed during reaction with hydroperoxides and accounts for the propagation of lipid peroxidation when reactions proceed in the presence of soybean phosphatidylcholine liposomes. Of the three peroxides studied, linoleic acid hydroperoxide was most efficient in supporting hematin-catalyzed lipid peroxidation. The relevance of our findings is discussed in terms of the concentration dependence for lipid peroxides in determining the rate and extent of radical propagation chain reactions catalyzed by heme-iron catalysts such as hematin. Variation of hematin and linoleic hydroperoxide concentrations may provide an efficient and reproducible method for inducing and manipulating the rates and extent of lipid peroxidation through facilitation of the propagative phase of lipid peroxidation. In addition, we address a problem inherent to in vitro studies of heme-catalyzed lipid peroxidation where preparations of peroxide-free membranes should be of concern. PMID- 1898031 TI - The role of protein kinase C in the stimulation of phosphatidylcholine synthesis by phospholipase C. AB - The role of protein kinase C in the stimulation of phosphatidylcholine (PC) synthesis by phospholipase C was investigated. Phospholipase C treatment of Chinese hamster ovary cells (CHO) generates diacylglycerol, which is an activator of protein kinase C. The protein kinase C activator, 12-O-tetradecanoyl-phorbol 13-acetate (TPA) stimulated choline incorporation into two CHO cell lines, a wild type cell line, WTB, and a mutant cell line, DTG 1-5-4. DTG 1-5-4 is a mutant defective in receptor-mediated endocytosis. A 3-h phospholipase C treatment resulted in the activation and translocation of CTP:phosphocholine cytidylyltransferase in both cell lines. TPA treatment, however, resulted in only a slight (20%) translocation of cytidylyltransferase in WTB; no detectable translocation of cytidylyltransferase was observed in DTG 1-5-4. A decrease in the phosphocholine pools was observed in response to TPA treatment in both cell lines, which indicated that the cytidylyltransferase step was being activated. Phospholipase C stimulated choline incorporation into PC even when protein kinase C had been down-regulated in both cell lines. It was concluded that phospholipase C does not activate PC synthesis by activating protein kinase C. PMID- 1898032 TI - Purification and characterization of polyamine-stimulated protein kinase (casein kinase II) from bovine spermatozoa. AB - Casein kinase II from bovine epididymal spermatozoa was purified to apparent homogeneity by repeated chromatography with phosphocellulose and gel filtration with sephacryl S-200. The purified enzyme exhibited a molecular mass of 130 kDa by gel filtration and displayed three polypeptide bands with molecular masses of 26, 33, and 36 kDa by SDS-polyacrylamide gel electrophoresis. Antibodies raised against calf thymus casein kinase II cross reacted with the three sperm polypeptides. Incubation of the holoenzyme with either [gamma-32P]ATP or [gamma 32P]GTP resulted in the phosphorylation of the 26-kDa subunit. The enzymatic activity with casein as substrate was strongly inhibited by nanomolar heparin and greatly stimulated by micromolar spermine. With casein as substrate, the specific activity of the pure enzyme (0.5 mumol/min/mg protein) was comparable to that of casein kinase II from other sources. Endogenous substrates of the kinase were demonstrated by incubating sperm cytosolic extracts with [gamma-32P]GTP, under conditions that limit the expression of other protein kinases, and analyzing the products by SDS-PAGE and autoradiography. Similar results were obtained when sperm extracts, suitably diluted to minimize endogenous casein kinase II, were incubated with [gamma-32P]GTP and aliquots of pure sperm casein kinase II. Low concentrations (50 microM) spermine strongly enhanced the phosphorylation of 92- and 106-kDa cytosolic proteins. Our results clearly show that casein kinase II is present in spermatozoa and that it shares many of the properties of the enzyme from other sources. Further, they indicate that the enzyme plays a role in mediating the phosphorylation state of sperm proteins. PMID- 1898033 TI - Regulation of Phosphoenolpyruvate carboxylase from Crassula argentea: effect of incubation with ligands and dilution on oligomeric state, activity, and allosteric properties. AB - The relationship between the aggregation state and allosteric properties of purified phosphoenolpyruvate carboxylase from Crassula argentea was examined using both kinetic and physical techniques. Analysis by native polyacrylamide gel electrophoresis showed that dilution induced a dissociation of the active tetramer to a less active dimer. Kinetic assays showed that inhibition of phosphoenolpyruvate carboxylase by 5 mM malate measured at a saturating phosphoenolpyruvate concentration rose to nearly 80% with increasing preassay dilution while the activity in the absence of malate remained constant. Kinetic bursts were observed when enzyme-initiated assays were measured at a subsaturating phosphoenolpyruvate concentration. At saturating phosphoenolpyruvate concentrations, however, increasing lags developed in response to increasing the preassay dilution of the enzyme. Further, dynamic laser-light scattering measurements showed that preincubation of the dilute enzyme with phosphoenolpyruvate stabilized the tetramer while the presence of malate induced dimer formation. These observations confirm and extend earlier work with the extracted active malate insensitive night and less active, malate sensitive day forms of the enzyme (Wu and Wedding [1985] Plant Physiol. 77, 667 675). Activity measured at subsaturating phosphoenolpyruvate concentrations dropped with increasing preassay dilution of enzyme, while activation by 3.2 mM glucose 6-phosphate, assayed at a low phosphoenolpyruvate concentration (0.044 mM), increased with dilution to nearly 400%. In this case activation results from a decrease in the control rate as the activity measured in the presence of glucose 6-phosphate was nearly constant, similar in effect to saturating phosphoenolpyruvate in the assay. Glucose 6-phosphate induced tetramer formation of the dilute enzyme as measured by light-scattering similar to the effects induced by PEP. In addition, when diluted (dimeric) PEPC was preincubated with PEP or glucose 6-phosphate the enzyme became less sensitive to malate inhibition, while the active-site directed ligand 2-phosphoglycolate had no effect on malate inhibition. These results indicate that both the substrate PEP and the activator glucose 6-phosphate stabilize the active tetramer via binding and interaction at an activator site separate from the active site. PMID- 1898034 TI - Pyrroline-5-carboxylate reductase in soybean nodules: isolation/partial primary structure/evidence for isozymes. AB - Electrophoretic evidence was obtained for two forms of pyrroline-5-carboxylate reductase (P5CR) in soybean nodules. One form was purified over 2300-fold. The apparent sizes of the polypeptides comprising the pyrroline-5-carboxylate reductases from soybean cytosol (29,700) and Escherichia coli (28,000) were consistent with those predicted from the sequences of the genes encoding them (Deutch et al., 1982 Nucleic Acid Res. 10, 7701-7714; Delauney and Verma, 1990 Mol. Gen. Genet. 221, 299-305). Primary structural analysis of the intact soybean P5CR subunit indicated that the amino-terminal residue is blocked. Analyses of a 12-mer and a 21-mer isolated from a cyanogen bromide digest were consistent with the proposition that the soybean P5CR isolated in these studies is very similar, although perhaps not identical, to the polypeptide predicted for the recently cloned soybean reductase (Delauney and Verma, 1990 Mol. Gen. Genet. 221, 299 305). PMID- 1898035 TI - Regulation of mitochondrial K+/H+ antiport activity by hydrogen ions. AB - The effect of matrix pH (pHi) on the activity of the mitochondrial K+/H+ antiport has been studied using the fluorescence of 2,7-biscarboxyethyl-5(6) carboxyfluorescein (BCECF) to monitor pHi and passive swelling in K+ acetate to follow antiport activity. Heart mitochondria suspended in hypotonic K+ acetate in the absence of respiration show an initial delta pH of -0.4 (interior acid) that decays slowly. Addition of A23187 to deplete matrix Mg2+ results in a further acid shift in pHi followed by equilibration of delta pH. This equilibration appears to depend on K+/H+ antiport and is slow at acid pHi but very rapid when the matrix is alkaline. Swelling of Mg(2+)-depleted mitochondria in K+ acetate is multiphasic with a slow initial rate, a period of maximum swelling, and a final period in which the rate declines. At constant external pH (pH0), the initial rate of swelling is faster with increasing pHi and the time to the onset of the maximum swelling rate decreases. The maximum swelling rate is initiated at pHi 7.4 when pH0 is 7.8 and at pHi 7.1 when pH0 is 7.4. The maximum rate of swelling increases linearly with increasing pH0 in the range from 7.0 to 8.2. This rate also shows a linear relationship to the value of pHi at the time the maximum rate is attained. Dixon plots of the reciprocal of the maximum swelling rate vs [H+]0 suggest that external [H+] is a noncompetitive inhibitor of K+ entry on the antiport. It is concluded that K+/H+ antiport in Mg(2+)-depleted heart mitochondria can be regulated by matrix [H+] (see Beavis, A. D., and Garlid, K. D. (1990) J. Biol. Chem. 265, 2538-2545), but that this antiport is also sensitive to external [H+] or to delta pH when it acts in the direction of K+ uptake. PMID- 1898037 TI - Structural and functional changes associated with cyanogen bromide treatment of wheat germ agglutinin. AB - The lectin, wheat germ agglutinin (WGA), has been shown to have a significant larvicidal effect on the European corn borer, a major insect pest of corn. In order to characterize this toxic effect, we have undertaken structure-function studies on WGA. To this extent, the effect of cyanogen bromide (CNBr) on the conformation, subunit interactions, and biological activity of WGA has been investigated. The CNBr-modified lectin exhibits no toxicity to the ECB, cannot dimerize, does not bind to N-acetylglucosamine or its polymers, has no or vastly reduced hemagglutinating activity against red blood cells of different animals, and shows loss of an antigenic determinant by immunodiffusion. The CD spectrum of CNBr-WGA is not significantly different from that of native WGA, although the intrinsic fluorescence shows about 30% quenching. Our results suggest that the integrity of the N-terminal domain of WGA is essential for dimer formation. Furthermore, toxicity of WGA to ECB may be intrinsically related to its ability to dimerize and bind to sugar residues. PMID- 1898036 TI - Enhancement of heme oxygenase-1 synthesis by glutathione depletion in Chinese hamster ovary cells. AB - Chinese hamster ovary cells cultured in vitro were used to assess the role of glutathione metabolism in the induction of the 32-kDa stress protein. Enhanced synthesis of the 32-kDa protein was observed after cells were incubated with CdCl2 or diethylmaleate and protein was subjected to SDS-PAGE followed by fluorography. Concomitantly, in both cell preparations an increase in heme oxygenase activity was observed. Proteins from CdCl2- and diethylmaleate-treated cells were subjected to Western blotting and protein crossreacting with either rabbit antibody to rat liver heme oxygenase-1 (32,000 Mr) or rat testis heme oxygenase-2 (36,000 Mr) quantitated. The analysis indicated that the CdCl2 treatment increased the intensity of the HO-1 band 5.5-fold while the diethylmaleate treatment increased it three-fold relative to control. Neither treatment affected the intensity of HO-2 antibody binding. Incubation of cells with buthionine sulfoximine, under conditions which resulted in greater than or equal to 90% of the intracellular glutathione being depleted, enhanced synthesis of a 32-kDa protein when assayed by SDS-PAGE. This protein exhibited a Mr similar to the 32-kDa protein induced by either CdCl2 or diethylmaleate treatment. Proteins from buthionine sulfoximine and diethylmaleate-treated cells were mixed together and subjected to 2D PAGE. The resulting fluorograph demonstrated that both treatments produced identical patterns. In contrast, incubation of cells in diamide, a thiol oxidizing compound, resulted in enhanced synthesis of the 110-, 90-, and 73-kDa heat shock proteins but not the 32-kDa protein. The data presented have shown that depletion of glutathione by two independent methods, conjugation and inhibition of synthesis, enhances the synthesis of a 32-kDa protein identified as heme oxygenase-1; oxidation of glutathione, on the other hand did not. We interpret this to indicate that glutathione depletion rather than conjugation or oxidation represents one pathway for induction of heme oxygenase-1. PMID- 1898038 TI - Influence of anions on the activation of carbamoyl phosphate synthetase (ammonia) by acetylglutamate: implications for the activation of the enzyme in the mitochondria. AB - Rat liver carbamoyl phosphate synthetase is shown to be inhibited by anions competitively with acetylglutamate (the allosteric activator of the enzyme) with a potency decreasing in the order NO3- greater than SO4(2-) greater than Cl- approximately HCO3-. Inhibition by chloride accounts for most of the inhibition reported [Lund, P., and Wiggins, D. (1987) Biochem. J. 243, 273-276] in Tris buffer. Mes, acetate, and isethionate give little or no inhibition and phosphate inhibits noncompetitively. Plots of the KA value for acetylglutamate versus the concentration of chloride or nitrate are curved upward and binding assays demonstrate that the inhibitory anions displace acetylglutamate from the enzyme. Thus, the anions may compete with the carboxyls of acetylglutamate for positive charges at the binding site. Of the organic anions found in the mitochondrial matrix, alpha-ketoglutarate, malate, succinate, and citrate increase substantially the KA for acetylglutamate. Changes in the concentrations of ATP, HCO3-, NH4+, and Mg2+, and high concentrations of protein (60 mg/ml serum albumin) influence the KA value. Changes in the concentration of the enzyme have no effect. Under assay conditions approaching the ionic, buffer, and substrate concentrations expected to occur in the mitochondrial matrix, the KA value for acetylglutamate is 27 microM and the Vmax is decreased about 50%. These results indicate that physiological changes in the level of acetylglutamate significantly influence the degree of activation of carbamoyl phosphate synthetase in vivo. PMID- 1898039 TI - Inhibition of ethanol metabolism by fructose in alcohol dehydrogenase-deficient deer mice in vivo. AB - The purpose of this work was to compare the roles of a newly described mitochondrial dehydrogenase and catalase in ethanol elimination in deer mice deficient in alcohol dehydrogenase (ADH-). Fructose was used because of its well known ability to stimulate dehydrogenase-dependent ethanol metabolism. Rates of ethanol metabolism in vivo were decreased significantly by about 60% in a dose dependent manner by fructose in deer mice fed an ethanol-containing or a corn oil control diet. In addition, rates of metabolism of methanol, a selective substrate for catalase in rodents, were similar to rates of ethanol elimination and were decreased from 6.9 +/- 1.0 to 1.7 +/- 0.5 mmol/kg/h by fructose, supporting the hypothesis that catalase and not a mitochondrial dehydrogenase predominates in ethanol oxidation in ADH-deer mice. Glycolate, a substrate for peroxisomal H2O2 generation, reversed the inhibition of alcohol metabolism by fructose completely, indicating that fructose did not inhibit catalase directly. As expected, the ATP/ADP ratio was decreased by fructose significantly from 4.2 +/- 0.4 to 2.4 +/- 0.4 in deer mouse livers. These data are consistent with the hypothesis that fructose decreases catalase-dependent ethanol metabolism in vivo by inhibiting hepatic H2O2 generation. PMID- 1898040 TI - Modification of hepatic vitamin E stores in vivo. II. Alterations in plasma and liver vitamin E content by 1,2-dibromoethane. AB - Previous studies with methyl ethyl ketone peroxide (MEKP), a radical generator, showed depletion of plasma vitamin E and liver glutathione (GSH) levels prior to a decrease of liver vitamin E levels. Since hepatic pools of this vitamin may serve to maintain circulating levels of vitamin E under conditions of oxidative challenge, we have evaluated the similarity of response after treatment with 1,2 dibromoethane (DBE), a compound that is not known to generate oxyradicals or to induce lipid peroxidation in vivo. Treatment of normal rats with DBE caused a depletion in hepatic vitamin E levels 1 day after treatment; however, in contrast to our prior findings with MEKP this depletion after DBE treatment was observed in tandem with elevations in the plasma content of vitamin E. Liver vitamin E depletion was neither dependent upon a sustained liver GSH depletion nor upon hepatocellular death. Mobilization and export of hepatic vitamin E did not result in an immediate whole body redistribution of this vitamin in that pulmonary and renal levels of vitamin E remained normal under conditions of liver vitamin E depletion. Moreover, the stimulus that resulted in exportation of liver vitamin E was maintained by daily treatments with DBE. DBE caused a substantial elevation above control values in liver GSH content and these elevations were also maintained by daily DBE treatments. In experiments to assess the influence of prandial replacement of vitamin E on the extent of depletion in response to DBE treatment, rats were fed a vitamin E-deficient diet for 2 days prior to treatment. This short pulse of a vitamin E-deficient diet delayed (to 2 days) both the elevation in liver GSH content and the depletion of liver vitamin E and hastened (to 1 day) the elevation in plasma vitamin E concentration. These observations suggest the presence of at least two pools of liver vitamin E and that one of these pools, which comprises at least 30% of the total hepatic vitamin E content, is able to be mobilized and exported in response to chemical challenge. The stimulus that resulted in liver vitamin E exportation in response to DBE treatment seems to result from wholly intrahepatic processes and may not be a direct response to lipid peroxidation. Moreover, the similarity between the time-course and the extent of hepatic vitamin E depletion observed after treatment with either MEKP or DBE suggests a similarity in physiochemical processes that function to mobilize hepatic vitamin E stores. PMID- 1898042 TI - Evidence suggesting a role for cathepsin L in an experimental model of glomerulonephritis. AB - We have utilized specific, irreversible inhibitors of cysteine proteinases to examine the role of renal cathepsin B and cathepsin L in the proteinuria which occurs in an experimental model of human glomerular disease. Administration of trans-epoxysuccinyl-L-leucylamido-(3-methyl)butane (Ep475) a specific, irreversible inhibitor of cysteine proteinases, including cathepsins B and L, significantly reduced proteinuria in rats with experimentally induced, neutrophil independent, anti-GBM antibody disease (controls: 10 +/- 1 mg/24 h, N = 8; anti GBM antibody disease: 203 +/- 30 mg/24 h, N = 8; anti-GBM antibody disease + Ep475: 112 +/- 13 mg/24 h, mean +/- SEM, N = 6, P less than 0.05). There was a marked reduction in the activity of both cathepsin B and cathepsin L in renal cortices obtained from Ep475-treated rats compared to either saline-treated controls or rats treated with anti-GBM IgG only. Administration of Z-Phe-Tyr(O-t butyl)CHN2, a specific, irreversible cysteine proteinase inhibitor with a high degree of selectivity toward cathepsin L, also caused a reduction in anti-GBM antibody-induced proteinuria (90 +/- 18 mg/24 h, N = 6, P less than 0.05). This reduction in proteinuria was accompanied by a marked decrease (-84%) in the specific activity of renal cortical cathepsin L in Z-Phe-Tyr(O-t-butyl)CHN2 treated rats. However, cathepsin B activity was unchanged. There was no significant change in the renal anti-GBM antibody uptake, plasma urea nitrogen, or plasma creatinine values in the Z-Phe-Tyr(O-t-butyl)CHN2-treated rats compared to rats treated with anti-GBM IgG only or saline-treated controls. These data document the ability of cysteine proteinase inhibitors to decrease the proteinuria which occurs in a neutrophil-independent model of human anti-GBM antibody disease and suggest an important role for cathepsin L in the pathophysiology of the proteinuria which occurs in this model. PMID- 1898041 TI - Modification of hepatic vitamin E stores in vivo. III. Vitamin E depletion by 1,2 dibromoethane may be related to initial conjugation with glutathione. AB - In the companion paper we demonstrated that hepatic vitamin E in rats becomes depleted and extrahepatic pools of vitamin E are altered by treatment with 1,2 dibromoethane (DBE). Vitamin E depletion may be dependent upon initial steps of DBE metabolism that are either oxidative (cytochrome P450 dependent) or conjugative (glutathione transferase dependent). That the liver content of glutathione (GSH) and vitamin E, the plasma concentration of vitamin E, and the serum activities of AST and ALT may be influenced by cytosolic metabolism of DBE was assessed by comparison of findings from rats treated with either 1,2 dichloroethane (DCE) or 1-bromo-2-chloroethane (BCE). The extent of oxidative metabolism was diminished by the use of tetradeutero-DBE (d4-DBE), and the availability of GSH for conjugative metabolism was diminished by pretreatment of rats with L-buthionine-S,R-sulfoximine (BSO) prior to treatment with DBE. Our results indicate that neither DCE nor BCE provokes a liver vitamin E depletion in rats, that d4-DBE treatment hastens but does not enhance the observed hepatic vitamin E depletion by comparison to animals treated with an equimolar dose of DBE, and that BSO pretreatment prevented the hepatic vitamin E depletion observed from animals treated with DBE alone. These results indicate that hepatic vitamin E depletion is the unique sequelae to conjugation of GSH with DBE, and we suggest the reactive episulfonium ion intermediate or a macromolecular adduct of this ion derived from DBE may play a role in liver vitamin E depletion associated with exposure to DBE. PMID- 1898043 TI - The role of nonenzymatic glycosylation, transition metals, and free radicals in the formation of collagen aggregates. AB - Incubation of corneal collagen type I with glucose in the presence of transition metal ions (copper, iron) results in the formation of collagen aggregates insoluble in 6 M urea, and in 2% sodium dodecyl sulfate + 5% beta mercaptoethanol. The reaction is mediated by hydrogen peroxide and transition metals since it is inhibited by catalase and by the chelating agent diethylenetriaminepentaacetic acid. Comparative studies showed that copper is more efficient than iron and that the reaction proceeds more rapidly with ribose than with glucose. The data support a mechanism involving transition metal ion catalyzed autoxidation of glucose (and possibly of Amadori products) with generation of superoxide radical. Superoxide dismutation produces hydrogen peroxide, which then generates hydroxyl radicals in the presence of transition metal ions (Fenton reaction). Hydroxyl radical attack is known to lead to cross linking, which is enhanced in glycated proteins. The experimental data presented are consistent with in vivo alteration of collagen properties during normal aging and with the acceleration of similar changes in diabetes mellitus. PMID- 1898044 TI - Increase in fidelity of rat liver Ile-tRNA formation by both spermine and the aminoacyl-tRNA synthetase complex. AB - To examine the polyamine effects on the fidelity at the aminoacylation level and the physiological significance of the existence of the aminoacyl-tRNA synthetase complex (ARSC) in animal cells, a single-chain Ile-tRNA synthetase (IRSS) was isolated from the complex by treatment with trypsin. Ile-tRNA formation by IRSS was strongly stimulated by spermine, similar to the results with ARSC. Two misacylations (Val-tRNAIle and Ile-tRNAiMet formation) by IRSS were measured. The error frequency was higher in Ile-tRNAiMet formation (tRNA misacylation) than in Val-tRNAIle formation (amino acid misacylation). Spermine did not influence significantly Ile-tRNAiMet formation, but it stimulated Val-tRNAIle formation by IRSS. Accordingly, spermine decreased the error frequency of tRNA misacylation, but not amino acid misacylation. These results suggest that the conformational changes of individual tRNA by spermine differ from each other, meaning that spermine influences the interaction between individual tRNA and aminoacyl-tRNA synthetase variously. When the aminoacylations of tRNAIle from rat liver, yeast, and Escherichia coli were compared with ARSC and IRSS, the relative speed of Ile tRNA formation with tRNAIle from other species was faster with IRSS than with ARSC. This indicates that ARSC can recognize tRNAIle from the same species more specifically than IRSS. These results show that both spermine and ARSC are involved in the increase of fidelity of rat liver Ile-tRNA formation. PMID- 1898046 TI - Determination of the phosphorylation sites of smooth muscle caldesmon by protein kinase C. AB - Smooth muscle caldesmon was phosphorylated by protein kinase C up to 1.90 mol P/mol caldesmon. Phosphorylated caldesmon was completely digested by trypsin and the produced phosphopeptides were purified by C-8 and C-18 reverse phase chromatography. Four phosphopeptides were determined and two phosphoserines were identified. Both were localized in the C-terminal domain at serine-587 and serine 726. By following the time course of phosphorylation, serine-587 was found to be the preferred site. Effects of the phosphorylation of caldesmon by protein C on the inhibition of acto-H-meromyosin ATPase activity was also examined. While unphosphorylated caldesmon inhibited the ATPase activity by 60%, phosphorylated caldesmon hardly inhibited the ATPase activity. Therefore, it was concluded that the phosphorylation at serine-726 and serine-587 reverses the inhibitory activity of caldesmon. PMID- 1898045 TI - Fatty acyl CoA-dependent and -independent retinol esterification by rat liver and lactating mammary gland microsomes. AB - Retinol esterification was examined in microsomes from rat liver and lactating mammary gland as a function of the form of retinol substrate, dependence on fatty acyl CoA, and sensitivity to phenylmethylsulfonyl fluoride (PMSF). Retinol bound to cellular retinol-binding protein (CRBP) or dispersed in solvent was esterified in a fatty acyl CoA-independent, PMSF-sensitive reaction, consistent with lecithin:retinol acyltransferase (LRAT) activity. LRAT activity exhibited the same Km (2 microM retinol) between tissues but a higher Vmax in liver as compared to that in mammary gland (47 vs 8 pmol/min/mg microsome protein, respectively). Solvent-dispersed retinol was also esterified in a fatty acyl CoA-dependent, PMSF resistant reaction, consistent with acyl CoA:retinol acyltransferase (ARAT) activity. Retinol bound to CRBP was not a good substrate for this reaction. ARAT activity displayed a similar Vmax (300 pmol/min/mg microsome protein) between tissues but Km values of 15 and 5 microM for retinol and fatty acyl CoA in mammary gland as compared to 30 and 25 microM, respectively, in the liver. Thus, when substrate was near or below Km, retinol esterification occurred predominantly by LRAT in the liver and ARAT in the mammary gland, respectively. The concentration of CRBP in the cytosol, determined by Western blotting, was approximately 2 microM in the liver but was almost nondetectable in the mammary gland. These data suggest that retinol esterification is regulated via different mechanisms in liver and mammary gland and support a specific role for CRBP in the liver. PMID- 1898047 TI - Sodium dodecyl sulfate and heat induce two distinct forms of lobster muscle multicatalytic proteinase: the heat-activated form degrades myofibrillar proteins. AB - A multicatalytic proteinase (MCP) purified from lobster claw and abdominal muscles degrades a variety of peptide and protein substrates. The enzyme is activated by low concentrations (0.03%) of sodium dodecyl sulfate (SDS) and brief (1 min) heating at 60 degrees C. The lobster MCP can assume three stable and functionally distinct states in vitro; these are classified as the basal, heat activated, and SDS-activated forms. The basal MCP possessed high trypsin-like peptidase activity and low chymotrypsin-like peptidase, peptidylglutamyl-peptide hydrolase, and caseinolytic activities; incubation of the basal form with SDS stimulated the peptidylglutamyl-hydrolase activity about 30-fold and inhibited the other three activities 80% to 100%. Heating the basal form stimulated caseinolytic activity about 6-fold with little effect on the peptidase activities. The heat-activated enzyme also degraded myosin, tropomyosin, troponin, and actin depolymerizing factor; alpha-actinin was resistant to proteolysis. Incubation of the heat-activated MCP with SDS inhibited the trypsin like, chymotrypsin-like, and proteinase activities 95 to 100% and stimulated the peptidylglutamyl-hydrolase activity about 16-fold. Incubation of myosin with either the basal or the heat-activated forms in the presence of SDS generated identical proteolytic fragments of the myosin heavy chain, suggesting that SDS induced a third form that can be produced from either the basal or the heat activated forms. The heat-activated form produced proteolytic fragments of myosin heavy chain different from those generated by either basal or heat-activated enzymes in the presence of SDS. Furthermore, 100 mM KCl stimulated the caseinolytic activity of the heat-activated form 24% and inhibited the trypsin like and peptidylglutamyl-hydrolase activities 56 and 20%, respectively. These results, though indirect, suggest that heating induced a proteinase activity that was distinct from the three peptidase activities. Activation of the basal form with SDS was reversible, since precipitation of dodecyl sulfate with 100 mM KCl restored trypsin-like activity and inhibited peptidylglutamyl-hydrolase activity. In contrast, removal of dodecyl sulfate from the SDS-activated form that was derived from the heat-activated MCP induced its conversion to the basal form. Thus, although heat-activation was irreversible, the heat-activated form was converted back to the basal form via the SDS-activated form. PMID- 1898048 TI - Coordinate- and elicitor-dependent expression of stilbene synthase and phenylalanine ammonia-lyase genes in Vitis cv. Optima. AB - The mechanisms controlling the induction of stilbene synthase and phenylalanine ammonia-lyase (PAL), two putative key regulatory enzymes of the biosynthetic pathway to stilbene phytoalexins, have been investigated. The induction was studied in cell suspension cultures of grape (Vitis cv. Optima) by treatment with fungal cell wall. Several independent cDNA clones for PAL and stilbene synthase were isolated from a cDNA library of fungal cell wall-induced grape cells and identified by sequence analysis. The stilbene synthase cDNA sequence of pSV21 predicted a protein of 392 amino acids and Mr 42,791, similar in size to that observed experimentally for immunodetected stilbene synthase. The cDNA sequences of pSV21 and pSV25 differed in 76 bp in the coding region. The sequences of grape stilbene synthase cDNAs exhibited significant homology to the sequence reported for the peanut stilbene synthase cDNA. Both PAL and stilbene synthase mRNA, measured by RNA blot hybridizations, were induced within 1 h of addition of fungal cell wall preparations to the cell cultures, rose to a maximum by the sixth hour, then declined slowly over the next 20 h. The activities of PAL and stilbene synthase were also induced in parallel, but reached their maximum at different times after fungal cell wall addition to the cell cultures. The induction patterns of stilbene synthase and PAL in grape and peanut are discussed. PMID- 1898049 TI - A proteolytic fragment of the oxysterol receptor which retains oxysterol binding activity. AB - The structural organization of the oxysterol receptor, postulated to be involved in the regulation of 3-hydroxy-3-methylglutaryl CoA reductase and cholesterol biosynthesis in mammalian cells, has been explored by limited proteolysis with trypsin, alpha-chymotrypsin, and endoproteinase GluC. Treatment with each of these proteases converts the receptor from a homodimer of approximately 95 kDa subunits to a 44-kDa form, based on hydrodynamic measurements by sucrose density gradient centrifugation and gel filtration chromatography. Sodium dodecyl sulfate polyacrylamide gel electrophoresis of photoaffinity-labeled preparations indicates that the oxysterol binding site is on a 28-kDa fragment within the 44 kDa limit form of the receptor. The limit proteolytic form exhibits the high affinity and structural specificity for oxysterols of the native dimeric receptor with an increase in the rate constant of association for 25-hydroxycholesterol. The proteolytic form also shows an increased binding affinity for nonspecific DNA, but no sequence specificity for the oxysterol regulatory element from the reductase gene was detected. PMID- 1898050 TI - Retinyl ester hydrolases in retinal pigment epithelium. AB - In bovine retinal pigment epithelium membranes we have found three hydrolases which were active against trans-retinyl palmitate. This was possible by assaying different subcellular fractions as a function of pH in the range 3-9. Detection of these activities has been favored by the use in the enzyme assay of Triton X 100, which has an activating effect up to a concentration of 0.03% at a detergent protein ratio of about 1.5-3.0. Apparent kinetic parameters for the retinyl ester hydrolases have been determined after a study of the optimization of assay conditions. Vmax values for hydrolases acting at pH 4.5, 6.0, and 7.0 were, respectively, 156, 55, and 70 nmol/h/mg. To identify the subcellular site for these hydrolytic activities, assays of marker enzymes from various organelles in each subcellular preparation were carried out, demonstrating the lysosomal origin of the pH 4.5 retinyl ester hydrolase and the microsomal origin of the pH 6.0 retinyl ester hydrolase and suggesting that the pH 7.0 retinyl ester hydrolase originates from the Golgi complex. PMID- 1898051 TI - Biosynthesis of the unique trans-delta 3-hexadecenoic acid component of chloroplast phosphatidylglycerol: evidence concerning its site and mechanism of formation. AB - As in most higher plants, chloroplast membranes of the green alga Dunaliella salina contain phosphatidylglycerol (PG) that is rich in trans-delta 3 hexadecenoic acid (16:1t), a fatty acid found nowhere else in the cell. After labeling D. salina with exogenous [3H]myristic acid [( 3H]14:0), the cis unsaturated fatty acids of monogalactosyldiacylglycerol and sulfoquinovosyldiacylglycerol as well as PG had higher specific radioactivities in chloroplast envelopes than in thylakoids. In contrast, 16:1t was very slow to become radioactive, and its specific radioactivity was several times higher in isolated thylakoids than in envelopes after brief (3-20 min) labeling with [3H]14:0. Analysis of individual PG molecular species revealed that the fatty acid paired with 16:1t was also labeled slowly. Thus linoleate (18:2) released from a 16:1t-containing PG had a 350-fold (at 3 min) to 20-fold (at 60 min) lower specific radioactivity than did 18:2 from a palmitate (16:0)-containing PG. The findings suggest that the substrates for trans-desaturation are 16:0-containing PG molecular species which are readily labeled from [3H]14:0 in the envelope but are diluted by the large pool of thylakoid PG before penetrating to the desaturation site. By examining the labeling patterns of individual PG molecular species classes, it was concluded that D. salina 16:1t is formed from 16:0 linked to 18:2/16:0 PG and 18:3/16:0 PG by a trans-desaturase located within the inner recesses of the thylakoid compartment. PMID- 1898052 TI - Acylation of alkyllysophospholipids by Fischer sarcoma microsomes. AB - Acylation of alkyllysophospholipids in most cells occurs by: (a) CoA-independent transacylation, (b) CoA-dependent transacylation, and (c) acyl-CoA-dependent acylation. Using a recently developed high-performance liquid chromatography method, we have investigated the factors that influence the molecular species composition of the acylated products formed via these pathways with 1-hexadecyl-2 lyso-sn-glycero-3-phosphocholine (alkyllyso-GPC) or 1-hexadecyl-2-lyso-sn-glycero 3-phospho-ethanolamine (alkyllyso-GPE) as substrates for the enzymes in Fischer R 3259 sarcoma microsomes. We found that short incubation times and low substrate concentrations favored the formation of polyunsaturated molecular species, i.e., 16:0-22:6, 16:0-22:5 (n - 3), and 16:0-20:4. Also, in agreement with results from other systems, CoA-independent transacylation produced a high percentage of polyunsaturated molecular species; acyl-CoA-dependent acylations generated the least polyunsaturated molecular species and CoA-dependent transacylation gave intermediate values. Furthermore, no substrate selectivity occurred with respect to alkyl chain lengths of alkyllyso-GPE; similar molecular species composition was obtained with either hexadecyllyso-GPE or octadecyllyso-GPE as substrates. Responses to N-ethylmaleimide inhibition and heat inactivation as well as pH optima suggest the same enzyme catalyzes the CoA-independent transacylation of both alkyllyso-GPC and alkyllyso-GPE. PMID- 1898053 TI - Isolation and characterization of a homogeneous isoenzyme of wheat germ acid phosphatase. AB - An acid phosphatase (orthophosphoric monoester phosphohydrolase, acid optimum; EC 3.1.3.2) isoenzyme from wheat germ was purified 7000-fold to homogeneity. The effect of wheat germ sources and their relationship to the isoenzyme content and purification behavior of acid phosphatases was investigated. Extensive information about the purification and stabilization of the enzyme is provided. The instability of isoenzymes in the latter stages of purification appeared to be the result of surface inactivation together with a sensitivity to dilution that could be partially offset by addition of Triton X-100 during chromatographic procedures. Added sulfhydryl protecting reagents had no effect on activity or stability, which was greatest in the pH range 4-7. The purified isoenzyme was homogeneous by polyacrylamide gel electrophoresis and exhibited the highest specific activity and turnover number reported for any acid phosphatase. The molecular weights of the pure isoenzyme and of related isoenzymes from wheat germ were found to be identical (58,000). The pure isoenzyme contained a single polypeptide chain and had a negligible carbohydrate content. The amino acid composition was determined. Of the various reasons that were considered to explain isoenzyme occurrence, a genetic basis was considered most likely. The enzyme was found to exhibit substrate inhibition with some substrates below pH 6, while above pH 8 it exhibited downwardly curving Lineweaver-Burk plots of the type that are generally described as "substrate activation". The observation of a phosphotransferase activity was consistent with the formation of a covalent phosphoenzyme intermediate, while inactivation by diethyl pyrocarbonate was consistent with the presence of an active site histidine. PMID- 1898054 TI - Identification of two calpastatin forms in rat skeletal muscle and their susceptibility to digestion by homologous calpains. AB - Two forms of calpastatin, differing in their specificity for the homologous calpain isozymes I and II, have been separated from rat skeletal muscle extracts and purified to homogeneity. Calpastatin I, the first form to elute in chromatography on DE32, is more effective against calpain I, while calpastatin II is more effective as an inhibitor of calpain II. Based on their molecular mass (approximately 105 kDa) both calpastatin forms belong to the high molecular mass class found in muscles of other animal species (Murachi, T., 1989, Biochem. Int. 18, 263-294). For calpain I, which is active with low (mu-M) concentrations of Ca2+, maximum inhibition with either calpastatin form was observed over a wide range of Ca2+ concentrations. With calpain II, which requires high (mM) concentrations of Ca2+ for activity, maximum inhibition required Ca2+ concentrations above 1 mM. Both calpastatin forms were found to be highly sensitive to degradation by calpain II, but almost completely resistant to degradation by calpain I. Degradation of calpastatin by calpain II is competitively inhibited by the addition of a calpain substrate. Isovaleryl carnitine (IVC), an intermediate product of L-leucine catabolism, previously demonstrated to be a potent and specific activator of rat skeletal muscle calpain II (Pontremoli, S., Melloni, E., Viotti, P. L., Michetti, M., Di Lisa, F., and Siliprandi, N., 1990. Biochem. Biophys. Res. Commun. 167, 373-380) greatly enhances the rate of degradation of calpastatins by calpain II. IVC, which decreases the Ca2+ requirement for maximal calpain II activity, also decreases the concentration of Ca2+ required for digestion of the inhibitor. For calpain II, regulation by either calpastatins may occur only in the presence of high [Ca2+]. PMID- 1898055 TI - Salivary cystatin SA-III, a potential precursor of the acquired enamel pellicle, is phosphorylated at both its amino- and carboxyl-terminal regions. AB - Cystatin SA-III was purified from human submandibular/sublingual glandular secretions by adsorption to hydroxyapatite, gel filtration chromatography, and reversed-phase HPLC. The amino acid sequence of its amino-terminus was deduced by sequential Edman degradation and found to be identical to the first 10 residues of cystatin HSP-12. The purified protein was digested with endoproteinase Asp-N and the digestion products were subjected to fast atom bombardment mass spectroscopy. m/z values corresponding to 12 peptides were aligned to the sequence of cystatin S preceded by the eight-residue amino-terminal peptide detected in HSP-12. This process resulted in the assignment of peptides corresponding with 118 out of the 121 amino acid residues predicted from the nucleotide sequence for cystatin SA-III. In order to align several peptides, it was necessary to substitute four residues of phosphoserine for four residues of serine. Fast atom bombardment mass spectrometry and additional Edman degradation procedures localized the phosphate moieties to Ser-3, Ser-99, Ser-112, and Ser 116. This is the first report of the structure of cystatin SA-III deduced by amino acid sequencing techniques and indicates the sites of phosphoserine within the molecule. Based on these assignments, cystatin SA-III is unique among salivary proteins in that it possesses phosphate groups at its amino-terminus as well as its carboxyl-terminus. PMID- 1898056 TI - Lethal damage to murine L1210 cells by exogenous lipid hydroperoxides: protective role of glutathione-dependent selenoperoxidases. AB - The effect of selenium deprivation on the viability of murine L1210 cells exposed to various exogenous lipid hydroperoxides has been investigated. Selenoperoxidase activities of cells grown for longer than 1 week in 1% serum with no added selenium [Se(-) cells] were less than 10% of the activities of selenium-satisfied controls [Se(+) cells] or selenium-repleted counterparts [Se(-/+) cells]. The enzymes measured were classical glutathione peroxidase (GPX) and phospholipid hydroperoxide glutathione peroxidase (PHGPX). Se(-) cells exhibited a compensatory increase in catalase activity. Dye exclusion and clonal survival assays indicated that Se(-) and Se(+) cells were relatively insensitive to photochemically generated phospholipid hydroperoxides in liposomal form. However, both cell types were sensitive to liposomal cholesterol hydroperoxides, e.g., 7 hydroperoxycholesterol (7-OOH), Se(-) being much more so (LD50 approximately 10 microM) than Se(+) (LD50 approximately 75 microM). By contrast, 7 hydroxycholesterol over a comparable concentration range was minimally toxic to Se(-) and Se(+) cells. Cell killing by 7-OOH was inhibited by desferrioxamine and by butylated hydroxytoluene, suggesting that iron-mediated free radical reactions are involved. The involvement of glutathione in cytoprotection was confirmed by showing that Se(+) cells were more sensitive to 7-OOH after treating with buthionine sulfoximine, an inhibitor of GSH synthesis. Cellular detoxification of 7-OOH is provisionally attributed to PHGPX rather than GPX, since 7-OOH and other cholesterol hydroperoxides were found to be good substrates for PHGPX in a cell free system, but were unreactive with GPX. PMID- 1898057 TI - Detection of a trypsin-like serine protease and its endogenous inhibitor in hake skeletal muscle. AB - When dialyzed extracts from hake (Merluccius hubbsi) skeletal muscle were chromatographed in DEAE-Sephacel, an alkaline protease (37 degrees C, pH 8.5) and a trypsin inhibitor were isolated. The enzyme showed its maximal activity against azocasein in the range of pH between 7 and 9. The protease was able to hydrolyze the trypsin substrates Bz-Arg-OEt and Tos-Arg-OMe and did not cleave the chymotrypsin substrate Bz-Tyr-OEt. The enzyme was strongly inhibited by several serine protease inhibitors, whereas inhibitors of the other types of proteases scarcely affected it. The protease was able to degrade the major contractile and cytoskeletal constituent proteins of myofibrils and to accumulate acid-soluble products. The protease activity was completely suppressed by the addition of the trypsin inhibitor isolated from the same muscle. These results indicate that hake skeletal muscle contains a trypsin-like serine protease which might be involved in the catabolism of myofibrillar proteins, as well as in the proteolytic events that take place during post mortem storage of fish muscle. PMID- 1898058 TI - Hill coefficient ratios give binding ratios of allosteric enzyme effectors; inhibition, activation, and squatting in deoxycytidylate aminohydrolase (EC 3.5.4.12) AB - The ratio of the steady-state kinetic Hill coefficients of two different effectors equals (under some rather weak general assumptions) the ratio in which the effectors displace each other from an enzyme. This principle can make implications of experimental allosteric enzyme kinetic data immediately apparent. We can use it to find that one molecule of the allosteric inhibitor of dCMP aminohydrolase, at moderately high effector concentrations, displaces one molecule of substrate, or one molecule of activator, whereas at very high concentrations, one molecule of inhibitor displaces two of substrate. Further use of the principle suggests that substrate, at high concentrations, binds binds to activator sites. However, ratios of substrate, activator, and inhibitor Hill coefficients are incompatible with a simple model of activation in which substrate and activator are bound to the same conformation. PMID- 1898059 TI - The pH dependence of the action pattern in porcine pancreatic alpha-amylase catalyzed reaction for maltooligosaccharide substrates. AB - Porcine pancreatic alpha-amylase (EC 3.2.1.1; abbreviated PPA), which hydrolyzes alpha-D-(1,4) glucosidic bonds in starch and amylose, displays an optimum at pH 6.9 for the majority of substrates. The optimum pH, however, shifted to 5.2 for the hydrolysis of some low molecular substrates (Ishikawa, K., et al., 1990, Biochemistry 29, 7119-7123). Details of the substrate-dependent shift of the optimum pH in PPA were studied by use of a series of maltooligosaccharides with 14C-labeled reducing end glucose as substrates. The optimum pH for maltotriose was 5.2, whereas that for maltopentaose and maltohexaose was unchanged at pH 6.9. The pH profile for the intermediate size substrate maltotetraose showed abnormality; the apparent optimum pH was broadened between 5.5 and 6.5 and the bond cleavage pattern depended on pH, unlike that for the other substrates examined. These results were independent of either buffer systems or substrate concentration. Analyses of the hydrolysates of the maltooligosaccharides revealed that the shift of the optimum pH to the neutral region occurred only when the fifth subsite of PPA in the productive binding modes was occupied by a glucosyl residue of a substrate. The three-catalytic residue model of PPA deduced from the analysis of the hydrolysis of some modified maltooligosaccharides (p-nitrophenyl alpha-D-maltoside, gamma-cyclodextrin, maltopentaitol, and maltohexaitol) (Ishikawa, K., et al., 1990, Biochemistry 29, 7119-7123) was successfully adapted to the linear maltooligosaccharides used in this work. These results indicate that the different productive binding modes of the linear oligosaccharide substrates affect directly the catalytic power and the optimum pH of PPA. PMID- 1898060 TI - Physical studies on membrane lipids of Bacillus stearothermophilus temperature and calcium effects. AB - Bacillus stearothermophilus was grown at the optimal temperature range (center, 65 degrees C), below it (48 and 55 degrees C), and above it (68 degrees C), in a complex medium with or without 2.5 mM Ca2+. The Ca(2+)-supplement improves growth at sub- and supraoptimal temperatures and extends it to higher temperatures (Jurado et al. (1987) J. Gen. Microbiol. 133, 507-513). The phospholipid composition of cultures obtained in the different growth conditions was studied. Phosphatidylethanolamine was always the major phospholipid (40 to 50% of the total phospholipid). Diphosphatidylglycerol, phosphatidylglycerol, a phosphoglycolipid (pgl) and two minor phospholipids (not identified) were also found in the polar lipid extract. The pgl shows a threefold concentration increase as the growth temperature raises from 48 to 68 degrees C. The thermotropic behavior of membrane lipids was studied by differential scanning calorimetry (DSC) and by means of two fluorescent probes of fluidity, 1,6 diphenyl-1,3,5-hexatriene (DPH) and 1,3-di(2-pyrenyl)propane (2Py(3)2Py). The results reveal similar features and clearly show a shift of the temperature range of the phase transition to higher values and an increased structural order of the bilayer, as the growth temperature rises from 55 to 68 degrees C, but an opposite effect was observed from 48 to 55 degrees C. Although the Ca(2+)-supplement to the growth medium has no detectable effect, the addition of Ca2+ to the buffer of liposomes (Ca(2+)-liposomes) has a significant ordering effect at all growth temperatures. These liposomes show a shift of the transition range to higher temperatures and the fluorescent parameters (DPH polarization and intramolecular excimerization of the 2Py(3)2Py) detected an order increase of the probes environment, along and above the main phase transition. Spectra of 31P-NMR and polarized light microscopy clearly show that the lipid extracts exhibit, in all the conditions, typical lamellar phase geometry. We concluded that B. stearothermophilus controls the membrane lipid composition to compensate for the destabilizing effect of high temperatures on the membrane organization or to provide an appropriate packing of phospholipid molecules in a stable bilayer. At high temperatures, Ca(2+)-stimulatory effect on growth is presumably due to a direct Ca2+ interaction with the membrane phospholipids, inducing an increased structural order on the bilayer. The increase of the phase transition temperature in the total lipid extracts as compared with the respective polar lipid fractions probably indicates a stabilizing effect of neutral lipids on membrane bilayers. PMID- 1898061 TI - Allosteric modifier and substrate binding of donkey deoxycytidylate aminohydrolase (EC 3.5.4.12) AB - The hexameric allosteric enzyme deoxycytidylate aminohydrolase from donkey spleen is shown by equilibrium dialysis to bind specifically the allosteric inhibitor, dTTP, the activator dCTP, and the substrate analog dAMP each at six sites (the dTTP and dCTP sites may or may not be identical). These conclusions contrast with earlier ones that there were four sites for each effector; reasons for the discrepancy are discussed. With the knowledge of site numbers and the kinetic information from the accompanying paper it is concluded that the kinetic cooperativity of the enzyme excludes a concerted conformational transition mechanism. Amino acid analysis gives a molecular weight of 18,842 Da per subunit, i.e., 113,052 for the hexamer. A new simplified purification of homogeneous enzyme from donkey spleen probably useful for dCMP aminohydrolase from other sources is described. PMID- 1898062 TI - Recombinant type A rat 75-kDa alpha-amidating enzyme catalyzes the conversion of glycine-extended peptides to peptide amides via an alpha-hydroxyglycine intermediate. AB - The amidation of C-terminal glycine-extended peptides has been analyzed by the use of a truncated type A peptidylglycine alpha-amidating enzyme (alpha-AE) encoded by cDNA prepared with RNA from rat medullary thyroid carcinoma (MTC) cells. Mouse C127 cells transfected with the rat MTC cDNA encoding the truncated type A alpha-AE secrete the expected 75-kDa enzyme into the culture medium. Medium conditioned with the transfected C127 cells converts both dansyl-Tyr-Val Gly and dansyl-Tyr-Val-alpha-hydroxyglycine to dansyl-Tyr-Val-NH2 at levels which are approximately 1000 times higher than the levels found in medium conditioned with untransfected C127 cells. This result indicates that rat type A alpha-AE alone catalyzes a two-step reaction involving an initial hydroxylation of peptidyl-Gly followed by conversion of the peptidyl-alpha-hydroxyglycine intermediate to the amidated product. The involvement of a separate, second enzyme to convert peptidyl-alpha-hydroxyglycine to peptidyl-NH2 is not necessary in this system. The initial hydroxylation step is rate-determining at infinite substrate concentration and requires a reducing equivalent, molecular oxygen, and copper. PMID- 1898063 TI - Interactions of triply phosphorylated human beta-casein: fluorescence spectroscopy and light-scattering studies of conformation and self-association. AB - Structural changes of triply phosphorylated human beta-casein, caused by shifts in temperature between 5 and 40 degrees C, were studied using intrinsic and extrinsic fluorescence, fluorescence polarization, turbidity, and light scattering measurements. Intrinsic fluorescence declined between 5 and 20 degrees C then rose between 25 and 40 degrees C, indicative of a shift of the tryptophan fluor toward a more nonpolar environment. The fluorescence of the extrinsic probe, 8-anilino-1-naphthalene-sulfonic acid (ANS), increased only slightly between 5 and 25 degrees C, and then more sharply between 25 and 40 degrees C, suggesting a change in conformation leading to a change in either the dissociation constant, Kd, or the number of ANS binding sites, N. The presence of Ca+2 ions did not significantly alter the pattern of changes of intrinsic and extrinsic fluorescence with changing temperature. For ANS binding, values of Kd and N were calculated by two different procedures, each based upon different assumptions. The results point to increased exposure of hydrophobic surfaces with increased temperature, strongly supportive of conformational changes. Although more opportunity for hydrophobic interaction leads to increased protein-protein association, turbidity and light-scattering also suggest ion bridge formation between protein molecules. A comparison of the primary sequences of beta-caseins from six species reveal residues that are common in all species examined and thus are pivotal in protein folding and conformation, intermolecular hydrophobic interactions and ion bridge formation with Ca+2 and inorganic phosphate. PMID- 1898064 TI - Modulation of collagen synthesis by growth factors: the role of ascorbate stimulated lipid peroxidation. AB - Ascorbic acid has been shown to stimulate collagen synthesis through induction of lipid peroxidation leading to increased transcription of the collagen genes. The mechanism by which lipid peroxidation stimulates collagen transcription is unknown; however, an alteration of cell membranes may affect the activity of serum growth factors leading to a change in gene expression. To test this hypothesis, we treated dermal fibroblasts with transforming growth factor-beta (TGF-beta), epidermal growth factor (EGF), interleukin-1 (IL-1), platelet-derived growth factor (PDGF), or fibroblast growth factor (FGF) in the presence of lipid peroxidation stimulating (200 microM) and nonstimulating (1 microM) concentrations of ascorbic acid. EGF and IL-1 had no effect on collagen synthesis at either concentration of ascorbic acid. FGF affected collagen synthesis only in the presence of 200 microM ascorbic acid, producing both a stimulation (0.4-2 ng/ml) and an inhibition (greater than 50 ng/ml). PDGF and TGF-beta stimulated collagen synthesis in the presence of both concentrations of ascorbic acid, with TGF-beta producing an 11-fold increase in collagen synthesis in the presence of ascorbate. This synergism produced by the combination of ascorbic acid and TGF beta was inhibitable by the lipid peroxidation inhibitor, propyl gallate. These results indicate that regulation of collagen synthesis by ascorbic acid does not occur through altering the response to EGF or Il-1. Ascorbate has no effect on PDGF but the effects of TGF-beta and FGF on collagen synthesis appear to be sensitive to lipid peroxidation. PMID- 1898065 TI - Reversible inactivation of recombinant rat liver guanidinoacetate methyltransferase by glutathione disulfide. AB - Recombinant rat liver guanidinoacetate methyltransferase is inactivated by glutathione disulfide (GSSG) following pseudo-first-order kinetics. A second order rate constant of 20.8 M-1 min-1 is obtained at pH 7.5 and 30 degrees C. The inactivation is fully reversed by glutathione (GSH) in a pseudo-first-order fashion with a second-order rate constant of 11.1 M-1 min-1. The rate of inactivation is not affected by S-adenosylmethionine or guanidinoacetate, but complete protection against inactivation is observed in the presence of sinefungin plus guanidinoacetate. At equilibrium in the buffers containing various concentrations of GSH and GSSG, the enzyme shows activities that are dependent on the ratio but not on the total concentration of GSH and GSSG. A hyperbolic relationship is obtained between enzyme activity and [GSH]/[GSSG] ratio. The inactivation by GSSG is associated with the disappearance of approximately 1 mol of sulfhydryl group per mole of enzyme. These results indicate that inactivation of guanidinoacetate methyltransferase by GSSG is the consequence of the formation of a mixed disulfide between a protein thiol and glutathione. The equilibrium constant for the redox reaction, E-SH + GSSG in equilibrium with E-SSG + GSH, obtained from the equilibrium data (1.69) is in good agreement with the value determined as the ratio of second-order rate constants for reactivation and inactivation (1.87). The cysteine residue engaged in the mixed disulfide with glutathione is identified as Cys-15 by peptide analysis after consecutive treatment of the GSSG-inactivated enzyme with N ethylmaleimide, 2-mercaptoethanol, and [14C]iodoacetate. The GSSG-inactivated enzyme binds S-adenosyl-methionine but not guanidinoacetate in the presence and absence of sinefungin. Native guanidinoacetate methyltransferase binds guanidinoacetate in the presence of sinefungin. The low overall redox equilibrium constant of 1.7-1.9 found for the reaction between guanidinoacetate methyltransferase and GSSG suggests that the activity of the enzyme is not amenable to modulation by the change in intracellular [GSH]/[GSSG] ratio. PMID- 1898066 TI - Purification and characterization of a fibrinolytic enzyme from venom of the southern copperhead snake (Agkistrodon contortrix contortrix). AB - A fibrinolytic enzyme present in Agkistrodon contortrix contortrix (southern copperhead) venom has been purified by combination of CM-cellulose chromatography, molecular sieve chromatography on Sephadex G-100, p aminobenzamidine-agarose affinity chromatography, and DEAE-cellulose chromatography. The enzyme, fibrolase, has a molecular weight of 23,000-24,000 and an isoelectric point of pH 6.8. It is composed of approximately 200 amino acids, possesses a blocked NH2-terminus and contains little or no carbohydrate. The enzyme shows no activity against a series of chromogenic p-nitroanilide substrates and is not inhibited by diisopropylfluorophosphate, soybean trypsin inhibitor, Trasylol, or p-chloromercuribenzoate. However, the enzyme is a metalloproteinase since it is inhibited by EDTA, o-phenanthroline and tetraethylenepentamine (a specific zinc chelator). Metal analysis revealed 1 mol of zinc/mol of protein. Study of cleavage site preference of the fibrinolytic enzyme using the oxidized B chain of insulin revealed that specificity is similar to other snake venom metalloproteinases with cleavage primarily directed to an X Leu bond. Interestingly, unlike some other venom fibrinolytic metalloproteinases, fibrolase exhibits little if any hemorrhagic activity. The enzyme exhibits direct fibrinolytic activity and does not activate plasminogen. In vitro studies revealed that fibrolase dissolves clots made either from purified fibrinogen or from whole blood. PMID- 1898068 TI - Purification and characterization of catalytically active precursor of rat liver mitochondrial aldehyde dehydrogenase expressed in Escherichia coli. AB - The cDNA coding for the precursor (p-ALDH) or mature (m-ALDH) rat liver mitochondrial aldehyde dehydrogenase was cloned in an expression vector pT7-7 and expressed in Escherichia coli strain BL21 (DE3)/plysS. The p-ALDH expressed in E. coli was a soluble tetrameric protein. It exhibited virtually the same specific activity and KmS for substrates as m-ALDH. N-terminal sequencing of isolated p ALDH provided the evidence that the catalytic activity was not derived from a partially processed mature-like enzyme. The assembly states of both p-ALDH and m ALDH synthesized in a rabbit reticulocyte lysate were also determined. Both of them were monomers and could not bind to a 5'-AMP-Sepharose column, showing that the monomeric form of the enzyme is inactive. The stabilities in vivo and in vitro were compared between p-ALDH and m-ALDH expressed in E. coli. p-ALDH was less stable than was m-ALDH both in vivo and in vitro. Thus, although the conformations of p-ALDH and m-ALDH are similar, the presence of signal peptide is a destabilizing factor to the p-ALDH. p-ALDH expressed in E. coli could bind to and be translocated into rat liver mitochondria, however, with lower efficiency when compared to the import of p-ALDH synthesized in reticulocyte lysate. PMID- 1898067 TI - Correlation of secondary structure with biological activity for a leader peptide: circular dichroism-derived structure and in vitro biological activities of preproparathyroid hormone peptide and its analogs. AB - Leader or signal sequences are specialized domains within precursor proteins which serve an essential role in interacting with the cellular secretory apparatus to enable intracellular transport and secretion of proteins. Despite many differences in primary amino acid sequences, signal domains interact with a common set of intracellular components, presumably because the signal sequences share an overall conformational similarity. In a few instances, mutant signal peptides from prokaryotes have been studied and their structures correlated with function (export) in vivo. A series of analogs of the precursor-specific region of preproparathyroid hormone have been prepared which contain substitutions of either proline or a charged amino acid within the hydrophobic core. These synthetic "mutants" have previously been evaluated in several in vitro assays to determine their functionality with regard to protein secretion and suitability as substrates for signal peptidase. The secondary structural content of each peptide, as well as the native sequence and sulfur-free analog, was determined in aqueous and nonaqueous conditions by circular dichroism (CD) as a function of time. The structures obtained were correlated with in vitro bioactivities. Unlike the findings or previous CD studies, all the peptides examined here had low to undetectable alpha-helical content in both aqueous and nonaqueous buffers. The unsubstituted and sulfur-free analogs had high (80-85%) beta-structure in aqueous conditions which was reduced to approximately 30% in nonaqueous solvent. The proline- and charged-substituted peptides contained about half the beta-structure content (35-55%) in aqueous buffer; in nonaqueous solvent their structure was similar to the unsubstituted peptides. The structure-activity correlates found were as follows: a high degree of structure (aqueous conditions) correlated with interaction with signal recognition particle and substrate suitability for signal peptidase; a low degree of structure (nonaqueous environment) correlated with activity in the translocation assay. PMID- 1898070 TI - Purification and characterization of alanine aminotransferase from Panicum miliaceum leaves. AB - Three alanine aminotransferases, two minor (AlaAT-1, AlaAT-3) and one major (AlaAT-2), were detected by native gel electrophoresis of leaf extracts from Panicum miliaceum L. AlaAT-2 was purified to homogeneity and a specific polyclonal antibody was raised against it which did not react with the other two forms of the enzyme. The enzyme, with an apparent molecular size of 102 kDa, appeared to be a dimer of a single 50-kDa polypeptide. The enzyme has a relatively broad pH optima with similar curves for the forward and reverse directions, ranging between 6.5 and 7.5. The Km values of this enzyme were 6.67, 0.15, 5.00, and 0.33 mM for alanine, 2-oxoglutarate, glutamate, and pyruvate, respectively. The activity of AlaAT-2 was found to increase markedly during leaf greening in parallel with the increase of immunochemically titrated protein, and it is suggested to function in the C4 photosynthetic cycle. PMID- 1898069 TI - Two genes encode the two subunits of cottonseed catalase. AB - The isolation and sequence of a cDNA encoding a developmentally distinct subunit of cottonseed catalase are presented. A 1.8-kb cDNA was selected from a cDNA library constructed with poly(A)+ RNA isolated from 3-day-old dark-grown cotyledons in which a second subunit (designated SU 2 in an earlier publication) of catalase was predominantly synthesized. The cDNA encodes a 492-amino acid peptide with a calculated Mr of 56,900. The nucleotide sequence is 76% identical to a cDNA encoding another subunit (SU 1) which was predominantly synthesized in 1-day-old-cotyledons. Most of the divergence occurs in the 5' and 3' non-coding regions, and at the third positions of the codons. The deduced amino acid sequence is 92% identical to that of SU 1. Denaturing isoelectric focusing and SDS-PAGE of products transcribed and translated in vitro from these cDNAs revealed that the cDNA selected from the "1-day" library encoded SU 1 and the cDNA selected from the "3-day" library (this paper) encoded SU 2 of catalase. These data and results from Southern blot analyses of genomic DNA indicate that there are two genes encoding catalase subunits in cotton cotyledons, with only one copy of SU 1 and at least two copies of SU 2 in the genome. A peroxisomal targeting signal, e.g., Ser-Lys-Leu, is not located at the C-terminus of either subunit, or within 25 residues of the C-terminus of SU 1, although it occurs at six residues upstream from the C-terminus of SU 2. A possible location of a targeting sequence for catalase and other peroxisomal proteins lacking the C terminal tripeptide motif is proposed. PMID- 1898071 TI - Characterization of the constitutive and wound-inducible monoterpene cyclases of grand fir (Abies grandis). AB - Monoterpene cyclase activity is greatly increased in grand fir (Abies grandis) sapling stems in response to wounding and the composition of the cyclic olefin mixture generated differs from that produced constitutively as determined by radio gas-liquid chromatography. Cell-free extracts from wounded stems and from non-wounded controls were systematically compared for monoterpene cyclase activities following partial purification and separation of these enzymes by anion-exchange chromatography (Mono Q FPLC) and native PAGE. The increase in monoterpene cyclase activity following wounding represents both the apparent enhancement of constitutive cyclase activities and the appearance of novel cyclization enzymes that are absent in nonwounded controls. A pinene cyclase was shown to be the major wound-inducible enzyme directly responsible for oleoresin monoterpene formation and was tentatively identified as a 62-kDa protein by SDS PAGE. PMID- 1898072 TI - Regulation of fatty acid beta-oxidation in rat heart mitochondria. AB - In an attempt to elucidate the mechanism by which the rate of fatty acid oxidation is tuned to the energy demand of the heart, the effects of changing intramitochondrial ratios of [acetyl-CoA]/[CoASH] and [NADH]/[NAD+] on the rate of beta-oxidation were studied. When 10 mM L-carnitine was added to coupled rat heart mitochondria to lower the ratio of [acetyl-CoA]/[CoASH], the rate of palmitoylcarnitine beta-oxidation, as measured by the formation of acid-soluble products, was stimulated more than fourfold at state 4 respiration while beta oxidation at state 3 respiration was hardly affected. Neither oxaloacetate nor acetoacetate, added to mitochondria to lower the [NADH]/[NAD+] ratio, stimulated beta-oxidation. Rates of respiration at states 3 and 4 were unchanged by additions of L-carnitine, oxaloacetate, or acetoacetate. Determinations of intramitochondrial ratios of [acetyl-CoA]/[CoASH] by high performance liquid chromatography yielded values close to 10 for palmitoylcarnitine-supported respiration at state 4 and 2.5 at state 3 respiration. Addition of 10 mM L carnitine caused a dramatic decrease of these ratios to less than 0.2 at both respiration states. Studies with purified or partially purified enzymes revealed strong inhibitions of 3-ketoacyl-CoA thiolase by acetyl-CoA and of L-3 hydroxyacyl-CoA dehydrogenase by NADH. Moreover, the activity of 3-ketoacyl-CoA thiolase at concentrations of acetyl-CoA and CoASH prevailing at state 3 respiration was 4 times higher than its activity in the presence of acetyl-CoA and CoASH observed at state 4. Altogether, this study leads to the conclusion that the rate of beta-oxidation in heart can be regulated by the intramitochondrial ratio of [acetyl-CoA]/[CoASH] which reflects the energy demand of the tissue. The thiolytic cleavage catalyzed by 3-ketoacyl-CoA thiolase may be the site at which beta-oxidation is controlled by the [acetyl-CoA]/[CoASH] ratio. PMID- 1898073 TI - The 43-kDa glycoprotein from the human pathogen Paracoccidioides brasiliensis and its deglycosylated form: excretion and susceptibility to proteolysis. AB - Biochemical properties of the concanavalin A-binding 43-kDa glycoprotein (gp43) of Paracoccidioides brasiliensis and its deglycosylated form were compared. Deglycosylation was achieved by treatment with trifluoromethanesulfonic acid, endoglycosidase H, N-glycanase, or metabolically, by growing cells with tunicamycin. The resulting antigen in all cases had Mr 38,000, and probably derived from the gp43 by loss of N-linked high-mannose oligosaccharide chains. The presence of galactopyranose units in the carbohydrate chains was suggested by antigen binding to peanut lectin. Pulse and chase experiments using [35S]methionine metabolic labeling of P. brasiliensis growing in the presence of tunicamycin showed that the N-linked chains of gp43 are not required for antigen secretion. The 38-kDa antigen was more susceptible than the native antigen to the action of papain and pronase, thus indicating a protective role of the carbohydrate moiety against proteolysis. Both forms are equally resistant to endogenous proteases at neutral pH. The gp43, itself, has a proteolytic activity at pH 5-6, but not at neutral pH. Deglycosylation with endoglycosidase H or tunicamycin preserved epitopes in the 38-kDa molecule reactive with (a) antibodies from patients with paracoccidioidomycosis, or rabbit immunized with the gp43 and (b) mouse monoclonal antibodies against the gp43 antigen. The present results provide a basis for the understanding of diagnostic reactions and fungal virulence involving the gp43 exocellular antigen of P. brasiliensis. PMID- 1898075 TI - Studies of the thermal inactivation of cardiac adenylyl cyclase: evidence for a conformational change in the reaction mechanism. AB - Membrane bound cardiac adenylyl cyclase was shown to undergo a spontaneous and irreversible thermal inactivation with a t1/2 of approximately 10 min. The loss of activity could not be explained by the action of endogenous proteases. Repeated freeze-thaw of membrane preparations resulted in a much increased rate of thermal inactivation (t1/2 = approx. 2 min). ATP, adenylimidodiphosphate, ADP, and PPi protected the enzyme from thermal inactivation with dissociation constants (Kd) of 193, 5.04, 84.4, and 6.3 microM, respectively. 5'-AMP and cyclic AMP were ineffective as protectors at concentrations as high as 3 mM. Activators of adenylyl cyclase such as Mn2+, forskolin, 5 guanylylimidodiphosphate, and NaF and 9 mM Mg2+ protected against thermal inactivation with Kd of 16.8 microM, 8.81 microM, 0.23 microM and 1.04 mM, respectively. Mg2+ alone was without effect. Thermal inactivation was first order under all conditions tested. Arrhenius plots of the rate constants for inactivation vs temperature were linear. The increased stability of ligand bound adenylyl cyclase was shown to be associated with an increased free energy of activation (delta G 0). These data provide evidence for the existence of two distinct conformations of cardiac adenylyl cyclase based on different susceptibilities to thermal inactivation. These enzyme conformations, termed E1 and E2, may be important reaction intermediates. The thermal stability of E1 was highly influenced by the enzyme's membrane lipid environment. The formation of E2 from E1 was enhanced by interaction with substrate, PPi, activators of adenylyl cyclase, and by interaction with dissociated stimulatory guanine nucleotide binding protein-alpha beta gamma heterotrimers. PMID- 1898074 TI - Prevention of nitrofurantoin-induced cytotoxicity in isolated hepatocytes by fructose. AB - Nitrofurantoin is a widely utilized urinary antimicrobial drug which has been associated with pulmonary fibrosis, neuropathy, and hepatitis as well as hemolytic anemia in glucose-6-phosphate dehydrogenase-deficient individuals. Incubation of freshly isolated rat hepatocytes with nitrofurantoin caused oxygen activation as a result of futile redox cycling. Glutathione disulfide (GSSG) was formed and rapidly exported from the cell resulting in complete glutathione (GSH) depletion followed by cell death. However, fructose prevented the export of GSSG from the cell and GSH levels recovered rapidly without cytotoxicity occurring. Fructose did not affect nitrofurantoin metabolism but rapidly depleted cellular ATP levels by approximately 80% which remained depressed during the incubation period. Fructose, however, did not protect hepatocytes from nitrofurantoin induced cytotoxicity if GSH was depleted beforehand. Protection by fructose only occurred at concentrations which caused ATP depletion. These results suggest that fructose prevents nitrofurantoin-induced toxicity by depleting ATP and thereby preventing the ATP-dependent GSSG efflux. GSSG is retained enabling NADPH and glutathione-reductase to reduce the GSSG back to GSH, thereby protecting the cell from nitrofurantoin-induced oxidative stress. PMID- 1898076 TI - Vanadate modulates the activity of a subpopulation of asialoglycoprotein receptors on isolated rat hepatocytes: active surface receptors are internalized and replaced by inactive receptors. AB - In the absence of ligand, sodium vanadate causes a time- and dose-dependent loss of up to approximately 50% of the surface galactosyl receptor (GalR) activity in rat hepatocytes at 37 degrees C. The effect on total (surface plus intracellular) GalR activity is also dependent on exposure time and vanadate concentration. At less than 1 mM, vanadate induces a transient decrease and then partial recovery of cell surface GalR activity. At greater than 3 mM vanadate, surface GalR activity decreases rapidly (t1/2 approximately 2 min). Lost surface activity is initially recovered in digitonin-permeabilized cells, indicating that active surface GalRs redistribute to the cell interior. However, an antibody assay for GalR protein showed that although surface activity decreased, there was no decrease in surface receptor protein. The active intracellular GalRs then slowly inactivate over 30-60 min. With 8 mM vanadate, the loss of both surface and total cellular GalR activity is more rapid and coincident; no lag is observed. Maximal activity loss, however, was still only approximately 50%. Again, no net change was seen in the distribution of GalR protein between the cell surface and the interior. These results indicate that vanadate causes active GalRs to move from the surface to the inside and be replaced by inactive receptors moving from the inside to the cell surface. The Gal receptor system is comprised of two functionally different receptor subpopulations that operate via two distinct intracellular pathways. Only the State 2 GalRs, which recycle constitutively, are sensitive to modulation by vanadate. Consistent with this, vanadate inhibits the endocytosis of 125I-asialoorosomucoid (ASOR) only partially. The rate of uptake and the steady state level of ASOR intracellular accumulation were maximally inhibited by 50 and 70%, respectively, at 0.2 mM vanadate. The rate and extent of degradation of 125I-ASOR were also inhibited by 50-70%. Residual ASOR uptake and degradation is accounted for by the minor vanadate-resistant State 1 Gal receptor pathway. PMID- 1898077 TI - Regulation of C4 photosynthesis: modulation of mitochondrial NAD-malic enzyme by adenylates. AB - Effects of adenylates on the activity of mitochondrial NAD-malic enzyme from NAD malic-enzyme (NAD-ME)-type and phosphoenolpyruvate-carboxykinase-(PKC)-type C4 plants are examined. At physiological concentrations, ATP, ADP, and AMP all inhibit the enzyme from Atriplex spongiosa and Panicum miliaceum (NAD-ME-type plants), with ATP the most inhibitory species. The degree of inhibition is greater with subsaturating levels of activator, malate, and Mn2+. NAD-malic enzyme from Urochloa panicoides (PCK-type) is activated by ATP (up to 10-fold) and inhibited by ADP and AMP. These effects are discussed in relation to regulation of C4 photosynthesis. PMID- 1898078 TI - Heme regulates hepatic 5-aminolevulinate synthase mRNA expression by decreasing mRNA half-life and not by altering its rate of transcription. AB - Hepatic 5-aminolevulinate (ALA) synthase, the first and rate-limiting enzyme in the heme biosynthetic pathway, is known to be feedback repressed by the end product of the pathway, heme. We investigated whether heme regulates ALA synthase mRNA expression transcriptionally or post-transcriptionally in primary cultures of chick embryo hepatocytes. 2-Propyl-2-isopropylacetamide increased the rate of transcription of the ALA synthase gene, whereas heme or an inhibitor of heme biosynthesis, desferrioximine, had no effect on the drug-induced transcription rate. Heme decreased the half-life of ALA synthase mRNA from approximately 3.5 h to 1.2 as recently reported by Drew and Ades (1989, Biochem. Biophys. Res. Commun. 162, 102-107). We also found that the heme-mediated decrease in mRNA stability was prevented by cycloheximide treatment, suggesting that the heme effect was mediated by a labile protein. These results support a model for hepatic ALA synthase regulation in which inducing drugs directly stimulate ALA synthase gene transcription, whereas heme regulates ALA synthase expression post transcriptionally by modulating mRNA stability as well as by blocking translocation of ALA synthase enzyme into the mitochondrion. PMID- 1898079 TI - Temperature-induced changes in the flexibility of the loop between SH1 (Cys-707) and SH3 (Cys-522) in myosin subfragment 1 detected by cross-linking. AB - The ability of dibromobimane to cross-link SH1 (Cys-707) in the 21-kDa C-terminal segment to SH3 (Cys-522) in the 50-kDa middle segment of the myosin S1 heavy chain has been examined as a function of nucleotide binding and temperature. The results obtained indicate that, while the reagent rapidly reacts with SH1 at both 25 and 4 degrees C, its ability to cross-link to SH3 is highly dependent on temperature. At 25 degrees C, substantial cross-linking from monofunctionally labeled SH1 to SH3 occurs, in agreement with recent work of Mornet, Ue, and Morales (1985, Proc. Natl. Acad. Sci, USA 82, 1658-1662) and of Ue (1987, Biochemistry 26, 1889-1894) and with their conclusion that a loop, allowing SH1 and SH3 to reside at the cross-linking span of dibromobimane, preexists in the protein. At 4 degrees C, however, negligible amounts of cross-linking are observed whether or not a nucleotide is present, despite indications that SH1 is labeled rapidly by the reagent at this temperature. The inability to form this cross-link is not due to an alternate cross-link between monofunctionally labeled SH1 and another thiol in the 21-kDa segment. These results indicate that this loop exists at 25 degrees C and does not exist (or exists only transiently) at the lower temperature. PMID- 1898080 TI - Multiple forms of liver microsomal flavin-containing monooxygenases: complete covalent structure of form 2. AB - Hepatic flavin-containing monooxygenases catalyze NADPH-dependent oxygenation of a wide variety of drugs that possess a nucleophilic heteroatom. Two forms of these enzymes (form 1 and 2) have been isolated from rabbit liver microsomes and partially characterized (Ozols, J., 1989, Biochem. Biophys. Res. Commun. 163, 49 55). The complete amino acid sequence of form 2 is presented here. Sequence determination was achieved by pulsed liquid-phase and solid-phase sequencing of 40 peptides generated by chemical and enzymatic cleavages, including CNBr cleavage of tryptophanyl residues. Form 2 monooxygenase contains 533 amino acid residues and has a molecular weight of 60,089. The COOH terminus of this enzyme is very hydrophobic and presumably functions to anchor the protein to the membrane. Form 2 is readily degraded, since a form lacking residues 1 to 278 and a form without the COOH-terminal segment were also isolated from solubilized membrane preparations. The amino acid sequence of form 2 is 52% identical to that of form 1 and shows 55% identity to the sequence of rabbit lung monooxygenase derived from the cDNA data. The putative FAD and NADP binding segments around residues 9 and 190 are conserved in all three forms. Three variable segments can also be identified in these isoforms. These are residues 308 to 321, residues 408 to 421, and the membrane binding domain, residues 505 to 533. A comparison of the presently limited amino acid sequence data of flavin-containing monooxygenases (FMOs) implies that a particular FMO in different mammalian species may be very similar, but isozymes within a species may exhibit more extensive variability with respect to homology and catalytic activity. This study documents the structural diversity of a second hepatic FMO from rabbit liver and establishes this class of drug-metabolizing enzymes as a family of related proteins. PMID- 1898081 TI - Human surfactant protein D: SP-D contains a C-type lectin carbohydrate recognition domain. AB - Lung surfactant protein D (SP-D) shows calcium-dependent binding to specific saccharides, and is similar in domain structure to certain members of the calcium dependent (C-type) lectin family. Using a degenerate oligomeric probe corresponding to a conserved peptide sequence derived from the amino-terminus of the putative carbohydrate binding domain of rat and bovine SP-D, we screened a human lung cDNA library and isolated a 1.4-kb cDNA for the human protein. The relationship of the cDNA to SP-D was established by several techniques including amino-terminal microsequencing of SP-D-derived peptides, and immunoprecipitation of translation products of transcribed mRNA with monospecific antibodies to SP-D. In addition, antibodies to a synthetic peptide derived from a predicted unique epitope within the carbohydrate recognition domain of SP-D specifically reacted with SP-D. DNA sequencing demonstrated a noncollagenous carboxy-terminal domain that is highly homologous with the carboxy-terminal globular domain of previously described C-type lectins. This domain contains all of the so-called "invariant residues," including four conserved cysteine residues, and shows high homology with the mannose-binding subfamily of C-type lectins. Sequencing also demonstrated an amino-terminal collagenous domain that contains an uninterrupted sequence of 59 Gly-X-Y triplets and that also contains the only identified consensus for asparagine-linked oligosaccharides. The studies demonstrate that SP D is a member of the C-type lectin family, and confirm predicted structural similarities to conglutinin, SP-D, and the serum mannose binding proteins. PMID- 1898082 TI - Regulation of collagen synthesis by ascorbic acid: characterization of the role of ascorbate-stimulated lipid peroxidation. AB - Recently, we have described the ability of traditional lipid peroxidation inhibitors to inhibit ascorbate-stimulated collagen synthesis. In order to characterize further this effect, we have tested the ability of known and potential inhibitors of lipid peroxidation for their effects on ascorbate stimulated collagen synthesis and lipid peroxidation. In our experiments, mannitol, a water soluble antioxidant, had no effect on ascorbate-induced collagen synthesis nor on lipid peroxidation. However, alpha-tocopherol, which is a lipophilic antioxidant, inhibited both effects of ascorbate. Superoxide dismutase, catalase, and their polyethylene glycol conjugate forms did not inhibit the ascorbate-stimulated collagen synthesis or lipid peroxidation. In addition, no effect was seen with the oxygen radical scavengers isopropanol, ethanol, or dimethyl sulfoxide. Two iron chelators, o-phenanthroline and alpha,alpha-dipyridyl, both inhibited ascorbate-induced lipid peroxidation and collagen synthesis, consistent with the previously described iron-dependence of lipid peroxidation by ascorbate. These results support a correlation between collagen synthesis and lipid peroxidation and provide a theory for the mechanism of ascorbic acid regulation of collagen synthesis. PMID- 1898083 TI - Thermal denaturation profiles of deoxypolynucleotide-destabilizer ligand complexes: semiempirical studies. AB - In this paper, we study the dependence of the Tm (melting temperature) of complexes formed between double-stranded deoxypolynucleotides and pure destabilizer nonspecific ligands on Kc (intrinsic association constant), nc (apparent site size), and wc (cooperativity constant). Using the Sequence Generating Function (SGF) method, we have found a simple, analytical relationship between the Tm and these interaction parameters. The validity of this relationship depends strongly on the sigma value (sigma being the nucleation parameter of the deoxypolynucleotide). Through the equation so obtained, it is possible to evaluate Kc, nc, and wc from the melting temperature of three experimental thermal denaturation profiles at different r (ligand/deoxypolynucleotide ratio) values. However, when wc greater than 100, a degeneration in the wc and Kc values appears, and the study of the free deoxypolynucleotide region in the melting profile is necessary in order to accurately evaluate these two parameters. The method has been checked using complexes formed with poly(d(A-T].poly(d(A-T] and both bovine pancreatic ribonuclease and protein GP32 of phage T4 as experimental models. The applicability of the method here developed is discussed in relation to the nature of the ligands and the sigma and wc values. PMID- 1898084 TI - The interaction of cardiolipin with rat liver carbamoyl phosphate synthetase I. AB - A selective interaction of rat liver carbamoyl phosphate synthetase I with cardiolipin, and other anionic phospholipids, has been demonstrated. The enzymatic activity of the synthetase is inhibited by cardiolipin and, to a lesser extent, by phosphatidylglycerol, phosphatidylinositol, and phosphatidylserine. This group of anionic phospholipids also induced a conformational change in the synthetase, yielding a species with increased exposure of the linkages between independently folded domains of the enzyme, as determined by limited proteolysis under nondenaturing conditions. The interaction of cardiolipin with carbamoyl phosphate synthetase I was a fairly slow process, with complex kinetics, and was apparently irreversible. The inclusion of Mg2+ or of MgATP in the incubation mixture prevented the cardiolipin effects. The zwitterionic phospholipids phosphatidylcholine and phosphatidylethanolamine had negligible effects on the structure and activity of the synthetase. This interaction between cardiolipin and carbamoyl phosphate synthetase I potentially constitutes one of the mechanisms by which the synthetase forms its loose association with the inner mitochondrial membrane. Multiple mechanisms, including synthetase conformational changes, cardiolipin phase changes, and ATP/ADP binding site involvement, are possibly involved in the phospholipid/synthetase interaction and the resulting potential regulatory mechanism(s) for urea cycle activity. PMID- 1898086 TI - Steroid hormone hydroxylase specificities of eleven cDNA-expressed human cytochrome P450s. AB - Steroid hydroxylation specificities were determined for 11 forms of human cytochrome P450, representing four gene families and eight subfamilies, that were synthesized in human hepatoma Hep G2 cells by means of cDNA-directed expression using vaccinia virus. Microsomes isolated from the P450-expressing Hep G2 cells were isolated and then assayed for their regioselectivity of hydroxylation toward testosterone, androstenedione, and progesterone. Four of the eleven P450s exhibited high steroid hydroxylase activity (150-900 pmol hydroxysteroid/min/mg Hep G2 microsomal protein), one was moderately active (30-50 pmol/min/mg) and six were inactive. In contrast, 10 of the P450s effectively catalyzed O-deethylation of 7-ethoxycoumarin, a model drug substrate, while only one (P450 2A6) catalyzed significant coumarin 7-hydroxylation. Human P450 4B1, which is expressed in lung but not liver, catalyzed the 6 beta-hydroxylation of all three steroids at similar rates and with only minor formation of other hydroxylated products. Three members of human P450 family 3A, which are expressed in liver and other tissues, also catalyzed steroid 6 beta-hydroxylation as their major activity but, additionally, formed several minor products that include 2 beta-hydroxy and 15 beta-hydroxy derivatives in the case of testosterone. These patterns are similar to those exhibited by rat family 3A P450s. Although several rodent P450s belonging to subfamilies 2A, 2B, 2C, 2D are active steroid hydroxylases, four of five human P450s belonging to these subfamilies exhibited very low activity or were inactive, as were the human 1A and 2E P450s examined in the present study. These studies demonstrate that individual human cytochrome P450 enzymes can hydroxylate endogenous steroid hormones with a high degree of stereospecificity and regioselectivity, and that some, but not all of the human cytochromes exhibit metabolite profiles similar to their rodent counterparts. PMID- 1898085 TI - Stable ornithine decarboxylase in a rat hepatoma cell line selected for resistance to alpha-difluoromethylornithine. AB - Ornithine decarboxylase (ODC) is extremely unstable in mammalian cells. This unusual characteristic facilitates rapid fluctuations in the activity of this enzyme in response to variations in its biosynthesis. Unfortunately, very little is known about the mechanism or regulation of this ODC-specific proteolytic pathway. This study describes the production and characterization of a variant of the rat hepatoma HTC cell line that is strikingly deficient in this pathway. This cell variant was induced by selection for growth in stepwise increasing concentrations (up to 10 mM) of the irreversible ODC inhibitor, alpha difluoromethylornithine (DFMO). Resistance to this inhibitor appears to result from a combination of elevated (10X) ODC biosynthesis and inhibited degradation, producing greater than a 2000-fold increase in the level of ODC protein. In these variant cells (DH23b) inhibition of protein synthesis by cycloheximide did not result in rapid loss of enzyme activity or ODC protein determined by radioimmunoassay. Pulse-chase studies with [35S]methionine confirmed that this enzyme was not preferentially degraded, even when spermidine was added to the media. ODC purified from the variant cells was found to be identical to the control cell enzyme in size, isoelectric point, substrate binding kinetics, and sensitivity to the inhibitor DFMO. Also, as in the control cells, a major fraction of the ODC molecules extracted from DH23b cells was shown to be phosphorylated on a serine residue. The inability to detect physical or kinetic differences between the parent and the variant cell ODC suggests that the unusual stability of ODC in this cell is associated with a defect in a cellular mechanism for ODC-specific degradation. PMID- 1898088 TI - Analysis of subsite preferences of HIV-1 proteinase using MA/CA junction peptides substituted at the P3-P1' positions. AB - The residues P3, P2, P1, and P1' of a peptide corresponding to the matrix/capsid protein junction in the HIV-1 gag protein (Ser-Gln-Asn-Tyr-Pro-Ile-Val) were systematically replaced and the effect of these single amino acid substitutions on the hydrolysis of each peptide by HIV-1 proteinase was studied. Subsites S1 and S1' of the enzyme showed explicit preference for hydrophobic moieties, but beta-branched amino acids and proline are not tolerated in S1. The S2 subsite shows a preference for small polar and apolar amino acids; it may be occupied by Asn, Asp, Glu, Cys, Ala, or Val, other substitutions, especially by Gln and Ser, prevent hydrolysis of the peptides. In subsite S3 all amino acids except proline can be accommodated. PMID- 1898087 TI - Involvement of heme in the transcriptional activation of CYPIIB1/B2 gene by phenobarbitone in rat liver--studies with succinylacetone. AB - Earlier studies in this laboratory had implicated heme to function as a positive modulator of phenobarbitone-mediated activation of CYPIIB1/B2 gene transcription in rat liver. However, recent reports have indicated that succinylacetone, a specific inhibitor of delta-aminolevulinate dehydrase, does not affect this process. The present studies indicate that succinylacetone does inhibit the phenobarbitone-mediated increase in CYPIIB1/B2 mRNAs and their transcription in rat liver at early time points (45 min to 3 h), but the inhibition is not pronounced at later time points (16 h). Succinylacetone is a weaker inhibitor of heme biosynthesis than CoCl2, 3-amino-1,2,4-triazole, or thioacetamide used earlier in this laboratory. Succinylacetone induces delta-aminolevulinate synthase, whereas the other compounds depress the levels of the enzyme. There is a good correlation between the amount of freshly synthesized nuclear heme pool and the activation of CYPIIB1/B2 transcription by phenobarbitone. A model implicating a nuclear heme pool regulating the transcription of delta aminolevulinate synthase, CYPIIB1/B2, and heme oxygenase genes is proposed. PMID- 1898089 TI - Rat liver mitochondrial malate dehydrogenase: purification, kinetic properties, and role in ethanol metabolism. AB - Malate dehydrogenase was purified from the mitochondrial fraction of rat liver by ion-exchange chromatography with affinity elution. The kinetic parameters for the enzyme were determined at pH 7.4 and 37 degrees C, yielding the following values (microM): Ka, 72; Kia, 11; Kb, 110; Kp, 1600; Kip, 7100; Kq, 170; Kiq, 1100, where a = NADH, b = oxalacetate, p = malate, and q = NAD+. Kib was estimated to be about 100 microM. The maximum velocities for mitochondrial malate dehydrogenase in rat liver homogenates, at pH 7.4 and 37 degrees C, were 380 +/- 40 mumol/min per gram of liver, wet weight, for oxalacetate reduction and 39 +/- 3 mumol/min per gram of liver, wet weight, for malate oxidation. Rates of the reaction catalyzed by mitochondrial malate dehydrogenase under conditions similar to those in vivo were calculated using these kinetic parameters and were much lower than the maximum velocity of the enzyme. Since mitochondrial malate dehydrogenase is not saturated with malate at physiological concentrations, its kinetic parameters are probably important in the regulation of mitochondrial malate concentration during ethanol metabolism. For the mitochondrial enzyme to operate at a rate comparable to the flux through cytosolic malate dehydrogenase during ethanol metabolism (about 4 mumol min-1 per gram liver), the mitochondrial [malate] would need to be about 2 mM and the mitochondrial [oxalacetate] would need to be less than 1 microM. PMID- 1898090 TI - Electron microscopic localization of pyruvate carboxylase in rat liver and Saccharomyces cerevisiae by immunogold procedures. AB - The intracellular location of pyruvate carboxylase (EC 6.4.1.1) in rat liver and Saccharomyces cerevisiae was investigated using the antibody-gold and protein A gold techniques carried out as a postembedding immunoelectron microscopic procedure. The vast majority of gold particles (greater than 98%), indicative of the presence of antigenic sites of pyruvate carboxylase, were found in the mitochondria of rat liver. No other cellular compartment was labeled except the cytosol which did not account for more than 2% of the total labeling of a rat hepatocyte. Furthermore, 60% of labeled pyruvate carboxylase molecules within a mitochondrion were found adjacent to the matrix side of the inner mitochondrial membrane. In contrast, in S. cerevisiae, pyruvate carboxylase was found exclusively in the cytosol. PMID- 1898091 TI - Interaction of copper-metallothionein from the American lobster, Homarus americanus, with glutathione. AB - Organisms have harnessed the unique chemistry of copper for a variety of purposes. However, that same chemistry makes this essential metal toxic at elevated concentrations. Metallothioneins (MTs), a family of small metal-binding proteins, are thought to play a crucial role in the regulation of this reactive ion. Here we report that copper-metallothioneins from the American lobster, Homarus americanus, interact with the tripeptide glutathione (gamma-Glu-Cys-Gly). Glutathione in the cytosolic fraction prepared from the digestive gland of the American lobster coelutes with copper-metallothionein during size-exclusion chromatography. The latter protein can be separated into three isoforms by anion exchange chromatography. All three isoforms belong to the class I MTs. CuMT-I and -II are very similar, whereas CuMT-III is distinct from isoforms I and II. The interaction between glutathione and MT isoforms was examined by ultrafiltration experiments and size-exclusion HPLC. CuMT-III forms a stable 1:1 complex with glutathione, with a dissociation constant of 1 microM. CuMT-I/II makes a transient complex with glutathione, which releases copper as a copper-glutathione complex. This complex can function as the source of Cu(I) in the restoration of the oxygen-binding capacity of copper-free hemocyanin. These studies suggest that metallothionein and glutathione are intricately linked in the biochemistry of copper regulation. PMID- 1898092 TI - The effect of ligand binding on the proteolytic pattern of methylmalonate semialdehyde dehydrogenase. AB - Native rat liver methylmalonate semialdehyde dehydrogenase was proteolyzed by lysylendopeptidase C, chymotrypsin, and trypsin to generate different cleavage fragments of molecular masses: 50, 8, 55, 44, 39, 53, 45, and 40 kDa. A proteolytic cleavage map of MMSDH was constructed based on sequencing data and a comparison of appearance and degradation rates of the different protein fragments as shown by SDS-PAGE. NAD+ was highly effective as a protector against proteolysis in both the N-terminal and the C-terminal parts of the intact enzyme. NADH did not efficiently protect the intact enzyme; however, it stabilized proteolytic fragment L50 from further degradation. This suggests that the NAD(+) binding domain is not destroyed by cleavage of the N-terminal part of MMSDH. CoA had no effect on the proteolytic cleavage patterns of MMSDH. However, CoA esters reduced the protective effect of NAD+ with an order of effectiveness of acetyl CoA greater than propionyl-CoA greater than butyryl-CoA. p-Nitrophenyl acetate, substrate for esterase activity by the enzyme, partially prevented the protective effect of NAD+ against proteolysis. These results suggest that S-acylation of the enzyme prevents a stabilizing conformational change induced in MMSDH by NAD+ binding. PMID- 1898093 TI - Thermotropic properties of dispersions of cholesterol with tetraether lipids from Thermoplasma acidophilum. AB - The main glycophospholipid from Thermoplasma acidophilum is composed of a diisopranol-2,3-glycerotetraether. The fraction of pentane cyclizations of its hydrocarbon chains increases with the growth temperature of the source organism (39-59 degrees C). Hydrated mixtures of these lipids together with cholesterol have been studied by calorimetry. With the reduction of the phase transition temperatures and enthalpy changes of the transitions, cholesterol is readily incorporated into lipid monolayers in the liquid-crystalline and the (metastable) solid-analogue phase. Lipid samples with a high number of acyclic hydrocarbon chains form a stable and a metastable solid-analogue phase. With the increasing concentration of cholesterol the metastable solid-analogue phase is stabilized and the time constant for the formation of the stable solid-analogue phase is prolonged. PMID- 1898094 TI - An elastolytic proteinase from rabbit leukocytes: purification and partial characterization. AB - A proteinase with elastolytic activity was isolated from granules of rabbit bloodstream leukocytes, and purified to apparent homogeneity by a multi-step procedure consisting of ammonium sulfate precipitation, batch fractionation on DEAE-Sephadex A-50, and finally by preparative isoelectric focusing (IEF) on Sephadex G-75 Superfine. The molecule weight of the enzyme, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), was 28,500. This enzyme shows an isoelectric point at pH 9.0. The proteinase is active against natural elastins as well as toward Suc-(Ala)3-NA, Methoxy-Suc-(Ala)2-Pro Val-NA, and (to a lesser extent) against Suc-(Ala)2-Pro-Leu-NA and Boc-Ala-ONp. The inhibition profile of the isolated enzyme indicates that rabbit granulocyte elastase belongs to the group of serine proteinases. Inhibition by some natural proteinase inhibitors is also observed. Unlike other mammalian elastases, it is insensitive to elastatinal. PMID- 1898095 TI - Interdependence of ryanodine binding, oligomeric receptor interactions, and Ca2+ release regulation in junctional sarcoplasmic reticulum. AB - We have examined ryanodine binding to its receptor (RR) and compared its effect on Ca2+ release to the Ca2+ release triggered by Ca2+ plus ATP, using vesicular fragments of junctional terminal cisternae (JTC) obtained from skeletal muscle. Ryanodine binding is slow (taking hours or days to complete) and is highly temperature (Q10 = 4) and Ca2+ dependent. At equilibrium, the extent of binding increases as the concentration of ryanodine is raised above 10(-9) M, exhibiting negative cooperativity and reaching the stoichiometry of the 560,000-Da RR chains near 10(-5) M ryanodine. The specificity of the high affinity binding is demonstrated by competitive binding of ryanodine analogs. Kinetic studies using rapid filtration show that, in the absence of ryanodine, rapid (k = 15 s-1) release of Ca2+ follows a triggering exposure of loaded JTC vesicles to perfusion media containing Ca2+ plus ATP. Induction of this release has no lag period and displays minimal temperature dependence. In contrast, prolonged exposure of JTC vesicles to low (10(-7) M) ryanodine concentrations changes the JTC to a state permitting slow (k = 1 s-1) release of Ca2+ even in the absence of the Ca2+ plus ATP trigger. Higher (greater than microM) concentrations of ryanodine do not allow any Ca2+ release and prevent even the release normally triggered by Ca2+ plus ATP. Our data suggest that ryanodine binds to the open state of the tetrameric RR, inducing protein conformational changes and altered oligomeric interactions. Binding of the first molecule of ryanodine to one of the four binding sites on the receptor produces a partially closed and low conductance state of the Ca2+ release channel and reduces the ryanodine binding affinity of the remaining sites. Ryanodine occupancy of all four binding sites on the receptor completes closure of the Ca2+ channel and blocks the triggering action of Ca2+ plus ATP. The tetrameric association of the RR chains is demonstrated by crosslinking with bifunctional reagents, generating crosslinked tetramers that retain ryanodine binding and Ca2+ release functions. PMID- 1898096 TI - gp160 of HIV-I synthesized by persistently infected Molt-3 cells is terminally glycosylated: evidence that cleavage of gp160 occurs subsequent to oligosaccharide processing. AB - The envelope glycoprotein of HIV-I in infected, cultured human T cells is synthesized as a precursor of apparent Mr 160 kDa (gp160) and is cleaved to two glycoproteins, gp120 and gp41, which are the mature envelope glycoproteins in the virus. Neither the temporal and spatial features of glycosylation nor the oligosaccharide processing and proteolytic cleavage of the envelope glycoprotein are well understood. To understand more about these events, we investigated the glycosylation and cleavage of the envelope glycoproteins in the CD4+ human cell line, Molt-3, persistently infected with HIV-I (HTLV IIIB). The carbohydrate analysis of gp160 and gp120 and the behavior of the glycoproteins and glycopeptides derived from them on immobilized lectins demonstrate that both of these glycoproteins contain complex- and high-mannose-type Asn-linked oligosaccharides. In addition, the N-glycanase-resistant oligosaccharides of gp120 were found to contain N-acetyl-galactosamine, a common constituent of Ser/Thr-linked oligosaccharides. Pulse-chase analysis of the conversion of [35S]cysteine-labeled gp160 showed that in Molt-3 cells it takes about 2 h for gp120 to arise with a half-time of conversion of about 5 h. At its earliest detectable occurrence, gp120 was found to contain complex-type Asn-linked oligosaccharides. Taken together, these results indicate that proteolytic cleavage of gp160 to gp120 and gp41 occurs either within the trans-Golgi or in a distal compartment. PMID- 1898097 TI - Developmental induction, purification, and further characterization of 12:0-ACP thioesterase from immature cotyledons of Umbellularia californica. AB - The fatty acyl content of developing cotyledons of Umbellularia californica (California Bay) changes from a long-chain composition to a predominance of 10:0 and 12:0 in just 4-5 days at the beginning of an approximately 100-day period of medium-chain deposition. This striking change occurs at the earliest appearance of 12:0-acyl-carrier protein (ACP) thioesterase activity. The coincidence of these rapid events is consistent with the hypothesis that the enzyme plays a major role in medium-chain biosynthesis. The 12:0-ACP thioesterase has been substantially purified; enzyme activity consistently comigrates in chromatographic and electrophoretic systems with a protein or pair of proteins having an apparent molecular weight of approximately 34 kDa. A native molecular weight of approximately 42 kDa has been estimated by gel filtration chromatography, suggesting that the enzyme is a monomer. Affinity chromatography on immobilized ACP is a critical step in the purification procedure, and resolves the 12:0-ACP and 18:1-ACP thioesterases sufficiently to confirm that the medium chain enzyme has negligible action on 18:1-ACP. PMID- 1898098 TI - The C-S lyases of higher plants: homogeneous beta-cystathionase of spinach leaves. AB - S-Substituted cysteines and their derivatives are prominent secondary amino acids in a number of plant families. The substituents are often specific and unique to each family. Cystathionine, however, is an ubiquitous S-substituted cysteine found in all autotrophic plants since it is an intermediate in the biosynthesis of methionine. beta-Cystathionase will produce homocysteine and pyruvate from cystathionine by a beta-elimination reaction. The present report describes the purification of this enzyme to homogeneity from spinach leaves and some of its properties. The enzyme has a molecular weight of 210,000 and consists of four identical subunits of Mr 53,000. It has a pH optimum for activity of 8.6-8.7 and utilizes pyridoxal-5'-phosphate as a cofactor. Its specificity is limited to L cystathionine, L-djenkolate, and L-cystine as substrates with a relative activity of 100:126:17, respectively. It is not a glycoprotein unlike a number of previously described plant C-S lyases. PMID- 1898099 TI - Calcium- and phosphate-dependent release and loading of glutathione by liver mitochondria. AB - The status of glutathione (GSH) was studied in isolated rat liver mitochondria under conditions which induce a permeability transition. This transition, which is inhibited by cyclosporin A (CyA), requires the presence of Ca2+ and an inducing agent such as near physiological levels (3 mM) of inorganic phosphate (Pi). The transition is characterized by an increased inner membrane permeability to some low molecular weight solutes and by large amplitude swelling under some experimental conditions. Addition of 70 microM Ca2+ and 3 mM Pi to mitochondria resulted in mitochondrial swelling and extensive release of GSH that was recovered in the extramitochondrial medium as GSH. Both swelling and the efflux of mitochondrial GSH were prevented by CyA. Incubation of mitochondria in the presence of Ca2+, Pi, and GSH followed by addition of CyA provided a mechanism to load mitochondria with exogenous GSH that was greater than the rate of uptake by untreated mitochondria. Thus, GSH efflux from mitochondria may occur under toxicological and pathological conditions in which mitochondria are exposed to elevated Ca2+ in the presence of near physiological concentrations of Pi through a nonspecific pore. Cyclical opening and closing of the pore could also provide a mechanism for uptake of GSH by mitochondria. PMID- 1898100 TI - Initiation of lipid peroxidation in submitochondrial particles: effect of respiratory inhibitors. AB - Initiation of lipid peroxidation in the inner mitochondrial membrane was investigated using respiratory substrates and inhibitors and various iron chelates. An iron chelate was required for initiation of lipid peroxidation in the presence of either NADH or NADPH. The two nicotinamide nucleotides exhibited different activities in initiating lipid peroxidation with regard to concentration and to the effects of rotenone and rhein. Succinate and both nicotinamide nucleotides supported lipid peroxidation in the presence of thenoyl trifluoroacetone (TTFA), without a requirement for exogenously added iron. ADP stimulated lipid peroxidation in the case of NAD(P)H and TTFA, but inhibited it in the case of succinate and TTFA. Lipid peroxidation is thought to be enzymatically induced in both the NADH and the succinate dehydrogenase regions of the respiratory chain, and evidence is presented for a novel pathway of NADPH oxidation that may also be involved. Possible initiation mechanisms are discussed. PMID- 1898101 TI - ATP sulfurylase from trophosome tissue of Riftia pachyptila (hydrothermal vent tube worm). AB - ATP sulfurylase (ATP: sulfate adenylyltransferase, EC 2.7.7.4) was extensively purified from trophosome tissue of Riftia pachyptila, a tube worm that thrives in deep ocean hydrothermal vent communities. The enzyme is probably derived from the sulfide-oxidizing bacteria that densely colonize the tissue. Glycerol (20% v/v) protected the enzyme against inactivation during purification and storage. The native enzyme appears to be a dimer (MW 90 kDa +/- 10%) composed of identical size subunits (MW 48 kDa +/- 5%). At pH 8.0, 30 degrees C, the specific activities (units x mg protein-1) of the most highly purified sample are as follows: ATP synthesis, 370; APS synthesis, 23; molybdolysis, 65; APSe synthesis or selenolysis, 1.9. The Km values for APS and PPi at 5 mM Mg2+ are 6.3 and 14 microM, respectively. In the APS synthesis direction, the Km values for MgATP and SO4(2-) are 1.7 and 27 mM, respectively. The Km values for MgATP and MoO4(2-) in the molybdolysis reaction are 80 and 150 microM, respectively. The Kia for MgATP is 0.65 mM. APS is a potent inhibitor of molybdolysis, competitive with both MgATP and MoO4(2-) (Kiq = 2.2 microM). However, PPi (+ Mg2+) is virtually inactive as a molybdolysis inhibitor. Oxyanion dead end inhibitors competitive with SO4(2-) include (in order of decreasing potency) ClO4- greater than FSO3- (Ki = 22 microM) greater than ClO3- greater than NO3- greater than S2O3(2-) (Ki's = 5 and 43 mM). FSO3- is uncompetitive with MgATP, but S2O3(2-) is noncompetitive. Each subunit contains two free SH groups, at least one of which is functionally essential. ATP, MgATP, SO4(2-), MoO4(2-), and APS each protect against inactivation by excess 5,5'-dithiobis-(2-nitrobenzoate). FSO3- is ineffective as a protector unless MgATP is present. PPi (+Mg2+) does not protect against inactivation. Riftia trophosome contains little or no "ADP sulfurylase." The high trophosome level of ATP sulfurylase (67-176 ATP synthesis units x g fresh wt tissue-1 from four different specimens, corresponding to 4-10 microM enzyme sites), the high kcat of the enzyme for ATP synthesis (296 s-1), and the high Km's for MgATP and SO4(2-) are consistent with a role in ATP formation during sulfide oxidation, i.e., the physiological reaction is APS + MgPPi in equilibrium SO4(2-) + MgATP. PMID- 1898102 TI - Solubilization and properties of GDP-fucose: xyloglucan 1,2-alpha-L fucosyltransferase from pea epicotyl membranes. AB - GDP-fucose:xyloglucan 1,2-alpha-L-fucosyltransferase from pea (Pisum sativum) epicotyl microsomal membranes was readily solubilized by extraction with the zwitterionic detergent 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (Chaps). When using GDP-[14C]fucose as fucosyl donor and tamarind xyloglucan (XG) as acceptor, maximum activation was observed at 0.3% (w/v) Chaps and the highest yield of solubilized activity at 0.4%. The reaction product was hydrolyzed by Trichoderma cellulase to yield labeled oligosaccharides that peaked on gel permeation chromatography at the same elution volume as pea XG nona- and decasaccharide subunits. The apparent Km for fucosyl transfer to tamarind XG by the membrane-bound or solubilized enzyme was about 80 microM GDP-fucose. This was 10 times the apparent Km for fucosyl transfer to endogenous pea nascent XG. Optimum activity was between pH 6 and 7, and the isoelectric point was close to pH 4.8. The solubilized enzyme showed no requirement for, or stimulation by, added cations or phospholipids, and was stable for several months at -70 degrees C. Solubilization and gel permeation chromatography on columns of Sepharose CL-6B enriched the specific activity of the enzyme by about 20-fold relative to microsomes. Activity fractionated on columns of CL-6B with an apparent molecular weight of 150 kDa. The solubilized fucosyltransferase was electrophoresed on nondenaturing polyacrylamide slab gels containing 0.02% (w/v) tamarind XG, and its activity located by incubation in GDP-[14C]fucose, washing, and autoradiographing the gel. A single band of labeled reaction product appeared with an apparent molecular weight of 150 kDa. PMID- 1898103 TI - The native alpha 2 beta 2 tetramer is the only subunit structure of the insulin receptor in intact cells and purified receptor preparations. AB - The native subunit structure of the insulin receptor was reinvestigated by two dimensional nonreducing/reducing gel electrophoresis. Human insulin receptor expressed in murine fibroblasts was found to be a single oligomer, the alpha 2 beta 2 heterotetramer. The structure was assessed using receptor metabolically labeled with [35S]methionine, and using receptor autophosphorylation at two levels of purification: the insulin affinity-purified receptor and the more commonly used wheat germ agglutinin-Sepharose-enriched fraction from whole membrane extracts. Lower molecular weight oligomers and free subunits were observed only upon heating the sample prior to electrophoresis. This artifact of sample handling was dependent upon three factors: (i) temperature, (ii) time of heating, and (iii) impurities typically present in partially purified receptor preparations. We conclude that the alpha 2 beta 2 tetramer is the only insulin receptor subunit structure native in intact cells and subsequently isolated from cell membranes. PMID- 1898105 TI - Studies of crystallization conditions for native and subtilisin-cleaved pig brain tubulin. AB - A survey of crystallization conditions for pig brain tubulin, using standard vapor diffusion techniques in sitting drops or capillaries, has resulted in irregular, fragile needles or plates with a largest dimension of 0.5 mm. These occurred in 2.5% PEG (MW 3350), 0.1 M Pipes, pH 6.2 and 6.4, 2-16 mM MgSO4, 10-15 mM DTE, and 0.1 mM GDP at 8 degrees C. When GTP replaced GDP these aggregates did not form under any of the conditions surveyed (temperature: 8-10 degrees C; MgSO4: 2-16 mM; pH 6-7; PEG, MW 3350: 1.25-12.5%). EM observations demonstrated that sheets of rings appear in crystal solutions in the presence of GDP or GTP. These results are consistent with the results of Howard and Timasheff (1986, Biochemistry 25, 8292-8300) that tubulin rings form in the presence of GDP or GTP but more readily in GDP. Tubulin crystallization experiments are hampered by tubulin's high degree of heterogeneity. Much of the variability lies in the carboxyl terminal region. Conditions for limited digestion of the heterodimer by subtilisin, removing only the carboxyl terminus, were determined. Reduction of heterogeneity was demonstrated by isoelectric focusing. The solubilities of native and subtilisin-cleaved tubulin in MgSO4, (NH4)2SO4, PEG (MW 1450, 3350, 10,000), DMSO, and MPD were compared. Subtilisin-cleaved tubulin precipitated more readily than native tubulin under all conditions surveyed, consistent with the removal of the highly acidic carboxyl terminus. Vapor diffusion experiments using subtilisin-cleaved tubulin under conditions where native tubulin forms needles or plates resulted in similar aggregates. PMID- 1898104 TI - The influence of detergents on the availability of pertussis toxin substrates. AB - Pertussis toxin-dependent ADP-ribosylation of rat heart and human mononuclear leukocyte membranes was found to be markedly enhanced in the presence of detergents. The order of potency for this effect of detergents was Triton X-100 approximately Lubrol PX greater than digitonin much greater than cholate greater than 3-[(3-cholamidopropyl)dimethylammonia]propanesulfonic acid. Exposure of membranes to increasing concentrations of detergents increased the proportion of pertussis toxin substrate demonstrable in the supernatant fraction whereas the substrate remaining in the pellet fraction demonstrated a complicated relationship with the concentration of detergent. In complementary experiments, it was found that immunochemical detection of G proteins in the pellet fraction from suspensions previously incubated with a maximal concentration of detergent revealed a reduced presence of G proteins with a concomitant increase in the concentration of G proteins in the supernatant fraction; this situation was not observed at submaximal concentrations of detergent during the preincubation of myocardial membranes. The results suggest that the detergent-mediated enhancement of pertussis toxin's action to ADP-ribosylate susceptible G proteins is a complicated process that includes concentration-dependent creation of conditions favorable to the actions of the toxin as well as solubilization of the substrates for the toxin. PMID- 1898106 TI - The toxicity of chlorothalonil to aquatic fauna and the impact of its operational use on a pond ecosystem. AB - Chlorothalonil is a fungicide whose heavy use in eastern Canada gives it the potential for significant aquatic contamination. Laboratory bioassays and field treatments of a pond system were undertaken to determine the toxic effects of chlorothalonil on aquatic fauna. The 96-h LC50 of technical chlorothalonil for rainbow trout (Oncorhynchus mykiss) was 76 micrograms/L and was not significantly different (p less than 0.05) from that of the formulated product (Bravo 500). The 96-h LC50 of Bravo 500 for blue mussels (Mytilus edulis) and clams (Mya arenaria) was 5.9 mg/L and 35.0 mg/L respectively, while its 48-h LC50 to Daphnia magna was between 130 micrograms/L and 200 micrograms/L. Chlorothalonil exposure of Daphnia to concentrations as low as 32 micrograms/L significantly (p less than 0.05) increased the time to production of first young, but there were no delayed effects on number of young produced or growth at concentrations of 180 micrograms/L or less. Chlorothalonil was initially accumulated by blue mussels to concentrations approximately ten times greater than exposure concentrations; however, tissue concentrations returned to the same level as exposure concentrations within 96 h. Spraying of ponds resulted in mortality of caged water boatmen (Sigara alternata) and threespine stickleback (Gasterosteus aculeatus) which could be related to chlorothalonil exposure, however, caddisfly larvae (Limnephilus sp.), freshwater clams (Psidium sp.), water beetles (Haliplus sp.), scud (Gamarus spp.) and midge larvae (Chironomidae) did not suffer substantial chlorothalonil-induced mortality. Changes in endemic benthic invertebrate abundance after sprays were not remarkable or related to treatment. Faunal impacts in the pond were generally of a smaller magnitude than were predicted by bioassay results.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1898107 TI - Starch as a renewable finish to improve the pesticide-protective properties of conventional workclothes. AB - Because many pesticide handlers persist in wearing and reusing conventional workclothes, a renewable functional finish that enhances the pesticide-protective qualities of fabrics would be useful. This study investigated the ability of starch to act as a pesticide trap, preventing transfer and increasing removal by laundering, and the effect of carboxymethyl cellulose on release of pesticide in laundry. The retention and distribution of methyl parathion (MeP) on 65% polyester/35% cotton fabric was studied with four finishes: starch and carboxymethyl cellulose (CMC) as nondurable finishes; durable press resin (DP) and durable press/carboxymethyl cellulose (DP/CMC) as durable finishes. Starching with an add-on of 8% (w/w) effectively reduced the area of contamination and enhanced the removal of methyl parathion from polyester/cotton fabrics. Residual pesticide values for CMC, DP, and DP/CMC finishes were similar to that of the unfinished fabric. While distribution profiles of methyl parathion throughout the yarn and fiber structures were similar for all the finishes, lower concentrations of pesticide were observed on the cotton fibers from the starched fabric. Starch reduced the pesticide transferring by rubbing from both 100% cotton and 65% polyester/cotton fabrics. These studies support the intriguing theory that starch can act as a pesticide trap on the fabric surface to decrease pesticide transfer and to enhance pesticide removal. Extensive penetration studies, field studies, and additional investigation of fiber, yarn, and fabric parameters are needed to further quantify the effects of starch. PMID- 1898108 TI - Effects of cadmium on metal composition and adenylate energy charge in the sea star Asterias rubens L. AB - Sea stars, Asterias rubens, were exposed to 200 micrograms Cd/L or fed with mussels which contained about 70 micrograms Cd/g dry wt. After 5 weeks, cadmium in the pyloric caeca of directly and indirectly exposed sea stars had reached levels of 12 and 9 micrograms Cd/g dry wt, respectively. For both types of exposure, a reduction of 30% of the zinc levels in the pyloric caeca was found, which was correlated with a comparable displacement of zinc from the metallothionein-like proteins. Copper levels were increased in the pyloric caeca of directly exposed sea stars. In gonads, stomachs, and body wall of directly exposed sea stars, cadmium concentrations were 4 to 9 times higher than those in animals fed with Cd-contaminated mussels. Cadmium exposure also affected metal composition in these tissues. The ovaries contained relatively large amounts of zinc. Gel filtration chromatography revealed that this zinc and the accumulated cadmium were distributed over a large range of high-molecular-weight proteins. Both direct and indirect cadmium exposure resulted in a small, but significant decrease of the adenylate energy charge (AEC) in the pyloric caeca. In the gonads, no effect of the cadmium exposure could be demonstrated on the AEC, but in the ovaries a reduction of the adenylate pool was found. In semi-field experiments, stars were exposed to 25 micrograms Cd/L or fed with mussels collected from the heavily polluted Dutch Western Scheldt. After 6 months of direct or indirect exposure, cadmium in the pyloric caeca had reached comparable levels of 8 and 7 micrograms/g dry wt, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1898109 TI - A major factor contributing to the high degree of unexplained variability of some elements concentrations in biological tissue: 27 elements in 5 organs of the mussel Mytilus as a model. AB - It has long been known that a high degree of "unexplained" residual variability can occur in the concentrations of some elements in some biological tissues. Until now, no reasons have been found for the presence of such high levels of variability. The present study describes a factor which can adequately explain this phenomenon. It was found that elements which are stored primarily in an insoluble form showed much higher degrees of variability than those stored in a soluble form. Elements found primarily in an insoluble form are often isolated from cellular metabolism including any regulatory processes and may build up to high levels in some individuals. The groups of elements showing the highest levels of residual variability were the heavy metals, lanthanides and actinides. These groups tended to be stored primarily in an insoluble form as determined by subcellular fractionation. The groups of elements showing the lowest levels of residual variability were the alkali metals and non-metals which were found to occur primarily in a soluble form in mussel tissue. The elements of the kidney generally had higher levels of residual variability than those of any other organ probably because of the kidney's ability to store high concentrations of elements in insoluble granules. A study of the behavior of aluminum in the digestive gland suggests that elements associated with insoluble granules of sediment passing through the gut could contribute to the residual variability of these elements. The highest levels of residual variability were observed for zinc, silver and lead in the kidney while the lowest for rubidium in the gills.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1898110 TI - Toxicity of mercury, copper, nickel, lead, and cobalt to embryos and larvae of zebrafish, Brachydanio rerio. AB - The toxicity of mercury (HgCl2), copper (CuCl2: 5 H20), nickel (NiSO4: 6 H2O), lead (Pb(CH3COO)2: 3 H2O) and cobalt (CoCl2: 6 H2O) was studied under standardized conditions in embryos and larvae of the zebrafish, Brachydanio rerio. Exposures were started at the blastula stage (2-4 h after spawning) and the effects on hatching and survival were monitored daily for 16 days. Copper and nickel were more specific inhibitors of hatching than cobalt, lead, and mercury. Nominal "no effect" concentrations determined from the dose-response relationships (ZEPs, Zero Equivalent Points) for effect on hatching time were 0.05 microgram Cu/L, 10 micrograms Hg/L, 20 micrograms Pb/L, 40 micrograms Ni/L and 3,840 micrograms Co/L, and those for effect on survival time were 0.25 microgram Cu/L, 1.2 micrograms Hg/L, 30 micrograms Pb/L, 80 micrograms Ni/L, and 60 micrograms Co/L. The "no effect" concentrations for Ni, Hg and Pb are consistent with previously reported MATC values for sensitive species of fish. The "no effect" concentrations for copper are 1-2 orders of magnitude lower than previously reported values. The major reason for the latter discrepancy was considered to be the absence of organics that can complex copper ions in the reconstituted water that we used, which had a hardness of 100 mg/L (as CaCO3) and a pH of 7.5-7.7. Unexposed controls were started with embryos from different parental zebrafishes and the parental-caused variability in early embryo mortality, median hatching time and median survival time were estimated. PMID- 1898112 TI - Organochlorine levels in North Atlantic right whale (Eubalaena glacialis) blubber. AB - Polychlorinated biphenyls (PCBs), total DDT (DDT + DDE + DDD), dieldrin, heptachlor epoxide, chlordanes, and hexachlorobenzene (HCB) were found in blubber biopsies from endangered North Atlantic right whales (Eubalaena glacialis) in the Bay of Fundy and on Browns-Baccaro Banks. Analyses included four sex and age class composite samples from 1988, and 21 individual samples from 1989. Generally, PCBs demonstrated the highest wet weight residue levels (up to 1.9 micrograms/g), followed by total DDT (DDT + DDE + DDD) (trace to 0.47 micrograms/g). Relatively low residue levels in adult females suggest that transmammary organochlorine (OC) residue transfer occurs during lactation. The actual blubber residue loads may have been underestimated, because the samples were taken when the whales were depositing fat reserves and the samples may not have been representative of the remainder of the blubber. PMID- 1898111 TI - Polycyclic aromatic hydrocarbons in harp seals (Phoca groenlandica) from the Northwest Atlantic. AB - There is virtually no information available on concentrations of polycyclic aromatic hydrocarbons (PAH) in seals from any of the world's oceans. The largest harp seal population in the world is found in Canadian waters of the Northwest Atlantic. Samples of muscle tissue obtained from twenty eight harp seals ranging in age from foetuses to animals 22 years old were analyzed for total PAH and lipid content. Concentrations were determined in terms of crude oil and chrysene equivalents in line with recommendations of the International Oceanographic Commission. Overall, relatively low concentrations were found, the highest values being less than 1 ppm (microgram/g) in terms of chrysene equivalents and 4 ppm (microgram/g) in terms of petroleum hydrocarbon equivalents. The lowest concentrations were observed in fetal tissue. There was no evidence of bioaccumulation with age, the concentrations in juvenile seals (1-5 years) being higher than concentrations in older animals (6-20 years). There was also no correlation between PAH concentration and fat content. There is a possibility that the animals having elevated levels of PAH are from the Gulf of St. Lawrence herd, indicating the importance of obtaining more information on PAH levels in marine mammals and other organisms from this and similar regionally contaminated seas. PMID- 1898113 TI - Differences between freshwater and seawater killifish (Oryzias latipes) in the accumulation and elimination of pentachlorophenol. AB - Freshwater and seawater acclimated (FWA and SWA) killifish (Oryzias latipes) were exposed to pentachlorophenol (PCP) for 3-10 days. Uptake and clearance rates of FWA and SWA killifish were determined. The estimated bioaccumulation factors (BCF) of PCP for FWA and SWA killifish were 1680 and 370, respectively. The smaller uptake rate and faster clearance rate resulted in the lower BCF for SWA killifish. Fresh- and seawater killifish excreted the PCP metabolites, the glucuronide and sulfate conjugates of PCP; the major metabolite of freshwater killifish was PCP sulfate; for seawater acclimated fish, it was PCP glucuronide. The greater excretion of PCP glucuronide by seawater killifish may be responsible for the rapid elimination of PCP. PCP accumulation in killifish decreased with higher pH levels in both freshwater and seawater environments, but these differences were less than the effect of salinity. The results indicate that salinity can affect the accumulation and elimination of environmental pollutants in killifish. PMID- 1898114 TI - Contaminated sediments from tributaries of the Great Lakes: chemical characterization and carcinogenic effects in medaka (Oryzias latipes). AB - Sediments from four inshore industrial sites and a reference site in the Great Lakes were extracted with organic solvents to produce a crude extract, which was separated on alumina into two fractions: predominantly polycyclic aromatic hydrocarbons; and predominantly nitrogen-containing polycyclic aromatic compounds. Crude extracts were redissolved in acetone and analyzed by gas chromatography and gas chromatography-mass spectrometry. The acetone-redissolved crude extracts from the four industrialized sites contained 5.6-313.3 micrograms total polycyclic aromatic compounds/g sediment and 3.0-36.4 micrograms other compounds/g sediment. In addition to the typical EPA priority pollutants, a substantial amount (228.7 micrograms/g sediment) of alkyl-polycyclic-aromatic compounds was detected in sediments from one of the industrialized sites. Extracts from the reference site contained 1.55 micrograms total polycyclic aromatic compounds/g sediment. Medaka (Oryzias latipes) were exposed to multiple pulse doses of acetone-redissolved extracts and fractions. Medaka were also exposed to a known carcinogen, methylazoxymethanol acetate, to verify that chemicals produced tumors in the test fish. Acetone-redissolved extracts and fractions from contaminated sediments were toxic to medaka. Fin erosion and non neoplastic liver abnormalities were more prevalent in medaka after exposure to acetone-redissolved extracts and fractions from contaminated sediments. Neoplasms previously associated with chemical exposure in wild fishes were induced in medaka exposed to acetone-redissolved extracts and fractions from two of the contaminated sites, but not from the reference site or controls. These findings further support the hypothesis that chemical contaminants in sediments are involved in epizootics of neoplasms in wild fishes at contaminated sites. PMID- 1898115 TI - The response of the three brood Ceriodaphnia test to fifteen formulations and pure compounds in common use. AB - The three brood Ceriodaphnia dubia test was carried out on fifteen formulations and pure compounds presently in general use in a variety of treatment processes or as reference toxicants. The most toxic substances (LC50 (based on survival/EC50 (based on total progeny) less than 10 mg/L) were metallic Cu, tertiary dodecyl mercaptan, an antioxidant TIA-RCO T-424, Cu(NO3)2.3H2O, K2Cr2O7, NALCO 7139--a flocculent, DOWFAX 2EP--a surfactant, TB-66--an algicide and ammonia. Exposure to these compounds elicited the same response from C. dubia for the two endpoints examined--survival and reproductive success. Two antimicrobials, PROXEL GXL and DOWICIL 75, and the surfactant sodium lauryl sulfate, were slightly toxic (LC50/EC50 less than 100 mg/L) for both endpoints studied. Two coagulants, NALCO 7109 and NALCO 8120 and a flocculent PERCOL 757 were practically nontoxic (LC50 greater than 100 mg/L) to slightly toxic (LC50 less than 100 mg/L) when the survival endpoint was examined, but were moderately toxic (EC50 less than 10 mg/L) to slightly toxic (EC50 less than 100 mg/L) when the endpoint of reproductive success was examined. These formulations and pure compounds had generally a declining effect on mean brood size, though there were exceptions to this observation as the broods progressed in number. PMID- 1898116 TI - Zymosan-induced chemiluminescence of alveolar macrophages: depression by inorganic dust constituents. AB - A method has been developed which allows the incubation of alveolar macrophages as weakly affixed monolayers in siliconized glass dishes. Without vigorous mechanical agitation and without using proteolytic enzymes, these cells were subsequently transferred to cuvettes where the zymosan-stimulated chemiluminescence of the suspended cells was measured. In vitro incubations of activated rabbit alveolar macrophage monolayers with airborne dusts from four West German sites (1 to 200 micrograms/10(6) cells), fly ash fractions of a special waste incinerator at Hamburg (50 to 1,000 micrograms/10(6) cells), and quartz dust DQ 12 (5 to 200 micrograms/10(6) cells) resulted in a dose- dependent depression of the zymosan-stimulated chemiluminescence. The depression of chemiluminescence was correlated with particle numbers, estimated dust surface, and antimony and lead masses of the dusts to which the cells were exposed. Cytotoxicity was better correlated with these parameters than with dust mass. PMID- 1898117 TI - Enhancement of mutagenicity of 1-nitropyrene by water as a diluent. AB - The mutagenicity of 1-nitropyrene was strongly enhanced in the Salmonella mutagenicity test with the preincubation modification when it was dissolved in dimethylsulfoxide and diluted with water. The enhancement of mutagenicity was not found in the plate incorporation method and seemed to be common to chemicals which have low solubilities in water. The indications were that the effectiveness of preincubation modification was due to the increased absorption of test chemicals by the Salmonella cells, and that the absorption depends primarily on the solubility of test chemicals in the assay mixture. PMID- 1898118 TI - Indoor air mercury concentrations following application of interior latex paint. AB - Mercury vapors are released from paint containing mercury compounds used to prolong the shelf-life of interior latex paint. To determine whether homes recently painted with paint containing mercury had elevated indoor-air mercury concentrations, we studied 37 Ohio homes. Twenty-one homes painted with mercury containing paint a median of 86 days earlier were compared with 16 homes not recently painted with mercury-containing paint. Paint samples from the exposed homes contained a median of 210 mg Hg/L (range 120-610 mg/L). The median air mercury concentration was higher in the exposed homes (0.3 microgram/m3; range nondetectable--1.5 microgram/m3) than in the unexposed homes (nondetectable; range nondetectable--0.3 microgram/m3, P less than 0.0001). Among the exposed homes there were seven in which paint containing less than 200 mg/L had been applied. In these homes, the median air mercury concentration was 0.2 microgram/m3 (range nondetectable--1 microgram/m3). Six (33%) exposed homes had air mercury concentrations greater than 0.5 microgram/m3, the acceptable indoor concentration recommended by the Agency for Toxic Substances and Disease Registry. Elemental mercury was the form of mercury released into the air. These data demonstrate that potentially hazardous mercury exposure may occur in homes recently painted with paint that contains mercury concentrations less than 200 mg/L. PMID- 1898119 TI - Lead exposure from conventional and cottage lead smelting in Jamaica. AB - A survey was conducted to determine the distribution and determinants of environmental and blood lead levels near a conventional and several cottage lead smelters and to assess the relationship between environmental and blood lead levels in a tropical, developing-country setting. Fifty-eight households were studied in the Red Pond community, the site of the established smelter and several backyard smelters, and 21 households were studied in the adjacent, upwind Ebony Vale community in Saint Catherine Parish, Jamaica. Households were investigated, using questionnaires, soil and housedust lead measurements, and blood lead (PbB) measurements from 372 residents. Soil lead levels in Red Pond exceeded 500 parts per million (ppm) at 24% of households (maximum--18,600 ppm), compared to 0% in Ebony Vale (maximum 150 ppm). Geometric mean PbB in Red Pond, where 44% of children less than 6 years of age had PbB levels greater than or equal to 25 micrograms per deciliter (micrograms/dL), was more than twice that Ebony Vale in all age groups (p less than 0.0005). Within Red Pond, proximity to backyard smelters and to the conventional smelter were independent predictors of soil lead (p less than 0.05). Soil lead was the strongest predictor of PbB among Red Pond subjects under 12 years of age. The blood lead--soil lead relationship in children differed from that reported in developed countries; blood lead levels were higher than expected for the household-specific soil lead levels that were observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1898121 TI - Effect of sublethal lead exposure on gastric motility of red-tailed hawks. AB - In order to determine the effects of low level lead exposure on gastric motility in raptors, strain gage transducers were surgically implanted on the serosal surface of the muscular stomach of three red-tailed hawks. The frequency and amplitude of gastric contractions during ingestion and early digestion were monitored for 1 week under control conditions and for 3 weeks while the birds were fed 0.82 or 1.64 mg lead (as lead acetate) per kg body weight each day. Exposure to these doses did not appreciably affect either the frequency or amplitude of gastric contractions in these birds. This low level lead exposure also had no consistent effect on the regular egestion of pellets of undigested material by hawks. Daily exposure to doses up to 6.55 mg lead/kg body weight did not affect the frequency or timing of pellet egestion, and exposure to 1.64 mg lead/kg did not affect the gastric contractions associated with pellet egestion. Although gastrointestinal dysfunction is often associated with clinical cases of acute lead toxicity, chronic exposure to these low levels of lead acetate did not significantly alter gastric motility in red-tailed hawks. PMID- 1898120 TI - Effects of chronic exposure to sublethal concentrations of lead acetate on heme synthesis and immune function in red-tailed hawks. AB - Red-tailed hawks were exposed to sublethal levels of lead acetate for periods of 3 or 11 weeks. Alterations in the heme biosynthetic pathway were demonstrated after the first week of exposure to 0.82 mg lead per kilogram body weight per day. Activity of erythrocyte porphobilinogen synthase (aminolevulinic acid dehydratase) was depressed significantly and did not return to normal levels until 5 weeks after the termination of lead treatments. A rapid and relatively brief increase in erythrocyte free protoporphyrin and a slower but more prolonged increase in its zinc complex were also demonstrated with exposure to this dose of lead for 3 weeks. Less substantial decreases in hematocrit and hemoglobin levels occurred but only in the longer experiment with exposure to higher lead levels. Short term, low level lead exposure did not effect immune function significantly in the hawks, as measured by antibody titers to foreign red blood cells or by the mitogenic stimulation of T-lymphocytes. Increased lead exposure produced a significant decrease in the mitogenic response but had no effect on antibody titers. PMID- 1898122 TI - Secondary poisoning hazard of fenthion to American kestrels. AB - The possibility that fenthion, an organophosphorus pesticide, could represent a secondary poisoning hazard to birds of prey was tested, using American kestrels (Falco sparverius) and house sparrows (Passer domesticus) as representative models of a naturally occurring predator-prey interaction. Fourteen kestrels were presented with live sparrows exposed previously to perches containing Rid-A-Bird 1100 solution (11% fenthion active ingredient). Eleven kestrels died within twenty-four h after consuming one fenthion-exposed sparrow. Two kestrels died after consumption of a second fenthion-exposed sparrow on day 2, and a final kestrel died after partially consuming a third fenthion-exposed sparrow on day 3. Brain cholinesterase (ChE) activity in kestrels was depressed to levels diagnostic of poisoning by a ChE-inhibiting compound. The majority of fenthion contamination of sparrows was external, with the highest amounts measured on the feet. The detection of fenthion residues in kestrel gastro-intestinal tracts confirmed secondary fenthion poisoning. PMID- 1898123 TI - Psychosomatic aspects of galactorrhea. AB - We interviewed 33 women with non-puerperal galactorrhea, 5 (15%) of whom had HPRL levels greater than 18 ng/ml and 24 controls, namely women with benign breast lesions. We used a semi-structured interview covering the duration of symptoms, preceding life events and the effect on the relationship of the couple. We also used the Beck depression inventory, the Strauss and Appelt body image questionnaire and an 8 item Visual Analogue Scale (VAS). Galactorrheic women were more depressive (P less than 0.1), had more prior life events (P less than 0.001), longer duration of symptoms (P less than 0.01), and less fear of their disease (P less than 0.05) than did controls. Both groups had similar results with the body image questionnaire. Within the study group, results were independent of prolactin (HPRL) levels or amenorrhea. PMID- 1898124 TI - Orthostatic hypotension and birthweight. AB - This study was designed to test two hypotheses. First, that the changes in arterial blood pressure, induced by a transition from a lying to a standing position, are different in early and late pregnancy. Second, that birthweight is related to the change in mean arterial blood pressure in late pregnancy such that those patients whose pressure fell on standing should have the lightest babies. Fifty-three patients were studied between the 12th to 18th week, and 41 women were between the 34th to 40th week of an accurately dated, clinically normal, singleton pregnancy. Twelve nulliparous females served as controls. Blood pressure and heart rate were measured at rest, then in the standing position and finally at rest again with a Dinamap blood pressure measuring device. The variability in the pressor response to standing was approximately three times and in heart rate response two times greater in early pregnancy and in late pregnancy, when compared to the nonpregnant controls. It should be further noted that only in late pregnancy did the heart rate fall in 10 out of 41 women on standing. A linear relationship was observed in late pregnancy between the change in mean arterial blood pressure and birthweight (r = 0.57, P less than 0.001). This linear relationship was improved to r = 0.86, when only those women (16/41), who either had a rise or fall in systolic blood pressure of more than 5 mm Hg were included. These data indicate that pregnancy increases the variability in the pressor response to standing. Moreover, birthweight was directly related to the magnitude and direction of the pressor response in late pregnancy. Finally, this relationship suggests an additional cause for unexplained cases of intrauterine growth retardation. PMID- 1898125 TI - Perforation of a pyometra mimicking a perforated peptic ulcer. AB - We report on a patient with a pyometra which leaked into the peritoneal cavity and was mistaken for a perforated peptic ulcer. There was no associated stenosis of the cervical canal. PMID- 1898126 TI - Thrombotic occlusion of an umbilical vein varix causing fetal death. AB - Acute thrombosis of an umbilical vein varix in combination with a single umbilical artery is a rare cause of fetal death. We now report such a case. PMID- 1898127 TI - Arterial switch for palliation of subaortic stenosis in single ventricle and transposition: no mean feat! PMID- 1898128 TI - Assessing the effect of cardiopulmonary bypass on the brain. PMID- 1898129 TI - Operations for subaortic stenosis in univentricular hearts. AB - Optimal prevention and treatment of subaortic stenosis (SAS) in the univentricular heart with subaortic outlet chamber and high pulmonary blood flow remains controversial, especially when complicated by aortic arch obstruction. Herein we analyze our surgical results. Group 1 consisted of 11 infants (mean age, 10 days) with univentricular heart and SAS. Ten required repair of interrupted aortic arch (n = 7) or coarctation with hypoplastic arch (n = 7). Four patients had relief of SAS by either Damus-Kaye-Stansel connection (n = 2) or aortopulmonary window (n = 2), with three operative deaths and one late death. Six had one-stage arterial switch and atrial septectomy with arch repair (5/6) with one operative death and one late death. Two survivors have progressed to bidirectional cavopulmonary shunt, a third has had a Fontan operation, and a fourth awaits Fontan. In group 2, 11 children required operation for acquired SAS after pulmonary artery banding. Nine have progressed to Fontan operation with either staged (n = 3) or concurrent (n = 6) relief of SAS by Damus-Kaye-Stansel connection or subaortic resection. Fontan mortality was 11% (70% confidence limits, 2% to 32%). Group 3 consisted of 3 patients without pulmonary artery banding who had SAS diagnosed at Fontan evaluation. All 3 survived Fontan operation and relief of SAS by Damus-Kaye-Stansel connection or subaortic resection. Group 4 consisted of 1 patient with previous pulmonary artery banding (no SAS) who underwent Fontan operation but required Damus-Kaye-Stansel connection 30 months later for SAS.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1898130 TI - Bilateral sequential lung transplantation: the procedure of choice for double lung replacement. AB - We recently described a technique for bilateral sequential lung transplantation that replaces the en bloc double-lung operation, a procedure that was accompanied by frequent problems with airway healing. Twenty-seven patients have undergone 28 bilateral sequential lung transplantations over the past 14 months. Eighteen patients had transplantation because of end-stage emphysema; 6, cystic fibrosis; and 1 each, obliterative bronchiolitis, usual interstitial pneumonitis with pulmonary fibrosis, and bronchiectasis. Cardiopulmonary bypass was used electively in the first 5 patients until it was recognized that the procedure could be done safely without it, and in only 3 additional recipients has it been employed. Mean ischemic time for the first lung was 276 +/- 43 minutes and for the second lung, 410 +/- 64 minutes. There have been five deaths, three in the postoperative period (11% operative mortality) and two late. The other patients are alive and well and do not require oxygen 2 to 15 months after transplantation. Mean forced expiratory volume in 1 second rose from 16% +/- 8% of predicted to 84% +/- 17% at 12 weeks. Six-minute walk values increased from a mean of 251 +/- 91 m to 666 +/- 42 m at 24 weeks. The excellent exposure afforded to both hemithoraces by the thoracosternotomy incision and the rare need of cardiopulmonary bypass have allowed us to offer the option of transplantation to patients who formerly would have been turned down because of previous pulmonary resection or pleurectomy. On four occasions, ventilator-dependent patients underwent successful transplantation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1898131 TI - Indications and limitations of aortic valve reconstruction. AB - To elucidate the value of conservative operation for aortic regurgitation, all consecutive patients operated on between July 1988 and July 1990 were reviewed. Of 251 patients with aortic regurgitation, 107 (42.6%) had nonprosthetic operation. The mean age was 23 years, and 90 patients (84.1%) were rheumatic. Two techniques were used: repair (annular and leaflet plasties, 69 cases) and cusp extension with glutaraldehyde-treated pericardium (25 bovine, 13 autologous). There were two hospital deaths (1.8%), both in the repair group, and no late deaths or embolic events. Only 5 patients (4.7%) were anticoagulated. In the repair group there were 12 reoperations, four (5.9%) due to aortic and eight to mitral dysfunction. In the cusp extension group there were two reoperations due to mitral dysfunction. Echocardiographic follow-up showed better results with cusp extension. In conclusion, conservative operation for aortic regurgitation is possible in a high percentage of young rheumatic patients and does not require anticoagulation. Cusp extension is more reliable than repair in terms of early results, although its long-term durability is not yet known. PMID- 1898132 TI - Warm heart surgery and results of operation for recent myocardial infarction. AB - Revascularization procedures after recent myocardial infarction are associated with higher mortality and morbidity compared with elective coronary artery bypass grafting. Traditional methods of myocardial protection impose a further ischemic insult on already compromised myocardium. Continuous cold blood cardioplegia may eliminate ischemia but may still leave the heart anaerobic. Theoretically, warm aerobic arrest addresses both of these issues and may become an attractive alternative to standard hypothermic ischemic arrest in this setting. In 115 nonrandomized patients undergoing coronary artery bypass grafting within 6 hours to 7 days of an acute myocardial infarction, myocardial protection was provided with continuous cold (4 degrees C) or continuous warm (37 degrees C) blood cardioplegia. Fifty-one patients (after 1988) protected with warm blood cardioplegia were compared with a historical cohort of 64 patients (before 1988) protected with cold blood cardioplegia. Results indicate that the warm cardioplegia group had no mortality versus 10.9% for the cold group (p less than 0.05), a myocardial infarction rate of 2.0% in the warm versus 9.3% in the cold group, and use of intraaortic balloon pump of 0% versus 12.5%, respectively (p less than 0.05). It is concluded that continuous warm aerobic arrest may minimize ischemia and anaerobic metabolism during the operative procedure, and may be of benefit to patients who have a limited tolerance to ischemic insult. PMID- 1898133 TI - Current treatment for Wolff-Parkinson-White syndrome: results and surgical implications. AB - From July 1986 to January 1991, 123 patients with Wolff-Parkinson-White syndrome underwent operation for ablation of aberrant conduction pathways. There were 85 male and 38 female patients ranging in age from 11 months to 68 years. Associated anomalies included Ebstein's anomaly, sudden death syndrome, coronary artery disease, cardiomyopathy, abdominal aortic aneurysm, neurofibromatosis, other arrhythmias, or other complex congenital heart disease. Forty-one patients had multiple accessory pathways. Operative results showed a 7% initial failure rate, which dropped to 3% after reoperation. One patient had undergone previous operation for Wolff-Parkinson-White syndrome at another institution. Procedures performed concomitantly included mitral or tricuspid valve repair or replacement (6), right ventricular conduit replacement, subaortic resection, Fontan repair, corrected transposition repair, coronary artery bypass, and placement of an automatic internal cardioverter defibrillator. There was no operative mortality. Late follow-up is 27 +/- 16 months, and complications included mitral regurgitation and myocardial infarction. By comparison, in the last 12 months 124 patients with the Wolff-Parkinson-White syndrome underwent catheter ablation using radiofrequency current. There were 9 patients with multiple pathways. One hundred twelve patients (90%) had all accessory atrioventricular connections ablated and have remained free of symptomatic tachycardia. There have been 12 failures (10%), of which 5 have had operation and 7 are being treated medically. Mean follow-up is 7 +/- 5 months, and complications included circumflex coronary artery occlusion, excessive bleeding, valve perforation, and cerebral vascular accident.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1898135 TI - Acute postinfarction septal rupture: long-term results. AB - From 1973 to 1989, 66 patients received early surgical repair for acute postinfarction ventricular septal rupture. Mean age was 64 +/- 7 years (range, 45 to 80 years). Ventricular septal rupture occurred soon after acute myocardial infarction (3.4 +/- 4 days), and the first medical treatment occurred 6.7 +/- 7 days after onset of acute myocardial infarction. Three patients had a previous myocardial infarction. The site of the rupture was anterior in 38 patients (57%) and posterior in 28 (43%). Forty-four patients (67%) were in shock at the time of admission. Intraaortic balloon pumping was used preoperatively in 28. Operation was performed at the time of maximal efficacy of medical treatment. The same technique was used in all cases. Associated procedures included coronary bypass grafting in 5 patients and valvar operation in 5. The patients have been carefully followed up for up to 16 years. Hospital mortality was 45% (30 patients) and was cardiac related or due to acute renal failure in 25 patients (83%). No correlation could be revealed between early death and age, sex, preoperative intraaortic balloon pumping, or year of operation. Location of the ventricular septal rupture (early mortality of 57% for posterior versus 37% for anterior ventricular septal rupture) and shock at the time of admission (52% versus 32%) showed a trend toward significance (0.08 less than or equal to p less than 0.10). Response to initial active therapy has a strong predictive value (mortality of 70% in unresponsive patients versus 14% in responders; p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1898134 TI - DNA ploidy patterns of tumors diagnosed as metachronous or recurrent lung cancers. AB - The relationship between the first tumor and the second tumor resected in 8 patients with non-small cell lung cancer was analyzed using deoxyribonucleic acid (DNA) flow cytometry. Of the 8 patients, 6 were clinically diagnosed as having metachronous lung cancers and 2, local recurrent tumors. The mean interval between operations in patients with metachronous lung cancers was 62 months (range, 15 to 128 months). Both tumors showed the same histology in 4 patients and a different histology in 2. In the 2 patients with local recurrent tumors, the interval between operations was 9 months and 39 months. In the analysis of DNA flow cytometry of the first and second tumors in the same patient, the tumors were defined as independent of each other when one tumor showed diploidy and the other, aneuploidy, or when each DNA index of abnormal clones between two aneuploid tumors was different. When both tumors showed diploidy or when at least one DNA index of abnormal clones between two aneuploid tumors was identical, the tumors were defined to be related to each other. According to these criteria, in 5 (83%) of the 6 patients clinically diagnosed as having metachronous lung cancers, the second tumor was classified as independent of the first tumor. On the other hand, in the 2 patients clinically diagnosed as having recurrent tumors, the second tumor was judged to be related to the first tumor. These data suggest that DNA flow cytometric analysis of tumors may be of value in the diagnosis of metachronous lung cancers. PMID- 1898136 TI - The healing sternum: a comparison of osseous healing with wire versus rigid fixation. AB - Although median sternotomy is used for most cardiac procedures, postoperative dehiscence remains a serious and persistent problem. This investigation was designed to assess new bone formation and sternal healing across the linear osteotomy of the sternum and to determine if rigid fixation would enhance bony healing and thus decrease unfavorable sequelae. To test this hypothesis, 14 skeletally mature baboons (Papio anubis) underwent standard median sternotomy; seven sternotomies were closed with interrupted 24-gauge cerclage wires, and seven, with thin Vitallium compression miniplates and transverse lag screws. The sterna from each group were harvested en bloc at 4 and 8 weeks, radiographed, processed, and serially sectioned and stained for histomorphometry to assess the quantity of new bone across the linear osteotomy. Clinical stability was superior with the plated and lag screw group at 4 weeks; however, by 8 weeks, no clinical difference between treatments was apparent. Histomorphometric analysis indicated that the linear osteotomy gap treated with plates and screws was less than the gap associated with the wire group. Rigid fixation of the sternum resulted in earlier union with primary osseous healing, suggesting greater inherent stability. these factors may decrease adverse sequelae for this procedure. PMID- 1898137 TI - Conventional blood conservation techniques in 500 consecutive coronary artery bypass operations. AB - With use of a nonpharmacological, simple, and inexpensive program for blood conservation, 500 consecutive patients underwent elective coronary artery bypass grafting without need of homologous red cell transfusions in 493 (98.6%). At least one internal mammary artery was grafted in all but 1 patient, with supplemental saphenous vein grafts. Intraoperatively, autologous heparinized blood was removed before bypass and retransfused at the conclusion of extracorporeal circulation. The volume remaining in the oxygenator and tubing set was returned without cell processing or hemofiltration. Using the hard-shell cardiotomy reservoir from the heart-lung machine, autotransfusion of the shed mediastinal blood was continued hourly up to 18 hours after operation. The mean postoperative mediastinal blood loss was 643 +/- 354 mL, whereas 624 +/- 296 mL was autotransfused. Thirteen patients (2.6%) needed reexploration for bleeding, of whom 7 (7/500, 1.4%) received homologous blood. No other patients required red cell transfusions. In addition, 9 patients were given a mean of 2.6 units of fresh frozen plasma because of suspected coagulopathy. No platelets were transfused, and no cryoprecipitate therapy was undertaken. Thus, in total, 484 patients (96.8%) were not exposed to any homologous blood products during the hospital stay. At discharge, the mean hemoglobin concentration was 121 +/- 14 g/L (12.1 +/- 1.4 g/dL) and the hematocrit, 0.36 +/- 0.04. Postoperative complications were few. There was one in-hospital death (0.2%). PMID- 1898138 TI - Treatment of cardiogenic shock with the Hemopump left ventricular assist device. AB - A multiinstitutional study is in progress to evaluate the Hemopump in the treatment of cardiogenic shock. Fifty-three patients with refractory cardiogenic shock were selected for Hemopump assistance. The hemodynamic definition of cardiogenic shock included (1) a cardiac index of less than 2.0 L.min-1.m-2, (2) pulmonary capillary wedge pressure of greater than 18 mm Hg, and (3) a systolic blood pressure of less than 90 mm Hg or a left ventricular work index of less than 1,500 g-m.m-2.min-1. The Hemopump was successfully inserted in 41 of 53 patients (77.3%). A significant improvement in the hemodynamic status was seen during Hemopump assistance. A minimal level of hemolysis was observed. No leg ischemia was observed. The 30-day overall survival of the Hemopump group was 31.7%. Criteria establishing indications for use and clinical utility are proposed. We conclude that the Hemopump provides significant hemodynamic support of the patient in cardiogenic shock allowing for recovery from ventricular stunning in marginal ventricles, and that in select patients the Hemopump may offer a major improvement in survival over conventional therapy. PMID- 1898139 TI - Sepsis after coronary bypass grafting: evidence for loss of the gut mucosal barrier. AB - Postoperative infections may originate from a patient's gastrointestinal tract. We studied infections after coronary artery revascularization. Three hundred twenty-nine patients underwent coronary artery revascularization from January 1987 to March 1990. Eight of the 329 (2.4%) died; none of the deaths were infection related. Fifty-five culture-proven infections were identified in 22 of 321 survivors (6.8%); 9 infections (16%) were gram-positive, 5 (9%) were fungal, and 41 (75%) were gram-negative. Site of infections were respiratory tract, 58%; urinary tract, 18%; blood, 13%; and mediastinum, 11%. Ninety-six percent of respiratory tract and all urinary tract infections were gram-negative or fungal. There was no significant difference between infected and noninfected groups in sex, age, smoking history, preoperative hematocrit or leukocyte count, serum albumin level, or time on extracorporeal bypass. The infected group required intubation and nasogastric suction for a significantly longer time than the noninfected group (p less than 0.001). Time to enteral alimentation was significantly longer in the infected group (p less than 0.02). We were unable to correlate the number of infections with the lengths of intubation, nasogastric suction, or time to enteral alimentation. This study supports the concept of postoperative infections arising from bacterial translocation across the patient's gastrointestinal tract. The most significant risk factor is the length of the gastrointestinal tract disuse. PMID- 1898140 TI - Early postoperative sternal approximation after ITA harvesting: computed tomographic evaluation. AB - Between November 1989 and February 1990, 66 randomized sternotomized patients underwent aortocoronary bypass and were subjected to a sternal scanner in the early postoperative period. Each examination included a manubrial and a sternal body print. At each level, we studied the occurrence of spacing or misalignment of the sternal layers. The 66 patients were subdivided into four groups according to the type of conduit harvested (single left internal thoracic artery or saphenous vein) and the type of material used for the sternal closure (steel wires or nylon yarns). In all cases, adequate early sternal approximation, which is represented by a good alignment as well as by an excellent contact of the sternal layers, was infrequently demonstrated. Moreover, the two abnormalities most often observed were manubrial spacing and sternal body misalignment. The sternal closure technique and internal thoracic artery harvesting had no significant effect on the sternal approximation. To minimize manubrial spacing and sternal body misalignment, we propose that the surgeon should apply three threads through the manubrium, withdraw the shoulder roll beforehand, elevate both of the patient's shoulders, and maintain the two xyphoid layers in the same plane and in fairly close contact during the tightening of the wires. PMID- 1898141 TI - High potassium contents in organ preservation solutions cause strong pulmonary vasocontraction. AB - Euro-Collins (ECS) and UCLA-formula organ preservation solutions induced strong vasocontraction in porcine pulmonary arteries when studied in organ baths at temperatures of 37 degrees C and 30 degrees C. At 20 degrees C ECS induced a 30% contraction, but at 6 degrees C no contraction (n = 5) or a weak contraction (n = 1) was elicited. Neither prostaglandin E1 nor nifedipine caused any significant reduction of the vasocontraction elicited by ECS and UCLA. Krebs solution, enriched with potassium in amounts corresponding to those in ECS (115 mmol/L) or UCLA (30 mmol/L), induced vasocontraction comparing well with those induced by ECS or UCLA, indicating that it is the high potassium content that causes the vasocontraction. In a second experiment lung segments were stored at 4 degrees C for 9 hours in ECS, UCLA, or Krebs solution. Pulmonary arterial segments were then studied in organ baths at 37 degrees C. The choice of preservation solution did not significantly affect the contractile properties of potassium, noradrenaline, or the thromboxane mimic U-46619. To conclude, high potassium contents in organ preservation solutions induce strong pulmonary vasocontraction in lung temperatures greater than 20 degrees C but not in temperatures less than 10 degrees C. These vasocontractions are not significantly reduced by prostaglandin E1 or nifedipine. We suggest that the initial preservation solution used to cool down the lungs should contain 4 mmol/L or no potassium. When the lung temperature is less than 10 degrees C, a second perfusion might be done, and then a high potassium content (if thought to be essential) will not cause vasocontraction. PMID- 1898143 TI - Bezold-Jarisch reflex in postoperative pediatric cardiac surgical patients. AB - The Bezold-Jarisch reflex is an inhibitory reflex that originates from the heart, is mediated by the vagus nerve, and is manifested by hypotension and bradycardia. We present 4 pediatric cardiac surgical patients, aged 1 day to 9 months, who exhibited cardiovascular collapse in their early postoperative course. In each patient, cardiovascular deterioration was marked by an insidious decrease in arterial blood pressure without an associated change in heart rate, central venous pressure, or airway pressure. Bradycardia followed the decrease in blood pressure. The Bezold-Jarisch reflex was suspected and atropine was administered, first as a bolus injection at 0.01 mg/kg, and later, as a continuous infusion at 0.01 mg.kg-1.h-1. Atropine prevented recurrent episodes of hypotension and bradycardia. We believe the Bezold-Jarisch reflex is more prevalent than previously suspected in postoperative pediatric cardiac surgical patients. PMID- 1898142 TI - Prophylaxis of atrial fibrillation with magnesium sulfate after coronary artery bypass grafting. AB - Ninety-nine consecutive consenting patients were prospectively entered into a randomized, double-blind, placebo-controlled trial to determine the efficacy of postoperative magnesium therapy on the incidence of cardiac arrhythmias after elective coronary artery bypass grafting. No patient had documented or suspected arrhythmias preoperatively. Forty-nine patients received 178 mEq of magnesium given over the first 4 postoperative days, and 50 patients received only placebo. The clinical characteristics of both groups were similar. The preoperative mean serum magnesium concentration was similar in both study (1.90 mEq/L) and placebo (1.90 mEq/L) groups. The mean postoperative serum magnesium concentration in study patients was significantly elevated over postoperative days 1 through 4 when compared with preoperative levels (p less than 0.001). The postoperative mean serum magnesium concentration in control patients declined and remained significantly depressed through postoperative day 3 (p less than 0.001), but increased to preoperative levels by postoperative day 4. The mean serum magnesium concentration was significantly greater in the study patients as compared with the control patients over postoperative days 1 through 4 (p less than 0.001). Although there was no significant difference between groups with respect to episodes of ventricular arrhythmias, there was a significant decrease in the number of episodes of atrial fibrillation in the group receiving magnesium therapy (p less than 0.02). There were no recognized adverse effects of magnesium therapy. Prophylactic magnesium administration seems to lessen the incidence and severity of atrial fibrillation after coronary artery bypass grafting. PMID- 1898144 TI - Complement activation during bypass in acquired C1 esterase inhibitor deficiency. AB - Serial complement estimations during cardiopulmonary bypass are reported in a patient with acquired C1 esterase inhibitor deficiency. Although the extent of classic and alternative pathway activation appeared appropriate, exaggerated common pathway activation with massive increase in the C3d:C3 ratio occurred. A fatal hemostatic disorder, pulmonary edema, and circulatory collapse ensued despite prophylaxis and therapy. PMID- 1898145 TI - Bidirectional cavopulmonary anastomosis using vertical vein for right isomerism, pulmonary atresia, and TAPVR. AB - An 8-year-old girl who was diagnosed as having right atrial isomerism, pulmonary atresia, butterfly-shaped juxtaductal pulmonary arterial stenosis, total anomalous pulmonary venous return of the supracardiac type, regurgitant common atrioventricular valve, and univentricular heart of the right ventricular type underwent bilateral, bidirectional cavopulmonary anastomosis using a vertical vein and anastomosis between the common pulmonary venous trunk and atrium. The surgical procedure in this patient is described. PMID- 1898147 TI - Long-term function in University of Cape Town prostheses in the tricuspid position. AB - A 55-year-old woman undergoing triple-valve replacement was found at operation to have a well preserved and functioning University of Cape Town prosthesis that had been inserted 18 years earlier for tricuspid stenosis. Case reporting, valve reappraisal, and factual updating on another case, the world's first documented tricuspid valve replacement for Ebstein's anomaly, are presented. These two remarkable in vivo successes speak well for this historic collar stud valve. PMID- 1898146 TI - Large mediastinal mass secondary to an aortocoronary saphenous vein bypass graft aneurysm. AB - A case of a 62-year-old man with a large mediastinal mass who had undergone aortocoronary bypass grafting 17 years earlier is presented. Computed tomography showed a 13-cm extrinsic cystic mass believed to represent a pericardial cyst or teratoma. Intraoperatively, the patient was noted to have an aneurysm of his right coronary artery bypass graft. We were able to find 4 other cases seen in this manner. PMID- 1898149 TI - Pericardial mass mimicking constrictive pericarditis. AB - Persistent pericardial hematoma due to blunt chest trauma is extremely rare. We report a case of constricted myocardium resulting from a large, partially organized hematoma in the right cardiophrenic angle. The hematoma was assumed to be caused by an occupational accident 17 years before diagnosis. Constriction could only be controlled by complete removal of the fibrous posterior capsule of the hematoma, which covered the epicardium of the right heart. PMID- 1898148 TI - Schwannoma of the brachial plexus mimicking an apical lung tumor. AB - Primary tumors of the brachial plexus are unusual. We describe a patient with a large schwannoma of the lower trunk of the brachial plexus that had the radiologic appearance of an apical lung mass. Use of a posterior subscapular approach as well as intraoperative nerve action potential recording permitted resection with spared function. PMID- 1898150 TI - Perfusion without systemic heparinization for rewarming in accidental hypothermia. AB - We report on a patient with accidental deep hypothermia (23.3 degrees C) and cardiorespiratory arrest resulting from severe craniocerebral injury. Systemic anticoagulation was contraindicated, and the decision was reached to rewarm the patient with cardiopulmonary bypass without systemic heparinization using heparin coated perfusion equipment. The patient was successfully rewarmed, was weaned from cardiopulmonary bypass, and recovered. PMID- 1898151 TI - Peritoneopericardial diaphragmatic hernia discovered at coronary bypass operation. AB - A 68-year-old man was discovered to have a large peritoneopericardial hernia when operated on for coronary artery bypass. Such hernias are very unusual. The pathogenesis, clinical presentation, and management of this problem are discussed. PMID- 1898152 TI - Optimal visualization of coronary artery anastomoses by gas jet. AB - A technique is described for improved visualization during the creation of coronary artery anastomoses employing a catheter-directed constant stream of oxygen to remove blood from the operative field. This technique is especially helpful when continuous blood cardioplegia is employed for myocardial protection. PMID- 1898153 TI - Myocardium-sparing cannulation technique for left ventricular assist device support. AB - The left atrium and the left ventricular apex are the most commonly used sites of inflow cannulation for postcardiotomy left ventricular support. A new cannulation technique that requires only an ascending aortotomy is introduced. This procedure can be undertaken with equipment present in any cardiac operating room and may prove to cause fewer complications than conventional cannulation techniques. PMID- 1898154 TI - Resternotomy in patients with valved conduits adherent to the sternum. AB - Twenty-two patients with valved conduits adherent to the sternum underwent resternotomy. Mean age was 10 +/- 6 years, and mean conduit age was 4 +/- 4 years. Diagnoses were D-transposition (7), truncus arteriosus (7), univentricular heart (6), Taussig-Bing anomaly (1), and corrected transposition (1). The majority of patients (68%) had reoperation for outgrown or degenerated conduits. In 17 patients, the sternum was opened with a chisel. Two of these patients sustained conduit neointimal collapse from manipulation, and 3 had conduit tear requiring immediate cardiopulmonary bypass through the femoral vessels. In the last 5 patients, the sternum was opened above and below the conduit, and the inner table was chiseled and left attached to the conduit avoiding injury and undue conduit manipulation. Cardiopulmonary bypass and operation were carried out uneventfully. We believe that the recent technique described provides a safe alternative approach to valved conduits adherent to the sternum. PMID- 1898155 TI - Surgical cure of cardiac arrhythmia. 1969. AB - The first surgical procedure undertaken for the intended purpose of curing a patient with recurrent tachycardia was performed by Sealy in 1968, and the report of that operation was published in The Annals of Thoracic Surgery in 1969. The first attempted accessory bundle ablation was successful, marked the beginning of cardiac arrhythmia surgery, and has set the standard against which other methods of arrhythmia control must be measured. PMID- 1898156 TI - Cystic and bullous lung disease. AB - One of the most difficult problems facing clinicians is the evaluation and management of patients with dyspnea whose chest roentgenogram shows single or multiple large cystic spaces. This is made more difficult when underlying lung disease is present. The dilemma focuses on whether the obliteration or removal of the cystic areas will benefit or cause further deterioration of the patient's condition. The pathophysiology of the problem is not completely understood, but accumulated clinical experience has shown that surgical therapy can be beneficial but requires proper patient selection. PMID- 1898157 TI - Balloon angioplasty of aortic coarctation. PMID- 1898158 TI - Unusual complication of J wire used for central venous cannulation. PMID- 1898159 TI - Aortic vent efficiency. PMID- 1898160 TI - Role of thoracoplasty in the treatment of chronic empyema. PMID- 1898161 TI - Diuresis in hemodynamically compromised patients. PMID- 1898162 TI - Surgical correction of coarctation in early infancy: does surgical technique influence the result? AB - Between 1979 and 1988, a total of 53 infants less than 1 year of age underwent repair of coarctation. Thirty-seven patients (70%) were younger than 3 months. Median age was 0.9 month. Four different surgical techniques were used: resection with end-to-end anastomosis, patch enlargement, subclavian flap aortoplasty, and subclavian displacement aortoplasty (Meier-Mendonca technique). Hospital mortality was 7.5% and was limited to patients with additional complex intracardiac defects. Neither age nor surgical technique had an influence on the operative risk. Follow-up averaged 15 to 43 months for the four different groups. Restenosis developed in 9 (19%) of 47 patients regularly followed up, 5 (11%) of whom have had reoperation. Age at operation was not a predictor for restenosis, which occurred in 17.4% of patients less than 1 month and 20.8% of those greater than 1 month of age at operation. Patch enlargement and the subclavian displacement technique demonstrated the highest restenosis rates (42% and 43%, respectively). However, patients who underwent patch enlargement had less favorable pathological conditions. It is concluded that results of coarctation repair in early infancy do not depend as much on the operative method itself as on the specific pathological aspect, which largely determines the method of treatment. Some reservation must be made in regard to the subclavian displacement technique. PMID- 1898163 TI - Coarctation: do we need to resect ductal tissue? AB - A review of the literature as well as a retrospective review of 100 neonates undergoing operation for coarctation at Children's Hospital in Boston between 1972 and 1984 has not established clear superiority for either resection and end to-end anastomosis or subclavian flap aortoplasty with respect to risk of recurrent coarctation. However, there is histological evidence that the juxtaductal coarctation shelf is composed of smooth muscle of ductal origin, which subsequently fibroses. This abnormal tissue may be at risk for late aneurysm development, particularly if balloon dilatation angioplasty is required. The fact that this abnormal tissue is not removed by the subclavian flap procedure is one of the inherent disadvantages of that procedure. Other disadvantages include the need to sacrifice the left subclavian artery and the fact that, unlike resection and end-to-end anastomosis, the subclavian flap procedure does not lend itself to augmentation of the hypoplastic distal aortic arch. Furthermore, occasionally a secondary coarctation membrane is present within the distal aortic arch, and though it is readily detected during the resection procedure, it can be missed with the subclavian flap procedure. Based on these considerations rather than on a demonstrated superiority of either procedure, my colleagues and I currently prefer resection and end-to-end anastomosis over subclavian flap aortoplasty. PMID- 1898164 TI - Coarctation and hypoplasia of the aortic arch: will the arch grow? AB - Hypoplasia of the transverse aortic arch of various degrees of severity is commonly seen in infants who have coarctation of the aorta. It is more often present when the coarctation is associated with intracardiac lesions that diminish or limit forward flow in the ascending aorta and promote right to left flow through an arterial duct. The increased frequency of surgical treatment of infants with complex coarctation, which is in part related to the ability to stabilize their condition with prostaglandin E1, has posed the question of the potential for growth and development of the originally hypoplastic aortic arch after conventional repair of aortic coarctation. Review of our experience with transverse aortic arch hypoplasia, found in 33 (32%) of 102 infants undergoing coarctation repair by subclavian flap aortoplasty or classic resection and end-to end anastomosis, revealed excellent growth of the transverse arch after repair in all patients available for linear follow-up. The currently proposed extended arch repair should be reserved for the small group of infants with transverse aortic arch to ascending aorta diameter ratios (arch indices) of less than 0.25. PMID- 1898165 TI - Role of extended aortoplasty related to the definition of coarctation of the aorta. AB - One hundred thirty-nine patients underwent operation for coarctation of the aorta. Age ranged from 1 day to 21 years and weight, from 1.5 to 70.4 kg. Numerous methods of repair were used. The operative mortality was low (1.3%), and 17 patients (11.3%) died late. Recoarctation occurred in 13 patients (9.4%). We attempted to correlate mortality and recoarctation with the surgical procedure. A review of the literature revealed no classifications of coarctation that applied to the anatomical and pathological variations we found at the time of operation. Therefore, we devised a surgical classification to separate the various entities in the spectrum of coarctation: type I = primary coarctation; type II = coarctation with isthmus hypoplasia; and type III = coarctation with tubular hypoplasia involving the isthmus and segment between the left carotid and left subclavian arteries. Each of these types has subtypes: A = with ventricular septal defect and B = with other major cardiac defects. We believe that rather than labeling one procedure as "the procedure of choice," providing this classification will allow the surgeon to use a method of repair that is suited to the anatomical variation. PMID- 1898166 TI - Staged repair of interrupted aortic arch and ventricular septal defect in infancy. AB - Staged repair of interrupted aortic arch and ventricular septal defect was carried out in 20 infants from 1979 through 1990. Among the important associated cardiac defects were transposition of the great arteries, truncus arteriosus, and anomalous origin of the right pulmonary artery. The first stage, usually consisting of the placement of an 8- or 10-mm polytetrafluoroethylene graft, pulmonary artery banding, and ligation of the patent ductus arteriosus, resulted in 20 survivors (100%) There were two interim deaths (10%) before the second stage of ventricular septal defect closure and pulmonary artery band removal, which had 15 survivors (83%, 15/18). Because the major morbidity and mortality early in this experience could be traced to leaving the pulmonary artery band on too long, early removal (within 2 to 3 months) was begun. Since 1985, 8 (100%) of 8 infants have survived both stages and are now doing well. Because of the relatively large polytetrafluoroethylene graft, only 1 child (aged 9 years) has experienced substantial late aortic arch obstruction and undergone placement of an 18-mm Dacron graft without difficulty. Of interest is the finding that in only 1 (5%) of the 20 patients has major (greater than or equal to 40-mm Hg gradient) left ventricular outflow tract obstruction developed. In summary, the staged repair of interrupted aortic arch with ventricular septal defect has become very reliable despite the condition of the infant or major associated cardiac anomalies and can be recommended for infants at high risk for primary repair. More long-term information will be needed to determine which approach will be the best choice for the majority of infants. PMID- 1898167 TI - The myth of the aortic annulus: the anatomy of the subaortic outflow tract. AB - Surgical repair of the small aortic root is limited in part by the very structure of the outflow tract from the left ventricle. The root is not constructed on the basis of a ringlike annulus supporting the leaflets of the aortic valve. The only truly circular structure within the outflow tract is the junction of the aortic wall with the underlying ventricular structures, themselves partly muscular and partly fibrous. This circular ventriculoarterial junction is crossed by the semilunar attachments of the leaflets of the aortic valve, producing an interlinking arrangement between the expanded aortic sinuses and three triangles of fibrous tissue placed beneath the apexes of the commissures between the valve leaflets. The triangles form extensions of the left ventricle that are related, in part, to the pericardial cavity surrounding the heart. The arrangements of the attachment of the leaflets in malformed valves with two (or only one) effective leaflets are highly abnormal, although these valves are usually produced on the template of three aortic sinuses. The valve with two leaflets rarely gives problems during childhood. In valves producing "critical stenosis", there is usually only one effective leaflet, a condition due to incomplete liberation of two of the anticipated three commissures. Detailed study shows that, in these malformed hearts, the attachment of the leaflets is much more annular than in normal valves, with inadequate formation of the fibrous triangles. PMID- 1898168 TI - Growth of the hypoplastic ascending aorta after radical palliation. AB - Surgical treatment of hypoplasia of the ascending aorta is a difficult problem. An approach using proximal pulmonary artery to distal aorta bypass with distal pulmonary artery banding was employed in 19 patients with an ascending aorta less than 6 mm in diameter but a patent aortic outflow. There were 11 male and 8 female neonates and infants, and weight ranged from 2 to 4.5 kg (median weight, 3.5 kg). Four patients had transposition of the great arteries, 12 had subaortic stenosis, and 5 had interrupted aortic arch. There was one operative death. Cerebral cyanosis developed in 3 of the 4 patients with transposition of the great arteries and necessitated additional operations within the first year postoperatively. Therefore, palliation with a pulmonary artery to descending aorta conduit and banding was abandoned in such patients. All 14 surviving patients with normally related great arteries had successful palliation and growth of left heart structures. Subsequent procedures included a Fontan/Damus procedure in 1 patient, patch aortoplasty and pulmonary arterioplasty in 5 patients, arch reconstruction with aortic valvulotomy and pulmonary arterioplasty in 2, double arch reconstruction in 2, and simple patch aortoplasty with plans for subsequent pulmonary arterioplasty and ventricular septal defect closure in 1. Results demonstrate that in patients with a hypoplastic ascending aorta, this radical method of palliation can result in growth of right and left heart structures and thus provides the possibility of biventricular repair. PMID- 1898169 TI - Surgical management of diffuse subaortic stenosis: an integrated approach. AB - An integrated approach to the surgical management of diffuse subaortic stenosis has been designed to provide adequate relief of left ventricular outflow tract obstruction whatever the anatomical features encountered at operation. This approach was used in 22 patients with tunnel subaortic stenosis (19 patients) or diffuse hypertrophic obstructive cardiomyopathy (3 patients). The obstructive tissue was resected through an aortoseptal approach. In 18 patients, associated hypoplasia of the aortic orifice necessitated aortic valve replacement using the Konno procedure; in 4 patients with a normal-sized aortic orifice, the native aortic valve was preserved. There were two early deaths and one late death (all after a Konno operation). Long-term adequate relief of left ventricular outflow tract obstruction was achieved in all survivors. Operation for diffuse subaortic stenosis should be performed with two main goals: (1) to obtain complete relief of the left ventricular outflow tract obstruction by the appropriate procedure and (2) to preserve the native aortic valve whenever possible, particularly in young patients. PMID- 1898170 TI - Extended aortic valvuloplasty: a new approach for the management of congenital valvar aortic stenosis. AB - A new technique for the treatment of congenital valvar aortic stenosis is described. It consists of augmenting the aortic cusp by extending the commissurotomy incision into the aortic wall around the leaflet insertion, mobilizing the valve cusp attachment at the commissures, and freeing the aortic insertion of the rudimentary commissure. The results of standard valvotomy performed on 48 patients (group 1) were compared with those of the new extended valvuloplasty carried out on 16 patients (group 2). The two groups were comparable in age at operation (2.7 +/- 2.1 years for group 1 versus 2.1 +/- 1.7 years for group 2; p = not significant) and in preoperative pressure gradient (58 +/- 25 mm Hg for group 1 versus 61 +/- 36 mm Hg for group 2; p = not significant). There was no operative mortality in either group. Follow-up is available on all patients, with a mean of 4.3 +/- 2.6 years for group 1 versus 1.7 +/- 0.5 years for group 2 (p = 0.05). There was one late death in group 1. Postoperative gradient was 47 +/- 13 mm Hg in group 1 versus 19 +/- 13 mm Hg in group 2 (p = 0.05). Moderate or severe regurgitation was present in 18 patients (38%) in group 1 and 2 patients (13%) in group 2 (p = not significant). Reoperation was needed in 8 patients (17%) in group 1 versus 2 patients (13%) in group 2 (p = not significant). The described valvuloplasty procedure addresses the unique pathological features of valvar aortic stenosis and provides better relief of the obstruction than the presently available techniques. Longer follow up is needed to determine the late results of this approach. PMID- 1898171 TI - Extended aortic root replacement with cryopreserved allografts: do they hold up? AB - The extended aortic root replacement technique is used for the surgical repair of left ventricular outflow tract obstruction complicated by concurrent hypoplastic aortic annulus, multiple levels of obstruction, or aortic insufficiency. Extended aortic root replacement incorporates the concepts of aortic root replacement and aortoventriculoplasty to create a comparatively simple procedure. Unique features of the technique include the implantation of an allograft, which makes the need for anticoagulation obsolete, and use of the donor mitral leaflet to enlarge the outflow tract. Since 1985, 32 patients in Denver have undergone placement of a cryopreserved aortic valve allograft as part of extended aortic root replacement. There were four hospital deaths (13%), and 1 child underwent cardiac transplantation 30 hours after operation. In 6 months to 4.8 years of follow-up, a 14-year-old boy with familial hyperlipidemia required coronary artery bypass grafting, and 3 children experienced allograft calcification with progressive insufficiency, which prompted allograft replacement. The other 23 patients are clinically well. PMID- 1898172 TI - The Damus-Fontan procedure. AB - The Damus-Kaye-Stansel operation is a useful technique for the treatment of complex cyanotic congenital heart disease when there is obstruction between the systemic ventricle and the aorta. Modifications of the technique include transection of the aorta and the pulmonary artery, anastomosis of the contiguous aortic and pulmonary walls, and connection of the distal aorta to the perimeter of the new bivalved proximal great artery. In addition, the bidirectional cavopulmonary shunt technique can be used with or without the Fontan procedure. Six patients underwent a Damus-Fontan operation, and all survived. Two patients underwent the Damus-cavopulmonary shunt (hemi-Fontan) procedure, and 1 survived. The postoperative status of the 7 survivors is good to excellent. Follow-up ranges from 2 months to 7 1/2 years. PMID- 1898174 TI - Hypoplastic left heart syndrome. AB - The evolution of the present approach to the newborn with hypoplastic left heart is outlined. Preoperatively, maintenance of ductal patency with prostaglandin E1 and balancing of systemic and pulmonary blood flow are essential. Operative details of the first-stage palliation and the definitive second-stage procedure are described. The more recent adoption of an intermediate-stage hemi-Fontan procedure is also described. Since January 1989, 151 patients have been treated using this three-stage approach, with 109 early survivors. Seventy-eight have undergone the hemi-Fontan operation with nine deaths (5 of whom came to this stage early nonelectively because of shunt failure or ventricular dysfunction). Twenty-seven of the 78 patients undergoing hemi-Fontan operation have subsequently undergone definitive Fontan procedures with no deaths. PMID- 1898173 TI - The Damus-Stansel-Kaye procedure: anatomical determinants and modifications. AB - Seven of 119 patients undergoing anatomical correction for transposition of the great arteries and Taussig-Bing anomalies without pulmonary stenosis had the Damus-Stansel-Kaye procedure and the rest, the arterial switch. The age of the patients having the Damus-Stansel-Kaye procedure ranged from 0.5 year to 5 years (mean age, 2.2 +/- 1 years). Four patients had transposition, 2 had Taussig-Bing anomaly, and 1 had corrected transposition. Indications for the Damus-Stansel Kaye procedure were side-by-side great arteries associated with difficult coronary anatomy (5 patients), single coronary system (1 patient), and subaortic stenosis (1). A graft between the ascending and descending aorta for interrupted aortic arch made mobilization and posterior displacement of the ascending aorta for the arterial switch difficult. Subaortic stenosis (1 patient), subpulmonary ventricular septal defect (2 patients), and restrictive ventricular septal defect (4) precluded the Rastelli procedure. In 6 patients, the main pulmonary artery was transected at the band, a proximal main pulmonary artery to aorta anastomosis was complemented with a synthetic patch, and a right ventricle to distal main pulmonary artery valved conduit was inserted. Four patients had closure of the aortic outflow. Two patients had postoperative bleeding and 2, heart block. The only patient who did not have transection of the main pulmonary artery, an omission that led to an obstructed conduit at the distal anastomosis, died late. Two patients subsequently needed aortic outflow closure for critical aortic insufficiency. The Damus-Stansel-Kaye procedure has a definite role and can be safely performed in patients with transposition of the great arteries and Taussig Bing anomalies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1898175 TI - Intermediate procedures after first-stage Norwood operation facilitate subsequent repair. AB - Actuarial analysis of survival after first-stage palliative reconstructive operation for hypoplastic left heart syndrome has revealed a high out-of-hospital attrition rate over the first 18 months to 2 years postoperatively. Some of this mortality is related to development of anatomical problems such as restrictive atrial septal defect, neoaortic arch obstruction, and pulmonary artery distortion. The bidirectional Glenn shunt has proved to be an ideal adjunctive procedure for high-risk patients at the time of operation to correct such intermediate-term problems. The fenestrated Fontan procedure, which involves fenestration of the interatrial baffle placed as part of our current standard Fontan procedure, is applied for patients considered to be at moderate risk for a Fontan procedure. The decision regarding closure of the fenestration is made by hemodynamic study including temporary balloon occlusion of the fenestration. The fenestration is closed with the double-clamshell device, which is placed percutaneously in the catheterization laboratory and which is currently used for secundum atrial septal defect closure. Appropriate selection of patients for the bidirectional Glenn shunt or fenestrated Fontan procedure with or without fenestration closure has resulted in a dramatic decrease in mortality and morbidity for patients with all forms of single ventricle and for patients with hypoplastic left heart syndrome. PMID- 1898176 TI - Transplantation after first-stage reconstruction for hypoplastic left heart syndrome. AB - The surgical treatment of infants born with hypoplastic left heart syndrome has received considerable attention in recent years. Although this lesion was previously considered uniformly fatal, dramatic successes have been achieved with the use of staged reconstructive and replacement therapies. However, both surgical options have benefits and limitations, and neither has demonstrated clear superiority over the other. As survival for first-stage reconstruction by the Norwood procedure has improved, a greater number of patients are potential candidates for the Fontan operation, but not all will be suitable at an acceptable risk. These patients may be treated by cardiac transplantation. The results of a treatment protocol for 90 patients with classic hypoplastic left heart syndrome or its variants at The University of Michigan are reported, with particular attention given to those patients surviving initial palliation but judged to be unsuitable for a subsequent Fontan procedure. PMID- 1898177 TI - Pediatric heart and heart-lung transplantation. PMID- 1898178 TI - Heart transplantation in children: an international survey. AB - A survey of cardiac transplantation in children provided data from 381 transplantations in 362 patients from 32 centers in the United States and ten international centers. The number of transplantations continues to increase, in part because of transplantations in infants with hypoplastic left heart syndrome and patients with congenital defects. The immunosuppression regimens were more uniform than in the 1985 survey, and triple therapy was most common. Actuarial survival rates were 85% at 1 month, 72% at 1 year, 64% at 3 years, and 60% at 5 years. However, these improved rates are still not equal to the survival of the overall cardiac transplant population, in part because of lower survival rates in neonates. Ventricular dysfunction and rejection, rather than infection, were the leading causes of death. Rejection and infection were the most frequent complications. Also common were hypertension (39%) and seizures (25%), whereas coronary artery disease (8%) was unusual. Functional results were excellent in 85%, and only 7% were disabled. Questions concerning growth rates and many other aspects cannot yet be answered. However, it is apparent that cardiac transplantation in the pediatric population is a very worthwhile endeavor. PMID- 1898179 TI - Pediatric cardiac transplantation despite atrial and venous return anomalies. AB - Congenital anomalies of the atrium, pulmonary venous return, and systemic venous return are often regarded as anatomical contraindications to orthotopic cardiac transplantation. Among our pediatric transplant patients, 10 children aged 3 to 15 years, weighing 9 to 45 kg, and all previously operated on for a total of 18 interventions had 32 anomalies needing correction at the time of transplantation. Besides the 18 instances of great vessel abnormalities, 14 anomalies of the atrium and of the venous return were encountered either alone or in combination: single atrium or previous septectomy (4), hypoplastic left atrium (2), previous Mustard procedure (1), cor triatriatum (1), anomalous pulmonary venous return (3), and anomalous systemic venous return (3). The preparation of the donor heart was modified in four ways: right atrial paraseptal incision, left atrial flap technique, full-length mobilization of the pulmonary arteries, and aortic arch incision. Correction of the atrial and venous return anomalies was carried out at the time of orthotopic transplantation with the following techniques: atrial septation, atrial enlargement, superior systemic venous return reroofing, inferior systemic venous return reroofing, double venous rerouting (pulmonary and systemic), and septal realignment. One child died of pulmonary hypertension in the early postoperative period. After a follow-up ranging from 1 month to 52 months, all survivors are asymptomatic. Based on echocardiography, heart catheterization, and angiography, there are no stenoses and no shunts, and the atrial dimensions are good. Based on the results achieved with these surgical techniques, we conclude that most atrial lesions, anomalous pulmonary venous returns, and anomalous systemic venous returns are correctable at the time of orthotopic transplantation and do not preclude a successful outcome in children. PMID- 1898180 TI - Expanding applicability of transplantation after multiple prior palliative procedures. The Paediatric Heart Transplant Group. AB - The number of heart transplantations performed over the past 3 years has plateaued. However, the number of pediatric transplantations continues to slowly increase. Unlike adult heart transplantation, for which cardiomyopathy remains the most frequent indication, structural congenital heart disease is the primary indication in children. This report reviews our experience with orthotopic heart transplantation in the presence of structural congenital heart disease with and without prior palliative repair. The diagnoses included transposition of the great arteries, common atrium, left superior vena cava with and without a bridging innominate vein, dextrocardia, and univentricular configurations. The palliative repairs included Blalock-Taussig shunt, bilateral Glenn shunt, Fontan repair, and Mustard and Rastelli procedure. There were no early deaths. Two rejection-related late deaths have occurred at 8 months and at 3 years postoperatively. Extended use of donor tissue and modifications to surgical technique allowed for successful orthotopic heart transplantation in these patients who had structural congenital heart disease with and without prior surgical palliation. PMID- 1898181 TI - [The efficacy of the combined preparation ampicillin/sulbactam (Unasyn) in treating postoperative suppurative complications in a surgical hospital]. PMID- 1898182 TI - [The combined preparation ampicillin/sulbactam (Unasyn) in the general surgical clinic]. PMID- 1898183 TI - [The clinical and bacteriological efficacy of the combined preparation ampicillin/sulbactam (Unasyn) in treating different infections]. PMID- 1898184 TI - [The use of ampicillin/sulbactam (Unasyn) in treating inflammatory urological diseases]. AB - Unasyn is a combination of ampicillin, a bactericidal antibiotic, and sulbactam, an inhibitor of beta-lactamases. It was used in treatment of 36 patients with urogenital infections. The combination was administered intravenously and in the main intramuscularly. The treatment course amounted to 7-10 days. The average daily dose was 6 to 9 g. 22 patients with acute nonocclusive pyelonephritis were treated with the combination and its clinical and bacteriological efficacy was stated in 95 per cent of the cases. An excellent clinical effect of the combination was observed in 6 patients with acute epididymitis. A clinical improvement was also observed in the treatment of the patients with acute prostatitis and chronic renal infections. Unasyn proved to be a highly efficient antibacterial combination with regard to gram-positive flora and colon bacilli as representatives of gram-negative organisms. Satisfactory results were also stated in the treatment of infections caused by Proteus spp. Complete elimination of the pathogen was achieved in 57.7 per cent of the cases. No adverse reactions to Unasyn except pain in the site of the injection were recorded. PMID- 1898186 TI - [The dynamics of 2',5'-oligoadenylate synthetase activity in the nuclear and cytoplasmic fractions of human fibroblasts treated by double-stranded RNAs, by their complexes with DEAE-dextran and by type-I recombinant interferons. The ratio of double-stranded RNA-activated and -nonactivated froms of the enzyme]. AB - Novel original preparations of double-stranded RNAs (dsRNAs), i.e. larifan, ridostin and rifastin, and recombinant alpha 2- and beta-interferons promising for the clinical use were studied. The size and morphology of the dsRNAs in the preparation composition, the dynamics of their induction of interferon and the antiviral state in human fibroblasts and the effect of the DEAE dextran polycation on the activity of the dsRNAs were specified. For the first time the dynamics of 2',5'-oligoadenylate synthetase activity in the nuclei and cytoplasm of the human fibroblasts treated with the dsRNAs of different origin and their complexes with DEAE dextran was defined. To elucidate the specific features of the mechanism of antiviral action of dsRNAs and interferon, the relation of the 2',5'-oligoadenylate synthetase activity to dsRNAs was investigated. In the cells treated with dsRNAs and DEAE dextran there were an early activation of the enzyme and predominance of the enzyme activated forms requiring no addition of poly I.poly C to the reaction mixture. The results were indicative of possible intracellular activation of its isoforms, similar to that in the cells treated with interferon and contaminated with viruses. All the tested preparations of dsRNAs and interferons induced an increase in the activity of 2',5' oligoadenylate synthetase both in the cytoplasm and the nuclei of human fibroblasts. The same ability was observed in DEAE dextran which is likely to be one of the causes of the increase in dsRNAs antiviral activity under its effect. PMID- 1898185 TI - [The use of the combined preparation ampicillin/sulbactam (Unasyn) in the therapy of puerperal endometritis]. PMID- 1898188 TI - [A multifactorial analysis of the combined action of an antibiotic and a low molecular immunomodulator of microbial origin in experimental plague infection]. AB - The combined effect of doxycycline and a low molecular weight immunomodulator of microbial origin was studied in experimental plague infection with mathematical design of the experiment. Synergism of the action of the antibiotic and immunomodulator used in subtherapeutic doses was observed. The action was the most pronounced when the drugs were applied therapeutically. On the basis of the multifactorial analysis the regimens for the use of the antibiotic and immunomodulator were optimized. PMID- 1898187 TI - [The suppression of cellular Na+/H+ exchange leads to the inhibition of influenza virus activity]. AB - It was shown that amiloride, orthovanade and uabain induced almost a two-fold decrease in the rate of incubation medium oxidation by the chick embryo fibroblasts due to the Na+/H+ exchange and inhibited by more than 95 per cent the influenza virus activity. The following mechanism for inhibition of the influenza virus multiplication in the cells under the effect of the above mentioned substances was proposed: suppression of the cellular Na+/H+ exchange responsible for the decrease in pH value in the virus-carrying endosomes----prevention of the decrease in the intraendosomal pH value to the critical level----blocking of the acid dependent process of the virus uncoating----inhibition of the influenza infection as a whole. PMID- 1898189 TI - [The antibiotic prophylaxis of postoperative complications in breast cancer patients]. AB - The studies showed that infectious complications in patients operated for breast cancer (BC) most frequently developed after removal of the drainage tube resulting in poorer discharge favourable for development of infections. The causative agents in such cases are usually exogenous bacteria differing from endogenous ones (Staphylococcus epidermidis) inhabiting the human skin and sometimes contaminating the operative field. The endogenous bacteria are detectable bacteriologically in 60 per cent of the cases. Still, since the operation wound contains humoral and tissue immunity factors (specifically active against the host microflora) such bacteria rarely grow on artificial media (18 per cent) and even more rarely cause infections. Therefore, to prevent postoperative infections in patients with BC it should be recognized rational to use broad-spectrum antibacterial drugs such as ampiox, ampicillin, doxycycline, cephalosporins of the 2nd and 3rd generations, etc. for 5 to 6 days after the drainage removal. If an infection develops the preventive therapy should be replaced by an adequate therapy in accordance with the pathogen sensitivity. PMID- 1898190 TI - [The antibacterial therapy of suppurative-septic diseases against a background of kidney failure]. PMID- 1898191 TI - [The comparative pharmacokinetics of ceftriaxone in the blood and bronchial secretion in patients with different durations in the course of chronic bronchitis]. AB - The study on ceftriaxone penetration into bronchial secretion showed that in patients with a short-term history of chronic bronchitis (no more than 3 years) ceftriaxone used in a dose of 1 g once a day intramuscularly was detectable in the bronchial secretion within 10 hours after the administration, its concentrations being 0.67-2.41 micrograms/ml in 3 hours, 15.87 micrograms/ml in 4.5 hours, 4.58 micrograms/ml in 6.5 hours and 2.29 micrograms/ml in 10 hours. In patients with a long-term history of chronic bronchitis (mean 10 to 20 years) the presence of ceftriaxone in the bronchial secretion was detectable in a concentration of 0.51-3.75 micrograms/ml only in 2 hours after its administration. Beginning from the 5th hour after the administration its detection failed. This is indicative of lower ceftriaxone penetration into the bronchial secretion of such patients. The duration of chronic bronchitis did not influence ceftriaxone pharmacokinetics in blood. The contents of the antibiotic in serum and bronchial secretion were determined by HPLC (the resolving power of 0.5 micrograms/ml). PMID- 1898192 TI - [Beta-lactamase distribution among pathogenic microorganisms. The antibacterial action of a combined preparation of ampicillin/sulbactam (Unasyn)]. PMID- 1898194 TI - Notice of plagiarism. PMID- 1898193 TI - [A laboratory and clinical trial of the combined preparation ampicillin/sulbactam]. PMID- 1898195 TI - [Non-surgical repair of atrial septal defect by "buttoned" double disk device in children. First results in 3 children]. AB - Transcatheter closure of ostium secundum atrial septal defect (ASD) with a "buttoned" double-disk device was attempted in 5 children aged 14 months to 12 years, with success in 3 cases. The diameter of the ASD was 15 to 20 mm. The occluding devices were chosen with sizes 12-15 mm greater than those of the ASDs. There were no operative complications: the ASD was practically completely occluded in 2 children and left a very small shunt in a third case. Those three patients are doing well, 8 to 9 months after the procedure. In the other two cases, the device fell into the right atrium and had to be removed surgically without any complications. The "buttoned" double-disk device seems to be relatively simple and easy to insert through an 8F catheter. Additional technical improvements should enable more complete occlusion of ASD and easier retrieval by the transvenous route when incorrectly inserted. Further experimental and clinical studies are required to assess the results and to compare them with those of the other teams. PMID- 1898196 TI - [Aortic valve insufficiency: an unrecognized complication of the surgical repair of ostium primum atrial septal defect]. AB - Between 1974 and 1989, eight children undergoing surgical repair of a partial atrioventricular canal comprising an ostium primum atrial septal defect, mitral regurgitation due to a cleft mitral valve (6 cases) and a small ventricular septal defect (1 case) developed aortic regurgitation. This complication was diagnosed on the finding of a diastolic murmur 1 day to 9 years after the repair of the atrial septal defect. The degree of regurgitation was Grade I in 4 cases but in the other patients it was severe from the outset requiring emergency surgery the next day (1 case), or moderate at the beginning but rapidly progressive (1 case) or slowly progressive (2 cases) leading to aortic valvuloplasty in these 3 patients. The cause of the regurgitation was iatrogenic: perforation of the non coronary cusp secondary to repair of the ostium primum atrial septal defect. None of the patients required aortic valve replacement. After surgical valvuloplasty, all children had Grade 1 aortic regurgitation. Color coded Doppler echocardiography confirmed the diagnosis and helped assess the clinical course of this lesion during follow-up. PMID- 1898197 TI - [Research of gene(s) involved in situs inversus. Initial results]. AB - Reverse Genetics consists in identifying the gene responsible for a hereditary condition, the biochemical mechanism of which is unknown. We have applied this approach to families recruited according to the following criteria: 1) at least two members of the family must be affected; 2) one of the two subjects must have an abnormality of thoracic and/or abdominal lateralization. This abnormality of situs can form part of a syndrome: asplesia, polysplenia, heterotaxia, dextrocardia, situs inversus, Kartagener' or Ivemark's syndrome; 3) the other affected subject(s) must have some form of congenital heart disease and/or one of the phenotypes above described in 2); 4) in consanguinous marriages, only one child fulfilling the criteria in 2) above described is required. Eight families conforming to the above criteria are presented; lymphocytic transformation was successful in 90% of cases when the blood sample was received within 48 hours. The segregation of the alleles is in favour of a linkage between the tested probe and the syndrome(s) studied. In order to identify the gene responsible, we will have to increase the number of families studied and extend our research to sporadic cases. PMID- 1898198 TI - [Right pulmonary artery arising from the proximal ascending aorta. A model of reflex pulmonary hypertension of the left lung?]. AB - The right pulmonary artery arising from the proximal ascending aorta is a rare and severe malformation. This retrospective study of 11 children with this condition was undertaken to determine the conditions of diagnosis, to analyse the results of surgery, and, above all, to clarify the mechanism of the left pulmonary arterial hypertension which was always present. Ten of these patients were 4 to 90 days old. All had severe congestive cardiac failure with iso- or suprasystemic left pulmonary arterial hypertension. The only associated lesions were ventricular septal defect (1 case) and patent ductus arteriosus (7 cases). None of the patients had significant left-to-right shunts and only one had left atrial hypertension: this patient died before surgery could be performed. The other 9 patients underwent surgical correction and the pulmonary pressures immediately fell to normal or almost normal values. The child with the ventricular septal defect died of infection 6 weeks after surgery. The 8 survivors are doing well 1 month to 12 years later and left pulmonary pressures are normal in all, including those (5 cases) with a stenosed (4 cases) or completely occluded right pulmonary arterial circulation (1 case) and in 1 patient with obstructive vascular disease. The eleventh patient was very different: she had no signs or symptoms until 2 years of age, when a right pulmonary obstructive arterial disease but with normal left pulmonary pressures was documented. She was not operated on and remains well nine years later.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1898199 TI - [Holter monitoring, exercise test and atropine test in isolated congenital atrioventricular block in children]. AB - Twenty-four patients with isolated congenital heart block were investigated by 24 hour Holter monitoring at an average age of 9.3 +/- 5.5 years. Six patients were symptomatic and 18 were asymptomatic. Eight asymptomatic patients underwent exercise stress tests and an atropine test was performed in 10 asymptomatic patients to evaluate the capacity to accelerate the heart rate. The symptomatic patients were older than the asymptomatic patients. None of the parameters which analyse ventricular rate were significantly different in the two groups of patients. Significant ventricular arrhythmias (Lown Grade 2 or over) were recorded in 1 symptomatic and 3 asymptomatic patients. The incidence of these ventricular arrhythmias increased with age and degree of bradycardia. The percentage increase in ventricular rate after atropine correlated with what was observed on effort (r = 0.95, p = 0.01) but there was no relationship between the ventricular rates during these two tests and those recorded on Holter monitoring. The results of this series of children with isolated congenital heart block show the Holter parameters cannot distinguish symptomatic from asymptomatic patients. The exercise stress and atropine tests gave very similar results but their prognostic value has not yet been established. PMID- 1898200 TI - [Surgery without catheterization of aortic coarctation in newborn infants and infants under 3 years of age]. AB - A retrospective study of 150 children under 3 months of age who underwent repair of coarctation of the aorta in the same center (between 1972 and 1987) was undertaken to assess the problems posed by surgery without cardiac catheterisation or angiography. The patients were divided into two groups: Group A, comprising 104 children operated after invasive investigations, and Group B, comprising 46 children operated on Doppler echocardiographic data alone. The two populations were comparable and "hypoplastic aortic arch" type coarctation was present in over 60% of cases. However, there were more ventricular septal defects in Group B (67.5%) than in Group A (49%). There were no significant diagnostic errors in Group B (one case of interrupted aortic arch diagnosed at surgery). The 1 month survival was the same in the two groups (82%). The indications of pulmonary artery banding were less frequent in Group B although there were more ventricular septal defects in these patients. These results confirm the value of Doppler echocardiography in the context of urgent surgery of congenital heart disease. PMID- 1898201 TI - [Neonatal anatomical repair of transposition of great vessels associated with atrial septal defect. Apropos of 42 cases]. AB - The good results obtained by anatomic correction of simple transposition of the great arteries (TGA) in the neonatal period have incited some surgical teams to widen the indications to neonates with TGA associated with ventricular septal defect (VSD). The classical management of these patients is a two stage procedure: banding of the pulmonary artery followed by detransposition, which carries a certain risk. Between January 1985 and June 1990, 42 neonates with TGA and VSD underwent a combined procedure consisting in anatomic correction of the TGA and closure of the VSD. The average age of these patients was 16 days, and the average weight was 3.3 kg. Ten patients had coarctation and 6 underwent a complete one stage correction by an anterior approach. The surgical technique consisted in closing the VSD from the right atrium in 20 patients, from the right ventricle in 11 patients and from the pulmonary artery in 11 patients, associated with detransposition of the great arteries and coronary artery reimplantation. Three children died in the preoperative period (7.1%). In two cases, death was related to malposition of the coronary artery. The third fatality was the result of haemorrhage. There has been one late death three years after surgery. Four patients have been reoperated for stenosis of the right ventricular outflow tract (1 case), recurrence of coarctation (2 cases) and stenosis of the superior vena cava (1 case) and have survived. All patients were followed up for an average period of 26.4 +/- 19 months. They are all in the NYHA Class I without treatment. One patient has mild aortic regurgitation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1898203 TI - [Evaluation of the quality of life in adulthood of 158 patients surgically treated for tetralogy of Fallot]. AB - Open heart correction of tetralogy of Fallot is now carried out in infancy. This operation provides children with the best physical and mental conditions for them to complete their education. Until recently, follow-up had been too short to assess the results of repair during infancy in adults. The object of this study was to evaluate the quality of adult life in the first 158 survivors of this surgery, now aged 19 to 36 years, performed in our department since 1968. Ninety eight per cent of these patients are physically capable of leading a normal life; 24% obtained their "baccalaureate" and hold positions of high professional responsibility; 37% achieved basic education diplomas. Even those who left school without qualifications were usually able to find employment. The number of unemployed is less than that of the same age group in the general population. Thirty per cent are married or live with someone, and twenty five per cent have normal healthy children. The large majority have normal active lives. Thirty per cent play sport regularly as a leisure activity. Notwithstanding, all these patients were operated for severe symptoms. Two thirds had had previous Blalock shunts. Severe and persistent cyanosis is not a sign of anatomic severity of tetralogy of Fallot and does not seem to influence the socio-professional outcome. These results are those of what was considered to be high risk surgery at the time because of the inaccuracy of angiographic diagnosis, the inadequacy of myocardial protection and the chronicity of the anatomo-pathological lesions (average age of operated patients was 8 years).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1898202 TI - [Complete repair of tetralogy of Fallot in infants under the age of 6 months. Apropos of 25 cases]. AB - Between January 1982 and October 1988, 25 infants with Tetralogy of Fallot underwent total correction, total primary repair was carried out in 22 cases; 3 underwent correction after a palliative anastomosis. The average age was 3.7 +/- 1.6 months; the average weight was 5.06 +/- 1.41 kg and average body surface area was 0.30 +/- 0.06 m2. Nineteen patients had a regular anatomic form and 6 had an irregular form of the condition. The hospital mortality was 8% (2 cases): the mortality was nil in the regular anatomic form but 33% in the irregular anatomic forms. Twenty-one patients have been followed up for an average of 50.8 +/- 19.2 months. There were no late deaths; two patients were reoperated for a residual pulmonary stenosis; 19 patients are well and asymptomatic. Doppler echocardiography shows a residual pressure gradient between the right ventricule and pulmonary artery of 17.8 +/- 22.7 mmHg associated with a grade 1-2/4 pulmonary regurgitation. There are no residual ventricular septal defects or cases of atrioventricular block requiring permanent pacing. PMID- 1898204 TI - [Immediate and mid-term results of complete repair of truncus arteriosus during the first year of life]. AB - Twenty five infants with truncus arteriosus underwent complete surgical correction in the first year of life between January 1984 and June 1990 at Marie Lannelongue Hospital. All had cardiac failure and pulmonary hypertension. Another severe cardiac malformation was present in 6 cases. Complete repair was carried out under cardiopulmonary bypass with moderate hypothermia. After closing the ventricular septal defect the continuity of the right ventricle and pulmonary artery was reestablished by a valved Dacron conduit with a bioprosthesis (13 patients), by an autologous pericardial conduit with the same type of prosthesis (5 patients), by a valveless conduit (1 patient) or by direct insertion of the pulmonary artery (6 patients). Eight children (32%) died shortly after surgery. Seventy one per cent of children operated in the first month of life died compared with only 17% of those operated after one month of life (p less than 0.05). The seventeen survivors have been followed up for an average of 21 +/- 22 months. Three secondary deaths were observed at 33 days, 2 and 10 months after surgery: the first child died of left ventricular failure and pulmonary vascular disease related to the complexity of the associated cardiac malformations; the other 2 deaths were unexpected. The one and three year survival rate is 54%. Pulmonary stenosis with a systolic pressure gradient of more than 30 mmHg was found in 7 patients of whom 6 had valved Dacron conduits (p less than 0.01). One child was successfully operated 60 months after the total correction and another child is on the waiting list for reoperation 69 months after the total correction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1898205 TI - [Cavo-bipulmonary anastomosis. Apropos of 3 cases]. AB - Cavo-bipulmonary anastomosis (CBPA) in an anastomosis between the superior vena cava and the right pulmonary artery in continuity with the left pulmonary artery. This shunt is used in complex cyanotic congenital heart disease with pulmonary stenosis. It is the first stage of a total cavo-pulmonary shunt (TCPS). Thirty patients underwent this procedure at Laennec Hospital between April 1988 and April 1990. The surgical indications were retained when TCPS appeared to be too risky, mainly because of the associated malformations, the correction of which was performed at the same time. There were to early deaths; one patient was lost to follow-up and 27 patients have been followed up for an average period of 12 +/ 6 months. The surgical result was judged according to the degree of cyanosis; a poor result was defined as systemic saturation of less than 75% and a haematocrit of over 55%. One child died 5 months after surgery; there were 16 good results and 10 poor results. Seven patients were reoperated to carry out the second stage of the TCPS. The average gain in saturation was 9.7% in our series. Analysis of the patients who died or who had poor surgical results showed an anatomic cause in 11 of the 13 cases (pulmonary arteriovenous fistula, stenosis of the branches of the pulmonary artery, regurgitation of an atrioventricular valve) or a physiopathological cause (mean pulmonary artery pressure greater than 20 mmHg, or ventricular failure). The CBPA is a palliative procedure to reduce ventricular load, repair stenosis of the right pulmonary artery and to prepare the patient for a total cavopulmonary shunt. PMID- 1898206 TI - [Valvotomy and congenital aortic valve stenosis. Long-term results]. AB - Twenty nine patients (average age 11 years) underwent valvotomy for congenital valvular aortic stenosis from 1967 to 1983. The medium and long-term results were analysed retrospectively: 14 children have been reoperated; 11 for restenosis and 3 for aortic regurgitation after an average period of 11 years. Thirteen of the other 15 patients have been regularly followed-up for about 10 years: there are 7 good results, 3 average results and 3 restenoses. One patient was lost to follow up after 9 years and the other patient died secondarily of a non-cardiac cause. This series was compared to a previous one of 35 cases of valvular aortic stenosis who underwent valvotomy between 1954 and 1964. There were 6 deaths in the perioperative period and 6 during follow-up (on average 11 years after surgery), including 3 sudden deaths. Eleven patients were reoperated: 2 for endocarditis, 5 for restenosis and 4 for aortic regurgitation (on average after 13 years). Three patients were lost to follow-up and there are 9 survivors who have not been reoperated (average follow-up 27 years): 5 of these patients were reexamined; there were 2 excellent results, 2 average results and 1 restenosis. These results show that conservative surgery of congenital valvular aortic stenosis is now a low risk procedure in children, but it is a palliative solution. The main problem is that of follow-up to detect restenosis because of the risk of sudden death. This follow-up is much easier since the introduction of Doppler echocardiography, eventually associated with exercise stress testing in doubtful cases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1898207 TI - [Interrupted aortic arch. A series of 15 patients]. AB - Between 1983 and 1989, 15 children underwent surgical repair of interrupted aortic arch at 1 to 20 days of age. The anatomical form was a Celoria and Patton type B in all patients with an associated perimembranous ventricular septal defect in all but one who had multiple ventricular septal defects, and patent ductus arteriosus. Six children had a retro-esophageal right subclavian artery, two had subaortic stenosis and two had a right-sided descending thoracic aorta. In two children with severe hypoplasia of the ascending aorta the repair was performed in one stage with two deaths due to left ventricular failure. In the other B cases, a two-stage repair was carried out. The reconstruction of the aortic arch varied according to the individual case. All children had pulmonary artery banding. Seven children survived longer than 30 days. Six of them later underwent a complete repair. The only survivors were those patients in whom the neo-aortic arch grew harmoniously. The authors conclude that: a two-stage repair gave disappointing results in this series of consecutive patients, mainly because of the poor quality of the reconstruction of the aortic arch by thoracotomy. PMID- 1898208 TI - [Idiopathic dilated cardiomyopathies in children. Development and prognostic factors]. AB - This review is a retrospective study of the cases of 103 patients under 20 years of age with idiopathic dilated cardiomyopathy and represents the whole experience of the Department of Paediatric Cardiology of the Hospital of Cardiovascular Disease, Lyon, between January 1970 and December 1988. The aetiological investigations were constantly negative: hypertrophic, restrictive and secondary cardiomyopathies were excluded. The clinical, radiological, electrocardiographic and echocardiographic data of each patient was noted at the time of admission and at the end of the clinical course. There were many more infants in this series. The onset of the disease was usually sudden. All patients were given medical treatment. The study period ranged over 19 years. Forty one patients (39.8%) died mainly of terminal cardiac failure. Sixty two patients are still alive, of whom 39 are completely cured, 2 have undergone cardiac transplantation, and 21 have a variable degree of chronic invalidity. The six months survival was 77.5%; the 1 year survival was 70% and the 5 year survival was 60%. Over one third of deaths (36.6%) occurred during the first month, 56% during the first 3 months and 70% during the first year. A statistical analysis comparing the initial criteria to death by the chi 2 test revealed the following prognostic factors: age at presentation (32.9% of deaths in patients under 2 years of age compared to 56.6% in the group over 2 years of age, p less than 0.025) and a family history of myocardial disease. The other clinical, radiological and echocardiographic parameters had no predictive value in this series and it was not possible to identify potential candidates for cardiac transplantation. PMID- 1898209 TI - [Additional contribution of high amplification electrocardiography in the follow up of children with muscular dystrophy]. AB - Fifteen children and adolescents with muscular dystrophy underwent investigation by Doppler echocardiography and high amplification electrocardiography to evaluate the quality of left ventricular function. High amplification ECG showed minor intra-atrial conduction defects in 3 cases and abnormal late micro potentials without arrhythmogenic late potentials in 3 other cases. Significant abnormalities were observed in 40% of children examined. Doppler echocardiography showed relative conservation of systolic left ventricular function but a decrease in indices of contractility was observed in 46% of cases, especially in patients with Duchenne muscular dystrophy. Abnormalities of left ventricular distensibility were observed earlier and were more common (53% of cases). A significant decrease in cardiac output was found in 50% of patients, especially among the older and more severely affected children irrespective of the type of muscular dystrophy. These two investigations provide complementary information for the evaluation of left ventricular function of children with muscular dystrophy and they are proposed routinely for the follow-up of these patients. PMID- 1898210 TI - [Transient myocardial ischemia and isolated congenital mitral valve prolapse in an infant]. AB - The investigation of a cardiac murmur in a 9 month old infant led to the clinical, echo and angiographic diagnosis of congenital mitral regurgitation due to isolated mitral valve prolapse, whereas the electrocardiogram showed signs of inferior myocardial ischaemia which regressed in a week. The valvular dysfunction of mitral valve prolapse has been held responsible for coronary spasm ischaemia and infarction in adults. This complication has not been previously reported to our knowledge in infancy. PMID- 1898211 TI - [Diagnosis of the mechanism of reciprocating tachycardia by a simplified electrophysiological study]. AB - The authors attempted to identify the parameters which best differentiated intranodal reentry from tachycardias associated with an accessory pathway during a simplified electrophysiological study. The data were obtained by using two catheters, one recording right atrial activity and the other delivering programmed stimulation in the right ventricle. Sixty-four patients in whom the mechanism of their tachycardias had previously been determined were studied. There were 19 intranodal and 45 accessory pathway tachycardias. The following parameters were studied: the ventriculo-atrial interval during tachycardia; the prematurity of atrial activity in response to programmed ventricular stimulation; the shortest ventriculo-atrial interval when the atrial activity was premature; the difference between the shortest ventriculo-atrial interval with atrial prematurity and the ventriculo-atrial interval during tachycardia; in the absence of prematurity the ventriculo-atrial interval with the shortest ventricular coupling was used. The ventriculo-atrial interval during tachycardia was shorter in intranodal reentry (43 ms vs 170 ms, p less than 0.001). This interval was greater than 120 ms only in accessory pathway tachycardias and was only under 75 ms in patients with intranodal tachycardias. Premature atrial activation was observed in 42% of intranodal and 98% of accessory pathway tachycardias (p less than 0.001). The predictive value for tachycardias involving an accessory pathway was 85% when the auriculogramme was premature and, conversely, it was 92% for intranodal tachycardia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1898212 TI - [Mid-term results of heart valve replacement with 2 types of pericardial heterograft. Apropos of 208 cases]. AB - Medium-term results of valve replacement with a pericardial bioprosthesis were analysed in 141 patients receiving an Ionescu-Shiley aortic prosthesis and in 67 patients receiving a Mitroflow aortic (42), mitral (21) or double mitro-aortic (4) bioprostheses. There were 8 deaths in the operative (5.7%) and medium term (56 months) follow-up periods in the Ionescu group and a cumulative survival of 625 patient-years. There were 16 late deaths, 8 of cardiac origin. The 8 year survival and good functional results rates were 71% and 53% respectively. The linear rates of thrombo-embolism, endocarditis, reoperation, valvular dysfunction and regurgitation were 3.5, 1.1, 2.6, 2.7 and 6.1% patient-years. The corresponding figures in the Mitroflow bioprostheses were 0.5, 1.0, 3.1, 3.1 and 5.6% patient-years, but the average follow-up was shorter (36 months) with a cumulative survival of 195 patient-years. These results underline the frequency of primary valve dysfunction the mechanisms of which are: early tear in areas of high mechanical stress and late calcification. However, the hemodynamic profiles of this type of prosthesis are better than those of porcine bioprostheses which make them a valuable alternative in elderly patients operated for calcific aortic stenosis with a small aortic ring. PMID- 1898213 TI - [Value of the association of blood cardioplegia and energetic warm reperfusion in cardiac transplantation]. AB - Blood cardioplegia at 8 degrees C results in cardiac standstill whilst maintaining minimal metabolic functions of the cardiac cell. Reinjection every 20 minutes allows cellular reoxygenation, the delivery of essential elements (Tham, CPD), and the elimination of products of myocardial degradation accumulated during ischemia. Before declamping the aorta, a reperfusion with warm blood (34 degrees C) containing glutamate and GTN enables restocking of the energy reserves (Krebs' cycle) and a lowering of coronary and systemic resistances. This technique used systematically if even more effective when the ischemic time is prolonged as is the case in cardiac transplantation. The 50 transplants performed since January 1989 with this form of myocardial protection were compared with 50 procedures performed in 1988 with crystalloid cardioplegia. There was no significant difference in the duration of ischemia or of cardiopulmonary bypass between the two groups. Patients benefitting from blood cardioplegia defibrillated spontaneously more frequently, required lower doses of Dopamine for shorter periods and were extubated earlier. PMID- 1898214 TI - [Diagnosis of coronary artery disease by thallium 201 myocardial scintigraphy during atrial pacing]. AB - Rapid atrial pacing may reveal myocardial ischemia but the sensitivity for the diagnosis of coronary artery disease is not high enough for routine use. Therefore, the value of atrial pacing coupled with Thallium 201 scintigraphy was evaluated. Sixty-two patients (53 men and 9 women) referred for investigation of angina or chest pain were divided into two groups: a control group of 13 patients (9 men and 4 women, average age: 57.1 years) with insignificant coronary lesions (less than 50%) (N = 5) or normal coronary angiography (N = 8), and a group of 49 patients (44 men and 5 women, average age: 55.5 years) 27 of whom had a history of myocardial infarction (17 posterior, 10 anterior). Coronary angiography showed single vessel disease in 44.9% of cases, double vessel disease in 34.7% and triple vessel disease in 18.4% of cases, and 1 patient with left main stem disease. All 62 patients underwent the same study protocol which comprised: incremental atrial pacing (to the calculated maximal heart rate), Thallium 201 myocardial scintigraphy immediately after pacing and during the redistribution phase, and coronary angiography. The sensitivities of anginal pain (36.7%) and ECG changes during atrial pacing (57.1%) were too low for the diagnosis of myocardial ischemia. On the other hand, Thallium 201 scintigraphy with atrial pacing was more sensitive (87.8%) and specific (84.6%) for coronary artery disease. Stenosis of the left anterior descending artery was diagnosed with a sensitivity of 96.4% and that of the right coronary artery with a sensitivity of 90.9%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1898216 TI - [Results of programmed ventricular stimulation in induced non-sustained polymorphic ventricular tachycardia and maintenance of stimulation]. AB - Programmed ventricular stimulation risks inducing non-pathological ventricular fibrillo-flutter. The aim of this study was to determine if the induction of a non-sustained polymorphic ventricular tachycardia (over 5 intraventricular reentries) could prevent this incident. One hundred and thirty-three non sustained polymorphic tachycardias were induced by 2 or 3 extrastimuli during 1450 programmed ventricular stimulation studies. Ventricular stimulation was continued and led to ventricular fibrillo-flutter in 46 cases (Group I); to induction of sustained ventricular tachycardia in 26 cases (Group II) or to no other arrhythmias excepting the non-sustained tachycardia in 61 cases (Group III). The duration of the salvo was similar in all 3 groups. The rate of the induced arrhythmia was significantly lower in Group II (234 vs 290/min). The essential difference between the three groups was the clinical context. Only patients in Group II had previously documented sustained ventricular tachycardia and only patients in Group III had no apparent underlying cardiac disease. These results suggest that the decision to stop programmed ventricular stimulation should be based on the clinical indications of the study. In patients with previously documented or probable sustained ventricular tachycardia, it would seem to be necessary to continue ventricular stimulation irrespective to the rate and duration of the induced non-sustained ventricular tachycardia. PMID- 1898215 TI - [Causes of failure analysis after cardiac transplantation. From a consecutive series of 91 cases]. AB - Ninety-three cardiac transplantations were carried out in 91 patients (2 retransplantations) between March 1st 1987 and November 1st 1989, in 84 adults and 7 children under 15 years of age. The indications were dilated cardiomyopathy (48%), ischemic cardiomyopathy (35%), decompensated valvular heart disease (11%), congenital heart disease (3%) and two cases of Uhl's anomaly. Twelve patients underwent transplantation after external circulatory assistance (13%), 11 patients after inscription on the list of extreme emergencies, and 68 on an elective basis (74%). The postoperative immunosuppressive protocol was triple therapy: Ciclosporine, Azathioprine and Prednisone. Three of the children died. The early adult mortality was 9 cases (10.7%). It was 8% in patients operated electively. Major infectious complications occurred in 10 patients (11%). Rejection was looked for by systematic endomyocardial biopsy and echocardiography. Three hundred and forty-nine biopsies were made. Thirty-five patients (44%) had no problems of rejection. Seventy-nine patients have now been followed up for an average of 19 months. There were 7 late deaths. Seventy seven per cent of the survivors are asymptomatic. Acute rejection and transplant dysfunction were the two main causes of early mortality after cardiac transplantation. Although the long-term prognosis is uncertain, the medium-term results are very encouraging. PMID- 1898217 TI - [Late coronary reperfusion. A possible etiology of post-infarction angina]. AB - Late recanalisation of the infarct Related Artery is possible and may cause post infarction angina. This was observed in 7 male patients who had complete occlusions of an artery with collateral circulation in the immediate post infarction period. After a symptom-free period of 17 months, angina recurred and repeat angiography showed recanalisation of the occluded artery with regression of the collateral circulation resulting in myocardial ischemia. Myocardial revascularisation was then required. PMID- 1898218 TI - [Efficacy and tolerance of disopyramide in arrhythmia associated with sinus node dysfunction]. AB - The aim of this study was to assess the effect of delayed release Disopyramide 500 mg daily on sinus node function in 12 subjects with sinus node dysfunction and supraventricular and/or ventricular excitability. An ECG, Holter monitoring and electrophysiological studies of sinus node function with an oesophageal electrode were performed before and after 5 days treatment. The drug had to be discontinued in 1 patient because of urinary retention. The Disopyramide suppressed the clinical tachyarrhythmias in 8 out of the 11 subjects. The maximal sinus pause observed on Holter monitoring did not change significantly. It only increased in one subject. The mean sinus cycle length during electrophysiological study slightly decreased but there was a global increase in sinoatrial conduction time from 309 +/- 164 to 413 +/- 125 msec and of the corrected sinus mode recovery time from 470 +/- 168 to 605 +/- 303 msec. However, these changes were not significant. This study of delayed released Disopyramide shows a discordance between the tendency for sinus node function to deteriorate when assessed by electrophysiological studies and good clinical tolerance as assessed by Holter monitoring in the bradycardia-tachycardia syndrome. PMID- 1898219 TI - [Computerized analysis of ST segment during exercise. Interpretation of "saw tooth" appearance]. AB - The authors report original appearances (sinusoid or "saw tooth" aspect) of computerised analysis of the ST segment in 3 cases, corresponding to ST changes during exercise stress testing. This is due to alternating ST elevation and depression probably related to abnormal vasomotor tone given the fact that the recording was normalised by coronary vasodilator therapy. PMID- 1898220 TI - [Demonstration of abnormalities of myocardial mitochondrial oxygenation in cardiac graft rejection]. AB - Abnormalities of myocardial metabolism during acute rejection may be due to ischemia to primary metabolic changes related to rejection. An experimental study of heterotopic cardiac transplantation in the rat was undertaken to study myocardial mitochondrial oxidation during acute rejection. The receivers were Lewis rats and the donors Fischer (FL: allograft) or Lewis (LL: isograft) rats. The oxygen consumption of the mitochondria (VO2m) isolated from the transplanted and native hearts was measured by oxygraphy six days after transplantation. Using maleate and glutamate substrates, the VO2m of transplanted hearts was significantly lower than that of native hearts in the two groups of rats (FL, p less than 0.01; LL, p less than 0.01). In addition, the VO2m of FL allograft transplanted hearts was significantly lower than in the LL rats (30 +/- 9 vs 100 +/- 15 nanoatoms of oxygen/min.mg/prot, p less than 0.01) as was the VO2m of the native hearts (FL: 106 +/- 23 vs LL: 164 +/- 26, p less than 0.02). The respiratory control ratio (RCR) was significantly lower in the transplanted than in the native hearts in both the FL and LL groups (p less than 0.05 and p less than 0.01 respectively). The comparison of the RCR in the two groups (FL vs LL) showed no significant difference for transplanted or native hearts. Electron microscopy of transplanted (rejected or not) and native hearts showed no morphological abnormality of the mitochondria. The lower VO2m of the allograft group indicates a disturbance in the mitochondrial respiratory pathway during acute rejection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1898221 TI - [Severe ischemic ventricular arrhythmia during dipyridamole scintigraphy]. AB - A case of severe myocardial ischaemia complicated by syncopal ventricular tachycardia during injection of Dipyridamole for stress Thallium myocardial scintigraphy in a coronary patient is reported. Myocardial ischaemia (chest pain, ECG changes) is classically rare (30% of cases) and usually benign during Dipyridamole injection, and either regress spontaneously or after administration of Theophylline. However, the possibility of serious complications such as this justifies the same criteria of strict surveillance as for classical exercise stress testing. PMID- 1898222 TI - [Hydatid cyst of the right ventricle]. AB - A 35 years old women has had palpitations for the last six months on auscultation she has a mid systolic clic. The echocardiogram shows a typical aspect of right ventricular hydatid cyst. The right and left catheterization confirms the diagnosis. A thoracic scan is done to rule out other localisations. The patient is successfully operated. The authors emphasized the importance of an echocardiogram in a visceral or secondary localisation of echinococcosis. PMID- 1898223 TI - [Ostial stenosis of the left main coronary artery after mediastinal radiotherapy. Apropos of a case]. AB - Coronary artery disease (CAD) is a well-known complication of mediastinal irradiation. We report a case of subocclusive ostial stenosis of the left main coronary artery, in a 27 years old man, who had been irradiated 14 years before for a stage 4 Hodgkin's disease. Among the 68 reported cases of CAD attributed to radiotherapy, 11 involved an ostial stenosis of either right coronary artery, or left main coronary artery or both. Thus mediastinal irradiation seems to be a definite cause of ostial coronary artery stenosis; several types of myocardial revascularization have been suggested for this kind of CAD. PMID- 1898224 TI - [Development and evaluation of a laser catheter with tip fiberoptic for coronary angioplasty]. AB - A fiber-optic tip catheter has been developed for treating coronary and peripheral atherosclerosis percutaneously. The catheter is coupled to an ionised Argon laser emitting at an optical power of 1 to 7 Watts. It is designed to follow a guide wire and to perform tissue ablation by a new concept combining the effects of central vaporisation and peripheral thermal remodelling of the obstructed artery. This mode of function should considerably reduce the risks of false route previously encountered with laser angioplasty. The optical and thermic properties of the catheter prototypes were determined by physical methods. These experiments showed that the temperature of the metallic component of the catheter tip did not exceed 30 degrees C at a continuous power of 6 laser Watts when the flush was functioning. It attained 400 degrees C in the absence of the flush. The performances of the catheter were then tested in a number of in vitro experiments. First of all, the catheter tip was placed perpendicularly to atheromatous cadaver aortae to study the effect of vaporisation with respect to the laser power. The threshold of vaporisation was 1 Watt (irradiance: 1100 Watts/cm2). The catheter was then introduced into plastic tubes obstructed by atheromatous plaques. This experiment demonstrated the mechanical solidity of the catheter and its flexibility in difficult operating conditions: diameter 2mm, 45 degrees angles, irregular calcified plaques. It also showed that the optimal safety-efficacy laser power was 3 laser Watts and that the exposure times varied with respect to the nature of the plaques tested.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1898225 TI - Localized phosphorus 31 magnetic resonance spectroscopy in chronic schizophrenic patients and normal controls. PMID- 1898226 TI - Gastric collision tumor (carcinoid and adenocarcinoma) with gastritis cystica profunda. AB - We report a rare case of gastric collision tumor (carcinoid and adenocarcinoma) with gastritis cystica profunda that developed in a 49-year-old Japanese man. Early gastric cancer (moderately differentiated tubular adenocarcinoma) was present at the edge of an ulcer in the posterior wall of the upper gastric body. In addition, a carcinoid tumor was found adjacent to adenocarcinoma. This tumor displayed ribbonlike or trabecular patterns, and numerous constituent cells were positive for the argyrophil reaction with Grimelius' stain and serotonin. Electron microscopic features of this tumor confirmed typical carcinoid. There was no merged appearance between both tumors, suggesting collision-type tumor. PMID- 1898227 TI - How to build a computer-assisted, diagnosis-finding system. An example in dermatopathology. AB - We present a computer-assisted, diagnosis-finding system based on the simple stochastic approach of Bayes; this system was realized in a standard database architecture and run on DOS personal computers. The expert knowledge in the form of specified morphologic criteria was keyed in by means of pull-down menus or downloaded if the system was linked with a reporting system according to the dBASE (Ashton-Tate, Inc, Torrance, Calif) database standard. We present a simple example in dermatopathology but the system shell can also be used for applications in other fields of pathology. This article is not restricted to general remarks about computer-assisted diagnosis finding. The compiled program and the easily comprehensible and well-documented program listings in the CLIPPER (Nantucket Corp, Los Angeles, Calif) or DOS language is available on request. PMID- 1898228 TI - Colorectal smooth-muscle tumors. A pathobiologic study with immunohistochemistry and histomorphometry. AB - Smooth-muscle tumors are an interesting group of tumors that show considerable site specificity in their pathobiology. Recent work has also shown that some previously so-called smooth-muscle tumors were not, in fact, truly leiomyogenic, hence the origin of the more embracing term stromal tumors. The purpose of this retrospective study was to delineate the tumor subsets constituting colorectal stromal tumors, and to determine the histopathologic correlates for biologic aggressiveness for these tumors. The cohort was constituted of 12 patients; the mean follow-up was 6.6 years with a median of 5.0 years. Immunohistochemical evaluations showed tumoral positivity for muscle-specific actin (12 of 12), vimentin (11 of 12), desmin (two of 12), and S100 protein (zero of 12). Electron microscopic examinations corroborated this leiomyogenicity profile (five of five). Semiquantitative histomorphometric analysis showed that tumor size, cellularity, mitoses, and necrosis, in that order, correlated with biologic aggressiveness. The immunohistochemistry results for this cohort of colorectal stromal tumors vindicated the traditional histochemical evaluations in that all tumors showed features of leiomyogenicity. For colorectal smooth-muscle tumors, tumor size appears to be the best predictor for biologic aggressiveness. This study reinforces the concept of site-specificity for smooth-muscle tumors. PMID- 1898229 TI - Origin of so-called mesothelioma of the atrioventricular node. An immunohistochemical study. AB - To determine the origin of a mesothelioma of the atrioventricular node, immunohistochemical studies that used various antibodies, including the antibody against mesothelial cells, were performed on a mesothelioma of the atrioventricular node in a case. The lining cells of the tubules that composed the tumor were negative when tested with anti-mesothelial cell antibodies. Carcinoembryonic antigen was negative, but the secretory component was positive. Serotonin and calcitonin were positive in a few cells. We concluded that a mesothelial origin was unlikely, and it was suggested that the tumor was of an entodermal origin. PMID- 1898230 TI - An immunohistochemical study of benign clear cell ('sugar') tumor of the lung. AB - Benign clear cell ("sugar") tumor is a rare and most unusual pulmonary neoplasm. Although several reports in the literature have focused on the ultrastructural features of benign clear cell tumor, only a few cases have been formally studied by immunochemistry. Using a broad panel of polyclonal and monoclonal antibodies, five cases were evaluated. In all five cases, there was diffuse immunoreactivity for cathepsin B. Four cases showed immunoreactivity for HMB-45 and for alpha 1 antitrypsin. By two different sources for antivimentin, there was immunoreactivity in four cases (Biogenex, Dublin, Calif) and in two cases (DAKO, Santa Barbara, Calif), respectively. Additional immunoreactivity was present for S100 protein (three cases), HAM-56 (two cases), factor XIIIA (two cases), and neuron-specific enolase (one case). No case expressed immunoreactivity for keratin (AE 1, AE 3, or CAM 5.2), carcinoembryonic antigen, chromogranin, synaptophysin, glial fibrillary acidic protein, or alpha 1-antichymotrypsin. This immunochemical profile suggests that HMB-45, in combination with a variety of immunostains, may serve to distinguish benign clear cell tumor from other clear cell neoplasms. PMID- 1898232 TI - Kaposi's sarcoma of spleen with unusual clinical and histologic features. AB - We report a case of Kaposi's sarcoma in a young woman who presented with unusual clinical and histologic features. The unusual clinical features were the absence of cutaneous lesions; the presence of a splenic mass; and extensive involvement of the peritoneum, resulting in massive ascites and intestinal and ureteral obstruction. We postulate that the spleen was the primary site of the tumor. The unusual histologic features were the presence of both sclerotic and cavernous hemangioma variants in the same tumor and extensive areas of calcium deposits in the tumor. Such atypical clinical and histologic features can pose diagnostic difficulties for both clinicians and pathologists. PMID- 1898231 TI - Angiotropic large-cell lymphoma in a patient with adrenal insufficiency. AB - Angiotropic large-cell lymphoma is a rare disorder characterized by a proliferation of malignant lymphoid cells within the lumina of small vessels. The skin and central nervous system are typically affected; however, involvement of other organs has been described. We document an unusual case of this disorder in a patient who suffered clinically significant adrenal insufficiency and subsequently died. Autopsy disclosed angiotropic large-cell lymphoma involving both adrenal glands. PMID- 1898233 TI - Hurthle cell hyperplasia and sarcoidosis of the thyroid. AB - We report of a case of Hurthle cell hyperplasia of the thyroid that was correctly identified preoperatively by fine-needle aspiration cytology but was unexpectedly associated with sarcoid granulomas. To our knowledge, the association has not been previously reported. The rarely described thyroid involvement by sarcoidosis is briefly reviewed. PMID- 1898234 TI - Pleomorphic fibroma of skin. A case report and immunohistochemical study. AB - An immunohistochemical study of a clinically benin but cytologically atypical mesenchymal lesion of the skin is presented. This lesion has been previously reported as pleomorphic fibroma and was shown to follow a benign course with a potential for local recurrence. These lesions contain occasional markedly atypical enlarged spindle cells with anaplastic-appearing nuclei. Nonmirror image mitotic figures may be present. Histogenesis of this neoplasm remains controversial with a fibroblastic origin being favored by previous authors. Our immunohistochemical findings would support this conclusion. PMID- 1898235 TI - Carcinosarcoma of bladder following long-term cyclophosphamide therapy. AB - Since the advent of long-term cyclophosphamide therapy, an association between this agent and the subsequent development of bladder neoplasms has been documented. Only six sarcomas have been reported, to our knowledge. This report describes the first case in which a leiomyosarcoma and an invasive transitional cell carcinoma (ie, carcinosarcoma) developed in a patient with non-Hodgkin's lymphoma treated with 240 g of cyclophosphamide over a 6.5-year period. PMID- 1898236 TI - Massive cardiac involvement of adult T-cell leukemia/lymphoma. An autopsy case. AB - We describe an unusual autopsy case of adult T-cell leukemia/lymphoma with massive cardiac involvement. The patient was admitted to the hospital with symptoms of fever and cervical lymph node enlargement, which improved following treatment with vincristine sulfate, cyclophosphamide (Endoxan), prednisolone sodium succinate, and doxorubicin hydrochloride (Adriamycin). He was then followed up in the outpatient clinic, but was readmitted to the hospital with palpitations and dyspnea. Cardiomegaly developed rapidly, and the patient died of congestive heart failure 3 months after readmission. The heart was massively enlarged at autopsy. The heart, including adhered surrounding tissue, weighed 1600 g. The myocardium was found to be replaced by massive infiltration of atypical lymphoid cells. Cardiac involvement by adult T-cell leukemia/lymphoma may result from extension or retrograde flow through cardiac lymphatics from the destroyed mediastinal lymphatic system. PMID- 1898237 TI - Retroperitoneal bronchogenic cyst presenting as an adrenal mass. AB - Subdiaphragmatic bronchogenic cysts are rare, and those located retroperitoneally are exceptional. A review of the English-language literature revealed only three reported cases. We describe an additional case of a retroperitoneal bronchogenic cyst that presented uniquely as a symptomatic adrenal mass and discuss the cases of subdiaphragmatic bronchogenic cysts reported in the English-language literature. PMID- 1898238 TI - Mesonephric rest hyperplasia. A potential diagnostic pitfall. AB - A case of mesonephric rest hyperplasia, an incidental finding in the hysterectomy specimen of a 48-year-old woman, was initially misdiagnosed as a well differentiated cervical adenocarcinoma. We highlight the histologic, histochemical, and immunohistochemical features of this potential diagnostic pitfall and review the relevant literature. PMID- 1898239 TI - Inflammatory pseudotumor of the spleen. Morphological, radiological, immunophenotypic, and ultrastructural features. AB - A case of inflammatory pseudotumor of the spleen is described. Its rapid enlargement, demonstrable by ultrasound studies and computed tomographic scan, its gross appearance, and some of its histologic features suggested malignant lymphoma. However, a characteristic circumferential zonal pattern and polytypic immunophenotype helped to establish the correct diagnosis. In retrospect, the zonal pattern was also identified radiologically. PMID- 1898240 TI - A rare case of 'coccidioidoma' of the breast. AB - Coccidioidomycosis has been reported in almost every tissue of the human body. The gastrointestinal tract and breast have been uniquely spared from this fungal infection. Despite the exceedingly large number of screening mammographies that are performed every year, to our knowledge subcutaneous breast tissue involvement as the sole presentation or of secondary spread of coccidioidomycosis has not been reported. We describe a patient who showed an unusual manifestation of a coccidioidal breast nodule simulating a neoplasm. The patient had been transiently immunosuppressed by prednisone therapy for presumptive temporal arteritis. PMID- 1898243 TI - Plastic embedding of unfixed tissues following freeze substitution. PMID- 1898242 TI - Intraluminal crystalloids in follicular adenoma of the thyroid. PMID- 1898244 TI - Intralaboratory performance and laboratorians' expectations for stat turnaround times. A College of American Pathologists Q-Probes study of four cerebrospinal fluid determinations. AB - More than 400 laboratories participated in the module of the College of American Pathologists' quality assurance program, Q-Probes, which measured intralaboratory turnaround time (TAT) of stat cerebrospinal fluid tests. Four determinations encompassing more than 14,000 specimens were monitored and intralaboratory TATs were compared with participants' TAT goals. The median TATs were as follows: cell count, 32 minutes; glucose, 34 minutes; protein, 37 minutes; and Gram's stain, 45 minutes. Between 14% and 21% of participants (test dependent) met their goals 100% of the time, with 72% of the determinations completed within the time laboratorians required. Standard statistical stepwise regression analysis was used to model influence of up to eight factors on TAT. Correlations were test and bed-size dependent, but ranged from a high of .23 to a low of .02. Only computerized reporting and instrumentation measuring protein and glucose had a consistent effect, delaying TAT, whereas use of a stat laboratory, one workstation, automation, computerized order entry, and centralized processing gave variable results. We conclude that laboratorian goals for cerebrospinal fluid test TAT are met most of the time, and that a stepwise regression analysis poorly explains factors that statistically influence TAT. PMID- 1898241 TI - In situ oncocytic change in association with multiple renal cell adenocarcinomas. AB - We report a case of in situ oncocytic change in association with two low-grade renal cell adenocarcinomas and one contralateral low-grade oncocytic adenocarcinoma. The in situ oncocytic change showed abundant cytoplasmic mitochondria confirmed by ultrastructural examination and phosphotungstic acid hemotoxylin staining. In addition, this in situ oncocytic change expressed cytokeratin CAM 5.2 in the absence of cytokeratin AE1/AE3, as reported in oncocytic renal cell adenocarcinomas. Further study of in situ oncocytic change identified in kidneys resected for adenocarcinomas with regard to follow-up and management of the contralateral kidney seems indicated. PMID- 1898245 TI - Genetic analysis of the Duchenne muscular dystrophy gene. AB - Molecular biology techniques have changed the way in which we now consider a patient with Duchenne muscular dystrophy or Becker muscular dystrophy. Using cDNA probes, it has been shown that approximately 65% of the patients with Duchenne muscular dystrophy or Becker muscular dystrophy have gene deletions. The identification of a deletion allows the disease to be confirmed by noninvasive DNA testing. Furthermore, the identification of the gene defect can help distinguish Becker muscular dystrophy from other clinically similar neuromuscular disorders. Most importantly, the elucidation of the gene defects has resulted in the application of direct carrier and prenatal diagnostics. PMID- 1898246 TI - Studies on observer variation. Should the rules be changed? PMID- 1898247 TI - HLA-DR expression on the microvasculature of portal tracts in idiopathic portal hypertension. Immunohistochemical characteristics and relation to portal phlebosclerosis. AB - We recently reported that HLA-DR antigen was expressed on the microvasculature of portal tracts more frequently in idiopathic portal hypertension (IPH) than in normal livers or in other hepatic diseases, and that this HLA-DR expression may be involved in the development of the portal venopathy characteristic of IPH. The present study was performed to evaluate the relationship between the HLA-DR expression and portal tract lesions, as well as to investigate the immunohistochemical characteristics of the HLA-DR-positive microvasculature using liver wedge biopsy specimens obtained from 32 patients with IPH. According to the degree of phlebosclerosis of the portal veins, the portal tracts were divided into three groups: mild, moderate, and severe. The microvasculature in portal tracts was positive for HLA-DR in 21 (66%) of the 32 specimens and in 133 (44%) of 302 portal tracts. In the 21 specimens, there was no significant difference in the prevalence of HLA-DR-positive microvasculature among the three groups: it occurred in 57 (66%) of 86 portal tracts in the mild group, 53 (61%) of 87 portal tracts in the moderate group, and 23 (49%) of 47 portal tracts in the severe group. The HLA-DR-positive microvasculature was positive for type IV collagen and receptors of Ulex europaeus lectin I, suggesting that HLA-DR-positive microvessels are blood vessels. These findings suggest that HLA-DR antigen is already expressed on portal microvessels in the incipient stage of IPH, and that HLA-DR expression persists during the progression of portal phlebosclerosis. The HLA-DR expression may be an initiating factor leading to immunologic assault on portal microvessels in IPH. PMID- 1898248 TI - Effectiveness of histopathological diagnoses in dysfunction of hepatic transplantation. Review of 146 histopathological studies from 53 transplants. AB - In 47 patients who underwent 53 liver transplantations and immunosuppression with cyclosporine (cyclosporin A), methylprednisolone sodium succinate, and antithymocyte globulin, 146 histopathological studies were performed (138 biopsies, six hepatectomies, and two autopsies). The following microscopical diagnoses were made: 43 acute rejections (29.4%), six chronic rejections (4.1%), 18 liver blood perfusion changes (12.3%), 15 biliary changes (10.2%), 10 cases of functional cholestasis (6.8%), two drug reactions (1.3%), two hepatitis B virus recurrences (1.3%), 11 opportunistic viral infections (7.5%), 18 minimal changes (12.3%), two nonclassifiable changes (1.3%), and 19 plurietiological changes (13%). A histopathological diagnosis of acute rejection was made in 31 transplants (58.4%). In 22 (71%) of them, acute rejection was diagnosed with the protocol biopsy specimen that was obtained during the second posttransplant week. Leukocyte counts and serum bilirubin and enzyme levels were obtained on the same day that the hepatic biopsy specimens were taken. There was no significant statistical difference between the mean serum data that accompanied each histopathological diagnosis, allowing identification of a characteristic biochemical profile for the causes of graft dysfunction. We report a detailed description of the microscopical findings of each diagnosis and the following conclusions: (1) Acute rejection is the most frequent cause of hepatic dysfunction and has an early appearance during the posttransplant period. (2) Histopathological findings can identify the causes of the dysfunction. (3) There is no specific biochemical pattern to differentiate these causes. This may be due to the frequent combination of etiological factors in every dysfunction episode. PMID- 1898249 TI - Tegretol excipient-induced allergy. PMID- 1898250 TI - Apneic oxygenation in apnea tests. PMID- 1898251 TI - Circadian variation in stroke. PMID- 1898252 TI - Perception of affect in patients with dementia of the Alzheimer type. AB - The ability to perceive affect was examined in 19 patients with Alzheimer's disease and in 19 control subjects. Nine tasks were given. All participants were asked to recognize facial emotion, to provide verbal labels of facial emotion, and to identify emotion portrayed in drawings or in verbal descriptions of emotional situations. The results indicate that there are significant differences between patients with Alzheimer's disease and control subjects on all of the tasks. However, when test scores were adjusted for the cognitive abilities of the subjects, few of the tests continue to differentiate the groups. These results suggest that the deficits of patients with Alzheimer's disease on perception of affect tasks are likely to be the result of their cognitive defects and not the result of a primary impairment in the perception of emotion. PMID- 1898253 TI - Altered serotonergic and cholinergic synaptic markers in Pick's disease. AB - Choline acetyltransferase and acetylcholinesterase activities as well as serotonin and imipramine binding were determined in the hypothalamus, nucleus basalis of Meynert, and frontal and temporal poles of subjects with Pick's disease. Choline acetyltransferase activity was decreased in the hypothalamus and nucleus basalis of Meynert, and acetylcholinesterase activity was decreased in the nucleus basalis of Meynert only. Serotonin binding was decreased in all sites but the nucleus basalis of Meynert, and imipramine binding was altered only in the frontal pole. Comparison with previous reports of Alzheimer's disease indicates that with respect to these synaptic markers, Alzheimer's disease and Pick's disease are not similar. PMID- 1898254 TI - Diagnostic criteria for multiple sclerosis research involving multiply affected families. AB - Existing diagnostic criteria for multiple sclerosis present significant limitations when assessing multiplex families for three reasons: (1) restricting age of onset to 10 to 50 years is likely to exclude 10% of patients known to have a later onset, (2) diagnoses based on subjective information can potentially result in a false-positive diagnosis, and (3) including progressive myelopathies occurring within families, particularly when highly symmetrical, may result in the improper inclusion of genetically determined neurological diseases such as familial spastic paraparesis. The validity of any molecular genetic approach for determining disease susceptibility critically depends on diagnostic accuracy. We present adapted diagnostic criteria that address each of these diagnostic pitfalls unique to multiplex multiple sclerosis family research. PMID- 1898255 TI - Multiple sclerosis associated with vitamin B12 deficiency. AB - We describe 10 patients with a previously unreported, to our knowledge, association of multiple sclerosis and unusual vitamin B12 deficiency. The clinical features and the age at presentation were typical of multiple sclerosis, with eight cases occurring before age 40 years, which is a rare age for vitamin B12 deficiency. Nine patients had hematologic abnormalities, but only two were anemic. All six patients examined had low erythrocyte cobalamin levels. Only two patients had pernicious anemia; in the remaining patients the vitamin B12 deficiency was unexplained. A vitamin B12 binding and/or transport is suspected. The nature of the association of multiple sclerosis and vitamin B12 deficiency is unclear but is likely to be more than coincidental. Further studies of vitamin B12 metabolism, binding, and transport in multiple sclerosis are indicated, as these cases may offer a clue to the understanding of a still mysterious neurologic disorder. PMID- 1898256 TI - Implantation of human fetal ventral mesencephalon to the right caudate nucleus in advanced Parkinson's disease. AB - Disaggregated ventral mesencephalic tissue from single aborted human fetuses of 11 to 18 weeks' gestation was implanted stereotaxically into a consistent striatal site in 12 patients with advanced Parkinson's disease. All were receiving optimum levodopa therapy and were examined preoperatively and at 3,6,9, and 12 months postoperatively. Immunosuppression was not used. There were significant sustained improvements at 12 months in three patients; motor fluctuations were absent in two. There were modest group improvements up to 6 months, with increased quality of "on" and "off" phases, quantity of on times, and specific improvements in contralateral upper limb bradykinesia. Preoperative levodopa requirements were reduced to a mean of 64% at 6 months and 61% at 12 months. Deterioration below baseline ratings occurred in three of nine patients who had consistent follow-up to 12 months. Grafting of midgestational human fetal tissue can lead to improvement in Parkinson's disease. Individual disease severity may be critical, and further trials are needed to identify host factors influencing outcome. PMID- 1898257 TI - Borrelia rhombencephalomyelopathy. AB - Three patients, in whom the diagnosis of Borrelia burgdorferi infection was unknown for several years, developed a biphasic involvement of the central nervous system: an acute brain-stem dysfunction was followed up, in two patients, by a progressive, disabling myelitis and, in one patient, by further relapsing remitting episodes of severe multifocal rhombencephalitis. The most consistent cerebrospinal fluid abnormalities in the analysis of sequential specimens were elevated total IgM levels that normalized after penicillin therapy. The neuropathologic findings in one patient showed microgliosis and meningovascular involvement of the central nervous system, resulting in two ischemic infarcts in the myelencephalon. Few spirochetes were localized in the leptomeninges and around subependymal vessels of the fourth ventricle. The vascular element consisted of an obliterative inflammatory vasculopathy in the medullary parenchyma. This study (1) provides pathologic evidence that a vascular disease induced by B burgdorferi is a pathogenetic mechanism for cerebrovascular diseases, and (2) emphasizes the similarities between neuroborreliosis and neurosyphilis. PMID- 1898258 TI - Cerebrospinal fluid interleukins, immunoglobulins, and fibronectin in neuroborreliosis. AB - Intrathecal synthesis of IgM and IgG, oligoclonal immunoglobulin bands, and the levels of fibronectin, soluble interleukin 2 receptor, interleukin 6, and tumor necrosis factor alpha were investigated with the use of enzyme-linked immunosorbent assay in 46 paired cerebrospinal fluid and serum samples from 32 patients with meningopolyradiculoneuritis due to Borrelia burgdorferi (Lyme borreliosis stage 2). Cerebrospinal fluid and serum interleukin 6, although not specific for neuroborreliosis, were good indicators of disease activity, while the serum soluble interleukin 2 receptor level was only mildly elevated. Tumor necrosis factor alpha was never detected in cerebrospinal fluid or serum specimens, and cerebrospinal fluid IgM, IgM index, and cerebrospinal fluid IgM/cerebrospinal fluid IgG ratios were significantly higher than in all other neuroimmunologic disorders evaluated and may be valuable diagnostic indicators for neuroborreliosis. The estimation of intrathecally synthesized IgG and IgM fractions for the differential diagnosis of neuroimmunologic disorders did not add to IgG and IgM index calculations. PMID- 1898259 TI - Clinical implications of seizures in neurosarcoidosis. AB - Seizures are a recognized manifestation of neurosarcoidosis, but their clinical relevance is not well established. We reviewed the characteristics, clinical correlations, and prognosis of seizures in 79 patients with neurosarcoidosis. Thirteen (15%) of the 79 patients had seizures, and in eight patients (10%) a seizure was the first manifestation of neurosarcoidosis. These seizures were generalized tonic-clonic seizures in 12 patients (92%) and partial seizures in four patients (31%). The patients with neurosarcoidosis with seizures were more likely to have a progressive or relapsing clinical course and intracranial mass lesions (four patients [31%]), encephalopathy or vasculopathy (eight patients [62%]), or hydrocephalus (five patients [38%]). These central nervous system disorders, rather than the seizures per se, were responsible for most of the serious morbidity and the two deaths (15%) among our patients with seizures. Indeed seizure control was good in 11 (85%) of 13 patients treated with combinations of steroids and antiepileptic medications. Seizures are an important sign in neurosarcoidosis because they are associated with more severe and progressive or relapsing forms of central nervous system sarcoidosis and may be an early manifestation of such disorders. PMID- 1898260 TI - Myasthenia gravis in childhood and infancy. Usefulness of electrophysiologic studies. AB - The diagnostic yield of electrodiagnostic tests was evaluated in 21 children with myasthenia gravis (MG). Twelve children had juvenile autoimmune MG, four had neonatal MG, four had congenital MG, and one had MG with arthrogryposis. Repetitive stimulation (RS) of the ulnar nerve was performed in every patient, sometimes with sensitization by ischemia. When the RS test was negative, the spinal or facial nerve was tested. In the group with neonatal MG, the RS test disclosed a significant decrement in 75% of the patients. Among the 17 other children, the overall percentage of positive RS tests was 88%. An ulnar nerve RS test was positive in 41% of them. Sensitization of ulnar nerve RS by ischemia improved the diagnostic yield to 66%. A spinal or facial nerve RS test was positive in seven of 10 patients. These results confirmed the diagnostic value of RS, with sensitization by ischemia, when necessary, in childhood MG whenever a careful technique is provided. PMID- 1898261 TI - Generalized cortical dysplasia. Clinical and pathologic aspects. AB - Three children with profound mental retardation and intractable seizures died at ages 10 months, 3 years, and 7 years, respectively. Complete examination of their brains showed generalized cortical dysplasia, without any major malformation of the external gyral pattern. The neuropathologic features of cortical dysplasia include abnormally thickened cortex with indistinct demarcation of the gray-white matter junction. In many areas, the cortex contained increased numbers of large neurons with disordered cortical lamination. Heterotopic neurons were scattered throughout the white matter with decreased myelination of the underlying white matter. To our knowledge, these cases represent the first fully detailed neuropathologic study of diffuse cortical dysplasia--a newly recognized entity of abnormal neuronal migration. PMID- 1898262 TI - Parkinson's disease in Ferrara, Italy, 1967 through 1987. AB - Epidemiological surveys on Parkinson's disease that have been carried out in different parts of the world have suggested that the disease is uniformly distributed in white populations. The position with regard to the Mediterranean peoples is still controversial, because of the large variation of the frequencies observed in the different areas that have been investigated. We therefore studied the frequency of Parkinson's disease in the Local Health Service of Ferrara, northeastern Italy (mean population, 187,000). Based on 394 patients, the mean incidence per year for the period from 1967 through 1987 was 10.01/100,000. The incidence rate of Parkinson's disease among cases with early onset was found to be statistically higher in rural areas as compared with urban ones (6.32/100,000 vs 3.11/100,000). Moreover, the study revealed a significantly higher incidence rate among agricultural workers (20.6/100,000). These results would seem to give further support to the hypothesis of a possible causal role of environmental factors that are mainly linked to agriculture, most likely due to the continual exposure to toxic agents in this area. However, further studies, which are not exclusively epidemiological, are necessary before any conclusions may be drawn, because many confounding variables may account for the results from surveys of this type. PMID- 1898263 TI - Kinetics of anti-peripheral nerve myelin antibody in patients with Guillain-Barre syndrome treated and not treated with plasmapheresis. AB - Serial anti-peripheral nerve myelin antibody titers were determined in 28 consecutive patients with Guillain-Barre syndrome during the course of their illness. Eighteen patients were treated with plasmapheresis and 10 were not. Anti peripheral nerve myelin antibody titers in the group treated with plasmapheresis declined significantly more rapidly than in the group not treated with plasmapheresis. Five patients treated with plasmapheresis who showed initial clinical improvement, with a concurrent decline in anti-peripheral nerve myelin antibody titer, had one or two recurrences of clinical symptoms during a 2- to 8 week period associated with an increase in anti-peripheral nerve myelin antibody titer. Recurrent weakness was severe enough to prompt additional courses of plasmapheresis. The data suggest that serial determinations of antiperipheral nerve myelin antibody in patients with Guillain-Barre syndrome may identify patients with antibody rebound associated with recurrence of clinical symptoms and prolonged recovery in whom further plasmapheresis should be considered. PMID- 1898264 TI - The coexistence of tics and dystonia. AB - We studied nine patients with motor and phonic tics and other features of Tourette's syndrome, who developed persistent dystonia in addition to their tics. All, except one, were males (mean age, 35.8 years; range, 8 to 59 years), and had onset of tics prior to age 18 years (mean age, 9 years; range, 1.5 to 17 years). None of the patients were treated with neuroleptic drugs prior to the onset of dystonia. Torticollis and blepharospasm were the most common forms of dystonia. Seven patients had a history of tics in first degree relatives. While these patients were seen in a specialized movement disorder clinic and may, therefore, represent a population with atypical and more severe symptoms, the high prevalence rate of dystonia (5.0% of all patients with Tourette's syndrome seen in the clinic) suggests that some patients with tics may have an increased risk for dystonia. PMID- 1898265 TI - Finger tremor after carbon disulfide-based pesticide exposures. AB - Index finger tremor accompanying voluntary movement was studied in 19 age-matched control subjects and in 19 grain industry employees chronically exposed to carbon disulfide-based fumigants. Visual judgments of tremor amplitude made by neurologists during clinical examinations equaled the sensitivity of computerized tremor amplitude measurements. Tremor frequency variations detectable only with computerized measurement were present in grain workers with and without increased tremor amplitudes. Frequency differences discriminated between normal subjects and 74% of the grain workers. The distribution of tremor frequency power in the grain workers was often sequestered at 5 to 7 Hz, reminiscent of tremor in idiopathic Parkinson's disease. These findings suggest that the measurement of subtle tremor frequency changes may provide an early indication of chronic carbon disulfide poisoning. PMID- 1898266 TI - Delayed postanoxic encephalopathy after strangulation. Serial neuroradiological and neurochemical studies. AB - A 13-year-old boy was the victim of attempted strangulation. His condition had returned to normal by the sixth day after the assault; however, from the seventh day, choreoathetosis, dystonia, and marked pseudobulbar paralysis developed in the boy. The computed tomographic scans and T2-weighted magnetic resonance images that were obtained at this time revealed low-density and high-signal intensities in the region of the bilateral putamen and caudate nucleus. These symptoms and the changes in his computed tomographic scans and magnetic resonance images subsided gradually during a 2-month period. Sequential analysis of the cerebrospinal fluid for gamma-aminobutyric acid and dopamine concentrations during his illness revealed reciprocal changes with normal recovery. Because of the delayed onset of neurological changes and the cerebrospinal fluid showing reversible symptoms, the delayed encephalopathy after strangulation had been related to the biochemical alterations that followed anoxia in the vulnerable basal ganglia. PMID- 1898267 TI - Polymyositis after ciguatera toxin exposure. AB - Biopsy-proved polymyositis subsequently developed in two patients who were severely poisoned by ciguatera fish toxin. Ciguatera toxin may have several mechanisms of action and may represent more than one toxin. The patients' clinical courses and the unlikelihood of coincidence of contracting both diseases suggested to us a causal relationship. Although we cannot prove this relationship, we suggest a mechanism by which the toxin predisposed the muscle to inflammation. PMID- 1898268 TI - Expression of epidermal growth factor mRNA in the developing mouse mandibular process. AB - Reverse transcription and cDNA amplification (polymerase chain reaction) of total RNA preparations were used to characterize the expression of EGF mRNA in the mandibular arch of day 9-17 mouse embryos. EGF mRNA was present in mandibles at day 9 and 10 but not at days 11-17. Separate RNA preparations from epithelium and mesenchyme at day 10 revealed EGF mRNA in both components. PMID- 1898269 TI - Tooth crown size in 46, X, i (Xq) human females. AB - Permanent tooth crown sizes of six Finnish females with a 46, X, i(Xq) chromosome constitution (isochromosome for the long arm of the X chromosome) were measured from dental casts and compared with those of normal women, first-degree female relatives and 45, X females. Crown diameters of the 46, X, i(Xq) females were not only smaller than in the normal women but even smaller than the 45, X females. These findings can be considered indirect evidence that X chromosome gene(s) for tooth crown growth are most probably located on the short arm. PMID- 1898271 TI - Relationship between calcium and inorganic phosphorus concentrations of both resting and stimulated saliva and dental plaque in children and young adults. AB - Calcium and inorganic phosphorus concentrations of both resting and paraffin-wax stimulated whole saliva and dental plaque were estimated in 39 young adults and 98 children aged 12-14 yr. Plaque was collected from the adults after 48 h without tooth-brushing and consumption of a standardized diet. Plaque was collected from the children without any dietary or oral hygiene restrictions. The results from the study with children provided consistent evidence for a statistically significant relationship between salivary and plaque concentrations of both calcium and inorganic phosphorus. However, multiple regression indicated that only the concentrations in the stimulated secretion were directly associated with concentrations in plaque. The apparent relationship between concentrations in resting saliva and plaque was due to correlation between resting and stimulated saliva. These relationships were less apparent in the young adults, in whom the controlled conditions resulted in a narrower range of mineral concentrations in dental plaque. PMID- 1898270 TI - Platelet aggregation induced by uncommon serotypes of Streptococcus sanguis isolated from patients with Behcet's disease. AB - Uncommon serotypes were tested for their ability to induce aggregation in platelet-rich plasma. Both uncommon and common serotypes induced platelet aggregation in rabbit platelet-rich plasma, but serotonin release was higher with the uncommon serotypes. Aggregation at ATP release varied between uncommon and common serotypes. With human platelet-rich plasma, only uncommon serotypes showed aggregation. Differences in serotype selectivity and the rate of aggregation were noted among platelet donors. About half of the patients with Behcet's disease and 30% of health controls showed platelet aggregation. Plasma from non-responder patients with Behcet's disease inhibited aggregation of healthy responder platelets within 20 min. Thus selective binding of uncommon serotypes of Strep. sanguis to platelets might cause the vasculitis in Behcet's disease. PMID- 1898272 TI - Motor-unit territory in the human masseter muscle. AB - Motor-unit territories in human masseter are reportedly focal and related to putative subvolumes of muscle. However, in the absence of a reliable method of locating needle-electrode recording sites within the muscle in three dimensions and due to inherent weaknesses in electromyographic recording techniques, the limits of motor-unit territory in the masseter may have been underestimated. Single motor-unit responses were recorded as time-locked events from 32 paired needle recording sites throughout the masseter muscles of three subjects. Recording sites were located stereotactically with an optical system, magnetic resonance imaging, and a common reference, then displayed graphically in three dimensions. The mean linear separation of the paired recording sites was 8.8 +/- 3.4 mm. The putative territories had a preferred orientation in the antero posterior axis. Motor-unit territories were larger than described previously and appeared to be related to anatomical compartments. The restriction of these territories to discrete regions of the muscle provides an anatomical substrate for selective regional motor control of the human masseter muscle. PMID- 1898273 TI - Relative growth of the human fetal skull in width, length and height. AB - Linear measurements of the width, length and height of the face and cranium were made on 60 fetuses of 49-212 mm crown-rump length. Absolute growth rate was derived from the slope of the regression line of dimensional length against time. There was a high correlation between absolute growth rate and mean dimensional length (r = 0.995; p less than 0.001). The relative growth rate was calculated by dividing the absolute growth rate by the mean dimensional length. Change in shape was measured by the relative increase or decrease in dimensional length once the outlines were normalized to an equal area to eliminate the effect of size. Change of shape correlated highly with relative growth rate (r = 0.95; p less than 0.001). Relative growth rates provide a reliable indication of change in shape, unlike absolute growth rates, which are mainly influenced by size. Measurement of relative growth rates showed an increase in cranial length greater than height greater than width and facial length greater than width greater than height. PMID- 1898274 TI - Effect of repeated oral administration of tobacco snuff on natural killer-cell activity in the rat. AB - The possible immune effect of oral snuff was investigated. In male adult rats, oral snuff given for 15 weeks significantly decreased NK-cell activity in peripheral blood against murine NK cell-sensitive target cells (YAC-1 lymphoma). PMID- 1898275 TI - Help your patients, your colleagues and yourself. A review of medical records. PMID- 1898276 TI - Avulsion of an isolated varicose vein. PMID- 1898278 TI - The kenspeckle figure. PMID- 1898277 TI - Patient education. Medications and diabetes. PMID- 1898279 TI - Summer and pseudomonas. PMID- 1898281 TI - Carpal tunnel syndrome. PMID- 1898280 TI - Pictorial essay. Alleged sexual assault. PMID- 1898282 TI - The role of diet in infant colic. PMID- 1898283 TI - Treatment of male sexual partners. PMID- 1898284 TI - The difficult ankle. AB - Ankle sprains are extremely common in sport and usually respond to conservative management, but many apparent ankle sprains do not respond to treatment and remain painful. Alternative diagnoses must be considered. These require careful clinical assessment and often further investigations. PMID- 1898285 TI - Tennis injuries. AB - An unfit tennis player is more likely to suffer an injury. The tennis player should be well prepared physically and possess a sound technique. Attention should be paid to playing gear to minimise the possibility of injury. PMID- 1898286 TI - Triathlon injuries. The swim-bike-run how-to for medical practitioners. AB - The triathlon is becoming one of the favourite pastimes of many of our patients. It carries with it a likelihood of overuse injuries. For most of these conditions, treatment will follow the usual regimens, but a good understanding of the mechanics and training principles will give any practitioner more options in the management of these patients. PMID- 1898287 TI - Hazards of alpine sport. AB - Alpine sports in Australia include downhill skiing, cross country skiing, snowboarding, snowmobiling and tobogganing. Despite a popular impression that the sport is risky the injury rate is low and there has been a large decrease in injuries relative to increased participation in the past 20 years. Nevertheless, more young skiers are sustaining injuries, many of which could be avoided. PMID- 1898288 TI - The little athlete. AB - Little athletes suffer a variety of injuries, either from accidents or overuse. Overuse injuries are related especially to pain syndromes in the legs, such as apophysitis and tendinitis. Areas of rapid growth are vulnerable to injury. It is important that 'little athletes' perform within limits set by their age and their body development and that they enjoy their sporting activities. PMID- 1898289 TI - Ocular and periocular infections. AB - In this article, the author emphasises the symptoms and signs of infections of the eye and their significance in establishing a diagnosis. Factors in the natural history and treatment that may modify the general practitioner's approach are indicated. Warning signs requiring immediate referral are highlighted. PMID- 1898290 TI - Medical work force changes. Implications for general practice in Victoria. AB - Annual surveys have supported claims that the medical work force has been increasing too rapidly and that the intake of Australian and foreign graduates should be reduced. The increase has led to changes in distribution, choice of vocation, style and work content. Female doctors have increased their working hours, are poorly represented in some specialties and are less likely than men to practice outside the metropolitan area. PMID- 1898291 TI - How valuable are patients' blood glucose monitoring results? AB - Blood glucose testing by people with diabetes is an accepted method of assessing diabetes control, and is often the basis for adjusting the diabetes treatment regimen. This case report illustrates the importance of checking the patient's testing technique when the home and surgery test results differ. PMID- 1898292 TI - Panel on deliberate G-induced loss of consciousness: introduction. AB - Over the last decade, G-induced loss of consciousness (G-LOC) has been recognized as a significant operational problem for pilots of high performance aircraft in both the U.S. Air Force and U.S. Navy. Consequently, government laboratories have initiated research studies to learn more about the G-LOC phenomenon in an attempt to reduce its hazards. Many of these studies require the occurrence of LOC during their conduct. For this reason, animal models have been developed to use in these studies. However, even though sophisticated animal models such as baboons can be taught to perform tasks before and after G-LOC has occurred, these models have deficiencies that can be overcome only by the use of human volunteers who willingly submit to G-LOC studies on the centrifuge. Such human G-LOC studies began in World War II and continue today. These studies are presently conducted without guidelines regarding subject selection, numbers of G-LOCs allowed per subject per unit time, restraint systems, or specific medical examinations required before, during, and after each episode of LOC, or after each completed study. This panel will discuss what is known about the pathophysiology of G-LOC, the limitations of animal models in these types of studies, the possible medical and psychological sequelae, and the legal implications of conducting deliberate G LOC research. We hope that the information developed by this panel will be useful to laboratory human-use review committees in determining the requirements and the nature of guidelines for conducting such studies. PMID- 1898293 TI - Physiologic bases of G-induced loss of consciousness (G-LOC). AB - Exposure of pilots to high sustained +Gz (head to feet) or rapid onset of +Gz can produce a variety of pathophysiologic effects ranging from the loss of peripheral vision to total blackout and, finally, G-induced loss of consciousness (G-LOC). A G-LOC research program divided into four phases has been organized at USAFSAM/Crew Technology Division. In contrast to previous studies in acceleration, this program will focus exclusively on the ultimate problem in G LOC; namely, inadequate cerebral perfusion leading to impaired brain energy metabolism, structure and function. The primary objective of this research program is to identify and arrange chronologically the numerous physiological and biochemical alterations in the brain that comprise the mechanism of G-LOC. PMID- 1898294 TI - Performance recovery following +Gz-induced loss of consciousness. AB - Seven male baboons (average weight, 20.6 kg) were trained in a simple shock avoidance performance task on the USAFSAM centrifuge. A red light was presented to the baboon at approximate 2-s intervals. The animal was allowed 1 s to turn off the light or receive a 1-s shock. The shock could be abbreviated by a late trigger pull. Thus, the animal could avoid, escape, or accept the full shock. EEG was monitored from three transcranial stainless steel electrodes. Loss of consciousness (LOC) was induced by a rapid onset (4 or 6/s) exposure to 8 +Gz and sustained until LOC was identified by a near isoelectric EEG signal. Performance recovery time was measured from the return of EEG activity to the time when the animal resumed the performance task. These data were compared with previously obtained human data and found to be very similar. Also, it was found that time of performance recovery became significantly shorter after multiple LOC exposures and the performance recovery time significantly increased with increased time of unconsciousness. This study demonstrates the utility of the baboon as an animal model for G-induced LOC (G-LOC) research. PMID- 1898295 TI - Medical considerations for human exposure to acceleration-induced loss of consciousness. AB - Unconsciousness in humans has probably been occurring since before recorded history. Acceleration-induced loss of consciousness (G-LOC) in flight has been occurring since 1919. Loss of consciousness and syncope are common occurrences in clinical medicine with G-LOC, occurring in a large number of aircrew and research subjects during centrifuge exposures. Although the major risk to humans exposed to centrifuge-induced G-LOC is related directly to the central nervous, cardiac, and musculoskeletal (neck and back) systems, other risks are also present. Human exposure to G-LOC is required to help solve the G-LOC problem in aviators. To perform such human research, the benefits must clearly outweigh the risks to the human. Even if the risk-benefit ratio is considered favorably balanced, continued monitoring of individuals exposed to G-LOC is mandatory. To facilitate monitoring of humans exposed to G-LOC, a central nervous system (CNS) insult classification system would be of significant value. A suggested classification scheme which considers the type of CNS insult, the history of exposure to G-LOC, and the temporal evolution of potential CNS insult is developed. To date there is no indication that G-LOC episodes have any associated long term or persistent psychophysiological sequelae. Improved acute and long term evaluation of humans exposed to G-LOC are, however, important aspects of conducting G-LOC research with humans. Such research and careful monitoring are necessary to understand and eventually solve the G-LOC problem in aviators. PMID- 1898296 TI - A review of central nervous system effects of G-induced loss of consciousness on volunteer subjects. AB - A review of the literature on the central nervous system (CNS) effects of repeated centrifuge acceleration studies involving G-induced loss of consciousness (G-LOC) reveals that remarkably few adverse effects have been reported, aside from the G-LOC itself, even in subjects with numerous exposures. However, most of the followup studies were performed before the availability of sophisticated neuropsychological tests and non-invasive means of imaging the CNS, such as computerized tomography (CT), magnetic resonance imaging (MRI), brain electrical activity measurement (BEAM), and positron emission tomography (PET). Further, only a handful of long-term followup studies have been done. Thus, although repeated G-LOC may have induced some long-term adverse CNS effects, either organic or functional, little has been done to detect them. Even granted that some damage may be done, this risk must be weighed against the risk of aviators of similar damage from high +Gz exposures in flight, and even more against the risk of fatal G-LOC aircraft accidents. Volunteers for centrifuge acceleration studies should be fully informed about what is known and not known in this regard. As an ancillary measure, head restraints may be useful in avoiding postural trauma to the cervical spine, or impact injury to the head when G-LOC occurs and the head snaps forward and down. PMID- 1898297 TI - Legal and ethical aspects of deliberate G-induced loss of consciousness experiments. AB - Informed consent is both a legal and accepted ethical prerequisite to nontherapeutic human experimentation. The informed consent obtained from the subject in G-LOC experimentation is in the same form as the risk disclosures used in high-G acceleration experiments. However, in high acceleration protocols G-LOC is a potential risk while in G-LOC experiments it is the result. The case law embodies three modern evidentiary standards (the "professional," "material fact," and "possible risks" tests) employed by common law courts when deciding whether the risk disclosures are sufficient to elicit the informed consent of the subject. Each standard is applied against the disclosures in the G-LOC protocol to determine if the elements of the requirement are met. The risk disclosures are wanting in specific identification under the three tests. The deficiency is the failure to inform the subject that G-LOC may result in a pathologic state of unconsciousness about which little is known. Without complete disclosure of this lacking state of medical knowledge, it is questionable whether informed consent can be given. If subjected to judicial scrutiny, the disclosures stated in the G LOC protocol used in government sponsored research will probably be found deficient. PMID- 1898298 TI - Panel summary: from Zen riddle to the razor's edge. AB - A summary of the Panel on Deliberate G-induced Loss of Consciousness reviews the global issue of rendering human subjects unconscious in the centrifuge as a research procedure. Major issues summarized are informed consent, a common taxonomy for G-LOC events, and medical surveillance of subjects made deliberately unconscious. PMID- 1898299 TI - Mapping of evoked magnetic field with visual stimulation: a secondary projection and processing area. AB - Visual evoked fields (VEFs) were measured in four subjects, using magnetoencephalography (MEG) and a flashed checkerboard pattern stimulation with a duration of 20 ms. The left hemisphere was searched for the primary and the secondary projection areas with a full-field stimulus. Typical VEFs were found in the occipital area, which is considered to be the primary projection; and a secondary projection area was found in the dorsal temporal area in all subjects. The negative VEF in the secondary projection area was robust and stable, with a range of latencies from 200 to 230 ms. The amplitude was more than -400 femtotesla (fT), as high as the VEF in the occipital area. However, we were unable to localize the position of a dipole, since only one amplitude maxima was found. PMID- 1898300 TI - Effects of acute aspartame and acute alcohol ingestion upon the cognitive performance of pilots. AB - Anecdotal evidence has associated the artificial sweetener aspartame with a number of symptoms of central nervous system (CNS) dysfunction. There are, however, little scientific data concerning the effect of aspartame upon complex mental operations such as those necessary for flying an aircraft. Thirteen pilots were tested in a double-blind study using the SPARTANS cognitive test battery of aviation-relevant information-processing tasks. These tasks relate to perceptual motor abilities, spatial abilities, working memory, attentional performance, risk taking, processing flexibility, planning and sequencing ability. Subjects were tested over five sessions consisting of pretest and posttest controls and three randomly ordered treatment sessions. The treatment conditions involved an aspartame dose of 50 mg/kg body weight, a placebo condition, and an ethyl alcohol (0.1% BAL) condition as the positive control. No detectable performance decrements were associated with the aspartame condition, although decrements in psychomotor and spatial abilities were detected in the ethanol condition. Results were found to be consistent with prior flight-simulator studies of alcohol, but do not appear to support the concerns expressed in anecdotal testimony regarding the deleterious effects of aspartame upon cognitive performance. PMID- 1898302 TI - Sleep patterns in aircrew operating on the polar route between Germany and east Asia. AB - The study was performed as the second part of an investigation to assess sleep behavior and circadian rhythmicity in aircrew operating regular passenger flights between Germany and East Asia via Anchorage (ANC). Continuous records of sleep and ratings of sleep quality were obtained by sleep logs from 101 B747-cockpit crewmembers, starting at least 3 d before commencing flight duty, continuing during days on duty (the duration depending on the flight schedule) and finishing 4 d after return, at the earliest. Regardless of the specific duty roster, sleep deficit occurred mainly after the first flight leg to ANC, presumably due to the 10-h time zone difference and the short layover time. During the layover in the Far East, the sleep deficit diminished partly because of additional naps. Sleep was often disturbed and scattered over days and nights. Another pronounced sleep deficit occurred after the first return flight from South Korea or Japan to ANC. Compared to the outgoing layover period in ANC, the number and duration of naps increased during this layover and, additionally, on the first 2 d after returning home. Poorer sleep quality ratings were associated with accumulated sleep deficit and increased napping, but significant decrements in sleep quality were seen only during two out of the six different duty rosters. All six of the polar route duty rosters may lead to significant sleep disturbances. During some flight schedules the sleep deficit is large enough to raise operational implications. PMID- 1898301 TI - Effects of temazepam on sleep, performance, and rhythmic 6-sulphatoxymelatonin and cortisol excretion after transmeridian travel. AB - The effects of 20-mg doses of the short-acting benzodiazepine, temazepam, on sleep, performance and pineal, adrenal and temperature rhythms were investigated in a placebo-controlled, double-blind crossover study. Ten healthy males were studied 4 d prior to flying from Sydney to London via Tokyo and Anchorage (11 time zones). Temazepam or placebo were administered at 2300 hours (local time) during the flight and for 4 d after arrival. After a 7-d recreation break in London, the subjects returned to Sydney via Moscow and Tokyo and again took five doses of temazepam or placebo. During the 5 d following their arrival in London or Sydney, the subjects collected urine, had rectal temperature monitored, performed a battery of performance tests and filled out questionnaires. Temazepam significantly improved various subjective sleep characteristics, particularly on the first few nights. Performance (choice reaction time, critical flicker fusion threshold and pencil and paper tests) was not impaired by temazepam treatment. The pineal rhythm was assessed by urinary 6-sulphatoxymelatonin excretion rate determinations. The time of peak 6-sulphatoxymelatonin excretion (acrophase) occurred progressively later each day after arrival in London and Sydney, however the rate of adjustment of the rhythm was not affected by temazepam. Similarly, the urinary cortisol and temperature rhythms adjusted to the new environments by progressive delay with no drug effect being evident. Administration of temazepam clearly had a beneficial effect on sleep and alertness following transmeridian travel, without detrimental effects on performance. There was no evidence to suggest that temazepam altered the rates of entrainment of physiological rhythms to the new environments. PMID- 1898303 TI - The development of pursuit tracking skills. AB - This article examines the development of the visual-motor skill of pursuit tracking. Parameters studied include tracking error and emotional tension, as manifested in heart rate and strength of grip exerted on the control handle used in the task. A specially developed device converted grip strength into an electrical signal suitable for analysis. Grip strength proved to be a more sensitive indicator of development and level of skill than traditionally used parameters of tracking error stabilization and minimization of emotional autonomic shifts. Computation of the ratio of grip strength to tracking error makes it possible to estimate the "physiological cost" and, thus, reliability of operator performance. The device for registering grip strength is incorporated into the control system and may be used in systems providing continuous diagnostic information without interfering with operator performance. PMID- 1898304 TI - Prediction of the exercise-heat tolerance of soldiers wearing protective overgarments. AB - The purpose of this investigation was to see whether subject characteristics and physiologic measurements predicted exercise-heat tolerance (EHT) and voluntary tolerance time in young soldiers. A total of 18 unacclimatized males attempted six 50-min periods of treadmill walking (4.0 km.h-1, 0% grade, 33 degrees C db, 20% rh) while wearing protective overgarments. Two post hoc groups of soldiers were defined: high EHT (H) and low EHT (L), having mean (+/- S.E.) tolerance times of 360 +/- 0 and 222 +/- 12 min, respectively. Significant (p less than 0.05) H vs. L differences were observed in pretrial body mass, percent fat, and mass-to-surface area ratio (M/SA), as well as 170 min HR, Tsk and heat storage. The first three of these factors indicated that preexercise anthropomorphic characteristics may be used to distinguish H from L. The HR and Tsk differences were interpreted to mean that L experienced greater cardiovascular strain in protective overgarments because of a higher Tsk, which resulted in increased pooling of blood in cutaneous vessels, decreased cardiac filling pressure, and increased fatigue. Because HR variables were the strongest correlates of exercise tolerance time (r2 = 0.60 for HR at 170 min, r2 = 0.83 for time to reach HR of 160 beats.min-1) a novel HR monitoring technique was proposed which uses a wrist mounted cardiotachometer to predict tolerance time. PMID- 1898305 TI - Influence of eccentric actions on the metabolic cost of resistance exercise. AB - Maintenance of a low energy expenditure during exercise in space is important because of the confined environment of the space craft. Resistance exercise is receiving increased attention as an exercise countermeasure, and we have shown that training with concentric (con) and eccentric (ecc) muscle actions induces greater increases in strength than training with only con actions. This study determined if performance of both actions markedly increased the metabolic cost of resistance exercise. Seventeen middle-age males performed each repetition of a "warm-up" and four sets of the leg press exercise with only con (Group CON, n = 8) or with con and ecc (Group CON/ECC, n = 9) actions. Sets were separated by 3 min of rest and each was performed to failure by selecting a resistance that allowed performance of the prescribed number of repetitions (7 to 10). The net energy cost of exercise was estimated from oxygen consumption data that were obtained at rest before exercise, during exercise, and for 20 min of recovery. The total work performed during the con actions was about 290 J.kg-1 body weight for both groups. The energy cost for this work was about 3 x 10(-3) cal.J-1. The requirement for the CON/ECC group to also lower the load increased (p less than 0.05) the energy cost 14%. These results indicate that con actions are mainly responsible for the metabolic cost of resistance exercise. Because ecc actions enhance the resistance training-induced increases in strength that are evident with only con actions with minimal additional energy cost, we suggest that they be considered in exercise prescriptions for use in space. PMID- 1898306 TI - Time course and clinical significance of marked left axis deviation in airline pilots. AB - The purpose of this study was to examine the time course and evaluate the clinical significance of marked left axis deviation (LAD) in airline pilots. The study group consisted of 30 Japan Airlines' pilots with marked LAD, identified from a group of 1,700 who are now 35 years of age or older. The mean age at examination was 48.5 +/- 5.7 years [corrected] and the mean observation period was 22.6 +/- 5.6 years [corrected]. The prevalence rate of marked LAD was 1.8%. In 20%, the axis remained unchanged, and in 70%, LAD progressed either gradually or suddenly. All subjects were examined by exercise testing and 26 had echocardiograms. Two pilots (6.7%) were found to have organic heart disease (hypertension), which was much lower than the rate reported previously. In these individuals, the onset of marked LAD was noted more than 10 years before hypertension was detected. No progression to complete left bundle branch block, nor any form of AV block, was observed among these subjects. No cardiac events or death occurred during the study period. PMID- 1898307 TI - The effect of delay on treatment outcome in altitude-induced decompression sickness. AB - Records at the USAF School of Aerospace Medicine, Hyperbaric Medicine Division, were reviewed to determine whether a relationship exists between the length of time from development of symptoms of altitude chamber decompression sickness (DCS) to start of compression therapy and the outcome of treatment. During the 5 year period from 1 January 1984 to 31 December 1988, 233 cases of altitude chamber DCS were treated in USAF hyperbaric chambers. Information obtained from each record included age, sex, time from exposure to symptom onset, time from symptom onset to start of compression therapy, time required for resolution of symptoms, and number of treatment failures (failure to resolve during the first treatment dive or recurrence of symptoms after the first dive). Analysis of the data obtained from treatment records reveals a direct relationship between length of delay to treatment with compression therapy and outcome of treatment. Patients successfully treated with a single treatment dive had an average delay to treatment of 10.6 h. Patients that failed treatment after one dive (failed to resolve or recurred) had an average delay to treatment of 18.2 h. The difference between these groups is significant (p less than 0.05). Outcome of treatment was not significantly related to patient age, sex, or type of symptoms. A discussion of factors causing delays in treatment of decompression sickness is included. PMID- 1898308 TI - Microgravity testing a surgical isolation containment system for space station use. AB - Anticipated hazards for crewmembers in future long term space flights may result in a variety of injuries including trauma and burns. Management of these injuries will require special techniques because of the lack of gravity, limitations of space and environmental restrictions. A small surgical isolation containment system was developed and tested in microgravity. The chamber provided both protection of the injury and of the cabin environment and is felt to be the most effective means of trauma and burn care in future Health Maintenance Facilities planned for prolonged space exposure. PMID- 1898309 TI - Cases from the aerospace medicine residents' teaching file. Case #45. An aviator with a pigmented skin lesion. AB - The initial presentation and diagnosis of an aviator with a pigmented skin lesion. The epidemiology of the skin cancer epidemic, including melanoma is discussed. Prognostic implications of melanoma and the U.S. Air Force experience with melanoma in aircrew are also depicted. PMID- 1898310 TI - Eric Liljencrantz Award--1991. Presented to Frederick E. Guedry, Jr. PMID- 1898311 TI - John A. Tamisiea Award--1991. Presented to Marion C. Wagnon. PMID- 1898312 TI - Julian E. Ward Memorial Award--1991. Presented to Glenn W. Mitchell. PMID- 1898313 TI - Sidney D. Leverett, Jr. Environmental Science Award--1991. Presented to Ian R. Hill. PMID- 1898314 TI - Arnold D. Tuttle Award--1991. Presented to Clare M. Tomaselli. PMID- 1898315 TI - Theodore C. Lyster Award. Presented to Robert R. McMeekin. PMID- 1898316 TI - Raymond F. Longacre Award--1991. Presented to Yuko Nagasawa. PMID- 1898317 TI - Mary T. Klinker Award--1991. Presented to George A. Tirabassi, Jr. PMID- 1898318 TI - Harry G. Moseley Award--1991. Presented to Stanley C. Knapp. PMID- 1898319 TI - Boothby-Edwards Award--1991. Presented to Robert L. Wick, Jr. PMID- 1898320 TI - [The absorption of colostral immunoglobulins in newborn piglets. III. Influence of the duration of colostrum administration]. AB - The gastrointestinal tract of newborn piglets is permeable for intact immunoglobulins ingested with the colostrum. The duration of this passage was investigated by administering hourly rations of 25 ml of either porcine or bovine colostrum for 6, 12, 18 or 24 hrs after birth. The plasma concentrations of the subclasses porcine IgG, IgM and IgA or bovine IgG1, IgG2, IgM and IgA were determined at 12, 18 and 24 hrs after birth and on days 3 and 6. Feeding periods of 6 hrs resulted in plasma Ig levels of the same order of magnitude as observed in natural rearing. These levels were not substantially increased after prolonged feeding. The 6% gain from 6 to 12 feedings seen with porcine colostrum as compared with a gain of 24% for bovine colostrum points at an earlier closure of the intestinal wall for the species-specific proteins. There was no further increase of Ig permeation after 12 hourly feedings. Growth performances and losses were identical in all groups. PMID- 1898322 TI - [Detection of Salmonella-containing food using the 1-2 test]. AB - 133 samples of food were investigated for comparison of a recent commercially available 1-2 test (Biocontrol) with a cultural standard method (non-selective pre-enrichment in buffered peptone water, selective enrichment in Rappaport Vassiliadis-medium and selenite brilliant-green mannitol enrichment broth, inoculation on two selective agars) for presence of Salmonella. The 1-2 test showed in positive results an accuracy ("sensitivity") of 94.7% and in negative results an assurance ("specificity") of 97.9% and is therefore considered suitable for detection of Salmonella contaminated food. PMID- 1898321 TI - [The occurrence of enterotoxigenic Clostridium perfringens strains in the feces of dogs and cats]. AB - A total of 147 faecal specimen of dogs and cats was examined with cultural method for the occurrence of Cl. perfringens and its enterotoxin by using a reversed passive latex agglutination test (Pet-RPLA). Cl. perfringens could be detected in 77.9% of the samples of dogs (n = 68) and 65.6% of cats (n = 32) with diarrhoea in germ counts of 10(4)-10(10) cfu/g faeces. In the group of non diarrhoeic dogs (n = 39) and cats (n = 8) Cl. perfringens was found in 53.9% and 50% of the samples, the germ counts revealed 10(4)-10(8) cfu/g faeces. The enterotoxin of Cl. perfringens was detected in 48.5% of the samples of dogs and 28.1% of cats with diarrhoea. On the other hand this toxin could not be detected in any faecal specimen of non diarrhoeic animals. The in vitro detection of Cl. perfringens enterotoxin was successful at 65% of 20 strains, that had been isolated from faecal samples with enterotoxin. Also 2 Cl. perfringens strains isolated from faeces of non diarrhoeic dogs proved to be enterotoxigenic. The present test results given reason to believe that enterotoxigenic Cl. perfringens strains are involved in the complex of enteric disease of dogs and cats. PMID- 1898323 TI - [Interaction between the central nervous system and the immune system--review]. AB - Results of research within the last years suggest that although the immune system has an autonomous regulation, it is nevertheless subject to control and regulation by the central nervous system. Likewise the central nervous system receives many informations from the immune system. There is a complete regulatory circle between both systems. Disturbances in one system cause changes in the other system. The mechanisms of mutual influences are described and their importance in the pathogenesis of diseases and disturbances of functions are discussed. PMID- 1898324 TI - [The genetic classification of the Pasteurella pneumotropica complex]. AB - Pasteurella pneumotropica with its biotypes Jawetz and Heyl are the most common bacterial pathogens associated with diseases in rodents. 23 P. pneumotropica biotype Jawetz, biotype Heyl and P. pneumotropica-like rodentia isolates have been investigated phenotypically by characterization of their micromorphology and biochemical fermentation reactions. The taxonomic position within the family Pasteurellaceae has been examined by DNA:DNA hybridisation (optical method). It could be shown that P. pneumotropica biotype Jawetz represents a genus-like cluster containing several species including the V-factor dependent Haemophilus Taxon B and the avian P. pneumotropica-like organism and therefore resembles a new species of the new genus. It is concluded that the biotype Heyl of P. pneumotropica taxonomically remains as a species within the family Pasteurellaceae, however without further relationship to other known genera or genus-like groups. PMID- 1898325 TI - Hexose metabolism in pancreatic islets. Glucose-induced and Ca(2+)-dependent activation of FAD-glycerophosphate dehydrogenase. AB - A rise in extracellular D-glucose concentration causes in pancreatic islets a preferential stimulation of aerobic, relative to total, glycolysis. The possible participation in such a phenomenon of a glucose-induced and Ca(2+)-dependent activation of FAD-glycerophosphate dehydrogenase was investigated. In islet homogenates, the activity of the mitochondrial and Ca(2+)-responsive FAD glycerophosphate dehydrogenase was about two orders of magnitude lower than that of the cytosolic and Ca(2+)-insensitive NAD-glycerophosphate dehydrogenase. In islet mitochondria, Ca2+ increased the affinity of the FAD-glycerophosphate dehydrogenase for L-glycerol 3-phosphate, but did not affect the maximal reaction velocity. In the presence of 0.1 mM-L-glycerol 3-phosphate, the Ka for Ca2+ was close to 0.1 microM. When intact islets were preincubated in the presence of both D-glucose and Ca2+, the activity of FAD-glycerophosphate dehydrogenase measured in intact mitochondria incubated in the presence of 1.2 microM-Ca2+ was higher than that recorded under the same conditions in islets preincubated in the absence of D-glucose and/or Ca2+. These findings support the view that, in islets exposed to a high concentration of D-glucose, a Ca(2+)-induced activation of mitochondrial FAD-glycerophosphate dehydrogenase favours the transfer of reducing equivalents by the glycerol phosphate shuttle, and hence accounts, in part at least, for the preferential stimulation of aerobic glycolysis. PMID- 1898326 TI - Quantification of glucose cycling and the extent of equilibration of glucose 6 phosphate with fructose 6-phosphate in islets from ob/ob mice. AB - Pancreatic islets from fed and fasted obese hyperglycaemic (ob/ob) mice were incubated with [1-14C]glucose at 5.5 mM and 16.7 mM, [1-14C]mannose at 16.7 mM, and 3H2O. Yields of 14CO2 and 14C-labelled lactate, and amounts of 14C from [1 14C]mannose incorporated into glucose and of 3H bound to C-2 of glucose, were measured. Glucose utilization was determined from yields of 3H2O from [5 3H]glucose. From the results using 14C, 32-43% of the hexoses phosphorylated to hexose 6-phosphate were estimated to have been dephosphorylated, i.e. cycled. Estimates of hexose cycling from 3H incorporation into glucose were similar. Differences in the ratios of 14C yields in CO2 and lactate indicated incomplete isotopic equilibration between glucose 6-phosphate and fructose 6-phosphate, making the estimates of cycling semi-quantitative. In the fasted state, a larger percentage of the hexose utilized went to lactate than in the fed state. Thus conversion of mannose into glucose in islets indicates the occurrence of glucose cycling in islets. Yields of 14C from [1-14C]mannose, compared with from [1 14C]glucose, provide an approach for quantifying the extent of this cycling. These data provide further evidence for extensive glucose cycling occurring in ob/ob islets in both the fed and the fasted state. PMID- 1898327 TI - Expression in Escherichia coli and characterization of the fatty-acid-binding protein from human muscle. AB - The coding part of the cDNA encoding human muscle fatty-acid-binding protein (FABP) was ligated in the pET8c vector and expressed under the control of the lacUV5 promoter. After induction with isopropyl beta-D-thiogalactopyranoside, almost 12% of the cytoplasmic proteins consisted of FABP. The protein could be isolated after sonication of the bacterial pellet followed by (NH4)2SO4 precipitations, anion-exchange chromatography and gel filtration. The muscle FABP produced in Escherichia coli has an isoelectric point of 5.3 and is recognized by anti-(human muscle FABP) antiserum after Western blotting. The purified FABP has a preference for binding to palmitic acid and C18-C22 (poly)unsaturated fatty acids, and no affinity to palmitoyl-CoA or other hydrophobic ligands tested. The dissociation constant for oleic acid is 0.58 microM, with a binding stoichiometry of 0.72 mol of fatty acid/mol of protein. The physicochemical and binding characteristics of the protein were in complete agreement with those of FABP isolated from human skeletal muscle. PMID- 1898328 TI - Synthesis of a gene for rat liver fatty-acid-binding protein and its expression in Escherichia coli. AB - A gene coding for rat liver fatty-acid-binding protein (FABP) has been constructed by the single-step ligation of ten synthetic oligonucleotides. The gene has been cloned into the bacterial expression vector pKK223-3. Induction of protein synthesis from this gene results in over expression of an FABP that is indistinguishable in its structure and binding properties with that isolated from rat liver. PMID- 1898329 TI - Phorbol-ester-mediated expression of the collagen type I pro-alpha 2 gene in mouse 3T3-L1 cells and its absence in a phorbol 12-myristate 13-acetate-non responsive variant. AB - We have previously isolated a phorbol 12-myristate 13-acetate (PMA)-non responsive variant line (VT-1) from mouse 3T3-L1 cells [Shimizu, Fujiki, Sugimura & Shimizu (1986) Cancer Res. 46, 4027-4031]. Differential hybridization of cDNAs obtained from PMA-treated 3T3-L1 and VT-1 cells resulted in the isolation of a number of unique cDNA clones, including one with a high degree of sequence similarity to the type I pro-alpha 2 collagen gene (COL1A2) [Amagai, Inokuchi, Nishikawa, Shimizu & Shimizu (1989) Somat. Cell Mol. Genet. 15, 153-158]. Here we examined the expression of type I collagen pro-alpha 2 [pro-alpha 2(I)] mRNA and production of type I collagen in these two cell lines. In quiescent cells, the pro-alpha 2(I) steady-state mRNA levels were four times greater in 3T3-L1 cells than in VT-1 cells. PMA addition caused the steady-state levels of pro-alpha 2(I) mRNA to be six times greater in 3T3-L1 cells than in VT-1 cells, with a maximum at 30-60 min. The pro-alpha 2(I) protein levels in the extracellular matrix or culture media of 3T3-L1 cells were substantially elevated by PMA treatment, but no significant increase was detected in VT-1 cells. The correlation of collagen expression with a PMA-mediated mitogenic response suggests a new role for collagen as an early component of mitogenic signal transduction. PMID- 1898330 TI - Inositol 1,3,4,5-tetrakisphosphate-induced Ca2+ sequestration into bovine adrenal medullary secretory vesicles. AB - Ins(1,3,4,5)P4 induced a rapid sequestration of Ca2+ into both secretory vesicles and microsomes of bovine adrenal medulla. The Ca(2+)-sequestering role of Ins(1,3,4,5)P4 contrasts with the Ca(2+)-releasing role of Ins(1,4,5)P3 in adrenal-medullary secretory vesicles and microsomes. The Ins(1,3,4,5)P4-induced Ca2+ sequestration into secretory vesicles was not inhibited by heparin (50 micrograms/ml), whereas Ins(1,4,5)P3-induced Ca2+ release was completely inhibited, indicating two different receptors for Ins(1,4,5)P3 and Ins(1,3,4,5)P4. Furthermore, Ins(1,3,4,5)P4 was as effective at 4 degrees C as at 24 degrees C in sequestering Ca2+ into secretory vesicles, implying Ca2+ sequestration through receptor-operated Ca2+ channels or activation of the Ca(2+) exchange mechanism by Ins(1,3,4,5)P4. The Ca(2+)-sequestering activity of Ins(1,3,4,5)P4 has also been demonstrated with 45Ca2+; 10 microM-Ins(1,3,4,5)P4 induced rapid uptake of 45Ca2+ into secretory vesicles optimized for Ca2+ uptake, whereas 10 microM-Ins(1,4,5)P3 induced 45Ca2+ release from secretory vesicles in similar experiments. PMID- 1898331 TI - Use of D-erythro-sphingosine as a pharmacological inhibitor of protein kinase C in human platelets. AB - Sphingosine is a naturally occurring long-chain amino diol with potent inhibitory activity against protein kinase C in vitro and in cell systems. The use of sphingosine as a pharmacological tool to probe the activity of protein kinase C has been hampered by its amphiphilicity, possible contamination of its commercial preparations, and the existence of other targets for its action. To address these problems, high-purity D-erythro-sphingosine was prepared and employed to develop an approach for the use of sphingosine as a pharmacological agent. The addition of synthetic D-erythro-sphingosine to intact human platelets resulted in quick uptake and preferential partitioning into the particulate fraction. It was rapidly metabolized by intact platelets, 60% being degraded within 1 min after addition. Sphingosine was found to be a potent inhibitor of gamma-thrombin induced aggregation and secretion of washed human platelets. Multiple criteria indicated that this effect is probably mediated through the inhibition of protein kinase C: (1) sphingosine inhibited protein kinase C activity in intact platelets with a similar dose/response to its inhibition of platelet aggregation and secretion; (2) sphingosine inhibited phorbol binding to intact platelets under identical conditions and with a similar dose-dependence; (3) exogenous dioctanoylglycerol overcame sphingosine's inhibition of platelet activation. The effectiveness of sphingosine in inhibiting platelet activation was primarily determined by the ratio of sphingosine to total number of platelets. These data are discussed in relation to a general approach for the use of sphingosine and other parameters for determining biological activities of protein kinase C. PMID- 1898332 TI - Characteristics of Nicotiana tabacum nitrate reductase protein produced in Saccharomyces cerevisiae. AB - Tobacco nitrate reductase (NR) produced in yeast retains cytochrome c reductase activity, but not NR activity. Biochemical data suggest that the haem and FAD domains are functional, and that the molybdenum cofactor (MoCo) domain is inactive owing to the absence of MoCo in yeast. The native form of the produced NR is dimeric. Thus MoCo is not involved in NR dimerization in higher plants, contrary to current assumptions. PMID- 1898333 TI - Dietary fat modifies thromboxane A2-induced stimulation of rat platelets. AB - Diets containing high levels of monounsaturated, n-6 polyunsaturated and n-3 polyunsaturated fatty acids were fed to Wistar rats. This resulted in decreases in the arachidonate content in platelet phospholipids to 91%, 79% and 51% respectively of the level found after feeding a diet rich in saturated fatty acids. In the presence of CaCl2, collagen- and thrombin-induced aggregation of washed platelets from the saturated-fat dietary group (with highest level of arachidonate) was low compared with that of platelets from the other dietary groups, despite a relatively high production of thromboxane B2. On the other hand, n-3 polyunsaturated fatty acids in the diet resulted in platelets aggregating actively, but producing low levels of levels of thromboxane B2. When indomethacin-treated rat platelets were activated with the thromboxane A2 analogue U46619, the presence of a second agonist such as collagen. ADP or thrombin was necessary for aggregate formation. U46619-induced aggregation in combination with either co-activator was relatively low in arachidonate-rich platelets, and was higher in platelets with a low arachidonate content. Similarly, phospholipase C-catalysed formation of L-myo-inositol phosphates was higher in platelets with a low arachidonate content. We conclude that the ability of platelets to react with thromboxane A2 is modified by diet in such a way that a decreased substrate-limited generation of thromboxane A2 is compensated for by an increased response to thromboxane, and vice versa. No significant differences were detected in the binding of U46619 or SQ29548 to platelets from the various dietary groups. Therefore the changed response seems not to be caused by modified properties of the thromboxane A2/prostaglandin H2 receptors, but by altered transduction of the thromboxane signal. PMID- 1898334 TI - Phorbol 12,13-dibutyrate binding to intact human platelets. The role of cytosolic free Ca2+. AB - The role of Ca2+ was examined in regulating the binding of phorbol 12,13 dibutyrate (PdBu) to intact human platelets. Alterations in the cytosolic free Ca2+ concn. [( Ca2+]i), but not extracellular Ca2+, substantially influenced the binding parameters of the phorbol ester. Ca(2+)-depleted platelets demonstrated a significant decline in the maximal binding capacity (Bmax), an increase in equilibrium dissociation constant (Kd) and a decrease in the Hill coefficient (h), suggesting the presence of Ca(2+)-sensitive and Ca(2+)-insensitive populations of PdBu-binding sites. In 1 mM-Ca2+ buffer, thrombin (0.1 NIH unit/ml) and ionomycin (0.5 microM) evoked a rise in [Ca2+]i to approx. 300-500 nM, associated with a significant decline in Kd, but without an apparent effect on Bmax. No effect of thrombin was observed on PdBu binding in Ca(2+)-depleted platelets. Inhibition of protein kinase C (PKC) by H7 was associated with a greater thrombin-evoked [Ca2+]i transient and a decline in Kd. Staurosporine also decreased the Kd for PdBu binding. We propose that this effect of the PKC inhibitors on the Kd was also [Ca2+]i-dependent. These observations in intact platelets indicate that the primary role of agonist- or non-agonist-induced rise in [Ca2+]i is to increase the affinity of PKC for PdBu and, presumably, endogenous diacylglycerol. However, in itself a rise in [Ca2+]i does not increase the Bmax, for PdBu binding. PMID- 1898335 TI - Selective proteolysis of the protein X subunit of the bovine heart pyruvate dehydrogenase complex. Effects on dihydrolipoamide dehydrogenase (E3) affinity and enzymic properties of the complex. AB - Selective proteolysis of the protein X subunit of native bovine heart pyruvate dehydrogenase complex may be accomplished without loss of overall complex activity. Partial loss of function occurs if Mg2+ and thiamin pyrophosphate are not present during proteinase arg C treatment as these cofactors are necessary to prevent cleavage of the E1 alpha subunit. Specific degradation of component X leads to marked alterations in the general enzymic properties of the complex. Lipoamide dehydrogenase (E3) exhibits a decreased affinity for the core assembly and the complex is much more susceptible to inactivation at high ionic strength. The inactive form of the complex is not readily re-activated by removal of salt. It appears that intact protein X and specifically the presence of its cleaved lipoyl domain is not essential for maintenance of an enzymically active pyruvate dehydrogenase complex. However, this protein has an important structural role in promoting the correct association of E3 with the E2 core assembly, an interaction that is required for optimal catalytic efficiency of the complex. PMID- 1898336 TI - Treatment of macrophages with oxidized low-density lipoprotein increases their intracellular glutathione content. AB - Macrophages derived from the human monocyte cell line THP-1 or isolated from the peritoneum of C3H/HEJ mice were incubated with oxidized low-density lipoprotein (LDL) and the total glutathione content (oxidized plus reduced) was measured. An initial depletion of glutathione was followed by an increase, such that after a period of 24 h the glutathione content has approximately doubled. This response required the oxidation of the lipid phase of the LDL molecule, since both native LDL and acetylated LDL had little effect on glutathione levels. The response of the cells to oxidized LDL was dependent on the extent of oxidative modification of the protein. It was also found that 4-hydroxynonenal had a similar effect on THP-1 cells, and we suggest that this or other aldehydes present in oxidized LDL causes the induction of glutathione synthesis in response to an initial oxidative stress and consequent glutathione depletion. In addition, we found that both cell types possess transferases and peroxidases capable of detoxifying aldehydes and peroxides. However, treatment of cells with oxidized LDL or 4-hydroxynonenal for a period of 24 h had no effect on the activities of these enzymes. PMID- 1898337 TI - Mammalian cartilage synthesizes both proteoglycan and non-proteoglycan forms of type IX collagen. AB - Bovine epiphysial cartilage synthesizes both proteoglycan (PG) and non-PG forms of type IX collagen in a ratio of approx. 2:1. The PG form with its attached glycosaminoglycan on the alpha 2(IX) chain is the major form in the medium, whereas both forms are found in the tissue. The results are discussed with regard to cartilage matrix organization. PMID- 1898339 TI - The effect of time of addition of glutamine or nucleosides on proliferation of rat cervical lymph-node T-lymphocytes after stimulation by concanavalin A. AB - 1. Addition of concanavalin A to T-cell lymphocytes from rat cervical lymph nodes increases the activity of glutaminase within 1 h and those of carbamoyl-phosphate synthase II and aspartate transcarbamoylase within 3 h. There was a similar time course for the effects of concanavalin A on rates of glutamine utilization, which was increased within 1 h, and on pyrimidine nucleotide synthesis, which was increased by 40% at 2 h and by 100% at 3 h. 2. A delay in the addition of glutamine to the culture medium after addition of concanavalin A caused a decrease in [3H]thymidine incorporation only after 4-6 h. In the absence of glutamine, delay in addition of guanosine or inosine caused a decrease in [3H]thymidine incorporation only after 6-8 h after the addition of concanavalin A. 3. In contrast, a delay in addition of adenosine or uridine to the culture medium had an immediate effect (i.e. within 2 h) on the rate of incorporation of [3H]thymidine. It is suggested that adenosine and uridine have specific effects on proliferation via specific receptors for these nucleosides in the membrane. PMID- 1898338 TI - Dynamics of platelet-activating-factor release and uptake in a human neutrophil suspension. AB - The present study has examined the dynamics of platelet-activating-factor (PAF) synthesis, release and uptake in order to understand better the trafficking of PAF between cells and medium. Initial experiments indicated that the amount of PAF found on the outside of the cell remained constant well after the synthesis from a precursor had apparently stopped, and in spite of a continued capacity of the cell to take up and catabolize PAF. These results suggested that PAF produced and stored within the cell is eventually released to the outside of the cell at a rate proportional to that of cellular uptake. In order to estimate the amount of PAF released from the cell, the processes of PAF release and uptake were modelled using simple mathematical functions. It was found that, under the experimental conditions used in this study, the uptake of PAF could be expressed as an exponential function tending to a non-zero baseline. Utilizing this rate constant for the uptake of PAF with the amount of PAF outside the cell, the amount of total PAF released from the cell was estimated. Data from the model suggested PAF was released in amounts 10-fold higher than could actually be measured over 30 min. In fact, the model predicted more PAF could be released from the cell than is synthesized, suggesting that a portion of the PAF which is released is taken up and then released again to the outside of the cell. The potential for PAF and/or its intermediates to be recycled was verified by demonstrating that a large proportion of exogenously provided 1-alkyl-2-lyso-sn-glycero-3 phosphocholine is taken up by the neutrophil, converted into PAF and then released again by the cell. These results suggest that PAF trafficking between the cell and medium is complex and involves many processes, which include synthesis, release, uptake, catabolism and recycling. PMID- 1898340 TI - Role of the N-terminal region of phospholipase A2 subunit of beta 1-bungarotoxin in the toxin-Ca2+ complex-formation. AB - beta 1-Bungarotoxin consists of a phospholipase A2 subunit and a non phospholipase A2 subunit. Modification of beta 1-bungarotoxin with CNBr resulted in cleavage at Met-6 and Met-8 of its phospholipase A2 subunit. Analysis of the fluorescence data of both the toxin-Ca2+ complex at 300-350 nm and the toxin-Tb3+ complex at 450-650 nm showed the existence of two binding sites for both metal ions on the different domains of the toxin molecule. At pH 7.6 the association constants for the high-affinity and low-affinity sites of the toxin-Ca2+ complex were determined to be 2.79 x 10(3) +/- 0.21 x 10(3) M-1 and 0.47 x 10(3) +/- 0.06 x 10(3) M-1 respectively. For the toxin-Tb3+ complex the association constant for the high-affinity site was 2.95 x 10(3) +/- 0.43 x 10(3) M-1 and that for the low affinity site was 0.11 x 10(3) +/- 0.03 x 10(3) M-1. Removal of the N-terminal octapeptide of the phospholipase A2 subunit from the toxin molecule caused disintegration of the low-affinity site but did not disrupt the high-affinity site. This might accompany a change in the configuration around His-48 of the phospholipase A2 subunit. Between pH 6 and 8 the binding of metal ions to the high-affinity site increased but that to the low-affinity site did not change with increasing pH. The neurotoxicity and enzymic activity of the toxin were lost on removal of the low-affinity site. PMID- 1898341 TI - Identification of a second neutrophil-chemoattractant cytokine generated during an inflammatory reaction in the rabbit peritoneal cavity in vivo. Purification, partial amino acid sequence and structural relationship to melanoma-growth stimulatory activity. AB - The intraperitoneal injection of zymosan in the rabbit results in the generation of an inflammatory exudate containing oedema-forming and chemoattractant activities. Previous studies demonstrated the early appearance of the complement fragment C5a, followed by the generation of two mediators related to the cytokine interleukin-8 that were separable by cation-exchange h.p.l.c. N-Terminal amino acid sequencing identified one of these mediators as rabbit interleukin-8. This paper describes the purification of the second cytokine by cation-exchange, gel filtration and reversed-phase h.p.l.c. The purified material had both oedema forming and chemoattractant activity when assayed in rabbit skin in vivo. On SDS/PAGE a single 6-8 kDa band was observed and N-terminal amino acid sequencing of the reduced and alkylated protein positively identified 36 amino acids. This sequence revealed the rabbit homologue of melanoma-growth-stimulatory activity. The identification of these two cytokines in vivo will provide an opportunity to investigate the importance of their co-release in the inflammatory process. PMID- 1898342 TI - Evidence that the androgen receptor mediates sexual differentiation of mouse renal cytochrome P450 expression. AB - We have previously shown that sexual dimorphism in the expression of mouse renal cytochrome P450s is mediated by androgens, probably at a transcriptional level [Henderson, Scott, Yang & Wolf (1990), Biochem. J. 266, 675-681]. In the present study we show that this effect is already observed for most isoenzymes at only 2 3 weeks of age, as is the ability to induce or suppress expression with exogenous testosterone. The testosterone responsiveness did, however, exhibit age- as well as dose-dependency. Intriguingly, the effects of androgen took up to 8 days to become maximized, and the dose of testosterone needed to convert the female into the male phenotype was much higher than the circulating levels normally found in males. Studies using testicular feminized (Tfm) male mice, which carry an androgen receptor defect, showed them to have the female kidney cytochrome P450 phenotype, and these animals were not responsive to testosterone treatment. These data demonstrate the involvement of the androgen receptor in the regulation process. Taken together, our results indicate that the androgen receptor does not interact directly with the P450 genes, but initiates a cascade of events leading to the changes in cytochrome P450 gene expression. Significant differences were observed in the degree of sexual dimorphism in kidney P450 expression in other mammalian species. The significance of these findings in relation to the observed sexual dimorphism in other species is discussed. PMID- 1898343 TI - Carbohydrate structure of human pancreatic elastase 1. AB - Human pancreatic elastase 1 (E1) is a glycoprotein containing two potential N glycosylation sites, one of which carries a carbohydrate moiety [Wendorf, Geyer, Sziegoleit & Linder (1989) FEBS Lett. 249, 275-278]. In order to study its glycosylation, glycoprotein isolated from post-mortem pancreas tissue of 75 donors was digested with trypsin. Oligosaccharides were liberated from resulting glycopeptides by treatment with peptide-N4-(N-acetyl-beta-glycosaminyl) asparagine amidase F, radiolabelled by reduction with KB3H4 and separated by h.p.l.c. and gel filtration. Major oligosaccharide alditol fractions, representing 67.8 mol% of total glycans, were characterized by methylation analysis and sequential degradation with exoglycosidases. The results revealed that about two-fifths of the partially truncated, mainly biantennary, complex type glycans found comprised blood group A, B, Lea (or X), difucosyl A or difucosyl B determinants, which could be assigned to lactosamine antennae linked to Man(alpha 1-3)- residues of the sugar chains. PMID- 1898344 TI - Up-regulation of glucose metabolism in Kupffer cells following infusion of tumour necrosis factor. AB - Alterations of glucose metabolism and the oxidation of glutamine and palmitate were studied, by using specifically labelled substrates, in freshly isolated Kupffer cells and hepatic endothelial cells after infusion in vivo of human recombinant tumour necrosis factor-alpha (TNF; 7.5 x 10(5) IU/30 min per kg body wt., intravenously). Cells were incubated in a medium containing 5 mM-glucose, 0.4 mM-palmitate, 1 mM-lactate and 0.5 mM-glutamine. Administration of TNF in vivo increased glucose use in Kupffer cells by 70%. Glucose oxidation in the tricarboxylic acid cycle and flux in the Embden-Meyerhof (EM) pathway were elevated by 40 and 80% respectively. Treatment in vitro with 1 microM-phorbol 12 myristate 13-acetate (PMA) resulted in a similar percentage increase in glucose use by Kupffer cells prepared from either saline- or TNF-treated rats. However, PMA increased the activity of the hexose monophosphate shunt (HMS) by 3- and 10 fold in cells isolated from saline- or TNF-infused animals respectively. A phagocyte stimulus in vitro, opsonized zymosan, increased glucose use by 30% and doubled the flux through the HMS in Kupffer cells from saline-infused animals. The activity of the HMS in response to zymosan was increased by 400% after TNF treatment. In endothelial cells, basal glucose utilization was not altered by TNF treatment. PMA increased HMS activity in endothelial cells to a similar degree after saline or TNF infusion. Zymosan, however, increased HMS activity only in endothelial cells from TNF-treated rats. Oxidation of palmitate or glutamine was not affected by TNF treatment either under basal conditions or after challenge in vitro. Our data indicate that, after phagocytosis in vitro or protein kinase C activation, glucose use and flux through the HMS increase in Kupffer cells. This is accompanied by increased glycolytic flux, with no changes in glucose oxidation in the tricarboxylic acid cycle. After TNF exposure, followed by a secondary stimulus, the enhanced glucose use by Kupffer cells is primarily channelled through the HMS pathway. These data suggest that the increased glucose use in vivo by Kupffer cells found after immune-stimulated conditions may subserve primarily the increased need for NADPH and HMS intermediates. PMID- 1898345 TI - Enhanced choline and Rb+ transport in human erythrocytes infected with the malaria parasite Plasmodium falciparum. AB - Human erythrocytes infected in vitro with the malaria parasite Plasmodium falciparum showed a markedly increased rate of choline influx compared with normal cells. Choline transport into uninfected cells (cultured in parallel with infected cells) obeyed Michaelis-Menten kinetics (Km approximately 11 microM). In malaria-parasite-infected cells there was an additional choline-transport component which failed to saturate at extracellular concentrations of up to 500 microM. This component was less sensitive than the endogenous transporter to inhibition by the Cinchona bark alkaloids quinine, quinidine, cinchonine and cinchonidine, but showed a much greater sensitivity than the native system to inhibition by piperine. The sensitivity of the induced choline transport to these reagents was similar to that of the malaria-induced (ouabain- and bumetanide resistant) Rb(+)-transport pathway; however, the relative magnitudes of the piperine-sensitive choline and Rb+ fluxes in malaria-parasite-infected cells varied between cultures. This suggests either that the enhanced transport of the two cations was via functionally distinct (albeit pharmacologically similar) pathways, or that the transport was mediated by a pathway with variable substrate selectivity. PMID- 1898346 TI - Evaluation of 5- and 6-fluoro derivatives of arachidonic acid and 5,8,14 eicosatrienoic acid as substrates and inhibitors of 5-lipoxygenase. AB - The 5- and 6-fluoro derivatives of arachidonic acid (5F-ETE and 6F-ETE) were evaluated as substrates of rat basophilic leukaemia cell (RBL-1) 5-lipoxygenase. 5F-ETE was found to be a poor substrate and was converted into a single product, 5-oxoeicosa-6,8,11,14-tetraenoic acid (5-oxo-ETE). 6F-ETE was a good substrate and was mainly converted into 5-hydroperoxy-6-fluoroeicosa-6,8,11,14-tetraenoic acid (5-OOH-6F-ETE) with concomitant formation of a small amount of 5-oxo-6 fluoroeicosa-6,8,11,14-tetraenoic acid (5-oxo-6F-ETE). However the formation of 5,12-dihydroxy-6-fluoroeicosa-6,8,10,14-tetraenoic acids, epimeric at C-12, was not observed. Eicosa-5(Z),8(Z),14(Z)-trienoic acid (ET), previously described as a good substrate of 5-lipoxygenase, is oxidized mainly to 5-hydroperoxyeicosa 6,8,14-trienoic acid (5-OOH-ET), which does not serve as a substrate for the leukotriene A4 (LTA4) synthase activity of 5-lipoxygenase [Nave, Dulery, Gaget & Ducep (1988) Prostaglandins 36, 385-398]. To allow a better estimation of the effect of fluorine substitution on the rate of oxidation of the 5,8-cis,cis-diene moiety by 5-lipoxygenase, the 5- and 6-fluoro derivatives of ET were studied as substrates. Qualitatively, the metabolism of 5F-ET and 6F-ET was found to be similar to that observed for 5F-ETE and 6F-ETE. Quantitatively, 6F-ET proved to be a somewhat better substrate than ET, whereas 5F-ET was poorly metabolized. The relative ability of arachidonic acid, ET and the corresponding 5- and 6-fluoro derivatives to inhibit the 5-lipoxygenase-catalysed oxidation of eicosa-5(Z),8(Z) dienoic acid (ED) was also investigated. 6F-ETE and 5F-ETE were found to be effective and about equipotent inhibitors of 5-lipoxygenase in the micromolar range. In view of their close structural similarity to arachidonic acid, these two inhibitors are expected to be important tools in the study of the 5 lipoxygenase pathway in vivo. PMID- 1898348 TI - Human renin in transgenic mouse kidney is localized to juxtaglomerular cells. AB - To examine whether expression of human renin in the transgenic mouse kidney is regulated in a cell-specific manner, we have characterized monoclonal antibodies against human renin and determined the renin-production site by immunohistochemistry. By using a monoclonal antibody specific for human renin, A6 11-6, we demonstrated that human renin in the transgenic mouse kidney is localized to the juxtaglomerular cells of afferent arterioles. PMID- 1898347 TI - Studies on the biotin-binding site of avidin. Minimized fragments that bind biotin. AB - The object of this study was to define minimized biotin-binding fragments, or 'prorecognition sites', of either the egg-white glycoprotein avidin or its bacterial analogue streptavidin. Because of the extreme stability to enzymic hydrolysis, fragments of avidin were prepared by chemical means and examined for their individual biotin-binding capacity. Treatment of avidin with hydroxylamine was shown to result in new cleavage sites in addition to the known Asn-Gly cleavage site (position 88-89 in avidin). Notably, the Asn-Glu and Asp-Lys peptide bonds (positions 42-43 and 57-58 respectively) were readily cleaved; in addition, lesser levels of hydrolysis of the Gln-Pro (61-62) and Asn-Asp (12-13 and 104-105) bonds could be detected. The smallest biotin-binding peptide fragment, derived from hydroxylamine cleavage of either native or non glycosylated avidin, was identified to comprise residues 1-42. CNBr cleavage resulted in a 78-amino acid-residue fragment (residues 19-96) that still retained activity. The data ascribe an important biotin-binding function to the overlapping region (residues 19-42) of avidin, which bears the single tyrosine moiety. This contention was corroborated by synthesizing a tridecapeptide corresponding to residues 26-38 of avidin; this peptide was shown to recognize biotin. Streptavidin was not susceptible to either enzymic or chemical cleavage methods used in this work. The approach taken in this study enabled the experimental distinction between the chemical and structural elements of the binding site. The capacity to assign biotin-binding activity to the tyrosine containing domain of avidin underscores its primary chemical contribution to the binding of biotin by avidin. PMID- 1898349 TI - Expression of the rabbit intestinal N2 Na+/nucleoside transporter in Xenopus laevis oocytes. AB - Polyadenylated [poly(A)+] mRNA isolated from rabbit small-intestinal mucosa was injected into Xenopus laevis oocytes, and expression of the N2 Na+/nucleoside co transporter was assayed by measuring Na(+)-dependent thymidine uptake. Expression of Na(+)-dependent thymidine uptake steadily increased after mRNA injection and was on average increased 11-fold by day 6 over background. Na(+)-dependent thymidine uptake was saturable (apparent Km approximately 30 microM at 22 degrees C) and inhibited by uridine and cytidine, but not by guanosine and inosine. These properties of the expressed thymidine transport strongly suggest that the epithelial N2 Na+/nucleoside co-transporter can be expressed in X. laevis oocytes. PMID- 1898351 TI - Differential rates of conversion of rat proinsulins I and II. Evidence for slow cleavage at the B-chain/C-peptide junction of proinsulin II. AB - Rat proinsulin I is converted into insulin more rapidly than is proinsulin II. To study this further, rat islets were labelled (10 min) and conversion kinetics of the labelled proinsulins were monitored during a 120 min chase. Proinsulins, conversion intermediates and both insulins were separated by h.p.l.c. The accumulation of des-64,65-(split proinsulin II) during the chase suggests that the B-chain/C-peptide junction of proinsulin II is cleaved more slowly than the equivalent site on proinsulin I. This accounts for the differential kinetics of conversion of proinsulins I and II, and is presumed to be caused by one (or more) of the amino acid replacements which distinguish the two proinsulins. PMID- 1898352 TI - Human salivary cystatin S. Cloning, sequence analysis, hybridization in situ and immunocytochemistry. AB - A human submandibular-gland (SMG) cDNA library was constructed in a lambda was constructed in a lambda gt11 Sfi-Not orientation-specific expression vector and then screened with antibody generated against human salivary cystatins. The clone C4-4 encoded an N-terminally truncated cystatin S, whereas the others encoded cystatin SN. The library was then rescreened with the C4-4, and the inserts of several positive clones were directly amplified from the eluted plaques by linear PCR and the PCR products analysed by Southern blotting and direct DNA sequencing. Two clones (C3 and C12) encoded a full-length secreted cystatin S and its leader peptide and included 5'- and 3'-untranslated regions. These clones showed a high degree of sequence similarity to cDNA clones encoding human salivary cystatin SN and genomic clones encoding cystatin SN and SA. Hybridization in situ of normal human SMG and parotid-gland (PG) tissue sections localized the cystatin-gene transcripts to the cytoplasm of serous acinar cells of both glands, with a much higher concentration of cystatin mRNA in the SMG. Immunocytochemistry localized the salivary cystatin gene products also to the serous cells, and the levels of cystatin protein correlated with the amount of cystatin mRNA, with a much stronger signal in the SMG than in the PG. PMID- 1898353 TI - The role of caffeine-sensitive Ca2+ stores in agonist- and inositol 1,4,5 trisphosphate-induced Ca2+ release from bovine adrenal chromaffin cells. AB - In single bovine adrenal chromaffin cells loaded with fura-2, histamine, angiotensin II (AII) and caffeine elicited large transient increases of intracellular free Ca2+ concentration [( Ca2+]i) in the absence of external Ca2+, with peak amplitudes averaging 726 +/- 138 (n = 14), 710 +/- 102 (n = 21) and 830 +/- 100 nM (n = 30) respectively. A substantial portion of the agonist-induced rise in [Ca2+]i depended on Ca2+ release from caffeine-sensitive stores, as pretreatment with caffeine diminished subsequent agonist responses by 90-95%. Conversely, pretreatment with histamine or AII decreased subsequent caffeine responses by 100% and 90% respectively. The effects of caffeine most likely resulted from activation of a Ca(2+)-induced Ca(2+)-release (CICR) process, whereas histamine and AII initially acted through generation of Ins(1,4,5)P3. The relationship of Ins(1,4,5)P3- and caffeine-sensitive Ca2+ pools was studied by using alpha-toxin-permeabilized chromaffin cells. Evidence was found for three non-mitochondrial, ATP-dependent, Ca2+ pools: one exclusively sensitive to Ins(1,4,5)P3 (pool 1), a second sensitive to both Ins(1,4,5)P3 and caffeine (pool 2), and a third exclusively sensitive to caffeine (pool 3). The existence of pools 1 and 3, and the ability of agonists such as histamine to discharge pool 3 completely, supports a two-pool model in which a caffeine-sensitive CICR mechanism plays a major role in the generation of agonist-induced Ca2+ spikes in bovine chromaffin cells. PMID- 1898350 TI - Regulation of gene expression by insulin. PMID- 1898354 TI - Alterations in the metabolism of very-low- and low-density lipoproteins after partial ileal-bypass surgery in the Watanabe heritable hyperlipidaemic rabbit. AB - The influence of interruption of bile-acid enterohepatic circulation by partial ileal bypass (PIB) surgery on serum lipids, lipoproteins and the turnover of very low- (VLDL) and low-density (LDL) lipoproteins was investigated in Watanabe heritable hyperlipidaemic (WHHL) rabbits. Compared with controls, total serum cholesterol was 48% lower after PIB (16.88 +/- 1.57 versus 8.79 +/- 1.66 mmol/l; P less than 0.01), owing to lower levels of cholesterol in VLDL (-23%), intermediate-density lipoprotein (IDL; -39%) and LDL (-72%); serum triacylglycerols were 32% higher (3.86 +/- 1.35 versus 5.11 +/- 0.82 mmol/l). The ratio of the percentages of mass of cholesteryl esters to triacylglycerols was 71% lower in VLDL and LDL and 67% lower in IDL (P less than 0.01). Compared with controls, the secretion rate of LDL was 33% lower (31.1 +/- 7.2 versus 20.7 +/- 6.9 mg/day per kg; P less than 0.05) and the fractional catabolic rate (FCR) of LDL was 33% higher (0.46 +/- 0.06 versus 0.61 +/- 0.12 pool/day; P less than 0.02). The VLDL turnover showed that after PIB there was a higher secretion rate of VLDL apolipoprotein B (63.9 versus 167.4 mg/day per kg), a higher FCR (3.84 versus 8.61 pools/day), a higher direct uptake (38.8 versus 146.4 mg/day per kg) and a higher conversion of VLDL into LDL (4.8 versus 9.0 mg/day per kg). Some 82% of LDL originated from direct synthesis in controls, and after PIB this was 59%. In both controls and treated rabbits there was a direct LDL synthesis, which was 52% lower after PIB (26.3 versus 12.6 mg/day per kg). It is concluded that LDL cholesterol lowering by PIB is due to an increased uptake of LDL, a decreased synthesis of LDL, and cholesterol depletion of the LDL particles; the decreased LDL synthesis is due to a decreased direct production of LDL, which exceeds the increased conversion of VLDL into LDL. PMID- 1898355 TI - The importance of alcohol dehydrogenase in regulation of ethanol metabolism in rat liver cells. AB - We used titration with the inhibitors tetramethylene sulphoxide and isobutyramide to assess quantitatively the importance of alcohol dehydrogenase in regulation of ethanol oxidation in rat hepatocytes. In hepatocytes isolated from starved rats the apparent Flux Control Coefficient (calculated assuming a single-substrate irreversible reaction with non-competitive inhibition) of alcohol dehydrogenase is 0.3-0.5. Adjustment of this coefficient to allow for alcohol dehydrogenase being a two-substrate reversible enzyme increases the value by 1.3-1.4-fold. The final value of the Flux Control Coefficient of 0.5-0.7 indicates that alcohol dehydrogenase is a major rate-determining enzyme, but that other factors also have a regulatory role. In hepatocytes from fed rats the Flux Control Coefficient for alcohol dehydrogenase decreases with increasing acetaldehyde concentration. This suggests that, as acetaldehyde concentrations rise, control of the pathway shifts from alcohol dehydrogenase to other enzymes, particularly aldehyde dehydrogenase. There is not a single rate-determining step for the ethanol metabolism pathway and control is shared among several steps. PMID- 1898357 TI - Determination of the pKa of glucuronic acid and the carboxy groups of heparin by 13C-nuclear-magnetic-resonance spectroscopy. AB - As part of our continuing studies on heparin, the present paper uses 13C-n.m.r. spectroscopy to examine the acidity of heparin's uronic acid carboxylate groups. Heparin contains three different uronic acids. In porcine mucosal heparin these account for approx. 91, 7 and 2 mol% of the total uronic acid residues. These are alpha-L-idopyranosyluronic acid 2-sulphate, beta-D-glucopyranosyluronic acid and alpha-L-idopyranosyluronic acid. The pKa values of their carboxylate groups were determined as 3.13 (using heparin), 2.79 (using heparin) and 3.0 (predicted by using model compounds) respectively. 18C-n.m.r. spectroscopy, performed at various pH values, provided a convenient method of simultaneously determining the pKa of multiple carboxylate groups, of similar acidity, within heparin D Glucopyranosyluronic acid and heparin-derived di-, tetra- and hexa-saccharides were used as model compounds to determine pKa values of the different carboxy groups. The results suggested that molecular size had an effect on pKa. Unambiguous assignment of carboxy carbon resonances were accomplished through the use of two-dimensional n.m.r. spectroscopy. Finally, application of this method to the simplest model compound, D-glucopyranosyluronic acid, permitted the determination of the pKa of both its alpha- and beta-anomers. PMID- 1898356 TI - Regulation of epidermal-growth-factor-receptor signal transduction by cis unsaturated fatty acids. Evidence for a protein kinase C-independent mechanism. AB - The effect of acute treatment with non-esterified fatty acids (NEFA) on transmembrane signalling has been investigated in three different cell lines. In EGFR T17 cells, pretreatment with cis-unsaturated (oleic and palmitoleic acids) NEFA, but not with saturated or trans-unsaturated NEFA, inhibited the epidermal growth-factor (EGF)-induced increases in cytosolic [Ca2+], membrane potential and Ins(1,4,5)P3 generation. The blocking effect was found to be time- and dose dependent and rapidly reversible after washout. However, oleic acid treatment did not block either binding of 125I-EGF to its receptor or EGF-induced autophosphorylation of the EGF receptor. The mechanism of action of NEFA could not be attributed to protein kinase C activation, since (i) down-regulation of the enzyme by long-term treatment with phorbol esters did not prevent blockade by oleic acid, and (ii) the effects of acutely administered phorbol ester and oleic acid were additive. In this cell line, signalling at bradykinin and bombesin receptors was also impaired by oleic acid. In A431 cells, oleic acid also blocked signal transduction at the EGF and B2 bradykinin receptors. Finally, in PC12 cells, oleic acid blocked the Ca2+ influx mediated by the activation of B2 bradykinin receptors. IN CONCLUSION: (1) NEFA block signal transduction by interfering with receptor-phospholipase C or phospholipase C-substrate interaction without preventing ligand binding; (2) NEFA do not act by a protein kinase C-mediated mechanism; (3) the effect of NEFA is dependent on their configuration rather than hydrophobicity or chain length; (4) this effect is evident in several different cell lines and receptor systems. PMID- 1898358 TI - Spiking of intracellular calcium ion concentration in single cultured pig aortic endothelial cells stimulated with ATP or bradykinin. AB - Single pig aortic endothelial cells in culture loaded with the Ca(2+)-sensitive fluorescent dye Indo-1 were stimulated with ATP (0.1-100 microM) or bradykinin (0.1-5.0 nM). Spiking or oscillations of [Ca2+]i were seen in approx. 50% of cells stimulated with either agonist. Non-spiking or transient responses in which [Ca2+]i returned to pre-stimulation levels rapidly 9120-250 s), or sustained responses in which [Ca2+]i remained elevated for many minutes, were seen in a further 20% of cells in each case, stimulated with either agonist. There was a marked variation between individual cells in the latency, magnitude, frequency and overall pattern of oscillations induced by ATP and bradykinin, although the patterns of response to bradykinin were less variable. In cells where repetitive spikes were seen, a relation between concentration of ATP and the latency of the response and the frequency of spiking was evident. Effects of removal of extracellular Ca2+, elevation of extracellular K+ concentration (35 or 70 mM) or exposure to phorbol 12,13-dibutyrate or 1,2-dioctanoyl-sn-glycerol were tested on the spiking Ca2+ responses. Each of these procedures reversibly slowed or prevented Ca2+ spiking evoked by ATP or bradykinin. In contrast, the inactive phorbol ester 4 alpha-phorbol didecanoate had no effect on Ca2+ spiking evoked by these hormones. Our results thus indicate that the responses of single cells to ATP or bradykinin exhibit marked heterogeneity, and suggest that secretory events driven by extracellular Ca2+ may be regulated by repetitive spikes or oscillations of Ca2+. PMID- 1898359 TI - Quantal Ca2+ mobilization stimulated by inositol 1,4,5-trisphosphate in permeabilized hepatocytes. AB - In several cell types, including hepatocytes, submaximal concentrations of Ins(1,4,5)P3 stimulate an initial rapid mobilization of intracellular Ca2+ stores that is followed by either no further Ca2+ release or very much slower release. Further additions of Ins(1,4,5)P3 then evoke further Ca2+ mobilization. Such 'incremental' responses [Meyer & Stryer (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 3841-3845] could result from all-or-nothing emptying of stores that differ in their sensitivities to Ins(1,4,5)P3 or from partial emptying of stores that are more uniformly sensitive, but unable to release all of their Ca2+ because the response to Ins(1,4,5)P3 rapidly attenuates. By measuring unidirectional 45Ca2+ efflux from intracellular stores stimulated with Ins(1,4,5)P3 under conditions where they continue to sequester 40Ca2+, we provide evidence suggesting that Ins(1,4,5)P3 stimulates all-or-nothing emptying of stores that differ in their sensitivities to Ins(1,4,5)P3, a quantal response pattern. PMID- 1898360 TI - Substrate and pH effects on glutamine synthesis in rat liver. Consequences for acid-base regulation. AB - Switching in acidosis of hepatic nitrogen disposal from urea synthesis to NH4+ and net glutamine production was demonstrated in the isolated perfused livers of starved male Wistar rats. Lactate was preferred to glucose as the substrate for the carbon skeleton of glutamine synthesized over the pH range 6.9-7.5. This is necessary if the switch away from a proton-producing process (ureagenesis) in acidosis is to constitute an acid-base regulating system intrinsic to the liver. Glutamine balance shifted with pH from marked net uptake to small net output under acidotic conditions (pH 7.5-6.9), an effect due solely to a decrease in glutamine uptake. NH4+ uptake by the liver had a linear relationship with pH, being markedly decreased in acidosis because glutamine synthesis was insufficient to compensate for the decreased incorporation into urea. Animals rendered chronically acidotic showed a lower central venous plasma urea concentration and a raised NH4+ concentration, but their livers synthesized no more glutamine when perfused at an acidotic pH than did normal livers. We conclude that perivenous hepatocytes may not be efficient scavengers of NH4+ ions, which must be partly disposed of elsewhere by non-proton-generating pathways if inhibition of ureagenesis is to represent a hepatic acid-base regulating system. PMID- 1898361 TI - Glucosidase II from rat liver microsomes. Kinetic model for binding and hydrolysis. AB - Glucosidase II is an enzyme involved in glycoprotein biosynthesis, releasing both alpha-1,3-linked glucose residues from the protein-linked oligosaccharide Glc2Man9GlcNAc2-R in the processing of N-glycans. We studied the kinetic properties of the enzyme, purified to homogeneity and, for the first time, we have been able to demonstrate the occurrence of two active sites in this enzyme and to establish the mechanisms of binding and hydrolysis of the physiological substrate at its active site(s). The analyses of data fitting to single and double hyperbolic equations and the Eadie-Hofstee profile, together with the inhibition kinetics, demonstrate that the enzyme has two different active sites. The Km and Vmax. values for the high-affinity site (site 1) were 0.78 mM and 437 munits/mg respectively, whereas the values for the low-affinity site (site 2) were 481 mM and 13797 munits/mg respectively, for the p-nitrophenyl alpha-D glucopyranoside substrate. The Vmax./Km ratios, which indicate the efficacy of an active site for a substrate, were 560 and 28.7 ml/min per g for active sites 1 and 2, respectively. The inhibition type, with respect to site 1, for glucose, maltose, D-glucone-delta-lactone, CaCl2 and MgCl2 was pure-competitive, partial competitive, parabolic, non-competitive and non-competitive respectively. Ki values for glucose, maltose, CaCl2 and MgCl2 were 6.75, 2.05, 10.60 and 14.20 mM respectively. Thus glucose would bind to active site 1, maltose to site 2 (and near to site 1) and D-glucone-delta-lactone to either site 1 or 2. The following hydrolysis mechanism for the physiological substrate (Glc2Man9GlcNAc2-protein) of glucosidase II may be concluded from all the foregoing kinetic evidence: the external glucose would be the first released residue, at active site 2, thereafter producing Glc1Man9GlcNAc2-protein; the remaining glucose would be released at active site 1, delivering the Man9GlcNAc2-protein product, which would leave the enzyme. PMID- 1898362 TI - Immobilization of polynucleotides on magnetic particles. Factors influencing hybridization efficiency. AB - Immobilization of oligonucleotides containing 5'-terminal thiol groups on thiol terminated paramagnetic Biomag beads via disulphide bond formation was investigated. Oligonucleotides are demonstrated to couple at high yields, the linkage is stable at 90 degrees C and is reversible, and the immobilized oligonucleotide is available for complementary, but not non-complementary, hybridization. Specific hybridization capacity per micrograms of immobilized oligonucleotide exceeds that achieved with other forms of immobilization chemistries employing random attachment and/or specific end attachment of the oligonucleotide to the solid support. Adsorption of DNA on the surface of the beads was decreased by incubation in 0.2% SDS; other non-specific blocking agents had no effect. Brief heating of the beads possessing immobilized oligonucleotides at 90 degrees C before hybridization increased the amount of specific hybridization dependent upon the inclusion of poly(dT) spacer sequences 5' to the immobilized oligonucleotide and 3' to the thiol group. Increasing lengths of spacers [up to a poly(dT16) spacer] linearly increased hybridization of complementary sequences. PMID- 1898363 TI - Isolation of H-protein loaded with methylamine as a transient species in glycine decarboxylase reactions. AB - A three-step protocol was devised to purify H-protein, which can be readily released as a soluble protein from pea mitochondria. After the final step of purification (anion-exchange chromatography) the native enzyme was eluted as two distinct peaks at 250 and 350 mM-KCl if the lysis buffer contained glycine. Each from exhibited an identical Mr of 15000 on SDS/PAGE and they were not distinguishable by PAGE under non-denaturating conditions. Both forms catalysed the rapid fixation of [14C]bicarbonate to the carboxy group atom of glycine during the exchange reaction, whereas the reversible exchange of electrons between NADH and lipoamide bound to the H-protein in the presence of 5,5' dithiobis-(2-nitrobenzoic acid) was seen only with the form eluted at 350 mM-KCl. During the early steps of H-protein isolation, when P- and H-protein react together in the presence of glycine, the methylamine intermediate bound to the lipoamide of the H-protein accumulates in the medium at the expense of oxidized H protein. Under these conditions the methylamine intermediate, which is a rather stable structure, was easily separated from the oxidized H-protein on ion exchange chromatography. The methylamine bound to the lipoamide of the H-protein prevented the reversible exchange of electrons between NADH and lipoamide. High concentrations of glycine were required for the loading of H-protein with methylamine catalysed by a large excess of P-protein. PMID- 1898364 TI - Regulation of liver cell volume and proteolysis by glucagon and insulin. AB - The effects of insulin and glucagon on liver cell volume and proteolysis were studied in isolated perfused rat liver. The rate of proteolysis was assessed as [3H]leucine release from single-pass-perfused livers from rats which had been prelabelled in vivo by intraperitoneal injection of [3H]leucine. The intracellular water space was determined from the wash-out profiles of simultaneously added [3H]inulin and [14C]urea. In normo-osmotic (305 mosM) control perfusions the intracellular water space was 548 +/- 10 microliters/g wet mass (n = 44) and was increased by 16.5 +/- 2.6% (n = 6), i.e. by 85 +/- 14 microliters/g, after hypoosmotic exposure (225 mosM). Glucagon (0.1 microM) decreased the intracellular water space by 17 +/- 4% (n = 4), whereas insulin (35 nM) increased the intracellular water space by 9.3 +/- 1.4% (n = 15). Also, in isolated rat hepatocyte suspensions insulin (100 nM) caused cell swelling by 10.7 +/- 1.8% (n = 16), which was fully reversed by glucagon. In perfused liver, insulin-induced cell swelling was accompanied by a hepatic net K+ uptake (4.5 +/- 0.2 mumol/g) and an inhibition of proteolysis by 21 +/- 2% (n = 12); further addition of glucagon led to a net K+ release of 3.8 +/- 0.2 mumol/g (n = 7) and fully reversed the insulin effects on both cell volume and proteolysis. Similarly, insulin-induced cell swelling and inhibition of proteolysis were completely antagonized by hyperosmotic (385 mosM) cell shrinkage. Furthermore, cell swelling and inhibition of proteolysis after hypo-osmotic exposure or amino acid addition were reversed by glucagon-induced cell shrinkage. There was a close relationship between the extent of cell swelling and the inhibition of proteolysis, regardless of whether cell volume was modified by insulin, glucagon or aniso-osmotic exposure. The data show that glucagon and insulin are potent modulators of liver cell volume, at least in part by alterations of cellular K+ balance, and that their opposing effects on hepatic proteolysis can largely be explained by opposing effects on cell volume. It is hypothesized that hormone induced alterations of cell volume may represent an important, not yet recognized, mechanism mediating hormonal effects on metabolism. PMID- 1898365 TI - Characterization of a novel glutathione S-transferase isoenzyme from mouse lung and liver having structural similarity to rat glutathione S-transferase 8-8. AB - In mouse lung, glutathione S-transferase (GST, EC 2.5.1.18) isoenzymes belonging to the three major known classes, Alpha, Mu and Pi, have been previously characterized, along with an isoenzyme (pI 5.7) that could not be identified with the Alpha, Mu or Pi classes of GSTs. In the present studies we have demonstrated that this isoenzyme is also expressed in liver. Its structural, kinetic, and immunological properties have been determined and compared with those of the three classes of GSTs. GST 5.7 has a subunit molecular mass of 23 kDa, which is intermediate between that of the previously characterized Alpha (25 kDa) and Pi (22.5 kDa) class GST subunits of mouse lung. Comparison of peptide maps of GST 5.7 with those representative of Alpha, Mu and Pi class GST isoenzymes of mouse lung showed that it had a distinct peptide fragmentation pattern. Kinetic and immunological properties of GST 5.7 were also distinct from other mouse GST isoenzymes belonging to the Alpha, Mu or Pi classes. N-Terminal amino-acid sequence analysis of a 6 kDa fragment generated by CNBr digestion of mouse lung GST 5.7 revealed a 15-residue sequence that was distinct from sequences of known Alpha, Mu and Pi class mouse GSTs. The sequence, however, matched with the sequence of rat GST 8-8 between amino acid residues 106 and 120 with a 73% identity. The 6 kDa and 12 kDa fragments generated by CNBr digestion of mouse liver GST 5.7 also gave sequences which matched with those of rat GST 8-8 between positions 106 and 120 and 167 and 186, with a high degree of identity. These studies suggest that mouse GST 5.7 structurally corresponds to rat GST 8-8 and belongs to the Alpha class. PMID- 1898366 TI - The importance of the negative charge of beta-lactam compounds in the interactions with active-site serine DD-peptidases and beta-lactamases. AB - The interaction between various penicillins and cephalosporins the carboxylate group of which at C-3 or C-4 had been esterified or amidated and different penicillin-recognizing enzymes was studied. In general, our findings reinforced the common assumption that an anionic group at that position is necessary for the effective acylation of these enzymes. However, the relative activities of the modified beta-lactams as inactivators of the Streptomyces R61 DD-peptidase or as substrates of the Bacillus licheniformis, Streptomyces albus G and Enterobacter cloacae beta-lactamases did not fit a general scheme in which the intrinsic electronic and geometric properties of the beta-lactam compounds would be sufficient to explain their substrate or inactivator properties towards the various types of enzymes investigated. PMID- 1898367 TI - Evidence that gene G7a in the human major histocompatibility complex encodes valyl-tRNA synthetase. AB - At least 36 genes have now been located in a 680 kb segment of DNA between the class I and class II multigene families within the class III region of the human major histocompatibility complex on chromosome 6p21.3. The complete nucleotide sequence of the 4.3 kb mRNA of one of these genes, G7a (or BAT6), has been determined from cDNA and genomic clones. The single-copy G7a gene encodes a 1265 amino-acid protein of molecular mass 140,457 Da. Comparison of the derived amino acid sequence of the G7a protein with the National Biomedical Research Foundation protein databases revealed 42% identity in a 250-amino-acid overlap with Bacillus stearothermophilus valyl-tRNA synthetase, 38.0% identity in a 993-amino-acid overlap with Escherichia coli valyl-tRNA synthetase (val RS), and 48.3% identity in a 1043-amino-acid overlap with Saccharomyces cerevisiae valyl-tRNA synthetase. The protein sequence of G7a contains two short consensus sequences, His-Ile-Gly His and Lys-Met-Ser-Lys-Ser, which is the typical signature structure of class I tRNA synthetases and indicative of the presence of the Rossman fold. In addition, the molecular mass of the G7a protein is the same as that of other mammalian valyl-tRNA synthetases. These features and the high sequence identity with yeast valyl-tRNA synthetase strongly support the fact that the G7a gene, located within the major histocompatibility complex, encodes the human valyl-tRNA synthetase. PMID- 1898368 TI - 5'-CMP stimulates phospholipase A-mediated hydrolysis of phosphatidylinositol in permeabilized pituitary GH3 cells. AB - We showed previously that 5'-CMP activates PtdIns-Ins base exchange and reversal PtdIns synthase in permeabilized rat pituitary GH3 cells. Here we report another effect of 5'-CMP on PtdIns metabolism in these cells. In permeabilized GH3 cells prelabelled with [3H]Ins and incubated in buffer with LiCl and a free Ca2+ concentration of 0.1 microM but without added Ins, 5'-CMP stimulated formation of glycerophospho[3H]inositol (GroP[3H]Ins) after a lag period of at least 5 min. This effect was concentration-dependent; the apparent Km was 0.30 +/- 0.02 mM. CDP and CTP stimulated GroPIns formation less effectively than did 5'-CMP, but cytidine, 2'-CMP, 3'-CMP, 5'-AMP and 5'-GMP had no effect. 5'-CMP stimulated formation of lysoPtdIns also. In permeabilized GH3 cells prelabelled with [3H]arachidonic acid, 5'-CMP stimulated release of [3H]arachidonic acid without a measurable lag period. These data show that 5'-CMP stimulates a phospholipase A activity in permeabilized GH3 cells that hydrolyses PtdIns. PMID- 1898369 TI - The kinetic mechanism catalysed by homogeneous rat liver 3 alpha-hydroxysteroid dehydrogenase. Evidence for binary and ternary dead-end complexes containing non steroidal anti-inflammatory drugs. AB - Rat liver 3 alpha-hydroxysteroid dehydrogenase (3 alpha-HSD) (EC 1.1.1.50) is an NAD(P)(+)-dependent oxidoreductase that is potently inhibited at its active site by non-steroidal anti-inflammatory drugs (NSAIDs). Initial-velocity and product inhibition studies performed in either direction at pH 7.0 are consistent with a sequential ordered Bi Bi mechanism in which pyridine nucleotide binds first and leaves last. This mechanism is supported by fluorescence titrations of the E-NADH complex, and by the failure to detect the binding of either [3H]androsterone or [3H]androstanedione to free enzyme by equilibrium dialysis. Dead-end inhibition studies with NSAIDs also support this mechanism. Initial-velocity studies with indomethacin show that this drug is an uncompetitive inhibitor against NAD+, but a potent competitive inhibitor against androsterone, indicating the ordered formation of an E.NAD+.indomethacin complex. Calculation of the individual rate constants reveals that the binding and release of pyridine nucleotide is rate limiting and that isomerization of the central complex is favoured in the forward direction. Equilibrium dialysis experiments with [14C]indomethacin reveal the presence of two abortive NSAID complexes, a high-affinity ternary complex corresponding to E.NAD+.indomethacin (Kd = 1-2 microM for indomethacin) and a low affinity binary complex corresponding to E.indomethacin (Kd = 22 microM for indomethacin). Since indomethacin has a low affinity for free enzyme, the formation of this abortive binary complex does not complicate kinetic measurements which are made in the presence of NAD+, but may contribute to the inhibition of the enzyme by NSAIDs. Using either pro-R-[4-3H]NADH or pro-S-[4 3H]NADH as cofactor, radiolabelled androsterone was formed only when the pro-R-[4 3H]NADH was used, confirming that purified 3 alpha-HSD is a Class A dehydrogenase. PMID- 1898370 TI - Comparison of the catalytic properties of phospholipase A2 from pancreas and venom using a continuous fluorescence displacement assay. AB - Phospholipases A2 from pig pancreas and the venoms from bee, Naja naja and Crotalus atrox have been studied by using a new continuous fluorescence displacement assay that utilizes normal phospholipid substrates [Wilton (1990) Biochem. J. 266, 435-439]. With limiting amounts of substrate, the assay demonstrated stoichiometric conversion into products with both pancreatic and venom enzymes, and thus would allow phospholipid determination at concentrations down to about 0.1 microM. The substrate specificity of the enzyme was determined for the four enzymes in terms of both phospholipid head group and fatty acid selectivity. None of the enzymes demonstrated a preference for arachidonic acid containing phospholipid under the conditions of this assay. No lag was observed with any enzyme with either phosphatidylcholine or phosphatidylglycerol as substrate. With dipalmitoyl-phosphatidylcholine as substrate, the assay clearly highlighted the different membrane-penetrating properties of the pancreatic and Naja naja enzymes and demonstrated maximal activity for the pancreatic enzyme in the region of the phase-transition temperature of this substrate, at about 35 degrees C. PMID- 1898371 TI - Distribution of manganese in rat pancreas and identification of its primary binding protein as pro-carboxypeptidase B. AB - Distribution of manganese (Mn) and its binding to specific proteins were examined in rat pancreas. A MnCl2 solution was injected subcutaneously into Wistar rats daily at a single dose of 15 mg of Mn/kg body weight for 10 days and the animals were killed 1 day after the last injection. The concentration of Mn in the pancreas increased considerably from 1.4 +/- 0.2 (control) to 13.3 +/- 3.7 micrograms/g wet tissue by the repeated injection of Mn. The distribution of Mn in the soluble fraction of the pancreas (170,000 g supernatant) was determined on a gel-filtration column (Asahipak GST-520) using an h.p.l.c.-inductively coupled argon plasma atomic-emission spectrometry (i.c.p.) technique. The metal was eluted as a single peak in the high-molecular-mass protein fraction, where Mn had been observed as a small peak in the control profile, suggesting that the administered Mn was bound to the same Mn-binding component as that in the control. On the basis of enzymic and chemical characterization of the protein, it was identified as a zymogen of carboxypeptidase B (pro-carboxypeptidase B, pro CPB). The elution profiles of the protein by h.p.l.c.-i.c.p. indicated that Mn and zinc (Zn) were bound to the zymogen with a molar ratio of 1:4 in normal rat pancreas. Mn bound to the zymogen was easily replaced by Zn in vitro, suggesting that Mn was bound to the Zn-binding site and that the binding affinity to Zn was higher than that to Mn. The present results indicate that pro-CPB is the primary Mn-binding protein in the pancreas of control and also Mn-administered rats. PMID- 1898372 TI - Endothelial cell growth factor and heparin regulate collagen gene expression in keloid fibroblasts. AB - Keloids are benign cutaneous tumours characterized by excess deposition of collagen, specifically type I collagen. We report here that collagen biosynthesis, as measured by hydroxyproline synthesis, was markedly inhibited by 65-80% by the combination of endothelial cell growth factor (ECGF) supplement and heparin in keloid fibroblast cultures. Fibroblast cultures that were incubated with ECGF alone also demonstrated a measurable decrease of approx. 50% in collagen synthesis compared with control cultures. The inhibition of collagen synthesis was related to the down-regulation of collagen gene expression. Quantitative measurements of mRNA-cDNA hybrids revealed that the gene expression of collagen type I was decreased by more than 80% by heparin and ECGF. Markedly diminished levels of mRNA encoding collagen type I were also observed in cultures incubated with ECGF alone. The results show that ECGF and heparin elicit a negative regulatory effect on collagen production, and that this inhibition is due largely to the down-regulation of the pro-alpha 1(I) of type I collagen gene. Furthermore, ECGF has a potent suppressive effect, and heparin provides an additive effect to this inhibitory phenomenon. PMID- 1898373 TI - Levels of ornithine decarboxylase genomic sequences, heterogeneous nuclear RNA and mRNA in human myeloma cells resistant to alpha-difluoromethylornithine. AB - We previously isolated and characterized a human myeloma cell line overproducing ornithine decarboxylase (ODC) due to gene amplification [Leinonen, Alhonen Hongisto, Laine, Janne & Janne (1987) Biochem. J. 242, 199-203]. We have now employed the PCR combined with reverse transcription to determine semiquantitatively ODC gene dosage and the amounts of heterogeneous nuclear (hn) RNA and of mature mRNA of the enzyme in parental and alpha difluoromethylornithine-resistant human myeloma cells. Experiments with dilution series revealed that the ODC gene copy number and the amount of both hnRNA and mRNA were increased to the same extent (about 100-fold) in the resistant cells. Similar dot-blot analyses of ODC-specific genomic DNA and total RNA indicated that the ODC gene copy number was increased by a factor of 380 and the amount of ODC mRNA by a factor of 700. Our results indicate that the PCR combined with reverse transcription is at least as useful as blot analyses to give semiquantitative assessment of the amounts of specific DNA or RNA sequences. In addition, the use of the PCR enables the analysis of minute sample amounts in extremely short time. PMID- 1898374 TI - Re-evaluation of the glycerol-3-phosphate dehydrogenase/L-lactate dehydrogenase enzyme system. Evidence against the direct transfer of NADH between active sites. AB - An investigation of the direct transfer of metabolites from rabbit muscle L lactate dehydrogenase (LDH, EC 1.1.1.27) to glycerol-3-phosphate dehydrogenase (GPDH, EC 1.1.1.8) revealed discrepancies between theoretical predictions and experimental results. Measurements of the GPDH reaction rate at a fixed NADH concentration and in the presence of increasing LDH concentrations gave experimental results similar to those previously obtained by Srivastava, Smolen, Betts, Fukushima, Spivey & Bernhard [(1989) Proc. Natl. Acad. Sci. U.S.A. 86, 6464-6468]. However, a mathematical solution of the direct-transfer-mechanism equations as described by Srivastava et al. (1989) showed that the direct transfer model did not adequately describe the experimental behaviour of the reaction rate at increasing LDH concentrations. In addition, experiments designed to measure the formation of an LDH4.NADH.GPDH2 complex, predicted by the direct transfer model, indicated that no significant formation of tertiary complex occurred. An examination of other kinetic models, developed to describe the LDH/GPDH/NADH system better, revealed that the experimental results may be best explained by assuming that free NADH, and not E1.NADH, is the sole substrate for GPDH. These results suggest that direct transfer of NADH between rabbit muscle LDH and GPDH does not occur in vitro. PMID- 1898376 TI - Characterization of a transgenic mouse line over-expressing the human ornithine decarboxylase gene. AB - We have produced several transgenic mouse lines over-expressing the human ornithine decarboxylase (ODC) gene. We have now characterized one of the transgenic lines as regards the tissue accumulation of the polyamines and the activities of their metabolizing enzymes. Among the tissues analysed, the polyamine pattern was most strikingly changed in testis and brain of the transgenic animals. ODC activity was greatly enhanced in all tissues, except kidney, of the transgenic animals. The most dramatic increase, 80-fold, was found in brain of the transgenic mice. The activities of S-adenosylmethionine decarboxylase and spermidine and spermine syntheses were likewise significantly increased in testis of the transgenic animals. The activities of the enzymes involved in the back-conversion of the polyamines, namely spermidine/spermine acetyltransferase and polyamine oxidase, were similar in the transgenic and non transgenic animals. As analysed by reverse transcriptase/polymerase chain reaction, all the six tissues of the transgenic animals expressed human-specific ODC mRNA. Determination of the half-life of testicular ODC revealed a stabilization of the enzyme in the transgenic males. PMID- 1898375 TI - Hydrolysis of thymic humoral factor gamma 2 by neutral endopeptidase (EC 3.4.24.11). AB - A search for the natural substrates for neutral endopeptidase (NEP; EC 3.4.24.11) in the immune system led to investigation of the enzyme's action on thymic humoral factor gamma 2 (THF). The ectoenzyme rapidly and efficiently hydrolyses the Lys6-Phe7 bond of the octapeptide. The site of cleavage was confirmed by h.p.l.c. analysis, amino acid analysis and sequence determination of the products. Phosphoramidon (3.6 microM), a potent inhibitor of the enzyme, prevents this cleavage even during prolonged incubation. The high efficiency of hydrolysis of THF by NEP is similar to that reported for [Leu5]enkephalin, and the dipeptide Phe-Leu is the C-terminal product in the hydrolysis of both peptides. The presence of NEP, reportedly identified as the common acute lymphoblastic leukaemia antigen (CALLA), in bone-marrow cells and other cells of the immune system raises the possibility that it may play a role in modulating the activity of peptides such as THF. PMID- 1898378 TI - Action of uroporphyrinogen decarboxylase on uroporphyrinogen-III: a reassessment of the clockwise decarboxylation hypothesis. PMID- 1898377 TI - An optimized assay of phosphorylase kinase in crude liver preparations. PMID- 1898379 TI - Action of uroporphyrinogen decarboxylase on uroporphyrinogen III. PMID- 1898380 TI - Inhibition of adenylate cyclase by Ca(2+)--a counterpart to stimulation by Ca2+/calmodulin. PMID- 1898381 TI - Characterization of a new bioactive protein from bovine seminal fluid. AB - A new acidic seminal fluid protein (aSFP) was purified from bovine seminal fluid, using anion exchange chromatography and FPLC on MonoQ. The purified aSFP displays a pI of 4.8 and an apparent molecular weight of 14 kDa. Homogeneity of aSFP was demonstrated by FPLC and SDS-polyacrylamide gel electrophoresis. Monospecific anti-aSFP IgGs were employed to characterize aSFP in bovine seminal plasma and seminal vesicle secretion by immuno blot analysis. Proteinchemical characterization of aSFP included amino acid analysis as well as determination of 23 amino acid residues of the N-terminal sequence of aSFP. According to this sequence, aSFP appears to represent a hitherto unknown protein. aSFP stimulated cell division and progesterone secretion of bovine granulosa cells in vitro in a potent and dose dependent manner. aSFP appears to be a potent growth factor with effects on ovarian granulosa cells. PMID- 1898382 TI - The influence of L-NG-nitro-arginine on field stimulation induced contractions and acetylcholine release in guinea pig isolated tracheal smooth muscle. AB - The interaction between parasympathetic and inhibitory non-adrenergic, non cholinergic nerves in tracheal smooth muscle was investigated by determining the effects of the NO-synthase inhibitor L-NG-nitro-arginine (L-NOARG) on contractions and the associated acetylcholine release elicited by field stimulation of the muscle. At frequencies above 2Hz contractile responses to field stimulation were potentiated by L-NOARG (50 microM). alpha-chymotrypsin pre treatment potentiated contractile responses at all frequencies, but the effects of L-NOARG were unaltered. The effect of L-NOARG on responses to 5Hz electrical stimulation was not mimicked by D-NOARG, was reversed by L-, but not D-arginine and was unaffected by epithelium removal. L-NOARG did not affect responses to exogenous acetylcholine nor the overflow of 3H from tissues previously loaded with [3H]-choline. It is therefore concluded that field stimulation of tracheal smooth muscle induces the release of an endogenous nitrate, which, by an inhibitory action on smooth muscle, functionally antagonises the concomitantly released parasympathetic neurotransmitter. PMID- 1898383 TI - Age-associated accumulation of 8-hydroxydeoxyguanosine in mitochondrial DNA of human diaphragm. AB - This is the first report that age-associated accumulation of 8 hydroxydeoxyguanosine (8-OH-dG) does occur in human mitochondrial DNA (mtDNA) in muscle of diaphragm. We extracted mtDNA from human diaphragm muscles from differing age groups, and determined the amount of 8-OH-dG by ultramicro-high performance liquid chromatography/mass-spectrometry system. With the same specimen, multiple deletions of mtDNA were detected by electrophoresis after amplification by the polymerase chain reaction method. In subjects below age 55, the level of 8-OH-dG in mtDNA was below 0.02% of the total deoxyguanosine (dG), whereas, in subjects over age 65, the level of 8-OH-dG increased with age at a rate of ca. 0.25% per 10 years, reaching 0.51% at age 85. Moreover, a concomitant increase in multiple deletions was detected with the increase in age. These results suggest that, in younger diaphragms, replication of mtDNA dilutes out 8 OH-dG being not detectable. In the elderly subjects aged over 65, the replication rate might be slowed down leading to the accumulation of 8-OH-dG in mtDNA, which would accelerate the age-associated multiple deletions of mtDNA observed among the subjects. PMID- 1898384 TI - Increment of alpha B-crystallin mRNA in the brain of patient with infantile type Alexander's disease. AB - To estimate the expression level of alpha B-crystallin in the brain of infantile type Alexander's disease, the amounts of protein and mRNA of alpha B-crystallin were measured by enzyme immunoassay (EIA) and Northern blot analysis, respectively, in the brain of patient and controls, and in the tissues from glioblastoma and astrocytoma. The alpha B-crystallin protein in the brain of patient was remarkably increased as compared with those of controls. The amount of alpha B-crystallin mRNA of patient was increased about 7-fold compared to the mean value of the control group and higher than that of glioblastoma tissue. These data suggest that increment of alpha B-crystallin mRNA in astrocytes leads to the overexpression of this protein and may be one of the main causes of infantile type Alexander's disease. PMID- 1898385 TI - Modification of the N-terminus of membrane fusion-active peptides blocks the fusion activity. AB - The amphiphilic anionic peptides E5 and E5L can mimic the fusogenic activity of influenza hemagglutinin(HA). These peptides induced fusion of egg yolk phosphatidylcholine small or large unilamellar vesicles only at acidic pH in a similar manner to viral HA. Acetylation or acetimidylation of the N-terminus of the peptides drastically reduced the fusion activity of the intact peptides, while C-terminal amidation left the activity unchanged. The binding assay suggested that the interaction of the modified peptides with lipid membranes was almost unchanged in comparison with those of the parent peptides, and the CD spectra showed that these peptides were alpha-helical. The results showed the importance of the N-terminus of the peptides on the membrane fusion activity, although why the N-terminal modifications affect the activity is still unclear. PMID- 1898386 TI - Protein and DNA-sequence homologies between the V3-loop of human immunodeficiency virus type I envelope protein gp120 and immunoglobulin variable regions. AB - We found that a common amino acid sequence motif exists between the V3-loop region of the human immunodeficiency virus type I envelope protein HIV gp120 and the human immunoglobulin heavy chain variable regions of subclass III (Ig VH III). In the Ig VH-III sequences, the common motif overlaps with framework-1, complementarity-determining-region-1 and framework-2. In the homologous regions, the two groups of sequences also have a similar distribution of residue variability. On the DNA sequence level, the homology includes the conserved rearrangement signals of the VH-III genes, which lends support to the speculation that the V3 region of gp120 also may be involved in rearrangement processes. PMID- 1898388 TI - Inhibitory effect of phosphatidylserine on iron-dependent lipid peroxidation. AB - The effect of phospholipids on lipid peroxidation was investigated in liposomal suspension of egg yolk phosphatidylcholine. Both saturated and unsaturated phosphatidylserine effectively inhibited lipid peroxidation induced by ferrous ascorbate system in the presence of phosphatidylcholine hydroperoxides. Studies on the iron trapping effect of phospholipids indicated that the effectiveness of inhibition depends on the charge of phosphatidylserine that binds to free ionic iron. PMID- 1898387 TI - Phospholipase D in cultured rat vascular smooth muscle cells and its activation by phorbol ester. AB - We determined the phospholipase D (PLD) activity in rat vascular smooth muscle cells by the formation of phosphatidylethanol in cells prelabeled with [3H] myristic acid. The enzyme was markedly activated by a phorbol ester (TPA). Down regulation of protein kinase C (PKC) resulted in almost complete inhibition indicating PKC-dependent mechanism of its activation. Depletion of calcium by EGTA and TMB-8 caused 53% inhibition. Chelator-stable association of PKC to membrane by TPA was observed in the absence of extracellular Ca2+. The mitogenic peptide PDGF also caused a marked stimulation of PLD. These results indicate that PLD in vascular smooth muscle cells is stimulated by TPA through the activation of PKC both by calcium-dependent and independent mechanisms. PMID- 1898389 TI - Developmental changes in the organization of the nuclear lamina in mouse liver. AB - We have compared the organization of the nuclear lamina in adult and fetal mouse liver. Western blot analysis of the expression of lamins with specific antibodies indicates that lamin B is expressed throughout liver development, unlike lamins A and C which are absent in fetal liver. Using [125I]lamin in blot binding assays, we have observed that lamin B binds to at least three membrane proteins (96, 54 and 34 kDa) and to lamins A and C in adult nuclear envelopes, but only to the 54 and 34 kDa proteins and lamin B itself in fetal nuclear envelopes, where lamin B appears to be hyperphosphorylated. PMID- 1898390 TI - Possible involvement of a L-delta 1-pyrroline-5-carboxylate (P5C) reductase in the synthesis of proline in Desulfovibrio desulfuricans Norway. AB - A L-delta 1-pyrroline-5-carboxylate reductase activity has been detected in crude extracts of Desulfovibrio desulfuricans Norway. This P5C reductase activity is also found when a 2.5 kb D. desulfuricans DNA fragment is introduced into an Escherichia coli proC mutant. Although it restores growth of the proC mutant, the ProDd enzyme might be detrimental to the E. coli host since the plasmid carrying the cognate proDd gene is segregated at high rate by the cells but is stabilized by small deletions which lead to a loss of the P5C reductase activity. PMID- 1898391 TI - Separation of Escherichia coli RNA polymerase sigma-70 holoenzyme from core enzyme on heparin-Sepharose columns. AB - A method is described for the rapid purification of DNA-dependent RNA polymerase sigma-70 holoenzyme from Escherichia coli. The essential step in this protocol involves the differential elution of sigma-70 holoenzyme from core polymerase on a heparin-Sepharose column. Using a linear gradient of KCl, holoenzyme was found to elute at 0.25 M whereas core polymerase eluted at 0.35 M. From 20 g of cells, up to 1 mg of RNA polymerase holoenzyme could be isolated in two days. The preparations were greater than 95% pure with respect to protein, and saturated with the sigma subunit. PMID- 1898392 TI - Pachytene spermatocytes can achieve meiotic process in vitro. AB - Highly enriched pachytene spermatocytes prepared from adult rats by centrifugal elutriation were tested for their capacity to enter the meiotic process when cocultured with 20-day old rat Sertoli cells. This was traced by phase-contrast microscopy and by DNA flow cytometry. We also performed a Northern blot analysis using the mouse protamine I cDNA as a probe, the expression of which being restricted to spermatids. Our results demonstrate that pachytene spermatocytes cocultured with Sertoli cells developed into spermatids. The number of pachytene spermatocytes entering meiosis was affected neither by growth factors nor by hormones. However these later were required in long term cocultures for the maintenance of cell integrity and viability. PMID- 1898393 TI - Comparison of the hemodynamic effects of endothelin-1 and big endothelin-1 in the rat. AB - We compared the hemodynamic effects of continuous i.v. infusion of endothelin-1 and big endothelin-1 in anesthetized rats. Big endothelin-1 was fivefold less potent than endothelin-1 in decreasing cardiac output, heart rate, and stroke volume. However, big endothelin-1 produced a significantly larger increase in mean arterial pressure compared to endothelin-1 at doses that produced identical decreases in cardiac output. These findings support the hypothesis that the hypertensive effects of big endothelin-1 and endothelin-1 are produced by differential effects on systemic vascular resistances. PMID- 1898394 TI - N,N-diethylhydroxylamine: a new electron donor to photosystem II. AB - Diethylhydroxylamine, when added to beet spinach thylakoid membranes in the reaction mixture enhanced both photosystem II mediated dichlorophenolindophenol photoreduction and whole chain electron transport supported by methyl viologen. Diethylhydroxylamine supports dichlorophenolindophenol photoreduction when oxygen evolving complex is inactivated by hydroxylamine washings. All the electron transport assays were found to be highly sensitive to diuron, indicating that diethylhydroxylamine donates electrons to the photosystem II before the herbicide binding site. The stimulation of the photochemical activity by diethylhydroxylamine is not solely due to its action as an uncoupler. It was also observed that the action of diethylhydroxylamine was not altered by preincubations of thylakoids in light in the presence of diethylhydroxylamine. Also, thylakoid membranes did not lose their benzoquinone Hill activity by the pre-incubations with diethylhydroxylamine either in light or in dark. Thus, unlike the photosystem II electron donor, hydroxylamine, diethylhydroxylamine was found to donate electrons without the inactivations of oxygen evolving complex. It is suggested that diethylhydroxylamine is a useful electron donor to the photosystem II. PMID- 1898395 TI - Occurrence of autoimmune antibodies to liver microsomal proteins in association with fulminant hepatitis in the LEC strain of rats. AB - The Long Evans Cinnamon (LEC) rat, which has been established as a strain showing hereditary hepatitis and hepatic carcinoma, was found to possess autoimmune antibodies to liver microsomal proteins, particularly to a protein with the molecular weight of 56kD. The antibodies also recognized a protein(s) in liver microsomes from Long Evans Agouti and Sprague-Dawley rats. About 42 and 15 percent of respective female and male LEC rats died within a week after acute hepatitis; sera from all of the animals contained the antibodies. About 43 and 0 percent of the surviving female and male LEC rats possessed the antibodies, respectively. These results suggest that the autoantibodies occur in association with acute lethal hepatitis in the LEC rats. PMID- 1898396 TI - The protein kinase C inhibitor 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7) inhibits PMA-induced promiscuous cytolytic activity but not specific cytolytic activity by a cloned cytolytic T lymphocyte. AB - Phorbol 12-myristate 13-acetate (PMA) induces the cytolytic T lymphocyte (CTL) clone 4D (H-2b anti-H-2d) to promiscuously kill the inappropriate target EL-4 (H 2b). The protein kinase C (PKC) inhibitor 1-(5-isoquinolinesulfonyl)-2 methylpiperazine dihydrochloride (H-7) inhibited the PMA-induced promiscuous lympholysis. The concentration of H-7 that inhibited PMA-induced lympholysis by 50% (IC50) was calculated to be 4 microM, which closely approximates the reported IC50 of H-7 of 6 microM for PKC activity in vitro. In striking contrast, specific cytolysis of appropriate P815 (H-2d) target cell by CTL clone 4D was not inhibited by concentrations of H-7 which inhibited PMA-induced promiscuous lympholysis. These results indicate that PMA-induced promiscuous lympholysis of inappropriate target cell is triggered via activation of PKC, whereas PKC activation is not obligatory in triggering CTL clone 4D to specifically kill appropriate target cells. Thus, these data suggest that cloned CTL have two or more triggering mechanisms than may initiate one or more cytolytic pathways. PMID- 1898397 TI - The effect of vitamin D on rat intestinal plasma membrane CA-pump mRNA. AB - The effects of vitamin D on steady-state levels of rat intestinal Ca-pump mRNA were examined in RNA extracted from isolated cell fractions of the crypt-to villus gradient of differentiation. Northern blots revealed three different size mRNAs. Vitamin D deficient animals showed a decrease in these Ca-pump mRNAs, which increased markedly after 1,25-(OH)2D3 repletion, particularly for the villus cell. The data suggest that one of the effects of 1,25-(OH)2D3 may be to modulate enterocyte Ca-pump mRNA and that this effect is partly dependent on the stage of cell differentiation. PMID- 1898398 TI - Binding of radioiodinated SPECT ligands to transfected cell membranes expressing single muscarinic receptor subtypes. AB - The equilibrium dissociation constant and the kinetic rate constants were determined for the binding of (R)-[3H]3-quinuclidinyl benzilate ([3H]QNB) and [125I]3-quinuclidinyl-4-iodobenzilate ((R,R)- and (R,S)-[125I]IQNB) to transfected cell membranes expressing one single muscarinic acetylcholine receptor (mAChR) subtype. The association and dissociation kinetics for the m2 subtype were more rapid than for the m1 and m3 subtypes. The differential kinetic properties may be useful for the single photon emission computed tomographic (SPECT) evaluation of regional mAChR subtype alterations in disease states. PMID- 1898400 TI - Molecular characterization of the interleukin-8 receptor. AB - Recently a rabbit cDNA (F3R) was characterized as binding and causing calcium mobilization induced by the formyl-methionine-leucine-phenylalanine peptide (fMLP). In the study reported here, cloned DNAs were isolated from rabbit genomic DNA by PCR based on the sequence of F3R. The cloned DNAs have several differences in the DNA sequence compared to the reported F3R sequence that alter the predicted protein sequence. COS-7 cells transfected with these clones in a mammalian expression vector bind human IL-8 with high affinity, but do not bind fMLP. We therefore believe that the cDNAs isolated encode the rabbit IL-8 receptor. PMID- 1898399 TI - The 5'-triphosphates of 3'-azido-3'-deoxythymidine and 2', 3'-dideoxynucleosides inhibit DNA polymerase gamma by different mechanisms. AB - Inhibition mechanisms of 5'-triphosphates of 3'-azido-3'-deoxythymidine (AZT-TP) and 3'-deoxythymidine (ddTTP) on extensively purified DNA polymerase gamma from bovine testes were examined by analysis of the products synthesized on singly primed M13 single-stranded DNA or synthetic oligonucleotide template-primer in the presence of analogues. The results indicate that AZT-TP inhibits DNA polymerase gamma in competition with dTTP but is not incorporated into DNA, whereas ddTTP is incorporated into DNA and causes chain termination. In contrast, both analogues were used by reverse transcriptase and caused chain termination. PMID- 1898401 TI - Role of cysteine residues in the activity of rat glutathione transferase P (7-7): elucidation by oligonucleotide site-directed mutagenesis. AB - To clarify the role(s) of thiol (sulfhydryl) groups of cysteine (Cys) residues in the activity of the rat glutathione transferase P (7-7) form (GST-P), a cDNA clone, pGP5, containing the entire coding sequence of GST-P (Y. Sugioka et al., (1985) Nucleic Acids Res. 13, 6044-6057) was inserted into the expression vector pKK233-2 and the recombinant GST-P (rGST-P) expressed in E. coli JM109. All four Cys residues in rGST-P were independently substituted with alanine (Ala) by site directed mutagenesis, the resultant mutants as well as the rGST-P being identical to GST-P purified from liver preneoplastic nodules with regard to molecular weight and immunochemical staining. Since all mutants proved as enzymatically active towards 1-chloro-2,4-dinitrobenzene as liver GST-P, it was indicated that none of the four Cys residues is essential for GST-P activity. However, the mutant with Ala at the 47th position from the N-terminus (Ala47) became resistant to irreversible inactivation by 0.1 mM N-ethylmaleimide (NEM), whereas the other three mutants remained as sensitive as the nonmutant type (rGST-P). Ala47 was also resistant to inactivation by the physiological disulfides, cystamine or cystine, which cause mixed disulfide and/or intra- or inter-subunit disulfide bond formation. These results suggest that the 47-Cys residue of GST-P may be located near the glutathione binding site, and modulation of this residue by thiol/disulfide exchange may play an important role in regulation of activity. PMID- 1898402 TI - Protection by acidotic pH against anoxia/reoxygenation injury to rat neonatal cardiac myocytes. AB - We assessed the effect of acidosis on cell killing during anoxia and reoxygenation in cultured rat neonatal cardiac myocytes. After 4.5 hours of anoxia and glycolytic inhibition with 2-deoxyglucose, loss of viability was greater than 90% at pH 7.4. In contrast, at pH 6.2-7.0, viability was virtually unchanged. To model changes of pH and oxygenation during ischemia and reperfusion, myocytes were made anoxic at pH 6.2 for 4 hours, followed by reoxygenation at pH 7.4. Under these conditions, reoxygenation precipitated loss of viability to about half the cells. When pH was increased to 7.4 without reoxygenation, similar lethal injury occurred. No cell killing occurred after reoxygenation at pH 6.2. We conclude that acidosis protects against lethal anoxic injury, and that a rapid return from acidotic to physiologic pH contributes significantly to reperfusion injury to cardiac myocytes - a 'pH paradox'. PMID- 1898404 TI - Neutron scattering studies of chromatosomes. AB - Neutron scattering data establish that the radius of gyration of the DNA in chicken erythrocyte chromatosome particles is significantly higher, by about 0.3 nm, than the radius of gyration of the DNA in the core particle. Corresponding information of the radius of gyration of the protein component in the chromatosomes (3.75 nm) indicated an enlargement, compared to the radius of gyration of the octamer of histone proteins both in core particles and in the histone octamer stabilised in 2 M NaCl (3.25 nm). From the latter data, we could calculate the distance in the chromatosome between the centre of mass of the linker histone and the histone octamer as 5.5 nm. These results impose severe limitations for the organisation of the 22 bp extra DNA and the possible location of H1/H5 in the chromatosome, implying that the H1/H5 is close to the centre turn of the core particle DNA. PMID- 1898403 TI - Preparation and crystallization of human transthyretin (prealbumin) variants. AB - Naturally occurring variants of human serum transthyretin (prealbumin) have been prepared by recombinant DNA methods and crystallized from ammonium sulfate solutions to give crystals suitable for x-ray crystallographic analysis. Included are variants which are known to be associated with familial amyloidotic polyneuropathy. Dyes which have been used as histochemical stains to identify amyloid tissue deposits: Congo Red, Methylene Blue and Bromophenol Blue, have been co-crystallized with the transthyretin variants. Congo Red was found to be very selective while Methylene Blue actually assisted in the formation of crystals. All crystal forms which were examined were isomorphous to the structure of normal transthyretin. PMID- 1898405 TI - Different effects of DNA adducts induced by carcinogenic and noncarcinogenic azo dyes on in vitro DNA synthesis. AB - M13mp10 phage DNA modified with the carcinogen 3-methoxy-4-aminoazobenzene (3-MeO AAB) or the noncarcinogen 2-methoxy-4-aminoazobenzene (2-MeO-AAB) was used as a template for E.coli DNA polymerase I. Analysis of the reaction products on DNA sequencing gels showed that with both types of compound the induced lesions blocked DNA synthesis, mainly at one base prior to guanine adducts, but that the inhibition by 3-MeO-AAB-adducts was substantially greater than that by 2-MeO-AAB adducts. Thus different effects on DNA replication between 3-MeO-AAB- and 2-MeO AAB-adducts might be a reflection of differences in their carcinogenic potency. PMID- 1898406 TI - Local formation and degradation of endothelin-1 in guinea pig airway tissues. AB - Endothelin(ET)-1 and big ET-1 caused potent and sustained constriction of isolated guinea pig bronchus. The response to ET-1 was enhanced by phosphoramidon in a simple dose-related manner (0.01-1000 microM), while the response to big ET 1 was enhanced at lower doses (0.01-0.1 microM) but was suppressed at higher doses (100-1000 microM) of phosphoramidon. Big ET-1, when given intravenously (i.v.) to anesthetized guinea pigs, increased both bronchopulmonary inflation pressure and mean arterial blood pressure (2.5, 5, 10 nmol/kg i.v.). The pressor response to big ET-1 was attenuated by phosphoramidon dose-relatedly, while the pulmonary response was modified in a complex fashion composed of delayed onset and prolonged duration of action. These results suggest that ET converting as well as degrading enzymes coexist in the airway tissue and both enzymes are sensitive to phosphoramidon, so that phosphoramidon acts bifunctionally to reduce and stimulate the airway responses to big ET-1. PMID- 1898408 TI - Effect of hyperbaric oxygenation on macrophage function in mice. AB - Hyperbaric oxygenation (HBO) has an immunosuppressive effect. The possible mechanisms of this immunosuppressive effect were assessed by determining the production of interleukin-1 (IL-1), interleukin-6 (IL-6), and prostaglandin E2 (PGE2), as well as phagocytosis by splenic macrophages from HBO-treated mice. Although HBO treatment did not have any significant effect on IL-6 production and phagocytotic activity, a marked decrease in IL-1 production and a significant decrease in PGE2 production were observed. These results suggest that the reduction of IL-1 production may play an important role in the immunosuppressive effect of HBO. PMID- 1898409 TI - Hydrogenosomal succinate thiokinase in Tritrichomonas foetus and Trichomonas vaginalis. AB - Succinate thiokinase displays a diversity of nucleotide specificity and molecular size throughout Nature. Eukaryotes and Gram-positive bacteria possess distinct 'small' (dimeric) thiokinase enzymes which are specific for adenine (ADP) or guanine (GDP) nucleotides, whereas Gram-negative bacteria contain a single 'large' (tetrameric) enzyme which utilizes both nucleotides. Succinate thiokinase activities, both ADP- and GDP-dependent, were shown to be hydrogenosomal in Tritrichomonas foetus and Trichomonas vaginalis. Surprisingly, the 'small' enzyme was found in T. foetus whereas T. vaginalis contained a 'large' enzyme. PMID- 1898407 TI - Bacterial toxins induce heat shock proteins in human neutrophils. AB - We studied the influence of different bacterial toxins (alveolysin; toxic shock syndrome toxin 1, TSST-1 and erythrogenic toxin A, ETA) on the expression of heat shock proteins (hsps) in isolated human polymorphonuclear granulocytes (PMNs). As was shown by Western blotting (anti-hsp72) ETA and TSST-1 were potent inducers of hsps at low toxin concentrations (10 ng/ml). Alveolysin led to the expression of hsps at hemolytic concentrations (1 HU; 700 ng/ml) whereas at subhemolytic concentrations (7 ng/ml) no heat shock response was observed. The induction of heat shock proteins was also accompanied by increased mRNA levels for hsp70 as was determined by PCR-analysis. PMID- 1898410 TI - Heterologous expression of active manganese peroxidase from Phanerochaete chrysosporium using the baculovirus expression system. AB - The cDNA encoding Mn peroxidase isozyme H4 from Phanerochaete chrysosporium was recombined into a baculovirus and heterologously expressed in Sf9 cells. The recombinant Mn peroxidase has the same molecular weight as the native enzyme as determined by SDS-PAGE and cross-reacts with a Mn peroxidase-specific antibody. The recombinant enzyme has a slightly lower pI than the native fungal isozyme H4 indicating some differences in post-translational modification. Phenol red, guaiacol, and vanillylacetone, substrates of the native Mn peroxidase, are oxidized by the recombinant enzyme. All of the activities are dependent on both Mn (II) and H2O2. PMID- 1898411 TI - 1H-NMR studies of lipid extracts of rat liver mitochondria. AB - Lipid extracts of rat liver mitochondria were studied by 1H-NMR at 200 MHz. Each spectrum, obtained in 6 min with routine acquisition parameters, allowed the estimation of the phosphatidylcholine/phosphatidylethanolamine ratio, the cholesterol/total lipid molar ratio, the average fatty acid length, the unsaturation ratio and the oxidation state of the ubiquinone/ubiquinol couple. 1H NMR spectroscopy was also used to analyze structural changes of the lipids following peroxidation. In model liposomes subjected to enzymatic peroxidation the appearance of hydroperoxides and conjugated double bonds were detected, whereas in mitochondria no such changes were seen even after a period of relatively high oxidative stress. This suggests that the systems for protection against oxidative damage in mitochondria are able to keep the amount of peroxidation products below the detection limit of the technique. PMID- 1898412 TI - Transmembrane signalling by insulin via an insulin receptor mutated at tyrosines 1158, 1162, and 1163. AB - In order to study the role of tyrosine autophosphorylation in insulin receptor signalling, we investigated a mutant human insulin receptor whereby the three major tyrosine autophosphorylation sites at positions 1158, 1162, and 1163 in the receptor beta-subunit were mutated to phenylalanines. When these mutant receptors were expressed in HTC rat hepatoma cells, there was no enhanced beta-subunit autophosphorylation and tyrosine kinase activity. In these cells there was enhanced insulin stimulation of [3H]AIB uptake and [3H]thymidine incorporation when compared to wild type HTC cells. The present study suggests therefore that the presence of the major insulin autophosphorylation sites is not a requirement for insulin stimulation of amino acid transport and mitogenesis. PMID- 1898413 TI - Identification of a point mutation in the human lysosomal alpha-glucosidase gene causing infantile glycogenosis type II. AB - Two patients in a consanguineous Indian family with infantile glycogenosis type II were found to have a G to A transition in exon 11 of the human lysosomal alpha glucosidase gene. Both patients were homozygous and both parents were heterozygous for the mutant allele. The mutation causes a Glu to Lys substitution at amino acid position 521, just three amino acids downstream from the catalytic site at Asp-518. The mutation was introduced in wild type lysosomal alpha glucosidase cDNA and the mutant construct was expressed in vitro and in vivo. The Glu to Lys substitution is proven to account for the abnormal physical properties of the patients lysosomal alpha-glucosidase precursor and to prevent the formation of catalytically active enzyme. In homozygous form it leads to the severe infantile phenotype of glycogenosis type II. PMID- 1898414 TI - The toxic moiety of the Bacillus thuringiensis protoxin undergoes a conformational change upon activation. AB - Proteolytic processing of the 133-kDa crystal protein (protoxin) from Bacillus thuringiensis subsp. kurstaki yields a 67-kDa insecticidal toxin. Differential scanning calorimetry was used to investigate whether the toxic moiety in the protoxin molecule has the same conformation as activated toxin. Compared to protoxin, toxin gives rise to a more complex endotherm which extends over a 10 degrees C broader temperature range and contains a component occurring at a substantially higher temperature than any unfolding transition in the protoxin endotherm. It is concluded that the toxic moiety undergoes a conformational change upon activation in which the thermal stability of at least one of its domains is significantly increased. PMID- 1898415 TI - In vivo oxygen-17 nuclear magnetic resonance for the estimation of cerebral blood flow and oxygen consumption. AB - To explore the feasibility of in vivo 17O NMR for the estimation of cerebral blood flow and oxygen consumption, in vivo 17O NMR spectroscopy and imaging were employed in animal models. In the spectroscopy, the changes in the 17O NMR signal intensity after the injection of H2(17)O and the inhalation of 17O2 gas were obtained every 4 seconds with sufficient signal-to-noise ratios for the quantification of cerebral blood flow and oxygen consumption. In the imaging, although the time and spatial resolutions were insufficient for the quantification of H2(17)O, 17O NMR images of rabbit brain could be obtained, indicating that it is possible to map cerebral blood flow and oxygen consumption by 17O NMR imaging. PMID- 1898416 TI - Comparison between alpha-adrenergic- and K-opioidergic-mediated inositol (1,4,5)P3/inositol (1,3,4,5) P4 formation in adult cultured rat ventricular cardiomyocytes. AB - In adult cultured rat ventricular cardiac myocytes, both the alpha-adrenergic agonist phenylephrine and the selective kappa opioid receptor ligand U-50, 488H affected phosphoinositide turnover. Phenylephrine, over a time course of 10 min, caused a transient increase in Ins(1,4,5)P3 which peaked at 1 min and had returned to control at 2 min. In addition, phenylephrine produced a progressive and sustained increase in the formation of Ins (1,3,4,5)P4 which achieved a plateau after 5 min of exposure to the agonist. U-50,488H induced an increase in Ins(1,4,5)P3 which peaked at 1 min at a level significantly higher than that due to phenylephrine and was still elevated after 10 min exposure to the kappa opioid receptor agonist. In addition, U-50,488H caused a sustained increase in Ins(1,3,4,5)P4 which was comparable to that due to phenylephrine. The stimulatory effects produced by phenylephrine and U-50,488H were receptor-mediated events, since they were fully antagonized by their respective antagonists, phentolamine or Mr-1452. PMID- 1898417 TI - Mitochondrial uptake of bridged bis-methylpyridinium aldoximes and induction of the "petite" phenotype in yeast. AB - The 3,3'-[omega,omega'-alkanediylbis(oxy)]bis[2- (hydroxyimino)methyl]-1 methylpyridinium derivatives bearing a linking chain of 4, 5 and 6 methylene groups are accumulated in mitochondria with increasing efficiency under the effect of the electrical potential. Accumulation does not take place with derivatives carrying a 2 and 3 methylene-long linking chain. The uptake process is saturable. The efficiency of the various derivatives to induce the "petite" phenotype in yeast reflects the uptake rate observed with purified mitochondria. PMID- 1898418 TI - Autoradiographic localization of 125I-big endothelin-1 in rat tissues. AB - Endothelin-1 (ET-1), a potent vasoconstrictor with a characteristically long acting activity in vitro and in vivo, is thought to be generated in endothelial cells from a less active intermediate, big endothelin-1 (big ET-1). In addition to ET-1, big ET-1 is also present in the circulation. The autoradiographic localization of 125I-big ET-1 has been studied after intravenous administration in rat tissues. Highest enrichment of radioactivity was found in the kidney cortex. Compared to blood levels, enrichment of radioactivity is also detected, especially in the vascular wall of the aorta. Comparing the radioactivity pattern of ET-1 and big ET-1, a nearly identical tissue distribution is observed, with the exception of the relative enrichment in the lung, the endocardium and the zona glomerulosa. PMID- 1898419 TI - Vasoactive properties of procyanidins from Hypericum perforatum L. in isolated porcine coronary arteries. AB - Procanidin fractions (PC) were isolated from Hypericum perforatum L. (Guttiferae). Characterization of the main components of each fraction was performed by UV- and mass spectroscopy. Their biological activity was tested in porcine isolated coronary arteries. All PC fractions antagonized histamine- or prostaglandin F2 alpha-induced arterial contractions. In contrast, vasorelaxation was insignificant in KCl-precontracted coronary arteries except with the higher oligomeric PC fraction 3. Vasoactive properties of the PC seem to be dependent on their relative molecular mass. An inhibition of cellular phosphodiesterase might be involved in the underlying mechanism of action. PMID- 1898420 TI - [Animal experimental and human pharmacologic studies with phase-II metabolites of triamterene]. AB - Animal Experiments and Human Studies with the Phase-II Metabolite of Triamterene The described animal experiments as well as the pharmacological investigations in man show the diuretic efficacy of the phase-II metabolite of triamterene (CAS 396 01-0), OH-TA-ester. As demonstrated in the present investigation, a phase-II metabolite can not be considered only as an ineffective conjugation product, formed to accomplish the excretion of a foreign compound, but also it must be considered as an important factor in the therapy, if its pharmacologic efficacy has been established, moreover if as a result of disease-related alterations in the pharmacokinetics the phase-II metabolite cumulates. PMID- 1898421 TI - In vitro antiplatelet profiles of the new thromboxane synthetase inhibitor sodium 2-(1-imidazolylmethyl)-4,5-dihydrobenzo[b]thiophene-6-carboxylate. AB - The in vitro properties of CS-518 (RS-5186; sodium 2-(1-imidazolylmethyl)- 4,5 dihydrobenzo[b]thiophene-6-carboxylate, CAS 113817-57-5), a new thromboxane (TX) synthetase inhibitor, as an antiplatelet agent were investigated. Incubation of clotting whole blood from man, rabbits, and dogs with CS-518 resulted in a concentration-dependent reduction of TXB2 production and an increase in 6-keto PGF1 alpha. Similar properties were also observed for ozagrel and isbogrel, but both agents were less effective on TXB2 production. CS-518 inhibited arachidonic acid (AA)- or collagen-induced platelet aggregation in platelet rich plasma (PRP) from man, rabbits and dogs. In addition, antiaggregatory effects of CS-518 were confirmed in whole blood by two methods: impedance method and free platelet count method. TXA2 formation in washed canine platelets in response to AA (0.1 mmol/l) was dose-dependently inhibited by incubation with CS-518. This inhibition by CS 518 was gradually attenuated after platelets were subsequently washed with drug free buffer, but a dose-dependent inhibition was still observed with platelets that had been washed three times. Ozagrel also inhibited TXB2 formation when incubated with platelets, whereas this inhibition disappeared with platelets only washed once. In contrast, platelets treated with acetylsalicylic acid, an irreversible inhibitor of cyclooxygenase showed a comparable inhibition before and after they were washed three times. These results indicate that CS-518 exerts antiplatelet effects in vitro via potent, selective, and long-lasting but reversible inhibition on TX synthetase. PMID- 1898422 TI - Substituted quinazolones as potent anticonvulsants and enzyme inhibitors. AB - A series of 6,8-disubstituted 3-[5- [[2-hydroxy-3-[(substituted phenyl)amino]propyl]thio]-1,3,4-thiadizol-2-yl] 2-methyl-4(3)- quinazolinones were synthesized whose structures were confirmed by elemental analyses, IR, NMR and mass spectral studies. All these compounds were evaluated in vivo for anticonvulsant and analgesic activities and in vitro for monoamine oxidase and succinate dehydrogenase enzyme inhibitory activities using rat brain homogenate as a source of enzyme at final concentration of 1 x 10(-4) mol/l. ALD50 values indicated their relatively nontoxic nature. PMID- 1898423 TI - [Ultrafiltration as a fast and simple method for determination of free and protein bound prilocaine concentration. Clinical study following high-dose plexus anesthesia]. AB - Ultrafiltration as a Fast and Simple Method to Separate Free and Protein Bound Concentrations of Local Anesthetics/Pharmacokinetic studies following high-dose anesthesia of the axillary plexus. As many other drugs amide-type local anesthetics are protein bound in plasma. The extent of binding varies between local anesthetics. The free, non protein-bound fraction of these drugs is mainly responsible for cardiovascular and central-nervous side effects. If high doses are necessary for regional anesthetic procedures it seems reasonable to determine the pharmacological active, non protein-bound fraction in addition to the total concentration of the local anesthetic drug. Analyses of protein binding was performed using an ultrafiltration method which is discussed in this paper. Total (HPLC) and unbound plasma levels (combination of ultrafiltration and HPLC) of the local anesthetic drug in central venous blood were studied in 20 healthy orthopedic patients, undergoing plastic surgery of the upper limb (elbow, forearm, hand), over a time period of 90 min, when performing axillary plexus block with 30 ml prilocaine (CAS 721-50-6) 2% (= 600 mg). Separation of the local anesthetic fractions was achieved using the ultrafiltration system MPS-1, equipped with a YMT-membrane. These membranes have a narrow pore size retaining molecules larger than 30000 Dalton. Ultrafiltration was accomplished by subjecting 1.2 ml of plasma to centrifugation at 2000 x g for 60 min at 30 degrees C using a clinical centrifuge equipped with a 35 degree angle head rotor. The plasma samples were adjusted to physiological pH (7.40) with a sodium potassium-phosphate buffer. The tightness of the used membrane was controlled by a micromethod for protein estimation (sensitivity 10 micrograms/ml).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1898424 TI - Evaluation of bronchospasmolytic, antiallergic, anti-inflammatory, mucolytic and antitussive activities of decasilate in experimental models. AB - The bronchospasmolytic, antiallergic, anti-inflammatory, mucolytic and antitussive activities of 8-(2-phenylethyl)-1-oxa-diazaspiro[4,5]decan-2-one 2 tiophenecarboxylate (decasilate, CAS 76652-72-7) have been evaluated using different experimental models. 1. Decasilate showed a remarkable spasmolytic activity against histamine-induced contractions in the isolated guinea-pig tracheal preparation with an IC50 of 2.7 x 10(-6) mol/l. In addition, the oral administration of decasilate (5-30 mg.kg-1) significantly reduced the histamine aerosol-induced bronchospasm in guinea-pigs. 2. Decasilate had a preventive effect against antigen-induced contractions of ileum segments from sensitized guinea-pigs (EC50 8.0 x 10(-6) mol/l) and relaxed them when added after the antigen challenge (IC50 9.5 x 10(-7) mol/l). 3. Both carrageenin- and dextran induced rat hind paw oedemas were significantly reduced by the oral administration of decasilate with ED50 values of 169.5 and 34.5 mg.kg-1, respectively. However, it was ineffective against the cotton pellet-induced granuloma in the rat. 4. Furthermore, decasilate had a significant mucolytic activity in rabbits and reduced the number of tussive seizures induced by an aerosol of citric acid in guinea-pigs. The pharmacological profile of decasilate suggests that it might be useful in the management of chronic bronchitis. PMID- 1898425 TI - Anti-inflammatory and immunomodulating effects of the novel agent gamma-(2 aminoethylamino)-2-butyrothienone. 2nd communication: inhibitory effect on rat adjuvant induced disease. AB - The effect of the novel agent gamma-(2-aminoethylamino)-2-butyrothienone (gamma ABT) on local and systemic changes of rats with adjuvant induced disease (AID) was investigated, gamma-ABT showed potent inhibitory effect on adjuvant primary inflammation and almost totally inhibited the secondary lesions. gamma-ABT improved the changes in lymphoid organ weight except of the thymus. gamma-ABT improved the change in albumin/globulin ratio, which is a parameter of systemic inflammatory reaction but did not improve the body weight gain in AID and normal rats. In addition gamma-ABT did not affect directly T or B lymphocytes as shown by the lymphocyte responses to mitogen (Con A) and a T cell dependent antigen (SRBC) but rather inhibited the suppressor cells found in AID. Although structurally gamma-ABT is completely different from known non-steroidal anti inflammatories, immunosuppressive drugs behave to a great extent like them. PMID- 1898426 TI - Antiarthritic effects of glucosamine sulfate studied in animal models. AB - The antireactive activity of glucosamine sulfate (GS) (CAS 29031-19-4) was tested in the rat in experimental models of subacute inflammation (sponge granuloma and croton oil granuloma), on subacute mechanical arthritis (kaolin arthritis) and in immunological-reactive arthritis and generalized inflammation (adjuvant arthritis). On these models GS was found effective in oral daily doses of 50-800 mg/kg. Tne potency of GS in comparison of that of indometacin used in the same tests as reference substance was found 50-300 times lower. Since, however, the toxicity of indometacin in chronic toxicity experiments is 1000-4000 times larger, the therapeutic margin with regard to prolonged treatments of inflammatory disorders results 10-30 times more favourable for GS than for indometacin. GS can therefore be considered as a drug of choice for prolonged oral treatment of rheumatic disorders. PMID- 1898427 TI - Effects of the new anti-ulcer agent 12-sulfodehydroabietic acid monosodium salt on healing of acetic acid-induced gastric ulcers in rats. AB - The macroscopic and microscopic effects of 12-sulfodehydroabietic acid monosodium salt (TA-2711, CAS 86408-72-2) on the healing of acetic acid-induced gastric ulcers in rats were compared with those of sucralfate and carbenoxolone. Test compounds were given orally twice a day for 10 consecutive days from the day after the injury with glacial acetic acid. TA-2711 (50 and 100 mg/kg) dose dependently decreased the macroscopic ulcer index (mm2). In addition, at a dose of 100 mg/kg, this drug decreased the length of mucosal defect in the ulcerated region and increased the mucosal regeneration index estimated by microscopic observation. Furthermore, the mucosa surrounding the ulcerated area and the regenerated epithelium in the TA-2711 administered group contained more PAS (periodic acid-Schiff)-positive material than those in the control group. On the other hand, neither sucralfate nor carbenoxolone (100 mg/kg) showed any significant effects on ulcer healing. PMID- 1898428 TI - Low frequency arterial wall movements for indirect blood pressure measurement in man. Validation of a method for non-invasive assessment of blood pressure under the influence of isoprenaline and angiotensin. AB - In order to measure blood pressure noninvasively, the second derivative of the low frequency wall movements of the brachial artery were registered with a piezo electric pressure probe during deflation of a Riva-Rocci cuff along with the actual cuff pressure. Two characteristic phenomena of this signal have been suggested to reflect systolic and diastolic blood pressure. Appearance of a positive spike phenomenon (S) was suggested to indicate systolic blood pressure and disappearance of a negative preanacrotic notch (D) to indicate diastolic blood pressure. To prove the validity of these suggestions, these phenomena were assessed in 10 young healthy males during isoprenaline and angiotensin induced changes of blood pressure. Intraarterial (A. radialis) and auscultatory (A. brachialis) blood pressures were recorded simultaneously. Determination of systolic blood pressure with the S phenomenon agreed well with invasive and auscultatory results. Invasive diastolic values agreed well with the cuff pressure at the last signal before disappearance of the preanacrotic notch (D1). Data from auscultation agreed less well with the D1 phenomenon. With increasing doses of isoprenaline, the diastolic measurements (D1) tended to be lower than the invasive ones. However, this discrepancy was far discreeter than that seen with ordinary auscultatory blood pressure measurement. We therefore conclude that registrations of low frequency arterial wall movements yield distinct characteristic spike phenomena useful for measurement of blood pressure in good agreement with the invasive method. In addition, the method provides clearly documented records and should be useful in situations which rely on a valid indirect method. PMID- 1898429 TI - Preparation of iodine labeled recombinant human erythropoietin. AB - 125I-labelled recombinant human erythropoietin (125I-rh-EPO; CAS for EPO: 11096 26-7) was prepared by using iodo-gen (1,3,4,6-tetrachloro-3,6-diphenylglycouril), which showed a similar immunoreactivity to anti rh-EPO anti-rabbit serum and a similar pharmacokinetics with that of non-labeled rh-EPO. PMID- 1898430 TI - Early identical twin studies. PMID- 1898431 TI - The effect of race on access and outcome in transplantation. PMID- 1898432 TI - Psychological damage of combat. PMID- 1898433 TI - Which anti-smoking programme? PMID- 1898435 TI - Affiliation between Hahnemann University and Pennsylvania College of Optometry. PMID- 1898434 TI - The effect of caffeine on postprandial hypotension in the elderly. AB - In a double-blind, randomized trial the effects of caffeinated and decaffeinated drinks on postprandial hemodynamic and neurohumoral changes were studied in seven fit, elderly subjects after a standard 2.4MJ meal. There was a significant difference in supine postprandial systolic blood pressure between the placebo and caffeine phases (P less than 0.01); at 60 minutes, supine systolic blood pressure had fallen 14 mmHg [95% confidence interval (CI)-7 to-21 mmHg, p less than 0.01) after placebo, but was unchanged after caffeine (+9 mmHg, CI 0 to 18 mmHg, NS]. Similar differences between placebo and caffeine were seen in erect systolic and diastolic blood pressure (P less than 0.01), although orthostatic tolerance was maintained throughout each study period. Postprandial plasma noradrenaline levels were higher (P less than 0.02) and the increase greater (P less than 0.02) after caffeine than after placebo. Caffeine administered at the end of a standard test meal prevents the postprandial fall in blood pressure in fit, elderly subjects. The clinical relevance of this finding has yet to be determined, but it may offer a simple remedy for patients with symptomatic postprandial hypotension. PMID- 1898436 TI - Patency rates for AK femoropopliteal bypass. PMID- 1898437 TI - More mercury from crematoria. PMID- 1898438 TI - Women, violent crime and the menstrual cycle: a review. PMID- 1898439 TI - Indirect costs. PMID- 1898440 TI - Cough. AB - Cough, although the most common respiratory symptom, is poorly understood by doctors. It is still widely believed that all cough occurs as part of mucociliary clearance and thus should only be inhibited with caution. However, it is now known that some and perhaps most cough occurs as a consequence of increased sensitivity of the cough reflex and therefore could be suppressed with safety. PMID- 1898441 TI - Mandating BSN for certification. PMID- 1898442 TI - Current practice of neonatal circumcision in the Waikato. AB - A survey of babies born in the Waikato revealed an incidence of neonatal circumcision of 7% in the first month. General practitioners performed 58% of these. About half were carried out before the baby left the maternity unit. Waikato maternity units had a wide variation in the rate of circumcision from 0 15%. Twenty percent of general practitioners offer neonatal circumcision as part of their services. Sixty-one percent of general practitioners said they try and dissuade parents from the practice. Also in replying to the questionnaire, of the 27 general practitioners who offered circumcision as part of their practice, six (22%) said they performed more than five circumcisions a year and 25% said they used a local anaesthetic. PMID- 1898443 TI - Cultural ethics and the autopsy. PMID- 1898444 TI - Duodenal ulcer: the villain unmasked? PMID- 1898445 TI - Alterations in brain high-energy phosphate and membrane phospholipid metabolism in first-episode, drug-naive schizophrenics. A pilot study of the dorsal prefrontal cortex by in vivo phosphorus 31 nuclear magnetic resonance spectroscopy. AB - In this pilot study, membrane phospholipid and high-energy phosphate metabolism were studied in the dorsal prefrontal cortex of 11 drug-naive, first-episode schizophrenic patients and compared with those of 10 healthy control volunteers comparable in age, education, and parental education. The schizophrenic patients had significantly reduced levels of phosphomonoesters and inorganic orthophosphate and significantly increased levels of phosphodiesters and adenosine triphosphate compared with the controls. The levels of phosphocreatine and adenosine diphosphate did not differ in the two subject groups. The adenosine triphosphate and inorganic orthophosphate findings suggest functional hypoactivity of the dorsal prefrontal cortex. The phosphomonoester and phosphodiester findings are compatible with either premature aging or an exaggeration of normal programmed regressive events occurring in the neural systems sampled. PMID- 1898446 TI - Electrophysiologic analysis of early Parkinson's disease. AB - We have been interested in the application of quantitative measures of motor performance as a possible means of early detection of Parkinson's disease. To assess motor function, we have measured movement time (the physiologic correlate of bradykinesia) and reaction time (simple and directional choice) with an upper limb motor task, and tremor with accelerometry and electromyographic recordings. In this report we describe preliminary data from a Parkinson's disease patient group with symptoms of fewer than 2 years' average duration (compared with an age and gender-matched normal control group) which indicate that precise, quantitative tests of motor function can detect the slight deviations from normal that are present in early Parkinson's disease. It appears that tests of bradykinesia are most sensitive, and detection of rest tremor is most specific. These tests may be applicable in screening individuals who are suspected of having or are "at risk for" Parkinson's disease and other related disorders. PMID- 1898447 TI - Lymphoepithelial cyst of the parotid gland. PMID- 1898448 TI - Increased initial lymphatic uptake in high-flow high-protein oedema: an additional safety factor against tissue oedema. PMID- 1898449 TI - Serum phospholipase A2 values and septic shock. PMID- 1898450 TI - The source of extra spleen colonies. PMID- 1898451 TI - Mood and motor fluctuations in Parkinson's disease. PMID- 1898452 TI - Pulmonary aspergillosis in AIDS. PMID- 1898453 TI - Hyperpyrexia, hemorrhagic shock and encephalopathy, and creatinine phosphokinase. PMID- 1898454 TI - Munchausen's syndrome simulating reflex sympathetic dystrophy. PMID- 1898455 TI - No firm basis to advocate auranofin in the treatment of juvenile rheumatoid arthritis. PMID- 1898456 TI - Coronary surgery without extracorporeal circulation. PMID- 1898457 TI - 'Laser success'. PMID- 1898458 TI - The politics of change. PMID- 1898459 TI - Postnatal depression and infant development. PMID- 1898460 TI - Preventing the spread of HIV infection. PMID- 1898461 TI - Cancer and HIV infection. PMID- 1898462 TI - Absence of risk associated with exposure to radiation before conception in Japan. PMID- 1898463 TI - Retinoids for cutaneous graft-versus-host disease, topical or systemic? PMID- 1898464 TI - Adolescent couple suicide. PMID- 1898465 TI - The impact of passive smoking; cancer deaths among nonsmoking women. PMID- 1898466 TI - The effect of amiodarone on the control of hyperthyroidism by propylthiouracil. PMID- 1898467 TI - Examining "licensing reexamined". PMID- 1898468 TI - Adenocarcinoma of the gallbladder. PMID- 1898469 TI - Dental anaesthesia and dementia. PMID- 1898470 TI - Selection of an artificial heart valve. PMID- 1898471 TI - Animal welfare. PMID- 1898472 TI - Visual acuity in patients with optic nerve pit. PMID- 1898473 TI - Topical corticosteroid-induced skin blanching measurement: eye or instrument? PMID- 1898474 TI - Surface electrode position during ulnar nerve stimulation. PMID- 1898475 TI - Guidelines for pharmaceutical company gifts. PMID- 1898476 TI - Lasers in dentistry. PMID- 1898477 TI - Scintigraphic assessment of thyroid cancer. PMID- 1898478 TI - Cognitive screening tests. PMID- 1898479 TI - There are the trees; the subject lesson of "NSAID gastropathy". PMID- 1898480 TI - Whole brain radiation. PMID- 1898481 TI - False positive tests for rubella-specific IgM. PMID- 1898482 TI - A stratified Wilcoxon-type test for trend. PMID- 1898483 TI - Intercostal arteriovenous fistula due to pleural biopsy. PMID- 1898485 TI - Paediatric scavenging system. PMID- 1898484 TI - Effect of fixatives and fixation times on tissues. PMID- 1898486 TI - Baccalaureate critical care nursing. PMID- 1898487 TI - PET reflections. PMID- 1898488 TI - Pneumatic dilation for achalasia: in- or outpatient? PMID- 1898489 TI - Smoking cessation and severity of weight gain. PMID- 1898490 TI - Parents' knowledge of children's suicide attempts. PMID- 1898491 TI - Normal smooth pursuit eye movements in volunteer subjects meeting schizotypal personality disorder criteria. PMID- 1898492 TI - Psychological effects of combat. PMID- 1898493 TI - Smokers of the future. AB - Teenagers continue to be initiated into smoking, especially young women. A predictor of smoking is the existence of stressors in their life. The major components of smoking motivation have been found to be similar in young smokers to those found in older smokers, except for the appearance of a group who are resisting the pressures against smoking. There is no evidence that the smokers of the future will be more extreme personality types than the smokers of 10 or more years ago. Changes in demographic characteristics of smokers in the United Kingdom and the United States in favour of relatively more women and more smokers from the poorer socio-economic groups requires investigation into whether this is attributable to different coping requirements in these groups. PMID- 1898494 TI - Stress and alcohol interaction: an update of human research. AB - The literature on alcohol and stress in human subjects carried out since 1981 is reviewed. The review covers selected aspects of the interaction of alcohol and stress. (1) Most of the review focuses on the role of stress on alcohol ingestion. Retrospective research based on data from the Health and Nutrition Examination Survey indicated an increase in alcohol consumption with anxiety in certain groups of, as yet not well characterized, individuals. For example, although still insufficiently documented, stress does not appear to play a significant role in alcohol ingestion by women and the elderly. By contrast, stress does appear to play a role in the control of alcohol ingestion by adolescents. Prospective studies employing questionnaire-interview formats generally support an effect of stress on alcohol ingestion. However, studies employing male college aged social drinkers did not find a correlation between levels of stress and ingestion of alcohol. Alcoholics also differ in the reasons for drinking alcohol, but generally ingest alcohol to lessen anxiety/stress. It is clear that the Tension Reduction Hypothesis as originally postulated is no longer adequate. Many new models based on an interaction of alcohol and stress have been proposed to explain the control of alcohol consumption. Considering the multidimensionality of factors that appear to contribute to the control of alcohol ingestion, it is unlikely that a single model could possibly be relevant to alcohol ingestion under all conditions. More likely different models may be relevant to alcohol consumption under specific conditions, or for specific populations. (2) Alcohol has been reported to decrease anxiety in agoraphobics. The self-medication by agoraphobics may contribute significantly to their alcohol abuse. (3) Alcohol has also been reported to decrease tremor of the hands in stressed subjects as well as in patients with essential tremor. (4) Although a number of studies have employed electrodermal activity in studies aimed at the interaction of alcohol and stress, the results have been rather inconsistent. (5) The controversy on the purported beneficial effect of alcohol on the cardiovascular system persists. A number of studies have shown a J- or U-shaped relationship between alcohol ingestion and incidence of coronary heart disease. Alcohol may also influence stress-induced changes in blood pressure. Although a number of studies have demonstrated lower blood pressure in individuals ingesting less than two drinks per day compared with abstainers or heavy alcohol imbibers, the evidence is not conclusive. (6) It is not clear whether the interaction of alcohol and stress involves alterations in plasma catecholamines.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1898495 TI - Effects of diabetes on cholinergic transmission in two rat gut preparations. AB - The gut may be a site of early diabetic neuropathy in humans and rats. The latter may provide appropriate models of these conditions. Therefore, cholinergic function was examined in two gut smooth muscle preparations from control, 30-day, and 6-month streptozotocin-diabetic and similarly diabetic rats that had received continuous treatment with an aldose reductase inhibitor, ponalrestat. Responses of terminal ileum longitudinal muscle to transmural nerve stimulation were depressed in preparations from untreated 30-day diabetic animals. Responses to exogenous acetylcholine were also depressed, by at least the same extent, in preparations from both 30-day and 6-month diabetic groups. Ponalrestat treatment prevented both changes in the 30-day study but did not prevent a depression of responses to acetylcholine in the 6-month study. Neither diabetes nor ponalrestat affected responses of esophageal muscularis mucosa to electrical stimulation or to exogenous acetylcholine. These observations suggest a change in the smooth muscle and/or noncholinergic innervation rather than in the cholinergic nerves of the ileal preparation. Cholinergic function in the ileum did not, therefore, seem to be an appropriate model of diabetic neuropathy. PMID- 1898496 TI - Segmental heterogeneity of cellular and paracellular calcium transport across the rat duodenum and jejunum. AB - Concentration- and voltage-dependent 45Ca transport was measured across the rat duodenum and jejunum. Mucosa-to-serosa calcium transport across the short circuited tissue exhibits a saturable component, whereas serosa-to-mucosa calcium flux in both segments is linear to the calcium concentration between 0.125 mmol/L and 10 mmol/L. Calcium is absorbed in the duodenum at concentrations between 0.125 mmol/L and 2.5 mmol/L but is secreted in the jejunum at all concentrations. The simultaneously measured paracellular marker [3H]mannitol at all calcium concentrations is secreted in both segments. The study across clamped preparations shows that (a) only mucosa-to-serosa calcium flux has a voltage independent cellular component; (b) serosa-to-mucosa calcium flux is totally voltage dependent, i.e., diffusive and probably restricted to the paracellular pathway; (c) diffusive calcium flux in the duodeum is equal in both directions; and (d) diffusive serosa-to-mucosa flux in the jejunum is higher than the corresponding flux in the opposite direction, suggesting that calcium passively is secreted in the jejunum as the consequence of a preference of the paracellular serosa-to-mucosa calcium movement caused by "anomalous solvent drag effect." 1 alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3] stimulates serosa-to-mucosa and more pronounced mucosa-to-serosa calcium flux and increases calcium absorption in the duodenum and abolishes calcium secretion in the jejunum. 1,25(OH)2D3 stimulates cellular mucosa-to-serosa calcium flux in the duodenum only but has no effect on cellular calcium in the jejunum. However, the vitamin increases bidirectional diffusive calcium fluxes across both segments. Tissue resistance is decreased and the flux of the paracellular marker mannitol in both directions is increased, suggesting that 1,25(OH)2D3 stimulates diffusive calcium flux across both segments by increasing the paracellular permeability. Dexamethasone inhibits cellular mucosa-to-serosa calcium flux and abolishes calcium absorption in the duodenum only but has no effect on cellular calcium flux in the jejunum. The glucosteroid has no influence on diffusive calcium flux in the duodenum but increases voltage-dependent bidirectional calcium flux across the jejunum. Simultaneously, the flux of the paracellular probe mannitol in both directions across the jejunum is increased, whereas mannitol flux in the duodenum is unresponsive to dexamethasone.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1898497 TI - Antroduodenal motility studied by real-time ultrasonography. Effect of enprostil. AB - Transabdominal real-time ultrasonography was used to investigate antroduodenal motility effects of the prostaglandin E2 analogue enprostil. Ten healthy subjects were studied on two separate days, once after oral administration of one capsule of enprostil 35 micrograms 1 hour before the ingestion of 500 mL of meat soup and once without drug administration before the meal. The ultrasound probe was positioned at the level of the transpyloric plane to visualize the antrum, pylorus, and proximal duodenum simultaneously and thereafter vertically to visualize the antrum, superior mesenteric vein, and aorta simultaneously. The motility was videotaped for 15 minutes. The antroduodenal coordination, frequency and amplitude of antral contractions, and size of antral area were reduced, whereas the time during which the pylorus was wide open (greater than 5 mm) was increased after enprostil. It is concluded that antroduodenal motility can easily be visualized by ultrasonography. Therapeutic doses of enprostil impair antroduodenal peristalsis and coordination and open the pylorus in healthy subjects. PMID- 1898498 TI - Biochemical and immunocytochemical characterization of mineral binding proteoglycans in rat bone. AB - We examined biochemically and immunocytochemically the type and distribution of mineral binding proteoglycans (PGs) in rat mid-shaft subperiosteal bone using three monoclonal antibodies (MAb 1-B-5, 9-A-2, and 3-B-3) which specifically recognize unsulfated chondroitin, chondroitin 4-sulfate (C4-S) and dermatan sulfate (DS), and chondroitin 6-sulfate. Bone proteins were extracted from fresh specimens with a three-step technique: 4 M guanidine HCl (GdnCl), aqueous EDTA without GdnCl (E-extract), followed by GdnCl. Western blot analysis of SDS polyacrylamide gel electrophoresis revealed that E-extract after chondroitinase ABC digestion reacted strongly with MAb 9-A-2 but not with MAb 1-B-5 or 3-B-3. After adehyde fixation, ethanolic trimethylammonium EDTA was used as a demineralizing agent for light and electron immunocytochemistry. This provided good retention of water-soluble PGs in the specimens. After chondroitinase ABC pre-treatment of tissue sections, MAb 9-A-2 specifically stained C4-S and/or DS in the walls of osteocyte lacunae and bone canaliculi in the mineralized matrix as well as in the unmineralized matrix such as pre-bone, vascular canals, and pericellular matrix surrounding osteocytes; the remainder of the mineralized matrix lacked staining. These results indicate that mineral binding PGs contain C4-S and/or DS and are exclusively localized in the walls of the bone lacuna and canaliculus. PMID- 1898499 TI - Ossification of posterior longitudinal ligament of the cervical spine in non Japanese Asians. AB - "The Japanese disease," ossification of the posterior longitudinal ligament, is not confined to the Japanese only. A similar incidence of 0.8% was found in this study among non-Japanese Asians. Of 5167 patients who attended the Mount Elizabeth Hospital in Singapore for cervical spine complaints, 43 patients were found to have ossification of the posterior longitudinal ligament, forming the largest non-Japanese series. All but one patient were of Mongolian origin, and males were affected four times more commonly than females. Diabetes mellitus was present in 16%. There was a significant association between ossification of the posterior longitudinal ligament and calcification of other cervical paraspinal ligaments. It is suggested that a generalized tendency to calcification may be an important etiological factor in ossification of the posterior longitudinal ligament. Four of the patients required surgery, and in our experience, anterior spinal fusion with removal of the ossified ligament or multilevel laminoplasty gives satisfactory results. PMID- 1898501 TI - Clinical decision analysis. PMID- 1898500 TI - Predictors of successful aging: a twelve-year study of Manitoba elderly. AB - In Manitoba, Canada, a representative cohort of elderly individuals ages 65 to 84 (n = 3,573) were interviewed in 1971 and the survivors of this cohort were reinterviewed in 1983. This analysis assesses the determinants of successful aging--whether or not an individual will live to an advanced age, continue to function well at home, and remain mentally alert. Over 100 separate indicators of demographic and socio-economic status, social supports, health and mental status in 1971 were available as potential predictors of successful aging. Indicators of access to health care over the period 1970-82 and indicators of diseases over this period were also available as predictors. Those who aged successfully were shown to have greater satisfaction with life in 1983 and to have made fewer demands on the health care system than those who aged less well. Despite the large number of potential predictors of successful aging which were examined, only age, four measures of health status, two measures of mental status, and not having one's spouse die or enter a nursing home were shown to be predictive of successful aging. PMID- 1898502 TI - Lasers 1990. PMID- 1898503 TI - Interaction of C-nitroso aromatics with polyunsaturated fatty acids: route to lipid peroxidation. AB - The possibility that the interaction of C-nitroso aromatics with polyunsaturated fatty acids (PUFA) causes lipid peroxidation was investigated through determination of conjugated diene and malodialdehyde (MDA) formation after anaerobic/aerobic vs. aerobic incubations of nitrosobenzene (NOB) or 2 nitrosofluorene (2-NOF) with linoleic, linolenic or arachidonic acid or methyl linolenate. Anaerobic incubation of NOB or 2-NOF with linolenic acid at the molar ratio of 1:1 for 24 h yielded approximately 5.5-13% of the PUFA as conjugated diene which appeared stable upon exposure to air. Interaction of PUFA and 2-NOF or NOB yielded MDA, the amounts of which were significantly greater when 24-h anaerobic preceded 1-6-h aerobic incubation. Furthermore, the differences in the amounts of MDA resulting from 24- and 0-h anaerobic incubations were significantly greater when the molar ratio of 2-NOF (or NOB) to PUFA was increased (2.0 greater than 1.0 greater than 0.5). Superoxide dismutase or catalase had no effect on the yields of MDA following either anaerobic/aerobic or aerobic incubations of PUFA and 2-NOF. EDTA (1 or 10 microM) had no effect on the yields of MDA from aerobic incubations, but it decreased the amounts of MDA (by approximately 30 or 60%, respectively) from anaerobic/aerobic incubations. The data suggested that inhibition by EDTA was due to chelation of trace iron, which following anaerobic interaction of PUFA and 2-NOF might have been reduced to Fe2+ and contributed to the enhanced lipid peroxidation. Thus, adduction of C-nitroso aromatics to PUFA yields radical species which directly and/or via reaction with trace iron lead to lipid peroxidation. The lipophilicity of C-nitroso aromatics suggests that this process may be of consequence in their mutagenesis/carcinogenesis. PMID- 1898504 TI - Selective induction of bilirubin UDP-glucuronosyl-transferase by perfluorodecanoic acid. AB - Differential effects of perfluorodecanoic acid (PFDA) on rat liver UDP glucuronosyltransferase isoenzymes have been observed after a single i.p. administration of the compound to young male Sprague-Dawley rats. (1) Bilirubin glucuronidation was induced 2-fold. The induced state was stable for at least 3 weeks. (2) Glucuronidation of 1-naphthol, morphine and testosterone was decreased to half of the control values. These decreases were maximal after 12 days but all three activities returned to normal levels after 3 weeks. (3) Immunoblotting experiments indicated that the differential effects of PFDA on UDP glucuronosyltransferase activities were due to modulation of enzyme protein concentrations rather than activation/inactivation mechanisms. With respect to its influence on UDP-glucuronosyltransferase isoenzymes, PFDA may be classified as a clofibrate-type inducer. The persistence of the induction after a single application however is unique among peroxisome proliferators and therefore PFDA may be a useful, elective inducer of bilirubin glucuronidation. PMID- 1898505 TI - Soluble immunologic products in scleroderma sera. AB - To investigate the role of immune mechanisms in scleroderma (systemic sclerosis, SSc), we measured the levels of selected cytokines and soluble immune markers in patient sera. Forty-two patients and 14 matched healthy controls are the subject of this report. In the SSc group, tumor necrosis factor (TNF) was found in 8/42 (29 +/- 539 pg/ml, mean level +/- SD) and lymphotoxin in 36/42 (1:409-1:200, serum dilution). Interleukin beta (IL-1 beta) was observed in 23/42 (44 +/- 29, U/ml). IL-2 was identified in 36/42 patients with a mean level of 286 +/- 406 U/ml, soluble interleukin-2 receptor in 42/42 (1055 +/- 393, U/ml), soluble CD4 antigen in 27/42 (1:10-1:320, serum dilution), and CD8 in 42/42 (470 +/- 134, U/ml). TNF, lymphotoxin, IL-1 beta, Il-2, and CD4 were not detected in the control group. IL-2 receptor levels in control subjects were 520 +/- 171 U/ml, significantly lower than those of scleroderma (P less than 0.001), and CD8 levels (582 +/- 140) were significantly higher than in scleroderma (P less than 0.05). The data suggest an ongoing activation of immune cells, particularly the CD4+ subset in SSc and indicate a potential role for the released mediator TNF, IL-1 beta, and lymphotoxin in the disease process. PMID- 1898506 TI - Ischemia of rat brain decreases pertussis toxin-catalyzed [32P]ADP ribosylation of GTP-binding proteins (Gi1 and G0) in membranes. AB - As an approach to understanding the molecular basis of the pathophysiology of cerebral ischemia, we examined qualitative and quantitative changes in pertussis toxin substrates, Gi1 and G0, in the membrane of rat cerebral cortex after decapitation. Within 1 min after decapitation, the extent of pertussis toxin catalyzed [32P]ADP ribosylation of the G proteins in the cerebral cortex membrane was significantly decreased and the magnitude of the decrease became slightly larger upon further incubation of the decapitated brain. Addition of guanine nucleotides, GTP and GDP, or the purified beta gamma subunits of transducin to the membranes of control and ischemic cerebral cortex stimulated [32P]ADP ribosylation of the G proteins. The stimulation of [32P]ADP ribosylation in the control situation by guanine nucleotides was almost to the same extent as that in ischemia. However, the stimulation by transducin beta gamma subunits was different; the control stimulation was greater than that in ischemia. In immunoblots probed with antibodies against Gi1 alpha, G0 alpha, and T beta, the immunoreactivity of the corresponding proteins in ischemia was similar to that in control, suggesting that the amounts of G proteins were not changed in ischemia. These results suggest that ischemia accelerates the dissociation of alpha-GDP beta gamma to alpha-GDP and free beta gamma and causes the denaturation of the dissociated alpha-GDP, thereby decreasing [32P]ADP ribosylation. PMID- 1898507 TI - Blood-tumor barrier disruption controversies. PMID- 1898508 TI - NSAIDs and bone metabolism. PMID- 1898509 TI - Pathologic assessment of bone. AB - Bone biopsy is an established diagnostic and investigative procedure that allows direct visualization of bone cells and structure and provides an indirect measure of bone turnover. It is widely used in management of metabolic bone disease and to explain any unclear biochemical abnormality affecting bone metabolism; it should become more widely used as its availability increases. Bone biopsy defines a variety of mineralization defects caused by fluoride, diphosphonates, and aluminum, and it provides unique insight into bone loss with age and with osteoporosis. It is necessary for evaluating rapidly progressive osteoporosis and it can be particularly useful for differentiating osteoporosis from osteomalacia. Although osteomalacia is often the result of decreased dietary vitamin D, there are recognized risk factors, such as previous gastric surgery or chronic renal disease. Nonetheless, clinical findings in osteomalacia are often rather subtle, and there may be few biochemical findings. Hence, if the patient is an elderly woman, and therefore also at risk for osteoporosis, the distinction can be difficult. Imaging studies are not likely to be helpful, since both disorders lead to decreased bone mass, usually at the same sites. The diagnostic criteria for osteomalacia are increased extent of osteoid surfaces, increased osteoid thickness, and thickened osteoid seams, in conjunction with a decreased calcification rate (as calculated by tetracycline labeling) and decreased calcification fronts. Osteoid volume alone is not an adequate diagnostic criterion, because it may also be increased in Paget's disease and hyperparathyroidism. Finally, biopsy is a valuable means to assess the effect of potential therapeutic agents on bone and bone cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1898510 TI - Assessing osteoporosis. PMID- 1898511 TI - Estrogen replacement therapy and osteoporosis. AB - Estrogen cannot replace bone that has been lost nor...straighten curvature of the spine or restore lost height. Usually, however, it can arrest the disease's progression. PMID- 1898512 TI - Stress fractures in the elderly. PMID- 1898513 TI - Mechanisms of fracture healing. AB - Bone is remarkable in that...it regenerates itself. In fact, it is the only tissue...except the liver with that regenerative capacity....The stages of healing in fracture callus recapitulate the spatial zones seen in the growth plate of a child. PMID- 1898514 TI - Rehabilitation of the fracture patient. AB - With any type of fracture it is important that rehabilitation begin when the fracture is stable, whether the stability occurred naturally or is achieved by internal fixation. PMID- 1898515 TI - New concepts in bone metabolism: clinical implications. AB - All of the common diseases of bone, as well as the bone changes seen with aging, are superimposed on the normal bone remodeling sequence.... In some common bone diseases, the balance between the processes of resorption and formation remains normal, but the rate of bone turnover is much higher. PMID- 1898516 TI - Clinical and financial outcomes in patient care in a home health care agency. PMID- 1898517 TI - Strain-specific enhancement of splenic T cell mitogenesis and macrophage phagocytosis following peripheral axotomy. AB - The inbred mouse strains C57BL/6 and DBA/2 were subjected to the selective depletion of peripheral nervous system norepinephrine (NE) by the administration of the neurotoxin 6-hydroxydopamine (6-OH-DA). Measurement of mitogen-induced lymphocyte proliferation following peripheral axotomy with 6-OH-DA revealed that significant enhancement (up to 200% of control values) of T, but not B, cell proliferative responses occurred in DBA/2, while no effect was observed in C57BL/6. Enhancement (up to 196% of control values) of luminol-enhanced chemiluminescence resulting from the phagocytosis of opsonized zymosan was also observed following 6-OH-DA treatment in DBA/2, but not C57BL/6. This strain specific enhancement of immune responses occurred even though the administration of 6-OH-DA resulted in a similar depletion of splenic NE content (greater than 97% reduction of control values) in both strains as determined by high-pressure liquid chromatography-electrochemical detection. Blockage of the neurotoxic effects of 6-OH-DA was achieved by the use of the catecholamine uptake blocker desipramine-HCl. Administration of desipramine prior to 6-OH-DA blocked the reduction of splenic NE content and abrogated the enhancement of mitogen-induced T cell proliferation. The enhancement of phagocytosis by 6-OH-DA was not, however, altered by the prior administration of desipramine. PMID- 1898518 TI - Tetraethylammonium, a K+ channel blocker, inhibits interferon-gamma-induced major histocompatibility class II antigen (Ia) expression and DNA synthesis in rat astrocytes. AB - Astrocytes play an important role in antigen presentation to T lymphocytes by their ability to express major histocompatibility class II (Ia) antigen upon exposure to a number of agents, including interferon-gamma (IFN-gamma). Astrocytes have been shown to express a variety of voltage-sensitive ion channels including voltage-sensitive K+ channels. The function(s) of these channels in astrocyte functions is not clearly understood. In this investigation, we examined: (1) the comparative effects of mouse, rat, and human recombinant IFN gamma (rIFN-gamma) on the induction of Ia antigen and DNA synthesis in rat astrocytes; (2) the effect of tetraethylammonium (TEA), a K+ channel blocker, on rat IFN-gamma-induced Ia expression and DNA synthesis in rat astrocytes. Our data show that all INF-gamma induce DNA synthesis in rat astrocytes but only rat and mouse and not the human IFN-gamma will induce Ia expression. TEA in a dose dependent manner inhibited both Ia expression and DNA synthesis in rat astrocytes. The concentration kinetics of TEA with regard to maximum inhibition of Ia and DNA synthesis were different. Furthermore, these inhibitory effects were not a result of toxic or nonspecific effect of TEA on astrocytes as demonstrated by viability data and lack of any effect of tetramethylammonium, an analogue of TEA, that does not block K+ ion channels. These data suggest a role of K+ channels in Ia expression and DNA synthesis, therefore in immunological functions of astrocytes. PMID- 1898519 TI - Differential appearance of extensively phosphorylated forms of the high molecular weight neurofilament protein in regions of mouse brain during postnatal development. AB - The appearance and accumulation of extensively phosphorylated forms of the high molecular weight neurofilament protein (H-phos) was studied in six regions of mouse brain during postnatal development by quantitative immunoblot analyses. H phos (migrating at 200 kDa) was detected in brainstem, cerebellum, cortex and hippocampus as early as postnatal day 1. While NF-H levels increased dramatically during subsequent postnatal development in these regions, and reached levels similar to those observed in adult brain by postnatal day 14, quantitative differences were observed in both the rate and the extent of increase among individual regions. The most rapid accumulation of H-phos was observed in brainstem and cortex, where H-phos increased within the first postnatal week to levels comparable to those of adult brain. However, H-phos exhibited a slower developmental change in cerebellum, where the levels increased uniformly over the first two postnatal weeks. In hippocampus, the major increase in H-phos levels was delayed until the second postnatal week. In contrast to its early detection in the above regions, H-phos was not detected in immunoblot analyses of olfactory bulb or hypothalamus cytoskeletons at postnatal day 1, indicating that in these regions the accumulated levels of posttranslationally modified forms of this protein appeared relatively late. Furthermore, H-phos levels in hippocampus did not level off at postnatal day 14 and continued to increase until at least postnatal day 21. Immunoblot analyses of whole embryonic brain revealed the presence of H-phos as early as embryonic day 17, demonstrating that some mouse brain regions carry out extensive phosphorylation of NF-H during embryonic development.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1898520 TI - Endoscopic injection of glutaraldehyde cross-linked bovine dermal collagen for correction of vesicoureteral reflux. AB - From November 1986 through May 1989, a Food and Drug Administration approved investigational study was done to assess the safety and efficacy of glutaraldehyde cross-linked bovine dermal collagen in the endoscopic treatment of vesicoureteral reflux. Over-all, 57 patients (92 ureters) were treated. The majority of ureters (68.5%) had grade II to III/V vesicoureteral reflux (international classification). One treatment was given in 61.4% of the patients, while 33.3% required 2 and 5.3% required 3 treatments. Nonduplicated/primarily refluxing ureters comprised 68.5% of the total, while 13% were duplex/primarily refluxing and 18.5% were surgical failures. The procedures were performed on an outpatient basis in all but 3 patients. Patients were evaluated by voiding cystourethrogram and renal/bladder sonography before and after treatment at 1 month and 1 year. Cure at 1 month after the last treatment was achieved in 75% of the ureters. Among the ureters cured at 1 month the cure persisted in 79% at 1 year after treatment. Cure at 1 year was achieved in 65% of all ureters evaluated, regardless of the status at 1 month. Procedure-related morbidity was minimal and there were no adverse reactions to the implant substance. Thus, glutaraldehyde cross-linked bovine dermal collagen appears to be safe and effective in the endoscopic treatment of vesicoureteral reflux. PMID- 1898521 TI - Cultured human bladder tumors for pharmacodynamic studies. AB - Human bladder tumor fragments were cultured on collagen gel. In this system, the three dimensional architecture, cell-to-stroma and cell-to-cell interactions, and tumor heterogeneity were maintained. Cell viability and labeling index (LI) were determined by exposure to 3H-thymidine and autoradiography. Of the samples from 20 patients with transitional cell carcinoma, 14 (70%) were successfully cultured and had a mean LI of 32%. In addition, one specimen from a patient with squamous cell carcinoma was cultured and had a LI of 61%. Cultured samples were tested for chemosensitivity using a two hour exposure of mitomycin C in concentrations ranging from one to 50 micrograms./ml. A dose-dependent relationship was demonstrated; LI decreased as mitomycin C concentrations increased. The methodology described provides an alternative to suspension or monolayer techniques of culturing human bladder tumors for pharmacological studies. PMID- 1898522 TI - Researchers express heartfelt wishes for success of molecular biology techniques in cardiac care. PMID- 1898524 TI - Nasal exhalation of cromolyn: a double effect. PMID- 1898523 TI - Intravenous thrombolysis and coronary revascularization rates. PMID- 1898525 TI - Deferral aims to deter Chagas' parasite. PMID- 1898526 TI - Clues and cure sought for HCV in Hispanics. PMID- 1898527 TI - Premarital sexual experience among adolescent women--United States, 1970-1988. AB - The initiation of sexual intercourse early in life is associated with an increased number of sex partners and a greater risk for sexually transmitted diseases (STDs). This report describes trends in age at first premarital sexual intercourse for adolescent women (15-19 years of age) in the United States during 1970-1988 and indicates an accelerated increase in the proportion having had premarital sex from 1986 to 1988. PMID- 1898528 TI - False-positive results with the use of chlamydia tests in the evaluation of suspected sexual abuse--Ohio, 1990. AB - On June 21, 1990, a commercial laboratory reported to a private residential-care facility for profoundly retarded persons in Ohio that rectal cultures from 10 residents tested positive for Chlamydia trachomatis. This report summarizes the epidemiologic and laboratory investigation by public health officials in Ohio and at CDC, which concluded that the C. trachomatis results were false-positive. PMID- 1898529 TI - Do the poor cost more? PMID- 1898530 TI - Exposure to dioxins and dibenzofurans through the consumption of fish. AB - BACKGROUND: In some regions, including the Baltic Sea, fatty fish such as salmon and herring contain high levels of polychlorinated dibenzodioxins and dibenzofurans. We investigated human exposure to these potentially toxic substances in relation to the consumption of fish from the Baltic Sea. METHODS: Plasma levels of 10 different dibenzofurans and 7 dioxins were analyzed in three groups of Swedish men: one group with a high intake of fish (fish eaten almost daily; n = 11), one with a moderate intake of fish (about once per week; n = 9), and one with no consumption of fish (usually because of allergy; n = 9). RESULTS: Plasma levels of several of the compounds we measured were higher in the men with a high intake of fish than in those who consumed moderate amounts, and the levels were higher in those who ate moderate amounts of fish than in those who ate none. The median amounts of the most toxic dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin) were 8.0 pg per gram of plasma lipid (range, 2.0 to 13) in the high-intake group, 2.6 pg per gram (range, 1.2 to 4.2) in the moderate-intake group, and 1.8 pg per gram (range, 1.0 to 2.5) in the nonconsumers (P = 0.001 and 0.02, respectively). There were consistent and statistically significant associations between the reported amount of fish eaten and the plasma levels of several of the dibenzofurans and dioxins. CONCLUSIONS: Contaminated fish such as those from the Baltic Sea are an important source of exposure to polychlorinated dibenzofurans and dibenzodioxins in persons who eat fish regularly. However, the clinical consequences of such exposure remain uncertain. PMID- 1898531 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 2-1991. A 60-year-old woman with hypertension, seizures, and mild renal failure. PMID- 1898532 TI - Influence of pravastatin on hepatic metabolism of cholesterol. PMID- 1898533 TI - Efficacy and cost effectiveness of adjuvant chemotherapy in women with node negative breast cancer. A decision-analysis model. AB - BACKGROUND: In 1988 the National Cancer Institute issued a Clinical Alert that has been widely interpreted as recommending that all women with node-negative breast cancer receive adjuvant chemotherapy. Acceptance of this recommendation is controversial, since many women who would not have a recurrence would be treated. METHODS: Using a decision-analysis model, we studied the cost effectiveness of chemotherapy in cohorts of 45-year-old and 60-year-old women with node-negative breast cancer by calculating life expectancy as adjusted for quality of life. The analysis evaluated different scenarios of the benefit of therapy: improved disease-free survival for five years, with a lesser effect on overall survival (base line); a lifelong benefit from chemotherapy; and a benefit in disease-free survival with no change in overall survival by year 10. The base-line analysis assumed a 30 percent reduction in the relative risk of recurrence for five years after treatment. RESULTS: For the 45-year-old woman, the base-line analysis found an average lifetime benefit from chemotherapy of 5.1 quality-months at a cost of $15,400 per quality-year. The 60-year-old women gained 4.0 quality-months at a cost of $18,800 per quality-year. Under the more and less optimistic scenarios, the benefit of chemotherapy varied from 1.4 to 14.0 quality-months for both groups. CONCLUSIONS: Chemotherapy substantially increases the quality-adjusted life expectancy of an average woman at a cost comparable to that of other widely accepted therapies. This benefit decreases markedly if the changes in long-term survival are less than in disease-free survival. Given its uncertain duration, the benefit may be too small for many women to choose chemotherapy. Selective use of chemotherapy to maximize the benefit to individual patients may be possible with refinements in risk stratification and explicit assessment of the patients' risk preferences. PMID- 1898534 TI - Branched-chain amino acid-free parenteral nutrition in the treatment of acute metabolic decompensation in patients with maple syrup urine disease. PMID- 1898535 TI - The effect of carbon dioxide laser surgery on the recurrence of keloids. AB - The efficacy of carbon dioxide laser excision as a primary modality for the treatment of keloids was evaluated. This retrospective study focuses on 31 patients with one or more keloids, 23 of whom were available for follow-up after carbon dioxide laser excision. The patients' ages ranged from 5 to 72 years. There were 16 females and 7 males. One patient was Caucasian, 22 patients were non-Caucasian, and there were no Asians. The keloids that were excised ranged in size from 1 to 30 cm in greatest diameter. One patient had no recurrence of her keloid after carbon dioxide laser excision, 9 patients required steroids to suppress recurrences, and 13 patients were considered failures. Reasons for the failure of this modality, as well as speculation regarding the future of this procedure, are discussed. PMID- 1898537 TI - Recombinant tissue-type plasminogen activator versus urokinase in peripheral arterial occlusions. PMID- 1898536 TI - Uveal melanoma: development of metastases after helium ion irradiation. AB - Forty-two (16%) of 261 patients with ocular melanoma who were treated with helium ions between January 1978 and November 1986 have developed metastatic disease. The time between start of helium ion treatment and recognition of metastatic disease ranged from 3 to 67 months (median, 27 months). The mean pretreatment tumor height in the patients with metastases was 7.7 mm. All 42 patients who developed metastatic disease have died. The median survival after diagnosis of metastatic disease was 5 months; the longest survival was 49 months. The most common site of metastasis was the liver (n = 34). Four (10%) of the 42 patients with metastases also had local recurrence of the tumor. Multivariate analysis identified three variables that predicted independently the development of metastases and lack of survival. These variables are anterior location of tumor (P = .027), tumor height greater than 5 mm (P = .02), and tumor diameter greater than 10 mm (P = .0075). PMID- 1898538 TI - Preclinical evaluation of MnDPDP: new paramagnetic hepatobiliary contrast agent for MR imaging. AB - Manganese(II)-N,N'-dipyridoxylethylenediamine-N,N'-diacetate-5,5'-bis (phosphate) (MnDPDP) is a paramagnetic complex designed for use as a hepatobiliary agent. The T1 relaxivity of MnDPDP (2.8 [mmol/L]-1.sec-1 in aqueous solution) was similar to that of gadolinium diethylenetriaminepentaacetic acid (DTPA) (4.5 [mmol/L]-1.sec 1) and gadolinium tetraazocyclodecanetetraacetic acid (DOTA) (3.8 [mmol/L]-1.sec 1). However, in liver tissue the T1 relaxivity of MnDPDP (21.7 [mmol/L]-1.sec-1) was threefold higher than that reported for Gd-DOTA (6.7 [mmol/L]-1.sec-1). Maximum liver T1 relaxation enhancement occurred 30 minutes after injection of MnDPDP, at which time 54MnDPDP biodistribution studies indicated that 13% of total body activity was in the liver. Enhanced (MnDPDP, 50 mumol/kg) MR images showed a fivefold increase in tumor-liver contrast-to-noise ratio over baseline unenhanced images. Results of the authors' acute and subchronic toxicity studies suggest that MnDPDP will be safe at the doses necessary for clinical imaging; at 10 mumol/kg, the safety factor (LD50/effective dose) for MnDPDP is 540, significantly greater than the safety factor of Gd-DTPA (ie, 60-100). PMID- 1898539 TI - Hepatobiliary MR imaging: first human experience with MnDPDP. AB - The first human MR imaging results for the hepatobiliary contrast agent manganese(II)N,N'-dipyridoxylethylenediamine-N,N'-diacetate 5,5'-bis(phosphate) (MnDPDP) are reported. MnDPDP is a paramagnetic contrast agent specific for hepatobiliary imaging. An imaging study was performed to investigate the presence of contrast enhancement or facilitated visualization of normal structures. Twelve healthy subjects receiving MnDPDP at doses of 3, 10, or 15 mumol/kg were imaged after injection for approximately 30 minutes at 1-5-minute intervals. Transaxial abdominal images were obtained at 1.5 T in a single breath-hold interval of 21 seconds with use of a spin-echo pulse sequence (repetition time = 150 msec, echo time = 20 msec). Liver parenchyma enhancement was observed 1 minute after injection and persisted for at least 30 minutes. Clearance into the gallbladder was visualized within 15 minutes. Enhancement was dose-dependent; a dose of 10 mumol/kg produced a 75%-100% signal enhancement of the liver at 10 minutes after injection. PMID- 1898540 TI - Barium enemas, latex balloons, and anaphylactic reactions. PMID- 1898541 TI - 1990 ARRS Executive Council Award. Renal transplant rejection: diagnosis with 31P MR spectroscopy. AB - We evaluated the role of 31P MR spectroscopy in the diagnosis of renal transplant allograft dysfunction. Thirty-six 31P MR spectroscopy examinations were prospectively performed in 35 patients with renal allografts. The study was performed in two phases. In the first phase, 12 transplant recipients with normal graft function were studied as normal controls. During phase two, 24 31P MR spectroscopy studies were performed in patients at the time of renal transplant biopsy for allograft dysfunction. Twenty-one of these studies were technically adequate. Pathologic analysis of the biopsy specimens showed evidence of allograft rejection in 14 and no rejection in seven. Various phosphorus metabolite ratios were calculated for each patient, including phosphodiesters/phosphomonoesters (PDE/PME), phosphomonoesters/inorganic phosphate (PME/Pi), and inorganic phosphate/adenosine triphosphate (Pi/ATP). The PDE/PME and Pi/ATP ratios in the allografts with rejection differed significantly from the corresponding metabolite ratios in patients without rejection (p = .017 and p = .024, respectively). A PDE/PME ratio exceeding 0.8 had a sensitivity of 100% and specificity of 86% for predicting rejection. A Pi/ATP ratio greater than 0.6 had a sensitivity of 72% and a specificity of 86% for predicting rejection. We conclude that 31P MR spectroscopy may be useful as a noninvasive method for evaluating renal metabolism during episodes of transplant allograft dysfunction. PMID- 1898542 TI - Failure of MR imaging to detect reflex sympathetic dystrophy of the extremities. AB - Reflex sympathetic dystrophy of the extremities is a disease with a wide spectrum of clinical manifestations. It is characterized by pain, hyperthermia, and cutaneous changes and has been linked to an abnormality of regional blood flow. The disease is associated with previous injury or trauma including surgery, but also has been found in association with myocardial infarctions and tumors. The final diagnosis can be made only on the basis of the clinical course, which is characterized either by regression without sequel or the appearance of aponeurotic and tendinous retractions including bony sclerosis in the affected region occurring over many months to years. The literature and our own results show that MR imaging has high sensitivity for diagnosing transient osteoporosis of the hip, which is generally thought to be a form of reflex sympathetic dystrophy. Therefore we investigated the usefulness of MR imaging for diagnosing sympathetic dystrophy of the extremities. Twenty-five patients underwent T1- and T2-weighted MR imaging of the affected body region. They were selected on the basis of the initial clinical findings and positive findings on scintigraphy, which is known to be a sensitive, but not very specific, imaging method for sympathetic dystrophy. The final diagnosis was established on the basis of the clinical course in 17 of the 25 patients. In 10 of these, findings on MR images were completely normal, in six the MR images showed only nonspecific soft-tissue changes or bone marrow sclerosis, and in one patient they showed changes in bone marrow signal. Of the remaining eight patients without a final diagnosis of sympathetic dystrophy, MR showed soft-tissue or bone marrow alterations in six. MR imaging appears to be of little value in establishing the diagnosis of sympathetic dystrophy, but it may improve diagnostic specificity when used in conjunction with scintigraphy. PMID- 1898543 TI - Sagittal MR images of the knee: a low-signal band parallel to the posterior cruciate ligament caused by a displaced bucket-handle tear. AB - A low-signal band parallel and anterior to the posterior cruciate ligament has been noted on sagittal MR images of the knee in some patients with other evidence for medial meniscal tears. It was hypothesized that this low-signal band represented the mesially displaced fragment of a bucket-handle tear. To verify this, we retrospectively reviewed MR and arthroscopic findings in 54 consecutive patients. Arthroscopy showed a bucket-handle tear of the medial meniscus in seven patients and was considered diagnostic. Sagittal MR images were reviewed without knowledge of the arthroscopic results. The presence of a curvilinear low-signal band above the tibial cortex anterior, inferior, and parallel to the posterior cruciate ligament was identified on MR images in all seven of the patients in whom the presence of a bucket-handle medial meniscal tear was confirmed by arthroscopy. Our findings suggest that a low-signal band anterior and parallel to the posterior cruciate ligament on sagittal MR images of the knee is caused by a mesially displaced bucket-handle tear of the medial meniscus. PMID- 1898544 TI - MR imaging of displaced bucket-handle tear of the medial meniscus. AB - A bucket-handle tear of the meniscus is a vertical or oblique tear with longitudinal extension toward the anterior horn in which the inner fragment is frequently displaced toward the intercondylar notch with resultant mechanical locking of the knee joint. A precise MR diagnosis requires identification of the centrally displaced fragment because the peripheral nondisplaced component may have only a subtle truncated or foreshortened appearance that may escape detection. Eighteen consecutive cases of displaced bucket-handle tears of the medial meniscus diagnosed by MR had a characteristic low-signal band extending across the joint and projecting over the medial tibial eminence. The posterior portion was parallel and beneath the posterior cruciate ligament on both sagittal and coronal images. Arthroscopy confirmed the presence and location of the displaced fragment in all 18 cases. Awareness of this characteristic MR finding may increase the sensitivity of MR imaging in the diagnosis of bucket-handle tears of the medial meniscus. PMID- 1898545 TI - Rheumatoid arthritis of the knee: value of gadopentetate dimeglumine-enhanced MR imaging. AB - In an attempt to differentiate among joint effusion, synovitis, pannus, and subchondral sclerosis in patients with clinically proved chronic rheumatoid arthritis, we used gadopentetate dimeglumine-enhanced MR imaging to examine 23 patients with acute knee symptoms. All patients had had rheumatoid arthritis for more than 6 months and satisfied four or more of the criteria of the American Rheumatism Association for rheumatoid arthritis. MR imaging was performed on a 1.5-T machine by using unenhanced T1-weighted spin-echo imaging, unenhanced T2* weighted gradient-echo imaging, and unenhanced and enhanced T1-weighted gradient echo imaging. Signal intensities of the synovium and bone marrow were measured with the region-of-interest technique on unenhanced and enhanced T1-weighted gradient-echo scans. Conventional radiographs were available for each patient. Joint effusion, synovitis, intraarticular pannus, subchondral sclerosis, and subchondral pannus had the same signal intensities on unenhanced T1-weighted spin echo, unenhanced T1-weighted gradient-echo, and unenhanced T2*-weighted gradient echo MR images, and could not be differentiated from one another. On enhanced T1 weighted gradient-echo sequences, pannus and synovitis showed marked enhancement in 15 patients, whereas joint effusion and sclerosis did not. Synovitis was diagnosed if the synovial membrane showed high enhancement; pannus was diagnosed if enhancing masses were seen within the joint space or in the subchondral area. In eight of the 23 joints, there was no enhancement of the synovium or intraarticular or subchondral tissue. We conclude that gadopentetate dimeglumine enhanced MR imaging allows differentiation between synovitis and joint effusion and between subchondral pannus and subchondral sclerosis. Enhancement of the synovium and pannus indicates acute inflammation of the joint. PMID- 1898546 TI - MR imaging of the lateral collateral ligament of the ankle. AB - The ankle is stabilized by three sets of ligaments: the medial collateral (deltoid) ligament, the syndesmotic ligamentous complex, and the lateral collateral ligament. Of these three, the lateral collateral ligament is the one most often injured in ankle sprains. Assessment of the extent of injury has classically relied on clinical evaluation; plain film radiographs (including stress views); and, in some acute situations, ankle arthrography and/or peroneal tenography. In this report we illustrate the use of MR in the evaluation of the lateral collateral ligament. The normal anatomy, pitfalls in image interpretation, and findings in cases of ligamentous injury are demonstrated. PMID- 1898547 TI - Urethral abnormalities in male neonates with VATER association. AB - In the past 3 years, eight of 20 male neonates with stigmata of the VATER association were found to have significant urethral abnormalities. Three had megalourethra, two had duplication of the urethra, and one each had an anterior urethral valve, congenital stricture, and hypospadias. In only five of eight was the extent of the abnormality clinically apparent. All three infants with megalourethra and imperforate anus died because of the coexistence of other severe congenital anomalies. Prior literature has described but not stressed the increased prevalence of urethral abnormalities in children with the VATER association. Because of the high prevalence (eight of 20) of significant urethral anomalies, we perform voiding cystourethrography on all males with the stigmata of the VATER association, even in the absence of clinical symptoms. PMID- 1898548 TI - Sonography in neonatal congenital adrenal hyperplasia. AB - Adrenal gland size was evaluated in six infants with congenital adrenal hyperplasia. All of the infants had a severe deficiency of the 21-hydroxylase enzyme resulting in the salt-losing form of congenital adrenal hyperplasia. The adrenal measurements were compared with those of 40 consecutive age-matched, asymptomatic infants. Mean adrenal length was 14.4 mm and width was 1.9 mm in asymptomatic infants, whereas in infants with congenital adrenal hyperplasia mean adrenal length was 23.7 mm and width was 5.3 mm. Although infants with congenital adrenal hyperplasia may have normal-sized adrenal glands, mean length measurements of 20 mm or greater and mean width measurements of 4 mm or greater suggest the diagnosis. PMID- 1898549 TI - Mediastinal pseudomass caused by compression of the thymus in neonates with anterior pneumothorax. AB - We studied the radiographs of 115 neonates with anterior pneumothoraces to determine how often the pneumothorax created the impression of a mediastinal pseudomass. The pseudomass results from compression of the thymus gland by air under pressure. To the unwary, the resulting configuration can lead to an erroneous diagnosis of a mediastinal mass. In experienced hands, however, it can serve as a strong clue to the presence of an underlying anterior pneumothorax. A pseudomass was present in 27 (33%) of 82 neonates with unilateral pneumothoraces and in 29 (88%) of the 33 patients with bilateral anterior pneumothoraces. A free lung edge was visualized in 26% of the patients with a unilateral pseudomass and in 55% of the neonates with a bilateral pseudomass. The pseudomass was large enough to potentially lead to a misdiagnosis in one third of the cases. In the other neonates the mass was smaller and not particularly problematic. The majority of the neonates with pseudomasses were large, not intubated, and not on positive-pressure assisted ventilation. Over half had no underlying pulmonary disease. The appearance of a mediastinal pseudomass on radiographs of neonates can obscure a pneumothorax, and lead to an erroneous diagnosis. Recognition of the pseudomass as a manifestation of pneumothoraces is important. PMID- 1898550 TI - Normal sonographic appearance of a thanatophoric dwarf variant fetus at 13 weeks gestation. PMID- 1898551 TI - The evaluation of coronary bypass graft patency: direct and indirect techniques other than coronary arteriography. AB - Patients having one or more coronary artery bypass graft operations constitute an important part of the practice of cardiac radiology. Bypass graft patency can be determined by indirect and direct methods. The indirect imaging methods include radionuclide ventriculography, thallium-201 scintigraphy, and positron emission tomography. The direct methods include conventional CT, ultrafast CT, MR imaging, digital subtraction angiography, and Doppler sonography. This review discusses the advantages and limitations of these methods and attempts to define the relative importance of each of these techniques in the evaluation of bypass graft patency. PMID- 1898552 TI - CT of acute splenic torsion in children with wandering spleen. PMID- 1898553 TI - Focal high signal on MR scans of the midbrain caused by enlarged perivascular spaces: MR-pathologic correlation. AB - Punctate and linear foci of abnormal signal were observed near the substantia nigra in the midbrains of 32 (20%) of 157 patients undergoing high-resolution MR imaging of the brainstem. The lesions were most easily seen on long TR/long TE images, where they were of high signal intensity. Their location was consistently in the lower mesencephalon near the junction of the substantia nigra and cerebral peduncle. Unilateral lesions were observed in 18 cases, while bilateral lesions were noted in 14. A review of anatomic specimens revealed the constant presence of penetrating branches of the collicular or accessory collicular arteries in this location. Enlarged perivascular spaces around these vessels were frequently seen in the specimens and probably account for punctate and linear foci observed on high-resolution MR images of the midbrain. PMID- 1898554 TI - Normal venous anatomy of the brain: demonstration with gadopentetate dimeglumine in enhanced 3-D MR angiography. AB - This investigation evaluates whether gadopentetate dimeglumine enhancement of three-dimensional (3-D) acquisition MR angiography can generate clinically useful images of the normal venous anatomy of the brain. 3-D MR angiography of normal cerebral arterial anatomy has made rapid progress, although demonstration of detailed venous anatomy with similar techniques has been much less revealing. To overcome the limitation of slow venous flow, IV gadopentetate dimeglumine contrast enhancement was used to alter the relaxation times of blood, thus augmenting the venous signal. Several groups of patients were evaluated: we studied eight patients both with and without contrast enhancement, 20 patients and volunteers with multiple techniques to determine optimal technical parameters, and seven patients in whom enhanced MR studies were compared with standard selective biplane cut-film arterial angiograms. Only the large dural sinuses (such as the transverse sinus) could be seen on unenhanced studies owing to the saturation of slowly flowing venous spins. With contrast enhancement, many of the important small and large cerebral venous structures were routinely seen with reasonable scanning times (7 min). The venous anatomy was well seen for approximately one-half hour after injection and correlated well with angiograms. There are several important limitations to this technique, including a limited field of view, variable visibility of specific veins owing to technical and physiologic factors, confusion of enhancing non-flow-related structures, and lack of detailed physiologic information. Single excitation 3-D MR angiograms are insensitive in the evaluation of cerebral venous structures. Enhancement with gadopentetate dimeglumine affords rapid scanning and excellent visualization of the pertinent venous anatomy. The best image quality was obtained with a sequence of 50/7/30 degrees (TR/TE/flip angle). PMID- 1898555 TI - Atherectomy facilitated by long vascular sheaths. PMID- 1898557 TI - Hypersensitivity reaction to oral iohexol. PMID- 1898556 TI - Analysis of the cost-effectiveness of PACS. AB - Picture archiving and communications systems (PACS) have emerged as an important part of digital imaging technology. However, the future of PACS is uncertain because its economic viability is in doubt. Cost-effectiveness analysis is an accepted technique for evaluating the economics of new technologies. This paper addresses the cost-effectiveness of PACS and identifies factors that are important in determining the cost of PACS relative to film-based radiology. These include the impact of PACS on physician productivity, maintenance costs, discount rates, and the time period for amortization of capital goods. The effectiveness of PACS is also explored in terms of improvements in diagnostic accuracy and timely diagnosis. Financial and clinical impacts should be integrated to provide information about how PACS expenditures will affect radiology departments, hospitals, and national research and development objectives. PMID- 1898558 TI - Clinical history and accurate interpretation of chest radiographs. PMID- 1898559 TI - Defining terms for medical decision making. PMID- 1898560 TI - Mucocele of the breast. PMID- 1898561 TI - Buckled meniscus revisited. PMID- 1898562 TI - CT of bilateral cervical spondylolysis. PMID- 1898563 TI - Childproof cap on medicine bottles as a risk for esophageal foreign body. PMID- 1898564 TI - Coarctation of the abdominal aorta associated with malignant hypertension and collateral mesenteric circulation. PMID- 1898565 TI - Intrasigmoidal aorta-bifurcation prosthesis diagnosed on CT. PMID- 1898566 TI - CT of the gastrointestinal tract: principles and interpretation. AB - The experience accumulated in daily abdominal CT scanning and CT evaluation of gastrointestinal lesions has generated helpful technical guidelines and some reliable principles of interpretation. These general principles are briefly discussed in this review, and the importance of performing a CT examination that is adequate for the detection and evaluation of gastrointestinal lesions is stressed. CT features useful in differentiating benign from malignant lesions, limitations and pitfalls in CT interpretation, overlap in the CT appearance, and classical CT features leading to specific diagnoses are described and illustrated. Although CT is established as one of the most important techniques for imaging the gastrointestinal tract, it should be used selectively and only in the context of appropriate clinical and conventional radiologic examination. CT should not be regarded as competing with, but as complementing, barium examination of the gastrointestinal tract. PMID- 1898567 TI - Color Doppler flow imaging. AB - The performance requirements and operational parameters of a color Doppler system are outlined. The ability of an operator to recognize normal and abnormal variations in physiologic flow and artifacts caused by noise and aliasing is emphasized. The use of color Doppler flow imaging is described for the vessels of the neck and extremities, upper abdomen and abdominal transplants, obstetrics and gynecology, dialysis fistulas, and testicular and penile flow imaging. PMID- 1898568 TI - Selective salpingography and fallopian tube recanalization. AB - Obstruction of the uterine (proximal) end of the fallopian tube is noted on up to 20% of hysterosalpingograms and has a variety of underlying causes. Definitive diagnosis and treatment in the past have required laparoscopy or laparotomy with tubal resection. Selective salpingography and fallopian tube recanalization with fluoroscopically guided catheters has emerged as an improved method both for diagnosis and treatment in these patients. Technical success rates for overcoming the obstruction and visualizing distal tubal anatomy range from 76% to 95%. Pregnancy rates after the procedure vary depending on the patient populations studied; however, early results indicate a greater than 50% intrauterine pregnancy rate by 1 year. The rate of ectopic pregnancy is approximately 10% and that of early tubal reocclusion is less than 30%. Selective salpingography and fallopian tube recanalization is recommended as the first intervention in patients with obstruction of the proximal fallopian tube. PMID- 1898569 TI - High-attenuation mediastinal masses on unenhanced CT. AB - On unenhanced CT scans, a variety of mediastinal masses contain areas with attenuation values higher than the attenuation value of the chest wall musculature. The increased attenuation may be diffuse or focal and may be a result of calcium deposition, high iodine content, or areas of acute hemorrhage. This report illustrates the gamut of high-attenuation mediastinal masses seen on unenhanced CT. Masses that are of high attenuation only on IV contrast-enhanced images (e.g., aberrant vessels) are not included. PMID- 1898570 TI - Diaphragmatic rupture due to blunt trauma: sensitivity of plain chest radiographs. AB - Preoperative diagnosis of diaphragmatic rupture caused by blunt injury is often difficult because of serious concurrent injuries, a lack of specific clinical signs, and simultaneous lung disease that may mask or mimic the diagnosis radiologically. Previous reports have suggested that a preoperative diagnosis is established on the basis of chest radiographs in only one third of patients. In order to assess the value of chest radiographs and other imaging techniques in diagnosing traumatic rupture of the diaphragm, we retrospectively reviewed all preoperative diagnostic imaging performed in 50 patients with surgically proved hemidiaphragmatic rupture due to blunt trauma. Chest radiographs were diagnostic in 20 (46%) of 44 patients with left-sided rupture and were considered suspicious enough to warrant further diagnostic studies in an additional eight patients (18%). Five patients with initially normal findings on chest radiographs had diagnostic findings on delayed chest radiographs. Chest radiographs were strongly suggestive in only one (17%) of six patients with right-sided hemidiaphragmatic rupture. CT was diagnostic for diaphragmatic rupture in only one (14%) of seven instances in which it was performed. MR was diagnostic in both patients in whom it was performed. Our experience indicates that chest radiographs obtained at admission and repeated soon after are more valuable in suggesting the diagnosis of traumatic rupture of the diaphragm than previously reported, particularly in the more frequent, left-sided injuries. This increased sensitivity may be due to a greater level of suspicion maintained in a trauma referral center in which this injury is not uncommon. PMID- 1898571 TI - Present status of residency training in mammography. AB - We conducted a telephone interview of all 207 accredited diagnostic radiology residency training programs listed in the American Medical Association's Directory of Graduate Medical Education Programs. Resident training in mammography was offered in 206 programs, and 35% of the programs had initiated this training within the past 3 years. Residents had an assigned block of time to do mammography in 84% of the programs. Of the 206 programs, 40% had rotations devoted exclusively to mammography, with 82% of the exclusive rotations lasting from 4 to 8 weeks. Residents were performing localization procedures in 91% of the programs and dictating cases in 81%. A distinction was made between screening and diagnostic examinations by 35% of the training institutions, at least in terms of the fee for the examination. Radiologists who devoted at least half of their practice to mammography taught in 52% of the programs. The American College of Radiology has granted accreditation in mammography to 29% of the programs. Although almost all accredited residency training programs offer training in mammography, there are some deficiencies in this training. More residents need to gain the experience of dictating mammography reports and need to learn about the distinctions between screening and diagnostic mammography. Despite the anticipated deluge of screening examinations in the next decade, there were only 17 fellowships that included at least 6 months of mammography identified in 15 (7%) of the institutions; only 11 of these were full-time 1-year breast imaging fellowships. PMID- 1898572 TI - Endoscopic sonography of the upper gastrointestinal tract. AB - Endoscopic sonography was used to examine the upper gastrointestinal tract of 550 patients referred for evaluation of abnormal findings seen on conventional endoscopy, upper gastrointestinal series, and CT. This essay illustrates the potential uses and limitations of this technique. Special emphasis has been given to the use of landmarks to facilitate orientation of the transducer in both the esophagus and stomach. Specific examples demonstrate involvement of individual layers of the bowel wall in both benign and malignant processes. It is stressed that this is a combined procedure requiring both an endoscopist and a radiologist. Endoscopic sonography is a valuable new technology with substantial potential in the evaluation of the upper gastrointestinal tract. PMID- 1898573 TI - Percutaneous transluminal biopsy of biliary strictures with a bioptome. PMID- 1898574 TI - Duplex Doppler sonography of the hepatic vein in tricuspid regurgitation. AB - Patients with tricuspid regurgitation may present initially with vague abdominal symptoms and elevated liver enzymes. In the absence of diagnostic sonographic findings, patients may be subjected to an unnecessary invasive liver biopsy for an accurate diagnosis. We recently described the association of the pulsatile portal venous waveform on duplex Doppler sonography with tricuspid regurgitation in 15 patients. In this study I describe the changes in the hepatic venous waveform in these patients and compare the findings with the final diagnosis as determined by Doppler echocardiography (n = 14) or ultrafast CT (n = 1). All patients had clinical findings consistent with liver dysfunction and were referred for sonography to rule out diseases of the liver, biliary tree, or hepatic or portal veins. All patients had persistently dilated hepatic veins and inferior venae cavae. Twenty-four volunteers, 11 of whom had simultaneous ECG tracings, served as a control group. The main findings on the hepatic duplex sonogram in the disease group were a decrease in the size of the antegrade systolic wave with a systolic/diastolic flow velocity ratio of less than 0.6 (n = 4) or reversal of the systolic wave (n = 10). In all volunteers, systolic flow was antegrade and the ratio was more than 0.6. Two diagnoses were false positive and one was false negative. In some patients with sonographic signs of congestive heart failure, duplex Doppler sonography of the hepatic vein may be helpful in the diagnosis of one of the causes of liver dysfunction, tricuspid regurgitation. PMID- 1898575 TI - Portal venous system after portosystemic shunts or endoscopic sclerotherapy: evaluation with Doppler sonography. AB - We sought to determine the usefulness of duplex Doppler sonography in the assessment of blood flow and clot formation in the portal vein in 44 patients with portal hypertension and bleeding esophageal varices who had undergone either endoscopic sclerotherapy (28 cases) or portosystemic shunt procedures (16 cases). The main, left, and right portal veins (collectively referred to as intrahepatic portal veins), superior mesenteric vein, splenic vein, and shunt were assessed for flow direction, presence of thrombi, and collaterals. Patent shunts were visualized in 12 (75%) of the 16 cases. Clot was detected in 27 (69%) of 39 intrahepatic portal veins in patients with end-to-side shunts, in six (67%) of nine intrahepatic portal veins in patients with distal splenorenal shunts, and in five (5%) of 92 intrahepatic portal veins in patients who had had endoscopic sclerotherapy. Flow in the main portal vein was hepatopetal in two (15%) of 13 patients with patent shunts (one end-to-side portacaval shunt and one distal splenorenal shunt). Flow in the main portal vein was hepatopetal in 26 (93%) of 28 patients who had had endoscopic sclerotherapy. Our data suggest endoscopic sclerotherapy preserves antegrade portal flow and results in fewer portal vein clots than surgical portosystemic shunts do. Patterns of thrombosis and flow direction vary unpredictably from patient to patient. Shunt patency should not be inferred without direct visualization of the shunt. PMID- 1898576 TI - CT of acute pancreatitis: correlation between lack of contrast enhancement and pancreatic necrosis. AB - This study was performed to determine if a correlation exists between pancreatic parenchymal enhancement or lack thereof on contrast-enhanced CT and surgical evidence of pancreatic necrosis. Accurate CT assessment of pancreatic vascular perfusion would be helpful in preoperative planning before pancreatic debridement and necrosectomy. The CT scans and medical records were blindly and retrospectively reviewed in 13 patients with the operative diagnosis of pancreatic necrosis. In all cases, CT examinations preceded surgery within 72 hr. Surgical and pathologic findings served as the gold standards for the diagnosis of pancreatic necrosis. Seven (54%) of 13 patients had a region or regions of parenchymal necrosis within the head, body, and/or tail of the pancreas seen during surgery. All seven of these patients had no pancreatic enhancement on CT in at least one region of the pancreas (CT sensitivity = 100%). In four of the seven, two regions were found to be necrotic at surgery, but only one of the two segments did not enhance on CT scans. In three of the seven patients, lack of contrast enhancement on CT (no enhancement of the pancreatic head and body in two patients and throughout the gland in another) correlated with necrosis in the same regions at surgery. The remaining six (46%) patients, who had peripancreatic or small, focal, and/or superficial areas of pancreatic necrosis at surgery, had normal pancreatic enhancement on CT. Our results show that regions of pancreatic necrosis found surgically correlate with lack of enhancement of pancreatic parenchyma on CT. Peripancreatic necrosis and minor areas of focal or superficial parenchymal necrosis were not detected on CT. PMID- 1898577 TI - Pancreatitis with pseudoaneurysm formation: a pitfall for the interventional radiologist. PMID- 1898578 TI - Endoluminal sonography of the urinary tract: preliminary observations. AB - Endoluminal sonography of the urinary tract was performed by using endoluminal ultrasound transducers contained within 2-mm-diameter catheters. The catheters were inserted into the urinary bladder via the urethra and advanced into the ureters and renal pelvis under cystoscopic control; then, cross-sectional images of the bladder, ureters, and renal pelvis were obtained. Two dogs and seven human patients were studied. In one dog, a 4.5-mm pseudopolyp, which was surgically created in the bladder wall, was successfully imaged; in the other, stones 2 mm or larger inserted into the bladder were identified. Of the seven patients, sonography showed stones embedded in the renal parenchyma (one patient) and the mucosa of the distal ureter (one patient). These were ultimately confirmed by their eventual removal. In a third, sonography showed a tumor of the distal ureter and identified the depth of the tumor. This was confirmed by biopsy. In a fourth, sonography clearly showed a crossing vessel as the cause for narrowing of the proximal ureter. In a fifth, sonography showed that the cause of a ureteral stricture was idiopathic. In the last two cases, sonography did not reveal a cause for hematuria. In these last three cases, negative sonographic results were confirmed by direct ureteroscopic examinations and follow-up studies. Our observations based on this limited study suggest that endoluminal sonography is a useful procedure for diagnosing diseases of the urinary tract. Further study is warranted. PMID- 1898579 TI - Enteral alimentation and repletion of body cell mass in malnourished patients with acquired immunodeficiency syndrome. AB - The aim of this study was to determine the feasibility, tolerance, and efficacy of enteral feeding in malnourished AIDS patients. This was a prospective study of eight AIDS patients with severe eating disorders associated with systemic diseases. A defined diet was administered through an endoscopically placed gastrostomy tube. Body composition studies and selected serum and immunologic studies were done at baseline and monthly for 2 mo. Enteral feeding was associated with an increase of approximately 14% in total body potassium, an index of body cell mass (P less than 0.02), and an increase in body fat content (P less than 0.002). Serum albumin concentration (P less than 0.005) and iron binding capacity also rose. Serum immunoglobulins did not change. The numbers of total lymphocytes (P less than 0.005) and CD8+ cells rose but CD4+ cells did not change. The tube and enteral feedings were well tolerated. These results demonstrate that enteral feeding may result in body-cell-mass repletion in malnourished AIDS patients. PMID- 1898580 TI - Protein quality of two liquid-formula diets used in nursing homes. AB - The protein quality of the liquid diet Two Cal HN was evaluated by plasma amino acid (PAA) ratio and by chemical score. The PAA test was performed in young healthy men, elderly healthy men, and elderly institutionalized, tube-fed men. In all three groups the PAA ratio for tryptophan was negative, indicating a deficiency of this amino acid in the formula's protein. But the amino acid score for tryptophan based on the manufacturer's stated amino acid composition was adequate (0.90). To resolve the discrepancy between PAA test and amino acid score, the formula's protein was isolated and its amino acid composition analyzed. In three samples of Two Cal HN, the tryptophan content of the isolated protein averaged only 45% of the content stated in the manufacturer's product description. A similar discrepancy was then found for Isocal, another liquid diet used in nursing homes. PMID- 1898581 TI - Prevalence of malnutrition and vitamin A deficiency in the Diourbel, Fatick, and Kaolack regions of Senegal: feasibility of the method of impression cytology with transfer. AB - The evaluation of the prevalence of ophthalmological diseases and vitamin A deficiency in Senegalese preschool-aged children enabled us to confirm the method of impression cytology with transfer (ICT) and to assess the impact of ophthalmological diseases on the cytological appearance of conjunctival cells. A simplification of the ICT method consisted of transferring cells present on a strip of paper to a glass slide by finger pressure. Harris-Schorr staining of the sample papers confirmed the results obtained by the transfer. Inflammatory trachoma influenced the results of the test. This simple method will prove very helpful for detection of vitamin A deficiency in children in underdeveloped areas. PMID- 1898582 TI - Prevalence of malnutrition and vitamin A deficiency in the Diourbel, Fatick, and Kaolack regions of Senegal: epidemiological study. AB - The purpose of our study was to determine the prevalence of protein-calorie malnutrition (PCM), ocular diseases, and vitamin A deficiency in preschool children selected at random in a rural zone of the groundnut belt of Senegal. The prevalence of PCM was 37.1% (95% CI 33.8-40.2%) according to the Waterlow classification, with a majority of stunting, and prevalence of hypovitaminosis A was estimated to be 11.4% (95% CI 9.3-13.5%) by using impression cytology. Furthermore, 19.4% (95% CI 15.8-22.0%) of the children might be defined at risk of deficiency. The prevalence of Bitot's spots was equal to 0.2% (95% CI 0.03 0.9%). A problem of PCM associated with a health-endangering vitamin A deficiency existed. PMID- 1898583 TI - Prevalence of malnutrition and vitamin A deficiency in the Diourbel, Fatick, and Kaolack regions of Senegal: a controlled study. AB - Two hundred and six Senegalese preschool children included in an epidemiological study were selected by their results from impression cytology with transfer (ICT) for assessment of their nutritional state by means of biological variables and for assessment of the diagnostic values of the ICT. A problem of protein-calorie malnutrition existed (transthyretin and retinol-binding protein concentrations were low) associated with vitamin A deficiency (retinol concentrations were low). The sensitivity and specificity of the ICT defined with respect to retinol (threshold fixed at 0.35 mumol/L) varied with the classification criteria of ICT and seemed to be fairly insensitive but specific. PMID- 1898584 TI - Vitamin B-6 metabolism in premature infants. AB - The response of premature infants to intravenous pyridoxine or pyridoxal was studied by measuring serum and erythrocyte pyridoxal 5'-phosphate (PLP). In the first study serum PLP was measured in 28 infants periodically through day 28. Infants less than 30 wk gestational age (GA) had no serum PLP response to the administration of pyridoxine. Infants greater than or equal to 30 wk GA had significantly greater concentrations of PLP by day 3. In the second study there was a negligible response of serum PLP in nine infants less than or equal to 28 wk GA to supplementation of pyridoxine or pyridoxal. However, erythrocyte PLP and whole-blood total vitamin B-6 concentrations increased in both groups, indicating the presence of a substantial amount of the vitamin in the circulation of the infants. Whereas the functional significance of these observations is not known, it appears that in premature infants, serum PLP may not be an appropriate indicator of vitamin B-6 status. PMID- 1898586 TI - Safety of factor VIII. PMID- 1898587 TI - Hepatitis C virus infection in hemophiliacs. PMID- 1898585 TI - Elimination of coincident Staphylococcus aureus nasal and hand carriage with intranasal application of mupirocin calcium ointment. AB - OBJECTIVE: To determine the safety and efficacy of mupirocin calcium ointment in the elimination of Staphylococcus aureus nasal and hand carriage in healthy persons. DESIGN: A double-blind, placebo-controlled, randomized trial. SETTING: Clinical research unit of a tertiary medical center. SUBJECTS: Health care workers with stable S. aureus nasal carriage. INTERVENTIONS: Subjects (n = 68) were randomly assigned to receive either mupirocin or placebo intranasally twice daily for 5 days. MEASUREMENTS AND MAIN RESULTS: Cultures of the hands and nares were obtained at baseline and 72 hours after therapy. The nares were also cultured 1, 2, 4, and 12 weeks after therapy. Antimicrobial susceptibility testing and restriction endonuclease analysis of plasmid DNA were used to confirm strain identity. There were no serious side effects. Mupirocin decreased the frequency of S. aureus nasal carriage at each time interval: At 3 months, 71% of subjects receiving mupirocin remained free of nasal S. aureus compared with 18% of controls. This difference (53%; 95% CI; 26% to 80%) was significant (P less than 0.0001). Additionally, analysis of plasmid patterns showed that 79% of subjects in the mupirocin group were free of the initial colonizing strain at 3 months. The proportion of hand cultures positive for S. aureus in the mupirocin group after therapy was lower than in the placebo group (2.9% compared with 57.6%). This difference (53%; 95 CI, 30% to 80%) was significant, after adjustment for the frequency of hand carriage at baseline (P less than 0.0001). CONCLUSIONS: When applied intranasally for 5 days, mupirocin calcium ointment is safe and effective in eliminating S. aureus nasal carriage in healthy persons for up to 3 months and appears to have a corresponding effect on hand carriage at 72 hours after therapy. PMID- 1898588 TI - The spindle is required for the process of sister chromatid separation in Drosophila neuroblasts. AB - We have studied two aspects of the process of sister chromatid separation in the Drosophila melanogaster neuroblasts. First, we analyzed the requirement of a functional spindle for sister chromatid separation to take place using microtubule depolymerizing drugs such as colchicine or a reversible analogue (MTC). Incubation of this tissue in colchicine causes the cells to block irreversibly at metaphase and no significant levels of sister chromatid separation were observed even after long periods of incubation. Exposure of neuroblasts to MTC also causes cells to block at metaphase, but after reversion most of the cells enter anaphase and are thus able to complete sister chromatid separation. These results imply that a functional spindle is required for sister chromatid separation. Second, we studied the role of heterochromatin during chromatid pairing and subsequent separation in chromosomes which carry either one or two extra pieces of heterochromatin. The results indicate that sister chromatids establish strong pairing along the translocated heterochromatin. During the early stages of anaphase, these chromosomes separate first the centromeric region and later the regions bearing extra heterochromatin. These results indicate that constitutive heterochromatin plays an important role for sister chromatid pairing and might be involved in the process of separation. PMID- 1898589 TI - Localization of ras antigenicity in rat hepatocyte plasma membrane and rough endoplasmic reticulum fractions. AB - We have examined the antigenicity of plasma membrane (PM) and rough microsomal (RM) fractions from rat liver using anti-ras monoclonal antibodies 142-24EO5 and Y13-259 and immunochemistry as well as electron microscope immunocytochemistry. Proteins immunoprecipitated with monoclonal antibody 142-24E05 were separated using single-dimensional gradient-gel electrophoresis. The separated proteins were then blotted onto nitrocellulose sheets and incubated with [alpha-32P]GTP. Radioautograms of blots indicated the presence of specific 21.5- and 22-kDa labeled proteins in the PM fraction. A 23.5-kDa [alpha-32P] GTP-binding protein was detected in immunoprecipitates of both PM and RM fractions. Monoclonal antibody Y13-259 reacted only with the 21.5-kDa [alpha-32P] GTP-binding protein in the plasma membrane fraction. When anti-ras monoclonal antibody 142-24E05 and the immunogold technique were applied to membrane fractions using a preembedding immunocytochemical method, specific labeling was observed in association with both vesicular structures and membrane sheets in the PM fraction but only with electron-dense vesicular structures in the RM fraction. Thus ras antigenicity is associated with hepatocyte plasma membranes and ras-like antigenicity is probably associated with vesicular (secretory/endocytic) elements in both plasma membrane and rough microsomal preparations. PMID- 1898590 TI - Abnormal behavior of the yolk centrosomes during early embryogenesis of Drosophila melanogaster. AB - After the 10th nuclear cycle the yolk centrosomes follow an irregular pathway. Unlike the somatic centrosomes, which move to the opposite poles of the nuclei to form the bipolar spindles, the yolk centrosomes remain as pairs at one pole of the yolk nuclei or shift feebly and nucleate irregular spindles, most of which have only one main pole. The yolk centrosomes are no longer observed near the yolk nuclei, but progressively move away into the surrounding cytoplasm. Despite the irregular behavior of the centrosomes and although the yolk nuclei cease to divide, the yolk centrosome duplication cycle continues. The early development of Drosophila thus provides an excellent natural system for the study of the uncoupling of the nuclear and centrosomal cycles. PMID- 1898591 TI - Serum inhibition of proliferation of serum-free mouse embryo cells. AB - Serum-free mouse embryo (SFME) cells, derived in medium supplemented with insulin, transferrin, high density lipoprotein, epidermal growth factor, and fibronectin, do not undergo crisis, maintain a predominantly diploid karyotype with no detectable chromosomal abnormalities for well over 100 population doublings in vitro, and are growth inhibited by concentrations of serum that are growth-stimulatory for most cell lines in culture. Serum inhibition of SFME cell proliferation was reversible and was not prevented by addition of the supplements of the serum-free medium, even when added repeatedly during the culture period. The serum effect on SFME cell proliferation could be detected after incubation in serum-containing medium for as little as 8 h. SFME cells in serum-containing medium were arrested in the G1 phase of the cell cycle with a greatly reduced rate of incorporation of precursors into DNA and thymidine kinase activity, while a reduction in rate of incorporation of amino acids into protein was not observed. SFME cultures maintained for extended periods in serum-containing medium underwent a crisis-like period followed by the appearance of variant cells capable of growing in serum-supplemented medium. These cells exhibited abnormal karyotype and were resistant to several inhibitors of proliferation active on the parent SFME cell type. PMID- 1898593 TI - Reversible effects of sodium butyrate on the differentiation of F9 embryonal carcinoma cells. AB - We have studied effects of sodium butyrate on embryonal carcinoma F9 cell differentiation. In the presence of sodium butyrate, F9 cells underwent rapid and drastic morphological changes and expressed marked increases in mRNA levels of various differentiation markers. When sodium butyrate was removed from the cultures, all the examined phenotypes of F9 cell differentiation rapidly reverted to the characteristics of undifferentiated stem cells. However, under the same conditions, when cycloheximide or actinomycin D was added to the cultures, such phenotypic reversion was not observed, but high mRNA levels of the differentiation markers as well as altered cell morphology were retained. These results indicated that the effects of sodium butyrate on induction of teratocarcinoma cell differentiation were reversible and that de novo syntheses of some mRNA(s) and protein(s) were necessary for the reversion of differentiated cells to stem cells. PMID- 1898592 TI - Mechanisms of cAMP-mediated gene induction: examination of renal epithelial cell mutants affected in the catalytic subunit of the cAMP-dependent protein kinase. AB - The precise mechanistic role of the cAMP-dependent protein kinase (cAMP-PK) in cAMP-mediated gene induction remains unclear. Renal epithelial cell mutants were compared to the LLC-PK1 parental cell line for induction of the cAMP-responsive urokinase-type plasminogen activator (uPA) gene, as quantitated by the technique of mRNA solution hybridization. The FIB4 and FIB6 mutants, which possess less than 10% parental cAMP-PK catalytic (C) subunit activity, showed markedly diminished uPA mRNA induction in response to agents elevating intracellular cAMP such as the cAMP analogue 8-bromo-cAMP and the adenylate cyclase-stimulating hormones vasopressin and calcitonin. In contrast, the mutant cells responded to a similar or greater extent than the parental cells in terms of uPA mRNA induction following treatment with the Ca2+/phospholipid-dependent protein kinase activator phorbol 12-myristate 13-acetate (PMA). Elevation of intracellular cAMP was found to induce a translocation of the cAMP-PK C subunit from the perinuclear Golgi region to the nucleus in both parental and mutant cell lines, as shown by immunocytochemical techniques. Results argue for the role of the cAMP-PK C subunit activity and possibly nuclear translocation of the C subunit in cAMP mediated uPA induction, which is mechanistically distinct from the PMA-stimulated response. PMID- 1898594 TI - Disruption of the cytoskeleton with cytochalasin D induces c-fos gene expression. AB - The treatment of exponentially growing HeLa cells and quiescent WI-38 cells with cytochalasin D, which disrupts the cytoskeletal microfilaments, results in a rapid and marked increase in the transcription of the c-fos protooncogene with a concomitant increase in c-fos mRNA steady-state levels. Transcription of rRNA, HLA-B7, and H4 histone genes was not significantly affected by the drug treatment. These results suggest that the nucleus can respond to signals related to the structural organization of the cytoskeleton and selectively adjust the regulation of gene expression. PMID- 1898595 TI - Early in vitro genesis and differentiation of axons and dendrites by hippocampal neurons analyzed quantitatively with neurofilament-H and microtubule-associated protein 2 antibodies. AB - Differentiating neurons initially extend neurites that are the precursors of axons and dendrites. The temporal pattern of neurite outgrowth has been studied extensively, but mostly qualitative analyses have been used to study this phenomenon. We have examined neurite outgrowth of hippocampal neurons in primary cultures using a polyclonal antibody against microtubule-associated protein 2 (MAP2) and a novel monoclonal antibody against the phosphorylated form of high neurofilament subunit (NF-H). These antibodies serve as markers for dendrites and axons, respectively. The neurite staining patterns were quantified during the first 10 days in culture and the analysis revealed that primary processes undergo three phases of differentiation: (i) in the first 24 h, the majority of primary neurites express MAP2 only and a small percentage express both MAP2 and NF-H; (ii) between 24 and 48 h, NF-H expression increases and it is coexpressed with MAP2 in many neurites as they begin to lengthen; and (iii) between 48 h and 4 days, MAP2 and NF-H protein expression occurs in separate populations of neurites. While most of the earliest forming primary neurites appear to be dendritic (MAP2 only), the coexpression of dendritic and axonal protein markers in a group of early forming processes suggests that these neurites may not be predetermined to become a dendrite or an axon. Our data also indicate that NF-H is detectable early in primary neurite development and that, based on in vivo localization and morphology of cultured neurites, the phosphorylated form of NF-H is concentrated in axons. PMID- 1898596 TI - Ig H and L chain contributions to autoimmune specificities. AB - An Ig H chain expression vector has been constructed by using the V region of 3H9, an antibody that binds ssDNA, dsDNA, and cardiolipin. The H chain construct was transfected into six hybridoma cell lines expressing Ig L chains. All resulting H and L chain combinations had at least some affinity for ssDNA, whereas five also bound dsDNA to a similar degree as 3H9. The loss of dsDNA binding was correlated with a single amino acid difference between two V kappa 8 L chains. A further characteristic of 3H9, its immunofluorescent staining pattern, was shared by four of the recombinant antibodies, whereas its specificity for cardiolipin was shared with five. The transfections reported here show that a V kappa 3 L chain confers specificity for an RNA-associated epitope and that a V kappa 21E L chain prevents cardiolipin binding. These experiments suggest that the 3H9 H chain contributes essential determinants required for binding to DNA as well as cardiolipin but that L chains can modulate or prevent this binding. L chains may also expand the specificity of a recombinant antibody. PMID- 1898597 TI - Biochemical characterization and tissue distribution of hamster complement C1s. AB - Several mAb (PG11, NG7, and ED4) against hamster complement C1s were obtained. PG11 and NG7 were shown to cross-react with human and rat C1s. By using an immunohistochemical method, we examined localization of C1s in tissues of hamsters and rats. Present results revealed a widespread yet specific staining of hamster C1s which is associated with endoderm-, mesoderm-, and neuroectoderm derived cells. For example, chondrocyte of hyaline cartilage and surface epithelium of the stomach were strongly positive. Intestinal epithelium, muscle cells, pia mater and epithelium of the choroid plexus of the ventricle, and hepatocytes were also stained. The synthesis of hamster C1s in these organs was confirmed by RNA blot hybridization. Secretion of C1s into the culture medium was revealed by immunoblot analysis in cell lines of hepatocytes, kidney cells, and myoblasts of rat or hamster. PMID- 1898599 TI - The mast cell-committed progenitor. In vitro generation of committed progenitors from bone marrow. AB - Mast cell-committed progenitors are detected in the unique microenvironment of the mesenteric lymph node (MLN) of Nippostrongylus brasiliensis-infected mice but not in naive bone marrow. We have determined that MLN cells, after infection, produce high levels of IL-3, IL-4, and IgE, presumably in the form of immune complexes with antigens produced by the infecting helminth. After N. brasiliensis infection, peak production of these factors occurs several days before the peak appearance of mast cell-committed progenitors in the MLN. To determine if these factors play a role in mast cell commitment, we recreated these conditions, in vitro. Naive bone marrow cells were cultured with combinations of IL-3, IL-4, and IgE immune complexes, or on IgE-coated plates, and then assayed for acquisition of the ability to form mast cell colonies when supplemented with fibroblast conditioned medium alone. IL-3 and IgE immune complexes, and, unexpectedly, IgE immune complexes alone were found to be capable of producing mast cell-committed progenitors, i.e., cells responsive to fibroblast-conditioned medium alone, from bone marrow, whereas IL-4 did not enhance production of mast cell-committed progenitors from bone marrow. Production of IFN-gamma peaked at the same time point as committed progenitor activity and may be responsible for down regulating the response. PMID- 1898598 TI - Anti-idiotype-induced, lipopolysaccharide-specific antibody response to Pseudomonas aeruginosa. II. Isotype and functional activity of the anti-idiotype induced antibodies. AB - We recently developed a murine anti-idiotypic mAb that functioned as a molecular mimic of the O-specific polysaccharide side chain (Ps) of Pseudomonas aeruginosa LPS in vitro, and which induced Ps-specific antibodies in syngeneic BALB/c ByJ mice. In the current studies, we demonstrate that these anti-Id-induced, Ps specific antibodies fix complement to the bacterial cell surface, and protect neutropenic mice from fatal P. aeruginosa sepsis. The isotypic distribution of the anti-Id-induced antibodies, however, resembles the restricted pattern (IgM and IgG3) seen after administration of purified Ps to mice. The immunogenicity and number of isotypes of Ps-specific antibody produced could be enhanced by conjugating the anti-Id to keyhole limpet hemocyanin. Finally, the anti-Id administered before immunization with purified Ps, primed BALB/c ByJ mice for production of other Ps-specific antibody isotypes (IgG1). These studies show that this anti-Id induces functional anti-Ps antibodies in syngeneic mice, and when used in conjugate form or as a priming agent before Ps immunization, yields an antibody response consistent with "T cell dependence." These immunization strategies may be useful for the induction of polysaccharide-specific antibodies in man. PMID- 1898600 TI - Macrophage activation for intracellular killing as induced by calcium ionophore. Correlation with biologic and biochemical events. AB - Changes in the concentration of cytosolic Ca2+ are known to affect various macrophage functions; in particular, exposure in vitro to the Ca2+ ionophore A23187 primes macrophages for tumor cell killing. In the present report, it is shown that treatment with this ionophore similarly mimics IFN-gamma as a priming signal for induction of microbicidal activity. Incubation of mouse bone marrow derived macrophages with 10(-7) to 10(-6) M A23187 (in the presence of Ca2+) led to intracellular killing of the protozoan parasite Leishmania enriettii within 24 h, provided LPS (1 ng/ml) was also present; no microbicidal activity was observed using either compound alone. A 4-h exposure to the ionophore in the presence of Ca2+ (priming phase) was sufficient to induce leishmanicidal activity upon reincubation with LPS, here acting as a necessary second signal. Addition of EGTA during the priming phase blocked intracellular killing upon subsequent LPS treatment; microbicidal activity could be restored by excess Ca2+, but not Mg2+, suggesting that changes in the concentration of cytosolic Ca2+ are sufficient to mediate the molecular events that lead to acquisition of microbicidal potential. Ionophore-induced leishmanicidal activity was paralleled by a stimulation of the hexosemonophosphate shunt pathway and production of nitrites, which are biochemical correlates of the activated state. In addition, sequential exposure to A23187 and LPS markedly stimulated macrophages to release TNF and PGE2, two agents thought to act as modulators of macrophage activation. PMID- 1898601 TI - Natural killer cell-dependent mycobacteriostatic and mycobactericidal activity in human macrophages. AB - Host defense mechanisms against Mycobacterium avium complex (MAC) are poorly understood. Recent evidence suggests the role of NK cells in the host defense against some intracellular pathogens. We investigated whether NK cells play a role in MAC infection. IL-2-activated human NK cells were incubated with human monocyte-derived macrophages either before or after infection with MAC. Macrophages were lysed 3 and 5 days after infection for quantitation of viable intracellular organisms. Although no killing was observed by nonstimulated macrophages, exposure to IL-2-treated NK cells for 24 h before infection induced macrophage to kill 70 +/- 8% of intracellular MAC by 3 days, and 81% +/- 4% in 5 days (p less than 0.01 for both compared with control). Killing was not blocked by incubation with anti-TNF antibody (Ab) or anti-IFN-gamma Ab. Similarly, incubation of macrophages for 24 h with supernatant obtained from IL-2 activated NK cells was associated with 74 +/- 4% killing of intracellular MAC in 3 days and 81 +/- 6% in 5 days (p less than 0.01 for both compared with control). However, the supernatant-mediated activation was partially blocked by anti-TNF Ab (46 +/- 6%; p less than 0.05) but not by anti-IFN gamma Ab. When infected macrophages were incubated with NK cells 24 h after infection for 48 h, they killed 54 +/- 3% of intracellular M. avium in 3 days and 73 +/- 5% in 5 days (p less than 0.02 for both compared with control). This effect was also not blocked by either anti-TNF or anti-IFN gamma Ab. These results suggest that activated NK cells may have an important role in the intracellular killing of MAC and that the NK-mediated activation of macrophages is in part mediated by TNF. PMID- 1898602 TI - Phagocytosis of Leishmania enhances macrophage activation by IFN-gamma and lipopolysaccharide. AB - This investigation describes the ability of Leishmania promastigotes to enhance activation of bone marrow-derived murine macrophages in vitro if added together with rIFN-gamma in the presence or absence of LPS. Activation was defined as the capacity for arginine-derived NO2- production and the killing of intracellular Leishmania. Enhanced NO2- production was observed for either CBA or C3H/HeJ macrophages undergoing phagocytosis at the time of activation. Other phagocytic stimuli including inert polystyrene latex beads were as effective as Leishmania. No correlation could be demonstrated between the enhanced NO2- release and secretion of products of the respiratory burst or PGE2. However, TNF-alpha secretion was elevated in cultures undergoing phagocytosis and a relationship between hexosemonophosphate shunt activity and NO2- levels was evident. These studies confirm and extend previous reports that phagocytosis plays an important role in the regulation of macrophage physiology. PMID- 1898603 TI - Entry of antivirally active T lymphocytes into the thymus of virus-infected mice. AB - The thymus has long been regarded as an immunologically "privileged site" by being shielded against the entry of exogenous Ag as well as protective elements of the immune system. After i.p. infection of mice, the lymphocytic choriomeningitis virus multiplied in this organ. Viral Ag was found predominantly in the epithelial-reticular cells of the medulla and to a lesser extent in such cells of the cortex. Beginning on day 7 after infection, the virus disappeared, a process that could be blocked by depleting the mice of peripheral T lymphocytes or of CD8+ cytotoxic T lymphocytes. Viral clearance was accelerated by i.v. injection of splenocytes from mice, which themselves were just eliminating the virus. CD8+ cells from CD8-congenic donor mice, most with blast morphology, were detected immunocytochemically in the thymus, predominantly in the medulla. A few CD8+ T lymphocytes from donors not previously infected were also demonstrated in the thymic tissue of infected mice. Our findings indicate that the lymphocytic choriomeningitis virus has access to the thymus and suggest that it is cleared by the antiviral activity of circulating cytotoxic T lymphocytes. Thus, just as other organs, the thymus appears to be subject to immune surveillance by mature T lymphocytes that have their origin in secondary lymphoid tissues. PMID- 1898604 TI - The role of cytophilic IgG3 antibody in T cell-mediated resistance to infection with the extracellular bacterium, Pseudomonas aeruginosa. AB - Previous studies have demonstrated that T lymphocytes from mice immunized with a high m.w. polysaccharide Ag from Fisher-Devlin immunotype I Pseudomonas aeruginosa can adoptively transfer protection against challenge with the homologous bacterial strain to susceptible mice. This T cell-mediated resistance has been found to be B cell dependent, although serum from immunized mice is incapable of passively transferring protection to nonimmune mice. The current studies demonstrate that T cells from immunized mice possess receptors that permit them to be adsorbed to IgG3-secreting hybridomas, but not to IgM-secreting hybridomas. Cross-linking of antibody on the surface of immune T cells results in release of a soluble factor that inhibits bacterial growth. Treatment of T cells to remove cytophilic antibody eliminates their ability to adoptively transfer protection to nonimmune mice, and the protective ability can be restored by co incubating the T cells with monoclonal P. aeruginosa-specific IgG3 antibody before adoptive transfer to nonimmune mice. These observations are consistent with a model in which T lymphocytes from immunized mice are activated by cross linking of FcR for IgG3 to secrete an antibacterial lymphokine. The ability of IgG3 at low antibody concentrations to act synergistically with T lymphocytes to inhibit bacterial growth could explain the evolutionary selection of this antibody isotype as the predominant subclass of IgG secreted in response to bacterial capsular polysaccharide Ag. PMID- 1898605 TI - Suppression of human monocyte function against Candida albicans by autologous IL 2-induced lymphokine-activated killer cells. AB - We have previously reported that IL-2-induced lymphokine-activated killer (LAK) cells have the capacity to lyse autologous and allogeneic monocytes. To understand the biologic significance of this interaction, we investigated the function of human monocytes against the opportunistic pathogen, Candida albicans, subsequent to a short exposure to autologous LAK cells. A highly sensitive radiolabel assay, which makes use of the incorporation of [3H]glucose into residual Candida after their incubation with monocytes, was developed to measure antifungal activity. Cultured monocytes, after 2 to 6 h exposure to LAK cells, were found to be substantially suppressed in their ability to control fungal growth. Moreover, monocytes cultured in the presence of granulocyte/macrophage (GM)-CSF or IL-3, were even more suppressed in function after a short incubation with LAK cells. The effect of GM-CSF was both time and dose dependent, with peak susceptibility induced after 4 days of culture with as little as 10 U/ml of the cytokine. These GM-CSF-cultured monocytes, however, were relatively resistant to inhibition by freshly isolated large granular lymphocytic NK cells. Therefore, IL 2 induces in large granular lymphocytic cells the capacity to inhibit monocyte function. In contrast to GM-CSF and IL-3, IFN-gamma was found to have a protective effect on monocytes, because monocytes cultured 4 days in IFN-gamma were not significantly inhibited by LAK cells. These results indicate that LAK cells may be involved in regulation of monocyte function and suggest that the state of differentiation induced by different cytokines may dictate the level of control of the monocytes by LAK cells. PMID- 1898606 TI - A shared kappa reciprocal fragment and a high frequency of secondary Jk5 rearrangements among influenza hemagglutinin specific B cell hybridomas. AB - Ig kappa-chain gene rearrangement results in the displacement or loss of the DNA immediately 5' of Jk. This retained DNA is found on a different size fragment than in the germline (a reciprocal fragment), and contains the reciprocal joint of rearranged Vk and Jk genes, the back-to-back fusion of the heptamer/nonamer recombination signals. B cells of independent origin rarely have reciprocal fragments of the same size. However, we report that 9 of 15 B cell hybridomas of independent origin have reciprocal fragments of the same size (8-kb BamHI fragments) unrelated to their productive rearrangements. An 8-kb reciprocal fragment has also occurred on about 25% of the kappa alleles of normal splenic B cells. We find that the reciprocal fragments in two of these hybridomas contain the reciprocal joints of Jk1 genes and different Vk8 genes. In addition, we find that at least 8 of the 12 Jk4 or Jk5 expressing hybridomas have undergone double recombinations on their productive kappa alleles. The implications of these findings on the high frequency of 8-kb reciprocal rearrangements and on Vk rearrangement are discussed. PMID- 1898608 TI - IFN-gamma inhibits inflammatory cell recruitment and the evolution of bacterial cell wall-induced arthritis. AB - Localization of streptococcal cell wall Ag (SCW) in the synovial tissue of treated rats induces an influx of leukocytes and a cell-mediated immune response leading to arthritis and joint destruction. Systemic administration of the T cell product, IFN-gamma (10(6) U/kg/day), suppresses the recruitment of leukocytes into the synovium and effectively inhibits the inflammation and pathology characteristic of SCW-induced arthritis (articular index 10.4 +/- 0.6 for SCW vs 2.0 +/- 0.7 for SCW with IFN-gamma, p less than 0.005). Monocyte-macrophages from animals treated with IFN-gamma exhibited defective chemotactic responses when tested in vitro and furthermore, monocytes cultured with IFN-gamma (25 to 500 U/ml) in vitro had significantly suppressed chemotactic responses to the complement fragment C5a (p less than 0.005). The decreased ability to migrate to C5a was associated with decreased binding of fluorochrome-conjugated C5a indicative of reduced expression of C5a receptors. Based on these data, IFN-gamma that induces monocyte maturation as reflected by increased Ia expression conversely inhibits C5a receptor expression. Although locally elevated IFN-gamma levels may serve to inhibit recruitment away from an inflammatory site, systemic exposure to IFN-gamma appears to inhibit leukocyte recruitment to the inflammatory site by its ability to induce premature maturation and concomitant inability to respond to certain chemotactic ligands. Inasmuch as monocyte recruitment to the synovium is pivotal in the development of SCW-induced polyarthritis, the ability of IFN-gamma to inhibit this event effectively inhibits the synovial pathology. PMID- 1898607 TI - The expression of the Ig H chain repertoire in developing bone marrow B lineage cells. AB - Analyses of rearranged Ig H chain V region genes of bone marrow pre-B cells demonstrate extensive sequence diversity, particularly within the third hypervariable region (HCDR3). This diversity is constrained, however, through preferential utilization of certain D gene segments and possibly VH gene segments and a preponderance of productive rearrangements, primarily those expressing D gene segments in a preferred reading frame. The predominance of productively rearranged V genes with D regions translated in a preferred frame, is, at least in part, the consequence of selective clonal expansion encompassing at least five to six divisions subsequent to VH-D-JH rearrangement. Selection for clonal expansion appears to be dependent on recognition of the nascent H chain product of certain productively rearranged genes. PMID- 1898609 TI - Chemical synthesis and seroreactivity of a neoantigen containing the oligosaccharide hapten of the Mycobacterium tuberculosis-specific phenolic glycolipid. AB - The report of a major triglycosyl phenol phthiocerol (phenolic) glycolipid in some strains of Mycobacterium tuberculosis that resembles the phenolic glycolipid I of Mycobacterium leprae raised the prospects of a specific serodiagnostic tool for human tuberculosis. The terminal diglycosyl unit of the M. tuberculosis product was synthesized and converted to a corresponding neoglycoprotein, the O (2,3,4-tri-O-methyl-alpha-L-fucopyranosyl)-(1----3)-O-alpha-L- rhamnopyranosyl) (1----9)-oxynonanoyl-bovine serum albumin, and applied, in ELISA, to sera from individuals with tuberculosis. Although the correlation coefficient between the synthetic product and the native glycolipid was excellent, the seroreactivity rate of tuberculous sera was disappointing; only 24 of 119 sera from tuberculosis patients showed evidence of anti-glycolipid antibodies. In isolates of M. tuberculosis from tuberculosis patients the glycolipid was present in only 1 of 11. A partially deglycosylated version was present in two other isolates; however, most isolates lacked the glycolipid. Accordingly, while the results, unlike those of others, do not portend a future for this form of serodiagnosis in the management of tuberculosis, they offer intriguing hints as to the basis of the variable immunogenicity and pathogenicity of strains of M. tuberculosis. PMID- 1898610 TI - Relationship between chemical composition and biological function of Pseudomonas aeruginosa lipopolysaccharide: effect on human neutrophil chemotaxis and oxidative burst. AB - There are conflicting data on the effect of bacterial lipopolysaccharides (LPS) on the function of human neutrophils. The present study was designed to examine the relationship between chemical composition and the modulatory effect of LPS on human neutrophil function. LPS was extracted from five strains of Pseudomonas aeruginosa isolated from cystic fibrosis patients by the hot phenol-water method. Chemical characterization included neutral sugars, amino components, and fatty acids. Neutrophils isolated from peripheral blood of healthy individuals were preincubated with different concentrations of LPS. After preincubation, the chemotaxis and chemiluminescence of neutrophils to various stimuli were determined. It was shown that LPS from different strains did not exert the same degree of regulatory effect on neutrophil functions. LPS from strain 174-O:9 exerted the most pronounced effect on neutrophil function seen as inhibition of neutrophil chemotaxis toward the chemotactic peptide f-Met-Leu-Phe and zymosan activated serum (ZAS) and priming of the cells for less than or equal to 8-fold enhancement of chemiluminescence response to f-Met-Leu-Phe. Conversely, LPS from strain 1118-O:3 had no effect on neutrophil chemotaxis and a slight effect on chemiluminescence. The major differences in chemical composition of the LPS from these two strains are in the rhamnose and heptose content of the O side chain and in the alanine content of the core region. These data indicate that chemical composition of the LPS molecule may play an important role in biological activity of LPS. PMID- 1898611 TI - Effects of TNF alpha on the expression of class II MHC molecules in macrophages induced by IFN gamma: evidence for suppression at the level of transcription. AB - Tumor necrosis factor-alpha (TNF-alpha) induces surface expression of class II major histocompatibility (MHC) molecules (la molecules) in many cells, including macrophage-like cell lines. When we tested the effects of this cytokine on murine peritoneal macrophages, TNF alpha had little effect on surface expression of la. The strong expression of such molecules induced by interferon-gamma (IFN gamma) was, however, suppressed moderately by TNF alpha. These effects were reflected at the level of specific messenger RNA (mRNA) as detected by Northern blot analysis. Furthermore, the locus of control appears to be transcriptional; in nuclear run on assays, TNF alpha suppressed the IFN gamma-induced enhancement of transcription for the murine beta-chain of I-A (I-A beta.). Taken together the data suggest that TNF alpha has little effect on class II MHC genes and surface expression in murine peritoneal macrophages, that TNF alpha is a modest suppressant of such molecules when their levels are raised by IFN gamma, and that these suppressive effects are mediated at the level of transcription. PMID- 1898612 TI - Stimulus-dependent leukotriene release from human basophils: a comparative study of C5a and Fmet-leu-phe. AB - Previous studies of human basophil mediator release have noted that the bacterial peptide fmet-leu-phe and the anaphylatoxin C5a induce comparable levels of histamine release while only fmet peptide induces leukotriene release. Since 5 lipoxygenase metabolism of arachidonic acid is calcium dependent, we examined the characteristics of the human basophil [Ca++]i response which follows its activation by either fmet peptide or C5a. While the peak [Ca++]i response was essentially identical for these two stimuli, fmet peptide induced a prolonged increase in [Ca++]i while C5a stimulated only a transient increase in [Ca++]i that was essentially over within 2 minutes of adding the stimulus. Simultaneous addition of EDTA with fmet peptide revealed the two phases of the [Ca++]i response and demonstrated that leukotriene release was dependent on an elevated [Ca++]i level in the 2-5 minutes following challenge. Enhancement of leukotriene release induced by C5a by agents such as staurosporine and interleukin-3 also produced a [Ca++]i kinetic curve which resembled fmet peptide. Single cell studies of the [Ca++]i response could detect no subpopulations of cells which responded preferentially to fmet peptide or C5a, eliminating the possibility that the ability of fmet peptide to induce leukotriene was a result of its action on a functionally distinct population of basophils. PMID- 1898613 TI - Modulation of Mycobacterium avium growth in murine macrophages: reversal of unresponsiveness to interferon-gamma by indomethacin or interleukin-4. AB - The ability of soluble factors to modulate the growth of a virulent strain of Mycobacterium avium in murine peritoneal macrophages was studied. The virulent strain, TMC 702, grew progressively in the organs of susceptible BALB/C mice. In addition, this strain of M. avium grew progressively in untreated peritoneal macrophages. Treatment of macrophage monolayers with interferon-gamma (IFN-gamma) did not change significantly the intracellular growth of M. avium. Addition of indomethacin to IFN-gamma-treated macrophage monolayers rendered them significantly more bacteriostatic than macrophages treated with interferon alone, suggesting a role for prostaglandins in inducing unresponsiveness to IFN-gamma in infected cells. Additionally, treatment with tumour necrosis factor-alpha led to a modest increase in bacteriostasis, as compared to untreated monolayers. Further experiments with recombinant interleukins showed that interleukin-4 (IL-4), on its own, could increase bacteriostatic activity against M. avium in a reproducible fashion. Experiments with interleukin combinations showed that IFN gamma and IL-4 treatment of macrophages rendered these cells almost fully bacteriostatic against M. avium, inclusion of scavengers of reactive oxygen species did not modify the beneficial effect of IFN-gamma and IL-4. Overall, our results suggest an important role for interleukins in modulating the interaction between virulent mycobacteria and murine macrophages. PMID- 1898614 TI - Interferon-gamma induced resistance to Legionella pneumophila in susceptible A/J mouse macrophages. AB - Legionella pneumophila (Lp) grow in cultures in human, guinea pig, and mouse macrophages from A/J strain mice. Because exudate macrophages from this strain of mice have been reported deficient in responsiveness to lymphokines, we thought it of interest to document the extent of responsiveness to interferon-gamma in the context of growth restriction of Lp. Peritoneal exudate macrophages were obtained from A/J mice and cultured in either the presence or absence of recombinant interferon-gamma. These cultures were then infected with Lp and the extent of bacterial growth estimated 48 hr later by means of a colony-forming unit (CFU) assay and electron microscopy. Interferon-gamma treatment significantly restricted the number of CFUs in the culture at concentrations as low as 20 U/ml, but did not affect the uptake of bacteria by macrophages. Furthermore, treatment with interferon induced morphological changes consistent with activated macrophages. The involvement of oxygen-dependent mechanisms in phagocyte killing and growth restriction was examined by the use of inhibitors such as superoxide dismutase (SOD) and catalase. Neither one of these inhibitors of toxic oxygen metabolites affected the interferon-gamma-induced suppression of Lp growth. These results suggest that although thioglycolate-induced exudate macrophages from A/J mice support the growth of Lp, these cells readily respond to the activating influence of interferon-gamma. Furthermore, lymphokine treatment does not inhibit Lp uptake by macrophages and apparently restricts the growth of bacteria by mechanisms independent of the activity of toxic oxygen metabolites. PMID- 1898615 TI - Tests help nail down HCV--but not entirely. PMID- 1898616 TI - Against minimalism in breast cancer follow-up. PMID- 1898617 TI - Multichannel cochlear implant and electrically evoked auditory brainstem responses in a child with labyrinthitis ossificans. AB - Ossification of the cochlea following meningitis presents a surgical challenge. Electrode mapping, especially in the young child, is difficult given the uncertainty of electrode contact with viable neural elements. This paper reviews surgical technique and the use of auditory brainstem responses to map the electrodes. A 4-year-old child deafened by meningitis at age 20 months had bilateral cochlear ossification by computed tomography. At surgery, a canal wall down mastoidectomy and closure of the ear canal were performed. A trough around the modiolus was drilled, and the electrode array was placed in it. Post operatively, the patient gave aversive or no responses to electrode stimulation. To assess electrode function, auditory brainstem responses to individual electrode activation were obtained under general anesthesia. Functioning electrodes could thus be selected for mapping. The patient now responds well to sound. PMID- 1898618 TI - Characterization of a novel aldose reductase inhibitor, FR74366, and its effects on diabetic cataract and neuropathy in the rat. AB - FR74366 (FK366) ([3-(4-bromo-2-fluorobenzyl)-7-chloro-2,4-dioxo-1,2,3,4- tetrahydroquinazolin-1-yl] acetic acid) is a chemically novel aldose reductase (AR) inhibitor. It exhibited a highly potent, reversible, and mixed type inhibition of partially purified AR from the rat sciatic nerve (IC50 = 3.6 nmol/L) and rat lens (IC50 = 4.4 nmol/L). FR74366 inhibited sorbitol accumulation in the isolated human erythrocyte (IC50 = 1.6 mumol/L), rat lens (IC50 = 39 mumol/L), and rat sciatic nerve (IC50 = 17 mumol/L) incubated with high glucose concentrations. The oral administration of FR74366 to streptozotocin (STZ) induced diabetic rats for 2 weeks decreased sorbitol levels (ED50 = 3.7 mg/kg for sciatic nerve, 23 mg/kg for lens, 52 mg/kg for retina, and 62 mg/kg for renal cortex). Administration of FR74366 to diabetic rats for 17 weeks delayed cataract formation and admixture of 0.028% FR74366 in the diet completely inhibited the cataract formation. Moreover, the recovery of reduced motor nerve conduction velocity by FR74366 in diabetic rats was demonstrated in prevention and reversal experiments. This recovery effect correlated well with reduction of accumulated sorbitol and fructose levels and normalization of decreased myoinositol levels. The duration and tissue specificity of inhibitory effects of FR74366 on sorbitol accumulation also correlated well with the levels of FR74366 in various tissues of diabetic rats. These data indicate that both decreases in tissue sorbitol levels and improvement of functional defects reflect FR74366 levels in tissue rather than plasma in diabetic rats. These results, taken together, suggest that FR74366, which is currently undergoing clinical trials in Japan and the United States, will be a useful therapeutic agent for diabetic complications. PMID- 1898619 TI - Exocrine pancreatic dysfunction in malnourished Australian aboriginal children. AB - Pancreatic exocrine dysfunction has been frequently recorded in protein-energy malnutrition in underdeveloped countries. In addition, the pancreas requires optimal nutrition for enzyme synthesis and potentially correctable pancreatic enzyme insufficiency may play a role in the continuation of protein-energy malnutrition. This problem has not been previously evaluated in Australian Aborigines. We have applied a screening test for pancreatic dysfunction (human immunoreactive trypsinogen [IRT] assay) to the study of 398 infants (6-36 months) admitted to the Alice Springs Hospital over a 20-month period. All infants were assessed by anthropometric measures and were assigned to three nutritional groups (normal, moderate or severely malnourished) and two growth groups (stunted or not stunted). Of the 198 infants who had at least a single serum cationic trypsinogen measurement taken, normal values for serum IRT (with confidence limits) were obtained from 57 children, who were normally nourished. IRT levels were significantly correlated with the degree of underweight but there was no correlation with the degree of stunting or age. Mean IRT levels for the moderate and severely underweight groups were significantly greater than the mean for the normal group (P less than 0.01). Seventeen children (8.6%) had trypsinogen levels in excess of the 95th percentile for the normally nourished group, reflecting acinar cell damage or ductal obstruction. We conclude that pancreatic dysfunction may be a common and important overlooked factor contributing to ongoing malnutrition and disease in malnourished Australian Aboriginal children. PMID- 1898620 TI - Pilot study of a household survey to determine HIV seroprevalence. AB - A survey based on a probability sample of U.S. households was suggested as a method to determine the number of persons infected with human immunodeficiency virus (HIV). To test the feasibility of such a survey, CDC's National Center for Health Statistics (NCHS) recently conducted a pilot study in two sites through a contract with the Research Triangle Institute. The first field test, conducted in January 1989, used a random sample of adults from households in Allegheny County (Pittsburgh), Pennsylvania; the response rate of 81% suggested that the majority of the sample population might participate in a carefully planned household HIV survey. This report summarizes the second field test, which was conducted in Dallas County, Texas, from September through December 1989. PMID- 1898621 TI - Health and nutritional status of Liberian refugee children--Guinea, 1990. AB - Since December 1989, civil strife in Liberia has caused mass displacement of persons to neighboring Guinea and Ivory Coast (Figure 1). Liberian refugees initially settled in the Forest Region of Guinea and shared food and shelter with members of the same ethnic groups (mainly Gio and Mano) already residing in the area. The number of refugees overwhelmed the capacity of affected villages to provide basic needs, and camp-like settlements were established that received substantial external relief. In May 1990, to determine appropriate priorities for relief assistance, the health and nutritional status of Liberian refugees in the Forest Region of Guinea was assessed by CDC for the U.S. Department of State's Bureau for Refugee Programs. In May, an estimated 80,000 refugees were in the area; by December the number had increased to an estimated 400,000. This report summarizes findings of the health and nutritional assessment of Liberian refugee children. PMID- 1898622 TI - Residential arrangements for adults with cerebral palsy--California, 1988. AB - In the United States, an estimated 274,000 persons have cerebral palsy (CP), a neurologic condition defined as a group of nonprogressive disorders in which an abnormality of the central nervous system can result in motor dysfunction (e.g., paresis, involuntary movement, and incoordination). CP is the third leading cause of the need for assistance with basic life activities and the fifth leading cause of activity limitation. An adult with CP may require adaptive housing to improve accessibility (e.g., to entrances and toilet facilities), attendant care to assist with activities of daily living, and/or nursing care to meet specific health-care needs. These needs can be met through a variety of residential accommodations. However, because the residential environment has a considerable impact on well-being and quality of life, the accommodations should be in the least restrictive environment and, when possible, community-based. This report summarizes an assessment of characteristics of adults with CP to determine which factors are associated with placement in a more restrictive environment. PMID- 1898623 TI - A difference in mortality between two strains of jaundiced rats. AB - Homozygous Gunn rats lack bilirubin glucuronyltransferase, become jaundiced, and often develop kernicterus, thus providing a model for neonatal hyperbilirubinemia. Two new, inbred rat strains that carry the Gunn mutation are described. These were developed by breeding the mutant Gunn gene (j) into the RHA/N and ACI/N strains, producing the new lines, which were designated RHA/N-j and ACI/N-j. Liver assay confirmed the absence of transferase activity in jaundiced rats from both of the new strains, but marked differences in mortality between the strains were observed. The mortality of jaundiced RHA/N-j rats through 8 weeks was the same as that of their nonjaundiced littermates (20%). In contrast, mortality of jaundiced ACI/N-j rats was distinctly greater than that of their nonjaundiced littermates (81% vs 34%, P less than .001). Signs of kernicterus such as ataxia were much more frequent in jaundiced ACI/N-j rats than in jaundiced RHA/N-j rats (73% vs 11%, P less than .001). Both strains had comparable albumin concentrations through 8 weeks of age. Serum bilirubin concentrations were also comparable, except for a small but significant difference at 20 days of age (ACI/N-j = 294 mumols/L, RHA/N-j = 248 mumols/L, P less than .01). Similarly, the bilirubin-to-albumin ratios were comparable except for a significantly higher ratio at 20 days of age in the ACI/N-j rats (ACI/N-j = 0.70, RHA/N-j = 0.51, P less than .01). Thus, the RHA/N-j strain is unusual in that the jaundiced animals remain healthy. Conversely, the ACI/N-j animals demonstrate a high incidence of kernicterus with mortality.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1898624 TI - Alpha-ketoglutarate preserves protein synthesis and free glutamine in skeletal muscle after surgery. AB - Serving as a reproducible human trauma model, patients (n = 21) undergoing elective cholecystectomy received postoperative total parenteral nutrition with (n = 9) or without (n = 12) alpha-ketoglutarate (AKG) supplementation. Skeletal muscle biopsy specimens were taken before surgery and on the third postoperative day. The postoperative decreases in the concentrations of free glutamine and basic amino acids seen in the control group were counteracted in the AKG group (p less than 0.05). Muscle protein synthesis was estimated by ribosome analysis. On the third postoperative day the control group showed a decline in the polyribosome concentration (25.8% +/- 4.5%; p less than 0.001). No significant change was observed in the AKG group. On each postoperative day the nitrogen balance was negative in the control group but not in the AKG group. In the control group the cumulative nitrogen balance amounted to -9.9 +/- 1.8 gm of nitrogen and in the AKG group -2.6 +/- 2.6 gm of nitrogen, which was significantly different (p less than 0.05). Administration of AKG, the carbon skeleton corresponding to glutamine, produced results similar to those seen when glutamine is added to postoperative total parental nutrition. The results suggest that the availability of precursors for glutamine synthesis in skeletal muscle is crucial for the degree of muscle protein catabolism after surgical trauma. PMID- 1898626 TI - Radiotherapy of pseudotumors of bone in hemophiliacs with circulating inhibitors to factor VIII. AB - Pseudotumors of bone in two hemophiliacs with severe factor VIII deficiency and a high level of circulating inhibitors are reported. Both had favorable response to radiation therapy after unsuccessful treatment with factor concentrates and remain free of recurrence at 18-62 months. A review of the literature of cases in which radiotherapy has been used is presented. Radiotherapy in the treatment of pseudotumors of bone in hemophiliacs should be strongly considered, particularly if coagulation factor inhibitors are present. PMID- 1898625 TI - Inhibitors of the lipoxygenase pathway specifically block orthopoxvirus replication. AB - Inhibitors of arachidonic acid metabolism, 5,8,11,14-eicosatetraynoic acid (ETYA), BW755c, and nordihydroguaiaretic acid were found to specifically interfere with the replication of cowpox virus (an orthopoxvirus) both in vivo and in vitro. Further studies in vitro showed that the drugs ETYA and BW755c were effective in inhibiting the replication of two additional orthopoxviruses, ectromelia and vaccinia viruses, but not human parainfluenza virus-3. In ETYA treated and cowpox virus-infected cells, early and late gene expression were near normal levels, whereas the assembly of virus-specific membranes was severely reduced. These results are compatible with a model of orthopoxvirus replication that has an obligate requirement for arachidonic acid or one of its metabolic forms, possibly in the assembly of virus-specific membranes. PMID- 1898627 TI - Absence seizures induced by lithium: possible interaction with fluoxetine. PMID- 1898628 TI - Direct costs of emergency medical care: a diagnosis-based case-mix classification system. AB - STUDY OBJECTIVE: To develop a diagnosis-based case mix classification system for emergency department patient visits based on direct costs of care designed for an outpatient setting. DESIGN: Prospective provider time study with collection of financial data from each hospital's accounts receivable system and medical information, including discharge diagnosis, from hospital medical records. SETTING: Three community hospital EDs in Los Angeles County during selected times in 1984. MEASUREMENTS AND MAIN RESULTS: Only direct costs of care were included: health care provider time, ED management and clerical personnel excluding registration, nonlabor ED expense including supplies, and ancillary hospital services. Indirect costs for hospitals and physicians, including depreciation and amortization, debt service, utilities, malpractice insurance, administration, billing, registration, and medical records were not included. Costs were derived by valuing provider time based on a formula using annual income or salary and fringe benefits, productivity and direct care factors, and using hospital direct cost to charge ratios. Physician costs were based on a national study of emergency physician income and excluded practice costs. Patients were classified into one of 216 emergency department groups (EDGs) on the basis of the discharge diagnosis, patient disposition, age, and the presence of a limited number of physician procedures. Total mean direct costs ranged from $23 for follow-up visit to $936 for trauma, admitted, with critical care procedure. The mean total direct costs for the 16,771 nonadmitted patients was $69. Of this, 34% was for ED costs, 45% was for ancillary service costs, and 21% was for physician costs. The mean total direct costs for the 1,955 admitted patients was $259. Of this, 23% was for ED costs, 63% was for ancillary service costs, and 14% was for physician costs. Laboratory and radiographic services accounted for approximately 85% of all ancillary service costs and 38% of total direct costs for nonadmitted patients versus 80% of ancillary service costs and 51% of total direct costs for admitted patients. CONCLUSION: We have developed a diagnosis-based case mix classification system for ED patient visits based on direct costs of care designed for an outpatient setting which, unlike diagnosis-related groups, includes the measurement of time-based cost for physician and nonphysician services. This classification system helps to define direct costs of hospital and physician emergency services by type of patient. PMID- 1898629 TI - Safety and efficacy of oral flecainide therapy in patients with atrioventricular re-entrant tachycardia. AB - OBJECTIVE: To assess the short- and long-term safety and efficacy of oral flecainide therapy in patients with symptomatic tachycardia and an extranodal accessory pathway. DESIGN: Open-label, uncontrolled trial with a mean follow-up of 24 months. SETTING: Referral-based, teaching medical center. PATIENTS: Sixty three patients with symptomatic tachycardia and an extranodal accessory pathway. INTERVENTIONS: Patients had electrophysiologic testing before and after the initiation of oral flecainide therapy and were followed long-term for the presence of symptoms, new physical limitations, and adverse effects of therapy. MEASUREMENTS AND MAIN RESULTS: Flecainide therapy prevented or slowed (324 +/- 59 ms to 398 +/- 55 ms; P less than 0.001) inducible sustained atrioventricular reciprocating tachycardia in 44 of 63 patients (70%). Of the 44 patients discharged from the hospital, 33 (75%) have continued to receive flecainide therapy and have shown no adverse effects (mean follow-up, 24 +/- 10 months). Adverse cardiac reactions (proarrhythmia or sinus node suppression) attributable to flecainide occurred in 11 of 63 patients (17%); in 9 (82%) of these 11 patients, events were detected during either in-hospital monitoring or the electrophysiologic study done before discharge. Structural heart disease was detected by two-dimensional echocardiography in 8 of 11 patients who had adverse cardiac events and in 6 of 52 patients who did not have such events (P less than 0.001). Isoproterenol reversed the effects of flecainide therapy in 11 of 21 patients; 7 of the 11 patients had spontaneous clinical recurrences of tachycardia or palpitations during the follow-up period, but these symptoms occurred in only 1 of 10 patients who did not show isoproterenol-induced reversal (P = 0.02). CONCLUSIONS: Oral flecainide therapy was effective in 33 of 63 patients who had tachycardia and an extranodal accessory connection. Hospital monitoring during initial therapy is recommended, and flecainide should be used with caution, if at all, in patients with structural heart disease. An isoproterenol challenge appears to be helpful in predicting late recurrence of tachycardia. PMID- 1898630 TI - Failure of ciprofloxacin to eradicate convalescent fecal excretion after acute salmonellosis: experience during an outbreak in health care workers. AB - OBJECTIVE: To determine the efficacy of ciprofloxacin therapy in eradicating convalescent fecal excretion of salmonellae after acute salmonellosis. DESIGN: Randomized, placebo-controlled, double-blind trial of ciprofloxacin, with prospective follow-up of nonparticipants. SETTING: An acute care community hospital experiencing an outbreak of salmonellosis. PATIENTS: Twenty-eight health care workers developed acute infection with Salmonella java; 15 participated in a placebo-controlled trial of ciprofloxacin, beginning on day 9 after infection. INTERVENTIONS: Eight patients were randomly assigned to receive ciprofloxacin, 750 mg, and 7 patients to receive placebo; both were administered orally twice daily for 14 days. Nonparticipants who received therapy were placed on the same ciprofloxacin regimen. MEASUREMENTS AND MAIN RESULTS: Study participants had follow-up stool cultures every 3 days initially and then weekly for 3 weeks; nonparticipants were followed until three consecutive cultures were negative. All eight ciprofloxacin recipients showed eradication of S. java from stool cultures within 7 days of beginning therapy (compared with 1 of 7 placebo recipients), and their stool cultures remained negative up to 14 days after discontinuing therapy (P less than 0.01). However, 4 of 8 relapsed; their stool cultures became positive between 14 and 21 days after therapy. In addition, 3 of 3 hospitalized patients treated with ciprofloxacin who did not participate in the controlled trial also relapsed. Thus, the total relapse rate was 7 of 11 (64%; 95% CI, 31% to 89%). In 4 of these 7 patients, relapse was associated with a longer duration of fecal excretion of salmonellae than that of the placebo group. Relapse could not be explained on the basis of noncompliance, development of resistance, or presence of biliary disease. CONCLUSIONS: Despite its excellent antimicrobial activity against salmonellae and its favorable pharmacokinetic profile, ciprofloxacin at a dosage of 750 mg orally twice daily had an unacceptably high failure rate in patients with acute salmonellosis and may have prolonged fecal excretion of salmonellae. The late occurrence of relapses indicates the need to obtain stool cultures up to 21 days after therapy to document fecal eradication in acute salmonellosis. PMID- 1898631 TI - Bupropion reduces cocaine abuse in methadone-maintained patients. PMID- 1898632 TI - T-cell receptor delta gene recombination in common acute lymphoblastic leukemia: preferential usage of V delta 2 and frequent involvement of the J alpha cluster. AB - A high frequency (greater than 80%) of acute lymphoblastic leukemias (ALL) exhibit a recombination of the T-cell receptor (TCR) delta chain locus. Interestingly, distinct TCR delta elements are preferentially used in immunologic subtypes. In a recent series of 201 children with common ALL (cALL) we observed a TCR delta rearrangement in 162 patients, 57% of the latter showing a hybridization pattern in Southern blots suggestive of a V delta 2 to D delta 3 recombination. To verify this interpretation and to elucidate in more detail the diversity of this common type of TCR delta recombination we amplified and sequenced the junctional region of nine cALL patients and cell line REH-6 by polymerase chain reaction (PCR). A V delta 2 D delta 3 recombination was confirmed in all cases; convincing evidence for the participation of D delta 1 or D delta 2 elements was not obtained. Eight of nine patients and REH-6 showed complete 5' D delta 3 boundaries within V delta 2 D delta 3 segments, a limitation of junctional diversity also detected in 50% of peripheral blood cell clones derived from two healthy probands. Notably, sequence identity at the V delta 2 D delta 3 junction was demonstrated for a cALL and one of the control clones. Another group of 35 of 162 cALL patients was characterized by V delta 2 rearrangements and biallelic deletion of J delta and C delta sequences. Using a J alpha consensus primer, PCR-directed sequence analysis demonstrated V delta 2 D delta 3 J alpha recombinations in all four cases analyzed by this approach. The J alpha segments of these patients differed, but were identical or homologous to published J alpha elements. Our data suggest a recombination pathway of the TCR delta/alpha locus leading to chimeric TCR alpha molecules, containing V delta and, remarkably, also D delta sequences. PMID- 1898633 TI - The dyad symmetry element is the molecular target for c-fos induction and inhibition during K 562 differentiation along mutually exclusive lineages. AB - The c-fos proto-oncogene seems to play an important role during differentiation and activation of cells from the hematopoietic lineage. Therefore, it is of interest to investigate the mechanism underlying its transcriptional activation in these cells. To delineate the sequences and factors involved in c-fos transcriptional activation during the course of myeloid cell differentiation, we have used the K 562 chronic leukemic cell line as a model. K 562 cells were transfected with chloramphenicol transacetylase (CAT) reporter constructs, including various regions of the human c-fos promoter, and induced to differentiate by two distinct agents: 12-O-tetradecanoyl phorbol-13-acetate (TPA), which activates a differentiation program along the megakaryoblastic pathway; and hemin, which induces erythroid differentiation. We show here that TPA treatment of K 562 cells induces fos CAT reporter constructs activation, whereas treatment with hemin does not. Furthermore, predifferentiation of the cells with hemin blocks a subsequent induction by TPA, in correlation with the inhibition by hemin of megakaryoblastic differentiation markers appearance. Both the induction by TPA and the inhibition by hemin are mediated by a dyad symmetry element (DSE) located in the upstream regulatory region, between -318 and -296. These results suggest that the protein complex binding to the DSE regulatory element is the target for c-fos activation by TPA and inhibition by hemin in K 562 cells. However, no modulation of protein affinity for the DSE sequence was detected by gel shift assay during the course of induction or inhibition, suggesting that the structural change responsible for the transcriptional modulation is too unstable or too subtle to be detected by this method. PMID- 1898634 TI - Introduction to "Melanomas of Childhood" by Spitz. PMID- 1898635 TI - Melanomas of childhood. 1948. PMID- 1898636 TI - The National Cancer Data Base. PMID- 1898637 TI - Care of the child dying of cancer: Part II. PMID- 1898638 TI - Unproven methods of cancer management. National Health Federation. PMID- 1898639 TI - Preliminary report of the National Cancer Data Base. PMID- 1898640 TI - Flecainide acetate prevents recurrence of symptomatic paroxysmal supraventricular tachycardia. The Flecainide Supraventricular Tachycardia Study Group. AB - Oral flecainide acetate was administered to 34 patients with documented symptomatic paroxysmal supraventricular tachycardia (PSVT) with a double-blind, placebo-controlled, 8-week crossover trial design. PSVT was defined as a regular tachycardia of at least 120 beats/min without evidence of atrioventricular dissociation. The study required considerable patient cooperation. Patients first entered a 4-week qualifying phase followed by a 3-week, open label, flecainide dose-ranging phase. They were then randomized in a blind fashion to receive either placebo or tolerated flecainide dose for an 8-week treatment period and then crossed over after four symptomatic documented episodes of PSVT or at the end of the treatment period. By all efficacy parameters analyzed, flecainide was superior to placebo. Flecainide was associated with an actuarial 79% freedom from symptomatic PSVT events compared with only 15% on placebo at 60 days (p less than 0.001). Of the 34 patients, 29 had recurrence of symptomatic PSVT at least once during the placebo phase; only eight patients had a recurrence during the flecainide phase (p less than 0.001). The median time to the first symptomatic PSVT event was 11 days in the placebo group and greater than 55 days in the flecainide group (p less than 0.001). Likewise, the interval between attacks was a median of 12 days on placebo compared with more than 55 days on flecainide (p less than 0.001). Finally, the flecainide slowed symptomatic PSVT heart rates to 143 +/- 12 beats/min from 178 +/- 12 on placebo (p less than 0.02) in the seven patients who had events in the placebo and flecainide treatment phases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1898641 TI - Racial differences in responses to thrombolytic therapy with recombinant tissue type plasminogen activator. Increased fibrin(ogen)olysis in blacks. The Thrombolysis and Angioplasty in Myocardial Infarction Study Group. AB - To determine whether there are differences in responses to thrombolytic therapy in certain populations, the data for the Thrombolysis and Angioplasty in Myocardial Infarction (phase 1) study were analyzed for black and white patients. Baseline variables including risk factors and extent of coronary artery disease were similar in the 352 white and 24 black patients. The time from onset of chest pain to recombinant tissue-type plasminogen activator (rt-PA) therapy and rt-PA dosing regimens were the same in the two groups. The patency rate of the infarct related artery at 90 minutes was 91% for blacks and was 72% for whites (p = 0.051). Blacks displayed significantly lower nadir fibrinogen levels (0.57 +/- 0.62 versus 1.3 +/- 0.76 g/l, p less than 0.0001), greater delta fibrinogen (baseline-nadir) (2.7 +/- 1.1 versus 1.7 +/- 1.1 g/l, p less than 0.0001), and increased peak levels of fibrin(ogen) degradation products (837 +/- 865 versus 245 +/- 475 micrograms/ml, p less than 0.0001). rt-PA antigen levels tended to be higher in blacks than in whites (2.8 +/- 2.2 versus 2.2 +/- 3.2 micrograms/ml [p = 0.10] at the peak and 1.6 +/- 1.3 versus 0.99 +/- 1.4 micrograms/ml [p = 0.06] at the end of the maintenance infusion). Major clinical outcomes including survival until time of hospital discharge (92% black versus 93% white, p = 0.68) were not significantly different. However, despite undergoing fewer angioplasty procedures (25% versus 46.3%, p = 0.047), blacks received more transfusions (58.8% versus 19.5% were administered greater than or equal to 2 units packed erythrocytes, p = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1898642 TI - Single-beat estimation of the slope of the end-systolic pressure-volume relation in the human left ventricle. AB - This study assessed a new method of estimating the slope (Ees) of the end systolic pressure-volume relation (ESPVR) from a single beat of the human heart. Left ventricular pressure was recorded with a high-fidelity micromanometer in patients with heart disease during left ventriculography. Peak isovolumic pressure at the end-disastolic volume was estimated by a curve-fitting technique from an isovolumic left ventricular pressure curve. The ESPVR line was drawn from the estimated peak isovolumic pressure-volume point tangential to the left upper corner of the pressure-volume loop. The slope of this estimated ESPVR line from single-beat analysis was compared with the slope of the ESPVR line obtained from three pressure-volume loops in 16 patients given angiotensin II or nitroglycerin infusion. The estimated Ees was 5.0 +/- 2.2 mm Hg/ml/m2, and the conventional Ees was 4.9 +/- 2.7 mm Hg/ml/m2. The estimated Ees showed a positive correlation with the conventional Ees (r = 0.91, p less than 0.001, SEE = 1.2 mm Hg/ml/m2). In the other 13 patients, after dobutamine infusion (5 micrograms/kg/min i.v.) the estimated Ees increased significantly from 5.6 +/- 1.4 to 7.4 +/- 2.0 mm Hg/ml/m2 (p less than 0.01). Thus, the estimated Ees approximated the conventional Ees and was sensitive to a positive inotropic intervention. We conclude that this single beat analysis method facilitates assessment of the beat-by-beat ESPVR of the human heart. PMID- 1898643 TI - Flecainide acetate for long-term prevention of paroxysmal supraventricular tachyarrhythmias. PMID- 1898644 TI - Quality of life after bypass surgery for unstable angina. 5-year follow-up results of a Veterans Affairs Cooperative Study. AB - To assess the effect of bypass surgery on outcome from unstable angina, 468 patients were randomized to medical treatment (237 patients) or surgery plus medical treatment (231 patients) and have been followed for comparison of survival, cardiac end points, and quality of life; the latter end point is discussed in the present report. Data were available at 3 and 5 years for 80% and 82% of patients in the medical group, respectively, and 77% and 80% of patients in the surgery group, respectively. At 3 months after randomization to therapy, 79.8% of patients in the surgery group reported subjective improvement, compared with 58% of the medical group, 12.6% of the surgery group reported no change compared with 24.5% of the medical group, and 5.5% of the surgery group reported worsening compared with 24.5% of the medical group (p less than 0.01 by chi 2). Similar data were found for chest pain status, and the benefit to the surgery group remained statistically significant through 5 years of follow-up. Crossover rate to surgery was 43% by 5 years. Treadmill duration was increased in the surgery group compared with the medical group (6.5 +/- 0.25 versus 5.3 +/- 0.25 minutes at 6 months, p less than 0.01), and a significant difference was again demonstrated at 3 and 5 years. A trend toward decreased recurrence of unstable angina was present in the surgery group at 1 year (six of 168 [3.6%] versus 13 of 187 [6.9%] in the medical group, p = 0.158), but the two groups were similar at 3 and 5 years.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1898645 TI - Radiation therapy to prevent heterotopic ossification after cementless total hip arthroplasty. AB - Clinical and roentgenographic observations on a postoperative low-dose radiation of 1000 cGy for prevention of heterotopic ossification in high-risk patients after 48 noncemented total hip arthroplasties demonstrated no overall statistical difference in the Harris hip scores between the treated group (92.2) and the control group (91.0). There was no difference in the incidence of radiolucent lines about the components, and there were no revisions for aseptic loosening in the treated group. The incidence of clinically significant (Brooker Grades III and IV) heterotopic bone formation was lower in the treated group (7%) than in the control group (32%). This difference in the incidence of heterotopic bone formation was statistically significant. Radiation therapy was effective in preventing postoperative heterotopic bone formation in biologically fixed total hip implants. PMID- 1898646 TI - The noninvasive respiratory care unit. Patterns of use and financial implications. AB - Clinical, socioeconomic, and ethical dilemmas have prompted reevaluation of traditional methods of providing intensive care. Six years ago, we established a noninvasive respiratory care unit (NRCU) for selected patients in need of intensive respiratory monitoring and therapy, particularly those requiring prolonged mechanical ventilation. One impetus for the formation of the NRCU was the expectation that it might prove to be a less costly alternative to the intensive care unit (ICU) for selected patients. We reviewed data from all patients admitted to the NRCU from July 1, 1987 through June 30, 1988 to identify characteristics of the patient population and to evaluate potential cost savings. During one year of operation, 136 patients were admitted to the unit, 107 of whom were mechanically ventilated. Overall, hospital costs for these patients exceeded payments by $1,519,477. Losses were greatest for mechanically ventilated patients and those for whom Medicare or Medicaid were the primary payors. Daily costs of care for mechanically ventilated patients were $1,976 lower in the NRCU than in the medical intensive care unit (MICU). We conclude that the NRCU represents a cost-effective approach to the care of substantial numbers of patients requiring specialized respiratory care. PMID- 1898647 TI - Drug-resistant tuberculosis after gastrectomy. Double jeopardy? AB - Although an increased incidence of Mycobacterium tuberculosis infection is found in patients after subtotal gastrectomy, to my knowledge, the potential for gastrectomy to alter the course and outcome of typical mycobacterial disease has not been noted. I report the case of a patient who developed tuberculosis after a Billroth II subtotal gastrectomy, malabsorbed his antibiotics, and subsequently manifested infection with a drug-resistant strain of M tuberculosis. Altered drug pharmacokinetics should be considered as an important metabolic consequence of subtotal gastrectomy. PMID- 1898648 TI - Bronchoscopy with bronchoalveolar lavage in tuberculosis and fungal infections. AB - STUDY OBJECTIVE: To determine the utility of bronchoscopy with bronchoalveolar lavage for diagnosing M tuberculosis and fungal infections. DESIGN: Retrospective review of patients over a six-year period. SETTING: In- and outpatients of one University hospital and affiliated Veterans Administration Medical Center. PATIENTS: Those who were subsequently found to have either M tuberculosis or fungal infections. INTERVENTIONS: Bronchoscopy with bronchoalveolar lavage specimens were compared to prebronchoscopy sputum, when available. Specimens were sent for smear and culture for both acid-fast bacilli and fungi. In the case of lavage, an aliquot also was studied for cellular differential. MEASUREMENTS AND RESULTS: For TB, sputum was smear-positive in 6/47 (34 percent) and culture positive in 24/47 (51 percent), while bronchoscopy was smear positive in 34/50 (68 percent) and culture positive in 46/50 (92 percent). For fungal infections, no sputum was smear-positive and only 1/22 (5 percent) was sputum culture positive, while bronchoscopy was smear-positive in 14/41 (34 percent) and culture positive in 35/41 (85 percent). Bronchoscopy washings and BAL provided complementary specimens. Eighty-three patients had adequate lavages and the cellularity was significantly different from controls (lymphocytes: TB 18 +/- 11.2 percent [mean +/- SD]; fungal: 13 +/- 11.1 percent; controls 6 +/- 3.1 percent; p less than 0.001; neutrophils: TB 9 +/- 11.5 percent; fungal: 6 +/- 9.1 percent controls: 2 +/- 1.5 percent, p less than 0.01); however, there was overlap and no pattern was characteristic for TB or fungal infections. CONCLUSION: Bronchoscopy with BAL is useful in diagnosing tuberculosis and fungal infections. PMID- 1898649 TI - Anti-hepatitis C virus (HCV) antibodies in heart transplant recipients with posttransplantation chronic viral B and non-A, non-B hepatitis. PMID- 1898650 TI - Lactase expression is controlled differently in the jejunum and ileum during development in rats. AB - This study shows the distribution of the messenger RNA for lactase-phlorizin hydrolase during postnatal development and along the longitudinal axis of the rat small intestine. At birth, this messenger RNA was present along the whole length of small intestine, and its concentration remained elevated during the suckling period despite the concomitant decrease in enzyme activity. At weaning, the amount of lactase messenger RNA dropped specifically in the distal ileum. This decrease in lactase messenger RNA was initiated at the ileocecal junction, progressed gradually towards the jejunum, and followed the decrease in lactase activity several days later. Starvation and refeeding were also found to cause modifications of lactase activity and messenger RNA expression that were prominent in the distal part of small intestine. These data support that posttranscriptional and pretranslational levels of regulation are required to define the spatial and temporal expression of lactase in the rat small intestine. PMID- 1898651 TI - NaCl absorption in the rabbit ileum. Effect of acid-base variables. AB - In vivo and in vitro studies suggest that acid-base variables regulate ion transport in the rabbit ileum. The relative importance of these variables on active Na+ and Cl- absorption has not been defined. Isolated, stripped ileal segments were studied under short-circuited conditions in the Ussing flux chamber. Unidirectional 22Na and 36Cl fluxes were measured after changes in bathing solution pH, PCO2, and/or [HCO3-]. When pH was decreased from 7.6 to 7.1, net flux of Na+ increased from 0.1 +/- 0.7 to 2.6 +/- 0.7 mu Eq/cm2 per hour and net flux of Cl- increased from -2.0 +/- 0.9 to 1.3 +/- 0.6 mu Eq/cm2 per hour. These changes were rapid in onset, completely reversible, and accounted for by changes in mucosal-to-serosal fluxes of these ions. They were accompanied by small decreases in short-circuit current, but there were no changes in residual flux. These pH effects were not inhibited by the presence of luminal bumetanide (1 mmol/L), furosemide (1 mmol/L), hydroflumethiazide (1 mmol/L), or 4,4' diisothiocyanostilbene-2,2'-disulfonate (1 mmol/L), or by the carbonic anhydrase inhibitor methazolamide (1 mmol/L). When data from all combinations of acid-base conditions were combined and analyzed by linear regression, pH was the only variable that correlated with mucosal-to-serosal fluxes (r = -0.84) and net flux (r = -0.85) for Na+, mucosal-to-serosal fluxes (r = -0.96) and net flux (r = 0.99) for Cl-, and short-circuit current (r = 0.97). These findings suggest that extracellular pH modulates active Na+ and Cl- absorption in the rabbit ileum. PMID- 1898652 TI - Different hepatobiliary effects of oral and transdermal estradiol in postmenopausal women. AB - Estrogen-replacement therapy is important for the prevention of postmenopausal osteoporosis. However, oral synthetic and conjugated estrogens increase biliary cholesterol saturation index and risk of gallstone disease. To examine whether transdermal estrogen administration could avoid these adverse effects, 17 postmenopausal women were treated with transdermal estradiol (Estraderm TTS; Ciba Geigy, Arnhem, The Netherlands), 100 micrograms/day for 4 weeks, and after 1 month without therapy, with oral estradiol (Progynova; Schering, Weesp, The Netherlands), 2 mg/day for 4 weeks. The increase in the serum estradiol level was much higher during transdermal than oral estradiol administration. On the contrary, the increase in the serum estrone level was much more pronounced during oral treatment. Both modes of treatment led to a similar reduction of urinary calcium excretion. A highly significant decrease in serum phosphate levels was found during transdermal therapy. Biliary cholesterol saturation index did not change during transdermal therapy (mean +/- SEM, 1.25 +/- 0.06 before and 1.22 +/ 0.07 at the end of transdermal therapy; P = NS). A slight increase in cholesterol saturation index that did not reach statistical significance was found during oral therapy (1.28 +/- 0.09 before and 1.36 +/- 0.09 during oral treatment). However, the subgroup of women with strong increases in serum estrone levels during oral estradiol therapy (greater than 0.5 pmol/mL; n = 8) generally had increased biliary cholesterol saturation index, a decrease in relative percentage chenodeoxycholic acid in bile, and increased serum sex hormone-binding globulin levels during oral treatment. Cholesterol monohydrate crystals were never found in duodenal biles during either treatment. This study indicates that transdermal estradiol does not induce lithogenic bile. On the contrary, oral estradiol leads to lithogenic bile in a subgroup of women with strong increases in serum estrone levels during oral treatment. PMID- 1898653 TI - Postheparin plasma diamine oxidase in subjects with celiac disease. PMID- 1898654 TI - Ca2(+)-sensitive binding of thrombospondin to U937 cells is due to the formation of calcium precipitate in the binding medium. AB - Thrombospondin (TSP) binds to U937 monocytic cells in a Ca2(+)-enhancible and EDTA-inhibitable manner (Silverstein, R. L., and R. L. Nachman. 1987. J. Clin. Invest. 79:867-874; Silverstein, R. L., A. S. Asch, and R. L. Nachman. 1989. J. Clin. Invest. 84:546-552). We reproduced the results when RPMI cell culture medium, but not when HBSS was used as binding medium. Addition of 1 mM Ca2+ to RPMI medium increased the binding of TSP to suspended U937 cells more than eightfold; the increase was blocked by EDTA but not by heparin. Further studies showed that addition of 1 mM Ca2+ to RPMI medium resulted in an insoluble precipitate, which did not form when EDTA was present or when 1 mM extra Ca2+ was added to HBSS. TSP bound to the precipitate in a saturable and specific manner. The precipitate enhanced binding of TSP to MG63 osteosarcoma cells in a monolayer binding assay. Enhancement of binding in the monolayer assay was observed for fibronectin and vitronectin as well. Our data indicate that there is not a specific Ca2(+)-dependent TSP receptor on U937 cell surface. Instead, the extra binding enhanced by Ca2+ is due to the formation of insoluble salts in the medium. PMID- 1898655 TI - Lack of HLA class I antigen expression by cultured melanoma cells FO-1 due to a defect in B2m gene expression. AB - The melanoma cell line FO-1 does not express HLA class I antigens and does not acquire them on the cell surface after incubation with IFN-gamma. Immunochemical studies showed that FO-1 cells synthesize HLA class I heavy chain, but do not synthesize beta 2-microglobulin (beta 2-mu). The latter abnormality is associated with lack of beta 2-mu mRNA which remains undetectable in FO-1 cells incubated with IFN-gamma. The defect was identified as a genetic lesion in the B2m gene, since DNA hybridization analysis detected a deletion of the first exon of the 5' flanking region, and of a segment of the first intron of the B2m gene. HLA class I antigen expression was reconstituted on melanoma cells FO-1 after transfection with the wild-type mouse B2m gene, thereby confirming the abnormality of the endogenous B2m gene. The defect identified in FO-1 cells is distinct from that underlying the lack of HLA class I antigen expression by lymphoblastoid cells Daudi, but is remarkably similar to that causing lack of H-2 class I antigen expression by mouse lymphoblastoid cells R1 (TL-). These results suggest that genetic recombination in the 5' region of the B2m gene is a recurrent mechanism in B2m gene defects. In addition to contributing to our understanding of molecular abnormalities in HLA class I antigen expression by melanoma cells, FO-1 cells represent a useful model for analyzing the role of HLA class I antigens in the biology of melanoma cells and in their interaction with cells of the immune system. PMID- 1898656 TI - Purine catabolism in polymorphonuclear neutrophils. Phorbol myristate acetate induced accumulation of adenosine owing to inactivation of extracellularly released adenosine deaminase. AB - Since physiological concentrations (0.1-1 microM) of adenosine influence the functions of human polymorphonuclear neutrophils (PMNs), we investigated the metabolism of adenosine in suspensions of stimulated and unstimulated PMNs. Stimulation with phorbol myristate acetate (PMA, 1 microM), but not by zymosan (0.5 mg/ml) or N-formyl-methionyl-leucyl-phenylalanine (fMLP, 1 microM), provoked an accumulation of endogenous adenosine at a rate of 2.3 +/- 1.0 amol/cell per minute. A similar accumulation was observed with both unstimulated and stimulated PMNs after the addition of deoxycoformycin (dCF, 1-100 microM), an inhibitor of adenosine deaminase. Exogenous adenosine (10 microM) was deaminated at a rate of 9.8 +/- 3.7 amol/cell per minute in control or zymosan or fMLP-stimulated PMN suspensions. This deamination was nearly completely suppressed when the PMNs had been stimulated with PMA. In contrast, the activity of adenosine deaminase in PMN lysates (231 +/- 72 amol/cell per minute) was not modified by PMA stimulation. alpha, beta-Methyleneadenosine 5'-diphosphate (AMPCP, 2.5 mM), an inhibitor of membranous ecto-5'-nucleotidase, profoundly inhibited endogenous adenosine accumulation under all conditions. PMA stimulation also provoked an inactivation of extracellular adenosine deaminase, purine nucleoside phosphorylase, and lactate dehydrogenase in PMN suspensions. We concluded that PMNs, even when not stimulated, continuously produce adenosine by dephosphorylation of extracellularly released adenylates; and that stimulation of PMNs by PMA causes adenosine accumulation owing to the inactivation of adenosine deaminase released by broken cells. PMID- 1898657 TI - A frameshift mutation in the human apolipoprotein A-I gene causes high density lipoprotein deficiency, partial lecithin: cholesterol-acyltransferase deficiency, and corneal opacities. AB - Epidemiologic data of recent years have identified an important role of HDL deficiency in the etiology of atherosclerosis. Biochemical data suggest that some of these deficiencies may be a consequence of defects in the structural genes of HDL apolipoproteins or of plasma enzymes that modify HDL. We analyzed the genetic defect in a 42-yr-old patient suffering from corneal opacities and complete absence of HDL cholesterol but not of coronary artery disease, thus clinically resembling fish eye disease. The observation of an abnormal immunoblot banding pattern of apolipoprotein A-I (apo A-I) and of reduced lecithin: cholesterol acyltransferase (LCAT) activity in plasma led to sequence analysis of the genes for apo A-I and LCAT in this patient and his family. Direct sequencing of polymerase chain reaction amplified DNA segments containing the exons of the candidate genes, resulted in the identification of a frameshift mutation in apo A I while the LCAT sequence was identical to the wild type. The apo A-I mutation was predictive for an extensive alteration of the COOH-terminal sequence of the encoded protein. Evidence for the release of this mutant protein into the plasma compartment and for the absence of normal apo A-I was derived from ultraviolet laser desorption/ionization mass spectrometry analysis. Our results suggest that a defective apo A-I is the causative defect in this case of HDL deficiency with corneal opacities. PMID- 1898658 TI - The omega/lambda 5 surrogate immunoglobulin light chain is expressed on the surface of transitional B lymphocytes in murine bone marrow. AB - The membrane immunoglobulin heavy chain (micron) plays a feedback role during the pre-B stage of B lymphocyte differentiation. In pre-B cell lines, micron associates with two surrogate light chain proteins. The omega chain is disulfide linked to mu and was predicted to be the product of the lambda 5 gene. The iota chain is noncovalently associated with micron. We demonstrate that the omega protein is indeed the product of the lambda 5 gene and that mu, omega, and iota are coassociated in the same complex. Antibodies against the omega/lambda 5 protein demonstrate the existence of a subpopulation of "transitional" bone marrow B cells that express micron and omega on the cell surface. The majority of these cells also express surface kappa light chains, indicating that in B lymphoid ontogeny the lambda 5 gene is inactivated after the onset of kappa light chain expression. PMID- 1898659 TI - Inducibility of class II major histocompatibility complex antigens by interferon gamma is associated with reduced tumorigenicity in C3H mouse fibroblasts transformed by v-Ki-ras. AB - Paired lines of C3H mouse fibroblasts transformed with murine sarcoma virus (Kirsten strain) were prepared that express high or low levels of class II major histocompatibility complex antigen after treatment with interferon gamma (IFN gamma). Here, we described a comparison of the tumorigenicity of these lines in euthymic syngeneic and thymus-deficient nu/nu mice and in mice depleted of IFN gamma. The class II-inducible cells are clearly less tumorigenic than the noninducible cells in syngeneic mice, but of similar tumorigenicity in nu/nu mice and in mice treated with antibodies to deplete IFN-gamma. We propose that in this system, IFN-gamma induction of class II antigens on the tumor cell surface operates to limit tumor growth; ras expression, which inhibits induction of class II antigens, prevents this and so allows tumor growth. PMID- 1898660 TI - Histologic transformation of follicular lymphoma to diffuse lymphoma represents tumor progression by a single malignant B cell. AB - To investigate the clonal relationship between follicular lymphoma (FL) and transformed diffuse lymphoma (tDL), we examined the expression of tumor idiotype, immunoglobulin (Ig) gene rearrangements and sequence of Ig variable genes in paired tissue specimens. All 16 cases analyzed expressed surface immunoglobulin (sIg) on both the FL and the tDL, though the immunophenotype of one case of FL could not be definitively determined. In 14 of 15 cases, the surface immunophenotype was preserved; the exception was likely secondary to a class switch from IgM to IgG. In 12 of 13 cases, antiidiotypic monoclonal antibodies prepared against the FL reacted with the paired tDL. Analysis of Ig gene rearrangements in four cases by Southern blot hybridization showed evidence of clonal relationships in all cases though concordance was not seen with all probes tested (C kappa, C lambda, JH, PFL1, and PFL2). In the one case that had a discordant L chain rearrangement, sequence analysis of the L chain demonstrated a common mature B cell origin for both the FL and tDL. To determine whether tDL arose from one or more FL cells, the sequences of the H chain variable genes were analyzed. Individual clones of the V region gene of the FL showed a random distribution of changes throughout the sequence. In contrast, individual clones of the V region gene from tDL shared numerous nonrandom sequence alterations, implying a common single cell origin. In conclusion, tDL is a mature B cell and arises by transformation of a single FL cell. PMID- 1898661 TI - Immune recognition of HLA molecules downmodulates CD8 expression on cytotoxic T lymphocytes. AB - An HLA-A2+ cytotoxic T lymphocyte (CTL) line restricted by HLA-A2 in recognition of an influenza B virus nucleoprotein (BNP) peptide uses the CD8 coreceptor in the recognition of this viral peptide. Incubation of these CTL with BNP peptide in the absence of antigen-presenting cells downmodulates CD8 alpha and CD8 beta expression and reduces their ability to lyse target cells without inducing self lysis. CD8 downmodulation was dependent on peptide concentration, time of exposure, and T cell receptor specificity. Another viral peptide from the influenza A virus matrix protein interacting with HLA-A2 had no effect on CD8 expression. Upon further investigation, an anti-HLA class I monoclonal antibody (mAb), anti-HLA class II mAb, and HLA alloantisera were found to downmodulate CD8 alpha and CD8 beta expression and induce CTL nonresponsiveness without causing degranulation. When CD8 alpha and CD8 beta expression was modulated by viral peptide or anti-HLA mAbs, other cell surface molecules were unchanged. Finally, incubation of peripheral blood lymphocytes with these anti-HLA mAbs induced no change in CD8 expression on resting cells but did downmodulate it on mitogen activated cells. These results suggest that T cell recognition of the HLA-A2-BNP peptide complex on neighboring CTL may be the mechanism for CD8 downmodulation induced by the BNP viral peptide. This mechanism may be important in clonal anergy. PMID- 1898662 TI - Cytoskeletal function in CD8- and T cell receptor-mediated interaction of cytotoxic T lymphocytes with class I protein. AB - Cloned allospecific cytolytic T lymphocytes (CTL) adhere to purified class I alloantigen immobilized on plastic and degranulate in response to it. Binding and degranulation are inhibited by drugs that impair cytoskeletal function. Cytochalasins D and E, which interfere with microfilament function, and colchicine, which disrupts microtubules, were used and gave qualitatively similar results. Concentrations of these drugs that inhibited degranulation in response to alloantigen did not inhibit response to immobilized anti-T cell receptor (TCR) antibody. Neither did they inhibit response when alloantigen was co-immobilized with an antibody against class I on the CTL to promote adhesion between the CTL and antigen-bearing surface. Thus, neither transmembrane signal generation via the TCR nor degranulation per se were prevented. Instead, the drugs act to prevent the initial adhesion to alloantigen. CTL binding to alloantigen depends in part on CD8-class I interaction, and adhesion via CD8 is "activated" by crosslinking the TCR with soluble anti-TCR antibody. This adhesion, too, is shown to be cytoskeleton dependent. PMID- 1898663 TI - Differentiation of T cell lymphokine gene expression: the in vitro acquisition of T cell memory. AB - A simple in vitro experimental system was devised to reflect the in vivo generation of a T cell anamnestic response so that T cell differentiation could be examined at the level of lymphokine gene expression. Comparison of neonatal and adult T cells revealed that both populations expressed the genes for interleukin 2 (IL-2) and its receptor, but only adult T cells were capable of transcribing mRNAs for IL-3, IL-4, IL-5, IL-6, interferon gamma, and granulocyte/macrophage colony-stimulating factor. However, neonatal T cells could be induced to undergo functional differentiation in vitro, thereby acquiring the capacity to express the lymphokine gene repertoire characteristic for adult T cells. These data suggest that the T cells generated from neonatal blood by a primary stimulation in vitro are functionally indistinguishable from the T cells in adult blood that presumably have undergone primary stimulation in vivo. Therefore, we propose that the term "memory cell" be applied to those T cells that can be identified by their differentiated state of inducible effector lymphokine gene expression. PMID- 1898665 TI - Expression and modulation of HLA-DR on cultured human adult astrocytes. AB - Expression of Class II major histocompatibility complex (MHC) antigens on astrocytes has been implicated as contributing to the immune responses characteristic of chronic autoimmune diseases of the central nervous system. We examined the properties and regulation of HLA-DR on cultured human adult astrocytes. We found that a proportion of human astrocytes from each of fifteen individual donors expressed HLA-DR under basal culture condition; while this proportion differed among the human subjects (range 3-65%), the results for each individual remained relatively constant when analyzed at several time points (up to 125 days in vitro). Attempts to modulate HLA-DR expression by a variety of cytokines likely to be present in inflammatory infiltrates in the brain showed that only gamma-interferon could increase the proportion of human astrocytes that expressed HLA-DR. Whether the variability of HLA-DR expression on astrocytes between different individuals reflects a genetic trait which can influence susceptibility to autoimmune central nervous system diseases remains to be determined. PMID- 1898664 TI - Human platelet-mediated cytotoxicity against Toxoplasma gondii: role of thromboxane. AB - Human platelets, in the absence of antibody, are cytotoxic to tachyzoites of Toxoplasma gondii as determined by vital staining, transmission electron microscopy, and the failure of Toxoplasma to survive and replicate in mice after in vitro interaction of the organisms with platelets. Platelet to T. gondii ratios as low as 1:3 were toxic to the organisms with direct cell-cell contact essential for platelet-mediated cytotoxicity. Adherence of platelets to T. gondii and disruption of surface membranes and cytoplasmic contents of the organisms were observed ultrastructurally. Reactive oxygen species were not implicated in the platelet-mediated toxicity. The interaction of T. gondii with platelets resulted in a marked increase in thromboxane B2 (TXB2) production compared with that by unstimulated platelets. The cyclooxygenase inhibitors acetylsalicylic acid and indomethacin inhibited platelet-mediated cytolytic activity as did the selective TXA2 synthetase inhibitor dazmegrel, indicating a role for thromboxane in the platelet-induced cytotoxicity. Further, toxoplasmacidal activity was retained in the TXA2 synthetase-containing microsomal fractions of platelets disrupted by freezing and thawing; cytolytic activity was absent in microsome depleted platelet supernatant fractions. Both the TXA2-generating platelet microsome system and a stable TXA2 analogue induced damage to the cellular membranes of the Toxoplasma as noted by transmission electron microscopy. These findings suggest that platelets may play a role in the host defense against Toxoplasma and that release of thromboxane may be important in this cytolytic process. PMID- 1898666 TI - Protective cellular retroviral immunity requires both CD4+ and CD8+ immune T cells. AB - We have found previously that postexposure chemoprophylaxis with 3'-azido-3' deoxythymidine (also known as zidovudine or AZT) in combination with recombinant human alpha A/D interferon fully protected mice exposed to a lethal dose of Rauscher murine leukemia virus (RLV) against viremia and disease. After cessation of therapy, over 90% of these mice were able to resist rechallenge with live RLV, thus demonstrating an acquired immunity. Adoptive cell transfer of 4 x 10(7) cells from immunized mice fully protected naive recipients from viremia and splenomegaly after RLV challenge. However, when these immune T cells were fractionated into CD4+ and CD8+ subpopulations, only partial protection was found when 4 x 10(7) T cells of either subset were given. Full protection against RLV challenge was seen again when the T-cell subsets from immunized mice were recombined and transferred at the same number into naive mice. We conclude that cellular immunity alone is protective and that both CD4+ and CD8+ cell types are required for conferring full protection against live virus challenge. PMID- 1898667 TI - The Rex proteins of human T-cell leukemia virus type II differ by serine phosphorylation. AB - The Rex proteins of human T-cell leukemia virus types I and II (HTLV-I and HTLV II) induce cytoplasmic expression of unspliced gag-pol mRNA and singly spliced env mRNA and are critical for virus replication. Two rex gene products, p27rex and p21rex of HTLV-I and p26rex and p24rex of HTLV-II, have been detected in HTLV infected cells; however, the structural and biological relationship of the proteins has not been clearly elucidated. Endoproteinase digestion and phosphoamino acid analysis of HTLV-II Rex indicated that p24rex has the same amino acid backbone as p26rex and that the larger apparent molecular size of p26rex is attributable to serine phosphorylation. PMID- 1898668 TI - Update--transmission of HIV infection during an invasive dental procedure- Florida. AB - Possible transmission of human immunodeficiency virus (HIV) infection during an invasive dental procedure was previously reported in a young woman (patient A) with acquired immunodeficiency syndrome (AIDS). Patient A had no identified risk factor for HIV infection and was infected with a strain of HIV closely related to that of her dentist as determined by viral DNA sequencing. A follow-up investigation has identified four additional patients of the dentist who are infected with HIV. Laboratory and epidemiologic investigation has been completed on three of these patients; two are infected with strains closely related to those of the dentist and patient A but not to strains from other persons residing in the same geographic area as the dental practice. The follow-up investigation included review of medical records of the dentist and interviews of former staff on the infection-control procedures of the dental practice. This report summarizes the findings of the investigation. PMID- 1898669 TI - Tornado disaster--Illinois, 1990. AB - On August 28, 1990, from 3:15 to 3:45 p.m., the strongest tornado in northern Illinois in greater than 20 years struck the towns of Plainfield, Crest Hill, and Joliet in Will County. As a result of the storm's impact phase, 302 persons were injured (28 fatally). This report summarizes an investigation of injuries and deaths that resulted from the tornado's impact. PMID- 1898670 TI - Measles vaccination levels among selected groups of preschool-aged children- United States. AB - In 1989 and 1990, the incidence of measles increased dramatically among preschool aged children in inner cities. The largest outbreaks occurred primarily among unvaccinated black and Hispanic children in large cities (e.g., Chicago [2], Dallas, Houston, Los Angeles, Milwaukee, and New York). However, measles outbreaks have not occurred in all large U.S. cities; differences in vaccine coverage could account for these variations. This report describes surveys of vaccination levels among nonrandomly selected first- and fifth-grade students in Boston, part of New York City (Bronx), Cleveland, Houston, Jersey City, Philadelphia, Pittsburgh, and Seattle. PMID- 1898671 TI - A novel testis-stimulating factor in familial male precocious puberty. AB - BACKGROUND: Familial male precocious puberty is a gonadotropin-independent form of precocious puberty that occurs only in males. The cause of the disorder is unknown. To examine the hypothesis that the plasma of boys with familial male precocious puberty contains a novel stimulator of testicular testosterone production, we developed a bioassay using adult male cynomolgus monkeys. METHODS: We collected plasma from 12 boys with familial male precocious puberty, 7 normal prepubertal boys of similar ages and with similar plasma gonadotropin levels, and 1 boy with hypogonadotropic hypogonadism and infused it into the testicular artery of adult male cynomolgus monkeys that had been pretreated with gonadotropin-releasing-hormone antagonist to inhibit the endogenous secretion of gonadotropins. Testicular venous effluent was collected at 15-minute intervals for 3 or 5 hours for the measurement of testosterone. RESULTS: The mean (+/- SE) peak testosterone response, as compared with base line, was significantly greater in the monkeys infused with plasma from the 12 boys with familial male precocious puberty than in the monkeys infused with plasma from the 7 normal prepubertal boys and the boy with hypogonadotropic hypogonadism (385 +/- 51 vs. 184 +/- 25 percent, P less than 0.005) in the three-hour studies. Plasma from 92 percent of the boys with familial male precocious puberty and 12.5 percent of the normal prepubertal boys stimulated a response greater than 195 percent of base-line values. In the animals studied for five hours after receiving a second dose of antagonist, the mean peak testosterone response, as compared with base line, was significantly greater in the monkeys infused with plasma from three boys with familial male precocious puberty than in the monkeys infused with plasma from three normal prepubertal boys (363 +/- 81 vs. 115 +/- 6 percent, P less than 0.01). The mean area under the testosterone-response curve was significantly larger in the monkeys infused with plasma from the boys with familial male precocious puberty in the five-hour studies (154 +/- 34 vs. -58 +/- 10 percent, P less than 0.005), but not in the three-hour studies. CONCLUSIONS: These findings support the presence of a circulating testis-stimulating factor in the plasma of boys with familial male precocious puberty. The production of such a factor would explain the biologic nature of the disorder. PMID- 1898672 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 4-1991. An 18-year-old man with Morquio's syndrome and a tumor of the right femur. PMID- 1898673 TI - More on Silver Spring monkeys. PMID- 1898674 TI - Activation by adrenaline of a low-conductance G protein-dependent K+ channel in mouse pancreatic B cells. AB - Insulin is produced and secreted by the B cells in the endocrine pancreas. In vivo, insulin secretion is under the control of a number of metabolic, neural and hormonal substances. It is now clear that stimulation of insulin release by fuel secretagogues, such as glucose, involves the closure of K+ channels that are sensitive to the intracellular ATP concentration (KATP channels). This leads to membrane depolarization and the generation of Ca2(+)-dependent action potentials. The mechanisms whereby hormones and neurotransmitters such as adrenaline, galanin and somatostatin, which are released by intraislet nerve endings and the pancreatic D cells, produce inhibition of insulin secretion are not clear. Here we show that adrenaline suppresses B-cell electrical activity (and thus insulin secretion) by a G protein-dependent mechanism, which culminates in the activation of a sulphonylurea-insensitive low-conductance K+ channel distinct from the KATP channel. PMID- 1898675 TI - Neopterin and interferon-gamma in serum and cerebrospinal fluid of patients with HIV-associated neurologic disease. AB - We measured the levels of interferon-gamma (IFN-gamma) and neopterin in the serum and cerebrospinal fluid of 121 human immunodeficiency virus-seropositive (HIV+) and 62-seronegative (HIV-) individuals evaluated for neurologic disease. CSF levels of IFN-gamma and serum and CSF levels of neopterin were higher in HIV+ than in HIV- individuals. Patients with HIV- related meningitis and with opportunistic CNS infections had higher serum neopterin levels than HIV+ asymptomatic individuals. CSF levels of IFN-gamma were slightly higher in CSF of HIV+ individuals in all groups (0.31 +/- 0.03 U/ml) than in HIV- individuals (0.12 +/- 0.03). CSF levels of neopterin were similar in HIV+ asymptomatic individuals (6.9 +/- 0.7 nmol/l) and HIV- individuals (5.9 +/- 1.1), but were elevated in those HIV-infected individuals with neurologic disease, particularly patients with HIV-associated meningitis (72.1 +/- 13.3 nmol/l), opportunistic CNS infections (36 +/- 9.1), and inflammatory demyelinating polyneuropathies (32.4 +/ 17.2). Levels of neopterin correlated positively with levels of soluble interleukin 2 receptor and soluble CD8, 2 additional indicators of immune activation. In the absence of neurologic disease, levels of IFN-gamma and neopterin in both serum and CSF were stable for up to 4 years after seroconversion. These data suggest that increased CSF neopterin is associated with HIV-associated neurologic disease. PMID- 1898676 TI - Ankle sprains are always more than 'just a sprain'. AB - When your patient sprains an ankle, you know what to do. The diagnosis is not difficult, treatment is minimal, and the prognosis is excellent--right? Not always. Reading Dr Stanley's article will help you diagnose, treat, and rehabilitate with confidence. PMID- 1898677 TI - A practical guide to nitrate use. AB - Nitrate preparations are useful in the treatment of acute and chronic angina, acute and chronic congestive heart failure, and acute myocardial infarction. Development of tolerance is best managed by providing a nitrate-free interval, thus avoiding continuous drug levels. This interval probably should be 10 to 12 hours with use of a transdermal patch. Nitrate treatment of the elderly may require lower doses to avoid hypotension. PMID- 1898678 TI - Prehospital diagnosis and treatment of acute myocardial infarction: a north-south perspective. The Cincinnati Heart Project and the Nashville Prehospital TPA Trial. AB - Intravenous thrombolytic therapy improves left ventricular function and reduces mortality in patients with acute myocardial infarction (AMI). In European and Middle Eastern trials, prehospital delivery of thrombolytic agents by physician directed mobile intensive care units has been successful. This report describes two independently conceived and performed trials that used cellular telephone transmission of 12-lead ECGs to deliver recombinant tissue plasminogen activator (r-tPA) in the field to patients with AMI. In the Nashville Prehospital TPA Trial, 85 patients with chest pain were evaluated in the field for possible administration of r-tPA over a 6-month period. Three of 85 patients (3.5%) were found to be actual candidates for r-tPA treatment in the field. In phase II (dry run phase) of the Cincinnati Heart Project, 374 patients were evaluated in the field with 14 documented cases of AMI (3.7%) before r-tPA was placed in ambulances for administration by paramedics. In phase III (active with r-TPA in ambulances), over a 1-year period 103 patients were evaluated with six (5.8%) documented cases of AMI. Three of five r-tPA field treatment decisions by emergency physicians using transmitted 12-lead ECGs were accurate (60%). When patients in phases II and III were combined, only 20 of 477 total patients (4.2%) were documented to have AMI. A decline in paramedic skills was noted because of the infrequent administration of the thrombolytic agent. Combining the Nashville and Cincinnati experiences, only 27 of 562 total patients with chest pain (4.8%) were candidates for prehospital thrombolysis. We conclude that few patients evaluated in the prehospital setting are actual candidates for thrombolytic therapy. Substantial allocation of financial and human resources for prehospital delivery of intravenous thrombolytic therapy does not appear warranted. PMID- 1898679 TI - Influence of endothelin on cardiovascular function, oxygen free radicals, and blood chemistry. AB - Endothelin, a peptide that is derived from vascular endothelial cells, is a potent constrictor of mammalian blood vessels in in vitro studies. Various clinical conditions have been reported to be associated with an increase in the blood and tissue levels of endothelin. In the present study, the effects of two doses (2.059 and 4.118 micrograms/kg, intravenously) of endothelin on cardiac function and contractility; blood lactate, gases, and pH levels; blood and cardiac tissue MDA levels; PMN leukocyte chemiluminescence activity; and total WBC and PMN leukocyte counts were investigated in anesthetized dogs. Hemodynamic measurements and collection of blood samples for various biochemical measurements were made before and at various intervals up to 2 hours after endothelin administration. Endothelin in the large dose (4.118 micrograms/kg) produced a prolonged decrease in the indices of cardiac contractility and cardiac function and increases in TSVR, PVR, and mean right atrial pressure. The changes in the hemodynamic parameters with the smaller dose (2.059 micrograms/kg) were similar but of smaller magnitude. Significant decreases in dp/dt at CPIP:PAW and CI and increases in TSVR and PVR were observed with the smaller dose of endothelin. There were decreases in the blood HCO3- and pH levels and an increase in H+ and blood lactate concentration and CK activity with the high dose of endothelin. No changes were observed in blood PO2 and PCO2 with either dose of endothelin. Circulating WBCs and PMN leukocytes decreased significantly with both doses of endothelin. There were no changes in the oxygen free radical-producing activity of PMN leukocytes and in the blood and cardiac tissue MDA levels. These results suggest that endothelin decreased cardiac function and cardiac contractility and increased SVR and PVR. The decrease in cardiac function and contractility may be due to ischemia from constriction of coronary arteries. The hemodynamic changes are unlikely be due to oxygen free radicals since there was no increase in the blood and cardiac tissue MDA levels and no change in the PMN chemiluminescence. These studies suggest that increases in endothelin levels in certain clinical conditions might cause added deleterious effects on cardiovascular function. PMID- 1898680 TI - Recombinant tissue-type plasminogen activator: current concepts and guidelines for clinical use in acute myocardial infarction. Part I. PMID- 1898681 TI - Gallstones in children. Characterization by age, etiology, and outcome. AB - Fifty children and adolescents were found to have gallstones at Children's Hospital of Buffalo (NY) during a period of 10 years. The mean (+/- SD) age was 12.2 +/- 6.2 years, with 21 boys and 29 girls. The majority of patients could be categorized into four groups: hemolytic disease (18 patients), parenteral nutrition (eight patients), adolescent pregnancy (seven patients), and idiopathic (10 patients), while seven patients had a variety of other etiologies. Right upper quadrant pain was the most common symptom (32 patients), followed by jaundice (15 patients), vomiting (13 patients), and nonspecific abdominal complaints (13 patients). Ten patients presented with jaundice and underlying hemolytic disease; seven patients were asymptomatic. Clinical presentation was found to vary with age and factors associated with the development of gallstones. Ultrasonography was the mode of diagnosis in 48 patients. Cholecystectomy was performed in 36 patients. In contrast to gallstones in adults, after exclusion of the patients with adolescent pregnancy, there was no female predominance. Pancreatitis was the most common complication, occurring in 8% of the patients; cholecystitis and cholangitis were absent. PMID- 1898682 TI - The natural history of benign lymphoepithelial lesion of the salivary gland in which there is a monoclonal population of B cells. A report of two cases. AB - In two patients, a diagnosis of benign lymphoepithelial lesion of the salivary gland was followed by the development of extrasalivary gland lymphoma after 10- and 9-year intervals, respectively. On review, immunohistochemistry revealed immunoglobulin light-chain restriction in the initial biopsy in each case and there was both morphological and immunohistochemical evidence linking the extrasalivary gland lymphoma with the initial lesion. It is argued that in the presence of a monoclonal B-cell population, a diagnosis of benign lymphoepithelial lesion is inappropriate. These patients fulfill the criteria for a diagnosis of low-grade B-cell lymphoma of mucosa-associated lymphoid tissue and should be treated accordingly. PMID- 1898683 TI - Hepatic hemangioblastoma. An unusual presentation in a patient with von Hippel Lindau disease. AB - We report a case of multiple capillary hemangioblastomas of the liver occurring in a patient with von Hippel-Lindau disease and a history of previous cerebellar and spinal hemangioblastomas. Although rare examples of this tumor have previously been recorded in the pancreas, kidney, and urinary bladder, this appears to be the first recorded case with hepatic involvement. The histology and immunohistochemical appearance of this neoplasm are identical with those of the cerebellar tumor. We believe it represents a separate primary neoplasm rather than metastatic disease. PMID- 1898684 TI - Prolongation of the QT interval by enflurane, isoflurane, and halothane in humans. AB - Previous investigations in laboratory animals have documented the ability of the volatile anesthetics to prolong the QT interval and the QT interval corrected for level of heart rate, QTc. The purpose of the present investigation was to evaluate the direct electrocardiographic and hemodynamic effects of enflurane, isoflurane, and halothane in healthy, unpremedicated patients using an inhalation induction to avoid the confounding effects of other anesthetic agents. Experiments were conducted in 22 adult male patients, (ASA physical status I or II) divided into three groups given either enflurane (n = 6), isoflurane (n = 8), or halothane (n = 8) anesthesia. Twenty-four-hour preoperative, preinduction, and postinduction hemodynamic and electrocardiographic measurements were obtained. Anesthetic blood concentrations, levels of plasma electrolytes, and arterial blood gas tensions were also quantitated. Halothane administration (0.81 +/- 0.06 mM) did not significantly alter the PR interval or QRS duration but significantly increased the QT (0.38 +/- 0.01 to 0.45 +/- 0.01 s) and QTc intervals (0.39 +/- 0.01 to 0.44 +/- 0.02 s). Isoflurane anesthesia (1.04 +/- 0.11 mM) did not significantly change QRS duration or PR and QT intervals but significantly prolonged the QTc interval (0.42 +/- 0.01 to 0.47 +/- 0.14 s). Similarly, enflurane anesthesia (2.16 +/- 0.13 mM) significantly prolonged the QTc (0.40 +/- 0.01 to 0.46 +/- 0.14 s) without change in QRS duration or PR and QT intervals. Plasma electrolyte levels and arterial gas tensions remained within normal limits in all patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1898685 TI - Masseter muscle spasm in children: implications of continuing the triggering anesthetic. AB - This retrospective study was undertaken to examine the management and outcome of children who developed isolated masseter muscle spasm (MMS) after the administration of intravenous succinylcholine during anesthetic induction. The inhalation anesthetics used for induction were continued in all of these cases. The medical records of 68 patients (male/female ratio, 1.7:1), identified from approximately 42,000 anesthetics given during the period 1980-1989, were reviewed. Fifty-seven children (2.3-12 yr old) were diagnosed as having isolated MMS, i.e., MMS without spasm of other muscles; 11 experienced generalized rigidity in combination with MMS. Anesthetic and postoperative management of these two groups differed. The overall incidence of MMS was 0.3% of inhalation anesthetics during which succinylcholine was given. Intraoperative arrhythmias occurred in 33% of the patients who developed isolated MMS and more frequently in older children. Most children experienced some degree of hypercarbia and/or metabolic acidosis, but the significance of these abnormalities in the spontaneously ventilating, fasting child is unknown. Serum creatine kinase levels when measured 18-24 h postoperatively were elevated in all but one child (n = 45). There was no long-term morbidity and no mortality. We conclude that failure of the masseter muscles to relax after succinylcholine is not uncommon in children. Based on our experience, and accepting that MMS may be part of the clinical spectrum of malignant hyperthermia, we believe that anesthesia can be continued safely in cases of isolated MMS when careful monitoring accompanies diagnostic evaluation. This differs from the current practice of discontinuing the anesthetic or switching to a nontriggering anesthetic technique. PMID- 1898687 TI - Respiratory effects of spinal anesthesia: resting ventilation and single-breath CO2 response. AB - The effects of spinal anesthesia with bupivacaine or lidocaine on resting pulmonary ventilation and on the response to the single-breath carbon dioxide test were studied in 11 unpremedicated patients. Resting end-tidal PCO2 decreased from 34.8 +/- 4.5 (mean +/- SD) to 31.6 +/- 4.6 mm Hg after induction of spinal anesthesia (P = 0.002). The decrease in end-tidal PCO2 correlated negatively with patient age (r = -0.67, P = 0.02) and positively with spinal analgesic level (r = 0.58, P = 0.06). Breath-to-breath variability of ventilation increased during spinal anesthesia. Spinal anesthesia was not associated with statistically significant changes in tidal volume, respiratory rate, minute ventilation, mean inspiratory flow rate, inspiratory duty cycle duration, or the response to the single-breath CO2 test. PMID- 1898686 TI - Cerebral blood flow decreases with time whereas cerebral oxygen consumption remains stable during hypothermic cardiopulmonary bypass in humans. AB - Recent investigations demonstrate that cerebral blood flow (CBF) progressively declines during hypothermic, nonpulsatile cardiopulmonary bypass (CPB). If CBF declines because of brain cooling, the cerebral metabolic rate for oxygen (CMRO2) should decline in parallel with the reduction in CBF. Therefore we studied the response of CBF, the cerebral arteriovenous oxygen content difference (A VDcereO2) and CMRO2 as a function of the duration of CPB in humans. To do this, we compared the cerebrovascular response to changes in the PaCO2. Because sequential CBF measurements using xenon 133 (133Xe) clearance must be separated by 15-25 min, we hypothesized that a time-dependent decline in CBF would accentuate the CBF reduction caused by a decrease in PaCO2, but would blunt the CBF increase associated with a rise in PaCO2. We measured CBF in 25 patients and calculated the cerebral arteriovenous oxygen content difference using radial arterial and jugular venous bulb blood samples. Patients were randomly assigned to management within either a lower (32-48 mm Hg) or higher (50-71 mm Hg) range of PaCO2 uncorrected for temperature. Each patient underwent two randomly ordered sets of measurements, one at a lower PaCO2 and the other at a higher PaCO2 within the respective ranges. Cerebrovascular responsiveness to changes in PaCO2 was calculated as specific reactivity (SR), the change in CBF divided by the change in PaCO2, expressed in mL.100 g-1.min-1.mm Hg-1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1898688 TI - Cardiovascular, respiratory, and analgesic effects of fentanyl in unanesthetized rhesus monkeys. AB - To determine the suitability of the rhesus monkey as a model for investigation of opioids, we examined the analgesic, respiratory, and cardiovascular effects of fentanyl in six adult male rhesus monkeys. Fentanyl was administered in sequential bolus injections of 2, 4, 16, 64, and 128 micrograms/kg, with 10 min between each dose. Arterial plasma fentanyl concentrations and blood gas tensions were measured 3 and 9 min after each dose and 1, 2, 5, 20, 60, and 120 min after the final dose. At the same time periods, mean systemic arterial, pulmonary arterial, central venous, and pulmonary capillary wedge pressures, cardiac output, heart rate, and respiratory rate were measured. Analgesia was quantified as the time required for tail withdrawal from a standardized noxious stimulus. Tail latency response time increased significantly after the 4-microgram/kg dose (plasma fentanyl concentration = 2.7 +/- 0.9 ng/mL). Maximum tail latency response time was attained after the 64-micrograms/kg dose (43.4 +/- 26.0 ng/mL). Respiratory rate decreased significantly after the 2-microgram/kg dose, and PaCO2 increased significantly after the 4-microgram/kg dose. All animals became apneic, requiring tracheal intubation and controlled ventilation, after the 64 micrograms/kg dose. Also, mean arterial pressure and cardiac output decreased significantly after the 64-micrograms/kg dose. There were no other significant cardiovascular changes. Peak plasma fentanyl concentration after the 128 micrograms/kg dose was 117.0 +/- 49.6 ng/mL. It appears that plasma concentrations of approximately 40 ng/mL are sufficient to reach the full cardiovascular, respiratory, and analgesic effects of fentanyl in the rhesus monkey. Significant respiratory and analgesic effects are evident at concentrations as low as 3 ng/mL.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1898689 TI - Myocardial and systemic hemodynamics during isovolemic hemodilution alone and combined with nitroprusside-induced controlled hypotension. AB - Myocardial and systemic effects of isovolemic hemodilution alone and combined with controlled hypotension induced with sodium nitroprusside (SNP) were studied in halothane-anesthetized, open-chest dogs. Regional blood flow was measured with radioactive microspheres and used to compute regional oxygen (O2) supply. Values for regional blood flow in myocardium were used to compute myocardial O2 (MVO2) and lactate uptake (MVLAC) using the Fick equation. Hemodilution to hematocrit 50% of baseline increased aortic blood flow and decreased systemic vascular resistance, although other systemic hemodynamic values were not changed. Twofold increases in myocardial blood flow were accompanied by no change in MVO2, MVLAC, or coronary sinus PO2. Hemodilution increased regional blood flow sufficiently in the pancreas, liver, duodenum, skeletal muscle, skin, and brain to preserve O2 supply whereas unchanged blood flow in the spleen and kidney reduced O2 supply. Under hemodilution, 15 min of intravenous SNP sufficient to reduce mean arterial pressure by 50% caused parallel reductions in aortic blood flow, dP/dt max, and left ventricular end-diastolic pressure; systemic vascular resistance was unaffected. Myocardial blood flow and MVO2 decreased proportionally, whereas MVLAC and coronary sinus PO2 did not change. Regional blood flow and O2 supply decreased in the kidney, spleen, liver, and skin. Extending SNP infusion to 60 min increased myocardial blood flow and MVO2, but other hemodynamic values were unchanged. Comparing previous results with adenosine-induced hypotension inferred that coronary vasodilator reserve was greatly reduced at this time. In conclusion, although myocardial O2 supply versus demand balance was well maintained during SNP-induced hypotension under hemodiluted conditions, diminished coronary vasodilator reserve suggests increased vulnerability to ischemia if stresses of augmented cardiac work demand or impaired arterial oxygenation were superimposed. The decrease in O2 supply in the kidney during combined hemodilution and SNP-induced hypotension also warrants concern. These latter findings suggest the need for extensive clinical monitoring when SNP is used for controlled hypotension under hemodiluted conditions. PMID- 1898690 TI - Contemporary management of neurofibromatosis. AB - The neurofibromatoses are two distinct entities with different genetic origins. The phenotypic expressions and required treatments are different. The devastating nature of neurofibromatosis-2 may be more effectively controlled through the application of advanced imaging techniques and contemporary neurotologic procedures. The most common manifestation of neurofibromatosis-2 is that of bilateral acoustic neuromas. The eventual total bilateral sensorineural deafness associated with this condition can be obviated in selected cases if the diagnosis is established early. Follow-up data are reported for three patients in whom hearing was preserved in at least one ear. When removal with hearing preservation is not possible, subtotal tumor removal with decompression of the internal auditory canals may delay progression of hearing loss. A new approach to tumors of the pterygomaxillary fossa that have extended to the middle cranial fossa has been successfully applied and is described. PMID- 1898692 TI - Binding of preformed xenoantibodies to porcine bioprosthetic valves. AB - We have investigated whether preformed antibodies against xenoantigens bind to cellular elements remaining on porcine bioprosthetic valves after various methods of preservation. Fresh porcine valves treated with either acetone, 4% formaldehyde, or 0.625% glutaraldehyde, as well as an unfixed valve, were incubated with antiserum against porcine xenoantigens. This serum was prepared using the affinity purification method with porcine lymphocytes as the target. The valves were stained with secondary fluorescein-conjugated antibody against immunoglobulin M or immunoglobulin G and examined under fluorescent microscopy. Intense binding of immunoglobulin M to the endocardium was observed in the unfixed valve as well as in valves fixed in acetone and formaldehyde. Glutaraldehyde fixation eliminated binding of antibody. Binding was not noted within the connective tissue. No binding of antiimmunoglobulin G was noted on the endocardium of any of the sections. Examination of three glutaraldehyde-treated porcine valves explanted from the aortic position after 10 years in situ showed no immunoglobulin deposition. These results demonstrate the elimination of antigenicity to preformed antibodies in the endocardium and connective tissue of glutaraldehyde-preserved porcine valves. The findings may, in part, explain the poor performance of formaldehyde-preserved bioprosthetic xenograft valves in the past and support the use of glutaraldehyde as a preferred agent for preservation of bioprosthetic endovascular materials. PMID- 1898691 TI - Elevated circulating interleukin-6 is associated with an acute-phase response but reduced fixed hepatic protein synthesis in patients with cancer. AB - It has been suggested that, as part of the inflammatory response to the presence of a tumor, various cytokines are produced and these induce hepatic synthesis of acute-phase proteins (APP). Under these circumstances it is not known what changes occur in the fixed component of hepatic protein synthesis. The aim of this study was to compare circulating interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor (TNF) concentrations and fixed hepatic protein synthesis rates in a group of healthy controls (n = 6) with a group of patients with an established APP response secondary to hepatic metastasis from colorectal cancer (n = 6). Fixed hepatic protein synthesis rates were measured following a primed, constant 20-hour infusion of 15N-glycine. The liver was biopsied at laparotomy. The APP response was assessed by serum C-reactive protein concentration and cytokines were assayed by a combination of immunoassay and bioassay. The patients with advanced cancer and an on-going APP response had elevated circulating IL-6 concentrations (p less than 0.01). Rates of fixed hepatic protein synthesis were 30% lower than those observed in controls (p less than 0.01). These findings demonstrate that in patients with hepatic metastasis, although the synthesis of certain acute-phase export proteins can be increased, fixed protein synthesis is reduced. Whether these changes in the distribution of hepatic protein synthesis are mediated by IL-6 will require further investigation. PMID- 1898693 TI - Role of potassium concentration in cardioplegic solutions in mediating endothelial damage. AB - We studied the effect of potassium concentration in cardioplegic solutions on endothelial function by examining its influence on 5-hydroxytryptamine- (5-HT) and nitroglycerin-induced vasodilation in the isolated rat heart. Forty-eight rat hearts were perfused on a modified Langendorff preparation. After a baseline record of increase in coronary flow induced by 10(-7) M 5-HT and 10 micrograms/mL nitroglycerin, the hearts were perfused for 30 or 60 minutes with either St. Thomas' solution or Bretschneider solution containing 20 mmol/L of potassium or for 30 minutes with either solution containing 30 mmol/L of potassium (n = 8 in each). Initially, 5-HT and nitroglycerin caused a 39.0% +/- 3.3% and 39.7% +/- 2.8% increase in coronary flow, respectively. After 30 or 60 minutes' perfusion with St. Thomas' solution containing 20 mmol/L of potassium, there was little change in the response to 5-HT or nitroglycerin (5-HT, 43.1% +/- 4.1%; nitroglycerin, 38% +/- 3.2%). Similarly, perfusion with Bretschneider solution (20 mmol/L K+) for 30 or 60 minutes did not alter the degree of vasodilation (5 HT, 39.2% +/- 2.9%; nitroglycerin, 38.0% +/- 3.3%). However, perfusion with St. Thomas' solution containing 30 mmol/L of potassium for 30 minutes abolished the endothelial-dependent 5-HT-induced vasodilation (5-HT, -1.6% +/- 1.4%; nitroglycerin, 36.9% +/- 2.2%). Perfusion with Bretschneider solution (30 mmol/L K+) gave similar results (5-HT, -2.1% +/- 1.2%; nitroglycerin, 36.4% +/- 1.7%). We conclude that the concentration of potassium in cardioplegic solutions plays a critical role in causing functional endothelial damage. PMID- 1898695 TI - Renal sonography in asymptomatic persons with spinal cord injury: a cost effectiveness analysis. AB - A prospective study was undertaken to determine the cost effectiveness of the screening ultrasound examination during the annual check-up of persons with spinal cord injury (SCI). Fifty-two patients, who were otherwise free of illness at the time of examination, were questioned for a history of genitourinary (GU) symptoms and evaluated with a plain film KUB, 24-hour creatinine clearance determination, and renal ultrasound. In those 36 patients without histories of GU symptoms, renal ultrasound alone discovered no treatable pathology. Of the 16 patients with histories of GU symptoms, renal ultrasound did show treatable disease in 13%. Effectiveness of the annual SCI follow-up may be maintained in the demonstration of treatable disease by the selective use of renal sonography only in those patients with histories of GU symptoms. PMID- 1898694 TI - Pravastatin vs gemfibrozil in the treatment of primary hypercholesterolemia. The Italian Multicenter Pravastatin Study I. AB - This study compared the efficacy and safety of pravastatin and gemfibrozil in the treatment of primary hypercholesterolemia. Three hundred eighty-five outpatients from 13 lipid clinics in Italy participated in this randomized double-blind study. Patients were assigned to receive either 40 mg once daily of pravastatin or 600 mg of gemfibrozil twice daily after an initial diet lead-in period. After 24 weeks, mean reductions from baseline values of plasma total and low-density lipoprotein cholesterol were, respectively, 23% and 30% with pravastatin and 14% and 17% with gemfibrozil. Significant lipid-lowering effects were noted within 4 weeks. Apolipoprotein B decrease was 21% with pravastatin and 13% with gemfibrozil. A statistically significant increase of high-density lipoprotein cholesterol of 5% was achieved with pravastatin compared with a 13% increase for gemfibrozil. Serum triglyceride values decreased 5% with pravastatin and 37% with gemfibrozil. Familial and polygenic hypercholesterolemic patients were also examined separately. Pravastatin effectiveness in reducing low-density lipoprotein cholesterol was greater by 6% in polygenic than in familial hypercholesterolemic patients. Treatment for 25 patients (eight treated with pravastatin and 17 treated with gemfibrozil) was discontinued during the study. The incidence of clinical symptoms and laboratory alterations was low for both treatment groups. Pravastatin and gemfibrozil were well tolerated, but pravastatin was significantly more effective in reducing total and low-density lipoprotein cholesterol levels in primary (either familial or polygenic) hypercholesterolemias than gemfibrozil. PMID- 1898696 TI - Interferon-gamma reverses bone marrow inhibition following hemorrhagic shock. AB - Hemorrhagic shock has been demonstrated to alter the myelopoietic response to bacterial lipopolysaccharide. Interferon-gamma has been shown to improve the immune response following experimental shock and injury; however, its effect on myelopoiesis is controversial. This study was performed to determine whether treatment with interferon-gamma will improve the bone marrow response to lipopolysaccharide after hemorrhagic shock. Rats subjected to either shock or a sham procedure were allocated into three groups: (1) control rats received no further treatment; (2) lipopolysaccharide-treated rats received saline for 3 days and then were challenged with lipopolysaccharide to stimulate myelopoiesis; and (3) interferon-treated rats received interferon-gamma (7500 U subcutaneously 1 hour after shock and then every day for 3 days) and lipopolysaccharide as in group 2. Serum colony-stimulating factor levels were measured 6 hours and bone marrow white blood cell count and granulocyte-macrophage colony-forming units (CFU-GM) were measured 24 hours following lipopolysaccharide administration. In sham-treated rats, lipopolysaccharide increased CFU-GM 77% compared with controls. In contrast, treatment with lipopolysaccharide decreased CFU-GM 43% following shock. Treatment with interferon-gamma increased CFU-GM in all animals and reversed the decline in CFU-GM seen in shocked lipopolysaccharide-treated animals. Serum colony-stimulating factor levels were unaffected by either shock or interferon-gamma administration. These data demonstrate that interferon-gamma exerts a stimulatory effect on bone marrow following shock and restores the myelopoietic response to lipopolysaccharide. PMID- 1898697 TI - Effect of exogenous growth hormone on whole-body and isolated-limb protein kinetics in burned patients. AB - The effect of growth hormone on protein kinetics was assessed in burned patients during the hyperdynamic phase using N15 lysine and balance data across the leg. Levels of resting energy expenditure and cardiac index were comparably elevated in all patients, but leg blood flow was greater in the patients receiving growth hormone. Growth hormone therapy (0.2 mg/kg per day) significantly stimulated protein synthesis in the whole body and in the studied leg. A hyperinsulinemic clamp, which raised the insulin concentration to more than 1435 pmol/L of blood, caused comparable stimulation of leg protein synthesis in patients not receiving growth hormone, but did not further increase protein synthesis in the growth hormone-treated patients. These results suggest that administration of exogenous growth hormone may limit the peripheral protein wasting in severely injured patients by a mechanism similar to that of insulin. PMID- 1898698 TI - Pathophysiologic glucocorticoid levels and survival of translocating bacteria. AB - Burn wound sepsis in rats results in sustained corticosterone elevations and the prolonged presence of translocated bacteria in the mesenteric lymph nodes (MLNs). To determine if survival of bacteria in the MLNs may be influenced by pathophysiologic corticosterone levels, MLNs were quantitatively analyzed from rats randomized to the following groups: burn wound sepsis (BI); BI with adrenocortical response attenuated by cyclosporine (cyclosporine/BI); or cyclosporine/BI with corticosterone replacement (cyclosporine/BI + P). Although rates of bacterial translocation were similar, corticosterone levels were significantly different among the three groups and correlated with the number of lymphocytes and the number of enteric bacteria present per gram of MLN. Thus, pathophysiologic elevations of corticosterone levels during sepsis may exert an effect that allows survival of translocated bacteria in the MLNs of rats, perhaps due to glucocorticoid-associated alterations in regional immunity. PMID- 1898699 TI - Lipid-free total parenteral nutrition and macrophage function in rats. AB - Certain lipids are immunosuppressive when used for nutritional support, while other lipids and nutritional additives may enhance immunologic function. We hypothesized that total parenteral nutrition (TPN) may be immunosuppressive irrespective of lipids. Twenty-four rats underwent central vein catheterization and received either intravenous saline solution and oral chow or TPN alone. At 7 or 14 days, the animals were killed. Splenic and bone marrow macrophages were isolated and cultured in either M199 medium alone or were stimulated with Escherichia coli lipopolysaccharide. The supernatants were tested for prostaglandin E2 and C3. The splenic prostaglandin E2 levels were significantly higher in the TPN group following lipopolysaccharide stimulation at 7 days but not at 14 days. Administration of TPN to rats, even without lipids, may be immunosuppressive through the release of prostaglandin E2 from splenic macrophages following a septic challenge. This effect appears to be abolished after 14 days of TPN infusion. PMID- 1898701 TI - Survival following severe overdose with mexiletene, nifedipine, and nitroglycerine. AB - Survival following attempted suicide in a 50-year-old man by ingestion of 12.4 g of mexiletine, 620 mg of nifedipine and 50 to 100 tablets of sublingual nitroglycerine 1:150 is reported. Initial presentation was that of mental obtundation, vomiting, tonic-clonic seizure, high-degree atrioventricular block, profound vasodilation and cardiovascular collapse. Treatment consisted of intravenous calcium gluconate and aggressive fluid management. Maintenance of cardiovascular stability required continuous infusion phenylephrine, dopamine and epinephrine. The patient made a full recovery and was medically discharged on the fourth hospital day. This case represents the largest overdose of mexiletine to date to end in patient survival. PMID- 1898700 TI - Comparison of different doses of epinephrine on myocardial perfusion and resuscitation success during cardiopulmonary resuscitation in a pig model. AB - Published results of dose-response effects of adrenergic drugs (epinephrine [E]) vary so much between studies because of differences in animal models and duration of ischemia before drug administration. In this investigation the effects of different doses of E on coronary perfusion pressure (CPP), left ventricular myocardial blood flow (MBF) and resuscitation success were compared during closed chest cardiopulmonary resuscitation (CPR) after a 4-minute period of ventricular fibrillation in 28 pigs. MBF was measured during normal sinus rhythm using tracer microspheres. After 4 minutes of ventricular fibrillation CPR was performed with the use of a pneumatic piston compressor. After 4 minutes of mechanical measures only, the animals were randomly allocated into four groups of seven, receiving 0.015, 0.030, 0.045, and 0.090 mg/kg E intravenously respectively. MBF measurements were started 45 seconds after E administration; hemodynamic measurements after 90 seconds. Four minutes after the first administration, the same E dose was given before defibrillation. The CPP of animals given 0.015, 0.030, 0.045 and 0.090 mg/kg E were as follows: 16.3 +/- 6.1, 25.6 +/- 5.8, 33.2 +/- 8.4 and 30.4 +/- 6.3 mm Hg. The left ventricular MBF values were: 14 +/- 9, 27 +/- 11, 43 +/- 6, 46 +/- 10 mL/min/100 g. The differences between the groups receiving 0.015 and 0.045 mg/kg and between the groups receiving 0.015 mg/kg and 0.090 mg/kg were statistically significant (P less than .05). Resuscitation success was 14.3%, 42.9%, 100% and 86.7% respectively. A significant difference in resuscitation success was found only between 0.015 mg/kg and 0.045 mg/kg E.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1898702 TI - Pseudonormoglycemia in diabetic ketoacidosis with elevated triglycerides. AB - A 24-year-old newly diagnosed male patient with diabetes presented with diabetic ketoacidosis (DKA) (pH 7.16, HCO3 6.0) and extreme hypertriglyceridemia (239.35 mmol/L). The diagnosis of DKA was delayed because of the apparent depression of the true serum glucose (to 11 mmol/L). He was treated with intravenous (IV) insulin and rehydration, which normalized his pH, HCO3, and triglyceride levels. To the authors' knowledge, this is both the highest triglyceride level recorded and the first report of a high triglyceride level as the apparent cause of a factitiously low glucose level. PMID- 1898703 TI - Retropharyngeal space infections in a community hospital. AB - The emergency physician often has to deal with infectious disease emergencies. The authors have seen four cases of retropharyngeal infection of potentially life threatening severity in less than 1 year, all were admitted through the emergency department (ED). Reporting these cases is important to increase awareness among emergency physicians of this classic disease entity. The characteristics of the patients are discussed including initial diagnostic approaches and the use of computed tomography (CT) scanning of the neck and mediastinum. One case of retropharyngeal space infection caused by Neisseria meningitidis serotype W-135 is described. This is the first such reported case. The recommendations are that, in the absence of overt focal infection, a non-surgical approach to the treatment of these patients is indicated. This should include suitable neck roentgenograms, CT scanning, and high-dose, intravenous, beta-lactamase-resistant antibiotics. PMID- 1898705 TI - Regarding the size of Rh proteins. PMID- 1898704 TI - Quinine-induced immune thrombocytopenia associated with hemolytic uremic syndrome: a new clinical entity. AB - Three patients are described who developed severe thrombocytopenia, microangiopathic hemolytic anemia, and acute renal failure after ingestion of quinine. In one patient, the same clinical findings recurred several months later after another exposure to quinine. Serum from one patient contained quinine dependent IgG antibodies reactive with the platelet glycoprotein (GP) Ib/IX complex. In the second and third cases, serum contained IgG and IgM antibodies reactive with both the GP Ib/IX and IIb/IIIa complexes in the presence of quinine. Quinine appears to have induced both immune thrombocytopenia and the hemolytic uremic syndrome (HUS) in these individuals. Findings made in these cases may have implications for the pathogenesis of some forms of HUS. PMID- 1898706 TI - A case report of malignant pleural mesothelioma with long-term disease control after chemotherapy. AB - Long duration of responses to chemotherapy in patients with malignant pleural mesothelioma (MPM) is rare. The authors report a patient with inoperable MPM who achieved complete remission with combination chemotherapy of cyclophosphamide, doxorubicin, and cisplatin. 5-fluorouracil and mitomycin C (FM) induced another remission after recurrence of the tumor. Retreatment with FM after chemotherapy had been stopped for 20 months yielded another continuing response. The overall tumor-control time is more than 4 years. Literature reviews and the authors' results suggest that MPM may be a chemosensitive tumor in some patients. Additional evaluations of CAP, FM, and methotrexate combination regimens in this disease should be considered. PMID- 1898707 TI - Plasma postheparin diamine oxidase in patients with small intestinal lymphoma. AB - Diamine oxidase (DAO) is an enzyme located almost exclusively in villus tip enterocytes. Its plasma activity is enhanced by intravenous heparin which releases the enzymes from small bowel enterocytes into the blood. Plasma postheparin DAO (PHD) values have been shown to be significantly lower in patients with malabsorption and villous atrophy, thus suggesting that PHD reflects the mature enterocytic mass. In this study we have assayed PHD in five patients with small bowel lymphoma (two with immunoproliferative small intestinal disease [IPSID] and three with non-IPSID lymphoma) associated with malabsorption syndrome and small bowel mucosa atrophy. The PHD test was performed at diagnosis, after partial or complete remission induced by chemotherapy, and during the follow-up. The PHD values, very low at diagnosis (0.66 +/- 0.12 U/ml), increased during chemotherapy and reached the normal range (greater than 3.7 U/ml) when complete remission occurred. The PHD values rapidly and consistently decreased whenever the disease relapsed. Our data indicate that in patients with small bowel lymphoma PHD test is a sensitive marker of small bowel mucosa damage and suggest that it could be useful in monitoring the recovery of mucosal lesions induced by chemotherapy. PMID- 1898708 TI - Recurrence after radiotherapy for glottic carcinoma. AB - A series of 478 patients with T1-3N0 glottic carcinoma treated by irradiation is presented. Of these patients, 320 were previously untreated, whereas 158 patients were referred for treatment of a recurrence after receiving radiotherapy elsewhere. The primary recurrence rate in the previously untreated patients was 10%. The rate was higher in T2 and T3 tumors, poorly differentiated tumors, and in patients who were in poor general condition. Over 80% of the recurrent tumors were Stage pT3 or pT4, whereas 12% of total laryngectomy specimens showed necrosis only with no evidence of tumor. The necrosis rate in previously untreated patients was 1% for T1 tumors, 4% for T2 tumors, and 3% for T3 tumors. Of all tumors, 60% were transglottic when they recurred, whereas only 29% were confined to the glottis at recurrence. Histologic diagnosis had a high sensitivity but a low specificity, indicating that a negative histologic report is unreliable. Of patients with a recurrent primary tumor, 13% were untreatable. The 5-year survival after a primary recurrence was 39%, and the main prognostic factors were sex, T stage at recurrence, and time to recurrence. Of patients available for follow-up at 5 years 49% were alive with a larynx, 5% were alive without a larynx, 13% were dead of the original cancer, and 33% had died of other causes. In those suffering a primary recurrence, the commonest cause of death was a subsequent lymph node metastasis, followed in order of frequency by stomal recurrence and recurrence in the pharyngeal remnant. The hospital mortality rate after laryngectomy was 3%, and 30% of patients undergoing laryngectomy developed a pharyngocutaneous fistula. The recurrence rate in lymph nodes was 14% at 5 years, general condition and T stage being the only significant predictors of recurrence. Only 17% of patients had small (N1) nodes by the time the diagnosis of cervical lymph node recurrence was made, and 27% of all patients were unsuitable for treatment. Host, tumor factors, and time to recurrence were not significant predictors of survival after node recurrence. The survival rate 5 years after node recurrence was 16%, and the main cause of death in those who died was uncontrolled disease in the neck. The hospital mortality after salvage neck dissection was 4.7%. PMID- 1898709 TI - Inhibition by a new bisphosphonate (AHBuBP) of bone resorption induced by the MBT 2 tumor of mice. AB - A new bisphosphonate, 4-amino-1-hydroxybuthylidene-1,1-bisphosphonate (AHBuBP), was compared with 3-amino-1-hydroxypropylidene-1,1-bisphosphonate (AHPrBP) and 1 hydroxyethylidene-1,1-bisphosphonate (HEBP) in terms of its effect on tumor induced osteolysis using a bladder tumor in mice (MBT-2). Tumor cells were inoculated subcutaneously (SC) over the calvaria in mice, resulting in a local tumor causing fragmentation of the bone. The tumor-induced osteolysis associated with osteoclasts proliferation was accompanied with reactive new bone formation. This osteolysis was evaluated by measuring the increased area of bone resorption in reduced opacity to radiograph and histologic study. The results showed the following sequence of potency: AHBuBP greater than AHPrBP = HEBP. This inhibition was obtained with no apparent effect on the growth of the MBT-2 tumor. The authors conclude that AHBuBP appears to be an interesting new bisphosphonate with possible clinical application. PMID- 1898710 TI - Testis cancer. Ichthyosis constitutes a significant risk factor. AB - Testis cancer and ichthyosis are both relatively rare diseases. Hence the finding of six individuals with both these conditions in a small population with testicular cancer is highly conspicuous and indicates some kind of connection among such persons. Despite the identical clinical appearances of their ichthyoses, three of the ichthyotic subjects had no measurable activity of the enzyme, steroid sulfatase (STS) in leucocytes, a distinct characteristic of recessive X-linked ichthyosis (RXLI). However, the remaining three subjects had normal STS activity, a strong indicator of autosomal dominant ichthyosis (ADI). The STS activity in patients with testicular cancer who do not have ichthyosis (N = 30) was also within the normal range. The patients with testicular cancer with no skin disease had elevated serum levels of 4-androstenedione (4-AD), follicle stimulating hormone (FSH), and luteinizing hormone (LH) but had reduced levels of estrone and estrone sulfate. The other serum parameters measured did not significantly differ from normal levels. In essence, the hormone levels obtained for the patients with ichthyotic testicular cancer followed the same pattern, although their dehydroepiandrosterone sulfate (DHEAS) and estrone sulfate levels tended to be slightly higher than normal. However, no conspicuous aberrations in any of the parameters examined were observed, and why men with ichthyosis are at high risk for testicular cancer remains an unresolved issue. PMID- 1898711 TI - A recombinant, membrane-acting immunotoxin. AB - The anti-Tac antibody is known to bind to the p55 chain of the human interleukin 2 receptor. An immunotoxin was produced by genetically linking Clostridium perfringens phospholipase C (PLC) to the Fab domain of anti-Tac. For this purpose, the PLC gene, with its own promoter and signal sequence, was fused to the 5' end of the VHCH1 segment of the anti-Tac heavy chain gene. The anti-Tac light chain gene, with an attached bacterial signal sequence, was made part of the same transcriptional unit. Escherichia coli transformed with the construct secreted a recombinant immunotoxin, anti-Tac(Fab)-PLC, in an active form. Anti Tac(Fab)-PLC bound to cells expressing the interleukin 2 receptor and inhibited protein synthesis, with a 50% inhibitory concentration of 0.02 nM (1.8 ng/ml). PMID- 1898712 TI - Hepatic metabolism of 7,12-dimethylbenz(a)anthracene in male, female, and ovariectomized Sprague-Dawley rats. AB - Dimethylbenz(a)anthracene (DMBA) is a potent inducer of mammary tumors in intact female Sprague-Dawley rats, but not in males or ovariectomized females (OVX). Qualitative and quantitative aspects of hepatic metabolism of DMBA were examined in these three groups of rats, using the nonrecirculating perfused liver, to determine whether the production of proximate carcinogenic metabolites of DMBA by the liver differed among these groups in the same manner as does sensitivity to tumor induction. DMBA was infused into the liver at a constant rate for 60 min. Rates of appearance of DMBA and its metabolites were measured in perfusate and bile during the infusion period and the first 60 min thereafter. The maximum rate of appearance of total metabolites in the perfusate, seen at the end of the infusion period, was highest in the intact female [2.6 +/- 0.3 nmol/(g x min)], slightly lower in the OVX [2.3 +/- 0.2 nmol/(g x min)] and significantly lower in the male [1.0 +/- 0.1 nmol/(g x min)]. The rates of appearance of metabolites in the bile showed the same order as those seen in the perfusate. The major metabolites extracted from the perfusate in all three groups were dihydrodiols, hydroxymethyl metabolites, and several unidentified metabolites. The 3,4 dihydrodiol, a proximate carcinogenic metabolite, appeared in the perfusate at higher rates in the intact female and OVX than in the male. Hydrolysis of bile samples showed that glucuronidation was a major pathway in the excretion of DMBA metabolites in bile. High performance liquid chromatographic analysis indicated that hydrolysis of DMBA glucuronides yielded the 7- and 12-hydroxymethyl metabolites and an unidentified metabolite designated X. The major hydrolysis product in the male was 12-hydroxymethyl while X was found to be the major product in the intact female and OVX. Under the conditions of this study, there were differences in the metabolic activation of DMBA by male and female rat liver. Ovariectomy, followed by DMBA perfusion 7 days later, did not result in significant changes in DMBA metabolism relative to the intact female, except for a decreased rate of excretion of metabolites in bile. PMID- 1898713 TI - Metabolism and disposition of bladder carcinogens in rat and guinea pig: possible mechanism of guinea pig resistance to bladder cancer. AB - The metabolism and disposition of N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT) and 2-amino-4-(5-nitro-2-furyl)thiazole (ANFT) were studied in rat and guinea pig. Rat is susceptible whereas guinea pig is resistant to FANFT-induced bladder cancer. Rats and guinea pigs were p.o. administered either 2-[14C]ANFT or 2-[14C]FANFT (100 mg/kg), and 18-h urine and feces were collected. Tissue distribution of radiolabel was determined. In both species, the highest concentrations of radioactivity expressed as nmol/g tissue were observed in the urine and intestines. Urinary metabolites were separated by high-performance liquid chromatography and radioactivity determined by radioanalytical detection. FANFT was not detected in urine from either species under any experimental condition. More ANFT was observed in urine following FANFT than ANFT administration. This deformylation-dependent excretion of FANFT was demonstrated in both species and has been previously described as renal metabolic/excretory coupling. Less ANFT, the carcinogen more proximate than FANFT, is excreted in guinea pigs compared with rats. A unique ANFT metabolite was identified in guinea pig but not rat urine. This metabolite represented 80 and 18% of radioactivity recovered in guinea pig urine following ANFT and FANFT administration, respectively. A metabolite produced by guinea pig liver and kidney microsomes in the presence of uridine-5'-diphosphoglucuronic acid coeluted with this unique metabolite. The urinary metabolite was characterized using hydrolytic enzymes, acid hydrolysis, and mass spectrometry and identified as an ANFT-N-glucuronide. A unique UDP-glucuronosyl-transferase appears to be responsible, at least in part, for the reduced amount of free ANFT excreted by guinea pigs compared with rats. Reduced levels of urinary ANFT observed in guinea pigs may partially explain the resistance of this species to FANFT-induced bladder cancer. PMID- 1898714 TI - Enhanced host cell reactivation of damaged plasmid DNA in HeLa cells resistant to cis-diamminedichloroplatinum(II). AB - Human HeLa cells resistant to cisplatin were established by stepwise selection. The selected cells showed a 15- to 20-fold cisplatin resistance (CPR) at the dose level resulting in 50% inhibition. These cells were cross-resistant to mitomycin C, melphalan, and ethyl methanesulfonate but not to Adriamycin, colchicine, or vinblastine. The expression of cisplatin-damaged plasmid DNA carrying the bacterial chloramphenicol acetyltransferase (CAT) gene after its transfection into CPR cells was enhanced by approximately 3-fold. This did not correlate with the degree of CPR. However, the development of the CPR phenotype paralleled the enhanced CAT activity. The addition of aphidicolin (an inhibitor of DNA alpha polymerase) to CPR cells effectively diminished the enhanced CAT activity and CPR. These studies have identified an enhanced host cell reactivation of the damaged plasmid in the acquisition of CPR, suggesting that DNA repair is a potential mechanism for the development of CPR phenotype in human cells. PMID- 1898715 TI - N-methyl-N-nitrosourea alters thymocyte subset distribution and targets immature CD4-8+ cells for lymphoma development. AB - The majority of N-methyl-N-nitrosourea (MNU)-induced lymphomas in AKR/J mice express a CD4-8+ phenotype. The CD4-8+ subset in normal thymus contains functionally mature medullary cells and immature cycling cells. This study demonstrates that MNU-induced lymphomas correspond to the immature CD4-8+ subset. In addition, specific changes in the distribution of thymocyte subsets defined by CD4 and CD8 expression were observed after MNU treatment. Cortical thinning and selective depletion of immature CD4-8+ and CD4+8+ subsets occur immediately after treatment. In contrast, immature CD4-8- progenitors and mature medullary CD4+8- and CD4-8+ subsets are relatively resistant to cytotoxicity. Normal thymic architecture and subset distribution are restored within 2 weeks after which selective expansion of the immature CD4-8+ subset occurs. The data suggest that MNU induces neoplastic conversion in progenitor cells corresponding to the CD4-8- or immature CD4-8+ stages of thymocyte maturation. PMID- 1898716 TI - Lymphokine-activated killer (LAK) cells: interferon-gamma synergizes with interleukin-2 to induce LAK cytotoxicity in homogeneous leukemic preparations. AB - Lymphokine-activated killer (LAK) cells are generated by the incubation of lymphocytes with high levels of interleukin-2 (IL-2). We report here that interferon-gamma (IFN-gamma) acts synergistically with low levels of IL-2 to promote LAK differentiation in peripheral blood lymphocytes as well as in homogeneous T acute lymphocytic leukemic cells exhibiting LAK precursor reactivity. No augmentation of LAK response was observed with IFN-alpha-2, IFN beta-1, and IFN-beta-2/IL-6. The synergism between IL-2 and IFN-gamma was expressed in the ability of activated lymphocytes to lyse natural killer resistant cell line targets and surgically removed melanoma cells. The augmented LAK response due to IFN-gamma does not reflect up-regulation of the high-affinity IL-2 receptors consisting both of alpha and beta subunits, since expression of the alpha (Tac) subunit on the responding leukemic cells was not increased by IFN gamma. The observed IFN-gamma/IL-2 synergism in the induction of monoclonal LAK precursors suggests that a single precursor cell responds to both IFN-gamma and IL-2 and that different mechanisms underlie the basal IL-2-mediated LAK response and its enhancement by IFN-gamma. PMID- 1898717 TI - [Effectiveness of pravastatin and bezafibrate in primary hypercholesterolemia]. AB - The efficacy and safety of pravastatin and bezafibrate (in retard form) were compared in a randomised double-blind trial comprising 96 patients (48 men, 48 women; mean age 52.5 [20-68] years) with primary hypercholesterolaemia types IIa and IIb. After four weeks' treatment 6 out of 38 patients (400 mg/d bezafibrate) and 27 out of 58 patients (20 mg/d pravastatin) reached a LDL cholesterol level of 190 mg/dl or less. In the other 31 patients of the pravastatin group the dose was raised to 40 mg/d. During the twelve-week course of pravastatin total cholesterol concentration fell from a mean of 364 +/- 75 mg/dl (initial value) to 281 +/- 61 mg/dl (P less than 0.01), while LDL-cholesterol fell from 288 +/- 81 mg/dl to 206 +/- 64 mg/dl (P less than 0.01) and triglyceride concentration from 168 +/- 83 mg/dl to 148 +/- 80 mg/dl (P less than 0.05). During the twelve-week course of treatment with 400 mg bezafibrate total cholesterol concentration fell from a mean of 363 +/- 91 mg/dl to 325 +/- 73 mg/dl (P less than 0.01), LDL cholesterol level fell from 284 +/- 88 mg/dl to 242 +/- 70 mg/dl (P less than 0.01) and the triglyceride concentration from 173 +/- 91 mg/dl to 121 +/- 83 mg/dl (P less than 0.01). HDL cholesterol concentration rose by 9% in the bezafibrate group and by 8.4% in the pravastatin group (P less than 0.05). Except in the case of HDL-cholesterol, the falls were significantly different in the two treatment groups: pravastatin was superior to bezafibrate in terms of the reductions in both total and LDL-cholesterol (P less than 0.01 for each). However, bezafibrate produced a greater fall in serum triglycerides (P less than 0.05). No serious side effects were associated with either drug. PMID- 1898718 TI - Glial contribution to seizure: carbonic anhydrase activity in epileptic mammalian brain. AB - The activity of carbonic anhydrase (CA), a glial enzyme, was measured in the epileptic cortex of audiogenic DBA/2 mice and of cats with a freeze lesion. In mice, the activity increased with age from birth to 24 days, but were always higher in audiogenic mice than in normal C57/BL mice, reflecting species differences. The difference between the two strains increased sharply from 25 to 40 days of age, after the period of maximal audiogenic susceptibility. Acetazolamide, a CA-specific inhibitor, greatly decreased the seizure severity score of DBA/2 mice after a single intraperitoneal (i.p.) administration (150 mg/kg). After 24 days of age, when CA activities were high, the effect of acetazolamide was less important, suggesting that the increased cortical CA activity might reflect a protective mechanism. In cats with a freeze lesion, no significant changes in CA activities were observed in the actively discharging primary and secondary foci as compared with the nonepileptogenic perifocal cortex and the control cortex of sham-operated animals. The results indicate that the cortex of genetically susceptible audiogenic mice has an increased CA activity. The hypothesis of an adaptive glial mechanism, relating to the age-dependent decrease of seizure susceptibility in DBA/2 mice, is postulated. PMID- 1898719 TI - Effect of DN-1417 on photosensitivity and cortically kindled seizure in Senegalese baboons, Papio papio. AB - The effect of DN-1417, a thyrotropin-releasing hormone (TRH) analogue, on photosensitivity and cortically kindled seizures was examined in seven Senegalese baboons (Papio papio). Intravenous (i.v.) administration of 2 mg/kg had no effect on either photosensitivity or cortically kindled seizures. When this agent was administered intracisternally, both the photomyoclonic response and cortically kindled seizures were suppressed for 4-5 days. A study of the transcallosal response also showed a long-lasting attenuation of the early positive wave (P1) amplitude (peak latency, 5-10 ms) elicited by a single stimulus after cisternal injection of DN-1417. These findings are consistent with the assumption that endogenous TRH is involved in suppression of epileptic seizures. PMID- 1898720 TI - Reflex epilepsy induced by calculation using a "Soroban," a Japanese traditional calculator. AB - We report three cases of reflex epilepsy with myoclonic jerks of the right arm and fingers precipitated by calculation using a Soroban. An EEG spike-wave complex with left central prevalence was induced. Various types of stimulation were used to induce epileptic discharges, and a simultaneous mental task requiring a high degree of concentration and complicated and delicate finger movements was necessary to induce the epileptic discharges. Comparison of our cases with previously reported reflex epilepsy induced by higher mental activity led to the assumption that the neural mechanism inducing seizures in our cases is similar to that of writing epilepsy. Valproate was effective in reducing epileptic discharges, and all patients became seizure-free. PMID- 1898721 TI - Partial motor epilepsy with "negative myoclonus". AB - Three children had both nocturnal unilateral motor seizures and daytime ipsilateral "negative myoclonus" which occurred so frequently that it resembled asterixis. Neurophysiologic studies demonstrated lateralized spike discharges that were time-locked to postural lapse in the contralateral outstretched arm. The clinical course was characterized by good seizure control with benzodiazepines. PMID- 1898722 TI - Reactive occipital epileptiform activity: is it benign? AB - Occipital epileptiform activity that is almost continuous and reactive to eye opening has been associated with a childhood epilepsy syndrome and basilar migraine with seizures. An association of these syndromes with a benign course had been disputed. In this study, a retrospective investigation of reactive occipital epileptiform activity (ROEA) was performed to determine the prognostic value of this distinctive EGG pattern. The EEG and hospital record of patients with ROEA were reviewed with an observation period of 6 months to 8 years. The patients were divided into good and poor outcome groups based on response to treatment. Of 33 patients, 12 (36.4%) had complete seizure control; 21 (63.6%) continued to have poorly controlled seizures. Only 3 (9.1%) patients were able to discontinue antiepileptic drugs (AEDs) without seizure recurrence. Analysis of clinical and EEG variables showed that a history of perinatal difficulties, abnormal neurologic findings, and abnormal EEG background activities occur significantly more frequently in the poor outcome group. This study suggests that ROEA is not uniformly associated with a benign course and that other factors are involved in determining prognosis of the epilepsy. PMID- 1898723 TI - Sulfide-induced sulfide-quinone reductase activity in thylakoids of Oscillatoria limnetica. AB - Sulfide-dependent partial electron-transport reactions were studied in thylakoids isolated from cells of the cyanobacterium Oscillatoria limnetica, which had been induced to perform sulfide-driven anoxygenic photosynthesis. It was found that these thylakoids have the capacity to catalyze electron transfer, from sulfide to externally added quinones, in the dark. Assay conditions were developed to measure the reaction either as quinone-dependent sulfide oxidation (colorimetrically) or as sulfide-dependent quinone reduction (by UV dual wavelength spectrophotometry). The main features of this reaction are as follows. (i) It is exclusively catalyzed by thylakoids of sulfide-induced cells. Noninduced thylakoids lack this reaction. (ii) Plastoquinone-1 or -2 are equally good substrates. Ubiquinone-1 and duroquinone yield somewhat slower rates. (iii) The apparent Km for plastoquinone-1 was 32 microM and for sulfide about 4 microM. Maximal rates (at 25 degrees C) were about 75 mumol of quinone reduced per mg of chlorophyll.h. (iv) The reaction was not affected by extensive washes of the membranes. (v) Unlike sulfide-dependent NADP photoreduction activity of these thylakoids, which is sensitive to all the specific inhibitors of the cytochrome b6f complex, the new dark reaction exhibited differential sensitivity to these inhibitors. 2-n-Nonyl-4-hydroxyquinoline-N-oxide was the most potent inhibitor of both light and dark reactions, working at submicromolar concentrations. 5-n Undecyl-6-hydroxy-4,7-dioxobenzothiazole also inhibited the two reactions to a similar extent, but at 10 times higher concentrations than 2-n-nonyl-4 hydroxyquinoline-N-oxide. 2,5-Dibromo-3-methyl-6-isopropyl-p-benzoquinone, 2-iodo 6-isopropyl-3-methyl-2',4,4'-trinitrodiphenyl ether, and stigmatellin had no effect on the dark reaction at concentrations sufficient to fully inhibit the light reaction from sulfide. We propose that the sulfide-induced factor which enables the use of sulfide as the electron donor for anoxygenic photosynthesis in Oscillatria limnetica is a membrane-bound sulfide-quinone reductase. Its site of interaction is suggested to be either the cytochrome b6 (at the Qc quinone binding site or the bH site) or the plastoquinone pool. The analogy to other anoxygenic photosynthetic systems is discussed. PMID- 1898724 TI - Purification and characterization of the glycogen-bound protein phosphatase from rat liver. AB - Glycogen-bound protein phosphatase G from rat liver was transferred from glycogen to beta-cyclodextrin (cycloheptaamylose) linked to Sepharose 6B. After removal of the catalytic subunit and of contaminating proteins with 2 M NaCl, elution with beta-cyclodextrin yielded a single protein on native polyacrylamide gel electrophoresis and two polypeptides (161 and 54 kDa) on sodium dodecyl sulfate polyacrylamide gel electrophoresis. Several lines of evidence indicate that the latter polypeptides are subunits of the protein phosphatase G holoenzyme. First, these polypeptides were also present, together with the catalytic subunit, in the extensively purified holoenzyme. Also, polyclonal antibodies against these polypeptides were able to bind the holoenzyme. Further, while bound to cyclodextrin-Sepharose, the polypeptides were able to recombine with separately purified type-1 (AMD) catalytic subunit, but not with type-2A (PCS) catalytic subunit. The characteristics of the reconstituted enzyme resembled those of the nonpurified protein phosphatase G. At low dilutions, the spontaneous phosphorylase phosphatase activity of the reconstituted enzyme was about 10 times lower than that of the catalytic subunit, but it was about 1000-fold more resistant to inhibition by the modulator protein (inhibitor-2). In contrast with the free catalytic subunit, the reconstituted enzyme co-sedimented with glycogen, and it was able to activate purified liver glycogen synthase b. Also, the synthase phosphatase activity was synergistically increased by a cytosolic phosphatase and inhibited by physiological concentrations of phosphorylase alpha and of Ca2+. PMID- 1898725 TI - Determination of the kinetic mechanism of arginine-specific ADP ribosyltransferases using a high performance liquid chromatographic assay. AB - A high performance liquid chromatographic method has been developed for the assay of arginine-specific ADP-ribosyl transferases. The assay utilizes L-arginine methyl ester (LAME) as the acceptor substrate. ADP-ribosylated-LAME is separated from the reaction mixture using a C-8 reversed-phase column. Before injection, the assay mixture is derivatized with an orthophthaldialdehyde/2-mercaptoethanol reagent. Fluorescence detection of the orthophthaldialdehyde-derivatized product provides excellent sensitivity and a limit of detection of less than 100 fmol. The kinetic mechanism of two arginine-specific ADP-ribosyltransferases, cholera toxin A subunit and an endogenous transferase from rabbit skeletal muscle, were both determined to be random sequential. The kinetic studies utilized 3 aminobenzamide and NG-monomethylarginine as competitive inhibitors for NAD and LAME, respectively. Cholera toxin was reported to have Km values of 5.6 and 39 mM for NAD and LAME, respectively. Km values of 0.56 and 1.2 mM were determined for NAD and LAME, respectively, using the transferase from rabbit skeletal muscle. PMID- 1898726 TI - Structural role of serine 127 in the NADH-binding site of human NADH-cytochrome b5 reductase. AB - Serine 127 of human NADH-cytochrome b5 reductase was replaced by proline and alanine by site-directed mutagenesis. The former mutation has been found in the genes of patients with hereditary deficiency of the enzyme. Both the mutant enzymes (Ser-127----Pro mutant and Ser-127----Ala mutant) were overproduced in Escherichia coli and purified to homogeneity. The two purified mutant enzymes showed indistinguishable spectral properties which differed from those of the wild-type enzyme. The mutant enzymes showed higher molecular extinction coefficients at 462 nm than that of the wild-type enzyme. Quenching of FAD fluorescence in these mutant enzymes was significantly less than that in the wild type enzyme. Furthermore, circular dichroism spectra of the mutant enzymes were different, in both the visible and ultraviolet regions, from that of the wild type enzyme. The spectra of the mutant enzymes in the visible region were restored to almost the same spectrum as the wild type upon reduction with NADH. Ser-127----Pro mutant and Ser-127----Ala mutant showed very low Kcat/Km (NADH) values (5 x 10(7) and 3.5 x 10(7) s-1 M-1, respectively) with cytochrome b5 as an electron acceptor, than that of the wild-type enzyme (Kcat/Km (NADH) = 179 x 10(7) s-1 M-1), while the Kcat/Km (cytochrome b5) value for each enzyme was similar. The mutant enzymes were less thermostable than the wild-type enzyme. These results indicate that serine 127 plays an important role to maintain the structure of the NADH-binding site in the enzyme. PMID- 1898727 TI - Newly made phosphatidylserine and phosphatidylethanolamine are preferentially translocated between rat liver mitochondria and endoplasmic reticulum. AB - The translocation of: (i) phosphatidylserine (PtdSer) from its site of synthesis on microsomal membranes to its site decarboxylation in mitochondrial membranes and (ii) phosphatidylethanolamine (PtdEtn) from the mitochondria to its site of methylation to phosphatidylcholine on microsomal membranes has been reconstituted in cell-free systems consisting of rat liver mitochondria and microsomes. Two types of systems have been reconstituted. In one, the translocation of newly made PtdSer or PtdEtn was examined by incubation of microsomes and mitochondria with [3-3H]serine. In the other, membranes were prelabeled with radioactive PtdSer or PtdEtn, and the transfer of these two lipids between mitochondria and microsomes was monitored. For the transfer of both PtdSer from microsomes to mitochondria and PtdEtn from mitochondria to microsomes, newly made phospholipids were translocated much more readily than pre-existing phospholipids. The data suggest that with respect to their translocation between these two organelles, the pools of newly synthesized PtdSer and PtdEtn were distinct from the pools of "older" phospholipids pre-existing in the membranes. Transfer of neither phospholipid in vitro depended on the presence of cytosolic proteins (i.e. soluble phospholipid transfer proteins) or on the hydrolysis of ATP, although there was some stimulation of PtdSer transfer by ATP and several other nucleoside mono-, di-, and triphosphates. The data are consistent with a collision-based mechanism in which the endoplasmic reticulum and mitochondria come into contact with one another, thereby effecting the transfer of phospholipids. The proposal that there is contact between the endoplasmic reticulum and mitochondria is supported by the recent isolation of a membrane fraction having many, but not all, of the properties of the endoplasmic reticulum, but which was isolated in association with mitochondria (Vance, J. E. (1990) J. Biol. Chem. 265, 7248-7256). PMID- 1898728 TI - Cloning of two human liver bilirubin UDP-glucuronosyltransferase cDNAs with expression in COS-1 cells. AB - We report the isolation and characterization of two human liver cDNA clones, HUG Br1 and HUG-Br2; each encodes a UDP-glucuronosyltransferase enzyme which glucuronidates bilirubin IX alpha to form both the IX alpha C8 and IX alpha C12 monoconjugates and a diconjugate. HUG-Br1 cDNA (2351 base pairs) and HUG-Br2 cDNA (2368 base pairs) encode proteins with 533 and 534 amino acid residues, respectively, with a typical membrane-insertion signal peptide, membrane-spanning domain, and 3 or 5 potential asparagine-linked glycosylation sites. At the nucleic acid and deduced amino acid sequence levels the two clones are 82% similar overall, 66% similar in the amino termini, and identical after codon 287, thus encoding proteins with the same carboxyl terminus. The mRNA encoding HUG-Br1 is of high abundance, and the one encoding HUG-Br2 is of low abundance; both are 2.6 kilobases in length. Both messages (2.6 kilobases) were present in the explanted liver of a Type I Crigler-Najjar patient, although the level for that of HUG-Br1 was reduced 4.5-fold. Northern blot analysis of poly(A)+ RNA isolated from the liver of an untreated and a phenobarbital-treated Erythrocebus patas monkey with 5'-specific probes for each clone indicated that the HUG-Br2-encoded message is induced two fold, but that for HUG-Br1 is not. These data indicate that bilirubin is glucuronidated by at least two different proteins, most likely present in very different amounts. These cDNAs which encode functional bilirubin UDP-glucuronosyltransferases will allow the isolation of an appropriate gene to develop a gene therapy model for patients which have the totally deficient trait. PMID- 1898729 TI - Bacillus subtilis alkaline phosphatases III and IV. Cloning, sequencing, and comparisons of deduced amino acid sequence with Escherichia coli alkaline phosphatase three-dimensional structure. AB - Bacillus subtilis has an alkaline phosphatase multigene family. Two members of this gene family, phoAIII and phoAIV, were cloned, taking advantage of in vitro constructed strains containing a plasmid insertion within one or the other of the structural genes. The DNA sequences of the two genes showed approximately 64% identity at the DNA level and 63% identity in the deduced primary amino acid sequences. The phoAIII and phoAIV genes code for predicted proteins of 47,149 and 45,935 Da, respectively. Comparison of the deduced primary amino acid sequence of the mature proteins with other sequenced alkaline phosphatases from Escherichia coli, yeast, and humans shows 25-30% identity. Based on the refined crystal structure of E. coli alkaline phosphatase, it appears that the active site and the core of the structure are retained in both Bacillus alkaline phosphatases. However, both proteins are truncated at the amino terminus compared with other mature alkaline phosphatases, three sizable surface loops of E. coli are deleted, and a minidomain is replaced with a larger domain in the model. Neither Bacillus alkaline phosphatase sequenced contains any cysteine residues, an amino acid implicated in intrachain disulfide bond formation in other alkaline phosphatases. PMID- 1898730 TI - Tyrosinases from two different loci are expressed by normal and by transformed melanocytes. AB - Two pigmentation related genes have recently been cloned which map to the brown (b) and albino (c) loci of mice; these loci influence the quality and quantity, respectively, of melanin produced by melanocytes. Both these gene products are biochemically similar and have extensive amino acid sequence similarity to each other and to lower forms of tyrosinase (EC 1.14.18.1), a copper binding enzyme responsible for melanin production. In order to characterize the catalytic activities of these molecules, we have synthesized peptides and prepared antibodies to them which specifically recognize the gene products in question. By use of immune affinity purification protocols, we have isolated the proteins encoded by the brown and albino loci and have determined that both have the catalytic functions ascribed to tyrosinase, i.e. hydroxylation of tyrosine to 3,4 dihydroxyphenylalanine (DOPA) and the oxidation of DOPA to DOPAquinone. These are the critical reactions to melanogenesis since melanin pigment can be spontaneously produced from those products. The specific activity of the albino locus encoded product is considerably higher than that of the protein encoded by the brown locus, although the latter protein is present in higher quantity in melanocytes than is the protein encoded by the albino locus. These results are surprising since it was anticipated that tyrosinase was the product of single gene locus, and suggest that regulation of melanogenesis in mammals is controlled at the enzymatic level by several different gene products. PMID- 1898731 TI - Constitutive phosphorylation of the epidermal growth factor receptor blocks mitogenic signal transduction. AB - The epidermal growth factor (EGF) receptor is phosphorylated by protein kinase C at Thr654. It has been proposed that the phosphorylation of this site is an important regulatory mechanism for the control of EGF receptor function. However, the physiological significance of the phosphorylation of EGF receptor Thr654 in intact cells is not understood. To address this question, the design of an experimental strategy is required that can be used to distinguish between the pleiotropic effects of kinase C activation and the specific effects of kinase C that are mediated by the phosphorylation of the EGF receptor at Thr654. The approach that we used was to examine the function of EGF receptors that are constitutively phosphorylated at residue 654. It was observed that the constitutive phosphorylation of the EGF receptor blocked mitogenic signal transduction by the receptor. These data are consistent with the hypothesis that the phosphorylation of the EGF receptor at residue 654 in intact cells inhibits EGF-stimulated cellular proliferation. PMID- 1898732 TI - Low molecular weight GTP-binding proteins in human neutrophil granule membranes. AB - Degranulation of neutrophils involves the differential regulation of the exocytosis of at least two populations of granules. Low molecular weight GTP binding proteins (LMW-GBPs) have been implicated in the regulation of vesicular traffic in the secretory pathways of several types of cells. In the present study we identify distinct subsets of LMW-GBPs associated with the membranes of neutrophil-specific and azurophilic granules. Ninety-four percent of total [35S]guanosine 5'-(3-O-thio)triphosphate (GTP gamma S) binding activity was equally distributed between the plasma membrane and cytosol with the remaining 6% localized in the granules. In contrast, the cytosol contained only 10% of the total GTPase activity while the specific granules accounted for 13%. [alpha 32P]GTP binding to proteins transferred to nitrocellulose revealed LMW-GBPs in all fractions except the azurophilic granules. The specific granules contained three out of four bands which were found in the plasma membrane; these ranged from 20 to 23 kDa and all were resistant to alkaline extraction. Photoaffinity labeling with [alpha-32P]8-azido-GTP in the presence of micromolar Al3+ identified proteins of 25 and 26 kDa unique to azurophilic granules; these could not be labeled with [alpha-32P]8-azido-ATP and could be extracted by acidic but not alkaline pH. Botulinum C3-mediated [32P]ADP-ribosylation identified proteins of 16, 20, and 24 kDa both in plasma membranes and those of specific granules. An anti-ras monoclonal antibody, 142-24E5, recognized a 20-kDa protein localized to the plasma and specific granule membranes which could not be extracted by alkaline pH, was not a substrate for botulinum C3 ADP-ribosyltransferase, and was translocated from specific granules to plasma membrane after exposure of neutrophils to phorbol myristate acetate. We conclude that neutrophil-specific and azurophilic granules contain distinct subsets of LMW-GBPs which are uniquely situated to regulate the differential exocytosis of these two compartments. PMID- 1898733 TI - Functional limits of conformation, hydrophobicity, and steric constraints in prokaryotic signal peptide cleavage regions. Wild type transport by a simple polymeric signal sequence. AB - These experiments examine the role of conformation, hydrophobicity, and steric constraints in the function of the prokaryotic signal peptide cleavage region. The experimental strategy involves replacement of the wild type Escherichia coli alkaline phosphatase signal peptide cleavage region with a series of idealized model sequences designed to epitomize the particular structural and physical variables under study. By analyzing model sequences whose conformations have been determined by physical studies, we have demonstrated that efficient transport does not depend on the structural preference of the cleavage region. Although previous studies based on Chou-Fasman analysis have suggested that the cleavage region forms a beta-turn which is required for transport, our results demonstrate that either a beta-turn- or alpha-helix-fostering sequence in the cleavage region functions indistinguishably from wild type. Furthermore, the presence of a proline residue between the core and cleavage region, although common in natural sequences, is not essential for export. Cleavage regions of varying hydrophobicities can support translocation across the inner membrane, but the placement of bulky residues at positions -1 and -3 upstream of the cleavage site abolishes processing and transport to the periplasm. By reducing the signal peptide to simplified, idealized segments, this study has identified a largely polymeric sequence, MKQST(L10)-(A6), that functions equivalently to the wild type alkaline phosphatase signal peptide. This work starts to provide a basis for the design of a universal prokaryotic signal peptide that incorporates all the critical physical and structural characteristics required for transport function. PMID- 1898734 TI - Structure and function in galactosyltransferase. Sequence locations of alpha lactalbumin binding site, thiol groups, and disulfide bond. AB - The region(s) of bovine galactosyltransferase that interacts with the lactose synthase regulatory protein alpha-lactalbumin was investigated using trace 3H acetylation to probe the effects of alpha-lactalbumin on the reactivities of the individual amino groups of galactosyltransferase. In the presence of Mn2+, alpha lactalbumin was found to reduce the reactivities of lysines 93 and 181 and to increase the reactivities of one or more of lysines 230, 237, and 241. The addition of N-acetylglucosamine (20 mM), which enhances complex formation between the two proteins, did not significantly alter the pattern of perturbation. These results indicate that the NH2-terminal region of the catalytic domain of galactosyltransferase, and possibly part of the proline-rich "stem" region, is affected by the association with alpha-lactalbumin and is therefore implicated in the binding of acceptor substrates. In a separate study only cysteines 176, 266, and 342 of galactosyltransferase were found to react with [3H]iodoacetic acid under denaturing conditions. From their lack of reactivity it is deduced that the remaining two cysteines, residues 134 and 247, are joined in a disulfide linkage. From these results and those of a previous study of UDP-galactose binding (Yadav, S., and Brew, K. (1990) J. Biol. Chem. 265, 14163-14169) it appears that the soluble form of galactosyltransferase is composed of two domains, the NH2 terminal 150 residues containing the Cys134-Cys247 disulfide bond, which functions in alpha-lactalbumin and acceptor binding, and the COOH-terminal region, which is involved in UDP-galactose binding. PMID- 1898735 TI - Sulfation of Tyr1680 of human blood coagulation factor VIII is essential for the interaction of factor VIII with von Willebrand factor. AB - The acidic region of the Factor VIII light chain was studied with regard to structural requirements for the formation of a functional von Willebrand factor (vWF)-binding site. Factor VIII mutants lacking the B domain, with additional deletions and an amino acid replacement within the sequence 1649-1689 were constructed using site-directed mutagenesis and expressed in Cos-1 cells. These mutants, which were recovered as single-chain molecules with similar specific activities, were compared in their binding to immobilized vWF. Deletion of amino acids 741-1648 or 741-1668 did not affect the binding of Factor VIII to vWF. However, a mutant with a deletion of residues 741-1689 was no longer capable of interacting with vWF. This indicates a role for residues within the sequence 1669 1689 in the formation of a vWF-binding site. When recombinant Factor VIII was expressed in the presence of chlorate, an inhibitor of protein sulfation, the resulting Factor VIII displayed strongly reduced binding to vWF. vWF binding was completely abolished when within the sequence 1669-1689 the tyrosine residue Tyr1680, which is part of a consensus tyrosine sulfation sequence, was replaced by phenylalanine. The Factor VIII sequence 1673-1689 was identified as a high affinity substrate for tyrosylprotein sulfotransferase (Km = 57 microM) in cell free sulfation studies. It is concluded that sulfation of Tyr1680 is required for the interaction of Factor VIII with vWF. Two synthetic peptides that represent the sequence 1673-1689, but differ with respect to sulfation of Tyr1680 are shown to have vWF binding affinity that is considerably lower than the Factor VIII protein. Several models to accommodate our findings are discussed. PMID- 1898736 TI - Chondroitin 4-sulfate covalently cross-links the chains of the human blood protein pre-alpha-inhibitor. AB - The human blood protein pre-alpha-inhibitor is composed of one heavy and one light protein chain. The chains are covalently linked to each other by a structure that has not previously been described, which we designate a protein glycosaminoglycan-protein (PGP) cross-link. A combination of protein and carbohydrate analytical techniques indicates that the interchain linkage is mediated by a chondroitin 4-sulfate glycosaminoglycan that originates from a typical O-glycosidic link to Ser-10 of the light chain. The heavy chain is esterified, via the alpha-carbon of its C-terminal Asp, to C-6 of an internal N acetylgalactosamine of the glycosaminoglycan chain. This PGP cross-link may be present in other proteins, but could have been overlooked due to the heterogeneous behavior of proteins containing glycosaminoglycan. PMID- 1898737 TI - Synthesis and secretion of plasminogen activator inhibitor 1 by human endothelial cells in vitro. Effect of active site mutagenized tissue-type plasminogen activator. AB - The effects of recombinant tissue-type plasminogen activator (rt-PA) and of an inactive mutant of rt-PA, obtained by mutagenesis of the active site Ser478 to Ala (rt-PA-Ala478), on the synthesis and secretion of plasminogen activator inhibitor-1 (PAI-1) by human umbilical vein endothelial cells (HUVEC) in culture were studied. Under base-line conditions, PAI-1 antigen secretion was 4.3 +/- 1.0 micrograms (mean +/- S.D., n = 8) per 10(6) cells in 24 h. This PAI-1 had a low specific activity (6,000 +/- 1,600 units/mg) and Mr of 50,000, which was not altered by addition of rt-PA. In HUVEC cultured with 2 micrograms/ml rt-PA Ala478, PAI-1 antigen secretion was 2.1 +/- 0.8 micrograms (n = 5) per 10(6) cells in 24 h with a specific activity of 120,000 +/- 42,000 units/mg and Mr of 50,000. Addition of rt-PA to this conditioned medium resulted in generation of three main components: 16% migrated as an Mr 106,000 rt-PA.PAI-1 complex, 16% as an Mr 81,000 degraded rt-PA.PAI-1 complex and the remainder as an Mr 45,000 degradation product of PAI-1. HUVEC cultured with 2 micrograms/ml rt-PA secreted 3.9 +/- 0.6 micrograms (n = 8) PAI-1 antigen per 10(6) cells within 24 h, of which 20-50% occurred as intact or degraded complexes with t-PA (Mr 106,000 and 81,000) and the rest as an inactive Mr 45,000 degradation product of PAI-1. PAI-1 mRNA levels, determined by Northern blot analysis and expressed relative to beta actin mRNA levels, were very similar for HUVEC cultured in the absence or the presence of rt-PA or rt-PA-Ala478. It is concluded that PAI-1 is secreted by HUVEC in culture in fully active form which spontaneously inactivates. PAI-1 can be stabilized by addition of rt-PA-Ala478 to the culture medium, resulting in a 20-fold increase in specific activity. Interaction of rt-PA with active PAI-1 produces both t-PA.PAI-1 complex and an inactive degradation product of PAI-1. PMID- 1898738 TI - Magnesium transport in Salmonella typhimurium. Regulation of mgtA and mgtB expression. AB - Salmonella typhimurium contains three distinct transport systems (CorA, MgtA, and MgtB) that move Mg2+ across the cytoplasmic membrane. Mutant strains containing only one of these three systems have been constructed and used to study each system in isolation. Characterization of these systems has been hampered, however, by the need to use 28Mg2+, a relatively unavailable, extremely expensive, and short lived radioisotope. This paper reports that 63Ni2+ is transported into the cell by all three of the S typhimurium Mg2+ transport systems. In a strain deficient in all three systems, uptake of 63Ni2+ was undetectable under the conditions used. Comparison of 63Ni2+ uptake kinetics and inhibition of 63Ni2+ transport by other divalent cations suggest that Ni2+ can be used as an analog of Mg2+ in the study of these three transport systems. Using 63Ni2+ to measure uptake, the effect of Mg2+ levels in the growth medium on transport by each system was tested. Transport by the CorA system was unaffected by changes in the amount of Mg2+ in the growth medium. In contrast, uptake via MgtA and MgtB was significantly increased in cells grown in 10 microM extracellular Mg2+ compared to cells grown in 10 mM Mg2+. The increases in uptake were the result of increases in Vmax without change in Km. This result suggests that, in low Mg2+ medium, cells contained higher levels of the transporters. Production of beta-galactosidase from mgtA::lacZ and mgtB::lacZ but not corA::lacZ fusions was also increased when cells were grown in low extracellular concentrations of Mg2+ indicating that the regulation occurs at the level of transcription. Expression of beta-galactosidase was also inhibited by the addition of other divalent cations including Ca2+ and Mn2+. Regulation of transcription from the mgtA and mgtB promoters was similar over the range of extracellular Mg2+ concentrations from 10 microM to 10 mM. At 1 microM, however, transcription from the mgtB promoter, as measured by beta-galactosidase levels in a mgtB::lacZ transcriptional fusion strain, was increased over 800-fold, and Ca2+ could no longer inhibit transcription effectively. In contrast, growth at 1 microM extracellular Mg2+ increased transcription from the mgtA promoter only about 30-fold and Ca2+ could still inhibit this increase. These results suggest that at least two distinct mechanisms are responsible for regulation of the mgtA and mgtB transcription in response to extracellular cation concentration. PMID- 1898739 TI - Activation and inhibition of bovine carbonic anhydrase III by dianions. AB - We have found that many dianionic species, at millimolar concentrations, significantly activate or inhibit the bovine carbonic anhydrase III-catalyzed hydration of CO2. Dianionic species such as HPO2-4 and SO2-3, with pKb values near 7, are activators, whereas weakly basis species such as SO2-4 act as inhibitors. Both activation and inhibition are partial hyperbolic in nature and do not appear to compete with monoanionic linear inhibitors like N-3. Our kinetic data are consistent with a formal mechanism of action for carbonic anhydrase III that is directly analogous to that of carbonic anhydrase II, in which Lys-64 of carbonic anhydrase III can act as an intramolecular H+ transfer group during CO2 hydration. Our data suggest that dianionic inhibitors depress the rate of H+ transfer during turnover by stabilizing the protonated form of Lys-64. We postulate that dianionic activators enhance the rate of a rate-limiting H+ transfer step in the mechanism, probably by acting directly as H+ acceptors. PMID- 1898740 TI - In vitro assembly of the functional porin trimer from dissociated monomers in Pseudomonas aeruginosa. AB - The molecular weights of monomeric and oligomeric forms of the newly identified porins, protein D2, of the outer membrane of Pseudomonas aeruginosa appeared to be 47,000 and 137,000, respectively, as determined by the light scattering technique. Presence of the trimeric aggregates of the homologous subunits in the intact outer membrane, the liposome membrane, and the non-ionic surfactant were confirmed through cross-linking experiments and immunoblotting techniques. The protein D2 monomers prepared in 0.1% of sodium dodecyl sulfate at 23 degrees C spontaneously reassembled into the trimeric aggregate when the surfactant dropped below critical concentration. The diffusion rates of saccharides and beta-lactam antibiotics through the liposome membranes reconstituted from the reassembled protein D2 trimers were indistinguishable from those of the native protein D2. This study shed some light on the porin trimer assembly as well as on the mechanism of carbapenem diffusion through the protein D2 pores. PMID- 1898741 TI - Expression of rat jejunal cystine carrier in Xenopus oocytes. AB - Functional interactive cystine-lysine carriers have been expressed in Xenopus oocytes following the injection of RNA extracted from rat intestinal mucosa. Lysine-inhibitable cystine uptake was able to be measured 16 h after oocyte injection with RNA. The longer the oocytes were maintained after injection, the more cystine transport capability was induced. Uninjected or water-injected oocytes showed virtually no lysine-inhibitable cystine uptake, and no system developed after the oocytes had been isolated and maintained in vitro. The cystine uptake expressed after RNA injection was selectively inhibited by dibasic amino acids and phenylalanine but not by other amino acids or alpha-methyl-D glucoside. Expression of the interactive cystine-lysine system was induced only by RNA isolated from intestinal tissue and not by RNA from rat liver. The Km for cystine uptake in RNA-injected oocytes was 0.01 mM and appears identical to the single system found in the RNA source tissue. PMID- 1898742 TI - Sequence of the clathrin heavy chain from Saccharomyces cerevisiae and requirement of the COOH terminus for clathrin function. AB - The sequence of the clathrin heavy chain gene, CHC1, from Saccharomyces cerevisiae is reported. The gene encodes a protein of 1,653 amino acids that is 50% identical to the rat clathrin heavy chain (HC) (Kirchhausen, T., S. C. Harrison, E. P. Chow, R. J. Mattaliano, R. L. Ramachandran, J. Smart, and J. Brosius. 1987. Proc. Natl. Acad. Sci. USA. 84:8805-8809). The alignment extends over the complete length of the two proteins, except for a COOH-terminal extension of the rat HC and a few small gaps, primarily in the globular terminal domain. The yeast HC has four prolines in the region of the rat polypeptide that was proposed to form the binding site for clathrin light chains via an alpha helical coiled-coil interaction. The yeast protein also lacks the COOH-terminal Pro-Gly rich segment present in the last 45 residues of the rat HC, which were proposed to be involved in the noncovalent association of HCs to form trimers at the triskelion vertex. To examine the importance of the COOH terminus of the HC for clathrin function, a HC containing a COOH-terminal deletion of 57 amino acids (HC delta 57) was expressed in clathrin-deficient yeast (chc1-delta). HC delta 57 rescued some of the phenotypes (slow growth at 30 degrees, genetic instability, and defects in mating and sporulation) associated with the chc1-delta mutation to normal or near normal. Also, truncated HCs were assembled into triskelions. However, cells with HC delta 57 were temperature sensitive for growth and still displayed a major defect in processing of the mating pheromone alpha-factor. Fewer coated vesicles could be isolated from cells with HC delta 57 than cells with the wild-type HC. This suggests that the COOH-terminal region is not required for formation of trimers, but it may be important for normal clathrin coated vesicle structure and function. PMID- 1898743 TI - Effect of deslorelin dose in the treatment of central precocious puberty. AB - Central precocious puberty is effectively treated with long-acting LHRH analogs (LHRHas). Although at least six LHRHas have now been used in children, there have been no studies to determine the least effective dose of any of these analogs. We sought to determine the effect of decreasing an efficacious dose of deslorelin (D Trp6-Pro9-NEt-LHRH) on basal and LHRH-stimulated gonadotropins, estradiol levels, and the rates of linear growth and skeletal maturation in subjects with central precocious puberty. Twenty-nine children with central precocious puberty were enrolled in a double blinded study. All subjects were treated for the initial 3 months with deslorelin at a dose (4 micrograms/kg.day, sc) known to suppress gonadotropins, linear growth velocity, and the rate of skeletal maturation. After 3 months, the subjects were randomly assigned to receive one of three daily sc doses of deslorelin: 4 micrograms/kg (n = 9), 2 micrograms/kg (n = 11), or 1 micrograms/kg (n = 9). They were treated at this dose in double blinded fashion for 15 months, after which time they resumed therapy at a dose of 4 micrograms/kg.day for an additional year. The children in the three groups did not differ in terms of chronological age, bone age, pretreatment growth rate, or Tanner stage at the onset of therapy. Similarly, there were no differences in the clinical and hormonal responses to the first 3 months of LHRHa therapy (4 micrograms/kg.day). During the 15-month period at the three different doses, the three dose groups could not be distinguished from each other in terms of pubertal stage, linear growth velocity, rate of skeletal maturation, sex steroid levels, mean LH or FSH levels, or peak FSH response to LHRH stimulation or to a dose of deslorelin. In contrast, the peak LH response to LHRH stimulation was highest in children treated with the lowest dose (1 micrograms/kg.day; P less than 0.025, by multiple analysis of variance). In addition, the peak LH response to a dose of deslorelin (the LHRHa test) was higher in children treated with 1 micrograms/kg.day than in those treated with 4 micrograms/kg.day (P less than 0.04). In summary, the LHRHa test is a sensitive means for detecting activation of the hypothalamic-pituitary-gonadal axis, and deslorelin at a dose of 1 micrograms/kg.day results in less gonadotropin suppression than a dose of 4 micrograms/kg.day.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1898744 TI - A direct effect of hyperinsulinemia on serum sex hormone-binding globulin levels in obese women with the polycystic ovary syndrome. AB - To determine whether hyperinsulinemia can directly reduce serum sex hormone binding globulin (SHBG) levels in obese women with the polycystic ovary syndrome, six obese women with this disorder were studied. Before study, ovarian steroid production was suppressed in each woman by the administration of 7.5 mg of a long acting GnRH agonist, leuprolide depot, im, on days -56, -28, and 0. This resulted in substantial reductions in serum concentrations of testosterone (from 1.72 +/- 0.29 nmol/L on day -56 to 0.32 +/- 0.09 nmol/L on day 0), non-SHBG-bound testosterone (from 104 +/- 16 pmol/L on day -56 to 19 +/- 5 pmol/L on day 0), androstenedione (from 7.25 +/- 1.65 nmol/L on day -56 to 2.78 +/- 0.94 nmol/L on day 0), estrone (from 371 +/- 71 pmol/L on day -56 to 156 +/- 29 pmol/L on day 0), estradiol (from 235 +/- 26 pmol/L on day -56 to 90 +/- 24 pmol/L on day 0), and progesterone (from 0.28 +/- 0.12 nmol/L on day -56 to 0.08 +/- 0.02 nmol/L on day 0). Serum SHBG levels, however, did not change (18.8 +/- 2.8 nmol/L on day 56 vs. 17.8 +/- 2.6 nmol/L on day 0). While continuing leuprolide treatment, the women were administered oral diazoxide (300 mg/day) for 10 days to suppress serum insulin levels. Diazoxide treatment resulted in suppressed insulin release during a 100-g oral glucose tolerance test (insulin area under the curve, 262 +/- 55 nmol/min.L on day 0 vs. 102 +/- 33 nmol/min.L on day 10; P less than 0.05) and deterioration of glucose tolerance. Serum testosterone, androstenedione, estrone, estradiol, and progesterone levels did not change during combined diazoxide and leuprolide treatment. In contrast, serum SHBG levels rose by 32% from 17.8 +/- 2.6 nmol/L on day 0 to 23.5 +/- 2.0 nmol/L on day 10 (P less than 0.003). Due primarily to the rise in serum SHBG levels, serum non-SHBG-bound testosterone levels fell by 43% from 19 +/- 5 pmol/L on day 0 to 11 +/- 4 pmol/L on day 10 (P = 0.05). These observations suggest that hyperinsulinemia directly reduces serum SHBG levels in obese women with the polycystic ovary syndrome independently of any effect on serum sex steroids. PMID- 1898745 TI - Caloric restriction affects liver microsomal monooxygenases differentially in aging male rats. AB - Caloric restriction (CR) extends life span and retards the onset of physiological changes and pathologies associated with aging, but the underlying mechanisms remain unresolved. This study demonstrates that CR postpones the documented age related declines in and/or enhances the activity and microsomal concentration of several liver monooxygenases in male rats, i.e., NADPH cytochrome P-450 reductase, total cytochromes P-450. However, the relative concentration of cytochrome P-450b+C did not exhibit statistically significant changes, whereas another isozyme, the male specific P-450h, declined significantly in both ad libitum-fed and CR rats as a function of increasing age. While CR appears to retard age-associated changes in certain liver enzymes, this effect is by no means universal. The hepatic monooxygenases constitute a well-characterized enzyme system in which to examine the perturbation of the aging process by CR. PMID- 1898746 TI - The effect of aging on submaximal exercise performance and recovery. AB - The upward drift of gas exchange variables during 70% maximal exercise and recovery half-times in aged and young subjects of equivalent age-predicted aerobic capacity was measured. In the aged subjects, upward drift of VE, VO2, and HR was reduced compared with the young group. The recovery of VE, VCO2, and VO2 was slowed in the aged. However, at 10 minutes post-exercise, VCO2, VO2, and HR had returned to similar relative values for both groups; in the young subjects VE remained elevated at the end of recovery. The reduced upward drift of gas exchange variables and HR during exercise in aged subjects is consistent with an attenuated response of glycogenolysis and lactate production to adrenergic stimulation and/or to selective loss of type II skeletal muscle fibers. The slowed recovery of VE, VCO2, and VO2 in elderly persons is consistent with age related reduced CO2 chemosensitivity, delaying elimination of the exercise induced CO2 load. PMID- 1898747 TI - The regulation of synaptogenesis during normal development and following activity blockade. AB - The mature neuromuscular junction is characterized by the tight spatial colocalization of synaptic vesicles and acetylcholine receptor (AChR) clusters. Although a large body of work exists on the interactions between motoneurons and myotubes leading to synaptogenesis in tissue culture, how the neuromuscular junction acquires its highly specialized structure in vivo is not well understood, particularly during the earliest period of synaptogenesis. In this study, the development of the neuromuscular synapse in chick hindlimb muscles was examined and quantified by simultaneously labeling the pre- and postsynaptic elements from the time the main nerve trunks leave the lumbosacral plexus region to enter the developing limb (St 24) through the end of the motoneuron cell death period (St 36). Based on these results, synaptogenesis can be divided into several distinct stages that are intimately connected to the innervation sequence described in a previous paper (Dahm and Landmesser, 1988). Briefly, as large nerve trunks approach the developing muscles and the first AChR clusters are induced to form on nearby myotubes, none of these initial receptor clusters are in direct contact with a nerve profile. The first appearance of nerve-contacted clusters (synapses) is coincident with the growth of large, unbranched nerve trunks into the muscles. The next step is initiated by the formation of small nerve side branches that grow out from the larger intramuscular nerve trunks to bring most axons and myotubes into contact for the first time. As side branches form, synapses appear around them, and non-nerve-contacted receptor clusters disappear from around the main intramuscular nerve trunks. The next step in synaptogenesis is the restriction of synaptic vesicle antigen to sites of synaptic contact. These early stages of synaptogenesis are also characterized by the growth of the presynaptic terminal to match the length of the postsynaptic receptor cluster. This study showed that AChR cluster formation during early in vivo neuromuscular development does not require close anatomical nerve contact, but that the presence of the nerves is necessary for AChR clusters to form. This suggests that the nerves normally induce AChR clustering via the release of a diffusible substance, a suggestion substantiated by the observation that AChR clusters do not form on aneural myotubes in vivo. In order to assess the role of synapse formation in the regulation of motoneuron number, synaptogenesis was quantitatively examined after chronic neuromuscular blockade, which prevents motoneuron cell death.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1898748 TI - Calculations of "predicted" serum sodium concentration in diabetic ketoacidosis. PMID- 1898749 TI - Strategies for diagnosis and treatment of children at risk for occult bacteremia: clinical effectiveness and cost-effectiveness. AB - Decision analysis was used to evaluate the probable health benefits, complications, and costs of six management strategies for febrile children at risk for occult bacteremia. The strategy that combined blood culture with empiric oral antibiotic treatment for all patients was predicted to prevent the highest number of major infections and to have the lowest cost per major infection prevented. The strategy that combined a leukocyte count and blood culture for all patients, followed by empiric antibiotic treatment for those with leukocyte count greater than or equal to 10,000/mm3, had almost equal cost and clinical effectiveness and avoided many antibiotic complications. Culture of blood specimens from all patients and no empiric treatment constituted the third most clinically effective intervention but was the least cost-effective in this model. Giving a 2-day oral course of amoxicillin without testing had the lowest average cost per febrile patient but was the least clinically effective intervention. However, the low degree of effectiveness of empiric treatment alone was based on the assumption that oral amoxicillin therapy was only 20% effective in preventing major infections after bacteremia. At higher estimates of effectiveness, treatment alone became a more viable strategy. We conclude that approaches which combine blood culture with empiric antibiotic treatment are the most clinically effective and the most cost-effective strategies for children at risk for occult bacteremia. PMID- 1898751 TI - Total parenteral nutrition in the newborn infant: energy substrates and respiratory gas exchange. AB - The hypothesis that a high-fat parenteral regimen was beneficial for respiratory gas exchanges, in comparison with a high-glucose regimen, was tested in a paired crossover design. Ten parenterally fed newborn infants with no respiratory problems received two 5-day isoenergetic and isonitrogenous regimens that differed in their nonprotein source of energy; the level of fat intake (low fat (LF) 1 gm.kg-1.day-1; high fat (HF) 3 gm.kg-1.day-1) varied inversely with that of glucose. Continuous transcutaneous PO2 (tcPO2) and PCO2 (tcPCO2), respiratory gas exchange (indirect calorimetry), and plasma arachidonate metabolites were measured at the end of each regimen. Oxygen consumption and resting energy expenditure were not affected by modification of the source of energy. However, carbon dioxide production (VCO2) was higher during LF than during HF (6.9 +/- 0.2 vs 6.2 +/- 0.1 ml.kg-1.min-1; p less than 0.01), as was the respiratory quotient (1.08 +/- 0.02 vs 0.96 +/- 0.02; p less than 0.001). Despite the differences in VCO2, the tcPCO2 was not affected, suggesting adequate pulmonary compensation during LF, as documented by the higher minute ventilation (160 +/- 7 vs 142 +/- 5 ml.kg-1.min-1; p less than 0.01). The lower tcPO2 during the HF regimen (73.8 +/- 2.8 vs 68.8 +/- 2.6 mm Hg; p less than 0.015) indicated a disturbance at the alveolocapillary level induced by the lipid emulsion. No differences were found in circulating levels of prostaglandins and thromboxanes. The substitution of glucose for lipid did not modify fat storage (2.1 +/- 0.3 vs 2.1 +/- 0.3 gm.kg 1.day-1). We conclude that the supposed beneficial effect of a fat emulsion on respiratory gas exchange is questionable. PMID- 1898750 TI - Role of Chlamydia pneumoniae in acute chest syndrome of sickle cell disease. AB - Children with sickle cell disease and acute chest syndrome were investigated for infection with Chlamydia pneumoniae and Mycoplasma pneumoniae. Of 30 patients who had 32 episodes of acute chest syndrome, four (13%) had C. pneumoniae isolated from the nasopharynx; two of these also had serologic evidence of acute infection, and one had positive nasopharyngeal isolates on two subsequent occasions during the course of 1 year with stable, elevated titers of anti-C. pneumoniae IgG, suggesting chronic infection. Two patients with negative cultures had serologic evidence of infection with C. pneumoniae. None of 32 cultures for M. pneumoniae were positive, and although anti-M. pneumoniae IgM developed in two patients, one of these patients had evidence of C. pneumoniae infection (positive culture and seroconversion). We conclude that C. pneumoniae infection is prevalent in our sickle cell population with acute chest syndrome. Until further studies clarify the pathophysiologic significance of C. pneumoniae infection, we believe that early inclusion of erythromycin as antimicrobial therapy for acute chest syndrome seems reasonable. PMID- 1898752 TI - Enhanced immunoglobulin levels correlate with infectious complications after surgery in esophageal cancer. AB - Severe septic complications account for the high mortality of patients with esophageal cancer. We examined the levels of immunoglobulins and complements together with infection-related complications in a large number of patients. Enhancements of IgG, IgA, C3, C4, and CH50 were evident in patients with esophageal cancer and were more predominant compared to findings in cases of gastric cancer. Average levels of IgG and IgA immediately before surgery were significantly higher in esophageal cancer patients with postoperative septic complications than in those without such problems. Preoperative radiation therapy and total parenteral nutrition did not significantly alter the levels of immunoglobulins and complements. It would thus appear that the enhancement of IgG and IgA is associated with the occurrence of infectious complications following surgery for patients with esophageal cancer. PMID- 1898753 TI - Cost-effectiveness of strategies for detecting diabetic retinopathy. AB - A computer model has been developed to determine cost-effectiveness of screening and treatment for diabetic retinopathy from a societal viewpoint. This model was used to evaluate biannual and annual screening programs using ophthalmoscopy, fundus photography with a "nonmydriatic camera," and photography with a "mydriatic camera." Computations were performed for three subpopulations formed by patients with younger onset diabetes (age at diagnosis less than 30 years) of 5 years or more duration, with older onset diabetes (age at diagnosis greater than or equal to 30 years) who are taking insulin, and with older onset diabetes not taking insulin. Population characteristics are from a well-described southern Wisconsin population where data are available, but the computer model may be specialized to other population. Generally costs of screening programs appear to be recovered by avoided costs of blindness in the population subgroups taking insulin; however, the cost of screening programs generally are not recovered by avoiding costs of blindness in the older onset population subgroup not taking insulin. It was estimated that supplying annual examination with mydriatic fundus photography as a screening program to a cohort of 1,000 diabetics from the younger onset population who have been diagnosed at least 5 years and who are currently not receiving care might save 319 sight years over the lifetime of the cohort. This program will save 62 sight years in an older onset cohort who are taking insulin, and 21 sight years in the older onset population not taking insulin (all benefits are presented as present values computed with an annual discount rate of 5%). Other programs achieve slightly lower savings in each subpopulation. PMID- 1898754 TI - Saint Anthony's fire revisited. Vascular problems associated with migraine medication. AB - Ergotamine and related compounds have been used for many years in the management of migraine. This review highlights the potential for toxic effects upon the arterial system which may arise from the use of ergot medications. Data on four female patients aged from 30 to 49 years were collected retrospectively from in patient records and out-patient follow-up between 1978 and 1990. All four patients presented with the symptoms and signs of arterial obstruction and all had been prescribed ergot preparations as treatment and prophylaxis of migraine, for periods ranging from three to 12 years. Two patients had an acute arterial obstruction that resolved completely when the migraine medication was withdrawn. Two had chronic obstructions and radiological and surgical examination gave evidence of arterial stenosis. These two patients were treated with bypass surgery. Review of the literature indicated that other authors had described similar cases but without specifying the methods of data collection. This report supports the findings of others regarding the toxic effects of ergot preparations upon the arterial system, which may take the form of chronic or acute obstruction. General practitioners and physicians should be aware of the possible complications arising from prolonged or excessive use of ergot medications. PMID- 1898755 TI - Tuberculosis in Australia: an unfinished fight. PMID- 1898758 TI - Update: influenza activity--United States, 1990-91. PMID- 1898756 TI - Flinders Island spotted fever: a newly recognised endemic focus of tick typhus in Bass Strait. Part 2. Serological investigations. AB - Twenty-six cases of a spotted-fever-like illness have been identified on Flinders Island, Tasmania, over a 17 year period. These patients and 335 healthy persons from the island were investigated serologically using the Weil-Felix agglutination test (Proteus sp. antigens OX2, OX19, OXK) and rickettsia-specific microimmunofluorescence. The antigens used in these latter tests comprised one member of the typhus group (Rickettsia typhi) and three members of the spotted fever group (Rickettsia rickettsii, Rickettsia australis and Rickettsia conorii). Patients with Flinders Island spotted fever showed a higher prevalence of positive reactions to the Weil-Felix tests (with OX2 and OX19 antigens) and a higher prevalence of positive results to rickettsia-specific serological tests (with the exception of antibodies to Rickettsia typhi) than did healthy persons; OX2 (36% v. less than 1%); OX19 (36% v. less than 1%); Rickettsia rickettsii (42% v. 1%); Rickettsia australis (46% v. 1%); Rickettsia conorii (42% v. 1%); Rickettsia typhi (4% v. 4%). In seven of the 26 patients (27%) seroconversion was demonstrated by means of Weil-Felix tests, confirming recent infection. In six of these patients seroconversion was also demonstrated in rickettsia-specific tests. Although these results support the clinical evidence that the illness on Flinders Island is caused by a rickettsia of the spotted fever group, the aetiological agent remains to be isolated. PMID- 1898757 TI - Mortality attributable to HIV infection/AIDS--United States, 1981-1990. AB - From 1981 through 1990, 100,777 deaths among persons with acquired immunodeficiency syndrome (AIDS) were reported to CDC by local, state, and territorial health departments; almost one third (31,196) of these deaths were reported during 1990. During the 1980s, AIDS emerged as a leading cause of death among young adults in the United States. By 1988, human immunodeficiency virus (HIV) infection/AIDS had become the third leading cause of death among men 25-44 years of age and, by 1989, was estimated to be second, surpassing heart disease, cancer, suicide, and homicide (Figure 1). In 1988, HIV infection/AIDS ranked eighth among causes of death among women 25-44 years of age (Figure 2); in 1991, based on current trends, HIV infection/AIDS is likely to rank among the five leading causes of death in this population (1). PMID- 1898759 TI - Laboratory-acquired meningococcemia--California and Massachusetts. AB - Although Neisseria meningitidis is commonly isolated in clinical laboratories, laboratory-acquired infection is rare (1). This report describes two fatal cases of meningococcal infection in laboratory workers; both of these cases probably were laboratory acquired. PMID- 1898760 TI - Binding of the transcription factor EBP-80 mediates the methylation response of an intracisternal A-particle long terminal repeat promoter. AB - Intracisternal A-particle (IAP) expression in mouse cells has been correlated with hypomethylation of HhaI and HpaII sites in proviral long terminal repeats (LTRs). In a previous study, in vitro methylation of three HhaI sites in the U3 region of the LTR from the cloned genomic IAP element, MIA14, was shown to inhibit promoter activity in vivo. In this study, we found by site-directed mutagenesis that the two more downstream HhaI sites within this LTR were responsible for the methylation effects on promoter activity in vivo; methylation of the other (5') HhaI site, which lies within a putative SP1 binding domain, did not affect promoter activity. Methylation of the HhaI sites also inhibited promoter activity of the LTR in a cell-free transcription system. Exonuclease III footprinting demonstrated methylation-induced changes in protein binding over the region encompassing the downstream HhaI site, designated the Enh2 domain. The protein that interacts specifically with this domain, EBP-80, was characterized in a previous study (M. Falzon and E. L. Kuff, J. Biol. Chem. 264:21915-21922, 1989). We show here that the presence of methylcytosine in the HhaI site within the Enh2 domain inhibited binding of EBP-80 in vitro. The methylated MIA14 LTR construct was much less responsive to added EBP-80 in an in vitro transcription system than was the unmethylated construct. These data suggest that CpG methylation within the Enh2 domain may exert its effect on transcription in vivo by altering the interaction between EBP-80 and its cognate DNA sequence. PMID- 1898761 TI - Overlapping elements in the guanylate-binding protein gene promoter mediate transcriptional induction by alpha and gamma interferons. AB - The gene encoding a 67-kDa cytoplasmic guanylate-binding protein (GBP) is transcriptionally induced in cells exposed to interferon of either type I (alpha interferon [IFN-alpha] or type II (IFN-gamma). The promoter of the GBP gene was cloned and found to contain an IFN-alpha-stimulated response element, which mediated the response of the GBP gene to IFN-alpha. On the basis of transfection experiments with recombinant plasmids, two different elements were delineated. Both were required to obtain the maximal response of the GBP gene to IFN-gamma: the IFN-alpha-stimulated response element and an overlapping element termed the IFN-gamma activation site. Different proteins that act on each element were investigated, and their possible involvement in IFN-gamma-induced transcriptional regulation is discussed. PMID- 1898762 TI - A gene related to the proto-oncogene fps/fes is expressed at diverse times during the life cycle of Drosophila melanogaster. AB - The proto-oncogene fps/fes encodes a distinctive type of protein-tyrosine kinase. We identified a Drosophila gene (dfps85D) whose product resembles the proteins encoded by vertebrate fps/fes and the closely related gene fer. dfps85D is located at chromosomal position 85D10-13 and is unlikely to correspond to any previously defined genetic locus in Drosophila melanogaster. Expression of the gene is entirely zygotic in origin and occurs throughout the life cycle. But hybridization in situ revealed that the pattern of expression is specialized and evolves in a provocative manner. The most notable feature of expression is the diversity of developmental periods, tissues, and cells in which it occurs. In some tissues, expression is transient; in others, it is continuous. Expression occurs in both mitotic and terminally differentiated tissue and, at various times in development, is prominent in imaginal disks, gut, muscle, testes, ovaries, retina, and other neural tissues. It appears that the use of dfps85D is more diversified than that of other Drosophila protein-tyrosine kinases reported to date and contrasts sharply with the restricted expression of fps itself in vertebrates. The detailed description of expression provided here will help guide the search for mutants in dfps85D. PMID- 1898763 TI - Molecular cloning and functional analysis of three subunits of yeast proteasome. AB - The genes encoding three subunits of Saccharomyces cerevisiae proteasome were cloned and sequenced. The deduced amino acid sequences were homologous not only to each other (30 to 40% identity) but also to those of rat and Drosophila proteasomes (25 to 65% identity). However, none of these sequences showed any similarity to any other known sequences, including various proteases, suggesting that these proteasome subunits may constitute a unique gene family. Gene disruption analyses revealed that two of the three subunits (subunits Y7 and Y8) are essential for growth, indicating that the proteasome and its individual subunits play an indispensable role in fundamental biological processes. On the other hand, subunit Y13 is not essential; haploid cells with a disrupted Y13 gene can proliferate, although the doubling time is longer than that of cells with nondisrupted genes. In addition, biochemical analysis revealed that proteasome prepared from the Y13 disrupted cells contains tryptic and chymotryptic activities equivalent to those of nondisrupted cells, indicating that the Y13 subunit is not essential for tryptic or chymotryptic activity. However, the chymotryptic activity of the Y13 disrupted cells is not dependent on sodium dodecyl sulfate (SDS), an activator of proteasome, since nearly full activity was observed in the absence of SDS. Thus, the activity in proteasome of the Y13 disrupted cells might result in unregulated intracellular proteolysis, thus leading to the prolonged cell cycle. These results indicate that cloned proteasome subunits having similar sequences to the yeast Y13 subunit are structural, but not catalytic, components of proteasome. It is also suggested that two subunits (Y7 and Y8) might occupy positions essential to proteasome structure or activity, whereas subunit Y13 is in a nonessential but important position. PMID- 1898765 TI - Dislocation of chromatin elements in prophase induced by diethylstilbestrol: a novel mechanism by which micronuclei can arise. AB - The in vitro micronucleus test with Syrian hamster embryo (SHE) cells assays the induction of micronuclei by chemical agents. Both chromosome fragments and lagging chromosomes can give rise to micronuclei. Nevertheless, only limited information is available on the ultrastructure of micronuclei and the mechanisms of their formation. Diethylstilbestrol (DES), a non-mutagenic carcinogen, as well as its analogue 3.3'-DES induce micronuclei in SHE cells. A comparison of the dose response of DES-induced micronucleus formation with the previously published ones for aneuploidy and transformation shows that all 3 run in parallel. Thus, a functional relationship between these endpoints, in the SHE system, may be implied. The present study is designed to address the formation of micronuclei using supravital UV microscopy, to test for the presence of defined chromosome domains within micronuclei using immunocytochemistry, and to define aspects of their ultrastructure by electron microscopy. Supravital UV microscopy showed that 3.3'-DES induces displacement of chromosomes/chromatids during prophase/anaphase and formation of micronuclei during cytokinesis. Immunocytochemistry revealed that micronuclei contain, at high frequencies, CREST antibody-reactive kinetochores, indicating the presence of whole chromosomes or centric fragments in these structures. Moreover, transmission electron microscopy showed that micronuclei exhibit ultrastructural details typical of interphase nuclei. Specifically, micronuclei exhibited morphological evidence of a nuclear lamina and segregation of karyoplasm into euchromatic and heterochromatic regions. All micronuclei examined were enclosed by a nuclear envelope of normal morphology and showed nuclear pore complexes. Together the findings provide evidence that DES interferes with the mitotic apparatus as early as prophase, resulting in the formation of micronuclei and, as a consequence, in the loss of chromatids or chromosomes. PMID- 1898764 TI - Sgs-3 chromatin structure and trans-activators: developmental and ecdysone induction of a glue enhancer-binding factor, GEBF-I, in Drosophila larvae. AB - The transcription of the Drosophila melanogaster 68C salivary gland glue gene Sgs 3 involves the interaction of a distal and a proximal regulatory region. These are marked in vivo by a specific chromatin structure which is established sequentially during development, starting early in embryogenesis. The distal region is characterized by a stage- and tissue-specific DNase I hypersensitive site. A stage- and tissue-specific factor, GEBF-I, binds in this region and is missing in 2B5 mutant larvae which lack Sgs-3 transcripts. This binding involves the simultaneous interaction with two distinct DNA sequences which induces conformational changes in the protein. Salivary glands acquire competence to respond to ecdysone in the mid-third larval instar, whereafter the hormone rapidly induces both the GEBF-I protein and Sgs-3 transcription. PMID- 1898766 TI - Potentiation by caffeine of the frequencies of micronuclei induced by mitomycin C and cyclophosphamide in young mice. AB - Employing the micronucleus test in mouse bone marrow and in fetal mouse liver, the possible clastogenicity of caffeine as well as its influence on MMC- and CP induced micronucleus levels were studied. The treatment of male and female C57Bl or BDF1 (C57Bl x DBA2) mice with caffeine (1 or 3 x 50 mg/kg and 100 mg/kg, s.c.) had no clastogenic effect in mouse bone marrow or in the fetal livers and maternal bone marrow when pregnant mice were injected with caffeine on day 16-17 of gestation. MMC (2.0 mg/kg, i.p.) increased up to 10-30-fold the number of MNPCEs in bone marrow compared to a 3-7 fold elevation of MNPCEs in fetal liver. A similar effect was also established in pregnant mice treated with CP (30 mg/kg, i.p.). No significant sex differences in spontaneous and MMC- or CP-induced MNPCEs levels were established in C57Bl and BDF1 mice. However, a significantly higher spontaneous rate of MNPCEs as well as a better-expressed responsiveness to the clastogenic activity of MMC and CP were established in C57Bl compared to BDF1 mice. The pregnancy had no effect on MMC- or CP-induced clastogenicity although a tendency to a decreased sensitivity to the damaging activity of MMC seemed to be detected in pregnant C57Bl mice compared to virgin female animals. The combined treatment of mice with caffeine (3 x 100 mg/kg) and MMC or CP caused an up to 45 49% potentiation of clastogenesis in the bone marrow of male, female and pregnant female C57Bl and BDF1 mice but not in fetal mouse livers. PMID- 1898767 TI - 'Rec-lac test' for detecting SOS-inducing activity of environmental genotoxic substance. AB - beta-Galactosidase activities (beta-GA) of E. coli strains carrying the fusion gene of recA and lacZ, GE94 and its DNA repair-deficient derivatives such as KY946[uvrA], KY945[recA] and KY943[lexA] treated with UV, 4NQO, MNNG and MMC were examined. The beta-GA, reflecting the SOS-inducing activity, of GE94 and KY946 treated with these compounds increased significantly with a clear dose-response relationship, and reached a maximum level within 60 min, while no response was seen in KY945 and KY943. Using KY946 and KY945 as a positive and a negative indicator, respectively, the SOS-inducing activity of oxidative mutagens, i.e., hydrogen peroxide (H2O2), formaldehyde, tert-butyl hydroperoxide, cumene hydroperoxide and streptonigrin, was investigated. Clear dose-dependent increases in beta-GA were observed in KY946 treated with all oxidative mutagens tested, but not in KY945. Significant increases in beta-GA were observed with a lower concentration of H2O2 and a shorter incubation time of 4NQO in this assay than in the umu-test. The assay, called 'Rec-lac test' by us, may be useful to detect environmental genotoxic substances. PMID- 1898768 TI - Antimutagenicity studies of chlorophyllin using the Salmonella arabinose resistant assay system. AB - Studies with the arabinose-resistant Salmonella forward mutation assay system were performed to determine the antimutagenic activity of chlorophyllin against the mutagenic activity of aflatoxin B1 (AFB1), 2-aminoanthracene (2AA), benzo[a]pyrene (BaP), N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and solvent extracts of coal dust (CD), diesel emission particles (DE), airborne particles (AP), tobacco snuff (TS), black pepper (BP) and red wine (RW). Various concentrations of each chemical and complex mixture extract were assayed for mutagenic activity with and/or without S9 in a preincubation test. One concentration of each chemical and complex mixture extract was then tested with various concentrations of chlorophyllin. Results showed that chlorophyllin, at concentrations of 2.5 mg/plate or less, completely or almost completely inhibited the mutagenicity of 2AA, AFB1, BaP, MNNG and solvent extracts of CD, DE and RW. With concentrations from 1.25 to 5 mg/plate, chlorophyllin inhibited over 50% of the mutagenicity of AP, TS and BP extracts. These results further substantiate the antimutagenic efficacy of chlorophyllin against chemicals and complex mixtures. PMID- 1898769 TI - Treatment of tuberculosis in patients with advanced human immunodeficiency virus infection. AB - BACKGROUND AND METHODS: Infection with the human immunodeficiency virus (HIV) increases the risk of tuberculosis and may interfere with the effectiveness of antituberculosis chemotherapy. To examine the outcomes in patients with both diagnoses, we conducted a retrospective study of all 132 patients listed in both the acquired immunodeficiency syndrome (AIDS) and tuberculosis case registries in San Francisco from 1981 through 1988. RESULTS: At the time of the diagnosis of tuberculosis, 78 patients (59 percent) did not yet have a diagnosis of AIDS, 18 patients (14 percent) were given a concomitant diagnosis of AIDS (as determined by the presence of an AIDS-defining disease other than tuberculosis), and the remaining 36 patients (27 percent) already had AIDS. The manifestations of tuberculosis were entirely pulmonary in 50 patients (38 percent), entirely extrapulmonary in 40 patients (30 percent), and both pulmonary and extrapulmonary in 42 patients (32 percent). The treatment regimens were as follows: isoniazid and rifampin supplemented by ethambutol for the first two months, 52 patients; isoniazid and rifampin supplemented by pyrazinamide and ethambutol for the first two months, 39 patients; isoniazid and rifampin, 13 patients; isoniazid and rifampin supplemented by pyrazinamide for the first two months, 4 patients; and other drug regimens, 17 patients. The intended duration of treatment for patients whose regimen included pyrazinamide was six months, and for patients who did not receive pyrazinamide, nine months. Seven patients received no treatment because tuberculosis was first diagnosed after death. Sputum samples became clear of acid fast organisms after a median of 10 weeks of therapy. Abnormalities on all chest radiographs taken after three months of treatment were stable or improved except for those of patients who had new nontuberculous infections. The only treatment failure occurred in a man infected with multiple drug-resistant organisms who did not comply with therapy. Adverse drug reactions occurred in 23 patients (18 percent). For all 125 treated patients, median survival was 16 months from the diagnosis of tuberculosis. Tuberculosis was a major contributor to death in 5 of the 7 untreated patients and 8 of the 125 treated patients. Three of 58 patients who completed therapy had a relapse (5 percent); compliance was poor in all 3. CONCLUSIONS: Tuberculosis causes substantial mortality in patients with advanced HIV infection. In patients who comply with the regimen, conventional therapy results in rapid sterilization of sputum, radiographic improvement, and low rates of relapse. PMID- 1898770 TI - Phenytoin for the prevention of post-traumatic seizures. PMID- 1898771 TI - The GTPase superfamily: conserved structure and molecular mechanism. AB - GTPases are conserved molecular switches, built according to a common structural design. Rapidly accruing knowledge of individual GTPases--crystal structures, biochemical properties, or results of molecular genetic experiments--support and generate hypotheses relating structure to function in other members of the diverse family of GTPases. PMID- 1898772 TI - Base sequence discrimination by zinc-finger DNA-binding domains. AB - Zinc fingers constitute important eukaryotic DNA-binding domains, being present in many transcription factors. The Cys2/His2 zinc-finger class has conserved motifs of 28-30 amino acids which are usually present as tandem repeats. The structure of a Cys2/His2 zinc finger has been determined by nuclear magnetic resonance, but details of its interaction with DNA were not established. Here we identify amino acids governing DNA-binding specificity using in vitro directed mutagenesis guided by similarities between the zinc fingers of transcription factors Sp1 and Krox-20. Krox-20 is a serum-inducible transcription activator which is possibly involved in the regulation of hindbrain development; it contains three zinc fingers similar to those of Sp1 and binds to a 9-base-pair target sequence which is related to that of Sp1. Our results show that each finger spans three nucleotides and indicate two positions in Krox-20 zinc fingers that are important for base-pair selectivity. Modelling with molecular graphics suggests that these residues could bind directly with the bases and that other amino acid-base contacts are also possible. PMID- 1898774 TI - Cloning and sequencing of Octopus dofleini hemocyanin cDNA: derived sequences of functional units Ode and Odf. AB - A number of additional cDNA clones coding for portions of the very large polypeptide chain of Octopus dofleini hemocyanin were isolated and sequenced. These data reveal two very similar coding sequences, which we have denoted "A type" and "G-type." We have obtained complete A-type sequences coding for functional units Ode and Odf; consequently a total of three such unit sequences are now known from a single subunit of one molluscan hemocyanin. This presents the opportunity to make sequence comparisons within one hemocyanin subunit. Domains within one subunit show on the average 42% identity in amino acid residues; corresponding functional units from hemocyanins of different species show degrees of identity of 53-75%. Therefore, molluscan hemocyanins already existed before the individual molluscan classes diverged in the early Cambrian. Sequence comparisons of molluscan hemocyanins with arthropodan hemocyanins and tyrosinases allow us to identify the ligands of the "Copper B" site with high probability. Possible ligands for the "Copper A" site are proposed, based on sequence comparisons between molluscan hemocyanins and tyrosinases. Besides two histidine side chains, a methionine side chain might be involved in binding of Copper A, a result not in conflict with spectroscopic studies. PMID- 1898773 TI - Synergistic transcriptional enhancement does not depend on the number of acidic activation domains bound to the promoter. AB - Many eukaryotic transcriptional activator proteins contain a DNA-binding domain that interacts with specific promoter sequences and an acidic activation region that is required to stimulate transcription. Transcriptional enhancement by such activator proteins is often synergistic and promiscuous; promoters containing multiple binding sites for an individual protein or even for unrelated proteins can be 10-100 times more active than promoters with single sites. It has been suggested that such synergy reflects a nonlinear response of the basic transcription machinery to the number and/or quality of acidic activation regions. Here, we determine the transcriptional activity of Jun-Fos heterodimers containing one or two GCN4 acidic activation regions on promoters containing one or two Ap-1 target sites. Surprisingly, heterodimers with one or two acidic regions activate transcription with similar efficiency and are equally synergistic (10- to 15-fold) on promoters containing two target sites. Thus, transcriptional synergy does not depend on the number of acidic activation regions but rather on the number of proteins bound to the promoter. This suggests that synergy is mediated either by cooperative DNA binding or by alternative mechanisms in which the DNA-binding domain plays a more direct role in transcription (e.g., changes in DNA structure, nucleosome displacement, or direct interactions with the transcriptional machinery). PMID- 1898775 TI - The Polycomb protein shares a homologous domain with a heterochromatin-associated protein of Drosophila. AB - The Polycomb (Pc) gene of Drosophila melanogaster is a member of a large class of genes (Pc group) required for the segment-specific repression of homeotic selector genes. Mutations in Pc-group genes show strong posterior transformations in homozygous embryos resulting from an ectopic expression of homeotic genes in segments where they are not supposed to be active. Genetic evidence suggests that Pc is part of a cellular memory mechanism responsible for the transmission of the homeotic expression pattern through developmental time. We have determined the nucleotide sequence for the genomic DNA of the Pc gene and for cDNAs corresponding to the 2.5-kilobase Pc mRNA. The deduced sequence of the Pc protein exhibits a homology to the heterochromatin-associated protein HP1 encoded by the suppressor of position effect variegation gene Su(var) 205. The homology is confined to a 37-amino acid domain in the N-terminal part of the two proteins. Our findings extend to the molecule level the genetically identified parallels between the Pc-group genes and the modifiers of position effect variegation. This suggests that Pc could use analogous mechanisms at the level of the higher order chromatin structure for the stable transmission of a determined state, as has been proposed for the clonal propagation of heterochromatin domains. PMID- 1898776 TI - Membrane-binding domain of the small G protein G25K contains an S-(all-trans geranylgeranyl)cysteine methyl ester at its carboxyl terminus. AB - We showed previously that a 23-kDa guanine nucleotide-binding protein (G protein) purified from bovine brain membranes is carboxyl methylated and that this modification occurs at or near the membrane-binding domain. In the present study, we identified this small G protein as G25K (formerly termed Gp). We demonstrated that proteolytic digests of 3H-methylated G25K contained radiolabeled material that coeluted with synthetic S-(geranylgeranyl)cysteine methyl ester on reversed phase HPLC. Further treatment by performic acid oxidation yielded radiolabeled material that coeluted with L-cysteic acid methyl ester, verifying that the isoprenoid moiety and carboxyl methyl ester are localized on a C-terminal cysteine residue. Analysis by gas chromatography-coupled mass spectrometry of material released from purified G25K by Raney nickel treatment positively identified the covalently bound lipid as an all-trans-geranylgeranyl (C20) isoprenoid moiety. These results suggest that geranylgeranyl modification and perhaps methyl esterification function in the membrane localization of this small G protein. PMID- 1898777 TI - Interleukin 1 regulates heparin-binding growth factor 2 gene expression in vascular smooth muscle cells. AB - The angiogenic polypeptide heparin-binding growth factor 2 (HBGF-2), or basic fibroblast growth factor, is a mitogen for vascular smooth muscle cells in vitro and in vivo. Smooth muscle cells also synthesize HBGF-2; thus, it may stimulate their proliferation in vivo by both autocrine and paracrine mechanisms. We report here that HBGF-2 gene expression in human saphenous vein smooth muscle cells is induced by interleukin (IL)-1 alpha and IL-1 beta, inflammatory cytokines produced by many cell types in response to a variety of signals. Maximal HBGF-2 mRNA levels are detected 2-4 hr after IL-1 treatment; induction may require de novo protein synthesis and does not occur if transcription is inhibited. Immunoprecipitation analysis indicates that IL-1-stimulated cells also express an increased amount of HBGF-2 protein. Interferon gamma and glucocorticoids, inhibitors of smooth muscle cell proliferation in vitro and in vivo, suppress the induction of HBGF-2 expression by IL-1. These results imply that cytokines released at sites of vascular injury or inflammation may regulate HBGF-2 production by smooth muscle cells. Increased HBGF-2 levels within the vessel wall could play a role in both the smooth muscle cell proliferation and the neovascularization associated with the development of atherosclerotic lesions. PMID- 1898778 TI - A mutagenesis study of a catalytic antibody. AB - We have generated seven site-specific mutations in the genes encoding the variable region of the heavy chain domain (VH) of the phosphocholine-binding antibody S107. S107 is a member of a family of well-characterized highly homologous antibodies that bind phosphorylcholine mono- and diesters. Two of these antibodies, MOPC-167 and T15, have previously been shown to catalyze the hydrolysis of 4-nitrophenyl N-trimethylammonioethyl carbonate. Two conserved heavy-chain residues, Tyr-33 and Arg-52, were postulated to be involved in binding and hydrolysis of 4-nitrophenylcholine carbonate esters. To more precisely define the catalytic roles of these residues, three Arg-52 mutants (R52K, R52Q, R52C) and four Tyr-33 mutants (Y33H, Y33F, Y33E, Y33D) of antibody S107 were generated. The genes encoding the VH binding domain of S107 were inserted into plasmid pUC-fl, and in vitro mutagenesis was performed. The wild type and mutant S107 antibodies were expressed in P-3X63-Ag8.653 (P-3) myeloma cells by using a modified SV2 shuttle vector. The catalytic properties of wild type antibody S107 are similar to those of the phosphocholine-specific antibody T15, which has the same VH protein sequence. In general, mutations at Tyr-33 had little effect on catalytic activity, whereas mutations at Arg-52 that result in loss of the positively charged side chain significantly lower the catalytic activity of S107. One mutant, Y33H, catalyzed the hydrolysis of 4-nitrophenyl N trimethylammonioethyl carbonate with a kcat of 5.7 min-1 and a Km of 1.6 mM at pH 7.5. These results not only demonstrate the importance of electrostatic interactions in catalysis by antibody S107 but also show that catalytic side chains can be introduced into antibodies to enhance their catalytic efficiency. PMID- 1898779 TI - Binding of small acid-soluble spore proteins from Bacillus subtilis changes the conformation of DNA from B to A. AB - Small acid-soluble spore proteins (SASPs) appear 3-4 hr after the onset of sporulation in Gram-positive bacteria and constitute up to 20% of the protein of mature spores. Previous studies using Bacillus subtilis deletion mutants lacking SASP-alpha and -beta have shown that such mutations abolish the elevated resistance of spores to UV radiation. Analyses using circular dichroism and Fourier-transform infrared spectroscopy now demonstrate that binding alpha/beta type SASPs to DNA in vitro causes a structural change in DNA, from the B to the A conformation. This may provide the basis whereby alpha/beta-type SASPs confer increased spore UV resistance in vivo--by changing spore DNA conformation, they alter DNA photochemistry such that UV irradiation produces spore photoproduct instead of the more lethal cyclobutane-type thymine dimers. PMID- 1898780 TI - Modulation of restriction enzyme-induced damage by chemicals that interfere with cellular responses to DNA damage: a cytogenetic and pulsed-field gel analysis. AB - The electroporation of restriction enzymes into mammalian cells results in DNA double-strand breaks that can lead to chromosome aberrations. Four chemicals known to interfere with cellular responses to DNA damage were investigated for their effects on chromosome aberrations induced by AluI and Sau3AI; in addition, the number of DNA double-strand breaks at various times after enzyme treatment was determined by pulsed-field gel electrophoresis (PFGE). The poly(ADP-ribose) polymerase inhibitor 3-aminobenzamide (3AB) dramatically increased the yield of exchanges and deletions and caused a small but transitory increase in the yield of double-strand breaks induced by the enzymes. 1-beta-D Arabinofuranosylcytosine, which can inhibit DNA repair either by direct action on DNA polymerases alpha and delta or by incorporation into DNA, potentiated aberration induction but to a lesser extent than 3AB and did not affect the amount of DNA double-strand breakage. Aphidicolin, which inhibits polymerases alpha and delta, had no effect on AluI-induced aberrations but did increase the aberration yield induced by Sau3AI. The postreplication repair inhibitor caffeine had no effect on aberration yields induced by either enzyme. Neither aphidicolin nor caffeine modulated the amount of DNA double-strand breakage as measured by PFGE. These data implicate poly(ADP-ribosyl)ation and polymerases alpha and delta as important components of the cellular processes required for the normal repair of DNA double-strand breaks with blunt or cohesive ends. Comparison of these data with the effect of inhibitors on the frequency of X-ray-induced aberrations leads us to the conclusion that X-ray-induced aberrations can result from the misjoining or nonrejoining of double-strand breaks, particularly breaks with cohesive ends, but that this process accounts for only a portion of the induced aberrations. PMID- 1898782 TI - Whole animal cell sorting of Drosophila embryos. AB - Use of primary culture cells has been limited by the inability to purify most types of cells, particularly cells from early developmental stages. In whole animal cell sorting (WACS), live cells derived from animals harboring a lacZ transgene are purified according to their level of beta-galactosidase expression with a fluorogenic beta-galactosidase substrate and fluorescence-activated cell sorting. With WACS, incipient posterior compartment cells that express the engrailed gene were purified from early Drosophila embryos. Neuronal precursor cells were also purified, and they differentiated into neurons with high efficiency in culture. Because there are many lacZ strains, it may be possible to purify most types of Drosophila cells. The same approach is also applicable to other organisms for which germ-line transformation is possible. PMID- 1898783 TI - Gemfibrozil: interaction with glyburide. PMID- 1898781 TI - The influence of exogenous eicosanoids on the radiation response of cultured bovine aortic endothelial cells. AB - The radioprotection by several eicosanoids was investigated in cultures of bovine aortic endothelial cells. One hour before irradiation (0-500 cGy, 137Cs gamma rays) 10 micrograms/ml of PGD2, PGE1, PGI2, misoprostol (PGE1-analog), 16,16 dimethyl PGE2, PGA2, or 1 microgram/ml LTC4 was added. Radiation decreased incorporation of [3H]thymidine at 4 h, cell number/culture at 24 h, and cell survival as measured by colony formation. Under these conditions the eicosanoids were not radioprotective. Two eicosanoids, PGD2 and PGA2, appeared to be toxic. Because receptors might mediate eicosanoid-induced radioprotection, radioligand binding of PGE2 and LTC4 and levels of adenosine 3',5'-cyclic monophosphate (cAMP) were measured. Evidence for a receptor was equivocal; there was nonspecific binding and metabolism of LTC4. The level of cAMP was elevated by 16 16-dimethyl-PGE2 in the presence of isobutyl methylxanthine; however, this combination of the prostaglandin and the methylxanthine was not radioprotective. These investigations suggest that an elevated cAMP level alone does not lead to eicosanoid-induced radioprotection of bovine aortic endothelial cell monolayers in vitro. PMID- 1898784 TI - Storage of saline-adenine-glucose-mannitol-suspended red cells in a new plastic container: polyvinylchloride plasticized with butyryl-n-trihexyl-citrate. AB - Blood collection and component preparation have been performed in integrally connected multiple plastic containers made with a new plastic. This polyvinylchloride (PVC) container plasticized with butyryl-n-trihexyl-citrate (BTHC) is a new material for blood storage; it contains no di(2 ethylhexyl)phthalate (DEHP). After removal of plasma and buffy coat, the red cells were suspended in saline-adenine-glucose-mannitol (SAGM) medium. After 42 day refrigerator storage, the total adenine nucleotide concentration remained the same as the initial concentration in the red cells, whereas ATP levels had decreased to 61 percent of the initial value. The 2,3 DPG concentration was 62 percent of normal on Day 7 and 21 percent on Day 14. Glucose consumption, lactate production, potassium leakage from red cells, and pH levels were similar to those found after storage in DEHP-plasticized containers under the same conditions. After 42 days, hemolysis levels were 0.56 +/- 0.21 percent and 0.42 +/- 0.17 percent in two series of units mixed weekly and 0.70 +/- 0.27 percent in units stored unmixed. Although even higher levels of hemolysis were observed in the units stored unmixed and used for 24-hour posttransfusion survival, the autologous red cell recovery results were excellent (83.2 +/- 5.1%, n = 8). BTHC plasticized PVC is found to be a suitable material for 42-day storage of red cells in SAGM solution. PMID- 1898785 TI - Postthaw stability of fibrinogen in cryoprecipitate stored between 1 and 6 degrees C. AB - The fibrinogen activity in thawed cryoprecipitate stored between 1 and 6 degrees C is maintained essentially unchanged in most bags for a month. Occasionally, a bag will have a reduction in fibrinogen. If pooling has not occurred, thawed cryoprecipitate should be useful as a source of fibrinogen for a period of time considerably in excess of the 6 hours allowed for its use as a source of factor VIII or von Willebrand factor. PMID- 1898786 TI - Inactivation of human immunodeficiency virus by gamma radiation and its effect on plasma and coagulation factors. AB - The inactivation of HIV by gamma-radiation was studied in frozen and liquid plasma; a reduction of the virus titer of 5 to 6 logs was achieved at doses of 5 to 10 Mrad at -80 degrees C and 2.5 Mrad at 15 degrees C. The effect of irradiation on the biologic activity of a number of coagulation factors in plasma and in lyophilized concentrates of factor VIII (FVIII) and prothrombin complex was examined. A recovery of 85 percent of the biologic activity of therapeutic components present in frozen plasma and in lyophilized coagulation factor concentrates was reached at radiation doses as low as 1.5 and 0.5 Mrad, respectively. As derived from the first-order radiation inactivation curves, the radiosensitive target size of HIV was estimated to be 1 to 3 MDa; the target size of FVIII was estimated to be 130 to 160 kDa. Gamma radiation must be disregarded as a method for the sterilization of plasma and plasma-derived products, because of the low reduction of virus infectivity at radiation doses that still give acceptable recovery of biologic activity of plasma components. PMID- 1898787 TI - Hemolytic disease of the newborn caused by anti-Rh32 and demonstration that RN encodes rhi (Ce,Rh7). AB - A family is described in which the mother made anti-Rh32 as a result of pregnancy; her second liveborn child had hemolytic disease of the newborn and required an exchange transfusion. In investigating the family, it was found that the father's RN gene did not make rhi and that his second Rh gene made normal amounts of c and e but a reduced amount of f. In the two children of the couple, who inherited a normal r or Ro from their mother, the paternally derived RN encoded an amount of rhi that could be detected in direct typing tests. In the father, lack of production of rhi by RN may have represented a suppressive effect of the ce(f) gene in trans to RN or the presence of an unlinked suppressor of Rh that might also have been responsible for the reduced production of f by his r or Ro gene. The two children in this family are the first persons in whom RN has been shown to make rhi. PMID- 1898788 TI - Identification of recipients with hepatitis C and other transfusion-transmitted infections: we can do better than look-back! PMID- 1898789 TI - Let's look back for hepatitis C virus-infected patients. PMID- 1898790 TI - Look-back at blood donors implicated in posttransfusion hepatitis (PTH) PMID- 1898791 TI - Benjamin Felson lecture. Chronic interstitial lung disease of unknown cause: a new classification based on pathogenesis. AB - Chronic interstitial lung disease of unknown cause is usually classified on the basis of descriptive histology. In this lecture, a recently published series of 910 cases of chronic interstitial lung disease is used to show that these descriptive terms can be reorganized into a classification that is based on inflammatory and neoplastic processes. The proposed classification includes three major diagnostic categories, two of which are based on the chronic inflammatory response and a third that results from infiltration of the interstitial space by neoplastic cells of either a benign, borderline, or frankly malignant nature. An argument is presented that the steps involved in the development of the endstage of chronic interstitial lung disease are similar in all three groups. The advantage of this new classification is that it shifts the emphasis from descriptive terminology to pathogenesis, which provides a more critical basis for investigation of the causes of these diseases. PMID- 1898792 TI - Advances in contrast-enhanced MR imaging. Principles. PMID- 1898793 TI - Advances in contrast-enhanced MR imaging. Neurologic applications. PMID- 1898794 TI - Advances in contrast-enhanced MR imaging. Nonneurologic applications. PMID- 1898795 TI - Advances in contrast-enhanced MR imaging. Gastrointestinal contrast agents. PMID- 1898796 TI - The changing epidemiology of tuberculosis and other mycobacterial infections in the United States: implications for the radiologist. AB - Diseases consequent to infection with mycobacterial organisms, such as Mycobacterium tuberculosis and other mycobacterial species, remain a significant health problem in the United States. Over the past decade several new factors have amplified this problem, the most significant of which is the ongoing epidemic of infection with the human immunodeficiency virus. This review will discuss the changing epidemiology of mycobacterial disease and emphasize the significance of these changes to the radiologist. PMID- 1898797 TI - Value of sonography in monitoring the therapeutic response of mediastinal lymphoma: comparison with chest radiography and CT. AB - The aim of this retrospective study was to assess the diagnostic value of mediastinal sonography, compared with that of chest radiographs and CT, in the follow-up of patients with mediastinal lymphomas and in the prediction of clinical outcome. The sonograms, chest radiographs, and CT scans of 40 consecutive patients with Hodgkin (n = 29) and non-Hodgkin (n = 11) lymphoma obtained before and after completion of therapy were analyzed blindly and independently by three radiologists and compared with clinical outcome. Nine patients were treated with radiotherapy, 12 with chemotherapy, and 19 with combined therapy. Therapeutic response was assessed from all available clinical and biochemical findings as well as from the combined results of all imaging studies performed on further follow-up. The sonograms showed obvious changes in the size and echogenicity of the mediastinal lymphomas that corresponded closely with the response to therapy. Sonography showed complete regression of the lymphomas in 30 patients who had complete remission. In five patients with incomplete remission, sonographic diagnoses were correct. All lymph nodes, irrespective of size, detected with sonography after a phase of complete remission indicated recurrence (five patients). Sonographic findings corresponded with those of CT in 25 (81%) of 31 cases. Clinical outcome suggested that the sonographic findings were more reliable in the five cases in which CT and sonographic findings conflicted. Chest radiographs were inadequate for monitoring the response of mediastinal lymphomas to therapy; in 17 (43%) of 40 cases, a false impression was obtained of the extent and therapeutic response of mediastinal lymphomas. The results of this study indicate that sonography is clearly superior to chest radiographs and comparable to CT for monitoring patients with mediastinal lymphomas. PMID- 1898798 TI - Value of CT in determining the need for angiography when findings of mediastinal hemorrhage on chest radiographs are equivocal. AB - The role of CT in determining the need for angiography in patients with possible thoracic vascular injury resulting from blunt trauma is controversial. During a 24-month period, we prospectively evaluated the results of CT to screen 90 patients with a history of decelerating thoracic trauma for evidence of mediastinal hemorrhage or great vessel abnormality. All patients either had equivocally abnormal mediastinal contours on chest radiographs (64%) or had technically suboptimal chest radiographs owing to body habitus or restriction to the supine projection (36%). Patients with unequivocal signs of mediastinal hemorrhage on chest radiographs underwent immediate arteriography without prior CT. Thoracic CT was interpreted as normal in 63 (77%) patients and no further imaging was performed. Five patients had technically suboptimal CT studies, and CT scans were interpreted as equivocal in six. These 11 patients had normal arteriograms. Sixteen CT scans (18%) demonstrated evidence of mediastinal hemorrhage and/or great vessel contour abnormality. Four (27%) of 15 patients who underwent arteriography had injury to the great vessels. One patient refused to undergo angiography. In 11 patients with CT evidence of mediastinal hemorrhage, major vascular injury was not seen on arteriography. These results suggest a valuable role for CT in determining the need for arteriography to detect potential great vessel injury in patients with blunt decelerating thoracic trauma and equivocally abnormal mediastinal contours on chest radiographs. PMID- 1898799 TI - Pathogenesis of pulmonary edema during interleukin-2 therapy: correlation of chest radiographic and clinical findings in 54 patients. AB - The pathogenesis of pulmonary edema that occurs during interleukin-2 therapy has often been attributed to an increase in pulmonary capillary permeability. However, renal insufficiency, fluid overload, and hypotension also develop in many patients. These manifestations of systemic toxicity may contribute to the development of pulmonary edema during therapy. Understanding the cause of pulmonary edema during interleukin-2 therapy could directly affect patients' care. Therefore, we reviewed the chest radiographs and clinical course of 54 patients who received high-dose interleukin-2 therapy and lymphokine-activated killer cells for advanced carcinoma. The type, frequency, and course over time of pulmonary abnormalities were recorded and correlated with clinical measures of renal function, fluid status, and blood pressure. Focal or diffuse parenchymal lung opacities were found on radiographs in 43 (80%) of 54 patients. Findings of interstitial pulmonary edema were most common, occurring in 76% of patients. Weight gain, hypotension, and elevation of the serum creatinine level were not associated statistically with interstitial edema. Diffuse air-space disease developed in 20% of patients. Focal consolidation, which was associated with positive central venous catheter cultures (p less than .03), developed in 28% of patients. Pleural effusion occurred in 48% of patients and was associated with all types of parenchymal disease. These data suggest that the frequent development of pulmonary edema during interleukin-2 therapy is not due to renal insufficiency, fluid overload, or hypotension, but is more likely the result of an interleukin-2-related increase in pulmonary capillary permeability. PMID- 1898800 TI - Abnormalities of the breast caused by biopsy: spectrum of mammographic findings. AB - It is important for radiologists to be familiar with the spectrum of mammographic abnormalities caused by postbiopsy changes in the breast. Although many breast biopsies leave no residual abnormality, occasionally an atypical manifestation of a biopsy scar may produce a radiologic finding suspicious enough to mandate a biopsy. Problem-solving maneuvers recommended to increase confidence that a change is related to a recent biopsy include (1) skin markers; (2) comparison with preoperative films; (3) correlation with physical examination; (4) tailored mammographic views, including focal spot compression, magnification, and tangential views; and (5) postoperative and follow-up mammograms. PMID- 1898801 TI - Videofluoroscopy in elderly patients with aspiration: importance of evaluating both oral and pharyngeal stages of deglutition. AB - Oropharyngeal functional impairment increases with age so that radiologists frequently are asked to determine the cause of aspiration in elderly patients. Neuromuscular and cognitive impairment often make it difficult to perform and interpret videofluoroscopic deglutition examinations in these patients. We retrospectively reviewed the barium swallow examinations in 50 elderly patients (mean age, 87 years) who were known to aspirate. We looked for specific patterns of oropharyngeal dysfunction that resulted in bolus misdirection. Analysis revealed that aspiration was due to abnormalities of the oral stage in 23, pharyngeal stage in 10, and both stages in 17. Dysfunction in the oral stage was due to ingestion of large volumes or rapid acquisition rates in nine, failure of containment during processing (bolus manipulation) in 18, and dissociation of lingual delivery and swallowing initiation in the transitional phase in 13. Dysfunction in the pharyngeal stage was due to incomplete transport (bolus retention) in 21 and defective closure of the laryngeal vestibule in 11. No significant relationship between conditions known to cause oropharyngeal dysfunction (dementia, stroke, Parkinson disease, disuse deconditioning) and the specific pattern of dysfunction was identified. These results indicate that an accurate and valid assessment of oropharyngeal dysfunction in elderly patients with aspiration is possible if specific patterns of dysfunction are sought. Our study indicates the importance of evaluating the oral and pharyngeal stages of deglutition in elderly patients who aspirate. PMID- 1898803 TI - Radiologic detection of colonic neoplasms: benefits of a systems-analysis approach. PMID- 1898802 TI - Carcinoma of the esophagus: CT vs MR imaging in determining resectability. AB - MR imaging and CT were performed prospectively in 35 patients with esophageal carcinoma to determine the resectability of the primary tumors, because at our institution patients with resectable tumors have surgery regardless of the presence of distant metastases. Tumors with evidence of aortic or tracheobronchial invasion on MR or CT were considered to be unresectable. Tracheobronchial invasion was diagnosed when the tumor extended into the lumen of the airway, and aortic invasion was diagnosed when the triangular fat space between the esophagus, aorta, and spine adjacent to the primary tumor was obliterated. Two patients were excluded because of suboptimal MR images produced by motion artifacts. Pathologic proof was obtained from either surgery or autopsy in 31 patients. Of these, six patients (19%) had proved unresectable tumors (three aortic invasion and three tracheobronchial invasion). In all six cases, these features were correctly detected with both MR and CT. One patient had false positive findings on MR and CT. An indeterminate diagnosis was obtained with MR in three patients and with CT in four patients. These incorrect or indeterminate results were all related to the diagnosis of aortic invasion. No patient had a false-negative result. When indeterminate diagnoses were considered false positive, sensitivity, specificity, and accuracy for resectability were 100%, 84%, and 87%, respectively, for MR and 100%, 80%, and 84%, respectively, for CT. We conclude that MR and CT have nearly the same accuracy in predicting resectability of tumors in patients with esophageal carcinoma. PMID- 1898804 TI - Fatty infiltration of the liver: quantification with phase-contrast MR imaging at 1.5 T vs biopsy. AB - Quantification of hepatic fat content by application of MR phase-contrast imaging (Dixon method) at 1.5 T was compared with results of biopsy in 16 patients with a variety of liver abnormalities. Motion artifact was suppressed by employing six or eight averages of short TR in-phase (echo offset, 0 msec), out-of-phase (echo offset, 1.1 msec), and in-phase (echo offset, 2.2 msec) spin-echo pulse sequences. The 360 degree out-of-phase sequence was used to assess the impact of T2* decay on this method of estimating fat fraction. A standard two-echo long TR sequence also was obtained in all patients. Histologic preparations from the biopsy specimens were examined by a pathologist who had no knowledge of the MR results and were graded according to overall visual assessment as belonging to one of four categories of fat fraction. Results of the MR-calculated apparent fat fraction were compared directly with biopsy category and were also placed in MR fat fraction categories, allowing estimation of the statistical correlation between the biopsy and MR grading systems. Eight of eight patients with biopsy categories indicating a fat fraction of less than 0.25 were computed by MR to have a fat fraction of less than 0.1. Seven of eight patients with biopsy categories indicating a fat fraction of greater than 0.25 were computed by MR to have a fat fraction of at least 0.24. The MR-calculated apparent fat fraction category correlated significantly with the histologic biopsy category (r = .86, p less than .01). When compared with the in-phase image, decreased signal from liver was visually apparent on the 180 degree out-of-phase images in all cases in which the fat fraction was at least 0.24, but there was no indication of fatty liver on the standard T1- or T2-weighted images. Calculated T2 also showed no correlation with degree of fatty deposition. Correction for T2* decay by using the 360 degree out-of-phase acquisition in addition to the standard 0 degree and 180 degree out-of-phase images had little effect on fat fraction computation. Phase-contrast MR is a promising noninvasive method for quantitative assessment of fatty deposition in the liver. PMID- 1898805 TI - Periportal contrast enhancement on CT scans of the liver. AB - Periportal contrast enhancement relative to adjacent liver and portal blood has been reported on CT scans in cases of schistosomiasis and hepatic Kaposi sarcoma in AIDS patients. We observed this phenomenon in 10 (8%) of 130 consecutive, contrast-enhanced, nondynamic CT examinations of the abdomen. Thus, the occurrence is more common and less specific than previously reported. Seven of the 10 patients in our series were receiving chemotherapy for malignant disease, and three had abdominal pain with no definitive diagnosis. In four of the 10 patients, corresponding areas of periportal low attenuation or radiolucency were observed on initial dynamically enhanced scans. Periportal enhancement may be related to late diffusion of contrast material into periportal areas that were initially radiolucent. Such diffusion may occur because of endothelial insult. Periportal contrast enhancement appears to be a nonspecific finding on nondynamic contrast-enhanced CT scans of the abdomen. Periportal enhancement is important to recognize because it can mimic the appearance of portal vein thrombosis and may also be used to differentiate intrahepatic biliary dilatation from periportal radiolucency. PMID- 1898806 TI - Focal nodular hyperplasia of the liver: MR findings in 35 proved cases. AB - MR images of 28 patients with 35 lesions of hepatic focal nodular hyperplasia were reviewed to determine the frequency of findings considered typical of this condition (isointensity on T1- and T2-weighted pulse sequences, a central hyperintense scar on T2-weighted images, and homogeneous signal intensity). Fifteen lesions were imaged at 0.6 T with T1- and T2-weighted spin-echo (SE) pulse sequences; 20 lesions were imaged at 1.5 T with T1-weighted SE and gradient echo pulse sequences and T2-weighted SE pulse sequences. Diagnosis of focal nodular hyperplasia was made pathologically in 25 patients, with nuclear scintigraphy in four, and with follow-up imaging in six. Only seven lesions (20%) were isointense relative to normal liver on both T1- and T2-weighted images. On T1-weighted SE images, 21 lesions (60%) were isointense relative to normal liver, 12 (34%) were hypointense, and two (6%) were hyperintense. On T2-weighted SE images, 12 lesions (34%) were isointense and 23 (66%) were hyperintense relative to normal liver. A central scar was present in 17 lesions (49%) and was hypointense relative to the lesion on T1-weighted images and hyperintense on T2 weighted images. Twenty lesions (57%) were of homogeneous signal intensity throughout the lesion, except for the presence of a central scar. All three MR imaging characteristics were present in three cases (9%). We conclude that hepatic focal nodular hyperplasia has a wide range of signal intensity on MR imaging. PMID- 1898807 TI - Choledochal cysts: classification and cholangiographic appearance. AB - A classification scheme for choledochal cysts is outlined and their appearance on cholangiograms is illustrated. Choledochal cysts are uncommon anomalies of the biliary system and are probably congenital in origin. They are manifested by cystic dilatation of the extra- or intrahepatic biliary tree or both. The classification system described here divides choledochal cysts into one of five main types. The most common, which is manifested by cystic or focal segmental dilatation of the common bile duct or fusiform choledochal dilatation, accounts for 80-90% of cases. PMID- 1898808 TI - MR of the knee: the significance of high signal in the meniscus that does not clearly extend to the surface. AB - On MR images of the knee it is sometimes impossible to determine with confidence if a focus of high signal in the meniscus is confined to the substance of the meniscus or if it extends to involve the surface. This is a critical differentiation because the latter represents meniscal tears that can be found and treated at arthroscopy, whereas the former represents degeneration, tears, or perhaps normal variants that cannot be detected or treated arthroscopically. We make an equivocal diagnosis of a tear when it is difficult to decide if signal in a meniscus involves the meniscal surface. We studied MR scans of the knee in 142 consecutive patients for the presence of such equivocal tears. Their prevalence was 14% (20/142); 17 were in the posterior horn of the lateral meniscus and three were in the posterior horn of the medial meniscus. In 13 cases with arthroscopy/arthrotomy correlation, no tears were found. In one of the 20 patients in whom the meniscus was removed during arthroplasty, histologic examination of the meniscus showed separation of collagen bundles, which was caused by meniscal degeneration confined to the substance of the meniscus. These results suggest that a meniscal tear is unlikely when MR scans show a focus of high signal in a meniscus that does not unequivocally extend to involve the surface of the meniscus. PMID- 1898809 TI - Fournier gangrene caused by a perforated retroperitoneal appendix: CT demonstration. PMID- 1898810 TI - Two-piece wrist surface coil. PMID- 1898811 TI - Comparison of iohexol with barium in gastrointestinal studies of infants and children. AB - This study evaluates iohexol as a contrast agent in the gastrointestinal tract in children. In the first part of the study, iohexol in concentrations of 180 and 300 mg l/ml was compared in double-blind manner with barium. Sixty-four patients were studied. No significant difference in changes of blood pressure and pulse rate was found between the three groups of patients studied. Diarrhea was significantly more common in the children receiving iohexol than in children receiving barium. The diarrhea was not due to previously identified high-risk factors in the children, nor was it due to concurrent medication. When image quality was assessed in each anatomic region of the gastrointestinal tract, fewer nondiagnostic ratings occurred with barium than with iohexol. With barium, fewer ratings of poor mucosal coating and slightly fewer ratings of suboptimal contrast density occurred. The second part of the study was an open evaluation of iohexol 180 mg l/ml in 18 patients in whom barium was clinically contraindicated. Three of 53 assessments were nondiagnostic. Mucosal coating was poor in 6%, and contrast density was suboptimal in 8% of patients. The results of this study indicate that barium is the preferred contrast agent for routine evaluation of the gastrointestinal tract in children. Good-quality images can be obtained, however, with iohexol in concentrations of 180 or 300 mg l/ml, and iohexol is an excellent contrast agent for evaluation of the gastrointestinal tract in those patients in whom barium is relatively or absolutely contraindicated. PMID- 1898812 TI - Calcification of the ligamentum arteriosum in children: a normal finding on CT. AB - Calcification of the ligamentum arteriosum is a rare finding on plain radiographs. We commonly have seen the calcification on unenhanced CT scans of the chest, a finding not previously reported. A retrospective review of unenhanced CT scans of the chest was undertaken to determine the frequency of the described finding. Seven (13%) of 53 patients had a well-demarcated focus of calcification in the region of the ligamentum arteriosum. None of these patients had evidence of a patent ductus arteriosum. Calcification within the ligamentum arteriosum was seen in 13% of routine CT examinations of the chest in children and should not be confused with a pathologic process producing mediastinal calcifications. PMID- 1898813 TI - Radiologic evaluation of limb-lengthening procedures. AB - Limb-lengthening procedures are being performed at an increasing rate in the United States. A successful outcome relies heavily on serial radiologic evaluation. Therefore, it is important for radiologists to become familiar with the various techniques, their normal radiologic appearance, and associated complications. Lengthening by the Wagner method, distraction epiphysiolysis, and the Ilizarov technique are illustrated. Chondrodiatasis and callotasis also are discussed. PMID- 1898814 TI - Unilateral hydrocephalus: prenatal sonographic diagnosis. AB - We studied six cases of unilateral hydrocephalus detected prenatally to analyze the sonographic features of the abnormality and to determine the cause and clinical outcome. In all cases, third-trimester sonograms showed marked unilateral lateral ventriculomegaly (mean atrial width, 4.4 cm) and normal contralateral lateral, third, and fourth ventricles. Five of the six cases had marked thinning of the cortical mantle on the affected side and shift of midline structures to the contralateral side. The causes of unilateral hydrocephalus were agenesis or stenosis of the foramen of Monro in three cases, transient obstruction of the foramen in one fetus with an intraventricular hematoma, underlying brain dysplasia in one fetus with a variant of holoprosencephaly, and undetermined in one case. All six neonates had placement of a ventriculoperitoneal shunt catheter; four of these have had normal cognitive development at follow-up. The remaining two infants have moderate to severe developmental impairment. Unilateral hydrocephalus is a rare anomaly that can be recognized by prenatal sonography. Even though unilateral ventriculomegaly may be marked, early diagnosis and treatment may result in a favorable clinical outcome. PMID- 1898815 TI - Occult ectopic ureter in girls with urinary incontinence: diagnosis by using CT. PMID- 1898816 TI - Limited-slice CT in the evaluation of paranasal sinus disease in children. PMID- 1898817 TI - CT measurement of the tracheal lumen in children and adolescents. PMID- 1898818 TI - Intracranial vascular abnormalities: value of MR phase imaging to distinguish thrombus from flowing blood. AB - The interpretation of conventional spin-echo and gradient-echo MR images of intracranial vascular lesions can be complex and ambiguous owing to variable effects on image intensity caused by flowing blood or thrombus. MR phase images, obtained simultaneously with conventional-magnitude images, are useful for evaluating proton motion (i.e., blood flow), and therefore can simplify the diagnosis of the presence or absence of thrombosis within a vascular structure or lesion. Fourteen patients with a variety of intracranial vascular abnormalities (aneurysms, superior sagittal sinus thrombosis, neoplasms adjacent to venous sinuses, and vascular malformations) were evaluated with conventional MR and phase imaging for the presence of blood flow. The phase images correlated with angiography in all cases. Phase imaging was not necessarily better than conventional spin-echo imaging in all cases, but it simplified the evaluation of thrombus vs blood flow in many. In three of five aneurysms, the phase images were diagnostic for evaluating lumen patency whereas the conventional images were ambiguous. Phase imaging was advantageous for detecting tumor invasion of the venous sinus when venous blood was enhanced by gadopentetate dimeglumine. A laminar flow phantom experiment determined the lower limits of sensitivity of phase imaging to be 0.5 cm/sec in the slice-select and 2.5 cm/sec in the read gradient directions. Phase imaging is a simple, reliable technique that can distinguish thrombosis from flowing blood within intracranial lesions. It is easily performed and adds no additional time to the MR examination. PMID- 1898819 TI - Paranasal sinuses on MR images of the brain: significance of mucosal thickening. AB - One hundred twenty-eight patients were examined prospectively to determine the significance of mucosal thickening seen in the paranasal sinuses during routine MR imaging of the brain. On the basis of responses to a questionnaire, each patient was categorized as symptomatic (n = 60) or asymptomatic (n = 68) for paranasal sinus disease. Patients were categorized further on the basis of the maximal mucosal thickening seen by MR in any paranasal sinus. A modified t test was used to compare the prevalence of various degrees of mucosal thickening between symptomatic and asymptomatic groups. Statistically significant differences between the groups were seen only in those patients with normal sinuses and in those with 4 mm or more of mucosal thickening. We conclude that mucosal thickening of up to 3 mm is common and lacks clinical significance in asymptomatic patients. An ancillary finding is that 1- to 2-mm areas of mucosal thickening in the ethmoidal sinuses occur in 63% of asymptomatic patients. This minimal mucosal thickening in the ethmoidal sinuses is thought to be a normal variant, possibly a function of the physiologic nasal cycle. PMID- 1898820 TI - Angiography is useful in detecting the source of chronic gastrointestinal bleeding of obscure origin. AB - The treatment of patients with chronic gastrointestinal bleeding can be a frustrating diagnostic challenge. In the past 10-15 years, a variety of new diagnostic procedures (e.g., fiber-optic endoscopy, scintigraphy, and double contrast barium studies) have become available to examine these patients. Despite these new procedures, a small number of patients continue to bleed without a defined cause. We sought to evaluate the role of visceral angiography in patients with chronic gastrointestinal bleeding in whom findings on an extensive noninvasive workup have been normal. Between 1983 and 1990, we obtained angiograms on 36 such patients. The cause of bleeding was established by angiography in 16 patients (44%). In 11 of these 16, angiography revealed only a structural abnormality without active bleeding. Twenty patients had normal angiographic findings. No angiograms were false-positive, but three were false negative (8%). No complication occurred as a result of the angiographic procedures. Our experience shows that visceral angiography can provide a positive diagnosis in a significant number of patients with chronic gastrointestinal bleeding of obscure origin in whom all other diagnostic measures have been unrevealing. Despite improvements in noninvasive diagnostic techniques, angiography still remains an important tool for examining this group of patients. PMID- 1898821 TI - CT analysis of a safe approach for translumbar access to the aorta and inferior vena cava. PMID- 1898822 TI - A new percutaneous access set for interventional procedures. PMID- 1898823 TI - Improved needle-tip visualization by color Doppler sonography. PMID- 1898824 TI - Music enhances patients' comfort during MR imaging. PMID- 1898825 TI - Reaction to intrathecal iohexol. PMID- 1898826 TI - Pneumoperitoneum and catamenial pneumothorax. PMID- 1898827 TI - A different opinion on the Tru-Close Thoracic Vent. PMID- 1898828 TI - Papillomatosis of the common bile duct associated with ampullary carcinoma. PMID- 1898829 TI - Scintigraphic detection of splenosis causing ureteral compression and hydronephrosis. PMID- 1898831 TI - Bone scintigraphy for evaluation of pelvic pain. PMID- 1898830 TI - Detection of inadvertent vaginal filling during cystography. PMID- 1898832 TI - An uncommon complication of translumbar aortography. PMID- 1898833 TI - Doppler velocity waveforms of blood flow in the fetal renal artery in a case of Meckel syndrome. PMID- 1898834 TI - Increased serum osteocalcin levels in patients with lactase deficiency. AB - Serum levels of osteocalcin, a noncollagenous bone matrix protein, have been found to be a specific biochemical parameter of bone formation. In the literature in subjects with osteoporosis, an increased incidence of lactase deficiency has been described. We therefore determined the serum levels of osteocalcin in 10 patients with lactase deficiency and in 20 control subjects by radioimmunoassay. The patients with lactase deficiency were dietary treated and had a very low daily calcium intake. Serum osteocalcin levels were significantly higher in the patients with lactase deficiency than in the control subjects. In contrast, serum levels of parathyroid hormone, alkaline phosphatase, calcium, and phosphorus were not statistically different in the two groups. Our data suggest an increased rate of bone turnover in patients with lactase deficiency on a low calcium diet; possibly calcium supplementation is indicated in dietary-treated patients with lactase deficiency. PMID- 1898835 TI - Cardiovascular collapse following orthoclone OKT3 administration: a case report. AB - Orthoclone OKT3 has been described to have significant adverse effects on the cardiovascular system, including pulmonary edema, angina, dysrhythmias, hypertension, and hypotension, usually following the first or second doses of the drug. We describe a case of cardiopulmonary arrest in a patient 1 minute after the initial injection of OKT3. Two subsequent doses were successfully administered with the guidance of hemodynamic monitoring, which showed profound, immediate effects of OKT3 on the cardiovascular system. Potential mechanisms of these effects are discussed. PMID- 1898836 TI - Recombinant human erythropoietin: factors to consider in cost-benefit analysis. PMID- 1898837 TI - Formula contamination as a potential cause of diarrhea in tube-fed patients. PMID- 1898839 TI - Low-risk cesarean section prophylaxis issue still unsettled. PMID- 1898838 TI - Lupus anticoagulant inhibition of in vitro prostacyclin release is associated with a thrombosis-prone subset of patients. AB - PURPOSE: The effect of lupus anticoagulant-containing sera on endothelial prostacyclin generation (both basal and after thrombin stimulation) was determined. Subsets of patients who had experienced arterial, venous, or no thrombosis were compared with respect to the quantitation of antiphospholipid antibody and effects on prostacyclin production. PATIENTS AND METHODS: Serum antiphospholipid antibodies were detected in 26 patients by immunologic (enzyme linked immunosorbent assay) and kinetic (anticoagulant) assays. Cultured human endothelial cells were exposed to patient or normal serum, and the release of prostacyclin was determined by radioimmunoassay of supernatants. Release was determined in the absence and presence of the secretagogue, thrombin (1 U/mL), corrected for interassay variation, and correlated with other clinical and laboratory variables. RESULTS: The normal prostacyclin response was a 2.5-fold increase after thrombin (1 U/mL) compared to basal production. Patients with a history of arterial thrombosis (Group 1, n = 10) had the highest IgG anticardiolipin antibody titers (449 +/- 115 [OD x 1,000]), most prolonged kaolin clotting times (140 +/- 15 seconds), and the least prostacyclin response to thrombin (1.36-fold). Patients with venous thrombosis (Group 2, n = 6) had lower titers (329 +/- 120), intermediate clotting times (125 +/- 19 seconds), and slightly impaired prostacyclin responses (2.18-fold). Patients with no history of thrombosis (Group 3, n = 10) had low antibody titers (220 +/- 20), mildly prolonged clotting times (108 +/- 6 seconds), and normal prostacyclin responses (2.33-fold). Patient serum did not alter basal or arachidonate-induced prostacyclin production. Group 1 had significantly lower platelet counts (99 +/- 19) compared to Group 2 (167 +/- 35) or Group 3 (167 +/- 34), but were similar in age and associated diagnoses. CONCLUSIONS: Inhibition of prostacyclin responses is commonly found in serum from patients with lupus anticoagulants, and is likely to be present in patients with high IgG anticardiolipin antibodies, strong lupus anticoagulants, low platelet counts, and a recent arterial thrombosis. PMID- 1898840 TI - Halothane potentiates the antitumor activity of gamma-interferon and mimics calmodulin-blocking agents. AB - This study reports effects of halothane on tumor cells in vitro. Cells from the human colon cancer cell line HT-29 were exposed to various concentrations of halothane for 8-72 h. The effect of this exposure on this colon cancer cell line, with and without coincubation with the biologic response modifier gamma interferon (IFN-gamma), was studied. Using the tumor target cell survival (TTCS) assay, concentrations of halothane from 0.5 to 2% markedly augmented the antitumor activities of IFN-gamma against HT-29. The tumor cell cytostatic effects of IFN-gamma in the 0.75-6-unit/ml range were increased nearly 400% by concentrations of halothane as low as 1%. These results were confirmed in a separate cytolytic assay (Indium-111 release assay), which revealed that halothane concentrations in the 2-4% range markedly increased the cytolytic capacity of IFN-gamma at doses of IFN-gamma between 75 and 1,250 units/ml. The cytolytic activity of IFN-gamma was increased nearly 300% by doses of halothane as low as 1%. A nearly identical pattern of augmentation of IFN-gamma-induced antitumor activity was observed when the known calmodulin inhibitor trifluoperazine (TFP) was coincubated with IFN-gamma. At concentrations of 4-10 microM, the antitumor activity of IFN-gamma was increased nearly 400%. These observations suggest that the pattern of halothane potentiation of the antitumor activity of IFN-gamma is similar to that exhibited by known calmodulin inhibitors. PMID- 1898841 TI - Respiratory effects of clonidine alone and combined with morphine, in humans. AB - Because only limited and controversial data exist concerning the respiratory effects of clonidine in humans, the authors evaluated the respiratory effects of clonidine alone and in combination with morphine, in 12 healthy adult males. Subjects received clonidine (0.3-0.4 mg orally), morphine (0.21 mg/kg intramuscularly), or the same doses of the two drugs combined, at three separate sessions in a randomized fashion. The study was balanced for all possible sequences of drug administration. Blood pressure, heart rate, hemoglobin oxygen saturation via finger pulse oximetry, and ventilatory and occlusion pressure responses to CO2 were obtained before and 20, 40, 60, 90, 120, 180, 240, 300, and 360 min after administration of drug or drug combination. Systolic blood pressure decreased significantly only in the clonidine and clonidine plus morphine groups (P less than 0.05). Hemoglobin oxygen saturation decreased by a statistically significant (P less than 0.05), though clinically minor, degree only in the morphine or morphine plus clonidine groups. Clonidine alone did not depress the slope of either the ventilatory or the occlusion pressure response to CO2. In addition, clonidine did not significantly worsen morphine-induced depression of the slope of the ventilatory and occlusion pressure responses in the drug combination group. Both the ventilatory and occlusion pressure responses to CO2 were shifted to the right in all three drug groups (P less than 0.05) but were shifted to a significantly lesser degree by clonidine alone than by morphine and morphine plus clonidine. In healthy young adult males, clonidine alone produces little respiratory depression and does not significantly potentiate morphine induced respiratory depression. PMID- 1898842 TI - The ventilatory response to endogenous CO2 in preterm infants. AB - The measurement of the ventilatory response to inhaled CO2 is unphysiologic because the CO2 that normally stimulates breathing is endogenous (tissue or venous CO2). We took advantage of the spontaneous changes in alveolar PCO2 and ventilation occurring in preterm infants during periodic breathing to calculate the ventilatory response to endogenous CO2. This response was obtained in 20 infants and compared with those obtained using the more conventional methods of steady-state inhalation of CO2 (12 infants) and rebreathing of CO2 (11 infants); it was also compared with a transient change in alveolar CO2 obtained by inhalation of 7% CO2 in air for 10 s (CO2 "bolus"; 11 infants). All groups of infants had similar birth weight and gestational ages. To calculate the response to endogenous CO2, delta PACO2 was measured as the difference between lowest and highest PaCO2 and delta VE was the difference between the corresponding instantaneous ventilation. To adjust for circulation time, values for PACO2 were made lowest for the last breath before apnea and highest for the first breath after apnea. The coefficient of variation of the method was 8%. The slope of the ventilatory response to endogenous CO2 was 0.067 +/- 0.009 (mean +/- SE) L.min 1.kg-1.mm Hg PACO2(-1), a value greater than that using steady-state and rebreathing methods (0.038 +/- 0.004 and 0.040 +/- 0.006 L.min-1.kg-1.mm Hg PACO2(-1), respectively), but similar to that of infants inhaling a CO2 "bolus" (0.051 +/- 0.009 L.min-1.kg-1.mm Hg PACO2(-1)).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1898843 TI - Pathogenesis of pulmonary fibrosis in interstitial lung disease. Alveolar macrophage PDGF(B) gene activation and up-regulation by interferon gamma. AB - Alveolar macrophages are believed to be central in orchestrating the fibrotic response in interstitial lung disease (ILD). To test the hypothesis that macrophages from patients with ILD were dedicated to growth factor production and that this was independent of other indices of macrophage activation, we measured the mRNA of the B chain of PDGF and TGF-beta, as well as HLA-DR-alpha in alveolar macrophages from patients with ILD and from normal control subjects. When alveolar macrophages were examined immediately after lavage, cells from patients with ILD had increased PDGF(B) but similar TGF-beta and HLA-DR-alpha mRNA when compared with control subjects. Discoordinate regulation of these genes was observed when alveolar macrophage PDGF(B) mRNA increased while TGF-beta and HLA DR-alpha mRNA decreased after culture for 24 h. This response was not disease related as these changes were similar in cells from patients with ILD and from control subjects. Because a lymphocytic alveolitis is present in many cases of ILD, we asked whether interferon gamma (IFN-gamma) modulated the activation of these genes. In both the patients and the control subjects, PDGF(B) and HLA-DR alpha, but not TGF-beta, mRNA were increased after incubation with IFN-gamma. These results indicate that PDGF(B) mRNA may be increased in alveolar macrophages in ILD and that PDGF(B), TGF-beta, and HLA-DR-alpha are independently regulated genes in alveolar macrophages, but that IFN-gamma increases both PDGF(B) and HLA DR-alpha mRNA. We speculate that IFN-gamma induced PDGF(B) gene activation may be an important mechanism by which lymphocytes promote pulmonary fibrosis. PMID- 1898844 TI - Arachidonic acid metabolism. Implications of biological chemistry for lung function and disease. PMID- 1898845 TI - Interpretation of the alveolar-arterial oxygen difference in patients with hypercapnia. AB - According to conventional wisdom the difference between alveolar and arterial O2 tensions, the AaPO2, should distinguish between hypoxemia caused by alveolar hypoventilation and hypoxemia caused by alveolar hypoventilation complicated by other abnormalities of gas exchange. To test this concept we have calculated the AaPO2 from arterial blood gas measurements, breathing air, in 23 patients with hypercapnia, hypoxemia, and advanced obstructive lung disease (mean FEV1 = 0.88 L). We found that AaPO2 varied inversely with PaCO2 (r = -0.83, p less than 0.001). In five of these patients with the most severely elevated PaCO2 (range, 59 to 81 mm Hg) the AaPO2 was within normal limits. We also calculated the difference between the O2 contents of "ideal" pulmonary capillary blood and arterial blood and expressed this as the venous admixture (QVA/QT) based on an assumed arteriovenous content difference of 4.5 ml/dl. In contrast to the AaPO2, the QVA/QT, was abnormal in all patients (mean = 41 +/- 8%). We conclude that the AaPO2 may be an unreliable indicator of abnormal gas exchange in the presence of alveolar hypoventilation. This finding can be explained by substantial changes in the position of the alveolar and arterial points on the oxygen dissociation curve for hemoglobin in the presence of alveolar hypoxia secondary to hypoventilation. PMID- 1898846 TI - Increased levels of serum interferon-gamma in pulmonary sarcoidosis and relationship with response to corticosteroid therapy. AB - The aim of this study was to evaluate serum levels of the lymphokine interferon gamma (IFNg) in patients with chronic pulmonary sarcoidosis, and to investigate its value as a predictive marker of clinical response to corticosteroid therapy. Twenty-five patients and 28 age-matched control subjects were studied. All the patients had parenchymal shadows (Stage II or Stage III) and none had clinical evidence of extrathoracic disease. Before therapy, serum IFNg levels were significantly higher in the patient group (p less than 0.001), and 20 (80%) had values above the normal range. After oral treatment with corticosteroids for a median 13 months (range, 3 to 49 months) the levels decreased significantly (p less than 0.01). However, the falls were less pronounced in patients who had a better outcome in terms of achieving complete radiographic resolution and in those who improved in forced vital capacity by greater than or equal to 10%. The prognostic value of the pretreatment serum IFNg was explored, and a significant relationship was found between higher pretreatment levels and lower grades or radiographic abnormality assessed 3 yr after commencement of treatment (p less than 0.01). In addition, the patients who had cleared completely while receiving steroids and remained in remission had significantly higher pretreatment serum IFNg levels than did those with incomplete resolution of parenchymal shadows or radiographic relapses (p less than 0.05). We conclude that elevated levels of circulating IFNg are detectable in most untreated patients with Stage II/III pulmonary sarcoidosis and that patients with the highest levels appear to have a better chance of achieving complete resolution with corticosteroid therapy. PMID- 1898847 TI - Impact of human immunodeficiency virus type 1 on tuberculosis in rural Haiti. AB - We conducted a case-control study to determine the relative and attributable risk of HIV seropositivity for bacillary-positive (smear and/or culture) pulmonary tuberculosis in Haiti. There were 274 patients with tuberculosis and an equal number of control subjects. Antibodies to HIV were present in 67 (24%) patients and eight (3%) control subjects. Odds ratios suggested that the risk of pulmonary tuberculosis was 15.7 times as great (95% confidence interval, 4.8 to 5.0; p less than 0.05) in patients 20 to 39 yr of age who were HIV-seropositive than in HIV seronegative patients. In contrast, the relative risk in those 40 to 59 yr of age was elevated (3.0 times), though not significantly (lower 95% confidence interval, 0.8). In the 20- to 39-yr age group, 31% of tuberculosis was attributable to HIV infection (95% confidence interval between 23 and 39%). HIV seropositive and HIV-seronegative patients did not differ with respect to sputum smear positivity. HIV-seronegative patients were twice as likely to be infected with resistant organisms, though this was not significant. We conclude that HIV infection is a major risk factor for pulmonary tuberculosis in young adult residents of Haiti. This, together with the fact that similar proportions of HIV seropositive and HIV-seronegative patients were potentially infectious, suggests that without vigorous counteraction tuberculosis will become a greater problem for Haiti. PMID- 1898848 TI - Early combination of selegiline and low-dose levodopa as initial symptomatic therapy in Parkinson's disease. Experience in 26 patients receiving combined therapy for 26 months. AB - Thirty-eight patients newly diagnosed as having Parkinson's disease (mean age, 57.3 years; mean Parkinson's disease duration, 2.7 years) in the earlier phase of the disease (mean Hoehn/Yahr stage, 2; mean motor scores, 11.4) were given selegiline (Deprenyl), 10 mg daily, and maintained on this drug alone until significant clinical worsening warranted the addition of low-dose levodopa (Sinemet, 25/100 three to four doses per day). Five of these patients were not yet receiving additional levodopa despite some worsening of motor scores. Of the 33 patients now taking combined therapy, seven have been followed up for 6 months or less. Twenty-four (92%) of the 26 patients taking combined therapy for a mean of 26 months (8.5 to 99 months) who have had Parkinson's disease for 6 years showed a dramatic improvement in their parkinsonism shortly after the addition of levodopa, with significant decreases in their rated motor scores, such improvement being maintained at their latest neurologic evaluation. Eighteen (75%) of these 24 patients responded to the combined selegiline/levodopa therapy with degrees of improvement equal to or greater than 50%, compared with their motor status at the start of combined therapy just before the addition of levodopa. This degree of "reversal" of parkinsonism on addition of levodopa (mean carbidopa/levodopa dose, 98/389 mg) was not observed in any of these same patients receiving selegiline alone for an average of 13.8 months. Four patients taking combined therapy developed mild, transient, abnormal involuntary movements, and end-of-dose pattern of response after more than 2 years of combined therapy (24.75 and 33.5 months, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1898849 TI - Effects of the anti-AIDS drug dideoxyinosine on hepatic glycolysis in the perfused rat liver: role of intracellular calcium stores. PMID- 1898850 TI - The influence of retinal innervation on neurogenesis in the first optic ganglion of Drosophila. AB - We have examined the influence of retinal innervation on the development of target neurons in the first optic ganglion, the lamina, of D. melanogaster. Mitotically active lamina precursor cells (LPCs), which normally produce lamina neurons, are absent in mutants that lack retinal innervation, while other proliferative centers appear unaffected. Reducing the number of innervating photoreceptor axons results in fewer mitotic LPCs. In glass mutants photoreceptors project to abnormal locations and LPCs are found adjacent to these aberrant projections. We conclude that the arrival of photoreceptor axons in the larval brain initiates, directly or indirectly, cell division to produce lamina neurons. Our results provide an explanation for how the synchronous development of these two interacting systems is coordinated. PMID- 1898851 TI - Oxidant-induced cytotoxicity: a challenge for metabolic modulation. PMID- 1898852 TI - Effects of human neutrophil elastase and Pseudomonas aeruginosa proteinases on human respiratory epithelium. AB - It has been suggested that proteinase enzymes could play an important role in the pathogenesis of chronic bronchial infections including bronchiectasis and cystic fibrosis (CF). Because Pseudomonas aeruginosa frequently colonizes the respiratory tract in bronchiectasis and CF, we examined the in vitro effects of human neutrophil elastase (HNE) and proteinase enzymes produced by P. aeruginosa (elastase: PE; alkaline proteinase: PAP) on the ciliary beat frequency (CBF) and ultrastructure of human nasal ciliated respiratory epithelium. HNE (500 micrograms/ml) progressively reduced CBF and caused marked epithelial disruption; lower concentrations (100 and 20 micrograms/ml) also caused epithelial disruption but without slowing CBF. The effects of HNE (500 micrograms/ml) were completely abolished by adding alpha 1-antitrypsin (5 mg/ml). There was no synergy between HNE and pyocyanin, a product of P. aeruginosa which slows CBF. PE in phosphate buffered saline also caused epithelial disruption without slowing CBF; however, PE in medium containing divalent metal ions caused CBF slowing as well as epithelial disruption at 100 micrograms/ml. PAP (500 micrograms/ml) had almost no effect on ciliated epithelium. The effects of HNE and PE on nasal and bronchial epithelium obtained from the same patient were similar. Light and transmission electron microscopy revealed that HNE and PE were cytotoxic and caused detachment of epithelial cells from neighboring cells and the basement membrane. There was cytoplasmic blebbing of the cell surface and mitochondrial damage; however, no increase of abnormalities in the ultrastructure of cilia on living cells was seen. These results support the hypothesis that HNE and PE contribute to the delayed mucociliary clearance and epithelial damage that is observed in patients with chronic bronchial infection. PMID- 1898853 TI - Doctors and nurses. Facts and fantasies. PMID- 1898854 TI - Mental handicap nursing. Change of scene. PMID- 1898855 TI - Playing safe on funding. PMID- 1898856 TI - Meeting the challenge of a new Europe. AB - Tony Butterworth gives an overview of the collaborative work which awaits nursing as Europe removes its boundaries and becomes a federation of associated interests. He also addresses the work of the World Health Organization, the International Council of Nurses, the European Community, and finally research being conducted by the University of Manchester which is examining those subjects which most interest nurses in Europe. PMID- 1898857 TI - Self-administration of medicines. AB - In the fourth of this six-part series on nurse prescribing, Susan Davis assesses the advantages and disadvantages of patient self-administration of medicines in hospital. The former, she asserts, considerably outweigh the latter; a controlled self-administration programme can hasten a patient's progress towards full independence and ease the often difficult transition period following discharge. The problems experienced by specific groups of patients such as those with visual or manual dexterity deficits are considered and guidelines for practice offered. PMID- 1898858 TI - Serving whom? PMID- 1898859 TI - Planning quality: one region's approach. AB - Rosemary Webster describes an initiative taken in Mersey Region to ensure all nurses understand the importance of standard setting. The initiative, prompted by a number of factors, saw the establishment of a steering group whose Statement of Purpose outlined a framework for standard setting in each district. As a result, nurses are now playing a leading role in this increasingly important aspect of health care. PMID- 1898860 TI - Student nurses and counselling services. AB - Studies have shown that health service staff are often reluctant to talk about their own problems and tend to be cautious about admitting to ill health. Margaret Doust describes a study involving student nurses and their perceptions of an existing counselling service. The results show that while the vast majority of students were positive in their attitude to the service, many said they would feel embarrassment or anxiety at the idea of visiting a counsellor to discuss a problem. PMID- 1898861 TI - Communicating with patients in ICU. AB - Intensive care is an area which promotes feelings of high anxiety among patients, relatives and nurses. In such a highly-charged atmosphere, it is easy for communication problems to occur. Chris Turnock explores the reasons for poor nurse-patient communication in intensive care, and suggests that this might be largely due to the insecurities felt by nurses. While there are a number of factors which influence communication, emphasis should be placed on the quality of the nurse-patient interaction. PMID- 1898862 TI - Insomnia--nursing's curse. PMID- 1898863 TI - Management. Speaking out on violence. PMID- 1898864 TI - Private lies and deception. PMID- 1898865 TI - Looking for a winner. PMID- 1898866 TI - Noncovalent complex between domain AB and domains CD*EF of parvalbumin. AB - The interaction between domain AB and domains CD*EF of pike parvalbumin III has been studied by intrinsic fluorescence spectroscopy. In the presence of Ca2+ ions, parvalbumin fragment 38-108 containing two calcium binding sites interacts with the short peptide 1-37 with association constant 10(5.3 +/- 0.5) M-1. Removal of Ca2+ ions results in the disappearance of the interaction. The affinity of the complex of the two fragments for calcium is 50-times higher than the affinity of the isolated fragment 38-108, but slightly lower than that of the intact protein. PMID- 1898867 TI - Lithium therapy for fibromyalgia. PMID- 1898868 TI - Ionic versus nonionic contrast media: a burden or a bargain? PMID- 1898869 TI - The ethics of forced feeding in anorexia nervosa. PMID- 1898870 TI - Indirect costs of teaching in Canadian hospitals. AB - We sought to determine whether there are indirect costs of teaching in Canadian hospitals. To examine cost differences between teaching and nonteaching hospitals we estimated two cost functions: cost per case and cost per patient-day (dependent variables). The independent variables were number of beds, occupancy rate, teaching ratio (number of residents and interns per 100 beds), province, urbanicity (the population density of the county in which the hospital was situated) and wage index. Within each hospital we categorized a random sample of patient discharges according to case mix and severity of illness using age and standard diagnosis and procedure codes. Teaching ratio and case severity were each highly correlated positively with the dependent variables. The other variables that led to higher costs in teaching hospitals were wage rates and number of beds. Our regression model could serve as the basis of a reimbursement system, adjusted for severity and teaching status, particularly in provinces moving toward introducing case-weighting mechanisms into their payment model. Even if teaching hospitals were paid more than nonteaching hospitals because of the difference in the severity of illness there should be an additional allowance to cover the indirect costs of teaching. PMID- 1898871 TI - Periplasmic interaction between two membrane regulatory proteins, ToxR and ToxS, results in signal transduction and transcriptional activation. AB - ToxR is a transmembrane, DNA-binding protein that can activate transcription of genes encoding cholera toxin (ctxAB). Here we characterize ToxS, a 19 kd transmembrane regulatory protein that interacts with ToxR and stimulates its activity. If a portion of the periplasmic domain of ToxR is deleted, productive interaction with ToxS is abolished. A ToxR-PhoA fusion protein that retains most of the ToxR periplasmic region remains dependent on ToxS for its ToxR activity. ToxS protects this fusion from proteolytic cleavage, suggesting that these two proteins interact within the periplasm. Mutations in a short cytoplasmic domain of ToxR were isolated that disrupt the periplasmic interaction between ToxR and ToxS. This domain is shared by other bacterial transcriptional activators, suggesting that it may play a common role in function of these proteins and in the molecular mechanism of signal transduction. PMID- 1898872 TI - Self-splicing introns in prokaryotes: migrant fossils? PMID- 1898873 TI - Thymic selection in CD8 transgenic mice supports an instructive model for commitment to a CD4 or CD8 lineage. AB - Immature thymocytes, which coexpress CD4 and CD8, give rise to mature CD4+CD8- and CD4-CD8+ T cells. Only those T cells that recognize self-MHC are selected to mature, a process known as positive selection. The specificity of the T cell antigen receptor (TCR) for class I or class II MHC influences the commitment to a CD4 or CD8 lineage. This may occur by a directed mechanism or by stochastic commitment followed by a selection step that allows only CD8+, class I-specific and CD4+, class II-specific cells to survive. We have generated a mouse line expressing a CD8 transgene under the control of the T cell-specific CD2 regulatory sequences. Although constitutive CD8 expression does not affect thymic selection of CD4+ cells, selection of a class I-specific TCR in the CD8 subset is substantially improved. This outcome is consistent with a model for positive selection in which selection occurs at a developmental stage in which both CD4 and CD8 are expressed, and positive selection by class I MHC generates an instructive signal that directs differentiation to a CD8 lineage. PMID- 1898874 TI - Lack of correlation between end-tidal carbon dioxide concentrations and Paco2 in cardiac arrest. PMID- 1898875 TI - Validation of the Glasgow Meningococcal Septicemia Prognostic Score: a 10-year retrospective survey. AB - OBJECTIVE: To derive performance characteristics for the Glasgow Meningococcal Septicemia Prognostic Score (GMSPS). DESIGN: Retrospective case-note study. SETTING: Two children's hospitals with Regional Intensive Care Unit. PATIENTS: One hundred twenty-three children with proven meningococcal septicemia (some with concurrent meningitis) from January 1, 1977 to December 31, 1986. MEASUREMENTS AND MAIN RESULTS: All 14 children who died after arrival scored greater than or equal to 8 either on admission (n = 8) or afterward (n = 6). Of 109 survivors, five scored greater than or equal to 8 (two were postictal at the time of scoring). A GMSPS of greater than or equal to 10 at or after admission predicted death with sensitivity 100%, specificity 98%, and positive predictive value of 88%; for GMSPS of both greater than or equal to 8 or 9, the values were 100%, 95%, and 74%, respectively. CONCLUSIONS: The GMSPS is a rapid clinical score that performs well in identifying children with poor prognosis who might benefit from early intensive care. It should be studied prospectively and compared with other scoring systems. PMID- 1898876 TI - Total parenteral nutrition increases mortality after hemorrhage. AB - OBJECTIVES: To determine the effect of total parenteral nutrition (TPN) and different enteral feeding formulas on survival and liver function following hemorrhage in rats. DESIGN: Prospective randomized controlled study. SETTING: Laboratory of a large university-affiliated medical school. SUBJECTS: Sixty-seven male Sprague-Dawley rats weighing 350 to 450 g. INTERVENTIONS: Jugular and gastroduodenal feeding catheters were inserted in animals 1 day before hemorrhage, and animals were started on one of six different fluid or nutritional regimens: TPN, iv saline, an enteral amino acid-based formula (AA) (Vivonex-TEN), an enteral peptide-based formula (PEP) (Reabilan-HN), an enteral intact-protein based formula (PRO) (Osmolite-HN), or enteral saline. A catheter was inserted in the tail artery and animals were hemorrhaged 5 mL/kg at baseline and 1 hr later. Animals were returned to their cages and observed for survival. Liver function was determined by measuring circulating bile acid levels at baseline and 24 hr after hemorrhage. MEASUREMENTS AND MAIN RESULTS: Mortality was significantly increased in animals receiving TPN (63%) and AA (24%). Mortality was 13% in animals receiving PRO and 0% in animals receiving PEP and saline. Liver function deteriorated in all animals after hemorrhage except the PEP group. CONCLUSIONS: TPN and AA increased mortality in animals after hemorrhage. PEP was associated with zero mortality and protection of liver function after hemorrhage. PMID- 1898877 TI - Total parenteral nutrition versus total enteral nutrition or resuscitation versus nutrition? PMID- 1898878 TI - [The psychological aspects of diabetics with the secondary failure of sulfonylurea therapy]. AB - Forty diabetics (19 men, 21 women; mean age 54 [41-66] years) with secondary failure of sulfonylurea treatment, were assessed by questionnaire (psychological neurological state; scale of well-being; attitude towards achievement, and psychological aspects of performance), both before and four months after being put on insulin treatment, as to the way in which they experienced and dealt with the illness. Before the onset of insulin treatment, a general decrease in performance was the predominant symptom (29 patients), while only about half of the patients declared diabetes-specific symptoms. The necessity of insulin administration was experienced by 34 patients as a severe crisis in their chronic illness. Anxiety over failure in the act of injection (30 patients), as well as fear of the consequences regarding their job (25 patients) and of restriction in the personal sphere (31 patients) were the chief reasons for their dislike of insulin treatment. Four months after starting insulin treatment these anxieties had largely disappeared. The only remaining fear was that the necessity of insulin treatment meant that a serious stage of the disease had been reached (before insulin, 36; after insulin 18 patients). It is concluded that such patients should, as part of group therapy, become active participants in the instructions given to diabetics so that other patients can profit from their experience. PMID- 1898879 TI - A new role for follicle-stimulating hormone in the regulation of calcium flux in Sertoli cells: inhibition of Na+/Ca++ exchange. AB - Elucidation of mechanisms regulating intracellular calcium levels in steroidogenic tissues is important for understanding control of cellular function. We have previously described FSH receptor-mediated flux of 45Ca++ into cultured rat Sertoli cells and receptor-enriched proteoliposomes via voltage sensitive and voltage-independent calcium channels. In the present study, we report heretofore unrecognized inhibitory effects of FSH on Na+/Ca++ exchange in these two systems. An outwardly directed Na+ gradient, developed by preincubating Sertoli cell monolayers in buffer made hypertonic with NaCl, resulted in uptake of 45Ca++ that was unaffected by calcium channel blocking agents, ruthenium red or methoxyverapamil, but was enhanced by ouabain, a specific inhibitor of Na+/K(+)-ATPase. Sodium-dependent 45Ca++ flux into Sertoli cells was inhibited in a concentration-related manner by increased extracellular Na+ (up to 135 mM). FSH consistently and reproducibly (28.9 +/- 3.8%, 10 separate assays) reduced sodium dependent 45Ca++ influx in the absence or presence of ouabain. A lesser effect on Na+/Ca++ exchange was seen when Li+ replaced Na+ in the preincubation buffer, and a marked reduction occurred when Sertoli cells were incubated in buffer containing KCl, presumably due to membrane depolarization. FSH-sensitive Na+/45Ca++ exchange was also observed when using FSH receptor-enriched proteoliposomes. Our earlier calcium channel studies indicated that FSH affects Ca++ entry into Sertoli cells via a receptor-mediated process. The results reported here demonstrate that the interaction of FSH with its receptor is associated with changes in Na+/Ca++ exchange as well, and suggest that this activity may also be involved in regulating intracellular free Ca++ levels in the Sertoli cell. PMID- 1898880 TI - Follicle-stimulating hormone and insulin regulation of 17 beta-estradiol secretion and granulosa cell proliferation within immature rat ovaries maintained in perifusion culture. AB - The present study examined the effects of FSH and insulin (IN) on 17 beta estradiol (E2) secretion and granulosa cell proliferation. For these studies, immature rat ovaries were maintained in perifusion culture and continuously exposed to FSH (0-800 ng RP-1 eq/ml) and /or IN (0.2 U/ml). At specific times, the ovaries were removed from perifusion, and the perifusate was assayed for E2 by RIA. The ovaries were then incubated with [3H]thymidine ([3H]T) in order to estimate granulosa cel mitotic activity. FSH increased E2 secretion in a dose dependent manner (P less than 0.05), but did not enhance [3H]T incorporation (P greater than 0.05) after 48 h of perifusion. Conversely, IN increased [3H]T incorporation (P less than 0.05) without stimulating E2 secretion (P greater than 0.05) after 48 h of perifusion. FSH alone or in combination with IN stimulated [3H]T incorporation at 24 h of perifusion compared to both zero hour control (P less than 0.05) and IN treatments (P less than 0.05). The inability of FSH to stimulate [3H]T incorporation after 48 h did not appear to be due to increased E2, since IN stimulated [3H]T incorporation in the presence of 100 ng E2/ml. Further, continuous exposure to FSH was required to maintain E2 secretion, demonstrating that after 24 h, FSH loses its capacity to stimulate granulosa cell [3H]T incorporation, but not E2 secretion. Finally, when ovaries are pretreated with FSH for 48 h and then exposed to FSH and/or IN, [3H]T incorporation was stimulated, and E2 secretion inhibited. These data suggest that 1) initially, FSH acts to stimulate mitosis then promotes granulosa cell E2 secretion; and 2) once granulosa cells begin to secrete E2 they are still capable of mitosis, but their mitotic activity is no longer directed by FSH. PMID- 1898881 TI - Acute inhibitory effects of 17 beta-estradiol are observed on gonadotropin secretion from perifused pituitary fragments of metestrous, but not proestrous, rats. AB - The in vivo suppression of LH by 17 beta-estradiol (E2) has been documented frequently. However, the demonstration of a direct inhibitory action of E2, in contrast to a stimulatory action, on the secretion of LH from the anterior pituitary has been inconsistent. The aim of this study was to determine if E2 can suppress either basal (unstimulated) or GnRH-stimulated gonadotropin secretion directly at the level of the anterior pituitary gland. Anterior pituitaries were obtained from metestrous and proestrous females rats at 0900 h, and trunk blood was collected for serum measurements of LH, FSH, E2, and progesterone (P). Each anterior pituitary was cut into eighths and placed into a microchamber for perifusion. Pituitary fragments were perifused at a rate of 10 ml/h using medium 199 (without phenol red) that contained E2 (1 nM) or ethanol as a control. Six pulses of GnRH (peak amplitude, 50 ng/ml; duration, 2 min) were administered one per h starting at 60 min. Fractions of perfusate were collected every 5 min for measurement of LH and FSH. The total amounts of LH and FSH secreted during the 1 h interval after each GnRH pulse or corresponding basal hour were calculated. Both basal and LH and FSH responses to GnRH were significantly greater from pituitaries of proestrous compared to metestrous rats. The selective suppression of LH secretion by in vitro treatment with E2 was demonstrated using pituitaries from metestrous rats receiving GnRH pulses, but not using pituitaries from proestrous rats. Thus, a negative feedback effect of E2 on LH secretion was observed only in pituitaries from donors with low serum levels of E2 and high P, but not from donors with high serum levels of E2 and low P. We believe that the in vivo steroid environment determined the subsequent responses to in vitro treatment with E2 on GnRH-stimulated gonadotropin secretion from the isolated pituitary gland. PMID- 1898883 TI - Evidence that secretion of immunoactive inhibin by seminiferous tubules from the adult rat testis is regulated by specific germ cell types: correlation between in vivo and in vitro studies. AB - This study has assessed whether depletion of specific germ cell types is able to alter the secretion of immunoactive inhibin by adult Sertoli cells in vivo and in vitro. Pachytene and later spermatocytes were depleted (80-100%) by a single administration of methoxy acetic acid (MAA; 650 mg/kg) to adult rats. At intervals between 1 and 42 days posttreatment, rats were killed, and the blood levels of FSH, LH, and testosterone were determined together with the levels of immunoactive inhibin in plasma and testicular interstitial fluid (IF). At the same time intervals, seminiferous tubules (ST; 5 x 2 cm) were isolated from control and MAA-treated rats and cultured for 24-72 h in the presence or absence of rat FSH, (Bu)2cAMP, or MAA under rigorously optimized conditions. The hormonal changes observed were related to the presence/absence of specific germ cell types, as determined by assessment of testicular morphology in perfusion-fixed testes from similarly treated rats. One to 3 days after MAA treatment, coincident with the depletion of pachytene spermatocytes, blood levels of FSH were increased significantly compared with controls; FSH returned to control levels at 7-14 days (when early spermatids were depleted), but were increased again at 21-35 days (when late spermatids were depleted). In contrast, while the plasma levels of immunoactive inhibin were increased 2-fold 3 days posttreatment, they were comparable to controls at 7-14 days, but were decreased substantially at 21-28 days. The levels of immunoactive inhibin in testicular IF were more than doubled 1 and 3 days posttreatment, but were comparable to control levels at all other times. Blood levels of LH showed a similar pattern of change to FSH, although only at 21-28 days after MAA treatment was there a significant increase, while blood levels of testosterone were comparable at all times in control and MAA treated rats. To confirm that the changes observed in vivo after MAA treatment were indicative of changes in Sertoli rather than Leydig cell secretion of immonoactive inhibin, its secretion by isolated ST was assessed, and a pattern of change similar to that in plasma was observed. Thus, when cultured for 24 h under basal conditions, ST from rats 1-3 days after MAA treatment showed a 2- to 3-fold increase in secretion of immunoactive inhibin, which returned to control levels at 7-14 days before being reduced substantially at 21-28 days and then recovering to control levels; similar changes were observed for FSH- and (Bu)2cAMP stimulated secretion of immunoactive inhibin.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1898882 TI - Differential roles of high and low affinity guanosine 5'-triphosphate binding sites in the regulation of follicle-stimulating hormone binding to receptor and signal transduction in bovine calf testis membranes. AB - We have previously shown that FSH receptors are physically and functionally associated with a guanine nucleotide regulatory protein (Gs) in membranes of calf testis. Using N-ethylmaleimide (NEM), forskolin, and cholera toxin as probes, we have investigated the role of low and high affinity GTP-binding sites of stimulatory guanine nucleotide-binding protein of adenylate cyclase (Gs) in the activation of adenylate cyclase. When calf testis membranes were exposed to NEM (1 mM), FSH binding to receptors was slightly (30%) decreased, but the receptors showed continued sensitivity to GTP, resulting in a further decrease in [125I]human FSH binding to receptors. Pretreatment of membranes with NEM (up to 20 microM) produced no effect on GTP-binding. A dose-dependent decrease in high affinity GTP-binding sites, however, was observed at higher (greater than 50 microM) NEM. Adenylate cyclase activity was reduced in response to GTP gamma S or NaF concomitant to a decrease in high affinity GTP-binding sites in membranes treated with 50-100 microM NEM, or completely abolished in membranes exposed to 300 microM NEM. Stimulation by forskolin indicated that the significant inhibition of adenylate cyclase activity occurring in membranes exposed to low NEM (50-100 microM) was not due to inactivation of catalytic unit of adenylate cyclase by NEM. Pretreatment of membranes with 100 micrograms/ml cholera toxin and NAD slightly (18%) reduced specific FSH binding but did not affect Gpp(NH)p binding. However, adenylate cyclase stimulation by GTP plus FSH in these membranes was significantly enhanced. When membranes were treated with higher concentration of cholera toxin (250 micrograms/ml), the adenylate cyclase stimulation by GTP plus FSH was abolished due to uncoupling of FSH receptors from Gs and a significant decrease in high affinity GTP-binding sites. Our results suggest that high affinity GTP-binding sites of Gs coupled to FSH receptors are essential for FSH and guanine nucleotide activation of adenylate cyclase. The low affinity binding sites bind GTP and thereby regulate FSH binding but are not involved in the activation of adenylate cyclase. PMID- 1898884 TI - Pituitary and gonadal hormone-dependent and -independent induction of follicle stimulating hormone receptors in the developing testis. AB - The number of FSH receptors increases during testicular development in several species of mammals. Hypophysectomy and hormonal replacement were performed to identify the factors that induce developmental changes in testicular FSH receptors. Male rats of the Wistar/Tw strain were hypophysectomized at 9, 16, 23, or 30 days or 3 months of age. These rats were killed 10 days after surgery along with intact control rats, and the testes were removed for receptor assay. A group of intact rats was killed on the day of surgery as initial controls. All of the hypophysectomized immature rats showed a higher density of FSH binding (FSH binding per unit weight) and a lower total FSH binding (FSH binding per two testes) compared with each of the matched intact control rats. In contrast to FSH binding, not only the total LH binding but also the density of LH binding were invariably lower in the hypophysectomized rats than in the intact control rats. Unlike hypophysectomy at other immature ages, surgery at 9 days of age was followed by significant increases in testicular weight, density of FSH binding, and total FSH binding compared with those values in the initial control rats. There was no significant effect of hypophysectomy on total FSH binding in adult animals, in contrast to the marked decrease in total LH binding. When male rats hypophysectomized at 25 days of age were injected with FSH for 5 days beginning on the 11th day after surgery, dose-dependent increases in total FSH binding and testicular weight were observed. Testosterone treatment induced an increase only in the total FSH binding, but its effect was less potent. Scatchard plot analyses of the binding suggested that changes in FSH binding with age, after hypophysectomy, and after hormonal administration were due to changes in the number of binding sites. Plasma FSH concentrations in all postoperative rats were below or at the level of detectability, indicating that hypophysectomy was successful. In normal immature rats, a significant increase in the plasma FSH level was detected only from 9-19 days of age, in contrast to the continuous increase in total FSH binding during testicular development. These results suggest that FSH and testosterone act as hormonal factors to induce an increase in the number of FSH receptors in the developing testis. Other factors that are independent of pituitary and sex hormones may also contribute to FSH receptor induction. PMID- 1898885 TI - Early miscarriage and fetal malformations after induction of ovulation (by clomiphene citrate and/or human menotropins), in vitro fertilization, and gamete intrafallopian transfer. AB - From the reviewed data, it appears that CC, hMG-hCG, or the association of these drugs with IVF-ET and GIFT programs do not carry an increased risk for congenital malformations as a whole, nor is there any specific malformation that has an increased incidence or is related in any way with the use of these drugs. Table 7 represents the specific malformation rate per 1,000 births in the general population and in newborns delivered after treatment with CC, hMG-hCG, or IVF-ET and GIFT. The malformation rate in the treated groups does not differ from that of the general population. However, as shown by McIntosh et al., the incidence of congenital malformations often rises with a longer follow-up. Most of the reports about babies born after ovulation induction are based on the initial examination done shortly after birth. Thus, studies including examination of these infants up to at least 12 months of age will be undoubtedly of value. Also, data concerning the reproductive capability of women born after ovulation induction is lacking. With regard to the abortion rate in pregnancies achieved after such treatments and procedures, it can be concluded that it does not appear to be higher than that of the general population, particularly when early pregnancy loss, advanced maternal age, the infertility status, and the increased incidence of multiple pregnancies occurring in these patients are taken into consideration. PMID- 1898886 TI - Alterations in luteal phase progesterone and estradiol production after leuprolide acetate therapy before ovarian stimulation for in vitro fertilization. AB - The impact of pituitary suppression with a gonadotropin-releasing hormone agonist (GnRH-a) on the luteal phase of in vitro fertilization (IVF) cycles was examined in 21 women who underwent identical stimulation regimens with and without leuprolide acetate pretreatment. The areas under the serum progesterone curves, measured over the 1st 10 days of the luteal phase, were significantly greater in the GnRH-a cycles compared with the non-GnRHa cycles, but when calculated per oocyte retrieved were similar in GnRH-a and non-GnRH-a cycles. In contrast, the areas under the luteal phase serum estradiol curves were significantly less in the GnRH-a cycles. These data suggest that GnRH-a treatment is accompanied by potentially beneficial alterations in the systemic steroidal milieu of the luteal phase of IVF cycles. PMID- 1898887 TI - Decrease in luteal gonadotropin concentration in conception cycles after in vitro fertilization/gamete intrafallopian transfer. AB - The concentrations of the gonadotropins, luteinizing hormone (LH), and follicle stimulating hormone (FSH) were measured in the luteal phase of the cycle in patients undergoing ovarian hyperstimulation. In nonconception cycles, FSH and LH were increased in the late luteal phase compared with conception cycles in which both gonadotropins were suppressed. Estradiol (E2) and progesterone concentrations increased in pregnancy cycles and may be the sole cause for the decreased gonadotropin concentrations as shown by equivalent concentrations of LH and FSH in both pregnancy and nonpregnancy cycles after matching for E2 concentrations. Subjects who subsequently had twin pregnancy or a spontaneous abortion were compared with those with a successful ongoing singleton conception. There were no significant differences relative to LH and FSH between the three groups, although in twin pregnancy FSH tended to be lower at day 16 from oocyte recovery. It is concluded that suppression of LH and FSH in hyperstimulated pregnancy cycles occurs after the time of the rising human chorionic gonadotropin concentrations in plasma. PMID- 1898888 TI - Marked suppression of gonadotropins and testosterone by an antagonist analog of gonadotropin-releasing hormone in men. AB - To study the dose response characteristics of a gonadotropin-releasing hormone (GnRH) antagonist ([Ac-D2-Nal1,D4-Cl-Phe2,D3-Pal3,Arg5,dGlu6 (AA), d-Ala10] GnRH; Nal-Glu), 1.5 or 5.0 mg of Nal-Glu were administered to two groups of five normal men by daily subcutaneous injection for 21 days. Serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone (T) were determined on multiple occasions before, during, and after the antagonist treatment. Five milligrams Nal-Glu markedly suppressed mean serum immunoreactive LH to a mean of 1.5 +/- 0.4 IU/L (+/- SEM), immunoreactive FSH to the limit of assay detection (1 IU/L), and lowered basal mean serum T to castrate range (less than 2 nmol/L). Serum bioactive LH levels also showed a marked decrease in the 5.0-mg group similar to that seen in immunoreactive LH levels. Amplitude of immunoreactive LH pulses was markedly reduced in the 5.0-mg group on day 21. A 1.5-mg dose of Nal Glu transiently suppressed serum immunoreactive LH levels on day 1. There was a subsequent escape on the rest of the days sampled. Serum immunoreactive FSH levels were not significantly changed over the 21-day treatment period. Serum T levels were transiently suppressed only on day 1 paralleling immunoreactive LH suppression. No adverse systemic side effects occurred. Thus, the 5.0-mg dose of this GnRH antagonist provides a pharmacological means of markedly suppressing the hypothalamic-pituitary-gonadal axis and, therefore, has potential as a male contraceptive. PMID- 1898889 TI - Gonadotropin-releasing hormone agonists induce meiotic maturation and degeneration of oocytes in the in vitro perfused rabbit ovary. AB - The present study was undertaken to assess the effects of gonadotropin-releasing hormone agonists (GnRH-a, buserelin and leuprolide acetate [LA]) on ovulation, oocyte maturation and degeneration, and steroid and prostaglandin production in the perfused rabbit ovary preparation. Ovulation did not occur in any of ovaries treated with buserelin or LA (10(2) to 10(4) ng/mL) in the absence of gonadotropin. Gonadotropin-releasing hormone agonists were associated with the resumption of meiosis in follicular oocytes in a dose-related manner. Furthermore, the addition of GnRH-a to the perfusate significantly increased the percentage of follicular oocytes that showed evidence of degeneration compared with contralateral untreated or human chorionic gonadotropin-treated controls. Prostaglandin E2 and prostaglandin F2 alpha production by the perfused rabbit ovaries were stimulated significantly by GnRH-a treatment. Exposure to GnRH-a failed to increase either progesterone or estradiol production by the perfused rabbit ovaries. These data demonstrate that GnRH-a act directly in the rabbit ovary to trigger meiotic maturation in oocytes within the follicles, concomitantly increasing oocyte degeneration. PMID- 1898890 TI - The use of biosynthetic human growth hormone to augment ovulation induction with buserelin acetate/human menopausal gonadotropin in women with a poor ovarian response. AB - The present study has demonstrated the usefulness of GH in augmenting buserelin acetate/hMG to stimulate the rate of growth of follicles in women regarded as poor responders. The PR achieved was extremely encouraging in a group of patients whose prognosis was otherwise poor. Further studies are required to confirm these preliminary data. PMID- 1898891 TI - A comparative, randomized study of low-dose human menopausal gonadotropin and follicle-stimulating hormone in women with polycystic ovarian syndrome. AB - Treatment with low-dose follicle-stimulating hormone (FSH) is associated with a high rate of ovulation in anovulatory women with polycystic ovarian syndrome (PCOS), but it is not clear whether the success of treatment is because of the use of pure FSH or the low dose of gonadotropin. We undertook a randomized controlled study to compare the effects of urinary FSH and human menopausal gonadotropin (hMG) using a low-dose regimen in 30 women with PCOS. Each subject received a maximum of three cycles of either FSH or hMG. Ovulation occurred in 75% of subjects and in 77% of cycles induced with FSH and in 94% of women, 85% of cycles of those treated with hMG. A single dominant follicle developed in 70% (FSH) and 65% (hMG) of cycles, respectively. Five singleton pregnancies occurred in each group. This study shows that low-dose FSH and hMG are equally successful in inducing ovulation, suggesting that the success of treatment depends on the low dose of gonadotropin used rather than the presence or absence of luteinizing hormone in the preparation. PMID- 1898892 TI - Use of combined exogenous gonadotropins and pulsatile gonadotropin-releasing hormone in patients with polycystic ovarian disease. AB - We previously tested a combined regimen based on the administration of gonadotropin in the early follicular phase followed by pulsatile gonadotropin releasing hormone (GnRH) until complete follicular maturation in patients suffering from polycystic ovarian disease. Despite good clinical results, a high rate of premature luteinization was observed with this approach. We therefore evaluated in this study whether starting pulsatile GnRH therapy before gonadotropin administration might reduce premature luteinization. Eight women underwent induction of ovulation with both combined therapy and pure exogenous follicle-stimulating hormone alone using a crossover scheme. No premature luteinization and a single follicular growth were recorded with the modified combined regimen. Clinical results (8/8 versus 3/7 ovulatory cycles; 3/8 versus 1/7 pregnancies) favor the combined approach over gonadotropin alone. PMID- 1898893 TI - The role of endogenous gonadotropin release in the etiology of ovarian enlargement during purified urinary follicle-stimulating hormone therapy. AB - Patients with polycystic ovarian disease were grouped into three groups according to their maximum ovarian diameter (maxD) after ovulation induction by purified urinary follicle-stimulating hormone (FSH). Serum luteinizing hormone (LH) and FSH were measured daily by radioimmunoassay and size and number of follicles were assessed by ultrasonography. Follicle-stimulating hormone in group A (80 mm less than or equal to maxD) was significantly higher than those of group B (60 mm less than or equal to maxD less than 80 mm) and C (maxD less than 60 mm) for the last 4 days of the treatment. This FSH rise in group A was not accounted for by FSH accumulation by the study of pharmacodynamics, and so was thought to be of endogenous origin. Luteinizing hormone was also elevated 3 days before the administration of human chorionic gonadotropin (hCG) in both groups A and B. The number of follicles in group A at hCG administration was significantly greater than that of group C. Any significant differences were not found in either total amount of purified urinary FSH or in the basal FSH and the LH levels before treatment of the three groups. These results suggest that excessive ovarian enlargement during gonadotropin therapy is caused by multiple follicular development primarily stimulated by endogenous FSH. Endogenous LH release further enhances ovarian enlargement. PMID- 1898894 TI - Adjusting the dose to the individual response of the patient during the induction of ovulation with pulsatile gonadotropin-releasing hormone. AB - To identify the effective dose of intravenous pulsatile gonadotropin-releasing hormone necessary to induce ovulation in patients with chronic anovulation of diverse etiology, 40 women were subdivided into four groups: idiopathic hypogonadotropic hypogonadism (IHH), functional hypothalamic amenorrhea, normoandrogenic oligomenorrhea, and polycystic ovarian syndrome (PCOS). During 90 treatment cycles, the dose was the only parameter that was progressively adjusted. The overall ovulation rate per cycle was 100% in IHH, functional hypothalamic amenorrhea, and normoandrogenic oligomenorrhea, using only 5 micrograms/90 minutes in functional hypothalamic amenorrhea and normoandrogenic oligomenorrhea and up to 7.5 micrograms/90 minutes in IHH. In PCOS, the ovulation rate was 67.6%, using up to 20 micrograms/90 minutes. The lesser degree of effectiveness observed in PCOS can probably be explained by the different basal endocrine profile presented by these subjects. PMID- 1898895 TI - The luteal phase after oocyte recovery in a spontaneous cycle. AB - There is disagreement as to whether follicular aspiration and oocyte recovery leads to a defective luteal phase. A group of 20 women with mild endometriosis was studied over two consecutive spontaneous cycles. Follicular aspiration and oocyte recovery was performed 32 hours after the onset of the endogenous luteinizing hormone surge during the second cycle. There was little disturbance of the luteal phase or in the pituitary gonadal relationship in the aspirated cycle. Although a significantly lower serum progesterone was noted on day 8 of post-oocyte recovery, all results were within the normal range seen in the control cycles. PMID- 1898896 TI - A protective human monoclonal antibody directed to the outer core region of Pseudomonas aeruginosa lipopolysaccharide. AB - The protective activity against experimental Pseudomonas aeruginosa infection of a human monoclonal antibody, MH-4H7, which is thought to recognize L-rhamnose and its neighboring residues in the outer core region of P. aeruginosa lipopolysaccharide and which binds to strains of Homma serotypes A, F, G, H, K, and M, was studied in normal, burned, and leukopenic mice. MH-4H7 at doses of 0.1 to 1.0 micrograms per mouse (5 to 50 micrograms/kg) was effective against serotype A, F, G, H, and K clinical isolates of P. aeruginosa tested in normal mice but not against strains of serotype M, B, E, or I. The 50% protective doses were calculated to be 0.01 and 0.1 micrograms per mouse against challenge with serotype G strains and 3 to 8 micrograms per mouse against challenge with serotype A strains. MH-4H7 promoted macrophage-mediated opsonophagocytosis of serotype A, F, G, H, and K strains but not of serotype M strains. The opsonophagocytic activity, expressed as the reduction rate of viable bacteria in the presence of MH-4H7, macrophages, and complement, was higher against serotype G strains (more than 90%) than against serotype A strains (60 to 80%) and serotype F, H, and K strains (50 to 86%). It was correlated with the protective activity but not with the binding intensity of MH-4H7 to the organisms. In addition, burned and leukopenic mice as well as normal mice infected with serotype G strains recovered from a very low dosage of MH-4H7. Thus, a monoclonal antibody directed to the outer core region of P. aeruginosa lipopolysaccharide was effective against infection with a wide range of O-serotype strains of P. aeruginosa. PMID- 1898897 TI - Diphosphoryl lipid A derived from lipopolysaccharide (LPS) of Rhodopseudomonas sphaeroides inhibits activation of 70Z/3 cells by LPS. AB - Diphosphoryl lipid A derived from nontoxic lipopolysaccharide (LPS) of Rhodopseudomonas sphaeroides ATCC 17023 did not stimulate the murine pre-B cell line 70Z/3 to synthesize surface immunoglobulin or kappa mRNA. However, it effectively blocked Escherichia coli LPS-induced activation of 70Z/3 cells in a concentration-dependent manner. This inhibition was specific only to cells activated by LPS, since it did not inhibit activation of 70Z/3 cells by gamma interferon. Maximal inhibitory effect occurred when the antagonist was added within 2 h before adding the LPS. These results strongly suggested that R. sphaeroides diphosphoryl lipid A is competing with E. coli LPS for physiological lipid A receptors on the 70Z/3 cells. PMID- 1898898 TI - Functional role of mucoid exopolysaccharide (alginate) in antibiotic-induced and polymorphonuclear leukocyte-mediated killing of Pseudomonas aeruginosa. AB - We evaluated in vitro the functional role of mucoid exopolysaccharide (MEP) of Pseudomonas aeruginosa in blocking antibiotic-induced and polymorphonuclear leukocyte (PMN)-mediated pseudomonal killing. The serum-resistant P. aeruginosa isolates used were mucoid strain 144MR and its nonmucoid revertant, strain 144NM. By timed kill curves, early bacterial effects of amikacin against mucoid strain 144MR were substantially less than those observed with nonmucoid strain 144NM; this effect was reversible with enzymatic hydrolysis of MEP of strain 144MR by alginase. Also, early tobramycin uptake (15 to 30 min) by mucoid 144MR cells was less than that seen with nonmucoid strain 144NM; pretreatment of 144MR cells with alginase substantially enhanced early tobramycin uptake compared with untreated 144MR cells (P = 0.08). In strain 144NM (but not in strain 114MR) there was a notable postantibiotic leukocidal enhancement effect manifested by increased nonopsonic killing following brief exposure of these cells to supra-MIC amikacin; pretreatment of strain 144MR with alginase rendered these cells more susceptible to amikacin-induced postantibiotic leukocidal enhancement. Similarly, direct PMN mediated nonopsonic killing of mucoid strain 144MR was significantly less than that observed with strain 144NM (P less than 0.05); pretreatment of 144MR cells with alginase rendered this strain equal to strain 144NM in susceptibility to nonopsonic killing. In addition, exogenous sodium alginate or extracted MEP of strain 144MR interfered with effective nonopsonic killing of strain 144NM by PMNs. Studies also indicated that mucoid strain 144MR was phagocytosed significantly less well than its nonmucoid mate (P less than 0.00001), an effect reversed by pretreatment of the mucoid cells with alginase. These data confirm that P. aeruginosa MEPs functionally decrease the uptake and early bactericidal effect of aminoglycosides in vitro and interfere with effective PMN-mediated nonopsonic phagocytosis and killing of mucoid strains. PMID- 1898899 TI - Isolation and partial characterization of major protein antigens in the culture fluid of Mycobacterium tuberculosis. AB - Five actively secreted proteins (MPT32, MPT45, MPT51, MPT53, and MPT63) and the MPT46 protein were purified to homogeneity from Mycobacterium tuberculosis culture fluid and compared with proteins previously purified by ourselves and other investigators. Antisera were obtained by immunization of rabbits with all of the newly isolated proteins identified to be immunogenic. Two-dimensional electrophoresis of culture fluids obtained each week for 2 to 10 weeks of culturing of M. tuberculosis revealed characteristic changes, permitting identification of two distinct groups of proteins being actively secreted from the mycobacterial cells or appearing later in the culture fluids as a result of the release of soluble proteins from the cytosol after lysis of bacteria. The N terminal amino acid sequences of five MPTs were shown to be identical to those of proteins previously isolated by other investigators and given different designations, and five new sequences are given. These sequences and the use of the antisera may serve to identify these proteins with mycobacterial constituents isolated by other investigators. The previously identified but not isolated MPT45 protein was shown to correspond to the C component of the antigen 85 complex. The 27-kDa MPT51 protein was demonstrated to cross-react with the three components of the antigen 85 complex, and the N-terminal amino acid sequences of MPT51 and MPT59 showed 60% homology. This finding and the extensive cross-reactivity between the components of the antigen 85 complex may indicate that there is a family of closely related secreted proteins in mycobacteria. PMID- 1898900 TI - Prostaglandin E release from human monocytes treated with lipopolysaccharides isolated from Bacteroides intermedius and Salmonella typhimurium: potentiation by gamma interferon. AB - The purpose of this investigation was to examine gamma interferon potentiation of lipopolysaccharide (LPS) responses in human monocytes by using phenol-water extracted (unfractionated) and highly purified LPS preparations isolated from Bacteroides intermedius and Salmonella typhimurium. Phenol-water-extracted LPS preparations from these bacteria were further purified by chromatography over Sepharose-CL-4B. LPS enrichment in pooled column fractions was assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and quantitation of hydroxy fatty acid and 2-keto-3-deoxyoctulosonic acid content, protein contamination, and anthrone-reactive material. Monocyte stimulation by LPS, measured as prostaglandin E (PGE) release, was assessed with and without gamma interferon treatment. Cells were either treated simultaneously with gamma interferon and LPS or pretreated with gamma interferon prior to LPS stimulation. PGE release from counterflow-isolated monocytes was quantitated during the 0- to 24-h and 24- to 48-h culture intervals. Contrary to previous results from this laboratory, phenol water-extracted LPS preparations from B. intermedius and S. typhimurium were similar in their capacities to stimulate PGE release from monocytes. Molecular sieve chromatography was found to remove substantial amounts of high-molecular weight polysaccharide contaminants only from the B. intermedius LPS but did not significantly alter the potency of either B. intermedius or S. typhimurium LPS. Gamma interferon cotreatment did not potentiate the release of PGE with any of the LPS preparations tested. However, 24-h pretreatment of monocytes with gamma interferon followed by a 24-h exposure to LPS resulted in significant potentiation of PGE release over LPS alone. In addition, B. intermedium preparations were approximately threefold more potent than similarly prepared LPS isolates from S. typhimurium following gamma interferon pretreatment. These results indicate that gamma interferon can selectively potentiate the effects of B. intermedius LPS in human monocyte isolates. PMID- 1898901 TI - Synthesis and characterization of a Pseudomonas aeruginosa alginate-toxin A conjugate vaccine. AB - Alginate from Pseudomonas aeruginosa 3064 was depolymerized by controlled heating in dilute acid. The resulting depolymerized alginate (Mr less than 60,000) was covalently coupled to toxin A with adipic acid dihydrazide as a spacer molecule and carbodiimide as a linker. The resulting conjugate was composed of toxin A and depolymerized alginate at a ratio of 4:1 and possessed an Mr of 260,000. The conjugate was nontoxic and nonpyrogenic. While native alginate (Mr greater than 640,000) given in a range of doses was poorly immunogenic in mice and rabbits, the conjugate induced high levels of antibody which bound to native alginate. Rabbits, but not mice, also produced an antitoxin immunoglobulin antibody response. Alginate derived from three other strains of P. aeruginosa competed with the homologous 3064 alginate for binding to anticonjugate antibody. This indicates that the conjugate elicits an antibody response able to recognize heterologous alginates. The serum from rabbits immunized with the conjugate was effective at promoting the uptake and killing of mucoid strains of P. aeruginosa by human polymorphonuclear leukocytes. In contrast, immunization with native alginate did not engender an opsonic antibody response. Rabbit anticonjugate antibody also neutralized the cytotoxic potential of toxin A. PMID- 1898902 TI - CD4+ and CD8+ T lymphocytes both contribute to acquired immunity to blood-stage Plasmodium chabaudi AS. AB - In the present study, the contribution of CD4+ and CD8+ T lymphocytes to acquired immunity to blood-stage infection with the murine malaria species Plasmodium chabaudi AS was investigated. C57BL/6 mice, which are genetically resistant to infection with this hemoprotozoan parasite and exhibit a transient course of infection, were treated intraperitoneally with monoclonal antibodies to T-cell epitopes, either anti-Thy-1, anti-CD4, or anti-CD8. After intraperitoneal infection with 10(6) parasitized erythrocytes, control C57BL/6 mice exhibited a peak parasitemia on day 9 of approximately 35% parasitized erythrocytes and eliminated the infection within 4 weeks. Mice depleted of Thy-1+ or CD4+ T cells had significantly higher parasitemias on day 7 as well as significantly higher peak parasitemias. These mice were unable to control the infection and developed a persistent, high parasitemia that fluctuated between 40 and 60% until the experiment was terminated on day 56 postinfection. Depletion of CD8+ T lymphocytes was found to have no effect on the early course of parasitemia or on the level of peak parasitemia. However, mice depleted of CD8+ T cells experienced two recurrent bouts of parasitemia during the later stage of the infection and required more than 5 weeks to eliminate the parasites. After the peak parasitemia, which occurred in control and experimental animals on day 9, there was a sharp drop in parasitemia coinciding with a wave of reticulocytosis. Therefore, the contribution of the influx of reticulocytes, which are not the preferred host cell of this hemoprotozoan parasite, to limiting the parasitemia was also examined by determining the course of reticulocytosis during infection in control and T cell-depleted animals. Early in infection, there was a marked and comparable reticulocytosis in the peripheral blood of control and T cell depleted mice; the reticulocytosis peaked on day 12 and coincided with the dramatic and sudden reduction in parasitemia occurring in all groups. In both control and CD8-depleted mice the percentage of reticulocytes decreased as the infection was resolved, whereas in CD4-depleted mice marked reticulocytosis correlated with high, persistent parasitemia. These results thus demonstrate that both CD4+ and CD8+ T cells are involved in acquired immunity to blood-stage P. chabaudi AS and that the influx of reticulocytes into the blood that occurs just after the peak parasitemia may contribute temporarily to limiting the parasitemia. PMID- 1898904 TI - Environmental conditions which influence mucoid conversion Pseudomonas aeruginosa PAO1. AB - Growth and conversion to the mucoid phenotype by nonmucoid Pseudomonas aeruginosa PAO1 was studied in a chemostat system under conditions designed to reflect those likely to be present during chronic infection in the lung in cystic fibrosis patients. Mucoid variants were consistently isolated during continuous culture in the presence of 0.3 M NaCl or 5 or 10% glycerol. Mucoid subpopulations were also detected under conditions of carbon, nitrogen, or phosphate limitation. During carbon or nitrogen limitation, mucoid conversion was dependent upon the choice of substrate. Phosphate-limited cultures exhibited an inverse relationship between culture growth rate and number of mucoid organisms detected. Mucoid variants were not detected when dilution rates (D) exceeded 0.173 h-1. Conversely, at a D of 0.044 h-1, 40% of the population expressed the mucoid phenotype. Phosphorylcholine, a product of phospholipase C activity on the major lung surfactant phosphatidylcholine, was also used as a growth substrate in nutrient limitation studies. Under all conditions, growth of PAO1 supplied with phosphorylcholine resulted in isolation of mucoid variants, indicating that the lung may provide at least one nutrient source conducive to mucoid conversion. Continuous culture also resulted in detection of a phage associated with strain PAO1. High titers of phage were present under all conditions, including those which yielded no mucoid organisms, suggesting that environmental conditions rather than the phage regulated the appearance of mucoid variants. PMID- 1898903 TI - Molecular cloning, sequencing, and identification of a metalloprotease gene from Listeria monocytogenes that is species specific and physically linked to the listeriolysin gene. AB - The entire nucleotide sequence of an open reading frame located immediately downstream of the listeriolysin gene from a virulent Listeria monocytogenes serotype 1/2a strain was determined. The product of the open reading frame was 510 amino acids with a predicted molecular weight of 57,400. The deduced amino acid sequence of this open reading frame is highly similar to that of a family of secreted metalloproteases produced by various members of the genus Bacillus, of which thermolysin is the prototype. Immunoblots performed with specific antisera raised against thermolysin from Bacillus stearothermophilus allowed the detection of a 60-kDa polypeptide, corresponding to the pro-form of the protease, in culture supernatants of L. monocytogenes strains. In maxicell experiments, Escherichia coli recombinants harboring this open reading frame also specifically directed production of a 60-kDa protein. Protease activity was low to undetectable in both Listeria strains and E. coli recombinants. This is due to lack of processing of the inactive pro-form of the protease to its mature active form in both species. We have designated this gene mpl for metalloprotease of L. monocytogenes. The gene was present only in pathogenic L. monocytogenes strains, in which it was physically linked to the listeriolysin gene. PMID- 1898905 TI - A monoclonal antibody to gamma interferon blocks augmentation of natural killer cell activity induced during systemic cryptococcosis. AB - These studies demonstrate that the cytotoxic activity of splenic natural killer (NK) cells is augmented in both nu/nu and nu/+ mice during systemic cryptococcosis. Both the kinetics and the regulation of NK cell activity differed in Cryptococcus neoformans-infected nu/nu and nu/+ mice. Greater augmentation was observed following challenge with 10(5) cells than with smaller inocula, and augmented NK cell activity was not always associated with enhanced control of systemic cryptococcosis. Infection with a nonencapsulated strain of C. neoformans induced an early but transient increase in splenic NK cell activity in nu/nu and nu/+ mice. Injection of capsular polysaccharide induced a transient augmentation of splenic NK cell activity in nu/+ mice but caused a persistent increase in splenic NK cell activity in nu/nu mice. In vivo treatment with monoclonal antibody to gamma interferon abrogated the augmentation of splenic NK cell activity induced during cryptococcal infections in both nu/nu and nu/+ mice and enhanced the susceptibility of nu/+ mice to C. neoformans to a greater extent than it did that of nu/nu mice. These results suggest that gamma interferon is an important mediator of resistance to C. neoformans. PMID- 1898906 TI - Limited clonal heterogeneity of antigen-specific T cells localizing in the pleural space during mycobacterial infection. AB - To detect possible differences in phenotype and fine specificity for mycobacterial antigens between CD4-positive T cells from peripheral blood (PB) and from inflammatory sites, we identified four patients presenting with a mycobacterial pleural exudate (PE) rich in PPD-specific lymphocytes and with a negative skin test to tuberculin purified protein derivative (PPD) and a negative proliferative response of PB lymphocytes to PPD at the same time. Several weeks after chemotherapy, these patients converted to PPD responsiveness in the periphery, and PPD-specific clones could be generated from PB at this stage. The phenotypic comparison of PE lymphocytes and concomitant PB lymphocytes obtained before treatment showed an increase of CD8 cells and a high frequency of HLA-DR positive activated T cells in PE. The frequency of tetanus toxoid-specific and Candida albicans-specific proliferating T cells was lower than that of PPD specific cells in PE but not in PB. PPD-specific clones were derived initially from PE and from PB once the patients had converted to PPD responsiveness. The two sets of clones from each patient were compared for proliferative response to mycobacterial antigen clusters of defined molecular weight ranges. A large number of PE-derived clones (36%) responded to a fraction of 27 to 35 kDa, whereas only one clone from PB responded to the same fraction. The purified antigen P32 (32 kDa), a soluble mycobacterial protein, stimulated PE-derived clones that were responsive to the 37- to 27-kDa fraction but did not stimulate PB-derived clones. The data demonstrate that PE- and PB-derived lymphocytes differ both in phenotype and in fine specificity, suggesting a limited clonal heterogeneity of T cells localizing at the inflammatory site in tuberculous patients without a PPD response in the periphery. Therefore T cells compartmentalized at inflammatory sites provide information that is different from that provided by T cells in the periphery. PMID- 1898907 TI - Mechanism for candidacidal activity in macrophages activated by recombinant gamma interferon. AB - Candidacidal activity in macrophages activated by recombinant gamma interferon was examined kinetically in relation to acidification of phagolysosomes. In resident peritoneal macrophages (PMPs) of BALB/c mice, enhanced killing activity against Candida albicans was demonstrated after incubation with 100 U of gamma interferon per ml for 24 h but not after incubation for 48 to 72 h. Conversely, increased generation of H2O2 was exhibited in PMPs incubated from 48 to 72 h but not in PMPs incubated for 24 h. In normal PMPs, fusion of lysosomes to candida containing phagosomes was readily accomplished and phagosome-lysosome fusion was not enhanced further by activation. The candidacidal substance was extracted from granule-rich fractions of either normal or activated PMPs by using citric acid (pH 2.7) in equal amounts; the substance showed a noncationic, heat-stable protein nature. In addition, when phagolysosomal pH was determined by flow cytometry of intraphagolysosomal fluorescein isothiocyanate-labeled C. albicans, phagolysosomes with low pH (less than 4.0) were detected in about 40% of PMPs activated for 24 h but not in those activated for 72 h or in normal PMPs. Moreover, increasing the intralysosomal pH with NH4Cl resulted in a significant reduction of candidacidal activity in activated PMPs. These results indicate that the candidacidal activity of gamma interferon-activated PMPs correlates well with enhanced acidification of their phagolysosomes and suggest that the candidacidal activity of activated PMPs is independent from reactive oxygen molecules and is mediated by proteinaceous substance(s) generated only in a strong acidic milieu of phagolysosomes by activation. PMID- 1898908 TI - Inhibitory activity on bacterial motility and in vivo protective activity of human monoclonal antibodies against flagella of Pseudomonas aeruginosa. AB - Three stable hybridoma cell lines, IN-2A8, IN-5D6, and ZI-3A8, that secrete human monoclonal antibodies (MAbs) specific for b-type flagella of Pseudomonas aeruginosa were established by fusing peripheral blood lymphocytes from healthy volunteers with murine myeloma P3X63-Ag8.653 cells. The immunoglobulin M MAbs reacted specifically with flagellin (Mr, 52,000) by Western blotting (immunoblotting) analysis and bound specifically to clinical isolates belonging to Homma serotypes A, B, H, I, and M at frequencies of 58, 50, 46, 30, and 35%, respectively, but did not bind to any serotype E or G isolates. Overall, the MAbs bound to 31% of the clinical isolates. MAb IN-2A8 strongly protected burned mice challenged with P. aeruginosa bearing b-type flagella from death following parenteral administration of 0.1 microgram per mouse. This MAb also inhibited P. aeruginosa colony spreading in soft agar at a concentration of more than 1 microgram/ml but only slightly enhanced opsonophagocytosis by human polymorphonuclear leukocytes. A line of evidence suggests that the potent in vivo activity of MAb IN-2A8 in the burned-mouse model is likely to be caused by its inhibition of bacterial motility after binding to flagella. PMID- 1898909 TI - Immunomodulation of mouse macrophage killing of Mycobacterium avium in vitro. AB - When C57BL/6 mice were infected intravenously with Mycobacterium avium, bacterial growth continued within the spleen until more than 10(8) CFU/g of tissue were attained. This contrasted with Mycobacterium bovis BCG infections where growth declined after 2 weeks. In vivo M. avium-infected splenic macrophages were harvested from chronically infected mice and cultured in vitro for 4 days at 37 degrees C. The number of viable mycobacteria within the resulting macrophage monolayers decreased when cultured in the presence of autologous sensitized T cells and an exogenous source of interleukin-2 (recombinant interleukin-2; 50 U/ml) compared with untreated controls (P less than 0.05). Incubation of the infected macrophages with autologous T cells and soluble M. avium antigens also significantly reduced the number of viable organisms. These results indicate that the mycobactericidal activity of M. avium-infected macrophages can be enhanced in a way that may have important therapeutic implications for patients infected with this opportunistic pathogen. PMID- 1898910 TI - Gamma interferon-mediated inhibition of Eimeria vermiformis growth in cultured fibroblasts and epithelial cells. AB - The growth of Eimeria vermiformis within cultured murine fibroblastlike (L-929) or rat epithelial-like (RATEC) cells was inhibited by treatment of the cells with the appropriate recombinant gamma interferon. The effect was apparent as a reduction in both the initial numbers of intracellular sporozoites and, to a much greater extent, the numbers of subsequent developmental stages. Pretreatment of the host cells was more effective than treatment in the early postinvasive period, and recombinant gamma interferon had no effect on the development of the parasite if added 24 h or later after the inoculation of sporozoites. Incubation of sporozoites in medium containing recombinant gamma interferon in no way affected their ability to invade or to grow within host cells. These findings indicate that the inhibitory effects of recombinant gamma interferon on the growth of E. vermiformis are mediated via the host cell and are directed mainly against the transforming sporozoite, although the ability of the sporozoite to invade the host cell was also reduced to some extent. The later developmental stages were refractory to the effects of this lymphokine. PMID- 1898911 TI - Human immune response to Mycobacterium tuberculosis antigens. AB - Little is known about the immunodominant or protective antigens of Mycobacterium tuberculosis in humans. Cell-mediated immunity is necessary for protection, and healthy tuberculin-positive individuals are relatively resistant to exogenous reinfection. We compared the targets of the cell-mediated immune response in healthy tuberculin-positive individuals to those of tuberculosis patients and tuberculin-negative persons. By using T-cell Western blotting (immunoblotting) of nitrocellulose-bound M. tuberculosis culture filtrate, peaks of T-cell blastogenic activity were identified in the healthy tuberculin reactors at 30, 37, 44, 57, 64, 71 and 88 kDa. Three of these fractions (30, 64, and 71 kDa) coincided with previously characterized proteins: antigen 6/alpha antigen, HSP60, and HSP70, respectively. The blastogenic responses to purified M. tuberculosis antigen 6/alpha antigen and BCG HSP60 were assessed. When cultured with purified antigen 6/alpha antigen, lymphocytes of healthy tuberculin reactors demonstrated greater [3H]thymidine incorporation than either healthy tuberculin-negative controls or tuberculous patients (8,113 +/- 1,939 delta cpm versus 645 +/- 425 delta cpm and 1,019 +/- 710 delta cpm, respectively; P less than 0.01). Healthy reactors also responded to HSP60, although to a lesser degree than antigen 6/alpha antigen (4,276 +/- 1,095 delta cpm; P less than 0.05). Partially purified HSP70 bound to nitrocellulose paper elicited a significant lymphocyte blastogenic response in two of six of the tuberculous patients but in none of the eight healthy tuberculin reactors. Lymphocytes of none of five tuberculin-negative controls responded to recombinant antigens at 14 or 19 kDa or to HSP70. Antibody reactivity generally was inversely correlated with blastogenic response: tuberculous sera had high titer antibody to M. tuberculosis culture filtrate in a range from 35 to 180 kDa. This is the first systematic evaluation of the human response to a panel of native and recombinant antigens in healthy tuberculin reactors and tuberculous patients. Antigens which stimulated prominent lymphocyte blastogenic responses were identified in seven fractions on T-cell Western blot analysis. Two of these may represent previously characterized proteins; the others may contain immunodominant proteins that will require further characterization. PMID- 1898912 TI - Mycobacterium leprae renders Schwann cells and mononuclear phagocytes susceptible or resistant to killer cells. AB - Acquired resistance to Mycobacterium leprae, the etiologic agent of leprosy, crucially depends on cellular immune mechanisms. In addition to interleukin mediated helper functions, killer mechanisms seem to be involved. This study addresses the question of how M. leprae render mononuclear phagocytes and Schwann cells, its natural targets, susceptible or resistant to killer cells. Killer activities were stimulated in peripheral blood mononuclear cells from healthy individuals by incubation with mycobacteria plus interleukin-2. These cells lysed Schwann cells and mononuclear phagocytes which had been pulsed with dead M. leprae, while unpulsed targets remained virtually unaffected. Importantly, targets infected with viable M. leprae were not lysed; furthermore, infection with viable M. leprae as well as gamma interferon stimulation or heat shock caused resistance in otherwise susceptible targets which had been pulsed with dead M. leprae. Thus, M. leprae markedly influenced the effect of killer cells on Schwann cells and mononuclear phagocytes. PMID- 1898913 TI - Endotoxin shedding by enterobacteria: free and cell-bound endotoxin differ in Limulus activity. AB - The endotoxin activities of gram-negative bacteria and their lipopolysaccharides (LPS) have been quantitated by a chromogenic Limulus amocbocyte lysate (CLAL) assay. When bacterial cell exposing various cell surface structures were compared, the highest Limulus activities were found in R strains of Escherichia coli and Salmonella typhimurium mutants. E. coli with K antigens did not differ from K-negative strains. By measuring beta-hydroxymyristic acid (3-OH tetradecanoic acid, beta-OHC14:0), it was possible to compare the CLAL activities of LPS bound to bacterial cells, LPS shed into the culture medium, and purified LPS. After 16 h of growth, the cell-free culture supernatants of three E. coli O1K1 strains and S. typhimurium showed CLAL activities 14.3 to 20.3 times higher than did the corresponding bacterial cell suspensions in relation to their beta OHC14:0 contents. Four other E. coli strains (O serotypes O14, O24, and O75) and the S. typhimurium 395 R mutants MR5 and MR6 showed CLAL values 2.8 to 7.9 times higher in their culture supernatants. LPS of E. coli O1K1 and S. typhimurium had lower CLAL activities than the culture supernatants (1/10 and 1/4, respectively). Although the beta-OHC14:0 concentrations of the culture supernatants were approximately half those of the corresponding bacterial cells, all had CLAL values that were 2 to 21 times higher. The bacterial cell suspension, culture supernatant, and purified LPS of S. typhimurium MS were compared by CLAL assay and a quantitative enzyme-linked immunosorbent assay based on monoclonal antibodies to the O5 antigen. Endotoxin shed into the culture medium was the most CLAL-active form of LPS, while purified LPS was the most antigen-active form. The results emphasize the importance of appropriate standards when quantifying endotoxin in various states. In conclusion, E. coli and S. typhimurium bacteria shed significant amounts of endotoxin into the surrounding medium during growth. This form of LPS is more CLAL active than the cell-bound or purified LPS. PMID- 1898914 TI - Modulation of Mycobacterium lepraemurium growth in murine macrophages: beneficial effect of tumor necrosis factor alpha and granulocyte-macrophage colony stimulating factor. AB - Mycobacterium lepraemurium grew progressively in monolayers of Proteose Peptone elicited macrophages from C57BL/6 mice. Treatment of macrophage monolayers with gamma interferon led to an enhancement of growth of M. lepraemurium in macrophages. Treatment with tumor necrosis factor alpha or granulocyte-macrophage colony-stimulating factor led to restriction of mycobacterial growth in macrophages. PMID- 1898915 TI - Identity between polysaccharide antigens of Moraxella nonliquefaciens, group B Neisseria meningitidis, and Escherichia coli K1 (non-O acetylated). AB - A surface polysaccharide antigen of Moraxella nonliquefaciens, reported to be cross-reactive with the capsular polysaccharides of group B Neisseria meningitidis and Escherichia coli K1 (K. Blvre, K. Bryn, O. Closs, N. Hagen, and L. O. Froholm, NIPH Ann. 6:65-73, 1983), was isolated, purified, and characterized chemically, immunologically, and by nuclear magnetic resonance. This polysaccharide was shown to be a linear homopolymer of alpha (2----8)-linked N-acetylneuraminic acid, identical to the capsular polysaccharide of group B N. meningitidis and O-acetyl-negative variants of E. coli K1. PMID- 1898916 TI - Inhibition of intracellular growth of Histoplasma capsulatum yeast cells by cytokine-activated human monocytes and macrophages. AB - Human monocytes/macrophages (M psi) were infected with Histoplasma capsulatum yeast cells, and intracellular growth was quantified after 24 h of incubation in medium alone or in medium containing cytokines. Yeast cells multiplied within freshly isolated monocytes, cultured M psi, and alveolar M psi with intracellular generation times of 14.2 +/- 1.4, 18.5 +/- 2.1, and 19.9 +/- 1.9 h (mean +/- standard error of the mean), respectively. Monocytes and M psi inhibited the intracellular growth of yeast cells in response to cytokine supernatant; maximum inhibition was obtained when cytokines were added to cell monolayers immediately after infection. Opsonization of yeast cells in normal serum or in H. capsulatum immune serum did not affect the intracellular generation time of yeast cells in either control M psi or cytokine-activated M psi. PMID- 1898917 TI - Penetration and binding of aldose-reductase inhibitors in the lens. AB - Diffusion, partitioning, and binding of two aldose-reductase inhibitors (ARI) in the rat lens were investigated under in vitro conditions. A lipophilic ARI (CT 112) and a hydrophilic ARI (AD-5467) were used as model drugs. Under lens-uptake conditions, the drug concentration in the lens increased rapidly during the initial 10 hr and reached steady state (equilibrium) after 24 hr. Despite the equilibrium concentration of CT-112 in the lens which is approximately three times of that of AD-5467, the inhibition rate of CT-112 against the accumulation of sugar alcohols was appreciably lower than that for AD-5467. The equilibrium concentration in the lens after the penetration/binding experiment also suggested that AD-5467 may interact with the target sites of enzymes more than that for CT 112. The time course of the lens concentration during the uptake and desorption experiments was well described by a diffusion/binding model assuming a Langmuir binding. The diffusion coefficient, the partition coefficient, and binding parameters in the rat lens were determined for the two ARIs. PMID- 1898919 TI - Transformation of the phytopathogenic bacterium Clavibacter michiganense subsp. michiganense by electroporation and development of a cloning vector. AB - We constructed a cloning vector for use in the plant pathogenic bacterium Clavibacter michiganense subsp. michiganense. The vector pDM100 consists of a 3.2 kb restriction fragment of the Clavibacter plasmid pCM1 joined to a pBR325 derivative carrying the neomycin phosphotransferase of transposon Tn5 and the gentamicin acetyltransferase of Tn1696. Both antibiotic resistance genes are efficiently expressed in C. michiganense subsp. michiganense. Although polyethylene glycol-mediated transfection of spheroplasts with the DNA of the C. michiganense subsp. michiganense-specific bacteriophage CMP1 yielded about 3 x 10(3) transfectants per microgram of DNA, in transformations with plasmid DNA only a very few transformants were obtained. However, the transformation efficiency could be improved by electroporation of intact cells, giving about 2 x 10(3) transformants per microgram of plasmid DNA. Since a transformation procedure and a cloning vector are now available, pathogenicity in C. michiganense subsp. michiganense can now be analyzed genetically. PMID- 1898920 TI - Mechanical properties of Bacillus subtilis cell walls: effects of removing residual culture medium. AB - Experiments are described in which the tensile strength, the initial (Youngs') modulus, and other mechanical properties of the bacterial cell wall were obtained as functions of relative humidity (RH) in the range of 20 to 95%. These properties were deduced from tensile tests on bacterial thread, a fiber consisting of many highly aligned cells of Bacillus subtilis, from which residual culture medium had been removed by immersion in water. Reasons are given to support the idea that the mechanical properties of bacterial thread relate directly to those of the cylinder wall and that they are not influenced by septa, cytoplasm, or the thread assembly. The data show that the cell wall, like many other heteropolymers, is visco-elastic. When dry, it behaves like a glassy polymer with a tensile strength of about 300 MPa and a modulus of about 13 GPa. When wet, its behavior is more like a rubbery polymer with a tensile strength of about 13 MPa and a modulus of about 30 MPa. Thus, the cell wall is stronger than previously reported. Walls of this strength would be able to bear a turgor pressure of 2.6 MPa (about 26 atm). The dynamic behavior suggests a wide range of relaxation times. The way in which mechanical behavior depends strongly on humidity is discussed in terms of possible hydrogen bond density and the ordering of water molecules. Cell walls in threads containing residual culture medium TB are, except at low RH, 10 times more flexible and about 4 times less strong. All of their mechanical properties appear to vary with change in RH in a manner similar to those of walls from which the culture medium has been washed, but with a downshift of about 18% RH. PMID- 1898918 TI - Fnr mutants that activate gene expression in the presence of oxygen. AB - The regulatory protein Fnr is required for anaerobic expression of several anaerobic respiratory enzymes in Escherichia coli. To gain insight into how Fnr activity is regulated by oxygen, we have isolated Fnr mutants that increase expression of the nitrate reductase operon in the presence of oxygen (Fnr* mutants). Seven single-amino-acid substitutions that mapped within two regions of Fnr have been characterized. Two mutants mapped adjacent to two Cys residues in the N-terminal Cys cluster. Five Fnr* substitutions mapped to a region of Fnr that is similar to the cyclic AMP-binding domain of the catabolite activator protein (CAP). Within this group, four mutants were clustered in a region analogous to the CAP C helix, which is important in CAP dimer subunit interactions. Taken together, these data implicate regions in Fnr that may be important either in sensing oxygen deprivation or in the conformational change proposed to be necessary for Fnr activation under anaerobic conditions. PMID- 1898921 TI - Mechanical properties of Bacillus subtilis cell walls: effects of ions and lysozyme. AB - Bacterial threads of Bacillus subtilis have been immersed in, and redrawn from, water of various pH values, in solutions of (NH4)2SO4 and NaCl of various concentrations, and in lysozyme solutions. The changes in the tensile strength, elastic modulus, and other mechanical properties of the bacterial cell wall due to these treatments were obtained. The data show that change in pH has little effect but that as the salt concentration is increased, the cell walls become more ductile. A high salt concentration (1 M NaCl) can reduce the modulus by a factor of 26 to 13.5 MPa at 81% relative humidity and the strength by a factor of only 2.5. Despite attacking the septal-wall region of the cellular filaments, lysozyme has no effect on the mechanical properties. There is no significant change in the stress relaxation behavior due to any of the treatments. The dependence of mechanical properties on the salt concentration is discussed in terms of the polyelectrolyte nature of cell walls. The evidence presented in this and the accompanying paper (J. J. Thwaites and U.C. Surana, J. Bacteriol., 173:197-203, 1991) supports the idea that the peptidoglycan in bacterial cell wall is an entanglement network with a large degree of molecular flexibility, with some order but no regular structure. PMID- 1898922 TI - DAL82, a second gene required for induction of allantoin system gene transcription in Saccharomyces cerevisiae. AB - Several highly inducible enzyme activities are required for the degradation of allantoin in Saccharomyces cerevisiae. Induction of these pathway enzymes has been shown to be regulated at transcription, and response to inducer is lost in dal81 and dal82/durM mutants. The similar phenotypes generated by dal81 and dal82 mutations prompted the question of whether they were allelic. We demonstrated that the DAL81 and DAL82 loci are distinct, unlinked genes situated on chromosomes IX and XIV. DAL82 gene expression did not respond to induction by the allantoin pathway inducer or to nitrogen catabolite repression. Expression was also not significantly affected by mutation of the dal80 locus. From the nucleotide sequence of the DAL82 gene, we deduced that it encodes a protein with a mass of 29,079 Da that may possess the structural motifs expected of a regulatory protein. This protein was shown to be required for the function mediated by the cis-acting upstream induction sequence situated in the 5' flanking regions of the inducible allantoin pathway genes. PMID- 1898923 TI - Effect of signal sequence alterations on export of levansucrase in Bacillus subtilis. AB - A series of alterations in the Bacillus amyloliquefaciens levansucrase signal peptide were made by in vitro mutagenesis, and their effect on the secretion of levansucrase in Bacillus subtilis was studied. Some of the alterations resulted in a completely defective signal peptide. These included the removal of positively charged residues from the N-terminus and disruption of the hydrophobic core of the signal peptide either by introducing a charged residue or by deleting five or more amino acids. Analysis of the signal peptide processing-site alterations revealed that small residues are preferred at the -1 and -3 positions. However, a wide variety of amino acids are tolerated at the +1 position. PMID- 1898924 TI - RNA polymerases from Pseudomonas aeruginosa and Pseudomonas syringae respond to Escherichia coli activator proteins. AB - The activities of RNA polymerases (RNAPs) from Pseudomonas aeruginosa and Pseudomonas syringae were compared with that of Escherichia coli RNAP. All three enzymes are able to initiate transcription at the trpBA promoter of P. aeruginosa and at the coliphage lambda promoters, pRM and pRE, in response to heterospecific activators (TrpI protein, repressor, and cII protein, respectively). However, both Pseudomonas polymerases have less stringent requirements for promoter recognition in the absence of activators than does E. coli RNAP. PMID- 1898925 TI - Catecholamine uptake, melanization, and oxygen toxicity in Cryptococcus neoformans. AB - Oxygen sensitivity mutations of Cryptococcus neoformans were mapped to three genetic loci. Three oxygen-sensitive mutants had mutations that appeared allelic and exhibited albinism tightly linked to oxygen sensitivity; these three and a fourth exhibited defects in catechol uptake and catechol oxidation to melanin. Catecholamine metabolism appears to protect C. neoformans from oxidants. PMID- 1898926 TI - Cloning and characterization of a pair of novel genes that regulate production of extracellular enzymes in Bacillus subtilis. AB - Two novel Bacillus subtilis genes that regulate the production of several extracellular enzymes were clones and characterized. These two genes are organized as part of an operon. When cloned in a multicopy plasmid, the first gene (tenA, transcription enhancement) stimulates alkaline protease production at the transcriptional level. The second gene (tenI) exerts an opposite effect to reduce alkaline protease production. The production of neutral protease, levansucrase, and alkaline protease can be stimulated up to 11- to 55-fold. Thus, tenA is a new member of the deg (regulatory genes for degradative enzymes) family in B. subtilis. A functional degS product is required to observe the stimulatory effect from tenA. Between the promoter and the ribosome-binding site of tenA, there exists a terminatorlike structure. Deletion of this structure doubles the expression of tenA. Neither tenA nor tenI is essential for cell growth and the production of extracellular enzymes. However, inactivation of these genes causes a delay in sporulation. This operon is located close to tre on the genetic linkage map. The overall organization of this operon and its relationship with other known regulatory factors in the deg family are discussed. PMID- 1898927 TI - Analysis of an mRNA exhibiting anomalous translational specificity. AB - Gene 6 mRNA of Bacillus subtilis phage phi 29 is inefficiently translated under standard in vitro conditions by Escherichia coli, while it is efficiently translated by the in vitro system derived from B. subtilis. This is a rare example of the inability of E. coli to translate mRNA translated by B. subtilis. The ionic condition in the translation systems was the key component in the differential recognition of the gene 6 message by E. coli and B. subtilis ribosomes. Its translation by E. coli ribosomes was preferentially inhibited by moderate levels of KCl, while its translation by B. subtilis ribosomes was unaffected by these concentrations of salt. This preferential inhibition with E. coli ribosomes was observed in vitro as well as in vivo. While not influencing the general phenomenon of preferential inhibition, anion-specific effects were observed in overall protein synthesis. Glutamate and acetate promoted efficient synthesis over a broad range of concentrations, whereas chloride was inhibitory at all concentrations tested. PMID- 1898928 TI - Identification and cloning of a fur regulatory gene in Yersinia pestis. AB - Yersinia pestis is one of many microorganisms responding to environmental iron concentrations by regulating the synthesis of proteins and an iron transport system(s). In a number of bacteria, expression of iron uptake systems and other virulence determinants is controlled by the Fur regulatory protein. DNA hybridization analysis revealed that both pigmented and nonpigmented cells of Y. pestis possess a DNA locus homologous to the Escherichia coli fur gene. Introduction of a Fur-regulated beta-galactosidase reporter gene into Y. pestis KIM resulted in iron-responsive beta-galactosidase activity, indicating that Y. pestis KIM expresses a functional Fur regulatory protein. A cloned 1.9-kb ClaI fragment of Y. pestis chromosomal DNA hybridized specifically to the fur gene of E. coli. The coding region of the E. coli fur gene hybridized to a 1.1-kb region at one end of the cloned Y. pestis fragment. The failure of this clone to complement an E. coli fur mutant suggests that the 1.9-kb clone does not contain a functional promoter. Subcloning of this fragment into an inducible expression vector restored Fur regulation in an E. coli fur mutant. In addition, a larger 4.8-kb Y. pestis clone containing the putative promoter region complemented the Fur- phenotype. These results suggest that Y. pestis possesses a functional Fur regulatory protein capable of interacting with the E. coli Fur system. In Y. pestis Fur may regulate the expression of iron transport systems and other virulence factors in response to iron limitation in the environment. Possible candidates for Fur regulation in Y. pestis include genes involved in ferric iron transport as well as hemin, heme/hemopexin, heme/albumin, ferritin, hemoglobin, and hemoglobin/haptoglobin utilization. PMID- 1898929 TI - Protein secretion in Pseudomonas aeruginosa: the xcpA gene encodes an integral inner membrane protein homologous to Klebsiella pneumoniae secretion function protein PulO. AB - xcp mutations have pleiotropic effects on the secretion of proteins in Pseudomonas aeruginosa PAO. The nucleotide sequence of a 1.2-kb DNA fragment that complements the xcp-1 mutation has been determined. Sequence analysis shows the xcpA gene product to be a 31.8-kDa polypeptide, with a highly hydrophobic character. This is consistent with a localization in the cytoplasmic membrane in P. aeruginosa, determined after specific expression of the xcpA gene under control of the T7 phi 10 promoter. A very strong homology was found between XcpA and PulO, a membrane protein required for pullulanase secretion in Klebsiella pneumoniae. This suggests the existence of a signal sequence-dependent secretion process common to these two unrelated gram-negative bacteria. PMID- 1898930 TI - Regulation of spo0H, a gene coding for the Bacillus subtilis sigma H factor. AB - The Bacillus spo0H gene codes for sigma H, which, as part of the RNA polymerase holoenzyme E sigma H, is responsible for the transcription of several genes which are expressed at the beginning of the sporulation process. In this communication, we examined the regulation of the spo0H gene of Bacillus subtilis by using lacZ reporter gene assays, quantitative RNA determinations, and Western immunoassay. The expression of the spo0H gene increases as the culture enters the mid logarithmic stage of growth. This increased expression requires the genes spo0A, spo0B, spo0E, and spo0F, and the requirement for at least spo0A and spo0B can be bypassed when the abrB gene is mutated. The expression of the spo0H gene is constitutive in the presence of the abrB mutation, being expressed at higher levels during vegetative growth. In addition, the sof-1 mutation, in the spo0A structural gene, can bypass the need for spo0F in spo0H expression. The transcriptional start site of spo0H was determined by using RNA made in vivo as well as in vitro. These studies indicate that spo0H is transcribed by the major vegetative RNA polymerase, E sigma A. spo0H RNA and sigma H levels during growth are not identical to each other or to the pattern of expression of spoVG, a gene transcribed by E sigma H. This suggests that spo0H is regulated posttranscriptionally and also that factors in addition to sigma H levels are involved in the expression of genes of the E sigma H regulon. PMID- 1898931 TI - The Bacillus subtilis sin gene, a regulator of alternate developmental processes, codes for a DNA-binding protein. AB - The sin gene of Bacillus subtilis encodes a dual-function regulatory protein, Sin, which is a negative as well as a positive regulator of alternate developmental processes that are induced at the end of vegetative growth in response to nutrient depletion. Sin has been purified to homogeneity by using a simple two-step procedure. It was found to bind to the developmentally regulated aprE (alkaline protease) gene at two sites in vitro. The stronger Sin-binding site (SBS-1) is located more than 200 bp upstream from the transcription start site. It is required for Sin repression of aprE expression in vivo, as strains bearing SBS-1 deletions were not affected by the sin gene. The second, weaker Sin binding site lies on a DNA fragment that contains the aprE promoter. Results of DNase I, exonuclease III, and dimethyl sulfate footprinting analysis of SBS-1 suggested that Sin binding involves two adjacent binding sites which appear to contain two different partial dyad symmetries. An analysis of the predicted amino acid sequence of Sin revealed a potential leucine zipper protein dimerization motif which is flanked by two helix-turn-helix motifs that could be involved in recognizing two different dyad symmetries. PMID- 1898932 TI - Nucleotide sequence and characterization of a Bacillus subtilis gene encoding a flagellar switch protein. AB - The nucleotide sequence of the Bacillus subtilis fliM gene has been determined. This gene encodes a 38-kDa protein that is homologous to the FliM flagellar switch proteins of Escherichia coli and Salmonella typhimurium. Expression of this gene in Che+ cells of E. coli and B. subtilis interferes with normal chemotaxis. The nature of the chemotaxis defect is dependent upon the host used. In B. subtilis, overproduction of FliM generates mostly nonmotile cells. Those cells that are motile switch less frequently. Expression of B. subtilis FliM in E. coli also generates nonmotile cells. However, those cells that are motile have a tumble bias. The B. subtilis fliM gene cannot complement an E. coli fliM mutant. A frameshift mutation was constructed in the fliM gene, and the mutation was transferred onto the B. subtilis chromosome. The mutant has a Fla- phenotype. This phenotype is consistent with the hypothesis that the FliM protein encodes a component of the flagellar switch in B. subtilis. Additional characterization of the fliM mutant suggests that the hag and mot loci are not expressed. These loci are regulated by the SigD form of RNA polymerase. We also did not observe any methyl-accepting chemotaxis proteins in an in vivo methylation experiment. The expression of these proteins is also dependent upon SigD. It is possible that a functional basal body-hook complex may be required for the expression of SigD regulated chemotaxis and motility genes. PMID- 1898933 TI - Positive regulation of the pts operon of Escherichia coli: genetic evidence for a signal transduction mechanism. AB - The pts operon of Escherichia coli is composed of the genes ptsH, ptsI, and crr, which code for three proteins of the phosphoenolpyruvate-dependent phosphotransferase system (PTS): the HPr, enzyme I (EI), and EIIIGlc proteins, respectively. These three genes are organized in a complex operon in which the major part of expression of the distal gene, crr, is initiated from a promoter region within ptsI. Expression from the promoter region of the ptsH and ptsI genes has been studied in vivo by using gene fusions with lacZ. Transcription from this promoter region is under the positive control of catabolite activator protein (CAP)-cyclic AMP (cAMP) and is also enhanced during growth in the presence of glucose (a PTS substrate). This report describes a genetic characterization of the mechanism by which growth on glucose causes transcriptional stimulation of the pts operon. This regulation is dependent on transport through the glucose-specific permease of the PTS, EIIGlc. Our results strongly suggest that transcriptional regulation of the pts operon is the consequence of an increase in the level of unphosphorylated EIIGlc which is produced during glucose transport. Furthermore, overproduction of EIIGlc in the absence of transport was found to stimulate expression of the pts operon. We also observed that CAP-cAMP could cause stimulation independently of the EIIGlc and that glucose could activate in the absence of cAMP in a strain overproducing EIIGlc. Our results indicate that glucose acts like an environmental signal through a mechanism of signal transduction. A sequence similarity between the C terminus of EIIGlc and the consensus of transmitter modules of the sensor proteins defined by E. C. Kofoid and J. S. Parkinson (Proc. Natl. Acad. Sci. USA 85:4981-4985, 1988) suggests that EIIGlc might have properties in common with the sensors of the two-component systems. PMID- 1898934 TI - Purification and characterization of acetoin:2,6-dichlorophenolindophenol oxidoreductase, dihydrolipoamide dehydrogenase, and dihydrolipoamide acetyltransferase of the Pelobacter carbinolicus acetoin dehydrogenase enzyme system. AB - Dihydrolipoamide dehydrogenase (DHLDH), dihydrolipoamide acetyltransferase (DHLTA), and acetoin: 2,6-dichlorophenolindophenol oxidoreductase (Ao:DCPIP OR) were purified from acetoin-grown cells of Pelobacter carbinolicus. DHLDH had a native Mr of 110,000, consisted of two identical subunits of Mr 54,000, and reacted only with NAD(H) as a coenzyme. The N-terminal amino acid sequence included the flavin adenine dinucleotide-binding site and exhibited a high degree of homology to other DHLDHs. DHLTA had a native Mr of greater than 500,000 and consisted of subunits identical in size (Mr 60,000). The enzyme was highly sensitive to proteolytic attack. During limited tryptic digestion, two major fragments of Mr 32,500 and 25,500 were formed. Ao:DCPIP OR consisted of two different subunits of Mr 37,500 and 38,500 and had a native Mr in the range of 143,000 to 177,000. In vitro in the presence of DCPIP, it catalyzed a thiamine pyrophosphate-dependent oxidative-hydrolytic cleavage of acetoin, methylacetoin, and diacetyl. The combination of purified Ao:DCPIP OR, DHLTA, and DHLDH in the presence of thiamine pyrophosphate and the substrate acetoin or methylacetoin resulted in a coenzyme A-dependent reduction of NAD. In the strictly anaerobic acetoin-utilizing bacteria P. carbinolicus, Pelobacter venetianus, Pelobacter acetylenicus, Pelobacter propionicus, Acetobacterium carbinolicum, and Clostridium magnum, the enzymes Ao:DCPIP OR, DHLTA, and DHLDH were induced during growth on acetoin, whereas they were absent or scarcely present in cells grown on a nonacetoinogenic substrate. PMID- 1898936 TI - Twisted arms and ethical choices. PMID- 1898935 TI - Conservation of the gene for outer membrane protein OprF in the family Pseudomonadaceae: sequence of the Pseudomonas syringae oprF gene. AB - The conservation of the oprF gene for the major outer membrane protein OprF was determined by restriction mapping and Southern blot hybridization with the Pseudomonas aeruginosa oprF gene as a probe. The restriction map was highly conserved among 16 of the 17 serotype strains and 42 clinical isolates of P. aeruginosa. Only the serotype 12 isolate and one clinical isolate showed small differences in restriction pattern. Southern probing of PstI chromosomal digests of 14 species from the family Pseudomonadaceae revealed that only the nine members of rRNA homology group I hybridized with the oprF gene. To reveal the actual extent of homology, the oprF gene and its product were characterized in Pseudomonas syringae. Nine strains of P. syringae from seven different pathovars hybridized with the P. aeruginosa gene to produce five different but related restriction maps. All produced an OprF protein in their outer membranes with the same apparent molecular weight as that of P.aeruginosa OprF. In each case the protein reacted with monoclonal antibody MA4-10 and was similarly heat and 2 mercaptoethanol modifiable. The purified OprF protein of the type strain P. syringae pv. syringae ATCC 19310 reconstituted small channels in lipid bilayer membranes. The oprF gene from this latter strain was cloned and sequenced. Despite the low level of DNA hybridization between P. aeruginosa and P. syringae DNA, the OprF gene was highly conserved between the species with 72% DNA sequence identity and 68% amino acid sequence identity overall. The carboxy terminus encoding region of P. syringae oprF showed 85 and 33% identity, respectively, with the same regions of the P. aeruginosa oprF and Escherichia coli ompA genes. PMID- 1898937 TI - Hyperparathyroidism, estrogens, and osteoporosis. PMID- 1898938 TI - The litmus test. PMID- 1898939 TI - Champion of the helpless in our midst. PMID- 1898940 TI - Raynaud's disease: an update. AB - This often painful disease may be primary or secondary. Simple preventive measures sometimes provide symptomatic control. When such efforts fail, the most effective agents available are calcium channel blockers. PMID- 1898941 TI - Caribbean traveler with diarrhea and abdominal distention. PMID- 1898942 TI - A young woman with syncope and an abnormal ECG. PMID- 1898943 TI - To circumcise or not. AB - The link to urinary tract infection during infancy has renewed the neonatal circumcision debate, with all of its emotional overtones. Proponents maintain that the intact prepuce invites bacterial colonization, and this in turn can lead to permanent renal damage. Opponents cite disadvantages and risks of the procedure. An effort is made to separate facts from assumptions. PMID- 1898944 TI - A 'classic case of Crohn's disease'. PMID- 1898945 TI - Cases that teach clinical reasoning. PMID- 1898946 TI - Of dead brains, living wills, and autonomy. AB - Recent court decisions have clarified many important bioethical and medicolegal issues. Brain death, living wills, and patient autonomy are being defined by the rulings. PMID- 1898947 TI - A 7-year-old girl with pubic hair: premature adrenarche or not? PMID- 1898948 TI - Mediators of meningitis: therapeutic implications. AB - Despite the availability of potent antibiotics, bacterial meningitis is still a major clinical problem. Mortality is high, and up to a third of survivors are left with neurologic sequelae that may range from mild behavioral disorders to mental retardation or deafness. New therapeutic approaches to meningeal inflammation, however, are reducing the neurologic risks. PMID- 1898949 TI - Antibiotic-resistant pneumonia in a hemophiliac with AIDS. PMID- 1898950 TI - The pulmonary surfactant system. AB - Surfactant's importance is underscored by the severe morbidity of deficiency states--primary, as in neonatal respiratory distress syndrome, or secondary, as in ARDS. Current knowledge of surfactant synthesis and metabolism is reviewed. Clinically, the effectiveness of exogenous surfactant in RDS has prompted investigation of its administration in ARDS. PMID- 1898951 TI - Reasons for the lack of benefit of immediate angioplasty during recombinant tissue plasminogen activator therapy for acute myocardial infarction: a regional wall motion analysis. European Cooperative Study Group. AB - Regional ventricular wall motion analysis utilizing three different methods was performed on predischarge left ventriculograms from 291 of 367 patients enrolled in a randomized trial of single chain recombinant tissue-type plasminogen activator (rt-PA), aspirin and heparin with and without immediate angioplasty in patients with acute myocardial infarction. With univariate analysis, no difference in regional wall motion variables between the two treatment groups was observed. However, with individual baseline risk assessment by multivariate linear regression analysis using baseline characteristics known to be related to left ventricular function after thrombolytic therapy or outcome of coronary angioplasty, or both, an excess of high risk patients in the invasive treatment group was detected. To adjust for this unequal distribution of baseline risk, multivariate linear regression analysis was performed. No benefit of immediate coronary angioplasty was observed after adjustment. Reocclusion or reinfarction, or both, occurred more frequently in the invasive than in the noninvasive treatment group (18% versus 13%, respectively). Among patients with a patent infarct-related vessel on angiography between days 10 and 22 and without reinfarction before angiography, there was a trend toward benefit from the invasive strategy, indicating that reocclusion and reinfarction might be responsible for the lack of benefit of the invasive strategy. This implies that immediate coronary angioplasty may be beneficial in selected patients, provided that these complications can be prevented. PMID- 1898952 TI - Cardiac tamponade early after thrombolysis for acute myocardial infarction: a rare but not reported hemorrhagic complication. AB - Among 392 consecutive patients admitted for acute myocardial infarction and treated with thrombolytic drugs, 4 patients (1%) developed an early hemorrhagic pericardial effusion (without ventricular wall rupture) evolving within 24 h to cardiogenic shock consequent to cardiac tamponade. They all suffered from a large anterior myocardial infarction treated within 4 h after onset of symptoms with intravenous anisoylated plasminogen streptokinase activator complex (one case), recombinant tissue-type plasminogen activator (rt-PA) (two cases) or streptokinase (one case), anticoagulation with heparin (all cases) and aspirin (three cases). As soon as pericardial effusion was established by echocardiography, emergency percutaneous pericardiocentesis was performed at the bedside 20 +/- 6 h after thrombolytic therapy was started. This corrected immediately the clinical and hemodynamic status of each patient and a catheter was left in the pericardial space for 34 +/- 18 h. Thus, in the presence of unexplained clinical and hemodynamic deterioration occurring during the first 24 h after thrombolytic treatment of a large myocardial infarction, cardiac tamponade should be suspected. Immediate percutaneous pericardiocentesis followed by continuous drainage is a simple and definitive treatment for this complication. PMID- 1898953 TI - International comparison of long-term care: the need for resident-level classification. AB - Differences between long-term care facilities in Stockholm (1134 residents) and New York (95,000 residents statewide) were examined. The comparison employed a resident classification system, Resource Utilization Groups (RUG-II), which links individuals' characteristics to resource use. Distributions of Activity of Daily Living functionality and RUG-II categories demonstrated significant differences between these two populations, with the Stockholm facilities more akin to the heavier care skilled nursing facilities in New York. These differences may indicate different uses of long-term care beds in the United States and Sweden and demonstrate the need for resident-level classification systems in cross national studies. PMID- 1898954 TI - Urodynamics. PMID- 1898955 TI - Delayed plasma clearance of phenylalanine and tyrosine in elderly men. AB - The plasma levels of 17 amino acids were measured in three groups of men: healthy young men, healthy elderly men, and demented tube-fed elderly men living in a nursing home, prior to, and again 2, 4, and 6 hours after the consumption of a standard protein-containing meal. The standard meal provided per kilogram of body weight 8.3 calories, 0.33 grams of protein, 0.90 grams of carbohydrate, and 0.37 grams of fat. The concentrations of all amino acids, except tryptophan, rose significantly at 2 hours and returned to baseline by 6 hours. Plasma phenylalanine and tyrosine were significantly (P less than 0.05) higher at 2 hours in the two groups of elderly men than in the young healthy men. In other respects the pre- and post-prandial amino acid profiles were not influenced by age. The ratio, tyrosine/other large neutral amino acids (tyr/LNAA), was significantly higher in both elderly groups than in the young men at nearly all time points before and after the test meal. It was generally higher in the demented older men than in the healthy older men. The data demonstrated a delayed plasma clearance of phenylalanine and tyrosine in old age. The elevated plasma tyr/LNAA ratio in the elderly men may have tended to augment an entry of tyrosine, the precursor of norepinephrine and dopamine, into their brains. PMID- 1898956 TI - Chronobiology and aging. PMID- 1898957 TI - Clinical fallout from the Supreme Court decision on Nancy Cruzan: Chernobyl or Three Mile Island? PMID- 1898958 TI - Human B cells secrete predominantly lambda L chains in the absence of H chain expression. AB - Ig H and L chains are independently assembled in B cells and then secreted together as a functional protein. H chains cannot be secreted without assembly to L chains; however, L chains can be secreted in the absence of H chains by both mice and human cells. To examine the influence of H chain expression on human L chain isotype selection (kappa or lambda), we compared the kappa/lambda ratio of L chains unassociated with H chains (free L chains) to the kappa/lambda ratio of L chains associated with H chains. Culture supernatants of human splenocytes were assayed for kappa and lambda L chains. Free L chains were the predominant form of L chains detected in unstimulated cultures, accounting for 68 to 70% of the total. This was in contrast to the minor proportion that free L chains represented (less than 20%) in cultures stimulated with PWM or LPS (p less than 0.01). Furthermore, the kappa/lambda ratio of light chains detected in unstimulated cultures was 0.5 as compared to 1.3 for PWM stimulated cultures (p = 0.0001). To demonstrate that the decreased kappa/lambda ratio of L chains in the supernatants of cultures of unstimulated B cells was due to free L chains, we measured the kappa/lambda ratio of IgG and IgM-associated L chains. In both the stimulated and unstimulated cultures, the kappa/lambda ratio of L chains associated with H chains was greater than the ratio determined for free L chains. Free L chains were shown to be predominantly lambda as compared to the predominantly kappa phenotype of L chains associated with H chains. Thus absence of H chain expression affects selection of L chain isotypes secreted by human B cells. PMID- 1898959 TI - The specificity properties that distinguish members of a set of homologous anti digoxin antibodies are controlled by H chain mutations. AB - Five murine A/J strain anti-digoxin mAb (35-20, 40-40, 40-120, 40-140, and 40 160) have highly homologous H and L chain V regions, only differing by somatic mutation, yet differ in affinity and specificity. The availability of the VH and VL genomic clones from one hybridoma, 40-140, has now allowed studies involving in vitro mutagenesis and chain recombination among these five hybridomas. To determine the relative contributions of the mutations found in either VH or VL to the overall binding properties of these antibodies, we recombined the 40-140VH with the VL of each hybridoma. The 40-140VH gene was transfected into hybridoma variants that produce only VL. The recombinant antibodies show that the mutations present in VH, rather than in VL, affect the fine specificity properties of these antibodies, whereas, the mutations among both VH and VL chains are important in determining antigen affinity. From mutations present in VH that affect fine specificity properties, the comparison of the antibody sequences, and from the previously measured binding properties, we predicted and tested selected VH mutations for their ability to alter specificity or affinity by doing site directed in vitro mutagenesis. The results for the somatic mutations found in this group of antibodies show: 1) VH mutations control the fine specificity properties that distinguish different members of this group; 2) in particular, VH residues 54 and 55 in CDR2 control the distinguishing characteristics of specificities between these antibodies; and 3) by mutagenesis, we had the unusual result of being able to alter Ag specificity without affecting affinity. A computer model of the 40-140 antibody binding site was generated which indicates that VH residues 54 and 55 are highly accessible. PMID- 1898960 TI - The sequential generation of neutrophil chemoattractant proteins in acute inflammation in the rabbit in vivo. Relationship between C5a and proteins with the characteristics of IL-8/neutrophil-activating protein 1. AB - An in vivo experimental peritonitis model was investigated in the rabbit using zymosan as the inflammatory stimulus. After an i.p. injection of zymosan, exudate was removed at intervals and tested in the back skin of assay rabbits. Assay rabbits received i.v. injections of 125I-albumin and 111In-neutrophils, and the local accumulation of each label was measured in response to intradermal injections of exudate samples mixed with a potentiating dose of PGE2. When peritoneal exudate samples were tested in the presence of a specific anti-C5a antibody, virtually all the edema-inducing and neutrophil chemoattractant activity was abolished in samples taken up to 2 h after the zymosan injection. Later samples, however, contained increasing levels of a non-C5a component. In C5a-depleted 6-h exudate two peaks of inflammatory activity were separated using cation exchange HPLC. Evidence is presented that C5a itself is unable to stimulate the production of these activities. Both peaks of activity appear related to IL-8/NAP-1 as they inhibited the binding of 125I-IL-8/NAP-1 to human neutrophils. PMID- 1898962 TI - The role of T lymphocytes in immunity to Plasmodium falciparum. Enhancement of neutrophil-mediated parasite killing by lymphotoxin and IFN-gamma: comparisons with tumor necrosis factor effects. AB - Human neutrophils were treated with IFN-gamma or lymphotoxin and their interaction with the asexual blood forms of Plasmodium falciparum was studied by a radiometric assay and microscopy. The results showed that human neutrophils inhibited the growth of P. falciparum and killed the parasite via a phagocytic mechanism. The cytokines significantly augmented the neutrophil-mediated killing of the parasite. When compared with the effects of TNF-alpha similar results were seen although IFN-gamma and TNF-alpha were effective at 10-fold less the concentration of lymphotoxin. The maximum neutrophil-mediated parasite killing was seen in the presence of immune serum and the cytokines. These findings suggest that T cells regulate the antimalarial activity of neutrophils. PMID- 1898961 TI - Modulation of monocyte chemotactic function in inflammatory lesions. Role of inflammatory mediators. AB - Monocyte recruitment and accumulation in the synovial tissue is pivotal in the evolution of rheumatoid arthritis (RA). In the present study we examined the chemotactic potential of monocytes obtained from synovial fluid (SF) of patients with RA. Functionally, SF monocytes exhibited greatly diminished chemotactic activity to C5a compared with monocytes from the peripheral blood. In contrast, their chemotactic responsiveness to the synthetic peptide, FMLP, was nearly normal. To define a mechanism for this differential chemotactic dysfunction, cell surface receptors for C5a (C5aR) and FMLP (FMLP-R) were evaluated. Whereas FMLP-R expression was similar on both blood and inflammatory monocytes, C5aR expression was markedly reduced on SF cells. Because decreased C5a binding in certain RA SF samples could not be attributed to free C5a, known or suspected components of inflammatory SF were evaluated for their ability to modulate chemotactic ligand receptors. Bacterial products including LPS and streptococcal cell walls, which are potent monocyte activators, down-regulated C5aR without affecting FMLP-R. Moreover, the cytokines IFN-gamma and granulocyte-macrophage-CSF selectively decreased C5aR in parallel with decreased in vitro chemotactic activity to C5a. Thus, these data indicate that 1) synovial effusions may contain C5a and/or inflammatory mediators that modulate phenotypic and functional changes in monocytes, 2) chemotactic ligand receptors are independently regulated in inflammatory lesions, and 3) decreased C5aR expression and chemotactic potential likely provide a mechanism whereby monocyte-macrophages persist within the inflamed synovium. PMID- 1898963 TI - Agonist/inositol trisphosphate-induced release of calcium from murine keratinocytes: a possible link with keratinocyte differentiation. AB - Extracellular calcium concentrations markedly affect the pattern of proliferation and differentiation in cultured keratinocytes. When medium contains 0.1 mM calcium or above, the cells lose their proliferative ability, rapidly stratify, and terminally differentiate. Because 1,25(OH)2D3 (a modulator of Ca++ homeostasis) enhances the differentiation of keratinocytes, we investigated whether a link exists between 1,25(OH)2D3-induced release of inositol-1,4,5 trisphosphate (Ins(1,4,5)P3) from PtdIns 4,5-P2 and intracellular calcium [Ca++]i release from keratinocytes. Specifically, primary culture of keratinocytes were loaded with fluorescence dye Fura-2AM (10 microM) and changes in fluorescence intensity were monitored at the excitation wavelengths of 340 and 380 nm and emission wavelength of 505 nm. Additions of two agonists, 1,25(OH)2D3 (1.2 x 10( 9) M) and 13-Cis retinoic acid (0.2 x 10(-9) M), to dye-loaded keratinocytes induced rapid release of [Ca++]i, respectively, followed by gradual return to the prestimulated state. Addition of Ins(1,4,5)P3 (10 microM) to saponin-treated (leaky) keratinocytes also resulted in a rapid release of [Ca++]i. In contrast, the addition of inositol-1,3,4,5-tetrakisphosphate Ins(1,3,4,5)P4 at similar concentrations exerted negligible effect. Taken together, these results support the view that 1,25(OH)2D3-induced [Ca++]i release in keratinocytes may be via the Ins(1,4,5)P3-induced early release of intracellular [Ca++]i. This may explain, at least in part, 1,25(OH)2D3-enhanced keratinocyte differentiation. PMID- 1898964 TI - Physiologic distribution and differentiation of melanocytes in human fetal and neonatal skin equivalents. AB - There is evidence that epidermal keratinocytes play a critical role in melanocyte position and differentiation in the epidermis, although little is known about the molecular mechanisms involved. We have used an in vitro skin equivalent as a model system in which to study keratinocyte/melanocyte interactions in both fetal and neonatal skin. Because the skin equivalent model has been shown to closely simulate the morphologic and biochemical features of differentiated epidermis we hypothesized that the factors that influence melanocyte position and differnetiation would also function in this system. Localization of melanocytes in skin equivalents, using the monoclonal antibody HMB-45, established that melanocytes in fetal skin equivalents are grouped and distributed both basally and suprabasally, whereas melanocytes in neonatal skin equivalents are singly distributed among basal epidermal keratinocytes, similar to the distributions of fetal and neonatal melanocytes, respectively, in vivo. Similarly, in fetal and neonatal skin equivalents the patterns of expression of a number of melanoma/melanocyte-associated antigens closely parallels that seen in vivo. These results suggest that the skin equivalent model is an excellent system in which to study the dynamic factors that regulate melanocyte migration, proliferation, and differentiation during ontogeny and post-natal differentiation of the skin. PMID- 1898965 TI - Caffeine-sensitive calcium stores in bovine adrenal chromaffin cells. AB - Caffeine was used to study the intracellular Ca2+ pools of bovine chromaffin cells. Its effects on cytosolic Ca2+ concentration ([Ca2+]i) were examined using fura-2. Caffeine caused a transient increase in [Ca2+]i in the presence or absence of extracellular Ca2+. In the former case, the caffeine-induced [Ca2+]i increase was higher and stayed above the basal value for several minutes. In the latter case, the [Ca2+]i rise was lower and fell to the basal level within 1 min. These results suggest that caffeine increases [Ca2+]i by causing both Ca2+ influx and Ca2+ release from intracellular pools. In the absence of extracellular Ca2+, ionomycin but not caffeine caused a further increase in [Ca2+]i in cells that had been treated with caffeine. Apparently there are at least two intracellular Ca2+ pools, only one of which is sensitive to caffeine. The caffeine-induced [Ca2+]i rise became smaller when the cells were pretreated with the inositol trisphosphate-generating agonists, methacholine and bradykinin. In addition, methacholine was unable to initiate a [Ca2+]i transient after the cells had been treated with caffeine. The results indicate that the caffeine-sensitive Ca2+ pools overlap with the inositol trisphosphate-sensitive pool and that the size of the latter pool is smaller than that of the former. The caffeine-sensitive Ca2+ pools were refilled after high K+ treatment, which suggests that the caffeine sensitive Ca2+ pools may be important in buffering the cytosolic Ca2+. The effect of caffeine on [Ca2+]i is not due to inhibition of phosphodiesterase. Our results support a Ca2+ entry model in which depletion of intracellular Ca2+ pools controls the rate of Ca2+ entry across the plasma membrane. PMID- 1898966 TI - Effect of precursor loading on the synthesis rate and release of dopamine and serotonin in the striatum: a microdialysis study in conscious rats. AB - The effects of systemic administration of tyrosine and phenylalanine on the extracellular levels of tyrosine and dopamine were determined by microdialysis in the striatum of awake rats. In addition, the effects of these precursors on in vivo 3,4-dihydroxyphenylalanine (DOPA) formation were determined during continuous infusion of a decarboxylase inhibitor. Both precursors increased the dialysate levels of tyrosine sixfold, but only phenylalanine administration stimulated DOPA formation. However, neither precursor affected the release of dopamine. When the precursor administration was repeated in rats in which the release of dopamine was stimulated by haloperidol pretreatment, again no effect was seen on the release of dopamine. Systemic administration of tryptophan (100 mg/kg, i.p.) during continuous infusion of a decarboxylase inhibitor induced a threefold increase in the formation of 5-hydroxytryptophan and caused an increase in the release of serotonin during infusion of an uptake inhibitor to about 150% of controls. Finally, we investigated whether dietary precursors were able to influence neurotransmitter formation and release. Rats trained to consume their daily food in a period of 2 h were implanted with microdialysis probes. Scheduled eating induced a small increase in the extracellular levels of tyrosine (135% of controls), but the release of dopamine and the formation of 5-hydroxytryptophan during continuous infusion of a decarboxylase inhibitor were not affected. PMID- 1898967 TI - Chronic electroconvulsive treatment augments coupling of the GTP-binding protein Gs to the catalytic moiety of adenylyl cyclase in a manner similar to that seen with chronic antidepressant drugs. AB - A significant increase of guanylylimidodiphosphate (GppNHp)-, fluoride-, and forskolin-stimulated adenylyl cyclase was observed in synaptic membrane preparations from rat cerebral cortex subsequent to chronic electroconvulsive shock (ECS) treatment. This effect required at least five treatments over a course of 10 days. The inhibition of adenylyl cyclase induced by GppNHp was not affected by these treatments. The dissociation constant (KD) and maximal binding for the photoaffinity GTP analog, [32P]P3-(4-azidoanilido)-P1-5'-GTP [( 32P]AAGTP), to each of the synaptic membrane G proteins also were unchanged after ECS treatment. Nonetheless, the transfer of [32P]AAGTP from Gi to Gs, which we suggest is indicative of the coupling between Gs and the adenylyl cyclase catalytic moiety, was accelerated by chronic ECS treatment but not by acute or sham treatment. Furthermore, chemical uncoupling of Gs from adenylyl cyclase rendered membranes from treated animals indistinguishable from controls. Finally, in all cases tested, membranes prepared from animals subjected to chronic treatment with amitriptyline or iprindole showed similar changes in the Gs mediated activation of adenylyl cyclase. Acute treatments produced effects similar to controls, and liver and kidney membranes from animals receiving chronic treatment showed no changes in adenylyl cyclase despite the marked changes seen in brain. These results suggest that chronic administration of ECS enhances coupling between Gs and adenylyl cyclase enzyme and modifies interactions between Gs and Gi. PMID- 1898968 TI - Sodium fluoride mimics the effect of prostaglandin E2 on catecholamine release from bovine adrenal chromaffin cells. AB - We have reported recently that prostaglandin E2 (PGE2) stimulated phosphoinositide metabolism in bovine adrenal chromaffin cells and that PGE2 and ouabain, an inhibitor of Na+, K(+)-ATPase, synergistically induced a gradual secretion of catecholamines from the cells. Here we examined the involvement of a GTP-binding protein(s) in PGE receptor-induced responses by using NaF. In the presence of Ca2+ in the medium, NaF stimulated the formation of all three inositol phosphates, i.e., inositol monophosphate, bisphosphate, and trisphosphate, linearly over 30 min in a dose-dependent manner (15-30 mM). This effect on phosphoinositide metabolism was accompanied by an increase in cytosolic free Ca2+. NaF also induced catecholamine release from chromaffin cells, and the dependency of stimulation of the release on NaF concentration was well correlated with those of NaF-enhanced inositol phosphate formation and increase in cytosolic free Ca2+. Although the effect of NaF on PGE2-induced catecholamine release in the presence of ouabain was additive at concentrations below 20 mM, there was no additive effect at 25 mM NaF. Furthermore, the time course of catecholamine release stimulated by 20 mM NaF in the presence of ouabain was quite similar to that by 1 microM PGE2, and both stimulations were markedly inhibited by amiloride, with half-maximal inhibition at 10 microM. Pretreatment of the cells with pertussis toxin did not prevent, but rather enhanced, PGE2-induced catecholamine release over the range of concentrations examined. These results demonstrate that NaF mimics the effect of PGE2 on catecholamine release from chromaffin cells and suggest that PGE2-evoked catecholamine release may be mediated by the stimulation of phosphoinositide metabolism through a putative GTP binding protein insensitive to pertussis toxin. PMID- 1898969 TI - Contribution of antibody response to recombinant HIV-1 gene-encoded products nef, rev, tat, and protease in predicting development of AIDS in HIV-1-infected individuals. AB - The relation between antibody-response profiles to Escherichia coli-produced HIV 1 nef, rev, tat, and protease proteins and the risk of developing AIDS was studied using stored serum samples taken sequentially from a cohort of 195 initially symptom-free men who were seropositive for antibodies to HIV-1 structural proteins and 72 men who seroconverted for such antibodies. The AIDS attack rates at 39 months follow-up were significantly higher in the men with negative versus positive antibody profiles to nef, tat, and protease, respectively. [Difference (D) between attack rates = 11.279, 5.884, and 8.322, respectively]. No significant difference was found between men with negative versus positive antibody profiles to rev. The above differences between AIDS attack rates were clearly lower than those reported from the same cohort for men who were serum HIV-1 antigen positive versus negative, and for men with low versus normal CD4+ lymphocyte counts, but with respect to nef antibody-response profiles, resembled the difference reported between anti-HIV-1 core antibody negative versus antibody-positive men. In the subgroup of men without any of the markers previously found to be predictive of progression to AIDS in the cohort (persistent HIV-1 p24 antigenemia, low anti-HIV-1 anti-core antibody reactivity, and low CD4+ cell counts), antibody profiles to nef, rev, tat, and protease did not contribute to the prediction of outcome of infection. When used in combination with persistent HIV-1 p24 antigenemia and low CD4+ cell counts, negative antibody profiles to nef and protease, respectively, were equally sensitive and specific in predicting progression to AIDS, as was low anti-HIV-1 anti-core antibody reactivity. PMID- 1898970 TI - Immunogenic peptides of influenza virus subtype N1 neuraminidase identify a T cell determinant used in class II major histocompatibility complex-restricted responses to infectious virus. AB - Six nonoverlapping peptides of the neuraminidase (NA) glycoprotein of influenza virus A/Puerto Rico/8/34 (H1N1) (PR8 virus) were found to be immunogenic for proliferating T cells when injected into BALB/c mice in Freund adjuvant. T cells elicited by peptide immunization could recognize PR8 virus in vitro. However, only one of these peptides, corresponding to residues 79 to 93 of NA (NA 79-93), was able to restimulate T cells of mice immunized with infectious virus. T cells that recognized this peptide were uniformly I-Ed restricted, yet infectious influenza virus was required for responses. NA 79-93-specific T-hybridoma clones raised by immunization either with whole virus or with the synthetic peptide alone each responded to replicative virus and not to UV-inactivated virions. These data suggest that the NA 79-93 T-cell determinant which is commonly presented during an encounter with influenza virus in vivo is processed preferentially from NA synthesized within antigen-presenting cells. PMID- 1898971 TI - Solid matrix-antibody-antigen complexes induce antigen-specific CD8+ cells that clear a persistent paramyxovirus infection. AB - We have previously shown that the adoptive transfer of splenocytes, isolated from mice immunized by infection with the paramyxovirus simian virus 5 (SV5), enhance the speed of clearance of SV5 from the lungs of immunodeficient mice; clearance is mediated primarily through CD8+ effector cells and not by serum neutralizing antibody (D.F. Young, R.E. Randall, J.A. Hoyle, and B.E. Souberbielle, J. Virol. 64:5403-5411, 1990). In this article we demonstrate that immunization of mice with solid matrix-antibody-antigen (SMAA) complexes also induces CD8+ effector cells that are responsible for clearing persistent SV5 infections in immunodeficient mice. The demonstration that immunization with SMAA complexes (an exogenous antigen) can induce class I-restricted cytotoxic T lymphocytes (CTLs) suggests that that these cells may be responsible for virus clearance in vivo. This premise is supported indirectly by the observation that immunization with SMAA complexes was less efficient in inducing class I-restricted CTLs (as measured in vitro) than was infectious virus and that splenocytes isolated from mice immunized with SMAA complexes were also less efficient in clearing virus from lungs of immunodeficient mice than were splenocytes isolated from mice immunized by infection with virus. This was not because the SMAA complexes were generally less immunogenic than infectious virus, since mice immunized with SMAA complexes (which contained the HN protein of SV5) produced higher levels of neutralizing antibody than mice immunized with infectious virus. In the majority of experiments, fixed and killed suspensions of Staphylococcus aureus Cowan strain A were used as the solid matrix in the construction of SMAA complexes. However, in this article we present evidence that alum-antibody-antigen complexes are as immunogenic as S. aureus A-antibody-antigen complexes. These results suggest that the immunological reactivity of the solid matrix itself does not influence the intensity of the immune response to the antigens of interest in the SMAA complexes. The significance of these results for vaccine design are discussed. PMID- 1898972 TI - Differential loss of envelope glycoprotein gp120 from virions of human immunodeficiency virus type 1 isolates: effects on infectivity and neutralization. AB - Several parameters which may affect the infectivity of human immunodeficiency virus type 1 in tissue culture were analyzed. In particular, we used gel exclusion chromatography to investigate how the loss of the surface glycoprotein gp120 from virions of the HTLV-IIIB (IIIB), HTLV-IIIRF (RF), and SF-2 isolates modulates infectivity. In IIIB and RF cultures, a high proportion of the total gp120 was virion bound initially but was gradually lost from the virions over time. In contrast, most of the gp120 (and p24) in SF-2-infected cultures was soluble and the few particles present had a fivefold-lower level of virus-bound gp120. However, this reduced level of virion-bound gp120 was more resistant to shedding. Loss of a major proportion of gp120 from IIIB and RF virions resulted in reduced infectivities, and in addition, the resulting accumulation of soluble gp120 in the cultures could competitively inhibit viral infection, especially with SF-2. Increased shedding of virion gp120 also affected the neutralization of IIIB and RF particles. However, the high sensitivity to human serum neutralization characteristic of SF-2 was unaffected by soluble gp120 in cultures, suggesting that the epitopes responsible are not present on soluble gp120. PMID- 1898973 TI - Genetic characterization of the vaccinia virus DNA polymerase: identification of point mutations conferring altered drug sensitivities and reduced fidelity. AB - We determined that 85 microM aphidicolin was sufficient to block macroscopic plaque formation by vaccinia virus and to cause a 10(4)-fold reduction in viral yield from a wild-type infection. A chemically mutagenized viral stock was passaged sequentially in the presence of drug, and plaque-purified viral stocks resistant to aphidicolin were isolated and characterized. By use of a marker rescue protocol, the lesion in each mutant was found to map within the same 500 bp fragment within the DNA polymerase gene. All of the mutants were found to contain a single nucleotide change in the same codon. In nine of these mutants, the alanine residue at position 498 was changed to a threonine, whereas a 10th mutant sustained a valine substitution at this position. Congenic viral strains which carried the Aphr lesion in an unmutagenized wild-type background were isolated. The Thr and Val mutations were found to confer equivalent levels of drug resistance. In the presence of drug, viral yields were 25% of control levels, and the levels of viral DNA synthesized were 30 to 50% of those seen in control infections. The two mutations also conferred an equivalent hypersensitivity to the cytosine analog 1-beta-D-arabinofuranosylcytosine (araC); strains carrying the Thr mutation were moderately hypersensitive to the pyrophosphate analog phosphonoacetic acid and the adenosine analog araA, whereas the Val mutation conferred acute hypersensitivity to these inhibitors. The Val mutation also conferred a mutator phenotype, leading to a 20- to 40-fold increase in the frequency of spontaneous mutations within the viral stock. PMID- 1898975 TI - Posttranscriptional regulation of interferon mRNA levels in peritoneal macrophages. AB - Low levels of beta interferon (IFN) mRNA are transcribed in freshly explanted murine peritoneal macrophages. Nuclear runoff transcription assays show that this "constitutive" IFN-beta-mRNA transcription does not increase in macrophages treated either with lipopolysaccharide or with IFN-gamma, which induce a marked accumulation of this mRNA and greatly increase IFN secretion. Therefore, these agents promote accumulation of IFN-beta mRNA by posttranscriptional mechanisms. The IFN-alpha 2 gene is also constitutively transcribed by macrophages, but the corresponding mRNA does not accumulate in lipopolysaccharide-treated cells. PMID- 1898974 TI - Evidence for neurotoxic activity of tat from human immunodeficiency virus type 1. AB - The human immunodeficiency virus (HIV) genome codes for a trans-activating regulatory protein, tat. Using chemically synthesized tat, it was found that 125I tat and 125I-tat38-86 specifically bound to rat brain synaptosomal membranes with moderate affinity (K0.5 = 3 microM). Interaction of tat with nerve cells was also revealed by flow cytometry, which showed its binding to rat glioma and murine neuroblastoma cells, using both direct fluorescence with fluorescein isothiocyanate-labeled tat and indirect immunofluorescence assays. This interaction was investigated with electrophysiology using isolated excitable frog muscle fibers and cockroach giant interneuron synapses. tat acted on the cell membrane and induced a large depolarization, accompanied by a decrease in membrane resistance, thereby modifying cell permeability. The neurotoxicity of tat was further demonstrated in vitro, on glioma and neuroblastoma cell growth, as well as by a 51Cr release assay in both tumor cell lines. Interestingly, no hemolytic activity of tat for human erythrocytes was found even when tat was tested at its highly neurotoxic concentration. Experiments in vivo showed that synthetic tat is a potent and lethal neurotoxic agent in mice. The use of tat peptide derivatives showed that basic region from 49 to 57 is necessary and sufficient for binding to cell membranes and toxicity. PMID- 1898976 TI - The cost-effectiveness of misoprostol. PMID- 1898977 TI - Effects of intraperitoneal chemotherapy on anastomotic healing in the rat. AB - The effect of perioperative intraperitoneal (ip) (2 mg/kg) vs intravenous (iv) (1.5 mg/kg) mitomycin-C on healing of intestinal anastomoses was studied in rats after jejunal section and anastomosis. When the animals were killed 7 days after surgery 52.8% in the ip group had an anastomotic leak (41.2% causing death of the animals), compared to 20% in the iv group and none in the control group. Mean anastomotic bursting pressure was 156 mm Hg in the ip group, 178 mm Hg in the iv group, and 203 mm Hg in controls (P less than 0.01). Hydroxyproline content of the intestinal segment containing the anastomosis was 2.26 micrograms/mg in the ip group, 3.49 in the iv, and 4.91 in controls (ip vs controls, P less than 0.01). Histological examination of the anastomoses in rats given ip mitomycin showed significantly "slower" anastomotic healing than in iv rats and controls. Electron microscopy showed that the mean diameter of collagen fibers was significantly smaller (P less than 0.05) in ip rats (34 nm) than iv (51 nm) and controls (79 nm). An intraoperative bolus of mitomycin thus significantly impaired the healing of a jejunal anastomosis in the rat, more so after ip than iv injection. Thus in clinical practice ip adjuvant chemotherapy after surgery should perhaps be delayed until wound repair has reached an advanced stage. PMID- 1898978 TI - Trichinella spiralis infection--United States, 1990. AB - Since 1947, when the Public Health Service began to record statistics on trichinosis, the number of cases reported by state health departments each year has declined: in the late 1940s, health departments reported an average of 400 cases and 10-15 deaths each year; from 1982 through 1986, the number declined to an average of 57 per year (Figure 1) and a total of three deaths (1,2). Although this trend reflects a decline in the number of cases related to commercially purchased pork, recent outbreaks of trichinosis in Iowa and Virginia emphasize the continuing need for education about the dangers of eating inadequately cooked pork. PMID- 1898979 TI - Update: years of potential life lost before age 65--United States, 1988 and 1989. PMID- 1898980 TI - Smoking-attributable mortality and years of potential life lost--United States, 1988. AB - Smoking is a leading cause of diseases associated with premature mortality in the United States; in 1985, these diseases accounted for an estimated 390,000 premature deaths. In this report, mortality data and estimates of smoking prevalence for 1988 are used to calculate smoking-attributable mortality (SAM), years of potential life lost (YPLL), and age-adjusted SAM and YPLL rates for the United States. Calculations were performed using Smoking-Attributable Mortality, Morbidity, and Economic Cost (SAMMEC II) software, which includes relative risk estimates for 22 adult (i.e., greater than or equal to 35 years of age) smoking related diseases and relative risk estimates for four perinatal (i.e., less than 1 year of age) conditions. Age-, sex-, and race-specific mortality data for 1988 were obtained from CDC's National Center for Health Statistics. Data on burn deaths caused by cigarettes were obtained from the Federal Emergency Management Agency. The estimated number of deaths among nonsmokers from lung cancer attributable to passive smoking was obtained from a report of the National Academy of Sciences. Age-, sex-, and race-specific current and former smoking prevalence rates in 1988 for adults aged greater than or equal to 35 years and for women aged 18-44 years were estimated by linear extrapolation using National Health Interview Survey data for 1974-1987. PMID- 1898981 TI - Change of dosing regimen for malaria prophylaxis with mefloquine. PMID- 1898983 TI - Poly(ADP-ribose)polymerase: a perplexing participant in cellular responses to DNA breakage. AB - Poly(ADP-ribose) polymerase is a major nuclear protein of 116 kd, coded by a gene on chromosome 1, that plays a role in cellular responses to DNA breakage. The polymerase binds to DNA at single- and double-strand breaks and synthesizes long branched chains of poly(ADP-ribose), which covalently, but transiently, modifies itself and numerous other cellular proteins and depletes cells of NAD+. This much is known, but the physiological role of the polymerization-degradation cycle is still unclear. Poly(ADP-ribosyl)ation of proteins generally inhibits their function and can dissociated chromatin proteins from DNA. Inhibition of poly(ADP ribose) polymerase increases to toxicity of alkylating agents and some other DNA damaging agents and increases sister-chromatid exchange frequencies. During repair of alkylation damage, inhibition of poly(ADP-ribose) polymerase makes no change in excision of damaged products. increases the total number of repair patches, accelerates the rejoining of DNA breaks, and makes variable increases or decreases in net break frequencies. The polymerization cycle consequently is a major player in the response of cells to DNA breakage, but the game it plays is yet to be explained. PMID- 1898982 TI - In vivo development and in vitro characterization of a subclone of murine P388 leukemia resistant to bis(diphenylphosphine)ethane. AB - Bis(diphenylphosphine)ethane (DPPE) and its gold coordination complexes have demonstrated antitumor activity in transplantable tumor models. This report describes the development of a P388 cell line (P388/DPPEc) that is resistant to DPPE and its analogues and the in vitro characterization of the cross-resistance of this subline to various antitumor and cytotoxic agents. The P388/DPPE tumor cell line was developed by serial transplantation in DPPE-treated mice. Resistance to DPPE was phenotypically stable. The P388/DPPE subline was cross resistant to DPPE analogues and metal coordination complexes of DPPE. In addition, P388/DPPE cells were resistant to several mitochondrial uncouplers, including rhodamine-123, tetraphenylphosphonium, and carbonylcyanide-p-trifluro methoxyphenyl hydrazone. P388/DPPE cells were less capable of sequestering and retaining 123Rh than were sensitive (P388/S) cells. Exposure to Au(DPPE)2+, a gold complex of DPPE with increased antitumor activity, resulted in a depletion of cellular ATP; the depletion was more rapid in the sensitive than the resistant cells. The rate of mitochondrial respiration, as measured by 14CO2 evolution from [6-14C]glucose, was greater in P388/S than in P388/DPPE. As with that evidenced for 123Rh, the cellular uptake of radiolabeled DPPE was decreased in P388/DPPEc cells. The results suggest that the basis for the resistance of this cell line may be an alteration in mitochondrial membrane potential. These data and the striking cross-resistance of P388/DPPE to mitochondrial uncouplers support the hypothesis that mitochondria may be one target involved in the cytotoxic or antitumor activities of these compounds. Mitochondria may also be causally related to the cytotoxic or antitumor activities, in that DPPE may be concentrated in cells via the presence of the inner mitochondrial membrane potential. Thus, P388/DPPE cells can serve as a tool to screen for and evaluate drugs that rely on affecting mitochondrial function, either mechanistically or causally, for their antitumor efficacy. PMID- 1898984 TI - A coat subunit of Golgi-derived non-clathrin-coated vesicles with homology to the clathrin-coated vesicle coat protein beta-adaptin. AB - Four high-molecular-weight proteins form the main subunits of the coat of Golgi derived (non-clathrin) coated vesicles. One of these coat proteins, beta-COP, is identical to a Golgi-associated protein of relative mass 110,000 (110K) that shares homology with the adaptin proteins of clathrin-coated vesicles. This connection, and the comparable molecular weights of the coat proteins of Golgi derived and clathrin-coated vesicles, indicates that they may be structurally related. The identification of beta-COP as the 110K protein explains the blocking of secretion by the drug brefeldin A. PMID- 1898985 TI - Human IgE, IgG4 and resistance to reinfection with Schistosoma haematobium. AB - A well recognized feature of the immune response to parasitic helminth infections, including schistosomiasis, is the production of large amounts of specific and nonspecific IgE1,2. Immunological pathways involving IgE can lead to damage to the developing schistosomulum and it has been suggested that responses involving IgE could have evolved as protection against helminth infections. There has been no epidemiological evidence to support this idea and the only significant IgE responses known in man are those involved in the pathogenesis of allergic disease. Here we measure serological response during reinfection with S. haematobium and demonstrate that IgE antibodies in man can be beneficial. Our results support the hypothesis that the slow build-up of IgE to high levels and the early production of IgG4 antibodies, which may block IgE pathways are responsible for delaying the development of protective immunity to S. haematobium. PMID- 1898986 TI - 'Coatomer': a cytosolic protein complex containing subunits of non-clathrin coated Golgi transport vesicles. AB - Golgi-derived coated vesicles contain a set of coat proteins of relative molecular mass 160,000 (Mr 160K; alpha-COP), 110K (beta-COP), 98K (gamma-COP) and 61K (delta-COP), and several smaller subunits. We have now identified and purified a cytosolic complex containing the same four coat proteins as those of Golgi transport vesicles. We term this complex the Golgi coat promoter or 'coatomer'. The coatomer also contains polypeptides of Mr 36K, 35K and 20K. It represents about 0.2% of soluble cytosolic protein. Gel filtration of unfractionated cytosol indicates that beta-COP resides exclusively in the coatomer complex. The complex seems to be a likely candidate for the unassembled precursor of Golgi coated vesicles, and its purification should help investigations of the role of coat proteins in membrane budding, for which it is necessary to use a refined cell-free system. PMID- 1898987 TI - Expression of anti-DNA immunoglobulin transgenes in non-autoimmune mice. AB - Self-reactive B cells can be regulated by either deletion or inactivation. These manifestations of self-tolerance have been dramatically shown in transgenic mice in which the number of self-reactive cells has been artificially expanded. We have now extended these models to ask if B-cell tolerance as described for non disease-associated antigens also operates for the targets of autoimmunity. The target we have chosen is DNA. Anti-DNA antibodies are diagnostic of certain autoimmune syndromes in humans and are a characteristic of the murine model of systemic autoimmunity, the MRl/lpr mouse. Antibodies to both single-stranded and double-stranded DNA have been implicated in disease. By generating anti-DNA transgenic mice, we have addressed the question of whether DNA-specific B cells are regulated in normal (non-autoimmune) mice. We indeed found that most transgenic B cells bind DNA, yet we failed to detect secreted anti-DNA. We suggest that as a consequence of their self-reactivity these B cells are developmentally arrested. PMID- 1898988 TI - Sterol and triterpene derivatives from plants inhibit the effects of a tumor promoter, and sitosterol and betulinic acid inhibit tumor formation in mouse skin two-stage carcinogenesis. AB - A single topical application of 1 microgram of 12-O-tetradecanoylphorbol- 13 acetate (TPA) to the ears of mice was shown to induce edema, and this TPA-induced inflammation was inhibited by 4-methylsterol and triterpene derivatives. The ED50 of these compounds against TPA-induced inflammation was 0.1-3 mumol. Phytosterols had only slight inhibitory effects. Furthermore, application of 5 micrograms TPA to mouse skin rapidly caused accumulation of ornithine decarboxylase (ODC). Similarly, sitosterol and lupane-type triterpene derivatives markedly inhibited this TPA-induced ODC accumulation. In addition, 5 mumol betulinic acid markedly inhibited the promoting effect of 2.5 micrograms TPA applied twice weekly on skin tumor formation in mice initiated with 50 micrograms of 7,12 dimethylbenz[a]anthracene, and 5 mumol of sitosterol caused slight suppression. Thus, the inhibitory effects of sterol and triterpene derivatives on TPA-induced inflammation roughly parallelled their inhibitory activities against tumor promotion. PMID- 1898989 TI - Infant botulism: a review of 12 years' experience at the Children's Hospital of Philadelphia. AB - Fifty-seven patients with infant botulism were cared for at The Children's Hospital of Philadelphia between 1976 and 1987. The ages of the children ranged from 18 days to slightly more than 7 months. The average duration of hospitalization was 44 +/- 34 days, with the average intensive care unit stay lasting 29 +/- 25 days (54 of 57 patients). The majority (77%) of the patients were ultimately intubated and mechanically ventilated (68%). The principal indication for intubation was loss of protective airway reflexes and not hypercarbia or hypoxemia. In those patients who required mechanical ventilation the average duration was 23 +/- 22 days, with the 10 most severely affected patients (greater than or equal to 28 days of mechanical ventilation) averaging 53 +/- 25 days. Excluding patients ventilated for more than a month, those who underwent tracheostomy were hospitalized nearly twice as long as those who were managed by nasotracheal intubation only (33.5 days vs 63.2 days). The use of continuous nasogastric feedings has supplied most infants with sufficient enteral feedings to avoid weight loss and the need for central intravenous alimentation. PMID- 1898990 TI - Similarities in the modulation of pituitary and prostatic FSH by inhibin and related peptides. AB - Prostatic inhibin peptide (PIP) suppresses the synthesis as well as release of FSH from the rat pituitary whereas the carboxy terminal nonapeptide (86-94) of PIP elevated the release of pituitary FSH. Addition of a tyrosine residue at the NH2-terminal end of nonapeptide and blocking the sulfhydryl group of the cysteine residue at position 87 resulted in a decapeptide having the property of suppressing FSH release from rat pituitary. Human prostate has been shown to synthesize FSH in vitro. PIP, nonapeptide, and decapeptide modulate the prostatic FSH biosynthesis, the pattern of which was similar to that observed for pituitary. PMID- 1898991 TI - Female urethra: MR imaging. AB - The potential of magnetic resonance (MR) imaging in the evaluation of the female urethra was studied in 64 patients. Spin-echo T1- and T2-weighted images were obtained in all 64 patients, and contrast-enhanced T1-weighted images were also obtained in 27 patients. Urethral pathologic conditions, established with urethroscopy or histologic examination, or both, included urethral diverticula, inflammatory granuloma, and primary and metastatic neoplasms. On T2-weighted images, all normal urethras demonstrated a characteristic targetlike appearance with differentiation among the outer ring of low signal intensity, the middle zone of higher signal intensity, and the center of low signal intensity. After injection of gadopentetate dimeglumine, the targetlike appearance of the normal urethra was seen on the T1-weighted images. Urethral diverticula were detected with MR imaging in all nine patients with that diagnosis, and in each, MR imaging demonstrated urethral expansion, distortion of the zonal anatomy, and presence of fluid in the middle zone. Primary or metastatic urethral neoplasms were also detected with MR imaging in every patient with the diagnosis, but differentiation between benign and malignant disease was not possible. Local staging of primary or metastatic malignant disease was correct in eight of the 11 patients. In three patients, the inflammatory changes could not be differentiated from tumor invasion, resulting in overestimation of tumor extent. PMID- 1898992 TI - Distinct protein targets for signals acting at the c-fos serum response element. AB - The c-fos serum response element (SRE) is a primary nuclear target for intracellular signal transduction pathways triggered by growth factors. It is the target for both protein kinase C (PKC)-dependent and -independent signals. Function of the SRE requires binding of a cellular protein, termed serum response factor (SRF). A second protein, p62TCF, recognizes the SRE-SRF complex to form a ternary complex. A mutated SRE that bound SRF but failed to form the ternary complex selectively lost response to PKC activators, but retained response to PKC independent signals. Thus, two different signaling pathways act through discrete nuclear targets at the SRE. At least one of these pathways functions by recruitment of a pathway-specific accessory factor (p62TCF). These results offer a molecular mechanism to account for the biological specificity of signals that appear to act through common DNA sequence elements. PMID- 1898993 TI - Signal transduction by interferon-alpha through arachidonic acid metabolism. AB - Molecular mechanisms that mediate signal transduction by growth inhibitory cytokines are poorly understood. Type I (alpha and beta) interferons (IFNs) are potent growth inhibitory cytokines whose biological activities depend on induced changes in gene expression. IFN-alpha induced the transient activation of phospholipase A2 in 3T3 fibroblasts and rapid hydrolysis of [3H]arachidonic acid (AA) from prelabeled phospholipid pools. The phospholipase inhibitor, bromophenacyl bromide (BPB), specifically blocked IFN-induced binding of nuclear factors to a conserved, IFN-regulated enhancer element, the interferon-stimulated response element (ISRE). BPB also caused a dose-dependent inhibition of IFN-alpha induced ISRE-dependent transcription in transient transfection assays. Specific inhibition of AA oxygenation by eicosatetraynoic acid prevented IFN-alpha induction of factor binding to the ISRE. Treatment of intact cells with inhibitors of fatty acid cyclooxygenase or lipoxygenase enzymes resulted in amplification of IFN-alpha-induced ISRE binding and gene expression. Thus, IFN alpha receptor-coupled AA hydrolysis may function in activation of latent transcription factors by IFN-alpha and provides a system for studying the role of AA metabolism in transduction of growth inhibitory signals. PMID- 1898994 TI - The rush to publish. PMID- 1898995 TI - Responses of rat basilar artery to acetylcholine and platelet products in vivo. AB - Studies in vitro suggest that the basilar artery has distinctive responses to endothelium-dependent stimuli. Our first goal was to examine the effects of acetylcholine on diameter of the basilar artery in vivo. Because aggregating platelets may have important effects on cerebral arteries, our second goal was to examine the effects on the basilar artery of products that are released by platelets (thromboxane, serotonin, and adenosine 5'-diphosphate). Diameter of the basilar artery was measured through a cranial window in anesthetized rats (n = 25). Baseline diameter of the basilar artery was 247 +/- 10 microns mean +/- SEM. Topical application of acetylcholine at 10(-6) and 10(-5) M dilated the basilar artery by 13 +/- 2% and 19 +/- 2%, respectively. The thromboxane analogue U46619 at 10(-8) and 10(-7) M reduced the diameter of the basilar artery by 18 +/- 5% and 29 +/- 4%, respectively. At 10(-8) and 10(-7) M, serotonin had little effect on pial arterioles on the cerebrum but constricted the basilar artery by 18 +/- 2% and 29 +/- 4%, respectively. At 10(-6) and 10(-5) M, adenosine 5'-diphosphate produced marked dilatation of pial arterioles on the cerebrum (9 +/- 2% and 20 +/ 3%, respectively) but had little effect on the basilar artery (increased diameter by 4 +/- 2% and 6 +/- 2%, respectively). Thus, in contrast to some studies of the basilar artery in vitro, acetylcholine produces dilatation of the basilar artery in vivo. Potent constrictor responses to thromboxane and serotonin, in combination with the minimal dilator effect of adenosine 5' diphosphate, suggest that release of these products during platelet aggregation would favor constriction of the basilar artery. PMID- 1898996 TI - Effect of cyclosporine on T lymphocyte development. Relationship to syngeneic graft-versus-host disease. AB - This report investigates the effects of cyclosporine on the reconstitution of T lymphocytes after syngeneic bone marrow transplantation and its role in the development of a novel T cell-mediated autoimmune disease, syngeneic graft versus host disease. We analyzed the effect of CsA treatment on T lymphocyte differentiation during reconstitution after bone marrow transplantation and correlated the maturation of CD4+ and CD8+ T cell subsets with the onset of syngeneic GVHD. Administration of CsA following syngeneic bone marrow transplantation leads to a developmental arrest of mature CD4+ and CD8+ T lymphocytes in the thymus and a marked reduction in cells expressing the alpha beta T cell receptor. The reduction of CD4+ and CD8+ T cell subsets is also reflected in the peripheral lymphoid compartment with an altered CD4/CD8 ratio. Functional assessment of the cells revealed that CD8+ cells respond normally to mitogenic signalling whereas CD4+ cells exhibit marginal proliferative responses. Both subsets of T lymphocytes respond to syngeneic B lymphoblasts, comparable to the response of T lymphocytes from non-CsA-treated syngeneic BMT recipients, suggesting that autoreactive cells are produced despite CsA treatment. Following discontinuation of CsA, T cell differentiation in the thymus is rapidly restored to normal. However, concurrent with the onset of syngeneic GVHD, a compensatory insurgence of CD4+ T helper cells is observed. PMID- 1898997 TI - The unstable ST segment early after thrombolysis for acute infarction and its usefulness as a marker of recurrent coronary occlusion. AB - To investigate the incidence of early recurrent ST elevation after intravenous thrombolytic therapy for acute myocardial infarction, 12-lead electrocardiograms were continuously monitored for 571 +/- 326 minutes in 31 patients presenting within 4 hours of symptom onset. The study group comprised 9 women and 22 men (mean age +/- standard deviation 53 +/- 12 years), with ST elevation (anterior in 15, inferior in 16) on the initial electrocardiogram, who were given either tissue plasminogen activator (22 patients) or streptokinase (9 patients). Angiography was performed in 30 of 31 patients at 7 to 10 days. Early (less than 3 hours) resolution of ST elevation occurred in 19 patients (61%) at a median of 94 minutes (interquartile range 57 to 113) after thrombolysis, whereas 12 (39%) had no or late (greater than 6 hours) resolution. Eleven of the 19 with early resolution (58%) had either transient (5 patients) or sustained (6 patients) recurrences of ST elevation. Recurrent ST elevation was equal to or more than the initial peak elevation in 9 of 11 patients, and greater than 75% of initial peak in 2. A total of 25 episodes of recurrent ST elevation were observed in the 11 patients (19 transient and 6 sustained episodes), of which 8 (32%) were silent. The proportion of silent episodes was similar for transient (35%) and sustained (33%) recurrences. All patients with sustained recurrent ST elevation had at least 1 preceding transient recurrence. The median duration of transient recurrent ST elevation was 43 minutes (28 to 63).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1898998 TI - Reversion of recent-onset atrial fibrillation to sinus rhythm by intravenous flecainide. AB - Spontaneous reversion to sinus rhythm is a frequent occurrence in recent-onset atrial fibrillation (AF). In a randomized, double-blind, controlled study, intravenous flecainide (2 mg/kg, maximum dose 150 mg) was compared with placebo in the treatment of recent-onset AF (present for greater than or equal to 30 minutes and less than or equal to 72 hours' duration and a ventricular response greater than or equal to 120 beats/min). Intravenous digoxin (500 micrograms) was administered concurrently to all patients in both groups who had not previously taken digoxin. The trial medication was administered over 30 minutes. Exclusion criteria included hemodynamic instability, severe heart failure, recent antiarrhythmic therapy, hypokalemia and pacemaker dependence. One hundred two consecutive patients with recent-onset AF were enrolled in the study. All patients underwent continuous electrocardiographic monitoring in the intensive care or coronary care unit. Twenty-nine (57%) patients given flecainide and digoxin, but only 7 (14%) given placebo and digoxin, reverted to sinus rhythm in less than or equal to 1 hour after starting the trial medication infusion and remained in stable sinus rhythm (chi-square 18.9, p = 0.000013; odds ratio 8.3, 95% confidence interval 2.9 to 24.8). At the end of the 6-hour monitoring period, 34 patients (67%) in the flecainide-digoxin group were in stable sinus rhythm, whereas only 18 patients (35%) in the placebo-digoxin group had reverted (chi square 8.83, p = 0.003; odds ratio 3.67, 95% confidence interval 1.5 to 9.1).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1898999 TI - A pilot study of three sequential chemotherapeutic regimens in metastatic breast cancer. AB - The aim of this pilot study was to estimate the toxicity and response rate of an alternating chemotherapeutic program in chemotherapy-naive metastatic breast cancer patients. Treatment consisted of regimen A (given days 1-28): cyclophosphamide 100 mg/m2 PO days 1-14, doxorubicin 30 mg/m2 i.v. days 1 and 8, and 5-fluorouracil 500 mg/m2 i.v. days 1 and 8 (CAF regimen); regimen B (given days 29-56): dibromodulcitol 135 mg/m2 p.o. days 30-39, mitoxantrone 9 mg/m2 i.v. day 29, and vincristine 1.2 mg/m2 i.v. (maximum 2.0 mg) day 29 (DMV regimen); and regimen C (given days 57-84): thiotepa 12 mg/m2, doxorubicin 45 mg/m2 and vinblastine 4.5 mg/m2 all i.v. on day 57. There were 27 eligible patients with a median age of 51 years (range 34-78). On 14 episodes the leukocyte count fell to less than 1 X 10(9)/L during the first six cycles of treatment (14% of 99 cycles). There were no treatment-related deaths. Common non-life-threatening toxicities included thrombocytopenia, anemia, vomiting, and alopecia. Despite having no drugs in common, the leukocyte and platelet nadirs after CAF correlated with the nadir counts after DMV (r values of 0.6829 and 0.5892, respectively; p = 0.01). Among the 23 patients with measurable and/or evaluable disease there were five complete responses (22%) and nine partial responses (39%), with a median time to treatment failure of 29 weeks. The overall median survival was 19 months. PMID- 1899000 TI - Interleukin-2 and interferon-gamma production in follicular lymphomas. AB - In situ hybridization with specific RNA radiolabeled probes was used to analyze the production of interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) by 21 low grade follicular lymphomas (FLs). All of the 21 FLs tested contained lymphokine synthesizing cells in the interfollicular and follicular areas. Enumeration of lymphokine synthesizing cells indicated heterogeneous IL-2 production among lymph nodes tested; 2 of the 21 had much higher densities of IL-2-producing cells (855 and 570/cm2) than did the remaining 19 (mean, 92 +/- 15/cm2). IFN-gamma-producing cells displayed no such variation (mean, 77 +/- 8 IFN-gamma-producing cells/cm2). The mean IL-2/IFN-gamma-producing cell ratio was 2.69 +/- 0.84, indicating preferential induction of IL-2. The detailed distribution of lymphokine-producing cells showed that IL-2 and IFN-gamma-producing cells were located mainly in the follicular areas. The mean follicular/interfollicular ratio was 1.82 +/- 0.16 for IL-2 and 1.92 +/- 0.19 for IFN-gamma-producing cells. The results show that T cell activation, defined by lymphokine production, occurs in FL lymph nodes in direct contact with malignant B cells. Thus, lymphokine production may play an important role in the control of tumor growth, which is the result of interaction between tumor cells and host-derived immune reaction. PMID- 1899001 TI - Cortical and subcortical patterns of synaptophysinlike immunoreactivity in Alzheimer's disease. AB - Quantification of synaptophysinlike immunoreactivity is a valuable method for studying the presynaptic terminals in the normal and damaged nervous system. The present report shows that in the control brain, the predominant pattern of synaptic immunostaining in the neocortex was that of an evenly distributed densely granular immunolabeling of the neuropil, while in the paleocortex and in subcortical areas of the brain most of the presynaptic terminals were distributed along the dendritic arborizations or around the neuronal somata. The immunochemical and the immunohistochemical analysis of the Alzheimer's disease tissue showed that the frontal and parietal cortex presented the most severe and widespread loss, with a 45% loss in synaptophysin immunoreactivity. These areas showed an average 35% loss of large neurons. The visual cortex, hippocampus, entorhinal cortex, nucleus basalis of Meynert, and locus ceruleus displayed some degree of loss, but to a lesser extent. In addition to this loss, the basic patterns of organization of the presynaptic terminals were altered, with the presence of abundant, enlarged synaptophysin-labeled terminals. This study further supports the role of synaptic pathology in Alzheimer's disease. PMID- 1899002 TI - Vasopressin depolymerizes F-actin in toad bladder epithelial cells. AB - Vasopressin (AVP) induces the rapid fusion of water channel-containing vesicles with the luminal membrane of its target cell. We have carried out a quantitative study of the F-actin content of toad bladder epithelial cells, using the rhodamine phalloidin binding assay. As early as 1 min after AVP stimulation, there is a significant 15% reduction of cellular F-actin, which remains reduced by 20-30% for the duration of action of AVP. Comparable reductions were seen following 8-bromoadenosine 3',5'-cyclic monophosphate, 1-desamino-8-D-arginine vasopressin, and forskolin. F-actin content rose to and then exceeded that of control bladders after AVP washout. Inhibition of prostaglandin synthesis enhanced both water flow and the decrease of F-actin. In the living cell, stabilization of F-actin with NBD-phallacidin selectively inhibited water flow. In view of the rapidity of the response, we conclude that AVP shifts the equilibrium between F-actin and G-actin monomers, and this depolymerization may be required for vesicle fusion. PMID- 1899003 TI - Effects of continuous graded total parenteral nutrition on feeding indexes and metabolic concomitants in rats. AB - The influence of graded amounts of total parenteral nutrition (TPN) on food intake and feeding indexes was investigated in 90 rats housed in Automated Computerized Rat Eater Meter metabolic cages with free access to water and chow. When food intake was stable after catheter placement, 10 control rats continued with the 3 ml/h normal saline used for catheter patency, whereas study rats were given graded TPN continuously for 3 days, amounting to the equivalent of 26% (TPN 26), 53% (TPN-53), 81% (TPN-81), or 114% (TPN-114) of their daily caloric needs. TPN consisted of glucose, fat, and amino acids in the caloric ratio of 50:30:20. In study rats, the graded TPN depressed food intake, meal number, meal size, and eventually food consumption rate, meal sniffs, and intermeal sniffs in a dose- and time-dependent manner. During graded TPN, rats decreased total food intake by eating fewer, smaller, shorter meals at a decreasing consumption rate; sniffing activities were correspondingly curtailed. Stopping TPN led to normalization of feeding indexes. Blood glucose did not change while plasma insulin rose with graded TPN. A decrease in hepatic glycogen and an increase in hepatic triglycerides occurred. Plasma valine, phenylalanine, and methionine rose in a TPN dose-dependent manner. TPN-26 and TPN-53 significantly decreased whole brain amino acids; with TPN-114 no change occurred. Brain influx of tryptophan remained unchanged, but a progressive decrease in brain influx of tyrosine occurred. Whole brain dopamine and serotonin were depressed with TPN-26 and TPN-81 but were normal with TPN-114.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1899004 TI - Thyrotropin-releasing hormone in ovine fetus: ontogeny and effect of thyroid hormone. AB - The ontogenesis of hypothalamic and extrahypothalamic thyrotropin-releasing hormone (TRH) and the effect of altered thyroid status on tissue TRH levels were studied in fetal sheep. At 62 days gestation (term = 145 days) TRH was detectable in serum and in hypothalamic, placental, and pancreatic tissues; pancreatic, placental, and serum levels exceeded hypothalamic levels two- to fivefold. Analysis of tissues obtained from 88-day gestation fetuses were comparable: TRH levels in placenta (54 +/- 15 pg/mg tissue protein), pancreas (34 +/- 5 pg/mg protein), and serum (93 +/- 9 pg/ml) exceeded those in hypothalamic extracts (15 +/- 9 pg/mg protein). By 120 days gestation, TRH values in the hypothalamus (610 +/- 52 pg/mg protein) exceeded those in extrahypothalamic sites; values were comparable at 140 days gestation. Fetal thyroidectomy resulted in a 2-fold elevation of hypothalamic TRH concentrations (1,030 +/- 139 vs. 522 +/- 29 pg/mg protein) and 2 to 20-fold elevations of TRH in the placenta (147 +/- 23 vs. 42 +/ 8 pg/mg protein), pancreas (195 +/- 11 vs. 29 +/- 7 pg/mg protein), duodenum (363 +/- 97 vs. 29 +/- 7 pg/mg protein), and serum (2,563 +/- 212 vs. 131 +/- 16 pg/ml). 3, 5, 3'-Triiodothyronine (T3) infusion in thyroidectomized fetuses resulted in elevated serum T3 values (480 +/- 80 ng/dl) and suppressed hypothalamic TRH (249 +/- 68 vs. 522 +/- 29 pg/mg protein) and serum TRH concentrations (30 +/- 4 vs. 131 +/- 156 pg/ml). Placental, pancreatic, and duodenal TRH concentrations in thyroidectomized T3-infused animals were below the level of detection of the assay (5 pg/mg tissue protein).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1899005 TI - Energy equivalents of CO2 and their importance in assessing energy expenditure when using tracer techniques. AB - Carbon dioxide production in free living animals and humans can be measured using tracer techniques, but the prediction of energy expenditure also requires an estimate of the energy equivalents of CO2 (energy expended/CO2 produced; EeqCO2). This work is concerned with assessing the variation in EeqCO2 with the use of dietary information, indirect calorimetry, and theoretical concepts. The EeqCO2 for diets (EeqCO2 diet) ingested by 63 individuals living in a Cambridgeshire village, UK, was found to vary by less than 10%. The EeqCO2 diet for different populations varied by greater than 10% and for artificial enteral feeds by approximately 20%. Alcohol increases this variability because it has a particularly high EeqCO2. Variation in the nitrogenous end products of metabolism may also have a substantial effect on the EeqCO2 for a subject (EeqCO2 body), especially when a large proportion of energy expenditure is derived from protein oxidation, as in strict carnivores. Nutrient/energy imbalances such as those associated with growth, hypercaloric feeding, or starvation may also have major effects on EeqCO2 body. It is concluded that the calculation of energy expenditure from CO2 production should not employ a universal value for EeqCO2 body. The value should take into account the physiological and clinical state under investigation. Practical recommendations are suggested. PMID- 1899006 TI - Inositol phosphate formation and [Ca2+]i in secretagogue-stimulated rabbit gastric mucous cells. AB - The formation of inositol phosphates and the changes in free intracellular Ca2+ ([Ca2+]i) in isolated rabbit gastric mucous cells during cholinergic stimulation were examined and the potential role of inositol phosphate turnover and [Ca2+]i in gastric mucus secretion evaluated. Rabbit chief and parietal cells were studied for comparison. The formation of [3H]inositol phosphates in mucous, chief, and parietal cells was stimulated in a time- and concentration-dependent fashion by acetylcholine (ACh). The ACh-induced initial [Ca2+]i peak was maximally (10(-4) M ACh) 199 +/- 8% of basal in mucous cells, 427 +/- 20% in chief, and 455 +/- 31% in parietal cells and was followed by a lower-level plateau in mucous and parietal cells but by a more rapid decline in chief cells. As in parietal and chief cells, the initial [Ca2+]i peak occurred in mucous cells in the absence of external Ca2+. ACh stimulated a mucous cell membrane Ca2(+) entry mechanism in addition to release of Ca2+ from intracellular stores. The concentration-response relationships for the production of [3H]-inositol phosphates, the initial rise in [Ca2+]i, and the stimulation of glycoprotein secretion by ACh were virtually identical. Suppression of the [Ca2+]i rise by the intracellular Ca2(+)-chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) abolished the secretory response. As with many other secretory cells, gastric mucous cells possess cholinergic receptors that upon stimulation mediate the hydrolysis of phosphoinositides, a release of Ca2+ from intracellular stores, and a stimulation of Ca2+ influx through the plasma membrane. PMID- 1899007 TI - Mesolimbic dopamine mediates gastric mucosal protection by central neurotensin. AB - Bilateral microinjection (1.0 microliter/side) of neurotensin (NT; 0.3, 1.5, and 3.0 micrograms/side) into the nucleus accumbens (NACB) and ventral tegmental area (VTA) but not in substantia nigra and striatum reduced gastric mucosal injury produced by 2 h of cold-water restraint (CWR). The minimal effective dose for NT induced protection was 10-100 times lower when administered directly into NACB than into the lateral ventricle. These effects were blocked by pretreatment with the dopamine (DA) receptor antagonist, haloperidol (Hal; 0.5 microgram/side) given directly into NACB. Injection of 6-hydroxydopamine into VTA depleted endogenous DA and inhibited gastric mucosal protection against CWR-induced injury afforded by NT pretreatment. NT, given into either VTA and NACB, inhibited pentagastrin-stimulated gastric acid secretion. These results suggest that VTA and NACB, which represent the mesolimbic DA system, are important locations for interaction between NT and DA receptors to produce gastric mucosal protection against CWR-induced injury. PMID- 1899008 TI - CRF triggers the CNS release of TRH in stress-induced changes in gastric emptying. AB - Stress elicited by exposure to cold induces an increase of gastric emptying (GE) and intestinal transit of a caloric meal in mice and the release of corticotropin releasing factor (CRF) and thyrotropin-releasing hormone (TRH) in the central nervous system (CNS). The present study proposed 1) to compare in mice the central effects of TRH, CRF, and cold-exposure stress on GE and intestinal transit of a caloric test meal consisting of 0.5 ml of reconstituted milk marked with 51Cr-labeled sodium chromate, and 2) using CRF and TRH antisera to determine whether TRH and CRF act in cascade or independently. The intracerebroventricular (icv) injection of TRH (0.5 microgram/kg) and CRF (1 microgram/kg), as well as cold stress, significantly increased GE, whereas 10-fold higher doses injected intraperitoneally were ineffective. The effect of cold stress on GE was abolished by prior icv injection of both CRF and TRH antisera. The effect of TRH was not blocked by CRF antiserum, but TRH antiserum suppressed the increase in GE induced by CRF. Moreover, both CRF and TRH antisera abolished changes in the rate of GE induced by exogenous CRF and TRH injection, respectively, therefore demonstrating the specific efficiency of immunoneutralization. CRF and cold stress both induced an increase in the rate of intestinal transit, while TRH had no effect. Antibodies to CRF prevented the intestinal stimulatory effect induced by CRF and cold stress. In contrast, antibodies to TRH were unable to antagonize either CRF or cold-stress induced increase in the rate of intestinal transit.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1899009 TI - Excitation of neurons in the medullary raphe increases gastric acid and pepsin production in cats. AB - The nucleus raphe obscurus (NRO) has recently emerged as an important nucleus for excitation of gastric motor activity through projections to the dorsal motor nucleus of the vagus (DMV) [P. J. Hornby, C. D. Rossiter, R. L. White, W. P. Norman, D. H. Kuhn, and R. A. Gillis. Am. J. Physiol. 258 (Gastrointest. Liver Physiol. 21): G91-G96, 1990; and M. J. McCann, G. E. Herman, and R. C. Rogers. Brain Res. 486: 181-184, 1989]. A neurotransmitter thought to be involved in this NRO-DMV pathway is thyrotropin-releasing hormone (TRH), a peptide that excites gastric activity when microinjected into the DMV. The purpose of the present study was to determine whether gastric acid and pepsin secretion were altered by 1) activation of neurons in the NRO by microinjection of kainic cid and 2) microinjection of TRH into the DMV in chloralose-anesthetized cats. Microinjection of kainic acid into the NRO increased gastric acid secretion [baseline was 6 +/- 2 (mu eq) H+/15 min (n = 7) and increased to 8 +/- 2, 26 +/- 11 (P less than 0.05), and 21 +/- 7 mu eq/15 min (P less than 0.05) during the first, second, and third 15-min periods after microinjection, respectively]. Pepsin output also increased from a baseline of 287 +/- 67 pepsin units (PU) (n = 4) to 507 +/- 126 PU 15 min postinjection, 541 +/- 118 PU 30 min after injection (P less than 0.05), 608 +/- 92 PU 45 min after injection (P less than 0.05), and 700 +/- 156 PU 60 min postinjection (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1899010 TI - Cold agglutinin autoantibodies in psychiatric patients: their relation to diagnosis and pharmacological treatment. AB - BACKGROUND AND METHOD: The purpose of this study was to compare titers of cold agglutinins in schizophrenic patients with those in patients with major affective disorders and in normal healthy subjects. One hundred sixty-six psychiatric patients and 37 healthy comparison subjects were included in the study. Ninety of the patients suffered from schizophrenia, 54 from bipolar disorder, and 22 from major depression. Venous blood samples were obtained from all subjects between 8:00 and 10:00 a.m. and were immediately tested for cold agglutinin titers. RESULTS: A high frequency (42.2%) of positive cold agglutinin titers was detected in the schizophrenic patients, compared with the bipolar (11.1%) and unipolar (9.0%) patients and the comparison group (8.1%). The investigators did not find any pharmacological effect on these results. CONCLUSIONS: The findings suggest that, at least in this group, positive cold agglutinin titers are associated with schizophrenia. However, this observation cannot provide direct evidence for the involvement of viral or autoimmune factors in schizophrenia. PMID- 1899011 TI - Clenbuterol plus acivicin decrease tumor growth and increase muscle mass in rats maintained on total parenteral nutrition. AB - Two problems associated with supplemental nutrition of tumor-bearing organisms are control of tumor growth and reduction of cachexia. To investigate these problems, rats bearing methylcholanthrene-induced sarcomas were maintained on total parenteral nutrition (TPN) for 10 to 12 days beginning 23 days after tumor inoculation. Combined treatment of one group of these rats with the glutamine antimetabolite, acivicin, and the beta 2-adrenergic agonist, clenbuterol, arrested tumor growth, increased skeletal muscle mass and protein content, increased gut mass, and decreased total plasma lipid levels. Resting energy expenditure and cardiac mass were increased by TPN and were increased further by acivicin plus clenbuterol. These results demonstrate that tumor growth and muscle wasting can be controlled during TPN of tumor-bearing organisms. Therefore, cachectic depletion of lean body tissue may not be obligatory in neoplastic disease. PMID- 1899012 TI - Delayed access to health care: risk factors, reasons, and consequences. AB - OBJECTIVE: To determine characteristics of patients reporting delays in care before hospitalization and the reasons for those delays. DESIGN: Survey; personal interviews. SETTING: Five hospitals in Massachusetts. PATIENTS: Subjects were drawn from a consecutive sample of all adult patients (excluding obstetrics or psychiatry patients) hospitalized during the first 6 months of 1987 as part of a larger study of hospital costs. For the current study, if patients were re admitted, we included in our analysis only data on the first admission during the study period. We obtained usable survey data from 12,068 of 17,231 eligible patients. RESULTS: Delays in care were reported by 16% of patients. The odds of reporting delays in care among patients who were black, poor, uninsured, or without a regular physician were 40% to 80% greater than those for other patients (P less than 0.01). Most patients who reported delays thought that their problem was not serious (64%). Cost was an important factor in delaying care for patients in lower socioeconomic positions; the odds of delaying care because of cost for patients who were both poor and uninsured were 12 times greater than the odds for other patients (P less than 0.001). After controlling for diagnosis-related groups (DRGs) and severity, patients who reported delays had 9% longer hospital stays compared with others (P less than 0.001). CONCLUSIONS: Patients generally thought to be disadvantaged are at especially high risk for delaying care for conditions that eventually lead to hospitalization. Because these delays are associated with longer hospital stays and potentially poorer health outcomes, interventions that reduce delays seem especially important. PMID- 1899013 TI - Diarrhea after misoprostol in Crohn disease. PMID- 1899014 TI - [In-vivo 19F-MRS study of 5-fluorouracil (5-FU) metabolism on tumors]. AB - 5-Fluorouracil (5-FU) metabolism on tumors was studied by in-vivo 19F-MRS (magnetic resonance spectroscopy). In this study, two kinds of tumors were used, i.e., Yoshida sarcoma implanted subcutaneously to the abdomen of rats and drug induced tumors in the rats livers. Sequential 19F spectra were obtained just after 150 mg/kg 5-FU injected intravenously. In Yoshida sarcoma, the accumulation of 5-FU was observed and disappearance of 5-FU was slower compared to the normal tissue. However, synthesis of fluoronucleotides (Fnct) could not be detected. In drug-induced liver tumors, the peak of fluoro-beta-alanine (FBAL) was observed. Disappearance of 5-FU and catabolism to FBAL in the liver tumors group were slower compared to the normal liver. Synthesis of Fnct did not increase in the liver tumor group. The results in the liver tumor group are considered to be the confined result of the hepatocytes and tumors cells. It was considered that the delayed catabolism to FBAL in the liver tumor group showed metabolic dysfunction of the liver. Also the synthesis of Fnct in tumors could not be detected by in vivo 19F-MRS. 19F-MRS method could not detect Fnct in tumors in-vivo. However, the accumulation of 5-FU could be assessed by this method. It is expected that the evaluation of 5-FU pooling in tumors could be used for the index of chemotherapeutic effect. PMID- 1899015 TI - T-gamma-lymphoproliferative disorder arising in a background of autoimmune disease and terminating in plasma cell dyscrasia with primary amyloidosis. AB - T-gamma-lymphoproliferative disorder, a syndrome of T-cell lymphocytosis with neutropenia has been described in patients with various autoimmune disorders, especially rheumatoid arthritis. We report a case of T-gamma-lymphoproliferative disorder occurring in a 42-year-old white woman with a long history of dermatitis herpetiformis and subsequent development of Coomb's positive autoimmune hemolytic anemia and polymyositis. The peripheral blood lymphocytes showed the T-suppressor cell phenotype (CD2-, CD3-, CD8-, and CD4-). DNA analysis of the peripheral blood lymphocytes revealed a T-cell receptor beta-chain gene rearrangement and an immunoglobulin heavy-chain gene rearrangement. The patient's course was marked by numerous bouts of infection. The unique factor in this patient was the development of a plasma cell dyscrasia and amyloidosis prior to death. PMID- 1899016 TI - The relationship of neonatal alimentation practices to the occurrence of endemic necrotizing enterocolitis. AB - Enteric alimentation has been one of several factors implicated in the development of necrotizing enterocolitis (NEC). To examine this relationship further, the alimentation records of 19 patients who developed NEC were each compared with two matched patients controlled for birthweight and time of admission to the intensive care nursery. Parameters compared included total fluids provided, rate of enteral feed volume advancement, milk selection, and medications given. In addition, because there were no marked day-to-day differences between the mean values of most parameters and because we noted a marked fluctuation of formula intake and volume increments, we analyzed the maximum differences between the two groups. Maximum total fluids intake occurred on day 5 of life for the NEC patients and was 180.7 +/- 44 ml/kg. The control group on this same day received 149.7 +/- 35 ml/kg (p less than 0.01). Maximum enteral intake occurred on day 8 for the NEC patients at 124.3 +/- 5.7 ml/kg, whereas the control group had consumed only 83.5 +/- 60 ml/kg (p less than 0.05) on this matched day. The feed increment rate from initiation of feeds to day of maximum feeds was 27.8 +/- 16 ml/kg/day for the NEC patients and 16.8 +/- 11 for the control patients (p less than 0.0005). Furthermore, during the entire study period patients who developed NEC had the greatest 1 day increment compared with the controls (56.7 +/- 19.4 vs 44.6 +/- 26.2 ml/kg, p less than 0.05). Very rapid advancement of enteral feedings and excessive fluid volumes may predispose premature infants to the development of NEC and should be discouraged.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1899018 TI - Electronic energy transfer and fluorescence quenching in the active sites of mercuric reductase. AB - The FAD-containing enzyme mercuric reductase has been studied by means of steady state and time-resolved fluorescence spectroscopy. The fluorescence relaxation of the excited state of the isoalloxazine ring of FAD can be described by a sum of two exponential functions. The two lifetimes are not due to a different lifetime of each of the two FAD molecules of mercuric reductase. The FAD molecules are quenched dynamically by a quencher that is not sensitive to the solvent viscosity. In vitro activation induces a dynamic quenching of fluorescence, while upon binding of NADP+ the FAD molecules are both statically and dynamically quenched. Time-resolved fluorescence anisotropy experiments of mercuric reductase in water show that the isoalloxazine ring probably undergoes a rapid and restricted vibrational motion of small amplitude. Electronic energy transfer occurs between the two FAD molecules at a rate of about 3.4 x 10(7) s-1. The angle between the emission transition dipole of the donor and the absorption transition dipole of the acceptor is 137 +/- 2 degrees (or 43 +/- 2 degrees). From previous X-ray data of glutathione reductase we find that the corresponding angle is 160 degrees. This suggests that the isoalloxazine rings of mercuric reductase and glutathione reductase are mutually tilted in slightly different ways. PMID- 1899017 TI - Passage state affects arachidonic acid content and eicosanoid release in porcine aortic endothelial cells. AB - Porcine aortic endothelial cells were cultured through four passages from primary cultures. The arachidonic acid content of individual phospholipid classes and the release of 6-keto-prostaglandin F1 alpha and 15-hydroxyeicosatetraenoic acid in response to 1 microM ionophore A23187 were assayed at each passage. The content of arachidonic acid in phosphatidylinositol and diacyl phosphatidylethanolamine remained constant at passage 1 but declined at passage 2 by approximately 29% and at passage 4 by approximately 59%. The release of 6-keto-prostaglandin F1 alpha was also unchanged at passage 1 but decreased by 60% at passage 2 and by 82% from its original value at passage 4. In contrast, the arachidonic acid content of diacyl phosphatidylcholine and of alkenyl phosphatidylethanolamine decreased with each passage, by 34% at passage 1, 59% at passage 2, 71% at passage 3, and 76% of the original value at passage 4. Stimulation with arachidonic acid reversed the passage effect. The release of 15-hydroxyeicosatetraenoic acid decreased by 82% at passage 1 and diminished to a 97% decrement from the original value by passage 4. When stimulated with arachidonic acid, 15-hydroxyeicosatetraenoic acid steadily decreased by approximately 70% at passages 3 and 4. The data indicate that passage state strikingly and nonuniformly affects phospholipid class arachidonic acid content and eicosanoid release in response to agonist stimulation. PMID- 1899020 TI - Rhodopsin in dimyristoylphosphatidylcholine-reconstituted bilayers forms metarhodopsin II and activates Gt. AB - The photochemical intermediate metarhodopsin II (meta II; lambda max = 380 nm) is generally identified with rho*, the conformation of photolyzed rhodopsin which binds and activates the visual G-protein, Gt [Emeis, D., & Hoffman, K.P. (1981) FEBS Lett. 136, 201-207]. Purified bovine rhodopsin was incorporated into vesicles consisting of dimyristoylphosphatidylcholine (DMPC), and the rapid formation of a photochemical intermediate absorbing maximally at 380 nm was quantified via both flash photolysis and equilibrium spectral measurements. Kinetic and equilibrium spectral measurements performed above the Tm of DMPC showed that Gt, in the absence of GTP, enhances the production of the 380-nm absorbing species while reducing the concentration of the 478-nm-absorbing species, metarhodopsin I (meta I), in a manner similar to that observed in the native rod outer segment disk membrane. This Gt-induced shift in the equilibrium concentration of photointermediates indicated that the species with an absorbance maximum at 380 nm was meta II. The presence of rho* in the DMPC bilayer was established via measurements of photolysis-induced exchange of tritiated GMPPNP, a nonhydrolyzable analogue of GTP, on Gt. Above Tm, the metarhodopsin equilibrium is strongly shifted toward meta I relative to the native rod outer segment disk membrane; however, at 37 degrees C, 40% of the photointermediates are in the form of meta II. The formation of meta II above Tm is slowed by a factor of ca. 2 relative to the disk membrane. Below Tm, the equilibrium is shifted still further toward meta I, and meta II forms ca. 7 times slower than in the disk membrane.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1899019 TI - Complete assignment of the methionyl carbonyl carbon resonances in switch variant anti-dansyl antibodies labeled with [1-13C]methionine. AB - A 13C NMR study is reported of switch variant anti-dansyl antibodies developed by Dangl et al. [(1982) Cytometry 2, 395-401], who had used the fluorescence activated cell sorter to select and clone these variants. These switch variant antibodies possess the identical VH, VL, and CL domains in conjunction with different heavy chain constant regions. In the present study, switch variant antibodies of IgG1, IgG2a, and IgG2b subclasses were used along with a short chain IgG2a antibody, in which the entire CH1 domain is deleted. The switch variant antibodies were specifically labeled with [1-13C]methionine by growing hybridoma cells in serum-free medium. Assignments of all the methionyl carbonyl carbon resonances have been completed by using the intact antibodies along with their fragments and recombined proteins in which either heavy or light chain is labeled. A double labeling method [Kainosho, M., & Tsuji, T. (1982) Biochemistry 21, 6273-6279] has played a crucial role in the process of the spectral assignments. The strategy used for the assignments has been described in detail. In incorporating 15N-labeled amino acids into the antibodies for the double labeling, isotope dilution caused a serious problem except in the cases of [alpha 15N]lysine and [15N]threonine, both of which cannot become the substrate of transaminases. It was found that beta-chloro-L-alanine is most effective in suppressing the isotope scrambling. So far, spectral assignments by the double labeling method have been possible with 15N-labeled Ala, His, Ile, Lys, Met, Ser, Thr, Tyr, and Val.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1899022 TI - Substitution of histidine-84 and the GTPase mechanism of elongation factor Tu. AB - Mutation of His84, a residue situated in one of the loops forming the guanine nucleotide binding pocket, was introduced in the G domain, the isolated N terminal half molecule of bacterial elongation factor Tu (EF-Tu), in order to investigate the role of this residue on the basic activities of EF-Tu: the interaction with GDP and GTP and the hydrolysis of GTP. Substitution of His84 by Gly reduces the GTPase activity of the G domain to 5%; this activity can still be stimulated by raising the KCl concentration as the activity of wild-type G domain or the intact molecule. Since the affinities of the mutant protein for GDP and GTP are essentially the same as those of the wild-type G domain, His84 is apparently not involved in the binding of the substrates. Calculations of the change in free energy of activation of the GTPase reaction following substitution of His84 by Gly point to the disruption of a weak hydrogen bond, involved in the catalytic reaction. This probably concerns an interaction via a water molecule. The possible mechanism underlying the GTPase reaction is discussed in light of the three-dimensional structure of EF-Tu, taking into account the situation of Ha ras p21. PMID- 1899021 TI - Grafting of a calcium-binding loop of thermolysin to Bacillus subtilis neutral protease. AB - The surface loop which in the Bacillus subtilis neutral protease (NP) extends from amino acid residue 188 to residue 194 was replaced, by site-directed mutagenesis, with the 10-residue segment which in the homologous polypeptide chain of thermolysin (TLN) binds calcium-4 [Matthews, B. W., Weaver, L. H., & Kester, W. R. (1974) J. Biol. Chem. 249, 8030-8044]. The mutant NP was isolated to homogeneity, and its structural, functional, calcium-binding, and stability properties were investigated. Proteolytic fragmentation with Staphylococcus aureus V8 protease of mutant NP was used to isolate and analyze the protein fragment encompassing the site of mutation, unambiguously establishing the effective insertion of the new 10-residue segment. Atomic absorption measurements allowed us to demonstrate that mutant NP binds three calcium ions instead of the two ions bound to wild-type NP, showing that indeed the chain segment grafted from TLN to NP maintains its calcium-binding properties. The mutant NP showed kinetic parameters essentially similar to those of the wild-type NP with Z-Phe Leu-Ala-OH as substrate. The enzyme inactivation of mutant vs wild-type NP was studied as a function of free [Ca2+]. It was found that mutant NP was much less stable than the wild-type NP when enzyme solutions were dialyzed at neutral pH in the presence of [Ca2+] below 10(-3) M. On the other hand, the kinetic thermal stability to irreversible inactivation of mutant NP, when measured in the presence of 0.1 M CaCl2, was found to be increased about 2-fold over that of the wild-type NP. Thus, modulation of enzyme stability by free [Ca2+] in mutant NP correlates with similar findings previously reported for thermolysin. Overall, the results obtained indicate that protein engineering experiments can be used to prepare hybrid proteins on the basis of sequence and function analysis of homologous protein molecules and show the feasibility of engineering metal ion binding sites into proteins. PMID- 1899023 TI - Novel type-specific lipooligosaccharides from Mycobacterium tuberculosis. AB - Mycobacterium tuberculosis (strain Canetti) is characterized by the presence of two novel glycolipids of the alkali-labile, trehalose-containing lipooligosaccharide class. Their structures were established by permethylation, partial acid hydrolysis, infrared and high-field NMR spectroscopy, and electron impact and fast atom bombardment mass spectrometry of the native glycolipids and hydrolysis products. The trehalose substituent is unique in that it is methylated at the 6'-position. The structure of the simpler of the two glycolipids is 2-O-Me alpha-L-Fucp(1----3)-beta-D-Glcp(1----3)-2-O-Me- alpha-L-Rhap(1----3)-2-O-Me alpha-L- Rhap(1----3)-beta-D-Glcp(1----3)-4-O-Me-alpha-L-Rhap(1----3) -6-O-Me alpha-D- Glc. Further glycosylation of the octaglycosyl unit of this nonantigenic glycolipid by an incompletely defined N-acyl derivative of a 4-amino-4,6-dideoxy Galp residue results in the second, highly antigenic nonasaccharide-containing glycolipid. Application of two-dimensional proton correlation spectroscopy demonstrated that the fatty acyl substituents are located on the 2,3,6 and 3,4,6 hydroxyl groups of the terminal glucosyl unit in the proportions of 2:3. Gas chromatography/mass spectrometry and optical rotation measurement allowed identification of the fatty acyl esters as primarily 2L-, 4L dimethylhexadecanoate, 2L-,4L-,6L-,8L-tetramethyloctadecanoate, and 2-methyl-3 hydroxyeicosanoate. The relationship of these glycolipids to different morphological forms of M. tuberculosis and to virulence is discussed. PMID- 1899024 TI - Actin and tubulin binding domains of synapsins Ia and Ib. AB - Synapsins Ia and Ib are neuronal phosphoproteins involved with the regulated clustering of small synaptic vesicles at the presynaptic terminus. In vitro they bind and bundle filaments of both actin and tubulin. Previously, we identified an actin binding domain in the NH2-terminal 25-kDa fragment (N25) generated by 2 nitro-5-thiocyanobenzoic acid (NTCB) cleavage of synapsin I and found that a complementary COOH-terminal 52-kDa portion of the molecule (N52) contained either a second actin binding site or a site of self-association [Petrucci, T. P., & Morrow, J. S. (1987) J. Cell. Biol. 105, 1355]. Using direct binding assays between actin, tubulin, and specific synapsin NTCB-derived peptides, we confirm the ability of purified N25 to bind but not bundle actin and demonstrate that the complementary N52 (or N50) fragments from synapsins Ia and Ib and a 14-kDa fragment derived from the middle of the molecule also associate directly with actin. An antibody specific for N25 inhibits the actin binding activity of N25 and the actin bundling but not the actin binding activity of intact synapsin I. Similar studies conducted with purified tubulin and tubulin immobilized on Sepharose demonstrate that both tubulin and actin bind at approximately the same sites in the NH2-terminal half of synapsin I. Although the fragments derived from the COOH terminus of both synapsin Ia and synapsin Ib (N40b/N34) were devoid of measurable actin binding activity after NTCB cleavage, they were specifically labeled in the intact molecule by a photoactivated cross-linker bound to F-actin. Collectively, these results indicate that synapsins Ia and Ib possess two actin and tubulin binding domains located in the NH2-terminal half of the molecule and suggest that a third actin binding domain is located in the COOH-terminal region. The NH2-terminal sites are found in NTCB peptides N25 and N14, while the third site, apparently of lower affinity, resides in N40b/N34. It is hypothesized that, in the intact molecule, the two NH2-terminal domains contribute to a single high affinity actin and/or tubulin binding site in the "globular" head region of synapsin I, while the third actin binding domain constitutes the topographically distinct site required for the actin bundling activity of the native molecule. The 45-residue COOH extension that distinguishes synapsin Ia from synapsin Ib appears not to be involved with actin binding, since no differences were found in the ability of N40b and N34 to be photo-cross-linked to actin.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1899025 TI - Deletion mutagenesis in Synechocystis sp. PCC6803 indicates that the Mn stabilizing protein of photosystem II is not essential for O2 evolution. AB - The photosystem II (PSII) reaction center complex coordinates a cluster of Mn atoms that are involved in the accumulation of oxidizing equivalents generated by light-induced charge separations within the intrinsic portion of the PSII complex. A 33-kDa extrinsic protein, termed the Mn-stabilizing protein (MSP), has been implicated in the stabilization of two of the four Mn atoms of the cluster, yet the precise role of this protein in O2 evolution remains to be elucidated. Here we describe the construction of a mutant of the cyanobacterium Synechocystis sp. PCC6803 in which the entire gene encoding MSP has been deleted. Northern and immunoblot analyses indicate that other PSII proteins are expressed and accumulated, despite the absence of MSP. Fluorescence emission spectra at 77 K indicate PSII assembles in the mutant, but that the binding of MSP is required for the normal fluorescence characteristics of the PSII complex, and suggest a specific interaction between MSP and CP47. Fluorescence induction measurements indicate a reduced rate of forward electron transport to the primary electron donor, P680, in the mutant. It is concluded that in contrast to previous reports, MSP is not required for the assembly of active PSII complexes nor is it essential for H2O-splitting activity in vivo. PMID- 1899026 TI - Identification of a membrane-bound, glycol-stimulated phospholipase A2 located in the secretory granules of the adrenal medulla. AB - Chromaffin granule membranes prepared from bovine adrenal medullae showed Ca2(+) stimulated phospholipase A2 (PLA2) activity when assayed at pH 9.0 with phosphatidylcholine containing an [14C]-arachidonyl group in the 2-position. However, the activity occurred in both soluble and particulate subcellular fractions, and did not codistribute with markers for the secretory granule. PLA2 activity in the granule membrane preparation was stimulated dramatically by addition of glycerol, ethylene glycol, or poly(ethylene glycol). This glycol stimulated PLA2 activity codistributed with membrane-bound dopamine beta hydroxylase, a marker for the granule membranes, through the sequence of differential centrifugation steps employed to prepare the granule membrane fraction, as well as on a sucrose density gradient which resolved the granules from mitochondria, lysosomes, and plasma membrane. The glycol-stimulated PLA2 of the chromaffin granule was membrane-bound, exhibited a pH optimum of 7.8, retained activity in the presence of EDTA, and was inactivated by p-bromophenacyl bromide. When different 14C-labeled phospholipids were incorporated into diarachidonylphosphatidylcholine liposomes, 1-palmitoyl-2 arachidonylphosphatidylcholine was a better substrate for this enzyme than 1 palmitoyl-2-oleylphosphatidylcholine or 1-acyl-2-arachidonyl phosphatidylethanolamine, and distearoylphosphatidylcholine was not hydrolyzed. PMID- 1899027 TI - Reciprocal communication between the lyase and synthase active sites of the tryptophan synthase bienzyme complex. AB - It is important to understand how the cleavage of indoleglycerol phosphate, which is catalyzed by the alpha subunits in the alpha 2 beta 2 bienzyme complex of tryptophan synthase, is modulated by the presence of L-serine in the beta subunits. Steady-state kinetic data, including the dependence of kcat on pH, allowed values to be assigned to each of the eight rate constants of the minimal catalytic mechanism. An ionizing group having an apparent pK value near 7.5 must be protonated for activity. The alpha active site ligands indolepropanol phosphate, glyceraldehyde 3-phosphate, and glycerol 3-phosphate increase both the affinity and the molar absorbance of L-serine and L-tryptophan bound to the beta active site. These effects prove that the alpha sites communicate with the beta sites over a distance of 30 A. 6-Nitroindole readily condenses with glyceraldehyde 3-phosphate, but not with L-serine. The turnover numbers for 6 nitroindoleglycerol phosphate and 6-nitroindole increased about 10-fold in both directions in the presence of L-serine bound to the beta 2 subunits. These data prove that the alpha and beta active sites communicate reciprocally and explain why the turnover number for the physiological reaction of indoleglycerol phosphate with L-serine greatly exceeds that of the cleavage reaction of indoleglycerol phosphate. PMID- 1899028 TI - Mechanism of the physiological reaction catalyzed by tryptophan synthase from Escherichia coli. AB - The physiological synthesis of L-tryptophan from indoleglycerol phosphate and L serine catalyzed by the alpha 2 beta 2 bienzyme complex of tryptophan synthase requires spatial and dynamic cooperation between the two distant alpha and beta active sites. The carbanion of the adduct of L-tryptophan to pyridoxal phosphate accumulated during the steady state of the catalyzed reaction. Moreover, it was formed transiently and without a lag in single turnovers, and glyceraldehyde 3 phosphate was released only after formation of the carbanion. These and further data prove first that the affinity for indoleglycerol phosphate and its cleavage to indole in the alpha subunit are enhanced substantially by aminoacrylate bound to the beta subunit. This indirect activation explains why the turnover number of the physiological reaction is larger than that of the indoleglycerol phosphate cleavage reaction. Second, reprotonation of nascent tryptophan carbanion is rate limiting for overall tryptophan synthesis. Third, most of the indole generated in the active site of the alpha subunit is transferred directly to the active site of the beta subunit and only insignificant amounts pass through the solvent. Comparison of the single turnover rate constants with the known elementary rate constants of the partial reactions catalyzed by the alpha and beta active sites suggests that the cleavage reaction rather than the transfer of indole or its condensation with aminoacrylate is rate limiting for the formation of nascent tryptophan. PMID- 1899029 TI - Quantitative analysis of the contribution of Glu46 and Asn98 to the guanosine specificity of ribonuclease T1. AB - In the crystal structure of the ribonuclease T1 (RNase T1; EC 3.1.27.3)-2'-GMP complex the hydrogen-bonding potential of the guanine base is saturated [Arni, R., Heinemann, U., Tokuoka, R., & Saenger, W. (1988) J. Biol. Chem. 263, 15358 15368]. The oxygens of the Glu46 carboxylate and the Asn98 main-chain carbonyl act as hydrogen-bond acceptors for the N(1)H-C(2)-N(2)H2 part of the base. We measured the transesterification kinetics of wild-type and Glu46Ala RNase T1 using the GpU, IpU, and XpU series of analogous substrates. We found that the N(1)H---Glu46 O epsilon 1, the N(2)H---Glu46 O epsilon 2, and the N(2)H---Asn98 O hydrogen bonds have an apparent contribution of 2.7, 1.1, and 1.2 kcal/mol to the interaction energy of the enzyme and the transition state of the substrate. Wild type RNase T1 discriminates guanine from nonionized xanthine (a guanine analogue in which the exocyclic amino group is replaced by an oxygen) by about 4.4 kcal/mol. Loss of the specific hydrogen bonds with the exocyclic amino group of the guanine base accounts for 2.4 kcal/mol of this discrimination energy; 2.0 kcal/mol is due to unfavorable non-H-bonded oxygen-oxygen contacts in the enzyme xanthine complex. A pH dependence study shows that the deprotonated form of xanthine (i.e., the 6-keto-2-enolate anion; pKa = 5.4) is far less preferred, if not excluded, as substrate by wild-type RNase T1; this may be attributed to an electrostatic repulsion of the negatively charged xanthine by the Glu46 carboxylate group. PMID- 1899030 TI - Human secreted carbonic anhydrase: cDNA cloning, nucleotide sequence, and hybridization histochemistry. AB - Complementary DNA clones coding for the human secreted carbonic anhydrase isozyme (CA VI) have been isolated and their nucleotide sequences determined. These clones identify a 1.45-kb mRNA that is present in high levels in parotid submandibular salivary glands but absent in other tissues such as the sublingual gland, kidney, liver, and prostate gland. Hybridization histochemistry of human salivary glands shows mRNA for CA VI located in the acinar cells of these glands. The cDNA clones encode a protein of 308 amino acids that includes a 17 amino acid leader sequence typical of secreted proteins. The mature protein has 291 amino acids compared to 259 or 260 for the cytoplasmic isozymes, with most of the extra amino acids present as a carboxyl terminal extension. In comparison, sheep CA VI has a 45 amino acid extension [Fernley, R. T., Wright, R. D., & Coghlan, J. P. (1988b) Biochemistry 27, 2815]. Overall the human CA VI protein has a sequence identity of 35% with human CA II, while residues involved in the active site of the enzymes have been conserved. The human sheep secreted carbonic anhydrases have a sequence identity of 72%. This includes the two cysteine residues that are known to be involved in an intramolecular disulfide bond in the sheep CA VI. The enzyme is known to be glycosylated and three potential N-glycosylation sites (Asn X-Thr/Ser) have been identified. Two of these are known to be glycosylated in sheep CA VI. Southern analysis of human DNA indicates that there is only one gene coding for CA VI. PMID- 1899031 TI - Oligosaccharide structures present on asparagine-289 of recombinant human plasminogen expressed in a Chinese hamster ovary cell line. AB - The oligosaccharide structures linked to Asn289 of a recombinant (r) variant (R561S) human plasminogen (HPg) expressed in Chinese hamster ovary (CHO) cells, after transfection of these cells with a plasmid containing the cDNA coding for the variant HPg, have been determined. Employing high-performance anion-exchange liquid chromatography mapping of the oligosaccharide units cleaved from the protein by glycopeptidase F, compared with elution positions of standard oligosaccharides, coupled with monosaccharide compositional determinations and analyses of sequential exoglycosidase digestions and specific lectin binding, we find that considerable microheterogeneity in oligosaccharide structure exists at this sole potential N-linked glycosylation site on HPg. A variety of high-mannose structures, as well as bi-, tri-, and tetraantennary complex-type carbohydrate, has been found, in relative amounts of 1-25% of the total oligosaccharides. The complex-type structures contain variable amounts of sialic acid (Sia), ranging from 0 to 5 mol/mol of oligosaccharide in the different glycan structures. Neither hybrid-type molecules, N-acetylglucosamine bisecting oligosaccharides, nor N-acetyllactosaminyl-repeat structures were found to be present in the complex-type carbohydrate pool in observable amounts. Of interest, a significant portion of the Sia exists an outer arm structures in an (alpha 2,6) linkage to the penultimate galactose, a novel finding in CHO cell-directed glycosylation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1899032 TI - Use of photoaffinity probes containing poly(ethylene glycol) spacers for topographical mapping of the cholecystokinin receptor complex. AB - To further define the structure of the pancreatic cholecystokinin (CCK) receptor and the topographical distance relationships between its subunits, we developed a series of monofunctional photoaffinity probes in which a fixed receptor-binding domain was separated from a photolabile nitrophenylacetamido group by defined lengths of a flexible spacer. The well-characterized CCK receptor radioligand 125I-D-Tyr-Gly-[(Nle28,31)CCK-26-33] provided the receptor-binding component of the probes, while the polymer poly(ethylene glycol) (2, 4, 7, and 10 monomer units long) was used as the spacer. The patterns of affinity labeling of rat pancreatic plasma membranes were examined as a function of spacer length. This ranged from 7.3 to 16.2 A, as calculated by root-mean-square end-to-end distances and validated experimentally by time-resolved fluorescence resonance energy transfer measurements. All probes in the series specifically labeled the Mr = 85,000-95,000 glycoprotein with Mr = 42,000 core, which has been proposed to contain the hormone recognition site. In addition, when the spacer length reached 16.2 A, membrane proteins of Mr = 80,000 and Mr = 40,000 were specifically labeled. The product of endo-beta-N-acetylglucosaminidase F digestion of the Mr = 80,000 protein was Mr = 65,000, similar to a protein previously identified in affinity labeling experiments using a CCK-33-based probe. These observations are consistent with the Mr = 85,000-95,000 pancreatic protein representing the hormone-binding subunit of the CCK receptor, while proteins of Mr = 80,000 and Mr = 40,000 may represent noncovalently associated subunits sited within 16.2 A of the binding domain.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1899033 TI - Laser flash photolysis studies of the reduction kinetics of NADPH:cytochrome P 450 reductase. AB - The reduction kinetics of NADPH:cytochrome P-450 reductase have been investigated by the laser flash photolysis technique, using the semiquinone of 5 deazariboflavin (5-dRfH.) as the reductant. Transients observed at 470 nm at neutral pH indicated that the oxidized reductase was reduced via second-order kinetics with a rate constant of 6.8 X 10(7) M-1 s-1. The second-order rate constant corresponding to the formation of the protein-bound semiquinone (measured at 585 nm) was essentially the same as that obtained at 470 nm (7.1 X 10(7) M-1 s-1). Subsequent to this rapid formation of protein-bound semiquinone, a partial exponential decay was observed at 585 nm. The rate of this decay remained invariant with protein concentration between pH 5.0 and 7.0, and a first order rate constant of 70 s-1 was obtained for this process. This is assigned to intramolecular electron transfer from FADH. to FMN. Prior reduction of the enzyme to the one-electron level led to a decrease in both the second-order rate constant for reduction (2 X 10(7) M-1 s-1) and the first-order intraflavin electron transfer rate constant (15 s-1). The protein-bound FAD moiety of FMN depleted reductase was reduced by 5-dRfH. with a second-order rate constant that was identical with that observed with the native enzyme (6.9 X 10(7) M-1 s-1). However, with this species no significant decay of the FAD semiquinone was observed at 585 nm following its rapid formation, consistent with the above assignment of this kinetic process.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1899034 TI - A mutant of DNA polymerase I (Klenow fragment) with reduced fidelity. AB - The kinetic parameters governing incorporation of correct and incorrect bases into synthetic DNA duplexes have been investigated for Escherichia coli DNA polymerase I [Klenow fragment (KF)] and for two mutants, Tyr766Ser and Tyr766Phe. Tyr766 is located at the C-terminus of helix O in the DNA-binding cleft of KF. The catalytic efficiency for correct incorporation of dNTP is reduced 5-fold for Tyr766Ser. The catalytic efficiencies of all 12 possible misincorporations have been determined for both KF and Tyr766Ser by using single-turnover kinetic conditions and a form of the enzyme that is devoid of the 3'-5' exonuclease activity because of other single amino acid replacements. Tyr766Ser displays an increased efficiency of misincorporation (a reduction in fidelity) for several of the 12 mismatches. The largest increase in efficiency of misincorporation for Tyr766Ser occurs for the misincorporation of TMP opposite template guanosine, a 44-fold increase. In contrast, the efficiencies of misincorporation of dAMP opposite template A, G, or C are little affected by the mutation. A determination of the kinetic parameters associated with a complete kinetic scheme has been made for Tyr766Ser. The rate of addition of the next correct nucleotide onto a preexisting mismatch is decreased for Tyr766Ser. The fidelity of Tyr766Phe was not substantially different from that of KF for the misincorporations examined, indicating that it is the loss of the phenolic ring of the side chain of Tyr766 that leads to the significant decrease in fidelity. The results indicate that KF actively participates in the reduction of misincorporations during the polymerization event and that Tyr766 plays an important role in maintaining the high fidelity of replication by KF. PMID- 1899035 TI - Three-dimensional structural analysis of the group B polysaccharide of Neisseria meningitidis 6275 by two-dimensional NMR: the polysaccharide is suggested to exist in helical conformations in solution. AB - The solution conformations of the group B polysaccharide of Neisseria meningitidis were analyzed by DQF-COSY and pure absorption 2D NOE NMR with three mixing times. The pyranose ring of the sialic acid residue was found to be in the 2C5 conformation. The DQF-COSY analysis indicated that the orientations of H6 and H7 and of H7 and H8 are both gauche. In order to overcome the difficulties in analyzing the NOE data due to the two sets of proton overlaps, molecular modeling of alpha-2,8-linked sialic acid oligomers was carried out to investigate possible conformers, and theoretical NOE calculations were performed by using CORMA (complete relaxation matrix analysis). Our analysis suggests that the polysaccharide adopts helical structures for which the phi (defined by O6-C2-O8 C8) and psi (C2-O8-C8-C7) angles are in the following ranges: phi -60 to 0 degrees, psi 115-175 degrees or phi 90-120 degrees, psi 55-175 degrees. The weak affinity of anti-B antibodies for smaller alpha-2,8-linked oligosaccharides may be due to the fact that such oligomers are more flexible and may not form an ordered structure as the poly(sialic acid) does. PMID- 1899036 TI - Effects of apolipoproteins on the kinetics of cholesterol exchange. AB - The effects of apolipoproteins on the kinetics of cholesterol exchange have been investigated by monitoring the transfer of [14C]cholesterol from donor phospholipid/cholesterol complexes containing human apolipoproteins A, B, or C. Negatively charged discoidal and vesicular particles containing purified apolipoproteins complexed with lipid (75 mol % egg PC, 15 mol % dicetyl phosphate, and 10 mol % cholesterol) and a trace of [14C]cholesterol were incubated with a 10-fold excess of neural, acceptor, small unilamellar vesicles (SUV; 90 mol % egg PC and 10 mol % cholesterol). The donor and acceptor particles were separated by chromatography on DEAE-Sepharose, and the rate of movement of labeled cholesterol was analyzed as a first-order exchange process. The kinetics of exchange of cholesterol from both vesicular and discoidal complexes that contain apoproteins are consistent with an aqueous diffusion mechanism, as has been established previously for PC/cholesterol SUV. The addition of 2-3 molecules of apo A-I to a donor SUV does not significantly alter the half-time (t1/2), which is 80 +/- 9 min at 37 degrees C. However, addition of 5-12 apo A-I molecules progressively decreases t1/2 from 65 +/- 2 to 45 +/- 4 min. This enhancement in the rate of desorption of cholesterol molecules is presumed to arise from the creation of packing defects at boundaries around the apoprotein molecules, which are intercalated among the phospholipid and cholesterol molecules in the surface of the donor SUV.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1899038 TI - Isolation of two chloroethylnitrosourea-sensitive Chinese hamster cell lines. AB - 1-[(4-Amino-2-methylpyrimidin-5-yl)methyl]-3-(2-chloroethyl)-3- nitrosourea hydrochloride (ACNU), a cancer chemotherapeutic bifunctional alkylating agent, causes chloroethylation of DNA and subsequent DNA strand cross-linking through an ethylene bridge. We isolated and characterized two ACNU-sensitive mutants from mutagenized Chinese hamster ovary cells and found them to be new drug-sensitive recessive Chinese hamster mutants. Both mutants were sensitive to various monofunctional alkylating agents in a way similar to that of the parental cell lines CHO9. One mutant (UVS1) was cross-sensitive to UV and complemented the UV sensitivity of all Chinese hamster cell lines of 7 established complementation groups. Since UV-induced unscheduled DNA synthesis was very low, a new locus related to excision repair is thought to be defective in this cell line. Another ACNU-sensitive mutant, CNU1, was slightly more sensitive to UV than the parent cell line. CNU1 was cross-sensitive to 1-(2-chloroethyl)-3-cyclohexyl-1 nitrosourea and slightly more sensitive to mitomycin C. No increased accumulation of ACNU and a low level of UV-induced unscheduled DNA synthesis in this cell as compared with the parental cell line suggest that there is abnormality in a repair response of this mutant cell to some types of DNA cross-links. PMID- 1899037 TI - Programmed cell death during regression of the MCF-7 human breast cancer following estrogen ablation. AB - To study the mechanism of regression of human mammary cancer following estrogen ablation, estrogen-responsive MCF-7 human mammary adenocarcinoma cells were inoculated into ovariectomized female nude mice supplemented with exogenous 17 beta-estradiol (E2) via an E2 implant. Implants were then removed when MCF-7 tumors were 400 mm3 in size. Removal of the E2 implants resulted in a 50% tumor regression by 2 weeks following E2 ablation. Associated with this regression is a rapid (i.e., within 1 day following E2 ablation) enhanced expression of the transforming growth factor beta 1 and TRPM-2-genes, two genes the expression of which has been previously demonstrated to be enhanced in a variety of cell types induced to undergo programmed cell death (i.e., apoptosis). The enhanced expression of transforming growth factor beta 1 and TRPM-2 is not a nonspecific response since the expression of other genes, like c-fos, c-H-ras, and pS2, decrease following E2 ablation. Fragmentation of tumor DNA into nucleosomal oligomers and histological appearance of apoptotic bodies are characteristic early events that precede the dramatic reduction in tumor volume following E2 ablation. These results demonstrate that the regression of MCF-7 human mammary cancers in nude mice following estrogen ablation is due to a sequence of biochemical and morphological changes that result in both the cessation of cell proliferation and activation of programmed death or apoptosis of these MCF-7 cancer cells. Clarification of the biochemical pathway involved in the activation of this programmed cell death should identify new targets of therapy for even estrogen-independent human mammary cancer cells. PMID- 1899039 TI - Combination effect of recombinant human interleukin 1 alpha with antitumor drugs on syngeneic tumors in mice. AB - To investigate the combination effects of recombinant human interleukin 1 alpha (rHu IL-1 alpha) and antitumor drugs, groups of 7 mice bearing syngeneic tumors (Meth A sarcoma in BALB/c mice and colon 26 adenocarcinoma in BALB/c x DBA/2 F1 mice) were treated i.v. with the antitumor drugs according to the early (once daily on days 1, 4, 7, 10, and 13) and/or late (once daily on days 7, 10, 13, 16, and 19) medication schedules in combination with rHu IL-1 alpha administered i.m. at various timings (1 day before, concurrently with, and 1 day after every drug administration). Inhibition rates of the antitumor drugs (mitomycin C, doxorubicin, cisplatin, cyclophosphamide, and 5-fluorouracil) for both the murine tumors were more or less raised by coadministration of rHu IL-1 alpha irrespective of medication schedules and combination timings. After both early and late treatments with the optimal combinations of rHu IL-1 alpha (0.1-3 micrograms/mouse) and cisplatin (2-4 mg/kg) and by the late treatment with the optimal combinations of rHu IL-1 alpha (0.3-3 micrograms/mouse) and carboplatin (32 mg/kg) or thiotepa (4 mg/kg), many mice were completely cured of colon 26 adenocarcinoma and survived for more than 90 days. Combined use of rHu IL-1 alpha and antitumor drugs seems to be beneficial in antitumor chemotherapy. PMID- 1899040 TI - Preclinical study of sequential tumor necrosis factor and interleukin 2 in the treatment of spontaneous canine neoplasms. AB - Recombinant human tumor necrosis factor and recombinant human interleukin 2 were administered in a sequential schedule to 30 dogs with a variety of spontaneous neoplasms. Dose escalation of both drugs was performed, and a maximally tolerated dose of recombinant human tumor necrosis factor of 125 mg/m2 i.v. for 3 days, followed by 1.5 x 10(6) units/m2 of recombinant human interleukin 2 s.c. for 9 days, was derived. Dose-limiting toxicities were primarily gastrointestinal; however, weakness and malaise were seen during therapy at doses higher than the maximally tolerated dose. No clinically significant hematological toxicities were seen at any dose level. Objective tumor responses were seen in dogs with oral mucosal melanoma and cutaneous mastocytoma. Because of the histological, behavioral, and epidemiological similarities between human and canine tumor types, the canine cancer patient provides a unique model for the preclinical evaluation of recombinant cytokine therapy. PMID- 1899041 TI - Direct in vitro lysis of metastatic tumor cells by cytokine-activated murine vascular endothelial cells. AB - The purpose of these studies was to determine whether vascular endothelial cells can be treated with various cytokines to become cytotoxic against tumorigenic target cells under defined conditions in vitro. Microvascular endothelial cells were isolated from immunocompetent mice by perfusion of lungs grown in culture, cloned, and then characterized. The cloned microvascular endothelial cells were activated by incubation with a combination of recombinant tumor necrosis factor alpha and recombinant-gamma interferon (10 units/ml each) for 24 h. Activated endothelial but not control endothelial cells (incubated in medium alone, recombinant tumor necrosis factor alpha alone, or recombinant gamma interferon alone) produced significant lysis of mouse reticulum cell sarcoma and two different mouse melanomas. Moreover, at the concentrations used here, recombinant tumor necrosis factor alpha and recombinant gamma interferon did not produce direct target cell lysis. The activated endothelial cell-mediated tumor cell lysis depended on the continuous presence of the cytokines and was not due solely to initial target cell binding. The results demonstrate that, like macrophages, microvessel endothelial cells exposed to low levels of cytokines are capable of lysing tumor cells. PMID- 1899042 TI - Expression of class I major histocompatibility complex antigens in Epstein-Barr virus-carrying lymphoblastoid cell lines and Burkitt lymphoma cells. AB - Epstein-Barr virus (EBV) carrying lymphoblastoid cell lines (LCLs) and EBV positive Burkitt lymphoma (BL) cells were compared for their expression of class I antigens of the major histocompatibility complex. Five common BL lines, LCLs, pokeweed mitogen-stimulated blasts and resting B-cells from healthy donors, and eight pairs of BL cells and LCLs, each pair originating from one patient, were tested. Quantitative analysis was performed using a radioimmunoassay; qualitative aspects were studied by one- and two-dimensional gel electrophoresis. In general, LCLs expressed significantly higher amounts of class I antigens than BL cells, the latter showing class I densities similar to or lower than peripheral resting B-cells. From analysis of the expression of class I-specific RNA, there is some evidence that class I antigen expression is regulated on the transcriptional level. In two BL cells studied, class I expression could be enhanced by gamma interferon, whereas the corresponding LCLs seemed to be refractory to this treatment. One- and two-dimensional gel electrophoresis showed that in some BL lines, in addition to the generally lower class I expression, distinct class I specificities were down-regulated. None of these alterations in class I expression was EBV specific; however, they may well play a role in the recognition of BL cells and LCLs by cellular immune mechanisms. Thus, down regulation of class I antigens may contribute to the resistance of BL cells to cytotoxic T-lymphocytes, whereas their enhanced expression may improve the recognition of EBV-infected LCLs. PMID- 1899043 TI - Early lesion of N-nitroso-N-ethylurea-induced hamster neurofibromatosis model. AB - To investigate histogenesis of neurofibroma, early lesions of N-nitroso-N ethylurea-induced neurofibroma of Syrian golden hamsters were examined. The lesions were detectable from 8 weeks of age, and a total of 14 lesions in 9 hamsters from 8 to 12 weeks of age were observed. Most of the lesions were found in the skin; they were also observed in the trigeminal nerve, cervical plexus, and abdominal sympathetic ganglion. Histological examination revealed there were two types of early lesions such as solitary and plexiform types. The former developed in the s.c. or dermal part of the skin and showed invasive growth of the surrounding tissue, while the latter originated from the large nerves such as the trigeminal nerve or cervical plexus. Growth kinetics of the early lesions was quantitated by continuous administration of bromodeoxyuridine and double immunostaining. Using these systems we observed that various kinds of cells had already participated in early lesions and later Schwann cells became a main component of the tumor. The histogenesis of neurofibroma was considered to be complexed by proliferation of several kinds of cell types at the early stage. PMID- 1899044 TI - Promoter independence as a feature of most skin papillomas in SENCAR mice. AB - In the present study, the fate of individual papillomas induced by initiation promotion on the backs of SENCAR mice was monitored after discontinuation of limited promoter treatment. Groups of 40 SENCAR mice each were initiated by a single topical application of 7,12-dimethylbenz[a]anthracene (DMBA) at 2, 1, 0.5, or 0.25 micrograms/mouse. Animals were promoted with 2 micrograms of 12-O tetradecanoylphorbol-13-acetate (TPA) twice weekly during 10 weeks. At that time point, 10 papilloma bearing mice from each group were randomly selected to follow the growth of their existing tumors. Animals and their individual tumors were identified, charted, and photographed weekly. After an initial increase, the average number of papillomas/mouse remained constant after discontinuation of TPA in all the groups except the group receiving the highest DMBA dose (Group 1) and with highest tumor load. Twenty-one weeks after TPA was discontinued, only 10-20% of the papillomas had regressed and no statistically significant differences were found among the different DMBA dose groups. On the other hand, Group 1 showed the highest percentage of coalescing tumors which was apparently a function of tumor load. In addition, no differences were observed in the proportion of positive tumors with activating point mutations at codon 61 of the Ha-ras gene when comparing samples of papillomas from the highest DMBA initiation dose group (2 micrograms) versus the lowest DMBA initiation dose group (0.25 micrograms). Our present data suggest that papillomas induced with low doses of DMBA in SENCAR mice are no more TPA dependent than those induced by higher initiating doses. Furthermore, in SENCAR mice at the doses used in the present study (0.25-2 micrograms/mouse), the number of so-called "promoter dependent" papillomas represents only a small percentage of the total papillomas produced using the initiation-promotion protocol. PMID- 1899045 TI - Heterogeneous repair of methylnitrosourea-induced alkali-labile sites in different DNA sequences. AB - The repair of DNA damage induced by methylnitrosourea (MNU) in restriction fragments containing the dihydrofolate reductase (DHFR) gene in Chinese hamster ovary cells was compared to that in equal size restriction fragments containing a nontranscribed flanking sequence 3' to the DHFR gene or the c-fos gene. Following exposure to 10(-3) M MNU, restriction fragments containing either the DHFR gene or the 3' flanking sequence had similar amounts of alkali labile sites, approximately 2 sites/restriction fragment. Fragments encompassing the c-fos gene had less than 2 breaks/fragment. Twenty-four h after exposure to MNU a consistent, but slight and not statistically significant, difference was seen with more adducts removed from the DHFR gene than the 3' flanking sequence. No repair was detected in the c-fos containing fragments. In addition, the repair of N7-methylguanine in the overall genome was assessed by use of a 32P end-labeling technique. Seventy % of this major alkylation product was repaired after 24 h. These findings establish that repair heterogeneity occurs in Chinese hamster ovary cells after exposure to MNU. PMID- 1899046 TI - Inhibitory effects of curcumin on in vitro lipoxygenase and cyclooxygenase activities in mouse epidermis. AB - Topical application of curcumin, the yellow pigment in turmeric and curry, strongly inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced ornithine decarboxylase activity, DNA synthesis, and tumor promotion in mouse skin (Huang et al., Cancer Res., 48: 5941-5946, 1988). Chlorogenic acid, caffeic acid, and ferulic acid (structurally related dietary compounds) were considerably less active. In the present study, topical application of curcumin markedly inhibited TPA- and arachidonic acid-induced epidermal inflammation (ear edema) in mice, but chlorogenic acid, caffeic acid, and ferulic acid were only weakly active or inactive. The in vitro addition of 3, 10, 30, or 100 microM curcumin to cytosol from homogenates of mouse epidermis inhibited the metabolism of arachidonic acid to 5-hydroxyeicosatetraenoic acid (5-HETE) by 40, 60, 66, or 83%, respectively, and the metabolism of arachidonic acid to 8-HETE was inhibited by 40, 51, 77, or 85%, respectively [IC50 (concentration needed for 50% inhibition) = 5-10 microM]. Chlorogenic acid, caffeic acid, or ferulic acid (100 microM) inhibited the metabolism of arachidonic acid to 5-HETE by 36, 10, or 16%, respectively, and these hydroxylated cinnamic acid derivatives inhibited the metabolism of arachidonic acid to 8-HETE by 37, 20, or 10%, respectively (IC50 greater than 100 microM). The metabolism of arachidonic acid to prostaglandin E2, prostaglandin F2 alpha, and prostaglandin D2 by epidermal microsomes was inhibited approximately 50% by the in vitro addition of 5-10 microM curcumin. Chlorogenic acid, caffeic acid, and ferulic acid (100 microM) were inactive. In vitro rat brain protein kinase C activity was not affected by 50-200 microM curcumin, chlorogenic acid, caffeic acid, or ferulic acid. The inhibitory effects of curcumin, chlorogenic acid, caffeic acid, and ferulic acid on TPA-induced tumor promotion in mouse epidermis parallel their inhibitory effects on TPA-induced epidermal inflammation and epidermal lipoxygenase and cyclooxygenase activities. PMID- 1899047 TI - 4 Beta- and 4 alpha-12-O-tetradecanoylphorbol-13-acetate elicit arachidonate release from epidermal cells through different mechanisms. AB - There is substantial evidence that the tumor promoter 4 beta-12-O tetradecanoylphorbol-13-acetate (TPA) elicits enhanced arachidonic acid release and its metabolism to prostaglandins and lipoxygenase products in many cell types. The goal of this study was to determine whether 4 alpha-12-O tetradecanoylphorbol-13-acetate (4 alpha TPA), a stereoisomer of TPA, can induce arachidonic acid release and whether it is by the same mechanism as release induced by TPA. The finding that 10 micrograms/ml 4 alpha TPA produces a response comparable with 1 microgram/ml TPA and with similar kinetics was unexpected. The mechanism mediating the TPA response appears to be the activation of protein kinase C (PKC), which subsequently results in phospholipase A2 activation. This is suggested by the observation that TPA-induced arachidonate release is inhibited 65% by 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H 7), an inhibitor of PKC and that TPA completely down-regulates PKC. In addition, down-regulation or depletion of PKC by prior treatment with TPA results in a 75% loss of response to a second TPA treatment. In vitro activation of partially purified PKC could be demonstrated for TPA but not 4 alpha TPA. 4 alpha TPA thus appears to induce the release of arachidonate by a different but unknown mechanism. The 4 alpha TPA effect is not significantly reduced by the PKC inhibitor H-7, and no evidence of PKC activation or down-regulation was observed. Additionally, 4 alpha TPA is unable to "down-regulate" arachidonate release when the two-treatment protocol is used and the down-regulation of PKC by TPA has little effect on 4 alpha TPA-induced arachidonate release. Cycloheximide inhibited TPA-induced arachidonate release by 80% and 4 alpha TPA-induced release by 50%, indicating a partial requirement for protein synthesis for both phorbol esters. Actinomycin D, on the other hand, inhibited the TPA response by 70%, but enhanced the 4 alpha TPA response by 169%. When used at 10- or 100-micrograms doses, 4 alpha TPA was found to lack activity with respect to ornithine decarboxylase induction, oxidant production, hyperplasia, inflammation, and tumor promotion, suggesting that arachidonate release is not sufficient to induce these events. This may be related to the observation that with TPA the extent of arachidonate metabolism to prostaglandin E2 is four- to fivefold greater than occurred with 4 alpha TPA, even under conditions of equivalent arachidonate release. PMID- 1899048 TI - Effects of type of dietary fat on phorbol ester-elicited tumor promotion and other events in mouse skin. AB - Based on the biological activity of arachidonic acid metabolites, we hypothesized that alterations in the consumption of linoleic acid, the precursor to arachidonic acid, would result in a modification in tumor development when fed during the tumor promotion stage of the mouse skin initiation-promotion model. The effects of seven different levels of dietary linoleic acid (LA), supplied as corn oil in a 15% fat diet, on the incidence and rate of papilloma and carcinoma development were determined. SENCAR mice were placed on one of the experimental diets, containing 1.0, 3.6, 6.0, 7.9, 9.9, 12.5, or 15.0% corn oil, 1 week after initiation with 10 nmol of 7,12-dimethylbenz(a)anthracene and 3 weeks prior to the start of twice weekly promotion with 1 micrograms 12-O-tetradecanoylphorbol 13-acetate (TPA). At 15 weeks of TPA treatment there were significant differences in papilloma number among diet groups, such that an inverse correlation (r = 0.92) was observed between tumor number and level of corn oil; the lowest corn oil diet group had an average of 11.7 tumors/mouse, while the highest corn oil group had 5.4 tumors/mouse. However, there was little difference in tumor incidence among diet groups. A general relationship between diet and carcinoma incidence was also found, such that the highest corn oil diet group had the lowest carcinoma incidence. In an experiment performed with DBA/2 mice, the average number of papillomas/mouse at 17 weeks was 4.5 (1.0% corn oil), 5.6 (7.9%) corn oil), and 2.3 (15.0% corn oil). Papilloma incidence was also affected by diet, with a 79% incidence for the 15.0% corn oil and an incidence of 93% for the 1.0% corn oil group. analyses of the fatty acid composition of epidermal phospholipids in mice fed the experimental diets reflected the dietary LA levels, in that an accumulation of phospholipid LA, accompanied by an overall decrease in arachidonic acid, occurred with increasing dietary corn oil. In spite of the high membrane levels of LA, no measurable amount of epidermal conjugated dienes of LA could be detected. Epidermal prostaglandin E2 levels in acetone-treated mice were similar for all diet groups (approximately 3 pg/micrograms DNA). However, 6 h after topical application with 4 micrograms of TPA, prostaglandin E2 levels were elevated 5- to 10-fold; an inverse correlation (P less than 0.05) was seen with increasing dietary LA, although the concordance with decreased phospholipid arachidonic acid was not strong.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1899049 TI - Liposome-encapsulated antigens are processed in lysosomes, recycled, and presented to T cells. AB - Antigen processing requires intracellular antigen catabolism to generate immunogenic peptides that bind to class II MHC molecules (MHC-II) for presentation to T-cells. We now provide direct evidence that these peptides are produced within dense lysosomes, as opposed to earlier endocytic compartments. The protein antigen hen egg lysozyme was targeted to endosomes or lysosomes by encapsulating it in liposomes of different membrane composition. Acid-sensitive liposomes released their contents in early endosomes, whereas acid-resistant liposomes sequestered their contents from potential endosomal processing events and released their contents only after delivery to lysosomes. Antigen encapsulated in acid-resistant liposomes was processed in a chloroquine-sensitive manner and presented more efficiently than soluble antigen or antigen encapsulated in acid-sensitive liposomes. Thus, peptides may be recycled from lysosomes, transported to endosomes to bind MHC-II, and then expressed at the cell surface. PMID- 1899050 TI - The Drosophila gastrulation gene concertina encodes a G alpha-like protein. AB - Gastrulation is a complex process requiring the coordination of cell shape changes and cell movements. In Drosophila, gastrulation begins immediately upon cellularization of the blastoderm stage embryo with the formation of the ventral furrow and posterior midgut. Cells that form both of these invaginations change their shape via apical constriction. Embryos from mothers homozygous for mutations in the concertina (cta) gene begin furrow formation by forming a zone of tightly apposed cells, constrict some cells, and then fail to constrict enough cells to form an organized groove. The cta gene has been cloned, and sequence analysis suggests that it encodes an alpha subunit of a G protein. G proteins have a role in cell-cell communication as mediators of signals between membrane bound receptors and intracellular effectors. The phenotype of embryos from homozygous cta mothers suggests that the cta gene plays a role in a signal transduction pathway used during gastrulation. PMID- 1899051 TI - Establishment of murine macrophage-like mutant and hybrid cell lines: comparative analysis of the differentiation induced by 1 alpha,25-dihydroxyvitamin D3 and recombinant murine interferon-gamma. AB - The purpose of this study is to establish the monocyte/macrophage-like cell lines which are sensitive to potent systemic and local factors, 1 alpha,25 dihydroxyvitamin D3 (1 alpha,25(OH)2 VD3) and interferon-gamma (IFN-gamma). We established two variant mouse macrophage-like cell lines, whose responses to 1 alpha,25(OH)2 VD3 and IFN-gamma differed from one another. The AH-sensitive mutant cell line (G3) was induced by allowing P388D1 tolerant to 8-azaguanine. G3 mutant cells were then fused with the 1 alpha,25(OH)2 VD3-stimulated bone marrow cells isolated from DBA/2 mice. After AH selection the hybrid cell line (XC) was established. The G3 mutant cell line and the XC hybrid cell line had macrophage like characteristics, such as surface antigens, Fc receptor, C3 receptor, and lysosomal enzymes. The treatment of G3 mutant cells with 1 alpha,25(OH)2 VD3 inhibited cell proliferation with morphological changes, and increased acid phosphatase activity, phagocytic activity, and F4/80 antigen expression on the cell surface. In contrast, IFN-gamma inhibited cell proliferation without effect on acid phosphatase activity and phagocytic activity but increased F4/80 antigen expression. In XC hybrid cells, on the other hand, IFN-gamma, but not 1 alpha,25(OH)2 VD3, inhibited cell proliferation with morphological changes but increased phagocytic activity and F4/80 antigen expression. In addition, IFN gamma, but not 1 alpha,25(OH)2 VD3, dose-dependently increased multinucleated cell formation of both cells. These findings suggest that the G3 mutant cell line with macrophage-like characteristics is 1 alpha,25(OH)2 VD3- and IFN-gamma sensitive, and that the XC hybrid cell line is, despite its macrophage-like characteristics, only IFN-gamma-sensitive. Therefore, these newly established cell lines will provide useful systems in studying the differentiation of monocyte/macrophage lineage. PMID- 1899052 TI - Phenotypic and functional heterogeneity of thymic and splenic lymphokine activated killer cells relative to ornithine sensitivity. AB - We have previously reported the selective inhibition of cytotoxic T lymphocytes (CTL) by 10 mM ornithine (ORN) relative to natural killer (NK) cell-derived lymphokine activated killer cells (LAK). To determine if this were due to differences in the progenitor cells or the type of stimulus, we used cortisone resistant thymocytes (CRT) as a source of mature T cells for induction of LAK and CTL, and compared the results with spleen. Thymic and splenic CTL precursors (CTLp) from C57B1/6 (B6) mice were CD8+, ASGM1-, ORN sensitive. Splenic LAK precursors (LAKp) were CD8-, ASGM1+, ORN resistant when assayed against both YAC 1 and P815 tumor targets. In contrast, CRT-derived LAKp were CD8-, ASGM1+, ORN resistant against YAC-1, whereas LAKp against P815 were CD8+, ASGM1+, ORN sensitive. ORN sensitivity was also observed among CTL and LAK in DBA/2 mice and was associated with CD8+ phenotype. Therefore, our initial observation of differential ORN sensitivity in CTL vs LAK was a function of the progenitor cells; furthermore, CD8+ cytolytic cells are ORN sensitive whether activated by antigen (CTL) or IL-2 (T-LAK). PMID- 1899053 TI - Metabolism of phenylhydroquinone by prostaglandin (H) synthase: possible implications in o-phenylphenol carcinogenesis. AB - o-Phenylphenol (OPP) and its sodium salt sodium ortho-phenylphenate (NaOPP) are broad spectrum fungicides and antibacterial agents. Both are urinary bladder and renal carcinogens in the Fischer 344 rat. OPP is converted by mixed-function oxidases in the liver to phenylhydroquinone (PHQ). Since appreciable amounts of prostaglandin (H) synthase (PGS) are found in rat bladder and kidney-medullary papilla, the target sites of OPP- and NaOPP-induced tumors, we hypothesized that a secondary PGS-mediated activation of PHQ to phenylbenzoquinone (PBQ) may occur in the bladder and kidney. We have studied the metabolism of PHQ by PGS in the presence of arachidonic acid and hydrogen peroxide as co-factors. These studies showed that PHQ is indeed metabolized to a product having identical spectral and electrochemical properties to PBQ. The disappearance of PHQ with time was stoichiometric to the formation of PBQ. Less than 10% of PHQ was converted to PBQ in the absence of enzyme, indicating that auto-oxidation may play only a minor role in the conversion of PHQ to PBQ. Similar results were obtained when PGS was replaced with either myeloperoxidase or horseradish peroxidase and hydrogen peroxide as co-factor. These studies suggest that the peroxidative metabolism of PHQ by PGS to the reactive PBQ could play an important role in OPP-induced urinary bladder and kidney carcinogenesis in rats. PMID- 1899054 TI - Lack of correlation between hypersensitivity to cell killing and impaired inhibition of DNA synthesis in ataxia telangiectasia fibroblasts treated with 4 nitroquinoline 1-oxide. AB - Compared to normal controls from healthy subjects, cells cultured from patients with the autosomal recessive, cancer-prone disorder ataxia telangiectasia (AT) uniformly display impaired clonogenic survival, in concert with decreased inhibition of DNA synthesis, on exposure to ionizing radiation. In this study we have determined the effects of 4-nitroquinoline 1-oxide (4NQO), a partially radiomimetic chemical carcinogen, on colony-forming ability and rate of DNA synthesis in non-transformed skin fibroblasts strains derived from clinically normal volunteers and AT patients. Strain AT3BI, belonging to AT complementation group A, displayed substantial hypersensitivity to the lethal action of 4NQO, whereas the survival response of strain AT5BI (group D) did not differ significantly from that of the three normal controls. The 4NQO-hypersensitive AT3BI cells exhibited normal inhibition of DNA synthesis when treated with the chemical, as manifested by both dose-response and time-course measurements. However, 4NQO treatment decreased the rate of DNA synthesis to a much lesser degree in AT5BI than in normal strains. Hence, our data demonstrate unequivocally that, unlike that universally observed following exposure of AT cells to ionizing radiation, carcinogen-resistant DNA synthesis does not segregate with elevated cytotoxicity when cultured fibroblasts representing at least some genetic forms of AT (i.e. groups A and D) are damaged by 4NQO. PMID- 1899055 TI - Novel coumarins as potential anticarcinogenic agents. AB - The potential anticarcinogenic properties of several novel coumarin derivatives whose structures are based on polycyclic aromatic hydrocarbons (PAHs) were examined in the multistage model of mouse skin tumorigenesis. The test compounds were evaluated for their affinity to bind competitively with rat cytosolic Ah receptor in rat hepatic cytosol, their effects on mouse epidermal aryl hydrocarbon hydroxylase (AHH) after topical application, and for their effects on the levels of hydrocarbon-DNA adducts formed in vivo. All compounds showed good correlations between cytosolic Ah-receptor binding and their ability to induce epidermal AHH activity. Among the derivatives evaluated the coumarin (8-methyl-9H 10-oxabenzo[a]pyren-9-one) exhibited the highest affinity for the Ah-receptor and was also the most potent inducer of epidermal AHH activity. This compound also effectively inhibited the covalent binding of 7,12-dimethylbenz[a]anthracene (DMBA) to epidermal DNA when given either 5 min or 24 h prior to application of [3H]DMBA. This novel coumarin derivative significantly inhibited skin tumor initiation by DMBA in SENCAR mice when given at a dose of 200 nmol, 5 min (69% inhibition) or 24 h (76% inhibition) prior to initiation. The results of these studies suggest that this class of compounds shows considerable promise for future development as potential inhibitors of PAH-mediated tumor initiation on mouse skin. Potential mechanism(s) for the anti-initiating action of these compounds are discussed. PMID- 1899056 TI - Kinds and location of mutations induced by (+/-)-7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene in the coding region of the hypoxanthine (guanine) phosphoribosyltransferase gene in diploid human fibroblasts. AB - To gain insight into the mechanisms by which mutations are induced in human cells by carcinogens, we have determined the kinds and location (spectrum) of mutations induced in the coding region of the hypoxanthine (guanine) phosphoribosyltransferase (HPRT) gene by (+/-)-7 beta, 8 alpha-dihydroxy-9 alpha, 10 alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE). Individual populations of diploid human fibroblasts were treated with BPDE, or were left untreated (control). After a suitable expression period, the progeny cells were selected for resistance to 6-thioguanine. Individual drug-resistant colonies were isolated, and the mRNA in the lysate of 100-400 cells from each colony was copied directly into cDNA using reverse transcriptase. The cDNA of the HPRT gene of 29 unequivocally independent mutants from BPDE-treated populations and 13 from the control populations was amplified 10(11)-fold, and the product was sequenced directly. Twenty-three of the 29 BPDE-induced mutants examined contained a single base pair substitution; four exhibited two base pair substitutions. Eight out of 13 control mutants exhibited base pair substitutions, and four others were missing a complete exon. Thirty of the 32 base pair substitutions in the BPDE induced mutants involved G.C base pairs, primarily G.C----T.A transversions. The majority (89%) of the base pair substitutions observed in the mutants from the control population involved an A.T base pair. Base substitutions were found throughout the coding region of the gene, but 41% of those seen in mutants from the BPDE-treated population and 44% of those from the untreated population were located in the first half of exon 3. PMID- 1899057 TI - Identification of an aflatoxin G1-serum albumin adduct and its relevance to the measurement of human exposure to aflatoxins. AB - A major aflatoxin G1 (AFG1)-albumin adduct has been identified and characterized in rats following exposure to AFG1. The product isolated from a Pronase digest of in vivo-modified albumin was identical by chromatographic retention time to the synthetic product obtained by the acylase-catalysed deacetylation product of N alpha-acetyl-L-lysine with 8,9-dihydro-8,9-dibromo-AFG1. The in vitro product, AFG1-lysine, was characterized by UV, fluorescence, 1H- and 13C-NMR spectroscopy and fast atom bombardment MS. A competitive enzyme-linked immunoassay for this adduct was established using polyclonal antibodies to AFB1 and this was used together with an HPLC-fluorescence technique to quantitate the in vivo formation of AFG1-albumin adducts in comparison to AFB1. A linear dose-response relationship was observed in rats following single exposures to 0.1-3 mg AFG1/kg body wt. The levels of AFG1-albumin adducts were determined to be 5.7- and 2.8 fold lower than with equivalent doses of AFB1 as determined by immunoassay and HPLC fluorescence respectively. The lower binding of AFG1 and the lower levels in the human food supply compared to AFB1 suggest that the newly identified adduct could be added as an internal standard for methods using the measurement of aflatoxin-albumin adducts to quantitate human exposure to aflatoxin. PMID- 1899058 TI - Cathepsin D concentration in breast cancer cytosols: correlation with biochemical, histological, and clinical findings. AB - Cathepsin D (CD, EC 3.4.23.5) is a lysosomal protease induced by estrogen in certain estrogen receptor (ER)-positive breast cancer cell lines but produced constitutively by ER-negative cell lines. Our aims in this investigation were to study the distribution of CD in human breast cancers and to relate its concentrations to various biochemical, histological, and clinical characteristics. The concentrations of CD were significantly higher in breast carcinomas than in either normal breast tissues or benign breast tumors. In primary carcinomas, CD concentrations did not correlate with the concentrations of ER or with the estrogen-inducible protease t-PA. However, CD concentrations did correlate weakly but significantly with both UK-PA antigen and UK-PA activity. Also, CD concentrations did not correlate with either tumor stage or axillary node status but did correlate significantly with tumor grade. Patients with cancers containing high concentrations of CD had a significantly shorter overall survival than did patients with low concentrations of the enzyme. PMID- 1899059 TI - Elastase inhibitory activity in serum of patients with thyroid dysfunction. AB - Dermal elastic fiber fragmentation and decreased fiber density are characteristic cutaneous abnormalities in myxedema. We therefore evaluated elastase inhibitory activity in serum in thyroid dysfunctional states by measuring the protease inhibitor alpha 1-antitrypsin (A-1-AT), as well as by directly determining the inhibition of porcine pancreatic elastase activity. Overall there was a strong correlation between A-1-AT concentration and elastase inhibitory activity in serum (r = 0.95, P less than 0.001). Mean (+/- SE) A-1-AT concentrations were greatest in hyperthyroidism (39 +/- 3 mumol/L, n = 13), followed by normal controls (29 +/- 1, n = 11), subclinical hypothyroidism (27 +/- 2, n = 7), and hypothyroidism (25 +/- 1, n = 12). Concentrations of both A-1-AT and porcine pancreatic elastase inhibitory activity were significantly greater in subjects with hyperthyroidism than in the other groups (P less than 0.01). The correlations (r) between the overall free thyroxin (T4) index and A-1-AT and elastase inhibitory activity were 0.68 and 0.61, respectively (P less than 0.01), implying that free T4 variations account for 46% of the variance in A-1-AT concentrations and 37% of the variance in elastase inhibitory activity. We conclude that serum elastase inhibitory activity is increased in hyperthyroid patients. PMID- 1899060 TI - HPLC analysis of flecainide enantiomers in plasma: comparison with fluorescence polarization immunoassay. PMID- 1899061 TI - Further studies on thyroxin-binding globulin-dependence in equilibrium dialysis assays of free thyroxin. PMID- 1899062 TI - Carbonic anhydrase III in serum in muscular dystrophy and other neurological disorders: relationship with creatine kinase. AB - We measured with a radioimmunoassay the concentrations of carbonic anhydrase III (CA-III, EC 4.2.1.1) in sera from 68 patients with muscular dystrophy, 10 carriers of Duchenne muscular dystrophy (DMD), and 63 patients with other neurological disorders. The values obtained were compared with those for creatine kinase (CK, EC 2.7.3.2). Serum CA-III was strikingly increased in patients with DMD (mean, 274.4 micrograms/L) and congenital (Fukuyama-type) (182.8 micrograms/L) and limb-girdle (203.7 micrograms/L) dystrophies and positively correlated with the activities of CK in patients with DMD. CA-III concentration decreased with the subjects' age and the severity of the disease, similar to the tendency observed between age or severity and the concentration of CK. We found moderately increased CA-III in patients with polymyositis, myotonic dystrophy, amyotrophic lateral sclerosis, spinal progressive muscular atrophy, or Kugelberg Welander disease and in carriers of DMD. PMID- 1899063 TI - Radioimmunoassay of inhibin based on synthetic human inhibin alpha-chain peptide. AB - Polyclonal rabbit antisera were produced against cyclic human inhibin [(Cys6, Tyr7) alpha-(6-30)NH2] peptide, covalently conjugated to bovine serum albumin. The tyrosine residue introduced at position 7 facilitated the oxidative incorporation of radiolabel (125I) to yield a tracer with specific activity of 73.9 Ci/g. These reagents were used to develop a homologous equilibrium radioimmunoassay for human inhibin, with polyethylene glycol, 200 g/L, serving as the separation phase. At a detection limit of 2 micrograms/L (n = 7), immunoactive inhibin was detectable in human pre-ovulatory follicular fluid (128 micrograms/L), seminal plasma (2374 micrograms/L), amniotic fluid (66 micrograms/L), and placental extract (347 micrograms/L). We also demonstrated inhibin immunoreactivity in biological fluids from other mammalian species: macaque, chimpanzee, porcine, and bovine, but not rodent (guinea pig). Although the antisera were raised against a nonbioactive inhibin peptide, immunoglobulins fractionated on Protein A-Sepharose neutralized the bioactivity of human ovarian inhibin. Further characterization of inhibin immuno- and bioactivity was undertaken with immobilized heparin, divalent metal cations, and dye ligands. Only heparin-Sepharose distinguished between immuno- and bioactive inhibin. PMID- 1899064 TI - Diagnostic and genetic studies in 43 patients with classic cystinuria. AB - We present results for laboratory screening and diagnostic tests--cyanide nitroprusside test, semi-quantitative thin-layer chromatography, and quantitative amino acid column chromatography--of 43 patients with classic cystinuria. We report the efficaciousness of the cyanide-nitroprusside test and of thin-layer chromatography, as compared with quantitative amino acid chromatography, for detecting heterozygotes for type II or III cystinuria. The quantitative results for aminoaciduria in 57 blood relatives in 23 families were used to categorize the index patients with classic cystinuria. By column chromatography the ranges of excretion rates (mumol/24 h per 1.73 m2 body surface area) of diagnostic amino acids in the index patients were as follows: cystine 556-54044 (normal 20-128), arginine 131-11543 (10-80), lysine 768-21848 (51-514), ornithine 185-5685 (0-80). Also by column chromatography the median values for arginine and ornithine excretion in cystine-lysinuric heterozygotes (among the 57 blood relatives) were significantly higher (P less than 0.01) than in controls but never approached the values for homozygotes. The cyanide-nitroprusside test results were positive in urine samples of 41 of 43 index patients and in 16 (51.6%) of the urine samples of 31 obligate heterozygotes with column chromatographically proven cystine lysinuria. Thin-layer chromatography detected all of the homozygotes, all the compound heterozygotes, and 54.8% of the carriers. According to the type of aminoaciduria in their relatives, 11 patients with classic cystinuria could be classified as having classic cystinuria type I, 11 as having type II or III, and three as being compound heterozygotes. We discuss the implications of these results for correct diagnoses and for genetic studies in classic cystinuria. PMID- 1899065 TI - Spatial correlation between thyroid epithelial cells expressing class II MHC molecules and interferon-gamma-containing lymphocytes in human thyroid autoimmune disease. AB - In this immunohistochemical study we addressed the question whether aberrant class II MHC expression by thyroid epithelial cells (thyrocytes) in established thyroid autoimmune disease is the result of release of interferon-gamma (IFN gamma) by adjacent lymphocytes. Thyroids from eight cases of Hashimoto's thyroiditis, 13 cases of Graves' disease and 10 cases of focal thyroiditis were studied. Both thyrocytes expressing class II MHC and lymphocytes containing immunoreactive IFN-gamma were found in all 31 autoimmune thyroids. In a serial section study of these thyroids, IFN-gamma-expressing lymphocytes were found within 50 microns of class II MHC-positive thyrocytes in 89% of 282 randomly selected fields. Conversely, class II MHC-positive thyrocytes were found within 50 micron of aggregates of IFN-gamma-positive lymphocytes in 82% of 272 randomly selected fields. These findings support the view that in established thyroid autoimmune disease expression of class II MHC by thyrocytes is the result of local release of IFN-gamma. PMID- 1899067 TI - The case of Nancy Cruzan: the Supreme Court's decision. PMID- 1899068 TI - PEG ileus. A new cause of small bowel obstruction. AB - A case of small bowel obstruction due to a lodged percutaneous endoscopic gastrostomy tube inner bumper is described. Most probably inner bumper lodgement in the terminal ileum is related to its size. Laparotomy was required to remove the bumper and relieve the obstruction. We suggest that all percutaneous endoscopic gastrostomy bumpers be retrieved endoscopically when the PEG tube is removed or replaced unless a collapsible inner bumper is used. PMID- 1899066 TI - Triggered human mucosal T cells release tumour necrosis factor-alpha and interferon-gamma which kill human colonic epithelial cells. AB - T cell activation can lead to local tissue injury in organ culture studies of human fetal jejunum, either directly through cytotoxicity or indirectly by the release of cytotoxic cytokines. The goal of this study was to establish in vitro whether cytotoxic cytokines can be released by isolated colonic T cells and what cytokine interactions are required for killing of human colonic epithelial cells. Cytokine-containing supernatants were induced by incubating unseparated lamina propria lymphocytes (LPL) or mucosal T cell subpopulations (separated by indirect panning) with anti-CD3 and/or K562 target cells for 18 h at 37 degrees C. Cytokines were measured by cytotoxicity assays using L929 (murine fibroblast) and HT-29 (human colonic tumour) lines as target cells in combination with blocking anti-cytokine antibodies. Supernatants derived from unseparated, CD4+ (greater than 95% pure) and CD8+ (greater than 90% pure) LPL were cytotoxic to L929 targets (350 U/ml, 230 U/ml and 100 U/ml tumour necrosis factor-alpha, respectively). All or nearly all of the cytotoxicity was due to the presence of tumour necrosis factor-alpha (little or no tumour necrosis factor-beta was detected). These same supernatants were cytotoxic (up to 32% lysis at 1/4 dilution) to HT-29 targets in a 48-h 111In release assay. Recombinant tumour necrosis factor-alpha and interferon-gamma alone produced minimal killing of HT 29, but together killed the HT-29 target cells. Anti-tumour necrosis factor-alpha or anti-interferon-gamma alone blocked killing of HT-29 target cells by LPL derived supernatants, although anti-tumour necrosis factor-beta had no effect upon killing of HT-29. These results demonstrate that human LPL T cells, triggered by addition of anti-CD3 and target cells, produce tumour necrosis factor-alpha and interferon-gamma, both of which are required for optimal killing of HT-29. Simultaneous release of these cytokines in the vicinity of epithelial cells during immune responses could play an important role in the mucosal damage in chronic inflammatory states such as inflammatory bowel disease. PMID- 1899069 TI - Chromosomal behavior in starfish (Asterina pectinifera) zygotes under the effect of aphidicolin, an inhibitor of DNA polymerase. AB - When calf thymus histones were labeled fluorescently and microinjected into oocytes of the starfish, Asterina pectinifera, the labeled histones visualized chromosomes during maturation division and cleavage. In doing so, we confirmed the previously reported phenomenon that chromosomes became incompetent at the first cleavage in the aphidicolin-treated egg, although cleavage itself took place. Moreover, we found that chromosomes were aligned at the equator of the metaphase spindle of the first cleavage and that they did not separate into two groups at all, but made a lump in the middle of the spindle. Chromosomes finally entered one blastomere, although they did not participate in the following karyokinesis. DNA and microtubules were examined by cytochemistry and immunofluorescence in order to investigate the relation between chromosome movement and the microtubular cytoskeleton. The mitotic apparatus developed and grew in the aphidicolin-treated cells in the same manner as those in normal cells without normal chromatin condensation or chromosome movement during the first cleavage. However, the mitotic apparatus consisted of two asters without the spindle formed at subsequent cleavages. Electron microscopic study revealed that chromosomes did not condense normally and kinetochores were not detected during the first cleavage. These results indicate that the dynamic changes in microtubular structures during mitosis have poor relation with the chromosome behavior such as prophase chromosome condensation and anaphase chromosome movement. PMID- 1899070 TI - Disruption of the Golgi apparatus by brefeldin A inhibits the cytotoxicity of ricin, modeccin, and Pseudomonas toxin. AB - We have studied the cytotoxicity of ricin in cells treated with brefeldin A (BFA), which dramatically disrupts the structure of the Golgi apparatus causing Golgi content and membrane to redistribute to the ER. BFA inhibits the cytotoxicity of ricin in Chinese hamster ovary, normal rat kidney, and Vero cells and abolishes the enhancement of ricin cytotoxicity by NH4Cl, nigericin, swainsonine, and tunicamycin or by a mutation in endosomal acidification. BFA protects cells from the cytotoxicities of modeccin and Pseudomonas toxin, but has no effect on the intoxication by diphtheria toxin. Pretreatment of BFA does not protect cells from ricin treatment in the absence of BFA. Our results suggest that ricin, modeccin, and Pseudomonas toxin share a common pathway of intracellular transport from endosomes to the Golgi region where they are released into the cytosol. In contrast, the lack of protection of Vero cells from diphtheria toxin by BFA indicates that diphtheria toxin is released from acidified endosomes without involving the Golgi region. PMID- 1899071 TI - Association of glycosphingolipids with intermediate filaments of human umbilical vein endothelial cells. AB - Our previous studies of glycosphingolipids (GSLs) of human umbilical vein endothelial cells (HUVECs) established that globoside and ganglioside GM3 are the most abundant GSLs of HUVECs. Both compounds are located intracellularly, as well as on the cell surface. In this study, we demonstrate that the intracellular globoside and GM3 antigens are associated with the vimentin intermediate filaments of the HUVEC cytoskeleton. Immunofluorescence staining of fixed, permeabilized HUVECs showed colocalization of globoside and GM3 with vimentin but not with tubulin or actin. Both GSLs remained associated with intermediate filaments after perinuclear collapse of the filaments induced by colcemid. Indirect evidence that the globoside epitope is present on a GSL is the loss of staining by anti-globoside after methanol fixation and the absence of anti globoside reactivity with HUVEC proteins on immunoblots. Colocalization of anti globoside and anti-vimentin was also demonstrated in cryosections of endothelial cells, which indicates that the observed association was not an artifact induced by exposure of cells to detergent or organic solvent. Association of globoside with intermediate filaments was confirmed by immunoelectron microscopy, which demonstrated the presence of antigen along intermediate filaments, as well as on the cell surface and on lipid vesicles. Interferon-gamma decreased the ratio of surface to filamentous globoside staining, but had the opposite effect on GM3 distribution. Less abundant HUVEC GSLs, including Gb3, nLc4, IV2FucnLc4, and IV3NeuAcnLc4, were not detected along filaments. This is the first report of the association of GSLs with intermediate filaments. We suggest that intermediate filaments may play a role in the transport of GSLs. PMID- 1899072 TI - Urokinase-type and tissue-type plasminogen activators are essential for in vitro invasion of human melanoma cells. AB - This study evaluates the contribution of two types of plasminogen activators (PAs; tissue-type PA (tPA) versus urokinase-type PA (uPA) toward the invasiveness of human melanoma cells in a novel in vitro assay. We identified two human melanoma cell lines, MelJuso and MeWo, expressing uPA or tPA as shown at mRNA, protein, and enzyme activity level. MelJuso cells produced uPA as well as plasminogen activator inhibitor-1 (PAI-1). The latter was, however, not sufficient to neutralize the cell-associated or secreted uPA activity. MeWo cells secreted tPA, but the enzyme was not found to be cell-associated. PAI-1 production by these cells was not detectable. Plasminogen activation and fibrinolytic capacity of both cell lines were reduced by anticatalytic monoclonal antibodies specific for the respective type of PA or by aprotinin. In a novel in vitro invasion assay, antibodies to PA as well as aprotinin decreased the invasiveness of both cell lines into a fibrin gel, Matrigel, or intact extracellular matrix. Our results confirm the importance of uPA-catalyzed plasminogen activation in tumor cell invasiveness. Furthermore, we provide evidence that tPA, beyond its key role in thrombolysis, can also be involved in in vitro invasion of human melanoma cells. PMID- 1899073 TI - Influence of the cytocidal macrophage phenotype on the degradation of acetylated low density lipoproteins: dual regulation of scavenger receptor activity and of intracellular degradation of endocytosed ligand. AB - The appearance of lipid-laden macrophages is a characteristic feature in the development of the atherosclerotic plaque. The functional status of macrophages located within the intima of atherosclerotic lesions is as yet unknown; nevertheless, macrophages are known to be exceedingly responsive to their environment and can differentiate to different functional states. The objective of this study was to determine the influence of two definable macrophage functional states, namely the IFN-primed state and the cytocidal state, on the capacity of macrophages to bind and degrade lipoproteins. We report that priming of macrophages with IFN-beta or IFN-gamma failed to influence the ability of macrophages to degrade native low density lipoprotein or acetylated low density lipoprotein (AcLDL). However, challenge with stimuli that induce expression of the cytocidal state (poly[I:C] and LPS) resulted in a marked inhibition of the capacity of the cells to degrade both lipoproteins. The poly[I:C]-induced inhibition of 125I-AcLDL degradation was accompanied by a proportional decrease in the binding of the ligand to its receptor which Scatchard analysis revealed was due to a decrease in receptor number rather than a change in receptor affinity for 125I-AcLDL. However, in addition to the down-regulation of receptor activity, the degradation of endocytosed 125I-AcLDL was also suppressed in macrophages that had been exposed to poly[I:C]. This latter observation suggests that the degradation of endocytosed lipid is also regulated at a second, previously unidentified level, independent of the availability of cell surface ligand receptors. We speculate that this down-regulation in the intracellular hydrolysis of endocytosed lipid may account for the observed accumulation of 125I AcLDL in these cells. PMID- 1899074 TI - Tumor necrosis factor and epidermal growth factor modulate migration of human microvascular endothelial cells and production of tissue-type plasminogen activator and its inhibitor. AB - Epidermal growth factor (EGF) induces tubular formation of cultured human microvascular endothelial (HME) cells in the gel matrix containing collagen, and tumor necrosis factor (TNF) disrupts the tubular formation (Mawatari et al. (1989) J. Immunol. 143, 1619-1627). Here we studied the effects of EGF and TNF on endothelial cell migration and on the production of proteases. Confluent HME cells, when wounded with a razor blade, moved into the denuded space. This migration was stimulated by EGF and inhibited by TNF in this assay and in the Boyden chamber assay. Antibody against tissue-type plasminogen activator (t-PA) inhibited the EGF-stimulated cell migration in both assays by approximately 70%, but antibody against urokinase-type plasminogen activator (u-PA) could not inhibit its migration. Quantitative immunoreactive assays showed an approximately three- to fourfold increase of t-PA at 6 to 12 h after EGF addition, and TNF inhibited the production of t-PA by 50%. Northern blot analysis showed increased expression of t-PA mRNA by EGF alone in a time- and dose-dependent manner, whereas TNF alone inhibited its expression in a time- and dose-dependent manner. Northern blot analysis showed a significant increase of plasminogen activator inhibitor-1 (PAI-1) mRNA when EGF or TNF was present. Stimulation by EGF of cell migration of HME cells and its inhibition by TNF appear to be closely correlated with the cellular modulation of t-PA and PAI-1 activities. PMID- 1899075 TI - N-linked oligosaccharide processing and autocrine stimulation of tumor cell proliferation. AB - Somatic mutations which impair complex-type N-linked oligosaccharide processing and chemical inhibitors of processing have been shown to reduce metastatic potential in several experimental tumor models. In this report, we demonstrate that glycosylation mutants of the metastatic MDAY-D2 tumor cell line with either truncated glycans lacking sialic acid and galactose or a mutant with less branched N-linked oligosaccharides grow more slowly in serum-free medium (SFM) than do MDAY-D2 cells. In medium containing fetal calf serum, growth rates of the cell lines were similar. A revertant of the former mutation showed a return to a more rapid growth rate in SFM. The N-linked processing inhibitor swainsonine also reduced cell growth rate in SFM but not in serum-containing medium. One of five randomly selected clones of the MDAY-D2 tumor cell line showed a slower growth rate in SFM and also showed decreased expression of branched N-linked oligosaccharides. These observations suggest that in MDAY-D2 cells, optimal factor-independent stimulation is dependent upon expression of branched complex type N-linked oligosaccharides. The growth rate of MDAY-D2 cells in SFM was dependent on the initial seeding density of the cultures, and medium conditioned by the cells accelerated the growth of low-density cultures, suggesting that the cells respond to an autocrine factor. Culture supernatants conditioned by mutant and wild-type cells had similar levels of growth-stimulating activity. However, both mutants and swainsonine-treated cells were less responsive to this growth stimulating activity. The growth rates of the MDAY-D2 tumor cell lines in vivo as subcutaneous tumors correlated with their relative growth rates in SFM in vitro. The results suggest that branched complex-type N-linked oligosaccharides commonly expressed in malignant cells are required for optimal autocrine-dependent growth in vitro and may be a significant factor in tumor progression in vivo. PMID- 1899076 TI - Localization of paxillin, a focal adhesion protein, to smooth muscle dense plaques, and the myotendinous and neuromuscular junctions of skeletal muscle. AB - In this report we have demonstrated that paxillin, a cytoskeletal protein which is present in focal adhesions, localizes in vivo to regions of cell-extracellular matrix interaction which are believed to be analogous to focal adhesions. Specifically, it is enriched in the dense plaques of chicken gizzard smooth muscle tissue and in the myotendinous junctions formed in Xenopus laevis tadpole tail skeletal muscle. In addition, paxillin was identified at the rat diaphragm neuromuscular junction. The distribution of paxillin is thus comparable to that of other focal adhesion proteins, for example, talin and vinculin, in these structures. PMID- 1899077 TI - Regulation of autologous T-lymphocyte clones on in vitro growth of BFU-e: enhancing effects of both CD4- and CD8-positive clones. AB - In order to characterize the effect of T lymphocytes on the in vitro growth of erythroid progenitor cells (EPC), we have optimized an assay for evaluating the influence of autologous T-lymphocyte clones on BFU-e, grown from PBMNCs depleted of T lymphocytes. Testing a large number of T-lymphocyte clones from 2 individuals we found that, irrespective of immunological phenotype, all clones tested were found to enhance the growth of BFU-e. Thus, no evidence for a functional dichotomy between CD4+ and CD8+ T lymphocytes was found in this system. The enhancing effect worked across a histocompatibility barrier and was, at least in part, mediated by soluble factors. We therefore conclude that the role of the majority of cloned normal T lymphocytes in the regulation of the in vitro growth of EPC is a supportive one. PMID- 1899078 TI - Our aging parents. Heartbreaking decisions: a personal perspective. PMID- 1899079 TI - Intranasal buserelin versus surgery in the treatment of uterine leiomyomata: long term follow-up. AB - Forty-two women with symptomatic uterine myomas, candidates for myomectomy or hysterectomy, were randomized to 6 months' treatment with buserelin 1200 micrograms/day intranasally (n = 22) or immediate surgery (n = 20). After buserelin treatment or operation the patients were followed for at least 12 months. Buserelin was well tolerated, the uterine volume fell from 465 +/- 168 to 273 +/- 88 cm3, and hemoglobin values normalized in all anemic patients. Rapid myoma regrowth was observed in all patients in the buserelin group after treatment withdrawal. Pregnancy occurred during follow-up in one of five buserelin-treated myomectomy candidates. Menorrhagia recurred in eight of 15 buserelin-treated hysterectomy candidates, and a hysterectomy was required but no transfusion was needed. Two women entered natural menopause and were considered cured. In the surgery group all operations were uneventful: three women conceived after myomectomy, whereas four of the patients that underwent hysterectomy required transfusions. Thus buserelin treatment appears to be indicated for infertile patients when surgery is contra-indicated or could cause adhesions, and for hysterectomy candidates in perimenopausal age and/or with secondary anemia. PMID- 1899080 TI - Hemodynamic study during transdermal application of nitroglycerin tape in patients with cirrhosis. AB - We studied 14 patients with portal hypertension and cirrhosis using portal and hepatic vein catheterizations to determine the effects of transdermal application of nitroglycerin tape (containing 10 mg of nitroglycerin and capable of releasing 6 to 7 mg of nitroglycerin in 12 hr) on splanchnic hemodynamics. Patients randomly received nitroglycerin (n = 7) or a placebo (n = 7). No significant changes were observed after the administration of the placebo. In contrast, transdermal nitroglycerin caused a significant reduction in portal pressure, as evaluated by measurements of the portal venous pressure gradient (-22%, p less than 0.01). The reduction of portal pressure was due to a decrease in the portal venous pressure, with no changes in the free hepatic venous pressure. Despite the fall in portal pressure, the hepatic blood flow was maintained. These findings suggest that transdermal nitroglycerin could be potentially useful in the treatment of portal hypertension associated with cirrhosis. PMID- 1899081 TI - Detection of hepatitis B virus DNA in paraffin-embedded liver tissues in chronic hepatitis B or non-A, non-B, hepatitis using the polymerase chain reaction. AB - We developed a polymerase chain reaction assay for the direct detection of hepatitis B virus in paraffin-embedded liver tissue and applied this assay to determine whether hepatitis B virus DNA exists in livers with chronic hepatitis non-A, non-B. Fifty five liver biopsy samples were studied: 11 from patients with HBeAg-positive chronic hepatitis (paraffin-embedded) and 44 from patients with chronic hepatitis non-A, non-B (21 paraffin-embedded; 25 fresh frozen). Thirty three (75%) of the non-A, non-B cases were positive for hepatitis C virus antibodies. Approximately 1 to 10 ng of DNA was extracted from the paraffin embedded tissue and amplified using oligonucleotide (23-mer) primers specific for the S gene (positions 261 to 692). The beta-globin gene was used as an internal control for sensitivity because this is a single copy gene and allows for relative quantification. In each of the chronic hepatitis B livers, the expected 432-base-pair amplification product for hepatitis B virus DNA and beta-globin gene product were both detected. On the other hand, in the 21 paraffin-embedded chronic hepatitis non-A, non-B livers, no hepatitis B virus DNA was detected, although beta-globin gene was observed in all. Furthermore, in all 25 frozen non A, non-B livers, beta-globin gene was observed, but no hepatitis B virus band was seen. The limit of detection of hepatitis B virus DNA by this method was estimated to be one genomic copy of hepatitis B virus DNA per cell.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1899083 TI - Medicaid expansion creates new dilemmas for state programs. AB - At the same time advocates for the poor are rejoicing over Medicaid program expansions passed as part of the FY 1991 federal budget, state Medicaid directors are wondering how to accommodate all the potential new recipients. Ironically, because of budget pressures at the state level, the new federal mandates could force some current program recipients off the rolls in order to allow new ones on. "Expanding obstetrical and prenatal care is something we want to do because it's sound social policy--but the mandates have been compressed into time frames that are too short for state budgets," says one state Medicaid director. PMID- 1899082 TI - Expression of specific UDP-glucuronosyltransferase isoforms in carcinogen-induced preneoplastic rat liver nodules. AB - The expression of specific UDP-glucuronosyltransferase isoforms in 2 acetylaminofluorane-induced rat liver preneoplastic nodules was studied; livers from pair-fed littermates were used as controls. For comparison, liver and kidney from 3-methylcholanthrene-treated or untreated (control) rats were used. Steady state UDP-glucuronosyltransferase mRNA levels were determined by Northern blot analysis or in situ hybridization of tissue sections using a 30-mer oligonucleotide specific for the 3-methylcholanthrene-inducible UDP glucuronosyltransferase (which is active toward 4-nitrophenol) or a double stranded cDNA probe specific for androsterone-UDP-glucuronosyltransferase. For 3 methylcholanthrene-inducible UDP-glucuronosyltransferase, the mRNA level was very low in control liver; there was a 15-fold increase after 3-methylcholanthrene treatment. This mRNA was present at relatively high concentration in the kidney and there was a threefold increase after 3-methylcholanthrene administration. In livers with preneoplastic nodules 1 mo after cessation of carcinogen administration, this mRNA concentration was approximately 15 times greater than in control liver. Similar changes in the level of the 3-methylcholanthrene inducible UDP-glucuronosyltransferase were also observed by in situ hybridization of tissue sections. Immunocytochemical studies using an antiserum that recognizes the 3-methylcholanthrene-inducible UDP-glucuronosyltransferase showed a marked increase in the concentration of this isoform in preneoplastic nodules compared with the adjacent nonnodular liver. PMID- 1899084 TI - Alpha 2,6 sialylation of N-acetyllactosaminic sequences in human colorectal cancer cell lines. Relationship with non-adherent growth. AB - In a previous work we found that human colorectal cancer tissues express increased levels of an alpha 2,6 sialyltransferase (alpha 2,6 ST) acting on N acetyllactosaminic sequences (E.C. 2.4.99.1). In this study we have taken advantage of the known specificity of elderberry bark lectin (Sambucus nigra agglutinin, SNA) for NeuAc alpha 2, 6Gal/GalNAc structures to investigate the relationship between expression of alpha 2,6 sialyltransferase activity and occurrence of alpha 2,6-sialylated oligosaccharide sequences in human colorectal cancer cell lines. Three cell lines with opposite adhesion properties were used in this study: SW 948 cells grow adherent to the culture flask surface and express very low levels of enzyme activity; COLO 205 cells grow in non-adherent form and express the highest levels of alpha 2,6 ST activity; A non-adherent subline of SW 948 cells (SW 948 FL) was isolated and found to express high levels of alpha 2,6 ST activity. By using SNA-Sepharose chromatography we found that expression of alpha 2,6 ST activity correlates with the extent of alpha 2,6 sialylation of N-linked chains of glycoproteins but not with the presence of alpha 2,6-sialylated glycolipids. PMID- 1899085 TI - Incidence of pulmonary aspiration in intubated patients receiving enteral nutrition through wide- and narrow-bore nasogastric feeding tubes. AB - A descriptive study was performed to compare the incidence of pulmonary aspiration in 25 critically ill patients who had endotracheal tubes in place and were receiving enteral nutrition through a narrow-bore nasogastric tube (n = 10) or a wide-bore nasogastric tube (n = 15). Results of chi-square analysis of this comparison were not significant, p less than 0.05. Aspiration occurred in one subject. The amount and rate of tube feeding delivered was examined. The number of checks for residual feeding was found to be significantly greater in the wide bore tube group. A comparison of the assessment of nasogastric tube placement on x-ray examination showed that tube placement was reported on x-ray results with more frequency in the wide-bore group. Questions are raised by these observations regarding the use of narrow-bore tubes in the critically ill population with endotracheal tubes in place. PMID- 1899087 TI - Polyarthritis: an unusual side effect of lithium. PMID- 1899086 TI - Menstrual irregularities associated with bupropion treatment. AB - The authors report two cases of menstrual irregularities associated with bupropion treatment. This is the first report of such an association, and it is supported by data collected by the Burroughs Wellcome Co. Since the mode of action of this effective new antidepressant is basically unknown and does not operate through any of the putative mechanisms of the classical antidepressants, its side effect profile is of heuristic as well as practical importance. PMID- 1899088 TI - Synchronized oscillation of Ca2+ entry and Ca2+ release in agonist-stimulated AR42J cells. AB - Oscillation in [Ca2+]i induced by agonists has been described in many cell types and is thought to reflect Ca2+ release from and uptake into internal stores. We measured [Ca2+]i and Mn2+ entry in single cells of the pancreatic acinar cell line AR42J loaded with Fura 2 to examine the behavior of Ca2+ influx across the plasma membrane (Ca2+ entry) during agonist-evoked [Ca2+]i oscillation. Addition of extracellular Ca2+ (Ca2+out) to agonist-stimulated cells bathed in Ca2(+)-free medium resulted in a marked [Ca2+]i increase blocked by La3+. The use of Mn2+ as a congener of Ca2+ to follow unidirectional Ca2+ movement reveals an oscillatory activation of Ca2+ entry by Ca2(+)-mobilizing agonists. The frequency at which Ca2+ entry oscillated matched the frequency of Ca2+ release from intracellular stores. Ca2+ entry is activated after completion of Ca2+ release and is inactivated within the time span of each [Ca2+]i spike. These studies reveal a new aspect of [Ca2+]i oscillation in agonist-stimulated cells, that is the oscillatory activation of [Ca2+]i entry during [Ca2+]i oscillation. PMID- 1899089 TI - Biochemical and molecular characterization of three barley seed proteins with antifungal properties. AB - We have purified three proteins from barley (Hordeum vulgare L.) seeds which synergistically inhibit the growth of fungi measured in a microtiter well assay. The proteins are a 26-kDa chitinase, a 30-kDa ribosome-inactivating protein, and a 32-kDa (1-3)-beta-glucanase. Full-length cDNAs encoding them were isolated and sequenced to determine the complete primary structures of the proteins. Northern hybridizations with the cDNAs as probes showed that the corresponding mRNAs accumulate differentially during seed development and germination. Chitinase mRNA accumulates to high levels in aleurone cells during late seed development and early germination, while high levels of mRNA encoding the ribosome-inactivating protein accumulate only in the starchy endosperm during late seed development. The glucanase mRNA accumulates to low levels during seed development and to higher levels in aleurone and seedling tissues during germination. Southern hybridizations showed that the three proteins are encoded by small families of three to eight genes. Their biological roles and potential use in genetic engineering studies are discussed. PMID- 1899090 TI - Construction and characterization of the chimeric enzymes between the Bacillus subtilis cellulase and an alkalophilic Bacillus cellulase. AB - The amino acid sequences of cellulase from Bacillus subtilis (BSC) and that from an alkalophilic Bacillus sp. N-4 (NK1) show significant homology in most parts except for the C-terminal portions. Despite the high homology, the pH activity profiles of the two enzymes are quite different; BSC has its optimum pH at 6-6.5, whereas NK1 is active over a broad pH range from 6 to 10.5. In order to identify the structural features which determine such pH activity profiles, chimeric cellulases between BSC and NK1 were constructed using four restriction sites commonly present within the homologous coding sequences, and were produced in Escherichia coli. The chimeric cellulases showed various chromatographic behaviors, reflecting the origins of their C-terminal regions. The pH activity profiles of the chimeric enzymes in the alkaline range could be classified into either the BSC or NK1 type mainly depending on the origins of the fifth C terminal regions. In the acidic range, the profile was determined only by the origin of the fourth enzyme region from the N terminus. Comparison of the kinetic parameters between pH 5 and 6 using p-nitrophenyl cellobioside as a substrate indicated that the fourth region is responsible for the pH-dependent change of the kcat value. Only a limited number of amino acids in the fourth region may affect on deprotonation of catalytic residues of the cellulases and modulate the catalytic activity in the acidic pH values. PMID- 1899091 TI - Energization of amino acid uptake by system A in cultured human fibroblasts. AB - The energization of System A in cultured human fibroblasts has been studied by measuring the energy transfer from the electrochemical gradient of Na+ to the chemical gradient of the site A-specific substrate amino acid 2 methylaminoisobutyric acid. The co-transport Na+/amino acid, studied by kinetic analysis and radiochemical measurements, showed a coupling ratio of 1:1. The assessment of the Na+ electrochemical gradient in cultured adherent cells relied on the development of noninvasive procedures as follows: the membrane electrical potential was estimated from the accumulation of L-arginine at equilibrium (Bussolati, O., Laris, P. C., Nucci, F. A., Dall'Asta, V., Longo, N., Guidotti, G. G., and Gazzola, G. C. (1987) Am. J. Physiol. 253, C391-C397); the chemical gradient of Na+ was determined from spectrometric measurements of Na+. The accumulation of 2-methylaminoisobutyric acid was strongly sensitive to changes of Na+ gradient and of membrane electrical potential, indicating that the electrochemical gradient of Na+ contributed energy for the uphill transport of the amino acid through System A. Changes in the Na+ electrochemical gradient were obtained by: (i) alterations of extracellular concentration of Na+; (ii) changes of membrane electrical potential obtained by variation of extracellular [K+]; and (iii) changes of [Na+]in and membrane electrical potential upon incubation of the cells in serum-free saline solutions (Dall'Asta, V., Gazzola, G. C., Longo, N., Bussolati, O., Franchi-Gazzola, R., and Guidotti, G. G. (1986) Biochim. Biophys. Acta 860, 1-8). The correlation between the chemical gradient of 2 methylaminoisobutyric acid and the Na+ electrochemical potential followed a straight line with a yield close to the thermodynamic equilibrium, thus suggesting that the energy stored in the gradient of Na+ electrochemical potential is fully adequate to energize the intracellular accumulation of site A reactive amino acids in human fibroblasts. PMID- 1899092 TI - Identification of distinct endoglycosidase (endo) activities in Flavobacterium meningosepticum: endo F1, endo F2, and endo F3. Endo F1 and endo H hydrolyze only high mannose and hybrid glycans. AB - Flavobacterium meningosepticum endo-beta-acetyl-glucosaminidase F preparations have been resolved by hydrophobic interaction chromatography on TSK-butyl resin into at least three activities designated endo F1, endo F2 and endo F3 each with a unique substrate specificity. The 32-kDa endo F1 protein is the principle component representing in excess of 95% of most earlier and currently available commercial endoglycosidase preparations, the remainder being a mixture of five proteins from 32 to 43 kDa. Substrate specificity studies reveal endo F1 and endo H from Streptomyces plicatus to have nearly identical capacities to hydrolyze high-mannose oligosaccharides with a minimum Man1 alpha 3Man1 alpha 6Man1 beta 4GlcNAc1 beta 4GlcNAc structure. Although endo H will hydrolyze fucose-containing hybrid oligosaccharides at rates approaching comparable high-mannose forms, core linked fucose reduces the hydrolysis rate of endo F1 by over 50-fold relative to high-mannose structures. Neither homogeneous endo F1 nor endo H hydrolyze complex multi-antennary glycans. The biantennary cleaving activity previously reported for endo F preparations (Tarentino, A. L., Gomez, C. M., and Plummer, T. H., Jr. (1985) Biochemistry 24, 4665-4671) is a characteristic of the contaminating endo F2 activity. PMID- 1899093 TI - Characterization of recombinant human Kirsten-ras (4B) p21 produced at high levels in Escherichia coli and insect baculovirus expression systems. AB - Kirsten-ras is the oncogene most frequently activated in human tumors. Studies of its biological function have been limited by the nonavailability of significant amounts of the major protein product, Kirsten-ras (4B) p21. When expressed in Escherichia coli K12, the recombinant protein was rapidly cleaved upon cell lysis in the lysine-rich C terminus region, probably by the ompT protease. However, soluble full-length protein was obtained when the Kirsten-ras gene was expressed in an E. coli strain lacking the ompT gene, and also in a baculovirus/insect cell expression system. Additionally, the baculovirus/insect cell system produced about half of the Kirsten-ras protein in a membrane-associated form, which was post-translationally modified by polyisoprenylation and carboxyl-methylation. A C terminally truncated form (residues 1-166) was also expressed at high levels in E. coli for x-ray crystallographic studies. The kinetics of GDP release and of GTP hydrolysis of the purified proteins are similar to those of the corresponding Harvey-ras proteins, though there are small differences in the relative affinities for GDP and GTP. Biological activity of full-length Kirsten Val-12 p21 was demonstrated by microinjection into Swiss 3T3 cells, resulting in morphological transformation, with a lower potency than that of Harvey Val-12 protein. PMID- 1899094 TI - Regulation of the G-protein alpha i-2 subunit gene in LLC-PK1 renal cells and isolation of porcine genomic clones encoding the gene promoter. AB - Heterotrimeric G-proteins function as signal transducers for a variety of hormone coupled enzyme and ion transport systems in eukaryotic cells. We have studied G protein-coupled processes that appear to be developmentally regulated in polarized pig kidney cells (LLC-PK1). Following trypsinization, LLC-PK1 cells differentiate from a rounded cell type to a fully polarized epithelium by 7 days of culture. During this differentiation, the expression of G-protein alpha i-2 subunit mRNA was not detected until day 4 of culture, it peaked at day 6, and declined thereafter. In contrast, G-protein alpha s subunit mRNA which peaked on day 4 was easily detected on all culture days. The presence of the alpha i-2 protein on epithelial cell basolateral membranes followed the same pattern of mRNA expression during culture. To understand the developmental expression of the alpha i-2 subunit in non-polarized cells and its potential regulation by hormones and second messengers in polarized cells at the transcriptional level, genomic DNA segments encoding the alpha i-2 gene promoter were isolated from an EMBL-3 porcine genomic library. S1 nuclease analysis of LLC-PK1 mRNA with cRNA probes derived from these DNA segments revealed major and a minor transcriptional start sites 131 and 171 base pairs upstream of the translation initiation site. The porcine and human alpha i-2 subunit genes shared a 78% sequence identity in their 5' flanks which suggested an evolutionary conservation of cis elements required to influence their transcription. The porcine alpha i-2 gene promoter was identified by fusing DNA segments encoding putative 5'-flanking areas of the gene to a plasmid that contained a firefly luciferase reporter gene but lacked a promoter. The minimal promoter was found between -130 and -60 base pairs from the major transcription start site. No typical "TATA-like" sequences were found. However, a "GC" box and a "TGTGG" sequence were two potential cis elements required for basal transcription of the porcine gene promoter which shared a 76% sequence identity to the promoter of another GTP-binding protein, the human c-Ha ras proto-oncogene. Transcription of the gene was inhibited following treatment of renal cells with 10(-8) M dexamethasone.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1899095 TI - Bilateral spontaneous arthrodesis of the hip after combined shelf acetabular augmentation and femoral varus osteotomies. AB - Spontaneous arthrodesis occurred after bilateral, extraarticular shelf augmentation and femoral varus osteotomies in a child with dislocated hips secondary to muscle imbalance from cerebral palsy. The proposed cause is heterotopic bone formation in the hip abductors in the face of insufficient range of motion exercise. PMID- 1899096 TI - Financial aspects of medical care. PMID- 1899097 TI - Thymic deletion of V beta 11+, V beta 5+ T cells in H-2E negative, HLA-DQ beta+ single transgenic mice. AB - DQw6b transgenic mice have been generated by microinjecting a linearized cosmid clone containing 34-kb DQb genomic DNA, isolated from HLA-homozygous B cell line AKIBA (DR2, Dw12, DQw6), into embryos of (CBA x B10.M)F2 or (SWR x SJL)F2. Among 85 mice screened, eight mice were transgene-positive. The transgene in seven of eight founders was germline-transmitted. FACS analysis and immunohistochemical studies with DQ beta-specific mAb demonstrated that DQ beta molecules in association with mouse A alpha f molecules are expressed on peripheral mononuclear cells, spleen cells, and in thymic medulla. More interestingly, V beta 11-, V beta 5.1-, and V beta 5.2-bearing T cells, but not V beta 8.2-bearing T cells, were clonally deleted in the H-2E-negative but DQ beta+ progeny of two selected founders (260-23 and 258-10). The deletion was found to take place intrathymically during the transition stage from immature to mature thymocyte development. We postulate that although human DQ genes are more homologous to mouse H-2A genes, A alpha f/DQ beta hybrid molecules may possess the same self peptide- (or superantigen)-presenting epitope as E alpha/E beta molecules critical for deletion of V beta 11-, V beta 5.1-, and V beta 5.2-bearing T cells in thymus. Our results also confirm the previous findings that accessory molecules on thymocytes such as CD4 may be involved in thymic selection, and further suggest that an interaction of mousE CD4 and mouse A alpha chain is required for the clonal deletion. PMID- 1899098 TI - Regulation of MHC class II antigen expression. Opposing effects of tumor necrosis factor-alpha on IFN-gamma-induced HLA-DR and Ia expression depends on the maturation and differentiation stage of the cell. AB - MHC class II induction by cytokines has been suggested to play a major role in the initiation and propagation of immune and autoimmune processes. TNF-alpha has been found both to enhance and also to inhibit IFN-gamma-induced MHC class II expression. In the present studies, the effect of TNF-alpha on IFN-gamma induced MHC class II expression was tested in various cell lines. On the basis of the data, we propose that, depending on the stage of differentiation and maturation of the cells, TNF-alpha might synergize or antagonize the affects of IFN-gamma on the regulation of MHC class II expression. Thus, in immature cells such as HL-60 or THP-1, TNF-alpha enhances IFN-gamma-induced class II expression. However, when differentiation was induced in these cells by TPA or IFN-gamma, the additive effect of TNF-alpha on the IFN-gamma induced DR expression was eliminated. Furthermore, TNF-alpha down-regulates the IFN-gamma-induced class II expression in differentiated cells such as human skin fibroblasts or activated macrophages. In bone marrow cells induced to differentiate in vitro, TNF-alpha decreased the IFN-gamma-induced MHC class II expression in a maturation-dependent fashion. These results provide a rational explanation for the conflicting reports regarding the effect of TNF-alpha on IFN-gamma-induced class II expression. But more importantly they may be relevant to the biologic function of TNF-alpha. Thus, we show that TNF-alpha-treated mice have reduced level of Ia expression on peritoneal macrophages and in vivo treatment with TNF-alpha antagonizes the ability of IFN-gamma to induce class II expression on these macrophages. PMID- 1899099 TI - Absence of preferential homologous H/L chain association in hybrid hybridomas. AB - Bispecific mAb contain two Ag-combining sites each composed of a different combination of H and L chains. The resulting ability to react with and cross-link two different Ag makes these molecules a novel tool for application in biology and medicine. Intact bispecific mAb can be made only by biologic means, e.g., by fusion of two established hybridomas. Appropriate assembly of bispecific mAb by these hybrid cells depends on H = L chain behavior: strong preferential homologous H-L pairing would benefit the yield of bispecific antibodies. We have analyzed the Ig species produced by eight hybrid hybridomas (quadromas). Quadroma produced IgG was fractionated and characterized for H and L chain content. The Ag reactivities were verified by using ELISA and immunofluorescence. Preferential homologous pairing was seen only with a minority of H-L chain pairs; L chains associated on average in a random fashion with H chains. This indicates that in the B cells from which the parental hybridomas were obtained, no strong selection had occurred on H-L recombination. Our results extend recent biochemical competitive H-L reassociation experiments, where on average an at random association of L chains with H chains was found; evidently this random association occurs in our biologic system as well. For the biologic production of bispecific antibodies this means that only in a small number of cases the "ideal" producer will be met. From the viewpoint of generation of antibody diversity, our results favor a large freedom for combinatorial binding of H and L chains during B cell ontogeny. PMID- 1899100 TI - Differences in human immunodeficiency virus type 1 (HIV-1) anti-p24 reactivities in serum of HIV-1-infected and uninfected subjects: analysis of indeterminate western blot reactions. AB - Anti-p24 reactions in sera from 42 human immunodeficiency virus type 1 (HIV-1) infected and 36 uninfected people with indeterminate Western blot antibody tests for HIV-1 were studied. Anti-p24 reactivity in HIV-1-infected people was completely blocked by HIV-1 recombinant p24 antigen, whereas the reaction in uninfected individuals with indeterminate patterns was inhibited partly or not at all. In contrast to infected individuals, anti-p24 reactivity from uninfected individuals could not be detected by an inhibition ELISA for HIV-1 p24 antibody. These results suggest a practical way to distinguish anti-p24 reactivity in sera from patients with HIV-1 infection from that seen in uninfected patients with indeterminate Western blot reactions. PMID- 1899101 TI - Induction of vascular injury by Pseudomonas aeruginosa cytotoxin in rabbit lungs is associated with the generation of different leukotrienes and hydroxyeicosatetraenoic acids. AB - Pseudomonas aeruginosa cytotoxin, a transmembrane pore-forming protein, causes an increase in pulmonary microvascular permeability with subsequent lung edema formation, possibly related to the induction of arachidonic acid (AA) lipoxygenase products. To investigate this, isolated rabbit lungs were perfused with cytotoxin-containing buffer (6.5 and 13 micrograms of toxin/ml). A severalfold increase in the capillary filtration coefficient was induced, both preceded and accompanied by a marked time- (15-60 min) and dose-dependent release of cysteinyl leukotrienes (LT), LTB4, and 5-, 12-, and 15-hydroxyeicosatetraenoic acids (HETEs) into the lung perfusate. In the bronchoalveolar lavage fluid, corresponding AA-derived products were detected; the total sum of HETEs surpassed that of cysteinyl LTs in this compartment. The lipoxygenase inhibitors AA861 (10 microM) and nordihydroguaiaretic acid (100 microM) and EGTA (5 mM) suppressed the intravascular and alveolar liberation of all 5-lipoxygenase-derived AA metabolites, paralleled by a marked reduction and retardation of microvascular permeability increase (AA861). It thus seems that Pseudomonas cytotoxin induces generation of LTs and HETEs in rabbit lungs that may contribute to the development of pulmonary microvascular injury evoked by this bacterial agent. PMID- 1899102 TI - Preferential utilization of specific immunoglobulin heavy chain diversity and joining segments in adult human peripheral blood B lymphocytes. AB - We have examined at the molecular level the CDR3 and adjacent regions in peripheral blood B lymphocytes of normal individuals. A total of 111 sequences (12-28 sequences from six individuals) were obtained after cloning of the polymerase chain reaction-amplified segments into plasmids or phage. The average length of the VDJ joining was 109 nucleotides, with a range from 79 to 151. Approximately 75% of the sequences were in frame when translated into amino acids. Among the JH segments, JH4 was found most frequently (in 52.5% of the sequences), and JH1 and JH2 segments the least frequently (approximately 1% of the clones). A polymorphic JH6 gene with a one-codon deletion accompanied by a base change was present in two of six patients. Preferential breakpoints were found for JH2, JH3, JH4, and JH5, although the breakpoints of JH6 were distributed more heterogenously. In approximately 90% of the cases, significant homology of the D regions with published D sequences was found. Preferential usage of a particular coding frame was observed in in-frame sequences utilizing DA, D21/9, and DM1 segments. However, in general, all coding frames of germline D genes were used to generate CDR3s. Eight sequences that have a DN1-like D sequence with two base changes at the same positions were identified, suggesting the likely existence of a new germ line D gene belonging to the DN families. Using probes specific for a particular CDR3, the frequency of a specific B cell clone in the peripheral blood of normal individuals was estimated to be at most as high as 1/20,000. PMID- 1899103 TI - 5' regulatory region of a novel cytokine gene mediates selective activation by interferon gamma. AB - A newly described member of the platelet factor 4 family of cytokine genes, mig, is selectively induced by interferon gamma (IFN-gamma), and not IFN-alpha, in the mouse macrophage-like cell line RAW 264.7. Treatment of RAW 264.7 cells with IFN gamma activated mig gene transcription as determined by nuclear run-on assays. mig genomic clones were isolated, and constructs containing genomic fragments that included the mig promoter region and the CAT reporter gene were prepared. In RAW 264.7 cells transfected with these constructs, CAT activity was found to be selectively induced by IFN-gamma. A 278-bp genomic fragment containing 235 nucleotides 5' of the transcription start site was sufficient for IFN-gamma selective induction of CAT activity. Analysis of 5' deletion mutants localized a region essential for activation by IFN-gamma to within 64 nucleotides extending from -235 to -172. A genomic fragment containing this sequence was capable of conferring IFN-gamma inducibility to constructs with a heterologous promoter. PMID- 1899104 TI - Somatic mutations in the variable regions of a human IgG anti-double-stranded DNA autoantibody suggest a role for antigen in the induction of systemic lupus erythematosus. AB - The processes that govern the generation of pathogenic anti-DNA autoantibodies in human systemic lupus erythematosus (SLE) are largely unknown. Autoantibodies may arise as a consequence of polyclonal B cell activation and/or antigen-driven B cell activation and selection. The role of these processes in humoral autoimmunity may be studied by molecular genetic analysis of immunoglobulin (Ig) variable (V) regions of antibodies that are characteristic of SLE. We have analyzed the gene elements that encode a high affinity, IgG anti-double-stranded DNA autoantibody secreted by a monoclonal Epstein-Barr virus (EBV)-transformed cell line derived from a patient with active SLE. In addition, we have identified, cloned, and sequenced the germline counterparts of the VH and VL genes expressed in this autoantibody. The comparison of both sets of gene elements shows that the autoantibody VH and VL regions harbor numerous somatic mutations characteristic of an antigen-driven immune response. The light chain expressed in this autoantibody is a somatically mutated variant of the kv325 germline gene that is frequently associated with paraproteins having autoantibody activity and with Ig molecules produced by malignant B cells that express the CD5 antigen. Furthermore, the utilized DH segment has been repeatedly found in multireactive, low affinity IgM anti-DNA autoantibodies from SLE patients and healthy individuals. These results suggest that pathogenic IgG anti-DNA autoantibodies in human SLE may arise through antigen-driven selection of somatic mutations in the gene elements that frequently encode multireactive IgM autoantibodies. PMID- 1899105 TI - Anti-CD4 mediates clonal anergy during transplantation tolerance induction. AB - Depletion of CD4+ cells using anti-CD4 monoclonal antibodies leads to allograft tolerance. Here we show that anti-CD4-mediated tolerance to pancreatic islets of Langerhans transplanted from an A/J (IEk) donor to a diabetic C57B1/6 (B6) (IE-) recipient occurs in the absence of clonal deletion of the potentially IE-reactive V beta 11+ T cells. Instead, a state of clonal anergy is induced in both the CD4+V beta 11+ and CD8+V beta 11+ T cell subsets. This clonal anergy can be partially overcome in vitro by the addition of recombinant interleukin 2. PMID- 1899106 TI - Interleukin 10: a novel stimulatory factor for mast cells and their progenitors. AB - We have characterized the mast cell stimulating activity of murine cytokine synthesis inhibitory factor, referred to as interleukin 10 (IL-10). It was found that IL-10 alone failed to support the growth of mast cell lines and mast cell progenitors. Nevertheless, it dramatically enhanced their growth when combined with IL-3 or IL-4. Moreover, IL-4 plus IL-10 supported the proliferation of mast cells as well as IL-3, suggesting that these two factors may provide a pathway for their development independent of IL-3. However, optimal mast cell growth was stimulated by the combination of IL-10, IL-4, and IL-3. This particular set of cytokines are coordinately produced by activated T cells and may constitute an effective network regulating early and late stages of mast cell development during certain immune responses. PMID- 1899107 TI - Autonomous growth and tumorigenicity induced by P40/interleukin 9 cDNA transfection of a mouse P40-dependent T cell line. AB - To test the transforming potential of deregulated P40/Interleukin 9 expression, we transfected a mouse P40-dependent T cell line with P40 cDNA, and examined the tumorigenicity of the resulting transfectants. When the cells, which grew autonomously in vitro, were injected intraperitoneally or subcutaneously into syngeneic mice, a very high tumor incidence was observed with as few as 10(4) cells per inoculum. Animals died as a result of widespread dissemination of lymphomatous tissue to abdominal and thoracic organs. The same P40-dependent cell line transfected with a control construct did not form tumors even after injection of 10(7) cells. These results indicate that uncontrolled expression of P40 can support T cell proliferation in vivo, and may be a transforming event involved in the development of certain T cell tumors. PMID- 1899108 TI - Proteolytic cleavage of the Alzheimer's disease amyloid A4 precursor protein. AB - Amyloid A4 protein (beta-protein) is deposited in the brain of a patient with Alzheimer's disease (AD) as one of the main components of extracellular cerebrovascular amyloid, as well as neurofibrillary tangles. It is derived from a precursor protein, and its formation has been considered to be a rate-limiting step for brain degeneration in AD. In this article, proteolytic cleavage events that can degrade amyloid precursor protein are reviewed with respect to how the topographical distribution of the proteinase and its substrates disturbs normal processing steps in AD brain. PMID- 1899109 TI - Neurotensin regulation of endogenous acetylcholine release from rat striatal slices is independent of dopaminergic tone. AB - The effects of neurotensin (NT) alone or in combination with the dopamine antagonist sulpiride were tested on the release of endogenous acetylcholine (ACh) from striatal slices. NT enhanced potassium (25 mM)-evoked ACh release from striatal slices in a dose-dependent manner. This effect was tetrodotoxin insensitive, suggesting an action directly on cholinergic elements. The dopamine antagonist sulpiride (5 x 10(-5) M) significantly increased (63%) potassium evoked ACh release from striatal slices; potassium-evoked ACh release was further increased (90%) in the presence of NT (10(-5) M) and sulpiride (5 x 10(-5) M). The second set of experiments tested the effects of 6-hydroxydopamine (6-OHDA) lesions of the substantia nigra on NT-induced increases of potassium-evoked ACh release. These lesions did not alter the NT regulation of potassium-evoked ACh release from striatal slices, but did significantly increase spontaneous (33%) and potassium-evoked (40%) ACh release from striatal slices. Striatal choline acetyltransferase activity was not affected by 6-OHDA lesions. In addition, following 6-OHDA lesions, sulpiride was ineffective in altering ACh release from striatal slices. Furthermore, evoked ACh release in the presence of the combination of NT and sulpiride was not different from that in the presence of NT alone. These results suggest that in the rat striatum, NT regulates cholinergic interneuron activity by interacting with NT receptors associated with cholinergic elements. Moreover, the NT modulation of cholinergic activity is independent of either an interaction of NT with D2 dopamine receptors or the sustained release of dopamine. PMID- 1899111 TI - Myeloablative combination chemotherapy without total body irradiation for neuroblastoma. AB - Myeloablative treatment intensification in 25 patients diagnosed when older than 12 months of age with stage IV neuroblastoma included sequential delivery of cisplatin 120 mg/m2 x 1, hyperfractionated radiation (2,100 cGy) to the primary site and adjacent lymph nodes, carmustine (BCNU) 200 mg/m2 x 1, melphalan 60 mg/m2/d x 3 (n = 13) or thiotepa 300 mg/m2/d x 3. (n = 12), and etoposide (VP 16) 300 mg/m2/d x 3. Seventy-two hours after the last dose of VP 16, histologically tumor-free and 4-hydroperoxycyclophosphamide (4-HC; 100 mumol/L)-purged autologous bone marrow (ABMT) was infused. Acute toxicities included grade 3 to 4 oral mucositis, grade 1 to 2 diarrhea, and fevers. No patient required infusion of unpurged reserve autografts. At ABMT, 16 patients (group I) were progression free 6.5 months to 14 months (median, 9 months) from diagnosis: seven remain progression-free 20 months to 46 months (median, 39 months) off therapy, six relapsed 4 months to 17 months post-ABMT, and three died of toxicity (candidiasis, metabolic derangement, and venoocclusive disease [VOD]). The event free survival of group I patients is 44% at 24 months post-ABMT. Nine patients (group II) were in second remission at ABMT, including three who had relapsed after other transplant procedures: two are progression-free 24 months and 41 months off therapy, four relapsed 3 months to 12 months post-ABMT, and three died of toxicity (aspergillosis, hemorrhagic cystitis, VOD). Only one of 10 relapses involved a primary site, suggesting a beneficial effect of local radiation. In terms of survival or toxicity, an advantage for melphalan or thiotepa was not evident. Regimens such as this may prolong the survival of selected patients with poor-risk neuroblastoma, but concerns over late relapses and toxicity mandate continuing efforts to devise alternative, less risky, and more clearly beneficial approaches for definitive ablation of neuroblastoma. PMID- 1899110 TI - Elevation of taurine in hippocampal extracellular fluid and cerebrospinal fluid of acutely hypoosmotic rats: contribution by influx from blood? AB - Previous work has demonstrated that there is a selective increase in extracellular taurine in the brain during acute water intoxication. One aim of the present study was to investigate whether plasma taurine contributes to this increase. To this end, the concentrations of taurine, other amino acids, and ethanolamine (EA) were measured in plasma and CSF of urethane-anesthetized rats injected with 150 ml/kg body weight of distilled water. Blood pressure, blood gases, and pH, as well as plasma and CSF osmolality, were also measured. The CSF level of albumin was quantitated to study the function of the blood-CSF barrier. In separate experiments, hippocampal microdialysis was performed to determine the effects of acute plasma hypoosmolality on extracellular amino acids. Finally, the effect of water injection on hippocampal specific gravity and tissue amino acids was assessed. Blood gases and pH were essentially unchanged after water administration. Mean arterial blood pressure increased to peak levels approximately 50 mm Hg above control. Plasma osmolality decreased rapidly, whereas the depression of CSF osmolality was slower and less pronounced. The average volume of the hippocampus increased by 8%. Water injection was accompanied by a 25-fold elevation of taurine in plasma, whereas phosphoethanolamine (PEA) and EA increased moderately. A small fraction of the increase in plasma taurine might derive from blood cells because dilution of blood in vitro led to doubled plasma levels of the amino acid. Taurine, PEA, and EA increased consistently in CSF and hippocampal microdialysates. Plasma hypoosmolality transiently opened the blood-CSF barrier is reflected by augmented CSF concentrations of albumin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1899112 TI - Comparison of oxine and tropolone methods for labeling human platelets with indium-111. AB - The effect of the chelates oxine and tropolone, used to label platelets, on the kinetics of indium-111-(111In) labeled platelets was studied in twelve normal human subjects. Autologous platelets were labeled either in saline with 111In oxine or in plasma with 111In-tropolone. Mean platelet lifespan was estimated by fitting the disappearance curve of platelets from the circulation to the multiple hit and other mathematical models. The in vivo distribution of platelets was quantitatively imaged with a scintillation camera. The in vivo recovery of 111In oxine and 111In-tropolone did not differ, and the mean platelet lifespan was also similar (111In-oxine: 230 +/- 29 hr; 111In-tropolone: 226 +/- 13 hr). At equilibrium (90 min after reinjection of labeled platelets) and at the end of platelet lifespan, 111In-oxine and 111In-tropolone radioactivities in the spleen and liver were similar. These results demonstrate that the results of kinetics measured with 111In-oxine or 111In-tropolone do not differ significantly. PMID- 1899113 TI - Selective 2-[18F]fluorodopa uptake for melanogenesis in murine metastatic melanomas. AB - The relationship between 3,4-dihydroxy-2-[18F]fluoro-L-phenylalanine (2 [18F]FDOPA) uptake and melanogenesis was studied using mice bearing two B16 melanomas: B16-F1 has a higher melanin synthesis ability and a slower growing rate than the higher metastatic B16-F10. A significantly higher 2-[18F]FDOPA uptake by B16-F1 than by B16-F10 and a reverse relationship for the uptake of [14C] 2-deoxy-2-fluoro-D-glucose and [3H]thymidine were observed 1 hr postinjection. F1-to-F10 ratios of both the 2-[18F]FDOPA uptake and the acid insoluble radioactivity increased to about 5 at 6 hr, which paralleled the melanin content. FM3A mammary carcinoma showed a 2-[18F]FDOPA uptake similar to the B16-F10 but without the acid-insoluble radioactivity. With D,L-DOPA loading, a 55% decreased uptake by FM3A 1 hr postinjection was significantly greater than the 20% reduction in both melanomas. O-Methylated 2-[18F]FDOPA was a predominant acid-soluble metabolite in all tumors. Whole-body autoradiography discriminated the two melanomas clearly. 2-[18F]FDOPA may be a promising tracer for the selective imaging of melanogenesis. PMID- 1899115 TI - Voltage clamp analysis reveals multiple populations of quanta released at neuromuscular junctions of rats treated with 2,4-dithiobiuret. AB - Rats treated with small daily doses of 2,4-dithiobiuret (DTB) develop a delayed onset neuromuscular weakness after 4-6 days of treatment. Analysis of quantal release using nerve-muscle preparations taken from rats exhibiting neuromuscular weakness demonstrated a decrease in quantal content of evoked end-plate potentials (EPP), a decrease in the frequency of spontaneously occurring miniature end-plate potentials (MEPP) and a prolongation of rise and decay times for MEPPs. This latter effect is also observed in muscles taken from rats after one large dose of DTB; in which no weakness is observed. Moreover, an increase in the incidence of abnormally large amplitude MEPPs has also been observed after both acute and chronic treatment of rats with DTB. The purpose of the present study was to determine whether the observed prolongation of rise and decay times for the spontaneous synaptic events observed after exposure to DTB can be attributed to a generalized slowing of all synaptic events or whether DTB causes an increase in a distinct population of abnormal synaptic events. End-plate currents and miniature end-plate currents (MEPC) were recorded, using two microelectrode voltage clamp, from hemidiaphragm preparations of rats after acute administration of 25 mg/kg and chronic treatment with 1 mg/kg/day (7-8 days) DTB. Mean MEPC amplitude calculated for all MEPCs was unaffected by DTB treatment; however there was an increase in the incidence of giant MEPCs after both acute and chronic treatments.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1899114 TI - Quinidine inhibits prolactin secretion induced by thyrotropin-releasing hormone, high medium potassium or hyposmolarity in GH4C1 cells. AB - In cultured GH4C1 cells quinidine inhibited basal prolactin (PRL) secretion and that induced by 0.1 to 10 nM thyrotropin-releasing hormone (TRH), 30 mM medium K+ or 30% medium hyposmolarity but did not inhibit secretion induced by 100 nM 12-O tetradecanoylphorbol 13-acetate. Inhibition of basal PRL secretion was highly correlated with the drug concentration between 30 microM to 1 mM quinidine; 50% inhibition of basal secretion occurred at 300 microM and at this concentration quinidine completely blocked PRL secretion stimulated by TRH, K+ and hyposmolarity. Significant inhibition of TRH-induced PRL secretion was produced by 15 microM quinidine, a concentration equivalent to that in plasma during standard antiarrhythmic therapy with quinidine in humans. In rats in vivo, a single injection of 2 mg i.p. of quinidine gluconate/100 g b.wt. 1 hr before TRH injection significantly inhibited induced TSH secretion by 15%. Quinidine inhibition of secretion may be caused by blocking depolarization of the cell membrane, thus depressing voltage-gated Ca++ channels and preventing a rise in intracellular Ca++ release. PMID- 1899116 TI - Chiral recognition of pinacidil and its 3-pyridyl isomer by canine cardiac and smooth muscle: antagonism by sulfonylureas. AB - Pinacidil, a potassium channel opener (PCO), relaxes vascular smooth muscle by increasing potassium ion membrane conductance, thereby causing membrane hyperpolarization. PCOs also act on cardiac muscle to decrease action potential duration (APD) selectively. To examine the enantiomeric selectivity of pinacidil, the stereoisomers of pinacidil (a 4-pyridylcyanoguanidine) and its 3-pyridyl isomer (LY222675) were synthesized and studied in canine Purkinje fibers and cephalic veins. The (-)-enantiomers of both pinacidil and LY222675 were more potent in relaxing phenylephrine-contracted cephalic veins and decreasing APD than were their corresponding (+)-enantiomers. The EC50 values for (-)-pinacidil and (-)-LY222675 in relaxing cephalic veins were 0.44 and 0.09 microM, respectively. In decreasing APD, the EC50 values were 3.2 microM for (-) pinacidil and 0.43 microM for (-)-LY222675. The eudismic ratio was greater for the 3-pyridyl isomer than for pinacidil in both cardiac (71 vs. 22) and vascular (53 vs. 17) tissues. (-)-LY222675 and (-)-pinacidil (0.1-30 microM) also increased 86Rb efflux from cephalic veins to a greater extent than did their respective optical antipodes. The antidiabetic sulfonylurea, glyburide (1-30 microM), shifted the vascular concentration-response curve of (-)-pinacidil to the right by a similar extent at each inhibitor concentration. Glipizide also antagonized the response to (-)-pinacidil, but was about 1/10 as potent with a maximal shift occurring at 10 and 30 microM. Glyburide antagonized the vascular relaxant effects of 0.3 microM (-)-LY222675 (EC50, 2.3 microM) and reversed the decrease in APD caused by 3 microM (-)-LY222675 (EC50, 1.9 microM). Nitroprusside did not alter 86Rb efflux, and vascular relaxation induced by sodium nitroprusside was unaffected by sulfonylureas. Thus, the enantiomers of the 3 pyridyl isomer of pinacidil demonstrate enhanced stereospecificity in both canine cardiac and vascular tissues compared to the enantiomers of pinacidil. However, the relative selectivity of pinacidil and its 3-pyridyl isomer for cardiac and vascular smooth muscle remains unaltered. Sulfonylureas antagonize the more potent enantiomers in both tissues, supporting the involvement of an ATP sensitive potassium channel in the action of PCOs; however, antagonism in canine vascular smooth muscle by sulfonylureas does not resemble classical competitive antagonism. PMID- 1899117 TI - 5-HT2 antagonists stereoselectively prevent the neurotoxicity of 3,4 methylenedioxymethamphetamine by blocking the acute stimulation of dopamine synthesis: reversal by L-dopa. AB - The active and inactive stereoisomers of the serotonin (5-HT2) antagonist, MDL 11,939, were used to examine the relationship between the acute effects of 3,4 methylenedioxymethamphetamine (MDMA) on the dopaminergic system and its long-term effects on the serotonergic system. Only the R-(+) stereoisomer of MDL 11,939 both reversed the acute stimulation of striatal dopamine synthesis by MDMA and prevented the deficit in forebrain 5-HT concentrations measured one week later. This acute activation of striatal dopamine synthesis by MDMA is a compensatory response to the carrier-mediated efflux of transmitter as shown by its sensitivity to the dopamine uptake inhibitor, nomifensine. It is suggested that in the absence of this enhanced synthesis, the dopaminergic neuron cannot sustain the carrier-mediated dopamine release which is a prerequisite for the development of MDMA-induced neurotoxicity. This hypothesis is supported by the observation that the administration of the dopamine precursor, L-dopa, with MDMA reverses the protective effects of 5-HT2 receptor antagonists. PMID- 1899118 TI - Differential hemodynamic effects and tolerance properties of nitroglycerin and an S-nitrosothiol in experimental heart failure. AB - S-nitrosothiols are potent in vitro vasodilators, but little is known about their in vivo action. In this study, we compared the effects of S-nitroso N-acetyl penicillamine (SNAP) and nitroglycerin (NTG) on left ventricular (LV) hemodynamics in congestive heart failure rats. By using a twoday crossover design, stepwise i.v. infusions of SNAP or NTG at 3, 5 and 8 micrograms/min were administered for 30 min each, followed by a dose of 10 micrograms/min over the next 10 h. LV end-diastolic and peak-systolic pressures (LVEDP and LVPSP, respectively) were measured at selected intervals. SNAP and NTG produced maximal LVEDP reductions of 46 and 44%, respectively, at the highest infusion rate. However, at the lower doses, greater reductions of LVEDP were seen with SNAP. NTG had a smaller effect on LVPSP (maximum 6% reduction) than SNAP (maximum reduction of 15%). During the 10-h infusion of NTG, LVEDP gradually returned to base-line values, indicating the development of tolerance, despite relatively constant plasma levels of NTG over the infusion period. Tolerance in LVEDP effects was not observed during the 10-h infusion of SNAP. In the presence of NTG tolerance, rats were still responsive to SNAP (mean reduction of LVEDP 24%), suggesting the absence of cross-tolerance between these two nitrovasodilators. These results suggest that SNAP is a more potent in vivo vasodilator than NTG, has more arterial action than NTG and is less prone to produce LV hemodynamic tolerance. PMID- 1899119 TI - Persistent effects of interleukin-1 on smooth muscle preparations from adrenalectomized rats: implications for increased phospholipase-A2 activity via stimulation of 5-lipoxygenase. AB - Human recombinant interleukin-1 beta (hrIL-1 beta) potentiated CaCl2-induced contractions of isolated stomach strip preparations from adrenalectomized rats (ADXSS). Associated with this effect were increased prostaglandin E2 and peptidyl leukotriene (LT) synthesis. Unlike preparations from normal rat stomach strips or sham-operated animals, tissue responses and eicosanoid production of ADXSS failed to return to pre-hrIL-1 beta control levels after washout of the interleukin, these effects being abrogated by the lipoxygenase inhibitor nordihydroguaiaretic acid. Additionally, the LTD4 antagonist FPL55712 also prevented the increase in contraction and prostaglandin E2 synthesis caused by hrIL-1 beta without decreasing peptidyl LT synthesis. In separate experiments, hrIL-1 beta failed to increase the recovery of arachidonic acid-induced contractions after aspirin pretreatment in both ADXSS and rat stomach strips. The data indicate that the effects caused by hrIL-1 beta on ADXSS are possibly the result of an exacerbated phospholipase A2 activity particularly inasmuch as increases in cellular cyclooxygenase synthesis are unlikely in this experimental system. It appears likely that a peptidyl LT is involved in this process. Elevation of phospholipase A2 activity by interleukin-1 like drugs may be an important factor limiting the use of these agents as adjuvants particularly in patients with low blood glucocorticoid levels. PMID- 1899120 TI - High affinity [3H]glibenclamide binding sites in rat neuronal and cardiac tissue: localization and developmental characteristics. AB - We examined the binding of the antidiabetic sulfonylurea [3H] glibenclamide to rat brain and heart membranes. High affinity binding was observed in adult rat forebrain (Kd = 137.3 pM, maximal binding site density = 91.8 fmol/mg of protein) and ventricle (Kd = 77.1 pM, maximal binding site density = 65.1 fmol/mg of protein). Binding site density increased approximately 250% in forebrain membranes during postnatal development but was constant in ventricular membranes. Quantitative autoradiography was used to examine the regional distribution of [3H] glibenclamide binding sites in sections from rat brain, spinal cord and heart. The greatest density of binding in adult brain was found in the substantia nigra and globus pallidus, whereas the other areas displayed heterogenous binding. In agreement with the membrane binding studies, 1-day-old rat brain had significantly fewer [3H]glibenclamide binding sites than adult brain. Additionally, the pattern of distribution of these sites was qualitatively different from that of the adult. In adult rat spinal cord, moderate binding densities were observed in spinal cord gray and displayed a rostral to caudal gradient. In adult rat heart, moderate binding densities were observed and the sites were distributed homogeneously. In conclusion, significant development of [3H]glibenclamide binding sites was seen in the brain but not the heart during postnatal maturation. Furthermore, a heterogeneous distribution of binding sites was observed in both the brain and spinal cord of adult rats. PMID- 1899121 TI - Inhibition of endothelium-dependent relaxations by phorbol myristate acetate in canine coronary arteries: role of a pertussis toxin-sensitive G-protein. AB - Activation of protein kinase C by phorbol esters inhibits the endothelium dependent relaxations evoked by certain stimuli. The release of endothelium derived relaxing factor can be evoked by a number of distinct subcellular processes, including activation of a pertussis toxin-sensitive G-protein. The aim of the present study was to determine whether or not the inhibitory effect of phorbol esters on endothelial function was associated with inhibition of the pertussis toxin-sensitive pathway. Rings of canine coronary artery were suspended for isometric tension recording in organ chambers filled with modified Krebs Ringer bicarbonate solution, gassed with 95% O2-5% CO2 (37 degrees C). Treatment of arterial rings with pertussis toxin (100 ng/ml) or with phorbol myristate acetate (PMA, 10(-8) M) inhibited the endothelium-dependent relaxations produced by UK 14,304, an alpha-2 adrenergic agonist, leukotriene C4 or by NaF, a direct activator of G-proteins, but did not affect the endothelium-dependent relaxations produced by bradykinin or by A23187. If the arterial rings were first treated with pertussis toxin, PMA (10(-8) M) no longer inhibited the endothelium dependent relaxations to NaF. Increasing the concentration of PMA (to 3 X 10(-8) and 10(-7) M) caused inhibition of responses to bradykinin. At higher concentrations, PMA (3 X 10(-7) and 10(-6)) also inhibited the relaxations evoked by A23187. The endothelium-independent relaxations evoked by nitroglycerin were not affected by PMA (10(-8) to 10(-6)).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1899122 TI - The effect of suramin, tumor necrosis factor and interferon gamma on human prostate carcinoma. AB - Suramin, an antiparasitic agent which has been shown to block the stimulatory effect of growth factors on certain cancers, is currently being evaluated in clinical trials and as an antineoplastic agent in patients with advanced prostate carcinoma. Preliminary studies suggested that suramin inhibits the growth in vitro of human prostate carcinoma. The present study was performed in order to evaluate the effect of suramin, recombinant human tumor necrosis factor (TNF), interferon gamma and the combination of suramin plus TNF or interferon gamma on proliferation of PC-3, a human, hormone unresponsive prostate carcinoma cell line. In medium containing 2% fetal calf serum (FCS) suramin, at doses of 10 microM, 30 microM and 100 microM (levels readily achievable in humans) inhibited proliferation of PC-3. TNF, at a concentration of 500 units/ml., induced an approximately 50% inhibition of growth of PC-3. The combination of suramin plus TNF induced a greater inhibition of growth than did either agent alone, even at the low dose of 10 microM suramin. Interferon gamma, 500 units/ml., inhibited PC 3 growth. However, the combination of interferon gamma plus suramin (30 microM) induced less inhibition of proliferation than did interferon gamma alone. These results may serve as a rationale for clinical trials employing the combination of TNF plus suramin in patients with advanced prostate carcinoma. PMID- 1899123 TI - Decreased dopaminergic control of prolactin secretion in male obesity: normalization by fasting. AB - To test whether short-term fasting has a different effect on hormone release from lactotrophs and thyrotrophs in normal-weight men compared with obese men, 10 mg metoclopramide (MET) was administered orally to seven normal and six obese men before and after a 56-hour fast. In the normal subjects, MET raised the serum prolactin (PRL) level before fasting from 5.1 +/- 1.3 to 58.6 +/- 9.5 micrograms/L in 60 minutes (P less than .02), but left the thyrotropin (TSH) level unaffected. An almost identical hormone response was seen after fasting. Obese men responded differently. Their lactotrophs were initially refractory to MET stimulation (PRL increase from 9.5 +/- 5.1 to 17.5 +/- 5.7 micrograms/L, NS), but became sensitive to such stimulation after fasting (PRL increase from 8.2 +/- 4.5 to 46.3 +/- 6.7 micrograms/L, P less than .01). The thyrotrophs were unaffected by MET before, as well as after, the fast. Although decreased PRL synthesis, reduced cell membrane permeability, and inadequate MET stimulation are plausible mechanisms by which the reduced PRL responsiveness to MET could be explained in the obese patients, neither is likely in view of the fact that the lactotrophs responded promptly to thyrotropin-releasing hormone (TRH), administered intravenously (IV) 60 minutes after MET, in the fed obese patients (PRL increase after TRH from 17.5 +/- 5.7 to a maximum of 48.0 +/- 8.7 micrograms/L, P less than .05). Furthermore, a 50% reduction of the MET dose (5 mg) resulted in a significant PRL response in non-obese healthy men (PRL increase from 3.1 +/- 1.1 to 40.3 +/- 0.9 micrograms/L, P less than .001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1899125 TI - Heterosexual gonorrhoea in central Sydney: implications for HIV control. AB - Gonorrhoea is a sexually transmissible disease (STD) characteristic of a core group of individuals and their contacts. From the experience of a Sydney STD clinic, as well as local and national population-based reports, trends in heterosexually acquired gonorrhoea in Australia over a decade were examined. An overall decline of 90% in case numbers between 1981 and 1989 was found, with an average yearly decline of 30%. The improved compliance with condom use by Sydney prostitutes and their clients could have been a major factor. This occurred in an environment of peer and public education about AIDS and the decriminalisation of prostitution. Improved health professional training and public access to specialist STD services against a background of demographic changes may also have contributed. However a persistent "seeding" of penicillinase-producing strains of gonorrhoea from Southeast Asia through men not using condoms was detected. These data have potential implications for the importation of heterosexually acquired human immunodeficiency virus infection into Australia. PMID- 1899124 TI - Sulfonylureas activate glucose transport and protein kinase C in rat adipocytes. AB - Glyburide and tolbutamide, at concentrations of 20 to 40 mumol/L and 1 to 2 mmol/L, respectively, stimulated glucose transport in rat adipocytes. Concomitantly, protein kinase C was activated, as evidenced by translocation of immunoreactive enzyme from cytosol to membranes. Glucose transport effects of the sulfonylureas were blocked by three inhibitors of protein kinase C (H-7, staurosporine, and sangivamycin), and by phorbol ester-induced down-regulation of protein kinase C. These findings suggest that sulfonylureas may stimulate glucose transport in rat adipocytes through activation of protein kinase C. PMID- 1899126 TI - Cost comparison of intravenous antibiotic administration. PMID- 1899129 TI - Reye syndrome surveillance--United States, 1989. AB - Reye syndrome (RS) is an acute illness that occurs almost exclusively in children; it is characterized clinically by profuse vomiting and neurologic dysfunction, sometimes progressing to delirium, coma, and death. Continuous national surveillance for RS was established in December 1976. This report summarizes RS cases for the 1989 surveillance year (December 1, 1988-November 20, 1989). PMID- 1899128 TI - Rotavirus surveillance--United States, 1989-1990. AB - Rotavirus infection is the most common cause of dehydrating diarrhea in children in the United States. In January 1989, CDC established a National Rotavirus Surveillance System (NRSS) to monitor national patterns in the epidemiology of rotavirus. This report summarizes findings from the NRSS from January 1989 through November 1990. PMID- 1899127 TI - Alternative case-finding methods in a crack-related syphilis epidemic- Philadelphia. AB - Use of crack cocaine and exchange of drugs for sex have been identified as substantial contributors to the syphilis epidemic in Philadelphia and other locations in the United States. In Philadelphia, from 1985 through 1989, the number of reported cases of early syphilis (primary, secondary, and early latent stages) increased 551%, from 696 to 4528 cases per year. Among 2473 persons with early syphilis interviewed by the Philadelphia Department of Public Health (PDPH) from January through July 1990, 48% reported they or a sex partner used crack cocaine, and 31% reported exchanging drugs or money for sex (not all of those interviewed answered both questions). Traditional approaches to the control of syphilis that emphasize partner notification have not been effective in halting this epidemic. The partner notification approach requires public health workers to identify sex partners of a person with a sexually transmissible disease (e.g., syphilis) and then to contact these sex partners to provide examination and curative or preventive treatment. However, because persons who are involved in the exchange of drugs and/or money for sex often cannot or will not provide sufficient information about sex partners to enable public health authorities to locate those partners (2,4,5), alternative case-finding methods are needed. This report describes efforts by the PDPH to identify persons infected with Treponema pallidum by using serologic screening at locations where crack cocaine is used. PMID- 1899130 TI - Micronucleus assay protocols. PMID- 1899131 TI - Acrylamide is genotoxic to the somatic and germ cells of Drosophila melanogaster. AB - The genotoxic effects of acrylamide, a recently detected carcinogen, have been studied in the somatic (wing primordia) and germ cells of Drosophila melanogaster by the wing mosaic assay and the sex-linked recessive lethal test respectively. Larvae, 72 +/- 4 h old, were exposed to 6 different concentrations of acrylamide ranging between 0.25 mM and 5.0 mM in instant medium for 48 h. It is observed that acrylamide is both mutagenic and recombinogenic in the wing disc cells and induces sex-linked recessive lethals. PMID- 1899133 TI - Medical condition, nursing condition, nursing intensity, medical severity, and length of stay in hospitalized adults. PMID- 1899132 TI - Tea tannin components modify the induction of sister-chromatid exchanges and chromosome aberrations in mutagen-treated cultured mammalian cells and mice. AB - The modifying effects of tannin components extracted from green tea and black tea on mutagen-induced SCEs and chromosome aberrations were studied. These tannin components did not affect spontaneous SCEs and chromosome aberrations in cultured Chinese hamster cells. The frequency of SCEs and chromosome aberrations induced by mitomycin C (MMC) or UV was enhanced by the posttreatment with tea tannin components. When cells were post-treated with tea tannin components in the presence of metabolic enzymes of rat liver (S9 mix), the modifying effects on the induction of SCEs and chromosome aberrations by mutagens were complicated. MMC- and UV-induced SCEs and chromosome aberrations were suppressed by the posttreatment with tea tannin components at low concentrations (less than or equal to 6.7 micrograms/ml) with S9 mix. At a high concentration of tea tannin components (20 micrograms/ml) with S9 mix, a co-mutagenic effect was observed. The modifying effects of tea tannin components were shown to occur in the G1 phase of the cell cycle. In cells from a patient with xeroderma pigmentosum (XP) and a normal human embryo, MMC-induced SCEs were suppressed by the posttreatment with tea tannin components in the presence of S9 mix, and enhanced in the absence of S9 mix. On the other hand, tea tannin components modified SCE frequencies in UV-irradiated normal human cells but not in UV-irradiated XP cells. Our results suggested that tea tannin components themselves inhibited DNA-excision repair and resulted in a co-mutagenic effect, while in the presence of S9 mix metabolites of tea tannin components promoted DNA-excision repair activity and resulted in an antimutagenic effect. MMC-induced chromosome aberrations in mouse bone marrow cells were suppressed by the pretreatment with green tea and black tea tannin mixture. PMID- 1899134 TI - Action stat! Complications of thrombolytic therapy. PMID- 1899135 TI - The significance of bleeding patterns in Norplant implant users. AB - The purpose of this study was to examine the bleeding patterns of 234 Norplant users during 5 years of use and to identify the bleeding patterns of users who conceived. During the first year of use, 26.6% of users had regular bleeding cycles, 66.3% had irregular cycles, and 7.1% were amenorrheic. By the fifth year of use, 62.5% of users had regular cycles, 37.5% had irregular cycles, and none had amenorrhea. Of the ten users who became pregnant, eight had regular menstrual cycles in the 6 months before the diagnosis of pregnancy, one had an irregular pattern, and one did not keep a bleeding record. None had amenorrhea. The 5-years cumulative pregnancy rate for patients with regular cycles was 17.4%; this was significantly higher (P less than .05) than the 5-year cumulative rates of 4.4% in users with irregular cycles and 0% in users with amenorrhea. This study indicates that during the first year of Norplant use, only 26.6% of users have regular cycles, but after the first year, 50-60% of users develop regular cycles. The bleeding patterns of women using Norplant improve after the first year of use, and those with regular cycles are at greatest risk for method failure. PMID- 1899136 TI - Protective effect of intrauterine release of levonorgestrel on pelvic infection: three years' comparative experience of levonorgestrel- and copper-releasing intrauterine devices. AB - A randomized, multicenter comparison of two intrauterine contraceptive devices (IUDs) was carried out. Nine hundred thirty-seven women were fitted with a copper releasing IUD, the Nova-T, and 1821 women with an IUD that releases 20 micrograms of levonorgestrel daily. After 36 months, the cumulative gross rates of amenorrhea and hormonal side effects were significantly higher in the levonorgestrel-IUD users. The cumulative 36-month gross pregnancy rate was 3.7 for the Nova-T and 0.3 for the levonorgestrel IUD (P less than .001), demonstrating the levonorgestrel IUD's high contraceptive efficacy. For the first time, a protective effect of the levonorgestrel IUD against pelvic inflammatory disease as compared with the Nova-T was seen statistically. The cumulative 36 month gross rate of pelvic inflammatory disease was 2.0 in Nova-T- and 0.5 in levonorgestrel-IUD users (P less than .013). This significantly lowered incidence of pelvic inflammatory disease may help to solve one of the major concerns associated with intrauterine contraception. PMID- 1899137 TI - The long-term care survey responses. PMID- 1899138 TI - Ribosomal RNA introns in archaea and evidence for RNA conformational changes associated with splicing. AB - The single 23S rRNA gene of the archaeon Staphylothermus marinus exhibits two introns which, at the RNA level, are located in highly conserved regions of domains IV and V. The RNA introns, which are 56 and 54 nucleotides long, respectively, can form single hairpin structures. In vivo, RNA splicing occurs efficiently, whereas in vitro pre-rRNA transcripts containing each intron were cleaved efficiently when incubated with archaeal cell extracts but were poorly ligated. The introns are cleaved by a mechanism which differs from the mechanisms of eukaryotic rRNA introns but resembles those of the rRNA intron of Desulfurococcus mobilis and the archaeal tRNA introns. The cleavage enzyme recognizes and cuts a putative bulge-helix-bulge structure that can form at the archaeal exon-intron junctions. Using a phylogenetic sequence comparison approach, we define the parts of this structural feature that are essential for cleavage. We also provide evidence for conformational changes occurring in the S. marinus 23S RNA, after cleavage, at both exon-exon junctions, which may account for the low yields of ligation observed in vitro. PMID- 1899139 TI - Amplification of major histocompatibility complex class II gene diversity by intraexonic recombination. AB - The roles of mutational and recombinational processes in the diversification of the exon encoding the antigen binding site in the murine major histocompatibility complex class II gene Ab were assessed by phylogenetic analysis of allelic nucleotide sequences. A total of 46 alleles of Ab exon 2 from 12 Mus species or subspecies and 2 Rattus species were sequenced after amplification by the polymerase chain reaction. Reliable allelic genealogies could not be determined by phylogenetic analyses, due to extensive homoplasy in the data set. This homoplasy results from the shuffling of polymorphisms between alleles by recombinational processes, indicating that polymorphisms in the antigen binding site encoded by Ab are generated by a combination of two processes. First, the accumulation of point mutations has produced highly divergent polymorphic sequence motifs in five regions of Ab exon 2, each encoding a portion of the binding site. Some of these motifs have persisted as polymorphisms in rodents since before the divergence of mouse and rat (greater than 10 million years ago). The second process mediating Ab diversification involves the shuffling of these polymorphic sequence motifs into numerous allelic combinations by repeated intraexonic recombination. Site-specific hyperrecombinational mechanisms are not involved in this process within the exon. We postulate that these mechanisms continuously generate new Ab alleles with highly divergent binding sites from which alleles with advantageous antigen-binding properties are selectively maintained by some form of balancing selection. PMID- 1899140 TI - Role of a carboxyl-terminal helix in the assembly, interchain interactions, and stability of aspartate transcarbamoylase. AB - The six individual catalytic polypeptide chains within the two catalytic trimers of Escherichia coli aspartate transcarbamoylase (ATCase; EC 2.1.3.2) are folded into two discrete structural domains interconnected in part by helix 12, which comprises residues 285-305 and is located near the carboxyl terminus of the chain. The essential role of this helix in folding of the chains and their assembly into ATCase was demonstrated by introducing a stop codon at the position corresponding to amino acid 284, 291, or 299. Cells containing these mutations are pyrimidine auxotrophs lacking ATCase-like protein in cell extracts. In contrast, stable active enzyme is formed from chains truncated at position 306 or 307, showing that all 310 amino acids are not required for assembly. Replacements of Gln-288, Asn-291, Arg-296, and Ala-298 were introduced to assess the effect of alterations within helix 12 on protein stability. Stability of the trimers was measured both by differential scanning microcalorimetry and by the rate of exchange of chains at 4 degrees C when mutant trimers were incubated with succinylated wild-type trimers. Melting temperatures of the mutant trimers spanned a range of more than 20 degrees C, with a few higher and others lower than that of wild-type trimers. Large changes in interchain interaction energies were observed for the trimers, but there was no direct correlation between the ease of dissociation of the trimers and their thermal stability. Calorimetry on the mutant holoenzymes revealed alterations in the interactions between trimers and regulatory subunits within the intact enzymes. The striking changes in stability of both trimers and holoenzymes demonstrated that effects of relatively localized amino acid replacements in helix 12 are manifested by indirect global alterations propagated throughout the structure. PMID- 1899141 TI - Envelope glycoproteins from biologically diverse isolates of immunodeficiency viruses have widely different affinities for CD4. AB - The envelope glycoprotein gp120 of primate immunodeficiency viruses initiates viral attachment to CD4+ cells by binding to the CD4 antigen on host cell surfaces. However, among different CD4+ cell types, different viruses display distinct host cell ranges and cytopathicities. Determinants for both of these biological properties have been mapped to the env gene. We have quantitatively compared the CD4 binding affinities of gp120 proteins from viruses exhibiting different host cell tropisms and cytopathicities. The viral proteins were produced by using a Drosophila cell expression system and were purified to greater than 90% homogeneity. Drosophila-produced gp120 from T-cell tropic human immunodeficiency virus type 1 (HIV-1) BH10 exhibits binding to soluble recombinant CD4 (sCD4) and syncytia inhibition potency identical to that of pure authentic viral gp120. Relative to the affinity of HIV-1 BH10 gp120 for sCD4, that of dual tropic HIV-1 Ba-L is 6-fold lower, that of restricted T-cell tropic simian immunodeficiency virus mac is 70-fold lower, and that of noncytopathic HIV 2 ST is greater than 280-fold lower. Thus, viruses that utilize CD4 for infection do so by using a remarkably wide range of envelope affinities. These differences in affinity may play a role in determining cell tropism and cytopathicity. PMID- 1899144 TI - Nurse round table discussion. Infections in the OR: are you at risk? PMID- 1899142 TI - The role of CD4+ and CD8+ T cells in the destruction of islet grafts by spontaneously diabetic mice. AB - Spontaneous development of diabetes in the nonobese diabetic (NOD) mouse is mediated by an immunological process. In disease-transfer experiments, the activation of diabetes has been reported to require participation of both CD4+ and CD8+ T-cell subsets. These findings seem to indicate that the CD4+ cells are the helper cells for the activation of cytotoxic CD8+ cells that directly destroy islet beta cells in type I diabetes. In this report we challenge this interpretation because of two observations: (i) Destruction of syngeneic islet grafts by spontaneously diabetic NOD mice (disease recurrence) is CD4+ and not CD8+ T-cell dependent. (ii) Disease recurrence in islet tissue grafted to diabetic NOD mice is not restricted by islet major histocompatibility complex antigens. From these observations we propose that islet destruction depends on CD4+ effector T cells that are restricted by major histocompatibility complex antigens expressed on NOD antigen-presenting cells. Both of these findings argue against the CD8+ T cell as a mediator of direct islet damage. We postulate that islet damage in the NOD mouse results from a CD4+ T-cell-dependent inflammatory response. PMID- 1899143 TI - Cell-autonomous role of Notch, an epidermal growth factor homologue, in sensory organ differentiation in Drosophila. AB - The gene Notch (N) codes for a transmembrane protein with an extracellular domain that has homologies to epidermal growth factors and an intracellular domain that could be involved in signal transduction. N null alleles cause the transformation of most epidermal cells into neuroblasts in central and peripheral nervous systems. Alleles of the same gene, called Abruptex (Ax), that map to the extracellular domain of N protein cause the absence of adult sensory organs. Both types of alleles show cell autonomy in mosaic analysis carried out in the last stages of the formation of adult sensory organs. The phenotypes are different: cells lacking N gene products differentiate as sensory organ mother cells early and as its neural sublineage later, whereas in the homozygous Ax condition epidermal cells do not enter the sensory organ mother cell pathway. The results indicate that N gene products act internally in the cell, probably as receptors of intercellular signals both in sensory organ mother cell singularization and in fate specification of its daughter cells. Ax mutations behave as an excess of N+ function in this signal transduction process. N proteins modified by these mutations act as constitutively activated. PMID- 1899145 TI - Sequential immunosuppression: three years' experience in 240 cadaveric renal transplants. PMID- 1899146 TI - The effect of induction ALG (MALG) on the outcome of steroid-resistant rejection treated with OKT3 in renal transplant patients. PMID- 1899147 TI - The use of OKT3 in the treatment of acute vascular rejection. PMID- 1899148 TI - Beneficial effects of prophylactic OKT3 in cadaver kidney transplantation: comparison with cyclosporin A in a single-center prospective randomized study. PMID- 1899149 TI - MALG vs OKT3 following renal transplantation: a randomized prospective trial. PMID- 1899150 TI - A prospective randomized comparison of prophylactic ALG and OKT3 in cadaver kidney allograft recipients. PMID- 1899151 TI - Cardiac allograft cellular rejection during OKT3 prophylaxis in the absence of sensitization. PMID- 1899153 TI - The changing pattern of posttransplant malignancies. PMID- 1899152 TI - Treatment of acute rejection with anti-T-cell antigen receptor complex alpha beta (T10B9.1A-31) or anti-CD3 (OKT3) monoclonal antibody: results of a prospective randomized double-blind trial. PMID- 1899154 TI - Antimurine antibody to OKT3 in cardiac transplantation: implications for prophylaxis and retreatment of rejection. PMID- 1899155 TI - Endothelial cell haemostatic function after heart transplantation. PMID- 1899156 TI - Effects of intracoronary acetylcholine infusion early versus late after heart transplant. PMID- 1899158 TI - Haemostatic changes after heart transplantation and their relationship to accelerated coronary sclerosis. PMID- 1899157 TI - Cystic fibrosis patients who have undergone heart-lung transplantation benefit from maxillary sinus antrostomy and repeated sinus lavage. PMID- 1899159 TI - Transfusion effect still present with quadruple immunosuppression in recipients of renal transplants. PMID- 1899161 TI - Should cadaveric donors with positive serology for Chagas' disease be excluded from kidney transplantation? PMID- 1899160 TI - HLA-DR1, -DR5, and -DR8 antigen disparities are associated with acute steroid resistant rejection and poor kidney graft survival. PMID- 1899162 TI - Retention of graft-versus-leukemia using selective depletion of CD8-positive T lymphocytes for prevention of graft-versus-host disease following bone marrow transplantation for chronic myelogenous leukemia. PMID- 1899163 TI - Undecalcified preparation of bone tissue: report of technical experience and development of new methods. AB - For reliable quantitative and qualitative analysis of bone specimens undecalcified preparation is essential. The "conventional" technique for this purpose is embedding in methylmethacrylate. Larger bone specimens, highly sclerotic specimens, cortical bone or bone implants consisting of metals or ceramics require modifications of this technique or completely new methods. We report our experience with the undecalcified preparation of 47,700 bone specimens. New techniques such as the cutting of large area sections up to a size of 5 x 6 cm and grinding procedures for completely artefact-free preparation which are applied in special cases are also described. A new technique of combined two- and three-dimensional analysis of bone specimens is presented. In our experience these methods are fundamental for morphological investigation of bone. PMID- 1899164 TI - The ultrastructural effects of global ischaemia on Purkinje fibres compared with working myocardium: a qualitative and morphometric investigation on the canine heart. AB - During open heart surgery, reperfusion-induced arrhythmias arising after short periods of ischaemia may originate from subendocardial Purkinje fibres. We investigated the ultrastructure of these fibres during 30 min of global ischaemia at 25 degrees C. The effects both with myocardial protection (HTK cardioplegia) and without it (pure ischaemia) were compared qualitatively and morphometrically. After 30 min pure ischaemia overcontraction of sarcomeres, hypercontraction and contraction bands, together with considerable changes in organelles, predominate over cellular oedema. In Purkinje fibres, both cellular and mitochondrial swelling were significantly increased within this 30-min time period from the onset of pure ischaemia. In contrast, following HTK cardioplegia and 30 min ischaemia, cellular and mitochondrial swelling remain moderate and over contractions are almost entirely lacking. This means that despite remarkable differences between pure ischaemia and HTK cardioplegia in the degree of protection attained it is clear that, compared with the working myocardium, subendocardial Purkinje fibres do not display a higher resistance to early global ischaemia. Further investigations of this sensitivity of Purkinje fibres to global ischaemia and certain drugs may bring about new insights into myocardial protection and pharmacotherapy of arrhythmias. PMID- 1899165 TI - Immunohistochemical characterization of HLA-DR-antigen positive dendritic cells in phaeochromocytomas and paragangliomas as a prognostic marker. AB - Twelve cases of phaeochromocytoma (PCC) and four cases of paraganglioma (PGG) were studied by immunohistochemistry and immunoelectron microscopy in order to demonstrate HLA-DR (Ia)-antigen-positive dendritic cells (IaDCs). Dense infiltration of IaDCs was detected in the majority of PCCs revealing high urinary or serum catecholamine levels, but in aggressively growing PCCs, a familial PCC and all PGGs, few IaDCs were demonstrated. Interestingly, these IaDCs were negative for S-100 protein. Although S-100-protein-positive sustentacular-like cells (SCs), morphologically similar to IaDCs, were also present, these were clearly distinguished from IaDCs by our double immunostaining method. Ultrastructurally, IaDCs had smooth or slightly indented nuclei and contained a moderate amount of endoplasmic reticulum, small mitochondria and vacuoles, extending elongated cytoplasmic processes. These results suggest that determination of the quantity of IaDCs is a highly effective method of assessing the character of PCCs, in particular, their prognosis. PMID- 1899166 TI - Cell-mediated cytotoxicity in acute rat cardiac allograft rejection: an immunological and ultrastructural study. AB - To clarify the immune mechanism of cytotoxicity in acute cardiac allograft rejection, we observed interactions between cardiocytes and mononuclear cells using immunohistochemistry and light and electron microscopy. All allografted WKA rat hearts transplanted to F344 recipients stopped beating by the 7th day after the transplantation. The population of helper/inducer T cells (Th) and IL2R+ cells was large for the first 3 days, whereas that of cytotoxic/suppressor T cells (Tc-s) and macrophages increased from the 4th day. The Th/Tc-s ratios were more than 2.0 until the 3rd day, then decreased to less than 1.0. In circulating T lymphocytes; the Th/Tc-s ratios were under 1.0 on the 1st, 6th and 7th days. Electron microscopically IL2R+ cells, Tc-s and macrophages were often seen in close contact with the plasma membrane of the cardiocytes. The majority of IL2R+ cells are NK cells, Tc-s and Th. Of these, the population of Tc-s was small until the 3rd day. Thus, NK cells play a pivotal role in the early stage of the rejection, and Tc-s and macrophages then aggravate cell-mediated cardiocyte injury. PMID- 1899167 TI - Ultrastructure of matriceal changes in chronic phase of Masugi nephritis by quick freezing and deep-etching method. AB - The three-dimensional ultrastructure of glomerular sclerosis in the chronic phase of Masugi nephritis was investigated using a quick-freezing and deep-etching method. Newly formed mesangial matrix, which was increased in the axial portions, was composed of fine fibrillar networks similar to those in the lamina densa of the basement membrane. These fibrils were 10-20 nm in diameter and directly attached to the cell membranes of mesangial cells, endothelial cells and podocytes by connecting fibrils. Moreover, thicker fibrils with diameters of 20 30 nm were present in the networks and were connected with cross-bridges. A newly formed matrix of fine fibrillar networks was also seen in the areas of mesangial interposition in the glomerular capillary wall. The border between the matrix and lamina densa was unclear. The fibrils organizing the networks of lamina densa of the glomerular loop were thickened, with some decoration. Connecting fibrils were disrupted in the areas of endothelial detachment. It is suggested that prolonged tissue injury with endothelial detachment might induce mesangial sclerosis composed of fine fibrillar networks. The increase in density of the networks seemingly interfere with the contractile function of mesangial cells, which is followed by alteration of mesangial flow. PMID- 1899168 TI - Three-dimensional studies of the cytoskeleton of cultured hepatocytes: a quick freezing and deep-etching study. AB - The ultrastructure of the cytoskeleton of cultured mouse hepatocytes was studied by a quick-freezing and deep-etching method. Isolated mouse hepatocytes were cultured on collagen gels for 48 h, fixed in paraformaldehyde and centrifuged to prepare cell pellets. The hepatocytes were split open to remove cytoplasmic soluble proteins for replica preparations. Some specimens were decorated with anti-actin antibody or S1 myosin fragments to identify actin filaments. They were quickly frozen in isopentane-propane mixture, fractured in liquid nitrogen, deeply etched in a freeze-fracture machine and rotary shadowed by platinum and carbon. The basal cell membranes of hepatocytes were in contact with the collagen gels and the apical surface faced the culture medium. Networks of actin filaments were attached to the apical cell membranes, but intermediate filaments were localized along the basal layer. Some intermediate filaments were associated with cell organelles, such as the endoplasmic reticulum. The Golgi apparatus was less associated with the cytoskeleton and showed synthesized materials in the cisternae. Cytoskeletal organization in cultured hepatocytes was revealed three dimensionally, indicating that the interaction of cell membranes with collagen gels is important for the organization of the cytoskeleton. PMID- 1899169 TI - Acute ascending necrotizing myelitis in Okinawa caused by herpes simplex virus type 2. AB - A case of rapidly progressing ascending myelitis was necropsied. Necrosis was present throughout the whole length of the spinal cord and involved both the grey and white matter randomly. The perivascular lymphocytic infiltration in the spinal cord in the present case was more pronounced than that in the previously reported two cases of necrotizing myelopathy associated with malignancy. Using immunoperoxidase staining the presence of herpes simplex virus type 2 (HSV 2) antigen was demonstrated. Electron microscopic examinations revealed large numbers of HSV particles in the spinal cord. HSV 2 may be a common aetiological agent of necrotizing myelopathy and myelitis in Okinawa, an HSV 2 endemic area. In the present case, the necrosis was mainly found in the spinal cord but was also observed, to a very limited extent, in the brain. PMID- 1899170 TI - The 5' noncoding region sequence of the Choristoneura biennis entomopoxvirus spheroidin gene functions as an efficient late promoter in the mammalian vaccinia expression system. AB - About 100 nucleotides of DNA sequence at the 5' noncoding region of the Choristoneura biennis entomopoxvirus spheroidin gene was chemically synthesized and inserted into a vaccinia expression vector, interrupting the vaccinia thymidine kinase gene. When the bacterial beta-galactosidase gene was introduced downstream of this sequence and a recombinant vaccinia virus containing these inserts was obtained by homologous recombination, beta-galactosidase was shown to be expressed at a high level late in the vaccinia infection cycle. The level of beta-galactosidase expression was four- to fivefold higher with this spheroidin vaccinia recombinant virus than with a similar recombinant in which the beta galactosidase gene was under the control of the vaccinia 7.5-kDa promoter. Primer extension and S1 mapping of the 5' terminus of the beta-galactosidase transcript located the transcription initiation site within the spheroidin DNA sequence, confirming the promoter nature of this DNA sequence in the vaccinia system. Dot blot analysis indicated that the difference in beta-galactosidase expression with these two recombinant viruses can be attributed to the difference in their transcript levels. We also demonstrated that full promoter activity encoded in the spheroidin 5' noncoding sequence was contained within a 38-nucleotide DNA fragment. PMID- 1899171 TI - Parenteral drug products containing aluminum as an ingredient or a contaminant: response to FDA notice of intent. ASCN/ASPEN Working Group on Standards for Aluminum Content of Parenteral Nutrition Solutions. PMID- 1899172 TI - Interrelationship between protein-energy malnutrition and essential fatty acid deficiency in nursing infants. AB - The influence of severe protein-calorie malnutrition on essential fatty acid (EFA) status was evaluated in nursing infants aged 2-5 mo. A control group of the same age and with normal weight-for-height was also selected for this study. The fatty acid pattern of total phospholipids from plasma and red blood cells (RBCs) was determined and then used as a biochemical variable for evaluating EFA status. A sharp fall in the relative percentage of n-6 (omega-6) fatty acids concomitant with an increase in the n-9 fatty acids in plasma and RBC phospholipids was observed. These results are consistent with the picture of EFA deficiency and showed that the deficiency state is well correlated with the severity of malnutrition. Calculation of the product-precursor ratio of polyunsaturated fatty acids derived from linoleic acid (18:2n-6) in RBC phospholipids provides evidence for an impairment in the elongation-desaturation pathway promoted by the protein calorie malnutrition. PMID- 1899173 TI - Dietary saturated fatty acids (12:0, 14:0, 16:0) differ in their impact on plasma cholesterol and lipoproteins in nonhuman primates. AB - Three species of monkey (rhesus, cebus, and squirrel) were rotated through five purified diets containing 31% energy as various fat blends (P:S between 0.1 and 1.0) for 12-wk periods to compare the impact of specific dietary fatty acids on plasma lipids and lipoproteins. As 12:0 + 14:0 was replaced by 16:0, a significant decrease occurred in total and LDL cholesterol, whereas slight increases in total cholesterol and the LDL-HDL ratio occurred when 16:0 replaced 18:2. Hegsted and Keys regression equations provided a good fit for the observed data, but the predicted total cholesterol response was perfect (r = 0.995) for both equations when 16:0 was considered neutral. Thus, under these conditions 16:0 was less cholesterolemic than 12:0 + 14:0 and only slightly cholesterolemic compared with 18:2. PMID- 1899174 TI - Altered maturation of small intestinal function in the absence of intraluminal nutrients: rapid normalization with refeeding. AB - The absence of intraluminal nutrients during weaning in rats was shown to result in altered intestinal growth and maturation. In this study intestinal length, mucosal weight, DNA, protein, and total disaccharidase activities were significantly lower in animals sustained by intravenous nutrients over the normal weaning age than were normally weaned controls but were greater than preweaning values. Absorptive capacity for sucrose (assessed by hydrogen-gas production) was diminished, directly linking incomplete maturation of sucrase to diminished intestinal function. To determine whether these alterations were permanent, rats previously deprived of intraluminal nutrients over the weaning period were refed. Eight days after refeeding, all variables except total lactase had attained values found in normally weaned age-matched controls, including absorptive capacity for sucrose. Although intestinal growth and maturation is abnormal in the absence of intraluminal nutrients during weaning, the abnormalities are not permanent and are rapidly corrected upon refeeding. PMID- 1899175 TI - Canthaxanthin toxicity. PMID- 1899176 TI - Gene cluster rpoBC1C2 in cyanobacteria does not constitute an operon. AB - The core enzyme of the cyanobacterial DNA-dependent RNA polymerase contains a unique component, gamma, which is absent from the corresponding enzymes of other eubacteria. In the heterocystous cyanobacterium Nostoc commune the gene encoding gamma, rpoC1, is immediately adjacent to, and downstream of, rpoB. The rpoC1 gene, and a 3' adjacent gene, rpoC2, correspond to the single rpoC gene found in Escherichia coli with respect to those domains conserved within their translational products. Northern analysis and primer extension assay show that in N. commune, rpoC1 and rpoC2 are transcribed separately from rpoB. The promoter of rpoC1C2 can direct the expression of a promotorless lacZ gene in E. coli. As a consequence, cyanobacterial rpo gene expression is distinct from the mode of cotranscription described for the equivalent sequences found in other eubacteria, archaebacteria, and plant chloroplasts. Also in this paper, a simple protocol for RNA isolation, which should be applicable for RNA isolation from plant cells, is presented. PMID- 1899177 TI - The effect of divalent cations on the conformation and function of human plasminogen. AB - The activation of native human plasminogen (Glu1-Pg) by tissue plasminogen activator, urinary plasminogen activator (u-PA), and streptokinase is inhibited by the divalent cations Ca2+, Mg2+, and Mn2+. This inhibition is accompanied by a conformational change in the molecule as evidenced by a decrease in Stokes' radius and intrinsic fluorescence. Kinetic analysis indicates that Mn2+ acts as an uncompetitive inhibitor of u-PA-catalyzed Glu1-Pg activation. In contrast to the inhibitory effects of divalent cations on Glu1-Pg, Ca2+ and Mg2+ stimulate the activation of proteolytically modified Lys77-Pg. These observations provide further evidence that Glu1-Pg and Lys77-Pg exhibit differential responses to ligands in the microenvironment. PMID- 1899178 TI - The dysfunctional LDL receptor in a monensin-resistant mutant of Chinese hamster ovary cells lacks selected O-linked oligosaccharides. AB - The Chinese hamster ovary (CHO) cell line Monr31, which is resistant to the cytotoxic ionophore monensin, produces a receptor for the low density lipoprotein (LDL) that has a lowered binding affinity for LDL and is approximately 5 kDa smaller in size than the receptor from parental CHO cells. It has been proposed that the reduced size and affinity for LDL are associated with a reduced level of O-glycosylation of Ser/Thr residues in the receptor. To examine this possibility in more detail, both parental CHO and Monr31 cells were metabolically radiolabeled with [3H]glucosamine, and the labeled LDL receptors were purified by immunoprecipitation and identified by SDS-PAGE-fluorography. The Ser/Thr-linked oligosaccharides in the receptors from both parental CHO and Monr31 cells are mono- and desialylated species having the common core structure Gal beta 1 3GalNAc. The receptor from Monr31 cells, however, contains about one-third fewer Ser/Thr-linked oligosaccharides than the receptor from parental CHO cells. Analysis of the glycopeptides derived from the Monr31 cell LDL receptors indicates that they contain Ser/Thr-linked oligosaccharides only in the clustered domain and are missing Ser/Thr-linked oligosaccharides in the unclustered regions of the protein. Additionally, analysis of a human LDL receptor lacking the domain for attachment of the clustered Ser/Thr-linked oligosaccharides and expressed in both parental CHO and Monr31 cells indicated that the truncated human receptor from Monr31 cells is devoid of Ser/Thr-linked oligosaccharides. In contrast, the truncated human receptor produced by parental CHO cells contains Ser/Thr-linked oligosaccharides contributing approximately 5 kDa to its apparent size. Collectively, these results demonstrate that the LDL receptor produced by the Monr31 cells contains Ser/Thr-linked oligosaccharides in the clustered domain but is missing Ser/Thr-linked oligosaccharides in the unclustered, NH2-terminal domains of the receptor. PMID- 1899179 TI - Identification of an abundant S-thiolated rat liver protein as carbonic anhydrase III; characterization of S-thiolation and dethiolation reactions. AB - An S-thiolated 30-kDa protein has been purified from rat liver by two steps of ion-exchange chromatography. This monomeric protein has two "reactive" sulfhydryls that can be S-thiolated by glutathione (form a mixed disulfide with glutathione) in intact liver. The protein has been identified as carbonic anhydrase III by sequence analysis of tryptic peptides from the pure protein. The two "reactive" sulfhydryls on this protein can produce three different S thiolated forms of the protein that can be separated by isoelectric focusing. Using this technique it was possible to study the S-thiolation and dethiolation reactions of the pure protein. The reduced form of this protein was S-thiolated both by thiol-disulfide exchange with glutathione disulfide and by oxyradical initiated S-thiolation with reduced glutathione. The S-thiolation rate of this 30 kDa protein was somewhat slower than that of glycogen phosphorylase b by both S thiolation mechanisms. The S-thiolated form of this protein was poorly dethiolated (i.e., reduced) by glutathione, cysteine, cysteamine, or coenzyme A alone. Enzymatic catalysis by two different enzymes (glutaredoxin and thioredoxin like) greatly enhanced the dethiolation rate. These experiments suggest that carbonic anhydrase III is a major participant in the liver response to oxidative stress, and that the protein may be S-thiolated by two different non-enzymatic mechanisms and dethiolated by enzymatic reactions in intact cells. Thus, the S thiolation/dethiolation of carbonic anhydrase III resembles glycogen phosphorylase and not creatine kinase. PMID- 1899180 TI - Myotoxin II from Bothrops asper (Terciopelo) venom is a lysine-49 phospholipase A2. AB - A basic, dimeric myotoxic protein, myotoxin II, purified from Bothrops asper venom has a similar molecular weight and is immunologically cross-reactive with antibodies raised to previously isolated B. asper phospholipases A2, except that it shows only 0.1% of the phospholipase activity against L-alpha phosphatidylcholine in the presence of Triton X-100. Its 121 amino acid sequence, determined by automated Edman degradation, clearly identifies it as a Lys-49 phospholipase A2. Key amino acid differences between myotoxin II and phospholipase active proteins in the Ca2(+)-binding loop region, include Lys for Asp-49, Asn for Tyr-28, and Leu for Gly-32. The latter substitution has not previously been seen in Lys-49 proteins. Other substitutions near the amino terminus (Leu for Phe-5 and Gln for several different amino acids at position 11) may prove useful for identifying other Lys-49 proteins in viperid and crotalid venoms. Myotoxin II shows greater sequence identity with other Lys-49 proteins from different snake venoms (Agkistrodon piscivorus piscivorus, Bothrops atrox, and Trimeresurus flavoviridis) than with another phospholipase A2 active Asp-49 molecule isolated from the same B. asper venom. This work demonstrates that phospholipase activity per se, is not required in phospholipase molecules for either myotoxicity or edema inducing activities. PMID- 1899181 TI - 5-Enolpyruvylshikimate-3-phosphate synthase from Escherichia coli--the substrate analogue bromopyruvate inactivates the enzyme by modifying Cys-408 and Lys-411. AB - In order to identify the essential reactive amino acid residues of 5 enolpyruvylshikimate-3-phosphate synthase, the reaction of the enzyme with its substrate analogue bromopyruvate was investigated. Incubation of the enzyme with bromopyruvate resulted in a time-dependent loss of enzyme activity. The inactivation followed pseudo-first-order and saturation kinetics with a Kinact of 28 microM and a maximum rate constant of 0.31 min-1. The inactivation was prevented by preincubation of the enzyme with the substrates shikimate 3 phosphate, 5-enolpyruvylshikimate 3-phosphate or by the combination of shikimate 3-phosphate plus glyphosate (N-phosphonomethylglycine), an inhibitor of the enzyme. Addition of sodium [3H]borohydride to the reaction mixture had no effect on the rate of inactivation but resulted in the incorporation of 3H label to the modified enzyme. Upon 90% inactivation, approximately 1 mol of bromo[14C]pyruvate was incorporated per mole of enzyme modified in the absence or presence of sodium borohydride. When the enzyme was incubated with bromopyruvate in the presence of sodium [3H]borohydride, approximately 1 mol of 3H label was found to be associated per mole of the modified enzyme. Tryptic digestion of these labeled proteins followed by reverse phase chromatographic separation resulted in the isolation of three radioactive peptides. Analyses of these three peptides indicated that bromopyruvate inactivated the enzyme by modifying Cys-408 and Lys 411, which are conserved in all enzyme sequences studied to date. PMID- 1899182 TI - Could glucose-insulin-potassium be considered only a step of a complete nutritional program for complicated cardiac patients? PMID- 1899183 TI - Endocrine, cardiovascular, and behavioral effects of intravenous protirelin in patients with panic disorder. AB - The effects of protirelin administration on the anterior pituitary release of thyrotropin and prolactin were examined in 26 patients with panic disorder and 22 healthy volunteers. There were no differences observed in hormonal responses to protirelin between patients and controls. However, higher Beck Depression Inventory scores were associated with smaller baseline-corrected maximal changes in thyrotropin responses. Cardiovascular responses to protirelin did not differ between a subgroup of 15 patients with panic disorder and 15 age- and sex-matched healthy controls. Although protirelin produced robust increases in heart rate and blood pressure, only one patient with panic disorder experienced a panic attack during the infusion. The hormonal findings suggest that the presence of depressive symptoms may have a significant impact on various indexes of neuroendocrine responsivity and should be taken into consideration when looking at biologic measures in patients with panic disorder. The cardiovascular and behavioral findings do not support the hypothesis that all panic-producing stimuli are nonspecific and suggest that the induction of physical stimuli may be insufficient to produce panic attacks even in susceptible individuals. PMID- 1899184 TI - Tau in Alzheimer neurofibrillary tangles. N- and C-terminal regions are differentially associated with paired helical filaments and the location of a putative abnormal phosphorylation site. AB - To investigate the extent to which whole tau proteins, structurally abnormal tau and fragments of tau are incorporated into neurofibrillary tangles in Alzheimer's disease, an immunocytochemical mapping study using a panel of antibodies to several synthetic human tau peptides has been performed. Neurofibrillary tangles were immunolabelled in situ, and paired helical filaments (PHF), the principal structural component of tangles, were immunolabelled after isolation and Pronase treatment. N-Terminal and C-terminal domains of tau were found to be present in tangles in situ. SDS-treated PHF were found to contain most of the C-terminal half of tau and were also labelled by antibodies to ubiquitin. Only some of these PHF were labelled by antisera to tau sequences towards the N-terminus, and this enabled the identification of a region of tau in which proteolytic cleavage may occur. The ultrastructural appearance of the immunolabelling suggested that both the N- and C-terminal domains of tau extend outwards from the axis of PHF. After Pronase treatment. PHF were strongly labelled only by an antiserum to PHF and by the antiserum to the most C-terminal tau synthetic peptide. The latter antiserum also strongly labelled extracellular tangles in situ, whereas these extracellular tangles were poorly labelled by the antisera to the other synthetic peptides. One anti-(tau peptide) serum labelled a population of neurofibrillary tangles in situ only after alkaline phosphatase pretreatment of tissue sections. Our results show that, although peptides along the length of the tau molecule are associated with neurofibrillary tangles in situ, only the C-terminal one-third of the molecule is tightly associated with PHF, since this region of tau is resistant to SDS treatment of PHF. We also report the existence in PHF in situ of a masked tau epitope which is partially unmasked by dephosphorylation. These results are indicative of post-translational changes in tangle-associated tau in degenerating neurons in Alzheimer's disease. PMID- 1899185 TI - Specificity of two genetically related cell-envelope proteinases of Lactococcus lactis subsp. cremoris towards alpha s1-casein-(1-23)-fragment. AB - The specificity of two genetically related cell-envelope serine proteinases (PI type and PIII-type) of Lactococcus lactis subsp. cremoris towards the alpha s1 casein-(1-23)-fragment, an important intermediate product of primary chymosin directed proteolysis in cheese, has been established. Both enzymes showed, at pH 6.5 and under relatively low-ionic-strength conditions, a characteristic, mutually different, cleavage pattern that seems, in the first instance, to be determined by the charge N-terminal to the cleaved bond. With Pi, three cleavage sites were found in the N-terminal positively charged part of the peptide and, with PIII, three sites were found in the C-terminal negatively charged part. Comparison of the specific cleavage sites in this peptide and those in beta casein revealed similarities with respect to the different residues which can occur N-terminally to the cleaved bond. The properties of these substrate residues match with the structural and various interactive features of the respective binding regions of the enzymes predicted on the basis of a close sequence similarity of the lactococcal proteinases with the subtilisin family. A hydrophobic interaction and/or hydrogen-bridge formation seems to govern the binding of the first amino acid residue N-terminal to the scissile bond. The more distantly N-terminally positioned sequence of residues apparently is attracted electrostatically by a negative charge in the binding region of PI and by a positive charge in that of PIII, provided that the opposite charge is is present at the appropriate position in this sequence. Hence a specific electrostatic binding may occur; additionally, hydrophobic interaction and/or hydrogen-bond formation is important. PMID- 1899186 TI - Sequence of the beta-subunit of the phosphatidylinositol-specific phospholipase C directed GTP-binding protein from squid (Loligo forbesi) photoreceptors. AB - The beta-subunit (G-beta) of the squid (Loligo forbesi) visual GTP-binding protein (G-protein), thought to be associated with a phosphatidylinositol specific phospholipase C, has been identified and the sequence of the protein determined from its cDNA. The predicted polypeptide has a very marked sequence similarity with its mammalian counterparts (80-90% identity). Squid G-beta also has somewhat lower similarity to the yeast protein STE4 (approx. 40% identity). The role of G-beta in signal transduction is discussed in the light of its pronounced structural conservation. PMID- 1899188 TI - Inhibition of ras-induced germinal vesicle breakdown in Xenopus oocytes by rap 1B. AB - A cDNA clone (Krev-1) has recently been identified that possesses the ability to reverse the transformed phenotype when introduced into a K-ras-transformed NIH/3T3 cell line. The Krev-1 protein, also known as rap-1A, was found to share 50% homology with the ras proteins. The rap-1A protein has also been shown to block the interaction of ras with its GTPase activating protein in vitro, leading to speculation regarding its role in vivo. A closely related protein, rap-1B, has also been identified in platelets, human erythroleukemia cells, neutrophils, and aortic smooth muscle cells. Unlike rap-1A, rap-1B has been shown to be phosphorylated in platelets. Given the high degree of similarity between the amino acid sequences of rap-1A and rap-1B, we sought to investigate the effect of microinjected rap-1B on H-ras(Val12)-induced germinal vesicle breakdown in Xenopus laevis oocytes. In this assay system, equimolar concentrations of rap-1B were found to block germinal vesicle breakdown triggered by the oncogenic ras protein. However, in the presence of IGF-1, this inhibition was not observed. Moreover, rap-1B is readily phosphorylated in the oocytes. PMID- 1899187 TI - An unsulphated region of the rat chondrosarcoma chondroitin sulphate chain and its binding to monoclonal antibody 3B3. AB - The chondroitin sulphate chains of proteoglycans are not uniformly sulphated. Commonly, regions of under- and over-sulphation are found. It is probable that variability in chondroitin sulphation has physiological significance, although such structure-function relationships largely remain unexplored. Chondroitin sulphate from rat chondrosarcoma proteoglycan has been found to possess no oversulphated residues. It is primarily chondroitin 4-sulphate, although a significant proportion of unsulphated disaccharides (14%) are also present. It appears that some unsulphated disaccharides are concentrated only at the point of attachment to the linkage region (i.e. it is the major unsaturated disaccharide remaining attached to chondrosarcoma proteoglycan core produced by chondroitinase ABC digestion). This proteoglycan core binds monoclonal antibody (MAb) 3B3. Although 3B3 principally binds to 6-sulphated 'stubs' of proteoglycan cores [Couchman, Caterson, Christner & Baker (1984) Nature (London) 307, 650-652], given a high concentration of unsulphated 'stubs', it can alternatively bind to these residues. It is also evident that caution must be exercised in using MAb 3B3 to identify chondroitin 6-sulphated proteoglycans. PMID- 1899189 TI - Effect of lymphokine-activated killer cells on human retinoblastoma cells (Y-79) in vitro: enhancement of the activity by a polysaccharide preparation, krestin. AB - Peripheral blood mononuclear cells (PBMC) cultured in a medium containing interleukin 2 (IL 2) develop the ability to kill fresh tumor cells. This function has been termed lymphokine activated killing (LAK). Recently, cord LAK cell activity was demonstrated to be equally as cytotoxic against similar in vitro targets as adult (peripheral) LAK cells. We investigated the future therapeutic use of LAK adoptive immunotherapy by examining LAK in vitro cytotoxicity from both cord and peripheral blood mononuclear cells against pediatric malignant tumor cell lines Y-79 (retinoblastoma). Cord LAK cells show higher levels of cytotoxicity toward Y-79 targets than do adult LAK cells. Attempts to enhance the rIL 2-induced LAK activity by addition of rIFN-gamma or PSK (krestin) were successful. Furthermore, we found that PSK has a function to enhance rIL 2 induced IFN-gamma and TNF-alpha production. These findings suggest that combined administration of cord LAK cells and PSK may account for the improvement of advanced retinoblastoma in the neonatal period. PMID- 1899190 TI - Clathrin-coated vesicles from human placenta contain GTP-binding proteins. AB - Biochemical and morphological techniques were used to investigate the GTP-binding proteins of clathrin-coated vesicles. Binding of [3H]GTP to clathrin coats was demonstrated by electron microscopic autoradiography. Purified coated vesicles bound 5.2 pmol [35S]GTP gamma S/mg protein. Addition of GTP or GTP gamma S, but not ATP nor GMP, inhibited binding of [35S]GTP gamma S to intact coated vesicles and Triton X-100-extracted coats. A series of 23-24 kDa GTP-binding proteins with isoelectric points between pH 5-8 were detected in coated vesicles. We suggest that the low molecular weight ras-like GTP-binding protein(s) play a role in regulating vesicle-mediated protein transport or signal transduction within intracellular organelles. PMID- 1899191 TI - Endothelin-3 inhibits prolactin and stimulates LH, FSH and TSH secretion from pituitary cell culture. AB - The influence of endothelin-3 (ET-3) on anterior pituitary hormone secretion was investigated over a wide range of concentrations (from 10(-14) to 10(-6) M) and incubation times (from 4 to 48 hours). ET-3 elicited a concentration-dependent inhibition of prolactin (PRL) secretion and stimulated the release of luteinizing hormone (LH), follicle stimulating hormone (FSH) and thyroid stimulating hormone (TSH) from primary monolayer cultures of anterior pituitary cells derived from female rats. The responsiveness of different pituitary cells to ET-3 differs markedly in terms of onset and duration: the maximal inhibition of PRL secretion occurred after 12 hours and the stimulation of LH, FSH and TSH reached the maximum after 4, 48 and 48 hours of incubation, respectively. These data corroborate the concept that ET-3 has an important role as a neuroendocrine modulator. Moreover, the data presented suggest different intracellular mechanisms underlying ET-3 actions. PMID- 1899192 TI - Phosphorylase kinase: development of a continuous fluorometric assay for the determination of catalytic activity. AB - The preferential binding of 1-anilinonaphthalene-8-sulfonate by rabbit muscle phosphorylase a is the basis of a continuous fluorometric assay for phosphorylase kinase. The maximum rate of change in fluorescence (d delta F/dt) is dependent on both the concentration of phosphorylase kinase and on conditions, such as pH and calcium ion concentration, which affect the enzyme. Parallel measurements of the increases in fluorescence and of 32P incorporation demonstrate the existence of a distinct intermediate in the conversion of phosphorylase b to a. We have used the assay to monitor the increase in calcium-independent activity which accompanies the limited chymotryptic digestion of phosphorylase kinase. PMID- 1899193 TI - Cytosolic free Ca2+ in daunorubicin and vincristine resistant Ehrlich ascites tumor cells. Drug accumulation is independent of intracellular Ca2+ changes. AB - The possible role of intracellular calcium on daunorubicin (DNR) accumulation in wild-type (EHR2) and multi-drug resistant (MDR) Ehrlich ascites tumor cell subline was investigated. DNR accumulation was not enhanced either by increasing the concentration of cellular calcium with the calcium ionophore ionomycin nor by chelating the cytosolic free Ca2+ by the membrane permeable Ca2(+)-buffering agents BAPTA or MAPTAM. No effect was observed in the presence of extremely low extracellular calcium concentration that prevent transmembrane calcium influx or when the cells were calcium depleted using EGTA and ionomycin. Using the fluorescent Ca2+ indicator fura-2 it is further shown that both drug-resistant daunorubicin (EHR2/DNR+) and vincristine (EHR/VCR+) sublines had lower (50-80 nM) concentration of cytosolic free calcium ([Ca2+]i) compared to their corresponding wild-type parenteral tumors (140-180 nM). In calcium free medium, however, no significant difference was found, all cell lines having a [Ca2+]i of 60-80 nM. Furthermore, the total amount of Ca2+ released to the cytosol with 10 microM ionomycin and 5 mM EGTA was 3-4-fold higher in EHR2 than in EHR2/DNR+ or EHR2/VCR+. Mobilization of Ca2+ with 1 microM ionomycin was almost identical in the presence and absence of Ca2+ in the extracellular medium in EHR2 as well as in EHR2/DNR+ suggesting that the increase in [Ca2+]i is mainly due to discharge of Ca2+ from intracellular stores. Furthermore, the total cell calcium [Ca2+]t concentration was slightly higher in EHR2/DNR+ and EHR2/VCR+ cells compared to EHR2. Incubation of the cells with the Ca2(+)-channel blocker verapamil or the intracellular Ca2(+)-antagonist TMB-8 causes depression of the Ca2(+)-response in terms of rise in [Ca2+]i caused by ionomycin. Sorcin, a major calcium-binding protein (Mr 22 kDa), is shown to be overproduced in EHR2/DNR+ cells. The overproduction of this protein in resistant cells may be related to the difference in the intracellular calcium observed in this study. Thus, though handling of Ca2+ is different in wild-type and MDR cell lines, our data suggest that calcium is not involved directly in drug transport processes and the level of Ca2+ per se have no influence on drug accumulation. PMID- 1899194 TI - Interference of xanthate compounds with phorbol ester TPA-induced changes of phospholipid metabolism: inhibition of prostaglandin production. PMID- 1899196 TI - Gene replication in the presence of aphidicolin. AB - DNA replication in the nucleus of eukaryotic cells is restricted to the S phase of the cell cycle, and different genes are duplicated at specific times, according to a well-defined temporal order. We have investigated whether activation of initiation sites, in proximity to genes that are replicated in different portions of the S phase, could be detected when synchronized 10T1/2 cells were maintained in aphidicolin (APC), an inhibitor of DNA polymerases alpha and delta. Cells released from confluence arrest into medium containing 2 micrograms/mL APC progressed into the S phase, and nascent DNA accumulated during incubations of 24 and 32 h. Exposure to APC for 40 or 48 h resulted in growth of the radiolabeled DNA into larger molecules. Replicating DNA was isolated in CsCl gradients and probed with 32P-labeled gene probes for early-replicating genes (e.g., Ha-ras, mos, and myc) and a late-replicating gene (VH Ig). DNA replicated during the 24-h incubation in APC was enriched in Ha-ras gene sequences. The VH Ig gene did not replicate in cells incubated for as long as 56 h with APC. The myc and the mos genes were detected after 32 and 40 h in APC, respectively. The myc gene is replicated in 10T1/2 cells after Ha-ras but before mos. Therefore, the order of activation of these genes was conserved in the presence of APC. The delay in replication of myc and mos correlated well with the slowing of DNA replication by APC. PMID- 1899195 TI - Subrenal capsule assay in selection of chemotherapy after operation for recurrent ovarian cancer. AB - Forty-six patients with recurrent ovarian cancer were reoperated, and cancer samples for the subrenal capsule assay (SRCA) were collected from 23 of them, whereas this test was not done in the remaining 23 control patients. The SRCA was evaluable in 22 cases (96%). Taken together, no significant difference appeared in the 3 years' survival figures between the groups: seven of 22 patients (32%) with the evaluable SRCA and six of 23 control patients (26%) were alive. However, a further analysis of the data revealed that the SRCA guided the selection of chemotherapy only in 15 patients, whereas tumour samples were resistant to all cytostatics tested in six cases and toxic side-effects limited the clinical application of the test results in the remaining one case. Four of the 11 patients (36%) whose further chemotherapy was strictly chosen based on the SRCA and seven of the 24 patients (29%) whose treatment was based on physician's choice survived at least 3 years. Our conclusion is that the SRCA is of limited value in the selection of second-line chemotherapy in recurrent ovarian cancer. PMID- 1899197 TI - Crystal structure of the ternary complex of ribulose-1,5-bisphosphate carboxylase, Mg(II), and activator CO2 at 2.3-A resolution. AB - The activated ternary complex, enzyme-CO2-Mg(II), of the dimeric ribulose-1,5 bisphosphate carboxylase/oxygenase from Rhodospirillum rubrum can be prepared in the same crystal form that was used for the crystallographic structure determination of the native nonactivated enzyme (Schneider, G., Branden, C.-I., & Lorimer, G. (1986) J. Mol. Biol. 187, 141-143). The three-dimensional structure of the activated enzyme has been determined to a nominal resolution of 2.3 A by protein crystallographic methods. The activator CO2 forms a carbamate with Lys191, located at the bottom of the funnel-shaped active site. In both subunits, this labile adduct is stabilized by a Mg(II) ion, bound to the carbamate and the side chains of Asp193 and Glu194. One solvent molecule was found within the first coordination sphere of the metal ion. The metal-binding site in ribulose-1,5 bisphosphate carboxylase consists thus of at least three protein ligands, all located on loop 2 of the beta/alpha barrel. One additional metal ligand, the side chain of the conserved Asn111, was observed close to the Mg(II) ion in the B subunit. Other structural differences at the active site between the activated and nonactivated enzyme are limited to side-chain positions. Nevertheless, it is obvious that the hydrogen-bonding pattern in the vicinity of the activator site is completely altered. PMID- 1899198 TI - Purification and characterization from rat liver cytosol of a GDP dissociation inhibitor (GDI) for liver 24K G, a ras p21-like GTP-binding protein, with properties similar to those of smg p25A GDI. AB - A regulatory protein for a liver GTP-binding protein (G protein) with a molecular weight value of 24,000 (24K G), which we have recently purified, was purified to near-homogeneity from rat liver cytosol and characterized. This regulatory protein, designated here as GDP dissociation inhibitor for 24K G (24K G GDI), inhibited the dissociation of GDP from and the subsequent binding of GTP to 24K G. 24K G GDI was inactive for other ras p21/ras p21-like small G proteins including c-Ha-ras p21, rhoB p20, smg p21B, and smg p25A. 24K G was, however, recognized by bovine brain smg p25A GDI which regulated the GDP/GTP exchange reaction of smg p25A. By analyses of sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis (PAGE), immunoblotting with anti-smg p25A GDI antibody, two dimensional PAGE, and C4 column chromatography, 24K G GDI showed physical properties very similar to those of smg p25A GDI. The peptide map and the partial amino acid sequences of 24K G GDI were not identical with those of smg p25A GDI. Among the 83 residues, 2 amino acids were different between rat liver 24K G GDI and bovine brain smg p25A GDI. These results indicate that there is a specific regulatory protein for 24K G, 24K G GDI, in rat liver cytosol and that 24K G GDI has close similarity to smg p25A GDI. PMID- 1899199 TI - Chemical mechanism and rate-limiting steps in the reaction catalyzed by Streptococcus faecalis NADH peroxidase. AB - The pH dependence of the kinetic parameters V, V/KNADH, and V/KH2O2 has been determined for the flavoenzyme NADH peroxidase. Both V/KNADH and V/KH2O2 decrease as groups exhibiting pK's of 9.2 and 9.9, respectively, are deprotonated. The V profile decreases by a factor of 5 as a group exhibiting a pK of 7.2 is deprotonated. Primary deuterium kinetic isotope effects on NADH oxidation are observed on V only, and the magnitude of DV is independent of H2O2 concentration at pH 7.5. DV/KNADH is pH independent and equal to 1.0 between pH 6 and pH 9.5, but DV is pH dependent, decreasing from a value of 7.2 at pH 5.5 to 1.9 at pH 9.5. The shape of the DV versus pH profile parallels that observed in the V profile and yields a similar pK of 6.6 for the group whose deprotonation decreases DV. Solvent kinetic isotope effects obtained with NADH or reduced nicotinamide hypoxanthine dinucleotide as the variable substrate are observed on V only, while equivalent solvent kinetic isotope effects on V and V/K are observed when H2O2 is used as the variable substrate. In all cases linear proton inventories are observed. Primary deuterium kinetic isotope effects on V for NADH oxidation decrease as the solvent isotopic composition is changed from H2O to D2O. These data are consistent with a change in the rate-limiting step from a step in the reductive half-reaction at low pH to a step in the oxidative half reaction at high pH. Analysis of the multiple kinetic isotope effect data suggests that at high D2O concentrations the rate of a single proton transfer step in the oxidative half-reaction is slowed. These data are used to propose a chemical mechanism involving the pH-dependent protonation of a flavin hydroxide anion, following flavin peroxide bond cleavage. PMID- 1899200 TI - Identification of the serine residue phosphorylated by protein kinase C in vertebrate nonmuscle myosin heavy chains. AB - Two-dimensional mapping of the tryptic phosphopeptides generated following in vitro protein kinase C phosphorylation of the myosin heavy chain isolated from human platelets and chicken intestinal epithelial cells shows a single radioactive peptide. These peptides were found to comigrate, suggesting that they were identical, and amino acid sequence analysis of the human platelet tryptic peptide yielded the sequence -Glu-Val-Ser-Ser(PO4)-Leu-Lys-. Inspection of the amino acid sequence for the chicken intestinal epithelial cell myosin heavy chain (196 kDa) derived from cDNA cloning showed that this peptide was identical with a tryptic peptide present near the carboxyl terminal of the predicted alpha-helix of the myosin rod. Although other vertebrate nonmuscle myosin heavy chains retain neighboring amino acid sequences as well as the serine residue phosphorylated by protein kinase C, this residue is notably absent in all vertebrate smooth muscle myosin heavy chains (both 204 and 200 kDa) sequenced to date. PMID- 1899201 TI - Cardioplegia controversies. PMID- 1899203 TI - Weaning from ventilation after cardiopulmonary bypass: evaluation of a non invasive technique. AB - Weaning of patients from IPPV after cardiopulmonary bypass (CPB) is usually monitored by frequent arterial blood gas analysis. Non-invasive monitoring has the advantage of providing continuous and instantaneous information and could reduce the frequency of arterial blood gas sampling. Twenty patients were studied to determine the reliability of capnometry and pulse oximetry in this situation. The effects of hypothermia and moderate haemodynamic instability were examined. A further 40 patients were then weaned using non-invasive monitoring. Correlation between PaCO2 and PETCO2 was 0.64-0.79 for the mass spectrometer and 0.67-0.81 for the infra-red analyser. No clinical problems arose. The detection rate for mild hypercarbia was 78.6 per cent and 50 per cent for hypoxia. Possible reasons for this are discussed. Once CO2 and O2 gradients are established, pulse oximetry and capnometry provide sufficiently reliable monitoring to enable weaning from IPPV, with the advantage of continuous display, and allow a reduction in the use of arterial blood gas analyses. PMID- 1899202 TI - Diaphragmatic function during sevoflurane anaesthesia in dogs. AB - The effect of increasing the concentration of sevoflurane anaesthesia on diaphragmatic function was investigated in six mechanically ventilated dogs. Diaphragmatic function was assessed by measuring the transdiaphragmatic pressure (Pdi) generated during bilateral supramaximal stimulation of the cervical phrenic nerves at frequencies of 0.5, 10, 20, 50, and 100 Hz under quasi-isometric conditions. Measurements were performed at 1, 1.5 and 2 MAC concentrations after maintaining stable conditions for one hour. The Pdi-stimulus frequency relationship was compared at each anaesthetic concentration. The sequence of changing anaesthetic depth was altered in random fashion among animals. The Pdi amplitude generated by single twitch (0.5 Hz) was unchanged at the three concentrations. In addition, no change in Pdi during 10, 20, 50 Hz stimulation was noted at any of the three levels of anaesthesia. By contrast, Pdi with 100 Hz stimulation during 2 MAC sevoflurane exposure (28.1 +/- 5.0 cmH2O) decreased below Pdi levels seen at 1 and 1.5 MAC (35.3 +/- 4.3 cmH2O and 31.5 +/- 4.3 cmH2O, respectively) (P less than 0.05). From these results, we conclude that sevoflurane impairs diaphragmatic function in deep anaesthesia. PMID- 1899204 TI - Transcranial Doppler: response of cerebral blood-flow velocity to carbon dioxide in anaesthetized children. AB - To determine the effect of carbon dioxide on the cerebral circulation in anaesthetized infants and children, 13 healthy children, ASA physical status I or II, between three months and seven years of age and scheduled for urologic surgery, were studied. Anaesthesia was induced with thiopentone and vecuronium. After tracheal intubation, anaesthesia was maintained with 70 per cent nitrous oxide in oxygen, fentanyl 2 micrograms.kg-1, vecuronium 0.05 mg.kg-1 and 0.8-1.0 per cent end-tidal isoflurane. A caudal block was performed before surgery. Systolic arterial pressure, heart rate, oxygen saturation, temperature, and end tidal isoflurane were maintained constant. Ventilation was adjusted to achieve an end-tidal PCO2 (PETCO2) of 20 mmHg. The PETCO2 was then randomly adjusted between 20 and 80 mmHg by the addition of carbon dioxide from an exogenous source. Cerebral blood flow velocity increased logarithmically and directly with the PETCO2 (r2 = 0.56). There were no complications associated with the use of transcranial Doppler sonography. These data indicate that CO2 has a direct effect on the velocity of blood in the middle cerebral artery in infants and children anaesthetized with isoflurane. PMID- 1899205 TI - Myocardial oedema and ventricular function after cardioplegia with added mannitol. AB - Myocardial oedema may contribute to the impaired myocardial performance which commonly follows open heart surgery with cardioplegia-induced cardiac arrest. The rate of oedema formation during crystalloid cardioplegia and the relation of this to changes in ventricular compliance and ventricular function following reperfusion were studied using an isolated rabbit heart preparation. Myocardial tissue water content increased during cardioplegic arrest and the water content prior to reperfusion demonstrated an inverse correlation with ventricular function after reperfusion. In further studies the effect of adding mannitol to a standard crystalloid cardioplegic solution was investigated. The preparations were divided into two groups: nine were administered a standard cardioplegic solution (Plegisol*) (control group) and a further eight were administered the same solution mixed with mannitol to adjust the osmotic pressure to 360 mOsmol.L 3 (mannitol group). The mannitol group demonstrated less increase in RV water content and superior LV dP/dtmax following reperfusion. It is concluded that mannitol enhances protection of the myocardium during cardioplegic cardiac arrest. PMID- 1899206 TI - Clinical evaluation of closed-loop control of blood pressure in seriously ill patients. AB - OBJECTIVE: To compare the effectiveness of a new method of closed-loop (automatic) control of BP with usual manual control. DESIGN: Within-subject crossover trial. SETTING: General and open heart ICUs in a university teaching hospital. PATIENTS: Convenience sample of 74 seriously ill patients aged 17 to 88 yr. Twenty had hypertension: postoperative (n = 7), neurologic damage (n = 6), miscellaneous (n = 7), and were prescribed nitroprusside (n = 11) or nitroglycerin (n = 9). Fifty-four had hypotension: septic (n = 33), other (n = 21), and were prescribed norepinephrine (n = 30), dopamine (n = 11), epinephrine (n = 8), or dobutamine (n = 5). An additional 21 trials were omitted from analysis because of technical (n = 7), clinical (n = 1), or drug-related problems (n = 13). INTERVENTION: Closed-loop and manual drug administrations 1-hr were studied during periods in each patient. The target and observed mean arterial pressure (MAP) and drug infusion rate were recorded electronically every 30 sec. MAIN OUTCOME MEASUREMENTS: Time taken to achieve initial control (min); fidelity of control (the integral of size and duration of error from target MAP +/- 10% in mm Hg.hr/hr); and average drug dose administered (microgram/min as % maximum possible per drug). RESULTS: Compared with manual control, closed-loop achieved faster initial control (log-rank chi 1 = 5.04, p less than .05) and greater fidelity (mean 1.37 vs. 2.36; F = 7.15, p less than .01). There was no difference in average drug dose administered. There was uniformity in the efficacy advantage of closed-loop drug administration across drugs and patient classifications. CONCLUSION: The new closed-loop system is more effective than the usual manual control in managing acute BP disturbances in the seriously ill patient. PMID- 1899207 TI - Aortic root blood flow increases after pancuronium in neonates with hyaline membrane disease. AB - OBJECTIVE: To determine the effects of muscle paralysis on aortic root blood flow in preterm infants with hyaline membrane disease. DESIGN: Each patient served as his/her own control in a prospectively controlled trial. SETTING: Neonatal ICU in a university hospital. PATIENTS: Ten ventilator-dependent preterm infants weighing 800 to 2820 g, 0 to 8 days of age, with hyaline membrane disease and seven control patients. INTERVENTIONS: Noninvasive measurement of aortic root blood flow by Doppler echocardiography 30 min before and 60 min after respiratory paralysis with 0.1 to 0.5 mg/kg of iv pancuronium, or following ventilator changes in control subjects. RESULTS: Mean aortic root blood flow increased significantly (p less than .001), from 212 to 276 mL/min.kg, accompanied by significant increases in stroke volume and heart rate. CONCLUSIONS: Pancuronium bromide may have a direct beneficial effect on the circulation of preterm infants with hyaline membrane disease. PMID- 1899208 TI - Tissue oxygenation in hemorrhagic shock measured as transcutaneous oxygen tension, subcutaneous oxygen tension, and gastrointestinal intramucosal pH in pigs. AB - BACKGROUND AND METHODS: Tissue oxygenation, measured in peripheral tissue as transcutaneous PO2 (PtCO2) and subcutaneous PO2, was compared with the oxygenation in GI mucosa, which was measured as intramucosal wall pH (pHi), during experimental hemorrhagic shock and resuscitation in pigs. The pigs were hemorrhaged stepwise to a BP of 80 and 45 mm Hg, followed by retransfusion. PtCO2 was measured in the groin and subcutaneous PO2 was measured in the hip region. Intraluminal PCO2 was measured in the stomach, in the small intestine, and the sigmoid colon using silicone catheters. A simultaneous determination of arterial blood HCO3 concentration allowed pHi to be calculated using Henderson-Hasselbalch equation. Cardiac output was determined by thermodilution, and oxygen delivery (DO2) was calculated. RESULTS: Early indications of shock were decreases in PtCO2 and intestinal pHi (p less than .01). All measured variables decreased at the second step of bleeding. PtCO2 and subcutaneous PO2 was correlated to DO2 through the entire experiment (r2 = .25 and .49, respectively). Also, the pHi of the small intestine and the sigmoid colon correlated with DO2 (r2 = .36 and .25, respectively). PtCO2 and subcutaneous PO2 correlated with pHi in the small intestine and sigmoid colon. CONCLUSIONS: PtCO2 and pHi in the small intestine and sigmoid colon were the variables that most rapidly indicated blood volume loss. Subcutaneous PO2 and PtCO2, and small intestine and sigmoid colon pHi were correlated to total body oxygen transport. Peripheral tissue perfusion followed intestinal perfusion to some extent. PMID- 1899209 TI - Reversible impairment of myocardial contractility due to hypercarbic acidosis in the isolated perfused rat heart. AB - BACKGROUND AND METHODS: Striking increases in PCO2 of the myocardium have recently been documented during cardiac arrest. The purpose of the present study was to investigate selective effects of hypercarbia as distinct from acidosis on left ventricular contractile function and oxygen utilization. An isolated, spontaneously beating rat heart preparation was utilized. The perfusate was equilibrated with gases containing 5%, 10%, 20%, and 30% CO2. In a subset of experiments, the [H+] was adjusted independently of PCO2 by decreasing the concentration of HCO3-. RESULTS: When the PCO2 of the perfusate was progressively increased from 36 to 146 torr (4.8 to 29.5 kPa), the left ventricular systolic pressure (LVSP) generated by the isolated heart and the maximum rate of pressure change in the left ventricle (dP/dt) were decreased to 20% of their control values. However, comparable acidosis in the absence of hypercarbia produced only minimal decreases in the LVSP or dP/dt such that contractility remained at greater than or equal to 88%. Increases in the perfusate PCO2 but not in the perfusate H+ were highly correlated with decreases in both myocardial contractility and oxygen consumption (r2 = .88). CONCLUSION: Hypercarbia rather than acidosis accounts for decreased contractility and oxygen utilization in the isolated perfused rat heart. PMID- 1899211 TI - Rapid normalization of serum albumin with modified total parenteral nutrition solutions. PMID- 1899210 TI - Prolonged hemorrhagic shock does not impair regeneration of plasma coagulant masses in the rabbit. AB - BACKGROUND AND METHODS: Twelve adult male albino rabbits were assigned alternately to normotensive and hypotensive groups to assess the effect of hypovolemic shock on spontaneous correction of dilutional coagulopathy. All animals underwent dilutional exchange transfusion with 200 mL of rabbit RBCs and 5% human albumin. Half the animals were then acutely hemorrhaged and subsequent aliquots of blood removed as needed to maintain the mean arterial pressure at 40 mm Hg. RESULTS: By 6 hr after production of dilutional coagulopathy, masses and plasma concentrations of fibrinogen and Factor II had increased modestly but significantly, and Factor VII mass and concentration and in vitro coagulation had returned almost to normal; plasma volume was unchanged in the normotensive animals. In the hypovolemic shock animals, where coagulant mass regeneration was as rapid as in the normotensive animals, a doubling of total plasma volume (p less than .01) prevented the concentrations of fibrinogen and Factor II, and hence the coagulation times, from improving. CONCLUSIONS: Dilutional coagulopathy corrects spontaneously within hours. Normovolemic shock prolongs dilutional coagulopathy not by impairment of factor regeneration but because of further (internal) dilution due to plasma expansion. Rapid correction of dilutional coagulopathy is likely to necessitate cryoprecipitate administration. PMID- 1899212 TI - Interpretation of PCO2 in the asthmatic patient. PMID- 1899213 TI - Influence of noninvasive positive pressure ventilation on inspiratory muscles. AB - Intermittent positive pressure ventilation reduces inspiratory muscle electromyographic activity among patients with restrictive ventilatory failure. It has therefore been suggested that the reduction of energy expenditure at night could result in improved inspiratory muscle function during the day. Reported successes with nocturnal ventilation have not included measurements of inspiratory muscle endurance. We therefore electively ventilated six (five female, one male) patients (mean +/- SD) aged 36 +/- 13 years in whom respiratory failure (room air PaCO2, 60 +/- 13 mm Hg; PaO2, 44 +/- 11 mm Hg; SaO2, 75 +/- 12 percent) was consequent on restrictive ventilatory disease (vital capacity, 25 +/ 7 percent predicted; FEV1/FVC, 81 +/- 12 percent; total lung capacity, 40 +/- 5 percent predicted; MIPRV -42 +/- 10 cm H2O; MEP, 81 +/- 28 cm H2O). Positive pressure ventilation was administered with a customized closely fitting nasal mask attached to a volume-cycled pressure-limited ventilator. Full respiratory polysomnographic measurements as well as arterial blood gases, pulmonary function, distance walked in six minutes, and inspiratory muscle endurance were measured at baseline and after 3 and 14 months of ventilation. Ventilation improved saturation (baseline on O2; SWS 87 +/- 10, REM 79 +/- 14, ventilator on R/A; SWS 90 +/- 6, REM 89 +/- 5 percent) and transcutaneous Pco2 (baseline on O2; SWS 85 +/- 26, REM 94 +/- 39, ventilator on R/A; SWS 53 +/- 9, REM 58 +/- 9 mm Hg). During ventilation, the quantity and distribution of sleep was similar to that observed prior to ventilation. Daytime gas exchange improved as did the six minute walking test (initial test = 429 +/- 120 m, three months after ventilation = 567 +/- 121 m), both of these improvements being sustained at 14 months. Inspiratory muscle endurance measured using a pressure threshold load (mean mouth pressure = 45 percent MIPRV) improved from 7.1 +/- 3.4 minutes at baseline to 14.8 +/- 7.6 minutes at 3 months, an improvement sustained at 14 months. There was no change in measured lung volumes or respiratory muscle strength. We conclude that the improvement in nocturnal gas exchange, daytime functioning, and arterial blood gases resulting from nocturnal positive pressure ventilation is associated with an increase in inspiratory muscle endurance sustained at 14 months. PMID- 1899214 TI - Diaphragmatic performance during recovery from acute ventilatory failure in Guillain-Barre syndrome and myasthenia gravis. AB - Diaphragmatic muscle performance during acute ventilatory failure due to Guillain Barre syndrome and myasthenia gravis was assessed to evaluate (1) diaphragmatic function during weaning from ventilatory support and (2) diaphragmatic tension time integral (TTdi) during ventilatory failure. We used a multilumen nasogastric tube and a pneumotachograph to measure transdiaphragmatic pressure per breath (Pdi), maximum transdiaphragmatic pressure (Pdimax), tidal volume (VT), and inspiratory time fraction during 74 spontaneous breathing trials in nine patients. Diaphragmatic performance was poor in all patients. The Pdi, Pdimax, and VT improved significantly, but values for Pdi and Pdimax remained low even after weaning. Improvement in Pdimax was the best predictor of recovery (r = 0.48; p less than 0.001). Maximal inspiratory force correlated with Pdimax (r = 0.48; p less than 0.005), but FVC did not. The TTdi rarely exceeded the expected fatigue threshold of 0.15 in spite of the patient's inability to sustain ventilation. Although our patients demonstrated diaphragmatic weakness, TTdi did not demonstrate diaphragmatic fatigue. PMID- 1899215 TI - Vasoactive intestinal polypeptide and thyrotropin-releasing hormone stimulate newly synthesized, not stored, prolactin. AB - Experiments were designed to determine whether vasoactive intestinal polypeptide (VIP), reported to stimulate basal PRL secretion, affects PRL processing by lactotrophs. Initially, rat anterior pituitary quarters were incubated for 2 h with [3H]leucine, with and without 10(-5) M VIP, and immunoreactive and immunoprecipitable rPRL were measured during 56 mM KCl perifusion to determine total and 3H-labeled PRL, respectively. Inclusion of VIP increased immunoreactive PRL (P less than 0.05), decreased immunoprecipitable PRL (P less than 0.01), and, therefore, decreased the specific activity of labeled PRL (P less than 0.001). These results suggested an enhanced release of newly synthesized PRL before KCl depolarization, thus decreasing the release of labeled PRL. To discriminate between the two PRL pools, newly synthesized and storage, pituitary quarters were incubated with and without 10(-5) M VIP for 4 h with [14C]leucine, 2 h in cold medium and 2 h with [3H]leucine. Immunoprecipitable PRL was measured during perifusion with 56 mM KCl. Data were depicted as the 3H/14C disintegrations per min ratio of PRL released/3H/14C disintegrations per min of total tissue to account for any differences in tissue labeling. This ratio was greater for tissue labeled in the presence of VIP (P less than 0.002). To determine whether VIP, as a secretagogue, differentiates between the newly synthesized and storage pools, VIP was added after pulse chase, as previously described. No preferential release was observed between the two groups. Finally, using the same [3H]- and [14C]leucine-labeling protocol with and without 10(-5) M VIP, tissue was perifused with medium 199 for 1 h, with 10(-5) M TRH for 30 min, with medium 199 for 30 min, and with 56 mM KCl for 1 h. Inclusion of VIP increased the 3H/14C released/3H/14C total tissue ratio during basal perifusion (P less than 0.04) and TRH exposure (P less than 0.05). Within the control group, the TRH ratio was greater than basal (P less than 0.003). These experiments suggest that newly synthesized PRL is preferentially secreted over stored PRL from tissue incubated with VIP during pulse-chase labeling; however, addition of VIP as a secretagogue did not affect either PRL pool preferentially. PMID- 1899216 TI - The radioimmunoassay of follicle-stimulating hormone (FSH)-suppressing protein (FSP): stimulation of bovine granulosa cell FSP secretion by FSH. AB - A RIA for bovine (b) FSH-suppressing protein (FSP) was developed using an antiserum raised in a rabbit to purified 39-kDa bFSP, iodinated 35-kDa FSP as tracer, and purified 35-kDa bFSP as standard. Purified 35-kDa FSP was iodinated using the iodogen procedure, and the iodinated FSP was purified by dye affinity chromatography. After a logit log-dose transformation of the dose-response curves, parallel displacement lines were observed between 31-, 35-, and 39-kDa FSP, bovine follicular fluid, bovine granulosa cell culture medium, and medium from bovine granulosa cells stimulated with bFSH. The specificity of the assay was investigated by comparing the immunoassay levels of FSP with in vitro bioassay levels based on the ability of FSP/inhibin to suppress FSH in rat anterior pituitary cell cultures in fractions obtained throughout the purification procedure of FSP from bovine follicular fluid. This demonstrated that 1) the FSP immunoactivity was associated with in vitro bioactivity in all fractions of the purification procedure; 2) a number of inhibin-related and other proteins showed low (less than 0.5%) or nondetectable cross-reactivity in the RIA; and 3) the in vitro biological to immunological ratios for 31-, 35-, and 39 kDa FSP were similar, indicating that the RIA detects all forms of purified bFSP. The secretion of FSP by bovine granulosa cells in culture was investigated in the presence and absence of bFSH and bLH, respectively. FSP production was proportional to granulosa cell number and decreased from highest levels at 24 h to lowest levels at 96 h of culture. The addition of either bFSH or 8-bromo-cAMP to the culture medium stimulated FSP production by a factor of 2-3 at 48 and 72 h of culture, while the addition of bLH had no effect on FSP production. Theca interna tissue cultured under the same conditions did not produce FSP. In contrast to FSP, stimulation of bovine granulosa cells with bFSH or bLH had no effect on inhibin production during the 96 h of culture, while the addition of bFSH and bLH caused a stimulation of progesterone production at 48 and 72 h of culture. It is concluded that 1) the RIA described here is specific for all mol wt forms of bFSP; 2) FSP was secreted by bovine granulosa cells and not thecal cells in vitro; and 3) FSP secretion by bovine granulosa cells in vitro is regulated by bFSH and not bLH. PMID- 1899217 TI - In vivo comparison of the follicle-stimulating hormone-suppressing activity of follistatin and inhibin in ovariectomized rats. AB - The present study was performed to compare and contrast the effects of two gonadal polypeptides, inhibin and follistatin, on ovariectomy-induced hypersecretion of FSH and LH. Ovariectomies were performed 1 week before study. Follistatin was purified from porcine follicular fluid, and human inhibin A was produced by recombinant DNA technology. On the day of study, a blood sample was taken from intraatrial cannulae inserted on the previous day, the materials were injected, and additional blood samples were taken at various times thereafter. Serum FSH and LH levels were determined by RIA. Both follistatin and inhibin exhibited dose-dependent suppression of circulating FSH but not LH levels, with initial decreases in FSH levels by both materials observed between 2-4 h post injection. Maximal suppression of FSH by each polypeptide occurred between 4-6 h depending on dose. Based on the dose-response relationships, it was determined that inhibin was approximately five times as potent as follistatin in suppressing FSH release. However, despite the greater biopotency of inhibin than follistatin, the duration of action of even the highest dose of inhibin (50 micrograms) was between 4-9 h, whereas the duration of FSH-suppressing activity by the two highest doses of follistatin (40 and 80 micrograms) was between 10-21 h. Data obtained from a second experiment conducted to examine the effects of inhibin and follistatin on anterior pituitary gonadotropin responses to LHRH were consistent with in vitro data showing direct pituitary effects of the gonadal polypeptides. Collectively, these results demonstrate that both purified porcine follistatin and recombinant human inhibin A profoundly suppress serum FSH levels in a dose- and time-dependent manner, with inhibin being more potent in this regard. Whereas the onset of action is similar for the two polypeptides, the duration of action of follistatin is longer than that for inhibin, suggesting, among other factors, different metabolic clearance rates or different pretranscriptional mechanisms of action of follistatin and inhibin. PMID- 1899218 TI - Canatoxin, a plant protein, induces insulin release from isolated pancreatic islets. AB - Canatoxin (CNTX), the toxic protein purified from Canavalia ensiformis, has been shown to induce secretion from different cellular systems through a mechanism involving a lipoxygenase-mediated pathway. Here it is shown that CNTX causes insulin release from isolated rat pancreatic islets. This effect is time and dose dependent, occurs in the absence as well in the presence of glucose, and is markedly reduced at lower temperatures (15 C). At 1-2 microM, the insulinotropic effect of CNTX is equivalent to that of 20 mM glucose, and the two responses are not additive. The stimulatory effect of CNTX is not caused by a toxic or lytic effect of the toxin on the islets, since islets once exposed to CNTX are able to respond a new insulinotropic stimulus. The phospholipase inhibitor mepacrine impairs insulin release induced by either CNTX or glucose. Indomethacin, an inhibitor of the cyclooxygenation of arachidonic acid, fails to affect insulin release, but two lipoxygenase inhibitors block it, and epinephrine reduces it. These data suggest that CNTX may act on islets through the same pathway as that used by glucose, with both effects being mediated by lipoxygenases. PMID- 1899219 TI - Interrelationship between the actions of testosterone and primate Sertoli cell inhibin in the control of gonadotropin secretion by cultured pituitary cells. AB - There is accumulating evidence that the differential regulation of LH and FSH secretion in the male is partly accomplished by the direct actions of testosterone (T) and inhibin on the pituitary. The present study was designed to examine the interaction between T and inhibin, in the presence and absence of GnRH, using dispersed pituitary cells in monolayer culture and cells perifused with pulses of GnRH from intact, 2-week castrated, and castrated T-replaced young adult male rats. The effect of partially purified inhibin from primate Sertoli cell culture medium (pSCI) to suppress basal FSH secretion was similar with pituitary cells from intact and castrated rats. T increased basal FSH secretion in the presence or absence of pSCI but did not alter the dose-dependent suppression of FSH by pSCI with cells from either intact or castrate rats. Castration increased basal FSH and LH secretion, whereas only basal FSH release was increased with cells from T-replaced castrates. T pretreatment increased the action of pSCI to suppress GnRH-stimulated FSH and LH release from perifused pituitary cells. These data indicate that T and inhibin exert opposite but independent effects on basal FSH release. The action of inhibin to suppress basal FSH secretion is not impaired by the absence of T and inhibin subsequent to castration. By contrast, the actions of T and inhibin to suppress GnRH-stimulated gonadotropin secretion are coordinated and interrelated. PMID- 1899221 TI - The suckling stimulus increases the responsiveness of mammotropes located exclusively within the central region of the adenohypophysis. AB - Studies from several groups, including our own, have shown that the suckling stimulus increases the responsiveness of pituitary cells to PRL-releasing stimuli. These findings, when viewed in light of differences in PRL cell responsiveness from one pituitary region to another, raised the possibility that suckling may influence responsiveness of cells in only a specific portion of the gland rather than in the entire pituitary. To address this issue, we evaluated cell responsiveness by performing plaque assays [with and without TRH, Angiotensin II (AII), and dopamine] on cells from two different regions of pituitaries from suckled and nonsuckled rats. These pituitary regions consisted of the inner zone, which is a central area proximate to the neurointermediate lobe, and an outer zone, which encompasses the remaining peripheral area of the anterior lobe. We found that inner zone cells from nonsuckled animals were highly responsive to dopamine and relatively unresponsive to TRH and AII. However, after suckling, a complete shift occurred with inner zone cells becoming sensitive to TRH and AII and resistant to dopamine. In contrast to these inner zone alterations, outer zone cells did not change after suckling, but remained responsive to TRH and AII and unresponsive to dopamine. Our results demonstrate clearly that suckling-induced alterations in PRL cell responsiveness to certain modulatory agents can be attributed to a discrete subpopulation of cells located in a specific region of the pituitary. PMID- 1899220 TI - Thyroxine and 3,3',5-triiodothyronine are glucuronidated in rat liver by different uridine diphosphate-glucuronyltransferases. AB - Male Wistar rats were treated with 50 mg 3,3',4,4'-tetrachlorobiphenyl (TCB)/kg BW or vehicle. After 4 days, the livers were isolated and perfused for 90 min with 2 nM [125I]T3 or 10 nM [125I]T4 in Krebs-Ringer medium containing 1% albumin. Deiodination and conjugation products and remaining substrates were determined in bile and medium samples by Sephadex LH-20 chromatography and HPLC. TCB treatment did not affect hepatic uptake and metabolism of T3. However, biliary excretion of T4 glucuronide was strongly increased by TCB, resulting in an augmented T4 disappearance from the medium, although initial hepatic uptake of T4 was not altered. Measurement of the microsomal UDP-glucuronyltransferase (UDPGT) activities confirmed that T4 UDPGT was induced by TCB, whereas T3 glucuronidation was unaffected. T3 UDPGT activity showed a discontinuous variation, which completely matched the genetic heterogeneity in androsterone glucuronidation in Wistar rats. These results indicate that different isozymes catalyze the glucuronidation of T3 and T4. PMID- 1899222 TI - Gonadotropin-releasing hormone overrides the negative effect of reduced dietary energy on gonadotropin synthesis and secretion in ewes. AB - During prolonged periods of reduced dietary energy, there is a reduction in secretion of LH in females. To test the hypothesis that decreased secretion of LH is due to reduced secretion of GnRH, 18 ovariectomized ewes were fed either a low energy diet (LOW, 60% of the National Research Council recommendations, n = 12) or a normal diet, (control, n = 6), for 127 days. Each ewe received basal levels (approximately 5 pg/ml) of estradiol via sc Silastic implants. After 127 days, serum concentrations of FSH and LH were reduced (P less than 0.05) by 63% and 77%, respectively in LOW ewes compared to control ewes. Pituitary concentrations of FSH and LH in LOW ewes also were reduced by 56% and 80%, respectively. Compared to levels in control ewes, concentrations of messenger RNAs for alpha-, FSH beta-, and LH beta-subunits were reduced by 75%, 76%, and 91%, respectively. Pulsatile administration of GnRH (250 ng/2 h) for three weeks to LOW ewes restored each of the parameters to levels not different from those in controls. By the end of the study, serum concentrations of GH in all LOW animals had risen dramatically, but not in control ewes. Therefore, it appears that exogenous GnRH is capable of restoring synthesis and secretion of gonadotropins in ewes receiving low-energy diets. These results provide support for the hypothesis that reduced dietary energy results in decreased secretion of GnRH. PMID- 1899223 TI - Prostaglandin F2 alpha-induced calcium transient in ovine large luteal cells: II. Modulation of the transient and resting cytosolic free calcium alters progesterone secretion. AB - A previous study demonstrated that prostaglandin F2 alpha (PGF2 alpha) stimulates a transient increase in cytosolic free Ca2+ levels [( Ca2+]i) in ovine large luteal cells. In the present study, the magnitude of the PGF2 alpha (0.5 microM) induced calcium transient in Hanks' medium (87 +/- 2 nM increase above resting levels) was reduced (P less than 0.05) but not completely eliminated in fura-2 loaded large luteal cells incubated in Ca2(+)-free or phosphate- and carbonate free medium (10 +/- 1 nM, 32 +/- 6 nM, above resting levels; respectively). Preincubation for 2 min with 1 mM LaCl3 (calcium antagonist) eliminated the PGF2 alpha-induced calcium transient. The inhibitory effect of PGF2 alpha on secretion of progesterone was reduced in Ca2(+)-free medium or medium plus LaCl3. Resting [Ca2+]i levels and basal secretion of progesterone were both reduced (P less than 0.05) in large cells incubated in Ca2(+)-free medium (27 +/- 4 nM; 70 +/- 6% control, respectively) or with 5 microM 5,5'-dimethyl bis-(O-aminophenoxy)ethane N,N,N'N'-tetraacetic acid (40 +/- 2 nM; 49 +/- 1% control; respectively). In addition, secretion of progesterone was inhibited (P less than 0.05) by conditions that increased (P less than 0.05) [Ca2+]i; that is LaCl3 ([Ca2+]i, 120 +/- 17 nM; progesterone, 82 +/- 8% control) and PGF2 alpha ([Ca2+]i, 102 +/- 10 nM; progesterone, 82 +/- 3% control). In small luteal cells, resting [Ca2+]i levels and secretion of progesterone were reduced by incubation in Ca2(+)-free Hanks ([Ca2+]i, 28 +/- 2 nM; progesterone, 71 +/- 6% control), however, neither LaCl3 nor PGF2 alpha increased [Ca2+]i levels or inhibited secretion of progesterone. The findings presented here provide evidence that extracellular as well as intracellular calcium contribute to the PGF2 alpha-induced [Ca2+]i transient in large cells. Furthermore, whereas an adequate level of [Ca2+]i is required to support progesterone production in both small and large cells, optimal progesterone production in large cells depends upon an appropriate window of [Ca2+]i. PMID- 1899224 TI - Hypophysectomy inhibits the synthesis of tumor necrosis factor alpha by rat macrophages: partial restoration by exogenous growth hormone or interferon gamma. AB - We recently demonstrated that GH and interferon-gamma (IFN gamma) act in a similar manner to prime macrophages in vitro and in vivo for enhanced superoxide anion release. In this report we investigated the physiological role of the pituitary gland and GH in in vivo priming of resident peritoneal macrophages for the synthesis of tumor necrosis factor-alpha (TNF alpha) in vitro. Compared to normal rats, hypophysectomized animals had an 83% reduction in macrophage production of TNF alpha after in vitro stimulation with lipopolysaccharide. Sham operation had no significant effect on the ability of macrophages to secrete TNF alpha in response to lipopolysaccharide. Both native pituitary-derived porcine GH (48 micrograms/rat.9 days) and native pituitary-derived rat GH (96 micrograms/rat.9 days) more than tripled the in vitro production of TNF alpha by macrophages from hypophysectomized rats (342 and 358 vs. 112 U/mg protein for placebo-treated rats, respectively). Each of these preparations of GH also increased growth more than 6-fold in hypophysectomized rats (32 and 30 g vs. 5 g in placebo controls). Heat inactivation of native pituitary-derived porcine GH significantly reduced its in vivo ability to augment both TNF alpha synthesis by macrophages and body growth. Recombinant rat IFN gamma (2000 U/rat.9 days) more than tripled the production of TNF alpha by macrophages from hypophysectomized rats (343 vs. 112 U/mg protein). In contrast to its in vivo effects, addition of GH in vitro to macrophages from hypophysectomized rats did not prime these cells for the synthesis of TNF alpha, indicating an indirect mechanism of action for GH. To further test the biological relevancy of GH with respect to synthesis of TNF alpha, hemorrhagic necrosis of TNF alpha-sensitive murine methyl-cholanthrene induced tumors was assessed in pituitary-intact mice. Native porcine GH (133 micrograms/mouse.7 days) significantly augmented both the necrosis to tumor ratio and the hemorrhage to tumor ratio. These findings establish the physiological relevance of the pituitary gland and GH in the priming of macrophages for TNF alpha synthesis. PMID- 1899226 TI - The andropin gene and its product, a male-specific antibacterial peptide in Drosophila melanogaster. AB - In our study of the cecropin locus in Drosophila we have found a gene for a new peptide, andropin, with antibacterial properties. Transcripts from this gene, Anp, could be detected in newly eclosed males and reached steady-state levels after 1 day. Transcription was strongly induced in response to mating and is strictly confined to the ejaculatory duct of adult males. The deduced peptide sequence reveals a hydrophobic amino terminus with striking similarity to the signal peptide of the cecropins. The sequence of the predicted mature andropin shows no direct homology with the cecropins, but the two peptides may have similar secondary structures. We have synthesized the predicted gene product and shown it to be antibacterial. Crude extracts from male genital tracts show a potent bactericidal activity, and electrophoretic separation revealed at least three antibacterial components, one with the same mobility as the synthetic peptide. It appears that insects have evolved a mechanism for the protection of the seminal fluid and the male reproductive tract against microbial infections. PMID- 1899227 TI - Identification of ecdysone response elements by analysis of the Drosophila Eip28/29 gene. AB - We have identified ecdysone-response elements (EcREs) by studying regulation of the steroid-responsive Drosophila Eip28/29 gene. First, functional assays of deletion mutants identified large sequence regions required for the response; then a blotting method using the specifically labeled steroid receptor as probe identified receptor-binding regions. Three short receptor-binding regions near Eip28/29 have been identified: Prox and Dist [521 and 2295 nucleotides, respectively, downstream of the poly(A) site] are probably required for the Eip28/29 response in cell lines; Upstream (-440) is unnecessary for that response. We have also demonstrated that an EcRE-containing region from hsp27 contains a receptor-binding site. Each of these four receptor-binding regions functions as an EcRE when placed upstream of an ecdysone nonresponsive promoter and each contains an imperfect palindrome, suggesting the consensus 5' RG(GT)TCANTGA(CA)CY-3'. Furthermore, a synthetic 15-bp fragment containing an imperfect palindrome similar to the consensus is a fully functional EcRE. The presence of any of the EcREs leads, in the absence of hormone, to depressed gene expression. When hormone is added, it relieves this repression and causes additional activation. The similarity of the EcRE sequence to response elements for estrogen, thyroid hormone, and retinoic acid receptors suggests that the steroid receptors and their signal transduction mechanisms have been strongly and broadly conserved. PMID- 1899225 TI - TNF induces c-fos via a novel pathway requiring conversion of arachidonic acid to a lipoxygenase metabolite. AB - Tumour necrosis factor (TNF), a lymphokine released by activated macrophages, has diverse effects on a wide variety of cell types. TNF exerts these effects via specific cell surface receptors; however little is known of the biochemical events that ensue. We have shown that TNF rapidly induces the proto-oncogenes c fos and c-jun in the adipogenic TA1 cell line and have used these responses to characterize the intracellular mediators of TNF action. We find that arachidonic acid, which is released in response to TNF, induces c-fos, but not c-jun mRNA in quiescent TA1 cells. Pretreatment of the cells with lipoxygenase inhibitors abolishes the induction of c-fos by TNF, while the induction of c-jun is unaffected; in contrast, a cyclooxygenase inhibitor has no effect on either response. Finally, we have demonstrated that TNF stimulates production of lipoxygenase metabolites in TA1 cells and that one of these, 5-HPETE, induces c fos, but not c-jun. These data suggest that TNF activates two second messenger pathways, one of which is dependent on release of arachidonic acid and its subsequent conversion to a lipoxygenase metabolite. PMID- 1899228 TI - Troponin I is encoded in the haplolethal region of the Shaker gene complex of Drosophila. AB - We have analyzed one of the nine complementation groups that constitute the haplolethal (HL) region of the Shaker gene complex (ShC). Five mutations, including a dominant lethal, define this complementation group: HL I. Mutant phenotypes show abnormal embryogenesis with structural defects in the nervous system and aberrant degeneration of specific adult muscles in addition to altered action potentials. HL I encodes a family of proteins with extensive homology to invertebrate troponin I (TnI). Members of this family are brought about by two alternative and two mutually exclusive exons in conjunction with two differential polyadenylation sites. Transcription analysis indicates that some isoforms are adult specific and others are synthesized throughout development, except during early metamorphosis. Certain isoforms of Drosophila TnI are expressed in specific muscles. The specificity of mutant phenotypes suggests a functional role of particular TnI isoforms in the development and the mature activity of muscle and nervous systems. PMID- 1899229 TI - Modulation of the IgH enhancer's cell type specificity through a genetic switch. AB - Using defined regions of the immunoglobulin heavy-chain enhancer linked to minimal promoters and cDNAs that encode the two helix-loop-helix transcription factors ITF-1 and TFE3, we demonstrate that activity of an otherwise repressed enhancer can be stimulated in nonlymphoid cells. Repression in non-B cells is mediated by the microE5 motif. Derepression occurs at two levels. First, overexpression of ITF-1, and E12/E47-related protein that binds the microE5 motif, leads to transcriptional activation itself. Second, binding of ITF-1 physically displaces a repressor that normally blocks the stimulatory activity of TFE3, which binds the neighboring microE3 motif. TFE3 can only stimulate enhancer activity in the presence of ITF-1 or in the absence of a microE5 motif. Hence, one component of the enhancer's cell type specificity can be artificially modulated through a "genetic switch" in which activity is dictated by the relative levels of ITF-1 and a competing repressor. PMID- 1899230 TI - Fission yeast genes that confer resistance to staurosporine encode an AP-1-like transcription factor and a protein kinase related to the mammalian ERK1/MAP2 and budding yeast FUS3 and KSS1 kinases. AB - Staurosporine, a potent inhibitor of protein kinase C, arrests fission yeast cell elongation specifically at a stage immediately after cell division. We isolated two genes, which, when carried on multicopy plasmids, confer drug resistance in fission yeast. One, spk1+, encodes a protein kinase highly similar (54% identity) to those encoded by the mammalian ERK1/MAP2 kinase and the budding yeast KSS1 and FUS3 genes. It is not essential for vegetative growth of Schizosaccharomyces pombe cells but is required for conjugation. The spk1+ gene product is a 45-kD protein enriched in the nucleus, and its level increases 10-fold after addition of staurosporine. The other gene pap1+ encodes an AP-1-like transcription factor that contains a region rich in basic amino acids followed by a "leucine zipper" motif. The pap1+ gene is required for spk1(+)-conferred staurosporine resistance. These two genes appear to function as a part of the fission yeast growth control pathway. PMID- 1899231 TI - Radiation management of primary carcinoma of the vagina: clinical and histopathological variables associated with survival. AB - Data are presented on 434 patients treated at the Gynecologic Radiotherapy Department of the University of Vienna for invasive primary carcinoma of the vagina between 1952 and 1984; data on 110 patients treated in the last few years are more detailed. In stage I, 5-year survival was 76.7%; in stage II, 44.5%; in stage III, 31%; and in stage IV, 18.2%. The overall uncorrected 5-year survival rate was 39.9%. The disease is primarily one of the elderly as 78% were found to be older than 60 years of age. Younger patients had a 5-year survival of 50%; patients between 61 and 75 years of age, 41.2%; and those 76 years of age or older, 34.3%. Patients with presenting symptoms had a cure rate of 36.9%, whereas 61.1% of asymptomatic cases survived. Best results (60%) were obtained when the lesion was in the upper third of the vagina; only 37% of patients with lesions of the middle third and lower third survived more than 5 years. Well-differentiated tumors were associated with a 5-year survival of 62.5%; and poorly differentiated tumors, with a rate of 34.9%. Our results indicate that stage of disease is the most significant prognostic factor, but age of the patient, location of lesion in the vagina, and differentiation of the tumor influence outcome too. The majority of patients were managed by a combination of external pelvic irradiation and local application of radium. In stage I and II patients treated with radium alone, good results were obtained, but no patient with stage III or IV disease survived 5 years when external irradiation was not performed. PMID- 1899232 TI - Lactobacillus septicemia, an unusual complication during the treatment of metastatic choriocarcinoma. AB - A case of severe Lactobacillus septicemia in a patient treated with chemotherapy because of metastatic choriocarcinoma is described. Although Lactobacillus is a ubiquitous commensal of the female genital tract, no earlier reference was found in the literature. PMID- 1899233 TI - Regulatory control of indoor Rn. AB - Regulation of indoor Rn is explored in the context of cost-effectiveness of regulatory action. Evaluation of cost (i.e., mitigation expenses) and benefits (i.e., savings associated with medical expenses and lost productivity related to lung cancer) at various action levels indicate that regulatory programs would be economically inefficient and unreasonable if standards were established at or below the current EPA action guide (150 Bq m-3 or less). For the approximately 95% of U.S. homes with Rn levels near or below 150 Bq m-3, government programs should continue to focus on public information and consumer protection. For the small number of homes with high Rn levels, government programs should focus on identifying high risk homes and encouraging homeowners to reduce Rn levels. Because of the potential for substantial risk reduction, such efforts would be cost-effective in these homes. PMID- 1899234 TI - The lipase inhibitor tetrahydrolipstatin binds covalently to the putative active site serine of pancreatic lipase. AB - Tetrahydrolipstatin (THL) is a selective inhibitor of fat absorption. In animal models, it has anti-obesity and anti-hypercholesterolemic activity and is presently in clinical trials for these indications. THL binds covalently to pancreatic lipase. Complete inhibition of lipolytic activity is obtained concomitant with the incorporation of 1 mol of THL/mol of enzyme. Pancreatic lipase is the best studied lipase, but published results concerning its catalytic mechanism are still controversial. In order to learn more about the inhibitory mechanism of THL, a selective lipase inhibitor interacting at or near the catalytic site, and therefore, to obtain more information on the catalytic mechanism of lipase, we have determined the amino acid residue to which THL is bound. After proteolytic degradation of porcine pancreatic lipase inhibited with radioactively labeled THL, the labeled peptides were isolated and analyzed by quantitative amino acid analysis, N-terminal sequencing, and by mass spectrometry with fast atom bombardment ionization. The data clearly show that THL is bound as an ester to the serine 152 of the lipase. PMID- 1899235 TI - Mechanism of stimulation of DNA replication by bacteriophage phi 29 single stranded DNA-binding protein p5. AB - Protein p5 is a Bacillus subtilis phage phi 29-encoded protein required for phi 29 DNA replication in vivo. Protein p5 has single-stranded DNA binding (SSB) capacity and stimulates in vitro DNA replication severalfold when phi 29 DNA polymerase is used to replicate either the natural phi 29 DNA template or primed M13 single-stranded DNA (ssDNA). Furthermore, other SSB proteins, including Escherichia coli SSB, T4 gp32, adenovirus DNA-binding protein, and human replication factor A, can functionally substitute for protein p5. The stimulatory effect of phi 29 protein p5 is not due to an increase of the DNA replication rate. When both phi 29 DNA template and M13 competitor ssDNA are added simultaneously to the replication reaction, phi 29 DNA replication is strongly inhibited. This inhibition is fully overcome by adding protein p5, suggesting that protein p5-coated M13 ssDNA is no longer able to compete for replication factors, probably phi 29 DNA polymerase, which has a strong affinity for ssDNA. Electron microscopy demonstrates that protein p5 binds to M13 ssDNA forming saturated complexes with a smoothly contoured appearance and producing a 2-fold reduction of the DNA length. Protein p5 also binds to ssDNA in the phi 29 replicative intermediates produced in vitro, which are similar in structure to those observed in vivo. Our results strongly suggest that phi 29 protein p5 is the phi 29 SSB protein active during phi 29 DNA replication. PMID- 1899237 TI - Purification and characterization of nitrous oxide reductase from Pseudomonas aeruginosa strain P2. AB - Nitrous oxide reductase, which catalyzes the reduction of N2O to N2, was purified in a largely oxidized form from Pseudomonas aeruginosa strain P2 by a simple anaerobic procedure to yield an enzyme with a peptide purity of 95-98%. For the native (dimeric) enzyme, Mr = 120,000 and for the denatured subunit, Mr = 73,000. The enzyme contained four Cu atoms/subunit, was purple in color, and exhibited a broad absorption band at 550 nm with an extinction coefficient of about 11,000 M 1 x cm-1 referenced to the dimer. It was nearly inactive as prepared but could be activated by incubation with 2-(N-cyclohexylamino)ethane sulfonate buffer, pH 10, to specific activities as high as 27 mumol of N2O x min-1 x mg-1.Km for N2O and benzyl viologen radical cation was about 2 and 4 microM, respectively, both before and after enzyme activation. Activation increased the t1/2 for turnover dependent inactivation from about 30 s to 5-10 min. Reduction of the enzyme by dithionite was kinetically biphasic and resulted in the loss of the 550-nm band and ultimate appearance of a 670-nm band. Isoelectric focusing revealed five components with pI values from 5.2 to 5.7. The pI values did not change following activation. The copper CD spectrum of the enzyme as prepared was different from that for the activated enzyme, whereas those for the enzyme after exposure to air and the activated enzyme were similar. Because the activated enzyme is a mixture of activated and inactive species, the specific activity of the activated species must be substantially greater than the observed value. Molecular heterogeneity may also explain the decreased optical absorbance and CD amplitude that resulted from the activation process. The data overall reinforce the view that the absorption spectrum of nitrous oxide reductase is not a good predictor of absolute activity. PMID- 1899236 TI - Serine utilization as a precursor of phosphatidylserine and alkenyl-(plasmenyl)-, alkyl-, and acylethanolamine phosphoglycerides in cultured glioma cells. AB - In several tissues and cell lines, serine utilized for phosphatidylserine (PS) synthesis is an eventual precursor of the base moiety of ethanolamine phosphoglycerides (PE). We investigated the biosynthesis and decarboxylation of PS in cultured C6 glioma cells, with particular attention to 1-O-alk-1'-enyl-2 acyl-sn-glycero-3-phosphoethanolamine (plasmenylethanolamine) biosynthesis. Incorporation of [3H]serine into PS reached a maximum within 4-8 h, and label in nonplasmenylethanolamine phosphoglyceride (NP-PE) and plasmenylethanolamine was maximal by 12-24 h and 48 h, respectively. After 8 h, label in PS decreased even though 40-60% of initial label remained in the culture medium. Serial additions of fresh [3H]serine restored PS synthesis to higher levels of labeled PS accumulation followed by a subsequent decrease in 4-8 h. High performance liquid chromatographic analyses confirmed that medium serine was depleted by 8 h, and thereafter metabolites, including acetate and formate, accounted for radioactivity in the medium. The rapid but transient appearance of labeled glycine and ATP inside the cells indicated conversion of serine by hydroxymethyltransferase. 78-85% of label from serine was in headgroup of PS or of PE formed by decarboxylation. A precursor-product relationship was suggested for label from [3H]serine appearing in the headgroup of diacyl, alkylacyl, and alkenylacyl subclasses of PE. By 48 h, a constant specific activity, ratio of approximately 1:1 was reached between plasmenylethanolamine and NP-PE, similar to the molar distribution of these lipids. In contrast, equilibrium was not achieved in cells incubated with [1,2-14C]ethanolamine; plasmenylethanolamine had 2-fold greater specific activity than labeled NP-PE by 72-96 h. These observations indicate that in cultured glioma cells 1) serine serves as a precursor of the head group of PS and of both plasmenyl and non-plasmenyl species of PE; 2) exchange of headgroup between NP-PE and plasmenylethanolamine may involve different donor pools of PE depending on whether the headgroup originates with exogenous serine or ethanolamine; 3) serine is rapidly converted to other metabolites, which limits exogenous serine as a direct phospholipid precursor. PMID- 1899238 TI - Muscle glycogenolysis. Regulation of the cyclic interconversion of phosphorylase a and phosphorylase b. AB - Regulation of glycogenolysis in skeletal muscle is dependent on a network of interacting enzymes and effectors that determine the relative activity of the enzyme phosphorylase. That enzyme is activated by phosphorylase kinase and inactivated by protein phosphatase-1 in a cyclic process of covalent modification. We present evidence that the cyclic interconversion is subject to zero-order ultrasensitivity, and the effect is responsible for the "flash" activation of phosphorylase by Ca2+ in the presence of glycogen. The zero-order effect is observable either by varying the amounts of kinase and phosphatase or by modifying the ratio of their activities by a physiological effector, protein phosphatase inhibitor-2. The sensitivity of the system is enhanced in the presence of the phosphorylase limit dextrin of glycogen which lowers the Km of phosphorylase kinase for phosphorylase. The in vitro experimental results are examined in terms of physiological conditions in muscle, and it is shown that zero-order ultrasensitivity would be more pronounced under the highly compartmentalized conditions found in that tissue. The sensitivity of this system to effector changes is much greater than that found for allosteric enzymes. Furthermore, the sensitivity enhancement increases more rapidly than energy consumption (ATP) as the phosphorylase concentration increases. Energy effectiveness is shown to be a possible evolutionary factor in favor of the development of zero-order ultrasensitivity in compartmentalized systems. PMID- 1899239 TI - Identification of phosphorylation sites in the repetitive carboxyl-terminal domain of the mouse RNA polymerase II largest subunit. AB - The largest subunit of eukaryotic RNA polymerase II contains a carboxyl-terminal domain (CTD) which is comprised of repetitive heptapeptides with a consensus sequence Tyr1-Ser2-Pro3-Thr4-Ser5-Pro6-Ser7. We demonstrate here that the mouse CTD expressed in and purified from Escherichia coli can be phosphorylated in vitro by a p34cdc2/CDC28-containing CTD kinase from mouse ascites tumor cells. The product of this reaction, a phosphorylated form of the CTD, contains phosphoserine and phosphothreonine, but not phosphotyrosine. The same phosphoamino acid content is observed in the in vivo phosphorylated CTD from a mouse cell line. Synthetic peptides with naturally occurring non-consensus heptapeptide sequences can also be phosphorylated by CTD kinase in vitro. Phosphoamino acid analysis of these non-consensus heptapeptides together with direct sequencing of a phosphorylated heptapeptide reveals that serines (or threonines) at positions two and five are the sites phosphorylated by mouse CTD kinase. Thus, the -Ser(Thr)-Pro- motif common to p34cdc2/CDC28-containing protein kinases is the recognition site for mouse CTD kinase. PMID- 1899240 TI - Isolation and characterization of Pseudomonas aeruginosa exotoxin A binding glycoprotein from mouse LM cells. AB - A Pseudomonas aeruginosa exotoxin A (PE) binding glycoprotein was affinity purified from toxin sensitive mouse LM cells. The binding protein was solubilized with Triton X-100 or Nonidet P-40 and purified on a PE-Sepharose affinity column. Polyacrylamide gel electrophoresis yielded a single band with an estimated molecular mass of greater than 300,000 Da. N-Linked carbohydrate was present, accounting for approximately 10% of the total mass of the molecule. The purified protein specifically bound PE. Incubation of purified protein specifically bound PE. Incubation of purified PE binding protein with toxin reduced toxicity to LM cells. We speculate on the role of this toxin binding glycoprotein in the intoxication process. PMID- 1899241 TI - Immunological characterization of xenogenic anti-metatype antibodies. AB - High affinity murine anti-fluorescein monoclonal antibody (Mab) 4-4-20 (K alpha = 1.3 x 10(10) M-1; IgG2a; kappa), affinity labeled with fluorescein isothiocyanate (I), served as the immunogen to elicit a xenogenic (rabbit) polyclonal "anti metatype" reagent in a rabbit specific for the liganded state. The reagent did not bind Mab 4-4-20 in its nonliganded (idiotypic) conformation and demonstrated no reactivity with fluorescein ligand. Interaction of the anti-metatype reagent with liganded 4-4-20 caused a significant decrease in the dissociation rate of fluorescyl ligand bound to Mab 4-4-20 and a single-chain antibody derivative of 4 4-20. Additionally, most members of the 4-4-20 idiotype family displayed the same kinetic effect in the presence of anti-metatype. Members most closely related to Mab 4-4-20 (based on concentration in Mab required to inhibit the 4-4-20 idiotype/4-4-20 anti-idiotype interaction 50%) showed relatively greater decreases in the dissociation rate, establishing a quantitative correlation between idiotype and metatype. The immunologically distinct metatypic state is discussed in terms of conformational changes in or near the active site upon binding ligand, possibly involving two amino acid residues which "close off" the mouth of the antibody-active site upon binding fluorescein. PMID- 1899242 TI - Depolarization-induced changes in the muscarinic receptor in rat brain and heart are mediated by pertussis-toxin-sensitive G-proteins. AB - Muscarinic receptor properties in rat cortical and brain stem synaptoneurosomes and in heart myocytes were examined at resting potential and at depolarization. Depolarization induced the conversion of agonist-binding sites of the receptor from a high to a low affinity state, which could be reversed by a return to resting potential. No effect was observed on the affinity of the receptor for antagonists. Pertussis-toxin (PTX)-catalyzed ADP-ribosylation of all substrates in both synaptoneurosomal and myocyte membranes, when conducted at resting potential, prevented depolarization-induced conversion of the receptor affinity in these preparations. The target substrates were identified by [32P]ADP ribosylation of membranes prepared from brain stem synaptoneurosomes. Autoradiography revealed labeling of a 39-kDa protein band, which reacted mainly with antibodies to the alpha-subunit of Go-proteins. The possible involvement of G-proteins in depolarization-induced changes in the receptor activity was further investigated by examining the effect of membrane potential on the PTX-sensitive binding of di- and triphosphated guanine nucleotides to synaptoneurosomal membranes. Brain stem synaptoneurosomes were made permeable to guanine nucleotides ([3H]GTP, [3H]GDP, [3H]5'-guanylyl imidodiphosphate) by treatment with ATP. After the synaptoneurosomes had been loaded with labeled GTP/GDP, resealed, and then subjected to either resting potential of short depolarization, binding of [3H]GDP to the membranes of depolarized synaptoneurosomes was 4.0 +/- 0.3 (n = 20) times higher than to the membranes of synaptoneurosomes at resting potential. Repolarization reversed this effect. Enhancement of [3H]GDP binding to the synaptoneurosomal membranes was induced also by muscarinic activation, although the increase obtained was only 30-40% (n = 5) relative to [3H]GDP binding at resting potential. Both the depolarization-induced and the muscarinically-induced enhancement of [3H]GDP binding were prevented following PTX-catalyzed ADP-ribosylation of G-proteins in the synaptoneurosomal membrane. Our results suggest that the depolarization-induced enhancement in the binding of [3H]GTP/[3H]GDP may be attributable to activation of PTX-sensitive G-proteins, which mediate the depolarization-induced alteration of the affinity of the muscarinic receptor for agonists. PMID- 1899243 TI - Human ADP-ribosylation factors. A functionally conserved family of GTP-binding proteins. AB - A new member, hARF4, of the ADP-ribosylation factor (ARF) family, a subset of the superfamily of regulatory GTP-binding proteins, has been cloned from a cDNA expression library. Two other human ARF cDNA sequences, designated human ARF1 and ARF3, have been reported previously and are 96% identical in amino acid sequence. A human ARF1 cDNA, significantly longer than previously described clones, was obtained, by cross-species hybridization using a bovine ARF1 cDNA probe. Bovine ARF1p and human ARF1p are 100% identical while each is only 80% identical to hARF4p. Thus, hARF4p is the most divergent of the mammalian ARF proteins identified. Northern blot analysis revealed the expression of at least three different ARF messages in human placenta and adrenal carcinoma cells. Both hARF1 and hARF4 encode GTP-binding proteins with predicted molecular masses of 20,000 21,000 Da. Biochemical analysis of the purified recombinant proteins revealed a high degree of conservation of nucleotide binding properties and in vitro ARF activities. ARF is an essential gene in the yeast, Saccharomyces cerevisiae, and is encoded by two genes. Expression of either hARF1p or hARF4p in yeast was found to rescue the lethal double mutant, arf1-arf2-, thus demonstrating the functional conservation of ARF functions between yeast and man. The combination of in vivo and in vitro assays for ARF function provides a specific and unambiguous means of determining bona fide ARF proteins from divergent species from among the rapidly increasing number of structurally related, small molecular weight GTP-binding proteins. PMID- 1899244 TI - A family of ras-like GTP-binding proteins expressed in electromotor neurons. AB - The cDNAs encoding seven low molecular weight (LMW) GTP-binding proteins were isolated from an electrode lobe library of the marine ray Discopyge ommata. Four were assigned as the ray homologues of previously identified LMW GTP-binding proteins rab1, ral, Krev, and rho. Three others showed unique sequences, including two exhibiting significant similarity to the yeast SEC4 protein. Northern analysis indicated that several of the transcripts are enriched in neural tissues with a moderate level of expression in cardiac muscle. This tissue distribution was corroborated with affinity purified antibodies against the LMW GTP-binding proteins. Subcellular fractionation revealed that the proteins co purify with cholinergic synaptic vesicles. Immunohistochemical analysis confirms this localization. At least two of the proteins, oral and o-rho, are localized to the pre-synaptic terminals. PMID- 1899245 TI - Transforming growth factor beta 1 enhances expression of 50 kDa protein related to 2'-5' oligoadenylate synthetase in human sperm cells. AB - Human cellular polypeptide factors, namely interferon-alpha, interferon-gamma transforming growth factor (TGF)-alpha, and TGF-beta 1, were analyzed for their effect on motility of human sperm cells. Both interferons caused an inhibition of sperm cell motility due to direct cytotoxic effects without inducing 2'-5' oligoadenylate [2-5(A)]synthetase activity. TGF-alpha affected neither motility nor the levels of 2-5(A) synthetase in sperm cells. TGF-beta 1 had no affect on sperm motility, yet it caused an induction of 2-5(A)synthetase activity. Western immunoblot analysis of TGF-beta 1-treated sperm indicated an enhancement of a 50 kDa protein. Metabolic labeling of sperm cells revealed biosynthesis of one major protein of 50 kDa and at least five minor proteins in the range of 30-92 kDa; the level of 50 kDa protein increased after treatment with TGF-beta 1. The treatment of sperm cells with TGF-beta 1 did not affect their penetration in zona-free hamster eggs (SPA). These results indicate that TGF-beta 1 enhances expression of a 50 kDa protein related to 2-5(A) synthetase in human sperm cells along with other minor proteins, and this increase does not affect sperm motility and SPA. PMID- 1899246 TI - Two patients and one problem. PMID- 1899247 TI - Cardiac arrest in an on-call intern. PMID- 1899248 TI - On being an essayist. PMID- 1899249 TI - Asthma: the molecular light at the end of the tracheal tunnel. PMID- 1899250 TI - "And the Children". PMID- 1899251 TI - Asthma mortality--the need for a "WHAM-TF". PMID- 1899252 TI - Tachycardia three months after a heart attack. PMID- 1899253 TI - Diagnosis and the structure of memory. 3. The nature of categories. PMID- 1899254 TI - Systemic fungal infections: an overview. AB - Increasingly more common, these infections pose diagnostic and therapeutic problems. The distinction between primary infection in healthy hosts and opportunistic infection in the immunocompromised remains clinically useful. Three major diseases in each category are discussed. A promising therapeutic advance is the introduction of orally administered azoles. PMID- 1899255 TI - Hyperthyroidism in the geriatric population. AB - Although the thyroid gland can become overactive at any age, the syndrome of hyperthyroidism changes considerably in elderly persons. The principal reason is comorbidity. The patient over age 65 is much more likely than a young adult of 20 or 25 to have one or more preexisting disorders when the thyroid becomes overactive. In the elderly, therefore, the classic picture of hyperthyroidism- the constellation of irritability, sweating, palpitations without heart disease, weight loss despite good appetite, goiter, and warm, fine skin, familiar to all physicians--may never develop. Well before it might have appeared, a milder degree of thyroid hyperfunction may become manifest because of worsening of an underlying disease. Accordingly, the recognition of the thyroid disorder is often delayed. The purpose of this article is not so much to review hyperthyroidism as to delineate the special features found in geriatric patients and to describe a simple but effective scheme of evaluation. PMID- 1899256 TI - Alpha 1-antitrypsin deficiency: pathogenesis and treatment. AB - Inherited defects of the gene coding for a serum protein that protects alveolar walls from proteolysis constitute one cause of emphysema, with or without liver disease. The deficiency can be reversed with intravenous administration of the antiprotease, keeping serum levels above the minimum needed for lung protection. PMID- 1899257 TI - Follow-up and care of childhood cancer survivors. AB - More children than ever before are being cured of cancer, thanks to aggressive use of multimodal therapy. Of prime concern are the potential long-term deleterious effects of such treatment. Sequelae may include impairment of growth or other aspects of development, damage to various organ systems, or a second cancer. Guidelines for surveillance and counseling are described. PMID- 1899258 TI - Personal accounts of satisfying and unsatisfying nursing experiences as a needs assessment strategy. AB - This article describes the assessment process by which learning needs of a select group of nurses in a forensic psychiatric setting were identified and used for continuing education (CE) program planning. To determine whether a gap existed between what the nurses currently knew and what they needed to know in order to have a sense of accomplishment, their personal accounts of satisfying and unsatisfying nursing experiences were analyzed. The factors that influenced these experiences were categorized according to a theory of basic human needs, and learning needs were identified from those categories. Implications for the planning of content and methodology of CE programs for the study group were then developed. PMID- 1899259 TI - Management needs of head nurses and supervisors: designing a continuing education course. AB - Studies have confirmed the need for continuing education (CE) management courses for hospital nurse managers facing new challenges as decentralization has occurred. Increased problem-solving and decision-making skills are necessary as middle nurse managers attempt to manage more effectively in the current healthcare climate. Head nurses and supervisors may well have the most stressful positions in hospitals. A needs assessment of these individuals was conducted in order to design a management course to provide practical knowledge for contemporary nurse managers. PMID- 1899260 TI - Effective teacher characteristics identified by adult learners in nursing. AB - What characteristics should adult education nursing faculty use to get and maintain the attention and interest of learners? There is a dearth of research or literature available to guide nursing faculty in "grabbing" the learner's interest or attention. Thus, the outcome of this project identified 20 attributes as effective teacher characteristics perceived by learners. Further, these attributes were used to generate a checklist to enhance an educator's ability to hone in on salient characteristics desired by nursing continuing education learners. This checklist, "Be Prepared to Teach," will assist the educator to utilize both professional and personal characteristics perceived as effective by adult learners. PMID- 1899261 TI - Maintaining clinical excellence in a weekend alternative program: the role of the divisional clinical manager. AB - Many innovative management changes designed to promote clinical excellence and scholarship were undertaken by the nursing executive team at our 821-bed tertiary care teaching hospital. Included in these changes was the creation of the divisional clinical manager (DCM). The purpose of this article is to describe how these weekend managers employees contribute to the overall objectives of providing consistent supervision, clinical support and a rich continuing education program. PMID- 1899262 TI - Meeting the continuing education needs of nurses in rural settings. AB - Access to continuing education (CE) for rural nurses is hampered by distance, cost factors, and the lack of sufficient personnel to provide coverage when nurses are away from work. Additionally, because rural nurses function as generalists rather than specialists, CE programs should focus on the generalist perspective. The Nevada Area Health Education Center (AHEC) has developed a partnership model for providing CE that addresses these considerations, bringing educational programs to the rural site eliminates travel, cost, and coverage problems for the hospitals. In turn, a close working relationship between AHEC and rural personnel to assess needs and coordinate the planning is critical. Attention to logistical detail is critical. The partnership model described is the foundation of a year-round CE program for nurses working in rural and frontier areas. PMID- 1899263 TI - State and association continuing education requirements. PMID- 1899264 TI - Brief: medical nursing grand rounds: learning, sharing, caring. PMID- 1899266 TI - The 10-minute learning break. PMID- 1899265 TI - Brief: successful strategies for a reentry program--one example. PMID- 1899268 TI - The Gastro-port: an alternative to the Button. PMID- 1899267 TI - Empowering nurses for politically astute change in the workplace. AB - While studies of the shortage of nurses have documented the need for nurses to play a greater role in decision-making processes in their workplaces, it cannot be assumed that nurses have the confidence or skills for making changes in the workplace in politically astute ways that will be effective. This article describes a continuing education program that was designed to prepare nurses to realize their potential power and to develop skills for effectively bringing about changes in their workplaces. Based on a feminist model of empowerment, the program content and methods reflected three dimensions of empowerment: consciousness-raising, building self-esteem, and skill development. Both short- and long-term evaluations (immediate and at 7 months) demonstrated that education can be a vehicle for empowering nurses to effectively bring about changes in their workplaces. The program was sponsored by the Manitoba Nurses Union, The University of Manitoba Continuing Education Division, and The University of Manitoba School of Nursing. PMID- 1899269 TI - Effects of lamellolysin from a parasitoid wasp on Drosophila blood cells in vitro. AB - Female parasitoid Leptopilina heterotoma inject a factor, lamellolysin, along with their eggs into the host hemocoel to destroy selectively host hemocytes that encapsulate foreign objects. In parasitized Drosophila melanogaster larvae, these hemocytes (lamellocytes) change from discoidal cells to bipolar cells that no longer adhere to each other to form capsules. To study the effects of lamellolysin on Drosophila lamellocytes in vitro, a giant strain of D. melanogaster was constructed to yield hemolymph with an abundance of lamellocytes. The effect of lamellolysin on the adhesivity of lamellocytes in vitro was demonstrated when the cells were gently rotated in the culture medium. Under these conditions, the bipolar shape of the affected lamellocytes resembled that of lamellocytes in parasitized hosts. When lamellocytes were exposed to lamellolysin in stationary culture medium, the elongation of the bipolar cells continued until they became threadlike. Lamellocytes fragmented in both stationary and rotating culture medium in the presence of lamellolysin, although loss of cellular material was more pronounced in the latter. This study demonstrates that lamellolysin acts directly and destructively on lamellocytes. PMID- 1899271 TI - Pathogenicity of Listeria monocytogenes isolates in immunocompromised mice in relation to listeriolysin production. AB - The virulence of 74 Listeria monocytogenes isolates from clinical cases and food products and of 11 isolates of other Listeria species was tested in mice immunocompromised with carrageenan. Isolates of species other than L. monocytogenes were not lethal to such mice. All 29 clinical isolates of L. monocytogenes (serotypes 1/2a, 1/2b, 4b) and 33 of 42 isolates of various serotypes isolated mainly from dairy products killed all test mice (100% lethality) at an inoculum of 10(4) cfu/mouse. All lethal strains of L. monocytogenes were haemolytic and possessed the 58-Kda band specific for listeriolysin O as demonstrated by SDS-PAGE immunoblotting. The nine avirulent strains of L. monocytogenes had detectable haemolytic activity, but in six of them this activity was significantly weaker than in virulent strains and the 58 Kda band was not detected. The other three avirulent strains were highly haemolytic and possessed the 58-Kda band, which suggests that other factor(s) could be involved in the virulence of L. monocytogenes. PMID- 1899270 TI - Search for a putative scrapie genome in purified prion fractions reveals a paucity of nucleic acids. AB - Scrapie can be transmitted by novel infectious pathogens termed prions. No evidence for a scrapie-specific nucleic acid has been detected to date. To investigate amounts, types and sizes of nucleic acid molecules associated with prions in purified preparations, aliquots were deproteinized, and the nucleic acids analysed by PAGE and silver staining. Digestion with nucleases and exposure to Zn2+ prior to analysis substantially diminished the content of nucleic acids, but did not alter the prion titre indicating that those nucleic acids which were removed are not essential for infectivity. Since a single species of scrapie specific nucleic acid could not be identified, we explored the unprecedented possibility of scrapie-specific nucleic acids of variable length which are biologically active. If such molecules of variable length exist then they might be hidden within the background smear on silver-stained gels after PAGE. A new procedure designated return refocusing gel electrophoresis (RRGE) was developed to identify heterogeneous nucleic acids in purified prion fractions. The content of variable length nucleic acids was reduced by a factor of 10 by exhaustive Bal 31 exonuclease digestion after dispersion of purified prions into detergent-lipid protein complexes. For example, a typical sample after Bal 31 digestion contained approximately 4 ng of nucleic acid of variable length and 10(8.7) ID50 units of scrapie prion infectivity. Consideration of different models for a hypothetical scrapie-specific nucleic acid suggests that such a molecule would have to be: (i) quite small (less than 100 nucleotides), (ii) possess a particle-to-infectivity ratio near unity or (iii) heterogeneous in size. Although our results do not eliminate the possibility that prions possess a scrapie-specific nucleic acid of variable length, they narrow considerably the spectrum of features specifying such a candidate molecule. PMID- 1899272 TI - 4-Quinolone-resistant Neisseria gonorrhoeae in the United Kingdom. AB - The auxotype, serogroup and antimicrobial susceptibility of 977 clinical isolates of Neisseria gonorrhoeae obtained at St Thomas' Hospital, London, during 1989 were determined; 23 isolates from 15 patients were resistant to 4-quinolones. Twelve of the patients acquired their infection in the UK and these strains were generally sensitive to other antimicrobial agents; strains from 10 patients were of serogroup IB-6. Three patients acquired their strains outside the UK and these isolates were multi-resistant and of different serogroups. PMID- 1899273 TI - Kinetics of adherence of mucoid and non-mucoid Pseudomonas aeruginosa to plastic catheters. AB - The adherence of six non-mucoid and three mucoid strains of Pseudomonas aeruginosa to polyvinyl chloride (PVC), polyurethane (PU) and siliconised latex (SL) was evaluated by a radiometric method and scanning electronmicroscopy. Initially greater numbers of mucoid than non-mucoid strains adhered to all three materials. Hydrophobic non-mucoid strains adhered more efficiently than hydrophilic strains. Numbers of adherent non-mucoid P. aeruginosa cells increased with time, reaching a peak, which was different for each strain, at 1-4 h for PU, 4 h-2 days for SL and 2-3 days for PVC; thereafter a gradual decrease was observed, maximal and final values of adherence being higher with PVC and SL than with PU. Adherence of mucoid strains increased with time in 3-5 days, until a steady state was reached. We conclude that although non-mucoid strains of P. aeruginosa initially colonise plastic surfaces better than mucoid strains, mucoid strains also persist on these surfaces. PMID- 1899275 TI - Fatal Rocky Mountain spotted fever in Maryland--1901. PMID- 1899274 TI - Clinical applications of carbon dioxide/digital subtraction arteriography. AB - During an 18-month period 33 patients in whom there were contraindications to the use of iodinated contrast arteriography underwent 40 carbon dioxide/digital subtraction arteriograms for lower extremity ischemia (19), severe hypertension and renal insufficiency (12), or arterial aneurysm (2). Contraindications to iodinated contrast agents included renal insufficiency, congestive heart failure, and contrast hypersensitivity. Sixteen aortic, 15 iliac-femoral-popliteal-tibial, five aorta-iliac-femoral and four aorta-iliac-femoral-popliteal-tibial carbon dioxide/digital subtraction arteriography studies were performed. In 11 studies, imaging of selected arterial segments required the addition of 10 to 60 ml of dilute nonionic contrast. Guided by carbon dioxide/digital subtraction arteriography studies four femoral-tibial bypasses, three aneurysmorrhaphies, two aortorenal bypasses, one aortofemoral bypass and one femoral-femoral bypass were successfully performed in 11 patients. In addition, carbon dioxide/digital subtraction arteriography directed angioplasties of the common iliac (4), superficial femoral (6), popliteal (3), or tibioperoneal trunk (1) were performed in 10 patients. Complications of carbon dioxide/digital subtraction arteriography included transient deterioration in renal function in three patients in whom 20 ml of nonionic contrast was used, a nonfatal myocardial infarction after a popliteal percutaneous transluminal angioplasty in one patient, and transient tachypnea and tachycardia during a carbon dioxide/digital subtraction arteriography study in one patient. Diagnostic arteriograms are obtainable using carbon dioxide as the contrast agent. Carbon dioxide/digital subtraction arteriography permits patients with symptomatic arterial disease at high risk for contrast related complications to safely undergo arteriography and subsequent arterial reconstruction or endovascular intervention. PMID- 1899276 TI - Current treatment of patients surviving out-of-hospital cardiac arrest. AB - Most out-of-hospital cardiac arrests result from the sudden onset of a sustained ventricular arrhythmia in the absence of a new myocardial infarction. Individuals who survive cardiac arrest are at high risk for recurrent arrhythmias and sudden unexpected death. To prevent recurrent cardiac arrest, effective treatment must be provided during hospitalization after the initial episode. Caring for the survivor of cardiac arrest requires a detailed clinical investigation to define the underlying cardiac anatomy and left ventricular function and to elucidate the mechanism and characteristics of the patient's arrhythmia. Appropriate antiarrhythmic therapy, such as drugs or a nonpharmacological intervention (eg, implantable cardioverter-defibrillator), is then selected based on these considerations. In addition, ischemia is treated aggressively with beta adrenergic blocking agents and, when appropriate, with surgical coronary artery revascularization. PMID- 1899277 TI - What care is 'essential'? What services are 'basic'? PMID- 1899278 TI - Alterations in thyroid hormones, cortisol, and catecholamine concentration in patients after orthopedic surgery. AB - Changes in serum and plasma concentrations of thyroid hormones, cortisol, and catecholamines were measured simultaneously in 16 patients undergoing major elective orthopedic surgery. Blood samples were collected preoperatively and at 2, 6, 24, 48, 96, and 168 hr after surgery. A significant decrease in TT3 and FT3 and an increase in rT3 were noted after surgery. TT4 started to decrease 48 hr after surgery whereas FT4 showed no significant change over the same period of time. The concentration of TSH fell progressively after surgery reaching a nadir by Day 7. The concentrations of cortisol were increased markedly throughout the course after surgery. Adrenaline and noradrenaline levels were increased markedly during the first 24 hr postsurgery. Both the thyroglobulin and TBG together with albumin concentration values were decreased after surgery as compared to preoperative values. It is concluded that the changes in thyroid hormone levels after major elective orthopedic surgery seem to be independent of changes in plasma catecholamines and/or cortisol concentrations. PMID- 1899279 TI - Dual effect of osmotic cell swelling on prolactin secretion by acutely dispersed adenohypophyseal cells. AB - Cell swelling induced by acute exposure to the permeant molecule urea or by medium hyposmolarity evoked a prompt PRL secretory burst from dispersed rat anterior pituitary cells. However, during continuous exposure greater than or equal to 10 min to these conditions inhibition of basal and TRH-induced PRL secretion occurred and there was an "off" burst of PRL secretion following return to basal conditions. Compared with continuous TRH stimulation which causes biphasic PRL secretion with a rapid high amplitude first phase secretory burst followed by a sustained low level second phase of secretion, cell swelling induced only "first phase" secretion. Removing Ca2+ from the medium or adding 50 microM verapamil markedly depressed the "off" secretory burst following return to basal conditions but had no effect on the initial high amplitude burst. Our data suggest that the effect of cell swelling on PRL secretion is complex and that there are at least two mechanisms for PRL secretion in normal anterior pituitary cells; these are differently affected by cell swelling and Ca2+ influx. PMID- 1899280 TI - Haemophilus b conjugate vaccines for prevention of Haemophilus influenzae type b disease among infants and children two months of age and older. Recommendations of the immunization practices advisory committee (ACIP). AB - These recommendations include information on use of two vaccines recently licensed for use with infants: Haemophilus b Conjugate Vaccine (Diphtheria CRM197 Protein Conjugate) (HbOC), manufactured by Praxis Biologics, Inc., and Haemophilus b Conjugate Vaccine (Meningococcal Protein Conjugate) (PRP-OMP), manufactured by Merck Sharp and Dohme, newly licensed for use with infants. This statement also updates recommendations for use of these and other Haemophilus b conjugate vaccines with older children and adults. PMID- 1899281 TI - Functional characterization of the developmentally controlled immunoglobulin kappa 3' enhancer: regulation by Id, a repressor of helix-loop-helix transcription factors. AB - We have functionally characterized an enhancer element (kappa E3') which lies 8.5 kb downstream of the immunoglobulin kappa gene. The activity of this enhancer is developmentally controlled. It is inactive at the pre-B-cell stage but active at the B-cell and plasma cell stages. This enhancer is also functional in S107 plasmacytoma cells, which lack NF-kappa B and therefore intron enhancer activity. The activity of the kappa E3' enhancer therefore provides an explanation for the transcriptional activity of endogenous kappa genes in S107 cells in the absence of intron enhancer function. We have identified a 132-bp segment of the kappa E3' enhancer that retains 75% of the activity of the entire enhancer observed in plasmacytoma cells. Within this 132-bp core, there are at least two functional elements, one of which binds to a B-cell-specific nuclear factor. This element contains a potential binding site for the B-cell- and macrophage-specific transcription factor PU.1. The kappa intron and kappa E3' enhancers were also found to be regulatable by Id, an inhibitor of helix-loop-helix transcription factors. The site of action of Id on the kappa E3' enhancer was mapped to a 25-bp region which contains a potential binding site for a helix-loop-helix transcription factor. A possible model for the developmental control of kappa gene transcription is discussed. PMID- 1899282 TI - Heat shock proteins affect RNA processing during the heat shock response of Saccharomyces cerevisiae. AB - In the yeast Saccharomyces cerevisiae, the splicing of mRNA precursors is disrupted by a severe heat shock. Mild heat treatments prior to severe heat shock protect splicing from disruption, as was previously reported for Drosophila melanogaster. In contrast to D. melanogaster, protein synthesis during the pretreatment is not required to protect splicing in yeast cells. However, protein synthesis is required for the rapid recovery of splicing once it has been disrupted by a sudden severe heat shock. Mutations in two classes of yeast hsp genes affect the pattern of RNA splicing during the heat shock response. First, certain hsp70 mutants, which overproduce other heat shock proteins at normal temperatures, show constitutive protection of splicing at high temperatures and do not require pretreatment. Second, in hsp104 mutants, the recovery of RNA splicing after a severe heat shock is delayed compared with wild-type cells. These results indicate a greater degree of specialization in the protective functions of hsps than has previously been suspected. Some of the proteins (e.g., members of the hsp70 and hsp82 gene families) help to maintain normal cellular processes at higher temperatures. The particular function of hsp104, at least in splicing, is to facilitate recovery of the process once it has been disrupted. PMID- 1899285 TI - Expression of bovine superoxide dismutase in Drosophila melanogaster augments resistance of oxidative stress. AB - Superoxide dismutases (SOD) play a major role in the intracellular defense against oxygen radical damage to aerobic cells. In eucaryotes, the cytoplasmic form of the enzyme is a 32-kDa dimer containing two copper and two zinc atoms (CuZn SOD) that catalyzes the dismutation of the superoxide anion (O2-) to H2O2 and O2. Superoxide-mediated damage has been implicated in a number of biological processes, including aging and cancer; however, it is not certain whether endogenously elevated levels of SOD will reduce the pathological events resulting from such damage. To understand the in vivo relationship between an efficient dismutation of O2- and oxidative injury to biological structures, we generated transgenic strains of Drosophila melanogaster overproducing CuZn SOD. This was achieved by microinjecting Drosophila embryos with P-elements containing bovine CuZn SOD cDNA under the control of the Drosophila actin 5c gene promoter. Adult flies of the resulting transformed lines which expressed both mammalian and Drosophila CuZn SOD were then used as a novel model for evaluating the role of oxygen radicals in aging. Our data show that expression of enzymatically active bovine SOD in Drosophila flies confers resistance to paraquat, an O2(-) generating compound. This is consistent with data on adult mortality, because there was a slight but significant increase in the mean lifespan of several of the transgenic lines. The highest level of expression of the active enzyme in adults was 1.60 times the normal value. Higher levels may have led to the formation of toxic levels of H2O2 during development, since flies that died during the process of eclosion showed an unusual accumulation of lipofuscin (age pigment) in some of their cells. In conclusion, our data show that free-radical detoxification has a minor by positive effect on mean longevity for several strains. PMID- 1899283 TI - Different forms of Go alpha mRNA arise by alternative splicing of transcripts from a single gene on human chromosome 16. AB - Go alpha, (gene symbol GNA01), a member of the signal-transducing guanine nucleotide-binding (G) protein family, has been implicated in ion channel regulation. Some tissues contain multiple Go alpha mRNAs of different sizes that differ in the 3' untranslated regions (UTRs). Using sequence-specific 48-base oligonucleotides, two complementary to the different 3' UTRs and one complementary to the coding region, we investigated the origin of the multiple Go alpha transcripts, the organization of the Go alpha gene, the interspecies conservation of 3' UTRs, and the chromosomal localization of Go alpha. Oligonucleotides labeled to high specific activity by using terminal deoxynucleotidyltransferase each hybridized with a single band of restriction enzyme-digested mouse and human DNAs. In three of four digests of human DNA, the two probes specific for the different 3' UTRs hybridized with the same restriction fragment. Thus, these nucleotide sequences are in close proximity in the human genome. The order of the UTRs in the bovine, human, and mouse genomes was confirmed directly by polymerase chain reaction (PCR) amplification and sequencing. Hybridization of bovine oligonucleotide sequence with mouse and human genomic DNA indicated a high degree of interspecies sequence conservation: conservation was confirmed by PCR amplification and sequencing. Bands detected by both UTR probes, as well as the predominant bands detected by a bovine Go alpha cDNA, segregated with human chromosome 16 on Southern blot analysis of human mouse somatic cell hybrids. We conclude that Go alpha mRNAs with different 3' UTRs arise by alternative splicing of transcripts from a single gene. The UTRs, which exhibit a high degree of interspecies conservation, may play a role in regulation of Go alpha expression during differentiation or in specific tissues. The use of oligonucleotide probes of the type described here represents a new strategy, potentially widely applicable for mapping and elucidating structural features of genes. PMID- 1899284 TI - The Schizosaccharomyces pombe homolog of Saccharomyces cerevisiae HAP2 reveals selective and stringent conservation of the small essential core protein domain. AB - The fission yeast Schizosaccharomyces pombe is immensely diverged from budding yeast (Saccharomyces cerevisiae) on an evolutionary time scale. We have used a fission yeast library to clone a homolog of S. cerevisiae HAP2, which along with HAP3 and HAP4 forms a transcriptional activation complex that binds to the CCAAT box. The S. pombe homolog php2 (S. pombe HAP2) was obtained by functional complementation in an S. cerevisiae hap2 mutant and retains the ability to associate with HAP3 and HAP4. We have previously demonstrated that the HAP2 subunit of the CCAAT-binding transcriptional activation complex from S. cerevisiae contains a 65-amino-acid "essential core" structure that is divisible into subunit association and DNA recognition domains. Here we show that Php2 contains a 60-amino-acid block that is 82% identical to this core. The remainder of the 334-amino-acid protein is completely without homology to HAP2. The function of php2 in S. pombe was investigated by disrupting the gene. Strikingly, like HAP2 in S. cerevisiae, the S. pombe gene is specifically involved in mitochondrial function. This contrasts to the situation in mammals, in which the homologous CCAAT-binding complex is a global transcriptional activator. PMID- 1899286 TI - The Saccharomyces cerevisiae ADR1 gene is a positive regulator of transcription of genes encoding peroxisomal proteins. AB - Expression of the CTA1 gene of Saccharomyces cerevisiae, encoding catalase A, the peroxisomal catalase of this yeast, is sensitive to glucose repression. A DNA fragment cloned as a multicopy plasmid suppressing the glucose repression of CTA1 transcription was demonstrated to contain the ADR1 gene. Multiple copies of ADR1 increased catalase A formation not only on 10% glucose, but also on ethanol medium and in the presence of oleic acid, an inducer of peroxisome proliferation. Compared with wild-type cells, adr1 null mutants produced by disruption of the gene exhibit reduced CTA1 expression. This demonstrates that ADR1 is a true positive regulator of CTA1. Further experiments showed that it acts directly on CTA1. Alcohol dehydrogenase II, which is under ADR1 control, was excluded as a mediator of the effect on CTA1; deletion of bases -123 to -168 of CTA1 reduces expression and eliminates the response to the ADR1 multicopy plasmid without eliminating fatty acid induction; and gel retardation experiments demonstrated that ADR1 binds to a CTA1 upstream fragment (-156 to -184) with limited similarity to the ADR1 binding site of ADH2. Northern hybridization experiments further demonstrated that expression of two genes encoding enzymes of peroxisomal beta-oxidation (beta-ketothiolase, trifunctional enzyme) and of a gene involved in peroxisome assembly (PAS1) is also negatively affected by the adr1 null mutation. These findings demonstrate that the ADR1 protein has much broader regulatory functions than previously recognized. PMID- 1899287 TI - Structure and expression of a gene encoding a putative GTP-binding protein identified by provirus integration in a transgenic mouse strain. AB - The Mov-10 mouse strain was derived by infection of preimplantation embryos with the Moloney murine leukemia virus and carries one copy of the provirus in its germ line. Here we show that the provirus has integrated into an evolutionarily conserved gene that can code for a protein of 110 kDa containing the three consensus elements characteristic for GTP-binding proteins. The Mov-10 locus was expressed in a variety of cell types, including embryonal carcinoma and embryonic stem cells. Transcription of the gene was down-regulated about 10-fold when F9 embryonal carcinoma cells are differentiated into parietal endodermlike cells and about 2-fold when they are differentiated into visceral endodermlike cells. High levels of Mov-10 transcripts were also found at different stages of embryonal development and in the testes and thymus of adult animals. Expression was cell cycle controlled, with steady-state RNA levels significantly higher in growth arrested than in growth-stimulated cells. The results suggest that the Mov-10 locus has an important function in development and/or control of cell proliferation. The provirus was shown to have integrated into intron 1 of the gene without disrupting expression, indicating that integration into intronic sequences of a transcription unit does not necessarily affect transcription. This result together with previous results from the Mov-13 mouse strain suggested that proviruses exert their mutagenic effect only by integration in specific sites, such as cis-regulatory DNA elements. PMID- 1899288 TI - The gene encoding the oligodendrocyte-myelin glycoprotein is embedded within the neurofibromatosis type 1 gene. AB - In the course of efforts to identify the neurofibromatosis type 1 gene (NF1), three genes were found embedded within an intron of NF1. The cDNA sequence of one of these genes (OMGP) encodes oligodendrocyte-myelin glycoprotein. OMGP spans at least 2.7 kb of genomic DNA, and it maps within 4 kb of the breakpoint of a balanced chromosomal translocation carried by an individual with NF1. OMGP is similar in genomic structure to two other expressed genes, EVI2A and EVI2B, which lie approximately 20 and 5 kb telomeric of the OMGP locus, respectively. All three genes have the same transcriptional orientation and are contained within one intron of NF1, which is transcribed off the opposite strand. Whether altered expression of OMGP might play a role in the clinical heterogeneity of NF1 is as yet unclear. PMID- 1899290 TI - [Costs and benefits of vaccination against Haemophilus influenzae type b]. AB - In the Netherlands, Haemophilus influenzae type b (Hib) causes invasive disease in hundreds of children every year; meningitis is the most frequent and most severe infection. Children from the age of 6 months can be protected against Hib diseases by conjugated vaccines. The financial consequences of the introduction of such vaccine into the state vaccination programme are considered in a cost effectiveness analysis. Some elements in the analysis are still uncertain, such as the price and the schedule and method of administration of the vaccine. Presumably, the costs and benefits will be in balance, if one vaccine dose will cost about 7 US $+ and if the administration can be combined with the present programme of vaccinations against diphtheria, whooping cough, poliomyelitis and tetanus. PMID- 1899291 TI - Detection of human factor B biosynthesis in culture supernatants and cell lysates by ELISA. AB - We report here on the development of a simple, sensitive, convenient, and quantitative enzyme-linked immunosorbent assay for human factor B, a protein of the alternative complement pathway, by the sandwich method using goat anti-human factor B antibody. The assay described herein is reproducible and highly specific for human factor B. The assay was used to determine biosynthesis (cell lysates or extracts) and secretion (supernatants) of human factor B using human monocyte cell line U937. Phorbol myristate acetate strongly enhanced (10- to 20-fold) biosynthesis of factor B by U937. The combination of a sensitive enzyme-linked immunosorbent assay and phorbol myristate acetate enabled us to use a microculture system. PMID- 1899289 TI - Spk1, a new kinase from Saccharomyces cerevisiae, phosphorylates proteins on serine, threonine, and tyrosine. AB - A Saccharomyces cerevisiae lambda gt11 library was screened with antiphosphotyrosine antibodies in an attempt to identify a gene encoding a tyrosine kinase. A subclone derived from one positive phage was sequenced and found to contain an 821-amino-acid open reading frame that encodes a protein with homology to protein kinases. We tested the activity of the putative kinase by constructing a vector encoding a glutathione-S-transferase fusion protein containing most of the predicted polypeptide. The fusion protein phosphorylated endogenous substrates and enolase primarily on serine and threonine. The gene was designated SPK1 for serine-protein kinase. Expression of the Spk1 fusion protein in bacteria stimulated serine, threonine, and tyrosine phosphorylation of bacterial proteins. These results, combined with the antiphosphotyrosine immunoreactivity induced by the kinase, indicate that Spk1 is capable of phosphorylating tyrosine as well as phosphorylating serine and threonine. In in vitro assays, the fusion protein kinase phosphorylated the synthetic substrate poly(Glu/Tyr) on tyrosine, but the activity was weak compared with serine and threonine phosphorylation of other substrates. To determine if other serine/threonine kinases would phosphorylate poly(Glu/Tyr), we tested calcium/calmodulin-dependent protein kinase II and the catalytic subunit of cyclic AMP-dependent protein kinase. The two kinases had similar tyrosine phosphorylating activities. These results establish that the functional difference between serine/threonine- and tyrosine-protein kinases is not absolute and suggest that there may be physiological circumstances in which tyrosine phosphorylation is mediated by serine/threonine kinases. PMID- 1899292 TI - [Severe endocrine ophthalmopathy. A review with case reports]. AB - The autoimmune pathogenesis of endocrine ophthalmopathy (EO) is only partly elucidated. About 40% of all patients with Graves' disease have clinically overt ophthalmopathy. 5% of all Graves' disease patients develop severe EO, independently of the treatment modality for thyrotoxicosis (radioiodine, surgery, antithyroid drugs) and require multidisciplinary treatment. In cases where glucocorticoid treatment is unsuccessful, orbital decompression, as described by Walsh and Ogura, should be considered. PMID- 1899293 TI - Regulation of the apolipoprotein AI gene by ARP-1, a novel member of the steroid receptor superfamily. AB - Apolipoprotein AI (apoAI) is a lipid-binding protein that participates in the transport of cholesterol and other lipids in the plasma. A complementary DNA clone for a protein that bound to regulatory elements of the apoAI gene was isolated. This protein, designated apoAI regulatory protein-1 (ARP-1), is a novel member of the steroid hormone receptor superfamily. ARP-1 bound to DNA as a dimer, and its dimerization domain was localized to the COOH-terminal region. ARP 1 also bound to a thyroid hormone-responsive element and to regulatory regions of the apoB, apoCIII, insulin, and ovalbumin genes. In cotransfection experiments, ARP-1 downregulated the apoAI gene. The involvement of ARP-1 in the regulation of apoAI gene expression suggests that it may participate in lipid metabolism and cholesterol homeostasis. PMID- 1899294 TI - Bupropion: overview and prescribing guidelines in depression. AB - Bupropion is a new antidepressant medicine that is chemically distinct from previous agents. Clinical studies have shown it to be as effective as the standard antidepressant drugs currently used in the treatment of major depression. It is useful in patients resistant to other agents as well as in patients with atypical depression. Bupropion is 10 to 100 times less likely to induce cardiac conduction problems than the tricyclic drugs, and orthostatic hypotension is rare. Minimal anticholinergic effects account for its being generally well tolerated. The most common side effect is dry mouth. An epileptogenic potential is prominently reported. Because it may lower the convulsive threshold, bupropion is not recommended for individuals who may be predisposed to seizures. In people without an increased ictal risk factor, and when dosage is maintained at 450 mg/day or less in a divided schedule, the seizure rate is comparable to that of other antidepressant drugs. PMID- 1899295 TI - Continuous intravenous infusion of morphine for severe dyspnea. AB - We describe eight patients who had terminal lung cancer causing severe dyspnea unrelieved by oxygen, nonnarcotic drugs, or intermittent bolus narcotics. We treated these patients with continuous intravenous infusion of morphine, beginning with bolus IV injections of 1 or 2 mg of morphine every 5 to 10 minutes until the patient reported relief. A continuous morphine infusion was then started, with the hourly dose equal to 50% of the cumulative bolus dose. Vital signs, degree of sedation, and blood gases were serially followed. Six patients achieved good dyspnea relief, one had moderate relief, and one had a poor response. Variable changes were noted in the PaO2, whereas PaCO2 steadily increased in five of seven patients, and pH decreased in six. There was little change in systolic blood pressure or pulse, and only one individual had less than 10 respirations per minute. The major side effect of treatment was sedation, treated by temporarily discontinuing morphine until the patients' mental status improved and then restarting the infusion at a 50% lower hourly morphine dose. Mean time of study was 30 hours (range 16 to 87 hours). Seven of the eight study patients died during treatment. Whether morphine therapy shortened survival is uncertain. We conclude that continuous morphine infusion is effective therapy for severe dyspnea. The treatment is ethically justified. Relief of suffering is the primary goal of therapy, and less risky treatments are unavailable. PMID- 1899296 TI - Pregnancy complicated by antiphospholipid antibodies. AB - The manifestations of antiphospholipid antibodies in pregnancy are multiple and include maternal arterial and venous thrombosis, spontaneous abortion, intrauterine fetal death, intrauterine growth retardation, and preeclampsia. Maternal complications may also arise in the puerperium with the development of an autoimmune pleuropulmonary postpartum syndrome. Currently, there is confusion in the literature regarding appropriate treatment of patients known to possess these antibodies. We have reported the case of a patient at 29 weeks' gestation who had elevated blood pressure, proteinuria, and early intrauterine growth retardation. Studies were positive for the presence of both lupus anticoagulant and anticardiolipin antibodies. After delivery, chest pain and a pleural effusion developed as further manifestations of the patient's autoimmune disease. PMID- 1899297 TI - Ampicillin remains inadequate therapy for enterococcal endocarditis. PMID- 1899298 TI - Immunogenicity of class I+, class II- hepatocytes. PMID- 1899299 TI - The role of CD8-mediated signals in the generation of MHC-restricted cytotoxic T lymphocyte effector cells. PMID- 1899300 TI - Mechanism of immunosuppressive action of the amniotic fluid on lymphocyte activation. PMID- 1899302 TI - Differential in situ expression of cytokine genes in human renal rejection. PMID- 1899301 TI - Levels of purine nucleoside phosphorylase (PNP) as a viability marker of nonparenchymal cells in cold preserved livers. PMID- 1899303 TI - The use of polymerase chain reaction (PCR) for assessing interferon-gamma (INF gamma) mRNA levels in human lymphocytes. PMID- 1899304 TI - The role of CD4+ and CD8+ T cells in rejection of class I MHC disparate renal allografts. PMID- 1899305 TI - Selective T-cell depletion of recipients in allogeneic small bowel transplantation (SBT) in the rat. PMID- 1899306 TI - Isolation of anti-OKT3 and anti-(anti-OKT3) from a kidney transplant recipient. PMID- 1899308 TI - Alteration of mouse T-cell receptor repertoire by Aa/DQb hybrid molecules in human HLA-DQb single transgenic mice. PMID- 1899307 TI - Cyclosporine inhibition of adherence proteins and factor VIII of vascular endothelium. PMID- 1899309 TI - Differential inducibility of HLA class I and II antigens by r-IFN gamma in type III bare lymphocyte syndrome. PMID- 1899310 TI - Posttransplant TLI is effective in nonhuman primates if combined with rabbit ATG. PMID- 1899311 TI - Deletion of graft reactive cells by idarubicin-anti-CD8 (Ly-2.1) immunoconjugate: studies in the mouse heart graft model. PMID- 1899312 TI - Cyclooxygenase blockade abrogates the prolonged survival resulting from drainage of rat cardiac allografts into the portal vein. PMID- 1899313 TI - Ischemic injury induces altered MHC gene expression in kidney by an interferon gamma-dependent pathway. PMID- 1899314 TI - Cytokine gene activation in rat lung allografts: analysis by northern blotting. PMID- 1899316 TI - Allogeneic hepatocytes stimulate the production of immunoregulatory molecules in mixed lymphocyte hepatocyte cultures. PMID- 1899315 TI - Effects of Euro-Collins, University of Wisconsin, and histidine-tryptophane ketoglutarate solution on hepatic microcirculation following liver transplantation in the rat. PMID- 1899317 TI - Conservative management complications after thrombolytic therapy. PMID- 1899318 TI - Recombinant tissue-type plasminogen activator: current concepts and guidelines for clinical use in acute myocardial infarction. Part II. AB - The extraordinarily high prevalence of coronary heart disease, coupled with the alarming incidence of MI in Western society, has encouraged the investigation and development of pharmacologic agents that can be employed widely, quickly, effectively, and safely. Recombinant t-PA has played a vital role in the treatment of MI, restoring coronary arterial patency, limiting infarct size, preserving ventricular function, and improving patient survival. It has been shown to be safe when given to carefully selected patients and, although indications for clinical use have been relatively restricted, they appear to be expanding considerably. Future investigations must continue to focus on patient selection to allow treatment for all patients who would derive benefit and to establish dosing regimens and adjuvant therapies that will maximize coronary reperfusion while concomitantly limiting reocclusion and hemorrhagic complications. PMID- 1899319 TI - Complete atrioventricular block complicating inferior wall acute myocardial infarction treated with reperfusion therapy. TAMI Study Group. AB - Previous studies report larger myocardial infarcts and increased in-hospital mortality rates in patients with inferior wall acute myocardial infarction (AMI) and complete atrioventricular block (AV), but the clinical implications of these complications in patients treated with reperfusion therapy have not been addressed. The clinical course of 373 patients--50 (13%) of whom developed complete AV block--admitted with inferior wall AMI and given thrombolytic therapy within 6 hours of symptom onset was studied. Acute patency rates of the infarct artery after thrombolytic therapy were similar in patients with or without AV block. Ventricular function measured at baseline and before discharge in patients with complete AV block showed a decrement in median ejection fraction (-3.5 vs 0.4%, p = 0.03) and in median regional wall motion (-0.14 vs +0.24 standard deviations/chord, p = 0.05). The reocclusion rate was higher in patients with complete AV block (29 vs 16%, p = 0.03). Patients with complete AV block had more episodes of ventricular fibrillation or tachycardia (36 vs 14%, p less than 0.001), sustained hypotension (36 vs 10%, p less than 0.001), pulmonary edema (12 vs 4%, p = 0.02) and a higher in-hospital mortality rate (20 vs 4%, p less than 0.001), although the mortality rate after hospital discharge was identical (2%) in the 2 groups. Multivariable logistic regression analysis revealed that complete AV block was a strong independent predictor of in-hospital mortality (p = 0.0006). Thus, despite initial successful reperfusion, patients with inferior wall AMI and complete AV block have higher rates of in-hospital complications and mortality. PMID- 1899320 TI - Rapid detection of the A----G(8344) mutation of mtDNA in Italian families with myoclonus epilepsy and ragged-red fibers (MERRF). AB - We devised a rapid PCR-based method to screen for an A----G transition at nucleotide 8344 of the human mitochondrial tRNA(Lys) gene, which was recently reported, by Shoffner and co-workers, to be associated with myoclonus epilepsy and ragged-red fibers (MERRF), a maternally transmitted mitochondrial encephalomyopathy (Shoffner et al. 1990). We confirmed this association in five of seven Italian MERRF pedigrees. The mutation was specific for the MERRF trait, because it was never found in mtDNA of non-MERRF individuals, including 14 normal and 110 diseased controls. Our study corroborates the idea that the A----G(8344) mutation is the most frequent and widespread genetic cause of MERRF. PMID- 1899321 TI - Homozygous tyrosinase gene mutation in an American black with tyrosinase-negative (type IA) oculocutaneous albinism. AB - We have identified a tyrosinase gene mutation in an American black with classic, tyrosinase-negative oculocutaneous albinism. This mutation results in an amino acid substitution (Cys----Arg) at codon 89 of the tyrosinase polypeptide. The proband is homozygous for the substitution, suggesting that this mutation may be frequently associated with tyrosinase-negative oculocutaneous albinism in blacks. PMID- 1899322 TI - Discharges against medical advice at regional acute care hospitals. AB - Data from 67 acute care hospitals in the Philadelphia metropolitan area indicate that there were 7,613 discharges against medical advice (AMA) in fiscal year 1987, or 1.20 percent of all discharges that year. Diagnosis-related group (DRG), type of insurance, and sex had independent effects on the rate of AMA discharges. Urban community hospitals had the highest percent of AMA discharges. Previous studies, done in teaching facilities, may have underestimated the rate of AMA discharges. PMID- 1899323 TI - Long-term care for the functionally dependent elderly. PMID- 1899324 TI - Progress in cancer. AB - Definite progress has been made against cancer since the National Cancer Act was passed in 1971. Physicians are giving increased attention to cancer prevention. The exciting changes in molecular biology provide increased knowledge about basic mechanisms in tumor growth and metastases. Detailed discussions of two common solid cancers--breast and colorectal--attest to continuing advances in cancer diagnosis and treatment. All of these augur well for further progress in oncology. Continued research, basic and clinical, is mandatory. PMID- 1899325 TI - Effect of theophylline on sleep and sleep-disordered breathing in patients with chronic obstructive pulmonary disease. AB - To investigate the effect of theophylline on sleep and sleep-disordered breathing in patients with chronic obstructive pulmonary disease (COPD), we studied 12 male nonhypercapnic subjects with a mean +/- SEM age of 62.8 +/- 2.5 yr and a FEV1 of 1.36 +/- 0.11 L using a randomized double-blind crossover protocol. Sustained action theophylline (250 mg three times or four times a day) or placebo was administered for 2 days, and the alternate drug was administered on the following 2 days. Sleep studies were performed on Nights 2 and 4 with spirometry at 9:00P.M. and 7:00A.M. Two puffs of metaproterenol or albuterol were administered at 10:00P.M. on both study nights. A theophylline level, drawn at bedtime (10:00 to 11:00P.M.), was 14.2 +/- 0.78 micrograms/ml on the theophylline nights and less than 2 on placebo nights. The morning FEV1 was significantly better during theophylline administration (1.27 +/- 0.12 versus 1.00 +/- 0.11 L, p less than 0.001). The mean arterial oxygen saturation (SaO2) and transcutaneous carbon dioxide pressure (PCO2) were also better during NREM sleep on theophylline nights. Neither the mean SaO2 and transcutaneous PCO2 during REM sleep nor the apnea plus hypopnea index (events per hour of sleep) differed between placebo and theophylline nights. Theophylline administration did not impair the amount or architecture of sleep as neither total sleep time nor the fraction of time spent in Stages 1, 2, and 3/4 and REM differed between the two regimens. The number of arousals per hour of sleep was slightly less on theophylline nights (19.9 +/- 1.7 versus 24.9 +/- 2.7, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1899326 TI - Comparison of bacteriostatic and bactericidal activity of isoniazid and ethionamide against Mycobacterium avium and Mycobacterium tuberculosis. AB - Minimal inhibitory and bactericidal concentrations (MIC and MBC) of isoniazid and ethionamide were determined in 7H12 broth in experiments with 68 Mycobacterium avium strains and 14 wild drug-susceptible M. tuberculosis strains. MICs of isoniazid for M. tuberculosis were from 0.025 to 0.05 microgram/ml, and for M. avium from 0.6 to greater than 10.0 micrograms/ml. MICs of ethionamide for M. tuberculosis were from 0.3 to 1.25 micrograms/ml, and 42.7% of M. avium strains were within the same range. Isoniazid and ethionamide were highly bactericidal against M. tuberculosis, but they had very low bactericidal activity against M. avium. PMID- 1899327 TI - Primary prophylaxis against common infectious diseases in persons with human immunodeficiency virus infection. PMID- 1899328 TI - alpha,beta-Dehydro-3,4-dihydroxyphenylalanine derivatives: rate and mechanism of formation. AB - The amino acid L-3,4-dihydroxyphenylalanine (DOPA), when present in the primary sequence of proteins, does not form melanin upon oxidation to the quinone, since its amine moiety participates in a peptide bond and cannot undergo internal cyclization. Instead, peptidyl DOPA quinone is available for other reactions. We have investigated the oxidation chemistry of a low molecular weight peptidyl DOPA analog, N-acetylDOPA ethyl ester (NAcDEE), and have shown that a major product of oxidation is an unsaturated DOPA derivative, N-acetyl-alpha,beta-dehydroDOPA ethyl ester (NAc delta DEE) (see companion paper, Rzepecki et al., Arch. Biochem. Biophys. (1991) 285, 17-26). In the present study, we have explored kinetic and mechanistic features of the conversion of NAcDEE to NAc delta DEE and found that the reaction requires: (i) oxidation of NAcDEE to the quinone, (ii) the presence of a Lewis base as a catalyst (phosphate anion was the best of those tried in the pH range 6.0-8.0), and (iii) prevention of competing reactions such as Michael additions. Conversion efficiencies in the presence of Lewis bases ranged between 12 and 19% at pH 8.0 and 35 and 90% at pH 6.0. At least two separate reaction mechanisms appeared necessary to explain the kinetic data: (i) a pseudo-first order mechanism at pH 6.0 and above, and (ii) an additional second-order mechanism at higher pH which involved both NAcDEE catechol and quinone. The apparent pseudo-first-order rate constants increased with pH from 2.36 X 10(-4) s 1 at pH 6.0 to about 30 X 10(-4) s-1 at pH 8.0 in 0.1 M sodium phosphate. Tautomerization of DOPA quinone to dehydroDOPA may thus be a factor in the sclerotization of natural structures incorporating DOPA containing proteins. PMID- 1899329 TI - Enzymatic conversion of beta-carotene into beta-apo-carotenals and retinoids by human, monkey, ferret, and rat tissues. AB - Whether the conversion of beta-carotene into retinoids involves an enzymatic excentric cleavage mechanism was examined in vitro with homogenates prepared from human, monkey, ferret, and rat tissue. Using high-performance liquid chromatography, significant amounts of beta-apo-12'-, -10'-, and -8'-carotenals, retinal, and retinoic acid were found after incubation of intestinal homogenates of the four different species with beta-carotene in the presence of NAD+ and dithiothreitol. No beta-apo-carotenals or retinoids were detected in control incubations done without tissue homogenates. The production of beta-apo carotenals was linear for 30 min and up to tissue protein concentrations of 1.5 mg/ml. The rate of formation of beta-apo-carotenals from 2 microM beta-carotene was about 7- to 14-fold higher than the rate of retinoid formation in intestinal homogenates, and the rate of beta-apo-carotenal production was fivefold greater in primate intestine vs rat or ferret intestine (P less than 0.05). The amounts of beta-apo-carotenals and retinoids formed were markedly reduced when NAD+ was replaced by NADH, or when dithiothreitol and cofactors were deleted from the incubation mixture. Both beta-apo-carotenal and retinoid production from beta carotene were inhibited completely by adding disulfiram, an inhibitor of sulfhydryl-containing enzymes. Incubation of beta-carotene with liver, kidney, lung, and fat homogenates from each species also resulted in the appearance of beta-apo-carotenals and retinoids. The identification of three unknown compounds which might be excentric cleavage products is ongoing. These data support the existence of an excentric cleavage mechanism for beta-carotene conversion. PMID- 1899330 TI - Exacerbation of psoriasis by chrysotherapy. PMID- 1899331 TI - Atrophie blanche in a patient with gamma-heavy-chain disease. PMID- 1899332 TI - Somatosensory and magnetic evoked potentials in a postoperative paraparetic patient: case report. AB - Somatosensory evoked potential (SSEP) testing is increasingly being used to test for spinal cord injuries and to monitor spinal surgery to reduce the risk of paraplegia. It is a sensory test, but it is assumed that any process severe enough to affect the motor tracts will also affect the sensory tracts and, therefore, be identified. Increasingly, however, isolated motor-tract involvement has been reported. A new technique, magnetic coil stimulation of the cortex, directly monitors the motor tracts. We report a case where the SSEP was normal although the magnetic motor-evoked potential was abnormal, supporting the hypothesis that direct testing of motor tracts may be advantageous. PMID- 1899333 TI - Expression and maturation of human cathepsin D in baby-hamster kidney cells. AB - In medium and in homogenates from baby-hamster kidney cells (BHK) transfected with human cathepsin D cDNA, an elevated activity of cathepsin D was found as compared to non-transfected cells. The elevated activity was removed by titrating the homogenates with an anti-(human cathepsin D) antibody. Metabolic labelling and immunoprecipitation revealed that, in the transfected cells, human cathepsin D was synthesized as a 53-kDa precursor indistinguishable from that found in human cells. A portion of the precursor was secreted and the remainder was processed to intermediate and mature chains within a few hours of synthesis. The precursor that was released from the transfected cells had a slightly smaller apparent size than that from cultured human fibroblasts. This difference was abrogated when the precursors were treated with glycopeptidase F. In the intracellular small chain a difference was observed in the size of carbohydrate chains that were cleavable with endo-beta-N-acetylglucosaminidase H. Sequence analysis of the N-termini of mature intracellular cathepsin D indicated a N terminal trimming in both large and small chains from both human and transfected hamster cells. The proteolytic maturation of human cathepsin D in BHK cells closely resembles that in human cells, whereas a portion of the carbohydrate side chains is processed differently. The trimming of the N-termini in mature cathepsin D is proposed to be a part of the maturation and aging of this protein. PMID- 1899334 TI - Synthesis of intracellular histamine in platelets is associated with activation of protein kinase C, but not with mobilization of Ca2+. AB - In previous reports, we have provided evidence indicating that newly formed histamine is an intracellular messenger in human platelets. The involvement of protein kinase C (PKC) and intracellular calcium (Ca2+i) in the synthesis of histamine was investigated. Human platelets were stimulated by phorbol 12 myristate 13-acetate (PMA), collagen and the Ca2+ ionophore A23187, with or without the PKC inhibitor staurosporine. Aggregation, histamine synthesis and phosphorylation of pleckstrin (47 kDa; P47) and myosin light chain (20 kDa; P20) proteins were monitored. Staurosporine inhibited PMA- and collagen-induced aggregation, histamine synthesis and phosphorylation of 47 kDa and 20 kDa proteins in a dose-dependent manner. For PMA, median inhibitory concentrations (IC50 values) for staurosporine inhibition of aggregation, histamine synthesis and phosphorylation were similar, suggesting that histamine synthesis induced by this agonist may be a consequence of PKC activation. Conversely, collagen stimulated histamine synthesis was inhibited by staurosporine at concentrations significantly higher than those required to inhibit aggregation (P less than 0.005) or pleckstrin phosphorylation (P less than 0.01), indicating the possible involvement of non-PKC mechanism(s) in the synthesis of histamine induced by this agonist. A23187 failed to induce the synthesis of intracellular histamine in platelets, whereas staurosporine blocked A23187-induced aggregation and phosphorylation of the 20 kDa protein at significantly higher concentrations than those needed to inhibit PKC. When platelets were stimulated with a combination of A23187 and PMA, the increase in platelet histamine was less than that with PMA alone. The results provide evidence that the synthesis of intracellular histamine in platelets occurs as a consequence of PKC activation and may be down-regulated under conditions where there is a substantial rise in [Ca2+]i. PMID- 1899336 TI - Heterogeneity of mutations in the acid beta-glucosidase gene of Gaucher disease patients. AB - Gaucher disease is inherited in an autosomal recessive manner and is the most prevalent lysosomal storage disease. Gaucher disease has marked phenotypic variation and molecular heterogeneity, and several simple and complex alleles of the acid beta-glucosidase gene have been identified as causal to this disease. Certain combinations of alleles have been shown to correlate well with the severity of the disease, but many Gaucher disease patients exist whose disease is not explained by any of the published mutations. This study was undertaken to identify mutant alleles in such incompletely characterized Gaucher disease, in an attempt to find further correlations between clinical phenotype and the presence of acid beta-glucosidase alleles. RNA was isolated from Gaucher cell lines and converted to cDNA, the cDNA was amplified by PCR and cloned, and several clones for each allele were sequenced. Several new singly mutated and multiply mutated alleles were identified, and sequence-specific oligonucleotide hybridization was used to verify the presence of these mutations in the genome of these patients. All newly identified mutations occurred only rarely in the Gaucher disease population, making it difficult to determine whether inheritance of a particular combination of alleles always correlates with the clinical manifestations seen in the test patients. Three of the newly described alleles were single missense mutations in exon 8, one was a single missense mutation in exon 5, and the fifth was a complex allele, comprising a series of different point mutations scattered throughout exons 5 and 6.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1899335 TI - Expression of c-jun, jun B and jun D proto-oncogenes in human peripheral-blood granulocytes. AB - We have found that purified human peripheral-blood granulocytes express constitutively significant levels of proto-oncogenes c-jun, jun B and jun D mRNA. Upon functional activation of granulocytes by 4 beta-phorbol 12-myristate 13 acetate (PMA), the levels of c-jun, jun B and jun D transcripts were increased. The three jun genes showed a similar time course in their induction by PMA, maximal mRNA levels being reached after 60 min of induction. These results suggest that expression of c-jun, jun B and jun D genes might be involved in terminal granulocyte differentiation or in regulating granulocyte functionality. PMID- 1899337 TI - Sulfated O-glycoproteins secreted by guinea pig trachea in organ culture. AB - Organ culture of guinea pig trachea was performed in the presence of [35S]sulfate in order to characterize the sulfated glycoproteins released from the respiratory epithelium and mucosa. The sulfated macromolecules that were synthesized during a 6-h incorporation were separated by CsBr density-gradient centrifugation and gel filtration chromatography successively. Most of the sulfated secreted macromolecules corresponded to a population of glycoproteins sensitive to reductive beta-elimination but resistant to both chondroitinase ABC and heparinase. These glycoproteins had different buoyant densities (ranging from 1.48 g/ml to 1.16 g/ml) and could be subfractionated according to molecular mass. A major part of the radioactivity was incorporated into high-molecular-mass mucins that were excluded from a Sepharose CL-2B column and did not penetrate into polyacrylamide gel in PAGE. However, a mixture of sulfated O-glycoproteins of much lower molecular mass was also characterized in addition to low amounts of chondroitin sulfate. Epithelial goblet cells are the predominant mucin-containing cells of the respiratory guinea pig trachea. Our results suggest that a wide range of sulfated O-glycoproteins are secreted by the guinea pig tracheal mucosa. PMID- 1899338 TI - Age-dependent accumulation of N epsilon-(carboxymethyl)lysine and N epsilon (carboxymethyl)hydroxylysine in human skin collagen. AB - N epsilon-(Carboxymethyl)lysine (CML) is formed on oxidative cleavage of carbohydrate adducts to lysine residues in glycated proteins in vitro [Ahmed et al. (1988) J. Biol. Chem. 263, 8816-8821; Dunn et al. (1990) Biochemistry 29, 10964-10970]. We have shown that, in human lens proteins in vivo, the concentration of fructose-lysine (FL), the Amadori adduct of glucose to lysine, is constant with age, while the concentration of the oxidation product, CML, increases significantly with age [Dunn et al. (1989) Biochemistry 28, 9464-9468]. In this work we extend our studies to the analysis of human skin collagen. The extent of glycation of insoluble skin collagen was greater than that of lens proteins (4-6 mmol of FL/mol of lysine in collagen versus 1-2 mmol of FL/mol of lysine in lens proteins), consistent with the lower concentration of glucose in lens, compared to plasma. In contrast to lens, there was a slight but significant age-dependent increase in glycation of skin collagen, 33% between ages 20 and 80. As in lens protein, CML, present at only trace levels in neonatal collagen, increased significantly with age, although the amount of CML in collagen at 80 years of age, approximately 1.5 mmol of CML/mol of lysine, was less than that found in lens protein, approximately 7 mmol of CML/mol of lysine. The concentration of N epsilon-(carboxymethyl)hydroxylysine (CMhL), the product of oxidation of glycated hydroxylysine, also increased with age in collagen, in parallel with the increase in CML, from trace levels at infancy to approximately 5 mmol of CMhL/mol of hydroxylysine at age 80.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1899339 TI - Isolation of estradiol-2,3-quinone and its intermediary role in melanin formation. AB - We have reported previously that 2-hydroxyestradiol can be oxidized in the presence of catechol by mushroom tyrosinase, with a stoichiometric requirement of molecular oxygen (Jacobsohn, G.M. and Jacobsohn, M.K. (1984) Arch. Biochem. Biophys. 232, 189-196). It is then incorporated into melanin (Jacobsohn et al. (1988) J. Steroid Biochem. 31, 377-385). We now report on the isolation and characterization of the o-quinone as a product of the enzyme reaction from 2 hydroxyestradiol. The o-quinone was isolated from incubates and identified by its FTIR spectrum, in particular, by the appearance of a new band at 1652 cm-1, its migration in HPLC systems, its ultraviolet spectrum, its derivatization with phenylenediamine and comparison of these properties with the periodate oxidation product of the same substrate. The enzyme oxidation of the catechol estrogen was performed at 37 degrees C and did not require an activator; dopa at concentrations higher than 5 microM was inhibitory. At concentrations lower than 5 microM, dopa acted catalytically and was not consumed during the course of reaction. Ascorbic acid inhibited the reaction. The quinone exhibited both reversible and irreversible binding to performed melanin and to melanin actively synthesized by the enzyme. Incubation of 18 microM newly synthesized [4 14C]estradiol-2,3- quinone with mushroom tyrosinase for 45 min at 37 degrees C in presence of 400 microM dopa showed incorporation (irreversible binding) of 6.3 +/ 0.3% of label into melanin produced during the course of reaction. Similar incubations for 45 min of pre-formed melanin prepared from 400 microM dopa showed incorporation of 4.4 +/- 0.2% of the label. Reversible binding was 10-times greater than incorporation for both actively synthesized and preformed melanins. In the absence of dopa or catechol, enzyme incubations of either 2-hydroxy estradiol or its quinone did not yield melanin. Data suggest that estradiol-2,3 quinone is an intermediate in the incorporation of the catechol estrogen into melanin by tyrosinase. PMID- 1899341 TI - Purification and properties of an extreme thermostable glutamate dehydrogenase from the archaebacterium Sulfolobus solfataricus. AB - Glutamate dehydrogenase (L-glutamate:NAD(P)+ oxidoreductase, deaminating, EC 1.4.1.3.) of the extreme thermophilic archaebacterium Sulfolobus solfataricus was purified to homogeneity by (NH4)2SO4 fractionation, anion-exchange chromatography and affinity chromatography on 5'-AMP-Sepharose. The purified native enzyme had a Mr of about 270,000 and was shown to be a hexamer of subunit Mr of 44,000. It was active from 30 to 95 degrees C, with a maximum activity at 85 degrees C. No significant loss of enzyme activity could be detected, either after incubation of the purified enzyme at 90 degrees C for 60 min, or in the presence of 4 M urea or 0.1% SDS. The enzyme was catalytically active with both NADH and NADPH as coenzyme and was specific for 2-oxoglutarate and L-glutamate as substrates. With respect to coenzyme utilization the Sulfolobus solfataricus glutamate dehydrogenase resembled more closely the equivalent enzymes from eukaryotic organisms than those from eubacteria. PMID- 1899340 TI - Synthesis and processing of lysosomal alpha-fucosidase in cultured human fibroblasts. AB - The lysosomal enzyme alpha-L-fucosidase from human skin fibroblasts is synthesized as a 53 kDa glycosylated precursor which is then proteolytically processed to a 50 kDa mature form. This was confirmed by pulse-chase labeling studies with chase times up to 72 h. In fibroblasts treated with 1 deoxymannojirimycin to prevent trimming of high mannose oligosaccharides, endoglycosidase H (endo H) treatment completely deglycosylated and reduced the size of immunoprecipitated alpha-fucosidase by 4-5 kDa, suggesting the presence of two oligosaccharide units. Endoglycosidase H and endo F studies on untreated alpha-fucosidase suggested the presence of one complex-type and one high mannose type unit, and that the final processing from 53 to 50 kDa did not involve the removal of carbohydrate. Processing was inhibited by the thiol proteinase inhibitor Ep-459, but not by Ep-475 or leupeptin. Since Ep-459 treatment increased both alpha-fucosidase activity (3-fold) and the amount of immunoprecipitable alpha-fucosidase protein in normal human skin fibroblasts, this suggests a role for cysteine-like proteinases either directly or indirectly in lysosomal hydrolase processing and turnover. Subcellular fractionation studies revealed that the proteolytic processing of the 53 kDa precursor to the 50 kDa mature form occurred in the lysosome, or some other dense organelle. PMID- 1899342 TI - Isolation and identification of alpha-(beta-alanyl)hypusine from bovine brain. AB - A unique dipeptide was isolated from bovine brain using five steps of ion exchange chromatography. Its acid hydrolysate contained equimolar amounts of beta alanine and hypusine. The structure of the peptide was elucidated as alpha-(beta alanyl)hypusine using dansylation technique. About 1 mumol of the compound was isolated from 1090 g of bovine brain. PMID- 1899343 TI - Mechanism of inhibition of melanogenesis by hydroquinone. AB - Hydroquinone (HQ) is one of the most effective inhibitors of melanogenesis in vitro and in vivo, and is widely used for the treatment of melanosis and other hyperpigmentary disorders. In an attempt to get some insight into the molecular mechanism of the depigmenting action, which is still very poorly understood, we have investigated the effect of HQ on the tyrosinase catalysed conversion of tyrosine to melanin. Incubation of 0.5 mM tyrosine with 0.07 U/ml tyrosinase in phosphate buffer at pH 6.8 in the presence of 0.5 mM HQ led to no detectable melanin formation, due to the preferential oxidation of HQ with respect to tyrosine (HPLC evidence). Kinetic investigations showed that HQ is a poorer substrate of tyrosinase than tyrosine; yet, it may be effectively oxidised in the presence of tyrosine owing to the generation of catalytic amounts of dopa acting as cofactor of tyrosinase. Product analysis of HQ oxidation with tyrosinase in the presence of dopa showed the predominant formation in the early stages of hydroxybenzoquinone (HBQ), arising from enzymic hydroxylation and subsequent oxidation of HQ, along with lower amounts of benzoquinone (BQ). These results suggest that the depigmenting activity of HQ may partly be related to the ability of the compound to act as an alternate substrate of tyrosinase, thereby competing for tyrosine oxidation in active melanocytes. PMID- 1899344 TI - Double hydroperoxidation of alpha-linolenic acid by potato tuber lipoxygenase. AB - The potato tuber lipoxygenase preparations convert alpha-linolenic acid not only to 9(S)-HPOTE, but also to some more polar metabolites. Two of these polar products, I and II, with ultraviolet absorbance maxima at 267 nm were purified by HPLC. It was found that metabolites I and II have, respectively, one and two hydroperoxy groups. Products of NaBH4 reduction of both I and II were identified by their chemical ionization and electron impact mass spectra and by 1H-NMR spectra as 9,16-dihydroxy-10(E), 12(Z), 14(E)-octadecatrienoic acid. The obtained results suggest that compound II is 9.16-dihydroperoxy-10(E), 12(Z), 14(E) octadecatrienoic acid and product I is a mixture of two positional isomers, 9 hydroxy-16-hydroperoxy-10(E),12(Z),14(E)-octadecatrienoic and 9-hydroperoxy-16 hydroxy-10(E),12(Z),14(E)-octadecatrienoic acids. Lipoxygenase converts efficiently [14C]9-HOTE into product I. Also, both metabolites I and II are the products of double dioxygenation. The second oxygenation at C-16 position as well as the first one at C-9 is controlled by lipoxygenase. PMID- 1899345 TI - Role of pertussis toxin-sensitive guanosine triphosphate-binding proteins in the response of erythroblasts to erythropoietin. AB - Human progenitor-derived erythroblasts have been recently shown to respond to erythropoietin (Epo) with an increase in intracellular free calcium concentration [Cac]. To explore the role of guanosine triphosphate (GTP)-binding proteins in mediating the rise in [Cac], single day 10 erythroid burst forming unit (BFU-E) derived erythroblasts loaded with Fura-2 were pretreated with pertussis toxin (PT), stimulated with Epo, and [Cac] measured over 18 minutes with fluorescence microscopy coupled to digital video imaging. The [Cac] increase in day 10 erythroblasts stimulated with Epo was blocked by pretreatment with PT in a dose dependent manner but not by heat-inactivated PT. These observations provided strong evidence that a PT-sensitive GTP-binding protein is involved. To further characterize the GTP-binding protein, day 10 erythroblast membrane preparations were solubilized, electrophoresed, and immunoblotted with antibodies specific for the known PT-sensitive G-protein subunits: the three subtypes of Gia (1,2, and 3) and Goa, Gia1 or Gia3 and Gia2 were identified but no Goa was found. To examine the influence of Epo on adenylate cyclase activity, day 10 erythroblasts were initially treated with Epo, isolated membrane preparations made, and cyclic adenosine monophosphate (cAMP) production by adenylate cyclase in membrane preparations in the presence of theophylline measured. Epo did not inhibit but significantly stimulated adenylate cyclase activity. However, the mechanism of increase of [Cac] appears to be independent of adenylate cyclase stimulation because treatment of erythroblasts with the cell-permeant dibutyryl cAMP failed to increase [Cac]. In summary, pertussis toxin blocks the increase in [Cac] in erythroblasts after Epo stimulation suggesting that this response is mediated through a pertussis toxin-sensitive GTP-binding protein. Candidate PT-sensitive GTP-binding proteins identified on day 10 erythroblasts were Gia 1, 2, or 3, but not Goa. PMID- 1899346 TI - Time-dependent association between platelet-bound fibrinogen and the Triton X-100 insoluble cytoskeleton. AB - Previous studies indicated a correlation between the formation of EDTA-resistant (irreversible) platelet-fibrinogen interactions and platelet cytoskeleton formation. The present study explored the direct association of membrane-bound fibrinogen with the Triton X-100 (Sigma Chemical Co, St Louis, MO) insoluble cytoskeleton of aspirin-treated, gel-filtered platelets, activated but not aggregated with 20 mumol/L adenosine diphosphate (ADP) or 150 mU/mL human thrombin (THR) when bound fibrinogen had become resistant to dissociation by EDTA. Conversion of exogenous 125I-fibrinogen to fibrin was prevented by adding Gly-Pro-Arg and neutralizing THR with hirudin before initiating binding studies. After 60 minutes at 22 degrees C, the cytoskeleton of ADP-treated platelets contained 20% +/- 12% (mean +/- SD, n = 14) of membrane-bound 125I-fibrinogen, representing 10% to 50% of EDTA-resistant fibrinogen binding. The THR-activated cytoskeleton contained 45% +/- 15% of platelet bound fibrinogen, comprising 80% to 100% of EDTA-resistant fibrinogen binding. 125I-fibrinogen was not recovered with platelet cytoskeletons if binding was inhibited by the RGDS peptide, excess unlabeled fibrinogen, or disruption of the glycoprotein (GP) IIb-IIIa complex by EDTA-treatment. Both development of EDTA-resistant fibrinogen binding and fibrinogen association with the cytoskeleton were time dependent and reached maxima 45 to 60 minutes after fibrinogen binding to stimulated platelets. Although a larger cytoskeleton formed after platelet stimulation with thrombin as compared with ADP, no change in cytoskeleton composition was noted with development of EDTA-resistant fibrinogen binding. Examination of platelet cytoskeletons using monoclonal antibodies, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and Western blotting showed the presence of only traces of GP IIb-IIIa in the cytoskeletons of resting platelets, with no detectable increases after platelet activation or development of EDTA-resistant fibrinogen binding. These data suggest that GP IIb-IIIa-mediated fibrinogen binding to activated platelets is accompanied by time-dependent alterations in platelet fibrinogen interactions leading to the GP IIb-IIIa independent association between bound fibrinogen and the platelet cytoskeleton. PMID- 1899347 TI - A lifelong bleeding disorder associated with a deficiency of plasminogen activator inhibitor type 1. AB - A 36-year-old patient was investigated for a lifelong history of epistaxis and delayed bleeding after minor surgeries. Deficiencies or abnormalities of the coagulation system, of platelet function, or of factor XIII and alpha-2 antiplasmin were excluded. Consistently, however, over a period of 7 years, a high basal euglobulin fibrinolytic activity was observed that was characterized by a high tissue-type plasminogen activator (t-PA) activity, normal t-PA antigen, and undetectable plasminogen activator inhibitor type-1 (PAI-1) antigen and activity. The high specific activity of t-PA (640,000 IU/mg) and the minimal amounts of t-PA/PAI-1 complexes detected by fibrin zymography suggest that in this patient all t-PA was active. This is in striking contrast to normal plasma, where the majority of t-PA is complexed to PAI-1. Thus, in this patient, a severe deficiency of PAI-1 is associated with a delayed type bleeding tendency. Our observation underscores the importance of plasma PAI-1 for the stabilization of the hemostatic plug. PMID- 1899348 TI - Enhancement of the fibrinolytic activity of sheep endothelial cells by retroviral vector-mediated gene transfer. AB - In an attempt to enhance the fibrinolytic activity of endothelial cells (EC), a retroviral vector containing the human tissue-type plasminogen activator (t-PA) cDNA was constructed. Sheep EC were stably transduced with the vector, resulting in a 30-fold increase in t-PA activity over that detected in EC transduced with a control vector. Southern and Northern analyses confirmed the presence of both the vector sequence and the appropriate mRNA transcripts. Secretion of high levels of recombinant human t-PA continued in vitro for the duration of the experiments, up to 11 weeks after transduction, although the rate of t-PA secretion decreased in some of the EC lines. Zymographic analysis of conditioned medium from t-PA transduced EC showed the presence of two new molecular species with plasminogen activator activity that could be specifically immunoprecipitated with a monoclonal antihuman t-PA antibody. The relative molecular masses of these species (60 to 80 and 110 Kd) suggest that they represent recombinant human t-PA both free and bound to sheep plasminogen activator inhibitor 1 (PAI-1). Consistent with this interpretation, the 110-Kd species could be specifically immunoprecipitated with antiserum to PAI-1. These studies demonstrate that retroviral vector-mediated gene transfer may be used to increase total EC fibrinolytic activity. PMID- 1899349 TI - Relation between humoral responses to HIV gag and env proteins at seroconversion and clinical outcome of HIV infection. AB - OBJECTIVE: To study the contribution of the humoral response to HIV-I at seroconversion to disease outcome after 84 months. DESIGN: A retrospective longitudinal study. SETTING: Two haemophilia centres in the United Kingdom. PATIENTS: 88 Haemophiliac patients infected with HIV-I for whom sera were available from before seroconversion and in whom clinical follow up data were available. RESULTS: Kaplan-Meier survival analysis showed a significant difference between a high titre (greater than 1600) p24 antibody response at seroconversion and prolonged time before the development of HIV related disease (p = 0.0008). In contrast, higher titres of antibody to gp120 at seroconversion (greater than 25,600) correlated with more rapid clinical deterioration (p = 0.025). CONCLUSIONS: The first humoral response to HIV proteins at seroconversion is associated with clinical outcome; patients with an initial low titre antibody response to the gagp24 protein have a significantly faster rate of progression to CDC stage IV disease. Patients with a high titre p24 antibody response progress to AIDS more slowly, and these data provide an explanation why p24 antigenaemia is not universally detected in patients with AIDS. It is unclear whether the association between a strong initial p24 antibody response and slower progression of HIV disease is causal and if so whether it is due to viral or host factors. PMID- 1899350 TI - No effect of misoprostol on renal function of rheumatoid patients treated with diclofenac. AB - Non-steroidal anti-inflammatory drugs can reversibly decrease renal function in patients with rheumatoid arthritis (RA). To test whether orally administered prostaglandins could mitigate this decrease, we studied the effect of misoprostol in 24 RA patients during treatment with diclofenac in a randomized, placebo controlled crossover trial. At baseline, 21 patients had a creatinine clearance below 80 ml/min/1.73 m2. The two treatment phases (with either misoprostol, 600 micrograms daily, or matching placebo tablets) were separated by a washout phase in which diclofenac (150 mg daily) was continued. After treatment with misoprostol/diclofenac the glomerular filtration rate was 72 +/- 5 ml/min (mean +/- standard error), and the effective renal plasma flow was 295 +/- 21 ml/min. After treatment with placebo/diclofenac, the corresponding values were 71 +/- 5 ml/min and 296 +/- 21 ml/min, respectively. We concluded that misoprostol has no effect on the renal function of RA patients treated with diclofenac. PMID- 1899351 TI - Genes beneficial in autoimmune disease. PMID- 1899352 TI - Ifosfamide continuous infusion without mesna. A phase I trial of a 14-day cycle. AB - Twenty patients received 27 courses of ifosfamide administered as a 24-hour continuous infusion for 14 days without Mesna. The goal of the study was to deliver a dose rate and total cumulative dose of ifosfamide that would be comparable to standard bolus or short-term infusions administered with Mesna. Dose escalations proceeded from 200 to 300, 400, 450, 500, and 550 mg/m2/d. Four patients developed transient microscopic hematuria at 400, 450, and 500 mg/m2/d. There were no instances of macroscopic hematuria. At 550 mg/m2/d, three patients experienced nonurologic toxicity; confusion (1), nausea (1), and Grade 2 leukopenia (1). The recommended dose of 500 mg/m2/d delivers a total dose of 7 g/m2 per cycle, which is comparable to that delivered in clinical practice for bolus or short-term infusion. Because few patients received multiple courses over time, the cumulative effects are indeterminate in the present trial. The frequency and predictability of hematuria are not precise, and at least daily monitoring by urine Hematest is essential, adding Mesna to the infusate in patients with persistent hematuria. The protracted infusion schedule for ifosfamide permits convenient outpatient administration without Mesna and reduces the drug cost of clinical usage of this agent by up to $890 per cycle. Clinical activity was demonstrated in a single patient, but a comparative trial of standard bolus schedules with the protracted infusion schedule will be necessary to determine if the clinical effectiveness of the drug is maintained. PMID- 1899353 TI - Mitomycin C-loaded microcapsules in the treatment of colorectal liver metastases. Pharmacokinetics of regionally administered particulate chemotherapy. AB - Microencapsulated mitomycin C has been used for the treatment of intrahepatic tumors in Japan, but there have been no reports of its use in western countries. In this study, the pharmacokinetic profile of intrahepatic arterial mitomycin C microcapsules is reported. Regional mitomycin C was administered to six patients, both in the microencapsulated form and in solution. The clearance (140 +/- 31 1/hour, mean +/- SD) and half-life of drug in plasma (0.39 +/- 0.03 hours), and volume distribution (246 +/- 23 1) were significantly higher, and peak drug concentrations (80 +/- 75 ng/ml) significantly lower with the microencapsulated preparation than with the free drug (clearance, 46 +/- 8 1/hour; half-life, 0.11 +/- 0.02 hours; volume distribution, 33 +/- 4; peak drug concentration, 812 +/- 423 ng/ml), on Student's t testing (P less than 0.05). The results show that very little systemic exposure is associated with the microencapsulated form of mitomycin C. Dose escalation should be feasible without increasing systemic toxicity. PMID- 1899355 TI - Diagnostic imaging in cancer care. The role of cost/benefit analysis. AB - As the cost of medical care rises, there is increasing need to analyze the costs and benefits of diagnostic imaging. A review of previous research shows reasonable success at defining costs and the ability to identify safety and risk, but limited data on defining benefits in economic terms. The technology to analyze costs and benefits is improving, and satisfactory research protocols and methods have recently become generally accepted. While research studies to determine costs and benefits or efficacy are themselves costly, time consuming, and difficult to perform in clinical practice, the wise allocation of medical resources in the US requires physicians in all specialties to evaluate the technology when we are responsible for its use. PMID- 1899354 TI - Screening mammography. AB - Screening mammography can reduce mortality from breast cancer and is the only means of detecting nonpalpable cancers that are often more curable. Based on this, guidelines have evolved but compliance with them has been slow. Reservations are based on yield-cost-benefit-harm considerations, but uniformed and/or disadvantaged women and reluctance if not resistance to screening mammography by primary care physicians are major problems. The challenges are to overcome these obstacles and to obtain sufficient competent personnel and facilities to make reproducibly optimum screening mammography, which is accurately interpreted, widely available to all eligible women at the lowest possible cost. PMID- 1899356 TI - Cholelithiasis after treatment for childhood cancer. AB - The authors evaluated the risk of development of cholelithiasis in 6050 patients treated at a single hospital for various childhood cancers with different therapeutic modalities, including chemotherapy, surgery, radiation therapy, and bone marrow transplantation, from 1963 to 1989. Patients with underlying chronic hemolytic anemia or preexisting gallstones were excluded. Nine female and seven male patients with a median age of 12.4 years (range, 1.2 to 22.8 years) at diagnosis of primary cancer had gallstones develop 3 months to 17.3 years (median, 3.1 years) after therapy was initiated. Cumulative risks of 0.42% at 10 years and 1.03% at 18 years after diagnosis substantially exceed those reported for the general population of this age group. Treatment-related factors significantly associated with an increased risk of cholelithiasis were ileal conduit, parenteral nutrition, abdominal surgery, and abdominal radiation therapy (relative risks and 95% confidence intervals = 61.6 [27.9-135.9], 23.0 [9.8 54.1], 15.1 [7.1-32.2], and 7.4 [3.2-17.0], respectively). There was no correlation with the type of cancer, nor was the frequency of conventional predisposing features (e.g., family history, obesity, use of oral contraceptives, and pregnancy) any higher among the affected patients in this study than in the general population. Patients with cancer who have risk factors identified here should be monitored for the development of gallstones. PMID- 1899357 TI - Cooperative binding of Drosophila heat shock factor to arrays of a conserved 5 bp unit. AB - Drosophila heat shock factor (HSF) exists as a multimer in solution and when bound to its regulatory element (HSE). We have previously reported evidence that subunits of HSF associate to form homotrimers and that each subunit contacts a conserved 5 bp DNA sequence repeated within an HSE. Here we show that HSF binding is highly cooperative at two distinct levels: between subunits of the HSF multimer, and between multimers. The binding of HSF to one of a pair of adjacent trimeric binding sites facilitates HSF binding to the second by over 2000-fold. This cooperativity is particularly important in binding HSF at 37 degrees C, and could account for the requirement for multiple binding sites in vivo and, in part, for the differential expression of heat shock genes. PMID- 1899358 TI - Preferential inhibition of the oncogenic form of RasH by mutations in the GAP binding/"effector" domain. AB - The double mutation, D33H/P34S, reduced the transforming activity of oncogenic RasH proteins, G12V and Q61L, 400- and 20-fold, respectively. Remarkably, this same mutation did not reduce the transforming activity of normal RasH, nor did it impair the ability of the protein to restore a functional Ras pathway in cells whose endogenous Ras proteins were inhibited. Another mutation in this region, D38N, had similar effects. The mutations reduced downstream coupling efficiency of normal Ras as assessed by yeast adenylyl cyclase stimulation. However, this was offset by decreased GTPase activating protein (GAP) binding, since the latter resulted in elevated GTP-bound mutant Ras in cells. The mutations produced a similar decrease in downstream coupling efficiency of oncogenic Ras, but decreased GAP binding did not compensate because the GTPase activity of oncogenic Ras is not stimulated by GAP. These results imply that preferential inactivation of oncogenic Ras in human tumors may be achieved by reagents designed to inhibit the GAP-binding/"effector" domain of Ras proteins. PMID- 1899359 TI - Induction of interferon-gamma by cord blood mononuclear cells is calcium dependent. AB - Human cord blood mononuclear cells (MNCs) are deficient in their ability to produce interferon-gamma (IFN-gamma). Previous studies have shown that phytohemagglutinin (PHA)-stimulated neonatal MNCs produced significantly less IFN gamma than adult PHA-stimulated MNCs. The deficient IFN-gamma production is partly due to the absence of a macrophage-derived soluble mediator. Supernatants from PHA-stimulated adult macrophages and phorbol myristate acetate (PMA) stimulated U937 cells (which were dialyzed prior to culture to remove PMA) increased IFN-gamma production in neonatal PHA-stimulated MNC (14 to 217 units/ml and 14 to 293 units/ml, respectively). The requirement for a soluble macrophage mediator was replaced by the addition of exogenous calcium chloride (CaCl2) to PHA-stimulated cord blood MNCs. The increase in IFN-gamma production by exogenous CaCl2 was blocked by the addition of the calcium channel blocker, manganese chloride (MnCl2). Furthermore, the increased IFN-gamma production by PHA stimulated cord blood MNC in the presence of PHA-stimulated adult macrophage supernatant or PMA-stimulated U937 supernatant was abrogated by the addition of MnCl2, chlorpromazine, and verapamil. These data suggested that the soluble factor produced by PHA-stimulated adult macrophage supernatant and PHA-stimulated U937 supernatant induced IFN-gamma production in PHA-stimulated cord blood MNC by inducing calcium-dependent signals at more than one site. PMID- 1899360 TI - Macrophage binding of cells resistant and sensitive to contact-dependent cytotoxicity. AB - We compared macrophage binding and killing of F5b cells to the binding and killing of P815 mastocytoma cells and to several other nontransformed and transformed cell lines. Formalin fixation of elicited or activated macrophages did not affect binding of F5b or 3T3 cells but did abrogate binding of P815 cells. However, formalin fixation abrogated resident macrophage binding of F5b and 3T3 cells. Therefore, depending on the type of macrophage or target cell, formalin fixation may affect binding. Only the binding of P815 cells was dependent upon activation; macrophage binding of target cells F5b and 3T3 was not. Even though macrophages bound F5b and 3T3 cells, macrophages only mediated contact-dependent cytotoxicity against F5b cells. Macrophages did not kill 3T3 cells. Experiments also compared macrophage binding and killing of the uv-light induced tumor cell lines 1422, 2237, and 2237a46. Only the cell line 2237a46 was susceptible to contact-dependent killing. Both 1422 and 2237 cells were resistant. In contrast, cell lines 2237a46 and 1422 were bound by activated macrophages while 2237 cells were bound poorly. PMID- 1899361 TI - Differential sensitivity of cytotoxic T lymphocytes and lymphokine-activated killer cells to inhibition by L-ornithine. AB - The selective inhibition of murine cytotoxic T lymphocyte (CTL) differentiation in C57B1/6 (B6) anti-DBA/2 mixed leukocyte cultures (MLC) by the amino acid L ornithine (Orn) could not be reversed by addition of up to 1000 U/ml IL-2. Analysis of the effects of Orn on induction of lymphokine-activated killer (LAK cells), using dosages of IL-2 from 10-1000 U/ml and measuring cytolytic activity against two tumor targets (P815 and YAC-1) over the course of 5 days, indicated that LAK cells were not suppressed by Orn. LAK precursors and effector cells were CD8- and ASGM1+, indicating that they were derived from natural killer (NK) cells. We also found that the growth and maintenance of cloned CTL lines were not sensitive to inhibition by Orn; nor was their acquisition of nonspecific cytolytic activity in the presence of high lymphokine concentrations. Thus, induction of naive CTL shows differential susceptibility to Orn inhibition relative to LAK and LAK-like activities by NK and cloned CTL lines in response to IL-2. PMID- 1899362 TI - T cell activation by mycobacterial antigens in inflammatory synovitis. AB - To define which mycobacterial antigens were responsible for the activation of synovial fluid T lymphocytes, acetone-precipitated Mycobacterium tuberculosis (AP MT) antigens were separated into five fractions following polyacrylamide gel electrophoresis and added to the mononuclear cell cultures of patients with inflammatory synovitis. Fractions 2 (50 to 70 kDa) and 5 (less than 28 kDa) resulted in significantly more proliferation than that of fractions 1, 3, and 4. The response to a purified mycobacterial 65-kDa heat shock protein (hsp), which migrated in fraction 2, was highly correlated (r = 0.89, P less than 0.001) with the response to the crude AP-MT. The proliferative response to a different hsp. the Escherichia coli DnaK, by synovial fluid lymphocytes was marginal. Analysis of the synovial fluid T cell response to mycobacterial culture filtrates by T cell Western blotting revealed dominant responses to antigen(s) in the range of 31 to 21 kDa in each responding patient, although no other consistent pattern of T cell activation was noted. Three lines of evidence suggested that the response to the low molecular weight fractions was directed against degradation fragments of the 65-kDa protein. These observations suggest that the activation of T lymphocytes obtained from inflammatory synovial fluids by crude mycobacterial antigens was due in large part to recognition of the 65-kDa mycobacterial hsp. PMID- 1899363 TI - Synergistic action of myocardial oxygen and carbon dioxide in controlling coronary blood flow. AB - A two-part experiment was designed to test the hypothesis that myocardial oxygen and carbon dioxide tensions, as measured by coronary venous oxygen and carbon dioxide tensions, determine coronary blood flow during increases in myocardial oxygen consumption. The left main coronary artery was pump-perfused at constant pressure in closed-chest, anesthetized dogs. Oxygenators in the perfusion circuit permitted control of coronary arterial gas tensions. The steady-state relation between coronary venous oxygen and carbon dioxide tensions and coronary flow at a constant myocardial oxygen consumption was determined by locally altering coronary arterial oxygen and carbon dioxide tensions. Values of coronary venous oxygen and carbon dioxide tensions and coronary flow were also obtained at normal coronary arterial gas tensions during pacing-induced increases in myocardial oxygen consumption. The data yielded a hyperbolic relation among coronary venous oxygen and carbon dioxide tension and coronary flow during constant myocardial metabolism, suggesting a synergistic interaction between myocardial oxygen and carbon dioxide tensions in determining coronary flow. This relation was then used to predict the coronary flow change during pacing-induced increases in myocardial metabolism. Approximately 40% of the flow response during pacing-induced increases in myocardial oxygen consumption was predicted. In conclusion, coronary venous oxygen and carbon dioxide tensions synergistically interact to produce steady-state changes in coronary flow at a constant myocardial oxygen consumption. Changes in myocardial oxygen and carbon dioxide tensions can account for about 40% of the change in coronary flow during moderate changes in myocardial oxygen consumption. PMID- 1899364 TI - Intracerebral hemorrhage, cerebral infarction, and subdural hematoma after acute myocardial infarction and thrombolytic therapy in the Thrombolysis in Myocardial Infarction Study. Thrombolysis in Myocardial Infarction, Phase II, pilot and clinical trial. AB - In the Thrombolysis in Myocardial Infarction, Phase II pilot and clinical trial, 908 patients [326 (35.9%) in the pilot study and 582 (64.0%) in the randomized study] were treated with 150 mg recombinant tissue-type plasminogen (rt-PA) activator in combination with heparin and aspirin, and 3,016 patients [64 (2.1%) in the pilot study and 2,952 (97.9%) in the randomized study] were treated with 100 mg rt-PA in combination with heparin and aspirin. Adverse neurological events occurred in 23 patients treated with 150 mg rt-PA (2.5%) [nine cerebral infarctions (1.0%), 12 intracerebral hemorrhages (1.3%), and two subdural hematomas (0.2%)] and in 33 patients treated with 100 mg rt-PA (1.1%) [20 cerebral infarctions (0.7%), 11 intracerebral hemorrhages (0.4%), and two subdural hematomas (0.1%)]. The difference in adverse neurological events observed comparing the two rt-PA regimens was primarily due to a higher frequency of intracerebral bleeding among patients treated with 150 mg rt-PA (1.3% versus 0.4%, p less than 0.01). Patients with recent (within 6 months) histories of stroke were not eligible for the study, and patients with any history of cerebrovascular disease were declared ineligible early in the study. The small number of patients (89, or 2.3%) with any history of neurological disease, intermittent cerebral ischemic attacks, or stroke who were enrolled before the stricter eligibility criteria were imposed or on the basis of incomplete baseline information experienced an increased frequency of intracerebral hemorrhage compared with patients without such histories (3.4% versus 0.5%). Mortality at 6 weeks after presentation among 23 patients who had intracerebral hemorrhage was 47.8%. Intracerebral hemorrhage is a severe but infrequent complication of rt-PA therapy for acute myocardial infarction. The combined frequency of intracerebral hemorrhage, subdural hematoma, and cerebral infarction after treatment with 100 mg rt-PA is comparable to that observed in other trials with thrombolytic agents in acute myocardial infarction. PMID- 1899365 TI - Nifedipine reduces the incidence of myocardial infarction and transient ischemia in patients undergoing coronary bypass grafting. AB - A randomized study was performed on 104 patients undergoing elective coronary artery bypass grafting to examine whether the infusion of nifedipine (n = 53) reduces the incidence of perioperative myocardial ischemia and necrosis in the early postoperative period. Continuous hemodynamic and three-channel Holter monitoring was performed for 24 hours and serial assessment of serum enzymes and 12-lead electrocardiography were performed for 36 hours postoperatively. Nifedipine (minimum dose, 10 micrograms/kg/hr for 24 hours) was applied from the onset of extracorporal circulation. The control group (n = 51) received nitroglycerin (minimum dose, 1 micrograms/kg/min for 24 hours). Using the combined analyses of electrocardiography and Holter recordings, myocardial ischemia was defined as being either a transient ischemic event (TIE), transient coronary spasm (TCS), or myocardial infarction (MI). The two groups did not differ with respect to preoperative New York Heart Association classification, age, history of myocardial infarction, extracorporal circulation and aortic cross clamp time, number of distal anastomoses, or systemic and pulmonary hemodynamics. The incidence of perioperative myocardial ischemia was substantially lower in the nifedipine than in the nitroglycerin group [TIE: three of 53 patients (6%) versus nine of 50 patients (18%), p less than 0.001; MI: two of 53 patients (4%) versus six of 50 patients (12%), p less than 0.001; and TCS: none of 53 patients (0%) versus two of 50 patients (4%), p = NS].(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1899366 TI - Introduction of vascular smooth muscle cells expressing recombinant genes in vivo. AB - Vascular smooth muscle cells contribute to the formation of atherosclerotic plaques by proliferating in response to vascular injury and releasing growth promoting factors. Because their autocrine and paracrine effects are not fully understood, expression of such growth factor genes in specific cell types in vivo would help to determine their mechanism of action. We describe a method to transfer vascular smooth muscle cells expressing recombinant gene products to localized segments of the arterial wall. Vascular smooth muscle cells from the inbred Yucatan minipig were infected in vitro with an amphotropic, replication defective retrovirus transducing the gene for Escherichia coli beta galactosidase. Vascular smooth muscle cells expressing this recombinant gene were implanted, using a catheter, into denuded iliofemoral artery segments of pigs in vivo. These arteries subsequently demonstrated beta-galactosidase activity in cells of the intima and media. This method, which provides for the introduction of genetically modified smooth muscle cells, can be used to define the biological effects of recombinant genes in the vessel wall and potentially to provide alternative treatments of vascular diseases. PMID- 1899367 TI - Noninvasive diagnostic assessment of peripheral vascular disease. AB - Noninvasive techniques have assumed an increasingly important role in the management of patients with vascular disease. Both ultrasonic and plethysmographic instruments allow objective evaluation of vascular disorders by the measurement of segmental limb blood pressures, analysis of blood velocity disturbances, recording of digit or limb pulse waveforms, or imaging of vascular disease, with or without Doppler flow analysis or color-flow mapping. These techniques have been applied for screening asymptomatic individuals, diagnosis of symptomatic patients, monitoring of interventional or surgical procedures, and follow-up of the natural history or the efficacy of medical, interventional, or surgical therapy of vascular disease. This article reviews the clinical application of these modalities to patients with peripheral arterial disease and briefly discusses cost-effectiveness and potential abuses of noninvasive technology. PMID- 1899368 TI - Metabolic control in diabetic subjects in three Swedish areas with high, medium, and low sales of antidiabetic drugs. AB - OBJECTIVE: The relationship between use of antidiabetic drugs and metabolic control was studied in Swedish diabetic populations in areas with high (Gotland), medium (Tierp), and low (Skelleftea) sales of antidiabetic drugs. RESEARCH DESIGN AND METHODS: The study population consisted of 405 drug-treated diabetic subjects aged 50-74 yr. In all three areas, glyburide comprised approximately 75% of the oral treatment. RESULTS: In accordance with sales, Gotland was found to be a heavy-use area, characterized by a high prevalence of insulin treatment (43%), combination therapy with sulfonylureas and biguanide (28%), and high prescribed daily doses (PDDs) of glyburide (15.5 +/- 0.8 mg) compared with other areas. In Skelleftea, 38% were on insulin, 4% were on combination therapy, and the PDD of glyburide was 7.1 +/- 0.6 mg. In Tierp, 27% were on insulin, 26% were on combination therapy, and the PDD of glyburide was 11.4 +/- 0.7 mg. In Gotland, both men and women had significantly lower HbA1c levels, regardless of treatment mode, and a tendency to be more overweight compared with the area with the least pharmacological intensity (Skelleftea). CONCLUSIONS: In the three diabetic populations, good metabolic control, defined as an HbA1c level of less than 7% and acceptable weight control (body mass index less than 27 for men and less than 25 for women), was achieved among only 16% in Gotland, 17% in Skelleftea, and 12% in Tierp. PMID- 1899369 TI - Devastating cerebral edema in diabetic ketoacidosis before therapy. PMID- 1899370 TI - Early onset fatal cerebral edema in diabetic ketoacidosis. PMID- 1899371 TI - Regulatory region of human amyloid precursor protein (APP) gene promotes neuron specific gene expression in the CNS of transgenic mice. AB - The accumulation of beta-amyloid protein in specific brain regions is a central pathological feature of Alzheimer's disease (AD). The 4 kd beta-amyloid protein derives from a larger amyloid precursor protein (APP) by as yet unknown mechanisms. In the absence of a laboratory animal model of AD, transgenic mice expressing various APP gene products may provide new insights into the relationship between APP and beta-amyloid formation and the pathogenesis of AD. beta-amyloid accumulation in AD brain may result from interactions between APP and other molecules. Such interactions are likely to be developmentally regulated and tissue-specific. A transgenic mouse model of AD, therefore, would aim for APP transgene expression that mimics the endogenous APP gene. As an initial step in developing an animal model, we have identified a 4.5 kb DNA fragment from the 5' end of the human APP gene, which mediates neuron-specific gene expression in the CNS of transgenic mice, using E. coli lacZ as a reporter gene. Detectable levels of transgene expression are found in most neurons but not in glial and vascular endothelial cells. The expression pattern of this reporter gene closely resembles the distribution of endogenous APP mRNA in both the human and mouse CNS. PMID- 1899372 TI - Transplants of mouse trisomy 16 hippocampus provide a model of Alzheimer's disease neuropathology. AB - Alzheimer's disease, which is characterized by amyloid plaques and neurofibrillary tangles, may be attributed to the abnormal expression of gene(s) located on human chromosome 21. Genetic linkage studies have narrowed the region of candidate genes to 21q11.2-21q22 of the long arm of this chromosome. Several single copy sequences within this region, including the amyloid precursor protein (APP), have been mapped to mouse chromosome 16. Reliable strategies exist for breeding Trisomy 16 mice. However, the consequences of developmental overexpression of genes on chromosome 16 have not been previously investigated, because of the lethal effects of this aneuploidy during gestation. In the present report, we employ neural transplantation to study long-term survival and pathogenesis in Trisomy 16 central nervous system tissues. Immunocytochemical staining with antiserum raised against the synthetic APP, beta-A4 and alpha 1 antichymotrypsin revealed numerous densely stained cells within hippocampal grafts of Trisomy 16 mice. Similarly, a population of grafted cells were positively stained following incubation with an antiserum raised against components of the pathological neurofibrillary tangle and with the monoclonal antibodies Tau 6.423 and ubiquitin. PMID- 1899373 TI - Differentiation of growth signal requirement of B lymphocyte precursor is directed by expression of immunoglobulin. AB - During B cell differentiation, at least three stages can be defined in terms of their growth signal requirement by using two different growth signals, which are recombinant interleukin 7 (IL-7) and a stromal cell clone PA6 which does not produce IL-7; first a PA6 dependent stage, second a PA6 + IL-7 dependent stage and third an IL-7 dependent stage. In order to test the possibility that this differentiation of growth signal requirement is controlled by the expression of functional immunoglobulin molecules, we have investigated the frequencies of PA6 + IL-7 dependent and IL-7 dependent cells which are present in the bone marrow of either mu-chain or kappa-chain gene transgenic mice. In a mu-chain gene transgenic mouse, the frequency of PA6 + IL-7 dependent cells is selectively reduced, while that of IL-7 dependent cells is selectively reduced in a kappa chain gene transgenic mouse. This result suggests that expression of a functional mu-chain gene drives PA6 + IL-7 dependent cells to differentiate into the subsequent IL-7 dependent stage. Likewise, when mu-chain positive IL-7 dependent cells express a functional light-chain gene, their growth signal requirement changes into an IL-7 unreactive stage. PMID- 1899374 TI - A functional role for nucleosomes in the repression of a yeast promoter. AB - Induction of the PHO5 gene in S. cerevisiae was previously shown to be accompanied by the removal of four positioned nucleosomes from the promoter. In order to assess the role of nucleosomes in the cascade of gene activation, DNA corresponding to one of these nucleosomes was excised. In its place two foreign DNA segments of the same length were inserted: a fragment from the African green monkey alpha-satellite DNA which is known to associate with histones in a highly specific fashion to give a uniquely positioned nucleosome or, alternatively, a fragment derived from pBR322 DNA. The promoter constructs were fused to the lacZ gene on centromere plasmids and transformed into yeast cells. The satellite fragment formed a nucleosome which persisted under inducing conditions. At the same time the inducibility of the PHO5 promoter was virtually abolished. When various subfragments containing between 35 and 100 bp of the satellite segment were tested, they were all found to decrease the inducibility of the promoter, full repression required the full length molecule, however. In contrast, the pBR fragment made the promoter weakly constitutive, and induction proceeded to levels even higher than with a promoter lacking an insert. Analysis of the chromatin structure reveals a nucleosome on the pBR segment at noninducing conditions which is removed upon induction. It is concluded that the quality of the histone-DNA interactions at the promoter makes an intrinsic contribution to the regulation of the gene. PMID- 1899375 TI - A conserved heptapeptide restrains the activity of the yeast heat shock transcription factor. AB - In yeast, expression of heat shock genes is regulated by a factor (HSF) which binds constitutively to DNA, but activates transcription efficiently only after heat shock. We have compared the HSFs from Saccharomyces cerevisiae and Kluyveromyces lactis. Both factors contain an activation domain whose activity is masked at low temperature, but the amino acid sequences of these activators are unrelated. Masking requires the evolutionarily conserved DNA binding and oligomerization domains, as well as a short conserved element close to the activator. Although this element contains potential phosphorylation sites, they are not required for induction. We suggest that the conserved element binds either to the structural core of the protein or to another polypeptide, holding the activator in an inactive configuration, and that high temperatures disrupt this interaction. Our results emphasize the importance of global protein structure in the regulation of transcription factor activity. PMID- 1899376 TI - Group II twintron: an intron within an intron in a chloroplast cytochrome b-559 gene. AB - The psbF gene of chloroplast DNAs encodes the beta-subunit of cytochrome b-559 of the photosystem II reaction center. The psbF locus of Euglena gracilis chloroplast DNA has an unusual 1042 nt group II intron that appears to be formed from the insertion of one group II intron into structural domain V of a second group II intron. Using both direct primer extension cDNA sequencing and cDNA cloning and sequencing, we have determined that a 618 nt internal intron is first excised from the 1042 nt intron of psbF pre-mRNA, resulting in a partially spliced pre-mRNA containing a 424 nt group II intron with a spliced domain V. The 424 nt intron is then removed to yield the mature psbF mRNA. Therefore, the 1042 nt intron of psbF is a group II intron within another group II intron. We use the term 'twintron' to define this new type of genetic element. Intermediates in the splicing pathway were detected by northern hybridization. Splicing of both the internal and external introns occurs via lariat intermediates. Twintron splicing was found to proceed by a sequential pathway, the internal intron being removed prior to the excision of the external intron. A possible mechanism for twintron formation by intron transposition is discussed. PMID- 1899378 TI - Hepatocyte heterogeneity in uptake and metabolism of malate and related dicarboxylates in perfused rat liver. AB - 1. In isolated perfused rat liver a near-maximal net malate uptake of about 120 nmol g-1 min-1 was observed at influent malate concentrations above 100 mumol l-1 and a half-maximal uptake at about 50 mumol l-1 in influent. 14CO2 production from added [U-14C]malate paralleled hepatic net malate uptake, however, 14CO2 production exceeded net malate uptake by 20-25%. This was observed in antegrade as well as in retrograde perfusions and regardless of whether NH4Cl was added to the influent perfusate. Stimulation of glutamine synthesis by NH4Cl only slightly affected net malate uptake and 14CO2 production, but resulted in a marked stimulation of [14C]glutamine release from the liver. 2. Because [U-14C]malate uptake by the liver (reflecting the influent/effluent concentration difference of labeled malate) could at least in part involve a malate/malate exchange mechanism, net malate uptake (as determined from the influent/effluent concentration difference of enzymatically assayable malate) may underestimate hepatic [U-14C]malate uptake. On the other hand, during metabolic steady states 14CO2 production from added [U-14C]malate can be considered as an upper limit estimate of [U-14C]malate uptake by the liver. Assuming that 14CO2 production equals [U-14C]malate uptake by the liver, extrapolation studies suggest that during maximal rates of NH4Cl-stimulated glutamine synthesis 80-110% of the [U 14]malate taken up by the liver was used for glutamine synthesis. This was true for retrograde and antegrade perfusions. Similar data, i.e. a 100-130% incorporation regardless of the direction of perfusion, were obtained when [U 14C]malate uptake was assumed to equal net malate uptake by the liver. 3. Substitution of Na+ in the perfusion fluid by choline abolished net malate uptake by the liver and inhibited 14CO2 production from [U-14C]malate by more than 90%. 4. 2-Oxoglutarate inhibited [14C]malate uptake and [1-14C]oxoglutarate uptake by the liver was inhibited by malate, fumarate, succinate and oxaloacetate, but not by aspartate and glutamate. Inhibition of [1-14C]oxoglutarate uptake and of 14CO2 production from added labeled 2-oxoglutarate by malate and fumarate seemed largely competitive. Malate, fumarate and succinate not only inhibited [1 14C]oxoglutarate uptake, but also stimulated the release of unlabeled 2 oxoglutarate from the liver. 5. The data are consistent with a predominant uptake of vascular malate by perivenous glutamine synthetase containing hepatocytes when glutamine synthesis is stimulated to Vmax values by NH4Cl. Malate and other citric acid cycle dicarboxylates, but not aspartate and glutamate, may compete with 2-oxoglutarate for uptake into perivenous glutamine synthesizing hepatocytes.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1899377 TI - Localization of the pathway of the penicillin biosynthesis in Penicillium chrysogenum. AB - The localization of the enzymes involved in penicillin biosynthesis in Penicillium chrysogenum hyphae has been studied by immunological detection methods in combination with electron microscopy and cell fractionation. The results suggest a complicated pathway involving different intracellular locations. The enzyme delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine synthetase was found to be associated with membranes or small organelles. The next enzyme isopenicillin N-synthetase appeared to be a cytosolic enzyme. The enzyme which is involved in the last step of penicillin biosynthesis, acyltransferase, was located in organelles with a diameter of 200-800 nm. These organelles, most probably, are microbodies. A positive correlation was found between the capacity for penicillin production and the number of organelles per cell when comparing different P. chrysogenum strains. PMID- 1899379 TI - Isolation of schistosomin, a neuropeptide which antagonizes gonadotropic hormones in a freshwater snail. AB - The molecular mechanisms underlying parasite-induced inhibitory effects on host reproduction were studied in the freshwater snail, Lymnaea stagnalis, infected with the schistosome parasite Trichobilharzia ocellata. This combination is used as a model system for host-parasite interactions involved in schistosomiasis transmission. The female gonadotropic snail neuropeptide, calfluxin, was labelled with fluorescein isothiocyanate (FITC) and used as a ligand in receptor-binding studies on membranes of its target organ, the albumen gland. The binding of calfluxin to its receptor-guanyl-nucleotide-binding-protein (G-protein) complex was inhibited in vitro in the presence of haemolymph of schistosome-infected snails. This inhibition appeared to be established by a peptidergic factor called schistosomin. The receptor assay was used to identify schistosomin from haemolymph during subsequent purification and characterization steps. The peptide could also be purified from the central nervous systems of non-infected snails, indicating that it is produced by the snail itself and released into the haemolymph as a result of infection. Analysis by plasma-desorption mass spectrometry revealed that purified schistosomin has a molecular mass of 8780 Da. PMID- 1899380 TI - The human dioxin-inducible NAD(P)H: quinone oxidoreductase cDNA-encoded protein expressed in COS-1 cells is identical to diaphorase 4. AB - NAD(P)H: quinone oxidoreductase (NQO1) is believed to be protective against cancer and toxicity caused by exposure to quinones and their metabolic precursors. This enzyme catalyzes the two-electron reduction of compounds, compared with one-electron reduction mediated by NADPH: cytochrome-P450 oxidoreductase which produces toxic and mutagenic free radicals. Recently we cloned and sequenced the cDNA encoding human 2.3,7,8-tetrachlorodibenzo-p-dioxin (dioxin)-inducible cytosolic NQO1 [Jaiswal et al. (1988) J. Biol. Chem. 263, 13572-13578] and provided preliminary evidence that this enzyme may correspond to diaphorase 4, an enzymatic activity present in various tissues that catalyzes the reduction of a variety of quinones by both NADH and NADPH [Edwards et al. (1980) Biochem. J. 187, 429-436]. In the present report we characterize the catalytic properties of the protein encoded by the NQO1 cDNA. The enzyme was synthesized in monkey kidney COS-1 cells transfected with a pMT2-based expression plasmid containing the NQO1 cDNA. Western blot analysis of the transfected cells using an antibody against rat liver cytosolic NQO1 revealed a 31-kDa band that was not detected in nontransfected cells. This band corresponded to a polypeptide with the same electrophoretic mobility as the endogenous NQO1 protein detected in the human hepatoblastoma (Hep-G2) cells with the same antibody. The immunoreactive protein detected in human Hep-G2 cells was induced approximately fourfold by exposure of the cultures to dioxin, an increase commensurate with the increased in quinone oxidoreductase activity. These studies suggest that the protein encoded by NQO1 cDNA is indeed similar, if not identical, to the dioxin-inducible protein band detected in human Hep-G2 cells. Further characterization of the product of NQO1 cDNA, which was present at approximately 20-30-fold higher levels in transfected COS cells than the endogenous product in uninduced human Hep-G2 cells indicated that it had very high capacity (greater than 1000-fold over background) to catalyze the reduction of 2.6-dichloroindophenol and menadione. Besides these two commonly used substrates for quinone reductase, the expressed NQO1 protein also effectively metabolized 2,6-dimethylbenzoquinone, methylene blue, p-benzoquinone, 1,4-naphthoquinone, 2-methyl-1,4-benzoquinone, with the latter being the most potent electron acceptor at 50 microM concentration of the substrate. PMID- 1899381 TI - Linker mutagenesis in the lacZ gene of Escherichia coli yields variants of active beta-galactosidase. AB - Synthetic octameric oligonucleotides that code for a unique restriction site were cloned into a randomly linearized plasmid that carries the lacZ gene. The insertions were mapped by digestion with appropriate restriction endonucleases. 12 mutants were identified which carry an insertion within the lacZ gene and still express active beta-galactosidase. Small deletions or duplications of the wild-type sequence occurred at these positions which restore the correct reading frame. The insertions occurred in the first and the last third of the internal duplication of the lacZ gene and within the domain homologous to dihydrofolate reductase. PMID- 1899383 TI - Submicromolar manganese dependence of Golgi vesicular galactosyltransferase (lactose synthetase). AB - 1. Manganese(II) buffers were set up with inorganic triphosphate, trimethylenediaminetetraacetate and tetramethylenediaminetetraacetate to study the Mn dependence of beta 1,4-galactosyltransferase (lactose synthetase) in preparations of rat mammary gland. 2. In intact particulate preparations, treated with the calcium ionophore A23187, lactose synthesis was abolished by chelators and restored by bivalent transition metal ions in a manner characteristic of activation site I of the pure enzyme. Ni(II) also activated, as did Mg at high concentration. 3. Only Mn(II) could restore endogenous rates, giving an apparent Km of 0.1-0.2 microM, and eliciting about 70% full activity without addition of a site II activator. 4. In purified Golgi membrane vesicles, Mn gave an apparent Km of 0.4 microM. This increased sharply to about 10 microM on permeabilization with filipin, lysis with detergents, solubilization with Triton X-100, or in the pure enzyme. Preparations of chemically undamaged Golgi vesicles, known to include a proportion of the enzyme on exposed membranes, exhibited both low-Km and high-Km components. 5. The response of particulate galactosyltransferase to apparently physiological concentrations of free Mn(II) ion is interpreted as either due to a sensitizing factor within the Golgi lumen, or to the accumulation of Mn at elevated concentrations. Alternatively, the high Km of the soluble enzyme may reflect proteolytic damage. PMID- 1899382 TI - Construction and characterization of a functional chimeric murine-human antibody directed against human fibrin fragment-D dimer. AB - Fibrin-directed monoclonal antibodies may be clinically useful for in vitro thrombus imaging and for the targeting of fibrinolytic agents to blood clots. One such murine monoclonal antibody, (mAb-15C5), raised against the fragment-D dimer epitope of cross-linked human fibrin, was previously characterized [Holvoet, P., Stassen, J. M., Hashimoto, Y., Spriggs, D., Devos, P. & Collen, D. (1989) Thromb. Haemostasis 61, 307-313] has recently been cloned and expressed [Vandamme, A.-M., Bulens, F., Bernar, H., Nelles, L., Lijnen, H. R. & Collen, D. (1990) Eur. J. Biochem. 192, 767-775]. In order to reduce the immunogenicity of the murine mAb 15C5 in man, we have now constructed a murine--human chimera of mAb-15C5, by substituting the cDNA sequences encoding the constant regions of the murine kappa light chain and gamma 1 heavy chain by the corresponding human genomic sequences. Both chimeric murine--human Ig chains were cloned into two separately selectable expression vectors, which were contransfected into Chinese hamster ovary (CHO) cells. Murine--human chimeric mAb-15C5 (mAb-15C5Hu) was purified from the conditioned medium of selected cell lines by chromatography on Zn-chelating Sepharose, protein-A-Sepharose and on insolubilized antigen (fragment-D dimer), with a final yield of 29 micrograms/l and a recovery of 33%. SDS/PAGE without reduction revealed a homogeneous band with a mobility similar to that of natural mAb-15C5, whereas after reduction, both the heavy and the light chains had slightly slower mobilities than their natural counterparts. Expression in the presence of tunicamycin suggested that the differences in gamma 1-chain mobility were due to different N-glycosylation patterns. Immunoblotting of proteins from SDS gels showed immunological reactivity of recombinant mAb-15C5Hu with goat anti (human IgG) IgG and of recombinant and natural murine mAb-15C5 with goat anti (mouse IgG) IgG. Competitive binding revealed a comparable affinity of recombinant murine mAb-15C5, recombinant mAb-15C5Hu and natural mAb-15C5, for fragment-D dimer, indicating that recombinant mAb-15C5Hu was obtained in a functionally intact form. Thus, mAb-15C5Hu may constitute a useful alternative to mAb-15C5 for in vivo use in man. PMID- 1899384 TI - Monoclonal antibodies against various forms of the adenylyl cyclase catalytic subunit and associated proteins. AB - Monoclonal antibodies against partially purified adenylyl cyclase from bovine brain cortex were raised in mice. Three types of antibody were obtained. Type 1 was specific for the calmodulin-sensitive enzyme. Type II also recognized this enzyme, but recognized the calmodulin-insensitive enzymes from a variety of species and tissues as well. Type I antibodies precipitated their antigens in both the native and denatured forms, while type II strongly favored the denatured forms. Type III antibodies precipitated adenylyl cyclase activity, but as shown by Western blot analysis, were directed against 38-kDa and 45-kDa glycoproteins. The 38-kDa protein was identified as synaptophysin. PMID- 1899385 TI - Lymphocytes infected with Theileria parva require both cell-cell contact and growth factor to proliferate. AB - Lymphocytes infected with the intracellular parasite Theileria parva proliferate continuously as lymphoblastoid cell lines. We have previously shown that the continuous proliferation of the T. parva-infected (Tpi) cell line TpM(803) is mediated in part by an autocrine mechanism (Dobbelaere, D. A. E. et al., Proc. Natl. Acad. Sci. USA 1988. 85:4730). We now report that continuous proliferation also requires surface stimulation through cell-cell contact. Under standard culture conditions this surface stimulus is provided by the infected cells themselves, but it can also be provided by uninfected lymphocytes or macrophages. The ability to respond to surface stimulation is critically dependent on the presence of the parasite in the host cell and is lost within 48 h after the elimination of the parasite from the host cell cytoplasm by treatment with the theilericidal drug BW720c. Tpi cells also secrete a growth factor which is able to support the proliferation of diluted Tpi cells. Growth factor secretion is rapidly lost upon elimination of the parasite. Moreover, inhibition experiments using anti-interleukin 2 (IL 2) antibodies show that IL 2 is involved in the proliferation of the Tpi cell lines TpM(803) and IN10. T cell proliferation is dependent on a number of costimulatory signals which are normally provided by accessory cells. The finding that Tpi cells can mutually stimulate each other to grow in the absence of conventional accessory cells helps to explain how they can escape the normal constraints on T cell growth, allowing them to invade and multiply in non-lymphoid as well as lymphoid tissues. PMID- 1899386 TI - Interleukin 4 induces interleukin 6 production by endothelial cells: synergy with interferon-gamma. AB - Interleukin (IL)4 induces IL6 production by human umbilical vein endothelial cells (HUVEC) in a dose-dependent manner, as shown by bioassay and immunoprecipitation. Interferon (IFN)-gamma, which antagonizes IL4 effects on leukocytes, synergized with IL4 in the induction of IL6 production by HUVEC. Contamination with endotoxin was excluded by heat-inactivated IL4, preincubating with anti-IL4 polyclonal antibody and the use of polymyxin B. The presence of IL4 receptors on HUVEC was shown by affinity cross-linking with 125I-IL4, revealing a 110-kDa binding protein. However, compared with the amount seen on T cells the 60 70-kDa cross-linked doublet was present at much lower levels. Additional lower molecular weight cross-linked proteins were isolated only with HUVEC, but the origin of these is unclear. IL6 is a pluripotent cytokine produced by many cells which promotes the differentiation and growth of lymphocytes and the production of acute phase protein by hepatocytes, and is important in the regulation of immunity at the systemic and local levels. Since IL4 and IFN-gamma are produced by T cells, which are frequently associated with vascular endothelium during chronic inflammation, IL4 is likely to be an important cytokine in the regulation of IL6 and perhaps other cytokine production by endothelium in vivo. PMID- 1899387 TI - Normal unstimulated lymphocytes produce granulopoietic inhibitory activity. AB - Normal unstimulated lymphocytes cocultured with normal bone marrow will inhibit day-7 colony- forming units in culture. We have shown that this phenomenon has a molecular basis and attempted to characterize it further. Using specific assays and neutralizing monoclonal antibodies we have found that this granulopoietic inhibitory activity (GIA) is not due to alpha- or gamma-interferon, tumor necrosis factor, or acidic or basic isoferritins. Biochemical studies suggest that it is a glycoprotein with a molecular weight greater than 100,000 daltons. It appears to act on cells in S phase, although it may not be S-phase specific. GIA represents a novel inhibitor that merits further investigation. PMID- 1899388 TI - Examination of elongation factor Tu for aluminum fluoride binding sites using fluorescence and 19F-NMR methodologies. AB - This article reports on a comparison of the interaction of Al3+ and F- with two GTP-binding proteins, elongation factor Tu (EF-Tu) and the hormone sensitive regulatory protein (G protein) G0 alpha. The methodologies chosen to elucidate possible interactions between protein and aluminum fluoride were fluorescence spectroscopy and nuclear magnetic resonance (19F-NMR). Both proteins have tryptophan residues near their nucleotide binding sites, the purported site of aluminum fluoride interaction. It has been assumed for G proteins (including G0 alpha) that aluminum fluoride, in the presence of Mg2+ mimics the magnesium coordinated gamma-phosphate group for the GDP-form of the protein and shifts the protein's conformation toward the active GTP-form. Indeed, changes in intrinsic fluorescence of G0 alpha effected by aluminum fluoride are observed. The presence of aluminum fluoride did not affect the intrinsic fluorescence, spectra or lifetimes, of EF-Tu.GDP 19F-NMR was then used to directly test for bound F-. Fluoride alone or in the presence of either protein gave a single 19F-NMR peak at -10 ppm, characteristic of free F-. With the addition of aluminum to the protein and F- samples a second peak, shifted upfield from the first to -29 ppm, was observed for G0 alpha.GDP. This second peak, which has been assigned to protein bound F-, was not observed for EF-Tu.GDP. These observations show that the interaction of Al3+ and F-, in the presence of Mg2+, may be quite different between the hormone-sensitive G proteins, which bind aluminum fluoride, and the GTP-binding proteins as a whole, which include EF-Tu. Care must therefore be exercised when structural data on the elongation factor, specifically on the nucleotide site, are used to interpret data or compose models intended to describe the hormone-sensitive regulatory G proteins. PMID- 1899389 TI - K+ channel expression in primary cell cultures mediated by vaccinia virus. AB - A recombinant vaccinia virus (VV) was used to express functional Drosophila Shaker H4 K+ channels in primary cell cultures from rat heart (atrial and ventricular myocytes, fibroblasts), autonomic ganglia (SCG neurons) and CNS (hippocampal neurons, cerebral astroglia). In most cells the expressed currents possessed the typical characteristics of the native Drosophila muscle A currents; a few cells showed evidence of hetero-oligomers with new properties. The maximum current density corresponded to a channel density of 2-3/microns 2. Voltage recordings in heart cells showed altered action potential waveforms after successful infection. VV vectors thus are useful for studying altered excitability and cell-specific processing of ion channel proteins. PMID- 1899390 TI - Probing the primary quinone environment in photosynthetic bacterial reaction centers by light-induced FTIR difference spectroscopy. AB - The photoreduction of the primary electron acceptor, QA, has been characterized by light-induced Fourier transform infrared difference spectroscopy for Rb. sphaeroides reaction centers and for Rsp. rubrum and Rp. viridis chromatophores. The samples were treated both with redox compounds, which rapidly reduce the photooxidized primary electron P+, and with inhibitors of electron transfer from QA- to the secondary quinone QB. This approach yields spectra free from P and P+ contributions which makes possible the study of the microenvironment of QA and QA . PMID- 1899391 TI - The role of carbohydrates in vectorial exocytosis. The secretion of the gp 80 glycoprotein complex in a ricin-resistant mutant of MDCK cells. AB - In the polarized epithelial Madin-Darby canine kidney (MDCK) cell line an 80 kDa glycoprotein complex (gp 80) is sorted into the apical pathway of exocytosis and is secreted constitutively at the apical cell surface. The unglycosylated form of the protein complex is secreted in a nonpolar fashion at both surface domains [(1987) J. Cell. Biol. 105, 2735-2743]. Using ricin-resistant MDCK cells the role of the terminal galactose and sialic acid residues in the sorting of the gp 80 complex was analysed. The results suggest that the carbohydrate cores, rather than the ultimate or penultimate sugar residues, play a critical role in the intracellular transport of this protein. PMID- 1899392 TI - A comparative analysis of the cycle fecundity rates associated with combined human menopausal gonadotropin (hMG) and intrauterine insemination (IUI) versus either hMG or IUI alone. AB - Human menopausal gonadotropin (hMG) superovulation combined with washed intrauterine insemination (IUI) has been advocated for the treatment of various forms of infertility when more traditional therapy has failed. To assess the relative efficacy of combined treatment with hMG and IUI compared with either hMG or IUI alone, pregnancy outcomes of the three treatment groups were compared in couples having infertility because of male factor, cervical factor, endometriosis, or unexplained. A total of 751 cycles were analyzed from 322 couples. The mean cycle fecundity rate associated with hMG/IUI therapy was significantly higher than either hMG or IUI therapy alone for all patients (hMG/IUI = 19.6%, hMG = 6.3%, IUI = 3.4%). The improvement in cycle fecundity rates with hMG/IUI therapy was also observed when the couples were separated by infertility diagnostic groups: male factor (hMG/IUI = 15.3%, hMG = 4.4%, IUI = 3.0%), cervical factor (hMG/IUI = 26.3%, hMG = 7.9%, IUI = 5.1%), endometriosis (hMG/IUI = 12.85%, hMG = 6.6%), and unexplained infertility (hMG/IUI = 32.6%, hMG = 5.5%, IUI = 0%). Moreover, in patients who had failed to conceive with hMG or IUI alone, the cycle fecundity rate when they were switched to hMG/IUI therapy equaled that of patients who received combined therapy from the onset. We conclude that cycle fecundity rates and cumulative pregnancy rates are significantly greater using a combination of hMG and IUI compared with either modality alone in the treatment of male factor, cervical factor, endometriosis, or unexplained infertility. Indeed, in couples with nontubal related infertility, cycle fecundity rates with hMG/IUI approach the rates seen with in vitro fertilization and gamete intrafallopian tube transfer. PMID- 1899393 TI - Pregnancy rates after timed intercourse or intrauterine insemination after human menopausal gonadotropin stimulation of normal ovulatory cycles: a controlled study. AB - Forty-eight patients with male (n = 16) or idiopathic (n = 32) infertility were stimulated with human menopausal gonadotropin. Intrauterine insemination (IUI) or natural intercourse were performed after either human chorionic gonadotropin (hCG)-induced or spontaneous, urinary luteinizing hormone (LH) surge-monitored ovulation. A total of 148 cycles were analyzed. In 40 cycles treated with hCG induced ovulation and IUI, 3 (7.5%) patients conceived, whereas 37 women accomplished natural intercourse after hCG-induced ovulation and 2 (5.5%) became pregnant. When inseminated after a spontaneous LH surge, 3 (8.8%) of 34 patients achieved a pregnancy; no conception occurred in 37 spontaneously ovulatory cycles combined with timed intercourse. Pregnancy rates did not substantially differ between the treatment modalities or between mono-ovulatory and polyovulatory cycles. The cycle characteristics between spontaneous ovulatory and hCG-induced cycles significantly did differ. PMID- 1899394 TI - Gamete intrafallopian transfer: assessment of the optimal number of oocytes to transfer. AB - The optimum number of oocytes that should be transferred at the time of gamete intrafallopian transfer (GIFT) is important information. Nonessential oocytes can be inseminated and frozen for later use or the extra oocytes can be donated to another women. In this preliminary study, the results of 399 consecutive GIFT procedures were evaluated retrospectively as a function of the number of oocytes transferred. Women who received four or more oocytes were three times more likely to achieve a clinical pregnancy than those who received three or less. There was no statistically significant difference in pregnancy rates between patients who received five, six, seven, or eight oocytes. Oocytes in excess of five may be more effectively used if they are fertilized and frozen as embryos for later transfer rather than replacing them all at the time of GIFT. PMID- 1899395 TI - Failure of oocyte retrieval during in vitro fertilization: a sporadic event rather than a syndrome. AB - Failure to retrieve oocytes during in vitro fertilization (IVF) treatment was recently referred to as the "empty follicle syndrome." Data on the possible repetitiveness of this during previous or subsequent IVF attempts is lacking, which limits the understanding of its significance to the involved patients. Of 26 patients who had cycles during which no oocytes were retrieved, 10 were pregnant in the past and 20 had at least one other IVF cycle that yielded oocytes. There was no difference in the frequency of any stimulation protocol among the failure cycles compared with the successful ones. Hormonal response pattern and the number of large follicles observed sonographically did not differ between the two occasions. Fertilization occurred in 70% of the successful cycles and two biochemical pregnancies were recorded. In 13 patients, at least one cycle was canceled because of poor ovarian response, but 9 of these 13 had at least one other successful cycle. We conclude that the so-called empty follicle syndrome cannot be predicted by the pattern of ovarian response and does not predict a reduced fertility potential in future cycles. PMID- 1899396 TI - Stimulation of endogenous surge of luteinizing hormone with gonadotropin releasing hormone analog after ovarian stimulation for in vitro fertilization. AB - The effect of induction of preovulatory endogenous surge of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) with intranasal administration of GnRH-analog (GnRH-a) in an in vitro fertilization (IVF) program is reported. The use of GnRH-a resulted in a significantly better percentage of replaceable embryos (91% versus 85%). The pregnancy rate was 51% in comparison with 32% in control cycles in which follicular maturation was achieved by human chorionic gonadotropin administration. There was no significant difference in the postoocyte recovery serum progesterone patterns between the two groups. Our results indicate that the induction of endogenous LH and FSH surge with GnRH-a may be successfully employed for final follicular maturation after ovarian suprastimulation without affecting the outcome of IVF adversely. Apart from being a more physiological approach to oocyte maturation, it also has potential economic and clinical advantages. PMID- 1899397 TI - Effects of chronic bromocriptine-induced hypoprolactinemia on plasma testosterone responses to human chorionic gonadotropin stimulation in normal men. AB - To study the role played by normal levels of plasma prolactin (PRL) in the secretion of testosterone (T) in the testes, we induced hypoprolactinemia with a daily dose of 5 mg bromocriptine administered orally in five normal men 20 to 35 years of age for 8 weeks. The basal PRL, T, luteinizing hormone, follicle stimulating hormone, and maximum responses of plasma T to human chorionic gonadotropin (hCG) stimulation were measured every 2 weeks. Basal levels of plasma T were reduced in the 1st 2-week-long period of hypoprolactinemia. In the 4-week-long period of hypoprolactinemia, the maximal response of plasma T to hCG stimulation was significantly reduced. The findings suggest that normal levels of plasma PRL may play an important role in the secretion of T in the human testes in vivo. PMID- 1899398 TI - Evidence for altered receptor-binding activity of serum follicle-stimulating hormone in male infertility. AB - It is generally assumed that the immunological activity of the follicle stimulating hormone (FSH) molecule, as reported in the radioimmunoassay (RIA), is identical to the molecule's biological activity. To test the validity of this assumption, the receptor-binding and immunological activities of FSH in the serum of 35 infertile males and 11 fertile males were determined by radioreceptor assay (RRA) and by the standard RIA. The results were analyzed in terms of the ratio of binding (RRA) to immunological (RIA) activity x 100%, referred to as the B/I%, for each patient based on data from the RRA and RIA, respectively. The B/I% for fertile men ranged from 44% to 113% (mean of 80%). In the group of 11 infertile men with normal FSH levels by RIA (50 to 300 ng/mL), there was no significant difference in B/I% (range of 27% to 99%, mean of 59%) from the fertile controls. However, a statistically significant decrease in B/I% (range of 7% to 35%, mean of 18%) was noted in the 24 hypergonadotropic infertile men with RIA levels of serum FSH greater than 300 ng/mL. These significant discrepancies between receptor-binding and immunological activities of serum FSH raise the question of whether RIAs alone are valid parameters for the endocrine evaluation of infertile men with elevated serum FSH levels. PMID- 1899399 TI - Comparison of the indirect immunobead, radiolabeled, and immunofluorescence assays for immunoglobulin G serum antibodies to human sperm. AB - The relative sensitivities of the indirect immunobead test, the indirect flo cytometric immunofluorescence assay, and an indirect radiolabeled antiglobulin assay were compared. Eighteen immunobead test positive sera and 18 negative sera were used as the standard for the other two assays. Of the 18 positive sera, 14 (77%) and 5 (27%) were positive in the immunofluorescence assay and the radiolabeled antiglobulin assay, respectively. Four (22%) of the low titer immunobead test positive sera were negative by both the immunofluorescence assay and the radiolabeled antiglobulin assay. However, there was a significant positive correlation between the results of the immunofluorescence assay and the radiolabeled antiglobulin assay (r = 0.73) and between the results of the radiolabeled antiglobulin assay and the titer of the immunobead test (r = 0.82). The use of an unselected sperm population in the radiolabeled antiglobulin assay and the classical indirect immunofluorescence method using methanol-fixed sperm gave false-positive results in the radiolabeled antiglobulin assay and the immunofluorescence assay. These results suggested that immunoglobulin G antisperm antibody positive sera may be reactive both to sperm surface and internalized sperm antigens. PMID- 1899400 TI - Gonadotropin-releasing hormone agonist (leuprolide acetate) induced ovarian hyperstimulation syndrome in a woman undergoing intermittent hemodialysis. AB - Moderate ovarian hyperstimulation syndrome occurred after LA was administered to control menorrhagia in an anephric woman who required hemodialysis. We postulate that women who require dialysis may be at special risk for the development of this syndrome. PMID- 1899401 TI - Trans-Atlantic in vitro fertilization cold war. PMID- 1899402 TI - Reproductive roulette--prognosis for ovarian failure. PMID- 1899403 TI - Evidence for the involvement of a pertussis toxin-insensitive G-protein in egg activation of the frog, Xenopus laevis. AB - Activation responses of the frog egg at fertilization include the release of calcium from intracellular stores and the opening of calcium-dependent chloride channels, which produce the fertilization potential. To investigate the presence of guanine nucleotide-binding proteins (G-proteins), and their role in initiation of these events in the egg of the frog Xenopus laevis, we assayed for pertussis and cholera toxin substrates, and applied activators and inhibitors of G proteins. Pertussis toxin catalyzed the [32P]ADP ribosylation of a Mr 40,000 component, but no cholera toxin substrates were demonstrated. Injection of greater than or equal to 25 pmole of guanosine-5'-O-(3-thiotriphosphate) GTP gamma-S), an activator of G-proteins, produced a change in membrane potential that mimicked the fertilization potential and also caused cortical granule exocytosis and cortical contraction. Injections of up to 600 pmole of guanosine 3':5'-cyclic monophosphate or 9 nmole of guanosine-5'-(beta-gamma imido)triphosphate did not active eggs. The membrane potential response to GTP gamma-S injection showed the same peak and chloride dependence as the fertilization potential, although the duration of the GTP-gamma-S response was somewhat greater. GTP-gamma-S did not activate eggs if the calcium rise was prevented by prior injection of the calcium chelator BAPTA. Injection of up to 200 ng of cholera toxin did not activate eggs. However, eggs were activated by applying 1 nM serotonin to eggs that had been injected with a specific mRNA for the serotonin 1c receptor, a member of the class of receptors that act by way of G-proteins. Egg activation in response to either sperm or serotonin was not inhibited by pertussis toxin, under experimental conditions where approximately 80-90% of the toxin substrate was ADP-ribosylated. These results support the hypothesis that sperm activate Xenopus eggs at fertilization by way of a pertussis and cholera toxin-insensitive G-protein. PMID- 1899404 TI - The expression of intracisternal A particle genes in the preimplantation mouse embryo. AB - Intracisternal A particles (IAP), murine endogenous retrovirus, make up 0.3% of the mouse genome. They are expressed in some normal tissues, certain transformed cell lines, and show stage-specific patterns of expression in early embryos. We have used peptide-specific antisera and the polymerase chain reaction to explore type-specific expression of these IAP during preimplantation development. In this paper we show that the IAP core protein, p73, characteristic of type IIAP, is present throughout preimplantation development while the gag-pol fusion protein p120, characteristic of the variant type I delta 1, is synthesized and expressed only from the 8-cell stage onward. Type IIAP RNA is present at all stages and appearance of p120 at the 8-cell stage could represent new transcription or translation from a preexisting I delta 1 message. The presence of type II IAP RNA varies according to stage, with two sizes of type II transcripts present at all stages except the 2-cell stage at which time only the smaller of the two transcripts can be detected. The reappearance of the larger type II transcript subsequent to the 2-cell stage implies new transcription of this type II subspecies. The presence of type I, II, and p73 in the unfertilized egg strongly suggests maternal inheritance from the oocyte. PMID- 1899405 TI - Hyaluronan-dependent pericellular coats of chick embryo limb mesodermal cells: induction by basic fibroblast growth factor. AB - Basic fibroblast growth factor (FGF) has been shown previously to be present in the chick embryonic limb during early stages of its development, at which time the limb mesodermal cells are proliferating within a hyaluronan-rich extracellular matrix. In this study, basic FGF was found to stimulate hyaluronan synthesis and production of hyaluronan-dependent pericellular coats by mesodermal cells from the chick embryo limb; acidic FGF, platelet-derived growth factor, epidermal growth factor, and retinoic acid either had a much smaller effect than basic FGF or an inhibitory effect. Transforming growth factor-beta stimulated hyaluronan synthesis and coat formation but, unlike basic FGF, this factor also stimulated chondroitin sulfate production by the mesodermal cells. PMID- 1899406 TI - Effect of diabetes and aging on carboxymethyllysine levels in human urine. AB - Carboxymethyllysine (CML) has been identified as a modified amino acid that accumulates with age in human lens proteins and collagen. CML may be formed by oxidation of fructoselysine (FL), the Amadori adduct formed on nonenzymatic glycosylation of lysine residues in protein, or by reaction of ascorbate with protein under autoxidizing conditions. We proposed that measurements of tissue and urinary CML may be useful as indices of oxidative stress or damage to proteins in vivo. To determine the extent to which oxidation of nonenzymatically glycosylated proteins contributes to urinary CML, we measured the urinary concentrations of FL and CML in diabetic (n = 26) and control (n = 28) patients. The urinary concentration of FL correlated strongly with HbA1 measurements and was significantly higher in diabetic compared with control samples (9.2 +/- 6.5 and 4.0 +/- 2.8 micrograms/mg creatinine, respectively; P less than 0.0001). There was also a strong correlation between the concentrations of CML and FL in both diabetic and control urine (r = 0.67, P less than 0.0001) but only a weakly significant increase in the CML concentration in diabetic compared with control urine (1.2 +/- 0.5 and 1.0 +/- 0.3 micrograms/mg creatinine, respectively; P = 0.05). The molar ratio of CML to FL was significantly lower in diabetic compared with control patients (0.25 +/- 0.12 and 0.43 +/- 0.16, respectively; P less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1899407 TI - Influence of environmental viral agents on frequency and tempo of diabetes mellitus in BB/Wor rats. AB - Elimination of environmental viruses by cesarean derivation of the University of Massachusetts colony of BB/Wor rats increased the frequency and accelerated the tempo of spontaneous diabetes among diabetes-prone (DP) rats. In contrast, the viral-antibody-free (VAF) environment did not alter the resistance of pre-VAF diabetes-resistant (DR) rats to spontaneous and RT6+ T-lymphocyte-depletion induced diabetes. Pre-VAF and VAF rats have essentially the same lymphocyte subsets, and VAF-DP rats are susceptible to the adoptive transfer of diabetes and to the diabetes-accelerating effects of polyinosinic-polycytidylic acid injections. These results suggest that the presence of environmental viral pathogens may act to inhibit effector cell function in lymphopenic DP rats while enhancing effector cell activity in nonlymphopenic DR rats. PMID- 1899408 TI - Do non-steroidal anti-inflammatory drugs increase colonic permeability? AB - Urinary excretion of orally administered lactulose and 51 chromium labelled ethylenediamine tetra-acetate (51Cr-EDTA) was measured in 12 healthy adult subjects and in six patients with ileostomies to assess intestinal permeability. In normal subjects, 24 hour urinary recovery of 51Cr-EDTA was significantly greater than that of lactulose (mean (SEM) 2.27 (0.15) v 0.50 (0.08)% oral dose; p less than 0.001), but in ileostomy patients recovery of the two markers was the same. In normal subjects, therefore, the difference between the two markers may arise from bacterial break-down of lactulose but not of 51Cr-EDTA in the distal bowel, urinary excretion of lactulose representing small intestinal permeation and that of 51Cr-EDTA representing both small and large intestinal permeation. The markers were then given simultaneously to nine patients receiving non steroidal anti-inflammatory drugs (NSAIDs) for rheumatoid arthritis and osteoarthritis. The 24 hour urinary recovery of 51Cr-EDTA in the patients was significantly greater than normal (4.64 (1.20) v 2.27 (0.15)% oral dose; p less than 0.01), but that of lactulose was not significantly affected. Moreover, the increase in 51Cr-EDTA recovery was most noticeable in the later urine collections. Both of these findings suggest that NSAIDs may increase colonic permeability. PMID- 1899410 TI - The effect of owning private long-term care insurance policies on out-of-pocket costs. AB - This article examines the effect of owning long-term care insurance policies on the amount of out-of-pocket costs incurred by the elderly during their nursing home stays, and the importance of different policy features and restrictions. Data were drawn from the 1985 National Nursing Home Survey, and from copies of long-term care insurance policies collected from 11 leading companies during the spring and summer of 1988. The study results show a great deal of uncertainty concerning amounts the policies are likely to pay toward nursing home stays. This implies that the policies collected did not adequately fulfill one of the primary purposes of insurance: a reduction in risk and uncertainty. To examine whether rapid policy changes in recent years have made a difference, we assessed each of seven policy features and found that the two most important restrictions in long term care insurance policies are prior hospitalization and level-of-care requirements. Recently, the National Association of Insurance Commissioners (NAIC) recommended that states prohibit the sale of policies containing these restrictions. Our findings confirm the wisdom of this recommendation. We did find, however, that two other policy restrictions--policy maximums and lack of inflation adjustment--are problematic. We recommend that the NAIC expand its model regulations to require that policy maximums be a minimum of four years, and that some form of inflation protection be incorporated into policy benefit structures. PMID- 1899409 TI - Determinants of recurrent ischaemia and revascularisation procedures after thrombolysis with recombinant tissue plasminogen activator in primary coronary occlusion. AB - This paper reports the immediate effects of thrombolysis and their subsequent influence on revascularisation procedures and clinical outcome over the subsequent twelve months. Coronary arteriography was performed at 21 days on 131 of 145 patients who received recombinant tissue plasminogen activator (n = 68) or placebo (n = 63) within 2.5 hours of symptom onset after primary coronary occlusion. Patency rates (TIMI grades 2 and 3) of the infarct-related artery were 81% with plasminogen activator and 63% with placebo (P = 0.02). Early (within 21 days) angiography for recurrent ischaemia was necessary in 31 (21%) patients (20 plasminogen activator, 11 placebo NS) and definite reinfarction occurred in 8 (5%) patients (4 plasminogen activator, 4 placebo). During one year follow-up without planned secondary intervention, coronary artery bypass grafting was more frequent in patients who had received thrombolytic therapy (23% plasminogen activator, 4% placebo P = 0.001); coronary angioplasty procedures were similar in both groups (12% plasminogen activator, 11% placebo NS). Mortality at 21 days was 5% (4 plasminogen activator, 4 placebo) and at one year was 7% (5 plasminogen activator, 5 placebo). Logistic regression analysis identified models comprising characteristics predictive of subsequent bypass grafting (plasminogen activator, multivessel disease, occluded infarct-related artery) and coronary angioplasty (non-q wave infarction, severe (91-99%) residual stenosis, left anterior descending infarct-related artery). Initial non-q wave infarction was the only predictor of early recurrent ischemia (odds ratio 4, P = 0.02) irrespective of residual stenosis severity. PMID- 1899413 TI - Radiosensitizing and cytotoxic properties of mitomycin C in a C3H mouse mammary carcinoma in vivo. AB - The radiosensitizing and cytotoxic properties of Mitomycin C (MMC) was investigated in vivo using regrowth delay and tumor control assays. MMC significantly enhanced the radiation-induced growth delay when administered 15 min before irradiation; the slope of the dose response curve significantly increased and corresponded to a Dose Modifying Factor (DMF) of 1.9 (1.5-2.3; p less than 0.001). When MMC was given 4 hr after irradiation, the additional regrowth delay resulted in a parallel shift of the dose response curve, and MMC was not significantly dose modifying (DMF 1.3 (0.9-1.3); p less than 0.05). From isobologram analysis it was found that the preirradiation MMC schedule resulted in supra-additive responses, whereas MMC given after irradiation had an additive effect. The enhancement of radiation-induced tumor control was similarly found to peak when MMC was given 6 hr to 15 min prior to irradiation. At these intervals, the observed TCD50 for the combined treatments relative to radiation alone corresponded to Enhancement Ratios of 1.27 and 1.29, respectively (p less than 0.001). Longer intervals between the modalities reduced the enhancement, but the combined treatments were still significantly better than radiation alone (ER 1.12, 1.16 and 1.17; p less than 0.001). The significant enhancement of tumor control correlated with a substantial drug-induced cytotoxic effect toward hypoxic tumor cells, as determined by clamped TCD50 experiments. A single dose of MMC (3 mg/kg) was found to kill up to 97% of all hypoxic tumor cells. PMID- 1899411 TI - Combined modality treatment of advanced cancers of the oral cavity and oropharynx. AB - From May 1985 to June 1988, 70 evaluable patients with advanced squamous cell cancers of the oral cavity and the oropharynx were treated with preoperative combined radio-chemotherapy. Treatment consisted of 50 Gy/25 fractions/5 weeks, combined with concomitant administration of mitomycin C on day 1 (15 mg/m2, i.v. bolus) and 5-fluorouracil during the first 5 days of irradiation (750 mg/m2/24 hours, continuous infusion). Surgery was performed 3 to 5 weeks following irradiation. Treatment tolerance was good and local mucosal reaction was increased, but no major systemic side effects were recorded. At surgery, 3-5 weeks following irradiation, 48.6% of the operation specimens did not contain any histologically detectable residual tumor. Overall survival is 61%, being 69% in T2 and T3, while none of the patients with bone invasion has survived. Median survival is 28, 26, and 9 months in T2, T3 and T4 stages, respectively. Loco regional relapses have been recorded in 33% of the patients, occurring in 27% of T2, 25% of T3, and 88% of T4 stages. Patients have been spared mutilating radical neck dissection because of combined presurgical treatment without impaired survival or loco-regional relapse rate. PMID- 1899412 TI - Effect of host age on microenvironmental heterogeneity and efficacy of combined modality therapy in solid tumors. AB - The implications of microenvironmental heterogeneity in solid tumors for combined modality therapy were assessed by comparing the microenvironmental profiles and therapeutic responses of EMT6 tumors implanted into young and aging mice. The radiobiological hypoxic fraction of tumors in aging mice was shown to be 41% (95% CL, 28-60%), while that in young adult hosts is 19% (95% CL, 14-25%). These microenvironmental differences were also seen in perfusion studies and in studies of the intratumoral pH and pO2 in young and aging mice. The therapeutic importance of microenvironmental factors can be examined in this system, as the tumor cells per se are identical, but the proportions of tumor cells in adverse microenvironments are different. Studies described here show that mitomycin C, an agent with selective toxicity to hypoxic cells, produced greater antineoplastic effects in tumors in aging mice when used alone or as an adjunct to radiation. Combined-modality regimens incorporating agents selectively toxic to hypoxic cells may be especially valuable in improving the results of radiotherapy in tumors in which the tumor-host interactions have resulted in unusually large hypoxic fractions. PMID- 1899414 TI - Localization of the Mycoplasma pneumoniae cytadherence-accessory proteins HMW1 and HMW4 in the cytoskeletonlike Triton shell. AB - The location of the cytadherence-accessory high-molecular weight proteins 1 and 4 (HMW1/4) within Mycoplasma pneumoniae cells has been studied by both biochemical and electron microscopic techniques. Peptide mapping studies demonstrated that HMW1/4 share almost identical peptide profiles, suggesting that the two proteins are structurally related. Examination of thin sections of M. pneumoniae with antibodies to HMW1/4 and colloidal gold particles revealed distinct labeling of the filamentous extensions of the mycoplasma cells. Labeling was absent on thin sections of a cytadherence-deficient variant lacking HMW1/4. HMW1/4 partitioned in the detergent-insoluble fraction following Triton X-100 extraction, and analysis by sucrose density gradient centrifugation suggested that HMW1/4 are part of a high-molecular-weight, multiprotein complex. These results were confirmed by immunogold labeling of Triton X-100-extracted M. pneumoniae cells incubated with antibodies to HMW1/4: gold particles bound in specific clusters to detergent-insoluble filaments. Finally, immunogold labeling of whole cells revealed that HMW1/4 are exposed on the cell surface, although to a lesser degree than on the cell interior. These findings indicate that HMW1/4 are membrane proteins associated with the cytoskeletonlike triton shell of M. pneumoniae and localized primarily in the filamentous extensions of the mycoplasma cells. PMID- 1899415 TI - Effects of structural changes in the dsdA-dsdC intergenic region on D-serine deaminase synthesis. AB - Single-base-pair changes well upstream of its transcription initiation site resulted in partially to fully constitutive expression of the D-serine deaminase structural gene, dsdA, independently of the cyclic AMP-cyclic AMP-binding protein complex and of the specific D-serine deaminase activator protein. These promoter mutations appear to define a consensus sequence that is repeated several times. Basal expression of dsdA+ was also strongly enhanced by subcloning on multicopy plasmids, by the DNA gyrase inhibitor novobiocin, and in dsdC(Con) mutants by increasing growth temperature. These results suggest that activation of dsdA+ expression by the dsdC-encoded protein involves distortion of promoter DNA. A dsdA translation start at bp -731 was verified by subcloning of dsdC+. Plasmid specified activator at a high concentration interfered with chromosomal dsdC(Con) expression, and the interference was enhanced by deletion of most of the intergenic region from the plasmid. Even at a high concentration, however, plasmid-specified activator did not activate expression of chromosomal dsdA+, and in one case it was actually repressive. These results confirm the strong cis tropism of plasmid-specified dsdC-encoded protein and suggest that it is mediated by multiple sites in the dsdA-dsdC intergenic region. PMID- 1899417 TI - Ambulatory monitoring of blood pressure. AB - When ambulatory monitoring results differ from office values it is very likely that the ambulatory readings more accurately reflect patient status. Thus, a determination of 24-hour antihypertensive control and comparison of the efficacy of drug regimens can help to prevent undertreatment as well as overtreatment. PMID- 1899418 TI - Problems of polypharmacy and intercurrent disease. AB - Preventing lethal sequelae rather than simply controlling blood pressure is the major goal of antihypertensive treatment. By that criterion, there is reason to question the efficacy of current stepped-care protocols. Alternate approaches that incorporate concerns about both intercurrent disease conditions and their multidrug demands are critically examined. PMID- 1899419 TI - Managing the problem patient. AB - Anxiety, overtreatment, inappropriate combination therapy, and noncompliance are all characterized as prevalent etiologic factors in so-called resistant hypertension. But perhaps the most common problem that expresses itself as resistant hypertension is failure to adequately control intravascular volume. The key point is that a cause for resistance is almost always discoverable. PMID- 1899416 TI - The role of integrins in the maintenance of endothelial monolayer integrity. AB - This paper shows that, in confluent human umbilical vein endothelial cell (EC) monolayers, the integrin heterodimers alpha 2 beta 1 and alpha 5 beta 1, but not other members of the beta 1 subfamily, are located at cell-cell contact borders and not at cellular free edges. Also the alpha v chain, but not its most common partner beta 3, that is widely expressed in EC cell-matrix junctions, is found at cell-cell borders. In EC monolayers, the putative ligands of alpha 2 beta 1 and alpha 5 beta 1 receptors, i.e., laminin, collagen type IV, and fibronectin, are also organized in strands corresponding to cell-cell borders. The location of the above integrin receptors is not an artifact of in vitro culture since it has been noted also in explanted islets of the native umbilical vein endothelium. The integrins alpha 2 beta 1 and alpha 5 beta 1 play a role in the maintenance of endothelial monolayer continuity in vitro. Indeed, specific antibodies to alpha 2 beta 1, alpha 5 beta 1, and the synthetic peptide GRGDSP alter its continuity without any initial cell detachment. Moreover, antibodies to alpha 5 beta 1 increase the permeation of macromolecules across confluent EC monolayers. In contrast beta 3 antibodies were ineffective. It is suggested that the relocation of integrins to cell-cell borders is a feature of cells programmed to form polarized monolayers since integrins have a different distribution in nonpolar confluent dermal fibroblasts. The conclusion is that some members of the integrin superfamily collaborate with other intercellular molecules to form lateral junctions and to control both the monolayer integrity and the permeability properties of the vascular endothelial lining. This also suggest that integrins are adhesion molecules provided with a unique biochemical adaptability to different biological functions. PMID- 1899420 TI - Obstacles to the control of hypertension. PMID- 1899421 TI - Pulsatile secretion of luteinizing hormone and prolactin in lactating and nonlactating women and the response to naltrexone. AB - To investigate the mechanisms responsible for the postpartum suppression of reproductive function, LH and PRL levels were determined at 10-min intervals for 8 h in 10 lactating women, in 10 nonlactating women treated with bromocriptine, and in 5 nonpuerperal women. The lactating women were studied on postpartum day 7 (n = 5) or between days 28 and 35 (n = 5). All nonlactating women were studied on day 7. Five of them were treated with the opioid antagonist naltrexone to evaluate the role of endogenous opioids. By using a specific LH assay which does not cross-react with hCG, we were able to measure pulsatile LH secretion in the early puerperium for the first time. On day 7, LH levels were below the detection limit in both lactating and nonlactating women, hence no pulses could be detected. Chronic opioid blockade in bromocriptine-treated non-lactating women did not result in increased LH levels. Pulsatile LH secretion was present between days 28 and 35 of lactation, although pulse amplitude (P less than 0.05) and mean LH level (P less than 0.05) were lower than in nonpuerperal women. Mean LH in lactating women was negatively correlated with mean PRL (-0.87, P less than 0.05). Deconvolution analysis of the PRL responses to suckling revealed that PRL was secreted in distinct bursts, separated by intervals of secretory quiescence. Mean duration of PRL bursts was 40 +/- 4 min and the maximum secretory rate was reached around the end of suckling. We conclude that pulsatile LH secretion is completely suppressed during early lactation and partially suppressed during late lactation. Because the duration of suckling was similar, the relatively strong suppression during the early puerperium must be due to additional inhibitory factors. It has been suggested that endogenous opioids are involved in this process, but our results in puerperal women do not support this hypothesis. PMID- 1899422 TI - Contrasting effects of various potassium salts on renal citrate excretion. AB - Mechanisms for the citraturic response to potassium citrate treatment were sought by assessing renal citrate clearance and acid-base status after oral administration of potassium citrate, potassium bicarbonate, and potassium chloride. After 2 weeks of treatment of eight patients with stones at a dose of 80 meq/day, urinary citrate rose significantly from 2.5 +/- 1.6 mmol/day (no drug) to 5.1 +/- 1.7 mmol/day with potassium citrate and to 4.5 +/- 1.5 mmol/day with potassium bicarbonate (P less than 0.05), but did not change significantly with potassium chloride. Citrate clearance increased from 8.0 to 27.4 mL/min with potassium citrate and 25.8 mL/min with potassium bicarbonate (P less than 0.05), but did not increase with potassium chloride. Both potassium citrate and potassium bicarbonate significantly raised urinary bicarbonate and decreased urinary ammonium, titratable acid, and net acid excretion. Potassium chloride was without effect. Effects of potassium citrate on urinary citrate, citrate clearance, and acid-base status tended to be more prominent than those of potassium bicarbonate, but these changes were not significant. Thus, the citraturic action of potassium citrate is largely accountable for by provision of an alkali load. Potassium itself had no effect in the absence of potassium deficiency. PMID- 1899423 TI - Endurance training decreases serum testosterone levels in men without change in luteinizing hormone pulsatile release. AB - Cross-sectional studies have suggested that total and bioavailable testosterone levels are reduced in some male athletes. Such changes may be related to loss of body weight, increased serum cortisol, and/or alterations in LH pulsatile release. To determine how endurance training may affect androgen levels, we measured serum total testosterone, sex hormone-binding globulin, free androgen index, LH, FSH, PRL, cortisol, and weight in 15 previously sedentary males. We also examined pulsatile LH release in a subset of 5 subjects. Over 6 months of training, the men increased weekly running mileage to an average of 56 km/week. Total testosterone and free androgen index levels decreased significantly. PRL and cortisol also decreased, while single sample LH and FSH remained unchanged. There was a significant reduction in weight, which did not correlate with changes in serum testosterone levels. LH pulsatile release was not altered by training in the subset of 5 runners. These data confirm previous findings of physiological reduction in serum testosterone and PRL levels and suggest that the testosterone decrease is not related to changes in LH pulsatile release, weight, or increased serum cortisol levels. PMID- 1899424 TI - Inhibin and activin modulate human monocyte chemotaxis and human lymphocyte interferon-gamma production. AB - Inhibin and activin are referred to as gonadal glycoprotein hormones whose function is the control of FSH release from the pituitary gland. However, several observations indicate that inhibin and activin are produced in various organs and serve multiple functions. Because bone marrow and spleen produce inhibin and activin, our aim was to evaluate their possible effect on cell-mediated immune function. For this reason we studied 1) monocyte chemotaxis, 2) lymphocyte interferon-gamma production, 3) phytohemagglutinin-induced lymphocyte proliferation, and 4) nonmajor histocompatibility complex-restricted and lymphokine-activated lymphocyte cytotoxicity. All studies were performed on human peripheral blood cells in the absence or presence of various doses of inhibin, activin, or inhibin plus activin. A significant dose-related increase in monocyte chemotaxis was induced by inhibin. Activin increased the migrational activity of monocytes, but via random, not directed, migration. Inhibin significantly decreased interferon-gamma production, and its effect was reversed by activin. Inhibin and/or activin had no significant effect on either phytohemagglutinin induced lymphocyte proliferation or lymphocyte cytotoxic capability. The present demonstration that inhibin and activin may affect some immune parameters suggests a possible involvement of these hormones in regulating cell-mediated immune function. PMID- 1899425 TI - Erythrocyte carbonic anhydrase-I concentrations in patients with Graves' disease and subacute thyroiditis reflect integrated thyroid hormone levels over the previous few months. AB - We have recently reported that in patients with hyperthyroidism, red blood cell (RBC) zinc (Zn), most of which is present as the metal of carbonic anhydrase-I isozyme (CAI), reflects a patient's integrated thyroid hormone level over the previous few months. In the present report the RBC CAI concentration was measured by RIA in 26 healthy controls, 25 patients with hyperthyroid Graves' disease, 5 patients with primary hypothyroidism, and 10 subjects with subacute thyroiditis with elevated thyroid hormone levels. The mean (+/- SD) RBC CAI concentration in euthyroid controls was 380 +/- 70 nmol/g hemoglobin (Hb), and the normal range defined as the mean +/- 2 SD, was 240-520 nmol/g Hb. The mean RBC CAI in Graves' disease was decreased (180 +/- 53 nmol/g Hb), and 22 patients (88%) had subnormal values. The mean RBC CAI concentrations in hypothyroidism and subacute thyroiditis were not different from the control values. After treatment with antithyroid drugs, both mean the plasma T4 and T3 levels in 11 Graves' patients became normal within 4 weeks, but the normalization of RBC CAI lagged behind by about 2 months. Furthermore, the highest correlation was observed between the RBC CAI and plasma T4 and T3 levels measured 8 weeks earlier. During prednisolone therapy the RBC CAI in patients with subacute thyroiditis remained at a normal level. These results suggest that 1) not only RBC Zn but also the RBC CAI concentration in patients with Graves' disease reflect the patient's mean thyroid hormone level over the preceding several months; and 2) in patients with subacute thyroiditis, elevation of plasma thyroid hormone concentrations is transient and causes little change in the RBC CAI concentration. PMID- 1899426 TI - Interferon-gamma inhibition suppresses experimental allergic neuritis: modulation of major histocompatibility complex expression of Schwann cells in vitro. AB - This study examines the modulation of major histocompatibility complex (MHC) expression on Lewis rat Schwann cells (Scs) cultured in the presence of dorsal root ganglion neurons (DRG). MHC class I and II molecules were induced on Scs using recombinant murine interferon-gamma (IFN-gamma), lymph node cells (LNC), removed at day 9 from Lewis rats with experimental allergic neuritis (EAN) and syngeneic T-cell line cells responsive to P2 basic protein. EAN LNC induced MHC class I on Scs but only IFN-gamma or P2-responsive T-cells induced MHC class II. Control LNC from animals injected with Freund's adjuvant alone or naive spleen cells did not induce MHC class II. P2 T-cells clustered in aggregates to the Scs. Similar studies were performed with inhibitors of IFN-gamma; hydrocortisone, cyclosporin A, dibutyryl cyclic AMP, methyl-xanthine and prostaglandin E2. Each agent produced a dose-dependent inhibition of MHC expression and prevented clustering of P2-responsive T-cells to Scs. PMID- 1899427 TI - Enhanced production of neutrophil-activating peptide-1/interleukin-8 in rheumatoid arthritis. AB - Production of the neutrophil-activating peptide (NAP)-1/IL-8 by mononuclear phagocytes from patients with RA and from control subjects was studied under various conditions. Mononuclear cells from bone marrow (BMMC), PBMC, and synovial fluid (SFMC) were cultured for up to 48 h in the absence or presence of Escherichia coli LPS, different interleukins, interferon-gamma, zymosan, or immune complexes, and the neutrophil-stimulating activity released into the culture medium was determined. As shown by neutralization with an antiserum raised against human recombinant NAP-1/IL-8, over 90% of this activity could be attributed to NAP-1/IL-8. In unstimulated mononuclear cells from control individuals and BMMC from RA patients, the production of NAP-1/IL-8 was very low and was enhanced moderately by stimulation with LPS. By contrast, the spontaneous production of NAP-1/IL-8 was 3- to 10-fold higher in PBMC and even much higher in SFMC from RA patients. In all instances, the yield of NAP-1/IL-8 could be enhanced by stimulation in culture. In addition to LPS, rheumatoid factor containing immune complexes, zymosan, and IL-1 were highly effective in inducing NAP-1/IL-8 production, while IL-3, GM-CSF, tumor necrosis factor (TNF), and IL-2 were somewhat less potent. An inhibitory effect was obtained with IFN-gamma, which significantly decreased the spontaneous NAP-1/IL-8 release from SFMC and the IL-1- and LPS-induced NAP-1/IL-8 from RA and control PBMC. Inhibition was also observed with glucocorticoids. The production of NAP-1/IL-8 was markedly reduced by dexamethasone in phagocytosis-stimulated PBMC, and almost totally inhibited in SFMC obtained from joints after intraarticular administration of betamethasone. By contrast, the cyclooxygenase inhibitor, indomethacin, tended to increase the NAP-1/IL-8 yield from PBMC in culture. PMID- 1899428 TI - Multiple defects in muscle glycogen synthase activity contribute to reduced glycogen synthesis in non-insulin dependent diabetes mellitus. AB - To define the mechanisms of impaired muscle glycogen synthase and reduced glycogen formation in non-insulin dependent diabetes mellitus (NIDDM), glycogen synthase activity was kinetically analyzed during the basal state and three glucose clamp studies (insulin approximately equal to 300, 700, and 33,400 pmol/liter) in eight matched nonobese NIDDM and eight control subjects. Muscle glycogen content was measured in the basal state and following clamps at insulin levels of 33,400 pmol/liter. NIDDM subjects had glucose uptake matched to controls in each clamp by raising serum glucose to 15-20 mmol/liter. The insulin concentration required to half-maximally activate glycogen synthase (ED50) was approximately fourfold greater for NIDDM than control subjects (1,004 +/- 264 vs. 257 +/- 110 pmol/liter, P less than 0.02) but the maximal insulin effect was similar. Total glycogen synthase activity was reduced approximately 38% and glycogen content was approximately 30% lower in NIDDM. A positive correlation was present between glycogen content and glycogen synthase activity (r = 0.51, P less than 0.01). In summary, defects in muscle glycogen synthase activity and reduced glycogen content are present in NIDDM. NIDDM subjects also have less total glycogen synthase activity consistent with reduced functional mass of the enzyme. These findings and the correlation between glycogen synthase activity and glycogen content support the theory that multiple defects in glycogen synthase activity combine to cause reduced glycogen formation in NIDDM. PMID- 1899429 TI - Increased apo A-I and apo A-II fractional catabolic rate in patients with low high density lipoprotein-cholesterol levels with or without hypertriglyceridemia. AB - Low HDL-cholesterol (HDL-C) levels may elevate atherosclerosis risk, and often associate with hypertriglyceridemia (HTG); however, the metabolic causes of low HDL-C levels with or without HTG are poorly understood. We studied the turnover of radioiodinated HDL apolipoproteins, apo A-I and apo A-II, in 15 human subjects with low HDL-C, six with normal plasma TG levels (group 1) and nine with high TG (group 2), and compared them to 13 control subjects with normal HDL-C and TG levels (group 3). The fractional catabolic rate (FCR) was equally elevated in groups 1 and 2 vs. group 3 for both apo A-I (0.313 +/- 0.052 and 0.323 +/- 0.063 vs. 0.245 +/- 0.043 pools/d, P = 0.003) and apo A-II (0.213 +/- 0.036 and 0.239 +/- 0.037 vs. 0.185 +/- 0.031 pools/d, P = 0.006). Thus, high FCR characterized low HDL-C regardless of the presence or absence of HTG. In contrast, transport rate (TR) of apo A-I did not differ significantly among the groups and the apo A II TR differed only between groups 2 and 3 (2.15 +/- 0.57, 2.50 +/- 0.39, and 1.83 +/- 0.48 mg/kg per d for groups 1 to 3, respectively, P = 0.016). Several HDL-related factors were similar in groups 1 and 2 but differed in group 3, as with FCR, including the ratio of lipoprotein lipase to hepatic lipase activity (LPL/HL) in post-heparin plasma, the ratio of the HDL-C to apo A-I plus apo A-II levels, and the percent of tracer in the d greater than 1.21 fraction. In linear regression analysis HDL-C levels correlated inversely with the FCR of apo A-I and apo A-II (r = -0.74, P less than 0.0001 for both). Major correlates of FCR were HDL-C/apo A-I + apo A-II, LPL/HL, and plasma TG levels. We hypothesize that lipase activity and plasma TG affect HDL composition which modulates FCR, which in turn regulates HDL-C. Thus, HTG is only one of several factors which may contribute to elevated FCR and low HDL-C. Given the relationship of altered HDL composition with high FCR and low HDL-C levels, factors affecting HDL composition may increase atherosclerosis susceptibility. PMID- 1899430 TI - Selective expansion of human gamma delta T cells by monocytes infected with live Mycobacterium tuberculosis. AB - Gamma delta (gamma delta) T cell receptor (TCR) expressing T cells comprise 3% of human peripheral blood lymphocytes, yet their role in the immune response remains largely unknown. There is evidence both in humans and in animal models that these cells participate in the immune response to mycobacterial antigens. In mice, exposure to mycobacterial antigens leads to the expansion of gamma delta T cells in draining lymph nodes and lungs. In humans, gamma delta T cell lines with reactivity to mycobacterial antigens have been derived from synovial fluid of a rheumatoid arthritis patient, skin lesions of leprosy patients, and peripheral blood of a healthy tuberculin reactor. Very little is known, however, about the factors which induce human gamma delta T cells to expand. In studies comparing the human T cell response to live and heat-killed Mycobacterium tuberculosis (MT), we have found that monocytes infected with live MT are very effective inducers of human gamma delta T cell expansion. After 7 d of exposure to live MT, gamma delta T cells were greatly increased in all healthy tuberculin reactors (PPD+) tested and frequently were the predominant T cell population. In contrast, heat-killed MT or purified protein products of MT induced a CD4+, alpha beta TCR+ T cell response with very little increase in gamma delta T cells. Furthermore, a similar selective induction of gamma delta T cells was observed when monocytes infected with live Salmonella were used to stimulate T cells. Heat-killed Salmonella, like heat-killed MT, induced a predominantly CD4+ alpha beta TCR+ T cell response. These findings suggest that human gamma delta T cells are a major reactive T cell population during the early stages of infection with living intracellular bacteria and are therefore likely to exert an important role in the initial interaction between host and parasite. PMID- 1899431 TI - Essential role for interferon-gamma and interleukin-6 in autoimmune insulin dependent diabetes in NOD/Wehi mice. AB - Experimental studies in vitro suggest that cytokines are important mediators in the pathogenesis of autoimmune insulin-dependent diabetes mellitus (IDDM). However, there is little evidence for the role of cytokines in vivo, either in humans or in the spontaneous animal models of IDDM such as the NOD mouse or BB rat. To address this question, we used the model of cyclophosphamide (CYP) induced autoimmune diabetes in the NOD/Wehi mouse to examine for (a) the production of IFN-gamma and IL-6 from isolated islets, and (b) the effect of anti IFN-gamma or anti IL-6 monoclonal antibodies on the development of diabetes. After cyclophosphamide, the majority of these mice develop of mononuclear cell infiltrate (insulitis) which by 10-14 d is associated with beta cell destruction. IFN-gamma activity at low levels (2.7 +/- 0.3 U/ml) could be detected only in culture supernatants from islets isolated at day 7 post-cyclophosphamide. In contrast, IL-6 activity progressively increased from 457 +/- 44 U/ml at day 0 to 6,020 +/- 777 U/ml at day 10. Culture of islets with anti-CD3 monoclonal antibody resulted in a significant increase in IFN-gamma activity from 41 +/- 7 U/ml at day 0 to 812 +/- 156 U/ml at day 10. Mice given either anti-IFN-gamma or anti-IL 6 antibody had a significantly reduced (P less than 0.001) incidence of diabetes and especially with IFN-gamma, decreased severity of insulitis. We conclude that IFN-gamma and IL-6 have essential roles in the pathogenesis of pancreatic islet beta cell destruction in this model. PMID- 1899432 TI - Flecainide acetate treatment of paroxysmal supraventricular tachycardia and paroxysmal atrial fibrillation: dose-response studies. The Flecainide Supraventricular Tachycardia Study Group. AB - The dose-response relations for efficacy and tolerance of the antiarrhythmic drug flecainide acetate were studied in 28 patients with paroxysmal supraventricular tachycardia (Group 1) and 45 patients with paroxysmal atrial fibrillation or flutter (Group 2). Recurrent symptomatic tachycardia was documented with use of transtelephonic electrocardiographic recording. Patients received flecainide in doses of 25, 50, 100 and 150 mg twice daily and placebo for 1 month treatment periods. Among 14 patients in Group 1 who qualified for efficacy analysis, 4 (29%) had no tachycardia while taking placebo. The number with no tachycardia increased with progressively larger flecainide doses; with the 150 mg twice daily dose, 12 (86%) of 14 patients had no tachycardia (p less than 0.01 for overall differences among all treatments). Among 28 patients in Group 2, 2 (7%) had no tachycardia while taking placebo. The number with no tachycardia also increased with progressively larger flecainide doses; with the 150 mg twice daily dose, 17 (61%) of 28 patients had no tachycardia (p less than 0.01 for overall differences among all treatments). Noncardiac adverse experiences were the leading cause of premature study discontinuation during flecainide treatment periods (five patients in Group 1 and six patients in Group 2). PMID- 1899433 TI - Myocardial infarction with minimal coronary atherosclerosis in the era of thrombolytic reperfusion. The Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) Study Group. AB - The incidence of minimal residual atherosclerotic coronary obstruction after successful intravenous thrombolytic therapy was evaluated in 799 patients with acute myocardial infarction. Minimal residual coronary obstruction (less than or equal to 50%) was observed on selective coronary angiography performed 90 min after initiation of thrombolytic therapy in 43 patients (5.5%). In 42 other patients (5.4%), a greater than 50% but less than 100% residual stenosis noted at 90 min demonstrated further resolution of obstruction to less than 50% at an angiographic follow-up study 7 to 10 days later. Patients with minimal residual coronary obstruction were significantly younger (52 +/- 10.7 versus 56.7 +/- 10 years; p = 0.002) and had less multivessel coronary disease (p less than 0.001), better initial left ventricular ejection fraction (54 +/- 12% versus 50.2 +/- 11.4%; p = 0.006) and a lower in-hospital mortality rate (1% versus 7%; p = 0.04) than did patients who had a significant (greater than 50%) residual coronary obstruction after intravenous thrombolysis. Long-term follow-up study of patients with a minimal coronary lesion (average 1.5 +/- 0.6 years) and those with significant residual stenosis (average 1.6 +/- 0.7 years) demonstrated that the incidence of death (2.4% in patients with minimal stenosis versus 3.5% in those with significant stenosis) and recurrent myocardial infarction (5% each) were similar in both groups. New strategies are needed to prevent coronary rethrombosis in patients with minimal atherosclerosis after thrombolytic therapy for acute myocardial infarction. PMID- 1899434 TI - Late potentials on signal-averaged electrocardiograms and patency of the infarct related artery in survivors of acute myocardial infarction. AB - This study evaluated the relation between patency of the infarct-related artery and the presence of late potentials on the signal-averaged electrocardiogram (ECG) in 124 consecutive patients (98 men, 26 women; mean age 59 years) with acute myocardial infarction receiving thrombolytic therapy, acute percutaneous transluminal coronary angioplasty or standard care. All patients were studied by coronary angiography, measurement of ejection fraction and signal-averaged ECG. The infarct-related artery was closed in 51 patients and open in 73. Among patients with no prior myocardial infarction undergoing early attempted reperfusion therapy, a patent artery was associated with a decreased incidence of late potentials (20% versus 71%; no significant difference in ejection fraction). In the 48 patients receiving thrombolytic agents within 4 h of symptom onset, the incidence of late potentials was 24% and 83% among patients with an open or closed artery, respectively (p less than 0.04). The most powerful predictors of late potentials were the presence of a closed infarct-related artery, followed by prior infarction and patient age. Among patients receiving thrombolytic agents within 4 h of symptom onset, the only variable that was predictive of the presence of late potentials was a closed infarct-related artery. These data imply that reperfusion of an infarct-related artery has a beneficial effect on the electrophysiologic substrate for serious ventricular arrhythmias that is independent of change in left ventricular ejection fraction as an index of infarct size. These findings might explain, in part, the low late mortality rate in survivors of myocardial infarction with documented reperfusion of the infarct related artery. PMID- 1899435 TI - Methionine restores the venodilative response to nitroglycerin after the development of tolerance. AB - Depletion of sulfhydryl groups may contribute to nitroglycerin tolerance after long-term exposure. This study was performed to assess whether methionine, an amino acid capable of augmenting sulfhydryl availability, would restore the venodilative response to sublingual nitroglycerin once tolerance had developed. The venodilative response to organic nitrates was assessed with use of the equilibration technique of forearm plethysmography. Venous volume was measured before and after sublingual administration of 0.4 mg of nitroglycerin at baseline study and after 5 g of intravenous methionine. Retesting was performed 2 h after application of a 10 mg nitroglycerin patch and compared with the response after 74 h of nitroglycerin patch exposure before and after intravenous methionine. Methionine alone had no intrinsic venodilative action. Although the venous volume at rest was unchanged after methionine administration, the response to sublingual nitroglycerin was potentiated compared with baseline values (37 +/- 15% versus 32 +/- 13%, p less than 0.02). During nitroglycerin patch exposure, the response to sublingual nitroglycerin was significantly attenuated at 74 h compared with the response at 2 h of exposure (16 +/- 10% versus 31 +/- 13%, p less than 0.001). The venodilative response to sublingual nitroglycerin was restored at 74 h after methionine administration (35 +/- 14% versus 16 +/- 10%, p less than 0.001). Thus, methionine potentiates the venodilative effect of sublingual nitroglycerin both immediately and in the setting of nitrate tolerance. PMID- 1899436 TI - Actual or ideal body weight: which should be used to predict energy expenditure? AB - Assessing energy expenditure in obese people is problematic. Two questions arise: Can we predict energy expenditure accurately? Does actual or ideal body weight better predict energy expenditure? Two groups of obese subjects--65 hospitalized adults and 65 nonhospitalized adults--were studied. Both groups had actual body weights that were at least 30% above ideal body weights. For both groups, energy expenditure was measured by indirect calorimetry and calculated using the variables sex, actual and ideal body weight, age, and ventilatory status. All but three patients were receiving nutrition support by the enteral route (either orally or by tube) or by the parenteral route (with hypertonic dextrose, amino acid, and fat). The nonhospitalized subjects fasted during measurements of energy expenditure. Regression equations were derived to predict energy expenditure. Actual body weight better predicted energy expenditure than did ideal body weight. We conclude that actual weight should be used to predict energy expenditure in obese individuals. PMID- 1899437 TI - Geropsychiatry in long-term care: a nurse-centered approach. AB - High prevalence rates of psychiatric disorders and disruptive behaviors in nursing home residents create the need for structured programs of psychiatric consultation and teaching in the long-term care setting. Over 40 months, 473 residents were evaluated by a psychiatric consultation-liaison clinical nurse specialist; 100 of these cases were reviewed in detail. Apparent depression was the most common reason for referral, and depressive and adjustment disorders were the most common diagnostic conclusions of the consultation team. Behavioral complications of dementia were also frequently diagnosed. Treatment recommendations usually included the development of a behavioral management plan, but the institution of psychotropic medications, usually antidepressants, was indicated in about one-fifth of the 100 cases. Treatment interventions were effective in the majority of cases. About one-half of the problems prompting referral were within the expertise of the nurse specialist and did not require the direct involvement of the geropsychiatrist. This nurse-centered consultation model proved effective, well accepted, and easy to implement. PMID- 1899438 TI - Assessment and quality control of incontinence care in long-term nursing facilities. AB - A statistical quality-control process was used to assess how well incontinence management procedures were being implemented by indigenous nursing staff in four nursing homes. Eighty-one incontinent patients were treated with the prompted voiding toileting procedure. Thirty-six of these patients proved responsive to the toileting procedures, and nursing home staff was instructed to maintain the toileting program for these responsive patients. The first part of the quality control model involved setting job standards specifying how dry the patients should be if toileted on a 2-hour schedule. Second, a job-monitoring control chart was used to continuously assess how well the job standards were being met. The remaining forty-five patients, who were unresponsive to the toileting protocol, were managed with a 2-hour changing schedule. Job standards specifying how wet (volume) the patient would be if changed on a two-hour basis were set. Control-chart monitoring of these patients urine output assessed how well the changing procedures were being implemented. Incontinence care in nursing homes is difficult to supervise because of problems in measuring how consistently nursing aides change or toilet patients. This paper describes a management system for effective incontinence care. PMID- 1899439 TI - A new paradigm for home care. PMID- 1899441 TI - Resistance in murine schistosomiasis is contingent on activated IL-2 receptor bearing L3T4+ lymphocytes, negatively regulated by Lyt-2+ cells, and uninfluenced by the presence of IL-4. AB - These studies assess the roles of subpopulations of T lymphocytes in inducing and modulating resistance to Schistosoma mansoni. C57BL/6 mice were depleted in vivo of L3T4+, Lyt-1+, Lyt-2+, IL-2R+ cells, or IL-4 by administration of appropriate mAb. Resistance and various correlative parameters of the immune response were studied in normal, depleted, and congenitally athymic mice. Depletion of T lymphocytes by anti-L3T4 or anti-IL-2R mAb reduced the development and expression of resistance, IgG2a and IgE antibody formation, and delayed type hypersensitivity reactivity against schistosome Ag. Depletion with anti-IL-4 antibody led to profound suppression of IgE-eosinophil-mediated antibody dependent cell-mediated cytotoxicity and passive cutaneous anaphylaxis responses against the parasite and no effect on IgG2a antibody, Ag-mediated blast transformation, or resistance. Depletion of Lyt-2+ cells produced augmented development and expression of resistance and an increase in the immunological parameters of anti-schistosome reactivity. These studies suggest that protective immunity to S. mansoni in mice, induced by irradiated cercariae, is dependent on L3T4+, IL-2R+ lymphocytes and negatively regulated by Lyt-2+ cells. IL-4 does not appear to be essential for the development of resistance but is essential for the IgE response to the parasite. PMID- 1899440 TI - Monocyte chemotaxis and activating factor production by keratinocytes in response to IFN-gamma. AB - Monocytes accumulate in the epidermis and along the dermo-epidermal junction in several different inflammatory skin diseases. To determine whether human epidermal keratinocytes elaborate a specific chemotaxin responsible for the accumulation of monocytes at these anatomic sites, monocyte chemotactic activity in conditioned 16-h cultured keratinocyte supernatants were assayed using human peripheral blood monocytes as the target cell. Dilutional analysis revealed directed monocyte migration in IFN-gamma-treated (100 U/ml) keratinocyte supernatants (80% maximal FMLP response) which was 10-fold more than IFN-gamma itself or untreated keratinocyte activity alone. Gel filtration chromatography revealed that this activity eluted just ahead of a 12.5-kDa molecular mass marker. Blocking studies demonstrated that a rabbit polyclonal antibody to monocyte chemotaxis and activating factor (MCAF) inhibited all monocyte chemotaxis by greater than 80%. Keratinocytes were metabolically labeled with 35S cysteine/methionine, and after 16 h incubation the supernatants immunoprecipitated with the same anti-MCAF antibody. MCAF was detected as a protein doublet of 12 and 9 kDa only in IFN-gamma-treated (100 U/ml) keratinocyte supernatants. Incubation with IFN-gamma and TNF-alpha (250 U/ml) in combination resulted in increased production of MCAF protein. By Northern blot analysis, MCAF mRNA was constitutively expressed in keratinocytes and upregulated only in the presence of IFN-gamma. TNF-alpha, IL-1 beta, transforming growth factor-beta and phorbol esters had no positive or negative influence on MCAF mRNA. These studies demonstrate that biologically active MCAF is elaborated by human epidermal keratinocytes upon activation by IFN-gamma, a cytokine also required for the induction of adherence between monocytes and keratinocytes. Keratinocyte-derived MCAF is likely to be important in the regulation of cutaneous monocyte trafficking and may also be responsible for the recruitment of Langerhans cells and dermal dendrocytes, which share many phenotypic features with monocytes/macrophages, to their anatomic locations in skin. PMID- 1899442 TI - High frequency expression of S107 VH genes by peritoneal B cells of B10.H-2aH 4bP/WTS mice. PMID- 1899444 TI - Hydrogen peroxide as a mediator of dopac-induced effects on melanoma cells. AB - Dopac increases tyrosinase activity and exerts cytotoxic effects in cultures of human melanoma cells. The possible role of hydrogen peroxide in these actions was examined. Catalase (100 micrograms/ml) completely reversed the cytotoxic action of 0.3 mM dopac and reduced its tyrosinase-stimulating effect by approximately one half. The results show that extracellular hydrogen peroxide is a mediator of both the tyrosinase-stimulating and cytotoxic actions of dopac. Analysis of the degradation products of melanin from dopac-treated melanoma cells after hydriodic acid (HI) hydrolysis revealed the presence of aminohydroxy-phenylacetic acid (AHPAc). This substance is obtained by HI hydrolysis of melanin formed by oxidation of cysteinyl-dopac. Thus, the presence of AHPAc indicates that dopac is transported into the melanocytes where it serves as a substrate for tyrosinase. PMID- 1899443 TI - Interleukins 1 alpha and 6 and tumor necrosis factor-alpha are paracrine inhibitors of human melanocyte proliferation and melanogenesis. AB - Interleukin (IL)-1 alpha, IL-6, and tumor necrosis factor (TNF)-alpha are epidermal cytokines that produce many similar biologic effects. We have investigated the possibility that these cytokines act as regulators of melanization and proliferation of cultured normal human melanocytes (NHM). All three cytokines elicited a dose-dependent decrease in the activity of the enzyme tyrosinase after 48 h of treatment. IL-1 alpha had the greatest inhibitory effect, resulting in a 22% inhibition of tyrosinase activity at a concentration of 3 x 10(-14) M. An equivalent effect was elicited by 4 x 10(-11) M IL-6 and 10( 11) M TNF-alpha. All three cytokines also inhibited melanocyte proliferation, as measured by a decrease in the rate of 3H-thymidine incorporation and an increase in doubling time. IL-1 alpha at 6 x 10(-14) M, 6 x 10(-13) M, and 3 x 10(-12) M, TNF-alpha at 10(-10) M, 10(-9) M, and 10(-8) M, and IL-6 at 4 x 10(-10) and 1.2 x 10(-9) M produced a dose-dependent inhibition of 3H-thymidine incorporation. The effects of IL-1 alpha, TNF-alpha, and IL-6 were cytostatic, not cytotoxic, because melanocytes remained viable following several treatments with the cytokines. Also, melanocytes treated with IL-1 alpha and TNF-alpha recovered and resumed proliferation after cessation of treatment. These effects of IL-1 alpha, IL-6 and TNF-alpha do not seem to be mediated by stimulation of eicosanoid production, because inhibition of arachidonic acid (AA) metabolism by indomethacin, a cyclooxygenase inhibitor, and nordihydroguaiaretic acid, a lipoxygenase inhibitor, did not reverse the inhibitory effects on either proliferation or tyrosinase activity of NHM. This is the first demonstration that NHM respond to epidermal cytokines, and suggests a role for paracrine and possibly autocrine regulation of melanocytes by immune modulators. PMID- 1899445 TI - Extracellular binding sites of IgA anti-jejunal antibodies on normal small bowel detected by indirect immunoelectronmicroscopy. AB - Patients with dermatitis herpetiformis (DH) have IgA deposition in the papillary dermis and in the lamina propria of the small bowel. In addition, most of DH patients' sera contain IgA class anti-reticulin antibodies, anti-endomysium antibodies (EMA), and anti-jejunal antibodies (JAB) during times of gluten intake. In previous studies, JAB and EMA seemed to be identical and related to the group of anti-reticulin antibodies. In the present study, pre-embedding en bloc immunoelectronmicroscopic methods were applied for analysis of the ultrastructural binding sites of JAB on monkey and rabbit small bowels. These substrates were incubated with sera from DH patients strongly positive for JAB. Simultaneous investigations with the PAP technique and with 5 nm gold-labeled protein A or second antibodies visualized the bound IgA identically: it was associated with collagen fibrils underlying the epithelial and cryptal basement membranes and with collagen fibrils around capillaries. Staining was also detected along the endomysial collagen fibrils of smooth muscle layers, around elastica and smooth muscle cells of blood vessel walls, and along collagen fibrils near smooth muscle cells in the lamina propria. Neither the peroxidase product nor gold deposition was detected directly on the fibers, but was associated with amorphous material surrounding collagen fibers of different diameters. The distribution of JAB-stained structures corresponded to the localization of reticulin network of the small bowel. Our data indicate that JAB recognize an antigen or antigens associated with an amorphous component of the reticulin-collagen structure of jejunum and may have identical binding sites, as anti-reticulin antibodies and EMA. PMID- 1899446 TI - Estrogen-enhanced neurite growth: evidence for a selective induction of Tau and stable microtubules. AB - Estrogen stimulates the neurite outgrowth response of medial basal hypothalamic neurons maintained in culture. We show here that one effect of estrogen is to promote an increase in tau, but not in tubulin, microtubule-associated protein 1a (MAP-1a), or MAP-2 protein levels. This response precedes and accompanies an increase in stable microtubules and in neurite length. Taken collectively, our data suggest that estrogen-enhanced neurite growth is mediated by a selective induction of microtubule-stabilizing factors, namely, the tau proteins. PMID- 1899447 TI - Ribose facilitates thallium-201 redistribution in patients with coronary artery disease. AB - To investigate whether i.v. infusion of ribose, an adenine nucleotide precursor, postischemia facilitates thallium-201 (201Tl) redistribution and improves identification of ischemic myocardium in patients with coronary artery disease (CAD), 17 patients underwent two exercise 201Tl stress tests, performed 1-2 wk apart. After immediate postexercise planar imaging, patients received either i.v. ribose (3.3 mg/kg/min x 30 min) or saline as a control. Additional imaging was performed 1 and 4 hr postexercise. Reversible defects were identified by count profile analysis. Significantly more (nearly twice as many) reversible 201Tl defects were identified on the post-ribose images compared to the post-saline (control) images at both 1 and 4 hr postexercise (p less than 0.001). Quantitative analyses of the coronary arteriogram was available in 13 patients and confirmed that the additional reversible defects were in myocardial regions supplied by stenosed arteries. We conclude that ribose appears to facilitate 201Tl redistribution in patients with CAD and enhances identification of ischemic myocardium. PMID- 1899448 TI - Enzyme activities associated with carcinogen metabolism in liver and nonhepatic tissues of rats maintained on high fat and food-restricted diets. AB - The influence of high fat or food-restricted diets on key enzymes associated with polycyclic aromatic hydrocarbon metabolism was assessed in liver, lung, kidney and stomach of rats. Animals had access ad libitum to the AIN-76A purified diet (control) or were given 65% of the intake of controls for 3 wk. The high fat diet was isoenergetic to the control diet by substituting corn oil for equal energy from carbohydrate and addition of cellulose to obtain equal energy density. Activities of arylhydrocarbon hydroxylase and 7-ethoxycoumarin O-deethylase were significantly increased in lungs of food-restricted rats and decreased by the high fat diet but were not altered in liver. Both diets increased arylhydrocarbon hydroxylase approximately twofold in kidney. Glucose 6-phosphate and 6 phosphogluconate dehydrogenase were lowered in lung, kidney and liver by the high fat diet. Hepatic glutathione S-transferase was increased by high fat feeding. Food restriction decreased activities of arylsulfatase and beta-glucuronidase about 40% in lung. Hepatic arylsulfatase was also decreased about 40% by this treatment. Changes in hydrolase activities in livers and lungs of animals maintained on restricted diets raises in the interesting possibility that net production of glucuronide and sulfate conjugates of carcinogens by the liver and their hydrolysis in lung is altered by food restriction. PMID- 1899449 TI - Effect of Staphylococcus epidermidis on adherence of Pseudomonas aeruginosa and Proteus mirabilis to polymethyl methacrylate (PMMA) and gentamicin-containing PMMA. AB - The goals of this study were to determine 1) effect of Staphylococcus epidermidis adherence and biofilm production on adherence of the opportunistic pathogens Proteus mirabilis and Pseudomonas aeruginosa to polymethyl methacrylate (PMMA); 2) if the biofilm killed by autoclaving altered adherence of other organisms; 3) if adherence of S. epidermidis to gentamicin-containing PMMA altered adherence of the opportunistic pathogens P. mirabilis and P. aeruginosa to gentamicin containing PMMA. Results show that biofilms formed by S. epidermidis, whether alive or dead, significantly increased adherence of Pseudomonas. Adherence of Proteus was significantly increased on dead biofilms and increased, but not significantly (p = less than 0.1), on live ones. Greatest adherence seen in the study was to autoclaved biofilms. Significant adherence of Proteus and Pseudomonas was found on gentamicin-containing PMMA specimens, which were preincubated with S. epidermidis for formation on the biofilm. These results indicate that a biofilm is formed on PMMA-gentamicin specimens and this may impair the ability of gentamicin to kill other organisms. PMID- 1899450 TI - Schistosoma mansoni-New Zealand rabbit model: resistance induced by infection followed by active immunization with protective antigens. AB - In previous studies, rabbits immunized with adult worm antigens released from fresh adult schistosomes incubated in saline media showed a significant level of protection against challenge parasites. Focusing on the rabbit-Schistosoma mansoni model, concomitant immunity was investigated. A peculiar form of response to cercarial infection was observed: rabbits subjected to percutaneous infection and similar reinfections at different times after primary infection killed schistosomula from the challenge infection as well as established parasites from the primary infection. In this study the challenge infection stimulus was replaced by active immunization with an adult worm-derived protective antigenic mixture. The results show that immunization of New Zealand rabbits with an adult worm antigenic extract is capable of inducing a response that results in a significant reduction of the mean worm burden of the primary infection earlier than did homologous infection, as compared to worm reduction due to a second infection. PMID- 1899451 TI - Fixing coccidian oocysts is not an adequate solution to the problem of preserving protozoan type material. AB - Fresh (36 days old) sporulated oocysts of Eimeria nieschulzi were divided into 7 groups. Control oocysts were maintained at 23 C in 2% aqueous (w/v) K2Cr2O7. The 6 experimental groups were mixed with either Bouin's solution, 10% aqueous (v/v) buffered formalin, Karnovsky's solution, glutaraldehyde, paraformaldehyde, or 70% aqueous (v/v) ethanol (EtOH). After 115 days, oocysts from all 7 groups were examined under oil immersion to determine the effect of fixation on their structural integrity. The parameters examined were lengths and widths of oocysts and sporocysts, percent sporulation (%S), and percent crenation (%C) of oocysts and sporocysts. The highest destruction (%S and %C) occurred in oocysts exposed to glutaraldehyde and Karnovsky's fixatives where 100% of both oocysts and sporocysts crenated and only 8% and 48%, respectively, remained sporulated. Of the oocysts in paraformaldehyde, 93% remained sporulated, but 95%of these oocysts and 100% of the sporocyst crenated. In Bouin's solution, 75% of the oocysts were intact structurally, but of these, only 60% were still sporulated with 70% of their sporocysts crenated. Oocysts preserved in 70% EtOH were 80% intact and 70% remained sporulated, but nearly 60% of their sporocysts collapsed even though the oocyst walls were intact. Oocysts preserved in 10% buffered formalin maintained structural integrity but had lower numbers of sporulated oocysts (84%) and greater numbers of crenated oocysts (18%) than control oocysts maintained in the dichromate solution (95% and 0%, respectively). PMID- 1899452 TI - Novel, potent aldose reductase inhibitors: 3,4-dihydro-4-oxo-3-[[5 (trifluoromethyl)-2-benzothiazolyl] methyl]-1-phthalazineacetic acid (zopolrestat) and congeners. AB - A new working hypothesis that there is a hitherto unrecognized binding site on the aldose reductase (AR) enzyme with strong affinity for benzothiazoles was pursued for the design of novel, potent aldose reductase inhibitors (ARIs). The first application of this hypothesis led to a novel series of 3,4-dihydro-4-oxo-3 (benzothiazolylmethyl)-1-phthalazineacetic+ + + acids. The parent of this series (207) was a potent inhibitor of AR from human placenta (IC50 = 1.9 x 10(-8) M) and was orally active in preventing sorbitol accumulation in rat sciatic nerve, in an acute test of diabetic complications (ED50 = 18.5 mg/kg). Optimization of this lead through medicinal chemical rationale, including analogy from other drug series, led to more potent congeners of 207 and culminated in the design of 3,4 dihydro-4-oxo-3-[[5-(trifluoromethyl)-2-benzothiazolyl] methyl]-1 phthalazineacetic acid (216, CP-73,850, zopolrestat). Zopolrestat was found to be more potent than 207, both in vitro and in vivo. Its IC50 against AR and ED50 in the acute test were 3.1 x 10(-9)M and 3.6 mg/kg, respectively. Its ED50s in reversing already elevated sorbitol accumulation in rat sciatic nerve, retina, and lens in a chronic test were 1.9, 17.6, and 18.4 mg/kg, respectively. It was well absorbed in diabetic patients, resulting in high blood level, showed a highly favorable plasma half-life (27.5 h), and is undergoing further clinical evaluation. An assortment of synthetic methods used for the construction of benzothiazoles, including an efficient synthesis of zopolrestat, is described. Structure-activity relationships in the new series are discussed. PMID- 1899453 TI - On the optimization of hydrophobic and hydrophilic substituent interactions of 2,4-diamino-5-(substituted-benzyl)pyrimidines with dihydrofolate reductase. AB - The inhibition constants (Kiapp) were obtained from the action of 68 2,4-diamino 5-(substituted-benzyl)pyrimidines on dihydrofolate reductase from an Escherichia coli strain MB 1428. Subsequently, these results were used to formulate appropriate quantitative structure-activity relationships (QSAR). Once again these equations emphasize the paramount importance of steric/dispersion factors in enhancing antibacterial potency. Hydrophobicity also plays a role, albeit a minor one. Comparisons with the QSAR obtained versus prokaryotic dihydrofolate reductase (DHFR) demonstrate subtle differences in binding behavior between meta and para substituents which may be effectively maximized in the design of more efficacious and selective antibacterial agents. The bacterial and avian QSAR equations can be used to calculate selectivity indices for trimethoprim, tetroxoprim, and two other specially designed 2,4-diamino-5-(substituted benzyl)pyrimidines. PMID- 1899454 TI - From the Food and Drug Administration. PMID- 1899455 TI - Mortality and duration of hemodialysis treatment. AB - Decrease in the average duration of hemodialysis treatment time is a continuing phenomenon. We investigated the relationship of 3-year mortality to duration of dialysis in a 1984-1985 national random sample of 600 hemodialysis patients from 36 dialysis units. Mortality was negatively associated with duration of dialysis treatments, as shown by the Cox model, adjusted for other patient and dialysis unit covariates. With adjustment for other covariates, patients receiving an average dialysis treatment duration of less than 3.5 hours had relative mortality risks of 1.17 to 2.18 compared with those with treatments longer than 3.5 hours (mortality risk of 1.0). Reverse causation (the possibility that more seriously ill patients received dialysis for a shorter time) appears unlikely. We conclude that duration of the dialysis procedure is an important element in determining patient mortality as one of the factors determining the adequacy of dialysis. PMID- 1899456 TI - Mortality and the length of dialysis. PMID- 1899457 TI - Example of prepublication data release: immunoglobulin for concomitant infections. PMID- 1899458 TI - Nasogastric tubes. PMID- 1899459 TI - Intracellular pH in individual pituitary cells: measurement with a dual emission pH indicator. AB - Intracellular pH (pHi) can now be measured at the single cell level using dual emission wavelength microspectrofluorimetry with the fluorescent pH indicator SNARF 1 and its membrane permeant acetoxymethyl ester (SNARF 1/AM). We measured pHi of individual pituitary cells under both basal and stimulated conditions. The emitted fluorescence of SNARF 1 probe was calibrated following experimental manipulations of pHi in two types of rat pituitary cells. The calibration curves obtained in the two cell types were identical. We observed a Gaussian distribution of individual pHi with a wide dispersion (6.95 to 8) in the two cell populations. TRH (10(-7) M) and ionomycin (5 microM) induced a transient acidification followed by a sustained alkalinization, whereas K+ (50 mM) depolarization only exerted a transient acidification. These results show that the dual emission pH indicator SNARF 1 can be used to reliably investigate changes in pHi in individual endocrine cells. PMID- 1899461 TI - Subcellular mechanism of desensitization of the ATP-induced Ca2+ mobilization in human umbilical vein endothelial cells: role of intracellular Ca2+ stores. AB - Confluent monolayers of human umbilical vein endothelial cells subcultured on glass coverslips were loaded with the fluorescent Ca2+ indicator, fura-2. Changes in fura-2 fluorescence were detected by means of a fluorescence spectrophotometer. Both ATP and ADP (0.3-100 microM) caused a concentration dependent transient peak response of the intracellular free calcium concentration ([Ca2+]i), followed by a lower sustained response. AMP and adenosine did not induce detectable changes in [Ca2+]i. The sustained response to ATP was abolished by superfusion with the Ca2(+)-free solution (with 1 mM EGTA), while the transient peak response was uninfluenced. The transient peak response to ATP (30 microM) was inhibited by pre-exposure to ATP in a graded manner depending on the concentration of ATP. The response to ATP recovered after washout for 20 min with the solution containing Ca2+, but not with the Ca2(+)-free solution. The transient peak response to ATP was markedly reduced by preceding exposure to histamine, while the response to histamine was not influenced by pre-exposure to ATP. These findings indicate that depletion and refilling of the ATP-sensitive intracellular Ca2+ store may be responsible for the desensitization and recovery of the ATP-induced [Ca2+]i response. The pharmacological characteristics of the ATP-sensitive intracellular Ca2+ store seem different from those of the histamine sensitive store. PMID- 1899460 TI - (-) deprenyl induces activities of both superoxide dismutase and catalase but not of glutathione peroxidase in the striatum of young male rats. AB - Daily s.c. injection of (-)deprenyl (2.0 mg/kg/day) for three weeks in young male rats caused a threefold increase in superoxide dismutase (SOD) activity in the striatum of the brain compared with the value in saline-injected control rats. Furthermore, the activity of catalase (but not of glutathione peroxidase) was also increased significantly by deprenyl treatment. The results confirmed the previous findings of Knoll on SOD activity and furthermore provided evidence that the activity of catalase is also significantly induced by the drug, which was not found in the previous study. PMID- 1899462 TI - Mosquito-transmitted malaria--California and Florida, 1990. AB - In 1990, two persons--one each in California and Florida--were diagnosed with malaria classified as cryptic; their infections may have been acquired in the United States through bites of mosquitoes that became infected after biting parasitemic migrant workers. PMID- 1899463 TI - Cholera--Peru, 1991. PMID- 1899464 TI - Increase in rubella and congenital rubella syndrome--United States, 1988-1990. AB - In 1988, health departments in the United States reported an all-time low of 225 cases of rubella. However, in 1989, the number of reported cases increased nearly twofold, and in 1990, an additional threefold. As of January 4, 1991, a provisional total of 1093 cases (0.4 cases per 100,000 population) had been reported to the National Notifiable Disease Surveillance System (NNDSS) for 1990- the highest total since 1982 (Figure 1). This report summarizes the increase in rubella and congenital rubella syndrome (CRS) since 1988. PMID- 1899465 TI - Birth defects among low birth weight infants--metropolitan Atlanta, 1978-1988. AB - Approximately 3%-4% of newborn infants have a major birth defect diagnosed during their first year of life. Because many infants with birth defects are born prematurely and/or have intrauterine growth retardation, the rate of birth defects is expected to vary by birth weight. This report summarizes a population based study of the relation between birth defect rates and the birth weight of infants born in metropolitan Atlanta from 1978 through 1988. PMID- 1899466 TI - Effectiveness of a health education curriculum for secondary school students- United States, 1986-1989. AB - The issue of MMWR introduces a new series, "Effectiveness in Disease and Injury Prevention." Future reports in this section will 1) highlight preventive measures that have proven effective and economical in public health and clinical practice and 2) describe how those measures can be integrated more effectively and economically within public health and clinical practice. In addition, reports will address needs, opportunities, and methods for assessing preventive measures. The following report summarizes the evaluation of a school health education curriculum developed to reduce selected health-risk behaviors among young persons. PMID- 1899467 TI - Campylobacter enteritis--New Zealand, 1990. AB - In August-September 1990, an outbreak of Campylobacter enteritis occurred at a camp near Christchurch, New Zealand. This report provides a preliminary summary of the investigation of this outbreak by the New Zealand Communicable Disease Centre and the Canterbury Area Health Board. PMID- 1899468 TI - Update: graphic method for presentation of notifiable disease data--United States, 1990. AB - Since April 1990, data from the National Notifiable Diseases Surveillance System for 14 diseases have been published in a graphic format in the MMWR (Figure I, page 118) (1). The bar graph compares provisional reports for a 4-week period with the mean of 15 4-week totals (from the previous, comparable, and subsequent 4-week periods for the last 5 years) (2). Ratios that exceed national historical limits (calculated based on two standard deviations of the historical baseline) are indicated by striping in the bars. This report summarizes an evaluation of this new method. PMID- 1899469 TI - Maturation of the secretion of thyroid hormone and thyroid-stimulating hormone in the fetus. AB - BACKGROUND: Data on human fetal thyroid function have largely been derived from histologic studies or studies of cord-blood samples obtained at hysterotomy or delivery. These data may not represent true normal values. Cordocentesis (ultrasound-guided blood sampling from the umbilical cord) is a technique that allows investigation of physiologic processes in fetuses not under stress. METHODS: We measured serum thyroid-stimulating hormone, total and free thyroxine (T4), total and free triiodothyronine (T3), and thyroxine-binding globulin in blood samples from 62 fetuses. The samples were obtained by cordocentesis (n = 58) or cardiocentesis (n = 4) at 12 to 37 weeks of gestation. Maternal serum samples were obtained immediately before fetal blood sampling. RESULTS: Fetal serum thyroid-stimulating hormone, thyroxine-binding globulin, and total and free T4 and T3 concentrations increased significantly with the length of gestation (P less than 0.001). The only significant association among these variables, independent of the length of gestation, was between thyroid-stimulating hormone and free T4 (P less than 0.0001). Maternal serum concentrations of these variables did not change during gestation, and there was no significant relation between fetal and maternal values. Most fetal serum concentrations of thyroid stimulating hormone were higher, whereas most serum total and free T3 concentrations were lower than the respective values for normal adults. The fetal serum total T4, free T4, and thyroxine-binding globulin values reached the level of the mean adult values at approximately 36 weeks of gestation. CONCLUSIONS: The increases in fetal serum concentrations of thyroid-stimulating hormone, thyroxine binding globulin, and total and free T4 and T3 during gestation reflect increasing maturation of the pituitary, thyroid, and liver. The finding of increasing fetal serum concentrations of thyroid-stimulating hormone in the presence of increasing thyroid hormone concentrations suggests that the sensitivity of the fetal pituitary gland to negative feedback is limited or is counterbalanced by increasing stimulation by thyrotropin-releasing hormone from the hypothalamus. PMID- 1899470 TI - Recognition of gonadotroph adenomas in women. AB - BACKGROUND: Pituitary adenomas that arise from the gonadotroph cells are being recognized with increasing frequency in men, but they are still rarely recognized in women. This rarity could be the result of an actual difference in occurrence or of greater difficulty in recognition. The tumors are usually recognized in men more than 50 years old, but elevated serum gonadotropin levels in women of that age could be produced by normal gonadotroph cells. METHODS: Because the stimulation of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and the beta subunit of LH (LH beta) by thyrotropin-releasing hormone (TRH) is a characteristic of gonadotroph adenomas in men, we administered TRH to 16 women with apparently nonsecreting pituitary macroadenomas and measured serum FSH, LH, LH beta, and the glycoprotein hormone alpha subunit every 15 minutes for 90 minutes before and 90 minutes after. The results were compared with the responses in 16 healthy women matched for age and in 10 women with macroadenomas secreting prolactin, growth hormone, or corticotropin. The tumors from 12 of the women with nonsecreting adenomas were cultured, and the secretion of FSH, LH, and LH beta in culture was determined. RESULTS: Eleven of the 16 women with apparently nonsecreting adenomas had significant increases in serum LH beta in response to TRH, 3 had FSH responses, and 4 had LH responses. None of the 16 healthy women and none of the 10 women with secreting macroadenomas had LH beta, FSH, or LH responses to TRH. Ten of the 12 adenomas that were cultured secreted readily detectable amounts of FSH, LH, and LH beta, and their secretion in vitro correlated with the patients' responses to TRH in vivo. CONCLUSIONS: Most apparently nonsecreting pituitary macroadenomas in women arise from gonadotroph cells. The majority of these can be recognized, even in postmenopausal women, by the serum LH beta responses to TRH, and some can be recognized by the responses of serum FSH and LH. PMID- 1899471 TI - Gonadotroph-cell pituitary adenomas. PMID- 1899472 TI - A nursing home in your future? PMID- 1899473 TI - Immune recognition. Mls: makes a little sense. PMID- 1899474 TI - Dopa-responsive dystonia: long-term treatment response and prognosis. AB - We report observations on the treatment of 66 patients with presumed dopa responsive dystonia (DRD). Forty-seven of these patients had hereditary disease; 19 had disease of sporadic occurrence. Initial diagnostic confusion with "cerebral palsy" or "spastic diplegia" existed in 16 patients. Several patients benefited from anticholinergic medications and a few from carbamazepine. Levodopa was the most effective treatment in all cases. In the majority, there was an excellent response, with continued long-term clinical stability on levodopa therapy for as long as 10 to 22 years. Four men with sporadic disease and 1 woman with a sister affected with adolescent-onset parkinsonism had similar initial treatment response, but developed "wearing-off" and a less satisfactory response to levodopa within the first few years of treatment. This indicates that some patients with clinical syndromes suggestive of DRD may not have an excellent prognosis on long-term levodopa treatment and may represent misclassified cases of childhood-onset parkinsonism. PMID- 1899475 TI - Aseptic meningitis following cardiac transplantation: clinical characteristics and relationship to immunosuppressive regimen. AB - Neurologic disorders are uncommon but alarming complications of cardiac transplantation. Of 29 patients from the Utah Cardiac Transplant Program (UCTP) who had lumbar puncture because of change in neurologic function, or to assess fever of uncertain etiology, CSF pleocytosis was present in 14 patients, 4 of whom had an active infectious process involving the nervous system. In 10 other patients, CSF pleocytosis with negative cultures appeared following treatment with OKT3 monoclonal antibody. The most prominent clinical signs of this aseptic meningitis syndrome are fever and transient cognitive dysfunction. PMID- 1899476 TI - Regulation of binding of rhoB p20 to membranes by its specific regulatory protein, GDP dissociation inhibitor. AB - We have previously purified from bovine brain cytosol a novel regulatory protein for the GTP-binding proteins of the rho gene family. This regulatory protein, designated as rho GDP dissociation inhibitor (GDI), makes a complex stoichiometrically with the GDP-bound form of the rho gene products and thereby regulates the GDP/GTP exchange reaction by inhibiting the dissociation of GDP from and the subsequent binding of GTP to them. We show here that rho GDI also regulates the binding of rhoB p20, a member of the rho gene products, to various membranes including rat brain synaptic plasma membranes and human erythrocyte ghosts. Both the GDP- and GTP-bound forms of rhoB p20 bound to the membranes. This binding was not inhibited by prior treatment of the membranes with boiling or tryptic digestion, suggesting that a protein molecule of the membranes is not essential for the binding of rhoB p20 to the membranes. rho GDI inhibited the binding of the GDP-bound form of rhoB p20, but not that of the GTP-bound form, to the membranes. Moreover, rho GDI induced the dissociation of the GDP-bound form, but not that of the GTP-bound form, of rhoB p20 exogenously bound to the membranes from them. These results suggest that the rho gene products bind to the membranes, presumably in a reversible manner and that this binding is regulated by their specific GDI. PMID- 1899478 TI - A variant translocation t(2;18) in follicular lymphoma involves the 5' end of bcl 2 and Ig kappa light chain gene. AB - We have examined three cases of human lymphoma bearing a t(2;18)(p11;q21) chromosome translocation. The bcl-2 gene appeared to be rearranged in all three cases and breakpoints were clustered in the 5' flanking region of the gene. In all three cases, bcl-2 was juxtaposed to J segments of the Ig kappa gene. This juxtaposition of the bcl-2 and Ig kappa genes is very similar to the variant chromosome translocations of Burkitt lymphoma that juxtapose the c-myc locus to IgL genes. PMID- 1899477 TI - Sequence and expression of a cDNA encoding MyD118: a novel myeloid differentiation primary response gene induced by multiple cytokines. AB - We report here the full length cDNA sequence and the deduced amino acid sequence of MyD118, a novel myeloid differentiation primary response gene transiently expressed in M1D+ myeloid precursors following induction of terminal differentiation and growth arrest by IL6. MyD118 expression was observed to be induced also in the absence of protein synthesis, following stimulation of M1D+ cells by IL1, LPS and Leukemia Inhibitory Factor (LIF). Detectable levels of MyD118 RNA were observed in myeloid precursor enriched murine bone marrow, but not in several other nonmyeloid murine tissues. PMID- 1899479 TI - A single site mutation in a truncated Fos protein allows it to interact with the TRE in vitro. AB - The Fos and Jun proteins, which are components of the transcription factor AP1, associate through the interaction of their so-called leucine zipper domains and bind strongly and specifically to DNA at phorbol ester-responsive elements. Jun also homodimerizes and binds the same element whereas Fos seems to have no specific affinity for DNA. We show that a single amino-acid change in the leucine zipper of Fos is sufficient to allow a truncated Fos protein to homodimerize and thus form a complex with DNA, even in the absence of Jun. This Fos-derived homodimer recognizes the consensus phorbol-ester responsive element specifically, in vitro. We conclude that the structural requirements for specific DNA binding are present in the Fos protein itself, with the exception of its lack of self affinity. PMID- 1899480 TI - Insect immune response to bacterial infection is mediated by eicosanoids. AB - Inhibition of eicosanoid formation in larvae of the tobacco hornworm Manduca sexta, using specific inhibitors of phospholipase A2, cyclooxygenase, and lipoxygenase, severely weakened the ability of larvae to clear the bacterium Serratia marscescens from their hemolymph. The reduced capability to remove bacteria is associated with increased mortality due to these bacteria. There is a dose-dependent relationship between the phospholipase A2 inhibitor dexamethasone and both the reduced bacterial clearance and increased larval mortality. The dexamethasone effects on larval survival were reversed by treatment with arachidonic acid. Maleic acid, a nonspecific antioxidant, did not interfere with the insects' ability to remove bacterial cells from hemolymph. The larvae were shown to contain all of the C20 polyunsaturated fatty acids necessary for eicosanoid biosynthesis and to be capable of converting radioactive arachidonic acid into several primary prostaglandins. These results strongly suggest that eicosanoids mediate transduction of bacterial infection signals into the complex of cellular and humoral responses that comprise invertebrate immunity. PMID- 1899481 TI - In vivo T-cell activation by staphylococcal enterotoxin B prevents outgrowth of a malignant tumor. AB - Treatment of T cells with staphylococcal enterotoxins in vitro is known to activate T cells in a subset restricted manner based on beta-chain variable region (V beta) gene expression. In particular, staphylococcal enterotoxin B (SEB) activates T cells bearing V beta 7 or V beta 8. We examined the ability of SEB to activate T cells in vivo. Treatment of C3H mice with doses of SEB ranging from 5 to 250 micrograms resulted in a dose-dependent activation of V beta 8+ T cells as reflected by increased interleukin 2 receptor (IL-2R) expression, proliferation to exogenous IL-2 and allogeneic cells, and production of gamma interferon. SEB also caused proliferation of the CD8+ subset of V beta 8+ cells in vivo. Thus, T-cell activation by SEB in vivo appears to be specific since V beta 2+ cells (non-SEB reactive) did not show increases in IL-2R expression similar to those seen with V beta 8+ cells nor did they proliferate. We then studied the ability of these activated cells to potentiate the immune response to a malignant progressor tumor. Treatment of C3H mice with 50 micrograms of SEB at the time of inoculation with tumor fragments resulted in a statistically significant decrease in the frequency of tumor outgrowth. These data demonstrate that treatment of C3H mice with SEB results in specific activation of V beta 8+ cells in vivo and that these activated cells are capable of preventing the outgrowth of a malignant tumor. PMID- 1899482 TI - Depletion of extrinsic pathway inhibitor (EPI) sensitizes rabbits to disseminated intravascular coagulation induced with tissue factor: evidence supporting a physiologic role for EPI as a natural anticoagulant. AB - Although in vitro experiments have established that extrinsic pathway inhibitor (EPI) is the only known plasma inhibitor of factor VIIa-tissue factor (TF) catalytic activity of potential physiologic significance, evidence of its function in vivo has been lacking. TF-induced intravascular coagulation may occur in patients despite normal plasma levels of EPI and, in our earlier studies, normal plasma EPI levels did not protect rabbits from intravascular coagulation induced by an infusion of purified TF (1 microgram/kg). Studies have now been carried out in which plasma EPI levels were reduced in rabbits to below 20% of the initial level by injection of anti-rabbit EPI IgG. Infusion into such animals of purified rabbit TF apoprotein (0.25 microgram/kg) reconstituted into phospholipid vesicles induced substantial disseminated intravascular coagulation. Infusion of control saline or phospholipid vesicles not containing TF was without significant effect as was infusion of TF (0.25 microgram/kg) into animals injected with nonimmune goat IgG. These data establish that EPI can dampen TF induced intravascular coagulation in rabbits. They support the hypothesis that EPI plays a significant role in regulating coagulation resulting from the exposure of blood to trace concentrations of TF during the illnesses and minor injuries of normal existence. PMID- 1899483 TI - Conversion of human choriogonadotropin into a follitropin by protein engineering. AB - Human reproduction is dependent upon the actions of follicle-stimulating hormone (hFSH), luteinizing hormone (hLH), and chorionic gonadotropin (hCG). While the alpha subunits of these heterodimeric proteins can be interchanged without effect on receptor-binding specificity, their beta subunits differ and direct hormone binding to either LH/CG or FSH receptors. Previous studies employing chemical modifications of the hormones, monoclonal antibodies, or synthetic peptides have implicated hCG beta-subunit residues between Cys-38 and Cys-57 and corresponding regions of hLH beta and hFSH beta in receptor recognition and activation. Since the beta subunits of hCG or hLH and hFSH exhibit very little sequence similarity in this region, we postulated that these residues might contribute to hormone specificity. To test this hypothesis we constructed chimeric hCG/hFSH beta subunits, coexpressed them with the human alpha subunit, and examined their ability to interact with LH and FSH receptors and hormone-specific monoclonal antibodies. Surprisingly, substitution of hFSH beta residues 33-52 for hCG beta residues 39-58 had no effect on receptor binding or stimulation. However, substitution of hFSH beta residues 88-108 in place of the carboxyl terminus of hCG beta (residues 94-145) resulted in a hormone analog identical to hFSH in its ability to bind and stimulate FSH receptors. The altered binding specificity displayed by this analog is not attributable solely to the replacement of hCG beta residues 108-145 or substitution of residues in the "determinant loop" located between hCG beta residues 93 and 100. PMID- 1899484 TI - Genetic and molecular characterization of tube, a Drosophila gene maternally required for embryonic dorsoventral polarity. AB - Loss of maternal function of the tube gene disrupts a signaling pathway required for pattern formation in Drosophila, causing cells throughout the embryo to adopt the fate normally reserved for those at the dorsal surface. Here we demonstrate that tube mutations also have a zygotic effect on pupal morphology and that this phenotype is shared by mutations in Toll and pelle, two genes with apparent intracellular roles in determining dorsoventral polarity. We then describe the isolation of a functionally full-length tube cDNA identified in a phenotypic rescue assay. The tube mRNA is expressed maximally early in embryogenesis and again late in larval development, corresponding to required periods of tube activity as defined by distinct maternal and zygotic loss-of-function phenotypes in tube mutants. Sequence analysis of the cDNA indicates that the tube protein contains five copies of an eight-residue motif and shares no significant sequence similarity with known proteins. These results suggest that tube represents a class of protein active in signal transduction at two stages of development. PMID- 1899485 TI - Purification of the active C5a receptor from human polymorphonuclear leukocytes as a receptor-Gi complex. AB - We have isolated, in an active state, the C5a receptor from human polymorphonuclear leukocytes. The purification was achieved in a single step using a C5a affinity column in which the C5a molecule was coupled to the resin through its N terminus. The purified receptor, like the crude solubilized molecule, exhibited a single class of high-affinity binding sites with a Kd of 30 pM. Further, the binding of C5a retained its sensitivity to guanine nucleotides, implying that the purified receptor contained a guanine nucleotide-binding protein (G protein). SDS/PAGE revealed the presence of three polypeptides with molecular masses of 42, 40, and 36 kDa, which were determined to be the C5a binding subunit and the alpha and beta subunits of Gi, respectively. The 36- and 40-kDa polypeptides were identified by immunoblotting and by the ability of pertussis toxin to ADP-ribosylate the 40-kDa molecule. These results confirm our earlier hypothesis that the receptor exists as a complex with a G protein in the presence or absence of C5a. The tight coupling between the receptor and G protein should make possible the identification of the G protein(s) involved in the transduction pathways used by C5a to produce its many biological effects. PMID- 1899486 TI - Aspirin. PMID- 1899487 TI - Sequence-specific antirepression of histone H1-mediated inhibition of basal RNA polymerase II transcription. AB - To understand the principles of control and selectivity in gene expression, the biochemical mechanisms by which promoter- and enhancer-binding factors regulate transcription by RNA polymerase II were analyzed. A general observed repressor of transcription was purified and identified as histone H1. Since many aspects of H1 binding to naked DNA resemble its interaction with chromatin, purified H1 bound to naked DNA was used as a model for the repressed state of the DNA template. Three sequence-specific transcription factors, Sp1, GAL4-VP16, and GAGA factor, were shown to counteract H1-mediated repression (antirepression). In addition, Sp1 and GAL4-VP16, but not the GAGA factor, activated transcription in the absence of H1. Therefore, true activation and antirepression appear to be distinct activities of sequence-specific factors. Furthermore, transcription antirepression by GAL4-VP16 was sustained for several rounds of transcription. These findings, together with previous studies on H1, suggest that H1 participates in repression of the genome in the ground state and that sequence specific transcription factors induce selected genes by a combination of true activation and release of basal repression that is mediated at least in part by H1. PMID- 1899488 TI - A68: a major subunit of paired helical filaments and derivatized forms of normal Tau. AB - Putative Alzheimer disease (AD)-specific proteins (A68) were purified to homogeneity and shown to be major subunits of one form of paired helical filaments (PHFs). The amino acid sequence and immunological data indicate that the backbone of A68 is indistinguishable from that of the protein tau (tau), but A68 could be distinguished from normal human tau by the degree to which A68 was phosphorylated and by the specific residues in A68 that served as phosphate acceptors. The larger apparent relative molecular mass (Mr) of A68, compared to normal human tau, was attributed to abnormal phosphorylation of A68 because enzymatic dephosphorylation of A68 reduced its Mr to close to that of normal tau. Moreover, the LysSerProVal motif in normal human tau appeared to be an abnormal phosphorylation site in A68 because the Ser in this motif was a phosphate acceptor site in A68, but not in normal human tau. Thus, the major subunits of a class of PHFs are A68 proteins and the excessive or inappropriate phosphorylation of normal tau may change its apparent Mr, thus transforming tau into A68. PMID- 1899489 TI - Chemoprotectants for cancer chemotherapy. AB - Maximal dosing of cytotoxic chemotherapy drugs is often limited by the development of severe nonmyelosuppressive toxicities. Numerous studies have demonstrated that sulfur-containing nucleophiles can antagonize the dose-limiting effects of alkylating agents on the genitourinary tract. Examples include the use of sodium thiosulfate to prevent cisplatin-induced renal tubular necrosis and the use of sulfhydryl-containing compounds like N-acetylcysteine and 2 mercaptoethanesulfonate (mesna) to block oxazophosphorine-induced bladder toxicity. Mesna does not block the antitumor action of oxazophosphorines due to its rapid formation of the inactive dimer dimesna in the bloodstream. The active monomer is selectively reduced from dimesna in renal tubule cells, thereby limiting the inactivation of toxins like acrolein to the genitourinary tract. Recent clinical trials suggest that oral mesna has adequate bioavailability (roughly 50% by urinary thiol measurements) to prevent urotoxicity in high-dose ifosfamide regimens. In addition, mesna is stable in aqueous oral formulations. This may facilitate more convenient oral mesna dosing in protocols using high dose cyclophosphamide or ifosfamide. Whereas agents like mesna and sodium thiosulfate complex directly with activated (electrophilic) alkylator species, chemoprotectants for the anthracyclines appear to complex with metal cofactors like iron, which are required for the production of cardiotoxicity. Several ethylenediaminetetraacetic-like agents have been evaluated, and a water-soluble piperazinyl derivative, ICRF-187, is currently undergoing clinical evaluation in patients receiving large cumulative doxorubicin doses. An initial clinical trial suggests that ICRF-187 can prevent doxorubicin-induced cardiomyopathy. As with mesna, ICRF-187 does not block the myelosuppressive or the antitumor effects of doxorubicin. Overall, these studies show that site-selective chemoprotection is now feasible for at least two major classes of anticancer agents. PMID- 1899490 TI - [Studies on the influence of air cavities during irradiation with high energy electrons]. AB - Radiation therapy of tumors is often performed with high energy electrons. In certain situations air cavities in the irradiation volume can change the dose distribution. The effects of air cavities on the dose distribution are investigated. The results calculated with a therapy planning system and measured in a phantom are described and compared with one another and with the literature. PMID- 1899492 TI - Splanchnic oxygen consumption in septic and hemorrhagic shock. AB - Oxygen consumption (VO2) is dependent on oxygen delivery (DO2) in septic shock. Local hypoxia with later secondary organ failure may develop, however, despite an often hyperdynamic circulation. The splanchnic organs seem to be of vital importance in this context. In experiments performed in pigs we compared total body VO2 and DO2 with oxygen consumption and delivery in the gastrointestinal organs and the liver in two different shock states: (1) septic shock induced by peritonitis (n = 6) and (2) hemorrhagic shock (n = 6). Another group of six animals not in shock served as controls. Total, gastrointestinal, and liver DO2 decreased in a similar pattern in both septic and hemorrhagic shock. Gastrointestinal and liver VO2 increased in sepsis, whereas it was unchanged in hemorrhage. In the later phase of sepsis, liver VO2, but not gastrointestinal VO2, again decreased, because liver oxygen extraction was almost total and liver DO2 decreased further. The development of flow-dependent liver hypoxia was reflected in a decrease in liver lactate turnover (increased liver lactate release) during late sepsis. Early hypoxia in the splanchnic region is suggested as a plausible mechanism behind the development of secondary organ failure, especially in sepsis. PMID- 1899491 TI - Interleukin-2-induced lung injury is mediated by oxygen free radicals. AB - Interleukin-2 therapy leads to respiratory dysfunction caused by increased vascular permeability. This study examines the role of oxygen-derived free radicals (OFR). Sheep (n = 6) with chronic lung lymph fistulae were given interleukin-2, 10(5) units/kg, as an intravenous bolus. The mean pulmonary artery pressure rose from 13 to 23 mm Hg (p less than 0.05) at 1 hour and remained elevated for 4 hours, although the pulmonary artery wedge pressure was unchanged at 4 mm Hg. Arterial oxygen tension fell from 88 to 77 mm Hg (p less than 0.05). Lung lymph flow rose from 2.2 to 6.4 ml/30 min (p less than 0.05) at 3 hours. This rise coincided with an increase in the lymph/plasma protein ratio from 0.67 to 0.77 (p less than 0.05) and lymph protein clearance from 1.5 to 4.4 ml/30 min (p less than 0.05), indicating increased lung microvascular permeability. Interleukin-2 led to transient increases in plasma thromboxane B2 from 168 to 388 pg/ml (p less than 0.05) and lung lymph thromboxane B2 from 235 to 694 pg/ml (p less than 0.05). The leukocyte count fell from 8156 to 4375/mm3 (p less than 0.05) primarily caused by a 78% drop in lymphocyte count. Platelet count declined from 292 to 184 X 10(3)/mm3 (p less than 0.05). Pretreatment with the hydroxyl radical scavenger dimethylthiourea, 1 gm/kg, intravenously, (n = 6) prevented the interleukin-2-induced increase in mean pulmonary artery pressure, lung lymph flow, lymph/plasma protein ration, lymph protein clearance, and thromboxane B2 levels in plasma and lung lymph. The arterial oxygen tension decreased from 85 to 80 mm Hg (p less than 0.05). The leukocyte count declined from 7854 to 6229/mm3 (p less than 0.05), but this was not as low nor as prolonged as the interleukin-2 group. Further, the decrease in platelet count was prevented (p less than 0.05). Interleukin-2 incubated with sheep or human leukocytes led to a dose-dependent increase in intracellular hydrogen peroxide production by neutrophils as measured by flow cytometry of dichlorofluorescein oxidation. These data indicate that interleukin-2 stimulates OFR generation and that OFR moderate the interleukin-2 induced increased lung permeability. PMID- 1899493 TI - Strontium toxicity in Drosophila melanogaster. AB - The Drosophila strains v;bw and Austin represent the extremes in resistance and sensitivity, respectively, to the toxic effects of CdCl2 in the diet. Using the six genotypes containing the possible combinations of the three main chromosomes for v;bw and Austin, we had shown previously that the gene(s) for cadmium resistance is on the X-chromosome. In this paper it is shown, using the same six genotypes, that the gene(s) for strontium resistance is on the second chromosome, as measured by LC50 values. PMID- 1899494 TI - Physiologic basis of endocrine therapy for prostatic cancer. AB - Advances in our understanding of hypothalamic-pituitary gonadal regulation have led to the development of pharmaceutical agents that produce a medically castrate state with minimal morbidity. The selection of the method for androgen ablation in a given patient with stage D adenocarcinoma of the prostate should be based on patient preference and on cost, because the therapeutic outcomes of medical castration and orchiectomy are equivalent. The addition of androgen receptor antagonists to a given patient's regimen should be made with the knowledge that the impact on the mortality rate is modest and the cost significant. Further manipulation of androgen production or action in patients with hormonally resistant cancer is unlikely to improve either the disease progression or the mortality rate. Research efforts should be focused on the development of effective chemotherapy for such disease. PMID- 1899495 TI - Total androgen ablation: American experience. AB - In conclusion, the intergroup study in the US, as well as preliminary results of the Anandron and leuprolide study, would support the view that combined androgen blockade is better than monotherapy in achieving clinical responses, prolonging the time to progression, and improving the survival rate. This improvement in survival rate is not a huge advance but is a step in the right direction. Future clinical trials are needed to evaluate newer methods to improve survival rates. The results also open up the possibility of employing this combined androgen blockade in earlier stages of prostate cancer in order to delay progression of the cancer and perhaps improve patient survival. Only carefully constructed clinical trials will be able to answer these questions. PMID- 1899496 TI - Cost-benefit analysis of pharmacologic erection program (PEP) versus penile prosthesis. AB - We compared the current dollar inclusive costs of the two most commonly implanted penile prostheses with our pharmacologic erection program (PEP). The inclusive cost of implantation for the inflatable penile prosthesis (IPP) is $9,000 and for the malleable penile prosthesis (MPP) $3,150. The inclusive cost of PEP at maximal dose and maximal frequency of use over a five-year period is $3,450. Penile prosthesis was found to be more cost-effective for the long-term treatment of younger impotent men, whereas in the elderly group the use of PEP over a limited time span may be equally or more cost-effective. PMID- 1899497 TI - High-resolution 3DFT MR imaging of the endolymphatic duct and soft tissues of the otic capsule. AB - This study compares the visualization of otic capsule anatomy by thin-section three-dimensional Fourier transformation (3DFT) MR imaging with that by high resolution CT. The osseous margins of the otic capsule are delineated by high resolution CT, while MR displays the soft-tissue structures. Routine two dimensional Fourier transformation (2DFT) spin-echo MR techniques have been limited by slice thickness and signal to noise. Previous longer TE 3DFT gradient echo MR images of the otic structures have been degraded by magnetic susceptibility effects, which limit spatial resolution and decrease signal to noise. These effects are especially prevalent in the otic capsule, where small soft-tissue structures interface with surrounding air and bone. We developed a high-resolution 3DFT MR technique to image five normal subjects. MR images were compared with high-resolution CT images of the same subjects. Axial, sagittal, and coronal 3DFT gradient-echo MR images with a short TR/TE and 15 degrees flip angle were acquired on a General Electric 1.5-T Signa unit using a 3-in. circular, receive-only surface coil. Axial, sagittal, and coronal 1.5-mm-thick contiguous high-resolution CT bone-algorithm images were obtained also. There was a high correlation between the MR and CT findings. The 3DFT MR images demonstrated significantly higher spatial resolution and soft-tissue detail than the high-resolution CT images did. For example, the endolymphatic duct was seen on twice the number of consecutive sagittal and axial MR slices. Other soft tissue otic capsule structures routinely seen on the 3DFT MR images included the entire facial nerve, membranous labyrinth including cochlea, and tensor tympani muscle. This study demonstrates a new high-resolution 3DFT MR technique for visualizing the soft-tissue microstructures of the otic capsule and achieves a level of spatial resolution beyond that possible with high-resolution CT. PMID- 1899498 TI - Contrast enhancement of the labyrinth on MR scans in patients with sudden hearing loss and vertigo: evidence of labyrinthine disease. AB - The sudden onset of hearing loss and vertigo presents a difficult diagnostic problem. We describe the finding of labyrinthine enhancement on MR images in five patients with sudden unilateral hearing loss or vertigo or both and correlate the MR findings with audiologic and electronystagmographic studies. All patients were studied with T2-weighted axial images through the whole brain, contrast-enhanced 3-mm axial T1-weighted images through the temporal bone, and enhanced T1-weighted sagittal images through the whole brain. Cochlear enhancement, on the side of hearing loss only, was found in all five patients. The presence of associated vestibular enhancement correlates with objective measures of vestibular function on the electronystagmogram. In two patients, the resolution of symptoms 4-6 months later correlated with resolution of the enhancement on gadopentetate dimeglumine-enhanced MR images. Two patients had luetic labyrinthitis. No labyrinthine enhancement was seen in a series of 30 control subjects studied with gadopentetate dimeglumine-enhanced MR using the same protocol. Labyrinthine enhancement in patients with auditory and vestibular symptoms is a new finding and is indicative of labyrinthine disease. While abnormalities on electronystagmograms and audiograms are nonspecific and indicate only a sensorineural problem, gadopentetate dimeglumine-enhanced MR may separate patients with retrocochlear lesions, such as acoustic neuromas, from those in whom the abnormal process is in the labyrinth or is intraaxial. This group of patients underscores the importance of identifying and commenting on the structures of the membranous labyrinth when evaluating MR studies of the internal auditory canal and the cerebellopontine angle in individuals with hearing loss. PMID- 1899499 TI - Technical note: mobile CT scanner gantry for use in the operating room. PMID- 1899500 TI - The neuroradiologist goes to the operating room. PMID- 1899501 TI - Technical note: enhanced MR-guided stereotaxic brain surgery with the patient under general anesthesia. PMID- 1899502 TI - Brainstem edema: an unusual complication of carotid cavernous fistula. PMID- 1899503 TI - MR imaging of pituitary dwarfism. AB - The purpose of this study was to determine whether the MR findings of idiopathic pituitary dwarfism correlated with a clinical history of perinatal abnormalities and abnormal levels of pituitary hormones. MR examinations of 18 patients with pituitary dwarfism were performed; these patients were divided into two groups: those with ectopic posterior lobes (group 1) and those with normal posterior lobes (group 2). Among the seven patients in group 1, MR showed hyperintense signal at the median eminence of the hypothalamus, which was regarded as the ectopic posterior lobe of the pituitary gland. The mean anteroposterior length and height of the pituitary gland in group 1 patients were significantly smaller than those dimensions in the normal control group; the pituitary stalk was not detected in three of seven patients. Six of seven patients were products of breech presentation with perinatal asphyxia. The peak serum growth hormone level was less than 5 ng/ml when assessed by insulin-induced hypoglycemia or the clonidine test. MR findings in the 11 patients with pituitary dwarfism and normal posterior lobes were normal except that the mean size of the pituitary gland was slightly smaller than that of normal controls. The clinical history of these patients was normal except for perinatal asphyxia in one case. Our findings in patients with pituitary dwarfism, with or without an ectopic posterior pituitary lobe suggest that the ectopic lobe, visualized as a bright spot at the median eminence of the hypothalamus, may be common when pituitary dwarfism follows perinatal anoxic/ischemic episodes. PMID- 1899504 TI - MR of the temporal bone. PMID- 1899505 TI - Subcutaneous sacrococcygeal myxopapillary ependymoma: CT and MR findings. PMID- 1899506 TI - Aseptic meningitis complicating iotrolan myelography. PMID- 1899507 TI - Tentorial traversal by ependymoblastoma. PMID- 1899508 TI - Contrast-enhanced MR imaging of Tolosa-Hunt syndrome: a case report. PMID- 1899509 TI - CT of infantile myofibromatosis of the orbit with intracranial involvement: a case report. PMID- 1899510 TI - Anomalous origin of the posterior inferior cerebellar artery from the posterior meningeal artery. PMID- 1899511 TI - Anomalous branching of the left common carotid artery with associated atherosclerotic changes: a case report. PMID- 1899512 TI - MR appearance of postoperative foreign body granuloma: case report with pathologic confirmation. PMID- 1899513 TI - Eighth nerve herpetic neuritis and contralateral rhombencephalitis and mesencephalitis on contrast-enhanced MR imaging. PMID- 1899515 TI - Association of deep white matter infarction with chronic communicating hydrocephalus: implications regarding the possible origin of normal-pressure hydrocephalus. AB - The coexistence of cerebrovascular disease leading to deep white matter infarction and normal-pressure hydrocephalus has been noted previously in clinical studies, as both diseases can present with the triad of gait disturbance, dementia, and incontinence. The purpose of this MR study was to determine if the two diseases demonstrated a statistical association. Evidence of patchy periventricular hyperintensity representing presumed deep white matter infarction was sought in 20 patients shunted for normal-pressure hydrocephalus and in 35 additional consecutive patients with clinical symptoms and MR findings consistent with normal-pressure hydrocephalus. Deep white matter infarction was also sought in 62 consecutive age-matched control subjects. There was a statistically significant (p less than .001) higher association (58%) of marked infarction in the 55 patients with normal-pressure hydrocephalus than in the age matched controls (24%). MR findings of communicating hydrocephalus (ventriculomegaly and increased aqueductal CSF flow void) were sought in 78 consecutive patients with presumed deep white matter infarction, and the degree of severity of the two diseases was also found to be statistically significant (p less than .05). In view of this association, the possibility that the two diseases are related was considered. A potential mechanism is discussed whereby deep white matter infarction leading to decreased periventricular tensile strength could result in communicating hydrocephalus. It is plausible that normal pressure hydrocephalus may result from a number of different insults to the brain. PMID- 1899514 TI - Sinonasal psammomatoid ossifying fibromas: CT and MR manifestations. AB - Five cases of pathologically proved psammomatoid ossifying fibromas of the sinonasal area are presented. All five cases were examined by CT and in three cases MR imaging was performed before and after injection of gadopentetate dimeglumine. The lesions were located in the sphenoethmoidal area and extended over the nasal cavity or orbit in four cases. In one case, the lesion occurred at the perpendicular plate of the ethmoid bone with preservation of the ethmoidal sinus. On CT, all the lesions were expansile and circumscribed by a thick bony wall. Internal septations of bone density (four cases) or enhancing soft-tissue density (one case) were seen and internal content was low in density in all but one from which blood was aspirated. On MR, the bony walls were isointense with gray matter on T1-weighted images and were seen as areas of low intensity on T2 weighted images. The lesions significantly enhanced after injection of contrast material. A well-circumscribed multiloculated expansile mass with a thick wall of bone density on CT scans and enhancement of this area on postcontrast MR images is strongly suggestive of psammomatoid ossifying fibroma. PMID- 1899516 TI - White matter lesions and normal-pressure hydrocephalus: Binswanger disease or Hakim syndrome? PMID- 1899517 TI - Chronic communicating hydrocephalus and periventricular white matter disease: a debate with regard to cause and effect. PMID- 1899518 TI - MR imaging of the brain in Fukuyama-type congenital muscular dystrophy. PMID- 1899519 TI - MR findings in the brains of compressed-air tunnel workers: relationship to psychometric results. AB - Cranial MR imaging was performed in 30 subjects who had been involved in compressed-air tunnel projects in and around Milwaukee, WI. Nineteen of these subjects had been exposed to various degrees of hyperbaric air as calculated by an exposure index (average PSI pressure gauge multiplied by the number of years exposed), while 11 of the subjects were age-matched controls who belonged to the same labor union but had not been exposed to hyperbaric air. All MR scanning was done on a 1.5-T unit, and axial, sagittal, and coronal T1, proton density, and T2 weighted images were obtained. Ventricular size was measured objectively. Foci of increased T2 intensity within deep white matter tracts were evaluated as to number and location, and psychometric testing was performed on both groups to exclude preexisting organic brain disease. The 19 subjects in the experimental group had a statistically higher number (p = .05) of white matter lesions (more than 152) than the control group (22 lesions), and 37% of the experimental group had more than 20 white matter lesions each (seven of 19 subjects) while only 18% of the control group had 10 or 11 lesions each. The experimental group had a five times higher risk than the control group of having high-grade lesions, and a high statistical correlation (p = .02) was found between the number and severity of lesions in the experimental group as compared with the control group when linear trend analysis was performed. No correlation was found between exposure index, MR grade or number, or aseptic necrosis. Ventricular size was normal in all subjects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1899521 TI - Sydenham chorea: MR manifestations in two cases. PMID- 1899520 TI - MR appearance of hypertrophic olivary degeneration after contralateral cerebellar hemorrhage. PMID- 1899522 TI - Chorea: whither comest it? PMID- 1899523 TI - Pontine hydatid cyst in association with an acoustic neurinoma: MR appearance in an unusual case. PMID- 1899524 TI - MR imaging of cerebral gumma. PMID- 1899525 TI - Coexistent intra- and extracranial mass lesions: an unusual manifestations of histiocytosis X. PMID- 1899526 TI - Xenon-enhanced CT of the brain: effect of flow activation on derived cerebral blood flow measurements. AB - The errors associated with derivation of cerebral blood flow values by the xenon enhanced CT method have been evaluated through computer simulations as a function of flow-activation patterns and different scanning protocols. The results of this study indicate that actual flow activation during inhalation increases the derived flow values in a systematic way. Compared with the errors introduced by CT noise and/or variations in scanning protocols, flow activation introduces relatively small errors in the derived flow value when the washin technique is used. PMID- 1899527 TI - Accuracy of xenon CT measurement of cerebral blood flow. PMID- 1899528 TI - The role of xenon CT measurements of cerebral blood flow in the clinical determination of brain death. AB - The demonstration of absent blood flow to the brain is often used as a confirmatory test of brain death. Traditionally, cerebral angiography and dynamic radionuclide brain scanning have been used for this purpose. Recently, xenon CT cerebral blood flow techniques have been developed and applied to a wide variety of clinical problems, including the confirmation of brain death. We report our experience with xenon CT studies performed over a 7-year period (1983-1989) in 30 patients with brain injuries. These patients met clinical criteria for brain death within 24 hr of the study. Twenty patients had average global flow values of less than 5 ml/100 ml/min. Seven patients demonstrated mixed flow patterns, whereby large areas of brain showed flow values of less than 5 ml/100 ml/min and residual pockets of flow greater than 5 ml/100/ml/min. Globally symmetric normal to hyperemic flows were seen in three patients. Our study suggests that the demonstration of average global flows of less than 5/ml/100 ml/min is confirmatory of brain death. Demonstration of persistent flow to the entire brain or regions of the brain is not diagnostic of brain death but also does not exclude such an outcome in patients with severe brain injuries. Xenon-derived flow information may be clinically useful in determining the patient's prognosis and in counseling the patient's family. PMID- 1899529 TI - Ossifying fibromyxoid tumor. Something new to mull over. PMID- 1899530 TI - A field evaluation of the Coulter STKS. AB - The performance of the Coulter STKS (Coulter, Hialeah, FL) was evaluated in a busy computerized teaching hospital laboratory. The STKS was compared with a Coulter S Plus IV and manually performed 400 white blood-cell differentials. The measured blood-count parameters (i.e., white blood cells [WBCs], red blood cells [RBCs], hemoglobulin [Hb], mean corpuscular volume [MCV], and platelets [PLTs]), compared very well between the two aperture impedance-based systems; precision, linearity, and lack of carryover were excellent. The STKS WBC differential (DIFF), derived from a combination of aperture impedance, aperture conductance, and laser light scatter, also was precise; linear and carryover were insignificant. The DIFFs (n = 424) compared well to the manual WBC differentials, with r values of 0.97, 0.97, 0.73, and 0.86 for neutrophils, lymphocytes, monocytes, and eosinophils, respectively. The DIFF and Suspect Flagging system produced 6.2% false negatives and 2.6% false positives when compared with the manual technique. These were further investigated and discussed. STKS DIFFs were stable for 18 to 24 hours in normal samples anticoagulated with K2EDTA and stored at 20 degrees C prior to analysis. Storage in the same anticoagulant at 4 degrees C and immediate aspiration preserved the DIFF analysis for considerably longer than 24 hours. These performance characteristics make the STKS a significant advancement in automated hematology. PMID- 1899531 TI - Role of prostaglandins in pregnancy-induced hypertension. AB - Enzymes involved in prostaglandin I2 (PGI2) and thromboxane A2 (TXA2) synthesis were studied in maternal and fetal platelets and venous endothelium from normotensive pregnant controls (n = 70), women with mild preeclampsia (MP, n = 45), and severe preeclampsia (SP, n = 34). Activities of phospholipase A2 (PHA2), cyclooxygenase (PGHS), and PGI2 synthetase (PGIS) or TXA2 synthetase (TXAS) were determined in platelets and in endothelial cells. The PGHS enzyme was studied further by immunoblot methodology. In maternal platelets: Vmax (per 10(-10) mol/mg protein) and Michaelis-Menten constant (Km) (10(-7) mol, mean +/- SEM) of PHA2 were 3.0 +/- 0.8, 3.0 +/- 0.7, and 31.7 +/- 10.9* maximum velocity (Vmax) and 1.8 +/- 0.3, 2.0 +/- 0.8, and 0.8 +/- 0.2 (Km) in normal control (NC), mild preeclampsia (MP), and severe preeclampsia (SP), respectively (*P less than 0.05 against NC). The apparent overall PGHS plus TXAS activity was 10.2 +/- 1.8, 23.8 +/- 7.1, and 68.8 +/- 18.8* (Vmax) and 3.2 +/- 1.3, 5.4 +/- 1.4, and 6.9 +/- 1.2* (Km, *P less than 0.05 against NC). TXA synthesis in fetal platelets demonstrated PHA2 activity of 6.4 +/- 1.4, 12.0 +/- 1.3, and 17.2 +/- 3.2* (Vmax) and 3.5 +/- 0.9, 2.2 +/- 1.5, and 0.7 +/- 0.3* (Km, *P less than 0.05 against NC), respectively, whereas an apparent overall PGHS plus TXAS activity was 18.5 +/- 2.8, 87.5 +/- 12.5*, and 3.6 +/- 0.1* (Vmax) and 4.8 +/- 1.0, 8.8 +/- 1.2, and 0.8 +/- 0.3* (Km, *P less than 0.05 against NC).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1899532 TI - Utility of immunofluorescence of urine sediment for identifying patients with renal disease due to monoclonal gammopathies. AB - Immunofluorescence (IF) of urine sediment with antisera to light-chain immunoglobulins (LC) was used for patients with renal disease due to various monoclonal gammopathies. Urinary casts and/or masses from 20 of 27 patients (74%) of this group stained predominantly for one or another of the two LC, but from none of the 25 controls, who all had renal diseases other than monoclonal gammopathies. In all but one patient with monoclonal gammopathy the more intensely staining LC in the urine sediment was the same as that found in the paraprotein. For 68.7% of patients, the prevailing LC in urinary casts was the same as that prevailing in the casts of the renal biopsies. The sensitivity of IF of urine sediment for identifying patients with plasma cell dyscrasias was 74%, the specificity 100%, and the accuracy 86.5%. The positive predictive value was 100% and the negative predictive value was 78%. Globally, urine sediment IF was more sensitive than serum or urine electrophoresis (74% v 63% and 66.6%), but less than serum or urine immunoelectrophoresis (74% v 85%). In light-chain deposition disease, a disorder in which there are often no definite symptoms, urine sediment IF was more sensitive than both traditional methods. We conclude that IF of urine sediment is a useful test to identify patients with renal disease associated with monoclonal gammopathies. PMID- 1899533 TI - The hemodynamic effects of intubation during nitroglycerin infusion in severe preeclampsia. AB - The effectiveness of intravenous nitroglycerin infusion in lowering maternal blood pressure and in blunting the hemodynamic responses to endotracheal intubation was evaluated in six primigravid women with severe preeclampsia. Monitoring consisted of continuous electrocardiogram monitoring, arterial cannulation, and flow-directed pulmonary arterial catheterization in each patient. All patients underwent oxytocin induction of labor and crystalloid and/or colloid expansion to produce a pulmonary capillary wedge pressure of 10 to 15 mm Hg and a colloid osmotic pressure of greater than 17 mm Hg. Intravenous nitroglycerin was administered before induction of general anesthesia. The hemodynamic effects associated with endotracheal intubation revealed a change in the heart rate from 104 +/- 10 to 133 +/- 17 beats/min, an increase in mean arterial pressure from 134 +/- 12 to 164 +/- 32 mm Hg, and an increase in systemic vascular resistance from 1262 +/- 342 to 1351 +/- 259 dynes-sec-cm-5 that was accompanied by a small change in the cardiac index from 4.5 +/- 1.2 to 4.5 +/- 0.9 L.min-1.m-2. PMID- 1899535 TI - Rh immune globulin prophylaxis for threatened abortions. PMID- 1899534 TI - The action of nitric oxide in the perfused human fetal-placental circulation. AB - Nitric oxide is thought to be the endogenous endothelium-derived relaxing factor. We investigated the effects of compounds that either generate nitric oxide intracellularly or inhibit its action on the vasculature of the human placental villus. Addition to perfusion medium of methylene blue (10(5) mol/L), which is an inhibitor of activation of guanylate cyclase by nitric oxide, significantly increased perfusion pressure of the fetal-placental circulation over a range of flow rates (1 to 10 ml/min) compared with the perfusion pressures seen in the absence of methylene blue. This suggests basal release of nitric oxide may contribute to maintenance of resting vascular tone. Both glyceryl trinitrate (10( 9) to 5 x 10(6) mol/L) and S-nitroso-N-acetylpenicillamine (10(-8) to 10(-4) mol/L), which generate nitric oxide intracellularly, were able to significantly vasodilate the fetal-placental circulation preconstricted with the thromboxane mimetic U46619 (1 to 5 x 10(-8) mol/L) in a concentration-dependent manner. These compounds had no effect in the absence of the vasoconstrictor. Thus it appears that the placental villus tree has the ability to both generate and respond to nitric oxide. PMID- 1899536 TI - Endoscopic laser-assisted lacrimal surgery. AB - Since Sept. 1, 1989, we have successfully performed 20 video-endoscopic, transnasal, laser-assisted lacrimal procedures on 18 patients ranging in age from 3 to 88 years. This technique avoided a cutaneous scar and caused less surgical trauma and bleeding than that seen in conventional lacrimal surgery, which shortened postoperative recovery time and lessened postoperative pain. With minor modifications in surgical technique, both dacryocystorhinostomy and conjunctivodacryocystorhinostomy were performed with either the potassium titanyl phosphate or carbon dioxide lasers. The use of the video endoscope allowed laser surgery to be performed across a broad range of intranasal structural variations and provided an excellent medium for teaching this new technique. PMID- 1899537 TI - Tissue plasminogen activator treatment of experimental subretinal hemorrhage. AB - To determine if tissue plasminogen activator, a clot-specific fibrinolytic agent, could eventually be used to assist in the clearance or removal of subretinal hemorrhage, we studied the effect of subretinal injections of tissue plasminogen activator, autologous blood, balanced salt solution, and the combination of either tissue plasminogen activator or balanced salt solution after subretinal injection of autologous blood on retinal morphologic characteristics and clearance of subretinal hemorrhage in the albino rabbit. No morphologic evidence of tissue plasminogen activator toxicity was found in the rabbit retina at a dose of 25 to 50 micrograms/0.1 ml. Subretinal hemorrhage cleared faster after subretinal injection of tissue plasminogen activator when compared to balanced salt solution (P = .0005) but did not completely prevent overlying retinal degeneration. Both tissue plasminogen activator and balanced salt solution were found to decrease the toxic effects of subretinal blood on the morphologic characteristics of the rabbit retina, and this effect can be explained at least partly by dilution of the subretinal blood. PMID- 1899538 TI - Intracameral tissue plasminogen activator for resolution of fibrin clots after glaucoma filtering procedures. PMID- 1899540 TI - Juvenile ceroid lipofuscinosis. Evidence for methylated lysine in neural storage body protein. AB - Juvenile ceroid lipofuscinosis, or Batten disease, is a hereditary disorder characterized by progressive visual loss, seizures, cognitive and psychomotor deterioration, and early death, usually between 15 and 35 years of age. Individuals with this disease have massive deposits of autofluorescent inclusion bodies in cells of most tissues. The accumulation of these intracellular deposits suggests that juvenile ceroid-lipofuscinosis is a storage disease resulting from the inability of cells to metabolize some normal cellular constituent. It has been reported that the storage material is largely protein, much of which is a specific mitochondrial protein that apparently is not properly metabolized in subjects with Batten disease. The storage bodies were partially purified from the retinas of two siblings who died as a result of juvenile ceroid lipofuscinosis, as well as from the cerebral cortex of an unrelated individual with this disorder. Chromatographic analysis of storage body protein acid hydrolysates indicated that they contained a large amount of the modified amino acid epsilon-N trimethyllysine. The abundance of this amino acid in the storage protein suggests that the disease may result from excessive methylation or from a failure to demethylate intermediate forms of the stored proteins. Acid hydrolysis also solubilized a fluorescent component from the retinal storage material, suggesting that the stored protein has a bound fluorescent adduct. PMID- 1899539 TI - Absence of bcl-2 major breakpoint region and JH gene rearrangement in lymphocyte predominance Hodgkin's disease. Results of Southern blot analysis and polymerase chain reaction. AB - Recent evidence suggests that nodular lymphocyte predominance Hodgkin's disease (NLPHD) is a distinct entity that may be related to progressively transformed germinal centers, abnormal B-lymphoid hyperplasia, and low-grade B-cell lymphoma. bcl-2 is a marker for the translocation t(14;18)(q32;q21), which occurs in most follicular-derived B-cell lymphomas. Eleven cases of NLPHD and 19 cases of Hodgkin's disease of nodular sclerosis (NSHD) and mixed cellularity (MCHD) type were analyzed for immunoglobulin JH gene rearrangement. bcl-2 translocation was determined with Southern blot analysis and the polymerase chain reaction using biotin labeled probes to the major breakpoint region and the alkaline phosphatase reaction. All cases of NLPHD were negative for JH gene rearrangement and bcl-2 translocation. Cases of NSHD and MCHD were similarly negative for bcl-2, although three cases exhibited clonal JH gene rearrangements. These results confirm that a clonal B-cell population is not detected in NLPHD. Cases of NLPHD differ from most low-grade follicular B-cell lymphomas in that they lack bcl-2 gene rearrangement and t(14;18) translocation at the major breakpoint region. PMID- 1899541 TI - Renal sympathetic nerve and hemodynamic responses to captopril in conscious dogs: role of prostaglandins. AB - The angiotensin converting enzyme inhibitor captopril has been shown to cause resetting of the arterial baroreflex to a lower pressure without a change in gain. The present study was conducted to determine whether captopril altered the relationship between arterial pressure, heart rate, and renal sympathetic nerve activity in conscious quietly resting dogs. Fourteen instrumented dogs were given 2 mg/kg iv of captopril; 10 min later postcaptopril measurements were made. Six of the fourteen dogs were pretreated with cyclooxygenase inhibitor (indomethacin or meclofenamate) before administration of captopril. Renal nerve activity and hemodynamics were measured in a final group of eight dogs in which arterial pressure was lowered with a graded infusion of sodium nitroprusside. Captopril caused a small but significant decrease in arterial pressure. This decrease in arterial pressure was accompanied by a significant increase in heart rate; however, renal sympathetic nerve activity was significantly reduced. In contrast, dogs receiving nitroprusside exhibited an increase in both heart rate and renal sympathetic nerve activity in response to similar decreases in arterial pressure. Dogs that received cyclooxygenase inhibitor showed reduced arterial pressure in response to captopril, increased heart rate, and increased renal sympathetic nerve activity. This study is the first to report a decrease in sympathetic nerve activity in response to captopril in an awake chronically instrumented animals. These data suggest that captopril's ability to augment prostaglandin synthesis is responsible for the observed sympathoinhibition. PMID- 1899542 TI - Reactive oxygen metabolite scavengers decrease functional coronary microvascular injury due to ischemia-reperfusion. AB - The role of reactive oxygen metabolites in ischemia-reperfusion coronary microvascular injury is unclear. To investigate this problem, we tested the effects of the reactive oxygen metabolite scavengers superoxide dismutase (SOD) and dimethylthiourea (DMTU) on ischemia-reperfusion-induced coronary microvascular dysfunction. As an index of vascular function, we assessed microvascular permeability with a double radioisotope protein leak index (PLI) method. Anesthetized dogs underwent 60 min of ischemia via left anterior descending (LAD) occlusion followed by 60 min of reperfusion. Untreated animals (n = 7) received saline. SOD-treated animals (n = 6) received 140 U.kg-1.min-1 (6.6 mg.kg-1.min-1) bovine SOD throughout ischemia and reperfusion. DMTU-treated animals (n = 5) received a 500 mg/kg bolus 30 min before ischemia. At the beginning of reperfusion, radiolabeled autologous protein (113mIn transferrin) and red blood cells (99mTc) were given intravenously for the assessment of permeability. In untreated dogs, ischemia-reperfusion increased the PLI of ischemic (flow less than 20 ml.min-1.100 g-1) myocardium more than threefold compared with that of nonischemic (flow greater than 100 ml.min-1.100 g-1) myocardium (ischemic-to-nonischemic PLI ratio = 3.49 +/- 0.48). SOD reduced the PLI of ischemic myocardium by 45% and DMTU reduced it by 66% (PLI = 9.25 +/- 1.30, 5.04 +/- 1.18, and 3.16 +/- 0.94, untreated, SOD, and DMTU, respectively). The PLI was increased proportional to the regional severity of ischemic blood flow. Both SOD and DMTU reduced the increase in protein leak at all levels of regional ischemic blood flow. Neither SOD nor DMTU increased regional myocardial blood flow to the occluded LAD zone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1899543 TI - SCN lesions block responses to systemic melatonin infusions in Siberian hamsters. AB - The role of the suprachiasmatic nuclei (SCN) in the response to short-day melatonin (MEL) signals was examined in long-day-housed pinealectomized (PINX) Siberian hamsters. Five- or ten-hour MEL infusions that mimicked the peak nocturnal durations of serum MEL levels in long or short days, respectively, or control saline infusions were given for 5 wk. Half the hamsters in each infusion group also received bilateral electrolytic SCN lesions. The 10-h MEL infusions reduced testes weight, body and fat pad weights, and serum prolactin (PRL) and follicle-stimulating hormone (FSH) concentrations in unoperated controls. These short-day-type effects were blocked by SCN lesions, which often produced hyperprolactinemia. Circadian rhythms of locomotor activity were disrupted or sparse in hamsters with lesions in or near the SCN. In a second experiment, 5 wk of long-day-like, short-duration (5-h) MEL infusions were administered to hamsters that had been PINX after 8 wk of short-day exposure. Control hamsters given 5-h MEL infusions, but not 10-h MEL or saline infusions, exhibited testicular growth and increased serum PRL levels. Hamsters with SCN lesions showed similar responses, regardless of the duration or type of infusion. Although the blockade of 10-h MEL infusion-induced testicular regression by SCN lesions in experiment 1 may have been due to stimulation of the testes by PRL, it is unlikely that the hyperprolactinemia accounted for the ability of SCN lesions to block effects of 10-h MEL infusions on fat pad and body weights. Therefore, the SCN and/or neighboring structures may participate in the response to short day MEL signals in Siberian hamsters. PMID- 1899546 TI - Streptokinase and recombinant tissue plasminogen activator (rt-PA) are equally effective in treating acute myocardial infarction. AB - In recent trials, patients with myocardial infarction who received either recombinant tissue-type plasminogen activator (rt-PA) or streptokinase showed essentially no difference in the amount of myocardial salvage, in mortality reduction, or in the incidence of bleeding complications. These findings thus failed to fulfill the expectation that rt-PA would be twice as effective as streptokinase as a thrombolytic agent. The basis for this mistaken prediction was an unfortunate overemphasis on an inadequate surrogate endpoint, namely, the patency or reperfusion rate at 90 minutes after the start of therapy. Using the 90-minute patency or reperfusion rate as an endpoint has several serious limitations. First, it is an observation made at only one point in time during a dynamic process that may change even during the infusion proper. Second, a single view at 90 minutes completely disregards the possibility of subsequent reocclusion which often occurs within 1 hour after treatment. Third, an image at 90 minutes is more a reflection of the speed of thrombolysis than of whether lysis will eventually occur; the pace of clot lysis depends on both the agent used and the age of the thrombus. Fourth, lysis at 90 minutes is of minimal relevance for myocardial salvage unless observed within the time frame when infarction size can be limited significantly, which is generally less than 4 hours between symptom onset and the time that reperfusion is accomplished. Fifth, a stable state of vessel patency is meaningful for mortality reduction even if stabilization occurs after completion of the infarction. Such "late," but lasting, patency is a critical component of the "open vessel" principle and explains, at least in part, the survival benefit that accrues to patients treated even 24 hours after the onset of symptoms. There is currently no evidence that rt PA has a more beneficial effect on survival or function than does streptokinase or any other plasminogen activator used in treating acute myocardial infarction; nor is there any evidence that patients who receive rt-PA therapy show a decreased incidence of bleeding complications compared with those who receive streptokinase, despite the relative fibrinogen-sparing attribute of rt-PA. Given the poor predictive value of the 90-minute angiogram for ultimate clinical advantage of one agent over another, studies that are limited to this endpoint are of marginal use in evaluating treatment regimens used in mortality studies. The best evidence to date indicates that streptokinase and rt-PA are of equivalent value for survival after acute myocardial infarction, a conclusion that can be justifiably challenged only with a valid mortality study. PMID- 1899545 TI - Combined treatment with lithium and carbamazepine. PMID- 1899544 TI - Suprachiasmatic and paraventricular control of photoperiodism in Siberian hamsters. AB - The effects of lesions of the suprachiasmatic (SCN) and paraventricular nuclei (PVN) of the hypothalamus on photoperiodic responses were examined in adult Siberian hamsters. SCN lesions reduced nocturnal water intake in long days, whereas PVN lesions increased body weight and food intake in both short and long days. SCN or PVN lesions blocked short-day-induced decreases in body, fat pad, and testes weights and in food intake. Serum prolactin (PRL), but not follicle stimulating hormone, levels were increased. The distribution of immunostained neurons and fibers for gonadotropin-releasing hormone (GnRH), beta-endorphin, arginine vasopressin (AVP), and vasoactive intestinal polypeptide (VIP) resembled that of other rodent species. Short-day exposure reduced AVP staining in lateral septum, medial amygdala, and bed nucleus of the stria terminalis but not in the PVN of the thalamus or the SCN. Short-day-exposed hamsters had fewer beta endorphin-positive arcuate nucleus cells and tended to have fewer GnRH-positive preoptic cells than long-day controls. VIP staining was unaffected by photoperiod. Most day length effects on immunostaining were eliminated by either lesion. These results establish the importance of the SCN and PVN in the photoperiodic control of several seasonal responses in Siberian hamsters. PMID- 1899547 TI - [Cross-resistance of HO-221 and various antitumor agents in sublines of mouse leukemia]. AB - HO-221, N-[4-(5-bromo-2-pyrimidinyloxy)-3-chlorophenyl]-N'-(2- nitrobenzoyl) urea is a new benzoylphenylurea derivative. The compound exhibits significant antitumor effects against various animal tumors, and was especially effective against the solid tumors implanted subcutaneously. HO-221 inhibits DNA polymerase alpha activity strongly in vitro. In this study, we examined the cross-resistance of HO-221 to various antitumor agents using sublines of mouse leukemia. HO-221 showed antitumor effects in mice bearing L 1210 or P 388 leukemia resistant to 10 antitumor agents, DM (daunomycin), MMC (mitomycin C), CDDP (cisplatin), 5-FU (5 fluorouracil), Ara-C (cytosine arabinoside), MTX (methotrexate), CPA (cyclophosphamide), CQ (carboquone), ADM (adriamycin) and VCR (vincristine), respectively. These antitumor agents were also effective in P 388 leukemia resistant to HO-221 (P 388/HO-221). Furthermore, CDDP- and MMC-resistant sublines showed a collateral sensitivity to HO-221 in vivo. The grow the inhibitory effects were also noted in vitro in ADM-, CDDP- and MMC-resistant cells by HO 221. However, the in vitro experiments didn't show such collateral sensitivity on the resistant sublines. These results suggest that there is no cross-resistance between HO-221 and other known antitumor agents, and that HO-221 seemed to be worth for evaluating clinical usefulness. PMID- 1899548 TI - [A clinical study of vitamin A concerning auxiliary chemotherapies after operation of gastric cancer]. AB - A comparative clinical study was conducted with an addition of vitamin A added to the auxiliary chemotherapies after surgical operation of gastric cancer. The OK 432 + MMC + Tegafur therapy (hereafter referred to as Group A) and the OK-432 + MMC + Tegafur + vitamin A therapy (Group B) were administered. The results were as follows. 1) The survival rate was slightly higher in Group B, although there was no significant difference between the two. 2) As to the rate of recurrence, it was significantly lower in Group B (p less than 0.05). The results above have suggested that additional vitamin A to the auxiliary chemotherapies after operation of gastric cancer can possibly be lower the recurrence rate, contributing to the prolongation of life. PMID- 1899550 TI - [Multihospital randomized study on pre- and post-operative adjuvant chemotherapy for colorectal cancer (Part 2)]. AB - Prior to surgery, 400 mg/day of UFT was administered for seven days to 86 patients with colorectal cancer. After surgery, the survival rate and side effects of the MMC only group (group A) and the MMC + UFT group (group B) were investigated. The two year survival rate for all cases was 79.8% for group B as opposed to 67.1% for group A. The two year survival rate for cases of histological curative resection were 80.0% for group A and 91.4% for group B, but the difference was not significant. There were few side effects in either group, and a significant difference in the incidence was not observed. Based on the above, MMC combined with UFT, as adjunctive chemotherapy for colorectal cancer, is considered to be a safe and effective treatment. PMID- 1899549 TI - [Treatment of gastric cancer patients with peritoneal metastasis by continuous hyperthermic peritoneal infusion with mitomycin C and cisplatin]. AB - Following the resection of its primary lesion, continuous hyperthermic peritoneal perfusion (CHPP) with anticancer drug (mitomycin C, cisplatin) containing warmed physiological saline was performed on gastric cancer having peritoneal dissemination, and the effect of CHPP was examined by second look operation (SLO). The subjects were 41 cases of gastric cancer with peritoneal dissemination but without hepatic metastasis, which we have experienced in the past 7 years. The prognosis of these CHPP-treated cases was such that 50% survival period, 3 year survival rate and 5 year survival rate were 398 days, 28.5 and 12%, respectively. Comparison of the effects of CHPP by SLO revealed remarkable diminution of the peritoneal dissemination in 7 (44%) of 16 cases and disappearance of the ascites with a single course of CHPP in 7 of ascitic cases. Long-term survival (greater than 3 years) was noted in 4 of the CHPP-treated cases. Side effects were renal insufficiency, leukopenia and small intestinal perforation in 2(5), 2(5) and 1 cases (2%), respectively. The above results suggested the effectiveness of CHPP for the treatment of gastric cancer having peritoneal dissemination. PMID- 1899551 TI - Immediate enteral feeding in burn patients is safe and effective. AB - Recent animal studies indicate that immediate enteral feeding may be beneficial in patients with major burns. Yet, largely because of the fear of complications, immediate enteral feeding is not commonly performed in patients with major burns until after the resuscitation period. The purpose of this study was to evaluate the safety and efficacy of immediate enteral tube feedings in patients with burns larger than 20% of their body surface area. The daily intake of enteral feedings begun immediately (less than 6 hours) after burn was measured during the first 7 days after burn in 106 consecutive patients with a mean +/- SD burn size of 40% +/- 21%. The incidence of complications related to enteral feeding was low; aspiration pneumonia did not occur. Vomiting was the major complication observed and occurred 21 times in 16 patients during the 745 study days (2.8% daily incidence). The mean number of calories absorbed enterally increased daily and met the patient's calculated resting energy expenditure (REE) on day 3 after burn (99% +/- 7% REE). The results of this study indicate that immediate enteral feeding is a safe and effective method of delivering nutritional support to burn victims with major burns. PMID- 1899553 TI - Diltiazem-induced psychosis and a possible diltiazem-lithium interaction. AB - Calcium channel blockers are being used increasingly for a variety of cardiovascular problems. Diltiazem hydrochloride, a benzothiazepine derivative, has been reported to have a low incidence of adverse side effects. We report a case of acute psychosis associated with the use of diltiazem in a patient receiving lithium carbonate therapy. Both diltiazem hydrochloride and lithium carbonate have calcium antagonist effects in the central nervous system, and we review their mechanisms of action. A possible synergistic drug interaction between diltiazem and lithium is reported. PMID- 1899552 TI - An acute disseminated coagulopathy-vasculopathy associated with the antiphospholipid syndrome. PMID- 1899554 TI - Association between the acquired immunodeficiency syndrome and infection with Salmonella typhi or Salmonella paratyphi in an endemic typhoid area. AB - Eight cases of typhoid and paratyphoid fever were identified during a 4-year period in a cohort of 117 patients who were positive for human immunodeficiency virus in Lima, Peru. Asymptomatic patients with human immunodeficiency virus infection and patients with the lymphadenopathy syndrome had a typical clinical presentation and response to therapy. Patients with the acquired immunodeficiency syndrome who were culture positive for Salmonella typhi or Salmonella paratyphi presented with fulminant diarrhea and/or colitis; the two patients for whom at least 2 months of follow-up were available relapsed. In our cohort there were 0.06 cases of typhoid or paratyphoid per patient year of observation; this rate is approximately 60 times that in the general population in Lima, and 25 times that in the 15- to 35-year-old age group. Our data indicate that patients who are positive for human immunodeficiency virus are at significantly increased risk for infection with S typhi and S paratyphi, and suggest that the clinical presentation of these diseases in patients with the acquired immunodeficiency syndrome differs from that seen immunocompetent hosts. PMID- 1899555 TI - Effect of lupus anticoagulants on the activated partial thromboplastin time. Results of the College of American Pathologists survey program. AB - Lupus anticoagulants are antibodies that interfere with in vitro phospholipid dependent coagulation reactions. In vivo, they have been associated with a variety of thromboembolic problems. Samples from patients with lupus anticoagulants were included in the 1986 and 1987 College of American Pathologists proficiency survey program. Participant performance on these samples demonstrated significant variation in the responsiveness of different activated partial thromboplastin reagents to lupus anticoagulants. The level of factor VIII in these samples reported by the participants also varied with the reagent used. Follow-up studies demonstrated striking reagent-dependent differences in the dilutional effect on apparent factor VIII, IX, XI, and XII activity. These results point out the importance of selecting sensitive and responsive reagents for appropriate identification of lupus inhibitors. In addition, the results indicate that the choice of reagent used for factor assays can affect the apparent factor activity as well as whether a dilutional effect is noted when a lupus anticoagulant is present in the test sample, an important consideration when trying to distinguish a lupus anticoagulant from a specific factor inhibitor. PMID- 1899556 TI - Gold-associated lymphadenopathy in a patient with rheumatoid arthritis. Histologic and scanning electron microscopic features. AB - The histologic features of adenopathy associated with intramuscular injections of gold sodium thiomalate in a woman with rheumatoid arthritis are presented. We believe that the light microscopic features of the above process are sufficiently distinctive that a diagnosis of gold-associated lymphadenopathy could be rendered. A review of the literature revealed no descriptions of the light microscopic appearance of gold in lymph nodes. In this case, the diagnosis of gold-associated lymphadenopathy was confirmed by scanning electron microscopic studies. PMID- 1899557 TI - Effect of endogenous nitric oxide on mitochondrial respiration of rat hepatocytes in vitro and in vivo. AB - Nitric oxide, a highly reactive radical, was recently identified as an intermediate of L-arginine metabolism in mammalian cells. We have shown that nitric oxide synthesis is induced in vitro in cultured hepatocytes by supernatants from activated Kupffer cells or in vivo by injecting rats with nonviable Corynebacterium parvum. In both cases, nitric oxide biosynthesis in hepatocytes was associated with suppression of total protein synthesis. This study attempts to determine the effect of nitric oxide biosynthesis on the activity of specific hepatocytic mitochondrial enzymes and to determine whether inhibition of protein synthesis is caused by suppression of energy metabolism. Exposure of hepatocytes to supernatants from activated Kupffer cells led to a 30% decrease of aconitase (Krebs cycle) and complex I (mitochondrial electron transport chain) activity. Using NG-monomethyl-L-arginine, an inhibitor of nitric oxide synthesis, we demonstrated that the inhibition of mitochondrial aconitase activity was due, in part, to the action of nitric oxide. In contrast, in vivo nitric oxide synthesis of hepatocytes from Corynebacterium parvum-treated animals had no effect on mitochondrial respiration. This suggests that inhibition of protein synthesis by nitric oxide is not likely to be mediated by inhibition of energy metabolism. PMID- 1899559 TI - Tumor necrosis factor alone does not explain the lethal effect of lipopolysaccharide. AB - Lethality and tumor necrosis factor production induced by different types of lipopolysaccharide were studied in naive (non-primed) rats during the late phase of endotoxin tolerance. The correlation with antilipopolysaccharide antibodies was also analyzed. No correlation was found between tumor necrosis factor levels and lipopolysaccharide-induced mortality in naive animals. Low-toxicity lipopolysaccharide preparations induced levels of tumor necrosis factor similar to those induced with more toxic types of lipopolysaccharide. Late tolerance was associated with progressively lower levels of lipopolysaccharide-induced tumor necrosis factor and increasing titers of antilipopolysaccharide antibodies after repeated injections of homologous lipopolysaccharide. During late endotonxin tolerance, a direct correlation between the lipopolysaccharide dose and peak tumor necrosis factor serum levels was found. We conclude that since tumor necrosis factor serum levels do not correlate with mortality, tumor necrosis factor alone cannot explain the lethal effect of lipopolysaccharide. PMID- 1899558 TI - Increased intestinal permeability in endotoxic pigs. Mesenteric hypoperfusion as an etiologic factor. AB - Infusing pigs with lipopolysaccharide (LPS) decreases superior mesenteric artery blood flow (Qsma), suggesting that mesenteric hypoperfusion may be responsible for LPS-induced alterations in gut mucosal permeability. To test this hypothesis, we studied four groups of anesthetized swine. Group 1 animals (N = 6) were infused with LPS (250 micrograms/kg over 1 hour beginning at 60 minutes) and continuously resuscitated with Ringer's lactate (48 mL/kg per hour). In group 2 (N = 5), Qsma was decreased by 50% by means of a mechanical occluder to mimic the LPS-induced alterations in Qsma observed in group I. Group 3 (N = 5) was included to document our ability to detect ischemia/reperfusion-induced alterations in mucosal permeability; in these pigs, Qsma was decreased in steps to zero flow (at 150 to 210 minutes) and then perfusion was restored (at 210 to 270 minutes). Pigs in group 4 (N = 6) served as normal controls; these animals were resuscitated with Ringer's lactate at the same rate as in group 1 but were not infused with LPS. To assess mucosal permeability, we measured plasma-to-lumen clearances for two markers, chromium 51-labeled edetic acid monohydrate (EDTA) and urea. Loading and maintenance infusions of the markers were given intravenously, and a 20-cm isolated segment of small intestine was continuously perfused at 2 mL/min with Ringer's lactate at 37 degrees C. Results were expressed as the ratio of the clearances for the two probes (CEDTA/CUREA). In group 3, CEDTA/CUREA was 999% +/- 355% of baseline at 270 minutes. In group 1, CEDTA/CUREA was 572% +/- 235% of baseline at 270 minutes. In groups 2 and 4, however, CEDTA/CUREA did not change significantly from the baseline value over the duration of the study. These data suggest that increased mucosal permeability after LPS is due to factors other than (or in addition to) mesenteric hypoperfusion. PMID- 1899560 TI - Relative contributions of host and microbial factors in bacterial translocation. AB - To study the relative contributions of host and microbial factors in bacterial translocation, germfree mice were mono-associated with either Proteus mirabilis, Escherichia coli, or Enterococcus faecalis. Germfree mice included T-cell deficient nude mice and normal littermates, natural killer cell-deficient beige mice and normal littermates, and triply immunodeficient mice with beige, T-cell, and B-cell mutations and their littermates. Each bacterial species colonized the cecum in similarly high numbers. Bacteria were recovered from the mesenteric lymph node of every mouse in inconsistent numbers, eg, greater numbers of P mirabilis and E coli were recovered from T-cell-deficient nude mice than from their normal littermates, but the opposite was observed with E faecalis. Comparing the three bacterial species resulted in relatively consistent observations, eg, the incidence of E faecalis translocation to the liver was greater than that of E coli or P mirabilis translocation. Thus, the identity of the translocating microbe significantly affected the recovery of viable translocating bacteria. PMID- 1899561 TI - Results of surgery for extratemporal partial epilepsy that began in childhood. AB - Thirty-five consecutive patients who underwent surgery for intractable extratemporal seizures originating in childhood are described. Candidates for surgery were selected on the basis of clinical criteria, neurodiagnostic imaging, and an electroencephalographic investigation that included the use of sphenoidal electrodes and long-term monitoring. Invasive preoperative monitoring was not used. Our results, with respect to the control of seizures and behavioral improvement, are comparable with series in which data from invasive recordings were used in the selection process. Sixty-three percent of the 35 patients (76.5% of those operated on after the introduction of long-term electroencephalographic monitoring) became either seizure free or experienced a reduction in their frequency of seizures by at least 75%. The favorable outcome in this group of patients strengthens the argument for early operation in children with intractable epilepsy, even when the seizure focus is outside the temporal lobe. PMID- 1899562 TI - Intraocular tissue plasminogen activator in a rabbit model of traumatic hyphema. AB - Tissue plasminogen activator was used to evaluate the clearance of traumatic hyphema in a rabbit model. A neodymium-YAG laser was used to disrupt iris vessels, creating a traumatic hyphema. Tissue plasminogen activator (1800 IU/0.1 mL) was injected into the anterior chamber 24 hours after creation of the hyphema. Two control groups (one receiving balanced salt solution and one receiving no treatment) were used for comparison. A multivariate analysis of covariance indicated that the greatest difference in hyphema clearance between the groups occurred at days 3, 4, and 5. Five days after tissue plasminogen activator treatment, the mean size of the clot remaining in the anterior chamber was 27% of that of the original hyphema. In control eyes, almost 60% of the original clot remained at day 5. Treatment of animals with tissue plasminogen activator doses of 5000 IU and 10,000 IU produced a substantial increase in repeated bleeding episodes in our rabbit model. We concluded that although the use of tissue plasminogen activator in our rabbit model of traumatic hyphema significantly improved clearance of blood from the anterior chamber, the remaining clot was of such size that the clinical benefit was questionable. PMID- 1899563 TI - Systemic mannitol increases retinal adhesiveness measured in vitro. AB - Pigmented rabbits were given mannitol intravenously, and at various times thereafter blood osmolality was measured and eyes were enucleated to measure retinal adhesiveness to the retinal pigment epithelium. Both blood osmolality and retinal adhesion increased in proportion to the dose of mannitol. We found a measurable increase in retinal adhesion as early as 10 minutes and as late as 4 hours after mannitol injection. We suspect that mannitol dehydrates the subretinal space and thereby enhances the adhesive properties of the interphotoreceptor matrix or tightens the interdigitation between photoreceptors and pigment epithelial cells. Our data suggest that mannitol could have clinical application in the management of retinal detachments. PMID- 1899564 TI - Substrate specificity of tissue-type and urokinase-type plasminogen activators. AB - Recent studies suggest that plasminogen activators not only hydrolyse a specific arginine-valine bond in plasminogen, but may also cleave other proteins such as fibronectin. We studied the substrate specificity, particularly the preference for arginyl over lysyl peptide bonds, of tissue-type plasminogen activator (t-PA) as well as of two-chain urokinase-type plasminogen activator (u-PA). The arginine/lysine preference was determined with three pairs of tripeptidyl-p nitroanilide substrates having either arginine or lysine in the P1 position and varied from 5.2 to 14.1 for u-PA and from 55.6 to 99.8 for t-PA. It was concluded that both t-PA and u-PA preferred arginyl to lysyl peptide bonds. However, u-PA had a significantly lower arginine/lysine preference than t-PA, indicating that u PA represents a less specific proteinase. This may point to functions of u-PA other than plasminogen activation, which involve cleavage of lysyl bonds. PMID- 1899565 TI - A 60-kDa phosphorylated protein from fetal human bone. AB - A phosphorylated protein was isolated and purified from fetal human bone. Fetal and adult human bones were decalcified with EDTA, and the extract from the fetal bone was fractionated using Q-Sepharose anion exchange chromatography. The fraction containing Ser(P) was purified by Sephacryl S-200 molecular sieving and C4 reverse-phase HPLC. The purified protein had a molecular weight of 60000 on SDS-PAGE, where the protein was stained with Rhodamine-B. The amino acid composition of this protein was different from any other reported phosphorylated proteins in human bone. However, this phosphorylated protein was difficult to detect in the adult bone extract on SDS-PAGE. PMID- 1899566 TI - Endothelin converting enzyme of bovine carotid artery smooth muscles. AB - This is the first report clearly demonstrating the presence of endothelin (ET) converting enzyme in vascular smooth muscle. Like cultured endothelial cells, noncultured vascular smooth muscle homogenate of bovine carotid arteries, converts human big ET- 1 to ET-1 at pH 3.0, pH 5.0 and pH 7.0, and the apparent ratio of these three activities is about 6:5:1, respectively. Peptides generated during incubation of the homogenate and big ET- 1 at the three pHs were identified as ET- 1 by radioimmunoassay and high performance liquid chromatography. The two acid enzymes are in the cytosol (103,000xg sup) and are inhibited by pepstatin A, while the neutral enzyme is sensitive to EDTA or phosphoramidon; 73% of the neutral enzyme activity was membrane-bound and the remainder (27%) cytosolic. PMID- 1899567 TI - Ca2(+)-dependent amylase secretion from pancreatic acinar cells occurs without activation of phospholipase C linked G-proteins. AB - We have examined the influence of guanine nucleotides on Ca2(+)-dependent amylase secretion from SLO permeabilized rat pancreatic acini. GTP gamma S (100 microM) stimulated Ca2+ dependent amylase release, decreasing the EC50 for Ca2+ from 1.4 to 0.8 microM. By contrast, GDP (1mM) and dGDP (1mM) inhibited the maximal Ca2(+) dependent secretory response. Measurement of IP3 liberation showed that Ca2+ stimulation did not increase the activity of phospholipase C (PLC) postulated to be linked to a G-protein termed Gp; GDP and dGDP must therefore be exerting their inhibitory action via a GTP-binding protein distinct from the PLC-linked Gp. PMID- 1899568 TI - Tissue and subcellular distributions of an inhibitory GDP/GTP exchange protein (GDI) for smg p25A by use of its antibody. AB - We have recently purified from bovine brain cytosol to near homogeneity a GDP/GTP exchange protein for smg p25A, named smg p25A GDI, that inhibits the dissociation of GDP from and the subsequent binding of GTP to smg p25A. In the present study, we made an antiserum against smg p25A GDI and studied its tissue distribution in rat and its subcellular distribution in rat cerebrum by use of this antiserum. smg p25A GDI was found in secretory cells with both regulated and constitutive secretion types. Since smg p25A was previously found in only secretory cells with a regulated secretion type, this result suggests that small GTP-binding proteins different from smg p25A but recognized by smg p25A GDI are present in secretory cells with a constitutive secretion type, and that smg p25A GDI is involved in both regulated and constitutive secretory processes. In subcellular fractionation analysis of rat cerebrum, smg p25A GDI was mostly found in the cytosol fraction of neuron body and synaptosome. In synaptosome, it was mainly found in the synaptic cytosol. PMID- 1899569 TI - Isolation of human brain protein kinase C: evidence for kinase C catalytic fragment modulating G protein-GTPase activity. AB - Protein kinase C from human brain was isolated and characterized. A protein kinase M like kinase of molecular weight 63 kDa was also partially purified and identified by its immunological properties similar to those of kinase C. The kinase M like kinase activity, devoid of Ca2+ and phospholipids dependency, was also characterized by its inhibition profile by several ligands. Since this kinase phosphorylates a G protein (M.W. 36 kDa) and decreases its GTPase activity which could be restored by alkaline phosphatase, it is concluded that this kinase M like kinase could interact with G protein mediated events of neuronal responses. PMID- 1899570 TI - Low molecular weight GTP-binding proteins associated with zymogen granule membranes from rat pancreas. AB - We report here that at least seven low Mr GTP-binding proteins (range 21.5 to 29 kDa) are associated with the membranes of zymogen granules from rat pancreas. GTP binding proteins of similar Mr but in different relative proportions were found in the cytosolic fraction. Treatment of intact granules with either trypsin or proteinase K caused the complete digestion of all the GTP-binding proteins, indicating that the proteins are located on the cytoplasmic face of the granule membrane. All the GTP-binding proteins were relatively resistant to extraction by 1.0M NaCl, 6.0M urea and 0.2M Na2CO3 (pH 11.0) but partitioned into the detergent phase of Triton X 114 extracts indicating that the proteins are tightly associated with the granule membrane. By analogy with the function of other small Mr GTP-binding proteins in regulation of membrane fusion events in eukaryotic cells, we suggest that these low Mr GTP-binding proteins in the pancreatic acinar cell may be involved in regulated secretion. PMID- 1899572 TI - Identification of the NADH-binding subunit of energy-transducing NADH-quinone oxidoreductase (NDH-1) of thermus thermophilus HB-8. AB - The energy-transducing NADH--quinone oxidoreductase (NDH-1) isolated from Thermus thermophilus HB-8 is composed of approximately 10 unlike polypeptides and contains noncovalently bound FMN and at least three iron-sulfur clusters [Yagi, T., Hon-nami, K., and Ohnishi, T. (1988) Biochemistry 27, 2008-2013]. When NDH-1 of T. thermophilus HB-8 was irradiated by short UV light in the presence of [adenylate-32P]NADH or [adenylate-32P]NAD, radioactivity was incorporated into a single polypeptide of Mr 47,000. The labeling of the Mr 47,000 polypeptide was diminished when UV irradiation of the enzyme complex with [adenylate-32P]NAD was carried out in the presence of NADH or deamino-NADH which act as substrates for the NDH-1, but not in the presence of NADP(H) or AMP which act neither as substrates nor as competitive inhibitors. These results strongly suggest that the Mr 47,000 polypeptide is an NADH-binding subunit of the NDH-1 of T. thermophilus HB-8. PMID- 1899571 TI - A pH-dependent phospholipase A2 contributes to loss of plasma membrane integrity during chemical hypoxia in rat hepatocytes. AB - Previous studies have suggested that alterations in phospholipid composition of plasma membranes may underlie lethal cell injury due to hypoxic and ischemic injury. The present study was designed to determine if such alterations are due to the activation of a pH-dependent phospholipase A2. Loss of cell viability and phospholipase A2 activity measured by arachidonic acid release increased in parallel during metabolic inhibition with KCN and iodoacetate (chemical hypoxia). Acidosis (pH 6.5) and the phospholipase inhibitors, dibucaine and mepacrine, delayed loss of cell viability and release of arachidonic acid to a similar extent. These findings suggest that a pH-dependent phospholipase A2 causes alterations in plasma membrane phospholipid composition after ATP-depletion which contribute to lethal cell injury. PMID- 1899573 TI - Lipoxygenation in rat brain? AB - It has been previously claimed that rodent brain possesses lipoxygenase activity, based upon the structure of products which were formed from arachidonic acid and the inhibition of this activity by "lipoxygenase inhibitors." Our studies confirm that various positional isomers of hydroxyeicosatetraenoic acids (HETE) are formed (e.g., 15-, 12-, 11-, 9-, 8- and 5-HETE) by brain homogenate and that their production is inhibited by certain lipoxygenase inhibitors, such as nordihydroguaiaretic acid (NDGA) but not by cyclooxygenase or cytochrome P-450 inhibitors. However, stereochemical analysis indicated racemic distributions of these products suggesting that they were not formed by a lipoxygenase enzyme but rather by a peroxidative process. It should also be noted that the presence of 12(S)-lipoxygenase activity could be demonstrated by stereochemical analysis only when the brain was not perfused properly, indicating this activity was due to blood cell contamination. It is known that many lipoxygenase inhibitors are also capable of inhibiting peroxidative reactions apparently due to their free radical scavenging properties. For these reasons, it is essential that the stereochemical purity of purported lipoxygenase products be determined and that previous claims of lipoxygenase activity in mammalian brain be reexamined. PMID- 1899574 TI - Mitochondrial DNA mutations in mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). AB - The total sequences of mitochondrial DNA were determined in two patients with juvenile-onset mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) due to Complex I deficiency. Patients 1 and 2 had three and two unique point mutations, respectively, causing replacement of phylogenically conserved amino acids. A transition from G to A was found at nucleotide position 5601 in the alanine tRNA gene of Patient 2, and a transition from A to G was found at 3243 in the leucine (UUR) tRNA gene of both patients. The latter mutation located at the phylogenically conserved 5' end of the dihydrouridine loop of the tRNA molecule, and was present in two patients with adult-onset MELAS and absent in controls. These results indicate that a mass of mtDNA mutations including the A-to-G transition in the tRNA(Leu) gene is a genetic cause of MELAS. PMID- 1899575 TI - Activation by cromakalim of pre- and post-synaptic ATP-sensitive K+ channels in substantia nigra. AB - Membrane potentials and synaptic potentials were recorded using the patch clamp technique from neurons isolated from the substantia nigra. Intracellular perfusion of dopaminergic neurons with an ATP-free solution caused hyperpolarization and inhibition of firing. Intracellular perfusion with a solution containing 2 mM ATP prevented this hyperpolarization, but application of the K+ channel openers cromakalim and pinacidil caused a similar hyperpolarization as well as the disappearance of bicuculline-sensitive synaptic potentials. All these effects were reversed by sulfonylureas, indicating that they are mediated by ATP-sensitive K+ channels. It is concluded that K+ channel openers activate ATP-sensitive K+ channels both presynaptically on GABAergic terminals and postsynaptically on substantia nigra dopaminergic neurons. PMID- 1899576 TI - Transcription of fra-2 mRNA and phosphorylation of Fra-2 protein are stimulated by serum. AB - The RNA transcript and the gene product of a newly isolated fos-related gene, fra 2, were analyzed in growth-arrested and growth-stimulated chicken embryo fibroblasts (CEF). In the growth-arrested cells, a small amount of 6.8 kilobase (kb) fra-2 transcript was synthesized and several species (40-46 kilodaltons (kd) of hypophosphorylated fra-2 gene products (Fra-2) were detected. After the growth stimulation, two species of fra-2 transcripts of 6.8 kb and 5.7 kb were transiently induced. Compared with c-fos mRNA, expression of these fra-2 mRNAs was significantly prolonged, in good agreement with the previous analysis on the synthetic rate of Fos and Fra-2 proteins. Upon growth stimulation, Fra-2 undergoes more extensive phosphorylation on serine residues to form a 46 kd band, possibly owing to the protein kinase activity induced by serum. PMID- 1899579 TI - Sex determination and the generation of sexually dimorphic nervous systems. PMID- 1899578 TI - Inhibition of human monocyte chemotaxis and chemiluminescence by Pseudomonas aeruginosa elastase. AB - The in vitro effect of Pseudomonas aeruginosa elastase on human monocyte function was examined. Mononuclear cells isolated from the peripheral blood of healthy individuals were incubated with various concentrations of elastase, and the chemotactic activity and chemiluminescence response of these cells were measured after washing the cells free of the enzyme. Elastase at concentrations of 0.1 micrograms/ml and higher inhibited the chemotactic activity of monocytes towards F-Met-Leu-Phe and zymosan-activated serum. The inhibition of chemiluminescence response was observed at as low as 0.125 micrograms/ml elastase. Monocytes/macrophages are known to be involved in the inflammation observed in the lungs of patients infected by P. aeruginosa. The inhibition of monocyte function by elastase may serve as an escape mechanism for this bacterium from these cells. PMID- 1899577 TI - Expression of human Alzheimer amyloid precursor protein in insect cells. AB - The amyloid beta-peptide is a major constituent of amyloid deposited in the brains of patients with Alzheimer's disease and is derived from a larger precursor protein/s (APP-695, 751, 770). A human cDNA encoding full-length APP 751 was inserted into the genome of Autographa californica nuclear polyhedrosis virus under transcriptional regulation of the viral polyhedrin gene promoter. The recombinant virus was used to infect insect cells, which resulted in the abundant expression of APP-751. Analysis of infected cell proteins indicate that APP-751 is localized in the membrane fraction; however, a significant amount of the protein was cleaved and released into the medium. The NH2-terminal sequence of recombinant APP-751 from the membrane fraction was identical to that of mammalian APP. Immunoblot analysis suggests that the secreted form results from cleavage within the beta-peptide. PMID- 1899580 TI - Unusual topography of bovine rhodopsin promoter-lacZ fusion gene expression in transgenic mouse retinas. AB - To define the cis-acting DNA elements required for rhodopsin expression, we generated lines of transgenic mice carrying sequences upstream of the bovine rhodopsin gene fused to the E. coli beta-galactosidase gene (lacZ). Upstream sequences extending from -2174 to +70 bp, from -734 to +70 bp, and from -222 to +70 bp direct photoreceptor-specific expression. All three -2174 lines demonstrate a superior-temporal to inferior-nasal gradient of expression across the retina, whereas lines carrying the shorter constructs demonstrate either spatially continuous expression across the retina, discrete clusters of expression, or both. As a complementary approach to defining regulatory elements, we compared DNA sequences 5' of the murine, bovine, and human rhodopsin genes. Significant homology between all three species was found just upstream of the transcription start site and at approximately 1.5 kb upstream. PMID- 1899581 TI - Modulation of a cloned mouse brain potassium channel. AB - The mouse brain K+ channel (MBK), previously cloned by others, has been independently cloned and shown to express in Xenopus oocytes. This K+ current (IK) inactivated over a time course of seconds and was sensitive to the K+ channel-blocking reagent tetraethylammonium. When the K+ channel was coexpressed with a cloned mouse brain serotonin receptor (5HT1c) in oocytes, activation of the 5HT1c receptor by a brief application of serotonin resulted in a suppression of the IK amplitude over the next 20 min. IK could also be suppressed by activation of G proteins. Suppression was also caused by intracellular Ca2+ injections and was blocked by intracellular injection of EGTA. Calmodulin antagonists block the IK suppression, but a known protein kinase inhibitor did not block suppression. The 5HT1c suppression was reversible; recovery from suppression was blocked by the protein kinase inhibitor H-7. These data suggest that the IK suppression occurs through a novel mechanism independent of A- or C type protein kinases; suppression is best explained as being due to the action of a Ca2+/calmodulin-activated phosphatase; recovery from suppression is due to the action of a protein kinase. PMID- 1899582 TI - Ventricular arrhythmias during treatment with alteplase (recombinant tissue plasminogen activator) in suspected acute myocardial infarction. AB - Continuous electrocardiography during the first 24 hours of a stay in a coronary care unit was used to record ventricular arrhythmias during treatment with alteplase (recombinant tissue plasminogen activator) or placebo. Recordings were made on 378 of the 436 patients admitted to a double blind trial of alteplase or placebo in one participating centre of the Anglo-Scandinavian study of early thrombosis (ASSET), patients being selected according to the availability of recorders. Of these, 309 (158 given alteplase and 151 placebo) had greater than 5 hours of analysable data. Most of the arrhythmias were recorded in patients with an in hospital diagnosis of myocardial infarction. Ventricular couplets and ventricular tachycardia were significantly more common in the patients treated with alteplase. Further, in patients with myocardial infarction who had ventricular extrasystoles, couplets, or ventricular tachycardia type a, the number of hours in which each arrhythmia was recorded was significantly higher in the alteplase group. The various ventricular arrhythmias in the alteplase group tended to cluster in the first 4-12 hours of the recordings. During the first 24 hours admission there were four episodes of ventricular fibrillation in the alteplase group and five in the placebo group of taped patients. By one month there had been 18 deaths in these 309 patients (alteplase four, placebo 14). These bore no relation to any recorded arrhythmia. Clinical records for the patients with no or minimal tape data yielded six further episodes of ventricular fibrillation during the first 24 hours (three in the alteplase group and three in the placebo group). Of the total 436 patients, 10 of the 218 patients in the alteplase group had died by one month compared with 22 of the 218 patients treated with placebo. The use of alteplase increases the incident of non-life threatening ventricular arrhythmias. These results, however suggest that arrhythmia after thrombolysis in the pre-hospital phase may be less of a problem than it is perceived to be. PMID- 1899584 TI - Left anterior fascicular block: an ischaemic response during treadmill testing. AB - A patient in whom exercise induced reversible ischaemic left anterior fascicular block is reported. Glyceryl trinitrate relieved the fascicular block. Coronary angiography showed a 90% obstruction of the left anterior descending artery. The left anterior fascicular block induced by exercise disappeared after a successful coronary angioplasty. PMID- 1899583 TI - Flecainide in the treatment of fetal tachycardias. AB - Fourteen mothers were treated with flecainide for fetal atrial tachycardias associated with intrauterine cardiac failure. Twelve of the 14 fetuses responded by conversion to sinus rhythm. One of the 12 fetuses subsequently died in utero. The remaining fetuses suffered no morbidity and were alive and well 3 months to 2 years after delivery. The two fetuses in whom atrial tachycardia did not convert with flecainide were successfully treated with digoxin. These results compare favourably with previous forms of antiarrhythmic treatment. After recent reports of the side effects of flecainide treatment, however, it has been advised that this drug should be confined to high risk patients and those with life threatening arrhythmias. The use of flecainide for fetal arrhythmias should be limited to patients with severe fetal hydrops and supraventricular tachycardias. It should not be the first drug of choice in atrial flutter. PMID- 1899585 TI - Amiodarone, nifedipine, sodium cromoglycate. PMID- 1899586 TI - Gulf War casualties. Clinical guidance for nurses. PMID- 1899587 TI - Images of India: open sewers and incense. PMID- 1899588 TI - Biofilms and urethral catheter infections. PMID- 1899589 TI - Nurse prescribing: wound management in the community. PMID- 1899590 TI - Open learning: opportunities for enrolled nurses. PMID- 1899592 TI - Education: mixing and matching. PMID- 1899591 TI - Quality assurance: multidisciplinary clinical audit. PMID- 1899593 TI - Working mothers: shiftless mothers? PMID- 1899594 TI - Cardiology update. The coronary care unit. PMID- 1899595 TI - Cardiology update. Mitral valvuloplasty: the Inoue technique. PMID- 1899596 TI - Cardiology update. Social class and CHD. PMID- 1899597 TI - Cardiology update. Electrophysiology and ablation studies. PMID- 1899598 TI - Professional conduct. Exerting undue influence. PMID- 1899599 TI - Nurses' pay. Staging the award. PMID- 1899600 TI - Asthma on the line. PMID- 1899601 TI - Attitudes to clients with mental handicap. AB - The increase in community care provision for people with a mental handicap makes an understanding of the attitudes and motivations of staff caring for them an urgent priority. Norma Raynes and colleagues describe a Department of Health sponsored study which investigated the quality of care delivered in four key sectors of community residential care. Their findings reveal the positive attitudes of staff in all four settings and suggest that local authorities have a potential source of highly motivated recruits among those working in the health, voluntary and private sectors. PMID- 1899602 TI - Responding to resource management. AB - The pressures for change within the National Health Service will force managers and practitioners to work together to ensure planned and effective implementation of reforms. Using a case study as illustration, Philip Munson demonstrates the problems nurses can experience when the execution of change projects is mismanaged. PMID- 1899603 TI - The real value of people. PMID- 1899604 TI - The nurse as a consultant. AB - The use of the term 'consultant' by a nurse may be seen by some as an attempt to encroach into territory which is the rightful preserve of the medical profession but, claim the authors of this article, such thinking is unjustified and reactionary. The various roles of the nurse consultant, and the benefits which can accrue from them, are outlined. Paramount in any consideration of the appropriate status of the consultant role is the need to keep it clinically based. PMID- 1899605 TI - Training for health care assistants. AB - The adequate preparation of health care assistants is a matter which is causing nurses great concern. Neil Headford outlines the initiative developed by Barnsley Health Authority which is designed to comply with the recommendations of statutory educational bodies. The meticulously designed course offers health care assistants broad and challenging opportunities and is based on the principles of adult and open learning. Assessment of performance is achieved through a competency model which draws on the ideas of established researchers. PMID- 1899606 TI - 'The age of unreason' and the charge nurse. AB - In this introduction to a major six-part series on issues in ward management facing charge nurses, series co-ordinator Ros Brown urges a positive attitude towards the momentous changes which are taking place in the National Health Service in general and nursing in particular. It is important, she argues, that charge nurses consider the potential opportunities which might arise from change and reform; otherwise, 'a wave of disinvestment' in the service might be created at a time when commitment and endeavour are perhaps needed most. Ros Brown's incisive analysis sets the scene for the issues which will be explored in subsequent articles. The first part of the series appears in next week's edition of Nursing Standard. PMID- 1899607 TI - Points of view. Helping enrolled nurses develop their careers. PMID- 1899609 TI - Speak your mind. PMID- 1899608 TI - Watch your language. PMID- 1899610 TI - A force for change. Interview by John Naish. PMID- 1899611 TI - Give us credit. PMID- 1899612 TI - Smile please. PMID- 1899613 TI - Career change. In and out of nursing. PMID- 1899614 TI - Spirituality. The inner light. PMID- 1899615 TI - I nurse therefore.... PMID- 1899616 TI - Conference capers. PMID- 1899617 TI - Indomethacin inhibits the chemical carcinogen benzo(a)pyrene but not dimethylbenz(a)anthracene from altering Langerhans cell distribution and morphology. AB - Treatment of murine skin with the polyaromatic hydrocarbon carcinogens benzo(a)pyrene (BP) or dimethylbenz(a)anthracene (DMBA) for 3 weeks resulted in an increase and a decrease in epidermal Langerhans cell (LC) numbers, respectively, compared with solvent-treated skin. Implantation of subcutaneous indomethacin pellets prior to carcinogen treatment prevented the changes in LC numbers and morphology in BP, but not DMBA-treated skin. Indomethacin treatment was also found to reduce elevated prostaglandin E2 (PGE)2 levels in the skin of BP-treated mice, whereas PGE2 levels were not significantly raised in DMBA treated mice. There thus appears to be a link between altered prostaglandin levels and LC numbers in murine skin treated with BP, but not DMBA. In the latter, LC numbers were reduced by mechanisms not reversed by indomethacin. It is concluded that increased prostaglandin levels may contribute to the impairment of cutaneous immunity previously observed in BP-treated mice by altering LC density and morphology within the epidermis. PMID- 1899618 TI - Enhancement of the catalytic properties of human carbonic anhydrase III by site directed mutagenesis. AB - Among the seven known isozymes of carbonic anhydrase in higher vertebrates, isozyme III is the least efficient in catalytic hydration of CO2 and the least susceptible to inhibition by sulfonamides. We have investigated the role of two basic residues near the active site of human carbonic anhydrase III (HCA III), lysine 64 and arginine 67, to determine whether they can account for some of the unique properties of this isozyme. Site-directed mutagenesis was used to replace these residues with histidine 64 and asparagine 67, the amino acids present at the corresponding positions of HCA II, the most efficient of the carbonic anhydrase isozymes. Catalysis by wild-type HCA III and mutants was determined from the initial velocity of hydration of CO2 at steady state by stopped-flow spectrophotometry and from the exchange of 18O between CO2 and water at chemical equilibrium by mass spectrometry. We have shown that histidine 64 functions as a proton shuttle in carbonic anhydrase by substituting histidine for lysine 64 in HCA III. The enhanced CO2 hydration activity and pH profile of the resulting mutant support this role for histidine 64 in the catalytic mechanism and suggest an approach that may be useful in investigating the mechanistic roles of active site residues in other isozyme groups. Replacing arginine 67 in HCA III by asparagine enhanced catalysis of CO2 hydration 3-fold compared with that of wild type HCA III, and the pH profile of the resulting mutant was consistent with a proton transfer role for lysine 64. Neither replacement enhanced the weak inhibition of HCA III by acetazolamide or the catalytic hydrolysis of 4 nitrophenyl acetate. PMID- 1899619 TI - Heterogeneity in the tyrosine sulfation of Chinese hamster ovary cell produced recombinant FVIII. AB - By the use of recombinant technology, several stable Chinese hamster ovary (CHO) cell lines expressing human FVIII were established. Thrombin treatment and SDS PAGE analysis of the purified recombinant FVIII (rFVIII) revealed a striking difference from plasma-derived FVIII (pFVIII). A 43-kDa fragment of the FVIII heavy chain appears as a double band from rFVIII, while a single band from pFVIII is observed. All other fragments from the two samples appeared similar by SDS PAGE. The heterogeneity is caused by incomplete tyrosine sulfation of one or more of the three potential tyrosine sulfation sites (Tyr718, Tyr719, Tyr723). To investigate if there is a general limitation and heterogeneity in the tyrosine sulfation of rFVIII, two other potential tyrosine sulfation sites on the FVIII light chain (Tyr1664, Tyr1680) were analyzed. The results show that both sites on the pFVIII light chain and on the rFVIII light chain are completely sulfated. The limitation of CHO cells to tyrosine sulfate rFVIII is therefore only restricted to a few sites. The two sulfated forms of rFVIII can easily be separated by ion exchange chromatography, indicating the importance of the sulfate groups on the charge and/or conformation of FVIII. Both forms of rFVIII possess identical in vitro coagulation activity, von Willebrand factor binding, and thrombin activation profile. However, the difference in tyrosine sulfation may change other biological properties of FVIII. PMID- 1899620 TI - Details of mannitol transport in Escherichia coli elucidated by site-specific mutagenesis and complementation of phosphorylation site mutants of the phosphoenolpyruvate-dependent mannitol-specific phosphotransferase system. AB - The mannitol transport protein (EIImtl) carries out translocation with concomitant phosphorylation of mannitol from the periplasm to the cytoplasm, at the expense of phosphoenolpyruvate (PEP). The phosphoryl group which is needed for this group translocation is sequentially transferred from PEP via two phosphorylation sites, located exclusively on the C-terminal cytoplasmic domain, to mannitol. Oligonucleotide-directed mutagenesis was used to investigate the precise role of these sites in phosphoryl group transfer, by producing specific amino acid substitutions. The first phosphorylation site, His-554 (P1), was replaced by Ala, which renders the EII-H554A completely inactive in PEP-dependent mannitol phosphorylation, but not in mannitol/mannitol 1-phosphate exchange. The P2 site mutant, EII-C384S, was inactive both in the mannitol phosphorylation reaction and in the exchange reaction, due to replacement of the essential Cys 384 by Ser. Although EII-H554A and EII-C384S were both catalytically inactive in the PEP-dependent phosphorylation, EII-C384S was able to restore up to 55% of the wild-type mannitol phosphorylation activity with the EII-H554A mutant, indicating a direct phosphotransfer between two subunits. These phosphorylation data together with the data obtained from mannitol/mannitol phosphate exchange kinetics, after mixing EII-H554A and EII-C384S, indicated the formation of functionally stable heterodimers, which consist of an EII-H554A and an EII-C384S monomer. PMID- 1899621 TI - The 30-kilodalton subunit of bovine mitochondrial complex I is homologous to a protein coded in chloroplast DNA. AB - In cattle, 7 of the 30 or more subunits of the respiratory enzyme NADH:ubiquinone reductase (complex I) are encoded in mitochondrial DNA, and potential genes (open reading frames, orfs) for related proteins are found in the chloroplast genomes of Marchantia polymorpha and Nicotiana tabacum. Homologues of the nuclear-coded 49- and 23-kDa subunits are also coded in chloroplast DNA, and these orfs are clustered with four of the homologues of the mammalian mitochondrial genes. These findings have been taken to indicate that chloroplasts contain a relative of complex I. The present work provides further support. The 30-kDa subunit of the bovine enzyme is a component of the iron-sulfur protein fraction. Partial protein sequences have been determined, and synthetic oligonucleotide mixtures based on them have been employed as hybridization probes to identify cognate cDNA clones from a bovine library. Their sequences encode the mitochondrial import precursor of the 30-kDa subunit. The mature protein of 228 amino acids contains a segment of 57 amino acids which is closely related to parts of proteins encoded in orfs 169 and 158 in the chloroplast genomes of M. polymorpha and N. tabacum. Moreover, the chloroplast orfs are found near homologues of the mammalian mitochondrial genes for subunit ND3. Therefore, the plant chloroplast genomes have at least two separate clusters of potential genes encoding homologues of subunits of mitochondrial complex I. The bovine 30-kDa subunit has no extensive sequences of hydrophobic amino acids that could be folded into membrane-spanning alpha helices, and although it contains two cysteine residues, there is no clear evidence in the sequence that it is an iron-sulfur protein. PMID- 1899622 TI - Effects of cytochalasin, phalloidin, and pH on the elongation of actin filaments. AB - We used electron microscopy to measure the effects of cytochalasins, phalloidin, and pH on the rates of elongation at the barbed and pointed ends of actin filaments. In the case of the cytochalasins, we compared the effects on ATP- and ADP-actin monomers. Micromolar concentrations of either cytochalasin B (CB) or cytochalasin D (CD) inhibit elongation at both ends of the filament, about 95% at the barbed end and 50% at the pointed end, so that the two ends contribute about equally to the rate of growth. Half-maximal inhibition of elongation at the barbed end is at 0.1 microM CB and 0.02 microM CD for ATP-actin and at 0.1 microM CD for ADP-actin. At the pointed end, CD inhibits elongation by ATP-actin and ADP actin about equally. At high (2 microM) concentrations, the cytochalasins reduce the association and dissociation rate constants in parallel for both ADP- and ATP actin, so their effects on the critical concentrations are minimal. These observations confirm and extend those of Bonder and Mooseker [Bonder, E. M., & Mooseker, M. S. (1986) J. Cell Biol. 102, 282-288]. The dependence of the elongation rate on the concentration of both cytochalasin and actin can be explained quantitatively by a mechanism that includes the effects of cytochalasin binding to actin monomers [Godette, D. W., & Frieden, C. (1986) J. Biol. Chem. 261, 5974-5980] and a partial cap of the barbed end of the filament by the complex of ADP-actin and cytochalasin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1899623 TI - Activation of human monocytes by granulocyte-macrophage colony-stimulating factor: increased urokinase-type plasminogen activator activity. AB - Granulocyte-macrophage colony-stimulating factor (GM-CSF) raised the plasminogen activator (PA) activity of cultured human monocytes. This activity was characterized to be urokinase-PA (u-PA) by incubation with specific IgG and by sodium dodecyl sulfate-polyacrylamide gel electrophoresis zymography. Increased u PA activity reflected GM-CSF-induction of u-PA mRNA levels. The stimulatory properties of GM-CSF for monocyte PA activity differed from those of interleukin 4, which induced monocyte tissue-type PA (t-PA) activity, and of interferon-gamma (IFN-gamma), which alone was not stimulatory but augmented lipopolysaccharide induced t-PA activity. GM-CSF alone did not stimulate detectable monocyte t-PA activity but combined with IFN-gamma to promote this activity. Plasmin formation arising from GM-CSF-induced u-PA in monocytes may contribute to the matrix turnover involved in, eg, cell migration and inflammation, and may explain some of the pathology seen in GM-CSF transgenic mice. PMID- 1899624 TI - Treatment of pure red cell aplasia after major ABO-incompatible bone marrow transplantation with recombinant erythropoietin. PMID- 1899626 TI - Pharmacological effects of a new antiarthritic agent, IX 207-887. PMID- 1899625 TI - Immune modifying effects of misoprostol and natural prostaglandins. AB - The synthetic prostaglandin misoprostol was found to enhance the immunosuppressive effects of cyclosporine A in vitro on human peripheral lymphocytes and mouse spleen cells, by synergizing with the latter drug, although on its own misoprostol was not potent as an immunosuppressive. These results suggest the possibility of exploiting the use of synthetic prostaglandins as adjunctive therapy in preventing clinical transplant rejection. PMID- 1899627 TI - Mobile extracorporeal shockwave lithotripsy. AB - During the last 18 months, extracorporeal shockwave lithotripsy (ESWL) has been provided at Epsom District Hospital using a mobile unit containing a Dornier HM4 lithotriptor. Patients with upper ureteric and renal stones were selected for treatment, which was performed without anaesthesia or sedation as a day-case procedure; 83 patients were treated, 5 of them with bilateral stones. Seventy patients required 1 treatment session, 17 required 2 and 1 patient required 3. There were no serious complications but 3 patients needed ureteroscopy to remove obstructing stones. The overall success rate was 86%. The cost to treat each NHS patient was 253 pounds. Mobile lithotripsy as a day-case procedure is a safe and cost-effective means of treating urolithiasis and can be performed in a District General Hospital. PMID- 1899628 TI - Analysis of the spontaneous in vitro anti-HIV-1 antibody secretion by peripheral blood mononuclear cells in HIV-1 infection. AB - We studied the spontaneous in vitro secretion of anti-HIV-1 antibodies by peripheral blood mononuclear cells (PBMC) from HIV-1-infected patients. Specific antibody production was detected in supernatants of PBMC cultures using an ELISA; HIV-1 specificity was confirmed by antigen adsorption and Western blotting. This antibody secretion was found to be an active phenomenon and was not due to a release of plasma antibodies passively adsorbed onto the cell membranes. In all positive supernatants, anti-HIV-1-secreted antibodies were directed against env encoded antigens and many supernatants also contained antibodies to pol- and gag encoded antigens. PBMC from all HIV-1-infected patients tested (140 adults and 18 infants) secreted anti-HIV-1 antibodies. This production was found during all the clinical stages of HIV-1 infection. Our results suggest that this spontaneous HIV 1-specific antibody secretion represents a marker of HIV-1 infection. Detection of these antibodies could be a valuable tool for early confirmation of HIV-1 infection in neonates born to HIV-1-seropositive mothers. PMID- 1899629 TI - Both IgA subclasses are reduced in parotid saliva from patients with AIDS. AB - Secretory IgA (SIgA), the isotypes IgA1 and IgA2, and IgM were measured by ELISA in stimulated parotid saliva from patients with AIDS (n = 16), subjects with asymptomatic HIV infection (n = 28), and HIV-seronegative healthy controls (n = 19). SIgA was significantly reduced in the AIDS group (10.4 micrograms/ml) compared with the asymptomatic HIV-infected subjects (17.1 micrograms/ml) and the controls (23.0 micrograms/ml). This decrease comprised both IgA1 and IgA2 to a similar extent on a relative basis. The SIgA decrease in AIDS patients was in striking contrast to their serum IgA level, which was significantly increased (6.9 g/l) compared with the asymptomatic HIV-infected subjects (2.9 g/l) as well as the controls (2.8 g/l). Low parotid output of SIgA in patients with HIV infection was associated with low numbers of CD4+ lymphocytes in peripheral blood as well as the presence of oral infections. The parotid output of IgM was similar in all groups. A low level of SIgA in the external secretions of patients with AIDS may well contribute to their frequent mucosal infections of opportunistic microorganisms. PMID- 1899630 TI - Individual germinal centres of myasthenia gravis human thymuses contain polyclonal activated B cells that express all the Vh and Vk families. AB - Using in situ hybridization, we analysed the immunoglobulin repertoire expressed by the B cells present in myasthenia gravis thymuses from four patients. B cells, mostly in activated state, were clustered in germinal centres, in which multiple isotypes were identified. A majority of cells expressed IgG as compared with IgM, with a roughly similar contribution of kappa and lambda chains. Hybridization with the six VH and the 4 VK human family probes was observed in serial sections, providing additional evidence that individual germinal centres were polyclonal. The thymic B cell repertoire closely reflected the VH and the VK family usage of normal peripheral blood lymphocytes with the preferential utilization of VH3, VK1 and VK3. PMID- 1899631 TI - Expression of rheumatoid factor associated cross-reactive idiotopes by glandular B cells in Sjogren's syndrome. AB - B cell expression of the germline gene-encoded, kappa IIIb-associated, rheumatoid factor (RF) cross-reactive idiotope (CRI) 17-109 and three VHI associated RF CRIs (G6, G8, H1) was investigated immunocytochemically in labial salivary glands from nine patients with primary and six with secondary Sjogren's syndrome, and in inflamed submandibular salivary glands from 10 patients with no history of connective tissue disease. Expression of CRIs by B cell infiltrates in labial glands from patients with primary and secondary Sjogren's syndrome were similar. Lymphoid infiltrates of labial glands from Sjogren's syndrome patients contained a higher proportion of kappa III+ cells reactive for the kappa IIIb-associated 17 109 idiotope (P less than 0.01) and larger G6 (P less than 0.02) and H1 (P less than 0.01) positive B cell populations than those within inflamed submandibular salivary glands. Furthermore, in labial glands there was a significant correlation between numbers of 17-109 and G6 idiotope reactive cells (r = 0.61; P less than 0.02), reflecting the known association between these H and L chain CRIs in RF IgM paraproteins. These results indicate that B cells bearing both VKIII and VHI-associated CRI are increased in the glandular infiltrates in Sjogren's syndrome and support the idea that this condition is associated with proliferation of immature B cell clones retaining germ-line V genes. PMID- 1899632 TI - Low CD4/CD8 T lymphocyte ratio in acute myocardial infarction. AB - T lymphocyte subsets were analysed using monoclonal antibodies and flow cytometry to determine whether myocardial infarction and cardiopulmonary resuscitation induce changes in these. Groups of 11 infarct patients and 10 patients with past cardiopulmonary resuscitation were compared with 11 age- and sex-matched controls and 12 sepsis patients. The differences in the CD4/CD8 ratios between the four groups were significant (F = 7.71, P = 0.001). The infarct patients had lower CD4/CD8 ratios (mean +/- s.d. 0.83 +/- 0.43) than the control (2.12 +/- 1.13; P = 0.001) or sepsis cases (1.76 +/- 1.05; P = 0.004), but their ratios did not differ from those of the resuscitation group (0.93 +/- 0.79, P = 0.84). The latter group also had lower ratios than the control (P = 0.003) and sepsis groups (P = 0.013). Most infarct patients had an on admission inverted CD4/CD8 ratio which usually returned to normal in the next 2 days. A permanently low CD4/CD8 ratio may be a poor sign prognostically after both myocardial infarction and resuscitation. PMID- 1899633 TI - Experimental induction of heterotopic bone. AB - Heterotopic bone can be induced in experimental animals by trauma to the soft tissues, by induction from living cells, or by extracts from bone and teeth. In the first two types, the mechanism of the inductive process is not known, whereas in the latter, a factor isolated from bone matrix induces bone formation. Mesenchymal cells in bone marrow are determined for development into cartilage and bone cells and only an unspecific stimulus, such as trauma or autotransplantation, is sufficient for the development into mature osteogenic tissue. Mesenchymal cells will not differentiate into bone cells unless stimulated by a specific inductive substance, bone morphogenetic protein (BMP). Implanted to a heterotopic site, BMP induces undifferentiated mesenchymal cells into a bone morphogenetic pathway of development, causing heterotopic bone formation. The quantitative inductive response is dependent on the source of the BMP, and the bone formation is also determined by the recruitment of inducible target cells and by the environment at the implantation site. Hence, the environment at the implantation site is of major importance for the amount of bone formed. BMP initiates a cascade of events that is modulated by endocrine and paracrine factors. The heterotopic bone has all the morphologic and biochemical characteristics of orthotopic bone, is subjected to turnover, and even has the intriguing ability to generate the formation of bone marrow. Experimental induction of heterotopic bone has become a most useful method to study osteoneogenesis and has supplied important information on the prerequisites for new bone formation and on the regulation of bone metabolism. PMID- 1899634 TI - Induced bone development in transplants of fresh human pseudomalignant heterotopic ossification tissue in athymic nude mice. AB - Biopsy specimens of mature trabecular bone from tumors of two typical cases of pseudomalignant heterotopic ossification (PHO; myositis ossificans circumscripta) were transplanted into athymic nude mice. Specimens of normal metaphyseal bone in adjacent areas were also transplanted in the contralateral hindquarter muscles for controls. By seven days, control bone transplants were necrotic and enveloped in granulation tissues whereas PHO transplants were surrounded by proliferating connective tissue derived from the host-bed muscle tissues. In the intervals from 14 and 21 days, the PHO transplants showed vascular and hypertrophied connective tissue proliferation with appositional deposits of new bone. The microscopic features of the new bone suggested that it was of mouse host-bed origin because the new bone from Case 1, a female, showed nuclei without sex chromatin. The quantities of new bone were measured by correlated histomorphometric and computer image analysis of microradiographs. Little or no cartilage development was noted at any stage. The normal control trabecular bone tissue was slowly resorbed by macrophages and mononuclear phagocytes; multinucleated giant cells were few and relatively small. Except in one questionably small area of one transplant, nontumorous undemineralized normal human bone failed to induce bone formation within the 28-day period of observation. The quantity of new bone formed in athymic mice in response to implants of PHO, estimated from equivalent quantities of bone developed from implants of lyophilized matrix-free bone morphogenetic protein (BMP) was about 1 microgram/g of wet PHO tumor weight. Although circumstantial evidence implicates BMP in the pathogenesis of heterotopic ossification, more research should be directed toward regional and systemic factors inhibiting bone development in normal and abnormal conditions, including malignant bone tumors. PMID- 1899635 TI - A clinical perspective on common forms of acquired heterotopic ossification. AB - The clinical courses of heterotopic ossification (HO) as a consequence of trauma and central nervous system insults have many similarities as well as dissimilarities. Detection is commonly noted at two months. The incidence of clinically significant HO is 10%-20%. Approximately 10% of the HO is massive and causes severe restriction in joint motion or ankylosis. The most common sign and symptom are decreased range of motion and pain. The locations are the proximal limbs and joints. Sites of HO about a joint may vary according to the etiology of the HO. Roentgenographic evolution of HO occurs during a six-month period in the majority of patients. Treatment modalities include diphosphonates, indomethacin, radiation, range of motion exercises, and surgical excision. Surgical timing differs according to etiology: traumatic HO may be resected at six months; spinal cord injury HO is excised at one year; and traumatic brain injury HO is removed at 1.5 years. A small number of patients have progression of HO with medicinal treatment and recurrence after resection. The patients seem recalcitrant to present treatment methods regardless of the HO etiology. PMID- 1899636 TI - Efficacy of oral streptokinase-streptodornase in the treatment of ankle sprains. AB - To evaluate the analgesic and antiinflammatory properties of oral streptokinase streptodornase (SS) in cases of minor trauma, 190 patients with ankle sprains were studied. Subjects were randomly given an active drug or a placebo in doses of two tablets three times a day for eight days. A scoring system was used to rate the following symptoms: spontaneous pain, mobilization pain, wearing pain, articular disability, flaccidity, muscular spasm, edema, and hematoma. Each symptom was categorized as none (0), mild (1), moderate (3), or severe (4). Patients were evaluated at the beginning of the study and on the fourth and eighth days of treatment. At the end of the trial, the decrease in each symptom score was significantly greater in patients receiving SS than in patients receiving a placebo. Analgesic intake during the study was also noticeably lower in the SS group. The incidence of drug-induced side effects (mainly abdominal discomfort) was minimal. Oral SS ameliorates the inflammatory symptoms associated with ankle sprains and therefore may be used as an alternative to nonsteroidal antiinflammatory drugs. PMID- 1899637 TI - Periarticular heterotopic ossification after total hip arthroplasty. Risk factors and consequences. AB - The formation of periarticular heterotopic bone after total hip arthroplasty is a frequent complication. The reported occurrences concerning this complication vary considerably in different reports, ranging from 15% to 90% with significant amounts in 1%-27% of the cases. Heterotopic ossification (HO) starts with the surgical operation, and the extent is well delineated on roentgenograms after six to 12 weeks. The amount of bone varies from small islands in the soft tissue to widespread bridging ossification. The cause of HO seems to be mainly related to systemic factors and is chiefly dependent on gender, diagnosis, and concurrent antiinflammatory medication. Patients at risk seem to be those with HO after a previous surgical operation, patients suffering from certain types of ankylosing spondylitis, otherwise healthy men with osteoarthrosis, patients with hypertrophic osteoarthrosis, and patients operated upon for fresh fractures or other posttraumatic conditions. The surgical technique and the local tissue trauma probably moderate both the occurrence and amount of HO. HO does not seem to cause pain or to decrease hip muscle strength but does limit hip mobility in cases with significant amount of ossification. PMID- 1899638 TI - Surgical approaches for resection of heterotopic ossification in traumatic brain injured adults. AB - The site of heterotopic ossification (HO) at the elbow or the hip dictates the surgical approach for resection. Three approaches are used for HO resection at the elbow: (1) a posterolateral approach for posterolateral HO; (2) an anterolateral approach for anterior HO; and (3) a medical approach for medial or posteromedial HO or anterior transfer of the ulnar nerve. Two approaches are recommended for resection of HO at the hip: (1) an anterior approach for anterior or inferomedial HO and (2) a posterior approach for posterior HO. Posterior HO is often associated with a hip-flexion contracture, and an anterior soft-tissue release may be necessary as well. Physical examination indicates the prognosis for functional improvement as well as recurrence. Patients with a near normal neurologic recovery have minimal to no HO recurrence with improved limb function and increased joint motion, whereas a poor neurologic recovery and persistent spasticity are associated with recurrence of HO and no functional limb improvement. Standard roentgenograms aid in selecting the appropriate surgical approach. Radiation, indomethacin, and diphosphonates have been administered for prophylaxis. Physical therapy is necessary until range of motion stabilizes. PMID- 1899639 TI - Experience with surgical resection of heterotopic bone in spinal cord injury patients. AB - Extensive heterotopic ossification may occur after a spinal cord injury. Surgical removal of the heterotopic bone is considered only in patients who develop limitations of function or related skin pressure areas. In a prospective study of 21 patients, a total of 43 surgical procedures were performed to resect heterotopic bone. Long-term follow-up study was available for 18 patients who had 38 surgical procedures. This was a descriptive study since preoperative, surgical, and postoperative care varied slightly over time and were dependent on newer advances in surgical techniques and therapeutic agents. Primary complications included excessive bleeding, infection, fractures, and recurrence of the heterotopic ossification. Procedures are outlined that may reduce the incidence of postoperative infection. Fractures are related to the degree of regional osteoporosis. Recurrence is still a common problem, and any or all therapeutic agents that may reduce the extent of postoperative recurrence should be considered before surgical excision is planned. PMID- 1899640 TI - Total hip arthroplasty. The role of antiinflammatory medications in the prevention of heterotopic ossification. AB - Postoperative prophylaxis with antiinflammatory medications, primarily indomethacin, is extremely effective in preventing the severest degrees of heterotopic ossification (HO) after a total hip arthroplasty (THA) and the recurrence of excised HO developed after a previous hip surgery. Prophylaxis with indomethacin should be given in 25-mg doses three times daily for at least three weeks, starting on the first postoperative morning. However, a shorter treatment period may be equally effective in preventing the severest degrees of HO, and a postoperative delay of five days before the initiation of prophylaxis does not seem to be followed by the development of severe HO. As evaluated one year after surgery, treatment with antiinflammatory medications in the immediate postoperative weeks did not increase the incidence of implant-bone interface radiolucencies, aseptic loosening, or revisions in cemented or cementless THAs when compared with cases that did not have postoperative treatment. However, although no major complications have been reported regarding the use of antiinflammatory medications in the prevention of HO after THA, orthopedic surgeons prescribing such treatment should be aware of their contraindications as well as early and late side effects. Since several antiinflammatory agents are reported to be effective in preventing HO, future reports dealing with HO after THA should always include information about the postoperative antiinflammatory treatment used. PMID- 1899641 TI - Prevention of heterotopic ossification in high-risk patients by radiation therapy. AB - Heterotopic ossification (HO) is a frequent occurrence after cemented and cementless total hip arthroplasty (THA). Patients at risk for this complication include those with preexisting ipsilateral or contralateral HO, diffuse idiopathic skeletal hyperostosis, hypertrophic osteoarthrosis, posttraumatic arthritis, and ankylosing spondylitis. Low-dose radiation therapy effectively prevents HO in this high-risk group when treatment is begun early in the postoperative period. A prospective evaluation has established the efficacy of fractionated and single-dose radiation therapy protocols. Limited radiation portals are used in patients receiving cementless prostheses. A rectangular radiation portal obliquely oriented to the prosthesis enables radiation treatment of the periarticular soft tissues while avoiding exposure of the bone-prosthesis interface. Radiation therapy to this interface may inhibit or delay bony ingrowth. Radiation therapy is the only treatment used to prevent HO that is delivered locally and not systemically. Low-dose radiation therapy using a limited radiation portal is the treatment of choice to prevent HO in high-risk patients after cementless THA. PMID- 1899642 TI - Heterotopic bone formation in thermal burns. AB - Heterotopic bone is a rare complication of burns. The factors to be considered in its development are the percentage of burn, the location of burn, the length of bed confinement, osteoporosis, superimposed trauma, and genetic predisposition. Characteristically, heterotopic bone develops between one and three months after the acute burn. It may continue to proliferate as long as there are open wounds but it tends to regress once the burn wound has healed. If it has bridged a joint it may be surgically excised after the burn has healed. The more extensive the heterotopic bone the poorer the prognosis for restoration of motion after excision. Prevention of heterotopic bone appears to be linked in part to early mobilization of the patient and recovery from the postburn hypermetabolic and catabolic state. PMID- 1899643 TI - [Acute lead poisoning]. AB - A 36-year-old woman had for two months experienced progressively more marked diffuse abdominal pain, at times colicky, as well as nausea, vomiting and severe constipation. In addition, paraesthesias and motor weakness developed in the thighs. This was accompanied by a normochromic, normocytic anaemia with a haemoglobin concentration of 9.6 g/l. A short time later her mother and daughter also fell ill with similar symptoms. After symptomatic treatment had failed, secondary coproporphyria due to lead poisoning was found. The poisoning had resulted from criminal contamination of food, especially of cocoa powder, with lead acetate. Raised lead concentrations in serum were found in two other members of the family. In all the patients treatment was undertaken with sodium calcium edetate (20 mg/kg body-weight) in several three-day cycles, achieving a gradual fall in serum lead concentration. When the level had fallen to below 4 mumol/l the symptoms disappeared. Below 3 mumol/l porphyria was no longer demonstrable and the anaemia regressed. It is pointed out that, as lead poisoning may be fatal, it should be considered in the differential diagnosis of acute abdominal colic of unclear cause. PMID- 1899644 TI - [Transdermal nitroglycerin systems with continuous and discontinuous drug release. A comparison of the anti-ischemic and hemodynamic acute and long-term effects]. AB - The anti-ischaemic and haemodynamic effects of two transdermal nitroglycerin systems, each offering 15 mg of nitroglycerine, the first giving continuous release (group 1) and the other discontinuous release (group 2), were compared in 30 men (mean age 56.5 [33-70] years) with coronary heart disease confirmed by angiography. Resting and exercise haemodynamics together with the degree of exercise-induced ST segment depression were measured on the first day, before and two hours after application of the plaster. After one week's therapy these measurements were repeated 24 hours after the application of the plaster on the previous day and two hours after the last application. Two hours after the first application both groups showed significant reduction (P less than 0.01) in exercise-induced ST segment depression (group 1: -60%, group 2: -50%) and in mean pulmonary artery pressure during exercise (group 1: -10%; group 2: -7%). After one week's therapy the reduction in exercise-induced ST segment depression was still significant in group 1 (-60%; P less than 0.01), but in group 2 (-30%) it was no longer significant. After one week had passed there was no longer any significant reduction in mean pulmonary artery pressure in either group (group 1: -6%; group 2: 0%). The acute anti-ischaemic and haemodynamic efficacy of both transdermal nitroglycerin systems was hence comparable; however, the emergence of nitrate tolerance during long-term use was not prevented even by phased release of the drug. PMID- 1899645 TI - The epidemiological relationship between Salmonella isolated from poultry meat and sewage effluents at a long-stay hospital. AB - Between February 1988 and March 1989 chicken carcases delivered to the kitchen of a long stay psycho-geriatric hospital were screened every week for salmonella contamination. While 214 of 477 (45%) individual carcases carried one or more salmonella types, every single consignment examined contained affected carcases. Simultaneously, sewers draining the residential accommodation and excluding kitchen effluent, were also monitored. Thirty out of 79 (38%) of Moore's swabs were positive for salmonella. There was a statistically significant association between the salmonella types isolated from chicken and those isolated from sewers the following week. Following a change in kitchen policy to order only cooked chicken there was a significant reduction in the isolation of salmonella from the sewers. PMID- 1899646 TI - Meningococcal carriage in close contacts of cases. AB - Between 1 October 1986 and 31 March 1987, 55 cases of meningococcal disease were identified in the South-West of England, an attack rate of 1.54 per 100,000 during the study period. Antibiotics used in the treatment of the disease successfully eliminated nasopharyngeal carriage of meningococci in 13 out of 14 cases without use of rifampicin. The overall meningococcal carriage rate in 384 close contacts was 18.2% and the carriage rate of strains indistinguishable from the associated case strain was 11.1%. The carriage rate of indistinguishable strains in household contacts (16.0%) was higher than the carriage rate in contacts living at other addresses (7.0%, P less than 0.05). A 2-day course of rifampicin successfully eradicated meningococci from 46 (98%) of 47 colonized contacts. In one third of cases groupable meningococci were isolated from at least one household contact; 92% of these isolates were of the same serogroup as the associated case strain. When a meningococcus is not isolated from a deep site in a clinical case of meningococcal disease, culture of serogroup A or C strains from nasopharyngeal swabs of the case or of household contacts is an indication that the close contact group should be offered meningococcal A + C vaccine in addition to chemoprophylaxis. The failure in this and other studies to isolate meningococci from any household contact in the majority of cases may be due either to the relative insensitivity of nasopharyngeal swabbing in detecting meningococcal carriage or to the acquisition of meningococci by most index cases from sources outside the household. PMID- 1899647 TI - Genetic relationships among strains of Neisseria meningitidis causing disease in Italy, 1984-7. AB - Since 1984 a change in the epidemiological pattern of meningococcal disease in Italy has occurred with a predominance of Neisseria meningitidis of serogroup C (76%), serotype 2a and a high proportion of strains resistant to sulphonamides (71%). In order to understand better the epidemiology of the group C N. meningitidis strains responsible for the disease over the last years in Italy, we studied the genetic features of phenotypically closely related strains, by enzyme electrophoresis. The results showed that the genetic and the phenotypic characteristics of the 57 strains studied were similar, suggesting that spread of a single clone during recent years in our country. This result is in agreement with the circulation of strains typical of epidemic situations, despite the decreasing incidence of meningococcal disease in Italy. PMID- 1899648 TI - Trypanosoma cruzi: aberrant expression of class II major histocompatibility complex molecules in skeletal and heart muscle cells of chronically infected mice. AB - In isolated skeletal, heart, and smooth muscle cells from BALB/c and C3H/HeJ mice infected with different strains of Trypanosoma cruzi the presence of class II MHC molecules was investigated by immunocytochemical techniques. We employed single muscle fibers instead of conventional cryostat sections to obtain a more accurate antigen localization. Approximately half of the skeletal muscle cells isolated from the rectus femoris expressed Ia antigens on their surface, irrespective of the mouse or parasite strain combination. Ia expression was apparent only at 30 days postinfection and thereafter. The heart muscle cells expressed class II molecules only at 1 and 3 months postinfection. In no case did the smooth muscle cells from infected mice express Ia antigens. Studies of the same molecules in the noninfected animals gave constantly negative results. We conclude that in the course of the chronic infection of mice with T. cruzi, ectopic expression of class II MHC molecules occurs at the surface of skeletal and heart muscle cells, providing a possible mechanism for explaining the anti-striped muscle autoreactivity present in Chagas' disease. PMID- 1899649 TI - The histone H1-lacZ' fusion protein produced in Escherichia coli binds to the 5' TTGGCAnnnTGCCAA-3' motif on DNA. AB - The coding region of the chicken histone H1.03 gene was cloned to a bacterial expression vector, and the 291-amino acid H1-beta-galactosidase fusion protein was isolated after induction with IPTG. The fusion protein recognizes the 5' TTGGCAnnnTGCCAA-3' motif on DNA. The H1 globular domain was initially shown to be responsible for the sequence-specific binding by functional deletion analysis. This function may be indispensable for the role of H1 as a determinant of nucleosome positioning and as a eukaryotic repressor. PMID- 1899650 TI - Characterization of G proteins in rat myometrium. A differential modulation of Gi2 alpha and Gi3 alpha during gestation. AB - Myometrial membranes, obtained from estrogen-dominated (day 0) rat uteri, were immunoblotted with antiserum (SG1), which recognizes the alpha subunits of both Gi1 and Gi2, with antiserum (LE2) specific for Gi2 alpha, and with I3B antiserum, specific for Gi3 alpha. The data revealed the absence of detectable levels of Gi1 alpha and the simultaneous presence of Gi2 alpha and Gi3 alpha as Gi subunits in rat myometrium. The expression of Gi proteins during gestation (days 0, 12, 21) was studied with the above antibodies. No qualitative change in the nature of Gi alpha species was observed during gestation: Gi1 alpha remained undetectable, Gi2 alpha and Gi3 alpha were both present on days 12 and 21. Of significance was the increase (160%) in the amount of Gi2 alpha at midgestation (day 12) compared to days 0 and 21. A different pattern was observed with Gi3 alpha, which decreased with advancing gestation (day 0 greater than 12 greater than 21). Immunodetection of beta subunits of G proteins indicated the presence of a 35/36 kDa doublet on days 0, 12 and 21, with an increase at midgestation. The simultaneous increase in Gi2 alpha and beta subunits may provide an explanation for the previously demonstrated alteration in adenylate cyclase stimulability detected at midgestation. PMID- 1899651 TI - Cytotoxic potential despite impaired activation pathways in T lymphocytes infiltrating nasopharyngeal carcinoma. AB - Nasopharyngeal carcinoma (NPC) is an epithelial tumor consistently associated with EBV. The histological picture is characterized by a strikingly abundant lymphocytic infiltrate. Furthermore, the epithelial tumor cells present several immunological characteristics which suggest an important role for tumor infiltrating lymphocytes (TIL) in the biology of this tumor. The present study reports the phenotypic and functional characterization of TIL from NPC obtained after enzymatic digestion of 15 NPC biopsies. Flow cytometric analysis of TIL suspensions indicated that most TIL were mature CD3+ T lymphocytes (mean = 60%) with a variable CD4/CD8 ratio. Most TIL were TCR alpha/beta-positive (mean = 55%) and only a few TCR gamma-delta-positive cells could be identified. A small percentage (mean = 9%) displayed an activated phenotype (CD25+, HLA class II+). Using limiting dilution analysis, we found that the average frequency of proliferative T-lymphocyte precursors (PTL-P) is lower among TIL (1/40) than in autologous (1/7) or normal PBL (1/1.4). Moreover, sorting experiments have shown that this defect is significantly more pronounced in the CD8+ than in the CD4+ TIL subset. Accordingly, the TCR and the CD2-mediated antigen-independent pathways of activation were impaired. Different types of cytotoxic precursor could be detected. These included lectin-dependent cell cytotoxicity (LDCC) and NK-like or lymphokine-activated killer (LAK) activity. Interestingly, some TIL from NPC were able to lyse an NPC tumor (C15) maintained in nude mice. Thus, despite impaired activation pathways, the cytolytic potential of proliferating TIL in NPC is preserved. PMID- 1899652 TI - The role of plasminogen activators in alopecia areata. AB - Plasminogen activators are serine proteinases which transform the serum zymogen, plasminogen, into plasmin, a broad-spectrum protease with fibrinolytic effect. Two main plasminogen activators have been described in humans: urokinase (UK; molecular weight, 55,000) and tissue-type plasminogen activator (tPA; molecular weight, 74,000). Thirteen subjects were studied who had alopecia areata (AA), nine in the active phase and four in remission. There were alterations in the perivascular and peribulbar fibrinolytic activity in the nine subjects in the active phase of disease, suggesting a possible role of plasminogen activators in AA. A modified Todd's autohistographic method was used to evaluate cutaneous fibrinolytic activity (which depended on the activity of plasminogen activators) in the 13 AA subjects and five volunteer controls. Cutaneous fibrinolytic activity was reduced in perivascular areas, but increased in peribulbar areas, in the nine subjects in the active phase of disease. Tests with monoclonal antibodies directed against the catalytic sites of tPA and UK showed that the perivascular fibrinolytic activity was tPA dependent, and the peribulbar fibrinolytic activity was UK dependent. PMID- 1899653 TI - Immunolocalization of tissue plasminogen activator in the diabetic and nondiabetic retina and choroid. AB - Retinal capillary closure is a common finding in many patients with diabetic retinopathy. The cause of this capillary occlusion is unknown. Since occlusions in microthromboembolic disease can occur because of deficiencies in tissue plasminogen activator (tPA) and since systemic tPA decreases with an increasing duration of diabetes mellitus, the immunohistochemical localization of tPA in the retinas and choroids of diabetic and nondiabetic patients was investigated. The localization of tPA was confined to arteries and arterioles in peripheral retinas from nondiabetics. Both veins and arteries were positive in these choroids. Two of three noninsulin-dependent diabetics had normal levels of immunoreactivity in their retinas, and all had normal levels of immunolocalization in their choroids. All but 2 of the 12 insulin-dependent diabetic eyes (IDDM), however, had reduced levels of retinal tPA immunoreactivity which was most pronounced in their peripheral retinas. Seven eyes from patients with IDDM had no reaction product in their peripheral retinas. Two such eyes also had reduced tPA immunoreactivity in their choroidal vessels. Some tPA-positive vessels were observed in the central retinas of these eyes, but the number of positive vessels and amount of reaction product was greatly reduced compared with eyes from nondiabetic patients. These observations suggest that IDDM patients have reduced fibrinolytic activity in their retinas, which might predispose them to thromboembolic disease. PMID- 1899654 TI - Heterogeneous induction of major histocompatibility complex class II antigens on corneal endothelium by interferon-gamma. AB - The expression and distribution of major histocompatibility complex (MHC) class II gene products, HLA-DR, HLA-DQ, and the HLA-DR invariant chain, were studied on flat mounts of human corneal endothelial cells (HCEC) after in vitro incubation of donor corneas with interferon-gamma (IFN-gamma), interleukin-1 (IL-1), and IL 6, using a sensitive immunoperoxidase technique with monoclonal antibodies. Control HCEC and endothelium treated with IL-1 or IL-6 completely lacked MHC class II antigens. After treatment with 50 U/ml, 100 U/ml, 500 U/ml, and 5000 U/ml of human IFN-gamma, a mosaic-like, patchy staining for all MHC class II products was observed: part of the HCEC showed membranous and/or cytoplasmic positivity; other endothelial cells were negative. In addition, a dose-dependent response to IFN-gamma was observed: the proportion of cells expressing class II products rose with increasing doses of IFN-gamma. The induction of MHC class II antigen expression on HCEC by IFN-gamma was completely inhibited by the addition of a neutralizing antibody directed to IFN-gamma but not by IL-1 beta. The significance of these findings with respect to corneal transplantation immunology is discussed. PMID- 1899655 TI - Intensive short-term home care for chronic illness. AB - The revised Medicare regulations offer home health nurses new opportunities to try different visit plans, including more visits. Providing intensive services for a relatively short period of time early in the service period can offer long term benefits for patients and their families as well as overall cost savings for the insurer. PMID- 1899656 TI - Results of the 1983 patterns of care process survey for definitive breast irradiation. AB - This report has documented the U.S.A. national averages for the results of the Process Survey for the 1983 Patterns of Care Study (PCS) for the processes of evaluation, work-up, and treatment for definitive breast irradiation. All women had been treated with definitive irradiation following breast-conserving surgery for early stage breast cancer. The data were collected from 191 patient charts which were randomly selected from five strata of radiotherapy practice to represent the U.S.A. national averages. Clinical and pathological characteristics of the primary tumor and regional lymph node status were similar to reported series as of 1983. Analysis of this Process Survey showed high compliance with the 1983 PCS standards of best current management of breast cancer. However, there was a wide variation in the technical delivery of the radiation fields and radiation doses used. There was good compliance with the use of documentation of the radiation treatments with simulation films, port films, implant films, and field descriptions. No systematic difference was seen amongst the various strata of radiotherapy practice. Although compliance with the majority of the parameters was relatively high, the small but important areas of lack of compliance with the standards of best current management document an incomplete transfer of technology to the radiation oncology community as a whole in 1983. Separate analysis for the outcome of treatment for these cases will be necessary to correlate process with outcome. PMID- 1899657 TI - Intraoperative electron beam radiation therapy (IOEBRT) for carcinoma of the exocrine pancreas. AB - The abdominal cavities of 50 patients were explored in a specially constructed intraoperative radiotherapy operating amphitheater at the Medical College of Ohio. Twenty-six patients were treated with intraoperative and postoperative precision high dose external beam therapy, 12 with intraoperative irradiation but no external beam therapy, and 12 with palliative surgery alone. All but two patients completed the postoperative external beam radiation therapy as initially prescribed. The median survival time for patients treated with palliative surgery alone was 4 months, and that for patients treated with intraoperative radiotherapy without external beam therapy was 3.5 months. Patients undergoing intraoperative irradiation and external beam radiation therapy had a median survival time of 10.5 months. Four patients died within 30 days of surgery and two patients died of gastrointestinal hemorrhage 5 months posttreatment. PMID- 1899658 TI - Computer-CT planning of the electron boost in definitive breast irradiation. AB - Treatment planning of the electron boost in breast irradiation at this institution is performed by using information from CT scanning and from surgical clips used to define the tumor bed. A refinement of this technique, taking into account the surgical axis of approach, using computer-CT planning is now implemented. The location of the scar and the clips are digitized using a computer to define the tumor bed dimensions. With 3-D computer software a line, simulating the surgical axis and the central ray of the electron beam, is drawn between the deepest clip and the surgical scar. This beam's eye view along the surgical axis is projected onto a screen as a starting point. Appropriate gantry angle, treatment table position, beam energy, and precise shaping of the electron field borders with a 2 cm margin around the clips and the scar are determined. Simulation films comparing clinically set-up fields and computer-CT planned fields were reviewed. In only 5 of 17 patients did the clinically set-up field have adequate inclusion of the tumor bed within the treatment volume. Computer-CT planned fields ensured adequate inclusion of the tumor bed in all, including the remaining 12. In 7 patients obvious increased sparing of normal breast tissue was seen with computer-CT planned fields. This technique enables accurate placement of a shaped electron field and further refinement of electron boost treatment planning. This is especially true in situations in which the tumor bed is located at a site distant from the lumpectomy scar rather than directly beneath it and in cases where the tumor bed lies deep within the breast. PMID- 1899659 TI - To boost or not to boost, and how to do it. PMID- 1899660 TI - To boost, why and how. PMID- 1899661 TI - Comparison of 1 vs 2 or more intracavitary brachytherapy applications in the management of carcinoma of the cervix, with irradiation alone. AB - Four hundred ninety-eight patients treated in the USA in 1978 for cancer of the cervix by external beam and intracavitary irradiation have been studied to determine the effect of using a single intracavitary (IC) application versus more than one. Most of the patients (46%) underwent intracavitary (IC) treatment after external radiation therapy (RT), 40% during external RT, and 14% prior to external RT. Five-year actuarial survival for all stages was 66% for greater than or equal to 2 applications versus 59% for 1 application, p less than .01. When survival was analyzed by stage, there was a trend toward improved survival with greater than or equal to 2 applications in Stage II (p .10). The rate of infield recurrence for all stages was higher in the 1 IC group (30% vs 17%, p less than .01). These were more frequent in the 1 IC group (53% vs 34%, p less than .05), in Stage III patients, but no significant difference was noted in the other stages. Distant metastases were more frequent in the 1 IC group (19% vs 11%, p .01). The incidence of major complications was the same in both groups. An analysis of patient characteristics and other variables that would explain the difference in results revealed that older patients (p .03), worse Karnofsky (p .056), and more parametrial involvement (p less than .01) accrued more in the 1 IC group. Higher paracentral point doses were administered when greater than or equal to 2 IC applications were used (p less than 0.01); this group also received higher bladder and rectal doses and lower whole pelvic doses. The use of two or more intracavitary insertions affords an opportunity to administer higher paracentral point doses, which appear to be related to higher pelvic tumor control, lower rate of distant metastasis, and better survival. PMID- 1899662 TI - Carbon dioxide binding to human hemoglobin cross-linked between the alpha chains. AB - The binding of carbon dioxide to human hemoglobin cross-linked between Lys alpha 99 residues with bis(3,5-di-bromosalicyl) fumarate was measured using manometric techniques. The binding of CO2 to unmodified hemoglobin can be described by two classes of sites with high and low affinities corresponding to the amino-terminal valines of the beta and alpha chains, respectively (Perrella, M., Kilmartin, J. V., Fogg, J., and Rossi-Bernardi, L. (1975b) Nature 256, 759-761. The cross linked hemoglobin bound less CO2 than native hemoglobin at all CO2 concentrations in deoxygenated and liganded conformations, and the ligand-linked effect was reduced. Fitting the data to models of CO2 binding suggests that only half of the expected saturation with CO2 is possible. The remaining binding is described by a single affinity constant that for cross-linked deoxyhemoglobin is about two thirds of the high affinity constant for deoxyhemoglobin A and that for cross linked cyanomethemoglobin is equal to the high affinity constant for unmodified cyanomethemoglobin A or carbonmonoxyhemoglobin A. The low affinity binding constant for cross-linked hemoglobin in both the deoxygenated and liganded conformations is close to zero, which is significantly less than the affinity constants for either subunit binding site in unmodified hemoglobin. Comparing the low affinity sites in this modified hemoglobin to native hemoglobin suggests that cross-linking hemoglobin between Lys alpha 99 residues prevents CO2 binding at the alpha-subunit NH2 termini. PMID- 1899663 TI - Determination of alpha-subunit contact regions of human follicle-stimulating hormone beta-subunit using synthetic peptides. AB - Follicle-stimulating hormone (FSH) is a glycoprotein hormone composed of two different subunits designated FSH-alpha and FSH-beta. Using synthetic peptides corresponding to the primary structure of human (h) FSH-beta subunit, we previously identified two regions of the beta-subunit, hFSH-(33-53) and hFSH-(81 95), as receptor binding regions. In this report, we tested the ability of synthetic peptides to interact with hFSH-alpha-subunit. Synthetic peptides corresponding to hFSH-beta-(11-25), (41-55), (51-65), and (101-111) were able to bind specifically radioiodinated hFSH-alpha-subunit, suggesting that they represent regions of interaction with the alpha-subunit. These experimental results were in agreement with the location of alpha-subunit contact regions predicted by sequence analysis. Peptides of hFSH-beta-subunit showing maximum specific binding to the alpha-subunit were those possessing minimum interaction with receptor whereas those not binding to alpha-subunit corresponded to regions shown to interact with receptor (hFSH-beta-(33-53) and hFSH-beta-(81-95]. The hFSH-beta-subunit, therefore, seems to have two discontinuous receptor binding regions flanked by three alpha-subunit contact regions. PMID- 1899664 TI - Three-dimensional structure of the elastase of Pseudomonas aeruginosa at 1.5-A resolution. AB - Pseudomonas aeruginosa elastase (PAE) is a zinc metalloprotease with 301 amino acids. We have crystallized and solved the three-dimensional structure of PAE, using data to 1.5-A resolution, and have refined the native molecular structure to R = 0.188. The overall tertiary structure of the PAE molecule is similar to that of thermolysin, with which it shares 28% amino acid sequence identity. Nearly all of the active site residues that might potentially interact with substrates are identical in the two proteins. However, the active site cleft is significantly more "open" in PAE than in thermolysin. PMID- 1899665 TI - Role of the C-terminal region of smg p21, a ras p21-like small GTP-binding protein, in membrane and smg p21 GDP/GTP exchange protein interactions. AB - Limited proteolysis with trypsin of smg p21B, a ras p21-like small GTP-binding protein having the same putative effector domain as ras p21s, produced the N terminal fragment and the C-terminal tail of Lys-Lys-Ser-Ser-geranylgeranyl-Cys methyl ester. The Mr values of the intact smg p21B, the N-terminal fragment, and the C-terminal tail were estimated to be about 22,000, 20,500, and less than 1,000, respectively, by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Both the GDP- and GTP-bound forms of the intact smg p21B bound to various membranes and phosphatidylserine-linked Affi-Gel. However, both the GDP- and GTP-bound forms of the N-terminal fragment failed to bind to membranes and phosphatidylserine-linked Affi-Gel. In contrast, the C-terminal tail bound to membranes and phosphatidylserine-linked Affi-Gel. The N-terminal fragment contained a GDP/GTP-binding and GTPase domain and exhibited these two activities, but the C-terminal tail did not show any such activity. A GTPase-activating protein for smg p21 stimulated the GTPase activity of both the intact smg p21B and the N-terminal fragment. In contrast, a GDP/GTP exchange protein for smg p21, named GDP dissociation stimulator, stimulated the GDP/GTP exchange reaction of the intact smg p21B but not that of the N-terminal fragment. These results indicate 1) that smg p21B is composed of at least two functionally different domains, the N-terminal GDP/GTP-binding and GTPase domain and the C-terminal membrane-binding domain, 2) that smg p21B binds to membranes through its C terminal hydrophobic and basic domain, and 3) that this C-terminal domain is also essential for the smg p21 GDP dissociation stimulator action but not for the smg p21 GTPase-activating protein action. PMID- 1899666 TI - Incidence of heterotopic ossification after total hip replacement: effect of the type of fixation of the femoral component. AB - The incidence and severity of heterotopic ossification after sixty-five consecutive primary uncemented total hip replacements were compared with those after seventy consecutive primary hybrid total hip replacements (consisting of an uncemented acetabular component and a cemented femoral component). All patients had had the arthroplasty because of osteoarthrosis. The sex distribution, prevalence of bilateral disease of the hip, and frequency of previous operations were similar in both groups. All of the operations were performed by one surgeon who used the same operative approach. Preoperative, immediate postoperative, and six-month follow-up radiographs were reviewed for all patients. For 90 per cent of the hips, radiographs that were made after a minimum follow-up of one year were also reviewed. In the group of patients who had an uncemented femoral component, there was a statistically significant increase in the frequency of heterotopic bone and in its severity. Either none or only class-I ectopic bone developed in 74 per cent of the hips in the hybrid group, compared with 40 per cent of the hips in the uncemented group (p less than 0.005). In contrast, class III or IV heterotopic ossification was evident in 13 per cent of the hips in the uncemented group (p less than 0.005). None of the patients in the hybrid group needed reoperation for excision of ectopic bone, but four (6 per cent) of the patients in the uncemented group needed such a reoperation because of severe limitation of motion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1899667 TI - Total hip replacement with cemented, uncemented, and hybrid prostheses. A comparison of clinical and radiographic results at two to four years. AB - One hundred and thirty-one patients who had 144 cemented or uncemented hip prostheses were followed prospectively for two to four years. A cemented or a hybrid prosthesis (consisting of a cemented femoral component and an uncemented acetabular component) was used in men older than seventy years, in women older than sixty years, and in younger patients in whom adequate initial fixation could not be obtained without cement. Uncemented, porous-surfaced implants were used in all other patients. The over-all clinical results were similar for the three groups. For the fifty-two hips that had a cemented prosthesis, the mean total Harris hip rating was 91 points and the score for pain, 42 points; for the twenty seven hips that had a hybrid prosthesis, 90 and 43 points; and for the sixty-five hips that had an implant allowing ingrowth of bone in both the acetabulum and the femur, 95 and 43 points. Two prosthetic stems that were designed to allow ingrowth of bone had aseptic loosening; one was revised. Pain in the thigh, usually slight and not disabling, occurred at one year in 24 per cent of the patients in whom a femoral component allowing ingrowth had been used; the prevalence of pain then declined. The incidences of migration of the components and of radiolucent lines were greater in the acetabula that had a cemented component than in those that had a cup allowing ingrowth of bone. PMID- 1899668 TI - Spatial and temporal control of nonmuscle myosin localization: identification of a domain that is necessary for myosin filament disassembly in vivo. AB - Myosin null mutants of Dictyostelium are defective for cytokinesis, multicellular development, and capping of surface proteins. We have used these cells as transformation recipients for an altered myosin heavy chain gene that encodes a protein bearing a carboxy-terminal 34-kD truncation. This truncation eliminates threonine phosphorylation sites previously shown to control filament assembly in vitro. Despite restoration of growth in suspension, development, and ability to cap cell surface proteins, these delta C34-truncated myosin transformants display severe cytoskeletal abnormalities, including excessive localization of the truncated myosin to the cortical cytoskeleton, impaired cell shaped dynamics, and a temporal defect in myosin dissociation from beneath capped surface proteins. These data demonstrate that the carboxy-terminal domain of myosin plays a critical role in regulating the disassembly of the protein from contractile structures in vivo. PMID- 1899670 TI - Narcolepsy--attitudes and amphetamines. PMID- 1899669 TI - Genetically modified yolk proteins precipitate in the adult Drosophila fat body. AB - Ultrastructural and genetic studies were carried out on the fat body of a female sterile mutant fs(1)1163 to ascertain why yolk protein 1 (YP1) is not secreted from this tissue. Earlier molecular studies demonstrated that (a) normally yolk protein is synthesized in the fat body, secreted into the hemolymph and taken up by the ovary, (b) the 1163 mutation causes a single amino acid substitution in YP1, and (c) females homozygous for the mutation, or heterozygous females raised at 29 degrees C, retain YP1 in the fat body. Ultrastructural analysis in this paper shows that the fat body of these females contains masses of electron-dense material deposited in the subbasement membrane space. This subbasement membrane material (SBMM), which occasionally has a crystalline-like, fibrous component, is found in females whose genotypes include at least one copy of the mutant 1163 gene. These strains include a deletion strain that is hemizygous for the 1163 gene and two strains that are transgenic for the mutant gene. Immunogold studies indicate that SBMM contains yolk protein. We propose that the mutant protein is secreted into the subbasement membrane space, but because of the amino acid substitution in YP1, the oligomers containing YP1 condense into SBMM, which cannot penetrate the basement membrane. The similarity of SBMM and deoxyhemoglobin S fibers is discussed. PMID- 1899671 TI - Endoscopy in upper GI bleeding. PMID- 1899672 TI - Hypercalcemia of occult origin. PMID- 1899673 TI - Radiculopathy in an elderly woman. PMID- 1899674 TI - Helicobacter pylori and duodenal ulceration. PMID- 1899676 TI - Screening for hearing impairment in the elderly. PMID- 1899675 TI - Aortic dissection: diagnosis and management. AB - Acute dissections mandate surgery after the patient has been stabilized medically. Hypertension appears to be a prerequisite in the pathogenesis of aortic dissection, and control of ventricular contraction velocity may be prophylactic. PMID- 1899677 TI - Applying the science of disease prevention. PMID- 1899678 TI - Role of solid media when used in conjunction with the BACTEC system for mycobacterial isolation and identification. AB - This study evaluated the necessity and the contribution of solid media when used in conjunction with radiometric Middlebrook 7H12 (BACTEC 12B; Becton Dickinson, Towson, Md.) medium for recovery and complete identification of mycobacteria. Each of 1,184 digested, decontaminated respiratory specimens was inoculated into one BACTEC 12B vial, one 7H11 plate, and two Lowenstein-Jensen (LJ) slants. When the 12B vial was smear positive for acid-fast bacilli, the organisms were subcultured onto LJ slants and the BACTEC p-nitro-alpha-acetylamino-beta hydroxypropiophenone (NAP) test system was inoculated with the organisms. Niacin tests were performed by using the growth from the original LJ slants and organisms from the LJ slants subcultured from 12B or 7H11 medium. The times to achieve definitive NAP and niacin test results were recorded. Recovery of all 143 isolates found in this study could not be achieved with a single medium. Among the three media, the highest percentage (92.8%) of Mycobacterium tuberculosis isolate recovered was with BACTEC 12B. The use of either 7H11 medium or LJ slants along with a 12B vial increased by 4 to 6% the total percentage of M. tuberculosis organisms that were isolated. Isolation of the M. tuberculosis complex and NAP differentiation in 12B medium were completed in an average of 17 days. On average, isolation and definitive niacin test results for M. tuberculosis cultures were obtained in 39.3 days by a conventional procedure and in 36.3 days when 12B subcultures were used. These results support the conclusion that LJ slants contribute 4 to 6% increased recovery of M. tuberculosis when used in conjunction with 12B medium. Additionally, a subculture onto LJ slants from 12B medium yielded sufficient growth for niacin testing earlier than an original LJ slant did. PMID- 1899679 TI - Cellular fatty acid composition as an adjunct to the identification of asporogenous, aerobic gram-positive rods. AB - Cellular fatty acid (CFA) compositions of 561 asporogenous, aerobic gram-positive rods were analyzed by gas-liquid chromatography as an adjunct to their identification when grown on blood agar at 35 degrees C. The organisms could be divided into two groups. In the first group (branched-chain type), which included coryneform CDC groups A-3, A-4, and A-5; some strains of B-1 and B-3; "Corynebacterium aquaticum"; Brevibacterium liquefaciens; Rothia dentocariosa; and Listeria spp., the rods had sizable quantities of antiesopentadecanoic (Ca15:0) and anteisoheptadecanoic (Ca17:0) acids. Other species with these types of CFA included B. acetylicum, which contained large amounts of isotridecanoic (Ci13:0) and anteisotridecanoic (Ca13:0) acids. CFAs useful for distinguishing among Jonesia denitrificans, Oerskovia spp., some strains of CDC groups B-1 and B 3, Kurthia spp., and Propionibacterium avidum were hexadecanoic (C 16:0) acid, isopentadecanoic (Ci15:0) acid, and Ca15:0). The second group (straight-chained type), which included Actinomyces pyogenes; Arcanobacterium haemolyticum; C. bovis; C. cystitidis; C. diphtheriae; C. flavescens, "C. gentalium"; C. jeikeium; C. kutscheri; C. matruchotii; C .minutissimum; C. mycetoides; C. pilosum; C. pseudodiphtheriticum; "C. pseudogenitalium"; C. pseudotuberculosis; C. renale; CDC groups 1, 2, ANF-1, D-2, E, F-1, F-2, G-1, G-2, and I-2; C. striatum; "C. tuberculostearicum"; C. ulcerans; C. vitarumen; C. xerosis; and Erysipelothrix rhusiopathiae, was typified by significant quantities of hexadecanoic (C16:0) and oleic acids (C18:cis9), with differences in the amounts of linoleic acid (C18:2), stearic acid (C18:0), an unnamed peak (equivalent chain length, 14.966), and small quantities of other known saturated and unsaturated fatty acids. CFA composition of these organisms was sufficiently discriminatory to assist in classification but could not be used as the sole means of identification. PMID- 1899681 TI - Concurrent nitroglycerin administration decreases thrombolytic potential of tissue-type plasminogen activator. AB - Dynamic coronary vasoconstriction may play a role in coronary artery reocclusion after successful thrombolysis. The effect of nitroglycerin on the thrombolytic effects of recombinant tissue-type plasminogen activator (rt-PA) was examined in dogs with an electrically induced occlusive coronary artery thrombus. Eleven dogs were randomly given rt-PA alone and seven rt-PA with nitroglycerin. The dose of rt-PA was 0.75 mg/kg body weight given over 20 min and the dose of nitroglycerin was 125 micrograms/min for 40 min. The reperfusion rate in the dogs given rt-PA alone was 73% (8 of 11 dogs) and that in the rt-PA plus nitroglycerin group was 57% (four of seven dogs) (p = NS). The time to thrombolysis (or reperfusion) in dogs receiving rt-PA plus nitroglycerin was 70% greater than in those receiving rt-PA alone (means +/- SD/29.8 +/- 9.9 versus 17.6 +/- 5.9 min, p less than 0.02), and the duration of reperfusion much shorter (11 +/- 17 versus 42 +/- 16 min, p less than 0.02). Peak coronary blood flow after reperfusion in dogs receiving rt-PA plus nitroglycerin was also less than in those receiving rt-PA alone (36 +/- 52 versus 63 +/- 20 ml/min, p less than 0.02). Reocclusion occurred in all dogs given rt-PA with nitroglycerin and in six of eight given rt-PA alone (p = NS). Plasma concentrations of rt-PA were lower when nitroglycerin was given with rt-PA alone (427 +/- 279 versus 1,471 +/- 600 ng/ml, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1899680 TI - Heart rate variability in patients with ventricular arrhythmias: effect of antiarrhythmic drugs. Antiarrhythmic Drug Evaluation Group (ADEG). AB - The purpose of this study was to investigate whether heart rate variability could be reliably assessed in patients with ventricular arrhythmias and to evaluate whether it is affected by antiarrhythmic drugs. The study was based on an analysis of 239 ambulatory electrocardiographic (ECG) recordings obtained from 67 patients with frequent and complex ventricular arrhythmias enrolled in the Antiarrhythmic Drug Evaluation Group (ADEG) study. In each recording, after exclusion of premature ventricular complexes, the number of times during a 24 h period in which two consecutive sinus RR intervals differed by more than 50 ms was calculated. The total 24 h count from each recording was then used as an index of heart rate variability. This method is a reliable marker of cardiac parasympathetic activity. Recordings were analyzed at baseline (n = 56), during long-term treatment with amiodarone (n = 17), flecainide (n = 22) or propafenone (n = 17) and after washout in selected patients (n = 5). Despite the presence of a different number of arrhythmias, total 24 h counts in the same patient appeared reproducible over time (r = 0.83 between two different recordings, n = 49, p less than 0.0001). Baseline counts (median 1,698, range 26 to 13,648) were not correlated (r = 0.15) with the number of arrhythmias. The three antiarrhythmic drugs had a disparate effect on total 24 h counts: no change was observed in patients treated with amiodarone (median percent change [delta %]-8, p = NS), whereas a significant (p less than 0.025) decrease occurred in patients treated with flecainide (median delta % -56%) or propafenone (median delta % 64%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1899683 TI - Pet projects: animal assisted therapy in nursing homes. AB - 1. Animal assisted therapy is an applied science using animals to solve a human problem. It is an interdisciplinary approach using animals as an adjunct to other therapies. 2. The major difference between animals as therapy and entertainment is the animal-human bond, a special relationship that develops when a person has strong feelings of psychological attachment to the animal. 3. It is essential that a complete nursing and activity assessment be made before implementation of individualized animal assisted therapy. PMID- 1899682 TI - Catecholamine responses to histamine infusion in man. AB - To evaluate the effects of histamine-induced hypotension on plasma catecholamine levels, eight normal men, aged 20 to 40 years, were infused with incremental doses of histamine starting at 0.2 microgram/kg/min at a 30 degree tilt position with monitoring of blood pressure (BP) and heart rate. Histamine dosage was increased every 5 minutes by 0.1 to 0.2 microgram/kg/min until mean BP fell greater than 15 mm Hg or a dosage of 1.6 micrograms/kg/min was reached. Plasma catecholamine samples were taken between the fourth and fifth minute of each histamine dosage. Identical measurements were made during nitroglycerin-induced hypotension in these subjects. Histamine produced threefold greater increases in heart rate and plasma norepinephrine (NE) levels than did nitroglycerin for comparable decreases in BP. Although NE levels increased twofold to fivefold from baseline with histamine infusion, epinephrine levels increased minimally at the highest doses or not at all. Our data demonstrate that histamine selectively releases NE from adrenergic nerve terminals without significant adrenal catecholamine release. We suggest that neural NE release plays an important role in the cardiac effects of histamine. PMID- 1899685 TI - Localization of urokinase-type plasminogen activator messenger RNA in the normal mouse by in situ hybridization. AB - The histological distribution of urokinase-type plasminogen activator (u-PA) mRNA was analyzed in normal mouse tissue by in situ hybridization with anti-sense RNA transcribed from three different subclones of a mouse u-PA cDNA. Hybridization signal was found over a distinct fibroblast-like cell in the lamina propria of the gastrointestinal tract, over proximal, distal, and collecting tubules of the kidney, and over the epithelium of the bladder, ductus deferens, and epididymis. No hybridization signal was found over cells of the lung, pancreas, liver, adrenal, pituitary, cerebrum, hypothalamus, cerebellum, sciatic nerve, and striated muscle, nor over endothelial cells in any tissue investigated. The lack of u-PA mRNA in lung tissue was confirmed by Northern analysis and is in contrast to the high amounts of u-PA protein found in this tissue. PMID- 1899684 TI - Subcellular localization of N-acetylglucosaminide beta 1----4 galactosyltransferase revealed by immunoelectron microscopy. AB - We prepared a monoclonal antibody (MAb) against N-acetylglucosaminide beta 1----4 galactosyltransferase purified from F9 embryonal carcinoma cells. The MAb recognized the protein portion of the enzyme, since it inhibited galactosyltransferase activity, reacted with the enzyme both from F9 cells and from bovine milk, and did not exhibit anti-carbohydrate activity. Using this MAb, we studied the subcellular localization of the enzyme by immunoelectron microscopy. Intense staining was observed in trans-Golgi stacks within testicular interstitial cells and mucous neck cells, confirming the specificity of the immunological reaction. Cell surface galactosyltransferase was detected in the following regions: cultured cells such as F9 embryonal carcinoma cells, testicular interstitial cells, seminiferous tubule epithelial cells, Sertoli cells, the head of the epididymal sperm, epididymal epithelial cells, and apical surfaces of epithelial cells in the fundic gland and of intestinal goblet cells. The use of Triton X-100 intensified the cell surface immunoreactivity, and in certain cases the mode of distribution of the cell surface enzyme was different from that described in previous reports. In addition, nuclear envelopes of cultured cells were distinctly stained. The possible significance of the latter finding is discussed in relation to recent advances in nuclear localization of glycoproteins. PMID- 1899686 TI - Developmental regulation of the intrathymic T cell precursor population. AB - The maturation potential of CD4-8- thymocytes purified from mice of different developmental ages was examined in vivo after intrathymic injection. As previously reported, 14-day fetal CD4-8- thymocytes produced fewer CD4+ than CD8+ progeny in peripheral lymphoid tissues, resulting in a CD4+:CD8+ ratio of less than or equal to 1.0. In contrast, adult CD4-8- thymocytes generated CD4+ or CD8+ peripheral progeny in the proportions found in the normal adult animal (CD4+:CD8+ = 2 to 3). Here we have shown that CD4-8- precursor cells from the 17-day fetal thymus also produced peripheral lymphocytes with low CD4+:CD8+ ratios. Precursors from full term fetuses produced slightly higher CD4+:CD8+ ratios (1.1-1.6) and precursors from animals three to 4 days post-birth achieved CD4+:CD8+ ratios intermediate between those produced by fetal and adult CD4-8- thymocytes. Parallel changes in the production of alpha beta TCR+ peripheral progeny were observed. Fetal CD4-8- thymocytes generated fewer alpha beta TCR+ progeny than did adult CD4-8- thymocytes. However, peripheral lymphocytes arising from either fetal or adult thymic precursors showed similar proportions of gamma delta TCR+ cells. The same pattern of progeny was observed when fetal CD4-8- thymocytes matured in an adult or in a fetal thymic stromal environment. In contrast to fetal thymic precursors, fetal liver T cell precursors resembled adult CD4-8- thymocytes by all parameters measured. These results suggest that fetal thymic precursors are intrinsically different from both adult CD4-8- thymocytes and fetal liver T cell precursors. Moreover, they lead to the hypothesis that the composition of the peripheral T cell compartment is developmentally regulated by the types of precursors found in the thymus. A model is proposed in which migration of adult-like precursors from the fetal liver to the thymus approximately at birth triggers a transition from the fetal to the adult stages of intrathymic T cell differentiation. PMID- 1899687 TI - Frequency analysis of IgE-secreting B lymphocytes in persons with normal or elevated serum IgE levels. AB - The immunoregulatory mechanisms that determine the high serum IgE antibody levels in disorders such as helminth parasite infections and the hyper-IgE recurrent infection syndrome (HIE) remain poorly understood. To assess whether elevated serum IgE levels result from an increased number of B lymphocytes committed to IgE production, the proportion of IgE-producing B lymphocytes was determined by a filter immunoplaque assay using PBMC from persons with a broad range of serum IgE levels that included normal persons (n = 9) and patients with loiasis (n = 12), tropical pulmonary eosinophilia (TPE) (n = 6), lymphatic filariasis (n = 28), and HIE (n = 8). PBMC from these persons were assessed for production of in vitro IgE. The geometric mean number of IgE-secreting cells in 10(5) B lymphocytes in PBMC was 0.42 (range 0-2.2) in normal persons, 5.6 (range 0.1-35.5) among patients with loiasis, 9.4 (range 0-53.2) among patients with lymphatic filariasis, 52 (range 31.5-115) among patients with TPE, and 218 (range 56-1404) among patients with HIE. When all study subjects were grouped, there were significant correlations with serum IgE levels (r2 = 0.78; p less than 0.0001) and net spontaneous in vitro IgE production (r2 = 0.8; p less than 0.0001). Estimates of the amount of IgE production per B lymphocyte were similar among normal persons, patients with filarial infections, and patients with TPE (geometric means of 134, 96, and 141 pg/ml/cell, respectively); in contrast, for HIE patients, IgE production by individual B cells was significantly lower (geometric mean 28 pg/ml/cell; p less than 0.001). These observations demonstrate that clonal expansion of IgE-producing B lymphocytes is a major mechanism underlying the elevated serum IgE levels seen in persons with hyper-IgE states. PMID- 1899688 TI - T and B cell responses to myelin-oligodendrocyte glycoprotein in multiple sclerosis. AB - The pathogenesis of multiple sclerosis (MS) is believed to involve an autoimmune component directed against the myelin sheath. One potential target Ag for such autoimmune attack is the myelin-oligodendrocyte glycoprotein (MOG) because an anti-MOG mAb has profound influence on the course of experimental autoimmune encephalomyelitis, which to some extent represents an experimental model of MS. Using single cell assays, we have evaluated T and B cell reactivities to MOG in MS patients and controls. T cell reactivity was estimated by counting the number of cells that secreted IFN-gamma in response to MOG, whereas B cell reactivity was estimated by enumerating cells secreting antibodies that bound to MOG. MOG reactive T cells were detected in the peripheral blood of the majority of the 16 MS patients examined (mean 1/7299 mononuclear cells), but infrequently and at lower numbers in samples from neurologic controls. MOG-reactive T cells were more frequent among MS patients' cerebrospinal fluid (CSF) mononuclear cells (mean 1/450 cells). The T cell response to MOG was evidently MHC class II restricted, because Fab fragments of a rabbit polyclonal anti HLA-DR antibodies abrogated the Ag-induced increase in number of cells that secreted IFN-gamma, as analyzed on CSF and PBMC from three patients with MS. Anti-MOG IgG antibody-secreting cells were detected in blood in 8 of 16 MS patients (mean 1/25,641 cells), but they were also strongly accumulated in CSF, being detected in 8 of 10 MS patients examined (mean 1/265 cells), while rarely found in controls. The findings imply that MOG may represent a pathogenetically important target Ag in MS. PMID- 1899689 TI - Clearance of t-PA, PAI-1, and t-PA-PAI-1 complex in an isolated perfused rat liver system. AB - The role of physiologic inhibitors of tissue-type plasminogen activator (t-PA) in its clearance has not yet been defined. In this study, the clearance of t-PA, plasminogen activator inhibitor 1 (PAI-1), and t-PA-PAI-1 complex was determined in an isolated perfused rat liver system. The clearance of t-PA-PAI-1 complex was twice as fast as that of t-PA, whereas PAI-1 was cleared slowly. The half-lives for t-PA, determined by a two-compartmental pharmacokinetic model, were: alpha, 20.1 minutes, and beta, 120.0 minutes. The corresponding values for t-PA-PAI-1 complex were: alpha, 9.7 minutes, and beta, about 7 hours. The model microconstants were computed for t-PA and t-PA-PAI-1 complex and the marked difference between the "on" microconstants k12 for t-PA (0.026 +/- 0.001 min-1) and t-PA-PAI-1 complex (0.090 +/- 0.025 min-1) suggests that the effect on binding to liver cells is the most important factor in the faster clearance of t PA-PAI-1 complex when compared with t-PA. PMID- 1899691 TI - Analysis and quantitation of the beta-amyloid precursor protein in the cerebrospinal fluid of Alzheimer's disease patients with a monoclonal antibody based immunoassay. AB - One of the major clinical findings in Alzheimer's disease (AD) is the formation of deposits of beta-amyloid protein in amyloid plaques, derived from the beta amyloid precursor protein (beta-APP). To determine the possible use of beta-APP as a diagnostic marker for AD in CSF, a monoclonal antibody-based immunoassay specific for this protein was developed. The assay does not differentiate between beta-APP695 and beta-APP751 forms but does preferentially recognize beta-APP751 complexed with a protease. Of the two sets of CSF samples tested, one set, obtained from living patients, gave a slightly lower level of beta-APP in AD and Parkinson's disease patients relative to controls, whereas the other set, composed of postmortem samples, showed no significant differences between the AD and control groups. PMID- 1899690 TI - Variation in the characteristics of 10 mouse-passaged scrapie lines derived from five scrapie-positive sheep. AB - Ten mouse-passaged scrapie lines were initiated from five sheep with clinical scrapie. Of the lines, five were initiated and passaged exclusively in mice with the s7s7 genotype and the remaining five lines were initiated in mice with the p7p7 genotype, with two of these lines subsequently being passaged exclusively in p7p7 mice and two being passaged mainly in p7p7 mice. Lines were passaged three or four times and two parameters were compared: incubation period and the induction of a weight increase during the preclinical period. Considerable variation in the incubation periods was found between the different passage lines at similar passage levels, with a range in s7s7 mice of 113 days to greater than 450 days and a range in p7p7 mice of 219 days to greater than 500 days. All of the lines passaged exclusively in s7s7 mice had shorter incubation periods in this mouse genotype than in p7p7 mice, whereas of the five lines initiated in p7p7 mice, two had shorter incubation periods in p7p7 mouse strains. C57BL mice were used as the indicator strain and most of the lines caused an increase in weight during the preclinical phase of disease compared to control mice injected with normal brain homogenates. For both parameters, incubation period and preclinical weight increase, differences were seen in lines that had identical passage histories, suggesting that an informational molecule separate from host genomic material must specify scrapie strain differences. PMID- 1899692 TI - Preproenkephalin mRNA and methionine-enkephalin increase in mouse striatum after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine treatment. AB - Dopaminergic neurons that project to the striatum from the substantia nigra are thought to modulate methionine-enkephalin (Met-Enk) metabolism in the striatum. We administered a dose of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) that produces a moderate depletion of dopamine in striatum, about 50%, without overt motor deficits, and found that Met-Enk-like immunoreactivity and preproenkephalin mRNA content increased in the tissue. Pretreatment with the monoamine oxidase B inhibitor deprenyl or the dopamine transport blocker nomifensine prevented these changes, suggesting that the changes were related to the partial loss of dopaminergic neurons rather than to MPTP. Moreover, administering GM1 ganglioside, which partially restores the MPTP-induced dopaminergic deficit, partially corrected the Met-Enk changes in the striatum as well. These findings are consistent with the hypothesis that dopaminergic input to the striatum, in part, modulates Met-Enk metabolism. Moreover, they show that moderate nigrostriatal lesions are sufficient to elevate Met-Enk and preproenkephalin mRNA contents and that restoration of dopaminergic function, as in our studies with GM1 ganglioside, restores the content of Met-Enk. PMID- 1899693 TI - Differential effects of angiotensin II and eledoisin on monoamine oxidase A and B activities in rat brain. AB - Intracerebroventricular injections of angiotensin II caused 108, 62, and 54% increases in monoamine oxidase A activities in rat hippocampus, hypothalamus, and striatum, respectively. These activatory effects were abolished by simultaneous injections of eledoisin. No significant changes of monoamine oxidase B activities were found under the same experimental conditions. Neither angiotensin II nor elodoisin changed substrate/inhibitor affinities of both isoenzymes. These data indicate that angiotensin II and tachykinin transmitter systems may exert opposite, long-term regulatory effects on monoaminergic neurons in rat brain. PMID- 1899694 TI - Acute regional cerebral blood flow changes caused by severe head injuries. AB - To evaluate the changes in cerebral blood flow (CBF) that occur immediately after head injury and the effects of different posttraumatic lesions on CBF, 61 CBF studies were obtained using the xenon-computerized tomography method in 32 severely head-injured adults (Glasgow Coma Scale score (GCS) less than or equal to 7). The measurements were made within 7 days after injury, 43% in the first 24 hours. During the 1st day, patients with an initial GCS score of 3 or 4 and no surgical mass had significantly lower flows than did those with a higher GCS score or mass lesions (p less than 0.05): in the first 1 to 4 hours, those without surgical mass lesions had a mean CBF of 27 cc/100 gm/min, which rose to 44 cc/100 gm/min by 24 hours. Patients without surgical mass lesions who died tended to have a lower global CBF than did those with better outcomes. Mass lesions were associated with a high global CBF and bihemispheric contusions with the lowest flows. By 24 hours after injury, global blood flow increased in groups that originally had low flows and decreased in those with very high initial flows, such that by 36 to 48 hours, most patients had CBF values between 32 and 55 cc/100 gm/min. Lobar, basal ganglion, and brain-stem blood flow values frequently differed by 25% or more from global averages. Brain-stem CBF varied the most but did not correlate with clinical signs of brain-stem dysfunction. Double studies were performed at two different pCO2 values in 10 patients with various posttraumatic lesions, and the CO2 vasoresponsivity was calculated. Abnormal CO2 vasoresponsivity was found with acute subdural hematomas and defuse cerebral swelling but not with epidural hematomas. In patients without surgical mass lesions, the findings suggest that CBF in the first few hours after injury is often low, followed by a hyperemic phase that peaks at 24 hours. Global CBF values vary widely depending on the type of traumatic brain injury, and brain stem flow is often not accurately reflected by global CBF values. These findings underscore the need to define regional CBF abnormalities in victims of severe head injury if treatment is intended to prevent regional ischemia. PMID- 1899695 TI - Delivery of ultraviolet-inactivated 35S-herpesvirus across an osmotically modified blood-brain barrier. AB - The present studies were undertaken to determine if viral particles can be delivered across the rat blood-brain barrier (BBB). Osmotic BBB modification with intracarotid mannitol (25%) was immediately followed by bolus intracarotid administration of 0.5 ml purified, ultraviolet-inactivated, herpes simplex virus type 1 endogenously labeled with 35S-labeled methionine (2.0 x 10(6) cpm, approximately 5 x 10(8) plaque-forming units/ml). After 60 minutes, intravascular virus was cleared by saline perfusion and the animals were sacrificed. A marked increase (fourfold, p less than or equal to 0.02) in radioactivity was observed in the ipsilateral brain hemisphere when compared to control animals without barrier modification. Administration of intravenous virus immediately after BBB modification displayed no difference in delivery when compared to intracarotid saline-infused controls (without BBB modification) suggesting the importance of a first-pass phenomenon. There were no significant differences in serum concentrations among intracarotid or intravenous groups. These preliminary studies suggest the possibility of delivering viral particles across the BBB with osmotic disruption, which may permit delivery of genetic material in replication defective viral vectors in the feline model of GM2-gangliosidosis. PMID- 1899697 TI - A cost-effective, unit-based approach to computerized care planning education. AB - This article describes a grassroots approach to developing an educational program on nursing diagnosis and computerized care planning. The process involved staff nurses in program design, implementation, and evaluation. Using this process, staff development educators will be better able to successfully initiate grassroots programs that educate large numbers of nurses at minimal cost. PMID- 1899696 TI - Biological significance of tissue plasminogen activator content in brain tumors. AB - Fresh brain-tumor samples were obtained at operation and analyzed for their content of tissue type plasminogen activator (tPA) using an activity assay (gel chromatography zymogram) and an enzyme-linked immunospecific assay. The specimens were taken from 23 glioblastomas, 35 metastatic tumors, 42 meningiomas, 16 low grade gliomas, and seven acoustic neurinomas; seven specimens were from normal brain. A strong correlation was found between the results of the two assays (r = 0.77, p less than 0.0001). There was a threefold difference in the tPA content of the benign tumors as compared to malignant tumors (p = 0.0006), the latter having less tPA. Histologically benign meningiomas contained higher tPA than malignant meningiomas (p = 0.01); however, the difference between low-grade gliomas and high-grade gliomas was less evident. Overall regression analysis data have shown an inverse relationship between the tissue content in tPA and the presence and degree of tumor necrosis and peritumoral brain edema (p = 0.004 and p = 0.0004, respectively). This finding was most consistent in the glioblastoma group where the correlation coefficient values were r = 0.53 and r = -0.55, respectively. There was no significant correlation between the tissue tPA content and the age and sex, steroid use, or plasma tPA of the patients or the duration of symptoms. In summary, this is the first demonstration of tPA in a large series of human brain tumors and in normal brain. The differences observed have clear biological significance and, although the source of tPA in tumor tissue is still unknown, a relative reduction in tPA in tumor tissue may play an integral role in the development of tissue necrosis and tissue edema. The lack of tPA in tumor necrosis was not due to tissue destruction and cell death since urokinase was readily detectable in that tissue. PMID- 1899698 TI - The nursing care technician program. An education process for nurse extenders. AB - The Nursing Care Technician Program at Ochsner Foundation Hospital in New Orleans, Louisiana, is specifically designed to enable the nurse to plan, provide, and evaluate patient care while delegating tasks to assistive personnel. This article describes the institution's approach to role development, reviews the planning, implementation, and evaluation process, and provides an analysis of associated costs, benefits, and patient outcomes of the program. PMID- 1899699 TI - Host factors and early therapeutic response in acute otitis media. AB - To evaluate the relationship between eradication of bacterial infection and clinical improvement in children with otitis media, we reviewed the clinical outcome of bacterial otitis media in patients enrolled in double-blind trials of antibacterial therapy from 1979 to 1988. Cultures of middle ear exudates showed the distribution of bacterial pathogens to be similar to that observed in other geographic areas. Two hundred ninety-three patients had otitis media caused by bacterial pathogens and underwent repeat tympanocentesis after 3 to 6 days of therapy. Bacteriologic success was demonstrated in 253 patients (86%); 40 patients (14%) had bacteriologic failure. Children who had bacteriologic failure were younger than those with bacteriologic success (median age 10.6 vs 18.5 months; p = 0.001); 38% of patients who had bacteriologic failure were black, compared with 18% of patients with bacteriologic success (p = 0.007). Gender, history of frequent otitis media, and presence of bilateral otitis media were not risk factors for bacteriologic failure. Clinical success was demonstrated in 261 patients (89%); 32 patients (11%) had clinical failure. Agreement between clinical and bacteriologic response was 86% (95% confidence interval: 81.6% to 89.6%). Ninety-three percent (236/253) of subjects whose infection was eliminated had clinical resolution, whereas 37% (15/40) of those with bacteriologic failure had persisting symptoms or signs of clinical failure. We conclude that failure to eliminate bacteria from the middle ear is often associated with persistent signs and symptoms. Bacteriologic failure affects children less than 18 months of age almost exclusively. Bacteriologic and clinical failure are frequently discordant; mechanisms unrelated to the bacterial infection may explain some of the persisting clinical signs. PMID- 1899700 TI - Fetal supraventricular tachycardia treated with flecainide acetate. PMID- 1899701 TI - RP 49356 and cromakalim relax airway smooth muscle in vitro by opening a sulphonylurea-sensitive K+ channel: a comparison with nifedipine. AB - RP 49356 is a novel compound which relaxes airway smooth muscle in vitro. Like cromakalim, RP 49356 reduced contractility in guinea pig isolated trachealis under basal conditions or when challenged with low (less than 20 mM) but not high K+. These effects were antagonized by the sulphonylureas glibenclamide and glipizide. This spectrum of action is typical of the class of compounds known as potassium channel openers (KCOs). Unlike RP 49356 and cromakalim, nifedipine had no effect on basal tone, relaxed tissues contracted with low or high K+ and was not antagonized by the sulphonylureas. These data suggest that the KCOs are not acting directly at the voltage-gated Ca++ channel in this tissue. RP 49356 and cromakalim were similar to nifedipine by being more potent at relaxing tissues precontracted with carbachol or histamine (spasmolytic effects) than they were at preventing initiation of the response to these spasmogens (antispasmogenic effects). Because the maintained phase of contraction in airway smooth muscle may be associated with some Ca++ influx, the data presented here suggests that, like nifedipine, the KCOs are more active smooth muscle relaxants under conditions of Ca++ influx. In summary, RP 49356, like cromakalim, is a compound which relaxes airway smooth muscle in vitro by opening a sulphonylurea-sensitive K+ channel which may be similar to the ATP-sensitive K+ channel found in other tissues. PMID- 1899702 TI - The effects of the putative potassium channel activator WAY-120,491 on 86Rb efflux from the rabbit aorta. AB - WAY-120,491 [(-)-(3S-trans)-2-[3,4-dihydro-3-hydroxy-2,2-dimethyl-6-(trifluoromet hox y)- 2H-1-benzopyran-4-yl]-2,3-dihydro-1H-isoindol-1-one] is a novel antihypertensive agent. We have investigated the effects of this compound on contractile force and 86Rb efflux, using the rabbit aorta, in order to assess its K channel activator properties. K channel blockers and ionic conditions thought to modulate specific K channel types have been used to provide insight into the K channel(s) affected by this compound. WAY-120,491 evoked relaxation of precontracted rabbit aortic rings and increased the rate of 86Rb efflux from strips of rabbit aorta; both effects occurring in a concentration-dependent manner. The WAY-120,491 (1 microM)-induced 86Rb efflux was inhibited by tetraethylammonium (IC50 = 0.38 mM), indicating that the increased efflux was mediated by K channels. Glyburide completely blocked the WAY-120,491 (1 microM) evoked 86Rb efflux with 50% block occurring at a concentration of 0.48 microM. Glyburide also antagonized the WAY-120,491-induced relaxation of aortic rings. Omission of Ca from the solution bathing the aorta did not inhibit the WAY 120,491 induced 86Rb efflux but rather caused an augmentation of the response. It is concluded that WAY-120,491 may be classified as a K channel opener. Furthermore, the K channel upon which WAY-120,491 acts exhibits some characteristics normally associated with the ATP regulated K channel although the involvement of other K channel types has not been ruled out. PMID- 1899703 TI - The hemodynamic effects of S-nitrosocaptopril in anesthetized dogs. AB - We studied the effects of a unique vasoactive agent, S-nitrosocaptopril (SnoCap), in an anesthetized canine preparation. We have previously demonstrated that this agent manifests the properties of both a direct nitrovasodilator and an angiotensin-converting enzyme inhibitor in vitro. The present investigation was performed to evaluate the effects of SnoCap in vivo. Intravenous administration of SnoCap produced immediate reductions in blood pressure and significantly attenuated the pressor response to angiotensin I. Equieffective doses of SnoCap had a greater duration of action after intravenous bolus administration compared with nitroglycerin (15.3 +/- 2.6 min vs. 3.2 +/- 0.5 min, respectively; P less than .01); importantly, this effect was apparent despite the relatively short plasma half-life of the compound (T1/2 alpha = 0.48 min, T1/2 beta = 5.54 min) and did not appear to be the result of inhibition of angiotensin-converting enzyme. Another unexpected property of SnoCap was that its nitrovasodilator effect was 10- to 30-fold less potent than nitroglycerin when administered as a bolus, but more efficacious when given by continuous infusion. These data support the view that SnoCap is a vasoactive substance with the properties of a nitrovasodilator and an angiotensin-converting enzyme inhibitor, as well as the unique properties of an extended duration of action and greater potency when administered by continuous intravenous infusion than by bolus injection. The clinical utility of this compound in humans and in individuals with specific disease states remains to be demonstrated. PMID- 1899704 TI - Therapeutic flexibility in the post disaster response. PMID- 1899705 TI - Planning for the aftermath. PMID- 1899706 TI - Onset of ulcerative colitis in a patient with colonic schistosomiasis. PMID- 1899707 TI - Crystal structures at 2.2 A resolution of the catalytic domains of normal ras protein and an oncogenic mutant complexed with GDP. AB - The biological functions of ras proteins are controlled by the bound guanine nucleotide GDP or GTP. The GTP-bound conformation is biologically active, and is rapidly deactivated to the GDP-bound conformation through interaction with GAP (GTPase Activating Protein). Most transforming mutants of ras proteins have drastically reduced GTP hydrolysis rates even in the presence of GAP. The crystal structures of the GDP complexes of ras proteins at 2.2 A resolution reveal the detailed interaction between the ras proteins and the GDP molecule. All the currently known transforming mutation positions are clustered around the bound guanine nucleotide molecule. The presumed "effector" region and the GAP recognition region are both highly exposed. No significant structural differences were found between the GDP complexes of normal ras protein and the oncogenic mutant with valine at position 12, except the side-chain of the valine residue. However, comparison with GTP-analog complexes of ras proteins suggests that the valine side-chain may inhibit GTP hydrolysis in two possible ways: (1) interacting directly with the gamma-phosphate and altering its orientation or the conformation of protein residues around the phosphates; and/or (2) preventing either the departure of gamma-phosphate on GTP hydrolysis or the entrance of a nucleophilic group to attack the gamma-phosphate. The structural similarity between ras protein and the bacterial elongation factor Tu suggests that their common structural motif might be conserved for other guanine nucleotide binding proteins. PMID- 1899708 TI - Isolation, crystallization, crystal structure analysis and refinement of constitutive C-phycocyanin from the chromatically adapting cyanobacterium Fremyella diplosiphon at 1.66 A resolution. AB - Constitutive phycocyanin from cyanobacterium Fremyella diplosiphon (Calothrix sp. PCC 7601) grown in green light, has been isolated and crystallized. The crystals belong to the space group R3 with cell constants a = b = 180.26 A, c = 61.24 A, alpha = beta = 90 degrees, gamma = 120 degrees. The crystal structure has been determined by Patterson search techniques using the molecular model of C phycocyanin from the cyanobacterium Agmenellum quadruplicatum. The asymmetric unit of the crystal cell consists of two (alpha beta)-monomers related by a local dyad. Three asymmetric units are arranged around a crystallographic triad and form an (alpha beta)6-hexamer, the functional unit in the native antenna rod. The initial structure has been refined in a cyclic manner by energy-restrained crystallographic refinement and modelling until the conventional crystallographic R-factor converged at 18.1% with data to a resolution of 1.66 A. The molecular structure resembles closely the C-phycocyanins of Mastigocladus laminosus and A. quadruplicatum. The conformation and configuration of the alpha-84 and beta-84 chromophores is very similar to the corresponding chromophores in the trimeric C phycocyanin of M. laminosus, whereas the beta-155 chromophore differs in configuration with C(4)-Z, C(10)-Z and C(15)-Z compared to C(4)-Z, C(10)-Z, C(15) Z,E. The stereochemistry of the beta-155 chiral centres is C(2)-RC(3)-R and C(31) S, respectively, whereas alpha-84 and beta-84 have C(2)-RC(3)-R and C(31)-R. The amino acid sequences of constitutive and inducible phycocyanin differ mainly in residues located on the surface of the beta-subunits that mediate the inter hexameric contacts. PMID- 1899709 TI - Trauma care reimbursement: comparison of DRGs to an injury severity-based payment system. AB - Concern exists that per case payment using Diagnosis Related Groups (DRGs) inadequately pays trauma centers. In this study, 45 Trauma Resource Groups (TRGs), an alternative patient classification system based on the Injury Severity Score and patient age, is developed and compared to 172 Diagnosis Related Groups (DRGs) that include trauma diagnoses. TRGs were developed using 1983 Maryland trauma patient hospital discharge abstracts (n= 34,702), the same source used to assign a DRG. We compared estimated TRG and DRG payments to actual charges for 17,398 trauma cases treated during 1986 at five trauma centers and 18 community hospitals in the Central Maryland Metropolitan Statistical Area. The unexpected findings of this study are that an anatomic severity-based classification of hospital trauma discharges (TRGs) does not perform as well as DRGs in: 1) explaining variations in length of stay for trauma cases, or 2) assuring an appropriate distribution of revenues to regional trauma centers and community hospitals. Solutions discussed include segregating community hospital and trauma center costs in computation of average per case rate setting, and inclusion of physiologic and mechanism of injury parameters in prospective payment classification systems to increase explained variance of resource use. PMID- 1899710 TI - Preoperative laboratory screening in healthy Mayo patients: cost-effective elimination of tests and unchanged outcomes. AB - We reviewed the results of preoperative screening laboratory tests in asymptomatic healthy patients who underwent elective surgical procedures at our institution in 1988. Substantially abnormal results were found in 160 of 3,782 patients. All such abnormalities involved five tests: aspartate aminotransferase, glucose, potassium, platelet count, and hemoglobin. Thirty of the abnormal test results were predictable on the basis of the history or physical examination. The abnormal test result prompted further assessment in 47 patients. No surgical procedure was delayed, and no association was noted between adverse outcome and any preoperative laboratory abnormality. Because of our findings in this analysis and similar studies on specific tests from other institutions, we no longer require preoperative laboratory screening tests for healthy patients. PMID- 1899711 TI - Evaluating PPO performance using prior expenditure data. AB - Preferred provider organizations (PPOs) have grown dramatically since 1983, a growth that has been spurred by the hope that they will be able to moderate the rate of growth in health care costs. This remarkable growth has taken place despite the small number of empiric studies that have been published evaluating the effectiveness of PPOs in controlling costs. The experience in the first year of operation of a PPO established by an insurance company for the employees and the dependents of a large midwestern manufacturer is reported. It shows that substantial selection effects were observed, with PPO enrollees substantially more likely to be younger, have more and younger dependents, and to be non bargaining-unit employees. Enrollees in the PPO also tended to have substantially lower expenditures in the prior year ($596 vs. $821). The effect of the PPO on expenditures was estimated in multivariate regression models controlling for demographic and prior expenditure differences. PPO enrollees were found to have increased their expenditures substantially (P less than 0.0001). Increased expenditures stemming from expansions in outpatient benefits and ineffective utilization management had swamped the effects of reductions in inpatient expenditures and of discounted fees. PMID- 1899712 TI - Standardizing nursing-home admission dates for short-term hospital stays. AB - In the Institutional Population Component of the 1987 National Medical Expenditure Survey, the definition of a nursing home admission was standardized to ignore the readmission of patients discharged for short-term hospital care. Approximately one out of six persons residing in nursing homes on the survey reference date (January 1, 1987) had been readmitted for this reason. The effect of the standardization was to increase the average length of stay of residents prior to the reference date by approximately 5 months. The percentage of long stay residents, those living in the facility for more than three years, increased from 31% to 36%. The percentage admitted from the community during the previous year increased from 32% of those admitted in 1986 to 41%. PMID- 1899713 TI - Transdermal delivery of levonorgestrel. PMID- 1899714 TI - Role of 5'-deoxy-5'-methylthioadenosine in growth of several microbial B12 requirers. AB - 5'-Deoxy-5'-Methylthioadenosine (MTA) figures in cellular methionine and polyamine syntheses. It replaces B12 for growth of the chrysomonad protozoan Poteriochromonas malhamensis at a ratio of MTA:B12 of approximatly 10,000,000:1 (by weight). MTA does not replace B12 for other B12-requirers, e.g.: Euglena gracilis, Lactobacillus leichmannii, and Escherichia coli 113-3. The methionine synergism for P. malhamensis growth is also negated when B12 activity is annulled by alkali treatment; MTA is not inactivated by such treatment. The growth promoting activity of various deoxynucloesides and deoxynucloetides for P. malhamensis and other B12-requirers is reported here due to contamination by cobalamins. Ethionine antagonizes the growth-enhancing effect of MTA, methionine, and B12, individually and collectively -evidence that MTA plays a role in supplying methionine for P. malhamensis growth. MTA concentrations in body fluids and mammalian tissues are too low to interfere with the use of P. malhamensis for estimating only metabolically active B12. PMID- 1899715 TI - Management of submucous uterine fibroid with buserelin, gemeprost and hysteroscopic resection. AB - A 19-year-old virgin presented with severe menorrhagia and a haemoglobin level of 76 g/L as a problem of management. A 5 cm diameter submucous fibroid was identified at hysteroscopy and biopsied but was unable to be removed. The luteinising hormone releasing hormone agonist, buserelin, was used in an attempt to produce symptomatic relief. One week after commencing buserelin therapy, severe menorrhagia occurred and the patient was admitted to hospital with a haemoglobin concentration of 24 g/L. Buserelin treatment was continued and no further menstruation occurred over the following year. As the patient was now well, hysteroscopic submucous fibroid resection was contemplated. Due to cervical rigidity in this teenager, a 1 mg gemeprost pessary was inserted into the posterior vaginal fornix three hours before surgery. This allowed an operative hysteroscope to be inserted into the uterus and a fibroid resection to be performed. Menstrual blood loss has been normal for six months after hysteroscopy. A combined medical and surgical approach may avoid hysterectomy in such problem patients. PMID- 1899716 TI - Evaluation of the mutagenic potential of the antichagasic drug Rochagan in healthy and chagasic rodents. AB - Benznidazole (bz) is the active component of the antichagasic drug Rochagan. Tests were carried out to detect the induction of chromosomal aberrations and micronuclei in rodent bone marrow cells and peripheral blood cells, respectively. Rats were exposed to acute treatment with Rochagan by gavage at total doses of 150, 300, 1500, 2000 and 3000 mg bz/kg body weight and killed at different times. In the chronic treatments, healthy and chagasic Balb/c mice were treated with Rochagan by gavage at a dose of 100 mg bz/kg/day for 10 and 25 days. No significant increase in frequency of chromosomal aberrations in bone marrow cells or of micronuclei in peripheral blood cells was detected in the animals acutely or chronically exposed to Rochagan in vivo. PMID- 1899717 TI - Aneuploidy in Drosophila, II. Further validation of the FIX and ZESTE genetic test systems employing female Drosophila melanogaster. AB - Two sensitive genetic systems for the detection of germline aneuploidy employing Drosophila melanogaster females were described in the first paper of this series (Zimmering et al., submitted to Mutation Research). Designated FIX and ZESTE, these systems permit the rapid and efficient detection of exceptional offspring derived from aneuploid female germ cells. The current report presents test results from a survey of 8 additional chemicals that have been analyzed in both systems. The tested chemicals include: acetonitrile, cadmium chloride, carbendazim, dimethylsulfoxide (DMSO), methylmercury(II) chloride, methoxyethyl acetate, propionitrile and water. Excluding the negative control, water, only the fungicide carbendazim failed to induce aneuploidy in either test system. Of the remaining 6 chemicals one, methylmercury(II) chloride, was positive in the FIX system but not in ZESTE, while MEA was positive in ZESTE and borderline in FIX. The results provide little evidence of germ-cell stage specificity of response to the tested chemicals. Comparison of the induced rates of aneuploidy i indicates that these can exhibit departures from simple additivity to the spontaneous rates: induced rates in the ZESTE system are generally higher and more variable than those from FIX. Possible reasons for the difference in responsiveness between FIX and ZESTE flies are discussed as is the question of the classification of those chemicals which induce chromosome loss events but not chromosome gains. PMID- 1899718 TI - Aneuploidy in Drosophila, IV. Inhalation studies on the induction of aneuploidy by nitriles. AB - The Drosophila ZESTE system was used to monitor the induction of sex chromosome aneuploidy following inhalation exposure of adult females to four nitriles: acetonitrile, propionitrile, acrylonitrile and fumaronitrile. Acetonitrile and propionitrile were highly effective aneuploidogens, inducing both chromosome loss and chromosome gain following brief exposures to low concentrations of these chemicals, and these nitriles also induced rapid paralysis. Acrylonitrile-induced chromosome loss only but did not induce paralysis. Fumaronitrile, in contrast with the results reported in yeast, was ineffective in inducing chromosome loss or gain. Virtually all exceptional offspring induced by acetonitrile and propionitrile were recovered in the first sampled eggs, corresponding to treated mature oocytes. Additionally, the time interval between treatment and sampling was shown to be important, suggesting rapid loss or detoxification of the nitriles. Genetic analysis demonstrated that most aneuploids resulted from induced segregation errors during the first division of meiosis. Cold treatments were found to be ineffective in enhancing the effects of acetonitrile, suggesting important differences between the Drosophila and yeast aneuploidy detection systems. Possible mechanisms by which nitriles may disrupt chromosome segregation in Drosophila oocytes are considered. PMID- 1899719 TI - Mutagenic activity of certain synthetic steroids: structural requirement for the mutagenic activity in Salmonella and E. coli. AB - Eight steroids, structurally related to cholesterol, were tested for mutagenic activity in the Ames tester strains. All the test compounds were mutagenic without metabolic activation, although metabolic activation markedly enhanced their activity. A significant decrease in the survival of the radiation-sensitive mutants recA and lexA of Escherichia coli was observed as compared to their wild type counterpart in the presence of the steroids. The role of recA and lexA genes gains further support from the lambda prophage induction in the lysogen as well as with Salmonella strains triggering the error-prone SOS response. Structural features which appear to be essential for mutagenic activity in these strains of the steroids are (1) reactive thio, sulfonyl or sulfinyl groups at the 6 position and (2) a halogen group at the 3 position of the steroidal nucleus. The mutagenicity appears to involve the formation of H2O2 as well as superoxide and hydroxyl radicals. PMID- 1899720 TI - Symptomatic diverticulum of the 4th ventricle. AB - A case of symptomatic diverticulum of the 4th ventricle in a 57-year-old man is presented. This clinicopathological observation supports a relationship between ventricular diverticula and ependyma-lined paraventricular cysts. PMID- 1899721 TI - Osteogenic sarcoma arising adjacent to a long-standing ameloblastoma. A case report. AB - Ameloblastoma is an uncommon odontogenic tumor usually occurring in the mandible. Rarely do other primary tumors occur with or arise from ameloblastoma. We describe a patient with simultaneous osteogenic sarcoma of the maxilla and recurrent ameloblastoma. PMID- 1899722 TI - Comparison of antimicrobial and cytotoxic effects of glutaraldehyde and formocresol. AB - The in vitro antimicrobial and cytotoxic concentrations of glutaraldehyde and formocresol were determined. Minimal antimicrobial concentrations of these two agents against selected microbial flora reported in carious primary teeth were 3.125% for glutaraldehyde and 0.75% for formocresol. At a doubling of these concentrations, most organisms, except Candida albicans, Staphylococcus epidermidis, and Streptococcus mutans, were killed by both substances in 30 seconds. Cytotoxicity was evaluated on tissue cultures of pulp fibroblasts and HeLa cells at minimal cidal concentrations and at 10- and 100-fold dilutions. Exposure of pulp fibroblasts and HeLa cells to formocresol and indirect exposure to vapors caused the cells to become atrophic and to form a less dense tissue pattern. Cells directly exposed to glutaraldehyde retained their normal cell shape and tissue pattern, whereas cells indirectly exposed to vapors continued to proliferate. These data showed effective antimicrobial activity at concentrations of 3.125% glutaraldehyde and 0.75% formocresol and suggested that glutaraldehyde may exert a less cytotoxic effect on the immediate and surrounding tissues when used as a pulpotomy agent. PMID- 1899723 TI - Drug trial benefited HIV children. PMID- 1899724 TI - Regulation of the human T-cell response to Schistosoma japonicum egg antigen by concomitant cellular and humoral mechanisms in vitro. AB - Serum-mediated regulation of T-cell responses specific for soluble egg antigen (SEA) of Schistosoma japonicum was tested in human hosts. When we added autologous serum to SEA-specific human T-cell lines (CD3+, 4+, 8-), we observed suppression of T-cell proliferation, and this suppressive activity was detected in the immunoglobulin-G2 (IgG2) subclass. Suppression was dose-dependent and antigen-specific. T-cell proliferation induced by only one SEA fraction of greater than 18 kDa was modulated in the presence of 100 micrograms/ml autologous as well as allogeneic infected IgG2. This SEA fraction-driven proliferation was also regulated by suppressor T-cells through distinct suppressive mechanisms. Our results suggest that T-cell responses to a particular component(s) of SEA are strictly regulated through both cellular and humoral mechanisms in human chronic S. japonicum infection. PMID- 1899725 TI - Monoclonal antibodies identify micronemes and a new population of cytoplasmic granules cross-reacting with micronemes of cystozoites of Sarcocystis muris. AB - Micronemes of cystozoites of Sarcocystis muris were isolated after subcellular fractionation and used for immunization of BALB/C mice. After spleen cells of immunized mice were fused with SP20 myeloma cells, ten different monoclonal antibodies (mAbs) were isolated. These antibodies reacted with antigens whose molecular weight ranged from 16 to greater than 90 kDa. Six mAbs recognized granules of 150-400 nm that were located in the vicinity of the Golgi complex but were not identical with dense granules. Two mAbs (2A3, 3A8) were specific for micronemes of cystozoites as demonstrated by immunoelectron microscopy. However, these antibodies also recognized the population of granules near the Golgi complex. Cross-reactivity between micronemes and a dense granule population has not previously been reported. Host cells that had been contacted by cystozoites showed patchy fluorescence when probed with mAb 2A3. This suggests that microneme antigens could be transferred to the host-cell surface during parasite-host cell interactions. PMID- 1899726 TI - Trypanosoma cruzi: properties of a clone isolated from CL strain. AB - BALB/c mice injected i.p. with 2 x 10(6) metacyclic forms of CL-14, a clone isolated from the CL strain of Trypanosoma cruzi, did not show parasitemia as evaluated by direct blood microscopy examination, hemoculture and xenodiagnosis. Moreover, new-born mice (1-2 days old) injected with culture- or insect-derived CL-14 trypomastigotes also displayed negative parasitemia. No mortality was observed in either group of animals. However, despite this apparent non infectivity, mice injected with clone 14 developed high resistance against a lethal challenge with virulent trypomastigotes. All challenged mice survived and the parasitemia was negative. These results indicate that clone 14 is a very good antigen for the study of acquired immunity in T. cruzi infection and, therefore, a potential candidate for the development of a vaccine against this parasite. PMID- 1899727 TI - Fluoroscopically guided nasoenteric feeding tube placement: results of a 1-year study. AB - Nasoenteric tube feeding is a widely used alternative to parenteral intravenous nutritional support or gastrostomy tube placement. Unmonitored tube passage may result in complications and delays the beginning of tube feedings. The authors studied the results of 882 fluoroscopically guided feeding tube placements in 448 patients in 1 year to determine rates of success and complications, as well as the long-term outcome of this population of patients. Seven hundred sixty-four attempts (86.6%) were successful in positioning the tube distal to the third portion of the duodenum. Four major complications (three fatal arrhythmias and one tracheobronchial injury) were encountered. Only seven patients (2%) experienced aspiration events that were due to positioning of the tube in the distal duodenum. Seventy-seven percent of patients required either one or two tubes; the average "tube life" was 7.8 days. Most repositionings were required because of patient noncompliance or inappropriate administration of solid medications. Fluoroscopically guided nasoenteric tube passage is safe, easily performed, and highly successful, and has resulted in widespread clinical acceptance in our institution. PMID- 1899730 TI - Feeding jejunostomy with endoscopic guidance. PMID- 1899728 TI - Organochlorine pesticides and polychlorinated biphenyls in human adipose tissue. AB - Halogenated organic compounds are highly lipophilic chemicals that are persistent in the environment as a result of their use and chemical stability. Some of these compounds are also present in the environment as metabolites or oxidation products of a parent compound or as by-products formed in the production of chlorinated compounds. Chronic exposure to the general population results mainly through the food chain. Because they are lipophilic, and because many are metabolized slowly, these chemicals tend to concentrate in body fat tissue. This contribution has described these halogenated organic compounds, discussed their use, regulation and prohibition throughout the world, and reviewed published studies on the levels of these chemicals found in the adipose tissue of humans and animals. For many years, residues of halogenated organic compounds have been detected in the human adipose tissue of individuals in a number of countries, including those in Europe, Asia, and Africa, as well as in the U.S. The levels detected have been used as an index of the level of general population exposure of these compounds over time. Over the past two decades, most countries have observed a steady decline of this level of exposure, reflecting a reduction in the use of these compounds, restrictions on or banning of their use, and a corresponding decrease in their environmental levels. The levels of concentrations vary from chemical to chemical as well as from isomer to isomer. Since the use of aldrin and dieldrin has now been banned or restricted in the U.S. and a number of other countries, residue levels have slowly decreased. Mean values in human adipose tissue in the U.S. and some foreign countries ranged from 0.04 to 0.40 ppm for dieldrin. Aldrin was detected only in Argentina and Poland in the 1970s and endrin was not detected anywhere at anytime. By 1978, all products containing BHC registered in the U.S. has been either discontinued or reformulated to incorporate lindane rather than BHC. The potential for exposure to BHC is virtually nonexistent in the U.S.; however, exposure to lindane is possible since products containing this chemical are still marketed, and used particularly in the manufacture of human medicine. DDT was banned for agricultural purposes in the U.S. in 1972, although it is still used elsewhere for public health vector control. Since the decline in use of DDT, however, the average levels of concentration have also declined. Heptachlor, chlordane, and trans-nonachlor (a component of both heptachlor and chlordane) are chlorinated cyclodienes.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1899729 TI - Achilles tendon ossification and fracture. PMID- 1899731 TI - The efficacy of OKT3 in vascular rejection. AB - Sixty-six consecutive biopsies of renal allograft recipients treated with OKT3 monoclonal antibody were reviewed and placed into one of two groups. Group I (29 patients) had evidence of acute vascular and cellular rejection, while group II (32 patients) had cellular rejection but no vascular rejection. In 5 cases, the sample was inadequate to determine if vascular rejection was present or not. The severity of the cellular rejection was graded histologically as mild, moderate, or severe. The severity was equivalent when comparing group I with group II (mild, 17% vs. 10%; moderate, 52% vs. 59%; and severe, 31% vs. 31%). There was no difference in the rejection reversal rate between the two groups (86% vs. 91%). However, at 6 and 12 months there was a higher graft loss in the group with vascular rejection (graft survival 64% vs. 81%, P = 0.13, and 58% vs. 75%, P = 0.08, respectively). The poorest outcome was in those patients with both severe acute cellular rejection and acute vascular rejection (4/9, or 44%). The serum creatinine level was higher both pre- and post-OKT3 therapy and at 1, 6, and 12 months in the group with vascular rejection. In conclusion, OKT3 was equally successful in reversing acute cellular rejection and acute vascular rejection. However, increased graft loss occurred at 6 and 12 months in the group with vascular rejection. PMID- 1899732 TI - Corticosteroid inhibition of the OKT3-induced cytokine-related syndrome--dosage and kinetics prerequisites. AB - The data presented extend to a larger series of 27 consecutive renal allograft recipients treated prophylactically with OKT3 our previous observation that the acute OKT3-induced clinical syndrome is related to massive release in the circulation of some cytokines, among which are tumor necrosis factor and interferon gamma. In addition, a pilot randomized study was set up including 12 consecutive patients receiving high-dose corticosteroid treatment (0.5 g solumedrol) either before or at the same time as the first OKT3 injection. Results confirm that when corticosteroids are given in sufficient amount and, importantly, 1 hr before the first OKT3 injection, they significantly decrease the release of both tumor necrosis factor and interferon gamma. In addition, the pretreatment with corticosteroids may totally abolish the IL-2 release induced by OKT3. Given the key role the massive although transient cytokine release plays in determining the OKT3-induced acute syndrome, these results provide the biological basis supporting a precise kinetics of administration of high-dose corticosteroids to better decrease the severity of the clinical reaction. PMID- 1899733 TI - An improved method for the detection of soluble interleukin 2 receptors in liver transplant recipients by flow cytometry. AB - A new flow cytometric method (FCM) for detection of soluble interleukin 2 receptor (sIL-2R) in serum was established. Using this method, results from one to forty samples can be obtained in less than 2 hr as compared with 5 hr in an ELISA. Comparing over 300 sera samples tested by both methods, we found the FCM to be as specific and sensitive as the ELISA, but even more reproducible. Regression analysis of ELISAt on FCMt showed there is a strong relationship between the two assays and they mimic each other over time. We studied the daily serum levels of sIL-2R by FCM in 18 liver allograft recipients: 7 were in the stable group, 6 in the rejection group, and 5 had both rejection and infection. Low or decreasing sIL-2R levels correlated with absence of rejection. In patients with rejection episodes, a typical elevation of sIL-2R was followed by a rapid decrease of sIL-2R after successful response to rejection therapy. Patients with multiple complications displayed elevated sIL-2R levels. In conclusion, because of its rapid turnover time and accuracy, the FCM has the potential to determine the appropriate timing of post-transplant liver biopsies. PMID- 1899734 TI - Induction of the HTLV-I LTR by Jun occurs through the Tax-responsive 21-bp elements. AB - The HTLV-I LTR is known to be induced by a variety of cellular signals. Tax protein is one potent viral trans-activator of LTR-directed transcription. We demonstrate here that Jun is another transcription factor that can strongly modulate the activity of this LTR. Using deletion and competition studies, the minimal portion of the LTR for Jun activation was found to coincide with the Tax responsive 21-bp elements. In binding experiments, nuclear factors that bound to the HTLV-I 21-bp sequence were competed by an excess of AP-1 motif oligonucleotide. Although the Tax-responsive elements do not contain a strictly conserved AP-1 motif, these findings suggest that they function as AP-1 sites. We found, however, that in cells depleted for AP-1 activity (F9 teratocarcinoma), Tax activation of the HTLV-I LTR was maintained. Thus while Jun/AP-1 may be involved in the basal expression of the HTLV-I LTR, it may not be essential for Tax-mediated activation. PMID- 1899735 TI - Prospective randomized double-blind trial of branched chain amino acid enriched versus standard parenteral nutrition solutions in traumatized and septic patients. AB - The addition of branched chain amino acids (BCAA) to total parenteral nutrition (TPN) solutions of balanced aminoacid composition has been reported to result in improved nitrogen balance, preservation of plasma protein levels, and improved immune function; however, only a few large clinical studies have been performed, yielding conflicting results. We, therefore, studied in a prospective, randomized double blind trial, the effects of BCAA enrichment of an otherwise isonitrogenous and isocaloric TPN solution on plasma protein levels in 101 traumatized and septic patients. TPN-derived nitrogen intake was similar in both study groups. Nitrogen balances in the BCAA group (n = 49) were not different from those in the standard group (n = 52). Plasma total protein levels increased significantly in the standard group resulting in a significant difference between study groups on day 7. Pre-albumin levels increased significantly in the BCAA group and in the standard group. The number of neutrophils (rods) was significantly lower in the standard group compared to the BCAA group on day 7. Lymphocytes increased significantly in the standard group as did the number of platelets, resulting in a significant difference between study groups on day 7. We conclude that BCAA enrichment of standard TPN solutions does not result in more efficient nitrogen metabolism in septic or traumatized patients. PMID- 1899736 TI - George W. Holmes Lecture. Whose turf is imaging? Independent practice, academics and research. PMID- 1899737 TI - Breast sonography. AB - Sonographic equipment for breast imaging has continued to improve, and the role of breast sonography has evolved to that of an indispensable adjunct to mammography. Breast sonography is not useful for screening for breast cancer in any age group. Its main use is for the differentiation of cystic vs solid palpable and mammographically visible masses. If strict sonographic criteria are used for a simple cyst, the diagnostic accuracy approaches 100%. Sonographic diagnosis of a simple cyst precludes the need for further workup, including aspiration, biopsy, or followup. This article emphasizes the technical aspects of breast sonography, especially those factors that alter the diagnostic information on the images. These factors can be especially problematic in differentiating cysts and solid masses, the most common diagnostic use of breast sonography. Selection of equipment depends largely on the requirements of a specific practice. Optimally, the sonographic equipment is located close to where mammography is performed, and the sonographic and mammographic findings are interpreted together. PMID- 1899738 TI - Gadopentetate dimeglumine-enhanced MR imaging of the musculoskeletal system. AB - Contrast-enhanced MR imaging with gadopentetate dimeglumine has been used in the evaluation of musculoskeletal disorders only in recent years, and for the most part it is still under investigation. Review of the literature identified potential uses for this technique: (1) in the spine, for differentiation between scar tissue and recurrent disk herniation and for evaluation of epidural tumors; (2) in musculoskeletal tumors, for differentiation between tumor necrosis and peritumoral edema and for characterization and evaluation of tumors before and after treatment; (3) in the joints for delineation of cartilage and tendon tears, with intraarticular injection, and for differentiation between pannus and joint effusion, with IV injection; and (4) for delineation of infectious processes. Further studies are needed to confirm most of these potential indications. It is unlikely that gadopentetate dimeglumine-enhanced MR imaging will become a routine part of musculoskeletal MR imaging, and its use will be reserved for specific circumstances. PMID- 1899740 TI - Percutaneous removal of transvenous pacing lead perforating the heart, pericardium, and pleura. PMID- 1899739 TI - Detection of bullous lung disease: conventional radiography vs digital storage phosphor radiography. AB - The detection of fine linear contours and altered aeration are requirements for the radiologic diagnosis of bullous lung disease and are severe measures of the spatial and contrast resolution of chest imaging systems. We compared plain film radiography with five postprocessing algorithms of storage phosphor digital radiography (2144 x 1744 x 10 bit matrix with 0.2-mm pixel size) in the detection of CT-proved bullous lung disease (35 patients and 25 normal control subjects). Receiver-operating-characteristic analysis of 2160 observations by six interpreters was done to evaluate the observers' performance. By analysis of variance (p less than .05), we found that the default digital algorithm and the three edge-enhancing algorithms of high and medium frequencies performed less well than plain films did, but the differences fell short of statistical significance. Gray-scale reversal was the only digital algorithm that performed significantly less well than plain films did. We conclude that any differences between digital algorithms and plain films in the detection of bullous lung disease were too small to be detected in this study. Any difference between the two methods in providing clinically important, diagnostic information is likely to be insignificant. PMID- 1899741 TI - Candidal splenic abscesses. PMID- 1899742 TI - Intraabdominal Mycobacterium tuberculosis vs Mycobacterium avium-intracellulare infections in patients with AIDS: distinction based on CT findings. AB - Abdominal CT scans of 71 patients with AIDS who had proved disseminated infection due to Mycobacterium tuberculosis (27 patients) or Mycobacterium avium intracellulare (44 patients) were reviewed retrospectively to identify radiologic features that can be used to distinguish the two infections. CT findings in patients with disseminated M. tuberculosis included focal lesions in the liver (11%), spleen (30%), kidneys (19%), pancreas (7%), and gastrointestinal tract (15%) and lymph nodes with central or diffuse low attenuation (93%). CT findings in patients with disseminated M. avium-intracellulare included marked hepatomegaly (20%); marked splenomegaly (14%); focal lesions in the liver (9%), spleen (7%), and kidneys (2%); diffuse jejunal wall thickening (18%); lymph nodes with central low attenuation (14%); and enlarged lymph nodes exclusively of homogeneous soft-tissue density (55%). The presence of focal visceral lesions and low-attenuation lymph nodes suggests disseminated M. tuberculosis, whereas marked hepatic and splenic enlargement, diffuse jejunal wall thickening, and enlarged soft-tissue-density lymph nodes suggest disseminated M. avium-intracellulare. Recognition of these CT features can lead to a tentative diagnosis so that appropriate therapy can be instituted before the results of mycobacterial cultures become available. PMID- 1899743 TI - Gallstone fragmentation during biliary lithotripsy: effect of stone composition and structure. AB - In vitro lithotripsy with the Siemens Lithostar was conducted on 36 radiolucent or minimally calcified gallstones housed in an anthropomorphic phantom. The ease and pattern of fragmentation were correlated with global composition for the entire stone, regional or microcomposition (determined by Fourier-transform infrared spectroscopy), and microstructure (determined by scanning electron microscopy). Stones made up of more than 62% cholesterol required 50% more shock waves to pulverize all fragments to 0.3 cm or less than did stones of less than 62% cholesterol (p less than .01). An inverse relationship was found between the number of shock waves needed for fragmentation and the cholesterol content (r = .77). Although a broad range of fragmentation responses occurred, little variation was seen in the ease of fragmentation within stone families. The majority of stones fractured along radially oriented cholesterol plates, but one third of stones treated showed initial chipping or flaking at the periphery before radial fracture. This type of peripheral erosion most often occurred in stones with peripheral pigment rims. These stones required more shock waves and lagged in pulverization compared with more homogeneous cholesterol stones. The efficiency of fragmentation during biliary lithotripsy correlates with the stones' global cholesterol content. A stone's architecture, as reflected by its regional composition and microstructure, partially predicts the mechanism of fragmentation. These in vitro data may be useful in further refining criteria for selecting patients and understanding the fragmentation process. PMID- 1899744 TI - Natural history of acquired renal cystic disease in dialysis patients: a prospective longitudinal CT study. AB - Patients with end-stage kidney disease, particularly those treated with dialysis, develop proliferative processes in their native kidneys that result in the formation of multiple acquired renal cysts, renal adenomas, and carcinomas. Data about these abnormalities have been acquired mainly from retrospective studies. We undertook a longitudinal prospective study in which the native kidneys of 30 dialysis patients were surveyed by serial CT during a 7-year period to study the natural history of acquired renal cystic disease and the frequency of associated complications. Acquired cysts were seen in 87% of patients at the end of the study compared with 57% at the study's onset, and a significant increase was seen in mean renal volume with time. Five patients (17%) developed large hemorrhagic renal cysts and four (13%) developed large perinephric hematomas. Renal cell carcinomas developed in two patients (7%) without renal symptoms. One carcinoma invaded the renal capsule, but did not cause metastases. The other carcinoma was widely metastatic. Our findings are consistent with those of earlier studies documenting an increased prevalence of renal cell carcinoma in dialysis patients as compared with the general population. However, our conclusions are limited because the study sample is small and no control population was studied. We conclude that acquired renal cystic disease in dialysis patients is a progressive disorder often associated with cyst hemorrhage. Dialysis patients may also have an increased prevalence of renal cell carcinoma. PMID- 1899745 TI - Arteriovenous fistulas complicating biopsy of renal allografts: treatment of bleeding with superselective embolization. AB - The use of superselective embolization was assessed as a treatment for bleeding from postbiopsy arteriovenous fistulas (AVFs) in renal transplants. AVFs commonly occur after biopsy procedures in renal transplants, but severe bleeding is rare. Transcatheter embolization can be used to control bleeding, but unless it is sufficiently selective, the procedure results in loss of significant amounts of renal parenchyma. During a 4-year period, embolization procedures were attempted in seven patients 30-65 years old. All had AVFs shown on arteriography. Five patients underwent embolization; occlusion occurred only in the branch supplying the AVF. In one patient with three large AVFs, two were found to have occluded the day after embolization was attempted. In another, an AVF occluded when superselective catheter position was achieved but before embolization. Catheter manipulation in these cases may have precipitated occlusion. In five cases, coaxial embolization techniques were used. Embolization materials consisted of coils in three cases: 0.038 in. (0.97 mm) in one case, 0.025 in. (0.64 mm) in one case, 0.018 in. (0.46 mm) in one case; 0.038 in. (0.97 mm) coils and gelatin foam particles in one case; and localized contrast extravasation in one case. Serum creatinine level was measured before and after embolization in all patients, and radionuclide studies were undertaken in three cases. In all patients, bleeding was effectively controlled. None of the patients showed an increase in serum creatinine level after embolization, and in four, significant improvement was seen. Nuclear medicine studies showed no loss of renal function and a dramatic improvement in one patient. No complications due to the procedure were seen. Our experience suggests that superselective embolization with coaxial catheter techniques is an effective method of treating bleeding from postbiopsy AVFs in renal transplants with minimal loss of renal parenchyma. PMID- 1899746 TI - Carcinoma of the prostate: MR images obtained with body coils do not accurately reflect tumor volume. AB - MR imaging with a body coil is unreliable in directly demonstrating tumor spread through the prostatic capsule. However, the likelihood of extracapsular spread of prostatic cancer rises with increasing tumor volume. The aim of our study was to assess the accuracy of MR with a body coil in diagnosing capsular penetration indirectly via an estimation of prostatic tumor volumes. Twenty-six patients with proved prostatic cancer that was clinically confined to the gland underwent MR imaging before radical prostatectomy and whole-mount pathologic sectioning of the specimen. Twenty of 31 lesions prospectively outlined on the MR images corresponded to cancers outlined on the pathology slides, and tumor volumes were calculated by using a voxel summation technique. On MR, tumor volume was underestimated in 11 of 20 cases and overestimated in nine of 20 cases. Only two of 20 size estimates based on MR findings were within 10% of actual tumor volume. Overlap in MR tumor volumes was significant between lesions with and without capsular penetration at microscopy. Factors contributing to inaccuracies in measurements of tumor volume on MR images included the variable histologic make up of the tumors. Our results show that, although knowledge of the size of a prostatic lesion is important in predicting the behavior of the tumor, MR imaging with a body coil is not reliable for accurate estimation of tumor volume. PMID- 1899747 TI - MR imaging in sclerosing mesenteritis. PMID- 1899748 TI - Retroperitoneal sarcoidosis. PMID- 1899749 TI - CT appearance of the pelvis after cesarean section. AB - Myometrial defects at the incision site after cesarean section may appear bizarre on CT scans, especially in the case of low transverse incisions, but may not indicate clinically significant dehiscence. These CT findings should be regarded as common in the patient without complications after cesarean section, so that unnecessary surgical intervention and additional treatment can be avoided. PMID- 1899750 TI - CT pelvimetry: the foveae are not an accurate landmark for the level of the ischial spines. AB - The most important distance measured during CT pelvimetry is the interspinous diameter of the pelvis as seen on axial scans, because most cases of obstructed labor occur at the level of the ischial spines. As the spines are difficult to identify on the anteroposterior digital scout radiograph, the fovea of the femoral head has been used as a landmark to determine the level of the appropriate axial slice. We assessed the accuracy of this landmark on CT scans in 23 women undergoing CT pelvimetry and in 20 nonpregnant women having pelvic CT scans. In each case the relationship between the level of the foveae and the level of the ischial spines was determined. True interspinous distances were measured and compared with the apparent interspinous distances at the level of the foveae. In none of the women were the ischial spines above the foveae. In 15 (65%) of 23 pregnant women and in seven (35%) of 20 nonpregnant women, the ischial spines were below the foveae. An incorrect scanning level led to an overestimation of interspinous distance by an average of 1.0 cm. We conclude that for CT pelvimetry, the fovea as seen on the anteroposterior digital radiograph is an inaccurate landmark for the level of the ischial spines. PMID- 1899751 TI - Automated percutaneous lumbar diskectomy. AB - The use of automated percutaneous lumbar diskectomy for the treatment of herniated lumbar disks is increasing. More than 3000 physicians have been trained to perform the procedure, and over 40,000 cases have been completed worldwide. This review describes the development of automated percutaneous lumbar diskectomy, the selection of appropriate patients, how the technique is performed, and its efficacy relative to other methods of treatment. PMID- 1899752 TI - MR imaging in fibromatosis: results in 26 patients with pathologic correlation. AB - Fibromatoses are a diverse group of soft-tissue lesions that have been inconsistently categorized and treated. The purpose of our study was to establish the range of appearances of fibromatoses on MR images and perform a pathologic correlation to explain the variable signal-intensity patterns. During a 3-year period, 26 patients with deep fibromatoses were examined with MR. The MR images were evaluated for signal-intensity characteristics, and findings were correlated retrospectively with the pathologic diagnoses. The results showed that the MR appearance of fibromatoses is similar to that of other soft-tissue lesions, and the signal intensities vary greatly from lesion to lesion and within lesions themselves. The fibromatoses were either hyperintense, isointense, hypointense, or of mixed signal intensity relative to adjacent skeletal muscle. The hypointense areas appear to be zones of hypocellularity and dense collagen deposition. Microscopically all of the lesions invaded adjacent structures, but the MR appearances of the margins varied and were judged to be well demarcated (n = 14), intermediate (n = 5), or poorly demarcated (n = 6). Our experience shows that fibromatoses have a variable MR appearance no different from that of other soft-tissue lesions, and this variability reflects the composition and cellularity of the lesions. PMID- 1899753 TI - CT appearance of angiosarcoma associated with chronic lymphedema. PMID- 1899755 TI - Sonography of the fetal heart: findings on the four-chamber view. AB - The normal and pathologic sonographic appearances of the fetal heart on four chamber views are reviewed. Performed correctly, the four-chamber view is the best method of examining the complex cardiac anatomy of the small fetal heart and of detecting major congenital heart disease. PMID- 1899754 TI - Aspiration of the hip in patients treated with Girdlestone arthroplasty. PMID- 1899756 TI - John Sloan's "X-rays". PMID- 1899757 TI - Sonographic diagnosis of the amniotic band syndrome. PMID- 1899758 TI - CT amniography: value in detecting a monoamniotic pair in a triplet pregnancy. PMID- 1899759 TI - Deferoxamine-induced bone dysplasia in patients with thalassemia major. AB - Metaphyseal irregularity and abnormal vertebral bodies resembling a bone dysplasia were seen in two of five children with thalassemia major who were begun on a regimen of hypertransfusion and chelation with deferoxamine before the age of 3 years. Similar changes were not seen in 22 other children in whom chelation was started after the age of 3. Whether the dysplastic bone growth was related to drug dose or age of onset of chelation could not be determined, as deferoxamine dosages differed in the two groups. Findings on radiographs included flattening of the thoracic and lumbar vertebral bodies, circumferential metaphyseal osseous defects, sharp zones of provisional calcification, and widened growth plates. Healing was noted in one of the patients after the dose of deferoxamine was decreased. Zinc levels in both affected patients did not differ from those in the 25 other chelated patients. PMID- 1899760 TI - Aortic thrombosis after umbilical artery catheterization in neonates: prevalence of complications on long-term follow-up. AB - We previously reported the early natural history of aortic thrombosis occurring after umbilical artery catheterization in 21 neonates. Ten of those neonates were reevaluated at 36-42 months of age for evidence of hypertension, renal abnormalities, and leg-growth disturbances. They were compared with an age matched control group of seven infants. Blood pressures were greater than the 95th percentile in three infants and between the 50th and the 95th percentile in six of the 10 infants. Height was less than the fifth percentile for age in four infants with aortic thrombosis. One child had a 1.0-cm discrepancy in leg-length measurements, and seven of nine patients exhibited a 0.5-2.0 cm discrepancy between legs in either thigh or calf circumference. Sonography showed no evidence of residual clot in the aorta or renal vessels. Doppler flow was normal in all cases. Despite resolution of neonatal aortic thrombosis, complications resulting in renovascular hypertension (three of 10 patients) and leg-growth abnormalities (eight of nine) can occur. Hypertension (one of seven) and leg-growth discrepancy (four of seven) were less frequent in the 3-year follow-up of the seven matched control infants. We suggest that infants with known aortic thrombosis receive long-term follow-up to detect these potential problems. PMID- 1899761 TI - Posterior fossa intracranial hemorrhage in infants treated with extracorporeal membrane oxygenation: sonographic findings. AB - Posterior fossa hemorrhage was documented by autopsy in five infants who had been treated with extracorporeal membrane oxygenation over a 5-year-period. In all five cases, the diagnosis was made prospectively by cranial sonography. Sonographic findings were compared with those in a control group of 15 infants with normal posterior fossae at autopsy. The following sonographic abnormalities were exhibited in neonates with posterior fossae hemorrhage: loss of definition of the cerebellum and fourth ventricle on midline sagittal images, heterogeneous cerebellar parenchyma, focal hypoechoic lesions, ventricular dilatation, and tentorial abnormalities. Bright foci inferior to the third ventricle were seen in four neonates in the normal control group. These foci measured 5-10 mm in diameter. One cranial sonogram was falsely interpreted as showing a posterior fossa hemorrhage because of prominent echoes in the interpeduncular cistern. Infants treated with extracorporeal membrane oxygenation are at risk for developing posterior fossa hemorrhage. Awareness of sonographic signs and potential pitfalls in the interpretation of posterior fossa hemorrhage is important for early and accurate recognition of these unusual and sometimes treatable hemorrhages. PMID- 1899762 TI - Schmid-like metaphyseal chondrodysplasia simulating child abuse. PMID- 1899763 TI - MR anatomy and pathology of the hypothalamus. AB - The hypothalamus, the ventral-most portion of the diencephalon, surrounds the anterior inferior portion of the third ventricle (Fig. 1). It functions primarily as an integrative mechanism for various autonomic and neuroendocrine activities including temperature regulation, water balance, behavior, and appetite. This pictorial essay illustrates the value of MR in depicting the normal anatomy and abnormalities of the hypothalamic region. PMID- 1899764 TI - Fate of manuscripts rejected for publication in the AJR. AB - The fate of rejected manuscripts that were originally submitted to the American Journal of Roentgenology (AJR) during the first 5 months of 1986 was investigated to learn whether, when, and where they had been published. AJR, a peer-reviewed journal of diagnostic radiology with a circulation of over 21,000, annually publishes about 500 papers and receives over 11,500 citations. MEDLINE searches conducted 45 to 54 months after the dates of rejection by AJR located 162 (64%) published papers out of a consecutive series of 254 manuscripts rejected by AJR, including 69% of the rejected major papers and 62% of the rejected case reports. The papers had been published in 30 different radiologic and 27 different nonradiologic journals. Most of these journals published fewer papers, had smaller circulations, and had lower impact factors (a ratio of citations received to papers published) than AJR does. The mean time lapse between rejection by AJR and publication in other journals was 15 months. The delay in publication was greater for papers published in nonradiologic and foreign journals than for papers published in radiologic and American journals. The results of this study indicate that rejection of a manuscript by a peer-reviewed journal such as AJR delays but by no means precludes publication. At least 82% of the major papers and 70% of the case reports that are submitted to AJR are eventually published, either in AJR or elsewhere. Because a scientific paper represents not only many hours of writing and manuscript preparation but also a great investment of research time and resources, authors are reluctant to abandon rejected manuscripts. In the majority of cases, submission to other journals gains acceptance and publication. PMID- 1899765 TI - Prevention of claustrophobia induced by MR imaging: use of alprazolam. PMID- 1899766 TI - Prevention of vomiting induced by i.v. contrast media. PMID- 1899767 TI - Stereotactic breast biopsy with a 20-gauge needle. PMID- 1899768 TI - Hepatic calcifications presumably due to congenital syphilis. PMID- 1899769 TI - Differentiation of child abuse from osteogenesis imperfecta. PMID- 1899771 TI - Oblique plain radiographs in the diagnosis of ureteral calculi. PMID- 1899770 TI - Doppler assessment of fetal circulation in a case of fetal death. PMID- 1899772 TI - Radiology of the cervical spine in trauma patients. PMID- 1899773 TI - Biopsy gun and sheath for CT-guided percutaneous biopsies. PMID- 1899774 TI - Membranous stenosis of the inferior vena cava: prevention of placement of a Kimray-Greenfield filter via the jugular vein. PMID- 1899775 TI - Modified delivery catheter for Wallstent treatment of renal artery stenosis. PMID- 1899776 TI - Dynamic QRS-complex and ST-segment monitoring in acute myocardial infarction during recombinant tissue-type plasminogen activator therapy. The TEAHAT Study Group. AB - Changes of the QRS complex are the electrocardiographic expression of irreversible injury of the myocardium. In humans, the process of infarction occurs over several hours. A more rapid development of QRS changes has been reported in patients treated with thrombolytic agents. Patients with strongly suspected acute myocardial infarction (AMI) included in a placebo-controlled trial of 100 mg of recombinant tissue-type plasminogen activator (rt-PA) were monitored for 24 hours with continuous, on-line vectorcardiography. The magnitude of the QRS vector changes correlated with infarct size estimated by the maximal value of lactate dehydrogenase-1 (r = 0.69, p less than 0.001) as well as with left ventricular ejection fraction 30 days after randomization (r = 0.49, p less than 0.001). Treatment with intravenous rt-PA limited total QRS vector change but the QRS vector changes observed occurred more rapidly and reached a plateau 131 minutes earlier in patients treated with rt-PA than in those receiving placebo (p less than 0.01). A certain pattern of highly variable ST vector magnitude was identified and was associated with higher maximal lactate dehydrogenase-1 values (23 +/- 13 vs 14 +/- 10 mu kat/liter, p less than 0.001) and a tendency to higher 1-year mortality (24 vs 9%, p = 0.08) than in patients without this pattern. In patients with this pattern, rt-PA did not affect maximal lactate dehydrogenase-1, time to maximal creatine kinase and final magnitude of QRS vector change. PMID- 1899777 TI - Impetigo. PMID- 1899778 TI - Direct and indirect effects in vaccine efficacy and effectiveness. AB - In 1915, Greenwood and Yule noted that for valid vaccine efficacy studies, exposure to infection in the vaccinated and the unvaccinated must be equal (Proc R Soc Med 1915;8(part 2):113-94). The direct effect of a vaccine, however, needs to be defined by the protection it confers given a specific amount of exposure to infection, not just a comparable exposure. In this paper, two classes of parameters are distinguished along lines differing from the conventional distinction between efficacy and effectiveness. Efficacy parameters attempt to control for exposure to infection and represent direct effects on individuals. Direct effectiveness parameters represent a mixture of direct effects on individuals and indirect effects in the population. PMID- 1899779 TI - The epidemiology of listeriosis in the United States--1986. Listeriosis Study Group. AB - To determine the morbidity and mortality due to listeriosis in the United States, the authors undertook an active surveillance project in 1986 to identify all cases in which Listeria monocytogenes was isolated from cultures of ordinarily sterile sites in a population of 34 million persons. The authors estimated that at least 1,700 cases of listeriosis and 450 deaths occurred in the United States in 1986; 27% of these cases occurred in pregnant women, with 22% of perinatal cases resulting in stillbirths or neonatal deaths. The risk of listeriosis in adults (0.5 per 100,000 population) was similar in all regions studied; the incidence of perinatal listeriosis was three times higher in Los Angeles County, California, than in the other areas (24.3/100,000 live births vs. 7.8/100,000 live births). Geographic variation may have resulted from underdiagnosis of perinatal listeriosis in five of the study areas. Multilocus electrophoretic enzyme typing was useful for elucidating the molecular epidemiology of L. monocytogenes; perinatal listeriosis was significantly associated with one group of related strains. Multilocus electrophoretic enzyme typing also identified three clusters representing possible common-source outbreaks. These findings document the substantial morbidity due to listeriosis in the United States; to the extent that sporadic listeriosis is foodborne, this morbidity could be reduced by appropriate preventive measures, particularly in persons known to be at increased risk of infection. PMID- 1899780 TI - Properties of adenotin reconstituted into phospholipid vesicles. AB - Adenotin is a low affinity adenosine binding protein that has amino terminal homology with mammalian and avian stress proteins. Human placental adenotin was solubilized and reconstituted into phospholipid vesicles with an overall yield of 30%. The properties of adenotin in vesicles were similar to the native membranes as follows: association has a Kobs of 0.61 +/- 0.03 minute-1; equilibrium is reached in approximately 15 minutes; and the first order dissociation constant is 5.0 +/- 0.3 minute-1. Displacement analysis reveals an agonist potency order and Ki values as follows: N-ethylcarboxamidoadenosine, 0.35 microM; 2 chloroadenosine, 1.5 microM; R-phenylisopropyladenosine, greater than 1000 microM. The addition of 100 microM 5'-guanylylimidodiphosphate did not decrease binding of 5'-N-ethylcarboxamidoadenosine (NECA) at 37 degrees C or 4 degrees C but did decrease the IC50 for PC12 and JAR cell membrane agonist binding from 9.9 to 3.3 microM and increase the binding to 150-211% of the control value at 37 degrees C. The latter studies at 37 degrees C showed high variability. Using binding sites reconstituted into vesicles and gel filtration chromatography and agonist related guanine nucleotide release, the authors investigated whether these changes were related to an interaction between adenotin and a guanine nucleotide regulatory protein. No evidence for such an interaction was found. These data suggest that adenotin retains its binding properties when reconstituted into phospholipid vesicles. The function of this low affinity adenosine binding site remains to be discovered. However, the reconstitution of adenotin into phospholipid vesicles provides a method to study its function. PMID- 1899781 TI - Coincidental hemochromatosis and viral hepatitis. AB - A 35-year-old woman presented with liver failure, hepatic iron overload, and secondary amenorrhea due to hypogonadotropic hypogonadism. She had chronic inflammatory hepatitis which was considered to be due to post-transfusional viral hepatitis. Her hepatic iron overload was considered to be due to hemochromatosis. Her premature menopause was thought to be due to the severity of her liver disease, but her iron overload also could have contributed to gonadotrophin deficiency. She underwent liver transplantation and 5 months later, she experienced return of menstrual function. The distinction between hepatitis as a cause of iron loading, hemochromatosis as a cause of hepatic inflammation, the small influence of alcohol on increased iron stores, and other features of her history, physical examination, and laboratory evaluation are discussed. PMID- 1899782 TI - Experimental hyperthermia: protective effect of oxygen carrying fluorocarbon and crystalloids intraperitoneally. AB - The treatment of hyperthermia produced by passive warming was studied in anesthetized rats weighing 250-300 grams. In the first set of seven experiments, the authors found that venous blood oxygen fell as core temperature rose. Intraperitoneal injection of 20 ml of the oxygen carrying fluorocarbon (perfluorotributylamine, FC-43) emulsion in three of the animals shifted the curve to the right improving venous oxygen content (p less than 0.1). In the second series of experiments, a catheter was placed in the carotid artery. This catheter was attached to a pressure transducer for continuous recording of blood pressure and heart rate. Periodic blood samples were removed for measurement of blood gases, pH, and lactate. Four of the animals received 20 ml of isotonic saline, three received 20 ml of FC-43 emulsion both given intraperitoneally, and four served as controls. In the control group, there was an increase in systolic blood pressure and heart rate which peaked at a colon temperature of 42 degrees C, followed by cardiovascular collapse and death around 43 degrees C. Arterial PO2 (corrected for temperature) remained relatively constant up to 42 degrees C, and then fell. The arterial PCO2 rose sharply when the core temperature exceeded 43 degrees C. Arterial lactate content began to increase at 42 degrees C and above 43 degrees C was 2.5 fold elevated. Isotonic saline provided circulatory support but did not change the hypoxia or mixed acidosis from CO2 and lactate above 43 degrees C. FC-43 emulsion decreased hypoxia and improved circulatory performance but was associated with a mild respiratory alkalosis as arterial PCO2 fell.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1899783 TI - A simplified human whole blood assay for measurement of dust mite-specific gamma interferon production in vitro. AB - A simplified microassay for the measurement of spontaneous and dust mite antigen induced gamma interferon (IFN) production in vitro using unseparated human blood has been developed. Gamma IFN in 72-hour culture supernatants was measured using a solid phase radioimmunoassay. Maximum production in allergic patients occurred between 25 and 50 micrograms/mL of mite antigen. Both spontaneous and antigen stimulated levels were highest in the group of mite-allergic patients compared with nonallergic patients or normal controls. Gamma IFN production was lower in a group of mite-allergic patients on immunotherapy compared with the nonimmunotherapy group. Treatment with even small doses of oral corticosteroids completely obliterated both spontaneous and stimulated gamma IFN production. These results indicate that this whole blood assay coupled with a lymphokine radioimmunoassay is a convenient, rapid, and sensitive method for measuring cell mediated immunity to allergens and responses to IT or drug treatment that can be easily adapted to testing large number of patients. PMID- 1899784 TI - Update on the physical-chemical compatibility of cromolyn sodium nebulizer solution: bronchodilator inhalant solution admixtures. AB - Cromolyn sodium nebulizer solution, 1% (wt/vol), is physically and chemically compatible (stable) for at least 90 minutes when mixed in vitro with a new formulation (metabisulfite-free) of metaproterenol sulfate solution, an inhalant solution of albuterol sulfate or an atropine sulfate inhalant solution. Similarly, cromolyn sodium does not adversely affect the stability of the individual bronchodilator drugs in the admixtures. Since cromolyn sodium is compatible in admixtures with these bronchodilator drugs, adding these agents to cromolyn sodium nebulizer solution should have no negative influence on the effectively administered dose of either active ingredient. PMID- 1899785 TI - Severe hypophosphataemia during binge eating in anorexia nervosa. AB - A patient presented with severe hypophosphataemia that had been precipitated during binge eating. It was corrected by restricting the binges, and by hyperalimentation through a duodenal tube together with intravenous supplementation with sodium phosphate for a short period. Phosphate concentrations should be monitored in patients with severe anorexia complicated by bulimic episodes. PMID- 1899786 TI - Nasogastric feeding at home: acceptability and safety. AB - A questionnaire was administered to 70 families with experience of home enteral nutrition. All but one patient received at least some of their feeding overnight. During 11,041 patient days of home enteral nutrition, no serious complications were seen. Sleep disturbance was common, however, and affected 59 parents and 35 children. A nocturnal cough or 'chestiness' were noted in 10 children suggesting occult gastro-oesophageal reflux. Enteral feeding disposables were not prescribable by general practitioners, and funding for the equipment was inadequate in the hospital and community. The mean time to arrange funding for equipment was eight months (range two weeks to two years). Parental views on home enteral nutrition were positive and none felt that its disadvantages outweighed the benefits. Altogether 35 children were described as being more happy and active. Given adequate preparation and continued support at home, parents can manage home enteral nutrition safely and effectively. PMID- 1899787 TI - Cognitive deficits in children treated for leukaemia. PMID- 1899788 TI - Pleuropulmonary complications of fine bore naso-enteric feeding tubes. AB - Fine bore naso-enteric feeding tubes are commonly used for enteral alimentation. Although regarded as generally safe, complications associated with their use occur. Case reports presented here highlight the potential hazards of these tubes. Pleuropulmonary complications are reviewed and guidelines suggested for the safe insertion of such tubes. PMID- 1899789 TI - The influence of branched chain amino acids on colonic atrophy and anastomotic strength in the rat. AB - Conventional solutions of parenteral nutrients fail to reverse the colonic atrophy caused by starvation. This may be due to the absence from these solutions of the amino acid glutamine--a fuel for rapidly dividing cells such as colonocytes and fibroblasts. Although glutamine is unstable in solution, the infusion of branched chain amino acids (BCAA) increases the rate of synthesis and release of glutamine from skeletal muscle. We evaluated the hypothesis that the infusion of BCAA into undernourished rats would reduce the extent of mucosal atrophy and enhance the healing of anastomoses in the colon. Undernourished rats were randomized to receive 6 days of either a normal diet (Chow), conventional parenteral nutrition (CPN), or CPN supplemented with 1.8% BCAA (BCAA). The BCAA group had a higher plasma glutamine concentration than the Chow group (P less than 0.05). Compared with the CPN group, the BCAA group had the greater colonic mucosal weight (P less than 0.05) and colonic mucosal protein content (P less than 0.05), but there were no significant differences between groups in the bursting wall tension of the colon or the hydroxyproline content of the anastomoses. Although the infusion of BCAA has a beneficial effect on colonic atrophy, this did not result in the more secure healing of colonic anastomoses in this experimental model. PMID- 1899790 TI - Suppressive effect of biscoclaurine alkaloids on agonist-induced activation of phospholipase A2 in rabbit platelets. AB - The effect of biscoclaurine (bisbenzylisoquinoline) alkaloids on phospholipase A2 and C activation in signal transduction system of rabbit platelet was studied. Isotetrandrine, cepharanthine and berbamine inhibited the aggregation induced by collagen but not by other stimuli such as thrombin and arachidonic acid, while tetrandrine equally inhibited the aggregation by any of these agonists. All these four alkaloids suppressed arachidonic acid liberation in response to collagen or thrombin, but not diacylglycerol formation and increase in cytoplasmic Ca2+ concentration in response to thrombin or arachidonic acid. In saponin permeabilized platelets, they also suppressed arachidonic acid liberation induced by an addition of both GTP gamma S and Ca2+, whereas the liberation induced by an addition of Ca2+ alone was not prevented by them. These data suggest that isotetrandrine, cepharanthine and berbamine have a rather specific potency to suppress the phospholipase A2 activation by a mechanism other than direct inhibition of the enzyme or interference with the ligand-receptor interaction. They seem, at least in part, to exert the effect on the GTP-binding protein phospholipase A2 complex in the platelet signal transduction system. In contrast, tetrandrine appears to inhibit a step following an increase in cytosolic free Ca2+ concentration in the agonist-induced signal transduction system, in addition to suppressing the phospholipase A2 activation. PMID- 1899792 TI - Gonococcal arthritis caused by penicillinase-producing strains of Neisseria gonorrhoeae. PMID- 1899791 TI - Semicarbazide-sensitive amine oxidase activity (SSAO) of rat epididymal white adipose tissue. AB - An amine oxidase activity distinguishable from MAO, which is inhibited by carbonyl reagents is present in rat epididymal WAT. This enzyme, referred to as semicarbazide-sensitive amine oxidase (SSAO), appears concentrated in adipose cells. Close homologies between WAT SSAO and the circulating plasma BAO are discussed. PMID- 1899793 TI - Plasma levels of tissue-type plasminogen activator and von Willebrand factor in patients with Raynaud's phenomenon. PMID- 1899794 TI - Nutritional status and dietary intake of patients with pressure ulcers: review of research literature 1943 to 1989. AB - This literature review summarizes research on nutrition and pressure ulcers from 1943 to 1989. The focus is on dietary intake of protein and calories, body weight, serum total protein, albumin, hemoglobin, total lymphocyte count, iron, zinc, and vitamin C. The literature clearly demonstrates that patients with pressure ulcers are malnourished. PMID- 1899795 TI - Galactosyltransferase activity is restricted to the plasma membranes of equine and bovine sperm. AB - beta 1, 4-Galactosyltransferase (GalTase) is localized to the plasma membrane of mouse sperm, in which it mediates the binding of sperm to glycoconjugate residues in the egg zona pellucida. In this study, the presence of subcellular distribution of sperm GalTase were determined in two other mammalian species that yield sufficient sperm for subcellular fractionation. Equine and bovine semen were collected, and the plasma membranes (PM), outer acrosomal membranes (OAM), and inner acrosomal membranes (IAM) were sequentially removed. The purities of the isolated membrane preparations were determined by transmission electron microscopy and found to be greater than or equal to 90%, 96%, and 98% for equine PM, OAM, and IAM, respectively, and greater than or equal to 80%, 94%, and 97% for bovine PM, OAM, and IAM, respectively. GalTase activity was assayed under optimal conditions in all membrane preparations and was preferentially localized to the isolated PM both in equine and in bovine spermatozoa. The selective localization of GalTase to the sperm PM in two other species suggest that it may serve as a generalized gamete receptor during initial sperm-egg binding in mammals. PMID- 1899796 TI - [A case with MELAS associated with epilepsia partialis continua]. AB - We report a 14-year-old boy with mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes (MELAS) who presented repeated episodes of abdominal pain and vomiting since the age of 8 years. In addition, he developed strokelike episodes with myoclonic seizures and transient hemiplegia on three occasions. At the age of 14-1/12-years, he also developed epilepsia partialis continua persisting for 10 days, which was associated with myoclonic seizures synchronized with spike discharges at the right central area. Laboratory examination disclosed increased levels of lactate and pyruvate in serum and CSF and low density areas in the bilateral temporal regions on CT scan. Muscle biopsy showed scattered ragged-red fibers. The enzyme activities (pyruvate dehydrogenase complex, pyruvate carboxylase, phosphoenol pyruvate carboxykinase, and cytochrome c oxidase) and the rates of decarboxylation of [3-14C]pyruvate in cultured skin fibroblasts were within normal ranges. PMID- 1899797 TI - Effect of oxyquinoline ointment on diaper dermatitis. AB - The effectiveness of oxyquinoline ointment for diaper dermatitis was tested in a randomized double-blind trial. Compared to a combined control treatment group using Desitin or A & D ointment, use of oxyquinoline ointment significantly improved rash. PMID- 1899798 TI - Effect of deficiencies in DNA repair on the toxicity of mitomycin C and porfiromycin to CHO cells under aerobic and hypoxic conditions. AB - A wild type Chinese hamster cell line (AA8) and three repair-deficient sublines of AA8 (EM9, UV4, and UV5) were used to study the nature of the cytotoxic lesions produced by the bioreductive alkylating agents mitomycin C and porfiromycin under aerobic and hypoxic conditions. The sensitivities of the repair-deficient sublines to the drugs varied markedly: EM9 was similar to AA8, whereas UV4 was exquisitely sensitive and UV5 was of intermediate sensitivity. Moreover, both the relative toxicities of the two drugs and the relative toxicities of each drug under aerobic and hypoxic conditions varied for the different cell lines. These data suggest that there are differences in the spectra of toxic lesions produced by mitomycin and porfiromycin and that there are differences in the lesions produced by these drugs under aerobic and hypoxic conditions. PMID- 1899799 TI - Taxonomy of the genus Listeria by using multilocus enzyme electrophoresis. AB - Seventy-three strains of the seven recognized Listeria species were studied by performing a multilocus enzyme electrophoresis analysis of 18 enzyme loci. The mean number of alleles per locus was 9.5 and all of the loci were polymorphic. A total of 56 electrophoretic types were distinguished. Cluster analysis of a matrix of the genetic distances between paired electrophoretic types revealed that there were six principal clusters at the species level (genetic distances between clusters greater than 0.8). Listeria monocytogenes, Listeria innocua, Listeria welshimeri, Listeria seeligeri, and Listeria ivanovii each corresponded to one of these clusters with no overlap. Our results are in agreement with those of previous DNA hybridization experiments (Rocourt et al., Curr. Microbiol. 7:383 388, 1982). Listeria grayi and Listeria murrayi electrophoretic types formed a unique cluster, thus reinforcing the suggestion of Wilkinson and Jones (J. Gen. Microbiol. 98:399-421, 1977) that these two species should be considered two biovars of a single species. PMID- 1899800 TI - Divalent cation-sensitive pores formed by natural and synthetic melittin and by Triton X-100. AB - Leakage of ions and low-molecular-weight metabolites from Lettre cells is induced by synthetic melittin, as effectively as by melittin isolated from bee venom; in each case leakage is inhibited by Ca2+, Zn2+ or H+. Inhibition of leakage by divalent cations is reversible in that Lettre cells incubated with melittin (or with Triton X-100) in the presence of inhibitory amounts of Zn2+, when freed of Zn2+ by EGTA or by centrifugation, begin to leak (in Zn2(+)-sensitive manner). Electrorotation of Lettre cells is altered by melittin, compatible with membrane permeabilization; melittin plus Zn2+ does not alter electrorotation until Zn2+ (and unbound melittin) are removed. Melittin or Triton X-100 added to calcein loaded liposomes induces leakage of calcein; divalent cations inhibit. Energy transfer between liposome-associated melittin and 2-, 7- or 12-(9 anthroyloxy)stearate (AS) is maximal with 12-AS; addition of Zn2+ has little effect. Circular dichroism spectra of melittin plus liposomes are unaffected by Zn2+. These results show that the formation of divalent cation-sensitive pores is not dependent on the presence of endogenous membrane proteins and that the action of divalent cations is not by displacement of melittin (or Triton) from the lipid bilayer. PMID- 1899801 TI - Beta-galactosidase fused to the hydrophobic domain of cytochrome b5 spontaneously associates with liposomes. AB - Since liver microsomal cytochrome b5 spontaneously associates with liposomes and membranes by means of its C-terminal hydrophobic domain (HP), chimeric proteins containing HP prepared by genetic fusion might also spontaneously associate with liposomes or cellular membranes. Synthetic DNA corresponding to the hydrophobic domain of cytochrome b5 was enzymatically fused in-frame to cloned DNA corresponding to the C-terminus of the Escherichia coli enzyme, beta galactosidase. This protein, LacZ:HP, synthesized in E. coli and purified from a crude E. coli membrane extract, was shown to spontaneously associated with liposomes, as does cytochrome b5. Association is rapid and stable in the presence of salt and high pH and the fusion protein behaves as an integral membrane protein. LacZ:HP can be readily and extensively purified from crude extracts by association with liposomes and this procedure may provide a convenient purification scheme for proteins not otherwise readily purified, for example polypeptides from cloned gene fragments to be used for antibody production. These hybrid proteins may represent a new potentially useful class of polypeptides capable of hydrophobic interactions with membranes. PMID- 1899802 TI - Plasma membrane-bound carbonic anhydrase activity in the regenerating rat liver. AB - Part of the carbonic anhydrase activity of hepatocytes has been reported to be located in the plasma membrane. This strategic location suggests a physiological role other than that located within the cell and probably related to the specific secretory function of these cells. Furthermore, after two-thirds hepatectomy an enzymatic retrodifferentiation has been reported. We reasoned that liver regeneration probably affects the carbonic anhydrase activity in different ways depending upon its location and hence presumably physiological role. We measured, therefore, carbonic anhydrase activity in a soluble fraction or in a plasma membrane-enriched fraction obtained from liver homogenate from rats undergoing hepatectomy (two-thirds) one, three or seven days before liver resection and homogenation. No changes in carbonic anhydrase activity were found as far as soluble fraction was concerned. However, the carbonic anhydrase activity in plasma membrane was reduced (by 55%) soon after hepatectomy, there after it increased, returning to near control value at seven days. Lactate dehydrogenase activities in soluble and plasma membrane fractions were not modified by the regenerative process. Neither was 5'-nucleotidase activity determined in plasma membrane affected by liver regeneration. In summary, these results indicate a higher sensitivity of plasma membrane carbonic anhydrase activity to the regenerative process than soluble carbonic anhydrase activity. This suggests a different control of the turnover of these isoenzymes during rat liver regeneration. The phenomenon is consistent with a different physiological role for these activities; i.e., one (plasma membrane-bound carbonic anhydrase activity) may be involved in specific functions of differentiated hepatocytes, and another (soluble carbonic anhydrase activity) may be involved in general functions shared by both differentiated and undifferentiated cells. PMID- 1899803 TI - Activation of human monocyte-derived macrophages by interferon gamma is accompanied by increase of poly(ADP-ribose) polymerase activity. AB - We have investigated poly(ADP-ribosyl)ation processes in human monocyte-derived macrophages and the effect of the activating cytokine, interferon gamma (IFN gamma) on these processes. IFN-gamma was shown to increase the activity of poly(ADP-ribose) polymerase in human macrophages. A 2-3-fold enhancement of poly(ADP-ribose) polymerase activity was observed after 3-4 h of incubation with IFN-gamma, whose effects were dose-dependent and maximal at 20-50 U/ml. Staining with anti-poly(ADP-ribose) antibodies and purification of ADP-ribosylated nuclear proteins by affinity chromatography over boronate agarose showed that enhancement of poly(ADP-ribose) polymerase activity by IFN-gamma was accompanied by accumulation of poly(ADP-ribose) polymers in nuclear proteins. The effects of IFN gamma on poly(ADP-ribose) polymerase activity were not due to an enhanced accumulation of the message for the enzyme, indicating that the activation of the enzyme activity was due to post-transcriptional modifications. IFN-gamma was shown to induce DNA strand breaks in human macrophages. This phenomenon followed the same time-course and was evident with the same doses of IFN-gamma that increased poly(ADP-ribose) polymerase activity. Since poly(ADP-ribose) polymerase is known to require DNA nicks for its activity, the capability of IFN-gamma to induce DNA strand breaks can explain its effects on poly(ADP-ribosyl)ation processes. PMID- 1899804 TI - Potentiation of arachidonic acid release by phorbol myristate acetate in platelets is not due to inhibition of arachidonic acid uptake or incorporation into phospholipids. AB - Activators of protein kinase C, such as tumor-promoting phorbol esters (e.g., phorbol myristate acetate), mezerein, (-)-indolactam V and 1-oleoyl 2-acetoyl glycerol, potentiate arachidonic acid release caused by elevation of intracellular Ca2+ with ionophores. This action of protein kinase C-activators required protein phosphorylation, and was attributed to enhanced hydrolysis of phospholipids by phospholipase A2 (Halenda, et al. (1989) Biochemistry 28, 7356 7363). Recently Fuse et al. ((1989) J. Biol. Chem 264, 3890-3895) reported that the apparent enhanced release of arachidonate was actually due to inhibition of the processes of re-uptake and re-esterification of released arachidonic acid. They attributed this to loss of arachidonyl-CoA synthetase and arachidonyl-CoA lysophosphatide acyltransferase activities, which were measured in membranes obtained from phorbol myristate acetate-treated platelets. In this paper, we show that phorbol myristate acetate, at concentrations that strongly potentiate arachidonic acid release, does not inhibit either arachidonic acid uptake into platelets or its incorporation into specific phospholipids. Furthermore, the fatty acid 8,11,14-eicosatrienoic acid, a competitive substrate for arachidonyl CoA synthetase, totally blocks arachidonic acid uptake into platelets, but, unlike phorbol myristate acetate, does not potentiate arachidonic acid release by Ca2+ ionophores. We conclude that the action of phorbol myristate acetate is to promote the process of arachidonic acid release by phospholipase A2. PMID- 1899805 TI - Reduction of mono(ADP-ribosyl)ation of 20 kDa protein with maturation in rat testis: involvement of guanine nucleotides. AB - When the homogenate prepared from immature rat testes was incubated with [32P]NAD, several proteins (90, 39 and 20 kDa) were ADP-ribosylated in the absence of bacterial toxins. This observation suggested the existence of an endogenous ADP-ribosyltransferase and substrates. The data that the digested product by phosphodiesterase of ADP-ribosylated 20 kDa protein was 5'-AMP suggested that 20 kDa protein was mono(ADP-ribosyl)ated. In addition, the mono(ADP-ribosyl)ation of 20 kDa protein was enhanced by guanine nucleotides such as GTP, GDP and GTP[gamma S], and decreased by the concentrations of 10 mM Mg2+. In contrast, the incorporation of ADP-ribose moiety from NAD to both 90 and 39 kDa proteins was not changed by guanine nucleotides. On the other hand, mono(ADP ribosyl)ation of 20 kDa protein was not observed in the homogenate prepared from other tissues of the same rats. Furthermore, we found that mono(ADP-ribosyl)ation of 20 kDa protein was decreased with the maturation of the rats and that an endogenous mono(ADP-ribosyl)transferase and 20 kDa protein were located in the nuclei. PMID- 1899806 TI - Requirement of heparin for arterial and venous thrombolysis with recombinant tissue-type plasminogen activator. AB - The effect of concomitant intravenous (IV) heparin (200 U/kg bolus, followed by 100 U/kg/h) on the efficacy of arterial and venous thrombolysis with IV recombinant tissue-type plasminogen activator (rt-PA; 0.5 mg/kg over 1 hour) was investigated in a combined femoral arterial and venous thrombosis model in the dog. The arterial model consisted of a high-grade stenosis, endothelial damage, and a thrombotic occlusion, and the venous model consisted of a 125I-fibrin labeled blood clot. After a dose-finding pilot study in four dogs, a randomized, prospective, and blind study was performed in 20 animals pretreated with 2.8 mg/kg IV acetyl salicylic acid (ASA). The combination of rt-PA and heparin (group I, n = 10) induced early (less than 30 minutes) arterial reperfusion in seven dogs, late (greater than 30 minutes) reflow in two dogs, and persistent occlusion in one dog. rt-PA alone (group II, n = 10) was associated with early reperfusion in one dog, late reflow in three dogs, and persistent occlusion in six dogs (P = .018). Reocclusion occurred in five of nine reperfused dogs of group I and in one of four reperfused dogs of group II (P = not significant). Venous clot lysis amounted to 81% +/- 4% (mean +/- SEM) for group I and to 49% +/- 7% for group II (P less than .001). Template bleeding times increased moderately, but significantly, in group I (from 2.2 +/- 0.2 minutes at baseline to 7.0 +/- 1.4 minutes at 30 minutes, P = .006), but only marginally in group II (from 2.2 +/- 0.2 minutes to 3.6 +/- 0.7 minutes, P = .09). No systemic fibrinogen depletion was observed. Thus, the concommitant use of heparin with rt-PA accelerates arterial reperfusion and enhances venous thrombolysis in dogs pretreated with ASA. These results, obtained in a randomized prospective study design, add to a growing body of experimental and clinical evidence, indicating that thrombolytic therapy with rt-PA requires concomitant adjunctive IV heparin for optimal efficacy, even in the face of treatment with ASA. PMID- 1899807 TI - Expression of the c-myc protein is down-regulated at the terminal stages during in vitro differentiation of B-type chronic lymphocytic leukemia cells. AB - The translocated c-myc oncogene in Burkitt's lymphoma (BL) and murine plasmacytoma (MPC) has been proposed to be expressed at a stage of differentiation at which the gene is normally silent, resulting in a continuous proliferation and an inhibited terminal differentiation. To determine whether c myc is differently expressed at the various stages of the differentiation pathway, we used B-type chronic lymphocytic leukemia (B-CLL) cells, representing resting B lymphocytes, inducible to proliferation and/or differentiation in vitro. The c-myc protein, and Ig lambda-light chain and PCA-1 antigen as markers of B-cell maturation, were analyzed in single, morphologically defined cells by immunocytochemical double-staining. The proliferation of individual cells was determined by 3H-thymidine incorporation and by analysis of Ki-67 antigen expression. The results show that the level of c-myc expression correlates to the stage of differentiation and to the proliferative activity. Uninduced resting cells did not express c-myc. The c-myc protein was observed in the highest amount at the proliferative B-lymphoblast stage of maturation and was reduced in plasmablasts and undetectable in plasma cells. The results suggest that maturation of B cells into nonproliferative, terminally differentiated plasma cells is associated with a downregulated c-myc expression and thus support the view that the deregulated c-myc gene in BL and MPC is expressed at an inappropriate stage of maturation and thereby inhibits terminal differentiation. PMID- 1899808 TI - Inhibition of mutagenicity in Salmonella typhimurium and skin tumor initiating and tumor promoting activities in SENCAR mice by glycyrrhetinic acid: comparison of 18 alpha- and 18 beta-stereoisomers. AB - Licorice has been used as medicine and as sweetening agent in food products. The major water-soluble constituent of licorice is glycyrrhizin (GL), an oleanane triterpenoide, which is known to be partly hydrolyzed by glucuronidase to its aglycone glycyrrhetinic acid (GA) which exists in 18 alpha (alpha-GA) and 18 beta (beta-GA) stereoisomeric forms. In this study alpha-GA and beta-GA were found to inhibit the mutagenicity of benzo[a]pyrene (B[a]P), 2-aminofluorene and aflatoxin B1 in Salmonella typhimurium TA98 and TA100. beta-GA was more effective than alpha-GA as an antimutagen. In the two-stage skin tumorigenesis protocol using 7,12-dimethylbenz[a]anthracene (DMBA) as the tumor initiating agent followed by twice weekly applications of 12-O-tetradecanoylphorbol-13-acetate as tumor promoter, pretreatment of SENCAR mice with alpha-GA or beta-GA resulted in significant protection against tumor initiation as well as tumor promotion. As an anti-tumor initiating agent, beta-GA was found to be more effective than alpha GA. Similarly, topical application of beta-GA was found to be more effective than alpha-GA in inhibiting the binding of both [3H]B[a]P and [3H]DMBA to epidermal DNA. However, as an anti-tumor promoter, alpha-GA and beta-GA showed comparable effects. Our results suggest that both alpha-GA and beta-GA possess substantial anti-skin tumor initiating and anti-skin tumor promoting activities. PMID- 1899809 TI - Comparative biotransformation of aflatoxin B1 in mammalian airway epithelium. AB - Aflatoxin B1 (AFB1) appears to be a risk factor for upper respiratory tumors in individuals occupationally exposed to AFB1-contaminated grain dusts. To study the potential effects of this mycotoxin in the upper airways, the metabolism of AFB1 was investigated in tracheal cultures and purified tracheal microsomes from rabbit, hamster and rat. These species differ in the proportion of P450 containing non-ciliated epithelial (NC) cells in the upper airway (17, 41, 0% respectively). Cultures from the rabbit produced the highest level of the AFB1 metabolites AFB1-dihydrodiol (AFB1-diol), GSH-AFB1, AFM1, AFB2a and the highest tracheal microsomal pentoxyresorufin-O-dealkylase (PROD) activity (an indicator of that P450 activity which activates AFB1) and greater cytosolic GSH-transferase activity compared to hamster and rat. Tracheal microsomal epoxide hydrolase activity, AFB1-diol production, cytochrome P450 content, P450 reductase and ethoxyresorufin-O-dealkylase (EROD) activity (an indicator of AFB1 detoxification) were highest in the hamster. Although the overall metabolic activity in rat tracheal epithelium was low, PROD-related activity appeared to predominate. Conjugation with GSH was the major detoxification pathway in rabbit and rat upper airways, although levels of AFB1-GSH and activities of glutathione transferase were significantly lower in the rat than in the rabbit and hamster. Hydrolysis of the putative AFB1-2,3-epoxide via epoxide hydrolase appeared to be the major AFB1 detoxification pathway in hamster tracheal epithelium as indicted by corresponding high tracheal microsomal AFB1-diol production and EH activity compared to rabbit and rat. Glucuronide and sulfate conjugates of AFB1 and its metabolites were formed in tracheal explant cultures from these three species, although amounts formed were minor. These results indicate that rabbit upper airway epithelium contains metabolic activity primarily involved in AFB1 activation, whereas AFB1 detoxification pathways predominante in hamster. Furthermore, the characteristics of carcinogen metabolism are not predictable based solely on airway morphology. PMID- 1899810 TI - The potent anti-tumor-promoting agent isoliquiritigenin. AB - A topical application of a chalcone derivative, 4,2',4'-trihydroxychalcone (isoliquiritigenin) inhibited epidermal ornithine decarboxylase (ODC) induction and ear edema formation, i.e. inflammation, caused by a topical application of 12 O-tetradecanoylphorbol-13-acetate (TPA) in CD-1 mice. In addition, isoliquiritigenin potently inhibited 7,12-dimethylbenz[alpha]anthracene (DMBA) initiated and TPA-promoted skin papilloma formation. This inhibitory effect of isoliquiritigenin was not due to any damage inflicted on the initiated cells but due to its anti-tumor-promoting action. Isoliquiritigenin also inhibited epidermal ODC induction and skin tumor promotion caused by 7 bromomethylbenz[alpha]anthracene (BrMBA), a non-TPA type of tumor-promoting agent, in DMBA-initiated mice. Isoliquiritigenin inhibits neither 12-lipoxygenase nor cyclooxygenase in epidermal subcellular fractions. This compound, however, inhibited TPA-stimulated prostaglandin E2 (PGE2) production in intact epidermal cells. ODC induction caused by TPA was inhibited by a topical application of cyclooxygenase inhibitor, indomethacin. Inhibition of ODC induction by indomethacin was counteracted by a topical application of PGE2, while inhibition caused by isoliquiritigenin was not overcome by PGE2. The results suggest that a mechanism other than the inhibition of PGE2 production is involved in the anti tumor-promoting action of isoliquiritigenin. Isoliquiritigenin failed to inhibit phospholipase A2 activity of platelet sonicates, but inhibited platelet 12 lipoxygenase and 5-lipoxygenase in polymorphonuclear leukocytes. Therefore, it might be possible that isoliquiritigenin exerts its anti-tumor-promoting action through the lipoxygenase inhibition by acting on cells other than the target epidermal cells. Our present results, in combination with our previous data, demonstrate that some chalcone derivatives and flavonoids which show a potent lipoxygenase inhibitory action act on a common step in the skin tumor promotion caused by two different types of tumor-promoting agents, i.e. TPA and BrMBA, and suggest that these compounds show promise as drugs to prevent tumor promotion. PMID- 1899812 TI - The development of a human cell line stably expressing human CYP3A4: role in the metabolic activation of aflatoxin B1 and comparison to CYP1A2 and CYP2A3. AB - We have developed a human lymphoblastoid cell line, designated 3A4/Hol, which stably expresses human CYP3A4 cDNA. This cell line exhibited testosterone 6 beta hydroxylase activity, produced immunologically detectable CYP3A4 protein and was more sensitive to the cytotoxicity and mutagenicity of the carcinogenic mycotoxin aflatoxin B1 (AFB1) than was the parent cell line. The concentration-response for AFB1 cytotoxicity and mutagenicity in 3A4/Hol cells was compared to the responses of isogenic cell lines expressing comparable levels of human CYP1A2 (1A2/Hyg cells) and human CYP2A3 (2A3/Hyg cells). 1A2/Hyg cells were 3- to 6-fold more sensitive than 3A4/Hol cells to AFB1-induced mutation. 3A4/Hol cells were 10- to 15-fold more sensitive to AFB1-induced mutation than 2A3/Hyg cells. The differences in mutagenicity were supported by the relative binding of [3H]AFB1 to cellular DNA. PMID- 1899811 TI - 7-Sulfooxymethyl-12-methylbenz[a]anthracene is an electrophilic mutagen, but does not appear to play a role in carcinogenesis by 7,12-dimethylbenz[a]anthracene or 7-hydroxymethyl-12-methylbenz[a]anthracene. AB - Although a bay-region dihydrodiolepoxide metabolite has been considered as a principal ultimate electrophilic and carcinogenic form of 7,12 dimethylbenz[a]anthracene (DMBA), other reactive metabolites might also play a role in the activation of this hydrocarbon in vivo. Earlier studies suggested the hydroxylation of a meso-anthracenic methyl group with subsequent formation of a benzylic ester bearing a good leaving group (e.g. sulfate) as a metabolic activation pathway for DMBA. In support of this hypothesis, the formation of an electrophilic and mutagenic sulfuric acid ester of 7-hydroxymethyl-12 methylbenz[a]anthracene (HMBA) by rat liver cytosolic sulfotransferase activity has previously been demonstrated, but no data have been reported on the carcinogenicity of this reactive ester. In the present study, we compared the carcinogenicity of chemically synthesized sodium 7-sulfooxymethyl-12 methylbenz[a]anthracene (SMBA) with that of the parent methyl and hydroxymethyl hydrocarbons. For this purpose, tests were made in several animal tumor models: induction of hepatomas in male B6C3F1 mice, lung adenoma induction in A/J mice, initiation of mouse skin tumors, development of sarcomas in rats at the injection sites, and initiation of preneoplastic enzyme-altered foci in rat liver. Data from all of these studies indicate that SMBA is not more carcinogenic than DMBA or HMBA. In addition, the carcinogenic activity of HMBA was not altered by dehydroepiandrosterone, a strong inhibitor of sulfotransferase activity for HMBA. DMBA produced only a low level of hepatic benzylic DNA adducts in rats when a relatively high dose was administered. These adducts constitute less than 5% of total DMBA residues bound to hepatic DNA. The rest of the adducts appear to be associated with other electrophilic intermediates including the dihydrodiol epoxide metabolites. Based on the results of our present study, it is unlikely that DMBA exerts its carcinogenic activity via metabolic activation to SMBA. PMID- 1899813 TI - Combination of blocking agents and suppressing agents in cancer prevention. AB - The design of the present study was based on the premise that if blocking agents and suppressing agents are targeted at different phases of chemical carcinogenesis, a greater chemopreventive effect would be achieved by using the combination treatment compared to the single-agent treatment. The dimethylbenz[a]anthracene (DMBA)-induced mammary tumor model in rats was used to test this hypothesis, with the blocking agent given before DMBA only and the blocking agent given after DMBA until the end of the experiment. A total of three sets of combination treatment were carried out; diallyl sulfide/Se methylselenocysteine, ellagic acid/selenomethionine, and diallyl sulfide/quercetin. In all three cases, the combination regimen was much more effective than the single-agent treatment in tumor suppression. It should be noted that only naturally occurring inhibitors were selected for these experiments. The impact of minor dietary anutrients in cancer chemoprevention is also discussed. PMID- 1899814 TI - Mycoplasma pneumoniae infections and Stevens-Johnson syndrome. Report of eight cases and review of the literature. AB - On the basis of a literature review and eight cases of our own, we analyzed 37 cases of Mycoplasma pneumoniae (MP) infection and Stevens-Johnson syndrome (SJS). Our clinical and laboratory findings do not differ from those reported in the literature for MP infection with no exanthem or for SJS of various etiologies. Eighty percent of the children presented with symptoms of upper respiratory tract infection (URTI) (cough, fever, sore throat, malaise, headache), with a mean of 10 days (range 1 to 30) before skin rash broke out. Skin manifestations occurred in 94.2% of the patients after 3 to 21 days (mean 10.3 days) of fever. The exanthem, composed predominantly of maculopapular and vesicular, was distributed chiefly on the trunk and extremities and lasted less than 14 days in 87.8% of the patients. Stomatitis was observed in 91.6% of the patients and conjunctivitis in 50%. No consistent pattern seems to emerge by which one could predict the existence of MP infection causing SJS. The complications of SJS associated with MP seem less frequent (2.7%) and much less severe than in cases where SJS arises from other reported causes. Because coincidence cannot be excluded from the assessments of the degree and rate of improvement for the few patients treated with corticosteroid, from the low frequency of complications, and from the mortality rate of zero in this series of patients, the use of corticosteroids for SJS associated with MP infection is questionable. PMID- 1899815 TI - Gonococcal salpingitis in a premenarchal female following sexual assault. PMID- 1899816 TI - Identifying patients with high risk of high cost. PMID- 1899817 TI - Hypoxic pulmonary vasoconstriction in systemic sclerosis and primary pulmonary hypertension. AB - Reduction of pulmonary vascular resistance by a high inspired oxygen concentration is a common, but not universal phenomenon in patients with pulmonary vascular disease of varying etiology that may determine their response to long-term domiciliary oxygen therapy. We therefore determined changes in PVR during oxygen therapy in two patient populations not previously studied: systemic sclerosis (n = 8, mean age +/- SEM, 44.5 +/- 5.4 years) and primary pulmonary hypertension (n = 7, mean age +/- SEM 38 +/- 7.8 years). All patients were hypoxemic (arterial oxygen tension, on air 9.5 +/- 1.2 kPa for SSc and 8.3 +/- 0.6 kPa for PPH, p greater than 0.05). Right atrial pressure, pulmonary artery pressure, pulmonary artery occlusion pressure, systemic arterial pressure, PaO2 and cardiac output by thermodilution were measured at three, 20-min intervals while inspiring air and again after inspiring 60 percent oxygen for 30 min. The PVR fell significantly with oxygen in patients with SSc from 797.6 +/- 179.2 to 610 +/- 151.6 dynes/s/cm-5 (p less than 0.01), and this fall correlated with baseline PAP and PaO2 prior to oxygen therapy (r = 0.86, p less than 0.025; r = 0.77, p less than 0.05, respectively). In patients with PPH, there was no significant fall in PVR with oxygen (from 969 +/- 80.2 to 851.9 +/- 91.2 dynes/s/cm-5, p greater than 0.05) and no predictor of a vasodilator response in individual patients. In SSc, hypoxic pulmonary vasoconstriction contributes more consistently to elevated PVR than in patients with PPH. PMID- 1899818 TI - Variability of breathlessness measurement in patients with chronic obstructive pulmonary disease. AB - The purpose of our study was to evaluate the reproducibility of a Borg rating of dyspnea in patients with COPD. We examined nine patients with COPD who performed a SST on four separate days within a ten-day period. The patients walked on a treadmill for 6 min. At the end of each minute, patients matched a Borg rating to the intensity of their breathlessness. We measured the HR, VE, VO2, VT and f at the end of each minute. While the mean VO2, VE, HR, VT and f stabilized after one or two attempts, the Borg ratings decreased with successive tests. We conclude that the Borg scale for measuring breathlessness shows progressive decreases with repetition whereas VO2, VE, HR, VT and f stabilize after one or two practice attempts. This suggests that desensitization to dyspnea may play a role in the improvement of patients after exercise. PMID- 1899819 TI - Serum adenosine deaminase in viral and bacterial pneumonia. AB - We measured the activity of serum adenosine deaminase (ADA) in paired sera from 171 military conscripts with radiographically verified pneumonia. Patient serum samples were selected on the basis of serologic analyses identifying as single etiologic agents Streptococcus pneumoniae in 29 patients, Haemophilus influenzae in 7, Mycoplasma pneumoniae in 43, adenovirus in 24, influenza A or B in 12, and parainfluenza in 5 patients. In 14 patients Neisseria meningitidis and in 31 Chlamydia spp were considered the main etiologic agent. Compared with a control group of 45 healthy men, the ADA activity in patients with pneumonia was significantly higher (p less than 0.001) in all patient groups except those with meningococcal pneumonia. The highest ADA levels were seen in patients with pneumonia caused by M pneumoniae (27.4 +/- 9.7 U/L), Chlamydia spp (26.3 +/- 9.1 U/L), and adenovirus (28.5 +/- 10.9 U/L) compared with the controls (11.1 +/- 3.0 U/L). In patients with meningococcal pneumonia, the ADA activity was significantly decreased (p less than 0.001). Serum ADA activity probably reflects differences in cellular immune response to different infectious agents. The ADA determinations may give corroborative information on the etiologic agent of pneumonia. PMID- 1899820 TI - Combined nasal intermittent positive-pressure ventilation and rocking bed in chronic respiratory insufficiency. Nocturnal ventilatory support of a disabled person at home. AB - The use of intermittent positive-pressure ventilation via nasal mask with a rocking bed provided the necessary ventilatory support for a person with quadriplegia living at home. This option was required to maintain an independent life-style of choice. The combination of techniques and the linkage of devices demonstrated an effective use of simple available technology for respiratory care at home and the adaptation of the respiratory prescription to the total needs of each person: medical, social, and financial. The further use of nasal mask ventilation in selected cases is encouraged by clinical research protocol. PMID- 1899821 TI - Intermittent abdominal pressure ventilator in a regimen of noninvasive ventilatory support. AB - The purpose of this work is to present 640 patient-years of experience using the intermittent abdominal pressure ventilator (IAPV) in a regimen of noninvasive ventilatory support for patients with paralytic/restrictive respiratory insufficiency. Fifty-two of the 54 patients who used the IAPV used 24-hour noninvasive ventilatory support. Thirty-eight of the 52 patients could tolerate less than 15 minutes of free time off their ventilators except by the successful use of glossopharyngeal breathing (GPB). No patient, however, retained an indwelling tracheostomy and none required or used supplemental oxygen therapy. Forty-eight of the 54 patients used the IAPV for daytime support for a mean of 12.9 +/- 11.5 years (3 months to 39 years) while using other forms of noninvasive support overnight. All 48 patients maintained normal minute ventilation and end tidal PCO2 on the IAPV. One patient used the IAPV only for nocturnal ventilatory support for six months. Five patients relied on the IAPV as their sole method of ventilatory support 24 hours a day for a mean of 13.4 +/- 11.2 years (range, 2 to 31 years). Three of these five patients had no free time and were studied by nocturnal SaO2 monitoring that demonstrated a mean SaO2 of 95 percent or greater and a minimum SaO2 of 86 percent. The maximum end-tidal PCO2 was 49 mm Hg during sleep on the IAPV. The 48 patients receiving daytime IAPV support reported few difficulties. However, two of the five patients using the IAPV 24 hours a day had development of sacral decubiti. The IAPV became ineffective for 12 patients after 12.3 +/- 9.5 years of use. These patients then switched to daytime mouth IPPV. We conclude that the IAPV is a safe and effective method of long-term daytime ventilatory support for patients with paralytic/restrictive respiratory insufficiency. Its use is optimized when employed in combination with other noninvasive methods of ventilatory support, thus eliminating the need for tracheostomy, and optimizing the use of GPB. Regular follow-up is important because the IAPV can become less effective with time. PMID- 1899822 TI - Intermittent volume cycled mechanical ventilation via nasal mask in patients with respiratory failure due to COPD. AB - Intermittent mechanical ventilation via nasal CPAP mask was provided to 13 patients admitted to this institution for exacerbation of chronic respiratory failure. Ten suffered from COPD, two suffered from obesity hypoventilation syndrome (OHS), and one from severe hypothyroidism. All except one presented with dyspnea and hypercapnia due solely to progression of their underlying disease processes. Six of the patients with COPD and the patient with hypothyroidism responded to positive pressure ventilation by mask with improvements in blood gas values and clinical status. The remaining two patients with COPD and the two patients with OHS were unable to use the system. Four of the patients with COPD and chronic respiratory failure have been subsequently maintained on daily volume ventilation via nasal mask for about 20 months with persistent clinical and physiologic improvements. Application of volume ventilation through the nasal CPAP mask is a feasible strategy for providing long-term mechanical ventilation to selected patients with COPD and respiratory failure. PMID- 1899823 TI - The effect of duodenojejunal alimentation on gastric pH and hormones in intensive care unit patients. AB - We evaluated effects of duodenojejunal (DJ) feeding on gastric pH and selected gastrointestinal hormones in 13 randomly selected patients in an intensive care unit (ICU). To obtain baseline values for gastric pH, a nasogastric (NG) tube was placed in each patient and gastric pH was measured every 30 minutes for 2 hours. To obtain control values, a Dobbhoff tube was placed fluoroscopically and 0.45 percent saline solution (NaCl), 75 ml, was infused for 1 hour and gastric pH was measured again; the previously placed NG tube was left in position. Then, by randomization, either 0.45 percent NaCl (pH = 5) was continued (n = 6) or a high nitrogen, isotonic, enteral feeding solution (Osmolite HN, pH = 6.4) (n = 7) was infused, both at 75 ml/h. Gastric pH was noted hourly for 96 hours; antacid (Maalox TC, 15-ml aliquots) was given by NG tube when the pH was 4 or less. After 96 hours, the infusion was stopped and gastric pH was noted for 4 additional hours. Before and during initial saline solution infusion; after 24, 48, 72, and 96 hours of continuous infusion; and 4 hours after stopping the infusion, peripheral venous blood was obtained for measurement of plasma gastric inhibitory polypeptide (GIP) and serum gastrin. Data were analyzed by ANOVA (RMD), Fishers' exact test, and the unpaired t-test. Groups did not differ demographically. Throughout the infusion, gastric pH tended to be higher with the enteral feeding solution than with saline solution, but this was significant only at 24 hours. Less antacid was required with the enteral feeding solution at 24 and 48 hours than with saline solution. Plasma GIP levels were significantly higher with the enteral feeding solution than with saline solution during most of the infusion. Serum gastrin levels did not differ between the groups. In this cohort, infusion of the enteral feeding solution tended to maintain a gastric pH of more than 4 and was associated with increased plasma GIP levels, which may inhibit gastric acid secretion. Early enteral feeding may benefit certain ICU patients. PMID- 1899824 TI - Continual trending of Fick variables in the critically ill patient. AB - We continually monitored components of the Fick equation (oxygen consumption, arterial and mixed venous oxygen saturation) simultaneously in ten hemodynamically stable, mechanically ventilated postoperative patients in order to evaluate our ability to continually calculate cardiac output (Qc) from its Fick determinants. Qc underestimated (p less than 0.001) cardiac output calculated from intermittent CO-oximeter measurements (6.2 vs 6.4 L/min) with good correlation (r = .96), while it consistently overestimated (p less than 0.05) thermodilution cardiac output (Qtd) (6.2 vs 5.9 L/min, r = .84). Measured oxygen consumption correlated with Qtd (r = .78) nearly as well as did Qc, while mixed venous oxygen saturation correlated poorly with Qtd (r = -.10). Trends of multiple Fick variables were helpful in interpreting changes in a single parameter. We conclude that continual trending of Fick variables in critically ill patients is both feasible and useful and that Qc agrees well with both traditional Fick cardiac output computed from CO-oximetry data and thermodilution measurements. Finally, measured oxygen consumption, available continuously, correlates well with changes in cardiac output in this subset of critically-ill patients. PMID- 1899825 TI - Effects of hydralazine and increased cardiac output on recombinant tissue plasminogen activator-induced thrombolysis in canine pulmonary embolism. AB - We employed a canine model of pulmonary embolism, induced by injection of autologous radiolabelled blood clots, to investigate effects of hydralazine and an increase in cardiac output per se on recombinant tissue plasminogen activator induced thrombolysis. Emboli increased pulmonary artery pressure (PAP) and decreased CO from 2.7 to 1.8 L/min-1. Following embolization, dogs were randomly divided into three groups. Group 1 received .5 mg/kg of rtPA over 30 minutes. Group 2 received the same dose of rtPA and were pretreated with hydralazine to increase CO approximately 50 percent. In the group 3 dogs, CO was increased by opening a systemic A-V fistula. Following embolization, CO remained low in group 1, the mean 2 h time-averaged CO was 1.9 L/min-1. The CO was 2.9 and 3.1 L/min-1 in groups 2 and 3, respectively. Corresponding to the increased flow in groups 2 and 3, rate and extent of pulmonary thrombolysis significantly increased. These results indicate that an increase in CO augments rtPA-induced pulmonary thrombolysis. PMID- 1899826 TI - Response of diffusion capacity in the treatment of tropical eosinophilia. PMID- 1899827 TI - The psychosocial treatment of recurrent diabetic ketoacidosis: an interdisciplinary team approach. AB - The professional expertise of the diabetes mental health professional is integral to the interdisciplinary team approach to recurrent diabetic ketoacidosis (DKA). A case report provides the context to illustrate the interconnection of concurrent strategies of diabetes management, teaching, and counseling. Specific methods include a practical approach to manipulative behavior in blood glucose monitoring, supervision of insulin administration, education, and intensive psychotherapy. In this case study, the adolescent's removal from her home environment, along with medical supervision and extensive psychosocial support, was instrumental in reversing the pattern of self-destructiveness. Recurrent DKA is a very specific problem for which the mental health professional can play an effective treatment role. PMID- 1899828 TI - Suppression of dexamethasone-stimulated DNA synthesis in an oncogene construct containing rat cell line by a DNA site-oriented ligand of poly-ADP-ribose polymerase: 6-amino-1,2-benzopyrone. AB - The cellular inhibitory effects of 6-amino-1,2-benzopyrone (6-ABP), a DNA site specific ligand of adenosine diphosphoribosyl transferase (ADPRT), were determined in a dexamethasone-sensitive EJ-ras gene construct containing cell line (14C cells). Dexamethasone in vitro transforms these cells to a tumorigenic phenotype and also stimulates cell replication. At a non-toxic concentrations (0.2 mM) 6-ABP treatment of intact cells for 4 days inhibits the dexamethasone stimulated increment of cellular DNA content, depresses replicative DNA synthesis as assayed by thymidine incorporation to the level of cells that were not exposed to dexamethasone, and in permeabilized cells reduces the dexamethasone-stimulated increase of deoxyribonucleotide incorporation into DNA to the level of untreated cells. In situ pulse labeling of cells pretreated with 6-ABP indicated an inhibition of DNA synthesis at a stage prior to the formation of the 10-kb intermediate species. The drug had no direct effect on cellular DNA polymerases as tested in vitro, and the inhibition of DNA synthesis in permeabilized cells following drug treatment for 4 days was abolished by externally added DNA templates. Neither dexamethasone nor the drug influenced the cellular quantity of ADPRT molecules, tested immunochemically. PMID- 1899829 TI - Induction of reinitiation of meiosis in amphibian Bufo and Xenopus oocytes by injection of M-phase extracts of ciliate Tetrahymena needs the recipient protein synthesis. AB - We show here that germinal vesicle breakdown of amphibian Bufo and Xenopus oocytes can be induced if ciliate Tetrahymena extracts are injected into them. The activity of meiosis-reinitiation-inducing factor (MRIF) appeared only a M phase of a synchronously dividing culture, indicating that this MRIF has an important function for induction of M-phase in the mitotic cell cycle. MRIF of Tetrahymena differed from MPF (M-phase-promoting factor), because its action on the induction of GVBD was inhibited by cycloheximide and it could not induce GVBD in starfish oocytes by microinjection. MPF activity was not detected in extracts of vegetatively growing Tetrahymena. Preliminary experiments showed that MRIF was a heat-labile, Ca2(+)-sensitive, and trypsin-sensitive soluble protein. PMID- 1899830 TI - Antibodies against Tetrahymena 14-nm filament-forming protein recognize the replication band in Euplotes. AB - Tetrahymena 14-nm filament-forming protein (49K protein) is a structural protein which is involved in activity of the pronuclei during conjugation (O. Numata, T. Sugai, and Y. Watanabe (1985) Nature (London) 314, 192-194). Using monoclonal and polyclonal antibodies, we here demonstrate the presence of a cross-reactive protein (CRP-49) within the macronuclear replication bands of Euplotes harpa and E. eurystomus which is recognized by anti-49K protein antibodies. Immunoblotting reveals that both monoclonal and polyclonal antibodies cross-react to a protein with an apparent molecular mass of 50 kDa in an E. harpa cell extract and to a protein of 49 kDa in a macronuclear extract of E. eurystomus. The antibodies used in this study have no effect upon in vitro DNA synthesis in the replication band of E. eurystomus. PMID- 1899831 TI - Ciprofloxacin inhibits human hematopoietic cell growth: synergism with tumor necrosis factor and interferon. AB - The cytokines tumor necrosis factor (TNF) and interferon (IFN) induce antiproliferative and cytotoxic activity in a variety of cell types. Ciprofloxacin (CFN)--a new fluoroquinolone antibiotic--has also been described, at high concentrations, to suppress hematopoietic cell growth and to affect cytokine production. This study examines the possible relationship between TNF alpha and IFN gamma, as components of host defense mechanisms, and CFN. To investigate the effect of CFN, either alone or combined with TNF or IFN, on normal human hematopoiesis, we examined in vitro changes in hematopoietic progenitor cell growth. We also studied the effect of CFN on human cytokine production by determining TNF, IFN, and colony-stimulating factor (CSF) production by human mononuclear leukocytes (MNC). Granulocyte and monocyte colony formation (granulocyte-macrophage colony-forming cells, GM-CFC) as well as erythroid burst formation (erythroid burst-forming units, BFU-E) were inhibited only by high nontherapeutic levels of CFN. Lower CFN concentrations, however, were inhibitory in the presence of low, noninhibitory concentrations of human recombinant (r)IFN gamma or rTNF alpha. CFN induced a striking dose-dependent increase in IFN gamma production and a decrease in CSF production by mitogen stimulated MNC. No effect was observed, however, on TNF production by stimulated MNC. The synergistic inhibition of hematopoietic progenitor cell proliferation, achieved by combining low doses of CFN and of antiproliferative cytokines, may explain the occasional case of leukopenia or anemia observed in infected patients receiving CFN. This effect may also indicate the applicability of such a combination against malignant cell growth. PMID- 1899832 TI - Myocardial disease and catecholamine metabolism in JCR:LA-corpulent rat. AB - The JCR:LA-cp rat is a strain carrying the mutant cp (corpulent) gene. Animals that are homozygous cp are hyperphagous, hyperinsulinemic, hyperlipidemic, and obese. Corpulent male rats, but not females or lean rats, develop atherosclerotic lesions and myocardial lesions. Since the myocardial lesions are apparently of ischemic origin, the noradrenergic system and vascular hyperactivity and vasospasm may play a role in the pathogenesis. To test this we have studied the brain contents of the amines norepinephrine, dopamine, and 5-hydroxtryptamine and their breakdown products and depleted the peripheral sympathetic terminals with 6 hydroxydopamine. Only 5-hydroxytryptamine and 5 hydroxyindole-3-acetic acid were present at higher concentrations in the corpulent rats with depressed levels of dopamine in very young or old lean rats. The activity of monoamine oxidase may provide an indication of nonadrenergic activity in tissue. The activity in the heart increased with age and was higher in the corpulent rats than in the lean at all ages. Activity in aorta was independent of age or genotype. Long term treatment with 6-hydroxydopamine caused marked depletion of norepinephrine in the heart with only a slight decrease in brain concentration. There were no effects on the hyperlipidemia or hyperinsulinemia that are strongly associated with vascular and myocardial disease. The myocardial lesion frequency in corpulent rats was not altered by the chemical sympathectomy. The results suggest that norepinephrine and the sympathetic nervous system are probably not involved in the generation of the myocardial lesions or metabolic abnormalities in this strain of rat. PMID- 1899833 TI - Immune activation and the anaemia associated with chronic inflammatory disorders. AB - Chronic inflammatory disorders are associated with an increased risk of patients developing anaemia. There is some evidence that cytokines released during cell mediated immune responses are capable of inhibiting bone marrow haematopoiesis. In vitro, interferon gamma and tumour-necrosis factor alpha inhibit growth of erythroid precursor cells. The mode of action of these cytokines is probably associated with their antiproliferative capacity. Decrease of serum iron and increase of storage iron in patients appears to be a consequence of the defense strategy of macrophages during long-lasting inflammatory disorders. Decreased serum iron correlates to decreased haemoglobin concentrations. In view of this, the development of anaemia seems likely to result from the altered iron metabolism induced by stimulated macrophages. Low haemoglobin levels and associated hypoxia up-regulate the release of erythropoietin, which can explain why increased circulating erythropoietin is usually found in patients with anaemia. PMID- 1899834 TI - The oxygenation of cholesterol esters by the reticulocyte lipoxygenase. AB - The arachidonate 15-lipoxygenase from rabbit reticulocytes oxygenates cholesterol esters containing polyenoic fatty acids. Cholesterol esterified with saturated fatty acids is not oxygenated. The structures of the oxygenation products formed from various cholesterol esters have been identified by high pressure liquid chromatography, UV-spectroscopy and gas chromatography/mass spectroscopy. Oxygenated cholesterol esters have been detected in atherosclerotic plaques of human aortas. PMID- 1899835 TI - Modulation of protease specificity by a change in the enzyme microenvironment. Selectivity modification on a model substrate, purified soluble proteins and gluten. AB - Subtilisin BPN' activity on a synthetic substrate is found to decrease with the concentration of soluble additives such as sugars and polyols, the catalytic efficiency of the enzyme being related to the water activity in the reaction medium. Limited hydrolysis of B chain of insulin is followed and the cleavage priority determined. When carried out in glycerol-containing medium, both enzyme catalytic behaviour and specificity are perturbed; a different cleavage order and a selectivity restriction are observed. The experiments were generalised to purified proteins and to an insoluble protein complex. The hydrolysis kinetics of purified gliadins by pepsin and of gluten by a Bacillus neutral protease are modulated in presence of water activity depressors. Glycerol is able to increase both pepsin efficiency and gluten protein solubility. The hydrolysis order is affected by water-structuring molecules in the enzyme microenvironment and new peptides appear whatever the size and initial solubility of the substrate. PMID- 1899836 TI - Characterization of a novel zinc binding site of protein kinase C inhibitor-1. AB - The zinc-binding properties of an endogenous protein inhibitor of protein kinase C was studied. Equilibrium gel penetration revealed that 1 mol of this protein binds 0.97 mol of zinc with a dissociation constant of 4.3 microM. The site of zinc-binding, MVVNEGSDGGQSVYHVHLHVLGGR, was identified by a multi-step process consisting of tryptic digestion, fragment isolation, transfer to nitrocellulose, and hybridization with 65ZnCl2. Binding of 65ZnCl2 to selected synthetic fragments further localized the site of interaction to the sequence QSVYHVHLHVL. This region contains 3 closely positioned histidine residues and represents a novel zinc-binding site. PMID- 1899837 TI - ATP-dependent leukotriene export from mastocytoma cells. AB - The biosynthesis of leukotrienes (LT) C4 and B4 is followed by an export of these mediators into the extracellular space. This transport was characterized using plasma membrane vesicles prepared from mastocytoma cells and identified as an ATP dependent primary active process. The apparent Km-values were 110 nM for LTC4 and 48 microM for ATP. The transport rate was highest for LTC4, whereas LTD4, LTE4, and N-acetyl-LTE4 were transported with relative rates of 31, 12 and 8%, respectively, at a concentration of 10 nM. LTB4 transport was also dependent on ATP. LTC4 transport was inhibited by LTD4 receptor antagonists (IC50 = 1.0 microM for MK-571 and 1.3 microM for LY245769) and by the inhibitor of leukotriene biosynthesis MK-886 (IC50 = 1.8 microM). The ATP-dependent export carrier for leukotrienes in leukotriene-synthesizing cells represents a novel member of the family of ATP-dependent exit pumps. PMID- 1899838 TI - GO associates with another 40 kDa brain protein. AB - Guanine nucleotide binding proteins (G proteins) mediate a variety of cellular responses to external stimuli. Pure G protein, receptor, and effector are sufficient to reconstitute hormonal activation of an effector in phospholipid vesicles, but other components may be important for specificity or localization in vivo. If another protein associates with GO, the molecular weight of GO solubilized from membranes would be larger than the molecular weight of GO after purification. We find that GO solubilized from bovine brain membranes by Triton X 100 behaves as a single population of molecules on sucrose density gradients and gel filtration columns. Its molecular mass is about 40 kDa larger than pure GO. Association of GO with the other protein is fragile as the proteins dissociate on further purification. There was no difference in ADP-ribosylation or tryptic cleavage of GO in larger and smaller form. These studies provide a basis for future experiments to stabilize the interaction and identify the protein. PMID- 1899839 TI - Hormonal control of gene expression: interactions between two trans-acting regulators in Drosophila. AB - The steroid hormone 20-hydroxyecdysone (20HE) and the Broad-Complex locus (BRC) are involved in regulating developmental changes in gene expression around the time of metamorphosis in Drosophila. We have investigated the regulatory interactions between 20HE, BRC, and a set of genes expressed in the fat body of third-instar Drosophila larvae. RNA levels for two hormone-inducible genes, Larval Serum Protein-2 and P1, accumulate to normal levels in BRC-mutant larvae. In contrast, RNA levels for the P6 gene were affected by mutations at BRC. On the basis of the results of experiments in which hormone concentrations were varied in BRC-mutant or wild-type larvae, we conclude that 20HE can both increase and decrease P6 RNA levels in the absence of BRC product(s). BRC appears to be a trans-acting modulator of the response of P6 to the hormone. We propose that BRC attenuates the repressive effect of the hormone, expanding the range of hormone concentrations that induce the gene, thus allowing P6 RNA to reach high levels during the third larval instar. The results are discussed in relation to other genes that are regulated by the same two trans-acting factors. A model is presented that refines the model of Ashburner et al. (1974, Cold Spring Harbor Symp. Quant. Biol. 38: 655-662) for the hormonal regulation of gene activity. PMID- 1899840 TI - A unique zinc finger protein is associated preferentially with active ecdysone responsive loci in Drosophila. AB - Using an immunochemical approach, we have identified a unique antigen, PEP (protein on ecdysone puffs), which is associated in third-instar larvae with the active ecdysone-regulated loci on polytene chromosomes; PEP is not associated with most intermolt puffs and is found on some, but not all, heat shock-induced puffs. The distribution pattern changes with changing puffing patterns in the developmental program. We have screened an expression library and recovered a cDNA clone encoding PEP. PEP possesses multiple potential nucleic acid- and protein- binding regions: a glycine- and asparagine-rich amino terminus, four zinc finger motifs, two very acidic segments, two short basic stretches, and an alanine- and proline-rich carboxyl terminus. The Pep gene maps by in situ hybridization to the cytological locus 74F, adjacent to the early ecdysone responsive region; however, the gene is not regulated by ecdysone at the level of transcription. The pattern of Pep expression through development suggests that maternal Pep gene transcripts are supplied to the embryo, and that the abundance of Pep gene transcripts decreases to a lower, fairly constant level thereafter. This unusual protein may play a role in the process of gene activation, or possibly in RNA processing, for a defined set of developmentally regulated loci. PMID- 1899841 TI - Analysis of arginine-rich peptides from the HIV Tat protein reveals unusual features of RNA-protein recognition. AB - Arginine-rich sequences are found in many RNA-binding proteins and have been proposed to mediate specific RNA recognition. Fragments of the HIV-1 Tat protein that contain the arginine-rich region of Tat bind specifically to a 3-nucleotide bulge in TAR RNA. To determine the amino acid requirements for specific RNA recognition, we synthesized a series of mutant Tat peptides spanning this domain (YGRKKRRQRRRP) and measured their affinity and specificity for TAR RNA. Several corresponding mutations were introduced into the full-length Tat protein, and trans-activation activity was measured. Systematic substitution of arginine residues with alanines or lysines suggested that overall charge density is important but did not point to any specific residues as being essential for binding. A glutamine-to-alanine substitution had no effect on binding. Remarkably, peptides with scrambled or reversed sequences showed the same affinity and specificity for TAR RNA as the wild-type peptide. Trans-activation activity of the mutant Tat proteins correlated with RNA binding. Arginine-rich peptides from SIV Tat and from HIV-1 Rev, which can functionally substitute for the basic region of HIV-1 Tat, also bound specifically to TAR. Circular dichroism spectra suggest that the arginine-rich region of Tat is unstructured in the absence of RNA, becomes partially or fully structured upon binding, and induces a conformational change in the RNA. These results suggest that arginine-rich RNA binding domains have considerable sequence flexibility, reminiscent of acidic domains found in transcriptional activators, and that RNA structure may provide much of the specificity for the interaction. PMID- 1899842 TI - Two distinct destabilizing elements in the c-fos message trigger deadenylation as a first step in rapid mRNA decay. AB - The mechanisms by which c-fos mRNA is targeted for decay have been examined. Rapid removal of the poly(A) tail occurs before the transcribed portion of the c fos message is degraded. Identification of the determinants that mediate c-fos message deadenylation reveals that they coincide directly with previously characterized determinants of c-fos mRNA instability, one in the protein-coding region and the other an AU-rich element (ARE) in the 3'-untranslated region. Insertion of either of these c-fos instability elements into the stable beta globin message confers the property of rapid deadenylation. Mutation of the ARE indicates that this sequence controls two steps in the process of c-fos mRNA degradation: removal of the poly(A) tail, which does not require intact AUUUA pentanucleotides within the ARE, and subsequent degradation of the transcribed portion of the message, which appears to be dependent on the AUUUA pentanucleotides. These results indicate that structurally distinct instability determinants within the transcribed portion of labile messages can function by promoting rapid removal of the poly(A) tail as a first step in the decay process. PMID- 1899843 TI - An arginine to lysine substitution in the bZIP domain of an opaque-2 mutant in maize abolishes specific DNA binding. AB - The opaque-2 (o2) locus in maize encodes a transcription factor involved in the regulation of zein storage proteins. We have shown previously that the O2 protein contains a leucine zipper domain that binds to promoters of 22-kD zein genes. In this paper we characterize an EMS-induced o2 allele, o2-676, that causes a 50% reduction in zein. We have found that the o2-676 mutant protein does not show specific recognition of zein promoter fragments because of the substitution of a lysine residue for an arginine residue within the bZIP domain of o2-676. This particular arginine is conserved within the bZIP domains of all mammalian, fungal, and plant DNA binding proteins of this class. The correlation between this mutation in o2 and the altered pattern of zein expression strongly suggests that O2 regulates transcription of certain members of the zein multigene family through direct interaction with the zein promoters and not through the transcriptional activation of some other regulator of zein gene expression. PMID- 1899844 TI - Escherichia-Pseudomonas shuttle vectors derived from pUC18/19. AB - Two new broad-host-range plasmid vectors, pUCP18 and pUCP19, which are stably maintained in Escherichia coli and Pseudomonas aeruginosa have been constructed. The plasmids are based on the E. coli pUC18 and pUC19 vectors and possess all their features: (i) convenient direct screening of recombinants; (ii) versatile multiple cloning site; (iii) use as sequencing and expression vectors; (iv) small size; and (v) intermediate to high copy number. PMID- 1899845 TI - The subtilisin Carlsberg pro-region is a membrane anchorage for two fusion proteins produced in Bacillus subtilis. AB - The extracellular serylprotease subtilisin Carlsberg (SubC) of Bacillus licheniformis is produced in a precursor form which includes a signal peptide (sp) and a pro-region. We have constructed a fusion protein in which the sp, pro region and 38 amino acids (aa) at the N terminus of SubC were joined to the immunoglobulin (Ig) G-binding protein G produced by group G streptococci. The fused SubC::protein G was purified on IgG-Sepharose. IgG-binding material derived from membrane or supernatant fractions had different N termini, indicating that release from the membrane occurred only after removal of the pro-region. The proteolytic pattern was identical when SubC::protein G was produced in Bacillus subtilis 168 wild type or in a protease-deficient strain. The sp cleavage point was also defined in the membrane-derived material. PMID- 1899846 TI - Sequence and expression of genes encoding the large and small subunits of ribulose 1,5-bisphosphate carboxylase/oxygenase from Chromatium vinosum. AB - A DNA fragment bearing genes for the large (rbcL) and small (rbcS) subunits of ribulose 1,5-bisphosphate carboxylase/oxygenase (RuBisCO) was cloned from the photosynthetic purple sulfur bacterium Chromatium vinosum. Enzymatically fully active RuBisCO was synthesized in Escherichia coli cells when the cloned DNA was placed downstream of tac promoter. Nucleotide (nt) sequences of rbcL-rbcS were more homologous to cyanobacterial counterparts than to those from Alcaligenes eutrophus or higher plants. However, the amino acid (aa) sequence in a domain responsible for CO2 activation in the C. vinosum rbcL product resembled the corresponding aa sequence in higher plant RuBisCos, but not in the cyanobacterial enzymes. Chemically determined aa sequences at the N terminals of both subunits of RuBisCO purified from C. vinosum were not identical to those deduced from the nt sequences, although they were completely the same as aa sequences deduced from rbcA-rbcB, another locus encoding RuBisCO in C. vinosum. Therefore, the rbcL-rbcS locus seems to be barely expressed under a standard condition for photoautotrophic growth. The homology of the nt sequences between rbcL and rbcA was 82%, and that between rbcS and rbcB was 63%, whereas the codon usages of these genes were basically identical. The rbcL-rbcS and rbcA-rbcB loci therefore must have evolved from a common ancestral set of genes after duplication, instead of lateral gene transfer. PMID- 1899847 TI - Cloning and analysis of the gene encoding the cytadherence phase-variable protein HMW3 from Mycoplasma pneumoniae. AB - We have cloned the gene encoding the Mycoplasma pneumoniae cytadherence-accessory protein HMW3 into Escherichia coli to study its phase-variable expression. A truncated HMW3 protein (HMW3'; 113 kDa), identified using HMW3-specific, affinity purified antibodies, was expressed under the control of the lacZ promoter in lambda gt11. The protein did not react with beta-galactosidase (beta Gal) specific antibodies, however, indicating that HMW3' was not a beta Gal fusion protein. The direction of transcription was determined by examining gene expression from inserts in opposite orientations with respect to the lacZpo in pUC18 and pUC19, to generate pKV5 and pKV6. Amino acid sequence data were obtained from an enzymatically generated HMW3 peptide fragment and used to create a degenerate 17-mer probe. The degenerate 17-mer hybridized to the mycoplasma DNA insert in pKV6; both the 17-mer and the pKV6 insert hybridized to a 9.4-kb EcoRI fragment from wild-type (wt) M. pneumoniae chromosomal DNA. This EcoRI fragment was cloned from wt M. pneumoniae and an HMW3-deficient variant in both orientations into pUC18. The HMW3'-encoding region was localized to the center of the 9.4-kb EcoRI fragment, and no differences were observed in restriction patterns between the wt and variant. Although the 9.4-kb EcoRI fragment included the DNA segment encoding HMW3', neither this protein, nor derivatives thereof, were detected in IPTG-induced E. coli containing the EcoRI fragment from either wt or variant M. pneumoniae, in either orientation in pUC18. PMID- 1899848 TI - A complex family of class-II restriction endonucleases, DsaI-VI, in Dactylococcopsis salina. AB - A series of class-II restriction endonucleases (ENases) was discovered in the halophilic, phototrophic, gas-vacuolated cyanobacterium Dactylococcopsis salina sp. nov. The six novel enzymes are characterized by the following recognition sequences and cut positions: 5'-C decreases CRYGG-3' (DsaI); 5'-GG decreases CC 3' (DsaII); 5'-R decreases GATCY-3' (DsaIII); 5'-G decreases GWCC-3' (DsaIV); 5' decreases CCNGG-3' (DsaV); and 5'-GTMKAC-3' (DsaVI), where W = A or T, M = A or C, K = G or T, and N = A, G, C or T. In addition, traces of further possible activity were detected. DsaI has a novel sequence specificity and DsaV is an isoschizomer of ScrFI, but with a novel cut specificity. A purification procedure was established to separate all six ENases, resulting in their isolation free of contaminating nuclease activities. DsaI cleavage is influenced by N6 methyladenine residues [derived from the Escherichia coli-encoded DNA methyltransferase (MTase) M.Eco damI] within the overlapping sequence, 5' CCRYMGGATC-3'; DsaV hydrolysis is inhibited by a C-5-methylcytosine residue in its recognition sequence (5'-CMCNGG-3'), generated in some DsaV sites by the E. coli-encoded MTase, M.Eco dcmI. PMID- 1899849 TI - Responsiveness to phenobarbital in an adult with Crigler-Najjar disease associated with neurological involvement and skin hyperextensibility. AB - We present the case of a 23-yr-old man who had had since birth marked and sustained unconjugated non-hemolytic hyperbilirubinemia and who had had several attacks of grand mal seizures. Analysis of serum bilirubin by diazoreactive methods showed serum levels of unconjugated bilirubin as high as 445 mumol/L that were not affected by phenobarbital administration. However, analysis of serum bile pigments by high-pressure liquid chromatography demonstrated marked decrease of unconjugated bilirubin after phenobarbital treatment (from 432.4 mumol/L to 291.0 mumol/L) associated with slight increase of bilirubin monoconjugates and disconjugates (from 0.25 mumol/L to 0.42 mumol/L). Furthermore, in the past few years the patient had exhibited striking skin hyperextensibility and diaphragm eventration. This case confirms that alkaline methanolysis-high-pressure liquid chromatography is the most reliable method for assessment of serum fraction bilirubin levels; that clinical parameters such as neurological signs do not unequivocally discriminate between type I and II Crigler-Najjar disease and that response to phenobarbital treatment remains the main diagnostic tool. PMID- 1899850 TI - Cholestasis and changes of portal pressure caused by chlorpromazine in the perfused rat liver. AB - Chlorpromazine (10 mumol/L) causes a marked increase in portal pressure in perfused rat liver. Simultaneously, oxygen consumption, hepatic clearance of taurocholate and bile flow are diminished. These effects are prevented by the cyclooxygenase inhibitors indomethacin (15 mumol/L), acetylsalicylate (3 mmol/L) or ibuprofen (200 mumol/L). On addition of chlorpromazine the liver releases increased amounts of prostaglandin D2; this increase does not occur in the presence of indomethacin. At higher concentrations of chlorpromazine (100 mumol/L) the inhibition of taurocholate clearance and bile flow is accompanied by only a moderate increase of portal pressure, and indomethacin is without effect. At this high concentration, substantial cell damage, as indicated by the release of lactate dehydrogenase, is present. We conclude that arachidonic acid-derived metabolites, notably prostanoids, are involved in the inhibition of bile flow and of taurocholate clearance observed at low concentrations of chlorpromazine. The data suggest that changes in the microcirculation are responsible for the impairment of the liver functions. At higher concentrations of chlorpromazine the cell toxicity of the drug becomes prominent. PMID- 1899851 TI - Ultrastructural localization of interferon-producing cells in the livers of patients with chronic hepatitis B. AB - Cells expressing alpha- and gamma-interferon were localized in the liver tissue of patients with chronic hepatitis B by means of light and electron microscopy using monoclonal antibodies. Interferon-positive cells were regularly seen in the infiltrating mononuclear cells, and the number showed a good correlation with the degree of the necroinflammatory activity of the disease. In chronic persistent hepatitis and in normal livers, they were infrequent or virtually absent. alpha Interferon was shown to be positive in lymphocytes, polymorphonuclear leukocytes and fibroblasts, Kupffer cells and, weakly, in the cytoplasm of a few hepatocytes in cases of active hepatitis, whereas gamma-interferon was demonstrated only in lymphocytes. The expression of human leukocyte class I antigens on hepatocytes showed a close association with the number of interferon-producing cells, but not with the presence of virus particles and HBcAg in liver cells, when studied using electron microscopy and double-labeling. Interferon seems to be an important regulator of the local immune response in the liver in patients with chronic hepatitis B. Its functions may play a role in inducing the human leukocyte class I antigen expression on hepatocytes, thus enhancing the elimination of virus containing hepatocytes by major histocompatibility complex-restricted cytotoxic lymphocytes. PMID- 1899852 TI - High doses of recombinant alpha-interferon or gamma-interferon for chronic hepatitis C: a randomized, controlled trial. AB - Chronic hepatitis C is often a progressive liver disease for which there is no satisfactory treatment. We studied the efficacy of recombinant alpha-interferon or gamma-interferon in the treatment of this disease in comparison with a control group. Thirty patients were randomly assigned to three groups. Ten patients received 7.5 MU alpha-interferon/m2 body surface three times weekly for 3 mo, then 5 MU/m2 for 3 mo and 2.5 MU/m2 for 6 mo. Ten patients were treated with gamma-interferon at a dose of 2 MU/m2 for 6 mo and the other 10 served as controls without treatment. The mean serum ALT levels and liver histological findings improved significantly only in the patients treated with alpha interferon. No changes were observed in patients treated with gamma-interferon or in controls. Five of 10 patients treated with alpha-interferon had complete responses (mean ALT normal during therapy). After treatment ALT returned to pretreatment levels in two of 5 patients. The long-term response rate after alpha interferon therapy was 30% at 18 mo. We conclude that alpha-interferon is effective in controlling disease activity in a portion of patients with chronic hepatitis C. High doses of alpha-interferon do not appear to add further benefit in the response rate or relapse rate. gamma-Interferon therapy is ineffective. PMID- 1899854 TI - Aberrant expression of HLA class-I antigens in Burkitt lymphoma cells. AB - HLA class-I expression has been investigated by biochemical methods in 14 Burkitt lymphoma (BL) cell lines and the corresponding Epstein-Barr virus (EBV) transformed lymphoblastoid cell lines (LCL) derived from the same individuals. Selective down-regulation of one or more HLA class-I specificities was demonstrated in 9 out of 14 BL lines. The defect was restricted to a single HLA-A allele in 3 of the lines (BL29, BL72, WW-I-BL). Four lines (BL28, BL37, BL41 and Jijoye M13) showed down-regulation of both HLA-A and -C alleles, and one (BL36) failed to express one HLA-C allele. Only one BL line (WW-2-BL) had lost one HLA-A and one HLA-B allele. The allele-specific defects were mainly detected in cell lines that had maintained the phenotypic characteristics of the original tumor. Expression of B-cell activation markers and the EBV-encoded nuclear antigen (EBNA)-2 correlated with up-regulation of the Cw4 allele in the P79 subline of the BL line Jijoye. Treatment with gamma-interferon (IFN) resulted in full or partial reversion of the HLA class-I defects in some of the cases but had no significant effect in others. This was not due to a cell-line-related unresponsiveness to IFN, nor did it reflect an allele-specific mode of regulation because the same allele could respond differently in different cell lines. The data suggest that defective expression of HLA class-I antigens, which appears to be more prevalent for alleles within the HLA-A and -C loci, is a common feature of BL cell lines. Different regulatory mechanisms appear to be involved. PMID- 1899853 TI - Evolutionary relationship between human and mouse immunoglobulin kappa light chain variable region genes. AB - Similar to the Igh-V multigene family, the human or mouse Igk-V repertoire is a distorted continuum of homologous genes that may be grouped into families displaying greater than 80% nucleic acid sequence similarity among their members. Systematic interspecies sequence comparisons reveal that most human Igk-V gene families exhibit clear homology to mouse Igk-V families (sequence similarity generally greater than 74%). A hypothetical phylogenetic tree of Igk-V genes predicts that a minimum of seven Igk-V genes/families predate mammalian radiation. In two cases, several interrelated mouse Igk-V families exhibit phylogenetic equidistance with just one human Igk-V family, implying a more pronounced divergence for the elevated number of Igk-V gene families in the mouse. Mouse-human Igk-V comparisons, moreover, illustrate how expansion, contraction, and perhaps deletion of Igk-V gene families shape the Igk-V repertoire during mammalian evolution. PMID- 1899855 TI - A management approach to incompletely excised basal cell carcinomas of skin. AB - There were 187 incompletely resected basal cell carcinomas (BCC) of skin referred to the Princess Margaret Hospital between 1970 and 1985. Median age at presentation was 62 years. The commonest location of these lesions was in the head and neck region (93%). One hundred twenty lesions were immediately treated: 119 were irradiated and 1 was excised. The remaining 67 lesions were managed expectantly. Follow-up time for the entire population ranged from 1 month to 17 years, with a median time of 2.7 years. The 5-year probability of remaining relapse-free in the group immediately treated was 91% versus 61% if managed expectantly (p = 0.0001). If only lateral margins were positive, the crude probability of local failure was 3/18 (17%), versus 9/27 (33%) if the deep margins were involved (p = 0.2). Once relapse occurred in the group of lesions treated expectantly, 17/20 (85%) of these relapses were salvaged by either radiation or surgery. The 10-year actuarial probability of local control for the lesions immediately treated and observed were similar: 92% and 90%, respectively (p = 0.5). An economic analysis revealed that immediate radiation treatment saved the health system only $223.00 per patient. Since there is no difference in the ultimate local control between these two approaches, and these elderly patients may be spared the morbidity of unnecessary treatments, it is suggested that a policy of observation may be adopted for basal cell carcinomas of skin which have been incompletely excised. PMID- 1899856 TI - Heterogeneity of heat response in murine, canine and human tumors: influence on predictive assays. AB - The heterogeneity of response to hyperthermia of cells taken from different regions of tumors was tested in a model tumor system (RIF-1) in the mouse and in specimens from spontaneous tumors taken from dogs and humans at the time of surgical resection. Cell survival was assayed by clonogenic survival in the murine tumor and by dansyl lysine staining in tumors from all three species. Using survival as an endpoint, it was found that the extent of heterogeneity depended on the temperature to which the tumor was heated and the duration of exposure. By increasing either of these factors, the coefficient of variation was increased. The large heterogeneity seen after in vivo heating could not be explained entirely by inhomogeneous heating within the tumor as evidenced by temperature mapping. It is concluded that other microenvironmental factors such as blood flow, pH, O2, and nutrient supply may cause variations in the heat response of the tumor cells in vivo. Little, if any, evidence of cellular heterogeneity was evident for all three species when comparisons were made between samples of 100-200 mg. The canine and human tumors were considerably more heat resistant when dansyl lysine was used as an endpoint. In the RIF-1 tumors, heterogeneity of heat response was greater after in vitro heating than after in vivo heating when small biopsy samples (10-20 mg) were taken, suggesting that some cellular heterogeneity was present. PMID- 1899857 TI - Neurologic manifestations of trypanosomiasis in a dog. AB - A 13-month-old Doberman Pinscher was evaluated because of slowly progressive paraparesis and signs of depression. The dog had temporal, supraspinatus, and infraspinatus muscle atrophy, bilateral enophthalmos, superficial inguinal lymphadenopathy, tachycardia with pulse deficits, and lesions of active and inactive chorioretinitis. Neurologic abnormalities included hyperreflexic patellar reflexes, lack of conscious proprioception, signs of superficial pain in the hind limbs, and depressed hopping reflexes in the forelimbs. Cranial nerve abnormalities included decreased sensation in the left nostril and a delayed gag reflex. Results of cerebrospinal fluid analysis were characteristic of nonsuppurative inflammation. A diagnosis of multifocal neurologic disease was made. The dog did not have serum titers for fungal diseases, canine distemper, Ehrlichia canis infection, borreliosis, Rocky Mountain spotted fever, or toxoplasmosis. The dog did not respond to various antimicrobial treatments, and only slightly responded to corticosteroid treatment. The dog died during an anesthetic procedure. The postmortem diagnosis of Trypanosoma cruzi infection (canine Chagas disease) was made on identification of the amastigote form of the organism in sections of brain, spinal cord, and myocardium. PMID- 1899858 TI - The spo0K locus of Bacillus subtilis is homologous to the oligopeptide permease locus and is required for sporulation and competence. AB - Spore formation in Bacillus subtilis is a dramatic response to environmental signals that is controlled in part by a two-component regulatory system composed of a histidine protein kinase (SpoIIJ) and a transcriptional regulator (Spo0A). The spo0K locus plays an important but undefined role in the initiation of sporulation and in the development of genetic competence. spoIIJ spo0K double mutants had a more severe defect in sporulation than either single mutant. Overproduction of the spoIIJ gene product resulted in the suppression of the sporulation defect, but not the competence defect, caused by mutations in the spo0K locus. On the basis of the phenotype of the spoIIJ spo0K double mutant and the effect of overproduction of the spoIIJ gene product, a transposon insertion in the spo0K locus was isolated. The spo0K locus was cloned and sequenced. spo0K proved to be an operon of five genes that is homologous to the oligopeptide permease (opp) operon of Salmonella typhimurium and related to a large family of membrane transport systems. The requirement for the transport system encoded by spo0K in the development of competence was somewhat different than its requirement in the system encoded by spo0K in the development of competence was somewhat different than its requirement in the initiation of sporulation. Disruption of the last open reading frame in the spo0K operon caused a defect in competence but had little or no effect on sporulation. We hypothesize that the transport system encoded by spo0K may have a role in sensing extracellular peptide factors that we have shown are required for efficient sporulation and perhaps in sensing similar factors that may be necessary for genetic competence. PMID- 1899859 TI - Pseudomonas aeruginosa AlgB, a two-component response regulator of the NtrC family, is required for algD transcription. AB - Most strains of Pseudomonas aeruginosa isolated from the respiratory tracts of cystic fibrosis patients have a mucoid colony morphology due to the synthesis of an expolysaccharide called alginate. The algB gene product (AlgB) is necessary for the high-level production of alginate in mucoid P. aeruginosa. In this study, AlgB was shown to be involved in the transcription of algD, a gene previously demonstrated to be activated in mucoid P. aeruginosa. In vitro and in vivo expression studies reveal that algB encodes a protein with a molecular size of 49 kDa. The DNA sequence of a 2.2-kb P. aeruginosa fragment containing algB was also determined. The amino-terminal domain of AlgB was found to be conserved with the amino-terminal domains of the response regulator class of two-component regulatory proteins. The central domain of AlgB has sequences highly conserved with those in the NtrC subfamily of transcriptional activators (NtrC, NifA, HydG, DctD, FlbD, TyrR, and PgtA). The central domain of AlgB also contains a potential nucleotide binding site. AlgB is the first NtrC homolog described from P. aeruginosa. At the carboxy terminus of AlgB, a helix-turn-helix motif was observed, suggesting that AlgB is a DNA-binding protein. The strongly conserved NtrC-like central domain of AlgB is not present in AlgR, another alginate response regulator. This study therefore identifies and characterizes the second of at least two unique response regulators used by P. aeruginosa to control alginate gene expression. PMID- 1899860 TI - Purification and characterization of NADP(+)-dependent 5,10 methylenetetrahydrofolate dehydrogenase from Peptostreptococcus productus marburg. AB - The 5,10-methylenetetrahydrofolate dehydrogenase of heterotrophically grown Peptostreptococcus productus Marburg was purified to apparent homogeneity. The purified enzyme catalyzed the reversible oxidation of methylenetetrahydrofolate with NADP+ as the electron acceptor at a specific activity of 627 U/mg of protein. The Km values for methylenetetrahydrofolate and for NADP+ were 27 and 113 microM, respectively. The enzyme, which lacked 5,10-methenyltetrahydrofolate cyclohydrolase activity, was insensitive to oxygen and was thermolabile at temperatures above 40 degrees C. The apparent molecular mass of the enzyme was estimated by gel filtration to be 66 kDa. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed the presence of a single subunit of 34 kDa, accounting for a dimeric alpha 2 structure of the enzyme. Kinetic studies on the initial reaction velocities with different concentrations of both substrates in the absence and presence of NADPH as the reaction product were interpreted to indicate that the enzyme followed a sequential reaction mechanism. After gentle ultracentrifugation of crude extracts, the enzyme was recovered to greater than 95% in the soluble (supernatant) fraction. Sodium (10 microM to 10 mM) had no effect on enzymatic activity. The data were taken to indicate that the enzyme was similar to the methylenetetrahydrofolate dehydrogenases of other homoacetogenic bacteria and that the enzyme is not involved in energy conservation of P. productus. PMID- 1899862 TI - Probing the role of lysines and arginines in the catalytic function of cytochrome P450d by site-directed mutagenesis. Interaction with NADPH-cytochrome P450 reductase. AB - To identify amino acids of cytochrome P450d (P450d) which participate in the interaction with NADPH-cytochrome P450 reductase, we changed conserved ionic amino acids of P450d to others by site-directed mutagenesis. Turnover numbers (0.032-0.008 min-1) of purified mutants Lys94-Glu, Lys99-Glu, Lys105-Glu, Lys440 Glu, Lys453-Glu, Arg455-Glu, and Lys463-Glu toward 7-ethoxycoumarin were much lower than that (0.380 min-1) of the wild type at 25 degrees C. Reduction rates (less than 0.054 s-1) of the heme of all mutants (0.1 microM) in the presence of NADPH and the reductase (0.3 microM) were much lower than that (5.9 s-1) of the wild type. Furthermore, a turnover number (0.042 min-1) of a microsomal triple mutant (Arg135-Leu + Arg136-Leu + Arg137-Leu) of a conserved Arg cluster was much lower than that (0.674 min-1) of the wild type at 37 degrees C. Thus, we suggest that Lys94, Lys99, Lys105, Lys440, Lys453, Arg455, Lys463, and perhaps the Arg cluster Arg135-Arg136-Arg137 of P450d will participate in the intermolecular electron transfer process by forming ionic bridges between the two proteins and/or by orienting appropriate geometry for electron transfer on the interfacial surface between the two proteins. PMID- 1899861 TI - Reduction of ribonucleotides by the obligate intracytoplasmic bacterium Rickettsia prowazekii. AB - Rickettsia prowazekii, an obligate intracellular parasitic bacterium, was shown to have a ribonucleotide reductase that would allow the rickettsiae to obtain the deoxyribonucleotides needed for DNA synthesis from rickettsial ribonucleotides rather than from transport. In the presence of hydroxyurea, R. prowazekii failed to grow in mouse L929 cells or SC2 cells (a hydroxyurea-resistant cell line), which suggested that R. prowazekii contains a functional ribonucleotide reductase. This enzymatic activity was demonstrated by the conversion of ADP to dADP and CDP to dCDP, using (i) a crude extract of Renografin-purified R. prowazekii that had been harvested from infected yolk sacs and (ii) high performance liquid chromatographic analysis. The rickettsial ribonucleotide reductase utilized ribonucleoside diphosphates as substrates, required magnesium and a reducing agent, and was inhibited by hydroxyurea. ADP reduction was stimulated by dGTP and inhibited by dATP. CDP reduction was stimulated by ATP and adenylylimido-diphosphate and inhibited by dATP and dGTP. These characteristics provided strong evidence that the rickettsial enzyme is a nonheme iron-containing enzyme similar to those found in mammalian cells and aerobic Escherichia coli. PMID- 1899863 TI - 19F and 31P NMR spectroscopy of G protein alpha subunits. Mechanism of activation by Al3+ and F-. AB - 19F and 31P NMR spectroscopy was used to study the mechanism of activation of the alpha subunits of guanine nucleotide-binding regulatory proteins (G proteins) by Al3+, Mg2+, and F-. 19F NMR spectra of solutions containing Al3+, Mg2+, and F- showed a characteristic F- peak at -10 ppm. Addition of the GDP-bound form of either of two G protein alpha subunits (G alpha) resulted in the appearance of an additional peak at -29 or -30 ppm. This peak was not observed with guanosine 5'-3 O-(thio)triphosphate-G alpha or with GDP alone. Titration of Al3+, Mg2+, and F- indicated that each molecule of G alpha binds 3-5 molecules of F- (Kd = 0.47 mM), a single molecule of Al3+ (Kd much less than 0.1 mM), and a single Mg2+ ion (Kd about 0.1 mM). Replacement of Mg2+ with Mn2+ caused a dramatic broadening of the NMR signal, indicating that the metal ion binds in proximity to the protein-bound F- (less than 1 nm). 31P NMR of GDP-G alpha showed peaks at -2 and -8.6 ppm, corresponding to the beta- and alpha-phosphoryl groups of GDP, respectively. Binding of Al3+, Mg2+, and F- caused an upfield shift of 6 ppm for the beta phosphoryl signal with no change in the alpha-phosphoryl signal. These observations indicate that Mg2+.GDP.AlF3-5 mimics Mg2+.GTP in its capacity to activate G protein alpha subunits. PMID- 1899864 TI - Interferon-gamma-inducible regulation of the human invariant chain gene. AB - Interferon-gamma (IFN-gamma) regulates a variety of immunoregulatory functions through the induction of a specific set of IFN-gamma response genes. This includes the invariant chain associated with the major histocompatibility complex class II molecules. To investigate the mechanism involved in the invariant chain (In) response to IFN-gamma we constructed chloramphenicol acetyltransferase (CAT) hybrid genes in which the CAT gene is under the control of the In promoter. The glioblastoma cell line, U-373 MG, transfected with a CAT construct having the In promoter sequence -790 to +1 bp showed over 3-fold increased CAT activity when treated with IFN-gamma indicating that this region confers IFN-gamma responsiveness to the CAT gene. The IFN-gamma response element in the promoter was further sublocalized to the region -120 to -61 base pairs (bp). This region contains homology to the interferon-stimulated response elements identified in other IFN responsive genes. By gel shift analyses, an IFN-gamma-induced sequence specific DNA-binding factor was identified. This induced complex binds to an oligonucleotide corresponding to -107 to -79 bp of the In promoter. Mutations of this binding site at -94 and -92 bp drastically decreased binding of the constitutive and IFN-gamma-induced complexes. This IFN-gamma induced factor also binds to an oligonucleotide corresponding to -91 to -62 bp of the interferon-beta (IFN-beta) gene promoter, a region necessary for the induction of the IFN-beta gene by virus and double-stranded RNA. This binding specificity is characteristic of a family of DNA binding factors that bind both the interferon-stimulated response elements and the IFN-beta gene promoter. PMID- 1899865 TI - Enhanced 2-deoxy-D-glucose uptake and metabolism in splenocytes from diabetic and diabetes-prone BB rats. Further evidence to support prior in vivo activation. AB - Glucose metabolism in splenocytes from the BB rat was studied for the presence of abnormalities in [14C] 2-deoxy-D-glucose (2-dGlc) uptake, [U-14C]glucose conversion to 14CO2, and the production of lactate and pyruvate. Cells were studied freshly isolated ("resting"), and following culture both unstimulated (control) and stimulated with concanavalin A (ConA) or phorbol myristate acetate (PMA) + ionomycin. Both resting and control cells from diabetic (BBd) and diabetes-prone (BBdp) rats transported more (p less than 0.05) 2-dGlc than did cells from nondiabetes-prone (BBn) rats. Consistent with prior in vivo activation, sustained in vitro, lactate production was higher (p less than 0.05) under control conditions in BBd and BBdp than in BBn cells. Lactate production increased less with ConA and PMA + ionomycin in both BBd and BBdp than in BBn cells. PMA + ionomycin increased 2-dGlc uptake as much in BBd and BBdp cells as in BBn cells. Elevated rates of pyruvate production were observed in BBd cells under resting, control, and (especially) ConA conditions, suggesting an abnormality in pyruvate conversion to lactate. Few changes were observed in 14CO2 production. The presence of similar abnormalities in BBdp cells to those of the BBd cells suggests that the diabetic state is not causal, and the absence of an in vitro effect of 15 mmol/liter glucose in BBn cells further tends to exclude hyperglycemia as a cause of these alterations. PMID- 1899866 TI - Overexpression of the relA gene in Escherichia coli. AB - Intracellular levels of guanosine 3',5'-bispyrophosphate (ppGpp) governed by the relA gene are normally regulated by aminoacyl-tRNA availability for protein synthesis. An experimental system is described in which cellular levels of ppGpp are controlled instead by induction of plasmid pKK223-3 derivatives with the relA structural gene, or portions thereof, under control of the Ptac promoter. In amino acid-rich media, isopropyl-1-thio-beta-D-galactopyranoside induction of transcription of the wild type relA gene in pSM10 yields about a 100-fold overexpression of a metabolically stable, full length (743 amino acid) RelA protein to levels approximating the number of cellular ribosomes. This overexpression is accompanied by a roughly parallel and relC-dependent elevation of ppGpp levels. Induction of a relA gene deletion mutant in pSM11 containing 455 amino-terminal amino acids results in much lower levels of expression of a metabolically unstable 55-kDa protein and elevated ppGpp levels that are almost equivalent to induced pSM10 and are relC-independent. Induction of a larger deletion in pSM12 containing 331 amino-terminal amino acids does not provoke ppGpp accumulation. We are able to elicit high levels of ppGpp without changing nutritional abundance and without massive overexpression of the RelA protein by inducing the metabolically unstable, truncated RelA protein. We find the effects of elevated ppGpp levels to include a slowing of growth, an inhibition of stable RNA accumulation, an inhibition of cellular rrn P1 promoter activities as measured by primer extension, and changes in the pattern of gene expression viewed by two-dimensional electrophoresis of cellular proteins. PMID- 1899867 TI - Endogenous non-cyclooxygenase metabolites of arachidonic acid modulate growth and mRNA levels of immediate-early response genes in rat mesangial cells. AB - The role of endogenous arachidonic acid and its metabolites as mediators of cell growth was studied in rat mesangial cells. Inhibitors of the cytochrome P450 monooxygenase and lipoxygenase systems (nordihydroguaiaretic acid (NDGA), SK&F 525A, and ketoconazole) significantly reduced serum-stimulated cell growth as determined by cell counts and incorporation of [3H]thymidine. Inhibition of cyclooxygenase or lipoxygenases alone had no effect on cell growth. Stimulation with arginine vasopressin, epidermal growth factor, or phorbol myristate acetate increased [3H]thymidine incorporation and mRNA levels of the immediate-early response genes c-fos and Egr-1. These increases in [3H]thymidine incorporation and mRNA levels were reduced by NDGA and ketoconazole. NDGA, SK&F 525A, and ketoconazole had no effect on cellular ATP levels. Indomethacin had no effect upon cell growth. 14,15-Epoxyeicosatrienoic acid potentiated the effect of arginine vasopressin to enhance [3H]thymidine incorporation. Reverse-phase high pressure liquid chromatography analysis of lipid extracts from cells prelabeled with [3H]arachidonic acid resulted in the detection of a radioactive peak which eluted with lipoxygenase and monooxygenase products, with the same retention time as vicinal dihydroxyeicosatrienoic acids. This peak increased after stimulation with arginine vasopressin or epidermal growth factor and was reduced by preincubation with NDGA. Furthermore, analysis of unlabeled cell extracts by gas chromatography-mass spectrometry revealed the presence of a compound with epoxyeicosatrienoic acid-like characteristics. These results indicate that mesangial cells in culture likely produce products of the cytochrome P450 monooxygenase system that are important endogenous mediators of the growth response to mitogenic agents. PMID- 1899868 TI - Structural and functional studies of cross-linked Go protein subunits. AB - The guanine nucleotide binding proteins (G proteins) that couple hormone and other receptors to a variety of intracellular effector enzymes and ion channels are heterotrimers of alpha, beta, and gamma subunits. One way to study the interfaces between subunits is to analyze the consequences of chemically cross linking them. We have used 1,6-bismaleimidohexane (BMH), a homobifunctional cross linking reagent that reacts with sulfhydryl groups, to cross-link alpha to beta subunits of Go and Gi-1. Two cross-linked products are formed from each G protein with apparent molecular masses of 140 and 122 kDa on sodium dodecyl sulfate polyacrylamide gel electrophoresis. Both bands formed from Go reacted with anti alpha o and anti-beta antibody. The mobility on sodium dodecyl sulfate polyacrylamide gel electrophoresis is anomalous since the undenatured, cross linked proteins have the same Stokes radius as the native, uncross-linked alpha beta gamma heterotrimer. Therefore, each cross-linked product contains one alpha and one beta subunit. Activation of Go by guanosine 5'-3-O-(thio)triphosphate (GTP gamma S) does not prevent cross-linking of alpha to beta gamma, consistent with an equilibrium between associated and dissociated subunits even in the presence of GTP gamma S. The same cross-linked products of Go are formed in brain membranes reacted with BMH as are formed in solution, indicating that the residues cross-linked by BMH in the pure protein are accessible when Go is membrane bound. Analysis of tryptic peptides formed from the cross-linked products indicates that the alpha subunit is cross-linked to the 26-kDa carboxyl terminal portion of the beta subunit. The cross-linked G protein is functional, and its alpha subunit can change conformation upon binding GTP gamma S. GTP gamma S stabilizes alpha o to digestion by trypsin (Winslow, J.W., Van Amsterdam, J.R., and Neer, E.J. (1986) J. Biol. Chem. 261, 7571-7579) and also stabilizes the alpha subunit in the cross-linked product. Cross-linked G o can be ADP ribosylated by pertussis toxin. This ADP-ribosylation is inhibited by GTP gamma S with a concentration dependence that is indistinguishable from that of the control, uncross-linked G o. These two kinds of experiments indicate that alpha o is able to change its conformation even though it cannot separate completely from beta gamma. Thus, although dissociation of the subunits accompanies activation of G o in solution, it is not obligatory for a conformational change to occur in the alpha subunit. PMID- 1899869 TI - Nuclear targeting of prothymosin alpha. AB - Prothymosin alpha is a highly acidic protein which lacks an amino-terminal signal peptide, yet was once thought to be a precursor for thymosin alpha 1, a putative peptide hormone secreted by the thymus. Here, two lines of evidence are presented that strongly implicate prothymosin alpha as a nuclear protein: 1) in COS cells transfected with the human prothymosin alpha gene copious amounts of prothymosin alpha were present in sealed nuclei obtained by treating these cells with cytochalasin B and enucleating them centrifugally. 2) Constructs in which human prothymosin alpha nucleic acid sequences were fused in-frame either near the amino terminus of the beta-galactosidase gene in pCH110 or at the carboxyl terminus, when expressed in COS cells, resulted in nuclear localization of the fusion protein; indirect immunofluorescence in situ was used as the assay. The basic cluster of amino acids at the carboxyl terminus of prothymosin alpha, TKKQKT, has been identified as part of the nuclear targeting signal, whereas the basic cluster of amino acids situated within the thymosin alpha 1 sequence at the amino terminus failed to effect nuclear transport. PMID- 1899870 TI - CD8+ high CD11b+ low T cells (T suppressor-effectors) in multiple sclerosis cerebrospinal fluid are increased during high dose corticosteroid treatment. AB - Using simultaneous dual direct immunofluorescence the effect of high dose intravenous methylprednisolone on the expression of T lymphocyte differentiation antigens in paired cerebrospinal fluid and peripheral blood samples of nine clinically active patients with multiple sclerosis was studied. Corticosteroid treatment was associated with a clinical improvement in eight out of the nine patients. In cerebrospinal fluid of all patients the treatment was associated with a decrease of CD3+, CD4+ and CD8+ T cells, and of intra-central nervous system IgG synthesis. CD8+ high CD11b+ low suppressor-effector T cells behaved differently in the eight patients who improved with treatment, where they significantly increased, and in the patient without clinical response, where they were almost unchanged. Similar phenotypic changes were found in peripheral blood, and all changes returned towards baseline after treatment. The lower sensitivity to corticosteroids of CD8+ high CD11b+ low T cells could change the balance between immunoregulatory T subsets. In this study the increased availability of a subpopulation mainly composed of T cells with a suppressor-effector function was associated with a clinical response to treatment. PMID- 1899871 TI - Identification of an interferon-gamma-responsive element of a class II major histocompatibility gene in rat type 1 astrocytes. AB - Interferon-gamma(IFN-gamma) has been shown to induce class II major histocompatibility complex (MHC) antigens on several cell types. Previous analysis of cell lines including a glioblastoma multiforme line by our laboratory has mapped an IFN-gamma-responsive element to the upstream - 141 to - 109 base pair (bp) region of the DRA promoter. Using deletion mutants, this report shows that this same general region (-135 to -109 bp) is important for IFN-gamma induction in two other human glioma lines and more importantly in primary astrocytes. We have confirmed that this regulatory region of the HLA-DRA gene is necessary for IFN-gamma inducibility in astrocytes using a substitution mutant. Sequences beyond -135 bp do not appear to have any additional positive or negative elements. PMID- 1899872 TI - An ELISA for the detection of chimeric and human antibodies that contain kappa light chains in nonhuman primate serum. PMID- 1899873 TI - Synergistic effect of human lysozyme plus ampicillin or beta-lysin on the killing of Listeria monocytogenes. AB - Although ampicillin is often only bacteriostatic for Listeria monocytogenes in vitro, serum from ampicillin-treated patients was bactericidal. The bactericidal effect of serum was partly removed by bentonite, Seitz-filtration, and addition of FeCl3, suggesting it is mediated by lysozyme and beta-lysin. Partly purified human beta-lysin plus purified human lysozyme or either protein plus ampicillin were bactericidal for L. monocytogenes. Hen egg white lysozyme was not active. Lysozyme and beta-lysin were not synergistic with tetracycline, trimethoprim/sulfamethoxazole, or chloramphenicol. Thus, lysozyme and beta-lysin may play a role in the natural resistance to L. monocytogenes, and these serum proteins could contribute to the effectiveness of ampicillin in vivo. PMID- 1899874 TI - Interaction of cytokines and alveolar cells with Pneumocystis carinii in vitro. AB - Although deficient cellular immune function is a major predisposing factor in the development of Pneumocystis carinii pneumonia, the mechanisms involved in cellular immune surveillance against P. carinii have not been defined. When P. carinii were separated from rat cells by a semipermeable membrane, alveolar macrophages secreted substances lethal to P. carinii only when the macrophages were activated by interferon-gamma; normal macrophages were ineffective. Type II alveolar epithelial cells caused death of P. carinii whether or not interferon gamma was present. The effects of soluble mediators also were tested; recombinant human tumor necrosis factor-alpha (TNF) but not recombinant rat interferon-gamma or endotoxin was directly lethal to P. carinii. These lethal effects were prevented when antiserum to TNF or antioxidants (catalase and superoxide dismutase) were included. These data suggest that TNF may be a major mediator involved in the killing activity of activated macrophages against P. carinii and that TNF's activity against P. carinii is related to induction of oxidative stresses. PMID- 1899875 TI - Response to chemotherapy in experimental visceral leishmaniasis: T cell-dependent but interferon-gamma- and interleukin-2-independent. AB - The capacity of Leishmania donovani-infected BALB/c mice to respond to conventional chemotherapy with pentavalent antimony (Sb) is T cell dependent and, in nude mice, can be restored in part by treatment with the T cell lymphokines, interferon-gamma (IFN-gamma) or interleukin-2 (IL-2). To document the presumed role of endogenous IFN-gamma and IL-2 in responsiveness to antileishmanial chemotherapy in the T cell-intact host, L. donovani-infected euthymic BALB/c mice were treated with anti-IFN-gamma or anti-IL-2 monoclonal antibodies (MAbs) before and after Sb administration. Treatment with MAbs exacerbated visceral infection but did not inhibit the in vivo efficacy of Sb. Thus, while combination therapy of Sb plus IFN-gamma or IL-2 may prove beneficial in T cell-deficient hosts with visceral leishmaniasis, T cell activities other than or in addition to IFN-gamma or IL-2 production may mediate in vivo responsiveness to antileishmanial chemotherapy in the euthymic host. PMID- 1899876 TI - Detection of Mycobacterium tuberculosis antigen 5 in cerebrospinal fluid by inhibition ELISA and its diagnostic potential in tuberculous meningitis. AB - Inhibition ELISA was used to quantitate Mycobacterium tuberculosis antigen 5 in cerebrospinal fluid (CSF) specimens of 40 patients with a clinical diagnosis of tuberculous meningitis. In all 10 culture-proven patients, the assay was positive; in 30 culture-negative patients, the assay yielded positive results for 21. CSF antigen 5 concentrations ranged from 9 to 82 ng/ml (mean +/- SD, 45.5 +/- 6.2). In 40 patients with nontuberculous neurologic diseases, mean concentration was 1.45 ng/ml. Thus, inhibition ELISA for the detection of M. tuberculosis antigen 5 in CSF has definite diagnostic potential during the active phase of the disease and should be a routine diagnostic test, particularly when bacteriologic cultures in CSF are negative for M. tuberculosis. PMID- 1899877 TI - New serologic tests for early detection of coccidioidomycosis. AB - Arizona college students suspected of having recently acquired coccidioidomycosis were tested for anticoccidioidal antibodies and circulating fungal antigens using conventional antibody detection methods and new ELISA procedures. Of 233 patients with compatible symptoms, 26 had anticoccidioidal antibodies detected by conventional tests. ELISA detected antibodies in sera from 20 of these patients and also from another 25 patients. Patients with antibodies detected by either conventional or ELISA procedures were significantly more likely to have abnormal chest radiographs, elevated erythrocyte sedimentation rates, or absent upper respiratory symptoms than were other patients. Circulating antigen was found in sera from 35 patients, 33 of whom had no detectable anticoccidioidal antibodies at that time. Detectable antigen was noted frequently in sera obtained within the first month after the onset of symptoms and was infrequently detected later when more patients exhibited antibodies. These results indicate the feasibility of developing ELISA procedures using spherule-derived antigens for earlier detection of coccidioidal infections. PMID- 1899878 TI - Rh blood group and recurrent urinary tract infection. PMID- 1899880 TI - Two IgM paraproteins bearing cryoglobulin and anti-smooth muscle activities in a patient with Waldenstrom's macroglobulinaemia. AB - A 52-year-old white male subject with typical clinical and laboratory findings of Waldenstrom's macroglobulinaemia is described. Two paraprotein peaks of IgM lambda class, with different physical and chemical properties and different amino acid compositions, in both heavy and light chains, were found in the patient's serum. One of the IgM components (M1) was a cryoglobulin, and the other (M2) showed strong antismooth muscle activity. As far as we know, this is the first report of double paraproteins each of which has different properties. PMID- 1899879 TI - Assessment of hypothalamic-pituitary function in patients with familial amyloidotic polyneuropathy. AB - This study was performed to evaluate hypothalamic-pituitary hormone regulation in patients with familial amyloidotic polyneuropathy. Twenty-two patients without clinically overt endocrinological dysfunction were studied. A thyrotropin releasing hormone test revealed abnormal growth hormone regulation in 9 of 17 (53%) patients, and abnormal prolactin regulation in 9 of 18 (50%) patients. Abnormalities in either growth hormone or prolactin regulation were found in 12 of 17 (71%) patients. Serum somatomedin C levels were normal in all 22 patients. In 3 of 18 (17%) patients the plasma arginine vasopressin levels were low relative to the serum osmolality levels. Thus abnormalities in hypothalamic pituitary hormone regulation may be common in familial amyloidotic polyneuropathy. PMID- 1899881 TI - Rhythmic bacterial susceptibility to antibiotics at a large hospital. AB - The in vitro susceptibility response of Staphylococcus aureus, Klebsiella pneumoniae, Escherichia coli, Proteus mirabilis and Pseudomonas aeruginosa to a set of antibiotics was investigated in a survey comprising 19,380 positive cultures over a period of 5 years in a large hospital environment. Four out of the five species (P. aeruginosa being the exception) presented a species specific, drug-independent, rhythmic variation of their level of susceptibility to several antibiotics over the time of the study. The species-specific rhythmic responses were further characterized by spectral analysis, autocorrelation and cross-correlation functions. Through this analysis it was possible to rank the species according to their main period of oscillation. The longest period of oscillation was detected for S. aureus (38 months). K. pneumoniae and E. coli presented intermediate values (25 and 23 months respectively), and P. mirabilis the shortest period of oscillation (11 months). Species displaying long periods of oscillation tended to present very low levels of susceptibility, while species displaying short periods of oscillation usually presented the highest levels of susceptibility observed. Although some hospital environmental factors, such as drug consumption, were also analyzed, no correlation was found between them and the in vitro bacterial cyclic responses to antibiotics. PMID- 1899882 TI - For those left behind. An educational inpatient rehabilitation program. AB - 1. An interdisciplinary program model was developed for the treatment of mentally ill individuals remaining in long-term state mental institutions that focused on self-maintenance, social functioning, and community living skills. 2. Patients were categorized according to their levels of functioning and diagnoses, and were assigned to programs that were developed to meet the needs of a specific group of patients. 3. The goals of the program were to enhance the quality of life for the patients; promote self-direction and capacity for self-care by increasing the patient's opportunities to make life decisions; and prepare the patients to live in a less restrictive environment. PMID- 1899883 TI - Episodic secretion of gonadotrophins and ovarian steroids in jugular and utero ovarian vein plasma during the follicular phase of the oestrous cycle in gilts. AB - Blood samples were collected simultaneously from the jugular and utero-ovarian veins of 13 gilts from Days 11 through 16 of the oestrous cycle. A luteolytic dose (10 mg) of PGF-2 alpha was given on Day 12 to facilitate the natural occurrence of luteolysis and standardize the associated decrease in concentrations of progesterone. The mean interval from PGF to oestrus was 5.5 +/- 0.7 days (mean oestrous cycle length = 17.5 +/- 0.7 days). Mean concentrations, pulse amplitudes and pulse frequencies of oestradiol and progesterone were greater (P less than 0.05) in the utero-ovarian than jugular vein. Secretory profiles of LH and FSH were similar (P greater than 0.05) in plasma collected simultaneously from both veins. Based on these data, temporal relationships among hormonal patterns of FSH and LH in the jugular vein and oestradiol and progesterone in the utero-ovarian vein were examined. Concentrations of progesterone declined (P less than 0.05) between Days 12 and 14, while all secretory variables for oestradiol increased (P less than 0.05) from Day 12 through 16 of the oestrous cycle. The pulsatile secretion of FSH remained relatively constant during the experiment. However, both pulse amplitude and mean concentration tended (P less than 0.2) to be lower on Day 16 compared with Day 12. The episodic secretion of LH shifted from a pattern characterized by high amplitude, low-frequency pulses to one dominated by numerous pulses of diminishing magnitude between Days 13 and 14. From Days 14 to 16 of the oestrous cycle, 91% of all oestradiol pulses were temporally associated with gonadotrophin pulses composed of both FSH and LH episodes. However, pulses of oestradiol (52%) not associated with an episode of LH and/or FSH were observed on Days 12 and 13. These data demonstrate that during the follicular phase of the pig oestrous cycle substantial oestradiol production occurred coincident with luteolysis and before the shift in the episodic secretion of LH. The pool of follicles which ovulated was probably the source of this early increase in the secretion of oestradiol. Therefore, we propose that factors in addition to FSH and LH are involved in the initial selection of follicles destined to ovulate during the early stages of the follicular phase of the pig oestrous cycle. In contrast, high-frequency, low amplitude pulses composed of LH and FSH were the predominant endocrine signal associated with oestradiol secretion during the second half of the oestrous cycle.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1899884 TI - Expression of prolactin gene in incubating hens. AB - Steady-state levels of the 1.38-kb mRNA encoding the prolactin prohormone, measured by northern and dot blotting using a radioactive cDNA probe, rose 10 fold with concomitant increases in concentrations of prolactin in anterior pituitary and plasma from non-incubating to incubating stages in Gifujidori bantam hens. Daily injections of a low dose of thyrotrophin-releasing hormone (TRH, 0.25 micrograms/kg) for 4 days caused no changes in the concentrations of prolactin of the mRNA, but a high dose (2.5 micrograms/kg) of TRH did induce a significant increase in prolactin mRNA levels compared to saline controls. The results suggest that gene expression for prolactin increases substantially during the incubation period and TRH may contribute, at least in part, to the increase in transcription of prolactin mRNA for prolactin biosynthesis in Gifujidori bantam hens. PMID- 1899885 TI - Decreased follicular steroids and insulin-like growth factor-I and increased atresia in diabetic gilts during follicular growth stimulated with PMSG. AB - Four streptozotocin-diabetic gilts (maintained on exogenous insulin for 3 months) and 4 normoglycaemic gilts were treated with 600 i.u. PMSG. Diabetic gilts had insulin therapy removed at the time of PMSG administration. Plasma glucose averaged 463 +/- 5 mg/100 ml for diabetic gilts and 82 +/- 4 mg/100 ml for control gilts over the 72-h sampling period. Serum insulin was lower in diabetic than in normoglycaemic gilts (glycaemic state by time interaction; P less than 0.0001). At ovary removal 75 h after PMSG, numbers and percentages of large (greater than or equal to 7 mm) and medium (3-6 mm) non-atretic follicles were similar for diabetic and control gilts (31 vs 68%; s.e.m. = 7; P less than 0.05). Diabetic gilts had a greater percentage of atretic follicles over all size classes (50 vs 21%; s.e.m. = 7; P less than 0.03). After PMSG, LH was suppressed within 12 h in control gilts and remained similar to values in diabetic gilts until 72 h, when LH was elevated in 2 diabetic gilts (glycaemic state by time interaction; P less than 0.001). Pulsatile LH patterns during 52-55 h after PMSG were not affected by glycaemic state. Serum concentrations of IGF-I tended (P less than 0.1) to be lower in diabetic gilts. Concentrations of oestradiol and FSH in serum were similar in diabetic and control gilts. Follicular fluid concentrations of oestradiol in follicles greater than or equal to 7 mm were lower in diabetic than normoglycaemic gilts (341 vs 873 ng/ml; s.e.m. = 86; P less than 0.05). Testosterone was higher in follicles 3-6 mm in diameter in diabetic than in normoglycaemic gilts (142 vs 80 ng/ml; s.e.m. = 26; P less than 0.05). Progesterone concentrations in follicular fluid were not affected by glycaemic state. Concentrations of IGF-I in follicles greater than or equal to 7 mm were lower in diabetic than control gilts (150 vs 200 ng/ml; s.e.m. = 13; P less than 0.05). We conclude that follicles of diabetic gilts respond to external gonadotrophic stimulation with decreased hormone production and increased ovarian follicular atresia, despite an absence of effects on circulating gonadotrophin and oestradiol concentrations. PMID- 1899887 TI - Plasma LH, FSH and testosterone concentrations in adult rams which were homozygous carriers or non-carriers of the Booroola fecundity gene. AB - No gene-specific differences were found with respect to LH or testosterone pulsatile secretion (over 12 h), or in 12 hourly mean FSH concentrations in adult Booroola FF and ++ rams. Also, no differences between genotypes in the LH response to an injection of testosterone propionate, the FSH response to an infusion of bovine follicular fluid, or the testosterone response to injections of PMSG were noted. However, during the phase of seasonal testicular development, mean testosterone pulse amplitude (over 12 h) and the FSH response to 25 micrograms GnRH were higher in FF than in ++ rams (P less than 0.05); there were also significant effects of sire (P less than 0.05 in FF genotype only) and litter size (P less than 0.05) on testosterone pulse amplitude and GnRH stimulated FSH release, respectively. During the breeding season, mean LH, but not FSH, concentrations were higher in FF than in ++ rams, after an injection of 0.5 micrograms GnRH; LH release was not affected by sire or litter size (P greater than 0.05). Long-term studies revealed that the FF rams were born in significantly larger litters, they weighed significantly less than ++ rams (P less than 0.05), and that bodyweight was significantly correlated (P less than 0.05) with litter size. There were no differences in testis size, and testis size was not significantly correlated with bodyweight. There was a strong tendency (P = 0.056) for overall mean FSH concentrations, measured weekly for 9 months, to be highest more often in FF than in ++ rams.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1899886 TI - Secretory patterns of LH and FSH during development and hypothalamic and hypophysial characteristics following development of steroid-induced ovarian follicular cysts in dairy cattle. AB - Two experiments were conducted to (1) investigate developmental endocrinology of ovarian follicular cysts (cysts) in cattle and (2) evaluate effects of cysts on hypothalamic and hypophysial characteristics. Cysts were induced with oestradiol 17 beta (15 mg) and progesterone (37.5 mg) dissolved in alcohol and injected s.c. twice daily for 7 days. Cysts were defined as the presence of follicular structures (which may or may not have been the same structure) of 2.0 cm in diameter or greater that were present for 10 days without ovulation and corpus luteum development. In Exp. 1,22 non-lactating, non-pregnant Holstein cows were allocated to 3 groups. Beginning on Day 5 (oestrus = Day 0) of the oestrous cycle, 7 cows (Controls) were treated with twice daily s.c. injections of ethanol (2 ml/injection) for 7 days. Luteolysis was then induced with PGF-2 alpha and blood samples were collected daily every 15 min for 6 h from the morning after the PGF-2 alpha injection (Day 13) until oestrus. Steroids to induce cysts were injected as previously described into the remaining cows (N = 15). Three blood samples were collected at 15-min intervals every 12 h throughout the experimental period. Additional blood samples were collected every 15 min for 6 h on a twice weekly basis. After steroid injections, follicular and luteal structures on ovaries were not detected via rectal palpation for a period of 36 +/- 4 days (static phase). Then follicles developed which ovulated within 3-7 days (non cystic; N = 7) or increased in size with follicular structures present for 10 days (cystic; N = 8). Mean (+/- s.e.m.) concentrations of LH, FSH, oestradiol-17 beta and progesterone in serum remained low and were not different during the static phase between cows that subsequently developed cysts or ovulated. During the follicular phase, mean serum concentration of LH (ng/ml) was higher (P less than 0.1) in cows with cysts (2.9 +/- 0.2) than in cows without cysts (1.1 +/- 0.1) or control cows (1.4 +/- 0.2). In addition, LH pulse frequency (pulses/6 h) and amplitude (ng/ml) were higher (P less than 0.1) in cows with cysts (3.6 +/- 0.3 and 2.2 +/- 0.3, respectively) than in non-cystic (2.3 +/- 0.2 and 1.0 +/- 0.2, respectively) and control (1.8 +/- 0.1 and 1.1 +/- 0.2, respectively) groups during the follicular phase. There were no differences in the FSH, oestradiol-17 beta or progesterone characteristics in cows of any of the 3 groups during the follicular phase.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1899888 TI - Opioidergic control of gonadotrophin secretion in the prepubertal gilt during restricted feeding and realimentation. AB - Prepubertal gilts, having undergone a 7-day period of feed restriction to a maintenance ration, were allocated to one of 4 treatments; restricted feeding at 09:00 and 17:00 h for an 8th day both with (Group RN) and without (Group R) administration of the opioid antagonist naloxone hydrochloride (1 mg.kg-1 at 09:30 h followed by 0.5 mg.kg-1 at hourly intervals for 7 h), or feed to appetite with (Group ALN) and without (Group AL) naloxone administration. Gilts were bled at 10-min intervals on Day 8 from morning to evening feed and plasma LH, FSH and prolactin concentrations were measured by radioimmunoassay. Compared with Group R gilts, Group AL gilts exhibited significantly (P less than or equal to 0.05) higher mean and maximum LH concentrations and pulsatility, lower prolactin concentrations (P less than 0.05) but no significant difference in FSH secretion. Naloxone significantly depressed the increase in LH after re-feeding (Group ALN) (P less than 0.05). Once again there were no significant effects on FSH secretion. Naloxone also significantly depressed prolactin secretion in feed restricted gilts (P less than 0.05). These results confirm that re-feeding of feed-restricted prepubertal gilts stimulates an immediate increase in LH secretion and that this elevation is not mediated via a suppression of inhibitory endogenous opioidergic tone. Rather, naloxone treatment appeared to expose a latent inhibition of LH secretion. The control of LH secretion is distinct from that of FSH in this model. PMID- 1899890 TI - Serum FSH-suppressing activity of human recombinant inhibin A in male and female rats. AB - After a single i.v. injection of purified human recombinant inhibin A (hr inhibin) or bovine follicular fluid (bFF) to 3-day castrated 35-day-old male rats, serum FSH concentrations fell (P less than 0.05) between 4 and 8 h, returning to control concentrations by 16-24 h. Administration of graded doses of hr-inhibin (0.625-10 micrograms/100 g body wt) and bFF (31.3-250 microliters/100 g body wt) resulted in a parallel dose-related suppression of serum FSH with a maximum suppression 50% of controls. Similar experiments in 2-day ovariectomized 85-day-old female rats also showed a dose-related suppression with a maximum suppression approximately 30% of controls. Serum LH concentrations remained unchanged in all studies with male or female rats. The biological activity of hr inhibin in vivo was determined for male and female rats in terms of a standard bFF preparation defined by an in-vitro bioassay based on the suppression of FSH content in rat pituitary cells in culture. In males hr-inhibin exhibited a biopotency of 407 (159:1050; fiducial limits) U/micrograms protein and in females the biopotency was 358 (226:565) U/micrograms protein. These potencies are lower than that measured in the in-vitro bioassay (1120 (1040:1210) U/micrograms protein) and differences between in-vivo and in-vitro systems were attributed to the use of bFF rather than a purified human inhibin preparation as standard. These results indicate that hr-inhibin behaves similarly in vivo to bFF. Furthermore, based on the large working range and relatively good precision, the female rat system provides a good basis for an inhibin in-vivo bioassay method. PMID- 1899889 TI - Developmental changes in pituitary-gonadal function in free-ranging lions (Panthera leo leo) of the Serengeti Plains and Ngorongoro Crater. AB - Pituitary-gonadal function was examined in male lions free-ranging in the Serengeti Plains or geographically isolated in the Ngorongoro Crater of Tanzania. Lions were classified by age as adult (6.1-9.8 years), young adult (3.3-4.5 years) or prepubertal (1.4-1.6 years, Serengeti Plains only). Each animal was anaesthetized and then bled at 5-min intervals for 100 min before and 140 min after i.v. administration of saline or GnRH (1 micrograms/kg body weight). Basal serum LH and FSH concentrations were similar (P greater than 0.05) among age classes and between locations. In Serengeti Plains lions, net LH peak concentrations after GnRH were approximately 35% greater (P less than 0.05) in prepubertal than in either adult or young adult animals. GnRH-stimulated LH release was similar (P greater than 0.05) between adult and young adult lions, and these responses were similar (P greater than 0.05) to those measured in Ngorongoro Crater lions. Basal and GnRH-stimulated testosterone secretion was higher (P less than 0.05) in adult than in young adult lions and lowest (P less than 0.05) in prepubertal lions. Age-class differences in testosterone production were related directly to the concentrations of LH receptors in the testis (P less than 0.05). Basal and GnRH-stimulated testosterone secretion and gonadotrophin receptor concentrations within age classes were similar (P greater than 0.05) between lions of the Serengeti Plains and Ngorongoro Crater. Lower motility and higher percentages of structurally abnormal spermatozoa were observed in electroejaculates of young adult compared to adult Serengeti Plains males (P less than 0.05) and were associated with decreased steroidogenic activity. In contrast, there were no age-related differences in ejaculate characteristics of Ngorongoro Crater lions. Seminal quality in the Crater population was poor in adult and young adult animals and was unrelated to alterations in pituitary or testicular function. In summary, only seminal quality in adult male lions was affected by location, whereas age significantly affected both basal and GnRH stimulated testosterone secretion and seminal quality (Serengeti Plains only) in sexually mature males. The striking seminal/endocrine differences among pride (breeding) males of different ages raises questions about the impact of age on individual reproductive performance in this species. PMID- 1899891 TI - N-(4-Isoxazolylthiazol-2-yl)oxamic acid derivatives as potent orally active antianaphylactic agents. AB - A series of N-(4-isoxazolylthiazol-2-yl)oxamic acid derivatives was synthesized and tested on the passive cutaneous anaphylaxis (PCA) model in rats to verify its potential antianaphylactic activity. These compounds were prepared by reaction of an appropriate bromoacetylisoxazole with thiourea to give the corresponding aminothiazole and subsequent condensation with an oxalic acid monoester chloride to yield, following the usual process, the oxamic acid derivatives. Most of the new compounds exhibited, by intraperitoneal route in rats, a very potent antianaphylactic activity on PCA response, higher than that of the reference compound disodium cromoglycate (DSCG). The new derivatives, in contrast with DSCG, were effective on PCA even by oral route. The most interesting derivative of the new series was N-[4-(3-methyl-5-isoxazolyl)-2-thiazolyl]oxamic acid 2 ethoxyethyl ester (49), which was also active and more potent than DSCG in experimental models involving either IgE- or IgG-mediated anaphylactic responses at bronchopulmonary level. PMID- 1899892 TI - The relation between involvement of the central nervous system in schistosomiasis mansoni and the clinical forms of the parasitosis. A review. AB - A review of the available literature on the involvement of the central nervous system (CNS) in schistosomiasis mansoni was undertaken to assess the schistosomal lesions in the spinal cord and brain and the clinical forms of the disease that are associated with these lesions. In almost all clinically symptomatic cases of neuroschistosomiasis mansoni (NSM), involvement of the CNS starts in the early stages of infection (non-toxaemic form), during evolution of the disease to its chronic forms, or concomitantly with the (oligo or asymptomatic) chronic intestinal and hepatointestinal forms. In-situ ova deposition following the anomalous migration of adult worms appears to be the main, if not the only, mechanism by which Schistosoma mansoni may reach the CNS in patients with the intestinal and hepatointestinal forms of the parasitosis. The mass effect produced by the heavy concentration of ova and granulomas in circumscribed areas of the spinal cord and brain explains the severe neurological symptoms observed in most of these patients. Though more frequent, CNS involvement associated with the hepatosplenic and cardiopulmonary forms is almost always asymptomatic. The random distribution of ova in the CNS of patients with these forms suggests that ova are carried there mainly as emboli via the arterial system or through retrograde venous flow. Because of the discrete inflammatory reaction elicited by the sparsely distributed ova, neurological symptoms attributable to ova deposition are not present in most NSM patients with the hepatosplenic and cardiopulmonary forms. PMID- 1899894 TI - The benefit to cost ratio of work-site blood pressure control programs. AB - Reduction in the cost of health care claims among hypertensive employees was examined over a 4-year period after exposure to a 3-year blood pressure control program, to see whether work-site monitoring and counseling produced a subsequent benefit. Hypertensive employees at three experimental sites (N = 183 to 367 subjects) were compared with subjects at a control site (N = 169) who had received no postscreening follow-up or monitoring, and with matched normotensive employees. The cost of subsequent health care claims for hypertensive employees at the experimental sites was lower than claims for those at the control site, but there was no significant difference across the sites in claims for normotensive employees. After adjusting to a standard 1982 dollar, the data showed from $1.89 to $2.72 in reduced health care claims per dollar spent operating the hypertension control program. PMID- 1899893 TI - Production of random classes of immunoglobulins in brain tissue during persistent viral infection paralleled by secretion of interleukin-6 (IL-6) but not IL-4, IL 5, and gamma interferon. AB - The activities of cytokines were determined in cerebrospinal fluid (CSF) and serum of mice persistently or intracerebrally acutely infected with lymphocytic choriomeningitis (LCM) virus (LCMV). In contrast to CBA/J (LCMV carrier) mice that responded with low levels of LCMV-specific antibody, high-responder NMRI (carrier) mice showed antibody production by B cells outside of lymphoid organs. The B cells that had infiltrated the brains of LCMV carrier mice exhibited no preferential immunoglobulin isotype or subtype virus-specific antibody production. Phenotypic analysis of the brain infiltrates in virus carrier mice revealed dominance of CD4+ T cells in contrast to virtual absence of CD4+ and dominance of CD8+ in mice with acute LCM. In NMRI but not in CBA/J carrier mice, significant concentrations of interleukin-6 (IL-6) were detected in CSF and serum; IL-2, IL-4, IL-5, granulocyte-macrophage CSF (GM-CSF), and gamma interferon (IFN-gamma) were not elevated. In contrast, during acute, lethal LCM, IL-6 and IFN-gamma were found at high concentrations, and IL-4, IL-5, and GM-CSF were detectable in CSF and serum, but virus-specific antibody-producing cells were not (yet) detectable in the brain. Thus, distinct cytokine patterns are found in acute versus chronic LCMV infection of the brain: in LCM carrier mice, local random-class immunoglobulin production correlated with the absence of IL-2, IL-4, IL-5, and IFN-gamma but active secretion of IL-6. PMID- 1899895 TI - The prospective payment system: a civic good, not a civil war. PMID- 1899896 TI - Cost-effectiveness of HMG-CoA reductase inhibition for primary and secondary prevention of coronary heart disease. AB - To determine the cost-effectiveness of HMG-CoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase inhibitors (such as lovastatin) for the primary and secondary prevention of coronary heart disease, we used the Coronary Heart Disease Policy Model, a computer-stimulated model that estimates the risk factor specific annual incidence of coronary heart disease and the risk of recurrent coronary events in persons with prevalent coronary heart disease. When used for secondary prevention, 20 mg/d of lovastatin was estimated to save lives and save costs in younger men with cholesterol levels above 250 mg/dL (6.47 mmol/L) and to have a favorable cost-effectiveness ratio regardless of the cholesterol level except in young women with cholesterol levels below 250 mg/dL (6.47 mmol/L). Doses of 40 mg/d of lovastatin had favorable incremental cost-effectiveness ratios in men with cholesterol levels above 250 mg/dL (6.47 mmol/L). By comparison, primary prevention had favorable cost-effectiveness ratios only in selected subgroups based on cholesterol levels and other established risk factors. We conclude that current national recommendations regarding medication for secondary prevention are not as aggressive as our projections would suggest, while recommendations regarding the use of medications for primary prevention should consider the cost of medication as well as the risk factor profile of the individual patient. PMID- 1899897 TI - [Radiation pathomorphosis in single and intensive-concentrated preoperative irradiation of colon cancer]. AB - Single (7.5 Gy) or intensive-concentrated (20 Gy at 5 daily fractions of 4 Gy each) preoperative irradiation was given to 42 colon cancer patients. Operation was performed not later than 24 h after single irradiation and 1-3 days after intensive-concentrated irradiation. Radiation pathomorphosis was studied on histological and electro-microscopic examination of biopsy specimens. Dystrophic changes of tumor cells were noted following the use of both methods, though more noticeable ones were observed after intensive-concentrated irradiation. Obstruction of the microcirculatory bed of a tumor appeared to be a characteristic sign of a tumor stroma response both in single and fractionated irradiation. It was assumed that the latter together with direct radiation damage of tumor cells could be very important to the prevention of implantation recurrences and metastases. PMID- 1899898 TI - A subdermal progestin implant for long-term contraception. PMID- 1899900 TI - Dengue epidemic--Peru, 1990. AB - From March to July 1990, an epidemic of classical dengue caused by dengue types 1 and 4 (DEN-1 and DEN-4) occurred in Iquitos and the surrounding area of the department of Loreto in the Amazon region of Peru (Figure 1). A smaller outbreak was reported in Tarapoto in the neighboring department of San Martin. Although cases were reported in Peru during 1953-1955 and in 1958 (1), the epidemic in 1990 was the first laboratory confirmation of indigenous transmission of dengue in Peru. This report summarizes the preliminary findings of the epidemiologic investigation by the Peruvian Ministry of Health (MOH) and the U.S. Naval Medical Research Institute Detachment (NAMRID), Lima, Peru, which conducted special studies and laboratory confirmation of cases in persons seen at the Peruvian Naval Medical Center, Iquitos, Peru. PMID- 1899899 TI - Pravastatin and simvastatin for hypercholesterolemia. PMID- 1899901 TI - Update: acute allergic reactions associated with reprocessed hemodialyzers- United States, 1989-1990. PMID- 1899903 TI - The gall bladder cholecystokinin receptor exists in two guanine nucleotide binding protein-regulated affinity states. AB - To study proximal events in cholecystokinin (CCK) action on bovine gall bladder smooth muscle, we used the hormone analogue D-Tyr-Gly-[(N1e28,31)CCK-26-32] phenethyl ester (OPE), which has unique biological properties. This fully efficacious agonist differs from native CCK by not expressing supramaximal inhibition of cell shortening, yet it clearly interacts with the same receptor molecule. This was demonstrated in binding and affinity labeling studies, where both peptides label the same Mr 70,000-85,000 protein and both fully compete for binding of the other ligand. Further, its relatively high affinity for the low affinity CCK receptor permits the clear demonstration of two affinity states of a CCK receptor on a membrane preparation and makes possible evaluation of the molecular basis of these affinity states and their regulation. Analysis of homologous and heterologous binding curves performed with both CCK and OPE peptides and radioligands demonstrated the presence of two affinity states, with CCK being able to distinguish them (Kd1 = 0.48 +/- 0.04 nM and Kd2 = 56.5 +/- 7.4 nM) and OPE recognizing them equally (Kd1 = 0.94 +/- 0.31 nM and Kd2 = 0.96 +/- 0.23 nM). In the presence of nonhydrolyzable GTP analogues, there was a shift in distribution of receptors toward the low affinity state, with the total number of receptors and their absolute affinities for each peptide remaining constant. Thus, the gall bladder CCK receptor is a single molecule capable of assuming two interconvertible affinity states, regulated by a guanine nucleotide-binding protein. Two full agonists are capable of interacting with this molecule to yield different biological responses via different molecular events. PMID- 1899902 TI - The A2 adenosine receptor: guanine nucleotide modulation of agonist binding is enhanced by proteolysis. AB - Agonist binding to the A2 adenosine receptor (A2AR) and its regulation by guanine nucleotides was studied using the newly developed radioligand 125I-2-[4-(2-[2-[(4 aminophenyl)methylcarbonylamino] ethylaminnocarbonyl]ethyl)phenyl]ethylamino-5'-N ethylcarboxamidoadenosine (125I-PAPA-APEC) and its photoaffinity analog 125I azido-PAPA-APEC. A single protein of Mr 45,000, displaying the appropriate A2AR pharmacology, is labeled in membranes from bovine striatum, PC12 cells, and frog erythrocytes. In DDT1 MF2 cells the labeled protein has a slightly lower molecular weight. Incorporation of 125I-azido-PAPA-APEC into membranes from rabbit striatum, however, reveals two specifically labeled peptides (Mr approximately 47,000 and 38,000), both of which display A2AR pharmacology. Inhibition of protease activity leads to a decrease in the amount of the Mr 38,000 protein, with only the Mr 47,000 protein remaining. This suggests that the Mr 38,000 peptide is a proteolytic product of the Mr 47,000 A2AR protein. In membranes containing the intact undigested A2AR protein, guanine nucleotides induce a small to insignificant decrease in agonist binding, which is atypical of stimulatory GS-coupled receptors. This minimal effect is observed in rabbit striatal membranes prepared in the presence of protease inhibitors, as well as in the other tissues studied. Binding to rabbit striatal membranes that possess the partially digested receptor protein, however, reveals a 50% reduction in maximal specific agonist binding upon addition of guanine nucleotides. Inhibition of proteolysis in rabbit striatum, on the other hand, results in a diminished ability of guanine nucleotides to regulate agonist binding. Thus, the enhanced effectiveness of guanine nucleotides in rabbit striatal membranes is associated with the generation of the Mr 38,000 peptide fragment. Guanosine 5'-(beta,gamma imido)triphosphate reduces photoaffinity labeling by 55% in the Mr 38,000 protein, whereas the labeling is decreased by only 28% in the Mr 47,000 receptor protein. Our data, therefore, suggest that, unless proteolysis occurs, the A2AR in all tissues studied is tightly associated with the GS protein and displays minimal guanine nucleotide modulation of agonist binding, which makes the A2AR an atypical stimulatory receptor. PMID- 1899904 TI - Stimulation of prostaglandin H synthase mRNA levels and prostaglandin biosynthesis by phorbol ester: mediation by protein kinase C. AB - We have investigated the mechanisms by which the tumor promoter 12-O tetradecanoylphorbol-13-acetate (TPA) stimulates prostaglandin E2 (PGE2) formation in the rat tracheal epithelial cell line EGV-6aigT, which can be grown in serum-free medium. The addition of TPA to cells that were prelabeled with [3H]arachidonic acid did not enhance the release of [3H]arachidonic acid and/or [3H]PGE2, indicating that TPA does not stimulate phospholipase activity. The addition of exogenous arachidonic acid to cells pretreated with TPA resulted in increased PGE2 formation, compared with basal levels, indicating an elevation in prostaglandin H synthase (PHS) activity. PHS activity was maximal at 4 hr and was dependent upon the concentration of TPA. Actinomycin D and cycloheximide blocked the TPA response. The recovery of PHS activity of cells in which the existing PHS was inhibited by aspirin was enhanced by TPA treatment. TPA treatment enhanced the expression of PHS mRNA, as measured by Northern analysis. The addition of actinomycin D and cycloheximide reduced the TPA enhancement of PHS mRNA, indicating that the increase in PHS activity required de novo RNA and protein synthesis. Furthermore, pretreatment of the cells with protein kinase C inhibitors reduced the TPA-dependent stimulation of PHS activity and the expression of PHS mRNA. The data suggest that TPA-stimulated de novo synthesis of PHS is mediated by protein kinase C. PMID- 1899905 TI - Evidence of paired M2 muscarinic receptors. AB - Binding assays involving various antagonists, including N-[3H] methylscopolamine, [3H]quinuclidinyl benzilate, AFDX-116, pirenzepine, and propylbenzilylcholine mustard, disclosed only a single population of M2 muscarinic receptors in membranes from the rat "brainstem" (medulla, pons, and colliculi). However, competition curves between N-[3H]methylscopolamine and various agonists, including oxotremorine, cis-dioxolane, and acetylethylcholine mustard, showed approximately equal numbers of guanine nucleotide-sensitive high affinity (H) sites and guanine nucleotide-insensitive low affinity (L) sites. This 50% H phenomenon persisted in different buffers, at different temperatures, after the number of receptors was halved (and, thus, the remaining receptor to guanine nucleotide-binding protein ratio was doubled), after membrane solubilization with digitonin, and when rabbit cardiac membranes were used instead of rat brainstem membranes. Preferential occupation of H sites with acetylethylcholine mustard, and of L sites with quinuclidinyl benzilate or either mustard, yielded residual free receptor populations showing predominantly L and H sites, respectively. Low concentrations of [3H]-oxotremorine-M labeled only H sites, and the Bmax for these sites was 49% of the Bmax found with [3H]quinuclidinyl benzilate plus guanine nucleotide. These and other results are most consistent with the idea that H and L receptor sites exist on separate but dimeric receptor molecules and with the hypothesis that only the H receptors cycle between high and low affinity, depending upon interactions between this receptor molecule and a guanine nucleotide-binding protein. PMID- 1899906 TI - Multiple basal promoter elements determine the level of human c-fos transcription. AB - Three cis-acting domains that contribute to the basal promoter activity of the human c-fos gene were identified. One encompasses the serum response element and has been previously described. Another spans an NF1-like site situated at -170. Mutations and in vitro protein binding assays pinpoint this site as the sole basal element of the medial domain. The third, or promoter-proximal, domain can be divided into several distinct sites, one containing a directly repeated GC rich element and the other consisting of partially overlapping recognition sites for transcription factors ATF/CREB and MLTF/USF. Each of these sites contributes to basal activity as assayed by transient transfections and by in vitro transcription. Consistent with this, several complexes could be visualized between this region and nuclear proteins in vitro and genomic footprinting demonstrated that both elements are constitutively bound in vivo. On the basis of these results, we conclude that all three domains are necessary for full c-fos promoter function. PMID- 1899907 TI - Silencing of the expression of the immunoglobulin kappa gene in non-B cells. AB - Although the activating factor NF-kappa B can be present in the nucleus of many cell types, transcription and rearrangement of the immunoglobulin kappa chain gene is restricted to cells of the B lineage. Part of this specificity is determined by sequences within the major intron of the kappa gene that specifically silence gene expression in non-B cells (T cells and HeLa cells). These sequences are found in a 232-bp fragment located 5' of the NF-kappa B binding sequence of the enhancer. When this fragment is added back upstream of an active NF-kappa B site, it specifically decreases the expression of a linked gene by more than 10-fold in activated T cells but it has no effect on expression in B cells. The kappa silencer region acts in an orientation- and distance-independent manner and appears to be composed of multiple negative elements. The kappa silencer may act to restrict transcription and rearrangement of the C kappa locus to cells of the B lineage. PMID- 1899908 TI - Role of the C-terminal region of smg p25A in its interaction with membranes and the GDP/GTP exchange protein. AB - smg p25A is a ras p21-like small GTP-binding protein which is implicated in the regulated secretory processes. We have recently found that bovine brain smg p25A is geranylgeranylated at its C-terminal region. In this study, we examined the function(s) of the C-terminal region of smg p25A. Limited proteolysis of bovine brain smg p25A with Achromobacter protease I produced an N-terminal fragment and a C-terminal tail. The Mrs of intact smg p25A, the N-terminal fragment, and the C terminal tail were estimated to be about 24,000, 20,000, and less than 2,000, respectively, by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The N terminal fragment contained the consensus amino acid sequences for GDP/GTP binding and GTPase activities and showed these activities with kinetic properties similar to those of the intact protein but did not bind to plasma membranes or phosphatidylserine-linked Affigel under conditions in which the intact protein bound to them. The C-terminal tail neither contained the consensus amino acid sequences for GDP/GTP-binding and GTPase activities nor bound to plasma membranes or phosphatidylserine-linked Affigel. The GDP/GTP exchange protein specific for smg p25A, named GDP dissociation inhibitor (GDI), made a complex with the GDP bound form of the intact smg p25A at a molar ratio of 1:1 and thereby inhibited its GDP/GTP exchange reaction but neither made a complex with the N-terminal fragment or the C-terminal tail nor affected the GDP/GTP exchange reaction of the N-terminal fragment. We expressed smg p25A in Escherichia coli and purified it to near homogeneity. This bacterial protein was not geranylgeranylated. Bacterial smg p25A did not bind to plasma membranes or phosphatidylserine-linked Affigel. smg p25A GDI neither made a complex with bacterial smg p25A nor affected its GDP/GTP exchange reaction. These results suggest that the N-terminal region of smg p25A has GDP/GTP-binding and GTPase activities but lacks the ability to interact with membranes and smg p25A GDI, that the C-terminal region of smg p25A plays important roles in its interaction with membranes and smg p25A GDI, and that some modifications of the C-terminal region, such as geranylgeranylation, which are absent in bacterial smg p25A, are important for these interactions. PMID- 1899911 TI - Micronucleus formation in cultured human keratinocytes following exposure to mitomycin C and cyclophosphamide. AB - A method is described to investigate the induction of micronuclei in cultured human keratinocytes after short-term exposure to known clastogenic agents. The cytokinesis-block method was applied to facilitate the scoring of micronucleated cells. Mitomycin C, a direct-acting compound, caused a 5-20-fold increase in micronuclei over the controls at the highest concentration tested (1 microgram/ml). Cyclophosphamide, an agent requiring metabolic activation, did not induce the formation of micronuclei in cultured keratinocytes. However, after pretreatment of the keratinocyte cultures with Aroclor 1254 for 72 h, exposure to cyclophosphamide resulted in a 3-fold increase in micronucleus frequency over the controls. No cytogenetic effect of Aroclor 1254 was observed in control experiments. PMID- 1899909 TI - The COOH-terminal domain of the Rap1A (Krev-1) protein is isoprenylated and supports transformation by an H-Ras:Rap1A chimeric protein. AB - Although the Rap1A protein resembles the oncogenic Ras proteins both structurally and biochemically, Rap1A exhibits no oncogenic properties. Rather, overexpression of Rap1A can reverse Ras-induced transformation of NIH 3T3 cells. Because the greatest divergence in amino acid sequence between Ras and Rap1A occurs at the COOH terminus, the role of this domain in the opposing biological activities of these proteins was examined. COOH-terminal processing and membrane association of Rap1A were studied by constructing and expressing a chimeric protein (composed of residues 1 to 110 of an H-Ras activated by a Leu-61 mutation attached to residues 111 to 184 of Rap1A) in NIH 3T3 cells and a full-length human Rap1A protein in a baculovirus-Sf9 insect cell system. Both the chimeric protein and the full-length protein were synthesized as a 23-kDa cytosolic precursor that rapidly bound to membranes and was converted into a 22-kDa form that incorporated label derived from [3H]mevalonate. The mature 22-kDa form also contained a COOH-terminal methyl group. Full-length Rap1A, expressed in insect cells, was modified by a C20 (geranylgeranyl) isoprenoid. In contrast, H-Ras, expressed in either Sf9 insect or NIH 3T3 mouse cells contained a C15 (farnesyl) group. This suggests that the Rap1A COOH terminus is modified by a prenyl transferase that is distinct from the farnesyl transferase that modifies Ras proteins. Nevertheless, in NIH 3T3 cells the chimeric Ras:Rap1A protein retained the transforming activity conferred by the NH2-terminal Ras61L domain. This demonstrates that the modifications and localization signals of the COOH terminus of Rap1A can support the interactions between H-Ras and membranes that are required for transformation. PMID- 1899912 TI - Sources of variability of the Escherichia coli PQ37 genotoxicity assay (SOS chromotest). AB - To determine the variability in test results obtained with the Escherichia coli PQ37 genotoxicity assay (SOS chromotest) when varying the test protocol, we examined the influences of sodium dodecylsulfate (SDS) concentrations, of buffer pH and composition on the enzyme assays, the effects of E. coli PQ37 density and culture conditions on the expression and/or determination of alkaline phosphatase (ap) and beta-galactosidase (beta-g) activities, the calculated induction factors (IF) and the SOS-inducing potentials (SOSIP). Initially, we used 0-190 ng (0-1 nmole) 4-nitroquinoline-1-oxide (4-NQO) as a reference compound for the standard procedure in the absence of metabolic activation. Subsequently, to evaluate the results of protocol variations we examined several mutagenic compounds of differing chemical classes using both the standard and a modified assay procedure. We observed the highest enzyme activities using 1 mg SDS per tube and calibrating the ap buffer to pH 8.05 and the beta-g buffer to pH 7.75. The longer the incubation period, the higher the enzyme activities. However, with respect to IF and SOSIP there is no reason to incubate in excess of 90 min. We found no significant differences in the IF and SOSIP values when varying substrate conversion times. There was, however, a definite decrease in beta-g activity when extended substrate incubation times were used. Higher enzyme activities are obtained when the bacterial count is increased. Using lower bacterial counts the enzyme activities decreased, but the sensitivity of E. coli towards genotoxic compounds increased. PMID- 1899910 TI - Common factor 1 is a transcriptional activator which binds in the c-myc promoter, the skeletal alpha-actin promoter, and the immunoglobulin heavy-chain enhancer. AB - Ubiquitously expressed transcription factors play an integral role in establishing and regulating patterns of gene transcription. Common factor 1 (CF1) is a ubiquitously expressed DNA-binding protein previously identified in our laboratory. We show here that CF1 recognizes sites in several diverse transcription elements, and we demonstrate the ability of the c-myc CF1 site to activate transcription of a basal promoter in both B cells and fibroblasts. PMID- 1899913 TI - Test of a semiselective screen for induced aneuploidy in germ cells of Drosophila melanogaster females with structurally normal chromosomes. AB - A new semiselective screen (only female progeny survive) for induced aneuploidy in germ cells of Drosophila melanogaster (referred to as 20/Q56 for the X chromosome mutation markers in the parental females) has been validated by recovering cold, colchicine and N,N-dimethylnitrosamine (DMN) induced chromosome gain and loss events in females that contain structurally normal chromosomes. In addition, the spontaneous and induced results from the 20/Q56 assay, which identifies gain events at division I and loss events at divisions I and II of meiosis, were compared with a nonselective (all progeny survive) modified mating scheme that identifies gains and losses at both divisions of oogenesis. Females with the same genotypes are treated in the two mating schemes and are then mated with males that contain different marked Y chromosomes. The spontaneous rates of chromosome gains and losses were not significantly different in the two mating schemes (these rates ranged from 0.008 to 0.022%), supporting previous reports that spontaneous aneuploidy occurs at a higher frequency at division I of meiosis in females of D. melanogaster than at division II. Both the 20/Q56 and modified screens were able to identify significant increases in aneuploidy after adult treatments with cold shock (10 degrees C and 5 degrees C), colchicine (5 ppm and 10 ppm), and DMN (100 ppm). Brood analysis (five 2-day or five 3-day broods) showed that the largest increases in aneuploidy after cold treatment occurred in the first brood, which contains a high proportion of stage 14 oocytes, whereas colchicine induced the highest frequencies in the latter broods and DMN was effective in all but the last brood. Although the 20/Q56 mating scheme identifies gain events only in division I of meiosis whereas the modified mating scheme identifies gains in both divisions, the 20/Q56 scheme is just as effective in identifying induced aneuploidy as is the modified scheme. There were no significant differences in the frequencies of induced gains or losses in the two schemes. These results also suggest that the 3 treatments induced chromosome gain events mainly at division I of oogenesis. Taken together, the results from this study suggest that the 20/Q56 mating scheme in D. melanogaster, which is semiselective and therefore less expensive and time-consuming to perform, is an appropriate test system to screen for chemical induced aneuploidy in germ cells of a higher organism. PMID- 1899914 TI - Neurobiology. A system for synapse control. PMID- 1899915 TI - Familial Alzheimer's disease. Beta amyloid resurrected. PMID- 1899916 TI - Induction of formation of presynaptic terminals in neuroblastoma cells by synapsin IIb. AB - The synapsins are a family of closely related phosphoproteins (termed synapsins Ia, Ib, IIa and IIb) associated with synaptic vesicles and implicated in the short-term regulation of neurotransmitter release from nerve endings. During development, expression of the synapsins correlates temporally with synapse formation, but there has been no direct evidence that they are involved in synaptogenesis. Here we report that overexpression of synapsin IIb in the neuroblastoma x glioma hybrid clonal cell line NG108-15 leads, during cell differentiation, to marked increases in the number of neuritic varicosities and in the numbers of small clear vesicles and large dense core vesicles per varicosity, as well as to the appearance of synapse-like cell-cell contacts. Thus, synapsin IIb may be involved in the regulation of synapse formation and, as a result, in long-term neuronal signalling. PMID- 1899918 TI - The optimum use of laboratory tests in the surgical patient. PMID- 1899917 TI - Alteration of ionic selectivity of a K+ channel by mutation of the H5 region. AB - The high ionic selectivity of K+ channels is a unifying feature of this diverse class of membrane proteins. Though K+ channels differ widely in regulation and kinetics, physiological studies have suggested a common structure: a single file pore containing multiple ion-binding sites and having broader vestibules at both ends. We have used site-directed mutagenesis and single-channel recordings to identify a molecular region that influences ionic selectivity in a cloned A-type K+ channel from Drosophila. Single amino-acid substitutions in H5, the fifth hydrophobic region, enhanced the passage of NH4+ and Rb+, ions with diameters larger than K+, without compromising the ability of the channel to exclude the smaller cation, Na+. The mutations that substantially altered selectivity had little effect on the gating properties of the channel. We conclude that the H5 region is likely to line the pore of the K+ channel. PMID- 1899919 TI - Effects of early discharge planning on length of hospital stay. AB - This experimental research tests the effect of discharge planning on length of hospital stay. In this study of 432 medical patients in a southwestern medical center, discharge planning implemented within 24 hours of hospital admission significantly reduced length of stay. Projected savings to the institution far exceed the cost of implementation. PMID- 1899920 TI - An interview with Joyce C. Clifford. Interview by Carmella A. Bocchino. AB - Various professional practice models have been used to advance nursing. The primary nursing model at Boston's Beth Israel Hospital has continued to be successful for over 15 years and has gained the respect of both the nursing community and the hospital industry. Joyce C. Clifford, MSN, RN, FAAN, Vice President for Nursing and Nurse-in-Chief at Beth Israel, discusses the development and implementation of this practice model and her strategies- continuity and accountability--to advance nursing. PMID- 1899921 TI - [Pheochromocytoma in neurofibromatosis]. PMID- 1899923 TI - Inhibition of the N-end rule pathway in living cells. AB - The N-end rule relates the metabolic stability of a protein to the identify of its amino-terminal residue. Previous work, using amino acid derivatives such as dipeptides to inhibit N-end rule-mediated protein degradation in an extract from mammalian reticulocytes, has demonstrated the existence of specific N-end recognizing proteins in this in vitro system. We now show that these nontoxic amino acid derivatives, when added to growing cells of the yeast Saccharomyces cerevisiae, are able to inhibit the degradation of proteins by the N-end rule pathway in vivo. Moreover, this inhibition is shown to be selective for the two distinct classes of destabilizing amino-terminal residues in substrates of the N end rule pathway. PMID- 1899922 TI - [Ultrasonic examination of ankle and knee ligament injuries]. AB - Ultrasound examinations and stress radiographs of 61 patients with suspected ligamentar lesion of the ankle and knee joints were compared in order to clear, whether radiography could be replaced by sonography. In our experience, the opening of the joint gap can also be adequately demonstrated even without ionizing radiation and the results achieved by ultrasound were nearly as accurate as by X-rays. Being a rather simple, inexpensive and real time method, producing acceptable visual information and practicable on almost all preexisting equipments, sonography is advised for detecting of ligamentar lesions. PMID- 1899924 TI - Mouse hepatocytes migrate to liver parenchyma and function indefinitely after intrasplenic transplantation. AB - One approach to gene therapy for hepatic diseases is to remove hepatocytes from an affected individual, genetically alter them in vitro, and reimplant them into a receptive locus. Although returning hepatocytes to the liver itself would be advantageous, the feasibility of this approach has never been evaluated due to the inability to distinguish donor from host hepatocytes. To unambiguously identify transplanted hepatocytes after transplantation, and to better quantitate their number and degree of liver function, two transgenic mouse lines were generated in a C57BL/6 background. The first expresses the Escherichia coli beta galactosidase gene from the relatively liver-specific human alpha 1-antitrypsin (hAAT) promoter and allows transgenic hepatocytes to be readily identified after 5-bromo-4-chloro-3-indolyl beta-D-galactoside staining; the second produces the hAAT protein under control of the same promoter, which enables hepatocyte survival and maintenance of liver function to be quantitated by measuring the serum levels of hAAT. Hepatocytes isolated from transgenic donors were transplanted into nontransgenic C57BL/6 recipients by intrasplenic injection. Surprisingly, a large fraction of these cells were identified within the liver parenchyma but not the spleen at 2 months after transplantation. The high levels of serum hAAT detected in transplant recipients were stable for greater than 6 months, suggesting that established cells will survive indefinitely. These results have important implications for liver organogenesis and hepatic gene therapy. PMID- 1899925 TI - Interleukin 1 beta induces rapid phosphorylation and redistribution of talin: a possible mechanism for modulation of fibroblast focal adhesion. AB - The majority of interleukin 1 (IL-1) receptors in human fibroblasts has been shown to be localized at focal adhesions. This study describes rapid alterations caused by IL-1 beta/IL-1-receptor interaction at these sites. Fibroblast monolayers, incubated with IL-1 beta and prepared for electron microscopy, showed successive loss of cell-substratum contact and fewer and less-pronounced processes. Immunocytochemistry revealed loss and redistribution of the talin staining initially observed after 5-15 min of IL-1 beta incubation. Similarly, the cytoskeleton showed a decrease in staining and a disorganization starting from 15 to 30 min after IL-1 addition, whereas extracellular fibronectin appeared largely unaffected. Prelabeling with [32P]phosphate showed a 2- to 3-fold increase in the level of talin phosphorylation, peaking at 15 min. Phospho amino acid analyses revealed a higher level of serine and threonine phosphorylation. The data suggest that the action of IL-1 beta on fibroblasts may be partially mediated by direct phosphorylation of talin via activation of a protein serine/threonine kinase, leading to changes in transmembrane linkage proteins and the cytoskeleton. Such alterations at focal adhesions may provide a mechanism by which IL-1 can rapidly modulate cell-matrix interactions during inflammation and wound healing. PMID- 1899926 TI - Gene synthesis, expression, and mutagenesis of the blue copper proteins azurin and plastocyanin. AB - Genes for the blue copper proteins Populus nigra var. italica plastocyanin and Pseudomonas aeruginosa azurin have been constructed by a stepwise procedure. The leader sequence for azurin has been placed before the genes directing plastocyanin and azurin transport to the periplasmic space when the genes are expressed in Escherichia coli. Site-saturation mutagenesis has been used to alter two copper-binding residues of azurin (Met-121 and His-46) and Met-92 of plastocyanin. While the plastocyanin mutants do not appear to bind copper, the azurin variants all bind copper and show characteristic type I blue copper centers. In particular, the electronic spectra reflect the dominance of the charge transfer interaction between copper and the thiolate of Cys-112, being relatively insensitive to changes in Met-121 or His-46. In contrast, removal of Met-121 appreciably alters the EPR spectra of the mutants, although, to a first order, the spectra of all mutants are themselves similar, suggesting a more distorted geometry around copper in the mutants than in the wild type. PMID- 1899927 TI - Amyloid precursor protein in aged nonhuman primates. AB - In individuals with Alzheimer disease and in aged nonhuman primates, deposits of amyloid occur in senile plaques in brain parenchyma and in the walls of some meningeal and cortical vessels. Amyloid is primarily composed of beta/A4, a 4-kDa peptide derived from the transmembrane form of an amyloid precursor protein (APP). We examined the distribution of beta/A4 and APP (outside the beta/A4 domain) in cerebral cortices of monkeys ranging in age from 4 to 41 years. In all animals, APP immunoreactivity was present in cell bodies, proximal dendrites, and axons of cortical neurons. In aged animals, all of which showed senile plaques, large APP-positive axons were conspicuous, and APP immunoreactivity was present in neurites around beta/A4-immunoreactive plaques. In some plaques, APP immunoreactive elements were located in proximity to deposits of beta/A4. The presence of APP immunoreactivity in neuronal perikarya, dendrites, axons, and in neurites within beta/A4-containing plaques supports the hypothesis that neurons can serve as one source of amyloid deposited in brain parenchyma. PMID- 1899928 TI - Gene for non-insulin-dependent diabetes mellitus (maturity-onset diabetes of the young subtype) is linked to DNA polymorphism on human chromosome 20q. AB - Maturity-onset diabetes of the young (MODY) is a form of non-insulin-dependent diabetes mellitus characterized by an early age of onset, usually before 25 years of age, and an autosomal dominant mode of inheritance. The largest and best studied MODY pedigree is the RW family. The majority of the diabetic subjects in this pedigree has a reduced and delayed insulin-secretory response to glucose, and it has been proposed that this abnormal response is the manifestation of the basic genetic defect that leads to diabetes. Using DNA from members of the RW family, we tested more than 75 DNA markers for linkage with MODY. A DNA polymorphism in the adenosine deaminase gene (ADA) on the long arm of chromosome 20 was found to cosegregate with MODY. The maximum logarithm of odds (lod score) for linkage between MODY and ADA was 5.25 at a recombination fraction of 0.00. These results indicate that the odds are greater than 178,000:1 that the gene responsible for MODY in this family is tightly linked to the ADA gene on chromosome 20q. PMID- 1899929 TI - Inducer-dependent conditional-lethal mutant animal viruses. AB - Regulatory elements of the Escherichia coli lac operon were used to construct an inducer-dependent conditional-lethal mutant animal virus. The gene encoding the repressor protein of the lac operon was integrated into the vaccinia virus genome so that it was expressed constitutively, and the lac operator was inserted next to the promoter of a gene that encodes an 11-kDa virion-associated protein of unknown function. The addition of inducer to the cell culture medium provided permissive conditions for isolation of a conditional-lethal mutant virus. Under nonpermissive conditions, the isolated virus did not form plaques, and the yield was decreased by at least 1000-fold under one-step growth conditions. Transcription of the operator-controlled gene was inducer-dependent and necessary for synthesis of the 11-kDa protein. Application of this mutagenesis strategy to other viruses is discussed. PMID- 1899931 TI - HRSA's long range plan for meeting the health care needs of the underserved. PMID- 1899930 TI - Selective targeting of gene products with the megakaryocyte platelet factor 4 promoter. AB - We have used the 1.1 kilobases of the 5' upstream region of the platelet factor four (PF4) gene coupled to the prokaryotic beta-galactosidase gene to generate two lines of transgenic mice that express this construct. Studies of blood, bone marrow, spleen, and thymus reveal that platelets are the only circulating blood cells and megakaryocytes are the only hematopoietic precursor cells that possess the prokaryotic enzyme. The lack of transgene expression in brain, heart, intestine, kidney, liver, lung, and skeletal muscle was established by in situ staining of tissue sections as well as kinetic assay of tissue homogenates. These data suggest that this domain of the PF4 promoter contains most, if not all, of the tissue-specific region of the gene. Unexpectedly, the adrenal gland exhibits approximately 2% of the levels of beta-galactosidase possessed by megakaryocytes and the distribution of the prokaryotic enzyme corresponds to the location of mineralocorticoid-secreting cells. This result implies that either the PF4 gene is transcribed at low levels in specialized adrenal cells or that these specialized endocrine cells possess trans-acting factors similar to those that control the megakaryocyte promoter. The selective high-level expression of transgenes linked to the PF4 promoter should allow us to augment or suppress the in vivo levels of critical components in megakaryocytes and platelets and subsequently ascertain the effects of these modifications. PMID- 1899933 TI - NIAID, AmFAR launch huge new study of HIV infection. PMID- 1899932 TI - HRSA's collaborative efforts with national organizations to expand primary care for the medically underserved. AB - As the Federal agency that provides leadership in expanding access to primary health care, the Health Resources and Services Administration (HRSA) manages some 50 programs directed toward the delivery of services and strengthening the base of national health resources. An enabling element of the agency's strategy is the expansion of partnerships with national associations, private foundations, and other entities that share a concern for the health care of the medically underserved. Cooperative efforts with national organizations are intended to promote the integration of public and private resources and encourage adoption of efficient approaches to organizing and financing health care. Medical education in the primary care specialties, State programs for women and children, involvement of managed care organizations with low-income populations, and programs concerning the uninsured are the foci of some of these collaborative relationships. PMID- 1899934 TI - The diversity of case management needs for the care of homeless persons. AB - Health care providers have been attempting to meet the special needs of homeless people on a national level since 1984. The need to implement strategies specific to serving the diversity of services required by homeless people has been apparent. To devise appropriate strategies, clinical information was drawn from the Health Resources and Services Administration-Health Care for the Homeless (HRSA-HCH) projects, which were created in 1987 primarily to fill such a need. In addition, data gathered by the HCH projects (1984-87) funded by the Robert Wood Johnson and Pew Memorial Trust were used. It is suggested that the past mode of providing health care for the homeless has been found to be inadequate when confronting the complex problems of the homeless person of today. In general, health care providers need to focus more on case management activities, which may include activities not necessarily associated with the provision of health care services (for example, finding and providing food, clothing, shelter, and assessing entitlement eligibility) to achieve the ultimate goal--stabilization- and when possible, reintegration of the homeless person back into society. PMID- 1899935 TI - Report on a seminar on financing and service delivery issues in caring for the medically underserved. AB - Current national activities directed toward improving access to health care and assessing the potential effectiveness of various financing and service delivery strategies were reviewed by an invited group of 39 public and private sector health policy experts. Health care access problems of the medically underserved population were defined and a range of strategies for addressing them were presented. The seminar was held at Columbia, MD, July 6-7, 1988, sponsored jointly by the Robert Wood Johnson Foundation and the Health Resources and Services Administration, PHS. PMID- 1899936 TI - The role of public health in providing primary care for the medically underserved. AB - Strategies designed to meet the health care needs of Americans should include the issues of access as well as financing. And primary care and clinical preventive services should receive as much national attention as acute care and long-term care. The public health system at the Federal, State, and local levels with its mandate to assure conditions in which people can be healthy must also be incorporated into the national debate. Publicly funded infrastructures for delivering primary health care have become a significant element of assuring access at the community level. This paper examines the expanding role of public health in assuring access to the delivery of primary health care and clinical preventive services to vulnerable populations within the larger issue of who should have access to care and how it should be made available. Special attention is paid to the part played by the Health Resources and Services Administration (HRSA) of the Public Health Service, which, in the Federal fiscal year that began on October 1, 1989, administered some $1.8 billion worth of programs for health care of targeted populations and for the support of training in the health professions. PMID- 1899937 TI - Consequences of the nuclear power plant accident at Chernobyl. AB - The Chernobyl Nuclear Power Plant accident, in the Ukrainian Soviet Socialist Republic (SSR), on April 26, 1986, was the first major nuclear power plant accident that resulted in a large-scale fire and subsequent explosions, immediate and delayed deaths of plant operators and emergency service workers, and the radioactive contamination of a significant land area. The release of radioactive material, over a 10-day period, resulted in millions of Soviets, and other Europeans, being exposed to measurable levels of radioactive fallout. Because of the effects of wind and rain, the radioactive nuclide fallout distribution patterns are not well defined, though they appear to be focused in three contiguous Soviet Republics: the Ukrainian SSR, the Byelorussian SSR, and the Russian Soviet Federated Socialist Republic. Further, because of the many radioactive nuclides (krypton, xenon, cesium, iodine, strontium, plutonium) released by the prolonged fires at Chernobyl, the long-term medical, psychological, social, and economic effects will require careful and prolonged study. Specifically, studies on the medical (leukemia, cancers, thyroid disease) and psychological (reactive depressions, post-traumatic stress disorders, family disorganization) consequences of continued low dose radiation exposure in the affected villages and towns need to be conducted so that a coherent, comprehensive, community-oriented plan may evolve that will not cause those already affected any additional harm and confusion. PMID- 1899939 TI - Addressing barriers to perinatal care: a case study of the Access to Maternity Care Committee in Washington State. AB - Access to obstetrical services has deteriorated in recent years, as large numbers of physicians have discontinued or restricted obstetrical practice. In Washington State, one response to this access crisis has been the establishment of the Access to Maternity Care Committee (AMCC), an ad hoc group composed primarily of private sector obstetrical providers and representatives of State government responsible for the delivery of health care to women and children. The major objectives of the AMCC is to improve access to obstetrical services for socially vulnerable women, both rural inhabitants and the medically indigent. The committee has been successful in serving as a forum in which to resolve many of the administrative problems that have arisen between private sector obstetrical providers and the State's Medicaid Program, the major source of payment for the one-third of pregnant women who are medically indigent. Building upon the trust that the committee members developed in working together, the AMCC served as a major force in persuading the State legislature to expand substantially its investment in perinatal care by increasing Medicaid eligibility, raising provider reimbursement, and improving social service for pregnant women. Such ad hoc coalitions between the private and public sector may be quite effective in addressing obstetrical access problems in other States. PMID- 1899938 TI - Mortality, cardiovascular risk factors, and diet in China, Finland, and the United States. AB - Mortality, cardiovascular risk factors, and diet were compared in Tianjin province, People's Republic of China; in North Karelia Province, Finland; and in the United States as a whole. People in Tianjin received 7 percent of their energy intake from saturated fats, whereas people in the United States received 13 percent and those in North Karelia received 20. The mean blood cholesterol levels for men were 158 milligrams per deciliter (mg per dl) for Tianjin, 216 mg per dl for the United States, and 241 mg per dl for North Karelia. The smoking prevalence among men was highest in Tianjin (66 percent), followed by the United States (42 percent) and Finland (36 percent). The differences among mortality rates for the three locales were less pronounced among women than among men. Age standardized total mortality for women was highest for Tianjin and lowest in North Karelia. The reverse was true for men. Age-standardized total mortality for men was lowest in Tianjin and highest in North Karelia. Age-standardized ischemic heart disease mortality for men was lowest in Tianjin (99 per 100,000) and highest in North Karelia (730 per 100,000). For women, the corresponding figures were 83 per 100,000 in Tianjin and 164 per 100,000 in North Karelia. Although salt intake was higher in Tianjin than in North Karelia, the blood pressure was on average lower in persons from Tianjin than in those from North Karelia. The stroke mortality rate in Tianjin, however, was much higher than in either Finland or the United States. The strong discrepancy in stroke mortality relative to prevalence of hypertension and salt intake raises the issue of the etiology of stroke in Tianjin. Recently it has been reported that hemorrhagic stroke may be more common among people whose blood cholesterol level is very low and blood pressure level high. This joint condition may be relatively common in Tianjin and calls for longitudinal and case-control studies to clarify the relationships among these factors in Tianjin. PMID- 1899940 TI - Changes in characteristics of women who smoke during pregnancy: Missouri, 1978 88. AB - The Missouri birth certificate has had a question, "cigarettes smoked per day?" since 1978; the current data base contains more than 800,000 records. A comparison of the Missouri data for married mothers with the National Natality Survey (NNS) data shows mainly consistent findings between the two data sets. The Missouri data, however, also provided information on the smoking status during pregnancy of unmarried women that is not available from the NNS. The Missouri data show a substantial difference in the smoking rates of married (23.2 percent) and unmarried (40.9 percent) women. The highest smoking rates during pregnancy are found among unmarried women, ages 20-24, with less than a high-school education, and those with a fourth or higher order child. There has been a relatively small overall drop in the smoking rate from 1978-80 to 1986-88 (31.1 percent versus 27.5 percent). However, blacks and teenagers have had very substantial drops in smoking rates. There has been only a slight decrease for other high-risk groups such as white unmarried women, women with less than a high school education, and those having a fourth or higher order birth. Missouri started using the new national standard birth certificate in 1989 with a differently worded smoking question. The percentage of women smoking and those smoking less than one pack per day in 1989 went down more than would be expected from the trend data. It appears that the new birth certificate question will provide a lower estimate of the percentage of mothers who smoke cigarettes than was acquired from the previous version on the Missouri certificate. The births in Missouri for which mothers' rate of smoking was unknown increased nearly fourfold to 0.9 percent. PMID- 1899941 TI - HRSA's role in primary care and public health in the 1990s. AB - The principal responsibility of the Health Resources and Services Administration (HRSA) is to see to it that primary health care services and qualified health personnel and facilities are available to all Americans, particularly the disadvantaged and the underserved. HRSA's resources are directed toward not only the most financially, functionally, and culturally vulnerable segments of the population but also to those who have significant clinical needs such as pregnant women, children, those infected with HIV. The Agency seeks to carry out its mission in many ways. The central approach, however, is to assure the availability of services to its constituencies directly or indirectly through the more than 50 programs it administers. This article explains HRSA's role in detail and cites its many ramifications for the nation's health in the 1990s. PMID- 1899942 TI - Cancer mortality in Cuba and among the Cuban-born in the United States: 1979-81. AB - The Cuban-born population of the United States, enumerated at 608,000 in the 1980 census, has been little studied with regard to cancer mortality. Being older and rarely migrating back to Cuba, Cuban Americans present a good subject for comparative cancer mortality. Age-adjusted death rates for selected causes of cancer are compared in this paper for Cubans in Cuba, the Cuban-born in the United States, and all whites in the United States. Two forms of cancer have been of particular concern in Cuba, cancer of the lung and cancer of the prostate, because of their relatively high death rates. The age-adjusted death rates for both of these cancers are lower among the Cuban-born in the United States than they are among Cubans in Cuba and whites in the United States. Death rates for cancer of the cervix and cancer of the rectum among the Cuban-born in this country are also low relative to Cubans in Cuba and whites in the United States. Stomach cancer mortality among Cuban-born men in the United States is lower than for men in Cuba or for white men in the United States, but Cuban-born women in this country have rates that are slightly higher than those of U.S white women. Mortality rates from colon cancer in both sexes and breast cancer among women are intermediate between the lower rates in Cuba and the higher rates among U.S. whites. Finally, the Cuban-born in the United States have higher death rates from cancer of the liver than do Cubans in Cuba or whites in the United States. In general, the profile found for the Cuban-born in the United States reflects the high socioeconomic status of the pre-1980 migrants as well as their exposure to the U.S. environment. PMID- 1899943 TI - Use of process evaluation to guide health education in Forsyth County's project to prevent cervical cancer. AB - The Forsyth County, NC, Cervical Cancer Prevention Project is a 5-year public health education program designed to increase the proportion of black women in the county who are appropriately screened for cervical cancer. In this paper, the authors report on process evaluation--the procedures used to monitor the intervention and to insure that the target population was reached with a high quality, community-based health education program. A system that encompasses documentation of program activities, interviews with women in waiting rooms of primary care providers, semiannual interviews with a panel of approximately 100 women from the target population, and telephone followup with participants in direct education workshops was designed and implemented. Through October 1990, more than 2,100 interviews had been conducted. Data from these activities have facilitated continued development and refinement of educational materials, provided guidance for developing new strategies for reaching the target population, and provided continuous feedback to program managers to allow monitoring the impact of all program activities. PMID- 1899944 TI - Demographic characteristics, drug use, and sexual behavior of i.v. drug user with AIDS in Bronx, New York. AB - Intravenous (i.v.) drug users are a key factor in the transmission of human immunodeficiency virus (HIV) infection, yet epidemiologic information about this population, especially those with acquired immunodeficiency syndrome, is scarce. The demographic characteristics, drug use behavior, and sexual practices of i.v. drug users who developed AIDS were prospectively studied at the Montefiore Medical Center from October 1984 to February 1988. The early wave of i.v. drug users with AIDS was characterized by poverty, minority overrepresentation (more than 80 percent were black or Hispanic), and initiation of i.v. drug use at an early age (median age 19 years). Injection of drugs and sharing of needles was frequent. Most had used so-called shooting galleries, but only for a minority of injection episodes. Heroin or cocaine use was almost universal, nearly always accompanied by abuse of another substance, usually alcohol or marijuana. Fewer than a third had ever participated in a methadone maintenance program, but more than 40 percent had been in prison since 1978. All patients had been sexually active, often with partners who were not i.v. drug users. The research suggests a complex interaction existing between high-risk demographic characteristics, drug use practice, and certain types of sexual behavior, all of which contributed to the early spread of HIV infection in this population. Efforts that are directed toward interrupting i.v. drug user-related transmission of HIV need to include consideration of these characteristics. PMID- 1899945 TI - Home blood pressure monitoring for mild hypertensives. AB - A clinical trial of 204 untreated patients with mild hypertension was conducted to assess the effect of home blood pressure monitoring on blood pressure level, pharmacologic treatment, reduction of risk factors, and use of health services. After 1 year, no statistically significant differences were found between the treatment and control groups. The findings indicate that, while home blood pressure monitoring may be useful, it has no measurable short-term impact on these aspects of blood pressure management for patients with mild hypertension. PMID- 1899946 TI - The surveillance of communicable disease in Vermont: who reports? AB - The Vermont Department of Health reviewed 2,035 reports of selected notifiable diseases received from January 1, 1986, through December 31, 1987. Laboratories provided 1,160, or 71 percent, of the initial reports on 1,636 confirmed cases. This demonstrates that laboratories, when required by law and when part of active surveillance, can make a significant contribution to surveillance of infectious disease. A survey of primary care physicians indicated that 18 percent always reported notifiable diseases. The most frequently mentioned reason for lack of reporting was an assumption that the laboratory would report the cases. PMID- 1899947 TI - Differences between Oklahoma Indian infant mortality and other races. AB - Indian infant mortality rates (IMR) in the State of Oklahoma follow a downward linear trend from 13 per 1,000 live births in the 1975-76 period to 5.8 in 1987 88. Data from 7,631 death certificates matched to birth certificates, however, reveal much higher Indian IMR across the time interval than is currently documented. Matching (linking) of infant deaths to birth certificates from 1975 to 1988 indicates that infants born Indian had a 28 percent chance of being misclassified as another race (usually white) on the death certificate. Infants born white or black had less than a 1 percent chance of being misclassified. Misclassification of Indian deaths strongly alters the overall IMR for the Oklahoma Indian population from the currently reported 5.8 per 1,000 (1987-88) to an estimated actual rate of 10.4 per 1,000 for the same period. PMID- 1899948 TI - Image interpretation session. Multiple fibroxanthomas associated with neurofibromatosis. PMID- 1899949 TI - Use of size fractionation of in vitro-activated human B lymphocytes for studies of cell cycle-dependent growth regulation. AB - Cell cycle progression of in vitro-stimulated human B lymphocytes occurs asynchronously. In order to allow detailed studies of growth control in G1, B cells were stimulated with anti-mu and low molecular weight B-cell growth factor (LMW BCGF) for 50 h and subsequently separated into nine fractions of cells by means of centrifugal elutriation. As judged by volume profiles, activation antigen expression and DNA content, the cells in fractions 1-4 were in early to mid-G1, while fractions 5-7 mainly contained cells in late G1, and fractions 8-9 contained cells mainly in S and G2. Cells in fractions 5-7 had passed the commitment point, as demonstrated by a high spontaneous incorporation of [3H]thymidine when recultured in medium alone. Moreover, S-phase entry of these cells was largely unaffected by exogenous growth-promoting or growth-inhibitory signals. Cells in early (fractions 1-2) and intermediate fractions (fractions 3 4) showed a negligible spontaneous [3H]thymidine incorporation, but a significant proportion of these cells progressed to S phase upon restimulation. Moreover, while IL-4 or the anti-CD40 MoAb G28-5 potently stimulated cells in early and intermediate fractions, the responsiveness of LMW BCGF alone was obtained just prior to the commitment point. PMID- 1899950 TI - Ossification of the cervical ligamentum flavum. AB - A case of a 61-year-old man with ossification of the cervical ligamentum flavum is reported. The ossification was located on the left side of C3-4. The symptoms improved with laminectomy and resection. Ossification of the ligamentum flavum usually occurs in the lower thoracic spine, and is rare in the cervical region. Including the present one, only eight cases have been reported to our knowledge. The clinical features and pathogenesis are discussed. PMID- 1899951 TI - Reliable confirmation and quantitation of human immunodeficiency virus type 1 antibody using a recombinant-antigen immunoblot assay. AB - The recombinant DNA-derived, human immunodeficiency virus (HIV) antigen-based immunoblot assay (RIBA-HIV216) is a new supplemental (confirmatory) test developed to detect antibodies to HIV-1. The assay employs four recombinant viral antigens, corresponding to HIV-1 p24, p31, p41 and gp120 proteins, in an immunoblot format. With this assay, HIV-1 antigen reactivity was detected in all 683 infected patient serum or plasma specimens evaluated; 665 (97.6%) of these sera met the criteria for a positive interpretation, and 18 (2.6%) were classified as indeterminate. All 683 samples reacted with the recombinant gp41 equivalent protein. The first sequential enzyme immunoassay (EIA)-reactive samples collected from 33 seroconverting homosexual men reacted on RIBA-HIV216. Eleven (1.1%) of 999 EIA-negative blood donor sera reacted weakly with a single recombinant antigen (p24 or p31), whereas 13 to 48 percent had indeterminate reactions on viral lysate Western blots. One (1.5%) of 66 EIA-positive, Western blot-negative blood donor samples and 19 (29%) of 66 EIA-positive, Western blot indeterminate blood donor samples scored indeterminate on RIBA-HIV216. Nonspecific reactivity was seen with only 1 (0.8%) of 114 patient sera containing possible interfering antibodies, whereas 33 percent of these samples had indeterminate reactions on Western blot and 35 percent had equivocal reactions on immunofluorescence assay (IFA). We conclude that the RIBA-HIV216 is approximately as sensitive as and significantly more specific than virus-derived Western blot and IFA. The RIBA-HIV216 also allows for semiquantitation of specific antibodies that may be of value in clinical staging and therapeutic monitoring. PMID- 1899952 TI - Molecular and cellular aspects of T-lymphocyte responses to antigen. PMID- 1899953 TI - The Rh haplotype D--identified in five Cape colored families. PMID- 1899954 TI - [Methods for ensuring correct tracheal intubation. A review]. AB - To confirm correct intubation of the trachea, the literature mentions the following methods: Auscultation of thorax, the sensation of normal ventilation, gastric and thorax movement, condensation of water vapor in the tube lumen, external palpation on the patient's neck of the tube and the cuff, tactile palpation through the patient's mouth of the tube, x-ray of thorax and detection of hemoglobin oxysaturation with pulse oximetry. These methods can be used, but cannot be recommended, because they are not reliable. The following methods are recommended in the literature as reliable: Repeated laryngoscopy when there are direct visualization of the vocal cords, fiberoptic bronchoscopy, suction on the tube with a 60-ml syringe, auscultation of the upper abdomen and lungs and end tidal carbon dioxide measurement. For the daily routine, control, of the endotracheal tube placement, by auscultation over the epigastrium, then in the right and left axilla, and continuous measurement of carbon dioxide in the expired air are recommended. PMID- 1899955 TI - The microvasculature of the 7,12-dimethylbenz(a)anthracene (DMBA)-induced rat mammary tumour. I. Vascular patterns as visualized by scanning electron microscopy of corrosion casts. AB - We examined the microvasculature of the 7,12-dimethylbenz(a)anthracene (DMBA) induced rat mammary tumour by scanning electron microscopy of corrosion casts. An elaborate vascular envelope predominantly consisting of sinusoidal and venular vessels was formed around each tumour nodule. These vessels exhibited various abnormal features, whereas arterioles appeared normal. The abnormal vessels possessed many globular outpouches, possibly representing the site of angiogenesis. An additional capillary layer was seen in the marginal boundary between the tumour and host tissue. The lack of centrifugally extruding vessels in this layer may indicate a poor potency for vascular spread of tumour cells into the adjacent normal tissue. Loop-like or glomerular ingrowths were frequently found on the inner aspect of the vascular capsule, which eventually developed into a dense intranodular plexus. Intranodular vessels often showed focal narrowing, tapering and/or rupturing, possibly due to increased tissue pressure caused by proliferating tumour cells. Those surrounding necrotic portions were extremely dilated with occasional periodic varicosities. The features may be associated with the lessening of the tissue pressure resulting from tumour cell collapse. PMID- 1899957 TI - Histological grading and morphometric analysis of cartilaginous tumours. AB - Morphometric analysis of cartilaginous tumours was performed on 25 chondrosarcomas, 9 cases of enchondroma (ENCH), and 2 chondroblastic osteosarcomas (CBOS). The chondrosarcomas were classified into three grades of malignancy according to Evans' histological classification and were further divided into low and high grades of malignancy. Cellularity, nuclear area, binucleate cells and mitotic figures were examined using formalin-fixed and paraffin-embedded specimens. The cellularity was significantly higher in high grade chondrosarcoma (HGCS) than in low-grade chondrosarcoma (LGCS) (P less than 0.005). The nuclear area was larger in more malignant lesions. Significant differences in the nuclear area were found between ENCH and LGCS (P less than 0.005) and between LGCS and HGCS (P less than 0.01). Binucleate cells were found more frequently in LGCS than in ENCH (P less than 0.005). Although a few mitotic figures were found in HGCS, they were extremely rare in chondrosarcomas. Mitotic figures, however, were easily found in CBOS when compared with HGCS (P less than 0.05). These results suggest that nuclear area and binucleate cells are useful for differentiation between benign and malignant cartilaginous lesions and that easily detectable mitotic figures are a reliable marker for neoplastic cartilage in osteosarcoma. PMID- 1899956 TI - Arteriolosclerosis of the human renal allograft: morphology, origin, life history and relationship to cyclosporine therapy. AB - In the decade 1979-1988, 658 biopsies were collected from 568 cadaveric renal allografts. In 118 grafts a non-proliferative insudative vasculopathy (IVA) was found in afferent vessels. Immunosuppression was based on azathioprine (AZA) or on cyclosporin A (CsA), from 1983. The prevalence and extent of IVA has increased significantly since 1984. Light microscopy showed fibrinoid and hyaline masses of varying extent; transmural insudative "knobs", intimal oedema with metachromasia, and microthrombosis were also seen with CsA. The ultrastructure of the insudates was unremarkable but CsA grafts displayed early oedema and hypergranulation of endothelial cells with a disarray of smooth muscle cell (SMC) microfibrils, and pronounced degenerative changes of SMC. Rebiopsy showed stationary IVA in AZA grafts and progression in one-half of CsA-treated patients. Nephrectomy specimens revealed, however, a marked predominance of late rejection endarteritis; in only 3 cases was IVA and/or microthrombosis the possible cause of nephrectomy. The mean donor age was higher in severe IVA in CsA grafts and the mean post transplantation interval at the time of diagnosis of IVA was significantly shorter in CsA-treated patients. No important differences in cumulative graft survival were seen between grafts with absent, moderate or severe IVA. Unused cadaveric donors' kidneys of comparable age exhibited normal arterioles or a slight focal insudative or hyaline lesion. PMID- 1899958 TI - Immunodetection of sialyl-Tn antigen in normal, hyperplastic and cancerous tissues of the uterine endometrium. AB - The expression of sialyl-Tn antigen (STn) in normal, hyperplastic and neoplastic tissues of the uterine endometrium was examined by immunoperoxidase staining of formalin-fixed, paraffin-embedded samples using the monoclonal antibody TKH-2, directed toward the STn structure (NeuAc 2-6GalNac 1-O-serine or threonine). STn was expressed in 13 of 18 normal postovulatory endometria with an increasing staining intensity and incidence in the late secretory phase. It was consistently absent in 10 proliferative endometria. None of 5 cystic, 4 adenomatous or 12 atypical hyperplasias expressed STn, but areas of severe cytological atypia in 3 atypical hyperplasias showed faint expression. STn expression was detected in 36 of 43 adenocarcinomas. Although the extent of staining varied from a few to most of the cancer cells, general staining was observed throughout the cytoplasm of cancer cells with increased staining of the luminal surface and frequent positive staining of intraluminal mucin. Thus, it is clear that STn is selectively expressed in cancer cells and shows restricted expression in normal and hyperplastic endometrial tissues. STn may be an early marker of malignant transformation and has potential for use as a diagnostic aid in the surgical pathology of the uterine endometrium. PMID- 1899959 TI - Focal veno-occlusive lesions following metastasis of cancer in the liver with special reference to obstruction of lymphatics in hepatic veins. AB - Focal veno-occlusive lesions and congestion of the liver are found frequently at autopsy in patients with metastatic carcinoma in the liver. In 6 cases, intimal proliferation of loose connective tissue with dilatation of lymphatic capillaries was seen continuously from the terminal hepatic venule to the hepatic vein, and cancer cells were found only in lymphatic capillaries in the wall of the hepatic vein. In 7 cases, cancer cells infiltrated directly into the adventitia of the sublobular vein and intimal proliferation of loose connective tissue with or without formation of recent thrombi was observed. A main causative factor of hepatic veno-occlusive disease is thought to be leakage of plasma due to endothelial injury to the terminal hepatic venule and sublobular vein. Lymphatic obstruction, in addition to a direct reaction to invasion of cancer cells to the vessel wall, may also cause veno-occlusive lesions due to stasis and leakage of lymph fluid into the intima of the terminal hepatic venule, sublobular vein and hepatic vein. PMID- 1899961 TI - Degeneration of the corticopontine tract in olivopontocerebellar atrophy. AB - Nine cases of sporadic olivopontocerebellar atrophy [Dejerine-Thomas type, multisystemic atrophy (MSA)] were examined histologically and electron microscopically with special reference to the corticopontine tract. Five of nine cases showed degeneration of the myelinated nerve fibres in this tract. More severe degeneration of the fibres at the level of the pons than the crus cerebri indicates that degeneration of the fibres may start axodistally. Electron microscopy revealed selective involvement of large fibres in olivopontocerebellar atrophy, in contrast to unselective axonal atrophy in dentatorubropallidoluysian atrophy. The problem whether the degeneration of the tract is primary or secondary due to the loss of the pontine neurons remains open. We believe the former to be most likely. Degeneration of the corticopontine fibres should be added to the list of neuropathological findings in sporadic olivopontocerebellar atrophy. PMID- 1899962 TI - Evaluation of different mixing study reagents and dilution effect in lupus anticoagulant testing. AB - Until recently, the laboratory identification of lupus anticoagulants (LA) was not considered important. Often LA were regarded as a nuisance, resulting in factor assays and other coagulation tests with inconclusive results. However, the recognition of important clinical complications associated with the presence of LA has resulted in an emphasis on the detection of this phospholipid-dependent inhibitor. Most studies have evaluated the sensitivity of various screening or confirmatory procedures used in establishing the diagnosis of LA. The authors have focused on the variables involved in the mixing studies used to identify the presence of a circulating inhibitor. To detect the latter, attention to the ratio of patient plasma to normal plasma is important, particularly in the case of a minimally prolonged APTT. Also the source of "normal" plasma must be platelet poor to maximize sensitivity in the case of a weak LA. PMID- 1899963 TI - Changes in plasma levels of tissue-plasminogen activator/inhibitor complex and active plasminogen activator inhibitor in patients with disseminated intravascular coagulation. AB - Plasma levels of tissue-plasminogen activator.plasminogen activator inhibitor (t PA.PAI) complex and active PAI were assayed in 58 cases of disseminated intravascular coagulation (DIC). A significant elevation of both parameters was observed in most cases of DIC, especially in patients with non-Hodgkin lymphoma, sepsis, or some patients with acute leukemia, but no such elevation was observed in patients with acute promyelocytic leukemia (APL). The levels of both parameters were higher in cases of DIC with multiple organ failure (MOF) than in those without MOF. Since no elevation of t-PA.PAI complex was observed in most cases of APL, t-PA did not seem to play an important role in the activation of fibrinolytic system in APL. Active PAI, which reflects the inhibitory regulation in fibrinolytic system, was considered to play a role in the progression of MOF. Plasma levels of active PAI were low in the cases of APL, which had no complication of MOF. PMID- 1899960 TI - Megakaryocytopoiesis in haematological disorders: diagnostic features of bone marrow biopsies. An overview. PMID- 1899964 TI - EDTA-dependent pseudothrombocytopenia: a clinical study of 18 patients and a review of the literature. AB - EDTA-dependent pseudothrombocytopenia (EDTA-PTCP) is the phenomenon of a spurious low platelet count due to the appearance of antibodies that cause platelet agglutination in blood anticoagulated with EDTA. We review here the clinical features of 18 patients with EDTA-PTCP treated in our hospital from 1984 to 1987 as well as those of 34 patients reported in the literature. This phenomenon appears more frequently in severely ill patients, in association with autoimmune, neoplastic, atherosclerosis-related, and liver diseases. In the majority of our patients, EDTA-PTCP appeared during hospitalization, indicating that the antibody is an acquired one. Neither splenomegaly nor the presence of autoimmune markers were features of this entity. Unlike true thrombocytopenias, EDTA-PTCP is associated with a normal mean platelet volume. Awareness of this entity is essential since EDTA-PTCP is frequently misdiagnosed and therefore incorrectly treated. PMID- 1899965 TI - Platelet lipoxygenase defect (Wien-Penzing defect) in two patients with myocardial infarction. AB - In 2 male patients (35 and 38 years) presenting with myocardial infarction an abnormal conversion of exogenous 14C-arachidonic acid by the patients' platelets, incubated in vitro, was observed. Neither patient's platelets showed evidence of a lipoxygenase pathway. Platelet thromboxane formation from exogenous and endogenous substrate was high, while the platelet aggregation responses were normal. A myeloproliferative syndrome was excluded by bone marrow puncture. Similar defects have only been described so far in patients with myeloproliferative syndrome. This defect may be causative for the onset of clinical thrombotic events. It is speculative whether in vivo therapy with r-IFN alpha 1c might be able to eradicate the pathological platelet clone. PMID- 1899966 TI - Continuous infusion of monoclonal antibody-purified factor VIII. AB - Continuous intravenous infusion of wet and dry heat treated factor VIII products has been shown to be an effective, safe, and convenient alternative to pulse-dose therapy for the treatment of patients with hemophilia. We have used 12-hr, single bottle continuous infusion of a factor VIII product purified from plasma sources by the use of monoclonal antibodies (Monoclate; Rorer Pharmaceutical Company) for the treatment of four bleeding episodes in three patients with severe hemophilia A. Patients required 2.1 U/kg/hr to attain an in vivo factor VIII level of 50 U/dl. Clinical hemostasis was achieved for all treatment episodes and no untoward effects of therapy were noted. Stability of the factor VIII:C levels in the product in vitro was also demonstrated. We conclude from this preliminary data that continuous infusion of factor VIII products purified by monoclonal antibody technology is a safe, effective, and practical approach to the treatment of patients with hemophilia A. PMID- 1899967 TI - Tissue-plasminogen activator for pulmonary embolism resulting in shock: two case reports and discussion of the literature. AB - Two patients with significant relative contraindications to fibrinolysis, and with refractory shock caused by acute pulmonary embolism, who were successfully treated with recombinant tissue-type plasminogen activator (rt-PA) are reported. The role of rt-PA in the management of pulmonary embolism is discussed, and pertinent literature is reviewed. PMID- 1899968 TI - Spontaneous fractures of the long bones in nursing home patients. AB - Six long-term nursing home residents who experienced fractures of the long bones in the absence of obvious trauma are described. All patients had been essentially non-weight-bearing for at least 2 years before the episode. Four patients experienced fractures on more than one occasion. There was no evidence of physical abuse in any of these of patients; indeed, evidence against abuse was fairly good. Nonetheless, physical abuse was alleged by the patients' families in four of the cases. Long bone fracture in the absence of trauma in patients after prolonged bed rest has been well described in the radiologic and orthopedic literature, but not previously in geriatrics. It is important that this phenomenon be recognized, lest all unexplained fractures in nursing home patients automatically be taken as evidence of abuse or neglect. PMID- 1899970 TI - Regulation of parathyroid hormone secretion by plasma calcium in aging rats. AB - Plasma immunoreactive parathyroid hormone (irPTH) levels increase with aging. This study determined 1) whether NH2-terminal irPTH secretory responses to induced hypocalcemia differ between adult (6-mo-old) and aged (24- to 26-mo-old) male rats and 2) whether a higher set point for irPTH release by Ca is responsible for the elevated irPTH levels with aging. Basal irPTH levels were 68% higher and 1,25-dihydroxyvitamin D3 levels were 44% lower in aged rats. An acutely induced, constant hypocalcemic stimulus [0.32 mM decrement in ionized Ca (Ca2+) for 2 h] was developed in catheterized conscious adult and aged rats by ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) infusion using the Ca clamp technique. The initial irPTH secretory response to acute hypocalcemia (5-10 min) was reduced in aged rats (1.9- vs. 3.1-fold increase), suggesting reduced hormone stores. However, higher sustained irPTH levels (30 min to 2 h) were maintained in aged rats, indicating increased irPTH synthesis and release. The EGTA infusion rate necessary to maintain constant hypocalcemia was less in aged rats, suggesting skeletal resistance to PTH. Slow EGTA and Ca infusions were used to determine irPTH secretion at plasma Ca2+ levels from 0.7 to 1.5 mM. In aged rats, irPTH levels were higher at all Ca2+ concentrations, but the set point for irPTH release by Ca2+ was the same as in adult rats. Thus the elevated irPTH secretion in aged rats is not caused by a change in the set point for irPTH release but does result in decreased irPTH stores. PMID- 1899969 TI - Ca2+ channel blockers distinguish between G protein-coupled pharmacomechanical Ca2+ release and Ca2+ sensitization. AB - The effects of Ca2+ channel blockers on two modes of G protein-mediated pharmacomechanical coupling, Ca2+ release and modulation of Ca2+ sensitivity of the contractile apparatus, were investigated. Smooth muscles were permeabilized with Staphylococcal alpha-toxin or with beta-escin to avoid effects due to block of sarcolemmal Ca2+ channels, while retaining receptor/G protein coupling. In permeabilized portal vein smooth muscle, verapamil and nifedipine inhibited Ca2+ release induced by an alpha 1-adrenergic agonist (phenylephrine) and by guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S), but not that induced by inositol 1,4,5 trisphosphate (InsP3). These Ca2+ channel blockers also did not block the phenylephrine- or GTP gamma S-induced force development at constant cytoplasmic Ca2+ ("Ca2+ sensitization"). An alpha 1-blocker (prazosin) inhibited both the Ca2(+)-releasing and Ca2(+)-sensitizing effects of phenylephrine, but not those of GTP gamma S, nor did it block InsP3-induced Ca2+ release. We conclude that Ca2+ channel blockers selectively uncouple the Ca2(+)-releasing, but not the Ca2(+)-sensitizing, component of pharmacomechanical coupling. These findings raise the possibility that pharmacomechanical Ca2+ release may be modulated by dihydropyridine binding proteins at the level of G proteins/phospholipase C and also indicate a divergence of the Ca2(+)-releasing and Ca2(+)-sensitizing effects at some step prior to phospholipase C. PMID- 1899971 TI - Decreased thermogenic response to food with intragastric vs. oral feeding. AB - To examine the effects of sensory stimulations associated with eating on postprandial energy expenditure, thermogenic response to food (TRF) was measured in nine subjects after ingestion of a test meal and after intragastric injection of the same pureed meal through a nasogastric tube. A third measure was made after ingestion of water and a fourth after chewing the meal without deglutition. Each measurement lasted 6 h. Intragastric injection of the meal elicited a lower TRF than oral ingestion in every subject, and this difference was seen whether TRF was calculated from the pretest energy expenditure (PTEE) or from energy expenditure measured after water ingestion (EEW) (175 +/- 57 vs. 83 +/- 32 and 209 +/- 68 vs. 106 +/- 45 kJ for PTEE and EEW, respectively; P less than 0.05 for each test). In both tests, changes in respiratory quotient, plasma glucose, and insulin were similar. Sensory stimulation by the meal without deglutition did not induce a significant change in energy expenditure. These results suggest that TRF has two components in humans, one of which is dependent on preabsorptive sensory stimulations. Lack of change in substrate oxidations between oral and intragastric feeding suggests that TRF related to preabsorptive stimulations does not depend on the preferential use of fatty acids or glucose as a source of fuel. PMID- 1899972 TI - Modulation of the migrating myoelectric complex by brain noradrenergic systems in rats. AB - The respective role of central and peripheral noradrenergic systems in the control of migrating myoelectric complex (MMC) was investigated in rats following lesions with 6-hydroxydopamine (6-OHDA). 6-OHDA was injected via intraperitoneal (ip), intracisternal (icis), and intracerebroventricular (icv) routes in rats. Control animals received the vehicle alone. One month later, MMC was recorded in conscious rats chronically fitted with electrodes. The MMC period was significantly lengthened after 6-OHDA ip or icv injection, and slightly shortened after 6-OHDA icis injection. No disruption of central noradrenergic systems was detected after ip lesions. Norepinephrine content was reduced in the digestive tract after ip lesions, in the spinal cord after icis lesions, and in the cortex, the hypothalamus, pons-medulla, and the spinal cord after icv lesions. After icis lesions, noradrenergic perikarya were spared in pons-medulla, whereas only pons noradrenergic perikarya were lesioned after icv lesions. We conclude that lesions of brain noradrenergic systems modify MMC periodicity in rats. The rostral noradrenergic systems may play the major modulatory role. PMID- 1899973 TI - The molecular biology of mammalian arachidonic acid metabolism. AB - The metabolism of arachidonic acid by cyclooxygenase and lipoxygenase enzymes results in a wide range of oxidized products with potent biological activities. These metabolites, which include the prostaglandins and leukotrienes, have been implicated in the pathogenesis of a variety of inflammatory diseases. Research over the last decade has focused primarily on the elucidation of the chemical structure of the metabolites and their biological effects in vitro and in vivo. Recently, research on the enzymes that produce these bioactive metabolites through oxidization of arachidonic acid has intensified. Recombinant DNA techniques have enabled investigators to determine the nucleotide sequences for several of the enzymes in the arachidonic acid cascade. The resulting cDNAs are now being used to further investigate the biochemical and biological features of arachidonic acid metabolism. The purpose of this paper is to review how the cDNAs for these enzymes were obtained, what information they convey, and how they are being applied in current research. PMID- 1899974 TI - Heterogeneity of intact granules purified from canine mastocytoma cell lines. AB - We investigated the observation that some mast cells exhibit asynchronous release of granule-associated neutral proteases. Intact mast cell granules were isolated, purified, and studied with respect to their histamine, neutral protease, and proteoglycan content. Studies of two canine mastocytoma cell lines demonstrated differences in storage and packaging of granules within one of the cell lines (G) with respect to the neutral proteases and density, resulting in two distinct subpopulations of granules. By use of identical techniques no such differences were found in the other cell line (BR). These observations suggest that granule subpopulations in some mast cells may have a role in the differential release of mediators. PMID- 1899975 TI - Effects of P. aeruginosa-derived bacterial products on tracheal ciliary function: role of O2 radicals. AB - The purpose of this investigation was to evaluate the effects of bacterial products derived from Pseudomonas aeruginosa on the function of airway cilia and to assess the role of phagocytes and oxygen radicals in the observed responses. Ciliary beat frequency (CBF) was measured in a perfusion chamber with a microscopic technique using tracheal epithelial cells obtained from normal sheep by brush biopsy (70% epithelial cells, 18% macrophages, 11% neutrophils). Baseline CBF ranged between 678 and 1,126 min-1. After 20 min of perfusion with the cell free supernatant of P. aeruginosa culture (mucoid strain), a concentration-dependent depression of CBF was observed with a 58% inhibition at a 1:1 dilution (P less than 0.05). The P. aeruginosa-derived products pyocyanin and 1-hydroxyphenazine also decreased CBF in a dose-related fashion. The cilion inhibitory effects of the supernatant and bacterial products were markedly attenuated after centrifugation of the brush preparation (80% epithelial cells, 16.5% macrophages, 3.5% neutrophils). Glucose/glucose oxidase also caused a rapid, concentration-dependent cilioinhibition or ciliostasis. Catalase blocked or attenuated the ciliary effects of the supernatant, bacterial products and glucose/glucose oxidase. Thus bacterial products released from P. aeruginosa impaired ciliary activity by a pathway which involved neutrophils and was mediated by toxic oxygen radicals. PMID- 1899976 TI - Effects of inhibitors of EDRF and EDHF on vasoreactivity of perfused rat lungs. AB - Recent studies indicate that the endothelium of isolated rat pulmonary arteries releases two different factors, endothelium-derived relaxing factor (EDRF) and hyperpolarizing factor (EDHF), which participate in histamine- and acetylcholine induced relaxation. There is evidence for EDRF vasoreactivity in perfused lungs, but a role for EDHF, which hyperpolarizes vascular smooth muscle by activating membrane K+ channels, has not been reported. We used the inhibitors of EDRF, 20 microM hemoglobin, 200 microM NG-mono-methyl-L-arginine, and 2 mM L-canavanine, the nonselective blocker of K+ channels, 10 mM tetraethylammonium (TEA), and the inhibitor of ATP-sensitive K+ channels, 20 microM glibenclamide, to compare the roles of EDRF and EDHF in the vasoregulation of meclofenamate-treated, salt solution-perfused rat lungs. The three EDRF inhibitors had little or no effect on baseline perfusion pressure, but each potentiated the peak pressor response to airway hypoxia. Neither of them inhibited the pulmonary vasodilation to 5 microM histamine. TEA, but not glibenclamide, increased baseline pressure and potentiated the peak hypoxic response. Both K+ channel blockers, but not the EDRF inhibitors, also prolonged the hypoxic response by reducing the rate of spontaneous vasodilation. TEA, but not glibenclamide, inhibited histamine vasodilation. These results suggest roles for both EDRF and EDHF in the control of rat pulmonary vascular reactivity. EDRF is apparently not responsible for the low vascular tone of the normoxic lung and does not mediate the vasodilation to histamine, but it does modulate the hypoxic pressor response. The exact role of EDHF is uncertain, but it may also modulate hypoxic vasoconstriction and mediate at least part of the histamine vasodilation. PMID- 1899977 TI - Isolated MTAL cells produce an inhibitor of ouabain-sensitive oxygen consumption. AB - Dispersed medullary thick ascending limb (MTAL) cells of the rabbit kidney produce an inhibitor of transport-related oxygen consumption when incubated at 37 degrees C. Appearance of this inhibitor is enhanced by incubation with arachidonic acid. Its appearance can be prevented by either 10(-6) M nordihydroguaiaretic acid or 10(-4) M indomethacin, but not by 10(-6) M indomethacin. These results suggest that the transport inhibitor is an eicosanoid produced by a pathway other than that catalyzed by cyclooxygenase. It inhibits ouabain-sensitive respiration in intact cells treated with amphotericin, suggesting direct inhibition of the Na(+)-K(+)-ATPase. PMID- 1899978 TI - Kinetics of circulating vasopressin uptake by choroid plexus. AB - Uptake of circulating arginine vasopressin (AVP) by choroid plexus was studied by means of the in situ brain perfusion technique in anesthetized guinea pig and by means of single-circulation paired-tracer dilution technique in isolated perfused sheep choroid plexus. Kinetic analysis revealed saturable AVP uptake with Michaelis constant (Km) values of 32 +/- 4 and 31 +/- 5 nM and maximal saturable influx rate (Vmax) of 0.45 +/- 0.06 and 12.1 +/- 0.67 pmol.min-1.g-1 in guinea pig and sheep choroid plexus, respectively. The peptide fragments AVP-(1-8) and [pGlu4,Cyt6]AVP-(4-9), the amino acids L-phenylalanine, L-tyrosine, and 2 aminobicyclo(2,2,1)heptane-2-carboxylic acid, and the aminopeptidase inhibitors Bestatin and bacitracin did not influence hormone kinetics. However, the V1 antagonist [(1-beta-mercapto-beta,beta-cyclo-pentamethylenepropionic acid)-O methyl-Tyr2]AVP significantly inhibited AVP uptake with inhibitor constant (Ki) values of 0.19 +/- 0.03 (guinea pig) and 0.07 +/- 0.01 microM (sheep). The V2 agonist 1-desamino-8-D-AVP and pressinoic acid produced weak inhibitions only in guinea pig choroid plexus, and Ki/Km ratios indicated 220 and 310 times lower affinities than for AVP, respectively. It is suggested that the membrane mechanism responsible for AVP uptake in choroid plexus has a binding site with properties similar to those of V1 receptor. PMID- 1899979 TI - Differential effects of dietary fish oil on myocardial prostaglandin I2 and thromboxane A2 production. AB - Marmoset monkeys (Callithrix jacchus) were maintained for 24 mo on a standard primate diet [reference (Ref) diet] or this diet supplemented (8% wt/wt) with either sheep fat (SF), sunflower seed oil (SSO), or tuna fish oil (TFO). The polyunsaturated fatty acids (PUFA) of myocardial phospholipids demonstrated significant alterations as a result of the dietary (n-3) or (n-6) lipid supplementation. The reduction (P less than 0.05) in prostaglandin (PG) I2 in PUFA diet-fed groups (SSO, 113.8 +/- 7.8; TFO, 87.9 +/- 8.2 compared with Ref, 153.9 +/- 7.4 pg/mg dry wt) seems to be due to the rate limitation of the endogenous substrate, because the addition of exogenous arachidonic acid (AA) has obliterated the dietary difference. However, AA did not increase the basal PGI2 production in the Ref or SF dietary groups, which differed from that for thromboxane (Tx) A2 where 2- to 5-fold stimulation was observed. It is suggested that there exists a preferential channeling mechanism to direct AA derived from phospholipase hydrolysis of membrane phospholipids toward PGI2 synthesis. Conversely, the bulk of the AA for TxA2 biosynthesis appears to be supplied by a cytosolic nonesterified fatty acid pool. The effective replacement of AA of this pool and a specific inhibition of TxA2 synthetase enzyme complex by the (n-3) PUFA of fish oil are offered as likely mechanisms for the greater inhibition of TxA2 compared with PGI2 production observed in the present and previous studies. The present data on myocardial eicosanoids correlate well with the beneficial qualities of (n-3) and (n-6) dietary PUFA on cardiac function that we have reported previously. PMID- 1899980 TI - Delayed rectifier outward K+ current is composed of two currents in guinea pig atrial cells. AB - The delayed rectifier outward K+ current (IK) was studied in isolated guinea pig atrial myocytes using the whole cell voltage-clamp technique. Similar to previous findings in ventricular cells, IK of atrial cells is the composite of two distinct components: IK,r, a rapidly activating current that exhibits strong inward rectification and IK,s, a slowly activating current with only modest rectification. IK,r was defined by its sensitivity to block by Co2+ and the class III antiarrhythmic agent, E-4031. IK,r underlies the prominent outward "hump" (between -30 and +40 mV) in the steady-state current-voltage relationship. Activation of IK,r was not dependent on transient changes in intracellular Ca2+ concentration. Block of Ca2+ current by nisoldipine or nitrendipine did not prevent activation of IK,r. Peak IK,r was not decreased in cells when intracellular Ca2+ was strongly buffered with 1,2-bis(aminophenoxy)ethane N,N,N',N'-tetraacetic acid. The activation curve for IK,r in atrial cells had a threshold of -40 mV, a half-point of -19 mV, and a slope factor of 5.2 mV. The activation curve for IK,s had a half-point of +24 mV and a slope factor of 15.7 mV. The peak tail currents of fully activated IK,s (21.1 pA/pF) and IK,r (2.53 pA/pF) are about two times that previously measured in guinea pig ventricular cells. This difference in current density may partly explain why action potentials of atrial cells are shorter than those of ventricular cells in guinea pig hearts. PMID- 1899981 TI - Cysteine proteinase inhibitor in eccrine sweat is derived from sweat gland. AB - Although cysteine proteinases have been reported to be present in human eccrine sweat, their endogenous inhibitors, cysteine proteinase inhibitors (CPIs), have remained unstudied. We now present evidence that CPIs are indeed a true ingredient of human eccrine sweat. Sweat induced in sauna was collected over a Vaseline barrier placed on the skin to minimize epidermal contamination. The absence of major epidermal contamination of the sweat was further ensured by monitoring an epidermal marker, high-molecular-mass aminopeptidase. Sweat CPI was purified sequentially by chromatography with Sephacryl S-200, carboxymethylated papain-Sepharose, and anion-exchange Mono Q fast-protein liquid chromatography columns. Sweat CPI has a molecular mass of approximately 15 kDa, is stable for temperature (up to 80 degrees C) and pH (from 3 to 10), and inhibits papain, ficin, and sweat cathepsin B- and H-like enzymes. Sweat CPI may be of sweat gland origin because 1) the rate of CPI output in sweat (CPI concentration x sweat rate) is constant over 45 min; 2) antibody against epidermal CPI, which cross reacts with sweat CPI, localized immunoreactivity in the sweat duct; 3) CPI activity was present in the glandular extracts of control and methacholine stimulated (for 1 h in vitro) human sweat glands; and 4) the peaks of CPI activity in the glandular extract and sweat CPI were both eluted (by high pressure liquid chromatography) at around 15 kDa. Sweat CPI may be very similar to epidermal CPI (which belongs to the stefin family of CPIs) because of many shared characteristics. The identity and function of sweat CPI remain to be studied. PMID- 1899982 TI - Chemical regulation of cerebral blood flow in turtles. AB - This study was performed to test the effect of the chemical composition of the blood on cerebral blood flow (CBF) regulation in turtles. The CBF response to increases in arterial PCO2 (PaCO2) (hypercapnia) was measured during normoxia and anoxia in anesthetized freshwater turtles Pseudemys scripta. The radioactive microsphere technique was used to measure CBF. CBF increased with increases in PaCO2. The sensitivity of the CBF response to hypercapnia (delta CBF/delta PaCO2) was 0.68 ml.min-1.100 g-1. Torr-1 during normoxia. delta CBF/delta PaCO2 increased to 3.44 ml.min-1.100 g-1. Torr-1 during anoxia. The increases in CBF occurred at constant mean arterial blood pressure, which indicates that cerebral vascular resistance decreased. The increased CBF response during asphyxia (hypercapnia-anoxia) could be beneficial for survival during prolonged dives by increasing glucose delivery for brain anaerobic metabolism. In addition, increased CBF could aid in regulating brain acid-base composition by controlling extracellular fluid PCO2. PMID- 1899983 TI - Effect of glyceryl trinitrate and ice on dilation of hand veins. AB - Application of glyceryl trinitrate to a finger produced significant dilation of superficial hand veins. Gently rubbing ice over these veins for one minute slightly reduced this dilation, whereas rubbing ice over veins without glyceryl trinitrate caused significant venoconstriction. These results indicate that application of glyceryl trinitrate followed by local cooling may provide a simple and painless means of assisting venepuncture. PMID- 1899984 TI - Preliminary evaluation of a prototype tube-valve-mask ventilator for emergency artificial ventilation. AB - STUDY OBJECTIVE: The objective was to design a prototype tube-valve-mask ventilator that would permit relatively inexperienced operators to provide adequate emergency artificial ventilation, namely, adequate ventilatory volumes and a high oxygen and low carbon dioxide delivery. DESIGN: The tube-valve-mask ventilator is powered by the exhaled air of the operator and uses a tube to act as an oxygen reservoir (1,300 mL) that is filled between breaths. Mouth-to-mouth breathing was the standard against which the tube-valve-mask ventilator and the other accepted methods of mouth-to-mask and bag-valve-mask were assessed. SETTING: Comparison studies were conducted during simulated two-person CPR using a training mannikin equipped to measure ventilation volume and delivered oxygen and carbon dioxide concentrations. TYPE OF PARTICIPANTS: Seventeen volunteer first-year nursing students were used as operators. INTERVENTIONS: The order in which the pairs of operators performed each of the techniques was randomized. MEASUREMENTS AND MAIN RESULTS: The ventilation volume and the percentage of oxygen and carbon dioxide delivered by each technique were as follows (mean +/- SD): Mouth-to mouth (760 +/- 290 mL, 17 +/- 1% O2, 3.4 +/- 0.4% CO2), mouth-to mask (910 +/- 350 mL, 41 +/- 8% O2, 2.5 +/- 0.4% CO2), bag-valve-(soft) mask (550 +/- 230 mL, 94 +/- 3% O2, 0.03 +/- 0.02% CO2), bag-valve-(rigid) mask (560 +/- 300 mL, 96 +/- 3% O2, 0.03 +/- 0.02% CO2), and tube-valve-mask (860 +/- 290 mL, 91 +/- 7% O2, 0.2 +/- 0.2% CO2). CONCLUSION: In the hands of relatively inexperienced operators, mouth-to-mouth, mouth-to-mask, and tube-valve-mask techniques provide adequate ventilation volumes to a mannikin. This was not the case with the bag-valve-mask systems (800 mL; P = .05 by t test). Of the systems that provide adequate ventilation volume, the tube-valve-mask appears, superior in that higher oxygen and lower carbon dioxide concentrations can also be obtained (P = .05 by paired t test). PMID- 1899985 TI - Verification of endotracheal tube placement with colorimetric end-tidal CO2 detection. AB - STUDY OBJECTIVE: To determine the ability of a disposable colorimetric CO2 detector to accurately confirm or refute endotracheal tube placement. DESIGN: Two hundred fifty prospective emergency intubations. SETTING: Emergency intubations performed in the emergency department, helicopter, and prehospital ground environment. TYPE OF PARTICIPANTS: Intubations were performed by emergency medicine residents, paramedics, and flight nurses. INTERVENTIONS: The FEF CO2 detector was applied after 250 emergency intubations. Notation of color change indicating intratracheal placement was recorded in each case. Confirmation of refutation of the detector's results was determined subsequently through traditional methods. RESULTS: The sensitivity for confirmation of endotracheal intubation in the 137 patients with a palpable pulse was 100%. However, only 76 of 103 patients (sensitivity, 72%) in cardiac arrest had endotracheal intubation confirmed by color change. The device was uniformly specific for tracheal intubation in 73 arrested patients in whom a color change was noted (100%). There was one instance (of a total of seven misintubations) in which a positive color change was noted, but the tube was not intratracheal (specificity, 86%). Overall sensitivity for tracheal intubation was 88% (95% confidence limits; range, 0.83 to 0.92), and specificity for tracheal intubation was 92% (95% confidence limits; range, 0.62 to 0.99). CONCLUSION: The FEF colorimetric detector reliably detects intratracheal placement in the nonarrested patient. Its use in prolonged cardiac arrest merits further study. PMID- 1899986 TI - A disposable end-tidal CO2 detector to verify endotracheal intubation. AB - STUDY OBJECTIVE: We compared the performance of the Fenem FEF end-tidal CO2 detector with the TRIMED capnometer to verify endotracheal intubation. DESIGN: The FEF indicates the presence of CO2 by the color change of a chemically treated indicator; the TRIMED uses infrared technology. Both devices were used during 60 intubations. SETTING: Intubations during in-hospital emergency situations outside of the operating room were studied. TYPE OF PARTICIPANTS: Adult patients undergoing intubation for respiratory failure, CPR, and other airway protection situations were enrolled in the study. INTERVENTIONS: The TRIMED monitor and FEF detector were placed in series between the manual resuscitator and the patient's endotracheal tube adapter after endotracheal tube placement. MEASUREMENTS AND MAIN RESULTS: We defined the acceptable criterion for detection of CO2 as production of a positive signal within six manual resuscitator bag breaths. The TRIMED met this criterion in 58 of 60 patients (sensitivity, 0.97) and the FEF met this criterion in 59 of 60 patients (sensitivity, 0.98). A paired t test showed no statistically significant difference in performance between the two devices. In five of nine cases of intubation during CPR, the color change of the FEF was described as "subtle." In one CPR case, a positive signal was not obtained by either device. CONCLUSION: We conclude that the performance of the FEF CO2 detector is equal to that of the TRIMED monitor for verification of endotracheal intubation in nonCPR situations. Interpretation of FEF color changes during CPR should be approached with caution until further studies using the FEF during CPR are completed. PMID- 1899987 TI - Local cerebral glucose utilization in rats with petit mal-like seizures. AB - The quantitative 2-[14C]deoxyglucose autoradiographic method was applied to the measurement of local cerebral metabolic rates for glucose in a model of genetic petit mal-like seizures in a strain of Wistar rats. During the experimental period, epileptic rats exhibited synchronous spike-and-wave discharges recorded from the cerebral cortex, whereas the electroencephalographic pattern of control animals was normal. An overall consistent increase in local cerebral metabolic rates for glucose was observed in epileptic rats as compared to nonepileptic control rats. This increase was statistically significant in 52 of the 59 cerebral structures studied and concerned all cerebral functional systems. These results are in accordance with positron emission tomography measurements in humans with typical childhood absence epilepsy. There is a lack of anatomical correlation between areas demonstrating hypermetabolism and areas where spike-and wave discharges are recorded. Thus, the diffuse increase in cerebral energy metabolism in epileptic rats as compared to controls is not directly related to the occurrence of spike and wave discharges. PMID- 1899988 TI - Gastrointestinal blood flow velocity after the first feed. AB - Twenty preterm infants (gestational age range 27-36 weeks) who had never been fed enterally were studied. Doppler indices of flow velocity from the superior mesenteric and coeliac arteries were measured immediately before, and at postprandial time intervals up to 60 minutes after, a first feed of 1 ml of milk given through a nasogastric tube. There were no significant differences between the preprandial and postprandial values of blood pressure, heart rate, oxygen and carbon dioxide tensions, and pH. The median peak systolic velocity (PSV) (55.9 cm/sec) and time average mean velocity (TAV) (10.6 cm/sec) before the feed at the superior mesenteric artery rose progressively and significantly to postprandial peaks of 88.5 cm/sec and 20.5 cm/sec at 45 minutes, respectively. Significant postprandial rises in the median PSV and TAV values at the coeliac artery were also observed, with a peak at 45 minutes. There were no significant correlations between blood flow velocity indices (preprandial or postprandial) and gestational age, postnatal age, conceptional age, or birth weight. We conclude that the first exposure of preterm babies to a small volume of milk feed is associated with postprandial changes in blood flow velocity consistent with an increase in blood flow in the superior mesenteric and coeliac arteries, although the mechanism of this response is uncertain. PMID- 1899989 TI - Evaluation of a taurine containing amino acid solution in parenteral nutrition. AB - Vaminolact, an amino acid solution containing taurine, was given to 15 sick newborn babies. They were compared with a group of 10 babies who received a solution that did not contain taurine (Vamin glucose). Efficacy and safety were evaluated by monitoring plasma amino acid patterns, growth patterns, nitrogen balance, and biochemical and haematological profiles. No serious abnormalities in amino acid concentrations were found. After an initial fall the taurine concentration recovered more rapidly in those receiving the taurine supplement, though this difference was not significant. Phenylalanine concentrations were within the reference range in the group receiving Vaminolact, and were significantly lower than in the group receiving Vamin glucose. Metabolic acidosis, which occurred in several subjects in each group, was not a serious problem. Liver function tests remained satisfactory. Nitrogen retention was greater among those receiving Vaminolact than in the control group. Vaminolact is a safe and effective amino acid solution for use in critically ill babies. PMID- 1899990 TI - Pulmonary intravascular lipid in neonatal necropsy specimens. AB - The lungs of 482 liveborn infants were examined at necropsy for the presence of intravascular lipid. Forty one patients had received parenteral feeding (including lipid emulsion in 30), and 441 had died before starting feeds or had received enteral feeds alone. Tissue was processed into wax and then stained with Sudan black; intravascular lipid was found in 15 of 30 infants who had received intravenous fat (Intralipid), but in no others. Those patients with positive lipid staining had received significantly more fat during parenteral nutrition than those in whom intravascular lipid was not found but the two groups were otherwise clinically indistinguishable. Using this staining technique intravascular lipid can be shown relatively often, although only in patients who have received intravenous lipid emulsion. The location of fat, predominantly in small pulmonary capillaries, and the absence of lipid emboli in other organs, suggests that lipid coalescence takes place before death and is not a postmortem artefact. The clinical relevance remains uncertain. PMID- 1899991 TI - Effects of mercury, selenium, and organochlorine contaminants on reproduction of Forster's terns and black skimmers nesting in a contaminated Texas Bay. AB - Mean mercury (0.40 micrograms/g), and geometric mean DDE (1.6 micrograms/g) and polychlorinated biphenyl (PCB) (2.3 micrograms/g) concentrations in Forster's tern (Sterna forsteri) eggs from Lavaca Bay were higher than those in tern eggs from a reference area in San Antonio Bay, but residues were not correlated with hatching success. Nest success was similar between bays. Selenium levels in Lavaca Bay tern eggs (0.71 micrograms/g) were also comparable to those in eggs from the reference area (0.68 micrograms/g). Clutch size (3.1 to 3.4) of Lavaca Bay black skimmers (Rynchops niger) was no different than that (3.4) at a reference colony near Laguna Vista. Nest success was similar among three Lavaca Bay colonies, but success was lower at one Lavaca Bay colony (40%) than at Laguna Vista (65%). Mean mercury (0.46 micrograms/g) and selenium (0.75 micrograms/g) concentrations in skimmer eggs from Lavaca Bay were higher than those (0.19, 0.33 micrograms/g) from Laguna Vista; however, concentrations of neither contaminant were related to hatching success. DDE concentrations in Lavaca Bay skimmer eggs (3.4 micrograms/g) were similar to those from Laguna Vista (3.2 micrograms/g) and DDE was negatively correlated with hatching success. PCBs were higher in eggs from Lavaca Bay (1.3 micrograms/g) than Laguna Vista (0.8 micrograms/g). Organochlorine and metal contaminants in most eggs were below embryotoxic levels. Eggshell thinning in Forster's terns (7%) and black skimmers (5%) was below that associated with lowered reproduction. DDE and PCBs were detected in 9 Caspian tern (S. caspia) eggs; maximum concentrations were 4.7 and 5.4 micrograms/g. Caspian tern and least tern (S. albifrons) eggs contained low (less than or equal to 0.9 micrograms/g) concentrations of mercury and selenium. PMID- 1899992 TI - Polychlorinated biphenyl congeners in blood of Wisconsin sport fish consumers. AB - As part of a study to evaluate the effect of chemical contaminants on Wisconsin sport fish consumers, measurements were made of polychlorinated biphenyl (PCB) congeners in human blood sera. A high resolution gas chromatography procedure was employed, with 13 individual congeners used as standards. Analytical recoveries and precision were greater than 90% and replicates were always within +/- 30%. Total concentrations, obtained by summing quantified congeners, ranged from 0.6 to 27.1 micrograms/L. Conventional packed column PCB analysis, conducted on a subset of samples, gave higher total PCB results. On a congener specific basis, congeners 153 (245-245), 138 (234-245), 180 (2345-245) and 118 (245-34) were found most often. These congeners have been reported to be prominent in other matrices. Of the congeners found, 118, 138, and possibly 180 are potentially the most toxic (based on current toxicological information). PMID- 1899993 TI - The biomagnification of polychlorinated biphenyls, toxaphene, and DDT compounds in a Lake Michigan offshore food web. AB - The biomagnification of polychlorinated biphenyls (PCB), toxaphene, and the DDT family of metabolites was investigated in the epibenthic Mysis relicta (mysid), the benthic Pontoporeia hoyi (amphipod), plankton, particulate flux, surficial sediments, and Myoxocephalus thompsoni (deepwater sculpin) in southeastern Lake Michigan. DDE was the most strongly biomagnified compound, increasing 28.7 times in average concentration from plankton to fish. PCB increased 12.9 times in average concentration from plankton to fish while toxaphene increased by an average factor of 4.7. Particle flux was comprised of lower chlorinated PCB homologues (average chlorine number = 3.8) than the biota (4.5-5.0) and sediments (4.6), possibly reflecting strong influences from atmospheric deposition and/or zooplankton egestion. The percent of higher chlorinated PCB homologues (5 and 6 chlorine atoms per PCB molecule) increased from 54-56% of the total PCB in plankton and M. relicta, to 61% in P. hoyi, to 74% in sculpins. Amphipods contained greater concentrations than mysids of PCB, DDT residues, and toxaphene, possibly reflecting differences in habitat (benthic vs epibenthic) and diet (detritus vs plankton). Based on estimates of average areal biomass and contaminant concentration, offshore Lake Michigan P. hoyi populations contain approximately 15.0 times as much toxaphene, 9.5 times as much total DDT, and 12.0 times as much PCB as the offshore M. relicta populations. Thus, amphipods may represent a greater reservoir than mysids for contaminant storage and subsequent recycling in offshore Lake Michigan. PMID- 1899994 TI - Epidermal growth factor-induced expression of c-fos is influenced by altered gravity conditions. AB - Epidermal growth factor (EGF) activates a well characterized signal transduction system in human A431 epidermoid carcinoma cells, which leads to rapid and transient expression of the c-fos proto-oncogene. In order to investigate the influence of altered gravity on EGF-induced signal transduction, we have studied the EGF-induced c-fos expression under simulated hypo- and hypergravity conditions. In this report we show that EGF-induced fos expression is decreased under simulated hypogravity conditions, while hypergravity has a stimulatory effect on EGF-induced fos expression. These results show that the EGF-activated signal transduction system is influenced by gravity, and that gravity exerts its effects already in the early phases of the signal transduction cascade. PMID- 1899995 TI - Ca2(+)-driven [3H]arachidonate release in electropermeabilized human platelets shows an absolute requirement for MgATP2-. AB - Addition of micromolar Ca2+ to electropermeabilized human platelets which had been pre-labelled with [3H]arachidonate causes release of 3H only when millimolar concentrations of a nucleoside triphosphate, e.g. ATP, are present in the incubation medium. Addition of millimolar Ca2+ in the absence of ATP, or preincubation with ATP before addition of micromolar Ca2+, fails to cause a significant increase in 3H release. Purine nucleotides are more effective than pyrimidine nucleotides in activating Ca2(+)-driven 3H release. This activation does not appear to involve phosphate transfer, since metabolically stable analogues of ATP, e.g. the beta gamma-imido analogue, are effective in promoting 3H release. PMID- 1899996 TI - A novel multifunctional metabolic pathway in a marine mollusc leads to unprecedented prostaglandin derivatives (prostaglandin 1,15-lactones). AB - The discovery of high levels of prostaglandin (PG) 1,15-lactones of both the E and F series and their co-existence with PGs has been recently described in the opisthobranch mollusc Tethys fimbria. The present study was undertaken in order to investigate the biosynthesis of these novel natural PG derivatives in vivo using radiolabelled precursors, and to gain a preliminary understanding of their biological role. PGE2 1,15-lactone was shown to be produced from both PGE2 and PGF2 alpha in the mollusc mantle and appeared to be quickly transferred to the mollusc dorsal appendices (cerata). The detachment of the latter during the typical defence behaviour of T. fimbria was accompanied by the conversion of PGE2 and PGE3 1,15-lactones back to the corresponding PGs. Both PGE2 and PGE2 1,15 lactone were also shown to be biosynthesized from arachidonic acid. Lactones of the F series were present as 11-acetyl derivatives in T. fimbria mantle and as 9- and 11-fatty acyl esters in the mollusc egg-mass and reproductive gland, and their biosynthesis from PGF2 alpha was demonstrated in all of these tissues. A multiple biological role of PG 1,15-lactones in T. fimbria defensive behaviour, smooth muscle contraction and egg production/fertilization control is hypothesized. The high amounts of PG derivatives found in T. fimbria and the biosynthetic studies described herein indicate that this marine mollusc may be a useful model for future studies on PG biosynthesis. PMID- 1899998 TI - A proton-magnetic-resonance study of hydrogen-exchange reactions of yeast tryptophan synthase. AB - 1H n.m.r. was used to observe tryptophan formation from indole and L-serine, proton exchange at C-2 of L-tryptophan, and proton exchange at C-2 of L-serine, catalysed by yeast tryptophan synthase in the presence of 2H2O. Tryptophan synthesis took place with compulsory replacement of C-2 hydrogen by solvent hydrogen. The exponential decay rate (kobs) of the serine exchange reaction was insensitive to serine concentration in the range 2-20mM and was used to calculate kcat./Km values. However, kobs. was very sensitive to pH* values in the range 6.5 8.5 and the data require that the free enzyme is active in the base form resulting from two inseparable ionizations of pKa 7.3, and inactive after a third ionization controlled by a pKa of 7.5. Initial rates measured by u.v. absorbance and colorimetric procedures were used to calculate kinetic parameters of the tryptophan synthesis reaction. From pH 6.5 to 7, kcat./Km values for L-serine in the tryptophan synthesis and hydrogen exchange reactions were indistinguishable and increased rapidly under the control of two acid-base groups of pKa 6.7 and 7.2. Above pH 7, this equivalence breaks down because the exchange reaction alone is responsive to the third pKa value of the free enzyme. The pH dependence of the catalytic constant for tryptophan synthesis was qualitatively similar to that of the kobs. for serine exchange. A mechanism to explain the results is contrasted with recent proposals for the Escherichia coli system. PMID- 1899997 TI - Copper-ion-dependent damage to the bases in DNA in the presence of hydrogen peroxide. AB - Mixtures of Cu2+ and H2O2 at pH 7.4 caused damage to the bases in DNA greater than that caused by mixtures of Fe3+ and H2O2. Addition of ascorbic acid to the Cu2+/H2O2 system caused a very large increase in base damage, much greater than that produced by the Fe3+/H2O2/ascorbic acid system. The products of base damage in the presence of Cu2+ were typical products that have been shown to result from attack of hydroxyl radicals upon the DNA bases. Cytosine glycol, thymine glycol, 8-hydroxyadenine and especially 8-hydroxyguanine were the major products in both the Cu2+/H2O2 and the Cu2+/H2O2/ascorbic acid systems. Base damage in DNA by these systems was inhibited by the chelating agents EDTA and nitrilotriacetic acid and by catalase, but not by superoxide dismutase, nor by the hydroxyl radical scavenger mannitol. It is proposed that Cu2+ ions bound to the DNA react with H2O2 and ascorbic acid to generate hydroxyl radicals, which then immediately attack the DNA bases in a site-specific manner. A hypoxanthine/xanthine oxidase system also caused damage to the DNA bases in the presence of Cu2+ ions. This was inhibited by superoxide dismutase and catalase. The high activity of Cu2+ ions, when compared with Fe3- ions, in causing hydroxyl-radical-dependent damage to DNA and to other biomolecules, means that the availability of Cu2+ ions in vivo must be carefully controlled. PMID- 1900000 TI - The potency of inducers of NAD(P)H:(quinone-acceptor) oxidoreductase parallels their efficiency as substrates for glutathione transferases. Structural and electronic correlations. AB - Induction of glutathione transferases (EC. 2.5.1.18), NAD(P)H:(quinone-acceptor) oxidoreductase (EC 1.6.99.2; quinone reductase) and other detoxification enzymes is a major mechanism for protecting cells against the toxicities of electrophiles, including many carcinogens. Although inducers of these two enzymes belong to many different chemical classes, they nevertheless contain (or acquire by metabolism) electrophilic centres that appear to be essential for inclusive activity, and many inducers are Michael reaction acceptors [Talalay, De Long & Prochaska (1988) Proc. Natl. Acad. Sci. U.S.A., 85, 8261-8265]. The inducers therefore share structural and electronic features with glutathione transferase substrates. To define these features more precisely, we examined the inductive potencies (by measuring quinone reductase in murine hepatoma cells) of two types of glutathione transferase substrates: a series of 1-chloro-2-nitrobenzenes bearing para-oriented electron-donating or -withdrawing substituents and a wide variety of other commonly used and structurally unrelated glutathione transferase substrates. We conclude that virtually all glutathione transferase substrates are inducers, and their potencies in the nitrobenzene series correlate linearly with the Hammett sigma or sigma- values of the aromatic substituents, precisely as previously reported for their efficiencies as glutathione transferase substrates. More detailed information on the electronic requirements for inductive activity was obtained with a series of methyl trans-cinnamates bearing electron withdrawing or -donating substituents on the aromatic ring, and in which the electronic densities at the olefinic and adjacent carbon atoms were measured by 13C n.m.r. Electron-withdrawing meta-substituents markedly enhance inductive potency in parallel with their increased non-enzymic reactivity with GSH. Thus, methyl 3-bromo-, 3-nitro- and 3-chloro-cinnamates are 21, 14 and 8 times more potent inducers than the parent methyl cinnamate. This finding permits the design of more potent inducers, which are important for elucidation of the molecular mechanisms of induction. PMID- 1899999 TI - Isolation and characterization of sheep alpha 1-proteinase inhibitor. AB - Sheep plasma proteinase inhibitor, analogous to human alpha 1-proteinase inhibitor (alpha 1 PI), was isolated to homogeneity. Purification was achieved by using (NH4)2SO4 precipitation, concanavalin A-Sepharose chromatography, Mono Q ion-exchange chromatography and PAGE. Sheep alpha 1 PI had an Mr of 56,000, inhibited human leucocyte elastase, pig pancreatic elastase and bovine trypsin on a 1:1 molar basis and had a plasma concentration of 1.6 +/- 0.21 g/l (mean +/- S.D.). Amino acid/carbohydrate composition (15% glycosylated) was similar to that of human alpha 1 PI (16% glycosylated); N-terminal analysis to 31 residues revealed 48-52% identity between the human and sheep proteins. Sheep alpha 1 PI was susceptible to oxidative inactivation by chloramine-T. Re-activation with the use of methionine sulphoxide peptide reductase and dithiothreitol indicated the presence of a methionine residue at the active site. These results establish that sheep alpha 1 PI has functional and structural characteristics close to those of human alpha 1 PI. PMID- 1900001 TI - Stoichiometric interaction of smg p21 with its GDP/GTP exchange protein and its novel action to regulate the translocation of smg p21 between membrane and cytoplasm. AB - We have previously purified a GDP/GTP exchange protein for smg p21A and -B, members of a ras p21/ras p21-like small GTP-binding protein superfamily. This regulatory protein, named smg p21 GDP dissociation stimulator (GDS), stimulates the dissociation of both GDP and GTP from and the subsequent binding of both GDP and GTP to smg p21s. We show here that smg p21 GDS forms a complex with both the GDP- and GTP-bound forms of smg p21B at a molar ratio of about 1:1. Both the GDP- and GTP-bound forms of smg p21B bound to membranes. smg p21 GDS inhibited this binding and moreover induced the dissociation of the prebound smg p21B from the membranes. These results indicate that smg p21 GDS stoichiometrically interacts with smg p21B and thereby regulates its GDP/GTP exchange reaction and its translocation between membranes and cytoplasm. PMID- 1900002 TI - Mitochondrial DNA mutation in a Chinese family with myoclonic epilepsy and ragged red fiber disease. AB - We analyzed the mitochondrial DNA of blood cells of 5 patients from a Chinese family with myoclonic epilepsy and ragged-red fiber disease. The results showed that in all the affected individuals there was a point mutation from A to G at the 8344th nucleotide pair, which was located in the tRNA(Lys) gene. No such a mutation was found in mtDNA of either unaffected members of that family or other healthy Chinese subjects. These findings are consistent with the recent report of Shoffner et al. (Cell 1990, 61: 931-937), and confirm that the point mutation is indeed the cause of this disease. PMID- 1900003 TI - Alternative, simultaneous complex I mitochondrial DNA mutations in Leber's hereditary optic neuropathy. AB - Leber's hereditary optic neuropathy has been linked to a mitochondrial DNA mutation at position 11,778 in the ND-4 gene in 50% of families. Three alternative mutations in Complex I genes at positions 4,216 (ND-1), 4,917 (ND-2), and 13,708 (ND-5) were discovered in 11,778- Leber families. The 4,917 and 13,708 mutations appear pathogenetically significant and were observed in 36% (4,917 mutation) and 43% (13,708 mutation) of 11,778- Leber probands. Multiple, simultaneous mutations were noted. Mutation of distinct, functionally related Complex I genes is the central pathogenetic feature of Leber's hereditary optic neuropathy. PMID- 1900004 TI - Effect of malathion on Bufo arenarum Hensel development--I. Esterase inhibition and recovery. AB - Newly fertilized Bufo arenarum Hensel embryos were exposed continuously or for a brief period (72-120 hr) to malathion (44 ppm) and then resuspended in amphibian Ringer's solution. Continuous exposure depressed acetylcholinesterase (EC 3.1.1.7), butyrylcholinesterase (EC 3.1.1.8) and carboxylesterase (EC 3.1.1.1) activities. The activities of the three enzymes in embryos treated for 72 hr recovered after a delay of 24 hr, but these enzymes showed different rates of recovery in embryos treated for 120 hr. Acrylamide disc electrophoresis showed several bands of esterase activity in control embryos. Continuous exposure to malathion abolished all esterase activity within 48 hr, but if the exposure continued new bands of esterase activity appeared at 120 hr of exposure. The zymograms of embryos exposed for 72 or 120 hr to malathion and then transferred to uncontaminated medium for 120 hr were similar to that of control embryos. PMID- 1900005 TI - Calcitriol-mediated modulation of urokinase-type plasminogen activator and plasminogen activator inhibitor-2. AB - Calcitriol-induced differentiation of U937 mononuclear phagocytes is known to have divergent effects on the synthesis of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor-2 (PAI-2). In this study, we sought to determine whether calcitriol affects the expression of these proteins by modulating intermediate signal transduction involving intracellular calcium and protein kinase C (PKC). U937 cells were stimulated with calcitriol (50 nM) for 6 72 hr, inducing a transient increase in specific binding of [3H]phorbol dibutyrate ([3H]PDBu), seen only after 24 hr. Staurosporine (2 nM), a PKC inhibitor, had no effect on calcitriol-induced secretion of plasminogen activator (PA) activity. However, staurosporine significantly (P less than 0.05) inhibited the ability of calcitriol to enhance phorbol myristate acetate (PMA)-induced secretion of PA inhibitor activity, indicating that this priming effect of calcitriol requires expression of PKC. The calcium ionophore A23187 (0.1 microM) induced a modest increase in secreted PA inhibitor activity, in contrast to the secretion of PA activity which is consistently seen in response to calcitriol. Northern blot analysis demonstrated that A23187 induced an increase in PAI-2 mRNA and a marked reduction in uPA mRNA, while calcitriol induced opposite changes in both mRNA species. We conclude that calcitriol modulates uPA and PAI-2 expression by multiple mechanisms that are both PKC dependent and PKC independent. Our studies also demonstrated that increased intracellular calcium alters the synthesis of both uPA and PAI-2 in a manner which favors expression of PA inhibitor activity. PMID- 1900006 TI - Induction of alkoxyresorufin O-dealkylases and UDP-glucuronosyl transferase by phenobarbital and 3-methylcholanthrene in primary cultures of porcine ciliary epithelial cells. AB - Our previous studies have shown that drug-metabolizing activities in the eye are highest in the ciliary body, a tissue responsible for aqueous humor production. In this work, we have separated nonpigmented epithelial (NPE) cells and pigmented epithelial (PE) cells from porcine ciliary body and determined basal and induced activities of 7-ethoxyresorufin (ER) O-dealkylase, 7-pentoxyresorufin (PR) O dealkylase, and UDP-glucuronosyl transferase (UDP-GT) using primary cultures of separated cells. ER and PR activities were associated primarily with NPE cells and were very low in PE cells. Treatment of NPE cells with phenobarbital (PB) for 48 hr resulted in about a 4-fold increase in PR O-dealkylase activity but only a 1.3-fold rise in ER O-dealkylase activity. Conversely, 3-methylcholanthrene (MC) treatment augmented the ER O-dealkylase activity of NPE cells 6 times over the basal activity in 48 hr but had little effect on PR O-dealkylase activity. Both NPE and PE cells had low basal UDP-GT activities. UDP-GT activity increased about 5-fold in PB-treated PE cells and about 4-fold in PB-treated NPE cells in 48 hr. The results of MC treatment were similar to those of PB treatment; enhancement of UDP-GT was more pronounced in PE cells than in NPE cells. Induction by PB and MC of ER O-dealkylase, PR O-dealkylase and UDP-GT activities in ciliary NPE and PE cells was inhibited almost completely by 3.5 microM cyclohexamide and 40 nM actinomycin D. The heterogeneous distribution of these enzymes suggests that a harmonious interplay between NPE and PE cells is important for metabolic detoxification of blood plasma prior to aqueous humor formation. PMID- 1900007 TI - Effect of early intravenous rt-PA on infarct size estimated from serum enzyme activity: results from the TEAHAT Study. AB - In 319 patients who participated in a double-blind trial to evaluate the effect of early rt-PA administration compared to placebo in suspected acute myocardial infarction, infarct size was assessed from analyses of serum activity of lactate dehydrogenase isoenzyme 1 (LD 1). Treatment was always started less than 3 h after the onset of symptoms, with one-third of the patients' treatment being initiated outside the hospital. The maximum activity of LD 1 was reduced by 32%, from 13.3 mu kat l-1 in placebo to 9.0 mu kat l-1 in rt-PA treated patients (P = 0.001). A reduction in LD-1 activity after rt-PA treatment was restricted to patients with ST-elevation in the initial electrocardiogram, and was more pronounced in patients with previous ischaemic heart disease, above median age, and in those with a shorter delay in initiation of treatment. We conclude that very early intravenous treatment with rt-PA limits indirect signs of infarct size. The effect appears to be restricted to patients with ST-segment elevation in their initial electrocardiogram. PMID- 1900008 TI - Early thrombolytic therapy in suspected acute myocardial infarction--role of the electrocardiogram: results from the TEAHAT Study. AB - In a placebo-controlled trial in which rt-PA was administered to patients within 2 h and 45 min after the onset of symptoms indicative of acute myocardial infarction (AMI), 352 patients were randomized. Standard 12-lead electrocardiograms (ECGs) were recorded at inclusion and repeatedly during admission and at follow-up after 1 month and 1 year. In patients who presented with ST-segment elevation, the infarction rate was high (88%), whereas in patients without ST-elevation the infarction rate was low (21%), and infarct size, as assessed by serum enzyme activities, was small in this group. There were only minor differences between rt-PA- and placebo-treated patients with regard to ST-segment changes and Q-wave development, whereas the R-wave amplitude was higher after 1 month in patients who were given rt-PA. The infarction rate was not altered by rt-PA, but there was a shift towards a reduction in Q-wave infarction in patients who were treated with rt-PA. When a score system, as suggested by Palmeri et al., intended to reflect the ultimate infarct size, was applied, a significantly lower score was found in infarction patients who were treated with rt-PA as compared to placebo (3.95 +/- 0.35 vs. 2.95 +/- 0.29, P = 0.03), indicating limitation of infarct size. In summary, early treatment with rt PA resulted in less frequent Q-wave infarction and a reduction in the electrocardiographically estimated infarct size. PMID- 1900009 TI - Effects on chest pain of early thrombolytic treatment in suspected acute myocardial infarction: results from the TEAHAT Study. AB - In a randomized, double-blind study, in which recombinant tissue plasminogen activator (rt-PA) administered at an early stage was compared with placebo in patients with suspected acute myocardial infarction (AMI), the effects on pain were studied in 312 patients. Inclusion criteria were as follows: (a) chest pain of duration less than 2 h and 45 min; and (b) age less than 75 years. Chest pain was estimated subjectively by the patients, using a 10-point numerical rating scale, at hourly intervals for the first 24 h, and by the requirement for narcotic analgesics. Compared with placebo, rt-PA treatment resulted in a 43% reduction in mean total pain score (P less than 0.0001), a 26% reduction in pain duration (P less than 0.01), and a 33% reduction in morphine requirement (P = 0.01). Fifty-seven per cent of all patients developed a confirmed AMI. In these subjects rt-PA reduced the pain score by 46% (P less than 0.001). Among patients without confirmed AMI, a 37% reduction in pain score was observed (P = 0.05). The effect on pain was most marked in patients with ST-elevation on the initial ECG. We conclude that early treatment with rt-PA in suspected AMI reduces chest pain considerably. The effect is most marked in patients with ST-elevation on the initial ECG. PMID- 1900010 TI - Prehospital thrombolysis in suspected acute myocardial infarction: results from the TEAHAT Study. AB - In a randomized, double-blind study, rt-PA vs. placebo treatment in early suspected acute myocardial infarction (AMI) was evaluated in patients both in hospital and prehospitally. The inclusion criteria were as follows: (a) age less than 75 years; and (b) chest pain indicative of AMI, of no longer than 2.75 h duration before first examination. In the prehospital setting a mobile coronary care unit, accompanied by a cardiologist, was sent out by the ambulance services to 350 patients, of whom 205 (59%) were classified as non-eligible when examined by the cardiologist. Of the 145 patients who fulfilled the inclusion criteria, 44 were excluded due to contraindications to thrombolytic treatment. Thus 101 patients were randomized to blinded treatment outside hospital. The median time interval between onset of pain and treatment was 75 min, 45 min less than for those subjects who were randomized in hospital. The prevalence of confirmed AMI was 42% in the prehospital group, compared to 66% in the hospital group. Bleeding and cardiac complications for prehospital treatment were few, and similar to those for hospital treatment. In conclusion, prehospital thrombolysis was feasible, and delay times prior to treatment were significantly reduced. However, the specificity and diagnostic accuracy were lower than those achieved with in hospital therapy. PMID- 1900011 TI - Early treatment with thrombolysis and beta-blockade in suspected acute myocardial infarction: results from the TEAHAT Study. AB - Independent trials of early administration of beta-blockers and thrombolytic agents have shown beneficial effects on both short- and long-term prognoses in acute myocardial infarction (AMI). The effects of a combination of the two strategies have not been thoroughly documented. Three hundred and fifty-two patients, of less than 75 years of age, with chest pain indicative of AMI, and onset less than 2 h and 45 min before first examination, were randomized to treatment with rt-PA or placebo. All patients without contraindication were given intravenous metoprolol 15 mg acutely and then 200 mg orally daily. Treatment was started either at the prehospital stage or in hospital. Thirty-seven per cent of patients had contraindications to beta-blockade, the most frequent of which were heart rate less than 60 beats min-1 and hypotension. The remaining 63% were given intravenous beta-blockade. No side-effects of metoprolol, alone or in combination with rt-PA, were observed during the prehospital phase. Overall, toleration of the treatment was good. Reduction in enzymatically estimated infarct size by rt PA was more pronounced in patients who were also treated with metoprolol (41%, P less than 0.001) than in those with contraindications to beta-blockade (15%, NS). Patients who were also treated with metoprolol also had a lower incidence of Q wave infarctions, congestive heart failure and ventricular fibrillation than those who were not given intravenous beta-blockade. In conclusion, toleration of intravenous administration of rt-PA and metoprolol was good, and this was also the case in the prehospital phase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1900012 TI - Mortality and morbidity 1 year after early thrombolysis in suspected AMI: results from the TEAHAT Study. AB - We randomized 352 patients with suspected acute myocardial infarction (AMI) to treatment with rt-PA (n = 177) or placebo (n = 175). Patients were eligible if evaluated within 2 h and 45 min from onset of chest pain, and if aged less than 75 years. There were no ECG criteria for inclusion. A mobile coronary-care unit with a cardiologist present was used to initiate treatment at home in 29% of cases. During 1 year of follow-up the mortality in patients treated with rt-PA was 10.2%, as compared with 14.3% in patients the initial ECG, the mortality during the first year was 8% in the rt-PA group vs. 18% in the placebo group (P less than 0.05). Among patients without ST-elevation the mortality was 9% for the rt-PA group vs. 12% for the placebo group (NS). Requirement for rehospitalization, symptoms of angina pectoris and congestive heart failure, time of return to work and requirement for various medications did not differ significantly between the two groups, regardless of the initial ECG pattern. PMID- 1900013 TI - Interhospital transfer of a patient undergoing extracorporeal carbon dioxide removal. AB - Extracorporeal circulation techniques are being used increasingly in patients with acute cardiac or pulmonary failure. Some of these patients may subsequently require transportation, which has limited the use of these techniques in hospitals without on site transplantation facilities. We report a case of adult respiratory distress syndrome that demonstrates a solution to this problem. PMID- 1900015 TI - A dose of Glasnost: crossing the great divide. PMID- 1900014 TI - Effect of arterial carbon dioxide tension on the duration of action of atracurium. AB - The duration of action of atracurium was studied in two groups of patients. In group I (n = 15), patients' lungs were hyperventilated to a mean PaCO2 of 3.3 kPa and in group II (n = 15) lungs were ventilated to maintain a mean PaCO2 of 5.3 kPa. Anaesthesia was maintained using an infusion of propofol. The time taken to return to a T1 twitch height of 10% of control was measured following each incremental dose of atracurium 0.15 mg kg-1. It was found that the duration of action of atracurium was significantly (P less than 0.0005) shorter in the hypocapnic group. PMID- 1900017 TI - Crisis in the Gulf. Theatre of war. PMID- 1900018 TI - Nurses' prescription of stoma appliances. PMID- 1900016 TI - Volunteer reserves: nurses in reserve. Interview by Bob Peedle. PMID- 1900019 TI - Reducing violence in a special hospital. PMID- 1900020 TI - Surveillance of hospital infection. PMID- 1900021 TI - ECG file. Supraventricular and ventricular tachycardia. PMID- 1900023 TI - Ageing demand for care. PMID- 1900024 TI - Coping with the guilty ill. PMID- 1900022 TI - Computing: an aid to studying nursing. PMID- 1900025 TI - New Year's resolution to care. PMID- 1900026 TI - AIDS focus. The challenge for nurses. PMID- 1900027 TI - AIDS focus. Changing times. PMID- 1900028 TI - AIDS focus. Getting the message. PMID- 1900029 TI - Effect of the leafy vegetable Solanum nigrum on the activities of some liver drug metabolizing enzymes after aflatoxin B1 treatment in female rats. AB - Wistar albino female rats were maintained for 10 d on diets containing various levels of the vegetable Solanum nigrum. Simultaneously, they received daily intraperitoneal injections of aflatoxin B1 (AFB1) (either 0.2 or 0.4 mg/kg body weight) diluted in propylene glycol. At the end of the experiment, all animals were killed and their serum and hepatic microsomes were prepared for assay of enzymes. Results showed that aminopyrine N-demethylase activity increased 2.5 fold with 200 (S200) and 600 (S600) g S. nigrum/kg diets. Activity of uridine diphosphate glucuronyltransferase (UDPGT) (EC 2.4.1.17) also increased twofold. Similar results were obtained with glutathione S-transferase (EC 2.5.1.18) activity which increased by 60% with diet S600. After AFB1 treatment, a general increase in the activities of the above enzymes was found, except for UDPGT in the group fed on diet S600. When rats were fed on the diet without S. nigrum, AFB1 induced an increase in alkaline phosphatase (ALP) (EC 3.1.3.1), aspartate aminotransferase (AST) (EC 2.6.1.1) and gamma-glutamyltransferase (gamma-GT) (EC 2.3.2.2) levels in the serum. AFB1 also induced increases in serum ALP and gamma GT levels when rats were fed on diet S600. PMID- 1900030 TI - The impact of breast cancer on sexuality, body image, and intimate relationships. AB - For women, breast cancer remains a common and dreaded experience. It is normal for a diagnosis of breast cancer to evoke grief, anger, and intense fear. Most women, however, face this crisis and master it without developing major psychiatric disorders or severe sexual dysfunction. The options of breast conservation and reconstruction give women a new sense of control over their treatment and are quite successful in helping women feel comfortable with their bodies again. The effectiveness of breast conservation and reconstruction in preventing or ameliorating sexual problems after breast cancer diagnosis is less clear, however. Any impact these options have on sexuality is subtle and may relate more to a woman's feelings of being desirable than to how often she has sex, her lovemaking practices, or how much she enjoys sex. We need more information on how chemotherapy and hormonal therapy affect women's sex lives. As clinicians, we should pay more attention to our patients' complaints of vaginal pain, dryness, and overall loss of sexual desire during systemic treatment. Practical advice on lovemaking techniques and a clinician's open attitude towards discussing sexual issues can prevent a great deal of anxiety and sadness as women with breast cancer search for ways to keep their sex lives satisfying. PMID- 1900031 TI - Staging of cancer. PMID- 1900032 TI - Unproven methods of cancer management. Fresh cell therapy. PMID- 1900033 TI - Breast cancer: change and challenge. PMID- 1900034 TI - The surgical management of primary breast cancer. PMID- 1900035 TI - The role of radiation therapy in the management of primary breast cancer. PMID- 1900036 TI - Integrated software. A valuable long term care nursing tool. PMID- 1900037 TI - Reduced tumorigenicity of murine tumor cells secreting gamma-interferon is due to nonspecific host responses and is unrelated to class I major histocompatibility complex expression. AB - Spontaneous SP1 murine adenocarcinoma cells transfected with the murine gamma interferon (IFN-gamma) gene expressed IFN-gamma (SP1/IFN-gamma) failed to grow in syngeneic hosts and grew in nude mice. The rejection of SP1/IFN-gamma cells was related to the amount of IFN-gamma produced and appeared to be mediated primarily by nonspecific cellular mechanisms, although some role for T-cells in the afferent arm of this response is possible. SP1 cells are H2-Kk negative but express class I antigens when producing IFN-gamma. However, class I major histocompatibility complex (MHC) expression, while likely necessary, was insufficient in itself to prevent tumor growth since secretion of greater than 64 units/ml IFN-gamma was needed to inhibit tumorigenicity while only 8 units/ml IFN gamma could induce class I antigens. Similar results were obtained with the murine colon carcinoma CT-26, a tumor that constitutively expresses class I MHC antigens, further supporting the contention that class I MHC expression is not essential for the rejection response induced by IFN-gamma. The failure of SP1/IFN gamma cells to protect against a challenge with parent SP1 cells argues that factors other than IFN-gamma production or class I MHC expression are needed to induce a protective response against weakly or nonimmunogenic tumor cells. PMID- 1900038 TI - Evidence for a common genetic pathway controlling susceptibility to mouse skin tumor promotion by diverse classes of promoting agents. AB - The present study has compared different mouse stocks and strains with known sensitivity to phorbol ester skin tumor promotion for their sensitivities to skin tumor promotion by a prototypic organic peroxide (benzoyl peroxide, BzPo) and anthrone (chrysarobin, Chr) tumor promoter. Following initiation with either 7,12 dimethylbenz(a)anthracene and/or N-methyl-N'-nitro-N-nitrosoguanidine, groups of mice were promoted with several different doses of each promoting agent. Among mice selectively bred for sensitivity to phorbol ester promotion, the order of sensitivity to BzPo was inbred SENCAR (SSIn) greater than SENCAR greater than CD 1. With Chr as the promoter, the order of sensitivity was SENCAR greater than SSIn greater than CD-1. Concurrent tumor promotion experiments examined the responsiveness of two common inbred mouse strains, DBA/2 and C57BL/6. The phorbol ester-responsive mouse strain, DBA/2, was more sensitive to skin tumor promotion by Chr than was C57BL/6 at all doses tested but was clearly less sensitive than both SENCAR and SSIn mice. Finally, DBA/2 and C57BL/6 mice were similar in their responsiveness to BzPo promotion, but again both of these inbred strains were significantly less sensitive than were SSIn and SENCAR mice to this organic peroxide type of skin tumor promoter. Histological evaluations comparing SENCAR and C57BL/6 mice revealed that a major difference between these strains in response to multiple Chr and BzPo treatments was in the inflammatory response (measured by edema formation). Unlike 12-O-tetradecanoylphorbol-13-acetate, Chr and BzPo did not induce dramatic differences in the epidermal hyperplasia (as measured by epidermal thickness) in these two mouse lines. The results presented in this paper suggest that there is a common pathway controlling susceptibility to skin tumor promotion by 12-O-tetradecanoylphorbol-13-acetate, BzPo, and chrysarobin. These results are discussed in terms of a possible genetic model(s) for skin tumor promotion in mice. PMID- 1900039 TI - Pheromone-induced phosphorylation of a G protein beta subunit in S. cerevisiae is associated with an adaptive response to mating pheromone. AB - The mating pheromone response in S. cerevisiae is activated by a G protein mediated signaling pathway in which G beta gamma is the active transducer of the signal. When exogenous pheromone is added to vegetatively growing cells, G beta is rapidly phosphorylated at several sites; phosphorylation does not require de novo protein synthesis. A mutation in G beta was constructed that eliminates signal-induced phosphorylation. This mutation leads to enhanced sensitivity to and impaired ability to recover from pheromone, but does not affect the ability of G beta gamma to transmit the mating signal. These phenotypes suggest that G protein phosphorylation mediates an adaptive response to pheromone-induced signaling. G beta phosphorylation does not require either the pheromone receptor C-terminus or the product of the SST2 gene, both of which mediate separate adaptive responses to pheromone. However, G beta phosphorylation is greatly facilitated by the presence of the G alpha subunit, which has also been shown to participate in an adaptation to pheromone. PMID- 1900040 TI - A naturally occurring truncated form of FosB that inhibits Fos/Jun transcriptional activity. AB - Fos and Jun transcription factors are induced by a variety of extracellular signaling agents. We describe here an unusual member of the Fos family that is also induced, namely, a truncated form of FosB (delta FosB) missing the C terminal 101 amino acids of FosB. delta FosB retains the dimerization and DNA binding activities of FosB but has lost the ability in transfection assays to activate a promoter with an AP-1 site and to repress the c-fos promoter. Rather, delta FosB inhibits gene activation by Jun or Jun + Fos and inhibits repression of the c-fos promoter by FosB or c-Fos, presumably by competing with full-length Fos proteins at the steps of dimerization with Jun and binding to DNA. In stimulated cells delta FosB may act to limit the transcriptional effects of Fos and Jun proteins. PMID- 1900041 TI - Coronary artery disease and apolipoprotein A-I/C-III gene polymorphism: a study of Saudi Arabians. AB - The infrequent band of 3.2-kb of the apolipoprotein A-I/C-III polymorphic region has previously been found to be associated with coronary artery disease and with hypertriglyceridaemia in Caucasians. We studied the apolipoprotein A-I/C-III gene cluster polymorphism in 97 Saudi Arabians in relation to coronary artery disease. Patients were categorized as being with or without coronary artery disease on the basis of coronary angiography. Genomic blotting of Sac I-digested chromosomal DNA with the use of an apolipoprotein A-I gene probe revealed 4.2-kb and 3.2-kb hybridization bands. The genotype frequency of patients with and without coronary artery disease was not different. The frequency of the 3.2-kb allele occurred in 16% of patients with coronary artery disease and in 21% of patients with normal coronary arteries (non-significant). In conclusion, we have not been able to confirm in Saudi Arabians associations previously reported in Caucasians of the 3.2-kb band and coronary artery disease. PMID- 1900042 TI - Alveolar epithelial cells express both plasminogen activator and tissue factor. Potential role in repair of lung injury. PMID- 1900043 TI - Modulation of cellular repair response patterns. PMID- 1900044 TI - Transforming growth factor-beta production by dog mastocytoma cells. Storage and release from mast cell granules. PMID- 1900046 TI - [Neurofibromatosis]. PMID- 1900045 TI - [Endoscopy, shockwave lithotripsy and local lysis in complicated pigmentary calculi of extra- and intrahepatic bile ducts]. AB - Endoscopy, extracorporeal shockwave lithotripsy (ESWL) and local lysis with alkaline solution of EDTA and bile salts in water were applied in combination in four patients with extra- and intrahepatic pigment stones as well as calcium bilirubinate covered concrements of the biliary tract. In the first patient (a man aged 80 years) a giant concrement of the bile duct was broken up after ESWL by three weeks of local chemical lysis and the fragments were removed by endoscopy. In the second case (man, aged 72), a nonextractable pigment stone was at first reduced in size by four-day local lysis and then removed endoscopically. Intrahepatic pigment stones were completely removed in the other two patients (boy of 12, man of 62) by local lysis only in 3 and 15 weeks, respectively. Even long-term use of the alkaline solution may not cause any serious side effects. Breaking up of stones after size reduction with ESWL of giant stones, size reduction of intact stones and contact lysis of intrahepatic stones are three important indications for chemical dissolution of biliary tract stones, respectively. PMID- 1900047 TI - [Diagnosis of tuberculosis]. PMID- 1900048 TI - Gene for the ADP-ribosylatable elongation factor 2 from the extreme thermoacidophilic archaebacterium Sulfolobus acidocaldarius. Cloning, sequencing, comparative analysis. AB - The gene coding for ADP-ribosylatable elongation factor 2 (EF-2) from the extreme thermoacidophilic archaebacterium Sulfolobus acidocaldarius has been cloned and its sequence is reported. Amino acid sequence comparisons showed that EF-2 from S. acidocaldarius is more closely related to eukaryotic EF-2 than to eubacterial EF-G. Consensus sequences are derived from comparison of a region around the unique amino acid diphthamide, which is the target for ADP-ribosylation by diphtheria toxin in archaebacteria and eukaryotes. The conserved positions are likely to constitute a recognition site for the toxin and the histidine-modifying enzymes. A single transcript of approximately the size of the EF-2 gene was observed in Northern blot experiments. Transcription initiation and termination signals were identified in the immediate vicinity of the respective translation start and stop codons of the gene. These results indicate that, in contrast to all prokaryotic EF-2 genes studied previously, the gene of S. acidocaldarius is not located within the streptomycin operon but is transcribed separately. PMID- 1900049 TI - An unusual class I (Schiff base) fructose-1,6-bisphosphate aldolase from the halophilic archaebacterium Haloarcula vallismortis. AB - An electrophoretically homogeneous class I (Schiff base) alsolase has been isolated for the first time from the archaebacterial halophile Haloarcula (Halobacterium) vallismortis. The aldolase was characterized with respect to its molecular mass, amino acid composition, salt dependency, immunological cross reactivity and kinetic properties. The subunit mass of aldolase is 27 kDa, which is much smaller than other class I aldolases. By the gel filtration method, the molecular mass of the halobacterial enzyme was estimated as 280 +/- 10 kDa, suggesting a decameric nature. In contrast to many halobacterial proteins, the H. vallismortis aldolase, though a halophilic enzyme, did not show an excess of acidic residues. Unlike the eukaryotic aldolases, the activity of the halobacterial enzyme was not affected by carboxypeptidase digestion. The general catalytic features of the enzyme were similar to its counterparts from other sources. No antigenic similarity could be detected between the H. vallismortis aldolase and class I aldolase from eubacteria and eukaryotes or class II halobacterial aldolases. PMID- 1900050 TI - Fine tuning of the catalytic properties of human carbonic anhydrase II. Effects of varying active-site residue 200. AB - The active-site residue Thr200 in human carbonic anhydrase II has been replaced by several different amino acids by site-directed mutagenesis. The CO2 hydration and 4-nitrophenyl acetate hydrolase activities of these variants have been measured, as well as inhibition by the monovalent anion, SCN-. The results show that the replacement of Thr200 with Ser or Ala has no significant effect on the catalyzed rates of CO2 hydration. Also, variants with Asn200 and Gly200 have high activities, whereas the activities of variants with Val, Ile or Arg at position 200 are reduced by factors of 2-3 compared to the unmodified enzyme. The variant with Asp200 has a very low activity in both reactions studied, while most of the other variants have enhanced esterase activities, Thr200----Arg isoenzyme II as much as sevenfold. The Asp200 variant has a low affinity for SCN- as well as for a sulfonamide inhibitor, whereas all the other variants bind SCN- more strongly than unmodified enzyme. While His200 characterizes carbonic anhydrases I, the presence of Arg, Val or Ile as well as His at position 200 in human isoenzyme II seems to result in isoenzyme-I-like functional properties. PMID- 1900051 TI - Multiple alpha-tubulin isoforms in cilia and cytoskeleton of Tetrahymena pyriformis generated by post-translational modifications. Studies during reciliation. AB - alpha-Tubulin microheterogeneity was studied in Tetrahymena pyriformis. Using two dimensional electrophoretic analysis, we found between five and seven alpha tubulin and four beta-tubulin isoforms in cilia and four or five alpha-tubulins and two beta-tubulins in cytoskeleton. Immunoblotting assay with anti-(acetyl alpha-tubulin) monoclonal antibody 6-11B-1 and [3H]acetate labelling revealed that the alpha-tubulin isoforms are post-translationally modified by acetylation. Our results also show that tubulins in the soluble cytoplasmic fraction are not acetylated. Nevertheless, a slight reaction with the antibody 6-11 B-1 can be observed in the taxol and vinblastine-treated cytoplasmic pool. Pulse/chase experiments using [35S]methionine during cell reciliation have demonstrated that the basic alpha-tubulin isoforms are converted into acidic isoforms in the absence of protein synthesis, suggesting that the basic alpha-tubulin is the precursor of the acidic forms which are found in cilia and cytoskeleton. In-vivo translation selection demonstrated the existence of a single precursor molecule which corresponded to the most basic alpha-tubulin. Taken together, our results provide evidence for the existence of post-translational modifications, namely acetylation. Nevertheless, other post-translational mechanisms involved in the biosynthesis of microtubules of cilia and cytoskeleton are required to explain the whole alpha-tubulin heterogeneity. PMID- 1900052 TI - Tissue-specific and time-coordinated hormone regulation of plasminogen-activator inhibitor type I and tissue-type plasminogen activator in the rat ovary during gonadotropin-induced ovulation. AB - The plasminogen-activator system provides proteolytic activity in many biological processes. The regulation of plasminogen activation may occur at many levels including the synthesis and secretion of plasminogen activators (PA) and the specific inhibition of PA activity by inhibitors. PA-inhibitor type-1 (PAI-1) is an efficient inhibitor of tissue-type PA (tPA) and urokinase-type PA (uPA) that may therefore be instrumental for the control of plasminogen activation. To investigate if coordinated regulation of PA and PA inhibitors take place in vivo in response to physiological signals, we have examined the regulation of PAI-1 and tPA in the ovary during gonadotropin-induced ovulation. We found that PAI-1, as well as tPA activity and mRNA levels, were coordinately regulated by gonadotropins in a time-dependent and cell-specific manner, such that a surge of PA-activity was obtained just prior to ovulation. Both theca-interstitial and granulosa cells synthesized PAI-1, but their maximal PAI-1 expression occurred at different times during the periovulatory period, ensuring inhibition of proteolytic activity in ovarian extra cellular compartments both before and after ovulation. The coordinated regulation of tPA and PAI-1 in the ovary may fine-tune the peak of PA activity which may be important for the regulation of the ovulatory process. PMID- 1900053 TI - Determining a fair price for inpatient psychiatric care. PMID- 1900054 TI - Binding of the specific ligand to Fc receptors on Trypanosoma cruzi increases the infective capacity of the parasite. AB - The infective capacity of Trypanosoma cruzi was significantly increased after treatment with monoclonal IgG1 antibodies, whether or not specific for the parasite; minimal or no change in infectivity was seen after treatment with IgG2a, IgG2b or IgG3 monoclonal antibodies. The stimulatory effect was evidenced by elevated numbers of trypanosomes invading mammalian host cells in vitro compared to parasites treated with medium alone. Greater infectivity was also induced by pure human Fc, suggesting a role for Fc receptors on the organism. This inference received support in the fact that protein A inhibited the stimulatory effect of Fc. In addition, Fc-treated parasites incubated with fluorescein-labelled F(ab')2 from goat anti-human IgG exhibited fluorescence detectable by both ultraviolet microscopy and flow cytometry. 125I-Fc binding to T. cruzi was found to be saturable at 0 degrees and was inhibited by cold Fc but not by bovine serum albumin (BSA) or orosomucoid. Interestingly, 125I-Fc binding was greater at 37 degrees and it was not saturable with the concentrations that did saturate at 0 degrees. Possibly, Fc might up-regulate expression of its own receptor and greater endocytosis could take place at 37 degrees. Significant increases in infectivity were detectable after a 40 min pretreatment with Fc- hinting that Fc could trigger a chain of biochemical events underlying the phenomenon--and were reversible, becoming undetectable 2 hr after Fc removal. The average number of Fc receptors per parasite, determined at 0 degrees (at which binding saturation was possible), was estimated as 5 x 10(5), the dissociation constant was of the order of 10(-6)-10(7)M. The present results define an important biological role for an Fc-binding T. cruzi surface component and expose the capacity of this organism to exploit even elements of the immune system in its quest to attain intracellular localization, required for multiplication. PMID- 1900055 TI - Preferential expression of IL-2 receptor subunits on memory populations within CD4+ and CD8+ T cells. AB - Using anti-Tac and anti-Mik-beta 1 monoclonal antibodies to alpha and beta subunits of the interleukin-2 receptor (IL-2R), respectively, a marked difference in expression of IL-2R subunits on blood CD4+ and CD8+ T cells was demonstrated between adults and newborns. In the adult blood, reciprocal expression of IL-2R alpha and IL-2R beta was observed in CD4+ and CD8+ T cells. Some CD4+ T cells expressing IL-2R alpha were often detected, but IL-2R beta + CD4+ cells were very few. On the other hand, CD8+ T cells expressed significant IL-2R beta but little IL-2R alpha. In marked contrast to adult individuals, both CD4+ and CD8+ T cells from the newborns, which seemed to consist mainly of naive populations, showed only negligible expression of IL-2R subunits. It was found that IL-2R subunits appeared to be preferentially expressed on CD4+ and CD8+ T cells with memory phenotypes in the adult blood. Isolated memory (CD45RO+) CD4+ and CD8+ T cells, unlike naive (CD45RO-) ones, were able to proliferate in response to exogenous IL 2 as well as the recall antigen. The present results suggest that IL-2R subunits expressed on circulating T-cell subsets may play an important role in memory T cell function. PMID- 1900056 TI - Murine T lymphocytes and T-lymphoma cells produce chondroitin sulphate and heparan sulphate proteoglycans and free heparan sulphate glycosaminoglycan. AB - Normal murine splenic T lymphocytes and T-lymphoma cells were incubated with [35S]sulphate in low-sulphate medium for 4 hr. Gel filtration and SDS-PAGE revealed that the radiolabelled macromolecules secreted by these cells were almost exclusively chondroitin sulphate and heparan sulphate proteoglycans of relatively low molecular weight (MW), 100,000-200,000. Triton X-100 extracts of the cells contained similar proteoglycans. Under the conditions employed the incorporation of radiolabel by cells grown in vivo was equally distributed between cell-retained and secreted fractions, whereas cells grown in vitro retained some 75% of incorporated label. In general heparan sulphate predominated over chondroitin sulphate in both secreted and cell-retained fractions. Cell extracts also contained a minor proportion of free glycosaminoglycan, which is almost exclusively heparan sulphate. These chains, like those incorporated into the proteoglycan, were around 12,000 MW. The T-lymphoma cells RDM-4, whether grown in vitro or in vivo, also incorporated a substantial proportion of [35S]sulphate into a single, cell-retained protein, 100,000 MW. No such radiolabelled protein was detectable in T cells. PMID- 1900057 TI - Mycobacteria and human autoimmune disease: direct evidence of cross-reactivity between human lactoferrin and the 65-kilodalton protein of tubercle and leprosy bacilli. AB - We document here by Western immunoblotting and immunogold ultracytochemistry that polyclonal antibodies against human lactoferrin (Lf) bind to tubercle and leprosy bacilli. In situ immunogold labeling of Mycobacterium leprae (present in armadillo liver and in human skin) and of Mycobacterium tuberculosis indicated that receptors for anti-Lf antibodies were present both on the cytoplasm and on the envelope of the bacilli. We found by immunoblotting that the 65-kDa heat shock protein is the major component of M. leprae and M. tuberculosis that is responsible for the binding of the anti-Lf probe. Furthermore, we show that anti Lf immunoglobulin G eluted from the nitrocellulose-transferred mycobacterial 65 kDa protein band did bind back to Lf. Ultracytochemistry of biopsy samples of human lepromas showed that dead or severely damaged M. leprae was strongly marked by the anti-Lf antibodies; a similar pattern of immunogold marking was observed on M. leprae when antibodies against the 65-kDa mycobacterial protein were used. Our results offer direct evidence that the 65-kDa protein of leprosy and tubercle bacilli is recognized with specificity by antibodies against the human protein Lf. The Lf-65-kDa protein antigenic cross-reactivity may contribute to the formation of autoantibodies and immune complexes as well as to other autoimmune events that are frequent in tuberculosis and leprosy. Our immunocytochemical data also suggest that the cross-reactivity may persist for some time after the death of mycobacteria in infected hosts. PMID- 1900058 TI - Mechanism of action of Moraxella bovis hemolysin. AB - Bovine erythrocytes (RBCs) exposed to Moraxella bovis culture supernatants exhibited rapid leakage of intracellular K+ (95% in 10 min), slower cell swelling (1.20-fold increase in mean corpuscular volume in 20 min), and subsequent lysis (76% leakage of hemoglobin in 25 min). Incubation media made hypertonic by the addition of 75 mM carbohydrates with molecular diameters of 0.72 to 1.32 nm prevented hemolysin-induced RBC swelling, but incubation media made hypertonic by the addition of carbohydrates with molecular diameters of less than 0.72 nm did not protect against hemolysin-induced RBC swelling. Raffinose (75 mM; molecular diameter, 1.14 nm) did not block hemolysin-induced K+ leakage but did block hemolysis. These findings support the hypothesis that hemolysin-induced lysis occurs by colloid-osmotic swelling and are compatible with M. bovis hemolysin acting as a pore-forming cytolysin. Assuming that M. bovis hemolysin acts as a transmembrane molecular sieve, then the functional size of the hemolysin transmembrane pores in bovine RBCs is approximately 0.9 nm, the molecular size of sucrose. Hemolytic activity was inhibited by the Ca2+ chelator ethylene glycol bis (beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA), but hemolysin induced K+ leakage was not affected by EGTA. PMID- 1900059 TI - Protection against experimental pseudomembranous colitis in gnotobiotic mice by use of monoclonal antibodies against Clostridium difficile toxin A. AB - The pathogenicity of Clostridium difficile is due to the production of two toxins (toxins A and B). We prepared monoclonal antibodies against toxin A and determined whether axenic mice passively immunized with the monoclonal antibodies were protected against C. difficile disease. The mice were kept in an isolator and were given ascites fluid intravenously prior to challenge with a toxinogenic strain of C. difficile. Control mice and mice receiving ascites fluid devoid of toxin antibody died within 2 days and had high levels of toxins A and B in their feces. Mice that received ascites fluid containing high amounts of toxin A monoclonal antibodies directed against the repeating units of the toxin survived. In protected mice, toxin B levels were similar to those in dying mice, but toxin A levels were greatly reduced. These data show that passive immunity induced by monoclonal antibodies against toxin A was effective against pseudomembranous cecitis. PMID- 1900060 TI - Localization of major histocompatibility complex class II molecules in phagolysosomes of murine macrophages infected with Leishmania amazonensis. AB - Leishmania-infected macrophages are potential antigen-presenting cells for CD4+ T lymphocytes, which recognize parasite antigens bound to major histocompatibility complex class II molecules (Ia). However, the intracellular sites where Ia and antigens may interact are far from clear, since parasites grow within the modified lysosomal compartment of the host cell, whereas Ia molecules seem to be targeted to endosomes. To address this question, the expression and fate of Ia molecules were studied by immunocytochemistry in Leishmania amazonensis-infected murine macrophages stimulated with gamma interferon. In uninfected macrophages, Ia molecules were localized on the plasma membrane and in perinuclear vesicles, but they underwent a dramatic redistribution after infection, since most of the intracellular staining was then associated with the periphery of the parasitophorous vacuoles (p.v.) and quite often polarized towards amastigote binding sites. The Ii invariant chain, which is transiently associated with Ia during their intracellular transport, although well expressed in infected macrophages, apparently did not reach the p.v. Similar findings were observed with macrophages from mice either resistant or highly susceptible to Leishmania infection. In order to determine the origin of p.v.-associated Ia, the fate of plasma membrane, endosomal, and lysosomal markers, detected with specific antibodies, was determined after infection. At 48 h after infection, p.v. was found to exhibit a membrane composition typical of mature lysosomes. Overall, these data suggest that (i) Ia located in p.v. originate from secondary lysosomes involved in the biogenesis of this compartment or circulate in several endocytic organelles, including lysosomes and (ii) p.v. could play a role in antigen processing and presentation. Alternatively, the presence of high amounts of Ia in p.v. could be due to a Leishmania-induced mechanism by means of which this organism may evade the immune response. PMID- 1900062 TI - Phosphate-containing proteins and glycoproteins of the cell wall of Candida albicans. AB - The distribution of phosphate, carbohydrate, and protein in the cell wall components extracted from intact yeast cells of Candida albicans by beta mercaptoethanol (beta ME) at pH 8.6 was examined by analysis of the material separated by DEAE-cellulose chromatography. All protein peaks did not coincide with peaks of both carbohydrate and phosphate. Subsequent analysis was performed on material obtained from yeast cells and germ tubes which were grown in medium containing [32P]phosphate. Two extracts were obtained by treating cells with beta ME or with zymolyase following beta ME. The extracts were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, followed by autoradiography. beta ME-extracted material contained high-molecular-mass (HMM), greater than or equal to 200 kDa, polydisperse material and a major and minor band of 19 to 20 kDa, Zymolyase extracts contained (i) three components of less than or equal to 40 kDa, one of which may correspond to the major beta ME band; (ii) four bands within the HMM region which may correspond to previously reported bands; and (iii) one band of 100 to 120 kDa. After longer exposures, additional midrange bands were detected in the zymolyase extract. In extracts treated with endo-beta N-acetylglucosaminidase H, the HMM polydisperse material increased in mobility although retaining sufficient radiolabel for detection. Western immunoblot analysis of extracts with germ tube-specific antiserum and a germ tube-specific monoclonal antibody and concanavalin A showed that not all components contained detectable phosphate, not all glycoproteins contained detectable phosphate, and at least one 19- to 20-kDa protein may be phosphorylated in the absence of carbohydrate. PMID- 1900061 TI - Purification and characterization of major antigens from a Mycobacterium bovis culture filtrate. AB - Ten major antigens from Mycobacterium bovis culture filtrate of 39, 32, 30, 25, 24, 22 (a and b forms), 19, 15, and 12 kDa have been purified and characterized by classical physicochemical methods. With monoclonal antibodies and/or N terminal amino acid sequencing data, it was found that the antigens of 32, 30, 24, 22 (a), 19, and 12 kDa are related to M. bovis or M. tuberculosis antigens P32, MPB59, MPB64, MPB70, 19 kDa, and 12 kDa, respectively. The 39-, 25-, 22 (b) , and 19-kDa antigens showed concanavalin A-binding properties and were positive in a glycan detection test, suggesting that they are glycoproteins. The 25- and 22 (b)-kDa proteins were found to be glycosylated forms of MPB70. PMID- 1900063 TI - Preparation, characterization, and immunogenicity of meningococcal immunotype L2 and L3,7,9 phosphoethanolamine group-containing oligosaccharide-protein conjugates. AB - A method was developed for the well-defined coupling of phosphoethanolamine group (PEA)- and carboxylic acid group-containing polysaccharides and oligosaccharides to proteins without the need for extensive modification of the carbohydrate antigens. The carboxylic acid group of the terminal 2-keto-3-deoxyoctulosonic acid moiety was utilized to introduce a thiol function in meningococcal immunotype L2 and L3,7,9 lipopolysaccharide-derived oligosaccharides. The thiol group-containing oligosaccharides were subsequently coupled to bromoacetylated proteins. Immunotype L2 and L3,7,9 PEA group-containing oligosaccharide-tetanus toxoid conjugates were prepared, and their immunogenicities were studied in rabbits. Both the immunotype L2 and immunotype L3,7,9 conjugates evoked high immunoglobulin G (IgG) antibody titers after the first booster injection. These conjugates also displayed an ability to induce long-lasting IgG antibody levels which could be detected until 9 months after one booster injection at week 3. The adjuvant Quil A enhanced the immune response to all the conjugates to a minor extent, which is in contrast with reported adjuvant effects of Quil A on these types of antigens in mice. A conjugate prepared from the dephosphorylated L3,7,9 oligosaccharides evoked a significantly lower IgG response than a similar PEA containing conjugate, and enzyme-linked immunosorbent assay inhibition studies indicated a different epitope specificity. Furthermore, antisera elicited with the complete bacteria contained antibodies directed against PEA-containing epitopes, which stresses the importance of the presence of unmodified PEA groups in meningococcal lipopolysaccharide-derived oligosaccharide-protein conjugates. The procedure developed offers an elegant solution for the specific coupling of meningococcal PEA-containing oligosaccharides to proteins and may therefore be a very useful tool in the development of a vaccine against group B meningococci. PMID- 1900064 TI - Resistance to acute Trypanosoma cruzi infection resulting from immunization of mice with a 90-kilodalton antigen from metacyclic trypomastigotes. AB - The stage-specific 90-kDa surface antigen of Trypanosoma cruzi metacyclic trypomastigotes was affinity purified and used for immunization studies. Mice immunized with the 90-kDa antigen plus alum as an adjuvant were resistant to challenge with Tulahuen strain metacyclic forms, displaying either reduced or subpatent parasitemias. Mice immunized with the purified antigen without adjuvant or with antigen plus Freund adjuvant or glucan developed high parasitemias, comparable to those of nonimmunized controls, upon metacyclic challenge. Sera of mice immunized with the 90-kDa antigen plus alum showed complement-dependent trypanolytic activity and also greatly inhibited the invasion of Vero cells by metacyclic forms of G and Tulahuen strains in vitro. These sera were found by a competition binding assay to contain antibodies that recognized the same or topographically related sites as the monoclonal antibody 1G7, an antibody previously shown to reduce the infectivity of metacyclic forms in vivo and in vitro. In contrast, 1G7-related antibodies were poorly represented in sera with negative or low trypanolytic activity, such as those from mice immunized with purified antigen without adjuvant. PMID- 1900065 TI - Differential adherence of hydrophobic and hydrophilic Candida albicans yeast cells to mouse tissues. AB - Using an ex vivo binding assay, we previously demonstrated that yeast cells grown at 37 degrees C display binding specificity in mouse spleen, lymph node, and kidney tissues. In spleen and lymph node tissues, binding was predominantly in regions rich in macrophages. Here, we tested the possibility that hydrophobic and hydrophilic cells bind differentially to host tissues. Hydrophobic and hydrophilic yeast cells of four Candida albicans strains were incubated for 15 min at 4 degrees C with cryostat sections of organs that had been rapidly frozen after removal from BALB/cByJ mice. Unattached cells were removed by washing, and the sections were examined. Hydrophobic cells bound diffusely and abundantly to all tissues, while hydrophilic cell attachment was restricted to specific sites. For example, hydrophobic cells bound to the white and red pulp and the marginal zones in spleens, whereas hydrophilic cells attached primarily to the marginal zones. Hydrophobic yeast cells attached throughout lymph node tissue including paracortical areas, but hydrophilic cell attachment occurred primarily at the subcapsular and trabecular sinuses, EDTA inhibited the adherence of hydrophilic cells but not hydrophobic cells to mouse tissues. Hydrophobic C. albicans strains displaying similar levels of hydrophobicity differed quantitatively in their levels of attachment to kidney and spleen tissues, confirming our earlier observation that surface hydrophobicity is not the sole determinant in adherence to host cells. Other studies have shown that hydrophobic and hydrophilic cells display different virulence characteristics related to their surface properties and that hydrophobic cells are more virulent than hydrophilic cells. Taken together, the present results suggest that the enhanced virulence of hydrophobic cells over hydrophilic cells may be due, in part, to the potential of hydrophobic cells to bind throughout various organs following clearance from the bloodstream. PMID- 1900067 TI - Cerebral blood flow with the indicator fractionation of [14C]iodoantipyrine: effect of PaCO2 on cerebral venous appearance time. AB - The indicator fractionation technique using a diffusible indicator as a tracer for the determination of CBF has been used for numerous investigations of the cerebral circulation and its pathophysiology. The diffusible tracer is "trapped" in the brain based on the proper delay between tracer injection and cessation of the cerebral circulation by decapitation before the appearance of the tracer in the cerebral venous circulation. If this delay is too long, the quantitative assumption of the indicator fractionation technique will not be met, and CBF values will be underestimated. In 13 Sprague-Dawley rats anesthetized with pentobarbital, the appearance of [14C]iodoantipyrine at the torcular was assessed as a function of PaCO2. An inverse linear relationship between PaCO2 (in millimeters of mercury) and cerebral venous appearance, Ta (in seconds), was established with the regression equation Ta = -0.0842.PaCO2 + 12.3 (R2 = 0.70, slope significantly different from zero, p less than 0.001). Ta varied between 5 and 12 s and PaCO2 varied between 84 and 18 mm Hg, respectively. Thus, in low flow states, the decapitation time may be lengthened to 12 s, whereas in high flow states, the time must be 5 s to eliminate the possibility of backflux of tracer out of the brain. PMID- 1900066 TI - Splenic and granuloma T-lymphocyte responses to fractionated soluble egg antigens of Schistosoma mansoni-infected mice. AB - Soluble egg antigens (SEA) secreted by the eggs of Schistosoma mansoni worms induce a T-cell-mediated granulomatous response that is principally responsible for the pathology of the disease. In the present study sodium dodecyl sulfate polyacrylamide gel electrophoresis-separated SEA proteins were divided into nine fractions (less than 21, 25 to 30, 32 to 38, 40 to 46, 50 to 56, 60 to 66, 70 to 90, 93 to 125, and greater than 200 kDa), electroeluted, and utilized in in vitro lymphoproliferation assays. T-cell-enriched spleen cells from acutely infected mice responded to all nine fractions, while those from chronically infected mice responded to only the 50- to 56- and the 60- to 66-kDa fractions. Depletion of the CD4+ T-cell subset among acute and chronic-infection spleen cells abrogated the response. Depletion of the CD8+ T-cell population resulted in increased proliferation in response to fractions by acute-infection T cells and facilitated responsiveness to hitherto-inactive SEA fractions in chronic-infection T cells. Acute-infection CD4+ granuloma T cells responded to the 40- to 46-, 50- to 56-, 70- to 90-, 93- to 125-, and greater than 200-kDa fractions, while the chronic infection granuloma T cells responded only to the greater than 200-kDa fraction of SEA. Selective depletion of the CD4+ T-cell subset when acute-infection granuloma lymphocytes were tested abrogated proliferation, whereas subset depletions when chronic-infection granuloma cells were tested indicated that both CD4+ and CD8+ T cells respond to the greater than 200-kDa fraction. The present study reveals differences between acute- and chronic-infection splenic and granuloma T cells in the pattern of T-cell blastogenic responses to fractionated SEA. PMID- 1900068 TI - Immunoreactive inhibin concentrations in adult men: presence of a circadian rhythm. AB - The circadian and chronological changes in inhibin secretion were studied in normal adult men. To determine the diurnal release of inhibin, blood samples were collected every hour for 24 h from five healthy young adult men, and serum inhibin was measured by RIA. During the evening and the night, serum inhibin concentrations were relatively low; the lowest value was observed at 2200 h. At 0700 h, inhibin started to increase, reached a peak at 0900 h, and then gradually decreased. These results suggest that inhibin secretion is circadian. Testosterone and cortisol also showed circadian rhythms. In some of the five volunteers, the serum concentrations of inhibin, testosterone, and cortisol were superimposable, but no significant relationship was observed between the serum inhibin and FSH concentrations. With regard to the age-related changes in basal inhibin levels, the highest values were observed in the twenties, and lower values were found with aging. This relationship suggests that increased FSH in elderly men might be due to the reduced amount of peripheral inhibin. PMID- 1900069 TI - Serum gonadotropin, sex steroid, and immunoreactive inhibin levels in the first two years of life. AB - To characterize the changes in serum immunoreactive inhibin (INH) in the first 2 yr of life, blood samples were obtained from 46 boys (age range, 61-659 days) and 37 girls (76-666 days) undergoing minor surgery for nonendocrine related conditions. Serum levels were compared with those of simultaneously measured FSH, LH, and either testosterone (T) or estradiol (E2). In the boys, the levels of all 4 hormones fell progressively with age up to about 300 days, with a minor fall only in the second year. FSH (0.7-1.4 IU/L) was initially at the lower adult male limit, while LH (3.2-5.0 IU/L) was at the midrange. T levels (2.2-3.3 nmol/L) were in the adult female range, while INH (200-820 U/L) was in the midrange for men. In the youngest girls, FSH levels (12-26 IU/L) were frequently above the upper limit of normal for the adult follicular phase, but fell to approximately 2.0 IU/L after 300 days. LH levels (0.5-3.5 IU/L) were at the lower adult normal limit and changed little with age, while E2 levels in the youngest girls (280-550 pmol/L) were in the midfollicular range, but were generally less than 10 pM at more than 200 days. INH levels (175-260 U/L) were in the low adult range initially, but the majority were undetectable over 200 days. In the boys, significant negative correlations were observed for all 4 hormones with age, while FSH, LH, and T were positively correlated with INH. In the girls, there were weaker negative correlations of the 4 hormones with age, but no significant correlations between the gonadotropins and INH. E2 was strongly correlated with INH. Thus, the previously described early postnatal activation of the hypothalamo pituitary-gonadal axis involves INH as well as the se steroids and gonadotropins. FSH levels in young girls were strikingly high, and INH levels were much higher in boys than girls. The low INH levels in girls may contribute to the elevated FSH seen during the period of neonatal gonadal activation. PMID- 1900070 TI - Screening for lupus anticoagulant and anticardiolipin antibodies in women with fetal loss. AB - Sixty six women with first or second trimester fetal loss were investigated for the presence of lupus anticoagulant by routine coagulation tests and the dilute Russell's viper venom time with a platelet neutralisation procedure, and for raised anticardiolipin antibodies by an enzyme linked immunosorbent assay. Of 35 women with recurrent fetal loss, seven were positive for lupus anticoagulant and six had increased IgG anticardiolipin antibodies, while of 31 women with only one or two episodes of fetal loss, one had lupus anticoagulant and none increased IgG anticardiolipin antibodies. These findings were significantly different. There was no difference in the incidence of increased IgM anticardiolipin antibodies between the two groups (three and two cases, respectively). A further 11 women with intrauterine death in the third trimester were studied and lupus anticoagulant and raised IgM anticardiolipin antibodies were found in one case. No woman was known to have systemic lupus erythematosus. It is concluded that lupus anticoagulant and increased IgG anticardiolipin antibodies are independently associated with recurrent first and second trimester fetal loss and that such cases should be investigated, even in the presence of otherwise good health, by a comprehensive methodological approach. PMID- 1900071 TI - Evaluation of Clinitek 200 and Rapimat II/T for screening for urinary tract infection. AB - Two machines, the Clinitek 200 and the Rapimat II/T, were evaluated for their ability to screen urine samples for significant bacteriuria and other elements indicative of urinary tract pathology. The automated screening procedures were compared with a conventional approach of microscopy and quantitative culture for 1020 urine specimens obtained from patients in a 700 bed general hospital. When compared with the bacterial culture method both machines gave identical results with a negative predictive value of 0.99, while when compared with microscopy alone the Clinitek 200 and Rapimat II/T gave negative predictive values of 0.92 and 0.87, respectively. It is concluded that both machines would provide cost effective screening of urine specimens. PMID- 1900072 TI - Treating insulin resistance in hypertension with metformin reduces both blood pressure and metabolic risk factors. AB - Insulin resistance and hyperinsulinaemia may play an important role in both the development of hypertension and its accompanying metabolic aberrations. In order to investigate this possibility, nine non-obese, non-diabetic, non-smoking, middle-aged men with untreated hypertension were treated with metformin 850 mg b.i.d. for 6 weeks as a pilot study and within-patient comparison. Metformin decreased total and LDL-cholesterol (P less than 0.01), triglyceride (P less than 0.01), fasting plasma insulin (P less than 0.01) and C-peptide levels (P less than 0.02). Glucose disposal, an indicator of insulin action measured by means of the euglycaemic clamp technique, increased (P less than 0.001). Tissue plasminogen activator (t-PA) activity increased (P less than 0.02), and t-PA antigen decreased (P less than 0.01), whereas plasminogen activator inhibitor (PAI-1) and fibrinogen were unaffected by metformin treatment. Body weight remained unchanged. Withdrawal of metformin was associated with the return of both blood pressure and metabolism towards the initial levels. In conclusion, metformin treatment increased insulin action, lowered blood pressure, improved the metabolic risk factor profile and tended to increase the fibrinolytic activity in these mildly hypertensive subjects. These results support the view that insulin resistance plays a role in hypertension, and may open up a new field for the alleviation of abnormalities associated with cardiovascular disease. PMID- 1900073 TI - Cytokines kill malaria parasites during infection crisis: extracellular complementary factors are essential. AB - Malaria infection crisis, at which the parasitemia drops precipitously and the parasite loses infectivity to the mosquito vector, occurs in many natural malaria systems, and has not been explained. We demonstrate that in a simian malaria parasite (Plasmodium cynomolgi in its natural host, the toque monkey), the loss of infectivity during crisis is due to the death of circulating intraerythrocytic gametocytes mediated by crisis serum. These parasite-killing effects in crisis serum are due to the presence in the serum of cytokines tumor necrosis factor and interferon gamma, which are produced by the host as a result of the malaria infection. The killing activity of each cytokine is absolutely dependent upon the presence of additional, as yet unidentified factor(s) in the crisis serum. PMID- 1900074 TI - Requirement of dendritic cells and B cells in the clonal deletion of Mls-reactive T cells in the thymus. AB - The present study was performed to identify cells responsible for the elimination of T cells reactive with minor lymphocyte-stimulating (Mls) antigens during T cell development. Experiments were carried out in a fetal thymus organ culture (FTOC) system. To examine the tolerance-inducing activity, various populations of cells from adult CBA/J (Mls-1a) mice were injected into deoxyguanosine (dGuo) treated FTOC of C3H/He (Mls-1b) mice with a microinjector, and 2 d later, the thymus lobes were injected with fetal thymus cells from C3H/He mice as T cell precursors. After 14 d of cultivation, cells were harvested and assayed for the expression of the T cell receptor V beta 6 element. The absence or marked reduction of T cells expressing V beta 6 at high levels (V beta 6high) was regarded as indicating the deletion of Mls-1a-reactive T cells. T cell-depleted populations of thymic as well as splenic cells from CBA/J mice were able to induce clonal deletion. Further characterization of the effector cells was carried out by fractionating the spleen cells before injecting them into dGuo FTOC. None of the dish-adherent population, dish-nonadherent population, or purified B cells alone were able to induce clonal deletion, whereas the addition of purified B cells to adherent cells restored tolerance inducibility. It was further shown that a combination of CBA/J B cells and C3H/He dendritic cells was effective in eliminating Mls-reactive clones. These results indicate that for the deletion of clones reactive with Mls antigens during T cell development in the thymus, both DC and B cells are required. PMID- 1900075 TI - Distinct mechanisms of neonatal tolerance induced by dendritic cells and thymic B cells. AB - To assess the role of different types of antigen-presenting cells (APC) in the induction of tolerance, we isolated B cells, macrophages, and dendritic cells from thymus and spleen, and injected these into neonatal BALB/c mice across an Mls-1 antigenic barrier. One week after injection of APC from Mls-1-incompatible mice or from control syngeneic mice, we measured the number of thymic, Mls-1a reactive, V beta 6+ T cells and the capacity of thymocytes to induce a graft-vs. host (GVH) reaction in popliteal lymph nodes of Mls-1a mice. Injection of thymic but not spleen B cells deleted thymic, Mls-1a-reactive V beta 6+ T cells and induced tolerance in the GVH assay. The thymic B cells were primarily of the CD5+ type, and fluorescence-activated cell sorter-purified CD5+ thymic B cells were active. Injection of dendritic cells from spleen or thymus also induced tolerance, but the V beta 6 cells were anergized rather than deleted. Macrophages from thymus did not induce tolerance. Dendritic cells and thymic B cells were also effective in inducing tolerance even when injected into Mls-, major histocompatibility complex-incompatible, I-E- mice, but only thymic B cells depleted V beta 6-expressing T cells. Therefore, different types of bone marrow derived APC have different capacities for inducing tolerance, and the active cell types (dendritic cells and CD5+ thymic B cells) can act by distinct mechanisms. PMID- 1900076 TI - T cell receptor-mediated selection of functional rat CD8 T cells from defined immature thymocyte precursors in short-term suspension culture. AB - Recent results have indicated that positive and negative repertoire selection act on the major population of CD4,8 double-positive (DP) thymocytes that express 5 10-fold less T cell receptor (TCR) than mature T cells (i.e., they are TCRlow). Since DP cells obtained ex vivo are heterogeneous with regard to their stage within thymic selection, a homogeneous population of virgin DP cells suitable for selection studies was generated in vitro from their immediate precursors, the CD8 single-positive (SP) immature blast cells. To mimic TCR-mediated selection signals, these virgin DP cells were then cultured for another 2 d in the presence of immobilized anti-TCR monoclonal antibodies with or without interleukin 2 (IL 2). Daily monitoring of recovery and phenotype showed that without TCR stimulation, the cells remained DP and became small, TCRlow cells that were lost with a half-life of 1 d, regardless of the presence of IL-2. TCR stimulation resulted in rapid downregulation of CD4 and CD8, maintenance of a larger cell size, and induction of the CD53 antigen that marks mature and CD4,8 double negative rat thymocytes. In the absence of IL-2, viability decreased as rapidly as without TCR stimulation. Addition of IL-2 rescued TCR-stimulated virgin DP cells and prevented CD8 downregulation, so that 50-80% of input DP cells were recovered after 2 d as CD4-8+53+ cells. After release from modulation, these in vitro generated CD8 SP cells quantitatively upregulated the TCR to the TCRhigh phenotype and were readily induced to proliferate and exhibit cytotoxic T lymphocyte (CTL) activity in a polyclonal readout. Evidence is presented implicating an IL-2 receptor (IL-2R) not containing the p55 chain (i.e., most likely the p70 intermediate affinity IL-2R) in the TCR plus IL-2-driven in vitro differentiation of virgin DP cells towards the mature CD8 SP phenotype. PMID- 1900077 TI - Differential endocytosis of CD4 in lymphocytic and nonlymphocytic cells. AB - The endocytosis of the T cell differentiation antigen CD4 has been investigated in CD4-transfected HeLa cells, the promyelocytic HL-60 cell line, and in a number of leukemia- or lymphoma-derived T cell lines. CD4 internalization was followed using radioiodinated antibodies in an acid-elution endocytosis assay, or by covalently modifying cell surface proteins with biotin and analyzing CD4 distributions by immunoprecipitation; both approaches gave equivalent results. The assays demonstrated that in transfected HeLa cells and in HL-60 cells CD4 was constitutively internalized and recycled in the absence of ligand. Immunogold labeling and electron microscopy demonstrated that CD4 enters cells through coated pits. In contrast to the nonlymphocytic cells, T cell lines showed very little endocytosis of CD4. Measurements of fluid phase endocytosis and morphometric analysis of the endosome compartment indicated that the endocytic capacities of HeLa and lymphoid cells are equivalent and suggested that the low level of CD4 uptake in lymphocytic cells is due to exclusion of CD4 from coated pits. This conclusion was supported by experiments using truncated CD4 molecules, lacking the bulk of the cytoplasmic domain, which were internalized equally efficiently in both transfected lymphocytes and HeLa cells. Together, these results indicate that the cytoplasmic domain of CD4 mediates the different interactions with the endocytic apparatus in lymphoid and nonlymphoid cells. We suggest that the CD4-associated lymphocyte-specific protein tyrosine kinase p56lck may be involved in preventing CD4 endocytosis in T cells. PMID- 1900078 TI - Induced rearrangement of kappa genes in the BLIN-1 human pre-B cell line correlates with germline J-C kappa and V kappa transcription. AB - The human pre-B acute lymphoblastic leukemia cell line, BLIN-1, has been previously shown to undergo kappa light chain rearrangement in vitro, making it a valuable resource for analyzing pre-B to B cell differentiation. We have examined the recombination potential of BLIN-1 by characterizing several independently derived kappa-expressing subclones for DNA rearrangement and V kappa gene usage. Analysis of five kappa-expressing subclones (all having the same heavy chain rearrangement) demonstrated independent kappa light chain rearrangement events by DNA hybridization analysis. Northern blot analysis using probes recognizing the four different V kappa families revealed that two subclones used the most proximal V kappa (V kappa IV), one subclone used a V kappa I, and one subclone used a V kappa II. By polymerase chain reaction analyses, we detected transcripts from rearranged V-J-C kappa genes as well as transcripts from germline J-C kappa and V kappa in BLIN-1 cells induced to rearrange the kappa locus. kappa germline transcripts were also detected in normal developing B cell populations in fetal liver and bone marrow. Our collective results indicate that: (a) BLIN-1 can be induced to rearrange the kappa locus, and this correlates with the expression of germline kappa locus transcripts that may play a role in activating or targeting gene rearrangement; and (b) active rearrangement and usage of V genes representing different kappa families suggest that, like in the mouse, repertoire diversification in humans occurs in the presence of a fixed heavy chain rearrangement. PMID- 1900079 TI - Interferon gamma and tumor necrosis factor have a role in tumor regressions mediated by murine CD8+ tumor-infiltrating lymphocytes. AB - We have investigated the mechanisms whereby adoptively transferred murine CD8+ lymphocytes mediate tumor regressions. Noncytolytic, CD8+ tumor-infiltrating lymphocytes (TIL) eradicated established lung tumors in irradiated mice. Many cytolytic and noncytolytic CD8+ TIL cultures specifically secreted interferon gamma (IFN-gamma) and tumor necrosis factor when stimulated with tumor cells in vitro. The effectiveness of TIL when adoptively transferred to mice bearing micrometastases correlated better with their ability to specifically secrete lymphokines than with their cytotoxicity in vitro. In 14 of 15 tests, therapeutically effective TIL specifically secreted IFN-gamma in vitro, whereas only 1 of 11 ineffective TIL specifically secreted IFN-gamma. In contrast, only 8 of 15 therapeutically effective TIL were cytolytic. Antibodies to TNF inhibited the effectiveness of two adoptively transferred TIL cultures. In five experiments, antibodies to IFN-gamma abrogated the ability of four different CD8+ TIL cultures to mediate tumor regressions, indicating that secretion of IFN-gamma is an essential part of the mechanism of action of TIL. PMID- 1900080 TI - Tumor necrosis factor is a critical mediator in hapten induced irritant and contact hypersensitivity reactions. AB - We examined the role of cytokines in the cutaneous response to the application of trinitrochlorobenzene (TNCB) in both nonsensitized and sensitized mice, i.e., in the irritant reaction (IR) and contact hypersensitivity reactions (CH). When administered immediately before challenge, anti-tumor necrosis factor (TNF) antibody abrogated the ear swelling response in CH; antibody directed against interferon gamma or antibodies to both granulocyte/macrophage colony-stimulating factor and interleukin 3 (IL-3) had a partial inhibitory effect; anti-IL-2 receptor antibody had no effect. Anti-TNF prevented the various features of the CH, as seen on histological sections, e.g., leukocyte infiltration and hemorrhages within the dermis and keratinocytes necrosis. Anti-TNF antibody also prevented the IR. The presence of TNF mRNA was evaluated on Northern blots; TNF alpha mRNA was detectable in an untreated ear, increased after the application of TNCB in nonsensitized mice, and was highest in sensitized mice. TNF mRNA accumulation, which was evident 0.5 h after hapten application and lasted greater than 72 h, was abolished by treatment with anti-TNF antibody, thus suggesting an auto-amplification of TNF production. The cellular origin of TNF mRNA was explored by in situ hybridization; basal keratinocytes showed the highest labeling, but TNF mRNA was also detectable in cells of the dermal infiltrate. After hapten (TNCB) application at sites susceptible (the ear) or resistant (the foot pad) to CH or IR, a close correlation was observed between TNF mRNA accumulation and the intensity of the inflammatory reaction. The major role played by TNF in both the CH and the IR explains the histologically similar aspects of these reactions and the extreme variability of these reactions at various anatomical sites. PMID- 1900081 TI - Virus-transformed pre-B cells show ordered activation but not inactivation of immunoglobulin gene rearrangement and transcription. AB - Virus-transformed pre-B cells undergo ordered immunoglobulin (Ig) gene rearrangements during culture. We devised a series of highly sensitive polymerase chain reaction assays for Ig gene rearrangement and unrearranged Ig gene segment transcription to study both the possible relationship between these processes in cultured pre-B cells and the role played by heavy (H) chain (mu) protein in regulating gene rearrangement. Our analysis of pre-B cell cultures representing various stages of maturity revealed that transcription of each germline Ig locus precedes or is coincident with its rearrangement. Cell lines containing one functional rearranged H chain allele, however, continue to transcribe and to rearrange the allelic, unrearranged H chain locus. These cell lines appear to initiate but not terminate rearrangement events and therefore provide information about the requirements for activating rearrangement but not about allelic exclusion mechanisms. PMID- 1900083 TI - Circular DNA resulting from recombination between V-(D)-J joining signals and switch repetitive sequences in mouse thymocytes. AB - During the course of analyzing circular DNA in mouse thymocytes, novel recombinants were identified with immunoglobulin heavy chain joining gene and switch region probes. These circles represent excision products of recombination between the heptamer-nonamer motif for V-(D)-J joining and a repetitive sequence for class switching. The molecular mechanisms that generate "hybrid circles" are discussed. PMID- 1900084 TI - Intrapulmonary growth and dissemination of an avirulent strain of Cryptococcus neoformans in mice depleted of CD4+ or CD8+ T cells. AB - The contribution of T lymphocyte subpopulations to intrapulmonary and systemic resistance against an opportunistic strain of Cryptococcus neoformans was examined. It was found that C. neoformans was destroyed when introduced into the lungs of normal mice, but disseminated to the brains of mice treated with an antibody that depleted them of CD4+ T cells. Depletion of either CD8+ or CD4+ T cells impaired the ability of the host to clear the yeast from the lung. These results, together with the observation that CD8+ T cells accumulate in the lungs of CD4+ T cell-deficient mice, suggest that CD8+ T cells play an important role in resistance to C. neoformans infection acquired via the respiratory tract. PMID- 1900086 TI - Comparison of implantation and early development of human embryos fertilized in vitro versus in vivo using transvaginal ultrasound. AB - Several reports in the literature suggest delayed implantation of in vitro fertilized human embryos compared to in vivo-fertilized eggs. The use of high frequency transvaginal transducers for early detection of pregnancy has allowed the identification of the gestational sac with very low serum human chorionic gonadotropin (beta-hCG) levels. Thus, the present study evaluated whether retarded implantation can be identified using this novel technology. We studied 13 single pregnancies after in vitro fertilization (IVF) and 14 pregnancies after artificial insemination either by husband (n = 6) or donor (n = 8). In the IVF patients, oocytes were retrieved 35 hours after hCG administration. Embryo transfer occurred approximately 48 hours after retrieval. Artificial insemination was performed 24 and 48 hours after hCG administration. Transvaginal ultrasound scans and serum beta-hCG levels were evaluated every 3 days starting day 12 post hCG administration. Serum beta-hCG levels rose in parallel when in vitro- and in vivo-fertilized embryos were compared. Similarly, there was no difference between groups in the mean time needed to detect early embryonic structures, such as the embryonic sac, yolk sac, and heartbeats, or the growth rate of the gestational sac. In conclusion, there was no difference in detecting implantation and early embryonic development of human embryos fertilized in vivo versus in vitro as ascertained by ultrasound scans and serum beta-hCG levels. An embryonic sac is detected 23-24 days after hCG administration in pregnancies achieved by assisted reproductive techniques. PMID- 1900082 TI - Characterization of somatically mutated S107 VH11-encoded anti-DNA autoantibodies derived from autoimmune (NZB x NZW)F1 mice. AB - We have studied 19 S107 heavy chain variable region gene (VH11)-encoded monoclonal antibodies from NZBWF1 mice. These studies show that a single VH gene can encode both antibodies to foreign antigens (anti-phosphorylcholine) and to self antigens (anti-double-stranded DNA) in the same animal. All of the anti-DNA antibodies contain many somatic mutations compared with the relevant germline genes. Since the anti-DNA antibodies were extensively somatically mutated and had undergone isotype switching, the response seems to be T cell dependent. While some of the antibodies appear to be the products of an antigen-driven and antigen selected response, a number of characteristics of the antibodies suggest that forces other than antigen are contributing to the stimulation and selection of this response. PMID- 1900085 TI - Phylogenetic relationships of Blepharisma americanum and Colpoda inflata within the phylum ciliophora inferred from complete small subunit rRNA gene sequences. AB - The complete small subunit rRNA gene sequences of the heterotrich Blepharisma americanum and the colpodid Colpoda inflata were determined to be 1719 and 1786 nucleotides respectively. The phylogeny produced by comparisons with other ciliates indicated that C. inflata is allied more closely with the nassophoreans and oligohymenophoreans than the spirotrichs. This is consistent with the placement of the colpodids in the Class Copodea. Blepharisma americanum was not grouped with the hypotrichs but instead was placed as the earliest branching ciliate. The distinct separation of B. americanum supports the elevation to class status given the heterotrichs based on morphological characters. PMID- 1900088 TI - A comparison of materials for the buildup of severely damaged teeth. PMID- 1900087 TI - In vitro study of the interaction of doxorubicin, thiotepa, and mitomycin-C, agents used for intravesical chemotherapy of superficial bladder cancer. AB - Several cytotoxic agents have been identified as effective in the treatment of superficial transitional cell carcinoma of the bladder, including doxorubicin, thiotepa and mitomycin-C. An in vitro study was conducted to assess the interactions of these three drugs against a well differentiated human bladder tumor cell line, RT-4, to identify and evaluate synergistic combinations among these agents. Cytotoxicity was evaluated by a colorimetric assay based on the capacity of viable cells to metabolize a tetrazolium dye, MTT, to produce a colored formazan product. The analyses of drug interactions were done by the isobolographic method (construction of isoeffect plots). The combination of doxorubicin and thiotepa was found to be the most synergistic, followed by the combination of doxorubicin and mitomycin-C. The combination of mitomycin C and thiotepa demonstrated an unpredictable effect. These findings suggest the combination of doxorubicin and thiotepa has potential advantage for chemotherapy of superficial bladder tumors. PMID- 1900089 TI - Cell cycle and clinical characteristics of patients with acute myeloid leukemia and myelodysplasia whose biopsies are reactive with anti-factor VIII antibody. A Leukemia Intergroup Study. AB - Presence of megakaryocytic cells in patients with myeloid disorders were investigated by staining plastic embedded biopsy sections with an anti-Factor VIII antibody (AFA). Two hundred and fifty cases were studied, 207 of whom had acute myeloid leukemia (AML) while 43 had myelodysplastic syndromes (MDS). Abnormal clusters of AFA positive cells indicating multilineage disease were identified in 17% with primary AML (30/175), 38% with secondary AML (12/32) and 42% cases of MDS (18/43). Biological characteristics of these 60 AFA positive cases were investigated. No unique differences in cell cycle characteristics following bromodeoxyuridine (BrdU) were identified. We confirm several recent reports that the incidence of multilineage involvement in AML is substantial. PMID- 1900090 TI - Kappa light chain gene rearrangement in a T-cell lymphoma. AB - Forty-three patients were studied to determine whether light chain gene rearrangements may occur in hematopoietic cells not pertaining to the B-lineage. In only one patient, affected by T-cell lymphoblastic lymphoma, one kappa light chain allele was rearranged. Neither at the protein level nor at the RNA level the rearranged gene was expressed. These data confirm that, although rarely, kappa light chain gene rearrangements may occur in neoplastic T-cells. Furthermore, as in our patient Ig heavy chain genes retained a germline configuration, the present data demonstrate that kappa light chain gene rearrangements may occur regardless of Ig heavy chain gene arrangement. PMID- 1900091 TI - Admission and mid-stay MedisGroups scores as predictors of hospitalization charges. AB - This study examines the ability of MedisGroups, a severity measure based on clinical data abstracted from the medical record, to predict hospitalization charges. MedisGroups measures severity both on admission and approximately 1 week into the hospital stay. The data base contained 23,361 admissions of Medicare beneficiaries in six conditions from 836 hospitals in seven states between January 1985, and May 1986. In all six conditions, higher admission and mid-stay severity scores were generally associated with higher charges. Across the six conditions, the R2 values for predicting charges using diagnosis-related group (DRG) class ranged from 0.06 to 0.32 using trimmed data. Adding admission MedisGroups scores to DRG class produced R2 values ranging from 0.09 to 0.33, while adding mid-stay scores yielded R2 values from 0.15 to 0.41, and adding both admission and mid-stay scores produced R2 levels ranging from 0.17 to 0.42. Very little of the superior predictive power of the mid-stay score could be attributed to its serving as a proxy for length of stay. PMID- 1900092 TI - Access to medical care. Monitoring changes in hospital utilization among elderly New York City residents. PMID- 1900093 TI - Comparison of three lasers for dental instrument sterilization. AB - The sterilization of dental instruments is an area of great interest and recent concern in the field of dentistry. The purpose of this study was to compare the ability of three lasers (argon, CO2, and NdYAG) to sterilize dental instruments. Endodontic reamers were contaminated with microorganisms, lased at various levels of energy, placed in Trypticase soy broth, incubated, and read for growth or no growth to determine sterility. Results indicated that the argon laser is capable of sterilizing selected dental instruments at the lowest energy level (1 watt for 120 seconds) of the three lasers tested. The other two lasers were able to sterilize the instruments also, but at higher energy levels. Results indicated all three lasers capable of sterilizing selected dental instruments; however, the argon laser was able to do so consistently at the lowest energy level of 1 watt for 120 seconds. PMID- 1900094 TI - Thermoregulatory and endocrine effects of a low dose of danazol in postmenopausal women: interaction with the effect of naloxone. AB - Before and on the 30th day of danazol administration (200 mg/day), in six postmenopausal women the activity of endogenous opioid peptides has been indirectly evaluated by the effect on LH secretion and body temperature (measured as rectal temperature) exerted by the infusion of the opioid antagonist naloxone (1.6 mg/h x 4 h preceded by 1.6 mg iv bolus). Before and during danazol administration a GnRH test (100 mcg iv bolus) was also performed to evaluate possible variations in pituitary responsiveness to GnRH. Danazol significantly reduced mean plasma levels of LH and FSH (p less than 0.01), and their response to GnRH stimulus (p less than 0.05). Either before or during danazol administration mean plasma LH and FSH levels did not vary during the infusion of naloxone, while body temperature significantly decreased (p less than 0.01). The decrease in body temperature was significantly greater (p less than 0.05) during danazol than before treatment. The present data suggest that in postmenopausal women a low dose of danazol exerts an antigonadotropic effect mainly reducing the pituitary responsiveness to GnRH. The enhanced hypothermic response to naloxone observed during danazol administration also seems to suggest that in postmenopausal women a low dose of danazol enhances the thermoregulatory role of endogenous opioid peptides. PMID- 1900095 TI - Increase in follicle stimulating hormone content occurs in cultured human fetal pituitary cells exposed to gonadotropin-releasing hormone. AB - To investigate the mechanisms by which GnRH regulates FSH production in the human fetus, dispersed pituitary cells from second trimester human fetuses were cultured on surface-modified plates. Exposure of cells to GnRH [(10(-8) and 10( 7) mol/L), study I] or [D-Ala6]des-Gly10-GnRH ethylamide (DALA) [(10(-11) to 10( 7) mol/L), study II] for 48 h resulted in an elevation of total FSH which correlated with an increase in releasable, but not nonreleasable, FSH. When pituitary cells were incubated for 24, 48 and 72 h with and without 10(-8) mol/L GnRH (study III), total FSH was significantly increased in cells cultured for 48 72 h without GnRH compared to cells lysed at the beginning of the incubation (p less than 0.001). At all intervals, GnRH significantly enhanced total FSH compared to respective controls (p less than 0.05). PMID- 1900097 TI - Lead poisoning among bricklayers--Washington State. AB - In May 1989, four members of an 11-man crew of bricklayers in western Washington state developed symptomatic lead poisoning while replacing the brick lining of an acid-accumulation tank at a paper mill. Peak blood lead levels (BLLs) for the four workers ranged from 88 to 123 micrograms/dL. An investigation indicated the source of the lead exposure was a special brick mortar that contained 71% lead oxide and was formulated to resist the normally acidic environment of the tank. PMID- 1900096 TI - Influence of muscle glycogen depletion on the rate of resynthesis. AB - In an effort to determine what effect the degree of muscle glycogen depletion has on the rate of resynthesis, six male cyclists completed an exercise protocol that involved both one- and two-legged cycling. One leg completed 30 min of single-leg cycling, ten one-min sprints, and 30 min cycling with both legs. This resulted in a large degree of depletion (LD). The contralateral leg completed only 30 min of double-leg cycling and experienced a small amount of depletion (SD). Following the exercise, the subjects rested quietly for 6 h and were fed a 24% carbohydrate (CHO) solution every 20 min in order to achieve a CHO intake of 0.7 g.kg-1.h-1. Biopsies taken from the vastus lateralis muscle immediately after exercise revealed that the glycogen content of the LD leg decreased 93.9 (+/- 11.6) mmol.kg-1 w.w., whereas the SD leg used 49.3 (+/- 5.7) mmol.kg-1 w.w. (P less than 0.01). Subsequent biopsies taken at 2 and 6 h of recovery demonstrated that the rate of muscle glycogen resynthesis was significantly greater in the LD leg, averaging 8.8 (+/- 2.4) mmol.kg-1.h1 w.w, while the SD leg restored glycogen at a rate of 3.0 (+/- 1.0) mmol.kg-1.h-1 w.w. (P less than 0.05). Glycogen synthase activity, expressed as its activity ratio (I/D), was also greater (P less than 0.01) in the LD leg both immediately after exercise (0.45 +/- 0.05 vs 0.24 +/- 0.04) and at 2 h of recovery (0.54 +/- 0.06 vs 0.27 +/- 0.06).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1900099 TI - Human rabies--Texas, 1990. AB - On June 5, 1990, a 22-year-old man died of rabies encephalitis in Hidalgo County, Texas, along the Mexican border. This was the fourth case of human rabies known to be acquired in the United States since 1980 and the first case in Texas since 1985. This report summarizes the case investigation. PMID- 1900098 TI - Transmission of multidrug-resistant tuberculosis from an HIV-positive client in a residential substance-abuse treatment facility--Michigan. AB - In November 1989, a man with a history of intravenous (IV)-drug use first presented to the tuberculosis (TB) clinic of the Muskegon County (Michigan) Health Department (MCHD). The patient indicated that he had been treated for pulmonary TB in another city, and he produced for clinic staff his labeled medications, which included isoniazid (INH), rifampin (RIF), and ethambutol (EMB). The patient also stated that he was an IV-drug user (IVDU) and previously had tested positive for human immunodeficiency virus (HIV) infection. Sputum specimens for acid-fast bacilli (AFB) were obtained, and the patient was maintained on his anti-TB medications. His HIV-antibody status was confirmed. PMID- 1900100 TI - NIOSH alerts on workplace hazards: falls through skylights and roof openings, deaths of farm workers in manure pits, and exposure to dimethylformamide. AB - CDC's National Institute for Occupational Safety and Health (NIOSH) periodically issues alerts on workplace hazards that have caused injury, illness, or death to workers. Three alerts are now available about the serious hazards posed by skylights and roof openings, manure pits, and the organic solvent dimethylformamide (DMF). Each alert is summarized briefly below. PMID- 1900102 TI - 1991: an "intense" year for the house of medicine. PMID- 1900103 TI - Medical preparedness for wartime. PMID- 1900101 TI - Mortality and morbidity in patients receiving encainide, flecainide, or placebo. The Cardiac Arrhythmia Suppression Trial. AB - BACKGROUND AND METHODS: In the Cardiac Arrhythmia Suppression Trial, designed to test the hypothesis that suppression of ventricular ectopy after a myocardial infarction reduces the incidence of sudden death, patients in whom ventricular ectopy could be suppressed with encainide, flecainide, or moricizine were randomly assigned to receive either active drug or placebo. The use of encainide and flecainide was discontinued because of excess mortality. We examined the mortality and morbidity after randomization to encainide or flecainide or their respective placebo. RESULTS: Of 1498 patients, 857 were assigned to receive encainide or its placebo (432 to active drug and 425 to placebo) and 641 were assigned to receive flecainide or its placebo (323 to active drug and 318 to placebo). After a mean follow-up of 10 months, 89 patients had died: 59 of arrhythmia (43 receiving drug vs. 16 receiving placebo; P = 0.0004), 22 of nonarrhythmic cardiac causes (17 receiving drug vs. 5 receiving placebo; P = 0.01), and 8 of noncardiac causes (3 receiving drug vs. 5 receiving placebo). Almost all cardiac deaths not due to arrhythmia were attributed to acute myocardial infarction with shock (11 patients receiving drug and 3 receiving placebo) or to chronic congestive heart failure (4 receiving drug and 2 receiving placebo). There were no differences between the patients receiving active drug and those receiving placebo in the incidence of nonlethal disqualifying ventricular tachycardia, proarrhythmia, syncope, need for a permanent pacemaker, congestive heart failure, recurrent myocardial infarction, angina, or need for coronary-artery bypass grafting or angioplasty. CONCLUSIONS: There was an excess of deaths due to arrhythmia and deaths due to shock after acute recurrent myocardial infarction in patients treated with encainide or flecainide. Nonlethal events, however, were equally distributed between the active-drug and placebo groups. The mechanisms underlying the excess mortality during treatment with encainide or flecainide remain unknown. PMID- 1900104 TI - Combat. PMID- 1900105 TI - Traveler's diarrhea in a West-Pac-deployed Navy/Marine Corps population. PMID- 1900106 TI - Infection control in the dental laboratory: a review of the literature. AB - The dental laboratory has been shown to be an area of potential disease transmission between patients and to laboratory personnel. This paper reviews pertinent literature on the subject and describes the "Barrier System," a proven infection control protocol to manage dental prostheses in the laboratory. PMID- 1900107 TI - A monitoring and evaluation study of third molar surgery complications at a major medical center. AB - This monitoring and evaluation study of third molar surgery complications took place over a 6-month period of time. The goal of the study was to determine complication rates following third molar extraction. A comparison was made between the staff's and residents' post-operative complication rates and patients receiving tetracycline powder in the extraction sockets vs. no antibiotics. Complication rates were compared in males vs. females, and in four different age groups. The study helped improve patient care by showing that alveolar osteitis rates decreased when all patients received topical tetracycline. It also confirmed that the experience of the surgeon, patient age, and gender influence complication rates. PMID- 1900108 TI - Perceptions of dentists' chairside behavior in a military dental care system. AB - A dental questionnaire was developed to assess patients' perceptions of dentists' chairside behavior in the military dental care system at Fort Carson, CO. Patients' perceptions of military and civilian dentists were found to be generally positive. No significant difference was found on the perceptions of civilian and military dentists in six of eight categories of personal behaviors involved in the chairside dentist-patient relationship. However, patients felt more rushed with civilian dentists and questioned more the necessity of dental work by civilian dentists. Nevertheless, patients appear to make minimal distinctions between these two groups, simply perceiving them as "the dentist." PMID- 1900109 TI - Oral health problems in Finnish conscripts. AB - The frequency of oral health problems in 353 Finnish conscripts aged 21.0 (SD 1.2 years) was studied by means of a questionnaire and by investigating the dental records. One hundred five (30%) conscripts had seeked dental help during their 8 months' military service. Forty-four percent of these patients had dental caries as their main diagnosis; endodontic problems comprised 9% of all cases. The problems related to third molars were second in frequency, accounting for 27% of the conscripts treated. Six and one-half percent of the patients had lost serving time on dental grounds (mean absence 3.6 days), most often (90%) due to acute pericoronitis or post-operative status following third molar surgery. PMID- 1900110 TI - Frostbite of the mouth: a case report. AB - A case report is presented of a young male who sustained a second-degree frostbite injury to the oral cavity, to include lower lip, hard palate, tongue, and buccal mucosa. This unusual injury occurred as a result of substance abuse: an attempt to inhale an aerosolized propane propellant as a means to achieve euphoria. PMID- 1900111 TI - Bilateral traumatic bone cysts of the mandible: an unusual clinical presentation. AB - This case report describes an unusual clinical presentation of bilateral traumatic bone cysts of the mandible. These lesions presented clinically as bilateral dentigerous cysts associated with the mandibular third molar teeth. Because of this unusual presentation, a combination of clinical examination, thorough history, radiographic studies, surgical exploration, and microscopic evaluation was necessary in order to render a definitive diagnosis on this case. Knowledge and awareness of these features are important to assist in the initial diagnosis as well as patient management and follow up. PMID- 1900112 TI - Consultation in the aftermath of an air tragedy. AB - In the early morning hours of December 12, 1985, a chartered jet airliner carrying 248 soldiers crashed shortly after takeoff, killing all aboard. The day after, the authors were designated as a consultation team to the mental health staff at Fort Campbell who were providing services in the aftermath of the crash. This report describes and analyzes the experiences of this consultation on disaster management. Our consulting experience has been one of the most profound and demanding events of our professional lives. Salient lessons of the consultation include: (a) the need to clarify leadership roles among the local mental health care team; (b) the need to help the local team establish clear roles among team members; (c) the value of enabling the local team to mourn the loss of their fellow soldiers and community members; and (d) the value of establishing a clear plan of mental health services for both short-term and long term management. PMID- 1900114 TI - Mental health issues related to the development of a national disaster response system. AB - With the creation of the National Disaster Medical System (NDMS), the federal government has moved to develop a national medical plan for responding to major mass casualty situations resulting from either a civilian disaster which overwhelms state and local resources or an overseas conventional conflict. To date, the mental health aspects of this plan have received little attention. This article discusses the rationale for adding a comprehensive mental health component to NDMS within the context of the complementary needs of disaster survivors and rescuers. PMID- 1900113 TI - Travelers' diarrhea among United States military personnel during joint American Egyptian armed forces exercises in Cairo, Egypt. AB - A study was conducted of travelers' diarrhea in a United States military population on deployment in Cairo, Egypt, during July and August 1987. Acute diarrhea requiring medical attention developed in 183 (4%) of 4,500 troops. A possible etiologic agent was identified in 49% of all diarrhea cases. Enteric pathogens associated with cases of diarrhea included: Enterotoxigenic Escherichia coli (17% ST-producers, 13% LT-producers, and 3% LT/ST-producers); Shigella (9%); Campylobacter spp. (2%); Salmonella (2%); and Vibrio cholerae non-01 serogroup (2%). Other enteric pathogens isolated from one episode each of diarrhea included Aeromonas hydrophila group, Plesiomonas shigelloides, and Bacillus cereus. Yersinia enterocolitica, enteroinvasive E. coli, intoxications by Clostridium perfringens and Clostridium difficile, and pathogenic enteric parasites were not found in any of the 183 patients with diarrhea. A survey of military personnel not requesting medical care indicated that up to 40% of troops may have had diarrhea during this deployment. Acute gastroenteritis is a potential cause of substantial morbidity in U.S. military personnel deployed to Egypt. PMID- 1900115 TI - What makes war surgery different? AB - How can our military surgeons be optimally prepared for their roles in the combat setting? The recent training assignment of military surgeons to urban trauma centers is a necessary first step toward this elusive goal, although not conclusive preparation for carrying out surgery in a combat theater. The multiple dimensions of difference between combat and peacetime medical practice require continuing emphasis. PMID- 1900116 TI - Veterinary care of the Belgian Malinois military working dog. AB - The Belgian Malinois dog was introduced into the Department of Defense Military Working Dog Program in 1984. All dogs are purchased in Europe and have adapted well to the rigorous training requirements of the program. Most veterinary problems seen in this breed are related to kennel confinement and include traumatic dental disease, tail lesions, a variety of dermatologic conditions, and an inability to gain weight. Epilepsy is a breed problem and has been seen in this population, as has gastric dilatation/volvulus. Both elbow and hip dysplasia exist in the Malinois breed. PMID- 1900117 TI - Perforation by a foreign body through a pre-existing radial keratotomy wound. AB - A case is presented demonstrating selective perforation of a foreign body through a pre-existing partial thickness radial keratotomy wound. This is the initial documentation of a distinct type of injury to which an eye is susceptible following corneal refractive procedures. Despite the excellent outcome, the occurrence of this injury in a soldier during a field training exercise provides additional justification for current Army policy of barring the induction of enlistees who have undergone corneal surgery to correct refractive errors. PMID- 1900119 TI - Photic maculopathy in young males with intraocular foreign body. AB - A young male with intraocular foreign body (IOFB) and clear media had successful removal of the IOFB but sustained macular damage and permanent loss of vision secondary to operating microscope phototoxicity. Light damage to the eye can be thermal, mechanical, or photochemical and is dependent on source and wavelength of light, filters, and host factors. Removal of IOFB is important, but surgeons must be aware of potential light damage to the macula in lengthy surgical procedures and take appropriate precautions. PMID- 1900120 TI - Are you ready to deploy? PMID- 1900118 TI - Cellulitis and compartment syndrome due to Plesiomonas shigelloides: a case report. AB - We report a case of cellulitis, compartment syndrome, and septicemia associated with fish handling. The etiologic pathogen isolated from the wound and blood cultures was Plesiomonas shigelloides. The pathogen can cause serious illness in people handling fish. PMID- 1900121 TI - Infection control of field dental units. AB - The need for infection control procedures exists for dental care provided outside of dental treatment facilities. In a wartime scenario or during military training exercises, traditional dental clinic settings may not be available and the dental officer will be required to treat patients using equipment provided by the Army's Table of Organization and Equipment. This article reviews the dental literature and makes recommendations to aid the dental officer in developing an infection control protocol for field dental equipment. PMID- 1900122 TI - Charting accuracy in Navy dental records. AB - Eighty-five Navy patients and their dental records were reviewed, to determine the accuracy of the recorded initial findings in the SF603 Dental Record, and any subsequent treatment recordings. These findings were compared to those of a similar study published in 1970, and comparisons were drawn between the two reviews as to the accuracy of the charting and usefulness for forensic dental identification. A possible future concern in forensic dental identification was identified and is discussed. PMID- 1900123 TI - Efficacy and long-term effects of antenatal prophylaxis with anti-D immunoglobulin. PMID- 1900124 TI - Ifosfamide and mesna for the treatment of advanced squamous cell head and neck cancer. A GETLAC study. AB - High-dose ifosfamide/mesna was administrated to 28 mostly pretreated patients with locally advanced and metastatic head and neck cancer who failed conventional surgery/radiation treatment. Primary sites include tongue (5), salivary gland (3), floor of mouth (5), oropharynx (2), hypopharynx (5) and larynx (8). The dose and schedule of ifosfamide (IF) was 3.5 g/m2 8 h, i.v. infusion, days 1-5, every 28 days, and mesna was given as 20% of IF dose intravenous bolus injection at 0, 2, 4, 6 and 8 h; mesna 40% of IF dose was given by oral route at 10 and 12 h, days 1-5, every 28 days. All patients were evaluable for both toxicity and response. 14 patients had received prior treatment with surgery plus radiation therapy and 14 patients radiation therapy. Following chemotherapy, 4 patients (14.2%) achieved complete remission and 8 patients (28.5%) achieved partial remission, with an overall response rate of 42.7%. Toxicity was reported for 186 cycles and ranged from mild to moderate: anemia 4, leukopenia 6, thrombopenia 1, nausea and vomiting 12, alopecia 28, microscopic hematuria 3, increased transaminase 1. No CNS symptoms and renal toxicity were registered. Median duration of survival is 11+ months (range 3+ to 18+ months). Nine patients died. We conclude that ifosfamide/mesna at this dose and schedule has a significant activity in recurrent head and neck cancer, and produces minimal toxicity. PMID- 1900125 TI - Heterotopic ossification. AB - Heterotopic ossification is a frequently encountered orthopaedic condition with multiple etiologies. Although not commonly problematic, it can be a devastating complication. Prophylactic measures, early recognition, and appropriate treatment are paramount in the management of this disorder. This article presents a review of the literature, delineates predisposing factors and identification of high risk patients, and discusses current modes of prophylaxis and treatment of neurogenic and postoperative heterotopic bone formation. PMID- 1900126 TI - Physiologic role of heme and cytochrome P-450 in hematopoietic cells. PMID- 1900127 TI - Time-related distribution profiles of sulfated glycosaminoglycans in cells, cell surfaces, and media of cultured rat liver fat-storing cells. AB - Fat-storing cells (perisinusoidal lipocytes, Ito cells), the principal proteoglycan-producing cell type in liver, were maintained for various times in primary and secondary culture to monitor the amount and pattern of [35S]sulfate labeled glycosaminoglycans (GAG) in the cells, on the cell surface, and in the medium. In parallel with the phenotypic modulation of fat-storing cells toward myofibroblast-like cells, intracellular GAG decrease progressively, whereas cell surface-bound and medium GAG increase several-fold. These changes are associated with time-dependent alterations of the pattern of GAG in the various compartments. Dermatan sulfate is the most prominent intracellular GAG type in primary cultures, but on the cell surface and in the medium chondroitin sulfate prevails and reaches almost 70% of all medium GAG in secondary cultures. The results point to a highly dynamic expression of the specific types of GAG in the cellular and extracellular compartments of fat-storing cell cultures that seems to accompany the spontaneous transformation into myofibroblast-like cells. The latter one is a mainly chondroitin sulfate-producing cell type, whereas the initial fat-storing cell generates predominantly dermatan sulfate. PMID- 1900128 TI - Regulation of intracellular pH in glomerular mesangial cells. PMID- 1900129 TI - Properties of the renal Na(+)-HCO3- cotransporter. PMID- 1900130 TI - Molecular nature of the Drosophila sex determination signal and its link to neurogenesis. AB - In 1921 it was discovered that the sexual fate of Drosophila is determined by the ratio of X chromosomes to sets of autosomes. Only recently has it been found that the X chromosome to autosome (X:A) ratio is communicated in part by the dose of sisterless-b (sis-b), an X-linked genetic element located within the achaete scute complex of genes involved in neurogenesis. In this report, the molecular nature of the primary sex determination signal and its relation to these proneural genes was determined by analysis of sis-b+ germline transformants. The sis-b+ function is confered by protein T4, a member of the helix-loop-helix family of transcription factors. Although T4 is shared by sis-b and scute-alpha, the regulatory regions of sis-b, which control T4 expression in sex determination, are both separable from and simpler than those of scute-alpha, which control T4 expression in neurogenesis. Dose-sensitive cooperative interactions in the assembly or binding of sis-dependent transcription factors may directly determine the activity of the female-specific promoter of Sex lethal, the master regulator of sexual development. In this model there is no need to invoke the existence of analogous autosomal negative regulators of Sex lethal. PMID- 1900131 TI - Molecular transfer of a species-specific behavior from Drosophila simulans to Drosophila melanogaster. AB - Drosophila males modulate the interpulse intervals produced during their courtship songs. These song cycles, which are altered by mutations in the clock gene period, exhibit a species-specific variation that facilitates mating. We have used chimeric period gene constructs from Drosophila melanogaster and Drosophila simulans in germline transformation experiments to map the genetic control of their song rhythm difference to a small segment of the amino acid encoding information within this gene. PMID- 1900132 TI - Mutants from V79 fibroblasts exhibiting hypersensitivity to aphidicolin and 3' azido-3'-deoxythymidine. AB - One variant, aphhs-3 was previously isolated based on a hypersensitivity to nontoxic concentrations of aphidicolin, a specific inhibitor of DNA polymerases alpha and delta. This variant was found to be more sensitive to temperatures above 35 degrees C and to 10 microM of 3'-azido-3'-deoxythymidine (zidovudine, azidothymidine, or AZT) than the parental 743x cells. DNA polymerase activities in the cell extract or in the partially purified fraction by DEAE-cellulose (DE52) anion exchange column from aphhs-3 were active at 40 degrees C. No significant differences in deoxynucleoside triphosphate pools were observed at 34 degrees C for both the parental 743x and aphhs-3 cells. Revertants were isolated at 39 degrees C: six revertants (aphhs-3-tr1 through aphhs-3-tr6) were obtained without aphidicolin; one revertant aphhs-3-tar (the tar clone) was selected in aphidicolin (0.12 microM). The hypersensitivity to aphidicolin (Aphhs) and AZT (AZThs) was cosegregated in the revertant aphhs-3-tr5 (the tr5 clone), while the tar clone was not AZThs. There was a similar increase in the specific activity of 3H-labeled DNA in all cell lines after additions of [3H]AZT or [3H]thymidine. Additions of purine or pyrimidine arabinosides (araT, araC, and araA) to all cell lines resulted in a similar cytotoxicity, suggesting the anabolism of dTTP was not defective in the tr5 clone. The spontaneous mutation rate at the hypoxanthine guanine phosphoryltransferase locus using replating techniques and 6-thioguanine resistance selection was less than or equal to 5 x 10(-7), 2.2 x 10(-6), or 1.3 x 10(-6) per generation for the tr5, 743x, or tar cell lines, respectively. Most importantly, DNA polymerase activities in the cell extract of the revertant tr5 clone were inhibited by 0.5 microM AZTTP. In contrast, no inhibition was observed in those of the parental 743x and revertant tar cells. The cosegregation of both Aphhs and AZThs in the tr5 revertant suggests that these two phenotypes may be a result of the same mutational event. PMID- 1900133 TI - Differential mRNA stabilities affect mRNA levels in mutant mouse myeloma cells. AB - A series of mouse myeloma cell lines producing mutant gamma 2b immunoglobin heavy chains, which resemble heavy chain disease proteins, were analyzed for messenger RNA abundance as a function of mRNA alterations. A mutation effectively deleting the gamma 2b-CH1 domain of the mRNA had little or no effect on Ig heavy chain mRNA abundance on half-life (mutant 10.1). A mutation in the gamma 2b-CH2 and CH3 domain, causing premature termination of translation, had more deleterious effects on Ig heavy chain mRNA abundance and half-life (mutant I17). Substitution of the deleted portions of the gamma 2b mRNA with gamma 2a sequences by subclass switching in the cells (mutants K23 and K25) resulted in increased heavy chain abundance and half-life relative to the parent I17. In contrast, kappa light chain mRNA levels and half-lives remain constant among the mutants. The wild-type and mutant cell lines transcribed the Ig heavy chain gamma 2b locus equally when compared with an internal beta-actin standard by transcription run on studies. Therefore, half-life of the Ig heavy chain mRNA seems to be the principal determinant in cytoplasmic mRNA abundance in this system. PMID- 1900134 TI - Assignment of human preprothyrotropin-releasing hormone (TRH) gene to chromosome 3. AB - The human gene encoding preproTRH (thyrotropin-releasing hormone) was assigned to chromosome 3, using human-Chinese hamster ovary somatic cell hybrids, analyzed by Southern hybridizations. Hybridization was carried out with a 32P-labeled human preproTRH cDNA labeled by the method of random priming. Hybridization of the cDNA probe to a human specific 4.8-kb DNA fragment of EcoRI-digested WBC DNA was used to localize the human preproTRH gene. No hybridization, by contrast, was seen with human preproTRH cDNA probe and hamster DNA after EcoRI treatment. Results from 29 somatic cell hybrids corroborated unequivocally that the human preproTRH gene can be assigned to human chromosome 3. PMID- 1900135 TI - Hospital costs, resource characteristics, and the dynamics of death for general surgery patients. AB - The world of health care finance and quality assessment is undergoing rapid change. We analyzed a large group of general surgical patients who died regarding hospital resource consumption. General surgical patients who died generated much greater resource consumption than survivors per DRG; increasing hospital LOS for general surgical patients who died was associated with increasing financial risk under DRGs. Patients who died after non-emergency admission generated similar financial risk to patients who died after emergency admission. General surgical patients who died who were referred from another clinical service generated, on average, similar resource consumption to non-referred patients who died. The results of this study support those of previous studies suggesting the payment inequities of DRGs for general surgical patients who die and suggest that attention should be directed at improving the DRG hospital payment system for these patients. PMID- 1900137 TI - [Ambulance helicopters in the mountains. An evaluation of the 1-year activity at the Dombas base]. AB - On 1 January 1988 the Norwegian Air Ambulance Plan was put into effect. The operational base for the regional counties Oppland, parts of South Trondelag, More and Romsdal and Hedmark was established in the township of Dombas. The base had a helicopter staffed with a specialist in emergency medicine. The operation of this base was evaluated for the period 1 February 1988 to 1 February 1989. 242 missions were undertaken. In 27 of 184 primary missions (15%) and in 11 of 32 secondary missions (33%) the service was judged to have given health benefit. It may have prevented the death of 13 patients. The service costs during the year were approximately NOK 10 million. The cost-benefit ratio is judged to be too high. In inland-Norway, with a widely scattered population, it is probably better to improve the quality of the emergency services offered by general practitioners and ordinary road ambulances than to use a helicopter staffed with a specialist in emergency medicine. PMID- 1900136 TI - Perioperative care of the pediatric patient. PMID- 1900138 TI - Time-course effects of ethanol pretreatment on hepatic necrosis and fat accumulation induced by aflatoxin B1 in the rat. AB - Effect of ethanol pretreatment on acute hepatotoxicity and hepatic fat accumulation induced by aflatoxin B1 (AFB1) was followed up to 120 h in male Wistar rats. Pretreatment with 4 oral doses of ethanol (4.0 g/kg body wt. each) at 48, 45, 24 and 21 h prior to AFB1 (2.0 mg/kg body wt.) single intraperitoneal administration caused a significant increase in the activity of plasma glutamic oxaloacetic transaminase (PGOT, 2.4-fold), plasma glutamic pyruvic transaminase (PGPT, 2.8-fold), liver triglycerides (2.3-fold) and the severity of liver necrosis at 72 h after AFB1 administration. The effect of ethanol pretreatment on an increase in the accumulation of liver cholesterol and cholesterol esters induced by AFB1 is additive in nature. In a time-course study, it was shown that liver necrosis and triglyceride, cholesterol and cholesterol ester accumulation occurred simultaneously in both groups of rats treated with AFB1 and ethanol AFB1. These results suggest that fat accumulation per se is not a primary cause of liver necrosis induced by AFB1 and ethanol-AFB1. PMID- 1900139 TI - Pericardial effusion after intravenous recombinant tissue-type plasminogen activator for acute myocardial infarction. AB - The effect of thrombolytic therapy on the frequency, time course and sequelae of pericardial effusion after myocardial infarction are unknown. A prospective, serial, 2-dimensional echocardiographic study of patients with myocardial infarction who received recombinant tissue-type plasminogen activator (rt-PA) was undertaken to address this issue. The study population comprised 52 of the 112 patients enrolled in the first Thrombolysis and Angioplasty in Myocardial Infarction trial at Duke University Medical Center. Enrollment in the serial echocardiography protocol was determined by equipment and support staff availability. Complete echocardiographic studies were performed within 90 minutes after initiation of thrombolytic therapy (day 0), and on days 1, 3 and 6. Patients undergoing serial echocardiography did not differ in demographic or clinical characteristics from those who did not. Pericardial effusion was present in 3 of 38 patients (8%) at day 0, in 2 of 44 (5%) at day 1, in 8 of 43 (19%) at day 3, and in 10 of 42 (24%) at day 6. By day 6, 3 of 10 pericardial effusions were moderate in size, 1 of 10 was large and the remainder were small. No patients developed echocardiographic or hemodynamic signs of cardiac tamponade. The prevalence and time course of pericardial effusion among patients with acute myocardial infarction who received rt-PA in this study are similar to observations reported in earlier studies in which patients did not receive thrombolytic therapy. Adverse sequelae of pericardial effusion after thrombolytic therapy are rare. PMID- 1900140 TI - Impaired hepatic function tests after thrombolysis for acute myocardial infarction. PMID- 1900141 TI - Controversies, dilemmas, and dialogues. What do you recommend for prophylaxis in an elderly woman with arthritis requiring NSAIDs for control? PMID- 1900142 TI - IgA antigliadin antibodies, cellobiose/mannitol sugar test, and carotenemia in the diagnosis of and screening for celiac disease. AB - Serum IgA antigliadin antibodies (IgAAGA) assay, cellobiose/mannitol sugar permeability test (ST), and carotenemia were evaluated prospectively as diagnostic tests in 60 consecutive adult patients with suspected celiac disease (CD). CD was confirmed histologically in 26 patients. IgAAGA, ST, and carotenemia had a sensitivity of 65.4%, 96.2%, and 76.9%, a specificity of 97.1%, 73.5%, and 70.6%, and positive likelihood ratio of 22.2, 3.6, and 2.6, respectively. Multivariate logistic regression showed that IgAAGA and ST had a sensitivity and specificity of 96.2% and 70.6% and a positive likelihood ratio of 47.3 if both were positive. Assuming a prevalence of CD of 1:2000 in the general population, for every 89 positive IgAAGA and 549 altered ST there would be one celiac patient, whereas, if both tests were positive, the patient was certain to have CD. We conclude that, of the tests studied, IgAAGA and ST are respectively the most specific and the most sensitive and that, used together, they can diagnose CD. PMID- 1900143 TI - Nutritional support in Crohn's disease: which route? AB - Nutritional and clinical responses to three nutritional regimens were retrospectively evaluated in 81 Crohn's patients with active disease. Group 1 (n = 42) received a low residue oral diet, group 2 (n = 15) received chemically defined diets, and group 3 (n = 24), parenteral nutrition (PN). Weight gain was observed in a similar percentage of patients, whereas serum albumin increase was significant only in group 3: 3.15 +/- 0.66 versus 3.54 +/- 0.61 g/100 ml (p less than 0.05). Mean activity index decreased significantly in all groups (p less than 0.001), and length of stay in hospital was similar. Patients with intestinal obstruction had a better immediate response when submitted to PN: clinical remission was achieved in 75% of those in group 3, but in only 50% in groups 1 and 2 (p less than 0.05). Otherwise, short- and long-term outcome was similar. PMID- 1900144 TI - A case of gastric plasmacytoma: genetic analysis and immunofixation electrophoresis. AB - A case of early gastric plasmacytoma in a 66-yr-old woman is reported. The demonstration of monotypic IgM lambda immunoglobulin in plasma cells infiltrating the gastric antrum contributed the histological diagnosis. Genetic analysis of the tumor cells confirmed the presence of a monoclonal neoplastic population of plasma cells in the tumor. Monoclonal immunoglobulin (IgM lambda) was demonstrated in serum, not by conventional immunoelectrophoresis, but by a highly sensitive immunofixation electrophoresis technique. Serum monoclonal immunoglobulin disappeared after subtotal gastrectomy. The value of immunofixation electrophoresis of serum protein and DNA analysis of tumor cells was emphasized for the diagnosis of gastric plasmacytoma. PMID- 1900146 TI - Nurses seek a voice in right-to-die cases. PMID- 1900145 TI - Km typing with PCR: application to population screening. AB - The immunoglobulin kappa light chain (IgK) locus may play a significant role in the pathology of both infectious and autoimmune diseases. Most of the work on IgK genetics has been conducted using immunological techniques for allelic typing and sequence analysis. This is restricted by availability of reagents and can be both expensive and time-consuming. PCR primers were designed to amplify the kappa constant gene (Ck), and four allele-specific oligonucleotides (ASOs) were used to distinguish the alleles in the amplified PCR products. Direct sequencing of PCR products was performed to confirm that the primers specifically amplified the Ck region and the ASOs differentiated the Km alleles. Sequencing of an average of 209 nucleotides of DNA from 50 individuals revealed no variation except at codon 191, which is known to be involved in a frequent polymorphism. An analysis of 347 different individual DNAs from 10 human populations was conducted to determine Km allelic frequencies within these populations and to apply this type of data collection to population studies. PMID- 1900147 TI - Return to independence. Lessons from a hospital long-term care unit. PMID- 1900148 TI - Mitomycin C as an adjuvant treatment to resected gastric cancer. A 10-year follow up. AB - Seventy consecutive patients were entered in a two-arm randomized trial after surgical resection for locally advanced gastric cancer. In the first arm, 37 patients were included as a control group, receiving no further treatment after surgery. In the second arm, 33 patients were treated with adjuvant chemotherapy consisting of mitomycin C (MMC), 20 mg/m2 administered intravenously once every 6 weeks for four consecutive cycles. All patients in both arms were followed in the same way for 5 years. At 5 years 23 of 37 patients in the control arm and 7 of 33 patients in the treatment arm were dead because of relapse. Actuarial survival curve was statistically significant in favor of patients given adjuvant MMC (p less than 0.001). After 10 years follow-up, 31 of 37 patients in the control arm and 16 out of 33 patients in the treatment arm were dead because of relapse, the statistical differences continuing in the actuarial survival curve in favor of treated patients (p less than 0.01). The best advantages of adjuvant treatment were observed in the T3N0M0 stage. The most frequent relapse site was the peritoneal cavity and the relapse pattern shows special decrease in liver metastases in treated patients. Toxicity was acute and mild. No delayed toxicity or second malignancies were observed. These data suggest that adjuvant MMC after resected surgery of gastric cancer is a successful treatment and its effects are still evident after 10 years of follow-up. PMID- 1900149 TI - End-to-end repair of aortic coarctation using absorbable polydioxanone suture. AB - Based on previous laboratory work, we have used polydioxanone absorbable suture in a variety of vascular and cardiac repairs in pediatric patients. However, some investigators have expressed concern about the potential for aneurysm formation at the anastomotic site. Between March 1983 and June 1989, 15 patients (7 male, 8 female) aged 2.5 months to 9.2 years (mean, 3.7 years) had resection of coarctation of the aorta and end-to-end anastomosis with polydioxanone absorbable suture. Thirteen patients have returned for routine postoperative evaluation, the follow-up time ranging from 11 to 49 months (mean, 23 months). Noninvasive two dimensional, pulsed-wave Doppler and color echocardiography and magnetic resonance imaging studies demonstrated good anatomical repair and no anastomotic aneurysm formation or residual coarctation of the aorta in any patient after end to-end anastomosis with polydioxanone. In summary, this intermediate follow-up study has revealed no vascular complications related to the repair of coarctation with absorbable polydioxanone suture. PMID- 1900150 TI - Diagnostic imaging of heterotopic ossification with coexistent deep-venous thrombosis in flaccid paraplegia. AB - Heterotopic ossification and deep-venous thrombosis can coexist. This raises potential problems because diagnosis depends heavily on imaging studies, and an ideal imaging study which will cost-effectively and noninvasively diagnose both conditions simultaneously is not readily available. A case of coexistent heterotopic ossification and deep-venous thrombosis in flaccid paraplegia is presented. In this case, deep-venous thrombosis and pulmonary embolus were diagnosed and treatment was begun without knowledge of the coexistent heterotopic ossification. Alternative imaging and laboratory diagnostic strategies are discussed. It was concluded that, at this time, clinical acumen and judicious use of traditional diagnostic alternatives is the best means of selecting appropriate treatment. Awareness of the coexistence of the two conditions are careful attention to the patient's clinical course can minimize treatment delays and resultant morbidity. PMID- 1900151 TI - Protease nexin-2/amyloid beta-protein precursor in blood is a platelet-specific protein. AB - The protease inhibitor, protease nexin-2 (PN-2), is the secreted form of the amyloid beta-protein precursor (APP) which contains the Kunitz protease inhibitor domain. PN-2/APP is an abundant platelet alpha-granule protein which is secreted upon platelet activation. PN-2/APP mRNA is present in cultured endothelial cells and the protein has been detected in plasma. In the present studies we quantitated PN-2/APP in platelets, plasma and several different cell types of the vasculature to identify the repository of the protein in the circulatory system. We report that PN-2/APP is predominantly a platelet protein in the vascular compartment. Lysates of unstimulated umbilical vein endothelial cells, granulocytes or monocytes contained little PN-2/APP based on sensitive functional protease binding and immunoblotting assays. Quantitative immunoblotting studies demonstrated that normal citrated-plasma contains less than or equal to 60 pM PN 2/APP. In contrast, platelets can contribute up to 30 nM PN-2/APP, indicating that they are the major source of the protein in blood. PMID- 1900152 TI - Tissue and subcellular distributions of an inhibitory GDP/GTP exchange protein (GDI) for the rho proteins by use of its specific antibody. AB - We have recently purified from bovine brain cytosol to near homogeneity a GDP/GTP exchange protein for the rho proteins, named rho GDI, that inhibits the dissociation of GDP from and the subsequent binding of GTP to the rho proteins. In the present study, we made a monoclonal antibody against rho GDI and studied its tissue distribution in rat and its subcellular distribution in rat cerebrum by use of this antibody. rho GDI was found in most rat tissues as described for the rho proteins. In rat cerebrum, rho GDI was mostly found in the cytosol of neuron body and synaptosome. In synaptosome, it was mainly found in the synaptic cytosol. PMID- 1900153 TI - Phosphorylation of basic fibroblast growth factor by purified protein kinase C and the identification of a cryptic site of phosphorylation. AB - We have further characterized the protein kinase C (PK-C) dependent phosphorylation of basic fibroblast growth factor (FGF). Intact recombinant basic FGF and a series of ten peptide fragments of basic FGF were phosphorylated by PK C and the products were analyzed by SDS-PAGE and autoradiography. As expected, peptide fragments containing the known site of phosphorylation (Ser64) are substrates for phosphorylation. Surprisingly however, peptides containing the receptor binding domain of the mitogen [basic FGF(106-115)] are also phosphorylated. An examination of this sequence reveals the presence of a consensus sequence (Ser108-Ala109-Lys110) that mediates the reaction. Accordingly, all peptides that contain the core amino acids basic FGF(106-111) are substrates for phosphorylation. Peptide mapping of basic FGF confirms that Ser64 is the primary site of phosphorylation, suggesting that Ser108 is a cryptic consensus sequence. Because basic FGF is metabolized to sequence specific fragments after its binding and internalization into target cells, this cryptic site may in fact be phosphorylated in vivo. PMID- 1900154 TI - Role of a guanine nucleotide binding protein, G alpha 2, in regulation of adenylate cyclase in Dictyostelium discoideum. AB - Two substances, cAMP and 2,3-dimercapto-1-propanol (BAL) are known to induce transient activation of adenylate cyclase in Dictyostelium discoideum. A frigid mutant (HC85) has a deletion in a gene for G alpha 2, a guanine nucleotide binding protein and cannot activate the cyclase in response to cAMP. We found that BAL induced activation in the frigid mutant. This result suggests that the BAL-induced activation is independent of G alpha 2 and that BAL mimics a role of activated G alpha 2. We also found that cAMP promoted the BAL-induced activation. This result suggests that cAMP plays a role in activation through a mechanism in which G alpha 2 is not involved. We lastly showed that continuous cAMP stimulation could not inhibit the BAL-induced activation in the frigid mutant. Since the cAMP-induced inhibition observed in the wild type strain (NC4) proceeds with the time course identical to the cAMP-induced adaptation (Oyama, submitted), this result suggests that G alpha 2 is involved in adaptation of adenylate cyclase. PMID- 1900155 TI - Jun-B gene expression mediated by the surface immunoglobulin receptor of primary B lymphocytes. AB - Stimulation of primary B lymphocytes induces the nuclear expression of TPA response element binding proteins that are recognized by anti-Jun antisera. To evaluate the profile of jun gene expression, RNA was extracted from B cells and probed for c-jun. Surprisingly, c-jun mRNA was not detected either before or after stimulation with anti-Ig. Instead, stimulation through the sIg antigen receptor, or with phorbol ester containing regimens, rapidly induced expression of the related jun-B. This demonstrates a lack of coordinate regulation for jun-B and c-jun expression in these primary B cells. The role of Jun-containing TRE binding proteins in promoting B cell cycle progression remains uncertain inasmuch as Jun-B has been associated with transcriptional inhibition of the TPA response element, rather than activation as produced by c-Jun. PMID- 1900156 TI - Inhibitory effects of two structurally related carbocyanine laser dyes on the activity of bovine heart mitochondrial and Paracoccus denitrificans NADH ubiquinone reductase. Evidence for a rotenone-type mechanism. AB - Two cationic, lipophilic laser dyes, 1,1',3,3,3',3'-hexamethylindodicarbocyanine iodide (HIDC) and 1,1',3,3,3',3'-hexamethylindotricarbocyanine iodide (HITC), inhibit bovine heart mitochondrial and Paracoccus denitrificans NADH oxidase activities. The mitochondrial I50 values were 0.5 microM (HIDC) and 1.2 microM (HITC), and the P. denitrificans I50 values 1.2 microM (HIDC) and 1.5 microM (HITC). Neither succinate nor cytochrome oxidase (EC 1.9.3.1) activities were inhibited significantly by either compound, localizing the site of inhibition to the segment of each electron transport chain between NADH and ubiquinone. With submitochrondrial particles (SMP), NADH-dependent reduction of menadione, duroquinone and coenzyme Q1 was inhibited markedly (HIDC was the more potent inhibitor). Using purified complex I, only NADH-dependent reduction of duroquinone and coenzyme Q1 was inhibited markedly (HIDC was the more potent inhibitor) and reduction of menadione was inhibited slightly. With P. denitrificans membrane vesicles, NADH-dependent reduction of menadione, juglone, and coenzyme Q1 was inhibited slightly and duroquinone reduction was inhibited markedly. Membrane-dependent interactions appear to be involved, since the compounds were more inhibitory with membrane preparations than with complex I. The mechanism of inhibition (except for the HIDC effect on coenzyme Q1 reduction with P. denitrificans) appeared to be through the interaction of dye with the rotenone site on NADH-ubiquinone reductase (EC 1.6.99.3), since rotenone insensitive preparations of complex I and P. denitrificans membrane vesicles were also insensitive to HIDC and HITC inhibition. PMID- 1900157 TI - Correlation between oxidation of low density lipoproteins and prostacyclin synthesis in cultured smooth muscle cells. AB - The effect of antioxidants on the oxidation of low density lipoproteins in relation to prostacyclin synthesis was investigated in the prescence of rabbit smooth muscle cells (SMC) and Fe-containing culture medium. The lipid peroxidation of low density lipoproteins (LDL) assayed as thiobarbituric acid reactive substances was increased from 0.5 to 1.4 nmol malondialdehyde/mL by the presence of smooth muscle cells. Two potent antioxidants, nordihydroguairetic acid (NDGA) and butylated hydroxytoluene (BHT), inhibited lipoprotein oxidation by IC50 values of 0.2 and 0.8 microM, respectively. Inhibition of lipoprotein oxidation was associated with an increased prostacyclin synthesis by the SMC, the effect being more pronounced with nordihydroguairetic acid than with butylated hydroxytoluene. The stable metabolite of the lipid hydroperoxide, 15 hydroxyeicosatetraenoic acid (15-HETE), formed in the 15-lipoxygenase pathway was measured following antioxidant treatment and found to be eliminated or greatly reduced by both antioxidants. The results presented show that lipid hydroperoxides, formed as a consequence of lipoprotein oxidation and promoted by the smooth muscle cells through a lipoxygenase reaction, may regulate prostacyclin synthase, a process which may be influenced by the addition of antioxidants. PMID- 1900159 TI - Assessment of the drug inhibitor specificity of the human liver 4 methylumbelliferone UDP-glucuronosyltransferase activity. AB - The data suggest that the 4MU-UDPGT activity of human liver microsomes probably contributes to the glucuronidation of a limited number of clinically used drugs. However, confirmation of this ultimately requires studies to be performed with purified isozymes, cDNAs expressed in cell culture, or specific inhibitory antibodies. PMID- 1900158 TI - Efficacy of combination therapy with tubercidin and nitrobenzylthioinosine 5' monophosphate against chronic and advanced stages of schistosomiasis. AB - The efficacy of the highly selective antischistosomal combination chemotherapy with tubercidin (7-deazaadenosine) plus nitrobenzylthioinosine 5'-monophosphate (NBMPR-P), [el Kouni et al., Proc Natl Acad Sci USA 80: 6667-6670, 1983; el Kouni et al., Biochem Pharmacol 36: 3815-3821, 1987] was examined against chronic and advanced stages of schistosomiasis in mice. Administration of four successive daily doses of tubercidin (5 mg/kg/day) plus NBMPR-P (25 mg/kg/day) to Schistosoma mansoni-infected mice beginning 5, 6, 7 and 8 weeks post-infection and monitored for 22 weeks was very effective against the parasite. It resulted in a marked increase in survivorship of treated mice. Repetition of the dose regimen after a 10-day rest period was even more effective. However, survivorship of infected animals decreased with the delay of therapy. Early treatment (5 weeks post-infection) resulted in 100% survival compared to 13% only for untreated animals. If therapy was instituted at 8 weeks post-infection, only 70% of the treated mice survived. Treated animals appeared healthy and were found to have less splenomegaly and hepatomegaly. Combination therapy also caused a significant reduction in the number of worms as well as the number of eggs in the liver and small intestine. However, these differences diminished as the treatment was delayed. The number of eggs in the liver was reduced from an average of 120,000 eggs per liver in untreated animals to approximately 16,000 eggs per liver when treated at 5 weeks post-infection. When treatment was delayed to 8 weeks post infection, the reduction in liver egg count was not as dramatic (88,000 eggs per liver). Similarly, the number of eggs was reduced in the intestine from 1,759 to an average of 58 and 860 eggs per cm2 of the intestine when the mice were treated at 5 and 8 weeks post-infection respectively. However, some worms survived and resumed egg production after an extended period of recuperation. Histological examination indicated that combination therapy was effective in preventing the formation of new egg granulomas but not on pre-existing granulomas. PMID- 1900160 TI - "Nurse, don't bother me". PMID- 1900161 TI - Antiproliferative effects of cytokines on squamous cell carcinoma. AB - A panel of 12 squamous cell carcinoma of the head and neck (SCCHN) cell lines has been used to determine sensitivity of tumor cells to cytokines, tumor necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma), and interferon alfa (IFN alpha) in vitro. Antiproliferative activity of these cytokines on squamous cell carcinoma of the head and neck monolayers was measured in a colorimetric MTT [3 (4,5-dimethylthiazol-2yl)-2,5-diphenyl tetrazolium bromide]-based assay. All 12 cell lines tested were sensitive to IFN-gamma, with the 50% inhibitory dose (ID50) ranging from 0.07 +/- 0.001 to 104 +/- 4.6 U/mL. The TNF-alpha showed antiproliferative activity on three cell lines at relatively high doses (ID50 from 55 +/- 4.1 to 847.10 +/- 10 U/mL), and IFN-alpha was growth inhibitory in only one line (ID50 = 1211 +/- 46.2 U/mL). The combination of IFN-gamma and TNF alpha had a synergistic antiproliferative effect on eight cell lines and an additive effect on two cell lines. In two cell lines, the effect of the combination was equal to that of IFN-gamma alone. A combination of IFN-alpha and TNF-alpha resulted in cell growth inhibition in six of the seven lines tested, and this effect was synergistic. These in vitro studies indicate that combinations of IFN-gamma and TNF-alpha or IFN-alpha and TNF-alpha may be more growth inhibitory against squamous cell carcinoma of the head and neck and at lower doses than each of these cytokines used singly. PMID- 1900163 TI - Transforming the UKCC. PMID- 1900162 TI - Flexi-time? PMID- 1900164 TI - National Boards lose control of funding. PMID- 1900165 TI - Accident, negligence or crime? PMID- 1900166 TI - Nutrition and the healthy adult. AB - Great public concern over the constituents of diets, encouraged by widely publicised and often conflicting advice on what constitutes 'healthy' and 'unhealthy' items, is placing pressures on nurses to understand the nutritional make-up of foods and their uses and abuses. Anne Halliday takes a general look at the requirements of the healthy adult and suggests that there is a need for individuals to review the nature of their whole diet, not merely one or two constituents of it. Nurses will find her article invaluable from a personal as well as professional perspective. PMID- 1900167 TI - Issues in community care services. AB - In the first part of this series on issues in ward management facing charge nurses, Helen Evers addresses the problem of communication between hospital and community on patient discharges. Recent years have seen the development of liaison and co-ordinator posts whose incumbents aim to facilitate planned and organised discharge procedures, but the appointment of such personnel may not provide a complete answer to the problem. The ultimate arbiter of effective transition from hospital to home is more likely to be the quality of communication between charge and district nurse. PMID- 1900168 TI - The bare bones of reform. PMID- 1900169 TI - The management of cystic fibrosis. AB - Cystic fibrosis is a chronic, life-threatening inherited disease which poses severe physical, psychological and social problems for the sufferer and his or her family. Frances Duncan-Skingle and Fiona Foster present an overview of recent developments in the clinical management of this distressing condition. PMID- 1900170 TI - Stress and its management. AB - Despite significant evidence of the harmful effects of stress in individuals and the subsequent cost in terms of human suffering and lost production due to sickness leave, management may still apply covert sanctions against people who have the 'courage' to admit to their stress. Distancing herself from such attitudes, Caroline Hiscox describes the results of her staff survey which demonstrates an over-whelming endorsement of the need for support groups to help health care workers cope with the stressors they encounter in their professional and domestic situations. PMID- 1900171 TI - Points of view. PMID- 1900172 TI - G force? PMID- 1900174 TI - Profile: in pursuit of youth. Interview by Jean Gray. PMID- 1900173 TI - Community care. Earning difficulties. PMID- 1900175 TI - Receiving and caring for a burned patient. PMID- 1900176 TI - A healthy occupation? PMID- 1900177 TI - Occupational health nursing. A strategy for management. PMID- 1900178 TI - Occupational health nursing. A handbook for health. PMID- 1900179 TI - The Clay column. PMID- 1900180 TI - Fighting for care in the community. Interview by Norah Casey. PMID- 1900181 TI - Scottish excellence. Linking-up for quality. PMID- 1900182 TI - Stress management in dermatology patients. AB - The association of skin disorder with emotion has been recognised for some time. Maureen Marshall explores the use of stress management techniques such as relaxation, aromatherapy and therapeutic massage as a means of helping patients with dermatological conditions to cope with the pressures which may exacerbate their skin problems. Nurses, working in tandem with psychologists, have a key role to play in patients' emotional care, but greater commitment in terms of training and funding are required to prepare properly them for this function. PMID- 1900184 TI - Co-operative learning opportunities. AB - Government initiatives which encourage joint ventures between the public and independent health-care sectors offer opportunities for the development of student and trained nurse educational curricula. Peter Dunham outlines the proposals initiated by East Surrey Health Authority and BUPA Gatwick Park Hospital to facilitate quality learning experiences for the nurses of both authorities. The measures, he believes, open the door to future developments. PMID- 1900183 TI - The thin end of the wedge? PMID- 1900185 TI - Abortifacient drugs: ethico-legal issues. AB - It is conceivable that an oral medicine capable of terminating pregnancy will become available for use in this country. Such a drug will pose significant moral and legal dilemmas for nurses who may find themselves embroiled in situations where they are uncertain of how to reconcile their consciences with statutory law and the requirements of their employers. The RCN Ethics and Nursing Committee offer some guidance on how nurses should act under such difficult circumstances. PMID- 1900186 TI - Preparing health care assistants. AB - In the fourth part of this series on issues in ward management facing charge nurses, Sheila Mackie Bailey looks at the charge nurse's role in preparing and educating the health care assistant or support worker. The imminent adjustment of student nurses' clinical status makes the development of a skilled and educated assistant for the trained nurse an urgent necessity. Of all those involved in defining and delimiting this role, the charge nurse assumes the key responsibility, but it is a responsibility which requires proper preparation and support before it can be adequately exercised. PMID- 1900187 TI - Points of view. PMID- 1900188 TI - Who's to blame? PMID- 1900189 TI - Primary teamwork. PMID- 1900190 TI - Difficulties with research. PMID- 1900191 TI - Oxidation of beta-very low density lipoprotein by endothelial cells enhances its metabolism by smooth muscle cells in culture. AB - We have previously shown that beta-very low density lipoprotein (beta-VLDL) incubated with bovine aortic endothelial cells (ECs) is bound and internalized more readily by cultured rabbit aortic smooth muscle cells (SMCs) than is beta VLDL incubated in the absence of ECs, resulting in enhanced accumulation of cholesterol. To investigate the mechanism by which this occurs, beta-VLDL from hypercholesterolemic rabbit serum was incubated with cultured bovine aortic ECs. This resulted in the formation of thiobarbituric acid (TBA)-reactive material indicating extensive lipid peroxidation. The formation of TBA-reactive material, the increased metabolism of beta-VLDL by rabbit aortic SMCs, and the increased accumulation of cholesterol were prevented by superoxide dismutase, EDTA, several antioxidants, and, to a lesser extent, by 5,8,11,14-eicosatetraynoic acid, but not by acetylsalicylic acid, suggesting that potential oxidizing agents were the superoxide anion, metal ions, and lipoxygenase derivatives, but not cyclooxygenase derivatives. The percentage composition of phospholipid, protein, triglyceride, and free and esterified cholesterol of EC-modified beta-VLDL did not differ significantly from the unmodified lipoprotein. Displacement studies showed that only part of the interaction of both EC-beta-VLDL and unmodified beta VLDL occurred through the B/E receptor and that the EC-beta-VLDL displaced 125I beta-VLDL to a greater extent than did unmodified beta-VLDL. This indicated that the EC-beta-VLDL interacted more strongly with receptors on SMCs. PMID- 1900192 TI - Hepatic lipase promotes a loss of apolipoprotein A-I from triglyceride-enriched human high density lipoproteins during incubation in vitro. AB - Studies have been performed to investigate a possible mechanism to account for the low concentrations of apolipoproteins A-I (apo A-I) in subjects with hypertriglyceridemia. Incubation of human plasma in vitro with canine hepatic lipase resulted in the hydrolysis of approximately half the triglyceride in the high density lipoproteins (HDLs), but little change in the concentrations of other HDL constituents. However, when the plasma was supplemented with cholesteryl ester transfer protein and very low density lipoproteins to enrich the HDL with triglyceride, hepatic lipase promoted not only a significant reduction in HDL triglyceride acquired by the lipid transfer process but also an enhanced transfer of cholesteryl esters out of the particles. These changes were accompanied by a marked loss of apo A-I from HDL, which was demonstrated independently by ultracentrifugation, size-exclusion chromatography, and gradient gel-immunoblot analysis. The apo A-I lost from HDL was recovered in the "lipoprotein-free" fraction of plasma. The results of these studies indicate that primary reductions in the concentration of HDL core lipids in vitro are accompanied by a secondary loss of apo A-I from HDL. While recognizing the need for caution in any extrapolation from observations made in vitro to what may occur in vivo, these studies are nevertheless consistent with a proposition that the low concentration of apo A-I in subjects with hypertriglyceridemia is secondary to the reduced concentration of HDL core lipids in such subjects. PMID- 1900193 TI - Toxicity of oxygenated cholesterol derivatives toward cultured human umbilical vein endothelial cells. AB - Human umbilical vein endothelial cells were cultured in the presence of several oxygenated cholesterol derivatives that are known to affect the viability of other cell lines. 5-Cholestene-3 beta,7 beta-diol (7 beta-hydroxycholesterol) caused a time- and concentration-dependent perturbation of the endothelial cells. Exposure to 50 mumol/l of this compound for 18 hours resulted in marked contraction of the cells, followed by increasing cell detachment from the substrate and Trypan Blue uptake in detached cells. Concomitantly release of lactate dehydrogenase from the cells reached about 80% at 24 hours. The release of tissue plasminogen activator and tissue plasminogen activator inhibitor-1 antigens decreased at a concentration of 7 beta-hydroxycholesterol lower than that required for reducing general protein synthesis. 7 beta-Hydroxycholesterol at 50 mumol/l first increased the release and then (at 100 mumol/l) inhibited the synthesis of von Willebrand factor. Incubation with 100 mumol/l of 5-cholestene-3 beta, 7 alpha,22(R)-triol (7 alpha,22-dihydroxycholesterol)e and the isomeric 5 cholestene-3 beta, 7 beta, 22(R)-triol (7 beta, 22-dihydroxycholesterol) caused formation of intercellular gaps and some detachment of the cells after 24 hours. Cell injury was slightly more pronounced for the 7 alpha, 22-dihydroxycholesterol than for the 7 beta-isomer. Incubations with cholesterol under the same conditions gave no sign of cell injury. PMID- 1900194 TI - Relationship between mitochondrial NADH-ubiquinone reductase and a bacterial NAD reducing hydrogenase. AB - Bovine mitochondrial NADH-ubiquinone reductase (complex I), the first enzyme in the electron-transport chain, is a membrane-bound assembly of more than 30 different proteins, and the flavoprotein (FP) fraction, a water-soluble assembly of the 51-, 24-, and 10-kDa subunits, retains some of the catalytic properties of the enzyme. The 51-kDa subunit binds the substrate NAD(H) and probably contains both the cofactor, FMN, and also a tetranuclear iron-sulfur center, while a binuclear iron-sulfur center is located in the 24- or 10-kDa proteins. The 75-kDa subunit is the largest of the six proteins in the iron-sulfur protein (IP) fraction, and its sequence indicates that it too contains iron-sulfur clusters. Partial protein sequences have been determined at the N-terminus and at internal sites in the 51-kDa subunit, and the corresponding cDNA encoding a precursor of the protein has been isolated by using a novel strategy based on the polymerase chain reaction. The mature protein is 444 amino acids long. Its sequence, and those of the 24- and 75-kDa subunits, shows that mitochondrial complex I is related to a soluble NAD-reducing hydrogenase from the facultative chemolithotroph Alcaligenes eutrophus H16. This enzyme has four subunits, alpha, beta, gamma, and delta, and the alpha gamma dimer is an NADH oxidoreductase that contains FMN. The gamma-subunit is related to residues 1-240 of the 75-kDa subunit of complex I, and the alpha-subunit sequence is a fusion of homologues of the 24- and 51-kDa subunits, in the order N- to C-terminal. The most highly conserved regions are in the 51-kDa subunit and probably form parts of nucleotide binding sites for NAD(H) and FMN. Another conserved region surrounds the sequence motif CysXXCysXXCys, which is likely to provide three of the four ligands of a 4Fe-4S center, possibly that known as N-3. Characteristic ligands for a second 4Fe-4S center are conserved in the 75-kDa and gamma-subunits. This relationship with the bacterial enzyme implies that the 24- and 51-kDa subunits, together with part of the 75-kDa subunit, constitute a structural unit in mitochondrial complex I that is concerned with the first steps of electron transport. PMID- 1900195 TI - cDNA cloning of porcine brain prolyl endopeptidase and identification of the active-site seryl residue. AB - Prolyl endopeptidase is a cytoplasmic serine protease. The enzyme was purified from porcine kidney, and oligonucleotides based on peptide sequences from this protein were used to isolate a cDNA clone from a porcine brain library. This clone contained the complete coding sequence of prolyl endopeptidase and encoded a polypeptide with a molecular mass of 80,751 Da. The deduced amino acid sequence of prolyl endopeptidase showed no sequence homology with other known serine proteases. [3H]Diisopropyl fluorophosphate was used to identify the active-site serine of prolyl endopeptidase. One labeled peptide was isolated and sequenced. The sequence surrounding the active-site serine was Asn-Gly-Gly-Ser-Asn-Gly-Gly. This sequence is different from the active-site sequences of other known serine proteases. This difference and the lack of overall homology with the known families of serine proteases suggest that prolyl endopeptidase represents a new type of serine protease. PMID- 1900196 TI - Human platelet P-235, a talin-like actin binding protein, binds selectively to mixed lipid bilayers. AB - The interaction of platelet talin (P-235) with mixtures of dimyristoylphosphatidylcholine (DMPC), dimyristoylphosphatidylglycerol (DMPG) and dimyristoylphosphatidylserine (DMPS) as well as with pure lipids was studied in reconstituted lipid bilayers. Incorporation of platelet talin into vesicles was achieved by self-assembly during cycles of freeze-thawing of co-dispersions containing vesicles and the purified protein. The yield of protein incorporation as a function of lipid composition was determined by measuring the protein/lipid ratio using protein assay, phosphate determination and gel electrophoresis in parallel. Protein-lipid interactions are monitored by high sensitive differential scanning calorimetry (DSC) measuring (i) the shifts of transition states delta Ts* and delta Tl*, where Ts represents the solidus line, the onset of lipid chain melting, and Tl the liquidus line, the endpoint of chain melting, and (ii) the heats of transition. Cytoplasmic talin differs from a membrane bound form by its ability and mode of lipid interaction. The latter partially penetrates into the hydrophobic region of the bilayer, which renders a low incorporation rate even into neutral lipids. This interaction is greatly enhanced in the presence of charged lipids: a marked shift of Tl occurs due to a selective electrostatic interaction of the protein with the membrane surface. Evidence for a selective binding is also provided by Fourier transform infrared spectroscopy (FTIR). Right side-out oriented platelet talin can be cleaved by proteinases, which truncate the extrinsic electrostatic binding domain but not the hydrophobic. In addition, reconstituted platelet talin, like in vivo, can be cleaved by thrombin. The interaction of cytoplasmic platelet talin with lipid bilayers is purely electrostatic. Our data suggest that protein reconstitution by freeze-thawing is an equilibrium process and that the protein distribution between the membrane and water is determined by the Nernst distribution law. Consequently, the work of protein transfer from water into the bilayer can be measured as a function of charged lipids. PMID- 1900198 TI - Purification and characterisation of a beta-glucosidase (cellobiase) from a mushroom Termitomyces clypeatus. AB - A beta-glucosidase with cellobiase activity was purified to homogeneity from the culture filtrate of the mushroom Termtomyces clypeatus. The enzyme had optimum activity at pH 5.0 and temperature 65 degrees C and was stable up to 60 degrees C and within pH 2-10. Among the substrates tested, p-nitrophenyl-beta-D glucopyranoside and cellobiose were hydrolysed best by the enzyme. Km and Vm values for these substrates were 0.5, 1.25 mM and 95, 91 mumol/min per mg, respectively. The enzyme had low activity towards gentiobiose, salicin and beta methyl-D-glucoside. Glucose and cellobiose inhibited the beta-D-glucosidase (PNPGase) activity competitively with Ki of 1.7 and 1.9 mM, respectively. Molecular mass of the native enzyme was approximated to be 450 kDa by HPLC, whereas sodium dodecyl sulphate polyacrylamide gel electrophoresis indicated a molecular mass of 110 kDa. The high molecular weight enzyme protein was present both intracellularly and extracellularly from the very early growth phase. The enzyme had a pI of 4.5 and appeared to be a glycoprotein. PMID- 1900197 TI - C-reactive protein in eel: purification and agglutinating activity. AB - C-reactive protein was highly purified from Japanese eel (Anguilla japonica) serum by precipitation with phosphatidyl-choline and Ca2+. On SDS-PAGE, eel C reactive protein (eCRP) migrated as a single band with a molecular weight of 24,000 under reducing and 23,500 under non-reducing conditions. The molecular weight of native eCRP was estimated to be 120,000 by Sephacryl S-300 gel filtration. The eCRP was detected within the albumin region on immunoelectrophoresis. The eCRP showed an agglutinating activity against Streptococcus pneumoniae in the presence of Ca2+, and the activity was inhibited by 1 mM EDTA or 1 mM phosphorylcholine (PC). The eCRP also agglutinated rabbit red blood cells (RRBC), but not human and five other kinds of red blood cell. The hemagglutinating activity was inhibited by glucosamine or mannose. The eCRP formed a precipitin line with histone, protamine, poly(L-lysine) and poly(L arginine) in agarose gel. The serum levels of eCRP were distributed in 6.8 ng/ml 5.3 mg/ml, n = 187, the mean value being 834 ng/ml. PMID- 1900199 TI - Location of lysine-129 and lysine-40/41 with respect to retinylidene chromophore in bacteriorhodopsin. AB - Fluorescence properties of fluorescamine-modified bacteriorhodopsin (BR) have been studied. BR reacts with fluorescamine (1:2 ratio) to give protein (FLBR-I) modified at Lys-129. By making use of citraconic anhydride as a masking reagent, fluorescamine modification of Lys-40/41 in BR has been achieved. Forster's resonance energy transfer studies indicate that the distance between FL-Lys-129 and retinylidene chromophore is 11 A, whereas that between FL-Lys-40/41 and retinylidene chromophore is 24 A. These measured distances have been analysed in terms of BR structure. PMID- 1900200 TI - Enzymic synthesis of steroid sulphates. XVII. On the structure of bovine estrogen sulphotransferase. AB - Estrogen sulphotransferase plays a major role in controlling intracellular levels of 17 beta-estradiol in human mammary cancer cells and human endometrium. Bovine estrogen sulphotransferase c-DNA has recently been cloned; the encoded protein having a maximum Mr of 35,000 (Nash, A.R. et al. (1988) Aust. J. Biol. Sci. 41, 507-516). Enzyme of Mr 35,000 by SDS-PAGE has now been isolated and cyanogen bromide-cleaved peptides sequenced. The latter were identified in the c-DNA predicted amino acid sequence which confirms that the active enzyme (Mr approximately 70,000) exists as a dimer of identical subunits. Sequence data on similar peptides isolated from an enzyme preparation containing a protein of Mr 74,000 as the major species on SDS-PAGE, which was previously thought to represent the enzyme, suggested that this protein was transferrin. This was confirmed by PAGE, SDS-PAGE, susceptibility to neuraminidase and reaction with bovine transferrin antibody. Isoelectric focusing experiments show that active enzyme exists in two or three polymorphic forms (pI values 5.3, 5.7 and possibly 5.9) having similar physicochemical properties of polymorphic forms of transferrin so that they overlap on ion-exchange chromatography and PAGE. The enzyme shows some homology to the amino acid sequence close to the Fe-binding site in lactoferrin and the question is raised as to the possible presence of a tightly bound metal in estrogen sulphotransferase involved in the binding of adenosine 3'-phosphate 5'-phosphosulphate. PMID- 1900201 TI - Glucose dehydrogenase from Bacillus subtilis expressed in Escherichia coli. I: Purification, characterization and comparison with glucose dehydrogenase from Bacillus megaterium. AB - Escherichia coli containing the Bacillus subtilis glucose dehydrogenase gene on a plasmid (prL7) was used to produce the enzyme in high quantities. Gluc-DH-S was purified from the cell extract by (NH4)2SO4-precipitation, ion-exchange chromatography and Triazine-dye chromatography to a specific activity of 375 U/mg. The enzyme was apparently homogenous on SDS-PAGE with a subunit molecular mass of 31.5 kDa. Investigation of Gluc-DH-S was performed for comparison with the corresponding properties of Gluc-DH-M. The limiting Michaelis constant at pH 8.0 for NAD+ is Ka = 0.11 mM and for D-glucose Kb = 8.7 mM. The dissociation constant for NAD+ is Kia = 17.1 mM. Similar to Gluc-DH-M, Gluc-DH-S is inactivated by dissociation under weak alkaline conditions at pH 9.0. Complete reactivation is attained by readjustment to pH 6.5. Ultraviolet absorption, fluorescence and CD-spectra of native Gluc-DH-S, as well as fluorescence- and CD backbone-spectra of the dissociated enzyme were nearly identical to the corresponding spectra of Gluc-DH-M. The aromatic CD-spectrum of dissociated Gluc DH-S was different, representing a residual ellipticity of tryptophyl moieties in the 290-310 nm region. Density gradient centrifugation proved that this behaviour is due to the formation of inactive dimers in equilibrium with monomers after dissociation. In comparison to Gluc-DH-M, the kinetics of inactivation as well as the time-dependent change of fluorescence intensity at pH 9.0 of Gluc-DH-S showed a higher velocity and a changed course of the dissociation process. PMID- 1900202 TI - Sulphate activates phosphorylase b by binding to the Ser (P) site. AB - The notion, in a recent crystallographic study on the R state phosphorylase b (Barford, D. and Johnson, L.N. (1989) Nature 340, 609-616), that sulphate ions activate the enzyme by interacting within 2 A of the phosphorylatable Ser-14, is directly supported by kinetic studies on phosphorylase b', a proteolytic species which lacks the N-terminal 16 residues. The results show that this form of the enzyme is no longer activated by ammonium sulphate. PMID- 1900203 TI - On the mechanistic reasons for the dual positional specificity of the reticulocyte lipoxygenase. AB - A set of octadecadienoic acid isomers and selected eicosatrienoic acids were tested as substrates for the lipoxygenases from soybeans and reticulocytes. Among the dienoic fatty acids, 8Z,11Z-octadecadienoic acid containing a n - 9 doubly allylic methylene group turned out to be the best substrate for the reticulocyte enzyme. This substrate was converted to its corresponding n - 7 hydroperoxy derivative. The soybean lipoxygenase, in contrast, prefers the 9Z,12Z octadecadienoic acid (linoleic acid) which is oxygenated to its n - 6 hydroperoxy derivative. In both cases a strong preference for the LS-isomer has been observed. Analysis of the oxygenation products formed from various eicosatrienoic acids indicated that 8Z,11Z,14Z-eicosatrienoic acid was converted by the reticulocyte enzyme to its 12S- and 15S-hydroperoxy derivative in a ratio of about 1:7 (dual positional specificity), whereas the 7Z,10Z,13Z-isomer was oxygenated predominantly (greater than 97%) to its 14S-hydroperoxy derivative (singular positional specificity). 9Z,12Z,15Z-eicosatrienoic acid was oxygenated with a dual positional specificity to the corresponding 13- and 16-hydroperoxy compounds in a ratio of about 7:1. The soybean lipoxygenase converts the 8Z,11Z,14Z-isomer with a singular positional specificity to the corresponding 15S hydroperoxy derivatives. The 9Z,12Z,15Z-eicosatrienoic acid, however, was oxygenated with a dual positional specificity to its 13S-hydroperoxy and 16S hydroperoxy derivative in a ratio of about 1:4. PMID- 1900204 TI - 12-Lipoxygenase from rat basophilic leukemia cells: separation from 5 lipoxygenase and temperature-dependent inactivation by hydroperoxy fatty acid. AB - 12-Lipoxygenase and 5-lipoxygenase from rat basophilic leukemia cells were separated by protein-HPLC in a single step. Upon incubation in the presence of Ca2+, 12-lipoxygenase converted arachidonic acid into 12(S) hydroxyeicosatetraenoic acid and linoleic acid into 13(S) hydro(pero)xyoctadecadienoic acid. The reaction products were analyzed by reversed-phase and chiral straight-phase HPLC with ultraviolet-detection. Using the cytosolic fraction of rat basophilic leukemia cells, optimal 12-lipoxygenase activity was observed at 10 degrees C. At 37 degrees C 12-lipoxygenase was very rapidly inactivated by its own product, hydroperoxy fatty acid, at low concentrations (10-100 nM). PMID- 1900205 TI - Inhibition of arachidonic acid incorporation into erythrocyte phospholipids by peracetic acid and other peroxides. Role of arachidonoyl-CoA: 1-palmitoyl-sn glycero-3-phosphocholine acyl transferase. AB - To explore possible mechanisms of the arachidonic acid deficiency of the red blood cell membrane in alcoholics, we compared the effect of ethanol and its oxidized products, acetaldehyde and peracetic acid, with other peroxides on the accumulation of [14C]arachidonate into RBC membrane lipids in vitro. Incubation of erythrocytes with 50 mM ethanol or 3 mM acetaldehyde had no effect on arachidonate incorporation. Pretreatment of erythrocytes with 10 mM hydrogen peroxide, 0.1 mM cumene hydroperoxide or 0.1 mM t-butyl hydroperoxide had little effect on [14C]arachidonate incorporation in the absence of azide. However, pretreatment of cells with N-ethylmaleimide, 0.1 mM peracetic acid or performic acid, with or without azide, inhibited arachidonate incorporation into phospholipids but not neutral lipids. In chase experiments, peracetate also inhibited transfer of arachidonate from neutral lipids to phospholipids. To investigate a possible site of this inhibition of arachidonate transfer into phospholipids by percarboxylic acids, we assayed a repair enzyme, arachidonoyl CoA: 1-palmitoyl-sn-glycero-3-phosphocholine acyl transferase (EC 2.3.1.23). As in intact cells, phospholipid biosynthesis was inhibited more by N-ethylmalemide and peracetic acid than by hydrogen peroxide, cumene hydroperoxide, and t-butyl hydroperoxide. Peracetic acid was the only active inhibitor among ethanol and its oxidized products studied and may deserve further examination in ethanol toxicity. PMID- 1900206 TI - Characterization of CoA-independent transacylase activity in U937 cells. AB - Coenzyme A-independent transacylase (CoA-IT) mediates the transfer of polyunsaturated fatty acids from the sn-2 position of a donor phospholipid to the sn-2 position of an acceptor lyso-phospholipid. We have characterized this activity in U937 cells, a human monocytic cell line. The microsomes of these cells contained CoA-IT activity which demonstrated a fatty acid preference for transferring arachidonic acid into exogenously added 1-alkyl-2-lyso-GPC. This enzymatic activity was optimum between pH 6.5 and 9, was heat labile and displayed an apparent Km for 1-alkyl-2-lyso-GPC of 0.4 microM. This activity was not dependent on Ca2+, Mg2+, CoA or ATP, was not inhibited by 2-mercaptoethanol nor by addition of product, 1-alkyl-2-acyl-GPC. The activity of this enzyme was not altered by differentiation of U937 cells towards the macrophage with Me2SO. Treatment of U937 cells with dexamethasone had no effect on transacylase activity. The activity of this enzyme was decreased by the serine esterase inhibitors phenylmethyl-sulfonyl fluoride and N-tosyl-L-phenylalanine chloromethyl ketone and by the histidine modifier diethyl pyrocarbonate, suggesting that CoA-IT may belong to a family of acyltransferase enzymes typified by LCAT. CoA-IT activity was not affected by compounds that affect PLA2 activity, such as quinacrine, aristolochic acid and arachidonic acid, suggesting a mechanism of action for CoA-IT different from classical, low molecular weight PLA2 enzymes. In conclusion, U937 cells contain CoA-IT activity and this study extends our previous knowledge of this enzyme by demonstrating the differences between CoA-IT and PLA2 enzymes and suggesting similarities between CoA-IT and LCAT. PMID- 1900207 TI - Investigation of the mechanism of biosynthesis of 8-hydroxyeicosatetraenoic acid in mouse skin. AB - One of the many changes induced by topical application of phorbol ester or calcium ionophore A23187 to mouse skin is the appearance of an enzymic activity which will convert arachidonic acid to its 8-hydroxyeicosatetraenoic acid metabolite (8-HETE) (Gschwendt, M., et al (1986) Carcinogenesis 7, 449-455). Induction of this activity is lower in strains of mice with a weak inflammatory response to TPA, and the 8-HETE may be involved in the inflammation or hyperplasia. To further characterize the activity, we first measured the chirality of the product; it is almost exclusively the 8DS)-hydroxy enantiomer (8S-HETE). The 8(S)-HETE is formed from octadeuterated arachidonic acid with complete retention of deuterium labels, indicating that a keto intermediate is not involved in the biosynthesis. Using arachidonic acids labeled with a prochiral tritium in either the 10DR or 10LS positions, we found that the biosynthesis of 8S-HETE is associated with the stereoselective abstraction of the 10DR hydrogen from the 10-carbon of the substrate. This stereoselective hydrogen removal conforms to the properties of an 8S-lipoxygenase. This is the only lipoxygenase known to catalyze solely 8S-oxygenation of arachidonic acid. The recent characterization of stereoselective biological effects for other HETEs serve as strong precedents to suggest that 8S-HETE has a specific role in the cellular tissue response to TPA. PMID- 1900208 TI - Educate the phagocyte! PMID- 1900209 TI - Protein status and metabolic expenditure determine the response to intravenous nutrition--a new classification of surgical malnutrition. AB - To determine whether nutritional and metabolic factors affect the response to intravenous nutrition (IVN) 146 surgical patients were classified according to their protein and metabolic status using direct measurements of body protein and metabolic expenditure. The patients were grouped into four categories: category I, moderate to severe protein depletion without raised metabolic expenditure; category II, moderate to severe protein depletion with raised metabolic expenditure; category III, mild protein depletion without raised metabolic expenditure; and category IV, mild protein depletion with raised metabolic expenditure. After 2 weeks of IVN patients in category I gained a mean(s.e.m.) of 0.43(0.06) kg of body protein (P less than 0.001) and had significant rises in both plasma transferrin and prealbumin (P less than 0.05); patients in category II gained 0.30(0.11) kg of protein (P less than 0.005) and also had significant rises in transferrin and prealbumin (P less than 0.05). Patients in category III lost 0.24(0.11) kg protein (P less than 0.05) and had no changes in either transferrin or prealbumin and patients in category IV lost 0.51(0.13) kg of body protein (P less than 0.001) and although there was a significant rise in plasma prealbumin there was no significant change in plasma transferrin. When postoperative patients were examined separately, they did not differ significantly from preoperative patients except in category I, where their protein gain was only 0.19(0.10) kg, an amount not significantly different from that gained by patients in category II. In each of the four categories described, the changes in total body protein occurring with 2 weeks of IVN were determined by the relative effects of two competing processes; protein depletion and raised metabolic expenditure. With moderate to severe protein depletion (approximately 30 per cent depletion of body protein stores) there was a marked tendency to gain protein with IVN. When the patient had a raised metabolic expenditure or was postoperative this tendency of depleted patients to gain protein was still present but it was less. With only mild protein depletion (approximately 10 per cent depletion) increases in metabolic expenditure made it difficult, if not impossible, to prevent continuing protein loss in spite of aggressive nutritional support. The patient categories we have described determine the response to IVN and form the basis of a new clinical classification of surgical malnutrition. PMID- 1900210 TI - Study of belching ability in antireflux surgery patients and normal volunteers. AB - The ability to belch was evaluated by a novel test, after gaseous stomach distension to standard volume, in 16 patients after antireflux surgery and nine healthy volunteers. A structured assessment of dyspeptic symptoms was also carried out in both groups. Repeat studies in volunteers showed acceptable reproducibility for the new test of belching capacity (within-subject coefficient of variance 4.5 per cent). After antireflux surgery, patients had lower volume individual belches (median(range) 27.5(0-104) ml in patients versus 76(15-165) ml in volunteers; P less than 0.02) and belched less gas within 1 h of the stimulus than volunteers (median(range) 205(0-1363) ml in patients versus 456(45-818) ml in volunteers; P less than 0.05). Belching frequency was similar in both groups. The incidence and severity of symptoms were unrelated to belched gas volumes. PMID- 1900211 TI - Localization of the primary auditory area in man. AB - The localization of the primary auditory cortex in man was studied by direct recordings in 150 different sites in the superior transverse gyrus, especially in Heschl's gyrus and the planum temporale. The distribution of the primary evoked responses (N13/P17/N26) was studied in 15 epileptic patients who were candidates for surgical treatment. Precise topography of recording sites was determined stereotactically. Our results provide evidence for considering only a restricted portion of Heschl's gyrus (its posteromedial part) as the primary auditory area. PMID- 1900212 TI - Predictors of chlamydial infection and gonorrhea among patients seen by private practitioners. AB - OBJECTIVE: To identify the predictors of chlamydial infection and gonorrhea among patients tested by general practitioners. DESIGN: Prospective study. SETTING: General private practice, family planning and abortion clinic, adolescent clinic, sexually transmitted disease (STD) clinic and community health clinic in downtown Montreal. PATIENTS: The 2856 patients were included because of symptoms compatible with an STD, a history of sexual contact with a person known or suspected to have chlamydial infection, a history of a nonexclusive sexual relationship or presentation for an abortion. MEASURES: Patient information was obtained by the attending physician on a standard form. Enzyme immunoassay (EIA) for Chlamydia trachomatis and culture for Neisseria gonorrhoeae were performed on cervical (female) or urethral (male) samples. Stepwise logistic regression was used to identify the predictors of infection. RESULTS: The EIA results were positive in 11.1% of the cases and the culture results in 2.3%. Among the males chlamydial infection was independently associated with low age (odds ratio [OR] = 0.88 per year), heterosexuality (OR = 4.99), urethral discharge (OR = 3.74) and the absence of a history of gonorrhea (OR = 0.51). Gonorrhea was associated with urethral discharge (OR = 24.3) and homosexuality (OR = 3.68). Among the females chlamydial infection was associated with low age (OR = 0.79 per year), a history of sexual contact with a person known to have chlamydial infection (OR = 2.30), multiple sexual partners in the previous 12 months (OR = 1.60) and a reason for the test other than screening purposes (OR = 0.60). Gonorrhea was associated with a reason other than screening (OR = 0.24) and low age (OR = 0.74 per year). Among the patients tested for screening purposes age was the only significant predictor of chlamydial infection (OR = 0.79 per year), and the prevalence of gonorrhea was 0.4%. The actual rate of chlamydial infection was 11.8% among the patients younger than 25 years, 5.7% among those 25 to 34 years and 0.6% among those over 34. CONCLUSIONS: Age alone can be used as a criterion to screen for chlamydial infection among asymptomatic patients without a history of sexual contact with a person known or suspected to have such infection and with a history of a nonexclusive relationship. The prevalence in our population justifies screening people up to 34 years of age. PMID- 1900214 TI - A mammary cancer suppressor gene and its site of action in the rat. AB - Fifty-day-old female rats of the inbred Osborne-Mendel (OM) and Copenhagen (COP) strains were exposed to a single dose of either of 2 highly effective mammary chemical carcinogens, 7,12-dimethylbenz[a] anthracene (DMBA) or 1-methyl-1 nitrosourea (MNU). Female OM rats are highly susceptible to both of these carcinogens developing greater than 5 mammary adenocarcinomas per rat following a single exposure to either chemical. In contrast, female COP rats are completely resistant to both DMBA and MNU mammary cancer induction. Genetic breeding analysis of the F1 and F2 hybrids produced by crossing COP to OM rats demonstrated that the resistance of the female COP rat to DMBA and MNU is due to the presence of a single dominant autosomal allele in the germ line of the COP rat. Transplantation experiments demonstrated that the site of action of this COP gene is within the mammary epithelial cells themselves, not systemically or at the local mammary gland level within nonepithelial mammary cells. The resistance to DMBA-induced mammary carcinogenesis affected by the COP gene does not involve prevention of the initial interaction of DMBA with the mammary epithelial cells, but suppression of the progression of these initiated mammary cells to full cancer. This suppression does not involve paracrine release of diffusible factor(s). This gene does not suppress the development of MNU-induced renal or bladder cancers in the COP female rats. Thus, this newly identified autosomal dominant gene is specifically a mammary cancer suppressor gene. Analysis of the response of female feral rats to DMBA or MNU exposure demonstrates that this mammary cancer suppressor gene is also functional in feral rats. This suggests that this mammary cancer gene is functionally inactivated either by mutation or deletion in the germ line of highly susceptible strains of rats like the OM and inbred Sprague-Dawley rats, but functionally retained in resistant strains like the COP. PMID- 1900213 TI - Inhibition of poly(adenosine diphosphate-ribose) polymerase by thymidine and thymidine analogues in L1210 cells and its relationship to the potentiation of the antitumor activity of 1,3-bis(2-chloroethyl)-1-nitrosourea but not of 3'-[3 (2-chloroethyl)-3-nitrosoureido]-3'-deoxythymidine. AB - The coadministration of thymidine (dThd) with either 1,3-bis(2-chloroethyl)-1 nitrosourea (BCNU) or 3'-[3-(2-chloroethyl)-3-nitrosoureido]-3'-deoxythymidine (3'-CTNU) to L1210-bearing mice significantly enhanced the antitumor activity of both nitrosoureas (T-S. Lin and W. H. Prusoff, Cancer Res., 47:394-397, 1987, and T-S. Lin, P.H. Fischer, J. C. Marsh, and W. H. Prusoff, Cancer Res., 42:1624 1629, 1982). As a possible mechanism for this observed enhancement, we have investigated the role of dThd as an inhibitor of poly(ADP-ribose) polymerase (ADPRP), an enzyme which is activated in response to DNA damage. Exposure of L1210 cells in culture to 50 microM BCNU resulted in a greater than 10-fold increase in ADPRP activity within 3-4 h. The polymerase activity increased with increasing BCNU concentration after a 4-h exposure, reaching apparent saturation at 50 microM BCNU. However, this activation was abolished by 2 mM dThd. Median inhibition of the ADPRP activity elicited by 30 and 75 microM BCNU occurred at 38 and 135 microM dThd, respectively. When BCNU was replaced by 3'-CTNU, no activation of ADPRP was observed, even at or above concentration of 3'-CTNU previously shown to cause DNA damage. 3'-Amino-3'-deoxythymidine, the principal hydrolysis product of 3'-CTNU, was found to be an inhibitor of BCNU-stimulated ADPRP activity with potency similar to dThd. Furthermore, intact 3'-CTNU was found to inhibit BCNU-stimulated ADPRP activity. Although 3'-CTNU should be capable of activating ADPRP by causing DNA damage, our results suggest that no net activation is observed due to inhibition by the various thymidine species present. Thus, inhibition of ADPRP by dThd following DNA damage by BCNU is consistent with the potentiation of antitumor activity previously reported. However, the observed potentiation of 3'-CTNU activity by dThd does not appear to result from such a mechanism. PMID- 1900215 TI - Fjord- and bay-region diol-epoxides investigated for stability, SOS induction in Escherichia coli, and mutagenicity in Salmonella typhimurium and mammalian cells. AB - The fjord-region diol-epoxides of benzo(c)phenanthrene combine high mutagenic and carcinogenic activity with low chemical reactivity. To study whether this is a unique property of these compounds or a more general characteristic of fjord region diol-epoxides, we have synthesized the anti- and syn-diastereomers of r 9,t-10-dihydroxy-11,12-oxy-9,10,11,12-tetrahydrobenzo(c)chrysene and r-11-t-12 dihydroxy-13,14-oxy-11,12,13,14-tetrahydrobenzo(g)chrysene. These compounds as well as the anti- and syn-diastereomers of the fjord-region diol-epoxides of benzo(c)phenanthrene and of the bay-region diol-epoxides of phenanthrene, chrysene, and benzo(a)pyrene were investigated for their half-lives in a physiological buffer, for their mutagenicity in Salmonella typhimurium (reversion of the his- strains TA97, TA98, TA100, and TA104), for induction of SOS response in Escherichia coli (SOS chromotest in strain PQ37) and for their mutagenicity in V79 Chinese hamster cells (acquisition of resistance to 6-thioguanine). All six of the investigated fjord-region diol-epoxides were more stable in physiological buffer at 37 degrees C (t1/2 greater than 2 h) than the six bay-region diol epoxides (t1/2 = 0.011 to 1.2 h). The half-lives correlated negatively with the calculated delta Edeloc values for the formation of the benzylic carbocations, and were consistently shorter for the syn- than for the corresponding anti diastereomer. All fjord-region diol-epoxides showed extraordinarily high activity in all six genotoxicity assays used. In mammalian cells, the anti-diol-epoxide of benzo(c)chrysene was 8.6 and 12 times more active than the anti-diol-epoxides of benzo(c)phenanthrene and benzo(a)pyrene, respectively, which were the most potent mutagens among the reference compounds. The other three newly available fjord region diol-epoxides were also markedly more mutagenic in mammalian cells than the reference compounds. Whereas the syn-diastereomers of the simple bay-region diolepoxides were clearly less mutagenic in mammalian cells than the corresponding anti-diastereomers, the differences in potency between diastereomers were small for the fjord-region diol-epoxides. In conclusion, the diol-epoxides of benzo(c)phenanthrene are not unique in their high biological activities. The two newly available diastereomeric pairs of fjord-region diol epoxides of benzo(g)- and benzo(c)chrysene proved to be even more active. For one of them, the diol-epoxides of benzo(g)chrysene, the delta Edeloc value for the formation of the benzylic carbocation is lower than for the benzo(c)phenanthrene diol-epoxides, for the other it is higher. PMID- 1900216 TI - Quantitation of aflatoxin B1-DNA adducts in woodchuck hepatocytes and rat liver tissue by indirect immunofluorescence analysis. AB - A quantitative indirect immunofluorescence technique was developed utilizing a monoclonal antibody (6A10) recognizing the imidazole ring-opened form of the major N-7 guanine adduct of aflatoxin B1 (AFB1). This method was used to investigate adduct formation in woodchuck hepatocytes treated in culture and in liver tissue of rats treated i.p. with AFB1. Fluorescein isothiocyanate-labeled secondary antiserum was used for adduct localization in conjunction with 4',6 diamidino-2-phenylindole dihydrochloride staining to localize nuclei. Quantitation of AFB1-DNA adducts was carried out by densitometric analysis of photographic slides. Specific nuclear staining was observed in both woodchuck hepatocytes and rat liver tissue. There was a dose-response relationship between fluorescence intensity and AFB1 dose in treated animals. Turnover of adducts could also be followed in animals over 48 h with this method. DNA was isolated from liver tissue of treated animals and adduct levels were quantitated by competitive enzyme-linked immunosorbent assay with antibody 6A10 and by fluorescence spectroscopy. There was a significant correlation of the quantitative immunofluorescence intensity with levels of AFB1 adducts detected by enzyme-linked immunosorbent assay (r = 0.61, P less than 0.05) and spectrofluorescence (r = 0.78, P less than 0.01). This immunohistochemical method should be applicable to the detection of adducts in liver tissues of humans exposed to high levels of dietary AFB1. PMID- 1900218 TI - [Nursing care of critical surgical patients with enteral nutritional support]. PMID- 1900219 TI - [Postoperative care of pancreatitis gravis with jejunal alimentation]. PMID- 1900217 TI - No inhibition of interferon gamma release in human lymphocytes by Ciamexone. AB - In previous experiments Ciamexone, derivative of 2-cyan-aziridine, was able to influence T-cell-mediated regulatory mechanisms but seemed to have no or only little effect on T cell effector mechanisms. On the basis of these observations Ciamexone seems to be a highly selective immunosuppressive agent. In order to evaluate further possible mechanisms of Ciamexone it was the aim of our investigation to study its influence on interferon gamma (IFN gamma) production in phytohaemogglutinin (PHA)-stimulated T lymphocytes of 15 tumour patients and 12 healthy reference subjects. The IFN gamma concentration of the cell supernatant was measured using an enzyme-linked immunosorbent assay. When the cells were stimulated with PHA at 7.5 micrograms/ml the IFN gamma concentration rose to significantly different values in the reference group (1.0 ng/ml) as compared to the tumour patients (0.4 ng/ml) (P less than 0.05). An addition of Ciamexone (at any of the concentrations administered) to PHA stimulation of peripheral blood mononuclear cells (PBMC) showed no influence on the IFN gamma release in either test group. The influence of hydrocortisone on the stimulation of PBMC with PHA resulted in a dose-dependent suppression of IFN gamma production in both test groups, again with significant differences between them. The IFN gamma concentration was 0.95 ng/ml in the reference group and 0.2 ng/ml in the tumour patients when 0.01 micrograms/ml hydrocortisone was added (P less than 0.05). At 10 micrograms/ml hydrocortisone suppressed IFN gamma production completely in both groups. Our results corroborate those investigations that showed no influence of the compound on T cell effector mechanisms. The attenuation of humoral immunophenomena, however, suggest a very specific point of action within the immune system by Ciamexone. PMID- 1900220 TI - [Nutrition and patients with cancer]. PMID- 1900221 TI - Kistrin, a polypeptide platelet GPIIb/IIIa receptor antagonist, enhances and sustains coronary arterial thrombolysis with recombinant tissue-type plasminogen activator in a canine preparation. AB - BACKGROUND: Kistrin is a 68-amino acid polypeptide from the venom of the Malayan pit viper Agkistrodon rhodostoma, which inhibits the platelet GPIIb/IIIa receptor. Its effect on thrombolysis, reocclusion, and bleeding associated with administration of recombinant tissue-type plasminogen activator (rt-PA) was studied in a canine model of coronary artery thrombosis. METHODS AND RESULTS: Coronary patency was monitored for 2 hours by ultrasonic flow probe and repeated coronary angiography. The rt-PA was given as 0.45-mg/kg bolus injections at 15 minute intervals until recanalization or to a maximum of four boluses. Four groups of four or five dogs were studied: a control group that received intravenous heparin (4,000-unit bolus and 1,000 units each hour) and three groups that received heparin and 0.48, 0.24, or 0.12 mg/kg kistrin, administered as a 10% bolus injection and an infusion during a 60-minute period. In the control group, reflow occurred in four of five dogs within 37 +/- 47 minutes but was followed by cyclic reflow and reocclusion. Kistrin at a dose of 0.48 and 0.24 mg/kg reduced the time to reflow to 6 +/- 5 and 10 +/- 3 minutes, respectively, and abolished reocclusion. With 0.12 mg/kg kistrin, reflow occurred in all four animals, within 27 +/- 23 minutes, and reocclusion occurred in two animals. Kistrin induced a dose-related prolongation of the template bleeding time: with 0.48 mg/kg kistrin, the bleeding time was prolonged from 3.8 +/- 1.3 minutes before infusion to 29 +/- 2 minutes during infusion, but it was shortened to 8.3 +/- 2.6 minutes at 90 minutes after the end of infusion. Kistrin also caused a dose-related inhibition of platelet aggregation with ADP and collagen: with 0.48 mg/kg kistrin, platelet aggregation was abolished during the infusion but had partially recovered toward the end of the observation period. Pathological examination of recanalized coronary arterial segments of dogs given 0.48 or 0.24 mg/kg kistrin revealed widely patent arteries with some platelets layered on the damaged intimal surface. CONCLUSIONS: Kistrin increases the rate and extent of thrombolysis with a reduced dose of rt-PA, and it prevents reocclusion. At an effective dose, it is associated with a transient prolongation of the bleeding time and inhibition of platelet aggregation. Kistrin may offer promise as adjunctive treatment to thrombolytic agents in patients with acute myocardial infarction. PMID- 1900222 TI - Relative efficacy of antithrombin compared with antiplatelet agents in accelerating coronary thrombolysis and preventing early reocclusion. AB - BACKGROUND: Optimal coronary thrombolysis should be prompt and persistent. Although activation of platelets and increased thrombin activity have been associated with clinical thrombolysis, the role of each in delaying thrombolysis or inducing early coronary reocclusion has been difficult to define. METHODS AND RESULTS: In conscious dogs with coronary thrombosis induced by electrical current, we assessed the impact on the rapidity of thrombolysis and the incidence of reocclusion of two types of adjunctive treatment given concomitantly with intravenous tissue-type plasminogen activator (t-PA): 1) inhibition of platelet function with a peptide mimetic antagonist of platelet glycoprotein IIb/IIIa receptors or with lysine acetylsalicylic acid (ASA) and 2) inhibition of thrombin activity with recombinant hirudin or with heparin. ASA but not the receptor antagonist shortened the time to thrombolysis with t-PA (20 +/- 13 [mean +/- SD] minutes with ASA, 36 +/- 15 minutes with receptor antagonist, and 43 +/- 16 minutes with the saline control). Reocclusion occurred promptly after completion of the infusion of t-PA in all seven dogs given saline. Reocclusion was delayed and prevented in some dogs within 90 minutes after the end of the infusion of t PA by both antiplatelet agents but still occurred in 42% despite continued inhibition of platelet function (i.e., three of six dogs given ASA and two of six given receptor antagonist). In contrast, inhibition of thrombin activity with recombinant hirudin in a dose that prolonged the partial thromboplastin time modestly (1.5-2-fold) resulted in accelerated lysis (19 +/- 10 minutes) and prevention of reocclusion in each of six dogs. Heparin given in doses that elicited similar prolongation of the partial thromboplastin time did not accelerate lysis nor prevent reocclusion, which occurred in five of six dogs. CONCLUSIONS: Inhibition of thrombin by recombinant hirudin facilitates thrombolysis and maintains patency of coronary arteries recanalized with t-PA particularly effectively. The benefit conferred may reflect direct anticoagulant effects plus diminished activation of platelets secondary to decreased thrombin activity. PMID- 1900223 TI - Influence of coronary collateral vessels on myocardial infarct size in humans. Results of phase I thrombolysis in myocardial infarction (TIMI) trial. The TIMI Investigators. AB - BACKGROUND: The influence of coronary collateral vessels on infarct size in humans remains controversial, partly because no previous study has examined the impact of collaterals present at the onset of acute myocardial infarction on infarct size. METHODS AND RESULTS: The present study used the data base of the Thrombolysis in Myocardial Infarction (TIMI) Phase I trial to correlate the presence or absence of angiographically documented collaterals in the initial hours of myocardial infarct evolution with the size of the infarct as assessed by serial measurements of serum creatine kinase (CK). To avoid the confounding effects of reperfusion on enzymatic estimates of infarct size, this report is limited to those 125 patients who failed to recanalize at 90 minutes after administration of tissue plasminogen activator or streptokinase. Patients with angiographically documented collaterals (group A, n = 51) had significantly lower values of peak serum CK than patients without collaterals (group B, n = 74) (1,877 +/- 216 versus 2,661 +/- 212 IU/l, respectively [mean +/- SEM], p = 0.004). Similarly, CK-derived infarct size estimates were significantly lower in group A than in group B (20.6 +/- 2.5 versus 31.4 +/- 2.8 CK gram equivalents, p = 0.001). The infarct size observed in patients with collaterals was less for anterior infarctions as well as for infarctions of other locations; thus, the beneficial effects of collaterals were independent of the site of the infarct. In 65 of the 125 patients who failed to reperfuse, left ventricular ejection fraction (LVEF) was assessed by contrast ventriculography both at initial cardiac catheterization (before thrombolytic therapy) and at hospital discharge. Among the patients who had both studies, global LVEF tended to increase from pretreatment to hospital discharge in group A (from 50.6 +/- 1.8% to 53.4 +/- 1.8%, p = 0.10) but decreased in group B patients (from 50.3 +/- 1.8% to 47.8 +/- 1.7%, p = 0.02). At hospital discharge, global LVEF was greater in patients with coronary collaterals (53.5 +/- 1.7% versus 49.6 +/- 1.7%, p = 0.01). CONCLUSIONS: The results demonstrate that, in patients in whom thrombolytic therapy fails to induce reperfusion, the presence of coronary collateral vessels at the onset of myocardial infarction is associated with limitation of infarct size as assessed enzymatically and with improved ventricular function on discharge as assessed by LVEF. PMID- 1900224 TI - Noninvasive quantification of regional myocardial blood flow in coronary artery disease with oxygen-15-labeled carbon dioxide inhalation and positron emission tomography. AB - BACKGROUND: Oxygen-15-labeled water is a diffusible, metabolically inert myocardial blood flow tracer with a short half-life (2 minutes) that can be used quantitatively with positron emission tomography (PET). The purpose of this study was to validate a new technique to quantify myocardial blood flow (MBF) in animals and to assess its application in patients. METHODS AND RESULTS: The technique involves the administration of 15O-labeled carbon dioxide (C15O2) and rapid dynamic scanning. Arterial and myocardial time activity curves were fitted to a single tissue compartment tracer kinetic model to estimate MBF in each myocardial region. Validation studies consisted of 52 simultaneous measurements of MBF with PET and gamma-labeled microspheres in nine closed-chest dogs over a flow range of 0.5-6.1 ml/g/min. A good correlation between the two methods was obtained (y = 0.36 + 1.0x, r = 0.91). Human studies consisted of 11 normal volunteers and eight patients with chronic stable angina and single-vessel disease, before and after intravenous dipyridamole infusion. In the normal group, MBF was homogeneous throughout the left ventricle both at rest and after administration of dipyridamole (0.88 +/- 0.08 ml/g/min and 3.52 +/- 1.12 ml/g/min, respectively; p less than or equal to 0.001). In patients, resting MBF was similar in the distribution of the normal and stenotic arteries (1.03 +/- 0.23 and 0.93 +/- 0.21 ml/g/min, respectively). After dipyridamole infusion, MBF in normally perfused areas increased to 2.86 +/- 0.83 ml/g/min, whereas in the regions supplied by stenotic arteries it increased to only 1.32 +/- 0.27 ml/g/min (p less than or equal to 0.001). CONCLUSIONS: PET with C15O2 inhalation provides an accurate noninvasive quantitative method for measuring regional myocardial blood flow in patients. PMID- 1900225 TI - Increased thrombin levels during thrombolytic therapy in acute myocardial infarction. Relevance for the success of therapy. AB - BACKGROUND: It has been suggested that thrombolysis in a feedback reaction may generate pro-coagulant activities. METHODS AND RESULTS: Fifty-five patients were treated with urokinase-preactivated prourokinase (n = 35) or tissue-type plasminogen activator (n = 20) for acute myocardial infarction and underwent coronary angiography at 90 minutes and at 24-36 hours into thrombolysis, and fibrinogen (Ratnoff-Menzie), D-dimer (ELISA) and thrombin-antithrombin III complex levels (ELISA) were measured. Primary patency was achieved in 39 patients (70.9%), 13 of whom (33.3%) suffered early reocclusion. Nonsignificant decreases in fibrinogen levels were observed while D-dimer levels increased +3,008 +/- 4,047 micrograms/l (p less than 0.01), differences not being significant in respect to the thrombolytic agents or to the clinical course. In contrast, while thrombin-antithrombin III complex levels decreased -4.4 +/- 13.0 micrograms/l in patients with persistent patency, they increased +7.5 +/- 13.6 micrograms/l in case of nonsuccessful thrombolysis (p less than 0.02) and +11.9 +/- 23.8 micrograms/l in case of early reocclusion (p less than 0.001). For patients with thrombin-antithrombin III complex levels greater than 6 ng/l 120 minutes into thrombolysis, the unfavorable clinical course was predicted with 96.2% sensitivity and 93.1% specificity. CONCLUSION: Generation of thrombin, occurring during thrombolysis, is a major determinant for the success of therapy and thrombin-antithrombin III levels may serve as predictors for the short-term prognosis. PMID- 1900226 TI - Capnography in pulmonary embolism diagnosis. PMID- 1900227 TI - A new class of reversible cell cycle inhibitors. AB - The effects of three compounds on the cell cycle of HL-60 promyeloid leukemia cells has been examined. Ciclopirox olamine, an antifungal agent, and the compound Hoechst 768159 reversibly block the cell cycle at a point occurring roughly 1 h before the arrest mediated by aphidicolin, an inhibitor of DNA polymerase alpha activity, which acts in early S phase. Similar results are also obtained with the compound mimosine, a plant amino acid. Based on these data, it is concluded that all three agents inhibit cell cycle traverse at or very near the G1/S phase boundary and identify a previously undefined reversible cell cycle arrest point. PMID- 1900228 TI - Simultaneous quantification of c-myc oncoprotein, total cellular protein, and DNA content using multiparameter flow cytometry. AB - Variations in total cellular protein content can confound interpretation of the significance of modulations of specific cellular proteins. In an effort to overcome this problem, a technique is described for the simultaneous measurement of a specific cellular protein, total cellular protein, and DNA content. The method utilizes dual-laser (uv and 488 nm) excitation and three fluorescent dyes: FITC, SR101, and DAPI. FITC-labelled antibody coupled with indirect immunofluorescence was used to quantify the c-myc oncoprotein, whereas SR101 and DAPI were used to measure total cellular protein and cellular DNA, respectively. Flow cytometric measurements of c-myc oncoprotein were compared to densitometric readings of p64c-myc. SR101 protein determinations were compared to those obtained by the Lowry technique. Results indicated that flow cytometric measurements correlated well with those obtained by the biochemical methods. The usefulness of the technique was further examined following treatment of exponentially growing HL-60 cells with 2.5 micrograms/ml cycloheximide for 0 to 12 h. Cycloheximide treatment was found to cause a significant decrease in c-myc oncoprotein content within 2 h (P less than 0.05), a relative increase in the proportion of G0/G1 cells and a modest decrease in total cellular protein. This technique appears to provide a rapid, quantitative approach, useful for investigating alterations in cellular growth balance occurring with cell differentiation, neoplastic transformation, or cell treatment with radiation or cytostatic drugs. PMID- 1900229 TI - Interferon-gamma inhibits thyroid-stimulating hormone-induced morphological changes and induces the expression of major histocompatibility complex class II antigen in thyroid follicles in suspension culture. AB - The effects of interferon-gamma (IFN gamma) on the morphology of thyroid follicles and the expression of major histocompatibility complex (MHC) class II antigens were examined. The thyroid follicles were suspended in RPMI-1640 containing 10% fetal calf serum with or without IFN gamma (200 U/ml). After culture for 5 days, follicles were incubated in the presence of TSH (10 mU/ml) for 1 h and fixed for electron microscopic and immunohistochemical examination. Regardless of the presence of IFN gamma, suspended follicles became inverted within 5 days. However, MHC class II antigens were expressed only in inverted follicles cultured with IFN gamma. In inverted follicles cultured without IFN gamma, TSH stimulation induced remarkable morphological changes, such as elongation of microvilli and an appearance of pseudopods. On the other hand, the follicles cultured with IFN gamma showed poor response to TSH. Thus, IFN gamma induced the expression of MHC class II antigens of cultured thyroid follicles and inhibited TSH-induced morphological changes in the cells. PMID- 1900230 TI - Activin-binding protein is present in pituitary. AB - A binding protein for activin was purified from bovine pituitary by affinity chromatography on dextran sulfate-Sepharose CL-4B and activin-Affi-Gel 10. A 52,700-fold purification over the starting crude homogenate was achieved. The purified preparation showed two bands of 36 and 33 kilodalton in sodium dodecyl sulfate-polyacrylamide gel electrophoresis under nonreducing conditions. The ability of each form of the protein to specifically bind activin was determined by ligand blot analysis and binding competition study. Each protein was found to have the same NH2-terminus and its sequence was identical to that of follistatin, which is a specific inhibitor of identical to that of follistatin, which is a specific inhibitor of FSH release. Moreover, the binding protein was shown to inhibit the spontaneous FSH release from cultured pituitary cells as does follistatin. These properties are the same as activin-binding protein that we have obtained from rat ovary. These results support a conclusion that activin binding protein/follistatin exists also in the pituitary. Activin-binding protein has an ability to inhibit the activin-induced augmentation of FSH release from cultured pituitary cells as does inhibin. However, the inhibitory pattern by the binding protein was quite distinct from that of inhibin, suggesting that there may be different mechanism(s) for their antagonistic actions. Stoichiometric inhibition as shown by gel filtration analysis indicates that activin-binding protein binds activin to form an inactive equimolar complex having neither stimulatory nor inhibitory activity for FSH secretion by the pituitary. These findings suggest that activin is actually involved in FSH secretion in the pituitary and that the activin action in the pituitary is regulated by activin binding protein/follistatin. PMID- 1900231 TI - Endogenous excitatory amino acid involvement in the preovulatory and steroid induced surge of gonadotropins in the female rat. AB - The physiological role of N-methyl-D-aspartate (NMDA) receptors in the regulation of preovulatory and steroid-induced surges of gonadotropins in the female rat was examined. The specific and potent noncompetitive NMDA receptor antagonist MK801 was used for blockade of NMDA neurotransmission. MK801 treatment completely inhibited the ability of progesterone to induce LH and FSH surges in the estrogen primed ovariectomized rat. Administration of MK801 on proestrus in the immature female rat primed with PMSG resulted in a significant attenuation of the proestrous LH, FSH, and PRL surge and a corresponding attenuation of ovulation. Similarly, in the adult cycling female rat, MK801 administration on proestrus led to a significant attenuation of the proestrous LH and PRL surges. Mean FSH levels were lower in MK801-treated adult rats than in vehicle-treated rats, but this effect was not significant. In the estrogen-primed ovariectomized immature rat, the agonist NMDA caused a rapid (less than 10 min) elevation of LH and FSH in vivo. The gonadotropin-releasing effect of NMDA may be mediated at the level of the hypothalamus, since the medial basal hypothalamus/preoptic area of NMDA treated rats killed 3 and 5 min post-NMDA had a significantly greater release of GnRH in vitro than that of vehicle-treated rats. In conclusion, these findings demonstrate that the preovulatory gonadotropin surge in the female rat is dependent on NMDA neurotransmission for its expression and add further evidence for a critically important role for NMDA receptors in the physiological regulation of gonadotropin secretion in the female rat. PMID- 1900232 TI - Effect of recombinant inhibin on luteinizing hormone and follicle-stimulating hormone secretion in the rat. AB - We investigated the effect of the iv injection of recombinant human (rh) inhibin on FSH and LH secretion in the female rat under various experimental circumstances. Rh inhibin caused dose-related decreases in mean plasma FSH, but not LH, levels in ovariectomized female rats 14 days old and older. The duration of this inhibition was proportional to the dose of rh inhibin, but no consistent changes in FSH secretion were observed until 4 h after treatment. Maximum suppression of FSH release was observed at about 15 micrograms rh inhibin/kg BW and lasted 8-10 h. Measurement of the area under the curve from 4-12 h after injection of inhibin indicated a dose-related decrease in total FSH secreted. When blood samples were withdrawn every 10 min to evaluate pulsatile gonadotropin release, analysis of FSH pulse parameters indicated that rh inhibin (25 micrograms/kg) interfered with pulse frequency, amplitude, and peak levels in both intact and ovariectomized rats. In contrast, pulsatile LH secretion was not measurably altered. These results demonstrate that rh inhibin acts primarily at the level of the pituitary to inhibit all parameters of FSH secretion and suggest that this effect is at least not entirely mediated by changes in GnRH receptors. PMID- 1900233 TI - Marked differences in immunocytological localization of [3H]estradiol-binding protein in rat pancreatic acinar tumor cells compared to normal acinar cells. AB - [3H]Estradiol can bind to a specific protein in normal rat pancreatic acinar cells. Electron microscopic immunocytochemical analysis has shown this protein to be localized primarily in the rough endoplasmic reticulum and mitochondria. Rat exocrine pancreatic tumor cell lines, whether grown in tissue culture (AR42J) or as a tumor mass after sc injection into rats (DSL-2), lacked detectable amounts of this [3H]estradiol-binding protein (EBP), as determined by the dextran-coated charcoal assay. Furthermore, primary exocrine pancreatic neoplasms induced with the carcinogen azaserine contained little or no detectable [3H]estradiol-binding activity. However, electron immunocytochemical studies of transformed cells indicated the presence of material that cross-reacted with antibodies prepared against the [3H]EBP. The immunopositive reaction in transformed cells was localized almost exclusively in lipid granules. Such lipid organelles in normal acinar cells, although present less frequently than in transformed cells, have never been observed to contain EBP-like immunopositive material. Presumably, the aberrant localization of EBP in these acinar tumor cells results in loss of function of this protein, which in normal pancreatic acinar cells appears to exert a modulating influence on zymogen granule formation and the process of secretion. PMID- 1900234 TI - Expression of ovarian inhibin during pregnancy in the rat. AB - We have examined the expression of the rat inhibin genes in the maternal ovary during pregnancy. RNA blot analysis indicates that the inhibin-alpha chain mRNA is expressed in the ovary throughout gestation at levels comparable to those observed in cycling rats. In situ hybridization shows that the inhibin-alpha and beta A mRNAs are produced in the granulosa cells of developing antral follicles; little or no hybridization to functional corpora lutea is observed. Early in pregnancy, a large number of follicles hybridize to both alpha- and beta A inhibin cDNA probes. Many of these follicles undergo atresia during the first half of pregnancy, and the number of inhibin-expressing follicles reaches a nadir on day 15. This is followed by an increase in inhibin-producing follicles, which peaks just before parturition. The increase in inhibin-expressing follicles observed in late pregnancy corresponds to a small rise in serum inhibin levels, as measured using an alpha chain-specific RIA. After the first postpartum ovulation, few hybridizing follicles are observed. Ovariectomy in either early (day 6) or mid (day 15) pregnancy results in a significant fall in serum inhibin levels and a robust increase in serum FSH levels 9 h after surgery. These results suggest that inhibin is produced by the maternal ovary during pregnancy, that its synthesis is modulated during late gestation, and that inhibin may play a role in regulating FSH secretion during pregnancy. PMID- 1900235 TI - Evidence for an autocrine role of activin B within rat anterior pituitary cultures. AB - Activins, dimers of inhibin beta subunits, are potent stimulators of FSH secretion in vivo and in vitro and of FSH beta mRNA expression in rat anterior pituitary cultures. In this study, we investigated the possibility that locally secreted activin B (beta B beta B) may function as an autocrine modulator of basal FSH secretion and expression based on the previous observation that beta B is expressed within gonadotropes. The incubation of cultured rat anterior pituitary cells with a m mouse monoclonal antibody specific for the activin B homodimer (MAb-activin B) significantly attenuated the basal secretion of FSH in a concentration- and time-dependent manner, without influencing LH secretion. Moreover, MAb-activin B selectively inhibited FSH beta mRNA accumulation without affecting either LH beta or alpha subunit mRNAs. The MAb-activin B completely blocked the stimulation of FSH secretion by exogenous activin B, but not by activin A, confirming its specificity. As previously shown, inhibin A and follistatin significantly suppressed basal FSH secretion in these cultures. This inhibitory effect, albeit of lower magnitude, was still evident even in the presence of the MAb-activin B which by itself suppressed basal FSH secretion. These data suggest that the secretion of activin B by the gonadotropes of the anterior pituitary may serve as an autocrine signal in the selective modulation of FSH expression and secretion. Furthermore, the inhibitory actions of inhibins and follistatins on gonadotropes may, in part, be explained by their ability to interfere with the actions of endogenous activin B. PMID- 1900236 TI - Thrombin cleavage analysis of a novel antihaemophilic factor variant, factor VIII delta II. AB - Factor VIII delta II is a genetically engineered deletion variant of factor VIII expressed by recombinant Chinese hamster ovary cells, in which a major portion of the central (B) domain and a part of the light chain (Pro771-Asp1666) are missing. After immunoaffinity purification, the kinetics of thrombin cleavage of the novel molecule was analysed by SDS/PAGE, Western blotting and N-terminal amino acid sequencing. Thrombin first cleaves factor VIII delta II at Arg740 Ser741 to generate the 90-kDa heavy chain and an 80-kDa fusion polypeptide consisting of the remaining portion of the B domain and the 73-kDa light chain. The 90-kDa fragment is further cleaved, giving rise to 50-kDa and 40-kDa fragments while the 80-kDa fragment generates a 71/73-kDa doublet. The 71/73-kDa doublet, 50-kDa and 40-kDa fragments were further analysed by N-terminal amino acid sequencing and found to correspond to the predicted amino acid sequences. Our study shows that, in spite of the 900 amino acid deletion present in factor VIII delta II, the essential structural elements required for thrombin activation are conserved. PMID- 1900237 TI - Linking phospholipase A2 to phospholipid turnover and prostaglandin synthesis in mast cell granules. AB - Rapid incorporation of exogenous arachidonic acid into phospholipid has been detected in conjunction with eicosanoid synthesis by purified mast cell granules [Chock, S. P. & Schmauder-Chock, E. A. (1988) Biochem. Biophys. Res. Commun. 156, 1308-1315]. The species of phospholipid formed has now been identified primarily as phosphatidylinositol. A calcium-dependent phospholipase A2 has also been detected in the secretory granule. This enzyme, like the cyclooxygenase [Schmauder-Chock, E. A. & Chock, S. P. (1989) J. Histochem. Cytochem. 37, 1319 1328], appears to bind tightly to the granule matrix components. It is heat resistant and requires millimolar concentrations of calcium for optimal activity. It prefers phosphatidylinositol over phosphatidylcholine as substrate. Since the granule contains a large amount of phospholipid, the action of this phospholipase A2 can provide the required substrate for the arachidonic acid cascade. These findings provide the basis for linking phospholipase A2 to the production of eicosanoids during granule exocytosis. Since the granule also contains both an active acylating system that can rapidly reacylate lysophosphatidylinositol to form phosphatidylinositol, and an active phospholipase A2 which hydrolyzes phosphatidylinositol, a rapid turnover involving the fatty acid at the sn-2 position of phosphatidylinositol may occur. These findings are consistent with our postulation that the secretory granule is the source and/or the cause of many of the early biochemical events associated with the process of stimulus-secretion coupling. PMID- 1900238 TI - Isolation and inactivation of the nuclear gene encoding the rotenone-insensitive internal NADH: ubiquinone oxidoreductase of mitochondria from Saccharomyces cerevisiae. AB - We have recently described the isolation of a mitochondrial rotenone-insensitive NADH:ubiquinone oxidoreductase from Saccharomyces cerevisiae [de Vries, S. & Grivell, L. A. (1988) Eur. J. Biochem. 176, 377-384]. We now report the isolation of the nuclear gene encoding this single-subunit enzyme. Null mutants have been constructed by means of one-step gene disruption. Oxygen-uptake experiments, performed with mitochondria isolated from the mutant cells, showed that this NADH dehydrogenase catalyzes the oxidation of NADH generated inside the mitochondrion. Inactivation of this NADH dehydrogenase does not affect growth on glucose and ethanol, but growth on lactate, pyruvate and acetate is impaired or absent. This phenotype is discussed in terms of the interplay between different metabolic pathways in yeast. PMID- 1900239 TI - Ileal Peyer's patch emigrants are predominantly B cells and travel to all lymphoid tissues in sheep. AB - The ileal Peyer's patch (PP) was selectively labeled with fluorescein isothiocyanate by extracorporeal perfusion in 7-12 week-old lambs and the lymphocyte lineage and fate of the emigrants was determined by fluorescence microscopy and flow cytometry. PP emigrants were found in all tissues examined, accounting for 10%-15% of ileal mesenteric lymph node (MLN). 1%-2% of jejunal MLN, jejunal PP, prescapular lymph node (PLN) and 3%-4% of spleen cells. All ileal PP emigrants enter the ileal MLN on their way to the circulation. Removal of the MLN prior to perfusion enabled emigrants to go directly to the circulation and extravasate in distant tissues faster than in intact animals. The ileal MLN might provide an additional level of regulation for ileal PP emigrants. The perfused ileal PP contained about 25 times more B cells than T cells. The emigrant cells found in different tissues included both T and B cells but came to reflect, although to a lesser degree, the B cell composition of the tissue from which they were derived. One day after perfusion the composition of PP emigrants was similar to that of the tissue within which they were found; the spleen was the exception with a bias towards B cells. By day 3 the ratio of B to T cells in the PP emigrants was 1 for jejunal MLN and PLN. 1.5 for ileal MLN and jejunal PP, and 4-5 for the spleen and blood. It was concluded that the PP-derived T cells were recirculating T cells that were in the ileal PP at the time of perfusion. These cells emigrated rapidly and equilibrated such that they accounted for about 1.5% of the T cell pool in various tissues. Most PP-derived B cells were probably produced in the PP. The greatest contribution (24.4%) that ileal PP emigrants made to the B cell pool of a tissue was with the ileal MLN through which they are obliged to pass. The contribution was lower but still very significant in blood (8.9%), spleen (6.8%), PLN (3.9%), jejunal MLN (3.5%) and jejunal PP (1.8%). There was no evidence that ileal PP emigrants made a greater relative contribution to either T or B cell populations in MLN or jejunal PP than to non gut-associated sites. The B cells were distributed throughout the immune system, which is in accordance with the proposal that the ileal PP is a site of primary B cell genesis in sheep. PMID- 1900240 TI - Cytokine interactions in experimental cutaneous leishmaniasis. Interleukin 4 synergizes with interferon-gamma to activate murine macrophages for killing of Leishmania major amastigotes. AB - We investigated the effect of recombinant murine interleukin 4 (IL 4) in the absence or presence of recombinant murine interferon-gamma (IFN-gamma) on adherent bone-marrow macrophages (M phi), peritoneal exudate and resident peritoneal M phi from susceptible BALB/c M phi, which were pulse-infected with Leishmania major amastigotes (AM), IL 4 (5-100 U/ml) failed to activate any of these M phi populations for killing of intracellular AM. However, in the presence of low concentrations of IFN-gamma (10-20 U/ml), which alone caused only a slight or intermediate reduction of the number of intracellular parasites. IL 4 led to a dramatic increase of the parasite elimination by all M phi populations. In the case of resident peritoneal M phi, the synergism of IFN-gamma and IL 4 required the incubation of the M phi with both cytokines or with IFN-gamma alone for at least 10 h prior to infection; adding both cytokines after infection of the M phi did not cause a significant reduction of the intracellular parasite burden. The synergistic effect of IL 4 and IFN-gamma was completely abrogated in the presence of anti-IL 4 antibodies. Furthermore, there was no significant difference between M phi derived from either susceptible BALB/c or from resistant C57BL/6 mice. Evidence is presented that the synergistic action of IL 4 and IFN-gamma occurs via an L-arginine-dependent killing pathway. From these data we conclude that IL 4 provides a strong stimulus for the killing of intracellular L. major AM provided low concentrations of IFN-gamma are present. Also, IFN-gamma is apparently an important priming signal for the activation of resident M phi to eliminate intracellular AM. PMID- 1900241 TI - Growth of Mycobacterium avium in human monocytes: identification of cytokines which reduce and enhance intracellular microbial growth. AB - Human monocytes were isolated by standard procedures and their ability to harbor growth of two virulent strains of Mycobacterium avium, TMC724 and TMC7479, was assessed in the absence or presence of cytokines. Both strains of mycobacteria, especially the M. avium TMC7479, grew progressively in untreated human monocytes. Inclusion of certain macrophage-activating cytokines, such as interferon-gamma in the presence of indomethacin or 1.25(OH2)-vitamin D3 (calcitriol) led to significant reductions in bacterial growth at 7 days post-infection. Conversely, treatment of human monocytes with interleukin-(IL) 1, macrophage-colony stimulating factor or IL 3 led to an increased permissiveness of these cells for M. avium. Moreover, these cytokines were shown to increase dramatically extracellular M. avium growth in vitro in tissue culture medium. Further, inclusion of antibodies against IL 1 beta and IL 6 in untreated infected monocytes monolayers led to a reduced growth of M. avium, suggesting that infected monocytes produce factors which enhance their susceptibility to M. avium. Overall, my findings suggest that cytokines may play a bidirectional role in atypical mycobacterial infections, by either increasing or decreasing resistance of the monocyte. PMID- 1900242 TI - Avian CD4 and CD8 interact with a cellular tyrosine protein kinase homologous to mammalian p56lck. AB - Functional as well as immunochemical studies have indicated that chicken T lymphocytes express surface antigens homologous to mammalian CD4 and CD8. The results presented in this report demonstrate that the avian CD4 and CD8 homologs are physically associated with a cellular tyrosine protein kinase related to mammalian p56lck. Furthermore, they show that engagement of either avian CD4 or CD8 is associated with a rapid intracellular tyrosine phosphorylation signal, suggesting that the function of these surface molecules may be mediated through alterations of the associated tyrosine protein kinase. Taken together, these findings demonstrate that the associations of CD4 and CD8 with an intracellular tyrosine protein kinase are evolutionarily conserved, further enhancing the likelihood that they are critical for normal immune functions. PMID- 1900243 TI - Expression of a novel type of immunoglobulin C lambda transcripts in human mature B lymphocytes producing kappa light chains. AB - Ordered rearrangement of immunoglobulin genes (heavy chain then kappa and eventually lambda genes) is observed during B lymphocyte ontogeny. Unexpectedly, we found that human mature B cells producing kappa chains and having germ-line lambda genes contain lambda mRNA consisting of an invariant 5' region (herein termed X) and of one of the classical C lambda exons. The X region of these transcripts originates from a unique exon located 5 kb upstream of the J-C lambda 1 gene segment. X-C lambda mRNA expression occurs without somatic DNA rearrangement. The use of the X DNA fragment as a probe allows definition of a family of human genes that comprises at least four members and includes the first exon of the lambda 14.1 gene. The latter is selectively transcribed in pre-B lymphocytes and directs the synthesis of a lambda-like chain. In contrast, the X C lambda transcripts do not appear to encode a C lambda-related polypeptide in mature B cells. Thus, despite a 73% homology extending far beyond the exon sequences, the X and lambda 14.1 genes are expressed at different stages of B cell development and might serve different functions. PMID- 1900244 TI - 1-(substituted)benzyl-5-aminoimidazole-4-carboxamides are potent orally active inhibitors of Trypanosoma cruzi in mice. AB - 1-(Substituted)benzyl-5-aminoimidazole-4-carboxamides are potent orally active inhibitors of Trypanosoma cruzi infections in mice. The most active compounds are the 1-(4-chlorobenzyl)- and 1-(3,4-dichlorobenzyl)-analogs (L-153,094 [2] and L 153,153 [4], resp.) which are approximately 7-fold more potent upon oral administration than nifurtimox (Lampit) in suppressing parasite levels in the blood of mice with acute Trypanosoma cruzi infections. PMID- 1900245 TI - Chromatosomes are not produced from Tetrahymena chromatin by micrococcal nuclease digestion. AB - The subnucleosomal organization of Tetrahymena chromatin, which has an unusual H1 histone, was investigated by NaCl extraction and micrococcal nuclease digestion of nuclei. It was found that Tetrahymena histone H1 is extracted with 0.35 M NaCl, whereas bovine thyroid H1 is not. Micrococcal nuclease digestion of Tetrahymena nuclei did not yield chromatosomes as a stable intermediate, whereas digestion of bovine thyroid nuclei did. PMID- 1900246 TI - Effect of actinomycin D on Trypanosoma cruzi. AB - Viable metacyclic forms of T. cruzi, Y strain, treated with an adequate dose of actinomycin D (50 micrograms Act-D/ml/10(7) parasites/ml for 72 h at 28 degrees C) showed the following properties: 1) they lost their ability to replicate in culture medium, in blood and in tissues of normal mice and were no longer able to incorporate tritiated thymidine; 2) they could not penetrate into Vero cells and could not replicate inside normal macrophages; 3) they retained their immunogenicity and the ability to protect mice against a virulent infection; 4) they did not induce histological lesions as described in chronic experimental Chagas' disease. PMID- 1900247 TI - Effect of some alkaline phosphatase inhibitors on intestinal calcium transfer. AB - 1. There is a good correlation between the capacity of sugars to stimulate calcium transfer and their capacity to be phosphorylated by the intestinal alkaline phosphate with a part of the phosphate liberated from an ester phosphate. 2. On the sugar dependent and sugar independent calcium transfer, inhibitors of this enzyme act differently. 3. Phosphate, a competitive inhibitor suppresses both transfers. 4. Only the dependent sugar transfer was suppressed with phloridzin acting competitively at the sugar site, or with EDTA which could react close to the active site. 5. L-phenylalanine and phenobarbital, not competitive inhibitors does not act on either type of calcium transfer, the sugar dependent or the sugar independent. PMID- 1900248 TI - Hypoxemic stimulation of heart glycogen synthase and synthesis. Effects of insulin and diabetes mellitus. AB - With radiotracer and 13C nuclear magnetic resonance (13C-NMR) methods, we studied the time course of glycogen resynthesis after three 90-s episodes of hypoxemia in both control and diabetic rats in vivo. Glycogen synthesis was measured in the presence and absence of infused insulin and compared with the changes in glycogen synthase (GS) and phosphorylase activities. We observed in 13C-NMR spectra the expected mobilization of glycogen during hypoxia in vivo. In control rats with or without exogenous insulin, this was followed by a rapid resynthesis of glycogen during a 40-min recovery period. A marked activation of GS was observed by 10 min (glucose-6-phosphate-independent form of GS [GSl] = 0.65 mumol.min-1.g-1 or 92% of total GS), and activation persisted up to 40 min in both groups. Glycogen synthesis during the recovery period averaged 0.51 and 0.45 mumol.min-1.g-1 in the saline- and insulin-treated rats, respectively. In the diabetic rats by 10 min after hypoxemia, GSl increased only modestly in both saline-treated (0.16 mumol.min-1.g-1) and insulin-treated (0.21 mumol.min-1.g-1) rats, and activation persisted up to 40 min only with insulin treatment. Glycogen synthesis was slower in the diabetic rats given insulin (0.28 mumol.min-1.g-1) and essentially absent in the saline-treated rats (0.03 mumol.min-1.g-1) compared with controls. We conclude that recovery from hypoxemia is accompanied by a marked activation of GSl and rapid rates of glycogen synthesis in nondiabetic rats, and diabetes markedly blunts this response. Acute insulin infusion only partially overcomes this block.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1900250 TI - Nucleotide sequence of the exo-1,3-beta-glucanase-encoding gene, EXG1, of the yeast Saccharomyces cerevisiae. AB - The nucleotide (nt) sequence of the Saccharomyces cerevisiae gene (EXG1) encoding extracellular exo-1,3-beta-glucanases (EXG) I and II was determined. An open reading frame of 1344 bp codes for a 448-amino acid (aa) polypeptide, with a calculated Mr of 51,307, which contains two potential N-glycosylation sites. The EXG1 DNA hybridizes to a 1.7-kb transcript whose 5' end maps to a position 98 bp upstream from the site of initiation of protein synthesis. Comparison of the N terminal aa sequence deduced from the nt sequence with that of the purified EXGII revealed the existence of an extra 40-aa peptide in the precursor protein containing a Lys-Arg peptidase-processing site at the junction with the mature, extracellular form. The N-terminal region of the putative precursor is a very hydrophobic segment with structural features resembling those of signal peptides of secreted proteins. The Mr of the mature EXG polypeptide deduced from the nt sequence is 46,385. The 5'- and 3'-flanking regions of the EXG1 gene have structural features in common with other yeast genes. PMID- 1900249 TI - A yeast protein with homology to the beta-subunit of G proteins is involved in control of heme-regulated and catabolite-repressed genes. AB - The product of the Saccharomyces cerevisiae AER2 gene is responsible for maintaining repression of at least two distinct regulatory pathways: heme activation/repression and catabolite repression. Mutations in the gene caused an eightfold increase in the expression of the heme-activated CYC1 gene in the absence of heme, a substantial increase in the expression of the heme-repressed ANB1 gene in the presence of heme, and a 13-fold increase in the expression of the catabolite-repressed GAL1 gene in the presence of glucose. Lesser or no increases in the expression of these genes were observed under derepressed or activation conditions. The aer2 mutations also caused a large increase in CYC7 gene expression under all conditions; this gene is subject to heme activation/repression, as well as catabolite repression. The AER2 gene was cloned and the sequence determined. The large open reading frame contiguous with the transcript from the complementing region encoded a 713-amino acid polypeptide chain with extensive homology to the beta-subunit of G proteins. The sequence revealed that AER2 is the TUP1 gene. A deletion mutation was constructed and the null phenotype was the same as the original mutants. The aer2 null mutant was shown to have increased aerobic and anaerobic levels of RNA encoding the ROX1 repressor, normally expressed only aerobically and responsible for the aerobic repression of ANB1 expression. The increase in both ROX1 and ANB1 RNAs aerobically in this mutant suggests that the repressor is nonfunctional in the mutant. PMID- 1900251 TI - Multiple alternatively spliced transcripts of the mouse tyrosinase-encoding gene. AB - We have isolated and characterized tyrosinase-specific cDNAs from wild-type mouse skin, to provide a basis for the structural and functional analysis of mutations at the mouse tyrosinase-encoding (Tyr) locus. The cDNAs were synthesized by the polymerase chain reaction. At least twelve alternatively spliced transcripts of the Tyr gene were found, including nine not previously described. Of 51 clones obtained, most (59%) correspond to the full-length cDNA encoding active tyrosinase. The others are shorter and apparently arose by alternative splicing. They are attributable to exon skipping, usage of alternative 5' and/or 3' splice sites, and (in one case) retention of an intronic sequence. Patterns of alternative splicing also occur in other pigmented tissues. PMID- 1900252 TI - An examination of the effect of pretreatment of rats with Sacoglottis gabonensis bark extract, a Nigerian palmwine additive, and ethanol on macromolecular binding of aflatoxin B1. AB - In a previous study (Okoye and Neal, Food and Chemical Toxicology 1988, 26, 679) enhanced ethanol-induced reductions in albumin-bound and unbound serum aflatoxin B1 (AFB1) and increased hepatic DNA-AFB1 binding were observed in rats treated with bark extract of Sacoglottis gabonensis, a Nigerian palmwine additive. The present study was designed to examine further the mechanism of these effects. Male weanling rats were pretreated with the bark extract or ethanol, or both, in drinking-water (at three times the levels used in the previous study) for 8 days before the ip administration of a single dose of [3H]AFB1. [In the previous study the rats were fed all three compounds simultaneously.] In contrast to the results of the previous study, when both the additive and ethanol were administered, there were no significant effects on [3H]AFB1 binding to liver or serum albumin or liver DNA. The levels of DNA-bound aflatoxin were reduced in rats given the additive or ethanol alone. PMID- 1900253 TI - Inactivation of aflatoxin B1 in corn meal, copra meal and peanuts by chlorine gas treatment. AB - More than 75% degradation of aflatoxin B1 (AFB1) was achieved after treatment of AFB1-spiked corn meal, spiked copra meal (the residue of the kiln-dried coconut kernels after mechanical expulsion of oil) and peanuts artificially infected with Aspergillus parasiticus, with 11, 16 and 35 mg chlorine gas per g meal or peanuts, respectively. At these chlorine gas treatment levels, extension of the exposure period of the corn meal and copra meal beyond 2.5 hr, and the peanuts beyond 1 day, did not increase the percentage degradation of AFB1. The mutagenicity of chlorine-treated copra meal and peanuts spiked with AFB1 was greatly reduced compared with untreated controls, as determined in Salmonella typhimurium strain TA98 in the presence of rat liver S-9 mix; the reduction in mutagenicity was found to be highly correlated with the reduction in AFB1 levels. Reactions of chlorine with AFB1 or constituents of the meals or peanuts did not appear to generate new mutagenic compounds. The moisture content of the meals and peanuts appeared to be an important factor affecting the degradation of AFB1 by chlorine gas. PMID- 1900254 TI - Recombinant human alpha-interferon in patients with chronic non-A, non-B hepatitis: a multicenter randomized controlled trial from France. AB - We have conducted a multicenter randomized controlled trial comparing two doses of recombinant human alpha-interferon for efficacy in 60 patients with chronic non-A, non-B hepatitis. The source of infection appeared to be transfusion in 30 patients, intravenous drug abuse in 16 patients and was unknown in 14 patients. Patients were randomly assigned to no treatment or to treatment with either 1 or 3 MU of alpha-interferon given three times a week for 24 wk. Forty-five patients (75%) were positive for antibody to hepatitis C virus. During the 24-wk treatment period, mean serum ALT levels decreased in both treatment groups, but the decrease was statistically significant only in the 3 MU group. However, at 24 wk, the proportion of patients with normal ALT levels was similar in the 3 MU group (39%) and the 1 MU group (45%), and both were significantly higher than in controls (0%). Repeat liver biopsy specimens showed a significant decrease in the severity of histological changes in the 3 MU group but not in the 1 MU group or in controls. Responses to alpha-interferon did not correlate with patient's age, gender, source of infection, pretreatment serum ALT, presence of anti-hepatitis C virus or cirrhosis. After treatment, the mean ALT levels rose in both treated groups. The proportion of patients with normal ALT levels at wk 48 was 28% in the 3 MU group and 20% in the 1 MU group. In conclusion, a dose of 3 MU was superior to 1 MU of alpha-interferon given three times weekly for 24 wk in inducing improvements in serum ALT levels and liver histological examinations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1900255 TI - Hyperdynamic circulation in a chronic murine schistosomiasis model of portal hypertension. AB - Chronic murine schistosomiasis is a natural disease model of portal hypertension closely mimicking the clinical and histological features of human hepatic schistosomiasis. We studied the splanchnic and systemic hemodynamics in the murine model of schistosomiasis by radioactive microsphere technique. Mice infected with 60 cercariae of Schistosoma mansoni (n = 8) were studied hemodynamically 11 wk after the infection and were compared with age-matched healthy controls (n = 11). Mean portal venous inflow in the infected mice (3.82 +/- 0.32 ml/min) was 61% higher than in the healthy animals (2.37 +/- 0.25 ml/min; p less than 0.01). A twofold increase in hepatic arterial flow was also seen in mice with schistosomiasis (0.47 +/- 0.14 ml/min) as compared with controls (0.16 +/- 0.03 ml/min; p less than 0.05), whereas splanchnic arteriolar resistance (60.91 +/- 7.64 vs. 101.21 +/- 11.06 mm Hg.min.ml-1.gm; p less than 0.05) and peripheral vascular resistance (112.05 +/- 14.05 vs 254.53 +/- 29.86 mm Hg.min.ml-1.gm; p less than 0.01) were reduced. There was a significant increase in cardiac index (752 +/- 99 vs. 453 +/- 55 ml.min-1.kg body weight-1; p less than 0.05) and reduction in mean arterial pressure (81.37 +/- 3.09 vs. 101.45 +/- 5.85 mm Hg; p less than 0.05) in the infected animals compared with controls. These observations clearly demonstrate the existence of a hyperdynamic circulatory state in this model of portal hypertension. PMID- 1900256 TI - Therapy of chronic hepatitis C with alpha-interferon: the answer? Or more questions? PMID- 1900258 TI - Chemical sympathectomy alters the development of hypertension in miniature swine. AB - To determine if the neurotoxin 6-hydroxydopamine could be used to chemically sympathectomize neonatal miniature swine, eight newborn swine were treated with 6 hydroxydopamine beginning on the first day after birth and continuing at regular intervals for the next 6 months. Six littermates served as controls and received vehicle injections. A significant reduction in the pressor response to intravenous tyramine (95%) and in the tissue norepinephrine content of the kidneys, left ventricle, and gastrocnemius muscle (more than 93%) provided evidence for an effective long-term sympathectomy in the 6-hydroxydopamine treated animals. In addition, the blood pressure response of these young, chemically sympathectomized swine to chronic deoxycorticosterone acetate treatment was evaluated. Mean arterial pressure before deoxycorticosterone was similar in the 6-hydroxydopamine-treated (116 +/- 2 mm Hg) and control (125 +/- 5 mm Hg) groups. One week after deoxycorticosterone, mean arterial pressure had risen significantly by 20-22 mm Hg in both groups. Blood pressure continued to increase in the control group, reaching a value of 163 +/- 6 mm Hg by the third week after treatment. In contrast, mean arterial pressure in the 6 hydroxydopamine group did not increase further during weeks 2 and 3 after deoxycorticosterone. In conclusion, chronic treatment of neonatal swine with 6 hydroxydopamine produced an animal model with an effective, general, peripheral sympathectomy. The significant attenuation of the hypertensive response in these sympathectomized animals lends further support to the hypothesis that an intact sympathetic nervous system is necessary for the full expression of deoxycorticosterone hypertension in miniature swine. PMID- 1900257 TI - Localization of the human Rh blood group gene structure to chromosome region 1p34.3-1p36.1 by in situ hybridization. AB - A cDNA clone, RhIXb (1384 bp), encoding the entire protein sequence of a human blood group Rh polypeptide has been used to map the Rh locus, by in situ hybridization, to the region p34.3-p36.1 of chromosome 1. Two other unrelated cDNA clones, pUCA2 (750 bp) and pUCIII (1600 bp), isolated during the cloning procedure of the Rh cDNA were investigated simultaneously, and assigned to chromosome 3p21.1-3p22 (clone pUCA2) and to chromosome 22q12.1-22q13.1 (clone pUCIII). PMID- 1900259 TI - High density lipoprotein turnover in patients with hypertension. AB - Although hyperinsulinemia and decreased high density lipoprotein cholesterol concentration can occur in patients with hypertension, there is no information available concerning the dynamic state of high density lipoprotein metabolism. To address this issue, we quantified high density lipoprotein turnover in 12 patients with mild hypertension and 11 matched subjects with normal blood pressure. Patients with high blood pressure had lower high density lipoprotein cholesterol concentrations. Fractional catabolic rates of 125I-apolipoprotein AI (apoAI)/high density lipoprotein were faster in patients with hypertension (0.36 +/- 0.02 versus 0.26 +/- 0.02 l/day, p less than 0.001). Total synthetic rates of apoAI were also significantly greater in patients with high blood pressure (17.4 +/- 1.1 versus 13.2 +/- 0.6 mg/kg/day, p less than 0.001). Although significant correlation was observed between blood pressure and fractional catabolic rate of 125I-apoAI/high density lipoprotein in the experimental population (r = 0.52, p less than 0.01), no relation was found when patients with normal blood pressure or hypertension were considered separately. However, a highly significant positive correlation was found between 125I-apoAI/high density lipoprotein fractional catabolic rate and insulin concentration in the entire population (r = 0.72, p less than 0.001). In conclusion, the patients with mild hypertension studied were hyperinsulinemic, had a faster fractional catabolic rate of 125I apoAI/high density lipoprotein, and a lower high density lipoprotein-cholesterol concentration. It is suggested that the changes seen in high density lipoprotein cholesterol concentration and 125I-apoAI/high density lipoprotein fractional catabolic rates were secondary to the hyperinsulinemia and not due to the high blood pressure per se. PMID- 1900260 TI - End-tidal carbon dioxide measurement in emergency medicine and patient transport. PMID- 1900261 TI - Relation between estrogen receptor and malignancy of thyroid cancer. AB - The relationship between the histological grade of dedifferentiation of thyroid cancer and estrogen receptors (ER) was examined immunohistochemically. Thyroid cancers were from postmenopausal females of almost the same mean age (69-73 years old) and within the same period of time (1974-1983). ER immunoreactivity located in the nucleus of the epithelium was found in all 6 well differentiated papillary cancers, and 5 of them (83.3%) showed ER-immunoreactive (ER-IR) cells amounting to 20 or more per visual field (x 100) under a light microscope. Of the 6 cases of poorly differentiated papillary cancer, 5 (83.3%) had 1-19 ER-IR cells per visual field. ER-IR cells were negative in 5 out of 6 cases (83.3%) of anaplastic cancers. Thus, the number of ER-IR cells tended to decrease with the degree of atypism of thyroid cancer (P less than 0.001). PMID- 1900262 TI - Expression of membrane-associated lymphotoxin/tumor necrosis factor-beta on human lymphokine-activated killer cells. AB - A membrane-associated lymphotoxin (LT)-related molecule was detected on human lymphokine-activated killer (LAK) cells by flow cytometric analysis. Kinetic analysis revealed that the LT antigenicity on LAK cells appeared at 9 h after the beginning of culture and was maintained thereafter. By autoradiography, the molecular weight of membrane LT was estimated to be 31 kD and/or 62 kD. PMID- 1900263 TI - The effect of mass screening for breast cancer: results of a multivariate analysis. AB - To evaluate the life-prolonging effect of mass screening for breast cancer, we compared the risk of death for the patients detected by mass screening with that for the patients diagnosed in out-patient clinics, after adjusting for other relevant factors simultaneously by using the Cox regression model. A multivariate analysis using the Cox regression model in which clinical staging of disease was taken as one of the independent variables, showed that the risk of death for patients detected by mass screening was smaller by 0.765 times than that for patients found in out-patient clinics although the reduction was not statistically significant. This small reduction might be partly due to the effect of mass screening through early detection even within the same stage, and partly due to length bias, lead time bias and self-selection bias. When clinical staging of disease was removed from the independent variables, the risk of death for patients detected by mass screening was reduced from 0.765 times to 0.677 times that for patients diagnosed in out-patient clinics, which was statistically significant (P greater than 0.01). For asymptomatic patients detected by mass screening, such as reduction of the risk of death was from 0.789 times to 0.555 times that for patients found in out-patient clinics (P less than 0.05). These results suggest that mass screening for breast cancer may contribute to the reduction of the risk of death, although the effect of biases inherent in periodic screening was not removed completely in the present analysis. PMID- 1900264 TI - Prognostic factors for surgically treated lung adenocarcinoma patients, with special reference to smoking habit. AB - Prognostic factors for lung adenocarcinoma patients who had been treated surgically at the Center for Adult Diseases, Osaka, in 1978-87 (N = 267) were analyzed in terms of year of operation, sex, age at operation, postsurgical stage, grade of differentiation, and smoking habit. Survival was improved for later year of operation (1983-87), younger age at operation, stage I or II, well or moderately differentiated adenocarcinoma, and nonsmoking status in univariate analysis. A proportional hazards model including the above variables showed that stage III and stage IV patients had 4.06 and 8.81 times higher risk of death compared to stage I and II patients. Poorly differentiated adenocarcinoma showed 2.01 times higher risk of death than well or moderately differentiated adenocarcinoma. Earlier year of operation and female status showed 1.70 and 1.82 times higher risk of death, respectively, as compared to each reference group. All these hazard ratios showed statistical significance. Current smokers who smoked 1,000 or more on the cigarette index showed 2.38 times higher risk of death than nonsmokers with statistical significance. This indicates that smoking is another independent prognostic factor for patients who undergo operations for adenocarcinoma of the lung. PMID- 1900265 TI - In vitro progression-associated c-H-ras activation in neoplastic hepatocyte lines established from SV40-T antigen gene-harboring transgenic mice. AB - In order to investigate the molecular mechanisms of multistep hepatocarcinogenesis in SV40-T antigen gene-harboring transgenic mice, 9 hepatocellular carcinoma (HCC) lines and 10 "preneoplastic" hepatocyte lines were established from the animals and their biological and molecular changes during culture were investigated. Three of the 9 HCC lines showed progression during culture in terms of growth rate and growth capability in soft agar and in nude mice. This progression was associated with the appearance of activated c-H-ras oncogene. Including these 3 lines, H-ras activation was observed in a total of 7 of the 9 HCC lines (78%), whereas it was found only in 1 of 10 (10%) "preneoplastic" hepatocyte lines. These data thus indicate that H-ras activation may be an event occurring at a relatively late stage of hepatocarcinogenesis in this transgenic mouse system and that it may serve towards completion of the carcinogenic process together with the T-antigen. PMID- 1900266 TI - Multiple primary cancers in patients with squamous cell carcinoma of the oral cavity. AB - During the 27 years between 1962 and 1988, 984 patients visited the National Cancer Center Hospital for previously untreated squamous cell carcinoma of the oral cavity and lip. The records of all these 984 patients were reviewed to determine the incidence of additional primary carcinoma. 1) One hundred and thirty-five additional carcinomas developed in 111 patients (11.2%) during 5,689.2 person-years of observation. The incidence of additional primary carcinoma was 23.7 per 1,000 person-years. 2) The cumulative rate of additional primary carcinoma during the first five years of observation showed a tendency to increase in the most recently treated patients (from 1980 to 1988). 3) The observed-to-expected ratio (O/E ratio) for all sites was 2.77 and this is significantly high (P less than 0.01). The calculation of the O/E ratio for each site revealed significantly high risks in the oral cavity and pharynx, esophagus and skin. The O/E ratio for the oral cavity and pharynx was extremely high (79.45). 4) The O/E ratio for all sites in each year of follow-up was the highest in the first year, stayed nearly constant from the second to 14th years, and decreased gradually afterwards. Significantly high risk was observed until the 13th year of follow-up. Patients with oral squamous cell carcinoma must be under frequent and regular examination for almost 15 years. PMID- 1900267 TI - Action site of the gene determining susceptibility to propylnitrosourea-induced thymic lymphomas in F344 rats. AB - To clarify whether the determining effect of the thymic lymphoma susceptible-1 (Tls-1) gene is on putative N-propyl-N-nitrosourea (PNU) target cells among T lineage cells or on other host factors, we investigated the PNU-induced lymphomagenesis in transplantation chimeras between susceptible F344 and resistant LES strain rats. Administration of PNU to lethally irradiated (F344 x LES)F1 rats reconstituted with bone marrow cells from either F344 or LES parental rats invariably led to development of donor-origin thymic lymphomas. On the other hand, thymic lymphomas were induced in thymectomized F1 rats grafted with neonatal LES thymus, of which 4 out of 8 were of the donor origin. These observations indicate that the target cells of thymic lymphomagenesis of F344 and LES rats were equally susceptible to PNU provided they are in susceptible hosts and the LES thymus seems capable of supporting thymic lymphomagenesis, although this capability wanes with aging of the thymus. The effect of the Tls-1 gene, therefore, is neither on PNU susceptibility of the target cells nor on the capability of the thymus to support lymphomagenesis, but on other host factors either in or out of the thymus. PMID- 1900268 TI - Two types of DNA ligase I activity in lymphoblastoid cells from patients with Bloom's syndrome. AB - DNA ligases I and II were separated by hydroxylapatite (HA) column chromatography in cell-free extracts of lymphoblastoid cell lines (LCLs) derived from two unrelated patients with Bloom's syndrome (BS) and two healthy individuals. The specific activity of ligase I from the crude extract was consistently lower in GM3403, a BS LCL from an Ashkenazi Jewish patient, than in normal control LCLs. By contrast, the level of ligase I activity in BSL-2KA, another BS LCL derived from a Japanese patient, was equivalent to those in normal LCLs, although GM3403 and BSL-2KA shared the feature of exceedingly high frequency of spontaneous sister-chromatid exchange. The levels of total ligase activity in crude extracts without the separation into the two forms, however, were approximately two-fold higher for the two BS LCLs than for the normal LCLs. Partial purification by chromatography on a DEAE-cellulose 23 column and a phosphocellulose column did not affect the superiority of the two BS LCLs over the normal LCLs in the specific activity of the total ligases. Nonetheless, subsequent application to an HA column again resulted in much less elevation of the specific activity of ligase I for GM3403 than for BSL-2KA and control LCLs. The levels of ligase II activity, accounting for 4-13% of total ligase activity, were similar among the LCLs examined. Irrespective of the extent of purification, essentially no difference in the heat lability of DNA ligase I was detected among the four LCLs. These findings suggest that there may exist among BS LCLs at least two types of subtle abnormality of DNA ligase I itself and/or a putative substance modulating the enzyme function. PMID- 1900269 TI - High-level expression of human c-jun gene causes cellular transformation of chicken embryo fibroblasts. AB - To analyze the transforming activity of c-jun, a Rous sarcoma virus (RSV) variant that carries human c-jun instead of v-src (JH1) was constructed. After infection onto chicken embryo fibroblasts (CEF), JH1 formed foci with a titer comparable to that of wild-type RSV, and the infected cells grew in soft agar, indicating that the human c-jun gene has transforming potential, like the v-jun gene. The expression of Fra-2, one of the recently isolated Fos-related antigens, but not Fos was detected in both JH1-infected CEF and CEF infected with the control retrovirus vector (DS3). Gel shift analysis using nuclear extracts from DS3 infected CEF revealed that the Fra-2/Jun complex contributes to the basal level of AP-1 DNA binding activity. A similar activity was detected in JH1-infected CEF, but these cells have an additional AP-1 binding activity derived from Jun homodimers that seems to play important roles in the cellular transformation. PMID- 1900270 TI - bcl-2 translocation in Japanese B cell lymphoma: novel bcl-2 translocation with immunoglobulin heavy chain diversity segment. AB - Breakpoints of a lymphoma case with bcl-2 gene rearrangement that did not show comigration of immunoglobulin (Ig) heavy chain joining (JH) fragment were cloned. Sequence analysis revealed that the translocation broke the 3' side of the Ig heavy chain diversity (DH) segment at the heptamer recombination signal and each end was ligated to the bcl-2 locus. Since Southern blot demonstrated that both alleles of JH were rearranged, this translocation was suggested to have occurred at the step of VH-DH, or DH-DHJH recombination, one step later than that of DH-JH recombination where the common pattern of bcl-2 rearrangement generally occurs. Cases that showed comigration with JH fragment were also studied by polymerase chain reaction with 5' bcl-2 oligomer and 3' JH consensus anti-sense oligomer since it has been demonstrated that bcl-2 translocation at the major breakpoint clustering region (mbr) in American cases clusters within an about 150 bp region in the mbr. The results demonstrated that four out of five cases studied were amplified, indicating that the same clustering mechanism exists for Japanese cases. The present study, together with our previous report on Ig kappa-bcl-2, indicated that bcl-2 translocation in Japanese B cell lymphomas might occur at a later stage of B cell development, as compared with that in American cases. Less involvement of bcl-2 in Japanese B cell lymphoma may also be in part explainable by low susceptibility to bcl-2 rearrangement at the step of DH-JH recombination. PMID- 1900271 TI - Organization of mouse DNA polymerase beta gene silencer elements and identification of the silencer-binding factor(s). AB - Different portions of the 5'-upstream region of the mouse DNA polymerase beta gene were combined with bacterial chloramphenicol acetyltransferase (CAT) gene of the CAT vector. Transfection of these recombinant plasmids into mouse NIH/3T3 cells has revealed that each of the previously identified two negatively acting regions (silencers I and II) of this gene consists of multiple sub-domains. The distal silencer (silencer I) at around -1.5 kb consists of four sub-domains ( 1852 to -1667, -1663 to -1616, -1564 to -1525 and -1355 to -1257). The promoter proximal silencer (silencer II) at around -0.5 kb consists of two functional domains (-681 to -523 and -490 to -447) separated by a neutral region of 33 base pairs. Silencer II functioned efficiently when silencer I was deleted. Conversely, the distal silencer I functioned efficiently when silencer II was deleted. Thus, these silencers functioned redundantly to each other in NIH/3T3 cells. Nucleotide sequence analysis revealed no extensive sequence similarity between these two silencers. Significant sequence similarity is present between a distal portion of silencer II and the c-myc gene silencer, and also between a proximal portion of silencer II and the mouse F9 cell-specific silencer. A protein factor(s) that specifically bound to the silencer elements was detected in nuclear extracts of NIH/3T3 cells and mouse liver in which DNA polymerase beta was expressed at a rather low level. The same binding factor(s) can bind to both silencer I and II regions, although its affinity for silencer II is much higher than that for silencer I. PMID- 1900272 TI - Detection of epidermal growth factor receptors and E-cadherins in the basolateral membrane of A431 cells by laser scanning fluorescence microscopy. AB - We have examined the localization of epidermal growth factor (EGF) receptors and E-cadherins in cultured A431 cells, an epidermoid carcinoma cell line, using a laser scanning fluorescence microscope. The fluorescence signals generated by monoclonal antibodies against EGF receptor and E-cadherin were localized mainly in the cell-cell contact sites, about 3 microns in width. When these areas for cell adhesion were scanned perpendicularly, fluorescence was detected from a point 4 microns from the cell base for a distance of 8 microns towards the cell surface (about 16 microns from the cell base). These data suggest the subcellular localization of EGF receptors and E-cadherins in the basolateral membrane of A431 cells. PMID- 1900273 TI - Ciliated gastric cells among Japanese living in Hawaii. AB - A total of 129 consecutive gastrectomy specimens from Japanese (99), Philippinos (11), Hawaiians (8), Koreans (5), Chinese (4) and Caucasians born in Hawaii (2) were examined under high-power light microscopy (1000 x) for the presence of ciliated gastric cells. Fifty-two of the 129 gastrectomy specimens (40.3%) contained ciliated cells. Ciliated cells were found in the basal segments of antral glands (usually cystically dilated) whose superficial segments had undergone intestinal metaplasia. The presence of ciliated cells in the gastric mucosa was influenced by the age of the patient and by the degree of intestinal metaplasia: the older the patient, the greater the degree of intestinal metaplasia and the greater the frequency of specimens with ciliated cells. The presence of ciliated cells was also influenced by the type of lesion in the specimen. Although the highest frequency (47.2%) was found in stomachs removed for adenocarcinoma, a substantial number of stomachs removed for gastric ulcer also showed that change (36%). The data suggest that increasing age and advanced atrophic gastritis, especially of the antrum, provide the necessary conditions that lead to the development of cilia, not only in Japanese subjects, but in other Hawaiian ethnic groups as well. PMID- 1900274 TI - A new rat colon cancer cell line metastasizes spontaneously: biologic characteristics and chemotherapeutic response. AB - A new cell line (RCN-9) was established in culture from a transplantable rat colon adenocarcinoma, which was induced in the colon of a male Fischer F344 rat by subcutaneous administration of 1,2-dimethylhydrazine. When RCN-9 cells were injected subcutaneously or into the cecal subserosa of syngeneic rats, carcinomas with progressive growth were obtained and the development of lung (63.6%) and liver (40.0%) metastases, respectively, ensued. Antitumor effects of 5 fluorouracil (5-FU), adriamycin (ADM) and mitomycin C (MMC) against RCN-9 were examined in vivo and in vitro. 5-FU and ADM had antitumor effects both in vivo and in vitro; MMC had antitumor effects in vitro. These results show that the RCN 9 cell line can be used both as a model to study mechanisms of metastasis from colon carcinoma and as a model in chemotherapeutic studies of metastatic disease from colon carcinoma. PMID- 1900275 TI - Mechanism of metabolic abnormality of thyroid hormones in Walker 256 carcinosarcoma-bearing rats. AB - We examined the mechanism of abnormality of thyroid hormone metabolism in Walker 256 carcinosarcoma-bearing rats. The serum levels of thyroxine (T4), 3,5,3' triiodothyronine (T3) and thyroid-stimulating hormone (TSH), and the responses of serum T4 and T3 to exogenous TSH in tumor-bearing rats on day 14 after inoculation of tumor cells were significantly less than those in pair-fed control (PFC) rats, suggesting that the metabolic abnormality of thyroid hormones may be caused by disorder of both peripheral and central functions, and that a certain tumor-derived factor may be involved in this abnormality. An active factor responsible for the metabolic abnormality was found in soluble cytosol fraction (SF) of the tumor cells. Administration of the SF to normal rats significantly reduced their serum T4 and T3 concentrations, liver 5'-deiodinase (5'-DI) activity, responsiveness of the thyroid gland to TSH and food intake compared with those of PFC rats, but, unlike the tumor, did not reduce the serum TSH level. This biologically active factor in the SF was found to be a heat-labile protein and specific to the tumor. It was tentatively named serum thyroid hormone reducing factor (STRF). STRF was partially purified from the SF by ammonium sulfate fractionation and DEAE-cellulose chromatography. Partially purified STRF preparation significantly diminished the serum T4 and T3 concentrations and liver 5'-DI activity and food intake of normal rats compared with those of PFC rats, mimicking the changes associated with the tumor in tumor-bearing animals. These results suggested that abnormality of thyroid hormone metabolism in tumor-bearing animals may partly be caused by STRF-mediated modulation at peripheral and thyroid gland levels. Whether STRF actually induces anorexia remains to be clarified. PMID- 1900276 TI - In vitro determination of the effect of indoleglycerol phosphate on the interaction of purified TrpI protein with its DNA-binding sites. AB - Expression of the trpBA gene pair of Pseudomonas aeruginosa is regulated by the endogenous level of indoleglycerol phosphate (InGP) and the trpI gene product. The TrpI protein binds to the -77 to -32 region of the trpBA promoter. This region is divisible into two sites: site I, which is protected by TrpI in the presence and absence of InGP; and site II, which is protected by TrpI only in the presence of InGP. Recently, the trpI gene was subcloned into an expression vector and the protein was overproduced in Escherichia coli. The TrpI protein was purified to 80 to 95% purity. The molecular weight of native TrpI protein is estimated to be 129,000 by gel exclusion chromatography, and therefore it is likely a tetramer composed of 31,000-dalton monomers. Gel retardation assays with the purified TrpI protein demonstrated that InGP increases the affinity of TrpI for sites I and II approximately 17- and 14-fold, respectively. Binding of TrpI to site I is site II independent. However, the protein has low intrinsic affinity for site II and its binding to site II is site I dependent. Therefore, binding of TrpI to site II probably requires its interaction with a second TrpI molecule at site I. PMID- 1900277 TI - Positive FNR-like control of anaerobic arginine degradation and nitrate respiration in Pseudomonas aeruginosa. AB - A mutant of Pseudomonas aeruginosa was characterized which could not grow anaerobically with nitrate as the terminal electron acceptor or with arginine as the sole energy source. In this anr mutant, nitrate reductase and arginine deiminase were not induced by oxygen limitation. The anr mutation was mapped in the 60-min region of the P. aeruginosa chromosome. A 1.3-kb chromosomal fragment from P. aeruginosa complemented the anr mutation and also restored anaerobic growth of an Escherichia coli fnr deletion mutant on nitrate medium, indicating that the 1.3-kb fragment specifies an FNR-like regulatory protein. The arcDABC operon, which encodes the arginine deiminase pathway enzymes of P. aeruginosa, was rendered virtually noninducible by a deletion or an insertion in the -40 region of the arc promoter. This -40 sequence (TTGAC....ATCAG) strongly resembled the consensus FNR-binding site (TTGAT....ATCAA) of E. coli. The cloned arc operon was expressed at low levels in E. coli; nevertheless, some FNR-dependent anaerobic induction could be observed. An FNR-dependent E. coli promoter containing the consensus FNR-binding site was expressed well in P. aeruginosa and was regulated by oxygen limitation. These findings suggest that P. aeruginosa and E. coli have similar mechanisms of anaerobic control. PMID- 1900278 TI - Synthesis of a Bacillus subtilis small, acid-soluble spore protein in Escherichia coli causes cell DNA to assume some characteristics of spore DNA. AB - Small, acid-soluble proteins (SASP) of the alpha/beta-type are associated with DNA in spores of Bacillus subtilis. Induction of synthesis of alpha/beta-type SASP in Escherichia coli resulted in rapid cessation of DNA synthesis, followed by a halt in RNA and then protein accumulation, although significant mRNA and protein synthesis continued. There was a significant loss in viability associated with SASP synthesis in E. coli: recA+ cells became extremely long filaments, whereas recA mutant cells became less filamentous. The nucleoids of cells with alpha/beta-type SASP were extremely condensed, as viewed in both light and electron microscopes, and immunoelectron microscopy showed that the alpha/beta type SASP were associated with the cell DNA. Induction of alpha/beta-type SASP synthesis in E. coli increased the negative superhelical density of plasmid DNA by approximately 20%; UV irradiation of E. coli with alpha/beta-type SASP gave reduced yields of thymine dimers but significant amounts of the spore photoproduct. These changes in E. coli DNA topology and photochemistry due to alpha/beta-type SASP are similar to the effects of alpha/beta-type SASP on the DNA in Bacillus spores, further suggesting that alpha/beta-type SASP are a major factor determining DNA properties in bacterial spores. PMID- 1900279 TI - Acquisition of thymidylate by the obligate intracytoplasmic bacterium Rickettsia prowazekii. AB - The pathway for the acquisition of thymidylate in the obligate bacterial parasite Rickettsia prowazekii was determined. R. prowazekii growing in host cells with or without thymidine kinase failed to incorporate into its DNA the [3H]thymidine added to the culture. In the thymidine kinase-negative host cells, the label available to the rickettsiae in the host cell cytoplasm would have been thymidine, and in the thymidine kinase-positive host cells, it would have been both thymidine and TMP. Further support for the inability to utilize thymidine was the lack of thymidine kinase activity in extracts of R. prowazekii. However, [3H]uridine incorporation into the DNA of R. prowazekii was demonstrable (973 +/- 57 dpm/3 x 10(8) rickettsiae). This labeling of rickettsial DNA suggests the transport of uracil, uridine, uridine phosphates (UXP), or 2'-deoxyuridine phosphates, the conversion of the labeled precursor to thymidylate, and subsequent incorporation into DNA. This is supported by the demonstration of thymidylate synthase activity in extracts of R. prowazekii. The enzyme was determined to have a specific activity of 310 +/- 40 pmol/min/mg of protein and was inhibited greater than or equal to 70% by 5-fluoro-dUMP. The inability of R. prowazekii to utilize uracil was suggested by undetectable uracil phosphoribosyltransferase activity and by its inability to grow (less than 10% of control) in a uridine-starved mutant cell line (Urd-A) supplemented with 50 microM to 1 mM uracil. In contrast, the rickettsiae were able to grow in Urd-A cells that were uridine starved and supplemented with 20 microM uridine (117% of control). However, no measurable uridine kinase activity could be measured in extracts of R. prowazekii. Normal rickettsial growth (92% of control) was observed when the host cell was blocked with thymidine so that the host cell's dUXP pool was depressed to a level inadequate for growth and DNA synthesis in the host cell. Taken together, these data strongly suggest that rickettsiae transport UXP from the host cell's cytoplasm and that they synthesize TTP from UXP. PMID- 1900281 TI - Cloning, phenotypic expression, and DNA sequence of the gene for lactacin F, an antimicrobial peptide produced by Lactobacillus spp. AB - Lactacin F is a heat-stable bacteriocin produced by Lactobacillus acidophilus 11088. A 63-mer oligonucleotide probe deduced from the N-terminal lactacin F amino acid sequence was used to clone the putative laf structural gene from plasmid DNA of a lactacin F-producing transconjugant, L. acidophilus T143. One clone, NCK360, harbored a recombinant plasmid, pTRK160, which contained a 2.2-kb EcoRI fragment of the size expected from hybridization experiments. An Escherichia coli-L. acidophilus shuttle vector was constructed, and a subclone (pTRK162) containing the 2.2-kb EcoRI fragment was introduced by electroporation into two lactacin F-negative strains, L. acidophilus 89 and 88-C. Lactobacillus transformants containing pTRK162 expressed lactacin F activity and immunity. Bacteriocin produced by the transformants exhibited an inhibitory spectrum and heat stability identical to those of the wild-type bacteriocin. An 873-bp region of the 2.2-kb fragment was sequenced by using a 20-mer degenerate lactacin F specific primer to initiate sequencing from within the lactacin F structural gene. Analysis of the resulting sequence identified an open reading frame which could encode a protein of 75 amino acids. The 25 N-terminal amino acids for lactacin F were identified within the open reading frame along with an N-terminal extension, possibly a signal sequence. The lactacin F N-terminal sequence, through the remainder of the open reading frame (57 amino acids; 6.3 kDa), correlated extremely well with composition analyses of purified lactacin F which also predicted a size of 51 to 56 amino acid residues. Molecular characterization of lactacin F identified a small hydrophobic peptide that may be representative of a common bacteriocin class in lactic acid bacteria. PMID- 1900280 TI - Effect of a 20-kilodalton protein from Bacillus thuringiensis subsp. israelensis on production of the CytA protein by Escherichia coli. AB - CytA, a 27-kDa cytolytic crystal protein of Bacillus thuringiensis subsp. israelensis, is produced only at very low levels by recombinant Escherichia coli cells unless a 20-kDa B. thuringiensis subsp. israelensis protein is also present (K. M. McLean and H. R. Whiteley, J. Bacteriol. 169:1017-1023, 1987; L. F. Adams, J. E. Visick, and H. R. Whiteley, J. Bacteriol. 171:521-530, 1989). However, the data reported here demonstrate that the 20-kDa protein is not required for high level CytA production in E. coli strains carrying mutations in rpoH, groEL, or dnaK, all of which affect the proteolytic ability of the cells. The 20-kDa protein also increases the amount of CryIVD (another B. thuringiensis subsp. israelensis crystal protein) and LacZX90 (a mutant of beta-galactosidase) made by E. coli. The latter phenomenon is attributable to an increase in the half-life of LacZX90, suggesting that the 20-kDa protein may stabilize this protein. The effect of the 20-kDa protein was also examined in vitro and in a T7 RNA polymerase expression system, and the possible significance of these results for the timing of proteolysis and of 20-kDa protein activity is discussed. Finally, the ability of a single antibody to coimmunoprecipitate CytA and the 20-kDa protein from E. coli extracts provides evidence for a protein-protein interaction that may be related to the mechanism of action of the 20-kDa protein. PMID- 1900283 TI - UGA can be decoded as tryptophan at low efficiency in Bacillus subtilis. AB - Replacement of cat-86 codon 7 or 144 with the UGA codon permitted the gene to confer chloramphenicol resistance in wild-type Bacillus subtilis. UAA replacements of the same codons resulted in a chloramphenicol-sensitive phenotype in wild-type B. subtilis and a chloramphenicol-resistant phenotype in suppressor positive strains. N-terminal sequencing showed that UGA at codon 7 was decoded as tryptophan in wild-type cells, at an efficiency of about 6%. PMID- 1900282 TI - Mapping of the gene for a major penicillin-binding protein to a genetically conserved region of the Bacillus subtilis chromosome and conservation of the protein among related species of Bacillus. AB - Penicillin-binding protein 5 is the most abundant penicillin-binding protein in the vegetative membranes of Bacillus subtilis and accounts for 95% of the D,D carboxypeptidase activity of the cell. The structural gene for penicillin-binding protein 5 was mapped to a genetically conserved region near guaB at 0 degrees on the B. subtilis chromosome, and immunoassays revealed that there is conservation of this major penicillin-binding protein among related species. PMID- 1900284 TI - On the reversible interaction of plasminogen activator inhibitor-1 with tissue type plasminogen activator and with urokinase-type plasminogen activator. AB - The reaction between plasminogen activators and plasminogen activator inhibitor-1 is characterized by an initial rapid formation of an inactive reversible complex. The second-order association rate constant (k1) of complex formation of recombinant two-chain tissue-type plasminogen activator (rt-PA) or recombinant two-chain urokinase-type plasminogen activator (rtcu-PA) by recombinant plasminogen activator inhibitor-1 (rPAI-1) is 2.9 +/- 0.4 x 10(7) M-1 s-1 (mean +/- S.D., n = 30) and 2.0 +/- 0.6 x 10(7) M-1 s-1 (n = 12), respectively. Different molecular forms of tissue- or urokinase-type plasminogen activator which do not form covalent complexes with rPAI-1, including rt-PA-Ala478 (rt-PA with the active-site Ser478 mutagenized to Ala) and anhydro-urokinase (rtcu-PA with the active-site Ser356 converted to dehydroalanine) reduced k1 in a concentration-dependent manner, compatible with 1:1 stoichiometric complex formation between rPAI-1 and these ligands. The apparent dissociation constant (KD) of the complex between rPAI-1 and rt-PA-Ala478, determined as the concentration of rt-PA-Ala478 which reduced k1 to 50% of its control value, was 3 5 nM. Corresponding concentrations of active-site-blocked two-chain rt-PA were 150-250-fold higher. The concentration of anhydro-urokinase which reduced k1 to 50% was 4-6 nM, whereas that of active-site-blocked rtcu-PA was 100-250-fold higher. Recombinant single-chain urokinase-type plasminogen activator had an apparent KD of about 2 microM. These results suggest that inhibition of rt-PA or rtcu-PA by rPAI-1 proceeds via a reversible high affinity interaction which does not require a functional active site but which is markedly reduced following inactivation of the enzymes with active-site titrants. PMID- 1900285 TI - The organic functional group in copper-containing amine oxidases. Resonance Raman spectra are consistent with the presence of topa quinone (6-hydroxydopa quinone) in the active site. AB - Resonance Raman spectroscopy has been used to probe the structure of the organic cofactor in copper-containing amine oxidases from bovine plasma, porcine kidney, pea seedlings, and the bacterium Arthrobacter P1. The enzymes were first derivatized with phenylhydrazine or p-nitrophenylhydrazine; resonance Raman spectra were obtained on the intact derivatized enzymes and on a derivatized active-site peptide isolated from bovine plasma amine oxidase. Spectra of the intact amine oxidase phenylhydrazones are practically identical, consistent with the enzymes examined containing a similar cofactor. Only minor frequency shifts and some intensity variations are detected between the resonance Raman spectra of intact bovine plasma amine oxidase and the isolated peptide. These spectral perturbations are attributable to differences in the micro-environment between the intact, folded protein and the isolated small peptide in aqueous solution. This rules out the possibility that a new structure is formed during the isolation of the derivatized active-site peptide. Importantly, the resonance Raman spectra of the phenylhydrazine and p-nitrophenylhydrazine derivatives of the bovine plasma amine oxidase peptide are identical to the spectra of the corresponding derivatives of topa quinone (6-hydroxydopa quinone). Hence these data provide strong, independent support for the recent identification of topa as the organic functional group in bovine plasma amine oxidase (Janes, S. M., Mu, D., Wemmer, D., Smith, A. J., Kaur, S., Maltby, D., Burlingame, A. L., and Klinman, J.P. (1990) Science 248, 981-987). PMID- 1900286 TI - Effects of cholesterol on the function and thermotropic properties of pure UDP glucuronosyltransferase. AB - The effects of cholesterol on the activity and thermal properties of a pure, delipidated isoform of UDP-glucuronosyltransferase were examined after incorporation of enzyme into unilamellar bilayers of distearoylphosphatidylcholine (DSPC) or dioleoylphosphatidylcholine (DOPC). Cholesterol, in bilayers of DSPC, decreased enzyme activity and lowered the temperature (from 37 to 30 degrees C) for a reversible transition from the active form of the enzyme to a less active form. These effects could be separated from each other in that the effect on reversible inactivation of the enzyme occurred at lower concentrations of cholesterol than the effect on activity of the active form of the enzyme. In addition, cholesterol in bilayers of DSPC stabilized UDP glucuronosyltransferase against irreversible thermal inactivation. The extent of stabilization increased with increasing concentration of cholesterol in the bilayers. The effects of cholesterol on UDP-glucuronosyltransferase depended, however, on the nature of the bilayer containing cholesterol. Cholesterol had small effects, if any, on the properties of UDP-glucuronosyltransferase in bilayers of DOPC. PMID- 1900287 TI - Thrombin attenuates the stimulatory effect of histamine on Ca2+ entry in confluent human umbilical vein endothelial cell cultures. AB - Human umbilical vein endothelial cells were grown to confluence, as first passage cells, on coverslips. Treatment with ionomycin or histamine caused a sustained rise in intracellular Ca2+ (measured by Fura-2 fluorescence), but after treatment with thrombin, only a transient rise in Ca2+ was observed. Furthermore, the addition of thrombin after ionomycin or histamine lowered the raised Ca2+ back to near control levels. This effect of thrombin was concentration dependent, with increasing concentrations producing increases in both the rate and extent of the lowering of Ca2+. A similar effect of thrombin was seen on video imaging of Fura 2-loaded cell monolayers. The Ca2(+)-lowering effect of thrombin was not mimicked by phorbol 12-myristate 13-acetate nor blocked by staurosporine, indicating a lack of involvement of protein kinase C; intracellular pH also does not appear to be involved. The mechanism by which thrombin lowers cytoplasmic Ca2+ is due mainly to inhibition of Ca2+ entry since thrombin prevented the stimulated influx of Mn2+ caused by histamine or ionomycin. It may therefore be that in vivo under certain physiological or pathological conditions, thrombin's effects on intracellular Ca2+ are more transient than those of histamine, and thrombin also may induce transience in histamine's actions. PMID- 1900288 TI - The mechanism of nucleosome assembly onto oligomers of the sea urchin 5 S DNA positioning sequence. AB - We have used a model system composed of tandem repeats of Lytechinus variegatus 5 S rDNA (Simpson, R. T., Thoma, F., and Brubaker, J. M. (1985) Cell 42, 799-808) reconstituted into chromatin with chicken erythrocyte core histones to investigate the mechanism of chromatin assembly. Nucleosomes are assembled onto the DNA template by mixing histone octamers and DNA in 2 M NaCl followed by stepwise dialysis into very low ionic strength buffer over a 24-h period. By 1.0 M NaCl, a defined intermediate composed of arrays of H3.H4 tetramers has formed, as shown by analytical and preparative ultracentrifugation. Digestion with methidium propyl EDTA.Fe(II) indicates that these tetramers are spaced at 207 base pair intervals, i.e. one/repeat length of the DNA positioning sequence. In 0.8 M NaCl, some H2A.H2B has become associated with the H3.H4 tetramers and DNA. Surprisingly, under these conditions DNA is protected from methidium propyl EDTA.Fe(II) digestion almost as well as in the complete nucleosome, even though these structures are quite deficient in H2A.H2B. By 0.6 M NaCl, nucleosome assembly is complete, and the MPE digestion pattern is indistinguishable from that observed for oligonucleosomes at very low ionic strength. Below 0.6 M NaCl, the oligonucleosomes are involved in various salt-dependent conformational equilibria: at approximately 0.6 M, a 15% reduction in S20,w that mimics a conformational change observed previously with nucleosome core particles; at and above 0.1 M, folding into a more compact structure(s); at and above 0.1 M NaCl, a reaction involving varying amounts of dissociation of histone octamers from a small fraction of the DNA templates. In low ionic strength buffer (less than 1 mM NaCl), oligonucleosomes are present as fully loaded templates in the extended beads-on-a-string structure. PMID- 1900289 TI - Noncyclooxygenase metabolites of arachidonic acid amplify the vasopressin-induced Ca2+ signal in glomerular mesangial cells by releasing Ca2+ from intracellular stores. AB - Noncyclooxygenase metabolites of arachidonic acid may be potent modulators of the mitogenic response of renal mesangial cells to the mitogenic vasoactive peptide arginine vasopressin (AVP). Since Ca2+ is a critical second messenger in the response of mesangial cells to AVP, and Ca2+ has been implicated in the regulation of growth, we determined whether noncyclooxygenase metabolites altered the phospholipase C-Ca2+ signalling cascade which is activated by AVP. Pretreatment of mesangial cells for 10 min with lipoxygenase and cytochrome P450 monooxygenase inhibitors, nordihydroguaiaretic acid (NDGA, 10(-5) M) or SKF-525A (2.5 x 10(-5) M), but not the cyclooxygenase inhibitor indomethacin (2 x 10(-5) M), reduced the magnitude of the AVP (10(-8) and 10(-7) M)-induced increase in cytosolic free Ca2+ concentration ([Ca2+]i) without affecting inositol trisphosphate production. With 10(-8) M AVP, [Ca2+]i increased to 250 +/- 47 nM in NDGA-treated cells versus 401 +/- 59 nM in control cells (p less than 0.01). [Ca2+]i, measured 2 min after exposure to AVP, was also lower with NDGA (152 +/- 21 nM) when compared with AVP alone (220 +/- 22 nM, p less than 0.01). 14,15 epoxyeicosatrienoic acid (EET) (10(-8) M), which had no effect on inositol trisphosphate production, completely reversed the NDGA-induced inhibition of the [Ca2+]i transient, whereas 5-hydroperoxyeicosatetraenoic acid (HPETE) (5 x 10(-7) M) did not. Pretreatment with higher concentrations of 14,15-EET (10(-7)-10(-6) M) markedly potentiated the AVP-induced increase in [Ca2+]i. NDGA-induced inhibition of the AVP-generated [Ca2+]i transient was also observed when cells were incubated in low Ca2+ media ([Ca2+] less than 5 x 10(-8) M), suggesting that NDGA pretreatment impaired intracellular release of Ca2+. Since NDGA had no direct effect on inositol 1,4,5-trisphosphate-induced Ca2+ release, we postulated that NDGA blocked production of a metabolite that releases Ca2+ from intracellular stores. 14,15-EET and 15-HPETE, but not 15-hydroxyeicosatetraenoic acid (each at 3 x 10(-7) M), raised [Ca2+]i when added directly to cells in low Ca2+ media. In permeabilized cells 14,15-EET and 15-HPETE (10(-7) M) potently released Ca2+ from intracellular stores. In summary, noncyclooxygenase metabolites of arachidonic acid, and in particular P450 metabolites, are potent endogenous amplifiers of the AVP-induced [Ca2+]i signal by mechanisms not directly involving phospholipase C activation. This effect is mediated, at least in part, by enhanced release of Ca2+ from intracellular storage sites by an inositol 1,4,5-trisphosphate-independent mechanism. PMID- 1900290 TI - The product of the rap2 gene, member of the ras superfamily. Biochemical characterization and site-directed mutagenesis. AB - The human rap2 gene encodes a 183 amino acid protein that shares 46% identity with the K-ras p21. Its cDNA was engineered and inserted into the bacterial expression vector ptac; this allowed the production of high levels of soluble recombinant protein in Escherichia coli that was purified to near homogeneity. The rap2 protein binds GTP and exhibits a low intrinsic GTPase activity (rate constant of 0.5 x 10(-2) min-1). It exchanges its bound GDP with a half-life of 18 min at 37 degrees C in the presence of 10 mM Mg2+. Under the same conditions, the dissociation of bound GTP was at least 25-fold slower showing that the rap2 protein has a much higher affinity for GTP than GDP. The contribution of individual domains of the protein to its biochemical activities was investigated by site-directed mutagenesis. Substitution of Val for Gly at position 12 results in a 2-fold decrease in the GDP dissociation rate constant and GTPase activity. Replacement of the Ser at position 17 by Asn severely impairs the GTP binding ability of the protein and points to an important role of this residue in the coordination of Mg2+. Mutation of Thr-35 to Ala results in a decreased affinity for GTP and a reduction (3-fold) of the GTPase activity. Finally, substitution of Thr-145 by Ile leads to an imperfect binding of guanyl nucleotides as exemplified by an increase in their dissociation rate constants and reduction of the GTPase activity of the protein. These properties of the normal and mutant rap2 proteins are compared with those of ras p21 carrying similar substitutions and are discussed in relation to the structural models proposed for ras p21. PMID- 1900291 TI - Antisera specific for rap 1 proteins distinguish between processed and nonprocessed rap 1b. AB - Polyclonal antisera were generated against synthetic peptides corresponding to distinct regions of the rap 1 protein sequences. A "rap 1-common" antiserum, prepared against an 18-amino acid segment of the rap 1a protein near the proposed GTP-binding region, reacted with both rap 1a and rap 1b recombinant proteins expressed in Escherichia coli and with two low molecular weight GTP-binding proteins of 22 and 24 kDa in unstimulated human platelets. An antiserum raised against a carboxyl-terminal peptide of rap 1b containing the putative site of post-translational processing reacted strongly with bacterial-expressed recombinant rap 1b and with a 24-kDa GTP-binding protein in platelets, but not with recombinant rap 1a or a 22-kDa GTP-binding protein. The mobility on sodium dodecyl sulfate-polyacrylamide gel electrophoresis of this rap 1b immunoreactive protein coincided with that of bacterial-expressed rap 1b and not with the faster migrating form of rap 1b that incorporates radioactivity from [3H]mevalonic acid in the insect/baculovirus system. This suggests that our rap 1b-specific antiserum recognizes only one form of rap 1b, that which has not undergone carboxyl-terminal post-translational processing. PMID- 1900292 TI - Isoprenylation of rap2 proteins in platelets and human erythroleukemia cells. AB - The covalent modification of proteins by isoprenoid derivatives of mevalonic acid was investigated in human platelets, cells that lack the ability to synthesize endogenous cholesterol, and human erythroleukemia (HEL) cells, cholesterol producing cultured cells derived from megakaryocytes. When washed platelets or HEL cells were incubated with [3H]mevalonic acid, the radiolabel was incorporated into a distinct group of proteins with molecular masses between 21,000 and 28,000. We have identified one of these proteins as a ras-related rap2 protein based on its immunoreactivity with a polyclonal antiserum raised against purified recombinant rap2b. This anti-rap2 antiserum was used for two-dimensional immunoblotting analysis and immunoprecipitation of mevalonate-labeled rap2 from platelets and HEL cells. These results suggest that rap2 may undergo a series of carboxyl-terminal modifications similar to the p21ras proteins. In addition, it is shown that non-cholesterol-producing cells are capable of incorporating isoprenyl groups into specific proteins. PMID- 1900293 TI - Carboxyl methylation of platelet rap1 proteins is stimulated by guanosine 5'-(3-O thio)triphosphate. AB - Carboxyl methylation of platelet ras-related proteins, known as rap proteins, was investigated in this study. Platelet membrane proteins of Mr 23,000 incorporated radioactivity in the presence of S-[methyl-3H]adenosylmethionine and platelet cytosol. About 97% of the radioactivity present in the Mr 23,000 proteins was liberated as volatile methanol under basic (1 M sodium hydroxide) conditions. Cycloheximide, an inhibitor of protein synthesis, inhibited incorporation of S [methyl-3H]adenosylmethionine by 25%. These results suggest that at least 75% of the radioactivity present in the Mr 23,000 proteins is due to carboxyl methylation and not due to the incorporation of S-[methyl-3H]adenosylmethionine into proteins or due to the incorporation of base-stable methyl groups into side chains of arginine, histidine, or lysine residues. Protein methylation did not occur if membranes or cytosol alone was incubated with S-[methyl 3H]adenosylmethionine. Guanosine 5'(3-O-thio)triphosphate increased methylation of the Mr 23,000 proteins in a time- and concentration-dependent manner. Acetyl farnesylcysteine, a synthetic substrate for carboxyl methyltransferases, completely blocked methylation of the Mr 23,000 membrane proteins. On the basis of one- and two-dimensional Western blots using rap-specific antisera, the Mr 23,000 methylated proteins were identified as rap1 proteins. The existence of the carboxyl-terminal CAAX motif in rap1 proteins, similar to the CAAX motif present in p21ras as well as in the yeast mating factors, leads us to suggest that methylation of rap1 proteins possibly occurs at the alpha-carboxyl-terminal cysteine. PMID- 1900294 TI - Self-association of the plasma membrane-associated clathrin assembly protein AP 2. AB - A self-association reaction involving the plasma membrane-associated clathrin assembly protein AP-2 has been detected by incubating AP-2 alone under solution conditions that would favor the assembly of complete coat structures if clathrin were present. Self-association was rapid, unaffected by nonionic detergents, readily reversible, and gave rise to sedimentable aggregates. Only the AP subtype AP-2 exhibited self-association: the structurally or functionally related assembly proteins AP-1 and AP-3 and unrelated proteins neither self-associated nor were incorporated into the AP-2 aggregate. AP-2 interactions responsible for self-association were of high affinity, with an apparent Kd of approximately 10( 8)M. By proteolytic dissection, the self-association domain was localized to the core of the molecule containing the intact 50- and 16-kDa polypeptides in association with the truncated 60-66-kDa moieties of the parent alpha/beta polypeptides. Self-association of the intact AP-2 molecule was pH-dependent, exhibiting an apparent pKa approximately 7.4. While it is unlikely that the large AP-2 aggregates formed in solution are themselves biologically relevant structures, the AP-2 interactions involved in their formation have properties consistent with their occurrence in intact cells and thus may be important in cellular functions of the plasma membrane-localized assembly protein. PMID- 1900295 TI - In vitro synthesis of G protein beta gamma dimers. AB - The guanine nucleotide-binding proteins (G proteins), which play a central role in coupling membrane-bound receptors to intracellular effectors, are heterotrimers composed of alpha, beta, and gamma subunits. The beta and gamma subunits form a functional monomer that does not appear to separate under physiological conditions. This has made it difficult to differentiate the individual roles of beta and gamma subunits in signal transduction. To characterize the individual subunits, the 36-kDa beta subunit (beta 1), brain gamma (gamma 2), and transducin gamma (gamma t) were translated in vitro in a rabbit reticulocyte lysate system. Hydrodynamic studies and tryptic proteolysis were used to compare the physical properties of the in vitro translation products with those of beta gamma dimers purified from bovine brain. The hydrodynamic studies indicate that, without gamma subunits, the beta subunits are not stable but tend to aggregate into high molecular weight complexes. When beta and gamma subunits were co-translated, stable beta gamma dimers formed that bound alpha 0 in a guanine nucleotide-dependent manner. The beta gamma dimers were less hydrophobic than those purified from bovine brain. This may reflect a lack of post-translational modification in the reticulocyte lysate or other differences between the in vitro translation products and the purified beta gamma. When beta and gamma were translated separately and then mixed, beta gamma dimers also formed. Analysis of in vitro translated beta gamma subunits will provide ways to assess the function of these subunits and to determine the structural requirements for beta gamma formation. PMID- 1900296 TI - Transcriptional regulation of the rat NAD(P)H:quinone reductase gene. Identification of regulatory elements controlling basal level expression and inducible expression by planar aromatic compounds and phenolic antioxidants. AB - We have identified two regions in the 5'-flanking sequence of the rat quinone reductase gene that contain xenobiotic responsive elements. The DNA sequence of the first region spans nucleotides -393 to -352 of the 5'-flanking region and shares sequence identity with the xenobiotic responsive element (XRE) described for the cytochrome P-450 CYPIA1 gene. The DNA sequence of the second region spans nucleotides -434 to -404 of the 5'-flanking region of the quinone reductase structural gene. When a synthetic oligonucleotide corresponding to nucleotides 434 to -404 was inserted in front of a heterologous promoter linked to the chloramphenicol acetyltransferase structural gene, an increase in basal level expression as well as responsiveness to beta-naphthoflavone and t butylhydroquinone, but not 2,3,7,8-tetrachlorodibenzo-p-dioxin, was observed. The sequence, -434 to -404, did not have any sequence identity with the XRE but shared a large degree of identity with the antioxidant responsive element recently described for the rat glutathione S-transferase Ya subunit gene (Rushmore, T. H., King, R. G., Paulson, K. E., and Pickett, C. B. (1990) Proc. Natl. Acad. Sci. U. S. A. 87, 3826-3830; Rushmore, T. H., and Pickett, C. B. (1990) J. Biol. Chem. 265, 14648-14653). These results indicate that the antioxidant responsive element can be distinguished functionally from the classical XRE and is also involved in the regulation of the quinone reductase gene by planar aromatic compounds and phenolic antioxidants. PMID- 1900297 TI - Lipid modifications of G protein subunits. Myristoylation of Go alpha increases its affinity for beta gamma. AB - Myristoylated recombinant proteins can be synthesized in Escherichia coli by concurrent expression of the enzyme myristoyl-CoA:protein N-myristoyl-transferase with its protein substrates (Duronio, R.J., Jackson-Machelski, E., Heuckeroth, R.O., Olins, P. O., Devine, C.S., Yonemoto, W., Slice, L. W., Taylor, S. S., and Gordon, J. I. (1990) Proc. Natl. Acad. Sci. U. S.A. 87, 1506-1510). Expression of the G protein subunit Go alpha in this system results in the synthesis of two forms of the protein; these were separated on a column of heptylamine-Sepharose. Purification of the more abundant form of Go alpha yielded a product that has a blocked amino terminus. Chemical analysis of the fatty acids released by acid hydrolysis of the protein revealed myristic acid. The second form of the protein was not myristoylated. Myristoylated and nonmyristoylated recombinant Go alpha were compared with brain Go alpha (which is myristoylated) for their ability to interact with G protein beta gamma subunits. The nonmyristoylated recombinant protein clearly had a reduced affinity for beta gamma, while the myristoylated recombinant protein was indistinguishable from native Go alpha in its subunit interactions. Thus, myristoylation increases the affinity of alpha subunits for beta gamma. We propose that the function of myristoylation of G protein alpha subunits is, at least in part, to facilitate formation of the heterotrimer and the localization of alpha to the plasma membrane. PMID- 1900298 TI - Mutagenesis of the human transferrin receptor: two cytoplasmic phenylalanines are required for efficient internalization and a second-site mutation is capable of reverting an internalization-defective phenotype. AB - Site-specific mutagenesis has been used to define the sequences required for efficient internalization of the human transferrin receptor. It has previously been shown that the sole cytoplasmic tyrosine, at position 20, is required for efficient internalization. When two other cytoplasmic aromatic residues, the phenylalanines at positions 13 and 23, are substituted with alanines internalization is also reduced. The phenylalanine 23 mutation decreases the internalization rate constant approximately threefold, and mutation of phenylalanine 13 decreases it by approximately twofold. The mutation at position 23 has as serious an effect on internalization as substitution with a nonaromatic amino acid for the single tyrosine. These results demonstrate the importance of several aromatic amino acids in maintaining efficient internalization of the transferrin receptor. Substitution of a tyrosine at a second site, for a serine at position 34, within the cytoplasmic domain of a transferrin receptor with a nonaromatic amino acid at position 20, results in a complete reversion of the internalization-defective phenotype. This reversion is completely dependent upon a tyrosine, as phenylalanine substituted at position 34 does not revert the internalization-defective phenotype. This result demonstrates that a tyrosine placed outside of its native context can still function in the internalization of the transferrin receptor, suggesting a flexibility in surrounding sequences required for efficient internalization. PMID- 1900299 TI - Formation and contraction of a microfilamentous shell in saponin-permeabilized platelets. AB - To study the mechanism of granule centralization in platelets, we permeabilized with saponin in either EGTA (5 mM) or calcium (1 or 10 microM). Under all conditions, platelets retained 40-50% of their total actin and greater than 70% of their actin-binding protein (ABP) but lost greater than 80% of talin and myosin to the supernatant. Thin sections of platelets permeabilized in EGTA showed a microfilament network under the residual plasma membrane and throughout the cytoplasm. Platelets permeabilized in calcium contained a microfilament shell partly separated from the residual membrane. The shell stained brightly for F actin. A less dense microfilament shell was also seen in sections of ADP stimulated intact platelets subsequently permeabilized in EGTA. In the presence of 1 mM ATP gamma S and calcium, myosin was retained (70%) and was localized by indirect immunofluorescence in bright central spots that also stained intensely for F-actin. Electron micrographs showed centralized granules surrounded by a closely packed mass of microfilaments much like the structures seen in thrombin stimulated intact platelets subsequently permeabilized in EGTA. Permeabilization in calcium, ATP, and okadaic acid, produced the same configuration of centralized granules and packed microfilaments; myosin was retained and the myosin regulatory light chain became phosphorylated. Microtubule coil disassembly before permeabilization did not inhibit granule centralization. These results suggest a possible mechanism for granule centralization in these models. The cytoskeletal network first separates from some of its connections to the plasma membrane by a calcium-dependent mechanism not involving ABP proteolysis. Phosphorylated myosin interacts with the microfilaments to contract the shell moving the granules to the platelet's center. PMID- 1900300 TI - Sec15 protein, an essential component of the exocytotic apparatus, is associated with the plasma membrane and with a soluble 19.5S particle. AB - SEC15 encodes a 116-kD protein that is essential for vesicular traffic from the Golgi apparatus to the cell surface in yeast. Although the sequence predicts a largely hydrophilic protein, a portion (23%) of Sec15p is found in association with the plasma membrane. The remainder is not associated with a membrane but is found in a 19.5S particle which is not dissociated by 0.5 M NaCl. Sec15p may attach directly to the plasma membrane since it is not found on the Golgi apparatus nor on the secretory vesicle precursors to the plasma membrane. Loss of function of most of the late-acting sec gene products does not alter the distribution of Sec15p. However, the sec8-9 mutation and to a lesser extent the sec10-2 mutation result in a shift of Sec15p to the plasma membrane, suggesting a role for these gene products in the regulation of the Sec15p membrane attachment/detachment processes. Depletion of Sec15p by repression of synthesis indicates that the plasma membrane bound pool is the most stable. During the course of these studies we have found that two activities associated with the yeast Golgi apparatus, Kex2 endopeptidase and GDPase, are in separable subcompartments. PMID- 1900301 TI - Isolation of functional, coated, endocytic vesicles. AB - Brief internalization of [125I]transferrin was used to label coated endocytic vesicles, which were then purified using a combination of 2H2O and 2H2O/Ficoll density gradients. Purification was monitored using an assay measuring fusion of endocytic organelles, so as to isolate functional vesicles. Isolated vesicles had all the properties of clathrin-coated vesicles, being enriched for the major components of clathrin coats and uncoated by either 1 M Tris-HCl or an uncoating ATPase. Nearly half of the labeled vesicles were able to participate in subsequent fusion events, as measured by the cell-free assay. Fusion was specific, requiring energy and cytosol, and being sensitive to N-ethyl maleimide. PMID- 1900302 TI - Multiple elevations of cytosolic-free Ca2+ in human neutrophils: initiation by adherence receptors of the integrin family. AB - Multiple spontaneous transient elevations of cytosolic-free calcium ([Ca2+]i) are observed in single human neutrophils during adherence. The interrelation between adherence and spontaneous [Ca2+]i transients was analyzed by simultaneous monitoring of [Ca2+]i and cell morphology. Fluorescent images of fura 2-loaded neutrophils attached to albumin-coated glass were recorded with a high sensitivity CCD camera while [Ca2+]i was assessed with a dual excitation microfluorimetry. The majority of the initially round cells studied showed changes in shape which started either before or at the same time as the onset of the [Ca2+]i transients. These data suggested that a rise in [Ca2+]i is not a prerequisite for shape change. This conclusion was confirmed by observation of movement and spreading in cells whose [Ca2+]i transients were abolished by chelation of extracellular Ca2+. Instead, our data suggest that spreading or adhesion itself initiates the [Ca2+]i activity. In keeping with this hypothesis, cytochalasin B, which prevents both cell movement and adhesion, completely inhibited generation of [Ca2+]i transients. To determine if the movement alone or adhesion alone is responsible for [Ca2+]i activity, we treated cells with antibodies against the beta chain (CD18, beta 2) or the alpha subunit (CD11b, alpha m) of the dominant leukocyte integrin (CR3). Antibody-treated cells showed normal extension of pseudopods but impaired ability to adhere. Inhibition of adhesion in this way inhibited [Ca2+]i activity. Taken together these results suggest that following sequence of events after contact of neutrophils with surfaces: (a) cell movement and shape change lead to enhanced contact of integrins with the surface; and (b) integrins-mediated adhesion generates multiple [Ca2+]i transients. The [Ca2+]i transients may then control exocytic events associated with movement and may provide a link between adherence and activation or priming of neutrophils to other stimuli. PMID- 1900304 TI - Decline of poly(ADP-ribosyl)ation during in vitro senescence in human diploid fibroblasts. AB - Poly(ADP-ribose) polymerase activity was determined at various times during the in vitro life span of two human diploid fibroblast-like cell lines of different donor ages. The cell lines differed in their ability to transfer ADP-ribose, with cells from an embryonic donor exhibiting 2 to 3 times the activity found in cells obtained from a newborn donor. The activity in both cell lines decreased by 30 60% as the cells moved through their in vitro life spans. The decline could not be attributed to increases in glycohydrolase or the leakage of polymerase from older cell preparations. Enzyme activation with DNase I indicated that similar levels of enzyme were present in both cell lines at all in vitro ages. These results indicate that although poly(ADP-ribosyl)ation is inversely related to donor age as well as in vitro age the decrease is in response to other factors which change with increasing age. PMID- 1900303 TI - Distribution and comparison of receptors for leukemia inhibitory factor on murine hemopoietic and hepatic cells. AB - Leukemia inhibitory factor (LIF) is a glycoprotein that induces the differentiation of the monocytic leukemia cell line M1 but suppresses the differentiation of totipotent embryonic stem cells. In an attempt to define the normal cellular targets for LIF, the distribution of LIF receptors within hemopoietic and hepatic tissue was analyzed by binding cells with radioiodinated LIF (125I-LIF) and subsequently carrying out autoradiography. Autoradiography demonstrated that in each hemopoietic tissue examined cells of monocyte/macrophage lineage were the primary cell type labeled with 125I-LIF. Moreover, both fetal and adult parenchymal hepatocytes displayed higher levels of labeling than either monocytes or macrophages. The number of receptors per positive cell varied from 150 for bone marrow monocytes to 2,000 for adult hepatocytes. In each case, however, binding was of high affinity, with an apparent KD of 34-100 pM, and binding was specific, since labeling was competed for by unlabeled LIF but not a range of other structurally unrelated growth and differentiation factors. It is suggested that LIF may play a role in regulating macrophage function and hepatic acute phase protein synthesis in response to infection. PMID- 1900305 TI - Bindings of the lectins Griffonia simplicifolia-1 and pokeweed mitogen mark discrete stages of myoepithelial-like differentiation of cell lines from the rat mammary gland. AB - Individual single-cell-cloned cell lines of the different rat mammary (Rama) cell types have been tested for their ability to bind the lectins Griffonia simplicifolia-1 (GS-1) and pokeweed mitogen (PWM) using fluorescent, histochemical, and radioactive assays. Myoepithelial-like cell lines isolated from neonatal rat mammary glands and from nonmetastasizing tumors strongly bind GS-1 and PWM, whereas the corresponding epithelial and fibroblastic cell lines do not. When the epithelial cell lines are grown on floating gels of polymerised rat tail collagen, the basally situated or peripheral cells are stained strongly with peroxidase-conjugated lectins, whereas the apically or luminally situated cells are unstained. The capacity of cell lines intermediate in morphology between epithelial and myoepithelial-like cells to bind to GS-1 is as follows: Rama 25 epithelial less than Rama 25-12 less than Rama 25-11 less than Rama 25-14 less than Rama 29 myoepithelial-like cells, the same order as for other markers of myoepithelial cells. Conjugated PWM, however, binds only to the myoepithelial like cell lines. Treatment of Rama 25 epithelial cells with agents that disrupt microtubules accelerates their conversion to elongated, myoepithelial-like cells in culture. The binding of cells to GS-1 is observed prior to, and that to PWM after, the major morphological change. It is suggested that the stepwise appearances of carbohydrate receptors for GS-1 and PWM mark discrete stages in the differentiation of epithelial to myoepithelial-like cells in culture, in the same way that they mark similar differentiation stages in ductal development in mammary glands of prepubertal rats. PMID- 1900306 TI - Propranolol ameliorates the development of portal-systemic shunting in a chronic murine schistosomiasis model of portal hypertension. AB - We investigated the role of early portal hypotensive pharmacotherapy in preventing the development of portal-systemic shunting in a portal hypertensive model of chronic murine schistosomiasis induced by infecting C3H mice with 60 cercariae of Schistosoma mansoni. Propranolol was administered in drinking water to 20 animals for a period of 6 wk at a dose of 10 mg.kg-1d-1, starting at 5 wk of schistosomal infection. 32 age-matched mice with chronic schistosomal infection served as controls. All animals were studied 11 wk after the infection. Compared with controls the portal pressure (10.8 +/- 0.40 mmHg) was significantly lower (P less than 0.001) in the propranolol-treated animals (7.9 +/- 0.80 mmHg). Portal-systemic shunting was decreased by 79%, from 12.2 +/- 3.34% in controls to 2.5 +/- 0.99% in the propranolol group (P less than 0.05). Portal venous inflow was reduced by 38% in the propranolol treated animals (2.50 +/- 0.73 ml/min; n = 6) compared with controls (4.00 +/- 0.34 ml/min; n = 8; P less than 0.05). The worm burden, the granulomatous reaction, the collagen content of the liver, and the serum bile acid levels were not significantly different between the two groups of animals. These results demonstrate that in chronic liver disease induced by schistosomiasis, the development of portal-systemic shunting can be decreased or prevented by the reduction of flow and pressure in the portal system. PMID- 1900307 TI - Temperature-sensitive tyrosinase associated with peripheral pigmentation in oculocutaneous albinism. AB - Several types of autosomal recessive oculocutaneous albinism (OCA) are associated with abnormal tyrosinase function and a generalized reduction in or absence of cutaneous and eye melanin. Each is thought to result from a different mutant allele at the tyrosinase locus, with the mutation producing an enzyme with little or no activity in all involved tissues. In this paper, we report a new type of OCA that results from a tyrosinase allele producing a temperature-sensitive enzyme. The proband had white hair in the warmer areas (scalp and axilla) and progressively darker hair in the cooler areas (extremities) of her body. Melanocyte and melanosome architecture were normal. Quantitative hairbulb tyrosinase (dopa oxidase) assay demonstrated a loss of activity above 35-37 degrees C. Plasma pheomelanin and urine eumelanin intermediates were reduced and correlated with hair melanin content. This is the first temperature-sensitive tyrosinase mutation to be reported in humans and is analogous to the Siamese mutation in the cat and the Himalayan mutation in the mouse. PMID- 1900309 TI - A tyrosinase gene missense mutation in temperature-sensitive type I oculocutaneous albinism. A human homologue to the Siamese cat and the Himalayan mouse. AB - Type I oculocutaneous albinism (OCA) is an autosomal recessive disorder in which deficient synthesis of melanin pigment results from abnormal activity of melanocyte tyrosinase. A novel type I OCA phenotype in which hypopigmentation is related to local body temperature is associated with a missense substitution in tyrosinase, codon 422 CGG (Arg)----CAG (Gln). This substitution results in a tyrosinase polypeptide that is temperature-sensitive. This form of type I OCA thus is homologous to the temperature-related forms of albinism seen in the Siamese cat and the Himalayan mouse. PMID- 1900308 TI - Soluble fibrin degradation products potentiate tissue plasminogen activator induced fibrinogen proteolysis. AB - Despite its affinity for fibrin, tissue plasminogen activator (t-PA) administration causes systemic fibrinogenolysis. To investigate the mechanism, t PA was incubated with plasma in the presence or absence of a fibrin clot, and the extent of fibrinogenolysis was determined by measuring B beta 1-42. In the presence of fibrin, there is a 21-fold increase in B beta 1-42 levels. The potentiation of fibrinogenolysis in the presence of fibrin is mediated by soluble fibrin degradation products because (a) the extent of t-PA induced fibrinogenolysis and clot lysis are directly related, (b) once clot lysis has been initiated, fibrinogenolysis continues even after the clot is removed, and (c) lysates of cross-linked fibrin clots potentiate t-PA-mediated fibrinogenolysis. Fibrin degradation products stimulate fibrinogenolysis by binding t-PA and plasminogen because approximately 70% of the labeled material in the clot lysates binds to both t-PA- and plasminogen-Sepharose, and only the bound fractions have potentiating activity. The binding site for t-PA and plasminogen is on the E domain because characterization of the potentiating fragments using gel filtration followed by PAGE and immunoblotting indicates that the major species is (DD)E complex, whereas minor components include high molecular weight derivatives containing the (DD)E complex and fragment E. In contrast, D-dimer is the predominant species found in the fractions that do not bind to the adsorbants, and it has no potentiating activity. Thus, soluble products of t-PA-induced lysis of cross-linked fibrin potentiate t-PA-mediated fibrinogenolysis by providing a surface for t-PA and plasminogen binding thereby promoting plasmin generation. The occurrence of this phenomenon after therapeutic thrombolysis may explain the limited clot selectivity of t-PA. PMID- 1900310 TI - High-affinity binding of interferon-gamma to a basement membrane complex (matrigel). AB - Recently it was demonstrated that growth factors are bound to the extracellular matrix, and can regulate cell behavior. Using three different types of binding assays, we have examined the interaction of interferon-gamma with a basement membrane produced by the Engelbreth-Holm-Swarm tumor. Basement membrane was found to bind interferon-gamma in both a time- and concentration-dependent manner. Equilibrium binding analysis revealed a high-affinity site with a dissociation constant of 1.5 10(-9) M and a maximum binding capacity of 1.6 10(9) sites/mm2 of basement membrane. Competition studies show that the binding is inhibited by heparan sulfate, suggesting that basement membrane-heparan sulfate proteoglycan could be the binding site. This interaction was clearly confirmed by native polyacrylamide gel electrophoresis and dot-blot analysis with purified basement membrane molecules. Furthermore, the carboxy-terminal part of the interferon gamma molecule contains an amino acid cluster, very closely related to a consensus sequence, present in more than 20 proteins known to bind sulfated glycosaminoglycans such as heparin. These data demonstrate a possible role of extracellular matrix components in storing cytokines and in modulating the cellular response to such factors. PMID- 1900312 TI - Treatment of male genital condylomatous lesions by carbon dioxide laser after failure of previous nonlaser methods. AB - Carbon dioxide laser was used to treat 119 male patients with condylomata acuminata after other treatments had failed. In 82.3% of the patients, the treatment resulted in complete disappearance of the lesions, whereas in the others two to three treatments were required. Advantages of the laser treatment are discussed. PMID- 1900311 TI - Sites of synthesis of urokinase and tissue-type plasminogen activators in the murine kidney. AB - Kidneys have long been recognized as a major source of plasminogen activators (PAs). However, neither the sites of synthesis of the enzymes nor their role in renal function have been elucidated. By the combined use of zymographies on tissue sections and in situ hybridizations, we have explored the cellular distribution of urokinase-type (u-PA) and tissue-type (t-PA) plasminogen activators and of their mRNAs in developing and adult mouse kidneys. In 17.5-d old embryos, renal tubules synthesize u-PA, while S-shaped bodies produce t-PA. In the adult kidney, u-PA is synthesized and released in urine by the epithelial cells lining the straight parts of both proximal and distal tubules. In contrast, t-PA is produced by glomerular cells and by epithelial cells lining the distal part of collecting ducts. The precise segmental distribution of PAs suggests that both enzymes may be implicated in the maintenance of tubular patency, by catalyzing extracellular proteolysis to prevent or circumvent protein precipitation. PMID- 1900314 TI - Infection control and hospital epidemiology: the formal review process. PMID- 1900313 TI - Long-lasting depression of the factor XII-dependent fibrinolytic system in patients with myocardial infarction undergoing thrombolytic therapy with recombinant tissue-type plasminogen activator: a randomized placebo-controlled study. AB - In a randomized placebo-controlled study, seven patients with acute myocardial infarction allocated to intravenous treatment with 100 mg of recombinant tissue type plasminogen activator (rt-PA) and seven patients allocated to placebo were studied during eight sampling periods before and after treatment. Seven patients with acute myocardial infarction treated intravenously with 1.5 million U of streptokinase were later studied during two sampling periods before and after treatment. The placebo group showed no significant deviations of endogenous factor XII-dependent fibrinolytic activity (p greater than 0.05). In the rt-PA group, this activity decreased significantly (p less than 0.001) after the infusion and remained depressed throughout the 1st 4 days. A significant decrease in activity (p less than 0.05) was also found in the streptokinase-treated patients. The depletion of factor XII-dependent fibrinolytic activity was not due to generation of inhibition or a depletion of factor XII, prekallikrein and plasminogen, but could be related to the proactivator of this system. It is concluded that rt-PA (and streptokinase) treatment in patients with acute myocardial infarction causes a prolonged depletion of factor XII-dependent fibrinolytic activity. This depression of endogenous fibrinolytic activity needs to be evaluated in relation to the enhanced risk of coronary reocclusion after thrombolytic therapy. PMID- 1900315 TI - Mechanisms of methicillin resistance in Staphylococcus aureus and methods for laboratory detection. AB - Three distinctly different mechanisms of methicillin resistance have been described in Staphylococcus aureus. The best-documented and probably most important mechanism is production of a unique, low affinity penicillin-binding protein, PBP 2a. Strains possessing PBP 2a are resistant to methicillin, oxacillin, and probably all other currently available beta-lactam antibiotics. Two additional mechanisms of reduced susceptibility to methicillin have been described. Borderline resistance (BORSA) to the semi-synthetic penicillins has been attributed to the hyperproduction of normal staphylococcal beta-lactamase. A third mechanism has recently been advanced that describes an intermediate level of resistance to methicillin due to production of modified, normal PBPs with reduced affinity for beta-lactams (MODSA). Little is known regarding the prevalence or clinical significance of the BORSA and MODSA strains. The most reliable in vitro susceptibility test methods for detecting MRSA (strains possessing PBP 2a) include the microdilution minimum inhibitory concentration (MIC) test (with 2% NaCl supplemented broth), the oxacillin agar screen plate test (incorporating 6 micrograms/ml oxacillin in 4% NaCl supplemented agar), and the National Committee for Clinical Laboratory Standards (NCCLS) disk diffusion test with oxacillin. All three methods use direct inoculum preparation and incubation of tests at 35 degrees C for a full 24 hours. PMID- 1900316 TI - Infection control software. PMID- 1900317 TI - Recurrence of oropharyngeal carcinoma after radiotherapy. AB - Two-hundred-and-twenty-one patients with squamous carcinoma of the oropharynx treated by irradiation are presented. The primary recurrence rate at five years in the previously untreated patients was 27%, but was dictated by neither host factors (age, sex and general condition) nor tumour factors (site, T-stage and histological grade). Pre-operative histological diagnosis had a very high sensitivity but a low specificity, indicating that false positives are common but false negatives unusual. Twenty per cent of patients with a recurrent primary tumour were untreatable. The five year survival after a primary recurrence was 31 per cent. Sixty-eight per cent of patients undergoing major surgery recovered without a major complication, and the hospital mortality rate was three per cent, due entirely to major medical catastrophes. The major complication rate in those undergoing flap repair after major resection was seven per cent. The metastatic rate in lymph nodes was 44 per cent at five years, and again this did not depend on any host or tumour factors. The survival at five years after node recurrence was a mere 19 per cent, and the length of survival was related to the primary site of the original tumour and the presence of extranodal disease. Two-thirds of patients had advanced disease (N2 and N3) when node recurrence was diagnosed and about 15 per cent were unsuitable for surgery. PMID- 1900318 TI - Extramedullary nasal plasmacytoma. AB - The literature on this rare tumour has been reviewed and three cases of nasal plasmacytoma are described. Immunohistochemistry demonstrated cytoplasmic IgA and Kappa determinants in all cases. Two patients are disease-free at the present time, the third developed an IgG-k multiple myeloma, previously not described in the literature. PMID- 1900319 TI - Control of progesterone and inhibin secretion during the luteal phase in the macaque. AB - We investigated the temporal relationship between serum concentrations of progesterone and immunoreactive inhibin after treatment with an LHRH antagonist ([N-Ac-D-Nal(2)1,D-pCl-Phe2,D-Trp3,D-hArg(Et2)6,D-Ala10++ +] -LHRH), during the mid-luteal phase in the macaque. Further, in an attempt to obtain a model of transitory suppression of luteal function, the effect of treatment with the LHRH antagonist for 1, 2 or 3 days during the mid-luteal phase on serum concentrations of progesterone and immunoreactive inhibin was compared. Differences in the pattern of decline of the two hormones were observed. Progesterone concentrations fell by 6 h after antagonist administration while inhibin was not significantly suppressed until 48 h. Treatment with three injections of LHRH antagonist caused a sustained suppression of luteal function as shown by low serum concentrations of progesterone and inhibin. Recovery of progesterone and inhibin secretion was observed in two out of six macaques treated with two injections of antagonist and in three out of six treated with a single injection. Therefore, with the regimens of LHRH antagonist which we employed this approach was not conducive to obtaining a reliable transitory suppression of luteal function. To elucidate further the gonadotrophin control of inhibin, six macaques were treated with three injections of the LHRH antagonist to induce a permanent suppression of luteal function but received concomitantly either human chorionic gonadotrophin (hCG) or human FSH daily for 5 days (n = 3 per group). FSH failed to prevent the antagonist-induced fall in progesterone and inhibin while hCG treatment completely reversed the inhibitory effects of the LHRH antagonist.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1900320 TI - Comparison of the luteolytic action of gonadotrophin-releasing hormone antagonist and cloprostenol, and the ability of human chorionic gonadotrophin and melatonin to override their luteolytic effects in the marmoset monkey. AB - The effects of the luteolytic and luteotrophic agents cloprostenol, human chorionic gonadotrophin (hCG) and melatonin on the corpus luteum have been investigated in marmoset monkeys treated with an LHRH antagonist to reduce endogenous LH secretion. This has allowed the effects of these agents to be investigated in the absence of the principal endogenous luteotrophin. Administration of the LHRH antagonist ([N-acetyl-D beta Nal1-D-pCl-Phe2-D-Phe3-D Arg6-Phe7-Arg8-D-Ala10]NH2-LHRH) or cloprostenol between days 7 and 11 after ovulation (preimplantation) resulted in luteolysis. A significant (P less than 0.05) decrease in progesterone concentrations had occurred by 4 h after administration of the LHRH antagonist and was indeed preceded by a fall in LH concentrations. Coadministration of hCG with the LHRH antagonist prevented the fall in progesterone. In contrast, administration of cloprostenol resulted in an immediate fall in progesterone concentrations, to less than half the initial level within 1 h, and co-administration with hCG did not prevent the fall. Administration of hCG stimulated progesterone production when given 8 h after the LHRH antagonist but not after 24 h. Cloprostenol prevented the stimulation by hCG. Co-administration of melatonin with the LHRH antagonist did not prevent the decrease in progesterone concentrations. Melatonin was also not effective in preventing the fall in progesterone induced by cloprostenol. However, co administration of melatonin and cloprostenol between days 17 and 21 after ovulation (post-implantation) significantly (P less than 0.05) delayed the fall in progesterone seen with cloprostenol alone. These results suggest that while the LHRH antagonist and cloprostenol have different sites of action their effect is similar at the corpus luteum, that is in depriving the corpus luteum of luteotrophic support. The results also suggest that melatonin may be able to influence the luteolytic action of cloprostenol but that its effect varies with the stage of the cycle. The physiological role for such an action, if any, remains unknown. PMID- 1900321 TI - Pharmacokinetics of thyrotrophin-releasing hormone in patients in different thyroid states. AB - In view of recent reports suggesting that thyroid hormone control of TRH degradation occurs outside the central nervous system in animals, the effect of thyroid status on serum and tissue degradation of TRH in man was investigated. In six patients with hyperthyroidism and six patients with hypothyroidism, constant TRH infusions were carried out for determination of plasma clearance rate (PCR) and half-life of disappearance (t1/2) of TRH, with simultaneous determination of half-life of disappearance in serum in vitro (t1/2p). Using a kinetic model, this enabled the calculation of the half-life of disappearance in the extravascular tissue compartment (t1/2t). All patients were reinvestigated after they had become euthyroid. PCR, t1/2 and t1/2p were 22.1 +/- 3.4 ml/kg per min, 6.8 +/- 1.1 min and 17.3 +/- 6.7 min (means +/- S.D.) respectively in the euthyroid patients. The t1/2p was slightly but significantly prolonged during hyperthyroidism. The t1/2 was 5.6 min in the hyperthyroid patients compared with 9.4 min in the hypothyroid patients. The calculated t1/2t was 6.5 min in the euthyroid patients. In the patients with untreated hyperthyroidism, t1/2t was significantly reduced (22.7 +/- 10.7%; mean +/- S.D.), while it was considerably prolonged (41.1 +/- 24.6%) in patients with untreated hypothyroidism. The percentage reduction or prolongation of t1/2t was negatively correlated with the logarithm of the serum concentrations of thyroxine (r = 0.92) and tri iodothyronine (r = 0.91) in the untreated patients. Thus, thyroid hormones induce alterations in the pharmacokinetics of TRH. This may partly be due to induction by thyroid hormones of membrane-bound pyroglutamyl aminopeptidase. PMID- 1900323 TI - Capnography for detection of endobronchial migration of an endotracheal tube. AB - A patient is described in whom migration of an endotracheal tube into the right main bronchus was suspected when end-tidal carbon dioxide suddenly decreased from 28 to 22 mm Hg. Acute changes with migration of the endotracheal tube into the main bronchus were also studied in an animal experimental model. End-tidal carbon dioxide decreased and tracheal (inflation) pressure increased, with no change in tidal volume. Arterial blood gases showed time-dependent decreases in pH and oxygen tension and an increase in carbon dioxide tension. PMID- 1900322 TI - Patterns of plasma sex hormone-binding globulin, thyroxine and thyroxine-binding globulin in relation to reproductive state and hibernation in female little brown bats. AB - A sex hormone-binding globulin (SHBG), which bound both oestradiol and dihydrotestosterone, was studied in the plasma of adult female little brown bats throughout the annual reproductive cycle. This protein was present at low baseline levels from September to May inclusive, months which correspond to the periods of hibernation, ovulation and early pregnancy. During the second half of pregnancy in June, SHBG levels increased 15- to 30-fold and remained increased throughout lactation and anoestrus/prooestrus (July-August). Although SHBG was increased during late pregnancy, the fact that levels were also high during and after lactation indicates that this protein is not specific to pregnancy. Plasma concentrations of thyroxine (T4) and the percentage binding of T4 to thyroxine binding globulin (TBG) also showed marked seasonal variations, with T4 levels exhibiting a biphasic seasonal pattern. A major peak in plasma concentrations of T4 occurred around the time of spring arousal from hibernation and subsequent ovulation, while a second peak of lesser magnitude was measured in August, corresponding to the time of pro-oestrus and the onset of mating. The percentage binding of T4 by TBG was increased during the summer months in parallel with the increase in SHBG concentrations. Electrophoretic analysis of plasma T4 binding revealed a single peak of TBG activity throughout most of the year; however, during the early lactational period TBG was resolved as a double peak, suggesting the presence of a molecular variant during this reproductive stage. PMID- 1900324 TI - Reduction of fresh gas flow requirements by a circle-modified bain breathing circuit. AB - We modified a Bain circuit by placing the circuit into the Y piece of a standard carbon dioxide absorber circle, connecting the fresh gas hose on the anesthetic machine to the Bain's fresh gas inlet, and occluding the circle's fresh gas inlet. This circle-modified Bain breathing circuit was studied to evaluate whether it reduces fresh gas flow requirements. The Bain and modified Bain steady states were analyzed by mechanical and computer modeling. The mechanical model consisted of an artificial lung ventilated to steady state. Carbon dioxide was measured with capnography. Computer modeling was by compartmental analysis calculated with spread-sheet software. Steady-state solutions were obtained by numeric analysis. The circle-modified Bain greatly reduced retention of carbon dioxide. For example, with 1-liter tidal volumes, 10-liter minute volumes (10 breaths per minute), and a 2.1 L/min fresh gas flow, the steady-state end-tidal carbon dioxide values of the Bain and modified Bain were 9.3 and 4.6%, respectively, in the physical model (carbon dioxide inflow of 230 ml/min). Results from the mechanical model helped validate the computer model. PMID- 1900325 TI - Ionic influences on the prolonged depolarization of turtle cones in situ. AB - 1. The effects of ion channel blockers and ion substitutions on the prolonged depolarization of cones in the retina of the turtle (Pseudemys scripta elegans) were studied by intracellular recording. 2. The results of current injection experiments indicate that the prolonged depolarization is regenerative and accompanied by a reduction in the cone's input resistance. 3. The addition of cobalt (5-10 mM) or the removal of extracellular calcium suppressed the prolonged depolarization. Raising extracellular calcium or adding strontium (10 mM) lowered the threshold and increased the duration of the response. 4. Unlike the feedback spikes of turtle cones studied by Piccolino and Gerschenfeld, the prolonged depolarization was not blocked by the organic calcium channel blocker, D600. 5. Adding a calcium chelator, ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N' tetraacetic acid (EGTA), to the electrolyte caused a progressive shortening of the prolonged depolarization until it was ultimately abolished. 6. Lowering extracellular sodium or use of the potassium channel blockers tetraethylammonium (TEA) and 4-aminopyridine (4-AP) had little effect on the prolonged depolarization. 7. Removing chloride from the superfusate induced a significant enhancement of the prolonged depolarization. In normal superfusate, the response tended to be of larger amplitude when recorded with electrodes containing chloride [1.5 M KCl + 1.5 M potassium acetate (KA)] rather than KA or potassium methylsulfate (KM) alone. 8. The results suggest that the prolonged depolarization is initiated by the regenerative activation of voltage-sensitive calcium channels and sustained by a calcium-dependent chloride efflux. The present findings are also discussed in relation to the functional significance of the prolonged depolarization and mechanisms for the surround antagonism of cones in situ. PMID- 1900326 TI - Financial techniques for evaluating equipment acquisitions. AB - The author explains various financial techniques that can be used to evaluate equipment acquisitions. She also introduces the concept of the time value of money and explains how incorporating this concept into the analysis can provide nurse executives with a better perspective of the factors involved in committing organizational funds to long-term capital purchases. PMID- 1900327 TI - The university hospital nurse extender model. Part III, Program evaluation. AB - This article is the third part of a four-part series on The University Hospital Nurse Extender Model Using Patient Care Technicians. Part I provided the overview and conceptual framework for the model. Part II described each phase of the implementation process. This article presents the results of a 1-year evaluation of the impact of the model on nursing practice and satisfaction, and the cost of using the model. Part IV will present the lessons learned from this attempt to reconfigure patient care delivery. PMID- 1900328 TI - Documentation. A focus for cost savings. AB - Documentation typically is an area that can be streamlined, thereby saving nursing time and money. The authors' nursing division created a combination intervention record and nursing progress notes form for a 24-hour period. The results yielded a savings of 90 minutes of RN time in a 24-hours period, a 36% reduction in charting time, and an annual cost savings of $437,000. PMID- 1900329 TI - Long-term care needs of hospitalized persons with AIDS: a prospective cohort study. AB - OBJECTIVE: As the treatment for HIV infection has improved, AIDS has become a chronic disease, and the demand for long-term care has increased. The authors studied a cohort of hospitalized persons with AIDS to determine the proportion and characteristics of AIDS patients who could appropriately be cared for in long term care facilities with skilled nursing. DESIGN: Prospective cohort study. SETTING: Medical wards of five Seattle tertiary care hospitals. PARTICIPANTS: 120 consecutive hospitalized persons with AIDS and their primary care physicians, nurses, and social workers. MEASUREMENTS AND MAIN RESULTS: Appropriateness for long-term care was determined by the patients' physicians, nurses, and social workers. Persons with AIDS who were appropriate for long-term care constituted 32% of the cohort (38 of 120), accounting for 35% of hospital days (11 of these 38 were discharged to long-term care facilities). Four admission characteristics were independently related to appropriateness: impaired activities of daily living, diagnosis of central nervous system illness or poor cognition, living alone, and weight loss. A discriminant function correctly classified over 80% of patients for appropriateness and was developed into a predictive index for planning patient care (sensitivity = 0.74, specificity = 0.85). CONCLUSIONS: The authors conclude that one-third of hospitalized persons with AIDS may be appropriate for care in long-term care settings, accounting for one-third of the days AIDS patients currently spend in hospitals. These patients can be identified early in hospital stays using a simple predictive index at the bedside. PMID- 1900331 TI - Diagnosis clusters in ambulatory medicine. PMID- 1900330 TI - A patient-based system for describing ambulatory medicine practices using diagnosis clusters. AB - OBJECTIVE: To develop a patient-based classification system to describe the clinical content of ambulatory medicine practices. DESIGN: A system of 100 diagnosis clusters was developed based on retrospective review of computerized problem lists of patients from a university practice, and then applied to the problem lists of patients in a community practice. Chart review of a 5% random sample (n = 184) of university practice patients who had problem lists was carried out to assess the accuracy of the computerized problem lists. SETTING: A university ambulatory medicine practice and a community ambulatory medicine practice. PATIENTS/PARTICIPANTS: For the same one-year period, all 4,490 patients seen in the university practice and all 1,294 patients seen two or more times in the community practice. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of the 27,634 problems listed for university patients and the 5,648 problems listed for community patients, 22,629 (82%) and 4,924 (87%), respectively, were assigned to diagnosis clusters. For the university and community practices, the mean numbers of problems per patient were 6.1 (SD 5.4) and 4.4 (SD 3.7), and the mean numbers of diagnosis clusters per patient were 4.5 (SD 3.7) and 3.6 (SD 3.0), respectively. Among the ten most common diagnosis clusters in both practices were HYPERTENSION, SYMPTOM OR SIGN, OBESITY, and DIABETES. Only 18% (SD 3%) of patient problem lists in the university practice omitted one or more chronic, important medical problems (e.g., hypertension, dementia, COPD). CONCLUSIONS: This system of diagnosis clusters effectively and efficiently described the clinical content of two types of internal medicine practices, and has important applications in medical education, epidemiology, clinical and health services research, and public policy. PMID- 1900332 TI - Immune complex transfer enzyme immunoassay for (anti-human T-cell leukemia virus type I) IgG in serum using a synthetic peptide, Env gp46(188-209), as antigen. AB - An immune complex transfer enzyme immunoassay for (anti-human T-cell leukemia virus type I) IgG (anti-HTLV-I IgG) in serum using a chemically and safely synthesized peptide, env gp46(188-209), is described. Anti-HTLV-I IgG in test serum, which had been incubated with excess of inactive beta-D-galactosidase to eliminate interference by anti-beta-D-galactosidase antibodies, was reacted simultaneously with dinitrophenyl bovine serum albumin-env gp46(188-209) conjugate and env gp46(188-209)-beta-D-galactosidase conjugate. The complex formed of the three components was trapped onto polystyrene balls coated with affinity-purified (anti-dinitrophenyl group) IgG. After washing to eliminate nonspecific IgG in the test serum and excess of the beta-D-galactosidase conjugate, the complex was eluted from the polystyrene balls with dinitrophenyl-L lysine and transferred to polystyrene balls coated with affinity-purified (anti human IgG gamma-chain) IgG. beta-D-Galactosidase activity bound to the (anti human IgG gamma-chain) IgG-coated polystyrene balls was assayed by fluorometry. This assay was sensitive and detected anti-HTLV-I IgG in serum samples which were negative by the conventional enzyme immunoassay and Western blotting. And the specificity of this assay was confirmed by preincubation of test serum with excess of env gp46(188-209). However, some disadvantages were also noted. PMID- 1900333 TI - Use of recombinant human interferon gamma to enhance neutrophil chemotactic responses in Job syndrome of hyperimmunoglobulinemia E and recurrent infections. AB - Recombinant human interferon gamma enhances neutrophil respiratory burst and bactericidal activity in patients with chronic granulomatous disease. Mononuclear leukocytes of patients with the hyperimmunoglobulinemia E syndrome (Job syndrome) produce low or undetectable levels of this lymphokine. For these reasons we have restudied neutrophil chemotaxis in a group of our patients with the syndrome and determined the effect of recombinant human interferon gamma on the responses. Each of the patients had neutrophil chemotactic responses ranging from 22% to 55% of simultaneous control values (p less than 0.001). After incubation with interferon gamma, a significant improvement in chemotactic responsiveness was observed in the neutrophils of each of the patients (mean 301% of baseline chemotaxis; p less than 0.008). These data suggest the need for a double-blind, placebo-controlled trial of interferon gamma in a larger group of patients with the syndrome of hyperimmunoglobulinemia E and recurrent infections. PMID- 1900334 TI - Tissue plasminogen activator for the treatment of thromboembolism in infants and children. AB - We report our experience with the use of tissue plasminogen activator to treat 12 infants and children with various thromboembolic states after conventional thrombolytic agents had failed. The dosage range was between 0.1 to 0.5 mg/kg per hour. Complete clot dissolution occurred in seven cases after 2 hours to 3 days of therapy. Partial clot dissolution and clinical improvement were noted in another four patients. Bleeding complications were noted in 6 of the 12 patients and included bruising, oozing from various venipuncture sites, and bleeding; these complications were controlled by clinically available means. In all cases with bleeding the dose rate was in the higher range (0.46 to 0.50 mg/kg per hour). In one patient, restlessness, agitation, and screaming were noted during administration of tissue plasminogen activator and when it was reinstituted. We conclude that tissue plasminogen activator is effective in inducing clot lysis in children. Because the effective dose appears to overlap with those causing bleeding, we recommend that a dose of 0.1 mg/kg per hour be started and increased gradually if clot dissolution does not occur, with close monitoring for bleeding. PMID- 1900336 TI - Weak data mire colon screening debate. PMID- 1900335 TI - Transdermal glyceryl trinitrate to allow peripheral total parenteral nutrition: a double-blind placebo controlled feasibility study. AB - Seventy-two consecutive patients requiring total parenteral nutrition (TPN) were randomized to two groups. Group A received daily a peripheral intravenous regimen which provided 10 g nitrogen and 1400 non-nitrogen kcal (5.9 MJ). Group B received daily a peripheral intravenous regimen which delivered 9.4 g nitrogen and 1900 non-nitrogen kcal (8.0 MJ). Each group was further randomized to receive a self-adhesive patch of transdermal glyceryl trinitrate (GTN) or an identical placebo. Infusion survival was the main end-point. For group A, the median time of infusion survival was 74 h (range: 58-100) in the control group compared with 108 h (range: 68-156) in the group that received transdermal GTN (P less than 0.001). For group B, the median infusion survival was 67 h (range: 46-92) in the control group compared with 103 h (range: 66-151) in the treatment group (P less than 0.001). TPN is feasible via peripheral veins and the incidence of infusion failure can be effectively reduced by transdermal GTN. PMID- 1900337 TI - Filtration coefficient in isolated preserved and reperfused canine lung. AB - The filtration coefficient (Kf) in Starling's equation for fluid exchange was estimated in isolated reperfused canine lobes to evaluate the effect of ischemia reperfusion injury on alveolar-capillary permeability quantitatively and to determine the inhibitory effects of a high dose of methylprednisolone (MPS) or dimethylthiourea (DMTU), a potent hydroxyl radical scavenger, on this injury. We reperfused isolated canine left lower lobes (LLLs) with blood at a constant flow after 3 hr of warm (38 degrees C) or cold (4 degrees C) ischemia and measured Kf after 1 hr of reperfusion. The mean value of Kf (+/- 1 SD) in the cold ischemic lobes (COLD, n = 7), 0.13 +/- 0.04 g.min-1.cmH2O-1.100 g-1, was not different from that in the control nonischemic lobes (CONT, n = 6), 0.10 +/- 0.04 g.min 1.cmH2O-1.100 g-1. In contrast, the mean value of the Kf in the warm ischemic lobes (WARM, n = 7), 0.38 +/- 0.17 g.min-1.cmH2O-1.100 g-1, was significantly (P less than 0.001) higher than in CONT.MPS (30 mg/Kg) or DMTU (0.75 g/kg) administered before isolation of LLL and before reperfusion reduced the increase in Kf in warm ischemic lobes to 0.19 +/- 0.09 and 0.19 +/- 0.05 g.min-1.cmH2O 1.100 g-1, respectively (P less than 0.005 WARM vs MPS, and P less than 0.01 WARM vs DMTU). MPS and DMTU also attenuated the impairment of gas exchange. We conclude that (1) reperfusion after 3 hr of warm ischemia increases Kf but after cold ischemia does not, and (2) MPS and DMTU prevent the increase in Kf.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1900339 TI - Intestinal diamine oxidase levels reflect ischemic injury. AB - Mucosal diamine oxidase (DAO) decreases during intestinal ischemia and may be a useful marker of intestinal ischemic injury. Tissue DAO activity and histologic changes were studied in intestinal segments taken from the midpoint of the small intestine before and 2, 4, and 24 hr after manipulation of the intestinal blood supply in 24 mongrel dogs. Intestinal DAO activity decreased significantly (17 +/ 21% of control value) 24 hr after SMA ligation and was associated with abnormal histology (histology score 7.8 +/- 2.9 at 24 hr vs 0.3 +/- 0.5 at 0 hr). SMA occlusion for 2 hr resulted in a significant decrease in DAO activity (45 +/- 36% of control value) 4 hr after manipulation which returned to normal at 24 hr, as did the histologic injury. Ligation of both the mesenteric arteries and veins resulted in a more rapid decrease in DAO activity. Decreased DAO activity correlated with the extent of histologic injury. Intestinal ischemia is associated with decreased intestinal DAO activity, which is influenced by the mechanism and duration of intestinal ischemia. PMID- 1900338 TI - The effect of intestinal autotransplantation on serum diamine oxidase activity. AB - Circulating levels of diamine oxidase (DAO), a mucosal enzyme found primarily in the small intestine, have been shown to reflect intestinal mucosal damage in a variety of disease states. Our aim was to assess the usefulness of both basal and postheparin DAO activity as a marker of intestinal allograft rejection by studying the influence of the nonrejection effects of intestinal transplantation on these activities. This separation of the immunological from all other effects of transplantation was achieved by studying 11 dogs who had undergone autotransplantation of the small intestine and 11 unoperated controls. Basal serum DAO activity increased during the first 3 postoperative days following autotransplantation (20.5 +/- 0.7 units/ml on Day 3 versus 6.9 +/- 4.1 units/ml preoperatively, P less than 0.05) but thereafter returned to control levels at 1 month and remained so for more than 18 months. Postheparin DAO activity was similar in both groups with a maximum increase between 15 and 60 min following heparin administration. There was no correlation between maximal DAO activity and time since operation in the transplant group. Intestinal DAO activity was similar to unoperated animals 18 months after autotransplantation. These findings suggest that postheparin serum diamine oxidase activity is not influenced by autotransplantation and thus, is a potential marker of graft rejection following intestinal allotransplantation. PMID- 1900340 TI - [Medical decision theory is more and more established. Critical scrutinizing with unconventional methods]. PMID- 1900341 TI - [Occurrence of chronic granulomatous disease must be surveyed--new treatment exists]. PMID- 1900342 TI - Effects of pravastatin (CS-514) on biliary lipid metabolism in patients with hyperlipidemia. AB - Pravastatin was administered to 20 patients with hyperlipidemia type IIa and IIb, for a period of 8 to 16 weeks at a daily dose of 10 to 20 mg, to investigate the effects on serum and biliary lipids. At the end of the treatment with pravastatin, the serum cholesterol level was significantly reduced, by 20%, compared with the control level. On the other hand, no significant differences were observed in serum high-density lipoprotein (HDL) cholesterol and triglyceride levels. Additionally, the administration of pravastatin did not change mode % compositions of biliary lipids, such as cholesterol, phospholipids, and total bile acids, as well as individual biliary bile acids. Consequently, there was not any significant change of the cholesterol saturation index. Based on the above results, our findings suggest that, for the treatment of hyperlipidemia, pravastatin is a highly effective cholesterol-lowering drug that does not affect biliary lipid metabolism. PMID- 1900343 TI - Impaired activation of skeletal muscle glycogen synthase in non-insulin-dependent diabetes mellitus is unrelated to the degree of obesity. AB - Twenty-five newly presenting, untreated, white, non-insulin-dependent diabetic (NIDDM) subjects were studied within 72 hours of diagnosis. They were allocated to three groups according to their body mass index [BMI] (lean BMI less than 25.0, n = 9; overweight BMI 25.0 to 30.0, n = 6; obese BMI greater than .30.0 kg/m2, n = 10). All three groups exhibited equivalent hyperglycemia. Eleven normal control subjects were also studied. The degree of activation of skeletal muscle glycogen synthase (GS) was used as an intracellular marker of insulin action, before and during a 240-minute insulin infusion (100 mU/kg/h). Fractional GS activity did not increase in the lean (change, -0.9 +/- 3.3%), the overweight (-1.9 +/- 2.7%), or the obese (+2.2 +/- 1.6%) NIDDM subjects during the insulin infusion and was markedly decreased compared with the control subjects (change, +14.6 +/- 2.4%, all P less than .001). Glucose requirement was also significantly decreased in all three NIDDM groups (103 +/- 23 v 81 +/- 14 v 53 +/- 14 mg/m2/min, respectively) compared with the control subjects (319 +/- 18 mg/m2/min, all P less than .001). There was a significant negative correlation with BMI (r = -.51, P less than .01), but the difference in glucose requirement between the lean and obese NIDDM groups was not significant. Muscle GS activity at the end of the euglycemic clamp correlated with glucose requirement (r = .53, P less than .001), and a similar correlation was observed between the insulin induced change in muscle GS activity from basal and glucose requirement (r = .47, P less than .005).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1900344 TI - Cleaning and disinfection of endoscopes: have there been recent improvements? AB - OBJECTIVE: to determine if there have been improvements in the manner in which endoscopes are being cleaned and disinfected since our previous study in 1987. In that study of 123 hospitals, in only 45% of institutions did cleaning and disinfection appear to be satisfactory. DESIGN: One hundred and twenty-two questionnaires were sent to the endoscopy charge nurse of the hospitals identifiable from our previous study. To ensure the collection of complete information from these hospitals, in those from whom a written reply was not received, the information was obtained by persistent telephone contact. The criteria used to assess adequate cleaning and disinfection were the same as in our previous study. These were based on recommendations of learned bodies and the literature. SETTING: A complete cross section of hospitals from all States and Territories in Australia was surveyed. These were both public and private, primary care to tertiary referral, teaching and non-teaching, city and country. MAIN OUTCOME: One hundred and twenty-three replies were obtained from the 122 hospitals surveyed. In 75% cleaning and disinfection of endoscopes appeared to be satisfactory. Adequate cleaning procedures were noted in 77% compared with 60% in the 1987 survey. The use of appropriate disinfection increased to 94% from 62% previously. CONCLUSION: We found that since 1987 there had been a considerable improvement in the cleaning and disinfection of endoscopes in the hospitals surveyed. PMID- 1900345 TI - A field study of bacterial growth in continuous feedings in a neonatal intensive care unit. PMID- 1900346 TI - Structural genes of glutamate 1-semialdehyde aminotransferase for porphyrin synthesis in a cyanobacterium and Escherichia coli. AB - In bacteria 5-aminolevulinate, the universal precursor in the biosynthesis of the porphyrin nucleus of hemes, chlorophylls and bilins is synthesised by two different pathways: in non-sulphur purple bacteria (Rhodobacter) or Rhizobium 5 aminolevulinate synthase condenses glycine and succinyl-CoA into 5 aminolevulinate as is the case in mammalian cells and yeast. In cyanobacteria, green and purple sulphur bacteria, as in chloroplasts of higher plants and algae a three step pathway converts glutamate into 5-aminolevulinate. The last step is the conversion of glutamate 1-semialdehyde into 5-aminolevulinate. Using a cDNA clone encoding glutamate 1-semialdehyde aminotransferase from barley, genes for this enzyme were cloned from Synechococcus PCC6301 and Escherichia coli and sequenced. The popC gene of E. coli, previously considered to encode 5 aminolevulinate synthase, appears to be a structural gene for glutamate 1 semialdehyde aminotransferase. Domains with identical amino acid sequences comprise 48% of the primary structure of the barley, cyanobacterial and putative E. coli glutamate 1-semialdehyde aminotransferases. The cyanobacterial and barley enzymes share 72% identical residues. The peptide containing a likely pyridoxamine phosphate binding lysine is conserved in all three protein sequences. PMID- 1900347 TI - Calcium-dependent protease of the cyanobacterium Anabaena: molecular cloning and expression of the gene in Escherichia coli, sequencing and site-directed mutagenesis. AB - It has been suggested that a calcium-dependent intracellular protease of the cyanobacterium, Anabaena sp., participates in the differentiation of heterocysts, cells that are specialized for fixation of N2. Clones of the structural gene (designated prcA) for this protease from Anabaena variabilis strain ATCC 29413 and Anabaena sp. strain PCC 7120 were identified via their expression in Escherichia coli. The prcA gene from A. variabilis was sequenced. The genes of both strains, mutated by insertion of a drug resistance cassette, were returned to these same strains of Anabaena on suicide plasmids. The method of sacB mediated positive selection for double recombinants was used to achieve replacement of the wild-type prcA genes by the mutated forms. The resulting mutants, which lacked Ca2(+)-dependent protease activity, were not impaired in heterocyst formation and grew on N2 as sole nitrogen source. PMID- 1900348 TI - Expression of the penDE gene of Penicillium chrysogenum encoding isopenicillin N acyltransferase in Cephalosporium acremonium: production of benzylpenicillin by the transformants. AB - No DNA sequence homologous to the penDE gene of Penicillium chrysogenum was found in the genome of three different strains of Cephalosporium acremonium. The pcbC penDE gene cluster of P. chrysogenum complemented the isopenicillin N synthase deficiency of C. acremonium mutant N2 and resulted in the production of penicillin, in addition to cephalosporin, in cultures supplemented with phenylacetic acid. The penicillin formed was identified as benzylpenicillin by HPLC and NMR studies. The penDE gene of P. chrysogenum is expressed in C. acremonium forming a transcript of 1.15 kb. The transcript is processed and translated in C. acremonium resulting in the formation of acyl CoA: isopenicillin N acyl transferase. When the penDE gene was introduced into a cephalosporin producing strain, the total titre of beta-lactam antibiotics comprised distinct proportions of penicillin and cephalosporin in different transformants. Analysis of the hybridization patterns of the DNA of C. acremonium transformed with the pcbC or penDE genes indicated that integration occurs by non-homologous recombination. PMID- 1900349 TI - Cytogenetical analysis of the 2B3-4-2B11 region of the X chromosome of Drosophila melanogaster. VII. Influence of the ecs locus on female fertility. AB - Of 13 ecs mutations, which affect female fertility, as revealed by complementation analysis, 7 are chromosome rearrangements involving the br complementation group. The other six show no cytologically detectable rearrangements and behave as completely or partially noncomplementing ecs alleles. All viable combinations of these 13 mutations were characterized by partial or complete female sterility. Viable heterozygotes carrying any of these mutations and the rearrangements Df(1)sta, T(1;3)sta, Df(1)St490, previously localized distal to the ecs locus, were also sterile. Using deletions and an electrophoretic mobility variant from the Staket strain, a minor chorion gene S70 has been mapped. It had been thought this gene was located in the 2B3-5 region, and corresponded to the ecs locus. However, in the present study, this gene was shown to map in the region removed by Df(1)sta (1E1-2-2B3-4) but outside that removed by Df(1)At127 (1E1-2-2A1-2), i.e. within the 2A1-2-2B3-4 region which is distal to the ecs locus. Rearrangements and point mutations at the ecs locus that result in female sterility had no effect on synthesis of the chorion protein s70. It may therefore be suggested that the chorion protein gene is not functionally associated with the ecs locus and that sterility is caused not by disruptions of the chorion protein gene but by lesions in the ecs gene itself. Thus, an ecs product, which controls cell sensitivity to ecdysterone is also necessary for female fertility.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1900350 TI - Inhibitory effects of coffee on the genotoxicity of carcinogens in mice. AB - The mouse bone marrow micronucleus test was carried out to evaluate the possible inhibitory effects of 3 doses (125, 250 and 500 mg/kg) of standard instant coffee on the in vivo genotoxicity of 7,12-dimethylbenz[a]anthracene (DMBA), benzo[a]pyrene (BP), aflatoxin B1 (AFB1) and urethane (UR). Coffee was orally administered twice, 2 and 20 h before the carcinogens were injected intraperitoneally. From the results obtained, it was evident that the administration of 250 and 500 mg coffee/kg body weight could significantly inhibit the in vivo genotoxicity of these carcinogens. A linear dose response was observed for the inhibitory effect of coffee. Furthermore, inhibition of genotoxicity by coffee was observed in bone marrow cells which were sampled at 6 h intervals (48, 54, 60, 66 and 72 h) from the time of peak induction of micronuclei by DMBA. PMID- 1900351 TI - Use of the cytokinesis-block micronucleus method in mouse splenocytes. AB - Mouse splenocytes have been used in the cytokinesis-block method for the evaluation of micronuclei induced by mutagenic agents in vitro as well as in vivo. Stimulation with concanavalin A for 48 h followed by 16-24-h treatment with 5 micrograms/ml cytochalasin B was found to be an optimum condition to obtain micronuclei in the binucleated splenocytes after the cells were cultured in vitro. Under the above conditions splenocytes from mice pretreated with a single i.p. injection of cyclophosphamide gave a significant increase in micronucleus production. This increase was dependent on the dose of cyclophosphamide (r = 0.99). A dose of 50 mg/kg resulted in 22% of the binucleated cells producing micronuclei, more than 20 times the level in the untreated control. The increase was also dependent on the time of cyclophosphamide injection before removal of the spleen. A duration of 4-8 h after cyclophosphamide injection gave rather sharp optimum values for the production of micronuclei. When splenocytes from non treated mice were treated with mitomycin C together with cytochalasin B in the above in vitro condition, there was a significant increase in micronucleus production in the binucleated cells. It was also dependent on the dose of mitomycin C (r = 0.975) and a dose of 0.5 micrograms/ml resulted in a more than 20-fold increase over the untreated control. Thus, the use of mouse splenocytes in the cytokinesis-block micronucleus assay was shown to be sensitive enough for testing mutagenic agents in vivo as well as in vitro. PMID- 1900352 TI - Cell biology. Membrane traffic COPs. PMID- 1900353 TI - Odorant signal termination by olfactory UDP glucuronosyl transferase. AB - The onset of olfactory transduction has been extensively studied, but considerably less is known about the molecular basis of olfactory signal termination. It has been suggested that the highly active cytochrome P450 monooxygenases of olfactory neuroepithelium are termination enzymes, a notion supported by the identification and molecular cloning of olfactory-specific cytochrome P450s (refs. 13-16). But as reactions catalysed by cytochrome P450 (refs 17, 18) often do not significantly alter volatility, lipophilicity or odour properties, cytochrome P450 may not be solely responsible for olfactory signal termination. In liver and other tissues, drug hydroxylation by cytochrome P450 is frequently followed by phase II biotransformation, for example by UDP glucuronosyl transferase (UGT), resulting in a major change of solubility and chemical properties. We report here the molecular cloning and expression of an olfactory-specific UGT. The olfactory enzyme, but not the one in liver microsomes, shows preference for odorants over standard UGT substrates. Furthermore, glucuronic acid conjugation abolishes the ability of odorants to stimulate olfactory adenylyl cyclase. This, together with the known broad spectrum of drug-detoxification enzymes, supports a role for olfactory UGT in terminating diverse odorant signals. PMID- 1900354 TI - Regulation of AP-1/DNA complex formation in vitro. AB - The level of AP-1 DNA-binding activity exhibited in vitro by unfractionated extracts of Hela nuclei can be stimulated by a low molecular weight fraction from rabbit reticulocyte lysate. Stimulation also requires a heat labile component of the nuclear extract, probably a protein. Stimulated and unstimulated extracts with high and low AP-1 DNA-binding activities contain the same levels of proteins reactive with antisera against Jun and Fos, proteins which are shown to be involved in the AP-1/DNA complexes detected in vitro. The low molecular weight fraction from reticulocyte lysate can be substituted by the reducing agent dithiothreitol (DTT) in the stimulation reaction and conversely oxidised glutathione greatly reduces formation of AP-1/DNA complexes. The binding activities of transcription factors SP-1, NF-1 and CBP are unaffected by DTT or oxidised glutathione. These observations, taken together, suggest that the efficiency with which pre-existing Fos and Jun proteins can bind an AP-1 target sequence in vitro can be controlled by a nuclear activity which is sensitive to oxidation/reduction and that this control mechanism is specific for AP-1. PMID- 1900355 TI - Inhibition of PDGF-induced c-jun and c-fos expression by a tyrosine protein kinase inhibitor. AB - The expression of the proto-oncogenes c-fos, c-jun, jun B and jun D was monitored in quiescent C3H10T1/2 fibroblasts after stimulation with PDGF. The mRNA level of c-fos, c-jun and jun B, but not of jun D, was stimulated by PDGF. The inductions were abolished when genistein, a specific tyrosine protein kinase inhibitor, was added concomitantly with PDGF, a condition in which DNA synthesis is known to be inhibited. As already shown previously, treatment with PDGF and genistein for 4h followed by the replacement with fresh medium induces the progression of the cells through the G1 phase of their growth-division cycle, without phospholipase C activation. The removal of PDGF and genistein was accompanied by an important increase in c-fos, c-jun and jun B mRNA expression, which correlated with the entrance of cells into G1 phase. Thus, the proto-oncogene expressions induced by PDGF are also obtained in the absence of phospholipase C activation. This result also suggests that the mRNA levels of c-jun, jun B and to a lesser degree c-fos are positively regulated by tyrosine protein kinase activity, whereas jun D is negatively regulated. PMID- 1900357 TI - A potential role for c-jun in cell cycle progression through late G1 and S. AB - When the level of c-jun mRNA was analyzed in WI-38 human fibroblasts exciting short- and long-term quiescence, two peaks of c-jun mRNA accumulation were found. The first occurred one hour after stimulation and lasted three to five hours, whereas the second occurred at the G1/S border and was coupled to the time of entry to S phase rather than to the time of stimulation. The early peak is well documented and in agreement with the proposed role of c-Jun/AP-1 in mediating cellular responses to receptor-generated signals. The later peak, however, has not been previously reported. Additional follow-up studies showed that late G1/S expression was not solely a phenomenon of cells existing a quiescent state, nor was it restricted only to human cells. Gel retardation studies confirmed that there is AP-1 specific DNA binding activity in nuclear extracts isolated in late G1 and S phase, and that this AP-1 binding activity is due to the presence of Jun protein. An anti-Fos antibody was able to significantly decrease AB-1 binding activity in early G1 extracts, but had no effect on extracts isolated in late G1 and S phase, indicating that the complexes observed in late G1 and S phase are clearly different from those seen in early G1. These studies are among the first to suggest a functional dissociation of c-Jun from c-Fos. Our results identify a new, previously unreported role for c-Jun/AP-1 in regulation of cell cycle progression and mammalian cell growth. PMID- 1900356 TI - Co-induction of jun B and c-fos in a subset of neurons in the spinal cord. AB - Noxious stimulation in vivo provokes the transcriptional activation of several genes which are thought to play an important role in the phenomena of stress and pain. In the rat, the expression of the c-fos proto-oncogene is rapidly induced upon noxious stimulation in defined neurons in the dorsal horn of the spinal cord. Interestingly, expression of the prodynorphin gene, which is thought to be involved in the endogenous mechanisms for pain/stress control, also localizes in the same anatomical area. Fos proteins are known to associate in transcriptional complexes with the products of the jun family constituting nuclear factor AP-1. These considerations prompted us to analyse the expression of the jun gene family members c-jun, jun B and jun D in rats subjected to noxious stimulation. We present data indicating that in unstimulated animals the transcripts of the three genes are differentially expressed and abundant within the various laminas of the lumbar spinal cord. Surprisingly, upon stimulation only the jun B transcript is augmented, being co-localized with Fos in a subset of neurons of the medial dorsal horn. PMID- 1900358 TI - The proto-oncogene c-ros codes for a transmembrane tyrosine protein kinase sharing sequence and structural homology with sevenless protein of Drosophila melanogaster. AB - Our earlier study predicted that proto-oncogene c-ros codes for a receptor-like tyrosine protein kinase (TPK). To further understand its protein structure and physiological function, we have analysed its expression in various tissues of chicken and have isolated and sequenced cDNA clones containing the entire coding region of the gene. Confirming our earlier study, we found that kidney is the organ that expresses the highest level of c-ros mRNA, in addition, we found a lower level of expression in gonad, thymus, bursa and brain. A distinctive 8.3 kb c-ros mRNA is present in kidney. No detectable amount of c-ros mRNA was found in the rest of tissues examined. Nucleotide sequence of the c-ros cDNA predicts that it codes for a transmembrane (TM) TPK molecule of 2311 amino acids (aa). The extracellular domain consists of 1873 amino acids which share 20 to 43% homology with that of the Drosophila sevenless protein and TPK domains of the two genes have 58 to 74% homology. The extracellular domain containing 37 potential N linked glycosylation sites is preceded by a 5' hydrophobic sequence resembling a typical signal peptide. An internal hydrophobic domain of 26 amino acids, the presumed transmembrane domain, is followed by a spacer sequence of 58 amino acids, a TPK domain of 270 amino acids and a carboxyl tail of 84 amino acids. Overall, our result indicates that c-ros codes for a glycosylated transmembrane TPK molecule which shares a remarkable sequence and structural homology with that of Drosophila sevenless protein. PMID- 1900359 TI - A pediatrician's view. The first seizure--a terrifying event. PMID- 1900360 TI - Using a learning contract to successfully discharge an infant on home total parenteral nutrition. AB - Discharging an infant on home total parenteral nutrition is a complex process involving a variety of health care team providers and family members. Development of a learning contract can bring cohesion and provide a framework for discharge. PMID- 1900362 TI - Generation of free radicals in lipid emulsion used in parenteral nutrition. AB - Lipid emulsions used in parenteral nutrition are prone to peroxidation that may be an important feature of oxygen-associated tissue damage. Incubation of lipid emulsion [Intralipid (IL)] with H2O2 and FeCl2 increased lipid peroxidation, measurable as increased production of pentane, from 0.39 +/- 0.33 to 0.99 +/- 0.18 microM (p less than 0.0001). Malondialdehyde was increased from 0.010 +/- 0.005 mM to 0.380 +/- 0.025 mM (p less than 0.001). Superoxide dismutase and catalase (each 100 U/mL) or vitamin C (10 mM) inhibited pentane and malondialdehyde production (p less than 0.0001). Incubation of human erythrocytes in the presence of FeCl2 caused 11.0 +/- 3.2% hemolysis (control 0.95 +/- 0.14%). Addition of 0.44% IL increased hemolysis to 66.5 +/- 3.4%, whereas further addition of vitamin E or C significantly inhibited hemolysis to 16.4 +/- 8.1 and 38.9 +/- 7.1%, respectively (p less than 0.0001). IL was administered i.v. to eight preterm infants. It increased 3- to 28-fold (p less than 0.001) the amount of pentane in expired breath. Partly, this increase was due to pentane dissolved in IL as a result of lipid peroxidation during storage. After discontinuing IL infusion, the elimination of pentane was nonexponential, consisting of a rapid and a slow component. According to our results, IL undergoes peroxidation causing free-radical-dependent damage to human cells. We propose that the adverse effects of parenteral IL are partially caused by free oxygen radicals generated by lipid peroxidation. PMID- 1900361 TI - Intestinal apolipoprotein synthesis in the newborn piglet. AB - To determine the effects of dietary and biliary lipid absorption on intestinal apo B-48 and apo A-I synthesis in the newborn piglet, 2-d-old female piglets were prepared with a duodenal infusion catheter. After recovery, animals were given either low triglyceride (Vivonex; VIV group) or high triglyceride (Intralipid; FAT group) diets by continuous intraduodenal infusion for 24 h. A bile-diverted group was also studied. Segments of proximal jejunum and distal ileum were then pulse-radiolabeled in vivo with 3H-leucine. Mucosal apo B-48 and apo A-I were immunoprecipitated, and apoprotein synthesis was expressed as percentage of total protein synthesis. Mucosal apoprotein content (ng apoprotein/microgram total protein) was measured by competitive ELISA assays. In jejunum and ileum, apo B-48 synthesis was not different in the three groups. However, apo B content increased 2.4-fold in jejunum and 1.7-fold in ileum in the FAT group compared with the VIV group. Immunoblotting revealed the majority of jejunal apo B to be apo B-48, not apo B-100 from contaminating plasma lipoproteins, in all three experimental groups. Bile-diverted animals had decreased jejunal apo B content compared with the VIV group. Jejunal apo A-I synthesis and content were approximately 2-fold higher in FAT animals compared with the VIV group. Although ileal apo A-I synthesis was also 2-fold higher in the FAT group, apo A-I content was not different from the VIV group. Neither jejunal nor ileal apo A-I synthesis was significantly affected by bile diversion, even though jejunal apo A-I content was decreased by over two thirds compared with the VIV animals. In the newborn piglet, intestinal synthesis of apo B-48 and apo A-I is differentially regulated by luminal lipid absorption. Although fat feeding and bile diversion regulate mucosal apo B-48 content, synthesis is unchanged, indicating a posttranslational regulatory mechanism.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1900363 TI - Common ankle injuries in the athlete. AB - The ankle is often a neglected joint by the athlete because of an inadequate understanding of the injury. Sprains and fractures are common injuries in the athlete because of the force of impact on the ankle during activity. Appropriate management of ankle injuries promotes healing and prompt return to sports activities. PMID- 1900364 TI - Association of the Ras-antagonistic Rap1/Krev-1 proteins with the Golgi complex. AB - Ras oncogenes encode 21-kDa GTP-binding proteins that are capable of transforming immortalized cells in culture. Ras proteins are bound to the inner face of the plasma membrane by their C-terminal extremity and are thought to transmit their mitogenic signals via an "effector" domain spanning amino acids 32-42. Two ras related human genes rap1A and rap1B encode 95% homologous 21-kDa proteins that share with Ras p21 the same effector domain and a similar C-terminal Cys-Ali-Ali Xaa sequence (where Ali is an aliphatic amino acid; also known as a CAAX sequence). The product of the rap1A gene is identical to that of the Krev-1 cDNA, whose overexpression is capable of reverting the phenotype of Ki-ras-transformed NIH 3T3 cells. Antibodies that do not cross-react with Ras and other Ras-related proteins were obtained by immunizing rabbits with a peptide encompassing residues 121-137 of Rap1 proteins. These antibodies were used to investigate the subcellular localization of Rap1 proteins by indirect immunofluorescence and fractionation techniques. Rap1 proteins were found to be tightly bound to cellular membranes. They did not colocalize with Ras proteins on the plasma membrane and were discovered to be associated with the Golgi complex. PMID- 1900365 TI - Concerted evolution of duplicated protein-coding genes in Drosophila. AB - Very rapid rates of gene conversion were observed between duplicated alpha amylase-coding sequences in Drosophila melanogaster. This gene conversion process was also seen in the related species Drosophila erecta. Specifically, there is virtual sequence identity between the coding regions of the two genes within each species, while the sequence divergence between species is close to that expected based on their phylogenetic relationship. The flanking, noncoding regions are much more highly diverged and do not appear to be subject to gene conversion. Comparison of amylase sequences between the two species provides a clear demonstration that recurrent gene conversion does indeed lead to the concerted evolution of the gene pair. PMID- 1900366 TI - Purification of the regulatory protein AlgR1 and its binding in the far upstream region of the algD promoter in Pseudomonas aeruginosa. AB - A regulatory protein AlgR1, previously suggested to be a member of a two component sensory transduction system because of its homology to OmpR and NtrC and its ability to allow activation of the algD promoter under conditions of high osmolarity, has been hyperproduced in Escherichia coli after deletion of the upstream region including part of the Shine-Dalgarno sequence of the algR1 gene and its subsequent cloning under the tac promoter. The AlgR1 protein is purified as a monomer, and the sequence of the nine N-terminal amino acids of the monomer matches with that predicted from the DNA sequence of the algR1 gene. The purified AlgR1 protein binds to two separate DNA fragments of the algD upstream region. DNase protection experiments identify these two DNA segments as 14-mer sequences centered at -382 and -458 regions, which contain a common CCGT-TCGTC sequence in them. While the presence of at least one AlgR1 binding site is important for the activation of the algD promoter, the presence of both of the binding sites in the upstream region leads to a higher level of activation. PMID- 1900367 TI - Expression of the amyloid precursor protein gene in mouse oocytes and embryos. AB - The amyloid precursor protein (APP) is thought to be processed aberrantly to yield the major constituent of the amyloid plaques observed in the brains of patients with Alzheimer disease and Down syndrome. However, the gene encoding APP is expressed widely in normal human tissues and in adult and fetal mouse tissues and is alternatively spliced in a tissue-specific pattern in the adult. There is evidence that APP may function as a growth factor and as a mediator of cell adhesion and in these roles could be important in morphogenesis. As a step toward determining the role of APP in development and in determining how the adult pattern of tissue-specific splicing is established, we have used reverse transcription and the polymerase chain reaction to demonstrate APP expression in mouse oocytes, preimplantation embryos, and postimplantation embryonic stages to the late embryonic period. All three splicing forms described in mouse were present at each stage, although there were changes in the ratios of the splicing forms at different stages. Screens for APP clones in embryonic cDNA libraries from the egg cylinder stage and the early somite stage were used to confirm the results of the polymerase chain reaction, and APP clone abundance was found to increase 10-fold between the two stages. PMID- 1900368 TI - Host-plant specialization in the Drosophila melanogaster species complex: a physiological, behavioral, and genetical analysis. AB - Drosophila sechellia, endemic to the Seychelles, breeds in a single resource, Morinda citrifolia, whereas its close sympatric relative, Drosophila simulans, is a cosmopolitan generalist breeding in a great variety of resources. The effects of morinda on various fitness traits of these two species, their F1 hybrids, and reciprocal backcrosses were analyzed. Morinda fruit is highly toxic to Drosophila species, except D. sechellia. The toxicity is expressed in adults, embryos, and larvae. In embryos, early mortality is a maternally inherited trait, depending only on mother's genotype. The tolerance of D. sechellia to morinda is fully dominant in F1 hybrids. Egg production is stimulated by morinda in D. sechellia but inhibited in D. simulans; in hybrids, the inhibition observed in D. simulans is dominant. Morinda is an oviposition attractant for D. sechellia but a repellent for D. simulans; F1 hybrids and backcross individuals exhibit intermediate, approximately additive, behavior. In the field, adult flies of the two species exhibit opposite behavior in that D. sechellia is attracted to morinda and D. simulans is attracted to banana; hybrids have an intermediate behavior. These differences between the species explain why they do not hybridize in nature although living in sympatry. The various traits have different genetic bases: three or four different genes, or groups of genes, differentiate the ecological niches of the two species. PMID- 1900370 TI - A tube to suit all NG needs? Evaluation of fine bore nasogastric tubes. AB - Nutrition nurses are faced with a wide choice of nasogastric tubes, all of which claim to meet specialist needs. The NNS and nurses at the Royal London Hospital set up a trial to assess the tubes' individual benefits, and apply them to patient needs. PMID- 1900369 TI - Mutasynthesis of siderophore analogues by Pseudomonas aeruginosa. AB - The Gram-negative bacterium Pseudomonas aeruginosa produces the phenolic siderophore pyochelin. Salicylic acid is an intermediate in the pyochelin biosynthetic pathway, and mutants blocked in salicylic acid biosynthesis (Sal-) are able to incorporate exogenously supplied salicylic acid into pyochelin. A P. aeruginosa Sal- mutant was incubated with 13 salicylic acid analogues and was found to incorporate three (5-fluorosalicylic acid, 4-methylsalicylic acid, and 3 hydroxypicolinic acid) into pyochelin analogues, trivially designated as 5 fluoropyochelin, 4-methylpyochelin, and 6-azapyochelin. The structures of the mutasynthetic products were confirmed by 1H and 13C NMR and high-resolution fast atom bombardment mass spectrometry as being identical to pyochelin except for the expected changes in the aromatic ring. The biological activity of the three pyochelin analogues was determined in iron transport assays. In comparison to pyochelin, 4-methylpyochelin was more active in the assays whereas the activities of 5-fluoropyochelin and 6-azapyochelin were markedly decreased. In coincubation assays, 5-fluoropyochelin substantially inhibited iron transport by pyochelin; 4 methylpyochelin and 6-azapyochelin did not demonstrate this inhibitory effect. PMID- 1900371 TI - A uv-sensitive Chinese hamster lung fibroblast cell line (V79/UC) with a possible defect in DNA polymerase activity is deficient in DNA repair. AB - Studies of repair enzyme activities in a uv-sensitive cell line (V79/UC) derived from Chinese hamster V79 cells have revealed levels of total DNA polymerase that are about 50% of the levels in the parental cell line. There are a number of DNA polymerase inhibitors available which allow us to distinguish between the major forms of DNA polymerase (alpha, beta, gamma, and delta) identified in mammalian cells. Enzyme assays with these inhibitors indicate that the aphidicolin sensitive DNA polymerase is defective in the V79/UC cell line. This could be either polymerase alpha or delta, or both. The V79/UC cells do not express resistance to aphidicolin in standard toxicity studies. However, when aphidicolin is added postirradiation in survival assays designed to measure the extent of inhibitable repair, V79/UC cells do not respond with the further decrease in survival seen in the parental line. Further evidence of a polymerase-dependent repair defect is evident from alkaline elution data. In this case the V79/UC cells show the appearance of single-strand breaks following uv irradiation in the absence of any added inhibitor. Cells of the V79/M12G parental line, on the other hand, show the appearance of single-strand breaks only when aphidicolin is present. PMID- 1900372 TI - Radiation-induced progression delay in HeLa cells blocked in S phase by aphidicolin. AB - The duration of the cell cycle in synchronous cultures of HeLa S3 cells that were either irradiated with 3.5 Gy of 220-kV X rays in mid-S phase or treated in early G1 or mid-S phase for several hours with 1 or 3 microM aphidicolin, or were subjected to both treatments, was measured by time-lapse cinemicrography. When compared with the generation time of untreated cells, the delay in cell progression with the combined treatment was found to be less than the sum of the delays with the individual treatments, but longer than the imposed delay caused by treatment with aphidicolin alone. Because recovery from potentially lethal radiation damage proceeds in the presence of aphidicolin, this finding suggests that a portion of the radiation-induced delay in cell progression may be associated with processes other than those that directly affect cell viability. It was also observed that the incidence of both spontaneous and radiation-induced sister-cell fusion is decreased in cultures incubated in the presence of aphidicolin. PMID- 1900373 TI - Mutation identified as a possible cause of Alzheimer's disease. PMID- 1900374 TI - Magnetic resonance appearance of peripheral nerve sheath tumors. AB - Magnetic resonance imaging (MRI) was used to evaluate 22 histologically proven peripheral nerve sheath tumors, approximately two-thirds of which arose in the lower extremity. The histologic distribution was as follows: 12 schwannomas, 7 neurofibromas, and 3 malignant peripheral nerve sheath tumors (2 of which occurred in patients with neurofibromatosis). Most lesions demonstrated an intermediate to moderately bright signal on T1-weighted images and were minimally inhomogeneous. All lesions were moderately bright on proton-density-weighted images and bright on T2-weighted images, again with variable inhomogeneity. The extent of the tumor was best assessed on proton-density- and T2-weighted images. Smooth margins were noted in 19 lesions. Of the 3 remaining lesions, 2 were malignant (but had been subjected to biopsy prior to MRI), and the other lesion was a plexiform neurofibroma. MRI accurately determined the relationship between the lesion and the adjacent neurovascular structures and muscles, thereby assisting surgical management. On MRI, 5 lesions demonstrated coexistent subtle muscle atrophy along the longitudinal axis of surrounding or distally innervated musculature. This latter finding, together with the presence of a tumor in the vicinity of a large nerve trunk, suggests a peripheral nerve sheath neoplasm. PMID- 1900375 TI - Gastric mucosal injury induced by nonsteroidal anti-inflammatory drugs. PMID- 1900376 TI - [Reintroduction of state activities. Problems of the health sector seen from a renewal's perspective]. AB - Medical knowledge is increasing and calls for a flexible public health service. The counties' responsibility for the public health service makes this difficult. A National Hospital Council would ensure that the decentralized public health services makes full use of the country's total resources, without the transfer of money between different administrative levels at additional cost to the patient during serious illness. The article discusses management and administration of hospitals. The DRG-System is compared with the system of payment for patients' stay in hospital. The previous nationally appointed district doctor arrangement is discussed in relation to the present local community doctor arrangement. PMID- 1900377 TI - Two new applications for 3M Steri-Drape "O'Connor rectal shield". PMID- 1900378 TI - Total TRH response in TRH test. PMID- 1900379 TI - Pituitary function in thalassemic patients and the effect of chelation therapy. AB - This study examined anterior pituitary function and the effect of chelation therapy in 31 patients with beta-thalassemia/HbE disease. Patients were divided into those receiving chelation therapy by deferoxamine and those receiving no such therapy (control group). Pituitary function studies were repeated in both groups 18 months later. The results showed decreased pituitary responses following stimulation in 22 patients. Among these, gonadotropin and PRL responses were most affected. After 18 months, serum ferritin levels had significantly decreased in the deferoxamine group. PRL and GH responses were improved in 3 patients receiving chelation therapy without changes in other hormone responses. In contrast, no changes in pituitary responses were shown in the control group at the end of follow-up. There were 6 drop-outs (4 in the control and 2 in the deferoxamine group) and 3 deaths (2 in the control and 1 in the deferoxamine group) during 18 months. In conclusion, gonadotropin and PRL deficiencies occur most frequently in thalassemic patients. Chelation therapy for 18 months markedly reduced serum ferritin level and might preserve or improve PRL and GH secretions, but seems to have no beneficial effects on other pituitary hormone reserves. PMID- 1900380 TI - Effects of a novel gonadotropin-releasing hormone antagonist (ORG 30850) on gonadotropin and prolactin secretion by rat pituitary cells in culture. AB - The effect of a new GnRH antagonist (ORG 30850 ANT) on FSH, LH, and PRL secretion was studied using male rat pituitary cells in monolayer cell culture. In the absence of GnRH, ORG 30850 ANT did not alter spontaneous FSH and LH secretion into culture medium or the cell content of these hormones. In the presence of GnRH (10(-8) mol/l), ORG 30850 ANT significantly and dose-dependently inhibited FSH and LH secretion into culture medium while increasing their cell content. Conversely, in the presence of a single dose of ORG 30850 ANT, FSH and LH secretion rose significantly when subjected to increasing amounts of GnRH, whereas the hormonal cell content diminished. Furthermore, inhibition of GnRH induced FSH and LH release by ORG 30850 ANT was not changed by pre-incubation with the GnRH antagonist regardless of the pre-incubation time. The inhibitory effect of the GnRH antagonist was observed early, with its peak occurring within 6 h of culture. These short-term studies indicate that ORG 30850 ANT specifically inhibits GnRH-induced gonadotropin release into culture medium, exerts no effect on the rate of gonadotropin production in the presence or absence of GnRH, competitively and reversibly inhibits the binding of natural GnRH to its receptors, and does not lead to any modifications in PRL secretion. PMID- 1900381 TI - The use of intraaortic balloon pumping as an adjunct to reperfusion therapy in acute myocardial infarction. The Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) Study Group. AB - To assess the risk and possible benefits of use of the percutaneous IABP in patients given thrombolytic therapy as treatment for acute myocardial infarction, we prospectively evaluated 810 consecutive patients entered into the TAMI trials. During hospitalization the 85 patients treated with the IABP had more cardiac risk factors, were slightly older (58 vs 56 years), and more often had anterior infarction (62% vs 38%). At acute cardiac catheterization, patients treated with the IABP also had more multivessel coronary disease (67% vs 43%), more frequent TIMI grade 0 or 1 flow (44% vs 28%), lower global ejection fraction (40% vs 52%), and worse regional infarct (-3.2 vs -2.5 SD/chord) and noninfarct (-0.67 vs +0.36 SD/chord) zone function. Although mortality rates (32% vs 4%) and in-hospital complications were greater in patients treated with the IABP, a greater improvement in global (delta ejection fraction: +1.9% vs +0.7%) and noninfarct zone (delta SD/chord: +0.11 vs -0.09) left ventricular function was observed in patients treated with the IABP at 1-week follow-up angiography. In addition, no reinfarction or reocclusion of the infarct-related artery occurred while patients were being treated with the IABP. These results suggest that the IABP may have a specific role after thrombolytic therapy in treating patients at high risk for reocclusion or at high risk for hemodynamic deterioration because of large infarction or critical stenoses in coronary vessels supplying the noninfarct zone. PMID- 1900382 TI - Protein-energy undernutrition and the risk of mortality within 1 y of hospital discharge in a select population of geriatric rehabilitation patients. AB - To determine whether undernourished elderly patients are at increased risk for mortality, independent of nonnutritional factors affecting outcomes, 109 patients were evaluated at admission to a geriatric rehabilitation unit (GRU) and then followed prospectively for 1 y after hospital discharge. During the interval of observation, 33 (30%) patients died, 11 before hospital discharge and 22 within the year subsequent to discharge. Of the 81 nutritional and nonnutritional variables analyzed, the best predictor of mortality, as determined by stepwise discriminant-function analysis, within 1 y of hospital discharge was the percent of usual body weight lost in the year previous to admission, followed by the subscapular skinfold thickness and the discharge Katz Index of Activities of Daily Living (ADL) score. Percent of weight lost was also the strongest predictor of 1-y post-GRU-admission mortality. These results provide compelling evidence for the importance of nutritional status in predicting both in-hospital and postdischarge mortality in a population of frail, male GRU patients. PMID- 1900383 TI - Lowering of HDL2-cholesterol and lipoprotein A-I particle levels by increasing the ratio of polyunsaturated to saturated fatty acids. AB - The protective role of high-density lipoproteins (HDLs) has been attributed to the subfractions HDL2 (according to the density) and lipoprotein A-I (LpA-I) (according to the composition in apolipoproteins). We investigated the effect of a high ratio of polyunsaturated to saturated fatty acids (P:S) on these subfractions in a homogeneous group of young adult males. Two prescribed diets were consumed successively at the subjects' homes for 3 wk each in a random order; one diet contained 70 g butter (P:S 0.2, diet B), the other contained 70 g sunflower margarine (P:S 1.1, diet M). Total calorie, fat, and cholesterol intakes were similar for the two diets. Cholesterol and apolipoprotein B in serum and in low-density lipoproteins (LDLs) were lower with diet M than with diet B. However, significant decreases in protective subfractions of HDL, HDL2, and LpA-I were observed. This undesirable effect of the diet with a high P:S could cancel the benefits of lowering the LDL-cholesterol concentrations. PMID- 1900384 TI - Lack of effect of linoleic acid on the high-density-lipoprotein-cholesterol fraction of plasma lipoproteins. AB - Low-fat, natural diets were fed to 11 middle-aged, healthy male subjects for two 40-d periods to determine effects on plasma lipoproteins. The diets were designed to maintain saturated and monounsaturated fatty acids at 10 en% and linoleic acid (LA) at 3.8 and 10.8 en%. When compared with baseline concentrations, total cholesterol decreased 10% at the end of the lower LA diet and 15% at the end of the higher LA diet. Low-density-lipoprotein cholesterol (LDL-C) decreased 18% and 22%, respectively, during the same periods. Plasma high-density-lipoprotein cholesterol (HDL-C) at the end of each dietary period was not significantly different but the midpoint values were lower by 12.5% on the lower LA diet and 7.3% on the higher LA diet. Apolipoprotein B decreased 27% at the end of the lower LA diet and 37% at the end of the higher LA diet whereas apolipoprotein A-I increased 18% and 24%, respectively. HDL-C was not reduced by dietary LA over a 6 wk period. PMID- 1900385 TI - Tumor cytokinetic response to total parenteral nutrition in patients with head and neck cancers. AB - Refeeding of patients with malignant tumors may induce tumor-cell DNA synthesis. The present study was aimed at evaluating whether induction of altered cell-cycle kinetics could be induced by intravenous total parenteral nutrition (TPN) in tumor biopsies from head and neck cancers. Nine malnourished patients with squamous cell carcinoma in the head-and-neck area were investigated before and after 5-7 d of continuous TPN. Tumor biopsies were taken in both fasted and fed states for determination of 1) ornithine decarboxylase (ODC) activity, which is rate limiting for polyamine synthesis; 2) flow-cytometric-DNA-distribution measurements; and 3) the fraction of proliferating cells expressed as immunohistochemical reactivity with the monoclonal antibody Ki-67. The histopathological differentiation, the fraction of aneuploidic cells, ODC activity, and Ki-67 reactivity were not significantly related to each other, although the number of aneuploidic cells in replicative phases correlated with the number of cells expressing the Ki-67 antigen (r = 0.86, P less than 0.01). Tumor cytokinetics showed no evidence of being changed by TPN administration. PMID- 1900386 TI - Audit of ranitidine administration in parenteral nutrient solutions. AB - An audit of the use of ranitidine administered in parenteral nutrient (PN) solutions is reported. Pharmacists at a 747-bed teaching institution developed criteria addressing justification of the use of ranitidine in PN solutions, process indicators for monitoring, and outcome measures. All patients who received ranitidine in their PN solutions between October 29 and November 22, 1989, were included in the study. Data were collected on a standardized form. A total of 23 evaluable patients received ranitidine in PN solutions during the study period. No inappropriate uses of ranitidine were identified. Patients with renal impairment tended to be underdosed. There were no duplicate administrations of ranitidine by the i.v. minibag and PN solution routes. However, on four occasions the PN solution was interrupted for more than six hours; additional ranitidine by i.v. minibag was ordered for only one of these patients. Testing of nasogastric aspirates for pH was not performed in 17 of the 22 patients who needed this test. Gastrointestinal bleeding was observed in two patients, both of whom were not monitored for gastric pH and were underdosed. A program is being developed to promote the safe and effective use of ranitidine administered in PN solutions. An audit of the administration of ranitidine in PN solutions showed that the drug is usually used appropriately at the institution and that most of the patients had positive clinical outcomes. PMID- 1900387 TI - Paraproteinemic corneal deposits in plasma cell myeloma. AB - We treated two patients who had IgG-kappa-light chain monoclonal gammopathy with partially crystalline and partially amorphic corneal deposits. Impairment of vision made keratoplasty necessary for each patient. Histologic examination of the corneal specimens showed deposits that stained positively for Masson's trichrome in all corneal cells. Immunohistochemical tests identified these deposits as IgG-kappa-light chain immunoglobulin fragments. Electron microscopy showed intracellular, rhomboid-shaped deposits enveloped by a membrane. The same deposits appeared in the conjunctival epithelium, within subconjunctival fibrocytes, and in the plasma cells of the bone marrow. Immunoelectrophoresis showed IgG-kappa-light chain fragments in the blood serum, the lacrimal film, and the aqueous humor. This suggests that the intracellular immunoglobulin fragments may have entered the corneal and conjunctival epithelium by way of the lacrimal film, the keratocytes by way of the corneo-scleral limbus vasculature, and the endothelial cells from the aqueous humor. PMID- 1900388 TI - bcl-1 rearrangement. Frequency and clinical significance among B-cell chronic lymphocytic leukemias and non-Hodgkin's lymphomas. AB - The authors investigated the structural organization of the bcl-1 locus, a putative oncogene associated with reciprocal chromosomal translocation t(11;14), by Southern blot hybridization analysis and its frequency, distribution, and prognostic significance in a panel of 156 clinically and pathologically well defined B-cell chronic lymphocytic leukemias (CLLs) and non-Hodgkin's lymphomas (NHLs). The authors detected bcl-1 rearrangements in only 2 of 42 CLLs and 4 of 114 NHLs, specifically 3 of 29 diffuse small lymphocytic and 1 of 10 diffuse small cleaved cell and none of 5 diffuse intermediate lymphocytic, 13 follicular predominantly small cleaved, 17 follicular mixed small cleaved and large cell, 4 diffuse mixed small and large cell, 26 diffuse large cell, and 10 diffuse small noncleaved cell lymphomas. None of seven cases of Rai stage III or IV CLL or seven diffuse large cell lymphomas occurring as Richter's syndrome exhibited bcl 1 rearrangements. In conclusion, the bcl-1 locus rearranges in only about 4% of B cell CLLs and NHLs, is predominantly rearranged in low-grade B-cell neoplasms, and does not appear to be preferentially associated with those occasional CLLs and low-grade NHLs displaying clinical aggressiveness, advanced clinical stage, or large cell transformation (Richter's syndrome). Therefore the demonstration of bcl-1 rearrangement does not appear to have clinically useful prognostic significance. PMID- 1900389 TI - A pertussis toxin-sensitive GTP-binding protein couples endothelin to phospholipase C in rat mesangial cells. AB - The mechanisms of stimulation of phospholipase C (PLC) by endothelin, specifically the role of guanine nucleotide-binding proteins (GTP-binding proteins) in coupling the endothelin receptor to PLC, were investigated in rat mesangial cells. Endothelin-1 (ET) synergistically released inositol polyphosphates in the presence of the stimulatory GTP analogue guanosine 5'-O-(3 thiotriphosphate) (GTP gamma S) in permeabilized cells. In addition, in intact cells, pertussis toxin partially inhibited the stimulation of total inositol phosphates (IPn) by ET. Pertussis toxin also reduced the peak ET-stimulated intracellular free calcium level ([Ca2+]i) in these cells, both in the presence and absence of extracellular calcium. Pertussis toxin induced ADP ribosylation of a 41- to 43-kDa protein in mesangial cell membranes, and this effect was inhibited by prior exposure to ET and augmented by the inhibitory GDP analogue, guanosine 5'-O-(2-thiodiphosphate) (GDP beta S). Thus a pertussis toxin-sensitive GTP-binding protein is involved in the activation of PLC by ET in glomerular mesangial cells. PMID- 1900390 TI - Role of intracellular calcium in volume regulation by rabbit medullary thick ascending limb cells. AB - Previous studies demonstrated that Ca2(+)-activated K+ channels in luminal membrane of rabbit medullary thick ascending limb cells (MTAL) are activated on exposure of the cells to hyposmotic solutions [J. Taniguchi and W. B. Guggino. Am. J. Physiol. 257 (Renal Fluid Electrolyte Physiol. 26): F347-F352, 1989]. In this study, we investigated the mechanism of activation of Ca2(+)-activated K+ channels in MTAL cells exposed to hyposmotic solutions. MTAL cells swell in hyposmotic medium and regulate volume back toward the starting volume. This regulatory volume decrease (RVD) is inhibited at high medium K+ concentrations or by presence of quinine or Ba2+ in extracellular medium, suggesting involvement of K+ channels. Measurements of intracellular Ca2+ concentrations with fura-2 show that intracellular Ca2+ rises in hyposmotic solutions and that this rise does not occur in absence of extracellular Ca2+. Nifedipine and verapamil also inhibit rise in intracellular Ca2+. Decreasing intracellular Ca2+ by removal of external Ca2+ in presence of EDTA or by chelation of intracellular Ca2+ with 1,2-bis(2 aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) inhibits RVD. We conclude that hypotonic solutions activate K+ efflux probably via K+ channels and Ca2+ influx via a nifedipine- and verapamil-sensitive pathway. Lowering intracellular Ca2+ removes the ability of MTAL cells to regulate volume in hyposmotic solutions. PMID- 1900391 TI - Interactions between nitroglycerin and endothelium in vascular smooth muscle relaxation. AB - To evaluate the role of endothelium in nitroglycerin (NTG)-mediated vascular relaxation, epinephrine-contracted rat thoracic aortic segments with and without intact endothelium were exposed to NTG (10(-10) to 10(-5) M). Aortic segments with intact (endo+, n = 15) and denuded endothelium (endo-, n = 9) exhibited typical NTG-induced relaxation. However, the mean effective concentration of NTG was lower for endo- than for endo+ segments (P less than 0.001). To determine if this phenomenon related to nitric oxide (NO) generation by endothelium, six endo+ segments were treated with NG-monomethyl-L-arginine (L-NMMA), an inhibitor of NO production. These endo+ segments exhibited greater (P less than 0.001) relaxation in response to NTG than the untreated endo+ segments. Oxyhemoglobin, an inhibitor of guanylate cyclase activation, greatly diminished NTG-mediated relaxation of all aortic segments. To determine if the enhanced NTG-mediated relaxation of endo segments was unique to the guanosine 3',5'-cyclic monophosphate-dependent vasodilator NTG, other endo+ and endo- segments were exposed to adenosine 3',5' cyclic monophosphate-dependent vasodilator papaverine (10(-8) to 10(-4) M), and no difference in EC50 was noted between endo+ and endo- segments. Thus endothelium attenuates NTG-mediated vasorelaxation, and this attenuation is abolished by inhibition of endothelial NO production with L-NMMA. These observations indicate that endothelium is a dynamic modulator of vascular smooth muscle relaxant effects of NTG. This modulation appears to result from a competitive interaction between endothelial NO and NTG. PMID- 1900392 TI - Stimulation of arterial 42K efflux by ATP depletion and cromakalim is antagonized by glyburide. AB - It has been suggested that cromakalim (BRL 34915)-induced vasorelaxation was associated with stimulation of ATP-sensitive K channels. The hyperpolarization resulting from activation of this mechanism might then inhibit voltage-dependent Ca2+ entry and subsequent contraction. The present study evaluated the similarities of 42K efflux stimulated by ATP depletion (verified by high performance liquid chromatography) and by exposure to cromakalim (10 microM) in rabbit superior mesenteric arteries. Both depletion of intracellular ATP and exposure to cromakalim significantly stimulated 42K efflux (P less than 0.05). Glyburide (a selective inhibitor of ATP-sensitive K channels in pancreatic beta cells) inhibited 42K efflux stimulated by ATP depletion and by cromakalim exposure. Glyburide (10 microM) had no significant effect on either basal 42K or the 42K efflux stimulated by norepinephrine and by K depolarization, which cause voltage and Ca2(+)-dependent activation of K channels. Glyburide therefore had a relatively selective effect on vascular smooth muscle. The glyburide-sensitive 42K efflux during ATP depletion and exposure to cromakalim was greatest in Ca2(+) free solution (Mg raised to 10 mM). We conclude that in vascular smooth muscle both depletion of ATP and exposure to cromakalim stimulate 42K efflux via a glyburide-sensitive mechanism with properties similar to those of ATP-sensitive K channels observed in cardiac and pancreatic beta-cells. PMID- 1900393 TI - Block of calcium-activated potassium channels in mammalian arterial myocytes by tetraethylammonium ions. AB - The effects of tetraethylammonium ions (TEA+) and tetrapentylammonium ions (TPeA+) on Ca2(+) -activated K+ (KCa) channels were studied in membrane patches from mesenteric arterial myocytes. External TEA+ produced a flickery block. The concentration dependence for reduction in mean unitary current was consistent with 1:1 binding, with dissociation constants (Kd) in rat and rabbit of 196 and 159 microM at 0 mV, and the block was weakly voltage dependent. Rate constants for blocking and unblocking were 380 mM-1.ms-1 and 73 ms-1, respectively. In patches containing several channels TEA+ reduced average current to the same extent as mean unitary current, implying that TEA+ block is independent of the channel state. Block was unaffected by raising external K+ to 120 mM. External TPeA+ blocked with slower kinetics and lower affinity than TEA+ (Kd, 1.49 mM). The sulfonylurea glibenclamide (10-100 microM), the hyperpolarizing vasodilator cromakalim (5 microM), and internal ATP (1 mM) were without effect on channel activity. We conclude that TEA+ is a relatively effective blocker of single KCa channels of arterial smooth muscle and should block macroscopic currents equally well, whereas external TPeA+ is about eight times less effective. PMID- 1900394 TI - Distribution of dietary limiting amino acid injected into the prepyriform cortex. AB - Diffusion or metabolism of the dietary limiting amino acid (DLAA) in the prepyriform cortex (PPC) may account for the time lag between injection of the DLAA into the PPC and the increase in intake of an amino acid-imbalanced diet. Results from the injection of [3H]Leu +/- [14C]Thr (DLAA) into the PPC indicated rapid (less than 15 min) and limited diffusion (85-90% of recovered label was less than or equal to 1 mm from the injection site). 3H and 14C decreased in the trichloroacetic acid (TCA)-soluble fraction and increased in the TCA-insoluble fraction during the first 1.5 h and remained constant in the TCA-insoluble fraction 1.5-6 h after injection. An increase (approximately 50%) in 3H in the TCA-insoluble fraction was found less than or equal to 30 min after injection of the DLAA. There was no affect of the DLAA on 3H in the TCA-soluble fraction. These results indicated that a change in metabolism within the PPC may be responsible for the delay in onset of the feeding response after injection of the DLAA into the PPC. PMID- 1900395 TI - The role of desflurane in the practice of anesthesia. PMID- 1900396 TI - Depression of ventilation by desflurane in humans. AB - We studied the ventilatory effects of desflurane (formerly I-653) with and without N2O in healthy male volunteers. After insertion of venous and arterial (radial and pulmonary) catheters, baseline measurements of tidal volume (VT), respiratory rate (RR), ventilatory response to CO2, and arterial and mixed venous blood gases were made. Subjects were randomly assigned to receive either desflurane with O2 (n = 6) or with O2 and 60% N2O (n = 6). Anesthesia was induced by inhalation of desflurane followed by tracheal intubation without muscle relaxants. In each volunteer, at end-tidal concentrations totaling 0.83, 1.24, and 1.66 MAC, we repeated measurements of VT, RR, response to CO2, and arterial and mixed venous blood gases. As depth of anesthesia increased, VT significantly (P less than 0.05) decreased from 363 +/- 22 ml awake to 76 +/- 22 ml at 1.66 MAC without N2O and from 473 +/- 70 ml awake to 128 +/- 6 ml at 1.66 MAC with N2O (mean +/- SE). Similarly, RR increased from 15 +/- 0.5 breaths per min awake to 32 +/- 2 breaths per min at 1.66 MAC without N2O and from 14 +/- 0.5 breaths per min awake to 40 +/- 3 breaths per min at 1.66 MAC with N2O. Desflurane without N2O depressed the ventilatory response to CO2 to 45 +/- 9, 31 +/- 5, and 11 +/- 4% of the awake values at 0.83, 1.24, and 1.66 MAC, respectively. With N2O, values were 52 +/- 14, 23 +/- 5, and 26 +/- 9% of the awake value at 0.83, 1.24, and 1.66 MAC, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1900398 TI - Desflurane is a trigger of malignant hyperthermia in susceptible swine. AB - Desflurane (difluoromethyl 1-fluoro 2,2,2-trifluoroethyl ether: CF2-H-O-CFH-CF3) is a potent inhalation anesthetic agent being investigated for possible clinical use. The authors examined the effects of this agent on normal swine and those from a special breeding program that were considered purebred for susceptibility to malignant hyperthermia (MH). Animals were exposed to 1 or 2 MAC or both doses of desflurane and observed for changes in end-tidal CO2, arterial blood gases, lactate, catecholamines, core temperature, blood pressure, and heart rate. All normal swine tolerated exposure to desflurane without clinical signs of MH, but significant changes in heart rate and blood pressure were noted. In contrast, of six MH susceptible swine tested, two had unequivocal MH reactions to deflurane, defined by significant increases of end-tidal CO2 (greater than 50 mmHg), an increase in PaCO2 (greater than 70 mmHg), a decrease in blood pH (less than 7.30), an increase in blood lactate concentration, and an increase in core temperature. Two other susceptible swine showed equivocal signs of MH but not until desflurane had been administered for 40-60 min. Finally, two other susceptible swine showed no signs of MH after 60 min of exposure to 2 MAC desflurane. These latter four animals all developed episodes of MH immediately after intravenous succinylcholine (2 mg/kg). The increased PaCO2, blood lactate concentrations, and temperature, and the decrease in pH induced by desflurane, were successfully treated with dantrolene and supportive measures. All surviving animals were biopsied 1 to 2 weeks after the exposure to desflurane for in vitro contracture testing to confirm MH susceptibility.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1900397 TI - The response of the canine cerebral circulation to hyperventilation during anesthesia with desflurane. AB - Arterial CO2 tension (PaCO2) is an important factor controlling cerebral blood flow (CBF) and cerebral vascular resistance (CVR) in animals and humans. The normal responsiveness of the cerebral vasculature to PaCO2 is approximately 2 ml.min-1.100 g-1.mmHg-1. This study examined the effect of desflurane, a new volatile anesthetic, on the responsiveness of the cerebral vasculature to changes in PaCO2. Mean arterial pressure (MAP), CBF, CVR, intracranial pressure (ICP), and cerebral metabolic rate for O2 (CMRO2) were measured in five dogs anesthetized with desflurane (0.5-1.5 MAC) at normocapnia (PaCO2 = 40 mmHg) and at two levels of hypocapnia (PaCO2 = approximately 30 and approximately 20 mmHg). Under desflurane anesthesia, similar changes in CBF and CVR occurred with hyperventilation at all MAC levels of desflurane. At 0.5 MAC, CBF decreased significantly, from 81 +/- 6 to 40 +/- 3 ml.min-1.100 g-1 (P less than 0.05, mean +/- SE) when PaCO2 was decreased from 40 to 24 mmHg; i.e., the CBF decreased approximately 2.6 ml.min-1.100 g-1.mmHg-1. At 1.0 MAC desflurane, CBF decreased significantly, from 79 +/- 10 to 43 +/- 5 ml.min-1.100 g-1 with hyperventilation (2.0 ml.min-1.100 g-1.mmHg-1); at 1.5 MAC desflurane, CBF decreased from 65 +/- 6 to 38 +/- 2 ml.min-1.100 g-1 with hyperventilation (1.6 ml.min-1.100 g-1.mmHg-1). Despite the significant decreases in CBF with hyperventilation, there was no significant change in ICP. Dose-dependent decreases in MAP were observed with increasing concentrations of desflurane but were not significantly affected by ventilation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1900399 TI - Capnography in a patient after single lung transplantation. PMID- 1900400 TI - Respiratory response to arm elevation in patients with chronic airflow obstruction. AB - We have shown that patients with chronic airflow obstruction (CAO) complain of disabling dyspnea when performing seemingly trivial tasks with unsupported arms. Surprisingly little is known about the metabolic and ventilatory responses to unsupported upper extremity activity even though some of the muscles of the upper torso and shoulder girdle are used to perform simple and complex everyday tasks as well as partake in ventilation. To determine the effect of simple arm elevation in 20 patients with CAO we studied their lung function, VO2, VCO2, and VE, with arms down at the side (AD), during 2 min with arms extended forward up to shoulder level (AE), and during recovery. To determine the pattern of ventilatory muscle recruitment we also measured endoesophageal (Ppl), gastric (Pg), and transdiaphragmatic (Pdl) pressures. In five of the patients the electromyographic signal (EMG) of the sternocleidomastoid (Sm) muscle was recorded and analyzed in its time domain (amplitude) and power spectrum density (median frequency). Within 30 s of arm elevation VO2, VCO2, and VE rose and remained elevated for 1 min after the arms were lowered. The increase in VE resulted from increases in respiratory rate and minimal rise in tidal volume (VT). With AE, FEV1 decreased by 5% (p less than 0.02) but FRC increased by 2% (p less than 0.05). Peak inspiratory pressure (Pimax) dropped from 54 +/- 4 to 48 +/ 4 cm H2O (p less than 0.005); Pdimax remained unchanged. Immediately after raising the arms Pgi, inspiratory swing in Pdi (delta Pdi), end-expiratory Ppl, and end-expiratory Pg increased significantly.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1900401 TI - Decreased oxyhemoglobin affinity in patients with sleep apnea syndrome. AB - Oxyhemogloblin affinity (P50 at pH 7.4, PaCO2 = 40 mm Hg, temperature = 37 degrees C) and 2,3-DPG concentration were assessed in 15 nonsmokers (14 men and one woman 46 to 63 yr of age) with sleep apnea syndrome (SAS) and in 10 normal subjects (eight men and two women 22 to 48 yr of age). In patients with SAS, mean nocturnal apnea index was 46 +/- 20/h, and mean nocturnal SO2 was 86 +/- 6% versus 94.6 +/- 1.8% during the daytime. Daytime mean P50 of the patients was 28.5 +/- 1.2 mm Hg versus 27.1 +/- 0.3 mm Hg in the normal subjects (p less than 0.05). Daytime mean 2.3-DPG was 1.23 +/- 0.25 moles DPG/mole hemoglobin versus 0.80 +/- 0.15 (p less than 0.05). Significant correlations were found in patients between P50 and mean nocturnal SO2 (r = -0.62, p less than 0.01) and between P50 and 2,3-DPG (r = 0.68, p less than 0.01). The measurements were repeated in five patients after surgical or positive-pressure treatment. P50 and 2,3-DPG both decreased and returned to normal values. In conclusion, the oxyhemoglobin dissociation curve is shifted to the right in patients with SAS and there is an increase in 2,3-DPG. These could be protective mechanisms against the development of polycythemia, pulmonary hypertension, and cor pulmonale. PMID- 1900402 TI - Inhibition of cyclooxygenase metabolite production attenuates ischemia reperfusion lung injury. AB - We investigated if cyclooxygenase metabolites of arachidonic acid were involved in ischemia-reperfusion lung injury by determining if inhibition of their production attenuated the injury. Isolated rat lungs were perfused with physiologic salt solution osmotically stabilized with Ficoll until circulating blood elements were not detected in lung effluent. Ischemia was induced by stopping ventilation and perfusion for 90 min. Lung ventilation and perfusion were then resumed. Ischemia-reperfusion resulted in the production of prostacyclin and thromboxane assessed by lung effluent and tissue measurements of their respective stable metabolites, 6-keto-PGF1 alpha thromboxane B2 (TxB2). In contrast, prostaglandin F2 alpha did not increase. Ischemia-reperfusion also caused lung injury as assessed by increased lung 125I-BSA accumulation compared with nonischemic control lungs. Addition of the cyclooxygenase inhibitors, indomethacin, or flubiprofen to the lung perfusate before and after ischemia inhibited lung injury as well as the production of 6-keto-PGF1 alpha and TxB2. Addition of a thromboxane synthetase inhibitor (U 63557A) reduced lung injury as well as TxB2 formation without affecting the production of 6-keto-PGF1 alpha. The attenuation of lung injury was not explained by direct H2O2 removal by indomethacin, flubiprofen, or U 63557A because the concentrations of the inhibitors used in the isolated lung experiments did not remove exogenously added H2O2 from buffer in vitro. We conclude that cyclooxygenase metabolites of arachidonic acid are involved in ischemia-reperfusion injury to isolated rat lungs. PMID- 1900403 TI - Nasal spray desmopressin (DDAVP) for mild hemophilia A and von Willebrand disease. AB - OBJECTIVE: To evaluate the effect of a nasal spray preparation of desmopressin (DDAVP) on levels of factor VIII activity, ristocetin cofactor activity, and von Willebrand antigen as well as the length of bleeding time in patients with mild hemophilia A and von Willebrand disease; to determine whether effective hemostatic levels can be attained; and to compare the effect of this spray with that of standard intravenous desmopressin treatment. DESIGN: Before-and-after trial in patients known to respond to intravenous desmopressin. SETTING: Regional, comprehensive, hemophilia diagnosis and treatment center. PATIENTS: A total of 22 patients, including 11 patients with von Willebrand disease, 8 patients with mild hemophilia A, and 3 symptomatic hemophilia carriers. INTERVENTIONS: Patients were infused with desmopressin, 0.3 micrograms/kg body weight. At least 1 week later, they were taught to self-administer desmopressin nasal spray, 150 micrograms to each nostril. MEASUREMENTS: In patients with hemophilia, the level of factor VIII activity was measured; in patients with von Willebrand disease, levels of factor VIII activity, ristocetin cofactor activity, and von Willebrand antigen as well as bleeding time were measured before and after each administration of desmopressin. MAIN RESULTS: Desmopressin, when administered intravenously or intranasally, elevated levels of factor VIII, ristocetin cofactor, and von Willebrand antigen in both mildly hemophiliac patients and patients with von Willebrand disease when compared with baseline measures (P less than 0.05). Factor VIII levels adequate for hemostasis were achieved by 82% of the hemophiliac patients. An abnormal bleeding time was corrected in the majority (62%) of patients with von Willebrand disease. CONCLUSION: A nasal spray preparation of desmopressin apparently was effective both in treating bleeding episodes and when used prophylactically for minor surgical procedures in several patients. PMID- 1900404 TI - NIH conference. Diagnosis and management of asymptomatic primary hyperparathyroidism: consensus development conference statement. AB - Endocrinologists, surgeons, radiologists, epidemiologists, and primary health care providers convened to address both indications for surgery in asymptomatic patients with hyperparathyroidism as well as how patients who do not have surgery should be monitored and managed to minimize the risk for complications. The National Institutes of Health Consensus Development Conference Panel concluded that a diagnosis of hyperparathyroidism is established by showing persistent hypercalcemia and an elevated serum parathyroid hormone concentration; that the current and acceptable treatment for hyperparathyroidism is surgery; that the diagnosis of hyperparathyroidism in an asymptomatic patient does not in all cases mandate referral for surgery; that conscientious surveillance may be justified in patients whose calcium levels are only mildly elevated and whose renal and bone status are close to normal; and that preoperative localization in patients without previous neck operation is rarely indicated and has not proved to be cost effective. PMID- 1900405 TI - Clinical aspects of 100 patients with Kawasaki disease. AB - We report 101 episodes of Kawasaki disease in 100 patients seen over a 12 year period. A total of 35 patients had cardiac involvement ranging from pericardial effusion to coronary artery aneurysms with ischaemic complications, which resulted in death in one patient. Laboratory investigations showed leucocytosis, thrombocytosis, and a raised erythrocyte sedimentation rate to be common features and the first two variables were significantly associated with cardiac involvement. Treatment regimens changed over the study period. Aspirin was used in most patients often in conjunction with dipyridamole and from 1986 intravenous immunoglobulin was given routinely to those patients seen early in the illness. Additional therapeutic measures in individual patients included prostacyclin, heparin, streptokinase, and plasma exchange/exchange transfusion. Attention is drawn to the uncertainity of the long term cardiovascular consequences in the light of adults reported with premature atherosclerotic lesions of similar appearance to those seen in Kawasaki disease. PMID- 1900406 TI - Antiendothelial cell antibodies detected by a cellular based ELISA in Kawasaki disease. AB - Kawasaki disease is an acute vasculitic illness of childhood associated with significant morbidity and mortality. A cellular based enzyme linked immunosorbent assay (ELISA) was used to demonstrate the presence of antiendothelial cell antibodies in sera from children with Kawasaki disease. Twenty one of 32 patients with Kawasaki disease had raised IgM antibody titres and four had raised IgG antiendothelial antibody titres. There was a significant difference in the IgM antiendothelial cell antibody titres when comparing the patients with normals and febrile controls. The antibody titre paralleled the disease activity in patients studied serially. There was no relative increase in binding of antiendothelial cell antibodies after cytokine stimulation. These findings may be of importance in further research into the understanding of mechanisms involved in this and other forms of vasculitis in man. PMID- 1900407 TI - Sucking on the 'emptied' breast: non-nutritive sucking with a difference. AB - A simple method to promote the use of human milk and subsequent breast feeding in low birthweight infants was evaluated in 32 babies. In the 'intervention' group (n = 16; mean (SD) weight 1559 (228) g and length of gestation 33.2 (1.8) weeks), infants were allowed to suckle at the breast when their general condition permitted after as much milk as possible had been expressed, and were then given the full required feeds by tube. Full breast feeding was started as soon as the infant could suck adequately. Sixteen control infants (mean (SD) weight 1605 (198) g and length of gestation 34.1 (2.4) weeks), were breast fed in the conventional manner only after it had been established that they could suck well; until then they received all their feeds by tube. After discharge the mean (SD) periods of exclusive and total breast feeding were longer in the group that had received the intervention (3.7 (1.3) and 5.1 (2.2) months, respectively) than among the controls (1.9 (0.6) and 3.3 (1.9) months, respectively). This 'intervention' method helps to promote milk formation, provides sucking experience for low birthweight infants without interfering with their nutritional intake and consequent weight gain, and encourages subsequent breast feeding with its well recognised advantages. PMID- 1900408 TI - Malignant hypercalcemia. The choice of therapy. PMID- 1900409 TI - Home care for the elderly. The new institution. PMID- 1900410 TI - Treatment of hypercalcemia of malignancy with intravenous etidronate. A controlled, multicenter study. The Hypercalcemia Study Group. AB - In a prospective, randomized, double-blind, multicenter study, 202 patients with cancer from 19 medical centers were treated for hypercalcemia of malignancy with daily intravenous infusions of etidronate disodium (136 patients) or saline alone (66 patients) for 3 consecutive days. Patients also received up to 3.25 L of saline daily during the treatment period. Of 157 patients for whom data could be evaluated for efficacy, 63% (72/114) of etidronate-treated and 33% (14/43) of saline-treated patients had a normalization of total serum calcium levels. When serum calcium levels were adjusted for albumin (147 assessable patients), 24% of the etidronate- and 7% of the saline-treated patients responded to treatment. No serious side effects or treatment-related deaths occurred. When accompanied by adequate hydration and diuresis, intravenous etidronate was safe and more effective than hydration and diuresis alone in controlling hypercalcemia of malignancy. PMID- 1900411 TI - Clinical significance of low serum thyrotropin concentration by chemiluminometric assay in 85-year-old women and men. AB - The prevalence and causes of low serum thyrotropin concentration were studied in 886 individuals at age 85 years (601 women and 285 men). All participants were subject to detailed clinical and biochemical evaluation, including determination of serum thyrotropin and free thyroxine concentrations by chemiluminometric assays. Samples with thyrotropin concentrations below 0.20 mU/L or above 6.0 mU/L and/or free thryoxine concentrations above 22.0 pmol/L were selected for further assays. These selected individuals were followed-up during 3 years. Of 18 individuals without thyroid hormone treatment who had thyrotropin concentrations less than 0.20 pmol/L (13 below 0.10 pmol/L), only two were proved to be hyperthyroid; in another three, hyperthyroidism could not be excluded. The results indicate that most elderly individuals with low serum thyrotropin concentrations are not hyperthyroid and that abnormal thyroxine-binding globulin (in conjunction with drug treatment or nonthyroidal illness) is not a common cause of low thyrotropin concentration. PMID- 1900413 TI - Successful treatment of pure myopathy, associated with complex I deficiency, with riboflavin and carnitine. AB - We describe a 6-year-old boy who presented with progressive muscle weakness. Additional investigations revealed the existence of a myopathy and a pure motor neuropathy. Biochemical studies in muscle tissue showed a defect of NADH dehydrogenase (complex I). The patient dramatically improved on treatment with riboflavin and L-carnitine. Seven months after the start of the treatment, complex I activity was determined again and appeared to be normalized. Normalization of the enzymatic defect at this level has not been reported before. We provide a survey of nine patients with pure myopathy, associated with complex I deficiency and onset of symptoms in childhood. PMID- 1900412 TI - Evaluation of relationships between avian paramyxoviruses isolated from birds of the family Columbidae. AB - The prototype virus for the PMV-7 serotype of avian paramyxoviruses, PMV-7 dove Tennessee/4/75 (Tn 4) and five other isolates obtained from birds of the Columbidae family, which had been shown to be distinct from PMV-1 serotype, were tested for antigenic relationships between themselves and to other avian paramyxoviruses. By serological tests and analysis of structural polypeptides the viruses appeared to be distinct from other avian paramyxoviruses. One isolate appeared to be very closely related to Tn/4. Three other isolates showed only minor relationships to these two but were very closely related to each other. However, the sixth virus, pigeon Japan/Otaru/76, showed high levels of homology in haemagglutination inhibition tests and at least one line of identity in immunodoublediffusion tests with all five of the other isolates. PMID- 1900414 TI - Tissue plasminogen activator and cardiopulmonary bypass for massive pulmonary embolus. AB - Massive pulmonary embolus resulting in cardiac arrest and doubtful cerebral status may result in indecision as to whether to proceed to pulmonary embolectomy, especially if there is continuing cardiorespiratory instability. A case is reported on the use of fibrinolysis and cardiopulmonary bypass, allowing for the cerebral status of the patient to become more clearly defined while maintaining cardiopulmonary stability and attempting to treat the underlying pathological process. PMID- 1900415 TI - Effects of water immersion on cardiac output of lean and fat male subjects at rest and during exercise. AB - To investigate the combined effect of water immersion (WI) and lean body mass on cardiac output (Q), 12 healthy young men, 6 lean (fat less than 9%) and 6 fat (fat greater than 18%), were studied at rest and during steady state exercise approximating 30-40% Vo2 max under three experimental conditions. There were on land at 24 degrees C (LND), and immersed in water at 33-34 degrees C to hip level (HIP), and to the xiphoid (XIP). Metabolic measures were determined during 30-s periods from the average breath measurements. Mixed venous PCO2 (PVCO2) was estimated using rebreathing equilibration technique. Cardiac output was calculated by the indirect Fick's principle. In the lean individuals the average Q rose from a resting value of 5.43 +/- 0.43 (LND) to an exercise value of 7.25 +/- 0.40 L/min (XIP), and from resting value of 5.62 +/- 0.40 to an exercise 6.47 +/- 0.5 L/min in the fat individuals. During exercise, the associated increase in Q with increasing WI was significantly (p less than 0.05) higher compared with the land experiments. Inspection of the mean profile corresponding to this increase indicated that an increase in the level of immersion results in a significant (p less than 0.05) increase in the average Q for the lean group. For the fat group, the average Q was significantly (p less than 0.05) larger only at XIP level. At rest, heart rate dropped from 67 +/- 3.36 (LND) to 60 +/- 4.13 (XIP), and from 79 +/- 3.73 to 73 +/- 4.10 BPM for the lean and fat group, respectively. MANOVA analysis showed a significant (p less than 0.05) interaction between WI and group membership, indicating that the effect of WI is significantly different between the two groups. These data indicate that the change in central blood volume with WI depends, in part, on the lean mass of the body. PMID- 1900416 TI - Reoxygenation-dependent decrease in mitochondrial NADH:CoQ reductase (Complex I) activity in the hypoxic/reoxygenated rat heart. AB - Reoxygenation of the hypoxic myocardium results in a number of processes, including an O2-dependent increase in total tissue Ca2+ and cell lysis in which mitochondrial electron transport plays a key role. In the present study we have isolated mitochondria from perfused rat hearts subjected to hypoxia and found no change in their respiratory function relative to controls. In contrast, mitochondria isolated immediately after reoxygenation of hypoxic-perfused hearts exhibited a specific and significant decrease in NADH:CoQ reductase (Complex I; EC 1.6.5.3) activity, as measured both polarographically and spectrophotometrically. Isolated cardiomyocytes subjected to a similar protocol of hypoxia/reoxygenation also exhibited a specific decrease in Complex I activity. Myocardial perfusion with media containing Ruthenium Red protected against the reoxygenation-dependent loss of Complex I activity. These observations taken together suggest that mitochondrial Ca2+ uptake on reoxygenation is implicated in the mechanism of the specific loss of Complex I activity. PMID- 1900417 TI - Regulation of Cu,Zn superoxide dismutase with copper. Caeruloplasmin maintains levels of functional enzyme activity during differentiation of K562 cells. AB - K562 cells, a human erythroleukaemic cell line blocked for differentiation, commit towards erythrocytes when exposed to haemin (20 microM). The cells synthesize fetal haemoglobins and show site-specific binding of caeruloplasmin, a plasma copper protein. These events are set into motion by haemin. On the assumption that the binding of caeruloplasmin could reflect a greater need for copper, we sought to determine whether the transfer of 67Cu from caeruloplasmin was accelerated in haemin-induced compared with non-induced K562 cells. Cu,Zn superoxide dismutase (CuZnSOD) was the recipient. Haemin induction caused the K562 cells to lose CuZnSOD activity. By 96 h, the level of SOD activity was less than 60% of that of non-induced cells. The loss was confined entirely to the CuZn form, MnSOD activity staying essentially unchanged. Although CuZnSOD activity declined with the haemin induction, the incorporation of [4,5-3H]lysine into immunoprecipitable CuZnSOD protein was unaffected. There was also no change in CuZnSOD mRNA concentration in haemin-induced cells. Thus a loss of enzyme did not correlate with a decline in the synthesis de novo of CuZnSOD protein. When 48 h induced cells were transferred to a medium supplemented with 0.2 microM caeruloplasmin, CuZnSOD activity was restored to control levels in 24 h. Caeruloplasmin also stimulated the incorporation of [3H]lysine into immunoprecipitable CuZnSOD protein. Caeruloplasmin addition may have affected a post-translational regulatory site for CuZnSOD biosynthesis, possibly by providing copper for the newly synthesized enzyme. PMID- 1900420 TI - Molecular cloning and primary structure of squid (Loligo forbesi) rhodopsin, a phospholipase C-directed G-protein-linked receptor. AB - The sequence of squid (Loligo forbesi) rhodopsin was determined by protein and cDNA sequencing. The protein has close similarity to octopus rhodopsin, having an N-terminal region (residues 1-340) which resembles other guanine-nucleotide binding protein (G-protein)-linked receptors and a repetitive proline-rich C terminus (residues 340-452). Comparison of the sequence of squid rhodopsin with those of other members of the G-protein-linked receptor superfamily reveals features which we predict to have both structural and functional importance. PMID- 1900418 TI - The pro-polypeptide of von Willebrand factor is required for the formation of a functional factor VIII-binding site on mature von Willebrand factor. AB - We have established that a recombinant von Willebrand Factor (vWF) mutant (vWFdelpro) that lacks the propolypeptide, in contrast with mature wild-type vWF, with which it is identical in terms of primary amino acid sequence, is not able to form a complex with Factor VIII. Wild-type vWF (flvWF) and vWFdelpro were expressed in AtT-20 cells. Under the culture conditions employed, completely processed multimerized flvWF and dimeric vWFdelpro were secreted into the medium. FlvWF and vWFdelpro were compared for their Factor VIII-binding properties in two distinct assay systems. In a direct binding assay, purified human Factor VIII was shown to bind to flvWF that had been immobilized on the surface of microtitre wells by using an anti-vWF monoclonal antibody. In contrast, Factor VIII did not bind to immobilized vWFdelpro. In a competition assay, fluid-phase flvWF appeared to inhibit efficiently the binding of Factor VIII to immobilized vWF isolated from plasma, whereas vWFdelpro did not influence Factor VIII binding. From these observations, it is argued that the pro-polypeptide serves an essential role in the post-translational processes that lead to the expression of a functional Factor VIII-binding site on the mature vWF subunit. PMID- 1900421 TI - Possible secondary structure in plant and yeast beta-glucanase. AB - Circular-dichroism spectra of a barley 1,3-beta-glucanase were analysed by two methods. The combined results predict 36-40% helix and 15-18% beta-structure in the protein. Prediction of secondary-structural features on the basis of amino acid sequence information yielded overall helix and beta-structure contents of 37% and 19% respectively. Comparison of the predicted structural elements along the barley 1,3-beta-glucanase with those of three related plant glucanases and a yeast glucanase suggest a close similarity in secondary structure among the five proteins. Consideration is given to the potential importance of certain amino acids which are conserved in these five glucanases. PMID- 1900419 TI - alpha-L-iduronidase in normal and mucopolysaccharidosis-type-I human skin fibroblasts. AB - alpha-L-Iduronidase synthesis and maturation were analysed in fibroblasts from normal controls and from alpha-L-iduronidase-deficient mucopolysaccharidosis-type I (MPS-I) patients. Fibroblasts were radiolabelled with [3H]leucine and alpha-L iduronidase was isolated from cell lysates or culture medium by monoclonal antibody affinity chromatography. Pulse-chase labelling of normal control fibroblasts showed that alpha-L-iduronidase was synthesized as an 81 kDa precursor and processed within 24 h via intermediates of 76 kDa and 70 kDa to a 69 kDa species. The incorporation of radiolabel into alpha-L-iduronidase in fibroblasts from three of four MPS-I patients was at levels that were either very low or undetectable. Fibroblasts from one MPS-I patient, however, exhibited levels of incorporation of radiolabelled amino acid into alpha-L-iduronidase similar to those shown by normal control fibroblasts, despite having undetectable alpha-L-iduronidase enzyme activity. The maturation of alpha-L-iduronidase in fibroblasts from this patient was delayed compared with normal controls and showed accumulation of the 76 kDa intermediate, as well as the major 69 kDa, form of the enzyme. PMID- 1900422 TI - Prevalence and persistence of polyagglutinable Pseudomonas aeruginosa in isolates from cystic fibrosis patients. AB - During the 17 years from 1972 to 1988 1010 Pseudomonas aeruginosa isolates from sputum samples of 183 cystic fibrosis patients attending the Danish Cystic Fibrosis Centre at Rigshospitalet were serogrouped and phage typed. The patients were chronically infected with Pseudomonas aeruginosa (range of duration of infection: 1-17 years). They attended the Centre monthly and since 1976 all had been hospitalized for 14 days every three months. The number of patients with Pseudomonas aeruginosa infection increased from 29 to 123 during the period 1972 to 1988 and the number of isolates typed ranged from 14 to 197 a year. About half of the patients had one to five monoagglutinable isolates before they had polyagglutinable isolates. The prevalence of polyagglutinable isolates each year increased during the observation period (range: 24% to 88%). In all, three quarters of the patients had polyagglutinable isolates in their last typed sample. During the 17-year period 81% of the patients harboured polyagglutinable isolates. 77% of these patients, however, were for periods colonized with monoagglutinable isolates (0-3, 0-6, 0-1, 0-2 (including 0-2, 0-5, 0-2/5 due to cross-reactions between 0-2 and 0-5) and 0-9 were most prevalent) either alone or concurrent with polyagglutinable isolates, whereas 5% harboured polyagglutinable isolates exclusively during the whole observed period of infection. Polyagglutinable isolates with a short phage pattern were more frequent than those with a long phage pattern during the entire period from 1972 to 1988, and the prevalence increased during the period. Twenty-eight percent of the patients had a persistent phage pattern for an average of seven years in spite of change of serogroup. Twenty-seven percent of the patients had a persistent monoagglutinable serogroup and phage pattern for an average of eight years. The increasing prevalence and persistence of polyagglutinable strains correlate with the improved survival of the patients and thereby with the increased duration of the infection. The reason for this is discussed. PMID- 1900423 TI - Pulmonary dendritic cells: sentinels of lung-associated lymphoid tissues. PMID- 1900424 TI - Accessory cells of the lung. I. Interferon-gamma increases Ia+ dendritic cells in the lung without augmenting their accessory activities. AB - Dendritic cells are specifically adapted to provide accessory signals for the growth of T lymphocytes. Ia+ dendritic cells are present within the normal lung; however, little is known concerning their regulation in vivo. Interferon-gamma (IFN-gamma) is a proinflammatory lymphokine that augments the expression of Ia antigens and promotes the accessory activities of a variety of cells. In order to determine whether IFN-gamma regulates pulmonary dendritic cells in vivo, Lewis rats were injected intraperitoneally with recombinant murine IFN-gamma (2 x 10(5) U/rat/day) or with buffered saline for 5 consecutive days. Following sacrifice, the lungs were excised, and the distribution and number of Ia (OX-6)+ cells was determined in situ. Dendritic cells were localized in the mucosal lining of the tracheobronchial tree, in pulmonary capillaries, as well as in the alveolar septal interstitium and subjacent to the pleural surfaces. IFN-gamma yielded a specific increase in Ia+ dendritic cells in alveolar septa and in pulmonary airways. Purified Ia+ dendritic cells from enzymatic digests of lung were excellent accessory cells for the proliferative responses of both antigen-primed and naive T lymphocytes. IFN-gamma did not, however, further augment the expression of Ia antigens or the accessory activities of pulmonary dendritic cells. These results suggest that IFN-gamma may promote pulmonary T cell-mediated inflammatory responses in vivo by increasing the number of Ia+ dendritic accessory cells in the lung. PMID- 1900425 TI - Growth inhibition of Mycobacterium avium complex in human alveolar macrophages by the combination of recombinant macrophage colony-stimulating factor and interferon-gamma. AB - The reservoir of Mycobacterium avium complex (MAC) during human infection is the mononuclear phagocyte. In these studies, the ability of certain macrophage-active cytokines to affect MAC growth in human alveolar macrophages was evaluated. Neither recombinant interferon-gamma (2 x 10(2) to 10(3) U/well of 5 x 10(5) cells) nor recombinant macrophage colony-stimulating factor (20 to 50 ng/well), when tested alone, exhibited a consistent ability to induce macrophage targets to inhibit the growth of a clinical strain of MAC serovar 4. However, the combination of these cytokines (1 to 50 ng macrophage colony-stimulating factor + 10(3) U interferon per well) was remarkably effective in diminishing replication of MAC in all experiments. These cytokines were also able to induce alveolar macrophages to restrict MAC growth even though cells were obtained from several individuals with acquired immunodeficiency syndrome (AIDS) or from normal donors and infected in vitro with the human immunodeficiency virus type 1. The effect of this cytokine combination was not abrogated by 10(4) neutralizing U/ml of anti tumor necrosis factor-alpha antibody. Rather, the combination of interferon-gamma and macrophage colony-stimulating factor appeared to activate intrinsic macrophage mechanisms for restricting MAC growth and deserves further study to determine the potential value of this cytokine combination in the treatment of human infection. PMID- 1900426 TI - Alkylating agent hypersensitivity in poly(adenosine diphosphate-ribose) polymerase deficient cell lines. AB - Starting with the V79 cell line, two poly(ADP-ribose) polymerase deficient mutants, designated ADPRT 54 and ADPRT 351, had been shown to be hypersensitive to x- and UV-irradiation and to topoisomerase I inhibitors but to be resistant to topoisomerase II inhibitors (Chatterjee, S.; Cheng, M. F.; Berger, N. A. Hypersensitivity to clinically useful alkylating agents and radiation in poly(ADP ribose) polymerase-deficient cell lines. Cancer Commun. 2:401-407;1990). We now report that these mutants were hypersensitive to a series of different alkylating agents, including alkylsufonates, alkylnitrosoureas, and nitrosoguanidine. In addition, they were hypersensitive to the UV-mimetic agent 4-nitroquinoline-1 oxide. Our findings provide strong evidence that poly(ADP-ribose) polymerase was involved in the repair of alkylating agent induced DNA damage as well as in the damage induced by UV- and x-irradiation and radiomimetic agents. The poly(ADP ribose) polymerase deficient cell lines showed a marked decrease in the shoulder region of their survival curves, suggesting that poly(ADP-ribose) polymerase was involved in the repair of alkylating agent induced sublethal damage. PMID- 1900427 TI - Swainsonine stimulation of the proliferation and colony forming activity of murine bone marrow. AB - Swainsonine, an indolizidine alkaloid, was recently reported to exhibit both antineoplastic and immunomodulatory activities (Humphries, M.J.; Olden, K. Asparagine-linked oligosaccharides and tumor metastasis. Pharmacol. Ther. 44:85 105; 1989). In this study, we show that systemically administered swainsonine promoted the proliferation of murine bone marrow (BM) cells. Animals that received swainsonine intravenously exhibited a significant increase (approximately 5-10 fold) in BM cellularity, engraftment efficiency, and colony forming unit activity using in vitro or in vivo assays. BM cells derived from swainsonine-treated animals or treated with swainsonine in vitro also exhibited a 4-5 fold increase in [3H]-thymidine incorporation, suggesting that a larger fraction of the cells was in the S-phase of the cell cycle. This provides the first evidence that swainsonine, which stimulates the production of cytokines by cells of the immune system, promoted the proliferation of BM progenitor cells. These results suggest that swainsonine could prove valuable in patients undergoing intensive chemoradiotherapy or autologous BM transplantation by decreasing or possibly eliminating leukopenia or myelosuppression often associated with these procedures; it may also be a useful probe to investigate the mechanism of normal hematopoieses. PMID- 1900428 TI - Follicle stimulating hormone levels as a predictor of recovery of spermatogenesis following cancer therapy. AB - Infertility, both temporary and permanent, is a well-recognized complication of certain cancer treatments. The main objective of this study was to determine whether recovery of fertility in male patients, could be predicted by monitoring changes in serum follicle stimulating hormone (FSH) levels. Twenty male patients participated in the study. Sperm counts and serum FSH levels were measured before, during and after treatment. Azoospermia was universal in all 20 patients during the first year, with significantly raised FSH in almost all the patients. Reduction of FSH levels during the second year was frequently followed by recovery of spermatogenesis. Patients in whom the FSH did not fall during the second year were highly unlikely to regain fertility. PMID- 1900429 TI - Structural and ligand-binding properties of a truncated form of Bacillus anthracis adenylate cyclase and of a catalytically inactive variant in which glutamine substitutes for lysine-346. AB - A truncated, 541-residue-long, Bacillus anthracis adenylate cyclase was expressed in Escherichia coli. The purified protein (CYA 62) exhibited catalytic and CaM binding properties identical with those of the wild-type enzyme secreted by B. anthracis. The analysis of the secondary structure of the CYA 62 protein by Fourier transform infrared spectroscopy and circular dichroism revealed the dominance of beta-type structure. The protein shows a relatively low thermal stability with the midpoint denaturation temperature at 45 degrees C. A catalytically inactive variant of CYA 62 in which Gln substituted for Lys-346 (CYA 62 K346Q) was comparatively analyzed for its secondary structure and thermal stability, as well as ligand-binding properties with fluorescent derivatives of ATP and calmodulin. The K346Q variant of CYA 62 has a similar secondary structure and comparable calmodulin binding properties to those of the parent protein and exhibits only slightly reduced thermal stability (the apparent midpoint denaturation temperature is at 43 degrees C). Despite these similarities, the binding of 3'-anthraniloyl-2'-deoxy-ATP (a fluorescent ATP analogue) to the modified protein is severely impaired, from which we conclude that the prime function of Lys-346 in the wild-type enzyme from B. anthracis is to ensure tight binding of the nucleotide substrate to the active site. PMID- 1900430 TI - Localization in the Golgi apparatus of rat liver UDP-Gal:glucosylceramide beta 1- --4galactosyltransferase. AB - The presence and subcellular localization of UDP-Gal:glucosylceramide beta 1--- 4galactosyltransferase (GalT-2) was investigated in rat liver. For this purpose, purified Golgi apparatus, endoplasmic reticulum, and plasma membrane fractions were prepared from the liver and used as the enzyme source for detecting GalT-2. A pure Golgi apparatus, highly enriched in many glycosyltransferases, was the only fraction where GalT-2 was measurable. The reaction product formation rate under appropriate assay conditions, which requires high detergent concentration and Mn2+, was low but comparable with that of other glycosyltransferases. The product formation was stimulated by exogenously added acceptor GlcCer, donor UDP Gal, and Golgi protein. The reaction product was a single spot that was identified by chromatographic behavior, sensitivity to beta-galactosidase, and permethylation studies as Gal beta 1----4Glc beta 1----1'Cer (lactosylceramide). A metabolic experiment, performed by determining the glycosphingolipids which became radioactive in the above subcellular fractions prepared from the liver of animals treated with glucose-labeled glucosylceramide, further indicated that the in vivo glycosylation of glucosylceramide takes place in the Golgi apparatus. PMID- 1900431 TI - Tissue plasminogen activator has an O-linked fucose attached to threonine-61 in the epidermal growth factor domain. AB - An unusual type of glycosylation has been observed for tissue plasminogen activator (t-PA). The monosaccharide fucose is glycosidically linked to threonine 61 in the epidermal growth factor region of t-PA. The presence of O-linked fucose was demonstrated by carbohydrate analysis and mass spectrometry of tryptic and chymotryptic peptides that contain this site. The susceptibility of the fucose residue to alpha-fucosidase indicated that it was in the alpha-anomeric configuration. Fucosylation of threonine-61 was observed in t-PA isolated from the Bowes melanoma cell line and from recombinant expression systems using Chinese hamster ovary or human embryonic kidney cells. Fucosylation of the homologous residue in prourokinase has also been reported recently. Our results indicate that this novel type of glycosylation may be common to the epidermal growth factor domains found in coagulation and fibrinolytic proteins and, therefore, suggest that the modification may have functional significance. PMID- 1900432 TI - Dissociation kinetics of bivalent ligand-immunoglobulin E aggregates in solution. AB - We study the dissociation of preformed bivalent ligand-bivalent receptor aggregates in solution, where the ligand is a symmetric bivalent hapten with two identical 2,4-dinitrophenyl (DNP) groups and the receptor is a fluorescein labeled monoclonal anti-DNP IgE. We promote dissociation in two ways: by the addition of high concentrations of a monovalent hapten that competes for IgE binding sites with the bivalent hapten and by the addition of high concentrations of unlabeled IgE that binds almost all ligand binding sites that dissociate from labeled IgE. We investigate both theoretically and experimentally the two types of dissociation and find them to be quite different. Theory predicts that their kinetics will depend differently on the fundamental rate constants that characterize binding and aggregation. Using monovalent ligand to promote dissociation, we find that the fraction of labeled IgE sites bound to bivalent ligand decays with a slow and fast component. The fast decay corresponds to the dissociation of a singly bound DNP hapten. The interpretation of the slow decay depends on the detailed way in which ligand-receptor aggregates break up. We show that one possible explanation of these data is that small stable rings form before the addition of monovalent ligand. Other possible explanations are also presented. PMID- 1900433 TI - Interaction of the tRNA(Phe) acceptor end with the synthetase involves a sequence common to yeast and Escherichia coli phenylalanyl-tRNA synthetases. AB - Modified lysines resulting from the cross-linking of the 3' end of tRNA(Phe) to yeast phenylalanyl-tRNA synthetase (an enzyme with an alpha 2 beta 2 structure) have been characterized by sequencing the labeled chymotryptic peptides that were isolated by means of gel filtration and reversed-phase chromatography. The analysis showed that Lys131 and Lys436 in the alpha subunit are the target sites of periodate-oxidized tRNA(Phe). Mutant protein with a Lys----Asn substitution established that each lysine contributes to the binding of the tRNA but is not essential for catalysis. The major labeled lysine (K131) belongs to the sequence IALQDKL (residues 126-132), which shares three identities with the peptide sequence ADKL found around the tRNAox-labeled Lys61 in the large subunit of Escherichia coli phenylalanyl-tRNA synthetase [Hountondji, C., Schmitter, J. M., Beauvallet, C., & Blanquet, S. (1987) Biochemistry 26, 5433-5439]. PMID- 1900434 TI - Function of serine-52 and serine-80 in the catalytic mechanism of Escherichia coli aspartate transcarbamoylase. AB - Carbamoyl phosphate is held in the active site of Escherichia coli aspartate transcarbamoylase by a variety of interactions with specific side chains of the enzyme. In particular, oxygens of the phosphate of carbamoyl phosphate interact with Ser-52, Thr-53 (backbone), Arg-54, Thr-55, and Arg-105 from one catalytic chain, as well as Ser-80 and Lys-84 from an adjacent chain in the same catalytic subunit. In order to define the role of Ser-52 and Ser-80 in the catalytic mechanism, two mutant versions of the enzyme were created with Ser-52 or Ser-80 replaced by alanine. The Ser-52----Ala holoenzyme exhibits a 670-fold reduction in maximal observed specific activity, and a loss of both aspartate and carbamoyl phosphate cooperativity. This mutation also causes 23-fold and 5.6-fold increases in the carbamoyl phosphate and aspartate concentrations required for half the maximal observed specific activity, respectively. Circular dichroism spectroscopy indicates that saturating carbamoyl phosphate does not induce the same conformational change in the Ser-52----Ala holoenzyme as it does for the wild type holoenzyme. The kinetic properties of the Ser-52----Ala catalytic subunit are altered to a lesser extent than the mutant holoenzyme. The maximal observed specific activity is reduced by 89-fold, and the carbamoyl phosphate concentration at half the maximal observed velocity increases by 53-fold while the aspartate concentration at half the maximal observed velocity increases 6 fold.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1900435 TI - Kinetic study on the effect of pH on the melanin biosynthesis pathway. AB - This paper deals with the quantitative description of the regulatory effect of pH on the oxidation pathway of L-dopa to yield melanins. Tyrosinase catalyzes the oxidation by molecular oxygen of L-dopa to o-dopaquinone, which evolves non enzymatically through a branched pathway with cyclization or hydroxylation reactions. The production of several quinones and semiquinones in the pathway has also been reported. The intermediates of the hydroxylation branch have been identified and the corresponding rate constants have been determined. These compounds, such as have been detected in melanosomes and in tumoral cells, have great cytotoxic power and could have physiological significance in acidic media. PMID- 1900436 TI - Eukaryotic initiation factor 5A: the molecular form of the hypusine-containing protein from human erythrocytes. AB - Eukaryotic initiation factor 5A (eIF-5A, formerly known as eIF-4D) purified from human erythrocytes has been found to have a monomeric molecular weight between 17,500 and 18,000. In this study, using exclusion chromatography and analytical ultracentrifugation, we demonstrate that eIF-5A normally exists as a dimer in solution and appears to be capable of undergoing reversible association to form higher polymers. PMID- 1900437 TI - Cell-type-specific transcription in yeast. PMID- 1900438 TI - A limited number of Bacillus subtilis strains carry a tetracycline-resistance determinant at a site close to the origin of replication. AB - Several strains of Bacillus subtilis, e.g., 168 derivatives and R, were found to carry a single copy of a tetracycline-resistance (TcR) determinant (named tetBS908) at a site close to the origin of replication on the chromosome. This gene is highly homologous (80% identical) to the TcR determinant of plasmids widely dispersed among aerobic spore-forming bacilli. B. subtilis RM125 (168 strain) transformants which carry a varying number of tetBS908 sequences in a tandem array on the chromosome were constructed and examined for their TcR level. A nearly proportional relationship between the TcR level and copy number of tetBS908 existed. PMID- 1900440 TI - Cell damage caused by ATP depletion is reduced by magnesium and nickel in human fibroblasts--a non-specific calcium antagonism? AB - Calcium has been suggested to be the final common mediator of cell damage, but conflicting reports to prove this hypothesis have appeared. In order to elucidate the role of calcium in cell damage caused by ATP depletion, the effect of addition of calcium channel blockers (verapamil and nitrendipine) and non specific antagonists (magnesium and nickel) was investigated in a model system of quiescent fibroblasts. ATP depletion was induced by metabolic inhibitors and the cell damage was assessed by the release of lactate dehydrogenase. Verapamil and nitrendipine did not protect the cells during ATP depletion, whereas a high concentration of Mg2+ (3-10 mmol/l) or a lower concentration of Ni2+ (0.5-1.0 mmol/l) reduced the cell damage considerably. An increased extracellular concentration of Ca2+ resulted in augmented cell damage. The effect of Mg2+ and Ni2+ was not due to an interference with the metabolic inhibitors or a reduction of the energy consumption. Both Ni2+ and Mg2+ were able to counteract the cell damage induced by entrance of Ca2+ after addition of the ionophore A23187. However, Mg2+ and Ni2+ were deleterious for the cells during ATP regeneration after an initial ATP decrease. These results indicate that a non-specific antagonism of Ca2+ may reduce cell damage, and, therefore, that Ca2+ may have an important role in cell damage, but also that a non-specific antagonism of Ca2+ during regeneration of ATP depleted cells is deleterious. PMID- 1900439 TI - Potentiation of DNA mediated gene transfer in NIH3T3 cells by activators of protein kinase C. AB - The mechanisms involved in the translocation of exogenously added genetic information through the cellular cytoplasm and into the nucleus are essentially unknown. Several trans-cytoplasmic translocation systems operate within cells to transport information received by the plasma membrane into the nucleus. Protein kinase C may be functionally involved in many of these translocation mechanisms. In order to explore the involvement of protein kinase C activation in the cytoplasmic translocation of DNA, NIH3T3 fibroblasts were transfected using the calcium-phosphate co-precipitation method with a plasmid containing the lacZ gene and treated with tetradecanoylphorbol 12,13-acetate (TPA) or 1,2 dioctanoylglycerol (DiC8). Addition of TPA or DiC8 immediately after glycerol shock resulted in a 5-7-fold increase in the number of cells expressing beta galactosidase as well as a concomitant increase in the total amount of beta galactosidase activity in the population during periods of transient and stable expression. TPA added at later times resulted in lesser increases in the efficiency of transfection. In contrast, TPA added at the time of addition of the calcium-phosphate precipitate inhibited transfection. In support of a role for protein kinase C activation in enhancing DNA transfection, the TPA analog 4 alpha phorbol 12,13-didecanoate, which does not activate protein kinase C, was ineffective at enhancing transfection. Furthermore, treatment of cells with the protein kinase C inhibitor sphingosine blocked the TPA-mediated increase in transient and stable expression. The results suggest that protein kinase C activation enhances transfection of exogenous DNA through an as yet unknown mechanism. PMID- 1900441 TI - Fluorescence response in chlortetracycline-loaded neutrophils measures release of Ca2+ from intracellular membrane enclosed storage sites. AB - Chlortetracycline complexes with di- and trivalent cations resulting in an enhancement of its fluorescence emission intensity. Rabbit peritoneal neutrophils loaded with chlortetracycline gave a fluorescence response, even in the absence of extracellular Ca2+ and Mg2+, by a decrease in fluorescence intensity. The shift in the fluorescence emission maximum to lower wavelengths after the response suggested the response to be due to Ca2+ and not Mg2+ flux. The response was elicited by three mechanisms--a receptor-mediated mechanism by the chemotactic peptide, an ionophore-mediated one by lasalocid, and a detergent mediated response by digitonin. These observations indicated that the response was due to transport of calcium across membranes in the intracellular compartments and may be physiologically significant. Whereas extracellular Ca2+ did not significantly affect the chemotactic peptide and lasalocid-mediated responses, Ca2+ inhibited the digitonin-mediated responses in a dose-dependent manner possibly due to extracellular Ca2+ flooding the cytosol through the digitonin-permeabilized plasma membrane and equilibrating the Ca2+ gradient across the intracellular membranes. The data collectively indicate that the fluorescence response is due to release of Ca2+ across intracellular membranes from a Ca2+ storage site into the cytosol. PMID- 1900442 TI - Altered G-protein expression and adenylate cyclase activity in platelets of non insulin-dependent diabetic (NIDDM) male subjects. AB - Adenylate cyclase activity and levels of guanine nucleotide regulatory proteins (G-proteins) were compared in platelets from normal and non-insulin-dependent diabetic (NIDDM) male subjects. Whilst no differences were noted in basal and NaF stimulated adenylate cyclase activities the degree of stimulation achieved by both forskolin and prostaglandin, E1 was lower by some 34 and 52% respectively, in platelet membranes from diabetic subjects compared with those from normal control subjects. Altered alpha 1-adrenoceptor-mediated inhibition of prostaglandin E1-stimulated adenylate cyclase activity was evident; it being some 34% lower in platelet membranes from diabetic subjects compared to controls. Analysis of G-protein alpha-subunits, using specific anti-peptide antisera, showed that platelets from all subjects exhibited the Gi-2 and Gi-3, but not the Gi-1 forms of the inhibitory G-protein 'Gi' and all expressed the 42 kDa species of alpha-subunit of the stimulatory G-protein Gs. Whilst platelets of diabetic subjects had levels of Gs which were comparable to those found in control subjects their levels of Gi-2 and Gi-3 were some 49 and 75%, respectively, of those found in platelets from control subjects. It is suggested that changes in adenylate cyclase functioning and G-protein expression may contribute to altered platelet functioning in non-insulin-dependent diabetic subjects. PMID- 1900443 TI - Fluvoxamine versus desipramine: comparative polysomnographic effects. AB - Electroencephalogram sleep measures over a 4-week period were obtained on 35 inpatients with major depression (unipolar) who received either fluvoxamine or desipramine in a randomized double-blind trial. Fluvoxamine showed immediate rapid eye movement (REM) sleep suppression and an alerting effect on sleep continuity measures. In contrast, desipramine administration was associated with REM suppression and sleep continuity improvement. The "alerting" quality of fluvoxamine, similar to other serotonergic antidepressants, appears to be unrelated to a lack of clinical efficacy, but may be related to persistent REM sleep suppression. However, it is premature to comment on the serotonin specificity for REM sleep. PMID- 1900444 TI - The role of glycosylation in the biosynthesis and acquisition of ligand-binding activity of the folate-binding protein in cultured KB cells. AB - The biosynthesis, processing, and ligand-binding function of the membrane associated and soluble forms of the folate-binding protein (FBP) in KB cells, a cultured human cell line, were studied using pulse-chase labeling with [35S] methionine. The intermediary and mature forms of the protein were isolated by immunoprecipitation and affinity chromatography and analyzed by sodium dodecyl sulfate electrophoresis and autoradiography. The earliest species identified had an Mr of 32 Kd and disappeared over 5 hours concomitant with the appearance of a 38-Kd cellular FBP. As the 38-Kd species disappeared, a 40-Kd form appeared in the medium. When tunicamycin was added to the culture medium to inhibit core glycosylation, a 26-Kd aglycosylated species and minor 28-Kd and 30-Kd forms appeared. Endoglycosidase H, which cleaves high mannose but not complex oligosaccharides, reduced the 32-Kd species to 26-Kd but the enzyme had no effect on the 38-Kd form, indicating that this species is complex glycosylated. Monensin, which blocks complex glycosylation, also inhibited synthesis of the 38 Kd species. Although both the 32-Kd and 38-Kd forms had ligand-binding sites (as demonstrated by binding to a folate-Sepharose matrix), the 26-Kd aglycosylated species, labeled in the presence of tunicamycin, lacked similar binding sites because it did not bind to the affinity matrix. In contrast, the aglycosylated 26 Kd form, which was obtained by treatment of the 32-Kd species with endoglycosidase H, did bind to the folate affinity matrix, indicating that it retained ligand-binding function. Thus, the high mannose oligosaccharide moiety is not required for the folate-binding property of the FBP, but its addition to the polypeptide chain precedes a later step that is necessary for the mature protein to have ligand-binding function. PMID- 1900445 TI - Homeostatic action of interleukin-4 on endogenous and recombinant interleukin-2 induced activated killer cell function. AB - Cytokine-secreting, major histocompatibility complex-unrestricted activated killer (AK) cells are toxic to a wide range of virus-infected or malignant target cells and may be generated endogenously, eg, after bone marrow transplantation, or by infusion of cytokines such as recombinant interleukin-2 (rIL-2). Although AK cells secrete cytokines such as gamma-interferon and tumor necrosis factor, which are themselves able to recruit fresh cytokine-secreting AK cells, activation in both settings is short-lived, implying the existence of homeostatic regulatory mechanisms. We now demonstrate one mechanism by which rapid homeostasis is achieved. We show that IL-4 is produced in patients with both endogenously and exogenously generated AK cells. The cytokine was detected in serum after marrow transplantation, and IL-4 transcripts appeared in circulating lymphocytes during rIL-2 infusion. Although IL-4 inhibited the induction phase of AK cell function, it had no significant inhibitory effect on the ability of AK cells from these individuals to respond to restimulation. Nonetheless, neutralization of the IL-4 induced during cell activation doubled the half-life of AK function, once activating stimuli were removed, from 18 to 44 hours and produced a 2-log increase in AK cell secretion of tumor necrosis factor and gamma interferon. These data suggest that IL-4 induced in vivo during lymphocyte activation abbreviates AK cell responses once the triggering stimuli have been removed. Neutralization of endogenous IL-4 in vivo by appropriate monoclonal antibodies might prolong the duration of AK function. PMID- 1900446 TI - Generation of nitric oxide from organic nitrovasodilators during passage through the coronary vascular bed and its role in coronary vasodilation and nitrate tolerance. AB - This study investigated the release of nitric oxide (NO) from glyceryl trinitrate (GTN) and SIN-1 in Langendorff rabbit hearts. Infusion of either GTN (10-40 microM) or SIN-1 (0.45-4.5 microM) into the coronary inflow tract resulted in a decrease in coronary perfusion pressure and NO release (oxyhemoglobin technique) into the coronary effluent. NO release from SIN-1 occurred spontaneously whereas passage through the coronary circulation, i.e. active metabolism, was required for NO release from GTN. Removal of the coronary endothelium and blockade of endothelial NO formation did not affect NO release from GTN and SIN-1. In GTN tolerant hearts, there was a considerable inhibition of GTN- but not SIN-1 induced NO formation and coronary vasodilation. These data suggest (1) that metabolic NO release from GTN occurs during passage of the coronary circulation and is independent of the presence of endothelium, and (2) reduced NO release is a major cause of nitrate tolerance. PMID- 1900447 TI - Endothelium-dependent contractions. AB - The endothelial cells help to control the tone of the underlying vascular smooth muscle by releasing vasoactive factors. In physiological circumstances, the release of relaxing factors (nitric oxide and endothelium-derived hyperpolarizing factor) appears to predominate. However, in certain blood vessels (peripheral veins and large cerebral arteries), the normal endothelium has the propensity to release vasoconstrictor substances, among which are superoxide anion and thromboxane A2; the release of these endothelium-derived vasoconstrictors may contribute to the autoregulatory processes. In most blood vessels, anoxic conditions initiate the release of an unidentified endothelium-dependent contracting factor. Cultured endothelial cells, and blood vessels maintained under culture conditions for prolonged periods of time, release the vasoconstrictor peptide endothelin. A characteristic of vascular diseases is that the ability of the endothelial cells to release relaxing factor(s) is reduced, while the generation of contracting factor is maintained or enhanced. PMID- 1900448 TI - Increase of DT-diaphorase activity and atrophy of thymus by organotin compounds. PMID- 1900449 TI - Effects of simulated field spraying of carbofuran, carbaryl and dimethoate on pheasant and partridge chicks. PMID- 1900450 TI - Effects of benzo(a)pyrene on food assimilation and growth efficiency in Porcellio scaber (Isopoda). PMID- 1900451 TI - Cadmium toxicity to photosynthesis and associated electron transport system of Nostoc linckia. PMID- 1900452 TI - Distribution of sensitivity to 4-nitroquinoline 1-oxide among Japanese lymphoblastoid cell lines. PMID- 1900454 TI - Solid and cystic pancreatic tumors. Clinical, histochemical, and electron microscopic features in ten cases. AB - Ten cases of the rare solid and cystic pancreatic tumors are presented. All except one occurred in young women (mean age, 25 +/- 9.2 years). The large neoplasms were evenly distributed across the pancreas; in one case, metastasis occurred; all other cases were free from disease after complete resection. Histologic hallmarks of solid and cystic neoplasms were papillary growth, large intracytoplasmic granules, and immunoreactivity with alpha 1-antitrypsin, alpha 1 antichymotrypsin, phospholipase A2, and neuroendocrine markers (neuron-specific enolase [NSE], synaptophysin). This suggests both endocrine as well as exocrine differentiation. PMID- 1900453 TI - Acute myeloblastic leukaemia--a model for assessing value for money for new treatment programmes. AB - OBJECTIVE: To measure the effects of changes in treatment of acute myeloblastic leukaemia that may give better value for money. DESIGN: Retrospective analysis of patients' notes to identify items of management costing money; prospective costing of these items. The Medical Research Council acute myeloblastic leukaemia 9 trial was used to identify the amount and distribution of these costs when either one or two courses of induction treatment were required to obtain complete remission. These findings were then extrapolated to four published international controlled trials using similarly intense treatment and in which the number of courses of treatment required for complete remission was stated, to compare British costs for treatment with idarubicin and daunorubicin, both in combination with cytarabine. SETTING: Leukaemia unit, Royal Marsden Hospital, London. SUBJECTS: Data on 10 patients receiving intensive induction treatment for acute myeloblastic leukaemia were used to identify 160 items of cost in four broad groups: general (including accommodation), diagnostic, supportive treatment, and cytotoxic chemotherapy. One newly treated patient was prospectively assessed over one month, including a time and motion study, to cost these items; then costs for 268 patients from the MRC trial receiving moderate induction chemotherapy including daunorubicin were assessed, and costs for treatment of 522 patients in the four international studies comparing daunorubicin with idarubicin were analysed. MAIN OUTCOME MEASURES: Cost effectiveness was measured as the overall cost to obtain complete remission in untreated patients with acute myeloblastic leukaemia after treatment with idarubicin or daunorubicin. RESULTS: The 160 costed items were measured for their sensitivity in varying the total cost of treatment, this being assessed within Britain in other district general and private hospitals to measure the extremes of cost of these items. Overall, idarubicin, although more expensive, showed a substantial saving (1477 pounds per patient) in total hospital costs, more than offsetting the increased cost (607 pounds) of the new treatment, an overall savings of 870 pounds per patient (5%). CONCLUSION: Approaches modelling cost effectiveness may be an essential part of planning new programmes of treatment in the future. This method can be used to estimate the cost effectiveness of the treatments in different environments and countries where costs may vary widely. PMID- 1900455 TI - Barnase toxin: a new chimeric toxin composed of pseudomonas exotoxin A and barnase. AB - We have constructed a chimeric toxin composed of Pseudomonas exotoxin A (PE) and the extracellular ribonuclease of Bacillus amyloliquefaciens, barnase. The chimeric protein, termed PE-Bar, reacted with both anti-PE and anti-barnase antisera and had both ADP ribosylation and ribonuclease activities. The chimeric toxin was cytotoxic to the murine fibroblast cell line L929 and to a murine hybridoma resistant to PE. A mutant form of PE-Bar lacking ADP-ribosylating activity was still cytotoxic to L929 cells. Because treatment of cells prelabeld with [3H]uridine resulted in a decrease in their RNA content, we conclude that this cytotoxic effect was due to the ribonuclease activity of barnase molecules that had been translocated to the cytosol. It is now possible to construct chimeric toxins with two or more enzymatic activities that can be delivered to the cytosol of the target cells. PMID- 1900456 TI - Cellular immunity to HIV activated by CD4 fused to T cell or Fc receptor polypeptides. AB - We describe functional simplified T cell and Fc receptor chimeras that are capable of directing CD8+ cytotoxic T lymphocytes (CTLs) to specifically recognize and lyse cells expressing HIV envelope proteins. Target cells bearing HLA-DR molecules are not recognized by CTL armed with the chimeras. The variety of cell types in which the native receptors are active suggests multiple possibilities for antiviral intervention through genetic means. PMID- 1900457 TI - rab5 controls early endosome fusion in vitro. AB - The small GTP-binding protein rab5 was previously localized on early endosomes and on the cytoplasmic face of the plasma membrane. Using a cell-free assay, we have now tested whether rab5 is involved in controlling an early endocytic fusion event. Fusion could be inhibited by cytosol containing the overexpressed mutant rab5lle133, which does not bind GTP on blots, and by antibodies against rab5, but not against rab2 or rab7. In contrast, fusion was stimulated with cytosol containing overexpressed wild-type rab5. Cytosols containing high levels of rab2 or mutant rab5 with the 9 carboxy-terminal amino acids deleted, which bind GTP on blots, had no effects. Finally, the inhibition mediated by anti-rab5 antibodies could be overcome by complementing the assay with the cytosol containing wild type rab5, but not with the same cytosol depleted of rab5, nor with cytosol containing the rab5 mutants or rab2. These in vitro findings strongly suggest that rab5 is involved in the process of early endosome fusion. PMID- 1900458 TI - IP-1: a dominant inhibitor of Fos/Jun whose activity is modulated by phosphorylation. AB - Transcription factor AP-1 is inducible by phorbol esters and thus could be considered to be one final target of the protein kinase C signal transduction pathway. AP-1 consists of the products of the fos and jun oncogenes, which associate as dimers to bind TPA-responsive promoter elements (TRE) efficiently. We show that AP-1 activity is modulated by an inhibitory protein (IP-1), present both in the nucleus and cytoplasm of several cell types. IP-1 specifically blocks DNA binding of AP-1 from nuclear extracts and of in vitro synthesized Fos/Jun proteins. It is a labile protein of 30-40 kd, which exerts its activity only in the nonphosphorylated form. Block of IP-1 function is obtained by PKA-mediated phosphorylation, possibly suggesting a cross talk mechanism at transcriptional level. Competition experiments with synthetic peptides suggest that IP-1 could interact with Fos and/or Jun leucine zippers. We speculate that IP-1 might act as a transcriptional antioncogene. PMID- 1900459 TI - Somatic generation of diversity in a mammalian primary lymphoid organ: the sheep ileal Peyer's patches. AB - Ileal Peyer's patches (IPPs) in the sheep are composed of tightly packed follicles in which surface IgM-positive B cells proliferate and can be exported to the periphery. We report that the light chain rearrangement pattern in a single IPP follicle is much more restricted than in the entire tissue, which indicates that, as in the chicken bursa, ongoing rearrangement does not take place in this organ. Moreover, we show that B cells extensively diversify their antigen receptor while proliferating in IPP follicles. Sequencing of part of the V lambda locus indicates that this diversification is not achieved by gene conversion, but rather by untemplated somatic mutation and intense selective pressure. These results strongly imply that sheep IPPs behave as a bursa equivalent, primary lymphoid organ of diversification and that somatic point hypermutation, which is known to proceed during secondary immune responses, can also generate an antibody repertoire. PMID- 1900460 TI - First isolates of norfloxacin-resistant penicillinase-producing Neisseria gonorrhoeae (PPNG) in Canada. PMID- 1900461 TI - Lymphokines and immunoregulatory molecules in subacute sclerosing panencephalitis. AB - Frozen brain specimens from six patients with subacute sclerosing panencephalitis (SSPE) were analyzed immunohistochemically for the presence of leukocyte subpopulations and specific cytokines. In brain regions demonstrating perivascular cell infiltration and gliosis, CD4 and CD8 positive cells were identified within the brain parenchyma. Cytokine analysis revealed cells staining positively for tumor necrosis factor-alpha and interferon-gamma. These results were similar to those observed in multiple sclerosis (MS) and progressive rubella panencephalitis tissue and were different from other predominantly noninflammatory neurologic diseases and normal controls. Although SSPE and MS differ significantly in their etiology and histopathology, the similarities in leukocyte and cytokine staining patterns suggest a common mechanism of disease progression. PMID- 1900462 TI - Hepatocyte growth inhibitory factor derived from HTLV-I(+) T cell lines: effect on the epidermal growth factor-dependent proliferation of rat hepatocytes. AB - A human T cell leukemia virus-I infected T cell line, ATL-2, produces an interleukin-2 receptor inducing factor, adult T cell leukemia (ATL)-derived factor (ADF). In the conditioned medium (CM) of ATL-2, we found an inhibitory activity on the epidermal growth factor (EGF)-dependent proliferation of primary cultured rat hepatocytes, measured by cell number and [3H]thymidine incorporation. ATL-2 CM dose-dependently inhibited hepatocyte proliferation. This activity was fractionated by gel filtration at a molecular size of 15,000 to 40,000 and was tentatively called hepatocyte growth inhibitory factor (HGI). Further fractionation with the ion-exchange column indicated that HGI was separable from ADF. Nevertheless, there was a positive correlation between HGI and ADF production, because the HGI activity was also detected in the CM of another ADF producer cell line (HUT102), while no significant HGI activity was detected in the CM of low ADF producer cell lines, ED and MOLT4. PMID- 1900464 TI - [The diagnosis of neurofibromatosis]. PMID- 1900465 TI - ["Lupus anticoagulans" in immune hyperthyroidism]. PMID- 1900463 TI - Absence of modulation of monokine production via endogenous cyclooxygenase or 5 lipoxygenase metabolites: MK-886 (3-[1-(4-chlorobenzyl)-3-t-butyl-thio-5 isopropylindol-2-yl]-2,2- dimethylpropanoic acid), indomethacin, or arachidonate fail to alter immunoreactive interleukin-1 beta, or TNF-alpha production by human monocytes in vitro. AB - Human peripheral blood monocytes exposed to MK-886 (3-[1-(4-chlorobenzyl)-3-t butyl-thio-5-isopropylindol-2-yl]-2,2- dimethylpropanoic acid) at doses which abolish formation of 5-lipoxygenase metabolites showed unaltered interleukin-1 beta (IL-1 beta) or tumor necrosis factor-alpha (TNF-alpha) levels in response to phorbol ester, concanavalin A, serum-treated zymosan, or lipopolysaccharide. Indomethacin (10 microM), alone or in combination with MK-886, also failed to modulate monokine production in response to any stimulus. Exogenous arachidonate (3-30 microM) which augmented the formation of PGE2 and LTB4 in the absence of stimulation, also had no effect on monokine production. LPS-induced IL-1 and TNF production occurred despite stimulation of PGE2 synthesis. The results make a role for endogenous prostaglandins and leukotrienes in the regulation of monocyte IL-1 beta and TNF-alpha production unlikely. These data also indicate that MK 886, a novel inhibitor of 5-lipoxygenase product formation, is a potentially useful leukotriene inhibitor which does not affect monokine production. PMID- 1900466 TI - [Clinical significance of the fibrinolysis system]. PMID- 1900468 TI - Community-wide outbreak of Neisseria gonorrhoeae conjunctivitis in Konso district, North Omo administrative region. AB - We describe a large outbreak of severe pustular conjunctivitis due to Neiserria gonorrhoeae. Over 9,000 cases occurred during 8 months in 1987-1988 in one district in North Omo, Ethiopia. Both sexes and all age groups were affected, particularly children under 5 years of age; only a small minority were neonates. Despite a highly successful cure rate for individual cases, the outbreak continued for a number of months. Several epidemiologic approaches were used to monitor the outbreak and identify the mechanism of transmission. The epidemic curve suggested person-to-person transmission. Routine surveillance data showed that there was no concurrent genital gonorrhea outbreak and genital transmission could not explain a community-wide outbreak. In the setting of intense crowding and relative lack of water, peak transmission of illness coincided with two periods following the rains, suggesting that flies were important in transmission. A case-control study identified lack of face-washing as a household risk factor. Eighty seven of one-hundred and forty six (59%) control houses with children were judged to contain children with clean faces, while only 102 of 216 (47%) case households contained children with clean faces (p less than .05). Our recommendations include measures to improve personal hygiene. PMID- 1900467 TI - An acetylcholine receptor alpha-subunit promoter conferring preferential synaptic expression in muscle of transgenic mice. AB - We have obtained transgenic mice expressing nuclearly targeted beta-galactosidase (nls-beta-gal) under the control of a chicken acetylcholine receptor alpha subunit promoter. The expression of the transgene was detected in early somites, starting before embryonic day 9.5. In 13-day embryos, the expression pattern of the transgene closely paralleled that of the endogenous mouse alpha-subunit gene, assessed by in situ hybridization. Our results illustrate, with single-cell resolution, the tissue specificity of this alpha-subunit promoter during embryogenesis. After birth, the overall beta-galactosidase activity rapidly decreased with age. However, in diaphragms of newborn animals, beta-galactosidase activity selectively persisted in nuclei underlying the motor endplates. The latter were revealed by an acetylcholinesterase stain. Nls-beta-gal was also visualized by indirect immunofluorescence, while endplates were labelled with fluorescent alpha-bungarotoxin. Confocal microscopy unambiguously identified the more intensely stained nuclei as synaptic 'fundamental nuclei', and allowed estimates of relative staining levels. Thus an 842 bp acetylcholine receptor gene promoter confers preferential synaptic expression to a reporter gene within myofibres in vivo. PMID- 1900469 TI - The management of diabetic ketoacidosis by continuous infusion of low-dose insulin using the ordinary intravenous plastic bag and tubing. AB - Although the hourly intramuscular insulin regimen has been used in the management of diabetic ketoacidosis (DKA) in Ethiopia for over 7 years, continuous intravenous (IV) insulin infusion has never been previously used. In Tikur Anbessa Hospital, Addis Abeba, in 198788, we used the ordinary IV plastic bag and tubings alone to concurrently infuse the low-dose insulin and hydration solution in the management of 15 episodes of DKA in 13 patients, 5 males and 8 females. Initial blood glucose was over 400 mg/dl and urine ketones 4+ in all, and the level of consciousness ranged from drowsy to coma. Initially, 5 to 10 units of crystalline zinc insulin (CZI) was given IV directly to all but 2 patients. Then CZI was added to the normal saline IV bag and the dose of insulin was adjusted according to fluid requirements while at the same time maintaining the insulin rate at 5 to 10 units/hour until the blood glucose dropped to 250 mg/dl or lower. At this point the IV fluid was changed to 5% dextrose and the insulin infusion was reduced to 2 to 4 units/hour. The mean insulin requirement until the dextrose infusion was initiated was 33.2 +/- 7.3 units, IV fluid requirement was 3.5 +/- 0.8 litres and mean duration of treatment 4.4 +/- 1.6 hours. There was one death which was not due to insulin resistance, while all other patients fully recovered. The study demonstrates that insulin infusion using the ordinary IV plastic bag and tubings is safe, simple, and convenient in the management of DKA and hence should be used whenever indicated and feasible. PMID- 1900470 TI - Effect of phenylephrine on pyruvate dehydrogenase in fasting rat livers. AB - Previous estimates of flux through the pyruvate-dehydrogenase complex were made by measuring 14CO2 generated from oxidation of [1-14C]pyruvate, assuming a 1:1 stoichiometry. However, this method fails to discriminate between 14CO2 produced from pyruvate dehydrogenase and 14CO2 generated from phospho-enolpyruvate carboxykinase and citric-acid-cycle dehydrogenases. While some previous reports have attempted to correct for the additional 14CO2 production by comparing 14CO2 generated by [1-14C]pyruvate with [2-14C]pyruvate or [3-14C]pyruvate, the estimates are flawed by failure to determine the radioactivity and distribution of the 14C label in the oxalacetate pool. The present method circumvents these problems by utilizing [1,4-14C]succinate to radiolabel the oxalacetate pool and by directly measuring the specific radioactivity of malate. The results demonstrate that flux through the pyruvate-dehydrogenase complex is negligible compared to the other reactions which generate 14CO2 from [1-14C]lactate in the fasted state. Phenylephrine did not significantly alter this result in the fasted state. However, 14CO2 production via the pyruvate-dehydrogenase complex is large (approximately 11.5 nmol.min-1.mg mitochondrial protein-1) compared to 14CO2 production via phosphoenolpyruvate carboxykinase and citric-acid-cycle dehydrogenases (approximately 6.4 nmol.min-1.mg-1) when the pyruvate dehydrogenase complex is activated, in the fed state with 1 mM dichloroacetate. PMID- 1900471 TI - An Ig-A-like substance in the chicken's pineal. AB - Immunohistochemistry revealed an Ig-A-like substance on the luminal surface of the pineal follicles and in the parafollicular layer. This substance was observed around 1 week of age and disappeared by 8 weeks at the time when the transformation of the follicular pattern leads to an adult-type pineal tissue. PMID- 1900472 TI - B-Z transition of poly(dG-m5dC) induced by binding of Lys-containing peptides. AB - Effects of oligopeptides containing Lys residues on the conformation of poly(dG m5dC) have been investigated by circular dichroism spectroscopy. Lys-Ala-Lys (KAK) and its longer analogs with Lys-Ala repeats are found to convert the B-form polynucleotide to the Z form very efficiently. The ability to induce the B-Z transition is characteristic of alternating Lys-Ala sequences and increases exponentially with increasing number of the repeats. The heptapeptide KAKAKAK has an ability comparable with that of spermine, one of the most effective inducers hitherto known. The present results provide the first example of the B-Z transition of poly(dG-m5dC) induced by peptide binding. PMID- 1900473 TI - Modulation of a Shaker potassium A-channel by protein kinase C activation. AB - Brain fast transient K+ channel (A channel) is known to be modulated by PKC activation. We studied, by two-electrode voltage clamp, the molecular mechanism of modulation by PKC activation of A-channels expressed in Xenopus oocytes from the Shaker H4 clone. The modulation is inhibitory affecting primarily the maximal conductance of the channels. A secondary effect is a small change in the voltage dependence of activation and inactivation of the channel. PMID- 1900474 TI - Protein kinase C subspecies in adult rat hippocampal synaptosomes. Activation by diacylglycerol and arachidonic acid. AB - Synaptosomes isolated from the adult rat hippocampus contain the alpha- and beta subspecies of protein kinase C (PKC), but not the gamma-subspecies which is abundantly expressed in the pyramidal cells in this brain region. Although the gamma-subspecies is known to respond significantly to free arachidonic acid, it is found that both the alpha- and beta-subspecies are also activated dramatically by arachidonic acid in synergistic action with diacylglycerol. Oleic, linoleic, and linolenic acids are all active. It is possible that unsaturated fatty acids may take part in the activation of alpha- and beta-subspecies of PKC which are present in the presynaptic nerve endings terminating at the hippocampal pyramidal cells. PMID- 1900475 TI - Activation of protein kinase C inhibits hormonal stimulation of the GTPase activity of Gi in human platelets. AB - The effect of 12-tetradecanoyl phorbol 13-acetate on the GTPase activity of Gi was investigated. Treatment with TPA did not alter basal GTPase activity of membranes or the stimulatory effect of prostaglandin E1 (putatively via Gs). In contrast, the phorbol ester markedly diminished stimulation of GTPase by agents whose receptors are coupled to Gi such as epinephrine (alpha-adrenergic action), platelet activating factor or thrombin. Pertussis toxin catalyzed ADP ribosylation was also decreased in membranes from TPA-treated platelets as compared to the controls. It is suggested that the alteration in the hormonal activation of the GTPase activity of Gi is secondary to a perturbation in the receptor-Gi interaction. PMID- 1900476 TI - The role of superovulation with menotropins in ovulatory infertility: a review. AB - The risks of menotropin therapy (ovarian hyperstimulation syndrome, multiple gestation, adnexal torsion) are well known and have been previously described. Superovulation should not be considered for the indications described herein until more traditional therapies for infertility have been tried and found unsuccessful and sufficient time has elapsed for conception to occur. The cost of superovulation is high: the medications are expensive, frequent E2 monitoring and US studies are costly, and pregnancy complications relating to the higher rate of pregnancy loss and multiple gestation may add substantially to the overall cost. Yet, compared with IVF and GIFT, superovulation cycles combined with IUI cost between one third to one sixth that of an IVF cycle. Protocols involving combined CC/hMG/hCG, which reduce the total number of ampules of Pergonal needed per cycle and still provide multiple follicular development, may further reduce costs. There is a growing consensus that superovulation-IUI protocols should be attempted before GIFT and IVF in couples with normal pelvic viscera. There is little doubt that IVF and GIFT cycles are more costly, stressful, and complex. No comparative data have clearly shown IVF and GIFT to be superior to superovulation protocols in ovulatory women with normal pelvic anatomy. In the only study examining this issue published to date, Kaplan et al. retrospectively analyzed all GIFT and superovulation/IUI cycles at a single university center and found GIFT to be three times more efficient. However, the inherent limitations of a nonrandomized, nonprospective study of this kind are obvious as these authors have suggested. Therefore, it may be wise to consider the use of superovulation before assisted reproductive technologies until this issue is settled. It would be interesting to determine if the high PRs reported for couples with unexplained infertility or mild endometriosis in IVF and GIFT cycles in some centers not incorporating superovulation/IUI protocols would hold up if such an approach was routinely followed. Despite the increasing acceptance of superovulation protocols, we must be aware that many of the studies suggesting a role of hMG in treating ovulatory infertile women with normal pelvic anatomy suffer from deficiencies in experimental design. In a payor-driven system, such as in the United States, the difficulties in designing and carrying out scientifically sound clinical studies examining infertility therapies are obvious. The lack of federal or outside funding for the study of infertility issues contributes to the problem. It is our hope that better designed studies examining the role of superovulation in the treatment of ovulatory infertile women with normal pelvic anatomy will be forthcoming. PMID- 1900477 TI - Gonadotropin treatment for the ovulatory patient--the pros and cons of empiric therapy for infertility. PMID- 1900478 TI - The role of endogenous opiates in athletic amenorrhea. AB - We hypothesized that menstrual disturbances in female athletes arise from opioid induced abnormalities in gonadotropin and/or prolactin (PRL) secretion. To investigate this hypothesis, we measured luteinizing hormone, follicle stimulating hormone, and PRL levels in eumenorrheic and amenorrheic athletes during thyrotropin-releasing hormone and gonadotropin-releasing hormone tests at baseline, after naloxone infusions, after exercise to exhaustion, and after similar exercise during naloxone infusions. Contrary to our hypothesis, amenorrheic runners did not have significant alterations in basal, postexercise, or stimulated hormone levels compared with eumenorrheic runners. In addition, opioid blockade by naloxone did not enhance gonadotropin release by amenorrheic athletes. PMID- 1900479 TI - Short-term modulation of gonadotropin secretion by progesterone during the luteal phase. AB - Progesterone (P) levels were acutely augmented by intravenous (IV) infusion in seven women in the midluteal phase to ascertain if short-term changes in P levels have an effect on gonadotropin secretion. During four 6-hour intervals of alternating control and IV P infusion, each subject underwent blood sampling for luteinizing hormone (LH), follicle-stimulating hormone (FSH), and P every 20 minutes for 24 hours. As a result of the P infusions, mean (+/- SE) P levels rose 72% from a control level of 26.24 +/- 2.13 to 45.22 +/- 3.47 nmol/L, whereas mean LH levels were reduced by 20% from a control level of 4.82 +/- 0.67 to 3.85 +/- 0.66 IU/L. During P infusions, mean LH pulse amplitude was reduced by 33% from 3.33 +/- 0.37 to 2.23 +/- 0.28 IU/L. The mean LH interpulse interval increased by 93% (2.56 +/- 0.14 to 4.92 +/- 0.15/h) when the interval between pulses was interdicted by the onset of P infusion. The infusion of P reduced mean FSH levels by 10% from 3.34 +/- 0.41 to 3.01 +/- 0.35 IU/L. These findings suggest that acute elevations in P levels within the physiological range have a short-term inhibitory effect on gonadotropin secretion during the midluteal phase. PMID- 1900480 TI - A multiparametric analysis of endometrial estrogen and progesterone receptors after the postovulatory administration of mifepristone. AB - A double-blind randomized study was performed in two groups of eight normally cycling patients: group I received 10 mg/d of RU486 for 4 days from the date of ovulation and group II received a placebo. On day +5, cytosol and endometrial estrogen receptors (ERs), and progesterone receptors (PRs) were analyzed by radioligand binding assay as well as by enzyme immunochemistry. Histologic studies showed that all the endometria of group I were abnormal (luteal insufficiency and/or E/P imbalance). The nuclear PR levels were significantly higher in group I (843 +/- 422 fmol/mg) deoxyribonucleic (DNA) compared with 482 +/- 232 fmol/mg DNA in group II. Immunohistochemical study showed that ER and PR staining was higher for both glands and stroma in group I (52% and 72% for the respective receptors), compared with the receptor-immunostained surface observed in group II, which was reduced to 40% for ER and to 4% for PR. This study demonstrates that RU486 administered in the immediate postovulatory period blocks normal tissue evolution in the follicular phase as well as the processing of PR. PMID- 1900481 TI - Lower pregnancy rate with premature luteinization during pituitary suppression with leuprolide acetate. AB - The relationship of the circulating level of progesterone (P) on the day of human chorionic gonadotropin (hCG) injection to occurrence of clinical pregnancy was examined in 133 leuprolide acetate human menopausal gonadotropin (hMG) in vitro fertilization cycles in women having at least three embryos transferred. Progesterone concentrations greater than 0.5 ng/mL were associated with a significantly lower rate of pregnancy (12/59, 20%) compared with less than 0.5 ng/mL (40/74, 54%, P less than 0.005). The higher P cycles were associated with greater patient age and hMG dose, although these relationships appeared to be indirect. Luteinizing hormone (LH) concentrations remained suppressed. Ovarian stimulation may cause excessive luteinization and an adverse cycle outcome even in the presence of low LH levels. Prospective use of P levels may be helpful to determine optimal hCG timing. PMID- 1900482 TI - Follicular monitoring and outcome of in vitro fertilization in gonadotropin releasing hormone-agonist-treated cycles. AB - Previous investigations of in vitro fertilization (IVF) cycles stimulated with gonadotropins have shown that it is possible to predict IVF outcome on the basis of the pattern of estradiol (E2) production in the terminal phase of follicular growth. This analysis looked at endocrine and ultrasound parameters in the late follicular phase of 320 patients in their first cycle of IVF. All cycles were stimulated by an association of gonadotropin-releasing hormone agonists (GnRH-a) and human menopausal gonadotropins (hMG). The pregnancy rate (PR) was not related to the E2 pattern in the 5 days before ovulation induction and was 33% and 39% even when E2 values fell during hMG administration. The PR was independent of the E2 level and the number of follicles greater than 14 mm on the day of human chorionic gonadotropin administration (day 0). The incidence of multiple pregnancy increased when E2 levels were greater than 1,000 pg/mL. It is concluded that follicular phase parameters used for cycle cancellation in hMG-stimulated IVF cycles cannot be extrapolated to GnRH-a/hMG cycles. PMID- 1900483 TI - Gonadotropins and combined gonadotropin-releasing hormone agonist--gonadotropins protocols in a randomized prospective study. AB - A prospective study was designed to compare cycles stimulated by human menopausal gonadotropin (hMG) (group A) with cycles pretreated with gonadotropin-releasing hormone agonist causing pituitary desensitization followed by hMG stimulation (group B). Three hundred two cycles were randomly allocated to each group. Cancellation rate was 27.2% in group A compared with only 3.3% in group B. Significantly less hMG ampules for a shorter period were needed in group A patients. Lower estradiol and higher luteinizing hormone levels were detected in the hMG group. Patients in group B yielded significantly more oocytes and more embryos per retrieval. A significantly higher pregnancy rate per cycle was obtained in group B (27%) as compared with that of group A (13%). Moderate and severe ovarian hyperstimulation syndrome was significantly more frequent in group B than in group A. PMID- 1900484 TI - Correlation of endometrial histology, morphometry, and ultrasound appearance after different stimulation protocols for in vitro fertilization. AB - The role of endometrial factors in controlling embryo implantation is poorly understood. In the present study, histopathology and morphometry were used to investigate differences in endometrial appearance seen by ultrasound (US) in 107 in vitro fertilization patients receiving different superovulation regimens. Seventy-seven patients received clomiphene citrate (CC)/human menopausal gonadotropin (hMG) and 30 buserelin acetate down regulation/hMG. All patients received an endometrial US at the time of embryo transfer (ET). Endometrial biopsies were taken from 17 women (12 CC/hMG, 5 buserelin acetate/hMG) with fertilization failure at the time when ET would normally have occurred. The morphometry results showed that endometrial glandular volume 2 days after oocyte retrieval was significantly reduced after CC/hMG compared with buserelin acetate/hMG, despite the fact that histopathological dating was similar for both groups. In addition, significant differences in endometrial thickness and echogenicity between CC/hMG and buserelin acetate/hMG were evident by US. PMID- 1900485 TI - Placebo-controlled trial of high-dose Mesterolone treatment of idiopathic male infertility. AB - The possible effect of Mesterolone (Schering N.V., Brussels, Belgium) (1 alpha methyl-5-alpha-androstane-17 beta-ol-3-one) on semen quality and fertility of men with idiopathic oligoasthenospermia and/or teratozoospermia has been evaluated in a double-blind trial. The study included 52 patients who were treated during 12 months with either 150 mg/d of Mesterolone or placebo. The overall pregnancy rate was similar in the Mesterolone-treated cases (26%) and in the placebo control cases (48%), although a significant increase in motility and in the proportion of spermatozoa with normal morphology was recorded in the Mesterolone-treated cases. Because similar semen improvement also occurred in the placebo controls, our findings cast doubt on the possible usefulness of high-dose Mesterolone treatment of idiopathic male infertility. PMID- 1900486 TI - Luteinizing hormone pulse frequency and in vitro bioactivity in male idiopathic infertility. AB - We investigated 51 patients with idiopathic oligospermia and 10 control subjects. Blood samples were collected every 20 minutes from 10 P.M. to 10 A.M. and luteinizing hormone (LH) pulsatility was analyzed. A pool of all samples obtained from each subject was used to measure bioactive LH in an in vitro mouse Leydig cell bioassay and immunoactive LH in an immunoradiometric assay. Mean immunoactive LH pulse frequency was higher and mean bioactive to immunoactive LH ratio was lower in infertile men than in controls. There was a significant negative correlation between bioactive LH to immunoreactive LH ratio and LH pulse frequency. These data indicate that the defect in the gonadal axis in oligospermic men resides not in the hypothalamic-pituitary function but rather in the testis itself. PMID- 1900487 TI - Hypergonadotropinemia not associated to ovarian failure and induced by factors interfering in radioimmunoassay. AB - Unexpectedly high LH and FSH serum levels, measured by conventional RIA methods employing a rabbit antibody, were observed in eight women 18 to 34 years of age who came to our observation for acne and/or hirsutism and with no sign of premature ovarian failure. Reinvestigation of patient histories revealed that all of them had previously received multiple injections of a multimicrobial vaccine containing rabbit proteins. Luteinizing hormone and FSH were remeasured by IRMA and ELISA. These techniques revealed that serum levels of both gonadotropins were within the normal range in all subjects. We believe that falsely elevated gonadotropin levels were induced by the presence of heterophilic antibodies against rabbit serum interfering in the conventional RIA. PMID- 1900488 TI - Effect of estrogen/progestin administration on the ovarian response to gonadotropins: a randomized, prospective study. AB - The findings of our study indicate that women pretreated with E/progestin demonstrate increased gonadotropin requirements when undergoing ovulation induction. Whether this treatment has a significant effect on the outcome of ovulation induction in patients receiving gonadotropins remains to be established. PMID- 1900489 TI - A pilot study of the use of gonadotropin-releasing hormone analog for triggering ovulation. AB - Our study demonstrated the feasibility of using GnRH-a for triggering ovulation in women receiving hMG for ovulation induction: 11 of 13 patients had good pituitary LH and FSH surge followed by normal ovulatory P rise, and 4 became pregnant. In a selected group of patients, this method for triggering ovulation may be advantageous to using hCG. PMID- 1900490 TI - Pulsatile administration of human menopausal gonadotropins. PMID- 1900491 TI - Effect of pancreatic polypeptide, thyrotropin-releasing hormone, and glucagon on plasma amino acid uptake by human pancreas. AB - The effects of pancreatic polypeptide, thyrotropin-releasing hormone, and glucagon on plasma amino acid uptake by the exocrine pancreas were studied in 12 healthy volunteers aged 22-31 years. Pancreatic amino acid uptake was determined by measuring free plasma amino acid concentration before and during pancreatic stimulation with cerulein (50 ng/kg.h). The administration of this peptide caused a significant decrease (by 14%-20%) in plasma amino acid concentration. Pancreatic polypeptide and thyrotropin-releasing hormone, given at respective doses of 195 pmol/kg.h and 2 micrograms/kg.h, significantly prevented this decrease by 79.3% and 55.8%, respectively. Glucagon, administered at a dose of 7.5 micrograms/kg.h, significantly augmented (by 68.8%) the decreasing effect of cerulein on plasma amino acid concentration. In 2 patients with severe exocrine pancreatic insufficiency, cerulein had no effect on the concentration of plasma amino acids, whereas the addition of glucagon caused a marked decrease. The results indicate that pancreatic polypeptide and thyrotropin-releasing hormone are able to inhibit plasma amino acid uptake by pancreatic acinar cells; this inhibitory effect could be a mechanism by which these peptides decrease pancreatic enzyme secretion. Glucagon does not seem to affect pancreatic amino acid uptake, at least not under the experimental conditions of this study. The decrease in plasma amino acid concentration following glucagon administration was likely the result of the stimulation of amino acid uptake by extrapancreatic tissues by this peptide. PMID- 1900492 TI - Pretranslational regulation of albumin synthesis in tumor-bearing mice. The role of anorexia and undernutrition. AB - Hepatic albumin synthesis, serum albumin turnover, and hepatic albumin messenger RNA (mRNA) content were evaluated in mice bearing a transplantable low differentiated tumor (MCG 101). Results obtained on tumor-bearing mice were compared with results obtained from non-tumor-bearing animals that were either freely fed, food restricted so that their body composition was similar to tumor bearing animals (pair-weighed), fed a protein-free diet for 5 days, or fasted for 48 hours. Tumor-bearing animals became hypoalbuminemic (33 +/- 5 vs. 44 +/- 3 g/L in freely fed mice), which could be explained by both depressed albumin synthesis (1.95% +/- 0.20% vs. 2.67% +/- 0.27%/h in freely fed mice) and increased albumin degradation. Pair-weighed and protein-calorie malnourished controls had reductions in albumin synthesis (1.81% +/- 0.18% and 1.67% +/- 0.17%/h, respectively) similar to tumor-bearing animals, and the starved controls had the lowest synthetic rates (1.07% +/- 0.10%/h). Albumin degradation was increased only in tumor-bearing animals. Hepatic albumin mRNA in undernourished animals was less (tumor bearing, 32% +/- 5%; pair weighed, 47% +/- 4%; 48 hours fasted, 18% +/- 2%; and protein-calorie malnourished, 26% +/- 3%) than 50% of the mRNA content in the livers of freely fed control mice. Messenger RNA-directed synthesis of albumin in vitro was also depressed to a variable degree in tumor bearing and malnourished non-tumor-bearing controls. The hypoalbuminemia in tumor bearing animals could not be prevented by daily injections of a prostaglandin synthesis inhibitor (indomethacin, 1 microgram/g body wt), but the hepatic acute phase protein serum amyloid P decreased from 157 +/- 12 to 103 +/- 9 micrograms/mL in indomethacin-treated tumor-bearing mice (P less than 0.01). It is concluded that increased albumin degradation seen in tumor-bearing animals cannot be explained by associated malnutrition, whereas tumor-associated malnutrition can explain to a large extent the depressed albumin synthesis. Decreased albumin synthesis in tumor-bearing animals correlated in part with a decreased quantity of liver albumin mRNA. The results of the current study are consistent with either a reduced transcription of the albumin gene or a change in albumin mRNA processing and stability communicated by anorexia and malnutrition. PMID- 1900493 TI - Developmental distribution of female-specific Sex-lethal proteins in Drosophila melanogaster. AB - The binary switch gene Sex-lethal (Sxl) must be on in females and off in males to allow the proper elaboration of the appropriate sexual developmental pathway in Drosophila melanogaster. Previous studies suggested a mechanism in which the on/off regulation of Sxl occurs post-transcriptionally at the level of RNA splicing. A critical prediction of this model is that functional Sxl proteins are absent in males but present in females. In this report we show that the expected full-length proteins are only present in female animals. Multiple forms of Sxl protein are found in females, some of which are expressed in a stage- and tissue specific pattern. Consistent with a role of Sxl proteins in regulating alternate splicing, the proteins are localized in the nucleus where they exhibit a punctate staining pattern. Surprisingly, several minor Sxl proteins appear to be present in specific tissues of both sexes of adults. The possible origin of these species is discussed. We also show that Sxl expression in the early embryo is sex specific and depends on maternal daughterless and zygotic sisterless-b activity in accordance with the established roles of these genes as positive regulators of Sxl. The onset of Sxl expression in the germ line occurs later than that in the soma. PMID- 1900494 TI - Forespore-specific transcription of a gene in the signal transduction pathway that governs Pro-sigma K processing in Bacillus subtilis. AB - We present studies on the regulation of a developmental gene (spoIVB) whose product is required at a late stage of morphogenesis during the process of sporulation in Bacillus subtilis. Earlier work implicated the spoIVB gene product in a signal-transduction pathway that governs the conversion of pro-sigma K to the mature and active form of the mother cell sigma factor, sigma K, in response to a signal generated within the forespore chamber of the sporangium. We now show that (1) spoIVB is induced at the engulfment stage of sporulation, (2) this transcription is restricted to the forespore, and (3) spoIVB is under the direct control of the forespore sigma factor sigma G. The discovery that spoIVB is a forespore-expressed gene suggests that the spoIVB gene product, or a developmental event under its control, triggers the processing of pro-sigma K and thereby mediates the coupling of sigma K-directed gene expression in the mother cell to sigma G-directed gene expression in the forespore. We also show that spoIVB transcription is partially dependent on the action of the mother cell regulatory gene spoIIID, a finding that suggests that the transcription of certain forespore-expressed genes is influenced by events in the mother cell. PMID- 1900495 TI - Mutations in the guanine nucleotide-binding domains of a yeast G alpha protein confer a constitutive or uninducible state to the pheromone response pathway. AB - Several domains of guanine nucleotide-binding proteins are conserved and form the guanine nucleotide-binding pocket. Mutations in these domains in EF-Tu, ras, and Gas have been shown to result in informative phenotypes. We made several analogous changes in SCG1, which encodes the alpha subunit of the G protein involved in pheromone response in yeast. The scg1Lys388 and scg1Ala391 mutations resulted in severe growth and cell morphology defects; this phenotype is similar to the null phenotype and results from constitutive activation of the pheromone response pathway. On the basis of the model for the action of the yeast G protein, the effect of these mutations is consistent with the effect of analogous mutations in ras, which result in a transforming phenotype. The SCG1Ala322 mutation resulted in pheromone response and mating defects. This effect is similar to the effect of the analogous G alpha s mutation, which results in a defect in stimulation of adenylate cyclase. The scg1Val50 mutation, which is analogous to the transforming mutation rasVal12, resulted in multiple effects, including defects in growth, cell morphology, and mating. Some of our results and interpretations are different from previously published results of others for the same mutation in SCG1; specifically, our gene replacement of this mutation resulted in high basal activation of the pheromone response pathway, consistent with a GTPase defect, which was not seen previously with scg1Val50 on a low-copy plasmid. Implications of these phenotypes are discussed. PMID- 1900496 TI - New report looks at product cost-effectiveness. PMID- 1900497 TI - Genetic mechanisms of early neurogenesis in Drosophila melanogaster. PMID- 1900498 TI - Change of paracellular permeability of ocular surface epithelium by vitamin A deficiency. AB - Dietary vitamin A deficiency in young rabbits caused advanced squamous metaplasia with keratinization of conjunctival epithelium and concomitant reduced paracellular permeability to 3H-mannitol. Both morphologic and permeability changes were reversed with systemic administration of vitamin A. In adult rabbits, vitamin A deficiency caused milder changes of goblet cell loss and increased cellular stratification in conjunction with reduced permeability in the conjunctiva-like epithelium that covers the vascularized cornea after chemical injury with n-heptanol. Topically applied retinoid (tretinoin 0.1%) did not affect the morphology and permeability of the normal corneal or conjunctival epithelium of rabbits that were not vitamin A deficient. These studies showed that altered permeability is associated with the epithelial abnormality during vitamin A deficiency and helped clarify the physiologic function of retinoids in the ocular surface epithelia in the nondeficient state. PMID- 1900499 TI - Pseudomonas attachment to low-water and high-water, ionic and nonionic, new and rabbit-worn soft contact lenses. AB - The authors determined the attachment of a single strain of Pseudomonas aeruginosa to seven brands of hydrogel soft contact lenses (SCLs): nonionic, low water (polymacon and crofilcon); nonionic, high-water (lidofilcon); ionic, high water (bufilcon, etafilcon, and perfilcon); and surface-neutralized, high-water (bufilcon). The lenses were exposed to a 1 X 10(8) colony-forming units (CFU)/ml P. aeruginosa suspension either when new and sterile or after 24 hr of continuous wear in rabbit eyes. Quantitative scanning electron microscopy showed that, regardless of lens type, significantly fewer bacteria attached to worn than to new SCLs (P less than 0.05). The bacterial attachment on new, unworn SCLs was significantly lower (Wilcoxon rank-sum test) (P less than 0.05) on polymacon and crofilcon than on all other lenses tested except perfilcon; on etafilcon than on bufilcon; and on perfilcon than on all SCLs tested except polymacon. The bacterial attachment on rabbit-worn SCLs was significantly lower (P less than 0.05) on polymacon than on all other lenses tested except crofilcon and perfilcon; on crofilcon than on bufilcon; on lidofilcon and on surface neutralized bufilcon than on crofilcon and perfilcon; on etafilcon than on crofilcon, bufilcon, and perfilcon; and on perfilcon than on crofilcon and bufilcon. The results did not show a consistent relationship between hydration and surface charge and P. aeruginosa adherence. Among the SCLs tested, no one lens had a decisive advantage over another, because all, both new and worn, can bind amounts of P. aeruginosa that could potentially produce bacterial keratitis on predisposed eyes. PMID- 1900500 TI - Alloreactive lymphoid infiltrates in human heart transplants. Loss of class II directed cytotoxicity more than 3 months after transplantation. AB - From 535 endomyocardial biopsies (87 heart transplant recipients) 283 cell cultures could be generated. All cultures tested contained T lymphocytes and in most cases CD4 was the predominant phenotype at any time posttransplant. A significantly higher proportion of CD8-dominated cultures was found among cultures from biopsies without myocytolysis. In the first 3 months post transplant 57% of cultures showed cytotoxicity against both class I and class II mismatched donor major histocompatibility complex (MHC) antigens, changing to an incidence of 33% at greater than 90 days. This proved to be due to a significant decrease in the number of cultures with human leukocyte antigen class II-directed cytotoxicity. This study shows that early after transplantation a heart transplant is infiltrated with activated donor-specific cytotoxic T cells which recognize a broad spectrum of mismatched donor MHC antigens, and that in time this spectrum becomes more restricted. PMID- 1900501 TI - Production of 2-methyl-4[3H]-quinazolinone, an inhibitor of poly(ADP-ribose) synthetase, by bacterium. PMID- 1900502 TI - Purification and characterization of the hydrogen uptake hydrogenase from the hyperthermophilic archaebacterium Pyrodictium brockii. AB - Pyrodictium brockii is a hyperthermophilic archaebacterium with an optimal growth temperature of 105 degrees C. P. brockii is also a chemolithotroph, requiring H2 and CO2 for growth. We have purified the hydrogen uptake hydrogenase from membranes of P. brockii by reactive red affinity chromatography and sucrose gradient centrifugation. The molecular mass of the holoenzyme was 118,000 +/- 19,000 Da in sucrose gradients. The holoenzyme consisted of two subunits by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The large subunit had a molecular mass of 66,000 Da, and the small subunit had a molecular mass of 45,000 Da. Colorometric analysis of Fe and S content in reactive red-purified hydrogenase revealed 8.7 +/- 0.6 mol of Fe and 6.2 +/- 1.2 mol of S per mol of hydrogenase. Growth of cells in 63NiCl2 resulted in label incorporation into reactive red-purified hydrogenase. Growth of cells in 63NiCl2 resulted in label incorporation into reactive red-purified hydrogenase. Temperature stability studies indicated that the membrane-bound form of the enzyme was more stable than the solubilized purified form over a period of minutes with respect to temperature. However, the membranes were not able to protect the enzyme from thermal inactivation over a period of hours. The artificial electron acceptor specificity of the pure enzyme was similar to that of the membrane-bound form, but the purified enzyme was able to evolve H2 in the presence of reduced methyl viologen. The Km of membrane-bound hydrogenase for H2 was approximately 19 microM with methylene blue as the electron acceptor, whereas the purified enzyme had a higher Km value. PMID- 1900503 TI - Isolation of the braZ gene encoding the carrier for a novel branched-chain amino acid transport system in Pseudomonas aeruginosa PAO. AB - The braZ gene for a novel branched-chain amino acid transport system in Pseudomonas aeruginosa PAO was isolated and characterized. Determination of the nucleotide sequence showed that the braZ gene comprises 1,311 nucleotides specifying a protein of 437 amino acids. Hydropathy analysis suggested that the product is an integral membrane protein with 12 membrane-spanning segments. The amino acid sequence showed extensive homology to those of the braB and brnQ gene products, branched-chain amino acid carriers of P. aeruginosa and Salmonella typhimurium, respectively. By using the T7 RNA polymerase-promoter system, the braZ gene product was identified as a protein of an apparent Mr of 34,000 on a sodium dodecyl sulfate-polyacrylamide gel. Properties of the transport system encoded by braZ were studied by using P. aeruginosa PAO3537, defective in both the high- and low-affinity branched-chain amino acid transport systems (LIV-I and LIV-II, respectively). The transport system encoded by braZ was found to be another effective branched-chain amino acid transport system in P. aeruginosa PAO and was thus designated as LIV-III. This system is specific for isoleucine and valine, giving the same Km value of 12 microM for these amino acids. The system was found, however, to have a very low affinity for leucine, with a Km value of 150 microM, which contrasts with the substrate specificities of LIV-I and LIV-II. PMID- 1900504 TI - Isolation and complementation of nitrogen fixation mutants of the cyanobacterium Anabaena sp. strain PCC 7120. AB - Approximately 140 mutants of Anabaena sp. strain PCC 7120 unable to grow aerobically on media lacking fixed nitrogen (Fix-) were isolated after mutagenesis with diethyl sulfate and penicillin enrichment. A large cosmid library of wild-type Anabaena sp. strain PCC 7120 DNA was constructed in a mini RK-2 shuttle vector, and seven mutants representing several morphologically abnormal heterocyst phenotypes were complemented. One of these mutants, 216, failed to differentiate heterocysts. All of these mutants except 216 reduced acetylene under anaerobic conditions, indicating that they are not defective in nitrogen fixation per se. Several cosmids were isolated from each complemented mutant and in most cases showed similar restriction patterns. Comparisons of the complementing cosmids from mutant 216 and two other phenotypically distinct mutants by restriction enzyme analysis identified a common region. This region, when present in either a cosmid or a 9.5-kb NheI subclone, is capable of efficiently complementing all three mutants. A 2.4-kb subclone of this region complements mutant 216 only. PMID- 1900505 TI - The Bacillus subtilis spo0J gene: evidence for involvement in catabolite repression of sporulation. AB - Previous observations concerning the ability of the Bacillus subtilis bacteriophages SP10 and PMB12 to suppress mutations in spo0J and to make wild type sporulation catabolite resistant suggested that spo0J had a role in catabolite repression of sporulation. This suggestion was supported in the present report by the ability of the catabolite-resistant sporulation mutation crsF4 to suppress a Tn917 insertion mutation of the B. subtilis spo0J locus (spo0J::Tn917 omega HU261) in medium without glucose. Although crsF4 and SP10 made wild-type B. subtilis sporulation catabolite resistant, neither crsF4 nor SP10 caused a mutant with spo0J::Tn917 omega HU261 to sporulate in medium with glucose. Sequencing the spo0J locus revealed an open reading frame that was 179 codons in length. Disruption of the open reading frame resulted in a sporulation negative (Spo-) phenotype that was similar to those of other spo0J mutations. Analysis of the deduced amino acid sequence of the spo0J locus indicated that the spo0J gene product contains an alpha-helix-turn-alpha-helix unit similar to the motif found in lambda Cro-like DNA-binding proteins. PMID- 1900506 TI - Distribution of folates and modified folates in extremely thermophilic bacteria. AB - Analyses were made of the structures and levels of folates and modified folates present in extremely thermophilic bacteria. These procedures involved the chemical analysis of products resulting from the oxidative cleavage of the 6 substituted, folatelike tetrahydropterins present in the cells. Air-oxidized cell extracts of extreme thermophiles from two members of the archaebacterial order Thermococcales, Thermococcus celer and Pyrococcus furiosus, contained only 7 methylpterin, indicating that these cells contain a modified folate with a methylated pterin. Cell extracts also contained 6-acetyl-7-methyl-7,8 dihydropterin, another product derived from the oxidative cleavage of a dimethylated folate, demonstrating that both the C-7 and C-9 carbons of the pterin were methylated. Extracts, however, contained neither p aminobenzoylpolyglutamates nor methaniline, the oxidative cleavage products of folates and methanopterin, respectively, indicating that they contain a previously undescribed C1 carrier(s). On the basis of the level of the 7 methylpterin isolated, the levels of modified folate were 2 to 10 times higher than those typically found in mesophilic bacteria and 10 to 100 times less than the level of methanopterin found in the methanogenic bacteria. Oxidized cell extracts of Sulfolobus spp. of the archaebacterial order Sulfolobales contained only pterin, and, like members of the order Thermococcales, they contained neither-p-aminobenzoylpolyglutamates nor methaniline. Oxidized cell extracts of the extreme thermophiles Pyrobaculum sp. strain H10 and Pyrodictium occultum, from the archaebacterial orders Thermoproteales and Pyrodictiales, respectively, and Thermotoga maritima from the eubacterial order Thermotogales, contained pterin and p-aminobenzoylpolyglutamates, indicating that these cells contained unmodified folates. The levels of p-aminobenzoylpolyglutamates in these archaebacterial cell extracts indicate that the folates were present in the cells at levels 4 to 10 times higher than generally found in those mesophilic eubacteria which do not folates in energy metabolism. The levels and chain lengths of the of p-aminobenzoylpolyglutamates present in Thermotoga maritima were typical of those found in mesophilic eubacteria. PMID- 1900507 TI - Effect of promoter mutations and upstream deletions on the expression of genes coding for small, acid-soluble spore proteins of Bacillus subtilis. AB - The sspB and sspE genes code for major small, acid-soluble proteins of Bacillus subtilis spores and are transcribed during sporulation by RNA polymerase containing sigma G. Analysis of the expression in vivo and the sigma G-dependent transcription in vitro of sspB and sspE genes carrying upstream deletions or point mutations in -10 and -35 promoter regions is consistent with sigma G being the only major transcriptional regulator of these genes. These data also provide information on the residues in -10 and -35 regions which are most important for sigma G recognition. PMID- 1900508 TI - Expression of endogenous and foreign ribulose 1,5-bisphosphate carboxylase oxygenase (RubisCO) genes in a RubisCO deletion mutant of Rhodobacter sphaeroides. AB - A Rhodobacter sphaeroides ribulose 1,5-bisphosphate carboxylase-oxygenase (RubisCO) deletion strain was constructed that was complemented by plasmids containing either the form I or form II CO2 fixation gene cluster. This strain was also complemented by genes encoding foreign RubisCO enzymes expressed from a Rhodospirillum rubrum RubisCO promoter. In R. sphaeroides, the R. rubrum promoter was regulated, resulting in variable levels of disparate RubisCO molecules under different growth conditions. Photosynthetic growth of the R. sphaeroides deletion strain complemented with cyanobacterial RubisCO revealed physiological properties reflective of the unique cellular environment of the cyanobacterial enzyme. The R. sphaeroides RubisCO deletion strain and R. rubrum promoter system may be used to assess the properties of mutagenized proteins in vivo, as well as provide a potential means to select for altered RubisCO molecules after random mutagenesis of entire genes or gene regions encoding RubisCO enzymes. PMID- 1900509 TI - A unique repetitive DNA sequence in the Myxococcus xanthus genome. AB - We found a novel type of repetitive DNA sequence in the Myxococcus xanthus genome. The first repetitive sequence is located in the spacer region between the ops and tps genes. We cloned five other repetitive sequences using the first repetitive sequence as a probe and determined their nucleotide sequences. Comparison of these sequences revealed that the repetitive sequences consist of a 87-bp core sequence and that some clones share additional homology on their flanking regions. PMID- 1900511 TI - Structurally conserved water molecules in ribonuclease T1. AB - In the high resolution (1.7-1.9 A) crystal structures of ribonuclease T1 (RNase T1) in complex with guanosine, guanosine 2'-phosphate, guanylyl 2',5'-guanosine, and vanadate, there are 30 water sites in nearly identical (+/- 1 A) positions that are considered conserved. One water is tightly bound to Asp76(O delta), Thr93(O gamma), Cys6(O), and Asn9(N); another bridges two loops by hydrogen bonding to Tyr68(O eta) and to Ser35(N), Asn36(N); a loop structure is stabilized by two waters coordinated to Gly31(O) and His27(N delta), and by water bound to cis-Pro39(O). Most notable is a hydrogen-bonded chain of 10 water molecules. Waters 1-5 of this chain are inaccessible to solvent, are anchored at Trp59(N), and stitch together the loop formed by segments 60-68; waters 5-8 coordinate to Ca2+, and waters 9 and 10 hydrogen-bond to N-terminal side chains of the alpha helix. The water chain and two conserved water molecules are bound to amino acids adjacent to the active site residues His40, Glu58, Arg77, and His92; they are probably involved in maintaining their spatial orientation required for catalysis. Water sites must be considered in genetic engineering; the mutation Trp59Tyr, which probably influences the 10-water chain, doubles the catalytic activity of RNase T1. PMID- 1900510 TI - Myxococcus xanthus protein C is a major spore surface protein. AB - Fruiting body formation in Myxococcus xanthus involves the aggregation of cells to form mounds and the differentiation of rod-shaped cells into spherical myxospores. The surface of the myxospore is composed of several sodium dodecyl sulfate (SDS)-soluble proteins, the best characterized of which is protein S (Mr, 19,000). We have identified a new major spore surface protein called protein C (Mr, 30,000). Protein C is not present in extracts of vegetative cells but appears in extracts of developing cells by 6 h. Protein C, like protein S, is produced during starvation in liquid medium but is not made during glycerol induced sporulation. Its synthesis is blocked in certain developmental mutants but not others. When examined by SDS-polyacrylamide gel electrophoresis, two forms of protein C are observed. Protein C is quantitatively released from spores by treatment with 0.1 N NaOH or by boiling in 1% SDS. It is slowly washed from the spore surface in water but is stabilized by the presence of magnesium. Protein C binds to the surface of spores depleted of protein C and protein S. Protein C is a useful new marker for development in M. xanthus because it is developmentally regulated, spore associated, abundant, and easily purified. PMID- 1900512 TI - A highly reactive beta-galactosidase (Escherichia coli) resulting from a substitution of an aspartic acid for Gly-794. AB - The beta-galactosidases of several mutagenized strains of Escherichia coli K12 which grew on lactobionate were found to be heat labile. Sequence analysis of the lacZ gene (ligated into Bluescript) of one of these strains (E. coli REH4) showed that the only change in the amino acid sequence was a substitution of an Asp for Gly-794. This change caused a dramatic increase of the activity when lactose was the substrate. The kcat of the purified enzyme from E. coli REH4 (G794D-beta galactosidase) with lactose as the substrate was five to six times as large as the kcat of the normal enzyme with lactose. Purified G794D-beta-galactosidase was, however, less stable to heat and also to chymotrypsin (which cleaves next to Trp-585) than was normal beta-galactosidase. G794D-beta-Galactosidase bound substrates and substrate analog inhibitors less well than did normal beta galactosidase while planar transition state analog inhibitors were more strongly bound. The ability to bind 2-amino-D-galactose (a positively charged transition state analog inhibitor) was either unaltered or was decreased somewhat. The data showed that the alteration in structure caused an increase in the value of k2 (the rate constant for the step in which the glycosidic bond is cleaved) with each substrate tested (the increase was at least 25-fold when lactose was the substrate) while k3 was decreased about 4-fold (k3 is the rate constant for the common hydrolysis step with each substrate). Since k2 is rate determining when lactose is the substrate of the normal enzyme, the increase in k2 resulted in a large increase in rate despite the fact that the value of k3 decreased. Large rate increases were not found with the other two substrates because the k2 values were not increased by large factors and because the decrease in the value of k3 negated the effects of the increased k2 values. The destabilization of the substrate binding coupled with a stabilization of the binding of a planar transition state is a possible cause of the significant increase in the value of k2 and of the enhanced activity with lactose. PMID- 1900513 TI - A novel serine protease with vasoconstrictor activity coded by the kallikrein gene S3. AB - A fraction separated from rat submandibular gland homogenates was found to contain a potent vasoconstrictor when tested on isolated rabbit aortic rings. The vasoconstrictor was purified by a series of chromatographic steps. The purified compound (2.77 x 10(-9) M) induced 40% of the maximum contractile response to 60 mM KCl. Constriction was slow in onset, long-lasting, rinse-resistant, and unchanged by de-endothelialization; in addition, it was dose-related and inhibited by both EGTA and verapamil, but it was not affected by DUP753, an angiotensin II receptor antagonist. The compound was found to be a protein having a pI of 7.36 and a molecular weight of approximately 29,000 and exhibiting partial immunologic identity to rat glandular kallikrein and rat tonin. After 2 mercaptoethanol treatment, it separated into heavy (approximately 19,900) and light (approximately 10,700) chains having amino-terminal sequences of AY(X)HNNDLMLL and VVGGYN(X)ETNSQ, respectively. We found that they correspond to the amino-terminal and internal sequence of a previously unidentified kallikrein like serine protease whose mRNA, named S3, has been found in the rat submandibular gland and prostate. The vasoconstrictor is able to hydrolyze t butoxycarbonyl-valine-proline-arginine-methylcoumarin amide (a thrombin substrate), although its Kcat/Km was only 0.02% that of rat thrombin. Both vasoconstrictor and enzymatic activity on t-butoxycarbonyl-valine-proline arginine-methylcoumarin amide were completely suppressed by amidinophenylmethylsulfonyl fluoride and soybean trypsin inhibitor; however, they were unaffected by hirudin, a thrombin inhibitor. At pH 6.5, it released angiotensin II when incubated with sheep angiotensinogen, although it had approximately one-tenth the activity of tonin. The submandibular enzymatic vasoconstrictor is a kallikrein-like enzyme, having some properties of both tonin and thrombin. It directly contracts vascular smooth muscle, acting via a mechanism that requires intact enzymatic activity. PMID- 1900514 TI - Transcriptional regulation and localization of the tissue-specific induction of epoxide hydrolase by lead acetate in rat kidney. AB - Intraperitoneal administration of lead acetate to male Sprague-Dawley rats resulted in the tissue-specific transcriptional activation of the microsomal epoxide hydrolase gene in kidney. This response was followed by a 15-fold increase in the level of kidney epoxide hydrolase mRNA, while no change in mRNA level was noted in liver. Treated animals also showed no increase in mRNA levels for NADPH-cytochrome P-450 oxidoreductase, cytochrome P-450b/e, cytochrome P 450PCN (where PCN is pregnenolone 16 alpha-carbonitrile), or serum albumin in either kidney or liver. Immunoquantitation of the enzyme revealed a 16-fold increase in kidney upon treatment with lead acetate, but significant changes in epoxide hydrolase levels were not noted in liver, heart, spleen, lung, small intestine, or testis. The enzymatic activity for liver and kidney paralleled the immunochemical results; however, the activity increase in kidney was only one third of the increase noted for total enzyme protein. Immunohistochemical analysis of epoxide hydrolase protein in sections of rat kidney demonstrated that in lead acetate-treated animals there was a marked increase in staining of the cytoplasm of the proximal tubular cells in the outer cortex as compared with kidneys from control animals. In contrast, considerable protein was also localized to collecting ducts, but no change was evident in the content of the epoxide hydrolase gene product in these structures in control and lead acetate treated animals. Immunohistochemical differences were not noted between livers from control and lead-treated animals. Furthermore, the staining patterns for NADPH-cytochrome P-450 oxidoreductase were the same for control and treated animals in both kidney and liver. Quantitative measurements of lead uptake by various rat tissues showed liver, spleen, and small intestine reaching a maximum of approximately 12,000 ng of lead/g of dry tissue at 8, 8, and 16 h, respectively, while kidney, lung, and testis peaked (approximately 3,000 ng of lead/g of dry tissue) at 16, 16, and 12 h, respectively. PMID- 1900515 TI - Cathepsin B efficiently activates the soluble and the tumor cell receptor-bound form of the proenzyme urokinase-type plasminogen activator (Pro-uPA). AB - Action of purified human cathepsin B on recombinant single-chain urokinase-type plasminogen activator (pro-uPA) generated enzymatically active two-chain uPA (HMW uPA), which was indistinguishable by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot from plasmin-generated HMW-uPA and from elastase or thrombin-generated inactive two-chain urokinase-type plasminogen activator. Preincubation of cathepsin B with E-64 (transepoxysuccinyl-L-leucylamino- (4 guanidino)butane, a potent inhibitor for cathepsin B) prior to the addition of pro-uPA prevented the activation of pro-uPA. The cleavage site within the cathepsin B-treated urokinase-type plasminogen activator (uPA) molecule, determined by N-terminal amino acid sequence analysis, is located between Lys158 and Ile159. Pro-uPA is cleaved by cathepsin B at the same peptide bond that is cleaved by plasmin or kallikrein. Binding of cathepsin B-activated pro-uPA to the uPA receptor on U937 cells did not differ from that of enzymatically inactive pro uPA, indicating an intact receptor-binding region within the growth factor-like domain of the cathepsin B-treated uPA molecule. Not only soluble but also tumor cell receptor-bound pro-uPA could be efficiently cleaved by cathepsin B to generate enzymatically active two-chain uPA. Thus, cathepsin B can substitute for plasmin in the proteolytic activation of pro-uPA to enzymatically active HMW-uPA. In contrast, no significant activation of pro-uPA by cathepsin D was observed. As tumor cells may produce both pro-uPA and cathepsin B, implications for the activation of tumor cell-derived pro-uPA by cellular proteases may be considered. PMID- 1900516 TI - High resolution analysis of functional determinants on human tissue-type plasminogen activator. AB - Sixty-four variants of human tissue-type plasminogen activator (tPA) were produced using recombinant DNA techniques. Charged residues were converted to alanine in clusters of from one to four changes per variant; these clusters spanned all the domains of the molecule. The variants were expressed by mammalian cells and were analyzed for a variety of properties. Variants of tPA were found that had reduced activity with respect to each tested property; in a few cases increased activity was observed. Analysis of these effects prompted the following conclusions: 1) charged residues in the nonprotease domains are less involved in fibrin stimulation of tPA activity than those in the protease domain, and it is possible to increase the fibrin specificity (i.e. the stimulation of tPA activity by fibrin compared to fibrinogen) by mutations at several sites in the protease domain; 2) the difference in enzymatic activity between the one- and two-chain forms of tPA can be increased by mutations at several sites on the protease domain; 3) binding of tPA to lysine-Sepharose was affected only by mutations to kringle-2, whereas binding to fibrin was affected most by mutations in the other domains; 4) clot lysis was influenced by mutations in all domains except kringle 2; 5) sensitivity to plasminogen activator inhibitor-1 seems to reside exclusively in the region surrounding residue 300. A model of the tPA protease domain has been used to map some of the critical residues and regions. PMID- 1900517 TI - Biosynthesis in vitro of GlcA beta 1-3nLcOse4Cer by a novel glucuronyltransferase (GlcAT-1) from embryonic chicken brain. AB - A novel glucuronyltransferase (GlcAT-1) has been detected in embryonic chicken brains. This enzyme catalyzes the biosynthesis in vitro of glucuronic acid containing glycolipids starting from neolactotetraosylceramide (nLcOse4Cer) and neolactohexaosylceramide (nLcOse6Cer). The activity is present primarily in the Golgi-rich membrane fraction and can be extracted (60%) from the membrane using a neutral detergent, Nonidet P-40, at pH 7.0. The detergent-solubilized GlcAT-1 is stable (70%) at -20 degrees C for at least 4 months. Both membrane-bound GlcAT-1 and solubilized GlcAT-1 show similar pH optima, 6.5-7.0, in HEPES buffer. The Km values were 15 and 200 microM with UDP-[14C] GlcA and nLcOse4Cer, respectively, when the detergent-solubilized supernatant fraction was used as enzyme source. The purified 14C radioactive product that comigrated with chemically characterized GlcA beta 1-3nLcOse4Cer (GlcA-nLc4) also yielded a positive immunostain with monoclonal antibody (human IgM-RI). The anomeric linkage was established as beta-linked GlcA to the terminal galactose of the substrate, as evidenced by 90-99% cleavage of the terminal [14C] GlcA by purified Helix pomatia and limpet glucuronidases. Permethylation studies of the radioactive product obtained from [6-3H]Gal beta 1-4LcOse3Cer and non-radioactive UDP-GlcA showed the presence of 2,4,6-tri-O-methylgalactose in the hydrolyzed enzymatic product. These studies established the structure of the biosynthesized product from nLcOse4Cer as GlcA beta 1-3Gal beta 1-4 GlcNAc beta 1-3Gal beta 1-4Glc-ceramide. PMID- 1900518 TI - Cholinergic response of isolated rat atria to recombinant rat interferon-gamma. AB - Addition of recombinant rat interferon-gamma (IFN-gamma) to beating rat atria decreased the contractile strength in a dose-dependent manner. The effect was specific of IFN-gamma since it was abrogated by monoclonal anti-rat IFN-gamma. It required the activation of the cholinergic system of the heart as inhibition of both nicotinic (10(-7) M hexametonium) and muscarinic cholinoceptors (10(-7) M atropine) prevented the reaction. Hemicholinium (2 x 10(-5) M) and tetrodotoxin (5 x 10(-7) M) also reduced the response. Likewise, IFN-gamma potentiated the action of the muscarinic agonist carbachol. IFN-gamma simulated the biological effect of cholinergic agonists because: (a) it increased cGMP formation; (b) it decreased cAMP formation; and (c) it reduced heart contractility at doses that can be considered physiologic. IFN-gamma also modified the muscarinic receptor by interfering with the binding of the radiolabelled antagonist quinuclidinyl benzilate [( 3H]QNB). It is suggested that IFN-gamma binding to IFN-gamma receptors in the heart may lead to a cholinergic response by interaction of both receptor systems on the surface of atrial cells. PMID- 1900519 TI - Fixation of the Austin osteotomy with bioresorbable pins. AB - Clinical trials were conducted at the Foot Clinics of New York, testing the use of the Johnson & Johnson Orthosorb absorbable pins as an integral absorbable form of fixation of the Austin osteotomy. Two Orthosorb pins were inserted across the osteotomy from dorsal to plantar. Patients were placed in a plaster splint and allowed to walk with weightbearing as tolerated within 2 weeks of the procedure. A protocol was designed to include a 6-month follow-up with regularly scheduled postoperative examinations. These examinations included a review of pain, walking ability, edema, and measurements of dorsiflexion and plantarflexion. No complications have occurred in this patient population. This study has shown that for a selected group of surgical candidates, Orthosorb bioresorbable pins are an effective form of fixation for the Austin osteotomy. PMID- 1900520 TI - Detection of mycobacterial antigen by dot blot assay in the cerebrospinal fluid of patients with tuberculous meningitis. PMID- 1900521 TI - Diabetes mellitus presenting with ketoacidosis following pentamidine therapy in patients with acquired immunodeficiency syndrome. AB - Patients with acquired immunodeficiency syndrome (AIDS) are at risk from many endocrine complications. Pentamidine has been recognised for its potential to cause symptomatic, and even life-threatening hypoglycaemia. We report two cases of diabetes mellitus presenting with ketoacidosis 3 to 4 months after pentamidine therapy for Pneumocystis carinii pneumonia (PCP), and review our experience of dysglycaemia in 58 patients with AIDS treated with pentamidine. These cases emphasise the potential for severe pancreatic toxicity in patients with AIDS. Hyperglycaemia during pentamidine therapy may be a marker for patients at increased risk of developing diabetes mellitus. PMID- 1900522 TI - Tumor necrosis factor and granulocyte macrophage-colony stimulating factor stimulate human macrophages to restrict growth of virulent Mycobacterium avium and to kill avirulent M. avium: killing effector mechanism depends on the generation of reactive nitrogen intermediates. AB - An avirulent and a virulent strain of Mycobacterium avium were selected on the basis of their growth patterns in human monocyte-derived macrophages. The virulent 7497 M. avium grew progressively in untreated macrophages, whereas the avirulent LR/149 M. avium was killed to a moderate extent by untreated human macrophages (50% of the original infectious inoculum killed 7 days after infection). We set out to investigate the possibility of modulating these growth patterns by cytokine treatment. Application of tumor necrosis factor (TNF) (100 U/ml) led to macrophages restricting significantly the growth of virulent M. avium 7497 (tenfold decrease at 7 days). TNF was also effective at modulating positively the interaction between avirulent LR/149 M. avium and macrophages inasmuch as TNF-treated cells killed 99% of infecting mycobacteria at 7 days. Granulocyte macrophage-colony stimulating factor (GM-CSF) (100-10,000 U/ml) treatment led to macrophages being as mycobacteriostatic for virulent 7497 M. avium as TNF-alpha-treated cells (i.e., tenfold reduction in growth). Treatment of macrophages with both GM-CSF and TNF-alpha was shown to have additive effects on bacteriostatic activity on M. avium. The mechanism of killing of avirulent M. avium by TNF-alpha was shown to be dependent on the generation of reactive nitrogen intermediates, as seen by inhibition of effector mechanisms by NG monomethyl-arginine and arginase. Moreover, there was a correlation between NO2- generation and mycobactericidal activity of macrophages. Addition of superoxide dismutase reversed the killing of avirulent M. avium by untreated or TNF-treated macrophages. This abrogation was also apparent in chronic granulomatous disease (CGD) macrophages, which were inefficient at generating reactive oxygen intermediates. Moreover, macrophages from CGD patients killed avirulent M. avium as efficiently as cells from normal individuals. We conclude from these results that 1) GM-CSF and TNF-alpha, alone or in combination, increase effector functions of macrophages against virulent and avirulent strains of M. avium; 2) reactive nitrogen intermediates seem to be involved in this effector mechanism; and 3) superoxide dismutase protected M. avium against macrophage effector function, seemingly by protecting the bacteria against endogenous superoxide anion. The implications of these findings for host resistance to atypical mycobacteria are discussed. PMID- 1900523 TI - Selective radiation resistance of immunologically induced T cells as the basis for irradiation-induced T-cell-mediated regression of immunogenic tumor. AB - Sublethal, whole-body gamma-irradiation of immunocompetent, but not T cell deficient, mice bearing an established immunogenic tumor results in T-cell mediated complete tumor regression and in long-term host survival. This striking T-cell-dependent immunotherapeutic action of irradiation was paradoxically associated with the destruction of over 90% of host T cells and with a state of severe immunodepression as evidenced by the inability of irradiated mice to reject a tumor allograft. Furthermore, whereas exposure to 500 rads caused regression of a syngeneic tumor implanted 6 days before irradiation, it caused enhanced growth of a different syngeneic tumor growing on the same animal and implanted 1 day before. This ability of irradiation to cause regression of a 6 day tumor, but accelerated growth of a 1 day tumor, was also seen when the tumors were implanted in the reverse order. This means that, between days 1 and 6 of a tumor growth, tumor-specific T cells are converted from a radiosensitive to a highly radioresistant state, almost certainly because of having been activated and inducted into the antitumor immune response. This explanation for the selective radioresistance of effector T cells is based on publications showing that activated, in contrast to resting, T cells are highly radioresistant. Thus irradiation-induced, T-cell-mediated tumor regression depends not only on the destruction of radiosensitive suppressor T cells but also on the selective sparing of radioresistant activated effector T cells that are needed to destroy the tumor in the absence of suppression. PMID- 1900524 TI - Admission by family physicians vs internists. PMID- 1900525 TI - In vivo study of the elimination from rat brain of an intracerebrally formed xenobiotic metabolite, 1-naphthyl-beta-D-glucuronide. AB - Among the drug-metabolizing enzymes present in the rat brain, one form of UDP glucuronyltransferase catalyzes the formation of the polar metabolite 1-naphthyl beta-D-glucuronide from 1-naphthol. We measured the activity of this isoform in different brain regions and showed its heterogeneous distribution. Conjugation activities were found to be the highest in the olfactory bulbs (25.4 nmol/h/mg protein) and lowest in the cerebellum (4.5 nmol/h/mg protein). As the blood-brain barrier prevents the passage of hydrosoluble molecules, we studied in vivo the characteristics of the efflux of labeled 1-naphthyl-beta-D-glucuronide injected into the lateral ventricle and the cortex tissue, using tritiated water and labeled inulin as reference compounds. The results reported here indicate that intracerebrally formed glucuronide is cleared from brain tissue by both diffusion and a saturable efflux process. PMID- 1900526 TI - Output, tissue levels, and synthesis of acetylcholine during and after transient forebrain ischemia in the rat. AB - Biochemical changes in the rat brain cholinergic system during and after 60 min of ischemia were studied using a four-vessel occlusion model. Extracellular acetylcholine (ACh) concentrations in the unanesthetized rat hippocampus markedly increased during ischemia and reached a peak (about 13.5 times baseline levels) at 5-10 min after the onset of ischemia. At 2-5 h after reperfusion, extracellular ACh concentrations were reduced to 64-72% of the levels of controls. ACh levels in the hippocampus, striatum, and cortex decreased significantly during ischemia and exceeded their control values just after reperfusion. A significant increase in hippocampal ACh level after 2 days of reperfusion and a decrease in [14C]ACh synthesis from [14C]glucose in hippocampal slices excised at 2 days after reperfusion were observed. The extracellular concentrations and tissue levels of choline markedly increased after ischemia. These results show that ACh is markedly released into the extracellular space in the hippocampus during ischemia, and they suggest that ACh synthesis is activated just after reperfusion and that cholinergic activity is reduced after 2-48 h of reperfusion in the hippocampus. PMID- 1900527 TI - The iron chelator desferrioxamine (Desferal) retards 6-hydroxydopamine-induced degeneration of nigrostriatal dopamine neurons. AB - A selective increase in content of iron in the pars compacta of the substantia nigra has been implicated in the biochemical pathology of Parkinson's disease. Iron is thought to induce oxidative stress by liberation of oxygen free radicals from H2O2. Because 6-hydroxydopamine (6-OHDA) is thought to induce nigrostriatal dopaminergic neuronal lesions via metal-catalyzed free radical formation, the effect of the iron chelator desferrioxamine was investigated on 6-OHDA-induced dopaminergic neuron degeneration in the rat. Intracerebroventricular injection of 6-OHDA (250 micrograms) caused a 88, 79, and 70% reduction in striatal tissue content of dopamine (DA), 3,4-dihydroxyphenylacetic acid, and homovanillic acid (HVA), respectively, and a 2.5-fold increase in DA release as indicated by the HVA/DA ratio. Prior injection of desferrioxamine (130 ng i.c.v.) resulted in a significant protection (approximately 60%) against the 6-OHDA-induced reduction in striatal DA content and a normalization of DA release. Dopaminergic-related behavioral responses, such as spontaneous movements in a novel environment and rearing, were significantly impaired in the 6-OHDA-treated group. By contrast, the desferrioxamine-pretreated rats exhibited almost normal behavioral responses. The ability of iron chelators to retard dopaminergic neurodegeneration in the substantia nigra may indicate a new therapeutic strategy in the treatment of Parkinson's disease. PMID- 1900528 TI - Cytosolic calcium changes in cultured rat aortic smooth-muscle cells induced by oxyhemoglobin. AB - To clarify the mechanism of contractive effects in arteries caused by oxyhemoglobin, changes in the concentration of cytosolic calcium [( Ca++]i) before and after exposure to oxyhemoglobin were measured in vitro in cultured vascular smooth-muscle cells obtained from rat aorta. This was accomplished by preloading these cells with a fluorescent intracellular Ca++ probe fura-2/AM. Oxyhemoglobin induced a significant elevation of [Ca++]i in vascular smooth muscle cells which was sustained for 10 minutes. This response was completely abolished by chelating extracellular calcium with ethyleneglycol-bis (beta aminoethylether)-N,N'-tetra-acetic acid (EGTA). Oxyhemoglobin induced no accumulation of mass content of inositol 1,4,5-trisphosphate (IP3(1,4,5]. The oxyhemoglobin-induced elevation of [Ca++]i was not blocked by verapamil, a calcium antagonist. Serotonin induced a rapid, transient increase of [Ca++]i followed by a sustained elevation above baseline for 5 minutes. Additions of EGTA or verapamil had a small effect on the peak height of serotonin-induced [Ca++]i elevation, but the [Ca++]i level declined more quickly to the basal level in treated compared with control cells. These results indicate that oxyhemoglobin induced [Ca++]i elevation is caused by the influx of extracellular calcium, which is independent of the verapamil-blocked voltage-gated calcium channel. The long lasting high elevation of [Ca++]i caused by oxyhemoglobin suggests that oxyhemoglobin may contribute to the production of abnormal contractions and/or irreversible damage in vascular smooth-muscle cells. PMID- 1900529 TI - Microinfarction: osmotic BBB opening or microcrystals in infusate? PMID- 1900530 TI - Principles for effective surveys of hunger and malnutrition in the United States. AB - To be effective, the information derived from a survey must be used to make decisions that affect policies and programs. This paper discusses why scientifically sound surveys may not be effective and vice versa. Effectiveness depends on the information being relevant to the decision-maker's understanding of the problem to be solved. To the extent that science contributes to both understanding the problem and providing the information for a decision, the survey will be scientific and effective. The measurement of malnutrition and barriers to communication are not at present the major obstacles to effective scientific surveys relative to hunger and malnutrition in the United States. Rather, the obstacles seem to be poor scientific conceptualization and measurement of hunger, on the one hand, and poor sampling techniques for malnutrition, on the other hand. These frontiers of knowledge have implications for science and policy beyond surveys. The challenge for the American Institute of Nutrition is to recruit the scientific skills need to understand hunger and identify pockets of malnutrition and their causes--scientific skills that go beyond those traditionally associated with nutrition research. PMID- 1900531 TI - Oral candidosis in the elderly in long term hospital care. AB - A total of 137 patients in long term hospital care were interviewed and examined to determine the prevalence, nature and most important causes of oral candidosis in the hospitalized elderly. Oral candidal infection as determined by the imprint culture technique was present in 47% of patients with a further 31% being carriers of Candida. The prevalence of chronic atrophic candidosis in denture wearers was 38%, while 26% of all patients had angular cheilitis, 67% of which had an infective etiology. Microbiologic examination strongly indicated the upper denture as the major source of infection in those with dentures despite the existence of a ward policy which should have encouraged good oral and denture hygiene. PMID- 1900532 TI - A highly specific aldose reductase inhibitor, ethyl 1-benzyl-3-hydroxy-2(5H) oxopyrrole-4-carboxylate, and its congeners. AB - Ethyl 1-benzyl-3-hydroxy-2(5H)-oxopyrrole-4-carboxylate (1, EBPC) is a potent and specific inhibitor of aldose reductase. It was greater than 4000X more potent in its inhibition of rat lens aldose reductase than the closely related rat or pig kidney aldehyde reductase, thus making it the most selective inhibitor of a NADPH dependent carbonyl reductase identified to date. In agreement with this observation, it was found to be a highly potent inhibitor of aldose reductase from rat sciatic nerve with greater than 98% inhibition at 1 microM, but it was practically devoid of activity against aldehyde reductases from rat liver and brain. Inhibition of aldose reductase was mixed type for glyceraldehyde (Ki = 8.0 x 10(-8) M) and noncompetitive for NADPH (Ki = 1.70 x 10(-8) M). Its potential as an in vitro tool to quantitate monomeric aldo/keto reductase activities in crude tissue extracts is presented. Structure-activity relationships emerging from synthetic modifications of EBPC are discussed. Several modifications were found to be active in vitro against aldose reductase from human placenta and in vivo in a rat model of diabetic complications, but none was more potent than EBPC. PMID- 1900534 TI - Structural mechanism for glycogen phosphorylase control by phosphorylation and AMP. AB - The crystal structures of activated R state glycogen phosphorylase a (GPa) and R and T state glycogen phosphorylase b (GPb) complexed with AMP have been solved at 2.9 A, 2.9 A and 2.2 A resolution, respectively. The structure of R state GPa is nearly identical to the structure of sulphate-activated R state GPb, except in the region of Ser14, where there is a covalently attached phosphate group in GPa and a non-covalently attached sulphate group in GPb. The contacts made by the N terminal tail residues in R state GPa at the subunit interface of the functionally active dimer are similar to those observed previously for T state GPa. The quaternary and tertiary structural changes on the T to R transition allow these interactions to be relayed to the catalytic site in R state GPa. The transition from the T state GPb structure to the R state GPa structure results in a change in the N-terminal residues from a poorly ordered extended structure that makes intrasubunit contacts to an ordered coiled conformation that makes intersubunit contacts. The distance between Arg10, the first residue to be located from the N terminus, in R state GPa and T state GPb is 50 A. One of the important subunit-subunit interactions in the dimer molecule involves contacts between the helix alpha 2 and the cap' (residues 35' to 45' that form a loop between the 1st and 2nd alpha helices, alpha 1' and alpha 2' of the other subunit. The prime denotes residues from the other subunit). The interactions made by the N-terminal residues induce structural changes at the cap'/alpha 2 helix interface that lead to the creation of a high-affinity AMP site. The tertiary structural changes at the cap (shifts 1.2 to 2.1 A for residues 35 to 45) are partially compensated by the quaternary structural change so that the overall shifts in these residues after the combined tertiary and quaternary changes are between 0.5 and 1.3 A. AMP binds to R state GPb with at least 100 fold greater affinity and exhibits four additional hydrogen bonds, stronger ionic interactions and more extensive van der Waals' interactions with 116 A2 greater solvent accessible surface area buried compared with AMP bound to T state GPb.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1900533 TI - Antinociceptive (aminoalkyl)indoles. AB - The (aminoalkyl)indole (AAI) derivative pravadoline (1a) inhibited prostaglandin (PG) synthesis in mouse brain microsomes in vitro and ex vivo and exhibited antinociceptive activity in several rodent assays. In vitro structure-activity relationship studies of this new class of PG synthesis inhibitors revealed a correspondence in three respects to those reported for the arylacetic acids: (1) "alpha-methylation" caused an increase in PG inhibitory potency, (2) the (R) alpha-methyl isomer was more active than the S isomer, (3) the hypothesized aroyl group conformation of the 2-methyl derivatives corresponded to the proposed and reported "active" conformations of the aroyl and related aromatic acetic acid derivatives. The 1H NMR chemical shift of the C-4 hydrogen of pravadoline in comparison to the deshielding seen with 50, which lacks a substituent at C-2, suggested that the carbonyl group of pravadoline is located near C-2 but is located near C-4 in 50. Associated with this conformational change of the carbonyl group of 1a is a diminution of PG synthetase inhibitory activity. The results of UV and difference nuclear Overhauser studies of the two compounds were consistent with these conformational assignments. The low eudismic ratios of the alpha-methyl derivatives and the observation that the side chain may be extended by three methylene groups without significant loss of PG inhibitory potency suggests that this class of inhibitors bound less strongly and less selectively to the active site of PG synthetase than do the arylacetic acids. Two AAIs, 1a and 30, were found to be metabolized to the corresponding acetic acid derivatives, both of which inhibited PG synthesis. An exception to the observation that the antinociceptive activity of the AAIs was associated with PG synthetase inhibitory activity was the 1-naphthoyl derivative 67 since neither it nor its acetic acid metabolite 74 inhibited PG synthesis. Yet 67 was antinociceptive in four different rodent assays. This naphthoyl derivative, like opioids, also inhibited electrically stimulated contractions in the mouse vas deferens (MVD) preparation. Unlike opioids, however, the inhibition was not antagonized by naloxone. A subseries of AAIs was identified, of which 67 was prototypic. These compounds lacked PG synthetase inhibitory activity, but their inhibitory potency in MVD preparations correlated roughly with their antinociceptive potency in vivo. Pravadoline was also inhibitory in the MVD. Its antinociceptive activity, therefore, may be a consequence of both its PG synthetase inhibitory potency and another antinociceptive mechanism, the latter associated with its inhibitory potency in the MVD.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1900535 TI - Motif recognition and alignment for many sequences by comparison of dot-matrices. AB - Calculation of dot-matrices is a widespread tool in the search for sequence similarities. When sequences are distant, even this approach may fail to point out common regions. If several plots calculated for all members of a sequence set consistently displayed a similarity between them, this would increase its credibility. We present an algorithm to delineate dot-plot agreement. A novel procedure based on matrix multiplication is developed to identify common patterns and reliably aligned regions in a set of distantly related sequences. The algorithm finds motifs independent of input sequence lengths and reduces the dependence on gap penalties. When sequences share greater similarity, the same approach converts to a multiple sequence alignment procedure. PMID- 1900536 TI - Immunotoxicity of bis(tri-n-butyltin) oxide in the rat. AB - Previous studies in the rat have shown that bis(tri-n-butyltin) oxide (TBTO), used as a biocide, was immunotoxic at dose levels that did not affect other organs. In order to determine a no-effect level, weanling rats were treated for at least 28 consecutive days with TBTO at 0, 0.5, 2, 5, or 50 mg/kg of diet. Studies on clinical chemistry, hematology, pathology, and immune function, that is, plaque-forming cell (PFC) assay, delayed-type hypersensitivity (DTH) response, and the splenic clearance of Listeria monocytogenes, were performed at the end of treatment. No treatment-related effects were noted on clinical chemistry and hematology parameters and on PFC and DTH response, whereas thymic atrophy and impaired clearance of L. monocytogenes were noted only at a dietary concentration of 50 mg/kg. These results confirm the thymus as a target organ of TBTO immunotoxicity. Under the conditions of these experiments the dietary concentration of 5 mg/kg, equivalent to a dose of 0.5 mg/kg body weight, represents a no observed effect level (NOEL) for immunotoxicity in the Sprague Dawley rat. PMID- 1900537 TI - Elevated urinary C-peptide excretion in multiple trauma patients. AB - A simple, indirect method of estimating integrated insulin secretion is the measurement of C-peptide, a byproduct of insulin biosynthesis, in plasma and in 24-hr urine samples. We determined, in 29 severely injured hypermetabolic and highly catabolic multiple trauma patients, the plasma level and daily excretion rate of C-peptide, 48-72 hrs postinjury. Data from a set of eight patients who underwent glucose-based total parenteral feeding for 6 days were analyzed for the course of changes in the excretory pattern of C-peptide and catecholamines. The molar ratio of plasma C-peptide to insulin in the trauma patients was similar to that in unstressed controls, indicating that the rate of hepatic insulin extraction is not appreciably altered due to trauma. This is also evident from a significant correlation (p = 0.001) between the plasma C-peptide and insulin levels. The excretion of C-peptide was elevated to three times the normal both in absolute terms and when normalized to creatinine excretion. This was also accompanied by a twofold increase in the plasma levels, indicating an enhanced secretion rate of C-peptide and hence of insulin in response to trauma. Injury induced insulin resistance does not seem to be due to a decreased insulin secretion. An increase in insulin output would appear to be a significant and desirable response for a continued anabolic stimulus coexistent with the net catabolic phase. Parenteral feeding augmented the excretion of C-peptide and catecholamines and this effect peaked on the fourth day of nutritional therapy. PMID- 1900538 TI - Ipsilateral fracture-dislocation of the hip, knee, and ankle: case report. AB - A case of ipsilateral fracture-dislocation of the hip, knee, and ankle is presented. The patient had no neurovascular compromise or postoperative complications. A review of the literature produced no previous reports of this combination of injuries. PMID- 1900541 TI - From the National Institutes of Health. PMID- 1900539 TI - Human immunodeficiency virus type 1 Tat does not transactivate mature trans acting responsive region RNA species in the nucleus or cytoplasm of primate cells. AB - Human immunodeficiency virus (HIV)-encoded transactivator Tat is essential for viral gene expression and replication. By interacting with a nascent RNA stem loop called the trans-acting responsive region (TAR). Tat increases rates of initiation and/or elongation of HIV transcription. Several reports have also suggested that Tat has additional effects on mature HIV RNA species including modification of primary transcripts in the nucleus and their increased translation in the cytoplasm. These posttranscriptional effects are most pronounced in the Xenopus oocyte. To investigate directly whether Tat has similar effects on viral transcripts in cells that are permissive for HIV replication, we cotransfected and microinjected human and monkey cells with Tat and TAR in the form of DNA or RNA. Whereas Tat transactivated TAR DNA targets, it did not transactivate TAR RNA targets in the nucleus of microinjected cells or in the cytoplasm of transfected cells. We conclude that in cells permissive for viral replication, Tat exerts its effect primarily at the level of HIV transcription. PMID- 1900542 TI - Time for medical audit. PMID- 1900540 TI - Folding, interaction with GRP78-BiP, assembly, and transport of the human immunodeficiency virus type 1 envelope protein. AB - A detailed kinetic and quantitative analysis of the early and late biosynthetic events undergone by the human immunodeficiency virus type 1 envelope protein expressed by a recombinant vaccinia virus was performed. Early folding events that occurred in the endoplasmic reticulum included disulfide bond formation (t1/2 approximately 10 min), folding of envelope protein into a form competent to bind CD4 (t1/2 approximately 15 min), and specific and transient association and dissociation with GRP78-BiP (t1/2 approximately 25 min). After initial folding, envelope protein monomers formed noncovalently associated dimers with high efficiency (t1/2 approximately 30 min). Studies with brefeldin A, a compound that inhibits endoplasmic reticulum-to-Golgi transport, suggested that assembly occurred in the endoplasmic reticulum while cleavage of gp160 into gp120/gp41 subunits occurred in a post-endoplasmic reticulum compartment. Transport to the Golgi was monitored by modification of N-linked sugars to forms partially resistant to endoglycosidase H. The kinetics of endoglycosidase H resistance were nearly identical to the kinetics of gp160 cleavage (t1/2 approximately 80 min). Cleavage efficiency was strongly cell type dependent, ranging from 13 to 70%. By contrast, approximately 50% of the gp120 generated by the cleavage event was shed (t1/2 approximately 120 min) regardless of the cell type used. The results are discussed in terms of the overall biosynthetic pathway of the envelope protein and provide a framework with which to assess the effects of mutations on structure and function. PMID- 1900543 TI - Dubai syndrome in Karachi. AB - This is an attempt to study the effects of migration of earning member (to Gulf States) on the family, specially children left behind. Twenty five families who sought psychiatric help for one of their members were included. A control group (of non-migrant family) attending the out-patient's department was selected for comparison. The wife and children left behind experienced considerable emotional hardship. Twenty two families (88%) reported statistically significant recent maladjustment in 35 children (30%) as compared to control group of twelve families (48%) in 15 children (10%). Undoubtedly the major brunt is faced by the wives but the damage done to children is much less appreciated. This study identifies the current disturbance but the future effects on the personality of other children could manifest much later. PMID- 1900544 TI - Anaesthetic management for atlanto axial subluxation. AB - A number of disease processes including congenital anomalies, malunited odontoid fractures, rheumatoid arthritis and tuberculosis can result in atlanto axial subluxation. The patient population presenting for surgery is therefore varied in age and general condition, ranging from fit young men to steroid dependent frail arthritic patients. The degree of instability and the spinal cord compression are also variable. Gauging these parameters has an important bearing on the anaesthetic management. We present management of six patients with atlanto axial subluxation in our institution. PMID- 1900545 TI - Studies on glycosylated plasma proteins in diabetic patients. AB - The level of glycosylated haemoglobin in the blood is considered as an index of long term blood glucose levels in diabetic patients. Glycosylation of structural proteins also occur. The present study describes the levels of glycosylated blood proteins (nonenzymatic) and blood glycoproteins (enzymatic glycosylation) in four groups of diabetic patients (n = 80) as well as non-diabetic control subjects (n = 20). The patients were divided according to the treatment they received. Glycosylated haemoglobin, glycosylated plasma proteins, fasting plasma glucose, hexosamine, sialic acid and mucoproteins were measured in each subject. All of these measurements were significantly increased in diabetic patients however, glycoproteins were not significantly correlated with glycosylated haemoglobin or fasting glucose. PMID- 1900546 TI - A review of 6978 consecutive admissions to the recovery room at a university hospital. AB - Recovery from anaesthesia is a time of potential danger to the surgical patients. A retrospective audit of all recovery room admissions over a period of 18 months was carried out at the Aga Khan University Hospital. During this period 6978 patients were admitted to the recovery area and 695 had one or more complications. The complications were recorded by the recovery room nursing staff in a recovery log book. The breakdown of complications according to different physiological systems is discussed. Several surveys have reviewed complications in the western population, but in contrast, no study is available in Pakistani patients. It is recommended that since one in ten patients is likely to have a problem in the early post-operative period, the local hospitals should provide adequate facilities meeting the criteria laid down for the recovery rooms in modern anaesthetic practice. PMID- 1900547 TI - Laboratory medicine. Basic principles. PMID- 1900548 TI - Etiological study of chronic osteomyelitis in Karachi. PMID- 1900549 TI - Cholecystectomy with and without drainage. AB - Thirty patients underwent cholecystectomy without drainage, and 16 matched controls cholecystectomy with drainage. The wound infection rate was lower, hospital stay shorter and overall complication rate less in undrained patients. This study suggests that surgical drainage after uncomplicated cholecystectomy is unnecessary and may be unwise. PMID- 1900550 TI - Halofantrine hydrochloride--efficacy and safety in children with acute malaria. AB - Thirty two children with symptomatic malaria due to P. vivax and P. Falciparum infections were treated with three doses of Halofantrine hydrochloride 8 mg/kg body weight every 6 hours. Mean fever clearance was 30 hours (range 24-48 hours). No significant clinical or biochemical side effects were observed. Symptoms cleared rapidly. Halofantrine hydrochloride was found to be highly effective and appeared to have no side effects in children with acute malaria infections. PMID- 1900551 TI - [The disturbance of cell membrane signal transduction system in cardiomyopathy]. PMID- 1900552 TI - OKT3 first-dose reaction: association with T cell subsets and cytokine release. AB - Use of the monoclonal antibody OKT3 to prevent or treat allograft rejection has become commonplace. Its administration is often complicated by serious side effects, usually occurring within one to two hours after OKT3 is given, and is termed first-dose reaction. The mechanism underlying these signs and symptoms is poorly defined, but may be related to cytokine release. Twenty-three kidney or kidney/pancreas transplant recipients received OKT3 as treatment of acute rejection. Signs and symptoms occurring after the first dose were observed and quantitated prospectively, and a reaction score was calculated. Blood was drawn immediately before, and at 2 and 24 hours after the first dose of OKT3 for determination of interleukin-2 (IL2), interferon-gamma (IFN gamma), and tumor necrosis factor-alpha (TNF alpha) levels, and flow cytometric analysis of T cell subsets. Two groups were defined based on severity of first-dose reaction. Group 1 patients (N = 11) had very mild reactions (reaction score less than or equal to 3); Group 2 patients (N = 12) had more severe reactions (score greater than or equal to 5). All patients demonstrated a significant rise in serum TNF alpha from baseline to two hours after OKT3 (9 +/- 3 pg/ml to 378 +/- 54 pg/ml, P less than 0.0001), and there was significant correlation between reaction scores and two hour TNF alpha levels (P = 0.005). Group 2 patients had higher TNF alpha levels at two hours than did Group 1 patients (484 +/- 75 pg/ml vs. 263 +/- 62 pg/ml, P = 0.04). Levels of IL2 and IFN gamma were not elevated at any sampling time.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1900554 TI - [Antibiotic associated recurrent diarrhea cured with fecal streptococci]. PMID- 1900553 TI - Gene expression of an endogenous retrovirus-like element during murine development and aging. AB - We have measured intracisternal A-particle (IAP) RNA levels during development and aging in C57BL/6J mouse tissues to determine possible age-dependent changes in gene expression of these retrovirus-like sequences. Total RNA was isolated from tissues of embryonic and new born mice and mice ranging in age from 2 months to 32 months of age. RNA samples were either slot-blotted directly or fractionated on denaturing agarose gels and transferred to nylon membranes. Hybridization with cloned, 32P-labeled IAP sequences showed that both the mass amounts and the relative proportions of IAP transcripts varied between tissues and as a function of age. IAP gene products were higher in brain and kidney tissues than in liver and heart tissues. The relative proportion of transcripts increased in embryonic tissues until birth and following birth, was highest in neonatal or 2-month-old tissues. The adult levels of IAP-related RNAs did not change significantly from 6 to 24 months of age. However, 32-month-old tissues exhibited the lowest content of IAP transcripts, with the exception of heart tissue which did not change with age. A 5.4-kb RNA was the predominant IAP transcript in most samples, but each tissue had a characteristic size distribution of IAP-related transcripts. These results demonstrate that transcription of IAP genes continues throughout the life span of this mouse strain with tissue-specific and age-dependent regulation of expression. PMID- 1900555 TI - [Should cost benefit analysis be done when new routines are introduced?]. PMID- 1900556 TI - Cold preservation injury of NADH-ubiquinone oxidoreductase. AB - Mitochondrial injury caused by cold preservation without oxygenation was studied polarographically. Respiration activity with glutamate as substrate was impaired after 6 hours preservation with Euro-Collin's solution at 4 degrees C, while that with succinate as substrate was maintained at the control level after 24 hours preservation. Membrane potential across mitochondrial membrane in state 4 was not damaged after 24 hours preservation. These results indicate that NADH-ubiquinone oxidoreductase is impaired during cold and simple preservation. PMID- 1900557 TI - Gastric effects of thyrotropin-releasing hormone microinjected into the dorsal vagal nucleus in cats. AB - We investigated the gastric acid secretory and motility responses to microinjection of thyrotropin-releasing hormone (TRH) into the dorsal motor nucleus of the vagus (DMV) in anesthetized cats. Gastric acid output was collected every 15 min through a gastric cannula after saline flush and titrated to pH 7.0. Antral and corpus contractions were continuously recorded by extraluminal force transducers. TRH dissolved in 200 nl of saline and microinjected unilaterally into the DMV induced a dose-dependent (50-200 ng) increase in gastric acid secretion. The acid secretory response began in the first 15 min collection and lasted 45 min. TRH frequently increased the force of contractions of the antrum and corpus within one minute of microinjection. The minimal effective dose for eliciting increased motility was lower than for inducing acid secretion. These results demonstrate that TRH acts in the DMV of cats to stimulate gastric acid secretion and contractions. PMID- 1900558 TI - Naloxone reverses L-dopa induced overstimulation effects in a Parkinson's disease animal model analogue. AB - Chronic L-DOPA treatment of Parkinson's disease frequently leads to the development of motoric overstimulation and hyperkinetic movements. To investigate this problem in the laboratory, rats surgically altered by unilateral 6 hydroxydopamine lesions (6-OHDA) were chronically treated with one L-DOPA (10 mg/kg i.p.) injection per day for 20 days. In this 6-OHDA rotation model, the unilateral dopamine denervation results in a profound contralateral sensory-motor neglect and the animals spontaneously rotate in a direction ipsilateral to the dopamine depleted hemisphere. Initially, the L-DOPA treatment did not alter the response bias but after several weeks, the response bias was reversed and the animals rotated in the formerly akinetic direction, contralaterally, at a significantly higher level. Using this overstimulation effect as an analogue of the clinically observed L-DOPA overstimulation, animals were given naloxone in conjunction with the L-DOPA treatment. Naloxone (0.10, 0.25 and 0.50 mg/kg i.p.) produced a dose related decrease in the L-DOPA induced contralateral rotation. Consistent with an expected selective effect on the L-DOPA induced rotation, a dose related increase in ipsilateral rotation was observed. These results suggest that naloxone can attenuate the overstimulation effect of L-DOPA and that this effect is not attributable to non-specific response suppression effects. PMID- 1900559 TI - Comparison of alcohol dehydrogenase expression in Drosophila melanogaster and D. simulans. AB - Alcohol dehydrogenase (ADH) gene expression was analyzed in Drosophila melanogaster and its sibling species D. simulans. The levels of ADH activity, ADH cross-reacting material (CRM), and ADH-mRNA were analyzed for several strains of each species, which derive from diverse geographic locations around the world. There is considerable quantitative variation in ADH activity, CRM level, and RNA level among strains within species at all developmental stages. However, the only consistent differences between the two species are in pupal RNA level and in late adult activity and CRM level. Late-adult melanogaster flies that are homozygous for the Slow allozyme have approximately twice the level of ADH activity and CRM as do simulans flies. The regression of activity on CRM over strains is highly significant and essentially the same for each species, which means that most, if not all, of the activity difference between the species is due to a difference in concentration of the ADH protein. In contrast, there is no significant regression of CRM level on mRNA level in adults of either species; nor is there a significant difference in RNA level between species. Therefore, the difference in ADH protein concentration is not due to RNA template availability. Thus, the interspecific difference in ADH level in adults must be due either to a difference in the rate of translation of the two RNAs or to a difference in protein stability. PMID- 1900560 TI - Basic benefits and the hope for rational rationing. PMID- 1900561 TI - Update: surveillance of outbreaks--United States, 1990. AB - Although disease outbreaks are often preventable public health problems, no uniform national system exists in the United States for surveillance of outbreaks. In 1988, CDC's Epidemiology Program Office participated with the epidemiology programs in four states (Maryland, New York, Oklahoma, and Washington) in a 5-month trial of an electronic system for the timely surveillance of outbreaks (1). This report updates the initial trial by summarizing a pilot project of surveillance of outbreaks in nine states- Maryland, Mississippi, Missouri, New York, Oklahoma, Rhode Island, South Dakota, Vermont, and Washington. PMID- 1900563 TI - Alcohol-related traffic fatalities among youth and young adults--United States, 1982-1989. AB - Unintentional injuries account for approximately half of all deaths among young persons aged 15-24 years in the United States; of these deaths, approximately 75% involve motor vehicles. Although alcohol use increases the risk for a motor vehicle crash for all drivers, for young drivers the risk begins to increase at very low blood alcohol concentrations (BACs). Moreover, in young persons who drive after drinking, the relative risk for crash involvement is greater at all BAC levels than it is for older drinking drivers. This report summarizes data from the National Highway Traffic Safety Administration's (NHTSA) Fatal Accident Reporting System on trends in alcohol-related traffic fatalities (ARTFs) in the United States from 1982 through 1989; trends are presented for three groups of young persons (15- to 17-, 18- to 20-, and 21- to 24-year-olds) and are compared with those for adults aged greater than or equal to 25 years. PMID- 1900562 TI - Update: Yersinia enterocolitica bacteremia and endotoxin shock associated with red blood cell transfusions--United States, 1991. AB - From April 1987 through August 1988, four cases of Yersinia enterocolitica bacteremia associated with red blood cell (RBC) transfusions were reported to CDC. This report summarizes findings from the investigation of an additional six cases reported from six different states from January 1989 through February 1991. PMID- 1900564 TI - Quarterly table reporting alcohol involvement in fatal motor vehicle crashes. PMID- 1900565 TI - Fatal pediatric poisoning from leaded paint--Wisconsin, 1990. AB - Although fatal lead poisoning among children occurs rarely in the United States, it represents a medical and public health emergency. This report summarizes the investigation of a child who died from poisoning associated with ingestion of lead-based paint. PMID- 1900566 TI - Characteristics of, and HIV infection among, women served by publicly funded HIV counseling and testing services--United States, 1989-1990. AB - In 1990, the number of reported acquired immunodeficiency syndrome (AIDS) cases among women in the United States exceeded 15,000, an increase of 34% from 1989 (1). Public health surveillance of the human immunodeficiency virus (HIV)/AIDS epidemic has included monitoring of publicly funded voluntary counseling and testing (CT) programs, such as the voluntary client record system (representing 43% of all reported CT visits) that collects detailed information for each CT visit. This report summarizes findings based on information from the client record system for women who received public CT services during 1989 and 1990. PMID- 1900567 TI - Tuberculosis outbreak on Standing Rock Sioux Reservation--North Dakota and South Dakota, 1987-1990. AB - From 1987 through 1988, a cluster of cases of tuberculosis (TB) occurred among persons residing on the Standing Rock Sioux Reservation; recognition of this cluster prompted an epidemiologic investigation by the Indian Health Service (IHS), Standing Rock Sioux Tribal Health and Community Health Programs, South Dakota State Department of Health, North Dakota State Department of Health, and CDC. This report summarizes the findings of that investigation and follow-up public health interventions. PMID- 1900568 TI - The nature of X-ray-induced mutations after recovery in excision repair-deficient (mus-201) Drosophila females. AB - This paper describes the genetic analysis of X-ray-induced mutations at several visible loci (yellow, white, Notch, vermilion and forked) located on the X chromosome of Drosophila melanogaster after recovery in excision repair-deficient condition (mus-201). A total of 118 mutations observed in 83636 F1 females were analyzed. The white mutations in particular have been investigated at the molecular level. The results show that: (1) the frequency of recovered whole-body mutations is similar or slightly lower in repair-deficient than in repair proficient condition (respectively 1.5 x 10(-4)/locus/15 Gy and 2.3 x 10( 4)/locus/15 Gy); (2) the frequency of observed mosaic mutations is significantly higher in the repair-deficient condition than in the proficient condition (respectively 2.7 x 10(-4)/locus/15 Gy and 0.9 x 10(-4)/locus/15 Gy); (3) the analysis of F2 male lethal mutations and the cytological analysis of the recovered mutations in the excision repair-deficient condition indicate a decrease in mutations associated with gross chromosomal aberrations (including multilocus deletions); (4) at the molecular level, the spectrum of recovered intragenic mutations is similar after excision-deficient and -proficient repair. These results indicate that excision repair is involved in X-ray-induced DNA damage that is repaired efficiently in the normal repair condition, but bypassed in the excision repair-deficient condition, leading to mosaic mutations. In addition, lesions that apparently cannot be bypassed by DNA replication lead to a decrease in the fraction of mutations due to gross chromosomal aberrations among the whole-body mutations. PMID- 1900569 TI - Synergism between aflatoxins in covalent binding to DNA and in mutagenesis in the photoactivation system. AB - Aflatoxins (AFs) produce singlet oxygen upon their exposure to UV (365-nm) light. Singlet oxygen in turn activates them to mutagens and DNA-binding species. DNA binding and mutagenesis by AFs were enhanced in D2O as compared to reactions in H2O, and a singlet oxygen scavenger inhibited mutagenesis. DNA photobinding of 3H AFB1 increased in the presence of unlabeled AFB2, and the addition of AFB2 enhanced mutagenesis by AFB1 in a synergistic manner. These results are compatible with the notion that singlet oxygen, formed by one aflatoxin molecule, can readily activate another aflatoxin molecule. This may bear an environmental implication in that the weakly carcinogenic AFB2, which is often produced in nature together with AFB1, may be important in enhancing the activation of AFB1 by sunlight. PMID- 1900570 TI - Cytogenetic characterization of the ionizing radiation-sensitive Chinese hamster mutant irs1. AB - The X-ray-sensitive mutant V79 cell line irs1 was characterized with respect to chromosomal aberrations induced by 137Cs, mitomycin C (MMC), and decarbamoyl mitomycin C (DCMMC). To measure chromosome damage induced at different cell cycle stages, irs1 and the parental V79-4 cell lines were pulse-labeled with bromodeoxyuridine (BrdUrd) at the time of exposure and harvested at various intervals corresponding to exposure in G1, S, and G2 phases of the cell cycle. Metaphase spreads were stained with an anti-BrdUrd antibody, followed by a fluorescein-conjugated second antibody. With propidium iodide as a counter stain, cells were scored for aberrations. Compared to the parental V79 cells, irs1 cells had: (1) greatly increased sensitivity to all 3 agents; (2) a high frequency of chromatid exchanges after exposure in each phase of the cell cycle; and (3) more sensitivity to the agent causing crosslinks (MMC) than its monofunctional analog (DCMMC). The finding of chromatid-type damage in cells exposed to ionizing radiation during G1 is atypical of normal cells, but is similar to observations made in several mutant rodent cell lines and in ataxia telangiectasia cells. Our results suggest that the defect in irs1 cells can manifest itself as misrepair or misreplication during all phases of the cell cycle and leads to a high incidence of chromatid exchanges and deletions. PMID- 1900571 TI - Isolation and characterization of nitrogen mustard-sensitive mutants of Chinese hamster ovary cells. AB - Three nitrogen mustard-sensitive lines of Chinese hamster ovary cells were isolated from mutagenized cultures using the procedure of Thompson et al. (1980). The lines, designated NM1, NM2 and NM3, were 2.1-, 17- and 6.8-fold more sensitive to nitrogen mustard, respectively, than their parent, wild-type, line as determined by the dose required to kill 90% of the cells, IC90. Patterns of cross-sensitivity to other DNA-damaging agents including ultraviolet light, cis diamminedichloroplatinum, and other alkylating agents were determined for each line. Analysis of these results suggests that the phenotypes of the mutant lines are different from those lines reported previously. PMID- 1900572 TI - Effect of pH on the activity and stability of clastogens in the in vitro chromosomal aberration test with Chinese hamster ovary K1 cells. AB - The effect of the pH of the medium on the clastogenic activity of several direct acting and indirect clastogens was evaluated in the in vitro chromosomal aberration test with Chinese hamster ovary K1 cells. Furthermore, the stability of the chemicals in the cell culture medium was measured by HPLC over the pH range of 5.0-11.0. The activity of the direct-acting clastogens mitomycin C (MMC), N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) and 4-nitroquinoline-1-oxide (4NQO) at various pH values depended on their stability. In the case of ENNG, its clastogenic activity decreased to about one-fifth at pH 9 but was about twice as high at acidic pH compared with that at pH 7.4. This is consistent with the observation that ENNG is unstable at basic pH; the residual content of ENNG was 0.5% of the initial amount in cell culture medium at pH 9.0 after a 2-h incubation. 4NQO was unstable at strongly basic pH (pH 10-11), and MMC was unstable at pH 5.0 and pH 11.0. The frequencies of chromosomal aberrations induced by MMC and ENNG were correspondingly decreased at these pH values. On the other hand, the clastogenicities of the indirect clastogens 7,12 dimethylbenz[a]anthracene (DMBA), benzo[a]pyrene (B(a)P) and dimethylnitrosamine (DMN), which require metabolic activation, were reduced at pH 10-11 and pH 5.8. The frequencies of chromosomal aberrations at these pHs were almost equal to negative control values. These chemicals were stable in the medium in the absence of S9 mix over the pH range of 5.0-11.0. Thus clastogenicity of indirect-acting clastogens is reduced under extreme pH conditions, probably because of the instability or nonformation of the active form. The present results indicate that the clastogenic activity of any compound will depend on its stability in the medium irrespective of its direct- or indirect-acting nature. In addition, some of the chemicals that are recognized as clastogens presumably might induce chromosomal aberrations by means of acidic pH itself. It is, therefore, important to take account of the pH of the treatment medium in evaluating the clastogenicity of chemicals. PMID- 1900573 TI - Inhibition by diacylmethane derivatives of mutagenicity in Salmonella typhimurium and tRNA-binding of chemical carcinogens. AB - Effects of diacylmethanes on the mutagenicity of 2-naphthohydroxamic acid, methylnitrosourea, benzo[a]pyrene and aflatoxin B1 in S. typhimurium and the tRNA binding by benzo[a]pyrene and aflatoxin B1 were investigated. Acetylacetone, benzoylacetone and dibenzoylmethane inhibited the mutagenicity of 2 naphthohydroxamic acid, and dibenzoylmethane and 1,3-indandione inhibited that of methylnitrosourea, benzo[a]pyrene and aflatoxin B1. The binding to tRNA of benzo[a]pyrene and aflatoxin B1 was inhibited by benzoylacetone and dibenzoylmethane, and dibenzoylmethane, 1,3-indandione and 1,1,1 trifluoroacetylacetone, respectively. The inhibition of methylnitrosourea mutagenicity was observed when the bacteria were exposed concomitantly to the inhibitors and the mutagen, but not when they were exposed to the inhibitors 1 h after exposure to the mutagen. These results demonstrate that active methylene compounds can inhibit mutagenicity and nucleic acid-binding of chemical carcinogens presumably by trapping carcinogenic electrophiles, and they are potential anti-carcinogenic agents during the initiation stage. PMID- 1900574 TI - Transforming growth factors beta 1 and alpha in chronic liver disease. Effects of interferon alfa therapy. AB - BACKGROUND: Cirrhosis is a diffuse process of hepatic fibrosis and regenerative nodule formation of unknown pathogenesis. Transforming growth factor (TGF) beta 1 induces the production of extracellular matrix proteins by liver cells and has been implicated in the pathogenesis of hepatic fibrosis in laboratory animals. TGF alpha is a hepatocyte mitogen that participates in liver regeneration. METHODS: Using Northern blot analysis, we studied the expression of TGF beta 1 messenger RNA (mRNA) in liver specimens from 42 patients with chronic hepatitis and cirrhosis and 12 subjects with either normal or fatty livers. The results were correlated with measurements of procollagen Type I mRNA in liver tissue, procollagen Type III peptide in serum, and the degree of histologic injury. We also investigated whether TGF alpha mRNA would be detectable in biopsy specimens of livers with proliferative activity. RESULTS: TGF beta 1 mRNA expression correlated closely with the expression of procollagen Type I mRNA (r = 0.94) and serum procollagen Type III peptide (r = 0.89) and with the histologic activity index (r = 0.73). All patients with increased fibrogenic activity (serum procollagen Type III peptide level, greater than 11.9 micrograms per liter) had increased levels of TGF beta 1 mRNA (2 to 14 times the levels in the control group or in patients with normal fibrogenic activity), and both TGF alpha and H3 histone (a marker of DNA synthesis) mRNAs were detectable in patients with regenerative nodules. Six of eight patients with hepatitis C treated with interferon alfa for one year had sustained clinical responses with normalization of serum procollagen Type III peptide and aminotransferase activity. All these patients had normal levels of TGF beta 1 mRNA in liver specimens obtained at the end of the year. CONCLUSIONS: TGF beta 1 may have an important role in the pathogenesis of fibrosis in patients with chronic liver disease, and TGF alpha expression may be associated with liver regeneration in these patients. PMID- 1900575 TI - Administration of thyroxine in treated Graves' disease. Effects on the level of antibodies to thyroid-stimulating hormone receptors and on the risk of recurrence of hyperthyroidism. AB - BACKGROUND: Antibodies to thyroid-stimulating hormone (TSH) receptors that stimulate the thyroid gland cause hyperthyroidism in patients with Graves' disease, and their production during antithyroid drug treatment is an important determinant of the course of the disease. One factor that might contribute to the persistent production of antibodies to TSH receptors is stimulation of the release of thyroid antigens by TSH during antithyroid drug therapy. We therefore studied the effect of the suppression of TSH secretion by thyroxine on the levels of antibodies to TSH receptors after thyroid hormone secretion had been normalized by methimazole. METHODS AND RESULTS: The levels of antibodies to TSH receptors were measured during treatment with methimazole, either alone or in combination with thyroxine, in 109 patients with hyperthyroidism due to Graves' disease. The patients first received 30 mg of methimazole daily for six months. All were euthyroid after six months, and their mean (+/- SD) level of antibodies to TSH receptors decreased from 64 +/- 9 percent to 25 +/- 15 percent (P less than 0.01; normal, 2.9 +/- 1.4 percent). Sixty patients then received 100 micrograms of thyroxine and 10 mg of methimazole and 49 received placebo and 10 mg of methimazole daily for one year. In the thyroxine-treated group, the mean serum thyroxine concentration increased from 108 +/- 16 nmol per liter to 145 +/- 11 nmol per liter (P less than 0.01), and the level of antibodies to TSH receptors decreased from 28 +/- 10 percent to 10 +/- 3 percent after one month of combination therapy. In the patients who received placebo and methimazole, the mean serum thyroxine concentration decreased and the level of antibodies to TSH receptors did not change. Methimazole, but not thyroxine or placebo, was discontinued in each group 1 1/2 years after the beginning of treatment. The level of antibodies to TSH receptors further decreased (from 6.6 +/- 3.2 percent at the time methimazole was discontinued to 2.1 +/- 1.2 percent one year later) in the patients who continued to receive thyroxine, but it increased (from 9.1 +/ 4.8 percent to 17.3 +/- 5.8 percent during the same period) in the patients who received placebo. One patient in the thyroxine-treated group (1.7 percent) and 17 patients in the placebo group (34.7 percent) had recurrences of hyperthyroidism within three years after the discontinuation of methimazole. CONCLUSIONS: The administration of thyroxine during antithyroid drug treatment decreases both the production of antibodies to TSH receptors and the frequency of recurrence of hyperthyroidism. PMID- 1900577 TI - Penicillin resistance in Neisseria meningitidis. PMID- 1900576 TI - High titers of cytopathic virus in plasma of patients with symptomatic primary HIV-1 infection. AB - BACKGROUND: Primary infection with the human immunodeficiency virus (HIV-1) frequently causes an acute, self-limited viral syndrome. To examine the relations among viral replication, the immune response of the host, and clinical illness during this initial phase of infection, we undertook a quantitative, molecular, and biologic analysis of infectious HIV-1 in the blood and plasma of three patients with symptomatic primary infection and of a sexual partner of one of them. METHODS: During an eight-week period of primary infection, HIV-1 was cultured frequently in dilutions of plasma and peripheral-blood mononuclear cells (PBMC), and levels of HIV-1 antigen and antibody were determined sequentially by enzyme-linked immunosorbent assay and immunoblotting. Replication-competent HIV-1 proviruses were cloned and characterized biologically. RESULTS: Six to 15 days after the onset of symptoms, high titers of infectious HIV-1 (from 10 to 10(3) tissue-culture-infective doses per milliliter of plasma) and viral p24 antigen were detected in the plasma of all three patients. These titers fell precipitously by day 27, and the decline coincided with an increase in the levels of antiviral antibodies and the resolution of symptoms. Sequential isolates of virus from plasma and PBMC obtained throughout the period of primary infection, as well as virus derived from two molecular proviral clones, were highly cytopathic for normal-donor PBMC and immortalized T cells, despite the marked reduction in the titers of virus in plasma. CONCLUSIONS: Primary, symptomatic HIV 1 infection is associated with high titers of cytopathic, replication-competent viral strains, and during such infection potential infectivity is enhanced. Effective control of HIV-1 replication during primary infection implies the activation of clinically important mechanisms of immune defense that merit further examination in relation to the development of antiviral therapy and vaccines. PMID- 1900578 TI - Nitroglycerin to treat acute loss of vision. PMID- 1900579 TI - [Infections in dialysis patients]. PMID- 1900580 TI - [Development of a serological test for tuberculosis]. AB - Antigens secreted by M. tuberculosis in the culture medium and antigens obtained from sonicated M. tuberculosis were characterized, at the laboratory of Tropical Hygiene of the Royal Tropical Institute and the division of Pulmonary Medicine at the Academic Medical Centre, in order to explore which antigens could be valuable in the development of a serological test for tuberculosis. Using murine monoclonal antibodies in immunoblot, a pattern of protein bands distinct from that of the corresponding M. tuberculosis sonicate was found in the culture medium. The major protein bands of the culture medium, of 24 and 12 kD, and the major protein band of 16 kD in sonicate were purified. These antigens were tested in ELISA with sera from 20 patients with tuberculosis, diagnosed by a positive culture of M. tuberculosis, and from 21 control subjects. The ELISA results obtained with these 3 antigens were combined and the mean value obtained in the control group plus 2 times the standard deviation was chosen as the cut-off level. Sixteen of the 20 patients with tuberculosis had antibodies against 1 of the purified antigens, while none of the control subjects had. By combining the results, obtained with these 3 antigens, 17 of the 20 patients with tuberculosis were positive in this serological test and none of the control subjects. The 24, 12 and 16 kD antigens may be valuable for the development of a serological test for tuberculosis. PMID- 1900581 TI - [In-vitro fertilization in The Netherlands]. PMID- 1900582 TI - [Current viewpoints in the diagnosis and treatment of acidosis in resuscitation]. PMID- 1900583 TI - Importance of physical and laboratory examination on patients with mental disturbances. PMID- 1900584 TI - Positive and negative health behaviors used to ensure compliance with the U.S. Army's weight control standards by a reserve component unit. PMID- 1900585 TI - Cyproheptadine for combat nightmares in post-traumatic stress disorder and dream anxiety disorder. AB - Pharmacologic treatment of patients with post-traumatic stress disorder often involves antidepressant drugs. Combat nightmares often persist. The addition of cyproheptadine, in a median dose of 16-24 mg orally at night, controls the nightmares. PMID- 1900586 TI - Stress management in a military health promotion program: effectiveness and cost efficiency. AB - An experimental study was conducted to determine the impact of a stress management course within a health promotion program. Assessments were made of stress related symptoms, perception of stress, and blood pressure. Costs of the program per benefit were calculated. PMID- 1900587 TI - The establishment and validation of the mobile immunization team concept at a clinic level. AB - Faced with unacceptably low and declining overall immunization compliance, as well as specific flu immunization compliance, the Executive Committee of a 32 person Air National Guard clinic asked the nursing service to devise a method of correcting these deficiencies as rapidly as possible and maintaining immunization compliance at a rate of 90% or better of the total patient population of approximately 1,100 full-time and Guard personnel for whom the clinic was responsible. The concept of a mobile immunization team was devised and validated over a 2-year interval. In order to successfully develop and implement this concept, command emphasis and a high level of cooperation from both clinic personnel and the Unit Commanders involved was requested and received. The make up of the team, risk management, the timing and place of team visits, and record keeping were among the problems addressed and resolved. The mobile immunization team concept was a success, achieving excellent overall immunization compliance and outstanding compliance with the flu immunization program over a 2-year period. PMID- 1900588 TI - Fetal macrosomia in a military hospital: incidence, risk factors, and outcome. AB - The purpose of this paper is to determine the incidence of fetal macrosomia, analyze risk factors, and review maternal and fetal outcome. Macrosomia occurred in 15.1% of deliveries, with very macrosomic fetuses comprising 4.1% of these pregnancies; 61.3% were male. Diabetes mellitus, post-term pregnancy, and excessive weight gain were identified as maternal risk factors. The incidence of shoulder dystocia, birth injury, and low Apgar scores was significantly higher than in controls. In addition, cesarean section rates were higher for the macrosomic groups. Fetuses delivered vaginally had more frequent birth injury than those delivered by cesarean section. Women at risk for fetal macrosomia should be screened, and liberal use of cesarean section is recommended. PMID- 1900589 TI - Professional nurse information day: a recruitment strategy for registered nurses. AB - The shortage of and demand for professional registered nurses is growing at an ever-increasing rate. Military facilities must consider alternative strategies for recruiting these professionals into their staffs even in the midst of worsening budget and personnel constraints. One idea is reported here that proved successful for a medical center overseas with no money expenditure. Recommendations for repetitions of a similar program are included. PMID- 1900590 TI - Descriptive analysis of diagnosis-related groups in patients from a Veterans Administration Medical Center. AB - Discharge diagnoses from October 1, 1987 to September 30, 1988 were analyzed to quantitate infection. Four hundred forty-nine (4.8%) of 9,290 discharges (excluding 1-day stays) were infections. Pneumonia, caused by all etiological agents, was responsible for 2.4% of the principal diagnoses. These data help define the role of infection in hospitalized veterans and further supports earlier findings that respiratory tract infections are the most common of all infections in our veterans. PMID- 1900591 TI - Combat stress reaction and changes in military medical profile. AB - This study examines changes in the military medical profile following participation in war. Two groups of Israeli soldiers who participated in the 1982 Lebanon War were studied: 360 soldiers who were treated for immediate combat stress disorder during the war, and a matched control group of 310 soldiers who participated in the same war and were not identified as combat stress reaction casualties. Significant lowering of the profile after the war was noted for both groups. These changes were much stronger for combat stress reaction casualties. The differences between the groups were especially pronounced with regard to the addition of the psychiatric impairment category to the military medical profile. No background characteristics differentiated between combat stress reaction casualties who lowered their profile and those who did not. The implications of the findings for further research and for military mental health policy are discussed. PMID- 1900592 TI - Morbidity and mortality in U.S. Navy personnel from exposures to hazardous materials, 1974-85. AB - A total of 1,371 hospitalizations and 136 deaths occurred in U.S. Navy enlisted personnel from 1974 to 1985 as a result of exposures to hazardous materials. Exposures to various gas fumes and vapors accounted for the largest percentage of all hospitalizations (38%), and the second largest percentage of deaths (20.6%). The most frequent cause of death was from carbon monoxide poisoning; nearly 74% of all reported deaths were attributed to this gas. Hospitalization rates were highest among the 17- to 19-year-olds across all race categories. This may be attributed either to their lack of experience and knowledge concerning the safe handling of these materials, or perhaps a disproportionate number of 17- to 19 year-olds are given tasks which put them at higher risk. The Navy occupations showing the highest risk for various exposures to hazardous materials were Utilitiesman, Hull Maintenance Technician, and Boatswain's Mate. It is the inhalation of these compounds which poses the greatest health risk to personnel both onshore and aboard ships. PMID- 1900593 TI - Clinical and laboratory predictors of bacterial diarrhea in a tropical environment. AB - A total of 180 patients with diarrhea, 6 years and below, were seen and evaluated in our pediatric clinic during the months of July to December, 1986. A bacterial pathogen was isolated from the stools in 24/180 (13%). The best historical factors for predictive accuracies were abrupt onset, no vomiting before the onset of diarrhea, and greater than four stools per 24 hours. The presence of fecal leukocytes was the best screening tool for stool culture positivity. The patients identified with the above three historical factors and positive for fecal leukocytes had an 83% probability of having a positive bacterial stool culture compared to only a 5% probability if any one of the factors was absent. We were able to identify a subpopulation of American dependents in a tropical environment with diarrhea who had a high probability of having a bacterial stool pathogen based on historical factors and the fecal leukocyte test. PMID- 1900594 TI - Profiling overweight patients in the U.S. Navy: health conditions and costs. AB - The U.S.A. has the distinction of being the "fattest" nation in the world, with an estimated 34 million obese citizens. Of grave concern is the reported finding that obesity contributes to 20% of the annual mortality rate, primarily for such conditions as diabetes mellitus, digestive diseases, coronary heart disease, and cerebrovascular disease. In 1982, the Navy initiated the "Health and Physical Readiness Program" in order to establish body fat percentages and physical conditioning standards and to provide Navy personnel with weight reduction and other health promotion programs. Participation in such programs is expected to help overweight personnel solve their weight problems and reduce the risks of obesity-related conditions. The purpose of this study was (1) to identify the health conditions recorded in a sample of U.S. Navy enlisted men who had been diagnosed as obese during one or more of their admissions to a Naval hospital from 1974 through 1984, (2) to determine whether these disorders correspond with those reported in the scientific literature, and (3) to examine the obesity related costs in terms of numbers of days hospitalized and career outcome. The patient population consisted of 518 U.S. Navy enlisted men who were given a primary diagnosis of obesity and 1,092 who received a secondary or additional diagnosis of obesity on at least one of their inpatient medical records between 1974 and 1984. A 10% sample of Navy male patients, all of whom had not been diagnosed as obese, was selected as a comparison group (n = 30,829). All diagnoses (ICD-9) for each hospitalization were included in the data compilations; however, each unique diagnosis was only counted once.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1900596 TI - Staff perceptions of their work environment before and six months after an organizational change. AB - The Insel and Moos' Work Environment Scale (WES) was used to assess the impact that an organizational change would have on the nursing staff perceptions of the work environment. A comparison of before and after the supervisory change indicated that middle management supervisors have little influence on the work environment, since there was essentially no change in any of the WES scales. The working environment showed little cohesion among staff members, the focus on autonomy and self-sufficiency was average, but there was strong pressure to keep up with the never-ending work load, the staff perceived the setting as poorly organized and inefficient, they were unclear as to expectations about rules and procedures, and there was a high degree of control over the workers. An organizational change may not be the answer to the problems if the problems have more to do with the corporate philosophy. It may be time to look at mechanisms that create working environments in which employees actually feel their work is an important contribution to the organization. PMID- 1900595 TI - Unplanned pregnancy among active-duty Army females as a readiness issue. AB - Unplanned pregnancy creates significant problems for active-duty female soldiers and also elicits concern among military leaders when planning for mobilization. The purpose of this three-group comparative survey is to ascertain probable reasons for unplanned pregnancy occurrence that will be useful in developing appropriate interventions directed at decreasing the incidence of such pregnancies. Active-duty female soldiers (n = 112) in-processing at a large military installation responded to a 41-item questionnaire focused on respondents' reproductive histories, beliefs and knowledge about contraception, and contraceptive use. Descriptive statistics, the Kruskal-Wallis One-Way Analysis of Variance, and Chi-Square non-parametric statistical tests were used for analysis of the data. Findings revealed that when compared to the two post adolescent groups, the adolescent female soldiers reported: (a) a greater number of sexual partners, (b) greater frequency of intercourse, (c) less knowledge about the reproductive cycle, and (d) greater non-use of any birth control method. PMID- 1900597 TI - A retrospective analysis of diseases associated with indeterminate HIV western blot patterns. AB - Some individuals possess antibodies which react to HIV-1 Western blot proteins in patterns not diagnostic for HIV infection. A retrospective chart review of patients exhibiting such indeterminate HIV Western blots was performed in comparison to a control cohort of sex- and age-matched individuals from the same population of HIV-negative blots to determine if such blots were associated with any specific disease states. Twenty such patients with 25 indeterminate blots among them were found in a total population of 816 (2.5%). GAG-only (core) Western blots comprised the majority 84% (21/25). An indeterminate blot was statistically associated with Hashimoto's thyroiditis (p less than 0.01) and non Hodgkin's lymphoma (p less than 0.05). Kikuchi's disease and malignant histiocytosis were associated but the numbers were too small to reach statistical significance. The possibility that these diseases are caused by novel retroviruses, cross-reactive with HIV-1, is discussed in lieu of these findings. PMID- 1900598 TI - The United States Army Special Forces--Walter Reed Army Institute of Research Field Epidemiological Survey Team (Airborne), 1965-1968. AB - In 1965, an innovative concept in field medicine was launched in the form of a team of highly-trained, multi-disciplined AM-EDD specialists who were assigned to the Walter Reed Army Institute of Research and attached to the 5th Special Forces Group (Abn) while in Vietnam. Officially designated the U.S. Army Special Forces- Walter Reed Army Institute of Research Field Epidemiologic Survey Team (Airborne) (WRAIR-FEST), these personnel took their investigative skills into some of the more remote areas of Vietnam to study disease transmission in militarily hostile circumstances. From 1966-1968, numerous important studies of arthropod-borne diseases, including malaria, scrub typhus, and plague, and of gastrointestinal disorders, medically important arthropods, and cutaneous diseases were successfully conducted. PMID- 1900599 TI - Managing acute complications of diabetes. PMID- 1900600 TI - Nursing case management: critical pathways to desirable outcomes. PMID- 1900601 TI - The effect of intrauterine intravascular blood transfusion on iron metabolism in fetuses with Rh alloimmunization. AB - Fetal plasma ferritin concentrations were measured in 43 normal fetuses at 18-36 weeks and in 78 blood samples collected before transfusion from 23 fetuses with Rh alloimmunization. Among controls, there was a significant correlation between fetal serum ferritin and gestational age (r = 0.39, P = .009), consistent with an increase in fetal storage of iron during normal pregnancy. In Rh-alloimmunized fetuses, the ferritin concentration was above the reference range in 63% of the samples. Before the first transfusion, the fetal ferritin concentration was increased compared with controls (mean multiples of the mean = 2.6, range 1-26) and showed a negative correlation with fetal hematocrit (r = -0.43, P less than .05), suggesting that the worse the fetal anemia, the higher the iron store. Serial transfusions were associated with further increase in serum ferritin, which correlated primarily with the total volume of blood transfused. Three fetuses had plasma serum ferritin concentrations above 1 mg/L, a level compatible with a diagnosis of iron overload in children. These observations suggest that there is a potential risk of iron overload in Rh-alloimmunized fetuses undergoing intrauterine blood transfusion. PMID- 1900602 TI - The efficacy of chlorhexidine gel in reduction of Streptococcus mutans and Lactobacillus species in patients treated with radiation therapy. AB - Xerostomia may develop in patients with cancer who receive radiotherapy that includes the salivary glands in the field. These patients are at high risk of rampant dental caries. Streptococcus mutans and Lactobacillus species have been associated with dental caries. Quantitative counts of these organisms demonstrated high caries risk due to streptococci in 66% and due to lactobacilli in 100% of patients studied. Use of chlorhexidine rinse was shown to reduce S. mutans counts 1.1 logs and lactobacilli 1.1 logs. The use of chlorhexidine gel resulted in a reduction of S. mutans 1.2 logs and lactobacilli 2.2 logs. In the subjects using the rinse, caries risk due to streptococci was reduced to low levels in 44% and due to lactobacilli in only one subject, with reduction to moderate risk in one third and no change in risk in the remaining patients. The use of chlorhexidine gel was found to reduce the caries risk associated with streptococci to low levels in all patients, and the risk associated with lactobacilli to low and moderate risk in two thirds of patients. PMID- 1900604 TI - History of the American Neurotology Society (1965-1990). PMID- 1900603 TI - Radiographic evaluation of intraosseous implants of endodontic materials. AB - Following several case reports of cyst development after endodontic treatment of decidous teeth, the osseous response to formaldehyde- or phenol-based materials was evaluated by a standardized radiographic technique. Endodontic medicaments contained in Teflon carriers were implanted between feline deciduous canine and molar teeth and the permanent successional teeth. Persistent radiolucency surrounding formocresol implants and sequestration of Kri-paste implants were noted in contrast to apparent bony healing around the zinc oxide-eugenol controls and those implants containing glutaraldehyde. These results suggest a greater tissue tolerance to glutaraldehyde-containing agents in contrast to the more traditional endodontic agents used in deciduous teeth. PMID- 1900605 TI - Modified Rambo meatoplasty in translabyrinthine tumor removal. AB - Spinal fluid otorrhea and otorhinorrhea are morbid complications that occur in up to 18% of patients after removal of translabyrinthine tumor. Both of these problems can be significantly reduced if, during the initial surgery, the posterior canal wall is taken down and the tympanic membrane and external auditory canal skin are removed for better exposure of the eustachian tube orifice. The external auditory meatus can then be sealed by a previously described modification of the Rambo procedure. This additional procedure adds about 20 minutes to the surgery and presents a small risk of retained squamous epithelium. Fifty consecutive patients were divided into two equal groups and studied retrospectively. In group I, the patients underwent a modified Rambo meatoplasty at the time of the removal of their translabyrinthine tumor, whereas patients in group II had the tympanic orifice of their eustachian tube obstructed through the facial recess. Review of the postoperative course of these fifty patients indicated that the addition of the modified Rambo meatoplasty was justified by the overall reduction in morbidity and expense it provided. PMID- 1900606 TI - Vestibular autorotation test asymmetry analysis of acoustic neuromas. AB - The vestibular autorotation test (VAT) measures the vestibulo-ocular reflex (VOR) response from 2 to 6 Hz, during 18 seconds of active head movements, while the patient attempts to fixate on a wall-mounted target. A new method of measuring eye velocity asymmetry from VAT data is presented, based on computer estimation of the 0th harmonics of discrete Fourier spectra over short segments of digital eye and head velocity records. Eye asymmetries greater than a 3% normal range are shown to be directionally correlated with the side of the lesions in patients with unilateral labyrinthectomies. Among patients with a diagnosis of acoustic neuroma, who were tested preoperatively with the VAT, nine of nine patients showed eye asymmetries greater than 3% toward the side of the neuroma. Those patients with acoustic neuromas who have sufficiently vigorous high-frequency head responses showed mean percentages of eye asymmetry that were linearly correlated with the size of the acoustic neuroma. These results suggest that VAT high-frequency asymmetry provides a useful method of diagnostic evaluation of the side and extent of unilateral peripheral lesions. PMID- 1900607 TI - Intratemporal facial nerve hemangiomas. AB - Facial nerve hemangiomas are benign vascular tumors that arise within the temporal bone and have a histologic appearance similar to both cavernous hemangiomas and vascular malformations. In contrast to facial nerve schwannomas, these are extraneural tumors that cause symptoms by compression and tend to produce deficits when very small in size. We report our experience at the House Ear Clinic with 34 patients having these nonglomus intratemporal vascular tumors. Hemangiomas arising in the internal auditory canal tend to produce a progressive sensorineural hearing loss and are demonstrated with magnetic resonance imaging (MRI), whereas those at the geniculate ganglion are usually first seen with facial nerve symptoms and may require high-resolution computerized tomography (CT) for detection. Facial electromyography is helpful in establishing the diagnosis. Because of their extraneural nature, early diagnosis can permit removal of the tumor with preservation of facial nerves in some patients. PMID- 1900609 TI - Acoustic neuroma surgery: predictive criteria for hearing preservation. PMID- 1900608 TI - The "plateau effect" of cis-platinum-induced hearing loss. AB - Cis-platinum-induced hearing loss has been reported to exhibit a "plateau effect" over the 2 to 8 kHz range. We examined serial audiometry data from 27 patients treated with cis-platinum. Although a plateau at 60 to 70 dB HL often occurred, this hearing loss was clearly exceeded in a number of patients. We identified 14 patients with sufficient cis-platinum-induced sensorineural hearing loss to evaluate a plateau limit to hearing loss over the 4 to 8 kHz range. Half of these 14 patients had hearing losses that exceeded the plateau level. More severe 4 to 8 kHz hearing losses did not correlate with number of treatments, cumulative dosages of cis-platinum, pre-existing hearing loss, radiation therapy, other chemotherapeutic agents, or even hearing losses below 4 kHz. Although cis platinum therapy can induce a plateau of moderate hearing impairment for some patients over the 4 to 8 kHz range, a significant proportion of patients will experience more severe hearing impairment in this range, even after only one or two courses of cis-platinum. PMID- 1900610 TI - Tumors of the jugular foramen: surgical preservation of neural function. PMID- 1900611 TI - The trans-sigmoid, retrolabyrinthine, transtentorial approach to the brainstem. PMID- 1900612 TI - Malignant paragangliomas of the head and neck: clinical and immunohistochemical characterization. PMID- 1900613 TI - Adenomas of the mastoid and middle ear. PMID- 1900614 TI - Vestibular and postural findings in the motion sickness syndrome. AB - The motion sickness syndrome constitutes varying degrees of subjective motion intolerance and three objective findings: hyperactive VOR (79%), hip sway strategy (60%), and positional nystagmus (42%). It is present in subjects who have a strong history of motion sickness. Vestibular rehabilitation appears to help control symptoms. The study also suggests an inheritance pattern, but a structured pedigree could not be constructed. Prospective studies are warranted to further establish the patterns of the motion sickness syndrome. PMID- 1900615 TI - Vestibular function testing: an evaluation of current techniques. PMID- 1900616 TI - Auditory and vestibular function after vestibular neurectomy. PMID- 1900617 TI - Vestibular compensation after labyrinthectomy and vestibular neurectomy in cats. AB - Labyrinthectomy and vestibular neurectomy are two ablative procedures used for definitive control of disabling vertigo. It is not known if vestibular compensation after labyrinthectomy and vestibular neurectomy differs. We have addressed this question by examining the pattern of recovery of the vestibular ocular reflex in cats after either labyrinthectomy or vestibular neurectomy. Temporal bone histologic examination confirmed the surgical lesion. Our results demonstrate a reduction of the long time constant of the vestibular ocular reflex in both groups of animals. Although gain of the vestibular ocular reflex recovered substantially, it never returned to control levels in either group. In general, animals that had undergone vestibular neurectomy demonstrated greater vestibular ocular reflex asymmetries than did labyrinthectomized animals. The recovery pattern of the vestibular ocular reflex indicates vestibular compensation is more rapid after labyrinthectomy than after vestibular neurectomy. We believe this result is related to survival of the vestibular nerve after labyrinthectomy, but not after vestibular neurectomy, suggesting that the vestibular nerve can contribute to the adaptive response after labyrinthectomy. PMID- 1900618 TI - Middle fossa and intratemporal facial nerve neuromas. PMID- 1900619 TI - A temporal bone study method to evaluate clinical diagnostic criteria: permeability of patencies of the fissula ante fenestram. PMID- 1900620 TI - Techniques of and reconstruction after temporal bone resection. PMID- 1900621 TI - Secondary endolymphatic hydrops--tinnitus. PMID- 1900622 TI - Speech perception skills of children implanted with multi-channel cochlear devices. PMID- 1900623 TI - Performance of children with multichannel cochlear implants: a three-center study. PMID- 1900624 TI - Electromagnetic semi-implantable hearing device: an update. PMID- 1900625 TI - Intrinsic vasculature of the labyrinthine segment of the facial nerve- implications for site of lesion in Bell's palsy. AB - Recent studies of the intrinsic vasculature of the cat facial nerve have demonstrated relatively poor blood supply to the labyrinthine segment. In this study, the intrinsic vasculature of the human facial nerve was systematically evaluated in 25 temporal bones and three fresh cadaver nerves. Cross-sectional vessel counts were obtained for the labyrinthine, tympanic, and mastoid segments. Capillary densities for each segment were derived from these data. The labyrinthine segment of the human facial nerve, like that in the cat, contains fewer and smaller intrinsic blood vessels than do the mastoid and tympanic segments. This may indicate that the labyrinthine segment of the facial nerve may be more vulnerable to ischemic damage. In conjunction with the previously demonstrated narrowness of the labyrinthine fallopian canal, these findings support the contention that the labyrinthine segment is a likely site of lesion in Bell's palsy. PMID- 1900626 TI - Transcanal infracochlear approach to the petrous apex. AB - Computerized tomography and magnetic resonance imaging have now made it possible to reliably differentiate cholesteatoma from cholesterol granuloma of the petrous apex. The treatment for cholesteatoma is complete surgical excision when possible, whereas cholesterol granuloma needs only adequate drainage for control. A new transcanal infracochlear approach for drainage of cholesterol granuloma involving the anterior petrous apex is described. Absolute measurements from 10 cadaveric temporal bones were obtained to determine the distances between the cochlea, jugular bulb, carotid artery, and facial nerve. In all specimens the petrous apex was entered without invading the cochlea, carotid, or jugular bulb. Advantages of this technique include a more direct route to the petrous apex, dependent drainage, and preservation of the normal hearing mechanism, including the tympanic membrane. Clinical indications for this technique include failure of other treatment approaches and a high jugular bulb obstructing an infralabyrinthine approach. Experience to date shows that patients experience little difficulty from the procedure. PMID- 1900627 TI - The modified transcochlear approach to the cerebellopontine angle. AB - We have modified the transcochlear approach to improve exposure of the anterior petrous apex, clivus, anterior cerebellopontine angle, and the prepontine region. These changes include resection of the external auditory canal, middle ear, glenoid fossa, and posterior zygomatic arch. This approach provides improved exposure of the petrous carotid artery, jugular bulb, and clivus. It offers the largest and most lateral access to the anterior cerebellopontine and prepontine region. The results of this approach in 11 patients are discussed. PMID- 1900628 TI - Comparison of speech perception abilities in deaf children with hearing aids or cochlear implants. AB - The speech perception abilities of deaf children with a single- or multi-channel cochlear implant are compared with those of deaf children who derive substantial benefit from conventional hearing aids. The children with hearing aids have unaided pure-tone thresholds ranging from 90- to 110-dB HL through at least 2000 Hz, and aided thresholds of 30- to 60-dB HL. The group data show that the speech perception scores of the subjects with hearing aids were significantly higher than those of the subjects with implants on a range of speech perception measures. Although a few subjects with implants achieved scores as high as those who used hearing aids, the majority did not. Even though the children with implants receive substantial benefit from their devices, they continue to have limited auditory perception abilities relative to their peers who derive benefit from conventional hearing aids. The data highlight the importance of establishing hearing aid benefit in potential candidates for implant. PMID- 1900629 TI - MRI of the facial nerve during paralysis. AB - Gadolinium-enhanced MRI was used to evaluate 10 patients with Bell's palsy and one patient with facial paralysis secondary to Lyme disease. Nine of the eleven patients showed increased signal intensity of their facial nerve with gadolinium enhanced MRI. In all nine patients, the facial nerve was involved at the labyrinthine, geniculate ganglion and proximal tympanic portions of the facial nerve, while two of the nine patients also had involvement of the mastoid segment of the facial nerve. Patients whose facial nerve enhancement was limited to the labyrinthine, geniculate ganglion and proximal tympanic facial nerve ultimately had complete return of facial function. Patients whose facial nerve enhanced in the mastoid segment experienced incomplete return of facial function. Gadolinium is effective in localizing the site of inflammation during facial paralysis. Those patients with enhancement localized to the labyrinthine, geniculate ganglion and proximal tympanic segments were more likely to regain complete facial function. In contrast, patients who had enhancement of the mastoid segment of the facial nerve had poorer prognoses for complete return of facial function. PMID- 1900630 TI - Posterior semicircular canal occlusion in the normal hearing ear. AB - This report outlines our experience with posterior semicircular canal occlusion, a new operative procedure for intractable benign paroxysmal positional vertigo (BPPV). We postulate that the resulting solid canal "plug" prevents endolymph movement within the posterior canal, which effectively fixes the cupula. This selectively abolishes the receptivity of the posterior canal to both angular acceleration and gravity without influencing the other inner ear receptors. We previously reported the success of this procedure in two patients with BPPV and a co-existing profound sensorineural hearing loss in the affected ear. Since that report, a slightly modified technique has been used to occlude six more posterior canals--five in normal hearing ears. While our follow-up times range from only 3 to 18 months, all eight patients continue to be relieved of their BPPV. Temporary mixed hearing losses occurred in three of the five ears with normal preoperative hearing. Hearing in all five patients ultimately returned to the preoperative state. We believe this procedure is a simpler and safer alternative to singular neurectomy for the treatment of intractable benign paroxysmal positional vertigo. PMID- 1900631 TI - Management of temporal bone carcinomas: a therapeutic analysis of two groups of patients and long-term followup. AB - Fifty-one patients with squamous cell carcinomas arising within the temporal bone were subdivided into two groups. The initial group of 17 patients, seen between 1960 and 1980, were reviewed retrospectively and staged into four subgroups on the basis of initial tumor presentation and location (i.e., external auditory canal, superficial invasion, deep invasion, and tumors beyond the temporal bone). After treatment in a variety of surgical and radiotherapeutic combinations, the 5 year cure rates were: 70%, 70%, 50%, and 9%, respectively. Thirty-four patients, seen between 1980 and 1989, were placed in a new prospective protocol for combined surgery and postoperative irradiation. These patients were subdivided into the same subgroups on the basis of tumor location. The surgical procedures were formalized to be more encompassing (i.e., external canal tumors were treated by sleeve resection of the internal auditory canal and tympanic membrane, superficial invasion by superficial temporal bone resection, deep tumors by radical temporal bone resection, and those beyond the temporal bone by an infratemporal fossa approach). Radical neck dissections were performed where needed. The irradiation dosage was increased to 6250+ cGy, with a 4:1 ratio in favor of electrons for deeper penetration, and the fields were widened. At 36.6 month average followup, the cure rates were: 100%, 100%, 70%, and 65%, respectively. Six of ten patients with neck metastases at presentation had tumor recurrence or distant disease (60%). PMID- 1900632 TI - Cochlear nucleus cell size is regulated by auditory nerve electrical activity. AB - Accumulating evidence suggests that sensorineural hearing loss in animals is rapidly followed by degenerative changes in central auditory neurons. For example, cochlear removal in birds and mammals results in a reduction in central auditory neuron cell size within 48 hours. A similar decrease in cell size after pharmacologic blockade of auditory nerve electrical activity with tetrodotoxin has been reported. In the present study, we evaluate the reversibility of central auditory changes after a profound sensorineural hearing loss caused by blockade of auditory nerve actions potentials. Tetrodotoxin, which blocks voltage sensitive sodium channels, was embedded in a slow-release vehicle and placed next to the round window membrane of gerbils. Tetrodotoxin diffused into perilymph and unilaterally blocked electrical activity in auditory nerve axons. Electrical activity blockade was confirmed with recordings of auditory brainstem response. Animals were killed immediately after 24 hours of electrical blockade or 7 days after a transient 24- or 48-hour blockade. Large spherical cells of the anteroventral cochlear nucleus ipsilateral to manipulation were measured and compared to large spherical cells on the opposite, unmanipulated side of the brain. Animals killed immediately after a 24-hour blockade of electrical activity showed a mean decrease of 16% in cell size ipsilateral to the blockade (p less than 0.05). In animals allowed to recover for 7 days after blockade for 24 or 48 hours, cell size returned to previous levels. There was no longer a consistent difference in cell size between the two sides of the brain in these animals (p greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1900633 TI - Bilateral vestibular paresis: diagnosis and treatment. AB - Patients with bilateral peripheral vestibular dysfunction present a substantial diagnostic and therapeutic challenge to the otologist. Caloric irrigations that suggest bilateral weakness may mislead the clinician when considerable peripheral function remains. Rotary chair testing at several frequencies is helpful in confirming the degree of residual function and may identify patients who have a better prognosis in rehabilitation. Forty-nine patients with bilateral vestibular paresis were evaluated. The diagnosis was based on caloric responses of less than 5 degrees/sec in both ears and reduced gain on rotary chair trials. Oscillopsia occurred in the minority of patients (35%) and was rare unless severe paresis was present. Episodic vertigo occurred in 43%. All patients had abnormal posturography results, with vestibular dysfunction and severe dysfunction patterns predominating. The treatment outcomes of 22 patients who underwent vestibular rehabilitation are discussed. Prevention of bilateral vestibular paresis remains a high priority. PMID- 1900634 TI - Technique for transmission and immunoelectron microscopy of the human endolymphatic sac and vestibular epithelia. AB - A surgical technique is presented to obtain the entire vestibular aqueduct, containing the endolymphatic duct and sac as well as the vestibular epithelia, from the maculae and cristae during labyrinthectomy. The inner ear tissue was fixed in 3% glutaraldehyde, decalcified in 0.1 mol/L Na-EDTA, and routinely processed for transmission electron microscopy, including post-fixation with osmium tetroxide. Postembedding protein A-colloidal gold immunoelectron microscopy was performed after exposure of cellular antigenic sites by sodium metaperiodate. To validate this technique, thin sections from the crista ampullaris and the endolymphatic sac were incubated with antibodies raised against S-100, a protein present in specific types of neural tissue. Specific immunoreactivity was observed in the crista ampullaris, but not in the endolymphatic sac. The surgical biopsy technique described provides a means for the neuro-otologist to collect inner ear tissue from surgical patients that can be used for pathological studies using immunohistochemistry and electron microscopy. PMID- 1900635 TI - Cerebrospinal fluid leaks and meningitis in acoustic neuroma surgery. AB - Cerebrospinal fluid leaks and associated meningitis are the most common life threatening complications of surgery for acoustic neuromas. This retrospective study reviews 319 patients who had surgery for 321 acoustic tumors at the Sunnybrook Health Sciences Center, University of Toronto, from April 1975 to March 1990. Cerebrospinal fluid leaks occurred after 13.4% of primary tumor operations. Surgical repair was required in 6.2% of all patients; 4.4% needed more than one operation. Meningitis occurred in 5.3% of all patients. These complications were more common in larger tumors and after the combined translabyrinthine middle fossa approach. Transnasopharyngeal eustachian tube obliteration was used to stop recurrent cerebrospinal fluid leaks in two patients. PMID- 1900636 TI - An analysis of the retrolabyrinthine vs. the retrosigmoid vestibular nerve section. AB - Vestibular neurectomy is gaining widespread acceptance as a primary means of controlling medically refractory vertigo. However, debate continues over the adequacy of vestibular neurectomy within the cerebellopontine angle, long-term control, and the most appropriate surgical approach. To address these issues, we retrospectively reviewed 118 patients who underwent vestibular neurectomy between October 1984 and January 1988. Forty-two patients who underwent a retrolabyrinthine approach and 44 patients who underwent a retrosigmoid approach completed a written questionnaire and provided a recent audiogram. According to American Academy of Otolaryngology-Head and Neck Surgery guidelines, complete or substantial vertigo control was achieved and maintained in 95% of patients in both surgical groups. Hearing, tinnitus, and fullness results over the long term are variable. The advantages and disadvantages of the various vestibular neurectomy approaches will be detailed. On review of our results and surgical experience, we now prefer the retrosigmoid approach. PMID- 1900637 TI - Operative management of acoustic neuromas: the priority of neurologic function over complete resection. AB - The objective of surgical management of acoustic tumors is to remove them entirely and preserve facial nerve function and hearing when possible. A dilemma arises when it is not possible to remove the entire tumor without incurring additional neurologic deficits. Twenty patients who underwent intentional incomplete surgical removal of an acoustic neuroma to avoid further neurologic deficit were retrospectively reviewed. They were divided into a subtotal group (resection of less than 95% of tumor) and a near-total group (resection of 95% or more of tumor) and were followed yearly with either computed tomography or magnetic resonance imaging. The subtotal group was planned and consisted of elderly patients (mean age, 68.5 years) with large tumors (mean, 3.1 cm). The near-total group consisted of younger patients (mean age, 45.8 years) and smaller tumors (mean, 2.3 cm). The mean length of followup for all patients was 5.0 years. Ninety percent of patients had House grade I or II facial function post operatively. Radiologically detectable tumor regrowth occurred in only one patient, who was in the subtotal resection group. Near-total resection of acoustic tumor was not associated with radiologic evidence of regrowth of tumor for the period of observation. Within the limits of the follow-up period of this study, subtotal resection of acoustic neuroma in elderly patients was not associated with clinically significant recurrence in most patients and produced highly satisfactory rates of facial preservation with low surgical morbidity. PMID- 1900638 TI - Of primary importance. PMID- 1900639 TI - [Hazards of radiotherapy in the presence of a cardiac pacemaker]. AB - A patient with cardiac pacing operated for cancer of the breast received subsequent radiotherapy, first with a linear accelerator, then with a betatron. The pacemaker was found deprogrammed as a sequel to irradiation although care was taken to keep it outside the irradiation field. After reprogramming the pacemaker changed a second time spontaneously the given parameters indicating permanent damage by the irradiation. In such cases the exchange of the pacemaker is recommended. Precautionary measures ranging from surveillance to possibilities for reprogramming and even reanimation or pacemaker replacement should be assured prior to irradiation of patients with cardiac pacing. PMID- 1900640 TI - Cystic fibrosis: infection. AB - Recurrent and chronic pulmonary infection is still the major cause of morbidity and mortality in cystic fibrosis. Although respiratory viruses are responsible for some of the acute exacerbations of the pulmonary disease, bacteria, and in some patients Aspergillus fumigatus, are the most important pathogens. Staphylococcus aureus and Haemophilus influenzae are the most prevalent pathogens in cystic fibrosis of childhood, whereas Pseudomonas aeruginosa and in some centres also Pseudomonas cepacia predominate in older children and adult patients. The chronic Pseudomonas aeruginosa infection is peculiar, since it is predominantly an endobronchial infection in small bronchioles caused by mucoid, alginate producing strains which gradually lose most of the O-antigenic determinants of the lipopolysaccharide. Although P. aeruginosa produces a number of other toxins which may play a role initially, most if not all of the pathology is caused by immune complex mediated chronic inflammation. The bacteriological results of antipseudomonas chemotherapy are disappointing, as these bacteria are virtually never permanently eliminated. The clinical results of repeated maintenance chemotherapy every 3 months are, however, good, since it is possible to preserve lung function for years and keep the patients alive. Antiinflammatory treatment with steroids for years is used in some patients with benefit. PMID- 1900642 TI - Recombinase-mediated gene activation and site-specific integration in mammalian cells. AB - A binary system for gene activation and site-specific integration, based on the conditional recombination of transfected sequences mediated by the FLP recombinase from yeast, was implemented in mammalian cells. In several cell lines, FLP rapidly and precisely recombined copies of its specific target sequence to activate an otherwise silent beta-galactosidase reporter gene. Clones of marked cells were generated by excisional recombination within a chromosomally integrated copy of the silent reporter. By the reverse reaction, integration of transfected DNA was targeted to a specific chromosomal site. The results suggest that FLP could be used to mosaically activate or inactivate transgenes for analysis of vertebrate development, and to efficiently integrate transfected DNA at predetermined chromosomal locations. PMID- 1900641 TI - [Deficiency in immunoglobulin subclasses as cause of increased infection susceptibility--a family study]. AB - Within 3 generations 6 members of a family showed diminished serum concentrations of one or more immunoglobulin G (IgG) subclasses. In all 6 individuals IgG-2 levels were low, together with low IgG-3 and/or IgG-4 in 5, but all had normal values for total IgG. The proposita and her 2 children suffered from frequent severe respiratory infections. One child, now aged 11, has had an average of 3 such infections per year since birth, while the other, now aged 8 years, has had 4 episodes annually since birth. Recurrent infection only started at age 34 in the proposita. In these 3 patients a line immuno-binding assay showed diminished subclass-specific IgG-2 antibodies against bacterial polysaccharides. They were replaced by Sandoglobulin, an immunoglobulin for intravenous use. Under substitution by 6 g or 12 g infusions of Sandoglobulin per month no further infections occurred or the infections were clearly milder than before, and the Ig subclass levels became normal. It is concluded that in every case of recurrent respiratory infections of unusual severity suggesting an antibody deficiency, it is advisable to measure not only the total Ig classes (IgG, IgA and IgM) but also the IgG subclasses. The clinical relevance of an Ig subclass deficiency can be further substantiated by measuring subclass-specific antibodies. PMID- 1900643 TI - Stimulatory and inhibitory effects of dimethyl sulfoxide on microsomal aniline hydroxylase activity. AB - Dimethyl sulfoxide (DMSO) at a single dose of 3 ml/kg body wt, administered i.p. to male rats, caused a significant increase in the hepatic microsomal aniline hydroxylase activity. However, the level of cytochrome P-450, the activities of NADPH-cytochrome c reductase, benzphetamine N-demethylase and aminopyrine N demethylase were unchanged at 24 h post-treatment. DMSO interacted with control rat liver microsomes in vitro and produced a type II spectral change (peak at 420 nm and trough at 392 nm). On the other hand, liver microsomes from DMSO-treated rats gave qualitatively similar spectra, but with a higher magnitude of binding. Liver microsomes from DMSO-treated rats showed a 3.4-fold increase in Vmax for aniline hydroxylase, while Km was found to be the same when compared with control rat liver microsomes. In vitro addition of 6 mM DMSO to microsomal incubations from control and DMSO-treated rats caused a 9-fold and a 25-fold increase in Km, respectively, while Vmax values for aniline hydroxylase were unchanged. When DMSO (6 mM) was incubated with rat liver microsomes in the presence of NADPH, there was formation of formaldehyde. The results suggest an interaction of DMSO with microsomal cytochrome P-450. PMID- 1900644 TI - Effect of stable xenon on regional cerebral blood flow and the electroencephalogram in normal volunteers. AB - We evaluated the effects of breathing 35% stable xenon in 65% oxygen on regional cerebral blood flow and the electroencephalogram in 20 normal volunteers. We measured blood flow in 32 brain regions over both hemispheres with the xenon-133 intravenous injection technique in two protocols. In the first protocol (n = 10), a baseline study was followed by a second study during 5 minutes of breathing stable xenon; in the other protocol (n = 8), the baseline study was followed by a second study after 5 minutes of breathing stable xenon. Two volunteers were excluded due to excessive movements during the inhalation of stable xenon. Some of the remaining 18 volunteers had varying alterations of consciousness accompanied by electroencephalogram changes. After stable xenon inhalation the electroencephalogram returned to normal within 2-3 minutes. During stable xenon inhalation mean +/- SD PECO2 dropped significantly from 39.4 +/- 4.4 to 33.3 +/- 5.4 mm Hg in the first protocol and from 39.4 +/- 2.6 to 34.8 +/- 4.1 mm Hg in the second protocol due to hyperventilation in 13 volunteers. Mean regional cerebral blood flow increased significantly by 13.5-25.4% without correction for PECO2. In the first protocol regional cerebral blood flow increased by greater than 12% in 11-14 (depending on the flow parameter) of the 20 hemispheres. In the second protocol regional cerebral blood flow increased by greater than 12% in 9 13 of the 16 hemispheres. We conclude that cautious interpretation is necessary in the assessment of regional cerebral blood flow with 35% xenon-enhanced computed tomography. PMID- 1900645 TI - Effect of high-dose methylprednisolone and U74006F on eicosanoid synthesis after subarachnoid hemorrhage in rats. AB - Free radicals and lipid peroxidation of membrane fatty acids are thought to play a role in the pathogenesis of arterial vasospasm and the physiopathologic patterns of neuronal damage after subarachnoid hemorrhage. We have evaluated the effects of treatment with either high-dose methylprednisolone every 8 hours or a single dose of U74006F on the temporal profile of ex vivo synthesis of four selected eicosanoids in brain slices after experimental induction of subarachnoid hemorrhage in rats. Prostaglandins D2 and E2, prostacyclin and leukotriene C4 levels were determined by radioimmunoassay after 1-hour incubation of the brain slices. The synthesis of prostaglandin D2 and 6-ketoprostaglandin F1 alpha at 48 hours after subarachnoid hemorrhage was significantly higher when compared to sham-operated animals (p = 0.01); prostaglandin E2 release was significantly enhanced at 6 hours after subarachnoid hemorrhage (p = 0.01). The release of the lipoxygenase metabolite was significantly enhanced at 1, 6, and 48 hours after subarachnoid hemorrhage induction. Both treatment regimens significantly reduced the ex vivo synthesis of prostaglandin D2, prostaglandin E2, and leukotriene C4 at 1, 6, and 48 hours after subarachnoid hemorrhage, whereas the effects on 6 ketoprostaglandin F1 alpha synthesis differed in the two treatment groups. U74006F enhanced the synthesis of prostacyclin metabolite in the early phase after subarachnoid hemorrhage, and high-dose methylprednisolone reduced the increasing synthesis at 48 hours. A strict comparison between the two treatments was not possible because of the different modalities of administration. However, these data suggest that the antioxidant effect of single-dose treatment with U74006F influenced the early and delayed effects on enzymatic lipid peroxidation, whereas the effects of methylprednisolone administration every 8 hours were more significant in the delayed phase. PMID- 1900646 TI - Cerebrovascular CO2 reactivity during delayed vasospasm in a canine model of subarachnoid hemorrhage. AB - While the in vitro reactivity of cerebral conducting vessels following subarachnoid hemorrhage has been extensively studied, in vivo cerebrovascular CO2 reactivity has not been systematically investigated. We tested the hypothesis that, in the canine model of subarachnoid hemorrhage, the rise in cerebral blood flow normally seen with hypercapnia is blunted during delayed vasospasm. Four groups of animals were studied: one received two 4-ml subarachnoid injections of nonheparinized arterial blood into the cisterna magna (n = 8), one received three subarachnoid injections of 5 ml blood (n = 5), one received two subarachnoid injections of 4 ml saline (n = 5), and a control group (n = 5) had no subarachnoid injections or angiography. Basilar artery diameter was measured from baseline and follow-up angiography. We determined CO2 reactivity by randomly varying the concentration of inspired CO2 and measuring regional cerebral blood flow with radiolabeled microspheres. Basilar artery diameter was not affected by saline injection and was reduced by 26 +/- 2.9% in the two-hemorrhage group and 55 +/- 1.9% in the three-hemorrhage group. Baseline cerebral blood flow and CO2 reactivity were similar in all four groups. We conclude that, in this model of delayed vasospasm, regional cerebral vascular CO2 reactivity is intact and extrapolation of in vitro data regarding basilar artery diameter and reactivity to cerebral blood flow must be done cautiously. PMID- 1900647 TI - Effect of carbon dioxide and oxygen on endothelin production by cultured porcine cerebral endothelial cells. AB - We have previously reported the production of endothelin, a potent vasoconstrictor peptide, by porcine cerebral microvessel endothelia and suggested its important role in the regulation of local blood flow within the brain. In our present study, radioimmunoassay with anti-porcine endothelin antiserum revealed that endothelin, produced by cerebral microvessel endothelia grown on a filter, is released mainly to the basement membrane side, not the vascular lumen side. This finding suggests that endothelin constricts arterioles locally where it is produced by endothelia. We also found that cerebral microvessel endothelia produce less endothelin under low oxygen pressure and more endothelin under low carbon dioxide pressure. Our results suggest that endothelin has a role in the regulation of cerebral blood flow in response to oxygen and carbon dioxide pressure. PMID- 1900649 TI - Two cases of "hrB-like" autoantibodies appearing as alloantibodies. AB - Two cases are described in which autoantibodies mimicked alloantibodies. The direct antiglobulin test (DAT) on the red cells (RBCs) from both patients was negative when routine manual hexadimethrine bromide (Polybrene) and enzyme-linked antiglobulin techniques were used. The RBCs also did not react on direct bromelin and direct Polybrene tests. However, an "hrB-like" antibody was eluted from the RBCs of both patients. The sera from these patients reacted with all e+ hrB+ RBCs but not with e+ hrB-, e-, or their own RBCs. The antibody in the serum of one patient was not adsorbed by R2R2 RBCs. Serologic tests initially suggested (by direct testing and adsorption studies) that the serum antibodies were alloantibodies rather than autoantibodies. RBCs taken from one patient, 8 months after her sample was first referred to our laboratory, reacted with a serum sample from her first admission. An RBC sample taken from the other patient, initially typed e+ and hrB- but 1 month later typed e+ and hrB+ by using the same anti-hrB sera, was used to test the earlier samples. PMID- 1900648 TI - Commentary on the safety of red cells preserved in extended-storage media for neonatal transfusions. AB - Red cells preserved in extended-storage media are the standard product dispensed by many regional blood centers. When the red cells are intended for neonatal transfusion, concern exists about the safety of the relatively high quantities of additives present in these media. Definitive studies to address these concerns are not available. Therefore, to estimate the effects of additives and to delineate circumstances in which they might be harmful, the quantities transfused in defined clinical settings were calculated, and the following recommendations are offered for transfusing infants less than 4 months of age. First, red cells preserved in extended-storage media should present no substantive risks when used for small-volume (approximately 10 mL/kg) transfusions of premature infants and can be used without additional processing. Second, the risks of the most premature neonatal patients or those with severe renal and/or hepatic insufficiency cannot be defined clearly, and, because data are not available to ensure safety for these infants, removal of the additive medium and resuspension of the red cells in saline or albumin solution immediately before transfusion are recommended. Third, following a similar rationale, it seems prudent to avoid using entire units of red cells preserved in extended-storage media in massive transfusion settings (e.g., exchange transfusion, cardiac surgery, and extracorporeal membrane oxygenation). In these settings, the preservative medium should be removed and the red cells resuspended in the fluid that is most appropriate for the procedure that is planned. It must be emphasized that these recommendations are based on calculations and hypothetical settings, not actual data. Accordingly, they are tentative and should be altered as definitive information becomes available. PMID- 1900650 TI - Controversies in transfusion medicine. Testing for Du: con. PMID- 1900651 TI - Controversies in transfusion medicine. D(u) testing: pro. PMID- 1900652 TI - Diagnostic relevance of suppressed basal concentrations of TSH compared with the negative TRH test in detection and exclusion of hyperthyroidism. AB - To evaluate the sensitivity of basal TSH concentrations as determined by an "ultrasensitive" IRMA-assay (RIA-gnost h-TSH-monoclonal, Behring) versus a "negative" TRH test (defined as an increment of TSH less than or equal to 0.2 mU/l 20 min after administration of 400 micrograms TRH iv) in the diagnosis of hyperthyroidism we examined 193 consecutive patients from our thyroid outpatient clinic: 34 patients displayed hyperthyroidism (total T4: 184.4 +/- 26.0 mumol/l, effective thyroxine index: 1.25 +/- 0.08), whereas 12 had isolated T3 hyperthyroidism (total T3: 3.47 +/- 0.48 nmol/l). Employing the producer's definition of subnormal ("suppressed") bTSH concentrations (less than or equal to 0.1 mU/l), only 19 (41.3%) hyperthyroid patients would have been detected; on the other hand, one euthyroid patient would have been recognized false positively as hyperthyroid. Using the TRH test as criterion led to the correct diagnosis in 42 (sensitivity: 91.3%) hyperthyroid patients, whereas two had low bTSH concentrations (less than or equal to 0.5 mU/l), but a normal TSH response to TRH (greater than 2.0 mU/l). Raising the threshold concentration to 0.2 and, subsequently, to 0.4 mU TSH/l increased the number of correct results to 38 (sensitivity: 82.6%) and 43 (93.5%), respectively. This was associated with a concomitant decrease in specificity in the diagnosis of hyperthyroidism from 93.7 (0.1 mU/l) to 27.9% (0.4 mU/l). In conclusion, despite ultrasensitive methods for estimation of low TSH concentrations, the TRH test remains an irreplaceable tool for the correct diagnosis of hyperthyroidism. PMID- 1900653 TI - Free thyroxine and 3,3',5'-triiodothyronine levels in cerebrospinal fluid in patients with endogenous depression. AB - Total and free concentrations of T4 and rT3 in serum and cerebrospinal fluid were estimated by ultrafiltration in 12 patients with unipolar endogenous depression before and after electroconvulsive treatment. Recovery from depression resulted in a decrease in CSF concentrations of free T4 (median) (26.2 to 21.4 pmol/l, p less than 0.02) and free rT3 (14.1 to 12.3 pmol/l, p less than 0.05). Concentrations of free T4 in the cerebrospinal fluid were lower than those in serum (p less than 0.02), the ratio being 0.6. In contrast, levels of free rT3 in the cerebrospinal fluid were considerably higher than those found in serum (p less than 0.01), the ratio being 25. These ratios did not change following recovery from depression. In 9 patients with nonthyroidal somatic illness, concentrations of free T4 and rT3 in the cerebrospinal fluid were similar to those found in patients with endogenous depression, whereas 4 hypothyroid patients and one hyperthyroid patient had considerably lower and higher, respectively, concentrations of both free T4 and rT3. In conclusion, levels of free T4 and free rT3 in the cerebrospinal fluid are increased during depression compared with levels after recovery, probably reflecting an increased supply of T4 from serum and an increased production of rT3 from T4 in the brain. The data also suggest that the transport of iodothyronines between serum and the cerebrospinal fluid is restricted. PMID- 1900654 TI - Autonomous progesterone secretion from the bovine corpus luteum in vitro. AB - While the regulation of progesterone secretion from the corpus luteum by LH has been convincingly demonstrated, the secretory patterns in the absence of any pituitary LH inputs are yet unclear. Consequently, we investigated the progesterone secretion by an in vitro perifusion system to characterize spontaneous progesterone release from the isolated bovine corpus luteum. Slices (120 mg) of midluteal corpora lutea were placed in perifusion chambers and continuously perifused by Medium-199 for 160-320 min. Progesterone was determined by radioimmunoassay in the effluent fractions collected at 2-min intervals. The spontaneous progesterone release from all bovine corpora lutea was pulsatile. Pulses were observed at mean (+/- SEM) intervals of 17.7 +/- 1.5 min with amplitudes of 6.7 +/- 0.5 ng and release rates of 29.5 +/- 2.4 ng.ml-1.(2 min)-1 (N = 5). Addition of 6.7 nmol/l hCG to the perifusion medium appeared to increase the pulse amplitudes and release rates (195 +/- 25% over unstimulated conditions), but did not change the pulse frequencies (N = 3). Perifusions with calcium-free medium containing 50 mumol/l verapamil and 20 mmol/l EGTA tended to suppress the pulse frequencies and amplitudes of this spontaneous progesterone release, whereas addition of hCG reversed this decrease again (N = 3). When prostaglandin activity was inhibited by 100 mumol/l indomethacin added to the perifusion medium, both pulse frequencies and amplitudes of this progesterone release were enhanced (N = 4). During perifusions with 100 mumol/l of the anti progesterone ZK 96.734, both the pulse frequencies and amplitudes increased (N = 4). These studies demonstrate an episodic progesterone release from the bovine corpus luteum perifused in vitro.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1900655 TI - Sensitivity of thyrotropin secretion to TSH-releasing hormone in food-restricted rats. AB - The aim of the present study was to identify the mechanisms involved in the reduction of TSH secretion during prolonged food restriction. The basal TSH secretion rate, the TSH secreted in response to TRH, both in vivo and in vitro, and the TSH, nuclear T3, and plasma membrane TRH binding sites in the pituitary were determined in rats receiving 75% (FR75), 50% (FR50) and 25% (FR25) of the food consumed by the ad libitum fed rats (controls). The basal TSH secretion rate (microgram.h-1.(100 g)-1) in FR75, FR50 and FR25 groups were decreased by 19, 42 and 74% of control values, respectively, whereas the TSH secreted in response to TRH in vivo and in vitro was reduced by 21 and 13% in FR50, and 55 and 44% in FR25, respectively, of the corresponding control values. Food restriction increased the TRH binding sites from 229 in controls to 322, 479 and 521 (fmol/mg protein), in FR75, FR50 and FR25 groups, respectively, whereas the opposite was seen in nuclear T3(controls 862, FR75 841, FR50 342 FR25 233 fmol/mg DNA). Moreover, a decrease in the pituitary TSH concentration was observed in FR50 and FR25 rats. The data suggest that an alteration in the amount of TRH reaching the pituitary gland is probably the main responsible for the low plasma TSH values during food restriction. However, an inhibitory effect at the pituitary level cannot be ruled out. PMID- 1900656 TI - Frontal lobe seizures and epilepsies in neurobehavioral disorders. PMID- 1900657 TI - Improved speed and accuracy of calculations with a programmable calculator in pediatric emergency scenarios. AB - Both mathematical and selection errors may occur when ordering drug or fluid therapy in a busy emergency department. In an attempt to improve the speed and accuracy of such calculations, we programmed a hand-held calculator to assist in drug and intravenous fluid therapy dosages and rates for three emergency situations: diabetic ketoacidosis, asthma, and asystole. Performance by 58 subjects at various levels of training was compared when using either the programmable calculator or standard materials and methods. When standard methods were used, an average of 30.6 minutes was needed to complete the three scenarios, with an accuracy of 73%; by contrast, use of programmable calculator resulted in a significant decline in time needed to calculate doses (an average of only 8.5 minutes), with an improved accuracy of 98%. The use of a programmable calculator can result in a significant improvement in both speed and accuracy of drug and fluid selection and dosage and rate calculations, regardless of the level of the subject's medical training. PMID- 1900658 TI - Cephalosporin confusion--one simple solution? PMID- 1900659 TI - Effect of computer software on time required to prepare parenteral nutrient solutions. AB - Pharmacist and technician times required for the preparation of parenteral nutrient (PN) solutions were studied before and after the introduction of a software package that is used with an automated compounder. At a 580-bed teaching hospital, work sampling was used to collect data on how time was spent by personnel in the i.v. admixture pharmacy during six-week periods before and after the introduction of software that calculates the quantities of PN solution ingredients on a computer-generated work sheet and prints labels. The second data collection period began when the software had been in use for four months. In the second study period, there was a significant decrease (28%) in total pharmacist time spent per PN solution; the mean +/- S.D. pharmacist times per PN solution per day for the two study periods were 14.03 +/- 3.24 minutes and 10.12 +/- 1.61 minutes, respectively. There were also significant decreases in pharmacist time spent performing calculations, checking calculations, and typing labels. After introduction of the software, technicians spent significantly less time typing labels and pumping base solutions. Overall, technicians spent significantly less time per PN solution in the second study period (20.15 +/- 3.50 versus 17.82 +/- 1.94 minutes). Use of the software allowed pharmacist staffing in the i.v. admixture pharmacy to be reduced, and the pharmacy resources were reallocated toward the provision of clinical services. The generation of PN labels and calculation worksheets by computer software reduced pharmacist and technician time requirements for PN solution preparation. PMID- 1900660 TI - Cerebral ischemic events associated with endocarditis, retinal vascular disease, and lupus anticoagulant. AB - PURPOSE: A group of young patients presenting with cerebral ischemic events, endocardial lesions, and lupus anticoagulant is described in order to highlight the common clinical laboratory features. PATIENTS AND METHODS: Fourteen consecutive patients (10 females, age range 17 to 53 years [mean 38 years]) at onset of symptoms of cerebral ischemia who had evidence of the lupus anticoagulant syndrome and were being followed prospectively are reviewed. All patients had abnormal phospholipid-dependent coagulation test results, and most had anticardiolipin antibody at the time of presentation. Three of 14 had four or more American Rheumatism Association criteria for definite systemic lupus erythematosus and the remaining patients were considered to have primary lupus anticoagulant syndrome. RESULTS: The common features among these patients included at least one cerebral ischemic event at presentation (stroke or transient ischemic attack), or recurrent episodes suggesting cerebral ischemia (amaurosis fugax, recurrent severe migraine headaches), livedo reticularis, endocardial valvular lesions noted on echocardiography (11 mitral, two aortic valve) that were often associated with discrete vegetations, retinal vascular lesions, and computed tomographic/magnetic resonance imaging scanning or angiographic evidence of multiple cerebral infarction. Venous thromboembolic events were uncommon (three of 14). Common laboratory studies included thrombocytopenia (10 of 14), positive direct Coombs' test result (11 of 14), and hypocomplementemia (11 of 14). Follow-up after initial treatment with either salicylates or anticoagulant therapy (warfarin) for up to 10 years indicated that while many patients had recurrent symptoms suggesting cerebral ischemia, major stroke syndromes did not recur nor new episodes emerge. CONCLUSION: The combination of multiple cerebral ischemic lesions and endocardial lesions, including valvular vegetations, suggests that these cerebral ischemic events represent cerebral emboli, and that these cerebral embolic events originate from vegetative lesions on the mitral or, less commonly, aortic valve, in association with lupus anticoagulant. PMID- 1900661 TI - Flow velocity waveforms of the fetal circulation preceding fetal death in a case of lupus anticoagulant. AB - Flow velocity waveforms of the vascular system were evaluated at 25 weeks 2 days and 27 weeks 5 days of gestation in the case of a severely growth-retarded fetus. At the first scan, the cerebral vessels displayed low pulsatility indexes, reflecting the brain-sparing pattern that characterizes fetal stress. This compensatory reduction was lost at the time of the second, "preterminal" scan. PMID- 1900662 TI - Decreased levels of polyunsaturated fatty acids in preeclampsia. AB - Plasma levels of polyunsaturated fatty acids in the n-3 and n-6 classes, which include linoleic, linolenic, arachidonic, eicosapentaenoic, and docosahexaenoic acids, were quantified with high-performance liquid chromatography in nonpregnant volunteers and in patients with normal pregnancies or preeclampsia at term. The total polyunsaturated fatty acid levels were not significantly different between nonpregnant and normal pregnant patients but was significantly lower in the preeclamptic patients compared with normal pregnant patients. This decreased level could represent altered fatty acid metabolism or altered storage and mobilization from lipid pools. Compared with nonpregnant patients, normal pregnant patients had significantly higher levels of eicosapentaenoic and docosahexaenoic acid. This may reflect normal physiologic changes in pregnancy, and the decreased level of eicosapentaenoic acid seen in preeclamptic patients may play a significant role in the pathophysiology of preeclampsia. PMID- 1900663 TI - Combination antimicrobial therapy in the treatment of acute pelvic inflammatory disease. AB - We compared the clinical and microbiologic efficacy of two broad-spectrum combination antimicrobial regimens in the treatment of 148 patients with acute pelvic inflammatory disease. Patients were randomized to inpatient treatment with either cefoxitin and doxycycline (n = 75) or clindamycin and tobramycin (n = 73). These antibiotics were administered intravenously for at least 4 days, and up to 48 hours beyond defervescence. Patients were discharged on a regimen of oral doxycycline or clindamycin in accordance with the intravenous regimen to complete a total duration of therapy of 2 weeks. Neisseria gonorrhoeae (53%) and Chlamydia trachomatis (31%) were the microorganisms that were isolated most frequently from the genital tract of enrolled patients. At follow-up, N. gonorrhoeae was isolated in two patients, and C. trachomatis was isolated in none. The overall initial favorable response rate to combination antimicrobial therapy was 98.5% (130/132) in patients with uncomplicated pelvic inflammatory disease and 81% (13/16) in patients with pelvic inflammatory disease that was complicated by tuboovarian abscess. A greater than 70% decrease in abdominal tenderness score occurred in 89% of 111 patients within 6 weeks of hospital discharge. There were no significant differences between antibiotic treatment groups in any response categories or in toxicity. During the initial hospitalization, five patients (three with tuboovarian abscess; one with a pyosalpinx, and one with intractable acute and chronic pelvic inflammatory disease) required surgical intervention. These results support the recommendation to use broad-spectrum combination antimicrobial therapy for the treatment of acute pelvic inflammatory disease. PMID- 1900664 TI - Meconium-stained amniotic fluid: a risk factor for microbial invasion of the amniotic cavity. AB - The purpose of this study was to determine whether meconium-stained amniotic fluid is a marker for microbial invasion of the amniotic cavity. Amniocentesis was performed on 707 patients presenting with preterm labor and intact membranes. Meconium-stained amniotic fluid was present in 4.2% (30/707) of patients with preterm labor. The prevalence of positive amniotic fluid cultures was significantly higher in women with meconium-stained amniotic fluid than in women with clear fluid (33% [10/30] vs 11% [75/677]; p = 0.001; odds ratio = 4.01; 95% confidence interval = 1.6 to 9.4). Patients with meconium-stained amniotic fluid were also more likely to have failed tocolysis and delivered a preterm neonate more frequently than patients with clear fluid (83% [25/30] vs 38% (258/677); p = 0.0001; odds ratio = 8.1; 95% confidence interval = 2.9 to 24.4). We conclude that meconium-stained amniotic fluid is a risk factor for microbial invasion of the amniotic cavity and preterm delivery in women with preterm labor and intact membranes. PMID- 1900665 TI - A comparison of flurbiprofen, tranexamic acid, and a levonorgestrel-releasing intrauterine contraceptive device in the treatment of idiopathic menorrhagia. AB - Treatment with flurbiprofen (100 mg twice a day for 5 days), tranexamic acid (1.5 gm three times a day for 3 days and 1 gm twice a day for another 2 days), and an intrauterine contraceptive device releasing 20 micrograms levonorgestrel per day was compared in women with idiopathic menorrhagia. The menstrual blood loss during two control periods in 15 women subsequently treated with flurbiprofen and tranexamic acid was 295 +/- 52 ml and 203 +/- 25.2 ml in the 16 women later fitted with a levonorgestrel-releasing intrauterine contraceptive device. Menstrual blood loss was reduced by all three forms of treatment. The reduction in menstrual blood loss expressed as a percentage of the mean of two control cycles for each form of treatment was as follows: flurbiprofen, 20.7% +/- 9.9%; tranexamic acid, 44.4% +/- 8.3%; levonorgestrel-releasing intrauterine contraceptive device after 3 months, 81.6% +/- 4.5%; levonorgestrel-releasing intrauterine contraceptive device after 6 months, 88.0% +/- 3.1%; levonorgestrel releasing intrauterine contraceptive device after 12 months, 95.8% +/- 1.2%. The reduction in menstrual blood loss achieved by the levonorgestrel-releasing intrauterine contraceptive device was greater than that recorded with flurbiprofen (p less than 0.001) and tranexamic acid (p less than 0.01), and was greater for tranexamic acid when compared with flurbiprofen (p less than 0.05). The levonorgestrel-releasing intrauterine contraceptive device was the only form of treatment to reduce mean menstrual blood loss below 80 ml per menstruation, the upper limit of normal menstrual blood loss. PMID- 1900666 TI - Differential expression of amino acid transport systems A and ASC during erythroleukemia cell differentiation. AB - The human erythroleukemic cell K-562 serves as an in vitro model to study changes in cell surface antigens and mechanisms regulating globin gene expression associated with in vivo erythropoiesis. In this report we have examined the regulation of amino acid transport systems, in particular, systems A and ASC, during differentiation of erythroleukemic cells. For additional comparison we examined the uptake of leucine, 3-aminoendobicyclo-(3,2,1)-octane-3-carboxylic acid (BCO), arginine, and glutamate. Hexamethylene-bis-acetamide (HMBA), dimethyl sulfoxide, and butyrate induce cell differentiation with a block in G1-G0 phase of the cell cycle. These agents caused a significant downregulation of 2 (methylamino)isobutyric acid uptake by system A. In contrast, the Na(+)-dependent threonine uptake by system ASC remained unaltered. The uptake of leucine, BCO, arginine, and glutamate by as yet unidentified systems was, however, stimulated after HMBA treatment. Hemin, a potent inducer of hemoglobin synthesis in K-562 cells, does not block cell cycle events and, interestingly, had no significant effect on both systems A and ASC. These differences in inducer actions suggest that system A activity may be related to specific stages of cell differentiation and perhaps to other cellular signals. PMID- 1900667 TI - Insulin resistance in normal rats infused with glucose for 72 h. AB - Insulin resistance is accentuated during periods of poor metabolic control in human non-insulin-dependent diabetes mellitus. The role of hyperglycemia in this suppression of insulin action is not clear. If glucose impairs insulin action, then the effect should be reproducible in vivo in tissues of normal intact rats. To test this possibility, normal rats were continuously administered 50% glucose in water (60-66 mg.kg-1.min-1) via an indwelling jugular catheter. After 72 h, these animals were hyperglycemic, hyperinsulinemic, and glucosuric compared with control rats infused for 72 h with normal saline (P less than 0.01). Basal glucose uptake in vivo was greater in muscle of glucose-infused rats. Insulin stimulated glucose uptake in vivo and in vitro (by perfused hindquarters and isolated adipocytes) were suppressed in the glucose-infused group (P less than 0.01). Glycogen synthase activity was reduced 40% in extracts of muscle and adipose tissue of hyperglycemic rats. Basal and isoproterenol-stimulated lipolysis were increased, whereas insulin suppression of lipolysis was blunted in adipocytes from glucose-infused animals (P less than 0.01). Glucose infusion did not alter insulin binding by isolated adipocytes or solubilized skeletal muscle insulin receptors. These results suggest that a 72-h in vivo glucose infusion impaired insulin action in muscle and adipose tissue of normal rats by inducing postbinding defects similar to those observed in human diabetes mellitus during intervals of deteriorated metabolic control. PMID- 1900668 TI - Glycine turnover and oxidation and hepatic serine synthesis from glycine in fetal lambs. AB - [1-13C]- and [1-14C]glycine were infused into chronically catheterized fetal lambs via a brachial vein. At tracer glycine steady state, samples were collected from the fetal abdominal aorta, umbilical vein, and fetal hepatic vein and from the maternal femoral artery and uterine vein. The samples were analyzed for plasma glycine and serine, for glycine and serine 13C atom% excess (APE), and for whole blood 14CO2 and O2 concentrations. Fetal plasma glycine disposal rate (DR) was 12.4 +/- 0.8 mumol.min-1.kg fetus-1.CO2 production from decarboxylation of fetal plasma glycine was 1.63 +/- 0.16 mumol.min-1.kg fetus-1 and represented 12.3 +/- 0.7% of DR. Approximately 50% of infused tracer glycine was taken up by the fetal liver with the release of labeled serine and CO2 in the fetal circulation. There was no detectable efflux of tracer glycine from the placenta into the maternal circulation. The tracer production of serine and CO2 accounted for 23 and 17%, respectively, of the hepatic tracer glycine uptake. The labeled CO2 released by the liver was a large fraction (approximately 70%) of the labeled CO2 produced by the fetus. The serine-to-glycine APE ratio in fetal plasma was approximately 5%. These results indicate that the fetal liver is the major site of fetal plasma glycine decarboxylation and of serine synthesis from plasma glycine. PMID- 1900669 TI - Epinephrine inhibits insulin-mediated glycogenesis but enhances glycolysis in human skeletal muscle. AB - The effect of epinephrine (E) infusion on insulin-mediated glucose metabolism in humans has been studied. Eight glucose-tolerant men were studied on two separate occasions: 1) during 120 min of euglycemic hyperinsulinemia (UH, approximately 5 mM; 40 mU.m-2.min-1); and 2) during UH while E was infused (UHE, 0.05 microgram.kg-1.min-1). Biopsies were taken from the quadriceps femoris muscle before and after each clamp. Glucose disposal, correcting for endogenous glucose production, was 36 +/- 3 and 18 +/- 2 (SE) mumol.kg fat-free mass (FFM)-1.min-1 during the last 40 min of UH and UHE, respectively (P less than 0.001). Nonoxidative glucose disposal (presumably glycogenesis) averaged 23.0 +/- 3.0 and 4.0 +/- 1.1 (P less than 0.001), whereas carbohydrate oxidation (which is proportional to glycolysis) averaged 13.1 +/- 1.4 and 15.3 +/- 1.1 mumol.kg FFM 1.min-1 (P less than 0.05) during UH and UHE, respectively. UHE resulted in significantly higher contents of UDP-glucose, hexose monophosphates, postphosphofructokinase intermediates, and glucose 1,6-bisphosphate (G-1,6-P2) in muscle (P less than 0.05-0.001), but there were no significant differences in high-energy phosphates or fructose 2,6-bisphosphate (F-2,6-P2) between treatments. Fractional activities of phosphorylase increased (P less than 0.01), and glycogen synthase decreased (P less than 0.001) during UHE. It is concluded that E inhibits insulin-mediated glycogenesis because of an inactivation of glycogen synthase and an activation of glycogenolysis. E also appears to inhibit insulin-mediated glucose utilization, at least partly, because of an increase in G-6-phosphate (which inhibits hexokinase) and enhances glycolysis by G-1,6-P2-, fructose 6-phosphate-, and F-1,6-P2-mediated activation of PFK. PMID- 1900670 TI - Age-related alterations in pulsatile secretion of TSH: role of dopaminergic regulation. AB - To investigate the influence of aging on dopaminergic modulation of pulsatile thyrotropin (TSH) secretion, we examined changes in circulating TSH levels during the day and night, with and without a dopamine antagonist metoclopramide, in healthy young (20-35 yr old) and old (69-83 yr old) subjects, with the use of cluster analysis. Baseline thyroid function tests including serum thyroxine, 3,5,3'-triiodothyronine (T3), T3 resin uptake, and TSH and the response of TSH to thyrotropin-releasing hormone were within normal limits in young and old subjects, and antimicrosomal and anti-thyroglobulin antibodies were absent in all participants. Pulsatile TSH secretion was identified in all subjects, and as a group there were significant increases in nocturnal peak height (P less than 0.01), amplitude (P less than 0.01), and mean TSH (P less than 0.001). TSH pulse amplitude increased 160% (P less than 0.05) at night compared with day in the young but was unchanged at night in the old. After the administration of metoclopramide there was a significant increase in peak height (P less than 0.01), amplitude (P less than 0.01), and mean TSH (P less than 0.01). However, the effect of metoclopramide was different in young and old subjects. In the young, daytime administration of metoclopramide increased TSH pulse height (P less than 0.02) and mean TSH (P less than 0.05); pulse parameters remained unchanged at night. In comparison, in old subjects after metoclopramide, pulse parameters were unchanged during the day but pulse amplitude significantly (P less than 0.01) increased at night. TSH pulse frequency remained stable with age and was unaltered after metoclopramide.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1900671 TI - Postprandial decrease in HDL cholesterol and HDL apo A-I in normal subjects in relation to triglyceride metabolism. AB - The postprandial lipoprotein metabolism is important since it determines the circulation of potentially atherogenic particles and influences the metabolism of high-density lipoproteins (HDL) in a complex manner that is at present not completely understood. Therefore, the short-term (24-h) changes in postprandial lipoprotein metabolism, including retinyl palmitate (RP), apolipoprotein A-I (apo A-I), and apolipoprotein B, were studied in relation to postheparin lipolytic activities in six healthy normolipidemic men after an oral RP fat tolerance test. The fat load (98 g) was cleared in 7 h, because the triglyceride (TG) concentrations had returned to initial values (0.72 +/- 0.31 mmol/l) at that time. RP showed a peak in plasma at 4 and 5 h but remained present in chylomicron (remnants) in low concentrations after 8 and 24 h. After the fat load, HDL cholesterol and HDL-associated apo A-I showed a significant decrease in concentration of 35 and 29%, respectively. The decrease coincided with the increase in chylomicron remnants and the transient appearance of TG-enriched HDL. Hepatic lipase was correlated to both the initial HDL cholesterol concentration as well as the peak concentration of TG in chylomicron remnants, suggesting that it could be one of the regulating common physiological pathways in postprandial HDL and TG metabolism. In the subjects studied, the atherogenic potential of plasma increased in response to an oral fat load, characterized by a decrease in HDL cholesterol and HDL-associated apo A-I. PMID- 1900672 TI - Thyroxine and cortisone cooperate to modulate postnatal intestinal enzyme differentiation in the rat. AB - Interactions of cortisone and thyroxine (T4) in modulating jejunal sucrase and lactase expression were studied in rats during early postnatal life. Cortisone (50 micrograms/g body wt) precociously induced sucrase activity in days 5-16 rats and enhanced activity thereafter until day 22. T4 (1 microgram/g) plus cortisone evoked greater sucrase expression in day 9 or younger rats. T4 did not induce sucrase expression until day 13. Lactase activity was enhanced in rats younger than day 9 by cortisone, and this effect was abolished when T4 was added. In days 19 and 22 rats, cortisone depressed lactase; with T4, lactase activity was further decreased. T4 alone did not suppress lactase activity until day 19. Quantitation of jejunal enzyme content showed that sucrase catalytic activity was higher in day 22 than 19 or younger rats and lower in rats given T4 than cortisone. In contrast, lactase activity remained constant in all animal groups. In vivo [35S]methionine-labeling studies using day 9 rats showed that cortisone induced de novo synthesis of sucrase and increased 35S incorporation into lactase. Cortisone plus T4 increased 35S incorporation into sucrase further and significantly increased 35S incorporation into lactase. We conclude that 1) cortisone and T4 cooperatively stimulate sucrase expression and reduce lactase activity during early postnatal life and 2) reduction in lactase activity accompanied by increase in lactase synthesis suggests that cortisone and T4 regulate lactase activity at posttranslational level. PMID- 1900673 TI - Intestinal lactase expression and epithelial cell transit in hormone-treated suckling rats. AB - Cortisone- and/or thyroxine (T4)-induced changes in jejunal lactase activity and epithelial cell migration were studied to determine the relationship of these two events. In suckling rats given a single dose of cortisone on day 6, jejunal lactase activity increased by 37% and cell turnover rate by 95% 3 days later, whereas T4 alone induced no changes. After cortisone plus T4, jejunal lactase activity decreased by 23% while cell turnover rate increased by 176%. Among all animal groups, the patterns of lactase expression along the crypt-villus (C-V) axis were similar, being low at the C-V junction, increasing to a high plateau at the mid- or third quarter villus level, and decreasing slightly at the villus tip. The calculated epithelial cell age at half maximum lactase expression in cortisone-treated and cortisone plus T4-treated rats was 30 and 53% younger than in control rats. Maximum lactase activity in villus cells was approximately 45% higher in cortisone-treated than in control or cortisone plus T4-treated rats. Parallel measurements of sucrase and lactase activities along C-V axis showed elevated lactase activity at higher villus positions than lead sucrase activity, suggesting that cortisone action occurs in villus cells. Thus jejunal lactase expression may be modulated by 1) adjusting villus cell age required for maximum expression, 2) altering the level of lactase activity in villus cells, and 3) changing the turnover rate of lactase containing epithelial cells. PMID- 1900674 TI - Transport of L-proline and alpha-methyl-D-glucoside by chicken proximal cecum during development. AB - We examined the characteristics of amino acid and sugar absorption by the proximal cecum (PC) of chickens during posthatch development. Rates of absorption of L-proline (Pro) and alpha-methyl-D-glucoside (MG) were measured at 2 days, 5 wk, and 13 wk after hatch with an in vitro everted-sleeve method. For each age, pieces of PC and midjejunum were incubated in solutions containing 0.1-50 mM Pro or MG, and the active and passive components of Pro and MG absorption were determined. Five conclusions may be stated. 1) There are two carrier-mediated transport systems for Pro in the PC: a higher capacity Na(+)-dependent system (Vmax between 1.6 and 3.2 nmol.mg-1.min-1), and a lower capacity Na(+) independent system (Vmax 0.3-0.8 nmol.mg-1.min-1). 2) Whereas both Pro transport systems are present in the PC at 5 and 13 wk, only the Na(+)-dependent system was found at 2 days. Although rates of transport per milligram tissue by the Na(+) dependent system fell during development, when rates were normalized to nominal surface area, Vmax was significantly higher in the 5-wk-old group than in the other groups. 3) MG transport is by a Na(+)-dependent system. Vmax values (nmol.mg-1.min-1) were 0.32 (2 days), less than 0.43 (5 wk), and = 0.55 (13 wk). These differences were not affected by normalization to surface area. 4) Because at physiological concentrations passive influx of Pro and MG would be negligible, absorption of amino acids and sugars by the PC would be dependent on the presence of carrier-mediated systems.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1900675 TI - Characteristics of luminal bicarbonate secretion by rat cecum in vitro. AB - Under in vitro conditions the rat cecum transported HCO3- from the serosal to an unbuffered solution in contact with the mucosal side [Js----m = 7.12 +/- 0.18 mumol.cm-2.h-1 (n = 149)]. With reversed tissues, a significantly lower flux was obtained [Jm----s = 2.47 +/- 0.11 mumol.cm-2.h-1 (n = 42)]. Both fluxes were stable for several hours. Increasing the H+ gradient across the tissue for 60 min did not change either flux. Anoxia for 45 min reversibly reduced Js----m by 65 +/ 3% (n = 20) but had no effect on Jm----s. Both fluxes were linearly related to HCO3- concentration on the buffered side, but the slope for Js----m was 3.5 times that for Jm----s. When tissues were initially set up in HEPES buffer rather than HCO3-, Js----m was 0.12 +/- 0.05 mumol.cm-2.h-1 (n = 6), which is not significantly different from zero. Replacement of Na+ by choline reduced Js----m by 40 +/- 3% (n = 11) and ouabain (1 mM) by 24 +/- 3% (n = 5). Replacement of Cl- with isethionate or K+ with Na+ for 60 min did not alter Js----m. Serosal application of DIDS (0.5 mM) reduced Js----m by 24 +/- 6% (n = 6), but SITS (0.5 mM), furosemide (1 mM), acetazolamide (0.1 mM), amiloride (1 mM), and a proton pump inhibitor (Sch 28080, 50 microM) had no effect. Mucosal application of DIDS, furosemide, and amiloride had no effect on Js----m. Serosal tetrodotoxin (1 microM) and indomethacin (28 microM) were also without effect.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1900676 TI - The cost-effectiveness of orphan drugs. PMID- 1900677 TI - Cost-effectiveness of alpha-1 antitrypsin replacement therapy in treatment of congenital chronic obstructive pulmonary disease. AB - BACKGROUND: Alpha 1-antitrypsin (AAT) replacement therapy is an expensive intervention ($20,000-$30,000 per patient annually) which may slow or arrest the progression of chronic obstructive pulmonary disease (COPD) in AAT-deficient patients. While FDA-approved, therapy efficacy is unknown. The costs and benefits of AAT replacement therapy were evaluated for patients with congenital COPD. METHODS: Epidemiological and disease cost data were taken from published sources. A discrete-time model of disease stage probability transition was developed to calculate the present-value expected cost of disease treatment, under a range of possible therapy efficacy and other parameter values. RESULTS: At an efficacy of 70 percent, the cost per life year saved with AAT replacement therapy would be between $28,000 and $72,000 (1990 US dollars), depending on patient age, sex, and smoking status. At 30 percent efficacy, the cost per life year saved range would be between $50,000 and $128,000. A controlled efficacy study would cost $53 million or less, if the true efficacy were 50 percent or better. CONCLUSIONS: With efficacy of 30 percent or higher, therapy cost-effectiveness would be comparable to other widely used medical interventions. The economic assessment methodology was used to evaluate both the therapeutic innovation and the value of additional clinical research. PMID- 1900678 TI - Effect of hospital utilization review on medical expenditures in selected diagnostic areas: an exploratory study. AB - Quarterly claims data on 43 insured groups were analyzed through multivariate techniques to explore whether the effects of hospital inpatient utilization review vary across selected broad diagnostic areas. Findings suggest that utilization review was associated with decreases in expenditures of approximately 15 percent for diagnoses within the surgical area, a lesser decrease within the mental health area, and still lesser decrease within the medical area. However, these measurements are imprecise both because of the small numbers and the aggregated diagnoses in each category. PMID- 1900680 TI - Neutrophil mechanisms. PMID- 1900679 TI - An evaluation of clinical variables in determining the need for pelvic examination in the emergency department. AB - STUDY OBJECTIVE: To evaluate the ability of multiple clinical variables to predict an increased or decreased probability of pelvic pathology, therefore determining when a pelvic examination is needed. DESIGN: Cross-sectional. SETTING: An urban emergency department. TYPE OF PARTICIPANTS: 246 female patients presenting with abdominal pain and undergoing pelvic examination. MEASUREMENTS AND MAIN RESULTS: The patients were divided into two groups. Group 1 consisted of 99 patients without pelvic pathology (40%) and group 2 consisted of 147 patients with pelvic pathology (60%). Pelvic pathology was defined as presence of infective discharge (with confirmation on wet mount/potassium hydroxide smear), presence of adnexal mass and/or tenderness, cervical motion tenderness, uterine enlargement and/or tenderness, blood in the vaginal vault, and culture report positive for Neisseria gonorrhea. The following variables achieved statistical significance (P less than .05) using a logistic regression model: history of vaginal discharge (odds ratio, 2.30 [95% confidence interval, 1.23 to 4.32]); history of dysmenorrhea/menorrhagia (4.35 [1.52 to 12.40]); right upper quadrant pain on physical examination (0.33 [0.13 to 0.85]); and left lower quadrant pain on physical examination or history (1.73 [0.94 to 3.19]). CONCLUSION: History of vaginal discharge, history of dysmenorrhea/menorrhagia, and left lower quadrant pain on physical examination act as risk variables predicting presence of pelvic disease. Right upper quadrant pain on physical examination acts as a protective variable to predict absence of pelvic disease. This information may aid the emergency physician in determining the need for a pelvic examination in women with abdominal pain. PMID- 1900681 TI - Mast cells and cell-to-cell interactions in airways. AB - Dog mastocytomas (anatomic and biochemical features comparable to normal dog and human mast cells) were used to study actions of mast cell mediators on several airway effector systems. We showed mastocytoma cell adherence to both cultured tracheal epithelial cells and tracheal tissue sections for greater than 48 h that was abolished completely by pretreatment of mast cells with proteases. This mast cell-epithelial cell adhesion-interaction reaction is probably mediated by a mast cell plasma membrane protein. Mast cell mediators stimulate short circuit current and ion flux across dog tracheal epithelia mounted in Ussing chambers. Pretreatment of epithelia with indomethacin blocks this effect, probably by inhibiting LTC4-induced activation of epithelial cyclooxygenases. Mastocytoma cells also increase secretion from cultured serous submucosal gland cells. Blockade of cyclooxygenase and lipoxygenase pathways in mastocytoma cells activated by calcium ionophore does not alter secretion of the serous cells induced by mastocytoma supernatant, but secretion induced by mastocytoma supernatant or purified mast cell chymase is markedly reduced by an inhibitor of chymase. These results suggest that mast cells can alter airway secretions not only by actions on ion flux in epithelial cells but also by actions on submucosal gland secretion; this latter action appears to be mediated by mast cell chymase. Finally, supernatants from mastocytoma cells stimulated by calcium ionophore greatly increase the sensitivity and magnitude of the contractile response of dog bronchial smooth muscle to histamine. These effects are blocked by an inhibitor of mast cell tryptase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1900682 TI - The airway epithelium and arachidonic acid 15-lipoxygenase. AB - Pulmonary epithelial cells may be primarily responsible for initiating or regulating inflammatory responses in the airways, in part by releasing chemical mediators. Among the most potent mediators of inflammation are the lipoxygenase metabolites of arachidonic acid, including the leukotrienes and other mono and dihydroxyeicosatetraenoic acids (HETES). The human airway epithelium contains significant 15-lipoxygenase activity. Although some biologic functions of 15 lipoxygenase metabolites are known, further understanding of the role of this enzyme in the airway requires localization in tissue and studies of expression, regulation, and biologic activity. Towards these aims, we purified and characterized 15-lipoxygenase from eosinophil-enriched leukocytes. First, we studied cofactors that may be involved in regulating enzymatic activity. Second, we isolated to homogeneity, for the first time, human 15-lipoxygenase. This led to the determination of the N-terminal amino acid sequence and the discovery of homology among various mammalian lipoxygenases. Finally, we utilized this structural information to isolate a cDNA that encodes for human 15-lipoxygenase. The availability of a clone will permit studies of expression and the development of antibodies for tissue localization. Further research using molecular and antibody probes is expected to increase our understanding of the biologic roles of 15-lipoxygenase in airway epithelium. PMID- 1900683 TI - Role of arachidonic acid metabolites in oleic acid induced pulmonary injury in a canine model. Effect of ketoconazole (thromboxane synthetase inhibitor). AB - This study was designed to investigate the effects of ketoconazole, a thromboxane synthetase inhibitor, on pulmonary and systemic hemodynamics and pulmonary function in experimental respiratory distress syndrome. Pulmonary artery infusion of oleic acid (PAIOA), 0.1 ml/kg, was used to cause lung injury. Ten dogs were randomized into two groups (Gps): Gp I (n = 5) acted as control, whereas Gp II (n = 5) were treated with IV ketoconazole (2.5 mg/kg bolus then 10 mg/kg/hour for 2.5 hours). Hemodynamics, extravascular lung water (EVLW), serum levels of PGE2, and TxB2 were obtained at baseline (BL) and at 30-minute intervals for 2.5 hours (T30-T150). After 30 minutes of PAIOA the mean arterial pressure (MAP) decreased significantly in both Gps (131 +/- 17 vs. 88 +/- 9 mmHg Gp 1, 119 +/- 9 vs. 79 +/ 8 mmHg Gp II, P less than 0.05); however, while MAP returned to BL values in Gp II, it remained significantly lower throughout the experimental interval in Gp I. Mean pulmonary artery pressure (MAP) was not significantly affected by PAIOA in either Gp, while pulmonary vascular resistance increased significantly from BL at T120 in Gp II. Pulmonary function measured by partial pressure of arterial O2 (PaO2) and extravascular lung water (EVLW) were significantly affected by PAIOA. There was a significant decrease in PaO2 (66 +/- 6 vs. 96 +/- 8 mmHg, Gp I and 60 +/- 7 vs. 100 +/- 6 mmHg, Gp II) as well as an increase in EVLW (604 +/- 61 vs. 135 +/- 9 ml, Gp I and 641 +/- 110 vs. 117 +/- 18 ml, Gp II) in both Gps.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1900684 TI - [Combination therapy of CPT-11, a camptothecin derivative, with various antitumor drugs against L 1210 leukemia]. AB - Antitumor effect of CPT-11 in combination with cyclophosphamide (CY), nimustin hydrochloride (AC-NU), thio-TEPA (TESPA), methotrexate (MTX), 5-fluorouracil (5 FU), cytosine arabinoside (ara-C), thioinosine (6-MPR), adriamycin (ADM), bleomycin (BLM), mitomycin C (MMC), actinomycin D (ACT-D), vincristine sulfate (VCR), etoposide (VP-16) or cisplatin (CDDP) against L 1210 murine leukemia was investigated. The combination treatment of CPT-11 with CY, ACNU, ADM, CDDP, TESPA and ACT-D showed synergistic effects and significantly prolonged the survival time of L 1210-inoculated mice compared with CPT-11 alone or antitumor drug alone. Although the combination with 5-FU, 6-MPR, VP-16, MMC or VCR had synergistic effect for some schedules exceptionally with ara-C, MTX or BLM had slight synergistic effect against L 1210. PMID- 1900685 TI - [Multihospital co-operative study of post-operative adjuvant chemotherapy in the treatment of gastric cancer-(Part 3). Comparisons between tegafur and UFT. North Kyushu Co-operative Study Group for Cancer Chemotherapy]. AB - The North Kyushu Co-operative Study Group for Cancer Chemotherapy (21 participating facilities) carried out a comparative study of post-operative adjuvant chemotherapy in the treatment of 243 patients after surgery of gastric cancer in stages II, III and IV over 27 months period starting from October 1983. The patients were divided randomly into group A (treated with 20 mg of MMC on the day of the surgery and 10 mg of MMC on the following day, and with a daily dose 600 mg of orally administered tegafur starting from two weeks after the surgery. In addition to the above treatments, patients with Stage IV were treated with 10 mg of MMC every three months starting from four weeks after the surgery) and group B (treated with MMC in a similar manner to group A, and with 600m g of UFT instead of the tegafur). Thirty-three patients (13.6%) were excluded or dropped out, and the remaining 210 cases were analyzed. No severe side effects appeared in either of the groups, and a long-term administration was safe. The five-year survival rate among the radical surgery patient was significantly higher in the UFT group compared with the tegafur group (p less than 0.05). Significantly higher survival rate in the UFT group was observed (p less than 0.05) for the cases of poorly-differentiated adenocarcinoma. From the above results it appears that an addition of UFT to the treatment with MMC is useful in post-operative adjuvant chemotherapy for gastric cancer. PMID- 1900686 TI - [Randomized controlled trial of induced hypertension chemotherapy (IHC) using angiotensin II human (TY-10721) in advanced gastric carcinoma (TY-10721 IHC Study Group Report)]. AB - A randomized controlled trial was carried out to elucidate the enhancement of chemotherapeutic effect of induced hypertension chemotherapy (IHC) using newly synthesized angiotensin II human (TY-10721) in advanced gastric carcinoma under multi-institutional cooperation. In IHC, the drugs were administered under the hypertensive state induced and maintained by the continuous infusion of TY-10721. The regimen for the trial was as follows: adriamycin (33 mg/m2, day 3), 5 fluorouracil (330 mg/m2/day through day 1 to 3, 8 to 10) and mitomycin C (5 mg/m2, day 8). It was repeated every 4 weeks. Of 67 registered cases, 62 eligible patients were randomized to either IHC arm or control arm (non-IHC) in which the drugs were administered by an ordinary i.v. injection. According to the Criteria of Japanese Society for Cancer Treatment, the response rate of IHC group was 31.3% and that of non-IHC was 6.7% with statistically significant difference (p less than 0.05; chi 2c). There were 4 CR and 6 PR in 32 eligible cases of IHC and 2 PR in 30 of non-IHC. Clinical characteristics of patients and toxicities were not different in both groups. Clinical advantage of IHC was confirmed by increase of the response rate in this trial. PMID- 1900688 TI - Rehabilitation in spinal cord disorders. 3. Comprehensive management of spinal cord injury. AB - This self-directed learning module highlights advances in the management of the person with a spinal cord deficit. Traumatic spinal cord injury is being used as the model, but the principles apply to all patients with spinal cord deficits. This article is part of the chapter on rehabilitation of spinal cord disorders for the Self-Directed Medical Knowledge Program Study Guide for practitioners and trainees in physical medicine and rehabilitation. Specifically, this section contains information regarding prehospital care, acute assessment and management, primary rehabilitation by systems, sexuality and psychosocial issues, management of pain and spasticity, functional goals, the role of functional electrical stimulation, and long-term follow-up. PMID- 1900687 TI - [Cooperative study of surgical adjuvant chemotherapy for colorectal cancer (third report): five-year results. Cooperative Study Group of Surgical Adjuvant Chemotherapy for Colorectal Cancer in Japan]. AB - A randomized controlled study was carried out by the envelope method with 491 institutions in participation across the country in order to find an optimal surgical adjuvant chemotherapy for curatively resected colorectal cancer. The schedules for drug administration were different in four districts: ACNU + Futraful (FT) group and FT alone group in the Hokkaido-Shikoku district; the same schedule groups plus untreated group in the Chubu-Kinki district; MMC+FT group, FT alone group in the Tohoku-Kanto district; and ADM+FT group and FT alone group in the Chugoku-Kyushu district. The numbers of patients admitted to this study were 2,450 cases with colon cancer and 2,456 cases met the evaluation criteria of this study. The 5-year survival rate on the whole did not differ from combination therapy to single drug therapy in either colon cancer or rectal cancer, but in Dukes C rectal cancer the five-year survival rate tended to be higher with the combination therapies. In n2 (+) or a2(s) rectal cancer in particular, combination therapies with MMC and FT and with ADM and FT achieved significantly higher five-year survival rate, and the rate of local recurrence was significantly lower with ADM+FT. PMID- 1900689 TI - Effects of lobenzarit disodium on human endothelial cells. Lobenzarit disodium inhibits proliferative response, HLA-DR antigen expression, and T cell adherence toward endothelial cells. AB - The therapeutic action of lobenzarit disodium (CCA) on the function of endothelial cells (EC) isolated from human umbilical cord veins was investigated. CCA suppressed 3H-thymidine incorporation into EC in a dose-dependent manner. Significant inhibition was detected at a concentration of 50 micrograms/ml. The expression of HLA-DR antigen on the surface of EC was increased when EC were cultured with recombinant interferon-gamma (rIFN gamma). Treatment of EC with either IFN gamma or interleukin-1 enhanced the adhesion of T cells to EC. The kinetics of HLA-DR antigen expression by EC cultured with IFN gamma was different from the kinetics of T cell-EC adhesion, however. Neither anti-HLA-DR nor anti HLA-ABC monoclonal antibody inhibited T cell binding to EC monolayers. CCA suppressed the expression of HLA-DR antigen by EC cultured with rIFN gamma. In an EC monolayer adhesion assay, CCA also inhibited T cell adhesion to EC in the presence of either IFN gamma or interleukin-1. Significant inhibition was observed at a CCA concentration of 10 micrograms/ml, a level that is easily attainable in serum. These results suggest that CCA may suppress rheumatoid synovitis by reducing the angiogenesis and emigration of chronic inflammatory cells from the blood into the synovium. PMID- 1900690 TI - Restricted diversity of the variable region nucleotide sequences of the heavy and light chains of a human rheumatoid factor. AB - The complete nucleotide sequences of the variable region genes of the heavy and light polypeptide chains of a human monoclonal rheumatoid factor (RF) produced from a human-mouse heterohybridoma were determined. The antibody, designated YES8c, contained V kappa III, J kappa 2, VH1, JH4, and a D gene segment of 9 amino acids. The nucleotide sequences and the deduced amino acid sequences of the light chain variable region were remarkably homologous (97-98%) to previously described RF of the Wa idiotypic family (PAY, GLO, CUR, FLO, and GAR) and to that of a V kappa III germline gene (Humkv325). The YES8c heavy chain variable region gene was most closely related to the VH1 gene of the restricted human fetal repertoire, designated 51p1, and also to 3 rearranged VH1 genes that were recently isolated from patients with chronic lymphocytic leukemia. These results suggest that variable region genes of RFs are highly conserved and that YES8c VH, as well as V kappa, may be identical to heavy and light chains expressed during early B cell development. PMID- 1900691 TI - Time out of mind. PMID- 1900692 TI - Bond strength of repaired glass ionomer core materials. AB - Chelon Silver (C), Ketac-Silver Aplicap (K), Miracle Mix (M) silver-reinforced glass ionomers, and Valiant PH.D were evaluated as in vitro repair materials for cores. The core materials were placed in a 6 x 3 mm mold and stored at 37 degrees C at 100% RH for 24 hours. The cores were roughened with a coarse diamond. Five samples were conditioned (T) with Dentin Conditioner for 20 seconds, whereas another 5 samples were untreated (U). The cores were then repaired with C, K and M and subsequently tested after additional storage for 24 hours. Bond strength (MN/m2) was measured in tension using an inverted cone bond test at a crosshead speed of 0.05 cm/min. Mean bond strengths (S.D.) for the three repair materials when averaged over the three glass ionomer cores were: K, 5.0 (1.2); M, 3.4 (1.2) and C, 2.7 (1.5) for condition U; and M, 4.2 (1.1); K, 3.4 (1.2); and C, 3.1 (1.0) for condition T, where M, K and C were the repair materials. The Tukey intervals at the 95% level were 0.7 among materials and 0.5 between treatments. Bond strength of repaired amalgam was only successful with M, 0.9 MN/m2. Bond strengths to untreated silver-reinforced glass ionomer cores were higher with K used as a repair material. PMID- 1900693 TI - Shear bond strength of dental amalgam bonded to dentin. AB - The objective of this study was to determine the shear bond strength of dental amalgam bonded to dentin with adhesives. Four groups of 15 permanent posterior teeth were used in this study. The occlusal enamel of the teeth was removed to produce a flat dentin surface. The teeth were embedded in phenolic rings with acrylic resin. Vinyl polysiloxane ring molds 4 mm thick with 4.5 mm circular openings were attached to the exposed dentin surface. Adhesives applied to the dentin surfaces prior to amalgam placement and condensation included: Amalgambond, a 4-META/TBB-MMA, HEMA based system (A), Panavia EX, a modified phosphate ester of Bis-GMA luting system (P), and Ketac-Cem, a glass ionomer luting cement (K). A dentin bonding agent and composite resin restoration system (Scotchbond 2/Silux Plus) was included for comparison. The specimens were stored in 37 degrees C water for 7 days prior to testing. Shear bond tests were done in an Instron machine at a crosshead speed of 0.02 inches per minute. The data were analyzed by ANOVA at 5% level of significance. The differences in shear bond strengths of the four test groups were not statistically significant (P = 0.115). Fracture patterns of the bonded amalgams, examined by SEM, were adhesive in appearance for Groups A and K and cohesive for Group P. PMID- 1900694 TI - Epidermal toxicity of disinfectants. AB - The purpose of the present study was to investigate the capacity of various disinfectant chemicals to cause epithelial toxicity with repeated exposure. The abdominal area of 3-month old, experimental ICR/CD-1 mice was initially shaved, denuded with a depilatory agent and allowed to rest for 24 hours. Commercial preparations of iodophors, bleach, synthetic phenols, phenolic/alcohols, and glutaraldehydes were then sprayed onto the exposed abdominal tissue 8 times/day (0.8 ml spray) for 2 consecutive days. The applied disinfectant was allowed to dry between procedures. In comparison to controls sprayed with distilled water, each disinfectant stimulated some degree of epidermal changes. Resultant multiple brownish lesions showed local thickening and hardening. Histologically, epidermal changes ranged from mild hypertrophy to extensive epithelial erosion. A few inflammatory cells were occasionally detected in the epithelium. When present, dermal reactions ranged from a mild inflammation to focal areas of collagen degeneration. The results indicated that iodophors stimulated the mildest reactions, followed by the synthetic phenol preparations, bleach, phenolic/alcohols, and glutaraldehyde sprays. Similar assays using glutaraldehyde immersion sterilants/disinfectants produced marked tissue destruction. PMID- 1900695 TI - Politics, public policy, and the development of community mental retardation services in the United States. AB - Data emanating from the community services component of the Third National Study of Public Spending for Mental Retardation and Developmental Disabilities was analyzed. An empirical model of community services spending in the states was tested in a hierarchical regression analysis using cumulative community services fiscal effort in the states across 1977-1988 as the dependent variable. Strength of consumer advocacy organizations in the states coupled with states' historical orientations toward the adoption of policies promoting racial equality were highly significant predictors of state-by-state variance in community spending patterns. The implications of this and other findings emerging from the national study were discussed. PMID- 1900696 TI - Current and future trends in state-operated mental retardation institutions in the United States. AB - Results of a national study of state-operated institutional care in the United States were presented. The relations among census reduction, staffing level, and resident cost were explored. Resident cost escalated dramatically in recent years, primarily because staffing levels in the states remained relatively stable, whereas the institutional census continued to decline. Econometric projections suggest that by the year 2000, the institutional census will fall below 55,000 persons, cost per resident will rise to more than $113,000 per year, and 28 to 51 institutions will close. PMID- 1900697 TI - A method for sequencing polymerase chain reaction products can be used to sequence Bacillus subtilis "miniprep" plasmid DNA. AB - Several methods for sequencing double-stranded plasmid DNA isolated from E. coli have been described. These methods are usually not effective when used to sequence plasmid DNA isolated from Bacillus subtilis. In the course of developing a simplified version of a previously published protocol for polymerase chain reaction product sequencing, it was found that this protocol could be used for sequencing plasmid DNA isolated from Bacillus subtilis. PMID- 1900698 TI - Spontaneous contrast in the pericardial sac caused by gas-forming organisms. AB - Purulent pericarditis is a life-threatening disease associated with a variety of microorganisms. The case presented herein has unusual manifestations of contrast echoes on two-dimensional echocardiography. To our knowledge, this is the first reported case of pericarditis caused by gas-forming group D Streptococcus and Klebsiella pneumoniae with pyopericardium, resulting in contrast echoes on the two-dimensional echocardiographic image. PMID- 1900700 TI - HIV/AIDS. US faces care crisis. PMID- 1900699 TI - The isolation and culture of DHBV-infected embryo and duckling hepatocytes and the effect of aflatoxin B1 or irradiation on these cells. AB - The preparation of primary cultures of control and DHBV-infected duck hepatocytes from embryos and young ducklings is described. Cultures of both embryo and duckling hepatocytes secreted duck serum proteins. Cultures of hepatocytes established from ducklings maintained initial morphology for up to 3 weeks in culture and also exhibited high levels of metabolism of aflatoxin B1. Embryonic cell cultures rapidly lost ability to metabolise AFB1 and became overgrown by spindle-shaped cells. Both embryo and duckling cell cultures secreted infective DHBV, and had intracellular replicative forms of the virus. No integration of the virus into the duck genome was observed, and attempts to induce viral integration in the duckling hepatocytes using irradiation and aflatoxin B1 toxicity were unsuccessful. The results of the study lend further support to the suggestion that the rarity of liver cancer in DHBV-infected experimental ducks is related to an innate resistance of the hepatocytes to develop DHBV-DNA integration. Another possibility may be related to the lower oncogenic potential of the DHBV strain used for the study. However DHBV infected duckling hepatocytes would appear to offer a suitable material for studying viral replication and mechanisms of aflatoxin B1 toxicity during prolonged cell culture. PMID- 1900701 TI - Redirection 'essential' to tackle AIDS in Africa. PMID- 1900702 TI - Co-trimoxazole in low doses 'prevents PCP'. PMID- 1900704 TI - When the troops return. PMID- 1900703 TI - Can nursing lead care? PMID- 1900705 TI - Scottish excellence. A community of innovators. PMID- 1900706 TI - Prison nursing. Entering a very different world. PMID- 1900707 TI - Blood and body fluid precautions. AB - The well-publicised dangers of contracting infection from blood-borne viruses make an awareness of comprehensive protective measures for self and others an imperative for nurses. Sarah Hart reviews the precautions nurses should take when dealing with contaminated blood and other body fluids, and lays emphasis on the need for all nurses, regardless of the particular area in which they work, to adopt and promote safe practices. PMID- 1900708 TI - Accountability in delivering care. AB - In the penultimate part of this series on issues in ward management facing charge nurses. George Castledine concentrates on the issue of accountability. The immensely powerful position of the charge nurse as arbitrator and co-ordinator of all health care given to the patient demands that helshe exercises this power responsibly and positively; hence, the crucial importance of accountability. The author explores this concept and also those of advocacy and conscientious objection. He concludes by suggesting that the ultimate area of accountability in nursing is the individual conscience of the practitioner and that in this may lie the key to the setting and maintenance of high standards of care. PMID- 1900709 TI - The new breed. PMID- 1900710 TI - Standard setting in paediatrics. AB - Dissatisfaction with pre-admission procedures for day-case paediatric admissions led nurses in Gwent to adopt the Donabedian model of standard setting to express the quality of service they wished to provide. The outcome has been so successful, claim the authors, that plans have been made to review all pre admission procedures in the same way. PMID- 1900711 TI - Troublespots in quality assurance. AB - Despite an upsurge in awareness of quality assurance programmes and standard setting at all levels of the National Health Service, few nurses are as yet experienced in planning and implementing quality assurance systems. Janet Whelan's article is designed to point out possible problem areas that nurses may encounter on moving into this field, and offers advice on how to negotiate them. PMID- 1900712 TI - The significance of urine testing. AB - The examination of urine to discover the nature, causes and prognoses of diseases was one of the earliest procedures to be adopted by physicians. Today, urine testing remains an important aid in diagnosing and monitoring disease and treatment, and in helping to provide clues to a patient's health and wellbeing. June Thompson discusses the value of this nursing procedure. PMID- 1900713 TI - Points of view. PMID- 1900714 TI - Your uninformed consent. PMID- 1900715 TI - Visit at your peril. PMID- 1900716 TI - Meagre fare for nurses' pay. PMID- 1900717 TI - Psychiatric roundup. PMID- 1900718 TI - Directing your career. PMID- 1900719 TI - AIDS threat to Edinburgh young. PMID- 1900720 TI - Culture of bovine granulosa cells in a chemically defined serum-free medium: the effect of insulin and fibronectin on the response to FSH. AB - Granulosa cells from fully differentiated bovine follicles were cultured in serum free medium for 4 days. At the end of culture, the number of viable cells was low (10-15% of cells plated on day one) and only progesterone secretion responded to FSH. Insulin increased the number of viable cells at the end of culture (ED50 # 70 ng/ml) and stimulated progesterone secretion (ED50 # 50 ng/ml); the secretion of oestradiol-17 beta over basal value was evident only for concentrations of 1000 and 10,000 ng/ml. FSH acted synergistically with insulin to modify steroid secretion. In the presence of 50 ng/ml of insulin, dose-response studies indicated that secretion of progesterone was maximal at 10 ng/ml of FSH and plateaud thereafter, while oestradiol output peaked at 2 ng/ml of FSH, decreasing at higher concentrations. When cells were seeded in wells precoated with fibronectin, a comparison with cells cultured on plastic showed an increase (30 40%) in the number of viable cells at the end of culture and in oestradiol secretion but a decrease in progesterone output. These results indicate that granulosa cells from large bovine follicles, cultured in a serum-free medium containing insulin, maintain their steroidogenic potency for at least 4 days. Moreover, they show that oestradiol and progesterone synthesis are differentially sensitive to FSH concentrations and that fibronectin increases oestradiol secretion in response to FSH. PMID- 1900721 TI - Cancrum oris-like lesions. AB - Cancrum oris is predominantly seen in children in underdeveloped countries where widespread malnutrition, dehydration and epidemic infections are present. In the western world, it is sometimes found in immunosuppressed adults with predisposing conditions such as leukaemia and infection associated with malnutrition. Early diagnosis and an intensive therapeutic approach are the key to a favourable prognosis of noma-like necro-ulcerative lesions. The prognosis is significantly improved if the predisposing condition can be removed. Two cases are presented and the treatment is discussed. PMID- 1900722 TI - Calcium-dependent transient potassium outward current in the marine ciliate Euplotes vannus. AB - In the marine hypotrichous ciliate Euplotes vannus, the transient K+ outward current, IK fast, was studied by use of a single-microelectrode voltage-clamp equipment. Activation and inactivation kinetics, and steady-state inactivation are comparable to the properties of A-currents. Not typical for this type of current is its insensitivity to either 4-AP or 3,4-AP and its Ca2+ dependence which was derived from its inhibition by either extracellular Cd2+, La3+, D-600, or by intracellular BAPTA. Actual amplitudes of IK fast were obtained from a composite current, by subtraction of early parts of a slowly activating K+ current, IK slow, and of the early, transient Ca2+ inward current, ICa fast, that is typical for ciliates. IK fast counteracts ICa fast during the first milliseconds after onset of depolarization such that the composite current is purely outward directed. PMID- 1900723 TI - Upper GI abscess formation and intramural hemorrhage: sequelae from possible gastric perforation. AB - The definition of an abscess is, "a localized collection of pus caused by suppuration in a tissue, organ or confined space." Pyogenic bacteria that invade the tissue are responsible for this inflammatory response. The following case study demonstrates such a response via an unusual presentation of upper gastrointestinal bleeding. PMID- 1900724 TI - Medical assessment and treatment of chronic epilepsy. PMID- 1900725 TI - Epilepsy related to traumatic extradural haematomas. PMID- 1900726 TI - Radiation induced extraskeletal osteosarcoma. PMID- 1900727 TI - Dosimetry of electron backscatter at mandibular reconstruction in megavoltage photon beam. PMID- 1900728 TI - Corticobasal degeneration. A unique pattern of regional cortical oxygen hypometabolism and striatal fluorodopa uptake demonstrated by positron emission tomography. AB - Corticobasal degeneration presents with an asymmetric akinetic-rigid syndrome, apraxia and combinations of supranuclear gaze palsy, myoclonus, and an alien limb. Six patients aged 59-77 yrs, diagnosed on clinical criteria as having corticobasal degeneration, have been studied with positron emission tomography using tracers of dopamine storage capacity and oxygen metabolism. Striatal 18F-6 fluorodopa uptake was reduced in an asymmetric pattern, caudate and putamen being involved in all cases. Uptake into medial frontal cortex was also impaired. Regional cortical oxygen metabolism was most significantly depressed in the superior and posterior temporal, inferior parietal, and occipital associated cortices. Within the frontal lobe, the hypometabolism was chiefly posterior. This unique combination of regional hypometabolism and disruption of the nigrostriatal system is discussed in relation to the clinical features of the disease and is compared with reported findings in other disorders of cognition and movement. PMID- 1900729 TI - [Localization and modulation of galactosyltransferase during in vitro proliferation of a human ovarian adenocarcinoma cell line]. AB - A cell line, IGROV1, originating from a human ovarian cancer, releases a galactosyltransferase activity in its culture medium during proliferation. The proliferating IGROV1 cells appear as two populations: some cells grow in floating clusters whereas the greater part of them adhere to the culture substrate. The study of galactose transfer by intact cells onto an exogenous glycoprotein acceptor (ovomucoid) shows the presence of surface-associated galactosyltransferase onto the two cellular sub-populations. Opposite to intracellular activity, surface-associated and released galactosyltransferase activities depend on cellular adhesion and proliferation. PMID- 1900730 TI - [Lipid profiles of breast cancer cell lines: proton nuclear magnetic resonance spectroscopy]. AB - Nuclear magnetic resonance spectroscopy was performed on breast cancer cell lines MCF-7, MDA-MB231 and T47D. Proton spectra showed discrepancies of lipid quantity in the different lines. The high resolution lines of lipids were not as intense in the membrane preparations. These results show the potential of NMR spectroscopy to study the involvement of membrane lipids in proliferation, metastasis or drug resistance process. PMID- 1900731 TI - [Detection of homologous oncogene sequences in the genome of Plasmodium falciparum]. AB - Homologous sequences of the acute RNA tumor virus oncogenes have been found to be highly conserved within vertebrates, insects and yeasts. In the present work, seven different oncogene DNA sequences have been used as probes to search for homologous sequences in the DNA of the protozoan Plasmodium falciparum. Both the v-fms v-Ha ras probes hybridized P. falciparum DNA. The oncogene study will allow an understanding of the biology of the parasite and particularly the host parasite relationships which allow P. falciparum to develop, keeping the established harmony between the parasite and his host. PMID- 1900732 TI - [Reexpression of the embryonic form of NCAM in the rat hippocampus after status epilepticus induced by neurotoxic agent]. AB - The neural cell adhesion molecule (NCAM) is known to take part in the cohesion of cellular interactions through a homophilic binding mechanism. During development, NCAM shifts from an embryonic polysialic acid-rich form to a poorer adult one. This conversion reflects a loss of plasticity to the benefit of more stability. We have shown here an inverse process, namely the reexpression of the embryonic form of NCAM in adult rats following a status epilepticus induced through systemic administration of kainic acid. PMID- 1900733 TI - [Improvement of an in vitro transcription method in nuclei isolated from heart myocytes from control and hemodynamically overloaded rats]. AB - The expression of genes crucial for different cardiac functions changes during ontogenic development and during hypertrophy due to hemodynamic overload. To determine if these changes are transcriptional or post-transcriptional, we describe here an optimized method to analyze in vitro the transcriptional activity of nuclei isolated from control and hemodynamically overloaded hearts of 23-day-old rats. Similar results were obtained with both types of hearts: (1) 3 to 6 million nuclei were isolated per gram of ventricular tissue; (2) nuclear incorporation of UTP32P increases with time, plateaus after about 10 to 20 min. and attains an average of 0.17 cpm per nucleus; (3) alpha-amanitin decreases total incorporation by 56%; (4) the sizes of the majority of transcribed RNA are between 0.2 and 4 kb, although a significant fraction of high molecular weight transcripts are also seen (between 4 and 6 kb). All this indicates that mRNAs are transcribed to a significant extent, suggesting that it is now possible, given appropriate nucleotide probes, to analyze the transcription of any given gene during cardiac growth. PMID- 1900734 TI - Cost-effectiveness analysis of mass screening for breast cancer in Japan. AB - The official Japanese recommendation for breast cancer screening is physical examination by a physician, in contrast to US recommendations of mammography. In this analysis of breast cancer screening, the authors used Japanese data in a cost-effectiveness model to compare the following five strategies: (1) no screening (N); (2) physical examination alone (PE); (3) mammography (MG); (4) PE followed by MG if PE findings were abnormal (PE----MG); and (5) PE combined with MG for all screened women (PE + MG). None of these programs would save medical expenditures. The total discounted net costs per patient (in US dollars) were as follows: N, +54; PE, +412; MG, +517; PE----MG, +340; and PE + MG, +731. The number of years of life saved per cohort of 100,000 asymptomatic Japanese women would range from 708 (PE----MG) to 3724 (PG + MG). The additional cost of each strategy (compared with N) per additional year of life would be +49,700 for PE, +40,400 for PE----MG, +14,300 for MG, and +18,000 for PE + MG. The least costly screening option (PE----MG) does not have the lowest cost per additional year of life saved (MG does). MG would be preferable to the current Japanese recommendation of PE alone. PMID- 1900737 TI - Chemopreventive action of mace (Myristica fragrans, Houtt) on DMBA-induced papillomagenesis in the skin of mice. AB - The present paper reports the chemopreventive property of mace (aril covering the seed of Myristica fragrans) on DMBA-induced papillomagenesis in the skin of male Swiss albino mice. When a single topical application of DMBA (150 micrograms in 100 microliters of acetone) was followed, 2 weeks later, by repeated applications of croton oil (1% in acetone, three times/week) skin papillomas appeared in 100% animals and the average tumors per tumor-bearing animal was 5.67. On the other hand, when animals receiving similar treatments were put on a diet containing 1% mace during the periinitiational phase of tumorigenesis, the skin papilloma incidence was reduced to 50% and the average tumor per tumor-bearing mouse was only 1.75. This decline in papilloma was significant (P less than 0.05). PMID- 1900736 TI - Modulatory effect of crocetin on aflatoxin B1 cytotoxicity and DNA adduct formation in C3H10T1/2 fibroblast cell. AB - Crocetin is a carotenoid isolated from the seeds of Cape jasmine (Gardenia jasminoides). The cytotoxicity and DNA-adduct formation of rat microsome activated aflatoxin B1 (AFB1) in the C3H10T1/2 cells were significantly inhibited by pretreatment of crocetin. Most significant inhibition was found at the time of 9 h after crocetin pretreatment. Under these experimental conditions, consistent elevation in the cytosolic glutathione (GSH) levels and the activities of GSH S transferase (GST) and GSH-peroxidase (GSH-Px) were observed. Crocetin treatment also resulted in a decrease in AFB1-DNA adduct formation in vitro, while no effect of crocetin on the formation of AFB1-8,9-oxide in vitro system was detected as measured by the Trisdiol method. From these results, we suggested that the protective effect of crocetin on the AFB1-cytotoxicity in C3H10T1/2 cells might be due to the cellular defense mechanisms that elevated the cytosol GSH and the activities of GST and GSH-Px. PMID- 1900738 TI - Influence of diet and calorie restriction on the initiation and promotion of skin carcinogenesis in the SENCAR mouse model. AB - Diets were restricted to 60% of the intake of the control mice by feeding less diet (total diet restriction, TDR) or by feeding fewer calories from fat and carbohydrate (calorie restriction, CR) during the initiation or promotion phases of skin tumorigenesis in female SENCAR mice. Skin cancer was initiated by topical treatment with 10 nmol of 7,12-dimethylbenzanthracene in acetone and promoted by twice weekly treatments with 12-O-tetradecanoylphorbol-13-acetate in acetone for 20 wk. Dietary restriction preceding and during 7,12-dimethylbenzanthracene treatment did not influence skin papilloma or carcinoma yield. Papilloma incidence and the number of papillomas per effective mouse were reduced in mice restricted by both TDR and CR protocols during and following promotion with 12-O tetradecanoylphorbol-13-acetate. Papilloma size was reduced at experimental wk 16 and 20 in both TDR and CR groups fed these diet regimens during promotion. However, by wk 28 and 32, papilloma sizes were similar in the control and TDR groups, and smaller papillomas were observed only in the CR group. The average carcinoma latency was extended by 26% in the groups restricted during promotion, and incidence was reduced in both groups. The reduction, however, was statistically significant only in the CR group. Body weight gain was reduced during the times when dietary restriction was enforced, and in a short-term study, both restricted diet treatments reduced the percentage of carcass protein. PMID- 1900739 TI - Chinese hamster ovary cell lines resistant to mitomycin C under aerobic but not hypoxic conditions are deficient in DT-diaphorase. AB - We have previously reported the isolation of CHO cell lines resistant to mitomycin C under aerobic conditions of drug exposure. Here it is reported that these cell lines have the same response to mitomycin C under hypoxic conditions as do controls. The cells are shown to have lower levels of DT-diaphorase activity than controls, but similar levels of activity of NADPH:cytochrome c reductase, another enzyme involved in the metabolism of mitomycin C. Evidence for molecular defects in the DT-diaphorase gene or gene transcript is presented for the deficient cell lines. The consequences of this DT-diaphorase deficiency is further explored by testing the toxicity of menadione, an established enzyme substrate. The isolation of CHO cell lines deficient in DT-diaphorase activity and resistant to mitomycin C under aerobic but not hypoxic conditions suggests that mitomycin C reduction by this enzyme has a significant impact on cytotoxicity under aerobic but not hypoxic conditions. Similarly, DT-diaphorase metabolism of menadione does not appear to have a significant impact on cytotoxicity in CHO cells. PMID- 1900735 TI - Microbiology of airway disease in patients with cystic fibrosis. AB - Individuals with cystic fibrosis have abbreviated life spans primarily due to chronic airway infection. A limited number of types of organisms are responsible for these infections, with Staphylococcus aureus and Pseudomonas aeruginosa being of primary importance. In the pre-antibiotic era, greater than 90% of deaths due to infection were caused by S. aureus and death usually occurred in the first 2 years of life. With the advent of effective antistaphylococcal therapy, life spans increased and P. aeruginosa became the pathogen of primary importance. P. aeruginosa isolates recovered from patients with cystic fibrosis have a unique phenotypic characteristic referred to as "mucoid." The mucoid phenotype is due to the production of a mucoid exopolysaccharide. A mucoid exopolysaccharide is believed to play a central role in the establishment of chronic pseudomonal lung infection in these patients. A third organism, Pseudomonas cepacia, has recently been detected in the airways of older patients with cystic fibrosis and is associated with increased mortality. The virulence of P. cepacia is not understood, but the organism is extremely refractory to antimicrobial therapy. Other bacteria, including Haemophilus influenzae and members of the family Enterobacteriaceae, appear to play a secondary role in airway infection. Aspergillus fumigatus is the most important fungal agent causing allergic bronchopulmonary disease. The role of viruses has only recently been examined. At least in some patients with cystic fibrosis, respiratory syncytial virus may be important in predisposing to subsequent bacterial infections. PMID- 1900740 TI - Human T-lymphocytes synthesize and secrete a protease resistant proteoglycan in a delayed, serum-dependent response to concanavalin A. AB - In the presence of radioactive precursors, the addition of Concanavalin A (Con A) to cultures of mononuclear cells (MC) from human blood resulted in marked accumulation in the medium of a protease-resistant proteoglycan (PG) with chondroitin sulfate (CS) chains of an average molecular weight of 28 KDa. This PG was shown to be elaborated primarily by T-cells. The addition of serum was necessary for maximal stimulation with Con A and under these conditions PG accumulation in the medium rose slowly during the first few days of culture and much more rapidly between days 6-8. PMID- 1900741 TI - Endocytosis without clathrin (a minireview). PMID- 1900742 TI - Interpretations of five monoclonal immunoassays of lutropin and follitropin: effects of normalization with WHO standard. AB - Five mono(oligo)clonal immunometric assays for lutropin (LH) and follitropin (FSH)--bioMerieux, IRE-Medgenix, Serono Diagnostics, Diagnostics Products Corp. (DPC), and LKB--were evaluated in comparison with two polyclonal RIAs (DPC and Amersham). Detection limits varied from 0.04 to 0.32 int. unit/L and 0.06 to 0.86 int. unit/L for LH and FSH, respectively. Intra- and interassay precision (CV) at three concentrations varied from 2.0% to 29.8%, showing that not all kits tested gave acceptable results, especially for LH. Linearity and parallelism were acceptable, except for the DPC FSH kit and the bioMerieux LH kit. High-dose "hook" effects were seen in some kits at LH concentrations of 250 int. units/L, but not in the FSH kits up to concentrations of 350 int. units/L. Reagents in some kits cross-reacted with choriogonadotropin. The clinical validity of the assays was tested in 25 pre- and 25 postmenopausal healthy women and in 66 patients with polycystic ovary disease. In contrast to FSH, LH values varied significantly not only between polyclonal and monoclonal assays but also between the various monoclonal assays, despite the fact that all manufacturers state that their kits are calibrated on the same standards: WHO International Reference Preparation (IRP) 68/40 for LH and 78/549 for FSH. We normalized the results by using new WHO standards: IRP 80/552 for LH and IRP 83/575 for FSH. This decreased significantly the between-kit differences in LH results for individuals. The much used LH/FSH ratio greater than 3 for diagnosing patients with polycystic ovary disease is not valid when monoclonal assays are used, and is kit-dependent. However, using the normalized results yields a "new" LH/FSH ratio, which is kit independent and differs significantly between patients and healthy subjects. PMID- 1900743 TI - Blood lymphocyte proliferation, cytokine secretion and appearance of T cells with activation surface markers in cultures with Helicobacter pylori. Comparison of the responses of subjects with and without antibodies to H. pylori. AB - A whole inactivated H. pylori bacterium preparation was found to stimulate blood mononuclear cells from both antibody-positive and antibody-negative subjects, but the antibody-positive subjects tended to have lower proliferation responses. The present study was designed to characterize T cell activation further by measuring several components of the response. Eighty-seven subjects (80 dyspeptic patients and seven healthy persons from the laboratory staff) with or without antibodies to H. pylori were studied by measuring the DNA synthesis induced by several H. pylori concentrations (1-23 micrograms/ml) and the control stimulants PPD, tetanus toxoid and pokeweed mitogen (PWM). H. pylori-induced secretion of interleukin-2 (IL-2), tumour necrosis factor-alpha (TNF-alpha), interleukin-4 (IL 4), soluble CD8 and IL-2 receptor (IL-2R) molecules and H. pylori- and PPD induced appearances of IL-2R+ and HLA-DR+ T cells were measured in a smaller number of subjects. H. pylori-induced DNA synthesis was again lower in the antibody/bacterium-positive subjects, while no differences between the two groups were found in cultures stimulated by unrelated antigens or PWM. Soluble IL-2R and TNF-alpha were detectable in cultures with H. pylori from all subjects, while the amount of IL-2 did not differ from that in the background culture. No differences were found in the amounts of IL-2 or soluble IL-2R between the antibody-positive and negative subjects; while the former tended to secrete more soluble CD8 molecules, a difference which was significant with the smaller H. pylori concentration used (P less than 0.01). The numbers of HLA-DR+ and IL-2R+ T cells increased in cultures with H. pylori or PPD from all the subjects, the majority of both cells having the CD4 phenotype. Numbers of DR+ and IL-2R+ T cells were similar in the cultures of the antibody-positive and negative subjects, but the respective CD8 subsets were increased in the former. The confirmed decrease in proliferation in the antibody-positive subjects does not seem to be connected with lower IL-2/IL-2R responses but may involve CD8 cell activation. PMID- 1900746 TI - Cold defects in in-111 labeled leukocyte imaging of osteomyelitis in the axial skeleton. AB - Use of In-111 oxine labeled leukocytes in the detection of osteomyelitis of the peripheral skeleton usually presents few problems. However, the diagnosis of osteomyelitis is more difficult in marrow-bearing areas because uptake of indium is normal. Sixty-one In-111 labeled leukocyte scans, that had been performed to exclude osteomyelitis of the axial skeleton, pelvis, and proximal long bones, were reviewed. Eight cold defects were identified at sites of suspected osteomyelitis. Five of these were surgically proven osteomyelitis. Nineteen percent of all cases of osteomyelitis in these areas (5 of 26) presented as cold defects. This incidence of osteomyelitis presenting as cold defects is higher than previously reported. Therefore, the possibility of osteomyelitis should be strongly considered when a cold defect is identified in red marrow areas. PMID- 1900744 TI - Clonotypic analysis of human antibodies specific for Neisseria meningitidis polysaccharides A and C in adults. AB - Serum antibodies to the capsular polysaccharides A and C (PSA and PSC) of N. meningitidis in healthy adults before and after vaccination with the sole polysaccharides were analysed by isoelectric focusing (IEF). Before vaccination, 49% and 28% had naturally acquired antibodies against PSA and PSC, respectively, whereas 18 days after vaccine administration 84% and 91%, respectively, showed a detectable spectrotypic pattern. Oligoclonality appeared to be the main feature of naturally acquired and vaccine-induced antibodies for both polysaccharides. In all subjects the anti-PSA response, showing dominant bands at the same pH position, was more homogeneous than anti-PSC one. Most subjects with naturally acquired antibodies (25 out of 38 for PSA and 20 out of 22 for PSC) showed a spectrotypic pattern after vaccination, similar to that observed before vaccination (any differences were just related to band intensity), suggesting that PSA and PSC are able to recruit the same B cell clones previously primed with a T-dependent form of the antigen, i.e. the whole bacterium. However, in one third of subjects with naturally acquired anti-PSA antibodies, the appearance of new alkaline bands after vaccination was observed. Furthermore, in subjects with absence of detectable natural antibodies, the vaccine-induced antibody response started in correspondence of alkaline pH areas, subsequently extending to neutral and acidic areas. Therefore, it may be hypothesized that alkaline antibody secreting B cell clones are the first to be recruited. The final spectrotype in these subjects was similar to that observed in subjects with naturally acquired antibodies. This observation, together with the above reported data, allow us to conclude that natural (T-dependent pathway) and vaccine (T-independent pathway) immunization induce the expression of the same antibody repertoire, for both meningococcal PSA and PSC. PMID- 1900747 TI - The Chinese hamster cell mutant V-H4 is homologous to Fanconi anemia (complementation group A). AB - V-H4, a mitomycin C (MMC)-sensitive Chinese hamster cell mutant, is phenotypically very similar to Fanconi anemia (FA) cells. Genetic complementation analysis shows that V-H4 belongs to the same complementation group as FA group A cells. Proliferating hybrid cell lines obtained after fusion of V-H4 with normal or FA group B cells show an increased resistance to MMC. Absence of complementation was noted in V-H4 x FA group A hybrid cell lines. This was shown not to be due to the absence of a specific human chromosome. The V-H4 mutant represents the first rodent mutant that is genotypically similar to FA complementation group A cells. PMID- 1900748 TI - [Choice of adhesive as a function of degree of mineralization of the dentin surface]. PMID- 1900745 TI - Modulation of Mycobacterium avium growth in vivo by cytokines: involvement of tumour necrosis factor in resistance to atypical mycobacteria. AB - The protective mechanisms associated with resistance to atypical mycobacteria infections are not clear. In an effort to broaden our understanding of the mechanisms involved, susceptible mice were infected with a virulent strain of M. avium and various treatments were applied so as to modify the course of the disease. Treatment with an antiserum against tumour necrosis factor-alpha (TNF alpha) significantly enhanced the experimental infection, as judged by enumeration of colony-forming units (CFU) in the spleens and livers of infected mice, suggesting a role for TNF-alpha in resistance to M. avium. In other sets of experiments, recombinant cytokines were directly infused into infected mice. Infusion of recombinant interferon-gamma (IFN-gamma) did not modify the experimental infection significantly, and infusion of interleukin-2 was also without effect. Injection of TNF-alpha enhanced resistance in susceptible animals, as seen by a reduction in the viable bacilli recovered from the spleens and livers. In a final set of experiments, we demonstrate that combinations of cytokines may induce strong resistance against M. avium, namely injection of 1 micrograms of interleukin-1 alpha and 1 micrograms of TNF-alpha at 5-day intervals which was seen to eradicate M. avium in both spleens and livers of susceptible BALB/c mice. Overall, our results suggest that induction of protection against M. avium by treatment with cytokines may be feasible, and that TNF-alpha may be a pivotal molecule in resistance to M. avium. PMID- 1900749 TI - [Serum ABO immune antibodies in 1944 pregnant women]. AB - The ABO+ Rh blood groups and serum anti- A and anti -B anti bodies were examined in 1944 pregnant women. The results showed that 475 cases (24.4%) were positive for serum immune antibodies resulting in ABO incompatibility, and in 68 (3.4%) newborns haemolytic disease (HDN) occurred. The incidence of ABO blood group incompatibility increased with the increase of maternal serum immune antibody titer, the difference between different titers was significant (chi 2 = 4.13, P less than 0.05). Pregnant women with a high titer of serum immune antibody greater than 1:64 should be followed up regularly and those greater than 1:128 should be treated immediately. The relationship between positive serum immune antibody and blood group was discussed. We consider it is important to do maternal serum immune antibodies examination for antenatal care. PMID- 1900750 TI - [Attitude of caregivers to suicide patients. An empirical study of nurses]. PMID- 1900751 TI - [Multi-morbidity in old age]. PMID- 1900752 TI - [Care of chronically ill patients. Psychological aspects]. PMID- 1900753 TI - [The patient with rheumatism as chronically ill patient]. PMID- 1900754 TI - [Multiple sclerosis--a disease with which one can live]. PMID- 1900755 TI - [The cancer patient--a chronically ill patient. The care of seriously ill patients from the nursing viewpoint]. PMID- 1900756 TI - [The care of oncologic patients]. PMID- 1900757 TI - [Psychosocial aspects in the care of patients treated with cytostatic drugs]. PMID- 1900759 TI - [The significance of chronic illness for the child and its family]. PMID- 1900758 TI - [Chronic disease--perspective and management approach of social work in the hospital]. PMID- 1900760 TI - [Chronically ill--due to an accident]. PMID- 1900761 TI - [Nursing standards--on sense and necessity]. PMID- 1900762 TI - [Medico-psychological management of chronically ill patients]. PMID- 1900763 TI - [Materials for supervision and practice guidance (I). Development, testing and process-supporting evaluation of a components model in the supervision of hospital personnel in the continuing education course "Fundamentals of psychological health demands" at the Oldenburg University]. PMID- 1900764 TI - [Nursing care, monitoring and early mobilization of patients with myocardial infarct]. PMID- 1900765 TI - [Psychosomatic aspects of coronary heart disease. Findings, experiences and practical consequences]. PMID- 1900766 TI - [The treatment of coronary heart disease using balloon dilatation]. PMID- 1900767 TI - [Coronary artery bypass operations. The surgical treatment of coronary heart disease]. PMID- 1900768 TI - [Surgical therapy of arrhythmias]. PMID- 1900769 TI - [Congenital coronary artery anomalies]. PMID- 1900770 TI - [Mucocutaneous lymph node syndrome (Kawasaki syndrome) from the cardiological viewpoint]. PMID- 1900773 TI - [Invasive diagnosis of coronary heart disease]. PMID- 1900772 TI - [The Swan-Ganz catheter: nursing role in catheter insertion and patient monitoring]. PMID- 1900771 TI - [Safety for staff and patients in the hospital area]. PMID- 1900774 TI - [The treatment of acute myocardial infarct in the hospital]. PMID- 1900775 TI - Hypersecretion of follicle-stimulating hormone (FSH) after ovariectomy of hypophysectomized, pituitary-grafted rats: implications for local regulatory control of FSH. AB - Previous observations have shown that a portion of the acute (less than 12 h) FSH hypersecretion after ovariectomy (OVX) is LHRH independent, thereby suggesting that mechanisms governing the acute FSH hypersecretory response to OVX may reside largely within the anterior pituitary gland. Accordingly, the present studies were conducted to determine whether acute OVX-induced FSH hypersecretion can be elicited in an animal model in which the anterior pituitary gland is isolated from diencephalic chemical signals, and if so, whether the hypersecretion could be abated by the FSH-suppressing protein, follistatin. Adult female rats hypophysectomized (H) 1 week earlier received anterior pituitary grafts (H/G) (one to three glands per rat) under the kidney capsule. In order to increase ovarian secretion of negative feedback effectors substances (i.e. estrogen, inhibin), some H/G rats were injected sc with 30 IU PMSG 4-6 days after receiving pituitary transplants, whereas other rats were given the saline vehicle. Two days later (0830 h), a blood sample was obtained via an indwelling atrial catheter inserted the previous day. H/G rats given saline or PMSG then were further subdivided and either castrated or sham castrated. Additional blood samples were obtained from the catheter, and trunk blood was collected from decapitated rats 24 h after OVX for measurement of serum estradiol and PRL levels. For comparison, H rats not receiving renal pituitary transplants were subdivided into similar experimental groups as the H/G rats. Blood samples were also obtained after sham OVX or OVX of pituitary-intact, 4-day cycling rats on diestrous day 1. Ovariectomy of PMSG-treated H rats receiving either one or three pituitary allografts resulted in a significant (P less than 0.01) increase in serum FSH levels by 12 h after OVX followed by a 2- to 3-fold increase in FSH levels by 24 h relative to either the pre-OVX FSH levels measured in this group or the FSH levels measured in PMSG-treated H/G rats 24 h after sham OVX. In contrast, OVX of saline-treated H/G rats failed to elicit FSH hypersecretion. Similarly, FSH hypersecretion was not observed after OVX of saline- or PMSG-treated H rats. Whereas serum LH levels were increased 24 h after OVX of diestrous rats, no such increases were detected 24 h after OVX of any H or H/G rats. In an additional experiment, H rats receiving two pituitary allografts were treated with PMSG and subsequently castrated. Twenty-four hours later, rats were injected iv with either 60 micrograms purified porcine follistatin or saline.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1900776 TI - Differential regulation of thyroid hormone receptor messenger ribonucleic acid levels by thyrotropin-releasing hormone. AB - In addition to its well known actions in stimulating TSH and PRL synthesis and secretion, TRH has been shown to decrease the concentration of thyroid hormone receptors (TRs) in GH4C1 cells as measured by nuclear thyroid hormone (T3) binding. In the present study we have investigated the effects of TRH on the levels of mRNA encoding the different forms of TR, TR beta-1, TR beta-2, and TR alpha-1 as well as that of the non-T3-binding variant, c-erbA alpha-2. GH3 cells were incubated with 100 nM TRH in the presence or absence of 1 nM T3 for 48 h, and mRNA levels were determined by Northern blot analysis. Results revealed that there is differential regulation of the individual TRs by TRH at the pretranslational level. The mRNA for the pituitary-specific form of TR, TR beta 2, was down-regulated by 60% by TRH in GH3 cells, while that of its alternative splice product, TR beta-1, was unchanged. A modest change was observed in TR alpha-1 mRNA levels, which were down-regulated by 20%; there was no change in c erbA alpha-2 mRNA levels. Levels of nuclear T3 binding were assessed under the same conditions, and 100 nM TRH was found to decrease binding by 40% from 0.78 to 0.46 fmol/micrograms DNA. A similar change in nuclear T3 binding was seen after incubation with 1 nM T3. The effect of TRH on the GH mRNA response to T3 was investigated. In the absence of TRH there was a 4-fold induction of GH mRNA after incubation with 1 nM T3. In the presence of 100 nM TRH, no significant induction in GH mRNA by T3 was seen, indicating that T3 responsiveness as well as receptor concentration are diminished by TRH under these conditions. PMID- 1900777 TI - Lack of effect of melatonin on myometrial electromyographic activity in the pregnant sheep at 138-142 days gestation (term = 147 days gestation). AB - A 24-h rhythm has been demonstrated in fetal and maternal melatonin plasma concentrations in pregnant sheep in the last third of gestation. Melatonin in the maternal circulation can cross the placenta and is the major source of melatonin in the fetal circulation. Melatonin has been postulated to act as a prostaglandin (PG) synthetase inhibitor in the uterus. PG synthetase inhibitors decrease myometrial contractility. To assess transplacental passage of melatonin and potential influences of melatonin on uterine contractility, we infused melatonin continuously into the maternal jugular vein in seven pregnant sheep at 138-142 days gestation (term in our instrumented animals is 147 days gestation) at three infusion rates for successive 1-h periods during the late morning to late afternoon. There was no change in the total time during which the myometrium was active, as indicated by myometrial electromyographic activity or the myometrial contracture frequency during the 3 h before and after melatonin infusions and for each hour of the infusions. The MCR for melatonin in the ewe was 4128 +/- 410 ml/min (mean +/- SE; n = 7; weight, 50-70 kg). The resting maternal to fetal melatonin concentration ratio was 0.8; this ratio was maintained at 2.28 during melatonin infusion to the ewe at a wide range of maternal melatonin concentrations. Melatonin concentrations in the range of 3-200 times normal had no effect on the maternal plasma PGF2 alpha metabolite concentration, but caused a 40.4% fall in fetal plasma PGE2 (P less than 0.05). We conclude that changes in maternal and fetal plasma melatonin concentrations within the physiological range observed throughout the day do not alter myometrial contractility, but do alter fetal PGs. PMID- 1900779 TI - An inhibitory effect of transferrin on differentiation of rat granulosa cells in vitro. AB - The effects of human transferrin (TRF) on granulosa cell function were examined using serum-free cultures of rat granulosa cells obtained from immature, diethylstilbestrol-treated rats. The results show that TRF had dose- and time dependent inhibitory effects on FSH-induced inhibin and progesterone production with the half-maximal inhibitory dose of 6.1-6.3 micrograms/ml. The inhibitory effect of TRF on FSH-induced inhibin and progesterone production was not reversed by removing TRF and changing medium after 48 h of treatment. TRF also inhibited insulin- and insulin-like growth factor-I (IGF-I)-induced inhibin production in a dose-dependent manner. TRF did not inhibit forskolin- and 8-bromo-cAMP-induced progesterone production but did inhibit inhibin production induced by these agents. TRF had no effect on basal production of inhibin and progesterone. On the other hand, high concentrations of insulin and cortisol completely counteracted the inhibitory effect of TRF on FSH-induced progesterone production but only partially counteracted the inhibitory effect of TRF on FSH-induced inhibin production. Our data suggest that: 1) TRF may be an important negative modulator of the stimulatory actions of FSH or IGF-I and other factors acting on granulosa cells; 2) the inhibitory effects of TRF require the presence of FSH or other factors such as IGF-I or insulin, which facilitate granulosa cell differentiation; and 3) different mechanisms are involved in the modulating effects of TRF on inhibin and progesterone production. PMID- 1900778 TI - Heterologous down-modulation of luteinizing hormone receptors by prolactin: a flow cytometry study. AB - Although the binding, internalization, and regulation of LH, PRL, and their respective receptors have been extensively studied, it is not known whether the receptors are coordinately regulated. Using double labeling experiments, we have previously shown that receptor-bound LH and PRL can be colocalized in identical endosomes of granulosa cells. We hypothesize that high levels of PRL may induce a heterologous down-modulation of LH receptors, consequently reducing ovarian responsiveness to further gonadotropin stimulation. In this study we used a novel procedure to enrich endosomes containing internalized PRL and to determine whether unoccupied LH receptors were cointernalized in granulosa cells. Porcine granulosa cells were obtained from medium-sized (3-5 mm) follicles and cultured for 4 days in the presence of FSH. Fluorescein isothiocyanate-labeled PRL (FITC PRL) was used as a ligand to induce internalization of PRL receptors and as a marker to label endosomes. Granulosa cells were incubated with FITC-PRL at either 4 or 37 C for various times. At the end of the incubation, cells were trypsinized to remove surface receptors and then homogenized. The postnuclear fraction containing endosomes and other subcellular organelles was sorted using a FACStar Plus cell sorter. Results from 14 separate sorting experiments showed that 1) FITC-PRL-treated cells exhibited a sorting pattern distinct from that of FITC-BSA treated or untreated cells; 2) excess unlabeled PRL partially shifted the sorting profile to one similar to that in controls; 3) the differences in sorting profiles were not due to free FITC; and 4) using this method, it was possible to isolate FITC-PRL-containing endosomes that were virtually devoid of other contaminating subcellular particles. Fluorescently positive (FITC-PRL-containing) organelles were collected and assayed for LH receptors using [125I]hCG as a tracer. When the cells were incubated with FITC-PRL at 37 C for 3 h, the number of available LH receptors (as determined by [125I]hCG binding) was 37% higher in particles containing FITC-PRL than in those devoid of FITC-PRL. If the cells were allowed to preincubate with FITC-PRL at 4 C for 10-16 h before raising the temperature to 37 C, the number of available LH receptors in FITC-PRL-containing endosomes was about 7-fold higher than that in FITC-negative endosomes. Results from this study suggest that PRL not only induces internalization of its own receptor, but also causes down-modulation of unoccupied LH receptors.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1900780 TI - Sertoli cell function varies along the seminiferous tubule: the proportion and response of transferrin secretors differ between stage-associated tubule segments. AB - Recent studies from our laboratory demonstrated clearly that only a portion of all Sertoli cells secrete transferrin (TF). These findings raised the possibility that differences in the functional type of Sertoli cells from one location to another may account in part for the stage-related variation in TF release along the seminiferous tubule. In order to address this, Sertoli cells derived from tubule segments corresponding to stages III-V, VII, IX-XI, and XIII of the seminiferous epithelial cycle were subjected to reverse hemolytic plaque assays to determine whether the proportion of TF cells present in those segments were similar or different. We found 21.4 +/- 1.8%, 20.3 +/- 2.0%, 48.3 +/- 2.5%, and 49.2 +/- 3.2% of all cells secreted TF in III-V, VII, IX-XI, and XIII staged segments, respectively. Results obtained from immunocytochemical staining of cells from different sections agreed well with those obtained with plaque assays, indicating that we had detected most, if not all, TF cells in these cultures. In additional experiments, we found that cultured cells from stage III-V and VII responded to FSH or isoproterenol with a large increase in the rate of TF plaque formation, whereas cells from IX-XI and XIII segments appeared to be unaffected. In contrast, bovine fibroblast growth factor caused a marked increase in the rate of TF plaque formation with IX-XI cells and only a slight increase with cells from III-V staged segments. Thus, the manner in which Sertoli cells respond to several modulatory agents appears not only to be stage-dependent, but also to be specific to the agent in question. When taken together, our observations demonstrate that cultured TF secretors obtained from different staged segments of the seminiferous tubule differ in proportion and responsiveness. These findings, when viewed in light of reports of a constant number of Sertoli cells along the seminiferous tubule, suggest that Sertoli cells may acquire and lose the ability to secrete TF or respond to modulation as the seminiferous cycle progresses. PMID- 1900781 TI - Oxytocin secretion by bovine granulosa cells: effects of stage of follicular development, gonadotropins, and coculture with theca interna. AB - Oxytocin (OT) has been detected in ruminant preovulatory follicles. Bovine granulosa cells express the oxytocin/neurophysin I (OT/NP-I) gene and secrete OT in vitro. The objective of this study was to determine the developmental pattern of OT secretion by bovine follicle cells as they differentiate during the follicular phase and the preovulatory follicle approaches ovulation. Holstein heifers were injected with prostaglandin F2 alpha in midluteal phase to induce luteal regression and initiate a follicular phase. The ovary bearing the preovulatory follicle was obtained by ovariectomy early in the follicular phase, in midfollicular phase, or late in the follicular phase, after the LH/FSH surge (n = 4 heifers per group). Theca interna and granulosa cells were isolated and cultured for 5 days, individually or in coculture, in defined or serum-containing medium and with or without LH (300 ng/ml) or FSH (300 ng/ml). Media were collected and replaced completely every 24 h, and OT secreted into the media was measured by RIA. Granulosa cells isolated at all three time points during the follicular phase secreted measurable amounts of OT. However, total OT secretion by granulosa cells isolated after the LH/FSH surge was 18.9-fold (defined medium) to 64.8-fold (serum-containing medium) higher than OT secretion by granulosa cells isolated early in the follicular phase, and 14.6-fold (defined medium) to 170-fold (serum-containing medium) higher than OT secretion by granulosa cells isolated in midfollicular phase. Granulosa cells isolated before the LH/FSH surge responded to the addition of LH or FSH to the culture medium with an increase in OT secretion. Cocultures of granulosa cells and theca interna isolated before the LH surge secreted more OT than cultures of granulosa cells alone. When cells were isolated early in the follicular phase the effect of coculture was more than additive, but the effect of coculture was only additive when follicles were obtained in midfollicular phase. OT secretion by granulosa cells isolated after the LH/FSH surge was not affected by gonadotropins or by coculture with theca interna. In contrast to results for granulosa cells, theca interna secreted only small and variable amounts of OT, and responses to LH were inconsistent. These findings suggest that OT detected in cultures of theca interna may be produced by small and variable numbers of granulosa cells contaminating the theca interna preparation.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1900782 TI - In vivo biological validation and biophysical modeling of the sensitivity and positive accuracy of endocrine peak detection. II. The follicle-stimulating hormone pulse signal. AB - Despite interest in the in vivo control of gonadotropin release, valid assessment of the physiological regulation of the pulsatile secretion of the gonadotropin FSH has been hampered by the uncertain validity and reliability of available FSH peak detection algorithms. Difficulties in identifying FSH peaks accurately are believed to arise in part because of the slow metabolic clearance of this glycoprotein hormone. Here, we have used two complementary strategies to test the validity of FSH pulse detection. First, by means of a computer-assisted mathematical model for simulating episodic hormone secretion, we evaluated the effects of various putative FSH secretory pulse amplitudes and half-lives on the sensitivity and positive accuracy of peak detection. Secondly, we used an in vivo primate animal model, in which presumptively true FSH pulses were evaluated independently by continuous electrophysiological monitoring of mediobasal hypothalamic multiunit activity. These two approaches allowed us to define optimal pulse analysis parameters that yield maximal sensitivity and positive accuracy for detecting FSH peaks in synthetic and biological time series. We found (as predicted intuitively) that increasing half-times of hormone disappearance decrease both the sensitivity and positive accuracy of peak detection for any given peak detection thresholds and hormone secretory amplitudes. However, adequately sampled episodic FSH time series could be analyzed for FSH pulsatility by an appropriately constrained, objective computerized algorithm with reasonable (less than 10-15%) false negative and false positive errors, such that resultant sensitivity and positive accuracy exceed 85-90%. Of interest, computer simulations and the in vivo animal model exhibited similar discriminative capabilities. We conclude that increasing half times of hormone (e.g. FSH) removal do impair hormone peak detection sensitivity and positive accuracy. Nevertheless, gonadotropin time series can be analyzed for FSH pulsatility in a valid manner with adequately constrained false negative and false positive error rates. PMID- 1900783 TI - Reevaluation of the electrophysiological actions of thyrotropin-releasing hormone in a rat pituitary cell line (GH3). AB - The electrophysiological actions of TRH were examined in the clonal pituitary cell line GH3 with the use of the perforated patch variation of the standard whole cell patch-clamp technique. The action of TRH on spontaneously spiking cells was to cause a brief hyperpolarization (first phase action), followed by a period during which action potential behavior was significantly modified (second phase action). The modifications during second phase action included a reduction in the slope of the up-stroke, a reduced peak potential, an increase in duration, and a depolarizing shift of the after-hyperpolarization. The modification of voltage- and calcium-dependent conductances that underlie these changes were investigated in voltage clamp experiments. During first phase action TRH was found to increase calcium-dependent potassium current. During second phase action TRH was found to significantly reduce the L-type calcium current (35%), with no alteration in the T-type calcium current. The second phase action of TRH on calcium-dependent potassium conductance was complex. First, a decrease was observed. This was followed by an increase that did not become fully manifest until after TRH was washed from the cell. TRH caused no change in voltage dependent potassium current. These results indicate that the second phase action of TRH on action potential behavior in GH3 cells is mediated by a reduction in L type calcium current and alterations in the behavior of calcium-dependent potassium currents, but not through changes in voltage-dependent potassium currents. PMID- 1900785 TI - Inhibition of pituitary gonadotropin secretion by the gonadotropin-releasing hormone antagonist antide. II. Development of an in vitro bioassay for characterization of pharmacokinetics and pharmacodynamics of antide in circulation. AB - Previous data from this laboratory revealed a rapid and unexpectedly long inhibition of pituitary gonadotropin secretion in ovariectomized monkeys after a single high dose injection of the GnRH antagonist antide. This extended action of antide may correlate with an extended presence of antide in the peripheral circulation. We have reported on use of a RRA for antide in serum; however, during such a prolonged presence in the body, the possibility of catabolic loss of biological activity remained to be analyzed. In the present study, we have developed an in vitro pituitary cell bioassay for antide to investigate the pharmacokinetics and possible mechanism(s) contributory to its long action. Dispersed anterior pituitary cells from adult female rats were plated (48 h; 5 x 10(5) cells/well), washed, and incubated with 0.024-6 ng antide for 24 h. Media were removed, and cells were washed twice and then incubated with GnRH (1 x 10( 8) M) plus antide standards or serum samples for 4 h. Before antide injection into long term ovariectomized monkeys, peripheral GnRH antagonist levels were undetectable. One day after a single injection (3.0 mg/kg, sc, in 50% propylene glycol-water), the level of antide was 31 +/- 13 ng/ml (n = 3). Thereafter, antide levels declined slowly and were still detectable (greater than 1.4 ng/ml) in two of three monkeys 31 days after injection. After iv administration (3.0 mg/kg; n = 2), peripheral antide levels followed a similar pharmacokinetic profile and declined slowly. Detectable antide concentrations were still present 36 days after single iv injection in both monkeys. The circulating half-lives of antide were 1.7 and 14.5 days for the first and second phases, respectively. Peripheral LH levels were suppressed to the limits of detectability within 1 day and slowly recovered to pretreatment levels within 30 +/- 5 days after sc or iv antide treatment. The ratio of bioactive antide to antide levels measured by RRA was similar throughout the study (chi = 1.24 +/- 0.09; range, 0.40-2.22), although there was a trend toward an increased B/R ratio at the end of the study. In summary, we have developed an in vitro bioassay using cultured rat pituitary cells to measure biologically active antide concentrations in peripheral circulation after sc and iv treatments. The prolonged action of antide on pituitary gonadotropin secretion in vivo is apparently due to the continued presence of biologically active antide in circulation after a single injection.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1900784 TI - Inhibition of pituitary gonadotropin secretion by the gonadotropin-releasing hormone antagonist antide. I. In vitro studies on mechanism of action. AB - The GnRH antagonist antide is among the most promising "third generation" compounds available for clinical evaluation. In primates, antide manifests prolonged (several weeks) and reversible inhibition of pituitary gonadotropin secretion after a single high dose injection. In the present study, we have examined the effects of antide on pituitary gonadotropin secretion in vitro. Dispersed anterior pituitary cells from adult female rats were plated (48 h; 5 x 10(5) cells/well), washed, and exposed to increasing concentrations of antide for up to 48 h. Media were removed, and cells were washed twice and then incubated with GnRH (1 x 10(-8) M) plus antide for 4 h. Media and cell lysates were assayed for LH/FSH by RIA. Antide had no effect on basal LH/FSH secretion at any dose tested (10(-6)-10(-12) M). In contrast, GnRH-stimulated LH/FSH secretion was inhibited by this GnRH antagonist in a dose- and time-dependent manner. When incubated simultaneously, antide blocked GnRH-stimulated gonadotropin secretion, with a maximal effect at 10(-6) M (ED50, 10(-7) M). Preincubation of pituitary cells with antide for 6-48 h before GnRH exposure shifted the dose-response curve to the left; the maximally effective dose was 10(-8) M; the ED50 was 10(-10) M antide after 48-h preincubation. Intracellular LH/FSH levels increased concomitant with the decrease in secreted gonadotropins. Total LH/FSH levels (secreted plus cell content) remained unchanged. The inhibition of LH secretion by antide was specific for GnRH-stimulated gonadotropin secretion; antide had no effect on K(+)-stimulated LH secretion. Moreover, antide had little or no residual effect on LH secretion; full recovery of GnRH responsiveness in vitro occurred within 4 h after removal of antide. Lineweaver-Burke analysis of antide inhibition of GnRH-stimulated LH secretion indicated that antide is a direct competitor of GnRH at the level of the pituitary GnRH receptor. In summary, antide is a pure antagonist of GnRH stimulation of gonadotropin secretion; no agonistic actions of antide were manifest in vitro. Moreover, antide has no apparent noxious or toxic effect on pituitary cells in culture; the actions of antide are immediately reversible upon removal of antide from pituitary gonadotropes. We conclude that the long term inhibition of gonadotropin secretion by antide in vivo is not due to deleterious effects of this compound at the level of the pituitary gonadotrope. PMID- 1900786 TI - An inhibitory effects of interleukin-1a on basal gonadotropin release in the ovariectomized rhesus monkey: reversal by a corticotropin-releasing factor antagonist. AB - Interleukin-1 (IL-1), an important component of the immune system, has recently been shown to influence the release of several hormones in the rodent. In this paper, the effectiveness of IL-1a in modulating basal gonadotropin secretion as well as cortisol release in the primate has been investigated. Eight adult ovariectomized rhesus monkeys were given a 30-min intracerebroventricular infusion of physiological saline (n = 5), various doses of IL-1a (17 micrograms n = 5; 8.5 micrograms; n = 3; 4.2 micrograms n = 5; and 2.1 micrograms n = 4) or IL 1a plus a CRF antagonist (n = 5). LH and FSH concentrations were measured at 15 min intervals during the 3-h preinfusion baseline control and the 5-h postinfusion period, while cortisol concentrations were determined at 45-min intervals. While LH concentrations remained unchanged in the monkeys receiving saline only, they decreased significantly after the 30-min IL-1a infusion. By hour 5 after IL-1a administration, mean (+/- SE) hourly areas under the LH curves (expressed as a percentage of preinfusion baseline) were 27.7% +/- 7.3 (17 micrograms IL-1a), 31.9% +/- 8.4 (8.5 micrograms), 33.3% +/- 5.5 (4.2 micrograms), and 39% +/- 4.0 (2.1 micrograms) (P less than 0.05 vs. morning control). FSH concentrations were also significantly decreased after IL-1a, 17 micrograms: by hour 5, they were 67.4% +/- 5.0 of baseline control. While cortisol concentrations decreased thoughout the experiment in the animals receiving saline, they increased with all IL-1a doses: overall mean (+/- SE) postinfusion concentrations were 21.8 +/- 1.1 (saline), 49.5 +/- 2.2 (IL-1a, 17 micrograms), 35.1 +/- 1.9 (8.5 micrograms), 45.7 +/- 1.5 (4.2 micrograms), and 39.5 +/- 1.5 (2.1 micrograms) micrograms/dl (P less than 0.05 IL-1a vs. saline). Concomitant infusion of the CRF antagonist, [D-Phe12, NLE 21,38caMe LEU37] CRF (12-41), (120-360 micrograms), prevented the IL-1a induced LH inhibition. By hour 5, areas under LH curves were 33.5% +/- 1.7 for IL-1a alone and 99.2% +/- 4.2 (NS vs. saline) for IL-1a + CRF antagonist. The CRF antagonist also blocked the ability of IL-1a to increase cortisol secretion: mean cortisol concentrations were 28.6 +/- 1.4 micrograms/dl (NS vs. saline). The results clearly indicate that the cytokine IL-1a inhibits pulsatile LH and FSH secretion in the ovariectomized rhesus monkey and demonstrate that this inhibition is causally related to the activation of CRF by this cytokine.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1900787 TI - 1,25-Dihydroxycholecalciferol enhances both the bombesin-induced transient in intracellular free Ca2+ and the bombesin-induced secretion of prolactin in GH4C1 pituitary cells. AB - In GH4C1 rat pituitary cells, 1,25-dihydroxycholecalciferol [1,25-(OH)2D3] enhances both the synthesis of PRL and the TRH-induced transient increase in cytosolic free calcium ( [Ca2+]i). In the present report we investigated whether 1,25-(OH)2D3 could enhance the effect of the tetradecapeptide bombesin (BBS) in GH4C1 cells. Pretreatment of the cells with 1 nM 1,25-(OH)2D3 for 24 h enhanced the BBS-induced transient increase in [Ca2+]i compared to that in control cells, while having no significant effect on the plateau phase of [Ca2+]i. Addition of the Ca2+ channel blocker nimodipine or chelating extracellular Ca2+ with EGTA did not abolish the enhancement of the BBS response in 1,25-(OH)2D3-pretreated cells. Furthermore, the BBS-induced efflux of 45Ca2+ from cells preequilibrated with 45Ca2+ was larger in cells treated with 1,25-(OH)2D3. Incubating GH4C1 cells with 1,25-(OH)2D3 alone or in combination with BBS for up to 72 h did not stimulate synthesis of PRL. However, the BBS-induced secretion of PRL was enhanced in cells pretreated with 1,25-(OH)2D3 for 24 h compared with that in vehicle-treated control cells. The effect of 1,25-(OH)2D3 on BBS-induced secretion was dose dependent, with 10(-11) M 1,25-(OH)2D3 enhancing the stimulated secretion of PRL. We conclude that in GH4C1 cells, pretreatment with 1,25-(OH)2D3 enhances the BBS induced transient increase in [Ca2+]i. This effect may be due to a modulation of the availability of sequestered intracellular Ca2+ and/or membrane Ca2+ conductance. Furthermore, pretreatment with 1,25-(OH)2D3 enhanced secretion of PRL stimulated by BBS. The enhanced transient increase in [Ca2+]i may be the factor inducing the enhanced BBS-induced secretion of PRL. PMID- 1900788 TI - Metabolism of arachidonic acid by rat adrenal glomerulosa cells: synthesis of hydroxyeicosatetraenoic acids and epoxyeicosatrienoic acids. AB - Metabolites of arachidonic acid have been implicated in the regulation of aldosterone release. To form a basis for further investigations in this area, the present study has isolated and identified the metabolites formed from exogenous arachidonic acid by adrenal zona glomerulosa cells and characterized the effects of several inhibitors on the synthesis of these eicosanoids. Rat adrenal glomerulosa cells metabolized exogenous [14C]arachidonic acid to products comigrating with the prostaglandins (PGs), hydroxyeicosatatraenoic acids (HETEs) and epoxyeicosatrienoic acids (EETs). The metabolites were found in the cells and the incubation media; however, none of the metabolites were found esterified to cellular lipids. The major metabolites were identified as 6-keto PGF1 alpha, PGE2, PGF2 alpha, PGD2, 12(S)-HETE, 15(S)-HETE, 14,15-EET, 11,12-EET, 8,9-EET, and 5,6-EET. The identities of the HETEs and EETs were confirmed by gas chromatography/mass spectrometry. There was no evidence for the synthesis of leukotrienes. The cyclooxygenase inhibitor, indomethacin, the lipoxygenase inhibitors, nordihydroguaiaretic acid, baicalein and AA861, and the combined cyclooxygenase/lipoxygenase inhibitors, BW755C and eicosatetrayenoic acid, inhibited the formation of the [14C]PGs, the [14C]HETEs, and the [14C]EETs. Metyrapone and clotrimazole, inhibitors of cytochrome P450, increased the synthesis of [14C]PGs and [14C]HETEs and reduced the synthesis of [14C] EETs. Superoxide dismutase did not alter arachidonic acid metabolism. In contrast, arachidonic acid metabolism was increased in cells pretreated with catalase. These data indicate that adrenal glomerulosa cells metabolize exogenous arachidonic acid to a number of oxygenated metabolites including PGs, HETEs, and EETs. From studies with inhibitors, the EETs appear to be synthesized by a cytochrome P450 epoxygenase and the HETEs by lipoxygenases. PMID- 1900789 TI - Intractable epilepsy and structural lesions of the brain: mapping, resection strategies, and seizure outcome. AB - Forty-seven patients with structural brain lesions on neuroimaging studies and partial epilepsy intractable to medical therapy were studied. Prolonged noninvasive interictal and ictal EEG recording was performed, followed by more focused mapping using chronically implanted subdural electrode plates. Surgical procedures included lesion biopsy, maximal lesion excision, and/or resection of zones of epileptogenesis depending on accessibility and involvement of speech or other functional areas. The epileptogenic zone involved exclusively the region adjacent to the structural lesion in 11 patients. It extended beyond the lesion in 18 patients. Eighteen other patients had remote noncontiguous zones of epileptogenesis. Postoperative control of epilepsy was accomplished in 17 of 18 patients (94%) with complete lesion excision regardless of extent of seizure focus excision. Postoperative control of epilepsy was accomplished in 5 of 6 patients (83%) with incomplete lesion excision but complete seizure focus excision and in 12 of 23 patients (52%) with incomplete lesion excision and incomplete focus excision. The extent of lesion resection was strongly associated with surgical outcome either in itself (p less than 0.003), or in combination with focus excision. Focus resection was marginally associated with surgical outcome as a dichotomous variable (p = 0.048) and showed a trend toward significance (p = 0.07) only as a three-level outcome variable. We conclude that structural lesions are associated with zones of epileptogenesis in neighboring and remote areas of the brain. Maximum resection of the lesion offers the best chance at controlling intractable epilepsy; however, seizure control is achieved in many patients by carefully planned subtotal resection of lesions or foci.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1900790 TI - Exacerbation of partial seizures and onset of nonepileptic myoclonus with carbamazepine. AB - A child had two to three generalized tonic-clonic (GTC) seizures per week unresponsive to phenobarbital (PB) and valproate (VPA). Interictal EEG demonstrated left occipital spikes. When carbamazepine (CBZ) therapy was started, he developed very frequent (4-6/day) complex partial seizures (CPS) characterized on ictal EEG by focal right temporal lobe discharges. The seizure exacerbation, which was associated with development of nonepileptic, multifocal myoclonus, resolved 24 h after CBZ was discontinued. The exacerbation occurred with therapeutic CBZ serum levels, but may have been related to the toxic levels of carbamazepine-10, 11-epoxide (CBZE). PMID- 1900791 TI - Clinical effects of allopurinol on intractable epilepsy. AB - We studied the clinical efficacy of allopurinol as add-on therapy in 31 patients with intractable epilepsy. When administered for a short time, allopurinol was effective in 17 patients (55%); 8 were seizure-free, 8 had 75% decrease in seizure frequency, and 1 had greater than 50% decrease. Allopurinol was most effective in patients with localization-related epilepsy, especially in secondarily generalized tonic-clonic seizures. Allopurinol was not as effective in patients with Lennox syndrome or West syndrome, or in severe myoclonic epilepsy in infants. When allopurinol was administered greater than 1 year, its initial effectiveness continued in 8 of 14 patients who exhibited initial improvement. In 2 of the remaining 6 patients, the initial improvement disappeared during the course of treatment but control was regained by increasing the dosage of allopurinol. Mild side effects were observed in 4 patients (13%): drowsiness in 3 and abdominal pain in 1. Allopurinol may be a useful antiepileptic drug (AED), and a double-blind placebo-controlled trial should be performed. PMID- 1900792 TI - Cytosolic acidification leads to Ca2+ mobilization from intracellular stores in single and populational parietal cells and platelets. AB - Regulatory relationship and gain control between cytosolic free Ca2+ concentration (Cai) and cytosolic pH (pHi) were evaluated by two different cell types, gastric parietal cells, and blood platelets. Studies were carried out in both single cells and populations of cells, using Ca2(+)-indicative probe fura-2 (1-(2-(5'-carboxyoxazol-2'-yl)-6-aminobenzofuran-5-oxy)-2-(2 '-amino-5'- methylphenoxy)ethane-N,N,N',N'-tetraacetic acid) and pH-indicative probe BCECF (2',7'-bis(carboxyethyl)carboxyfluorescein). Stimulation of single and populational parietal cells and platelets with gastrin and thrombin, respectively, resulted in an increase in Cai. In both populational cell types, an initial change in pHi during agonist stimulation occurred almost simultaneously with the mobilization of Ca2+; an initial transient decrease in pHi was followed by a slower increase in pHi above the prestimulation level. When populational platelets were preloaded with the Ca2+ chelator BAPTA (1,2-bis(o aminophenoxy)ethane-N,N,N',N'-tetraacetic acid), the thrombin-induced initial large increase in Cai was apparently inhibited, whereas the pHi decrease induced by thrombin was not altered. This suggests that the initial Cai change is not a prerequisite for the pHi change. The effect of pHi on Cai was examined next. In both single and populational cell types, application of the K(+)-H+ ionophore nigericin, which induced a transient decrease in pHi, led to the release of Ca2+ from intracellular stores. In single parietal cells double-labeled with fura-2 and BCECF, a temporal decrease in pHi preceded the rise in Cai after stimulation with nigericin. A decrease in pHi and an increase in Cai occurred at 1.5 and 4 s, respectively. In single parietal cells, replacement of medium Na+ with N-methyl-D glucamine (NMG+), which also induced a decrease in pHi, resulted in repetitive Ca2+ spike oscillations. The source of Ca2+ utilized for the Ca2+ oscillation that was induced by NMG+ originated from the agonist-sensitive pool. Thus, several maneuvers, which were capable of decreasing pHi, led to an increase in Cai. Cytosolic acidification may be a part of the trigger for Ca2+ mobilization from intracellular stores in both parietal cells and platelets. PMID- 1900793 TI - Life with CO or CO2 and H2 as a source of carbon and energy. AB - An account is presented of the recent discovery of a pathway of growth by bacteria in which CO or CO2 and H2 are sources of carbon and energy. The Calvin cycle and subsequently other cycles were discovered in the 1950s, and in each the initial reaction of CO2 involved adding CO2 to an organic compound formed during the cyclic pathway (for example, CO2 and ribulose diphosphate). Studies were initiated in the 1950s with the thermophylic anaerobic organism Clostridium thermoaceticum, which Barker and Kamen had found fixed CO2 in both carbons of acetate during fermentation of glucose. The pathway of acetyl-CoA biosynthesis differs from all others in that two CO2 are combined with coenzyme A (CoASH) forming acetyl CoA, which then serves as the source of carbon for growth. This mechanism is designated the acetyl CoA pathway and some have called it the Wood pathway. A unique feature is the role of the enzyme carbon monoxide dehydrogenase (CODH), which catalyzes the conversion of CoASH, CO, and a methyl group to acetyl CoA, the final step of the pathway. The pathway involves the reduction of CO2 to formate, which then combines with tetrahydrofolate (THF) to form formyl THF. It in turn is reduced to CH3-THF. The methyl is then transferred to the cobalt on a corrinoid-containing enzyme. From there the methyl is transferred to CODH, and CO and CoASH bind with the enzyme at separate sites. Acetyl CoA is then synthesized. CODH would more properly be called carbon monoxide dehydrogenase-acetyl CoA synthase as it catalyzes oxidation of CO to CO2 and the synthesis of acetyl CoA. The solution of the mechanism of this pathway required more than 30 years, in part because the intermediate compounds are bound to enzymes, the enzymes are extremely sensitive to O2 and must be isolated under strictly anerobic conditions, and the role of a corrinoid and CODH was unprecedented. It is now apparent that this pathway occurs (perhaps with some modification) in many bacteria including the methane and sulfur bacteria. In some humans this pathway is catalyzed by the bacteria of the gut and acetate is produced rather than methane; it is calculated that 2.3 x 10(6) metric tons of acetate are formed daily from CO2. A similar synthesis occurs in the hind gut of termites. It is becoming apparent that the acetyl CoA pathway plays a significant role in the carbon cycle.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1900794 TI - Growth factor-induced cell division is paralleled by translocation of Gi alpha to the nucleus. AB - Induction of mitosis by certain growth factors is inhibited by pertussis toxin, indicating that the GTP-binding protein, Gi, is involved in receptor signal transduction to initiate cell division. However, the substrates of receptor activated Gi that are involved in mitosis have not been determined. The present study has examined whether Gi may directly modulate cell division by receptor induced subcellular translocation of the alpha subunit of Gi (Gi alpha). Insulin and EGF, particularly when added together or in combination with phorbol dibutyrate (PdBu), induced a rapid (1-4 h) redistribution of Gi alpha from the plasma membrane to perinuclear sites in the cell. After 2 days of stimulation, Gi alpha had translocated into the nucleus of dividing cells and bound specifically to the separating chromatin of dividing nuclei. Unstimulated cells did not display translocation of Gi alpha. This demonstrates a direct involvement of Gi alpha in cell division, which provides an apparently uninterrupted link from growth factor receptor to nucleus. PMID- 1900795 TI - Mercury released from dental fillings. PMID- 1900796 TI - A complication of PEG change. PMID- 1900797 TI - Direct percutaneous endoscopic jejunostomies. PMID- 1900798 TI - Pneumoperitoneum: a preventable complication of PEG in mechanically ventilated patients. PMID- 1900800 TI - Construction of a family of lactococcal vectors for gene cloning and translational fusion. AB - A family of stable lactococcal vectors have been constructed based on the pFX1 replicon using either the alpha fragment or the complete Escherichia coli lacZ gene as a selective marker. These vectors also incorporate multiple cloning sites and examples are given of their use for gene cloning and translational fusion studies in lactococci. PMID- 1900799 TI - Colocutaneous fistula following migration of PEG tube. PMID- 1900801 TI - [Inhibitory effects of interferon and inhibitors of polyamine biosynthesis on clonal growth of Raji cells derived from Burkitt's lymphoma]. AB - Interferon (IFN)-alpha, -gamma, and two inhibitors of polyamine biosynthesis (alpha-difluoromethyl ornithine; DFMO and methyl glyoxal bis-guanyl hydrazone; MGBG) inhibited the clonal growth of Raji cells. The combination-treatment using two agents, particularly IFN-alpha and DFMO represented synergistic effects. In order to investigate the mechanism of the synergism between IFNs and inhibitors of polyamine biosynthesis, the concentrations of polyamines and the levels of 2' 5' oligo-adenylate synthetase (2-5 AS) activity in the treated Raji cells were determined. Not only the inhibitors of polyamine biosynthesis, but also IFNs decreased the content of spermidine in the cells. Furthermore, the clonogenic growth-inhibition by IFN-alpha was recovered partially by exogenous spermidine. On the other hand, 2-5AS activity in the cells was elevated to 57 times by the treatment with interferon-alpha and further more, the combinations of IFN and the inhibitors of polyamine biosynthesis induced higher activities of 2-5AS as compared with those by each agent. From these results, it was suggested that the synergistic effects of IFNs in combinations with inhibitors of polyamine biosynthesis on the inhibition of clonal growth of Raji cells were closely associated with the decrease of intracellular polyamine level and the increase of 2-5AS activity in the treated cells. PMID- 1900802 TI - [Enhancement of host defence against infection with Listeria monocytogenes in newborn mice by various recombinant cytokines]. AB - Neonatal mice within 24 h of birth were highly susceptible to infection of Listeria monocytogenes. The 50% lethal dose of bacterial cells for neonates and adult mice was 6.3 X 10(1) CFU and 3.2 x 10(6) CFU, respectively. A single intraperitoneal injection of recombinant murine interferon-gamma (rMuIFN-gamma) protected neonates from the simultaneous challenge with a lethal dose of L. monocytogenes. The protection of rMuIFN-gamma was consistently observed in neonates at doses more than 4 X 10(2) IU (0.1 micrograms protein) per mouse. The bacterial growth in the spleens and livers of neonates treated with rMuIFN-gamma was significantly suppressed in comparison with that in the untreated neonates. Furthermore, survived neonates from the infection with L. monocytogenes showed an acquired resistance against the intravenous injection of lethal dose of L. monocytogenes 4 weeks after the primary infection, and this resistance significantly increased in mice that had been treated with rMuIFN-gamma. In addition to rMuIFN-gamma, recombinant human interleukin-1 beta and recombinant human tumor necrosis factor -alpha were also effective on rescue from the lethal infection with Listeria monocytogenes in neonatal mice, but the effect was seen only in the limited doses. On the other hand, recombinant murine IFN-beta and recombinant human IL-2 were not effective at all. These results suggest that rMuIFN-gamma rather than other cytokines might endow neonatal mice with the enhanced antilisterial resistance involving macrophages and T lymphocytes. PMID- 1900803 TI - Factor VIII:C, ABO blood groups, and black admixture in a Brazilian sample. AB - The effects of ABO blood groups and black admixture on the level of factor VIII:C are studied in healthy adults from Salvador, Bahia, Brazil. A racially mixed sample of 125 males was selected as follows: 25 whites, 25 light mulattoes, 25 medium mulattoes, 25 dark mulattoes, and 25 blacks. Levels of both factor VIII:C and K-PTT followed normal distributions. O blood group subjects showed lower factor VIII:C levels (110.20 +/- 30.76%) than non-O blood group members (135.24 +/- 31.42%) (t123 = 4.47; p less than 0.0001) and higher K-PTT levels (37.69 +/- 4.57 s) than non-O blood group subjects (35.25 +/- 3.82 s) (t123 = 3.24; p less than 0.01). By holding ABO blood type constant, there is a significant racial effect (white) on lowering the factor VIII:C level within both blood group O (t43 = 2.23; p less than 0.05) and non-O (t36 = 3.44; p less than 0.002). There is no interaction effect of race and blood group (F = 0.19; p greater than 0.6) on the factor VIII:C levels. PMID- 1900804 TI - Percutaneous endoscopic gastrostomy for enteral feeding. AB - Percutaneous endoscopic gastrostomy was performed for enteral feeding in a patient with orocutaneous fistula. The method of construction of the gastrostomy tube from locally available material is described. PMID- 1900805 TI - Role of enteroclysis in acquired small bowel diverticula. PMID- 1900806 TI - Binding kinetics of Clostridium difficile toxins A and B to intestinal brush border membranes from infant and adult hamsters. AB - This study was undertaken to determine if the relative resistance of neonates and infants to Clostridium difficile-associated intestinal disease can be related to age-dependent differences in intestinal receptors for C. difficile toxins A and B. Brush border membranes (BBMs) from the small intestines of adult and infant hamsters were examined for their ability to bind radiolabeled toxins A and B. [125I]toxin A bound to both infant and adult hamster BBMs at physiological temperature, whereas [125I]toxin B did not bind to the BBMs under any of the conditions examined. The number of [125I]toxin A molecules bound at saturation was approximately 4 x 10(10) per micrograms of membrane protein for adult BBMs and 1 x 10(11) per micrograms of membrane protein for infant BBMs. Scatchard plot analysis suggested the presence of a single class of toxin A binding sites on both infant and adult hamster BBMs. Maximal binding capacity and Kd values were 0.63 pmol/mg of protein and 66.7 nM, respectively, for the infant BBMs, and 0.24 pmol/mg of protein and 27 nM, respectively, for the adult BBMs. Sodium dodecyl sulfate-polyacrylamide gel electrophoretic analyses of extracted BBM proteins revealed differences in the proteins of infant and adult BBMs. However, there were not any detectable differences in the protein bands which bound [125I]toxin A between infant and adult hamsters. The results from these investigations indicate that differences in the binding kinetics of toxins A and/or B to infant and adult hamster BBMs do not account for the observed differences in their susceptibility to C. difficile-associated intestinal disease. PMID- 1900807 TI - Distribution of protein D, an immunoglobulin D-binding protein, in Haemophilus strains. AB - Protein D, a novel surface protein of the bacterial species Haemophilus influenzae with specific affinity for human immunoglobulin (Ig) D was detected in all 127 H. influenzae strains studied. All strains representing different serotypes of encapsulated strains and different biotypes of nonencapsulated strains bound 125I-labeled IgD to a high degree (38 to 74%). Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot (immunoblot) analysis showed that protein D from all H. influenzae strains had the same apparent molecular weight (i.e., 42,000) and reacted with all three different anti-protein D monoclonal antibodies. By Scatchard analysis, the number of protein D residues on a nontypeable H. influenzae strain was estimated to be approximately 2,800 per organism. The equilibrium constant for the reaction between a human IgD myeloma protein and IgD was found to be 5.8 x 10(8) M-1. Also, all strains of H. haemolyticus and H. aegypticus strains tested bound IgD, 21 to 28% and 41 to 48%, respectively. In extracts of those bacteria, a 42,000-molecular-weight protein reactive with IgD and all three anti-protein D monoclonal antibodies was found. In H. parainfluenzae, H. aphrophilus, H. paraphrophilus, and Actinobacillus actinomycetemcomitans, a 42,000-molecular-weight protein that was reactive with one to three of three anti-protein D monoclonal antibodies but not reactive with human IgD was detected with Western blot analysis. Other Haemophilus species (H. ducreyi, H. parasuis, H. parahaemolyticus, H. segnis, and H. haemoglobinophilus) did not react with human monoclonal IgD or anti-protein D antibodies. On the basis of the wide distribution of protein D among H. influenzae strains, we suggest that protein D could be a vaccine candidate. PMID- 1900808 TI - Molecular characterization of the Enterococcus faecalis cytolysin activator. AB - The gene encoding component A (cylA), the activator protein of the Enterococcus faecalis cytolysin, has been localized on pAD1, and the nucleotide sequence was determined. cylA consists of a 1,236-bp open reading frame encoding a 412-amino acid polypeptide. A search of the National Biomedical Research Foundation data base revealed significant homology between the inferred amino acid sequence of component A and subtilisin BPN'. Component A activation of the cytolysin precursor (component L) was observed to be inhibited by the serine protease inhibitor diisopropylfluorophosphate. Mature component A exhibits a molecular weight of approximately 30,000 and an isoelectric point of 4.5. Differences between the size of the primary translation product (45,625 daltons) and the mature enzyme suggest that, as for subtilisin, component A is secreted as a proenzyme. These results provide the basis for a model of component A activation of component L and a role for component A in protecting the cytolysin-producing cell from lysis. PMID- 1900809 TI - Protective immunity induced in Aotus monkeys by recombinant SERA proteins of Plasmodium falciparum. AB - We describe the vaccination of Panamanian monkeys (Aotus sp.) with two recombinant blood stage antigens that each contain a portion of the N-terminal region of the SERA (serine repeat antigen) protein of the malaria parasite Plasmodium falciparum. We immunized with either a 262-amino-acid SERA fragment (SERA I) that contains amino acids 24 to 285 of the 989-amino-acid protein or a 483-amino-acid SERA fragment (SERA N) that contains amino acids 24 to 506 as part of a fusion protein with human gamma interferon. The recombinant proteins were shown to stimulate protective immunity when administered with complete and incomplete Freund adjuvant. Four of six immunized monkeys challenged by intravenous inoculation with blood stage P. falciparum developed parasitemias that were reduced by at least 1,000-fold. Two of six immunized monkeys developed parasitemias which were comparable to the lowest parasitemia in one of four controls and were 50- to 1,000-fold lower than in the other three controls. PMID- 1900811 TI - T-cell proliferative response to antigens secreted by Mycobacterium tuberculosis. AB - An infection model of human tuberculosis was established with C57BL/6J mice. The lymphocyte proliferative responses to antigens from Mycobacterium tuberculosis were investigated during the course of infection and compared with results obtained with a group of mice immunized with large amounts of killed bacteria. The two groups responded similarly to a number of mycobacterial antigens, but marked differences in responses against secreted antigens were found; only infected mice responded vigorously to these. The responding lymphocyte subpopulation was made up of L3T4+ T lymphocytes under restriction of the Ia molecule. PMID- 1900810 TI - Susceptibility to reinfection after a primary chlamydial genital infection is associated with a decrease of antigen-specific T cells in the genital tract. AB - We tested the hypothesis that the intensity of specific antichlamydial T cell mediated immunity in the genital tract of female guinea pigs infected intravaginally with the chlamydial agent of guinea pig inclusion conjunctivitis would determine the resistance or susceptibility to reinfection after a primary chlamydial infection. T cell-enriched lymphocytes were isolated by collagenase treatment of genital tract tissues from either infected or control uninfected female guinea pigs at various times after infection. The nylon wool-enriched T lymphocytes were evaluated for expression of antigen-specific T cell-mediated immunity in vitro by using a blast transformation assay. Both uninfected and infected genital tracts contained T cells, as evidenced by reactivity to concanavalin A, although a greater number of T lymphocytes was detected in the genital tracts of infected animals compared with that in controls. Significant antigen-specific T-cell activity could be detected in the genital tract tissue by 7 days after a primary genital tract infection with the chlamydial agent of guinea pig inclusion conjunctivitis. When antigen-specific activity was assessed at different times after infection, the intensity of the response of genital tract-associated T lymphocytes was directly proportional to the degree of resistance of the animals to genital challenge. Thus, susceptibility of animals to reinfection by chlamydiae appears to be associated with the intensity of the local T cell-mediated immune responses in the genital tract of infected animals. PMID- 1900812 TI - Changes in the ganglioside composition of human neuroblastoma cells under different growth conditions. AB - The ganglioside composition of human neuroblastoma cells (LA-N-1 and LA-N-5) was studied in samples obtained from (1) original cells in tissue cultures, (2) tumors grown in nude mice inoculated with original cells and (3) cells in tissue cultures re-established from the mouse tumors. The amounts of "a" pathway gangliosides (GM2, GM1 and GD1a) and those of the "b" pathway (GD3, GD2, GD1b and GT1b) differed according to the culture conditions. The "b" pathway gangliosides were markedly increased in the tumors grown in nude mice. In contrast, the "a" pathway gangliosides were abundant in cultures of both original and re established cells. We also measured the enzymatic activities of UDP-N acetylgalactosamine: GM3, N-acetylgalactosaminyl transferase (EC 2.4.1.92) and of CMP-N-acetylneuraminic acid: GM3 sialyl transferase (EC 2.4.99.8) in neuroblastoma cells cultured under these conditions. These enzymes are thought to be the key enzymes involved in the synthesis of the "a" and "b" pathway gangliosides. Though there was no significant difference in the activity of N acetylgalactosaminyl transferase between original cells and tumors in nude mice, re-established cells showed a definitely higher activity (3.5 times higher than in the original cells). On the other hand, tumors grown in nude mice had a markedly higher activity of sialyl transferase than that of original cells or re established cells. These findings suggest that the culture conditions and/or the type of cell growth play some role in the synthesis and expression of gangliosides in neuroblastoma cells. PMID- 1900813 TI - Aldolase, glucose-6-phosphate dehydrogenase, superoxide dismutase and aldose reductase activity in the lenses of diabetic rats. PMID- 1900814 TI - Free radical-induced fibrinogen coagulation: modulation of neofibe formation by concentration, pH and temperature. AB - The reaction of fibrinogen with Cu(II) (10-100 microM) and ascorbate (0.1-2.0 mM) leads to the formation of an insoluble clot-like material, "neofibe", which is dependent on experimental conditions. The reaction is observed with human and bovine fibrinogen, in the presence of 0.1-0.3 N NaCl, is optimal at the pH range of 7.4-7.7, and has characteristics typical of a site-specific Fenton reaction. Thus, it is inhibited by EDTA and catalase. Inhibition by mannitol is observed only at relatively high concentrations of this scavenger (greater than 100 mM). Concomitantly, the rate of oxygen utilization increases linearly with the concentration of reagents. The energy of activation of oxygen utilization by ascorbate and Cu(II) in the absence or presence of fibrinogen is Ea = 6.1 and 7.9 Kcal/mol, respectively. These values suggest that the rate-limiting step is dictated by a reaction of oxygen with "free" or protein-bound copper cations. The temperature dependency of the extent of transformation of human and bovine fibrinogen into neofibe is unusual in that it is biphasic-increasing from 5 to 25 degrees C, and decreasing thereafter, to 43 degrees C. This is not due to the temperature stability of fibrinogen. The essential requirement for copper, ascorbate and oxygen or hydrogen peroxide, as well as the low efficiency of mannitol as a scavenger, are in accord with the most likely interpretation of these data that fibrinogen undergoes a site-specific Fenton reaction. This modifies the protein and results in the formation of insoluble, polymeric, neofibe aggregates. PMID- 1900815 TI - Current status of whole-body counting as a means to detect and quantify previous exposures to radioactive materials. Whole-body Counting Working Group. AB - This report discusses the principles, techniques, and application of whole-body counting with respect to previous radiation exposure. Whole-body counting facilities are located nationwide and have a wide range of capabilities. A listing of these facilities is provided in Appendix A. However, only a few facilities are truly state-of-the-art and have the sophisticated capabilities required to attempt detection of low-level activity in vivo. Measurements made many years after exposure can be extremely difficult to interpret. The precision and accuracy of resulting dose estimates are functions of such factors as the assumptions made concerning intake, time since intake, radionuclide metabolism, and level of intake. The indiscriminate application of metabolic models to current body contents or minimum detectable amounts of radionuclides with relatively short effective half-lives (such as 137Cs) can lead to absurd results when used as a basis for calculating intakes 25 and 40 y ago. Skull counting for 90Sr-90Y and 239,240Pu can set upper limits on possible uptakes and radiation doses, but in the case of 239,240Pu, the limits are rather high. In both cases, the accuracy of the limits depends on the metabolic models used in the calculations. These models (ICRP 1979) were developed to set safety standards for the intakes of radionuclides by workers and are not intended to be used to back calculate uptakes and radiation doses from measurements made long after the uptake. There are, therefore, large uncertainties in any conclusions derived from these calculations. The experience gained over the years with whole- and partial body counting has consistently shown that they are of little use in determining body contents of radionuclides resulting from exposure to weapons debris decades earlier. The development of new detectors such as an array of lithium-drifted silicon devices offers some hope of lowering the minimum detectable amount (MDA) for Pu and Am, but such detectors are still several years from routine application and do not represent current state-of-the-art. Furthermore, it is doubtful that such improvements will be sufficient to meet the need of assessing radiation exposures that occurred decades earlier. PMID- 1900816 TI - Panfibrinonecrotic colitis in a dog treated by subtotal colectomy. AB - A dog with signs of small intestinal disease developed signs of severe large intestinal disease after being treated with multiple agents. Endoscopy and biopsy revealed total destruction of the colonic mucosa, which necessitated total parenteral nutrition plus subtotal colectomy. It was hypothesized that the multiple prior treatments led to an overgrowth of toxigenic or cytotoxic bacteria, which caused this colonic mucosal destruction. PMID- 1900817 TI - Induction of aberrant crypt foci in the large intestine of F344 rats by oral administration of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine. AB - Carcinogenicity of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) to rat colon was investigated using the appearance of colonic aberrant crypt (AC), a preneoplastic lesion, as a marker. The number of AC foci per colon at experimental week 4 was 1.3 +/- 0.8; almost half the level of AC foci induced by 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (Glu-P-1), which is a known colon carcinogen. No ACs were observed in rats of the control group. A repeat experiment showed that induction of AC foci by PhIP administration was reproducible and a significant increase in the number of AC foci, 3.0 +/- 0.0, was observed after 12 weeks of PhIP administration. The majority of ACs induced by PhIP were localized in the distal part of the colon. The distribution was similar to those induced by Glu-P-1 and 1,2-dimethylhydrazine. Those data suggested that PhIP is possibly carcinogenic to rat colon. PMID- 1900818 TI - A smoking survey of college students in India: implications for designing an antismoking policy. AB - A survey of 599 college students was conducted in Andhra Pradesh, India, to formulate an anti-smoking policy for youth. There were 64.6% boys and 35.4% girls between 15 and 22 years, and 8.2% of students (n = 49, 48M + 1F) were smokers. It is a taboo for girls to smoke. There is no current anti-smoking policy and one is proposed based on the smoking survey results. The policy includes parental pressure to curb smoking, and a ban on (1) advertising of tobacco products, (2) smoking in public places and (3) teachers smoking in school. An increase in the price of cigarettes was approved by a majority of the students. The survey revealed a gap in the knowledge of students about the ill effects of smoking, which can be rectified by health education programs. PMID- 1900819 TI - Carcinogenesis studies of dichlorvos in Fischer rats and B6C3F1 mice. AB - Dichlorvos (dichlorovinyl dimethyl phosphoric acid ester) is a cholinesterase inhibitor used widely as a contact and stomach insecticide for control of internal and external parasites. Carcinogenesis studies were conducted by administering dichlorvos in corn oil by gavage 5 times a week for 103 weeks to groups of 50 male and 50 female Fischer rats at 0, 4, or 8 mg/kg body weight, to groups of 50 male B6C3F1 mice at 0, 10, or 20 mg/kg, and to groups of 50 female B6C3F1 mice at 0, 20, or 40 mg/kg. During the course of the studies, body weights and survival rates of the male and female rats and mice were not different from those of their respective controls; females of both species appeared to gain more weight than controls. Neoplasms induced by dichlorvos included adenomas of the exocrine pancreas (male rats), mononuclear cell leukemia (male rats), and squamous cell papilloma of the forestomach (male and female mice; two other female mice had squamous cell carcinomas). Lesions observed in female rats that may have been due to dichlorvos administration included adenomas of the exocrine pancreas and fibroadenomas of the mammary gland. The results demonstrated that dichlorvos is carcinogenic for Fischer rats and B6C3F1 mice. PMID- 1900821 TI - Induction of DNA replication and cell growth in rat liver by obstructive jaundice. AB - Obstructive jaundice, produced by ligating the common bile duct, induced a transient DNA replication followed by cell proliferation in rat liver. At 48 h after the operation, DNA polymerase alpha activity started to increase and reached its maximum level (more than twice the control) at day 4. At day 7, the enzyme level had decreased to the control level. Pulse-labeling experiment using radioactive thymidine showed that the rate of DNA synthesis increased approximately 2.5-fold in the same pattern as that of DNA polymerase alpha. The mitotic index in hepatocytes also increased 10-fold at day 4 and then decreased. The proliferation of liver cells induced by obstructive jaundice mimics the regeneration of partially hepatectomized liver, although the response was slightly delayed and the proliferation was transient. PMID- 1900820 TI - Relation of 8-hydroxydeoxyguanosine formation in rat kidney to lipid peroxidation, glutathione level and relative organ weight after a single administration of potassium bromate. AB - Changes in kidney levels of 8-hydroxydeoxyguanosine (8-OH-dG), lipid peroxidation (LPO), glutathione (GSH) and relative organ weight were examined 6, 24, 48, 72 and 96 h after a single i.p. administration of potassium bromate (KBrO3) at a dose of 70 mg/kg to male F344 rats. The 8-OH-dG level was significantly increased 24 h after the treatment at this dose and thereafter gradually decreased. On the other hand, significant elevation in LPO level was observed from 6 h after the treatment with a continuous increase up to a plateau at 48 h and no subsequent drop. GSH level was significantly raised from 6 to 72 h, and relative kidney weight varied in almost the same manner as the 8-OH-dG level. Investigation of the dose-response relation revealed the 8-OH-dG and LPO levels to be significantly increased from a dose of 40 mg/kg KBrO3 in a dose-dependent manner. The results suggest that enhanced formation of 8-OH-dG in kidney DNA due to KBrO3 is closely related to the increase in LPO levels. PMID- 1900823 TI - Objective quantification of grade of atypia in epithelial tumors of the stomach by image processing. AB - An image processing technique to extract tubular and nuclear areas from histological specimens stained with hematoxylin was established. Two indices representing tubular density and nucleus-to-cytoplasm ratio of glands were examined in intestinal-type tumor of the stomach. In specimens clearly stained with hematoxylin, significant differences of brightness among nuclei, cytoplasm and stroma can be obtained. Image processing by computer enabled us to identify nuclei, cytoplasm and stroma by utilizing the differences of brightness among them. Both indices tended to increase with severity of histological atypia and their values in the tubular adenoma group were significantly different from those in the tubular adenocarcinoma group (P less than 0.05). Therefore, these two indices could be regarded as valid and objective measures of the grade of histological atypia. Eighty-four percent of tubular adenoma and tubular adenocarcinoma cases were classified correctly with the discriminant formula and critical value calculated from the two indices on the basis of measurement of the images magnified by 40 times. There is, however, still a non-negligible overlap of discriminant scores between the tubular adenoma group and tubular adenocarcinoma group. More indices representing histological atypia will be required to allow objective differential diagnosis between malignant and benign lesions. PMID- 1900822 TI - Provirus integration at the 3' region of N-myc in cell lines established from thymic lymphomas spontaneously formed in AKR mice and a [(BALB/c x B6)F1----AKR] bone marrow chimera. AB - Among 18 thymic leukemia cell lines which have been established from spontaneous thymic lymphomas in AKR mice as well as in bone marrow chimeras which were constructed by transplanting allogeneic bone marrow cells into irradiated AKR mice, three proviral integration sites were identified; near c-myc, N-myc and pim 1 loci. No integration site specific for chimeric leukemia cell lines was found. In three thymic leukemia cell lines which contained rearranged N-myc genes, insertions of long terminal repeats (LTRs) of murine leukemia viruses were detected at 18 or 20 bp downstream of the translational termination codon. These results demonstrate that the 3' region of the N-myc gene is one of the integration targets for murine leukemia viruses in spontaneous thymic lymphomas. In these three cell lines, N-myc mRNA was stably transcribed and transcription of c-myc mRNA was down-regulated. The integrated murine leukemia viruses in AKR thymic leukemia were most likely AKV, though the DNA sequence of the LTR inserted in the genome of a leukemic cell line from [(BALB/c x B6)F1----AKR], CAK20, was different from LTRs of murine leukemia viruses so far reported. PMID- 1900824 TI - Release of esterase from murine lymphokine-activated killer cells in antibody dependent cellular cytotoxic reaction. AB - Release of granule enzyme(s) (BLT esterase) in the antibody dependent lymphokine activated killer (LAK) cell-mediated cytotoxic reaction (LAK ADCC) was studied using LAK cells induced from murine splenocytes and thymocytes, various human tumor cells and relevant monoclonal antibodies (mAbs) to the tumor cells. BLT esterase was not significantly released from LAK cells in direct LAK cell mediated cytotoxic reactions (LAK CMC). However, cultures of LAK cells and IgG coated target tumor cells resulted in release of the enzyme concomitantly with target cell lysis, although esterase release proceeded faster than target cell lysis. Anti-LFA-1 mAb showed an inhibitory effect on LAK CMC but not on either LAK ADCC or BLT esterase release in the ADCC. These results indicate that exocytosis of granule enzyme from LAK cells is triggered by stimulation of Fc receptor on LAK cells and that LAK CMC and LAK ADCC differ in their lytic mechanism in terms of the release of BLT esterase. PMID- 1900825 TI - Human monoclonal antibody detects a cell surface antigen expressed on hematopoietic malignant cells of lymphoid lineage. AB - An antigen with a molecular weight of 150 kilodaltons expressed on certain leukemia and lymphoma cells was recognized by a human monoclonal antibody (3H12), which had been established by the fusion of lymphocytes from a small cell lung cancer patient with a mouse myeloma cell line (P3U1). Peripheral blood mononuclear cells from 3 out of 4 cases with lymphoid crisis of chronic myelogenous leukemia (CML) were positively stained by 3H12, while cells from 5 cases with myeloid crisis of CML did not react to this antibody. The antibody did not show any reactivity to cells from the chronic phase of CML, other types of leukemias or normal hematopoietic cells. We further examined 29 cell lines of hematopoietic origin and found that 2 undifferentiated cells (BV-173 and K-562) reacted to the 3H12 antibody. In addition, we found that 3 out of 6 Burkitt lymphoma cells (DAUDI, RAJI and HR1K) reacted to 3H12. Taken together, these results suggest that the antigen recognized by 3H12 is a differentiation associated antigen expressed on immature lymphoid cells, and could potentially be a reliable cell lineage marker. PMID- 1900826 TI - Preparation of recombinant protein A-lymphotoxin chimeric protein and its antitumor effects in mice. AB - We have investigated the in vivo function of a chimeric protein constructed by recombinant DNA techniques. The behavior and antitumor activity of a protein A lymphotoxin chimera (ALT) was examined on a murine tumor in mice in comparison with amino-terminal 19 amino acid-deleted lymphotoxin (dLT). Seven-week-old male BALB/c mice were implanted intradermally with Meth-A fibrosarcoma on day 0. ALT and dLT caused tumor regression, hemorrhagic necrosis and complete regression in a dose-related way when each agent was given intratumorally 5 times (days 5-9). The ratio of the median effective doses for complete tumor regression was 1.6 between ALT and dLT on a molar basis. ALT caused tumor regression and body weight loss when given intravenously on the same schedule. Biodistribution studies with 125I-labeled ATL and dLT demonstrated that, after intratumoral administration, ALT was retained longer in the administered site and was cleared more slowly from the mouse body than dLT. These findings suggest that a protein A-lymphotoxin chimeric protein expresses both antitumor activity similar to that of lymphotoxin and characteristic in vivo behavior of the fused protein A portion. PMID- 1900827 TI - FSH injections and intrauterine insemination in protocols for superovulation of ewes. AB - In Exp. 1, five injections of crude FSH (20 mg total), starting 36 h before removal of progestin pessaries or injection of prostaglandin F2 alpha (PGF2 alpha), were found to be as effective for superovulation of ewes as seven injections starting 72 h before removal of pessaries. Seven injections caused superovulation (more than three ovulations) in 13 of 15 ewes with an average (all ewes) of 12 +/- 2.3 ovulations. Five injections caused superovulation in 17 of 19 ewes with an average of 11.5 +/- 1.6 ovulations after pessary-regulated estrus in 12 of 16 ewes with an average of 12.4 +/- 2.2 ovulations after PGF2 alpha injection. In Exp. 2, intrauterine artificial insemination (IUAI) of naturally mated ewes provided ovum fertilization rates of 75.3% with an embryo recovery rate of 39.4%, whereas mating alone (MATED) provided fertilization rates of 64.2% with an embryo recovery rate of 72.1%. However, subsequent replications of the MATED protocol (MATED2) resulted in a low fertilization rate (34.2%). In Exp. 3, surgical IUAI at 22 h after removal of pessaries resulted in a low rate of superovulation (5 of 12 ewes), presumably as the result of pentobarbital anesthesia. Conducting IUAI at 46 h after removal of pessaries resulted in a high rate of superovulation (14 of 16 ewes) but a low embryo recovery rate (30.7%). In two subsequent trials, IUAI at 40 h after removal of pessaries resulted in most ewes superovulating (33 of 35 in April/May and 16 of 17 in September) with acceptable embryo recovery (65.2% and 71.3%) and high fertilization rates (82.8% and 96.4%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1900828 TI - Pituitary and testicular responses of beef bulls to active immunization against inhibin alpha. AB - Prepubertal crossbred beef bulls served as controls or were actively immunized against the N-terminal, 30-amino acid synthetic fragment of porcine inhibin alpha, pI alpha (1-30). Antibody titers were detected in sera (greater than 40% B/BO in sera diluted 1,000-fold) but not in rete testis fluid of 390-d-old bulls. Serum FSH and inhibin remained static during a 5-h intensive bleed; inhibin was not acutely affected by a 15-fold LH rise and a threefold FSH rise induced by exogenous GnRH. Serum FSH, but not LH or testosterone, was consistently elevated (P less than .05) in immunized bulls compared with control bulls. Neither pituitary weight, pituitary gonadotropin content nor pituitary FSH/LH ratios were affected (P greater than .10) by pI alpha(1-30) active immunization. Testicular sperm density was greater (60 x 10(6) vs 45 x 10(6) sperm/g testis; P less than .10) in immunized bulls, but testes weight, epididymides weight and total daily sperm production remained unchanged. These results suggest that inhibin is important for regulation of FSH secretion and testicular function. Immunization with suitable inhibin vaccines may improve bull fertility. PMID- 1900829 TI - Prepubertal changes in plasma FSH and inhibin in Holstein bull calves: responses to castration and(or) estradiol. AB - The objectives of two studies were to determine 1) whether plasma concentrations of inhibin (INH) changed with age in prepubertal bulls and whether these changes were related to changes in FSH, testosterone or testis length; and 2) whether castration and(or) estradiol implants affected plasma concentrations of INH and FSH. In Exp. 1, plasma INH remained constant from 4 until 8 wk of age then increased from 120 pM to 202 pM between 8 and 12 wk. Thereafter, INH decreased to 90 pM by 36 wk. Between 4 and 10 wk, plasma FSH increased from .32 to .43 ng/ml, apparently increasing before the initial rise in plasma INH. Between 10 and 12 wk, FSH declined from .43 to .33 ng/ml. After 12 wk, FSH increased as INH decreased. Initial increases in testis length and concentrations of plasma testosterone occurred at 14 wk coincident with the second rise in FSH. In Exp. 2, bull calves were either left intact, castrated, castrated and implanted with estradiol, or left intact and implanted with estradiol at 7.5 wk of age. Castration decreased concentrations of INH and increased concentrations of FSH. Castrated calves implanted with estradiol had decreased concentrations of both INH and FSH. Intact bulls implanted with estradiol had decreased concentrations of FSH relative to intact unimplanted bulls; however, concentrations of INH did not display the age-related changes observed in intact, unimplanted bulls. In summary, age-related changes in plasma INH and FSH occur in bulls. Furthermore, plasma concentrations of INH and FSH increased before changes in gonadal size were detected. The bovine testis may be a major source of circulating INH because castration decreased concentrations of plasma INH. PMID- 1900830 TI - Variation among Angus cows in response to endophyte-infected fescue seed in the diet, as related to their past calf production. AB - Production of 18, 12-yr-old Angus cows was summarized as the averaged weaning weight deviations of each cow's calves from their like-aged, like-sexed and similarly managed contemporaries. These cows had spent a large part of their productive lives on pastures dominated by endophyte-infected tall fescue, so differences among them in calf production might have been induced partly by differences in susceptibility to fescue toxicosis. Cows were divided randomly into two groups for a 31-d summer feeding trial. In a crossover design, cows were fed 0 or .9 kg per cow per day of endophyte-infected fescue seed. Various traits were monitored to quantify differences among cows in response to the endophyte infected fescue seed. Baseline serum prolactin concentration was depressed by fescue seed feeding, but differences among cows in the amount of depression were not related to past calf production. Prolactin release in response to thyrotropin releasing hormone tended to be depressed by fescue, but the response also was sensitive to factors such as ambient temperature. Serum cholesterol and body weight change did not respond significantly to the fescue challenge. The experiment was not successful in unambiguously differentiating among cows in susceptibility to fescue toxicosis or in relating differential susceptibility to past calf production. PMID- 1900831 TI - Lithium treatment of chronic hair pulling. AB - Ten patients with chronic hair pulling received trials of lithium carbonate of 2 to 14 months' duration. Eight patients demonstrated decreased hair pulling and mild to marked hair regrowth. Three responders experienced increased hair pulling subsequent to discontinuation of lithium treatment. Lithium's effect on hair pulling may be related to its observed benefits in treating aggressivity, impulsivity, and mood instability. PMID- 1900832 TI - Rapid treatment of depression with selegiline-phenylalanine combination. PMID- 1900833 TI - Cytosol promotes the guanine nucleotide-induced release of the alpha subunit of Gi2 from the membrane of mouse mastocytoma P-815 cells. AB - Translocation of the alpha subunit of Gi2 from the membrane to the cytosol was studied in mouse mastocytoma P-815 cells. To monitor Gi2 alpha the membrane (300,000 x g pellet) was [32P]ADP-ribosylated with pertussis toxin. Incubation of the [32P]ADP-ribosylated membrane with guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) caused a small release (10%) of [32P]ADP-ribosylated Gi2 alpha from the membrane. Whereas cytosol (300,000 x g supernatant) alone had no ability to release the [32P]ADP-ribosylated Gi2 alpha from the membrane, it markedly augmented the release induced by GTP gamma S, about 50% of the total [32P]ADP ribosylated Gi2 alpha being released by 30 min. The GTP gamma S-induced release and its enhancement by the cytosol were specific for GTP and GTP gamma S. When the cytosol was boiled this promoting activity was lost. The [32P]ADP-ribosylated Gi2 alpha released by the cytosol plus GTP gamma S from the membrane was eluted as a single peak corresponding to a molecular weight of about 100,000 from an Ultrogel AcA 44 column. In contrast, the [32P]ADP-ribosylated Gi2 alpha released by GTP gamma S alone was eluted at the position of Mr = 40,000, but it was eluted at the position of Mr = about 100,000 when it was incubated with the cytosol. Furthermore, Gi2 alpha purified from bovine lung also behaved in a similar way on gel filtration. The addition of thrombin, a stimulant of histamine secretion from mast cells, to mastocytoma cells drastically induced the translocation of Gi2 alpha from the membrane to the cytosol in a pertussis toxin-sensitive manner. These results taken together demonstrate that the cytosol contains some factor(s) that promotes the release of GTP-activated Gi2 alpha from the membrane and that the released Gi2 alpha exists in the cytosol as a soluble complex with unidentified component(s) in mastocytoma cells. PMID- 1900834 TI - Roles of the D-ribose and 5,6-dimethylbenzimidazole moieties of the nucleotide loop of adenosylcobalamin in manifestation of coenzymic function in the diol dehydrase reaction. AB - Coenzyme analogs in which the D-ribose moiety of the nucleotide loop was replaced by an oligomethylene group and a trimethylene analog containing imidazole instead of 5,6-dimethylbenzimidazole were synthesized. Coordination of the 5,6 dimethylbenzimidazole to the cobalt atom in these analogs was much weaker than that in cobalamins. The replacement of this base with imidazole did not significantly alter the strength of the coordination to the cobalt atom. 5,6 Dimethylbenzimidazolyl trimethylene and tetramethylene and imidazolyl trimethylene analogs were partially active as coenzymes in the diol dehydrase reaction in this order as judged by kcat, but the others were not active as coenzymes and were weak competitive inhibitors. This indicates that neither the alpha-D-ribofuranose ring nor the functional groups of the ribose moiety are essential for coenzymic function. There was an optimum loop size of the analogs for catalysis and for tight binding to the apoenzyme, which corresponds to the loop size of cobalamins. Therefore, the D-ribose moiety seems important as a spacer to keep the base in the proper position. The reaction with the imidazolyl trimethylene analog as coenzyme was accompanied with concomitant rapid inactivation during catalysis. The inactivation occurred only in the presence of substrate. Upon inactivation with this analog, 5'-deoxyadenosine and a B12r-like species were formed from the adenosyl group and the rest of the analog molecule, respectively, without modification of the apoenzyme. Therefore, it can be concluded that this is a kind of suicide inactivation which occurred from one of the intermediates in the normal catalytic process. The dimethylbenzo moiety of the regular coenzyme thus seems to play an important role in preventing the intermediate complexes from inactivation during catalysis. PMID- 1900835 TI - Soluble 14-kDa beta-galactoside-specific bovine lectin. Evidence from mutagenesis and proteolysis that almost the complete polypeptide chain is necessary for integrity of the carbohydrate recognition domain. AB - The soluble beta-galactoside-specific bovine lectin of subunit 14 kDa has been expressed in vitro by transcription and then translation in a rabbit reticulocyte lysate. The protein thus expressed shows the predicted binding to lactose coupled to Sepharose. Several mutants of the 134 amino acid protein have been expressed and insight gained into (a) the polypeptide length required to form the carbohydrate recognition domain and (b) the functional importance of some of the highly conserved amino acids. The following amino acids have been deleted: 1-9, 1 23, 88-122, 88-134, 107-134, or 124-134. In addition, a frame-shift mutant has been made in which the 23 amino acids at the C-terminal end were completely changed. Among these seven mutants only mutant 1-9 shows carbohydrate binding but with congruent to 30% of the activity of the wild-type protein (as assessed by the percentage of the protein bound to lactose-Sepharose). On the other hand, carbohydrate binding is relatively well preserved (75-90%) in mutant proteins where the C-terminal octapeptide sequence of the bovine lectin has been changed to sequences that resemble those in the chick 14-kDa lectin. When the single tryptophan at position 68 is changed by point mutagenesis to phenylalanine or to a leucine residue, a weak binding activity (congruent to 20%) is retained only with the former. When either of the cysteines 2 or 60 is changed to serine, binding activity is reduced to congruent to 60%, and when both are changed, to congruent to 20% of that for the wild-type protein. The susceptibility of the lectin to oxidative inactivation is unaffected when these 2 cysteines and cysteine 130 are changed to serine individually or in tandem (cysteines 2 and 60). In a second approach we show that the natural protein isolated from bovine heart is protected from proteolysis by trypsin and V8-protease in the presence of saccharide ligand. Although further work is required to identify residues which come into contact with the carbohydrate ligand, these results indicate that almost the complete polypeptide chain is necessary for the integrity of the carbohydrate recognition domain. PMID- 1900836 TI - Synapsin I is a highly surface-active molecule. AB - Synapsin I is a neuron-specific phosphoprotein localized on the surface of small synaptic vesicles to which it binds with high affinity (Kd = 10 nM). Synapsin I exhibits a tendency to self-associate, suggesting that it might have amphiphilic properties. We have now found that synapsin I forms a stable monolayer at an air water interface which can be compressed under a lateral force of up to 60 dynes/cm, indicating the presence of amphiphilic characteristics in its structure. This interpretation was also supported by circular dichroism spectra of synapsin I, which showed induction of secondary structure in the presence of trifluoroethanol. The various phosphorylated forms of synapsin I did not show any noticeable differences in the force-area isotherms. The monolayer properties of synapsin I fragments derived by cysteine-specific cleavage indicated the presence of amphiphilic characteristics throughout the entire sequence, although the C terminal region showed less of such surfactant properties. Compositional studies of these fragments revealed that there is little interaction between the N terminal and middle fragment regions, but that there may be some interaction between the C-terminal and middle fragment regions which affects the surface area occupied by these fragments. Based on this information, we propose a molecular topology for synapsin I consisting of amphiphilic regions and a hydrophilic region. PMID- 1900837 TI - Characterization and purification of the 94-kDa glucose-regulated protein. AB - Increased synthesis of so-called glucose-regulated proteins (grp) of 78 and 94 kDa occurs in mammalian cells exposed to a variety of agents, including 2 mercaptoethanol, tunicamycin, agents which perturb calcium homeostasis, and amino acid analogs. Herein we describe a number of properties of 94-kDa grp (grp 94) and present a method for its purification to homogeneity. The protein, within the endoplasmic reticulum (ER), is modified by the addition of high mannose containing oligosaccharides. The predicted amino acid sequence of grp 94, as determined by others, has revealed the protein to contain a putative transmembrane domain near its amino terminus, but in addition, a potential endoplasmic reticulum retention sequence (KDEL) at its COOH terminus. Consequently, the question of whether grp 94 exists as a transmembrane or luminal protein of the ER remains controversial. Results using isolated microsomes subjected to either limited proteolysis or lactoperoxidase-mediated iodination were consistent with the idea that the grp is a transmembrane protein. On the other hand, using the method of sodium carbonate extraction, grp 94 exhibited properties of both a luminal and integral membrane protein. These results raise the question of whether there exist two different forms of grp 94 within the ER. PMID- 1900838 TI - Characterization of the catalytic subunit of casein kinase II expressed in Escherichia coli and regulation of activity. AB - The catalytic (alpha) subunit of casein kinase II from Drosophila, cloned and expressed in Escherichia coli (Saxena, A., Padmanabha, R., and Glover, C. V. C., (1987) Mol. Cell. Biol. 7, 3409-3417), has been purified and characterized, and the properties have been compared to those of the holoenzyme. The catalytic subunit exhibits protein kinase activity with casein as substrate and is autophosphorylated. The specific activity of the purified subunit is 6% of the activity of the holoenzyme from reticulocytes or from Drosophila. The alpha subunit is a monomer, eluting at Mr = 40,000 upon gel filtration in high salt, but as part of an aggregate in low salt. The alpha subunit has been purified to apparent homogeneity by sequential chromatography on DEAE-cellulose, Mono S, and Mono Q. A single band, Mr = 37,000, is detected by silver staining following polyacrylamide gel electrophoresis. The isolated alpha subunit displays apparent Km values for beta casein, ATP, and GTP similar to those of the holoenzyme. The activity of the alpha subunit is inhibited by heparin with an I50 of 0.1-0.3 micrograms/ml, a value similar to that observed for the holoenzyme; autophosphorylation is also inhibited by heparin. Polylysine has no stimulatory effect on the activity of the catalytic subunit, as measured with casein and by autophosphorylation, but stimulates both activities with the holoenzyme. When physiological substrates for casein kinase II are examined, glycogen synthase and eukaryotic initiation factor 3 (eIF-3) (p120) are phosphorylated by the alpha subunit at a rate equivalent to that of the holoenzyme, while phosphorylation of eIF-3 (p67) is reduced 9-fold and eIF-2 beta is not modified. From these data, it can be concluded that the alpha subunit of casein kinase II is sufficient for catalysis, is autophosphorylated, and can be directly inhibited by heparin, whereas the beta subunit mediates the effects of basic stimulatory compounds and is involved in recognition and/or binding to specific physiological substrates. PMID- 1900839 TI - Regulation of c-jun expression and AP-1 enhancer activity by granulocyte macrophage colony-stimulating factor. AB - Granulocyte-macrophage colony stimulating factor (GM-CSF) stimulates the growth and differentiation of human hematopoietic progenitor cells by activating transcription of specific genes. The mechanism by which binding of GM-CSF to its receptor stimulates gene expression remains unknown. To examine this process in more detail, we have transfected human monocytic leukemia cells U937 with a plasmid containing an AP-1 enhancer element and a chloramphenicol acetyltransferase recorder gene and treated them with GM-CSF. We find that GM-CSF stimulates a 2-3-fold increase in chloramphenicol acetyltransferase activity over a concentration range 1-1,000 units/ml. Northern and Western blot analysis demonstrates that the mechanism by which GM-CSF stimulates AP-1 enhancer activity involves increases in c-jun and c-fos mRNA levels, and increases in Jun protein. In a similar fashion the treatment of normal human monocytes with GM-CSF also induced increases in total cellular c-jun. Because protein kinase C plays a crucial role in activating c-jun transcription we examined the role of this enzyme in mediating the effects of GM-CSF. Treatment of U937 cells with inhibitors of protein kinase C including staurosporine 10 nM and H-7 50 microM, or down-regulation of protein kinase C by phorbol ester pretreatment blocks the induction of c-jun by GM-CSF. However, HA which does not block protein kinase C had no effect on GM-CSF stimulation of c-jun RNA levels. In addition, GM-CSF treatment causes the rapid translocation of protein kinase C to the particulate fraction which was maximal by 5 min and returned to base line by 80 min. These data suggest that the binding of GM-CSF to its receptor stimulates increases in c jun mRNA and protein and activates AP-1 enhancer activity. These effects may be at least in part mediated by activation of protein kinase C. PMID- 1900840 TI - Promoter elements and factors involved in hepatic transcription of the human ApoA I gene positive and negative regulators bind to overlapping sites. AB - DNase I footprinting analysis of the proximal apoA-I promoter sequences with rat liver nuclear extracts identified four protected regions: A, -22 to +17; B, -128 to -77; C, -175 to -148; and D, -220 to -190. Region D (-220 to -190) binds at least two distinct activities, designated AID1 and AID2, respectively, which can be separated by ion exchange chromatography. Region C (-175 to -148) forms five DNA protein complexes. Three of the complexes (2, 4, and 5) originate from the binding of more than one heat-stable nuclear factor, and two (1 and 3), from the binding of two heat-labile factors. The heat-stable factors bind in the -175 to 148 region and can be distinguished from C/EBP, which recognizes the same region, with DNA binding gel electrophoretic assays. Both factors 1 and 3 bind in the 168 to -148 apoA-I region. Despite the lack of a CCAAT motif in this region, the binding of factor 1 is competed out by oligonucleotides containing the binding sites of NFY and NFY*. Mutagenesis of the promoter region showed that mutations in the -171 to -166 and -158 to -153 regions diminished the binding of the heat stable factors and reduced hepatic transcription to 14 and 8% of control, respectively. In contrast, a mutation in the -164 to -159 region abolished the binding of factor 1 and was associated with a 4.6-fold increase in hepatic transcription. These findings suggest that the heat-stable factors act as positive regulators, whereas factor 1 acts as a negative regulator in apoA-I gene transcription. PMID- 1900841 TI - Heterotopic bone formation after hip replacement. The influence of the type of osteoarthritis. AB - The relationship between heterotopic bone formation and the morphological type of osteoarthritis was examined after 43 hip replacements. Of the 43 hips studied, nine were atrophic, 19 were normotrophic, and 15 were hypertrophic. The incidence of heterotopic bone formation in the atrophic type was 11%, in the normotrophic type 32%, and in the hypertrophic type 87%. The difference between each type was statistically significant (p less than 0.001). PMID- 1900842 TI - von Recklinghausen's neurofibromatosis with neurofibrosarcoma. PMID- 1900843 TI - Association of cellular thiol redox status with mitogen-induced calcium mobilization and cell cycle progression in human fibroblasts. AB - Human gingival fibroblast cultures were used to investigate the role of cellular thiol redox status in the mitogenic response. Increases in intracellular Ca2+ and cell cycle progression beyond G1 were followed as parameters of cellular mitogen induced responses. Ethionine provided a G1 stage synchronization and altered the cellular redox poise as measured by the ratio NAD(P)H/NAD(P)+. Cultures harvested immediately after the 6 day ethionine low-serum synchronization showed a significant oxidation of their redox poise. Synchronized cultures, which were also glutathione (GSH) depleted, still showed an oxidized redox poise and significantly reduced GSH levels following a 24 hr incubation in drug-free, rich medium. Cellular reduced nicotinamide nucleotide levels correlated strongly (r = 0.995) with capacity to mobilize intracellular Ca2+ in response to basic fibroblast growth factor (bFGF). The sustained mitogenic response, as determined by cell cycle progression beyond G1, was also found to be interrelated with the cellular thiol redox status. Following a 24 hr recovery incubation in serum-rich medium, formerly synchronized cultures showed a rebound of their redox poise to a more reduced state and significant cell cycle progression beyond G1. In contrast, synchronized, GSH-depleted cultures did not progress and showed population distributions similar to those of cultures harvested immediately postsynchronization. Upon recovery of cellular GSH and reduced nicotinamide nucleotide levels, formerly GSH-depleted, growth-arrested cultures resumed cell cycle progression. The results suggest that the cellular response to specific mitogens is interrelated with the cellular thiol redox status. Cells that possess a thiol redox status below a threshold response point may have compromised Ca2+ sequestration and/or mobilization and therefore may be incapable of initiating the mitogen induced response cascade that culminates in cell cycle progression. PMID- 1900844 TI - Phenotype suppression: a postulated molecular mechanism for mediating the relationship of proliferation and differentiation by Fos/Jun interactions at AP-1 sites in steroid responsive promoter elements of tissue-specific genes. AB - There is a generalized reciprocal relationship between cell growth and expression of genes that occurs following completion of proliferation, which supports the progressive development of cell and tissue phenotypes. Molecular mechanisms which couple the shutdown of proliferation with initiation of tissue-specific gene transcription have been addressed experimentally in cultures of primary diploid osteoblasts that undergo a growth and differentiation developmental sequence. Evidence is presented for a model which postulates that genes transcribed post proliferatively are suppressed during cell growth by binding of the Fos/Jun protein complex to AP-1 promoter sites associated with vitamin D responsive elements of several genes encoding osteoblast phenotype markers (Type I collagen, alkaline phosphatase, osteocalcin). PMID- 1900845 TI - Current status of HIV therapy: II. Opportunistic diseases. AB - Infections and malignancies account for most deaths in patients with AIDS--and will continue to do so as long as HIV-induced immunosuppression is progressive and irreversible. Options available for prevention and improved management of such diseases are changing as new agents emerge, new combinations of agents are developed, and new indications for available agents are identified. PMID- 1900846 TI - Acute and chronic schistosomiasis. PMID- 1900847 TI - The MAD PHYSICIAN and hypercalcemia. PMID- 1900848 TI - Twisted arms and ethical choices. PMID- 1900849 TI - Withholding and withdrawing life support. AB - What does the physician do when health cannot be restored or suffering relieved? When the fundamental principles of biomedical ethics are used as guidelines for life support decisions, patients, their families, and the medical staff all benefit. These principles--beneficence, nonmaleficence, autonomy, and justice- are discussed in the context of legal precedents and clinical application. PMID- 1900850 TI - Diagnosis and the structure of memory. 4. The power of reminding. PMID- 1900851 TI - Supraventricular tachycardia in sepsis: what mechanism? PMID- 1900852 TI - Les atomes. PMID- 1900854 TI - Acute diverticulitis: diagnosis and management. AB - A high index of suspicion is required for early detection of complications, most commonly diverticular abscess and colovesical fistula. Appropriate antibiotic therapy should cover a wide range of potential pathogens. PMID- 1900853 TI - Radiating leg pain in the older patient. AB - Failure to recognize the presentation frequently leads to misdiagnoses and treatment errors. To avoid such pitfalls, guidelines on seven prominent etiologies are provided. With careful attention to the history and physical examination, an understanding of how those etiologies present will lead to accurate diagnosis and appropriate treatment. PMID- 1900855 TI - Fever and a neck mass in a young man. PMID- 1900856 TI - Measles immunity and health care workers. PMID- 1900857 TI - Alopecia and rash in a chronically ill woman. PMID- 1900858 TI - An approach to the diagnosis of wide QRS tachycardias. PMID- 1900859 TI - New presentations of bronchiectasis. PMID- 1900861 TI - The hypercoagulable state: new knowledge, new dilemmas. PMID- 1900860 TI - A febrile infant with respiratory distress. PMID- 1900862 TI - Bisphosphonate therapy for osteoporosis. PMID- 1900863 TI - Karl Landsteiner: dissector of the blood. PMID- 1900864 TI - Abnormal guanine nucleotide regulatory protein in MVP dysautonomia: evidence from reconstitution of Gs. AB - We and others have used the term MVP dysautonomia for a particular subset of hyperadrenergic dysautonomia patients. The role of the stimulatory guanine nucleotide regulatory protein (Gs) in this dysautonomia was studied by cholate extraction of Gs from erythrocytes from 11 normal subjects and 14 symptomatic dysautonomic patients and reconstitution into cyc-S49 lymphoma membranes, which have normal receptor and adenylyl cyclase but lack Gs. Isoproterenol-stimulated adenylyl cyclase activity in the dysautonomia group was increased compared to that in controls [3.66 +/- 0.20 (mean +/- SE; n = 14) vs. 2.87 +/- 0.14 (n = 11) U cyc- reconstituted activity/mg erythrocyte protein; P less than 0.05]. beta Adrenergic receptor high affinity state formation was greatest in the severely symptomatic group [KL/KH: severe symptoms, 130 +/- 48 (n = 6); mild symptoms, 33 +/- 7 (n = 7); control, 27 +/- 6 (n = 11); severe dysautonomia distinct, P less than 0.017]. Sodium dodecyl sulfate-polyacrylamide gels of cholera toxin dependent ADP-ribosylated G-proteins yielded no gross distinction between severely symptomatic and control groups. This subset of hyperadrenergic dysautonomia patients, thus, has supercoupled beta 2-adrenergic receptors (increase in both agonist binding and cyclase activation) conferred by an abnormal Gs, whose effects on agonist binding reflect the severity of illness. PMID- 1900865 TI - Professional values and empowerment: a role for continuing education. AB - A commitment to values is increasingly important for professional nurses. For practitioners of nursing, advances in knowledge and technology are raising complicated ethical questions that need a response. The guiding of ethical decision-making is a primary function of a code of ethics such as the Code for Nurses document (1978). Among practitioners of nursing, values identified most frequently are reflected in the first six statements that deal with professional issues. Values inherent in the last five statements, which focus on social issues, such as professional empowerment, are not readily identified. Internalization of the social issue values is critical for the future of nursing. PMID- 1900867 TI - Developing case managers for chronically ill children: Florida's registered nurse specialist program. AB - This article describes the Florida Health and Rehabilitative Services/Children's Medical Services Nurse Specialist Program. This program is a statewide training and service delivery system designed to prepare selected nurses to provide comprehensive, family-centered case management services to children with special health care needs, within the home and community settings. PMID- 1900868 TI - Collaborative model for continuing education for home health nurses. AB - Nursing is at the heart of home care; therefore, the profession of nursing must ensure the availability of qualified nurses to provide and manage care in the growing and increasingly complex home care market. In response to this need, the College of Nursing, Arizona State University, developed a CE program for nurse clinicians and managers in home care. This article describes the development, implementation, and outcomes of a project that linked service agencies with education in this collaborative endeavor. PMID- 1900866 TI - Perception of "no code" and the role of the nurse. AB - CPR is now the rule rather than the exception and death is often viewed as the ultimate failure in modern medicine, rather than the final event of the natural life process (Stevens, 1986). The "No Code" concept has created a major dilemma in health care. An interagency collaborative study was conducted to ascertain the perceptions of nurses, physicians, and laypersons about this issue. This article deals primarily with the nurse's role and perceptions of the "No Code" issue. The comparison of nurses' perceptions with those of physicians and laypersons is unique to this study. Based on this research, suggestions are presented that will assist nursing educators and health care professionals in managing this complex dilemma. PMID- 1900869 TI - Experiential learning strategies for promoting positive staff attitudes toward the elderly. AB - It is generally acknowledged that American society devalues its elderly. Young people incorporate pervasive attitudes at an early age. These attitudes are later reflected in the views of health professionals. An essential component of effective care for the elderly is the attitude of the caregivers. Staff attitudes are considered important because of their presumed influence on staff behavior and the quality of care delivered. Attitude change is very difficult to achieve unless the individual is exposed to an experience that places the learning situation on a very personal level. Experiential learning activities can be tailored to provide that personal experience. If attitudes can be changed at the same time that factual information is being presented, experiential activities offer the educator a potent tool for learning. This paper suggests several such activities aimed at enhancing positive attitudes toward the elderly. PMID- 1900870 TI - Packaging yourself for success as a CNE presenter. PMID- 1900871 TI - Immunocytochemical localization of mitochondrial carbonic anhydrase in rat tissues. AB - We used a monospecific polyclonal antiserum against mitochondrial carbonic anhydrase (CA V) from rat liver to study tissue localization of this new member of the carbonic anhydrase gene family. Strong granular immunostaining reaction of CA V was observed in hepatocytes, myocardium, and in certain populations of skeletal muscle fibers. This is the first time that mitochondrial carbonic anhydrase is described in cardiac tissue of rat or any other species. Different epithelial cells revealed very heterogeneous staining reaction, suggesting that mitochondria are a heterogeneous population with respect to their CA V content. Many cells in different glandular epithelia did not show any CA V, whereas some cells, such as gastric parietal cells, were intensely stained with CA V antibodies. No systematic co-expression of CA V with CA I, CA II, or CA III was observed, although the distribution of CA V in skeletal muscle was somewhat similar to that of CA III. Connective tissue cells such as fibroblasts, chondroblasts, and osteoblasts were negative. PMID- 1900872 TI - Metabolic toxicity of fluorescent stains on thawed cryopreserved bovine sperm cells. AB - Several fluorescent probes, including derivatives of carboxyfluorescein, carbocyanine, ethidium, and rhodamine, have been used to assess sperm viability. However, the effects of these fluorescent dyes on the metabolic activity of sperm cells have not been systematically examined. This study was conducted to determine the effect of specific fluorescent stains on the metabolic processes of sperm. Cryopreserved bovine sperm cells were thawed, fluorescently stained, and examined using metabolic and flow cytometric techniques. Sperm were stained with either rhodamine 123 (Rhod-123), the aliphatic cell-tracking compound PKH2-GL, dihydro-ethidium (HED), the bisbenzimide stain Hoechst 33342 (Ho33342), or left unstained. The stained samples were compared for metabolic activity, cell staining pattern, and fluorescent intensity over a 180-min period. Samples stained with HED, Ho33342, and PKH2-GL had less oxygen uptake when compared with the unstained sperm samples (p greater than 0.05). Unstained samples and samples stained with Rhod-123 had similar oxygen consumption. The carbon dioxide produced during the 180 min was not different between controls and stained samples. Therefore, some fluorescent probes inhibit the oxygen metabolism of thawed, cryopreserved bovine sperm cells. PMID- 1900873 TI - Cross-linking of surface Ig receptors on murine B lymphocytes stimulates the expression of nuclear tetradecanoyl phorbol acetate-response element-binding proteins. AB - Cross-linking of sIg on primary B lymphocytes leads to increased nuclear DNA binding activity specific for the tetradecanoyl phorbol acetate-response element (TRE), as judged by gel mobility shift assays. Stimulation of B cells to enter S phase of the cell cycle by treatment with the combination of phorbol ester plus calcium ionophore also stimulated nuclear TRE-binding activity within 2 h, with maximal expression at 4 h; however, phorbol ester and calcium ionophore were not as effective in stimulating binding activity when examined separately. Stimulated nuclear expression of TRE-binding activity appears to require protein synthesis. Fos- and Jun/AP-1-related proteins participate directly in the identified nucleoprotein complex, as shown by the ability of c-fos- and c-jun-specific antisera to either alter or completely abolish electrophoretic migration of the complex in native gels. Further, UV photo-cross-linking studies identified two major TRE-binding protein species, whose sizes correspond to TRE-binding proteins derived from HeLa cell nuclear extracts. The results suggest that in primary B cells nuclear TRE-binding activity represents a "downstream" signaling event that occurs subsequent to changes in protein kinase C activity and intracellular Ca2+ but that can be triggered "physiologically" through sIg. PMID- 1900874 TI - Ligation of membrane Ig leads to calcium-mediated phosphorylation of the proto oncogene product, Ets-1. AB - Recent studies have demonstrated that the nuclear protein, Ets-1, which is preferentially expressed in lymphocytes, binds to the long terminal repeat of Moloney murine sarcoma virus and HTLV-1 and regulates gene expression. The association of Ets-1 with DNA has been shown to be lost when the protein is phosphorylated. Thus, Ets-1 may regulate gene expression in lymphocytes and this activity may be determined by its phosphorylation state. To address the possibility that Ets-1 activity may be altered by membrane (m) Ig-mediated signal transduction, we analyzed the effect of mIgM and mIgD ligation on the phosphorylation state of Ets-1. Monoclonal anti-IgM or anti-IgD antibody stimulation of normal mouse B cells led to increased phosphorylation of Ets-1 within 2 min. This response was absolutely dependent on calcium mobilization and could be induced by elevation of intracellular free calcium using the calcium ionophore, ionomycin. Calcium release from intracellular stores was sufficient to mediate the phosphorylation of Ets-1. Treatment of resting B cells with IL-4, TGF beta-1, IFN-gamma, anti-class I, or anti-class II antibodies did not induce Ets-1 phosphorylation. In summary, calcium mobilization from intracellular stores after mIgM or mIgD ligation provides a necessary and sufficient signal for activation of Ets-1 phosphorylation. This phosphorylation event may act in the alteration of gene expression during B cell activation. PMID- 1900875 TI - Differential susceptibility of activated macrophage cytotoxic effector reactions to the suppressive effects of transforming growth factor-beta 1. AB - We examined the effects of TGF-beta 1 on induction of several activated macrophage antimicrobial activities against the protozoan parasite Leishmania, and on induction of tumoricidal activity against the fibrosarcoma tumor target 1023. TGF-beta by itself did not affect the viability of either the intracellular or extracellular target in concentrations up to 200 ng/ml. As little as 1 ng/ml TGF-beta, however, suppressed more than 70% of the intracellular killing activity of macrophages treated with lymphokines. In contrast, more than 100 ng/ml TGF beta was required to suppress intracellular killing by cells activated with an equivalent amount of recombinant IFN-gamma. Addition of TGF-beta for up to 30 min after exposure to activation factors significantly reduced macrophage killing of intracellular parasites. Pretreatment of macrophages with TGF-beta was even more effective: treatment of cells with TGF-beta for 4 h before addition of activation factors abolished all macrophage intracellular killing activity. Regardless of treatment sequence, however, TGF-beta had absolutely no effect, at any concentration tested, on activated macrophage resistance to infection induced by lymphokines or by the cooperative interaction of IFN-gamma and IL-4. Effects of TGF-beta on tumoricidal activity of activated macrophages was intermediate to that of its effects on intracellular killing or resistance to infection. Lymphokine-induced tumor cytotoxicity was marginally (25%) affected by TGF-beta; 200 ng/ml was able to suppress IFN-gamma-induced tumoricidal activity by 40%. Thus, TGF-beta dramatically suppressed certain activated macrophage cytotoxic effector reactions, but was only partially or not at all effective against others, even when the same activation agent (IFN-gamma) was used. The biochemical target for TGF-beta suppressive activity in these reactions may be the pathway for nitric oxide production from L-arginine, because TGF-beta also inhibited the generation of nitric oxide by cytokine-activated macrophages. PMID- 1900876 TI - IFN-gamma retards the turnover of H-2Dd antigens by splenic lymphocytes. AB - The effect of IFN-gamma on the rate of shedding and biosynthesis of H-2Dd was determined by culture of cell surface-radioiodinated BALB/c spleen cells with rIFN-gamma or spleen cells metabolically labeled with 35S-methionine in the presence of IFN-gamma. Radioiodinated or 35S-labeled H-2Dd was quantitated by immunoprecipitation of H-2Dd from detergent lysates of radiolabeled cells taken at different culture intervals. The loss of 125I-labeled H-2Dd was retarded 75 to 90% by IFN-gamma whereas the biosynthetic rate was unaffected during the first 10 h culture. The net result was a ninefold increase in newly synthesized cell associated H-2Dd. The results were consistent with determination of the kinetics of increased expression of H-2Dd determined by immunofluorescence and suggest that an early effect of IFN-gamma on the expression of class I Ag is a retardation of catabolism leading to an increase of newly synthesized class I Ag. PMID- 1900877 TI - In vivo response of secretory component in the rat uterus to antigen, IFN-gamma, and estradiol. AB - Intrauterine immunization of ovariectomized rats with SRBC is known to elicit pronounced IgA and IgG antibody responses in uterine secretions of immunized uteri. To determine whether secretory component (SC), the receptor for transporting polymeric IgA from tissues to mucosal surfaces, was also influenced by Ag, ovariectomized rats were immunized and boosted by placing SRBC into the lumena of individual uterine horns. In response to Ag, the levels of polymeric IgA, as well as free SC and SC bound to polymeric IgA, increased in uterine secretions. When ovariectomized animals were treated with estradiol, a fivefold increase in SC levels was observed in the immunized horns, indicating that a hormone response is superimposed on the Ag-induced stimulation of uterine SC. To determine whether IFN-gamma influences the presence of SC in uterine secretions, IFN-gamma was placed in the uterine lumena of ovariectomized nonimmunized rats. When uterine secretions were analyzed, significantly higher levels of SC were found in IFN-gamma-exposed uteri than were present in saline treated control animals. In contrast, intrauterine instillation of IFN-gamma had no effect on the levels of IgA in uterine secretions. This response was specific for IFN-gamma in that IFN-alpha/beta had no effect on uterine SC or IgA levels. These results indicate that intrauterine instillation of Ag, in addition to evoking pronounced antibody responses, stimulates the production of SC, which may be responsible for the transport of polymeric IgA from tissue to uterine secretions. Furthermore, they indicate that IFN-gamma placed in the uterine lumen stimulates SC production and suggest that the uterine SC response to Ag may be mediated by the action of IFN-gamma on uterine epithelial cells. PMID- 1900878 TI - Antigenicity and immunogenicity of a multiple peptidic construction of the Schistosoma mansoni Sm-28 GST antigen in rat, mouse, and monkey. 1. Partial protection of Fischer rat after active immunization. AB - Among the schistosome proteins characterized as vaccine candidates, an Ag of 28 kDa (Sm-28-GST) has received considerable attention. It was shown to be antigenic in humans and protective in mice, rats, hamsters, and baboons. Synthetic peptides derived from its sequence have been used to characterize the immune response to the molecule and one of these, comprising aminoacids 115-131 has been shown to incorporate both T and B cell recognition sites in a variety of experimental models. An octameric ("octopus") construction of the 115-131 peptide has been synthesized and its antigenicity and immunogenicity have been examined. The octopus construct is immunogenic in rats, mice and baboons in the presence of CFA (for rodents) and Bacille-Calmette-Guerin vaccine (for primates) as adjuvants. This clearly indicates that the construction allowed the conservation of the immune sites of the cognate protein. Moreover, anti-octopus sera from immunized Fischer rats were able to mediate platelet-, macrophage-, and eosinophil dependent cytotoxicity toward schistosomula. Rats immunized with the 115-131 octopus were partially protected against a challenge infection with Schistosoma mansoni cercariae and this was paralleled by an increased level of IgG and more importantly, of IgE Sm-28-GST-specific antibodies. PMID- 1900879 TI - Two induced anti-Z-DNA monoclonal antibodies use VH gene segments related to those of anti-DNA autoantibodies. AB - The cDNA for H and L chain V regions of two anti-Z-DNA mAb, Z22 and Z44, were cloned and sequenced. These are the first experimentally induced anti-nucleic acid antibody sequences available for comparison with autoantibody sequences. Z22 and Z44 are IgG2b and IgG2a antibodies from C57BL/6 mice. They recognize different facets of the Z-DNA structure. They both use VH10 family genes and share 95% sequence base sequence identity in the VH and leader sequences; however, they differ in the 5'-untranslated region of the VH mRNA, indicating they arise from different germline genes. Both use JH4 segments. They differ from each other very extensively in the CDR3 of both H and L chains. The most closely related H chains in the current GenBank/EMBL data base are two mouse IgG anti-DNA autoantibodies, one from an MRL-lpr/lpr mouse (MRL-DNA4) and one from an NZB/NZW mouse (BV04-01). Z22 and Z44 share 95% sequence identity with these antibodies in the VH segment. In addition, Z22 is identical to MRL-DNA4 at 91% of the positions in the 5'-untranslated region of the H chain mRNA. The two antibodies share 95% base sequence identity in the V kappa segment. The most closely related L chains, with 97 to 98% sequence identity, are the V kappa 10b germline gene for Z22 and the V kappa 10a germ line gene, which is associated with A/J anti-arsonate antibodies and BALB/c anti-ABO blood group substance antibodies, for Z44. Z22 and Z44 share several structural features (similarities in VH, JH, and V kappa) but differ very markedly in the L chain CDR1 and both H and L chain CDR3 sequences; these regions may determine the differences in their specific interactions with Z DNA. PMID- 1900880 TI - Latent a1 VH germline genes in an a2a2 rabbit. Evidence for gene conversion at both the germline and somatic levels. AB - We have previously reported the sequences of putative latent a1 cDNA derived from an alpha 2 alpha 2 rabbit. Significant similarity to nominal a1 cDNA sequences was noted, but none of the latent sequences were completely a1-like. We have now probed a genomic library, produced from the same alpha 2 alpha 2 rabbit, for evidence of germline latent a1 VH genes. Four hundred ninety-four VH+ clones were screened with oligonucleotides specific for a1 diagnostic regions of framework region 1 (FR1) and FR3. Twenty-two percent of the VH+ clones hybridized with an a1FR3 oligonucleotide probe. Two a1 FR1 probes yielded weak signals with 6% to 13% of the VH+ clones. Twenty VH genes from clones positive for one or more of the a1-specific oligonucleotide probes were sequenced, revealing 14 unique germline VH genes. All but one of these genes were 85% to 92% identical to the VH1-a1 nominal gene prototype, with sequence identity extending into the leader intron. Most genes displayed extended regions of similarity to a1 in FR1, FR3, or both and expressed 13 to 17 of the 21 allotype-associated residues, consistent with the nominal a1 sequence. The a1-like sequences were variously interspersed with short non-a1 segments, suggestive of germline gene conversion. Although none of the germline a1-like VH genes we have isolated from the alpha 2 alpha 2 rabbits are identical to the known a1 genes or protein sequences from alpha 1 alpha 1 rabbits and 8 of 14 are pseudogenes, most could make significant contributions to the synthesis of a complete nominal a1 sequence by serving as a pool of sequence donors during somatic gene conversion. PMID- 1900881 TI - T-dependent destruction of thyroid isografts exposed to IFN-gamma. AB - Several autoimmune diseases are accompanied by tissue-specific expression of class II molecules of the MHC, and it has been suggested that this elicits a T cell response against tissue-specific Ag to which the individual is not tolerant. However, recent transgenic studies have indicated that non-lymphoid expression of class II genes in the pancreas, liver, and kidney is either innocuous or induces peripheral tolerance. To test this hypothesis in another organ-specific autoimmune disease, we attempted to induce autoimmune thyroiditis in normal mice with class II+ thyroid tissue. Normal thyroid lobes were cultured with and without IFN-gamma and then transplanted to adult isogeneic recipients. The thyroid that had been induced to express class II genes by IFN-gamma was destroyed in normal mice, whereas the control cultured thyroid and the native cervical gland survived. Both types of transplants remained intact and functional in congenic nu/nu recipients, indicating that neither exposure to IFN-gamma nor expression of class II genes compromised the thyroid. Thus, in some tissues, exposure to IFN-gamma and/or the induction of class II expression can lead to T dependent autoimmune disease. PMID- 1900882 TI - The role of IL-4 in proliferation and differentiation of human natural killer cells. Study of an IL-4-dependent versus an IL-2-dependent natural killer cell clone. AB - The role of IL-4 in proliferation and differentiation of human NK cells was studied using newly established sublines of an IL-4-dependent NK cell clone (IL4d NK cells) and an IL-2-dependent NK cell clone (IL2d-NK cells) derived from a parental conditioned medium-dependent NK cell clone (CM-NK cells). IL-4 induced the higher proliferation of CM-NK cells, but abolished their NK activity and decreased CD16 and CD56 Ag expression. In contrast, IL-2 induced the higher NK activity and increased CD16 and CD56 Ag expression. Addition of anti-IL-4 antibody to the culture of CM-NK cells with CM inhibited the proliferation, but slightly increased NK activity, and largely increased CD56 Ag expression. Addition of anti-IL-2 antibody to the culture of CM-NK cells with CM inhibited both proliferation and cytotoxicity. Proliferation of IL4d-NK cells, which is totally dependent on rIL-4, is greater than that of IL2d-NK cells, which was greater than parental CM-NK cells. Morphologically, IL4d-NK cells are small and round, whereas IL2d-NK cells are large and elongated. Anti-IL-4 antibody inhibited proliferation of IL4d-NK but not IL2d-NK cells, whereas anti-IL-2 antibody inhibited that of IL2d-NK but not IL4d-NK cells. IL-2 was not detected in the supernatant from IL4d-NK cells, nor was IL-2-mRNA expressed in IL4d-NK cells. In contrast, IFN-gamma production and protein expression in IL4d- and IL2d NK cells were detected. NK cell activation markers (CD16 and CD56) were expressed on IL2d-NK cells but not IL4d-NK cells. IL4d-NK cells were not cytotoxic to any tumor cells tested, whereas IL2d-NK cells displayed potent NK activity and lymphokine-activated killer activity. IL4d-NK cells failed to bind K562 tumor cells, whereas one-third of the IL2d-NK cells did. IL4d-NK cells responded to rIL 2, proliferated, and differentiated into cytotoxic NK cells, whereas IL2d-NK cells failed to respond to rIL-4 and died. These results raise a possibility that IL4d-NK cells or IL2d-NK cells primarily represent the immunologic properties of immature or activated types of human NK cells, respectively. Our results provide the first evidence of the capability of IL-4 to support continuous proliferation of a lymphocyte clone with immature NK cell characteristics and to stimulate IFN gamma production in the clone. IL-4 is suggested as a potential growth factor for certain types of human NK cell progenitors. PMID- 1900883 TI - The endocrine significance of cytokines. PMID- 1900884 TI - Developmental analysis of the facets, a group of intronic mutations at the Notch locus of Drosophila melanogaster that affect postembryonic development. AB - The activity of the Notch locus of Drosophila melanogaster during embryogenesis is necessary for the correct segregation of neural from epidermal lineages. The action of Notch is not confined to embryogenesis but is also essential for normal development during the postembryonic stages. Its action is pleiotropic, as revealed by the existence of several classes of mutations which affect various imaginal structures. Here, we examine a group of six recessive mutations, the facets (fa, fa3, fag, fag-2, fafx and fasw), which affect eye and optic lobe morphology and have been previously shown to be associated with the insertion of transposable elements into an intronic region of Notch. Using both somatic recombination and gynandromorph analysis, we find that their behavior in a mosaic analysis is not identical. While in the majority of alleles abnormal Notch function in the retina is sufficient to induce optic lobe abnormalities, in the case of fag-2, a considerable number of individuals having mosaic retinas exhibit normal optic lobe structure. All the facet alleles appear to behave in a cell autonomous manner. A developmental analysis of the eye and optic lobe defects associated with the facet mutations support the contention that Notch may be involved not only in the formation of certain structures but also in their maintenance. PMID- 1900885 TI - B95a, a marmoset lymphoblastoid cell line, as a sensitive host for rinderpest virus. AB - We reported earlier that B95a, an Epstein-Barr virus-transformed marmoset B lymphoblastoid cell line, is more susceptible to infection with measles virus than other cells. The cell line also was found to be susceptible to infection with the lapinized Nakamura III (L) strain of rinderpest virus and various strains derived from it. The B95a cell line was therefore the only host cell system available for the propagation and quantification of the L strain. In contrast to the adaptation of the L strain to Vero cells which results in a diminution of virulence in rabbits, the propagation of the virus in B95a cells preserved the virulence and some other properties in rabbits. Furthermore, when Vero cell-adapted variants of the L strain with diminished virulence were serially passaged in B95a cells, virulence in rabbits was gradually regained. PMID- 1900887 TI - Absent splenic uptake of indium-111-oxine-labeled autologous leukocytes in functional asplenia. AB - An incidental finding of absent splenic uptake of autologous, indium-111-oxine labeled leukocytes in an immunosuppressed renal transplant recipient was documented to be associated with functional asplenia based on absence of technetium-99m-sulfur colloid clearance by a morphologically normal spleen. The patient had recently suffered an episode of disseminated varicella infection that might have led to the development of functional asplenia. PMID- 1900886 TI - Rapid localization of indium-111-labeled inhibited recombinant tissue plasminogen activator in a rabbit thrombosis model. AB - The thrombus localizing properties of indium-111-recombinant tissue plasminogen activator (111In-rt-PA) have been investigated in an effort to achieve prompt and accurate detection of thrombi. Unlike previous studies with rt-PA, the active plasminogen catalytic site was permanently inhibited with peptides of chloromethyl ketone so that the radiotracer binds to fibrin without causing fibrinolysis. Thrombi were created in the external jugular vein of 14 male New Zealand white rabbits followed by injection of 111In-rt-PA. The agent cleared rapidly in vivo with a half-time of 4.6 min. The thrombus: blood ratio in nonheparinized rabbits (n = 7) was 6.39 +/- 0.86. The ratio in heparinized rabbits (n = 4) was 3.11 +/- 0.23. Thrombi were clearly visible in the planar images of both groups 1 hr postinjection. The combination of rapid thrombus localization and positive images, especially in the presence of anticoagulation, suggests that further work is warranted with rt-PA thrombus imaging. PMID- 1900888 TI - Technique for splanchnic transplantation. AB - The combination of short-bowel syndrome and liver failure in infancy is inevitably fatal. We describe the details of a technique for simultaneous implantation of both the bowel and the liver that leaves the native bowel undisturbed and avoids entering the gastrointestinal tract. The conceptual basis on which this procedure was performed in two infants is presented. PMID- 1900889 TI - Calcified thrombus in the right atrium: a rare complication of long-term parenteral nutrition in a child. AB - A 5-year-old boy with short-bowel syndrome who receives home parenteral nutrition developed a calcified thrombus that involved the inferior vena cava (IVC) and the right atrium. Symptoms included 3 to 4 months of intermittent fever and 2 months of vague chest pain. Blood could not be aspirated from the IVC catheter and an IVC contrast study demonstrated the calcified thrombus. The intracardiac portion of the mass was removed surgically, but the IVC mass could not be completely excised. The boy developed a pericardial effusion 6 weeks after surgery. He was treated for this and 6 months after the initial surgery the patient was asymptomatic. PMID- 1900890 TI - The role of prostaglandin synthetase in the rate depressant effects and narcosis caused by ethanol. AB - Ethanol is proposed to exert its pharmacological effects by increasing membrane fluidity. Support for this hypothesis comes from strong correlations between in vitro effects of ethanol and pharmacological effects and genetic variation seen in vivo. Because arachidonate acid (AA) cascade is a membrane-bound system activated by disruptions in the cell membrane, it is possible that ethanol induced membrane fluidization increases the formation of AA metabolites such as prostaglandins. The studies reported here were designed to characterize systematically the ability of various prostaglandin endoperoxide synthetase (PES; prostaglandin synthetase or cyclooxygenase) inhibitors to antagonize the effects of ethanol. A wide range of chemically diverse PES inhibitors significantly antagonized the rate-depressant effects and acute narcosis caused by ethanol. The ability of these compounds to antagonize the effects of ethanol was significantly correlated with two measures of PES activity; in vitro inhibition of the PES enzyme and in vivo anti-inflammatory activity. These significant potency correlations between the ability of PES inhibitors to antagonize in vivo acute ethanol hypnosis and their ability to inhibit in vitro and in vivo conversion of AA to AA metabolites strongly suggest an underlying functional relationship. These results obtained from two divergent dependent measures of the effects of ethanol, duration of loss of the righting reflex and rate depressant effects, extend the range of ethanol-related behaviors that PES inhibitors effectively antagonize and provide substantive evidence in support of a mechanistic role for PES and related metabolites in the central effects of ethanol. PMID- 1900891 TI - Meeting the mental health needs of elderly clients. AB - 1. Older individuals in both community and institutional settings have traditionally underused mental health services. Providers of such care devote a minimum of their professional time to those over 65 years of age. 2. Ageism and difficulty with diagnosis are the most frequent explanations for inadequate mental health care to the elderly. This study found that lack of referrals and failure of the aged to seek services partially accounted for underuse. 3. Legislative changes mandating that aged persons be screened for and receive appropriate mental health services will increase the demand for qualified providers. 4. Nursing's approach to care of the older adult, which focuses on both physiological and psychological needs, can facilitate the delivery of comprehensive effective mental health interventions in and out of the institutional setting. PMID- 1900892 TI - Bovine spongiform encephalopathy. AB - Two years after the introduction of a slaughter policy for BSE, the author summarizes the development of the epidemic and introduction of Government controls. In conclusion, the risk to humans is discussed. PMID- 1900893 TI - Stromal osseous metaplasia in carcinoma of the bladder. AB - Osseous metaplasia of the stroma of carcinomas of the bladder is a rare finding that must be distinguished from osteosarcoma and carcinosarcoma. We report a case of multifocal osseous metaplasia in a high grade urothelial carcinoma with extensive glandular differentiation, arising in the base of the bladder of an 84 year-old man. Reports of 11 other cases of stromal osseous metaplasia in primary bladder carcinomas and of 5 cases of stromal osseous metaplasia in metastases of bladder carcinoma are reviewed. PMID- 1900894 TI - Analyzing hospital mortality. The consequences of diversity in patient mix. AB - Consumers and payers increasingly demand data with which to evaluate health care providers. While publication of risk-adjusted hospital-specific death rates is one response, debate continues over whether higher than predicted mortality is a warning about quality of care or rather a reflection of a hospital's atypical patient population. To help inform this debate, we compared the characteristics of Medicare patients discharged from 187 hospitals that the Health Care Financing Administration (HCFA) had labeled "high-mortality outliers" with those of Medicare patients from 5373 hospitals not so designated. Hospitals were most likely to be flagged as high-mortality outliers by HCFA when they had large shares of very elderly patients (age greater than or equal to 85 years), patients with high-risk diagnoses, or patients requiring nursing home care. After adjustments were made to compensate for these biases, nearly half the hospitals flagged as outliers by HCFA were no longer so designated. Statistics purporting to measure effectiveness of care from hospital death rates should be modified to account for diversity in patient mix. PMID- 1900895 TI - Ethical aspects of human experimentation in health services research. PMID- 1900896 TI - Commitment to patient education. PMID- 1900897 TI - The practicing nurse as leader. PMID- 1900898 TI - Choosing to make a difference. PMID- 1900899 TI - Launching a leadership role. PMID- 1900900 TI - The bedside nurse: nursing's grass-roots leader. PMID- 1900901 TI - The leader in nursing research. PMID- 1900902 TI - The scope of leadership opportunities. PMID- 1900903 TI - The quest for leadership. PMID- 1900904 TI - Winds of autonomy. PMID- 1900906 TI - Major legal initiatives in MCH (1975-1990). PMID- 1900907 TI - An overview of maternal-child infectious diseases (1976-1990). PMID- 1900905 TI - Quantitative and qualitative research methods: advantages of complementary usage. PMID- 1900908 TI - Home care for preterm birth prevention: is nursing monitoring the interventions? PMID- 1900909 TI - On the optimization of cholesterol screening. AB - Total serum cholesterol is a major risk factor for Coronary Heart Disease (CHD). Some guidelines have been published regarding treatment levels. However, before implementing cholesterol screening, the costs and benefits should be analyzed as a function of cholesterol level. Analysis is readily implemented on microcomputer spreadsheets using decision tree analysis. Because it is very difficult to establish some of the costs satisfactorily, the facility of spreadsheets in performing sensitivity analysis is crucial. Here, plausible numerical values are used as "default" conditions for estimating in a preliminary way the costs and benefits of a putative screening-intervention program. The cost-benefit condition remains very close to optimal over the range 200-240 mg/dl for cholesterol marker level. The optimal condition may shift considerably when the default parameter values are altered. With the default values, the maximal net benefit is around 5% of the estimated current costs of CHD deaths without screening. PMID- 1900911 TI - Outbreak of pellagra among Mozambican refugees--Malawi, 1990. AB - Micronutrient deficiency disorders, including pellagra, have emerged as major problems in refugee populations that depend on international relief assistance for food supplies. This report summarizes an investigation of pellagra that occurred among Mozambican refugees in Malawi during 1990. PMID- 1900910 TI - Long-term antiplatelet therapy for the prevention of vascular disease. AB - OBJECTIVE: To estimate the effects of prolonged antiplatelet therapy on the primary and secondary incidence of vascular disease. DATA SOURCES: Twenty-five randomised trials in 29,000 patients with a history of vascular disease (the Antiplatelet Trialists' Collaboration) and two randomised trials in 27,000 individuals without a history of vascular disease (the British doctors' and American physicians' studies). STUDY SELECTION: The Antiplatelet Trialists' Collaboration obtained data from all randomised trials of secondary prevention completed before January 1988. The British doctors' and American physicians' studies are the only two completed randomised trials of primary prevention. DATA EXTRACTION: Data from the secondary prevention trials were provided by the Antiplatelet Trialists' Collaboration. Data from the primary prevention trials were extracted from the final published reports of these studies. DATA SYNTHESIS: In the secondary prevention trials, antiplatelet therapy reduced the rate of vascular disease by about 15% and the incidence of non-fatal myocardial infarction and stroke by about 30%. In the American physicians' study, but not the British doctors' study, the incidence of non-fatal myocardial infarction was also reduced. In neither primary prevention trial was there evidence of reduced rates of non-fatal stroke or vascular death; overall, fatal or disabling strokes were slightly more frequent among those assigned aspirin. CONCLUSIONS: For patients with a history of vascular disease, the benefits of antiplatelet therapy appear to outweigh any risks. Among 100 such patients, antiplatelet therapy for two years would prevent one death and two major non-fatal events. The balance of benefits and risks for individuals without a history of vascular disease is less clear because there is no firm evidence of a net reduction in either vascular death or disabling non-fatal vascular events among those treated with aspirin. PMID- 1900912 TI - AIDS-related knowledge and behaviors among teenagers--Italy, 1990. AB - As of December 31, 1990, the number of acquired immunodeficiency syndrome (AIDS) cases in Italy exceeded 8000. Although 67% of AIDS cases in Italy occurred among intravenous (IV)-drug users, the role of transmission through heterosexual contact with human immunodeficiency virus (HIV)-infected persons has increased, accounting for 7% of cases in 1990, compared with 2% in 1985. As part of an AIDS epidemiology course in Frascati for regional AIDS epidemiologists (approximately 20 km [13 miles] south of Rome) in November 1990, course participants surveyed AIDS-related knowledge and behaviors among students attending the five high schools in the local school district. This report summarizes findings of the survey, which aimed to characterize AIDS-related knowledge and behaviors of this population. PMID- 1900913 TI - Nutritional assessment of children in drought-affected areas--Haiti, 1990. AB - From January through June 1990, a drought occurred in the Caribbean nation of Haiti. To determine whether the nutritional status of young children had been affected by drought-related reductions in food supply, in September 1990 a nutrition survey was conducted in the five departments most affected (Nord-Ouest, Nord, Nord-Est, Artibonite, and Centre) of Haiti's nine departments. PMID- 1900914 TI - Update: cholera outbreak--Peru, Ecuador, and Colombia. PMID- 1900915 TI - Cloning, characterization and expression of an alpha-amylase gene from Streptomyces griseus IMRU3570. AB - A gene, amy, encoding an alpha-amylase, was cloned on a 4.8 kb Sau3A fragment from the DNA of Streptomyces griseus IMRU3570. The gene was localized to a 2.27 kb fragment by subcloning and deletion mapping experiments. The gene contained an open reading frame (ORF) of 1698 nucleotides that encoded a protein of 566 amino acids with a deduced Mr of 59713 Da. Dot-blot analysis revealed that the copy number of the transcript in S. lividans transformed with the amy gene was 2.8 fold higher than in the donor S. griseus strain in good agreement with the proportionally higher secretion of amylase in S. lividans. A transcription initiation site was found approximately 64 bp upstream from the ATG translation start codon. The promoter of the amy gene was subcloned on a 290 bp HindIII- EcoRI fragment. Expression of a neomycin resistance gene from the amy promoter was negatively regulated by glucose. A 219 nucleotide fragment extending from the single BstEII site to the end of the amy gene was dispensable since active alpha amylase was secreted after deletion of this region and coupling of a TGA translation stop codon. PMID- 1900916 TI - Identification and organization of carbon dioxide fixation genes in Xanthobacter flavus H4-14. AB - The genes encoding the large (cfxL) and small (cfxS) subunits of ribulose-1,5 bisphosphate carboxylase (RuBisC/O) from Xanthobacter flavus H4-14 were identified and characterized. The RuBisC/O genes are separated by 11 bp and cotranscribed in Escherichia coli from the lac promoter in the order cfxLS. Primer extension and R-loop experiments with RNA isolated from autotrophically grown X. flavus H4-14 showed that transcription of cfxL and cfxS initiated 22 bp upstream from cfxL and resulted in a mRNA of at least 2.3 kb. DNA sequence analysis identified the start of an open reading frame transcribed divergently from cfxL, and displaying significant similarities with genes belonging to the lysR family of transcriptional activators. Downstream from cfxS an additional open reading frame was identified with unknown function. Expression studies showed that the genes encoding fructosebisphosphatase (cfxF) and phosphoribulokinase (cfxP) are located downstream from cfxLS. The cfxF and cfxP genes are cotranscribed in the same direction as cfxLS in the order cfxFP. PMID- 1900917 TI - DNase I-hypersensitive sites and transcription factor-binding motifs within the mouse E beta meiotic recombination hot spot. AB - The second intron of the E beta gene in the mouse major histocompatibility complex is the site of a meiotic recombination hot spot. We detected two DNase I hypersensitive sites in this intron in meiotic cells isolated from mouse testes. One site appears to be constitutive and is found in other tissues regardless of whether or not they express the E beta gene. Near this hypersensitive site are potential binding motifs for H2TF1/KBF1, NF kappa B, and octamer transcription factors. Gel retardation studies with mouse lymphoma cell nuclear extracts confirmed that each of these motifs is capable of binding protein. The binding of transcription factors may contribute to the enhancement of recombination potential by altering chromatin structure and increasing the accessibility of the DNA to the recombination machinery. PMID- 1900918 TI - Characterization of the BCR promoter in Philadelphia chromosome-positive and negative cell lines. AB - The t(9;22) Philadelphia chromosome translocation fuses 5' regulatory and coding sequences of the BCR gene to the c-ABL proto-oncogene. This results in the formation of hybrid BCR-ABL mRNAs and proteins. The shift in ABL transcriptional control to the BCR promoter may play a role in cellular transformation mediated by this rearrangement. We have functionally localized the BCR promoter to a region 1 kb 5' of BCR exon 1 coding sequences by using a chloramphenicol acetyltransferase reporter gene assay. Nucleotide sequence analysis of this region revealed many consensus binding sequences for transcription factor SP1 as well as two potential CCAAT box binding factor sites and one putative helix-loop helix transcription factor binding site. No TATA-like or "initiator" element sequences were found. Because of low steady-state levels of BCR mRNA and the high GC content (78%) of the promoter region, definitive mapping of transcription start sites required artificial amplification of BCR promoter-directed transcripts. Overexpression from the BCR promoter in a COS cell system was effective in demonstrating multiple transcription initiation sites. In order to assess the effects of chromosomal translocation on the transcriptional control of the BCR gene, we determined S1 nuclease protection patterns of poly(A)+ RNA from tumor cell lines. No differences were observed in the locations and levels of BCR transcription initiation sites between those lines that harbored the t(9;22) translocation and those that did not. This demonstrates that BCR promoter function remains intact in spite of genomic rearrangement. The BCR promoter is structurally similar to the ABL promoters. Together, this suggests that the structural fusion of BCR-ABL and not its transcriptional deregulation is primarily responsible for the transforming effect of the t(9;22) translocation. PMID- 1900919 TI - Repression of hsp70 heat shock gene transcription by the suppressor of hairy-wing protein of Drosophila melanogaster. AB - The suppressor of hairy-wing [su(Hw)] locus of Drosophila melanogaster encodes a zinc finger protein that binds a repeated motif in the gypsy retroposon. Mutations of su(Hw) suppress the phenotypes associated with mutations caused by gypsy insertions. To examine the mechanisms by which su(Hw) alters gene expression, a fragment of gypsy containing multiple su(Hw) protein-binding sites was inserted into various locations in the well-characterized Drosophila hsp70 heat shock gene promoter. We found no evidence for activation of basal hsp70 transcription by su(Hw) protein in cultured Drosophila cells but observed that it can repress heat shock-induced transcription. Repression occurred only when su(Hw) protein-binding sites were positioned between binding sites for proteins required for heat shock transcription. We propose that su(Hw) protein interferes nonspecifically with protein-protein interactions required for heat shock transcription, perhaps sterically, or by altering the ability of DNA to bend or twist. PMID- 1900920 TI - Coordination of immunoglobulin DJH transcription and D-to-JH rearrangement by promoter-enhancer approximation. AB - The genes that encode the variable regions of immunoglobulin (Ig) heavy chains are encoded by three DNA segments: VH, D, and JH. During B-cell development these segments are brought together by a pair of site-specific DNA rearrangements. The first of these joins a D segment to a JH segment; the second brings a VH segment in apposition to a DJH unit. B-cell precursors that have undergone D-to-JH joining express transcripts that initiate at the 5' flanks of rearranged D segments (DJH transcription). In this study we have examined the coordination of D-to-JH rearrangement and DJH transcription. The B-lymphoid progenitor cell line HAFTL-1 cell clone, joining of distal D segments (DSP2 and DFL16) to JH is accompanied by an increase in the steady-state level of transcripts initiating 5' of the D coding region. Steady-state transcription of a DSP2 gene segment was undetectable prior to rearrangement and was observed to increase at least 20-fold upon joining to JH. In contrast, transcription from the 5' flank of DQ52, which lies within 700 bp of the JH cluster, was detected prior to rearrangement and did not increase significantly after rearrangement. The 5' flank of a DSP2 segment was found to support expression of a heterologous gene upon transfection into B progenitor cell lines. Expression from this DSP2 promoter was at least 30-fold higher in the presence of the Ig heavy-chain enhancer, in either orientation, than in its absence. A DNA fragment spanning the interval from -165 to +19 bp relative to the major DSP2 transcriptional start site retained enhancer-dependent promoter activity. These observations imply that activation of DSP12JH and DFL16JH transcription is coordinated with D-to-JH rearrangement by approximation of enhancer-dependent D promoter elements to the Ig heavy-chain enhancer. This interpretation is consistent with our observation that the DQ52 segment, which is closely linked to the JH cluster, is transcribed both before and after rearrangement. PMID- 1900921 TI - Translation initiation in Drosophila melanogaster is reduced by mutations upstream of the AUG initiator codon. AB - The importance to in vivo translation of sequences immediately upstream of the Drosophila alcohol dehydrogenase (Adh) start codon was examined at two developmental stages. Mutations were introduced into the Adh gene in vitro, and the mutant gene was inserted into the genome via germ line transformation. An A to-T substitution at the -3 position did not affect relative translation rates of the ADH protein at the second-instar larval stage but resulted in a 2.4-fold drop in translation of ADH at the adult stage. A second mutant gene, containing five mutations in the region -1 to -9, was designed to completely block translation initiation. However, transformant lines bearing these mutations still exhibit detectable ADH, albeit at substantially reduced levels. The average fold reduction at the second-instar larval stage was 5.9, while at the adult stage a 12.5-fold reduction was observed. PMID- 1900923 TI - Genome project. PMID- 1900924 TI - Origins of AIDS. PMID- 1900922 TI - Autonomous DNA replication in human cells is affected by the size and the source of the DNA. AB - We previously developed short-term and long-term assays for autonomous replication of DNA in human cells. This study addresses the requirements for replication in these assays. Sixty-two random human genomic fragments ranging in size from 1 to 21 kb were cloned in a prokaryotic vector and tested for their replication ability in the short-term assay. We found a positive correlation between replication strength and fragment length, indicating that large size is favored for efficient autonomous replication in human cells. All large fragments replicated efficiently, suggesting that signals which can direct the initiation of DNA replication in human cells are either very abundant or have a low degree of sequence specificity. Similar results were obtained in the long-term assay. We also used the same assays to test in human cells a random series of fragments derived from Escherichia coli chromosomal DNA. The bacterial fragments supported replication less efficiently than the human fragments in the short-term and long term assays. This result suggests that while the sequence signals involved in replication in human cells are found frequently in human DNA, they are uncommon in bacterial DNA. PMID- 1900925 TI - Abnormal tau-reactive filaments in olfactory mucosa in biopsy specimens of patients with probable Alzheimer's disease. AB - We immunocytochemically analyzed pieces of olfactory mucosa removed by biopsy in 8 patients with probable Alzheimer's disease (AD) and 6 age-matched controls, with tau and ubiquitin antisera. There were tau-reactive and, partially, ubiquitin-reactive dystrophic neurites in the lamina propria of olfactory mucosa in all AD cases. The tau-reactive neurites contained abnormal straight filaments, 15 to 18 nm in diameter, morphologically identical to those found in AD cerebral brain tissue obtained at autopsy. Tau and ubiquitin immunoreactivity were absent in controls. If these neuritic alterations are confirmed in a larger number of cases, analysis of olfactory mucosa may increase the current reliability of clinical diagnosis of AD. PMID- 1900926 TI - Endometriosis of the rectum treated with a long term GnRH agonist and surgery. PMID- 1900927 TI - Health economics: a framework for health service decision-making. PMID- 1900928 TI - Quality assessment in support services: do practitioners concur with expert consensus? AB - The purpose of this study was to examine the degree of concordance between experts and practitioners as to the importance of quality assessment measures (elements and indicators) in therapeutic recreation (TR) services. Results from a survey of TR practitioners as to actual uses of these quality assessment measures within Veterans Affairs Recreation Services nationwide were compared to expert opinions used in a previous study that identified quality assessment measures for TR. Agreement between expert ratings of importance and frequency of use by practitioners were greatest for the experts' most important elements and indicators and least for the least important. Findings suggest that a select few "important" elements and indicators might be universally required of all quality assessment programs; others might be optional or can be modified to meet the needs of individual settings. Results also demonstrate the need for further study of optimal quality assessment approaches using both expert knowledge and practitioner experience. PMID- 1900929 TI - Managing negative outcome by reducing variances in the emergency department. AB - Negative outcome management depends upon reducing variances in the structure and process of health care. In the multitask environment of a hospital's emergency department (ED), a system is required to monitor the many tasks for variances. Without a monitoring system in place, the cumulative effect of these structure and process variances will significantly contribute to negative outcomes. Structure and process variance management requires a customer-focused, process conceptualization approach that attempts to manage the many small variances in care along the entire chain of interdependent processes making up the ED system. Process mapping is one technique that enables management to understand and anticipate variances and take corrective action to eliminate them before they occur. PMID- 1900930 TI - Reducing restraint use in nursing homes: the governing board's role. PMID- 1900931 TI - Women and drug users: the changing faces of HIV clinical drug trials. PMID- 1900932 TI - CQI--a step beyond QA. PMID- 1900933 TI - Reply to "Quality assurance: a myth?". PMID- 1900934 TI - Medicare: a strategy for quality assurance, I: A recapitulation of the study and a definition of quality of care. AB - The first of a series of articles on the Institute of Medicine study on a quality review and assurance program for Medicare, this article reviews the findings, conclusions, and recommendations of the IOM study committee and discusses the quality-of-care definition, which became a focal point for the report. A QA system should achieve a balance among important dimensions of "quality of care;" several such dimensions were identified. Turning the definition into practical measurement and intervention approaches and implementing a QA strategy based on it remain significant challenges. PMID- 1900935 TI - Are we giving value for money? PMID- 1900936 TI - A second maternally expressed Drosophila gene encodes a putative RNA helicase of the "DEAD box" family. AB - Recently, a family of proteins containing the conserved motif Asp-Glu-Ala-Asp, the "DEAD box" proteins, has been identified. This family is typified by the eukaryotic translation initiation factor eIF4A, and its members are believed to share the functional property of ATP-dependent RNA unwinding. One of the previously identified members of this family (vasa) is the product of a maternally expressed gene from Drosophila melanogaster that is known to play a role in the formation of the embryonic body plan. We report here the isolation of a Drosophila gene that has an mRNA expression pattern somewhat similar to that of vasa and also encodes a DEAD box protein. We have termed this gene ME31B to reflect its maternal (ovarian germ-line) expression and its location within the 31B chromosome region. Comparisons with the other members of this family reveal that although ME31B is most like the protein Tif1/Tif2, which probably represents the Saccharomyces cerevisiae version of eIF4A, it is unlikely that ME31B represents the Drosophila eIF4A protein per se. A search for mutations in the ME31B gene has established that the P element which causes the female-sterile mutation flipper lies in the 3' flank of the ME31B gene. PMID- 1900937 TI - Laventiana annectens, new genus and species: fossil evidence for the origins of callitrichine New World monkeys. AB - A previously unidentified middle Miocene primate from the La Venta deposits of Colombia is intermediate between squirrel monkeys (Saimiri) and callitrichines (marmosets and tamarins) in the morphology of the lower molars, mandible, and talus. Laventiana annectens is closely related to Saimiri and to Cebus (capuchin monkeys) yet resembles the probable callitrichine morphotype, demonstrating that archaic relatives of a Saimiri-like stock were suitable structural ancestors for the enigmatic callitrichines. Laventiana is also more primitive than Saimiri (= Neosaimiri) fieldsi from the same fauna, further increasing the likelihood that the latter is a lineal ancestor of modern squirrel monkeys. PMID- 1900938 TI - Protein kinase C mediates x-ray inducibility of nuclear signal transducers EGR1 and JUN. AB - The cellular response to ionizing radiation includes growth arrest and DNA repair followed by proliferation. Induction of immediate early response genes may participate in signal transduction preceding these phenotypic responses. We analyzed mRNA expression for different classes of immediate early genes (JUN, EGR1, and FOS) after cellular x-irradiation. Increased expression of the EGR1 and JUN genes was observed within 0.5-3 hr following x-ray exposure. Preincubation with cycloheximide was associated with superinduction of JUN and EGR1 in x irradiated cells. Inhibition of protein kinase C activity by prolonged stimulation with phorbol 12-myristate 13-acetate or the protein kinase inhibitor H7 prior to irradiation attenuated the increase in EGR1 and JUN transcripts. FOS expression was not coregulated with that of EGR1 following x-irradiation, suggesting a distinct regulatory pathway of this gene as compared with its regulation following serum and phorbol ester. These data implicate the EGR1 and JUN proteins as signal transducers during the cellular response to radiation injury and suggest that this effect is mediated in part by a protein kinase C dependent pathway. PMID- 1900939 TI - The transcriptional regulator LevR of Bacillus subtilis has domains homologous to both sigma 54- and phosphotransferase system-dependent regulators. AB - The regulatory gene levR of the levanase operon of Bacillus subtilis was cloned and sequenced. It encodes a polypeptide of Mr 106,064 with two domains homologous to members of two families of bacterial activators. One domain in LevR is homologous with one region of bacterial regulators including SacT and SacY of B. subtilis and BglG from Escherichia coli. Another domain of LevR is homologous to one part of the central domain of NifA and NtrC, which control nitrogen assimilation in Gram-negative bacteria. The levanase promoter contains two regions almost identical to the -12, -24 consensus regions present in sigma 54 dependent promoters. The expression of the levanase operon in E. coli was strongly dependent on sigma 54. Taken together, these results suggest that the operon is expressed from a -12, -24 promoter regulated by a sigma 54-like dependent system in B. subtilis. PMID- 1900940 TI - The pituitary gland is required for protection against lethal effects of Salmonella typhimurium. AB - One-half of pituitary-intact or sham-operated rats survive infection with 10(9) colony-forming units of Salmonella typhimurium, whereas rats without a pituitary gland all die within a few days. When the dose of S. typhimurium is reduced 600 fold, 15-25% of the hypophysectomized rats survive, and the survival rate is significantly enhanced by administration of tetracycline, recombinant interferon gamma (IFN-gamma), or recombinant growth hormone (GH). The protective effect of GH is abolished by heat inactivation or with an antibody to GH. Spleens from normal and hypophysectomized rats treated with tetracycline, IFN-gamma, or GH have 59-99% fewer bacteria 5 days after infection as compared to control rats. Peritoneal macrophages from hypophysectomized rats that are infected in vitro with S. typhimurium kill half as many extracellular bacteria as compared to pituitary-intact rats, and this bactericidal capacity is significantly augmented 75-95% by either GH or IFN-gamma. These data establish that the pituitary gland is essential for homeostasis during an infectious episode and that GH plays an important role in host resistance by augmenting the ability of macrophages to kill S. typhimurium. PMID- 1900941 TI - Invariant chain promotes egress of poorly expressed, haplotype-mismatched class II major histocompatibility complex A alpha A beta dimers from the endoplasmic reticulum/cis-Golgi compartment. AB - Invariant chain (Ii) is a nonpolymorphic, non-major histocompatibility complex (MHC)-encoded glycoprotein that rapidly associates with newly synthesized class II MHC alpha and beta chains in the rough endoplasmic reticulum. This oligomerization of Ii, alpha, and beta and their cotransport within the cell led to speculation that Ii was an essential alpha beta transport protein. However, direct tests failed to show an absolute requirement for Ii in class II MHC molecule transport. More recently, it has become clear that different class II alpha beta chain combinations vary greatly in their efficiency of cell-surface expression, based largely on the allelic origin of the alpha and beta amino terminal regions. Because the previous tests of Ii for a role in class II molecule expression utilized efficiently expressed alpha beta combinations, we have reexamined this question with several haplotype-mismatched murine A alpha and A beta chain combinations of various potentials for cell-surface expression. Using a transient expression assay in Ii-negative COS cells, we find that many inefficiently expressed alpha beta combinations show marked augmentation of surface expression upon cosynthesis of Ii. This effect is absent or minimal with evolutionarily coselected, haplotype-matched chains that give efficient expression alone. Biochemical studies show that at least one component of the Ii effect is an increased egress of already formed alpha beta dimers from the rough endoplasmic reticulum/cis-Golgi. We suggest that these results reflect the interaction of Ii with the peptide-binding domain of the poorly expressed class II molecules, either aiding in maintenance of a transportable conformation or competing with endoplasmic reticulum retention proteins, and thus enhancing movement to the cell surface. These results suggest a complex and variable role for trans-associated alpha and beta chains in the immune responses of MHC heterozygotes and provide a method for examining Ii interaction with class II MHC molecules independent of measurement of peptide presentation to T cells. PMID- 1900944 TI - Reduction of the Bremsstrahlung component of clinical electron beams: implications for electron arc therapy and total skin electron irradiation. AB - The dose due to Bremsstrahlung in stationary electron beams of nominal energies in the range 6-20 MeV is typically between 1-7% of the maximum dose and is usually not clinically significant. However, in treatments using rotational or multiple electron beams where the x-ray dose from several beams is added the x ray dose will reach much higher proportions and will be of clinical significance. Moreover, this dose often is located in normal tissue beyond the target volume. Reduction of this x-ray dose is therefore desirable. In the present study a reduction of the x-ray component of electron beams produced by a Clinac 2100C accelerator by a change of the transmission ion chamber and scattering foils is reported. A reduction in Bremsstrahlung of up to 50% can be achieved. PMID- 1900943 TI - Aspirin inhibits interleukin 1-induced prostaglandin H synthase expression in cultured endothelial cells. AB - Prostaglandin H (PGH) synthase (EC 1.14.99.1) is a key enzyme in the biosynthesis of prostaglandins, thromboxane, and prostacyclin. In cultured human umbilical vein endothelial cells, interleukin 1 (IL-1) is known to induce the synthesis of this enzyme, thereby raising the level of PGH synthase protein severalfold over the basal level. Pretreatment with aspirin at low concentrations (0.1-1 micrograms/ml) inhibited more than 60% of the enzyme mass and also the cyclooxygenase activity in IL-1-induced cells with only minimal effects on the basal level of the synthase enzyme in cells without IL-1. Sodium salicylate exhibited a similar inhibitory action whereas indomethacin had no apparent effect. Similarly low levels of aspirin inhibited the increased L-[35S]methionine incorporation into PGH synthase that was induced by IL-1 and also suppressed expression of the 2.7-kilobase PGH synthase mRNA. These results suggest that in cultured endothelial cells a potent inhibition of eicosanoid biosynthetic capacity can be effected by aspirin or salicylate at the level of PGH synthase gene expression. The aspirin effect may well be due to degradation of salicylate. PMID- 1900942 TI - Norepinephrine and isoproterenol increase the phosphorylation of synapsin I and synapsin II in dentate slices of young but not aged Fisher 344 rats. AB - A number of recent reports have suggested that norepinephrine (NE) produces a form of synaptic enhancement that resembles long-term potentiation (LTP). LTP, thought to be an electrophysiological correlate of memory, in part involves an augmentation of transmitter release. Although the effects of NE have not been unequivocally linked to LTP, it is clear that NE can produce increased transmitter release in the dentate gyrus of the hippocampus. The purpose of this study was to determine whether NE was capable of enhancing the phosphorylation of synapsin I and synapsin II, two homologous phosphoproteins thought to be involved in modulation of neurotransmitter release. NE (10 microM) and isoproterenol (250 nM) produced an increase in the phosphorylation of synapsin I and synapsin II in dentate slices from young rats. Phosphorylation site analysis of synapsin I, performed by limited proteolysis, indicated that NE and isoproterenol increased the phosphorylation of synapsin I at sites modified by Ca2+/calmodulin-dependent protein kinase II as well as cAMP-dependent protein kinase. These data demonstrate that NE stimulates the phosphorylation of synapsin I at its Ca2+/calmodulin-dependent protein kinase II site, which is a site that has been shown to regulate the effect of synapsin I on neurotransmitter release. We have also examined the effects of NE and isoproterenol on synapsin phosphorylation in dentate slices prepared from aged animals. Such animals have previously been shown to exhibit deficits in NE sensitivity as well as significant impairment in their ability to exhibit LTP. Neither NE nor isoproterenol stimulated synapsin phosphorylation in slices prepared from aged animals. Interestingly, the basal level of phosphorylation of the synapsin proteins was higher in slices prepared from aged animals. This higher basal level of phosphorylation may underlie the failure of aged animals to exhibit NE-stimulated increases in phosphorylation of the synapsin proteins. We hypothesize that the beta-adrenergic agonist-stimulated phosphorylation of synapsin I and synapsin II in young rats plays a role in the increase in transmitter release produced by NE in the dentate. Thus, the failure of the aged rats to show such phosphorylation may underlie, in part, their failure to exhibit normal responsiveness to NE. Moreover, these deficits in synapsin phosphorylation may also play some role in the deficits in plasticity seen in aged rats. PMID- 1900946 TI - [Alzheimer's disease and amyloid protein precursor gene]. PMID- 1900945 TI - Striatal A2 receptor regulates apomorphine-induced turning in rats with unilateral dopamine denervation. AB - The effect of the purine agonist N-ethylcarboxamido-adenosine (NECA) on apomorphine-induced rotation was investigated in rats with unilateral 6 hydroxydopamine lesions of the nigrostriatal pathway. Intrastriatal administration of NECA on the denervated side caused a dose-dependent inhibition of contralateral rotation. This inhibition was prevented by prior intrastriatal injection of theophylline. The adenosine A1 receptor antagonist 8 cyclopentyltheophylline was ineffective at concentrations which block this receptor, but effective in preventing the action of NECA at concentrations which block the adenosine A2 receptor. In the absence of apomorphine, NECA had no effect on behaviour. It is concluded that A2 receptor activation counteracts apomorphine effects in the striatum. Since the A2 receptor may be localized to striatal cholinergic neurones, the possible role of these neurones in purine induced behaviours is discussed. PMID- 1900947 TI - [Abnormal proteins in the brain in Alzheimer's disease]. PMID- 1900948 TI - Cost-effectiveness of alternative medications in the treatment of duodenal ulcer. AB - This study examines the differential costs of various medications in the treatment of duodenal ulcer. Two approaches are taken. The first estimates the (differential) cost per year of life before relapse can be expected to occur, for five different medications. The second approach estimates the cost of treating a duodenal ulcer over a 5-year period during which ranitidine, cimetidine, or colloidal bismuth subcitrate (CBS) is used in the initial course of treatment. Expected rates of relapse and the probability of receiving maintenance therapy are taken into account. The results of both approaches suggest that CBS costs considerably less than other medications to achieve a similar outcome. It is concluded that, as well as the clinical benefits associated with slower relapse, the potential economic benefits of CBS are substantial. PMID- 1900949 TI - Verdict in sight in the "Baltimore case". PMID- 1900950 TI - Induction of self-tolerance in T cells but not B cells of transgenic mice expressing little self antigen. AB - Self-tolerance to a transgene-encoded protein, hen egg lysozyme, was examined in the T and B cell repertoires of a series of lines of transgenic mice that expressed different serum concentrations of soluble lysozyme. T cells were tolerant in all lines in which lysozyme was expressed irrespective of the antigen concentration, whereas B cell tolerance did not occur when the serum lysozyme concentration was less than 1.5 nanograms per milliliter (0.1 nM). Induction of elevated transgene expression could restore B cell tolerance. These findings support the hypothesis that autoimmune disease may in some instances arise through a bypass of T cell tolerance. PMID- 1900951 TI - Peripheral selection of the T cell repertoire. AB - T lymphocytes undergo selection events not only in the thymus, but also after they leave the thymus and reside in the periphery. Peripheral selection was found to be dependent on T cell receptor (TCR)-ligand interactions but to differ from thymic selection with regard to specificity and mechanism. Unlike thymic selection, peripheral selection required binding of antigen to the TCR, and it induced expansion of T cell clones. Tolerance to self antigens that are restricted to the periphery occurred through the elimination of self-reactive T cells and by the clonal anergy, which was associated with down-regulation of the alpha beta TCR and CD8. PMID- 1900952 TI - Split anergy in a CD8+ T cell: receptor-dependent cytolysis in the absence of interleukin-2 production. AB - Engagement of the antigen-specific receptor (TCR) of CD4+ T lymphocytes without a second (costimulatory) signal prevents the subsequent production of interleukin-2 (IL-2) by these cells. Because IL-2 is a key immunoregulatory lymphokine and is also produced by a subset of CD8+ T cells that are able to kill target cells, the effect of engaging the TCR of one such clone in the absence of costimulatory signals was examined. The capacity for TCR-dependent IL-2 production was lost, indicating comparable costimulator-dependent signaling requirements for IL-2 production in CD4+ and CD8+ T cells. However, TCR-mediated cytotoxicity was not impaired, implying that costimulation is required for only certain TCR-dependent effector functions. PMID- 1900953 TI - A nonconservative serine to cysteine mutation in the sulfate-binding protein, a transport receptor. AB - Serine 130 is one of seven residues that form a total of seven hydrogen bonds with the sulfate completely sequestered deep in the cleft between the two lobes of the bilobate sulfate-binding protein from Salmonella typhimurium. This residue has been replaced with Cys, Ala, and Gly by site-directed mutagenesis in an Escherichia coli expression system. Replacement with the isosteric Cys caused a 3200-fold decrease in the sulfate-binding activity relative to the wild-type activity, whereas replacement with Ala and Gly resulted in only 100- and 15-fold decreases, respectively. The effect of the Cys substitution is attributed largely to steric effect, whereas the Gly substitution more nearly reflects the loss of one hydrogen bond to the bound sulfate with a strength of only 1.6 kilocalories per mole. PMID- 1900954 TI - Cross-regulatory interactions between the proneural achaete and scute genes of Drosophila. AB - The achaete (ac) and scute (sc) genes of Drosophila allow cells to become sensory organ mother cells. Although ac and sc have similar patterns of expression, deletion of either gene removes specific subsets of sensory organs. This specificity was shown to reside in the peculiar regulation of ac and sc expression. These genes are first activated in complementary spatial domains in response to different cis-regulatory sequences. Each gene product then stimulates expression of the other gene, thus generating similar patterns of expression. Therefore, removal of one gene leads to the absence of both proneural gene products and sensory organs in the sites specified by its cis-regulatory sequences. PMID- 1900955 TI - The development of community mental health centres in the U.K. AB - This paper describes a survey of British Community Mental Health Centres (CMHCs). CMHCs are by far the most visible manifestation of the implementation of community mental health care policies of the 1980s. While these centres have demonstrated achievements in terms of accessibility, co-ordination and responsiveness to clients, they have also been bedevilled by ambiguity. The vast majority of CMHCs aim to serve the needs of all forms of mental illness within their catchment area, yet in practice, they have frequently failed to meet the needs of people with long term severe disorders and concentrate instead on providing assessment and counseling services for neurotic and transient situational disorders. It appears that this is a function of an early failure of multidisciplinary teams to delineate boundaries and priorities. If the British CMHC movement sharpens its focus and combines this with a determination to address the complexities involved in both rationing and enhancing choice, it could begin to improve upon rather than simply repeat the history of similar developments in America. PMID- 1900956 TI - Long-term utilization of community mental health outpatient services in Jerusalem. AB - A survey of the long-term users of community mental health clinics in Jerusalem was conducted in 1986. The study population included all patients in regular contact for at least one year (789 patients). Data on clinical diagnosis, type of treatment and selected sociodemographic variables were extracted from the patient's file at the clinic. Long-term utilization rates were calculated for the different catchment areas and for different sociodemographic and diagnostic groups. It was found that for patients suffering from major psychiatric disorders (2/3 of the long-term users), the long-term utilization rates were similar across catchment areas, and higher in those socioeconomic groups that are also reported to have high true prevalence rates. On the other hand, for patients suffering from non major psychiatric disorders, the long-term utilization rates varied between clinics, reflecting local treatment policies, specifically the extent to which the clinics use psychotherapy as a treatment modality. PMID- 1900957 TI - Splenectomy attenuates the inappropriate diuresis associated with tumor necrosis factor administration. AB - Tumor necrosis factor (TNF) is an important mediator of the systemic response to gram-negative sepsis and endotoxemia. We studied the renal effects of a sublethal TNF infusion in dogs (0.54 = 10(5) international units per kilogram of body weight during a six hour period). The TNF-infused dogs (n = 4) had marked polyuria and natriuresis in comparison with those in the control group (n = 12) (urine output, 35.3 +/- 4.1 versus 3.7 +/- 0.5 millimeters per kilogram per six hours p less than 0.01; sodium excretion, 2.82 +/- 0.27 versus 0.75 +/- 0.19, p less than 0.01). To evaluate the role of the spleen in this response, seven dogs that had splenectomy were infused with TNF. Splenectomy abolished both the polyuria and the natriuresis; this could not be explained by the differences in fluid balance or in hemodynamic or metabolic alterations. Treatment with ibuprofen given intravenously (12.5 milligrams per kilogram 40 minutes before and three hours after the beginning of TNF infusion) in eight dogs that did not undergo splenectomy also abolished these renal effects. Prostaglandin 2 (PGE2) concentrations in selected blood samples from the splenic vein did not increase with TNF infusion, excluding circulating PGE2 as a possible mediator of the renal effects. The results of these studies indicate that, during septic challenge or severe inflammation, the spleen participates in signaling the kidney to increase water and sodium excretion. These renal events are mediated through the cyclo oxygenase pathway. PMID- 1900958 TI - [Hospital financing based on itemized pricing--is it a good idea?]. PMID- 1900959 TI - Physiologically based pharmacokinetic modeling with dichloromethane, its metabolite, carbon monoxide, and blood carboxyhemoglobin in rats and humans. AB - Dichloromethane (methylene chloride, DCM) and other dihalomethanes are metabolized to carbon monoxide (CO) which reversibly binds hemoglobin and is eliminated by exhalation. We have developed a physiologically based pharmacokinetic (PB-PK) model which describes the kinetics of CO, carboxyhemoglobin (HbCO), and parent dihalomethane, and have applied this model to examine the inhalation kinetics of CO and of DCM in rats and humans. The portion of the model describing CO and HbCO kinetics was adapted from the Coburn Forster-Kane equation, after modification to include production of CO by DCM oxidation. DCM kinetics and metabolism were described by a generic PB-PK model for volatile chemicals (RAMSEY AND ANDERSEN, Toxicol. Appl. Pharmacol. 73, 159 175, 1984). Physiological and biochemical constants for CO were first estimated by exposing rats to 200 ppm CO for 2 hr and examining the time course of HbCO after cessation of CO exposure. These CO inhalation studies provided estimates of CO diffusing capacity under free breathing and for the Haldane coefficient, the relative equilibrium distribution ratio for hemoglobin between CO and O2. The CO model was then coupled to a PB-PK model for DCM to predict HbCO time course behavior during and after DCM exposures in rats. By coupling the models it was possible to estimate the yield of CO from oxidation of DCM. In rats only about 0.7 mol of CO are produced from 1 mol of DCM during oxidation. The combined model adequately represented HbCO and DCM behavior following 4-hr exposures to 200 or 1000 ppm DCM, and HbCO behavior following 1/2-hr exposure to 5160 ppm DCM or 5000 ppm bromochloromethane. The rat PB-PK model was scaled to predict DCM, HbCO, and CO kinetics in humans exposed either to DCM or to CO. Three human data sets from the literature were examined: (1) inhalation of CO at 50, 100, 250, and 500 ppm; (2) seven 1/2-hr inhalation exposures to 50, 100, 250, and 500 ppm DCM; and (3) 2 hr inhalation exposures to 986 ppm DCM. An additional data set from human volunteers exposed to 100 or 350 ppm DCM for 6 hr is reported here for the first time. Endogenous CO production rates and the initial amount of CO in the blood compartment were varied in each study as necessary to give the baseline HbCO value, which varied from less than 0.5% to greater than 2% HbCO. The combined PB PK model gave a good representation of the observed behavior in all four human studies.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1900960 TI - Differential induction of cytochromes P450 and cytochrome P450-dependent arachidonic acid metabolism by 3,4,5,3',4'-pentachlorobiphenyl in the rat and the guinea pig. AB - Differential induction of hepatic cytochromes P450 by 3,4,5,3',4' pentachlorobiphenyl (PENCB) has been observed in the rat and the guinea pig: (1) in rat and guinea pig, treatment with the chosen dose levels resulted in significant induction of total, carbon monoxide-discernible cytochrome P450 content; the absorption maximum of the CO-adduct of the dithionite-reduced microsomes from PENCB-induced rat liver was shifted from 450 to 448 nm, whereas its counterpart in the guinea pig did not; (2) PENCB treatment significantly increased EROD activity in rat liver microsomes (up to 60-fold), but the increase in the guinea pig was less than fivefold; (3) PENCB-induced rat liver microsomes significantly induced the omega-1 hydroxylation of arachidonic acid (AA); however, omega-1 hydroxylation of AA was hardly affected by PENCB treatment in the guinea pig. Instead, omega-hydroxylation was significantly increased in this latter species. In addition to omega-1 hydroxylation in the rat or omega hydroxylation in the guinea pig, an additional AA metabolite (designated peak III) was significantly induced by PENCB in both rat and guinea pig; (4) Western blot and ELISA analyses with polyclonal anti-P450 IA1/IA2 and IVA1 antibodies demonstrated that P450 IA1 was significantly induced in the rat but only slightly induced in the guinea pig, whereas P450 IVA1 was significantly suppressed in the rat but significantly induced in the guinea pig by PENCB treatment. The induction of the third arachidonic acid metabolite peak, Peak III, in both rat and guinea pig, particularly in the guinea pig, is obviously neither mediated by P450 IA1 nor by P450 IV A1. At present, it is still unclear which form(s) of cytochrome P450 isoenzymes is responsible for this latter hydroxylation of arachidonic acid. PMID- 1900961 TI - Significance of biochemical markers in early detection of canine lung allograft rejection. AB - To evaluate the significance of bronchoalveolar lavage fluid, levels of tumor necrosis factor-alpha (TNF), gamma-interferon, interleukin 2, and soluble IL-2 receptor in early detection of canine lung allograft rejection, bronchoalveolar lavages were performed serially in mongrel dogs before and after single lung transplantation. The dogs were divided into three groups. Group 1 (control group) consisted of one in which neither donor nor recipient dogs were treated with cyclosporine. In group 2 (CsA-pretreated group) only donors were treated with CsA orally at a single dose of 20 mg/kg/day for 3 days prior to single lung transplantation. In group 3 only recipients were treated with CsA orally at a single dose of 20 mg/kg/day for a short period of 9 days after single-lung transplantation. Marked elevation was found of TNF, IFN-gamma, IL-2, and IL-2R in BALF obtained from the grafted lungs in group 1 and group 2 dogs. The levels of these markers were significantly higher than those obtained from the normal, native lungs (P less than 0.05). Two of three recipients in group 2 had pneumonia in the native lungs on day 10 after single-lung transplantation. All markers except IFN-gamma in BALF obtained from the infected native lungs were also increased, but the titers were less than those obtained from the grafted lungs at the same time. There were significantly higher levels of TNF, IL-2, and IL-2R present in the BALF of grafted lungs of dogs in group 1 than group 2 (P less than 0.05). In group 3, BALF levels of these markers from the grafted lungs were not significantly different from those of the normal and native lungs during the period of CsA treatment after single-lung transplantation. On various days after discontinuation of CsA treatment, BALF levels of all markers began to rise. Abnormal levels of BALF markers obtained from the grafted lungs heralded the appearance of abnormalities detected by chest x-ray films. Our study suggests that serially measuring BALF levels of TNF, IFN-gamma, IL-2, and IL-2R may serve as a useful means in monitoring the immunologic status of canine lung allografts and in the early detection of lung allograft rejection. The role of BALF IFN gamma in distinguishing lung allograft rejection from pulmonary infection needs further studies. PMID- 1900962 TI - Differential in situ expression of cytokines in renal allograft rejection. AB - The expression of the interleukin 6, tumor necrosis factor alpha, and interferon gamma (IFN-gamma) genes was studied in human renal biopsies from individuals without evidence of kidney disease and from patients undergoing acute renal allograft rejection using a method of in situ hybridization capable of detecting 1-5 copies of a specific cellular messenger RNA in individual cells. IL-6, TNF alpha, and IFN-gamma RNA transcripts were not detected in any of the sections of normal human kidneys. Elevated levels of IL-6 mRNA but not IFN-gamma were, however, detected in the sections of the renal biopsies from six of eight patients exhibiting acute rejection. A uniform level of expression of IL-6 mRNA was observed in all the cells examined, including glomerular cells, tubular epithelia, smooth muscle cells, and vascular endothelia, as well as the interstitial mononuclear infiltrate. Juxtatabular clusters of TNF-alpha mRNA were detected in the absence of IL-6 mRNA in one patient exhibiting acute rejection. Only a small number of grains (1-5 per high-power field) was detected in the urinary space or in the tubular or vascular lumen following hybridization with the IL-6 or TNF-alpha probes. In contrast, in kidney transplant patients with stable renal function no significant labeling was observed with the IL-6, TNF alpha, or IFN-gamma probes. A similar level of expression of actin mRNA was observed in all the sections of normal and transplanted kidneys studied, suggesting that the overall level of RNA synthesis was similar in both groups. These results suggest that cytokines such as IL-6 play a role in acute allograft rejection. PMID- 1900963 TI - Utility of pulsed Doppler in the diagnosis and follow-up of acute vascular graft rejection treated with OKT3 monoclonal antibody or antilymphocyte serum. AB - Fifteen patients with severe acute vascular graft rejection (twelve of them steroid-resistant) treated with OKT3 monoclonal antibody (8) or antilymphocyte serum (7) were sequentially studied with duplex-Doppler ultrasonography (DDUS). Measurements of intrarenal resistance were obtained by means of the resistive index (RI). During rejection episodes, the intrarenal resistance was increased in all patients (RI range: 0.89-1), with absent or reversed diastolic blood flow. Normalization of diastolic blood flow was documented prior to the decrease of serum creatinine level in all patients who recovered from a rejection episode. We conclude that DDUS is a noninvasive technique useful in the diagnosis and monitoring of acute vascular graft rejection. Prediction of graft outcome after rejection treatment could probably be made based on DDUS findings. PMID- 1900964 TI - Three-dimensional ultrastructure of glomerular injury in serum sickness nephritis using the quick-freezing and deep-etching method. AB - The three-dimensional ultrastructure of the glomerulus in serum sickness nephritis has been investigated by the quick-freezing and deep-etching method. Compact granular immune deposits were localized in filamentous networks in the lamina densa and mesangial matrices. These constitutional fibrils with diameters of 8-15 nm, were directly attached to the immune deposits. The filamentous networks became markedly loosened around the deposits. In podocytes, reticular microfilaments with positive decoration by myosin subfragment 1 (S1) were increased in flattened foot processes and directly attached to the cell membranes. Fine filaments with diameters of 4-7 nm were undecorated by S1 and connected with actin filaments as cross-bridges. Intermediate filaments were also increased in the cell bodies and primary processes of podocytes. Connecting fibrils in lamina rara externa were partially disrupted. The immune deposits were primarily detected in the networks of lamina densa and actually destroyed the size barrier composed of filamentous networks. Moreover, the mesangial deposits also disorganized mesangial networks to probably alter mesangial flow through the matrices. Increased actin filaments in foot processes seemingly reinforced the cell membranes and the connecting fibrils in lamina rara externa, which prevented the initial detachment of podocytes from the basement membrane. PMID- 1900965 TI - Growth characteristics and metastatic potential of seven intestinal carcinoma lines serially passaged in syngeneic rats. AB - Transplantable tumour lines were obtained from one duodenal carcinoma induced by N-methyl-N'-nitro-N-nitrosoguanidine in the Lewis rat and from six colonic carcinomas induced by 1,2 dimethylhydrazine in BDIX or Fisher rats. The tumours were serially transplanted by the subcutaneous route into homologous syngeneic rats. The seven tumours differ from one another in their histological structure, five of them being well or moderately differentiated adenocarcinomas, and in their capacity to produce neutral or acidic mucins. The seven tumours also differ in their growth rate. The seven lines produced metastases; the metastatic potential and the location of the metastases differed from one line to another. The seven lines kept their original differentiation characteristics through multiple passages, representing several years of transplantation into syngeneic hosts. These tumours represent a useful and diversified model of metastatic intestinal carcinoma, available for basic research and therapeutic trials. PMID- 1900966 TI - "Desmoplastic" versus "classic" medulloblastoma: comparison of DNA content, histopathology and differentiation. AB - A microfluorometric analysis was performed to analyse the DNA content of 42 medulloblastomas (MBs) and to seek correlations, if any existed, between the DNA distribution and ploidy values, neoplasm types (i.e. classic vs desmoplastic), histological features of aggressiveness, and immunocytochemical features indicating glial and/or neuronal differentiation. Thirty-one cases were classified as classic and 11 cases as desmoplastic MBs. Ten of 11 desmoplastic MBs had a near-diploid main mode and the remaining 1 case had a near-tetraploid main mode. Moreover, 10 of 11 (90%) cases showed a "monomodal" DNA distribution diagram. All these cases showed a uniform histology. In contrast, classic MBs represented a heterogeneous group of neoplasms. Twenty-two cases were near diploid, 5 cases were near-tetraploid and 3 cases were near-triploid. The histogram type distribution showed a similar heterogeneity. Twelve of 31 (39%) cases had a monomodal histogram, 12 (39%) cases had a bimodal diagram and 7 (22%) cases a complex DNA distribution. There was a statistically significant difference (P less than 0.001) in terms of prevalence of DNA monomodal histograms between classic and desmoplastic MBs. Significant correlations were not observed among classic MBs between histological features of aggressiveness, type and degree of differentiation and DNA distribution. The present study indicates that desmoplastic MBs represent a homogeneous group of neoplasms in terms of histology and DNA distribution. In contrast, classic MBs are lesions with different degrees of histologically apparent aggressiveness and a complex DNA distribution. PMID- 1900967 TI - Necrotizing lymphadenitis: a clinicopathological and immunohistochemical study of four familial cases and five recurrent cases. AB - We report the clinicopathological and immunohistological findings of nine cases of necrotizing lymphadenitis, consisting of four cases of familial infection and five cases of recurrence. Fever, cervical lymphadenopathy, leucopenia and swelling of the tonsils are characteristic clinical findings. Morphological features of the lymph nodes include the presence of immunoblasts, plasmacytoid T cells, histiocytes and macrophages, the latter with phagocytized nuclear debris derived from degenerated lymphocytes. However, granulocytes are generally absent. Ultrastructurally, tubuloreticular structures are observed not only in lymphoid cells, but in vascular endothelial cells. Immunological studies of peripheral blood using monoclonal antibodies disclose that CD 8+ (Leu 2a+; suppressor/cytotoxic) cells predominate at the onset, but they gradually decrease with the clinical course and the ratio of CD 4+: CD 8+ (helper:suppressor) increases as the disease progresses. However, in the affected lymph nodes, CD4+ (Leu 2a+: helper/inducer) cells often increase with the clinical progression, but the ratio of CD 4+:CD 8+ in the lymph nodes does not correlate with clinical progression. In addition, Ki-67+CD 8+ cells are more often seen than Ki-67+CD 4+ cells. It is suggested that necrotizing lymphadenitis is an infectious disease in which CD 4+ cells are disrupted and CD 8+ cells undergo transformation to blastoid cells. This results in a change in the ratio of T subsets. PMID- 1900968 TI - Stereological estimates of nuclear volume in squamous cell carcinoma of the uterine cervix and its precursors. AB - Using modern stereology, this study was carried out to obtain base-line data concerning three-dimensional, mean nuclear size in precancerous and invasive lesions of the uterine cervix. Unbiased estimates of the volume-weighted mean nuclear volume (nuclear vv) were obtained by point-sampling of nuclear intercepts in 51 pre-treatment biopsies from patients with invasive squamous cell carcinomas (SCC). Vertical sections from 27 specimens with cervical intraepithelial neoplasia (CIN) grades I through III were also investigated, along with 10 CIN III associated with microinvasion (CIN III + M). On average, nuclear vv was larger in SCC than in CIN III and CIN III + M together (2 P = 8.9 . 10(-5). A conspicuous overlap of nuclear vv existed between all investigated lesional groups. The reproducibility of estimates of nuclear vv in biopsies with SCC was acceptable (r = 0.85 and r = 0.84 in intra- and inter-observer studies, respectively). The efficiency of the sampling scheme was high, with more than 60% and more than 80% of the total observed variance contributed by differences between individual lesions with CIN and SCC, respectively. Estimates of nuclear vv based on sampling within the whole epithelial thickness and on sampling in the lower one-third in CIN I and the lower two-thirds in CIN II lesions were of the same magnitude. Approximate estimates of the absolute variation of nuclear vv were directly proportional to individual estimates of nuclear vv, whereas the relative variation of nuclear vv tended to decrease with increasing mean nuclear volume. Based on the rather small number of cases investigated, estimates of nuclear vv are unable to distinguish between different grades of CIN. However, the estimation of nuclear vv is well-suited for the purposes of objective grading of malignancy in SCC. PMID- 1900969 TI - Sinonasal non-Hodgkin's lymphomas and Wegener's granulomatosis: a clinicopathological study. AB - Reports of sinonasal non-Hodgkin's lymphomas, analysed with monoclonal antibodies, are scarce, and differentiation of these lymphomas from Wegener's granulomatosis can be difficult. In this study, we investigated histopathologically and immunohistologically 20 cases of non-Hodgkin's lymphoma, primary in the sinonasal region, and sinonasal biopsies from 11 patients with Wegener's granulomatosis. All T-cell lymphomas (n = 7) and plasmacytomas (n = 4) were stage I at clinical presentation, while all B-cell lymphomas (n = 9) presented at higher stages. T-cell lymphomas tended to be more frequent in the nasal cavity and paranasal sinuses; B-cell lymphomas more often presented in the nasopharynx. Remarkably, 1 B-cell lymphoma expressed MT1, and 1 T-cell lymphoma expressed L26 (CD 20). The follow-up of 2 patients with a clinical diagnosis of Wegener's granulomatosis was suggestive of non-Hodgkin's lymphoma. Retrospective immunohistochemical analysis revealed that the original histological diagnosis of non-specific inflammation had to be changed to T-cell lymphoma, pleomorphic small cell type. We conclude that a biopsy from the sinonasal region with a dense inflammatory infiltrate, consisting predominantly of T-lymphocytes, renders a diagnosis of Wegener's granulomatosis unlikely and is at least suspicious of T cell lymphoma. Immunohistochemical analysis is warranted for this type of biopsy. PMID- 1900970 TI - Absence of macrophage and presence of plasmacellular iron storage in the terminal duodenum of patients with hereditary haemochromatosis. AB - Biopsy specimens of the terminal duodenum obtained from 11 patients with hereditary haemochromatosis were examined by light and electron microscopy. Stainable iron was found in the lamina propria of the terminal duodenum in only 4 patients, all of whom were in an advanced stage of the disease. The iron was localized in the basal parts of the villi, sparing their tips, and between the crypts of Lieberkuhn. The iron-storing cells could be identified as plasma cells, in which ferritin and haemosiderin were localized within lysosomes and ferritin molecules scattered in the cell sap. There was no storage of iron in macrophages. These observations demonstrate the impaired iron-storing capacity of macrophages in hereditary haemochromatosis, which may be related to the increased iron absorption in this iron storage disease. PMID- 1900972 TI - Claws of cilia: further observation of ciliated epithelium in neurenteric cyst. AB - Claw-like projections and related structures on cilium tips in neurenteric cyst epithelium are described. The ciliary claws are about 20 nm in length and just beneath them four parallel electron-dense areas or lines are discernible. Similar structures were also observed in another case of neurenteric cyst. These structures are very similar to those reported previously, and it is suggested that they are commonly present in various ciliated epithelia in Man. PMID- 1900971 TI - Histochemistry of tartrate-resistant acid phosphatase and carbonic anhydrase isoenzyme II in osteoclast-like giant cells in bone tumours. AB - Using routinely processed, paraffin-embedded tissue specimens, osteoclast-like giant cells in giant cell tumour of bone (GCT), chondroblastoma, osteoblastoma and osteoblastic osteosarcoma were examined histochemically for osteoclast specific enzymes tartrate-resistant acid phosphatase (TRAP) and carbonic anhydrase isoenzyme II (CA-II). Osteoclast-like giant cells and some mononuclear cells possessed TRAP activity. These were further classified with respect to CA II immunoreactivity, i.e. cells with CA-II were seen in GCT and chondroblastoma, while those in osteoblastoma and osteoblastic osteosarcoma were negative for CA II. All the cellular components in malignant fibrous histiocytoma and various extraosseous inflammatory lesions including malignant giant cells and macrophage polykaryons were negative for both TRAP and CA-II. These results indicate that osteoclast-like giant cells in GCT, chondroblastoma, osteoblastoma and osteoblastic osteosarcoma are all osteoclasts and generated by fusion of mononuclear cells with the same histochemical characteristics as osteoclast-like giant cells. The difference in CA-II immunoreactivity suggests the functional or maturational difference between osteoclast-like giant cells in GCT and chondroblastoma and those in osteoblastoma and osteosarcoma. PMID- 1900973 TI - Angiocentric immunoproliferative lesion of the stomach. AB - We report here a rare case of angiocentric immunoproliferative lesion (AIL) of the stomach. The patient was a 61-year-old Japanese female whose medical history was unremarkable. Following a complaint of abdominal discomfort, a submucosal tumour of the stomach was found and gastrectomy was done. Histological examination of the tumour revealed multiple angiocentric or angiodestructive lesions with numerous lymphocytic infiltrates. These vascular lesions were histologically the same as those in benign lymphocytic vasculitis with granulomatosis (BLV) of the respiratory tract. AIL is a distinct entity, including BLV, lymphomatoid granulomatosis and angiocentric lymphoma with BLV representing a good prognosis group of AIL. A survey of the literature suggests that AIL is a spectrum of T-lymphocyte proliferative disorders. To our knowledge, this is the first case of AIL involving the stomach primarily. PMID- 1900974 TI - Epithelioid sarcoma mimicking angiosarcoma: the value of immunohistochemistry in the differential diagnosis. AB - Epithelioid sarcoma (ES) is a rare malignant tumour of young adults, usually presenting as a skin ulcer or subcutaneous nodule in the distal portion of the upper limb. Multiple recurrences and late metastases are typical, leading to fatality in a third to one-half of all cases. The slow evolution of the tumour is one reason for its delayed recognition. The other is its frequent histological misinterpretation, in particular, as a peculiar granulomatous reaction. In our case, the primary tumour presented a variant morphological pattern so closely mimicking a cavernous angiosarcoma as to mislead several reputable opinions. Later recurrences and metastases were typical of ES, while a focal angiomatoid pattern was maintained. The morphology and immunoreactivity to a wide spectrum of tumour markers is compared with that of six file cases of classical ES. Retrospectively, all neoplastic lesions in our patient were ES. In young adults, lesions of the upper extremity, even when angiomatoid or haemorrhagic, should raise a suspicion of ES. Once epithelioid sarcoma is suspected, the differential diagnosis can be elucidated on immunohistochemical grounds. Early diagnosis provides the best opportunity for radical surgery at a stage when the tumour has not spread locally or disseminated systemically. PMID- 1900975 TI - Cricopharyngeal myotomy with diverticulopexy for Zenker's diverticulum. AB - Prolonged cricopharyngeal dysfunction due to various causes can lead to severe dysphagia, aspiration, pneumonia, debilitation and subsequent pharyngoesophageal (Zenker's) diverticulum. This paper reports the successful use of cricopharyngeal myotomy with diverticulopexy for management of huge Zenker's diverticulum on five high-risk patients. The advantages of this method are immediate swallowing, short hospitalization, and avoidance of serious complication. PMID- 1900976 TI - Tryptophan and eosinophilia-myalgia syndrome. PMID- 1900977 TI - Reduction in the frequency of ventricular late potentials after acute myocardial infarction by early thrombolytic therapy. AB - Ventricular late potentials are strong predictors of arrhythmic events after acute myocardial infarction (AMI). To assess the effect of intravenous thrombolysis on the incidence of ventricular late potentials, 223 consecutive patients surviving a first AMI were included in the present study: 59 patients (53 men, 6 women, mean age +/- standard deviation 55 +/- 10 years) received intravenous recombinant tissue-type plasminogen activator (100 mg over 3 hours, group A) and 164 patients (123 men, 41 women, mean age 61 +/- 11 years) received conventional medical treatment (group B). A time-domain signal-averaged electrocardiogram and a high-resolution beat-to-beat recording (gain 10(6), filters 100 to 300 Hz) were performed at 10 +/- 3 days after AMI. There was no difference between group A and B patients in terms of AMI location (anterior in 28 of 59 vs 80 of 164, difference not significant [NS]), mean left ventricular ejection fraction (55 +/- 10 vs 55 +/- 13%, NS), or presence of heart failure (New York Heart Association class III or IV in 12 of 59 vs 40 of 164, NS). The incidence of ventricular late potentials was 10% (6 of 59) in group A and 24% (39 of 164) in group B (p less than 0.05). Among the 146 patients who underwent coronary arteriography, the incidence of ventricular late potentials was 13% (10 of 80) in patients with a patent infarct-related artery and 26% (17 of 66) in patients with an occluded infarct-related artery (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1900978 TI - Usefulness of flecainide for prevention of paroxysmal atrial fibrillation and flutter. Danish-Norwegian Flecainide Multicenter Study Group. AB - To evaluate the efficacy of flecainide acetate in the prevention of paroxysmal atrial fibrillation and flutter, 43 patients (23 men) (mean age 53 years) were randomized blindly to receive either placebo or 150 mg of flecainide twice per day for consecutive periods of 3 months. Attacks were verified by a minielectrocardiogram event recorder. If intolerable symptoms developed, the protocol allowed patients to cross over between treatments before the end of the first 3-month period. Four patients crossed over prematurely, between 1 week and 1 month, and 15 between 1 month and 3 months. The remaining 24 patients completed both 3-month periods. In all 3 treatment intervals, there was a significant reduction in the number of attacks during flecainide treatment (p less than 0.002). Complete suppression was seen in 15 of 43 patients (35%) treated with flecainide for 1 week, in 18 of 39 (46%) treated for 1 month and in 12 of 24 (50%) completing all 3 months in each period. Adverse effects were reported in 32 of the 43 patients (74%) treated with flecainide, but only 2 were withdrawals. One patient died suddenly. In comparison, 3 of 43 patients (7%) reported adverse effects in the placebo group. In conclusion, flecainide significantly suppressed the number of attacks of paroxysmal atrial fibrillation and flutter. Adverse effects were frequent but were mostly tolerable. PMID- 1900979 TI - Effects of superoxide dismutase on reperfusion arrhythmias and left ventricular function in patients undergoing thrombolysis for anterior wall acute myocardial infarction. PMID- 1900980 TI - Cardiovascular effects of bupropion in depressed patients with heart disease. AB - OBJECTIVE: The cardiovascular effects of therapeutic plasma levels of tricyclic antidepressants in depressed patients with and without preexisting cardiac disease have been well characterized and include orthostatic hypotension and conduction delay. Bupropion, structurally unrelated to tricyclic antidepressants, is relatively free of cardiac side effects in depressed patients without cardiac disease. However, it is unknown whether bupropion is safe for depressed patients with preexisting heart disease, so the authors studied the cardiovascular effects of bupropion in such patients. METHOD: The subjects were 36 inpatients with DSM III major depression and preexisting left ventricular impairment (N = 15), ventricular arrhythmias (N = 15), and/or conduction disease (N = 21). The patients continued their cardiac drug regimens and received bupropion for 3 weeks (mean +/- SD dose = 442 +/- 47 mg/day). Cardiovascular functioning was measured by pulse, blood pressure, high-speed ECG, 24-hour portable ECG, and radionuclide angiography. RESULTS: Although bupropion caused a rise in supine blood pressure, it did not cause significant conduction complications, did not exacerbate ventricular arrhythmias, had a low rate of orthostatic hypotension, and had no effect on pulse rate. However, bupropion treatment was discontinued for 14% of the patients because of adverse effects, including exacerbation of baseline hypertension in two patients. CONCLUSIONS: The cardiovascular profile of bupropion may make this drug a useful agent in the treatment of the depressed patient with preexisting cardiovascular disease. Further studies, with longer durations of bupropion treatment and more subjects, are needed to confirm these findings. PMID- 1900981 TI - Mania in an elderly man treated with bupropion. PMID- 1900982 TI - Sequestration of glyceryl trinitrate (nitroglycerin) by cardiopulmonary bypass oxygenators. AB - The effectiveness of glyceryl trinitrate (nitroglycerin) in controlling myocardial ischemia and blood pressure during coronary artery bypass graft surgery is frequently lost during surgery, possibly as a result of drug sequestration by the cardiopulmonary bypass circuit. The objective of this study was to utilize a gas-liquid chromatographic assay to determine the extent of removal of glyceryl trinitrate from the priming fluid by the bubble and membrane oxygenators. The apparatus was maintained at either 25 or 37 degrees C, the two extreme temperatures experienced by the patient during bypass surgery. At apparent steady state, the circulating glyceryl trinitrate concentration was decreased by 20.6%, 46.6%, and 67.3% with the Maxima membrane oxygenator, Cobe membrane oxygenator, and Bentley bubble oxygenator, respectively. The three-layer defoaming filters that are used in the Bentley bubble oxygenator were studied by immersing each of the three filters in fluid containing 60 nM glyceryl trinitrate and monitoring the drug concentration in Plasmalyte. The filters sequestered approximately 90% of the glyceryl trinitrate from the bathing solution of which 31% was recovered with a single methanol wash of the polyurethane filter. These data demonstrate that the different oxygenators used in the cardiopulmonary bypass circuit remove glyceryl trinitrate to varying degrees from the circulating fluid. PMID- 1900983 TI - Acute ventilatory response to green coffee dust extract. AB - The lung function response to inhalation of an extract of green coffee was studied in ten healthy subjects who were prescreened for airway hyperresponsiveness to an aerosol of green coffee extract. The effects of this provocation were evaluated at rest and following moderate exercise as well as with and without pretreatment with 80 mg of disodium cromoglycate (DSCG). There was a statistically significant decrement in lung function over time (P less than .001) following coffee provocation both at rest and following exercise. No significant protection against this response was observed with DSCG pretreatment. While the majority of these "healthy" coffee reactors exhibited baseline nonspecific airway hyperresponsiveness to methacholine (PC20 FEV1 less than 25 mg/mL in 7/10), there was no correlation in these ten subjects between baseline responsiveness to methacholine and the degree of lung function decrement following coffee (P greater than .05). Also, no correlation was observed between skin prick and lung function response to coffee extract. We conclude that inhalation of green coffee extract causes significant bronchoconstriction in selected healthy volunteers and that this response is not prevented by pretreatment with DSCG. PMID- 1900984 TI - Periodic acid-Schiff-positive organisms in primary cutaneous Bacillus cereus infection. Case report and an investigation of the periodic acid-Schiff staining properties of bacteria. AB - Primary cutaneous Bacillus cereus infection frequently presents as a single necrotic bulla on the extremity of an immunocompromised patient. In lesional biopsy specimens and smears, the large gram-positive rods of B cereus may be mistaken for Clostridium species. This is a potentially serious error, as Bacillus species are resistant to penicillin and other beta-lactam antibiotics. We studied a case in which large periodic acid-Schiff-staining organisms were seen in the biopsy specimen from a necrotic bulla on the finger of a neutropenic patient with diffuse large cell lymphoma. The tissue biopsy specimen subsequently yielded a pure culture of B cereus. Staining with periodic acid-Schiff was then performed on a series of bacterial species in human tissue and from smears of culture colonies. The following bacterial species were found to be consistently periodic acid-Schiff positive after diastase digestion: B cereus, Corynebacterium diphtheriae, Propionibacterium acnes, Klebsiella pneumoniae, and Micrococcus luteus. PMID- 1900985 TI - Radioimmunoassay of carbonic anhydrase VI in saliva and sheep tissues. AB - A specific and sensitive radioimmunoassay has been developed for the measurement of the secreted carbonic anhydrase isoenzyme (CA VI) in sheep saliva and tissues. The assay can detect as little as 75 pg of CA VI, and the antibody used does not cross-react with CA II or CA III. The intra-assay variation, measured using a saliva sample, was 3.0%, whereas the inter-assay variation was 10.5%. The concentration of CA VI in parotid saliva from normal, resting sheep was 5.6 +/- 3.0 micrograms.ml-1 (n = 42) or 79.4 +/- 35.7 micrograms.mg of total protein-1. With feeding, the CA VI concentrations increased an average of 6-fold. The secretion rate of CA VI from the vascularly isolated neurotomized parotid gland of the anaesthetized sheep was 0.62 +/- 0.40 micrograms.min-1, compared with a rate of 11.7 +/- 7.8 micrograms.min-1 from the parotid gland of normal conscious sheep. Stimulation of the parotid-gland preparation by the muscarinic agent bethanechol increased the secretion rate to 438 +/- 172 microgram.min-1 (n = 8), and electrical stimulation of the secretomotor Moussu nerve increased CA VI secretion rate to 634 +/- 330 micrograms.min-1 (n = 4). Submandibular saliva from anaesthetized sheep contained 6.9 +/- 2.1 micrograms of CA VI.ml-1 (n = 3). The only tissues found to contain measurable amounts of CA VI were the parotid (6.4 micrograms.mg of protein-1) and submandibular (1.8 micrograms.mg of protein-1) salivary glands. The sublingual salivary gland, kidney, lung, adrenal, brain, skeletal muscle, liver, heart, pancreas, small intestine and cerebrospinal fluid did not have a measurable CA VI content. PMID- 1900986 TI - Okadaic acid identifies a phosphorylation/dephosphorylation cycle controlling the inhibitory guanine-nucleotide-binding regulatory protein Gi2. AB - Recently, the alpha-subunit of the inhibitory guanine-nucleotide-binding protein Gi2 (alpha-Gi2) has been shown to be a substrate for phosphorylation both by protein kinase C and also by other unidentified kinase(s) which are activated as a result of elevated cyclic AMP levels in intact rat hepatocytes [Bushfield, Murphy, Lavan, Parker, Hruby, Milligan & Houslay (1990) Biochem. J. 268, 449 457]. Here we show that the incorporation of [32P]Pi into alpha-Gi2 was enhanced 3-fold by incubation of intact hepatocytes with the tumour promoter and protein phosphatase (1 and 2A) inhibitor, okadaic acid. This action was both time- and concentration-dependent and was accompanied by a loss of guanine-nucleotide induced inhibition of adenylate cyclase. The increased labelling of alpha-Gi2 induced by okadaic acid was partially additive with that elicited by 8-bromo cyclic AMP, but not with that elicited by the protein kinase C activator phorbol 12-myristate 13-acetate. We suggest that, in the absence of hormones, the activity of alpha-Gi2 is under the control of a dynamic phosphorylation/dephosphorylation system involving protein kinase C and protein phosphatases 1 and/or 2A. This highlights the regulation of kinases and phosphatases as both providing potentially important mechanisms for causing 'cross-talk' between different signalling systems, in this instance controlling cellular responsiveness through regulation of alpha-Gi2 phosphorylation. PMID- 1900987 TI - The binding of D-gluconohydroximo-1,5-lactone to glycogen phosphorylase. Kinetic, ultracentrifugation and crystallographic studies. AB - Combined kinetic, ultracentrifugation and X-ray-crystallographic studies have characterized the effect of the beta-glucosidase inhibitor gluconohydroximo-1,5 lactone on the catalytic and structural properties of glycogen phosphorylase. In the direction of glycogen synthesis, gluconohydroximo-1,5-lactone was found to competitively inhibit both the b (Ki 0.92 mM) and the alpha form of the enzyme (Ki 0.76 mM) with respect to glucose 1-phosphate in synergism with caffeine. In the direction of glycogen breakdown, gluconohydroximo-1,5-lactone was found to inhibit phosphorylase b in a non-competitive mode with respect to phosphate, and no synergism with caffeine could be demonstrated. Ultracentrifugation and crystallization experiments demonstrated that gluconohydroximo-1,5-lactone was able to induce dissociation of tetrameric phosphorylase alpha and stabilization of the dimeric T-state conformation. A crystallographic binding study with 100 mM gluconohydroximo-1,5-lactone at 0.24 nm (2.4 A) resolution showed a major peak at the catalytic site, and no significant conformational changes were observed. Analysis of the electron-density map indicated that the ligand adopts a chair conformation. The results are discussed with reference to the ability of the catalytic site of the enzyme to distinguish between two or more conformations of the glucopyranose ring. PMID- 1900988 TI - Ontogeny of guanine-nucleotide-binding regulatory proteins in rabbit liver. AB - Ontogeny of trimeric GTP-binding regulatory proteins (G-proteins) and their subunits in rabbit liver during neonatal development was studied, by using bacterial-toxin-catalysed ADP-ribosylation of membrane proteins, immunoblot analysis to quantify the alpha-subunit (alpha s and alpha i) of stimulatory (Gs) and inhibitory (Gi) G-protein and the beta-subunit, and reconstitution assay with cyc- membranes (from Gs-deficient variant of S49 lymphoma cell) to measure Gs activity. Under optimal conditions of ADP-ribosylation, little cholera-toxin substrate (alpha s) was detected in membranes from liver of neonatal animals up to 24 h of age. Thereafter ribosylatable alpha s proteins, i.e. 45 kDa (alpha s 1) and 52 kDa (alpha s-2) proteins, were increasingly evident, reaching maximal levels in membranes from animals aged 4-6 weeks. The concentrations of alpha s-1 and alpha s-2, as determined by immunoblotting, were 6.1 +/- 0.8 and 2.7 +/- 0.4 pmol/mg of protein respectively at birth, and did not change during 0-24 h after birth. Thereafter they gradually increased to maximal levels of 22.1 +/- 1.3 and 10.5 +/- 0.7 pmol/mg of protein for alpha s-1 and alpha s-2 respectively, within 6 weeks. The beta-subunit also showed a similar 3-4-fold increase during the same age span. In contrast, the pertussis-toxin substrate (alpha i) was clearly evident even in membranes from term animals and in all age groups studied. Its developmental pattern, as assessed by ADP-ribosylation, was the same as that determined by immunoblot analysis. The functional activity of Gs in cholate extracts of membranes exhibited similar developmental pattern to that of cholera toxin-mediated labelling. This activity also paralleled the concentrations of alpha s as measured by immunoblotting. These results suggest differential expression of G-protein subunits in liver during neonatal development. PMID- 1900990 TI - Does MAP1B bind to tubulin through the interaction of alpha-helices? PMID- 1900989 TI - 2,3-di-O-tetradecyl-1-O-(beta-D-glucopyranosyl)-sn-glycerol is a substrate for human glucocerebrosidase. AB - Glucocerebrosidase, the lysosomal enzyme that is deficient in patients with Gaucher's disease, hydrolyses non-physiological aryl beta-D-glucosides and glucocerebroside, its substrate in vivo. We document that 2,3,-di-O-tetradecyl-1 O-(beta-D-glucopyranosyl)-sn-glycerol (2,3,-di-14:0-beta-Glc-DAG) inhibits human placental glucocerebrosidase activity in vitro (Ki 0.18 mM), and the nature of inhibition is typical of a mixed-type pattern. Furthermore, 2,3-di-14:0-beta-Glc DAG was shown to be an excellent substrate for the lysosomal beta-glucosidase (Km 0.15 mM; Vmax. 19.8 units/mg) when compared with the natural substrate glucocerebroside (Km 0.080 mM; Vmax. 10.4 units/mg). The observations that (i) glucocerebrosidase-catalysed hydrolysis of 2,3-di-14:0-beta-Glc-DAG is inhibited by conduritol B epoxide and glucosylsphingosine, and (ii) spleen and brain extracts from patients with Gaucher's disease are unable to hydrolyse 2,3-di-14:O beta-Glc-DAG demonstrate that the same active site on the enzyme is responsible for catalysing the hydrolysis of 4-methylumbelliferyl beta-D-glucopyranoside, glucocerebroside and 2,3-di-14:O-beta-Glc-DAG. With the aid of computer modelling we have established that the oxygen atoms in 2,3-DAG-Glc at the C-1, C-4*, C-5* (the ring oxygen in glucose) and C-2 positions correspond topologically to the oxygens at C-1, C-4* and C-5* and the nitrogen atom attached to C-2 respectively in glucocerebroside (* signifies a carbon atom in glucose); furthermore, all of the distances with respect to overlap of corresponding heteroatoms range from 0.02 A to 0.77 A (0.002-0.077 nm). A root-mean-square deviation of 0.31 A (0.031 nm) was obtained when the energy-minimized structures of 2,3-di-14:O-beta-Glc-DAG and glucocerebroside were compared using the latter four heteroatom co-ordinates. PMID- 1900991 TI - Mechanisms controlling lactational infertility. AB - Despite the important role breastfeeding plays in regulating a mother's fertility, the mechanisms controlling lactational infertility remain to be fully elucidated. Breastfeeding suppresses fertility for a period which varies widely among individuals and within different communities. Suckling stimulus is the key factor in controlling the duration of infertility. Suckling by the infant appears to inhibit luteinizing hormone secretion by inhibiting the pulsatile release of gonadotrophin-releasing hormone from the hypothalamus. The exact mechanism remains unclear but a suckling-induced increase in hypothalamic opioid tone may be involved. Prolactin does not appear to play a major role, other than being essential for maintenance of milk production, in lactational infertility. PMID- 1900992 TI - The vitelline coat spikes: a new peculiar structure of Mytilus galloprovincialis eggs with a role in sperm-egg interaction. AB - In the course of this study we found that in Mytilus galloprovincialis eggs long filamentous protrusions never described before, which we have termed "vitelline coat spikes," could be clearly detected using the lectin from Dolichos biflorus, which recognizes the GalNAc residues. The spikes could be also observed by transmission electron microscope but only in some fortuitous sections could their origin in the vitelline coat be clearly observed. The spikes were also clearly visible using the scanning electron microscope. Observations of the sperm-egg interaction very few seconds after insemination or using fixed eggs suggested that the spikes could play a role in a primary binding to the unreacted sperm. Experiments have been done to test the effect of GalNAc on the sperm-egg binding and on the fertilization process which seem to confirm this hypothesis. PMID- 1900993 TI - Unusual expired carbon dioxide waveform. PMID- 1900994 TI - Blind oral intubation directed by capnography. PMID- 1900995 TI - The apnea-PaCO2 relationship--unanswered questions? PMID- 1900997 TI - Changing disease patterns in AIDS. PMID- 1900996 TI - Virus infection relevant to dental staff. PMID- 1900998 TI - Peat Marwick McLintock. A vision for the future. PMID- 1900999 TI - Crisis in the Gulf. The right treatment. PMID- 1901000 TI - 'Caring for Romania Appeal'. A new beginning. PMID- 1901001 TI - The place of Eusol in wound management. AB - This article by Stephen Farrow and Ben Toth presents a summary of a report on the place of Eusol in wound management commissioned by the Regional Nursing Advisory Committee of the Southwestern Regional Health Authority. An extensive literature search was undertaken to try and establish the applicability of the product. Although there are gaps in the available research, the report concluded that Eusol should not be applied to wounds. PMID- 1901002 TI - Asystole, ventricular fibrillation and standstill. PMID- 1901003 TI - Waiting for the catch. PMID- 1901004 TI - Nursing research at Rampton Hospital. AB - The growth of nursing research activity in Rampton Hospital is outlined in this paper. David Robinson, who has held the position of Nurse Researcher in the hospital since 1986, describes the evolution of the post and how the introduction of English National Board courses related to research have excited great interest among nursing staff. Work is currently underway to establish the effect the rise in research projects has had on practice, with initial results providing grounds for optimism. PMID- 1901006 TI - Points of view. PMID- 1901005 TI - Developing the new practitioner. AB - In the second part of this series on issues in ward management facing charge nurses, Claire Hale examines the role of the charge nurse in relation to three areas which are fundamental to Project 2000: the supernumerary status of students, the linking of theory to practice and the provision of a suitable learning environment. With the success or otherwise of the new courses depending to such a large extent on the enthusiasm and co-operation of charge nurses, the author suggests a number of tangible 'rewards' which may be offered in recognition of their efforts. PMID- 1901007 TI - Crimes of compassion. PMID- 1901008 TI - The tables turned. PMID- 1901009 TI - Sexist language--why fuss? PMID- 1901010 TI - Policy results in 'false prison figures' for HIV. PMID- 1901011 TI - International Council of Nurses. Playing a vital role. Interview by Derek Hand. PMID- 1901012 TI - The wounds of war. PMID- 1901013 TI - Scottish excellence. The strategy at work. PMID- 1901014 TI - Complementary therapy in practice. AB - Dorothy Crowther describes the evolution of the Wirral Holistic Care Services, a company dedicated to helping people cope with cancer. Based on a recognition that such patients want more than the standard NHS fare, initial evaluations suggest that the company is going some way to meeting the extra needs of this group. Available therapies include aromatherapy, kinesiology, reflexology and meditation, incorporating a model of care which endorses putting the patient first. PMID- 1901016 TI - Points of view. PMID- 1901015 TI - No pain, no gain? PMID- 1901017 TI - Sleepless nights. PMID- 1901018 TI - Working mothers. Tax relief--the answer? PMID- 1901019 TI - Influence of local anesthetics on ventilation. AB - Local anesthetics (lidocaine, mepivacaine or bupivacaine) were given as an intravenous infusion to 18 volunteers to study the influence of these drugs on resting ventilation (breathing air) and stimulated ventilation (hypercarbia- or hypoxemia-induced). Control measurements were made of resting ventilation and stimulated ventilation prior to the infusion. The ventilatory measurements were repeated during the latter half of the infusion, when plasma concentrations of these agents were considered to be near steady-state levels (mean plasma levels of lidocaine, mepivacaine and bupivacaine, 3.1 micrograms/ml, 2.7 micrograms/ml and 1.5 micrograms/ml, respectively) and within a range normally achieved clinically. None of the drugs tested affected resting ventilation or ventilation stimulated by hypercarbia. The drugs tested exerted a slight stimulatory effect on ventilation during hypoxemia. PMID- 1901020 TI - Preparation of the Fv fragment from a short-chain mouse IgG2a anti-dansyl monoclonal antibody and use of selectively deuterated Fv analogues for two dimensional 1H NMR analyses of the antigen-antibody interactions. AB - The Fv fragment, a univalent antigen-binding unit with a molecular weight of 25,000, has successfully been prepared in high yield by limited proteolysis with clostripain of a short-chain mouse IgG2a anti-dansyl monoclonal antibody in which the entire CH1 domain is deleted [Igarashi, T., Sato, M., Takio, K., Tanaka, T., Nakanishi, M., & Arata, Y. (1990) Biochemistry 29, 5727-5733]. The Fv fragment obtained is stable at room temperature and retains its full antigen-binding capability. It has been shown that selective deuterium labeling of the Fv fragment, which is half the size of the Fab fragment, provides 1H NMR spectral data at a sufficient resolution for a detailed structural analysis of the antigen combining site. NOESY spectra of an Fv analogue, in which all aromatic protons except for His C2'-H and Tyr C3',5'-H had been deuterated, were measured in the presence of varying amounts of dansyl-L-lysine. On the basis of the NOESY data obtained, it was possible to assign all the ring proton resonances for the dansyl group that is bound to the Fv fragment. It was also possible to obtain information about His and Tyr residues of the Fv fragment in the absence and presence of the antigen. On the basis of the NMR data obtained, we have shown that at least two Tyr residues along with one of the amide groups are directly involved in antigen binding. The mode of interaction of the dansyl ring with these residues in the Fv fragment has briefly been discussed. PMID- 1901021 TI - Functional water channels and proton pumps are in separate populations of endocytic vesicles in toad bladder granular cells. AB - Functional water channels are retrieved by endocytosis from the apical membrane of toad bladder granular cells in response to vasopressin [Shi, L.-B., & Verkman, A.S. (1989) J. Gen. Physiol. 94, 1101-1115]. To examine whether endocytic vesicles which contain the vasopressin-sensitive water channel fuse with acidic vesicles for entry into a lysosomal pathway, ATP-dependent acidification and osmotic water permeability were measured in endosomes from control bladders and bladders treated with vasopressin (VP) and/or phorbol myristate acetate (PMA). Endosomes were labeled with the fluid-phase markers 6-carboxyfluorescein or fluorescein-dextran. Osmotic water permeability (Pf) was measured by stopped-flow fluorescence quenching and proton ATPase activity by ATP-dependent, N ethylmaleimide-inhibitable acidification. In a microsomal pellet, Pf was low (less than 0.002 cm/s, 20 degrees C) in labeled endocytic vesicles from control bladders but high (0.05-0.1 cm/s) in a subpopulation (50-70%) of vesicles from VP and PMA-treated bladders. Following ATP addition, the average drop in pH was 0.1 (control), 0.3 (VP), and 0.2 (PMA) unit. Measurement of pH in individual endocytic vesicles by quantitative image analysis showed that less than 20% of vesicles from VP-treated bladders acidified by greater than 0.5 pH unit. To examine whether water channels and proton pumps were present in the same endocytic vesicles, the pH of endosomes with high and low water permeability was measured from the effect of ATP on the amplitude of the fluorescence quenching signal in response to an osmotic gradient.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1901022 TI - A homologue of a nuclear-coded iron-sulfur protein subunit of bovine mitochondrial complex I is encoded in chloroplast genomes. AB - The chloroplast genomes of Marchantia polymorpha, Nicotiana tabacum, and Oryza sativa contain open reading frames (ORFs or potential genes) encoding homologues of some of the subunits of mitochondrial NADH:ubiquinone oxidoreductase (complex I). Seven of these subunits (ND1-ND4, ND4L, ND5, and ND6) are products of the mitochondrial genome, and two others (the 49- and 30-kDa components of the iron sulfur protein fraction) are nuclear gene products. These findings have been taken to indicate the presence in chloroplasts of an enzyme related to complex I, possibly an NAD(P)H:plastoquinone oxidoreductase, participating in chlororespiration. This view is reinforced by the present work in which we have shown that chloroplast genomes encode a homologue of the 23-kDa subunit, another nuclear-encoded component of bovine complex I. The 23-kDa subunit is in the hydrophobic protein fraction of the enzyme, the residuum after removal of the flavoprotein and iron-sulfur protein fractions. The sequence motif CysXXCysXXCysXXXCysPro, which provides ligands for tetranuclear iron-sulfur centers in ferredoxins, occurs twice in its polypeptide chain and is evidence of two associated 4Fe-4S clusters. This is the only iron-sulfur protein identified so far in the hydrophobic protein fraction of complex I, and so it is possible that one of these centers is that known as N-2, the donor of electrons to ubiquinone. The sequence of the 23-kDa subunit is closely related to potential proteins, which also contain the cysteine-rich sequence motifs, encoded in the frxB ORFs in chloroplast genomes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1901023 TI - Mapping and modification of an antibody hapten binding site: a site-directed mutagenesis study of McPC603. AB - The quantitative contributions of various amino acid residues to hapten binding in the Fv fragment of the antibody McPC603 were investigated by site-directed mutagenesis. The three-dimensional structure of the Fab' fragment of McPC603 is known to atomic resolution. The haptens phosphocholine, choline sulfate, 3 (trimethylammonium)propane-1-sulfonate, 4-(trimethylammonium)butyric acid, and 4 (trimethyl-ammonium)butyric acid methyl ester were tested for binding. It was found that the phosphate group but not the sulfate and sulfonate groups, interacts with the hydroxyl group of Tyr33(h). The required positive charge for the binding of the phosphate must be contributed by Arg52(h); a lysine at this position or an additional positive charge at position 33(h) abolishes the binding to a phosphocholine affinity column. The interaction between Tyr100(l) and Glu35(h) was found to be essential and could not be functionally replaced by any other pair of residues tested. Binding of the quaternary ammonium ion needs a negative charge; it can reside in either Asp97(l) or Asp101(h), but both together prevent binding to the affinity column. These data may serve as the basis for the development of quantitative treatments of antigen-antibody interactions. PMID- 1901024 TI - Sexually transmitted disease treatment and return for test of cure of adolescents in a family planning clinic. AB - This retrospective study assessed the return for treatment and test-of-cure rates for gonorrhea and chlamydial infection among 154 adolescents and young adults attending a family planning clinic. Eighty-four percent returned for treatment and 57% of those returned for a test of cure. No statistical differences in race/ethnicity, marital status, gravida, age, presence of symptoms, or type of infection were found between those returning and those not returning for treatment. Issues associated with sexually transmitted disease treatment and follow-up in the family planning clinic setting are discussed. PMID- 1901026 TI - Biochemical demonstration of endocytosis and subsequent resecretion of high density lipoprotein by rat peritoneal macrophages. AB - To investigate the post-binding events of high-density lipoprotein (HDL), rat peritoneal macrophages were enriched by collagen gel-coated plates and incubated in a cell-suspension system with fluorescein isothiocyanate-labeled HDL (FITC HDL), followed by fluorescence spectroscopic analyses. Upon incubation with FITC HDL at 37 degrees C for 30 min, the microenvironmental pH of the cell-associated FITC-HDL was 6.50, whereas a 0 degree C-incubation gave a corresponding pH of 7.15. Carbonyl cyanide m-chlorophenylhydrazone, a protonophore known to dissipate the proton gradient, restored the former acidic pH (pH 6.40) to pH 7.20, but had no effect on the latter. This indicates that cell surface-bound HDL is internalized and exposed to an acidic compartment. When cells were incubated with FITC-HDL at 37 degrees C for 30 min and the cell-associated FITC-HDL was chased at 37 degrees C, the fluorescence intensity at 490 nm showed a time-dependent increase. This increase was explained by a release of endocytosed FITC-HDL into the extracellular medium but not by a simple outward dissociation of the cell associated FITC-HDL. The microenvironmental acidic pH of the cell-associated FITC HDL changed to a less acidic pH during the chase whereas that of FITC-HDL became constant after released into the medium, indicating that endocytosed HDL was resected back into the extracellular medium. This resection process was temperature-dependent and accelerated by HDL itself. These results provide the biochemical evidence for the presence of an endocytic-exocytic pathway for HDL in rat peritoneal macrophages. PMID- 1901025 TI - Differences in high-energy phosphate catabolism between the rat and the dog in a heart preservation model. AB - Concentrations of ATP and creatine phosphate were measured in rat and dog hearts preserved either by cold storage (procedure A) or by continuous hypothermic perfusion (procedure B). In procedure A (3 dogs, 4 rats) the hearts were normothermically excised without cardioplegia and were stored in 0.9% NaCl at 0.5 degrees C; in procedure B (6 dogs, 21 rats) hypothermic cardioplegic arrest was performed, and then the hearts were retrogradely perfused through the aorta for 24 hours with use of an oxygenated Bretschneider cardioplegic solution at 2 degrees to 4 degrees C. Whole rat hearts were frozen using Wollenberger clamps at desired times during the preservation period; transmural needle biopsy specimens were sampled from dog hearts. In control nonpreserved hearts, the ATP and creatine phosphate were as follows (mean +/- SD): 26.7 +/- 4.1 and 27.1 +/- 10.3 mumol/gm dry weight, respectively (dog hearts), and 23.1 +/- 2.1 and 34.2 +/- 12.1 mumol/gm dry weight, respectively (rat hearts). With procedure A, ATP decreased by 36% in dog hearts and by 64% in rat hearts during the first hour of storage. By 24 hours, only 6% of the ATP remained in the dog hearts and 1% in the rat hearts. Creatine phosphate decreased by 85% (dog hearts) and by 93% (rat hearts) during the first hour of storage. The ATP and creatine phosphate values observed in rat hearts after 1 hour of procedure A preservation were significantly lower than in dog hearts (p less than 0.05). With procedure B, cardioplegic arrest by itself did not alter high-energy phosphate concentrations in dog or rat hearts.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1901027 TI - Hydroxyarchaetidylserine and hydroxyarchaetidyl-myo-inositol in Methanosarcina barkeri: polar lipids with a new ether core portion. AB - Lipids of the methanogenic archaebacterium, Methanosarcina barkeri were analyzed. The lipid content was 5.4% of dry cell and polar lipids comprised 87% of the total lipid. Polar lipids were separated into 14 spots by two-dimensional thin layer chromatography. These were six phospholipids, seven aminophospholipids and one glycolipid, of which two phospholipids and two aminophospholipids were major constituents. After removal of polar head groups from total lipids, two kinds of glycerol diether core lipids were found. One was 2,3-di-O-phytanyl-sn-glycerol (archaeol) and the other 2-O-(3'-hydroxy-3', 7', 11', 15'-tetramethyl)hexadecyl-3 O-phytanyl-sn- glycerol (hydroxyarchaeol). Those structures were identified on the basis of chemical analysis, fast atom bombardment spectrometry, gas-liquid chromatography-mass spectrometry and 1H- and 13C-NMR spectrometry. The latter was a new core lipid which was different from hydroxyarchaeol of Methanothrix concilii. The hydroxyarchaeol core lipid comprised 60% of polar lipid in M. barkeri. The structures of core lipids are quite different from those previously reported by De Rosa et al. (Biochim, Biophys. Acta (1986) 875, 487-492) concerning M. barkeri lipids. The structures of two major polar lipids, both of which had hydroxyarchaeol as core proteins, were elucidated. These lipids were 2 O-(3'-hydroxy)phytanyl-3-O-phytanyl-sn-glycero-1-phosphoserine (hydroxyarchaetidylserine) and 2-O-(3'-hydroxy)phytanyl-3-O-phytanyl-sn- glycerol phospho-myo-inositol (hydroxyarchaetidyl-myo-inositol). Archaetidylserine and archaetidylinositol, which had the usual archaeol core portion, were also present as minor polar lipids. PMID- 1901028 TI - Apolipoprotein A-I gene expression in transgenic mice. PMID- 1901029 TI - Diabetic ketoacidosis. AB - Diabetic ketoacidosis (DKA) remains a significant clinical problem because there is considerable morbidity and mortality associated with the condition. Although prevention of DKA remains a major focus in diabetic patients, it is apparent that critical care personnel will continue to be exposed to the acute complications. It is important that critical care personnel have training in the management of DKA so as to rapidly stabilize the patient, begin appropriate medical treatment, and initiate the work-up to identify precipitating factors. Only then will the mortality and morbidity associated with DKA be reduced. PMID- 1901030 TI - In vitro immunomodulating effect of protein-bound polysaccharide, PSK on peripheral blood, regional nodes, and spleen lymphocytes in patients with gastric cancer. AB - PSK, a protein-bound polysaccharide, has been widely used for cancer immunotherapy in Japan. However, the mechanism of its immunomodulatory effect has not been fully clarified. In the present study the in vitro effect of PSK on the lymphocytes of patients with gastric cancer was studied. Culturing lymphocytes with PSK at 5-100 micrograms/ml increased the level of DNA synthesis, and augmented the cytotoxicities against K562 and KATO-3. Flow-cytometric analysis also showed an increase in the proportion of interleukin-2 (IL-2)-receptor positive cells after the lymphocytes were cultured with PSK. However the cytotoxicity of cells cultured with PSK was not augmented by the addition of recombinant interferon gamma (rIFN gamma) and rIL-2. Further experiments using fractionated PSK showed that its biological action is present mainly in fractions having molecular masses greater than 10(5) Da. However, these immunomodulations were not seen in all patients. These results suggest that the susceptibility of lymphocytes to PSK may be different in each patients, and that the immunomodulation by PSK may be mediated by mechanisms independent of IFN and IL 2. PMID- 1901031 TI - Phorbol ester-induced enhancement in lytic activity of CD8+ splenic T cells from low-dose melphalan-treated MOPC-315-tumor bearers. AB - We have previously shown that while spleen cells from untreated mice bearing a large MOPC-315 tumor are not cytotoxic in vitro for MOPC-315 tumor cells, spleen cells obtained from such mice on day 7 after low-dose melphalan (L-phenylalanine mustard); L-PAM therapy exert a substantial anti-MOPC-315 cytotoxicity [Mokyr et al. (1989) Cancer Res 49: 4597]. Here we show that this anti-MOPC-315 lytic activity is evident by day 5, and peaks on day 7 after the low-dose chemotherapy, at a time when the mice are actively engaged in tumor eradication. Short-term exposure of spleen cells from mice bearing a MOPC-315 tumor and treated with low dose L-PAM (L-PAM TuB mice) to phorbol 12-myristate 13-acetate (PMA) was found to enhance greatly the ability of these spleen cells to lyse MOPC-315 tumor cells. The highest level of anti-MOPC-315 cytotoxicity was obtained when spleen cells from tumor-bearing mice that had received chemotherapy 7 days earlier were exposed to PMA at a concentration of 1-10 ng/ml. The exertion of the enhanced anti-MOPC-315 lytic activity by L-PAM TuB spleen cells exposed to PMA was found to require CD8+, but not CD4+, T cells. The apparent specificity of the lytic activity exerted by the PMA-stimulated L-PAM TuB spleen cells was illustrated not only by the inability of the spleen cells to lyse an allogeneic, antigenically unrelated thymoma (EL4), but also by their relatively weak lytic activity for two antigenically related syngeneic plasmacytomas. In addition, when EL4 target cells were admixed with MOPC-315 tumor cells, the lytic activity triggered in the L-PAM TuB spleen cells by the MOPC-315 tumor cells plus PMA was not effective in lysing the antigenically unrelated target cells. Moreover, even in the presence of the calcium-specific ionophore, ionomycin, L-PAM TuB spleen cells exposed to PMA were unable to lyse the EL4 target cells. Thus, fresh CD8+ splenic T cells from L-PAM TuB mice that are in the process of eradicating a large MOPC-315 tumor as a consequence of low-dose L-PAM therapy can be triggered with PMA to exert enhanced lytic activity against MOPC-315 tumor cells.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1901034 TI - The effect of contact lens wear on tear immunoglobulins. AB - We assayed tear immunoglobulins (IgA, IgG, and IgM) by radial immunodiffusion in 24 contact lens wearers and 22 healthy control subjects. IgA level was found to be increased (P less than or equal to 0.02) in rigid contact lens wearers (mean: 0.14 +/- 0.07 g/L) compared to control subjects (mean: 0008 +/- 0.06 g/L). IgA levels of both of PMMA contact lens wearers (mean: 0.14 +/- 0.08 g/L; P less than or equal to 0.05) and rigid gas permeable contact lens wearers (mean: 0.13 +/- 0.07 g/L; P less than or equal to 0.05) were increased in comparison with the control group. No statistically significant differences were found in IgA levels of various types of soft contact lens wearers or in IgG or IgM levels between wearers and controls. The mean duration of lens wear was 6.4 years (range: 1-20 years), and an increase in IgG level was found, related length of lens wear (P less than or equal to 0.03). We believe that the continuous mechanical stimulation of conjunctiva alters the level of tear immunoglobulins, especially the IgA type. PMID- 1901033 TI - Selectivity of juxtaposition between cup-shaped lactotrophs and gonadotrophs from rat anterior pituitary in culture. AB - Semi-thin sections of three-dimensional reaggregates from adult female rat pituitary, cultured in serum-free defined medium, were stained for prolactin, gonadotropin, thyrotropin, growth hormone and S-100, using the double immunolabelling technique. The frequency of juxtaposition between lactotrophs and gonadotrophs was enumerated and compared with the expected frequency at random distribution of polygonal cell profiles in a hexagonal configuration. The proportions of lactotrophs and gonadotrophs in the aggregate sections were determined using stereometrical analysis. The observed frequency of juxtaposition did not differ significantly from the expected frequency. Hence, no reason was found to assume a selective adhesion between lactotrophs and gonadotrophs in adult female rat pituitary reaggregates. A constant proportion of lactotrophs was found to meet the criteria of a cup-shaped morphology, and 70% +/- 9% (mean +/- S.D.) of these so-called cup-shaped lactotrophs were found to be juxtaposed at their concave side to gonadotrophs. Administration of 0.01 nM 17 beta-oestradiol to the culture medium resulted in a significant reduction of the proportion of cup-shaped lactotrophs but did not affect the selectivity of juxtaposition to gonadotrophs. The selectivity of juxtaposition between cup-shaped lactotrophs and gonadotrophs may be the morphological correlate of the functional relationship between these cells, which are known to be involved in an intra-pituitary paracrine communication system. PMID- 1901032 TI - Cytochalasin-B-induced immunosuppression of murine allogeneic anti-tumor response and the effect of recombinant human interleukin-2. AB - Cytochalasin B (CB), administered i.p. to C57B1/6 mice in a single dose as a suspension in carboxymethylcellulose 2%/Tween 20 1%, inhibits in a dose-dependent and time-dependent manner the ability of spleen cells to respond to allogeneic P815 mastocytoma tumor cells in vitro. Spleen cells from CB-treated animals sensitized to X-irradiated P815 cells in 4-day cultures at a 50:1 responder:stimulator ratio and tested for specific cytotoxicity against 51Cr labelled P815 target cells showed strong inhibition 3 h after CB treatment at a dose of 50 mg/kg. A dose of 25 mg/kg showed measureable but not statistically significant inhibition at 3 h, whereas 10 mg/kg produced only slight inhibition, and 5 mg/kg and 2 mg/kg were noninhibitory. None of the doses produced significant suppression 19 h or 72 h after CB treatment. Addition to the sensitization cultures of human recombinant interleukin-2 (rhIL-2) at 350 BRMP units/ml completely restored tumor lytic capacity. C57B1/1 mice treated with CB 50 mg/kg, i.p. and challenged i.p. with 3 x 10(7) allogeneic P815 mastocytoma cells showed a brief, time-dependent, statistically significant abrogation of allogeneic responsiveness consistent with transient reversible immunosuppression within 3-12 h following CB treatment. No such inhibition of host allogeneic responsiveness in vivo was observed when CB was administered 24 h prior to, simultaneously with, or 1, 2, or 4 days after tumor challenge. Thus CB at the highest tolerated i.p. dose in vivo causes only a transient inhibition of anti allo-responsiveness measured in culture, and rhIL-2 used in vitro restores lytic capacity. The anti-allo effect of CB is also seen to be transient directly in vivo since allogeneic tumor outgrowth is permitted for only a brief period following administration of CB. These results indicate that the use of CB in vivo in anti-tumor chemotherapy protocols will not be complicated by profound or prolonged immunosuppressive effects. PMID- 1901035 TI - Investigations on etiology of Crohn's disease. Humoral immune response to stress (heat shock) proteins. AB - Many investigators have tried to prove a relationship between Crohn's disease and Mycobacteria. Recent evidence suggests that some autoimmune diseases may be initiated through "molecular mimicry" between mycobacterial stress protein antigens and their human homologs. We investigated whether antibody to stress proteins was more frequent in patients with Crohn's disease than controls. We used ATP binding to separate stress proteins (heat-shock-induced, de novo synthesized, and constitutively expressed ATP-binding proteins) from crude extracts obtained from Mycobacteria and from an SV40-transformed human epithelial cell line that expresses a heat-shock protein, hsp73, as a complex with SV40 T antigen. We used immunoblots to compare sera from 34 patients with Crohn's disease, 14 with ulcerative colitis, and 14 with duodenal or gastric ulcers (noninflammatory bowel disease control patients). We found no statistically significant pattern or frequency of antibodies against single proteins or a combination of mycobacterial or human stress proteins. These observations do not support the hypothesis that a humoral immune response to stress proteins of Mycobacteria is important in the pathogenesis of Crohn's disease. PMID- 1901037 TI - Effect of deletion of the A1 domain of von Willebrand factor on its binding to heparin, collagen and platelets in the presence of ristocetin. AB - In order to study the functional importance of the collagen, heparin and glycoprotein-Ib-binding domain, we deleted the A1 domain of von Willebrand factor (vWF), corresponding to residues 478-716, by oligonucleotide-directed mutagenesis. The resulting delta A1-vWF cDNA was expressed in COS-1 monkey kidney cells and compared to wild-type vWF. The higher-molecular-mass multimers were decreased in delta A1 recombinant von Willebrand factor (delta A1-rvWF) compared to plasma vWF and rvWF. The reactivity of delta A1-rvWF and rvWF with monoclonal antibodies directed against the collagen-binding domain (residues 969-992), the vessel-wall-binding domain, and the binding site for glycoprotein IIb-IIIa on platelets was identical. The interaction with vWF of the monoclonal antibody directed against the glycoprotein Ib binding domain was abolished for delta A1 rvWF, and similar to plasma vWF for rvWF. The binding of factor VIII to delta A1 rvWF and rvWF was similar. delta A1-rvWF and rvWF bound similarly to collagen, but the binding of delta A1-rvWF to heparin and to platelets in the presence of ristocetin were abolished. These data indicate that the heparin-binding site in the A1 domain is essential. There is no second binding domain for glycoprotein Ib outside the A1 domain. The collagen-binding domain in the A1 domain is either not active or its action can be compensated by the second collagen-binding domain. PMID- 1901036 TI - Vagal amplification of phrenic nerve activity at different levels of ventilation in spontaneously breathing cats. AB - The vagal amplification of phrenic nerve activity (APHR) was studied as a function of minute ventilation (VE) in 12 spontaneously breathing, anaesthetized cats. Increasing levels of VE were obtained by repeated venous administrations of 2,4-dinitrophenol. The APHR was obtained from the ratio of the phrenic nerve activities in a normal and in an occluded breath. The APHR is thought to be mediated by slowly and/or rapidly adapting stretch receptors. Because airway CO2 may inhibit the discharge of these receptors, we also investigated the influence on APHR of adding 1% and 2% by volume of CO2 to inspired gas. The results showed that an increase in VE had no influence on APHR. The values of APHR ranged from 0.95 to 1.31 and were on average 1.08. Low levels of CO2 in inspired gas did not influence APHR. Our findings suggest that the vagal amplification of central inspiratory output as determined from phrenic nerve activity has a constant gain and it seems to play a relatively unimportant role in sustaining hyperpnoeic breathing. PMID- 1901038 TI - Chemical modification and 1H-NMR studies on the receptor-binding region of human interleukin 6. AB - Oxidation of the Met residues of human interleukin 6 (IL-6) molecule has been performed. Reactivity of Met for the oxidation reaction was found to decrease in the order of Met50, Met118, Met185, Met162, and Met68. Chemical modifications involving oxidation and carboxypeptidase A digestion of IL-6 have led to the assignments of the methyl proton resonances of Met162 and Met185, respectively. The hydroxynitrobenzyl chromophore attached to Trp158 in the IL-6 molecule showed a different absorption spectrum when the labeled IL-6 was bound to the soluble IL 6 receptor. This result indicates that Trp158 is near the receptor-binding region in IL-6. On the basis of the 1H-NMR and chemical modification data, it has been concluded that Trp158 is in spatial proximity to Met162, His165 and Met185. The receptor-binding activity decreased with an increase in the number of oxidized Met residues. Of these five Met residues, Met162 was the residue in which the receptor-binding activity decreased in the most parallel degree with that of the oxidation reaction. PMID- 1901039 TI - Purification and characterisation of plasminogen activator inhibitor 2 produced in Saccharomyces cerevisiae. AB - Expression of plasminogen activator inhibitor 2 (PAI-2) under the control of the protease B gene promoter in a mutant strain of Saccharomyces cerevisiae, DS569, resulted in its accumulation intracellularly at up to 20% of the soluble cell protein. Provision of an N-terminal signal sequence resulted in the secretion of a hyperglycosylated molecule. The intracellularly produced PAI-2 was purified by copper-chelate and anion-exchange chromatography to greater than 95% pure and was fully active. The recombinant PAI-2 formed SDS-stable complexes with urokinase and tissue-type plasminogen activator and inhibited the proteases with similar reaction kinetics to placental PAI-2 (second-order rate constant for uPA, 2.4 x 10(6) M-1 s-1, and for two-chain tPA, 0.7 x 10(5) M-1 s-1). As is the case for placental PAI-2, the N-terminus of the yeast-derived recombinant PAI-2 was blocked. The high productivity and consequent ease of purification mean that S. cerevisiae provides an excellent source of recombinant PAI-2 for investigation of its therapeutic potential in the treatment of neoplastic and inflammatory diseases. PMID- 1901040 TI - Glutamate dehydrogenase from the thermoacidophilic archaebacterium Sulfolobus solfataricus. AB - An NAD(P)-dependent glutamate dehydrogenase was purified to homogeneity from the thermoacidophilic archaebacterium Sulfolobus solfataricus. The enzyme is a hexamer (subunit mass 45 kDa) which dissociates into lower states of association when submitted to gel filtration. Isoelectric focusing analysis of the purified enzyme showed a pI of 5.7 and occasionally revealed microheterogeneity. The enzyme is strictly specific for the natural substrates 2-oxoglutarate and L glutamate, but is active with both NADH and NADPH. S. solfataricus glutamate dehydrogenase revealed a high degree of thermal stability (at 80 C the half-life was 15 h) which was strictly dependent on the protein concentration. Very high levels of glutamate dehydrogenase were found in this archaebacterium which suggests that the conversion of 2-oxoglutarate and ammonia to glutamate is of central importance to the nitrogen metabolism in this bacterium. PMID- 1901041 TI - Separation of the poly(glycerophosphate) lipoteichoic acids of Enterococcus faecalis Kiel 27738, Enterococcus hirae ATCC 9790 and Leuconostoc mesenteroides DSM 20343 into molecular species by affinity chromatography on concanavalin A. AB - This study shows for the first time microheterogeneity of 1,3-linked poly(glycerophosphate) lipoteichoic acids. The lipoteichoic acids investigated were those of Enterococcus faecalis Kiel 27738 (I), Enterococcus hirae (Streptococcus faecium) ATCC 9790 (II), and Leuconostoc mesenteroides DMS 20343 (III). Lipoteichoic acids II and III are partially substituted by mono-, di-, tri , and tetra-alpha-D-glucopyranosyl residues with (1----2) interglycosidic linkages. Lipoteichoic acid I is substituted with alpha-kojibiosyl residues only. Lipoteichoic acids I and III additionally carry D-alanine ester. Lipoteichoic acids were separated on columns of concanavalin-A-Sepharose according to their increasing number of glycosyl substituents per chain. It was evident that all molecular species are usually glycosylated and that alanine ester and glycosyl residues occur on the same chains. The chain lengths of lipoteichoic acid I and II vary between 9-40 glycerophosphate residues, whereas those of lipoteichoic acid III appear to be uniform (33 +/- 2 residues). Molecular species differ in the extent of glycosylation but their content of alanyl residues is fairly constant. All lipoteichoic acids contain a small fraction (5-15%) different in composition from the bulk and most likely reflecting an early stage of biosynthesis. Two procedures for chain length determination of poly(glycerophosphate) lipoteichoic acids are described. PMID- 1901042 TI - Serum prolactin levels in patients treated with a gonadotropin-releasing hormone analogue for adenocarcinoma of the prostate. AB - Twenty-six patients with advanced cancer of the prostate were treated with [D SER(BUt)6]LHRH-(1-9) nonapeptide ethylamide (buserelin). All but 6 patients evidenced signs of metastasis. Blood prolactin levels were measured prior to the initiation of treatment and during a follow-up period of 18 months. A statistically significant (p greater than 0.0005) elevation in serum prolactin levels was observed after 3 months of treatment. Serum prolactin remained elevated for a total of 6 months, after which a decline to pretreatment levels was observed. Our observation of a transient rise in prolactin levels during the chronic administration of buserelin is at variance with previously published data which reported unchanged prolactin levels during such treatment. PMID- 1901043 TI - Studies on bone marrow cells in experimental animals: bone marrow testing in the safety study. PMID- 1901044 TI - The possible role of LTC4 in the pathogenesis of ethanol-induced gastric lesions in mice and their prevention by 5-lipoxygenase inhibitor AA-861, and leukotriene receptor antagonist FPL-55712. AB - The extent of acute gastric lesions produced by intragastric administration of ethanol in mice paralleled gastric leukotriene (LT) C4 levels. Furthermore, an inverse dose-response relationship was observed between the extent of gastric lesions and the number of mast cells in the gastric mucosa. When mice were pretreated with the 5-lipoxygenase inhibitor, AA-861, both the extent of ethanol induced gastric lesions and the level of gastric LTC4 decreased dose-dependently. In contrast, when mice were pretreated with the LTC4 receptor antagonist, FPL 55712, the extent of ethanol-induced gastric lesions was depressed without significant reduction of gastric LTC4 level. These results indicate that both production of LTC4 and also subsequent binding of LTC4 to the receptors is important for the pathogenesis of gastric lesions and suggest that mast cell derived LTC4 plays a major role in the development of ethanol-induced gastric lesions. PMID- 1901046 TI - Cognitive impairment and disruptive behaviors among community-based elderly persons: implications for targeting long-term care. AB - This study estimates the prevalence of cognitive impairment and disruptive behaviors among functionally disabled elderly persons living in the community. The relationship between cognitive impairment, disruptive behaviors, and functional limitations is assessed. The impacts of adding cognitive and disruptive behavior eligibility requirements to commonly used functional disability criteria for long-term care benefits on the number of eligible persons are estimated. The number of eligible persons varies greatly under different criteria, depending on how cognitive and disruptive criteria are combined. PMID- 1901045 TI - The inhibitory effect of anti-tumor drugs on phosphatidylcholine synthesis and its reversal by geranylgeranylacetone in the isolated guinea pig gastric glands. AB - To clarify the mechanism by which the administration of anti-tumor drugs, antibiotics or hypoglycemic agents causes gastric mucosal injury, the effects of these drugs on phosphatidylcholine synthesis in isolated guinea pig gastric glands were examined in vitro. Anti-tumor drugs such as tegafur, cyclophosphamide, and mitomycin C decreased [3H]choline incorporation into phosphatidylcholine. Furthermore, tegafur at 0.4 mg/ml decreased [3H]choline incorporation in the glands that had been pulsed with [3H]choline incorporation, suggesting that tegafur exerts its effect by inhibiting late step of phosphatidylcholine synthesis in the stomach. On the other hand, cefaclor and glibenclamide had no effect on [3H]choline incorporation. Geranylgeranylacetone, an anti-ulcer drug partially restored tegafur-induced reduction of [3H]choline incorporation into phosphatidylcholine. These results suggest that the anti-tumor drug-induced gastric mucosal injury may be due to drug-induced decrease in phosphatidylcholine synthesis, which the restoration of phosphatidylcholine synthesis by geranylgeranylacetone may explain its anti-ulcer action on drug induced gastric mucosal lesions in vivo. PMID- 1901047 TI - Using ADLs to establish eligibility for long-term care among the cognitively impaired. AB - Using a database from the Oregon Medicaid program, we examined the differences in the potential insurance coverage of demented persons by using different formulations of ADL (activities of daily living) dependencies in which the definition of dependency did or did not include the need for supervision. For those with clear dementia, 81-88% of the persons with significant behavioral problems were correctly identified when a cut score of three or more ADLs was used; this percentage was even higher for two or more ADLs. This approach was not as effective in correctly discriminating those who had no behavioral problems. PMID- 1901048 TI - [Clinical applicability of intraperitoneal administration of nutrients and drugs]. PMID- 1901049 TI - [Clinical relevance of signal-intense foci in cerebral magnetic resonance tomography in neurofibromatosis]. AB - 37 patients with documented neurofibromatosis (15 children and 22 adults) had MR examination of the cerebrum. To determine the clinical relevance of signalintense foci in MRT EEG, BAEP and a neuropsychological test batteries was carried out. Our investigations showed that signalintense areas, which possibly represent dysplastic lesions, did not correlate with neurological deficits, epileptic seizures and cognitive disabilities. It remains unclear whether these lesions are of a potential malignancy. PMID- 1901050 TI - [Evaluation of the development of resistance as a factor for the limitation of therapeutic possibilities]. AB - From the microbiological point of view a variety of highly active compounds has contributed to improved efficacy of antibacterial chemotherapy during the last few decades. In some cases, however, resistance has increased due to different molecular mechanisms. Resistance to the new generation of broad-spectrum beta lactams is in the cases of TEM and SHV enzymes based upon the stepwise acquisition of point mutations within the structural gene. Multiresistance to aminoglycosides is caused by a combination of different genes coding for aminoglycoside modifying enzymes on transferable plasmids. Resistance to glycopeptides has recently been detected in enterococci and is due to a new mechanism of resistance. These substances have so far had unlimited activity against methicillin-resistant Staphylococcus aureus and have been widely used for treatment of pseudomembranous colitis. While all the three mechanisms of resistance mentioned above are transferable among different strains, no evidence exists so far for transferable resistance to 4-quinolones. However, for S. aureus and Pseudomonas aeruginosa an increase of resistance has been reported. The underlying mechanisms seem to be unchanged. The detection of global changes in the development of resistance and the discrimination of these changes from local events requires recording of statistically significant data obtained with approved methods and evaluation of the data with standardized international breakpoints. Consequently, the use of new agents should be controlled efficiently. PMID- 1901051 TI - The physiological significance of pulsatile LHRH secretion in man: gonadotrophin responses to physiological doses of pulsatile versus continuous LHRH administration. AB - This study tested whether pulsatile LHRH stimulation of the pituitary is required for normal gonadotrophin secretion in man. Four men with idiopathic hypogonadotrophic hypogonadism (IHH) and presumed endogenous LHRH deficiency were taken off all hormonal replacement for 5-6 weeks, then 5 micrograms LHRH was administered every 2 h for 1 week in order to prime pituitary gonadotrophin responsiveness. A physiological dose of LHRH (10 micrograms every 2 h) was then administered in both pulsatile and continuous regimens, in varying order, to each man. Pulsatile LHRH was capable of stimulating LH (as measured by bioassay) and FSH secretion, while continuous administration of LHRH was not. Serum LH, measured by RIA and bioassay, and FSH and free alpha-subunit levels, measured by RIA, increased significantly (P less than 0.05) over pretreatment levels during pulsatile LHRH administration. In contrast, bioactive LH and immunoactive FSH did not change significantly compared to pretreatment values during continuous infusion of the same total LHRH dose, although immunoactive LH and free alpha subunit levels did increase significantly (P less than 0.05). The ratio of LH bioactivity to immunoactivity was significantly lower during the continuous compared to pulsatile LHRH regimen (P less than 0.001). Similar serum LHRH levels were achieved during pulsatile and continuous infusions. Serum testosterone and oestradiol levels did not increase significantly from pretreatment levels during either regimen of LHRH administration. It is concluded that a pulsatile LHRH signal pattern is essential for normal pituitary gonadotrophin secretion in men with IHH. Continuous infusion of a physiological dose of LHRH, which produced serum LHRH levels which were indistinguishable from those found during pulsatile administration, failed to stimulate FSH or bioactive LH secretion. PMID- 1901052 TI - Low-temperature induction of Myxococcus xanthus developmental gene expression in wild-type and csgA suppressor cells. AB - The csgA gene encodes an extracellular protein that plays an essential role in the regulation of fruiting-body formation and sporulation of Myxococcus xanthus. The csgA suppressor allele soc-500 (formerly referred to as csp-500) was selected based on its ability to restore sporulation to csgA cells under developmental conditions at 32 degrees C. The soc-500 allele was subsequently found to induce sporulation of csgA+ or csgA cells simply by shifting the temperature of vegetatively growing cells to 15 degrees C. Low-temperature-induced sporulation of soc-500 strains occurred in the absence of two requirements for fruiting-body sporulation: low nutrient levels and a high temperature. Low temperature alone caused the expression of many developmentally regulated genes but did not support the development of wild-type cells. The soc-500 allele appears to activate genes involved with sensing nutritional stress. At low temperature on a nutritionally rich medium, soc-500 induced expression of the tps gene which is normally expressed following nutritional shiftdown. The soc-500 allele was cloned and integrated into the wild-type chromosome by site-specific recombination. It was dominant over the wild-type allele in merodiploids and is contained on a 3-kbp DraI-ClaI restriction fragment. The soc-500 transcriptional unit spans a 300-bp PstI-PstI restriction fragment, since deletion of the PstI restriction fragment inhibits both csgA suppression and low-temperature induction. These results suggest that the soc-500 mutation lies in a gene that is involved in nutrient sensing. PMID- 1901053 TI - A GTP-binding protein (Era) has an essential role in growth rate and cell cycle control in Escherichia coli. AB - Era is a membrane-associated GTP-binding protein which is essential for cell growth in Escherichia coli. In order to examine the physiological role of Era, strains in which Era was expressed at 40 degrees C but completely repressed at 27 degrees C were constructed. The growth of these strains was inhibited at the nonpermissive temperature, and cells became elongated. Under such conditions, no constrictions or septum formation could be detected by phase-contrast microscopy, and DNA segregation was apparently normal as revealed by fluorescence staining. These data demonstrate that Era has an essential function in cell growth rate control in liquid media and that depletion of Era blocks cell division either directly or indirectly. Thus, the role of GTP-binding proteins as important regulators of cell growth and division may be ubiquitous in nature. PMID- 1901054 TI - Use of alkaline phosphatase fusions to study protein secretion in Bacillus subtilis. AB - We have constructed a vector designed to facilitate the study of protein secretion in Bacillus subtilis. This vector is based on a translational fusion between the expression elements and signal sequence of Bacillus amyloliquefaciens alkaline protease and the mature coding sequence for Escherichia coli alkaline phosphatase (phoA). We show that export of alkaline phosphatase from B. subtilis depends on a functional signal sequence and that alkaline phosphatase activity depends upon secretion. The vector design facilitates the insertion of heterologous coding sequences between the signal and phoA to generate three-part translational fusions. Such phoA fusions are easily analyzed by monitoring alkaline phosphatase activity on agar plates or in culture supernatants or by immunological detection. Exploitation of this methodology, which has proven to be extremely useful in the study of protein secretion in E. coli, has a variety of applications for studying protein secretion in B. subtilis. PMID- 1901056 TI - Use of site-directed mutations in the individual Ca2(+)-binding sites of calmodulin to examine Ca2(+)-induced conformational changes. AB - Mutant versions of the calmodulin of Drosophila melanogaster have been prepared for use in the study of Ca2+ binding and Ca2(+)-induced conformational changes. In each mutant, a conserved glutamic acid residue indicated to play a critical role in Ca2+ binding has been mutated to glutamine in one of the Ca2(+)-binding sites. Thus a series of four proteins, each with an analogous mutation in one of the four binding sites, has been generated. Here the Ca2(+)-induced conformational changes in these proteins have been examined by use of the fluorescent hydrophobic reporter molecule, 9-anthroyl choline. These studies confirm earlier work which indicates that the carboxyl-terminal pair of Ca2(+) binding sites shows cooperative Ca2+ binding to produce a major conformational change in the protein. However, these studies provide evidence that the sites of the amino-terminal pair are more independent in their Ca2+ binding properties and contribute individually to the conformational changes associated with Ca2+ binding in the amino-terminal half of the protein. This work also indicates that mutation of either of the amino-terminal Ca2(+)-binding sites can influence the conformational change produced by Ca2+ binding to the carboxyl-terminal sites. PMID- 1901055 TI - DegS-DegU and ComP-ComA modulator-effector pairs control expression of the Bacillus subtilis pleiotropic regulatory gene degQ. AB - Production of a class of both secreted and intracellular degradative enzymes in Bacillus subtilis is regulated at the transcriptional level by a signal transduction pathway which includes the DegS-DegU two-component system and at least two additional regulatory genes, degQ and degR, encoding polypeptides of 46 and 60 amino acids, respectively. Expression of degQ was shown to be controlled by DegS-DegU. This expression is decreased in the presence of glucose and increased under any of the following conditions: growth with poor carbon sources, amino acid deprivation, phosphate starvation, and growth in the presence of decoyinine, a specific inhibitor of GMP synthetase. In addition, expression of degQ is shown to be positively regulated by the ComP-ComA two-component system. Separate targets for regulation of degQ gene expression by DegS-DegU and ComP ComA were located by deletion analysis between positions -393 and -186 and between positions -78 and -40, respectively. Regulation of degQ expression by amino acid deprivation was shown to be dependent upon ComA. Regulation by phosphate starvation, catabolite repression, and decoyinine was independent of the two-component systems and shown to involve sequences downstream from position -78. The ComP-ComA and DegS-DegU two-component systems seem to be closely related, sharing several target genes in common, such as late competence genes, as well as the degQ regulatory gene. Sequence analysis of the degQ region revealed the beginning of an open reading frame directly downstream from degQ. Disruption of this gene, designated comQ, suggests that it also controls expression of degQ and is required for development of genetic competence. PMID- 1901057 TI - Essential histidines of prostaglandin endoperoxide synthase. His-309 is involved in heme binding. AB - Prostaglandin endoperoxide (PGH) synthase has a single iron protoporphyrin IX which is required for both the cyclooxygenase and peroxidase activities of the enzyme. At room temperature, the heme iron is coordinated at the axial position by an imidazole, and about 20% of the heme iron is coordinated at the distal position by an imidazole. We have used site-directed mutagenesis to investigate which histidine residues are involved in PGH synthase catalysis and heme binding. Individual mutant cDNAs for ovine PGH synthases were prepared with amino acid substitutions at each of 13 conserved histidines. cos-1 cells were transfected with each of these cDNAs, and the cyclooxygenase and peroxidase activities of the resulting microsomal PGH synthases were measured. Mutant PGH synthases in which His-207, His-309, or His-388 was replaced with either glutamine or alanine lacked both activities. Gln-386 and Ala-386 PGH synthase mutants exhibited cyclooxygenase but not peroxidase activities. Other mutants exhibited both activities at varying levels. Because binding of heme renders native PGh synthase resistant to cleavage by trypsin, we examined the effects of heme on the relative sensitivities of native, Ala-204, Ala-207, Ala-309, Ala-386, and Ala-388 mutant PGH synthases to trypsin as a measure of the heme-protein interaction. The Ala 309 PGh synthase mutant was notably hypersensitive to tryptic cleavage, even in the presence of exogenous heme; in contrast, the native enzyme and the other alanine mutants exhibited similar, lower sensitivities toward trypsin and, except for the Ala-386 mutant, were partially protected from trypsin cleavage by heme. Preincubation of the native and each of the alanine mutant PGH synthases, including the Ala-309 mutant, with indomethacin protected the proteins from trypsin cleavage. Thus, all the mutant proteins retain sufficient three dimensional structure to bind cyclooxygenase inhibitors. Our results suggest that His-309 is one of the heme ligands, probably the axial ligand, of PGH synthase. Two other histidines, His-207 and His-388, are essential for both PGH synthase activities suggesting that either His-207 or His-388 can serve as the distal heme ligand; however, the trypsin cleavage measurements imply that neither His-207 nor His-388 is required for heme binding. This is consistent with the fact that only 20% of the distal coordination position of the heme iron of PGH synthase is occupied by an imidazole side chain. PMID- 1901058 TI - Inhibition of glycogen synthesis in Saccharomyces cerevisiae by the mating pheromone alpha-factor. AB - Treatment of the yeast Saccharomyces cerevisiae with the pheromone alpha-factor caused an inhibition of glycogen synthesis in MATa haploid cells but not in MAT alpha cells or MATa/MAT alpha diploid cells. The concentration of alpha-factor required for a half-maximal inhibition was comparable to that required for the induction of the FUS1 gene. Strains containing a disruption in ste2 or ste12 or temperature-sensitive mutations in ste4, ste7, or ste11 continued to divide and to accumulate glycogen in the presence of alpha-factor. In contrast, inhibition of glycogen occurred upon exposure to mating pheromone of far1 mutants which, under this condition, fail to arrest in G1 and continue to divide while simultaneously undergoing the transcriptional induction and morphological changes typical of mating cells. The inhibition of glycogen accumulation by alpha-factor persisted in a strain lacking glycogen phosphorylase (EC 2.4.1.1), which ruled out the participation of this enzyme in the pheromone response. Glycogen synthase (EC 2.4.1.11) from a cells treated with alpha-factor was found primarily in the glucose 6-phosphate-dependent (inactive) form whereas the total activity was unaltered. This indicates that the action of mating pheromone is mainly to inhibit the interconversion of the inactive glucose 6-phosphate-dependent form to the active glucose 6-phosphate-independent form of glycogen synthase without affecting the concentration of the enzyme. PMID- 1901059 TI - Early assembly proteins of the large ribosomal subunit of the thermophilic archaebacterium Sulfolobus. Identification and binding to heterologous rRNA species. AB - Studies of ribosome structure in thermophilic archaebacteria may provide valuable information on (i) the mechanisms involved in the stabilization of nucleic acid protein complexes at high temperatures and (ii) the degree of evolutionary conservation of the ribosomal components in the primary kingdoms of cell descent. In this work we investigate certain aspects of RNA/protein interaction within the large ribosomal subunits of the extremely thermophilic archaebacterium Sulfolobus solfataricus. The ribosomal proteins involved in the early reactions leading to in vitro particle assembly have been identified; it is shown that they can interact with the RNA in a temperature-independent fashion, forming a thermally stable "core" particle that can subsequently be converted into complete 50 S ribosomes. Among the protein components of the core particle, those capable of independently binding to 23 and 5 S RNA species have also been identified. Finally, we show that the early assembly proteins of Sulfolobus large ribosomal subunits are able to interact cooperatively with 23 S RNAs from other archaebacteria or from eubacteria, thereby suggesting that RNA/protein recognition sites are largely conserved within prokaryotic ribosomes. By contrast, no specific binding of the archaebacterial proteins to eukaryotic RNA could be demonstrated. PMID- 1901060 TI - Platelet-activating factor induces tyrosine phosphorylation in human neutrophils. AB - The addition of platelet-activating factor (PAF) to human neutrophils increases the levels of the tyrosine phosphorylation in several proteins. These proteins have molecular weights of 41 (pp41), 54 (pp54), 66 (pp66), 104 (pp104), and 116 (pp116) kDa. The effect of PAF was dose-dependent and could be seen at concentrations as low as 1 nM. The nonmetabolizable bioactive PAF analog, C-PAF, caused an increase in the level of phosphorylation of the same proteins in a time and dose-dependent manner. On the contrary, lyso-PAF, enantio-PAF, and L beta,gamma-dihexadecyl-alpha-lecithin failed to stimulate the phosphorylation of any of the aforementioned proteins. The response to PAF was prevented by the PAF antagonist BN-52021. The PAF-induced increases in tyrosine phosphorylation in pp66, pp116, and pp104 were selectively inhibited by pertussis toxin. In contrast, the level of pp41 phosphorylation remained unchanged after the pertussis toxin treatment. The calcium chelator EGTA significantly inhibited the PAF-produced phosphorylation of the pp41 protein. The intracellular calcium chelator 1,2-bis-(O-aminophenoxil)ethane-N,N,N',N'-tetraacetic acid (BAPTA) potentiated the PAF-enhanced levels of tyrosine phosphorylation on the pp41 protein. On the other hand, the PAF-induced phosphorylations of pp66, pp104, and pp116 were inhibited in BAPTA-treated cells. The calcium ionophore A23187 selectively potentiated the phosphorylation of the pp41 protein and reduced the phosphorylation in the pp54 protein. This phosphorylation was dependent on the extracellular calcium and was inhibited in toxin-treated cells. The results suggest that PAF is able to affect either directly or indirectly tyrosine kinase and/or phosphotyrosine phosphatase activities. The phosphorylation of the high and low molecular weight proteins are mediated by two different sets of kinases and/or phosphatases. PMID- 1901061 TI - Pseudomonas aeruginosa exoenzyme S requires a eukaryotic protein for ADP ribosyltransferase activity. AB - Pseudomonas aeruginosa exoenzyme S ADP-ribosylates several GTP-binding proteins of apparent Mr = 23,000-25,000. Exoenzyme S absolutely requires a soluble eukaryotic protein, which we have named FAS (Factor Activating exoenzyme S), in order to ADP-ribosylate all substrates. The rate of ADP-ribosylation of all exoenzyme S substrates increases linearly with time and with the FAS concentration. FAS is wide-spread in eukaryotes but appears to be absent from prokaryotes. We have estimated the molecular mass of the protein to be approximately 29,000 daltons and its pI to be 4.3-4.5. Several bacterial toxins share this sort of requirement for the presence of a eukaryotic protein for enzymic activity. In particular, FAS resembles ADP-ribosylation factor, a 21,000 dalton GTP-binding protein which performs an analogous function for cholera toxin. However, we can find no evidence that FAS binds GTP. In the presence of FAS, exoenzyme S ADP-ribosylates several proteins in lysates of P. aeruginosa. The requirement for a eukaryotic protein for enzymic activity, which is common to several bacterial toxins, may be a device to identify the eukaryotic environment and to ensure that the enzymes cannot function within and harm the toxin producing bacteria. PMID- 1901062 TI - Glucuronoxylan xylanohydrolase. A unique xylanase with the requirement for appendant glucuronosyl units. AB - A new category of beta-(1----4)-xylan xylanohydrolases that exhibit a specific capacity to hydrolyze glucuronoxylans was characterized using heteroxylans prepared from Vigna (Vigna angularis Ohwi et Ohashi cv. Takara) and maize (Zea mays L.) cell walls together with appropriate derivatives as substrates. Glucuronopyranosyl moieties, as side chains, were prerequisite for enzyme mediated hydrolysis of the beta-(1----4)-xylosyl linkages. The enzyme degraded glucuronoxylans derived from Vigna cell walls to yield a major oligomeric species (formula; see text) where Xyl represents xylose and GlcA represents glucuronic acid. The enzyme also degraded glucuronoarabinoxylans derived from maize cell walls to yield a major oligomeric species containing a single glucuronosyl side chain and a single unsubstituted beta 1----4Xyl pendant terminal. These results indicate that this xylanohydrolase recognizes glucuronosyl moieties inserted as monomeric side chains along the xylan backbone and mediates the hydrolysis of the beta-(1----4)-xylosyl linkage of the adjacent unsubstituted xylosyl residue in heteroxylans. This enzyme is the first xylanohydrolase identified that recognizes distinctly different sugars constituting side chains. We propose to designate this new enzyme as a glucuronoxylan xylanohydrolase to be abbreviated as glucuronoxylanase. Use of this unique enzyme demonstrated the presence of repeating units in heteroxylans in cell walls of higher plants. PMID- 1901063 TI - Enhancement of the actions of smg p21 GDP/GTP exchange protein by the protein kinase A-catalyzed phosphorylation of smg p21. AB - We have previously shown that cyclic AMP-dependent protein kinase (protein kinase A) phosphorylates smg p21A and -B, ras p21-like small GTP-binding proteins. In the present study, we investigated the function(s) of this phosphorylation by use of the smg p21B purified from human platelets. smg p21B bound to plasma membranes and the protein kinase A-catalyzed phosphorylation of smg p21B reduced this binding. Moreover, the phosphorylation of smg p21B enhanced the two actions of its specific GDP/GTP exchange protein, named GDP dissociation stimulator, when tested in a cell-free system: one is the action to stimulate the GDP/GTP exchange reaction of smg p21B, and the other is the action to inhibit the binding of smg p21B to membranes. Consistently, smg p21B was translocated from the membranes to the cytoplasm when it was phosphorylated by protein kinase A in intact platelets in response to prostaglandin E1 or dibutyryl cyclic AMP. The protein kinase A catalyzed phosphorylation of smg p21B affected neither its basal GDP/GTP exchange reaction, basal GTPase activity, nor the GTPase activity stimulated by its specific GTPase activating protein. On the other hand, we have recently clarified that the structure of the C-terminal region of the post-translationally processed human platelet smg p21B is Lys-Lys-Ser-Ser-all-trans-geranylgeranyl Cys181 methyl ester, and that this modification of the C-terminal region is essential for smg p21B to bind to membranes. We furthermore determined here that protein kinase A phosphorylated Ser179 in this C-terminal region of smg p21B. These results indicate that protein kinase A-catalyzed phosphorylation of smg p21B makes smg p21B sensitive to the actions of smg p21 GDP dissociation stimulator. PMID- 1901064 TI - Sequential mast cell infiltration and degranulation during experimental carcinogenesis. AB - Mast cell density, distribution, and ultrastructure were studied by light and electron microscopy in hamster buccal pouches undergoing chemically induced carcinogenesis. Epidermoid carcinomas in the pouches were induced by three topical applications per week of 0.5% 7,12-dimethylbenz[a]anthracene (DMBA) in oil using a brush. Four experimental, DMBA-treated and two normal, untreated hamsters were sacrificed after 8, 10, 12, 14, and 16 weeks. After 8 weeks of DMBA treatment, the epithelium showed the pathological signs of dysplasia and hyperkeratosis. In the dermis an increased number of mast cells were evident, some of which showed degranulation. A few mast cells had started to migrate upwards towards the dysplastic epithelium after 10 weeks of DMBA treatment. Rapid degranulation was also apparent in some mast cells. These processes of upward migration and degranulation continued progressively during the 12- and 14-week periods of DMBA application in correlation with the progression of the tumor. By 16 weeks of treatment with the carcinogen, more mast cells had migrated closer to the invasive carcinoma, and many had degranulated. In the connective tissue mast cells were fully packed with many granules, and some mast cells were in proximity to macrophages and eosinophils. Our observations demonstrate that there is a positive correlation between developing carcinomas and mast cell density. Mast cell migration towards the carcinoma and degranulation were also evident. PMID- 1901065 TI - Cytoplasmic lipid bodies of neutrophils: formation induced by cis-unsaturated fatty acids and mediated by protein kinase C. AB - Lipid bodies, nonmembrane-bound cytoplasmic inclusions, serve as repositories of esterified arachidonate and are increased in cells associated with inflammatory reactions. We have evaluated stimuli and mechanisms responsible for lipid body formation within human polymorphonuclear leukocytes (PMNs). Arachidonic acid and oleic acid stimulated dose-dependent formation of lipid bodies over 0.5-1 h. Other C20 and C18 fatty acids were less active and demonstrated rank orders as follows: cis-unsaturated fatty acids were much more active than trans-fatty acids, and activity diminished with decreasing numbers of double bonds. Lipid bodies elicited in vitro with cis-fatty acids were ultrastructurally identical to lipid bodies present in PMNs in vivo. Lipid body induction was not because of fatty acid-elicited oxidants or fatty acid-induced ATP depletion. Cis-fatty acid induced activation of protein kinase C (PKC) was involved in lipid body formation as evidenced by the capacity of other PKC activators, 1-oleoyl-2-acetyl-glycerol and two active phorbol esters, phorbol myristate acetate, and phorbol 12,13 dibutyrate, but not an inactive phorbol, to induce lipid body formation. The PKC inhibitor, 1-O-hexadecyl-2-O-methyl-glycerol, inhibited PMN lipid body formation induced by oleic and arachidonic acids and by 1-oleoyl-2-acetyl-glycerol and phorbol myristate acetate. Other PKC inhibitors (staurosporine, H-7) also inhibited lipid body formation. Formation of lipid bodies in PMNs is a specific cellular response, stimulated by cis-fatty acids and diglycerides and apparently mediated by PKC, which results in the mobilization and deposition of lipids within discrete, ultrastructurally defined cytoplasmic domains. PMID- 1901066 TI - The entry of Theileria parva sporozoites into bovine lymphocytes: evidence for MHC class I involvement. AB - We have examined the process of Theileria parva sporozoite entry into susceptible bovine lymphocytes and have begun to identify one of the possible molecular interactions involved in the process. The entry process involves a defined series of events and we have used a number of experimental procedures in combination with a method of quantitation to examine various aspects of this process. T. parva sporozoites are nonmotile organisms and the initial sporozoite-lymphocyte interaction is a chance event which can occur at 0-2 degrees C. All subsequent stages in the process are temperature dependent, require the participation of live intact sporozoites and host cells, and involve some cytochalasin-inhibitable rearrangement of the host cell surface membrane or cytoskeleton. Sporozoite entry can be inhibited by antibodies (mAbs) reactive with major histocompatibility complex (MHC) class I molecules (IL-A 19, IL-A 88) and with beta 2 microglobulin (B1G6), whereas mAbs reactive with MHC class II molecules (IL-A 21, J 11), and a common panleucocyte surface antigen, (IL-A 87; a bovine equivalent of CD 11a) have no effect. These results indicate that MHC class I molecules play a role in the process of T. parva sporozoite entry into bovine lymphocytes although as yet the precise role has not been determined. Once internalized within the lymphocyte, a process that takes less than 3 min at 37 degrees C, the sporozoite rapidly escapes from the encapsulating host cell membrane; a process which occurs concurrently with the discharge of the contents of the sporozoite rhoptries and microspheres. The intracytoplasmic parasite is covered by a layer of sporozoite derived fuzzy material to which host cell microtubules rapidly become associated. PMID- 1901067 TI - Interpretive criteria and quality control guidelines for Neisseria gonorrhoeae susceptibility test standardization for cefotetan. AB - Cefotetan was tested in a multilaboratory study to standardize susceptibility testing criteria and quality control guidelines for Neisseria gonorrhoeae. Cefotetan was most active against penicillinase-producing and penicillin susceptible strains (MIC for 50% of strains tested, 0.5 micrograms/ml) and was least active against the chromosomally resistant isolates (MIC for 50% of strains tested, 2 micrograms/ml). The recommended 30-micrograms disk cefotetan interpretive criteria were as follows: susceptible at greater than or equal to 26 mm (less than or equal to 2 micrograms/ml), intermediate at 20 to 25 mm (4 micrograms/ml), and resistant at less than or equal to 19 mm (greater than or equal to 8 micrograms/ml). Quality control guidelines for agar dilution and disk diffusion tests were established by using numerous GC agar lots, three cefotetan 30-micrograms disk lots, two quality control organisms, and a volume of tests consistent with National Committee for Clinical Laboratory Standards M23-T guidelines. PMID- 1901068 TI - Phenotypic conversion of Pseudomonas aeruginosa. PMID- 1901069 TI - Dopa reaction test in hair bulbs of fetuses and its application to the prenatal diagnosis of albinism. AB - No information is available on the amount of tyrosinase normally present in fetuses. A dopa reaction test in hair bulbs from the scalp of normal fetuses obtained after abortion showed that tyrosinase is present in fetuses as early as 17 weeks. Only faint activity was detected in skin specimens other than from the scalp. This assay can serve as a quick and reliable method for the prenatal diagnosis of tyrosinase-negative albinism. PMID- 1901070 TI - Short-term systemic recombinant interferon-gamma treatment is ineffective in recalcitrant condylomata acuminata. PMID- 1901072 TI - Comparison of the effects of streptokinase and tissue plasminogen activator on regional wall motion after first myocardial infarction: analysis by the centerline method with correction for area at risk. AB - In a trial of streptokinase versus recombinant tissue-type plasminogen activator (rt-PA) for a first myocardial infarction, 270 patients were randomized. Regional left ventricular function was assessed in 214 patients at 3 weeks. The infarct related artery was the left anterior descending artery in 78 patients, the right coronary artery in 122 and a dominant left circumflex artery in 14. Analysis was by the centerline method with a novel correction for the area of myocardium at risk, whereby the search region was determined by the anatomic distribution of the infarct-related artery. Infarct-artery patency at 3 weeks was 73% in the streptokinase group and 71% in the rt-PA group. Global left ventricular function did not differ between the two groups. Mean chord motion (+/- SD) in the most hypokinetic half of the defined search region was similar in the streptokinase and rt-PA groups (-2.4 +/- 1.5 versus -2.3 +/- 1.3, p = 0.63). There were no differences in hyperkinesia of the noninfarct zone. Compared with conventional centerline analysis, regional wall motion in the defined area at risk was significantly more abnormal. The two methods correlated strongly, however (r = 0.99, p less than 0.0001), and both methods produced similar overall results. Patients with a patent infarct-related artery and those with an occluded artery at the time of catheterization had similar levels of global function (ejection fraction 58 +/- 12% versus 57 +/- 12%, p = 0.58).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1901071 TI - Selective versus routine predischarge coronary arteriography after therapy with recombinant tissue-type plasminogen activator, heparin and aspirin for acute myocardial infarction. TIMI II Investigators. AB - To ascertain whether predischarge arteriography is beneficial in patients with acute myocardial infarction treated with recombinant tissue-type plasminogen activator (rt-PA), heparin and aspirin, the outcome of 197 patients in the Thrombolysis in Myocardial Infarction (TIMI) IIA study assigned to conservative management and routine predischarge coronary arteriography (routine catheterization group) was compared with the outcome of 1,461 patients from the TIMI IIB study assigned to conservative management without routine coronary arteriography unless ischemia recurred spontaneously or on predischarge exercise testing (selective catheterization group). The two groups were similar with regard to important baseline variables. During the initial hospital stay, coronary arteriography was performed in 93.9% of the routine catheterization group and 34.7% of the selective catheterization group (p less than 0.001), but the frequency of coronary revascularization (angioplasty or coronary artery bypass surgery) was similar in the two groups (24.4% versus 20.7%, p = NS). Coronary arteriograms showed a predominance of zero or one vessel disease (stenosis greater than or equal to 60%) in both groups (routine catheterization group 73.1%, selective catheterization group 61.3%). During the 1st year after infarction, rehospitalization for cardiac reasons and the interim performance of coronary arteriography were more common in the selective catheterization group (37.9% versus 27.6%, p = 0.007 and 28.6% versus 11.6%, p less than 0.001, respectively); however, the interim rates of death, nonfatal reinfarction and performance of coronary revascularization procedures were similar. At the end of 1 year, coronary arteriography had been performed one or more times in 98.9% of the routine catheterization group and 59.4% of the selective catheterization group (p less than 0.001), whereas death and nonfatal reinfarction had occurred in 10.2% versus 7.0% (p = 0.10) and 8.6% versus 9.0% (p = 0.87), respectively. Because the selective coronary arteriography policy exposes about 40% fewer patients to the small but finite risks and inconvenience of the procedure without compromising the 1 year survival or reinfarction rates, it seems to be an appropriate management strategy. PMID- 1901073 TI - Noninvasive detection of reperfusion in acute myocardial infarction based on plasma activity of creatine kinase MB subforms. AB - Successful thrombolytic therapy is associated with an accelerated release of creatine kinase (CK) MB from necrotic myocardium. With use of a previously validated assay, the plasma kinetics of the myocardial subform (MB2) and the plasma-modified subform (MB1) were determined in blood samples obtained from 56 patients with acute Q wave myocardial infarction: 33 patients who received thrombolytic therapy (group A) and 23 patients managed conservatively (group B). Plasma MB2 activity increased more rapidly in the group A patients, but there was substantial overlap with group B. Plasma MB1 activity did not differ significantly between the two groups. The MB2/MB1 ratio was significantly higher in group A patients than in group B patients between 2 and 10 h after the onset of infarction. Among group A patients, the ratio increased from 2.4 +/- 1.6 to 4.6 +/- 2.0 in the 1st h after therapy (p less than 0.001). The peak ratio was 6.3 +/- 2.5 in group A patients and 3.1 +/- 1.2 in group B patients. Twenty-seven of the 33 group A patients had a peak ratio greater than 3.8 versus 5 of the 23 group B patients (p less than 0.001). In seven group A patients, the ratio was greater than 3.8 before plasma CK MB activity was out of the normal range. Angiography was performed at 5.0 +/- 3.5 days in 39 patients. Eighteen (90%) of 20 patients with a patent infarct-related artery had a peak ratio greater than 3.8; 17 (89.5%) of 19 patients with an occluded infarct-related artery had a ratio less than 3.8 (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1901074 TI - Misoprostol and NSAID. PMID- 1901075 TI - Light chain deposition disease of the liver associated with AL-type amyloidosis and severe cholestasis. AB - A 67-year-old man with a 3-month history of jaundice presented with hepatomegaly. Laboratory studies revealed abnormal liver tests with raised bilirubin. Renal function was normal. Endoscopic retrograde cholangiopancreatography revealed normal extrahepatic bile ducts. Liver biopsy showed severe bilirubinostasis and a typical bile infarct. Laminar and globular deposits of PAS-positive diastase resistant non-congophilic material were observed in the sinusoidal walls. In addition, congophilic material was detected in the portal tracts. Immunohistochemistry revealed the presence of lambda-light chain deposits both in the sinusoids and in the portal tracts. Collagens type I and IV and fibronectin appeared markedly increased in the perisinusoidal space. On electron microscopy, the deposited material in the Disse spaces was mainly composed of fibrils indistinguishable from amyloid, admixed with small amounts of granular electron dense material. The similarities of light chain deposition disease and AL amyloidosis are discussed. PMID- 1901076 TI - Early thrombolytic treatment reduces analgesic requirement in patients with myocardial infarction. AB - The duration and amount of analgesics required were investigated in 67 patients with myocardial infarction treated with intravenous recombinant tissue-type plasminogen activator (rtPA) or placebo in a randomized double-blind trial. Infusion of rtPA (100 mg)/placebo was started within 5 h after the onset of symptoms, and the requirement for analgesics during the following 48 h was recorded. Sixty-seven per cent of the 30 rtPA-treated patients required analgesic treatment for less than 6 h, compared to 38% of the 37 patients in the placebo group (P = 0.04). During the study period, patients in the rtPA group used the equivalent of 5.3 mg (median value) intravenous morphine, which was significantly less than the 11.2 mg used in the placebo group (P = 0.04). In conclusion, the present study suggests that early thrombolysis with intravenous rtPA reduces the amount and duration of analgesic treatment required by patients with myocardial infarction. PMID- 1901077 TI - Central hypothyroidism due to isolated TRH deficiency in a depressive man. AB - A depressive man was evaluated for developing chronic fatigue and cold intolerance, in whom laboratory findings showed decreased thyroid hormone levels (T4, 2.7 micrograms dl-1; T3, 0.76 ng ml-1) with normal blood levels of TSH. A single bolus injection of TRH (500 micrograms) significantly stimulated prolactin secretion, but did not cause an increase in blood TSH levels (basal level, 1.2 microU ml-1 vs. 1.3 microU ml-1 30 min after injection). By contrast, TRH-induced TSH stimulation occurred after repeated injection of TRH for 4 consecutive days (basal level, 1.5 microU ml-1 vs. 5.6 microU ml-1 30 min after injection). Blood thyroid hormone concentrations were restored to normal levels after long-term administration of TRH. Other pituitary functions remained unchanged. A diagnosis of central hypothyroidism due to isolated TRH deficiency was made in this case, and the data presented here indicate that partial resistance of pituitary thyrotrophs to TRH may be associated with depression. PMID- 1901079 TI - Correlation between CD8 dependency and determinant density using peptide-induced, Ld-restricted cytotoxic T lymphocytes. AB - We have taken advantage of some unique properties of H-2Ld to investigate the determinant density requirements for cytotoxic T lymphocyte (CTL) priming versus effector function and to correlate the determinant density requirements with CD8 dependency. In a previous study (Lie, W.-R., N. B. Myers, J. Gorka, R. J. Rubocki, J. M. Connolly, and T. H. Hansen. 1990. Nature [Lond.]. 344:439), we demonstrated that culturing normal cells with peptides known to be restricted by H-2Ld led to a two- to fourfold increase in surface Ld expression. In the present study, we demonstrate the generation of Ld-restricted, peptide-specific in vitro primary CTL by culturing spleen cells with murine cytomegalovirus or tum- peptide at concentrations previously shown to result in maximum induction of Ld expression. Target cells can be sensitized for recognition by these CTL with lower dose of peptide than are required for the primary sensitization. This demonstrates differences in the determinant density requirements for priming versus effector function. The in vitro primary CTL generated with peptide can weakly lyse target cells that express the determinant endogenously, and CTL lines and clones capable of strong lysis of endogenous expressors are easily obtained. In both cases, target cells treated with exogenous peptide are lysed better than target cells expressing antigen endogenously. This suggested that there are differences in the determinant density of peptide-fed versus endogenous targets. This interpretation was substantiated when it was observed that the level of lysis of target cells expressing endogenous determinants correlated inversely with the amount of peptide required to sensitize targets for recognition by various tum- -specific CTL clones. Furthermore, simultaneous titration of both the peptide used to treat target cells and the antibody to CD8 revealed that the various CTL clones analyzed displayed widely disparate CD8 dependencies. In each case, the CD8 dependency correlated inversely with the determinant density requirement. Therefore, CD8 dependency of CTL is relative, but shows an absolute and quantitative correlation with their dependency on determinant density. These findings suggest that under physiologic conditions, where only low determinant densities are likely to be encountered, all CTL clones will show at least partial CD8 dependency. PMID- 1901078 TI - Differential tumor necrosis factor alpha expression by astrocytes from experimental allergic encephalomyelitis-susceptible and -resistant rat strains. AB - There is evidence that the cytokine tumor necrosis factor alpha (TNF-alpha) contributes to the pathogenesis of neurological autoimmune diseases such as multiple sclerosis (MS) and experimental allergic encephalomyelitis (EAE). TNF alpha exerts damaging effects on oligodendrocytes, the myelin-producing cell of the central nervous system (CNS), and myelin itself. We have recently demonstrated TNF-alpha expression from astrocytes induced by lipopolysaccharide (LPS), interferon gamma (IFN-gamma), and interleukin 1 beta (IL-1 beta). Astrocytes secrete TNF-alpha in response to LPS alone, and can be primed by IFN gamma to enhance LPS-induced TNF-alpha production. IFN-gamma and IL-1 beta, cytokines known to be present in the CNS during neurological disease states, do not induce TNF-alpha production alone, but act synergistically to stimulate astrocyte TNF-alpha expression. Inbred Lewis and Brown-Norway (BN) rats differ in genetic susceptibility to EAE, which is controlled in part by major histocompatibility complex (MHC) genes. We examined TNF-alpha gene expression by astrocytes derived from BN rats (resistant to EAE) and Lewis rats (highly susceptible). Astrocytes from BN rats express TNF-alpha mRNA and protein in response to LPS alone, yet IFN-gamma does not significantly enhance LPS-induced TNF-alpha expression, nor do they express appreciable TNF-alpha in response to the combined stimuli of IFN-gamma/IL-1 beta. In contrast, astrocytes from Lewis rats express low levels of TNF-alpha mRNA and protein in response to LPS, and are extremely responsive to the priming effect of IFN-gamma for subsequent TNF-alpha gene expression. Also, Lewis astrocytes produce TNF-alpha in response to IFN gamma/IL-1 beta. The differential TNF-alpha production by astrocytes from BN and Lewis strains is not due to the suppressive effect of prostaglandins, because the addition of indomethacin does not alter the differential pattern of TNF-alpha expression. Furthermore, Lewis and BN astrocytes produce another cytokine, IL-6, in response to LPS, IFN-gamma, and IL-1 beta in a comparable fashion. Peritoneal macrophages and neonatal microglia from Lewis and BN rats are responsive to both LPS and IFN-gamma priming signals for subsequent TNF-alpha production, suggesting that differential TNF-alpha expression by the astrocyte is cell type specific. Taken together, these results suggest that differential TNF-alpha gene expression in response to LPS and IFN-gamma is strain and cell specific, and reflects both transcriptional and post-transcriptional control mechanisms.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1901080 TI - Influence of dietary fat, vitamin E, ethoxyquin and indomethacin on the synthesis of prostaglandin E2 in brain regions of mice. AB - The regional brain synthesis of prostaglandin E2 (PGE2) of rats varies with age and dietary vitamin E. We investigated ex-vivo synthesis of PGE2 in brain regions of 24-mo-old male C57BL/6Nia mice. Mice were fed semipurified diets containing 1) 5% by weight of vitamin E-stripped corn oil, nonhydrogenated coconut oil or fish oil, or 2) 3.8% lard + 1.2% stripped corn oil (control), each supplemented with 30 or 500 mg of vitamin E per kg for 6 wk. In addition, two groups of mice were fed control diets containing 2500 mg of ethoxyquin/kg or 1 mg of indomethacin/(kg.day). Mice fed fish oil had lower (P less than 0.01) plasma alpha-tocopherol than those fed coconut oil. Vitamin E supplementation had no effect on the concentration of alpha-tocopherol in most brain regions. The rank order of PGE2 synthesis among all groups was cerebrum = cerebellum greater than midbrain greater than brainstem. Vitamin E supplementation tended to reduce brain PGE2 synthesis. Fat with 30 mg/kg of vitamin E in their diet. In the brainstem, fish oil significantly reduced PGE2 relative to mice fed corn oil. Ethoxyquin lowered plasma alpha-tocopherol by 42% and reduced the PGE2 synthesis in brain regions, and indomethacin reduced it by 50%. Thus, ethoxyquin and indomethacin significantly reduced the brain's regional capacity for PGE2 synthesis, whereas vitamin E was not effective for the period tested. The reduction of PGE2 synthesis in the brain with fish oil feeding in this study was not as notable as reported for other tissues unless combined with high-dose vitamin E supplementation. PMID- 1901081 TI - Neonatal screening for sickle cell disease: a cost-effectiveness analysis. AB - PURPOSE: To determine the cost-effectiveness of screening newborn infants for sickle cell disease. DESIGN: We developed a decision model that examined two strategies: (1) screening neonates and administering penicillin to infants found to have sickle cell disease in the hope of preventing pneumococcal sepsis, and (2) not screening but administering penicillin to infants after symptoms of sickle cell disease develop. The model calculates the cost-effectiveness of these strategies during the first 3 years of life. We applied the model to three prototypic populations of neonates--black, nonblack with a relatively high prevalence of hemoglobin S genes, and nonblack with a low prevalence of hemoglobin S genes. DATA IDENTIFICATION: We obtained from the published literature the effectiveness and risk of penicillin prophylaxis, the risk of pneumococcal sepsis, and the probability that in infants not screened the development of symptoms would lead to the discovery of sickle cell disease within the first 3 years of life; we used the published literature and the Hardy Weinberg law to determine the prevalence of sickle cell disease. We used actual variable costs of screening, antibiotic prophylaxis, and hospitalization for pneumococcal sepsis or anaphylaxis. RESULTS: Screening and then treating affected black infants costs only $3100 more per life saved than not screening. Screening nonblack populations with a high prevalence of hemoglobin S genes would cost $1.4 million per life saved, and screening low prevalence populations would cost $450 billion per life saved. CONCLUSIONS: Screening black infants is very worthwhile, but screening populations in which the hemoglobin S gene is rare is unjustified. PMID- 1901082 TI - Use of intravenously administered immune globulin in newborn infants: prophylaxis, treatment, both, or neither? PMID- 1901083 TI - Effect on neutrophil kinetics and serum opsonic capacity of intravenous administration of immune globulin to neonates with clinical signs of early-onset sepsis. AB - This study was designed to test the hypothesis that administration of immune globulin to human neonates with early-onset bacterial sepsis would (1) facilitate neutrophil egress from the marrow, (2) improve serum opsonic capacity, and (3) facilitate recovery from the infectious illness. Twenty-two newborn infants with clinical signs of early-onset sepsis were given an intravenous infusion of either 750 mg of immune globulin (IVIG) per kilogram of body weight or the same volume of a vehicle control (albumin). All 22 infants survived, but significant hematologic, immunologic, and respiratory differences were observed after the IVIG and not after the control infusion. Eleven of the patients had neutropenia; 24 hours after the infusions, the neutropenia had resolved in all six IVIG recipients but persisted in all five control recipients (p less than 0.001). Ten patients had I/T neutrophil ratios (a measure of immature neutrophils to total neutrophils on the leukocyte differential count) of less than 0.2. One hour after completion of the infusions, all five IVIG recipients had elevated I/T ratios (mean +/- SEM:0.10 +/- 0.05 before vs 0.43 +/- 0.03 after infusion; p less than 0.001), suggesting a prompt release of neutrophils from the marrow neutrophil storage pool into the circulation; no increase in the I/T ratio was observed in the control recipients. Six hours after the IVIG infusions, the ratio of arterial oxygen tension to fraction of inspired oxygen increased; no increase was observed after control infusions. Serum concentrations of IgG, IgG1, IgG2, IgG3, IgG4, and total hemolytic complement and the capacity of serum to support opsonophagocytosis of type II and type III group B streptococci increased markedly in the IVIG recipients but not in the control subjects. We conclude that administration of 750 mg IVIG per kilogram to neonates with clinical signs of early-onset sepsis was associated with immunologic, hematologic, and physiologic improvement. PMID- 1901084 TI - Treatment with intravenously administered gamma globulin of chronic relapsing colitis induced by Clostridium difficile toxin. AB - We tested the hypothesis that children with chronic relapsing colitis induced by Clostridium difficile toxin have defective antibody responses to C. difficile toxins as a cause of their underlying illness. Six such children were tested for serum IgG and IgA antibody to C. difficile toxin A. These six children had lower IgG anti-toxin A levels than 24 healthy children (p = 0.026) and 18 healthy adults (p = 0.0008). Five patients treated with 400 mg intravenously administered gamma-globulin per kilogram every 3 weeks had significant increases in IgG (p = 0.01) but not IgA anti-toxin A (p = 0.406) levels, and all five had clinical resolution of their gastrointestinal symptoms as well as clearing of C. difficile cytotoxin B from their stools. These observations suggest that a deficiency of IgG anti-toxin A may predispose children to the development of chronic relapsing C. difficile-induced colitis. In such cases, intravenous gamma-globulin therapy may be effective in producing clinical remission. PMID- 1901085 TI - Childhood cyanotic breath-holding spells and cardiorespiratory control. PMID- 1901086 TI - Total organic carbon measurement as a substitute for the USP oxidizable substances test. AB - The insensitivity and variability of response of the USP Oxidizable Substances Test for waters are investigated. Instrumental measurement of Total Organic Carbon (TOC) is described, and the method is compared with the Oxidizable Substances Test. Pharmaceutical factory measurements of TOC in various water systems are discussed. PMID- 1901087 TI - Placental MHC class I antigen expression is induced in mice following in vivo treatment with recombinant interferon-gamma. AB - Allogeneically pregnant mice (NFR/N (Swiss-derived) H2q x 57/B1 H2b) were injected daily from day 11 to 18 of gestation with recombinant rat interferon gamma (IFN-gamma) and the effects on placental MHC antigen expression were evaluated by immunohistochemistry. The results demonstrated that a daily dose of 200,000 U/mouse induces a significant increase in placental MHC class I expression in the decidua and the basal zone spongiotrophoblast as well as the fetal mesenchyme, while the labyrinthine trophoblast was almost completely MHC negative. No significant induction of MHC class II antigen expression was observed in the placental tissue, with the exception of a few scattered cells. The MHC class II-inducing efficiency of the treatment protocol used was ascertained by staining maternal skin (ear), which proved to contain considerably elevated numbers of MHC class II-positive cells (mainly keratinocytes). The IFN gamma treated group showed a higher incidence of fetal resorptions than the corresponding controls, but this was probably due to a non-specific toxic effect of the treatment as none of the sera analysed contained detectable amounts of anti-paternal antibodies, no infiltrating lymphocytes were detectable on histological examination of placental sections, and most of the IFN-gamma treated animals successfully completed their pregnancy. PMID- 1901088 TI - Factor VIII procoagulant: a marker of fibrinoid necrosis in normal term human placentae. AB - Factor VIII procoagulant (FVIIIPC) is a plasma glycoprotein cofactor for activated factor IX that activates factor X in prothrombin convertase and results in fibrin deposition. We have studied 50 normal term placentae for the presence of FVIIIPC, and found it in granular deposits almost exclusively in areas of fibrinoid necrosis. This observation was made in all fibrinoid areas. These deposits were associated with specific factors of the coagulation, anticoagulation and fibrinolytic pathways. These findings suggest coagulation and fibrinolysis are activated in areas of fibrinoid necrosis and indicate FVIIIPC is a marker of these areas. PMID- 1901089 TI - Ovulation induction with gonadotropins in women with polycystic ovary disease. AB - Seventy-two infertile women with polycystic ovary disease (PCOD) and clomiphene citrate treatment failure underwent 220 human menopausal gonadotropin (hMG) and human chorionic gonadotropin (hCG) treatment cycles for ovulation induction over a period of 19 months. Forty-two patients ovulated but failed to conceive on clomiphene, and the remaining 30 failed to ovulate on clomiphene. Monitoring of treatment consisted of serum 17 beta-estradiol (E2) levels and ultrasonic assessment of follicular growth. Treatment was withheld whenever the E2 levels exceeded 1,500 pg/mL and/or when more than two follicles greater than or equal to 17 mm in diameter each were encountered on ultrasonography. Twenty-nine patients conceived (40.2%), and 23 delivered viable infants. Twenty-three of the 29 pregnancies were achieved in the 42 patients who ovulated on clomiphene, while only 6 pregnancies resulted in the 32 anovulatory patients on clomiphene. Six patients (20.6%) aborted in the first trimester. Multiple pregnancies consisted of only two sets of twins (6.9%). There were only two cases of mild hyperstimulation (2.7%) and no severe hyperstimulation. Because of the low occurrence of multiple pregnancies and hyperstimulation and the reasonable success rate, all PCOD patients should be started on this protocol. PMID- 1901090 TI - Role of organic osmolytes in adaptation of renal cells to high osmolality. AB - Kidney cells accumulate organic osmolytes in order to protect themselves from the high concentrations of NaCl and urea in the blood and interstitial fluid of the renal medulla. The renal medullary organic osmolytes are sorbitol, inositol, betaine and GPC. The concentrations of these solutes in renal medullary NaCl and urea concentration, as summarized in Fig. 8 (the putative controlled steps are highlighted). Sorbitol accumulates by synthesis from glucose, catalyzed by aldose reductase. Hypertonicity increases the transcription of the gene that encodes this enzyme. GPC is synthesized from choline, and the amount retained apparently may be controlled by the activity of GPC diesterase, an enzyme that catabolizes GPC. Inositol and betaine are taken up from the medium by sodium-dependent transport, and this transport is increased by hypertonicity. Control of these processes is slow (hours to days), but a decrease in tonicity causes a transient, rapid efflux of the solutes, which prevents the cells from becoming overly distended. Similar strategies are used by all types of cells, including bacteria and those in plants and animals, that can adapt to hyperosmotic stress. PMID- 1901091 TI - Uniformity in the nonsynonymous substitution rates of embryonic beta-globin genes of several vertebrate species. AB - The nucleotide substitution rate in structural portions of the embryonic beta globin genes of placental mammals is lower than that for the adult beta-globin genes. This difference occurs entirely within the class of substitutions that result in nonsynonymous (replacement) differences between these genes, and therefore represents a constraint on the structure of the mammalian embryonic beta-globin proteins relative to the adult proteins (Shapiro et al. 1983; Hardison 1984). A similar effect has also been observed in marsupial mammals (Koop and Goodman 1988). In an effort to determine whether the observed rates are evidence of a uniform degree of selective constraint on the embryonic beta-globin genes, analyses were performed that compared replacement substitution rates. The analyses reveal that embryonic beta-globin genes appear to have been fixing replacement substitutions at nearly the same average rate not only in placental and marsupial mammals but in avian and amphibian species as well. In contrast, the adult beta-globin genes from these organisms appear to have a more variable rate of replacement substitution with an especially low rate for birds. In the chicken (Gallus gallus), the adult beta-globin gene replacement substitution rate appears to be lower than the embryonic replacement substitution rate. PMID- 1901092 TI - Evolution of the cytochrome b gene of mammals. AB - With the polymerase chain reaction (PCR) and versatile primers that amplify the whole cytochrome b gene (approximately 1140 bp), we obtained 17 complete gene sequences representing three orders of hoofed mammals (ungulates) and dolphins (cetaceans). The fossil record of some ungulate lineages allowed estimation of the evolutionary rates for various components of the cytochrome b DNA and amino acid sequences. The relative rates of substitution at first, second, and third positions within codons are in the ratio 10 to 1 to at least 33. For deep divergences (greater than 5 million years) it appears that both replacements and silent transversions in this mitochondrial gene can be used for phylogenetic inference. Phylogenetic findings include the association of (1) cetaceans, artiodactyls, and perissodactyls to the exclusion of elephants and humans, (2) pronghorn and fallow deer to the exclusion of bovids (i.e., cow, sheep, and goat), (3) sheep and goat to the exclusion of other pecorans (i.e., cow, giraffe, deer, and pronghorn), and (4) advanced ruminants to the exclusion of the chevrotain and other artiodactyls. Comparisons of these cytochrome b sequences support current structure-function models for this membrane-spanning protein. That part of the outer surface which includes the Qo redox center is more constrained than the remainder of the molecule, namely, the transmembrane segments and the surface that protrudes into the mitochondrial matrix. Many of the amino acid replacements within the transmembrane segments are exchanges between hydrophobic residues (especially leucine, isoleucine, and valine). Replacement changes at first and second positions of codons approximate a negative binomial distribution, similar to other protein-coding sequences. At four-fold degenerate positions of codons, the nucleotide substitutions approximate a Poisson distribution, implying that the underlying mutational spectrum is random with respect to position. PMID- 1901094 TI - The evolution of plasmodial stage-specific rRNA genes is dominated by gene conversion. AB - Plasmodium species exhibit the unprecedented situation of distinct, stage specific rRNA sequences. We present an analysis of two pairs of sequences of the small rRNA subunit (Plasmodium falciparum and Plasmodium berghei) and show that these genes do not evolve independently and that in fact their evolution is dominated by gene conversion. This analysis also shows that no extensive stage specific sequences are conserved in the two species, thus rendering unlikely that the existence of stage-specific rRNA genes results from a requirement for distinct rRNA types. PMID- 1901093 TI - The evolutionary position of the rhodophyte Porphyra umbilicalis and the basidiomycete Leucosporidium scottii among other eukaryotes as deduced from complete sequences of small ribosomal subunit RNA. AB - The complete small ribosomal subunit RNA (srRNA) sequence was determined for the red alga Porphyra umbilicalis and the basidiomycete Leucosporidium scottii, representing two taxa for which no srRNA sequences were hitherto known. These sequences were aligned with other published complete srRNA sequences of 58 eukaryotes. Evolutionary trees were reconstructed by a matrix optimization method from a dissimilarity matrix based on sections of the alignment that correspond to structurally conservative areas of the molecule that can be aligned unambiguously. The overall topology of the eukaryotic tree thus constructed is as follows: first there is a succession of early diverging branches, leading to a diplomonad, a microsporidian, a euglenoid plus kinetoplastids, an amoeba, and slime molds. Later, a nearly simultaneous radiation seems to occur into a number of taxa comprising the metazoa, the red alga, the sporozoa, the higher fungi, the ciliates, the green plants, plus some other less numerous groups. Because the red alga diverges late in the evolutionary tree, it does not seem to represent a very primitive organism as proposed on the basis of morphological and 5S rRNA sequence data. Asco- and basidiomycetes do not share a common ancestor in our tree as is generally accepted on the basis of conventional criteria. In contrast, when all alignment positions, rather than the more conservative ones, are used to construct the evolutionary tree, higher fungi do form a monophyletic cluster. The hypothesis that higher fungi and red algae might have shared a common origin has been put forward. Although the red alga and fungi seem to diverge at nearly the same time, no such relationship can be detected. The newly determined sequences can be fitted into a secondary structure model for srRNA, which is now relatively well established with the exception of uncertainties in a number of eukaryote specific expansion areas. A specific structural model featuring a pseudoknot is proposed for one of these areas. PMID- 1901095 TI - cDNA and amino acid sequences of rainbow trout (Oncorhynchus mykiss) lysozymes and their implications for the evolution of lysozyme and lactalbumin. AB - The complete 129-amino-acid sequences of two rainbow trout lysozymes (I and II) isolated from kidney were established using protein chemistry microtechniques. The two sequences differ only at position 86, I having aspartic acid and II having alanine. A cDNA clone coding for rainbow trout lysozyme was isolated from a cDNA library made from liver mRNA. Sequencing of the cloned cDNA insert, which was 1 kb in length, revealed a 432-bp open reading frame encoding an amino terminal peptide of 15 amino acids and a mature enzyme of 129 amino acids identical in sequence to II. Forms I and II from kidney and liver were also analyzed using enzymatic amplification via PCR and direct sequencing; both organs contain mRNA encoding the two lysozymes. Evolutionary trees relating DNA sequences coding for lysozymes c and alpha-lactalbumins provide evidence that the gene duplication giving rise to conventional vertebrate lysozymes c and to lactalbumin preceded the divergence of fishes and tetrapods about 400 Myr ago. Evolutionary analysis also suggests that amino acid replacements may have accumulated more slowly on the lineage leading to fish lysozyme than on those leading to mammal and bird lysozymes. PMID- 1901096 TI - Reducing high blood cholesterol levels with drugs. PMID- 1901097 TI - A tribute to Harry M. Shizgal, M.D. JPEN editor-in-chief, 1981-90. PMID- 1901098 TI - Total parenteral nutrition-induced steatosis: reversal by parenteral lipid infusion. AB - Prolonged use of total parenteral nutrition (TPN) may be associated with hepatic complications, primarily steatosis and cholestasis. A case is reported of an 18 year-old woman with chronic idiopathic intestinal pseudo-obstruction syndrome who was on prolonged home parenteral nutrition without lipid supplementation and developed steatosis. This finding was reversed by addition of lipid emulsion, at a dose of 0.5 g/kg/day, to the parenteral nutrition solution. The lack of lipid supplementation as a possible cause of steatosis, as well as other mechanisms of liver steatosis associated with TPN, are discussed. PMID- 1901099 TI - Severe lactic acidosis related to acute thiamine deficiency. AB - The authors report a case of severe lactic acidosis in a 3-year-old boy, after 20 days of total parenteral nutrition without vitamin supplementation. This child with acute lymphoblastic leukemia underwent a period of severe refractory lactic acidosis (pH between 6.81 and 7.00 and a serum lactate level up to 38 mmol/liter) leading to cardiac arrest. After the initial resuscitation and the subsequent treatment of shock and vitamin K deficiency, acute peritoneal dialysis was instituted to correct the severe lactic acidosis. Initial low plasma thiamine levels confirmed the diagnosis of thiamine deficiency. An associated transient pancreatic dysfunction was also noted. The patient's overall course with thiamine replacement therapy led to a complete recovery within 5 days and no sequelae were noted after 12 months. PMID- 1901100 TI - Cardiac tamponade and hydrothorax as complications of central venous parenteral nutrition in infants. AB - The recent use of soft catheters made of silastic polymeric silicone or polyurethane has decreased the incidence of perforation of great veins or right sided heart chambers but has not eliminated it as had been hoped. Two premature infants who presented with cardiac tamponade more than 24 hr after the insertion of a 23-gauge silastic catheter for total parenteral nutrition (TPN) administration are described. In one infant, bilateral hydrothorax preceded the occurrence of cardiac tamponade. Osmotic injury to great vessels and/or myocardium seems to be the common mechanism but which these complications of intraluminal catheters are produced. Review of the pediatric literature revealed a proportion of low birth weight infants among the reported cases. Despite a prohibitively high mortality rate, early recognition can prevent a fatal outcome. PMID- 1901101 TI - Intravenous fluids in neonates. PMID- 1901102 TI - Comparison of acute and chronic protein-energy malnutrition on host antitumor immune mechanisms. AB - Protein-calorie malnutrition (PCM) is prevalent in cancer patients. However, the effect of PCM on anti-tumor immunity is unclear and critically important in an era of improving results with adoptive immunotherapy. This study examined the effect of short- and long-term PCM on tumor-specific and natural immune effector mechanisms in a murine neuroblastoma (C1300 NRB) model. A/J mice received an isocaloric 2.5% or 24% casein diet for 3 or 8 weeks before inoculation with tumor. Three weeks later lymphocytes from tumor-bearing mice were harvested for determination of cytotoxic T lymphocyte (CTL) generation and natural killer (NK) cell cytotoxicity. Both 3 and 8 weeks of PCM significantly reduced mean total body weight by 25% (p less than 0.001) and 41% (p less than 0.001), respectively, compared with regularly nourished mice. Short-term PCM did not inhibit CTL or NK cytotoxicity, whereas long-term PCM significantly diminished CTL generation (p less than 0.001) but preserved NK cytotoxic function. These results indicate that CTL development against autologous tumor, in contrast to basal NK function, is dependent on host nutritional status. Mean tumor growth, determined by tumor weight to carcass-weight ratio, was unchanged for both short- and long-term protein-energy deprived groups compared with results in regularly nourished mice. These findings suggest that NK function is the predominant effector mechanism inhibiting C1300 NRB growth and that NK tumoricidal capacity is preserved during PCM. PMID- 1901103 TI - Metabolic and immune effect of vitamin E supplementation after burn. AB - The effect of dietary vitamin E supplementation was studied in burned guinea pigs. Forty-four guinea pigs bearing a catheter gastrostomy received a 30% total body surface area full thickness flame burn and were given identical enteral diets (175 kcal/kg/day) except for the amount of vitamin E. Groups 1, 2, 3, and 4 received 0, 4 mg/kg/day (approximately equivalent to guinea pig's RDA) 20 or 100 mg/kg/day of vitamin E respectively. After 14 days of enteral feeding, there were no significant differences between groups in the body weights and the weights of carcass, gastrocnemius muscle, liver, and spleen. Resting metabolic expenditure on PBD 3, 6, 9, and 12 was similar in all groups. No statistical differences were seen in ear-thickness response to 2,4-dinitrofluorobenzene and lymphocytic proliferative responses to phytohemagglutinin. However, mucosal weight and protein content in group 1 were significantly less compared to groups 2 and 4 (p less than 0.05). Anemia was also significantly greater in group 1. Histologic examination of the intestinal wall, however, did not yield any physical differences associated with the addition of vitamin E to the diet. This study suggests that vitamin E supplementation in diets of burned animals may have a beneficial effect on maintenance of intestinal mucosa and erythrocyte counts over a wide-dose range. PMID- 1901104 TI - Thermogenesis from intravenous medium-chain triglycerides. AB - Eighteen hospitalized patients dependent on total parenteral nutrition (TPN) were randomly enrolled into a prospective study comparing intravenous long-chain triglycerides (LCT) with a physical mixture of 75% medium-chain triglycerides (MCT) and 25% LCT. The TPN was given continuously as amino acids and glucose over 5 days with the respective lipid emulsion given intermittently during each day for 10 hr. Indirect calorimetry was measured on each patient before the lipid emulsion was administered in the morning and again 10 hr later near the end of the lipid infusion, on days 1, 3, and 5. Resting energy expenditure, VO2, VCO2, and calculated fat oxidation were shown to increase during MCT infusion but not during LCT administration, (resting energy expenditure 899 +/- 37 to 1085 +/- 40, compared with 978 +/- 23 to 976 +/- 39, kcal/m2 body surface area [BSA]/day, respectively, p less than 0.0002; VO2: 129.9 +/- 5.2 to 157.2 +/- 5.9, compared with 140.9 +/- 3.6 to 141.2 +/- 5.9 ml O2/min/m2 BSA, respectively, p less than 0.0005; and VCO2: 110.7 +/- 4.4 to 127.5 +/- 4.3, compared with 118.3 +/- 2.8 to 118.0 +/- 5.3, ml CO2/min/m2 BSA, respectively, p less than 0.0076; calculated fat oxidation 10.7 +/- 1.5 to 19.3 +/- 2.4, compared with 20.0 +/- 2.7 to 20.0 +/ 3.6, kcal/m2 BSA/hr, respectively, p less than 0.014). Respiratory quotient tended to fall with lipid infusion but did not change statistically. Body temperatures were unaltered by either fat infusion. It is concluded that TPN consisting of MCT causes an increased thermogenesis, most likely through increased fat oxidation, reflective of MCT's property as an obligate fuel. The increased thermogenesis occurs without an increase in body temperature. PMID- 1901105 TI - Triacetin: a potential parenteral nutrient. AB - Triacetin, the water-soluble triglyceride of acetate, was infused in mongrel dogs at isocaloric (N = 6) or hypercaloric (approximately 1.5 REE, N = 7) rates in mongrel dogs for 3 hr. Ketone body and glucose production rates were quantified with [13C2] acetoacetate and [3H]glucose, respectively. Four additional animals were infused with glycerol to serve as controls for the hypercaloric triacetin infusion. Energy expenditure was determined in the isocaloric experiments. RESULTS: no evidence of acute toxicity was observed during triacetin infusion at either rate. Plasma acetate concentrations increased from basal levels to approximately 1 and approximately 13 mmol/liter in the isocaloric and hypercaloric experiments, respectively. Plasma lactate and pyruvate concentrations decreased dramatically after 30 min of both isocaloric and hypercaloric triacetin infusions. Glucose production rates did not increase in either group, but glucose clearance decreased significantly in both groups (p less than 0.05) over the last hour of triacetin infusion. Plasma ketone body concentrations increased from 1.4 to 3.5 and 1.8 to 13.5 mumol/kg.min, respectively, during isocaloric and hypercaloric triacetin infusion. Resting energy expenditure increased from 3.0 +/- 0.3 to 4.0 +/- 0.5 kcal/kg.hr during isocaloric triacetin infusion (p less than 0.05). These studies indicate that triacetin can be administered to dogs at high rates without overt toxicity. The decrease in glucose clearance may represent competition between carbohydrate (glucose) and lipid (acetate). Triacetin infusion resulted in significant increases in ketone body production and concentration. These preliminary data indicate that triacetin may have a future role as a parenteral nutrient, and that further studies of its use are warranted. PMID- 1901106 TI - Metabolic and neurologic effects of an intravenous medium-chain triglyceride emulsion. AB - These studies were undertaken to investigate the relationship between medium chain fatty acid availability, medium-chain fatty acid oxidation, and central nervous system toxicity during infusion of medium-chain triglycerides in dogs. Six dogs received a sequential, stepwise infusion of trioctanoin at three different rates for 80 min each, providing calories below and equal to resting energy expenditure in the species. Ketone body production rates (using a 14C beta hydroxybutyrate tracer) and plasma concentrations of lactate and octanoate were monitored. Three animals were infused with saline to serve as controls. Blood brain barrier integrity was assessed with Evans blue dye, and brain samples were taken at the end of the study to quantify brain water. Three animals were studied under anesthesia to obtain good quality EEG and intracranial pressure measurements. Results were (1) plasma octanoate increased to 0.37 +/- 0.13, 0.78 +/- 0.2, and 1.44 +/- 0.41 mmol/liter during the three infusion intervals; (2) emesis, somnolence, and coma were observed at the two highest trioctanoin rates; (3) ketone body concentrations and production increased from 102 +/- 15 to 859 +/ 54 mumol/liter and 3.6 +/- 0.43 to 18.5 +/- 1.7 mumol/kg/min, respectively, at the highest trioctanoin infusion rate; and (4) plasma lactate also increased from 1.3 +/- 0.1 to 4.3 +/- 0.9 mmol/liter at the highest infusion rate. EEG changes were also observed, consisting of high amplitude slowing and reduction in amplitude of faster components. There was no extravasation of Evans blue dye, nor change in brain water or intracranial pressure. The conclusion--medium-chain triglycerides have significant dose-related central nervous system toxicity in dogs. Therefore, caution should be exercised in clinical studies with MCTs, including careful measurement of medium-chain fatty acid concentrations. PMID- 1901107 TI - Effect of enteral diets on whole body and gut growth in unstressed rats. AB - The composition of enteral feeding formulas may have different effects on total body and gut growth. We studied the growth effects in rats of a complex solid fiber-based diet (Prolab Rodent Diet) with that of three isocaloric and isonitrogenous commercially available liquid feeding formulas which differ in their type of protein (Osmolite HN, an intact protein formula; Reabilan HN, a peptide formula; and Vivonex-TEN, an amino acid formula). Total body weight gain was greatest with the rodent diet (93 +/- 2 g/10 days), followed by the peptide diet (72 +/- 5 g/10 days) and intact protein diet (58 +/- 8 g/10 days). Weight gain was significantly lower on the amino acid diet (43 +/- 7 g/10 days). Proximal and mid gut mass was comparable with all four diets, but distal gut mass was significantly lower with the amino acid diet. Somatomedin C levels on the rodent diet (13.3 +/- 1.8 nM), and the peptide diet (14.0 +/- 3.3 nM) were significantly higher than somatomedin C levels on the amino acid diet (8.0 +/- 1.0 nM). Somatomedin C levels on the intact protein diet (9.6 +/- 1.4 nM) were intermediate between the rodent diet and amino acid diet. We conclude that growth effects vary with different enteral diets (unrelated to total calories and protein) and may result from differences in the generation of tissue growth factors. PMID- 1901108 TI - Liver function tests in patients receiving parenteral nutrition. AB - A 5-year prospective study was performed to monitor liver function tests (LFTs) in patients receiving total parenteral nutrition (TPN). A gradual and progressive rise was seen in the plasma concentration of bilirubin, aspartate transaminase, and alkaline phosphatase. The rate of rise was not increased in patients with LFT abnormalities before the start of TPN. Half of the patients had an episode of sepsis during TPN, but overall abnormal LFTs did not appear more common in these patients than in those without obvious sepsis. Patients with malignant disease, those requiring long-term TPN, and those requiring a nonstandard TPN regimen were more likely to develop raised LFTs. PMID- 1901109 TI - Use of a ventilated canopy for assessment of [13C]leucine oxidation in patients receiving total parenteral nutrition. AB - Rates of oxidation of infused 13C-labeled substrates are calculated from CO2 production and 13C enrichment in breath CO2. Breath sampling through a mouthpiece is not appropriate in severely ill patients; the authors therefore validated the use of direct air sampling from the ventilated canopy of an indirect calorimeter for measuring the oxidation of 13C-labeled substrates. Infusions of H13CO3Na or L [1-13C]leucine were performed in four healthy postabsorptive adults and six malnourished patients receiving total parenteral nutrition (TPN). At each sampling point, air was collected from the canopy to compare with breath air sampled through a mouthpiece and 13CO2 enrichment determined by isotope ratio mass spectrometry. Despite five-fold dilution of expired air by room air within the canopy (a dilution required to maintain safe CO2 levels in inspired air): (1) Breath 13CO2 enrichment was accurately predicted using samples from the canopy, with a correction taking into account the measured CO2 fractions in canopy and room air; (2) the precision in isotopic determination was similar with both methods (SD/mean of 12 determinations = 2.5 +/- 1.0% vs 3.0 +/- 1.0%). These data demonstrate that the use of a ventilated canopy allows for combined assessment of energy expenditure and rates of oxidation of 13C-labeled substrates even in sick, debilitated patients receiving total parenteral nutrition. PMID- 1901110 TI - Infusion of total parenteral nutrition via the umbilical artery. AB - The administration of total parenteral nutrition through umbilical artery catheters in 48 neonates (birth weight 1.7 +/- 0.58 kg) was compared with administration via central venous catheters in 26 infants (birth weight 2.05 +/- 0.89 kg). There was no significant difference in the amount of calories delivered (72 +/- 12 vs 78 +/- 18 cal/kg/day) or in the mean daily weight gain (16.6 +/- 13.3 vs 18 +/- 13.9 g/day). The incidence of sepsis was significantly lower in the umbilical artery catheter group (10.4% vs 15.4%) but there was no significant difference in the rate of infection when adjustment was made for number of days of catheter life (1 per 224 days of catheter life in the umbilical artery group vs 1 per 199 days in the central venous catheter group). Other major complications included transient hypertension in 2 (4%) of the 48 umbilical artery catheter infants and in 1 (3.8%) of the central venous catheter group, aortic thrombosis in 1 (2%) of the 48 umbilical artery catheter infants and a tricuspid vegetation in 1 (3.8%) of the central venous catheter group. Results suggest that the umbilical artery is a reasonable route for the infusion of total parenteral nutrition in low birth weight infants who require arterial access for blood gas analysis. Use of the umbilical artery catheter for parenteral alimentation may avoid the need for surgical placement of central venous lines and the risk of the attendant complications. Nevertheless, safer routes and improved methods of infusion of parenteral infusion must continue to be developed. PMID- 1901111 TI - Risks and benefits of home parenteral nutrition in the acquired immunodeficiency syndrome. AB - The gastrointestinal tract is a major target of the human immunodeficiency virus. Many AIDS patients have weight loss and/or diarrhea. Parenteral nutrition can be used to treat malnutrition associated with malabsorption. We reviewed retrospectively the clinical course of 22 patients with AIDS and weight loss greater than 10% who received home parenteral nutrition (HPN) for 56.2 patient months. Mean weight loss was 21.4%, mean duration of HPN 2.55 months, mean age 37.4 years. Fifteen patients gained weight, six stabilized and two continued to lose weight. Nine patients returned to previous activity. Five died. The rates of catheter-related sepsis, complications, and metabolic disturbances were 0.12, 0.25, and 0.12/100 catheter days, respectively, results identical to those reported in other patient populations where HPN is commonly applied. We found that HPN induced weight gain and clinical improvement in most patients without higher risks of sepsis than in patients with malignancies. PMID- 1901113 TI - A usage evaluation of total parenteral nutrition in pediatric patients. AB - Records of 20 consecutive pediatric patients receiving total parenteral nutrition over a 1-month period were reviewed for appropriateness of nutritional assessment and management. Each patient was monitored until total parenteral nutrition was discontinued or for a maximum of 2 weeks. A total of 124 therapy days were reviewed. Results demonstrated that only 35% of these patients had a nutritional assessment performed prior to initiation of therapy, and only 65% had nutritional goals determined. Nutritional goals were defined as patient-specific goals for fluid volume (FV), calories, protein, and fat emulsion. Analysis of data demonstrated that goals for FV were met on 62% of therapy days. Of the days on which FV goals were met, goals for calories, protein, and fat emulsion were met on 54%, 59%, and 51% of therapy days, respectively. Baseline serum triglyceride levels were measured in one of 20 patients. Serial laboratory monitoring was adequate, with the exception of hepatic enzymes and serum triglycerides, which were measured in 14 and 9 patients, respectively. Recommendations for pediatric parenteral nutrition therapy are discussed, as well as methods to implement these recommendations. PMID- 1901112 TI - Acute effects of continuous nasogastric tube feeding on gastric function: comparison of a polymeric and a nonpolymeric formula. AB - The acute effects of continuous intragastric administration of 1500 ml (4200 kJ/liter) of a polymeric and of a nonpolymeric formula on gastric function were studied in 15 healthy subjects. During 450 min 1500 ml, containing 6300 kJ (1500 kcal), was given through a nasogastric tube. At regular intervals the volume, the pH, the titratable acidity, and the pepsin activity of the gastric contents and the plasma gastrin concentration were determined. Maximal observed intragastric volumes occurred after 120 min (118 +/- 16 ml during polymeric formula, 212 +/- 37 ml during nonpolymeric one) and volumes subsequently halved (at 450 min 68 +/- 13 and 104 +/- 16 ml, respectively). During the administration of both polymeric and the nonpolymeric formula intragastric pH fell progressively to 3.15 and 2.67, respectively, at 450 min. Incremental plasma gastrin values increased between 120 and 450 min from 7 to 12 ng/liter during the polymeric formula. During the nonpolymeric one it stabilized after 120 min at 12 ng/liter. When the whole test periods were considered integrated, mean intragastric volumes tended to be larger during the nonpolymeric formula (153 +/- 23 ml) than during the polymeric formula (107 +/- 12 ml), but this difference was not statistically significant. Median integrated mean pH was lower during the nonpolymeric formula (2.89) compared with the polymeric one (3.26). Despite the limitation that the investigations were performed in healthy subjects only, it is concluded from this study that the risk of aspiration during continuous nasogastric tube feeding is probably greatest during the first few hours of administration because of the larger intragastric volumes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1901114 TI - Safety and efficacy of a new pediatric enteral product in the young child. AB - Children who are unable to maintain an intake of energy and nutrients adequate to meet their needs for growth and maintenance of nutritional status require modifications in feeding. A new pediatric enteral product (PediaSure) was formulated to meet the nutrient needs of children 1 to 6 years of age in a volume that can be tolerated. We designed a noncontrolled, nonrandomized study to evaluate the suitability of this product in young children with respect to growth, protein status, metabolic responses, and gastrointestinal tolerance. Fourteen chronically disabled children were fed the study formula for 12 weeks, receiving daily at least 90% of their estimated energy requirements. Anthropometric measurements and biochemical parameters were obtained throughout the study period. Weight, weight for age, length, weight index, triceps skin fold thickness, mid-arm circumference, mid-arm muscle circumference, and mid-arm muscle area all increased over the study period. Gastrointestinal tolerance and acceptance of the study formula were excellent; there were no clinically significant changes in the biochemical measurements. This study demonstrates that PediaSure is both safe and efficacious in the maintenance of the nutritional status and the promotion of growth in chronically disabled children who require specialized nutritional support. PMID- 1901115 TI - Short-bowel syndrome: a review of the role of nutrition support. AB - Advances in long-term venous access devices and in parenteral nutrition solutions have made it possible for patients with severe short bowel syndrome to survive and to live in our society. The spectrum of this disease is such that some patients may be able to lessen their dependence or even become free from parenteral therapy. This review will discuss the role of nutrition support in the patient with short bowel syndrome. PMID- 1901116 TI - [Acquired coagulopathy caused by administration of parenteral broad-spectrum antibiotics]. AB - Between October 1988 and May 1989, four cancer patients treated by broad-spectrum antibiotics developed a hemorrhagic diathesis induced by vitamin k (VK) deficiency. Activated partial thromboplastin time (APTT), prothrombin time (PT), factor II (FII) and protein induced by vitamin k absence of antagonist-II (PIVKA II) were measured after administration of antibiotics and VK in all 4 patients. All these patients had been receiving intravenous hyperalimentation (IVH) and antibiotics for various infections. But all or them developed hemorrhagic diathesis within five days after the initiation of broad-spectrum cephem antibiotics (LMOX or CMNX). The abnormalities were 1) marked decrease of F II (6 18%), 2) prolongation of APTT (58.4-200 seconds), 3) prolongation of PT (7-21%), 4) marked increase of PIVKA-II (17-80 less than AU/ml). After being treated by intravenous administration of VK, hemorrhagic diathesis and abnormalities of coagulation tests except for PIVKA-II were corrected quickly in three evaluated patients. The measurement of PIVKA-II seemed to be useful to diagnose the hemorrhagic diathesis caused by VK deficiency in the patients during administration of antibiotics. PMID- 1901117 TI - [Effect of GIK solution on the myocardial metabolism]. AB - Effect of GIK solution (50% glucose 100 ml + insulin 20IU + KCl 20 mEq) infused in an hour on the myocardial metabolism was studied in the postoperative period following the open-heart surgery. Increase of arterial glucose, pyruvate, K+ and PCO2 and the decrease of pH was significant at the end of infusion. Increase of coronary sinus blood PCO2, myocardial oxygen extraction ratio for glucose and carbohydrate and the decrease of pH was highly significant. Myocardial oxygen extraction ratio for carbohydrate correlated significantly with the increase of coronary sinus blood PCO2 and the decrease of pH. Although the cardiac index correlated poorly with the myocardial oxygen extraction ratio for carbohydrate, a significant correlation was observed between the coronary arterial-sinus blood K+ difference and the coronary sinus blood PCO2, pH and myocardial oxygen extraction ratio for carbohydrate. It is suggested that the infused glucose with insulin and K+ was metabolized and degraded to CO2 and H2O quickly in the TCA cycle producing ATP and the rest was stored as glycogen with the uptake of K+ in the myocardium. PMID- 1901118 TI - Cost analysis of microsurgical reconstruction in the head and neck. AB - In a cost-conscious environment, pressure exists to justify the use of expensive techniques such as reconstructive microsurgery in head and neck patients. Therefore, the costs and effectiveness of 39 consecutive free tissue transfers in patients with head and neck defects due to neoplasia (77%), trauma (13%), or congenital causes (10%) were assessed by reviewing clinical and billing records. The technical success rate was 95% with a 29% rate of complications. Most patients returned to preoperative levels of social activities, and none admitted dissatisfaction with their results. Average cost was $27,000 per case with 16 days of hospitalization. Average cost for aerodigestive tract tumors was $37,400 with 21 days of hospitalization. Costs were directly related to the etiology of the defect and incidence of complications. Applying cost-effectiveness principles we believe that these costs are justified by the high level of patient satisfaction and enhanced quality of life. PMID- 1901119 TI - Immunohistochemical analysis of plasminogen activator expression in human colorectal carcinomas: correlation with CEA distribution and tumor cell kinetics. AB - Fifty cases of colorectal adenocarcinoma were immunohistochemically examined for the relationship between distribution of plasminogen activators (PAs) and the degree of differentiation of cancer cells as reflected by carcinoembryonic antigen (CEA) expression as well as tumor cell kinetics. The A chain of urokinase type PA (u-PA-A) was mainly observed in the apical portions of highly differentiated cancer cells. Increased expression and change in localization to the cytoplasm were found with progressive dedifferentiation. The numbers of DNA polymerase alpha (pol. alpha) positive cancer cells also increased in line with u PA-A expression. The B chain of u-PA (u-PA-B), and the A and B chains of tissue type PA (t-PA-A and -B) did not show similar alteration. The present findings suggest that the distribution of u-PA-A in colorectal carcinoma tissues, the degree of tumor differentiation, and the proliferation kinetics of cancer cells are closely related. PMID- 1901120 TI - Hypermetabolism after coronary artery bypass. AB - We measured the changes in energy expenditure in the early postoperative phase after coronary artery bypass operations and the ventilatory response to the increased demand for respiratory gas exchange. Breathing pattern and gas exchange were measured noninvasively by respiratory inductive plethysmography and indirect calorimetry with a canopy. Eighteen patients were studied after weaning from mechanical ventilation. Energy expenditure increased by 18.3%, which is comparable to the response to major injury. Carbon dioxide production increased from 162 +/- 20 to 195 +/- 36 ml/min in the supine position (p less than 0.001), and similar changes were observed in the half-sitting position. Arterial carbon dioxide tension increased marginally (37.5 +/- 2.96 mm Hg preoperatively versus 39.7 +/- 4.87 mm Hg postoperatively; p less than 0.05), while oxygen tension decreased from 89.9 +/- 17.3 mm Hg to 62.9 +/- 13.4 mm Hg (p less than 0.001). Minute ventilation increased by 34% in the supine position (p less than 0.01) and by 28% in the half-sitting position (p less than 0.05), while tidal volume remained unchanged. We conclude that coronary artery bypass operations induce hypermetabolism and substantially increase ventilation and risk of arterial hypoxemia during the phase of compromised cardiovascular reserves. PMID- 1901121 TI - Cardiac stun in infants undergoing extracorporeal membrane oxygenation. AB - Previous studies have shown that cardiac performance decreases in infants undergoing extracorporeal membrane oxygenation (ECMO). Some infants have an exaggerated decrease in cardiac performance during ECMO. This syndrome has been called cardiac stun. To better understand this phenomenon, we reviewed the records of infants with cardiac stun and compared them with infants who did not have the syndrome. Cardiac stun was detected in 12 of 240 infants (5.0%) undergoing ECMO. The diagnoses were congenital diaphragmatic hernia (7/12), meconium aspiration syndrome (3/12), respiratory distress syndrome (1/12), and persistent pulmonary hypertension of the newborn (1/12). The weight, gestational age, inotropic support, and time to start of ECMO were similar to infants without cardiac stun. Arterial oxygen tension was lower, carbon dioxide tension was higher, and pH was lower before ECMO in infants in whom cardiac stun developed (p less than or equal to 0.03). Cardiac arrests were more common, before ECMO, in infants in whom cardiac stun developed (6/12; p less than or equal to 0.01). Cardiac stun began at an average 2 1/2 hours after beginning ECMO (range 0.1 to 7 hours). Pulse pressure decreased from 20 mm Hg (range 10 to 45 mm Hg) before stun to 8 mm Hg (range 4 to 12 mm Hg) after stun. Heart rate did not change. Cardiac stun lasted for 33 hours (range 1 to 64 hours) on ECMO and recurred in three infants. Decreases in pump flow and increases in preload, afterload reduction, and inotropic agents did not improve cardiac performance. Survival was lower in the infants in whom cardiac stun developed (p less than or equal to 0.001). Only 5 of 12 infants (42%) survived ECMO when cardiac stun occurred. Our findings show that cardiac stun occurs infrequently during ECMO and is transient in most infants. Infants in whom cardiac stun develops appear to be more ill before ECMO and have a higher mortality after ECMO. PMID- 1901122 TI - Plasma prostanoids in neonatal extracorporeal membrane oxygenation. Influence of meconium aspiration. AB - Thromboxane B2 may be a mediator of neonatal persistent pulmonary hypertension. Elevated levels of plasma thromboxane and prostacyclin have been described previously in hypoxic newborn infants with neonatal pulmonary hypertension. We measured serial plasma levels of thromboxane B2 and 6-keto-prostaglandin F1 alpha (stable metabolite of prostacyclin) in 21 newborn infants with severe respiratory failure and pulmonary hypertension who required extracorporeal membrane oxygenation support. We sought to study (1) the evolution of plasma prostanoids in pulmonary hypertensive infants treated with extracorporeal membrane oxygenation and (2) whether different pulmonary hypertensive diagnostic subgroups have distinctive prostanoid profiles. Our data indicated that infants with meconium aspiration had significantly lower levels of plasma thromboxane B2 and 6 keto-prostaglandin F1 alpha while receiving extracorporeal membrane oxygenation than did infants with persistent pulmonary hypertension but no meconium aspiration. Levels of all infants decreased progressively as extracorporeal membrane oxygenation support continued. PMID- 1901123 TI - Growth properties of cultured human endothelial cells on differently coated artificial heart materials. AB - The cultivation of autologous endothelial cells on the blood surface of artificial hearts might prevent their detrimental thromboembolic complications. To investigate the growth characteristics of endothelial cells on theoretically suitable biomaterials, we compared three polyurethanes (Pellethane, Biomer, Enka) and three silicone rubbers (Elastosil, 3145 RTV, Medical Adhesive). All synthetic surfaces were precoated with an extracellular matrix (group 1), fibronectin (group 2), or a glutaraldehyde-preserved cellular matrix (group 3). After the seeding of 2.5 x 10(4)/cm2 human endothelial cells into the various surfaces, primary adherence, growth kinetics, and maintenance of monolayer integrity were studied for 13 days. On the three polyurethanes all precoating procedures resulted in endothelial cell proliferation and the formation of persistent monolayers. In contrast, on silicone rubbers a persistent coverage with a confluent endothelium could be achieved only on the glutaraldehyde-preserved cellular matrix. When endothelial cell growth was quantitatively assessed on all precoating substrates, the glutaraldehyde-preserved cellular matrix proved to be far superior on each of the synthetics (p less than 0.001). These results demonstrate the theoretical feasibility of endothelialization of artificial hearts in vitro. Provided such an endothelium can withstand the mechanical forces within an artificial heart, in vitro endothelialization might contribute to a regained attractiveness of the elective long-term implantation of artificial hearts. PMID- 1901125 TI - [Is it worth its price?]. PMID- 1901124 TI - Veno-right ventricular bypass as total extracorporeal lung assistance. An experimental study. AB - Efficacy of veno-right ventricular bypass as a total extracorporeal lung assistance was studied for a period of 24 hours in six healthy pigs with a mean weight of 60 kg. A covalently bonded heparin-coated extracorporeal membrane oxygenation system and a roller pump were used for the bypass. No local or systemic heparin was administered. The bypass was established with an open chest with two 28F venous cannulas and one 24F arterial cannula. The arterial cannula was placed in the right ventricle across the tricuspid valve. With the lung function totally disabled, this extracorporeal lung assistance maintained normal systemic arterial and mixed venous blood gases during the entire 24-hour period in all the animals. No significant tricuspid insufficiency was observed, and the animals maintained normal central hemodynamics. There was no hemolysis, and the platelet counts remained essentially unaltered. Multiple foci of clot formation were observed in all the oxygenators, but no macroscopic thrombosis or embolization was seen either in the heart or in the lungs. A veno-right ventricular bypass offers total extracorporeal lung assistance in 60 kg juvenile pigs for a period of 24 hours. Tricuspid valve competence is an important prerequisite for the success of this procedure. PMID- 1901126 TI - [A new method increases analytic capacity in the control of diabetics]. PMID- 1901128 TI - The human thyrotropin-releasing hormone gene: an application of molecular biology to contemporary endocrinology research. PMID- 1901127 TI - Cytokine stimulated endothelin release from endothelial cells. AB - Endothelin release from bovine endothelial cells of the aorta, pulmonary artery, and retinal microvessels was measured in response to various cytokines. Transforming growth factor beta (0.05-5 ng/ml) was found to be a potent stimulator (3-4 fold increase) of endothelin secretion in all three cell types. Tumour necrosis factor alpha (0.1-10 ng/ml) and interferon gamma (8-800 U/ml) had a small (1.5-2 fold increase) but significant effect on endothelin secretion from endothelial cells of large vessels but not the retinal microvessels. Interleukin 1 beta, Interleukin-6 and interleukin-8 at various doses did not affect endothelin secretion. These effects were observed at various time points from 6 24 hrs and indicate that of the cytokines tested, only transforming growth factor beta has a potent effect on endothelin release from endothelial cells of different organs. PMID- 1901129 TI - Comparison of IAEA 1987 and AAPM 1983 protocols for dosimetry calibration of radiotherapy beams. AB - The IAEA 1987 protocol is an international protocol which has made a number of improvements over the AAPM 1983 protocol for calibration of high-energy photon and electron beams. We present a detailed numerical comparison between the two protocols by calculating (i) Ngas and ND for PTW (PMMA wall), Capintec (air equivalent plastic wall) and NEL (graphite wall) Farmer type ionization chambers for 60Co gamma rays; (ii) dose-to-water with chamber in water irradiated by 4- or 25-MV x rays; (iii) dose-to-water with chamber in water, PMMA, and polystyrene phantoms irradiated by 5- and 10-MeV electrons; and (iv) dose-to-water with chamber in water irradiated by 20-MeV electrons. For photons, the IAEA protocol gives results which are in good agreement with the AAPM protocol; on average the IAEA results are 0.6% smaller than the AAPM results while discrepancies between the two are in the range of -0.4% to -1.2%. For 10-MeV electrons also, the IAEA protocol gives results which are in excellent agreement with the AAPM protocol; on average the IAEA results are 0.3% smaller than the AAPM results while discrepancies between the two are in the range of -1.0% to +0.5%. In contrast to the above, for 5-MeV electrons, the IAEA protocols give results smaller than the AAPM protocol by 2.0% on average with discrepancies between protocols ranging from -4.1% to -0.7% depending upon the ionization chamber and phantom material used. For 5-MeV electrons, the discrepancies are particularly large for polystyrene phantom; the average discrepancies being -1.4%, -1.1%, and -3.6% for water, PMMA, and polystyrene, respectively. If data for 5-MeV electrons with polystyrene phantom are excluded, then the overall agreement between the two protocols for photons and electrons is within the range of -1.9% to +0.5%. Principal reasons for the observed discrepancies are (i) IAEA uses the correct expression for ND resulting in up to +0.8% correction; (ii) IAEA uses the most recent stopping power ratio for graphite-to-air resulting in up to +0.5% correction; (iii) IAEA uses a correction of up to +0.8% for the central electrode which AAPM ignores; (iv) the present estimates of the percent depth doses which arise from the differences in measurement depths in the two protocols; and (v) IAEA uses measured values of the fluence correction factor while AAPM uses a theoretical estimate resulting in corrections of up to -2.2%. PMID- 1901131 TI - Demonstration of three-dimensional deterministic radiation transport theory dose distribution analysis for boron neutron capture therapy. AB - The Monte Carlo stochastic simulation technique has traditionally been the only well-recognized method for computing three-dimensional radiation dose distributions in connection with boron neutron capture therapy (BNCT) research. A deterministic approach to this problem would offer some advantages over the Monte Carlo method. This paper describes an application of a deterministic method to analytically simulate BNCT treatment of a canine head phantom using the epithermal neutron beam at the Brookhaven medical research reactor (BMRR). Calculations were performed with the TORT code from Oak Ridge National Laboratory (ORNL), an implementation of the discrete ordinates, or Sn method. Calculations were from first principles and used no empirical correction factors. The phantom surface was modeled by flat facets of approximately 1 cm2. The phantom interior was homogeneous. Energy-dependent neutron and photon scalar fluxes were calculated on a 32 x 16 x 22 mesh structure with 96 discrete directions in angular phase space. The calculation took 670 min on an Apollo DN10000 workstation. The results were subsequently integrated over energy to obtain full three-dimensional dose distributions. Isodose contours and depth-dose curves were plotted for several separate dose components of interest. Phantom measurements were made by measuring neutron activation (and therefore neutron flux) as a function of depth in copper-gold alloy wires that were inserted through catheters placed in holes drilled in the phantom. Measurements agreed with calculations to within about 15%. The calculations took about an order of magnitude longer than comparable Monte Carlo calculations but provided various conveniences, as well as a useful check. PMID- 1901130 TI - Accelerated helium-ion beams for radiotherapy and stereotactic radiosurgery. AB - A new beam line for radiotherapy and radiosurgery with accelerated helium-ion beams has been set up at the Bevalac. The new treatment room has been equipped with a very precise patient positioner in order to utilize the superior dose localization properties of light-ion beams. The beam spreading and shaping system is described, the trade-offs involved in positioning the beam modifying devices are discussed, and the physical properties of the generated radiation fields are reported. The Bragg peak modulation by axial beam stacking employing a variable range shifter is explained and the control system including beam monitoring and dosimetry is presented. PMID- 1901133 TI - Economic cost of diabetes mellitus--Minnesota, 1988. AB - For diabetes mellitus (DM) and other chronic diseases, important indicators of disease burden include morbidity, mortality, measures of disability and quality of life, and economic burden. Because of limited data, however, the economic burden of DM has been difficult to measure. Although national costs for DM have been estimated recently (1-5), state-specific estimates have, in general, not been possible. This report summarizes an analysis prepared by the Minnesota Diabetes Surveillance Project (MDSP), Minnesota Department of Health, that estimated the economic impact of DM in Minnesota for 1988. PMID- 1901132 TI - Clinical electron-beam dosimetry: report of AAPM Radiation Therapy Committee Task Group No. 25. PMID- 1901134 TI - Update: influenza activity--United States and worldwide, and the composition of the 1991-92 influenza vaccine. PMID- 1901135 TI - Availability of NIOSH criteria document on ethylene glycol monobutyl ether and ethylene glycol monobutyl ether acetate. PMID- 1901136 TI - Rabies prevention--United States, 1991. Recommendations of the Immunization Practices Advisory Committee (ACIP). PMID- 1901137 TI - Acquired factor VIII deficiency and polyradiculoneuropathy. PMID- 1901138 TI - Incidence of human tuberculosis caused by Mycobacterium bovis. PMID- 1901139 TI - Hepatitis C. PMID- 1901141 TI - Jugular bulb diverticula. AB - Jugular bulb diverticula may extend either laterally in the tympanic cavity or medially towards the petrous pyramid close to the inner ear. In the first case, this leads to subjective symptoms related to the presence of a mass at the level of the tympanic cavity and the external auditory canal and thus to conductive hearing loss and pulsatile tinnitus. In the second case, vertigo, pulsatile tinnitus and sensorineural hearing loss occur. 4 cases of jugular bulb diverticula are described (1 medial type, 3 lateral type). PMID- 1901142 TI - Historical ties between otolaryngology--head and neck surgery and space medicine. AB - Otolaryngologist--head and neck surgeons have been involved in the development of aviation and space medicine since the beginning of this century. In the late 1910s, otolaryngologists revised the physical examination for pilots, organized "Boards of Medical Examiners" to test pilot applicants, coined the term "flight surgeon," and helped organize the Medical Research Laboratories at Hazelhurst Field in New York. These laboratories were transformed into the School of Aviation Medicine at Brooks Field, Texas, which was relocated to Randolph Field, Texas, in 1934. During World War II, the director of research at the school was Colonel Paul A. Campbell, MD, an otolaryngologist. In 1959 the school moved back to Brooks Air Force Base and was renamed the Aerospace Medical Center. In 1962, Dr. Campbell served as the director. Since manned space flight began in the 1960s, there have been many joint research efforts between principal investigators in otolaryngology--head and neck surgery and NASA. Currently, many otolaryngologist--head and neck surgeons serve as consultants and advisors to many of NASA's standing committees. The space environment offers a new frontier for specialty development and research in otolaryngology--head and neck surgery. PMID- 1901140 TI - Experimental labyrinthitis in guinea pigs caused by a hantavirus. AB - Hantavirus-induced acute viral infection of the inner ear of guinea pigs is reported. Guinea pigs were inoculated directly into the inner ear through the round window, or intraperitoneally with hantavirus (B-1 strain), and the cochlea was examined using an immunohistochemical technique for the localization of viral antigens. Virus-specific antigens were detected prominently in the stria vascularis and to a lesser degree in other inner ear structures of the infected guinea pigs. The morphological changes in the inner ear structures of these guinea pigs were observed. Virus was isolated from the blood of some infected guinea pigs. These data suggest that hantavirus can infect the inner ear of the guinea pig via viremia. The effect of immunosuppression by ciclosporin A or cyclophosphamide is discussed. PMID- 1901143 TI - A homily for physicians. PMID- 1901144 TI - Acoustic-distortion products: separation of sensory from neural dysfunction in sensorineural hearing loss in human beings and rabbits. AB - Because distortion-product otoacoustic emissions (DPOAEs) provide a noninvasive measure of outer hair-cell (OHC) activity, they should provide a unique and sensitive indicator of the effects of agents that damage hearing. Using DPOAE methods, the present study was designed to assess the relative contributions of the cochlea's outer hair cells to some common sensorineural diseases, including Meniere's disease, acoustic neuroma, and noise-induced, hereditary, and sudden idiopathic sensorineural hearing loss. Parallel evaluations of DPOAEs were performed under essentially identical conditions in rabbit models of several of the human disorders, including noise-induced hearing loss, endolymphatic hydrops, and cochlear neurectomy. Animal studies were performed to assess the proficiency of DPOAEs to track a developing sensorineural deficit as well as to compare patterns of DPOAE dysfunction between clinical and experimental forms of peripheral hearing loss. Detailed measures of DPOAEs were collected in the stimulus-frequency and intensity domains as "audiograms" and response/growth or input/output functions, respectively. The outcome of analyses of both human beings and animals supported the notion that DPOAE testing is sensitive to sensory-cell disease. Thus, in combination with conventional audiometry, DPOAE measures permit a distinction between the relative contribution sensory and neural components of the cochlea make to hearing deficits. PMID- 1901145 TI - A modified neoglottis procedure: update and analysis. AB - In recent years, various techniques have been introduced for construction of an epithelium-lined shunt between the trachea and the esophagus or hypopharynx. We described a rigid neoglottis in a preliminary report of 12 cases in which the upper tracheal rings were used to construct the epithelium-lined tract. This study reports the cases of 22 additional patients and offers an in-depth analysis of additional demographics, complications, and long-term speech results that quantify the vocal characteristics of neoglottic speakers. Results indicate rapid postoperative speech rehabilitation in nearly all patients, good long-term speech results (mean followup, 52 months), and low morbidity. There was a low incidence of local recurrence and stenosis, and 26 of 34 patients had either no aspiration or occasional asymptomatic aspiration of small amounts of liquid. This modified neoglottis procedure should be considered for patients who need voice restoration after laryngectomy. PMID- 1901146 TI - Comparison of computerized tomography and magnetic resonance imaging for the postoperative assessment of residual acoustic tumor. AB - Ten patients with surgically confirmed residual cerebellopontine angle neuromas, imaged by both computerized tomography (CT) with iodine contrast and magnetic resonance (MR) with and without gadolinium enhancement, are reviewed to identify the strengths and limitations of MR as compared with CT imaging. MR imaging offers superior anatomic resolution in multiple imaging planes without ionizing radiation, but it is expensive and has adverse effects on some patients. CT imaging offers good anatomic resolution, but in only one or two planes. CT is both less expensive and generally well tolerated, but allergy to the iodine contrast is not uncommon. The cases presented demonstrate the adequacy of CT imaging of residual tumor. However, in some cases MR imaging provided important additional detail. MR imaging also demonstrated postoperative changes within the brain stem and cerebellum. In our experience, CT imaging remains a satisfactory, unambiguous approach to the assessment of known postoperative residual cerebellopontine angle neuromas. MR imaging provides superior resolution, however, and should be used when better definition of tumor detail is needed for management decisions or when multiple follow-up scans are anticipated, so that the exposure to ionizing radiation is limited. MR is also useful to investigate postoperative neurologic dysfunction. Postoperative changes and residual tumors are more difficult to interpret on MR than on CT. Guidelines are proposed to help distinguish residual tumor from postoperative changes and scarring. PMID- 1901147 TI - Otolaryngology problems in the immune compromised patient--an evolving natural history. AB - As the human immunodeficiency virus is being detected in increasing numbers of asymptomatic individuals at risk, newer earlier patterns of disease have become apparent--including cranial and cervical herpes zoster, oral hairy leukoplakia, and oral candidiasis--thus linking viral and other disease to the development of acquired immunodeficiency disease (AIDS). Many similarities between patients with AIDS and other immunosuppressed patients have emerged. As immunosuppressed patients survive longer, they begin to manifest cancers such as lymphomas and squamous cell cancers in addition to Kaposi's sarcoma. Otolaryngologists can learn to identify and treat otitis and sinusitis in the immunosuppressed patient, to identify predictive early signs such as oral hairy leukoplakia, herpes simplex virus, and oral candidiasis, and to diagnose and treat Kaposi's sarcomas of the head and neck, lymphomas, squamous cell cancers, and opportunistic infections as the immunodeficiency disease progresses. PMID- 1901148 TI - Internal maxillary artery variability in the pterygopalatine fossa. AB - The third segment or pterygopalatine branch of the internal maxillary artery has variable branching in the pterygopalatine fossa. This variability in branching can lead to failure in controlling persistent nasal epistaxis by transantral ligation. Although the surgical approach has been previously studied, a systematic classification of this branching has not been previously reported. Through the performance of serial cadaver dissections in the PPF, we have demonstrated the anatomic course and variations of this third segment and offer a relatively simple classification system. PMID- 1901149 TI - A universal ossicular replacement prosthesis: clinical trials of 152 cases. AB - An ossicular replacement prosthesis is described that advances implant design in several respects. The head is a flattened egg shape, which eliminates pressure points against the pars tensa and provided balance on the stapes. Dense hydroxylapatite ceramic provides maximal biocompatibility. The shaft, of either Teflon or Plastipore, is easily cut to size and is replaceable to minimize wastage. Interchangeable partial or total shaft variants are provided. Trials in more than 200 patients have produced optimal results. Among 152 mature patients in 85% of the good-risk cases, the air-bone gap closed to within 20 dB and in 65% to within 10 dB; in 69% of all cases the gap closed to within 20 dB. Extrusion rates were 5% in good-risk cases and 7% overall. Long-term extrusions have not occurred. Inasmuch as cartilage interpositioning is unnecessary, the prosthesis is rapidly prepared and implanted by an easily mastered technique. PMID- 1901151 TI - Radiographic evaluation and diagnosis of the failed frontal osteoplastic flap with fat obliteration. AB - In the absence of evidence of suppurative disease, clinical assessment of the symptomatic patient after frontal osteoplastic flap with fat obliteration is difficult because the cause of the pain is often neuralgic or from chronic vascular headache. Among 59 patients who have undergone this procedure at our institution since 1979, four required revision surgery. These patients were evaluated by computed tomographic and magnetic resonance scans, and the radiographic findings were compared with those present in 20 asymptomatic subjects. On the basis of the results of this study, we believe we can objectively identify those patients with chronic pain in whom the operation has been unsuccessful. A review of our experience with this procedure is presented along with criteria that enable early diagnosis of recurrent disease in the frontal sinus after osteoplastic sinusotomy. PMID- 1901150 TI - The electrically evoked vestibulo-ocular reflex: I. Normal subjects. AB - Recent animal studies indicate that electric currents applied through perilymphatic-space electrodes stimulate vestibular primary afferent neurons directly. These findings suggest that electrical stimulation may provide a testing method by which the vestibular nerve and central pathways could be evaluated separately from the vestibular end-organ. The goal of this study was to obtain normative data on human beings for an electrically evoked vestibulo-ocular reflex (EVOR). Sinusoidal electrical stimuli (0.0125 to 0.8 Hz, 4 mA peak intensity) were applied along the interaural axis through mastoid electrodes in 10 subjects. Horizontal eye movements were recorded by an infrared limbus tracking device. The subjects also underwent rotational stimulation at the same frequencies so that their horizontal vestibulo-ocular reflex (VOR) could be evaluated. Nystagmus was observed in the EVOR at lower stimulus frequencies, whereas purely sinusoidal eye deviations occurred at higher frequencies. The phase of the EVOR slow-component eye velocity consistently lagged the stimulus. This contrasts with the phase measurements of the VOR in the same subjects, which exhibited a lead relative to head velocity. These findings suggest that currents applied to human beings may activate vestibular primary afferents independent of peripheral receptor mechanisms and thereby provide a "site-of-lesion" testing method by which the vestibular nerve and central pathways can be evaluated separately from the vestibular end-organ. PMID- 1901152 TI - The intracutaneous progressive dilution multi-food test. AB - Data have been published supporting the view that skin response is more valid and reliable than symptom provocation for interpretation of the intracutaneous provocative food test (IPFT). As such, an intracutaneous progressive dilution food test technique interpreted by skin response is now the standard IPFT technique taught at American Academy of Otolaryngic Allergy-sponsored courses. While this test technique is less time-consuming than the 5-day oral challenge food test of Rinkel, the 15- to 90-minute per test demand still presents a significant deterrant to widespread use. Here we present a time-efficient, multi test technique that allows testing of three to seven foods at one time. The technique is not recommended for use on patients with a history of severe allergic reactions, such as asthma or angioedema, or for testing any food that by history may produce an anaphylactic reaction. PMID- 1901153 TI - Perilymph fistulas: the House Ear Clinic experience. AB - The diagnosis, evaluation, and surgical treatment of perilymph fistulas has recently been the focus of a great deal of attention in otology. Authors have focused on perilymph fistulas as the cause of hearing loss and vertigo in many diverse situations. Additionally, surgical repair has been suggested when there is little objective support for intervention. To address some of the problems inherent in the diagnosis and treatment of perilymph fistulas, records of patients operated on at the House Ear Clinic during the past 12 years were reviewed retrospectively. Eighty-six patients were surgically explored for fistulas during this period. Thirty-five (40.7%) fistulas were found, and 51 ears were patched whether fistulas were found or not. Of the 80 patients who were seen for follow-up, 35 (43.8%) were subjectively better, and 45 (56.2%) were the same. Although the number of fistulas found and the number of patients improved were similar, the composition of the two groups was different. On the basis of audiometric results, improvement in hearing occurred in only 18.7% of the patients. None of the demographic factors or diagnostic tests were predictive of either the presence of a fistula or the therapeutic outcome. Further work is required to facilitate the preoperative diagnosis of fistulas and to design appropriate surgical intervention. PMID- 1901154 TI - Endoscopic sinus surgery: outcome in 155 cases. AB - For this retrospective study of endoscopic sinus surgery, charts of 22 patients from a medical center and 133 patients from a private practice (N = 155) were reviewed. Preoperative complaints, clinical findings, computed tomographic evidence of extent of sinus disease, surgical outcome, possible predictors of success, and complications were considered. Indications for endoscopic surgery were persistence of symptoms despite aggressive medical therapy and radiologic evidence of a significant sinus abnormality. Median followup was 12 months. Hemorrhage occurred postoperatively in two patients (1.5%); 17 patients required additional endoscopic surgery. Overall, 140 (91%) patients believed that the surgery was beneficial. Patients with facial pain preoperatively showed the greatest improvement. All patients having simultaneous septoplasty (N = 64) had successful outcome. The total number of opacified sinuses was not a predictor of outcome, but opacificaiton of the sphenoid sinus correlated with a poorer outcome. The patients seen at the medical center had poorer results, but had a larger number of opacified sinuses, were more likely to have had previous sinus surgery, and were more likely to have underlying medical conditions contributing to their sinus disease. PMID- 1901155 TI - The potassium--titanyl phosphate laser for treatment of turbinate dysfunction. AB - Patients with nasal turbinate dysfunction most often are seen by the physician with such symptoms as watery nasal secretions, nasal obstruction, congestion, facial pressure, or pain. There will often have been multiple attempts to manage the problem medically and symptomatically with antihistamines, decongestants, antibiotics, nasal cromolyn, and topical or systemic steroid therapy. Some patients will have undergone numerous attempts at surgical therapy, most often with cryosurgery or cauterization. The cause of the symptoms of turbinate dysfunction for most of these patients is either vasomotor rhinitis, allergic rhinitis, or polypoid hypertrophic turbinates. A visible-wavelength laser with a wavelength of 532 nm, the potassium-titanyl phosphate laser has been used with nasal endoscopes to perform laser photocoagulation of the nasal turbinates. A description of the technique and early results have been previously reported. This article reports good long-term results with the technique. PMID- 1901156 TI - Osteomyelitis of the skull base, etiology unknown. AB - OSB can occur in the absence of an obvious contiguous source of infection. When a patient has persistent unilateral headache, elevated ESR, and radiographic evidence of a lytic skull-base lesion, the clinician should consider OSB as a potential diagnosis. A baseline gallium scan should be obtained before biopsy, since surgery or trauma can also produce positive results on radionuclide scans. Technetium-phosphate bone scans should also be performed before any surgical manipulation. However, positive results from a gallium or technetium scan in this setting are not conclusive evidence of infection. At biopsy, the otolaryngologist head and neck surgeon should consider sending a specimen to the microbiology department for culture in addition to the specimen sent for routine pathologic study; this procedure could minimize delay in diagnosis. Establishing the diagnosis in these patients without obvious contiguous infection can be difficult, demanding perseverance and an appropriate index of suspicion. Once the diagnosis is confirmed, intravenous antibiotic therapy should begin immediately. The duration of therapy must be individualized; patients may require from 4 weeks to several months of treatment. Response to therapy is indicated by resolution of symptoms, normalization of ESR, and reversal of abnormalities on radionuclide scans. Serial gallium scans are particularly useful in following response to treatment. PMID- 1901157 TI - Extraskeletal myxoid chondrosarcoma of the epiglottis: case report and review of the literature. PMID- 1901158 TI - Metastatic glomus jugulare: long-term followup. PMID- 1901159 TI - Sudden hearing loss due to AIDS-related cryptococcal meningitis--a temporal bone study. AB - We have presented the clinical history and temporal bone findings in a patient who manifested sudden hearing loss, and who subsequently was found to have cryptococcal meningitis associated with AIDS. The histopathologic findings are similar to earlier reports in patients without AIDS. Because cryptococcal infection is so much more common in AIDS patients than in the general population, it must be considered a causative factor when presented with an AIDS patient with progressive or sudden hearing loss. This offers the patient a chance for timely and effective treatment. PMID- 1901160 TI - Medial maxillary fractures. PMID- 1901161 TI - Intrasphenoidal encephalocele. PMID- 1901162 TI - Acoustic neuroma. PMID- 1901163 TI - Aggressive fibromatosis. PMID- 1901165 TI - Choice of lasers for minimally invasive spinal surgery. AB - Recently, there has been increased interest in less invasive spinal surgery techniques. This has led to the development of procedures such as automated percutaneous lumbar discectomy and arthroscopic microdiscectomy. Lasers are now used in many areas of medicine and may have applications in minimally invasive spinal surgery. A number of different laser systems have been evaluated for their effectiveness in removing disc tissue in the laboratory, but technical problems have limited their clinical use. Only the Nd:YAG (1,064 nm and 1,320 nm) and KTP (532 nm) systems have been used clinically. Unsuccessful clinical results were obtained with the 1,064 nm Nd:YAG, whereas the other two systems appeared to produce results similar to the present mechanical systems but required less time for disc removal. This paper discusses considerations for choosing a laser system for spinal applications and reviews the work performed in this area. PMID- 1901164 TI - Phonosurgery--a classification. PMID- 1901166 TI - A novel remit. PMID- 1901167 TI - Nutrition support of critically ill patients. Guidelines for optimal management. AB - Nutrition support is an important component of the management of critically ill patients. Before support is initiated, realistic goals should be established and risks and benefits considered. Initially, hemodynamic status should take precedence over nutritional status. Enteral feeding is the preferred route when the gastrointestinal tract is functioning. In most cases calorie requirements can be estimated adequately with use of the Harris-Benedict equation. Indirect calorimetry provides valuable information in patients with impending respiratory failure; withdrawing excess calories and substituting lipid calories for carbohydrate calories, if necessary, may be beneficial. Clinical response can be assessed by nitrogen balance studies and weekly measurement of weight and serum transferrin levels. PMID- 1901168 TI - Recruitment strategies for a possible tamoxifen trial. AB - Participants in a primary prevention trial using tamoxifen to prevent breast cancer should comprise a sample of (a) age-eligible women from the "general population," (b) higher risk sisters of breast cancer patients, (c) women participating in mammography screening programs, or (d) patients of (or other users of) primary care physicians' offices. The recruitment should consider the risk of breast cancer among eligible women, likelihood of adherence to protocol, and unbiased and accurate measurement of endpoints. The Risks for coronary heart disease, hypertension, diabetes, osteoporosis, and other cancers, especially uterine cancer, must also be evaluated. Recruitment is feasible and should not be the limiting factor in the decision to undertake a primary prevention trial. PMID- 1901169 TI - Reduction of enhanced mammary carcinogenesis in LA/N-cp (corpulent) rats by energy restriction. AB - Restriction of energy intake significantly reduces mammary tumorigenesis in normal rats exposed to carcinogens. Genetically obese LA/N-cp (corpulent) female rats were given 7,12-dimethylbenz[a]anthracene and fed purified diets ad libitum or restricted to 60% of the ad libitum caloric intake. Phenotypically lean littermates were also fed ad libitum. Obese animals developed large mammary tumors more rapidly than genetically normal rats so that 100% of the animals had tumors in less than 16 weeks. Only 21% of the lean animals developed tumors; the energy restricted obese animals had a tumor incidence of 27%. Although obese rats fed the restricted diet weighed significantly less than those fed ad libitum, percent body fat was not reduced, indicating that lean tissue was affected more. Obese animals were markedly hyperinsulinemic (1003 +/- 193 microunits/ml) and energy restriction reduced this to 328 +/- 41; the lean animals had insulin levels of 12 +/- 2. Tumor-bearing rats had higher insulin levels than rats without tumors. These data suggest that body fatness is not directly associated with risk of carcinogenesis. Lean body mass, adipose tissue mass, and their interaction with insulin in its capacity as a growth factor rather than body fatness per se may be determinants of tumor promotion. PMID- 1901170 TI - Apparent role of adenosine diphosphoribosyl transferase in the development of Mytilus edulis and the inhibition of differentiation by ligands of the enzyme protein. AB - The poly(ADP-ribose) polymerase or transferase (ADPRT) activity of developing embryos of Mytilus edulis increases with the progression of larval growth. ADPRT protein was partially purified from 2-hr-old embryos and identified by gel electrophoresis and immunotransblot, demonstrating cross-reactivity with anti ADPRT IgG produced against the calf thymus enzyme. Two inhibitors of ADPRT, benzamide, competing with NAD at the nicotinamide binding site, and 6-amino-1,2 benzopyrone, which competes with DNA at the DNA binding site(s), both selectively arrest differentiation at the prodissoconch stage. The DNA site-oriented inhibitor, 6-amino-1,2-benzopyrone, has a much larger differentiation arresting effect than benzamide. The arrest of differentiation by 6-amino-1,2-benzopyrone is reversible. A probable ecotoxicity of ADPRT ligands on mussel differentiation is proposed. PMID- 1901171 TI - Intercomparison of whole-body counters using a multinuclide calibration phantom. AB - Whole-body counters in the UK have been compared using a multinuclide anthropomorphic phantom. A standard Bush phantom was modified by inserting channels into the long axis of each section. Radionuclide sources sealed in a urea-formaldehyde polymer were then inserted into the channels to simulate distributions of radioactivity in a human. The phantom was taken to 10 whole-body counters in the UK and estimates of 134Cs, 137Cs and 40K were obtained both separately and as mixtures. Results showed close agreement between the median estimates and the known activities. The technique also allowed diagnosis of particular problems in calibration for several of the counters. PMID- 1901172 TI - Which depth dose data should be used for dose planning when wedge filters are used to modify the photon beam? AB - The use of beam data for open photon fields when calculating absorbed dose distributions for beams with wedge filters has been studied. The depth doses for beams with wedge filters are changed through beam hardening and the dose maximum can be shifted; both these changes result in errors in the final dose calculations of several per cent if open beam data are used. The errors are larger for 6 MV than for 18 MV x-rays. The depth of measurement for determining the wedge factor and the influence of other beam modifying devices are discussed. It is recommended that the reference depth be used instead of the dose maximum for these kinds of measurements since the influence of contaminating electrons in the beam will then be avoided and the wedge factor will be correct at a clinically relevant depth. PMID- 1901173 TI - Molecular biology of the hemophilias. PMID- 1901174 TI - [Language and thought]. AB - Mixing, however briefly, with aphasic subjects is sufficient to show that though survives language alterations. Everyone's experience of forgetting proper names and common nouns clearly shows that concepts outlive words. Analyzing puns and allusions also reveals that the meaning of a word depends on a context of signification which may or may not be supplied verbally. Studying thought without language in both animals and infants provides evidence not only that language facilitates the exercise of cognitive functions but also that the initial progress facilitates the exercise of cognitive functions but also that the initial progress made by children is not related to language but to brain maturation. Dealing with the question of right hemisphere performance in patients with a brain split by callosotomy demonstrates, better than anything else, that each position taken on this question is underlain by philosophical presuppositions. In contradistinction with philosophies derived from that of Wittgenstein and from logical positivism and functionalist cognitivist theories, the author argues that all we know is through and within our thought, that all we say is thought and that, consequently, no scientific, philosophical, poetical or other discourse is able to apprehend or restrain thought. Thought extends far beyond language, including scientific language. PMID- 1901175 TI - [Diagnosis of viral hepatitis in 1991]. AB - Viral hepatitis is a disease which is frequent but often asymptomatic and therefore remains unrecognized until a late stage. Hence the importance of biochemical and, chiefly, virological detection in populations at risk such as transfusion recipients, drug addicts or exposed professionals. Detection is based on systematic transaminase assays during check-ups or in the presence of warning signs. Any rise in transaminase level must lead to serological examinations in search of the A, B, C and Delta markers. Routine vaccination of subjects at risk against hepatitis B should considerably reduce the prevalence of this disease and of Delta hepatitis in the populations exposed. PMID- 1901176 TI - [Sequelae of severe craniocerebral injuries. An epidemiological study in the Canton of St. Gallen]. AB - Severe head injuries often lead to serious medical and socioeconomic sequelae. The incidence rate indicated in other studies shows a wide variation due to differences in selection criteria. Based upon an unselected population, the incidence of severe head injury was calculated and the surviving patients were interviewed and clinically examined 3 years after the accident in order to describe the course, rehabilitation and psychosocial sequelae after severe head injury. Retrospectively we collected 80 patients living in the canton of St. Gallen who had a severe head injury requiring hospitalization in 1987, indicating an incidence of 20 per 100,000 inhabitants. 22 (28%) of these patients died as a consequence of the head trauma. The best predictor was the Glasgow coma score at admission, which showed a highly significant direct correlation with survival rate. Regarding the degree of impairment of survivors the duration of posttraumatic amnesia was the best predictive parameter. Of the 45 patients controlled 3 years after the head trauma only 11% were severely impaired in daily activities. 79% of the patients who were gainfully employed before the accident were working full- or at least part-time. However, only 3 patients (7%) were absolutely free of symptoms. Most patients suffered from cognitive and emotional deficits. Based on an estimated incidence for minor head trauma of 174 per 100,000 inhabitants, a total annual incidence for all head traumas of 194 per 100,000 inhabitants is calculated, with severe head injury representing about 1/9 of all head injuries. PMID- 1901177 TI - Program optimization: a semi-quantitative approach. AB - The authors describe a quantitative model used to express the relative costs and benefits of alternative approaches to pulmonary prevention. This approach identifies the factors that a program director must consider in planning preventive interventions for respiratory disease of workers. PMID- 1901179 TI - Primary malignant melanoma of the gasserian ganglion associated with neurofibromatosis. AB - A case of primary intracranial malignant melanoma of the left gasserian ganglion associated with temporal lobe gliosis in a patient suffering from von Recklinghausen's disease is reported. The association of primary malignant melanoma of the trigeminal nerve and neurofibromatosis is discussed. PMID- 1901178 TI - Metastatic angiosarcoma of the brain. AB - Two patients with metastatic angiosarcoma of the brain are described. In one, a 17-year-old man, the tumor was located at the pineal region and exhibited significant vascularity. It was sensitive to radiation therapy and disappeared after radiation of 50 Gy; however, it recurred after 1 year and a new lesion was found in the liver. The other patient is a 31-year-old woman who experienced sudden onset of headache. Computed tomography scan revealed three separate masses in the brain. One tumor was surgically removed. The other two were sensitive to radiation therapy and disappeared after radiation of 40 Gy. A new lesion was found in the femur 16 months after the operation. Brain metastasis from angiosarcoma is exceedingly rare. Both patients developed symptoms with intracranial hemorrhage. The diagnosis of the metastatic lesions preceded diagnosis of the primary lesion by 12 and 16 months, respectively. Ulex europaeus 1 lectin and factor VIII were very useful in establishing the diagnosis of angiosarcoma. PMID- 1901180 TI - Xanthoma in Meckel's cave. A case report. AB - A case of xanthoma located within Meckel's cave and the semilunar ganglion is described in a patient with a trigeminal nerve deficit. This is the first case of xanthoma in such a location. The distinctive morphological appearance is illustrated and the possible histogenesis is discussed. PMID- 1901181 TI - [Prolonged action nitrates in stable angina pectoris]. AB - A randomized double blind comparison of transdermal nitroglycerin and isosorbide dinitrate tablets was conducted in 100 men with stable angina pectoris. Subjective and objective effects were virtually identical for both regimens (number of angina attacks/nitroglycerin consumption and exercise ECG test variables). The pattern of side effects was also similar for both drugs. A considerable dissociation was observed between subjective effects and effects measured by ergometer test in the individual patient. Lack of both subjective and objective effects--i.e. nitrate tolerance--was observed in approximately one fourth of the patients, and was not prevented by a twelve-hour dosing interval on isosorbide dinitrate nor a six hour transdermal nitroglycerin-free interval. Our data lends credence to the notion that the effects of long-acting nitrates in daily life and the effects measured during stress testing may involve different mechanisms. PMID- 1901182 TI - [Diphtheria in Denmark 1956-1989. Occurrence of Corynebacterium diphtheriae and other diphtheria toxigenic bacteria]. AB - The public immunization program against diphtheria, established in 1941, has almost eradicated the disease in Denmark, and 1956 became the first year without any notified cases. Since then, toxigenic strains have only been isolated five times--three cases of clinical diphtheria due to Corynebacterium diphtheriae biovar. mitis and two cases of tonsillitis/pharyngitis due to Corynebacterium ulcerans. The source of the infection was not identified in any of the cases. The first case of diphtheria in 1968 was imported from abroad. The following two cases in 1983 and 1985 were due to strains of the same phage type and peptide profile as the strains isolated during the epidemic in Sweden in 1984-1986. This indicates that the Danish cases and the Swedish epidemic derived from the same source. The diphtheria immunity of the Danish population is decreasing, and the level of protection is approaching the Swedish level. The impact is that a situation like that in Sweden may be anticipated with diphtheria epidemic in the lowest socio-economical groups--the skid row dwellers, alcoholics and drug abusers--if the immunization program against diphtheria is not intensified. PMID- 1901183 TI - Analgesia in dogs after intercostal thoracotomy. A comparison of morphine, selective intercostal nerve block, and interpleural regional analgesia with bupivacaine. AB - Three postoperative analgesic protocols were assigned randomly to 24 healthy dogs after thoracotomy at the left fourth intercostal space. Morphine was administered parenterally to eight dogs after tracheal extubation; selective intercostal nerve blocks with bupivacaine hydrochloride and epinephrine were administered to eight dogs before closure of the thorax; and bupivacaine hydrochloride and epinephrine were administered through an interpleural catheter to eight dogs after tracheal extubation. Heart rate, respiratory rate, rectal temperature, hematocrit, plasma protein, blood gas, and pain score evaluations were recorded before surgery and 30 minutes, 1 hour, 2 hours, and 3 hours after extubation. Morphine caused significant decreases in blood pH and blood oxygen tensions, and significant increases in carbon dioxide tensions. Dogs treated with intercostal nerve blocks had no significant changes in these parameters, and dogs treated with interpleural bupivacaine had significant decreases in blood oxygen tension. All dogs had significant decreases in rectal temperature, and hypothermia was prolonged after morphine. Analgesia was initially adequate in most dogs, but some dogs in each treatment group had recurrence of pain and were treated with interpleural bupivacaine. One dog developed pneumothorax. Interpleural administration of bupivacaine produced analgesia equal to that produced by systemic administration of morphine or selective intercostal nerve block with bupivacaine. Bupivacaine was easily readministered through an interpleural catheter. Respiratory compromise was less in dogs treated with bupivacaine than in dogs treated with morphine. After intercostal thoracotomy, interpleural bupivacaine provided prolonged analgesia with fewer blood gas alterations than morphine. PMID- 1901185 TI - Selegiline: initial or adjunctive therapy of Parkinson's disease? AB - Parkinson's disease (PD) is a progressive neurologic motor disorder. Currently, levodopa/carbidopa is the standard mode of therapy for PD; however, it does not prevent progression of the disease. Selegiline (also known as deprenyl), is a selective irreversible monoamine oxidase type B inhibitor virtually devoid of the tyramine reaction at the recommended dosage of 10 mg/d. It is approved by the Food and Drug Administration for the adjunctive use in the management of patients with PD who are receiving levodopa/carbidopa and exhibit a "wearing off" effect of levodopa. Numerous clinical trials have been conducted evaluating selegiline's role in the treatment of PD. Preliminary evidence from the DATATOP trial suggests that selegiline may slow the progression of PD when used as initial therapy. However, final results of this trial and additional long-term controlled trials comparing selegiline to levodopa and placebo groups are necessary to further clarify selegiline's role in the treatment of PD. PMID- 1901184 TI - Schizophyllan augments development of immunoglobulin-secreting cells upon costimulation with Staphylococcus aureus Cowan I. PMID- 1901186 TI - Resistance to intravenous inoculation of Mycobacterium tuberculosis H37Rv in mice of different inbred strains following immunization with a leprosy vaccine based on Mycobacterium w. AB - Four strains of mice, namely Balb/c, C57BL/6 NCrl (Bcgs), C3H/He NCrl and CBA/N (Bcgr) were experimentally infected with Mycobacterium tuberculosis H37Rv (Trudeau Institute, Saranac Lake, NY) to induce sub-lethal infection. The level of infection was assessed by screening tuberculin reaction, pulmonary lesions, and viable units of mycobacteria recovered from the lung, spleen and liver. On prior immunization with 10(7) heat-killed suspension of Mycobacterium w, an anti leprosy vaccine currently under large scale human trials in India, protection was observed against tuberculosis in all the four strains of mice used in the study as assessed by significant reduction of both pulmonary lesions and viable units of mycobacteria recovered from different organs. In parallel experiments, live BCG was able to confer protection to mice of Bcgs strains but not to mice of the Bcgr strains. Results of these experiments suggest that a vaccine based on heat killed Mycobacterium w has the potential also to confer protection against tuberculosis in mice of genetic strains whose immune system is less triggered by intravenous injection of viable BCG. PMID- 1901188 TI - Hepatitis C: prevention and treatment. AB - Widespread screening of donor blood for hepatitis B led to the recognition that most cases of post-transfusion hepatitis were due to an agent or agents, collectively known as non-A, non-B. Until recently, the causative agent for non A, non-B hepatitis was unknown. In 1988, a new agent, hepatitis C virus, was identified. It is estimated that 150,000 new cases of hepatitis C occur each year and that one-half of patients with hepatitis C develop chronic liver disease. Hepatitis C is responsible for 15,000 new cases of cirrhosis annually. In 1990, an antibody assay was approved for commercial use. Widespread screening of donor blood with this assay should reduce the risk of transfusion-associated hepatitis C. For those patients already infected, antiviral therapy with alpha interferon may offer the chance of cure or significant palliation. PMID- 1901187 TI - Immunogenicity in adult males of a Neisseria meningitidis group B vaccine composed of polysaccharide complexed with outer membrane proteins. AB - Twenty five adult male volunteers were given a vaccine composed of the capsular B polysaccharide non-covalently complexed to serotype 6 outer membrane proteins (OMP) of Neisseria meningitidis. Subjects were divided into three dose groups receiving 50, 100 or 150 micrograms vaccine in aluminium hydroxide in each of three injections spaced 4 weeks apart. Systemic signs/symptoms considered clinically significant were recorded on 6% (4/70) of occasions and were succeeded by withdrawal of two volunteers from the study. Local injection site reactions, mostly mild to moderate, were reported after all vaccinations with one such reaction leading to a third volunteer withdrawing from the study. Geometric mean anti-B responses before immunization and 1 week after the third immunization (9 weeks) were 3.60 and 7.12 micrograms ml-1 in the 50 micrograms group (p less than 0.05) 2.05 and 12.19 micrograms ml-1 in the 100 micrograms group (p less than 0.001), and 3.68 and 14.20 micrograms ml-1 in the 150 micrograms group (p less than 0.001). The anti-B response was predominantly of the IgM isotype and persistence above prevaccination levels was evident for at least 12 months. Anti type 6 OMP responses were also evidenced with geometric mean multiplicative increases over prevaccination levels at 9 weeks and 6 months of 7.8 and 4.2 for the 50 micrograms group, 11.6 and 5.6 for the 100 micrograms group and 6.8 and 3.4 for the 150 micrograms group. The bulk of this response was of the IgG isotype. Passive protection of mice was achieved with both pre- and post vaccination (9 weeks; 100 and 150 micrograms groups) pools of sera.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1901190 TI - Multivessel coronary artery disease: a key predictor of short-term prognosis after reperfusion therapy for acute myocardial infarction. Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) Study Group. AB - Results of recent studies have suggested that routine cardiac catheterization may be unnecessary after reperfusion therapy for acute myocardial infarction. Therefore to better define the short-term prognostic value of early coronary angiography, and specifically the prognostic significance of multivessel coronary artery disease, the angiographic findings of 855 patients consecutively enrolled in five phases of the TAMI study were correlated with their in-hospital outcome. All patients received intravenous thrombolytic therapy (tissue plasminogen activator, urokinase, or both agents) and underwent cardiac catheterization within 90 minutes of the initiation of therapy. Multivessel disease, defined as the presence of greater than or equal to 75% luminal diameter stenosis in two or more major epicardial arteries, was documented in 236 patients. When compared with the group of patients without multivessel disease, this group had a higher prevalence of coronary risk factors and more frequently had a history of antecedent ischemic chest pain. Although the severity of the infarct zone dysfunction was similar in the two groups (-2.77 +/- 1.00 vs -2.50 +/- 1.09 SD/chord, p = NS), global left ventricular ejection fraction was lower in the group with multivessel disease (48.6 +/- 12.4% vs 51.8 +/- 10.6%, p less than 0.01). This was associated with a significant difference in the function of the noninfarct zone. Whereas this region was hyperkinetic in the group with minimal or single-vessel disease, it was hypocontractile or dyskinetic in those with multivessel disease (+0.66 +/- 1.53 vs -0.52 +/- 1.73 SD/chord, p = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1901189 TI - Submaximal exercise thallium-201 SPECT for assessment of interventional therapy in patients with acute myocardial infarction. AB - Submaximal thallium-201 stress testing has been shown to provide important diagnostic and prognostic information in patients with acute myocardial infarction. The purpose of this investigation was to evaluate the diagnostic value of early submaximal stress testing and thallium-201 single photon emission computed tomography (SPECT) after interventional therapy. Scintigraphic results from 56 patients with infarctions, who underwent acute thrombolytic therapy, angioplasty, or both, were compared with late (6 weeks) functional outcome as assessed by radionuclide ventriculography and with results of discharge coronary angiography. A linear correlation was found between the extent of thallium-201 SPECT perfusion defect and late ventricular function (r = 0.74, p less than 0.01). Forty-two percent of patients with large SPECT perfusion defects had normal left ventricular ejection fractions, suggesting an overestimation of infarct size by early imaging. Sensitivity and specificity of thallium-201 SPECT for detection of coronary artery stenosis in noninfarct territories was 57% and 46%, respectively, indicating limited diagnostic definition of extent of underlying coronary artery disease. Results of follow-up coronary angiography showed a significant relationship between the size of the initial perfusion defect and early restenosis or reocclusion of the infarct artery. Thus the extent of early thallium-201 perfusion defects correlates with late functional outcome but appears to overestimate the degree of injury. Submaximal thallium-201 stress testing allows only limited characterization of underlying coronary artery disease. Early assessment of infarct size may identify a patient population at high risk for reocclusion of the infarct artery. PMID- 1901191 TI - Cardiac tamponade following treatment with tissue plasminogen activator: an atypical hemodynamic response to pericardiocentesis. PMID- 1901192 TI - Nitrate tolerance in angina pectoris: effect of transdermal nitroglycerin with a four-hour nitrate-free interval. PMID- 1901193 TI - Obesity and weight loss alter serum polyunsaturated lipids in humans. AB - Serum omega 6 (n-6) fatty acids were assessed in 12 obese women during an outpatient very-low-calorie diet (VLCD). Ten subjects (S10) achieved a mean weight loss of 17 kg over 3-5 mo (initial weight-for-height 157%). Serum was obtained before (baseline) and monthly during the VLCD and from five of them (S5) after 2-3 mo of weight stability (refed) at 21 kg of loss. At baseline for S10, the serum phospholipid (PL) 20:4 omega 6 was 9.16 wt% and differed from normal (12.81 wt%) by P less than 0.0001, but cholesterol ester (CE) 20:4 omega 6 did not differ from normal. During 3 mo of VLCD, the S10 serum PL and CE 18:2 omega 6 fell (P less than 0.005 and 0.0001, respectively). Serum PL 20:4 omega 6 rose to normal during VLCD months 1-3 (P less than 0.01) while the serum CE 20:4 omega 6 rose above normal (P less than 0.0002). During the VLCD, S5 results paralleled S10. However when refed, S5 PL and CE 18:2 omega 6 and 20:4 omega 6 all reverted to baseline (PL 20:4 omega 6 below normal, P less than 0.001). Serum PL 20:4 omega 6 is low in moderate obesity, corrects to normal during a VLCD, but regresses to the predict abnormality after weight loss. PMID- 1901195 TI - Pteroylpolyglutamates in human milk. AB - Considerable variation exists in reported values for total folate content and the pteroylpolyglutamate (PteGlun) content of human milk. We investigated possible methodological sources of this variation. In two laboratories, milk folate content (with and without folate conjugase) was determined microbiologically. No differences in total milk folate or PteGlun (n greater than 3) content were found between laboratories. PteGlun was found to comprise a significant fraction of total milk folate (28%). Use of rennin did not alter total folate content nor the percent of PteGlun in human milk. Heating (121 degrees C for 5 min) increased folate concentrations (190%, P less than 0.0001), indicating that release of folate from binding protein is necessary for folate utilization by Lactobacillus casei. Although human milk folate conjugase, (FC) activity was approximately one twentieth that of plasma FC activity, it was not sufficient to autolyze endogenous PteGlun. Thus, microbiological protocols that do not use folate conjugase and do not release folate from binding proteins will seriously underestimate milk folate values. PMID- 1901194 TI - Hematological and biochemical effects of parenteral nutrition with medium-chain triglycerides: comparison with long-chain triglycerides. AB - Twenty-four malnourished patients requiring total parenteral nutrition were randomly assigned to receive a daily infusion of either Lipofundin MCT-LCT [a new lipid preparation containing medium-chain triglycerides (MCTs)], or Lipofundin S [a long-chain triglyceride (LCT) preparation] for 6-28 d. No adverse clinical effects were apparent in patients receiving the new emulsion. Hematological indices were unchanged. Plasma urea concentrations rose less on MCT-LCT than on LCT and the plasma bilirubin concentration was lower. Plasma ketones were higher immediately after the MCT-LCT infusion but not at other times. Triglyceride and fatty acid concentrations were similar. Insulin concentrations were higher on MCT LCT than on LCT. Daily nitrogen balance values were not significantly different between the two groups. Urinary carnitine excretion fell dramatically on both lipids. PMID- 1901196 TI - Acetate's metabolism, CO2 production, and the TCA cycle. PMID- 1901197 TI - Nutritional assessment of continuous ambulatory peritoneal dialysis patients: an international study. AB - We examined the nutritional status of 224 patients from six centers in Europe and North America to assess the incidence of protein-energy malnutrition. A "subjective nutritional assessment" was made, using 21 variables derived from history and clinical examination, or anthropometry and biochemistry. Eighteen patients (8%) were severely malnourished, 73 (32.6%) were mildly to moderately malnourished, and 133 (59.4%) did not show evidence for malnutrition. There was a higher incidence of mild to moderate malnutrition in diabetics than in nondiabetics. A statistical analysis identified 12 variables, seven objective and five subjective, that correlated with subjective nutritional assessment. Actual intercenter differences for the incidence of malnutrition were related to patient age, nutritional status at the commencement of continuous ambulatory peritoneal dialysis (CAPD), the length of time on CAPD, and residual renal function. Variables that were most frequently correlated with subjective nutritional assessment and with one another included plasma albumin, mid-arm muscle circumference (MAMC), weight loss, and the clinical judgement of muscle wasting and loss of subcutaneous fat. Loss of residual renal function correlated with muscle wasting and months on CAPD. Our data identified differences between the two sexes. In women there was a trend for more anorexia, greater weight loss from muscle wasting, and a larger decrease in albumin, whereas in men there was a more gradual decrease in nutritional status. Loss of residual renal function contributed to anorexia and symptoms of severe malnutrition. PMID- 1901198 TI - [Warning on techniques of propofol injection (Diprivan)]. PMID- 1901199 TI - Controlled trial of 2, 4, and 6 months of pyrazinamide in 6-month, three-times weekly regimens for smear-positive pulmonary tuberculosis, including an assessment of a combined preparation of isoniazid, rifampin, and pyrazinamide. Results at 30 months. Hong Kong Chest Service/British Medical Research Council. AB - In a study in Hong Kong 1,386 Chinese patients with sputum smear-positive pulmonary tuberculosis were allocated at random to four 6-month regimens of chemotherapy, all given three times weekly from the start and all containing isoniazid (H) and rifampin (R) throughout. Three contained streptomycin (S) for the first 4 months and pyrazinamide (Z) for 2 months (Z2), 4 months (Z4), or 6 months (Z6); the fourth contained pyrazinamide for 6 months but no streptomycin (Z6noS). Every dose of all four regimens was given under the direct supervision of clinic staff on a predominantly outpatient basis. During the later part of the intake patients were allocated at random to be given their HRZ either as a combined formulation (Rifater), each tablet containing 125 mg isoniazid, 100 mg rifampin, and 375 mg pyrazinamide, or as the three drugs separately. Among 892 assessable patients with drug-susceptible strains of tubercle bacilli pretreatment, bacteriologic failure during chemotherapy occurred in 4, all Z6noS (2% of 224; p less than 0.005 for the comparison with the S-containing regimens). During 30 months of follow-up after the end of chemotherapy, bacteriologic relapse occurred in 2 (3%) of 71 Z2, 2 (3%) of 72 Z4, 4 (6%) of 66 Z6, and 6 (9%) of 64 Z6noS patients allocated to Rifater, and in 4 (3%) of 149 Z2, 8 (6%) of 133 Z4, 2 (1%) of 142 Z6, and 6 (4%) of 135 Z6noS patients allocated to separate drugs. In the relapse rates there were no significant differences between the Rifater and separate drug regimens, the different durations of pyrazinamide, or the regimens with and without streptomycin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1901201 TI - The ventilatory and oxygen costs in the anesthetized rhesus monkey of inhaling drugs used in the therapy and diagnosis of asthma. AB - We examined in male Rhesus monkeys the effects on oxygen consumption (VO2), carbon dioxide production (VCO2), minute ventilation (VE), heart and respiratory rates, and functional residual capacity (FRC) of breathing normal saline (NS), salbutamol (albuterol), methacholine (MCh), sodium cromoglycate (SCG), epinephrine (adrenaline), and terbutaline in doses commonly prescribed to human infants and children. We studied 10 anesthetized and intubated monkeys with a mean age and weight of 6.0 yr and 9.1 kg, respectively. VO2 increased over control, by 46.5% after salbutamol (p less than 0.0005), 25% after methacholine (p less than 0.001), 13.2% after epinephrine (p less than 0.01), and 16% after terbutaline (p less than 0.001), but it did not increase after either SCG or NS. VE increased by 82% after MCh and salbutamol (p less than 0.001), less dramatically after epinephrine and terbutaline at 50.5 and 31.5% (p less than 0.02 and p less than 0.001), respectively, and not at all after SCG and NS. Heart rate response was greatest after salbutamol, and nodal and ventricular arrhythmias were noted in four of 10 monkeys after MCh challenge. FRC did not change significantly except after salbutamol, where there was a small rise of 1.8 ml/kg (p less than 0.05). PMID- 1901200 TI - Assessment of a daily combined preparation of isoniazid, rifampin, and pyrazinamide in a controlled trial of three 6-month regimens for smear-positive pulmonary tuberculosis. Singapore Tuberculosis Service/British Medical Research Council. AB - In a study in Singapore 310 patients with sputum smear-positive pulmonary tuberculosis were allocated at random to daily chemotherapy with streptomycin, isoniazid, rifampin, and pyrazinamide (1) for 2 months (2SHRZ), (2) for 1 month (1SHRZ), or (3) for 2 months without streptomycin (2HRZ). This was followed for all patients by three times weekly isoniazid and rifampin to a total duration of 6 months. During the initial period of daily chemotherapy the patients were also allocated at random to be given their HRZ either as a combined formulation (Rifater), each tablet containing 50 mg isoniazid, 120 mg rifampin, and 300 mg pyrazinamide, or as three separate drugs. During the Rifater versus separate drugs comparison the most common spontaneous complaints were of nausea and vomiting, reported by 8% of 155 patients receiving Rifater and 7% of 155 separate drugs. Other adverse effects were also reported in similar proportions in the two series. Among 271 patients with drug-susceptible strains of tubercle bacilli pretreatment there were no bacteriologic failures during chemotherapy. During 18 months of subsequent follow-up bacteriologic relapse occurred in 3 (7%) of 46 2SHRZ, 2 (5%) of 42 1SHRZ, and 3 (8%) of 40 2HRZ patients allocated to Rifater and in 0 of 47 2SHRZ, 1 (2%) of 46 1SHRZ, and 1 (2%) of 44 2HRZ patients allocated to separate drugs. There was no evidence of therapeutic benefit from continuing SHRZ administration beyond 1 month or from adding streptomycin to HRZ. The relapse rates were slightly higher in the Rifater series (p = 0.04). Further follow-up and results from other studies are therefore needed fully to assess the combined preparation. PMID- 1901202 TI - Eugenol causes oxidant-mediated edema in isolated perfused rabbit lungs. AB - Eugenol, an extract of cloves, has been associated with pulmonary edema when inhaled from commercially available clove cigarettes. We tested the hypothesis that eugenol directly causes lung edema through oxidant-mediated mechanisms by infusing eugenol (0.1 and 1.0 mM) into isolated rabbit lungs perfused with a cell free albumin and physiologic salt solution. We observed lung edema (1.0 mM) as demonstrated by increased lung weight gain and wet-to-dry lung weight ratios without alterations in mean pulmonary artery pressure. The oxygen metabolite scavengers catalase (1,000 U/ml) and dimethylthiourea (30 mM) attenuated lung edema. Instillation of dimethylurea, superoxide dismutase, or heat-inactivated catalase did not prevent lung edema formation. We conclude that eugenol causes lung edema in isolated lungs through oxidant-mediated mechanisms in the absence of circulating formed blood elements. Eugenol may be a valuable compound in the laboratory investigation of edemogenic disorders. PMID- 1901204 TI - A comparison of the roles of cefamandole and ceftriaxone in abdominal surgery. AB - In a prospective, randomized study, we compared the ability of ceftriaxone sodium (serum half-life, 8.0 hours) and cefamandole naftate and sodium carbonate (serum half-life, 0.8 hours) to prevent wound infection in 1238 patients undergoing abdominal surgery. Prophylaxis consisted of single-dose therapy at the time of induction of anesthesia, and treatment regimens contained ceftriaxone sodium, 1 g/d intravenously, or cefamandole naftate and sodium carbonate, 1 g intravenously every 6 hours. Except for low-risk biliary procedures, cephalosporin therapy was accompanied by the administration of metronidazole. No significant difference was noted in the incidence of wound infection, ie, 5.6% for the ceftriaxone group (95% confidence interval, 3.8% to 7.4%) and 6.9% for the cefamandole group (95% confidence interval, 4.9% to 8.9%). Single-dose prophylaxis with 1 g of cefamandole naftate and sodium carbonate was relatively inexpensive and provided a cost savings of 64%. When treatment was required, a 23% cost savings was associated with the use of a once-daily dose of 1 g of ceftriaxone sodium. PMID- 1901205 TI - Hypoprothrombinemia and hemorrhage in a surgical patient treated with cefotetan. AB - For 4 days before surgical repair of a diverticulitic colovesical fistula and for 6 days after, a 63-year-old man was treated with 2 g of intravenous cefotetan disodium every 12 hours for associated urosepsis with bacteremia. Postoperatively, the patient followed a diet of intravenous nutrition only. Uneventful convalescence was interrupted by signs of sudden major blood loss, accompanied by prolonged prothrombin time. After stabilization with packed red blood cells, fresh plasma, crystalloids, and parenteral vitamin K, laparotomy revealed a huge intra-abdominal clot, which was evacuated. This case illustrates the risk of unexpected hypoprothrombinemia and hemorrhage in a cefotetan-treated surgical patient who demonstrated none of the usual comorbid conditions generally described in patients with antibiotic-induced hypoprothrombinemia. Like cefamandole nafate, cefoperazone sodium, moxalactam disodium, and other cephalosporins containing the methylthiotetrazole side chain, cefotetan appears to pose an unusual risk of major bleeding. PMID- 1901203 TI - Methodologic issues in maintenance therapy clinical trials. AB - In the early 1980s, the National Institute of Mental Health supported a multicenter, randomized, controlled, clinical trial on unipolar and bipolar disorder to evaluate the comparative efficacies of lithium carbonate, imipramine hydrochloride, a lithium-imipramine combination, and placebo in preventing the recurrence of affective disorders. The objective of this report is to present a reanalysis of the relative efficacies of these treatments in patients with unipolar disorder to focus attention on general issues related to the design and conduct of maintenance therapy trials. We show that the earlier conclusions of that study that imipramine and the combination therapy are more effective than lithium and placebo in preventing the recurrence of depression in unipolar patients can be accounted for by alternative explanations that are a consequence of the design of the study. Our findings have important implications for the design, conduct, and interpretation of results of maintenance therapy clinical trials in general. PMID- 1901206 TI - Effect of spironolactone and phenobarbital administration on bilirubin glucuronidation in hepatic and extrahepatic rat microsomes. PMID- 1901207 TI - The differences in kinetics of rat and human DT diaphorase result in a differential sensitivity of derived cell lines to CB 1954 (5-(aziridin-1-yl)-2,4 dinitrobenzamide) AB - DT diaphorase (NAD(P)H dehydrogenase (quinone), EC 1.6.99.2) isolated from Walker 256 rat carcinoma cells can convert CB 1954 (5-(aziridin-1-yl)-2,4 dinitrobenzamide) to a cytotoxic DNA interstrand cross-linking agent. This is achieved by reduction of the 4-nitro group of CB 1954 to produce the hydroxylamino species, a bioactivation which accounts for the much greater sensitivity of Walker cells to CB 1954 when compared with other cells which are unable to carry out this reduction (Knox et al., Biochem Pharmacol 37: 4661-4669 and 4671-4677, 1988). As predicted from their measured DT diaphorase activities a number of rat hepatoma and hepatocyte cell lines were also shown to be sensitive to CB 1954. However, no CB 1954-sensitive cell lines of human origin were found, although levels of DT diaphorase similar to those in the sensitive rat cells were present in these cells. The human cells were as sensitive as rat cells to the active form of CB 1954 (5-(aziridin-1-yl)-4-hydroxyla mino-2-nitrobenzamide). DT diaphorase, purified to homogeneity from human Hep G2 cells, did metabolize CB 1954 to this 4-hydroxylamino product, but the rate of CB 1954 reduction and thus production of the cytotoxic product, was much lower than that of purified Walker enzyme (ratio of Kcat = 6.4). In addition, CB 1954 could be considered an inhibitor of, rather than a substrate for, the human form of DT diaphorase. The purified rat and human DT diaphorases possessed otherwise similar biochemical and molecular properties. These findings explain the decreased sensitivity towards CB 1954 of human cell lines when compared to rat cell lines. PMID- 1901208 TI - Differential potency of atropisomers of polychlorinated biphenyls on cytochrome P450 induction and uroporphyrin accumulation in the chick embryo hepatocyte culture. AB - The atropisomers of 2,2',3,4,6-pentachlorobiphenyl (PeCB), 2,2',3,4,4',6 hexachlorobiphenyl (HeCB), and 2,2',3,3',4,4',6,6'-octachlorobiphenyl (OCB) were studied in the chick embryo hepatocyte culture to determine if chirality plays a role in the recognition events associated with the induction of cytochromes P450 and the accumulation of uroporphyrin (URO). Concentration-related induction of cytochrome P450 content, ethoxyresorufin-O-deethylase (EROD) and benzphetamine N demethylase (BPDM) activities were measured. The rank order of potency for total cytochrome P450 induction was HeCB greater than OCB greater than or equal to PeCB. The (+)- and (-)-enantiomers of PeCB and OCB were of equal potencies as inducers of cytochromes P450, whereas the (+)-HeCB was greater than the (-)-HeCB. HeCB was a much more potent inducer of EROD activity than was either PeCB or OCB. EROD activity was induced to a much greater extent by the (+)-enantiomers of all compounds, with the (-)-enantiomers of PeCB and OCB being inactive. BPDM activity was induced by all three compounds in the order of OCB greater than or equal to HeCB greater than PeCB. The (-)-enantiomers were more potent inducers of BPDM activities than were the (+)-enantiomers, except for HeCB, in which the (+)- was more potent than the (-)-enantiomer. Analysis of porphyrin accumulation in cultures treated with delta-aminolevulinic acid revealed that (+)-HeCB caused the greatest percent URO accumulation, which also correlated with the greatest increase in EROD activity. All other enantiomers caused up to 47% URO accumulation, which did not correlate with an increase in EROD activity. PMID- 1901209 TI - [3H]acetazolamide binding to carbonic anhydrase in normal and transformed cells. AB - The binding of [3H]acetazolamide (AZ), a carbonic anhydrase (CA) inhibitor, to soluble and particulate forms of CA was investigated. Sources for the assays were purified CA II, adult rat cortical, oligodendrocyte and neuronal enriched preparations; cultured murine glial cells, rat C-6 glioma, rat hepatoma and human glioblastoma cells. CA enzyme activity in the same preparations was also assayed by following change in pH during incubation. A gel permeation chromatographic method was developed to assess [3H]AZ binding to soluble CA, while glass fiber filter vacuum filtration was used for particulate CA binding. Saturable specific binding of [3H]AZ to rat cortical soluble and particulate CA preparations was demonstrated. Computer-assisted data analysis estimated the binding parameters of [3H]AZ to soluble rat cortical CA to be Bmax = 0.38 +/- 0.13 pmol/mg protein and Kd = 34.7 +/- 17.5 nM. The rat cortical particulate fraction Bmax was 2.05 +/- 0.28 pmol/mg protein with a Kd of 107.1 +/- 24.2 nM. Purified bovine CA-II bound 1.15 +/- 0.19 pmol [3H]AZ/mg protein with a Kd of 54.0 +/- 3.4 nM. The pH optima for [3H]AZ binding to soluble and particulate CA was between 6.5 and 7.5. Binding was linear with respect to protein up to 1.0 mg/mL. The particulate fraction bound 3-4 times more [3H]ligand per unit protein than the soluble fraction. Interestingly, no detectable CA enzyme activity or [3H]AZ binding was observed in the soluble or particulate fractions of human glioblastoma, rat C-6 glioma or rat hepatoma cells. Binding of [3H]AZ to other soluble enzymes or proteins was negligible. In competition binding experiments, a rank order of inhibition of [3H]AZ binding to rat cortical CA by established CA inhibitors was: dichlorphenamide greater than acetazolamide greater than or equal to benzolamide greater than methazolamide greater than hydrochlorothiazide greater than or equal to sulfanilamide. [3H]AZ binding was not affected by other classes of pharmacologic characterizing agents. The binding of [3H]AZ to the CA enzyme molecule is highly specific and sensitive and may prove useful in vitro or in situ as a probe for this enzyme. PMID- 1901210 TI - Interactions of 5-hydroxytryptamine with oxidative enzymes. AB - Peroxidase (EC 1.11.1.7)/H2O2, ceruloplasmin (human type X)/O2, and tyrosinase (EC 1.14.18.1)/O2 all oxidized the indolic neurotransmitter 5-hydroxytryptamine (5-HT) in the physiological pH domain. Peroxidase/H2O2 oxidized 5-HT at pH values down to about 2.5. All oxidation reactions generated complex mixtures of products which included at least one known neurotoxin, tryptamine-4,5-dione. In general, the enzymatic oxidation pathways paralleled the in vitro electrochemical oxidation of 5-HT which has permitted suggestions to be made concerning the probable mechanisms of the enzyme-mediated reactions. PMID- 1901211 TI - Wernicke-Korsakoff syndrome of nonalcoholic origin. AB - We describe a patient who developed a severe loss of memory following intravenous feeding and intestinal surgery. The pattern of both anterograde and retrograde memory impairment and frontal pathology is shown to be comparable with that observed in patients with Wernicke-Korsakoff Syndrome of an alcoholic etiology. The data strengthen the view that the essential characteristics of the Wernicke Korsakoff Syndrome are not dependent on a prior history of chronic alcoholism. Implications of these data for the interpretation of alcoholic Wernicke-Korsakoff Syndrome are considered. PMID- 1901212 TI - Intracavitary irradiation of prostatic carcinoma by a high dose-rate afterloading technique. AB - A high dose-rate (60Co) afterloading technique was evaluated in a series of 73 patients with prostatic carcinoma stages I-IV. The intraurethral irradiation was combined with external pelvic radiotherapy. A minimum total dose of 78 Gy was delivered to the target volume. In a subgroup of patients estramustine (Estracyt) was given as adjuvant chemohormonal therapy during irradiation. The median follow up for the whole group was 63 months. The crude 5-year survival rate was 60% and the corrected survival rate 90%. Survival was related to the tumor grade. Local pelvic recurrences were recorded in 17.8%. 'Viable cells' in posttherapy aspiration biopsy were not associated with tumor recurrences or survival. Four patients (5%) had grade 3 late radiation reactions with urethral stricture or bladder fibrosis. Urinary tract infections and prior transurethral resections were not associated with a higher frequency of reactions. Concurrent estramustine therapy seemed to increase the frequency of both acute and chronic radiation reactions. Local control, recurrence, and survival were not affected by chemohormonal therapy. The use of tomography, magnetic resonance, and ultrasound as aids to computerized dosimetry may improve local dose distribution and reduce the irradiated volume. PMID- 1901213 TI - Quality assurance. DySSSy on the equator. PMID- 1901214 TI - Quality assurance. Norwegian standards. PMID- 1901215 TI - Quality assurance. Clinical directorates. PMID- 1901216 TI - Quality assurance. Going round in circles. PMID- 1901217 TI - Standard setting in practice. Interview by Chrissy Dunn. PMID- 1901218 TI - Substitution of lysine at position 104 or 240 of TEM-1pTZ18R beta-lactamase enhances the effect of serine-164 substitution on hydrolysis or affinity for cephalosporins and the monobactam aztreonam. AB - By site-directed mutagenesis, TEM-1 beta-lactamase was altered to contain single amino acid changes of E104K, R164S, and E240K, in addition to double changes of E104K/R164S or R164S/E240K and the triple change of E104K/R164S/E240K. Hydrolysis rates for cephaloridine and benzylpenicillin were lowered at least 1 order of magnitude for all enzymes containing R164S substitutions. All mutant enzymes exhibited increased kcat values for beta-lactam antibiotics containing an aminothiazole oxime side chain. Hydrolysis of ceftazidime was most affected, with kcat values increased 3-4 orders of magnitude in all enzymes with the substituted R164S moiety. Km values decreased for all substrates except ceftazidime in the enzymes with multiple mutations. Aztreonam was most affected, with Km values lowered 23-56-fold in the enzymes bearing multiple mutations. When the crystal structures of aztreonam and related monobactams were studied and projected into an active-site model of the PC1 beta-lactamase, it became apparent that the two lysine residues might serve equivalent roles by interacting with the carboxylate of the aminothiazole oxime side chain. Hydrogen-bonding interactions involving the oxime and N7 of the lysine, particularly Lys-104, may also be important in some antibiotics. Ser-164 apparently serves an indirect role, since it is somewhat distant from the active-site cleft. PMID- 1901219 TI - Effects of inhibitors of N-linked oligosaccharide processing on the secretion, stability, and activity of lecithin:cholesterol acyltransferase. AB - The structure and function of the carbohydrate moiety of human lecithin:cholesterol acyltransferase (LCAT) were determined by using several glycosidases in reaction with the isolated plasma protein or by using specific inhibitors of glycoprotein assembly with cultured cells secreting LCAT activity. Analysis of the plasma enzyme indicated that almost all of the large carbohydrate moiety of LCAT (approximately 25% w/w) was N-linked with part of the high-mannose and part of the complex type. This analysis was confirmed with metabolic inhibitors of carbohydrate processing by using CHO cells stably transfected with the human LCAT gene. Inhibitors of the subsequent processing of the N-linked high mannose chains formed by glucosidase activity were without effect on either the secretion rate or the catalytic activity of LCAT. The inhibition of catalytic activity by glucosidase inhibitors applied to both the phospholipase and the acyltransferase activities of LCAT. The reduction of the LCAT catalytic rate by terminal glycosidase inhibitors was without effect on apparent Km and did not affect enzyme stability. These data indicate an unusual specific role for high mannose carbohydrates in the catalytic mechanism of LCAT. PMID- 1901220 TI - 2-Aryl-1,3-thiazolidines as masked sulfhydryl agents for inhibition of melanogenesis. AB - As a part of an ongoing project aimed at developing new skin depigmenting agents, the ability of variously substituted 2-aryl-1,3-thiazolidines to inhibit melanogenesis in vitro was investigated. At 0.2 mM concentration 2-(2' hydroxyphenyl)-1,3-thiazolidine-4-carboxylic acid (Th2), as well as the descarboxy analog (Th1) and, to a lower extent, the 4'-hydroxy isomer (Th3) all proved capable of preventing the tyrosinase catalyzed conversion of 0.2 mM L tyrosine to melanin. Spectrophotometric monitoring of the reaction course in the presence of Th2 showed the initial formation of a yellow chromophore (lambda max 400 nm) which slowly decayed, being eventually replaced by a new absorption maximum centered at 305 nm. HPLC analysis of the final incubation mixture revealed the presence of a major product (lambda max 306 nm), ninhydrin and ferric chloride positive, which was isolated by gel filtration on Sephadex G-10 and was identified as beta-[7-(3-carboxy-5-hydroxy-3,4-dihydro-2H-1,4 benzothiazinyl)]al anine (DBA) by 1H-NMR spectroscopy. Attempts to isolate the intermediate with lambda max 400 nm were hampered by its marked instability under the usual chromatographic conditions. However, the nature of the chromophore, coupled with mechanistic considerations, suggested for the compound the Schiff base-containing structure 3,4-dihydroxy-5-S-(N salicylidenecysteinyl)phenylalanine (salcysdopa). This was substantiated by: (i) the formation of a zinc complex (lambda max 349 nm) analogous to that observed with the model Schiff base N-salicylidene leucine; and (ii) detection by 1H-NMR of a Schiff base resonance at delta 8.1 during the yellow chromophoric phase of the reaction. It was concluded that 1,3-thiazolidines inhibit melanin formation by a mechanism that involves the trapping of enzymically generated dopaquinone by the -SH containing Schiff base arising by cleavage of the thiazolidine ring. The salcysdopa adduct thus formed undergoes hydrolysis and subsequent ring closure to give eventually the colorless DBA. PMID- 1901221 TI - Comparative molecular topography of botulinum neurotoxins from Clostridium butyricum and Clostridium botulinum type E. AB - Production of botulinum-like neurotoxin by a non-Clostridium botulinum organism has profound implications in the epidemiology of the disease botulism. Molecular topography of the approximately 150 kDa neurotoxic protein produced by Clostridium butyricum (strain 5839) and its activation kinetics were examined and compared with a serologically related botulinum neurotoxin produced by C. botulinum type E to further characterize the butyricum neurotoxin. Botulinum neurotoxin was fully activated within 30 min of incubation with trypsin, whereas butyricum neurotoxin achieved maximum activation within 5 min of incubation. Molecular topography of the two neurotoxins was analyzed in terms of secondary structures and the surface accessibilities of the polypeptide domains containing aromatic amino acids. The secondary structure parameters of the butyricum neurotoxin (alpha-helix 22%, beta-sheet 41% and random coil 37%), as estimated from the far ultraviolet circular dichroic spectra, appeared similar to that of botulinum neurotoxin. (Singh, B.R. and DasGupta, B.R., (1989) Mol. Cell. Biochem. 86, 87). Second derivative ultraviolet spectral analysis revealed 37 and 41 Tyr residues exposed on the surface of butyricum and botulinum neurotoxins, respectively, suggesting a differential surface accessibility of polypeptide segments containing Tyr residues. Fluorescent Trp residues in both the botulinum type E and butyricum neurotoxins were in a relatively hydrophobic environment as indicated by the blue-shifted emission maxima (334 nm). About half of the fluorescent Trp residues of both proteins were accessible to acrylamide, a neutral fluorescence quencher, and appeared to be in a similar molecular environment. The ionic surface probe, I-, quenched the Trp fluorescence of botulinum significantly, but not that of butyricum neurotoxin. Thus, a considerable number of fluorescent Trp residues were apparently located on the surface of the botulinum, but not on that of the butyricum neurotoxin. Botulinum and butyricum neurotoxins, indistinguishable by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate, migrated differently in the absence of sodium dodecyl sulfate suggesting difference(s) in their surface charge distribution. These results provide the first report of the secondary and tertiary structure parameters of the neurotoxin produced by a non botulinum species and comparison of the molecular topography of the neurotoxin with the antigenically related botulinum neurotoxin type E. PMID- 1901222 TI - Biosynthesis of marsupial milk oligosaccharides: characterization and developmental changes of two galactosyltransferases in lactating mammary glands of the tammar wallaby, Macropus eugenii. AB - Tammar wallaby (Macropus eugenii) mammary glands contain two galactosyltransferases of which the first, 4 beta GalT, is a UDP-galactose:N acetylglucosaminyl beta 1----4-galactosyltransferase equivalent to the A protein of the lactose synthase of eutherian mammals. The second enzyme, 3 beta GalT, is a UDP-galactose:lactose beta 1----3-galactosyltransferase, not previously identified in mammary glands of any species, which catalyses the formation of Gal beta 1----3 Gal beta 1----4 Glc from lactose. The two enzyme activities, as well as the lactose synthase activity, have been characterised with respect to the effects of pH, apparent Km values, effects of bovine and tammar alpha lactalbumins, heat sensitivity and identity of products. Studies on the substrate specificity and heat sensitivity of the 3 beta GalT activity suggest that this enzyme may catalyse the beta-galactosylation of Gal beta 1----3Gal beta 1----4Glc as well as of lactose. The activity of the 3 beta GalT, unlike that of the 4 beta GalT, changes dramatically during the course of lactation in parallel with similar changes in the carbohydrate content of tammar milk. PMID- 1901223 TI - The genetics of plant lipids. PMID- 1901225 TI - Enhancement of the human plasma lipid transfer protein reaction by apolipoproteins. AB - Transfer of cholesteryl ester between triacylglycerol/phospholipid microemulsions catalyzed by human plasma lipid transfer protein was investigated with a pyrene containing analogue of which fluorescent properties depend on its concentration in the core of the microemulsions. The transfer of pyrene-cholesteryl ester between the emulsions was increased by the transfer protein linearly with its concentration, but maximally only to the extent of twice as much as spontaneous transfer in the given experimental conditions. When human apolipoproteins A-I or A-II are present in the reaction mixture enough to saturate the surface of the emulsion, the enhancement of the pyrene-cholesteryl ester transfer reaction by the transfer protein was 7.5-times more than in the absence of the apolipoproteins while the rate of spontaneous transfer was not affected significantly by the apolipoproteins. Bovine serum albumin did not have such an effect. Furthermore, the enhancement of the lipid transfer protein reaction by apolipoprotein A-I was linearly proportional to the percent saturation of the surface of the microemulsion with the apolipoprotein. PMID- 1901224 TI - The effect of dietary vitamin E and beta-carotene on oxidation processes in the rat testis. AB - The effects of dietary vitamin E and beta-carotene were studied on enzymes involved in arachidonic acid metabolism and other related enzymes in the rat testis. Groups of rats were fed various soybean oil-based semi purified diets. Group 1 was fed a vitamin E-supplemented diet (+E - beta); Group 2 was fed a beta carotene-supplemented diet (-E + beta); Group 3, the control group (-E - beta) was fed a vitamin E-deficient diet; and Group 4, the standard diet group (S), was fed vitamin E plus beta-carotene-standard diet. Soybean oxidized oil was added to the three diet groups - (+E - beta), (- E + beta) and (- E - beta), whereas the diet of S group contained non-oxidized oil. After 8 weeks rats were killed, blood and testis samples were collected for biochemical determinations. Vitamin E deficiency caused significant increase in testis thiobarbituric acid value and activities of testis NADPH oxidase, testis 15-lipoxygenase and in plasma pyruvate kinase. In contrast, significant decreases were observed in activity of testis prostaglandin synthetase, compared with antioxidant-supplemented diet groups. We also found a significant increase in 15-lipoxygenase activity in (- E + beta) diet group, compared with (- E - beta) diet group. Fatty acid analysis of testis parenchyma indicated decrease in palmitate (16:0) and arachidonate (20:4(n - 6)), and increase in oleate (18:1(n-6)) linoleate (18:2(n - 6)) and linolenate (18:3(n - 3)), when compared (-E - beta) diet group with vitamin E-supplemented diet groups. The results suggest that dietary vitamin E has a role in both enzymatic and non-enzymatic peroxidation of polyunsaturated fatty acids in the testis. PMID- 1901226 TI - Effect of luteinizing hormone releasing hormone pulse characteristics on comparative luteinizing hormone and follicle stimulating hormone secretion from superfused rat anterior pituitary cell cultures. AB - We have shown that 4 ng luteinizing hormone releasing hormone (LHRH) pulses induced significantly greater luteinizing hormone (LH) release from proestrous rat superfused anterior pituitary cells with no cycle related differences in follicle stimulating hormone (FSH). Current studies gave 8 ng LHRH in various pulse regimens to study amplitude, duration and frequency effects on LH and FSH secretion from estrous 0800, proestrous 1500 and proestrous 1900 cells. Regimen 1 gave 8 ng LHRH as a single bolus once/h; regimen 2 divided the 8 ng into 3 equal 'minipulses' given at 4 min intervals to extend duration; regimen 3 gave the 3 'minipulses' at 10 min intervals, thereby further extending duration: regimen 4 was the same as regimen 2, except that the 3 'minipulses' were given at a pulse frequency of 2 h rather than 1 h. In experiment 1, all four regimens were employed at proestrus 1900. FSH was significantly elevated by all 8 ng regimens as compared to 4 ng pulses; further, 8 ng divided into 3 equal 'minipulses' separated by 4 min at 1 and 3 h frequencies (regimens 2 and 4) resulted in FSH secretion that was significantly greater than with either a single 8 ng bolus (regimen 1) or when the 'minipulses' were separated by 10 min (regimen 3). In experiment 2, at proestrus 1500, FSH response to the second pulse of regimen 4 was significantly greater than in regimen 2; LH release was significantly suppressed at pulse 2 compared to regimen 2 accentuating divergent FSH secretion. At estrus 0800, FSH response to the second pulse of regimen 4 was significantly stimulated FSH at proestrus 1900, 1500 and estrus 0800, FSH divergence was most marked at proestrus 1500. These data indicate a potential role for hypothalamic LHRH secretory pattern in inducing divergent gonadotropin secretion in the rat. PMID- 1901227 TI - Effect of aspiration of the preovulatory follicle on luteinization, corpus luteum function, and peripheral plasma gonadotropin concentrations in the mare. AB - Follicular fluid from small- to medium-sized follicles has been shown to have an inhibiting effect on luteinization of granulosa cells in vitro. This study was conducted to investigate the effect of in vivo removal of follicular fluid on luteinization, peripheral gonadotropin concentrations, and ovulation of secondary follicles in the mare. Follicular fluid was aspirated from the preovulatory follicles of mares when the diameter of the follicle was 30-34 mm (Group A), 35 39 mm (Group B), or 40-44 mm (Group C). Mares in Group D served as controls and the preovulatory follicle was not aspirated. Mares in Group A had a significantly earlier rise in peripheral progesterone concentrations than did controls. There was no difference in duration of progesterone secretion or peak progesterone production between groups. LH and FSH values were significantly higher for mares in Groups A and B than for control mares. Mares in Group A tended to have a higher incidence of secondary ovulations than did mares in other groups. These data support the in vitro findings that follicular fluid from small- to medium sized follicles may contain a luteinization inhibitor, and indicate that presence of follicular fluid during the final days of follicular maturation is not essential for development of a normal CL. PMID- 1901228 TI - Possible role for arachidonic acid in the control of steroidogenesis in hen theca. AB - Studies were conducted to evaluate if arachidonic acid (C20:4) could function as a second messenger within theca cells from the second largest preovulatory (F2) follicle from the ovary of the domestic hen. Arachidonic acid stimulated basal progesterone and androstenedione production, but inhibited LH-induced androstenedione production. The stimulatory effects of arachidonic acid were not altered by either cyclooxygenase or lipoxygenase pathway inhibitors (indomethacin and nordihydroguaiaretic acid, respectively), but were blocked by agents that prevented mobilization and/or efflux of calcium (TMB-8 and verapamil). The inhibitory effects of arachidonic acid on LH-stimulated steroidogenesis were determined to occur both prior and subsequent to cAMP formation. Fifty and 100 microM arachidonic acid attenuated LH- (10 ng) and forskolin- (0.2 microM) induced cAMP levels, and decreased androstenedione and estradiol production following treatment with 8-bromo-cAMP. Phospholipase A2 (PLA2) and the calcium ionophore, A23187, stimulated the release of 3H from theca cells prelabeled with [3H]arachidonic acid, and both PLA2 and the closely related fatty acid, eicosatrienoic acid (C20:3), could replicate the inhibitory effects of arachidonic acid on LH-stimulated androstenedione production. Finally, neither indomethacin nor nordihydroguaiaretic acid blocked the inhibitory effects of arachidonic acid on LH-promoted androstenedione production. We conclude that arachidonic acid can be released within theca cells in response to physiologic (PLA2) and pharmacologic agents (A23187), and accordingly, that it may act directly as a second messenger to modulate both basal and LH-stimulated steroid production. PMID- 1901229 TI - Modulation of bovine luteal cell synthetic capacity by interferon-gamma. AB - Previous work from our laboratory has demonstrated that major histocompatibility complex (MHC) antigens are expressed on cultured bovine luteal cells following exposure to the T lymphocyte-derived cytokine, interferon-gamma (IFN-gamma). In light of these actions of IFN-gamma, it was of interest to investigate the effects of this cytokine on other aspects of luteal function. Therefore, bovine luteal cells were cultured for 7 days in the presence or absence of IFN-gamma, and luteal progesterone (P4), prostaglandin F2 alpha (PGF2 alpha), and 6-keto prostaglandin F1 alpha (6-keto-PGF1 alpha) production were evaluated. After a 24 h exposure to IFN-gamma (100 U), both PGF2 alpha and 6-keto-PGF1 alpha production were decreased approximately 50% (p less than 0.05). However, as time in culture progressed, IFN-gamma markedly increased the synthesis of both prostaglandins approximately 400% above controls (p less than 0.05). Stimulation of prostaglandin production by IFN-gamma was abrogated by the addition of exogenous P4. During the period of IFN-gamma-stimulated prostaglandin synthesis, LH stimulated P4 production was inhibited by IFN-gamma treatment. However, the suppression of P4 production by IFN-gamma was not mediated by the increase in prostaglandins since concomitant treatment with indomethacin did not reverse the inhibition of steroidogenesis. These results suggest that IFN-gamma, in addition to an indirect role in promoting immune response mechanisms, may also directly affect luteal function by enhancing luteal prostaglandin synthesis and by inhibiting luteal steroidogenesis. PMID- 1901230 TI - Poly(vinyl alcohol)-heparin hydrogels as sensor catheter membranes. AB - Poly(vinyl alcohol)-heparin hydrogels with varying water content were synthesized for use as sensor catheter membranes. Films were cast from aqueous mixtures of poly(vinyl alcohol) (PVA), a photosensitive cross-linker p-diazonium diphenyl amine polymer (PA), glutaraldehyde (GA) and heparin. After drying, the films were cross-linked by successive UV irradiation and heat treatment. To get an indication about the cross-linking density of the networks, the water content of the hydrogels was measured after equilibration in water. Hydrogels from PVA, PA, GA and heparin, with a water content of 35-95%, could be obtained if the components were dissolved in saline instead of water. The release of heparin from PVA-heparin or PVA-PA-heparin hydrogels was studied using different receiving phases. The cumulative amount of released heparin appeared to be dependent on the initial water content of the hydrogels and the composition of the receiving phase. For the PVA-PA-heparin hydrogels as well as the PVA-heparin hydrogels the cumulative amount of released heparin in water was about six times higher than in a Tris buffer. Using Tris buffer as receiving phase PVA-PA-heparin hydrogels with water contents of 53, 61 or 71% released heparin for at least 3 wk. The cumulative amount of released heparin increased with initial water content of these hydrogels. Recalcification times (RCT) of plasma exposed to PVA-PA-heparin hydrogels (water content 53%), which released heparin at a low rate (2 micrograms/cm2 per day), were markedly prolonged compared with the RCT values for PVA-PA hydrogels without heparin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1901231 TI - Reaction rate and collisional efficiency of the rhodopsin-transducin system in intact retinal rods. AB - A model of transducin activation is constructed from its partial reactions (formation of metarhodopsin II, association, and dissociation of the rhodopsin transducin complex). The kinetic equations of the model are solved both numerically and, for small photoactivation, analytically. From data on the partial reactions in vitro, rate and activation energy profile of amplified transducin turnover are modeled and compared with measured light-scattering signals of transducin activation in intact retinal rods. The data leave one free parameter, the rate of association between transducin and rhodopsin. Best fit is achieved for an activation energy of 35 kJ/mol, indicating lateral membrane diffusion of the proteins as its main determinant. The absolute value of the association rate is discussed in terms of the success of collisions to form the catalytic complex. It is greater than 30% for the intact retina and 10 times lower after permeabilization with staphylococcus aureus alpha-toxin. Dissociation rates for micromolar guanosinetriphosphale (GTP) (Kohl, B., and K. P. Hofmann, 1987. Biophys. J. 52:271-277) must be extrapolated linearly up to the millimolar range to explain the rapid transducin turnover in situ. This is interpreted by an unstable rhodopsin-transducin-GTP transient state. At the time of maximal turnover after a flash, the rate of activation is determined as 30, 120, 800, 2,500, and 4,000 activated transducins per photoactivated rhodopsin and second at 5, 10, 20, 30, 37 degrees C, respectively. PMID- 1901232 TI - Two-dimensional crystals of streptavidin on biotinylated lipid layers and their interactions with biotinylated macromolecules. AB - Streptavidin forms two-dimensional crystals when specifically bound to layers of biotinylated lipids at the air/water interface. The three-dimensional structure of streptavidin determined from the crystals by electron crystallography corresponds well with the structure determined by x-ray crystallography. Comparison of the electron and x-ray crystallographic structures reveals the occurrence of free biotin-binding sites on the surface of the two-dimensional crystals facing the aqueous solution. The free biotin-binding sites could be specifically labeled with biotinylated ferritin. The streptavidin/biotinylated lipid system may provide a general approach for the formation of two-dimensional crystals of biotinylated macromolecules. PMID- 1901233 TI - Human interleukin-9: genomic sequence, chromosomal location, and sequences essential for its expression in human T-cell leukemia virus (HTLV)-I-transformed human T cells. AB - We have isolated the genomic sequence of human interleukin-9 (IL-9) based on its sequence homology with a human IL-9 cDNA isolated from human T-cell leukemia virus (HTLV)-I-transformed T cells by expression cloning. The entire genomic sequence has been determined and the gene consists of five exons and four introns. The human IL-9 gene is mapped to the long arm of human chromosome 5 at band 5q31-32, a region found to be deleted in a number of patients with acquired 5q- abnormalities and hematologic disorders. Several blocks of transcriptional control sequences have been identified at the 5'-flanking region of the human IL 9 gene that may play an important role in the control of IL-9 gene expression. The 5'-regulatory region of the human IL-9 gene also contains sequences identified in the 5'-flanking regions of other cytokine genes mapped to the long arm of human chromosome 5, including IL-3, IL-4, IL-5, and granulocyte-macrophage colony-stimulating factor and other T-cell growth factor genes including IL-2 and IL-6. The IL-9 gene is constitutively expressed in the HTLV-I-transformed human T cells and the expression of IL-9 in these cells can be further induced by 12-O tetradecanoyl phorbol 13-acetate. Transient transfection analysis using the plasmid containing the 5'-flanking region of IL-9 gene upstream from the firefly luciferase ciferase report gene indicated that the 0.9-kb Smal-Sacl fragment of the IL-9 gene contains sequences required for the constitutive and activated expression of IL-9 gene in HTLV-I-transformed cells. These results will now allow us to study the regulatory mechanism of IL-9 gene expression in normal and leukemic human T cells. PMID- 1901235 TI - British AIDS funding: unfair distribution. PMID- 1901234 TI - Idiotypic cross-reactivity of immunoglobulins expressed in Waldenstrom's macroglobulinemia, chronic lymphocytic leukemia, and mantle zone lymphocytes of secondary B-cell follicles. AB - Monoclonal antibodies (MoAbs) specific for autoantibody-associated cross-reactive idiotypes (CRIs) of Waldenstrom's IgM react frequently with the surface Ig (slg) expressed by leukemia cells of patients with chronic lymphocytic leukemia (CLL). Evaluation of the molecular basis for this cross-reactivity indicates that such CRIs are encoded by conserved antibody variable region genes (V genes) that have undergone little or no somatic hypermutation. We find that such anti-CRI MoAbs stain a subpopulation of cells within the mantle zones surrounding the germinal centers of normal human tonsil. In contrast, MoAbs specific for variable region subgroup determinants react with cells in both the mantle zones and germinal centers of secondary B-cell follicles. To test whether mantle zone B cells not reactive with existing anti-CRI MoAbs may express slg bearing as-yet-unrecognized CRIs present on Igs produced by neoplastic cells of some patients with Waldenstrom's macroglobulinemia or CLL, we immunized mice with purified Waldenstrom's IgM that have been characterized for their variable region subgroups using subgroup-specific antisera raised against synthetic peptides. The supernatants of hybridomas generated from the splenocytes of immunized mice were screened for their ability to stain a subpopulation of mantle zone lymphocytes in human tonsil. With this approach, two new anti-CRI MoAbs were identified, designated OAK1 and VOH3. OAK1 binds to a CRI present on a subset of kappa light chains of the VK1 subgroup. VOH3 recognizes a CRI determinant(s) present on a subset of antibody heavy chains of the VH3 subgroup. Flow cytometric analyses demonstrated that OAK1 specifically binds leukemia cells from 5 to 20 patients (25%) with kappa light chain expressing CLL. In addition, VOH3 reacted with the leukemia cells from 1 of 17 (6%) patients tested. The success of these methods demonstrates that the variable regions of the Igs produced by mantle zone B cells share idiotypic determinants with Igs expressed in B-cell CLL (B-CLL) and Waldenstrom's macroglobulinemia. PMID- 1901236 TI - The role of the polyol pathway in diabetes mellitus. AB - The mechanism by which hyperglycaemia leads to diabetic complications has not been fully elucidated. Non-enzymatic glycosylation leads to considerable functional and structural alteration of proteins. Hyperglycaemia also induces changes in intracellular metabolites, particularly in the polyol pathway. Aldose reductase inhibitors, which block the polyol pathway, have been shown to prevent complications in animal models, and this provides the rationale for the large scale trials that are presently being conducted. PMID- 1901237 TI - [Synaptic contacts between SIF cells immunoreactive to cholecystokinin (CCK-8) in inferior mesenteric ganglia in the guinea-pig]. AB - Cell bodies and processes of SIF cells were found to be CCK-like immunoreactive within the mesenteric ganglion of the guinea-pig. Immunoreactivity was contained in granular vesicles, the labeling being chiefly associated with granules, about 100 nm in diameter. Asymmetric synaptic contacts between CCK-like immunoreactive SIF cells have been identified and a possible functional implication regarding intraganglionic connections for these SIF cells is discussed. PMID- 1901238 TI - [Psychophysical study of the chromatic discrimination in pigeons after lesions of thalamic nuclei Rotundus (RT) and Geniculatus Lateralis ventralis (GLv)]. AB - The discrimination threshold at 510 and 640 nm has been measured before and after the bilateral lesion with kainic acid of two main thalamic structures: the nucleus rotundus (Rt) and the nucleus geniculatus lateralis ventralis (GLv). When the lesion destroys the GLv and the lower part of the Rt, thresholds increase followed by a progressive recuperation. In contrast, when the Rt lesion is complete, and whether the GLv is touched or not, the threshold increase is both higher and does not come down to the pre-operatory levels even after 15 post operatory sessions. PMID- 1901239 TI - Modulation of human melanoma cells by interleukin-4 and in combination with gamma interferon or alpha-tumor necrosis factor. AB - Immune cytokines have been shown to play important roles in regulating immune cell functions. Interleukin-4 (IL4), originally described as a B-cell growth factor, is known to activate and differentiate other immune cells. IL4 has been given as an immunotherapeutic to tumor-bearing hosts. In this report, we set out to determine whether IL4 can directly modulate growth and expression of surface antigens on human melanoma cells. The effect of recombinant IL4 alone and in combination with recombinant gamma-interferon (IFN) or recombinant alpha-tumor necrosis factor (TNF) on melanoma cell lines was examined. IL4 significantly inhibited cell growth of all cell lines examined at 100-500 units/ml; but a dose dependent differential response to individual cell lines occurred. The effect of IL4 was augmented by combination with IFN or TNF. Melanoma-associated ganglioside antigens (GM3, GD3, GM2, GD2) and human leukocyte antigen class I and DR on the cell surface of melanoma cells were assessed by flow cytometry and/or a radiometric binding assay. IL4, IFN, or TNF alone enhanced human leukocyte antigen class I, DR, and beta 2-microglobulin antigen expression. IL4 alone and in combination with IFN or TNF increased the GM3/GD3 ratio expression. GD2 was enhanced significantly by IL4, IFN, and TNF. Pretreatment of melanoma with IL4 or with other cytokines prior to stimulation with peripheral blood lymphocytes significantly enhanced mixed lymphocyte tumor reaction activity as compared with non-treated melanoma used as stimulators. These studies demonstrate that IL4 alone or in combination with IFN and TNF can modulate melanoma growth activity and surface antigen expression to a more differentiated and immunogenic phenotype. PMID- 1901240 TI - Gonadal protection and fecundity rates in cyclophosphamide-treated rats. AB - Premature ovarian failure and reduced fecundity are well-documented consequences of cytotoxic chemotherapy used to treat patients with malignant diseases. To investigate the ability of different hormonal agents to block the effects of cyclophosphamide (CTX) on reproductive function, sexually mature female Long Evans rats were studied. Model development demonstrated that CTX, 6 mg/kg/day, 5 days/week for 3 weeks, was successful at inducing acyclicity and significantly reducing fertility and fecundity, with acceptable mortality, when compared to higher/lower dosages. Utilizing this model, animals were treated with CTX in combination with an inert vehicle, Lupron, 80 micrograms/kg every 24 h, Lupron, 40 micrograms/kg every 12 h, or s.c. progesterone capsules obtaining serum progesterone levels of 20-30 ng/ml. We concluded that progesterone was able to protect the gonad from the negative effects of CTX, maintaining fertility and fecundity rates not significantly different from those of untreated control animals. Lupron given every 12 h had a similar effect on fertility, but failed to protect fecundity (P less than 0.001). PMID- 1901241 TI - Similarity of expression of low molecular weight G proteins smg p21A and ras p21 in normal and malignant human tissues. AB - We prepared monoclonal antibodies specific for smg p21A, one of the low molecular weight GTP-binding proteins and possibly a suppressor molecule for ras p21. Two monoclonal antibodies (T22 and T212) reacted with smg p21A but not with Ki-ras p21, both of which were produced by Escherichia coli. These two clones detected an Mr 21,000 band in one-dimensional immunoblotting of extracts of a human pancreatic cancer cell line which was indistinguishable from a band detected by RASK-3, a monoclonal antibody specific for ras p21. However, T22 and T212 detected a single spot in two-dimensional immunoblotting that was clearly different from the three spots detected in the same cellular extracts by RASK-3. A series of normal and malignant human tissues were examined for the expression of smg p21A and ras p21 by immunohistochemical methods utilizing T22 and RASK-3. In essentially all tissues examined, both normal and malignant, smg p21A and ras p21 were expressed with great similarity. Expression of both molecules in all malignant tissues examined was coincident with that in normal tissues except that gastric cancer showed increased expression of the two molecules in comparison with normal gastric tissue. PMID- 1901242 TI - Single step selection of cis-diamminedichloroplatinum(II) resistant mutants from a human ovarian carcinoma cell line. AB - We have shown that cis diamminedichloroplatinum-(II) (DDP) resistant mutants can be isolated from the human ovarian carcinoma cell line A2780 using a single-step selection protocol with DDP. DDP resistant colonies were calculated to be present at a frequency of 1.7 x 10(-6)/viable cell using a fluctuation analysis. The mutational origin of these surviving colonies is inferred by the fact that their frequency is increased by treatment of the A2780 cells with the chemical mutagen ethyl methane-sulfonate, with a maximum frequency observed after a 3-day expression time. Independently isolated clones maintain, in the absence of selection, a DDP resistant phenotype up to 7-fold more resistant than the parental A2780 cells. The resistance modifiers aphidicolin and buthionine sulfoximine have no effect on the frequency of DDP resistant mutants. Therefore neither of these drugs appears to have an effect on increasing the sensitivity of DDP resistant mutants existing in a cell population prior to DDP exposure. PMID- 1901243 TI - Five-hour balloon inflation to resolve recurrent reocclusion during coronary angioplasty. AB - A 63-year-old male presented with an acute inferior myocardial infarction with initial clinical reperfusion following thrombolysis. Due to recurrent reocclusion, emergency catheterization was performed, demonstrating a 90% stenosis in the mid right coronary artery. Angioplasty was complicated by multiple reocclusions, ultimately requiring 5-h autoperfusion balloon inflation to maintain patency. PMID- 1901244 TI - Vasospasm in a coronary artery aneurysm. AB - Coronary artery aneurysms are not believed to have enough intact smooth muscle to generate significant vasoconstriction. A case is presented illustrating vasospasm of a large fusiform aneurysm of a right coronary artery during angioplasty. Pathophysiology of aneurysms is discussed. PMID- 1901245 TI - Interpretation of cardiac pathophysiology from pressure waveform analysis: III. Intraventricular pressure gradients. PMID- 1901246 TI - A methylsulfonyl metabolite of a polychlorinated biphenyl can serve as a ligand for liver fatty acid binding protein in rat intestinal mucosa. AB - When a 100,000 x g supernatant from rat intestinal mucosa was incubated with 4,4' bis([3H]methylsulfonyl)-2,2',5,5'-tetrachlorobiphenyl, [(CT3SO2)2TCB] a (CT3SO2)2TCB-protein complex was formed. The (CT3SO2)2TCB-protein complex was isolated and purified using gel filtration and ion-exchange chromatography. The protein portion of this complex was characterized to be liver fatty acid binding protein (L-FABP) by SDS-polyacrylamide gel electrophoresis and immunoblot analysis. No cross reactivity was observed in the immunoblot analysis between the purified protein and anti-heart or anti-intestinal fatty acid binding protein. (CT3SO2)2TCB was extractable from L-FABP and therefore not covalently bound to L FABP. PMID- 1901247 TI - Epoxidation of aflatoxin B1 by Aspergillus flavus microsomes in vitro: interaction with DNA and formation of aflatoxin B1-glutathione conjugate. AB - Metabolism of aflatoxin B1 (AFB1) by subcellular preparations of Aspergillus flavus is least understood. The results reported here have demonstrated for the first time the epoxidation of AFB1 and subsequent conjugation with glutathione (GSH). Microsomes prepared from toxigenic mycelia catalysed [3H]AFB1 to calf thymus DNA to a greater extent (approximately 2-fold) as compared to that of non toxigenic. The binding of [3H]AFB1 to exogenous and A. flavus nuclear DNA catalyzed by A. flavus microsomes was found to be comparable with that of mammalian extrahepatic tissue such as lung. Addition of phenobarbitone to the growing cultures resulted in 1.5-fold increase in [3H]AFB1-DNA binding mediated by microsomes prepared from either of the two strains. Tolnaftate, an inhibitor of aflatoxin synthesis enhanced the epoxidation rate in a dose-related manner. The binding of [3H]AFB1 to DNA catalyzed by A. flavus microsomes was significantly reduced (50% of control) upon addition of hamster liver cytosol, thereby substantiating the formation of the carcinogen adduct with DNA as reported in mammalian tissues. The metabolite formed by subcellular preparation of A. flavus was found to be AFB1-GSH having Rf value (6.5) similar to that obtained for mammalian liver preparations. PMID- 1901248 TI - Evidence of an adriamycin binding site in the secretory granules of the mast cell. AB - Adriamycin induced significant non-cytotoxic histamine release from rat peritoneal mast cells to which the drug showed a very high affinity. The relationship between adriamycin-induced exocytosis and its uptake by purified rat peritoneal mast cells was studied. Adriamycin induced histamine release and was highly concentrated in mast cells at 37 degrees C but not at 0 degrees C. However, if exocytosis was provoked by other secretagogues like compound 48/80, protamine, concanavalin A, and ionophore A23187, and cells were then treated with adriamycin at 0 degrees C, the concentrations of the antineoplastic drug significantly increased. Adriamycin binding to purified granular material was similar to that of intact cells treated at 37 degrees C, but was not modified by metabolic inhibitors, extremes of temperature (0 or 45 degrees C) or by the carboxylic ionophore monensin. On the contrary, sodium cromoglycate limited adriamycin binding to granular materials as well. In addition, sodium cromoglycate, but not monensin, displaced the antineoplastic drug from mast cells, even when added after adriamycin. We conclude that the high affinity of adriamycin for mast cells is ascribable to the externalization of a granular binding site, as a consequence of the exocytotic process. The experiments with sodium cromoglycate suggest that this binding site could be in common with the antiallergic drug. PMID- 1901249 TI - Immunocytochemical visualization of DNA adducts in mouse tissues and human white blood cells following treatment with benzo[a]pyrene or its diol epoxide. A quantitative approach. AB - The formation and stability of benzo[a]pyrene DNA adducts were studied in tissues of BALB/c mice exposed to benzo[a]pyrene (B[a]P). The DNA adducts were visualized with an immunocytochemical peroxidase staining technique using an antiserum specific for the major B[a]P-derived adduct in DNA [(+/-)trans-7,8-dihydroxy-anti 9,10-epoxy-7,8,9,10- tetrahydrobenzo[a]pyrene (BPDE-N2-dG)]. The nuclear staining density was measured by microdensitometry. When mice were treated with an increasing dose of B[a]P the nuclear staining increased in the tissues studied (lung, heart and kidney). A linear relationship was found between the immunocytochemical nuclear staining signal and the actual DNA adduct level in the lung as measured by 32P-postlabeling. Maximum adduct formation was found 5 days after a single i.p. injection of B[a]P. Adduct levels decreased gradually after 7 days, but even after 61 days a slight specific staining was still present, suggesting that not all adducts had disappeared at that time. As judged from the disappearance of [3H]thymidine from prelabeled DNA the loss of adducts from the lung was not a result of DNA repair but one of cell turnover. In human white blood cells B[a]P-derived adducts could be detected after in vitro incubation with the reactive metabolite of B[a]P (BPDE). Dose-response studies demonstrated a positive relationship between BPDE-DNA adduct formation, the immunocytochemical staining signal and the BPDE concentration in the culture medium. PMID- 1901250 TI - Bacterial formation of N-nitroso compounds from administered precursors in the rat stomach after omeprazole-induced achlorhydria. AB - The role of bacteria in catalysing intragastric formation of N nitrosothiazolidine-4-carboxylic acid and N-nitrosomorpholine was investigated in a rat model of omeprazole-induced achlorhydria. Omeprazole-treated rats gavaged with nitrosation-proficient bacteria were treated with nitrosamines and/or precursors and compared to control animals that received no omeprazole treatment/no bacteria. Rats given thiazolidine-4-carboxylic acid, nitrate and 10(11) cells of Escherichia coli, had a five times higher endogenous formation of N-nitrosothiazolidine-4-carboxylic acid as compared to controls. Endogenous formation of N-nitrosomorpholine was quantified by measuring its urinary metabolite N-nitroso-(2-hydroxyethyl)glycine; when rats were given morpholine and nitrite together with E. coli or Pseudomonas aeruginosa endogenous N nitrosomorpholine formation was increased approximately 2.5-fold as compared to controls. In the same experiment, a higher excretion of unchanged N nitrosomorpholine was also observed in omeprazole-treated rats receiving bacteria as compared to controls. Rats given morpholine, nitrate and E. coli or P. aeruginosa, excreted three times higher levels of N-nitrosomorpholine as compared to controls. These results conclusively demonstrate that nitrosation-proficient bacteria are capable of increasing intragastric formation of N nitrosothiazolidine-4-carboxylic acid and N-nitrosomorpholine. These N nitrosamines are formed from nitrate (or nitrite) and the respective amino precursor via reduction of nitrate into nitrite and bacterial nitrosation catalysis. PMID- 1901251 TI - Possible implication of arachidonic acid metabolism in the decrease of chemiluminescence production after exposure of murine peritoneal macrophages to diethylnitrosamine and tumour promoter, 12-O-tetradecanoylphorbol-13-acetate. AB - The effect of the carcinogen diethylnitrosamine (DEN) on prostaglandins (PGs), leukotrienes (LTs) and reactive oxygen intermediates production by murine peritoneal macrophages was assessed. In vitro exposure to DEN (0.8, 1.6 and 8 mM) resulted in a dose-dependent stimulation of the PGs and LTs generation by macrophages. DEN-exposed peritoneal macrophages demonstrated enhanced production of arachidonic acid (AA) metabolites following stimulation with 12-O tetradecanoylphorbol 13-acetate (TPA) as compared to macrophages stimulated with TPA alone. Studies of [3H]AA release from glycerolipids of prelabelled macrophages and of the distribution of AA metabolites between intra and extracellular compartments indicated that DEN induced de novo synthesis of AA metabolites. The stimulation of AA metabolism by DEN was decreased by H-7 and staurosporine, protein kinase C (PKC) inhibitors, and so could be dependent on PKC activation. The generation of PGs by macrophages after DEN exposure was also inhibited by indomethacin (cyclo-oxygenase inhibitor). DEN at high concentrations (1.6-16 mM) inhibited chemiluminescence production by peritoneal macrophages in a dose-dependent manner, triggered by tumour promoter TPA; lower concentrations (0.8 and 1.2 mM) increased this reactive oxygen intermediates dependent chemiluminescence production induced by TPA. The role of AA metabolism in the alteration of chemiluminescence production by murine peritoneal macrophages treated in vitro with DEN and triggered by TPA has been evaluated by using AA metabolism inhibitors. The stimulation of chemiluminescence by TPA was inhibited by the addition of phospholipase A2 (PLA2) inhibitor, 4-p-BPB; this metabolic inhibitor did not affect the decrease of chemiluminescence production induced by DEN. The cyclo-oxygenase (CO) inhibitor, indomethacin, reversed the inhibition of TPA-induced chemiluminescence caused by DEN. These results suggest that AA and/or a lipoxygenase product can potentiate the reactive oxygen intermediates production by macrophages stimulated by TPA. The CO pathway could be involved in the inhibition by DEN of the reactive oxygen intermediates generating enzyme system. It is suggested that this inhibition could be related to AA metabolites issued from the CO pathway or to DEN oxygenated metabolites issued from the co oxidation of the DEN by the PGs endoperoxide synthase. These results also raise the problem of macrophage dysfunction by chemical carcinogens and the implication of the CO pathway in this process. PMID- 1901252 TI - The skin tumorigenic and carcinogenic effects of different doses, numbers of dose fractions and concentrations of 7,12-dimethylbenz[a]anthracene in acetone applied on hairless mouse epidermis. Possible implications for human carcinogenesis. AB - Groups of hairless mice were painted with the carcinogen 7,12 dimethylbenz[a]anthracene (DMBA) dissolved in reagent-grade acetone in various doses, dose fractions and concentrations. The animals were examined once a week for an appropriate time period and skin tumors were registered and classified as tumors (all tumors appearing) and as malignant tumors. The results show that dividing a particular dose of DMBA into an increasing number of applications was the factor that had the greatest tumorigenic and carcinogenic effect. This was found for total doses of 100, approximately 50 and approximately 26 micrograms DMBA. Similarly, increasing the size of the dose increased the effect on the tumor and carcinoma crop, but to a less pronounced event than splitting the dose into several fractions. The most striking of these effects was that a single dose of 51.2 micrograms DMBA gave a tumor rate of approximately 40%, whereas the same dose divided into 50 doses of 1 microgram gave a tumor rate of almost 100%. The final tumor yield increased from approximately 45 tumours per 32 animals after a single dose of 51.2 micrograms DMBA to approximately 250 tumors per 32 animals after 50 applications of 1 microgram DMBA. The final number of carcinomas per 32 animals was one carcinoma after a single application of 51.2 micrograms DMBA, and 40 carcinomas after 50 applications of 1 microgram DMBA. The paper includes a discussion on how these findings may be explained in terms of the complicated series of events that constitutes carcinogenesis. If it is biologically plausible to regard agents for which there is sufficient evidence for carcinogenicity in experimental animals as representing a carcinogenic risk to humans, then it may also be plausible and prudent to infer that the dose schedule that represents the highest tumorigenic hazard for mouse skin may generally also be the dose schedule that involves the highest risk for humans. Thus, repeated exposure to small doses may be the most hazardous situation. This is unfortunately the way many human beings are exposed to cigarette smoke, sunshine and carcinogens in food, water, air and at the work place. As shown in a previous paper, an increasing time interval between each dose may also increase the risk. PMID- 1901253 TI - Lack of significant modulation of the formation and removal of platinum-DNA adducts by aphidicolin glycinate in two logarithmically-growing ovarian tumour cell lines in vitro. AB - Two recently established human ovarian carcinoma cell lines (JA-T and TR175) have been used to study the effects of aphidicolin glycinate (APG), a specific competitive inhibitor of DNA polymerase alpha (Ikegani et al. (1978) Nature, 275, 458-460), on the formation and removal of four platinum-DNA adducts. Logarithmically-growing cells were exposed to cis-diamminedichloroplatinum (II) (cisplatin) (10 micrograms, 33.4 microM) in the presence or absence of APG (5 or 50 micrograms/ml, 11.6 or 116 microM). Platinum-DNA adducts were quantitated using a competitive ELISA technique. No differences were observed between the initial levels of total DNA platination and of specific DNA adducts formed in the presence or absence of APG in either cell line. Following 18 h posttreatment incubation both lines showed some ability to remove each of the three main platinum-DNA lesions (Pt-GMP, Pt-AG and Pt-GG). However, the levels of these specific DNA adducts decreased over this time period, by similar rates with or without APG addition. It was also shown that the APG concentrations used had minimal inhibitory effects alone on growth or DNA synthesis during this 18 h posttreatment incubation period. Furthermore its addition did not significantly modify cisplatin-induced cytotoxicity, as judged by inhibition of growth or DNA synthesis over this time period. We therefore conclude that under these experimental conditions APG does not modulate 'repair' of cisplatin-induced DNA damage in logarithmically-growing cultures of these two apparently 'repair proficient' human ovarian tumour cell lines. PMID- 1901254 TI - Segmental vascular resistance in isolated perfused rat lungs. Influence of vasomotor tone and cyclooxygenase and lipoxygenase inhibition. AB - We have determined the profile of pressures in isolated perfused lungs of adult rats and investigated the influence of vasomotor tone and cyclooxygenase and lipoxygenase inhibition on total and segmental vascular resistance. We isolated and blood-perfused lungs of 30 rats (480 +/- 21 g). Group 1 (n = 7) was untreated, group 2 (n = 8) was paralyzed with papaverine, group 3 (n = 11) was treated with indomethacin, and group 4 (n = 4) was treated with indomethacin and U60257, a putative lipoxygenase inhibitor. Blood flow was adjusted initially to raise pulmonary artery pressure to approximately 15 cm H2O and then held constant. Airway and left atrial pressures were held constant at 7 and 8 cm H2O, respectively (zone 3 conditions). In all lungs, we measured pressures in subpleural 20-50-microns-diameter arterioles and venules using the micropuncture servonull technique. Thus, the pulmonary circulation was partitioned into three segments: arteries, microvessels, and veins. In group 1 lungs, arteries presented the largest fractional resistance to flow at 46% of total resistance, with microvessels and veins contributing 34% and 20%, respectively. In group 2 lungs that had no vasomotor tone, total vascular resistance was approximately 27% lower than in group 1 lungs, mainly due to a lower resistance in veins. In indomethacin treated lungs (group 3) and indomethacin and U60257-treated lungs (group 4), total and segmental vascular resistance was not significantly different from untreated lungs (group 1). We conclude that in isolated perfused rat lungs, arteries are the predominant site of resistance to blood flow.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1901255 TI - Inhibitors of cytochrome P-450 attenuate the myogenic response of dog renal arcuate arteries. AB - The role of cytochrome P-450 in the myogenic response of isolated, perfused renal arcuate arteries of dogs to elevations in transmural pressure was examined. The phospholipase A2 inhibitor oleyloxyethylphosphorylcholine (1 and 10 microM) inhibited the greater than threefold increase in active wall tension in these arteries after an elevation in perfusion pressure from 80 to 160 mm Hg. Inhibition of cyclooxygenase activity with indomethacin (1 or 10 microM) had no effect on this response. The cytochrome P-450 inhibitors ketoconazole (10 and 100 microM) and beta-diethyl-aminoethyldiphenylpropylacetate (SKF 525A, 10 and 100 microM) also inhibited the myogenic response. At a pressure of 160 mm Hg, SKF 525A (10 microM) and ketoconazole (100 microM) reduced active wall tension in renal arteries by approximately 70%. Partial inhibition of the myogenic response was obtained after perfusion of the vessels with mechanism-based inhibitors of P 450, 1-aminobenzotriazole (75 microM) and 12-hydroxy-16-heptadecynoic acid (20 microM). The thromboxane receptor antagonist SQ 29,548 (1 or 10 microM) had no effect on the pressure-induced increase in active wall tension in renal arteries. Arachidonic acid (50 microM) constricted isolated perfused renal arteries and potentiated the myogenic response in the presence of indomethacin. This response was completely reversed by ketoconazole (100 microM) or SKF 525A (100 microM). Microsomes (1 mg/ml) prepared from small renal arteries (200-500 microns) and incubated with [1-14C]arachidonic acid (0.5 mu Ci, 50 microM) produced a metabolite that coeluted with 20-hydroxyeicosatetraenoic acid (20-HETE) during reversed-phase high-performance liquid chromatography. The formation of this product was inhibited by both ketoconazole and SKF 525A at concentrations of 10 and 100 microM. These results are consistent with the involvement of the vasoconstrictor 20-HETE and other cytochrome P-450 metabolites of endogenous fatty acids in the myogenic response. PMID- 1901256 TI - Cytochrome P-450-dependent vasodilator responses to arachidonic acid in the isolated, perfused kidney of the rat. AB - Pretreatment of phenylephrine (0.5 microM)-preconstricted, isolated perfused kidneys of the male rat with indomethacin (2.8 microM) or BM 13.177 (20 microM) abolished the vasoconstrictor response to arachidonic acid (AA), uncovering a vasodilator response. BW 755C (25 microM), a dual cyclooxygenase/lipoxygenase inhibitor, did not modify the vasodilator effect of AA, whereas 5,8,11,14 eicosatetraynoic acid (10 microM), which blocks all pathways of AA metabolism, abolished AA-induced vasodilation, thus suggesting the involvement of nonlipoxygenase AA metabolites. Clotrimazole (0.7 microM) and 7-ethoxyresorufin (1 microM), both considered to be specific inhibitors of the cytochrome P-450 monooxygenase enzymes, inhibited the vasodilator effect, suggesting that AA induced renal vasodilation is mediated by one or more cytochrome P-450-derived AA metabolites. None of these interventions affected the vasodilator responses to acetylcholine (100 ng) and nitroprusside (1 microgram). Denudation of the endothelium with CHAPS (10 mg/l) reduced the vasodilator responses to AA, suggesting a requirement of an intact endothelium, whereas inhibition of guanylate cyclase with methylene blue (10(-4) M) was without effect, suggesting that cGMP was not involved in the vasodilator response to AA. The AA-induced renal vasodilation was accompanied by the generation of biologically active material or materials released into the renal effluent, which relaxed endothelium intact and endothelium-denuded rings of isolated aorta and mesenteric and celiac arteries of the rabbit. These results suggest that in the rat kidney, AA is metabolized by endothelial cytochrome P-450-dependent enzymes to vasodilator metabolites. PMID- 1901257 TI - Cardiovascular responses as behavior. AB - Exercise is a ubiquitous, biologically and clinically significant behavior. Although the somatomotor responses are generally regarded as "behavior," the cardiovascular adjustments that accompany these responses are generally considered to be reflexes that are elicited by neurally mediated stimuli and metabolites arising from working muscles. We report experimental evidence that monkeys can be trained to exercise, to slow heart rate, and to combine these two skills. Furthermore, some animals will emit more physical work at slower heart rates (at comparable levels of cardiac output) and lower left ventricular work during the combined condition relative to an exercise-only condition. Thus, these findings show that the cardiovascular and somatomotor responses of exercise can be dissociated and that both sets of responses should be considered behaviors. Also included are results that show these animals can perform these behaviors during sympathetic or vagal blockade. These findings are further evidence that the cardiovascular adjustments to exercise are, in part, learned behaviors because they show that the behavior--attenuation of the tachycardia of exercise- is not a reflex that is specifically tied to any neuroeffector system; rather, this behavior is emitted to achieve a contingent reward, and the nervous system will use whatever mechanisms are available to attain that consequence. PMID- 1901258 TI - Rheumatoid factors and complex formation. The role of light-chain framework sequences and glycosylation. AB - New information regarding rheumatoid factors (RFs) indicates that the RFs synthesized in synovium and lymphoid tissues of patients with rheumatoid arthritis (RA) are different from monoclonal and nonspecific RFs associated with other inflammatory states. The characteristics of RF associated with RA are as follows. They are of all Ig isotypes (not just IgM), indicating T-cell participation in antibody maturation. They have higher avidity for human IgG than for rabbit IgG. They use the human germline heavy-chain variable region (VH) gene VHIII more frequently than other VH genes, and light chains from multiple families. (In contrast, monoclonal RFs use predominantly VH1 and very commonly the V kappa IIIb germline gene HUMkv325). RA IgG is somatically mutated. (In contrast, monoclonal RFs use unmutated germline Ig genes). This suggests they are matured by stimulation either with specific antigens or other activation signals such as cytokines. They are abnormally glycosylated. In general, during periods of disease activity in adult and juvenile RA, a galactose is missing from the Fc of the IgG molecule, leaving an empty "pocket" between the C gamma 2 domains of heavy chains. The IgG RFs self-associate. This may result at least in part when galactose on the F(ab')2 portion of one IgG molecule fills the empty pocket in the Fc of another Ig molecule. Self-association forms immune complexes capable of fixing complement and probably of causing joint damage and vasculitis. PMID- 1901259 TI - Imaging of the intensive care unit patient. AB - Despite advances in "high tech," it is anticipated that plain chest film radiography will continue to play a significant role in the management of patients in the ICU. Digital radiography will most likely displace conventional approaches. As demonstrated throughout this article, CT has played an increasingly important role in the evaluation of the critically ill patient. The results are especially impressive, because most were obtained on earlier generation CT machines, which are now totally outdated. Newer scanners have many technical improvements, including rapid scanning, which permits breathholding, and thin-section scanning, which has been discussed in great detail throughout this volume. Whether MR imaging will play an important role in ICU care remains to be determined. PMID- 1901260 TI - Amoxicillin-clavulanic acid for treating drug-resistant Mycobacterium tuberculosis. AB - This report describes two patients with multidrug resistant tuberculosis who were successfully treated with the addition of amoxicillin-clavulanic acid to second line drugs. Mycobacterium tuberculosis possesses a beta-lactamase contributing to its resistance to beta-lactam antibiotics. The combination of clavulanic acid, a beta-lactamase inhibitor, and amoxicillin has been shown bactericidal for M tuberculosis in vitro. These data suggest that resistant tuberculosis may warrant a trial of treatment including amoxicillin-clavulanic acid. PMID- 1901261 TI - Tuberculous pleural effusion. Twenty-year experience. AB - We reviewed the records of 1,738 cases of tuberculosis seen during the period from 1968 to 1988 in Mobile, Alabama. Seventy cases of tuberculous pleural effusion were identified and constituted 4.9 percent of all disease due to Mycobacterium tuberculosis during this period. Tuberculous pleural effusion was diagnosed if the patient had M tuberculosis cultured from sputum, pleura, or pleural fluid and had a roentgenographic pleural effusion without an alternative explanation for the presence of the effusion. The diagnosis of tuberculous pleural effusion was made in the absence of a positive culture if the patient had an undiagnosed lymphocytic exudative pleural effusion and all clinical and roentgenographic abnormalities resolved on antimycobacterial chemotherapy. The mean age of all patients was 47 +/- 18.4 years. The 70 cases were evenly divided between 35 that were accompanied by roentgenographic pulmonary parenchymal infiltrates and 35 that occurred in the absence of parenchymal infiltrates. We conclude that cultures of all potentially diagnostic specimens (sputum, pleural fluid, and pleura) and an intermediate-strength skin test, are sensitive tests for the diagnosis of tuberculous pleural effusion. In addition, the age of patients with tuberculous pleural effusion appears to be increasing. PMID- 1901263 TI - Expression of the disconnected gene during development of Drosophila melanogaster. AB - Proper development of the larval visual nerve, Bolwig's nerve, of Drosophila melanogaster requires the wild type function of the disconnected (disco) gene. In disco mutants, the nerve does not make stable connections with its targets in the larval brain. We have begun to explore the role of disco in the formation of the nervous system by examining the distribution of disco mRNA and protein in embryos and third instar larvae using in situ hybridization and antibody staining respectively. No differences between the distribution patterns of the two products are detected; disco is expressed in many tissues including both neural and non-neural cells. Many of the cells which express disco undergo extensive movement during development as they participate in major morphogenetic movements. Antibody staining shows that the protein is found in the cell nucleus. Products of the disco gene are detected in cells near the terminus of the growing Bolwig's nerve. In embryos homozygous for either of two mutant alleles of disco, the disco protein is absent near the nerve terminus, although protein distribution elsewhere is indistinguishable from wild type. PMID- 1901262 TI - Isolation and characterization of the disconnected gene of Drosophila melanogaster. AB - Mutations in the disco (disconnected) gene prevent the establishment of stable connections between the larval optic nerves, the Bolwig's nerves, and their target cells in the brain during embryonic development. The failure of this initial connection is associated with aberrant development of the optic lobes which are largely degenerate in the mutant adult fly. In order to understand the role of disco in establishing this connection, we isolated and characterized the disco gene. A 22 kb DNA fragment can completely rescue the mutant phenotype. A single transcript, 2.9 kb in length, is found in this region and is expressed throughout development of the fly. We determined the nucleotide sequence of the disco gene to be unique when compared with sequences in a number of databases. The predicted amino acid sequence contains a region with similarity to the consensus established for the zinc finger motif. Mobilization of a P-element inserted near the gene resulted in the deletion of the 5' end of the gene and produced flies indistinguishable from those carrying the disco allele. PMID- 1901264 TI - Development of the CD4 and CD8 lineage of T cells: instruction versus selection. AB - T cells bearing the alpha beta T cell receptor (TCR) can be divided into CD4+8- and CD4-8+ subsets which develop in the thymus from CD4+8+ precursors. The commitment to the CD4 and CD8 lineage depends on the binding of the alpha beta TCR to thymic major histocompatibility complex (MHC) coded class II and class I molecules, respectively. In an instructive model of lineage commitment, the binding of the alpha beta TCR, for instance to class I MHC molecules, would generate a specific signal instructing the CD4+8+ precursors to switch off the expression of the CD4 gene. In a selective model, the initial commitment, i.e. switching off the expression of either the CD4 or the CD8 gene would be a stochastic event which is then followed by a selective step rescuing only CD4+ class II and CD8+ class I specific T cells while CD4+ class I and CD8+ class II specific cells would have a very short lifespan. The selective model predicts that a CD8 transgene which is expressed in all immature and mature T cells should rescue CD4+ class I MHC specific T cells from cell death. We have performed experiments in CD8 transgenic mice which fail to support a selective model and we present data which show that the binding of the alpha beta TCR to thymic class I MHC molecules results in up-regulation of the TCR in the CD4+8+ population. Therefore, these experiments are consistent with an instructive model of lineage commitment. PMID- 1901265 TI - Cytoplasmic activation of GAF, an IFN-gamma-regulated DNA-binding factor. AB - We have investigated events following treatment of cells with interferon-gamma (IFN-gamma) that lead to the immediate transcriptional activation of an inducible gene. A gamma-interferon activation factor (GAF) was activated in the cytoplasm of human fibroblasts immediately after IFN-gamma treatment and bound to a newly identified target DNA sequence, the gamma-interferon activation site (GAS). The time course of activation of GAF was different in fibroblasts and HeLa cells and correlated well with IFN-gamma-induced transcriptional activation in both cell types. IFN-gamma-dependent activation of GAF also occurred in enucleated cells (cytoplasts), showing that an inactive cytoplasmic precursor is converted to the active factor. These findings support the concept that ligand-specific signals originating at the cell surface are transmitted through latent cytoplasmic proteins which are activated to bind specific DNA sites and then move to the nucleus to activate the transcription of specific sets of genes. PMID- 1901266 TI - Expression and biological effects of high levels of serum IgE in epsilon heavy chain transgenic mice. AB - We have generated and examined transgenic mice carrying a rearranged immunoglobulin transgene coding for the heavy chain of an IgE antibody. These mice produce the secreted form of the recombinant epsilon heavy chain. Serum IgE levels were increased at least 100-fold over control values. Transgenic epsilon mRNA was detected in spleen and thymus, not in liver and heart. Transgenic epsilon production in vitro was slightly up-regulated by T cells, but not affected by interleukin 4 in vitro or Nippostrongylus infestation in vivo. The B cell and T cell compartments and antigen-specific IgE, IgG1 and IgM responses as well as the increase in endogenous IgE after Nippostrongylus infestation in transgenic mice were normal. These data indicate that the presence of high levels of transgenic IgE did not induce class-specific suppressive mechanisms. Transgenic IgE bound to Fc epsilon receptor type I and Fc epsilon receptor type II and mediated histamine release from mast cells in vitro and an allergic skin reaction in vivo. It inhibited an ovalbumin-specific skin reaction in ovalbumin immunized transgenic mice only during the initial phases of the immune response. This result has a bearing on the feasibility of immune therapy of allergic diseases with substances that block binding of IgE to its receptors. PMID- 1901267 TI - Contribution of the VH11 gene family to mitogen-responsive B cell repertoire in C57BL/6 mice. AB - The contribution of VH11 gene family to the development of the primary B cell repertoire has been studied by analyzing 1.8 x 10(4) mitogen induced B lymphocyte colonies. The data demonstrate that VH11 family is predominantly expressed among neonatal splenic as well as adult peritoneal B cell colonies, both rich in Ly-1+ B cells. VH11 gene family expression among B splenocytes decreases during ontogeny and VH11 family pairs stochastically with different V kappa families among mitogen-activated neonatal B cell colonies, which are representative of an antigen unselected B cell repertoire. Thus, an increased VH11 expression among peritoneal and neonatal B cells points towards its biased expression among Ly-1+ B lymphocytes. The restricted V gene rearrangements and VH11-V kappa 9 pairing observed among anti-bromelain-treated mouse red blood cells autoantibodies are likely to be an outcome of both intrinsic gene recombination processes per se as well as selection by an autoantigen and/or local selective environmental factors. PMID- 1901268 TI - Lack of anti-DNA precursors in lambda chain-bearing B lymphocytes in (NZB x NZW)F1 mice. Evidence for the contribution of V kappa genes to anti-DNA specificity. AB - We have analyzed by the limiting dilution assay on spleen cells from (NZB x NZW)F1 hybrid mice the repertoire of lipopolysaccharide-responsive murine kappa- and lambda 1-secreting B cells committed to the production of anti-DNA autoantibodies to determine the contribution of the heavy and light chains to anti-DNA specificities. Our results demonstrated that anti-DNA precursors were predominantly found in the kappa-secreting B cell population, but not in lambda 1 secreting B cells, while anti-hapten, dinitrophenyl, and anti-tetanus toxoid activities were distributed fairly well in both populations of B cells. This suggests that the V kappa gene segments are critically involved in the generation of anti-DNA specificities, and that at least at the germ-line gene level, the heavy chain V region genes by themselves are not able to confer the anti-DNA autoreactivity. PMID- 1901269 TI - Plasmodium berghei: lactic acidosis and hypoglycaemia in a rodent model of severe malaria; effects of glucose, quinine, and dichloroacetate. AB - Fulminant malaria infections are characterised by hypoglycaemia and potentially lethal lactic acidosis. In young adult Wistar rats (n = 26) infected with Plasmodium berghei (ANKA strain), hyperparasitaemia (greater than 50%), anaemia (PCV 19.6 +/- 5.3%; mean +/- SD) hypoglycaemia (1.04 +/- 0.74 mmol/litre), hyperlactataemia (13.2 +/- 2.20 mmol/litre), hyperpyruvicaemia (0.51 +/- 0.12 mmol/litre) and metabolic acidosis (arterial pH 6.96 +/- 0.11) developed after approximately 14 days of infection. Hypoglycaemia was associated with appropriate suppression of plasma insulin concentrations. In a second series of experiments the metabolic effects of treatment with glucose (500 mg/kg/hr), quinine (5 mg/kg bolus followed by 10 mg/kg over 1 hr) and a potent activator of pyruvate dehydrogenase, dichloroacetate (300 mg/kg) were studied over a 1-hr period. In control animals quinine had no measurable effects, but dichloroacetate significantly reduced arterial blood lactate (74%) and pyruvate (80%). In infected animals, glucose infusion attenuated the rise in lactate (38% compared with 82%; P less than 0.01) but quinine had no additional metabolic effects. Dichloroacetate further attenuated the rise in lactate (14%; P less than 0.01). PMID- 1901270 TI - Schistosoma mansoni: higher free proline levels in the livers of infected mice. AB - The concentration of L-hydroxyproline in the liver of ICR female mice increased rapidly during the 8th to 11th weeks of Schistosoma mansoni infection. Free L proline concentration began to increase about the 7th week and reached its maximum at the 8th to 9th weeks of the infection, when the granulomatous response to the schistosome eggs in the liver was most prominent, as indicated by the increase in liver wet weight and its deoxyribonucleic acid concentration. A significant increment in the total activity of ornithine-delta-transaminase (EC 2.6.1.13) and the decrease in the specific activity of proline oxidase (EC 1.4.3.2) became detectable in the liver homogenate of infected mice on the 8th week. However, changes in these enzymatic activities were not parallel to that of the hepatic free L-proline content. Intraperitoneal administration of S. mansoni egg granulomas or 15,000g x 30 min supernatant fluid of their extracts into uninfected, normal mice significantly increased the hepatic free L-proline content without any appreciable effect on the enzymatic activities of proline oxidase and ornithine-delta-transaminase. These findings suggest that S. mansoni egg granulomas contain a factor(s) which may be responsible for the elevation of free L-proline content in the fibrotic liver caused by experimental schistosomiasis mansoni. PMID- 1901271 TI - Trypanosoma brucei: cytotoxicity of host high-density lipoprotein is not mediated by apolipoprotein A-I. PMID- 1901272 TI - Chronic myeloid leukaemia lymphoid blast crisis. Relevance of molecular analysis at the bcr and immunoglobulin heavy chain gene level in monitoring response to therapy and residual disease. AB - Southern blot analyses were performed in sequential DNA samples from 4 patients with Ph' + chronic myeloid leukaemia (CML) who underwent lymphoid or mixed blast crisis (BC). Genomic rearrangements at the breakpoint cluster region (bcr) and immunoglobulin heavy chain (IgH) gene level provided, in these cases, a sensitive and specific evaluation of response to therapy both in terms of blasts and Ph' + cell suppression. Recurrent BC was molecularly characterized in the 4 patients, showing each time identical individual specific DNA rearrangement patterns. Residual blasts were detected in 2 cases during intervening chronic phases by IgH rearrangements. Such findings highlight the specificity of these molecular markers, clearly indicating the failure of ablative therapy in eradicating the neoplastic clone. Finally, molecular and phenotypic identity in individual recurrent BC also suggested, in our cases, a lack of clonal evolution during disease progression. PMID- 1901273 TI - Bernard-Soulier syndrome in two Swedish families: effect of DDAVP on bleeding time. AB - We present 2 patients with Bernard-Soulier syndrome from two different families. The parents of one of the patients were found to have had common ancestors in the 17th century. The platelet membrane content of glycoprotein (GP)Ib was measured in the patients and their first-degree relatives with an ELISA technique based on monoclonal antibodies. Both patients had very low levels of GPIb. In one of the families the heterozygotes had reduced expression of GPIb but in the other the obligate heterozygotes had normal values, suggesting that the molecular pathology differs between the two families. In both patients, bleeding time was shortened by infusion of DDAVP (1-deamino-8-D-arginine vasopressin), although it was not completely normalised. DDAVP may be of some therapeutic value in cases of Bernard Soulier syndrome. PMID- 1901274 TI - The effects of glucocorticoid hormone on the expression of c-jun. AB - The effects of glucocorticoid hormone on the expression of c-jun in the fibroblasts were studied. The expression of c-jun was repressed by dexamethasone in the NIH3T3 cells, but not in the transformed B104-1 or EJ-Ras cells. The repression was not relieved by the addition of cycloheximide. PMID- 1901275 TI - Interferon-gamma binds to heparan sulfate by a cluster of amino acids located in the C-terminal part of the molecule. AB - Using three different approaches (domain mapping with monoclonal antibodies, limited enzymatic digestion and competition with synthetic peptides), we demonstrated that a cluster of basic amino acids on interferon-gamma is involved in its binding to heparan sulfate. This cluster (Lys125-Arg131) is localized in the C-terminal part of IFN-gamma. Once bound to heparin sulfate, IFN-gamma is protected against protease attack. PMID- 1901276 TI - Purification of a lipoxygenase from ungerminated barley. Characterization and product formation. AB - Lipoxygenase was purified from ungerminated barley (variety 'Triumph'), yielding an active enzyme with a pI of 5.2 and a molecular mass of approximately 90 kDa. In addition to the 90 kDa band SDS-PAGE showed the presence of two further proteins of 63 kDa. Western blot analysis showed cross-reactivity of each of these proteins with polyclonal antisera against lipoxygenases from pea as well as from soybean, suggesting a close immunological relationship. The 63 kDa proteins appear to be inactive degradation products of the active 90-kDa enzyme. This barley lipoxygenase converts linoleic acid mainly into (9S)-(10E,12Z)-9 hydroperoxy-10,12-octadecadienoic acid, and arachidonic acid into (5S) (6E,8Z,11Z,14Z)-5-hydroperoxy-6,8,11,14-eic osatetraenoic acid. PMID- 1901277 TI - Intramitochondrial formation of oxidized glutathione during the oxidation of benzylamine by monoamine oxidase. AB - Oxidation of benzylamine by MAO results in an accumulation of GSSG in mouse liver mitochondria. Formation of GSSG is prevented by deprenyl, an inhibitor of MAO-B, but not by catalase. GSSG accumulation also occurs with dopamine as substrate. Oxidation of monoamines by mitochondrial MAO represents a potential oxidant stress for mitochondria. PMID- 1901278 TI - Abnormal pattern of luteinizing hormone pulsatility in women with epilepsy. AB - Dysfunction of the hypothalamic-pituitary-ovarian axis in epileptic females has been suggested in the latest years. To further elucidate this issue, we assessed reproductive endocrine function in 10 normally cycling, drug-free epileptic women and in 5 normal controls, evaluating the basal hormonal profile and luteinizing hormone (LH) pulsatility in the midfollicular phase. Luteinizing hormone pulse frequency was significantly higher in epileptic women with a consequent reduction of the LH interpulse interval. We suggest that epilepsy may interfere with the functional activity of the gonadotropin-releasing hormone pulse generator. The pathogenetic mechanisms for this phenomenon may be the spreading of paroxysmal activity within the hypothalamic areas or, alternatively, a neurotransmitter dysfunction giving rise both to the seizure disorder and to the abnormal LH pulsatile pattern. PMID- 1901279 TI - Secretory changes in preovulatory endometrium during controlled ovarian hyperstimulation with buserelin acetate and human gonadotropins. AB - Twenty-one patients with unexplained infertility underwent controlled ovarian hyperstimulation with buserelin acetate and human menopausal and chorionic gonadotropins, and follicular growth was monitored by ultrasonography and daily 17 beta-estradiol (E2) assays. Endometrial biopsy was performed when E2 levels were greater than or equal to 250 pg/mL per follicle and the follicular diameter was greater than or equal to 17 mm. As controls, we studied 20 preovulatory endometrial biopsies from patients with a male infertility factor. The biopsy material was examined at light, scanning, and transmission electron microscopes, and a morphometric analysis was performed. Preovulatory endometrial mucosa during controlled ovarian hyperstimulation showed accentuated proliferative aspects in both the glandular and stromal components and more frequent early secretory phenomena compared with the controls. The preovulatory progesterone (P) levels observed in our study seem to exclude the possibility that such early secretory aspects of the hyperstimulated endometrium are because of higher P concentrations in patients compared with controls. PMID- 1901280 TI - Improvement of spontaneous pregnancy rate after stopping gonadotropin therapy for anovulatory infertility. AB - In a prospective study, 140 patients with infertility because of ovulatory factors (group A) were followed up for 6 months after failure to achieve pregnancy using human menopausal gonadotropin (hMG) therapy. They included cases of oligomenorrhea, polycystic ovarian disease (PCOD), and hypogonadotropic amenorrhea. They were treated with hMG alone or in combination with clomiphene citrate or gonadotropin-releasing hormone agonist analog. The control group (B) included 83 infertile patients because of similar ovulatory factors. They were followed up for 6 months not preceded by ovulation induction. The overall pregnancy rate (PR) in group A (20.7%) was significantly higher than group B (7.2%). The PR was significantly higher in oligomenorrhea and PCOD patients when compared with the control group. There was no significant difference in the hypogonadotropic group. PMID- 1901281 TI - Characteristics of ovarian follicular development in Norplant users. AB - Daily transvaginal ultrasound (US) scanning of the ovaries to assess follicular development and daily blood sampling were performed on 19 Norplant (Leiras, Turku, Finland) subdermal contraceptive implant users who had regular menstrual cycles and on 10 normally cycling women. Three groups were identified in the implant users based on US finding. Six (31.6%) of the implant users had US findings that were consistent with a normal ovulatory pattern. However, their mean peak luteinizing hormone levels and peak midluteal phase progesterone (P) levels were significantly lower than control values. Eleven (57.9%) users had persistent follicles, and 2 users (10.5%) had no follicular development. These data suggest that after 2 to 4 years of use, about one third of Norplant users with regular bleeding patterns may ovulate but most have deficient luteal P levels. In this small study, the presence of persistent follicular enlargement in implant users was common. PMID- 1901282 TI - Basal follicle-stimulating hormone level is a better predictor of in vitro fertilization performance than age. AB - A study of 1,478 consecutive in vitro fertilization (IVF) cycles was made to determine if basal follicle-stimulating hormone (FSH) levels and age were independent predictors of IVF performance. Regression analyses indicated independent contributions of both basal FSH and age in predicting cancellation rate, peak estradiol, number of oocytes retrieved, fertilized, and transferred, and total and ongoing pregnancy rates. Miscarriage rate was unrelated to both age and basal FSH. Follicle-stimulating hormone level was a better predictor than age for all outcome variables examined and remained a significant predictor after accounting for age, etiology of infertility, and semen quality. The combined use of age and basal FSH in counseling patients improves the accuracy of prognosis, and may provide an index of functional ovarian reserve ("ovarian age"). PMID- 1901283 TI - Stimulation cycles suppressed with gonadotropin-releasing hormone analog yield accelerated embryos. AB - A retrospective study was performed to assess embryonic development and morphology in 71 patients whose follicular stimulation was regulated after down regulation with a gonadotropin-releasing hormone analog, leuprolide acetate. The embryos were compared with those from 66 patients who did not receive agonists and who were treated during the same period. A separate group of thawed embryos cryopreserved after down regulation in 21 patients was compared with embryos frozen after conventional stimulation during the same period from 21 other patients. Eleven morphological criteria were assessed in the fresh embryos, and analyses did not reveal any differences between the groups studied. However, the rate of development of embryos obtained during down-regulated cycles was significantly higher than that of embryos developing in conventional stimulation cycles. Although no significant morphological differences could be shown between the groups of cryopreserved embryos, there was a decreased incidence of implantation of embryos from patients who were exposed to analogs. It is suggested that embryos from down-regulated cycles should be cryopreserved earlier to correct for their accelerated development. PMID- 1901284 TI - Variations of luteinizing hormone serum concentrations after exogenous human chorionic gonadotropin administration during ovarian hyperstimulation. AB - Changes in luteinizing hormone (LH), estradiol, and progesterone (P) serum levels before and after preovulatory administration of human chorionic gonadotropin (hCG) were assayed in 30 patients stimulated with clomiphene citrate (CC) and human menopausal gonadotropin (hMG) and compared with LH variations in 43 patients submitted to pharmacological hypophysectomy with a gonadotropin releasing hormone agonist (GnRH-a) and stimulation with hMG. In CC + hMG-treated patients, an endogenous LH surge occurred systematically 4.25 +/- 2.75 hours after hCG injection. Multiparametric analysis indicated an inverse correlation between the delay in the initial rise of the LH surge and the increase in P levels during the 6 hours after hCG administration. Gonadotropin-releasing hormone agonist + hMG treatment did not lead to an LH surge after hCG but to a significant fall in LH levels. Thus, exogenous hCG, administered before ovulation, induces an endogenous LH surge if pituitary function is not blocked by a GnRH-a, probably through an increase in P secretion. PMID- 1901285 TI - Metamorphosis of the corpus allatum and degeneration of the prothoracic glands during the larval-pupal-adult transformation of Drosophila melanogaster: a cytophysiological analysis of the ring gland. AB - The degeneration of the prothoracic glands of Drosophila melanogaster during pupal-adult metamorphosis was analyzed by light microscopy, scanning, and transmission electron microscopy. The ultrastructural observations were correlated with the ability of the ring gland to synthesize ecdysteroids in vitro. The ring gland is prominent during larval life and is identifiable until just before adult eclosion but undergoes dramatic changes in location, shape, size, ultrastructure, and function during pupal-adult development. Prothoracic gland degeneration is characterized by: a gradual decrease in its ability to synthesize ecdysteroids; a decreasing quantity of smooth endoplasmic reticulum (SER) and mitochondria; the absence of intercellular channels; cytoplasmic fragmentation; and the separation of the prothoracic gland from the corpus allatum and corpus cardiacum. An ultrastructural analysis of the corpus allatum during larval-pupal-adult metamorphosis and adult life was also correlated with function, i.e., juvenile hormone biosynthesis, using a radiochemical assay of ring glands and adult corpora allata in vitro. A relatively high concentration of SER, mitochondria, and mitochondrion-scalariform junction complexes are typical features of an active corpus allatum cell. The migration of the corpus allatum from the ring gland to its position as a separate gland in the adult fly was studied in detail. The capacity of the corpus allatum to synthesize juvenile hormone is at its peak in the ring gland of the early wandering third instar larva, whereas the corpus allatum of 2-day-old female adults displayed the greatest synthetic activity during adult life. The physiological significance of the alterations in gland activity is discussed. PMID- 1901286 TI - Gamma-interferon promotes differentiation of cultured cortical and hippocampal neurons. AB - Clinical and experimental evidence suggests that the development of the brain may be modulated by soluble growth factors traditionally associated with cells of the immune system. As part of an investigation into agents modulating early neural differentiation, we examined the effects of the lymphokine gamma-interferon (IFN gamma) on the development of cultured cortical and hippocampal neurons from embryonic rats and mice. We report here that recombinant IFN-gamma, at concentrations of 0.2-10 U/ml (50-2500 pg/ml, 3-150 pM), affects the differentiation of embryonic central neurons. IFN-gamma increased the number of cells expressing neurofilament (NF) protein, the growth of primary and secondary neurites on NF-expressing somas, and the extent of cell aggregation observed in culture. IFN-gamma-induced increases in the numbers of NF-positive cells were seen in the virtual absence of differentiated astrocytes, and in mixed neuron glia cultures. Our results thus indicate that at physiologically relevant concentrations IFN-gamma acts, either directly on neurons and their precursor cells and/or indirectly via nonneuronal cell stimulation, to promote the differentiation of immature neurons. PMID- 1901287 TI - Early ventral expression of the Drosophila neurogenic locus mastermind. AB - The neurogenic locus mastermind (mam) of Drosophila is required for the segregation of epidermal from neural cell lineages. Previous studies have shown that during neurogenesis mam appears to be expressed throughout the ectoderm, mesoderm, and neuroblast layer of the germ band. Here it is demonstrated that during early embryogenesis mam is expressed ubiquitously; however, the predominant domains of accumulation of mam RNA and protein during gastrulation are along the ventral longitudinal surface, including cells of the mesoderm, endoderm, mesectoderm, and neuroectoderm. The regions of elevated mam accumulation coincide with the realm of action of dorsoventral patterning genes. PMID- 1901289 TI - [Intestinal motility in patients with small bowel diverticulosis]. AB - It has been demonstrated that motility disorders may be responsible for esophageal and colon diverticulosis. Recently anatomic alterations of both small bowel muscular layers and myenteric plexus have been described in patients with small bowel diverticulosis. Such pathological features could be responsible for motility disorders and small bowel diverticulosis formation. The aim of this work was to study the small bowel motility in patients with small bowel diverticulosis. Ten patients (mean age: 69.2 +/- 6 years mean +/- SEM) with more than 3 diverticula in the jejunum or the ileum (excepting duodenal diverticulum) were studied. After an overnight fast, a 4 lumen probe (side holes 10 cm apart) was used to record duodeno-jejunal motility for 4 hours. Esophageal manometry was also performed in 8 patients. The mean number of phase 3 of the migrating motor complex (mean +/- SEM) during 4 hours was significantly lower in patients with small bowel diverticulosis (0.15 +/- 0.05/hours; mean +/- SEM) than in 10 normal volunteers (0.52 +/- 0.07/hours; mean +/- SEM) (P less than 0.01); 5 patients had zero phase 3 during the 4 hours of recording; one patient displayed intestinal hypomotility associated with aberrant phase 3 like activity; 4 patients showed simultaneous minute-rhythm during more than 80 percent of the phase 2 of the migrating motor complex. Esophageal manometry was also disturbed in 6 patients (low amplitude contractions less than 30 cm H2O in the distal esophagus). Bacterial overgrowth was investigated in 8 patients by means of a glucose breath test and was found in 6 cases. In conclusion, duodeno jejunal motility is altered in patients with small bowel diverticulosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1901288 TI - Role of phospholipase in generating lipid second messengers in signal transduction. AB - Many lipids or lipid-derived products generated by phospholipases acting on phospholipids in membranes are implicated as mediators and second messengers in signal transduction. Our current understanding of the primary sequence relationships within the class of extracellular phospholipase A2's and among the numerous forms of the mammalian phosphatidylinositol-specific phospholipase C's is reviewed. New results suggesting roles for these phospholipases as well as other phospholipases such as phospholipase C and D acting on phosphatidlycholine in generating arachidonic acid for eicosanoid biosynthesis, inositol phosphates for Ca2+ mobilization, and diglyceride for protein kinase C activation through receptor-mediated processes, are discussed. In addition, the possible role of phospholipases acting on sphingolipids such as sphinglomyelinase in generating lipid mediators is considered. PMID- 1901290 TI - Comparison of the long-term effects of estrogen and clomiphene citrate on pituitary and uterine function in ovariectomized rats. AB - The effects of estradiol-17 beta (E2) and clomiphene citrate (CC) on pituitary uterine function in ovariectomized (OVX) rats were compared in two experiments. In experiment 1, CC completely blocked E2 stimulation of uterine weight when administered concurrently for 10 and 30 days. In experiment 2, content of total (occupied and unoccupied) uterine nuclear estrogen receptors was increased by E2, but not by CC, compared to OVX controls. Only a fraction of the nuclear receptors was occupied in E2-treated rats, whereas all of these receptor sites were occupied in CC-treated rats. In addition, uterine cytoplasmic estrogen receptors were increased by E2 and diminished by CC treatment. Both E2 and CC were effective in preventing the postovariectomy rise in serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH), although LH was always inhibited to a greater extent than FSH. After 30 days of treatment, pituitary gonadotropins were also substantially reduced by E2 and CC, suggesting that long-term treatment decreased both pituitary synthesis and release. An increase in pituitary weight observed in E2-treated rats only was due largely to the stimulation of lactotropes, as serum prolactin was increased. In summary, although CC and E2 similarly depressed pituitary gonadotropin secretion, they exhibited marked differences in the stimulation and occupancy of uterine estrogen receptors and the stimulation of pituitary prolactin secretion. PMID- 1901291 TI - Recurrence of hepatitis C virus infection after orthotopic liver transplantation. AB - Identification of the hepatitis C virus--the main cause of posttransfusion and sporadic non-A, non-B hepatitis--and the development of a diagnostic serological test have allowed us to study possible recurrence of this type of hepatitis after liver transplantation. Six of 34 consecutive transplant recipients were found to have had antibodies to hepatitis C before transplantation. All six patients had possible exposure to hepatitis C through blood transfusion or intravenous drug use. Five of the six patients were positive for antibodies to hepatitis C after 1 yr of follow-up. Two of these patients had clinical and histological evidence of acute viral hepatitis in their allografts. In one patient this led to hepatic injury and dysfunction of two successive grafts. In contrast, none of the twenty eight patients who were seronegative for hepatitis C virus antibodies before transplantation has converted to seropositivity after transplantation despite perioperative blood transfusions. These results suggest that hepatitis C diagnosed serologically recurs in a minority of transplant recipients and that de novo seroconversion must be uncommon. PMID- 1901293 TI - Potential importance of the sexual transmission of non-A, non-B hepatitis. PMID- 1901292 TI - Is glucuronidation truly preserved in patients with liver disease? PMID- 1901295 TI - HCFA pilot project may bolster hospital-physician collaboration. AB - A new HCFA pilot project will probe the feasibility and cost-effectiveness of paying hospitals and physicians one negotiated package fee for coronary artery bypass surgery. If successful, the pilot may be expanded to other procedures, ultimately forcing hospitals and physicians to seek new avenues of negotiation to determine how to split the lump-sum payments. Find out how the hospital executives in this project negotiated with their physicians. PMID- 1901294 TI - The pattern of amyloidosis in a Malaysian patient population. AB - Congo red screening of 27,052 routine biopsy specimens from 22,827 patients over a 5 1/2-year period in the Department of Pathology, University of Malaya detected 186 cases of amyloidosis. The categories of amyloidosis encountered and their prevalences in relation to each other were: systemic AL (5.9%); systemic AA (3.2%); isolated atrial (14%); primary localized cutaneous (7.5%); other primary localized deposits (3.2%); localized intratumour (58%); and dystrophic (8.6%). A third of patients with systemic AL amyloidosis had coexistent immunocyte abnormality. The commonest underlying pathology for systemic AA amyloidosis was leprosy. Notable among the types of localized amyloidosis revealed by this study were isolated atrial amyloidosis, which appeared to complicate chronic rheumatic heart disease, and intratumour amyloidosis complicating nasopharyngeal carcinoma. Other tumours in which amyloid deposits were observed included basal cell carcinoma, islet cell tumour and medullary carcinoma of the thyroid. Dystrophic amyloidosis was observed in fibrotic tissues, such as damaged cardiac valves and osteoarthritic joints. Heredofamilial amyloidosis, senile systemic amyloidosis and degenerative cerebral amyloidosis were notably absent from this study. PMID- 1901296 TI - The PVG-RT1r1 rat carries the HLA-DP-like (RT1.H) alpha and beta genes of the DA strain. PMID- 1901297 TI - Production of monoclonal antibodies reactive with polymorphic and monomorphic determinants of SLA class I gene products. PMID- 1901298 TI - Estradiol modulation of plasminogen activator production in organ cultures of human breast carcinomas: correlation with clinical outcome of anti-estrogen therapy. AB - We have studied the estradiol sensitivity of primary human breast carcinomas in organ culture in a prospective pilot series of 109 tumors. The effect on plasminogen activator (PA) production was used as the end-point of estrogen action. We found that: (i) All tumors secreted detectable levels of urokinase type PA (uPA); the level of basal uPA production was markedly heterogeneous but showed a weak association with the level of estrogen receptor positivity (p = 0.049). (ii) Only 23.5% of the tumors secreted tissue-type PA (tPA) in addition to uPA; a higher proportion of these tumors had histological characteristics indicative of good prognosis (18% vs. 3% of tumors secreting only uPA). (iii) Estradiol modulated uPA production and this effect was receptor-mediated. (iv) Responsiveness to estradiol was limited to a subset (25 of 60 or 41.7%) of estrogen and progesterone-receptor-positive tumors. (v) Of 20 evaluable patients with lymph-node and receptor-positive breast cancer who received adjuvant anti estrogen therapy, 11 were identified as estradiol-sensitive by the in vitro PA assay; of these, 10 had no evidence of disease after a median follow-up period of 3+ years. In contrast, of 9 patients with tumors identified as estradiol insensitive, 4 developed metastases within 3+ years of follow-up. (vi) Consistent with the previously reported inhibitory effect of corticosteroids on uPA production in organ cultures of human tumors, the basal culture level of uPA produced by tumors from patients receiving corticosteroids at the time of surgery was significantly lower than the level of uPA in the remaining tumors (p = 0.029). Also, tumors from patients receiving thyroid hormone, known to stimulate uPA in vitro, showed a slight trend toward increased production of uPA. These results show that hormone effects on tumor PA production are qualitatively similar in organ culture and in the host. This and the emerging individual correlation between sensitivity to estradiol in vitro, as determined by PA, and the clinical effectiveness of anti-estrogen therapy, underscore the potential usefulness of the organ culture approach. PMID- 1901299 TI - Thyrotropin releasing hormone (TRH) immunoreactivity and thyroid function in obesity. AB - Circulating TRH-immunoreactive levels, the thyrotropin response to a TRH intravenous stimulation (200 micrograms) and thyroid hormone concentrations have been determined in 43 overweight subjects (body mass index 45 +/- 12 kg/m2, mean +/- s.d.) and 46 (body mass index 22 +/- 2 kg/m2) normal weight controls. The TRH levels measured by a recently developed, highly specific radioimmunoassay were similar among both groups (44 +/- 16 vs 40 +/- 12 fmol/ml, n.s.). The pattern of response of TSH to TRH was normal in the obese and no significant difference was observed between the peak TSH values of the obese and the normal group (8.3 +/- 2.8 vs 8.7 +/- 2.2 microU/ml, n.s.). No correlations were found between the degree of obesity and the concentrations of TRH, TSH and peripheral thyroid hormone levels. Three obese patients showed a delta-TSH of 18, 19 and 21 microU/ml at normal thyroid hormone concentrations as sign of latent hypothyroidism. These data indicate that in obesity: (a) the TSH response to i.v. TRH is not impaired, (b) circulating TRH-IR levels are not significantly changed and (c) the incidence of overt hypothyroidism is not increased. PMID- 1901300 TI - Aldose reductase inhibitors and cataract. AB - Blindness in diabetics is largely due to retinopathy and/or cataract. Hyperglycaemia and the duration of diabetes are major risk factors for the development of cataract and retinopathy. This review details some of the reactions of glucose that are relevant to the development of complications, and follows the elucidation of monosaccharide autoxidation and its relevance to the aldose reductase reaction and its determination. Inhibitors of this 'aldose reductase' reaction are shown to have a number of effects which may be of importance to their action in vivo. The pharmacological implications of chemotherapy for diabetics with complications are briefly discussed. PMID- 1901301 TI - Mechanistic aspects of 1-methyl-4-phenyl pyridinium iodide toxicity in Escherichia coli: the role of oxygen and hydrogen peroxide. AB - 1-Methyl-4-phenyl pyridinium iodide (MPP+) and paraquat (PQ+2) are two structurally analogous and highly toxic pyridinium compounds. The mechanism of PQ+2 toxicity is best understood in the bacterial model system. While numerous studies in a variety of systems have indicated the causative role of free radicals and other oxygen-derived active species in PQ+2 toxicity, this question is yet unresolved in the case of MPP+. In this study we have used the Escherichia coli model and demonstrated that MPP+ is toxic to bacterial cells in dose- and time-dependent modes. Additionally, it is shown that only in the presence of molecular oxygen did bacterial inactivation occur. This requirement for oxygen can be circumvented by adventitious H2O2. The protective effects of the chemical scavenger--mannitol--and of histidine are presented. These results are in complete accord with a free radical mechanism for MPP+ toxicity. PMID- 1901302 TI - Relationship between genotypes of longevity genes and developmental speed in Drosophila melanogaster. AB - Hatching time (the period between egg-laying and hatching) and emerging time were surveyed and their relationship with the adult life span was investigated. A relationship between emerging time and adult life span was clearly evident: early emergers were often long-lived. This relation is considered to have a genetic basis because all the larvae in a group were bred in the same culture bottle. Thus, the longevity genes involved also appear to have control over the rate of development. No significant relation was observed between hatching time and adult life span or between hatching time and emerging time. These results suggest that the function of the longevity genes begins at the larval or pupal stage before emergence, and that adult life spans differentiate at this time. PMID- 1901303 TI - On the developmental theory of ageing. I. starvation resistance and longevity in Drosophila melanogaster in relation to pre-adult breeding conditions. AB - The developmental theory of ageing predicts a positive correlation between developmental time and adult longevity. Experiments that vary larval density and food level have been carried out to test this prediction. The results show differences in viability, developmental time, starvation resistance and adult longevity. It is concluded that pre-adult developmental time is not a causal factor for the determination of adult longevity in Drosophila melanogaster. The observed variation in adult longevity is discussed in relation to viability selection and changed adult physiology. PMID- 1901304 TI - Low activity sn-glycerol-3-phosphate dehydrogenase variants in natural populations of Drosophila melanogaster. AB - Eleven Australian natural populations of Drosophila melanogaster were screened by electrophoresis for evidence of null and/or low activity variants at the Gdph locus. Of 5018 alleles investigated, 57 had markedly lower GDPH activity, as judged by their heterozygous phenotypes, than control alleles. GPDH assays of 13 of these variant alleles showed that whilst they were heterogeneous in their properties and included electrophoretic variants and two categories of low activity variant, there were no true null alleles. The most common low-activity variants exhibited dominance for GPDH activity in heterozygotes with normal alleles, and were shown to share this property with an allele previously isolated from a London (UK) population (Langley et al., 1981). PMID- 1901305 TI - Comparison of three methods of feeding colostrum to dairy calves. AB - Absorption of colostral immunoglobulins by Holstein calves was studied in 3 herds in which 3 methods of colostrum feeding were used. Failure of passive transfer, as determined by calf serum immunoglobulin G1 (IgG1) concentration less than 10 mg/ml at 48 hours of age, was diagnosed in 61.4% of calves from a dairy in which calves were nursed by their dams, 19.3% of calves from a dairy using nipple bottle feeding, and 10.8% of calves from a dairy using tube feeding. The management factor determined to have the greatest influence on the probability of failure of passive transfer in the herds using artificial methods of colostrum feeding (bottle feeding or tube feeding) was the volume of colostrum fed as it affected the amount of IgG1 received by the calf. In dairies that used artificial feeding methods, failure of passive transfer was infrequent in calves fed greater than or equal to 100 g IgG1 in the first colostrum feeding. In the dairy that allowed calves to suckle, prevalence of failure of passive transfer was greater than 50% even among calves nursed by cows with above-average colostral IgG1 concentration. Analysis of the effect of other management factors on calf immunoglobulin absorption revealed small negative effects associated with the use of previously frozen colostrum and the use of colostrum from cows with long nonlactating intervals. PMID- 1901307 TI - Ileal diverticulum as a cause of chronic colic in a horse. AB - A 4-year-old Thoroughbred gelding with a history of chronic colic was referred for evaluation of signs of abdominal pain. Exploratory laparotomy revealed a diverticulum of the distal portion of the ileum located between the layers of the mesentery. The diverticulum was similar in location and appearance to acquired ileal diverticula described in human beings. Complete bypass of the diverticulum by ileocecostomy resulted in apparent resolution of the chronic colic in this horse. PMID- 1901308 TI - Specific regulatory actions of dihydrotestosterone and estradiol on the dynamics of FSH secretion and clearance in humans. AB - The authors investigated immunoactive and bioactive follicle-stimulating hormone (FSH) secretion and clearance in six healthy young men during steady-state infusions of vehicle (basal, B, 28 hours), dihydrotestosterone (DHT, 4.5 days), or estradiol (4.5 days) accompanied by blood sampling at 10-minute intervals for 28 hours. Serum FSH concentrations were assayed by a two-site immunoradiometric assay (IRMA) and two separate in vitro bioassays (rat granulosa and Sertoli cell systems). FSH measurements included: 24-hour mean serum concentrations (IRMA and bioassay), multiple-parameter deconvolution of 24-hour pulsatile FSH time series and FSH release in response to exogenous gonadotropin-releasing hormone (GnRH) boluses (IRMA) to assess secretion and clearance, and circadian serum FSH concentration rhythms by cosinor analysis (IRMA). We found: 1) a significant decrease in 24-hour mean IRMA FSH concentrations during DHT infusion while both in vitro estimates of FSH bioactivity were unchanged; 2) significant decreases in the mass of IRMA FSH secreted per 24 hours during DHT infusion; 3) significant decreases in the IRMA FSH half-life during estradiol infusion without any change in FSH interpulse interval; 4) no steroidal effects on FSH secretory responses to exogenous GnRH; and 5) abolition of basal circadian FSH rhythms during sex steroid infusions. Based on these findings, we conclude that steady-state sex steroid hormone infusions selectively alter IRMA FSH secretion and clearance without affecting IRMA FSH pulse frequency or mean concentrations of bioactive FSH. PMID- 1901306 TI - Acute sarcocystosis-like disease in a dog. AB - Two of 8 littermate Rottweiler dogs developed persistent diarrhea at 6.5 weeks of age. Dog 1 was euthanatized at 14 weeks of age and had hepatitis characterized by necrosis and mixed leukocyte infiltrations in association with a previously unrecognized Sarcocystis-like protozoon. The organism was free in the hepatocyte cytoplasm without a parasitophorous vacuole, had divided by schizogony, and stained with anti-Sarcocystis serum, but did not stain with anti-Toxoplasma gondii or anti-Neospora caninum serum in an immunohistochemical test. Dog 2 was euthanatized at 10 weeks of age. This dog had large necrotic, hemorrhagic mesenteric lymph nodes. Numerous T gondii tachyzoites were observed in association with these lesions. The organism divided by endodyogeny and stained specifically with anti-T gondii serum. PMID- 1901309 TI - Response of circulating gonadotropin levels to GnRH agonist treatment in prostatic cancer. AB - Luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone (T) responses to 6-month treatments with a gonadotropin-releasing hormone (GnRH) agonist (buserelin) and subsequent orchiectomy were studied in patients with advanced prostate cancer. For treatments, either an intranasal (600 micrograms, 3/day, n = 8) or subcutaneous depot preparation (6.6 mg every other month, n = 5) were used. A third group of patients received intranasal buserelin (400 micrograms, 3/day, n = 12) for 35 months. LH and FSH were measured using radioimmunoassay (RIA) and a sensitive (0.04 IU/L) immunofluorometric assay (IFMA). In addition, selected samples were analyzed for bioactive (bio) LH. The RIA-LH levels decreased 70% with intranasal treatment. In contrast, when monitored by IFMA, the reduction was greater than 90%: 0.2 to 0.3 IU/L with intranasal and 0.044 to 0.052 IU/L with depot treatment (P less than 0.01). Gonadotropin suppression was stable up to 35 months. Bio-LH and IFMA-LH levels decreased in parallel during treatment, with no apparent changes in the bio/immuno ratio. FSH levels were suppressed temporarily during the treatments. After castration and cessation of buserelin treatment, serum LH and FSH increased rapidly in the intranasal treatment group but only marginally during 3 months in the depot group. Serum T reached the castrate range when IFMA-LH decreased below 0.5 IU/L. A further decrease in LH (less than 0.1 IU/L) still suppressed the intratesticular T concentration measured after orchiectomy. In conclusion, IFMA offers an improved method to monitor the antigonadotropic effect of GnRH agonist treatment. The results emphasize the necessity of profound LH suppression to achieve maximal inhibition of testicular androgen production. PMID- 1901310 TI - WF-2421, a new aldose reductase inhibitor produced from a fungus, Humicola grisea. AB - WF-2421 is a novel aldose reductase inhibitor produced by Humicola grisea. WF 2421 was purified from the culture filtrate by successive ion exchange chromatography and the chemical structure was assigned to be alpha-formamido-5' (2-formamido-1-hydroxyethyl)- beta,2',6-trihydroxy-3-biphenylpropanoic acid (1) on the basis of spectroscopic evidence. The IC50 value of WF-2421 was 3 x 10(-8) M against partially purified aldose reductase of rabbit lens. PMID- 1901311 TI - Synthesis and cytostatic properties of daunorubicin derivatives, containing N phenylthiourea or N-ethylthiourea moieties in the 3'-position. AB - A series of phenylthiourea and ethylthiourea derivatives of daunorubicin and its congeners was prepared by reaction of the 3'-amino group of the antibiotic with phenylisothiocyanate or ethylisothiocyanate. S-Methylation yielded S methylisothiouromium salts which when reacted with amines resulted in an intramolecular cyclization with the participation of the neighboring 4'-OH group. The structures and predominant conformations of the thiourea derivatives and daunorubicino(3'-N,4'-O-d)oxazolines were determined by 1H and 13C NMR. Cytostatic activities of the thiourea and oxazoline derivatives were compared with the cytostatic activities of N-methylurea and N-methyl-N-nitrosourea containing daunorubicin and its congeners. Carminomycin derivatives were endowed with the highest cytostatic activity. PMID- 1901312 TI - Synthesis and antibacterial activity of new C-10 quinolonyl-cephem esters. AB - A series of cephalosporins derived from cephalothin containing an ester-linked quinolonyl substituent at the C-10 position (C-10 quinolonyl-cephem esters) has been prepared and evaluated for in vitro antibacterial activity. The C-10 quinolonyl-cephem esters exhibited a broadened spectrum of activity when compared with cephalothin and the corresponding quinolones, including activity against beta-lactamase-producing bacteria. PMID- 1901313 TI - The use of beta-galactosidase gene fusions to screen for antibacterial antibiotics. AB - The desirable features for a screening assay to detect antibacterial antibiotics include 1) high specificity for the desired antibiotic type 2) high sensitivity 3) lack of interference by other compounds likely to be associated with the antibiotic of interest and 4) ease of operation to allow a large number of samples to be tested. These characteristics are largely found in screens employing strains carrying fusions between antibiotic induced promoters and the structural genes for Escherichia coli beta-galactosidase. Screens were designed based upon fusions with three antibiotic induced promoters: the tetracycline induced tetA/tetR promoter from transposon Tn10, the erythromycin induced promoter from the Staphylococcus aureus ermC erythromycin-resistance gene and the chloramphenicol induced promoter from the S. aureus cat86 chloramphenicol resistance gene. Because there have been no reports of vancomycin induced resistance determinants, a Tn903 random gene fusion pool was screened to isolate a vancomycin induced gene fusion. This gene fusion was induced fairly specifically by glycopeptide antibiotics and the fusion was used as the basis for a glycopeptide screen. PMID- 1901315 TI - A slow pulse after head and neck surgery. PMID- 1901314 TI - Effect of acute hypoxia on respiration and brain stem blood flow in the piglet. AB - Changes in local brain stem perfusion that alter extracellular fluid Pco2 and/or [H+] near central chemoreceptors may contribute to the decrease in respiration observed during hypoxia after peripheral chemoreceptor denervation and to the delayed decrease observed during hypoxia in the newborn. In this study, we measured the changes in respiration and brain stem blood flow (BBF) during 2-4 min of hypoxic hypoxia in both intact and denervated piglets and calculated the changes in brain stem Pco2 and [H+] that would be expected to occur as a result of the changes in BBF. All animals were anesthetized, spontaneously breathing, and between 2 and 7 days of age. Respiratory and other variables were measured before and during hypoxia in all animals, and BBF (microspheres) was measured in a subgroup of intact and denervated animals at 0, 30, and 260 s and at 0 and 80 s, respectively. During hypoxia, minute ventilation increased and then decreased (biphasic response) in the intact animals but decreased only in the denervated animals. BBF increased in a near linear fashion, and calculated brain stem extracellular fluid Pco2 and [H+] decreased over the first 80 s both before and after denervation. We speculate that a rapid increase in BBF during acute hypoxia decreases brain stem extracellular fluid Pco2 and [H+], which, in turn, negatively modulate the increase in respiratory drive produced by peripheral chemoreceptor input to the central respiratory generator. PMID- 1901316 TI - The importance of assessing iron status. PMID- 1901317 TI - Hemochromatosis and hepatitis C. PMID- 1901318 TI - Hemochromatosis, chondrocalcinosis, and hepatitis C. PMID- 1901320 TI - Significance of classifying antiarrhythmic actions since the cardiac arrhythmia suppression trial. AB - The Cardiac Antiarrhythmic Suppression Trial (CAST) showed flecainide and encainide induced excess mortality compared with placebo. Labeling drugs as Class 1C is based on clinical observations, comprising measurements of the electrocardiographic parameters QRS. H-V and J-T intervals and of effective refractory period (ERP) as follows: 1--(QRS) wide, 2--(HV) long, 3--(ERP) unchanged, 4--(JT) unchanged. In vitro electrophysiology helped to explain the clinical findings. Flecainide and encainide rendered Na channels as nonconducting, but F and E were only slowly released from the channels after repolarization. At any given drug concentration, a proportion of total channels were eliminated, and the steady-state proportion increased at rising heart rate. It is not proven that the properties that lead to classification of a drug as 1C were those that caused excess deaths in the CAST. The proarrhythmic tendency of 1C drugs can be reduced by beta-blockade, and the mechanisms of adrenergic arrhythmogenicity are discussed. Propafenone is both a 1C drug and a beta blocker, and its pharmacologic profile is reviewed to illustrate how it resembles and differs from flecainide and encainide. Some features of the CAST are assessed with particular reference to the extent to which conclusions drawn from the results may be justifiably extrapolated to other drugs classified as 1C. PMID- 1901319 TI - Estrogen monotherapy and combined estrogen-progestogen replacement therapy attenuate aortic accumulation of cholesterol in ovariectomized cholesterol-fed rabbits. AB - Cardiovascular disease is currently the leading cause of death among women in the United States. To investigate the effect of postmenopausal hormone therapy on atherogenesis, we studied 75 cholesterol-fed female rabbits for 19 wk. The rabbits were randomly assigned to five groups. Four groups underwent bilateral ovariectomy followed by treatment with either 17 beta-estradiol, 17 beta estradiol plus norethisterone acetate, 17 beta-estradiol plus levonorgestrel, or placebo. The fifth group had a sham operation and received placebo. The hormone groups had only one-third of the aortic accumulation of cholesterol found in the placebo groups, a difference that was highly statistically significant (P less than 0.0001). No significant differences in aortic accumulation of cholesterol were found in the hormone groups. This indicates that estrogen attenuates atherogenesis in cholesterol-fed ovariectomized rabbits and that two commonly prescribed progestogens do not counteract the effect. The beneficial effect of estradiol could only partly be explained by its lowering effects on serum total cholesterol or VLDL cholesterol, which implies that estradiol possesses additional beneficial effects, possibly a direct action on the arterial wall. PMID- 1901321 TI - An assessment of cerebral blood flow and metabolism after fleroxacin therapy. AB - Cerebral blood flow (CBF), glucose (FDG), and oxygen metabolism (OM) were evaluated by positron emission tomography (PET) in 18 healthy volunteers who were randomized to a 72-hour course of either 600 mg/d of fleroxacin or placebo. Such studies attempted to assess potentially serious, yet unexplained, central nervous system adverse effects of the fluorinated quinolone class. Baseline and postplacebo values for CBF (mL/min/100 g) and FDG (mg/min/100 g) were: 53 +/- 6 and 5.7 +/- 1.8; and 49.6 +/- 4.4, and 5.2 +/- 1.2, respectively. Identical values for fleroxacin were: 53.9 +/- 4.8 and 6.3 +/- 1.1; and 54.4 +/- 2.2 and 6.8 +/- 1.5, respectively. The differences between fleroxacin and placebo were not significant. There was also no effect seen in OM between placebo and the active drug. The authors conclude that short-term administration of fleroxacin does not alter CBF, FDG, or OM in healthy volunteers. PMID- 1901322 TI - Drug classification and actions. PMID- 1901323 TI - Protein and carbohydrate absorptive efficiency of chronically malnourished and well-nourished patients during enteral feeding initiation. AB - To investigate the efficiency of protein and carbohydrate absorption, we studied malnourished and well-nourished subjects during the first 72 hours of tube feeding. We furthermore investigated whether differences in absorptive efficiency existed between malnourished patients with and without nongastrointestinal malignancy. Twenty-one subjects starting tube feeding without edema or major organ failure and not on antibiotics (well-nourished controls = 7; malnourished = 7; malnourished with nongastrointestinal malignancy = 7) received 50 kcal/hr Osmolite continuously for 72 hours. Twelve of these subjects completed an additional 48 hours of study where they received 125 kcal/hr continuously. We performed hydrogen breath tests to assess carbohydrate absorption and determined stool nitrogen content to assess protein absorption. We also measured frequency of defecation, stool weight, and stool moisture content. The results of these tests failed to reveal statistically significant differences between the three groups in terms of protein and carbohydrate absorption, as well as failed to demonstrate the presence of diarrhea. We conclude that patients receiving an isoosmolar diet who are malnourished, or malnourished with nongastrointestinal malignancy, absorb carbohydrate and protein as well as well-nourished patients during enteral hyperalimentation. PMID- 1901324 TI - Zinc and copper status of severely burned children during TPN. AB - Alterations in zinc (Zn) and copper (Cu) homeostasis have been reported during the acute recovery period following thermal injury in both children and adults. Increased urinary losses of Zn and Cu and decreased plasma concentrations of Zn, Cu, and ceruloplasmin (CP), the major copper transport protein, occur despite adequate provision of these elements in enteral feedings. We now report data for moderately to severely burned children receiving total parenteral nutrition (TPN) supplemented to provide Zn and Cu. Hyperzincuria occurred consistently when 50 micrograms/kg Zn was delivered daily to older children. Similarly, when younger children received 100 micrograms/kg Zn daily, profound hyperzincuria ensued despite a reduction in total plasma Zn. Hypozincemia was accompanied by low levels of Zn in the plasma subfraction normally associated with albumin-bound Zn. The delivery of Cu via TPN was 4-12 micrograms/kg daily, and urinary Cu losses were not elevated. Plasma total Cu and plasma CP were invariably reduced. These findings are discussed in relation to guidelines published for pediatric trace element supplementation during TPN. PMID- 1901325 TI - Lactose and cataract in humans: a review. AB - In this review, the relationship between lactose and human cataract is examined from the presently available biochemical, metabolic, and epidemiological data. The exceptional cases of homozygous enzyme deficiency being excluded, fragmentary data give reason to believe that a risk of cataract secondary to lactose and galactose ingestion is present in certain subpopulations. In these population groups, the size of which is unknown, the lens could be exposed to intermittent episodes of hypergalactosemia due to the presence of a partial enzyme deficiency in the galactose metabolic pathway, and/or the persistence of a high adult jejunal lactase activity, and/or to a large and repeated consumption of either whole lactose or easily absorbed lactose (hydrolyzed forms and nonpasteurized yogurt). PMID- 1901326 TI - The effect of nursing home quality on patient outcome. AB - This historical cohort study investigated the relationship between nursing home quality and the group outcomes of mortality, rehospitalization, and discharge. Multiple logistic regression was used to determine if nursing home quality indices increased the prediction of these outcomes when patient severity of illness and case-mix differences were in the model. Three hundred ninety veterans discharged to 11 nursing homes were followed for 6 months. Nursing home quality was assessed using indices from the Multiphasic Environmental Assessment Procedure and the Rush-Medicus Methodology for Monitoring Quality of Nursing Care. An increased likelihood of death was associated with the diagnoses of cancer and heart disease and with being rehospitalized. Four nursing home quality indices significantly improved the prediction of mortality (RN hours, nursing process, security, and mean quality). Rehospitalization was associated with the patient factors of heart disease, hypertension, race, and level of care and with size of the nursing home. Discharge from the facility was inversely associated with the diagnosis of cancer and directly related to the index of nursing process. The results support the notion that group outcomes may be related to nursing home quality and suggest the need for further studies to investigate the specific elements of nursing home quality which relate to improved outcome. PMID- 1901327 TI - Care management. AGS Public Policy Committee. PMID- 1901328 TI - Quality of life nursing care. An experimental trial in long-term care. AB - The study supports the idea that institutionalized elders' quality of life can be enhanced without increasing the cost of nursing care. By increasing resident choice and control over daily activities, well-being is enhanced despite a declining health status. Staff attitudes toward resident control and choice can be positively affected by implementing the Quality of Life Nursing Care Model. PMID- 1901329 TI - Detection of apoptosis of immature CD4+8+ thymocytes by flow cytometry. AB - Apoptosis, i.e., programmed cell death, may be the mechanism by which both autoreactive and unselected immature CD4+8+ thymocytes are eliminated in the thymus. In the present paper we describe a simple and rapid flow cytometric method which permits one to study the induction and kinetics of apoptosis of CD4+8+ thymocytes using in vivo and in vitro suspension cultures. Analysing the level of surface expression of CD4 and CD8 molecules, forward light scatter and side (90 degrees) scatter as well as staining with ethidium bromide, three distinct stages of apoptosis of CD4+8+ thymocytes were defined. By counting cells passing through different stages of apoptosis one can attempt to quantitate this process. This method should be useful for in vitro studies on the mechanisms of negative and positive selection of CD4+8+ thymocytes, i.e., induction and inhibition of apoptosis respectively. PMID- 1901330 TI - Evidence for clonal spread of a single strain of beta-lactamase-producing Enterococcus (Streptococcus) faecalis to six hospitals in five states. AB - Beta-lactamase-producing (Bla+) enterococci have been reported in three state and two countries. Pulsed-field gel electrophoresis was used to compare 14 Bla+ Enterococcus (Streptococcus) faecalis isolated from hospitalized patients in seven states and three continents. The restriction endonuclease digestion patterns of isolates from Connecticut, Massachusetts, Lebanon, and Argentina were all markedly different, indicating that these were different strains. However, isolates from Delaware, Texas, Pennsylvania (Philadelphia and Pittsburgh), Florida, and Virginia were similar, indicating that these isolates were derivatives of a single strain. This conclusion was supported by hybridization using individual fragments as probes. Spread of Bla+ enterococci within the hospital setting was also demonstrated. These findings illustrate the value of pulsed-field gel electrophoresis for epidemiologic analyses and support the importance of identifying and containing organisms with new resistance properties in an effort to decrease their transmission to and from, as well as within, hospitals. PMID- 1901331 TI - Differences of pathophysiology in experimental meningitis caused by three strains of Streptococcus pneumoniae. AB - Differences in cytochemical and pathophysiologic abnormalities in experimental meningitis caused by pneumococcal strains A, B, and C were determined. Strain C produced the most severe abnormalities of cerebrospinal fluid (CSF) concentrations of lactate (P less than .01), protein (P less than .02), and glucose (P less than .01), CSF white blood cell count (P less than .04), cerebral blood flow (P less than .02), and clinical signs (P less than .05). Brain edema occurred only with strains A anc C, with no association with disease severity; intracranial hypertension was also independent of disease severity. Strain B, not C, achieved the highest bacterial titers in the CSF (P less than .005). The widely different abilities of strains of Streptococcus pneumoniae to induce intracranial abnormalities suggest that virulence determinants affect not only evasion of defense during colonization and invasion, as shown in other models, but also determine the course of disease once infection has been established. Differences of cell-wall metabolism among pneumococcal strains may play a role in this latter phase of the development of meningitis. PMID- 1901332 TI - In vivo interferon-gamma therapy augments the in vitro ability of chronic granulomatous disease neutrophils to damage Aspergillus hyphae. AB - During the recently completed double-blind, placebo-controlled, randomized trial of recombinant interferon-gamma (rIFN-gamma) therapy in chronic granulomatous disease (CGD), a metabolic assay of neutrophil damage to Aspergillus fumigatus hyphae was used to monitor neutrophil function before and during therapy. In this assay, 5 x 10(4) conidia that had germinated into hyphae were exposed to 5 x 10(5), 15 x 10(5), or 50 x 10(5) CGD neutrophils. By analysis of variance, neutrophils from patients on rIFN-gamma were found to produce significantly more damage to hyphae than those from the placebo group (P less than .01). In subgroup analysis, this effect was best seen in the hyphae exposed to 50 x 10(5) CGD neutrophils, where neutrophils from patients receiving rIFN-gamma produced significantly more damage to the hyphae than those from the placebo group (P less than .05). In vivo rIFN-gamma therapy improves the ability of CGD neutrophils to damage Aspergillus fumigatus hyphae in an in vitro assay. PMID- 1901334 TI - Prevaccination serologic screening for measles in health care workers. AB - A model was developed from which the cost-effectiveness of prevaccination serologic screening for measles could be estimated, for any combination of antibody screening costs and prevalence of antibody to measles. This model was tested using sera obtained prospectively from 222 health care workers, including 181 born in or after 1957 who had no history of measles, no measles vaccine after 1980, and no documentation of immunity to measles. In addition, 41 subjects born before 1957 who had no history of measles were studied. A rapid, reliable, and inexpensive ($5 per test) commercial ELISA was used to test for antibodies to measles; its seroprevalence in the subject population was 86%. From the model, it was estimated that prevaccination serologic testing would be cost-effective if antibody screening cost less than or equal to $12.75 per test. In this subject population, prevaccination serologic screening for measles was cost-effective. PMID- 1901333 TI - Tumor necrosis factor (cachectin) in human visceral leishmaniasis. AB - High tumor necrosis factor-alpha (TNF alpha) levels were present in the serum of 24 of 28 active visceral leishmaniasis (VL) patients (142.9 +/- 113.9 pg/ml, mean +/- SD), whereas levels were not elevated in 26 of 30 patients with cryptic leishmanial infection (16 asymptomatic, 4 with self-healing subclinical infection, and 10 posttreatment VL cases). Serum TNF alpha levels were also not elevated in 15 normal volunteers (11.3 +/- 15.6 pg/ml) and in 10 patients with tegumentary leishmaniasis (19.1 +/- 10.8 pg/ml). Leishmanial infection of human monocyte-derived macrophages enhanced the basal TNF alpha production by these cells, and this effect was further potentiated by treatment with recombinant interferon-gamma. After effective treatment of VL patients, serum TNF alpha levels dropped rapidly (129 +/- 112 vs. 9 +/- 13 pg/ml in 10 days), even before clinical parameters such as spleen size or parasitism, white blood cell count, or levels of hemoglobin returned to normal values. On the other hand, patients unresponsive to treatment remained with elevated levels (276 +/- 69 vs. 155 +/- 71 pg/ml in 10 days). Thus, serum TNF alpha levels in VL patients are a good parameter to monitor in determining host response to therapy. PMID- 1901335 TI - Neutralizing antibodies to interferon-alpha: relative frequency in patients treated with different interferon preparations. AB - The frequencies of antibody development so far reported in patients treated with different interferons (IFNs) are not readily comparable because of differences in treatment regimens and assay methods. Thus the frequency of neutralizing antibody development was analyzed in a large sample of sera derived from a relatively homogeneous group of patients treated with different IFN-alpha preparations. The frequency of developing neutralizing antibody to IFN varied according to the IFN given. Particularly, the seroconversion frequency was significantly higher in patients treated with recombinant IFN-alpha 2a (20.2%) than in patients treated with either recombinant IFN-alpha 2b (6.9%) or IFN-alpha N1 (1.2%), a lymphoblastoid IFN-alpha. Furthermore, sera obtained from patients treated with either recombinant IFN neutralized both types of recombinant IFNs but failed to neutralize IFN-alpha N1. PMID- 1901336 TI - Recombinant human interferon-gamma as adjunct therapy for Aspergillus infection in a patient with chronic granulomatous disease. AB - The hallmark of chronic granulomatous disease (CGD) is defective killing of ingested microorganisms by phagocytic cells. Invasive aspergillosis in CGD patients is particularly virulent and has a mortality rate of approximately 50%. A patient with autosomal recessive CGD was identified who had progressive pulmonary aspergillosis that was unresponsive to conventional antifungal therapy. She was treated with recombinant human interferon-gamma (rHuIFN-gamma) and had a dramatic improvement in clinical symptoms, sedimentation rate, and radiographic scans. No consistent improvement in bactericidal function or neutrophil oxidative capacity could be demonstrated. However, serum neopterin levels, a measure of macrophage activation, increased in a dose-dependent manner with rHuIFN-gamma therapy; increased levels mirrored the improved clinical parameters. This patient's treatment illustrates the usefulness of the single-photon emission computed tomography (SPECT) gallium scan for following pulmonary inflammatory lesions in the presence of fibrosis and indicates that rHuIFN-gamma may be of benefit to CGD patients with serious infections unresponsive to conventional therapy. PMID- 1901337 TI - Endogenous interferon-gamma, macrophage activation, and murine host defense against acute infection with Trypanosoma cruzi. AB - Parenteral interferon-gamma (IFN-gamma) activates murine macrophages to inhibit Trypanosoma cruzi multiplication and diminishes parasitemia and mortality in acute infection. To investigate the role of endogenous IFN-gamma in acute infection, monoclonal antibody to IFN-gamma was injected intraperitoneally into mice. The 6250 neutralizing units given 24 and 96 h after infection reproducibly increased mortality (P less than .05). Histology sections showed markedly more nests of T. cruzi in treated mice. BALB/c, Swiss Webster, C57Bl/6, and C3H/HEN mice were susceptible to the effects of anti-IFN-gamma. Peritoneal macrophages from mice 4 days after infection and a single dose of 6250 units of anti-IFN gamma had significantly reduced ability to inhibit T. cruzi multiplication. Multiple doses of anti-IFN-gamma delayed but did not prevent macrophage activation. These results indicate the critical role of endogenous IFN-gamma for macrophage activation and host defense against acute T. cruzi infection in mice. PMID- 1901338 TI - Human neutrophils, activated with cytokines or not, do not kill virulent Mycobacterium tuberculosis. PMID- 1901339 TI - Neonatal listeriosis due to cross-infection confirmed by isoenzyme typing and DNA fingerprinting. PMID- 1901340 TI - Is plasma dopa a valid indicator of sympathetic activity? PMID- 1901341 TI - Increased plasma dihydroxyphenylalanine during sympathetic activation in humans is related to increased norepinephrine turnover. AB - Plasma concentrations of dihydroxyphenylalanine (DOPA) were measured before and during isometric handgrip exercise or mental stress and after coffee drinking or intravenous infusion of desipramine to examine the influence of sympathetic nervous activity on DOPA formation. Sympathetic activity was assessed by the spillover of norepinephrine into plasma. Turnover of norepinephrine was assessed by the plasma concentration of its intraneuronal metabolite, dihydroxyphenylglycol (DHPG). In normal subjects the resting plasma concentration of DOPA was 6.05 +/- 0.16 nmol/L (n = 42). Plasma DOPA level was increased by stimulation of the sympathetic nervous system; handgrip exercise caused a 0.49 +/ 0.07 nmol/L increase (n = 15), mental stress a 0.25 +/- 0.10 nmol/L increase (n = 34), and coffee drinking a 0.85 +/- 0.19 nmol/L increase (n = 9). Desipramine decreased plasma DOPA level by 0.25 +/- 0.06 nmol/L (n = 23). The small but consistent changes in plasma DOPA level during manipulations of sympathetic activity were positively correlated with changes in norepinephrine spillover (r = 0.55, n = 81) and plasma DHPG level (r = 0.66, n = 81). Percentage increases in plasma DOPA level during sympathetic activation were similar to those in plasma DHPG but were a sixth of the percentage increases in norepinephrine spillover. The similar increases in plasma DOPA and DHPG levels indicated that production of DOPA was related to the turnover of norepinephrine in sympathetic nerves. The smaller percentage increases in plasma DOPA (smaller than those in norepinephrine spillover) were consistent with the partial contribution of exocytotic neurotransmitter release to the turnover of norepinephrine in sympathetic nerves. PMID- 1901343 TI - Defenses against oxidation in human erythrocytes: role of glutathione reductase in the activation of glucose decarboxylation by hemolytic drugs. AB - We have used 1,3-bis(2-chloroethyl)-1-nitrosourea, a selective inhibitor of oxidized glutathione reductase (GSSG-R), to examine the role of this enzyme in regulating the hexose monophosphate shunt (HMS) and to explore how a variety of agents influence glucose decarboxylation in intact human red blood cells (RBCs). Substances tested included primaquine and several other drugs that are specially hemolytic and methemoglobinemic in glucose-6-phosphate dehydrogenase (G6PD) deficiency and related disorders. The results allowed us to distinguish and quantitate contrasting modes of HMS stimulation and to clarify how RBCs respond to different classes of oxidants. Some agents like methylene blue (MB), phenazine methosulfate, and pyrroline carboxylate do not require GSSG-R to increase CO2 production; they activate G6PD and 6-phosphogluconic dehydrogenase by directly oxidizing reduced nicotinamide adenine dinucleotide phosphate (NADPH) to oxidized nicotinamide adenine dinucleotide phosphate (NADP). Other compounds, like ascorbate, nitrofurantoin, and doxorubicin, oxidize GSH primarily; CO2 increases indirectly only when GSSG-R, activated by glutathione disulfide (GSSG), raises the level of NADP. Chemicals like primaquine, daunorubicin, and methylphenylazoformate trigger the HMS by independently oxidizing both NADPH and GSH. Unlike MB, most drugs that are hemolytic in G6PD deficiency activate the HMS in a manner that depends to a variable extent on GSSG-R. This variability may explain hitherto puzzling clinical and pharmacogenetic differences between primaquine and diaminodiphenylsulfone-induced hemolysis. PMID- 1901342 TI - Thrombin-induced leukopenia and thrombocytopenia are attenuated by PAF antagonist WEB 2086. AB - Thrombin has been shown to increase pulmonary transvascular permeability in vivo. This permeability change appears to be dependent on polymorphonuclear leukocytes (PMNs). In vitro, thrombin has been demonstrated to increase PMN adherence to endothelial cells coincident with generation of platelet activating factor (PAF) by endothelial cells. These observations have led to the suggestion that PAF mediates, in part, the attachment of PMNs to endothelial cells. We examined this hypothesis in vivo and in vitro with a specific PAF receptor antagonist, WEB 2086. Prior infusion of WEB 2086 into conscious sheep significantly attenuated the drop in peripheral blood PMN counts observed during and after infusion of alpha-thrombin (30 NIH U/kg). These data suggest that WEB 2086 prevented PMN margination on endothelial cells. WEB 2086 also attenuated the thrombocytopenia seen after thrombin infusion and ameliorated the thrombin-induced hypoxemia and hemoconcentration. WEB 2086 did not affect the thrombin-induced hemodynamic response, the degree of intravascular coagulation as assessed by fibrin degradation product generation, or thromboxane B2 generation. In vitro, WEB 2086 prevented the augmented adherence of sheep PMNs to sheep endothelial cell monolayers after thrombin stimulation. The results of the present study are consistent with the hypothesis that PAF mediates, at least in part, thrombin induced leukopenia and thrombocytopenia in vivo. PMID- 1901344 TI - Lipoxygenase-mediated transformation of human low density lipoprotein to an oxidized and cytotoxic complex. AB - We have been studying the mechanisms involved in the oxidative modification of low density lipoprotein (LDL) that lead to its transformation to a cytotoxic complex. Here we examine the direct effect-of soybean lipoxygenase (SLO), a 15 lipoxygenase, on normal human LDL. SLO oxidized LDL and rendered it cytotoxic; agents known to interfere with lipoxygenase activity inhibited this reaction. Enhancement of both the SLO-mediated LDL oxidation and the conversion of LDL to a cytotoxin was observed when either superoxide dismutase or copper (II) (3,5, diisopropylsalicylic acid)2, both of which dismute superoxide anion, were included during the incubation of SLO with LDL. In contrast, catalase inhibited this reaction in the presence or absence of agents that dismute superoxide anion. Thus, purified lipoxygenase can mediate LDL modification and superoxide anion inhibits this reaction, Furthermore, H2O2 is essential for SLO-mediated LDL oxidation and conversion of LDL to a cytotoxin. PMID- 1901345 TI - Isolation and characterization of an apoA-II-containing lipoprotein (LP-A-II:B complex) from plasma very low density lipoproteins of patients with Tangier disease and type V hyperlipoproteinemia. AB - Previous studies have shown that very low density lipoproteins (VLDL) from patients with Tangier disease are less effective as a substrate for human milk lipoprotein lipase (LPL) than VLDL from normal controls as assessed by measuring the first order rate constant (k1) of triglyceride hydrolysis. Tangier VLDL also has a higher content of apolipoprotein (apo) A-II than normal VLDL. To explore the possible relationship between the relatively high concentration of apoA-II in VLDL and low k1 values, Tangier VLDL were fractionated on an anti-apoA-II immunosorber. The retained fraction contained a newly identified triglyceride rich lipoprotein characterized by the presence of apolipoproteins A-II, B, C-I, C II, C-III, D, and E (LP-A-II:B:C:D:E or LP-A-II:B complex), whereas the unretained fraction consisted of previously identified triglyceride-rich apoB containing lipoproteins free of apoA-II. In VLDL from patients with Tangier disease or type V hyperlipoproteinemia, the LP-A-II:B complex accounted for 70 90% and 25-70% of the total apoB content, respectively. The LP-A-II:B complexes had similar lipid and apolipoprotein composition; they were poor substrates for LPL as indicated by their low k1 values (0.014-0.016 min-1). In contrast, the apoA-II-free lipoproteins present in unretained fractions were effective substrates for LPL with k1 values equal to or greater than 0.0313 min-1. These results indicate that triglyceride-rich lipoproteins consist of several apoB containing lipoproteins, including the LP-A-II:B complex, and that lipoprotein particles of similar size and density but distinct apolipoprotein composition also possess distinct metabolic properties. PMID- 1901346 TI - Structural and functional properties of reconstituted high density lipoprotein discs prepared with six apolipoprotein A-I variants. AB - Six apolipoprotein A-I (apoA-I) variants containing the following amino acid changes: Pro3----Arg, Pro4----Arg, Lys107----0 (Lys deletion) Lys107----Met, Pro165----Arg, and Glu198----Lys, and the corresponding normal allele products, were isolated by preparative isoelectric focusing from heterozygous individuals. The apoA-I samples were reconstituted with palmitoyloleoyl phosphatidylcholine (POPC) or dipalmitoyl phosphatidylcholine (DPPC), and small amounts of cholesterol, into discoidal high density lipoprotein (HDL) complexes in order to examine their lipid binding and structural properties as well as their ability to activate lecithin:cholesterol acyltransferase (LCAT). Starting with initial molar ratios around 100:5:1 for phosphatidylcholine-cholesterol-apolipoprotein, all the normal and variant apoA-Is were completely incorporated into reconstituted HDL (rHDL). The rHDL particle sizes and their distributions were examined by nondenaturing gradient gel electrophoresis, before and after incubation with LDL, to assess the folding of apoA-I in the complexes. Intrinsic Trp fluorescence properties of the rHDL were measured, as a function of temperature and guanidine hydrochloride concentration, to detect conformational differences in the apoA-I variants. In addition, the LCAT reaction kinetics were measured with all the rHDL, and the apparent kinetic constants were compared. In terms of the structure of the rHDL particles, all the normal variant apoA-Is had similar sizes (94, 96 A) and size distributions, and indistinguishable fluorescence properties, with the exception of the Lys107----0 mutant. This variant formed slightly larger particles that were resistant to rearrangements in the presence of LDL, and had an altered apoA-I conformation in the vicinity of the Trp residues. The kinetic experiments with LCAT indicated that the apoA-I variants, Lys107----0 and Pro165- --Arg, in rHDL particles had statistically different (30 to 90%) kinetic constants from the corresponding normal allele products; however, the variability in the kinetic constants among the normal apoA-I products was even greater (40 to 430%). Therefore, we conclude that the effects of these six mutations in apoA-I on the activation of LCAT are minor, and that the structural effects on rHDL, and possibly native HDL, are insignificant with the exception of the Lys107----0 mutation. PMID- 1901347 TI - The nigrostriatal dopaminergic pathway in Wilson's disease studied with positron emission tomography. AB - Movement disorders, including Parkinsonism, are prominent features of neurological Wilson's disease (WD). This suggests there may be dysfunction of the nigrostriatal dopaminergic pathway. To explore this possibility, five patients were studied using positron emission tomography (PET) with 18F-6-fluorodopa (6FD), and magnetic resonance imaging (MRI). We calculated striatal 6FD uptake rate constants by a graphical method and compared the results with those of 18 normal subjects. It was found that four patients with symptoms all had abnormally low 6FD uptake, and the one asymptomatic patient had normal uptake. PET evidence for nigrostriatal dopaminergic dysfunction was present even after many years of penicillamine treatment. It is concluded that the nigrostriatal dopaminergic pathway is involved in neurological WD. PMID- 1901348 TI - Treatment of Guillain-Barre syndrome with anti-T cell monoclonal antibodies. AB - Three patients with acute Guillain-Barre syndrome were treated early in the course of the disease with OKT3, an anti-T-cell monoclonal antibody. Each patient developed acute lymphopenia with specific depletion of T3-positive lymphocytes. Two patients had continued progression of clinical deficits for eight and 14 days. This suggests that T lymphocytes may not be essential for progression of Guillain-Barre syndrome at this stage of the disease. PMID- 1901349 TI - Recombinant tissue plasminogen activator in two patients with basilar artery occlusion. AB - Two patients with angiographically proved basilar artery occlusion were treated with systemic recombinant tissue plasminogen activator (rtPA) according to protocol. The first patient was in a locked-in state and gradually deteriorated. On repeat angiography the basilar artery remained occluded. He died and necropsy revealed a pontine haemorrhagic infarction. The second patient, who was comatose and with decerebrate posturing, made a remarkable recovery. Angiography showed reperfusion. Therapy was initiated in the first patient after six hours and in the second after two hours. Treatment with rtPA is promising but probably not feasible for every patient. Success may depend on duration of occlusion and composition of occluding thrombus. PMID- 1901350 TI - Hyperphagia in dementia: fluvoxamine takes the biscuit. PMID- 1901351 TI - Pituitary hormones in relation to magnetic stimulation of the brain. PMID- 1901352 TI - Atypical meningitis complicating a penetrating head injury. PMID- 1901353 TI - Growth cone distribution patterns in the optic nerve of fetal monkeys: implications for mechanisms of axon guidance. AB - The distribution of growth cones was studied in the optic nerve of monkeys during the first half of prenatal development using quantitative electron microscopic methods. Our aim was to test the hypothesis that ganglion cell growth cones extend predominantly along the surfaces of the nerve, just beneath the pia mater. A complete census of growth cones in cross sections of the nerve during the early phase of axon ingrowth, from embryonic day 39 (E39) to E41, demonstrates that growth cones are scattered within the majority of fascicles, even those located far from the surface of the nerve. By E45, growth cones are concentrated around the nasal, dorsal, and ventral edge of the optic nerve. They are less concentrated in the core and around the temporal edge. However, even as late as E49, virtually all fascicles in the nerve, whether deep or superficial, contain growth cones. Growth cones are dispersed within single fascicles and are often located far from glia. Thus, the newest fibers penetrate deep parts of the pathway and push through centers of densely packed bundles of older axons. This finding is consistent with the vagrant paths of growing axons reported in previous work on embryonic monkey optic nerve (Williams and Rakic, 1985). Our data challenge the hypotheses that growth cones extend selectively along the basal lamina, the pia mater, or glial end feet. Gradients found at later stages of development in the nerve are not due to a particular affinity of growth cones for non-neuronal substrata. The pattern we observed is much more likely to result from central-to-peripheral gradients in ganglion cell generation and possible associations between growth cones originating from the same regions of the retina. PMID- 1901354 TI - Inflammation near the nerve cell body enhances axonal regeneration. AB - Although crushed axons in a dorsal spinal root normally regenerate more slowly than peripheral axons, their regeneration can be accelerated by a conditioning lesion to the corresponding peripheral nerve. These and other observations indicate that injury to peripheral sensory axons triggers changes in their nerve cell bodies that contribute to axonal regeneration. To investigate mechanisms of activating nerve cell bodies, an inflammatory reaction was provoked in rat dorsal root ganglia (DRG) through injection of Corynebacterium parvum. This inflammation enhanced regeneration in the associated dorsal root, increasing 4-fold the number of regenerating fibers 17 d after crushing; peripheral nerve regeneration was not accelerated. A milder stimulation of dorsal root regeneration was detected after direct injection of isogenous macrophages into the ganglion. It is concluded that changes favorable to axonal regeneration can be induced by products of inflammatory cells acting in the vicinity of the nerve cell body. Satellite glial cells and other unidentified cells in lumbar DRG were shown by thymidine radioautography to proliferate after sciatic nerve transection or injection of C. parvum into the ganglia. Intrathecal infusion of mitomycin C suppressed axotomy induced mitosis of satellite glial cells but did not impede axonal regeneration in the dorsal root or the peripheral nerve. Nevertheless, the similarity in reactions of satellite glial cells during 2 processes that activate neurons adds indirect support to the idea that non-neuronal cells in the DRG might influence regenerative responses of primary sensory neurons. PMID- 1901355 TI - Nursing case management. Does it pay? AB - Hospitals can realize substantial savings from nursing case management. The author describes an investigation assessing the cost-effectiveness of this mode of patient care delivery. The results showed an overall decrease in length of stay, an increase in patient turnover, and a potential increase in patient revenues generated for the hospital. The author provides several general and socioeconomic implications relating to the importance of nursing case management to patient care and institutions' profitability. PMID- 1901356 TI - Cartilage synthesizes the serine protease inhibitor PAI-1: support for the involvement of serine proteases in cartilage remodeling. AB - The work described here demonstrates the synthesis by human articular cartilage of plasminogen activator inhibitor-1 (PAI-1), a potent inhibitor of the serine protease tissue plasminogen activator (tPA). We also present data demonstrating an increase in PAI-1 messenger ribonucleic acid (mRNA) in chondrocytes exposed to the cytokine interleukin-1 (IL-1). Interestingly, this elevation of steady-state mRNA levels does not appear to result in an increase in synthesis of PAI-1 protein. Northern blot analysis reveals that of the two mRNA species (3.4 kb, 2.4 kb) previously reported for PAI-1, only the larger species (3.4 kb) appears to be synthesized by chondrocytes. Our data demonstrate the IL-1-stimulated production by cartilage of tissue plasminogen activator. We also show evidence for the presence of plasminogen in cartilage. A scheme is presented indicating the probable importance of the serine proteases (tPA and plasminogen) and PAI-1 in cartilage degradation. PMID- 1901357 TI - Effect of extracellular fatty acids on lipid metabolism in cultured rabbit articular chondrocytes. AB - Rabbit articular chondrocytes were cultured for 8 h in the presence of various concentrations (5-500 microM) of [14C] oleic, [14C] linoleic, and [3H] arachidonic acids. The radioactive unsaturated fatty acids were incorporated into triacylglycerol (TG) and phosphatidylcholine (PC) in a concentration-dependent manner; more fatty acids were incorporated into TG than into PC, at higher concentrations of extracellular fatty acids. Among these fatty acids, arachidonic acid was incorporated into TG much more than into PC, in spite of a very low concentration of arachidonic acid in TG. After transfer of the labeled cells to maintenance medium, the radioactivity in TG declined rapidly and [3H] arachidonic acid radioactivity in PC increased continuously during the chase time periods. Palmitoyl-unsaturated species were mainly formed in PC when cultured at a concentration of 5 microM of each fatty acid. However, when cultured at 500 microM, unsaturated-unsaturated species, specific for each unsaturated fatty acid were actively formed. These findings indicate that (1) fatty acid composition of TG and PC in articular chondrocytes is influenced by the degree of fatty acid supply, (2) formation and turnover of TG plays a role in fatty acid metabolism of cells, and (3) fatty acid pairing in PC is modulated by extracellular fatty acid concentrations. PMID- 1901358 TI - Avian hematozoa from west-central Bolivia. AB - A total of 641 birds representing 135 species of 25 families from Noel Kempff Mercado National Park in west-central Bolivia was examined for hematozoa; only 33 (5.1%) harbored blood parasites. Microfilariae were the most commonly encountered hematozoans, followed, in numerical sequence, by species of Haemoproteus and Plasmodium; Trypanosoma, Atoxoplasma, and Hepatozoon were seen infrequently. The survey included 13 new host-parasite records, and 58 species of birds were examined for blood parasites for the first time; 43 were parasite-free. The low prevalence of parasitism recorded in this survey is compared to other areas in the Neotropical region and to prevalence of blood parasites in the avifauna of other major land masses. PMID- 1901359 TI - Sarcocystis neurona n. sp. (Protozoa: Apicomplexa), the etiologic agent of equine protozoal myeloencephalitis. AB - Sarcocystis neuronan n. sp. is proposed for the apicomplexan taxon associated with myeloencephalitis in horses. Only asexual stages of this parasite presently are known, and they are found within neuronal cells and leukocytes of the brain and spinal cord. The parasite is located in the host cell cytoplasm, does not have a parasitophorous vacuole, and divides by endopolygeny. Schizonts are 5-35 microns x 5-20 microns and contain 4-40 merozoites arranged in a rosette around a prominent residual body. Merozoites are approximately 4 x 1 micron, have a central nucleus, and lack rhoptries. Schizonts and merozoites react with Sarcocystis cruzi antiserum but not with Caryospora bigenetica. Toxoplasma gondii, Hammondia hammondi, or Neospora caninum antisera in an immunohistochemical test. PMID- 1901360 TI - Uptake and effect of praziquantel and the major human oxidative metabolite, 4 hydroxypraziquantel, by Schistosoma japonicum. AB - After exposure to praziquantel in vitro at a concentration of 1 microgram/ml for 0.5-2 hr, amounts of praziquantel in Schistosoma japonicum varied from 2.1 +/- 1.2 to 3.7 +/- 1.6 ng/male worm and 1.3 +/- 1.2 to 2.2 +/- 1.5 ng/female worm during the time studied. At 30 micrograms/ml, praziquantel amounts were 11-33 fold higher. However, within 2 hr after removal from a medium containing 30 micrograms/ml praziquantel, 95% of the drug was released from the parasites. When S. japonicum worm pairs were incubated in vitro with 1, 10, and 30 micrograms/ml of 4-hydroxypraziquantel, the major human oxidative metabolite of praziquantel, 0.2 +/- 0.2, 3.8 +/- 1.3, and 7.4 +/- 1.3 ng/worm pair, respectively, were found after a 2-hr incubation. 15-30-fold lower than corresponding worm pair amounts of praziquantel. In vivo, when 4- or 5-wk S. japonicum-infected mice were treated orally with praziquantel (300 mg/kg), peak concentrations of praziquantel in plasma determined by high pressure liquid chromatography were 14.7 +/- 1.5 micrograms/ml (4-wk infection) and 16.7 +/- 2.8 micrograms/ml (5-wk infection) 15 min after treatment. Corresponding in vivo worm praziquantel amounts were 1.8 +/- 0.4 ng/male worm and 2.4 +/- 1.1 ng/female worm, respectively, in the 4-wk infection and 4.6 +/- 1.6 ng/male worm and 5.6 +/- 1.2 ng/female worm in the 5-wk infection. Peak plasma concentrations of 4-hydroxypraziquantel were similar but corresponding in vivo worm amounts were 1-20-fold lower, depending on the time after drug administration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1901361 TI - Production and characterisation of monoclonal antibodies to outer-membrane protein antigens of Vibrio cholerae O1. AB - Monoclonal antibodies (MAbs) were raised against the major, 46-48-Kda outer membrane proteins of Vibrio cholerae O1. The hybridoma clones were screened by enzyme-linked immunosorbent assay (ELISA) with cell-surface proteins of V. cholerae O1 as the coating antigen. Four hybridomas, which secreted anti-V. cholerae cell-surface-protein antibodies, were subcloned by limiting dilution and obtained as ascites in vivo. A MAb of the IgG1 subclass was isolated in good yield from the murine ascites by affinity chromatography with recombinant protein G-Sepharose 4B. It gave positive reactions, as determined by ELISA, against cell surface proteins prepared from both biotypes (classical and El Tor) and both serotypes (Ogawa and Inaba) of V. cholerae O1. The MAb did not have any reactivity towards V. cholerae lipopolysaccharide preparations. Immunoblotting studies were performed on cell-surface proteins separated by one-dimensional sodium dodecyl sulphate-polyacrylamide gel electrophoresis (1D SDS-PAGE) and also by two-dimensional (2D) electrophoresis with iso-electric focusing in the first dimension followed by SDS-PAGE in the second dimension. When proteins were separated by 1D SDS-PAGE, only one band at 46-48 Kda reacted with the MAb. This protein appeared to consist of two narrowly-spaced and cross-reactive bands when a nitrocellulose blot, obtained by 2D SDS-PAGE, was exposed to the MAb. PMID- 1901362 TI - Crystals of Anabaena PCC 7119 ferredoxin-NADP+ reductase. AB - Crystals of ferredoxin-NADP+ reductase (FNR) from the cyanobacterium Anabaena PCC 7119 are grown in the presence of polyethylene glycol 6000 and beta-octyl glucoside. They belong to the hexagonal system. The cell parameters are a = b = 87.8 A, c = 92.7 A, space group P6(1) or P6(5), and a Vm of 3.0 A3/dalton for one molecule of 36,000 daltons per asymmetric unit. These crystals diffract strongly up to 1.9 A and are suitable for X-ray structural studies. PMID- 1901363 TI - X-ray crystal structure of the two site-specific mutants His35Gln and His35Leu of azurin from Pseudomonas aeruginosa. AB - The three-dimensional structures of two site-specific mutants of the blue copper protein azurin from Pseudomonas aeruginosa have been solved by a combination of isomorphous replacement and Patterson search techniques, and refined by energy restrained least-squares methods. The mutations introduced by recombinant DNA techniques involve residue His35, which was exchanged for glutamine and leucine, to probe for its suggested role in electron transfer. The two mutants, His35Gln (H35Q) and His35Leu (H35L), crystallize non-isomorphously in the orthorhombic space group P2(1)2(1)2(1) with unit cell dimensions of a = 109.74 A, b = 99.15 A, c = 47.82 A for H35Q, a = 57.82 A, b = 81.06 A, c = 110.03 A for H35L. In each crystal form, there are four molecules in the asymmetric unit. They are arranged as a dimer of dimers in the H35Q case and are distorted from ideal C2 symmetry in H35L. The final crystallographic R-value is 16.3% for 20.747 reflections to a resolution of 2.1 A for H35Q and 17.0% for 32,548 reflections to 1.9 A for H35L. The crystal structures reported here represent the first crystallographically refined structures for azurin from P. aeruginosa. The structure is very similar to that of azurin from Alcaligenes denitrificans. The copper atom is located about 7 A below a hydrophobic surface region and is ligated by five donor groups in a distorted trigonal bipyramidal fashion. The implications for electron transfer properties of the protein are discussed in terms of the mutation site and the packing of the molecules within the tetramer. PMID- 1901364 TI - Molecular evolution of hemagglutinin genes of H1N1 swine and human influenza A viruses. AB - The hemagglutinin (HA) genes of influenza type A (H1N1) viruses isolated from swine were cloned into plasmid vectors and their nucleotide sequences were determined. A phylogenetic tree for the HA genes of swine and human influenza viruses was constructed by the neighbor-joining method. It showed that the divergence between swine and human HA genes might have occurred around 1905. The estimated rates of synonymous (silent) substitutions for swine and human influenza viruses were almost the same. For both viruses, the rate of synonymous substitution was much higher than that of nonsynonymous (amino acid altering) substitution. It is the case even for only the antigenic sites of the HA. This feature is consistent with the neutral theory of molecular evolution. The rate of nonsynonymous substitution for human influenza viruses was three times the rate for swine influenza viruses. In particular, nonsynonymous substitutions at antigenic sites occurred less frequently in swine than in humans. The difference in the rate of nonsynonymous substitution between swine and human influenza viruses can be explained by the different degrees of functional constraint operating on the amino acid sequence of the HA in both hosts. PMID- 1901365 TI - There appear to be conserved constraints on the distribution of nucleotide sequences in cellular genomes. AB - The data from a genomic library can be sorted into the frequencies of every possible tetranucleotide in the sequence. This tabulation, a short sequence distribution, contains the frequency of occurrence of the 256 tetranucleotides and thus seems to serve as a vehicle for averaging sequence information. Two such distributions can be readily compared by correlation. Reported here are correlations (Spearman rs) of the distributions from all of the genomic libraries in GenBank 44.0 with sizes equal to or larger than that of Salmonella typhimurium, except for the data for mouse and humans. All of the organisms examined showed highly significant correlations between the two DNA strands (not the complementarity expected from base pairing). Of 155 comparisons between libraries, 132 showed significant correlations at the 99% confidence level. Application of the correlation coefficients as a similarity matrix clustered most organisms in a phenogram in a pattern consistent with other hypotheses. This suggests a highly conserved pattern underlying all other genetic information in cellular DNA and affecting both DNA strands, perhaps caused by interaction with conserved factors necessary for DNA packaging. PMID- 1901366 TI - Highly repetitive DNA sequence in parthenogenetic Artemia. AB - The study of the structural organization of the eukaryotic genome is one of the most important tools for disclosing the evolutionary relationships between species. Artemia (Crustacea, Phyllopoda) offers a very interesting model for speciation studies. The genus, distributed all over the world, comprises both bisexual sibling species and parthenogenetic populations, exhibiting different chromosome numbers (diploidy, polyploidy, and heteroploidy). Digestion of genomic DNA of the parthenogenetic Artemia sp. from Tsing-Tao (China) with the restriction enzymes Eco RI and Alu I reveals that a highly repetitive sequence of 133 bp is present. The Eco RI fragment has been cloned and characterized by genomic organization. The distribution of the Eco RI family of repeats was also studied in several bisexual and parthenogenetic Artemia populations and compared with an Alu I repetitive fragment previously identified in Artemia franciscana. PMID- 1901367 TI - Time of the deepest root for polymorphism in human mitochondrial DNA. AB - A molecular clock analysis was carried out on the nucleotide sequences of parts of the major noncoding region of mitochondrial DNA (mtDNA) from the major geographic populations of humans. Dates of branchings in the mtDNA tree among humans were estimated with an improved maximum likelihood method. Two species of chimpanzees were used as an outgroup, and the mtDNA clock was calibrated by assuming that the chimpanzee/human split occurred 4 million years ago, following our earlier works. A model of homogeneous evolution among sites does not fit well with the data even within hypervariable segments, and hence an additional parameter that represents a proportion of variable sites was introduced. Taking account of this heterogeneity among sites, the date for the deepest root of the mtDNA tree among humans was estimated to be 280,000 +/- 50,000 years old (+/- 1 SE), although there remains uncertainty about the constancy of the evolutionary rate among lineages. The evolutionary rate of the most rapidly evolving sites in mtDNA was estimated to be more than 100 times greater than that of a nuclear pseudogene. PMID- 1901369 TI - Codon usage divergence of homologous vertebrate genes and codon usage clock. AB - This paper is concerned with the divergence of synonymous codon usage and its bias in three homologous genes within vertebrate species. Genetic distances among species are described in terms of synonymous codon usage divergence and the correlation is found between the genetic distances and taxonomic distances among species under study. A codon usage clock is reported in alpha-globin and beta globin. A method is developed to define the synonymous codon preference bias and it is observed that the bias changes considerably among species. PMID- 1901368 TI - A molecular phylogeny of dinoflagellate protists (pyrrhophyta) inferred from the sequence of 24S rRNA divergent domains D1 and D8. AB - The sequence of two divergent domains (D1 and D8) from dinoflagellate 24S large subunit rRNA was determined by primer extension using total RNA as template. Nucleotide sequence alignments over 401 bases have been analyzed in order to investigate phylogenetic relationships within this highly divergent and taxonomically controversial group of protists of the division Pyrrhophyta. Data are provided confirming that dinoflagellates represent a monophyletic group. For 11 out of the 13 investigated laboratory grown species, an additional domain (D2) could not be completely sequenced by reverse transcription because of a hidden break located near its 3'-terminus. Two sets of sequence alignments were used to infer dinoflagellate phylogeny. The first [199 nucleotides (nt)] included conservative sequences flanking the D1 and D8 divergent domains. It was used to reconstruct a broad evolutionary tree for the dinoflagellates, which was rooted using Tetrahymena thermophila as the outgroup. To confirm the tree topology, and mainly the branchings leading to closely related species, a second alignment (401 nt) was considered, which included the D1 and D8 variable sequences in addition to the more conserved flanking regions. Species that showed sequence similarities with other species lower than 60% on average (Knuc values higher than 0.550) were removed from this analysis. A coherent and convincing evolutionary pattern was obtained for the dinoflagellates, also confirmed by the position of the hidden break within the D2 domain, which appears to be group specific. The reconstructed phylogeny indicates that the early emergence of Oxyrrhis marina preceded that of most Peridiniales, a large order of thecate species, whereas the unarmored Gymnodiniales appeared more recently, along with members of the Prorocentrales characterized by two thecal plates. In addition, the emergence of heterotrophic species preceded that of photosynthetic species. These results provide new perspectives on proposed evolutionary trees for the dinoflagellates based on morphology, biology, and fossil records. PMID- 1901371 TI - [Prevalence of the HCV associated markers among blood donors in Japan]. PMID- 1901370 TI - Evolution of RNA polymerases and branching patterns of the three major groups of Archaebacteria. AB - The amino acid sequences of the largest subunits of the RNA polymerases I, II, and III from eukaryotes were compared with those of archaebacterial and eubacterial homologs, and their evolutionary relationships were analyzed in detail by a recently developed tree-making method, the likelihood method of protein phylogeny, as well as by the neighbor-joining method and the parsimony method, together with bootstrap analyses. It was shown that the best tree topologies predicted by the first two methods are identical, whereas the last one predicts a distinct tree. The maximum likelihood tree revealed that, after the separation from archaebacteria, the three eukaryotic RNA polymerases diverged from an ancestral precursor in the eukaryotic lineage. This result is contrasted with the published result showing multiple origins for the three eukaryotic polymerases. It was shown that eukaryotic RNA polymerase I evolved much more rapidly than RNA polymerases II and III: The N-terminal half of RNA polymerase I shows an extraordinarily high evolutionary rate, possibly due to relaxed functional constraints. In contrast the evolutionary rate of archaebacterial RNA polymerase is remarkably limited. In addition, including the second largest subunit of the RNA polymerase, a detailed analysis for the branching pattern of the three major groups of archaebacteria was carried out by the maximum likelihood method. It was shown that the three major groups of archaebacteria are likely to form a single cluster; that is, archaebacteria are likely to be monophyletic as originally proposed by Woese and his colleagues. PMID- 1901372 TI - Chemotherapy with high dose ifosfamide/mesna plus cisplatin for the treatment of ovarian cancer: a study of the Grupo de Estudio y Tratamiento Latino-Americano del Cancer. AB - Twenty-one evaluable patients with FIGO stages II-IV epithelial ovarian cancer, median age 57 (range 47-75 years), were treated with ifosfamide (IF), 3 g/m2 diluted in 500 ml saline solution, 8 hour intravenous (i.v.) infusion on days 1 5; mesna 20% of IF dose, i.v. bolus injection, was given at hours 0 and 4; mesna 40% of IF dose by oral route at hours 8 and 12, days 1-5; plus cisplatin 20 mg/m2 diluted in 500 ml saline solution, 2 hour i.v. infusion, days 1-5. Cycles were repeated every 4 weeks. All patients had metastatic lesions (mesentery, pleura, colon, cervix, abdominal wall, lung, liver, bladder, and nodes). Toxicity ranged from mild to moderate. All patients experienced alopecia, nausea, and vomiting. Neutropenia and anemia ranged from mild to moderate. One patient experienced mild brain confusion and two patients microscopic hematuria. Ten clinically complete responses (47%) and five clinically partial responses (23%) were registered, for an overall 70% objective response. However, after a second look performance in 10 patients with clinically complete response, six of 10 patients showed a pathological complete response and four showed pathological partial response. The median duration of complete response is about 33 months, and median partial response duration is 14 months. Although the numbers are small, these data indicate that combination chemotherapy with high dose ifosfamide/mesna plus cisplatin may be an active treatment for advanced ovarian carcinoma. PMID- 1901373 TI - Effects of intravenous methyl palmoxirate on the turnover and oxidation of fatty acids in conscious dogs. AB - Methyl palmoxirate (MP) is a member of a class of hypoglycemic agents that inhibit fatty acid oxidation in vitro. The studies presented here were undertaken to determine the effects of intravenous (IV) MP on tracer-determined rates of fatty acid oxidation and systemic adipose tissue lipolysis in dogs. MP (40 mg/kg) was administered IV to five mongrel dogs using a primed continuous infusion of [1 14C]palmitate to determine palmitate kinetics. Palmitate concentration and rate of appearance decreased rapidly (from 155 +/- 25 to 47 +/- 6 mumol/L and 2.9 +/- 0.5 to 0.9 +/- 0.2 mumol.kg-1.min-1, respectively, at 15 minutes, both P less than .05). Palmitate oxidation also decreased, from 1.5 +/- 0.4 to 0.3 +/- 0.1 mumol.kg-1.min-1, P less than .05. Oxidative clearance decreased by approximately 50% 90 minutes after MP administration (P less than .05). Fractional oxidation of palmitate also decreased by approximately 40% (P less than .05). Plasma insulin increased from 45 +/- 6 to 240 +/- 93 pmol/L at 15 minutes (P less than .05). Plasma glucose decreased over the course of study by approximately 20% (P less than .05). In summary, MP has a specific inhibitory effect on plasma free fatty acid (FFA) oxidation in dogs, confirming previous in vitro observations in an in vivo model. In addition, it has a potent antilipolytic effect when administered IV, an effect likely mediated by stimulation of insulin secretion. The observation that systemic FFA oxidation was only partially suppressed at this relatively high dose of MP is consistent with previous studies suggesting that MP may exert its major effect in the liver, and may be less potent in extrahepatic tissues. PMID- 1901374 TI - Subcellular distribution of adenylyl cyclase and Gs alpha in rat brown adipose tissue. AB - The subcellular distribution of Gs alpha (the alpha-subunit of guanine nucleotide binding stimulatory protein of adenylyl cyclase) was examined in interscapular brown adipose tissue (IBAT) to determine (1) if Gs alpha is completely colocalized with adenylyl cyclase in the plasma membrane, and (2) whether cold exposure, which increases adenylyl cyclase activity, changes the subcellular distribution of Gs alpha. Subcellular fractions were prepared from IBAT by differential centrifugation and analyzed for Gs alpha by immunoblotting. Adenylyl cyclase activity and Gs alpha were detected in all the subcellular fractions except the cytosol. The plasma membrane fraction showed the greatest enrichment of adenylyl cyclase and Gs alpha. However, the enrichment of adenylyl cyclase in the plasma membrane fraction was greater than that for Gs alpha, which was also associated to a large degree with the mitochondrial fraction. Thus, compared with the mitochondrial fraction, both 5' nucleotidase and adenylyl cyclase were enriched by over 200% in the plasma membrane fraction, but Gs alpha was enriched by only 50%. Exposure of rats to 4 degrees C for 3 days increased fluoride stimulated adenylyl cyclase activity, but did not increase the amount of immunoreactive Gs alpha in any of the subcellular fractions examined. The above results demonstrate that not all Gs alpha in IBAT is colocalized with adenylyl cyclase in the plasma membrane. The finding that cold exposure did not change the subcellular distribution of Gs alpha indicates that the cold-induced increase in adenylyl cyclase activity is not due to translocation of Gs alpha from subcellular compartments to the plasma membrane. PMID- 1901376 TI - Perceptions about sexual behavior: findings from a National Sex Knowledge Survey- United States, 1989. AB - Perceptions of specific risk behaviors for sexually transmitted diseases (STDs) can influence socially accepted norms of sexual behavior and knowledge of STD risk among different demographic groups. This report summarizes findings from a national survey (conducted by The Kinsey Institute for Research in Sex, Gender, and Reproduction at Indiana University) that addressed perceptions regarding the prevalence of high-risk sexual behaviors. PMID- 1901375 TI - Elevated intraoperative blood carboxyhemoglobin levels in surgical patients- Georgia, Illinois, and North Carolina. AB - In October 1990, three hospitals, one each in Georgia, Illinois, and North Carolina, reported 26 episodes of elevated blood carboxyhemoglobin (COHb) levels (normal: less than 3% in a nonsmoker, less than 10% in a smoker) during surgery in patients with no known carbon monoxide (CO) exposure. All three hospitals are large, medical-school-affiliated, training institutions. Hospital A (Georgia) reported 15 episodes from January 1987 through September 1989; hospital B (North Carolina), eight episodes from January through October 1990; and hospital C (Illinois), three episodes from January through September 1990. All of the episodes were detected during routine blood gas analyses that included COHb measurements (co-oximetry). In eight episodes, peak COHb levels were greater than 20%. Usually, when an elevated COHb level was detected intraoperatively, 100% oxygen was administered, an alternate gas source was instituted, and COHb levels returned to normal. No deaths or serious complications were reported. PMID- 1901377 TI - Importation of cholera from Peru. PMID- 1901378 TI - Mutated interleukin-5 monomers are biologically inactive. AB - Interleukin-5 contains only two cysteine residues both of which appear to be involved in the dimerisation of the molecule to form a disulphide-linked homodimer (Minamitake et al., J. Biochem. 107, 292-297, 1990). However, it remains unclear whether this linkage is necessary for the bioactivity of this cytokine. Site-directed mutagenesis was used to produce amino acid substitutions of either or both of the cysteines. The mutant proteins were all biologically inactive monomers, however when the two single mutant constructs were co transfected, biologically active IL5 was produced. This is consistent with the dimer forming in a head-to-tail configuration. PMID- 1901379 TI - Structural and functional variability of jacalin. PMID- 1901380 TI - Comparison of heparin and aspirin as adjunctive therapy with tissue plasminogen activator for acute myocardial infarction. PMID- 1901381 TI - A B cell-deficient mouse by targeted disruption of the membrane exon of the immunoglobulin mu chain gene. AB - Of the various classes of antibodies that B lymphocytes can produce, class M (IgM) is the first to be expressed on the membrane of the developing cells. Pre-B cells, the precursors of B-lymphocytes, produce the heavy chain of IgM (mu chain), but not light chains. Recent data suggest that pre-B cells express mu chains on the membrane together with the 'surrogate' light chains lambda 5 and V pre B (refs 2-7). This complex could control pre-B-cell differentiation, in particular the rearrangement of the light-chain genes. We have now assessed the importance of the membrane form of the mu chain in B-cell development by generating mice lacking this chain. We disrupted one of the membrane exons of the gene encoding the mu-chain constant region by gene targeting in mouse embryonic stem cells. From these cells we derived mice heterozygous or homozygous for the mutation. B-cell development in the heterozygous mice seemed to be normal, but in homozygous animals B cells were absent, their development already being arrested at the stage of pre-B-cell maturation. PMID- 1901382 TI - The financial impact of the high technology newborn. PMID- 1901383 TI - In vivo and in vitro effect of Cantastim, an immunomodulatory agent extracted from a highly pathogenic Pseudomonas aeruginosa strain. AB - Cantastim is a biological product consisting of distinct molecules of phospholipids obtained from a peculiar Pseudomonas aeruginosa strain. It enhanced the IgM and especially the IgG responses of mice pretreated with Cantastim and then intraperitoneally inoculated with T-dependent antigens such as sheep erythrocytes; restored cellular immunocompetence as evidenced by an increase in the in vitro proliferative responses to T-cell mitogens and allogeneic stimuli of murine splenocytes from in vivo pretreated mice activated NK cytotoxicity, and inhibited in vivo growth of the Ehrlich ascites tumor. In vitro it stimulated the mitogenesis of mouse lymphocytes but did not exert such stimulatory effect on guinea pig or human lymphocytes. All these findings allow to define Cantastim as an immunomodulating agent influencing mainly the cell-mediated immune response. PMID- 1901384 TI - Fluorescent double labeling of normal and malignant hematopoietic cells by monoclonal antibodies (FITC) and anthracycline cytostatic drug (Daunomycin): a cytometric technique for analysis of drug uptake in hematopoietic cell subpopulations. AB - A technique of simultaneous double labeling of normal and neoplastic hematopoietic cells with FITC-conjugated monoclonal antibodies directed to selectively expressed hematopoietic cell surface antigens (green fluorescence) and the anthracycline cytostatic drug (Daunomycin, red fluorescence) was described. Flow cytometric analysis of double labeled cells permitted anthracycline cell content determination in peripheral blood lymphocytes, granulocytes, monocytes from healthy donors, T- (MOLT-4), non-T, non-B (REH) and myelomonocytic (U-937) leukemic cell lines. After mixing peripheral blood lymphocytes from healthy individuals with cultured leukemic cells labeled on a restrictively expressed hematopoietic cell differentiation antigen (CALLA-CD10-, MHC class II-DR-antigen, a myelomonocytic differentiation antigen) detected by corresponding monoclonal antibodies (DGH-10-1-A9,Bra30, BraC8), the described technique allowed separate measurements of anthracycline content in leukemic cells vs. peripheral blood lymphocytes from healthy donors. Potential diagnostic aspects and research utilization of this technique are discussed. PMID- 1901386 TI - Special neuroendocrine systems. Proceedings of a symposium. Hong Kong, December 1989. PMID- 1901385 TI - The effect of partial hepatectomy on the genotoxicity of aflatoxin B1. AB - The influence of partial hepatectomy on the genotoxic effect of aflatoxin B1 (AFB1) mycotoxin in male Chinese hamsters (Cricetulus griseus) was studied after application of a single i.p. dose of 1.0 mg AFB1/kg. Changes in the fractions of proliferating bone marrow cells, values of the mitotic index of liver cells and morphologic changes in liver tissue were also monitored. Partial hepatectomy reduced significantly the mutagenic activity of AFB1 measured by the frequency of chromosome aberrations in bone marrow cells during 5 days. In hepatectomized animals AFB1 cytotoxicity was significantly reduced as evaluated by changes in the values of proliferating bone marrow cell fractions. There were no important morphologic changes in the liver. In hepatectomized AFB1 treated animals mitotic activity in liver tissue was substantially lower than in hepatectomized but AFB1 untreated animals. PMID- 1901387 TI - Sensory receptors as a special class of hormonal cells. AB - Classically, sensory receptors are specialized cells which detect specific environmental disturbances and send out neural signals for the integration, control and/or regulation of effector organs. Recently, a special class of sensory receptors called sensori-hormonal cells which employ hormones as their means of flux of biological information has been proposed. These sensori-hormonal cells are capable of detecting and transducing environmental signals directly into the secretion of hormones within the same cells. Theoretically, all sensory receptors may have examples capable of direct sensori-hormonal transduction. However, only one group of sensori-hormonal cells, the photoendocrine cells, have so far been studied. The photoendocrine cells including the photoreceptors of fish retinas and pinealocytes of bird pineals are capable of detecting light and/or darkness and transducing the electromagnetic radiation energy into a hormonal output. Generally, light suppresses and darkness stimulates the biosynthesis and secretion of melatonin by these photoendocrine cells. Contrary to many hormonal systems which employ principally the feedback mechanism for regulation, the sensori-hormonal cells are predominantly controlled by the feedforward mechanism. However, other factors may serve as additional means of regulation by influencing the system and affecting the transduction processes and/or the synthesis and secretion of the hormone. The ability of sensori hormonal transduction is suggested to be important for the survival of the organism itself and/or its species and sensori-hormonal cells or their equivalent should appear early in the course of animal evolution. It is further suggested that the sequence of appearance of melatonin functions in the course of evolution would be: hormone--humoral factor--neuromodulator--neurotransmitter. PMID- 1901388 TI - An electrophysiological study on the membrane receptor-mediated action of glucocorticoids in mammalian neurons. AB - The action of glucocorticoids (GC) on neuronal cell membrane was studied in isolated and superfused guinea pig coeliac ganglia by the intracellular recording technique. Cortisol succinate (F) hyperpolarized the membrane potential of 47 of 179 cells and changed the cell's input resistance with a latency of less than 2 min in vitro. The effect persisted under low Ca2+/high Mg2+ superfusing condition and could be blocked by RU 38486, a competitive antagonist of GC cytosolic receptor. Cortisol-21-bovine albumin conjugant exhibited the same effect. Corticosterone (B) elicited hyperpolarization in another 15 of 83 cells, but dexamethasone (Dex) did not. Dex, however, depolarized 2 of 18 cells. Aldosterone, cholesterol and vehicle (ethyl alcohol) caused no detectable change in membrane potential. In vivo studies by iontophoretic application of steroids to hypothalamic paraventricular (PVN) neurons showed that F inhibited the unit discharges in 68 of 97 PVN neurons, and the effect could be antagonized by RU 38486. Dex excited 30 of 100 neurons. Estradiol (E) also inhibited the discharges, but this inhibition was not antagonized by RU 38486. The effect of GC on PVN neurons was also examined in hypothalamic slices including the paraventricular nucleus. B inhibited 28 of 104 units and excited 7 of 104 cells, and both effects could be antagonized by RU 38486. The threshold of inhibitory response was about 10(-7) M, which is close to the physiological level of the hormone in plasma. The results suggest that GC can act non-genomically and specifically through its membrane receptor on the neuronal surface, and that there might be a chemical similarity between the membrane receptor and the traditional cytosolic GC receptor.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1901390 TI - Growth hormone-releasing hormone: clinical studies and therapeutic aspects. AB - Growth hormone-releasing hormone (GHRH) stimulates GH secretion in man and the hormonal response is specific. The attenuation of GH response to bolus GHRH after prior exposure of GHRH of up to 24 h was not demonstrated in normal or GH deficient subjects after more prolonged exposure. This suggests that the partial loss of responsiveness to GHRH may reflect short-term negative feedback by GH. The stimulatory effect of clonidine and L-dopa on GH release is mediated via GHRH. Other stimuli like hypoglycaemia, arginine and propranolol augment GH release in man by modulating hypothalamic somatostatin secretion. Although GHRH test can differentiate between hypothalamic or pituitary cause of GH deficiency, it is of little diagnostic value in children with short stature. Favourable results have been observed in 60-70% of GH-deficient children treated with GHRH, but the dose and mode of administration are still being explored. We found that low dose (1-2 micrograms/kg) GHRH given subcutaneously every 3 h by a pump was effective in promoting growth in 5 of 7 patients after 1 year. Treatment was continued for 2-4 years in 4 patients and growth velocities ranging from 4.5 to 8.2 cm/year were maintained using a dose of 3 micrograms/kg/pulse. PMID- 1901389 TI - A study on the circadian rhythm of glucocorticoid receptor. AB - Circadian rhythm in glucocorticoid receptor (GR) was studied in the rat liver and human peripheral leukocytes. For rats exposed to a natural environmental photic cycle or a 12L:12D artificial light regime, peak values of hepatic GR were detected between 23:00 and 02:00 h. Except for a 4-hour advancement of the peak, a similar circadian rhythm of hepatic GR was detected in rats reared under a reversed lighting regimen (12D:12L; lights on between 18:30 and 06:30 h). In human leukocytes, the peak value of GR was found to parallel that of plasma cortisol with high and low values detected at 04:00-08:00 h and 23:00-24:00 h, respectively. In patients suffering from Cushing's syndrome, the circadian rhythm of plasma cortisol either disappeared or was inverted while that of GR did not significantly deviate from the normal subjects. For apoplexic patients with lesions localized to the base of the brain as indicated by computerized tomography, the diurnal variation of GR was abolished. Conversely, diurnal rhythmicity persisted in apoplexy patients whose lesions were in the cerebral cortex. Thus, we postulated that the circadian modification of GR was independent of the diurnal fluctuations in plasma cortisol level or the circadian variations in environmental lighting and that the rhythmicity might be regulated by the 'circadian pacemaker' located in the human basal brain. These diurnal variations in GR might serve to coordinate the reactivity of the target cells to cortisol because the diurnal rhythms of a GR-mediated response, the fractional inhibition of chemotactic migration rate of polymorphonuclear leukocytes by cortisol, were found to be synchronous with those of GR. PMID- 1901391 TI - Vasoactive intestinal peptide in the hypothalamus and pituitary. AB - Data are presented to show that vasoactive intestinal peptide (VIP) is synthesized and secreted by the hypothalamus and anterior pituitary and that it participates in the regulation of pituitary functions. Immunoreactive VIP in the hypothalamus and pituitary is increased following estrogen treatment and adrenalectomy and is reduced in hyperprolactinemic states. The level of VIP mRNA in the hypothalamus is increased during lactation and sexual maturation, while that in the anterior pituitary shows a sexual dimorphism and is increased with estrogen treatment and hypothyroidism. All these findings suggest a physiological regulation of hypothalamic and pituitary VIP gene expression in relation to its potential role as a neuroendocrine hormone. Furthermore, VIP stimulates prolactin (PRL) release at concentrations attainable in the hypophyseal-portal blood. Passive immunoneutralization studies with anti-VIP antisera suggest that endogenous VIP acts at multiple loci in the hypothalamic-pituitary axis to regulate PRL secretion, interacting possibly with other regulators of PRL secretion such as estrogen, serotonin, cholecystokinin, prostaglandins, galanin and oxytocin. Regarding other pituitary functions, although VIP has been shown to release growth hormone, ACTH, and vasopressin in vivo and in vitro, the physiological significance of these findings remains to be determined. PMID- 1901392 TI - Rhythmic release pattern of pineal melatonin in rodents. AB - The plasma melatonin in the confluens sinuum of anesthetized rabbits and rats exhibited an episodic release pattern, with pulses superimposed on a basal level. The rhythmicity of pineal melatonin release revealed by our experimental paradigm was dependent on the blood sampling interval. In rabbits, it was found that the plasma melatonin level in the confluens sinuum was 7-15 times higher than that obtained from the plasma collected at the same time from the peripheral artery where the melatonin level also showed a pulsatile pattern. Diurnal variation in pineal melatonin level in the confluens sinuum was observed only in acutely blinded rabbits and rats. Electrical stimulation of the unilateral cervical sympathetic trunk of rabbits resulted in elevation of the level of plasma melatonin in the confluens sinuum, while the frequency of pulse peaks of plasma melatonin revealed at 4-min intervals was not affected. Similar results were obtained in rabbits with systemic administration of beta-adrenergic agents. These findings suggest that the release of pineal melatonin into the confluens sinuum is under the regulation of the cervical sympathetic system. The sympathetic influence on pineal melatonin secretion seems to vary with age. Furthermore, age related fluctuation of systemic blood melatonin appeared to be the results of changes in the rate of pineal melatonin secretion, body growth and ageing. PMID- 1901393 TI - Endocrine control of hypothalamic and pituitary met-enkephalin and beta-endorphin contents. AB - This review summarizes the recent findings on the effects of endocrine manipulation on the hypothalamic and pituitary contents of met-enkephalin and beta-endorphin. In the pituitary, gonadectomy decreases beta-endorphin content in both the anterior lobe and neuro-intermediate lobe. Orchidectomy results in a decrease while ovariectomy leads to an increase in anterior lobe met-enkephalin contents. Adrenalectomy only lead to an increase in beta-endorphin contents in the anterior pituitary lobe. Hypothyroidism induced by propylthiouracil treatment is accompanied by a decrease of beta-endorphin in the neuro-intermediate lobe and a decrease in met-enkephalin in the anterior lobe while thyroidectomy entails a decrease in met-enkephalin in the anterior lobe only. Chemically induced diabetes mellitus results in a decrease in beta-endorphin content in the hypothalamus and the neuro-intermediate lobe, and a reduction in met-enkephalin level in the anterior and neuro-intermediate lobes. All these changes are reversible with appropriate hormone treatments. These results indicate the importance of hormones in the regulation of the synthesis and/or release of the opioid peptides in the hypothalamus and the pituitary. PMID- 1901394 TI - Differential effect of recombinant tissue plasminogen activator-induced thrombolysis in the central nervous system and systemic arteries. AB - Recombinant tissue plasminogen activator (rTPA) has been more effective in inducing thrombolysis in laboratory studies of intracranial thrombosis than clinical studies of systemic or coronary thrombosis would indicate. To evaluate this discrepancy, 21 rabbits were subjected to embolic occlusion of the right internal carotid artery (ICA) by retrograde injection of a tin-tagged, 2-hour-old autologous clot through the external carotid artery with angiographic monitoring in the same manner as in a previously reported model. The emboli lodged intracranially at the bifurcation of the ICA in 10 animals and in the cervical ICA in 11 animals. Digital subtraction angiography confirmed total occlusion of the ICA in all animals. Treatment started one-half hour after embolization and consisted of a bolus of 0.5 mg/kg of rTPA followed by an infusion of 1 mg/kg/h for 2 hours. All of the animals with intracranial emboli and 6 of the animals with cervical emboli were treated intravenously. The remaining 5 animals with cervical emboli were treated by intracarotid infusion of the same dose of rTPA. In the intravenously treated group, serial digital subtraction angiography documented thrombolysis in 9 of the 10 animals with intracranial emboli and only 1 of the 6 with cervical emboli. Thrombolysis occurred in 4 of the 5 rabbits with cervical emboli treated with intracarotid rTPA. Intravenous rTPA therapy produced a significantly (P less than 0.01) higher rate of thrombolysis in intracranial as compared to cervical thrombus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1901395 TI - Brain biopsy in tuberculoma: the risks and benefits. AB - In developing countries, 5 to 8% of the space-occupying lesions of the central nervous system are tuberculomas. Diagnosis can be difficult in the absence of extracranial tuberculosis; computed tomography is suggestive only. To assess the value of brain biopsies in tuberculomas, the records of 15 patients aged 6 to 80 years were reviewed. Histological confirmation was obtained in 15 patients, and acid-fast bacilli were cultured from 12 patients. Intracranial hypertension was the principal sign in 11 patients; other neurological signs were related to the location of the tuberculoma. One patient had evidence of extracranial tuberculosis. Biopsy-related complications consisted of an epidural hematoma in 1 patient and hydrocephalus in another; both required additional surgery. One case of tuberculous meningitis was probably related to surgery and poor drug compliance. There was no postoperative mortality. Thirteen patients (2 were lost to follow-up) were cured after an average of 16 months of antituberculous therapy. It was concluded that the brain biopsy is useful in diagnosing tuberculoma but that there is some associated risk. PMID- 1901396 TI - Increased free light chains in the urine from patients with multiple sclerosis. AB - We quantitated free kappa (kappa) and lambda light (L) chains in coded urine specimens from subjects with clinically definite multiple sclerosis (MS) (N = 56), other neurologic diseases (OND) (N = 30), and age-matched normal controls (N = 28). Urine from MS patients showed statistically significant increases in free L chains compared with the other groups, although there was overlap between MS patients and OND patients. The ratio of kappa/creatinine was significantly greater in the relapsing-remitting MS group than in patients with clinically stable MS, OND, and normal controls. Elevated free L chains were usually independent of urinary albumin and beta 2-microglobulin levels. Serial studies showed that urinary free kappa/creatinine ratios were elevated during periods of clinical worsening in seven of eight MS patients and subsequently decreased during clinical recovery. The measurement of free L chains in urine obtained at intervals from MS patients may be useful as a marker to monitor disease activity. PMID- 1901398 TI - Dopaminergic photosensitivity. PMID- 1901397 TI - Vigabatrin in drug-resistant partial epilepsy: a 5-year follow-up study. AB - We treated 75 patients with drug-resistant complex partial seizures and secondarily generalized seizures with vigabatrin as additional therapy for 6 months. Twenty-one patients either showed no benefit from vigabatrin treatment or had side effects. The remaining 54 patients entered into the long-term study. The median monthly seizure frequency decreased from 12.5 at baseline to 3.3 at the 3 month visit, and was 3.9 after 5 years of therapy in 28 patients who continued using the drug after the 5-year period. During 5 years of therapy with vigabatrin, 26 patients have withdrawn from the study because of various reasons: loss of efficacy (14), suspected side effects (5), noncompliance (3), administrative reasons (2), pregnancy (1), and epilepsy surgery (1). In all, 19 patients had a greater than 50% seizure frequency reduction at 5 years, representing 35% of the 54 patients who entered the long-term study, or 25% of the 75 patients who were initially recruited into the efficacy study. PMID- 1901399 TI - The ethics of informed consent in relation to prevention screening programmes. PMID- 1901400 TI - A systems approach to the management of nursing services--Part II: Patient classification system. PMID- 1901401 TI - Ets1, when fused to the GAL4 DNA binding domain, efficiently enhances galactose promotor dependent gene expression in yeast. AB - Ets1, the translation product of the c-ets1 proto-oncogene and the related Ets2 protein, act as sequence-specific transcriptional factors in transient transfection experiments in animal cells. We report here that in S. cerevisiae, expression of a lacZ test gene placed under the control of the GAL1 promoter is stimulated efficiently by a fusion protein in which the chicken Ets1 sequence starting from amino acid 37, is linked to the DNA binding domain of the yeast GAL4 transcriptional activator. This suggests that Ets1 contains one or more intrinsic transcription activation domain(s). However, the GAL4 integral of Ets1 fusion protein was unable to restore growth of a gal4 deletion mutant on galactose, implying that the fusion product cannot substitute for GAL4 enhancement on all GAL genes. PMID- 1901403 TI - [RU 51807 (cefpodoxime proxetil). In vitro and in vivo antibacterial activity of a new orally administered active cephalosporin]. AB - Cefpodoxime proxetil (RU 51807) is an enterally absorbed ester prodrug which is rapidly cleaved in vivo after oral administration, with release of the active free acid metabolite cefpodoxime. The in vitro antibacterial activity of the sodium salt of cefpodoxime (RU 51746) against approximately 800 clinical isolates was evaluated comparatively with other orally active beta-lactams. RU 51746 was found to be active against enterobacteria normally susceptible to third generation cephalosporins, with MIC50 values ranging from 0.02 mg/l (Providencia sp) to 5 mg/l (C. freundii). RU 51746 was also active against H. influenzae, including beta-lactamase producing strains (MIC50 0.04 mg/l), oxa-S S. aureus (2,5), beta-hemolytic streptococci (0.05) and S. pneumoniae (0.002). Oxa-R staphylococci and P. aeruginosa were resistant to RU 51746 (MIC50 greater than 40 mg/l for both organisms). The antibacterial activity of RU 51746 was bactericidal in nature and independent from test conditions. The molecule was stable to all the beta-lactamases studied, with the exception of cefuroximase (type Ic). RU 51746 exhibited no strong inhibitory effects on these enzymes, except with Enterobacter P99 (type Ia). A good correlation was found between in vivo activity of RU 51807 and in vitro activity of RU 51746. Cefpodoxime proxetil was found to be more effective than cefaclor in mice with experimental septicemia caused by various streptococci, with a DP50 ratio in the 10-100 range. This advantage was again evidenced for septicemias due to various enterobacteria. In contrast, cefaclor proved more effective in experimental staphylococcus infections. In mice with experimental pneumonia, cefpodoxime proxetil caused sharp falls in K. pneumoniae lung counts. Six days after induction of the infection, 60% of animals under cefpodoxime proxetil had sterile lungs, versus 25% of animals under amoxicillin. PMID- 1901402 TI - Transcriptional and post-transcriptional regulation of c-fos expression by the tumor promoter okadaic acid. AB - Phosphorylation events are major regulatory mechanisms of signal transduction pathways that control cell growth and differentiation. We analyzed the potential contribution of serine/threonine specific protein phosphatases to the regulation of the c-fos gene, a proto-oncogene that is involved in the regulation of cell growth and differentiation. By use of okadaic acid, an inhibitor of protein phosphatases 1 and 2A, we present evidence that expression of the c-fos gene is regulated by serine/threonine specific protein phosphatases. This control is exerted on the transcriptional as well as the post-transcriptional level. The results suggest that dephosphorylation of regulatory phosphoproteins is an important mechanism for the down-regulation of c-fos promoter activity and the rapid degradation of c-fos mRNA. Examination of two protein kinase pathways that are known to regulate c-fos expression indicated that okadaic acid acted synergistically with protein kinase C, but not with protein kinase A. Since inhibition of serine/threonine specific phosphatases increases proto-oncogene expression, these experiments further strengthen the view that certain protein phosphatases may act as negative regulators of cell growth. PMID- 1901404 TI - Receptor-mediated deactivation of Gk in cardiac myocytes. AB - The muscarinic potassium current IK(ACh) of atrial myocytes can be evoked in the absence of agonists by intracellular application of stable GTP analogs (GXP). This receptor-independent opening of K(ACh) channels is a consequence of the direct activation of the guanyl nucleotide binding protein Gk that couples muscarinic receptors to K(ACh) channels, and was previously thought to be unaffected by subsequent application of agonist. We report here that in the presence of GTP, application of a pulse of muscarinic agonist to atrial cells can abolish the GXP-induced IK(ACh). The results imply that in intact cells the agonist-bound receptor can interact with Gk not only in its inactive, GDP-bound form, but also in its active, GXP-bound form in a process that promotes the release of guanine nucleotide from its binding site. PMID- 1901405 TI - Isolation of two cDNAs encoding zinc finger proteins which bind to the alpha 1 antitrypsin promoter and to the major histocompatibility complex class I enhancer. AB - Two partial cDNAs coding for DNA-binding proteins (AT-BP1 and AT-BP2) have been isolated. Both proteins, when prepared from lambda gt11 lysogens, bind to the B domain of the alpha 1-antitrypsin promoter, an element which is important for the liver-specific expression of alpha 1-antitrypsin. Analysis of the cDNA sequences encoding these proteins reveals that both contain two zinc fingers of the Cys2 His2 type followed by a highly acidic stretch of 20 amino acids. AT-BP1 contains a second putative DNA-binding domain consisting of an 8-fold repeat of a SPKK (Ser-Pro-Lys/Arg-Lys/Arg) motif. Both proteins bind to the NF-kappa B recognition site in the MHC gene enhancer with significantly higher affinity than to the kappa immunoglobulin gene enhancer, or to the B-domain of the alpha 1-antitrypsin gene promoter. Analysis of mRNA expression shows that AT-BP1 and AT-BP2 are expressed in all the tissues examined. While the physiological roles of AT-BP1 and AT-BP2 remain to be elucidated, their predicted amino acid sequence and their DNA-binding characteristics suggest a role as transcriptional regulators. PMID- 1901407 TI - Differential response of the human 6-16 and 9-27 genes to alpha and gamma interferons. AB - 9-27 mRNA is expressed to a high level in response to both alpha and gamma interferons. In contrast, 6-16 mRNA is expressed well in response to alpha but very poorly in response to gamma interferon in human cells. The factors governing these different levels of expression were investigated. For both genes the major effect of both interferons is on transcription. A transcriptional bias in the 6 16 promoter/enhancer accounts in large part for the differential response of 6-16 to the two interferons. No single DNA element appears responsible; the smaller the 5' region analysed the lower the absolute activity and the smaller the differential response to alpha and gamma interferons observed. Both the 6-16 and 9-27 mRNAs are very stable and no effect of the interferons on stability was detected. Nor was any direct evidence obtained for preferential processing of the 9-27 mRNA. Nevertheless, differentials between the transcription and accumulation of mature mRNAs, particularly for 6-16 mRNA in response to gamma interferon, suggest that post-transcriptional control(s) must additionally operate. The 9-27 5' promoter/enhancer is much less active than that from 6-16 when placed 5' of a marker gene, despite the similar response of the two genes to alpha interferon. PMID- 1901406 TI - Physical and biochemical characterization of recombination-dependent synthesis of linear plasmid multimers in Bacillus subtilis. AB - The synthesis and structure of linear multimeric plasmid molecules (hmw DNA) in Bacillus subtilis were investigated. The replication of covalently-closed circular supercoiled (form I) DNA requires the rate-limiting plasmid-encoded replication initiation protein. Unlike form I, hmw DNA synthesis is partially resistant to inhibition of cellular transcription or translation and requires the host DnaB protein. In addition, hmw DNA synthesis involves host recombination and repair functions (RecE and Poll). Analysis of hmw DNA by electron microscopy displayed linear DNA molecules up to 100 kb in size, which were either single stranded, double-stranded or double-stranded with single-stranded ends. Structural features of hmw DNA molecules were mapped by means of heteroduplex studies using defined strand-specific probes. The results suggest that a recombination intermediate, but not plasmid-encoded replication, is involved in the initiation of hmw DNA synthesis. PMID- 1901408 TI - Dinucleotide repeat polymorphism at the human interleukin 9 gene. PMID- 1901409 TI - Open learning. Conversion--counting the cost. PMID- 1901410 TI - Administering total parenteral nutrition. PMID- 1901411 TI - Adhesion versus coreceptor function of CD4 and CD8: role of the cytoplasmic tail in coreceptor activity. AB - CD4 and CD8 play an important role in T-cell recognition and activation; however, their mechanisms of action are not well understood. We compare the effects of expressing CD4 and CD8 alpha either individually or together in a class II restricted T-cell hybridoma. We also compare the effects of expressing truncated forms of CD4 or CD8 alpha that do not have a cytoplasmic tail and thus do not associate with the T-cell-specific tyrosine kinase p56lck, which has been implicated in T-cell activation. We demonstrate that, although CD4 and CD8 alpha can specifically enhance interleukin 2 secretion, maximal potentiation occurs with expression of CD4, which, unlike CD8, can bind to the same major histocompatibility complex protein as the T-cell receptor. Our data further indicate that the cytoplasmic tail and/or the associated p56lck are primarily significant for interleukin 2 secretion by the hybridomas we have examined when CD4 or CD8 can bind to the same major histocompatibility complex ligand as the T cell receptor. PMID- 1901413 TI - Functional interdependence of the yeast SNF2, SNF5, and SNF6 proteins in transcriptional activation. AB - The SNF2, SNF5, and SNF6 genes of Saccharomyces cerevisiae are required for expression of a variety of differently regulated genes. Previous evidence implicated the SNF5 protein in transcriptional activation, and a DNA-bound LexA SNF5 fusion protein was shown to activate expression of a nearby promoter. Here, we examine the functional relationship of the SNF2, SNF5, and SNF6 proteins. Activation by DNA-bound LexA-SNF5 fusion protein was greatly reduced in snf2 and snf6 mutants, indicating that activation by LexA-SNF5 requires SNF2 and SNF6 function. An spt6 mutation, which suppresses transcriptional defects caused by snf2, restored activation by LexA-SNF5 in a snf2 mutant. The SNF2 gene was sequenced and encodes a 194-kDa protein that is targeted to the nucleus. DNA bound LexA-SNF2 fusion protein also activated transcription, dependent on SNF5 and SNF6. These findings suggest that SNF2, SNF5, and SNF6 function interdependently in transcriptional activation, possibly forming a heteromeric complex. PMID- 1901412 TI - Phosphorylation of a Ras-related GTP-binding protein, Rap-1b, by a neuronal Ca2+/calmodulin-dependent protein kinase, CaM kinase Gr. AB - A neuron-specific Ca2+/calmodulin-dependent protein kinase, CaM kinase Gr, phosphorylates selectively a Ras-related GTP-binding protein (Rap-1b) that is enriched in brain tissue. The phosphorylation reaction achieves a stoichiometry of about 1 and involves a serine residue near the carboxyl terminus of the substrate. Both CaM kinase Gr and cAMP-dependent protein kinase, but not CaM kinase II, phosphorylate identical or contiguous serine residues in Rap-1b. The rate of phosphorylation of Rap-1b by CaM kinase Gr is enhanced following autophosphorylation of the protein kinase. Other low molecular weight GTP-binding proteins belonging to the Ras superfamily, including Rab-3A, Rap-2b, and c-Ha-ras p21, are not phosphorylated by CaM kinase Gr. The phosphorylation of Rap-1b itself can be reversed by an endogenous brain phosphoprotein phosphatase. These observations provide a potential connection between a neuronal Ca2(+)-signaling pathway and a specific low molecular weight GTP-binding protein that may regulate neuronal transmembrane signaling, vesicle transport, or neurotransmitter release. PMID- 1901414 TI - Localization of carbonic anhydrase IV in a specific capillary bed of the human eye. AB - Carbonic anhydrase (CA) activity plays an important role in controlling aqueous humor production in the eye and in regulating intraocular pressure. Prior studies identified the soluble isozymes CA II and CA I in the human eye and also suggested a distinct membrane-associated CA. We used an antibody to CA IV, the membrane-anchored isozyme from human lung, to study CA IV in eye tissues and to compare its distribution with that of CA II. We found intense immunostaining for CA IV associated with endothelial cells of one specific uveal capillary bed, the choriocapillaris. CA IV was not detected in endothelial cells of the contiguous capillaries of the iris or in endothelial cells of other vessels. Immunoreactivity for CA IV was also intense in epithelial and fiber cells of the lens but was not detectable in the neuroretina, the ciliary process (except for capillaries), and the cornea, all sites where immunostaining with anti-CA II antibody was intense. These studies indicate that the membrane-associated CA in human eye, which was suspected from histochemical studies, is CA IV. Defining the physiological role of this ocular isozyme remains a challenge. PMID- 1901415 TI - Interleukin 1 alpha inhibits prostaglandin E2 release to suppress pulsatile release of luteinizing hormone but not follicle-stimulating hormone. AB - Interleukin 1 alpha (IL-1 alpha), a powerful endogenous pyrogen released from monocytes and macrophages by bacterial endotoxin, stimulates corticotropin, prolactin, and somatotropin release and inhibits thyrotropin release by hypothalamic action. We injected recombinant human IL-1 alpha into the third cerebral ventricle, to study its effect on the pulsatile release of follicle stimulating hormone (FSH) and luteinizing hormone (LH) in conscious, freely moving, ovariectomized rats. Intraventricular injection of 0.25 pmol of IL-1 alpha caused an almost immediate reduction of plasma LH concentration; this decrease was statistically significant 20 min after injection and occurred through a highly significant reduction in the number of LH pulses, with no effect on pulse amplitude. In contrast, there was no change in pulse frequency but a small significant elevation in amplitude of FSH pulses. Intraventricular injection of the diluent had no effect on gonadotropin release. The results provide further evidence for separate hypothalamic control mechanisms for FSH and LH release. To determine the mechanism of the suppression of LH release, mediobasal hypothalamic fragments were incubated in vitro with IL-1 alpha (10 pM) and the release of LH-releasing hormone (LHRH) and prostaglandin E2 into the medium was measured by RIA in the presence or absence of norepinephrine (50 microM). IL-1 alpha reduced basal LHRH release and blocked LHRH release induced by norepinephrine. It had no effect on the basal release of prostaglandin E2; however, it completely inhibited the release of PGE2 evoked by norepinephrine. To evaluate the possibility that IL-1 alpha might also interfere with the epoxygenase pathway of arachidonic acid metabolism, epoxyeicosatrienoic acids were also measured. IL-1 alpha had no effect on the content of epoxyeicosatrienoic acids in the hypothalamic fragments as measured by gas chromatography and mass spectrometry. In conclusion, IL-1 alpha suppresses LH but not FSH release by an almost complete cessation of pulsatile release of LH in the castrated rat. The mechanism of this effect appears to be by inhibition of prostaglandin E2-mediated release of LHRH. PMID- 1901418 TI - Randomized double-blind study of fluvoxamine and maprotiline in treatment of depression. AB - In a six-week double-blind randomized trial, preceded by a one-week period of single-blind placebo treatment, the efficacy and the side-effects of fluvoxamine (100-300 mg/d) (n = 24) and maprotiline (50-150 mg/d) (n = 24) were compared in moderately depressed outpatients with DSM-III Major Depression (n = 22) or Dysthymic Disorder (n = 26). Efficacy was measured by means of the Hamilton Depression Rating Scale, the Zung Depression Selfrating Scale, and a Clinical Global Impression of Severity Scale. Side-effects were evaluated by an Adverse Event Inventory and a Psychosomatic Symptom Scale. A statistically significant improvement was achieved in both treatment groups but success rates were modest: in both groups, 29% of the patients achieved a clinically significant improvement after six weeks of treatment. After six weeks of treatment, no difference in efficacy was found between fluvoxamine and maprotiline. Nausea was the most common complaint in the fluvoxamine group, while in the maprotiline group, it was dry mouth and constipation. One maprotiline-treated patient developed a convulsive attack. PMID- 1901416 TI - Analysis of affinity and structural selectivity in the binding of proteins to glycosaminoglycans: development of a sensitive electrophoretic approach. AB - Members of several families of cell surface and secreted proteins bind glycosaminoglycans (GAGs), the structurally heterogeneous polysaccharides found on proteoglycans. To understand the physiological significance of the interactions of proteins with GAGs, it is critical that relationships between GAG structure and binding be analyzed. It is particularly important that interactions depending on common structural features of GAGs (e.g., size, charge density, and disaccharide repeat unit) be distinguished from those mediated by specific sequences of carbohydrate modification. Gathering the information needed to make such distinctions has so far been difficult, however, partly because structurally homogeneous samples of GAGs are lacking but also because of technical difficulties associated with performing and interpreting assays of protein-GAG binding. We describe an electrophoretic method useful for both measuring affinity and evaluating structural selectivity in protein-GAG binding. Data are presented on the binding of the GAG heparin to the protease inhibitor antithrombin III, the acidic and basic fibroblast growth factors, and the extracellular matrix protein fibronectin. Results obtained with fibronectin are consistent with a model in which high-affinity binding (Kd approximately 34 nM) is mediated through the recognition of specific carbohydrate sequences. PMID- 1901417 TI - Apolipoprotein A-I deficiency due to a codon 84 nonsense mutation of the apolipoprotein A-I gene. AB - The molecular genetic defect of a female patient with apolipoprotein A-I (apoA-I) deficiency and premature atherosclerosis was examined. Her parents were first cousins. Her plasma density fraction from 1.063 to 1.21 g/ml contained no apoA-I on SDS/PAGE and no measurable high density lipoprotein cholesterol. Southern blot hybridization showed no gross abnormality to be present in the patient's apoA-I gene and homozygosity for a haplotype of restriction fragment length polymorphisms in the apoA-I gene region. Sequencing after amplification by PCR revealed a codon 84 nonsense mutation (CAG----TAG, Gln----stop) of exon 4 and a codon 67 missense mutation (GCC----ACC, Ala----Thr) of exon 3 in the patient's apoA-I gene. The data from dot-blot hybridization with allele-specific oligonucleotide probes indicated that she was homozygous for the apoA-I gene with regard to the two mutations. The codon 37 missense mutation was also detected in the apoA-I gene of 6 out of 60 controls, who all had normal levels of apoA-I and high density lipoprotein cholesterol, suggesting that the missense mutation is polymorphic and not associated with apoA-I deficiency. These findings indicate that homozygosity for the apoA-I gene with codon 84 nonsense mutation causes the deficiency of apoA-I and of high density lipoprotein cholesterol in the patient. PMID- 1901419 TI - Chest muscle activity and panic anxiety: a preliminary investigation. AB - This report represents a pilot investigation of the role of chest muscle electromyographic (EMG) activity in developing panic episodes. Chest EMG activity was obtained as part of a larger study examining ventilatory differences between panic sufferers and normal controls. Frontalis EMG, heart rate, and minute ventilation (breathing rate and tidal volume) were also obtained during the study. The ventilatory procedure involved exposing the subjects to three periods of carbon dioxide gas inhalations (1%, 3%, 5%; balance oxygen). Subjective measures of frightening cognitions and body sensations were obtained across the inhalation phases as well. The panic disorder subjects were divided, on the basis of subjective anxiety ratings obtained throughout the study, into high anxious (HA) and low anxious (LA) panic disorder groups. The HA panic disorder patients exhibited significantly higher chest EMG activity than the LA panic disorder patients and controls across all phases of the experiment. In addition, the chest EMG predicted, better than the other physiologic measures, the number of frightening cognitions and sensations reported by the subjects during the baseline and 5% CO2 inhalation phases. Overall, the results were supportive of the further study of chest wall EMG activity in the pathogenesis of panic attacks. PMID- 1901421 TI - Major histocompatibility complex: a system for the specific modulation of differentiated cells? PMID- 1901420 TI - Endogenous activation of prostaglandin synthesis in rabbit colonic explants cultured in vitro. AB - Rabbit colonic biopsy specimens cultured in vitro showed an optimal release of prostaglandin E2 (PGE2) after 6-7 h of incubation. The amplitude but not the PGE2 production profile was dependent on stimuli applied--that is, A23187 greater than phorbol 12-myristate 13-acetate greater than control. This study was undertaken to determine the nature of this time-dependent optimum. The following hypotheses were tested: increased substrate availability, de novo synthesis of prostaglandin synthetase (PS), and translocation of PS or increased activity of PS. Arachidonic acid, either continuously present or given as a pulse, increased the overall amplitude equally but did not change the production profile. Cycloheximide, 0.2 microM, which inhibited 50% of the protein synthesis, increased the PGE2 production by 80% at 7 h. The cytoskeletal disrupting agent cytochalasin B had no effect. Homogenates of specimens cultured 6 h showed an increased PGE2 production. This was partly explained by a large increase in the PGE2 production capacity of the particulate matter obtained after 45 min of centrifugation at 100,000 g. It is concluded that the PGE2 production peak is due to an activation of preformed PS and that the PS activity is under the control of a peptide inhibitor, dependent on protein synthesis. PMID- 1901422 TI - Mechanism of T-cell activation by mycobacterial antigens in inflammatory synovitis. AB - Earlier studies demonstrated enhanced proliferative responses to an acetone precipitable Mycobacterium tuberculosis (AP-MT) antigenic complex by T lymphocytes from the synovial fluid, compared with the peripheral blood, of patients with inflammatory synovitis, including rheumatoid arthritis. In contrast, decreased proliferation and interleukin 2 (IL-2) production in response to mitogens by synovial fluid lymphocytes from patients with rheumatoid arthritis has been demonstrated. In order to determine if IL-2 was produced in response to AP-MT, the peripheral blood and synovial fluid of patients with inflammatory arthritis were analysed by measuring proliferation and IL-2 production in response to AP-MT and tetanus toxoid. A reduction of IL-2 production relative to proliferation was observed in some, but not all, synovial fluids of patients who responded to the AP-MT. Nevertheless, antibodies to IL-2 as well as interleukin 4 (IL-4), significantly inhibited proliferation of synovial fluid lymphocytes by AP MT. There was no inhibition by antibodies to interleukin 6 (IL-6). We conclude that AP-MT induced proliferation by synovial fluid lymphocytes is mediated by both IL-2 and IL-4. PMID- 1901423 TI - Intraoperative autotransfusion in reconstructive hip joint surgery of patients with rheumatoid arthritis and ankylosing spondylitis. AB - The efficacy of a simple, low-cost device designed for intraoperative blood salvage and reinfusion, known as the Sorensen system, was studied during 24 hip joint operations in adult patients suffering from rheumatoid arthritis or ankylosing spondylitis. The total need for homologous blood was reduced to 28%, compared with a matched control group of patients who had previously undergone hip surgery by homologous blood replacement. In primary hip-replacement operations, the need for blood was met either completely by autotransfused blood or by the addition of 1 or 2 units of homologous blood. In revision arthroplasties, the maximal need for homologous blood was 6 units owing to a greater blood loss during operation. Postoperative changes in several hematologic variables measured were all very small. The autotransfusion system proved easy and safe to operate. No patients manifested complications. In our experience, the system may be considered an underutilized resource in rheumatological surgery. PMID- 1901425 TI - Antiviral AIDS drug nears approval. PMID- 1901424 TI - A genetic tool used to identify thioredoxin as a mediator of a growth inhibitory signal. AB - Loss of sensitivity to growth inhibitory polypeptides is likely to be one of the events that participates in the formation of some tumors and might be caused by inactivation or loss of the genetic elements that transduce these extracellular signals. The isolation of such a gene was achieved by randomly inactivating genes by an anti-sense complementary DNA expression library followed by direct selection for growth in the presence of an inhibitory polypeptide. Thus, a gene whose inactivation conveyed growth resistance to interferon-gamma (IFN-gamma) was isolated. Sequence analysis showed complete identity with human thioredoxin, a dithiol reducing agent, implicated here in the IFN-gamma-mediated growth arrest of HeLa cells. PMID- 1901426 TI - Late recurrence of spinal stenosis and claudication after laminectomy due to an ossified extradural pseudocyst. PMID- 1901427 TI - Gene for murine alpha 1----3-galactosyltransferase is located in the centromeric region of chromosome 2. AB - The gene for alpha 1----3-galactosyltransferase, termed Ggta-1, was mapped to mouse chromosome 2 by Southern blot analysis of Chinese hamster x mouse somatic cell hybrids. Using an intersubspecies back-cross, this locus was positioned to the centromeric region on this chromosome, near the Hc locus. PMID- 1901428 TI - Katayama fever in scuba divers. A report of 3 cases. AB - Katayama fever or acute schistosomiasis probably occurs more commonly than is recorded. Interviews with a 3-man scuba diving team who had had contact with a large dam in an endemic area of the eastern Transvaal Lowveld at the same time and contact area on the same day during late summer of 1986 are discussed. Two, who had not previously been exposed to infected water, presented with Katayama fever, due to Schistosoma mansoni infection, 21 days after contact and it took 30 36 months for them to recover fully after several treatments. The third patient, a keen water-sportsman and resident in the endemic area for a period of 10 years, presented with a mild infection, probably due to acquired immunity initiated during previous contacts with infected water; he took about a year to recover. The pathogenesis, clinical features, diagnosis and treatment of the 3 cases are described in the light of recent observations made elsewhere on Katayama fever cases and the effects of chemotherapy on the course of illness. The necessity of obtaining basic information on the travel and water-contact activities of patients in order to make a diagnosis is emphasised. PMID- 1901429 TI - Trends in medical care costs--rapid increases continue. AB - Extensive efforts to restrain the rise in health care costs have not had a pronounced impact. The health care system in the United States has undergone significant changes, and as we entered the 1990s, a shift toward managed care was gathering momentum. Nevertheless, spending on medical care continues to rise by nearly 10 percent a year, thus increasing the percentage of GNP these costs represent. With substantial progress in lowering the rise of health care costs unlikely in the near future, the debate over some form of national program is bound to intensify. PMID- 1901430 TI - [Lung lesions of drug origin accompanied by hypereosinophilia]. AB - A study is presented of 16 patients with eosinophilic lesions of the lungs due to drug treatment. The disease was characterized by a reduction of T-lymphocytes, inhibition of the enzymatic activity of leucocytes, dysproteinemia with hypergammaglobulinemia and reduction of IgG concentration. Patients with a high eosinophilia in the blood revealed a severe course of the disease with polysystemic involvement. The therapeutic effect was achieved only by means of prednisolone monotherapy. At the remote period they developed as a rule bronchial asthma. Patients with moderate eosinophilia showed a more favourable course, treatment proved successful with employment of nonsteroid anti-inflammatory agents, antihistaminic drugs in combination with nondrug treatment. PMID- 1901431 TI - [The correction of the hemodynamic disorders in acute pancreatitis patients by intravenous nitroglycerin infusions]. PMID- 1901432 TI - Effects of exogenous monoiodotyrosine on the serum levels of anterior pituitary hormones. AB - Monoiodotyrosine is a tyrosine hydroxylase inhibitor. Ingestion of one gram monoiodotyrosine caused a 10,000-fold increase of serum monoiodotyrosine from basal levels of 0.69 +/- 0.20 nmol/l to a peak of 10.6 +/- 1.7 mumol/l in women and 7.1 +/- 2.3 mumol/l in men 30 min later, and the t1/2 was 45 min. Monoiodotyrosine stimulated PRL to a peak of 170 +/- 51 micrograms/l in women and 90 +/- 6 micrograms/l in men 30 min after the monoiodotyrosine peak, or 60 min after the ingestion. Other anterior pituitary hormones were unchanged. Dopamine infusion or L-dopa pretreatment attenuated the monoiodotyrosine effect. TRH exaggerated the PRL peak, and chlorpromazine did not increase but prolonged the hyperprolactinemia. These results suggest that dopamine synthesis inhibition may be the mechanism of PRL stimulation. PMID- 1901434 TI - Uterine binding sites for LH/hCG can be modulated by hormonal status in rabbits and rats. AB - High-affinity LH/hCG binding sites have been identified in both porcine and rabbit uteri. We have now identified these binding sites in rat uteri. We have assessed the binding site specificity and modulation and have searched for binding sites for a related glycoprotein. Radioreceptor assays were performed with membrane homogenates of uterine tissue, and were analysed for binding site specificity, affinity, and capacity. The rabbit and rat LH/hCG binding sites did not bind human TSH or human FSH. Rabbit uterine tissue contained no binding sites for FSH, as determined with 125I-labelled FSH and unlabelled FSH. Pretreatment of rabbits with hCG decreased their uterine binding site capacity from 1.30 +/- 0.29 to 0.46 +/- 0.01 fmol/mg protein. Pretreatment of castrated rabbits with estrogen or estrogen combined with progesterone did not alter the binding site affinity or capacity. In rats, the uterine binding site number was shown to vary inversely with the serum LH concentration and directly with the ovarian LH/hCG binding site number during the estrus cycle. Hypophysectomy resulted in a significant increase in uterine binding site capacity in rats. Estrogen treatment prevented this hypophysectomy-induced increase. The function of these LH/hCG binding sites remains uncertain; however, the lack of binding sites for a related glycoprotein and the modulation of these binding sites by hormonal factors strengthen the concept that uterine tissue might respond in a specific manner to direct LH/hCG stimulation. PMID- 1901433 TI - Age-related alterations in prolactin binding sites in the female rat. AB - Aging is associated with various neuroendocrine alterations, including in the rat a hypersecretion of PRL with maintained ovulations (repetitive pseudo-pregnancy) and a reduced activity of the hypothalamic dopaminergic neurons with loss of the neuron responsiveness to PRL, suggestive of age-related alterations in PRL receptors. In this study we have investigated PRL binding sites in the hypothalamus as well as in the mammary glands, the ovaries and the liver of young and old nulliparous female rats. The old rats (26-28 months) displayed spontaneous repetitive pseudopregnancies and they were compared with young (4-6 months) pseudopregnant rats; the binding studies were performed by saturation analysis using 125I-oPRL as ligand and particulate membrane preparations. In the hypothalamus, a negligible binding of PRL was observed in all fragments studied, mediobasal hypothalamus, median eminence, in both young and old rats and no characterization of the binding sites could be achieved. In the mammary glands, the number of PRL binding sites was appreciable in spite of the nulliparity of the rats, but it was smaller in the old than in the young rats (9.0 +/- 1.4 vs 14.9 +/- 1.2 fmol/mg protein; mean +/- SEM; p less than 0.02). In the ovaries, the density of PRL binding sites was similar in the old and young rats (112.6 +/- 9.7 vs 115.0 +/- 8.9 fmol/mg protein), illustrative of a maintained luteotropic effect of PRL with age in the rat. In contrast, in the liver a greater number of binding sites was found in the old than in the young rats (261.9 +/- 36.6 vs 63.6 +/- 5.8 fmol/mg protein; p less than 0.001), supportive of the ability of PRL to induce its own receptors in that tissue. The affinity constant of PRL binding was not altered with age in the tissues studied. These results are illustrative of tissue-specific modifications in the number of PRL binding sites with age and they are suggestive of a sustained biological activity of PRL in the old rats. PMID- 1901435 TI - [Grand mal like attack by interferon injection in case of renal cell carcinoma]. AB - We performed a radical nephrectomy for renal cell carcinoma on a 60-year-old female. We began to give alpha-interferon (natural type), she had an attack of tonic clonic convulsion (like grand mal attack). There were no abnormal findings in head computed tomography, nor hematologic tests. We ascribed the attack to interferon, and stopped giving it. Because there was an abnormal wave in EEG, she was given an anti-convulsant per os. One month later, the electroencephalogram became normal and she showed no neurological symptoms nor findings. PMID- 1901436 TI - An economic evaluation of lovastatin for cholesterol lowering and coronary artery disease reduction. AB - The costs and benefits of cholesterol lowering in the primary prevention of coronary artery disease (CAD) were considered using lifetime lovastatin therapy as the intervention model for adults between 35 and 55 years of age. The analysis projected the benefits of CAD risk reduction using estimates from the Framingham Heart Study. The chosen analytic perspective was that of the patient. For average risk men with total serum cholesterol levels between 5.69 and 9.83 mmol/liter (220 and 380 mg/dl), the cost per life-year saved ranged from $9,000 to $106,000, whereas for average-risk women, the cost ranged from $35,000 to $297,000 (1989 U.S. dollars). In high-risk men (with smoking habit and hypertension), the cost per life-year saved values ranged from 6,000 to $53,000, whereas in high-risk women the cost per life-year saved values ranged from $19,000 to $160,000. The results were more favorable than those found in previous studies of alternate medication therapies for hypercholesterolemia. Even using conservative parameter assumptions, at least 800,000 Americans aged 35 to 55 years are at sufficiently high risk for CAD, so that the net cost of lovastatin therapy can be favorably compared with other widely used medical interventions. PMID- 1901437 TI - Effects of time required for reperfusion (thrombolysis or angioplasty, or both) and location of acute myocardial infarction on left ventricular functional reserve capacity several months later. AB - The purpose of this study was to determine whether reperfusion of acute myocardial infarction (AMI) by recombinant tissue-type plasminogen activator (rt PA) or percutaneous transluminal coronary angioplasty, or both, would improve left ventricular (LV) function when it is measured several months later at rest or maximal bicycle exercise, or both. Radionuclide angiography was performed in 44 patients 5 months (range 6 weeks to 9 months) after AMI to assess function, and tomographic myocardial thallium-201 imaging was performed at maximal exercise and delayed rest to determine whether there was any evidence of myocardial ischemia. As expected, no patient had chest pain or redistribution of a thallium defect during the exercise test, because patients had undergone angioplasty (n = 28) or coronary bypass graft surgery (n = 5) where clinically indicated for revascularization. The LV ejection fraction was plotted as a function of the time elapsed between the onset of chest pain and the time when coronary angiography confirmed patency of the infarct-related artery (achieved in 91% of 44 patients by rt-PA [n = 31] or percutaneous transluminal coronary angioplasty [n = 9] ). Functional responses differed markedly between patients with anterior (n = 20) versus inferior (n = 24) wall AMI. LV ejection fraction during exercise correlated with time to reperfusion in patients with an anterior wall AMI (r = 0.58; standard error of the estimate = 11.9%; p less than 0.02) but not in patients with an inferior AMI (r = 0.10; standard error of the estimate = 13.1%; difference not significant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1901438 TI - Incremental prognostic value of exercise hemodynamic variables in chronic congestive heart failure secondary to coronary artery disease or to dilated cardiomyopathy. AB - To determine the prognostic value of hemodynamic variables at rest and during exercise, 49 patients with chronic congestive heart failure undergoing hemodynamic evaluation at rest and during symptom-limited exercise were followed for 1 year. One-year mortality rate was 33%. On univariate analysis, nonsurvivors differed significantly from survivors in pulmonary arterial wedge pressure at rest (22 +/- 10 vs 15 +/- 10 mm Hg; p = 0.01) and during exercise (32 +/- 9 vs 24 +/- 9 mm Hg; p = 0.003), stroke work index at rest (19 +/- 6 vs 25 +/- 9 g-m/m2; p = 0.03) and during exercise (20 +/- 7 vs 32 +/- 14 g-m/m2; p = 0.001) and exercise-induced increment in stroke work index (0.5 +/- 0.4 vs 7 +/- 8 g-m/m2; p = 0.004), but not with respect to left ventricular ejection fraction, exercise duration, peak oxygen consumption or peak left ventricular hydraulic power. Patients with a peak exercise stroke work index less than 20 g-m/m2 had a 66% mortality rate compared with a mortality rate of 13% in patients with a peak exercise stroke work index greater than 20 g-m/m2 (p = 0.0001). Multiple logistic regression analysis identified pulmonary arterial wedge pressure at rest and peak exercise stroke work index as the only independent predictors of mortality. A receiver-operating characteristic curve analysis revealed that peak exercise stroke work index provided significant incremental prognostic information over the resting hemodynamic variables.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1901439 TI - Spontaneous or experimentally induced formation of a special zone in the adrenal cortex of the adult brush-tailed possum (Trichosurus vulpecula). AB - The cytology and ultrastructure of the hypertrophied special zone, which is formed spontaneously in the adrenal cortex of adult female brush-tailed possums (Trichosurus vulpecula), was compared to the adrenocortical tissue in adult males in which the special zone, normally absent, was induced following castration alone or by additional treatment with follicle-stimulating hormone (FSH). The special zone in females was situated between the zona fasciculata and the zona reticularis, the latter being a rudimentary zone in this species. Special zone tissue extended as a broad band parallel to and on one side of the adrenal medulla. In the luteal phase of the reproductive cycle, the special zone cells showed ultrastructural features commonly associated with steroidogenic tissues, with many mitochondria and compact masses of smooth endoplasmic reticulum. Cytoplasmic lipid inclusions were rarely observed. In lactating females, however, the special zone cells exhibited cytological and ultrastructural features suggestive of a transformation in their morphology broadly divided into two types of cells: (1) cells at the periphery of the special zone (closest to the zona fasciculata) showed variable quantities of lipid inclusions, mitochondria with dispersed cristae, and segregation of the smooth endoplasmic reticulum into compact masses; (2) cells within the more central regions showed an increasing abundance of lipid inclusions which in many cells became the dominant feature of the cytoplasm. These special zone cells contained very little smooth endoplasmic reticulum and their mitochondria contained few cristae together with amorphous granular material within the matrix. In castrated males, special zone tissue developed between the zona fasciculata and the zona reticularis, appearing initially as focal islands of cells (8 months postcastration) and later (11 months postcastration) expanding into a single zone, probably via the proliferation and differentiation of adjacent cells of the zona fasciculata and longitudinal growth of the special zone. Similar focal aggregations of special zone cells were induced after 14 days of FSH treatment given to 2-month castrated males. In all castrated and FSH-treated castrated males, the ultrastructure of special zone cells was similar to that of special zone cells in luteal-phase female possums. The findings suggest that the formation and cellular composition of the special zone is associated with changes in the pituitary-gonadal axis and that FSH plays a primary role in the differentiation of this tissue. PMID- 1901440 TI - Influence of dietary fat on plasma lipid profiles of Malaysian adolescents. AB - We studied the effects of saturated (palm olein) and polyunsaturated (soybean oil) cooking oils on the lipid profiles of Malaysian male adolescents eating normal Malaysian diets for 5 wk. Diets cooked with palm olein did not significantly alter plasma total-cholesterol, LDL cholesterol, and HDL cholesterol concentrations or the ratio of total cholesterol to HDL cholesterol compared with diets cooked with soybean oil. However, the diet cooked with palm olein significantly increased apolipoprotein A-I (11%) and apolipoprotein B (9%) concentrations. Unexpectedly, soybean-oil-cooked diets caused a significant increase (47%) in plasma triglycerides compared with palm-olein-cooked diets. We conclude that palm olein, when used as cooking oil, has no detrimental effects on plasma lipid profiles in Malaysian adolescents. PMID- 1901441 TI - Effects of palm carotenoids in rat hepatic cytochrome P450-mediated benzo(a)pyrene metabolism. AB - Using benzo(a)pyrene (BaP) metabolism as a probe for chemical carcinogenesis, in vitro and in vivo effects of palm-oil carotenoid [beta-carotene (BC), alpha carotene (AC), or canthaxanthin (CTX)] on BaP metabolism in the rat hepatic cytochrome P450-mediated monooxygenase system were studied. Apparent Michaelis Menten constants (Km) for formation of the precursor carcinogen, 7,8-dihydrodiol BaP, were found to be 14.4 (BC), 1.74 (AC), and 0.7 (CTX) mumol/L. The order of anticarcinogenic strength established in this study was BC much greater than AC greater than CTX. Increased formation of the detoxification intermediate, 3 hydroxy BaP, with increased carotenoid concentration was observed. The order of detoxification strength was BC greater than AC = CTX. The presence of carotenoids in vivo inhibited BaP metabolism. Using 9,10-dihydrodiol BaP as an indicator for inhibition, the order of the antioxidative activity was palm oil (with carotenoids) greater than BC greater than CTX greater than palm oil (without carotenoids). BC and AC may selectively modify the rat-liver microsomal enzymes, thus providing a biochemical mechanism for the inhibitory effect of palm carotenoids on chemical carcinogenesis. PMID- 1901442 TI - Post-sclerotherapy bacterial peritonitis. AB - Endoscopic variceal sclerotherapy has been associated with a number of complications. Peritonitis after sclerotherapy has rarely been reported. In this retrospective review of 213 consecutive sclerotherapy procedures among 65 patients over a 3-yr period, we found that six cases of peritonitis occurred, for an incidence of approximately 3%. All patients developing post-sclerotherapy peritonitis had low ascitic fluid protein. However, this did not differ from patients who did not develop peritonitis. No patient on antibiotics at the time of sclerotherapy developed peritonitis. Peritonitis should be considered in the diagnosis of post-sclerotherapy fever. The role of prophylactic antibiotics to prevent this complication is uncertain. PMID- 1901443 TI - Incidental microvesicular steatosis due to valproic acid anticonvulsant therapy. AB - Valproic acid has been implicated in at least 100 cases of fatal acute liver failure. Most cases have occurred in patients less than 10 yr old; however, at least seven have involved adults. Microvesicular steatosis has been uniformly observed, but its incidence in less severe liver disease and in asymptomatic patients receiving valproate is unknown. We report two patients receiving maintenance valproate, one with resolving acute hepatitis C and the other with chronic persistent hepatitis C, with incidental microvesicular steatosis demonstrated on oil-red O stains. We conclude that microvesicular steatosis does not necessarily signify hepatotoxicity in patients on chronic valproic acid, and should not lead to discontinuation of the drug until other causes of acute or chronic liver disease have been excluded. PMID- 1901444 TI - Platelet satellitosis to polymorphonuclears: cytochemical, immunological, and ultrastructural characterization of eight cases. AB - Satellitosis of platelets to polymorphonuclears was observed in eight patients. This phenomenon occurred only in blood anticoagulated by EDTA at room temperature. In vivo and in vitro platelet and neutrophil function were normal. Electron microscopy studies showed normal structures in both cells but demonstrated platelet phagocytosis by neutrophils. In all cases we were able to transfer the platelet satellitosis factor by mixing platelet plasma (or serum) with whole blood from ABO compatible healthy controls; conversely, when the same plasma (or serum) was pre-incubated with anti-IgG serum, satellitosis to normal blood was not observed. While this finding suggests that a plasmatic protein with the properties of an IgG immunoglobulin was probably responsible for the phenomenon, we were unable to correlate it with the clinical condition of the patient, functional abnormalities of the blood components, or drugs. PMID- 1901445 TI - Therapy of the Kasabach-Merritt syndrome with cryoprecipitate plus intra-arterial thrombin and aminocaproic acid. AB - A patient with the Kasabach-Merritt syndrome with disseminated intravascular coagulopathy and congestive heart failure due to a giant hepatic cavernous hemangioma achieved thrombosis of his tumor with a combination of cryoprecipitate plus intra-arterial thrombin and epsilon aminocaproic acid. This was documented by an absence of Indium 111-labelled platelet sequestration, marked decrease in thrombin:antithrombin complex generation, and normalization of platelet count and fibrinogen. Interventional angiography with aminocaproic acid and thrombin is advocated in patients whose tumors are amenable to such an approach so as to avoid a systemic antifibrinolytic state. PMID- 1901446 TI - Cost-effectiveness of prospective and continuous parenteral antibiotic control: experience at the Palo Alto Veterans Affairs Medical Center from 1987 to 1989. AB - PURPOSE: Controlling inappropriate antibiotic usage is a major focus for hospital quality assurance and cost-containment programs. We assessed the impact of strengthening a parenteral antibiotic control policy and instituting continuous infectious disease service (IDS) reviews of the appropriateness of antimicrobial therapy on cost and patient outcomes. PATIENTS AND METHODS: All patients receiving intravenous antibiotics during a 3.5-year period from 1986 to 1989 were included in either the pre- or post-policy study group. Antibiotic costs 16 months before were compared with antibiotic costs 26 months after implementation of a new policy to restrict inappropriate usage of (1) broad-spectrum antibiotics when not necessary, (2) expensive agents when a less costly agent could be used, and (3) an excessive dosage or interval. Patient subgroups treated 4 months before and 4 months after policy implementation were compared further within diagnosis-related group (DRG) assignments using patient demographic, cost, and outcome measures. RESULTS: The average monthly antibiotic costs during the 26 month post-policy period were $7,600 less than during the 16-month pre-policy period (p less than 0.0001), resulting in an average yearly drug cost reduction of $91,200. The IDS team altered therapy in 611 (34.5%) of 1,769 reviews of antibiotic usage during the 26-month period. The comparisons among similar patient groups by DRG classification revealed the average number of antibiotic doses per study patient admission was decreased 24% (p = 0.005) and drug costs were reduced 32% (p = 0.004) after policy implementation. In two DRG categories (i.e., respiratory infections plus pneumonia), patients in the post-policy group had a 33% decrease in average number of doses (p = 0.05) and 45% decrease in antibiotic costs (p = 0.04) compared with the pre-policy group. Similar trends were observed in most DRG categories. There was an average $70 per admission decrease in drug cost and a reduction of eight antibiotic doses per admission after policy initiation. The overall prevalence of deaths (p = 0.22) and average length of antibiotic therapy (p = 0.29) were less in the post-policy period despite group similarities in patient characteristics and lengths of hospital stay. CONCLUSION: Antibiotic control policies can be developed to ensure quality care and can be designed to select for cost-effective agents. Prospective and continuous monitoring of antibiotic usage by the IDS resulted in a significant and sustained reduction in antibiotic costs without detrimental effect on the length of therapy or deaths. PMID- 1901447 TI - Autoantibodies and rheumatic disorders in a neurology inpatient population: a prospective study. AB - PURPOSE: To determine the prevalence and spectrum of underlying rheumatic diseases, especially Sjogren's syndrome (SS) and the antiphospholipid syndrome, and the prevalence of the lupus anticoagulant, antinuclear antibody (ANA), and rheumatoid factor (RF) within a neurologic patient population. PATIENTS AND METHODS: The study design entailed a prospective, consecutive sample of patients admitted to a university-affiliated neurology service for 72 hours or more. Study patients were obtained from a sequential evaluation of 100 inpatients with a wide spectrum of neurologic diseases. Another 31 eligible patients were not included due to refusal (n = 4), inability to give consent (n = 12), or an incomplete database (n = 15). All patients underwent a physical examination and responded to a rheumatic disease questionnaire (administered by one rheumatologist) assessing signs and symptoms relevant to rheumatic disease. All had lupus anticoagulant, ANA, and RF determinations. An independent patient evaluation was done by the attending neurologist. RESULTS: Eleven patients had a rheumatic or autoimmune disorder directly related to their neurologic admission: three patients with SS (one each with embolic stroke, dementia, and hemiparetic somatization); three patients with lupus anticoagulant syndrome (all with stroke, recurrent in two); one patient with systemic lupus erythematosus accompanied by migraine headache and the lupus anticoagulant; and one patient each with isolated central nervous system (CNS) angiitis, neuro-Behcet's disease, CNS Whipple's disease, and HLA-B27 associated spondyloarthropathy. Nineteen patients had one or more autoantibodies: ANA greater than or equal to 1:80 (n = 10); RF greater than or equal to 1:80 (n = 6); and positive lupus anticoagulant (n = 7). The seroreactivity of 10 of these patients remained unexplained. CONCLUSIONS: This neurologic population demonstrated significant seroreactivity and rheumatic disease associations, with SS and lupus anticoagulant-related neurologic disease the most common. Since SS and the antiphospholipid syndrome can be overlooked, it is recommended that a formal evaluation for SS and a direct lupus anticoagulant assay should be considered in the examination of patients with neuropsychiatric symptoms. PMID- 1901448 TI - Flexible sigmoidoscopy for colorectal neoplasia. PMID- 1901449 TI - Effect of calcium and calcium antagonists on phospholipid secretion induced by lung inflation in newborn rabbits. AB - The effect of calcium and selected calcium antagonists on the lung phospholipid secretion associated with lung distension was examined in newborn rabbits. Lung distension was produced by saline lavage or air inflation in freshly killed pups. Calcium or calcium antagonists were added to the lavage solution. The fractional stimulation of secretion with 1.0 mM calcium was 1.94 +/- 0.28 (p less than 0.01), but ethylene diamine tetraacetic acid (EDTA) did not have the expected inhibitory effect. There was dose-related inhibition of phospholipid secretion induced by the calcium antagonist, lanthanum, the fractional recovery decreasing from 1.0 +/- 0.23 at 10(-5) molar, to 0.43 +/- 0.19 at 0.5 x 10(-4) molar, to 0.22 +/- 0.03 at 10(-4) molar and 0.19 +/- 0.05 at 10(-3) molar (p less than 0.001). This inhibition was significantly reversed by the addition of 10 mM calcium. Although nifedipine and verapamil had no effect, nickel and cadmium also inhibited secretion. Therefore, it is likely that lanthanum acted as a calcium channel blocker, suggesting the importance of extracellular calcium. The observation that intense calcium chelation with ethylene glycol bis aminoethylether tetraacetic acid-bis-aminophenoxyethane tetraacetic acid (EGTA BAPTA) had a significant inhibitory effect, supports the conclusion that a superficial calcium pool in the plasma membrane may be an important stimulus for phospholipid secretion during lung distension. The inhibitory effect of neomycin, a drug known to displace superficial calcium, was consistent with this conclusion. PMID- 1901450 TI - Misoprostol. PMID- 1901451 TI - Neurofibromatosis I: predicting the relation of gene structure to gene function. PMID- 1901452 TI - Confirmation of linkage between juvenile myoclonic epilepsy locus and the HLA region of chromosome 6. AB - Juvenile myoclonic epilepsy (JME) is a generalized, non-progressive epilepsy characterized by an adolescent onset of sudden, involuntary myoclonic jerks. Greenberg et al. (American Journal of Medical Genetics 31:185-192, 1988b; Cytogenetics and Cell Genetics 51:1008, 1989b) reported tight linkage of a JME locus to the HLA region of chromosome 6p. We confirm this linkage assignment, although at a larger recombination fraction than previously reported. Twenty three, mostly nuclear, families were ascertained through a JME proband. The affected status of relatives of the probands was assigned by 4 different clinical criteria, and separate analyses were done assuming an autosomal dominant model with 90% penetrance and an autosomal recessive model with full penetrance. A linear age-of-onset correction with maximum penetrance at age 20 years was incorporated into the analyses. The maximum lod score obtained was 3.11 at (-)m = 0.001, (-)f = 0.20, assuming autosomal dominant inheritance and using the second definition of the disease phenotype. There was strong support for linkage using the other phenotype definitions and the autosomal dominant model, although the lod scores did not exceed 3.0. There was also support for linkage of a JME locus to this region under the autosomal recessive model, although the results varied depending upon the definition of the disease phenotype. There was no significant evidence for linkage heterogeneity. PMID- 1901453 TI - Variable expression of albinism within a single kindred. AB - We studied the albinotic characteristics in 13 members of a white family (age range, 2 to 73 years), which were graded according to severity and were correlated with visual acuity. Clinical, electrophysiologic, and biochemical characteristics of this family do not fit any known category of human albinism. The degree of heterogeneity in expression of albinotic features was unexpected. The correlation between visual acuity and nystagmus was particularly strong. The brown-haired propositus had severe skin involvement, iris transillumination, fundus hypopigmentation, and foveal hypoplasia. He had no manifest nystagmus, however, and his visual acuity was nearly normal. These observations suggest that nystagmus imposes a visual deficit beyond that related to foveal hypoplasia alone. PMID- 1901454 TI - Inhibition of mineralization of glutaraldehyde-pretreated bovine pericardium by AlCl3. Mechanisms and comparisons with FeCl3, LaCl3, and Ga(NO3)3 in rat subdermal model studies. AB - In the present study, the authors investigated the mechanism by which Al3+ preincubations inhibited the pathologic calcification of glutaraldehyde pretreated bovine pericardium (GPBP) implanted subdermally in rats. The concentration dependency of the Al3+ anticalcification effect was compared with that of other trivalent metal ions (Fe3+, Ga3+, La3+) known to interact with calcium phosphates. In vitro incubations of GPBP were carried out in AlCl3 (10( 3) mol/l [molar] to 10(-1) mol/l) to ascertain both the optimal conditions for uptake of Al3+ and the time course of Al3+ dissociation. Al3+ uptake by GPBP was concentration dependent and occurred rapidly, with tissue levels after 1 hour not differing significantly from those after 72 hours of incubation. Analyses of GPBP samples preincubated in AlCl3 (0.1 mol/l, 24 hours) showed that more than 75% of the Al3+ remained tightly bound after 60 days' in vitro release at 37 degrees C, pH 7.4. Preincubations of GPBP in AlCl3 significantly inhibited calcification after subdermal implantation in rats for 60 days (Ca++ = 5.1 +/- 0.9 microgram/mg, 11.5 +/- 4.6 micrograms/mg, 70.3 +/- 23.0 micrograms/mg, mean +/- standard error [SE], for 10(-1) mol/l, 10(-2) mol/l, 10(-3) mol/l AlCl3, respectively), compared with controls (Ca++ = 110.0 +/- 9.3 micrograms/mg). All animals were free of Al3(+)-mediated adverse effects on bone, as determined by light microscopic evaluation of femoral epiphyseal growth plates. Transmission electron microscopy coupled with electron energy loss spectroscopy (EELS) of GPBP incubated in 10(-1) mol l AlCl3 for 24 hours demonstrated discrete Al3+ localization in the sarcolemma and cytoplasmic and nuclear membranes of devitalized pericardial connective tissue cells at intracellular sites coincident with phosphorus loci. Similar intracellular localization remained prominent in explants removed after 60 days; no calcific deposits were noted in these specimens. Preincubations in Fe3+ but not Ga3+ and La3+ solutions yielded significant inhibition of GPBP calcification, which did not differ significantly from that provided by Al3- and had a comparable concentration dependency. Light microscopic examination (Prussian blue staining) and EELS of FeCl3-preincubated explants demonstrated Fe3+ localization within devitalized GPBP connective tissue cells. The authors conclude that Al3+ and Fe3+ significantly inhibit the pathologic mineralization of glutaraldehyde-pretreated bovine pericardium by mechanisms that are likely related to the high affinity of these cations for membrane associated and other intracellular phosphorus loci. PMID- 1901455 TI - Characterization of target injury of murine acute graft-versus-host disease directed to multiple minor histocompatibility antigens elicited by either CD4+ or CD8+ effector cells. AB - The precise identity of effector mononuclear cells capable of eliciting acute graft-versus-host disease (AGVHD) is controversial. In this study, highly purified subsets of donor T cells were used to produce AGVHD to multiple minor histocompatibility (H) antigens in two strain combinations of mice matched for the major histocompatibility complex (MHC). In the C3H.SW- greater than B6 strain combination, only CD8+ effector cells produced histologic evidence of AGVHD in skin and liver, which peaked 3 weeks after transplant. In the B10.D2- greater than DBA/2 strain combination, CD4+ effector cells, and to a lesser extent, CD8+ cells, mediated disease in skin, liver, and intestine, which peaked during the fourth week after transplant. Analysis of skin and liver from both combinations showed target cell injury that was phenotypically similar and resembled that previously described in human disease in other studies. In addition, prominent epithelial injury also was detected in oropharyngeal mucosa, esophagus, hepatobiliary ducts, and seminal vesicle in both transplant settings. These findings indicate that functionally different subsets of donor T cells may be capable of initiating common pathways of cellular injury in selected target sites in AGVHD, and have potential implications for strategies that seek to ablate disease development by manipulation of donor marrow before transplantation. PMID- 1901456 TI - Intracellular betaine substitutes for sorbitol in protecting renal medullary cells from hypertonicity. AB - Renal medullary cells are normally exposed to a variably high extracellular NaCl concentration. They compensate by accumulating large amounts of organic osmolytes, including sorbitol and betaine. The sorbitol is synthesized from glucose, catalyzed by aldose reductase. Previously, inhibition of aldose reductase activity was noted to greatly reduce renal medullary cell survival and growth (measured by cloning efficiency) in tissue cultures of renal medullary cells in hypertonic medium. In contrast, inhibition of aldose reductase and renal medullary sorbitol accumulation is not associated with kidney damage in vivo. In the present experiments we find that addition of betaine to the medium, and its resultant uptake by the cells, largely replaces the decrease in sorbitol caused by aldose reductase inhibitors and restores the cloning efficiency. We presume that in vivo uptake of betaine by renal medullary cells similarly protects them from harm when aldose reductase inhibitors lower sorbitol. The results also demonstrate that one organic osmolyte can substitute for another in protecting cells from hypertonicity, consistent with the compatible osmolytes hypothesis. PMID- 1901458 TI - Comment on PCO2 in renal cortex. PMID- 1901457 TI - A novel metalloproteinase present in freshly isolated rat glomeruli. AB - We have utilized [3H] gelatin to document high activity of a metalloproteinase present in freshly isolated rat glomeruli. [3H] gelatin degradation by glomeruli was markedly inhibited by EDTA (10 mM: -89 +/- 2.3%) and o-phenanthroline (2 mM: 72 +/- 0.1%), inhibitors of metalloproteinases. No significant inhibition of [3H]gelatin degradation was observed with inhibitors of serine or cysteine proteinases. Most (greater than 80%) of the glomerular metalloproteinase (GLOMP) activity was associated with the pellet after centrifugation of sonicated glomeruli at 100,000 g for 90 min. The pH optimum for gelatin degradation by sonicated glomeruli was approximately pH 8.5. Sodium dodecyl sulfate substrate (gelatin)-polyacrylamide gel electrophoresis revealed a single major band of EDTA inhibitable gelatin-degrading activity with a molecular mass of approximately 116 125 kDa. The GLOMP activity was not inhibited by tissue inhibitors of metalloproteinases, did not appear to be latent, and was not activated by organomercurial activators of several latent metalloproteinases. GLOMP activity was increased 3.4-fold after incubation with trypsin (20 micrograms/ml, 25 min, 22 degrees C). These data indicate that GLOMP is distinct from the previously described matrix metalloproteinases, as well as other metalloproteinases present in the kidney, including the gelatinase secreted by cultured mesangial cells, Meprin, and endopeptidase 24.11 (enkephalinase, EC 3.4.24.11). PMID- 1901460 TI - Effect of dexamethasone on cerebral prostanoid formation and pial arteriolar reactivity to CO2 in newborn pigs. AB - This study investigates the effect of glucocorticoid treatment on the relationship between arteriolar PCO2 and cortical prostanoid production and on cerebrovascular responsiveness to elevated CO2 in newborn piglets. The response of pial arteries to hypercapnia (fractional inspired CO2 = 0.035 and 0.07) was studied in 18 anesthetized newborn piglets, 9 of which were pretreated with dexamethasone (2 mg.kg-1.day-1 for 36-48 h). Pial arterioles (77-122 microns diam) were monitored using a closed cranial window and intravital microscopy. Perivascular cerebrospinal fluid (CSF) was sampled from the cortical surface and analyzed for 6-keto-prostaglandin F1 alpha and thromboxane B2 (TxB2) using radioimmunoassay. In the dexamethasone-treated animals the increase in arteriolar diameter to CO2 was diminished by approximately 50% for each respective CO2 concentration vs. the control group. Acute sympathetic denervation did not restore the CO2 dilator response. Dexamethasone did not alter baseline cortical CSF prostanoid concentrations but abolished the CO2-induced increase in CSF prostanoids. The dilator response to exogenously applied prostaglandin E2 was inhibited in dexamethasone-treated animals. However, the dilator response to exogenous adenosine and the contractile response to prostaglandin F2 alpha were not altered in the dexamethasone-treated piglets. The data support the concept that metabolites of arachidonic acid participate in the cerebrovascular response to CO2 and suggest that glucocorticoid treatment may influence cerebrovascular tone via this mechanism. PMID- 1901459 TI - Increase in sympathetic activity with age. I. Role of impairment of arterial baroreflexes. AB - The purpose of this study was to evaluate changes in arterial baroreflex function with aging. Mean arterial pressure (MAP) obtained in the awake state was 110 +/- 7 mmHg in the young animals (1 yr; n = 5) and 128 +/- 6 mmHg in the old beagles (11 yr; n = 11) (P less than 0.05). In response to bolus administration of varying doses of phenylephrine and nitroglycerin in the conscious state, the slope relating heart rate (HR) to MAP was attenuated significantly in the old animals compared with the young (-0.87 +/- 0.30 vs. -2.35 +/- 0.44 beats.min 1.mmHg-1; P less than 0.05). After atropine, the baroreflex control of HR was abolished in both groups. After anesthesia and sectioning of the aortic depressor nerves, and with isolated carotid sinus pressures (CSP) held at 50 mmHg, absolute renal sympathetic nerve activity (RSNA) was significantly greater in the old (368 +/- 40 Hz) vs. the young animals (41 +/- 9 Hz). In the old, the gains of baroreflex inhibition of MAP (0.78 +/- 0.09) and normalized RSNA (0.38 +/- 0.14%/mmHg) during increases in CSP were decreased significantly compared with the young (MAP, 1.16 +/- 0.17 mmHg, and RSNA, 0.72 +/- 0.06%/mmHg). In a subgroup of old normotensive animals (n = 5), the baroreflex gain of RSNA was still attenuated (0.43 +/- 0.11%/mmHg) compared with the young. The reflex reduction in absolute RSNA as a function of baseline RSNA was also impaired in old vs. young beagles.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1901461 TI - Effect of occluding one umbilical artery on placental oxygen transport. AB - Placental O2 transport was studied in seven fetal lambs before and after occluding one of the two umbilical arteries. Ethanol was used to measure uterine and umbilical blood flows using the steady-state transplacental diffusion method. Blood samples were drawn from umbilical artery, umbilical vein, both uterine veins, and maternal artery and analyzed for blood flow indicator, O2 content, PO2, PCO2, and pH. Occlusion reduced the placental mass and the uterine blood flow, which was available for transplacental exchange, to 49.5 and 46.5% of control, respectively. After occlusion, fetal blood pressure increased 38%, total umbilical blood flow decreased 25%, total fetal O2 uptake decreased 26%, fetal blood flow to the unoccluded placenta increased 52%, and the O2 flux from unoccluded placenta to fetus increased 49%. This increased flux was accompanied by a decrease in the PO2 of maternal venous blood from the unoccluded placenta and an enlargement of the transplacental PO2 gradient, resulting in a marked drop in umbilical venous PO2 (28.3 to 17.7 Torr). This evidence supports the hypothesis that placental O2 diffusing capacity is a limiting factor in placental O2 transport and agrees with other studies indicating the absence of homeostatic mechanisms for preventing acute changes of PO2 in the placental circulation. PMID- 1901462 TI - Suppression of puberty in rats by exercise: effects on hormone levels and reversal with GnRH infusion. AB - In an effort to better understand the effects of prolonged exercise on the hypothalamic-pituitary-ovarian axis, we made a variety of comparisons between young female rats in two treatment groups: 1) prolonged exercise, in which growth and reproductive development were arrested at a peripubertal stage by requiring rats to run for long periods of time in order to obtain food; and 2) voluntary exercise, in which same-aged control rats were fed ad libitum and given free access to a running wheel. The pulsatile secretion of luteinizing hormone (LH) and growth hormone were completely suppressed by the prolonged exercise treatment. Mean levels of follicle-stimulating hormone, prolactin, and thyroid stimulating hormone were not affected. Prolonged exercise elevated corticosterone titers, and the secretory pattern of this steroid was changed out of phase with running activity. Tissue levels of gonadotropin-releasing hormone (GnRH) in the hypothalamus and LH in the pituitary were enhanced, not suppressed, by prolonged exercise. Most importantly, pulsatile infusions of GnRH reinstated normal pubertal development and ovulation in rats still growth restricted by the prolonged exercise treatment. The results of this study indicate that the suppressive effects of prolonged exercise somehow affect the production of the hypothalamic GnRH-pulse generator signal. PMID- 1901463 TI - Caval thrombolysis in neonates using low doses of recombinant human tissue-type plasminogen activator. AB - Four neonates suffered caval thrombosis secondary to indwelling central catheters. Dissolution of thrombus with recombinant tissue plasminogen activator (rt-PA) as a low-dose infusion (0.05 mg/kg/hr) directly into thrombus was successful in three patients. rt-PA was ceased after three days in the fourth patient because of catheter malposition. Thrombolysis was achieved between four and ten days. Rethrombosis occurred in one patient despite heparin prophylaxis. Plasminogen activator infusions were titrated to maintain fibrinogen levels above 100 mg/dl. One neonate suffered an intracranial haemorrhage. Regional rt-PA is an alternative to thrombectomy in critically ill neonates. PMID- 1901464 TI - The effects of 2% alkaline glutaraldehyde solution on the elastic properties of elastomeric chain. AB - The effect of two proprietary alkaline gluteraldehyde solutions on the strength (failure load) and the required displacement or stretching to achieve a force of 500g was studied for six types of elastomeric chains. The effect of disinfection (short-term exposure) and sterilization (long-term exposure) as well as repeated immersion cycles on these parameters was evaluated. The findings showed that exposure to gluteraldehyde solution affected the strength and the distention required to deliver a force of 500g of certain elastomeric chains. However, the resultant changes were relatively small and are probably insignificant in the clinical setting. PMID- 1901465 TI - Establishment of dose-response relationships in BALB/c mice, using Brucella cell surface protein and lipopolysaccharide. AB - A study was conducted to determine the immune (increased antibody) and protective (reduced colony-forming units) responses induced in mice by a: (i) single vaccinal inoculation, using various concentrations of Brucella cell surface protein (BCSP) or lipopolysaccharide (LPS); (ii) primary inoculation, using various concentrations of BCSP, followed by a secondary inoculation, using a standard concentration of BCSP; and (iii) primary inoculation, using 1 concentration of BCSP or LPS, followed by a secondary inoculation, using various concentrations of BCSP or LPS. Four weeks after the primary inoculation, mice were challenge exposed with approximately 1 x 10(4) colony-forming units of Brucella abortus strain 2308 and all mice were euthanatized at 6 weeks. Reduced splenic weights and reduced colony-forming units in the spleens of vaccinated mice, compared with nonvaccinated mice, were the criteria of protection. Increase in serum IgM and IgG was defined as immunity. Both BCSP and LPS induced protective and immune responses that were proportional to the dose given up to an optimal limit. However, concentrations higher than optimal decreased the protective and immune responses. This was true for mice given either 1 or 2 vaccinal inoculations. Enhanced secondary protective responses were seen only when suboptimal doses were used in the primary inoculation. Excessive or optimal doses in the secondary inoculations prevented or obscured the protectiveness and immunity by primary inoculations. The protective effects appeared to be additive when suboptimal doses were used in the primary and secondary inoculations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1901466 TI - Intracerebral hemorrhage related to cerebral amyloid angiopathy and t-PA treatment. AB - Tissue plasminogen activator (t-PA) has been approved as thrombolytic therapy for the treatment of acute myocardial infarction, but this agent can cause serious bleeding complications including intracerebral hemorrhages. Mechanisms underlying the development of these hemorrhages have not been clarified. We report a patient who developed two intracerebral hemorrhages shortly after receiving t-PA for the treatment of an acute myocardial infarction, and who was found to have cerebral amyloid angiopathy at autopsy. Staining of cortical sections with Congo red and an antibody directed against beta amyloid protein (A4 peptide) disclosed specific involvement of most of the subarachnoid and superficial cortical vessels in the region of the two hemorrhages. Based on the findings in this patient and in 6 additional patients reported recently, it is likely that cerebral amyloid angiopathy plays a pathogenic role in some intracerebral hemorrhages associated with the administration of t-PA. The cautious use of t-PA with heparin in patients who are elderly or demented may be advisable. PMID- 1901467 TI - Silence as a feminist and nursing issue. PMID- 1901468 TI - Is health care racist? PMID- 1901469 TI - Voices and paradigms: perspectives on critical and feminist theory in nursing. AB - Nurse scientists have explored a variety of research methods and a number of philosophic approaches to expand the discipline's ability to describe and investigate nursing's phenomena of interest. This article discusses the similarities and differences in world views, epistemologies, methodologies, and methods of two of these paradigms: critical theory and feminist theory. Attributes of these two stances are contrasted, and the relationship between the methods of analysis and the philosophic point of view are explored. An example of nursing research is given, with discussion of how the approach would differ if the nurse scientist were using critical versus feminist theory as a frame of reference. PMID- 1901470 TI - Rigor in feminist research. AB - Verifying the scientific adequacy of feminist studies is necessary to assure that research processes and outcomes are well grounded, cogent, justifiable, and relevant. The authors analyze what scientific adequacy means in feminist inquiry and propose standards of rigor by which nurse investigators can plan and evaluate their studies. In the process, conventional empiricist criteria of reliability and validity are critiqued, and more appropriate concepts representing dimensions of adequacy in feminist research are presented. PMID- 1901471 TI - Exploring gender and culture with Khmer refugee women: reflections on participatory feminist research. AB - This article discusses the process and findings from a study based on the paradigm of feminist participatory research. The research is first discussed in relation to contemporary feminist scholarship. The project combined elements of community health nursing practice and feminist research in a support group with Khmer refugee women. The research explored psychosocial adjustment and the construction of gender among Khmer women. Methods of data collection included life history and trauma history interviews, discussion of dream narratives and Cambodian myths, and participant observation. Findings included four recurring themes identified in the women's stories. The research process is discussed in terms of its implications for nursing praxis. PMID- 1901472 TI - Feminist nursing research without gender. AB - This theoretic article examines the potential for different types of nursing research to reinforce or undermine gender categories that historically have served to limit some women and marginalize others. Feminist research that gathers or analyzes information in the form of a male/female or man/woman dichotomy risks reproducing social relations damaging to women. Other approaches to dispersing or deconstructing gender dichotomies are discussed, and a series of questions about feminist nursing research is raised. PMID- 1901473 TI - Feminist theory and nursing: an empowerment model for research. AB - This article describes the use of the feminist process to empower nurses in conducting research. The criteria for feminist research, defined by Duffy, are applied to a research study that identifies the effects of physical abuse during pregnancy on maternal-infant outcomes. The authors describe the process of empowerment of the investigators through the use of a consortium model of research, the staff nurses who are conducting the interviews, and the research participants (pregnant women). The integration of feminist principles and nursing research is a process that merges similar beliefs and ideologies. PMID- 1901474 TI - [Chemoembolization with degradable starch microspheres for liver metastases of colorectal cancer]. AB - Transcatheter chemoembolization using degradable starch microspheres (DSM) was performed in 17 patients with liver metastases of colorectal cancer. DSM, 45 microns in diameter, which are easily degraded by serum amylase, and therefore obstruct arterial blood flow temporarily at the arteriolar capillary bed. DSM mixed with mitomycin C were administered through the catheter introduced by Seldinger's method in 13 cases, and through subcutaneously implanted drug delivery system (Port-A-Cath) in 4 cases. The treatment was repeated 5 times on the average at intervals of 2 to 4 weeks. The therapeutic effect of this chemoembolization was evaluated by the change in tumor size measured by angiography or computed tomography. Tumor regression of over 50% was observed in 9 of 17 cases (53%). Elevated serum CEA levels (greater than 10 ng/ml) decreased in 10 of 15 cases (67%). One-year survival rate was 48% in 17 cases, and among them it was 100% in 7 cases with the extent of several liver metastases (H2). Extrahepatic metastasis was observed in 3 of 17 cases (18%) before the treatment, and in 8 cases (47%) after the treatment. Abdominal pain occurred in 36% of the cases by the administration of DSM, but the pain disappeared within 2 hours. No major side effects such as bone marrow suppression or hepatotoxicity were observed. Our results suggest that chemoembolization using DSM is effective and safe in the treatment of liver metastases from colorectal cancer. PMID- 1901475 TI - [Growth chamber assay, a novel chemosensitivity test which eliminates normal stromal cells]. AB - The chemosensitivity test with growth chamber (GC), a semi permeable polymer matrix, was conducted using human tumor xenografts, comparing the results with those of in vivo nude mouse system. Xenografts used were MX-1, St-4, Co-3, and Co 4. Normal stromal cells, SM-74, a cell line derived from human adult skin fibroblast, and Clone-A-31, a cell line from BALB/c nu/nu nude mice were used as the control. Dissociated tumor cell suspension in 200 microliters of Medium 199 was plated into GC (80,000 cells, chamber) and incubated with a various concentration of mitomycin C(MMC), cisplatin (DDP), 5-fluorouracil (5-FU), and adriamycin (ADM) at the various concentrations. After incubation of 1 wk, the activity of hexosaminidase was measured with ELISA assay using p-nitrophenyl-N acetyl-glucosaminide. The antitumor activity of the agents against human tumor xenografts was dose dependent, and the antitumor spectra obtained by GC assay was essentially identical to in vivo nude mouse system. On the other hand, no evaluable optical density could be obtained with normal stromal cells, SM-74 and Clone-A-31. The optimal cutoff concentration of each drugs to predict the in vivo results was estimated to be 10 micrograms/ml for MMC, 15 micrograms/ml for DDP and 5-FU, and 0.7 microgram/ml for ADM. The predictability of GC assay was 77%, including 89% sensitivity and 70% specificity. Since GC assay could eliminate the normal stromal cells because of the characteristic of chamber surface, this assay was thought to be useful for the clinical chemosensitivity test of human cancers containing a large number of normal stromal cells. PMID- 1901476 TI - [Clinical evaluation of bronchial artery infusion (BAI) in lung cancer]. AB - Clinical evaluation of 32 cases of primary lung cancer treated with Bronchial Artery Infusion (BAI) were reported. As to the relationship between Bronchial Arteriogram (BAG) and therapeutic effect of BAI, the therapeutic effect of BAI was closely correlated with the degree of neovascularity. And as no correlation was shown between therapeutic effect and histology of lung cancer, the degree of neovascularity on BAG seemed to be more important factor. From the aspect of survival, neovascularity and B-P shunt on BAG showed no correlation with the survival time. On the relationship between survival and histology of lung cancer, squamous cell carcinoma and adenocarcinoma showed almost an equivalent survival. According to the stage of our cases, 25 out of 32 cases were stage III and IV, and they showed relatively better survival, especially stage III, of which MST was 16.6 months, and of which a two year survival rate was 33.5% considering MST and a two year survival rate of stage III A (N2) of non-resected non-small cell lung cancer in other reports are about 12 months and 20%, respectively. BAI is considered to be an effective method among several treatments against lung cancer. PMID- 1901477 TI - [Total body hyperthermia and continuous hyperthermic peritoneal perfusion as an adjuvant therapy in advanced gastric cancer]. AB - Between September 1986 and July 1989, adjuvant hyperthermic therapy, consisting of either total body hyperthermia (TBHT) or continuous hyperthermic peritoneal perfusion (CHPP), was given to a total of 41 patients immediately following gastric resection for cancer. TBHT was performed in 1 curative- and 11 noncurative-gastrectomized patients (1 stage III and 11 stage IV), and CHPP in 18 curative- and 11 noncurative-gastrectomized patients (6 stage I/II, 10 stage III and 13 stage IV). For TBHT, the blood was warmed and maintained at 42 degrees C for 3 hours by means of a V-V bypass connected to an extracorporeal heater pumping system. When the hyperthermic condition was established, anti-cancer drugs were administered intravenously. In CHPP, 46 degrees C saline containing anti-cancer drugs were infused at a constant rate through a tube placed at the Douglas fossa. The perfusate was drained out through another tube positioned at an uppermost part of the abdominal cavity. The hyperthermic condition was monitored by measuring the outflow temperature. Complications encountered were bone marrow depression, liver damage and pyrexia, and were more frequently experienced by the TBHT patients. Patients under 65 years of age who had had an absolute noncurative gastrectomy but with TBHT survived significantly longer than those without TBHT. When the patients who had undergone gastrectomy with CHPP for a cancer of more than se penetration were compared with those without CHPP, there was no significant difference in survival found between these two populations. This unsatisfactory result could be partly attributable to difficult maintenance of appropriate (sufficiently high) and constant perfusate temperature. PMID- 1901479 TI - Prolonged pumpless arteriovenous perfusion for carbon dioxide extraction. AB - A method of extracorporeal carbon dioxide extraction from the blood using an efficient microporous membrane oxygenator or membrane gas exchanger was evaluated during pumpless arteriovenous perfusions with a view to its application for partial respiratory support. The first study carried out in dogs revealed some increase in cardiac output, cardiac index, and cardiac work, although this increase was less than that normally expected from the added extracorporeal blood flow. In sheep during 3 to 7 days of continuous bypass, there was practically no hemolysis and relatively stable hemoglobin and hematocrit levels, and the platelet counts remained within safe levels. The maximum extracorporeal blood flow tended to decrease from a mean of 1.55 L/min on day 1 to 1.34 L/min on day 3 to 1.28 L/min on day 7. Carbon dioxide extraction remained efficient throughout the perfusion, but there was a minimal decrease from the first day (10.92 mmol/L) to the third day (8.46 mmol/L) at the higher blood carbon dioxide concentrations; it remained stable thereafter at 9.0 mmol/L. PMID- 1901478 TI - [Clinical experiences with hyperthermochemotherapy of hepatic metastasis from gastric cancer]. AB - Thermochemotherapy was performed on gastric cancer cases of hepato-metastasis. The subjects were 12 gastric cancer cases having hepato-metastatic lesions (10 synchronous, 2 heterochronous). Using 8 or 13.58 MHz-dielectric heating apparatus, thermotherapy was carried out for 40-60 min (twice a week, 5-35 times, averaging 12.8 per case) at an intra-tumoral temperature greater than 42 degrees C. Chemotherapy consisted of hepato-arterial infusion of MMC 10 mg/BW, CDDP 75 mg/m2 once per 3-4 weeks and consecutive daily administration p.o. of UFT 800 mg/BW. Effect greater than PR was noted in 75% (9/12) on the whole and in 100% (5/5) and 57% (4/7) for H1-2 and H3, respectively. Mean and 50% survival periods were 9.3 and 7.2 months, respectively, with a one-year survival rate of 38%. Chemotherapy-induced side effects were nausea and vomiting in 83% and leukopenia and thrombopenia in 67%, while the only thermotherapy-induced side effect was subcutaneous fatty tissue necrosis in 3 cases. The above results suggested the effectiveness of the present thermochemotherapy in the treatment of hepato metastasis of gastric cancer. PMID- 1901480 TI - Surgical treatment of the Wolff-Parkinson-White syndrome by epicardial electrical ablation. AB - A new operation to eliminate accessory pathways--epicardial electrical ablation- is described. In a group of 201 patients without concomitant disease, the mortality rate was 0.5% and the overall efficacy of the operation for free wall accessory pathways, 98%. A retrospective clinical study of 44 unselected patients was performed to examine how safe epicardial electrical ablation is. The criteria for intraoperative effectiveness were disappearance of both the delta wave and retrograde conduction and inability to induce tachycardia. In the postoperative and follow-up periods, the following were reviewed: electrocardiograms; Holter monitor recordings (24 to 26 hours); release of the myocardial-specific isoenzyme of creatine kinase; intracardiac hemodynamics and myocardial contractility (radionuclide methods); selective coronary arteriograms and ventriculograms; mean work capacity (bicycle ergometer); diagnostic transesophageal electrical stimulation; and histology of the area of ablation. The main conclusion of this study is that epicardial electrical ablation is a highly efficient and safe operation for surgical elimination of parietal accessory pathways in patients with Wolff-Parkinson-White syndrome. Its advantages are its technical simplicity and the opportunity to review results immediately during the operation. PMID- 1901481 TI - Growth of tracheal anastomoses: advantage of absorbable interrupted sutures. AB - Growth of the trachea after complete transection and anastomosis was studied in four groups of 1-month-old New Zealand white rabbits. The trachea was transected at the fifth cartilaginous ring and then anastomosed with continuous 6-0 polypropylene (Prolene) (group 1), interrupted 6-0 polypropylene (group 2), continuous 6-0 polydioxanone (PDS) (group 3), or interrupted 6-0 PDS (group 4). The animals were followed up for 90 to 103 days (mean follow-up, 95 days). At the time the animals were killed, body weight had increased 125% (1.2 to 2.7 +/- 0.18 kg). Growth of the trachea was assessed at the time of death. Results from this study suggest that growth of a tracheal anastomosis is retarded in a growing animal model. The degree of resultant stenosis was significantly less when an absorbable suture material (PDS) and an interrupted suturing technique were used. PMID- 1901482 TI - Low-dose intermittent trimethoprim-sulfamethoxazole for prevention of Pneumocystis carinii pneumonia in patients with human immunodeficiency virus infection. AB - The important role of chemoprophylaxis for the prevention of Pneumocystis carinii pneumonia (PCP) in human immunodeficiency virus type 1 (HIV)-infected patients is undisputed. The most cost-effective regimen, however, is unknown. We reviewed our experience at two hospitals in the New York City area in which low-dose, intermittent therapy with the combination of trimethoprim and sulfamethoxazole was used to prevent PCP in HIV-infected patients. During a total of 202 months of primary prophylaxis in 32 patients and 319 months of secondary prophylaxis in 35 patients, PCP was diagnosed only once. More than 80% of patients were receiving zidovudine concomitantly. Adverse reactions to trimethoprim-sulfamethoxazole occurred in 31% and 52% of those receiving primary or secondary prophylaxis, respectively. When those patients who were considered ineligible to receive trimethoprim-sulfamethoxazole prophylaxis (principally based on a prior adverse drug reaction) are also factored in, then approximately 50% of HIV-infected patients are candidates for long-term trimethoprim-sulfamethoxazole prophylaxis. The projected cost savings of this prophylaxis regimen, compared with those currently recommended by the US Public Health Service, are enormous. PMID- 1901483 TI - Storage of thawed cryoprecipitated AHF is better at room temperature than at 1 degree C to 6 degrees C for factor VIII content. AB - Before November 1989, both the American Association of Blood Banks and the Food and Drug Administration required that thawed cryoprecipitated antihemophilic factor (AHF) should be used immediately or be stored at room temperature and administered within 6 hours. However, in November 1989, the American Association of Blood Banks changed the requirement for storage of thawed cryoprecipitated AHF from room temperature to 1 degree C to 6 degrees C, while the Food and Drug Administration still required thawed cryoprecipitated AHF to be stored at room temperature. The present study was designed to measure and compare the factor VIII activity in 10 bags of thawed cryoprecipitated AHF that were split into aliquots and stored at room temperature and at 1 degree C to 6 degrees C. At 6 and 24 hours after thawing, the mean factor VIII activities (% of normal) of the room temperature-stored cryoprecipitated AHF were 741% and 680% vs 650% and 608% for the 1 degree C- to 6 degrees C-stored cryoprecipitated AHF (P less than .05 at 6 hours and P = .11 at 24 hours). The storage of thawed cryoprecipitated AHF at 1 degree C to 6 degrees C also resulted in precipitation of both factor VIII and fibrinogen. These data show that it is better to store thawed cryoprecipitated AHF at room temperature vs 1 degree C to 6 degrees C for factor VIII activity. These data also suggest that adequate levels of factor VIII are maintained in thawed cryoprecipitated AHF that has been stored at room temperature for up to 24 hours. PMID- 1901484 TI - Positron emission tomography in progressive supranuclear palsy. AB - Positron emission tomography with 6-[18F]fluoro-L-dopa (6-FD) provides in vivo information on the function of nigrostriatal dopaminergic neurons. We used 6-FD and positron emission tomography to investigate the integrity of the nigrostriatal system in seven patients with progressive supranuclear palsy. All patients had axial hypertonia, vertical gaze palsy, and parkinsonian features. Dementia, pyramidal signs, and ataxia were seen in varying proportions. We analyzed the scans with a graphic method to calculate a steady-state 6-FD uptake rate constant for the whole striatum. Results were compared with those obtained in seven age-matched controls. As a group, the patients with progressive supranuclear palsy had reduced 6-FD uptake constants. The 6-FD uptake constant correlated inversely with the duration of the disease. Normal positron emission tographic findings in one patient with the shortest duration of symptoms suggests that in early progressive supranuclear palsy, parkinsonism may relate to dysfunction distal to the dopaminergic neurons. PMID- 1901485 TI - Late-infantile type galactosialidosis. Histopathology of the retina and optic nerve. AB - We studied histopathologic findings from the retina and optic nerve of a patient with the late-infantile type of galactosialidosis and related them to clinical features of the condition. Markedly fewer ganglion cells were evident histopathologically using light microscopy. Results of histochemical studies demonstrated abnormal accumulation of lipid and proteinaceous material in the residual swollen ganglion cells. Marked loss of myelinated nerve fibers and thickening of the pial septum were also observed in the optic nerve. Both retinal ganglion cells and amacrine cells had intracytoplasmic inclusion bodies, but none were found in the optic nerve. These findings suggested that optic atrophy was induced by axonal wallerian degeneration secondary to retinal ganglion cell death. Although the fundus showed advanced optic nerve atrophy, a cherry red spot was not evident, possibly because of the marked decrease in ganglion cells in this case. PMID- 1901486 TI - Streptococcus sanguis survival in K-Sol. Comparison of gentamicin and the fluoroquinolone antibiotics. AB - Viridans streptococci are poorly covered by gentamicin sulfate in corneal storage medium. To evaluate possible antibiotic alternatives among the newer broad spectrum fluoroquinolone antibiotics, we compared the survival of the viridans representative Streptococcus sanguis in K-Sol with gentamicin sulfate (100 mg/L), norfloxacin (250 mg/L), ciprofloxacin lactate (250 mg/L), ofloxacin (250 mg/L), or no antibiotic. At 23 degrees C, K-Sol with gentamicin produced a 2-log kill by 80 minutes. By comparison, only one of the others (norfloxacin) had achieved a 2 log kill by 4 hours. At 4 degrees C, all antibiotics differed little from the control, and none was superior to gentamicin. PMID- 1901487 TI - Social determinants of cataract surgery utilization in south India. The Operations Research Group. AB - A field trial was conducted to compare the effects of eight health education and economic incentive interventions on the awareness and acceptance of cataract surgery. Cataract screening and follow-up surgery were offered to more than 19,000 residents age 40 years and older in a probability sample of 90 villages in south India. Eight months after intervention, an evaluation was conducted to identify those in need of surgery who had been operated on. Two principal measures of program effectiveness are examined: awareness of cataract surgery and acceptance of the surgery. The type of intervention had a negligible effect on awareness of cataract surgery. A multiple logistic regression analysis revealed that individuals who were aware of surgery tended to be male, literate, and more affluent than those who were unaware of that option. Interventions that covered the complete costs of surgery had higher surgery acceptance rates. One health education strategy, house-to-house visits by a subject with aphakia, increased acceptance of the procedure more than others. In a multiple logistic regression analysis of acceptance rates, persons accepting surgery tended to be male; other factors were not important in explaining variation in acceptance rates. PMID- 1901488 TI - Albino mutants of Streptomyces glaucescens tyrosinase. AB - Site-directed mutagenesis was used to determine the functional role of several residues of Streptomyces glaucescens tyrosinase. Replacement of His-37, -53, -193 or -215 by glutamine yields albino phenotypes, as determined by expression on melanin-indicator plates. The purified mutant proteins display no detectable oxy enzyme and increased Cu lability at the binuclear active site. The carbonyl derivatives of H189Q and H193Q luminesce, with lambda max. displaced more than 25 nm to a longer wavelength compared with native tyrosinase. The remaining histidine mutants display no detectable luminescence. The results are consistent with these histidine residues (together with His-62 and His-189 reported earlier) acting as Cu ligands in the Streptomyces glaucescens enzyme. Conservative substitution of the invariant Asn-190 by glutamine also gives an albino phenotype, no detectable oxy-enzyme and labilization of active-site Cu. The luminescence spectrum of carbonyl-N190Q, however, closely resembles that of the native enzyme under conditions promoting double Cu occupancy of the catalytic site. A critical role for Asn-190 in active-site hydrogen-bonding interactions is proposed. PMID- 1901489 TI - Light-dependent de-activation/re-activation of Anabaena variabilis ferredoxin: NADP+ reductase. AB - The activity of ferredoxin: NADP+ reductase (FNR) was found to decline to approximately 20% maximal levels with little or no loss in enzyme levels when cultures of the cyanobacterium Anabaena variabilis were maintained in the stationary phase of growth. Re-activation of enzyme activity occurred when cells were diluted into either fresh or re-utilized media and illuminated. This reversible de-activation/re-activation process was found, in vivo, to be dependent on the intensity of light illuminating the cells. The de-activated form of FNR was purified to homogeneity and exhibited the same molecular mass, isoelectric-focusing pattern and N-terminal amino acid sequence as the native form. Both de-activated and native FNR preparations each exhibited three reactive thiol groups on denaturation in urea; however, the rate of reaction with Ellman's reagent was much faster with the de-activated form than with the native form. Both preparations contain a single disulphide bond. Upon reduction of the disulphide bond in either form of the enzyme, the five reactive thiol groups exhibited identical reactivities in the presence of urea. Steady-state kinetic analysis of the de-activated form showed a marked increase in Km values for NADPH in diaphorase assays and an increase in Km for ferredoxin in the ferredoxin mediated reduction of cytochrome c. No significant difference in kcat. was observed in comparison of the de-activated with the native form in any of the above assays; however, the de-activated form did exhibit a lower kcat. value in the transhydrogenase assay. The de-activated form of FNR bound ferredoxin with a 16-fold lower affinity than the native enzyme. These data suggest that the de activation of FNR in vivo in response to low light intensity involves an alteration in protein structure, possibly via an intramolecular thiol disulphide interchange, which influences the interaction of the enzyme with its substrates. PMID- 1901490 TI - Dimeric carotenoid interaction in the light-harvesting antenna of purple phototrophic bacteria. AB - The carotenoid content of intracytoplasmic membrane vesicles isolated from purple phototrophic bacteria was reduced to a variable extent by mild extraction with light petroleum. Using preparations obtained from Rhodobacter capsulatus strains that contained the Light Harvesting System I (LHI) complex as the only major photosynthetic holochrome, it was shown that the visible circular dichroism of the carotenoids increased with the square of the membrane carotenoid content, as expected from being caused by dimeric exciton interaction. No chirality resulting from twists of the individual planar chromophore was detected. Therefore the contribution to carotenoid optical activity of non-degenerate interactions with bacteriochlorophyll or the apoprotein does not appear to be significant. The broadening of the absorption band of the bound pigment, caused by the splitting of the monomer transition, was demonstrated in membrane vesicles of both Rb, capsulatus and Rhodospirillum rubrum as a decrease of the fine structure of the band. Furthermore, the dimeric organization of the carotenoid pigments in the bacterial LHI complex accounted for the observed quantitative relationship between the fine structure of the band and the carotenoid content of the membrane. PMID- 1901491 TI - Predictors of survival in systemic sclerosis (scleroderma). AB - We conducted followup of 264 patients with definite systemic sclerosis (SSc) who were entered into the multicenter Scleroderma Criteria Cooperative Study (SCCS) during 1973-1977. At the end of the study (average 5.2 years of followup), 38% were known to be alive, 50% were dead (68% of these deaths definitely related to SSc), and 12% were lost to followup. Survival analyses of 484 demographic, clinical, and laboratory items recorded at entry into the SCCS (within 2 years of physician diagnosis of SSc) were performed. Survival declined linearly, and the cumulative survival rate was less than 80% at 2 years, 50% at 8.5 years, and 30% at 12 years after entry. Analysis using combinations of entry variables identifying organ system involvement confirmed that renal, cardiac, pulmonary, and gastrointestinal involvement in SSc predicted reduced survival; however, data on organ system involvement at study entry could not be used to consistently predict which organ system would ultimately be involved as the primary cause of death. By survival tree analysis, the individual entry variables best predicting reduced survival included older age (greater than 64 years), reduced renal function (blood urea nitrogen greater than 16 mg/dl), anemia (hemoglobin less than or equal to 11 gm/dl), reduced pulmonary diffusing capacity for carbon monoxide (less than or equal to 50% of predicted), reduced total serum protein level (less than or equal to 6 gm/dl), and reduced pulmonary reserve (forced vital capacity less than 80% with hemoglobin greater than 14 gm/dl or forced vital capacity less than 65% with hemoglobin less than or equal to 14 gm/dl). Cox proportional hazards model analysis confirmed these results. Different combinations of variables led to markedly different survival rates. The poorest prospects for survival were in patients with SSc who were less than or equal to 64 years old with a hemoglobin level less than or equal to 11 gm/dl, and in those greater than 64 years old with a blood urea nitrogen level greater than 16 mg/dl. These results may be useful in predicting individual patients at risk for shortened survival. PMID- 1901493 TI - [A case of simple partial seizure controlled with oxcarbazepine]. PMID- 1901492 TI - Magnetic resonance imaging of central nervous system lesions in patients with lupus erythematosus. Correlation with clinical remission and antineurofilament and anticardiolipin antibody titers. AB - Clinical, magnetic resonance imaging (MRI), and serologic studies were performed on 11 patients with diffuse central nervous system (CNS) systemic lupus erythematosus and 8 patients with focal CNS lupus. MRI of patients with diffuse clinical disease showed symmetrically distributed areas of increased signal intensity in the subcortical white matter; these resolved after treatment with high-dose methylprednisolone. These patients' sera contained elevated levels of antineurofilament antibodies. Patients with focal CNS lupus had areas of increased signal intensity and atrophic changes in regions corresponding to the major cerebral vessels. These MRI abnormalities did not improve after treatment with high-dose steroids. The sera of patients with focal CNS lupus had elevated levels of cardiolipin and lupus anticoagulant but normal levels of antineurofilament antibody. Our findings suggest that results of a combined clinical, MRI, and serologic evaluation of patients with CNS lupus may predict the response of patients to high-dose steroid therapy. PMID- 1901494 TI - Towards the development of improved thrombolytic agents. PMID- 1901496 TI - Bilateral retinal hamartomas in neurofibromatosis type 2. AB - We report a case of bilateral retinal hamartomas in a child with neurofibromatosis type 2. This unique case demonstrates that a diversity of retinal changes can occur in this disease. PMID- 1901495 TI - Interferon-gamma in vivo reverses the increased platelet levels of platelet derived growth factor and transforming growth factor-beta in patients with myelofibrosis with myeloid metaplasia. AB - We previously reported high platelet-derived growth factor (PDGF) and transforming growth factor beta (TGF-beta) levels in platelets from patients with myelofibrosis with myeloid metaplasia. We report here the effects of in vivo administration of recombinant human interferon-gamma on these growth factor levels. Of six patients who entered this study in our institution, four completed the 6-month therapy trial with interferon-gamma PDGF and TGF-beta levels in platelets were evaluated before and after treatment. PDGF levels were determined using a radioimmunoassay and TGF-beta activity was measured using an inhibition growth assay on CC164 cells. In these four patients, IFN-gamma therapy led to a reduction of the increased PDGF and TGF-beta levels in platelets towards the normal range. PDGF and TGF-beta values decreased by 25-45% and 32-46%, respectively. An acute deterioration was observed in one patient 5 months after the end of IFN-gamma therapy. In this patient, the deterioration of his clinical state correlated with an increase in intraplatelet PDGF and TGF-beta levels. PMID- 1901497 TI - Aerosolized gamma-interferon and lipopolysaccharide enhances cytotoxicity of murine pulmonary alveolar macrophages. AB - In vivo stimulation of pulmonary alveolar macrophages (PAMs) may enhance tumor cell cytotoxicity. A model using aerosolized gamma-interferon (gamma-IFN) and lipopolysaccharide (LPS) was developed to induce enhanced PAM activation in vivo in C57BL/6 mice. Mice received four doses of aerosol (2 doses/day) consisting of gamma-IFN (10(4) microU/mouse) and LPS (100 micrograms/mouse). Other groups received either gamma-IFN alone, LPS alone, or saline (control). Cells were harvested by bronchoalveolar lavage. Macrophage cell count demonstrated an increase in macrophage recruitment in the gamma-IFN and LPS group. PAMs were evaluated for in vitro cytotoxicity against B16-F10 melanoma cells. Treatment groups demonstrated enhanced cytotoxicity over controls, and the combination (gamma-IFN plus LPS) was significantly better in cell killing than either treatment modality alone (p less than or equal to 0.02). Activated PAMs selectively killed tumor cells, but did not kill the 3T3 fibroblast cell line. Peritoneal macrophages from mice treated by inhalational gamma-IFN + LPS were enhanced (indicating a systemic effect), but not to the same extent as PAMs. These studies suggest that inhalation of gamma-IFN + LPS can selectively enhance in vivo cytotoxicity of murine PAMs. This may potentially be applicable to human tumor management. PMID- 1901498 TI - Small unilamellar vesicles are able to fuse with Mycoplasma capricolum cells. AB - We have investigated the fusion characteristics of intact Mycoplasma capricolum cells and small unilamellar vesicles (SUV). The rate and extent of fusion was monitored continuously by octadecylrhodamine B (R18) fluorescence dequenching assay, as well as by intracellular contents mixing, and by sucrose density gradient analysis. The fusion of SUV with M. capricolum cells was found to be dependent on poly(ethylene glycol) (PEG 8000), divalent cations in the medium, and on the cholesterol content of the lipid vesicles. Maximal levels of fusion were obtained with SUV containing 40 mol% cholesterol in the presence of 5% PEG. The rate and extent of fusion were affected by temperature, pH, osmotic pressure, and SUV/mycoplasma ratio. Under optimal fusion conditions, PEG did not increase the rate of exchange of either cholesterol or phospholipids between M. capricolum cells and SUV. Throughout the fusion process, M. capricolum cells remained intact as measured by the retention of [3H]thymidine-labeled components, and viable. M. capricolum cells were rendered nonfusogenic by treatment with glutaraldehyde (greater than 0.01%) or chlorpromazine (greater than 10 microM). Fusion was partially inhibited by treating the cells with the uncoupler CCCP (5 microM) or proteolytic enzymes, suggesting that a proton gradient across the cell membrane is required for the fusion, and that the cells possess proteinase-sensitive receptors that are responsible for a tighter contact with the lipid vesicles. PMID- 1901499 TI - Localization of the N-terminal methionine of rat liver cytochrome P-450 in the lumen of the endoplasmic reticulum. AB - Recent cumulative evidence suggests that liver microsomal cytochrome P-450 (P 450) is exposed to the cytosol with the exception of the N-terminal peptide (amino acid residues 1 to 21), or two peptides (residues 1 to 60). We tested the localization of the N-terminal methionine residue of P-450IIB1 of rat liver microsomes in the natural membrane with the site-specific reagent fluorescein isothiocyanate. The N-terminus of isolated P-450 was stoichiometrically modified in solution with fluorescein isothiocyanate. In intact microsomes, the N-terminus was not modified but became accessible to the reagent when the membrane was dissolved with Triton X-100. Our results indicate that the N-terminus faces the lumen of the endoplasmic reticulum, and we propose that P-450 spans the membrane only once with amino acid residues 1 to 21. PMID- 1901500 TI - Corneal deposits associated with flecainide. PMID- 1901502 TI - "Difficult to place" psychiatric patients. PMID- 1901501 TI - Role of general practitioners in care of long term mentally ill patients. AB - OBJECTIVE: To assess general practitioners' involvement with long term mentally ill patients and attitudes towards their care. DESIGN: Postal questionnaire survey. SETTING: General practices in South West Thames region. SUBJECTS: 507 general practitioners, 369 (73%) of whom returned the questionnaire. MAIN OUTCOME MEASURES: The number of adult long term mentally ill patients whom general practitioners estimate they have on their lists and general practitioners' willingness to take responsibility for them. RESULTS: 110 respondents had noticed an effect of the discharge of adult long term mentally ill patients on their practices. Most (225) respondents estimated that they had 10 or fewer such patients each on their lists. Having higher numbers was significantly associated with practising in Greater London or within three miles of a large mental hospital and having contact with a psychiatrist visiting the practice. 333 general practitioners would agree to share the care of long term mentally ill patients with the psychiatrist by taking responsibility for the patients' physical problems. Only 59 would agree to act as a key worker, 308 preferring the community psychiatric nurse to do it. Only nine had specific practice policies for looking after long term mentally ill patients and 287 agreed that such patients often come to their general practitioner's attention only when there is a crisis. CONCLUSIONS: The uneven distribution of long term mentally ill patients suggests that community pyschiatric resources might be better targeted at those practices with higher numbers of such patients. Most general practitioners seem to be receptive to a shared care plan when the consultant takes responsibility for monitoring psychiatric health with the community nurse as key worker. The lack of practice policies for reviewing the care of long term mentally ill patients must limit general practitioners' ability to prevent crises developing in their care. PMID- 1901503 TI - The psychiatric symptoms, diagnoses and care needs of 100 mentally handicapped patients. AB - One hundred randomly selected residents of a mental handicap hospital originating from Dundee were interviewed using a standardised assessment based on the modified Standardised Clinical Interview Schedule. Information on certain behavioural items and self-care skills was obtained from nursing staff and case records. An ICD-9 diagnosis could be made for 80 individuals, including diagnoses usually reserved for children. Thirty subjects were regarded as needing long-term psychiatric mental handicap hospital care. All but one of the remaining 70 subjects required a staffed residential placement and all but 15 some form of out patient or short-term in-patient provision from specialist health services. The findings indicate a need for approximately 30 psychiatric mental handicap beds per 100,000 population. PMID- 1901504 TI - Antiparkinson-like effects of neurotensin in 6-hydroxydopamine lesioned rats. AB - The aim of the present study was to examine the effects of neurotensin in an animal model of Parkinson's disease (PD). Bilateral administration of 6-OHDA in the medial forebrain bundle at the level of the posterolateral hypothalamus of rats resulted in the appearance of the 3 principal neurological signs of PD: hypokinesia, rigidity and tremor. These symptoms were accompanied by severe losses of dopamine and its main metabolites in terminal regions of well-known dopamine pathways. Norepinephrine concentrations were also decreased in several regions but to a lesser extent than dopamine. Intracerebroventricular administration of neurotensin, in doses ranging from 7.5 to 120.0 micrograms, resulted in dose related attenuations of both muscular rigidity and tremors of animals. However, hypokinesia, defined as decreased motor activity was not significantly affected by the peptide. Administration of 120.0 micrograms of [Ala]NT, an inactive analogue of neurotensin, failed to alter any of the 3 neurological signs. Together, these results reveal selective antiparkinson-like effects of neurotensin in an animal model. The theoretical significance of these findings is discussed. PMID- 1901505 TI - Alteration of phrenic high frequency oscillation by local cooling of the ventral medullary surface. AB - Cooling of small sites on the ventral medullary surface of the cat produces a decrease in frequency of phrenic high frequency oscillation (HFO). The effect on HFO frequency of cooling near the hypoglossal rootlets, but not the effect of cooling near the inferior cerebellar artery, can be completely offset by raising arterial pCO2 to restore phrenic activity to its precooling level. Thus, structures near the ventral medullary surface are important for generation or propagation of phrenic HFO. The effect of cooling of the 'intermediate area' cannot be entirely explained as depression of putative central chemoreceptor activity. PMID- 1901506 TI - Halothane enhances tonic neuronal inhibition by elevating intracellular calcium. AB - Whether the major action of anesthetics is to depress the central nervous system (CNS) by reducing excitation or enhancing inhibition remains unknown. Using whole cell patch-clamp recording in hippocampal slices, halothane and pentobarbital were found to prolong the decay time constant (TAU(D)) of GABAA-mediated spontaneous inhibitory postsynaptic currents (sIPSCs). Intracellular administration of the Ca2+ chelator BAPTA or the Ca2+ release inhibitor dantrolene significantly (ANOVA, P less than 0.005) reduced halothane's effect; in contrast, the pentobarbital effect was unchanged. Halothane induced depression of population spike amplitude was blocked by the GABAA antagonist bicuculline. Together, these findings suggest that a major depressant effect of halothane involves enhancement of GABAA-mediated inhibition through release of intraneuronally stored Ca2+. PMID- 1901507 TI - Effects of photoperiod and hypothalamic knife cuts on the timing of FSH surges in hamsters. AB - The timing of the proestrous surge of follicle-stimulating hormone (FSH) was examined in female hamsters with hypothalamic knife cuts that prevented reproductive responses to photoperiod. All animals received either a horizontal knife cut aimed between the suprachiasmatic nuclei (SCN) and the paraventricular nuclei (PVN), or sham surgery, and were housed in long (16 h of light/24 h) or short (6 h of light/24 h) photoperiods. Following exposure to either photo-period for 11-12 weeks, a subset of the animals was fitted with an indwelling jugular cannula. Blood samples were taken hourly over a 24-h period and plasma levels of FSH were determined by RIA. Knife cuts placed ventral to or through the ventral portions of the PVN prevented short day-induced anestrus. On the day of proestrus, peak elevations of FSH in cycling animals with knife cuts in both photoperiods, as well as in sham-operated females in long days, occurred 4-5 h before lights out. In contrast, sham-operated anestrous females in short days showed peak elevations of FSH approximately 3-4 h after lights out. The present results support the view that neural connections between the SCN and the PVN mediate the effects of short days on reproductive physiology, including changes in the timing of the FSH surge. PMID- 1901508 TI - Hypokinesia, rigidity, and tremor induced by hypothalamic 6-OHDA lesions in the rat. AB - Bilateral administration of 6-hydroxydopamine in the medial fore-brain bundle at the level of the posterolateral hypothalamus in rats resulted in hypokinesia, muscular rigidity and tremor as determined by various behavioral assessment procedures. These neurological signs were accompanied by marked decreases in the concentrations of dopamine and its main metabolites dihydroxyphenylacetic acid and homovanillic acid in both striatum and nucleus accumbens. Administration of apomorphine (1 mg/kg) or L-Dopa (60 mg/kg) reversed or totally abolished the hypokinesia, rigidity and tremor in lesioned animals. Together, the present findings demonstrate that bilateral intrahypothalamic administration of 6-OHDA results in the appearance of the three cardinal symptoms of Parkinson's disease in rats. This model should prove to be valuable for both the study of the neuropathological processes underlying the neurological signs of this disease and the screening of potential antiparkinson agents. PMID- 1901509 TI - Waldenstrom's macroglobulinemia: long-term results with the M-2 protocol. AB - Thirty-three patients with symptomatic Waldenstrom's macroglobulinemia have been treated with the M-2 protocol (BCNU, cyclophosphamide, vincristine, melphalan, and prednisone). Therapy was administered every 5 weeks for 2 years and every 10 weeks for an additional 1-3 years. Median clinical and laboratory parameters included age 70 years (range 52-87), performance status 1 (1-3), prior therapy 7, weight loss 12, symptomatic hyperviscosity 13, splenomegaly 22, lymphadenopathy 7, hemoglobin 9.6 g/dl (6.7-14.6), IgM paraprotein level 2000 mg% (340-11,600), and serum viscosity 2.1 (1.4-6.0). Responses were observed in 27 patients, of whom 21 were partial responses. Survival ranges from 1 to 120+ months with 58% of patients projected to be alive at 10 years. Twenty-one patients remain alive, of whom 10 are greater than or equal to 6 years from initiation of therapy with M-2. Treatment has been well tolerated with usually only mild to moderate hematologic toxicity. Median nadir white blood cells during the first cycle was 3000/mm3 (1000-5500). Peripheral neuropathy was seen in 54% secondary to vincristine. Nausea/vomiting, anemia requiring transfusions, and alopecia were each noted in approximately 25% of patients. Sepsis was observed in 2 patients. Two characteristics, age and prior therapy, were found to be of borderline statistical significance (p = 0.03) using univariate analysis but were not significant with multivariate analysis. The M-2 protocol may be able to produce prolonged survival in the majority of patients with Waldenstrom's macroglobulinemia. Additional trials are needed to develop recommendations for therapy as well as factors predictive for survival and suitability for treatment. PMID- 1901510 TI - Waldenstrom's macroglobulinemia. PMID- 1901511 TI - Difference in label length between demethylchlortetracycline and oxytetracycline: implications for the interpretation of bone histomorphometric data. AB - We measured the individual lengths of fluorescent labels on the three subdivisions of the endosteal envelope in iliac bone biopsy specimens produced by the administration of both oxytetracycline and demethylchlortetracycline. Fifty one healthy subjects and 53 patients with postmenopausal osteoporosis were labeled in the stated order, and 8 osteopenic patients were labeled in the reverse order. Whatever the order of administration, the demethylchlortetracycline label was longer than the oxytetracycline label. We conclude: (1) the difference in label lengths reflects a difference between the two compounds in some intrinsic property, whether physical, chemical, or pharmacokinetic. (2) If the calculation of extent of mineralizing surface is based on the mean length of the two labels, a suitable correction should be applied to the shorter label; alternatively, the length of the longer label alone should be used. (3) Unlabeled osteoid not due to label escape probably results from slow terminal mineralization after cessation of matrix synthesis during which too few tetracycline molecules are incorporated to exceed the threshold for visible fluorescence, rather than from the temporary interruption of mineralization followed by its resumption. PMID- 1901513 TI - Effect of radiation on the expression of carcinoembryonic antigen of human gastric adenocarcinoma cells. AB - The changes of antigenic expression of cultured human gastric adenocarcinoma MKN45 cells caused by irradiation were investigated to elucidate the immune responses to localized irradiation. The expression of carcinoembryonic antigen (CEA) showed remarkable increases in the culture supernatant and on the surface of the membrane of irradiated cells. The expression of major histocompatibility complex Class I antigen on the membrane also was enhanced by irradiation. In addition, the irradiated cell groups, when analyzed using a CEA-specific probe, showed remarkable increases in the CEA mRNA. These enhancements increased in the 10-Gy and 15-Gy irradiated populations compared with the 5-Gy irradiated population. These results suggest that the enhancement of expression of CEA by radiation takes place at the CEA gene expression (mRNA) level but not at the protein level. PMID- 1901512 TI - X-ray microanalysis of ossified auricles in Addison's disease. AB - The element content of ossified auricles in two patients with Addison's disease was determined by X-ray microanalysis. The results showed a similar element content of the ossified auricles of the Addison's patients and control bone specimens. The calcium and phosphorus content of the petrified auricles was, however, slightly decreased compared with the iliac bone biopsies of the patients. The sulfur content of the ossified auricles was higher than that of their bones, but markedly lower than control auricular cartilage. Iron, sodium, and chloride contents were similar in the ossified auricles and in the normal auricular cartilage, whereas only trace amounts of these elements were detected in the bone. The auricles of the patients with Addison's disease possessed relatively high aluminium content compared with both control bone and cartilage. The element content of the bone biopsies from Addison patients was comparable to control bone. The presence of trace amounts of aluminium in the petrified auricles of Addison's patients is probably attributed to a long period of aluminium hydroxide consumption. PMID- 1901514 TI - Formation of neutralizing antibodies against natural interferon-beta, but not against recombinant interferon-gamma during adjuvant therapy for high-risk malignant melanoma patients. AB - In an adjuvant clinical trial, 34 high-risk malignant melanoma patients were treated with natural interferon (IFN)-beta and recombinant IFN-gamma. Patients with tumor location on head, neck, and trunk received 3 million IU IFN-beta intravenously (IV) three times weekly for 24 weeks. Patients with tumor location on the extremities received subcutaneous (SC) injection of 2 million IU of IFN beta distal the locoregional lymph nodes instead. All patients were given 50 micrograms IFN-gamma SC on 3 consecutive days every 4 weeks. Antibody formation was detected by coincubation of IFN and patients' serum and assessment of the inhibition of the cytopathic effect by a virus suspension. Soluble interleukin-2 receptors (sIL-2R) were determined by enzyme-linked immunosorbent assay (ELISA) technique. No antibodies against IFN-gamma were observed. The overall incidence of antibody formation to IFN-beta was 55.8% (19/34). Ninety-two percent of the SC treated patients (13/14) and 30% (six of 20) of the IV-treated patients developed antibodies. Soluble interleukin-2 receptors were found to be significantly lower in antibody-positive patients than in antibody-negative patients. The authors conclude that IFN-beta antibody formation is frequent and might influence IFN induced sIL-2R elevation in vivo. PMID- 1901515 TI - The acetylcholinesterase gene of Anopheles stephensi. AB - 1. The acetylcholinesterase (AChE) gene from the important malaria vector Anopheles stephensi has been isolated by homology to the Drosophila acetylcholinesterase gene. 2. The complete sequence and intron-exon organization has been determined. The encoded protein has 69% identity to Drosophila AChE and 38 and 36% identity to Torpedo AChE and human butyrylcholinesterase, respectively. PMID- 1901516 TI - Site-directed ribose methylation identifies 2'-OH groups in polyadenylation substrates critical for AAUAAA recognition and poly(A) addition. AB - The importance of sugar contacts for the sequence-specific recognition that occurs during polyadenylation of mRNAs was investigated with chemically synthesized substrates containing 2'-O-CH3 groups at selected riboses. An RNA (5' CUGCAAUAAACAAGU-UAA-3') with 2'-O-CH3 ribose at each nucleotide except for the AAUAAA sequence and 3'-terminal adenosine was efficiently polyadenylated in vitro. Methylation of single riboses within AAUAAA inhibited both poly(A) addition and binding of the specificity factor, but the magnitude of inhibition varied greatly at different nucleotides. Nucleotides that showed sensitivity to base substitutions did not necessarily show sensitivity to ribose methylation, and vice versa. The data indicate that the specificity factor interacts with AAUAAA through RNA-protein contacts involving essential recognition of both sugars and bases at different nucleotide positions. PMID- 1901517 TI - Integration of developmental signals and the initiation of sporulation in B. subtilis. PMID- 1901518 TI - Macrophage chemotactic factor partially purified from granulomatous inflammation. AB - Pathophysiological roles of macrophage chemotactic factor (MCF) in granulomatous inflammation were investigated. MCF was extracted in 10 mM phosphate-buffered saline, pH 7.4, from experimentally produced epithelioid cell granulomas in the liver and skin of mice. MCF activity reached a peak in the lesions prior to the time when granulomatous inflammation became maximal. MCF was then purified from 10-week-old hepatic granulomas and 2-week-old skin lesions by gel filtration, ion exchange column chromatography, and HPLC gel filtration. MCF from either liver or skin had a molecular weight about 650 kDa. MCF from hepatic granulomas was coupled to Affi-Gel beads and transplanted subcutaneously into naive mice. In vivo macrophage chemotaxis was observed around the beads and the cells formed a sheet, but organization of macrophages into granulomas did not occur with the MCF active fractions. Macrophage chemotaxis alone is insufficient to elicit granulomatous inflammation. PMID- 1901519 TI - Antigen presenting ability of thymic macrophages and epithelial cells: evidence for defects in the antigen processing function of thymic epithelial cells. AB - We compared the antigen presenting ability of cloned thymic macrophage and epithelial cell lines using T cell hybridomas with well-characterized activation requirements. A cloned thymic epithelial cell line (3D.1), preinduced with interferon-gamma (IFN-gamma) activated the T cell hybridoma 3DO-18.3 but not the T cell hybridoma DO-11.10. Analyses using preprocessed antigen suggest that the failure of 3D.1 to activate DO-11.10 is due to its inability to process chicken ovalbumin to produce a peptide recognized by the Ag:MHC T cell receptor of DO 11.10. The epithelial cell line 3D.1 was able to activate DO-11.10 if the superantigen staphylococcal enterotoxin B was used for activation instead of ovalbumin. These observations indicate that IFN-gamma-induced 3D.1 expresses sufficient I-Ad molecules to activate DO-11.10 but is unable to produce the peptide of ovalbumin recognized by DO-11.10. Furthermore, 3D.1 appears to be representative of nonmacrophage thymic stromal cells cultured in vitro, since heterogeneous cultures containing epithelial cells exhibited the same selective T cell activation characteristics. In contrast, thymic macrophage cell lines activated all T cells studied. These results suggest that there is a functional difference between the capacity of thymic epithelial cells and macrophages to process and present antigen to T cells. PMID- 1901520 TI - Regulation of macrophage activation markers by IL-4 and IFN-gamma is subpopulation-specific. AB - We have addressed the differential regulatory properties that IFN-gamma and IL-4 exert on macrophage (M phi) subpopulations. For this purpose, Thyoglicolate-, Peptone-, and Con A-elicited M phi, as well as bone marrow-derived M phi and P388D1 cells, were cultured in the presence of either IFN-gamma or IL-4. The expression of LFA-1, Mac-1, and Mac-2 after this treatment was studied by FACS analysis. We have found that these surface molecules are differentially modulated by the two lymphokines, depending on the M phi subpopulation studied. Mac-1 is upregulated only in Thyoglicolate-elicited cells after treatment with IFN-gamma, while no change in the expression of Mac-2 was observed in any of the groups. LFA 1 is upregulated by IFN-gamma in Thyoglicolate- and bone marrow-derived M phi and P388D1 cells, while IL-4 does not induce LFA-1 on these cells. Interestingly, however, we have observed the reverse situation on Con A-elicited M phi, where a strong induction of LFA-1 is achieved by treatment of the cells with IL-4, while IFN-gamma does not modify the expression of this antigen. Our results obtained with the lymphokine-stimulated M phi are interpreted in the context of functionally induced M phi subpopulations, which might be regulated by either Th1 or Th2 CD4+ T cells. Thyoglicolate-elicited M phi may represent the in vitro equivalent of a M phi subpopulation regulated in vivo by Th1 cells while Con A elicited M phi could be the equivalent of a subpopulation regulated by Th2 cells. PMID- 1901521 TI - Ability of cell-sized beads bearing tumor cell membrane proteins to stimulate LAK cells to secrete interferon-gamma and tumor necrosis factor-alpha. AB - We recently reported that lymphokine activated killer (LAK) cells were stimulated to release both interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF alpha) when stimulated by a variety of tumor cells. We proposed then that the released cytokines may play a role in mediating tumor cell regression in vivo. In this paper, we provide further information on the nature of the signals, provided by the tumor cells (K562 erythroleukemia), that stimulate LAK cells to secrete IFN-gamma and TNF-alpha. Using a previously published protocol for coating tumor membrane molecules onto cell-sized hydrophobic beads (also called pseudocytes), we demonstrate that the signal provided by the tumor cell is membrane associated. Beads coated with K562 membranes stimulated LAK cells to release IFN-gamma and TNF-alpha. The pretreatment of these beads with trypsin and sodium periodate eliminated the ability of these pseudocytes to stimulate cytokine release in LAK cells. The glycoproteins that stimulate LAK cells to secrete IFN-gamma and TNF alpha were further enriched by their ability to bind concanavalin A (Con A, Jack Bean). To determine if the tumor-associated molecules that stimulate LAK cells to release IFN-gamma and TNF-alpha are also the molecules involved in mediating tumor cell lysis, we tested the ability of the Con A binding and nonbinding proteins to inhibit the LAK cell-mediated lysis of K562 cells. Our results demonstrate that molecules that inhibited LAK cell-mediated cytotoxicity were not enriched by Con A. These results are therefore consistent with the conclusion that different sets of tumor-associated molecules are involved in the stimulation of LAK cells to secrete cytokine and in the induction of LAK cells to mediate tumor cell cytolysis. PMID- 1901523 TI - Resistant keratinocytes in 7,12-dimethylbenz[a]anthracene-initiated hamster buccal pouch epithelium. AB - In order to test the hypothesis that the property of resistance to cytotoxicity is an acquired trait of premalignant oral mucosal epithelium, cell dissociates were prepared from in vivo initiated hamster buccal pouch epithelium (HBPE), non initiated HBPE and malignant HBPE cell lines. These cell types were evaluated for resistance to the cytotoxic effects of the inducing carcinogen, 7,12 dimethylbenz[a]anthracene (DMBA). A mitoinhibition assay and a clonogenicity assay were used to assess the ability of these cells to replicate or form colonies in the presence of 40 microM DMBA. Replication of primary plated HBPE cells was inhibited by 100% in both assays. PO II, a cell line derived from non initiated, paraffin-oil-exposed HBPE, was inhibited by 97 and 100% in the mitoinhibition and colony-forming assays respectively. This same cell line, like primary plated HBPE, lacked the transformation-linked traits of angiogenesis and anchorage-independent growth. By contrast, three malignant HBPE cell lines, two derived during long-term culture of DMBA-initiated HBPE, and one from a DMBA induced HBPE carcinoma, were inhibited by only 34% or less in the assays for resistance to cytotoxicity. Primary cell cultures derived from HBPE initiated in vivo with twice-weekly topical applications of a 0.5% solution of DMBA in paraffin oil, for 3 or 5 weeks, were inhibited to an intermediate degree, indicating the presence of DMBA-resistant cells. In addition, DMBA-resistant cell colonies were observed in cell cultures prepared at 2, 6 and 10 weeks after completing the 5 week initiation regimen. Progenitors of the resistant cells, persisting in vivo for several weeks after initiation, may represent early preneoplastic cell populations in this experimental model. PMID- 1901522 TI - Beta-deuteration of N-nitrosoethylmethylamine causes a shift in DNA methylation from rat liver to esophagus. AB - While N-nitrosoethylmethylamine (NEMA) is carcinogenic primarily for the liver, its beta-trideuterated derivative, N-nitroso( [2-D3]ethyl)methylamine (NEMA-d3), also produces a high incidence of tumors in the esophagus. To determine whether this shift in organ specificity is associated with an altered pattern of DNA alkylation, [methyl-14C]- and [1-ethyl-14C]-labeled NEMA-d3 were administered to adult male Fischer 344 rats as a single i.p. dose (0.05 mmol/kg; 4 h survival). Levels of methylated and ethylated purines in the DNA of various organs were determined by radio-chromatography on Sephasorb-HP columns. When compared to previous data using undeuterated NEMA, 7-methylguanine levels were found to be reduced by approximately 30% in liver and kidney, but were 160% greater in esophagus. This resulted in a decrease in the 7-methylguanine ratio for liver/esophagus from 109 to 29. O6-Methylguanine was diminished in liver and kidney, but levels in lung and esophagus were too low for quantitative detection. Similarly, deuteration led to an 18% decrease of 7-ethylguanine in hepatic DNA. The observed increase in esophageal DNA methylation correlates with the increased carcinogenicity of NEMA-d3 relative to undeuterated NEMA in that organ. Since pharmacokinetic studies have shown that beta-trideuteration of NEMA does not alter its bioavailability, the data suggest that the observed shift in target organ results from isotopically-induced changes in the balance among competing metabolic pathways in different rat tissues. PMID- 1901524 TI - Facilitation of dimethylbenz[a]anthracene-induced rat mammary tumorigenesis by restraint stress: role of beta-endorphin, prolactin and naltrexone. AB - In order to investigate the involvement of opioid peptides and prolactin in stress-facilitated mammary cancer, we studied the effect of chronic restraint stress on dimethylbenz[a]-anthracene (DMBA)-induced mammary tumorigenesis and the effect of an opiate antagonist, naltrexone, on this process. Female Fischer-344 rats (n = 160) were administered 15 mg DMBA/ml of sesame oil/rat by intragastric intubation. Eighty rats were subjected to daily 30 min restraint stress in a plastic cylinder, and 80 rats served as control not subjected to the stressor. Half of the rats from each group received naltrexone (1 mg/kg, i.p. daily). Five rats from each group (restraint stress +/- naltrexone and control +/- naltrexone) were killed every 2-3 weeks. Rats subjected to restraint stress developed a greater number of tumors earlier. Naltrexone decreased the tumor incidence in the stressed animals from 32 to 12% (P less than 0.001) and in unstressed rats from 27 to 15% (P less than 0.001) at the end of 18 weeks. Stressed rats showed a decrease of 48% (P less than 0.001) in the level of hypothalamic beta-endorphin. Plasma prolactin increased from 4-13 ng/ml in the control rats to 109-396 ng/ml (P less than 0.001) in the stressed rats throughout the 18 week period. The beneficial effect of naltrexone was associated with 42% (P less than 0.01) increase in T cell proliferation, but greater than 90% (P less than 0.001) decrease in plasma prolactin level was observed in naltrexone-treated rats compared to the untreated animals. Rats subjected to restraint stress showed a 15% (P less than 0.001) decrease in weight gain at the end of the experiment (18 weeks). Neither restraint stress nor naltrexone administration affected the caloric intake of rats during this period. Thus, we believe that restraint stress facilitates DMBA-induced mammary tumors by releasing beta-endorphin and prolactin, and naltrexone shows a beneficial effect by opposing the effect of beta-endorphin on prolactin release in the stressed animals. PMID- 1901525 TI - Dinitropyrene nitroreductase activity of purified NAD(P)H-quinone oxidoreductase: role in rat liver cytosol and induction by Aroclor-1254 pretreatment. AB - Dinitropyrenes (DNP) are potent bacterial mutagens in the Ames test and genotoxins in cultured mammalian cells. Rat liver cytosol contains nitroreductases that are critical in the activation of DNP to the ultimate DNA binding species. In order to study the nature and inducibility of liver cytosolic enzymes involved in the activation of DNP, cytosolic nitroreductase activities towards three DNP isomers (1,3-, 1.6- and 1,8-DNP) were determined in Aroclor pretreated and untreated rats. Aroclor-1254 pretreatment resulted in up to 5-fold induction of cytosolic DNP nitroreductase. This induction was reflected in at least a 15-fold increase in cytosolic NAD(P)H-quinone oxidoreductase (NQOR) (E.C. 1.6.99.2) activity. The rates of nitroreduction for the three DNP isomers followed the order 1,6- greater than 1,8- greater than 1,3-DNP in all cases studied. 1,6-DNP nitroreductase coeluted with NQOR activity upon affinity purification. Highly purified NQOR catalyzed the NADH- and NADPH-dependent reduction of each of the three DNP isomers and displayed the same stereospecificity as the cytosolic activity. These results provide evidence that NQOR participates in the cytosolic nitroreduction of DNP and constitutes a major part of the total DNP nitroreductase activity upon induction of NQOR by Aroclor 1254 pretreatment. Thus, the role of NQOR in the metabolism of these mutagens depends significantly upon the degree to which this enzyme is induced. PMID- 1901526 TI - Immunological and HPLC detection of aflatoxin adducts in human tissues after an acute poisoning incident in S.E. Asia. AB - Acid hydrolysed, purified DNA, extracted from formalin fixed human tissues from persons acutely exposed to aflatoxins during a poisoning incident, was found to inhibit antibody binding in a competitive aflatoxin inhibition ELISA both before and after immunoaffinity column purification. HPLC analysis of acid hydrolysates of the DNA revealed a peak with a retention time 3 min earlier than 8,9-dihydro-2 (N7-guanyl)-9-hydroxy AFB1 synthesized either by peracid activation or direct reaction of the 8,9-oxide with DNA. The major peak seen when DNA was extracted from formalin fixed tissues from rats treated with aflatoxin B1 was identical to that seen in the formalin fixed human tissues. Adduct levels ranged from 0 to 170 x 10(6) nucleotides depending on tissue type and individual examined. PMID- 1901527 TI - Relations between heart rate, ischemia, and drug therapy during daily life in patients with coronary artery disease. AB - BACKGROUND: Previous studies have shown that little if any increase in heart rate occurs 1 minute before the onset of ischemia in ambulant patients with coronary artery disease. This study tested the hypothesis that there are characteristic relations between heart rate and ischemia in ambulant patients with coronary artery disease. METHODS AND RESULTS: Twenty-one patients with proven coronary disease demonstrated 212 episodes of ischemia during 504 hours of continuous monitoring of the electrocardiogram. An important increase in heart rate (from 74 +/- 11 to 90 +/- 14 beats/min, p less than 0.001) occurred between 5 and 30 minutes (not 1 minute) before the onset of ischemia. A significantly higher heart rate at onset of ischemia was seen during Bruce protocol exercise testing than during daily life (117 +/- 12 versus 95 +/- 15 beats/min, p less than 0.01). However, when a less-strenuous, but more prolonged, exercise protocol was used in a subgroup of patients (n = 12), ischemia occurred at a heart rate that was significantly lower than during the Bruce protocol (88 +/- 14 versus 103 +/- 15 beats/min, p less than 0.05) and was not significantly different from the threshold heart rate at onset of ischemia during daily life (88 +/- 14 versus 84 +/- 12 beats/min, p = NS). As part of two placebo-controlled trials, treatment with both propranolol and nitroglycerin altered the distribution of ischemic events by heart rate but in opposite directions. Although propranolol largely eliminated events occurring at high (greater than 100 beats/min) and moderate (80 100 beats/min) heart rates, the number of events at low (less than 80 beats/min) heart rates was increased. In contrast, nitroglycerin reduced episodes at low and moderate heart rates only. CONCLUSIONS: Important increases in heart rate occur before the onset of ischemia during daily life, but this increase occurs much earlier than has been reported. Duration of heart rate increase appears to influence the heart rate threshold for ischemia, and this may contribute to the occurrence of ischemia at lower heart rates during daily life than during standard exercise testing. Last, different classes of drugs appear to have characteristic effects on ischemia occurring at different heart rates that may be useful in planning therapy. PMID- 1901528 TI - Prevention of nitrate tolerance with angiotension converting enzyme inhibitors. AB - BACKGROUND: Activation of neurohumoral hormones or sulfhydryl group depletion may contribute to the development of nitroglycerin tolerance. In an attempt to prevent nitrate tolerance, this study evaluated the interaction of nitroglycerin with angiotensin converting enzyme (ACE) inhibitors with and without a sulfhydryl group. METHODS AND RESULTS: Thirty-four subjects were randomized to a 7-day regimen of enalapril 10 mg b.i.d., captopril 25 mg t.i.d., or placebo. Venodilator response to nitroglycerin was assessed with forearm plethysmography by measuring the change in venous volume after administration of 0.4 mg sublingual nitroglycerin. Plethysmographic measurements were obtained serially 1) at baseline, 2) after 4 days of ACE inhibitor or placebo, 3) 2 hours after application of a 10 mg/24 hr nitroglycerin patch, and 4) 74 hours after continuous nitropatch application. ACE inhibition alone caused no significant change in the response to sublingual nitroglycerin. Nitrate response remained unchanged after 2 hours ("acute") of nitropatch exposure in all three groups. After 74 hours ("chronic") of continuous nitropatch application, the venodilator response to sublingual nitroglycerin was reduced by 40% in the placebo group, 10% in the enalapril group, and 2% in the captopril group. This attenuation was significant only in the placebo group (p less than 0.01). Pairwise comparison of nitrate response between groups was significantly different between the captopril and placebo groups (p less than 0.01) and between the placebo and enalapril groups (p less than 0.05). Plasma renin levels increased equally in the enalapril and captopril groups. Body weight increased only in the placebo group, suggesting prevention of nitrate-induced volume expansion in the ACE inhibitor groups. CONCLUSIONS: This study demonstrates that ACE inhibitors may prevent nitrate tolerance to long-term nitrate therapy. PMID- 1901529 TI - Significance of a negative exercise thallium test in the presence of a critical residual stenosis after thrombolysis for acute myocardial infarction. AB - BACKGROUND: After thrombolytic therapy for acute myocardial infarction, increasing emphasis is placed on early submaximal exercise testing, with further intervention advocated only for demonstrable ischemia. Although significant residual coronary artery lesions after successful thrombolysis are common, many patients paradoxically have no corresponding provokable ischemia. METHODS AND RESULTS: The relation between significant postthrombolytic residual coronary artery disease and a negative early, submaximal exercise thallium-201 tomogram was studied among 101 consecutive patients with uncomplicated myocardial infarction and at least 70% residual stenosis of the infarct artery. A negative test occurred in 49 (48.5%) patients with a mean 88% residual infarct artery stenosis. Further characteristics of the group were as follows: mean time to treatment was 3.1 hours; mean age was 54 +/- 10 years; 80% were male; 47% had anterior infarction; 39% had multivessel disease; mean left ventricular ejection fraction was 53 +/- 14%; and mean peak creatine kinase level was 3,820 +/- 3,123 IU/ml. A similar group of 52 (51.5%) patients, treated within 3.3 hours from symptom onset, with a mean postthrombolysis stenosis of 90%, had a positive exercise test. Characteristics of this group were as follows: age was 58 +/- 10 years; 92% were male; 56% had anterior infarction; 40% had multivessel disease; and mean left ventricular ejection fraction was 54 +/- 15%. The peak creatine kinase level associated with the infarction, however, was lower: 2,605 +/- 1,805 IU/ml (p = 0.04). There was no difference in performance at exercise testing with respect to peak systolic pressure, peak heart rate, or time tolerated on the treadmill between the two groups. By multivariate logistic regression, only peak creatine kinase level predicted a negative stress result in the presence of a significant residual stenosis (odds ratio, 4.2; 95% confidence interval, 1.1 16.3). CONCLUSIONS: The explanation for the relatively frequent finding of a negative early stress 201Tl tomogram after apparently successful reperfusion appears to be more extensive myocardial necrosis and not delay in therapy or inadequate exercise performance. PMID- 1901530 TI - A1-adenosine receptor inhibition of adenylate cyclase in failing and nonfailing human ventricular myocardium. AB - BACKGROUND: Receptors that couple via the stimulatory G protein, Gs, to adenylate cyclase and to a positive inotropic response have been extensively investigated in falling human heart. In contrast, much less is known about receptors, such as the A1-adenosine receptor, that couple to adenylate cyclase via the inhibitory G protein, Gi, to give a negative inotropic response. Activation of such Gi-coupled receptors might worsen heart failure. Furthermore, alpha Gi is increased in failing human ventricular myocardium, which may enhance inhibitory receptor coupling to adenylate cyclase. METHODS AND RESULTS: A1-Adenosine receptor inhibition of adenylate cyclase was examined in crude particulate preparations derived from 12 nonfailing and 12 failing human left ventricles. Experimental conditions were designed for maximal inhibitory responses. Dose-response curves were performed with the selective A1-adenosine receptor agonist R-phenylisopropyl adenosine (R-PIA). No differences in nonfailing versus failing heart were observed for basal adenylate cyclase activity (49.0 +/- 4.1 versus 45.7 +/- 2.6 pmol cyclic AMP/min/mg), maximal R-PIA-mediated inhibition (31.1 +/- 2.6 versus 30.2 +/- 1.6 pmol cyclic AMP/min/mg), ED50 (R-PIA x 10(-7) 1.28 +/- 0.10 versus 1.36 +/- 0.08), or slope (1.06 +/- 0.06 versus 1.03 +/- 0.10), respectively. Furthermore, fluoride, forskolin, and manganese adenylate cyclase activation were not different in failing heart, which is consistent with no change in the catalytic unit of adenylate cyclase. The inhibitory G protein alpha Gi, as quantitated by pertussis toxin-catalyzed ADP-ribosylation, was increased in failing heart (105.7 +/- 5.8 versus 132.7 +/- 3.4 optical density units, p less than 0.003). Basal adenylate cyclase activity was reduced in failing heart (7.8 +/- 0.8 versus 4.5 +/- 0.4 pmol cyclic AMP/min/mg, p less than 0.005) with assay conditions designed to assess G protein effects. CONCLUSIONS: The A1-adenosine receptor pathway exerts a major inhibitory effect on human myocardial adenylate cyclase activity. Although alpha Gi was increased in failing heart, A1-adenosine receptor inhibition of adenylate cyclase was not altered in preparations of failing versus nonfailing human ventricular myocardium. PMID- 1901532 TI - Resource management and imaging departments. PMID- 1901531 TI - Induction of sustained patency after clot-selective coronary thrombolysis with Hybrid-B, a genetically engineered plasminogen activator with a prolonged biological half-life. AB - BACKGROUND: Despite the utility of tissue-type plasminogen activator (t-PA) in eliciting coronary thrombolysis clinically, early reocclusion remains a problem, occurring despite anticoagulation in 5-30% of patients with initially successful recanalization. This study evaluated the utility of Hybrid-B, a molecular variant of t-PA with a prolonged half-life in the circulation, in eliciting coronary thrombolysis and maintaining patency in the presence of a continuing thrombogenic stimulus. METHODS AND RESULTS: In intact, anesthetized dogs, either 18 mg Hybrid B over 30 minutes (n = 15) or 50 mg t-PA (Activase) over 60 minutes (n = 8) was administered starting 60 minutes after left anterior descending coronary artery occlusion was induced with a thrombogenic copper coil. Time to lysis averaged 54 +/- 26 (means +/- SD) minutes and 64 +/- 34 minutes with Hybrid-B and t-PA, respectively (p = NS). When Hybrid-B was administered as a bolus (20 mg over 1 minute) to induce a high initial concentration in blood, time to lysis was shortened markedly and averaged 15 +/- 5 minutes. Dogs given Hybrid-B by either infusion or bolus exhibited prolonged time to reocclusion (337 +/- 192 minutes compared with 192 +/- 125 minutes in dogs given t-PA, p less than 0.03), reflecting maintenance of a subthrombolytic but persistently active concentration of activator in blood. Despite the persistence of Hybrid-B in blood, concentrations of fibrinogen and alpha 2-antiplasmin were not depleted markedly and remained at 77 +/- 25 and 56 +/- 24%, respectively, of control values. CONCLUSIONS: Thus, Hybrid-B, a novel variant of t-PA with unique pharmacokinetic properties, elicits prompt, sustained, and clot-selective coronary thrombolysis. PMID- 1901533 TI - The role of ultrasound in the early diagnosis and management of heterotopic bone formation. AB - Heterotopic bone formation (HBF) is one of the many causes of painful limb swelling and is well recognized as posing clinical, radiological, and pathological diagnostic difficulties. We have evaluated the use of sonography to determine its role in reaching a diagnosis at a time when symptoms are maximal and the radiological diagnostic features absent. Serial ultrasound examination identified unique 'zone phenomea' in a heterogeneous group of eight patients before the classic radiological features appeared. The zone transformation matches the evolution and maturation process described pathologically and forms the basis of an early definitive diagnosis in all cases. The sonographic features are specific for the condition, unlike the scintigraphic appearances. Although CT confirms the peripheral location of the calcification, the low cost, safety, and general availability of ultrasound scanning make it the optimum imaging method for diagnosing and monitoring heterotopic bone formation. PMID- 1901534 TI - Fleroxacin combined with rifampin. AB - We determined the effect of the combination of rifampin and fleroxacin against Enterobacteriaceae and streptococcal species. None of the 65 isolates tested by checkerboard assay demonstrated synergy, 12% of isolates showed an additive effect; 86.7% were indifferent, and only 1 isolate showed antagonism. The mean FIC was 1.2. When using 2 and 8 micrograms/ml of rifampin, fleroxacin MICs of 285 isolates of Enterobacteriaceae, Pseudomonas aeruginosa, Haemophilus influenzae, staphylococci, streptococci, Bacteroides, and Clostridium were not increased, but synergy was not demonstrated. Time-kill studies against Escherichia coli, P. aeruginosa, Enterobacter cloacae, Staphylococcus aureus, and Enterococcus faecalis failed to show increased killing when the two agents were present at one half the MBC. The fleroxacin-rifampin interaction is one of indifference but provides coverage for species not adequately inhibited by fleroxacin. PMID- 1901535 TI - Comparative antimicrobial activity of ceftibuten against multiply-resistant microorganisms from Belgium. AB - To study the activity of ceftibuten, we obtained multiply-resistant isolates from approximately 20 hospitals in Belgium. Against Enterobacteriaceae, all of the tested comparative compounds were more active than cefaclor, and ceftibuten and tigemonam were the most active of the agents tested. Ceftibuten MIC50s were less than or equal to 1 microgram/ml for most enteric bacilli species and 85% of strains were susceptible (less than or equal to 8 micrograms/ml). This level of activity compared favorably to that recorded for cefaclor (less than or equal to 8 micrograms/ml), cefetamet (less than or equal to 4 micrograms/ml), and cefteram (less than or equal to 1 microgram/ml), that is, 37%, 69%, and 59%, respectively. Ceftibuten, cefetamet, cefteram, and tigemonam were highly active against isolates of Haemophilus influenzae and Neisseria gonorrhoeae. None of the comparative agents were as active as cefaclor against staphylococcal isolates. Against streptococci, cefteram was the most active, and tigemonam the least active of the agents. The MIC90s of ceftibuten for strains of Streptococcus pneumoniae and Streptococcus pyogenes were 2 micrograms/ml and 0.5 microgram/ml, respectively. Strains of Streptococcus agalactiae were resistant to both ceftibuten and tigemonam; cefaclor and cefteram inhibited 100% of isolates of this species. Strains of Enterococcus faecalis and Pseudomonas aeruginosa were consistently resistant to all of the compounds. Overall, ceftibuten exhibited potent activity against many multiply-resistant clinical isolates. PMID- 1901537 TI - Endocrine changes in sows exposed to elevated ambient temperature during lactation. AB - Seven sows were placed into one of two environmental chambers at 22 C, 5 d prior to farrowing. On day 9 of lactation, one chamber was changed to 30 C (n = 4) and the other remained at 22 C (n = 3). On days 24 and 25, blood samples were collected every 15 min for 9 hr and 7 hr, respectively. On day 24, thyrotropin releasing hormone (TRH) and gonadotropin releasing hormone (GnRH) were injected iv at hour 8. On day 25 naloxone (NAL) was administered iv at hour 4 followed 2 hr later by iv injection of TRH and GnRH. Milk yield and litter weights were similar but backfat thickness (BF) was greater in 22 C sows (P less than .05) compared to 30 C sows. Luteinizing hormone (LH) pulse frequency was greater (P less than .003) and LH pulse amplitude was less (P less than .03) in 22 C sows. LH concentrations after GnRH were similar on day 24 but on day 25, LH concentrations after GnRH were greater (P less than .05) for 30 C sows. Prolactin (PRL) concentrations were similar on days 24 and 25 for both groups. However, PRL response to TRH was greater (P less than .05) on both days 24 and 25 in 30 C sows. Growth hormone (GH) concentrations, and the GH response to TRH, were greater (P less than .0001) in 30 C sows. Cortisol concentrations, and the response to NAL, were less (P less than .03) in 30 C sows. NAL failed to alter LH secretion but decreased (P less than .05) PRL secretion in both groups of sows. However, GH response to NAL was greater (P less than .05) in 30 C sows. Therefore, sows exposed to elevated ambient temperature during lactation exhibited altered endocrine function. PMID- 1901536 TI - In vitro activity of ceftibuten against Haemophilus influenzae and Branhamella catarhallis. AB - The in vitro activity of ceftibuten, a new orally administered cephalosporin, was assessed against clinical isolates of Haemophilus influenzae and Branhamella catarrhalis. The activity of ceftibuten was compared to that of ampicillin, amoxicillin-clavulanic acid, and three oral cephalosporins, cefaclor, cefuroxime, and cefixime. With the exception of rare beta-lactamase-negative ampicillin resistant strains of H. influenzae, resistance to ceftibuten was not observed with any of the study isolates. Ceftibuten was more active than amoxicillin/clavulanic acid for beta-lactamase-positive and -negative strains of H. influenzae; it was less active than this combination for B. catarrhalis. Ceftibuten was essentially equivalent in activity to cefixime against both Haemophilus and Branhamella but more active than cefaclor and cefuroxime against these two organisms. PMID- 1901538 TI - Effects of charcoal-extracted follicular fluid on reproductive function in postpartum cows. AB - In order to determine the role of follicle-stimulating hormone (FSH) on the resumption of ovarian function in cows early postpartum (PP), bovine follicular fluid (FF) was used to selectively suppress concentrations of FSH. Calves were removed from all cows within 24 hr of birth. Follicular fluid that was treated with charcoal to remove steroids (15 ml; n = 14) or serum (S) from an ovariectomized cow (15 ml, n = 14) was injected i.m. twice daily from days 1 to 10 PP. Blood samples were collected before each injection and frequent samples (every 15 min for 6 hr) taken on days 5 and 10 PP. Eight cows from each group (FF and S) were slaughtered on the morning of day 11 PP and pituitaries and ovaries collected. The remaining cows (n = 6) were observed for estrus. Treatment with FF delayed follicular growth (P less than 0.01), as evidenced by the largest follicle per cow observed at time of slaughter (3.6 +/- 0.42 vs 11.5 +/- 1.77 mm dia; FF vs S). The intervals from parturition to first estrus (P less than 0.11) and to first progesterone rise (25.3 +/- 1.97 vs 18.0 +/- 3.62 d; P less than 0.06) tended to be delayed by treatment with FF vs S. Many of the cows treated with S ovulated by day 10 PP, they were divided retrospectively into those that had ovulated by (n = 9) or after (n = 5) day 10 PP for analysis. Cows treated with FF had lower (P less than 0.05) and less variable (P less than 0.01) serum FSH concentrations while levels of luteinizing hormone (LH) tended (P less than 0.08) to be greater on days 5 and 10 PP. Follicular fluid decreased levels of FSH (P less than 0.001), but not LH (P less than 0.15), in the samples obtained twice daily compared to S-treated cows that did not ovulate by day 10 PP. Anterior pituitaries were dissociated, and cells from each cow were cultured in order to ascertain whether treatment with FF in vivo would affect gonadotropin secretion in vitro. Estradiol-17 beta (E) was incubated with pituitary cells to determine the effect of E on gonadotropin secretion from cells of PP cows, and to ascertain whether treatment with FF in vivo and with E in vitro would interact to affect secretion of FSH and LH in culture. After 2 d of incubation, cells were treated with 10(-9) M E or vehicle (1% ethanol).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1901539 TI - Effects of dopamine, norepinephrine and serotonin on secretion of luteinizing hormone, follicle-stimulating hormone and prolactin in ovariectomized, pituitary stalk-transected ewes. AB - Two experiments were conducted in ovariectomized, pituitary stalk-transected ewes to determine if dopamine (DA), norepinephrine (NE) or serotonin (5-HT) alter secretion of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and prolactin (PRL). In experiment 1, ewes were infused (iv) with saline (control), DA (66 micrograms/kg/min), NE (6.6 micrograms/kg/min) or 5-HT (6.6 micrograms/kg/min). Treatments did not alter pulse frequency, but 5-HT increased (P less than .05) amplitude of pulses of LH and mean concentrations of LH, DA and NE were without effect on basal secretion of LH. DA but not NE or 5-HT decreased (P less than .05) the release of LH in response to gonadotropin hormone-releasing hormone (GnRH, 25 micrograms, im). Concentrations of FSH were not affected by treatments. Secretion of PRL was reduced (P less than .05) by treatment with DA and NE but not 5-HT. Each amine reduced (P less than .05) the release of PRL in response to thyrotropin-releasing hormone (TRH; 3 micrograms, im). In experiment 2, ewes were given DA at doses of 0, 0.66, 6.6 or 66.0 micrograms/kg/min, iv. No dose altered basal LH, but each dose reduced (P less than .05) basal and TRH induced release of PRL. Key findings from these studies include direct pituitary action for: (1) 5-HT enhanced basal secretion of LH, (2) suppression of GnRH induced secretion of LH by DA. (3) DA and NE inhibition of PRL secretion, and (4) DA, NE and 5-HT inhibition of release of PRL in response to TRH. PMID- 1901540 TI - Effect of long-term administration of human growth hormone-releasing factor and (or) thyrotropin-releasing factor on hormone concentrations in lactating dairy cows. AB - Fifteen cows (87 +/- 8 d in lactation; 641 +/- 33 kg BW) were randomly assigned to treatment and then subjected for 182 d to daily sc injection (1000 hr), in the cervical area, of saline (control), thyrotropin-releasing factor (TRF: 1 micrograms/kg BW), growth hormone-releasing factor (1-29)NH2 (GRF; 10 micrograms/kg BW) or GRF plus TRF (10 and 1 micrograms/kg BW, respectively) according to a 2 x 2 factorial design. On days 1, 31, 88 and 179, jugular blood samples were collected from 2 hr before to 6 hr after injection. Samples were also collected for 5 consecutive days after cessation of treatment. GRF always induced growth hormone (GH) release (600 vs 7925 ng.min/ml) with augmentation of response with time (interaction GRF * day; P less than .001). TRF did not affect (P greater than .25) GH release; there was no interaction (P greater than .25) with time. There was no significant interaction (P greater than .25) between GRF and TRF on GH release. However, the amount of GH release with GRF plus TRF was always greater than with GRF alone (9419 vs 6431 ng.min/ml). TRF induced a significant release of prolactin (23769 vs 42175 ng.min/ml) but GRF reduced the amount of prolactin release on the last day of sampling. TRF induced thyroid stimulating hormone (TSH) release only on the first day of injection while triiodothyronine (T3) and thyroxine (T4) continued to respond to TRF throughout the treatment period. Concentrations of T3 and T4 fell below control levels after cessation of TRF injection. In conclusion, GRF-induced GH release and TRF-induced Prl and thyroid hormone release were maintained over a 6-mo treatment period. TRF induced TSH release only on the first day of injection. Overall, these results raised the possibility of a direct effect of TRF on the thyroid gland. PMID- 1901541 TI - Sequence of the CH1 and hinge-CH2 exons of the human immunoglobulin IGHA2 A2m(2) allele: comparison with the nonallelic and allelic IGHA genes. PMID- 1901542 TI - Characterization of a B-lymphocyte t(2;14) (p11;q32) translocation from an ataxia telangiectasia patient conferring a proliferative advantage on cells in vitro. AB - Patients with the recessively inherited disorder ataxia telangiectasia (AT) are particularly prone to the development of both B-cell and T-cell tumours. Specific translocations involving T-cell gene rearrangements and an unknown locus 3' of IGH have been described in AT T-cell clone and tumour cells. We describe here a t(2;14)(p11;q32) translocation which was observed in nonmalignant short-term cultured B lymphocytes from an AT patient. In vivo, the clone of cells grew from 1% to 6% of the total cell population over a period of 2 yr. Clonal translocations may therefore be associated with AT B cells, as well as AT T cells. B lymphocytes were transformed with Epstein-Barr virus, and the t(2;14) translocation cell was cellularly cloned. Using Southern filter analysis and in situ hybridisation to define more clearly the positions of the breakpoints, we show that the translocation at 14q32 involves a deletion within the IGH chain gene of at least J1, J2, DQ52, and sequences 1.5 kb 5' of DQ52 and that the breakpoint is either adjacent to the non-deleted JH sequences or upstream of these sequences, within the D or V regions, but proximal to all members of the VHII family of genes. The breakpoint at 2p11 is outside and proximal to IGK with respect to the centromere in an unknown gene. Sub-lines with an initially low proportion of translocation cells eventually became monoclonal in vitro for these cells. This suggests they have a growth advantage in vitro. PMID- 1901543 TI - Antibiotic concentrations in liquor compared to the minimal inhibitory concentrations of isolates in paediatric bacterial meningitis. The Finnish Study Group. AB - The susceptibilities of 171 bacteria which caused meningitis in 200 children were tested for their susceptibility as minimal inhibitory concentrations (MICs) for the antibiotics used in therapy. These antibiotics were chloramphenicol, ampicillin, cefotaxime and ceftriaxone. The MICs were compared to the minimal concentrations of the drugs seen in the cerebrospinal fluid (CSF) samples. The minimal bacteriostatic capacity (lowest concentration in CSF/MIC) of both cephalosporins was superior to that of chloramphenicol and ampicillin. The correlation of the finding with the speed of liquor sterilization in the treatment groups is discussed. PMID- 1901545 TI - Observation of a stable intermediate form in the reaction of human hemoglobin with carbon monoxide. AB - The reaction of human hemoglobin with carbon monoxide has been investigated near the equilibrium isosbestic wavelength (i.e. 426 nm). As previously reported by others [Gray, R.D. & Gibson, Q. H. (1971) J. Biol. Chem. 246, 5176-5178], in the presence of 0.1 M phosphate pH 7.0 a rise-and-fall kinetic pattern can be observed at this wavelength, which indicates the presence of at least one spectroscopically detectable intermediate species. In this paper we demonstrate that (a) the intermediate species is thermodynamically stable; (b) both phases refer to bimolecular processes; (c) only the initial fast phase is observed when deoxyhemoglobin is reacted with substoichiometric amounts of CO (i.e. final [CO]/[heme] less than or equal to 0.5); (d) only the second slow phase is observed when hemoglobin that is partially saturated with CO (Y less than or equal to 0.5) is reacted with saturating CO concentrations; (e) the CO dissociation rate constant measured on the intermediate formed after a partial CO saturation at a final Y approximately 0.4 has a value similar to that observed starting from the fully liganded form. These results can be accounted for by a two-state allosteric model [Monod, J., Wyman, J. & Changeux, J.-P. (1965) J. Mol. Biol. 12, 88-118] under the assumption that either (a) 426 nm is an isosbestic wavelength for the T0-R spectral changes but not for the T0-T liganded reaction; or (b) a functional heterogeneity of the two types of subunits is present in the T state and at this wavelength this feature is spectroscopically detectable. PMID- 1901544 TI - Effect of preincubation of Pseudomonas aeruginosa in subinhibitory concentrations of amikacin, ceftazidime and ciprofloxacin on adherence to plastic catheters. AB - The effect of preincubation of Pseudomonas aeruginosa in subinhibitory concentrations (1/4 x minimum inhibitory concentration) of amikacin, ceftazidime and ciprofloxacin on the expression of surface hydrophobicity and adherence to polyvinyl chloride, siliconized latex and polyurethane was evaluated. None of the antimicrobials significantly altered the expression of surface hydrophobicity. Subinhibitory concentrations of amikacin did not significantly reduce the adherence of P. aeruginosa to any of these 3 biomaterials. A significant inhibition of the adherence of polyvinyl chloride and siliconized latex but not to polyurethane was induced by both ceftazidime (p less than 0.05 to p less than 0.01 in different times) and ciprofloxacin (p less than 0.01). The effect of ceftazidime was present only for the first 4 h of bacteria-biomaterial interaction, whereas that of ciprofloxacin persisted throughout the study period (72 h). PMID- 1901547 TI - Long-term low-protein diet reduces the number of hippocampal mossy fiber synapses. AB - Previously we have reported a loss of the dentate granule cells and hippocampal CA3 pyramidal cells in adult animals after lengthy periods of low-protein diet. In this study we examined the effects of this cell loss upon the synaptic connections between the granule cell axons (the mossy fibers) and CA3 pyramidal cell dendrites. Three groups of five rats each were given a low-casein (8%) diet for 6, 12, and 18 months, respectively, and the results of the ultrastructural morphometric analysis compared with similarly processed control rats kept on a control diet. The numerical density of synapses was decreased in undernourished rats and the fraction of the mossy fiber terminal membrane occupied by synaptic specializations was reduced. It can be inferred that the synaptic connectivity pattern between mossy fiber terminals and CA3 dendrites is altered due to a reduction in the number of contacts. Besides, as the synapses of low-protein treated animals do not display any increase in the length of their active zones, evidence is not provided for the existence of morphological synaptic plasticity, contrary to what has been recently described in other experimental circumstances. PMID- 1901546 TI - Activation of signal-transducing guanine-nucleotide-binding regulatory proteins by guanosine 5'-[gamma-thio]triphosphate. Information transfer by intermediately thiophosphorylated beta gamma subunits. AB - Signal-transducing guanine-nucleotide-binding regulatory proteins (G proteins) are heterotrimers, composed of the nucleotide-binding alpha subunit and a beta gamma dimer. The influence of beta gamma dimer preparations of the retinal G protein transducin (TD) was studied on formylpeptide-receptor--G-protein interactions in membranes of differentiated HL 60 cells. For this, TD was prepared from bovine rod outer segment (ROS) membranes with either GTP or its analogs, guanosine 5'-[gamma-thio]triphosphate (GTP[S]) and guanosine 5'-[beta gamma-imino]triphosphate (Gpp[NH]p). After removal of free nucleotides, TD beta gamma was separated from TD alpha and its function analyzed. Addition of TD beta gamma isolated from TD prepared with GTP[S] (TD beta gamma GTP[S]) to HL 60 membranes abolished high-affinity binding of fMet-Leu-[3H]Phe (fMet, N formylmethionine) to its receptor. In contrast, TD beta gamma isolated from TD prepared with GTP (TD beta gamma GTP), boiled TD beta gamma GTP[S] and TD alpha prepared with GTP[S] had no or only slight effects. The inhibitory effect of TD beta gamma GTP[S] on fMet-Leu-[3H]Phe receptor binding was potentiated by GDP at low concentrations but not by GTP[S]. Furthermore, TD beta gamma GTP[S], but not TD beta gamma GTP or TD beta gamma isolated from TD prepared with Gpp[NH]p (TD beta gamma Gpp[NH]p), prevented fMet-Leu-Phe-stimulated binding of [35S]GTP[S] to G proteins in HL 60 membranes, measured in the presence of GDP. When TD beta gamma GTP was incubated with GTP [S] and TD-depleted illuminated ROS membranes, and subsequently separated from the membranes and free GTP[S], this TD beta gamma GTP, similar to TD beta gamma GTP[S], abolished high-affinity binding of fMet-Leu [3H]Phe to its receptor, fMet-Leu-Phe-stimulated binding of [35S]GTP[S], and fMet Leu-Phe-stimulated GTP hydrolysis in HL 60 membranes. Inhibition of [35S]GTP[S] binding by TD beta gamma was not seen in the presence of the metabolically stable GDP analog, guanosine 5'-[beta-thio]diphosphate. In order to obtain an insight into the modification of TD beta gamma apparently caused by GTP[S], and into its mechanism of action in HL 60 membranes, TD, TD alpha and TD beta gamma, all prepared in the presence of GTP, were incubated with [35S]GTP[S] and TD-depleted illuminated ROS membranes. Fluorographic analysis of the supernatant proteins revealed 35S labelling of the beta band of the G protein. When apparently thiophosphorylated TD beta gamma was incubated with [3H]GDP in the presence of HL 60 membranes, [3H]GTP[S] was rapidly formed.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1901548 TI - Downregulation of protein kinase C-gamma is independent of a functional kinase domain. AB - Prolonged activation of protein kinase C (PKC) types alpha and beta by tumor promoting phorbol esters leads to desensitization of the phorbol ester response, downregulation of protein kinase C activity and depletion of the protein kinase C polypeptide. When the gamma isoenzyme of PKC is transiently expressed in COS-1 cells and exposed to phorbol esters, PKC-Gamma is downregulated in COS cells although these cells do not normally express this subtype. A point mutation in the putative ATP-binding site (Lys-380----Met-380) of the protein kinase C gamma isoenzyme which results in a kinase-deficient enzyme does not interfere with this downregulation. Our results suggest that autophosphorylation or constitutive signalling through the protein kinase C-gamma kinase domain is not a prerequisite for downregulation of PKC activity. PMID- 1901550 TI - The assessment of bioavailable androgen levels from the serum free testosterone level. AB - Recently, it has been concluded that measurement of the serum free testosterone level is crucial for evaluating male gonadal function. However, the extent of the decline of serum free testosterone levels with aging and the actual levels in male infertility have not yet been clearly defined. In this study, the clinical significance of serum free testosterone levels was evaluated in a total of 248 subjects, including 120 healthy adult males (54 males aged 20-39, 26 males aged 40-59 and 41 males aged more than 60), 94 infertile males, 28 male hemodialysis patients, and 6 patients with Klinefelter's syndrome. Since the serum free testosterone levels correlate significantly with serum LH and FSH levels among 120 normal adult males, it appears that free testosterone has a biological action on the organ. In the subjects aged over 60, serum free testosterone levels were significantly decreased compared with the decrease of serum total testosterone. Thus, biologically active androgen levels decreased with aging. Serum free testosterone levels tended to decrease significantly from 40 years onwards. In infertile males, serum total testosterone levels were equal to those in normal adult males, but their serum free testosterone levels were significantly lower. This decrease of serum free testosterone may be one of the causes of their hypospermatogenesis. In male hemodialysis patients, serum total and free testosterone levels were not lower than in normal adult males. It is considered that the decline of percentage of serum free testosterone levels in aged males and infertile males was caused by increased serum sex hormone binding globulin (SHBG) levels. Several workers have shown that the production of SHBG is regulated by sex steroid hormones. In this study, however, serum SHBG levels were not correlated with the E2/T ratio. We concluded that measurement of the serum free testosterone level is of value in the endocrinological evaluation of male gonadal function. PMID- 1901549 TI - Actin depolymerization in the cyclic AMP-stimulated toad bladder epithelial cell, determined by the DNAse method. AB - Previous studies with the rhodamine phalloidin binding assay have shown that antidiuretic hormone and 8-Br-cAMP rapidly depolymerize F-actin in toad bladder epithelial cells. We have extended these studies with the DNAse inhibition assay and have found that in isolated epithelial cell suspensions, G-actin increases from 37 to 56% of total actin following 8-br-cAMP stimulation. The G-actin concentration in the epithelial cell greatly exceeds its critical concentration, indicating the requirement for a G-actin sequestering protein or proteins in this system. PMID- 1901551 TI - Cyclosporine A (CyA)-induced decrease of serum gonadotropin levels in a case of Klinefelter's syndrome. AB - We report a case of Klinefelter's syndrome who developed a decrease of serum gonadotropin levels, particularly LH, after CyA treatment for complicated focal glomerulosclerosis (FGS). A 38-year-old man suffering from general malaise and pretibial edema was diagnosed FGS by renal biopsy in October 1988, and was referred to our hospital for further evaluation and treatment for FGS in December 1988. He was not married, and closer anamnesis revealed that he had had impaired seminal ejaculation from the age of 30. The physical examination showed 37% obesity, scanty body hair, pretibial edema and small bilateral testes (3.0 x 1.5cm). Laboratory findings included marked proteinuria (5.3g/day) and mild renal dysfunction (serum creatinine 1.3mg/dl, glomerular filtration rate 57.2ml/min). Endocrinologically, high basal levels of LH and FSH (133.6mIU/ml and 93.7mIU/ml, respectively) and the hyperresponses of LH and FSH to LH-RH stimulation were found, but the other pituitary hormone levels, thyroid and adrenal status, were in the normal range. In testicular biopsy, nodularly proliferated Leydig cells and no seminal tubules could be seen. The chromosome analysis showed 47,XXY karyotype, which confirmed the diagnosis of Klinefelter's syndrome in this patient. From 9 January 1989, CyA (6mg/Kg.day) was orally administered for 4 weeks in order to treat for FGS. After CyA administration, basal levels of LH and FSH remarkably decreased, particularly LH, and their decrease lasted for at least 6 weeks after cessation of CyA (final levels; LH 28.2mIU/ml, FSH 69.8mIU/ml). On the other hand, serum testosterone level was low normal or slightly under normal, and no apparent changes could be seen during CyA treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1901552 TI - Cell cycle kinetics of human anagen scalp hair bulbs in thyroid disorders determined by DNA flow cytometry. AB - In both, 6 hyperthyroid and 6 hypothyroid patients as well as 10 healthy volunteers, cell cycle kinetics of dissected anagen scalp hair bulbs were determined by means of DNA flow cytometry (DNA-FCM). Compared with the healthy control group in patients with thyroid disorders striking differences of cell kinetic data were evaluated. In hyperthyroidism a significant increase (30%) and in hypothyroidism a significant decrease (15%) of S and G2+M phase cell percentages was found. The proliferation index (S+G2+M %) calculated revealed similar results. A correlation between the height of S phase percentages and plasma T3 levels was recognizable but could not be proven statistically. By means of DNA-FCM the study demonstrates for the first time the influence of thyroid hormones on in vivo cell cycle kinetics of human scalp hair bulbs. PMID- 1901553 TI - Do cutaneous coryneform bacteria produce short-chain fatty acids in vitro? AB - According to an opinion shared by many, human axillary and inguinal odour is related to short-chain fatty acids produced by gram-positive bacteria. Especially coryneform bacteria are said to produce these odiferous substances. After sampling 22 different strains of coryneform bacteria we cultured them for 48 h in a rich medium. Short-chain fatty acids were extracted afterwards by shaking the liquid medium with ether. Gas chromatography was used for detection. Only one of the tested bacteria produced propionic acid. Acetic acid, (iso)butyric acid or (iso)valeric acid could never be detected. The production of substances of the short-chain fatty acid type might, however, be a consequence of the particular substrate found under physiologic conditions by these organisms in human apocrine sweat. The theory that the metabolism of these skin bacteria necessarily produces short-chain fatty acids could not be supported. Another explanation might be that unspecific secreted enzymes of the bacteria are responsible for the production of short-chain fatty acids by a cleavage of skin surface lipids. PMID- 1901554 TI - Role of blood flow in adaptive protection of the cat gastric mucosa. AB - This study was designed to test the hypothesis that adaptive cytoprotection is related to increased blood flow caused by mild irritants. The stomach of cats was perfused with saline at pH 1.0. Mucosal blood flow was determined by radioactive microspheres, and celiac artery blood flow was measured by Doppler ultrasound. Gastric blood flow was left undisturbed or reduced by tightening a vessel loop around the celiac artery. Mucosal exposure to absolute ethanol for 2 minutes caused extensive damage to the surface epithelium, the pits, and the upper half of the glands. Pretreatment of the mucosa with 2 mol/L NaCl for 10 minutes prevented the development of mucosal lesions after subsequent application of absolute ethanol. The mucosal blood flow increased markedly after treatment with 2 mol/L NaCl. When this hyperemic response was inhibited by reducing celiac artery blood flow, ethanol caused lesions of similar degree as in animals not pretreated with 2 mol/L NaCl. A highly significant correlation was obtained between mucosal blood flow, as determined just before the application of ethanol, and the degree of ethanol-induced damage. At a chosen level of blood flow, ethanol caused the same degree of damage with or without pretreatment with 2 mol/L NaCl. In conclusion, high mucosal blood flow caused by a mild irritant is an important factor in adaptive gastric protection. With the present experimental setup, the protection could be fully explained as a result of the hyperemic response caused by 2 mol/L NaCl. PMID- 1901556 TI - A fallacy of intention-to-treat analysis. PMID- 1901555 TI - Secretory and metabolic effects of ethanol in the isolated amphibian gastric mucosa. AB - The effects of pure ethanol and some alcoholic beverages on acid secretion and metabolism were examined in the isolated toad gastric mucosa. Pure ethanol applied to the luminal side or to the submucosal side at low concentrations (2% 10%) was a potent stimulant of acid secretion, whereas high concentrations (greater than or equal to 20%) were inhibitory. Cimetidine and calcium-free solutions did not abolish the secretory effect of ethanol. Beer and wine, but not rum and whisky, caused a significant stimulation of acid secretion. Respiration was progressively increased by ethanol at concentrations between 2% and 20%. This effect was not affected by cimetidine or by SCH 28080, an inhibitor of the gastric hydrogen-potassium-stimulated adenosine triphosphatase. Ethanol (10%) significantly increased by 46% the tissue lactate-pyruvate ratio. The oxidations of glucose, butyrate, and acetate were progressively reduced by low concentrations of ethanol (5% and 10%). The results indicate that (a) low concentrations of ethanol and alcoholic beverages with low ethanol content are direct stimulants of acid secretion and (b) the secretory and metabolic effects of low concentrations of ethanol seem to be mediated via its oxidation. PMID- 1901557 TI - Sequencing reveals similarity of the wild-type div+ gene of Bacillus subtilis to the Escherichia coli secA gene. AB - We have determined the nucleotide (nt) sequence of the wild-type div+ gene of Bacillus subtilis which complements the temperature-sensitive div-341 mutation and is involved in cell septation, sporulation, secretion of extracellular enzymes, development of competence, autolysis and spore outgrowth. It has an open reading frame encoding 841 amino acids (aa) with homology to the Escherichia coli secA gene, which is involved in protein secretion and cell separation. The deduced aa sequence of the B. subtilis div+ gene shares 50% identity with that of the E. coli secA gene, and highly homologous regions were observed in the N terminal portions. DNA-DNA hybridization with the E. coli secA gene as the probe showed that the div+ gene could be easily detected by homology and that a single copy of the homologous gene was present in B. subtilis. Since both genes are similar in their functions and deduced aa sequences, we propose that the div+ gene is the counterpart of the secA gene of E. coli. PMID- 1901558 TI - The SFL2 (TUP1?) protein of Saccharomyces cerevisiae contains a repeating motif homologous to beta subunits of G proteins. PMID- 1901559 TI - Bacillus subtilis DNA polymerase III: complete sequence, overexpression, and characterization of the polC gene. AB - Genomic DNA encompassing polC, the structural gene specifying Bacillus subtilis DNA polymerase III (PolIII), was sequenced and found to contain a 4311-bp open reading frame (ORF) encoding a 162.4-kDa polypeptide of 1437 amino acids (aa). The ORF was engineered into an Escherichia coli expression plasmid under the control of the coliphage lambda repressor. Derepression of E. coli transformants carrying the recombinant vector resulted in the high-level synthesis of a recombinant DNA polymerase indistinguishable from native PolIII. N-terminal aa sequence analysis of the recombinant polymerase unequivocally identified the 4311 bp ORF as that of polC. Comparative aa sequence analysis indicated significant homology of the B. subtilis enzyme with the catalytic alpha subunit of the E. coli PolIII and, with the exception of an exonuclease domain, little homology with other DNA polymerases. The respective sequences of the mutant polC alleles, dnaF and ts-6, were identified, and the expression of specifically truncated forms of polC was exploited to assess the dependence of polymerase activity on the structure of the enzyme's C terminus. PMID- 1901560 TI - Isolation and developmentally regulated expression of an Aspergillus nidulans phenol oxidase-encoding gene, ivoB. AB - Ivory (ivo) mutants of Aspergillus nidulans lack conidiophore pigmentation. We have cloned ivoB which codes for a conidiophore-specific phenol oxidase (AHTase) via the adjacent selectable ureD gene. Gene-library transformants of a ureD4 strain proved defective for the vector, but we recovered both ureD and ivoB from a lambda library of transformant DNA. The ivoB transcription unit was localized to a SalI-XbaI 3-kb fragment and its 5' end was located by hybridization with an oligodeoxyribonucleotide corresponding to the N-terminal polypeptide sequence of AHTase. Expression of the ivoB 1.4-kb mRNA corresponded temporally with AHTase in conidiating cultures, and the levels of both mRNA and AHTase in leaky brlA mutants implied transcriptional control by brlA. A second developmentally regulated locus of unknown function adjacent to ivoB was also transcriptionally dependent on brlA, but was expressed 4 h later. PMID- 1901561 TI - Identification of a nucleotide sequence conserved in Lactococcus lactis bacteriophages. AB - A genetic element which is conserved in the genomes of numerous Lactococcus lactis bacteriophage isolates has been identified and its nucleotide sequence determined. Approximately 95-99% of all L. lactis bacteriophages collected over a period of six years from two geographically distinct sources carry this conserved DNA fragment. Genetic variation in other regions of the genomes of these bacteriophages is exhibited by changes in the overall restriction patterns. The complete nt sequence for a 1.6-kb region from nine independent L. lactis bacteriophage isolates was determined and only five changes in the nt sequence were observed within a span of 1536 bp. This region has a single large 1356-bp open reading frame (ORF) coding for a 51-kDa protein. Three out of the five changes occur in a 187-bp region, 5' to this large ORF. The two additional changes are found within the 1356-bp ORF, which results in two amino acid substitutions that do not, however, change the net charge of the protein. The encoded protein is extremely charged and shares some homology with yeast translation initiation factor. In addition, there is a potential zinc-binding domain within this protein, similar to those observed in genes from bacteriophages T4 and T7. PMID- 1901562 TI - A pilot study of fluticasone propionate in untreated coeliac disease. AB - Although gluten withdrawal is likely to remain the mainstay of treatment for adult coeliac disease, many patients find the diet inconvenient and unpalatable and compliance among asymptomatic patients is often poor. Oral corticosteroids have been used for patients who seem to be resistant to gluten withdrawal but preparations with low systemic bioavailability might be preferable. We have given a new glucocorticoid (fluticasone propionate) to 12 adults with untreated coeliac disease for six weeks while they were on a normal diet. One patient defaulted and one suffered a relapse in a pre-existing neoplasm. Excluding these, there was an improvement of symptoms, a mean weight gain of 2 kg, and a rise in albumin of 5.4 g/l. There was a significant improvement in the lactulose/mannitol excretion ratio (p less than 0.05) and in all histological variables examined in paired biopsy specimens (surface and crypt intraepithelial lymphocyte/enterocyte and goblet cell/enterocyte ratios and enterocyte height, p less than 0.01 or better). In six paired specimens sucrase and alkaline phosphatase activity increased in all (p less than 0.05) and lactase in five of six. No appreciable side effects were observed, but two patients had suppressed cortisol values and synacthen responses at six weeks. A further three, with normal pretrial results, had a blunted tetracosactrin response at six weeks. Fluticasone propionate seems worthy of further assessment in the treatment of coeliac disease as an adjunct to gluten withdrawal. PMID- 1901563 TI - Importance of local versus systemic effects of non-steroidal anti-inflammatory drugs in increasing small intestinal permeability in man. AB - Increased small intestinal permeability caused by non-steroidal anti-inflammatory drugs (NSAIDs) is probably a prerequisite for NSAID enteropathy, a source of morbidity in patients with rheumatoid arthritis. This increased small intestinal permeability may be a summation of a local effect during drug absorption, a systemic effect after absorption, and a local effect of the drug excreted in bile, but the relative contribution made by these factors is unknown. We assessed the effect of indomethacin and nabumetone on intestinal permeability. The principal active metabolite of nabumetone, 6-methoxy-2-naphthylacetic acid, is not subject to appreciable enterohepatic recirculation. Twelve volunteers were studied before and after one week's ingestion of indomethacin (150 mg/day) and nabumetone (1 g/day) with a combined absorption/permeability test. Neither drug had a significant effect on the permeation of 3-0-methyl-D-glucose, D-xylose, and L-rhamnose. Indomethacin increased the permeation of radioactive 51chromium ethylenediaminetetra-acetic acid (51Cr EDTA) significantly from baseline (mean (SEM) 0.63 (0.09)% v 1.20 (0.14)%, p less than 0.01) but nabumetone did not (0.70 (0.10)% p greater than 0.1). These results were supported by the 51Cr EDTA/L rhamnose urine excretion ratios, which reflect changes in intestinal permeability. They suggest that NSAIDs increase intestinal permeability during absorption or after biliary excretion and that the systemic effect is of minor importance. PMID- 1901564 TI - Megaduodenum due to hollow visceral myopathy successfully managed by duodenoplasty and feeding jejunostomy. AB - A 29 year old man with a history of childhood polymyositis developed insulin dependent diabetes and was found coincidentally to have chronic intestinal pseudo obstruction due to visceral myopathy. Multiple full thickness biopsy specimens showed severe disease in the duodenum and the proximal jejunum only, with less involvement distally. Total parenteral nutrition has been avoided for more than a year by enteral feeding through a fine bore jejunostomy catheter positioned with its tip in the distal jejunum. PMID- 1901565 TI - HCFA considers gradual approach to outpatient payment reform. AB - Government officials may advocate incremental reform of Medicare's outpatient payment system over more drastic measures, sources say. The Health Care Financing Administration has not yet made a decision on its recommendations for reform, which are due to Congress in September. Sources at HCFA say a full-scale reform plan may not be feasible now. Meanwhile, the Prospective Payment Assessment Commission, the congressional advisory panel responsible for reviewing HCFA's recommendation, has until March 1992 to turn in its report. Thus, October 1992 would be the earliest date for implementation. But some experts say even that's optimistic. PMID- 1901567 TI - Negative regulation of Bacillus subtilis sporulation by the spo0E gene product. AB - Transcription of the Bacillus subtilis spo0E gene is controlled by the AbrB transition state regulator. In AbrB+ strains, a single transcript, P1, was observed for the spo0E gene. In an abrB4 mutant strain, a second transcription start site 3 bases upstream from P1 was found to be used for the predominant transcript. P1 transcription was insensitive to the state of the abrB gene. Mutants carrying deletion or antibiotic cassette insertion mutations in the spo0E gene were Spo+. Multiple copies of the spo0E gene, not just the promoter region, were found to render strains incapable of sporulation. Spo+ strains that arose spontaneously from such Spo- strains were found to have deletions in the spo0E coding sequence on the plasmid. Strains carrying a deletion of the spo0E gene segregated Spo- colonies. These colonies were found to have secondary mutations in or near the spo0A, spo0B, or spo0F gene, suggesting that deletion of the spo0E gene results in increased pressure to sporulate that is compensated for by inactivation of one or more of the components of the signal transduction system leading to the initiation of sporulation. spo0E deletions were suppressors of the spo0F221 missense mutation but had no effect on the regulation of the spo0F, kinA, spo0A, or spo0B genes. The results suggest that the spo0E gene product is a negative regulator of the signal transduction pathway leading to sporulation. PMID- 1901566 TI - Isolation and characterization of the gene encoding the principal sigma factor of the vegetative cell RNA polymerase from the cyanobacterium Anabaena sp. strain PCC 7120. AB - The filamentous cyanobacterium Anabaena sp. strain PCC 7120 responds to combined nitrogen deprivation by forming specialized nitrogen-fixing cells at regular intervals along the filament. Genetic and biochemical studies have indicated that regulation of gene expression during differentiation occurs at the transcriptional level. As part of a characterization of RNA polymerase during differentiation, the gene encoding the 52-kDa principal sigma factor of the Anabaena sp. strain PCC 7120 vegetative-cell RNA polymerase was isolated by using an oligonucleotide probe based on the sequence of the N-terminal seven amino acids of the purified protein. sigA codes for a 390-amino-acid polypeptide that has a predicted molecular weight of 45,641. The amino acid sequence of the polypeptide encoded by sigA contains four regions corresponding to conserved domains of the principal RNA polymerase sigma factors of Escherichia coli (sigma 70) and Bacillus subtilis (sigma 43). Thus, although the subunit composition of cyanobacterial RNA polymerase core differs from that of other eubacteria (G. J. Schneider and R. Haselkorn, J. Bacteriol. 170:4136-4140, 1988), the principal sigma factor of at least one cyanobacterium is typically eubacterial. In contrast to sigma 70 and sigma 43 operon organization, sigA is monocistronic and encodes two transcripts of 1.7 and 2.2 kb. The abundance of the 1.7-kb transcript remains constant under both nitrogen-replete and nitrogen-limiting conditions, whereas the 2.2-kb transcript is induced following the removal of combined nitrogen. Continued or enhanced transcription of sigA under nitrogen starvation conditions is consistent with the observation that the principal RNA polymerase in differentiating cells contains SigA. PMID- 1901569 TI - Cell wall assembly in Bacillus megaterium: incorporation of new peptidoglycan by a monomer addition process. AB - The pattern of cross-linking in the peptidoglycan of Bacillus megaterium has been studied by the pulsed addition of radiolabeled diaminopimelic acid. The distribution of label in muropeptides, generated by digestion with Chalaropsis muramidase and separated by high-performance liquid chromatography, stabilized after 0.15 of a generation time. The proportion of label in the acceptor and donor positions of isolated muropeptide dimers stabilized over the same period of time. The results have led to the formulation a new model for the assembly of peptidoglycan into the cylindrical wall of B. megaterium by a monomer addition process. Single nascent glycan peptide strands form cross-linkages only with material at the inner surface of the wall. Maturation is a direct consequence of subsequent incorporation of further new glycan peptide strands, and there is no secondary cross-linking process. The initial distribution of muropeptides is constant. It follows that the final pattern of cross-linking in the wall is determined solely by, and can be forecast from, this repetitive pattern of incorporation. In a modified form, this model can also be applied to assembly of cell walls in rod-shaped gram-negative bacteria. PMID- 1901568 TI - Mutational analysis of the Bacillus subtilis DegU regulator and its phosphorylation by the DegS protein kinase. AB - The DegS-DegU protein kinase-response regulator pair controls the expression of genes encoding degradative enzymes as well as other cellular functions in Bacillus subtilis. Both proteins were purified. The DegS protein was autophosphorylated and shown to transfer its phosphate to the DegU protein. Phosphoryl transfer to the wild-type DegU protein present in crude extracts was shown by adding 32P-labeled DegS to the reaction mixture. Under similar conditions, the modified proteins encoded by the degU24 and degU31 alleles presented a stronger phosphorylation signal compared with that of the wild-type DegU protein. This may suggest an increased phosphorylation of these modified proteins, responsible for the hyperproduction of degradative enzymes observed in the degU24 and degU31 mutants. However, the degU32 allele, which also leads to hyperproduction of degradative enzymes, encodes a modified DegU response regulator which seems not to be phosphorylatable. The expression of the hyperproduction phenotype of the degU32 mutant is still dependent on the presence of a functional DegS protein. DegS may therefore induce a conformational change of the degU32-encoded response regulator enabling this protein to stimulate degradative enzyme synthesis. Two alleles, degU122 and degU146, both leading to deficiency of degradative enzyme synthesis, seem to encode phosphorylatable and nonphosphorylatable DegU proteins, respectively. PMID- 1901570 TI - Three-dimensional structure of the nickel-containing hydrogenase from Thiocapsa roseopersicina. AB - The three-dimensional structure of the nickel-containing hydrogenase from Thiocapsa roseopersicina has been determined at a resolution of 2 nm in the plane and 4 nm in the vertical direction by electron microscopy and computerized image processing on microcrystals of the enzyme. The enzyme forms a large ring-shaped complex containing six each of the large (62-kDa) and small (26-kDa) subunits. The complex is very open, with six well-separated dumbbell-shaped masses surrounding a large cylindrical hole. Each dumbbell is interpreted as consisting of one large and one small subunit. PMID- 1901571 TI - Adhesion of Actinomyces viscosus to Porphyromonas (Bacteroides) gingivalis-coated hexadecane droplets. AB - Interbacterial adhesion (coadhesion) is considered a major determinant of dental plaque ecology. In this report, we studied several aspects of the adhesion of Porphyromonas (Bacteroides) gingivalis to hexadecane in order to use the liquid hydrocarbon as a convenient substratum for coadhesion assays. Washed suspensions of hydrophobic P. gingivalis 2561 cells were vortexed with hexadecane to yield highly stable cell-coated droplets. Kinetics of coadhesion between Actinomyces viscosus cells and P. gingivalis-coated hexadecane droplets (PCHD) was subsequently studied. Aliquots of PCHD were added to A. viscosus suspensions, and the mixtures were gently rotated. Avid adhesion of A. viscosus cells to the immobilized P. gingivalis layer could be readily measured by the decrease in turbidity in the aqueous phase, following phase separation. Despite the ability of A. viscosus cells to adsorb to hexadecane following vigorous mixing, gentle mixing did not appreciably promote adhesion to bare hexadecane. Moreover, extensive microscopic examinations revealed that A. viscosus cells adhered exclusively to the bound P. gingivalis cells rather than to exposed areas of hexadecane. Coadhesion of A. viscosus to the PCHD appeared to follow first-order kinetics, attaining 80% levels within 30 min. Electron micrographs revealed A. viscosus cells adhering to the P. gingivalis cell layer adsorbed at the hexadecane-water interface. Interestingly, P. gingivalis cells did not appear to penetrate the hexadecane. A viscosus mutants lacking type 1 or type 2 fimbriae or both were still able to bind to the PCHD. No obvious correlation was observed between relative hydrophobicity of A. viscosus strains and their binding to PCHD. However, defatted bovine serum albumin, an inhibitor of hydrophobic interactions, was the most potent inhibitor among those tested. The data suggest that this approach provides a simple, quantitative technique for studying kinetics of bacterial coadhesion which is amenable to both light and electron microscopic observation. PMID- 1901572 TI - Differential regulation of spo0A transcription in Bacillus subtilis: glucose represses promoter switching at the initiation of sporulation. AB - We have shown by S1 nuclease mapping with in vivo transcripts that the differential expression of a sporulation-regulatory gene, spo0A, is regulated by switching of two discrete promoters during the initiation of sporulation in Bacillus subtilis; vegetative mRNA was transcribed from an upstream promoter (Pv, vegetative promoter), and sporulation-specific mRNA was transcribed from the other promoter (Ps, sporulation-specific promoter) about 150 bp downstream of the Pv promoter. Transcription from the Pv promoter was at a low level and shut off at T0.5. On the other hand, transcription from the Ps promoter was strongly induced at T0.5 and increased until T2.5. In the presence of 2% glucose, Pv directed transcription was not shut off and was observed even at T1.5, whereas the induction of Ps-directed transcription was completely repressed. A mutant in which the spo0A gene was transcribed only from the Ps promoter could sporulate normally in the presence of 0.1% glucose but could not sporulate at all in the presence of 2% glucose. In a catabolite-resistant sporulation mutant carrying crsA47 (sigA47), a mutation within the gene encoding sigma A, normal promoter switching from Pv to Ps was observed in the presence of 2% glucose. PMID- 1901574 TI - Acetate catabolism in the dissimilatory iron-reducing isolate GS-15. AB - Acetate-grown GS-15 whole-cell suspensions were disrupted with detergent and assayed for enzymes associated with acetate catabolism. Carbon monoxide dehydrogenase and formate dehydrogenase were not observed in GS-15. Catabolic levels of acetokinase and phosphotransacetylase were observed. Enzyme activities of the citric acid cycle, i.e., isocitrate dehydrogenase, 2-oxoglutarate sythase, succinate dehydrogenase, fumarase, and malate dehydrogenase, were observed. PMID- 1901573 TI - The Yersinia pestis V antigen is a regulatory protein necessary for Ca2(+) dependent growth and maximal expression of low-Ca2+ response virulence genes. AB - The low-Ca2+ response is a multicomponent virulence regulon of the human pathogenic yersiniae in which 12 known virulence genes are coordinately regulated in response to environmental cues of temperature, Ca2+, and nucleotides such as ATP. Yersinial growth also is regulated, with full growth yield being permitted at 37 degrees C only if Ca2+ or a nucleotide is present. In this study, we constructed and characterized a mutant Yersinia pestis specifically defective in the gene encoding the V antigen, one of the virulence genes of the low-Ca2+ response. An in-frame internal deletion-insertion mutation was made by removing bases 51 through 645 of lcrV and inserting 61 new bases. The altered lcrV was introduced into the low-Ca2+ response plasmid in Y. pestis by allelic exchange, and the resulting mutant was characterized for its two-dimensional protein profiles, growth, expression of an operon fusion to another low-Ca2+ response virulence operon, and virulence in mice. The mutant had lost its Ca2+ and nucleotide requirement for growth, showed diminished expression of Ca2(+)-and nucleotide-regulated virulence genes, and was avirulent in mice. The mutation could be complemented with respect to the growth property by supplying native V antigen operon sequences in trans in high copy number (on pBR322). Partial complementation of the growth defect and almost complete complementation of the virulence defect were seen with a lower-copy-number complementing replicon (a pACYC184 derivative). The data are consistent with the interpretation that V antigen is bifunctional, with a role in regulating growth and expression of low Ca2+ response virulence genes in addition to its putative role as a secreted virulence protein. PMID- 1901577 TI - Frequency-dependent viability in mutant strains of Drosophila melanogaster. AB - We investigated the effects of genotypic frequencies on egg-to-adult viabilities in pairwise combinations of four strains of Drosophila melanogaster. The experiments involved mixture of a total of 42,000 eggs in varying proportions under controlled densities and observation of surviving adults. Viabilities were found to depend on frequencies in several genotypic combinations. In the most extreme case, the absolute viability of cn;bw females increased monotonically from 54% when common to 70% when rare. The results illustrate several statistical and methodological problems that might explain why some experiments have failed to detect frequency-dependent viabilities. These problems include heterogeneity between replications, sex differences in susceptibility to competition, and strong dependence of the experimental outcome on the choice of competitor genotypes. PMID- 1901576 TI - Distribution and developmental expression of the nerve terminal protein NT75 in the rat cerebellum. AB - Previous studies of the nerve terminal protein NT75 in the developing spinal cord have suggested an association between the appearance of NT75 immunoreactivity and the process of synaptogenesis. To examine the time course of NT75 expression further, the current study compared the localization of NT75 and the synaptic vesicle protein synaptophysin in the adult and developing rat cerebellum and in cerebellar tissue cultures. In the adult cerebellum, dense NT75 staining is confined to the molecular layer, where it is associated with parallel fiber endings of cerebellar granule cells. During development, NT75 immunoreactivity is first detectable in the cerebellar cortex as a dense band of staining in the deepest portion of the molecular layer at postnatal day 10. The stained zone expands to occupy a progressively greater portion of the molecular layer until about postnatal day 20. Synaptophysin staining occurs in granule cell processes earlier than NT75 and is found throughout the molecular layer by postnatal day 7. Quantitatively, rapid increases in both NT75 and synaptophysin occur in the first three postnatal weeks, with NT75 activity reaching levels exceeding the adult value by 50% over postnatal days 20 through 30, whereas synaptophysin plateaus at near adult levels by postnatal day 20. In cerebellar cultures, NT75 staining in neurites develops over several days, increasing coincidentally with development of synaptic contacts, whereas synaptophysin staining is already present in most neurites after only 1 day in vitro. The results indicate that NT75 expression in developing cerebellar granule cell nerve terminals is closely associated with the appearance of mature nerve terminals, suggesting that the protein may have a role in the formation/stabilization of the synaptic ending or in the mechanisms of synaptic transmission. PMID- 1901575 TI - A vector for analysis of promoters in the cyanobacterium Anabaena sp. strain PCC 7120. AB - A plasmid vector containing a multiple-cloning site followed by a promoterless chloramphenicol acetyltransferase (cat) gene, protected by transcription terminators and mobilizable by conjugation from Escherichia coli into Anabaena sp. strain PCC 7120, was constructed. The utility of the vector was shown by deletion analysis of the promoter region of the Anabaena psbB gene. PMID- 1901578 TI - Highly conserved segments in mammalian chromosomes. AB - Mammalian chromosomes from seven species for which gene maps exist were studied by high-resolution techniques to identify areas of conserved chromosome banding homology. High-resolution comparisons of human, chimpanzee, gorilla, orangutan, African green monkey, cat, and mouse chromosomes revealed regions of apparently conserved chromosomal banding, which may indicate the likely positions of conserved linkage in the phylogeny of mammals. This analysis indicates that many regions of subbanding homology may have remained intact during the evolution of mammals and reflects a high degree of chromosome conservation in diverse species. PMID- 1901579 TI - Coadaptation revisited. AB - During the four decades or more since Dobzhansky introduced the term "coadaptation" to refer to the commonly observed selective superiority of inversion heterozygotes in populations of Drosophila pseudoobscura, the definition of the term has evolved, as have views concerning the rapidity with which coadaptation might occur. Indeed, the paucity of demonstrated instances of linkage disequilibrium in natural populations has led many to dismiss coadaptation as a factor in evolutionary change. The present article reviews the reasons why coadaptation (and the equivalent expression, "integration of gene pools") was proposed as a phenomenon occurring in local (or experimental) populations, offers supporting data obtained through a reanalysis of data on irradiated populations of D. melanogaster, and concludes that sound evidence supports coadaptation as a factor in the genetic change of populations. PMID- 1901581 TI - Calculation of affinity constants directly from homologous displacement curves. AB - Homologous displacement experiments are described in which the binding of labelled ligand (tracer) was inhibited with the same ligand unlabelled (inhibitor). Data were evaluated with a direct curve-fitting method. The equation used employs the concentration of unlabelled ligand as the independent variable and the fraction of tracer bound (p) as the dependent variable. The other entities of the equation are the dissociation constant (Kd), the maximal fraction of tracer bound (Po) and the tracer concentration (T). Different options exist regarding the insertion of Po and T as parameters or constants in the curve fitting. When applied to experimental data obtained from the binding of dinitrophenyl-hapten by a monoclonal antibody, the least interexperimental variation in affinity was obtained when both Kd and Po were estimated as parameters, and T was inserted as a constant. This calculation procedure achieves more reproducible results than those obtained with the Scatchard plot and the Langmuir curve, even after exclusion of the most scattered data points. PMID- 1901580 TI - Ultrasensitive assays for endogenous antimicrobial polypeptides. AB - We developed two sensitive methods for identifying antimicrobial molecules in leukocytes and other tissues. One method uses a gel overlay technique and was designed to identify antimicrobial polypeptides in samples subjected to polyacrylamide gel electrophoresis. The other, a radial diffusion assay, allows multiple fractions obtained by chromatographic procedures to be tested for antimicrobial activity conveniently. When we used E. coli ML-35p or Salmonella typhimurium 14028S as test organisms in the radial diffusion assay, we routinely detected 5-10 ng of rabbit defensin NP-1 in 5 microliters of sample. With minor modifications, both methods can be applied to other organisms, including Gram positive bacteria, several Candida species and Cryptococcus neoformans. PMID- 1901582 TI - [Studies on chemotherapy in adenocarcinoma of the uterine cervix using xenografts transplanted in nude mice]. AB - Adenocarcinoma of the human uterine cervix was successively transplanted into nude mice and the effects of chemotherapy on adenocarcinoma of uterine cervix were investigated in this transplanted tumor. First, it was confirmed that both the original tumor and the transplanted tumor were apparently histologically the same as adenocarcinoma of the uterine cervix (endocervical type). And the transplanted tumor was shown to have the features of adenocarcinoma by observation it under an electron microscope. The doubling time of the transplanted tumor was 9.2 +/- 1.4 days (means +/- SD). For the chemotherapy study, first the therapeutic effects of 11 kinds of agents were screened by single-agent chemotherapy applied to the transplanted tumor. From the results of this series, 6 regimens for multi-agent chemotherapy were tried on the transplanted tumor. The effects of the chemotherapy were evaluated following Battelle Columbus Laboratories Protocol and histopathologically. The relative regression rates for the tumors treated with mitomycin C(MMC) + cyclophosphamide (CPM) and MMC + CPM + methotrexate (MTX) were 72.9% and 80.9% (Tn/T0 = 0.84), respectively. Histological effects were found in only these. The results suggest that the combinations of MMC + CPM or MMC + CPM + MTX are regimens that are possibly effective on the adenocarcinoma of human uterine cervix and are worth be trying clinically. PMID- 1901583 TI - [Effects of buserelin presurgical treatment on vascularity in the sub-serosal interstitial tissue of the uterus and operative blood loss at hysterectomy in women with uterine leiomyoma and adenomyosis]. AB - We examined 194 cases of uterine leiomyoma and adenomyosis who received total abdominal hysterectomy, in order to compare the effect of presurgical medical treatment such as with Buserelin, Danazol and Pill, on operative blood loss with non-treated group. The operative blood loss was 314.0 +/- 177.2 ml (mean +/- SD) in the control group (n = 145), 211.2 +/- 64.1 ml in the Buserelin-treated group (n = 26), 276.8 +/- 110.7 ml in the Danazol-treated group (n = 10), and 396.6 +/- 213.1 ml in the Pill-treated group (n = 13). The operative blood loss in the Buserelin-treated group was significantly lower than in the control group (p less than 0.01) and in the Pill-treated group (p less than 0.05). After considering the pathology of the uterus, the uterine size, and the level of expertise of the surgeon, the operative blood loss in the Buserelin-treated group was significantly lower than in the control group. We measured the capillary space, small arteries and veins in the sub-serosal interstitial tissue of the uterus, and observed that the vascular space decreased significantly (p less than 0.01) in the Buserelin-treated group compared to the control group. From these facts it may be concluded that Buserelin presurgical treatment reduces the operative blood loss at hysterectomy, and it seems very likely that the decrease in vascularity may play an important role. PMID- 1901584 TI - [A case of catamenial epilepsy with repeated psychomotor seizure]. PMID- 1901586 TI - Evidence for the control of testicular interstitial fluid volume in the rat by specific germ cell types. AB - Following on from our recent evidence that Sertoli cells may regulate testicular interstitial fluid (IF) volume, this study has assessed whether depletion of specific germ cell types in vivo is associated with changes in recovered IF volume. Germ cell depletion was induced by either a single oral administration of 650 mg methoxyacetic acid (MAA)/kg or exposure of the testes to local heating (43 degrees C for 30 min). Treatment with MAA induced depletion or loss of most pachytene and later spermatocytes at 1-3 days and, because of maturation depletion, this resulted in the specific depletion of later germ cell types at 7 35 days. Testicular IF volume was unchanged at 1-7 days after MAA treatment but was increased significantly (P less than 0.01) at 14 days and was nearly doubled (P less than 0.001) at 21 days, before returning to control levels at 28-42 days. Serum LH (and FSH) levels were generally higher in MAA-treated rats, especially at 21 and 28 days, but there was no obvious correlation between LH levels and IF volume changes. Similarly, there was no relationship between IF volume changes and testicular weight or IF levels of testosterone. The increase in IF volume at 14-21 days after MAA treatment coincided with specific depletion of the later elongate spermatids (steps 14-19) and, when these cells reappeared in the testis, IF volume normalized. This possible causal association was studied further in rats exposed to local testicular heating which, within 3 days, caused major depletion of pachytene spermatocytes and early (step 1-8) spermatids.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1901585 TI - [Diagnosis of antiphospholipid syndrome evaluated by the standard serum and its clinical application for recurrent fetal loss]. PMID- 1901587 TI - Effects of bovine follicular fluid on the secretion of LH and FSH in inhibin immunized seasonally anoestrous ewes. AB - It has been shown previously that treatment of seasonally anoestrous ewes with steroid-free bovine follicular fluid (FF), a crude inhibin-containing preparation, leads to a decrease in plasma FSH level which is accompanied by a marked increase in pulsatile LH secretion. Since FF contains several factors (e.g. activin, follistatin, unidentified components) other than inhibin, which might act to modify gonadotrophin secretion, it was of interest to establish whether these concurrent effects of FF on FSH and LH secretion persisted in ewes which had been actively immunized against a synthetic peptide replica of the alpha subunit of bovine inhibin. In June 1989 (anoestrous period) groups of inhibin-immune and control ewes (n = 5 per group) received 6-hourly s.c. injections of either bovine serum (2 ml) or one of two doses of FF (0.5 ml or 2 ml) for 3 days. Blood was withdrawn at 6-h intervals for 6 days beginning 24 h before the first injection. On the final day of treatment, additional blood samples were withdrawn at 15-min intervals for 8 h to monitor pulsatile LH secretion. Ewes were then challenged with exogenous gonadotrophin-releasing hormone (GnRH; 2 micrograms i.v. bolus) to assess pituitary responsiveness. In control ewes, FF promoted a dose-dependent suppression of basal (maximum suppression 65%; P less than 0.01) and post-GnRH (maximum suppression 72%; P less than 0.01) levels of FSH in plasma. This was accompanied by an increase (P less than 0.01) in LH pulse frequency from 1.40 +/- 0.24 (S.E.M.) to 3.20 +/- 0.37 pulses/8 h. In contrast, FF did not affect secretion of either FSH or LH in inhibin-immunized ewes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1901588 TI - Effects of luteolysis during late pregnancy on pituitary responsiveness to gonadotrophin-releasing hormone in the rat. AB - We investigated whether the increase in the gonadotrophin response to gonadotrophin-releasing hormone (GnRH) during the last days of pregnancy and the occurrence of parturition on day 22 of pregnancy in rats are due to the increase in the plasma concentrations of oestradiol-17 beta after luteolysis, which occurs around day 20. In a first series of experiments we studied the effects of s.c. implantation of two capsules containing oestradiol on basal and GnRH-stimulated secretion of LH and FSH before and after luteolysis. Before luteolysis, ovariectomy increased basal LH and FSH; oestradiol treatment prevented this increase partly (FSH) or completely (LH). Ovariectomy also lowered the LH response to the infusion of GnRH (100 ng/h). Oestradiol treatment on the other hand, increased the LH and FSH responses of both intact and ovariectomized rats above the level in intact non-treated control rats. After luteolysis, ovariectomy increased basal FSH only. Treatment with oestradiol did not prevent the increase in basal FSH and ovariectomy diminished the LH response to GnRH infusion. Oestradiol treatment maintained the LH response in ovariectomized rats at the control level and increased the FSH responses of both intact and ovariectomized rats to a higher level than in control rats. Furthermore, the LH and FSH responses of the oestradiol-treated groups of intact and ovariectomized rats were higher after luteolysis than before. In a second series of experiments two capsules containing progesterone were s.c. implanted before or after luteolysis. Progesterone treatment suppressed the plasma concentration of oestradiol and the gonadotrophin responses to infusion of GnRH on the expected day of parturition in both groups of rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1901589 TI - The effect of genetic selection for milk yield on the response to growth hormone secretagogues in immature cattle. AB - Eighty 4-month-old calves of both sexes and of two selected lines differing by 70 kg in their predicted total yield of milk fat and protein were injected intravenously with three of four GH secretagogues: these were, per kg liveweight; (i) 0.2 micrograms human GH-releasing factor (1-29) (GRF), (ii) 0.2 micrograms TRH, (iii) a combination of (i) and (ii), and (iv) 0.1 g arginine hydrochloride. The response of GH was measured for 2 h following administration. Geometric mean concentration of the 5-, 10-, 15-, and 20-min samples following GRF, TRH and their combination were 29.3, 19.5 and 156 micrograms/l compared with baseline means of 6.5, 10.0 and 12.6 micrograms/l respectively, and for arginine (in which the mean response included the 30-min instead of the 5-min sample) 14.6 micrograms/l compared with a baseline of 8.31 micrograms/l. The line selected for greater yield responded more to each secretagogue by 1.53-fold following GRF (P less than 0.01), 1.34-fold following TRH (P less than 0.05), 1.11-fold following the combination (P greater than 0.01) and 1.26-fold following arginine (P less than 0.1). Females responded 2.3-fold more than males following GRF administration (P less than 0.001), only 1.2-fold more following TRH (P greater than 0.1), but less (0.63-fold) than males when GRF was combined with TRH (P less than 0.05). For all secretagogues the concentration of GH before administration was important in determining the size of response (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1901590 TI - Effect of basal and pulsatile LH release on FSH-stimulated follicle growth in ewes chronically treated with gonadotrophin-releasing hormone agonist. AB - Ewes chronically treated with gonadotrophin-releasing hormone (GnRH) agonist were used to investigate the importance of the peripheral concentration of LH in FSH stimulated follicular development. Twenty-four Welsh Mountain ewes were treated with two agonist implants containing 3.3 mg buserelin. During week 6 of treatment all the ewes were given a 72-h continuous infusion of ovine FSH alone (3 micrograms/h) or FSH with large (7.5 micrograms)- or small (2.5 micrograms) amplitude pulses of ovine LH delivered at 4-hourly intervals. The importance of baseline LH throughout the FSH infusion was evaluated in six animals which were treated with a specific antiserum against bovine LH (LH-AS) 15-20 h before the start of FSH treatment. In the absence of LH-AS, infusion of FSH alone or with large or small pulses of LH stimulated the development of a normal number of small follicles (less than or equal to 2.5 mm in diameter) and large follicles (greater than 2.5 mm in diameter). These follicles had normal diameter and steroid secretion compared with control ewes on day 8 of the luteal phase. In contrast, the animals pretreated with LH-AS developed no follicles greater than 2.0 mm in diameter but the number of small follicles per ewe was significantly (P less than 0.05) increased. These results support the hypothesis that FSH in the absence of pulsatile LH release stimulates preovulatory follicular development in ewes treated with GnRH agonist. The follicular response to LH pulses of different amplitude is dependent on both the stage of development of the follicle and the peripheral concentration of FSH.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1901591 TI - Glycosphingolipid glycosyltransferases in human fetal brain. AB - The developmental pattern of gangliosides in human fetal brain should reflect the activities of the respective glycosyltransferases. LA2-synthase activity, along with that of GM3-, GD3-, GM2-, and GM1-synthases, was determined in human fetal brain at 10-22 weeks of gestation. LA2-synthase is the pivotal enzyme in lacto series ganglioside formation. LA2-synthase activity decreased during the study period, mirroring a similar temporal decline in levels of the lacto series gangliosides, particularly 3'-isoLM1. The developmental profiles of the ganglio series glycosyltransferase activities demonstrate distinct changes that correspond to the ganglioside pattern between fetal weeks 10 and 22. In particular, the marked increase in GM2-synthase activity at 20 and 22 weeks of gestation and the decline in GD3-synthase activity after 15 weeks could explain the prominent expression of the a series gangliosides in this period of rapid neuronal outgrowth. However, a similar decline (two- to 2.5-fold) in GM3-synthase activity suggests a more likely conclusion, namely, that the two sialyltransferase activities are derived mainly from astroglial cells, which show a marked proliferation during the 10-15th fetal weeks. The data do not negate the hypothesis that GM3- and GD3-synthase are the critical enzymes in the regulation of ganglioside biosynthesis but do indicate a need to reevaluate the significance of GM2-synthase in expression of the a series gangliosides. PMID- 1901592 TI - Synapsins contain O-linked N-acetylglucosamine. AB - The neuron-specific synaptic vesicle-associated phosphoproteins synapsin I and synapsin II were shown to contain terminal N-acetylglucosamine (GlcNAc) residues as determined by specific labeling with bovine galactosyltransferase and UDP [3H]galactose. The beta-elimination of galactosyltransferase radiolabeled synapsin I and subsequent analysis of released saccharide on high-voltage paper electrophoresis confirmed the presence of monosaccharidic GlcNAc moieties in O linkage to the protein. Partial cleavage of synapsin I by collagenase, 2-nitro-5 thiocyanobenzoic acid, and Staphylococcus aureus V8 protease suggests that at least three glycosylation sites exist along the molecule. Taken together these data present the first evidence that a neuron-specific protein contains O glycosidically bound GlcNAc. PMID- 1901593 TI - Effects of a new thyrotropin releasing hormone analogue, YM-14673, on the in vivo release of acetylcholine as measured by intracerebral dialysis in rats. AB - The effects of a new thyrotropin releasing hormone (TRH) analogue, YM-14673 (N alpha-[[(S)-4-oxo-2-azetidinyl]carbonyl]-L-histidyl-L-prolinamide dihydrate), on the release of acetylcholine (ACh) in free-moving rats were examined in vivo by intracerebral dialysis. In the frontal cortex, YM-14673 (0.1-0.3 mg/kg) caused a significant dose-dependent increase in the extracellular levels of ACh, suggesting that YM-14673 stimulated the ACh release. These actions of YM-14673 were about 50 times more potent than those of TRH. On the other hand, extracellular levels of ACh in caudate nucleus were not changed following injection of YM-14673 even at 3 mg/kg. TRH and methamphetamine also increased the release of ACh in frontal cortex. Haloperidol prevented the increase in the methamphetamine-induced release of ACh, whereas the increased release of ACh produced by YM-14673 was partially antagonized by haloperidol. These results suggest that the dopaminergic system affects the facilitatory effects on the ACh release in the frontal cortex and that the stimulatory effect of YM-14673 on the frontal cholinergic neurons is partially mediated by dopaminergic neurons. PMID- 1901594 TI - Changes in organization and axonal transport of cytoskeletal proteins during regeneration. AB - Changes in solubility and transport rate of cytoskeletal proteins during regeneration were studied in the motor fibers of the rat sciatic nerve. Nerves were injured by freezing at the midthigh level either 1-2 weeks before (experiment I) or 1 week after radioactive labeling of the spinal cord with L [35S]methionine (experiment II). Labeled proteins in 6-mm consecutive segments of the nerve 2 weeks after labeling were analyzed following fractionation into soluble and insoluble populations with 1% Triton at 4 degrees C. When axonal transport of newly synthesized cytoskeleton was examined in the regenerating nerve in experiment I, a new faster component enriched in soluble tubulin and actin was observed that was not present in the control nerve. The rate of the slower main component containing most of the insoluble tubulin and actin together with neurofilament proteins was not affected. A smaller but significant peak of radioactivity enriched in soluble tubulin and actin was also detected ahead of the main peak when the response of the preexisting cytoskeleton was examined in experiment II. It is thus concluded that during regeneration changes in the organization take place in both the newly synthesized and the preexisting axonal cytoskeleton, resulting in a selective acceleration in rate of transport of soluble tubulin and actin. PMID- 1901595 TI - Characteristics of [3H]GBR 12935 binding in the human and rat frontal cortex. AB - Binding characteristics of the selective dopamine uptake inhibitor [3H]GBR 12935 have been described for the striatum but not for the frontal cortex. We have developed assay conditions for quantifying [3H]GBR 12935 binding in the frontal cortex. In both the rat and human frontal cortex, the assay required four times more tissue (8 mg/ml) than in the striatum (2 mg/ml). [3H]GBR 12935 binding in the frontal is complex, as it involves multiple binding sites. The high-affinity binding site is sodium dependent and is inhibited by sodium. In human but not in rat frontal cortex, addition of K+ reversed the sodium inhibition. The pharmacological profile of the high-affinity [3H]GBR 12935 binding site is consistent with that of the dopamine transporter, because drugs with the most selective dopamine reuptake blocking activities are the most potent displacers of [3H]GBR 12935 binding. There is a positive correlation between the rat and human inhibitory constants, a finding indicating that there are similar pharmacological profiles across at least these two species. Rats with a 6-hydroxydopamine lesion had a 47% decrease in number of [3H]GBR 12935 binding sites, a result indicating that at least a portion of these sites had been on presynaptic dopamine terminals. PMID- 1901596 TI - Potassium- and carbachol-evoked release of [3H]noradrenaline from human neuroblastoma cells, SH-SY5Y. AB - The human neuroblastoma clone SH-SY5Y expresses potassium-, carbachol-, and calcium ionophore A23187-evoked, calcium-dependent release of [3H]noradrenaline. Release in response to carbachol and potassium was greater than additive. Atropine (Ki = 0.33 nM), hexahydrosiladifenidol (Ki = 18 nM), and pirenzepine (Ki = 1,183 nM) completely inhibited the carbachol-evoked noradrenaline release, an order of potency suggesting that an M3 receptor was linked to release. In contrast, noradrenaline release was only partially inhibited by the M2-selective antagonists methoctramine (10(-4) M) and AFDX-116 (10(-4) M), by approximately 14 and 46%, respectively. The nicotinic antagonist d-tubocurarine (10(-4) M) resulted in a partial inhibition of release, a finding suggesting that a nicotinic receptor may also be involved. SH-SY5Y provides a suitable cell line in which to study the biochemical mechanisms underlying the cholinergic receptor regulation of noradrenaline release. PMID- 1901597 TI - Management of chiasmal and hypothalamic gliomas of infancy and childhood with chemotherapy. AB - Between March, 1983, and February, 1989, 19 infants or children with chiasmal/hypothalamic gliomas were treated with chemotherapy after either surgical or radiological diagnosis. The patients ranged in age from 15 weeks to 15.6 years (median 3.2 years) at the start of therapy. Twelve patients were treated immediately after diagnosis because of progressive symptoms, and seven received chemotherapy after either radiographic progression or clinical deterioration, including progressive visual loss or intracranial hypertension. Based on biopsy results, seven of these tumors were classified as juvenile pilocytic astrocytomas, two as astrocytomas, two as highly anaplastic astrocytomas, and one as a subependymal giant-cell astrocytoma. There was associated neurofibromatosis in four patients. The two initial patients were treated with either actinomycin D and vincristine or 5-fluorouracil, hydroxyurea, and 6-thioguanine. The remaining patients received nitrosourea-based therapy; 15 evaluable patients were treated with a five-drug regimen that included 6 thioguanine, procarbazine, dibromodulcitol, 1-(2-chloroethyl)-3-cyclohexyl-1 nitrosourea (CCNU), and vincristine and one received 1,3-bis(2-chloroethyl)-1 nitrosourea (BCNU) and 5-fluorouracil. Fifteen of the 18 evaluable patients initially managed with chemotherapy either responded to therapy or their condition stabilized. Median time to tumor progression has not been reached at a median follow-up period of 79 weeks (range 6.6 to 303 weeks), and no tumor related death has occurred with a median follow-up period of 79 weeks (range 18 to 322 weeks) from the initiation of therapy. The four patients who failed therapy or whose disease progressed after chemotherapy were treated satisfactorily with radiation therapy. Initial improvement or stabilization of visual function was obtained in 16 patients. Endocrine function remained stable in all patients during treatment, although three patients required pharmacological treatment for endocrinopathy that was present at diagnosis. These preliminary results suggest that nitrosourea-based cytotoxic regimens are useful for the initial treatment of children with chiasmal/hypothalamic gliomas, and allow potentially harmful radiation therapy to be deferred until progression of disease. PMID- 1901598 TI - The morbidity of long-term seizure monitoring using subdural strip electrodes. AB - The authors report a prospective study of morbidity associated with long-term seizure monitoring using subdural strip electrodes. Three hundred fifty patients were divided into two groups: 175 patients received antibiotics intravenously during the entire period that the electrodes were implanted, and 175 patients received one dose of antibiotics on the morning of surgery. In the group given continuous antibiotic coverage there were two cases of meningitis, both treated without sequelae. In the group receiving one dose of antibiotics, one patient had a brain abscess and three had superficial wound infections. There were no other instances of major morbidity or mortality in either group of patients. The total morbidity rate for both serious and minor complications was 0.85%. PMID- 1901599 TI - Altered gastric emptying in the head-injured patient: relationship to feeding intolerance. AB - Most patients with moderate to severe head injury initially do not tolerate enteral feedings postinjury. This intolerance is more prolonged than that found in patients suffering other types of trauma. The authors prospectively evaluated 12 patients with moderate to severe head injury (Glasgow Coma Scale score between 4 and 10) throughout their hospitalization for liquid gastric emptying as a possible mechanism for intolerance to enteral feeding. During Week 1, the majority of patients displayed a delay in gastric emptying. Patients also displayed an abnormal biphasic response (gastric emptying faster than normal during the early stage but prolonged later). By Week 2, many patients still had delayed and abnormal biphasic responses to gastric emptying. By Week 3, an improvement was observed with the majority of patients exhibiting rapid gastric emptying, but delays and abnormal biphasic responses were still seen. Patients who initially had rapid or normal gastric emptying tolerated full-strength full rate feedings significantly earlier compared with those who experienced delayed gastric emptying (8.5 +/- 0.5 days vs. 13.7 +/- 3.2 days, p less than 0.001). All patients tolerated full-strength full-rate feedings by Day 16 postinjury (range 7 to 16 days) except the two patients who displayed delayed gastric emptying for prolonged periods of time (mean 25 days). This is the first study to longitudinally evaluate gastric emptying following head injury. The authors suggest that patients with moderate to severe head injury often experience alterations in gastric emptying which may affect their ability to tolerate enteral feedings. PMID- 1901600 TI - Effect of intrathecal fibrinolysis on cerebrospinal fluid absorption after experimental subarachnoid hemorrhage. AB - The effect of intrathecal fibrinolysis on cerebrospinal fluid (CSF) absorption was investigated after experimental subarachnoid hemorrhage (SAH). In 11 cats, SAH was induced by intracisternal application of 1 to 4 ml of fresh autologous blood. Thirty minutes after the experimental SAH, the CSF outflow resistance was found to be elevated from a median of 77 mm Hg/ml/min (range 41.3 to 109 mm Hg/ml/min) to a median of 580 mm Hg/ml/min (range 104 to 7000 mm Hg/ml/min). A logarithmic relationship could be demonstrated between the volume of subarachnoid blood and the elevation of the CSF outflow resistance. The intrathecal application of 2 mg of recombinant tissue plasminogen activator (rt-PA), which is a fibrinolytic substance suitable for lysis of subarachnoid blood clots in man, resulted in an almost total restoration of CSF absorption after experimental SAH. The CSF outflow resistance after SAH was lowered by application of rt-PA from a median of 1028.05 mm Hg/ml/min (range 394 to 7000 mm Hg/ml/min) to 79 mm Hg/ml/min (range 56.7 to 223 mm Hg/ml/min). It is concluded that the impairment of CSF absorption after SAH may play an important role in the pathogenesis of post-hemorrhagic vasospasm. PMID- 1901601 TI - Lysis of intraventricular hematoma with tissue plasminogen activator. Case report. AB - A 42-year-old woman suffered a severe intracerebral and intraventricular hemorrhage from a ruptured anterior cerebral artery aneurysm. Evacuation of the frontal hematoma and clipping of the aneurysm was performed but the intraventricular blood clot persisted, causing ventricular dilatation and high intracranial pressure (ICP) 24 hours after surgery despite external ventricular drainage. Over this period of time the patient's clinical condition improved from Grade V to Grade IVb (World Federation of Neurological Surgeons classification). The intraventricular hematoma was lysed with a total of 8 mg recombinant tissue plasminogen activator injected directly into the ventricles on the 1st and 2nd postoperative days, resulting in rapid normalization of ventricular size and ICP. The patient has since made a substantial recovery and has been able to return home. PMID- 1901602 TI - Tissue plasminogen activator thrombolysis of a middle cerebral artery embolus in a patient with an arteriovenous malformation. Case report. AB - A patient harboring a cerebral arteriovenous malformation (AVM) underwent angiography in an attempt to embolize the AVM. During catheterization (and prior to embolization) he became hemiplegic and aphasic. Angiography revealed a complete middle cerebral artery (MCA) occlusion by an embolus. The patient was treated with recombinant tissue plasminogen activator (t-PA), a thrombolytic agent. Restoration of MCA flow was achieved, and the patient recovered. Immediately after MCA embolus, t-PA infusion may lead to thrombolysis and neurological recovery. The decision-making process as well as the risks associated with the use of t-PA are discussed. PMID- 1901603 TI - Analysis of protein transport through the Golgi in a reconstituted cell-free system. AB - The processes which transport membrane proteins between compartments of the Golgi apparatus have been reconstituted in vitro using isolated Golgi fractions. This cell-free system allows a detailed analysis of protein transport not possible in intact cells. Transport of the membrane glycoprotein (G protein) of vesicular stomatitis virus (VSV) is measured from a "donor" to an "acceptor" Golgi fraction. The donor Golgi fraction is prepared from VSV-infected Chinese hamster ovary (CHO) mutant cells deficient in the glycosylation enzyme N acetylglucosamine transferase I. "Acceptor" is prepared from uninfected wild-type CHO cells. Transport is measured by the addition of N-acetylglucosamine to G protein, which can occur only upon movement of G protein from donor to acceptor. Transport requires physiological pH and osmolarity, is dependent on nucleotide triphosphates, and is mediated by proteins both from cytosol and on the Golgi membranes. Protein movement is inhibited by the non-hydrolyzable GTP analogue, GTP gamma S. The process of transport proceeds through the budding, pinching off, targeting, and fusion of transport vesicles. In this system these vesicles are initially coated with a non-clathrin coat and are targeted with this coat intact. Several of the proteins which mediate transport have been characterized, and isolated to homogeneity. The successful development of this assay has led to the formulation of cell free assays for protein transport between other compartments. Comparison of these systems indicates that some common mechanisms of vesicular movement are used in transport between a variety of membrane compartments. PMID- 1901604 TI - Glucose metabolism in the trophectoderm and inner cell mass of the rabbit embryo. AB - The metabolism of glucose in the intact Day-6 and -7 post coitum (p.c.) rabbit blastocyst and in the separated trophectoderm and inner cell mass (ICM) of the Day-7 p.c. embryo was investigated. At Day-6 p.c., glucose traversed the trophectoderm with a half-time of 39 +/- 9.3 min, and was metabolized to CO2 at a rate of 25.5 +/- 1.6 nmol.cm-2.h-1. Neither the Na+ ionophore, amphotericin B, nor cyclic AMP had an effect on glucose metabolism to CO2. Lactate production by the Day-6 blastocyst was largely independent of glucose. At Day-7 p.c. in the intact embryo, CO2 production from glucose significantly decreased to 7.76 +/- 2.8 nmol.cm-2.h-1. Per unit surface area, the metabolism of glucose to CO2 was similar in the separated Day-7 p.c. trophectoderm and ICM. We conclude that the rabbit blastocyst is not highly dependent on glucose, and that the ICM does not utilize glucose as a metabolite to a greater extent than does the trophectoderm, at least in the Day-7 p.c. embryo. PMID- 1901605 TI - Effect of FSH on ovarian inhibin secretion in anoestrous ewes. AB - In Exp. 1, 7 Finn-Merino ewes which had one ovary autotransplanted to a site in the neck had jugular and timed ovarian venous blood samples collected at 10-min intervals for 2 h before and 3 h after injection of 5 micrograms NIAMDD-oFSH-S16. In Exp. 2, 8 Finn-Merino ewes with ovarian autotransplants had jugular and timed ovarian venous blood samples collected at 15-min intervals for 2 h before and 12 h after bolus injection of 40 micrograms NIAMDD-oFSH-S16 and infusion of oFSH-S16 at 6 micrograms/min for 4 h. In Exp. 2 the follicular population of the ovary was assessed by real-time ultrasound at the beginning and end of the experimental period. In both experiments the secretion rates of inhibin (1-3 ng/min) and oestradiol (0.5-8 ng/min) were similar to those observed during the luteal phase of the cycle in the breeding season, indicating significant follicular development in these animals. In Exp. 1 there was no change in the secretion of oestradiol or inhibin after the injection of FSH which resulted in a 25% increase (P less than 0.05) in the concentration of FSH in plasma. Inhibin secretion was pulsatile but there was no difference in inhibin pulse frequency before (1.6 +/- 0.2 pulses/h) or after (1.2 +/- 0.5 pulses/h) injection of FSH. In Exp. 2 injection of FSH resulted in an increase (P less than 0.001) in plasma concentrations of FSH in the sample taken 10 min after injection from a baseline of 1.2 +/- 0.2 ng/ml to a peak of 10.6 +/- 1.0 ng/ml (mean +/- s.e.m.).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1901606 TI - GnRH-induced gonadotrophin secretion in ovariectomized Booroola ewes with hypothalamic-pituitary disconnection. AB - To test whether the F gene-specific differences in the plasma concentrations of FSH and LH are due to differences in the pituitary responsiveness to exogenous GnRH, ovariectomized Booroola ewes with hypothalamic-pituitary disconnection (HPD ovx) were treated with GnRH (250 ng i.v.) once every 2 h for up to 5 weeks. In Exp. 1, jugular venous blood was collected once weekly from 13 FF and 14 ++ HPD ovx ewes for 6 weeks before GnRH treatment and every 2nd, 3rd or 6th day for 5 weeks during treatment. In Exp. 2, jugular venous blood was collected from another 8 FF and 7 ++ HPD-ovx ewes at 5- or 10-min intervals over 4 GnRH pulses (250 ng i.v. once every 2 h) on 3 separate occasions after the animals had been subjected to the GnRH pulse regimen for approximately 7 days beforehand. Also in Exp. 2, the animals were extensively sampled around a larger (10 micrograms) i.v. injection of GnRH and the pituitary FSH and LH contents assessed after the animals had been re-exposed to the once every 2 h GnRH (250 ng i.v.) pulse regimen for several days following the larger GnRH bolus. In Exp. 3 the distributions of mean plasma concentrations of FSH and LH in individual GnRH treated HPD-ovx ewes were compared with those in ovariectomized and ovary-intact FF and ++ ewes. During the 6 weeks before GnRH treatment (Exp. 1), the plasma concentrations of FSH (approximately 1 ng/ml) and LH (less than or equal to 0.8 ng/ml) were not different between the genotypes. After GnRH treatment both the mean FSH and LH concentrations increased significantly (P less than 0.01) above basal values after 2 days with F gene-specific differences being noted for FSH but not LH (FSH; FF greater than ++; P less than 0.05). Thereafter, the mean FSH but not LH concentrations increased at a faster rate in FF than in ++ ewes with the overall mean FSH concentrations between the genotypes being significantly different (P less than 0.05). In Exp. 2 considerable between-animal variation in the pulsatile pattern of FSH but not LH concentrations was seen in ewes of both genotypes during GnRH treatment. The overall mean FSH concentrations were higher in FF than in ++ ewes (P less than 0.05) and the mean FSH response to each GnRH pulse was significantly higher in FF than in ++ ewes (P less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1901607 TI - Increased ovulation rate in androstenedione-immune ewes is not due to elevated plasma concentrations of FSH. AB - Two experiments were undertaken to determine the hormonal response of Merino ewes to immunization against androstenedione (Fecundin). In Exp. 1 peripheral concentrations of LH, FSH and progesterone were monitored in spontaneously cycling ewes (20 immunized and 21 controls). In Exp. 2 (10 immunized and 10 controls) the same hormones were measured in ewes before and after prostaglandin (PG)-induced luteolysis and, in addition, the pattern of pulsatile LH secretion was determined during the luteal (PG + 12 days), early follicular (PG + 24 h) and late follicular (PG + 40 h) phase of the oestrous cycle. Ovulation rates were measured in both experiments. The results of these experiments indicate that androstenedione-immune animals have elevated ovulation rates (0.6-0.7 greater than control animals; P less than 0.05) associated with elevated plasma concentrations of LH and progesterone. The magnitude of the increase in plasma progesterone was correlated with androstenedione antibody titre (r = 0.6, P less than 0.001). LH pulse frequency of androstenedione-immune ewes tended to be higher at all stages of the oestrous cycle, but this difference was only significant (P less than 0.05) during the luteal phase. Mean plasma concentrations of FSH did not differ significantly between immunized and control ewes at any stage of the cycle. Analysis of periodic fluctuations in FSH during the luteal phase revealed that androstenedione-immune animals had a similar number of fluctuations of a similar amplitude to those of control animals, but the nadir of these fluctuations was lower (P less than 0.05) in immunized animals. A significant (P less than 0.05) negative correlation existed between androstenedione antibody titre and the interval between FSH peaks (r = -0.49) and androstenedione antibody titre and FSH nadir concentrations (r = -0.46). It is concluded that plasma FSH concentrations are not a determinant of ovulation rate in androstenedione-immune ewes and that increased LH concentrations, or perturbation of normal intraovarian mechanisms, may be responsible for the increase in ovulation rate observed in ewes immunized against androstenedione. PMID- 1901608 TI - Long-term parenteral nutrition: problems with venous access. PMID- 1901609 TI - Drug abuse in the United States. Strategies for prevention. AB - Efforts to curtail abuse of alcohol and other drugs concentrate on activities designed for supply-and-demand reduction. Many law enforcement and health officials agree that the reduction in supply of drugs cannot succeed as long as the demand for drugs for purposes of abuse occurs in a significant segment of society. Critical to reducing this demand is prevention. Only through an understanding of the correlates and risk factors associated with the use of alcohol and other drugs, along with the identification and implementation of sound strategies, can change occur. Although research has uncovered a considerable body of knowledge about the interplay of personal behavior, risk factors, and health in the prevention of substance abuse, many questions remain unanswered. Until those answers are known, efforts that have proven most effective need to be more widely emphasized. PMID- 1901610 TI - Setting health care priorities in Oregon. Cost-effectiveness meets the rule of rescue. AB - The Oregon Health Services Commission recently completed work on its principal charge: creation of a prioritized list of health care services, ranging from the most important to the least important. Oregon's draft priority list was criticized because it seemed to favor minor treatments over lifesaving ones. This reaction reflects a fundamental and irreconcilable conflict between cost effectiveness analysis and the powerful human proclivity to rescue endangered life: the "Rule of Rescue." Oregon's final priority list was generated without reference to costs and is, therefore, more intuitively sensible than the initial list. However, the utility of the final list is limited by its lack of specificity with regard to conditions and treatments. An alternative approach for setting health care priorities would circumvent the Rule of Rescue by carefully defining necessary indications for treatment. Such an approach might be applied to Oregon's final list in order to achieve better specificity. PMID- 1901611 TI - Diminishing returns on the road to diagnostic certainty. AB - In the quest for diagnostic certainty, one can be led into a false sense of accomplishment by the results of sensitive, specific, and well-executed diagnostic tests that provide little or no diagnostic information. This is a consequence of the fact that as one approaches diagnostic certainty the useful information returned by diagnostic tests and observations approaches zero. This can be demonstrated by calculating the quantity of useful information provided by a test in a given clinical environment as one approaches certainty of diagnosis. PMID- 1901612 TI - Oregon's bold Medicaid initiative. PMID- 1901613 TI - [In vitro experiment showing that chemotherapy of tuberculosis by aminoglycoside antibiotics may influence successive chemotherapy with rifampicin]. AB - When Mycobacterium tuberculosis strain H37Rv was cultivated in Ogawa egg medium containing 5 micrograms/ml streptomycin and/or 10 micrograms/ml kanamycin, which were considered as subinhibitory, it was observed that growing bacterial population contained several times more rifampicin-resistant mutants than did the parent strain. The ratio of isoniazid-resistant mutants did not change by the above treatment. The finding suggests that, even without the use of rifampicin, the bacterial population of patients becomes more resistant to rifampicin by chemotherapy in the past with streptomycin or kanamycin. Furthermore, it was shown that the ratio of streptomycin-resistant mutants increased by pre-treatment with kanamycin and the ratio of kanamycin-resistant mutants by pre-treatment with streptomycin. Parent, susceptible bacterial population develops 4R-phenotype mutants which are resistant to four drugs, high concentrations of kanamycin, lividomycin and paraomomycin and a low concentration of capreomycin, whereas streptomycin-resistant mutant population does not develop the 4R mutants but develops only mutants with the KR phenotype which is almost mono-resistant to kanamycin. PMID- 1901615 TI - The regulation of genetic competence in Bacillus subtilis. AB - Genetic competence develops as a global response of Bacillus subtilis to the onset of stationary phase, in glucose-minimal salts-based media. The onset of competence is accompanied by the expression of several late gene products that are required for the binding, processing and uptake of transforming DNA. A number of regulatory genes have been identified that are needed for the appropriate synthesis of the late gene products. The regulatory gene products include a number of known transcription factors, as well as several members of the bacterial two-component regulatory system. Genetic analysis has suggested a scheme for the flow of regulatory information signalling the onset of competence. Most of these regulatory products appear to be involved in the response to nutritional status, while the components responsible for growth stage and cell type-specific control remain unknown. The general implications of this scheme for post-exponential expression are discussed. PMID- 1901614 TI - Serum CD4, CD8, and interleukin-2 receptor levels in childhood acute myeloid leukemia. AB - Leukemic cell expression and serum levels of CD4, CD8, and interleukin-2 receptor (IL-2R) were determined at diagnosis for children or adolescents with acute myeloid leukemia (AML). Cellular expression of CD4 was detected in 18 of 62 cases, CD8 in none of 60 cases, and IL-2R in one of 33 cases tested. Myeloblasts of the M4 and M5 subtypes expressed CD4 significantly more frequently than other FAB subtypes (p = 0.0001). Serum levels of the three soluble factors (tested for 91 patients) were positively correlated with each other. Increased serum CD4 levels were significantly associated with cellular CD4 expression, high leukocyte count, M5 leukemia, spleen enlargement, and age less than 1 year. High serum CD8 levels correlated significantly with splenomegaly, extramedullary disease, absence of Auer rods, and high leukocyte count. Cases with high serum IL-2R levels were less likely to have Auer rods and more likely to have splenomegaly and M5 leukemia; serum levels greater than 750 U/ml were associated with a higher probability of treatment failure (p = 0.05), even after adjustment for other potential prognostic factors. Further studies of serum CD4, CD8, and IL-2R levels may help to clarify the immunoregulatory role of T-cells in patients with AML. PMID- 1901616 TI - The oligopeptide transport system of Bacillus subtilis plays a role in the initiation of sporulation. AB - Bacillus subtilis spo0K mutants are blocked at the first step in sporulation. The spo0K strain was found to contain two mutations: one was linked to the trpS locus, and the other was elsewhere on the chromosome. The mutation linked to trpS was responsible for the sporulation defect (spo-). The unlinked mutation enhanced this sporulation deficiency but had no phenotype on its own. The spo- mutation was located in an operon of five genes highly homologous to the oligopeptide transport (Opp) system of Gram-negative species. Studies with toxic peptide analogues showed that this operon does indeed encode a peptide-transport system. However, unlike the Opp system of Salmonella typhimurium, one of the two ATP binding proteins, OppF, was not required for peptide transport or for sporulation. The OppA peptide-binding protein, which is periplasmically located in Gram-negative species, has a signal sequence characteristic of lipoproteins with an amino-terminal lipo-amino acid anchor. Cellular location studies revealed that OppA was associated with the cell during exponential growth, but was released into the medium in stationary phase. A major role of the Opp system in Gram-negative bacteria is the recycling of cell-wall peptides as they are released from the growing peptidoglycan. We postulate that the accumulation of such peptides may play a signalling role in the initiation of sporulation, and that the sporulation defect in opp mutants results from an inability to transport these peptides. PMID- 1901617 TI - Computer modelling of the NAD binding site of ADP-ribosylating toxins: active site structure and mechanism of NAD binding. AB - Five ADP-ribosylating bacterial toxins, pertussis toxin, cholera toxin, diphtheria toxin, Escherichia LT toxin and Pseudomonas exotoxin A, show significant homology in selected segments of their sequence. Site-directed mutagenesis and chemical modification of residues within these regions cause loss of catalytic activity and of NAD binding. On the basis of these results and of molecular modelling based on the three-dimensional structure of exotoxin A, the geometry of an NAD binding site common to all the toxins is deduced and described in the paper. For diphtheria toxin, sequence similarity with exotoxin A is such that its preliminary structure can be computed by molecular modelling, whereas for the other toxins similarity appears to be restricted to the NAD binding site. Moreover, an analysis of molecular fitting of the NAD molecule into its binding cavity suggests a new model for the conformation of the bound NAD that better accounts for all available experimental information. PMID- 1901619 TI - Increasing breast cancer screening among the medically underserved--Dade County, Florida, September 1987-March 1991. AB - Efforts to detect breast cancer at early stages are critical in reducing breast cancer-associated mortality. However, in the United States, different barriers (e.g., lack of insurance, limited access to medical care, and limited awareness of the importance of early diagnosis and treatment) prevent certain groups from using early detection services. To promote early detection of breast cancer among an estimated 67,000 medically underserved women aged greater than or equal to 40 years, the Early Detection Program (EDP) was begun in Dade County, Florida, in the fall of 1987 (1). This report summarizes the progress of the program for September 1987 through March 1991.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1901620 TI - Outbreaks of rubella among the Amish--United States, 1991. AB - From January 1 through April 19, 1991, at least nine outbreaks of rubella, involving more than 400 cases, have been reported in Amish communities in the United States. These outbreaks have been reported from Mecosta and Montcalm counties, Michigan; Allegany, Cattaraugus, Chautauqua, and St. Lawrence counties, New York; Geauga, Knox, and Trumbull counties, Ohio; and Lawrence County, Tennessee. In addition, serologically confirmed cases of rubella have been reported from Amish communities in six Pennsylvania counties, suggesting widespread rubella activity among the Amish in Pennsylvania. In general, cases have occurred among unvaccinated children and young adults.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1901618 TI - Influence of divalent ions on the solubility of iturin and bacillomycin L, antifungal peptidolipids of Bacillus subtilis. AB - When calcium chloride was added to the culture medium of strains producing iturin or bacillomycin L, the antibiotic, normally excreted in the supernatant of the culture medium, was found in the cell pellet. This apparent inhibition of the antibiotic excretion was studied and it was demonstrated that CaCl2 precipitated the antibiotic after its excretion in the medium. The ability of various chloride salts to precipitate iturin and bacillomycin L was tested and the most effective salts were CaCl2 and MnCl2. Comparison of the compounds obtained by CaCl2 precipitation and by acid precipitation showed that, in the latter case, major antibiotics were accompanied by minor congeners resulting from modifications of genuine antibiotics. PMID- 1901621 TI - Foodborne outbreak of gastroenteritis caused by Escherichia coli O157:H7--North Dakota, 1990. AB - In late July and early August 1990, an outbreak of gastroenteritis occurred among persons who had eaten a meal while attending an agricultural threshing show in North Dakota on July 28-29. At least 70 (3.5%) of the more than 2000 attendees were affected; of these, 16 persons were hospitalized, and two children, aged 2 and 8 years, were diagnosed with hemolytic uremic syndrome. An epidemiologic investigation was conducted by the North Dakota State Department of Health and Consolidated Laboratories.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1901622 TI - [Significance of changes in plasma arginine level after surgery on hemodialysis patients: preliminary report]. PMID- 1901623 TI - The deteriorating administrative efficiency of the U.S. health care system. AB - BACKGROUND AND METHODS: In 1983 the proportion of health care expenditures consumed by administration in the United States was 60 percent higher than in Canada and 97 percent higher than in Britain. To assess the effects of recent health policy initiatives on the administrative efficiency of health care, we examined four components of administrative costs in the United States and Canada for 1987: insurance overhead, hospital administration, nursing home administration, and physicians' billing and overhead expenses. Most data were provided by the two nations' federal health and statistics agencies, supplemented by state and provincial data and published sources. Because data on physicians' billing costs were limited, we estimated a range for these costs by two methods that rely on different sources of data. All figures are reported in 1987 U.S. dollars. RESULTS: In 1987 health care administration cost between $96.8 billion and $120.4 billion in the United States, amounting to 19.3 to 24.1 percent of total spending on health care, or $400 to $497 per capita. In Canada, between 8.4 and 11.1 percent of health care spending ($117 to $156 per capita) was devoted to administration. Administrative costs in the United States increased 37 percent in real dollars between 1983 and 1987, whereas in Canada they declined. The proportion of health care spending consumed by administration is now at least 117 percent higher in the United States than in Canada and accounts for about half the total difference in health care spending between the two nations. If health care administration in the United States had been as efficient as in Canada, $69.0 billion to $83.2 billion would have been saved in 1987. CONCLUSIONS: The administrative structure of the U.S. health care system is increasingly inefficient as compared with that of Canada's national health program. Recent health policies with the avowed goal of improving the efficiency of care have imposed substantial new bureaucratic costs and burdens. PMID- 1901624 TI - Lisch nodules in neurofibromatosis type 1. PMID- 1901625 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 18-1991. A 70-year-old man with Waldenstrom's macroglobulinemia followed by recurrent lymphadenopathy and fever. PMID- 1901626 TI - Neurofibromatosis: past, present, and future. PMID- 1901627 TI - Metabolism of aflatoxin B1 by Petroselinum crispum (parsley). AB - On administration of aflatoxin B1 to whole parsley (Petroselinum crispum) plants, a derivative was formed, which was shown to be aflatoxicol by its chromatographic properties and mass spectrometry. Optimum conditions for the production of the derivative was on the second day after administration of the toxin to the plants, which were 90 days old after germination. Cell-free preparations of parsley were found not to produce aflatoxicol A from added aflatoxin B1; instead they formed two new derivatives, which from chromatographic properties, were shown to be more polar than either aflatoxin B1 or aflatoxicol A. PMID- 1901628 TI - The molten globule protein conformation probed by disulphide bonds. AB - The molten globule is a compact protein conformation that has a secondary structure content like that of the native protein, but poorly defined tertiary structure. It is a stable state for a few proteins under particular conditions and could be a ubiquitous kinetic intermediate in protein folding. The extent to which native interactions, above the level of the secondary structure, are preserved in this conformation is not so far known. Here we report that alpha lactalbumin can adopt a molten globule conformation when one of its four disulphide bonds is reduced. In this state, the three other disulphide bonds rearrange spontaneously, at the same rate as when the protein is fully unfolded, to a number of different disulphide bond isomers that tend to maintain the molten globule conformation. That the molten globule state is compatible with a variety of disulphide bond pairings suggests that it is unlikely to be stabilized by many specific tertiary interactions. PMID- 1901629 TI - [Desmopressin in hemophilia A and Von Willebrand's disease]. AB - The treatment with desmopressin prior to surgery of patients with mild haemophilia A (HA) and Von Willebrand's disease (VWD) was retrospectively evaluated in a general hospital, from 1978 until 1987. From a group of 87 treated patients, 40 patients are reported (21 VWD, 19 HA) of which plasma factor VIII (FVIII) and Von Willebrand factor (VWF) concentrations were determined before, and twice after desmopressin treatment. Desmopressin was administered intravenously at a dose of 0.4 micrograms/kg body weight. Tranexamic acid was used only when surgery in the mouth cavity was performed, at a dose of 1 gram three times a day. Side effects were seen only in 5 patients (3 VWD, 2 HA). No significant difference between both groups was seen in bleeding tendency, transfusion necessity and side effects (chi 2 test). In both groups, FVIII and VWF concentrations increased significantly after 20 and 60 minutes following DDAVP administration (paired t-test). After 360 minutes, the FVIII concentration increased significantly in both groups, however, only in the VWD patients did VWF increase significantly. In neither group did initial FVIII concentrations correlate with the increase in FVIII (linear regression analysis). One female patient reacted differently to DDAVP, with a decrease in FVIII and VWF values. Desmopressin is a safe and effective agent in the management and prophylaxis of bleeding tendency in patients with mild HA and mild VWD. PMID- 1901630 TI - Involvement of catecholaminergic systems in the zona incerta in the steroidal control of gonadotrophin release and female sexual behaviour. AB - Previous reports have shown that dopamine (DA) in the zona incerta (ZI) has a stimulatory effect on gonadotrophin release. We have now investigated the possibility that steroids exert their feedback effects on the release of luteinizing hormone (LH) via catecholamine systems in the ZI. Since the same steroid regimes also stimulate female sexual behaviour, the possibility that the ZI is also involved in the control of sexual activity was investigated. Lesions in the ZI increased proceptive and receptive behaviour in oestrogen-primed ovariectomised rats that exhibited a low level of lordosis in a pre-lesion test and had no effect in receptive animals. Turnover rates (TR) of DA, noradrenaline (NA) and adrenaline were measured in the ZI, preoptic area (POA), arcuate nucleus (ARC), median eminence (ME) and ventromedial nucleus in ovariectomised rats treated 54 h before with either oil, oestradiol benzoate (OB) at 5, 10 or 50 micrograms/rat, or 5 micrograms/rat OB followed by 0.5 mg/rat progesterone (P) 48 h later. The TR as measured from the decline in concentration after alpha methyltyrosine and changes in DOPAC concentration were correlated with the effect of the steroids on plasma LH and lordotic activity. Confirming previous reports, NA turnover in the POA and ME was increased, and DA turnover in the ME was decreased by steroids when they enhanced LH release. DA turnover in the ARC and ME was reduced when lordosis behaviour increased. Treatment with OB plus P stimulated LH release and sexual receptivity and at the same time significantly increased DA and NA turnover in the ZI. There was no correlation between these parameters after OB alone. This report shows that the DA system in the ZI may mediate the stimulatory effect of P on LH release in OB-primed rats but is not involved in the feedback effects of oestradiol alone. NA activity in the ZI is increased after OB plus P and may therefore also be concerned with stimulating LH release. The ZI is involved in the control of sexual behaviour, as electrolytic lesions in this area enhance receptivity and proceptivity, but the catecholamine systems in the ZI do not appear to mediate this control. PMID- 1901631 TI - Basal luteinizing hormone and follicle-stimulating hormone release rates as a function of time after castration in female and male rats. AB - We investigated the potential importance of the basal follicle-stimulating hormone (FSH) and luteinizing hormone (LH) release rates in causing the acute and chronic elevations in serum FSH and LH concentrations which occur after ovariectomy (OVX) and orchidectomy (ORCH) of rats. Diestrous day 1 female and male rats were decapitated or castrated and killed 2, 4 or 8 h or 1, 2, 7, 21 or 35 days later. In females, the weight of the anterior pituitary gland (APG) did not change. Serum FSH rose within 4 h and then progressively higher until 35 days after OVX. These increases were paralleled nearly perfectly with increases in APG FSH concentration which was first elevated at 1 day after OVX and in the basal FSH release rate (measured in vitro) which was first elevated at 4 h after OVX. Serum LH levels rose by 7 days after OVX and then more dramatically thereafter. These increases were associated with increased APG LH concentrations. The pronounced increases in serum LH levels between 7 and 35 days after OVX were associated with marked increases in the basal LH release rate. In males, APG weight was increased at 21 and 35 days after ORCH. Serum FSH levels were elevated at 1 day after ORCH and continued to rise until 21 days after ORCH. APG FSH concentration was decreased at 2 and 7 days and increased at 35 days after ORCH. The basal FSH release rate per milligram APG did not change significantly after ORCH. Serum LH levels were elevated at 8 h after ORCH. They rose further by 1 day and then further between 7 and 21 days after ORCH. APG LH concentration and the basal LH release rate per milligram APG were elevated at 21 and 35 days after ORCH. The results suggest that changes in basal FSH and LH release are (1) involved to a major extent in causing the post-OVX rise in serum FSH concentration during the first 5 weeks after OVX and in serum LH concentration between 7 and 35 days after OVX, (2) not involved in causing the post-ORCH rises in serum FSH and LH concentrations during the 1 week after ORCH, and (3) involved to some extent in causing the elevations in serum FSH and LH concentrations observed at 3 and 5 weeks after ORCH. The results also indicate that (1) increases in the basal gonadotropin release rates per milligram APG after castration may be coupled in some way with increased synthesis of gonadotropin, and (2) increases in the basal LH release rate per milligram APG can occur independently of an increase in the basal FSH release rate per milligram APG. PMID- 1901632 TI - Evidence for entrainment of nocturnal cortisol secretion to sleep processes in human beings. AB - The pulsatile patterns of cortisol release have been referred to as 'episodic' rather than 'rhythmic'. We studied plasma cortisol patterns in 31 healthy subjects during night sleep and observed a uniform ultradian rhythm. Using spectral analysis a predominant mean periodicity of 151.2 +/- 8.3 min (mean +/- SEM) was calculated for plasma cortisol oscillations, and of 118.3 +/- 4.3 min for REM sleep occurrence. The rhythmic pattern of plasma cortisol was obscured when data were averaged across subjects, due to the individual onset latencies of the initial cortisol rise. Therefore, the data were analyzed time-locked to a number of somnopolygraphic sleep events: by selecting the end of the second sleep cycle as point of reference, the ultradian rhythm was preserved. These results indicate that both sleep processes and nocturnal plasma cortisol concentrations are subject to ultradian rhythms. Both rhythms are coupled, but have different periodicities. PMID- 1901633 TI - Variable distribution, in four rat brain areas, of the three natural forms of peptide histidine isoleucinamide: PHI(1-27)NH2, PHI-Gly, and PHV (1-42). AB - Three parent peptides were shown to coexist in four rat brain regions: PHI(1 27)NH2 (peptide with an N-terminal histidine and a C-terminal isoleucinamide commonly called PHI), PHI-Gly (PHI(1-27)Gly) and PHV(1-42) (a 42 amino acids form with a C-terminal valine, consisting of PHI(1-27) C-terminally extended by the connecting peptide between PHI and VIP in the precursor molecule except for the terminal basic doublet preceding VIP). A differential distribution of the 3 forms was observed by means of radioimmunoassay, after chromatographic separation on Fractogel, in extracts from temporal cortex, hippocampus, striatum and hypothalamus. Total PHI-IR concentration was found to be higher in the temporal cortex and hippocampus than in the striatum and hypothalamus. PHI(1-27)NH2 was the major form, and accounted for 55% of total PHI-IR in the cortex and hippocampus, 62% in the hypothalamus and as much as 70% in the striatum. PHI-Gly represented 18% of total PHI-IR in the cortex and hippocampus, and 11% in the two other brain areas. PHV(1-42) represented 26% of total PHI-IR in all areas except in the striatum where it represented 18% only. PMID- 1901634 TI - Brain aromatization of testosterone in the male Syrian hamster: effects of androgen and photoperiod. AB - Estrogen formed by aromatization of testosterone (T) is involved in the activation of sexual behavior and control of the neuroendocrine system in the male Syrian hamster. Our study examined whether daylength influences formation of estrogen in the preoptic area (POA) and other neuroendocrine areas (anterior hypothalamus, AHT, and medial amygdala, MA) which are targets for T in behaviorally active males. Estrogen formation in individual brain samples was assayed in vitro using the stereospecific production of 3H2O from (1 beta-3H) T as a measurement of aromatase activity. Serum levels of PRL, LH, FSH and T were compared with brain aromatase activity. Groups of intact, castrated and T-treated (chronic silastic T implants) male hamsters, previously selected on behavioral criteria as being sexually active, were maintained on long (16:8LD) or short (8:16LD) daylength for 16 weeks. Two further groups of males either intact or castrated and T-treated were shifted after 7 weeks from the long photoperiod to 12:12LD. POA, AHT and MA areas of sexually active males contained active aromatase systems which converted 3H-T to estrogens. Enzyme activity differed between the areas (POA, MA greater than AHT). Aromatase activity was low in medial septum and cerebral samples. Castration, which reduced serum T to undetectable levels and elevated LH and FSH, had no effect on preoptic aromatase activity. Although estrogen formation in POA did not differ between 8:16LD and 16:8LD males, castration reduced aromatase activity in AHT of both short- and long-day groups. Aromatase activity in AHT was also significantly reduced in photo-inhibited 12:12LD intact males. There was no analogous decrease in 5 alpha reductase or 17 beta-hydroxysteroid dehydrogenase (HSD) activity, indicating a specific effect on the aromatase. The effect of photoperiod on aromatase activity was not reversed by T treatment. Therefore, photoinhibition acts in part through the effects of reduced T levels on the anterior hypothalamus, but it also acts independently of circulating T. Our results suggest that both androgen and photoperiod may regulate the AHT aromatase system and that this occurs by different mechanisms. The more active aromatase system in POA is insensitive to both castration and photoperiod. Behavioral deficits in short-day males are not due to changes in the preoptic aromatase system, but may be related to changes in aromatase activity within AHT. We conclude that there is a difference in the regulation of two locally active aromatase systems within the preoptic-anterior hypothalamic complex of the male hamster. PMID- 1901635 TI - Stimulatory effect of angiotensin II upon luteinizing hormone release normal women. AB - In this study we investigated the effect of intravenous infusion of angiotensin II (AII) on plasma luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels in fertile healthy women examined both in the middle follicular phase (MFP) and in the middle luteal phase (MLP). As expected, AII induced a significant increase in blood pressure and plasma aldosterone concentration. In MFP, plasma FSH and LH levels did not show any significant change after AII infusion, if compared to both saline and preinfusion basal values. In MLP, AII significantly increased plasma LH (p less than 0.02 vs. baseline values and p less than 0.01 vs. placebo values), but not plasma FSH. The area under the curve during AII infusion resulted significantly higher than during placebo infusion (p less than 0.001). Therefore, these data demonstrate that peripherally injected AII at pressive dose produces an increase in plasma LH levels in normal women on luteal phase when the circulating concentrations of both estradiol and progesterone are high. The study suggests that AII may have a stimulatory role in the regulation of LH secretion, but this role is closely related to the gonadal steroid plasma levels. PMID- 1901636 TI - Aluminum-induced chronic myelopathy in rabbits. AB - Young adult New Zealand white rabbits, inoculated intracisternally once monthly with 100 micrograms AlCl3, developed progressive hyperreflexia, hypertonia, gait impairment, weight loss, muscle wasting and abnormal righting reflexes over the course of 8 months. No overt encephalopathic features were present. In spinal motor neuron perikarya, dendrites and axonal processes, argentophilic globular inclusions were extensive. Additionally, neurofibrillary tangle-like argentophilic inclusions were consistently present in the gigantocellularis, reticularis, raphe and trapezoid nuclei, but rarely present in the dorsal and ventral subiculum, parasubiculum and anterior thalamus, and never found in the cerebral cortex, substantia nigra, locus ceruleus, or cerebellum. All neuronal inclusions were immunoreactive with monoclonal antibodies recognizing phosphorylated and nonphosphorylated high and intermediate weight neurofilament proteins (SMI 31, SMI 32). Also, some spinal motor neuron inclusions were immunoreactive with a monoclonal antibody recognizing an 'age-related' phosphorylation state of neurofilament (SMI 34). Ultrastructurally, the inclusions consisted of straight or interwoven skeins of 10 nm filaments. This study demonstrates unique variability in the phosphorylation state of aluminum induced neurofilamentous inclusions in a predominantly motor system degeneration induced by chronic low dose AlCl3. PMID- 1901637 TI - Thyroid function in small for gestational age fetuses. AB - Thyroid function was studied in fetal blood samples obtained by funipuncture from 49 small for gestational age (SGA) fetuses at 21-38 weeks' gestation. Levels of TSH, thyroxine-binding globulin, thyroxine (T4), free T4, triiodothyronine (T3), and free T3 were compared with those from 62 appropriate for gestational age (AGA) fetuses. Levels of TSH were significantly higher and T4 and free T4 significantly lower in the SGA than in AGA fetuses. Furthermore, there were significant associations between the increase in TSH and decrease in free T4 and the degrees of fetal hypoxemia and acidemia, respectively. PMID- 1901638 TI - Treatment of leiomyomata uteri with leuprolide acetate depot: a double-blind, placebo-controlled, multicenter study. The Leuprolide Study Group. AB - The purpose of this study was to evaluate efficacy and safety parameters in women with leiomyomata uteri treated with the GnRH agonist leuprolide acetate depot, 3.75 mg intramuscularly every 4 weeks for 24 weeks. One hundred twenty-eight patients were enrolled in a randomized, double-blind, placebo-controlled multicenter study involving 13 investigative centers. Mean uterine volume decreased by 36% at 12 weeks and 45% at 24 weeks of leuprolide therapy. Patients treated with placebo had increased in mean uterine volume of 16% at 12 weeks and 5% at 24 weeks. Seventy-seven percent of leuprolide-treated patients had a more than 25% reduction in uterine volume, compared with 9% of placebo-treated controls. Mean uterine volume returned to pre-treatment size 24 weeks after cessation of leuprolide treatment. The majority of patients had resolution or improvement of their fibroid-related symptoms after 24 weeks of leuprolide treatment. Of 38 leuprolide-treated patients presenting with menorrhagia, 37 (97%) had resolution of this symptom at the time of the final visit. Although 95% of women treated with leuprolide acetate experienced some side effects related to hypoestrogenism, only five patients (8%) terminated treatment prematurely. We conclude that leuprolide acetate depot treatment of leiomyomata uteri is safe and causes significant but temporary reductions in uterine size and fibroid-related symptoms. PMID- 1901639 TI - Transfer from ophthalmology to another service is a marker of high risk medical events. AB - Of 3632 consecutive admissions to the Wilmer Ophthalmological Institute between July 1, 1987 and June 30, 1989, 27 patients required transfer to a medical or surgical service (0.74%). The major reasons for transfer included acute or decompensated cardiac disease (26%), poorly controlled diabetes mellitus (19%), acute renal failure (11%), coagulopathy, stroke, and hypertension (7% each). Only one transfer was a direct result of an anesthesia complication. The highest rates of transfers were associated with orbital (4.3%), enucleation/evisceration (3.1%), and glaucoma (2.3%) surgeries, while vitreoretinal surgery had the lowest rate of transfer (0.3%). Most of the transfers of patients with orbital disease were for management of related problems such as sinusitis or increased intracranial pressure. PMID- 1901640 TI - Characterization of a polymorphic immunodominant molecule in sporozoites and schizonts of Theileria parva. AB - This study examines several aspects of a polymorphic, immunodominant molecule (PIM) found in the protozoan parasite, Theileria parva. The antigen is present in all T.p. parva stocks examined, and in the related subspecies, T.p.bovis and T.p.lawrencei. It is the predominant antigen recognized by antisera from immune cattle on Western blot analysis of schizont-infected lymphocytes, and is the only antigen which has been shown to react with anti-schizont monoclonal antibodies (MoAbs) on Western blots or in immunoprecipitations. The antigen shows polymorphism in both size and expression of antibody epitopes among the different stocks of T. parva. The antigen is present in sporozoites as well as schizonts. PMID- 1901641 TI - Interferon-gamma-mediated effects upon immunity to coccidial infections in the mouse. AB - The effect of treatment with a monoclonal antibody (MoAb) capable of neutralising interferon-gamma (IFN-gamma) on the course of coccidial infections in mice (C57BL/6 and NIH infected with Eimeria vermiformis or E. pragensis, and BALB/c infected with E. pragensis) was examined. The results differed with the species of parasite, the strain of mouse, the measure of infection and whether the infection was a primary or secondary one. The replication of E. vermiformis in primary infections was enhanced in both C57BL/6 and NIH mice, but less MoAb was required in NIH than in C57BL/6 to produce similar effects. In neither strain did treatment prevent priming or interfere with the complete immunity to challenge normally induced by moderate infection with E. vermiformis. The replication of E. pragensis in primary infections was not affected in any of the strains of mouse but the clinical effects were exacerbated. Priming with E. pragensis was unaffected by treatment but the partial immunity to challenge, normally induced by infection with this species, was reduced when MoAb was given 2 h before challenge. This reduction was evident as an increased faecal output of oocysts and loss of body weight. These results confirm the role of IFN-gamma in resistance to coccidiosis and further emphasise the complexity of the immune response in this disease. PMID- 1901642 TI - Age-related change of pulsatile gonadotropin secretion in Turner syndrome. AB - In an attempt to understand the dynamic change of the gonadotropin-releasing hormone-pituitary axis during the transitional stage from prepuberty to puberty, we investigated gonadotropin secretory patterns using a highly sensitive assay system and frequent blood sampling technique in children with Turner syndrome aged 5-17 y. Blood samples were collected every 20 min for 24 h in 16 cases, or every 30 min for 9 h (daytime 5 h, nighttime 4 h) in nine cases. Serum LH and FSH were measured by time-resolved fluoroimmunoassay. A 24-h profile of LH and FSH was analyzed by a computerized pulse detection program (PC-PULSAR). As early as 5 to 6 y of age, mean daytime LH concentration was significantly higher than nighttime concentration and pulsatile LH secretion existed throughout the day and night. At about 9 to 11 y of age, corresponding to the early stage of puberty, a dramatic increase in LH concentration and amplitude was observed, and both concentration and pulse amplitude were much higher during the night than during the day. However, these day-night differences became less clear at ages corresponding to late pubertal stages. Pulse frequency of LH secretion remained almost constant throughout the day and night at all ages investigated. As for FSH concentration, a trend similar to that of LH was observed, although day-night differences and age-related changes were less remarkable. Furthermore, pulsatile FSH secretion was detected in only a small number of the cases. These findings suggest that in Turner syndrome the hypothalamic gonadotropin-releasing hormone oscillator is functioning actively with constant frequency before the onset of puberty.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1901644 TI - The yeast DNA ligase gene CDC9 is controlled by six orientation specific upstream activating sequences that respond to cellular proliferation but which alone cannot mediate cell cycle regulation. AB - By fusing the CDC9 structural gene to the PGK upstream sequences and the CDC9 upstream to lacZ, we showed that the cell cycle expression of CDC9 is largely due to transcriptional regulation. To investigate the role of six ATGATT upstream repeats in CDC9 regulation, synthetic copies of the sequence were attached to a heterologous gene. The repeats stimulated transcription strongly and additively, but, unlike conventional yeast UAS elements, only when present in one orientation. Transcription driven by the repeats declines in cells held at START of the cell cycle or in stationary phase, as occurs with CDC9. However, the repeats by themselves cannot impart cell cycle regulation to a heterologous gene. CDC9 may therefore be controlled by an activating system operating through the repeats that is sensitive to cellular proliferation and a separate mechanism that governs the periodic expression in the cell cycle. PMID- 1901643 TI - Interleukin-1 or phorbol induction of the stromelysin promoter requires an element that cooperates with AP-1. AB - Interleukin-1, a mediator of inflammation, or tumor promoting phorbol esters induce transcription of stromelysin, a metalloproteinase that degrades extracellular matrix molecules and that is overexpressed in diseases such as rheumatoid arthritis. Sequences required for induction of transcription of the human stromelysin promoter are contained on a 46 base pair fragment. This fragment contains a sequence with a high degree of similarity to the binding site for the transcription factor activator protein-1 (AP-1) and indeed, the AP-1 sequence of this fragment is necessary but not sufficient for the maximal response to phorbol 12-myristate 13-acetate (phorbol) or interleukin-1. Maximal induction requires functional cooperation between the AP-1 sequence and a neighboring upstream regulatory sequence (URS) of the stromelysin promoter which is also necessary but not sufficient. We demonstrate that both the AP-1 sequence and the URS bind phorbol or interleukin-1 induced nuclear proteins. Cooperation of the AP-1 sequence with another sequence present in the stromelysin promoter may be a general mechanism whereby the AP-1 element, which is found in many promoters, achieves a maximal and specific response to various stimuli. PMID- 1901646 TI - Cloning of a grasshopper cDNA coding for a protein homologous to the A1, A2/B1 proteins of mammalian hnRNP. PMID- 1901645 TI - Sequence effect on incision by (A)BC excinuclease of 4NQO adducts and UV photoproducts. AB - Nucleotide excision repair in Escherichia coli is initiated by (A)BC excinuclease, an enzyme which incises DNA on both sides of bulky adducts and removes the damaged nucleotide as a 12-13 base long oligomer. The incision pattern of the enzyme was examined using DNA modified by 4-nitroquinoline 1-oxide (4NQO) and UV light. Similar to the cleavage pattern of UV photoproducts and other bulky adducts, the enzyme incises the 8th phosphodiester bond 5' and 5th phosphodiester bond 3' to the 4NQO-modifed base, primarily guanine. The extent of DNA damage by these agents was determined using techniques which quantitatively cleave the DNA or stop at the site of the adduct. By comparison of the intensity of gel bands created by (A)BC excinuclease and the specific cleavage at the damaged site, the efficiency of (A)BC excinuclease incision at 13 different 4NQO induced adducts and 13 different photoproducts was determined by densitometric scanning. In general, incisions made at 4NQO-induced adducts are proportional to the extent of damage, though the efficiency of cutting throughout the sequence tested varies from 25 to 75%. Incisions made at pyrimidine dimers are less efficient than at 4NQO-adducts, ranging from 13 to 65% incision relative to modification, though most are around 50%. The two (6-4) photoproducts within the region tested are incised more efficiently than any pyrimidine dimer. PMID- 1901647 TI - Dose-dependent pharmacokinetics of the aldose reductase inhibitor imirestat in man. AB - The pharmacokinetics of imirestat were studied in healthy volunteers following single and multiple oral doses. After single doses of 20 to 50 mg, imirestat plasma concentrations declined with an apparent elimination half-life of 50 to 70 hr over the 168 hr in which levels were measured. However, with lower doses (2 to 10 mg), an initial rapid decline in drug concentration was followed by a very slow terminal elimination phase with plasma concentrations decreasing little over the 1 week of sampling. This resulted in a decrease in apparent t 1/2 with increasing dose, from 272 +/- 138 hr at 2 mg to 66 +/- 30 hr at 50 mg. During once-daily dosing of 2 to 20 mg/day for 4 weeks, mean steady-state imirestat concentration appeared to be dose proportional, although the time required to achieve steady state decreased with increasing dose. The mean effective half-life for accumulation ranged from 54 to 98 hr, suggesting that the very slow elimination of drug at low concentrations did not produce disproportionate accumulation of drug at these doses. Mean oral clearance was independent of dose, ranging from 30 to 45 ml/min. At the 2-, 5-, and 20-mg doses, one subject in each group had steady-state concentrations two- to fourfold greater than any of the other five subjects at the same dose, although the reason for this was not apparent from these data. The overall kinetic profile of these data was suggestive of dose-dependent pharmacokinetics resulting from nonlinear tissue binding of imirestat.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1901648 TI - The effects of hemodilution, pH, and protamine on lidocaine plasma protein binding and red blood-cell uptake in vitro. PMID- 1901649 TI - Enhanced bioavailability of subcutaneously injected insulin by pretreatment with ointment containing protease inhibitors. AB - The present study was undertaken to develop an ointment preparation containing a protease inhibitor for stabilizing subcutaneously injected insulin. The ointment containing the protease inhibitor, gabexate mesilate or nafamostat mesilate, was applied to the skin around the insulin injection site. Three results were obtained. First, gabexate and nafamostat inhibited insulin degradation in subcutaneous tissue homogenates in vitro. Second, after application of gabexate or nafamostat ointment, an appreciable amount of gabexate or nafamostat appeared in the subcutaneous tissue of rats or hairless mice and their concentrations were comparable to those seen in the in vitro experiment. Third, insulin degradation at the subcutaneous injection site in the rat was depressed after pretreatment with gabexate or nafamostat ointment. Pretreatment with gabexate or nafamostat ointment increased the plasma immunoreactive insulin (IRI) levels and the hypoglycermic effect of insulin in healthy volunteers. These results indicate that gabexate or nafamostat ointments stabilize subcutaneously injected insulin. PMID- 1901651 TI - Methylation and demethylation reactions of guanine nucleotide-binding proteins of retinal rod outer segments. AB - Retinal transducin was previously shown to be farnesylated on its gamma subunit. This farnesylation reaction on a cysteine residue near the carboxyl terminus is followed by peptidase cleavage at the cysteine. Thus the modified cysteine becomes the carboxyl terminus. It is shown here that the free carboxyl group can be methylated by an S-adenosyl-L-methionine-dependent methyltransferase associated with the rod outer segment membranes. This process can be inhibited by S-adenosyl-L-homocysteine and sinefungin. Moreover, synthetic N-acetyl-S-farnesyl L-cysteine, but not N-acetyl-L-cysteine, is a substrate for the enzyme. Rapid demethylation of N-acetyl-S-farnesyl-L-cysteine methyl ester can be observed in the membranes. Transducin is also enzymatically demethylated by the rod outer segment membranes. Moreover, the 23- to 29-kDa small G proteins are methylated and demethylated in this system. These data suggest that methylation/demethylation may play a regulatory role in visual signal transduction. PMID- 1901650 TI - Structure of the human gene and two rat cDNAs encoding the alpha chain of GTP binding regulatory protein Go: two different mRNAs are generated by alternative splicing. AB - Go is a specific class ("other") of signal-transducing heterotrimeric GTP-binding proteins (G proteins) that is expressed in high levels in mammalian brain. We have cloned two different rat cDNAs encoding the alpha subunit of Go (Go alpha-1 and Go alpha-2) and a human Go alpha chromosomal gene. The human Go alpha gene spans more than 100 kilobases and contains 11 exons, including one noncoding exon in the 3' flanking region. The 5' flanking region is highly G + C-rich and contains five G.C boxes (Sp1 binding sites) but no TATA box. Exons 7 and 8 coding for amino acid residues 242-354 of Go alpha protein are duplicated (referred to as exons 7A, 7B, 8A, and 8B). It was found that exons 7A and 8A code for Go alpha 1, and 7B and 8B code for Go alpha-2. This indicates that two different Go alpha mRNAs may be generated by alternative splicing of a single Go alpha gene. The splice sites of the Go alpha-1 and Go alpha-2 genes are completely identical with those encoding human inhibitory G protein alpha subunits Gi2 alpha and Gi3 alpha [Itoh, H., Toyama, R., Kozasa, T., Tsukamoto, T., Matsuoka, M. & Kaziro, Y. (1988) J. Biol. Chem. 263, 6656-6664] and also transducin G protein alpha subunit Gt1 alpha [Raport, C. J., Dere, B. & Hurley, J. (1989) J. Biol. Chem. 264, 7122 7128]. Sequence homology and conservation of the exon-intron organization indicate that the genes coding for Go alpha, Gi2 alpha, Gi3 alpha, Gt1 alpha, and probably Gi1 alpha may be evolved from a common progenitor. Like Go alpha-1, Go alpha-2 is expressed mainly in brain. PMID- 1901652 TI - Regulation of transforming growth factor beta 1 gene expression by the product of the retinoblastoma-susceptibility gene. AB - Transforming growth factor beta (TGF-beta) isoforms inhibit the growth of many cell types and block progression of the cell cycle by inhibiting events in late G1 phase. The retinoblastoma gene product, RB, also has properties of a cell cycle regulatory factor. It remains underphosphorylated in the presence of TGF beta and has been shown to repress the activity of the c-fos promoter, resulting in inhibition of transit through the cell cycle. These observations led us to examine effects of human RB on the expression of the human TGF-beta 1 gene. Using chimeric TGF-beta 1 promoter-chloramphenicol acetyltransferase gene constructs, we show that RB induces TGF-beta 1 gene expression in CCL-64 mink lung epithelial cells and A-549 human lung adenocarcinoma cells but represses its expression in NIH 3T3 and AKR-2B mouse cells. Several sequences homologous to the c-fos RB control element were identified in the TGF-beta 1 promoter. These results demonstrate that human RB can regulate TGF-beta 1 gene expression negatively or positively depending on the cell type. PMID- 1901653 TI - An idiotypic network model of AIDS immunopathogenesis. AB - Considerations from a network theory of the immune system suggest that human immunodeficiency virus and allogeneic stimuli may act synergistically to cause AIDS. The immune responses to these stimuli include two components that are directed against each other. In some AIDS risk groups other antigens that mimic major histocompatibility complex antigens may substitute for allogeneic stimuli. Implications for the prevention of AIDS are discussed. PMID- 1901654 TI - Site-specific integration of mycobacteriophage L5: integration-proficient vectors for Mycobacterium smegmatis, Mycobacterium tuberculosis, and bacille Calmette Guerin. AB - Mycobacteriophage L5, a temperate phage of mycobacteria, integrates site specifically into the Mycobacterium smegmatis chromosome. We have identified the int gene and attP site of L5, characterized the chromosomal attachment site (attB), and constructed plasmid vectors that efficiently transform M. smegmatis through stable site-specific integration of the plasmid into the bacterial genome. These integration-proficient plasmids also efficiently transform slow growing mycobacteria such as the pathogen Mycobacterium tuberculosis and the vaccine strain bacille Calmette-Guerin (BCG). The ability to easily generate stable recombinants in these slow-growing mycobacteria without the requirement for continual selection is of particular importance for the construction of recombinant BCG vaccines and for the isolation and characterization of mycobacterial pathogenic determinants in animal model systems. Integration vectors of this type should be of general use in a number of additional bacterial systems where temperate phages have been identified. PMID- 1901655 TI - The arflike gene encodes an essential GTP-binding protein in Drosophila. AB - We have identified a Drosophila gene (arflike, arl) encoding a protein that is structurally related (approximately 55% identity) to the ADP-ribosylation factors (ARFs) of yeast and mammals. Biochemical analyses of purified recombinant arl encoded protein revealed properties similar to the ARF proteins, including the ability to bind and hydrolyze GTP. Clear functional differences between arl and ARF proteins, including a complete lack of ARF activity, suggest that arl is not a functional homolog of ARF. A recessive lethal arl mutation was recovered, demonstrating that the arl locus is an essential gene. We conclude that the arl locus encodes an essential member of the ARF subfamily of small GTP-binding proteins in Drosophila. PMID- 1901656 TI - Thyrotropin-releasing hormone regulation of human TSHB expression: role of a pituitary-specific transcription factor (Pit-1/GHF-1) and potential interaction with a thyroid hormone-inhibitory element. AB - Regulation of human thyrotropin beta subunit gene (TSHB) expression by thyrotropin-releasing hormone (TRH) was examined in a clonal rat pituitary-cell line (GH3). Transient expression studies were done with various 5'-flanking DNA sequences of TSHB coupled to reporter gene chloramphenicol acetyltransferase. Deletion analysis defined two discrete regions (-128 to -92 base pairs and -28 to +8 base pairs) that each mediated an approximately 2-fold TRH induction. The upstream site contains a DNA sequence with close homology to the DNA-binding site for a pituitary-specific transcriptional factor Pit-1/GHF-1. DNase I footprinting analysis of mouse thyrotropic tumor extract as well as DNA-transfection studies using an expression vector containing an N-terminal deletion of Pit-1/GHF-1 cDNA suggest that Pit-1/GHF-1 or a closely related protein in the thyrotroph mediates TRH responsiveness of this gene. In addition, the downstream site overlaps with the recently characterized thyroid hormone-inhibitory element of TSHB. In fact, deletion of DNA sequences important in thyroid hormone-receptor binding (c erbAB/c-ERBA2) from +3 to +8 base pairs, significantly reduced (30%) TRH responsiveness. The location of a TRH-stimulatory element near a thyroid hormone inhibitory element may allow for fine control of TSHB expression in vivo. PMID- 1901658 TI - Exonucleolytic proofreading of leading and lagging strand DNA replication errors. AB - We have asked whether exonucleolytic proofreading occurs during simian virus 40 origin-dependent, bidirectional DNA replication in extracts of human HeLa cells. In addition, we have compared the fidelity of leading and lagging strand DNA synthesis. In a fidelity assay that scores single-base substitution errors that revert a TGA codon in the lacZ alpha gene in an M13mp vector, providing an excess of a single dNTP substrate over the other three dNTP substrates in a replication reaction generates defined, strand-specific errors. Fidelity measurements with two vectors having the origin of replication on opposite sides of the opal codon demonstrate that error rates for two different A.dCTP and T.dGTP mispairs increase when deoxyguanosine monophosphate is added to replication reaction mixtures or when the concentration of deoxynucleoside triphosphates is increased. The data suggest that exonucleolytic proofreading occurs on both strands during bidirectional replication. Measurements using the two simian virus 40 origin containing vectors suggest that base substitution error rates are similar for replication of the leading and lagging strands. PMID- 1901657 TI - Product of the Pseudomonas aeruginosa gene pilD is a prepilin leader peptidase. AB - The related type IV pilins produced by Pseudomonas aeruginosa, Neisseria gonorrhoeae, Bacteroides nodosus, and Moraxella bovis are synthesized as precursors with short, six- or seven-amino acid N-terminal leader peptides. We have previously observed that P. aeruginosa mutations in pilD, a gene required for pilus biogenesis, result in the accumulation of unprocessed prepilin in the membrane and a general defect in the excretion of a number of extracellular enzymes. An endopeptidase activity has been detected in detergent-solubilized inner membrane of P. aeruginosa and shown to correctly cleave the prepilin of P. aeruginosa and N. gonorrhoeae. It is absent from pilD mutants, increased by pilD overexpression, and conferred on Escherichia coli by the introduction of the pilD gene. The pilD gene product, purified by immunoaffinity chromatography with antibody to a PilD-derived synthetic peptide, was identified with the endopeptidase. PilD appears to be a prototype of a class of enzymes that process not only type IV pilin precursors but also components of a protein-excretion apparatus of Gram-negative bacteria. PMID- 1901659 TI - Generation of sensory neurons is stimulated by leukemia inhibitory factor. AB - The processes that regulate the development of peripheral neurons from their precursors in the embryonic neural crest are essentially unknown. In this report, we show that leukemia inhibitory factor stimulates the generation of neurons in cultures of mouse neural crest. These neurons have the morphology of sensory neurons and contain neuropeptides found in mammalian sensory neurons. Consistent with these neurons being of the sensory lineage is the finding that they arise from nondividing precursors within the neural crest. In addition, we show that leukemia inhibitory factor supports the generation and/or maturation of sensory neurons in cultures of cells obtained from embryonic dorsal root ganglia. In cultures of postnatal dorsal root ganglia, which contain mature sensory neurons, leukemia inhibitory factor acts directly as a survival molecule on the majority of neurons. PMID- 1901660 TI - Tropical eosinophilia: clinical and physiological response to diethylcarbamazine. AB - Fifty patients with tropical eosinophilia were studied clinically and physiologically, before and after a standard 3-week course of diethylcarbamazine. Before treatment the main physiological abnormality was a reduction in the carbon monoxide transfer factor. One month after the start of treatment most patients had shown a marked symptomatic improvement, but peripheral blood eosinophilia persisted in 52%, radiographic abnormalities in 44%, cough in 22% and chest signs in 8%. Significant improvement was noted in almost all aspects of lung function including blood gases, but the mean values for forced expiratory volume in one second, forced vital capacity, transfer factor and transfer coefficient continued to be significantly lower than predicted values. This study demonstrates the incomplete reversal of clinical, haematological, radiological and physiological changes in tropical eosinophilia one month after starting a 3-week course of diethylcarbamazine. PMID- 1901661 TI - Principal component analysis of various respiratory function tests: the relationship between factor score and severity of pulmonary circulatory disorder in chronic obstructive pulmonary disease. AB - The relationship between pulmonary haemodynamics and values of various respiratory function tests was studied in patients with mild chronic obstructive pulmonary disease (COPD) and the following results were obtained. (1) The value of mean pulmonary artery pressure (mPAP) at rest in COPD patients was slightly elevated to 19.4 mmHg on average compared with our control value of less than 18 mmHg. (2) Analysis of the data of 11 routine respiratory function tests in 88 COPD patients extracted two principal components: an index of the expiratory function and an index for overinflation of the lung. (3) In individual patients, mPAP expressed the severity of pulmonary circulatory disorder roughly inverse to the factor score of the first principal component (index of expiratory function) but not to that of the second principal component (overinflation of the lung). (4) Discriminant analysis was performed in all 88 COPD patients according to data from the 11 respiratory function tests. The probability of mPAP being above or below 18 mmHg was 18.2%. (5) The relationship between the predicted EPOI value and the factor score was similar to that between mPAP and the factor score. EPOI (exercise pulmonary artery pressure-oxygen consumption index) was calculated with the following equation: EPOI = (mPAPex#-mPAPrest)/[VO2ex-VO2rest)/BSA##). On the other hand, EPOIpred was calculated with the prediction equation obtained from multiple linear regression (dependent variable; EPOI, independent variable; respiratory function). PMID- 1901663 TI - [Central lesions in neurofibromatosis: clinical, MRI and histopathologic correlations. An attempted classification]. AB - The National Institute of Health Consensus Panel on Neurofibromatosis (NF) recently recognized 2 distinct forms of NF (NF-1 and NF-2) and stated that variant forms may exist. We selected 30 patients who fulfilled the criteria of NF 1 or whose condition was consistent with NF-2. All patients showed pathological magnetic resonance images (MRI), and in 19 cases confirmation was obtained from histopathology. We established correlations between the site and nature of the lesions on the one hand and the diagnostic criteria of NF on the other hand, there by hoping to contribute to a better knowledge and classification of neurofibromatosis. Nineteen patients had only intraparenchymatous lesions of the central nervous system (CNS) and fulfilled the criteria of NF-1; histopathological examination demonstrated pilocytic astrocytoma in 8 cases. Eleven patients showed only extra-axial lesions; 8 of them had criteria suggestive of NF-2, except for familial history. Pathological examination revealed either acoustic, pluriradicular, peripheral or mixed schwannomas (7/8) or pluriradicular ganglioneuromas (1/8). Two patients had unilateral extra-axial pluriradicular cervical lesions and fulfilled the diagnostic criteria of NF-1; pathological examination revealed neurofibroma in both cases. One female patient had both intra- and extra-axial lesions that fulfilled the criteria of NF-1 and NF-2, suggesting the existence of a mixed form (NF-3). PMID- 1901664 TI - [Central neurologic forms of Waldenstrom's disease. Bing-Neel syndrome. 3 cases]. AB - Three cases of central nervous system involvement in Waldenstrom's macroglobulinemia (Bing Neel's syndrome) are reported. Such cases are unusual and have a poor prognosis. One patient received chemotherapy including BCNU, cyclophosphamide, vincristine, melphalan and prednisolone, which was followed by a dramatic improvement. The pathogenesis of Bing Neel's syndrome is discussed. PMID- 1901662 TI - Regulation of glycogen resynthesis following exercise. Dietary considerations. AB - With the cessation of exercise, glycogen repletion begins to take place rapidly in skeletal muscle and can result in glycogen levels higher than those present before exercise. Understanding the rate-limiting steps that regulate glycogen synthesis will provide us with strategies to increase the resynthesis of glycogen during recovery from exercise, and thus improve performance. Given the importance of muscle glycogen to endurance performance, various factors which may optimise glycogen resynthesis rate and insure complete restoration have been of interest to both the scientist and athlete. The time required for complete muscle glycogen resynthesis after prolonged moderate intensity exercise is generally considered to be 24 hours provided approximately 500 to 700g of carbohydrate is ingested. Muscle glycogen synthesis rate is highest during the first 2 hours after exercise. Ingestion of 0.70g glucose/kg bodyweight every 2 hours appears to maximise glycogen resynthesis rate at approximately 5 to 6 mumol/g wet weight/h during the first 4 to 6 hours after exhaustive exercise. Further enhancement of glycogen resynthesis rate with ingestion of greater than 0.70g glucose/kg bodyweight appears to be limited by the constraints imposed by gastric emptying. Ingestion of glucose or sucrose results in similar muscle glycogen resynthesis rates while glycogen synthesis in liver is better served with the ingestion of fructose. Also, increases in muscle glycogen content during the first 4 to 6 hours after exercise are greater with ingestion of simple as compared with complex carbohydrate. Glycogen synthase activity is a key component in the regulation of glycogen resynthesis. Glycogen synthase enzyme exists in 2 states: the less active, more phosphorylated (D) form which is under allosteric control of glucose-6-phosphate, and the more active, less phosphorylated (I) form which is independent of glucose-6-phosphate. There is generally an inverse relationship between glycogen content in muscle and the percentage synthase in the activated (I) form. Exercise and insulin by themselves activate glycogen synthase by conversion to glycogen synthase I. Although small changes in the activity ratio (% I form) can lead to large changes in the rate of glycogen synthesis, glycogen synthase I appears to increase very little (approximately 25%) in response to glycogen depletion and returns to pre-exercise levels as glycogen levels return to normal. Thus glycogen resynthesis, which may increase 3- to 5-fold, may also be influenced by glucose-6-phosphate, which can activate glycogen synthase in the D form.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1901665 TI - Endemic infectious diseases of the Middle East. PMID- 1901666 TI - Traditional perceptions of marasmus in Pakistan. AB - One hundred and fifty mothers of under-5 children clinically identified as malnourished were interviewed in their homes in katchi abadis (squatter settlements) of Karachi. A variety of ethnic and religious groups were represented. Mothers were shown a photograph of a child with third-degree malnutrition (marasmus) and were asked what might be wrong with the child. Virtually of the mothers said that they had seen the condition, typically identifying it as sukhay ki bimari (Urdu: 'the disease of dryness and thinness'). The majority said that diarrhea predisposed to sukhay ki bimari, and vice versa, but only 3 of the 150 mothers said that diarrhea and/or lack of food could, in themselves, cause the condition. Instead, most said that the usual cause was contact with a woman who had a marasmic child or was otherwise in a state of ritual impurity. The mediating factor was said to be a saya ('shadow, influence') emanating from such a person and ultimately linked with the spirit world. Although the condition was judged to have a very poor prognosis, mothers described various magico-religious therapies that could be tried. Treatment by physicians or by giving more food was considered ineffective or even detrimental, and hiding of such children was reportedly common because of social stigma. Subsequent inquiries carried out by the author in Chitral in northwestern Pakistan produced similar findings except that there, the condition was known as moordasip and was more overtly associated with fright and spirit possession. In Karachi, 45 of the 150 mothers interviewed had children with third-degree malnutrition according to weight-for-age criteria, 15 of whom died in the course of the study. In these 45 families especially, early bottlefeeding had occurred, sometimes reportedly because of fear that the mother was a carrier of a saya and could pass it on through her milk. Most mothers had only sketchy knowledge of suitable weaning foods and an appropriate timetable for introducing such foods, and many showed little awareness of what their children were eating once they reached the toddler stage. Implications for the identification and treatment of marasmic children are discussed. A brief summary of crosscultural beliefs surrounding marasmus and the 'hard to raise' child is included. PMID- 1901667 TI - Seizures in patients simultaneously receiving theophylline and imipenem or ciprofloxacin or metronidazole. AB - Five patients had apparently drug-induced seizures while simultaneously receiving theophylline and either imipenem (three patients), ciprofloxacin (one patient), or ciprofloxacin and metronidazole (one patient). Seizures ceased upon reduction in dosage or discontinuation of the suspected offending agents. Imaging studies failed to reveal new structural lesions in the central nervous system in any patient, and only one had a history of neurologic disease. Although the exact mechanism for seizure induction cannot be determined from these cases, potential drug interactions exist, because theophylline, imipenem, and ciprofloxacin are all believed to increase excitation of the central nervous system by inhibition of gamma-aminobutyric acid binding to receptors. In addition, ciprofloxacin decreases the clearance of theophylline from the body, predisposing the patient to elevated theophylline levels. Physicians prescribing theophylline with imipenem, ciprofloxacin, or metronidazole should carefully monitor patients for indications for drug therapy, drug dosage, organ impairment affecting drug metabolism, and signs of toxicity. Seizures may accompany oral theophylline therapy, even at "therapeutic" serum theophylline concentrations. PMID- 1901668 TI - Purpura fulminans and adrenal hemorrhage due to group Y meningococcemia in an elderly woman. AB - A 70-year-old previously healthy woman was admitted with a 1-day history of malaise, sore throat, nausea, vomiting, rigors, and confusion. She was found to be in septic shock with purpura fulminans and disseminated intravascular coagulation. She died within 36 hours of admission. Blood cultures grew Neisseria meningitidis group Y. Necropsy revealed evidence of shock and bilateral adrenal hemorrhage. PMID- 1901669 TI - [Evaluation of irradiation techniques in breast carcinoma using dose-volume histograms. Comparison of the heart and lung exposure]. AB - For irradiation of the internal mammary lymph nodes (IMN), together with irradiation of the breast the commonly used treatment techniques are of three types: 1. two tangential opposed fields, 2. three field plans with a separate "straight on" IMN-field, or 3. with a separate "angled" IMN-field. To determine lung and heart volumes and doses for these techniques, dose-volume-histograms in 30 patients were analyzed. The optimum dose distribution was achieved with the "angled" field technique and an appropriate combination of electrons and 60Co gamma radiation for the IMN-field. (The beam mixture used was 40% 60Co beam and 60% electron beam.) The least possible dose to the lung was obtained with the "straight-on" field technique and the least possible dose to the heart with the separate "angled" IMN-field technique. PMID- 1901670 TI - [Incidence of osteoradionecrosis after combined radiotherapy-chemotherapy of head and neck tumors]. AB - Combined modality therapy, consisting of radiation, chemotherapy and surgery are used to treat primary tumours aiming to preserve function and increase tumour control. In the present prospective trial 112 patients underwent combined preoperative radio-chemotherapy, 35 patients were treated with combined radio chemotherapy as only treatment. At a median follow-up of 26 months eight patients (2.8%) have developed an osteo-radionecrosis, which is comparable with data from the literature. When known risk factors are avoided the incidence of osteo radionecrosis is not increased following combined therapy. The most important factors for development of osteo-radionecrosis following radio-chemotherapy are large tumours and tumour infiltration in the mandible. PMID- 1901671 TI - Preliminary results of clinical application of reactor fast neutrons in radiation and combined therapy of patients with laryngeal carcinoma. AB - Since 1985 treatment of cancer patients on BR-10 reactor has been carried out in the Institute of Medical Radiology. Till May, 1989, 78 patients have received mixed gamma-neutron therapy and combined treatment (preoperative radiation therapy and surgery). Marked late local reactions (perichondritis) were observed only in three (7%) out of 42 patients treated with radical radiation therapy alone. 43 patients had a follow-up period of two years. Among them T2 tumors were registered in six (14%) cases, T3 in 28 (65%) cases, T4 in nine (21%) cases. Regional metastases were observed in 13 (30%) patients. 19 out of 27 patients (70%) treated with radical gamma-neutron therapy and 13 out of 16 patients (81%) treated with combined therapy using reactor fast neutrons as preoperative radiation therapy are alive two years without evidence of the disease. PMID- 1901673 TI - [Gastrointestinal flora and health in man and animal]. AB - A balanced and stable gastro-intestinal microflora is of vital importance for the optimum function of the gastro-intestinal tract and consequently for the health of man and animals. The gastro-intestinal microflora is a very complex ecosystem, the current knowledge of which is still very limited. It is obvious that the intestinal flora has a protective function (prevention of infection). In addition it has a positive effect on nutrition (digestion, effects on physiology, production of vitamins). Changes in diet, stress, the use of antibiotics and excessive hygiene all bring about changes in the micro-biological ecosystem and consequently changes in health conditions. Knowledge about the microbial ecology of the intestine is also of importance in the prevention of zoonoses. Recently, increasing attention is being paid to the development of methods to influence the composition of the gastro-intestinal microflora in man and animals by probiotics (dried cells or fermented food). These concepts will be dealt with in the present paper and, in addition some of the possible uses will be discussed. PMID- 1901672 TI - Tuberculous pleural effusions: increased culture yield with bedside inoculation of pleural fluid and poor diagnostic value of adenosine deaminase. AB - A prospective study of 111 adult patients with a pleural effusion was carried out in an area with a high prevalence of tuberculosis to compare the yield of bedside with laboratory inoculation of pleural fluid, and the yield and speed of a radiometric mycobacterial culture system (BACTEC) with that of conventional culture. The use of adenosine deaminase activity in pleural fluid as a diagnostic test for tuberculosis was also evaluated. In the 62 cases of tuberculosis confirmed histologically or by culture, or both, the BACTEC system had the same culture yield as conventional mycobacterial culture (positive in 14 cases-23%), but was significantly faster (18 versus 33 days). Bedside inoculation had a culture yield significantly higher than laboratory inoculation in the 24 patients tested (11 versus four). The remaining three diagnostic categories were malignant (28), miscellaneous (10), and undiagnosed (11). Median adenosine deaminase activity was significantly higher in tuberculous effusions than in any of the other categories, but there was considerable overlap between the groups. It is concluded that the BACTEC system is significantly faster than conventional mycobacterial culture and that bedside inoculation of pleural fluid substantially increases culture yield. Adenosine deaminase does not provide as valuable a diagnostic test of pleural tuberculosis as has been suggested. PMID- 1901674 TI - Absence of effects of thymopentin on murine host resistance to Listeria monocytogenes. AB - The effects of various doses of Thymopentin, the synthetic 5 aminoacid fragment of thymopoietin injected on d -4 and d -1 on murine host resistance to Listeria monocytogenes were tested. The experiments did not reveal any regular dose-effect relationship; i.e. no or only marginal (more often small negative rather than positive) effects were observed on clearance and on resistance neither during the T cell independent first hour or the first 2 days of infection in euthymic or thymus deficient nude mice, nor during the T cell dependent phase after 2 days of infection in euthymic mice. Also survival of mice was not increased in a regular dose-effect relationship with dose ranges of Thymopentin from 0.3 ng-30 mg per 30 g mouse; furthermore, injections of 3 micrograms per 30 g mouse for varying time intervals from -3 days before up to 6 days after infection had no protective effect. Thus Thymopentin apparently does not induce measurable macrophage activation directly or cannot increase macrophage activation mediated by T cells in euthymic mice nor does it induce adequate T cell responses in nude mice to promote improved resistance to Listeria. PMID- 1901675 TI - Deletion of self-reactive T cells in the donor-derived T cells but not in the host-derived T cells in fully allogeneic radiation chimeras. Mls-reactive T cells in allogeneic radiation chimeras. AB - Kinetics of T cells bearing V beta 6 capable of recognizing Mls-1a were examined in the thymus and peripheral lymphoid organs of two allogeneic bone marrow chimeras; AKR/J(H-2k, Thy1.1,Mls-1a)----C3H/He(H-2k, Thy1.2,Mls-1b) and AKR/J--- C57BL/6(H-2b,Thy1.2, Mls-1b). Sequential appearance of host- and donor-derived T cells occurred in the thymus and the peripheral lymphoid organs of both AKR--- C3H and AKR----B6 chimeras. The first cells to repopulate the thymus were Thy1.2+ host-derived radioresistant cells, which were synchronized in their development. The host-derived cells in thymus of AKR----B6 chimeras differentiate more rapidly than those in AKR----C3H chimeras. An almost complete replacement from host derived cells to donor-derived cells occurred by day 21 after reconstitution in AKR----C3H and AKR----B6 chimeras. In the donor-derived thymocytes, none of CD4- or CD8-single positive thymocytes expressed high density of V beta 6 in either AKR----C3H or AKR----B6 chimeras, whereas the host-derived thymocytes in AKR--- B6 chimeras contained an appreciable number of CD4-single positive thymocytes bearing V beta 6. In the peripheral lymphoid organs, T cells bearing V beta 6 were virtually abolished in Thy1.1+ cell pool of both AKR----C3H and AKR----B6 chimeras. While V beta 6+ T cells of host-origin were detected in the peripheral lymphoid organs in AKR----B6 chimeras. These result indicated that the donor derived mature T cells showed deletion of V beta 6 in the thymus and the peripheral lymphoid organs in both AKR----C3H and AKR----B6 chimeras, whereas lack of V beta 6 deletion was observed in the host-derived mature T cells in the AKR----B6 chimeras. These results suggested that the host-derived thymocytes may likely to escape undergoing a negative selection against donor-phenotype in the radiation bone marrow chimeras. PMID- 1901676 TI - Serologic and DNA follow-up data from HBsAg-positive patients treated with orthotopic liver transplantation. AB - Fifteen hepatitis B surface antigen (HBsAg) positive patients treated with orthotopic liver transplantation were studied to determine whether any clinical, serologic, or histologic data were predictive for recurrent hepatitis B infection leading to graft failure. Six patients died early, one due to primary graft nonfunction and the remaining five due to septic complications. There were nine patients surviving longer than two months, eight of whom are alive at a mean follow-up of 556 days. HBsAg and hepatitis B core antibody (anti-HBc) reappeared in the sera of all survivors after a variable transient period of clearance. One patient died 3 months posttransplant of fungal sepsis and was found to have histologic evidence for recurrent hepatitis and positive immunoperoxidase staining postmortem. The remaining eight survivors are home and clinically well, with no histologic evidence of hepatitis. Seven of these eight patients have hepatitis B viral DNA in their sera. We conclude that while there is a high early mortality, usually from sepsis, none of the serologic, histologic, or DNA data analyzed can be used to predict graft loss from recurrent hepatitis. No grafts have been lost due to recurrent hepatitis B in this series, and therefore we believe that HBsAg positive patients should not be excluded from transplantation. PMID- 1901677 TI - Induction of unresponsiveness to organ allografts. A comparison of different immunosuppressive protocols in DA and WF strains of rats. PMID- 1901678 TI - Hypertrophy of clitoral hood: presenting sign of neurofibromatosis in female child. AB - Although clitoral involvement with neurofibromatosis is rare, all cases previously reported have described clitoral hypertrophy due to neurofibromas of the clitoral corpora. We report on a patient who had localized enlargement of the prepuce only, with no evidence of neurofibromatous infiltration. In all cases, diagnosis of clitoromegaly requires basic chromosomal and endocrinologic evaluation. However, recognition of its association with neurofibromatosis due to either neurofibromas of the genitalia or localized genital hypertrophy may spare the patient an unnecessary or invasive evaluation. Because of an association with urinary tract neurofibromas, the patient with genital involvement should have cystoscopy. Clitoroplasty with sparing of the neurovascular bundle and glans is the preferred method of management of the enlarged clitoris. PMID- 1901679 TI - Two new uses of 8-F feeding tube in performing injecting urethrograms. AB - A modification of a previously described method for visualizing the urethrovesical junction is described. This modification is easier to perform, less messy, and obtains superior images to the method now used. A new method for outlining urethral strictures is also described. Both methods use an 8-F feeding tube. PMID- 1901680 TI - Cost benefit of pharmacologic erection program. PMID- 1901681 TI - Perturbation of host-cell membrane is a primary mechanism of HIV cytopathology. AB - Cytopathic viruses injure cells by a number of different mechanisms. The mechanism by which HIV-1 injures T cells was studied by temporally examining host cell macromolecular syntheses, stages of the cell cycle, and membrane permeability following acute infection. T cells cytopathically infected at an m.o.i. of 1-5 grew normally for 24-72 hr, depending on the cell line, followed by the first manifestation of cell injury, slowing of cell division. At that time significant amounts of unintegrated HIV DNA and p24 core protein became detectable, and acridine orange flow cytometric cell cycle studies demonstrated the presence of fewer cells in the G2/M stage of the cell cycle. There was no change in the frequency of cells in the S-stage, and metabolic pulsing with radioactive precursors demonstrated that host-cell DNA, RNA, and protein syntheses were normal at that time and normal up to the time cells started to die (approximately 24 hr later), when all three decreased. Cellular lipid synthesis, however, was perturbed when cell multiplication slowed, with phospholipid synthesis reduced and neutral lipid synthesis enhanced. Permeability of the host cell membrane to small molecules, such as Ca2+ and sucrose, was slightly enhanced early postinfection, and by the time of slowing of cell division, host membrane permeability was greatly increased to both Ca2+ and sucrose (Stokes radius 5.2 A) but not to inulin (Stokes radium 20 A). These changes in host-cell membrane permeability and phospholipid synthesis were not observed in acutely infected H9 cells, which are not susceptible to HIV cytopathology. Thus, HIV-1 appeared to predominantly injure T cells by perturbing host-cell membrane permeability and lipid synthesis, which is similar to the cytopathic mechanisms of paramyxoviruses. PMID- 1901682 TI - Sequence analysis of infectious pancreatic necrosis virus genome segment B and its encoded VP1 protein: a putative RNA-dependent RNA polymerase lacking the Gly Asp-Asp motif. AB - The genome segment B sequence of infectious pancreatic necrosis virus was determined for both the Jasper and Sp serotypes. The sequences are 2784 and 2630 bp long, respectively, and contain a single large open reading frame encoding the VP1 protein, the putative RNA-dependent RNA polymerase (RdRp) of IPNV. The proteins exhibit an 88% homology with each other, but only 41% with infectious bursal disease virus (IBDV) VP1, another member of the Birnaviridae. Despite the low overall homology between the IPNV and IBDV VP1 proteins, homologous regions were detected within the central portion of the proteins. The carboxy-proximal regions of the VP1, which contain very low amino acid homology, displayed evidence of conservation in structural features such as a hydrophilic, highly basic domain. Consensus sequences associated with GTP-binding proteins and RdRps were also detected in VP1. However, unlike the RdRps associated with single stranded plus RNA viruses, the birnavirus RdRp lacks the Gly-Asp-Asp motif characteristic of this enzyme family. PMID- 1901683 TI - Total hip and knee replacements. PMID- 1901684 TI - Is DRG useful in orthopedics? AB - The increasing hospital costs have provoked discussions about Diagnose Related Groups (DRG) and its role in controlling the growth of hospital budgets. The relevance to current operation statistics and the structure of DRG in orthopedics are analyzed. The direct application of DRG to Scandinavian statistics does not appear to be reliable. PMID- 1901685 TI - Occurrences of antibodies against Streptococcus pneumoniae, Haemophilus influenzae and Branhamella catarrhalis in middle ear effusion and serum during the course of acute otitis media. AB - The occurrence of IgG, IgM and IgA class antibodies against a type-specific capsular polysaccharide of Streptococcus pneumoniae (Pn) and against a whole cell antigen of Haemophilus influenzae (Hi) and Branhamella catarrhalis (Br) was studied using the ELISA method on middle ear effusion (MEE) samples of 85 patients and paired serum samples of 40 patients during the course of acute otitis media (AOM). Although specific antibodies to all of these three bacteria appeared in MEE during the course of an AOM episode, antibodies against the infecting bacteria of that particular AOM episode were more often prominent. The antibodies were also detectable in the MEE without simultaneous presence in the serum. The middle ear infection was prolonged more often if specific antibodies to the infecting bacterium could not be detected in the MEE obtained at the beginning of the AOM attack. The present study indicates that AOM caused by Pn, Hi or Br may induce both a systemic and a local production of specific antibodies against the causative organisms during the course of otitis media. The occurrence of such antibodies in MEE seems to play a major role in the resolution of AOM. PMID- 1901687 TI - Ultrastructural study of cytochemical localization of carbonic anhydrase in the inner ear. AB - Vibratome sections were stained for cytochemical localization of carbonic anhydrase (CA) activity in vestibular neuro-epithelium, spiral ligament and spiral limbus. The new finding is the localization of reaction products in the interdental cells of the spiral limbus, Claudius' cells, mesothelial cells of the lower border of spiral ligament, vestibular sensory cells and perilymphatic cells, which have not earlier been proved to have CA activity. The interdental cells showed the products only on the basolateral infoldings. Claudius' cells showed prominent products in the microvilli. In the vestibular sensory cells, the products were present only in the stereocilia and cuticular areas. The perilymphatic fibrocytes under the vestibular sensory epithelium, like the fibrocytes of the spiral ligament, revealed diffuse products throughout the whole cell. In the vestibular supporting cells and transitional cells, the reaction products were localized diffusely in the cytosol, but not in the secretory granules. In the long cell projections of the transitional cells, type II fibrocytes at spiral prominence, mesothelial cells at the uppermost region of the spiral ligament and Borghesan's zone, the localization of the reaction products was the same as that of the basolateral infoldings of the vestibular dark cells and marginal cells of stria vascularis shown previously. PMID- 1901686 TI - Amoxycillin/clavulanate versus amoxycillin in recurrent otitis media and therapeutic failure in children. AB - A total of 102 children with recurrent otitis media or therapeutic failure after treatment with phenoxymethyl penicillin were entered into a double-blind study with parallel groups, comparing treatment with amoxycillin/clavulanate suspension (Spektramox) for 7 days with amoxycillin suspension (Imacillin) for 10 days. Bacterial and clinical investigations were performed. A total of 91 patients were evaluated for efficacy at the first follow-up visit (10-12 days after start of treatment). Amoxycillin/clavulanate and amoxycillin showed equally high, satisfactory treatment results, i.e. more than a 90% response. Similarly, there was no statistically significant difference between the treatment groups at the second follow-up visit (about 30 days after start of treatment). Bacteriological cultures from the nasopharynx showed equal distribution of Haemophilus influenzae, Branhamella catarrhalis and Streptococcus pneumoniae between the study groups. Elimination of the initially occurring pathogens was equal in the two study groups with the exception of B. catarrhalis which was eliminated to a significantly higher extent with amoxycillin/clavulanate. Both drugs were well tolerated. In patients with recurrent otitis media or therapeutic failure, treatment with amoxycillin/clavulanate for 7 days results in high, satisfactory clinical effects and is comparable to treatment with amoxycillin for 10 days. PMID- 1901689 TI - Sequencing of the variant thyroxine-binding globulin (TBG)-Quebec reveals two nucleotide substitutions. AB - Thyroxine-binding globulin (TBG) is a liver glycoprotein that transports thyroid hormone in serum. In 1987 a variant TBG was discovered in an infant born in Quebec, following an investigation prompted by the finding of low blood thyroxine (T4) level on screening for neonatal hypothyroidism. This variant, TBG-Quebec, has cathodal shift on isoelectric focusing, reduced affinity for thyroxine, and markedly reduced stability. The latter property of the variant molecule is probably responsible for the partial TBG deficiency. We now report the results of sequencing of the entire coding region and exon-intron junctions of TBG-Quebec, which revealed two nucleotide substitutions; one, located in exon 3, changes the normal codon 283 of TTG (leucine) to that of TTT (phenylalanine), and the other, in exon 4, results in the replacement of the normal histidine-331 (CAT) by tyrosine (TAT). Allele-specific amplification (ASA) confirmed the cosegregation of the two nucleotide substitutions with the TBG-Quebec phenotype in individual members of this family. The substitution in codon 283, but not that in codon 331, has been previously described and, when occurring alone, does not alter the properties of the gene product. Thus, it appears that the replacement of histidine-331 by tyrosine is responsible for the observed altered properties of TBG-Quebec. However, the question of whether substitution of both amino acids is necessary for expression of the variant phenotype has yet to be answered. PMID- 1901688 TI - Analysis of N-acetylgalactosamine-4-sulfatase protein and kinetics in mucopolysaccharidosis type VI patients. AB - A sensitive and specific, monoclonal antibody-based immunoquantification assay has facilitated determination of the N-acetylgalactosamine-4-sulfatase (4 sulfatase) protein content in cultured fibroblasts from normal controls and mucopolysaccharidosis type VI (MPS VI) patients. The assay enabled the quantification of 4-sulfatase protein by using a panel of seven monoclonal antibodies and has shown that fibroblasts from 16 MPS VI patients contained less than or equal to 5% of the level determined for normal controls. Fibroblasts from the most severely affected patients contained the lowest levels of 4-sulfatase protein, usually with few epitopes detected, while fibroblasts from mildly affected patients had higher levels of 4-sulfatase protein, with all seven epitopes detected. The pattern of epitope expression is proposed to reflect the conformational changes in the 4-sulfatase protein that arise from different mutations in the 4-sulfatase gene. Immunoquantification in combination with a specific and highly sensitive 4-sulfated trisaccharide-based assay of enzyme activity in these MPS VI patient fibroblasts enabled the determination of residual 4-sulfatase catalytic efficiency (kcat/Km). The capacity of fibroblasts to degrade substrate (catalytic capacity) was calculated as the product of 4 sulfatase catalytic efficiency and the content of 4-sulfatase in fibroblasts. One patient, 2357, with no clinical signs of MPS VI but with reduced 4-sulfatase activity and protein (both 5% of normal) and dermatansulfaturia, had 5% of normal catalytic capacity. The other 15 MPS VI patient fibroblasts had 0%-1.4% of the catalytic capacity of fibroblasts from normal controls and were representative of the spectrum of MPS VI clinical phenotypes, from severe to mild.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1901690 TI - Pulsed-field electrophoresis screening for immunoglobulin heavy-chain constant region (IGHC) multigene deletions and duplications. AB - Genome regions containing multiple copies of homologous genes, such as the immunoglobulin (Ig) heavy-chain constant-region (IGHC) locus, are often unstable and give rise to duplicated and deleted haplotypes. Analysis of such processes is fundamental to understanding the mechanisms of evolution of multigene families. In the IGHC region, a number of single and multiple gene deletions, derived from either unequal crossing-over or looping-out excision, have been described. To study these haplotypes at the population level, a simple and efficient method for preparing large numbers of DNA samples suitable for pulsed-field gel electrophoresis (PFGE) analysis was set up, and a sample of 110 blood donors was screened. Deletions were found to be frequent, as expected on the basis of previous serological surveys for homozygotes. Furthermore, a number of multigene duplications, never identified before, were detected. The total frequency of individuals bearing rearranged IGHC haplotypes was 10%. The genes involved in these deletions and duplications were assessed by densitometric analysis of standard Southern blots hybridized with several IGHC probes; two types of deletion and two types of duplication could thus be characterized. These data provide further evidence of the instability of the IGHC locus and demonstrate that unequal crossing-over is the most likely origin of rearranged IGHC haplotypes; they also suggest that such recombination events may be relatively frequent. Moreover, the simplicity and effectiveness of the large-scale PFGE screening approach will be of great help in the study of multigene families and of other loci involved in aberrant recombinations. PMID- 1901691 TI - Cough-type asthma: a review. AB - Cough-type asthma is a well-defined entity. The patients typically have a chronic, nonproductive cough that is exacerbated by exercise and upper respiratory tract infections. Bronchial provocation maneuvers are helpful in diagnosing cough-type asthma in older children and adults. Bronchodilators are the mainstay of therapy, although some patients may require cromolyn sodium or inhaled corticosteroids. The natural history of this process suggests that approximately a third to a half of these patients may progress to "classical" asthma with wheezing. PMID- 1901692 TI - Anaphylaxis and desensitization to the murine monoclonal antibody used for renal graft rejection. AB - The murine monoclonal antibody muromonab CD3 is currently used to reverse acute renal graft rejection. We report a case of systemic anaphylaxis during a muromonab CD3 infusion despite pretreatment with systemic antihistamines and corticosteroids. Rapid intravenous desensitization was performed the following day without untoward reactions and daily muromonab CD3 infusions were successful in reversing renal graft rejection. A second rapid desensitization to CD3 was performed 1 month later without any complications. Serum muromonab CD3-specific IgG and IgE antibodies were detected in serum samples obtained after the anaphylactic reaction. The anaphylactic reaction to muromonoab CD3 monoclonal antibody could have been due to allergen-specific antibodies noted in postreaction serum or a cross-reactive antibody to mouse antigens or both. More importantly, this case illustrates that rapid desensitization can be performed successfully without serious complications; therefore, systemic anaphylaxis can develop in susceptible atopic individuals receiving muromonab CD3 monoclonal antibody for renal graft rejection. PMID- 1901693 TI - Antimicrobial resistance among enterococci. PMID- 1901694 TI - Killing of intracellular Mycobacterium tuberculosis by receptor-mediated drug delivery. AB - p-Aminosalicylic acid (PAS) conjugated to maleylated bovine serum albumin (MBSA) was taken up efficiently through high-affinity MBSA-binding sites on macrophages. Binding of the radiolabeled conjugate to cultured mouse peritoneal macrophages at 4 degrees C was competed for by MBSA but not by PAS. At 37 degrees C, the radiolabeled conjugate was rapidly degraded by the macrophages, leading to release of acid-soluble degradation products in the medium. The drug conjugate was nearly 100 times as effective as free PAS in killing the intracellular mycobacteria in mouse peritoneal macrophages infected in culture with Mycobacterium tuberculosis. The killing of intracellular mycobacteria mediated by the drug conjugate was effectively prevented by simultaneous addition of excess MBSA (100 micrograms/ml) or chloroquine (3 microM) to the medium, whereas these agents did not affect the microbicidal action of free PAS. These results suggest that (i) uptake of the PAS-MBSA conjugate was mediated by cell surface receptors on macrophages which recognize MBSA and (ii) lysosomal hydrolysis of the internalized conjugate resulted in intracellular release of a pharmacologically active form of the drug, which led to selective killing of the M. tuberculosis harbored by mouse macrophages infected in culture. This receptor-mediated modality of delivering drugs to macrophages could contribute to greater therapeutic efficacy and minimization of toxic side effects in the management of tuberculosis and other intracellular mycobacterial infections. PMID- 1901695 TI - Transferable imipenem resistance in Pseudomonas aeruginosa. AB - We isolated an imipenem-resistant strain, GN17203, of Pseudomonas aeruginosa. The strain produced a beta-lactamase that hydrolyzed imipenem. The beta-lactamase was encoded by a 31-MDa plasmid, pMS350, which belongs to incompatibility group P-9. The plasmic conferred resistance to beta-lactams, gentamicin, and sulfonamide and was transferable by conjugation to P. aeruginosa but not to Escherichia coli. The molecular weight of the purified enzyme was estimated to be 28,000, and the isoelectric point was 9.0. The enzyme showed a broad substrate profile, hydrolyzing imipenem, oxyiminocephalosporins, 7-methoxycephalosporins, and penicillins. The enzyme activity was inhibited by EDTA, iodine, p chloromercuribenzoate, CuSO4, and HgCl2 but not by clavulanic acid or sulbactam. PMID- 1901697 TI - In vitro susceptibilities of ocular Bacillus cereus isolates to clindamycin, gentamicin, and vancomycin alone or in combination. AB - A broth dilution assay was used to determine the in vitro susceptibilities of 10 ocular isolates of Bacillus cereus to clindamycin, gentamicin, and vancomycin both alone and in combination. The checkerboard technique was used to determine fractional inhibitory and bactericidal concentration indices for combinations of clindamycin-gentamicin and vancomycin-gentamicin. PMID- 1901696 TI - Comparison of the activity of cefixime and activities of other oral antibiotics against adult clinical isolates of Moraxella (Branhamella) catarrhalis containing BRO-1 and BRO-2 and Haemophilus influenzae. AB - MICs of 10 oral antibiotics were determined for 105 Moraxella catarrhalis and 96 Haemophilus influenzae isolates from adults. A two- to fourfold increase in MICs of oral cephalosporins was seen in the presence of BRO-1 but not with TEM-1 or BRO-2. The MICs of cefixime for 90% of strains of H. influenzae (0.125 microgram/ml) and M. catarrhalis (0.25 microgram/ml) were 8- to 64-fold lower than those of other oral cephalosporins. PMID- 1901698 TI - In vitro and in vivo activities of LJC10,627, a new carbapenem with stability to dehydropeptidase I. AB - The activity of LJC10,627 was compared with the activities of imipenem and other antibiotics. LJC10,627 was more active against most members of the family Enterobacteriaceae, Pseudomonas spp., and Acinetobacter spp. but slightly less active than imipenem against staphylococci and streptococci. LJC10,627 showed stability to mouse dehydropeptidase I and was more effective in vivo than imipenem plus cilastatin against gram-negative bacterial infections and as effective against staphylococcal infections. PMID- 1901699 TI - Mode of action of netzahualcoyone. AB - The activity of netzahualcoyone on Bacillus subtilis and Escherichia coli was studied. The product inhibited the respiration of intact cells of B. subtilis but had no effect on the respiration of E. coli. However, when preparations of sonically disrupted cells were examined, inhibitory activity on both bacteria was observed. PMID- 1901700 TI - In vitro model of attachment of Giardia intestinalis trophozoites to IEC-6 cells, an intestinal cell line. AB - Attachment of giardias to intestinal cells has been difficult to study because of a lack of a convenient in vitro model. We developed an assay for attachment of radiolabeled trophozoites to IEC-6 cells that can be done in microtiter trays. Attachment was confirmed by scanning and transmission electron microscopy. Trophozoites remained attached to the IEC-6 cells for 24 h with little evidence of damage to the IEC-6 cells. Preincubation of trophozoites with cytochalasins A, B, and D reduced attachment to approximately 20% of that of controls, whereas colchicine had no effect. Chelation of divalent cations with EDTA and EGTA [ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid] reduced attachment to 24 and 26% of control values, respectively, and incubation at 4 degrees C reduced attachment to 7% of the value for controls incubated at 37 degrees C. Glutaraldehyde fixation of trophozoites or IEC-6 cells resulted in significantly diminished attachment to the live substrate (17 and 40% of control values, respectively). Coincubation of IEC-6 cells and trophozoites on a rotary shaker resulted in detachment of 40% of trophozoites, but EDTA, EGTA, glutaraldehyde fixation of trophozoites, and low temperature diminished attachment markedly and significantly. Similar results were obtained in selected experiments with three strains of giardia. PMID- 1901701 TI - Mechanism of action of anticandidal dipeptides containing inhibitors of glucosamine-6-phosphate synthase. AB - The mechanism of anticandidal action of novel synthetic dipeptides containing N3 (4-methoxyfumaroyl)-L-2,3-diaminopropanoic acid (FMDP) residues was shown to be consistent with the "warhead delivery" concept. FMDP dipeptides were shown to be transported into Candida albicans cells by the di-tripeptide permease and subsequently hydrolyzed by intracellular peptidases, especially aminopeptidase. The anticandidal activity of the particular FMDP dipeptide was influenced by the rate of its transport and, to a lower extent, by the intracellular cleavage rate. A high transport rate accompanied by a high cleavage rate resulted in the high anticandidal activity of L-norvalyl-FMDP. The strong growth-inhibitory effect of this compound was the consequence of inhibition of the enzyme glucosamine-6 phosphate synthase by the released FMDP. The action of L-norvalyl-FMDP on exponentially growing C. albicans cells resulted in a sharp decrease of incorporation of 14C label from [14C]glucose into chitin, mannoprotein, and glucan. This effect, as well as the growth-inhibitory effect, was fully reversed by exogenous N-acetyl-D-glucosamine. Glucosamine-6-phosphate synthase was proved to be the only essential target for FMDP dipeptides. Scanning electron microscopy of C. albicans cells treated with L-norvalyl-FMDP revealed highly distorted, wrinkled, and collapsed forms. Cells formed long, bulbous chains, and partial lysis occurred. PMID- 1901702 TI - Cloning and characterization of the isopenicillin N synthase gene of Streptomyces griseus NRRL 3851 and studies of expression and complementation of the cephamycin pathway in Streptomyces clavuligerus. AB - A gene, pcbC, encoding the isopenicillin N synthase of Streptomyces griseus NRRL 3851, has been cloned in a 6.4-kb Bg/II DNA fragment and located in an internal 1.55-kb PvuII segment by hybridization with the Penicillium chrysogenum pcbC gene. Hybridization studies revealed the presence of homologous sequences in the DNAs of several Streptomyces strains and Nocardia lactamdurans. The S. griseus pcbC gene was not expressed in Streptomyces lividans but was expressed in Streptomyces clavuligerus and complemented a mutation, nce2, that impaired isopenicillin N synthase and cephamycin biosynthesis. The pcbC gene contained an open reading frame of 990 nucleotides that encodes a protein of 329 amino acids with a deduced Mr of 37,371. The isopenicillin N synthase formed after expression of the pcbC gene in the S. clavuligerus nce2 mutant strain was found to have an Mr of 38,000 by gel filtration. A protein of about 38 kDa was observed in sodium dodecyl sulfate-polyacrylamide gel electrophoresis gels of extracts of a transformant of the nce2 mutant strain; this protein was absent from the untransformed mutant strain. The G+C content of the pcbC gene was 63.6%, and the strongly biased codon usage was typical of that of Streptomyces strains. A transcription initiation site was found 44 nucleotides upstream of the ATG translation initiation triplet. A transcript of 1.1 kb was observed in the donor S. griseus strain and also in the S. clavuligerus nce2 mutant strain transformed with the pcbC gene, suggesting that it is transcribed as a monocistronic mRNA. PMID- 1901703 TI - In vitro susceptibilities of Coxiella burnetii, Rickettsia rickettsii, and Rickettsia conorii to the fluoroquinolone sparfloxacin. AB - In vitro susceptibilities of Rickettsia rickettsii, Rickettsia conorii, and Coxiella burnetii to the new fluoroquinolone sparfloxacin (AT-4140; RP 64206) were determined. Plaque and dye uptake assays were used to measure the MICs against R. rickettsii and R. conorii. The susceptibilities of C. burnetii Nine Mile and Q 212 were determined in two acute-infection models and in two chronic infection models. The MICs were 0.125 to 0.25 microgram/ml for R. rickettsii and 0.25 to 0.5 microgram/ml for R. conorii. Sparfloxacin (1 microgram/ml) cured cells recently infected with C. burnetii Nine Mile and Q 212 within 4 to 9 days and cured multiplying, persistently infected cells within 10 days. As previously described with other fluoroquinolones (D. Raoult, M. Drancourt, and G. Vestris, Antimicrob. Agents Chemother. 34:1512-1514, 1990), sparfloxacin failed to cure cells persistently infected with C. burnetii and blocked from dividing with cycloheximide. As determined by the dye uptake assay, no cellular toxicity was noted with sparfloxacin at up to 128 micrograms/ml. These results are consistent with those previously obtained with fluoroquinolones (D. Raoult, M. Yeaman, and O. Baca, Rev. Infect. Dis. 11[Suppl. 5]:S986, 1989), although sparfloxacin may be slightly more active. PMID- 1901704 TI - Secretion of TEM beta-lactamase with signal sequences isolated from the chromosome of Lactococcus lactis subsp. lactis. AB - With TEM beta-lactamase as a reporter gene, a set of expression-secretion promoting fragments were isolated from the chromosome of Lactococcus lactis subsp. lactis. The fact that only translocated beta-lactamase renders cells resistant to ampicillin allowed direct ampicillin selection with an Escherichia coli vector (pKTH33). The clones showing the greatest ampicillin resistance were subcloned onto a replicon capable of replication in lactic acid bacteria (pVS2), and the nucleotide sequences of the relevant fragments were determined. The structure of the secretion-promoting fragments in general resembled that of gram positive true signal sequences, with a strongly positively charged N terminus, a long hydrophobic core, and a putative signal peptidase recognition site. The promoterlike sequences preceding the signal sequences matched well with those of previously published lactococcal promoters. In addition to E. coli, the functioning of these expression-secretion cassettes was studied in three gram positive hosts: Bacillus subtilis, L. lactis, and Lactobacillus plantarum. Efficient expression and secretion of TEM beta-lactamase into the culture medium of each gram-positive host was obtained. Furthermore, when a strain of L. lactis subsp. lactis showing increased sensitivity to lysozyme was compared with a standard laboratory strain, threefold-higher secreted enzyme activities were detected. PMID- 1901705 TI - Improved vector for promoter screening in lactococci. AB - Fragments of Lactococcus lactis subsp. lactis NP45 chromosomal DNA provided promoter activity in Escherichia coli when cloned into the promoter probe vector pGKV210. Only 13% of these recombinant plasmids promoted detectable cat-86 activity when transferred to L. lactis, i.e., expressed chloramphenicol resistance. In these promoter-containing versions of pGKV210, the cat-86 gene specifies chloramphenicol-inducible chloramphenicol acetyltransferase expression. This could be a limiting factor for cloning of promoters with lower activity in L. lactis. Therefore, we have constructed a new promoter probe vector, pBV5030, with the mutated version of the cat-86 gene, which is constitutively expressed when transcriptionally activated by the insertion of a promoter. We found that in L. lactis IL1403 the constitutively expressed cat-86 gene (on a pBV5030 derivative) has four times higher activity than the inducible version of the same gene (on a pGKV210 derivative) when both have the same promoter inserted upstream of the cat-86 gene. These results suggest that plasmid pBV5030 could be a more efficient vector for the cloning of promoters from lactococci. PMID- 1901706 TI - Biolistic transformation of a procaryote, Bacillus megaterium. AB - We present a simple and rapid method for introducing exogenous DNA into a bacterium, Bacillus megaterium, utilizing the recently developed biolistic process. A suspension of B. megaterium was spread onto the surface of nonselective medium. Plasmid pUB110 DNA, which contains a gene that confers kanamycin resistance, was precipitated onto tungsten particles. Using a biolistic propulsion system, the coated particles were accelerated at high velocities into the B. megaterium recipient cells. Selection was done by use of an agar overlay containing 50 micrograms of kanamycin per ml. Antibiotic-resistant transformants were recovered from the medium interface after 72 h of incubation, and the recipient strain was shown to contain the delivered plasmid by agarose gel electrophoresis of isolated plasmid DNA. All strains of B. megaterium tested were successfully transformed by this method, although transformation efficiency varied among strains. Physical variables of the biolistic process and biological variables associated with the target cells were optimized, yielding greater than 10(4) transformants per treated plate. This is the first report of the biolistic transformation of a procaryote. PMID- 1901707 TI - Organization and nucleotide sequences of two lactococcal bacteriocin operons. AB - Two distinct regions of the Lactococcus lactis subsp. cremoris 9B4 plasmid p9B4 6, each of which specified bacteriocin production as well as immunity, have been sequenced and analyzed by deletion and frameshift mutation analyses. On a 1.8-kb ScaI-ClaI fragment specifying low antagonistic activity, three open reading frames (ORFs) were present, which were organized in an operon. The first two ORFs, containing 69 and 77 codons, respectively, were involved in bacteriocin activity, whereas the third ORF, containing 154 codons, was essential for immunity. Primer extension analysis indicated the presence of a promoter upstream of the ORFs. Two ORFs were present on a 1.3-kb ScaI-HindII fragment specifying high antagonistic activity. The first ORF, containing 75 codons, specified bacteriocin activity. The second ORF, containing 98 codons, specified immunity. The nucleotide sequences of both fragments upstream of the first ORFs as well as the first 20 bp of the first ORF of both bacteriocin operons appeared to be identical. PMID- 1901708 TI - Genetic construction of nisin-producing Lactococcus lactis subsp. cremoris and analysis of a rapid method for conjugation. AB - Conjugation was used to construct nisin-producing Lactococcus lactis subsp. cremoris strains. Recipients were obtained by electroporation of L. lactis subsp. cremoris strains with the drug resistance plasmid pGK13 or pGB301. A method, direct-plate conjugation, was developed in which donor and recipient cells were concentrated and then combined directly on selective media. This method facilitated transfer of the nisin-sucrose (Nip+ Suc+) phenotype from the donor strain, L. lactis subsp. lactis 11454, to three L. lactis subsp. cremoris recipient strains. Nip+ Suc+ L. lactis subsp. cremoris transconjugants were obtained at frequencies which ranged from 10(-7) to 10(-8) per donor CFU. DNA-DNA hybridization to transconjugant DNAs, performed with an oligonucleotide probe synthesized to detect the nisin precursor gene, showed that this gene was transferred during conjugation but was not associated with detectable plasmid DNA. Further investigation indicated that L. lactis subsp. cremoris Nip+ Suc+ transconjugants retained the recipient strain phenotype with respect to bacteriophage resistance and acid production in milk. Results suggested that it would be feasible to construct nisin-producing L. lactis subsp. cremoris strains for application as mixed and multiple starter systems. Additionally, the direct plate conjugation method required less time than filter or milk agar matings and may also be useful for investigations of conjugal mechanisms in these organisms. PMID- 1901709 TI - Thermosensitive plasmid replication, temperature-sensitive host growth, and chromosomal plasmid integration conferred by Lactococcus lactis subsp. cremoris lactose plasmids in Lactococcus lactis subsp. lactis. AB - Evidence is presented that lactose-fermenting ability (Lac+) in Lactococcus lactis subsp. cremoris AM1, SK11, and ML1 is associated with plasmid DNA, even though these strains are difficult to cure of Lac plasmids. When the Lac plasmids from these strains were introduced into L. lactis subsp. lactis LM0230, they appeared to replicate in a thermosensitive manner; inheritance of the plasmid was less efficient at 32 to 40 degrees C than at 22 degrees C. The stability of the L. lactis subsp. cremoris Lac plasmids in lactococci appeared to be a combination of both host and plasmid functions. Stabilized variants were isolated by growing the cultures at 32 to 40 degrees C; these variants contained the Lac plasmids integrated into the L. lactis subsp. lactis LM0230 chromosome. In addition, the presence of the L. lactis subsp. cremoris Lac plasmids in L. lactis subsp. lactis resulted in a temperature-sensitive growth response; growth of L. lactis subsp. lactis transformants was significantly inhibited at 38 to 40 degrees C, thereby resembling some L. lactis subsp. cremoris strains with respect to temperature sensitivity of growth. PMID- 1901711 TI - Detection of Listeria monocytogenes by direct colony hybridization on hydrophobic grid-membrane filters by using a chromogen-labeled DNA probe. AB - A DNA probe specific for Listeria monocytogenes was isolated from a beta hemolytic recombinant clone of an L. monocytogenes gene bank. It was labeled with horseradish peroxidase and used in a direct colony hybridization method on hydrophobic grid-membrane filters for the detection of the organism. Following color development of the chromogen, a commercial counter (HGMF Interpreter) was able to detect and count the organisms electronically. The method gave a positive reaction with 70 L. monocytogenes strains, while showing a negative reaction with 10 strains of other Listeria spp. and with 20 organisms of other genera. PMID- 1901712 TI - Improved method for coliform verification. AB - Modification of a method for coliform verification presented in Standard Methods for the Examination of Water and Wastewater is described. Modification of the method, which is based on beta-galactosidase production, involves incorporation of a lactose operon inducer in medium upon which presumptive coliform isolates are cultured prior to beta-galactosidase assay. PMID- 1901710 TI - Interactions between Pseudomonas aeruginosa and iodophor germicides in milking parlor udder wash water systems. AB - In a field study of 29 dairy farms, Pseudomonas aeruginosa was isolated more frequently (P = 0.05) from milking parlor udder wash water systems containing iodophor germicides than from those with no germicide. Most available iodine (AI2) concentrations were below the recommended level of 25 ppm (25 microgram/ml). Rubber and polyvinyl chloride hoses caused rapid decreases in the AI2 concentrations of 25 ppm iodophor solutions. AI2 dropped from 25 ppm to 6 ppm or less in 240 min for solutions contained in either polyvinyl chloride or rubber, compared with solutions in glass, which were unchanged in 240 min. Addition of inactivated iodophor solution to aqueous cultures resulted in significantly higher (P less than 0.05) numbers of P. aeruginosa at 10 and 24 h postinoculation. P. aeruginosa was grown in polyvinyl chloride tubing and exposed twice daily to 0, 10, or 25 ppm of AI2. None of the exposure concentrations eliminated the bacteria from the hoses, and bacterial numbers were not significantly different in hoses exposed to 0 and 10 ppm by the eighth treatment day. Bacteria taken from the water in these hoses were exposed to different concentrations of iodophor solution. Iodophor concentrations which will kill 50% of P. aeruginosa cultures previously exposed to 0, 10, and 25 ppm of AI2 were predicted to be 3.0, 11.8, and 20.8 ppm, respectively. PMID- 1901714 TI - [Importance of studying deficiencies of IgG subclasses (IgG2 and IgG4) in immuno allergologic practice]. AB - Levels of the sub-classes of immunoglobulins IgG2 and IgG4 have been established by radial diffusion with monoclonal antibodies in 150 subjects. 49 (42 adults and 7 children) showed either a low level of IgG2 (less than 0.42 g/l n = 11) or a reduced level of IgG4 (less than 0.05 g/l n = 38). A single patient had a double deficit, 38 subjects had a superinfection of which 17 had a severe form and in 77% of these cases a level of IgG4 of less than 0.05 g/l. PMID- 1901713 TI - Species-specific detection of Listeria monocytogenes by DNA amplification. AB - The polymerase chain reaction was used to detect and specifically identify Listeria monocytogenes. A 174-bp region of the listeriolysin O gene was shown to be specifically amplified in L. monocytogenes but not in other species of Listeria or in a number of other gram-positive and gram-negative organisms. Less than 50 organisms could routinely be detected by a procedure involving two rounds of 35 amplification cycles each and without the need for subsequent hybridization with labeled probes. PMID- 1901715 TI - Genetic and molecular analysis of maternal information in region 32 of Drosophila melanogaster. PMID- 1901716 TI - Neuronal determination without cell division in Xenopus embryos. AB - Cell division in the Xenopus CNS was blocked by incubating embryos in a mixture of the DNA synthesis inhibitors hydroxyurea and aphidicolin. Surprisingly, embryos treated at the beginning of gastrulation proceeded normally through neurulation, neural tube closure, and CNS subdivision. Thus, cell division is not critical for neural induction or early morphogenetic events in the CNS. Neuroblasts in treated embryos differentiated into neurons of many classes, indicating that cellular determination in the CNS can be dissociated from lineage and birth date. Axonal tracts and embryonic reflexes also developed. The remarkable amount of normal CNS development that occurs in these animals may be explained by a series of sequential inductions that are largely independent of cell proliferation. PMID- 1901717 TI - Modulation of M-current by intracellular Ca2+. AB - IM is a voltage- and time-dependent K+ current that is suppressed by muscarinic receptor activation. IM augmentation following agonist washout was blocked by heavily buffering [Ca2+]i using BAPTA. Although IM is not primarily Ca2+ dependent, small increases in [Ca2+]i by photolysis of the "caged" Ca2+ chelator nitr-5 or by evoking action potentials augmented, while larger increases inhibited, IM. Raising [Ca2+]i for prolonged periods, by nitr-5 photolysis, reduced its sensitivity to agonist, leaving a poorly reversible response. These results suggest that IM can be regulated by physiologically relevant changes in [Ca2+]i, placing IM in a unique position to modulate cell excitability. PMID- 1901718 TI - Molecular pathways of pain: Fos/Jun-mediated activation of a noncanonical AP-1 site in the prodynorphin gene. AB - Noxious stimulation provokes the activation of genes that are thought to play a crucial role in the phenomena of stress and pain. Among these is the prodynorphin gene. By double-labeling in situ hybridization/immunohistochemistry, we show that increased prodynorphin gene expression is preceded, in the same neurons, by an early induction of c-fos. Inspection of the prodynorphin promoter region revealed the presence of several AP-1-like sequences. We demonstrate that only one of these sites is a functional AP-1 element. It is constituted by the noncanonical TGACAAACA sequence, in which the palindromic structure is partly conserved by the 3' terminal CA dinucleotide. Transfection experiments in NCB20 neuroblastoma cells indicated that this site is a target of Fos/Jun trans-activation. Our results suggest that Fos/Jun oncoproteins may function as third messengers in the signal transduction mechanisms of stress/pain processes. PMID- 1901719 TI - Augmentation of superoxide dismutase and catalase activity in alveolar type II cells. AB - This study tested whether adducts formed by covalent linkage of superoxide dismutase (SOD) or catalase to polyethylene glycol (PEG) could augment SOD and catalase activity in alveolar type II cells and document enhanced resistance to oxidant damage. Alveolar type II cells were isolated from adult, pathogen-free rats. Antioxidant enzymes were added to the medium of cell cultures in various concentrations for periods up to 48 h. Incubation with 500 to 3,000 U of PEG-SOD or 10,000 to 40,000 U of PEG-catalase/10(6) cells produced a dose-response related increase in intracellular enzyme activity in comparison with controls (untreated or treated with SOD or catalase, inactivated PEG-SOD or PEG-catalase, or PEG alone). Uptake was maximal during the first 4 h. Using fluorescent label (fluorescein isothiocyanate) bound to PEG-catalase, we found intracellular localization of the labeled enzyme. Exposure to H2O2 led to reduced cytotoxicity in cells pretreated with PEG-catalase than in controls. We conclude that supplementation with PEG-SOD or PEG-catalase enhanced the activity of these enzymes in alveolar type II cells and increased their resistance to oxidant stress. PMID- 1901720 TI - Endogenous arachidonic acid metabolism by calcium ionophore A23187-stimulated lamb lungs: effect of hypoxia. AB - We have determined eicosanoid production from endogenous arachidonic acid by neonatal lamb lungs stimulated with calcium ionophore A23187 during normoxia and hypoxia. Lungs of lambs 19 to 25 d of age were isolated and perfused with cell free Krebs' bicarbonate buffer at a flow rate of 15 to 20 ml/kg/min. After 30 min of equilibration in a recirculating system, A23187 was added to the perfusate in a 5-microM concentration and perfusion continued for 15 min more. Eicosanoids were measured in perfusate and lung homogenate supernatant. Cyclooxygenase metabolites prostaglandin (PG) E2, thromboxane A2, and PGI2, were measured by radioimmunoassay, and 5-lipoxygenase metabolites leukotrienes (LT) B4, C4, D4, and E4 by high performance liquid chromatography. During normoxia, all three cyclooxygenase metabolites were present in perfusate, but only PGI2 and thromboxane A2 were present in lung homogenate supernatant. Prostacyclin constituted 50% of all the cyclooxygenase products measured. LTC4 and LTD4 were detected in both perfusate and lung homogenate supernatant with little production of LTE4 and LTB4. During hypoxia, the profile of cyclooxygenase products was unchanged and prostacyclin production was not increased. However, the profile of leukotriene metabolites was altered. LTC4 synthesis was markedly reduced. The synthesis of LTE4 and LTB4 was increased 10-fold, with most of the leukotrienes being retained in lung tissue. We conclude that hypoxia significantly alters leukotriene metabolism of endogenous arachidonic acid by calcium ionophore stimulated lungs. The increased production by stimulated lungs during hypoxia of LTE4, a substance that may increase lung capillary permeability, and that of LTB4, a powerful chemoattractant, may be important contributing factors to lung injury. PMID- 1901721 TI - Highly immunogenic human immunodeficiency viruslike particles are produced by recombinant vaccinia virus-infected cells. AB - CV-1 cells were infected with two recombinant vaccinia viruses carrying the gag gene with deletion of 231 bp from 3' terminus (strain vC5) and env gene (strain vE234L) of human immunodeficiency virus type 1 (HIV-1). Both recombinant proteins synthesized in the cells (p50gag and gp160/120env) were localized predominantly in cell membranes; however, some amount of p50 was found in cell nuclei. Thin section immunoelectron microscopy showed accumulation of viruslike particles undistinguished from immature HIV-1 virions in the culture medium of the cells infected with vC5. The similar particles containing gag and env proteins were produced into the culture medium when the cells were coinfected with vC5 and vE234L strains. The particles contained heterogeneous cellular RNA, but no virus specific RNA as shown by Northern blot hybridization. Immunization of the rabbits with purified viruslike particles produced virus-specific antibodies against gag and env proteins. The titer of antibodies was significantly higher than after immunization with cell lysate or recombinant proteins purified from the infected cells. Highly immunogenic HIV-1-like particles containing gag and env proteins but no virus-specific RNA are good candidates for potential vaccine. PMID- 1901722 TI - Blood conservation. PMID- 1901723 TI - Viability and distribution of bacteria after passage through a circle anaesthetic system. AB - We have assessed in vitro the viability of eight species of micro-organism suspended as aerosols and passed through a soda-lime absorber rebreathing system. As had been predicted, the soda-lime exerted a potent cidal effect on non-sporing organisms, all of which were rendered non-viable. One percent of the spore bearing organism, Bacillus subtilis, was still viable after 30 min contact. Although Bacillus subtilis is an organism of low pathogenicity, spores may be more resistant to the alkaline medium of the soda-lime. The micro-organisms were observed to lodge in all components of the breathing system, with the greatest concentration being recovered from the corrugated tubing. We recommend that disposable components of the circle breathing system should be changed, and the non-disposable parts sterilized or disinfected, daily. Soda-lime cannisters should be sterilized or disinfected when changing the soda-lime. PMID- 1901724 TI - Is the end-tidal partial pressure of isoflurane a good predictor of its arterial partial pressure? AB - End-tidal partial pressure of isoflurane (PE'iso) may be used as a measure of anaesthetic depth. During uptake, an arterial partial pressure (Paiso) which is considerably less than PE'iso (Paiso/PE'iso much less than 1) leads to underestimation of depth of anaesthesia and, during elimination, PE'iso/Paiso much less than 1 will lead to an overestimation of anaesthetic depth. We measured Paiso/PE'iso during a 60-min uptake period of 1% isoflurane and PE'iso/Paiso during the subsequent 60-min elimination period in 26 patients (age 13-88 yr, ASA I-III) undergoing various surgical procedures. After 15 min of isoflurane uptake, Paiso/PE'iso of 26 patients was mean 0.78 (SD 0.10) and this increased only marginally at 60 min (0.79 (0.09)), whereas during elimination, PE'iso/Paiso was in the range 0.79 (0.14)-0.83 (0.11). Predictability of Paiso in a given patient is hindered by the high SD of Paiso/PE'iso and PE'iso/Paiso, but it may be improved by taking into account age, ASA physical status category, vital capacity, inspired minus end-tidal isoflurane partial pressure and arterial minus end-tidal carbon dioxide partial pressure during uptake; and obesity, end-tidal isoflurane partial pressure and arterial minus end-tidal carbon dioxide partial pressure during elimination. However, even with multiple regression analysis (to account for the various possible variables), clinically useful prediction of Paiso/PE'iso and PE'iso/Paiso in a particular patient is not possible (residual SD 0.084 and 0.113, respectively). PMID- 1901725 TI - Bilateral chylothorax. AB - A 2.5-kg female developed bilateral chylothoraces 10 days after surgery for coarctation of the aorta. Initial conservative management consisted of intermittent positive pressure ventilation, drainage of chylous fluid and enteral feeding, but there was no diminution in loss of chyle. Ligation of the thoracic duct and pleurectomy were performed subsequently to reduce the large daily losses of chyle, amounting to nearly three times the child's circulating blood volume. Brawny oedema of the right upper quadrant of the body developed rapidly after the duct ligation and right pleurectomy. A further period of conservative treatment was required before the latter complication resolved. The literature relating to this iatrogenic complication and to fluid and nutritional losses in paediatric chylothorax is reviewed and discussed. PMID- 1901726 TI - Guanine nucleotide dependent formation of a complex between choleragen (cholera toxin) a subunit and bovine brain ADP-ribosylation factor. AB - Cholera toxin activates adenylyl cyclase by catalyzing the ADP-ribosylation of Gs alpha, the stimulatory guanine nucleotide binding protein of the cyclase system. This toxin-catalyzed reaction, as well as the ADP-ribosylation of guanidino compounds and auto-ADP-ribosylation of the toxin A1 protein (CTA1), is stimulated, in the presence of GTP (or GTP analogue), by 19-21-kDa proteins, termed ADP-ribosylation factors or ARFs. These proteins directly activate CTA1 in a reaction enhanced by sodium dodecyl sulfate (SDS) or dimyristoylphosphatidylcholine (DMPC)/cholate. To determine whether ARF stimulation of ADP-ribosylation is associated with formation of a toxin-ARF complex, these proteins were incubated with guanine nucleotides and/or detergents and then subjected to gel permeation chromatography. An active ARF-toxin complex was observed in the presence of SDS and GTP gamma S [guanosine 5'-O-(3 thiotriphosphate)] but not GDP beta S [guanosine 5'-O-(2-thiodiphosphate)]. Only a fraction of the ARF was capable of complex formation. The substrate specificities of complexed and noncomplexed CTA differed; complexed CTA exhibited markedly enhanced auto-ADP-ribosylation. In the presence of GTP gamma S and DMPC/cholate, an ARF-CTA complex was not detected. A GTP gamma S-dependent ARF aggregate was observed, however, exhibiting a different substrate specificity from monomeric ARF. These studies support the hypothesis that in the presence of guanine nucleotide and either SDS or DMPC/cholate, ARF and toxin exist as multiple species which exhibit different substrate specificities. PMID- 1901727 TI - Hospital use by adolescents and young adults. AB - This article provides a descriptive profile of hospital use by adolescents (10-14 and 15-18 years of age) and young adults (19-24 years) based on the 1987 National Hospital Discharge Survey. During 1987, nearly 5 million adolescents and young adult patients were discharged from short-stay hospitals. The discharge rate for adolescents was 56.5 per 1000 compared to 127.0 per 1000 for young adults. Two diagnostic categories--complications of pregnancy, childbirth, and the puerperium; and injury and poisoning--together accounted for 24% of discharges for patients aged 10-14 years, 51% for patients aged 15-18 years, and 65% for patients aged 19-24 years. Average length of stay varied substantially by age and diagnosis; that for adolescents averaged 1.1 days longer than that for young adults and for other age groups and was longest for mental disorders. Between 1980-1981 and 1986-1987, the rates of hospitalization for mental disorders increased markedly, particularly among adolescents aged 15-18 years with the diagnoses of adjustment reaction and disturbance of conduct, and psychosis, neurosis, and personality disorders. Hospitalizations for substance abuse increased most among young adults during this time period. Most adolescents and young adults relied on private health insurance as their primary payment source, followed by Medicaid. Still, there was no insurance coverage to pay for hospital bills for 729,000 discharges in 1987. Implications of these findings are discussed. Briefly, examining hospitalization patterns by narrower age intervals elucidates important differences by age, sex, diagnostic category, and expected source of payment. PMID- 1901728 TI - Zinc binding in intestinal brush-border membrane isolated from pig. AB - Zinc binding to brush-border membrane vesicles isolated from pig jejunum was investigated by a rapid filtration method, for long incubation periods (up to 180 min). Zn2+ influx revealed a large accumulation of the metal, reaching an apparent intravesicular volume of 160 microliters/mg protein at equilibrium, a volume 45-times that of an osmotically reactive sugar, sorbitol (3.6 microliters/mg protein). Changes in medium osmolarity had no effect on zinc accumulation. These results suggested a large degree of zinc binding to vesicular components (membrane or core). 65Zn efflux measurements led to the conclusion that two vesicular pools of zinc existed: a small external pool, accessible to different chelators (EGTA) or competitive cations, and a large intravesicular pool. Accumulated 65Zn was quickly removed from its internal sites only after the membrane had been permeabilized by the cation ionophore A23187 in association with an exchange molecule or a chelator. Scatchard plot analyses revealed, on one hand a first class of high-affinity extravesicular zinc binding sites (Ka = 8.6.10(3) M-1, n = 0.455 nmol Zn2+/mg protein) and a second class of extravesicular sites having a very low affinity (Ka = 22 M-1, n = 25.35 nmol Zn2+/mg protein) and, on the other hand one type of intravesicular sites (Ka = 3.3.10(4) M-1, n = 550 nmol Zn2+/mg protein). The intravesicular sites have a high affinity for zinc and are specific, since only nonlabelled zinc (or cadmium) but not calcium present in the bathing medium is exchanged with the internally accumulated labelled cation. PMID- 1901729 TI - Phosphorylase b kinase and phosphorylase a phosphatase activities in contracting vascular smooth muscle: stimulation by fatty acid. AB - The activities of phosphorylase b kinase and phosphorylase a phosphatase were determined during the phases of KCl-induced contraction in porcine carotid artery. Phosphorylase b kinase exhibited a biphasic pattern with activity increasing 70% above basal levels during the early phase of active force generation (45 s into contraction) followed by a decline in activity during the phase of steady-state tension maintenance. Phosphorylase a phosphatase was stimulated simultaneously with phosphorylase b kinase, with activity increasing 100% over basal levels at 45 s into contraction, but remaining elevated at 30 min. Incubation of arteries in 0.5 mM palmitate resulted in a 30% increase in basal activity of phosphorylase b kinase and 117% augmentation of basal phosphatase activity, with no further increase in activity of either enzyme with contraction. The results indicate that both the kinase and phosphatase are subject to regulation during contractile activation of the muscle, possibly by similar but not identical mechanisms. PMID- 1901730 TI - 4-Aminobutyrate aminotransferase: identification of lysine residues connected with catalytic activity. AB - Bis-PLP (P'P2-bis[5'-pyridoxal]diphosphate) was used as a probe of the catalytic site of 4-aminobutyrate aminotransferase. It reacts with lysine residues connected with aminotransferase activity and the binding of 1 mol of reduced bis PLP/enzyme monomer abrogates catalytic activity. The reactive lysine residues are characterized by low pK values (pK = 7.3). The presence of substrate 2 oxoglutarate (4 mM) prevents inactivation of the aminotransferase treated with bis-PLP. After tryptic digestion of the enzyme modified with bis-PLP and reduced with tritiated NaBH4, a radioactive peptide absorbing at 320 nm was separated by reverse-phase high-performance liquid chromatography. The amino acid sequence of the radioactive peptide, elucidated by Edman degradation, revealed that a specific lysine residue of monomeric 4-aminobutyrate aminotransferase has reacted with bis-PLP. The sequence of the modified peptide differs from the sequence of the peptide bearing the cofactor pyridoxal-5-P covalently attached to a lysine residue. It is postulated that the modified lysine residue is involved in direct interactions with negatively charged carboxylic groups of 2-oxoglutarate. PMID- 1901731 TI - Fluctuation of gene expression for poly(ADP-ribose) synthetase during hemin induced erythroid differentiation of human leukemia K562 cells and its reversion process. AB - We have studied the regulation of gene expression for poly(ADP-ribose) synthetase during erythroid differentiation and its reversion process. When human leukemia K562 cells were incubated in the presence of 80 microM hemin, benzidine-positive cells appeared at day 2 and 90% of the cells became positive at day 6. However, RNA blot analysis reveals that mRNA for gamma-globin was already abundant in untreated K562 cells and the level of the message was slightly increased by hemin treatment. Spectroscopic analysis and polyacrylamide gel electrophoresis of the induced cell extracts indicate that hemoglobin molecules were not detected in untreated cells, and increased successively up to day 6. The hemin-induced cells were thoroughly washed, and then recultured in the absence of hemin. The benzidine-positive cells mostly disappeared 3 days after the elimination of the inducer. During the hemin-induced erythroid differentiation, the activity and mRNA for poly(ADP-ribose) synthetase decreased to 50% and 20% of the initial level at day 3 and a low level of the gene expression was maintained afterwards, whereas the activity and mRNA returned to the initial value 1 day after hemin elimination. The results indicate that the hemin-induced erythroid differentiation of K562 cells is a reversible process and depression of the synthetase may be involved in the progress of differentiation. PMID- 1901732 TI - Developmental changes in plasma apolipoproteins B and A-I in fetal bovines. AB - Plasma lipid, apolipoprotein (apo) B and apo A-I concentrations were measured in fetal calves in the age range of 4-9 months. The results were compared with those obtained from preruminant calves and cows. The studied lipids and apolipoproteins underwent quantitative underwent quantitative changes during development. Fetal calves, as compared to preruminant calves and cows, had a particularly low apo A I concentration and a high apo B/apo A-I ratio. Unlike adult animals which have two forms of apo B, fetal calves had only high molecular weight apo B (apo Bh). During fetal development triglyceride, cholesterol and apo B concentrations decreased, but apo A-I concentrations remained constant. PMID- 1901733 TI - Detection of growth-stimulating activity in the proximal small intestine during weaning in the suckling rat. AB - Adaptive changes in enzyme expression and cell proliferation occur in the small intestine of the suckling rat at the beginning of the 3rd postnatal week. This physiological adaptation can be modulated by factors including diet or glucocorticoids. We have previously described an intestinal growth-stimulating fraction derived from the remnant small bowel after resection and found that enteral nutrition is critical for its detection. In view of the similarity between the changes in cell proliferation that occur between 15 and 22 days postnatally and those immediately after resection, we sought to determine whether the small intestinal mucosa of the neonatal rat also contains a similar growth stimulating fraction. Our results show that extracts of the proximal intestine prepared from 15-day-old rats do contain the growth-stimulating fraction. The activity was not detectable in maternal milk nor in the intestinal extract from 8 day-old rats. When the suckling rats were deprived of solid food, the activity was not detectable in the 15-day-old group. Gel filtration of the acidic extract on a G-25 Sephadex column revealed that the active component is made up of two molecular weight species (approximately 4,500 and 1,500 daltons) similar to that described in the proximal intestine of the postresectional model. These findings suggest that dietary factors may play a role in modulating the proliferative changes that occur at the time of weaning by way of the growth-stimulating fraction. PMID- 1901735 TI - Hyperfunctional G proteins in mononuclear leukocytes of patients with mania. AB - In a recent study, we found that lithium inhibits the function of guanine nucleotide-binding proteins, implicating G proteins as the common site for both the antimanic and antidepressant therapeutic effects of lithium. These findings may also suggest that an altered G protein function is of pathophysiological importance in bipolar affective disorder. In the present study, the coupling of both muscarinic-cholinergic receptors and beta-adrenergic receptors to pertussis toxin-sensitive G proteins or cholera toxin-sensitive G proteins was compared among untreated manic patients, lithium-treated euthymic bipolar patients, and healthy volunteers using mononuclear leukocyte (MNL) membrane preparations. Hyperactive function of G proteins was detected in untreated manic patients. Both isoproterenol-induced and carbamylcholine-induced increases in Gpp(NH)p binding capacity were twofold to threefold higher than the increases observed in healthy volunteers. On the other hand, lithium-treated euthymic bipolar patients showed G protein responses to agonist activation that were no different from the healthy volunteers. Altered G protein function may be of pathophysiological importance in bipolar affective disorder. PMID- 1901734 TI - Preferential utilization of lactate in neonatal dog brain: in vivo and in vitro proton NMR study. AB - In vivo proton nuclear magnetic resonance spectroscopy was utilized to determine whether lactate is preferentially utilized as metabolic fuel by the neonatal dog brain. The data showed that during lactate influx, metabolism of lactate could account for most of the fuel needed for oxidative metabolism. The in vivo nuclear magnetic resonance measurements were corroborated by conventional arteriovenous determinations which showed steep decline of arteriovenous difference of glucose and sharp increase in arteriovenous difference of lactate during lactate infusion. PMID- 1901736 TI - Effects of gonadal steroids on follicle-stimulating hormone and luteinizing hormone secretion by pituitary cells from castrated and intact male rats. AB - The effectiveness of androgens in suppressing gonadotropin secretion declines with time following orchidectomy; however, the mechanism for this acquired resistance to androgen action is unknown. The role of the pituitary was studied by use of perifused rat pituitary cells and cells in monolayer culture. Pituitary cells from 7-wk-old intact male rats and rats that had been castrated 2 wk previously were treated with 10 nM testosterone (T) for 24 h; cells were then packed into perifusion chambers and stimulated with 2.5 nM GnRH for 2 min every hour for 8 h during which time T treatment was continued. T suppressed GnRH stimulated LH secretion and LH pulse amplitude equally in both groups to approximately 60% of control values. Interpulse LH secretion was unchanged by T in either group. GnRH-stimulated FSH release was suppressed more (p less than 0.05) by T with cells from castrated rats than with cells from intact rats (76 +/ 4% vs. 90 +/- 2% of control; mean +/- SEM). By contrast, the action of T to increase interpulse basal FSH secretion was less (p less than 0.05) with cells from castrated rats (115 +/- 10% of control) than with cells from intact rats (146 +/- 6% of control). T treatment for 72 h also increased basal FSH secretion by pituitary cells in monolayer culture to a lesser extent with cells from castrated rats than with cells from intact rats (151 +/- 14% vs. 191 +/- 16% of control, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1901737 TI - Endocrine response in rabbits immunized with native versus deglycosylated porcine zona pellucida antigens. AB - Previous studies evaluating porcine zona pellucida antigens for immunocontraceptive purposes have in some cases revealed altered ovarian function in association with antibody response. This study was undertaken in an attempt to identify zona immunogens that do not cause adverse endocrine effects. To this end, we investigated the effects of highly purified preparations of native and deglycosylated pig zona pellucida antigens on ovarian function and immune response in the rabbit. Thirty female rabbits were immunized, 5 per group, with 100 micrograms each of either 1) SIZP, solubilized isolated zonae pellucidae; 2) ZP3, a purified porcine zona preparation containing the two principle glycoproteins, ZP3 alpha and ZP3 beta, endo-beta-galactosidase-digested ZP3 glycoproteins (approximately 30% deglycosylated) termed 3) ZP3 alpha/EBGD and 4) ZP3 beta/EBGD; and chemically deglycosylated ZP3 alpha and ZP3 beta (greater than or equal to 92% deglycosylated), termed 5) ZP3 alpha/DG and 6) ZP3 beta/DG. Rabbits injected with saline (n = 2) or Freund's adjuvant alone (n = 3) served as controls. Serum LH, FSH, estradiol, and progesterone were measured at 5-day intervals during seven 20-day cycles of hCG-induced pseudopregnancy over 42 wk. Anti-ZP3 titers, determined by RIA, developed in all treatment groups and correlated directly with carbohydrate content. Animals immunized with SIZP, ZP3, and ZP3 beta/EBGD showed a significant elevation of LH and FSH and a significant decline of peak progesterone levels by the fourth pseudopregnancy cycle. In contrast, animals immunized with ZP3 alpha/EBGD, ZP3 alpha/DG, and ZP3 beta/DG showed no significant elevations of gonadotropins and continued to display cyclic progesterone secretion in response to hCG.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1901738 TI - Circulating immunoreactive inhibin, gonadotropin, and prolactin levels during pregnancy, lactation, and postweaning estrous cycle in the rat. AB - Serum inhibin levels were measured by heterologous RIA during pregnancy, lactation, and the post-weaning estrous cycle in the rat and correlated with changes in serum FSH and LH and prolactin. Blood was serially collected by cardiac puncture under light ether anesthesia from adult Sprague-Dawley rats on alternate days throughout the experimental period. For the first 8 days of pregnancy, immunoreactive inhibin levels remained high, then gradually decreased to reach a nadir at Day 16, and subsequently rose steeply until parturition. The pattern of serum immunoreactive inhibin levels during early pregnancy does not support a corpus luteum source and the dramatic rise from Day 16 to Day 22 correlates with the recommencement of follicular development in the ovary. Inhibin levels decreased rapidly on the day after birth and were suppressed until Day 8 of lactation, slowly increasing thereafter to reach a plateau from Day 14 until weaning (Day 22.5 of lactation). These changes in inhibin levels positively correlated with LH and FSH and negatively with prolactin, and are consistent with an ovarian source for inhibin associated with the recommencement of follicular development resulting from the diminution of the suckling stimulus. Immediately after weaning, serum immunoreactive inhibin levels showed a 4-day cyclic pattern corresponding to the estrous cycle identified by vaginal smear. Inhibin levels peaked on the day of proestrus, reached a nadir on the day of estrus, and rose slowly during metestrus and diestrus to a new peak at proestrus. Serum FSH levels showed an inverse correlation to inhibin levels consistent with a feedback relationship with inhibin. PMID- 1901739 TI - Starvation-induced suppression of pituitary-testicular function in rats is reversed by pulsatile gonadotropin-releasing hormone substitution. AB - This study was carried out to test the hypothesis that reduced hypothalamic GnRH release is responsible for the suppression of reproductive functions during starvation. Adult male rats were kept for 4 days under total fasting (only water allowed) and injected during this time at 2-h intervals with 100 or 500 ng/kg BW of GnRH or vehicle. Serum levels of LH and FSH decreased by 30% during starvation (p less than 0.05), and these effects were fully reversed by either dose of GnRH treatment. Starvation reduced the pituitary mRNA contents of the gonadotropin common alpha- and FSH beta-subunits by 30% and 35% in starved animals (p less than 0.05 for both), but the LH beta-subunit mRNA was unaffected. The GnRH treatments partly or totally reversed these changes, but up-regulation of the mRNA levels by GnRH was seen only in controls fed ad libitum. Starvation reduced the testicular and serum levels of testosterone by 84% (p less than 0.01) and 42% (p less than 0.05), respectively. These changes were fully reversed by the 500 ng/kg dose of GnRH treatment during fasting, but only serum T was completely reversed by the 100-ng/kg GnRH treatment. To elucidate whether fasting per se had direct effects at the gonadal level, we blocked the secretion of gonadotropins by treatment with a GnRH antagonist, and replaced the gonadotropins by injecting of hCG (10 IU/kg BW once daily) and hFSH (75 IU/kg BW once daily). No differences were observed between starved and control animals in either testicular or serum levels of T, or in accessory sex gland weights.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1901740 TI - Puberty in the male chimpanzee: time-related variations in luteinizing hormone, follicle-stimulating hormone, and testosterone. AB - The onset of pubertal testicular growth (Po) occurred in 12 out of 20 male chimpanzees surveyed monthly for at least 3.7 yr. When animals were synchronized according to Po, the mean weight gain was found to be higher before than after Po, and testicular volume started to rise immediately after Po. The earlier significant hormonal events were a rapid rise in LH and a slight testosterone increase occurring 6 mo before Po. Thereafter, the levels of LH remained elevated while testosterone continued to rise in parallel with the testicular volume. FSH levels increased suddenly at Po, 6 mo after the LH increase. FSH remained elevated for only 9 mo, then dropped to prepubertal levels. The dissociation between onsets of pubertal increases in LH and FSH secretions suggests that the complete reawakening of the hypothalamic-pituitary unit lasts several months. The secondary drop of FSH, occurring at the time of spermarche, may be induced by factor(s) secreted by the testis. PMID- 1901741 TI - Differential steroid and gonadotropin response by individual tertiary porcine follicles in vitro. Possible physiologic role of atretic follicles. AB - Since atretic follicles contain significant amounts of androgen and/or progesterone in their follicular fluid, we examined whether they also contribute to ovarian steroid secretion. Steroid secretion by atretic porcine follicles and their responsiveness to FSH was assessed by a perifusion system that allows for separate dynamic incubation of whole follicles in vitro. Identically treated nonatretic follicles of comparable size served as a reference group. The extent of granulosal pyknosis, on which the staging of atresia was based, was inversely related to follicular estradiol (E2) secretion and its responsiveness to FSH. Both basal and FSH-stimulated secretion of testosterone (T), androstenedione (A), and progesterone (P) were maintained by follicles in all stages of atresia. Secretion of A by late atretic follicles was greater than that in earlier stages or by nonatretic follicles. Atretic follicles may therefore release comparable or larger amounts of androgen and P into their intraovarian environment than do nonatretic follicles. We examined whether steroids secreted by atretic follicles in vitro could be utilized by nonatretic follicles. A static incubation system was used that allows for simultaneous incubation of a number of individual follicles. When nonatretic follicles were exposed to A, T, or P in physiologic concentrations (10(-7)-10(-5) M), their secretion of E2 increased 2-8-fold. Doses of FSH or LH that stimulated follicular steroid in vitro had no additional stimulatory effect when combined with A or P treatment, respectively. In conclusion, atretic follicles may contribute significantly to intraovarian levels of androgen and P.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1901742 TI - Follicle-stimulating hormone pulse amplitude decreases with the onset of the breeding season in the mare. AB - The relationship between daily mean FSH concentrations in serum and the pattern of FSH detected by frequent sampling for 12-h periods (samples every 15 min) was examined in five mares during the transition into the breeding season. The five mature anestrous mares were exposed to a natural increase in daylength. Blood samples were collected daily from February 1 until the first ovulation of the breeding season (April 14 +/- 3.7 days, Mean +/- SEM). Periods of frequent blood collection were performed every two weeks. Blood samples were obtained daily by jugular venipuncture or jugular cannula (frequent samples). Mean daily concentrations of FSH in serum determined by RIA decreased during seasonal transition. Patterns of FSH in serum detected by frequent sampling were pulsatile. FSH pulse amplitude decreased during seasonal transition, and the decrease in amplitude was associated with the decrease in mean serum FSH concentrations. This decrease in FSH pulse amplitude may reflect an involvement of a follicular product from developing follicles or a change in hypothalamic stimulation of pituitary FSH release. PMID- 1901743 TI - A voltage-dependent gap junction in Drosophila melanogaster. AB - Steady-state and kinetic analyses of gap junctional conductance, gi, in salivary glands of Drosophila melanogaster third instar larvae reveal a strong and complex voltage dependence that can be elicited by two types of voltages. Voltages applied between the cells, i.e., transjunctional voltages, Vj, and those applied between the cytoplasm and the extracellular space, inside-outside voltages, Vi,o, markedly alter gj. Alteration of Vi-o while holding Vj = O,i.e., by equal displacement of the voltages in the cells, causes gj to increase to a maximum on hyperpolarization and to decrease to near zero on depolarization. These conductance changes associated with Vi-o are fit by a model in which there are two independent gates in series, one in each series, one in each membrane, where each gate is equally sensitive to Vi-o and exhibits first order kinetics. Vj's generated by applying voltage steps of either polarity to either cell, substantially reduce gj. These conductance changes exhibit complex kinetics that depend on Vi-o as well as Vj. At more positive Vi-o's, the changes in gj have two phases, an early phase consisting of of a decrease in gj for either polarity of Vj and a later phase consisting of an increase in gj on hyperpolarizing either cell and a decrease on depolarizing either cell. At negative Vi-o's in the plateau region of the gj-Vi-o relation, the later slow increase in gj is absent on hyperpolarizing either cell. Also, the early decrease in gj for either polarity of Vj is faster the more positive the Vi-o. The complex time course elicited by applying voltage steps to one cell can be explained as combined actions of Vi-o and Vj, with the early phase ascribable to Vj, but influenced by Vi-o, and the later phase to the changes in Vi-o associated with the generation of Vj. The substantially different kinetics and sensitivity of changes in gj by Vi-o and Vj suggests that the mechanisms of gating by these two voltages are different. Evidently, these gap-junction channels are capable of two distinct, but interactive forms of voltage dependence. PMID- 1901745 TI - Monoclonal antibodies against leukemic hairy cells that also recognize T-cell activation antigens. PMID- 1901744 TI - Predominant T cell receptor V gene usage in patients with abnormal clones of B cells. AB - We have examined alpha/beta V gene segment usage of peripheral blood CD4+ and CD8+ T cells, respectively, from patients with multiple myeloma and monoclonal gammopathy of undetermined significance, by using T cell receptor (TCR) for antigen monoclonal antibodies (MoAbs). In 7 of 16 patients we found an increase in the usage of various TCR V gene segments. The expansion was confined to either the CD4+ or the CD8+ T-cell subset, except for one patient where an abnormal pattern was observed both within the CD4+ and CD8+ T-cell subsets. In one patient 47%, and in another patient 30% of the CD8+ lymphocytes reacted with alpha V12.1 and beta V6.7 antibodies, respectively. In two other patients 29% and 40% of the CD4+ lymphocytes reacted with beta V6.7 and beta V8.1 antibodies, respectively. We conclude that T cells with a predominant V gene usage is a frequent feature in patients with abnormal clonal B cells of malignant or benign types. T- and B-cell populations are normally clonally linked in regulatory circuits. An abnormal proliferation of B cells might therefore induce, or be regulated by, an expansion of clonal T cells, as suggested by the present results. PMID- 1901746 TI - B-ly-7, a monoclonal antibody labeling of activated lung lymphocytes. PMID- 1901747 TI - Effect of thyrotropin releasing hormone (TRH) on acetylcholine release from different brain areas investigated by microdialysis. AB - 1. The effect of thyrotropin releasing hormone (TRH) administration upon acetylcholine (ACh) release in freely moving rats was investigated by means of transversal microdialysis coupled to h.p.l.c. TRH administered either s.c. or via local perfusion increased the ACh release from cortex and hippocampus but not from the striatum. The increase in ACh release was maintained after 7 days of s.c. administration of TRH. 2. After s.c. injection of the neuropeptide, the increase in ACh release was dose-dependent and reached a maximum at 40 min after administration. The maximal percentage increases were 18, 52, 66 and 89% at doses of 1, 2.5, 5 and 10 mg kg-1 and 35, 48 and 54% at doses of 2.5, 5 and 10 mg kg-1 in the cortex and hippocampus, respectively. The effect of TRH was dependent on neuronal activity since it was completely inhibited by perfusion with tetrodotoxin (TTX), 5 X 10(-7) M. 3. Perfusion with TRH, 2.5 micrograms microliters-1, caused 198% and 150% increase in ACh release 60 and 80 min after the beginning of the perfusion in the cortex and hippocampus, respectively. After this initial peak, a 100% increase in ACh release persisted throughout the perfusion. 4. Systemic TRH administration was followed by marked hyperactivity and stereotyped behaviour that showed a time course shorter than that of the increase in ACh release. 5. These findings demonstrate that TRH exerts a strong stimulant action on cortical and hippocampal cholinergic pathways. PMID- 1901748 TI - Replacing the mental hospital. Community provision for a district's chronically psychiatrically disabled in domestic environments? AB - Eighteen long-stay patients from an old county asylum moved into hospital hostels. After 12-24 months, there were significant reductions in overall symptoms, as rated by the CPRS and the Krawiecka scale, as well as in deviant but not general behaviour, rated by the REHAB scale. Six later moved to live in supported accommodation. All relatives and patients who expressed an opinion to an independent assessor were satisfied with their present accommodation or wished to move to more independent living. PMID- 1901749 TI - Lithium: long-term effects on the kidney. A prospective follow-up study ten years after kidney biopsy. AB - Forty-six patients with recurrent affective disorders, who began prophylactic treatment with lithium an average of 20 years previously, were followed up prospectively after a ten-year observation period to assess renal function. Nineteen patients had maintained lithium therapy, and eight patients had died. Tubular function was almost unchanged and patients who had continued lithium had not shown increasing urine volumes, but patients who had received lithium in a single daily dosage at night had a significantly lower urinary output than those on a multiple-dosage schedule. The GFR decreased significantly, but the decline was essentially dependent on increasing age, except in two patients who had developed renal insufficiency. Renal function during chronic lithium treatment is related to age, lithium intoxication episodes, pre-existing renal disease, and treatment schedule rather than to duration of prophylactic lithium therapy. PMID- 1901750 TI - Synaptophysin and chromogranin A immunoreactivities in senile plaques of Alzheimer's disease. AB - Immunolabelling for synaptophysin and chromogranin A, two polypeptides associated with small clear and large dense core synaptic vesicles respectively, has been performed on tissue sections of the temporal cortex in Alzheimer's disease in combination with anti-A4 amyloid labelling. The dystrophic neurites in many senile plaques were observed to be labelled by the anti-synaptophysin or anti chromogranin A antibodies. Some diffuse amyloid deposits, demonstrated by antibodies against synthetic amyloid A4 peptides, were associated with a punctuate increase in synaptophysin or chromogranin A immunoreactivity. The labelling of dystrophic plaque neurites may reflect the accumulation in these processes of synaptic vesicles or material derived from them. We suggest also that the punctuate increase in synaptophysin and chromogranin A immunoreactivities associated with some A4 amyloid deposits may be an early event reflecting neuronal dysfunction. PMID- 1901751 TI - Effects of pentobarbital on respiratory functional dynamics in chronically instrumented guinea pigs. AB - Respiratory effects of sodium pentobarbital (35 mg/kg; IP) were studied in guinea pigs chronically instrumented to permit concurrent recordings of bulbar respiratory-related units (RRUs), diaphragmatic electromyogram (DEMG), and electrocorticogram (ECoG). RRU activities were recorded from either the Botzinger Complex (BOT; expiratory) or Nucleus para-Ambiguus (NpA; inspiratory). Pentobarbital-induced changes in respiratory-related activities were evaluated before, throughout the course of, and during recovery from, anesthesia. The most notable development following pentobarbital was a state of progressive bradypnea which was accompanied by a variety of complex changes in the amplitude and temporal attributes of RRU, DEMG and ECoG activities. As anesthetic effects progressed, the activity profiles of both BOT and NpA units underwent striking transformations from a behavioral and state-dependent wakefulness pattern to an activity profile characterized by i) a significantly augmented RRU cycle duration, burst duration and spike frequency; and, ii) an alteration to the pattern of within-burst spike frequency modulation. Along with changes in RRU activity, pentobarbital also produced a marked attenuation of the amplitudes of diaphragmatic activity as well as a discrete, time-dependent alteration in the amplitude and spectral characters of ECoG activities. Differences in BOT and NpA unit responses to alveolar CO2 loading (ramp; 2% and 5%) across wakefulness and anesthesia states were also considerable. In addition to a depressed responsiveness to CO2, the temporal attributes of BOT and NpA activity profiles also indicated an asymmetrical change under pentobarbital anesthesia. Taken together, these findings indicate that pentobarbital causes not only a fundamental alteration in bulbar rhythmogenic mechanisms, but also a differential influence on bulbar respiratory system components that are involved in the definition of the shape and the amplitude of central respiratory drive. In conclusion, this study offers, for the first time, direct evidence from physiologically and structurally intact preparations that the functional dynamics of respiratory system components are profoundly altered during pentobarbital anesthesia. PMID- 1901752 TI - Immunocytochemistry of thyrotropin-releasing hormone in the rabbit medulla oblongata. AB - The distribution and ultrastructure of thyrotropin-releasing hormone-like immunoreactive (TRH-LI) neurons were examined in rabbit medulla oblongata. TRH-LI cell bodies were located in the ventral region of the medulla oblongata: in the paraolivary and parapyramidal regions, regions in and around the pyramidal tract, the dorsolateral region of the lateral reticular nucleus, and the raphe nuclei. The paraolivary and parapyramidal regions contained most of the TRH-LI cell bodies in the medulla oblongata. TRH-LI neurons processes were densely distributed in the dorsal vagal complex and the area postrema. Electron microscopic immunocytochemical studies revealed TRH-LI neurons at the obex level in the paraolivary region of rabbits. TRH-like immunoreactivity was localized in larger granular vesicles. TRH-LI somata and dendrites received synaptic inputs from both TRH-LI and unlabeled axon terminals. More than half of the TRH-LI axon terminals made synapses with somata or processes of TRH-LI neurons. These observations, together with previous reports that TRH causes respiratory facilitation, suggest that TRH-LI neurons in the paraolivary region in rabbits may be involved in respiratory functions. PMID- 1901753 TI - [Comparative study of lysosomal and cytosolic catabolisms of oligomannosidic-type glycans]. AB - In order to study the substrate specificities of the enzymes implicated in the catabolism of oligomannosidic-type glycans, the oligosaccharides Man9GlcNAc and Man5GlcNAc were incubated with rat liver lysosomal and cytosolic alpha-D mannosidases and the hydrolysis products were characterized by 400 MHz 1H-NMR spectroscopy. Although they both occur in an ordered way, the two catabolic pathways are quite different. The lysomal pathway is realized in two stages: the first leads from Man9GlcNAc to Man5GlcNAc by preferential cleavage of the four alpha-1,2-linked mannose residues, and the second, Zn(2+)-dependent, leads from Man5GlcNAc to Man (beta 1-4) GlcN Ac by hydrolysis of alpha-1, 3- and alpha-1,6 linked residues. On the contrary, the cytosolic pattern leads by a pathway quite different to a unique hexasaccharide Man5GlcNAc which has, curiously, the same structure as one of the polyprenolic intermediates occurring in the cytosol during the biosynthesis of N-glycosylprotein glycans: Man (alpha 1-2) Man (alpha 1-2) Man (alpha 1-3) [Man (alpha 1-6)] Man (beta 1-4) GlcN Ac (beta 1-4) GlcNAc alpha 1-P-P-Dol. PMID- 1901754 TI - A gene for limb-girdle muscular dystrophy maps to chromosome 15 by linkage. AB - Limb-girdle muscular dystrophy (LGMD) is inherited as a monogenic, autosomal recessive trait. A genetically homogeneous group of families from the Isle of La Reunion, comprising individuals at high risk for this disorder, was systematically analysed using a panel of 85 polymorphic markers spanning approximately 30% of the human genome. Linkage was detected between the LGMD gene and the marker D15S25, uncovered with the probe pTHH114 and restriction enzyme RsaI (lod score = 5.52 at a 0 = 0.0), localising this gene onto chromosome 15. Such a lod score corresponds to odds of 3.3 x 105 in favor of linkage versus absence of linkage. Additional families from other populations will need to be examined before the role of this newly identified locus can be understood. PMID- 1901755 TI - [Effects of bromadiolone on some organs and tissues (liver, kidney, spleen, blood) of coypu (Myocastor coypus)]. AB - Bromadiolone damaged the erythrocytes, resulting in a probable saturation of transferrin, a deposit of iron in the connective tissue and in a few cells of the proximal tubules of the kidneys and an increased storage of ferritin in the spleen. In the hepatocytes, mitochondria were distorted, their lipid inclusions being granular; a large depletion of glycogen may be considered a reflection of an elevated phosphorylase a ascribable to the proliferation of the smooth endoplasmic reticulum. In the kidneys, pyelonephritis may be irrelevant to the poisoning of the animals. Bromine could not be detected using microanalytical methods. PMID- 1901756 TI - Antierythrocyte autoantibody formation after therapy with interleukin-2 and gamma interferon. AB - The cardiovascular, renal, pulmonary, and dermatologic toxicities of interleukin 2 (IL-2) and gamma-interferon (IFN) are well described. However, autoimmune toxicities have only recently been noticed. The authors report the development of warm autoantibodies against erythrocytes in a patient receiving IL-2 (3.75 x 10(6) cetus units/m2 intravenous bolus three times per week) and gamma-IFN (0.1 mg/m2 subcutaneously three times per week) for metastatic renal cell carcinoma. Other potential causes of autoantibody formation, such as drugs, infection, and collagen vascular disease, were excluded. Both gamma-IFN and IL-2 have the potential to trigger or exacerbate autoimmunity due to either aberrant expression of restricted antigens or inhibition of normal cellular immune suppressor mechanisms. PMID- 1901757 TI - Measuring the cost-effectiveness of hematopoietic growth factor therapy. AB - The increasing cost of and demand for health care have intensified the concern that some form of health care rationing is inevitable. Cost studies require the identification, measurement, and comparison of all significant positive and negative consequences of alternative interventions and may evaluate benefit value, effectiveness, and effect on quality or quantity of life. The hematopoietic growth factors (HGF) will have far-reaching effect on the practice of medicine and, therefore, the design of cost-effectiveness studies are critically important in assessing economic effect. PMID- 1901758 TI - The roles of gamma-interferon and tumor necrosis factor alpha in an experimental rat model of cancer cachexia. AB - Administration of repetitive sublethal doses of either recombinant human tumor necrosis factor (TNF) or recombinant murine gamma-interferon (IFN) to non-tumor bearing (NTB) rats caused a significant decline in food intake and body weight. After 3 days rats became resistant to the anorectic and weight loss effects of TNF but maintained persistent diminished food intake and diminished body weight gain while receiving recombinant murine IFN. Passive immunization against recombinant rat gamma-interferon allowed cachectic tumor-bearing (TB) rats to eat more food, have a lesser decline in body weight, live longer, and tolerate larger tumors than similar TB rats given nonspecific control antibody. TB rats treated with an antisera to recombinant murine TNF, which was 100% protective when given to NTB rats 6 h before a lethal endotoxin challenge, did not differ significantly from TB rats treated with control antibody with respect to food intake, body weight, survival, or tumor size. Serum levels of TNF or IFN were not detectable in cachectic tumor-bearing rats. The data indicate that the administration of exogenous IFN can simulate cachexia in NTB rats and that passive immunization against it can partially reverse the cachectic changes associated with cancer and prolong survival. These findings suggest that gamma-interferon may be an important mediator of cachexia in this rat tumor model. PMID- 1901759 TI - Synergistic antitumor effects of rat gamma-interferon and human tumor necrosis factor alpha against androgen-dependent and -independent rat prostatic tumors. AB - We have examined the antitumor effects of rat gamma-interferon (IFN-gamma) and human tumor necrosis factor alpha (TNF) against androgen-dependent and independent Dunning rat prostatic tumors. In vitro studies, using the double layer soft agar assay, showed a very limited antiproliferative activity of the drugs in the dose range tested (1-1000 units IFN-gamma and/or 1-1000 ng TNF/dish). For in vivo studies IFN-gamma and TNF were administered s.c., peritumorally. IFN-gamma was given 3 times/week, 8,000 or 80,000 units/rat, and TNF 5 times/week, 10 or 100 micrograms/rat. IFN-gamma and TNF monotherapy were not significantly effective in inhibiting tumor growth, except for IFN-gamma against the androgen-independent MatLyLu tumor. Combinations of IFN-gamma and TNF had synergistic antiproliferative effects against all four tumor lines tested; however, complete growth inhibitions could not be achieved. Survival studies showed significant increase in survival of tumor-bearing rats. PMID- 1901761 TI - Promotion of aflatoxin B1 carcinogenesis by the natural tumor modulator indole-3 carbinol: influence of dose, duration, and intermittent exposure on indole-3 carbinol promotional potency. AB - Indole-3-carbinol (13C), a secondary metabolite from cruciferous vegetables, inhibits aflatoxin B1 (AFB1) hepatocarcinogenesis in trout (Bailey et al., J. Natl. Cancer Inst., 78: 931-934, 1987) and rats (Selivonchick et al., unpublished results) when given prior to and with carcinogen but promotes carcinogenesis in both species when given continuously following AFB1 initiation. Since human 13C intake may not be continuous, and the promotional stimulation may be reversible, we have assessed 13C promotion using delayed and discontinuous exposure protocols. Following initiation with AFB1, 13C was fed to trout for varying periods of time, with varying lengths of delay after initiation and continuous or intermittent patterns of 13C treatment. Promotional enhancement of tumor incidence by 13C was found to be significant when 13C treatment was delayed for several weeks or months after the initial AFB1 challenge. Promotion also was found to increase with length of exposure to 13C treatment and to be decreased but still evident when 13C was given in alternating months or weeks, or twice per week only. These results do not support the idea that promotional stimulation in hepatocarcinogenesis is a reversible phenomenon. To quantify 13C promotional potency in terms of its dietary concentration, a series of AFB1 tumor dose response curves was established, each with a different level of 13C fed continuously following AFB1 initiation. The resultant tumor dose-response curves, plotted as logit percentage of incidence versus log AFB1 dose, were displaced parallel toward lower AFB1 50% tumor take (TD50) values with increasing 13C concentration. The level of 13C that halves the AFB1 dose for 50% tumor incidence was calculated to be approximately 1000 ppm 13C, fed continuously, with no substantial threshold for promotion. By comparison, 13, when fed before and with AFB1, shows a 50% inhibitory value (13C concentration that doubles the dose of AFB1 for 50% tumor incidence) in trout of 1400 ppm 13C [Dashwood et al., Carcinogenesis (Lond.), 10: 175-181, 1989]. Thus the potential for 13C as a dietary additive to promote prior hepatic initiation events when fed continuously is approximately as great as its potential to inhibit concurrent AFB1 initiation. PMID- 1901760 TI - Interferon enhancement of radioimmunotherapy for colon carcinoma. AB - Recombinant human gamma-interferon (IFN-gamma) has recently been shown to enhance localization of radiolabeled monoclonal antibodies (MAb) to human colon carcinoma xenografts in athymic mice. The present study investigates the ability of gamma interferon to enhance radioimmunotherapy of a low carcinoembryonic antigen expressing human colon cancer (WiDr) in athymic mice. Growth curve analysis, antibody localization, and dose estimation studies were performed. A significant tumor growth delay, measured as the time to reach 1.0 g, was noted for animals receiving specific anti-carcinoembryonic antigen 90Y-MAb (ZCE025, 120 microCi) plus IFN-gamma (61.8 days) as compared to animals that received specific 90Y-MAb with phosphate-buffered saline (34.9 days; P less than 0.005). IFN-gamma (100,000 units) was given i.p. every 8 h for 2 days before and 4 days after 90Y-MAb therapy. The time required to reach 1.0 g for animals treated with nonspecific 90Y-MAb (ZME018) was significantly less either with (38.3 days) or without (34.4 days) IFN-gamma. The difference was more apparent when compared to animals receiving IFN-gamma alone (30.0 days) or phosphate-buffered saline alone (28.9 days; P less than 0.001). Increased antibody localization in the tumors of animals treated with IFN-gamma plus specific 90Y-MAb (43.2% injected dose/g) was seen in comparison to animals treated with specific 90Y-MAb without IFN-gamma (18.2% injected dose/g). The estimate of radiation dose delivered to the tumors, based on biodistribution data over time, revealed significantly higher levels in animals treated with specific 90Y-MAb with IFN-gamma (2477 cGy) compared to animals treated without IFN-gamma (1217 cGy). These results provide support for the use of gamma-interferon as an immunomodulating agent prior to radioimmunotherapy. PMID- 1901762 TI - Prophylactic therapy of cluster headaches. PMID- 1901763 TI - Effect of low temperature on the cytosolic free Ca2+ in rat ventricular myocytes. AB - The effect of low temperature on the cytosolic free Ca2+ [( Ca2+]i) has been investigated in isolated ventricular myocytes from adult rats using the fluorescent probe Indo-1. The distribution of Indo-1 between the mitochondrial and cytoplasmic compartments was first determined in the isolated myocytes using the digitonin and Triton X-100 treatments. By subtracting the mitochondrial [Ca2+]i from the total [Ca2+]i measured with Indo-1, the average cytosolic [Ca2+]i was found to increase significantly (P less than 0.05) from 139 nM to 255 and 297 nM when the temperature was decreased from 37 degrees C to 15 degrees and 5 degrees C, respectively. A marked increase in cytosolic [Ca2+]i to a new steady state level was observed when the membrane of myocytes was depolarized by 60 mM KCI; the average magnitude of increase being 110, 243 and 186 nM, at 37 degrees, 15 degrees and 5 degrees C respectively. Our results support the hypothesis that the cardiac arrhythmia typically observed in the hypothermic rat is due to an increased cytosolic [Ca2+]i with decreasing body temperature. PMID- 1901764 TI - Ablation of "tolerance" and induction of diabetes by virus infection in viral antigen transgenic mice. AB - To address the mechanisms of tolerance to extrathymic proteins, we have generated transgenic mice expressing the lymphocytic choriomeningitis viral (LCMV) glycoprotein (GP) in the beta islet cells of the pancreas. The fate of LCMV GP specific T cells was followed by breeding the GP transgenic mice with T cell receptor transgenic mice, specific for LCMV and H-2Db. These studies suggest that "peripheral tolerance" of self-reactive T cells does not involve clonal deletion, clonal anergy, or a decrease in the density of T cell receptors or accessory molecules. Instead, this model indicates that self-reactive cytotoxic T cells may remain functionally unresponsive, owing to a lack of appropriate T cell activation. Infection of transgenic mice with LCMV readily abolishes peripheral unresponsiveness to the self LCMV GP antigen, resulting in a CD8+ T cell-mediated diabetes. These data suggest that similar mechanisms may operate in several so called "T cell-mediated autoimmune diseases." PMID- 1901765 TI - Virus infection triggers insulin-dependent diabetes mellitus in a transgenic model: role of anti-self (virus) immune response. AB - We investigated the potential association between viruses and insulin-dependent (type 1) diabetes (IDDM) by developing a transgenic mouse model. By inserting into these mice a unique viral protein that was then expressed as a self-antigen in the pancreatic islets of Langerhans, we could study the effect on that expressed antigen alone, or in concert with an induced antiviral (i.e., autoimmune) response manifested later in life in causing IDDM. Our results indicate that a viral gene introduced as early as an animal's egg stage, incorporated into the germline, and expressed in islet cells does not produce tolerance when the host is exposed to the same virus later in life. We observed that the induced anti-self (viral) CTL response leads to selective and progressive damage of beta cells, resulting in IDDM. PMID- 1901766 TI - Effect of recombinant interleukin 5 on the generation of cytotoxic T cells (CTL). AB - The effect of recombinant human interleukin 5 (rhIL5) on the generation of CTL was investigated by using autologous EBV-transformed B cells as the target. Exogenous IL5 augmented the CTL generation, and its effect was most active at the concentration of 10 ng/ml, and when added at the late phase of culture in this system. IL5 augmented specific CTL activity rather than MHC nonrestricted CTL activity as detected with K562 and Daudi when compared to that augmented by IL2. IL5 did not increase the expression of p55 or p75 IL2R nor the responsiveness to IL2. Taken together with the finding that IL5 augmented the CTL activity even in the presence of cyclosporin A, the effect of IL5 on the CTL generation seems not to act through the IL2-IL2R system. PMID- 1901767 TI - IL-4-supported induction of cytolytic T lymphocytes requires IL-2 and IL-6. AB - Previous work indicated that a CTL response can be generated by the combination of IL-2 plus IL-6 or IL-4 alone. Because of the ubiquitous production of IL-6 and its apparent ability to induce IL-2, we explored the interdependence of these lymphokines in supporting a CTL response from murine thymocytes. For thymocytes cultured in IL-4, further addition of IL-6 enhanced thymocyte proliferation. In addition, a role for IL-6 in thymocyte activation was indicated by the ability of anti-IL-6 mAb to block both IL-4-directed proliferation and the cytotoxic response found in the presence of IL-4. The addition of IL-2 to limiting doses of IL-4 augmented the CTL response; however, the response to high levels of IL-4 was not augmented by addition of IL-2. Consistent with this apparent involvement of IL-2 in the IL-4-mediated response we found: (a) that mAb to IL-2 significantly reduced the CTL response generated in the presence of IL-4; (b) that IL-2 activity was present in culture supernatant following incubation of thymocytes with high levels of IL-4; and (c) that enhanced IL-2 receptor expression found in the presence of IL-4 was blocked with the addition of anti-IL-2 antibody to the thymocyte culture. In contrast to the data for proliferation, anti-IL-4 mAb had no effect on the generation of CTL in the presence of IL-2 + IL-6 but readily blocked the CTL response to IL-4. These results indicate that, for thymocyte responders, the CD8+ CTL generated in the presence of IL-4 require both IL-2 and IL-6. PMID- 1901768 TI - Constitutive antigen presentation by mouse splenic macrophages is restricted to the progeny of a distinct progenitor population. AB - Mouse splenic macrophage progenitors differ in their ability to give rise to cloned progeny that constitutively present complex protein antigens to T-cell hybridomas. To determine if the constitutive presentation of diverse antigens is restricted to cells derived from the same subpopulation of progenitors, we expanded macrophage clones into multiple subcultures and compared them for the ability to present different antigens to their respective antigen-specific T-cell hybridomas. Only subcultures derived from the same minority fraction of splenic macrophage progenitors were capable of constitutively presenting the antigens, and the activity of these subcultures was unaffected by the addition of recombinant murine IFN-gamma. This suggests that a specialized sub-population of constitutive antigen-presenting macrophages exists in the spleens of mice. PMID- 1901769 TI - Activation of murine T cells by staphylococcal enterotoxin E: requirement of MHC class II molecules expressed on accessory cells and identification of V beta sequence of T cell receptors in T cells reactive to the toxin. AB - We investigated a mechanism leading to activation of murine T cells by staphylococcal enterotoxin E (SEE). L cells transfected with I-Ab genes but not control L cells supported IL-2 production by SEE-induced C57BL/6 T lymphoblasts upon restimulation with SEE. mAb to I-Ab markedly inhibited the above response. Flow cytometric analyses showed that SEE-induced C57BL/6 T lymphoblasts are composed of both CD4+ T cells and CD8+ T cells, and that larger parts of them bore V beta 11 (40-75%). mAb to V beta 11 markedly inhibited the SEE-induced proliferative response and IL-2 production by T cells. Analysis of SEE-induced IL 2 production in spleen cells from various mouse strains showed that C57BL/6 and B10.A(4R) mice (I-E, not expressed; V beta 11+ T cells, normally generated) are highly responsive to SEE. In contrast, BALB/c, C3H/HeN, (C57BL/6 x BALB/c or C3H/HeN) F1 mice (I-E, normally expressed and V beta 11+ T cells, deleted), and SJL and C57L mice (V beta 11 genes, deleted) are weakly responsive to SEE. The results indicate that SEE activates mainly T cells bearing V beta 11 in physical association with MHC class II molecules expressed on AC. In addition, the results indicate that SEE activates both CD4+ T cells and CD8+ T cells. PMID- 1901771 TI - Can serum ferritin be effectively interpreted in the presence of the acute-phase response? PMID- 1901770 TI - Induction of unresponsiveness to Heymann's nephritis: inhibited by monoclonal antibody to CD4 but not to CD8. AB - The effects of mAb therapy to CD4 or CD8 on induction of unresponsiveness to Heymann's nephritis by preimmunization with renal tubular antigen in IFA. Anti CD4 mAbs (MRC Ox35) given for 2 weeks after RTA/IFA completely prevented the induction of resistance to HN, all rats developing proteinuria as well as high titers of autoantibody and Ig and C deposits in glomeruli. Anti-CD8 mAbs (MRC Ox8) did not prevent induction of unresponsiveness, even though it totally depleted CD8+ cells. In control rats not preimmunized with RTA/IFA, mAb therapy did not suppress disease induction, but in the case of anti-CD4 therapy enhanced the severity of disease. Persistent depletion of T cell subsets or complement components did not explain the effects of mAb therapy. These studies suggest that CD4+ cells are critical for the induction of unresponsiveness to HN and that therapy with mAb to CD4 can prevent induction of tolerance to an antigen, which has implications for its use in the induction of tolerance. PMID- 1901772 TI - Urinary excretion of glycated protein determined with a specific radioimmunoassay. AB - We developed a simple and highly sensitive RIA for glycated protein (GP), and used it to measure GP in serum and urine from 15 normal controls and 30 diabetics (14 with urinary excretion rate of albumin, Ualb less than 15 micrograms/min, group A; nine with 15 less than or equal to Ualb less than or equal to 150 micrograms/min, group B; and seven with Ualb greater than 150 micrograms/min, group C). The mean serum concentration of GP was above normal in all groups of diabetics, and the mean glycation ratios of serum protein (SGP) were higher in groups B and C than in normal subjects. Urinary concentrations of GP also were increased in groups B and C, although the glycation ratio of urinary protein (UGP) was decreased in group C. Consequently, the selectivity of urinary excretion of GP (UGP/SGP) was significantly decreased in group C. Moreover, there was a significant difference in the mean values of selectivity between groups of patients with various degrees of retinopathy. We suggest that measurements of serum and urinary GP are useful to evaluate the progression of diabetic complications. PMID- 1901773 TI - Development of a radioligand receptor assay for measuring follitropin in serum: application to premature ovarian failure. AB - We have developed a radioligand receptor assay (RRA) with sufficient sensitivity and specificity for quantifying follitropin (FSH) in unextracted serum samples. Standard curves prepared by adding pituitary FSH to either buffer or gonadotropin free serum were parallel and statistically indistinguishable in this assay, whereas gonadotropin-free serum alone had no activity. Cross-reactivity with related pituitary hormones was negligible. Pituitary FSH was calibrated with commonly used reference preparations so that RRA results could be compared with RIA results for identical standards. The patterns in daily blood samples in six normal menstrual cycles were similar by both methods. The mean RIA:RIA ratio in both the follicular and luteal phases was between 0.6 and 0.7, and at mid-cycle decreased to 0.48, suggesting an alteration of isohormone composition at mid cycle. In 27 women with premature ovarian failure, RRA:RIA ratios ranged from below the RRA minimum detectable dose to 4.6, suggesting that immunoreactive FSH might not be capable of binding to the FSH receptor in some patients, whereas in patients with high RRA:RIA ratios, circulating inhibitors of FSH receptor binding might be present and perhaps contributing to the observed ovarian failure. Use of this RRA in conjunction with RIA and in vitro bioassays may better define the relative contribution of FSH isohormones, autocrine or paracrine modulators of FSH bioactivity, and FSH-receptor binding competitors to the "total FSH biological signal" as detected by the gonadal FSH receptor. PMID- 1901774 TI - Comparison of four methods for free thyroxin. AB - We performed a limited evaluation of four free thyroxin (FT4) reagent kits: the Amerlex-M (AFT4), the Amerlite (LFT4), the MagicLite (MFT4), and the GammaCoat two-step RIA (GFT4). FT4 was measured in specimens from 201 subjects: 19 healthy controls, 14 patients who were thyrotoxic, 13 who were hypothyroid, 59 who had a past history of thyroid disease, seven with thyroxin autoantibodies, seven who were taking amiodarone, and 82 who had no clinical indication of thyroid hormone abnormality. Of these 201 subjects, 78 had a low serum albumin (less than 35 g/L) and 27 had severe nonthyroidal illness. We also investigated 60 pregnant subjects. We found no correlation between thyroxin-binding globulin (TBG) and FT4 in any of the assays, and only the AFT4 method showed a significant correlation with albumin concentrations. The presence of autoantibodies to thyroxin affected the results of all methods except the GFT4 method. All methods showed a decrease in mean FT4 values in late pregnancy. Correlation of patients' clinical state and FT4 results suggested that the reference ranges published by the manufacturers need to be modified for our laboratory. PMID- 1901775 TI - The spot test is not a reliable screening procedure for mucopolysaccharidoses. AB - To check the reliability of the Ames MPS paper spot test, which is based on the Azure A dye, we sent a series of urine samples to three laboratories where the spot test is part of the metabolic screening for mucopolysaccharidoses. In these laboratories false-negative results ranged between 19% and 35% and false-positive results ranged between 12% and 29% of all samples submitted. In contrast, the quantitative dimethylmethylene blue test (Clin Chem 1989;35:1472-7) detected an increased glycosaminoglycan content in all urine samples from mucopolysaccharidosis patients and gave no false-positive results. In the latter procedure, glycosaminoglycan content is expressed per millimole of creatinine, and age-dependent reference values are used. We conclude that the Ames spot test and other spot tests are unreliable as a screening procedure for mucopolysaccharidoses and should not be used to screen for these diseases. PMID- 1901776 TI - Altered production of tumour necrosis factors alpha and beta and interferon gamma by HIV-infected individuals. AB - In vitro studies shows that recombinant tumour necrosis factor (TNF) alpha and beta, and interferon-gamma (IFN-gamma) can enhance HIV replication, and peripheral blood mononuclear cells (PBMC) infected with HIV in vitro secrete high levels of the same cytokines. As T cells secrete all three mediators, the capacity of T cell activation signals to trigger cytokine production in PBMC from HIV-infected individuals was investigated as such patients may be immunocompromised. We demonstrate that asymptomatic seropositives in CDC group II/III as well as patients who have progressed to CDC group IV of the disease proliferate efficiently to anti-CD3 antibody, recombinant interleukin-2 (rIL-2), phytohaemagglutinin (PHA), PHA plus phorbol 12,13 dibutyrate (PMA) but secrete significantly (P less than 0.05) higher amounts of TNF-alpha, TNF-beta and IFN gamma compared with controls in response to the same stimulants. We also show a difference between group II/III and group IV patients with the latter secreting more TNF-alpha and IFN-gamma. The kinetics of TNF-alpha and -beta, and IFN-gamma production was stimulus dependent with overall levels varying in time for each stimulus. Furthermore, the kinetics of the response to all three stimulants were altered in seropositives; CDC group II/III and group IV patients secreted higher levels of cytokines over several time points compared to controls. The altered production of these mediators by HIV-infected patients may contribute to disease progression and to the pathogenesis of AIDS. PMID- 1901777 TI - Genetic studies on experimental autoimmune gastritis induced by neonatal thymectomy using recombinant inbred strains between a high-incidence strain, BALB/c, and a low-incidence strain, DBA/2. AB - Thymectomy on day 3 after birth induced autoimmune gastritis (AIG) at the age of 2 months in 51-73% of BALB/c mice, and in only 3-5% of DBA/2 mice. AIG was detected by histological and serological (immunofluorescence staining for detecting anti-parietal cell autoantibody) examination. However, autoantibody was weakly positive in almost all of these DBA/2 mice when measured by ELISA using extract of murine gastric mucosa as the antigen. To investigate genetically the mechanism controlling the incidence of AIG, II recombinant inbred strains established by brother-sister mating of (BALB/c x DBA/2) F2 mice (C x D2 strains) were used. Among 26 markers tested, the Mls-1 locus on BALB/c chromosome 1 and the Hc locus coding a complement component (C5) on BALB/c chromosome 2 were found to be associated with high susceptibility to AIG. However, if one or both of the loci were of DBA/2 origin, mice showed medium or low susceptibility to AIG. For further analysis, F1, F2 and back-cross generations of these two strains were tested, but segregation of a single susceptibility or insusceptibility gene was not obtained. Taken together, it seems probable that two or more genes are involved in the induction mechanism of AIG. We did not detect C5 deposition in AIG lesions, nor complement-dependent cytotoxic antibody to parietal cells in serum from AIG mice. However, injection of irradiated spleen cells of DBA/2 mice into BALB/c mice thymectomized on day 3 augmented the incidence of AIG from 71 to 100%, but not that of oophoritis (33%). A relationship between Mls-1a determinants and the pathogenesis of AIG was further suggested from the fact that V beta 6 TcR-expressing T cells increased in number in AIG-bearing compared with normal BALB/c mice. PMID- 1901778 TI - Expression of MHC class I and II molecules by cadaver retinal pigment epithelium cells: optimization of post-mortem HLA typing. AB - The objective of this study was to investigate the expression of MHC antigens by retinal pigment epithelium cells (RPE) after stimulation with interferon-gamma (IFN-gamma) and to improve the currently practised technique of cadaver HLA typing. A concentration of 100 U/ml IFN-gamma induced expression of class I molecules up to greater than 90% 3 days after stimulation, whereas 50 U/ml were required for the expression of HLA-DR to greater than 90%. A concentration of 750 U/ml induced 35-45% expression of HLA-DP and less than 25% HLA-DQ after 3 days. Cells were serologically typed using the standard lymphocytotoxicity assay 3 days after stimulation with 250 U/ml IFN-gamma. Typing of class I specificities was complemented by one-dimensional isoelectric focusing (1D-IEF). We observed high concordance between the results of the RPE typing and the lymphocytotoxicity test on the same donors. Our results show complete typing of class I and II antigens post-mortem, which, in particular, enables graft matching and improvement of graft survival in recipients of organs removed many hours after death such as the cornea. PMID- 1901779 TI - Selective deficiency of interferon-gamma production in the hyper-IgE syndrome. Relationship to in vitro IgE synthesis. AB - We measured the in vitro production of interferon-gamma (IFN-gamma) in five cases of hyper-IgE syndrome (HIgE), induced by mitogens, calcium ionophores and phorbol ester. The biosynthesis of IFN-gamma was severely reduced or undetectable in HIgE, while it was near normal in most atopic patients. The in vitro spontaneous production of IgE was increased overall in HIgE patients, although no correlation was found with serum IgE levels. Recombinant interleukin-4 (IL-4) induced a further increase in IgE synthesis, and its effect was totally antagonized by recombinant IFN-gamma; the same pattern of response was also observed in atopic subjects with high production of IgE. IFN-alpha synergized with IL-4 on IgE synthesis, whereas recombinant IL-6 gave opposite changes in individual cases tested. We propose that IFN-gamma deficiency may be responsible for some of the features of HIgE patients, including IgE levels and infections. PMID- 1901782 TI - Differing effects of the anxiolytic agents buspirone and diazepam on control of breathing. AB - We compared ventilatory effects of the nonsedating anxiolytic buspirone with those of the sedating anxiolytic diazepam in nine normal men. Resting ventilatory parameters and ventilatory responses to CO2 rebreathing and inspiratory threshold loading were measured before and after placebo, diazepam, and buspirone. Placebo had no ventilatory effects. Diazepam had no effect on resting ventilation but depressed response to CO2. Buspirone had no effect on resting ventilation or CO2 response. During loading, buspirone did not alter the augmentation of mouth pressure; diazepam produced a trend toward less augmentation. Both anxiolytics altered the load compensation response for the group; in particular, an increase in ventilation during loading (seen in three of nine subjects) was suppressed by drug administration. Diazepam also markedly depressed one subject's loaded ventilation below unloaded ventilation. In summary, buspirone did not cause the depression of respiratory center chemosensitivity that was seen with diazepam and produced less depression of load compensation in normal subjects. This suggests that it may be a safer anxiolytic in patients with lung disease. PMID- 1901780 TI - Antibody penetration of viable human cells. I. Increased penetration of human lymphocytes by anti-RNP IgG. AB - Antibody penetration of viable cells and interaction with intracellular antigens may have major consequences for immunopathological processes in connective tissue diseases. We have reported previously that antibody can penetrate viable human lymphocytes. To assess further the role of antinuclear antibodies in this process, peripheral blood lymphocytes (PBMC) were incubated with FITC-conjugated IgG fractions from sera containing anti-RNP (anti-RNP IgG), Ro(SS-A), La(SS-B) and dsDNA antibodies and control sera for 24 h. Using crystal violet to quench cell surface staining, intracellular fluorescence of viable lymphocytes was quantified on the flow cytometer. It was noted that anti-RNP IgG entered 46.4 +/- 7.2% of lymphocytes which was significantly higher than anti-Ro(SS-A) (29.9 +/- 4.1%, P less than 0.05), La(SS-B) (22.0 +/- 7.5%, P less than 0.01) IgG and control IgG (28.8 +/- 2.1%, P less than 0.05) and not statistically different from anti-dsDNA IgG (32.6 +/- 14.3%). Inhibition experiments showed that the increased number of cells penetrated by anti-RNP IgG was a specific process. Time course studies showed that anti-RNP IgG entry into cells was different from pooled control IgG. With anti-RNP IgG, positive-staining lymphocytes gradually increased in number from 12 to 24 h incubation, whilst with pooled control IgG, the peak was reached within 5 min. Dual staining experiments suggested that whereas both anti-RNP IgG and pooled control IgG entered B and NK cells, anti-RNP IgG also entered T cells. Using IgG F(ab')2 and Fc fragments from either anti-RNP IgG or pooled control IgG to compete with their FITC-conjugated counterparts indicated that the entry of anti-RNP IgG into-viable cells appeared to involve both F(ab')2 and Fc fragments, and pooled control IgG depended exclusively on the Fc portion of IgG. Further investigation by incubating anti-RNP IgG with 35S methionine-labelled monocyte-depleted PBMC (MD-PBMC) suggested that anti-RNP IgG might react with the corresponding antigens either on the cell surface or within the cytoplasm. PMID- 1901781 TI - Effect of catechins and citrus flavonoids on invasion in vitro. AB - Catechins, a group of flavonoid molecules, inhibit invasion of mouse MO4 cells into embryonic chick heart fragments in vitro. The anti-invasive effects can be ranked as follows: (+)-catechin greater than (-)-epicatechin greater than 3-O methyl-(+)-catechin greater than 3-O-palmitoyl-(+)-catechin. Most of the catechins are unstable in cell culture media, and their spontaneous rearrangement products tend to bind to extracellular matrix (ECM). Due to these interactions proteases such as tissue-type plasminogen activator (t-PA) are linked to the ECM glycoprotein laminin. This leads to a partial inactivation of the enzyme. Within the group of catechins we found a positive correlation between anti-invasive activity and linking of t-PA to laminin. Citrus flavonoids are also anti-invasive in vitro (tangeretin greater than nobiletin greater than hesperidin = naringin). However, these stable molecules show poor affinity for ECM, and do not link enzymes to laminin. These data suggest that catechins and citrus flavonoids inhibit invasion in vitro by different mechanisms. PMID- 1901783 TI - Subfreezing volumetric behavior and stochastic modeling of intracellular ice formation in Drosophila melanogaster embryos. AB - Cryomicroscopic observations were made of the volumetric behavior and kinetics of intracellular ice formation (IIF) in Drosophila melanogaster embryos in a modified cell culture medium (BD.20) or BD.20 + 2 M ethylene glycol. After rapid cooling to a given temperature, transient volumetric contraction of the embryos during the isothermal period was quantified by computerized video image analysis. Fitting these data to the numerical solution of the volume flux equation yielded estimates of the hydraulic permeability coefficient (Lp) for individual embryos at various subfreezing temperatures. Lp approximately followed an Arrhenius relation between -2 and -9 degrees C, with a value of 0.168 microns/(min-atm) extrapolated to 0 degrees C and an apparent activation energy delta E of 38.9 kcal/mol. IIF during an isothermal period occurred at random times whose characteristic temperature range and kinetics were affected by the presence of ethylene glycol. A stochastic process model developed to fit these data indicated the influence of both time-dependent and instantaneous components of IIF, presumed to be the result of seeding and heterogeneous nucleation, respectively. The presence of 2 M ethylene glycol depressed the characteristic temperature of instantaneous IIF by about 12 degrees C and reduced the rate constant for time dependent IIF. Comparison with observed incidences of IIF yielded an estimate of the supercooling tolerance of 3 to 5 degrees C. PMID- 1901784 TI - Dynamic changes in the distribution of cytoplasmic myosin during Drosophila embryogenesis. AB - Dramatic changes in the localization of conventional non-muscle myosin characterize early embryogenesis in Drosophila melanogaster. During cellularization, myosin is concentrated around the furrow canals that form the leading margin of the plasma membrane as it plunges inward to package each somatic nucleus into a columnar epithelial cell. During gastrulation, there is specific anti-myosin staining at the apical ends of those cells that change shape in regions of invagination. Both of these localizations appear to result from a redistribution of a cortical store of maternal myosin. In the preblastoderm embryo, myosin is localized to the egg cortex, sub-cortical arrays of inclusions, and, diffusely, the yolk-free periplasm. At the syncytial blastoderm stage, myosin is found within cytoskeletal caps associated with the somatic nuclei at the embryonic surface. Following the final syncytial division, these myosin caps give rise to the myosin rings observed during cellularization. These distributions are observed with both whole immune serum and affinity-purified antibodies directed against Drosophila non-muscle myosin heavy chain. They are not detected in embryos stained with anti-Drosophila muscle myosin antiserum or with preimmune serum. Although immunolocalization can only suggest possible function, these myosin localizations and the coincident changes in cell morphology are consistent with a key role for non-muscle myosin in powering cellularization and gastrulation during embryogenesis. PMID- 1901785 TI - Carbonic anhydrase III, an early mesodermal marker, is expressed in embryonic mouse skeletal muscle and notochord. AB - Carbonic anhydrase III (CAIII) is an abundant soluble protein in adult mammalian slow twitch skeletal muscle fibers. It is thought to be an early marker for myogenesis based upon its high level of expression in myoblasts in vitro prior to fusion. Using in situ hybridization, we have studied the in vivo distribution of CAIII gene transcripts in mouse embryos and fetuses from 7.25 days to 17.5 days post coitum (p.c.). CAIII mRNAs are first detected in the myotomes of somites between 9.5 and 10.5 days p.c. (20-30 somites). At 15.5 days p.c., CAIII begins to be restricted to developing slow muscle fibers. By two weeks post partum (p.p.), CAIII mRNAs are detected mainly in slow muscle fibers. CAIII transcripts are detected at an earlier stage (7.25 days p.c.) in the developing notochord. CAIII is expressed at a much higher level in the notochord than it is in developing skeletal muscle. As the notochord forms the nucleus pulposus in fetal mice, CAIII mRNA levels remain very high. Expression of CAIII in the notochord is of interest in the context of skeletal myogenesis because the notochord is thought to play an important role in somite formation. In addition to the notochord, CAIII transcripts are detected prenatally in several other non-muscle tissues: in cells of the choroid plexus, endocardial cushion and ureter, and in adipocytes. PMID- 1901786 TI - The origin of postembryonic neuroblasts in the ventral nerve cord of Drosophila melanogaster. AB - Embryonic and postembryonic neuroblasts in the thoracic ventral nerve cord of Drosophila melanogaster have the same origin. We have traced the development of threefold-labelled single precursor cells from the early gastrula stage to late larval stages. The technique allows in the same individual monitoring of progeny cells at embryonic stages (in vivo) and differentially staining embryonic and postembryonic progeny within the resulting neural clone at late postembryonic stages. The analysis reveals that postembryonic cells always appear together with embryonic cells in one clone. Furthermore, BrdU labelling suggests that the embryonic neuroblast itself rather than one of its progeny resumes proliferation as a postembryonic neuroblast. A second type of clone consists of embryonic progeny only. PMID- 1901787 TI - Glycosaminoglycans in horses with osteoarthritis. AB - Horse articular cartilage glycosaminoglycans (GAGs) were measured in synovial fluids from 48 joints affected with osteoarthritis (OA), 22 normal joints, four joints with osteochondritis, three joints with traumatic arthritis and seven joints infected with bacteria. Serum and urine from individual horses were also examined for the presence of GAGs. High levels of GAGs were found in synovial fluids (SF) from horses with OA. In each case, the level was higher in the synovial fluid than in the serum or urine from the same horse. Horses with OA showed high GAG levels in SF, serum and urine compared to horses with normal and infected joints. High levels were also found in horses with osteochondritis and traumatic arthritis. Levels of synovial fluid GAG reflect cartilage destruction in arthritis and may be useful for monitoring disease progression in the equine species. PMID- 1901788 TI - Prolongation of xylazine/ketamine induced recumbency time with temazepam in horses. AB - Short term anaesthesia induced with xylazine and ketamine was compared to a combination of xylazine, ketamine and temazepam (a benzodiazepine) in six adult horses. Duration of recumbency was significantly prolonged when temazepam was administered with xylazine and ketamine. No significant differences in heart rate, respiratory rate, blood pressure or arterial pH, pCO2 and pO2 were seen between the xylazine and ketamine combination plus temazepam, and xylazine and ketamine combination only treated horses. PMID- 1901789 TI - Kringle-2 domain of the tissue-type plasminogen activator. 1H-NMR assignments and secondary structure. AB - A recombinant 90-residue polypeptide fragment containing the three-loop kringle-2 domain of human tissue-type plasminogen activator (t-PA) has been studied by two dimensional 1H-NMR spectroscopy at 500 MHz. Complete sequence-specific resonance assignments were derived. Overall, the kringle exhibits a compact, folded conformation with more than 50% of the residues in irregular structures. Elements of secondary structure were identified from sequential, medium- and long-range dipolar (Overhauser) interproton interactions. These identifications were corroborated by analysis of spin-spin scalar 3J alpha N splittings and identification of backbone amide NH protons exhibiting retarded 1H/2H exchange in 2H2O. Three antiparallel beta-sheets and six tight turns were located. In addition, one short alpha-helical region was found in the Ser43-Ala44-Gln44a Ala44b-Leu44c-Gly45+ ++ segment; this region contains three-residue insertions unique to the t-PA and urokinase kringles. Although the secondary structure of the t-PA kringle 2 in solution is in overall agreement with that observed in the crystallographic structure of the prothrombin kringle 1 [Tulinsky, A., Park, C.H. & Skrzypczak-Jankun, E. (1988) J. Mol. Biol. 202, 885-901], the alpha-helical segment and other details of the secondary structure differ somewhat from the prothrombin homolog. PMID- 1901790 TI - Studies on RNase T1 mutants affecting enzyme catalysis. AB - Using an Escherichia coli overproducing strain secreting Aspergillus oryzae RNase T1, we have constructed and characterized mutants where amino acid residues in the catalytic center have been substituted. The mutants are His40----Thr, Glu58-- -Asp, Glu58----Gln, His92----Ala and His92----Phe. His92----Ala and His92----Phe mutants are inactive. On the basis of their kcat/Km values, the mutants Glu58--- Asp and Glu58----Gln show 10% and 7% residual activity, relative to wild-type RNase T1, whereas the His40----Thr mutant shows 2% activity. The effect of amino acid substitutions on the enzymatic activity of RNase T1 lends further support for a mechanism where Glu58 (possibly activated by His40 and His92 act as general base and acid respectively; this is discussed in terms of the known three dimensional structure of the enzyme. PMID- 1901792 TI - Self-abatement of simple partial epileptic seizures. AB - Two patients with simple partial epileptic seizures were able to abate their attacks by vigorous somatosensory stimulation of the body part initially involved by the seizure. In both patients, the seizure symptoms progressed in a marching fashion which suggests a gradual spread of the epileptic discharge from its initial locus to adjacent areas. PMID- 1901791 TI - Staphylococcal phosphoenolpyruvate-dependent phosphotransferase system. Purification and protein sequencing of the Staphylococcus carnosus histidine containing protein, and cloning and DNA sequencing of the ptsH gene. AB - The histidine-containing protein (HPr) of the bacterial phosphoenolpyruvate dependent phosphotransferase system (PTS) was isolated from Staphylococcus carnosus and purified to homogeneity. The protein sequence was determined by Edman degradation of peptides obtained by proteolytic digestion with proteases V8, trypsin and chemical cleavage with BrCN. Furthermore, immunological screening of a chromosomal S. carnosus DNA gene library in pUC19 vector enabled us to isolate S. carnosus HPr-expressing colonies. The nucleotide sequence of this ptsH gene and its flanking regions was determined by the dideoxy-chain-termination technique. Upstream, the 264-bp open reading frame of the ptsH gene is flanked by a putative S. carnosus promoter structure and a putative ptsI gene downstream suggesting that ptsH gene is the first gene in the PTS operon of S. carnosus. Comparison of the amino acid sequence of S. carnosus HPr with the HPr sequence of Staphylococcus aureus (derived from peptide sequencing) showed a high degree of similarity. PMID- 1901793 TI - Differential effects of tumor necrosis factor on the growth and differentiation of neuroblastoma and glioma cells. AB - We have studied the effect of tumor necrosis factor (TNF-alpha) on transformed neural and glial-derived cell lines. TNF-alpha at physiological doses was able to arrest the growth and inhibit DNA synthesis of N103 neuroblastoma cells. This phenomenon was accompanied by a morphological cell differentiation characterized by the outgrowth of neurites. By contrast, TNF-alpha induced an increase in the growth rate of C6 glioma cells and upon cytokine addition a higher number of C6 cells were found in the S + G2 phase of the cell cycle. C6 cells did not show morphological changes under this treatment. Analogous results were obtained with IFN-gamma. These neurotrophic and mitogenic effects of TNF-alpha suggest a putative role of this cytokine in the regeneration of brain tissue upon brain injury. PMID- 1901794 TI - The role of microfilaments in the capping of epidermal growth factor receptor in A431 cells. AB - Capping of the EGF receptor (EGF-R) on the surface of suspended and adherent epidermoid carcinoma cells, A431, is studied. It was induced at 20 degrees C after treating cells with monoclonal antibody to the EGF receptor followed by the second antibody conjugated with FITC. Accumulation of cortical actin under the caps was detected by rhodamine-phalloidin. Destruction of the actin stress-fiber like bundles was observed during incubation of cells with the ligands at 0 degrees C. Two processes appear to take place at 20 degrees C: redistribution of the EGF-R with cortical actin into the caps within 15-30 min and reconstruction of cytoplasmic actin bundles over 45-60 min. Dihydrocytochalasin B prevented cap formation in adherent cells, but small patches of EGF-R colocalized with actin aggregates under plasma membrane were observed. The function of different actin containing cytoskeleton structures in the process of capping is discussed. PMID- 1901795 TI - Modulation of growth-related gene expression and cell cycle synchronization by a sialoglycopeptide inhibitor. AB - When an 18-kDa cell surface sialoglycopeptide (SGP), isolated from intact bovine cerebral cortex cells, was incubated with exponentially growing Swiss 3T3 cells, cell proliferation was efficiently arrested. The inhibition was totally reversible since after removal of the SGP the arrested cells resumed their progress in the cell cycle in a synchronized manner for at least two divisions. Readdition of the GSP 4 h after reversal of the inhibition did not, however, affect the commitment of the cells to advance through metaphase, although progress through the cell cycle was once again inhibited after the cells reentered the G1 phase. The efficient nature of the SGP-mediated cell cycle arrest in G1 provided us with a basis to examine potential changes in the expression of several competence genes, and genes associated with mid and late G1, that have been implicated in cell cycle progression. Upon serum stimulation of quiescent Swiss 3T3 cells, the induction of c-myc and c-fos expression was not influenced by the SGP at concentrations highly inhibitory to cell cycling. Expression of JE was induced by serum, and the presence of the SGP had little effect on the expression of this growth-related gene. KC expression was not appreciably stimulated by serum although, surprisingly, the addition of the SGP resulted in a significant increase in expression. In addition, we learned that the SGP did not alter expression of ornithine decarboxylase, c-ras, or thymidine kinase, which are induced later than the genes associated with the initial stages of competence. PMID- 1901796 TI - Synthesis of sperm-specific basic nuclear proteins (SPs) in cultured spermatids from Xenopus laevis. AB - The accumulation and synthesis of sperm-specific basic nuclear proteins (SPs) in Xenopus spermatids in vitro were studied by acid-urea-Triton polyacrylamide gel electrophoresis and fluorography. In synchronous cultures of round spermatids, the amount of SP2 and SP3-5 accumulated almost linearly with time, while that of SP1 remained almost constant. Fluorography showed that round spermatids incorporated [14C]arginine mostly into SP1 and SP3-5, very little into SP2, and none into histones. When [14C]arginine was incorporated into cells for 24 h on Days 0, 3, and 6, followed by immediate extraction of basic nuclear proteins, the SP1 band was detected faintly on Day 0 and the intensity increased to the maximum level by Day 3 and remained constant on Day 6; the SP3-5 bands were first detected on Day 3 and their intensity increased by Day 6. Thus, SP1 and SP3-5 were synthesized differentially during the culture period. When [14C]arginine or [14C]lysine was incorporated into round spermatids on Days 0, 3, and 6 for 15 h and chased for 3-12 days, the intensity of the SP2 band increased significantly, while the intensity of the SP1 band decreased concomitantly. This result indicates that SP2 was processed from a precursor protein which is probably SP1. PMID- 1901797 TI - Epithelial cell-substrate adhesion in the cornea: localization of actin, talin, integrin, and fibronection [corrected]. AB - During corneal wound healing, epithelial cells migrate and spread over a basement membrane to cover the denuded area. We have initiated studies on the proteins involved in this cell-substrate interaction. In the present report, we show the distribution of actin, talin, integrin and fibronectin in the unwounded chicken corneal epithelium. Rhodamine-phalloidin and antibodies against talin, the beta subunit of integrin, and fibronectin were used to fluorescently label semi-thin cryosections of chicken cornea. Phalloidin labeling indicated the presence of f actin around the boundaries of all epithelial cells. Antitalin labeled the most basal aspect of the basal cells. Diffuse cytoplasmic labeling of the basal cells was also seen. Integrin was detected by the polyclonal anti-CSAT and monoclonal 30B6 antibodies. With both antibodies, the basal cells were outlined by label. These cells were similarly labeled by antifibronectin. Less distinct labeling of fibronectin was present around the boundaries of the outer epithelial cells. Our results indicate that many of the proteins associated with cell-substrate adherens junctions in other systems are also present in cell-substrate adhesion of the corneal epithelium. Details of the distribution of some of the proteins appear to be somewhat unusual, however. PMID- 1901798 TI - Contribution from a pH- and tonicity-sensitive K+ conductance to toad translens short-circuit current. AB - Studies of toad (Bufo marinus) lenses mounted in Ussing-type chambers revealed that: (1) the translens short-circuit current (Isc) across the posterior surface is primarily carried by the movement of Na+ from the posterior bathing solution to the lens; (2) across the anterior face the majority of the Isc is mediated by Ba(2+)-sensitive channels and the remaining current is rapidly reduced by ouabain; (3) most of the anterior K+ conductance is of the tonicity-sensitive, quinidine-inhibitable type (i.e. hypotonic shifts increase Isc and hypertonic shifts decrease Isc; quinidine pretreatment eliminates such responses); (4) 86Rb+ uptake is stimulated by alkaline pH and occurs primarily across the anterior surface with quinidine the most potent inhibitor of this process; and (5) the Na(+)-K+ pump can maintain lens [Na+] and [K+] for at least 20 hr in a Ringer's solution near neutral pH but not at pH 8.7 (a pH used in some studies with this lens). It is concluded that the Isc can be viewed as a representation of the current across the epithelial basolateral membrane, a surface dominated by pH- and tonicity-sensitive K+ channels. The direction of the Isc response to tonicity changes suggests a role for these channels in epithelial volume regulation. PMID- 1901799 TI - Paragonimus ohirai: immunobiochemical characterization on the tegumental glycocalyx of excysted juvenile recognized by a monoclonal antibody. AB - The tegumental glycocalyx of excysted juvenile (EJ) of Paragonimus ohirai was immunobiochemically characterized using a monoclonal antibody (MS-Mab). HPLC gel filtration showed that the antigens detected by two-site ELISA had a molecular weight of greater than or equal to 2 x 10(6) Da (dextran marker). On reduced SDS PAGE, the glycocalyx antigen retained in the stacking gel was cleaved into several much smaller antigens after pronase treatment. The antigenic activity of the glycocalyx was stable in two-site ELISA to heat and acid treatments, but sensitive to alkali, periodate, base/borohydride, and pronase treatments. Precipitin formation in immunodouble diffusion between MS-Mab and EJ crude antigen was inhibited only by two monosaccharides: galactose and N acetylgalactosamine. The purified glycocalyx bound strongly to PNA lectin, fairly well to RCA120 lectin, and slightly to SBA lectin, but not to Con A, WGA, UEA-1, DBA, or LFA lectins. Exo-beta-galactosidase treatment increased SBA binding, whereas it decreased PNA binding. PNA was observed to strongly bind to the body surface of living EJ. The antigenic activity of the glycocalyx was remarkably lost by incubation with exo-beta-galactosidase and O-glycanase. The glycocalyx was reactive with sera of P. ohirai-infected rats, and its reactivity was remarkably reduced by O-glycanase treatment. The ELISA level was higher in sera at an early stage of infection than in a late one. These studies show that the EJ tegumental glycocalyx is antigenic in infection, a marked, high molecular weight glycoprotein containing antigenic O-linked sugars, and that the sugar epitope is at the nonreducing terminal of the O-linked sugars and is composed of galactose and N-acetylgalactosamine. PMID- 1901800 TI - Tyrosine phosphorylation of human urokinase-type plasminogen activator. AB - Immunoblotting analysis of purified human urokinase plasminogen activator (u-PA), gives a positive signal when reacted with anti-phosphotyrosine monoclonal antibodies (MoAb anti-P-Tyr); competition with o-phospho-DL-tyrosine (P-Tyr) but not o-phospho-DL-threonine or serine (P-Treo, P-Ser) completely suppresses this signal. Either the 55 kDa u-PA form and the lower Mw form (33 kDa) derived from the 55 kDa u-PA are Tyr-phosphorylated also the u-PA secreted in the culture media of human fibrosarcoma cells (HT-1080) is phosphorylated in tyrosine as well as u-PA present in tissue extracts of tumors induced in nude mice by HT-1080 cells. These data show that urine purified human u-PA and u-PA produced by human fibrosarcoma cells, in vitro and in vivo, are phosphorylated in tyrosine; furthermore our data show that u-PA is the major Tyr-phosphorylated protein present in these human tumor cells. PMID- 1901801 TI - Stabilization of clathrin coated vesicles by amantadine, tromantadine and other hydrophobic amines. AB - Amantadine and related compounds stabilized the structure of purified pig brain clathrin coated vesicles (CCV) at biologically relevant concentrations. Incubation of purified CCV for 30 min at 25 degrees C or 37 degrees C caused the release of clathrin, as determined by a centrifugation assay, and a reduction in the number of coated vesicles, by electron microscopy. Amantadine (10 mM), tromantadine (1 mM), amidine D295 (cyclohexylcarboximidamide-(N benzyl)hydrochloride (10 mM), chloroquine (0.1 mM) and monodansylcadaverine (10 mM) significantly reduced the extent of dissociation. PMID- 1901802 TI - Role of glycine-82 as a pivot point during the transition from the inactive to the active form of the yeast Ras2 protein. AB - Ras proteins bind either GDP or GTP with high affinity. However, only the GTP bound form of the yeast Ras2 protein is able to stimulate adenylyl cyclase. To identify amino acid residues that play a role in the conversion from the GDP bound to the GTP-bound state of Ras proteins, we have searched for single amino acid substitutions that selectively affected the binding of one of the two nucleotides. We have found that the replacement of glycine-82 of the Ras2 protein by serine resulted in an increased rate of dissociation of Gpp(NH)p, a nonhydrolysable analog of GTP, while the GDP dissociation rate was not significantly modified. Glycine-82 resides in a region that is highly conserved between the yeast and human proteins. However, this residue is structurally distant from residues that participate in the binding of the nucleotide, as determined from the crystal structure of the human H-ras gene product. Therefore, the ability of the nucleotide binding site to discriminate between GDP and GTP is dependent not only on residues that are spatially close to the nucleotide, but also on distant amino acids. This is in agreement with the role of glycine-82 as a pivot point during the transition from the GDP- to the GTP-bound form of the Ras proteins. PMID- 1901803 TI - Site-directed mutagenesis of bovine pancreatic ribonuclease: lysine-41 and aspartate-121. AB - Chemical modification studies suggest that two residues of bovine pancreatic ribonuclease A (RNase A), Lys-41 and Asp-121, are important for catalysis. Three mutants of RNase A have been prepared, two point mutants with Lys-41 altered to Arg-41 and Asp-121 altered to Glu-121, and a double mutant where both residues are altered. The Lys-41 Arg mutant has ca. 2% the catalytic activity (kcat/Km) of the native protein, while the Asp-121Glu mutant has ca. 17% the catalytic activity of the native protein. The double mutant has catalytic activity comparable to the Lys-41Arg mutant. PMID- 1901804 TI - Complete 1H and 13C assignment of Lys and Leu sidechains of staphylococcal nuclease using HCCH-COSY and HCCH-TOCSY 3D NMR spectroscopy. AB - Complete proton and carbon sidechain assignments are reported for 22 lysine and 11 leucine residues in staphylococcal nuclease, an enzyme with 149 residues. These assignments are readily obtained in a direct manner from the correlations observed in the 3D HCCH-COSY and HCCH-TOCSY spectra and the known protein backbone assignments. These assignments open the way to detailed studies of the sidechain structure and dynamics at the active site, in the hydrophobic core and on the surface of the protein. PMID- 1901805 TI - EC-collaborative study on the determination of aflatoxin B1 in animal feeding stuffs. AB - A collaborative study was conducted to test a method, proposed in the European Community (EC) as a candidate-official method for the determination of aflatoxin B1 in compounded feeding stuffs. The study was undertaken on behalf of the European Commission's Community Bureau of Reference (BCR). It involved 25 laboratories from 11 EC countries. The method, based on chloroform extraction and Sep-Pak Florisil and C18 cartridge clean-up, offered either reverse-phase high performance liquid chromatography (HPLC) with iodine post-column derivatization, or two-dimensional thin-layer chromatography (TLC) as determinative steps. In the study, 22 laboratories applied HPLC, three laboratories applied TLC. The study involved six unknown samples. These consisted of blind duplicate samples of compounded feeding stuff, with target concentrations of aflatoxin B1 at less than 2, 8 and and 14 micrograms/kg. Statistical analysis of the HPLC data was carried out according to ISO 5725. For the less than 2 micrograms/kg sample, all reported aflatoxin concentrations were less than 2 micrograms/kg. At the 8 and 14 micrograms/kg level (pooled), repeatability (r) and reproducibility (R), expressed as ratios, were 1.4 and 1.7 respectively, and within-laboratory and between-laboratory coefficients of variation were 11% and 18% respectively. The study revealed that admittance of daylight in the laboratory caused losses of aflatoxin B1 and must be avoided. New glassware coming into contact with aqueous solutions containing aflatoxin B1 was found to be a potential cause of loss of aflatoxin B1. The method has been recommended to the European Commission to be considered for adoption in EC regulations. PMID- 1901806 TI - Purification and characterization of human testis aldose and aldehyde reductase. AB - 1. Aldose reductase and aldehyde reductase were purified to homogeneity from human testis. 2. The molecular weight of aldose reductase and aldehyde reductase were estimated to be 36,000 and 38,000 by SDS-PAGE, and the pI values of these enzymes were found to be 5.9 and 5.1 by chromatofocusing, respectively. 3. Aldose reductase had activity for aldo-sugars, whereas aldehyde reductase was virtually inactive for aldo-sugars. The Km values of aldose reductase for D-glucose, D galactose and D-xylose were 57, 49 and 6.2 mM, respectively. Aldose reductase utilized both NADPH and NADH as coenzymes, whereas aldehyde reductase only NADPH. 4. Sulfate ion caused 3-fold activation of aldose reductase, but little for that of aldehyde reductase. 5. Sodium valproate inhibited significantly aldehyde reductase, but not aldose reductase. Aldose reductase was inhibited strongly by aldose reductase inhibitors being in clinical trials at concentrations of the order of 10(-7)-10(-9) M. Aldehyde reductase was also inhibited by these inhibitors, but its susceptibility was less than aldose reductase. 6. Reaction of aldose reductase with pyridoxal 5'-phosphate (PLP) resulted ca 2.5-fold activation, but aldehyde reductase did not cause the activation. PLP-treated aldose reductase has lost the susceptibility to aldose reductase inhibitor. PMID- 1901807 TI - G proteins and modulation of insulin secretion. AB - Guanine nucleotide-binding proteins (G proteins) are critically important mediators of many signal-transduction systems. Several important sites regulating stimulus-secretion coupling and release of insulin from pancreatic beta-cells are modulated by G proteins. Gs mediates increases in intracellular cAMP associated with hormone-induced stimulation of insulin secretin. Gi mediates decreases in intracellular cAMP caused by inhibitors of insulin secretion, e.g., epinephrine, somatostatin, prostaglandin E2, and galanin. G proteins also regulate ion channels, phospholipases, and distal sites in exocytosis. Cholera and pertussis toxins irreversibly ADP ribosylate G proteins and are important tools that can be used both to manipulate G-protein-dependent modulators of insulin secretion and detect and quantify G proteins by electrophoretic techniques. The stage is set to pursue these initial observations in greater depth and ascertain whether G protein research will provide important new insights into normal and abnormal regulation of insulin secretion. PMID- 1901808 TI - Clinical and neurophysiological studies of aldose reductase inhibitor ponalrestat in chronic symptomatic diabetic peripheral neuropathy. AB - Increased flux through the polyol pathway mediated by the enzyme aldose reductase may be associated with the development of diabetic neuropathy. Fifty-four diabetic patients (median age 56 yr, range 25-65 yr) with chronic neuropathic symptoms were randomly allocated to placebo or aldose reductase inhibition (300 or 600 mg ponalrestat ICI 128436) groups for 24 wk. Patients with vibration perception thresholds (VPTs) greater than 35 V at the great toe or thermal difference thresholds (TTs) greater than 10 degrees C on the dorsum of the foot were excluded from the trial. No significant changes were observed in symptoms of pain, numbness, or paresthesia between ponalrestat and placebo groups, and there were no improvements in VPT or TT at several sites. Posterior tibial nerve conduction velocity changed from 35.3 +/- 4.9 m/s at baseline to 33.4 +/- 4.0 m/s at 24 wk (NS) with placebo compared with 37.6 +/- 5.6 vs. 37.2 +/- 8.7 m/s (NS) with 300 mg ponalrestat and 34.5 +/- 6.1 vs. 36.2 +/- 6.8 m/s (NS) with 600 mg ponalrestat. Further studies are indicated with intervention at an earlier stage in the evolution of neuropathy and for longer periods. PMID- 1901810 TI - Retention of composite inlays in enamel dentin cavities. AB - The retention of composite inlays depends on acid-etching of marginal enamel of the preparation. In many cases, only little marginal enamel is available, making loss of retention a liability. The present study evaluated the retention of three brands of composite inlays under various conditions. Inlays were fabricated and cemented in standardized enamel/dentin cavities prepared in extracted human teeth. The force necessary to extract a cemented inlay was used to express the retention of the inlay. The effects of thermocycling and choice of dentin-bonding agent on inlay retention were also determined. Inlays made of Estilux posterior C VS were more retentive than inlays of either Brilliant or SR-Isosit. The latter two products were found to provide similar retentive strengths. The retention of Estilux posterior C VS and SR-Isosit inlays declined when samples were thermocycled. Treatment with Gluma increased retention of inlays, resulting in retentive strengths of the same magnitude for all three inlay systems. The choice of dentin-bonding agent was found to affect composite inlay retention to a greater extent than the choice of either composite brand, mode of inlay curing, or effect of thermocycling. PMID- 1901809 TI - Nutrition and somatomedin. XXIII. Molecular regulation of IGF-I by amino acid availability in cultured hepatocytes. AB - The poor growth associated with protein-calorie malnutrition occurs despite circulating growth hormone levels that are normal or elevated and is thought to be mediated partly by blunted generation of insulinlike growth factor I (IGF-I) in the liver. To explore underlying mechanisms, we asked whether altered availability of amino acids could regulate hepatic IGF-I release independent of the contributions of regulatory hormones. Normal rat hepatocytes were isolated by collagenase digestion and maintained in serum-free medium with fixed concentrations of insulin and dexamethasone. Levels of immunoassayable albumin and IGF-I accumulation in daily changes of medium were sustained for 3-5 days, and all studies were performed within this period. Cellular viability and content of DNA were unaffected by deprivation of the essential amino acids lysine or tryptophan and the nonessential amino acids cysteine and/or cystine. However, deletion of tryptophan or lysine from the culture medium led to 63 and 76% declines in IGF-I release, respectively (both P less than 0.001 vs. complete medium), although omission of cysteine or cysteine plus cystine produced no significant change. Over 5 days of culture, release of albumin was maintained in complete medium, but omission of tryptophan depressed albumin release over days 2 5 (P less than 0.001). In complete medium, IGF-I release rose for 3 days and then declined. In tryptophan-deficient medium, IGF-I levels were comparable to control values after 24 h but did not rise at 48 h and then fell rapidly after 72 h in culture, with values significantly below levels in complete medium (all P less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1901811 TI - In vitro abrasion resistance and hardness of glass-ionomer cements. AB - The aim of this study was to compare the abrasion resistance and surface hardness of four glass-ionomer cements. The effects of hydration and dehydration on wear resistance were also studied. A composite material, enamel, and dentin were used as controls. For wear testing, the specimens were abraded on abrasion discs under water. All glass ionomers showed greater wear than composite and enamel, but less wear than dentin. Ketac-Fil showed the highest and Ketac-Silver the lowest wear resistance. Hydration or dehydration of the specimens did not significantly influence the wear rate of conventional glass ionomers, but the wear resistance of Ketac-Silver was increased due to dehydration. Ketac-Fil had the highest and Ketac-Silver the lowest hardness rating of the glass ionomers. The cement material did not show abrasion resistance better than that of the conventional glass ionomers, as has previously been suggested. PMID- 1901812 TI - Creep behavior of glass-ionomer restorative materials. AB - The creep of microspecimens of five glass-ionomer filling materials and one glass ionomer-cermet cement was studied by means of a torsional creep apparatus. The glass-ionomer specimens were aged one week and conditioned in 37 degrees C water. Shear stress of 2.47 x 10(-4) N.m was maintained for three h, and recovery was followed for 50 h. Creep curves were obtained at 21, 37, and 50 degrees C. The effect of temperature increase was studied. All the glass ionomers exhibited linear visco-elastic behavior at low deformations. Their shear moduli and resistance to creep were similar to those of some composites measured by the same method. The increase of temperature influenced the creep behavior and moduli of the materials (i.e., increased creep and residual strains and decreased shear modulus). Although the applied torque was very small, there was permanent deformation, the result of viscous flow in all experiments which was more pronounced at 50 degrees C. PMID- 1901813 TI - Hydrostatic intrapulpal pressure and bond strength of bonding systems. AB - The purpose of this study was to evaluate the effect of intra-pulpal pressure on shear bond strength of three light-cured glass-ionomer cements (GC lining cement, Vitrabond, and Zionomer) and four dentin bonding agents [Gluma/Scotchbond, Scotchbond 2, MBL, and Clearfil Photo Bond]. Buccal dentin surfaces were prepared just below the DEJ by means of a diamond bur. Dentin treatments were made for Zionomer (Zionomer conditioner), Scotchbond 2 (Scotchprep), MBL (10-3 solution), Clearfil PB (H3PO4), GC lining cement (Polyacrylic acid), and Gluma/Scotchbond (EDTA). Resin composites were inserted into tubes, positioned on dentin, cured, tested after five min or 24 h, and compared with samples bonded and stored under an intra-pulpal pressure of 36 cm of saline. After 24 h in superficial dentin, intrapulpal pressure reduced the bond strength only in MBL, Scotchbond 2, and Zionomer. Clearfil PB bond strength was increased, while Vitrabond, GC lining cement, and Gluma/Scotchbond were unaffected by the presence of pulpal pressure. However, in deep dentin, Scotchbond 2 and Clearfil PB shear bond strengths were significantly reduced by storage in the presence of 36-cm H2O pulpal pressure. Only Vitrabond remained unaffected by pulpal pressure in deep dentin. PMID- 1901814 TI - Photocure bonding agent containing phosphoric methacrylate. AB - Effective photocure phosphoric methacrylate bonding agents which bonded a dental composite to tooth substrates were proposed. Methacryloyloxydecyl phosphoric acid (MDP) or 2-methacryloyloxyethyl phenyl phosphoric acid (Phenyl-P) was dissolved in triethyleneglycol dimethacrylate (TEGDMA) with camphorquinone (CQ) and N phenylglycine (NPG). The combination of CQ and NPG was a good visible-light initiator for the polymerization. The highest bond strength was 5 MPa to dentin and 10 MPa to enamel when the adhesive contained Phenyl-P in TEGDMA. Dentin and enamel were recommended for demineralization with an aqueous mixture of 0.3 mol/L EDTA diammonium salt and 0.2 mol/L EDTA ammonium iron salt for generation of better bond strength. PMID- 1901815 TI - Evidence for balanced linkage of X chromosome polygenes in a natural population of Drosophila. AB - Extensive levels of polygenic variation can be maintained in a population without creating a severe segregational load. One way to account for this is that the alleles are arranged on a chromosome so that different regions balance each other phenotypically. To test whether this occurs in a natural population, we isolated ten Drosophila melanogaster X chromosomes and mapped regions of polygenic activity affecting sternopleural bristle number. The chromosomes fell into a small number of groups based upon the similarity of their distributions of polygenic activity. The results are consistent with a model in which a large proportion of the variation can be attributed to a small number of segregating chromosome regions and in which the chromosomes show internal balance. PMID- 1901816 TI - The doublesex locus of Drosophila melanogaster and its flanking regions: a cytogenetic analysis. AB - The region of the third chromosome (84D-F) of Drosophila melanogaster that contains the doublesex (dsx) locus has been cytogenetically analyzed. Twenty nine newly induced, and 42 preexisting rearrangements broken in dsx and the regions flanking dsx have been cytologically and genetically characterized. These studies established that the dsx locus is in salivary chromosome band 84E1-2. In addition, these observations provide strong evidence that the dsx locus functions only to regulate sexual differentiation and does not encode a vital function. To obtain new alleles at the dsx locus and to begin to analyze the genes flanking dsx, 59 lethal and visible mutations in a region encompassing dsx were induced. These mutations together with preexisting mutations in the region were deficiency mapped and placed into complementation groups. Among the mutations we isolated, four new mutations affecting sexual differentiation were identified. All proved to be alleles of dsx, suggesting that dsx is the only gene in this region involved in regulating sexual differentiation. All but one of the new dsx alleles have equivalent effects in males and females. The exception, dsxEFH55, strongly affects female sexual differentiation, but only weakly affects male sexual differentiation. The interactions of dsxEFH55 with mutations in other genes affecting sexual differentiation are described. These results are discussed in terms of the recent molecular findings that the dsx locus encodes sex-specific proteins that share in common their amino termini but have different carboxyl termini. The 72 mutations in this region that do not affect sexual differentiation identify 25 complementation groups. A translocation, T(2;3)Es that is associated with a lethal allele in one of these complementation groups is also broken at the engrailed (en) locus on the second chromosome and has a dominant phenotype that may be due to the expression of en in the anterior portion of the abdominal tergites where en is not normally expressed. The essential genes found in the 84D-F region are not evenly distributed throughout this region; most strikingly the 84D1-11 region appears to be devoid of essential genes. It is suggested that the lack of essential genes in this region is due to the region (1) containing genes with nonessential functions and (2) being duplicated, possibly both internally and elsewhere in the genome. PMID- 1901817 TI - Mapping point mutations in the Drosophila rosy locus using denaturing gradient gel blots. AB - Mutations within the rosy locus of Drosophila were mapped using blots of genomic DNA fragments separated on denaturing gradient gels. DNA sequence differences between otherwise identical small rosy DNA fragments were detected among the mutants as mobility shifts on the blots. Mutations were mapped to within a few hundred base pairs of rosy sequence in 100 of 130 mutants tested--a 77% detection rate. The sequence changes in 43 rosy mutations are presented; all but six of these were single base changes. Thirty-four of 36 sequenced mutations induced by the alkylating agents N-ethyl-N-nitrosourea and ethyl methanesulfonate were transitions. All of the mutations mapped in the rosy transcription unit. Twenty three of the 43 sequenced mutations change the predicted rosy gene polypeptide sequence; the remainder would interrupt protein translation (17), or disrupt mRNA processing (3). PMID- 1901819 TI - Changes in relative fitness with temperature among second chromosome arrangements in Drosophila melanogaster. AB - Development time and body weight of In(2L)t, R (a putative short inversion on the left arm of the second chromosome) and ST (standard) karyotypes of Drosophila melanogaster were measured at different temperatures. Frequency changes were followed in populations polymorphic for In(2L)t and ST and kept under different environmental conditions. These experiments were carried out in order to explain the worldwide latitudinal clines for In(2L)t and other inversions. To avoid interactions with the Adh and alpha Gpdh loci, which also have latitudinal clines, all karyotypes were homozygous AdhS alpha GpdhF. In(2L)t homokaryotypes had a longer development time and a lower weight than the other karyotypes at all temperatures. R/ST heterokaryotypes had the shortest development time and ST/ST had the smallest weight decrease with increasing temperature. The differences among the In(2L)t and ST karyotypes in development time were further analyzed in an experiment where the age at which 50% of the larvae were able to become adults, without further food ingestion, was determined. In polymorphic populations at 20 degrees and 25 degrees a significant decline of In(2L)t frequencies was observed. At 29.5 degrees and 33 degrees there was no change in In(2L)t frequencies but a significant excess of heterokaryotypes occurred. On ethanol-supplemented food the most drastic decline in In(2L)t frequency was observed. Populations transferred at 2- and 3-week intervals at 25 degrees exhibited large differences in final In(2L)t frequencies. The frequency changes could in part be attributed to the differences in development time and to previously observed differences in high temperature resistance. The experiments prove that the karyotypes are under selection. The results are discussed in relation to the geographic distribution of In(2L)t. PMID- 1901818 TI - Molecular characterization of eag: a gene affecting potassium channels in Drosophila melanogaster. AB - Genes encoding proteins involved in the function of the nervous system can be identified via mutations causing behavioral abnormalities. An example is ether a go-go (eag) in Drosophila melanogaster, which was identified originally as an X linked mutation that displayed ether-induced leg-shaking behavior. Electrophysiological and genetic evidence suggests that the product of the eag locus is intimately involved in the normal functioning of one or more types of voltage-gated potassium channels. To initiate a molecular analysis of eag we first generated a collection of deletions to pinpoint its cytological location. On the basis of this location, we identified an existing inversion, In(1)sc29, with one breakpoint at the eag locus and the other in the scute (sc) complex. A genomic library was prepared from In(1)sc29 and screened with a genomic DNA fragment that spanned the sc breakpoint to isolate DNA from the eag region. Beginning from this starting point over 85 kb of DNA were isolated by chromosome walking. Three additional eag alleles, including two dysgenesis-induced insertion mutations and a gamma-ray-induced insertional translocation, were located on the molecular map of the eag locus by Southern blot analysis. The molecular defects associated with these alleles encompass a total of 27 kb within the chromosome walk. A 10-kb transcript derived from this region, which is expressed most abundantly in heads, was identified on Northern blots. Two different eag mutations separated by over 20 kb interrupt the same transcript identifying it as the likely eag message. cDNAs representing a portion of this transcript have been isolated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1901820 TI - Ferredoxin and ribosomal protein S10 are encoded on the cyanelle genome of Cyanophora paradoxa. AB - The petF and rsp10 genes of the cyanellar genome of the taxonomically ambiguous flagellate Cyanophora paradoxa have been cloned, mapped, and sequenced. In higher plants these genes are not encoded in the chloroplast DNA, but are encoded in the nucleus. The C. paradoxa petF gene predicts a protein of 99 amino acids (aa) which is more similar to type-I ferredoxins of diverse cyanobacteria than to those of green algae, dinoflagellates, and higher plants. The rsp10 gene (rspJ) predicts a protein of 105 aa which is about 50% identical and 71% homologous to the proteins of Escherichia coli and Mycoplasma capricolum. The results are discussed within the context of the endosymbiotic origins of chloroplasts from cyanobacteria. PMID- 1901821 TI - Genes encoding a mouse monoclonal antibody are expressed in transgenic mice, rabbits and pigs. AB - To study the expression pattern of immunoglobulin-encoding genes in transgenic animals, we have introduced the genes for the light and heavy chain of a mouse monoclonal antibody (mAb) into the germ-line of mice (control), rabbits and pigs. The transgenes were detected in the mouse lines, two rabbit lines and pigs. Titers of 100-200 micrograms mAb/ml (rabbits) and up to 1000 micrograms mAb/ml (pig) were measured in the sera of the transgenic animals. Isoelectric focusing experiments with serum followed by immunofixation revealed that in the transgenic pig only a minority of the bands were identical to those of the purified mouse mAb. In transgenic rabbits we found no coincidence of bands at all. The results can be explained by assuming tissue- and cell-type-specific glycosylation, modification and possible heterologous chain associations. Expression of Ab in the serum of animals could help to protect against diseases (e.g., influenza in pigs). PMID- 1901822 TI - Construction and expression of an adenosine deaminase::lacZ fusion gene. AB - A eukaryotic expression vector was constructed in which the coding nucleotide sequences (ADA) of human adenosine deaminase (ADA) were fused in frame with the coding sequences of the bacterial gene lacZ encoding beta-galactosidase (beta Gal). This ADA::lacZ fusion gene was anticipated to encode a hybrid protein that has retained the biological functions of both proteins. Transfection of mammalian cells with the fusion gene resulted in the synthesis of both ADA and beta Gal. Cells expressing the gene could therefore be detected with the histochemical staining procedure that relies on the conversion of the indicator, XGal, by beta Gal. In addition, the transfected cells could be sorted on a fluorescence activated cell sorter with the use of a vital staining procedure described for the selection of beta Gal-producing cells. Cell lines that harbored the fusion gene were tested for ADA overexpression by exposing them to the cytotoxic adenosine analog 9-beta-D-xylofuranosyl adenine (Xyl-A), in the presence of the ADA inhibitor deoxycoformycin (dCF). Resistance to Xyl-A/dCF was observed in the lines carrying ADA::lacZ and moreover, the fraction of cells that survived a stringent selection for ADA overexpression also exhibited significantly increased levels of beta Gal, which confirmed the direct linkage between ADA and lacZ expression. The use of this and other fusion genes might be useful in the development of gene-therapy protocols where they could help to meet the demand for versatile methods to detect and select cells with newly introduced genes. PMID- 1901823 TI - "Enzymatic" lipid peroxidation: reactions of mammalian lipoxygenases. AB - Lipoxygenase is a dioxygenase which incorporates one molecule of oxygen at a certain position of unsaturated fatty acids such as arachidonic and linolenic acids. The enzymatic oxygenation of unsaturated fatty acids is stereospecific concomitant with a stereoselective abstraction of hydrogen atom. Fatty acid cyclooxygenase is an atypical lipoxygenase incorporating two molecules of oxygen, and initiates the biosynthesis of prostaglandins and thromboxanes. Arachidonate 5 lipoxygenase is responsible for the leukotriene synthesis. No such bioactive compound has been found as a metabolite of the 12- and 15-lipoxygenase pathways, and their physiological roles are still unclarified. These enzymes have been purified, and their molecular and catalytic properties have been investigated. Their cDNA clones have been isolated, and their nucleotide sequences have been determined deducing the primary structures of the enzymes. PMID- 1901824 TI - Restoration of myo-inositol uptake by aldose reductase inhibitor in human skin fibroblasts cultured in high-glucose medium. PMID- 1901825 TI - Changes of common fragile sites on chromosomes according to the menstrual cycle. AB - The frequencies of chromosomal breaks and sister chromatid exchanges (SCE) are influenced by pregnancy, oral hormonal contraceptives and the menstrual cycle. The changes in the number and sites of spontaneous and aphidicolin-induced breaks on chromosomes from peripheral blood lymphocytes during the menstrual cycle were examined in 8 healthy women. Menstrual cycle was determined by menstruation and the quantity of serum estrogen, progesterone and luteinizing hormone. The number of spontaneous breaks at the follicular phase, the interval phase (which includes ovulation) and the luteal phase were 3.1 +/- 1.1, 2.7 +/- 2.3 and 3.9 +/- 2.6 per 100 mitoses, respectively. The frequencies of aphidicolin-induced breaks in the same phases were 95.8 +/- 23.3, 90.6 +/- 14.3 and 122.7 +/- 20.1 per 100 mitoses, respectively. The higher frequency at the luteal phase was statistically significant compared with the other phases. In the luteal phase, bands 2q32, 3q27, 6q26 and 16q23 had higher frequencies of breaks (P less than 0.05); however, breaks at band 9q32 decreased significantly. SCE showed considerable variation, but with no statistical significance. PMID- 1901826 TI - Frequent deletions at Xq28 indicate genetic heterogeneity in Hunter syndrome. AB - Hunter syndrome is a human X-linked disorder caused by deficiency of the lysosomal exohydrolase iduronate-2-sulphatase (IDS). The consequent accumulation of the mucopolysaccharides dermatan sulphate and heparan sulphate, in the brain and other tissues, often results in death before adulthood. There is, however, a broad spectrum of severity that has been attributed to different mutations of the Hunter syndrome gene. We have used an IDS cDNA clone to localise the IDS gene to Xq28, distal to the fragile X mutation (FRAXA). One-third of Hunter syndrome patients had various deletions or rearrangements of their IDS gene, proving that different mutations are common in this condition. Deletions of the IDS gene can include a conserved locus that is tightly linked to FRAXA, suggesting that deletion of nearby genes may contribute to the variable clinical severity noted in Hunter syndrome. The cDNA clone was also shown to span the X chromosome breakpoint in a female Hunter syndrome patient with an X;autosome translocation. PMID- 1901828 TI - Hunter syndrome in Jews in Israel: further evidence for prenatal selection favoring the Hunter allele. AB - Among all the Jewish families with Hunter patients in Israel, 10 were Ashkenazi or Moroccan in origin. In those families, there was a paucity of new mutations. In addition, a significant deviation of the segregation ratio between the Hunter gene and the normal allele was demonstrated among the offspring of heterozygous mothers or siblings of affected children in these families. These results confirm and extend our previous observations suggesting selection in favor of the X chromosome carrying the Hunter allele among Ashkenazi and Moroccan Jews. PMID- 1901827 TI - The human aldose reductase gene maps to chromosome region 7q35. AB - The human aldose reductase (AR) gene has been mapped to chromosome 7 using the polymerase chain reaction to specifically amplify the human AR sequence in hamster/human hybrid DNA and also in mouse/human monochromosome hybrids. The assignment to chromosome 7 was confirmed by in situ hybridisation to human metaphase chromosomes using a novel, rapid hybridisation, method giving a regional localisation at 7q35. PMID- 1901829 TI - IL-4 acts as a homeostatic regulator of IL-2-induced TNF and IFN-gamma. AB - Interleukin-4 (IL-4) is a cytokine secreted by interleukin-2 (IL-2)-activated lymphocytes. IL-2-stimulated lymphocytes also secrete two cytokines, tumour necrosis factor (TNF) and gamma-interferon (IFN-gamma), which contribute to effector function and which may themselves recruit fresh, cytokine-secreting effector cells. We have now investigated whether the IL-4 induced is able to homeostatically regulate secretion of the TNF and IFN-gamma. Peripheral blood mononuclear cells or lymphocytes from normal donors and from patients with neoplastic disease were cultured in the presence of IL-2 alone, IL-4 alone or with both cytokines. IL-2 induced high levels of TNF and IFN-gamma secretion in both groups. The addition of recombinant IL-4 to these IL-2-stimulated cultures lead to significant inhibition of IFN-gamma and TNF production. IFN-gamma secretion was reduced by 50-99% in normal donors and by between 11% and 99% in patients (P less than 0.001). TNF levels induced by IL-2 were similarly reduced by IL-4 both in normal donors (P less than 0.003) and in patients (P less than 0.01). These inhibitory effects were produced by IL-4 at doses of IL-2 attainable in vivo. Inhibition appears to represent a homeostatic regulatory mechanism which may limit recruitment of fresh activated killer (AK) cells. When endogenous IL-4 activity in IL-2-activated lymphocytes was blocked by anti-IL-4 antibody, significantly higher levels of IFN-gamma and TNF were secreted (P less than 0.05). Since both TNF and IFN-gamma may contribute to the anti-neoplastic action of IL-2, manipulating the level of IL-4 activity in vivo could augment the benefits of IL-2 immunotherapy. PMID- 1901830 TI - The effect of class II gene transfection on the tumourigenicity of the H-2K negative mouse leukaemia cell line K36.16. AB - There is much evidence to suggest that potentially immunogenic tumour cells can escape cytolytic immune destruction by loss of class I antigen expression. Many tumours are allele-specific class I negative and, in murine systems, reconstitution of class I expression by gene transfection leads to an increase in tumour immunogenicity. In many systems where mice have rejected class I transfected tumour cells they are also immune to a subsequent challenge with the untransfected parent tumour. In this study we have examined the effect of stable class II antigen expression (induced by gene transfection) on a class I loss mutant (H-2Kk negative) murine cell line, K36.16. We show that H-2Ek expression is more effective at increasing tumour immunogenicity than the reconstitution of H-2Kk expression in these cells. This suggests that the induction of class II antigen expression on tumour cells may provide an effective way of enhancing tumour-specific immune responses in vivo. PMID- 1901831 TI - Clonal analysis of the relationship between class II MHC-restricted cytolysis and lymphokine secretion in murine L3T4+ T cells. AB - A panel of peptide-specific murine CD4+ T-cell clones was tested for lymphokine secretion, antigen-specific cytolysis and CD3-mediated cytolysis. The data indicated an imperfect correlation between Th1/Th2 status with regard to antigen specific cytolysis but also indicated that all the clones were cytotoxic when stimulated with anti-CD3 antibody. PMID- 1901832 TI - In vitro effects of polychlorinated biphenyls on human platelets. AB - Incubation of human platelets with polychlorinated biphenyls (PCB) induced and modulated cellular responses to a different degree. 3,3',4,4'-tetrachlorobiphenyl (TCB) was a more potent inducer of platelet aggregation, serotonin release and 12 HETE generation compared to the other PCB [2,2',3,3'-TCB,3,3'-dichlorobiphenyl (DCB),2,2',4,5,5'-pentachlorobiphenyl (PCB)]. 3,3',4,4'-TCB showed synergistic effects, in combination with other PCB, such as an enhanced formation of 12-HETE, when 3,3'-DCB and 2,2',3,3'-TCB were applied simultaneously. The combined incubation of platelets with PCB and sodium fluoride (NaF), an activator of G proteins, resulted in synergistic 12-HETE generation compared to stimulation with NaF or PCB alone. Furthermore, when platelets were incubated with the PCB the enzymatic steps controlling the metabolism of the platelet-activating factor (PAF) were modulated. A direct relationship between the extent of platelet activation and the chloro-substitution pattern of PCB exists. PMID- 1901834 TI - Tumor necrosis factor and interferon as prognostic markers in human immunodeficiency virus (HIV) infection. AB - Peripheral blood cells were obtained from patients at different stages of their human immunodeficiency virus (HIV) infection. It was found that the capacity to generate interferon alpha was reduced already at Walter Reed stage 2 (WR) while the interferon gamma capacity remained largely unaffected until WR stage 4. Endogenous tumor necrosis factor (TNF) alpha production increased as the HIV disease progressed. The data obtained add to our knowledge on destruction of the immune system by the HIV. Moreover TNF and acid labile interferon alpha might contribute to HIV replication and disease progression. Nevertheless the tests performed are too time-consuming to be introduced into routine analysis of HIV infection or for monitoring its therapy and can so far not be used for intervention strategies. Further studies are needed. PMID- 1901833 TI - Serological markers as prognostic criteria for the course of HIV infection. AB - 576 serum samples from 139 HIV infected patients were analyzed for the presence of HIV antigens, as well as anti-core, anti-env and neutralizing antibodies. The results were correlated with the clinical and immunological stages of the patients. While almost all sera were positive for anti-env antibodies, only two thirds of the same sera had antibodies to core proteins. The average antibody titres, particularly of anti-core antibodies, decreased with the onset of clinical symptoms. The presence of p24 antigen could be demonstrated in only 16% of the sera. A positive reaction for core antigen seemed to be correlated with the absence of anti-core antibodies. Env specific neutralizing antibodies were found to be present in all of the sera analyzed in the LC5-test with a maximum neutralizing capacity observed in sera from WR 4 patients. A useful serological marker must fulfil two criteria, namely positive reactivity in the majority of sera examined and a broad range of antibody titres. None of the above described parameters meet these demands. Here we describe the search for new antibody markers, for example antibodies directed against HIV regulatory proteins. PMID- 1901835 TI - A mannose receptor is involved in retinal phagocytosis. AB - A 175-kD mannose-specific receptor has been described in macrophages which appears to mediate pinocytosis and phagocytosis. A mannose-specific receptor has also been found on retinal pigment epithelial cells (RPE). Its role was examined in the phagocytosis of photoreceptor outer segments (ROS) by the RPE. All testing was done on cultured RPE cells challenged with fluorescein isothiocyanate (FITC) labeled ROS for 4 hr at 37 degrees C. Total (internalized and bound) and phagocytized (internalized) ROS were quantified, and the effects of several experimental conditions on ROS phagocytosis were examined. Incubation of RPE cells in the presence of rabbit anti-serum (1:100) raised against the rat alveolar macrophage mannose receptor (anti-Mr) showed a 80% reduction in ROS phagocytosis compared with RPE in the presence of ROS alone. Anti-Mr preabsorbed with purified human mannose receptor protein (4 micrograms) showed no reduction in ROS phagocytosis. Incubation of RPE with preimmune serum showed no reduction in ROS phagocytosis. When FITC-labeled ROS (1.8 X 10(7)) were preincubated with purified mannose receptor, there was a 93% reduction in phagocytosis. Immunoblots of solubilized rat RPE microvillus membranes stained with the anti-Mr showed a single stained band at the 175-kD region, and immunolocalization studies showed specific labeling along RPE microvilli. These results suggest that a mannose specific receptor is involved in retinal phagocytosis. PMID- 1901836 TI - Effect of aldose reductase inhibitors on naphthalene cataract formation in the rat. AB - Naphthalene feeding can result in cataract formation in rats and rabbits due to specific metabolites of naphthalene. The concomitant administration of the aldose reductase inhibitor Al1576 to naphthalene-fed rats was proven to prevent cataract formation. To determine whether this effect was directly linked to the ability of Al1576 to inhibit enzyme aldose reductase, a variety of structurally diverse aldose reductase inhibitors, including the carboxylic acids tolrestat, Ponalrestat, and FK366, and the spirohydantoins, sorbinil and Al1576, were investigated for their ability to inhibit naphthalene-induced cataracts. Brown Norway rats, administered naphthalene by gavage, were fed normal rat chow containing these aldose reductase inhibitors at levels known to inhibit sugar cataract formation. The lens changes in these rats were monitored over a 90-day period by portable slit-lamp microscopy and histologic study. Al1576 showed a dose-dependent reduction in naphthalene-induced cataract formation, with no naphthalene-associated deposits seen in toluidine blue-stained lens sections. Sorbinil also reduced lens changes, whereas tolrestat, Ponalrestat, and FK366 had no effect. These results suggest that inhibition of naphthalene-induced cataract formation by structurally diverse aldose reductase inhibitors was not linked to the inhibition of aldose reductase. PMID- 1901837 TI - Species and type phages of lactococcal bacteriophages. AB - Lactococcal phages are classified according to morphology and DNA homology. Phages are differentiated into 12 phage species, and type phages of each species are proposed. Members and possible members of each species are named. Available data on type phages are tabulated including morphology, DNA characteristics and phage protein bands. PMID- 1901838 TI - Incidence of and reasons for excluding patients with acute myocardial infarction from thrombolytic therapy. AB - The percentage of patients with acute myocardial infarction (AMI) who were eligible for thrombolytic therapy was evaluated prospectively, with analysis of the causes for exclusion, in 857 patients with AMI hospitalized in the Chaim Sheba Medical Center, Tel-Hashomer, in 1988. Thrombolytic therapy was given to 127 patients (14.8%); 99 patients were treated with tissue plasminogen activating factor and 28 patients received streptokinase. Three hundred and sixty patients (42.0%) were rejected because of age (greater than 72 years). Other reasons for exclusion were duration of pain lasting for more than 4 h (28.5%), unknown time of onset of the chest pain (9.7%), absence of ST elevation on admission ECG (8.1%), systemic hypertension (4.4%), and presence of severe congestive heart failure upon admission (10.1%). Restricting thrombolytic therapy only to patients less than 72 years old with chest pain duration of 4 h limits the impact of this treatment on the general welfare of patients with AMI. By raising the age limit and extending the time interval between pain onset and treatment initiation, adding newer indications, and enhancing public awareness for early arrival to hospital, the benefit of thrombolytic therapy may be made available to more patients with AMI. PMID- 1901839 TI - Comparison of two pre-admission testing methods for elective surgery patients. AB - Patients admitted for elective surgery (inguinal hernia, varicose veins and hemorrhoids) were studied in order to evaluate the impact of performing pre admission testing (PAT) by utilizing an automated multiphasic health testing (AMHT) technology on the rate of repeating the pre-operative routine laboratory tests during hospitalization. A slightly lower but statistically significant rate of repeated tests was found among patients who performed PAT by AMHTS compared with those who performed the tests via the conventional ambulatory system. This result suggests that performing routine tests before hospitalization in a single authorized AMHTS facility is preferred since it saves the patient time and reduces the need for repeated tests. PMID- 1901840 TI - Trauma case mix and hospital payment: the potential for refining DRGs. AB - Uniform hospital discharge abstract data from Maryland were used to examine the homogeneity of trauma-related DRGs with respect to a well-established measure of injury severity, the Injury Severity Score (ISS). Thirty DRGs were identified as including trauma cases with a wide range of severity; for each of these DRGs, ISS explains a significant amount of variation in length of stay. By applying statistical techniques similar to those used to create the original DRG groupings, these 30 DRGs were subdivided by severity and age categories to create a new set of severity-modified DRGs. The potential effects of using DRGs and modified DRGs to pay for inpatient care within the Maryland state regionalized system of trauma care were examined. Payments based on regional averages per DRG and per modified DRG were compared to actual hospital charges regulated by the state's Health Services Cost Review Commission. Using average charges per DRG as a basis of payment, approximately !1.4 million (11 percent of total hospital charges) would be shifted from trauma centers to nontrauma centers. This shift represents an 18 percent loss in revenues to trauma centers and a 30 percent gain in revenues to nontrauma centers. Using a payment system based on severity modified DRGs, trauma centers would still experience a net loss in revenues and the nontrauma centers a net gain, but the total amount of the shift would be reduced from $11.4 million to $9.8 million. The results argue for the need to explore alternative payment systems not strictly based on current DRGs. Because of DRGs do not adequately reflect severity differences, using them to pay hospitals will create financial incentives that discourage regionalization of trauma care. PMID- 1901842 TI - The effect of swine leukocyte antigen haplotype on birth and weaning weights in miniature pigs and the role of statistical analysis in this estimation. AB - Miniature pigs of seven swine leukocyte antigen (SLA) genotypes were examined for birth and weaning weights to determine the influence of major histocompatibility (MHC) and background genes on these traits. Effects of different statistical analyses on the magnitude of these associations also were examined. Data on 154 piglets from 32 litters were analyzed by least squares using a linear model that included effects of SLA, litter, and sex of piglet. In these miniature pigs, SLA genotype had little influence on birth and weaning weight; litter, which includes effects of background genes, had a significant effect on both birth weight (P less than or equal to .0001) and weaning (P less than or equal to .005) weight. When litter effects were not accounted for, SLA haplotype appeared to influence both birth (P less than or equal to .001) and weaning (P less than or equal to .10) weights. Use of simple group means, as opposed to least squares means, for comparisons of genotypes yielded misleading results. Simple means indicated that piglets with the aa genotype were heavier (P less than or equal to .01) at birth than those with the cd genotype; in contrast, least squares means showed that cd piglets were slightly heavier at birth (P less than or equal to .10). Heterosis was not observed for birth or weaning weights among piglets of various genotypes, nor did one vs two copies of any haplotype influence these traits. PMID- 1901841 TI - Ambulatory care groups: a categorization of diagnoses for research and management. AB - This article describes a case-mix measure for application in ambulatory populations. The method is based primarily on categorization of diagnoses according to their likelihood of persistence. Fifty-one combinations (the ambulatory care groups or ACGs) result from applying multivariate techniques to maximize variance explained in use of services and ambulatory care charges. The method is tested in four different HMOs and a large Medicaid population. The percentage of the population in each of the 51 categories is similar across the HMOs; the Medicaid population has higher burdens of morbidity as measured by more numerous types of diagnoses. Mean visit rates for individuals within each of the 51 morbidity categories are generally similar across the five facilities, but these visit rates vary markedly from one category to another, even within groupings that are similar in the number of types of diagnoses within them. Visit rates for individuals who stay in the same ACG were similar from one year to the next. The ACG system is found useful in predicting both concurrent and subsequent ambulatory care use and charges as well as subsequent morbidity. It provides a way to specify case mix in enrolled populations for research as well as administration and reimbursement for ambulatory care. PMID- 1901843 TI - Effect of human growth hormone-releasing factor and(or) thyrotropin-releasing factor on growth, carcass composition, diet digestibility, nutrient balance, and plasma constituents in dairy calves. AB - Sixty male dairy grain-fed calves, raised from 70 to 223 kg BW in individual crates, were used in a 2 X 2 factorial arrangement to determine the effect of administration of human growth hormone-releasing factor (1-29)NH2 (GRF) and(or) thyrotropin-releasing factor (TRF). Calves received twice-daily s.c. injections of .9% NaCl (control), GRF (5 micrograms/kg BW), TRF (1 micrograms/kg BW) or GRF (5 micrograms/kg BW) plus TRF (1 micrograms/kg GTRF). Average daily gain and days on feed were not affected by treatments, but TRF treatment increased (P less than .05) total intake of dry matter (DM) and feed conversion ratio: 3.00, 3.02, 3.08, and 3.22 kg DM/kg weight gain for control, GRF, TRF, and GTRF, respectively. During two 7-d periods, after 66 and 75 d of treatment, feces and urine were collected from 40 calves (5 per treatment per period). Treatment with GRF increased (P less than .05) digestibility of DM, nitrogen (N), and energy and tended (P less than .20) to increase N retention. At slaughter, withers height was increased (P = .05) by GRF and carcass length was increased (P less than .05) by TRF. Pituitary and liver weights were increased (P less than .05) by TRF. The combination of GRF and TRF slightly increased (P less than .10) protein content and decreased (P less than .05) fat content of the 9-10-11th rib section. After d 1, GRF treatment chronically increased (P less than .05) insulin concentrations and also increased (P less than .10) IGF-I concentrations on d 29 and 57. In summary, chronic treatment with GRF and(or) TRF did not improve growth or efficiency, although GRF increased digestibility of DM, N, and energy and the GRF plus TRF combination resulted in slightly leaner carcasses. PMID- 1901844 TI - Amino acid and energy interrelationships in pigs weighing 20 to 50 kilograms: I. Rate and efficiency of weight gain. AB - The relationships between dietary amino acids and DE for pigs weighing 20 to 50 kg were investigated in two experiments. In Exp. 1, there were three dietary lysine levels that were either adjusted (1.50, 2.35 and 3.20 g/Mcal DE) for five DE levels (3.00 to 4.00 Mcal/kg) or unadjusted (.45, .71 and .96% of the diet) for three DE levels (3.50 to 4.00 Mcal/kg). In Exp. 2, the effects of six lysine:DE ratios (1.90 to 3.90 g/Mcal) at two DE levels (3.25 and 3.75 Mcal/kg) were investigated. In both experiments, diets were formulated using a constant ratio of corn and soybean meal. Pigs (equal numbers of barrows and gilts) were housed and fed individually and had ad libitum access to feed and water. Digestible energy intake was not affected by energy content of the diets. In Exp. 1, lysine intake did not differ with DE in the adjusted diets but decreased (P less than .001) as DE increased in the unadjusted diets. Weight gain was relatively consistent and gain:DE intake increased (P less than .001) as DE increased in the adjusted diets, but both decreased (P less than .005) with increasing DE in the unadjusted diets. Both criteria increased (P less than .001) in response to higher lysine:DE in the adjusted and lysine in the unadjusted diets. In Exp. 2, weight gain increased (P less than .005), but there was no effect (P greater than .05) on gain:DE intake as DE increased. Both weight gain and gain:DE intake increased (P less than .001) and backfat decreased (P less than .01) as lysine:DE ratios increased. The results demonstrate the need to increase dietary amino acid levels in concert with increases in energy contents. Regression analyses indicated that weight gain and gain:DE intake for 20- to 50 kg pigs were maximized at approximately 3.0 g lysine/Mcal DE (or 49 g of balanced protein/Mcal DE). PMID- 1901845 TI - Amino acid and energy interrelationships in pigs weighing 20 to 50 kilograms: II. Rate and efficiency of protein and fat deposition. AB - Two experiments were conducted to investigate the relationships between amino acids and DE for pigs weighing 20 to 50 kg. In Exp. 1, there were three dietary lysine levels that were either adjusted (1.50, 2.35 and 3.20 g/Mcal DE) for five DE levels (3.00 to 4.00 Mcal/kg) or unadjusted (.45, .71 and .96% of the diet) for three DE levels (3.50 to 4.00 Mcal/kg). In Exp. 2, diets containing six lysine:DE ratios (1.90 to 3.90 g/Mcal) at two DE levels (3.25 and 3.75 Mcal/kg) were fed. Pigs were housed individually, and could eat and drink ad libitum. When pigs weighed 50 kg, their empty body composition was determined by the urea dilution technique in Exp. 1 and by prediction equations based on backfat in Exp. 2. For the adjusted diets in Exp. 1, protein deposition and protein deposition:DE intake increased (P less than .01) slightly as DE levels increased. These criteria decreased linearly (P less than .001), and fat deposition increased (P = .11) as DE increased when lysine:DE ratios were not maintained. As lysine levels increased, protein deposition and protein deposition: DE intake increased (P less than .001) in both the adjusted and unadjusted diets. In Exp. 2, there was no effect of DE on either the rate or efficiency of protein deposition. Both protein deposition and protein deposition:DE intake increased (P less than .001) and fat deposition decreased as lysine:DE ratios increased up to 3.00 g lysine/Mcal DE. Protein deposition: lysine intake decreased (P less than .01) progressively as the lysine:DE ratio increased. Regression analyses indicated the protein deposition increased up to 3.00 g lysine/Mcal DE. The results demonstrate the need to adjust lysine according to energy levels and indicate that the optimum ratio for protein deposition was approximately 3.00 g lysine/Mcal DE (or 49 g of balanced protein/Mcal DE). PMID- 1901846 TI - Nutrient digestibilities of soft winter wheat, improved triticale cultivars, and pearl millet for finishing pigs. AB - A replicated 4 x 4 Latin square digestion trial was conducted to determine apparent nutrient digestibilities and N and energy balances for soft red winter wheat, Beagle 82 triticale, Florico triticale, and pearl millet using finishing pigs fitted with ileal T-cannulas. Fortified experimental diets contained 97.5% of each respective grain. Nitrogen and amino acid digestibilities of soft winter wheat and triticale were similar (P greater than .13) when measured near the end of the small intestine and over the total digestive tract. Ileal digestibilities of alanine, isoleucine, leucine, threonine, tryptophan, and valine were higher (P less than .05) for pearl millet than for the other grains. Total tract N and amino acid digestibilities were all higher than ileal digestibilities. Gross energy and DM digestibilities determined at the small intestine were higher (P less than .05) for wheat and pearl millet than for Beagle 82 triticale, with the Florico variety being intermediate in energy digestibility. Total tract digestible and ME concentrations followed essentially the same pattern as ileal GE digestibility and were 2 to 3% higher (P less than .05) for wheat and pearl millet than Beagle 82 triticale. Florico triticale had similar (P greater than .05) DE but was 1.3% lower (P less than .05) in ME content than wheat. PMID- 1901847 TI - Follicle-stimulating hormone (FSH) during the secondary surge in gilts as influenced by administration of porcine follicular fluid (pFF). AB - The effect of volume and frequency of administration of porcine follicular fluid (pFF) on FSH concentration was determined in mature gilts during the period of the secondary FSH surge (d 0 to 5; d 0 = onset of estrus) and following withdrawal of pFF (d 5.5 to 9). Crossbred gilts (n = 14) were randomized in a 3 x 2 factorial treatment design involving three doses of pFF (0, 5, or 10 ml) and once- vs twice-daily pFF administration. Porcine FF was aspirated from medium and large follicles and treated with 5 mg of activated charcoal per milliliter of pFF to remove steroids. Once-daily administration of pFF, regardless of dose, failed to suppress mean concentrations of FSH during the secondary FSH surge. Treatment of gilts twice daily with 10 ml of pFF suppressed (P less than .05) area under the FSH curve during the secondary FSH surge compared with gilts given saline. Gilts treated twice daily with 5 ml pFF showed comparable suppression of plasma FSH from d 0 to 3 but began to overcome FSH inhibition after d 3. As a result, FSH release only tended to be lower than controls for the entire treatment period (P less than .1). Mean FSH concentrations were increased (P less than .05) during the post-treatment period (d 5.5 to 9) by treatment with intermediate (5 ml pFF, two times daily and 10 ml pFF, one time daily) and high (10 ml pFF, two times daily) doses of pFF. Neither ovulation rate nor interestrous interval was affected by pFF administration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1901848 TI - Concentrations of serum constituents in cold-stressed calves from heifers fed inadequate protein and(or) energy. AB - A study with neonatal calves was conducted to determine the effects of maternal crude protein (CP) and(or) metabolizable energy (ME) malnutrition, cold stress (0 or 21 degrees C), and age on concentrations of selected serum constituents. For each of 2 yr, 60 artificially bred Angus heifers were assigned randomly to a 2 x 2 factorial nutritional plan 150 d before predicted parturition. The diets provided each heifer with either .32 or .96 kg/d of CP and 8.7 or 12.6 Mcal/d of ME. Blood samples were obtained from heifers at parturition and from their calves at birth and at 12, 24, 36, 48, and 72 h of age. Sera were analyzed for concentrations of blood urea nitrogen (BUN), creatinine (Creat), iron, total protein (TProt), alkaline phosphatase (AlkPhos), total bilirubin (TBil), and cholesterol (Chol). Mean correlations of these constituents in calf sera between 12-h adjacency intervals were high, but those between longer times (48 or 60 h) were low. Simple correlations of serum constituents between cows and calves at birth were low except for BUN (r = .578 and .295 for yr 1 and 2, respectively). There were significant main treatment effects for maternal CP consumption on BUN levels, for environmental temperature on BUN, Creat, and TBil levels, and for years on BUN, Creat, iron, and AlkPhos levels in calves. Significant polynomial relationships were found over hours of age for all variables. Blood urea N decreased in normal calves but remained relatively constant at a low level in deficient calves. Year x hour of age interactions occurred for iron, TProt, AlkPhos, TBil, and Chol. Protein x year x hour of age interactions were found for iron and Chol. These results suggest that random sampling times are not useful for decision making during the first 72 h after birth. Consideration must be given to multiple samples taken at specific calf ages, to environmental temperatures, and to maternal protein nutritional levels when interpreting calf blood sera data. PMID- 1901850 TI - Lithium toxicity in an elderly woman. PMID- 1901849 TI - Effects of gaseous environment and temperature on the storage behaviour of Listeria monocytogenes on chicken breast meat. AB - Portions of skinless chicken breast meat (pH 5.8) were inoculated with a strain of Listeria monocytogenes and stored at 1, 6 or 15 degrees C in (1) aerobic conditions; (2) 30% CO2 + air; (3) 30% CO2 + N2; and (4) 100% CO2. When samples were held at 1 degree C the organism failed to grow under any of the test conditions, despite marked differences between treatments in spoilage rate and ultimate microflora. At 6 degrees C counts of L. monocytogenes increased ca 10 fold in aerobic conditions before spoilage of the meat, but only when the inoculum culture was incubated at 1 degree C rather than 37 degrees C. In CO2 atmospheres growth of L. monocytogenes was inhibited on meat held at 6 degrees C, especially under 100% CO2. By contrast, storage at 15 degrees C led to spoilage of the meat within 2 d, in all gaseous environments, and listeria levels increased up to 100-fold. Differences in the behaviour of L. monocytogenes on poultry and red meats are discussed. PMID- 1901851 TI - Crystallization and preliminary X-ray studies of a Bacillus subtilis and Thermus thermophilus HB8 chimeric 3-isopropylmalate dehydrogenase. AB - A chimeric gene was constructed by fusing the Bacillus subtilis and Thermus thermophilus genes coding for 3-isopropylmalate dehydrogenase, and expressed in Escherichia coli. The chimeric enzyme was crystallized in a size suitable for X ray structure analysis. The crystal has a space group of P3(1)21 or P3(2)21, a = b = 77.1 A and c = 158.3 A, which is isomorphous with that of the native enzyme from T. thermophilus. PMID- 1901852 TI - Direct interactions of mastoparan and compound 48/80 with GTP-binding proteins. AB - The effects of mastoparan and compound 48/80 on the activities of alpha beta gamma-trimeric GTP-binding proteins (G proteins) were studied with purified Go and Gi-1 which had been reconstituted into phospholipid vesicles. Pertussis toxin catalyzed ADP-ribosylation of Go or Gi-1 was inhibited by mastoparan or compound 48/80, suggesting that the G proteins were dissociated into their constituent alpha- and beta gamma-subunits in the presence of these compounds. The steady state rate of GTP hydrolysis catalyzed by Go or Gi-1 was stimulated by the two compounds. Both the stimulations were due to increases in the rate of the GDP-GTP exchange reaction occurring on the G proteins. However, the modes stimulation of the GTPase activity depended on the type of G protein used, and the stimulations caused by the two compounds were differently affected by pertussis toxin catalyzed ADP-ribosylation of G proteins. Moreover, the mastoparan-induced stimulation of the GTPase activity was partially inhibited by compound 48/80. Thus, the two histamine secretagogues mastoparan and compound 48/80 appear to activate G proteins differently, though they interact with the signal-transducing proteins, at least partly, at a common binding site. PMID- 1901853 TI - Kinetic studies on a novel sulfotransferase from Eubacterium A-44, a human intestinal bacterium. AB - A novel sulfotransferase purified from a human intestinal bacterium stoichiometrically catalyzed the transfer of a sulfate group of phenylsulfate esters to phenolic compounds. Vmax values of the enzyme reaction were measured with various concentrations of a sulfate donor substrate, p-nitrophenylsulfate, and of a sulfate acceptor substrate, tyramine. Double reciprocal plots of the acceptor concentration and Vmax showed a linear correlation. One of the reaction products, tyramine O-sulfate, competitively inhibited the enzyme as to a donor substrate, p-nitrophenylsulfate (PNS), but the other reaction product, p nitrophenol (PNP), noncompetitively inhibited it as to PNS. These kinetic data suggest that the sulfate transfer reaction proceeds according to a ping pong bi bi mechanism. The enzyme was activated by Mg2+ and inhibited by EDTA, which suggests that it is a metalloenzyme. PMID- 1901854 TI - Characterization of the half and overall reactions catalyzed by L-lysine:2 oxoglutarate 6-aminotransferase. AB - Significant differences were found in the reaction rate, and the substrate and reaction specificities between the half reactions and the overall reactions catalyzed by L-lysine: 2-oxoglutarate 6-aminotransferase. The half reactions between an amino donor and the enzyme-bound pyridoxal 5'-phosphate, and also between an amino acceptor and the bound pyridoxamine 5'-phosphate followed first order reaction kinetics. The extrapolated first order rate constants and dissociation constants of the substrates were determined for the half reactions: lysine, 0.87 min-1 and 5.5 mM; glutamate, 1.1 min-1 and 10.5 mM; alanine, 0.66 min-1 and 6.6 mM; 6-aminohexanoate, 0.43 min-1 and 13.3 mM; and 2-oxoglutarate, 0.33 min-1 and 2.5 mM. As compared with the values reported for the overall reactions [Soda, K., Misono, H., & Yamamoto, T. (1968) Biochemistry 7, 4102 4109], the reactivity of the inherent substrates was lower by over 4 orders in the half reaction than that in the overall reaction, and the reactivity of alanine with the bound pyridoxal 5'-phosphate was reduced to 10% of that in the overall reaction. The substrate specificity in the half reaction was much lower than that in the overall reaction, which was re-examined in a reaction system containing the same concentration of the enzyme as that for the half reactions. Lysine 6-aminotransferase catalyzes the transfer of only the terminal amino group of lysine to 2-oxoglutarate in the overall reaction. However, in the half reaction, the 2-amino group as well as the terminal one was transferred to the bound pyridoxal 5'-phosphate. The ratio of reactivity of the 2-amino group to that of the 6-amino group was considerably influenced by the pH of the reaction mixture.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1901855 TI - The epithelium, endothelium, and stroma of the rabbit cornea generate (12S) hydroxyeicosatetraenoic acid as the main lipoxygenase metabolite in response to injury. AB - Previous work has shown that, shortly after rabbit corneas are injured, arachidonic acid metabolism is activated, and 12-hydroxyeicosatetraenoic acid (12 HETE) is one of the main products formed (Bazan, H. E. P., Birkle, D. L., Beuerman, R., and Bazan, N. G. (1985) Invest. Ophthalmol. & Visual Sci. 26, 474 480; Bazan, H. E. P. (1987) Invest. Ophthalmol. Visual Sci. 28, 314-319). In order to determine whether this metabolite is a lipoxygenase product, anesthetized rabbit corneas injured in vivo, either cryogenically or by 1 M NaOH, were subsequently incubated in vitro with [14C] arachidonic acid in the presence of indomethacin. 12-HETE was the main metabolite produced, as established by gas chromatography-mass spectrometry. The (R)- and (S)-enantiomers of novel naphthoyl pentafluorobenzoyl derivatives of 12-HETE were resolved by chiral-phase high performance liquid chromatography. The radiolabeled 12-HETE from whole cornea and from isolated epithelium, endothelium, or stroma eluted as a single peak co chromatographing with the (S)-enantiomer and was detected both by UV absorbance at 234 nm and by radioactivity. In noninjured corneas a smaller peak of radiolabeled (12S)-HETE was also eluted from the chiral column. The stereochemistry was additionally confirmed by liquid chromatography-mass spectrometry. These studies suggest that (12S)-lipoxygenase is activated in the injured rabbit cornea. PMID- 1901856 TI - Transmembrane signal transduction and osmoregulation in Escherichia coli. Functional importance of the periplasmic domain of the membrane-located protein kinase, EnvZ. AB - The EnvZ protein is presumably a membrane-located osmotic sensor which is involved in expression of the ompF and ompC genes in Escherichia coli. Previously, we developed an in vitro method for analyzing the intact form of the EnvZ protein located in isolated cytoplasmic membranes, and demonstrated that this particular form of the EnvZ protein exhibits the ability not only as to OmpR phosphorylation but also OmpR dephosphorylation. In this study, to gain an insight into the structural and functional importance of the putative periplasmic domain of the EnvZ protein, a set of mutant EnvZ proteins, which lack various portions of the periplasmic domain, were characterized in terms of not only their in vivo osmoregulatory phenotypes but also in vitro EnvZ-OmpR phosphotransfer reactions. It was revealed that these deletion mutant EnvZ proteins are normally incorporated into the cytoplasmic membrane. Cells harboring these mutant EnvZ proteins showed a pleiotropic phenotype, namely, OmpF- Mal- LamB- PhoA-, and produced the OmpC protein constitutively irrespective of the medium osmolarity. It was also suggested that all of these mutant EnvZ proteins were defective in their in vitro OmpR dephosphorylation ability, while their OmpR phosphorylation ability remained unaffected. These results imply the functional importance of the periplasmic domain of the EnvZ protein for modulation of the kinase/phosphatase activity exhibited by the cytoplasmic domain in response to an environmental osmotic stimulus. PMID- 1901857 TI - Structure of the human aldose reductase gene. AB - The structure and sequence of the human gene for aldose reductase (AR) was determined by analysis of cDNA and genomic clones. The AR gene was independently isolated from two different cosmid libraries and the clones were characterized by restriction mapping, Southern blotting, and DNA sequencing. The gene extends over approximately 18 kilobases and consists of 10 exons giving rise to a 1,384 nucleotide mRNA (excluding the poly(A) tail). The human aldose reductase gene codes for a 316-amino acid protein with a molecular mass of 35,858 daltons. The size range for the exons is 82-168 base pairs (bp), whereas that for the introns is 325 to about 7,160 bp. A major site of transcription initiation in liver was mapped to an A residue 31 nucleotides upstream from the A of the ATG initiation codon. The promotor region of the gene contains a TATA (TATTTA) box and a CCAAT box which are located 37 and 104 nucleotides upstream, respectively, from the transcription initiation site. We have found four Alu elements in the AR gene; two are found in intron 1 and one each in intron 4 and intron 9. PMID- 1901858 TI - Cloning, expression, and sequence analysis of the genes for carbon monoxide dehydrogenase of Methanothrix soehngenii. AB - The cdhA and cdhB genes that code for the large and the small subunits of carbon monoxide dehydrogenase (CDH), respectively, were isolated from a genomic library of Methanothrix soehngenii DNA in Escherichia coli, using polyclonal antibodies raised against purified CDH. After introduction in E. coli or Desulfovibrio vulgaris, the cdh genes appeared to be expressed irrespective of their orientation, yielding immunoreactive proteins of 79 and 19 kDa, corresponding in size to the known subunits of purified CDH. However, no CDH activity could be detected in these heterologous hosts. The cdh genes are preceded by consensus ribosome-binding sites and are arranged in an operon-like structure, with cdhA preceding cdhB. Upstream from this operon, sequences similar to archaeal promoters were identified. The amino acid sequence, deduced from the primary sequence of cdhA, showed homology with ferredoxins and with acyl-CoA oxidase. This is compatible with the proposed functions of CDH. PMID- 1901859 TI - Characterization of an alpha 1----3-galactosyltransferase homologue on human chromosome 12 that is organized as a processed pseudogene. AB - UDP-Gal:Gal beta 1----4GlcNAc alpha 1----3-galactosyltransferase is a terminal glycosyltransferase that is widely expressed in a variety of mammalian species, with the notable exception of man, apes, and Old World monkeys. We recently reported the isolation of a bovine cDNA clone that contains the complete coding sequence for this enzyme (Joziasse, D. H., Shaper, J. H., Van den Eijnden, D. H., Van Tunen, A. J., and Shaper, N. L. (1989) J. Biol. Chem. 264, 14290-14297). Using this cDNA as a probe, we have demonstrated that, although transcripts cannot be detected in a variety of established human cell lines by Northern blot analysis, homologous sequences are present in human genomic DNA. To establish that these sequences represent a human homologue of alpha 1----3 galactosyltransferase, we have used the bovine cDNA as a probe to isolate two nonoverlapping clones (HGT-2 and HGT-10) from a human genomic DNA library. Clone HGT-2 contains a 1.5-kilobase uninterrupted linear sequence similar to bovine alpha 1----3-galactosyltransferase that is organized as a processed pseudogene. This sequence, flanked by Alu type repeats, contains a short 5'- and 3' untranslated region and a complete recognizable coding region that is 81% similar at the nucleotide level to bovine alpha 1----3-galactosyltransferase. This putative coding region contains multiple frameshift mutations and nonsense codons in all three reading frames which precludes the synthesis of a functional enzyme. Nevertheless, after optimal alignment, translation predicts a polypeptide that is 68% similar at the amino acid level to the bovine enzyme. Based on Southern analysis and limited sequence analysis, clone HGT-10 contains coding sequences similar to the NH2-terminal region of bovine alpha 1----3-galactosyltransferase. By analysis of panels of human-rodent somatic cell hybrids we have established that the nonfunctional, processed pseudogene and the human homologue represented by HGT-10 are located on human chromosomes 12 and 9, respectively. Interestingly, a comparison of the predicted amino acid sequence of the carboxyl-terminal two thirds of human alpha 1----3-galactosyltransferase, with the corresponding region of the human blood group A, UDP-GalNAc:[Fuc alpha 1----2]Gal beta 1----4GlcNAc alpha 1----3-GalNAc-transferase (Yamamoto, F., Marken, J., Tsuji, T., White, T., Clausen, H., and Hakomori, S. (1990a) J. Biol. Chem. 265, 1146-1151), reveals a significant similarity (39%) suggesting that these two enzymes may have arisen from the same ancestral gene as a result of gene duplication and subsequent divergence. PMID- 1901860 TI - Proteoglycans of bovine articular cartilage. The effects of divalent cations on the biochemical properties of link protein. AB - In cartilage proteoglycan aggregates, link protein stabilizes the binding of proteoglycan monomers to hyaluronate by binding simultaneously to hyaluronate and to the G1 globular domain of proteoglycan monomer core protein. Studies reported here involving metal chelate affinity chromatography demonstrate that link protein is a metalloprotein that binds Zn2+, Ni2+, and Co2+. Zn2+ and Ni2+ decrease the solubility of link protein and result in its precipitation. However, link protein is readily soluble and functional in low ionic strength solvents from which divalent cations have been removed with Chelex 100. These observations make it possible to study the biochemical properties of link protein in low ionic strength, physiologic solvents. Studies were carried out to define the oligomeric state of link protein alone in physiologic solvents, and the transformation in oligomeric state that occurs when link protein binds hyaluronate. Sedimentation equilibrium studies demonstrate that in 0.15 M NaCl, 5 mM EDTA, 50 mM Tris, pH 7, link protein exists as a monomer-hexamer equilibrium controlled by a formation constant of 2 x 10(27) M-5, yielding a delta G' of -36 kcal/mol for the formation of the hexamer from six monomers. On binding hyaluronate oligosaccharides (HA10 or HA12), link protein dissociates to dimer. Link protein hexamer is rendered insoluble by Zn2+. Greater than 90% of the protein is precipitated by 2 mol of Zn2+/mol of link protein monomer. The binding of hyaluronate oligosaccharide by link protein strongly inhibits the precipitation of link protein by Zn2+. The link protein/hyaluronate oligosaccharide complex is completely soluble in the presence of 2 mol of Zn2+/mol of link protein. At higher molar ratios of Zn2+/link protein, the inhibitory effect of hyaluronate oligosaccharide on the precipitation of link protein is gradually overcome. Hyaluronate oligosaccharide is not dissociated from link protein by Zn2+. Hyaluronate remains bound to the link protein which is precipitated by Zn2+, or to the link protein which binds to Zn2(+)-charged iminodiacetate-Sepharose columns. Hyaluronate oligosaccharides and Zn2+ bind to different sites on link protein. PMID- 1901861 TI - Inhibition of translational initiation by metalloendoprotease antagonists. Evidence for involvement of sequestered Ca2+ stores. AB - Synthetic oligopeptide inhibitors of metalloendoprotease activity have been shown to block membrane fusion events, to slow transport of secretory proteins from the endoplasmic reticulum (ER) to the Golgi, and to perturb Ca2+ homeostasis. Effects of such agents on translational activity, which requires Ca2+ sequestered putatively within the ER, were examined in this study. Cbz-Gly-Phe-NH2 (where Cbz is benzyloxycarbonyl) provoked rapid inhibition of amino acid incorporation into a broad spectrum of proteins in GH3 pituitary, C6 glial, and Neuro-2a cells but not in reticulocytes, which lack ER. Polysome accumulation and incorporation were reduced concurrently, indicating that the dipeptide acted to slow translational initiation. Inhibitions were largest at low extracellular Ca2+, were reversed by increasing extracellular Ca2+, were comparable to those achieved in the presence of EGTA or Ca2+ ionophores, and were observed with assorted metalloendoprotease antagonists but not with leupeptin. At concentrations inhibitory to protein synthesis Cbz-Gly-Phe-NH2 mobilized cell-associated 45Ca, lowered cytosolic free Ca2+, and did not generate inositol phosphates. Cells treated for 3-4 h with Cbz Gly-Phe-NH2 reacquired the ability to synthesize proteins at nearly normal rates; a phorbol ester or cAMP-elevating agent was necessary for such recovery in GH3, but not C6 or Neuro-2a, cells. GRP78, which may function in the folding and assembly of secretory proteins and in translational accommodation to agents that deplete sequestered Ca2+ stores, was induced during such treatments. Accumulation of GRP78 mRNA in treated preparations was reduced as extracellular Ca2+ was increased. Extended exposure to dipeptide followed by brief recovery in its absence rendered protein synthesis resistant to inhibition by Ca2+ ionophore. It is concluded that metalloendoprotease antagonists suppress translational initiation as a consequence of their capacity to mobilize sequestered Ca2+ stores. PMID- 1901862 TI - Interaction of purified actin-binding protein with the platelet membrane glycoprotein Ib-IX complex. AB - The interaction of platelet membrane glycoprotein (GP) Ib-IX complex with the cytoplasmic membrane skeleton is potentially of major importance in regulating platelet function. Indirect evidence suggested that this interaction is mediated by actin-binding protein, but it is not known whether GP Ib-IX and actin-binding protein associate directly. To examine more closely the nature of this association, purified GP Ib-IX complex was specifically bound and oriented on the surface of impermeable polymer beads via a monoclonal antibody, AK 2, directed against the extracytoplasmic domain of GP Ib alpha (glycocalicin). Binding was specific since 1) it was abolished by excess unlabeled actin-binding protein; 2) there was no detectable specific binding of radiolabeled actin-binding protein to beads coated with glycocalicin, the major extracytoplasmic proteolytic fragment of GP Ib alpha; and 3) unlike actin-binding protein, there was no specific binding of bovine serum albumin or human platelet vinculin to the GP Ib-IX complex-coated beads. Binding of actin-binding protein to the GP Ib-IX complex coated beads, but not to the glycocalicin-coated beads, was saturable and reversible (apparent Kd = 1 x 10(-7) M). These experiments provide direct evidence that actin-binding protein can bind to the cytoplasmic domain of a membrane glycoprotein. Because actin-binding protein is found submembranously in cells other than the platelet, it is possible that this protein may link actin filaments to the plasma membrane in those cells. PMID- 1901863 TI - Molecular cloning, characterization, and nucleotide sequence of the tagatose 6 phosphate pathway gene cluster of the lactose operon of Lactococcus lactis. AB - The tagatose 6-phosphate pathway gene cluster (lacABCD) encoding galactose-6 phosphate isomerase, tagatose-6-phosphate kinase, and tagatose-1,6-diphosphate aldolase of Lactococcus lactis subsp. lactis MG1820 has been characterized by cloning, nucleotide sequence analysis, and enzyme assays. Transcription studies showed that the four tagatose 6-phosphate pathway genes are the first genes of the lactose-inducible lactose-phosphotransferase operon consisting of the lacABCDFEGX genes. Using a T7 expression system, it could be shown that the lacA, lacB, lacC, and lacD genes code for proteins with apparent molecular masses of 15, 19, 33, and 36 kDa, respectively. Cell-free extracts of induced and noninduced Escherichia coli cells expressing the lacABCD genes were used to determine the functions of the encoded proteins. Expression of both lacA and lacB was required to obtain galactose-6-phosphate isomerase activity. The lacC gene codes for tagatose-6-phosphate kinase, the deduced amino sequence of which is similar to that of E. coli Pfk-2 phosphofructokinase, and Staphylococcus aureus LacC protein. The tagatose-1,6-diphosphate aldolase is encoded by the lacD gene, and its deduced primary sequence, which is homologous to that of the S. aureus LacD protein, predicts an amino acid composition which is virtually identical to that of the previously purified L. lactis E8 tagatose-1,6-diphosphate aldolase. PMID- 1901865 TI - The "anchor polypeptide" of cyanobacterial phycobilisomes. Molecular characterization of the Synechococcus sp. PCC 6301 apce gene. AB - In cyanobacteria, light energy is mainly harvested by the phycobiliproteins that form the phycobilisome rods, and funneled to the photosynthetic reaction centers through the core components. Among them, allophycocyanin (alpha AP, beta AP) and the so-called LCM play a major role. This report deals with the characterization of the apcE gene from Synechococcus sp. PCC 6301 which specifies the LCM. It maps upstream from the apcA gene (alpha AP). Transcriptional analyses demonstrate that the apcABC gene cluster (alpha AP, beta AP, and LC7.8) forms an operon, whereas the apcE gene behaves as a monocistronic unit. The functional organization of the apcEABC gene cluster, as well as of the apcE gene product, of Synechococcus 6301 are compared to their counterparts in three other organisms. Finally, a model is proposed for the architecture of the phycobilisome core. PMID- 1901864 TI - The adenine nucleotide-binding site on yeast 3-phosphoglycerate kinase. Affinity labeling of Lys-131 by pyridoxal 5'-diphospho-5'-adenosine. AB - The adenine nucleotide analog [3H]pyridoxal 5'-diphospho-5'-adenosine (PLP-AMP) is a potent and highly specific inactivator of yeast 3-phosphoglycerate kinase. Supportive evidence includes the finding that 1) during a 10-min incubation, half maximal inactivation is given by 10 microM PLP-AMP, 2) covalent incorporation of 1.2 mol of PLP-AMP/mol of enzyme is sufficient to give complete inactivation, and 3) MgATP gives near complete protection against modification and inactivation by PLP-AMP. Following reaction with PLP-AMP and reduction with NaBH4 to form a stable adduct, the enzyme was digested with endoproteinase Lys-C and peptides were separated by reversed-phase high-performance liquid chromatography. The single major labeled peptide was purified and sequenced, and the modified residue was identified as Lys-131. The crystal structure of enzyme in the open conformation shows Lys-131 to reside within a loop of flexible random coil positioned at the outer edge of the central binding cleft, approximately 2 nm from the surface of the cleft that comprises part of the MgATP-binding site (Watson, H. C., Walker, N. P. C., Shaw, P. J., Bryant, T. N., Wendell, P. L., Fothergill, L. A., Perkins, R. E., Conroy, S. C., Dobson, M. J., Tuite, M. F., Kingsman, A. J., and Kingsman, S. M. (1982) EMBO J. 1, 1635-1640). We conclude that the structural element containing Lys-131 undergoes substantial movement during the ligand-induced conformational change known to occur during formation of the ternary complex, resulting in the positioning of a basic residue near a negatively charged substrate. Since similar affinity-labeling results have been presented for hexokinase (Tamura, J. K., LaDine, J. R., and Cross, R. L. (1988) J. Biol. Chem. 263, 7907-7912), we further suggest that movement of positive charge into the central cleft may be a common step in the tight binding of nucleotides by bilobal kinases. PMID- 1901866 TI - Isolation of baculovirus-derived secreted and full-length beta-amyloid precursor protein. AB - We have expressed two forms of the Alzheimer's beta-amyloid precursor protein (beta APP), the 695-amino acid form (695 beta APP), and the 751-amino acid form (751 beta APP) in a baculovirus system. Both forms were expressed as full-length precursor, and were subsequently processed in vivo to release extracellular secreted proteins. The secreted forms were cleaved from the full-length beta APP in a manner analogous to the cleavage of beta APP during constitutive secretion in mammalian cells (Weidemann, A., Konig, G., Bunke, D., Fischer, P., Salbaum, J. M., Masters, C. L., Beyreuther, K. (1989) Cell 57, 115-126; Oltersdorf, T., Ward, P. J., Henriksson, T., Beattie, E. C., Neve, R., Lieberburg, I., and Fritz, L. J. (1990) J. Biol. Chem. 265, 4492-4497). High levels of expression of 20-50 mg/liter were achieved. Both full-length and secreted forms of the beta-amyloid precursor proteins were purified using a combination of ion-exchange and immunoaffinity chromatography using a monoclonal antibody directed against beta APP. The 751 beta APP-derived full-length and secreted forms, which contain the Kunitz protease inhibitor domain, were shown to be as active in the inhibition of trypsin as is mammalian-derived secreted beta APP. The availability of purified full-length beta APP from the baculovirus system will be valuable for biochemical and cell biological analyses that may elucidate the mechanism of the inappropriate processing that leads to beta-amyloid formation in Alzheimer's disease. PMID- 1901867 TI - Endocytosis and intracellular transport of the glycolipid-binding ligand Shiga toxin in polarized MDCK cells. AB - The glycolipid-binding cytotoxin produced by Shigella dysenteriae 1, Shiga toxin, binds to MDCK cells (strain 1) only after treatment with short-chain fatty acids like butyric acid or with the tumor promoter 12-O-tetradecanoylphorbol 13 acetate. The induced binding sites were found to be functional with respect to endocytosis and translocation of toxin to the cytosol. Glycolipids that bind Shiga toxin appeared at both the apical and the basolateral surface of polarized MDCK cells grown on filters, and Shiga toxin was found to be endocytosed from both sides of the cells. This was demonstrated by EM of cells incubated with Shiga-HRP and by subcellular fractionation of cells incubated with 125I-labeled Shiga toxin. The data indicated that toxin molecules are endocytosed from coated pits, and that some internalized Shiga toxin is transported to the Golgi apparatus. Fractionation of polarized cells incubated with 125I-Shiga toxin showed that the transport of toxin to the Golgi apparatus was equally efficient from both poles of the cells. After 1-h incubation at 37 degrees C approximately 10% of the internalized toxin was found in the Golgi fractions. The results thus suggest that glycolipids can be efficiently transported to the Golgi apparatus from both sides of polarized MDCK cell monolayers. PMID- 1901869 TI - Opioids and the prostanoid system in the control of cerebral blood flow in hypotensive piglets. AB - The interaction between opioid and prostanoid mechanisms in the control of cerebral hemodynamics was investigated in the conscious hypotensive piglet. Radiomicrospheres were used to determine regional cerebral blood flow (rCBF) in piglets pretreated with the opioid receptor antagonist, naloxone, or its vehicle, saline, during normotension, hypotension, and after the administration of indomethacin, a cyclooxygenase inhibitor, during hypotension. Hemorrhage (30 ml/kg) decreased systemic arterial pressure from 68 +/- 12 to 40 +/- 10 mm Hg but did not decrease blood flow to any brain region. Indomethacin treatment (5 mg/kg) of hypotensive piglets decreased blood flow to all brain regions within 20 min; this decrease in CBF resulted from increases in cerebral vascular resistance of 65 and 281% at 20 and 40 min after treatment, respectively. In hypotensive piglets, cerebral oxygen consumption was reduced from 2.62 +/- 0.71 to 0.53 +/- 0.27 ml 100 g-1 min-1 and to 0.11 +/- 0.04 ml 100 g-1 min-1 at 20 and 40 min following indomethacin, respectively. Treatment with naloxone (1 mg/kg) had no effect on rCBF, calculated cerebral vascular resistance, or cerebral oxygen consumption of normotensive or hypotensive piglets. However, decreases in CBF and oxygen consumption and increases in cerebral vascular resistance upon treatment of hypotensive piglets with indomethacin were attenuated in animals pretreated with naloxone. These data indicate that the removal of prostanoid modulation of an opioid-mediated constrictor influence on the cerebral circulation is a potential mechanism for the increase in cerebral vascular resistance that follows indomethacin treatment of hypotensive piglets. PMID- 1901870 TI - Isotachophoresis as an on-line concentration pretreatment technique in capillary electrophoresis. AB - One of the major disadvantages of capillary electrophoresis (CE) is its limited loadability. Therefore, the on-line coupling of isotachophoresis (ITP) and CE was studied with regard to its potential for the improvement of the minimum concentration that can be measured by CE. Based on the concentrating and separating power of ITP, detection limits could be lowered by at least two orders of magnitude. Especially for biological samples containing proteins, it appeared that in non-treated capillaries the electromigration characteristics are hardly influenced when isotachophoretic pretreatment is applied. The potential of ITP-CE coupling is illustrated by the analysis of o-phthaldialdehyde and fluorescein isothiocyanate derivatives of a number of amino acids. PMID- 1901868 TI - Laminin fragment E8 mediates PC12 cell neurite outgrowth by binding to cell surface beta 1,4 galactosyltransferase. AB - A number of cell surface receptors bind to distinct laminin domains, thereby mediating laminin's diverse biological activities. Cell surface beta 1,4 galactosyltransferase (GalTase) functions as one of these laminin receptors, facilitating mesenchymal cell migration and PC12 cell neurite outgrowth on laminin. In this study, the GalTase binding site within laminin was identified as the E8 fragment by assaying purified fragments and by immunoprecipitating and immunoblotting galactosylated laminin using E8-reactive antibodies. Compared with intact laminin and other laminin fragments, E8 possessed the highest GalTase binding activity, using both membrane-bound and solubilized GalTase. More significantly, the neurite-promoting activity of fragment E8 was shown to be dependent upon its interaction with GalTase. Pregalactosylating purified E8 eliminated subsequent GalTase binding and consequently inhibited neurite initiation; parallel studies on laminin fragments E1-4 or E1 failed to affect neurite outgrowth. Furthermore, anti-GalTase IgG inhibited neurite initiation on purified E8 substrates; control IgG had no effect. These results localize the predominant GalTase binding domain in laminin to fragment E8 and demonstrate that the neurite-promoting activity of E8 is dependent upon its interaction with GalTase. PMID- 1901871 TI - Ultrastructure of the ganglion cells of the terminal nerve in the dwarf gourami (Colisa lalia). AB - In our previous light microscopic studies (Oka et al., Brain Res. 367: 341-345, '86; Oka and Ichikawa, J. Comp. Neurol. 300: 511-522, '90), we reported that there are at least two types of terminal nerve (TN) cells based on cell size and immunoreactivity: type I cells had large cell bodies, while type II cells had smaller cell bodies. Type I TN cells were immunoreactive to gonadotropin releasing hormone (GnRH) and may be the major source of GnRH-immunoreactive fibers that are widely distributed throughout the brain. Type II TN cells, on the other hand, were not immunoreactive to GnRH. In the present paper, we examined the cytology and synaptology of these two types of TN cells with electron microscopy. Type I TN cell bodies were found to have morphological characteristics similar to those of other peptide-synthesizing neurons and are likely to be actively synthesizing GnRH. The frequent occurrence of coated vesicles close to the plasma membrane of the cell body was suggestive of membrane retrieval following exocytosis of the vesicular contents from the cell surface. Neighboring TN cells were either in direct juxtaposition with one another or made specialized "glomeruloid" cell-to-cell contacts; these specializations may be relevant for nonsynaptic intercellular communications among the TN cells. Within these glomeruloid complexes, the somatic processes of TN cells received inputs from two types of synaptic terminals: one containing only spherical synaptic vesicles and another containing a small number of dense-cored vesicles in addition to the spherical synaptic vesicles. Axosomatic synapses were rare on type I TN cell bodies. In contrast, type II TN cell bodies had morphological characteristics similar to those of neurons in other brain regions. These receive axosomatic inputs from synaptic terminals containing only spherical synaptic vesicles and those with a small number of dense-cored vesicles in addition to the spherical synaptic vesicles. Thus, each type of TN cell has unique fine structural characteristics which may correlate to their different functional roles. PMID- 1901872 TI - Marginal adaptation of Class V restorations using different restorative techniques. AB - This in vitro study compares the marginal adaptation of Class V restorations with margins located half in enamel and half in dentine, which were placed using different restorative techniques. Five operative procedures were evaluated both in saucer-shaped erosion lesions and in box-shaped cavities with bevels in enamel. The five procedures included a composite inlay technique using both the chemically and the light curing versions of a resin based composite cement, a bulk placement technique using a chemically curing composite resin, an incremental technique and an incremental technique combined with a built-up base, using a light curing composite resin. A combination of Gluma/Clearfil served as the dentinal adhesive. The micromorphology of the tooth/restoration interface was analysed before and after thermal cycling; the marginal seal was analysed after thermal cycling only. In the conventional cavities, the restorations showed less leakage, and micromorphologically a better, but statistically insignificant superior marginal adaptation. The inlay technique rendered the best marginal quality in both enamel and dentine before and after thermal cycling. Due to the unique curing characteristics of the chemically cured composite resin and cement resulting in a significantly reduced rigid contraction, the inlays cemented with the chemically curing cement and the restorations placed with the chemically curing composite resin were superior to their light cured counterparts. The built up base yielding a reduction of the composite mass did not enhance marginal adaptation because of the partial replacement of the strong adhesion to dentine mediated by the Gluma/Clearfil combination by the weaker bond promoted by the etched glass ionomer cement. PMID- 1901874 TI - Mentoring needs of dietitians: the mentoring self-management program model. AB - Twenty-one mentors and 24 mentees participated in a mentoring project in California. The results indicated that the mentoring needs among mentees were related to their career stage. Mentoring relationships were primarily serial rather than ongoing. Because of the present mercurial environment, individuals must plan much of their career development on their own. Recognition of the need for lifelong mentoring and knowledge of current findings can help dietitians move toward managing their own mentoring. We believe that the mentoring self management program model provides the flexibility and close personal contact dietitians need to develop their fullest professional potential. PMID- 1901875 TI - Cost justifying computerization of diet analysis. PMID- 1901873 TI - Identification, and susceptibility to seven antimicrobial agents, of 61 gram negative anaerobic rods from periodontal pockets. AB - Sixty-one cultures of Gram-negative anaerobic rods were isolated from deep periodontal pockets of patients with rapidly progressive periodontitis. Isolates were speciated as Bacteroides gingivalis (18 isolates), Bacteroides intermedius (8), Bacteroides oris (1), Bacteroides gracilis (17) and Fusobacterium nucleatum (17). Their susceptibilities, to seven antimicrobial agents, were determined in vitro using a plate dilution technique. Amoxycillin and amoxycillin with clavulanic acid were active against all isolates (MIC less than 1 mg/l) and proved the most effective agents tested. F. nucleatum and B. gracilis showed resistance to erythromycin; F. nucleatum had MIC values ranging from 0.03 mg/l up to 128 mg/l when tested with this, least effective agent. Metronidazole was effective against all isolates except for a few strains of B. gracilis (MIC less than 4 mg/l). Tetracycline hydrochloride and minocycline were active against all isolates except for a few strains of B. gracilis (MIC less than 2 mg/l with both minocycline and tetracycline hydrochloride). Penicillin proved less effective than amoxycillin with regard to inhibition of B. gracilis. PMID- 1901876 TI - Nosocomial transmission and infection control aspects of parasitic and ectoparasitic diseases. Part II. Blood and tissue parasites. PMID- 1901877 TI - Immobilization induces carbonic anhydrase III in type II fibers of rat skeletal muscle. AB - The amount and fiber distribution of carbonic anhydrase III (CA III), a major soluble protein in Type I muscle fibers, were studied during cast immobilization of rat hindlimb with the ankle in plantar or dorsiflexion. The concentration of CA III increased two- (p less than 0.05) and three- (p less than 0.01) fold in the shortened and lengthened tibialis anterior muscle during a 3-weeks immobilization period, respectively. After 6 weeks of immobilization the increase was even greater (p less than 0.001). Concomitantly, the number of CA III positive fibers in the lengthened muscle increased so that almost all fibers were positive. In the soleus muscle no significant change in the CA III concentration was seen. On the basis of actomyosin ATPase staining, the transition of Type IIb fibers towards Type IIa occurred in the tibialis anterior muscle, whereas in the soleus muscle a transformation of Type I fibers towards Type IIa fibers occurred. Therefore, the increase in the muscle CA III concentration seems to be associated with a cell transformation of the muscle towards a more oxidative type. PMID- 1901878 TI - Immunofluorescence analysis in flow cytometry: better selection of antibody labeled cells after fluorescence overcompensation in the red channel. AB - Selection of cells labeled with fluorescein isothiocyanate-conjugated (FITC) antibodies can be difficult if large autofluorescent cells are used and if the cells bind only a few molecules of antibody. We have developed a simple flow cytometric procedure that allows better selection of stained cells. When an argon ion laser emitting at 488 nm is used, the green fluorescence detected is the sum of cell autofluorescence and of the signal generated by the FITC antibody. Thus, when we subtract green signal from the red by fluorescence compensation, the signal of stained cells is on average reduced more than for the unstained counterpart. In this scenario, positive selection of cells with low red signal allows more efficient selection of stained cells. We tested the overcompensation procedure on mixtures of cells unstained and stained with a relevant FITC antibody. Cell mixtures were analyzed using normal vs increased levels of compensation in the red channel. Increased levels of compensation resulted in easier gating and higher recovery of stained cells. The efficiency of the overcompensation procedure was particularly high when using red filters with low cutoff (i.e., 560 or 570 nm), possibly because of the significant emission of fluorescein in the red channel, which caused separation between stained and unstained cells also in the red dimension. This method is useful for sorting cells expressing low levels of surface markers and facilitates selection of rare cells transfected with surface antigen genes. This technique is compatible with the use of propidium iodide for live/dead cell discrimination and with the subtraction of the cellular background of autofluorescence. PMID- 1901879 TI - Aspirin-like drugs prime human T cells. Modulation of intracellular calcium concentrations. AB - Aspirin-like drugs (ALD) enhance T cell proliferation by suppressing PG production in monocytes. Normal human T cells do not produce any eicosanoids. Therefore we studied whether ALD would affect purified T cells directly. We found that ALD enhanced the proliferation and IL-2 production of T cells in the absence of monocytes. This effect did not depend on arachidonic acid metabolism as no lipoxygenase products and only nonsuppressive levels of cyclooxygenase products were detected in T cell cultures. Several possible mechanisms of the ALD effect were ruled out including 1) enhanced mitogen binding, 2) induction of activation markers (IL-2R, transferrin receptor, HLA-DR) on the cell surface, 3) down regulation of suppressor cells. ALD caused a rise in [Ca2+]i which appeared to reflect an influx of Ca2+ from the extracellular milieu and was more pronounced in CD4+ cells. The rise in intracellular levels of Ca2+, that is considered a necessary second messenger for T cell activation, may prime these cells for an enhanced response to mitogens. In addition, ALD increased T cell membrane fluidity but only at higher concentrations than those found to enhance proliferation. The pharmacologic effect of ALD on T cells presents a possible new immunoenhancing potential of these drugs and may have therapeutic use in immunosuppressed individuals. PMID- 1901880 TI - Receptor-mediated elimination of phosphocholine-specific B cells in x-linked immune-deficient mice. AB - The combined expression of the M167 mu/kappa anstiphosphocholine (PC) transgenes with the x-linked immunodeficiency gene, xid, results in an almost total failure to develop B cells in the peripheral lymphoid organs of such mice. Although there is no significant difference between the normal transgene positive (TG+) female offspring and the immunodeficient TG+ xid males with respect to the number of B220+ pre-B cells and IgM+B220+B cells that develop in their bone marrow, the hemizygous xid males have 85% fewer B cells in their spleens than the phenotypically normal heterozygous F1 females. In xid M167-mu-transgenic mice, PC specific B cells also fail to develop in the spleen; however, numerous B cells bearing the mua+VH1(+)-transgene product associated with endogenous kappa L chains that do not give rise PC-specific antibodies are present. In the phenotypically normal TG+ (B6.CBA/N x mu 243-4)F1 female mice, PC-specific B cells represent almost 10% of the total B cell population, and these B cells express an M167-Id that has been produced by association of the VH1 transgene product with an endogenous V kappa 24L chain. B cells expressing the normally dominant T15-Id are not detectable in the spleens of these M167 mu-transgenic mice. Furthermore, M167-Id+ B cells are present at a fivefold lower level in the bone marrow of mu-TG+ normal mice than in their spleens. These data suggest that the PC-specific B cells that develop in TG+ xid mice are either clonally deleted via some "IgR-directed" mechanism or they fail to receive the appropriate signals to exit the bone marrow or to enter the peripheral lymphoid tissues. This hypothesis is supported by the finding that TNP-specific B cells develop normally and do not undergo clonal deletion in xid mice carrying the Sp6 mu/kappa anti-TNP transgenes. PMID- 1901882 TI - H chain C domains influence the strength of binding of IgG for streptococcal group A carbohydrate. AB - We have produced a panel of murine anti-streptococcal mAbs, expressing identical V domains and different H chain C domains, corresponding to the IgG3, IgG1, and IgG2b subclasses. We have used these mAb to evaluate the role of IgG subclass specific C region determinants in modulating the interaction between antibody and the bacterial surface. We report, for the first time, that V region-identical murine IgG of different subclasses exhibit substantial differences in binding to specific Ag; IgG3 mAb binds more strongly to streptococci than the IgG1 and IgG2b mAb or IgG3-derived F(ab')2 fragments. Furthermore, the IgG3 mAB binds cooperatively to the bacteria, whereas the IgG1, IgG2b, and IgG3-derived F(ab')2 fragments do not exhibit significant cooperativity, which suggests that differences in Fc region structure can affect antibody binding to multivalent Ag by modulating the potential for cooperative binding. These results suggest a plausible mechanism by which murine IgG3 could be more effective, than other antibodies bearing identical V domains, but of different gamma-subclass, in mediating bacterial immunity. PMID- 1901881 TI - Role of glycosaminoglycans in the regulation of T cell proliferation induced by thymic stroma-derived T cell growth factor. AB - The present study investigates the regulatory effects of glycosaminoglycans such as heparin and heparan sulfate on T cell proliferation induced by thymic stromal cell monolayer or its derived T cell growth factor (TCGF). A thymic stromal cell clone (MRL104.8a) supported the growth of Ag-specific, IL-2-dependent Th cell clone (9-16) in the absence of Ag and IL-2 by producing a unique TCGF designated as thymic stroma-derived T cell growth factor (TSTGF). The addition of heparin to cultures in which the growth of 9-16 Th cells was otherwise stimulated by the MRL104.8a monolayer or a semipurified sample of the TSTGF resulted in heparin dose-dependent inhibition of 9-16 Th proliferation. The dose of heparin required for inducing 50% reduction of TSTGF-induced proliferation of Th at a given cell number was found to be proportional to the magnitude of the TSTGF added to cultures, suggesting that heparin exerted its inhibitory effect by binding to the TSTGF rather than by acting on Th cells. A similar growth-inhibiting effect of heparin was observed in IL-7-dependent proliferation of pre-B cell line or Th, but not in IL-2-dependent T cell proliferation or IL-3-dependent myeloid cell proliferation. A strong affinity of TSTGF and IL-7 for heparin was confirmed by the fact that both TSTGF and IL-7 adhered to columns of heparin-agarose and were eluted by salt. When various glycosaminoglycans were tested for the heparin-like Th growth-regulatory capacity, heparan sulfate exhibited Th growth-inhibiting ability comparable to that observed for heparin. These results indicate that the activity of thymic and/or bone marrow stroma-derived lymphocyte growth factor (TSTGF/IL-7) but not of Th-producing TCGF (IL-2) is negatively regulated by heparin or heparan sulfate, which would represent major glycosaminoglycans in the extra-cellular matrix of stromal cells. PMID- 1901883 TI - Differential production of Th1- and Th2-derived cytokines does not determine the genetically controlled or vaccine-induced rate of cure in murine visceral leishmaniasis. AB - Recent studies with models of cutaneous leishmaniasis have provoked much interest in the role of CD4+ T cell subsets in determining the outcome of infectious disease. In Leishmania major infections, cure vs progressive disease correlates with the expansion of Th1-like or Th2-like CD4+ populations, respectively. We have investigated whether similar responses are associated with the differential patterns of infection seen in models of visceral leishmaniasis, caused by L. donovani. Splenic lymphocytes from infected Lsh congenic C57BL/10 (Lshs;H-2b) and B10.L-Lshr (Lshr;H-2b) mice and MHC congenic non-curing B10.D2/n (Lshs;H-2d) mice were examined for the production of cytokines representative of these CD4+ populations (IL-2, IL-3, IL-4, IL-5, and IFN-gamma). In all three strains examined, there was no evidence for the production of Th2-restricted cytokines. In addition, levels of serum IgE were depressed during the early phase of infection, indicative of in vivo IFN-gamma production. In the non-curing B10.D2/n strain, late phase of infection was associated with the decreased ability to produce cytokines in response to Ag and not with the production of IL-4 or IL-5 in response to Ag or mitogen. Serum IgE levels were also not raised above levels seen in uninfected controls. C57BL/10 mice were vaccinated with SDS-PAGE fractionated amastigote Ag bound to nitrocellulose and cytokine levels determined at various times after infection. The protocol used for vaccination was able to induce significant modulation of the course of infection in this strain and it was clear that IFN-gamma production in vitro provided an excellent correlate of rate of cure. Occasional individuals produced low levels of IL-5 in culture in response to parasite Ag, but this did not correlate with disease progression. Together, these data suggest that over-expansion of Th2-type cells and production of their specific cytokines (IL-4 and IL-5) is not a contributing factor to the variable long term course of L. donovani infection in these strains of mice. PMID- 1901884 TI - Differential T cell responses to Plasmodium chabaudi chabaudi in peripheral blood and spleens of C57BL/6 mice during infection. AB - The definition of the immune status of a person is often taken as the responses obtained from lymphocytes isolated from peripheral blood. We therefore analyzed in a mouse model of Plasmodium chabaudi chabaudi the response of T lymphocytes taken from peripheral blood and compared it with the spleen during and after a primary erythrocytic infection. Using limiting dilution conditions, no malaria specific T cell responses could be measured in the peripheral blood for up to 21 days after infection with P. chabaudi, whereas T cells responding to malaria Ag were readily detected in the spleen. This was true for T cells providing help and for those producing IFN-gamma. After clearance of the parasitemias to subpatent levels (75 days), qualitatively similar T cell responses were found in both compartments of the immune system, i.e., the Th cell response predominated over the inflammatory response. These data suggest that during an active infection with Plasmodium, T cell responses in peripheral blood are not necessarily indicators of the immune status. PMID- 1901885 TI - Mechanisms of host defense against Candida species. I. Phagocytosis by monocytes and monocyte-derived macrophages. AB - We studied the biochemical basis of phagocytosis of Candida albicans, a serious pathogen, and Candida parapsilosis, which is rarely pathogenic, by human monocytes (Mo) and monocyte-derived macrophages (MDM). Optimal phagocytosis of both species by Mo required the presence of extracellular Ca2+ and opsonization through both the classic and alternative complement pathways. Serum-opsonized Candida were ingested equally by Mo and MDM; unopsonized Candida were phagocytosed only by macrophages, and uptake began slowly. This opsonin independent phagocytosis required Ca2+ and could be blocked by yeast mannan or mannose-BSA conjugate, suggesting a role for the mannose receptor. Opsonized Candida elicited a vigorous increase in the concentration of [Ca2+]i in Mo and MDM, but no Ca2+ transient was detected in MDM stimulated with unopsonized Candida. Pretreatment of MDM with ionomycin to increase [Ca2+]i had no effect on phagocytosis of unopsonized Candida. Addition of 5 mM EGTA completely inhibited changes in [Ca2+]i in Mo and MDM, suggesting that the Ca2+ transient induced by opsonized Candida is due to an influx of extracellular Ca2+. Differences in pathogenicity between the two Candida species could not be explained by differences in any aspect of phagocytosis. Uptake mediated by the macrophage mannose receptor could play a role in clearance of Candida under opsonin-poor conditions. PMID- 1901886 TI - The human lambda L chain Ig locus. Recharacterization of JC lambda 6 and identification of a functional JC lambda 7. AB - The human lambda L chain Ig gene complex consists of multiple JC gene segments. A seventh human lambda C region gene segment, C lambda 7, was found 2.7 kb downstream of C lambda 6 in this gene complex. A J lambda gene segment, J lambda 7, was found 1.2 kb upstream of C lambda 7 and contains potentially functional nonamer and heptamer recombination sites, an RNA splice site and J coding region. C lambda 7 maintains an open reading frame and encodes a new lambda isotype. C lambda 7 encodes Kern+ and Oz- determinants, but does not encode any of the Kern+Oz- myeloma proteins published to date. Nevertheless, we present evidence that JC lambda 7 is transcribed in normal lymphocytes and is functional. In contrast, we present new data that the C lambda 6 gene segment, reported by others to encode the Kern+Oz- protein, is non-functional due to a 4-bp insertion in our cosmid clone. The 4-bp insertion was characterized further in 32 genomic DNA samples by producing a distinctive restriction fragment length and verified by the DNA sequences of the polymerase chain reaction products of two different cell lines. We discuss the possibility that the Kern+Oz- myeloma proteins do not define an isotype and are not encoded by JC lambda 7 nor other non-allelic genes, and we discuss the level of expression of JC lamba 7 as compared to that of JC lambda 2 and JC lambda 3. PMID- 1901887 TI - Factors affecting the rearrangement efficiency of an Ig test gene. AB - A rearrangement test gene, pHRD, containing the mouse IgH enhancer and the metallothionein promoter, has previously been shown to rearrange efficiently after transfection into a pre-B cell line. Experiments are now reported that assess the requirements of the DNA substrate as well as of the transfected cells for efficient rearrangement. It was found that deletion of the metallothionein promoter or substitution of the IgH enhancer by the kappa enhancer did not affect rearrangement. However, deletion of the Ig enhancer reduced the efficiency. Transfection of pHRD into stable hybrids of pre-B cells and myeloma cells resulted in a high frequency of rearrangement only if certain myeloma chromosomes were lost. Furthermore, pHRD introduced into rearrangement incompetent myeloma cells upon subsequent cell fusion with pre-B cells was rearranged only very rarely and then apparently only immediately after cell fusion. Stable pre-B cell x myeloma hybrids that retained the critical myeloma chromosomes were found to have lost VDJ recombinase activity and transcripts of the RAG-1, RAG-2 and TdT genes. It is concluded that transcription, i.e., the copying of the DNA by polymerase, is probably not required for rearrangement, but that the rearrangement substrate must be in an "open" chromatin state, such as may be provided by transcriptional factors. Furthermore, the absence of rearrangement in myeloma cells is apparently due to the continued action of an inhibitor of rearrangement. PMID- 1901888 TI - B cell abnormalities induced by a mu Ig transgene extend to L chain isotype usage. AB - We have analyzed the phenotype of B cell populations from mice transgenic for a rearranged Ig mu H chain gene. We find a decrease in the number of B cells in the spleens of these mice. Transgenic B cells have decreased surface levels of both IgM and IgD. The circulating IgM in these mice is 3- to 10-fold enriched in lambda L chains, compared with that in non-transgenic mice. Analysis of IgM producing hybridomas, from transgenic mice that express the transgene at high levels, demonstrates that this higher lambda frequency is observed in transgene nonexpressing as well as transgene-expressing hybridomas. A partial loss of L chain isotype exclusion is also noted in these hybridomas, and a significant proportion of primary B cells expressing both kappa and lambda L chains on their surface can be demonstrated. These findings suggest an ability of the transgenic Ig H chain to affect events in B cell ontogeny beyond the H chain locus. Our results support a quantitative model of exclusion for both the H chain alleles and the L chain isotypes. PMID- 1901889 TI - Characterization of syngeneic rat monoclonal antibodies to the HSN tumor using syngeneic monoclonal anti-idiotopic antibodies. AB - Twelve syngeneic anti-idiotopic mAb (anti-idiotypic/idiotopic antibodies Ab2)) were prepared from CBH/Cbi rats immunized with one of three monoclonal anti-HSN antibodies (Ab1) (11/160, ALN/11/53, or ALN/16/53) specific for the HSN tumor. The sera of the rats used for hybridoma production and all of the monoclonal Ab2 specifically inhibited the binding to HSN of the immunizing Ab1 only. It is concluded that, in this completely syngeneic system, only the private idiotopes associated with the antibody-combining site were immunogenic. Analyses using Western blotting showed that the Ab2 bound to intact Ab1 and to isolated H chains where the intra-strand disulfide bonds remained intact. The Ab2 did not bind to L chains or to fully reduced H chains of the Ab1. It is concluded that the idiotopes expressed on the H chain were conformational. When a panel of 13 monoclonal Ab1 (including the three used for immunization) were tested for reactivity with the Ab2, three reacted specifically with their respective Ab2 and 8 gave no binding suggesting that each Ab1 had a distinct idiotypic specificity despite the fact that all the Ab1 competed with each other for binding to Ag. However, the two remaining Ab1 (ALN/9/94 and ALN/12/17) generated from different tumor-bearing rats, were found to possess the same idiotypic specificity as 11/160. A detailed analysis using seven Ab2 raised against 11/160 showed that while the idiotype of ALN/9/94 and 11/160 were very similar, that of ALN/12/17 showed some clear differences. These three Ab1 have been shown previously to bind a sequential epitope on the HSN Ag in Western blots and it is postulated that the common idiotype of these Ab1 reflects their recognition of a sequential epitope. This may also account for the relatively frequent occurrence in tumor bearer sera of antibodies with this Id. PMID- 1901890 TI - Cholera toxin stimulates IL-1 production and enhances antigen presentation by macrophages in vitro. AB - Cholera toxin (CT) is a strong systemic and mucosal adjuvant that greatly enhances IgG and IgA immune responses. We investigated whether CT potentiates Ag presentation by macrophages as a possible mechanism underlying its adjuvant function. This was tested by preculturing APC in CT and analyzing the effect of CT treatment on the capacity to trigger 1) an allogeneic proliferative response of normal mesenteric lymph node T cells (H-2b) to the macrophage cell line P388D1 (H-2d) or 2) an Ag-specific proliferative response of D10.G4.1 clonal T cells in co-culture with normal macrophages and Ag. Pretreatment of APC, normal peritoneal macrophages or the P388D1 cells, with CT strongly enhanced Ag- and allogen specific T cell proliferation. Also P388D1 APC treated with CT and then formalin fixed demonstrated enhanced ability to stimulate T cell proliferation as compared to cells not exposed to CT, suggesting that the effect of CT on APC might be to enhance expression of a cell-associated factor. Flow microfluorimetry analysis of P388D1 cells cultured in CT-containing medium failed to detect an increase in class II MHC-Ag expression as compared to that found on cells not cultured in CT. In contrast, both soluble and cell-associated IL-1 formation was increased several-fold by CT, but with different CT dose requirements. A total of 10 to 100 times more CT were required for elevating the soluble IL-1 as compared to the cell associated IL-1, which was increased by as little as 1 ng/ml of CT. The soluble and cell-associated IL-1 activity induced by CT was abrogated by a polyclonal antiserum to IL-1-alpha. Similarly, the potentiating effect of CT on the ability of P388D1 APC to trigger alloreactive T cell proliferation was also blocked completely by the addition of the anti-IL-1-alpha antibody to the test system. This is the first study to demonstrate that CT potentiates Ag presentation. The mechanism for this effect probably involves induction of IL-1 production and in particular of a cell-associated form of IL-1 (IL-1-alpha). Potentiation of APC function might be important for the adjuvant action of CT on the immune response in vivo. PMID- 1901891 TI - Inducible expression of murine IP-10 mRNA varies with the state of macrophage inflammatory activity. AB - We have examined the expression of inducible inflammatory genes in murine macrophages from different tissues and at different stages of inflammatory activity. Although i.v. administration of IFN-gamma (10,000 U/mouse) strongly induced expression of IP-10 mRNA in the adherent cell population of the spleen, thioglycollate-elicited peritoneal macrophages were essentially unresponsive at the same dose. In contrast, D3 mRNA was expressed in both cell populations. This differential sensitivity of IP-10 mRNA expression was not restricted to stimulation by IFN-gamma as it was also seen when LPS (25 micrograms/mouse) was administered i.v. Expression of JE and KC mRNA, which encode cytokines related to IP-10, were also differentially expressed in elicited peritoneal macrophages from mice injected with LPS. Differential sensitivity was at least partially related to the state of macrophage activation because IP-10 mRNA was highly inducible in resident but not thioglycollate-elicited peritoneal macrophages. The eliciting agent was also an important determinant because proteose-peptone-elicited peritoneal macrophages were nearly as sensitive as splenic macrophages with respect to expression of IP-10 mRNA. IFN-gamma treatment induced IP-10 and D3 mRNA rapidly and transiently with the same time course in the spleen. IP-10 mRNA was not induced by IFN-gamma in TG-elicited macrophages regardless of the time after treatment. This differential expression of IP-10 was a consequence of different concentration requirements for IFN-gamma in the two cell types; thioglycollate-elicited macrophages required five- to 10-fold more IFN-gamma than did resident cells to achieve comparable IP-10 mRNA levels whether the agent was provided in vitro or in vivo. Thus variable sensitivity for induction of IP-10 mRNA was a characteristic of the macrophage itself and was not mediated by other cellular or molecular elements present in the inflammatory peritoneal cavity. The reduced sensitivity to IFN-gamma or LPS for expression of IP-10, JE, and KC mRNA as compared with TNF-alpha or D3 mRNA suggests that this distinct pattern of regulation may be restricted to members of these two related cytokine gene families that exhibit cell-type specific chemoattractant activity. PMID- 1901892 TI - Serologic and chemical differentiation of human lambda III light chain variable regions. AB - Human lambda L chains of a major V lambda subgroup, V lambda III, have been differentiated serologically and chemically into three V lambda III sub-subgroups designated V lambda IIIa, V lambda IIIb, and V lambda IIIc. Antisera prepared against lambda III Bence Jones proteins were obtained that recognized distinctive V lambda III-related epitopes expressed by monoclonal lambda III L chains. After appropriate absorption, these reagents were rendered specific for three distinct populations of lambda III proteins--lambda IIIa, lambda IIIb, and lambda IIIc. The antisera were used in comparative immunodiffusion analyses of 28 monoclonal lambda III L chains, 10 of which were classified as lambda IIIa, 4 as lambda IIIb, and 14 as lambda IIIc. The isotypic nature of the three lambda III sub subgroups was demonstrated serologically through analyses of lambda-chains derived from the serum IgG molecules of normal individuals. The amino acid sequences of five serologically classified lambda III chains, which included members of the three V lambda III sub-subgroups, had been previously determined. This information, in addition to our establishment of the complete (or virtually complete) V region sequence of 15 and the partial sequence of eight other lambda IIIa, lambda IIIb, and lambda IIIc proteins, made it possible to correlate chemical data with serologic classification. Proteins within each of the three serologically-classified lambda III sub-subgroups typically possessed a high degree (approximately 83%) of intra-sub-subgroup sequence homology that included both framework and complementarity determining region residues. Furthermore, within the framework and complementarity determining regions, sub-subgroup specific residues were identified. Taken together, these data reveal that the human V lambda III genome consists of (at least) three distinct V lambda IIIa, V lambda IIIb, and V lambda IIIc germline genes that encode for lambda IIIa, lambda IIIb, and lambda IIIc L chains, respectively. PMID- 1901893 TI - Bidirectional effects of cytokines on the growth of Mycobacterium avium within human monocytes. AB - Certain cytokines including IFN-gamma possess macrophage-activating factor activity that enhances the ability of these effector cells to destroy intracellular pathogens. A panel of recombinant and highly purified human cytokines was screened to detect this effect on the activation of human monocytes to kill Mycobacterium avium in an in vitro model. Peripheral blood monocytes obtained from 15 healthy donors were precultured for 2 days before infection. Monocytes were infected with two strains of M. avium, one AIDS-associated and relatively avirulent strain (86m2096), and the other a non-AIDS-associated isolate that demonstrated consistent and rapid growth in cultured human monocytes (LR114F). The effects of recombinant and purified human cytokines on M. avium infection were assayed by determining CFU of M. avium in lysates of infected monocytes after 0, 4, and 7 days of culture. After infection, monocytes were cultured in medium alone or continuously in the presence of the following cytokines: IL-1 alpha, IL-1 beta, IL-2, IL-3, IL-4, IL-6, IFN-gamma, granulocyte macrophage-CSF, or macrophage-CSF. In some experiments, cultures were performed in the presence of indomethacin (IM) in addition to cytokines. Culture in the presence of rIFN-gamma was associated with a decrease in mycobacterial growth within human monocytes. The combination of 300 U/ml of IFN-gamma plus 1 micrograms/ml of IM was associated with a 10-fold decrease (p less than 0.01) in intracellular growth of the virulent strain (LR114F) compared with unstimulated cultures. No other cytokine or combination of a cytokine with IM inhibited the intracellular growth of either strain of M. avium in human monocytes. Rather, several cytokines enhanced the intracellular growth of M. avium. IL-3, IL-6, and macrophage-CSF increased the growth of one, and IL-1 alpha of both strains of M. avium tested. IL-1 alpha and IL-6 also induced M. avium growth in tissue culture medium without monocytes. These studies indicate bidirectional effects of cytokines on intracellular parasitism that may influence the outcome of M. avium infection. PMID- 1901894 TI - Splenic macrophage function in early syphilitic infection is complex. Stimulation versus down-regulation. AB - Macrophages are important regulatory cells that can both stimulate and down regulate various immune functions. During syphilitic infection, these cells phagocytize, kill, and lyse Treponema pallidum. They also modulate early T cell activation by decreasing IL-2 production through secretion of PG. This report focuses on additional complexities of macrophage regulation. Non-adherent splenic cells were stimulated with Con A to induce IFN-gamma synthesis. High levels were detected in preparations from normal rabbits and much lower levels in preparations from infected rabbits. The organisms also readily stimulated IL-1 synthesis by adherent spleen preparations from normal but not from infected rabbits. When indomethacin was added to these latter preparations, this IL-1 defect was reversed, implicating PG in this down-regulation. Spleen cells were obtained from normal rabbits and from rabbits infected testicularly for 9 to 12 days. Infection elevated basal levels of class II Ia Ag on adherent cells. In addition, macrophage Ia expression was increased during 4 days of in vitro incubation with treponemes. Non-adherent spleen cells from infected animals inhibited two different macrophage functions. First, culture filtrates obtained after 48 h of incubation contained a soluble factor that subsequently decreased LPS-induced IL-1 synthesis. Second, when macrophages were co-incubated with non adherent cells, treponemal stimulation of macrophage Ia expression was inhibited; this inhibition was reversed by indomethacin implicating prostaglandins in this down-regulation. In further experiments an exogenous source of IFN-gamma was incubated with adherent cells from infected rabbits. This stimulated macrophage function as shown by increased IL-1 synthesis and Ia expression and decreased PGE2 secretion. Results are discussed in terms of the complexities of immunoregulation by macrophages during syphilitic infection. PMID- 1901896 TI - The E alpha promoter: a linker-scanning analysis. AB - To accurately delineate the DNA sequence elements involved in the transcriptional regulation of the murine MHC class II gene E alpha, we have constructed a set of "linker-scanning" mutants of the E alpha promoter region. These were made by the gapped heteroduplex technique and result in a set of 10-bp replacement mutations, covering the -206 to -6 stretch of the promoter. The effect of these mutations on transcriptional activity was evaluated in several systems, either by transfection into cultured cells or by in vitro transcription. The data points to the now classical X and Y boxes as the most important control elements, either for constitutive expression in B lymphoma cells, or for IFN-gamma-inducible expression in macrophages. Motifs upstream of the X box also play a role, but are somewhat less critical. Overall, we find no marked difference between regulatory strategies in B lymphomas or activated macrophages. PMID- 1901895 TI - Sequences homologous to class II MHC W, X, and Y elements mediate constitutive and IFN-gamma-induced expression of human class II-associated invariant chain gene. AB - Invariant chain (Ii) is intracellularly associated with MHC class II molecules, is implicated in class II function, and is coordinately regulated with the alpha- and beta-chains of MHC class II genes at the transcriptional level. Included among the various cis-acting elements of transcriptional control in MHC class II genes are the class II boxes, X and Y, and sequences 5' of X in the W (Z, H, S) region of class II genes. The Ii promoter region contains homologues of these elements, designated here as X, Y', and "W". This study utilized transient transfection and chloramphenicol acetyltransferase analysis to investigate the role of these elements in basal and inducible Ii gene expression. Invariant chain X, Y', and "W" all contribute to gene expression in B lymphoblastoid cell lines, making them likely candidates to mediate coordinate control of class II and Ii genes. IFN-gamma-inducible expression of the Ii gene in a glioblastoma cell line is also regulated through X, Y', and "W". Thus, the Ii class II boxes and "W" have dual roles in basal and inducible gene transcription. PMID- 1901897 TI - Somatic hypermutation of the JC intron is markedly reduced in unrearranged kappa and H alleles and is unevenly distributed in rearranged alleles. AB - Somatic hypermutation of the Ig genes occurs in rearranged V(D)J and its flanking sequences after Ag stimulation. Even though C regions and unrearranged V segments have been found to lack mutations, it is not known whether the mutational mechanism can be active in unrearranged J segments and their flanking regions. By polymerase chain reaction and direct sequencing of the 500 bp at the 5' end of the JC intron of hybridoma DNA derived from splenic B cells, we show that the frequency of mutations in unrearranged J regions of kappa and H chain genes is 0/7849 bp (upper 95% confidence interval, less than 0.00038) and 1/3209 bp (upper 95% confidence interval, less than 0.0015), respectively. The frequency (f) for the same region of rearranged kappa and H chain genes was 29/9380 bp (95% confidence, 0.0021 less than f less than 0.0044) and 16/2750 bp (95% confidence, 0.0033 less than f less than 0.0094), respectively. The significantly higher frequency of mutations in the rearranged alleles indicates that rearrangement is needed to effect full activation of the mutational mechanism. The data also show that mutations occur predominantly in the 5'-most 250 bp of the JC kappa intron. Statistical analysis of the distribution of mutations within the 5'-most 521 bp of the JC kappa intron reveals significant deviation (p = 0.000085) from a theoretically determined uniform distribution, indicating that mutations are not evenly distributed within this region. PMID- 1901898 TI - Evaluation of a spring-loaded syringe driver for the subcutaneous administration of narcotics. AB - A simple spring-loaded syringe driver was tested for the subcutaneous administration of narcotic analgesics and antiemetics. With concentrations of 2 to 10 mg/mL of hydromorphone and 10 to 50 mg/mL of morphine, the infusion rate during preclinical testing was 1.01 +/- 0.1 mL/hr (range 0.70-1.2 mL/hr). The rate of infusion was not modified by the concentration of narcotic in solution. Clinical trials were performed with morphine in 17 patients, and with hydromorphone in 11 patients. The duration of the infusion was 21 +/- 11 days. The most frequent reason for discontinuation was death (22 cases). The average duration of the site of infusion was 6.3 +/- 4 days. When used subcutaneously, the rate of infusion of the device was 1 +/- 0.15 mL/hr (range 0.70-1.30 mL/hr). Patients and nurses were satisfied with the simplicity and safety of the device. Cost analysis shows that this device is significantly less expensive than currently available portable infusion devices. We conclude that the Medifuse Pump is an inexpensive, safe and effective device for the subcutaneous infusion of narcotics and antiemetics. PMID- 1901900 TI - Pregnancy following sperm incubation in 2-deoxyadenosine (2-DXA) prior to in vitro fertilization (IVF). PMID- 1901899 TI - Timing of progesterone rise around a surge in endogenous luteinizing hormone or the injection of human chorionic gonadotropin in controlled ovarian stimulation for in vitro fertilization. PMID- 1901901 TI - Production and characterization of monoclonal antibodies to outer membrane proteins of Pseudomonas aeruginosa grown in iron-depleted media. AB - The iron uptake systems of pathogenic bacteria provide potential targets for immunological intervention. We have partially purified the high molecular mass, iron-regulated outer membrane proteins (IROMPs) from Pseudomonas aeruginosa and used them to prepare a panel of monoclonal antibodies (mAbs). Five mAbs reacted with an 85 kDa IROMP separated by SDS-PAGE, but gave only low-level binding to whole cells by immunogold electron microscopy. However, iodination of whole cells indicated that the 85 kDa IROMP is surface-exposed. The mAbs were only cross reactive with clinical isolates representing eight of the 17 International Antigenic Typing Scheme serotypes of P. aeruginosa, suggesting significant heterogeneity with respect to this IROMP. PMID- 1901902 TI - Purification and characterization of S layer proteins from Clostridium difficile GAI 0714. AB - The S layer of Clostridium difficile GAI0714 was shown to be composed of two proteins, of 32 kDa and 45 kDa, as determined by SDS-PAGE. The two proteins were extracted with 8 M-urea (pH 8.3) from a cell wall preparation and purified by DEAE-Sepharose CL-6B chromatography followed by HPLC gel filtration. When solubilized in 0.1 M-urea, both proteins appeared to exhibit dimeric forms, with respective molecular masses of about 61 kDa and 99 kDa, upon HPLC. Although the amino acid compositions of the two proteins differed from each other, both proteins had a high content of acidic amino acids, very low contents of histidine and methionine, and no cysteine. The 32 kDa protein exhibited multiple isoelectric forms (pI 3.7-3.9), whereas the 45 kDa protein had a single form (pI 3.3). Radioiodination and immunogold labelling revealed that both proteins were exposed evenly over the entire cell surface. Based on immunodiffusion analysis using monospecific antiserum raised to the individual proteins, there was no antigenic relationship between the two proteins. Furthermore, immunoblot analysis showed that the antigenicity of the 32 kDa protein appeared to be strain specific, whereas that of the 45 kDa protein appeared to be group specific. PMID- 1901903 TI - Cytolysis of Bacillus subtilis by Fusarium oxysporum. AB - Growth of Fusarium oxysporum on heat-killed Bacillus subtilis cells was accompanied by the loss of bacterial cytoplasmic contents, and this 'cytolysis' could be catalysed in heat-treated bacteria by the fungal culture fluids. In electron micrographs the bacterial walls appeared undamaged, and the absence of wall-lytic enzymes was confirmed by use of isolated bacterial walls as substrate. Appearance of cytolytic activity in cultures was paralleled by the production of proteolytic activity in the cultures. Proteolysis and cytolysis had similar pH optima at 8.8-9.0. Cultures grown on casein, but not glucose, produced high cytolytic activity. Rapid cytolysis occurred when heat-treated B. subtilis cells were incubated with trypsin, subtilisin or pronase E. Viable bacteria, however, were not attacked, either by concentrated culture fluids or by the commercial protease preparations. PMID- 1901904 TI - Analysis of the lacZ sequences from two Streptococcus thermophilus strains: comparison with the Escherichia coli and Lactobacillus bulgaricus beta galactosidase sequences. AB - The lacZ gene from Streptococcus thermophilus A054, a commercial yogurt strain, was cloned on a 7.2 kb PstI fragment in Escherichia coli and compared with the previously cloned lacZ gene from S. thermophilus ATCC 19258. Using the dideoxy chain termination method, the DNA sequences of both lacZ structural genes were determined and found to be 3071 bp in length. When the two sequences were more closely analysed, 21 nucleotide differences were detected, of which only nine resulted in amino acid changes in the proteins, the remainder occurring in wobble positions of the respective codons. Only three bases separated the termination codon for the lacS gene from the initiation codon for lacZ, suggesting that the lactose utilization genes are organized as an operon. The amino acid sequence of the beta-galactosidase, derived from the DNA sequence, corresponds to a protein with a molecular mass of 116860 Da. Comparison of the S. thermophilus amino acid sequences with those from Lactobacillus bulgaricus, E. coli and Klebsiella pneumoniae showed 48, 35 and 32.5% identity respectively. Although little sequence homology was observed at the DNA level, many regions conserved in the amino acid sequence were identified when the beta-galactosidase proteins from S. thermophilus, E. coli and L. bulgaricus were compared. PMID- 1901905 TI - Structural and stereospecific requirements for the nucleoside-triggered germination of Bacillus cereus spores. AB - A selection of adenosine analogues was tested for their ability to trigger germination of Bacillus cereus NCIB 8122 spores. The germination-inducing activity was governed by the structural properties of the sugar rather than the base moieties of the nucleosides. Among the sugar-modified analogues, only those containing a 2'-deoxy-D-ribose moiety promoted spore germination. Requirements for a specific molecular structure of the base were not clearly identified, although the highest activity was observed when substituents were inserted at position 6 of the purine ring. All the base-modified analogues, even those such as coformycin and 2'-deoxycoformycin with an expanded base ring, retained the germination-inducing activity of adenosine. However, of the two 2' deoxycoformycin diastereoisomers characterized by an asymmetric carbon atom at position 8 of the homopurine ring, only the 8S-isomer induced germination, thus indicating that stereospecific configuration of the inducer, at least in the case of 2'-deoxycoformycin, appears to be essential for the initiation of spore germination. The differences in the germination-inducing activity of the various analogues tested were not affected significantly by spore activation at different temperatures, although the higher the activation temperature, the lower was the concentration of each analogue required for maximum germination. PMID- 1901906 TI - Role of hepatocytes and Kupffer cells in age-dependent murine hepatitis caused by a phlebovirus, Punta Toro. AB - Punta Toro virus (PTV) infection of C57BL/6 mice results in fulminant hepatic necrosis and death in 3-week-old susceptible mice, but survival with minimal hepatocellular necrosis in 8-week-old resistant mice. Susceptibility in 3-week old mice is associated with an earlier rise of viral titers in liver and serum than that occurring in 8-week-old resistant mice. There is also an earlier and more rapid accumulation of infectious progeny in serum vs. liver after PTV infection in both age groups, suggesting that the virus may replicate in extrahepatic sites as well as the liver. PTV infection of isolated hepatocytes and Kupffer cells from 3- and 8-week-old mice demonstrates a significant age related difference in the ability of these cells to support replication of PTV in vitro (P less than 0.05). The age-related difference in liver cell-PTV interaction appears to be an inherent difference in the liver cells themselves, since there are no age-related differences in viral adsorption, morphogenesis, cytopathic effect, or interferon action within these cells. Thus, age-related differences in PTV replication or dissemination at extrahepatic sites, and the ability of the virus to replicate in intrahepatic sites, may be additive factors in the expression of age-related susceptibility to PTV in C57BL/6 mice. PMID- 1901907 TI - Identification of Hantavirus serotypes by testing of post-infection sera in immunofluorescence and enzyme-linked immunosorbent assays. AB - Serum samples were collected from 27 individuals who had been infected with a member of the genus Hantavirus in the Netherlands or Belgium during the last 15 years. These samples were tested in an immunofluorescence assay (IFA) and two enzyme-linked immunosorbent assay (ELISA) systems, using different virus strains that represented each of the four recently proposed serotypes of this genus. The serum samples from 11 individuals who had been infected through contacts with laboratory rats showed the highest reactivities with Hantaan virus (serotype I) and SR-11 (serotype II) in the IFA and ELISA systems. The samples of 16 individuals who had probably been infected through contacts with wild rodents showed the highest reactivities with Hallnas virus (serotype III) in the IFA. All except two of these also showed the highest reactivity with Hallnas virus in the two different ELISA systems. PMID- 1901908 TI - Human immunodeficiency virus-1 (HIV-1) in the vapors of surgical power instruments. AB - Cool vapors and aerosols produced by several common surgical power instruments and hot smoke plumes generated with electrocautery on known HIV-1 innoculated blood were gently bubbled through sterile viral culture media. Tissue culture cells were then added and cell infection was detected by the appearance of HIV-1 P-24 core antigen assayed by ELISA in the culture medium. HIV-1 was cultured from cool aerosols and vapors generated by a 30,000 RPM spinning router tip, an instrument similar to the Midas Rex and the Stryker oscillating bone saw. No infectious HIV-1 was detected in aerosols generated by a Valley Lab electrocautery or with a manual wound irrigation syringe known as a Travenol Uromatic irrigator. We have demonstrated that HIV-1 can remain viable in cool aerosols generated by certain surgical power tools and this raises the possibility of HIV transmission to medical personnel exposed to aerosols similarly generated during the care of HIV infected patients. Further work is required to determine whether such a risk exists but caution should be exercised by those exposed to aerosols generated during procedures on HIV-1 infected patients. PMID- 1901909 TI - Influence of hypobaric hypoxia in infancy on the subsequent development of vasoconstrictive pulmonary vascular disease in the Wistar albino rat. AB - A group of Wistar albino rats was injected subcutaneously with monocrotaline to induce vasoconstrictive hypertensive pulmonary vascular disease characterized by medial hypertrophy of small pulmonary arteries, the appearance of muscular pulmonary arterial vessels of arteriolar dimensions (less than 20 microns) in diameter), and exudative changes in the lung parenchyma. The vascular abnormalities were quantified by measuring the percentage medial thickness of small pulmonary arteries, the number of muscular pulmonary arterial vessels below 20 microns in diameter per cm2 of lung section and by determining the smallest arterial vessels in each case showing muscularity. A second group of rats was born in a decompression chamber and kept in hypobaric hypoxia for a month of the neonatal period, developing hypoxic hypertensive pulmonary vascular disease as a consequence. The animals in this group were allowed to recover in room air for a period of 3 months and were then injected with the same dose of monocrotaline as that given to the first group. The rats previously exposed to hypoxia exhibited an exaggerated response to the alkaloid, showing in particular many more small muscular pulmonary arterial vessels which were of a smaller diameter than those found in the eupoxic rats treated with the alkaloid. The experiment demonstrates the perinatal hypoxia exaggerates the effects of agents inducing vasoconstrictive pulmonary hypertension with a shift of the segment of the pulmonary arterial tree involved to the periphery as in hypoxia. Reports of a similar phenomenon are noted as occurring in babies born at high altitude, spending their infancy there and subsequently developing primary pulmonary hypertension later in life. PMID- 1901910 TI - New inhibitors of human renin that contain novel replacements at the P2 site. AB - A series of renin inhibitors with novel modifications at the P2 site has been prepared. Structure-activity relationships reveal that for a particular P2 fragment the in vitro potency is highly dependent on the nature of the P2' portion in addition to the P1-P1' group. The length of the P2 side chain and choice of epsilon-N P2 substitution have been found to be important for in vitro potency although the degree of unsaturation in the P2 side chain is not particularly significant. Molecular modeling studies have shown that it is possible for the P2 side chain to interact unfavorably with the P2' binding site. It has been possible to control the specificity for renin over cathepsin D by correct modification at the P2' and P1-P1' sites. Variations at the P4 site have been utilized to lower the log P values of these renin inhibitors while maintaining high potency. Compound 42, which exhibited an IC50 of 3.70 nM, log P of 2.3, and showed high specificity for renin, was selected for further studies. It was found to be very stable under neutral, acidic, and basic conditions. In simulated intestinal juice, compound 42 had a half-life of 37 min while it was virtually unaffected by simulated gastric juice after 4 h. Compound 42 produced a significant hypotensive response upon intravenous administration to the salt depleted normotensive cynomolgus monkey. PMID- 1901911 TI - Synthesis and evaluation of novel ether lipid nucleoside conjugates for anti-HIV 1 activity. AB - Combinations of an amidoalkylphosphocholine, 8, and AZT have been found to cause an apparent synergistic action in suppressing infectious HIV-1 replication. In addition, amidoalkyl, oxyalkyl, and thioalkyl ether lipids have been chemically linked to anti-HIV-1 nucleosides (AZT and DDI) through phosphate and phosphonate linkages. These conjugates have shown promising in vitro anti-HIV-1 activity. Also, the conjugates have a 5-10-fold reduction in cell cytotoxicity compared to AZT alone. The most active compound, an amidoalkyl ether lipid-AZT conjugates, 4A, was found to have a differential selectivity of 1793 in a syncytial plaque assay. In comparison, AZT alone has a value of 1281. PMID- 1901912 TI - Quinazolineacetic acids and related analogues as aldose reductase inhibitors. AB - A variety of 2,4-dioxoquinazolineacetic acids (10, 11) were synthesized as hybrids of the known aldose reductase inhibitors alrestatin (8), ICI-105,552 (9), and ICI-128,436 (2) and evaluated for their ability to inhibit partially purified bovine lens aldose reductase (in vitro) and their effectiveness to decrease galactitol accumulation in the 4-day galactosemic rat model (in vivo). In support to SAR studies, related analogues pyrimidinediones (12), dihydroquinazolones (13), and indazolidinones (14,15) were synthesized and tested in the in vitro and in vivo assays. All prepared compounds (10-15) have shown a high level of in vitro activity (IC50 approximately 10(-6) to 4 x 10(-8) M). However, only the 2,4 quinazolinedione analogues 10 and 11, with similar N-aralkyl substitution found in 2 and 9, have exhibited good oral potency. The remaining compounds were either inactive or had only a marginal in vivo activity. The structure-activity data support the presence of a secondary hydrophobic pocket in the vicinity of the primary lipophilic region of the enzyme. PMID- 1901913 TI - Immunocytochemical localization of apolipoprotein A-I using polyclonal antibodies raised against the formaldehyde-modified antigen. AB - The preparation of cells for electron microscopy, in particular the fixation and embedding routine, influences the antigenicity, often resulting in a markedly reduced labelling intensity. To overcome the difficulties associated with fixation-induced changes in antigenicity, we produced antibodies against pre fixed human apolipoprotein (apo) A-I. Purified apo A-I was fixed with 4% formaldehyde and was used to raise polyclonal antibodies in rabbits. The antiserum was purified by protein-A-Sepharose followed by affinity chromatography with the fixed antigen coupled to vinylsulphone-activated agarose. The specificity of the antibodies was ascertained by enzyme-linked immunosorbent assay (ELISA) and Western blot analysis against different fixed and unfixed lipoproteins. In ELISA, the reaction of the antibodies was markedly enhanced with the fixed antigen, indicating that the antibodies were directed against epitopes characteristically modified by the fixation. The efficacy of the antibodies for light and electron microscopy was tested on HepG2 cells and on human liver cells. When HepG2 cells were exposed to anti-apo A-I antibodies followed by a secondary FITC-labelled antibody, fluorescence was found intracellularly in distinct regions. Electron microscopy revealed that the endoplasmic reticulum, and in particular the trans elements of the Golgi complexes, were the main compartments stained for apo A-I both in HepG2 cells, as shown by the immunoperoxidase technique, and in human hepatocytes, as shown by the protein-A-gold technique on ultrathin cryosections. The findings demonstrate the potential of using antibodies to fixed antigens as a strategy to overcome impaired localization due to fixation in cytochemistry at the light microscopic and electron microscopic levels. PMID- 1901914 TI - The observed form of coated vesicles and a mathematical covering problem. AB - A connection is made between (1) the observed structures of clathrin cages and (2) the mathematical problem of determination of the smallest diameter of n equal circles by which the surface of a sphere can be covered without gaps. For different numbers n of circles, it is found that the various clathrin polyhedra identified so far provide topologically the same configurations as the proven solutions of the sphere-covering problem for some n or improve on the currently best conjectured solutions for other n. Thus a study of some biological structures has, in this case, given additional insight into a mathematical problem. PMID- 1901915 TI - Human immunodeficiency virus (HIV)-infected tumor xenografts as an in vivo model for antiviral therapy: role of alpha/beta interferon in restriction of tumor growth in nude mice injected with HIV-infected U937 tumor cells. AB - The host factors involved in the restriction of tumor growth were studied in nude mice transplanted with a cloned line of chronically human immunodeficiency virus (HIV)-infected U937 cells. HIV-infected and uninfected U937 cells exhibited the same growth patterns in culture. However, HIV-infected cells were not tumorigenic when injected subcutaneously in nude mice, whereas large solid tumors were observed in mice injected with uninfected U937 cells. Injection of nude mice with antibody to alpha/beta interferon (IFN-alpha/beta) enabled HIV-infected U937 cells to grow progressively in approximately 90 to 100% of mice. HIV-infected U937 cells formed solid tumors in the majority (60 to 90%) of either immunosuppressed (splenectomized, irradiated, and anti-asialo-GM1-treated) or genetically immunodeficient (bg/nu/xid) nude mice. In mice treated with antibodies to IFN-alpha/beta with established HIV-positive tumors, a direct correlation was found between p24 antigenemia and tumor size. Treatment of established HIV-positive U937 cell tumors with human IFN-alpha or mouse IFN alpha/beta resulted in a clear-cut inhibition of both tumor growth and p24 HIV antigenemia. In contrast, treatment with tumor necrosis factor alpha markedly inhibited tumor growth but did not significantly decrease serum p24 levels. 3' Azido-3'-deoxythymidine treatment did not affect either tumor growth or the levels of serum p24 antigen. These data indicate that endogenous IFN-alpha/beta is a crucial factor in the restriction of both tumor growth and p24 antigenemia in mice injected with HIV-infected tumor cells. Moreover, the results suggest that the development of HIV-1 p24 antigenemia in athymic immunosuppressed mice may represent an interesting in vivo model for anti-HIV therapy. PMID- 1901917 TI - Assembly of empty capsids by using baculovirus recombinants expressing human parvovirus B19 structural proteins. AB - Empty parvovirus B19 capsids were isolated from insect cells infected with a recombinant baculovirus expressing parvovirus B19 VP2 alone and also with a double-recombinant baculovirus expressing both VP1 and VP2. That VP2 alone can assemble to form capsids is a phenomenon not previously observed in parvoviruses. The stoichiometry of the capsids containing both VP1 and VP2 was similar to that previously observed in parvovirus B19-infected cells. The capsids were similar to native capsids in size and appearance, and their antigenicity was demonstrated by immunoprecipitation and enzyme-linked immunosorbent assay with B19-specific antibodies. PMID- 1901918 TI - The effect of intravesical instillations of thiotepa, mitomycin C, and adriamycin on normal urothelium: an experimental study in rats. AB - The effects of intravesical instillations of thiotepa, mitomycin C and adriamycin on the normal urothelium were studied in rats. Changes in the bladder wall in the form of fibroblastic atypia and submucous fibrous plaques were significant in the mitomycin C treated group. In 46% of mitomycin C treated animals there was urothelial atypia and in one animal, the atypia was severe enough to resemble carcinoma in situ. None of the rats treated with thiotepa showed intramural fibrous plaques or fibroblastic atypia and only 8% showed urothelial atypia. In the group treated by adriamycin instillation, 17% showed intramural fibrous plaques, but none showed urothelial atypia or fibroblastic atypia. The fibroblastic atypia and submucosal fibrous plaques seen in the mitomycin treated group may explain the reduced bladder capacity seen in the clinical setting. PMID- 1901916 TI - Site-specific mutagenesis identifies three cysteine residues in the cytoplasmic tail as acylation sites of influenza virus hemagglutinin. AB - The hemagglutinin (HA) of influenza virus is a type I transmembrane glycoprotein which is acylated with long-chain fatty acids. In this study we have used oligonucleotide-directed mutagenesis of cloned cDNA and a simian virus 40 expression system to determine the fatty acid binding site in HA and to examine possible functions of covalently linked fatty acids. The results show that the HA is acylated through thioester linkages at three highly conserved cysteine residues located in the cytoplasmic domain and at the carboxy-terminal end of the transmembrane region, whereas a cysteine located in the middle of the membrane spanning domain is not acylated. Mutants lacking fatty acids at individual or all three attachment sites acquire endoglycosidase H-resistant oligosaccharide side chains, are cleaved into HA1 and HA2 subunits, and are transported to the plasma membrane at rates similar to that of wild-type HA. All mutants are membrane bound and not secreted into the medium. These results exclude transport signal and membrane-anchoring functions of covalently linked fatty acids for this integral membrane glycoprotein. Furthermore, lack of acylation has no obvious influence on the biological activities of HA: cells expressing fatty acid-free HA bind to and, after brief exposure to mildly acidic pH, fuse with erythrocytes; the HA-induced polykaryon formation is not impaired, either. Other possible functions of covalently linked fatty acids in integral membrane glycoproteins which cannot be examined in conventional cDNA expression systems are discussed. PMID- 1901919 TI - The effects of recombinant human interferon-gamma on a panel of human bladder cancer cell lines. AB - We have examined the Major Histocompatibility Complex class II antigen inducing capabilities of recombinant human interferon-gamma, on a panel of human transitional cell carcinoma lines which have been raised from original tumours of varying histological grades: RT4 (grade 1), RT112 (grade 2) and MGH-U1 (grade 3). Cells were examined for class II antigens using an indirect immunofluorescent staining method and analysed on a fluorescence activated cell sorter. Twenty percent of RT4 cells constitutively expressed class II antigen. Both RT112 and MGH-U1 were repeatedly found to be negative for this antigen prior to treatment with interferon-gamma. Following treatment with interferon-gamma all three lines showed an increase in class II antigen expression, which was consistently dependent on both the length of incubation and concentration of interferon-gamma. A differential susceptibility was found amongst the three cell lines which may relate to the histological grade of the parent tumor. PMID- 1901920 TI - Prognostic significance of T cell associated surface antigen density changes during OKT3 therapy of renal allograft rejection. AB - We describe 12 acute rejection episodes in 11 cadaver donor renal allograft recipients who required OKT3* rescue treatment for steroid-resistant acute rejection (9) or for severe vascular (antibody-mediated) rejection (3). There were 3 treatment failures with subsequent graft loss. Using 2-color flow cytometry the total T (CD3), B (DR+), activated T (CD3DR), T helper/inducer (CD4), T cytotoxic/suppressor (CD8) and activated T cytotoxic cell (CD8DR) subsets were analyzed before, in mid course (5 to 7 days) and at the end of 12 to 14 days of therapy with 5 mg. OKT3 intravenously daily. In parallel changes in the density of such T cell associated antigens were analyzed. Significant decreases in the mean levels of the CD3 (p less than 0.001), CD3DR (p less than 0.05), CD4 (p less than 0.05), CD8 (p less than 0.05) and CD8DR (p less than 0.05) subsets were observed at mid course. A significant decrease in the density of CD3 was observed (p less than 0.0001). The surface antigen density of CD3DR, CD4 and CD8 had decreased by 160% (p less than 0.002), 383% (p less than 0.001) and 260% (p less than 0.001), respectively. At the end of treatment CD3 and CD4 subset levels increased by 425% and 240% (p less than 0.001 and p less than 0.005), respectively. In contrast, the CD3DR and CD8DR subset levels continued to decrease (p less than 0.05). A higher pre-treatment level of CD3DR and a less sharp decrease in CD3, CD4 and CD8 subsets were associated with a higher risk of treatment failure (p less than 0.05, p less than 0.01, p less than 0.05 and p less than 0.05, respectively). The mean decrease in the density of the CD3 marker in the lost grafts was significantly smaller compared to successful outcomes (p less than 0.001). The results of this preliminary study suggest that OKT3 affects T cell associated antigens other than CD3. Such may provide a sensitive prognostic index for the effectiveness of OKT3 therapy, and permit the identification of those patients who might require higher doses and/or duration of OKT3 therapy to enhance renal allograft salvage rates. PMID- 1901921 TI - How well has Canada contained the costs of doctoring? AB - Canada's provinces have had varying success at containing the costs of physician services through the use of fee schedules and expenditure targets. This article examines the wide variation in the increases in the costs of physician services among Ontario, Quebec, and British Columbia between 1975 and 1987. Cost increases during that time resulted from various combinations of increases in prices (fees) and utilization, stimulated by an increased supply of physicians. Differences among the three provinces resulted from differences in the aggressiveness of fee schedule controls and whether expenditure targets were imposed. Regardless of the degree of expenditure increases, utilization increased steadily in all three provinces and was associated most consistently with growth in the supply of physicians. This was most dramatically illustrated in Quebec, which noted the most rapid rise in physician-to-population ratio. Cost containment may ultimately require constraints on the number of new physicians in addition to controls on fees and utilization. PMID- 1901922 TI - How many physicians can we afford? AB - We project physician costs for the year 2,000 under several alternative scenarios, using different assumptions about the future supply of physicians and gross income (or expenditures) per physician. The supply of active, posttraining patient-care physicians is projected to increase from a ratio of 144 per 100,000 population in 1986 to 176 per 100,000 in 2,000. Depending on whether expenditures per physician increase at the rate of the consumer price index, the gross national product, or the historical 1982 through 1987 expenditure trends, there will be an additional cost (in constant 1986 dollars) of $21 billion, $30 billion, or $40 billion, respectively, compared with projected physician costs under a scenario of a constant physician-to-population ratio. The disproportionate growth of costs for practice overhead will pose a particular problem for efforts to restrain inflation of expenditures per physician. PMID- 1901923 TI - Expansion of health care to the uninsured and underinsured has to be cost neutral. AB - Any attempt to address the problem of more than 30 million uninsured and 25 million seriously underinsured citizens in the United States has to be able to offer medical services to this 20% of the population in a cost-neutral way for the US economy, since present economic conditions do not permit further expansion in health care costs. A medical system compartmentalized by medical specialty should be able to save approximately 20% of present-day health care expenditures within each specialty, which then can be used to provide the necessary coverage. Some suggestions are made as to how such cost savings can be achieved. Only an effort spearheaded by physicians can achieve the outlined targets, since, otherwise, physician efforts will easily subvert such attempts. A physician initiative that could solve the crisis would reestablish physicians as leaders in determining national health care policy and should consequently improve the recently disappointing societal image of the profession. PMID- 1901924 TI - Controlling medical care costs in Canada. PMID- 1901925 TI - Serum levels of glucose, insulin, and C-peptide during long-term D-ribose administration in man. AB - D-ribose was given orally and/or intravenously to nine healthy subjects at doses ranging from 83.3 to 222.2 mg/kg per hour for at least four hours. The serum ribose level increased in a dose-dependent manner to maximum concentrations of 75 to 85 mg/dl. The serum glucose level decreased after the beginning of continuous ribose administration and was reduced as long as ribose was being administered. The oral or intravenous administration of 166.7 mg/kg per hour of ribose resulted in a 25% decrease in serum glucose. Higher intravenous doses of ribose did not provoke a further decrease in serum glucose concentration. Oral administration of 166.7 mg/kg per hour led to an increase in serum insulin concentrations from a mean of 8.4 (range 6.4-11.5) to 10.4 (range 6.3-15.4) microU/ml (p less than 0.05). In contrast, intravenous administration did not change serum insulin concentrations significantly. The serum c-peptide concentration remained unchanged regardless of treatment. We conclude that the variations in plasma insulin concentrations do not account for the observed decrease in mean serum glucose concentrations accompanying D-ribose administration. PMID- 1901926 TI - Spectrum of glomerular and tubulointerstitial renal lesions associated with monotypical immunoglobulin light chain deposition. AB - The purpose of this study was to characterize the spectrum of renal lesions associated with plasma cell dyscrasias from a population of patients who had renal disease identified by kidney biopsy. Thirty-six patients (2.6% of 1361 kidney specimens examined over 6 years) had evidence of monotypical light chain with or without concomitant heavy chain deposition. A variety of lesions was found, including (a) AL-amyloid and glomerular nonamyloid light chain deposition manifesting as nodular, membranoproliferative, mesangioproliferative, and "minimal-change" glomerulopathies; (b) fibrillary glomerulopathy; (c) tubulointerstitial lesions (cast nephropathy, acute tubular necrosis, and tubulointerstitial nephritis); and (d) vascular (arterioles and small and medium sized arteries) lesions. AL-amyloid was the most common renal lesion (39%), nonamyloid deposition occurred second most commonly (33%), and cast nephropathy ("myeloma kidney") was third most frequent (14%). Clinical and laboratory manifestations of a plasma cell dyscrasia were frequently subtle. Immunoelectrophoresis of both serum and urine did not demonstrate a monotypical light chain or immunoglobulin in almost 35% of this population. Thus, the correct diagnosis was not considered in the majority of these patients before biopsy. Progressive deterioration of renal function was common with all of the lesions, except for proximal tubule injury, which tended to improve over the period of study. Renal biopsy with careful examination for monotypical light chain with or without associated heavy chain deposition using immunofluorescence or immunoelectron microscopy was crucial in identifying and characterizing the varied lesions associated with lymphoplasmacytic disorders. PMID- 1901927 TI - Histogenesis and differentiation potential of central neurocytomas. AB - The central neurocytoma, a recently identified rare supratentorial brain tumor in young adults, is characterized by intraventricular location and a usually benign clinical course. In order to elucidate the histogenesis and differentiation potential of this neoplasm, we have undertaken an immunocytochemical and molecular biological study of four central neurocytomas. It was found by immunocytochemistry and immunoblotting that all tumors express neuron-specific enolase and synaptophysin. Western blots also revealed expression of the synaptic vesicle protein, synapsin I, neurofilament protein and glial fibrillary acidic protein in several neurocytomas which failed to exhibit immunoreactivity to these marker antigens on paraffin sections. Immunocytochemical reactions with antibodies to synaptophysin and glial fibrillary acidic protein on adjacent sections demonstrated coexpression in individual tumor cells. The neuronal form of the pp60src protein-tyrosine kinase, an oncogene-product specifically expressed in central nervous system neurons, was not detectable in two central neurocytomas investigated. N-myc, a proto-oncogene frequently amplified in childhood neuroblastomas, was present as a single copy gene in all central neurocytomas, indicating that amplification of this gene is not involved in the pathogenesis of the central neurocytoma. In accordance with ultrastructural evidence of synaptogenesis, we conclude that the central neurocytoma is a neuroectodermal tumor with consistent commitment for neuronal differentiation. Since these tumors retain a potential for additional glial differentiation, we propose an origin from bipotential progenitor cells in the periventricular matrix, which in the mammalian brain persists throughout adult life. PMID- 1901929 TI - [Centralized compounding of cytostatics results in better service and lower cost]. PMID- 1901930 TI - [Chronic hepatitis: current diagnostics and treatment in different etiologic factors]. PMID- 1901928 TI - Tumor necrosis factor in the cerebrospinal fluid of children with central nervous system leukemia. AB - To clarify the role of cytokines in cerebrospinal fluid (CSF) in the pathogenesis of central nervous system (CNS) leukemia, three cytokine activities, interleukin 1 (IL-1)-beta, tumor necrosis factor (TNF)-alpha, and interferon (IFN)-gamma, and their correlations with other laboratory studies of the CSF were analysed in 23 children with acute leukemia. These patients were classified into three groups: group A (n = 8)--patients with overt CNS leukemia, group B (n = 5)--patients with CNS leukemia in remission, group C (n = 10)--patients without CNS disease. IFN gamma in the CSF was undetectable in these 23 patients. There was no difference in IL-1-beta levels among the three groups. However, TNF-alpha levels were significantly higher in group A than in group B, and higher in group B than in group C. By Kendall's rank sum test, high TNF levels in CSF correlated with high CSF leukemic cell counts and low sugar levels. In two patients with overt CNS leukemia, the TNF level in the CSF decreased gradually with intrathecal chemotherapy. These results indicate that TNF released from stimulated cells in the cerebrospinal space may induce CNS leukemia-related symptoms or alter laboratory parameters measured in the CSF. TNF levels in CSF may also prove useful in diagnosing early CNS involvement in children with acute leukemia. PMID- 1901931 TI - Inhibition of cell proliferation by glycerol. AB - The effect of glycerol on proliferation of BHK, CHO, HBL, MCF-7, and human glioma cells was studied. Cell proliferation was significantly decreased in all the cell lines at glycerol concentrations of 2-4% in the culture medium. The inhibition was dose-dependent, complete suppression of proliferation occurring at a glycerol concentration of 4% for the MCF-7 cell line and 6-8% for the BHK, CHO and human glioma cells. Studies on [3H]thymidine incorporation correlate with the effect on cell proliferation. The viability of the cells was not significantly affected until higher concentrations of glycerol (12% +) were present. Recovery studies with BHK cells indicated that replacement of the glycerol medium with glycerol free medium resulted in full recovery following exposure to 4% glycerol and only partial recovery (65%) of proliferation rate following exposure to 10-12% glycerol. It is concluded that glycerol, a substance that is normally present in tissues, can serve as a potent inhibitor of cell proliferation. PMID- 1901932 TI - [The use of labelled leukocytes in the diagnosis of traumatic osteomyelitis]. AB - A total of 20 patients with posttraumatic osteomyelitis were investigated with 99mTc- and 111In-labeled leukocytes. Their elevated accumulation in inflammatory zones were detected on scintigrams of 12 patients. Osteomyelitis in 11 of them was confirmed on the basis of routine clinico-laboratory investigations. This method is a highly specific test in the diagnosis of posttraumatic osteomyelitis and in the assessment of the efficacy of its therapy. PMID- 1901933 TI - Effects of 30-h sleep loss on cardiorespiratory functions at rest and in exercise. AB - The effects of 30-h sleep deprivation on cardiorespiratory function either at rest or in exercise were studied in 15 young healthy male volunteers. All subjects performed 1-min incremental exercise tests on a bicycle ergometer until exhaustion and endurance exercise tests at 3/4 of their maximal work rates. Arterialized venous blood samples were withdrawn at rest and during exercise tests to investigate the influence of sleep loss on blood gases. In addition, resting plasma catecholamine levels were also measured in ten subjects. The results showed that 1) resting heart rate, plasma catecholamine levels, and blood pH were decreased while minute ventilation (VI) and CO2 production (VCO2) were increased after 30 h of sleep loss (P less than 0.05), and 2) the maximal exercise performance was reduced by sleeplessness, as indicated by the decreases in the maximal heart rate, peak VI, peak VCO2, peak O2 consumption, and time to exhaustion (P less than 0.05). However, no significant changes in exercise endurance, arterialized venous pH, and PCO2 were found in exercise after sleep deprivation either. We therefore conclude that 30-h sleep loss alters cardiorespiratory function at rest and the ability to perform maximal exercise but not exercise endurance. PMID- 1901935 TI - Withdrawing life-sustaining treatment from severely brain-damaged persons. AB - Ventilator support is commonly withdrawn from unconscious patients who cannot breathe when it is reasonably certain that their condition is permanent and further medical treatment is futile. However, there is no consistent practice with permanently unconscious patients who can breathe but cannot swallow, despite the fact that ongoing treatment of these patients is similarly futile. In both groups of patients, the withdrawal of treatment is not euthanasia, and the cause of death is properly considered to be the underlying illness. A review of the medical, legal and ethical literature shows that there is much disagreement about when and how to withdraw tube feeding from patients with severe brain damage. Criteria for withdrawal of treatment should include the permanent unconsciousness of the patient, the permanent absence of a life-sustaining function, the elapse of sufficient time to be certain about the prognosis, the concurrence of at least one independent and qualified medical specialist, and the informed consent of the patient's family or other legally qualified agents. PMID- 1901934 TI - Results of radiotherapy for localised prostatic carcinoma treated at the Prince of Wales Hospital, Sydney. AB - Between 1980 and 1986 a total of 218 patients with localised prostatic carcinoma received radical pelvic radiotherapy at The Prince of Wales Hospital, Sydney. The mean follow-up time was 4.6 years. The five-year actuarial overall survival rate was 63% (death from all causes) and the five-year cancer-specific survival rate was 73% (death from or with prostate cancer). The overall survival was significantly worse with more advanced clinical stage of the disease (P = 0.003) and with poor histological differentiation of the tumour (P = 0.001). The five year actuarial rate for local control of tumour in the pelvis was 84%. Late treatment-related complications (occurring or persisting beyond six months) were mild or moderate and the majority settled with conservative management. Only five patients experienced severe complications (necessitating surgical treatment). Of 42 patients with normal potency documented before radiotherapy who were not subsequently hormonally manipulated 23 (55%) retained potency at two years. These results for definitive radiotherapy for localised prostatic carcinoma indicate good local control with minimal morbidity and compare favourably with other published results. PMID- 1901936 TI - [Primary amyloidosis and thrombophlebitis as complications of Bence-Jones plasmacytoma (lambda type)]. PMID- 1901937 TI - Courage, creativity, and cost-effectiveness: the challenge for a psychiatric program administration. PMID- 1901938 TI - Ascorbic acid deficiency decreases specific forms of cytochrome P-450 in liver microsomes of guinea pigs. AB - Ascorbic acid (VC) deficiency resulted in a decrease in the activities of aminopyrine N-demethylase, aniline hydroxylase, and p-nitroanisole O-demethylase and in the content of cytochrome P-450, as spectrally determined, whereas it caused an increase in the activities of 6 beta-hydroxylases for testosterone and progesterone in liver microsomes of guinea pigs. Western blot analysis of liver microsomes with antibodies to rat P-448-H (P-4501A2), P-450j (P-450IIE), P-450 PB 1 (P-450IIIA), and P-450b (P-450IIB1) showed that VC deficiency decreased the amount of cytochrome P-450 immunochemically related to P-450IA2 and P-450IIE but did not change the amount of the form that was cross-reactive with antibodies to P-450IIB1 and tended to slightly increase (not statistically significantly) the amount of the form of the cytochrome immunochemically related to P-450IIIA. The larger decrease by VC deficiency in the amount of cytochrome P-450 that was cross reactive to the rat P-450IA2 resulted in a lower capacity of liver microsomes to activate promutagens, such as 2-amino-3-methyl-imidazo(4,5-f)quinoline and aflatoxin B1. These results indicate that VC deficiency in guinea pigs differentially affects the content of individual forms of cytochrome P-450. PMID- 1901939 TI - Directed shift of fatty acids from phospholipids to triacylglycerols in HL-60 cells induced by nanomolar concentrations of triethyl lead chloride: involvement of a pertussis toxin-sensitive pathway. AB - Triethyl lead chloride (Et3PbCl) was found to induce a shift of fatty acids from membrane phospholipids to triacylglycerols in the human promyelocytic leukemia cell line HL-60. High concentrations of Et3PbCl (greater than 10 microM) caused a substantial liberation of [14C]arachidonic acid within 10 to 20 min in dimethyl sulfoxide-differentiated cells, comparable to the effect of the calcium ionophore A23187 (10 microM). Following liberation of arachidonic acid, its metabolites could be detected. Prolongation of the incubation time and reduction of Et3PbCl concentration resulted in a shift of fatty acids from phospholipids to triacylglycerols. Deacylation of phospholipids and reacylation into phospholipids and triacylglycerols were in equilibrium when the cells were treated with Et3PbCl at concentrations of less than or equal to 10 microM for 5 hr or less than or equal to 1 microM for 24 hr; no increase of free fatty acids could be observed, and the loss of fatty acids within the phospholipids was equivalent to the increase of fatty acid content within the triacylglycerols. Moreover, under these conditions, no loss of viability was seen after 24 hr, as compared with untreated differentiated cells. This concentration- and time-dependent effect of Et3PbCl might be due to a stimulated liberation of fatty acids via phospholipase A2, because this stimulation could be totally prevented by the phospholipase inhibitors quinacrine and p-bromophenacylbromide. Additionally, pretreatment of differentiated HL-60 cells with pertussis toxin resulted in a drastic reduction of [14C]arachidonic acid liberation when cells were stimulated with Et3PbCl. These results suggest the involvement of a pertussis toxin-sensitive GTP-binding protein and of a signal transduction mechanism during stimulated fatty acid release; release does not seem to be via a direct stimulation of phospholipase activity by the lead compound. PMID- 1901940 TI - Interleukin-6- and leukemia inhibitory factor-induced terminal differentiation of myeloid leukemia cells is blocked at an intermediate stage by constitutive c-myc. AB - Interleukin-6 (IL-6) and leukemia inhibitory factor (LIF), two multifunctional cytokines, recently have been identified as physiological inducers of hematopoietic cell differentiation which also induce terminal differentiation and growth arrest of the myeloblastic leukemic M1 cell line. In this work, it is shown that c-myc exhibited a unique pattern of expression upon induction of M1 terminal differentiation by LIF or IL-6, with an early transient increase followed by a decrease to control levels by 12 h and no detectable c-myc mRNA by 1 day; in contrast, c-myb expression was rapidly suppressed, with no detectable c myb mRNA by 12 h. Vectors containing the c-myc gene under control of the beta actin gene promoter were transfected into M1 cells to obtain M1myc cell lines which constitutively synthesized c-myc. Deregulated and continued expression of c myc blocked terminal differentiation induced by IL-6 or LIF at an intermediate stage in the progression from immature blasts to mature macrophages, precisely at the point in time when c-myc is normally suppressed, leading to intermediate stage myeloid cells which continued to proliferate in the absence of c-myb expression. PMID- 1901941 TI - Stereospecific alignment of the X and Y elements is required for major histocompatibility complex class II DRA promoter function. AB - The regulatory mechanisms controlling expression of the major histocompatibility complex (MHC) class II genes involve several cis-acting DNA elements, including the X and Y boxes. These two elements are conserved within all murine and human class II genes and are required for accurate and efficient transcription from MHC class II promoters. Interestingly, the distance between the X and Y elements is also evolutionarily conserved at 18 to 20 bp. To investigate the function of the invariant spacing in the human MHC class II gene, HLA-DRA, we constructed a series of spacing mutants which alters the distance between the X and Y elements by integral and half-integral turns of the DNA helix. Transient transfection of the spacing constructs into Raji cells revealed that inserting integral turns of the DNA helix (+20 and +10 bp) did not reduce promoter activity, while inserting or deleting half-integral turns of the DNA helix (+15, +5, and -5 bp) drastically reduced promoter activity. The loss of promoter function in these half-integral turn constructs was due neither to the inability of the X and Y elements to bind proteins nor to improper binding of the X- and Y-box-binding proteins. These data indicate that the X and Y elements must be aligned on the same side of the DNA helix to ensure normal function. This requirement for stereospecific alignment strongly suggests that the X- and Y-box-binding proteins either interact directly or are components of a larger transcription complex which assembles on one face of the DNA double helix. PMID- 1901942 TI - Expression of different Jun and Fos proteins during the G0-to-G1 transition in mouse fibroblasts: in vitro and in vivo associations. AB - We have characterized the expression of c-Jun, JunB, JunD, c-Fos, and FosB proteins following serum stimulation of quiescent Swiss 3T3 cells by immunoprecipitation analyses. The synthesis of the three Jun proteins rapidly increases following stimulation, remaining at a significant level for at least 8 h. JunB protein presents the highest expression of all. FosB, like c-Fos, is transiently induced. Pulse-chase experiments show that all of the proteins except JunD are short-lived. We have shown that c-Fos and FosB form complexes in vivo with the different Jun proteins and that JunB complexes are predominant. In vitro association and competition experiments show that the affinities between the different Fos and Jun proteins are similar. This finding, together with the in vivo observations described above, suggests that the proportion of the different Jun/Fos heterodimers is governed by the concentration of the different components. The Fos and Jun proteins are phosphoproteins, and some remain relatively highly phosphorylated in their heterodimeric form. PMID- 1901943 TI - An A + U-rich element RNA-binding factor regulates c-myc mRNA stability in vitro. AB - Transient expression of some proto-oncogenes, cytokines, and transcription factors occurs as a cellular response to growth factors, 12-O tetradecanoylphorbol-13-acetate, antigen stimulation, or inflammation. Expression of these genes is mediated in part by the rapid turnover of their mRNAs. A + U rich elements in the 3' untranslated regions of these mRNAs serve as one recognition signal targeting the mRNAs for rapid degradation. I report the identification of a cytosolic factor that both binds to the proto-oncogene c-myc A + U-rich element and specifically destabilizes c-myc mRNA in a cell-free mRNA decay system which reconstitutes mRNA decay processes found in cells. Proteinase K treatment of the factor abolishes its c-myc mRNA degradation activity without affecting its RNA-binding capacity. Thus, RNA substrate binding and degradation appear to be separable functions. These findings should aid in understanding how the cell selectively targets mRNAs for rapid turnover. PMID- 1901944 TI - The yeast homolog to mouse Tcp-1 affects microtubule-mediated processes. AB - A Saccharomyces cerevisiae homolog to Drosophila melanogaster and mouse Tcp-1 encoding tailless complex polypeptide 1 (TCP1) has been identified, sequenced, and mapped. The mouse t complex has been under scrutiny for six decades because of its effects on embryogenesis and sperm differentiation and function. TCP1 is an essential gene in yeast cells and is located on chromosome 4R, linked to pet14. The TCP1-encoded proteins in yeast, Drosophila, and mouse cells share between 61 and 72% amino acid sequence identities, suggesting a primordial function for the TCP1 gene product. To assess function, we constructed a cold impaired recessive mutation (tcp1-1) in the yeast gene. Cells carrying the tcp1-1 mutation grew linearly rather than exponentially at the restrictive temperature of 15 degrees C with a generation time of approximately 32 h in minimal medium. Both multinucleate and anucleate cells accumulated with time, suggesting that the linear growth kinetics may be explained by the generation of anucleate buds incapable of further cell division. In addition, the multinucleate and anucleate cells contained morphologically abnormal structures detected by anti-alpha tubulin antibodies. The kinetics of appearance of these abnormalities suggest that they are a direct consequence of loss of function of the TCP1 protein and not a delayed, indirect consequence of cell death. We also observed that strains carrying tcp1-1 were hypersensitive to antimitotic compounds. Taken together, these observations imply that the TCP1 protein affects microtubule-mediated processes. PMID- 1901945 TI - c-fos mRNA expression in macrophages is downregulated by interferon-gamma at the posttranscriptional level. AB - Treatment of macrophages with interferon-gamma (IFN gamma) strongly decreased the induction of c-fos mRNA by 12-O-tetradecanoylphorbol-13-acetate (TPA), lipopolysaccharide, or calcium ionophore A23187 in macrophages. Under the same experimental conditions, IFN gamma induced oligo(A) synthetase mRNA and did not affect the constitutive expression of transforming growth factor beta mRNA, indicating that IFN gamma did not induce general degradation of mRNAs. Run-on experiments indicated that c-fos was constitutively transcribed at low levels and that TPA augmented c-fos transcription. IFN gamma did not inhibit constitutive or TPA-induced c-fos transcription. However, IFN gamma decreased c-fos mRNA stability, as assessed by measuring the half-life of c-fos mRNA in actinomycin D treated cells. These results indicated that IFN gamma inhibited c-fos mRNA induction by TPA at the posttranscriptional level. PMID- 1901946 TI - Identification of a multiprotein complex interacting with the c-fos serum response element. AB - The serum response element (SRE) is essential for serum and growth factor stimulation of the c-fos gene. We have examined the nuclear proteins, obtained from tissues with elevated expression of the c-fos gene (proliferating rat liver and hepatocarcinoma), that bind to the SRE sequence. A synthetic oligonucleotide containing the SRE sequence from the mouse c-fos gene promoter (-299 to -322) was radioactively labeled, used as a probe for the mobility shift assay and Southwestern (DNA-protein) blotting, and also used for sequence-specific affinity chromatography. We have identified a group of nuclear proteins of molecular sizes 36, 45, 62, 67, 72, and 112 kDa capable of interacting with the SRE sequence. The 36-, 67-, and 112-kDa proteins have DNA-binding properties, but the presence of the others in the SRE-protein complex could be the result of protein-protein interaction. All of these protein factors were present in nuclei obtained from intact and proliferating rat liver as well as from 5123tc Morris hepatoma. The DNA-binding activity (on Southwestern blots) of the 67- and 112-kDa proteins was not affected by alkaline phosphatase treatment, but the ability of the dephosphorylated nuclear proteins to form the complex with the SRE sequence under gel shift assay conditions was severely impaired. The same alkaline phosphatase treatment completely abolished the DNA-binding properties of the c-fos cyclic AMP responsive element-specific proteins. Therefore, transcriptional activation of the c-fos gene at the SRE must require the presence of a multiprotein complex the formation of which is governed by phosphorylation. The binding of the 67- and 62 kDa proteins to the c-fos SRE has been previously reported; however, the 36-. 45 , 72-, and 112-kDa proteins are novel factors involved in the multifaceted regulation of c-fos gene expression in vivo. PMID- 1901947 TI - Ras GTPase-activating protein physically associates with mitogenically active phospholipids. AB - The physical interaction between GTPase-activating protein (GAP) and lipids has been characterized by two separate analyses. First, bacterially synthesized GAP molecules were found to associate with detergent-mixed micelles containing arachidonic but not with those containing arachidic acid. This association was detected by a faster elution time during molecular exclusion chromatography. Second, GAP molecules within a crude cellular lysate were specifically retained by a column on which certain lipids had been immobilized. The lipids able to retain GAP on such columns were identical to those which were shown previously to be most active in blocking GAP activity. The association between lipids and GAP was dependent upon magnesium ions. Lipids unable to inhibit GAP activity were also unable to physically associate with GAP. The tight association of GAP with these lipids was predicted by and helps to rationalize their ability to inhibit GAP activity. PMID- 1901948 TI - Rapid and preferential activation of the c-jun gene during the mammalian UV response. AB - Exposure of mammalian cells to DNA-damaging agents leads to activation of a genetic response known as the UV response. Because several previously identified UV-inducible genes contain AP-1 binding sites within their promoters, we investigated the induction of AP-1 activity by DNA-damaging agents. We found that expression of both c-jun and c-fos, which encode proteins that participate in formation of the AP-1 complex, is rapidly induced by two different DNA-damaging agents: UV and H2O2. Interestingly, the c-jun gene is far more responsive to UV than any other immediate-early gene that was examined, including c-fos. Other jun and fos genes were only marginally affected by UV or H2O2. Furthermore, UV is a much more efficient inducer of c-jun than phorbol esters, the standard inducers of c-jun expression. This preferential response of the c-jun gene is mediated by its 5' control region and requires the TPA response element, suggesting that this element also serves as an early target for the signal transduction pathway elicited by DNA damage. Both UV and H2O2 lead to a long-lasting increase in AP-1 binding activity, suggesting that AP-1 may mediate the induction of other damage inducible genes such as human collagenase. PMID- 1901949 TI - c-fos gene transcription in murine macrophages is modulated by a calcium dependent block to elongation in intron 1. AB - Cultured mouse thioglycolate-elicited peritoneal macrophages exhibit a strong block to transcriptional elongation beyond the end of the c-fos gene first exon. This block is absent in freshly isolated peritoneal cells, appears slowly during culture, and does not require adherence of the cells. The extent of this block is largely responsible for the levels of c-fos mRNA in cultured macrophages, even after modulation by agents such as the tumor promoter phorbol myristate acetate and increased intracellular cyclic AMP, which also increase the activity of the c fos promoter. When macrophages are cultured in the absence of mobilizable calcium, the block can no longer be relieved by any inducing agent. Conversely, upon calcium influxes, there is little alteration in the level of transcriptional initiation, but transcription proceeds efficiently through the entire c-fos locus. These results suggest the presence of an intragenic calcium-responsive element in the c-fos gene and illustrate its key role in the control of c-fos gene transcription. PMID- 1901950 TI - Sequence requirements for premature transcription arrest within the first intron of the mouse c-fos gene. AB - A strong block to the elongation of nascent RNA transcripts by RNA polymerase II occurs in the 5' part of the mammalian c-fos proto-oncogene. In addition to the control of initiation, this mechanism contributes to transcriptional regulation of the gene. In vitro transcription experiments using nuclear extracts and purified transcription templates allowed us to map a unique arrest site within the mouse first intron 385 nucleotides downstream from the promoter. This position is in keeping with that estimated from nuclear run-on assays performed with short DNA probes and thus suggests that it corresponds to the actual block in vivo. Moreover, we have shown that neither the c-fos promoter nor upstream sequences are absolute requirements for an efficient transcription arrest both in vivo and in vitro. Finally, we have characterized a 103-nucleotide-long intron 1 motif comprising the arrest site and sufficient for obtaining the block in a cell free transcription assay. PMID- 1901952 TI - A mammalian inhibitory GDP/GTP exchange protein (GDP dissociation inhibitor) for smg p25A is active on the yeast SEC4 protein. AB - Evidence is accumulating that smg p25A, a small GTP-binding protein, may be involved in the regulated secretory processes of mammalian cells. The SEC4 protein is known to be required for constitutive secretion in yeast cells. We show here that the mammalian GDP dissociation inhibitor (GDI), which was identified by its action on smg p25A, is active on the yeast SEC4 protein in inhibiting the GDP/GTP exchange reaction and is capable of forming a complex with the GDP-bound form of the SEC4 protein but not with the GTP-bound form. These results together with our previous findings that smg p25A GDI is found in mammalian cells with both regulated and constitutive secretion types suggest that smg p25A GDI plays a role in both regulated and constitutive secretory processes, although smg p25A itself may be involved only in regulated secretory processes. These results also suggest that a GDI for the SEC4 protein is present in yeast cells. PMID- 1901951 TI - Molecular cloning of the cDNA for stimulatory GDP/GTP exchange protein for smg p21s (ras p21-like small GTP-binding proteins) and characterization of stimulatory GDP/GTP exchange protein. AB - We have recently purified to near homogeneity the stimulatory GDP/GTP exchange protein for smg p21s (ras p21-like GTP-binding proteins) from bovine brain cytosol. This regulatory protein, named GDP dissociation stimulator (GDS), stimulates the GDP/GTP exchange reaction of smg p21s by stimulating the dissociation of GDP from and the subsequent binding of GTP to them. In this study, we have isolated and sequenced the cDNA of smg p21 GDS from a bovine brain cDNA library by using an oligonucleotide probe designed from the partial amino acid sequence of the purified smg p21 GDS. The cDNA has an open reading frame encoding a protein of 558 amino acids with a calculated Mr value of 61,066, similar to the Mr of 53,000 estimated for the purified smg p21 GDS by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and sucrose density gradient ultracentrifugation. The isolated cDNA is expressed in Escherichia coli, and the encoded protein exhibits smg p21 GDS activity. smg p21 GDS is overall hydrophilic, but there are several short hydrophobic regions. The smg p21 GDS mRNA is present in bovine brain and various rat tissues. smg p21 GDS has low amino acid sequence homology with the yeast CDC25 and SCD25 proteins, which may regulate the GDP/GTP exchange reaction of the yeast RAS2 protein, but not with ras p21 GTPase-activating protein, the inhibitory GDP/GTP exchange proteins (GDP dissociation inhibitor) for smg p25A and rho p21s, and the beta gamma subunits of heterotrimeric GTP-binding proteins such as Gs and Gi. PMID- 1901954 TI - Calcium/calmodulin regulation of the rat prolactin gene is conferred by the proximal enhancer region. AB - The effects of the calcium/calmodulin signaling system on expression of the rat PRL gene were studied in rat pituitary GH3 cells using two specific naphthalene sulfonamide calmodulin (CaM) antagonist drugs, W7 and a more potent and more highly specific iodo-derivative, 5-iodo-1-C8. PRL (but not GH) mRNA accumulation was markedly inhibited by W7, which in coincubations abolished the stimulation normally seen with TRH. Transient transfection assays showed that expression of the reporter gene chloramphenicol acetyl transferase (CAT) linked to 5'-flanking sequences from the PRL gene was inhibited by the calcium-channel blocker verapamil and by the two CaM antagonists. The calcium effects showed partial promoter specificity, in that transcription of PRL-CAT constructs was markedly inhibited by verapamil, but the Rous sarcoma virus-CAT construct also showed significant inhibition, whereas the pBL-CAT2 construct was unaffected. Three hundred ninety five base pairs were sufficient to confer the full inhibitory effect of calcium channel blockade or CaM antagonist seen with longer constructs. The data indicate that CaM is important for PRL gene transcription, and that the effects of CaM are exerted on DNA sequences within the proximal 395bp of prolactin 5'-flanking DNA. PMID- 1901955 TI - Development of a species-specific DNA probe for Moraxella (Branhamella) catarrhalis. AB - Moraxella (Branhamella) catarrhalis is an aerobic Gram-negative diplococcus that is now recognized as a pathogen of the respiratory tract. Rapid and direct identification of this bacterium has become important to the clinical microbiology laboratory. Recently, rapid tests for the identification of Neisseria species and M. catarrhalis have been commercialized but they are primarily for Neisseriae; in these kits, M. catarrhalis is always identified presumptively. We have developed a DNA probe of chromosomal origin that is 100% specific for M. catarrhalis. The oligonucleotide probe was derived from a cloned Ase I chromosomal DNA fragment of M. catarrhalis that did not react with Haemophilus influenzae DNA in hybridization experiments. Three of the first 17 Ase I clones were selected randomly to be tested by colony hybridization against several different species that colonize the human respiratory tract. One of these three, pLQ121, has a 550 bp fragment inserted into pBR322 and was determined to be 100% specific to M. catarrhalis. This fragment was partially sequenced and a 30-mer oligonucleotide was synthesized from the sequence data. This probe was also shown to be 100% specific to the species. PMID- 1901953 TI - Measurement of peptide secretion and gene expression in the same cell. AB - A combined reverse hemolytic plaque-in situ hybridization assay was developed to allow analysis of the relationship between peptide secretion and gene expression within individual cells. We used the pituitary lactotroph as a model system, but this strategy should be widely applicable. It can be used to test hypotheses regarding if and when peptide secretion and gene expression are coupled in any system in which antibodies to the secreted peptide and probes complementary to the mRNA are available. Using the mRNA hybridization signal to identify certain cell types, this method may also be useful in further studies on the biochemical mechanism of peptide secretion. In addition, questions regarding whether a cell known to secrete a given peptide contains other specific mRNAs and the relationship between these mRNAs and the secretion of the peptide can be studied using this strategy. We found striking heterogeneity among lactotrophs in both gene expression and PRL secretion and a lack of correlation of these parameters within individual lactotrophs under every treatment examined. We also present the first direct visualization and quantitation of the percentage of nonsecreting PRL mRNA-containing cells after estradiol treatment and in the presence or absence of the PRL secretagogue, TRH. Finally, we found that in ovariectomized rats, nonsecreting lactotrophs exhibited significantly higher levels of PRL mRNA than lactotrophs that were actively secreting PRL during the assay. PMID- 1901956 TI - Evaluation of a DNA probe of plasmid origin for the detection of Neisseria gonorrhoeae in cultures and clinical specimens. AB - This study evaluates a cryptic plasmid-derived DNA probe in a dot-blot hybridization assay of 4-h duration, using both known bacterial isolates and clinical specimens. The probe, consisting of a 237 bp segment of the plasmid encoded gene cppB, sequences of which are also found in the chromosome, was labelled with digoxigenin-11-dUTP. The sensitivity of the probe was approximately 25 pg of DNA or 500 cfu of Neisseria gonorrhoeae. A total of 170 reference strains of Neisseria gonorrhoeae and other related bacteria were tested for reactivity with the probe. All N. gonorrhoeae strains, including three plasmid free strains, hybridized with the probe. Among the heterologous bacterial cultures, only one strain of N. cinerea reacted with the probe when the cell concentration was 5 x 10(6) cfu. The probe was also evaluated in a clinical study. A total of 201 patients visiting the STD clinic at the University Hospital, University of Seville, participated in the study. The sensitivity of the assay was 95% while the specificity was 98%. Positive and negative predictive values were 97% and 98%, respectively. It appears that the plasmid-derived probe used in this study could serve as a useful tool in the rapid and specific detection of Neisseria gonorrhoeae in clinical specimens. PMID- 1901957 TI - The genotoxicities of N-nitrosamines in Drosophila melanogaster in vivo: the correlation of mutagenicity in the wing spot test with the DNA damages detected by the DNA-repair test. AB - The genotoxicities of a series of N-nitrosamines were assayed in the wing spot test and a new short-term test of Drosophila melanogaster. In the spot test, larval flies trans-heterozygous for the somatic cell markers mwh and flr3 were fed the test reagents and the wing hairs in adults were inspected for clones expressing the phenotypes of the markers. In the other test, larval stock consisting of meiotic recombination-deficient (Rec-) double mutant mei-9a and mei 41D5 males and repair-proficient Rec+ females were grown on feed containing the reagents and the DNA damages were detected with the preferential killing of the Rec- larvae as an endpoint. The carcinogenic nitrosamines tested, N nitrosodimethylamine (NDMA), N-nitrosodiethylamine (NDEA), N-nitrosodi-n butylamine (NDBA), N-nitrosomorpholine (NMOR), N-nitro-sopiperidine (NPIP) and N nitrosopyrrolidine (NPYR), all showed clearly positive activities in both tests. The activities in the wing spot test were ranked in a sequence of NDMA much greater than NMOR greater than NPIP greater than NDEA greater than NPYR greater than NDBA. A similar ranking was obtained in the repair assay. The genotoxicity of N-nitrosodiphenylamine (NDPhA), carcinogenicity studies of which are inconclusive, was marginal in the spot test. The non-carcinogenic N nitrosoproline (NPRO) and the non-mutagenic N-nitrosothioproline (NTPRO) were negative in the spot test. NDPhA and NPRO were negative in the repair test as well. The DNA-repair test is thus a convenient technique for estimating the mutagenicity of compounds because of its simplicity compared with the wing spot test. These Drosophila tests may be useful in predicting carcinogenic potentials of compounds. PMID- 1901958 TI - The genotoxicity of nitrilotriacetic acid (NTA) in a somatic mutation and recombination test in Drosophila melanogaster. AB - The genotoxicity of a chelating agent, the trisodium salt of nitrilotriacetic acid (NTA), was assessed in a somatic mutation and recombination test (SMART) in Drosophila melanogaster employing the wing hair markers mwh and flr3. The experiments were performed in parallel in two different laboratories (Padua, Italy and Schwerzenbach, Switzerland). The effectively absorbed doses of NTA, which was administered by feeding to larvae, were determined by a sensitive method employing [3H]leucine which allowed individual consumption levels to be measured. The particular pattern of clone induction produced by this compound suggests that NTA is active in inducing mitotic recombination and possibly aneuploidy in somatic cells of Drosophila. This is discussed in relation to the data present in the literature regarding the genotoxicity of NTA in a variety of experimental systems. PMID- 1901959 TI - Avoiding bias in the conduct and reporting of cost-effectiveness research sponsored by pharmaceutical companies. PMID- 1901960 TI - The end for monkeys. PMID- 1901962 TI - Indirect evidence for transfusion role in conditioning hepatitis C virus prevalence among dialysis patients. PMID- 1901963 TI - Anatomical interactions of proopiomelanocortin (POMC)-related peptides, neuropeptide Y (NPY) and dopamine beta-hydroxylase (D beta H) fibers and thyrotropin-releasing hormone (TRH) neurons in the paraventricular nucleus of rat hypothalamus. AB - In order to determine the nature of afferent fibres contacting thyrotropin releasing hormone (TRH)-synthesizing neuronal cell bodies in the rat hypothalamic paraventricular nucleus, we used dual immunostaining procedures which employed antibodies to ACTH (to label proopiomelanocortin (POMC) neurons), neuropeptide Y (NPY) and dopamine-beta-hydroxylase (D beta H) and peroxidase-labeled goat anti rabbit IgG as a first sequence and antibodies to a cryptic fragment (Phe178 Glu199) of pro-TRH (to label TRH neurons) and alkaline phosphatase-labeled goat anti-rabbit IgG as the second sequence. A rich innervation of the paraventricular nucleus by immunoreactive POMC, NPY and D beta H fibres was observed. Numerous NPY and POMC fibres were in intimate anatomic proximity and often appeared to surround in remarkable density TRH-containing cell bodies. Less frequent appositions between D beta H fibres and TRH cell bodies were detected. These results strongly suggest that TRH neurons might be regulated by POMC, NPY as well as adrenergic and/or noradrenergic systems. These interactions might be the neuroanatomical basis for the already observed effects of opiate peptides, NPY and catecholamines on TSH secretion. PMID- 1901961 TI - Alzheimer's mutation. PMID- 1901964 TI - Central ventilatory effects of thyrotropin-releasing hormone in the conscious rat. AB - Thyrotropin-releasing hormone was shown to exert potent ventilatory effects after central administration. These data, however, were derived from studies using anesthetized animal preparations. Since TRH elicits strong arousal reactions, the observed ventilatory effects of TRH under anesthesia may have been due to nonspecific reduction in the anesthetic state of the animals. In order to clarify the extent to which the reversal of anesthesia may change ventilatory parameters after TRH application, we investigated the effect of TRH on ventilation rate, relative tidal volume, relative respiratory minute volume, CO2 production CO2 consumption, and locomotor activity in the conscious, unrestrained rat. Intracerebroventricular application of TRH induced a dose-dependent, sustained increase in ventilation rate, relative tidal volume, and relative respiratory minute volume of maximally 128%, 890%, and 235%, respectively. In addition, CO2 production and O2 consumption were elevated by 4.6 and 11.7 fold, while no significant changes in locomotor activity were observed. The results suggest that TRH stimulates ventilation by a mechanism independent of its analeptic properties. PMID- 1901965 TI - Contribution of the right frontal lobe to the encoding and recall of kinesthetic distance information. AB - Sixty-two patients with unilateral temporal- or frontal-lobe excisions and 16 normal control subjects were tested on a kinesthetic task, which required the monitoring of peripheral feedback in order to duplicate the distance of examiner defined arm movements. Temporal lobectomy did not interfere with performance. Patients with left frontal-lobe or small right frontal-lobe excisions also performed normally, whereas those with large right frontal-lobe removals were impaired, the deficit being equal for the two arms. The results point to an important role played by the right frontal lobe in the monitoring of kinesthetic feedback both during the presentation of the movements and during the recall attempt. PMID- 1901966 TI - Mandatory HIV testing and the duty to screen. PMID- 1901967 TI - Surgical endoscopy training: benefit to army-wide medicine. AB - To assess the benefit of surgeons being trained in endoscopic procedures, the gastrointestinal endoscopic experience of all surgical residents graduating from a single medical center in the 1984-87 period was evaluated. For the 1989 1-year period, the surgeons' aggregate total of gastrointestinal endoscopic procedures was 1,040: 470 EGDs and 570 colonoscopies. During a 3-year (1987-89) period, the total was 2,290 procedures: 1,080 EGDs and 1,210 colonoscopies. While the cost savings for over 1,000 endoscopic procedures a year is obvious, it is the impact of the accessibility of these procedures on quality patient care that is of the greatest benefit. In this era of financial constraints and personnel cutbacks, the incorporation of gastrointestinal endoscopy into surgical training must be insured and surgeons must be encouraged to pursue their endoscopic skills throughout their surgical careers. PMID- 1901968 TI - Management of uncomplicated acute myocardial infarction: are there differences in patterns of care between VAMC physicians and private practice physicians? AB - Uncomplicated acute myocardial infarction is a diagnostic category in which significant changes in patterns of care have occurred in the past 17 years. In this retrospective study, a comparison has been made between actual practice patterns of VA physicians and those reported in literature. Findings demonstrated differences in: length of stay in a monitored bed-5 days vs. 2.8 days; drug preferences--calcium antagonists and nitrates vs. nitrates and plasminogen activators; pre-discharge diagnostic studies--cholesterol/triglyceride levels and coronary angiography vs. lipid levels and exercise electrocardiograms; and patient education--follow-up appointments and diet vs. smoking cessation, diet, and exercise programs. PMID- 1901969 TI - HIV infection: military occupational sequelae. AB - The military experience of 573 soldiers found to be HIV seropositive and their 2,262 matched seronegative controls were compared to determine if differences exist. Examination of personnel records for study members showed an expected difference in assignment changes, with seropositives being moved significantly more often to other units in compliance with a regulation prohibiting their presence in special operations units and units located overseas. Otherwise, there was no statistically significant difference at the 0.05 level when comparing changes in education, military occupational specialty code, promotion, or demotion. Seropositive individuals were less likely to marry, but no more likely to divorce. Seropositives were more likely to be separated from active service and barred from reenlistment for medical reasons. PMID- 1901970 TI - Prevalence of burnout among military dentists. AB - Burnout is a syndrome of emotional exhaustion, depersonalization, and reduced personal accomplishment that can occur among individuals who do "people work" of some kind. Health care providers, including dentists, are at high risk for burnout because their occupations often require intense interactions between themselves and fearful, demanding patients on a daily basis. The purpose of this study was to assess the prevalence of burnout among military dentists practicing at a large installation using a standardized measurement device, the Maslach Burnout Inventory. Results indicate that the military dentists surveyed experience low to moderate levels of burnout. The military dentists sampled, in general, scored lower for burnout when compared to the norms of society and medicine. PMID- 1901971 TI - Functional restoration following anterior cruciate ligament reconstruction in active-duty military personnel. AB - A retrospective review was conducted of 112 active-duty military patients receiving anterior cruciate ligament reconstruction between 1985 and 1987. Mean age of these patients was 26.4 years, average follow-up was 2.35 years, and the average interval from time of injury to reconstruction was 13.6 months. The three most commonly employed surgical techniques were the Andrews' iliotibial band tenodesis, mid-third patellar tendon autograft, and a combined Andrews' and mid third patellar tendon reconstruction. Seventy-eight patients (69.6%) returned to full duty and the ultimate disposition was not affected by the reconstructive procedure performed, chronicity of injury, or sex. A statistically higher percentage of patients over 30 years old returned to full unrestricted military service than did patients under 30. Associated posterior cruciate injury and degenerative joint disease resulted in poorer results. Our results demonstrate that functional restoration, based on the occupational criteria of return to full unrestricted duty, is likely following anterior cruciate ligament reconstruction. PMID- 1901972 TI - Psychiatric care of the homeless mentally ill: an opportunity for military psychiatry training. AB - This paper reviews the phenomenon of homelessness in the United States and locally in Washington, D.C. Prevalence data of psychiatric illness in the homeless is presented, as is the formation of a psychiatric service network to treat the homeless mentally ill. Additionally, the author describes the development of an innovative training program in community psychiatry, focusing specifically on issues inherent in understanding the work of the psychiatric resident in community-based training and service delivery. The relevance of this experience to military medicine involves training psychiatric residents to develop service-delivery schemes in times of rapidly expanding mental health needs, such as combat. PMID- 1901973 TI - Eye casualty reduction by eye armor. PMID- 1901974 TI - Considerations on propofol administration in the field anesthesia setting (Echelons II and III). PMID- 1901975 TI - Formula for success: the role of the MSC officer and the U.S. Army dental care system. AB - The Army dental care system has seen significant improvements since the Dental Reform Bill of 1977-1978. This bill initiated changes that improved the management and the productivity of the dental care system. Among the many improvements initiated by these reforms was the addition of a Medical Service Corps (MSC) officer as the executive officer. This has been most noteworthy in the successful management of Dental Activities (DENTAC) and Area Dental Labs on Army installations. The job of DENTAC executive officer has become very prestigious and one of the best assignments an MSC officer can receive during his military career. The alliance between the Dental Corps and the MSC officer has been highly successful and rewarding to both parties. The object of this paper is threefold: (a) to review how the dental organization operated before the Reform Bill; (b) to discuss the present role of the dental Executive Officer; and (c) to provide recommendations for the future role of the MSC officer within the Dental Corps. PMID- 1901976 TI - Computed tomography of the brain in the evaluation of the headache patient. AB - A retrospective analysis was conducted of 100 consecutive patients evaluated with computerized tomography of the head who had the chief complaint of headache. Three percent of these patients had abnormal findings, which were clinically significant in terms of patient treatment and follow-up. An additional 10% had computed tomography findings, which were clinically insignificant in that they did not alter the patient's treatment or clinical course. All of the significant findings occurred in patients who were age 45 years or older. In the 85 patients who were less than age 45, no significant abnormalities were found. PMID- 1901977 TI - Hypothermia: threat to military operations. AB - Hypothermia has altered the course of military history. Military casualties tend to occur in epidemics, associated with cold weather combat or maneuvers, trauma, immobilization, improper clothing, exhaustion, and underlying illness. Symptoms of hypothermia begin subtly with fatigue and loss of concentration, but progress to stupor, coma, and resemble rigor mortis. Treatment of mild hypothermia is with body heat and warm clothes and fluids. Moderate and severe cases require gentle evacuation and active core rewarming method(s). Inhalation of warm (40 degrees C, 104 degrees F) humidified oxygen is safe, effective, and can be begun in the field. Recognition of risk factors and active measures can lessen the menance of cold weather for military personnel. PMID- 1901978 TI - Surgical treatment of pilonidal disease: comparison of three different methods in fifty-nine cases. AB - The surgical treatment of pilonidal disease at the Robert Packer Hospital from 1983 to 1989 was reviewed. During that period, 59 patients were operated on for definitive treatment of the disease. The different methods of treatment, namely excision and packing (28 cases), marsupialization (11 cases), and excision and primary closure (20 cases) were compared in terms of age and sex distribution, length of hospital stay, number of post-operative visits, time required for complete healing, complications, and recurrence rate. The operations were performed by surgical residents under the supervision of board-certified surgeons. The average time for complete healing was 21 weeks, 8 weeks, and 3 weeks, respectively, for the different methods. Recurrence rates were essentially nil for all methods. It was concluded that excision and primary closure is the superior method in the treatment of pilonidal disease. The relevant literature was reviewed and the surgical technique discussed. PMID- 1901979 TI - Pulmonary embolization of a vascular ligature clip as a complication of para aortic lymph node sampling. AB - A case is reported of a 57-year-old woman who underwent cytoreductive surgery for stage III, grade 2 endometrioid cystadenocarcinoma of the ovary. During para aortic lymph node sampling, hemostasis was achieved with medium and small metallic ligature clips. The immediate postoperative period was uneventful and the chest radiograph was unchanged from preoperative film. On the sixth postoperative day a chest radiograph showed a radio-opaque object consistent with a metallic ligature clip in the peripheral left middle lung field. The remaining postoperative course was uncomplicated and the patient is well 14 months postoperatively; the ligature clip is unchanged in position. This is an interesting and previously unreported complication of para-aortic lymph node sampling. The means by which the clip entered the vascular system is unknown. Nonsurgical removal of the clip was not feasible due to its peripheral location. No studies exist as to the long-term outcome of foreign bodies embolized to the peripheral lung. PMID- 1901980 TI - Lower extremity lymphocele development after saphenous vein harvesting. AB - Damage to the lymphatic vessels may occur after surgery on the greater saphenous vein. We describe the development of a lymphocele in a patient after saphenous vein harvesting for a coronary artery bypass graft. Treatment of these lymphoceles should initially be conservative, but if this approach fails, surgical excision should be performed and special attention paid to identifying and ligating the feeding lymphatic vessel. PMID- 1901981 TI - Perforation by a foreign body through a pre-existing radial keratotomy wound. AB - A case is presented demonstrating selective perforation of a foreign body through a pre-existing partial thickness radial keratotomy wound. This is the initial documentation of a distinct type of injury to which an eye is susceptible following corneal refractive procedures. Despite the excellent outcome, the occurrence of this injury in a soldier during a field training exercise provides additional justification for current Army policy of barring the induction of enlistees who have undergone corneal surgery to correct refractive errors. PMID- 1901983 TI - [Changes in resistance of Pseudomonas aeruginosa to beta-lactams in a general intensive care unit over a three-year period. Role of piperacillin]. AB - Nosocomial infections by Pseudomonas aeruginosa seen in a general intensive care unit from January 1987 through December 1989 were studied. Use of piperacillin, ticarcillin, cefsulodine, ceftazidime, and imipenem over the same period were recorded. Rate of infection by P. aeruginosa among the 1,844 patients admitted during the study period was 3.2%; 32% of all nosocomial infections during this period were due to P. aeruginosa. The proportion of P. aeruginosa strains exhibiting in vitro susceptibility to ticarcillin rose from 45.5% in 1987 to 59% in 1988 and 86% in 1989. Concomitantly, the proportion of P. aeruginosa strains simultaneously resistant to ticarcillin, piperacillin, cefsulodine and ceftazidime fell from 32% to 18.5% then 0%. A statistically significant correlation was found between the decrease in piperacillin use and the fall in penicillinase-producing ticarcillin-resistant strains of P. aeruginosa. Because piperacillin has undesirable effects on the intestinal flora and promotes the emergence of resistant strains of P. aeruginosa, the authors now use narrow spectrum antimicrobial agents as first line treatment of nocosomial infections. PMID- 1901982 TI - [Partial continuous epilepsy caused by pharmacological treatment with anorectics. A clinical case]. PMID- 1901985 TI - [In vitro activity of an antiseptic, chlorquinaldol, against Neisseria gonorrhoeae and Chlamydia trachomatis]. AB - The activity of chlorquinaldol, a derivative of hydroxy-8-quinolein used for local antisepsy, was studied against Neisseria gonorrhoeae and Chlamydia trachomatis. The weak solubility of the product and the special growth conditions of the organisms made an adaptation of the AFNOR norm necessary. For 0.1 to 0.2% (W/V) chlorquinaldol concentrations, a reduction of about 10(4) organisms was obtained after 60 minutes for N. gonorrhoeae and C. trachomatis. However, for technical problems, the concentrations tested were 10 to 100 times lower than the doses usually recommended for this antiseptic. PMID- 1901984 TI - [Seroprevalence of hepatitis C in human immunodeficiency virus infected patients]. AB - Prevalence of antibodies against hepatitis C virus (HCV) was evaluated using Ortho and Abbott HCV Elisa assays and the Abbott EIA Neutralization assay in 150 human immunodeficiency virus (HIV)-seropositive patients and compared with the prevalence of hepatitis B virus (HBV) and hepatitis D virus (HDV) markers. Overall prevalence of hepatitis C virus antibodies was 29.3%; significant variations were seen across human immunodeficiency virus risk factor subgroups: prevalence was 10.2% in homosexual men, 12.0% in bisexual men, 73.5% in intravenous drug users, 13.3% in blood transfusion recipients, and 16.6% in frequent travellers. Seroprevalence was higher in the 20 to 40 year-old age group and in patients stage II or III according to the Center for Disease Control classification. Prevalence of hepatitis B virus and hepatitis D virus markers (75.7% and 17.5% respectively) was analyzed according to hepatitis C virus marker status; patients with HBcAb were more likely to have antibodies against hepatitis C virus than their HBcAb-negative counterparts. Further studies are needed to investigate the influence of coexposure to human immunodeficiency virus and hepatitis C virus on liver lesions. Data from this study show that coinfection or coexposure is common. PMID- 1901986 TI - [Genetics of cancerogenesis. Experimental model in mice]. PMID- 1901987 TI - Studies of the thymus in Chagas' disease: III. Colonization of the thymus and other lymphoid organs of adult and newborn mice by Trypanosoma cruzi. AB - Among newborn and adult euthymic and athymic mice infected intraperitoneally with 10(2) or 10(4) trypomastigotes, neonates and adult athymic animals exhibited greater susceptibility with heavier colonization of central and peripheral lymphoid organs. Contiguity was also found to be a significant factor in colonization: after similar inocula, the parasitic load in the thymus was comparable in adults and neonates when the former were infected by subcutaneous injection in the anterior neck. In the nude athymic mice, the Y (reticulotropic) strain and the CL (myotropic) strain exhibited similar invasiveness, suggesting that the host immune response modulated the tissular tropism of these strains seen in the heterozygous littermates (Nu/+). The bone marrow was heavily infected; parasites were found in chondrocytes and cells of the mononucleate phagocytic system. Ultrastructural studies of infected thymus specimens showed that the corticomedullary architecture was unaltered and that both macrophages and epithelial cells were infected: both these cell types were infected in vitro. PMID- 1901988 TI - Non-leucine residues in the leucine repeats of Fos and Jun contribute to the stability and determine the specificity of dimerization. AB - Various transcription factors, including C/EBP, GCN4 and members of the Fos, Jun and Myc families have been shown to form highly specific complexes via alpha helical structures referred to as leucine zippers. Experimental evidence has suggested that dimerization involves the formation of hydrophobic bonds between leucine residues in laterally aligned coiled coil structures. However, the specificity of interaction between leucine zipper proteins is not understood. In this study, we show that amino acids, which are located in positions a, e, and g are instrumental in the formation of Fos/Jun heterodimers, presumably by establishing intermolecular electrostatic and hydrophobic interactions. These residues are highly conserved in proteins of the Fos or Jun families but completely different between Fos and Jun, suggesting that these residues determine the specificity of interaction. This conclusion is supported by the observation that the substitution of amino acids in position a or g in Fos with the corresponding Jun amino acids facilitates the association of two Fos leucine repeats. In addition, we show that a conserved histidine residue, located 7 amino acids (i.e., two alpha-helical turns) C-terminally to the 5th leucine in Fos and Jun, is also important for complex formation. PMID- 1901989 TI - Characterization of the cloned BamHI restriction modification system: its nucleotide sequence, properties of the methylase, and expression in heterologous hosts. AB - The BamHI restriction modification system was previously cloned into E. coli and maintained with an extra copy of the methylase gene on a high copy vector (Brooks et al., (1989) Nucl. Acids Res. 17, 979-997). The nucleotide sequence of a 3014 bp region containing the endonuclease (R) and methylase (M) genes has now been determined. The sequence predicts a methylase protein of 423 amino acids, Mr 49,527, and an endonuclease protein of 213 amino acids, Mr 24,570. Between the two genes is a small open reading frame capable of encoding a 102 amino acid protein, Mr 13,351. The M. BamHI enzyme has been purified from a high expression clone, its amino terminal sequence determined, and the nature of its substrate modification studied. The BamHI methylase modifies the internal C within its recognition sequence at the N4 position. Comparisons of the deduced amino acid sequence of M. BamHI have been made with those available for other DNA methylases: among them, several contain five distinct regions, 12 to 22 amino acids in length, of pronounced sequence similarity. Finally, stability and expression of the BamHI system in both E. coli and B. subtilis have been studied. The results suggest R and M expression are carefully regulated in a 'natural' host like B. subtilis. PMID- 1901990 TI - Nucleotides in precursor tRNAs that are required intact for catalysis by RNase P RNAs. AB - Precursor tRNAAsp molecules, containing a 26-base 5' leader, were treated with diethylpyrocarbonate, 50% hydrazine or anhydrous hydrazine/3M NaCl and then subjected to processing by RNase P RNAs from Escherichia coli or Bacillus subtilis. Fully processed tRNAs and material not successfully cleaved by the catalytic RNAs were analyzed for their content of chemically altered nucleotides. Several bases were identified as being required intact for optimal activity as substrate as judged by exclusion of chemically modified residues from processed molecules, and simultaneous enhancement in material that was not recognized as substrate. Such nucleotides cluster near the site of cleavage at the mature 5' end and in the T stem and loop. Purines at residues 1 and 2 adjacent to the site of cleavage, position 57 in the T loop, and site 64 in the T stem exhibited the most pronounced effects. These results suggest a model of recognition of substrate by RNase P RNAs in which the ribozyme interacts with the corner of the precursor tRNA's three dimensional structure, where the T- and D-loops are juxtaposed, and extends along the top of the molecule back towards the site of catalysis. PMID- 1901992 TI - Effects of capsaicin on rat liver S9-mediated metabolism and DNA binding of aflatoxin. AB - At concentrations of 25, 50, and 100 microM, capsaicin, which is the major component in various aspects of Capsicum hot peppers, decreased the binding of aflatoxin (AFB1) to calf thymus DNA by 19%, 44%, and 71%, respectively, in incubations with rat liver S9. At concentrations of 50 and 100 microM, capsaicin decreased the formation of AFB-DNA adducts (AFB1-N7-Gua) by 53% and 75% as determined by high-pressure liquid chromatography (HPLC). HPLC analysis of organo soluble fractions showed that these effects correlated with a concentration dependent decrease in S9-mediated metabolism of AFB1 by capsaicin. Capsaicin also altered the formation of water-soluble conjugates of AFB1. This was indicated by a decrease in radioactivity in water-soluble fractions and in glutathione conjugates of AFB1 analyzed by HPLC. These results suggest that capsaicin inhibited the biotransformation of AFB1 by modifying Phase I hepatic enzyme activity. PMID- 1901991 TI - An enhancer at the 3' end of the mouse immunoglobulin heavy chain locus. AB - A tissue-specific enhancer (E mu) lies between the joining (JH) and mu constant region (C mu) gene segments of the immunoglobulin heavy chain (IgH) locus. Since mouse endogenous IgH genes are efficiently transcribed in its absence, the normal function of this enhancer remains ill-defined. Recently, another lymphoid specific enhancer of equal strength has been identified 3' of the rat IgH locus. We have isolated an analogous sequence from mouse and have mapped it 12.5 kb 3' of the 3'-most constant region gene (C alpha-membrane) of the BALB/c mouse locus. The mouse and rat sequences are 82% homologous and share with other enhancers several DNA sequence motifs capable of binding protein. However, in transient transfection assays, the mouse sequence behaves as a weaker enhancer. The role of this distant element in the expression of endogenous IgH genes, both in E mu deficient, Ig-producing cell lines and during normal B cell development, is discussed. PMID- 1901993 TI - Research note: bioavailability of copper in cupric oxide, cuprous oxide, and in a copper-lysine complex. AB - Young chicks were used in a 2-wk feeding study to evaluate Cu bioavailability (relative to CuSO4.5H2O used as a reference standard) in analytical grade CuO, Cu2O, and in a feed-grade Cu-lysine complex. A basal corn and soybean meal diet was formulated to contain 290 mg Cu/kg, and graded levels (0, 75, and 150 mg/kg) of supplemental Cu were added from each Cu source. Based upon accumulation of Cu in the liver, Cu2O and Cu-lysine furnished Cu as efficiently as CuSO4.5H2O, but CuO provided no bioavailable Cu to the chicks. PMID- 1901996 TI - Determination of carbon dioxide detection thresholds in trained rats. AB - Concentration-response functions for the detection of CO2 were established for six rats. The animals were tested in a wind tunnel apparatus and trained using standard operant techniques and a discrete trials, go, no-go successive discrimination paradigm. The primary conclusion to be drawn from the performance measurements is that, at least under carefully controlled conditions, rats can detect physiologic concentrations of CO2 (0-4%). Minimum detectable concentrations fell within the range of 0.04-1.7% CO2. The concentration-response function describing the detectability of CO2 for the six rats was divided into an upper and lower limb at a concentration (5%) that was approximately equal to the end expiratory CO2 levels for the rat (4.88%). High levels of performance were observed for concentrations above this point, while those below it (0.02-2.5%) represented the dynamic range of detectability. Based on a 65% performance criterion, the average threshold performance for six rats was 0.52%. Possible interpretations of these data are discussed. PMID- 1901994 TI - Radioligand binding to adenosine receptors and adenosine uptake sites in different brain regions of normal and narcoleptic dogs. AB - The present study compares the characteristics of radioligand binding to adenosine receptors and adenosine uptake sites in 100- and 50-day-old normal and narcoleptic dogs. Binding to A1 receptors was quantified using a selective A1 agonist ([3H]N6-[(R)-1-methyl-2-phenylethyl] adenosine, [3H]R-PIA) and an antagonist ([3H]dipropyl-8-cyclopentyl-xanthine, [3H]CPX). Differences in the binding of [3H]R-PIA and that of [3H]5'-ethylcarboxamide adenosine ([3H]NECA), which binds to both A1 and A2 receptors with similar affinities, were used to quantify A2 receptors. Nucleoside transport sites were labeled with [3H]nitrobenzylthioinosine ([3H]NBTI), a potent inhibitor of nucleoside transport systems. The present study offered no evidence that either adenosine A1 receptors and adenosine uptake sites in the frontal cortex or adenosine A2 receptors in the putamen were altered in narcoleptic dogs. However, we found that adenosine A1 receptors in the dog exist in different affinity states and that the affinity state in which the receptor is found depends on the brain region examined. A characterization of these low- and high-affinity sites was performed and results indicated that these sites cannot be explained by a single interaction of the A1 receptor with a single G-protein population. PMID- 1901995 TI - Potentiation of spiperone-induced oral activity in rats after neonatal 6 hydroxydopamine. AB - The influence of central dopaminergic fibers on drug-induced oral activity in rats has not been well studied. Rats were treated 3 days after birth with bilateral intracerebroventricular 6-hydroxydopamine (6-OHDA; 134 micrograms total, base form) to destroy dopaminergic fibers in the brain. Control rats received vehicle by the same route. At about 10 weeks of age, a challenge dose of the dopamine D2 receptor antagonist, spiperone (40 micrograms/kg, IP), produced an 8-fold increase in the number of oral movements during a 60-minute observation period, vs. the control group. SKF 38393 (3.0 mg/kg, IP), a D1 agonist, produced the same number of oral movements as spiperone in the 6-OHDA group, representing a 2.4-fold increase over the controls. The Bmax and Kd for both D1 and D2 receptors was not changed in rat striatum by neonatal 6-OHDA treatment, even though dopamine content was reduced by 96%. These findings demonstrate that oral activity in rats can be greatly altered, even when there is no change in absolute numbers of D1 and D2 receptors and no change in the ratio of D1:D2 receptors. PMID- 1901997 TI - [Chemical mediators]. PMID- 1901998 TI - Pathogenic events during infection of the human nasopharynx with Neisseria meningitidis and Haemophilus influenzae. AB - The human nasopharynx is the natural habitat and reservoir for Neisseria meningitidis and Haemophilus influenzae type b (Hib). Meningococcal and Hib pathogenesis was studied in human nasopharyngeal tissue in organ culture. Inocula of greater than or equal to 10(6) meningococci or cfu of Hib were required for consistent production of infection in these cultures. By 24 hours meningococci and Hib grew to 10(8)-10(10) cfu/mL in culture supernatants, while 10(4)-10(7) cfu per organ culture were tissue associated. These studies further indicated that nasopharyngeal mucus contains components that specifically bind Hib; that both meningococci and Hib cause cytotoxicity, resulting in breakdown of tight junctions of epithelial cells, sloughing of ciliated cells, and ciliostasis; that pili are the most important components mediating initial attachment of meningococci to non-ciliated epithelial cells of the human nasopharynx; that Hib expresses both pilus and nonpilus adhesions that facilitate attachment to nonciliated cells; and that meningococci and Hib both invade the epithelial surface to reach the submucosa but do so by different routes. Meningococci and Hib have evolved successful, although divergent, mechanisms by which to infect the human nasopharynx. PMID- 1901999 TI - Parenteral antibiotic therapy for patients in nursing homes. AB - Since the number of aged Americans who require long-term care in nursing homes is increasing, attention has been focused on the cost-effective provision of medical care in the nursing home. In this health care setting, pneumonia and serious urinary tract infection are common among patients. These infections can now often be treated successfully with use of parenteral antibiotic therapy in the nursing home, thereby not subjecting the patient to the added stress of hospitalization. However, the physician's decision to use parenteral antibiotic therapy for the nursing home resident is complex and must be guided by the patient's condition, the wishes of the patient and family, the frequent shortage of professional staff, and the cost of the drug. Nevertheless, with these factors in mind, compassionate, high-quality care can often be provided in the nursing home in a cost-effective fashion. PMID- 1902000 TI - Activation of human T lymphocytes by Leishmania lipophosphoglycan. AB - This study describes Leishmania antigen-induced activation of lymphocytes isolated from Kenyan donors, previously treated for visceral leishmaniasis, and from Danish and Kenyan controls. Peripheral blood mononuclear cells (PBMC) from cured Kala-Azar patients proliferated and produced Interferon-gamma in vitro in response to lipophosphoglycan (LPG) isolated from Leishmania major. The proliferative response was mainly due to activation of CD2-positive T cells. PBMC from controls did not respond to LPG, but to sonicates prepared from both L. major and L. donovani promastigotes. The surface glycoprotein GP 63 failed to activate PBMC from any of the donors tested. These results show that the individuals cured from visceral leishmaniasis had expanded T-cell clones recognizing LPG, conceivably as a result of Leishmania infection. The LPG preparation was without detectable protein contamination. Thus, the results suggest that human T lymphocytes can respond to glycolipid antigens. PMID- 1902001 TI - Differential effects of interferon-gamma and low molecular weight BCGF on growth of human B lymphocytes; interferon-gamma prolongs the increased c-MYC mRNA levels after activation. AB - We have characterized the growth-stimulating effect of Interferon-gamma (IFN gamma) on various parameters of B cell growth, and compared the effects with those of low molecular weight B cell growth factor (lmw BCGF). We have found that IFN-gamma did not affect early changes induced by anti-mu, like initial calcium flux and rise in mRNA-and protein levels of the proto-oncogene c-myc measured at 3 h. On the other hand, IFN-gamma enhanced the effect of anti-mu on parameters measured later in the G1 phase of the cell cycle, such as expression of the transferrin receptor and general transcriptional activity, measured as an increase in 7-aminoactinomycin D binding. In particular, whereas the c-myc levels in anti-mu-treated cells peaked at 3 h and then gradually declined, IFN-gamma together with anti-mu maintained the c-myc levels at 24 h at approximately the same levels as seen at 3 h. Overall, lmw BCGF had a more potent effect on the parameters affected by IFN-gamma, correlating with stronger enhancement of DNA synthesis. However, in contrast to IFN-gamma lmw BCGF did not affect anti-mu induced c-myc mRNA levels. Thus this study has revealed differences between two B cell growth factors in effects on B cell cycle parameters. PMID- 1902002 TI - The effect of various contexts of stress on the mouse spleen lymphocytes and macrophage co-stimulatory activity. AB - Mice stressed daily by brief cold water immersions for 1, 8 or 14 days showed changes in immune system function which were dependent on the number of mice per cage, frequency of stress exposures and total number of stress exposures. Changed percentages of spleen B and CD4, but not of CD8 cells were determined when the mice were stressed either once or twice daily. With CD4 cells, increased percentages were seen after stress once daily but a decreased percentage was seen after stress twice daily. Furthermore, the Concanavalin A-stimulated spleen cell mitogenesis was decreased after 1 day of stress in mice stressed once daily as opposed to after 8 and 14 days of stress in mice stressed twice daily. After 14 days of stress, the lipopolysaccharide stimulated mitogenesis was increased if the mice were stressed once daily but decreased if the mice were stressed twice daily. With two mice per cage, we observed a decreased spleen cell mitogenesis after 14 days of stress. With four mice per cage, the spleen cell mitogenesis was decreased after 8 and 14 days of stress. If spleen cell populations from mice stressed twice daily for 8 days were depleted of macrophages and CD4 or CD8 cells, the effect of stress on the mitogenesis was removed from the CD8 cells. Spleen cells of mice stressed for 14 days showed a decreased mitogenesis when depleted of adherent cells and reconstituted with adherent cells from control mice. Furthermore, the adherent cells from these mice had decreased ability to support mitogenesis of adherent cell-depleted spleen cells from control mice as well as a decreased IL-1 production. PMID- 1902003 TI - [Veterinary medicine and molecular biology: possibilities and limits of virus detection]. AB - In the last years molecular biology has gained more and more influence in veterinary medicine, e.g. in animal breeding. In addition, methods of molecular biology may open new areas in the diagnosis of viral diseases, because they are fast and very sensitive. The following article displays an overview of molecular biological techniques that are currently in use for virus detection. In addition, the limits of these methods are discussed. In particular, the polymerase chain reaction (PCR) is described in some detail. Since this method has a considerable impact on the progress in molecular biology, it may as well be of importance for the detection of viruses. The potential of PCR in virus detection is illustrated using sheep and goat lentivirus and Bovine Viral Diarrhea/Mucosal Disease virus. PMID- 1902004 TI - In vitro activity of a new 'higher-lactam' antibacterial agent LY 193239. AB - In vitro activity of the new bicyclic pyrazolidinone LY 193239 (Eli Lilly) was evaluated against 52 clinical isolates of Haemophilus influenzae (4 were beta lactamase producers), 32 Enterococcus faecalis, 14 Neisseria gonorrhoeae (1 beta lactamase-positive) and 19 Neisseria meningitidis. Activity was best against Neisseria spp. and H. influenzae, including penicillinase-producing strains. Results of the time-kill study against a non-enzyme-mediated penicillin resistant strain of N. meningitidis indicate that exposure to an antibacterial concentration four times the minimal inhibitory concentration was bactericidal. E. faecalis was insensitive. PMID- 1902005 TI - The effects of tri-o-cresyl phosphate and metabolites on rat Sertoli cell function in primary culture. AB - A neurotoxic organophosphate, tri-o-cresyl phosphate (TOCP) is also a testicular toxicant. Histopathologic damage in the testis is first seen in Sertoli cells. TOCP and its activated metabolite saligenin cyclic-o-tolyl phosphate (SCOTP) were evaluated for effects on rat Sertoli cells in primary culture. SCOTP, but not TOCP, caused minor morphologic effects on the cells and increased levels of lactate in the spent medium with no change in pyruvate levels, synthesis of cellular or secreted proteins, or the cyclic AMP response to FSH stimulation. SCOTP was the metabolite of TOCP that produced the largest decrease in nonspecific esterase activity in Sertoli cells (up to 80%), when tested in the concentration range found in vivo. This decrease is consistent with previous in vivo evidence. These in vitro experiments replicate previously observed in vivo biochemical effects and suggest that SCOTP is the metabolite responsible for at least some of the biochemical effects seen in the testis after TOCP exposure. PMID- 1902006 TI - An investigation of the sensitivity of the ouabain-insensitive sodium efflux in single barnacle muscle fibers to pentachlorophenol. AB - The aim of the present work was to explore the possibility that pentachlorophenol (PCP) influences the behavior of the resting Na efflux in single muscle fibers from the barnacle, Balanus nubilus. It is shown here that PCP causes a transitory rise in the Na efflux in both unpoisoned and ouabain-poisoned fibers and that the response is dose-dependent, the minimal effective concentration in ouabain treated fibers being less than 10(-6) M. The efficacy of PCP is significantly greater than that of 2,3,4-trichlorophenol. 2,3-Dichlorophenol is ineffective. This is also the case with phenol. The magnitude of the response to PCP is a function of external pH. Lowering pHe increases the response. The response has an absolute requirement for external Ca2+ and is a sigmoidal function of external Ca2+ concentration. Since treatment of these fibers with PCP in high concentration leads to prompt contraction, experiments were designed to determine whether the observed rise in ouabain-insensitive Na efflux is due to a fall in myoplasmic pCa and whether trigger Ca2+ originates from the bathing medium. The results obtained show that prior injection of ethylene glycol bis(beta-aminoethyl ether) N,N'-tetraacetic acid (EGTA) or 1,2-bis(2-aminophenoxyethane-N,N,N',N' tetraacetic acid (BAPTA) leads to a drastic reduction in the response to PCP. They also show that prior external application of verapamil or devapamil stops the response to PCP from occurring. Both Cd2+ and Co2+ are also effective but only temporarily. Last, the effects of ryanodine and 8-(N,N-diethylamino)octyl 3,4,5-trimethoxybenzoate (TMB-8) were tested, since the former is known to block the sarcoplasmic reticulum Ca2+ release channel, and the latter to impair the action of agents known to release Ca2+ from internal depots. Both ryanodine and TMB-8 are found to reduce the response to PCP. Taken together, these observations support the hypothesis that PCP stimulates the ouabain-insensitive Na efflux by increasing the internal free Ca2+ and that the increase in internal Ca2+ is due to the entry of trigger Ca2+ from the outside via Ca2+ channels, as well as release of Ca2+ by the sarcoplasmic reticulum via its channel. They also indicate that the efficacy of PCP depends on the 5 Cl atoms present in its aromatic ring and pHe. PMID- 1902007 TI - Induction of cytochrome P450 and other drug metabolizing enzymes in rat liver following dietary exposure to Aroclor 1254. AB - Selected drug metabolizing activities were measured in female F344/NCr rats exposed to graded dietary concentrations of Aroclor 1254 (1 to 1000 ppm) for 7 days or to lower concentrations of Aroclor (1 to 10 ppm) for up to 28 days. Following the 7-day exposure, the hepatic O-dealkylation of ethoxyresorufin (ETR), mediated primarily by cytochrome P450IA, was increased 60-, 10-, and 4 fold by 33, 10, and 3 ppm Aroclor, respectively. In rats exposed to 10 and 3 ppm Aroclor for 28 days, this activity was increased approximately 30- and 10-fold, respectively. Hepatic ETR O-dealkylase activities correlated with Aroclor concentrations in the livers of exposed rats (r = 0.99, p less than 0.01). Although the O-dealkylation of benzyloxyresorufin was highly increased by 7-days dietary exposure to 1000 ppm Aroclor, the levels of Aroclor necessary for detection of induction were substantially higher than those required for detection of ETR O-dealkylase induction. Examination of the non-P450-mediated drug metabolizing activities, epoxide hydrolase and DT-diaphorase, similarly showed limited (approximately 10-fold) increases. In contrast, aldehyde dehydrogenase (benzaldehyde, NADP+) activity was highly increased (greater than 40-fold) at 1000 ppm, however this activity was increased to only a limited extent at lower Aroclor concentrations (e.g. approximately 3-fold at 33 ppm). These results support the potential use of cytochrome P450 activities as potential biomarkers for environmental exposure to PCBs and related compounds. PMID- 1902008 TI - The effects of thiamin on lead metabolism: whole body retention of lead-203. AB - The effects of thiamin on the whole body retention of led were evaluated in CD-1 mice treated intragastrically or intraperitoneally while exposed to a single dose of lead acetate (100 micrograms) containing 100 mu Ci lead-203. They were administered thiamin (25 or 50 mg/kg body wt.), calcium ethylenediamine tetraacetic acid (CaEDTA) (50 mg/kg body wt.) or their combination in pretreatment or posttreatment regimens for 13 days. Both pre- and posttreatment with thiamin reduced the lead retention compared to the untreated lead-exposed mice, although the different patterns of lead retention were observed. The combined pretreatment (thiamin 50 mg/kg and CaEDTA) and the CaEDTA treatment alone reduced the whole body retention of lead most effectively. Thiamin, CaEDTA and the combined treatments decreased the absorption of lead-203 and the biological half-life of retained lead-203 following oral or intraperitoneal lead exposure. The reduced absorption and enhanced excretion of lead associated with thiamin administration may have therapeutic application for the treatment of lead poisoning. PMID- 1902009 TI - Endocrine status in 29 patients treated by curative radiation therapy for nasopharyngeal carcinoma. AB - The basal endocrine status of 29 patients treated with curative radiation therapy for nasopharyngeal carcinoma was assessed; they were disease-free for a minimum of 4 years from the end of treatment. None showed clinical evidence of endocrine disease, and most of them had a substantially normal hormonal blood pattern. A slightly elevated TSH value, suggesting subclinical primary hypothyroidism, was found only in two male patients, which could be ascribed to the radiotherapeutic treatment of the neck. Although we cannot exclude more subtle alterations of hypothalamic-pituitary function, the percentage incidence of endocrine impairment in our patients seems lower than previously reported by other authors. PMID- 1902010 TI - Surgical treatment of concomitant urethral diverticulum and stress incontinence. AB - Urinary incontinence is frequently associated with a urethral diverticulum in female patients. Preoperative evaluation including a thorough history and physical examination, voiding cystourethrogram, urethroscopy, and urodynamic studies can diagnose both the urethral diverticulum and any concomitant bladder urethral dysfunction. Preoperative recognition of stress urinary incontinence or patients at risk for this problem postoperatively permits effective treatment with concomitant transvaginal bladder neck suspension and urethral diverticulectomy. PMID- 1902011 TI - Cerebral pathology in pseudoseizures. AB - Over a 5-year period 17% of admissions to an epilepsy unit in a psychiatric hospital had pseudoseizures; 42% of these patients also had concurrent epilepsy. Memory deficits were common both in those with pseudoseizures along (50%) and in those with concurrent epilepsy (62%). EEG abnormalities were more common in both groups with pseudoseizures than in a control group of patients with anxiety and affective disorders. Of specific EEG abnormalities only paroxysmal events occurred significantly more frequently in those with concurrent epilepsy than in those with pseudoseizures and in complicated cases of seizure disorder, the presence of cerebral pathology cannot be relied on to distinguish between epileptic and pseudo-seizures. PMID- 1902012 TI - Basal ganglia calcifications in postoperative hypoparathyroidism: a case with unusual characteristics. AB - A patient is described with post-thyroidectomy hypoparathyroidism and basal ganglia calcifications. The patient presented with a tonic-clonic seizure. The calcifications shown on CT scan were extensive in the basal ganglia, the bifrontal periventricular white matter and even in the brainstem. The white matter with calcifications displayed a high signal intensity on MRI, probably due to a different stage of the calcifying process in the white matter than in the basal ganglia. A severe dystonic reaction was observed after phenothiazine therapy and is discussed. PMID- 1902013 TI - The economic implications of radiologic screening for colonic cancer. PMID- 1902014 TI - Stones and infection in renal caliceal diverticula: treatment with percutaneous procedures. AB - Percutaneous treatment of symptomatic caliceal diverticula has expanded the application of uroradiologic intervention. To assess the safety and efficacy of these procedures, we have reviewed our experience with percutaneous management of 12 symptomatic caliceal diverticula, 10 with stones and two infected. Nine stone bearing diverticula were punctured directly with subsequent tract dilatation, nephroscopic stone extraction, and cavity obliteration (six with fulguration and drainage and three with drainage alone). One case was approached indirectly by puncturing a distant calix, dilating the diverticular neck, and flushing the stones into the collecting system for extraction. This cavity was not treated. Two infected diverticula were punctured directly for drainage and obliteration (one by fulguration and one by tetracycline sclerosis). Complete stone extractions were accomplished in all 10 cases. In eight with clinical follow-up ranging from 4 months to 6 years, one stone has recurred and seven patients are asymptomatic. Follow-up urograms were available in eight of 10 patients in whom cavity obliteration was attempted; in six (75%) of eight, nonvisualization of the diverticulum indicated successful obliteration. Only one major complication (urinoma requiring drainage) occurred. We conclude that percutaneous procedures are safe and effective in treating infected or stone-bearing caliceal diverticula. Direct diverticular puncture for access and diverticular fulguration for cavity obliteration is our preferred technique. PMID- 1902015 TI - Stable xenon CT cerebral blood flow imaging: rationale for and role in clinical decision making. AB - The stable xenon CT method of measuring cerebral blood flow has been investigated in research studies for over 10 years. Recently, it has been gaining clinical acceptance, primarily owing to a combination of several unique advantages it holds over other cerebral blood flow measurement techniques. The accuracy of this technique in quantifying low cerebral blood flow gives it a unique application in cases of brain death and acute stroke and it can be repeated after an interval of 20 min. making it possible to evaluate autoregulation and cerebrovascular reserve. Furthermore, cerebral blood flow information is directly coupled to CT anatomy. Although it is more difficult to administer than a standard CT scan, careful monitoring can ensure patient safety during the examination. In this article we review the physiologic and technical bases for the clinical application of xenon CT-derived quantitative cerebral blood flow information and discuss the advantages and disadvantages of the technique. We also describe its current clinical applications, including its usefulness in the evaluation of acute stroke, occlusive vascular disease, carotid occlusion testing, vasospasm, arteriovenous malformations, and head trauma management. PMID- 1902016 TI - Dyke Award. The search for human telencephalic ventriculofugal arteries. AB - Our study traced the vascular development of the fetal telencephalon in the last two trimesters of gestation and the first 15 years of life in 60 fetal and childhood brains. We filled the macro- and microvascular beds with Microfil and made stereoscopic observations of cleared 0.5- to 1.0-cm-thick sections. Separately, we identified developing vascular structures histologically. In our youngest specimen (16-weeks gestation), transcerebral channels with walls consisting of a single layer of endothelium and varying in diameter from 10 to 50 microns originated from leptomeningeal arteries and veins at right angles to the surface and passed through the cortical plate (future cortex). They branched at varying depths within the mantle and germinal matrix surrounding the lateral ventricles. At deeper levels the channels freely anastomosed with each other. A cortical microvascular network did not appear until 22 to 24 weeks. The new endothelial channels were derived from leptomeningeal vessels and from larger transcerebral channels. Most regions of isocortex developed a microvascular plexus simultaneously, regardless of degree of maturation. Striatal channels matured earlier than extrastriatal channels, having developed a muscularis to within 100 microns of the ganglionic eminence by 22- to 24-weeks gestation. Maturation of the vascular walls of extrastriatal channels into proper arteries and veins occurred during the first postnatal year. Anastomotic channels were present throughout the leptomeningeal, striatal, and extrastriatal regions in all of our specimens from 16 weeks gestation to 15 years old. Our study does not support the existence of ventriculofugal arteries and deep white matter arterial border zones in the human fetus and neonate, which have been postulated to be the basis of "periventricular" leukomalacia. PMID- 1902017 TI - The controversy of the periventricular white matter circulation: a review of the anatomic literature. PMID- 1902018 TI - Degenerative narrowing of the cervical spine neural foramina: evaluation with high-resolution 3DFT gradient-echo MR imaging. AB - Conventional two-dimensional Fourier transform (2DFT) MR evaluation of osteophytic disease of the cervical neural foramina is limited by section thickness, signal-to-noise problems, and CSF flow artifacts. We evaluated the role of thin-section, high-resolution, gradient-refocused three-dimensional Fourier transform (3DFT) MR imaging in assessing degenerative foraminal narrowing in the cervical spine. Contiguous 1.5-mm axial 3DFT gradient-recalled acquisition in the steady state MR images of 120 neural foramina at 60 disk levels were evaluated blindly and independently by three neuroradiologists. High-resolution axial CT was used as the gold standard in all patients. 3DFT MR was found to agree with CT in the detection of neural foraminal narrowing and in the determination of the cause of the narrowing in approximately 76% of neural foramina. The accuracy for the assessment of neural foraminal narrowing on 3DFT MR ranged from 73% to 82% when a 5 degrees-flip-angle, high-intensity CSF technique was used. When using the 30 degrees-flip-angle, low-intensity CSF technique, the accuracy ranged from 66% to 86%. When the cause of narrowing was evaluated, the 5 degrees and 30 degrees studies agreed with CT in 70-92% and 48 88% of the levels, respectively. When lesions were missed on MR, it was usually because of osteophytic disease. The interobserver concordance of MR and CT interpretations was higher for detecting the presence of narrowing than its cause. This MR technique is a useful method in the evaluation of foraminal stenosis since contrast between disk, cord, osteophyte, and CSF is high without the need for intrathecal injections.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1902019 TI - Effects of magnetic susceptibility artifacts and motion in evaluating the cervical neural foramina on 3DFT gradient-echo MR imaging. AB - The purpose of this study was to evaluate in vitro the effects of magnetic susceptibility and motion on the estimation of neural foraminal diameter with three-dimensional Fourier transformation (3DFT) gradient-recalled MR imaging as compared with CT. A cervical spine phantom was constructed from desiccated human cervical vertebral bodies embedded in a water-based proteinaceous gel. The phantom was imaged with thin-section 1.5-mm axial CT and 1.5-mm axial 3DFT gradient-recalled MR using a constant TR (35 msec) and flip angle (5 degrees), while the TE was varied from 11 to 22 msec. During imaging, the phantom either was kept stationary or underwent subtle, intermittent motion. Compared with CT, MR consistently underestimated the diameters of the neural foramina, leading to overestimation of neural foraminal stenosis. The degree of over-estimation varied directly with increasing TE values, from 8% (TE = 11 msec) to 27% (TE = 22 msec). Motion artifacts also increased foraminal overestimation and mimicked osseous hypertrophy. The effect of image degradation due to motion was noted to increase with longer TE values. Image degradation caused by magnetic susceptibility and motion artifacts can be minimized by using the shortest TE possible. We do not recommend the use of 3DFT gradient-recalled MR imaging for the evaluation of cervical radiculopathy if patient motion is anticipated. PMID- 1902020 TI - An epidural cavernous hemangioma of the spine. PMID- 1902021 TI - Intra- and paraorbital lesions: value of fat-suppression MR imaging with paramagnetic contrast enhancement. AB - The orbital area of 18 individuals was examined by using a combination of fat suppression contrast-enhanced MR imaging to determine whether contrast between fat and surrounding tissues could be improved over that obtained with conventional fat-suppression techniques alone. We used a hybrid technique combining two independent methods of fat suppression. Subjects consisted of 16 patients and two normal volunteers. Fifteen individuals received gadopentetate dimeglumine, and conventional T1-weighted, T2-weighted, and fat-suppression T1 weighted images were obtained. The fat-suppressed T1-weighted images obtained after contrast administration provided more information than did the conventional MR images. Intraorbital and paraorbital lesions could be distinguished easily from intraorbital fat that had been suppressed. Cases of chorioretinitis and optic neuritis could be confidently diagnosed only by this technique. Cases of optic nerve meningioma and mixed conal lesions also were better appreciated. Because of sharp contrast between tissue planes, this technique was helpful for detecting any intraorbital invasion from paraorbital lesions. Fat-suppression MR imaging with paramagnetic contrast enhancement can significantly improve the delineation of both normal and abnormal structures and better define lesional margins in the orbit, where large amounts of fat are present. Our results support earlier findings, and we suggest that postcontrast fat-suppressed T1-weighted imaging be used instead of conventional T1-weighted postcontrast imaging in evaluating orbital and paraorbital lesions. PMID- 1902022 TI - Orbital granulocytic sarcoma. PMID- 1902023 TI - Granulocytic sarcoma (chloroma): sphenoidal sinus and paraspinal involvement as evaluated by CT and MR. PMID- 1902024 TI - Granulocytic sarcoma. PMID- 1902025 TI - Nasopharyngeal carcinoma: CT evaluation of patterns of tumor spread. AB - In a prospective study using CT as the initial means of radiologic evaluation in 262 patients with proved nasopharyngeal carcinoma, the paranasopharyngeal space was found to be the most commonly involved region (84.4%), both uni- and bilaterally. Unilateral involvement was found in 44.3% of patients (116/262) and bilateral involvement in 40.1% (105/262). The other structures or regions that were involved, in decreasing order of frequency, were the sphenoid sinus (26.7%), nasal fossa (21.8%), and ethmoid sinus (18.3%). Erosion of the base of the skull and intracranial intracranial extension into the middle cranial fossa were common (31.3% and 12.2%, respectively). The primary tumor in the nasopharynx was found to be contiguous with metastatic upper cervical nodes through paranasopharyngeal extension of tumor in 35 patients (13.4%). A qualitative method to assess the degree of paranasopharyngeal extension is proposed. The extent of paranasopharyngeal extension so evaluated was correlated with other attributes of tumor extent (p = .0001), namely, nasal or oropharyngeal extension, which constitutes a T3-level tumor, and erosion of the base of the skull or orbit, which constitutes a T4-level tumor. The extent of paranasopharyngeal extension was also correlated with local control of the tumors (p = .0001). At a median follow-up of 27 months, only three (7.9%) of the 38 patients with no paranasopharyngeal extension had nasopharyngeal relapse, while 12 (11.2%) of the 107 and 17 (34.7%) of the 49 patients with types 1 and 2 paranasopharyngeal extension, respectively, had nasopharyngeal relapse.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1902026 TI - Benign lymphoepithelial parotid tumors in AIDS patients: CT and MR findings in nine cases. AB - Benign lymphoepithelial parotid neoplasm with associated cervical adenopathy is a newly described head and neck manifestation of HIV infection, characterized previously as purely cystic masses on both CT and MR evaluations. The CT and MR findings in nine cases of surgically proved benign lymphoepithelial parotid lesions are presented. Five (56%) of the nine cases demonstrated masses that appeared other than cystic, reflecting a greater variety of radiologic appearances than previously reported. The majority of these cystic masses contained solid components and therefore could not be labeled as cysts; instead, they were considered to be benign lymphoepithelial parotid lesions. For patients with parotid gland enlargement, the lack of a characteristic CT/MR appearance of these lesions necessitates an evaluation of clinical history and a determination of whether cervical adenopathy is present in order to determine their underlying origin. PMID- 1902027 TI - CT evidence of mucosal thickening in the maxillary antra in patients with nasopharyngeal carcinoma. AB - CT scans of the maxillary antra in a group of 51 patients with nasopharyngeal carcinoma were compared with those of a control group of 50 patients. Inflammatory thickening of the antral mucosa was demonstrated in 39 of 42 patients with grade WHO (World Health Organization) 2 and 3 nasopharyngeal carcinoma. Biopsy of the antral mucosa in eight of these patients established inflammation and excluded the presence of nasopharyngeal carcinoma in the antrum. In a group of nine patients with WHO 1 tumors, the antral mucosa was normal. Thickening of the antral mucosa was observed in six patients of the control group. The inflammatory thickening of the antral mucosa in the patients with WHO 2 and 3 tumors was obviously more frequent than in the control group. This combination was not found in patients with WHO 1 tumors. The phenomenon cannot be explained by direct extension of nasopharyngeal carcinoma or obstruction of the maxillary osteum. The cause of the mucosal thickening may be immunologic, but remains unclear at this stage. The high frequency of inflammatory thickening of the antral mucosa observed in patients with WHO 2 and 3 tumors should encourage further investigation of causative factors in nasopharyngeal carcinoma. PMID- 1902028 TI - Metallic otologic implants: in vitro assessment of ferromagnetism at 1.5 T. AB - MR imaging is contraindicated for patients with certain ferromagnetic implants because of potential risks related to movement or dislodgement. This is especially true for metallic implants located in sensitive areas of the body, such as those placed in and around the ear. Therefore, the ferromagnetic qualities of 35 different metallic otologic implants were assessed by placing them individually on a millimeter scale in a plastic petri dish that was slowly moved into the center of a 1.5-T MR imaging system. None of the metallic otologic implants moved during this procedure. The results demonstrate that each of these implants are made from nonferromagnetic materials and do not pose a risk to patients undergoing high-field-strength MR imaging. These data effectively expand the list of metallic implants that appear to be safe for MR imaging. PMID- 1902029 TI - Intracranial cryptococcosis in immunocompromised patients: CT and MR findings in 29 cases. AB - CT and MR scans of 29 immunocompromised patients (28 with AIDS or ARC, one with diabetes mellitus) who had documented intracranial cryptococcal infection were reviewed retrospectively. All patients had CT studies; 26 received iodinated contrast agent. CT findings included normal results in nine of 29, atrophy only in 13 of 29, nonenhancing lesions in three of 29, enhancing lesions in two of 20, and foci of leptomeningeal calcification in two of 29. Ten patients had both CT and MR studies, and four received gadopentetate dimeglumine. Among these 10 patients, five had normal CT studies and one showed moderate central atrophy. All 10, however, had abnormal MR findings. We observed four patterns: (1) parenchymal cryptococcoma (3/10); (2) numerous clustered tiny foci that were hyperintense on T2-weighted images and non-enhancing on postcontrast T1-weighted images, located relatively symmetrically in the basal ganglia bilaterally and in midbrain, representing dilated Virchow-Robin spaces (4/10); (3) multiple miliary enhancing parenchymal and leptomeningeal nodules (1/10); and (4) a mixed pattern, consisting of dilated Virchow-Robin spaces with mixed lesions such as cryptococcoma and miliary nodules (2/10). In the group of six patients with dilated Virchow-Robin spaces (patterns 2 and 4), two received gadopentetate dimeglumine, but the Virchow-Robin space lesions did not enhance; among the remaining four patients, two received gadopentetate dimeglumine (one with pattern 1 and one with pattern 3) and the lesions did enhance. Three patients in our study subsequently died and autopsies were performed. The postmortem results revealed dilated Virchow-Robin spaces filled with fungi in the basal ganglia, which correlated well with MR findings.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1902030 TI - Disseminated CNS histoplasmosis. PMID- 1902031 TI - Diagnosis of cerebral metastases: double-dose delayed CT vs contrast-enhanced MR imaging. AB - For patients suspected of having cerebral metastases, double-dose delayed CT (DDD CT) has proved significantly more sensitive than CT scans obtained immediately after administration of a lesser dose of iodinated contrast material. Previous reports confirm the advantages of postcontrast MR imaging over contrast-enhanced CT, but data comparing DDD-CT and contrast-enhanced MR have not been reported. This study describes comparative imaging results in 23 patients who had contrast enhanced MR imaging to clarify equivocal findings on DDD-CT studies. Contrast enhanced MR demonstrated more than 67 definite or typical parenchymal metastases. T2-weighted MR revealed more than 40, while DDD-CT revealed only 37 typical metastatic lesions. Three patients had five or fewer lesions on DDD-CT and lesions "too numerous to count" on MR. The frequency of equivocal or unconvincing lesions was similar on DDD-CT (11) and contrast-enhanced MR (10). On T2-weighted images, we noted a substantially higher number of equivocal lesions (19), fewer definite metastases, and a number of definite metastases that had no corresponding lesion on the enhanced studies, confirming the inability of T2 weighted imaging to specifically identify cerebral metastases. In one case, multiple tiny lesions on T2-weighted images were not apparent on DDD-CT scans and were recognized only in retrospect on contrast-enhanced MR images. In this series, MR with enhancement proved superior to DDD-CT for lesion detection, anatomic localization of lesions, and differentiation of solitary vs multiple lesions. Cost-benefit considerations precluded a comparison between the two techniques in all patients suspected of having cerebral metastases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1902032 TI - Gadopentetate dimeglumine-enhanced MR imaging in children following surgery for brain tumor: spectrum of meningeal findings. AB - Gadopentetate dimeglumine-enhanced MR imaging was performed in 51 consecutive postoperative pediatric neurosurgical patients with a diagnosis of brain tumor. These studies were examined retrospectively to determine the spectrum of meningeal findings in this patient population. Patterns of enhancement were correlated with type of surgery, interval since surgery, clinical and CSF findings, and the use of radiation and steroid therapies. Normal postoperative meningeal findings include no meningeal enhancement or mild focal or diffuse dural enhancement. More moderate dural or subdural enhancement may be seen in clinically well children who have postsurgical subdural collections, or who have a remote history of serious meningeal disease (meningitis or subarachnoid hemorrhage). In all six cases in which nodular dural, leptomeningeal, or ependymal enhancement was seen, recurrent local tumor, leptomeningeal metastases, or infection were present. Leptomeningeal tumor or infection should be suspected if such patterns of enhancement are noted. Parameters that did not appear to affect the pattern of meningeal enhancement included type of surgery, interval since surgery, or therapeutic radiation. PMID- 1902033 TI - Hamartomas of the tuber cinereum: CT, MR, and pathologic findings. AB - The neuroimaging studies, clinical evaluations, and surgical and pathologic findings in five children with biopsy-proved hamartomas of the tuber cinereum were reviewed. Surgical and/or MR findings showed that patients with precocious puberty had pedunculated lesions while those with seizures had tumors that were sessile with respect to the hypothalamus. The radiologic studies included six MR examinations in four patients and CT studies in all five patients. Three children presented with precocious puberty and two with seizures, one of which was a gelastic (spasmodic or hysteric laughter) type of epilepsy. MR studies were obtained both before and after surgery in two patients, only preoperatively in a third patient, and only postoperatively in the fourth child. MR was superior to CT in displaying the exact size and anatomic location of the hamartomas in all cases. The mass was isointense with gray matter on sagittal and coronal T1 weighted images, which best displayed the relationship of the hamartoma to the third ventricle, infundibulum, and mammillary bodies. Intermediate- or T2 weighted images showed signal characteristics of the hamartoma to be isointense (one case) or hyperintense (two cases) relative to gray matter. The difference in T2 signal intensity did not correlate with any obvious differences in histopathology. CT showed attenuation isodense with gray matter, and no calcium. There was no enhancement on CT. There was no enhancement on MR in the one case in which contrast medium was administered. Preservation of the posterior pituitary bright spot was noted on all pre- and postoperative T1-weighted MR scans.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1902034 TI - CT and MR of meningeal melanocytoma. PMID- 1902035 TI - Dense dermoid cyst of the posterior fossa. PMID- 1902036 TI - Management of vascular perforations that occur during neurointerventional procedures. AB - This article describes a number of treatment strategies for the management of perforations that occur during neurointerventional procedures. During the past 5 years, we have performed over 1200 endovascular procedures to treat vascular disorders involving the brain and spinal cord (400 cerebral arteriovenous malformations, 230 tumors, 197 carotid cavernous fistulas, 183 aneurysms, 130 dural fistulas, 80 spinal arteriovenous malformations, 18 vein of Galen aneurysms, and 20 cases of vasospasm). Fifteen patients (1.1%) sustained a vascular perforation as a direct result of these procedures. Among these 15 patients, indications for endovascular treatment were six symptomatic arteriovenous malformations, two spinal cord arteriovenous malformations, two cavernous sinus dural fistulas, one transverse sinus fistula, one case of vasospasm following subarachnoid hemorrhage, one direct carotid cavernous fistula, one vein of Galen malformation, and one ruptured basilar artery aneurysm. The vascular perforations were grouped into three probable mechanisms: mechanical perforation of a normal vessel (six patients), mechanical disruption of a dysplastic vessel or aneurysm (five patients), and fluid overinjection (four patients). Treatment of the perforations included immediate reversal of anticoagulants (12 patients) and direct closure of the perforation site with coils (five patients). In addition, closure of the intravascular compartment adjacent to the perforation was achieved with coils (six patients), liquid adhesives (four patients), balloons (two patients), or particles (two patients). In two patients a detachable balloon was placed transiently across the perforation site for several minutes, deflated, and removed when no further extravasation was noted. Five patients were started on anticonvulsant therapy, two of whom have had a new onset seizure related to the perforation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1902037 TI - A solution that simulates whole blood in a model of the cerebral circulation. PMID- 1902038 TI - Clinical manifestations of hydrocephalus caused by impingement of the corpus callosum on the falx: an MR study in 40 patients. AB - The clinical features of patients with hydrocephalus include generalized reductions in coordinated motor and cognitive functions. Although some group similarities have been noted, the outward manifestations of this dysfunction vary in degree and character, with some subjects revealing no overt signs of the underlying hydrocephalus. A retrospective review of subjects with MR criteria of hydrocephalus was undertaken to reevaluate the specific imaging correlates of the signs and symptoms associated with this pathologic process. Forty adults with hydrocephalus on MR evaluation were carefully scrutinized in an effort to elucidate specific clinicoradiologic patterns of abnormality. Spin-echo MR techniques were used with T1 and/or T2 weighting in three orthogonal planes. MR criteria of hydrocephalus encompassed dilated lateral ventricles to include the temporal horns, a pronounced upward elevation of the corpus callosum, and an outward expansion of the cerebral hemispheres at the expense of the subarachnoid space overlying the convexities. The significant related morphologic change on MR that has not been previously described in hydrocephalus was a localized dorsal flattening and thinning of the posterior body of the corpus callosum. Importantly, all but three of the 24 patients with this phenomenon manifested varying combinations of imbalance, gait disturbance, incontinence, short-term memory deficits, and global dementia. In the presence of hydrocephalus, but in the absence of this specific callosal configuration, only one of the remaining 16 subjects revealed symptoms that might suggest the presence of hydrocephalus (i.e., profound dementia). The structure responsible for this focal callosal flattening and thinning in hydrocephalus is the rigid free surface of the falx cerebri as it impinges on the caudal extent of the upwardly expanding corpus callosum and supracallosal hippocampal formation. This mechanical insult hypothetically causes variable axonal dysfunction, ranging from decreased to increased neurophysiologic activity. In summary, it is postulated that callosal impingement represents a dynamic partial hemispheric disconnection and accounts, in part, for the complex clinical state associated with hydrocephalus. PMID- 1902039 TI - Contrast-enhanced CT of acute isodense subdural hematoma. PMID- 1902040 TI - Disseminated intravascular coagulation and the neuroradiologist. PMID- 1902041 TI - Epidural pneumatosis: a benign entity in trauma patients. PMID- 1902042 TI - Vein of Galen malformation: correlation of clinical presentation, arteriography, and MR imaging. AB - To test the value of currently proposed angiographic categorizations of vein of Galen malformations and a hypothesis regarding the causes of vein of Galen malformations and of accompanying hydrocephalus, as well as to assess the relative utility of MR imaging and CT in clinical evaluation, we reviewed the clinical and radiologic records of 34 patients with vein of Galen malformations. Patients were divided into two groups on the basis of the angiographic demonstration of either an arteriovenous malformation nidus or a direct arteriovenous fistula to the wall of the vein of Galen or one of its tributaries. Patients with such a nidus (n = 17) could be distinguished from those with arteriovenous fistulas alone (n = 17) on the basis of age at presentation (p less than .01) and presenting symptoms. Venous constraints, thought to be etiologically important, were identified in 31 of 34 patients. The presence or absence of hydrocephalus was explainable by mass effect in only 24 of 32 patients. In seven of 32 cases, no obvious mass effect was seen in the presence of hydrocephalus, but arteriographic evidence of venous hypertension was present in all patients with hydrocephalus. MR provided improved depiction of both arterial and venous anatomy as compared with CT. Parenchymal abnormalities were uncommon. No patients had subarachnoid hemorrhages. We conclude that MR is superior to CT in the clinical evaluation of vein of Galen malformations, that the angiographic finding of a nidus separates patients with vein of Galen malformations into clinical and therapeutically relevant groups, and that simple mass effect on the aqueduct is not an adequate explanation for all cases of hydrocephalus in patients with this disease. PMID- 1902043 TI - Paradoxical cerebral emboli associated with pulmonary arteriovenous shunts: report of three cases. AB - Paradoxical embolism to the cerebral circulation is rarely diagnosed in life; however, three such cases have recently been observed: two with multiple congenital pulmonary arteriovenous malformations and one with an acquired arteriovenous fistula. In each case the pulmonary lesion(s) were treated by percutaneous balloon embolizations. Paradoxical embolism should be included in the differential diagnosis of cerebral arterial embolism for which there is no obvious source, especially when there is also evidence of concurrent peripheral venous thrombosis and/or pulmonary embolism. PMID- 1902044 TI - Chemical-shift imaging of a spontaneous internal carotid artery dissection: case report. PMID- 1902045 TI - Cranial MR imaging in rhizomelic chondrodysplasia punctata. PMID- 1902046 TI - Cystic intraparenchymal meningioma in a child: case report. PMID- 1902047 TI - Technical note: sonography through the posterior fontanelle in diagnosing neonatal intraventricular hemorrhage. PMID- 1902048 TI - MR measurement of intracranial CSF volume in 41 elderly normal volunteers. AB - A noninvasive nonplanimetric MR protocol was used to measure the total intracranial CSF volume in 41 normal subjects, aged 60-84 years, who were intensively screened to eliminate CNS disease. The protocol entailed application of MR imaging data acquired with a spin-echo sequence in a single thick slice encompassing the head. The results show a strong correlation between increased intracranial CSF volume and increasing age, and a weaker correlation between increased intracranial CSF volume and increasing total intracranial volume. The possibility of employing a CSF volume measurement as a reflection of brain atrophy to help diagnose dementia is discussed. PMID- 1902049 TI - MR demonstration of leukoencephalopathy associated with mitochondrial encephalomyopathy: case report. PMID- 1902050 TI - Contrast-enhanced MR imaging of neurocutaneous melanosis. PMID- 1902051 TI - Effect of nitroglycerin on coronary collateral function during exercise evaluated by quantitative analysis of thallium-201 single photon emission computed tomography. AB - A noninfarcted, entirely collateral-dependent myocardial region provides an opportunity to assess the effect of nitroglycerin on coronary collateral function during exercise. Stress thallium-201 computed tomography was performed in seven patients with effort angina and no history of myocardial infarction, both before and after nitroglycerin (0.3 mg). All patients had single-vessel disease with total or subtotal (99% with delay) occlusion of proximal left anterior descending coronary artery and well-developed collaterals. The pressure-rate product, mean blood pressure, and heart rate at peak exercise did not differ before and after nitroglycerin. The size of the perfusion defect and the severity of ischemia during exercise estimated by quantitative analysis of thallium-201 single photon emission computed tomography were significantly less after nitroglycerin administration (extent score: 23 +/- 17 vs 7 +/- 9, p less than 0.01; severity score: 20 +/- 22 vs 3 +/- 4, p less than 0.05). The pressure-rate products at peak exercise did not differ before and after nitroglycerin, which suggested that the reduction in perfusion defect size was unlikely to be the result of decreased myocardial oxygen consumption. These results suggest that nitroglycerin improved coronary collateral function during exercise and thus prevented exercise-induced myocardial ischemia. PMID- 1902052 TI - The effect of enteric-coated aspirin on the morning increase in platelet activity. AB - In vitro platelet aggregability to adenosine diphosphate (ADP) and epinephrine increases in the morning, as does the frequency of myocardial infarction. A single-blind, randomized, cross-over study of 15 healthy males was conducted to determine: (1) if other measures of platelet activity show a morning increases and (2) if aspirin eliminates any increases in platelet activity detected. Subjects received 325 mg of enteric-coated aspirin (ECA) or placebo. During placebo therapy,platelet thromboxane A2 production (following collagen stimulation) increased significantly after the subjects got up, as did platelet aggregability to ADP, epinephrine, and collagen. ECA markedly reduced baseline platelet thromboxane A2 production and eliminated the increase after the subjects got up. It also abolished biphasic aggregation in response to epinephrine and ADP (thereby eliminating the morning increase in aggregability to these agents), lengthened collagen lag time, reduced synergistic aggregation to combined agonists, was effective on day 2, and did not alter increases of tissue plasminogen activator that occurred following the subjects' arising. If aspirin prevents myocardial infarction by its antiplatelet action, as seems likely, the preferential reduction of morning infarction observed in the Physicians' Health Study, and the demonstration that aspirin eliminates the morning increase in platelet activity, suggest that the morning increase in myocardial infarction is due in part to a concurrent relatively modest increase in platelet activity. PMID- 1902053 TI - The effect of nitroglycerin on pulmonary vascular capacitance in dogs. AB - In this study we investigated the hypothesis that the decrease in pulmonary vascular pressures observed after administration of nitroglycerin is in part due to a shift in the pulmonary vascular pressure-volume relationship. The experiments were done in six closed-chest dogs anesthetized with pentobarbital, in which pulmonary, cardiac, and intestinal relative blood volumes were determined by equilibrium blood pool scintigraphy. Nitroglycerin (30 micrograms/kg/min) caused 7% (p less than 0.02) and 12% (p less than 0.02) reductions in pulmonary and total cardiac blood volume, respectively, and a 7% (p less than 0.01) increase in intestinal blood volume. This shift of blood from the heart and the pulmonary circulation to the systemic (intestinal) circulation was accompanied by reductions in mean pulmonary artery pressure from 16 +/- 2 mm Hg to 12 +/- 1 mm Hg (p less than 0.01), in mean pulmonary capillary wedge pressure from 11 +/- 2 mm Hg to 6 +/- 1 mm Hg (p less than 0.01), and in mean portal pressure from 9 +/- 1 mm Hg to 8 +/- 1 mm Hg (p less than 0.01). The position of the pulmonary vascular pressure-blood volume relationship was unaffected by nitroglycerin, whereas the portal pressure-intestinal blood volume relationship was shifted to the left and upward. These changes suggest that pulmonary vascular tone remained unchanged, whereas intestinal vascular tone decreased during administration of nitroglycerin. In conclusion, nitroglycerin decreased pulmonary vascular pressures through a passive emptying of the pulmonary circulation as a result of increased systemic (intestinal) vascular capacitance. PMID- 1902054 TI - Comparison of effects of thrombolytic therapy on left ventricular function in patients over with those under 60 years of age. AB - This study examined the effect of age on left ventricular (LV) function, assessed by contrast ventriculography 3 weeks after a first acute myocardial infarction in 312 patients who received thrombolytic therapy within 4 hours of the onset of infarction and in 83 patients who received placebo. Streptokinase was given to 188 patients and recombinant tissue-type plasminogen activator (rt-PA) to 124. Patients were divided into 2 age groups: less than 60 years (n = 244) and greater than or equal to 60 years (n = 151). Thrombolytic therapy improved ejection fraction in both age groups: from 54 +/- 13 to 59 +/- 11% (p = 0.021) in the younger group and from 50 +/- 14 to 57 +/- 13% (p = 0.004) in the older group. Ejection fraction was identical in streptokinase- and rt-PA-treated patients. Multifactor analysis of variance revealed that younger age and thrombolytic therapy were independently associated with improved ejection fraction. Thrombolytic therapy also reduced end-systolic volume (p = 0.001) by 14 ml in the elderly and 9 ml in the younger group. Minor bleeding complications were more frequent in the elderly and 3 serious hemorrhages occurred in patients greater than or equal to 60 years. These findings reveal that thrombolysis improves LV function in all age groups studied. Because increasing age is independently associated with a lower ejection fraction after acute myocardial infarction, thrombolytic therapy may confer greater benefits in older patients. PMID- 1902055 TI - Mortality in patients treated with flecainide and encainide for supraventricular arrhythmias. AB - In a recent clinical trial, the class Ic antiarrhythmic drugs encainide and flecainide were found to be associated with an increased mortality risk in patients with new myocardial infarction and ventricular arrhythmias. The purpose of this study was to assess whether an increased mortality risk also accompanied the use of these drugs to treat patients with supraventricular arrhythmias. Data were obtained from the respective pharmaceutical sponsors on the mortality observed with each drug in United States and foreign protocols enrolling patients with supraventricular arrhythmias. Mortality in the encainide population (343 patients) and the flecainide population (236 patients) was compared with that in a research arrhythmia clinic, the Duke population (154 patients). Nine deaths occurred in the combined encainide-flecainide population and 10 deaths occurred in the Duke population; the follow-up periods averaged 488 days and 1,285 days, respectively. The 6-year survival functions of these 2 populations, estimated by the Kaplan-Meier technique, did not differ significantly (p = 0.62). The hazard ratio for the combined encainide-flecainide population relative to the Duke population was estimated to be 0.6 with a 95% confidence interval of 0.2, 1.7. These descriptive comparisons did not demonstrate any excess mortality when flecainide and encainide were used in patients with supraventricular arrhythmias. PMID- 1902056 TI - Chagas' disease: risk factors for house infestation by Triatoma dimidiata, the major vector of Trypanosoma cruzi in Costa Rica. AB - The reduction of domiciliary infestation by insect vectors, the key to controlling Chagas' disease, depends on identification of housing features associated with infestation. In this study, log-linear modeling was used to reanalyze data collected in 1964-1968 from 371 houses on characteristics potentially associated with infestation by the vector Triatoma dimidiata in a Costa Rican town with endemic Chagas' disease. A possible increased risk of infestation was observed for houses with a dirt floor (as compared with houses with another floor type) and for houses in poor sanitary condition (as compared with houses in good sanitary condition). A new risk factor for house infestation, the presence of roof tiles, was identified; the odds of infestation for houses with a tile roof were 2.4 times greater than the odds for houses with a galvanized metal roof. This significantly increased risk is probably due to the harboring of T. dimidiata in stacks of spare tiles next to house walls rather than to the tile roofs themselves. PMID- 1902057 TI - Structure of the chromosomal gene and cDNAs coding for lactase-phlorizin hydrolase in humans with adult-type hypolactasia or persistence of lactase. AB - Lactase-phlorizin hydrolase (LPH) splits lactose in the small intestine. LPH activity is high in the suckling; in many human populations the activity declines in adults, leading to adult-type hypolactasia, whereas in other populations the high LPH activity persists in adults. In the present work, we compared LPH sequences at the gene and cDNA level among adult subjects with high and low LPH activity. The complete intron-exon organization, including the sequences of all 17 exons and of the borders of all introns (as well as about 1,000 bp of 5' flanking region), was established for the cloned chromosomal LPH gene of a subject with persistence of lactase. Using PCR, we directly sequenced the exons of a hypolactasic subject. Except for silent mutations and the unknown linkage phase at two heterozygous positions, both coding sequences were identical. We further examined the LPH mRNA of a hypolactasic subject by S1 mapping and by sequencing a set of overlapping PCR products produced from cDNA templates. Except for allelic differences, the LPH sequence of the hypolactasic subject was identical to that of the LPH cDNAs of three subjects with persistence of lactase (one cDNA isolated previously by cloning and two characterized in the present work by PCR). No allele was peculiar to the hypolactasic subject. We conclude that humans with high or low levels of lactase can code for identical LPH enzymes. PMID- 1902059 TI - Polymorphic aspects of male anthropoid canines. AB - Interspecific variation in the architecture of male anthropoid maxillary canines is documented. Extant taxa are polymorphic, and most can be sorted into two major groupings based on quantitative measures of shape, distal edge sharpness, and interspecific changes in their linear dimensions (projection, mesiodistal length, and buccolingual breadth) relative to each other and to body mass (scaling). One group includes the great apes and ceboids; the other includes cercopithecoids and hylobatids. Statistically significant differences between these groups were found for canine shape, for trajectories of regressions for canine projection on canine length and canine breadth, and for canine projection and canine breadth relative to body mass. The data indicate that explantations of canine variation in male anthropoids must include a mechanical interpretation of form in addition to assessments of habitus, heritage, and body mass. PMID- 1902058 TI - Evidence for the segregation of a major gene in human susceptibility/resistance to infection by Schistosoma mansoni. AB - Severe clinical disease caused by the major human parasite Schistosoma mansoni is the consequence of high and prolonged infections. Epidemiological studies indicate that, for individuals having frequent contacts with cercaria-infested waters, both infection intensities and reinfection after treatment depend, in large part, on their intrinsic susceptibility/resistance to infection, suggesting the role of genetic factors in human resistance to S. mansoni. To investigate whether a major gene controls human susceptibility/resistance to infection by S. mansoni, segregation analysis of infection intensities, adjusted for the factors relevant in schistosomiasis (water contact, age, sex), was performed on 20 Brazilian pedigrees (269 individuals), using both the unified mixed model and the regressive model of analysis. The results are consistent with the hypothesis that there is a codominant major gene controlling human susceptibility/resistance to infection by S. mansoni. Parameter estimates indicate a frequency of .20-.25 for the deleterious allele; thus, about 5% of the population is predisposed to high infections, 60% is resistant, and 35% has an intermediate, although fairly good, level of resistance. These findings provide a genetic basis for earlier observations on the lower resistance and the predisposition to reinfection of certain individuals. In addition to the detection of a major gene effect, the data suggest that immunity to S. mansoni develops progressively during childhood to reach a maximum around the age of puberty. The implications of these results for the strategy to be used in endemic areas to reduce morbidity and to control parasite transmission are discussed. PMID- 1902060 TI - Urea transport deficiency in Jk(a-b-) erythrocytes. AB - The activity of the urea transporter was determined in human erythrocytes of the Kidd blood type Jk(a-b-) by measuring unidirectional urea and thiourea fluxes in tracer flux experiments and urea net fluxes in light-scattering experiments. When compared with control cells, Jk(a-b-) cells exhibited diminished urea and thiourea fluxes and lacked the kinetic characteristics of mediated transport, suggesting that in these cells urea and thiourea moved only by simple diffusion through the lipid bilayer. Control experiments showed that anion, water, and ethylene glycol permeabilities were the same in Jk(a-b-) and control cells. These experiments thus demonstrate that Jk(a-b-) cells lack mediated urea transport and strongly support the notion that urea transport function is separate from the transport for anions, water, and ethylene glycol, probably because different proteins are responsible for these transport functions. PMID- 1902061 TI - Role of calcium in dopaminergic regulation of TRH- and angiotensin II-stimulated prolactin release. AB - The contributions of intracellular and extracellular calcium to thyrotropin releasing hormone (TRH)- and angiotensin II (ANG II)-stimulated prolactin (PRL) release and the role of calcium in dopaminergic inhibition of these events were examined because of unresolved controversies in these areas. Dispersed normal female rat anterior pituitary cells were used to evaluate radiocalcium fluxes and the intracellular calcium concentration ([Ca]i). Both peptides increased PRL release, fractional 45Ca2+ efflux, and [Ca]i in a spike and plateau pattern, and neither increased 45Ca2+ uptake. In a low-calcium buffer, TRH and ANG II stimulated less than 5% of the normal PRL response, yet efflux was at least 50% of normal and [Ca]i was 20-40% of normal. Dopamine reduced TRH-stimulated PRL release by greater than 90% and abolished the plateau, yet the calcium responses to TRH were at least 50% of normal. Although dopamine prevented the plateau component of peptide-stimulated [Ca]i, the plateau phase of efflux persisted. Thus TRH and ANG II may control at least two cell-associated calcium pools, one readily depleted and the other highly resistant to depletion, without evidence for stimulation of calcium uptake. Dopamine inhibits PRL release stimulated by these peptides, with a relatively greater influence on the plateau component, through mechanisms only minimally related to calcium flux. Dopamine may slightly increase the extrusion of calcium mobilized by these peptides and thus may limit the anticipated increase in [Ca]i. PMID- 1902062 TI - Vasopressin uptake by hypothalamopituitary axis and pineal gland in guinea pigs. AB - The uptake of circulating arginine vasopressin (AVP) by the pituitary gland (anterior lobe), pineal gland, and hypothalamus (ventromedial part) was investigated in an isolated in situ perused brain of anesthetized guinea pig. Kinetic experiments revealed saturable AVP uptake in all studied regions with Km values of 0.79, 0.19, and 0.76 microM and maximum velocity values of 22, 2.1, and 1.6 pmol.min-1.g-1 for the pituitary gland, pineal gland, and hypothalamus, respectively. The nonsaturable components (diffusion constants) were not significantly different from zero. Peptide fragments, L-phenylalanine, and Bestatin (an aminopeptidase inhibitor) did not interfere with AVP uptake. However, uptake of AVP was strongly inhibited in the presence of the V1 antagonist [1-(beta-mercapto-beta-beta-cyclopentamethylenepropionic acid), 2-(O methyl)tyrosine]AVP at 2.7 microM, and regional Ki values, assuming that the observed inhibitions were purely competitive, ranged between 0.32 and 2.23 microM. The V2 agonist 1-desamino-8-D-AVP at 2.7 microM produced only a weak inhibition of AVP uptake, and regional Ki values ranged between 9.56 and 21.3 microM. It is concluded that specific uptake mechanisms in the hypothalamopituitary axis and pineal gland are sensitive enough to detect blood borne AVP under the physiological hormonal state. It is suggested that AVP binding in situ is primarily related to V1 receptors, which may be involved in mediating the central effects of this circulating peptide. PMID- 1902063 TI - Characterization of L-glutamine transport by pulmonary artery endothelial cells. AB - This study characterized the transport of L-glutamine by porcine pulmonary artery endothelial cells (PAECs). Uptake of 50 microM glutamine was determined and found to be linear for at least 45 min. The sodium-dependent velocity represented greater than 95% of the total uptake at all time points. Kinetic studies of glutamine uptake at concentrations between 0.005 and 10 mM showed a single saturable high-affinity carrier with a Michaelis constant of 100 +/- 6 microM and a maximal transport velocity of 1.0 +/- 0.08 nmol.mg protein-1.30s-1. Glutamine uptake by PAECs was markedly inhibited in the presence of L-cysteine, L threonine, or L-alanine; lesser degrees of inhibition occurred when histidine and arginine were added. 2-Methylaminoisobutyric acid and 2-aminobicyclo [2,2,1]heptanedicarboxylic acid had little effect on glutamine uptake. Lithium did not substitute for sodium, strongly suggesting that L-glutamine was not transported by system N. Furthermore, transport of glutamine was not affected by hormones or by changes in external pH. Based on the intolerance of this high affinity carrier to N-methylated substrate, its insensitivity to pH and hormonal regulation, and the failure of lithium to substitute for sodium, as well as its inhibition by alanine and cysteine, we conclude that in porcine pulmonary artery endothelial cells L-glutamine is predominantly taken up through system ASC. PMID- 1902064 TI - Complement activation by cigarette smoke. AB - Lung disease secondary to cigarette smoking is associated with an influx of neutrophils and monocytes into the lower respiratory tract. To determine whether cigarette smoke can generate chemotactic activity, human serum was exposed to cigarette smoke and evaluated for neutrophil and monocyte chemotactic activity. Serum exposed to cigarette smoke attracted significantly greater numbers of neutrophils and monocytes compared with normal human serum exposed to air (P less than 0.01, both comparisons). The increase in chemotactic activity was partially attenuated by EDTA but not by ethylene glycol-bis(beta-aminoethyl ether) N,N,N',N'-tetraacetic acid (EGTA) and MgCl2 (P greater than 0.05, both comparisons), suggesting activation of the alternate complement pathway. To evaluate the capacity of cigarette smoke to activate the complement system, smoke exposed serum was evaluated for cleavage of properdin factor B and C3 using immunoelectrophoresis and for C5a using a radioimmunoassay. Cleavage of properdin factor B and C3 was observed in the smoke-exposed serum and C5a was detected in the smoke-exposed serum (112 +/- 31 ng/ml). These data suggest that complement activation may play a role in directing the influx of neutrophils and monocytes into the lungs of cigarette smokers. PMID- 1902065 TI - Rat alveolar epithelial cells concomitantly express plasminogen activator inhibitor-1 and urokinase. AB - There is considerable evidence to suggest that intra-alveolar plasminogen activation is instrumental in many aspects of inflammatory lung injury and subsequent tissue repair. Rat alveolar epithelial cells produce large quantities of urokinase-type plasminogen activator (uPA) in vitro, and uPA expression is modulated in association with cellular differentiation and exposure to inflammatory mediators. We now report that these cells also secrete heat-stable PA inhibitory activity having the characteristics of PA inhibitor type 1 (PAI-1). In particular, immunoreactive PAI-1 was demonstrable in conditioned media, cell lysates, and extracellular matrix from epithelial cell cultures. As alveolar epithelial cells differentiated in vitro, secreted PA inhibitor activity increased significantly from 104 +/- PAI U/ml (n = 5, mean +/- SE) on day 2 to 442 +/- 150 on day 7 in parallel with increases in secreted and matrix-associated immunoreactive PAI-1. PAI-1 mRNA expression decreased over this same period suggesting posttranscriptional regulation. The levels of both newly synthesized antigen and PAI-1 mRNA were increased by exposure to lipopolysaccharide and tumor necrosis factor-alpha. Thus, by the coexpression of uPA and PAI-1, the alveolar epithelium may actively regulate the generation of plasmin in both the normal and injured alveolus. PMID- 1902066 TI - Synthesis of eicosanoids by isolated guinea pig tracheocytes. AB - Epithelial cells from the guinea pig trachea (tracheocytes) have been separated from the lamina propria by incubation with EDTA. Contaminating eosinophils were removed by plating on guinea pig immunoglobulin G (IgG)-coated plates. Purity of the cell suspension was assessed by electron microscopy. Enzyme immunoassay analyses of supernatants of guinea pig tracheocytes incubated with 10 microns arachidonic acid (AA) in the presence or absence of 2 microns ionophore A23187 showed that the cells released up to eight times more thromboxane, prostaglandin E2, and 6-ketoprostaglandin F1 alpha than control cells. Ionophore A23187 by itself stimulated to a smaller extent the release of these eicosanoids and did not potentiate the effect of AA. The release of cyclooxygenase products by these cells was highly modified by cell densities in the incubation media. The release of leukotrienes (LT) by stimulated epithelial cells was also investigated using reverse-phase high-performance liquid chromatography. Our results showed that the cells could not release LT on incubation with ionophore A23187 and/or AA. However, the cells released LTB4 in the medium on incubation with 2 microns LTA4. Peptido-leukotrienes were not detected. These results indicated that guinea pig tracheocytes have the cyclooxygenase and the LTA4 hydrolase but not the 5 lipoxygenase. It is postulated that tracheocytes may participate in transcellular metabolism of LTA4 generated by other cell types. PMID- 1902067 TI - Is empathy cost efficient? AB - In an attempt to constrain rising health-care costs, third-party payers are currently encouraging psychiatrists and other physicians to focus on the financial aspects of their treatment approaches. This paper has attempted to address the impact of this cost-efficient attitude on our empathy and by tracking the evolution of our health-care-delivery system since the turn of the century. I have described three overlapping phases: the humanist, the scientific, and the current corporate phase, and emphasized the importance or trivialization of an empathic practice-style associated with each stage. I have warned how the corporate delivery system, with its focus on cost constraints, may inhibit our capacity to be empathic by stimulating self-serving concerns about the corporation's monetary welfare and our own financial well-being. This unempathic stance may result in treatment being driven by financial factors that override clinically driven needs of the patient. At its extreme, this approach may render psychiatrists vulnerable for viewing patients as bad objects that deprive financially, and for countertransferentially retaliating against them through "warehousing" and abandonment. PMID- 1902068 TI - t-PA, PAI, and protein C before and after vascular occlusion of the upper limb in patients with Raynaud's phenomenon. AB - Tissue plasminogen activator (t-PA) and its inhibitor (PAI) were assessed in venous blood drawn before and after venous occlusion (bvo, avo) for 33 patients with Raynaud's phenomenon (RP), 14 with primary RP (PRP), 9 with suspected secondary RP (SSRP), and 10 with definite collagen disease and secondary RP (SRP). There were significant differences in PAI values avo between PRP (and controls), SSRP, and SRP. PAI activity decreased significantly avo only in controls and in PRP, and there was significant t-PA antigen elevation avo in the same groups. In addition, since PAI is neutralized by activated protein C (PC), both PC antigen and PC activity were assessed avo and bvo. PC Ag remained unchanged in all groups, with PC activity significantly lower than controls in SRP and SSRP. Finally the authors looked for interference of anticardiolipin antibodies (ACA) and lupus-like anticoagulant (LAC) with the PC system in collagen disease-associated RP. Specific IgG ACA were found in only 1 patient with SRP. In conclusion, there is an endothelial derangement, involving t-PA release and PAI, in SSRP and SRP patients. The reduced PC activity in these latter groups appears to be due to increased PAI influence rather than to ACA/LAC. PMID- 1902070 TI - [Primary meningococcal conjunctivitis: report of a case]. PMID- 1902071 TI - Immunohistochemical characterization of a new anti-carcinoembryonic antigen monoclonal antibody. AB - A novel anti-CEA monoclonal antibody C234 with no cross-reactivity to other members of CEA gene family was produced by immunization with heat-treated CEA. The immunoreactivity of C234 was tested on formalin fixed normal and neoplastic tissues by peroxidase/anti-peroxidase technique. None of normal tissues from healthy or diseased individuals, except for normal colonic mucosa were stained. On the other hand, all 26 colorectal adenocarcinomas, 8 gastric adenocarcinomas, 3 of 7 pancreatic adenocarcinomas, and one small bowel duodenum carcinoma were immunoreactive. None of primary hepatocellular carcinomas expressed CEA. However, only 40 of 87 neoplasms of non-gastrointestinal origin were stained. Thus, the antibody can recognize gastrointestinal tumors and differentiate them from neoplasms of other histological origin. PMID- 1902069 TI - Eicosanoids and platelet-activating factor in allergic respiratory diseases. AB - The nature of the lipid mediators released at an inflammatory site in the airways is dependent not only on the individual cells and inflammatory stimuli present but also on a complex interaction between neighboring cells and their lipid products. These lipid mediators share overlapping activities, and current research is directed toward determining the critical molecules involved in the pathogenesis of particular inflammatory states. How may the release of these lipid mediators play a role in the pathogenesis of asthma? Allergic persons after inhalation of specific allergen have a dual bronchospastic response. The early asthmatic response occurring shortly after allergen challenge is most likely secondary to the action of bronchoconstrictor molecules (e.g., LTC4, PGD2, PAF) released by human lung mast cells as a consequence of IgE-mediated degranulation. An inflammatory process than occurs in the airways that is characterized by an influx of eosinophils and neutrophils into the airway epithelium and bronchial fluids. This inflammatory response corresponds to the late asthmatic phase occurring several hours after allergen challenge. Release of sulfidopeptide leukotrienes, PAF, and cyclooxygenase products by cells infiltrating the airways may be involved in the bronchial smooth muscle constriction, mucosal edema, and mucus hypersecretion observed during these late asthmatic responses. In the future, the therapeutic use of specific antagonists of the biosynthetic enzymes of the 5-lipoxygenase pathway and receptor antagonists of the eicosanoids and PAF holds great promise for the modulation of airway inflammation. PMID- 1902072 TI - DMBA-induced uterine vascular tumors in BALB/c mice: ovary-dependent carcinogenic response. AB - Female BALB/c mice treated with a single intraperitoneal injection of 1 mg of 7, 12-dimethylbenz(a)anthracene (DMBA) at 4, 8 and 20 weeks of age showed a high incidence of uterine vascular tumors. Bilateral ovariectomy preceding DMBA treatment almost completely inhibited the induction of vascular tumors, while ovariectomy following DMBA treatment resulted in endometrial gland atrophy and a high incidence of vascular tumors. Vascular tumors were also induced when DMBA was given to neonatal androgenized mice, whereas among neonatal androgenized and normal female mice not treated with DMBA the incidence was 0%. Histological examinations revealed benign hemangiomas or angiosarcomas. In contrast, DMBA treated male BALB/c mice and orchiectomized mice, and DMBA-untreated males showed no vascular tumors. A striking ovarian dependence of induction of uterine vascular tumors was observed. PMID- 1902073 TI - Modulation of cell growth and differentiation induced by prostaglandin D2 in the glioma cell line C6. AB - Prostaglandins are produced mainly from arachidonic in various normal and neoplastic tissues and are well-known to be involved in the regulation of tumor cell proliferation, differentiation and metastasis. Prostaglandin D2 is cytotoxic to several human tumor cell lines, has antitumoral activity in vitro and is reported to be antimetastatic. However, the effects of prostaglandin D2 on tumoral cell differentiation have not been clarified. This paper studies the effects of prostaglandin D2 on C6 rat glioma cell differentiation and proliferation. Prostaglandin D2 administration in the culture medium is observed to alter cell morphology and cytoskeleton filament patterns. These alterations suggest a cell maturation, and correlate with a drop in proliferating capacity. The antitumoral activity of prostaglandin D2 involves a biomodulation of cell parameters which would affect neoplastic processes. PMID- 1902074 TI - Modulation of epidermal growth factor receptors by gamma interferon in a breast cancer cell line. AB - Interferons (IFNs) may inhibit cell growth via their interaction with growth factors and their receptors. We examined the ability of IFN to modulate Epidermal Growth Factor (EGF) receptor binding in a human breast carcinoma cell line, MDA 468. Gamma interferon and alpha interferon inhibited growth of MDA 468 cells in a dose and time-dependent manner. IFN-gamma and Epidermal Growth Factor (EGF), a known inhibitor of MDA 468 growth, inhibited growth in an additive fashion. Growth inhibition by gamma but not alpha interferon was associated with a decrease in the number of EGF receptors (EGFRs) after 5 days. Scatchard analysis of receptor binding data revealed that gamma but not alpha interferon reduced the number of available EGF receptor binding sites without any change in the affinity of the receptor. IFN significantly affected EGF receptor expression, and the decrease in receptor expression was associated with growth inhibition. PMID- 1902076 TI - Hematological toxicity of adjuvant portal liver infusion with fluorouracil, mitomycin and heparin. AB - Adjuvant perioperative liver infusion chemotherapy with fluorouracil, mitomycin and heparin caused mild but significant myelosuppression in the first two postoperative weeks. This was associated with a slightly increased bleeding tendency. Mortality was not increased. Future trials might combine chemotherapy with hematopoietic growth factors in order to minimize myelosuppression. PMID- 1902075 TI - Antitumor activity of oxysterols. Effect of two water-soluble monophosphoric acid diesters of 7 beta-hydroxycholesterol on mastocytoma P815 in vivo. AB - Oxysterols, a family of naturally occurring products, have been shown to possess several biological activities. In particular, they are more toxic towards tumor cells than towards normal cells. In addition, they markedly modify immune cell responses. To carry out in vivo studies, we have synthesized phosphodiesters of 7 beta-hydroxycholesterol (JB69 and XA29). These water-soluble prodrugs have a similar toxicity to their parent compound under in vitro conditions. When administered intraperitoneally to mice bearing the P815 mastocytoma, they induced significant increases in life span. The results depend on the administration protocol. Under appropriate conditions, 20 to 40% of treated mice recover completely. This, together with their immunological effect, suggests that these oxysterols should be considered to be agents for immunochemotherapeutic investigations. By their ability to inhibit HMG CoA reductase, they may prevent the biosynthesis of prenyl groups whose coupling to oncogenes is responsible for the biological activity expression of the latter. Several indications are compatible with an effect on the cell membrane. Our recent studies have shown Protein Kinase C to be a target of oxysterols. On the basis of results obtained by our group and by others, we believe that oxysterols may form a new class of antitumor agents. PMID- 1902077 TI - Heterogeneous effects of interferon on antitumor agents' cytotoxicities to human colon carcinoma cell lines. AB - Six established human colon carcinoma cell lines that segregated into three groups with different degrees of differentiation were treated using three subclasses of interferons as single agents and in combination with either 5 fluorouracil, cis-platinum, or adriamycin. The cytotoxicities of the combination treatments were heterogeneous and did not relate to the cell's levels of differentiation. Our data suggest that the optimal combinations of interferons and chemotherapeutic agents are independent of the differentiation state of the colon cancer cells. PMID- 1902078 TI - Cytokine release from mononuclear cells in patients irradiated for breast cancer. AB - Mononuclear cells from blood of 19 breast cancer patients were cultured in vitro before and following postoperative radiation treatment. Interferon-gamma (IFN gamma), tumour necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1) were determined in supernatants from stimulated and unstimulated cultures with or without addition of indomethacin. The release of all three cytokines was uninhibited in tumour patients. Spontaneous IL-1 secretion was increased in patients compared to controls. Indomethacin enhanced IFN-gamma release and spontaneous and induced TNF-alpha secretion in all groups but stimulated IL-1 only in irradiated patients. In patients with a low tumour burden, ability to produce cytokines seems to be unchanged although increased spontaneous IL-1 secretion indicates macrophage activation. Cyclooxygenase inhibition in conjunction with irradiation might be tried as a therapeutic modality in patients with cancer. PMID- 1902079 TI - Direct action of gonadotropin-releasing hormone (LH-RH) analogue on ovary: an alternative acting mechanism of buserelin. AB - The mechanisms by which gonadotropin-releasing hormone (LH-RH) analogue buserelin exerts direct action on the ovary was investigated. The analogue inhibited the luteinizing hormone (LH)-induced increase of steroidogenesis by rat ovarian granulosa cells in a dose-dependent manner. The LH-RH analogue did not alter binding capacity and affinity of 125I-LH to granulosa cells, suggesting the involvement of post-receptor mechanism. Likewise, the analogue caused inositol trisphosphate (IP3) formation as a result of stimulated inositol-phospholipid turnover. Half maximal effects of both steroidogenesis suppression and IP3 production occurred at 10 nM buserelin. These findings indicate that the inhibitory action of buserelin on granulosa cell function is mediated by IP3 (or calcium)-dependent mechanisms. Buserelin, in addition to its well-known action at pituitary level, exerts a direct inhibition of ovarian steroidogenesis at gonadal level without changes in gonadotropin receptors. PMID- 1902080 TI - Some observations on the binding properties of alfalfa mosaic virus to polystyrene and its significance to indirect ELISA. AB - The adsorption and retention properties of native (unfixed) and glutaraldehyde fixed alfalfa mosaic virus (AMV) antigens to the polystyrene of ELISA plates were studied using [35S]-labelled virus preparations. It was shown that adsorption was a temperature-dependent, relatively slow process which varied between different AMV isolates. The amount of virus antigen adsorbed was dependent on the type and pH of the suspending buffer. Although native virus antigen adsorbed very efficiently at high pH when the particles had dissociated, significant amounts also adsorbed at pH 7.0, or lower. However, glutaraldehyde-fixed virus particles which retained their integrity even at pH as high as 9.6, adsorbed much more efficiently than native virus antigen above pH 9.0, but hardly at all around pH 7.0. The wide variation in adsorption of AMV antigen to microtitre plates under even slightly different conditions had significant influence on ELISA readings, which calls for extreme caution in interpreting serological results from indirect ELISA when antigen is used to coat the microtitre plates. PMID- 1902081 TI - Dermal and serological response against Pseudomonas aeruginosa in sheep bred for resistance and susceptibility to fleece-rot. AB - Genetically select lines of Merino sheep have been bred at Trangie (NSW Agriculture and Fisheries) for resistance (R) or susceptibility (S) to fleece-rot and flystrike. It is believed that fleece characters are primarily responsible for the R or S phenotype. When transferred to the wetter coastal environment of Sydney, R and S sheep with no more than 6 weeks wool cover, continued to show significant differences in the incidence and severity of fleece-rot dermatitis. To test the hypothesis that these sheep might also exhibit differences in their local skin reactions and immune responsiveness, 3 intradermal injections of killed Pseudomonas aeruginosa were administered at monthly intervals. After primary intradermal challenge, R sheep had a higher incidence of skin induration and a stronger inflammatory response (increased induration diameter) than S sheep. Compared to S sheep, R sheep also developed higher levels of circulating antibodies against whole cell antigen and both inner and outer membrane proteins of P. aeruginosa. These responses were maintained in R sheep with each consecutive challenge while S sheep showed a decline in their immune responsiveness. Differences in antibody response against outer membrane proteins were also detected when antigenically naive sheep from each genetic line were sensitised by epicutaneous challenge with P. aeruginosa under experimental wetting conditions. Intradermal challenge of these animals 6 months later with outer membrane proteins, revealed a late maximum (72 h) in the development of induration diameters for R sheep while S animals showed maximal induration diameters by 24 h. However, there was no significant difference in induration response between 24 h and 72 h within each group of sheep.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1902082 TI - Relationship between arachidonate release and exocytosis in permeabilized human neutrophils stimulated with formylmethionyl-leucyl-phenylalanine (fMetLeuPhe), guanosine 5'-[gamma-thio]triphosphate (GTP[S]) and Ca2+. AB - The role of two G-proteins, Gp and Ge, in the stimulus-secretion pathway has been proposed on the basis of studies where GTP analogues have been introduced into permeabilized cell preparations. In this study, evidence is provided that two G proteins are also involved when a receptor-directed agonist is used. Intact human neutrophils were made refractory to formylmethionyl-leucyl-phenylalanine (fMetLeuPhe) stimulation by metabolic inhibition and then permeabilized with streptolysin O to compare the intracellular requirements for exocytosis from specific and azurophilic granules and arachidonate release. In the presence of 1 microM-Ca2+ and 1 mM-MgATP, fMetLeuPhe or guanosine 5'-[gamma-thio]triphosphate (GTP[S]) induce secretion from both granule types as well as arachidonate release. Secretion and arachidonate release owing to fMetLeuPhe can occur in the absence of ATP, conditions under which G-protein-mediated activation of phospholipase C is suppressed. GTP[S]-induced secretion can also occur in the absence of MgATP, but GTP[S]-induced arachidonate release cannot. It is concluded that fMetLeuPhe, like GTP[S], stimulates secretion by interacting with another G protein-mediated reaction apart from Gp. Evidence is provided that a possible target for the second G-protein-mediated reaction involved in fMetLeuPhe-induced secretion (but not GTP[S]-induced secretion) is phospholipase A2. PMID- 1902083 TI - Biosynthesis of heparin. Use of Escherichia coli K5 capsular polysaccharide as a model substrate in enzymic polymer-modification reactions. AB - A capsular polysaccharide from Escherichia coli K5 was previously found to have the same structure, [-(4)beta GlcA(1)----(4)alpha GlcNAc(1)-]n, as that of the non-sulphated precursor polysaccharide in heparin biosynthesis [Vann, Schmidt, Jann & Jann (1981) Eur. J. Biochem. 116, 359-364]. The K5 polysaccharide was N deacetylated (by hydrazinolysis) and N-sulphated, and was then incubated with detergent-solubilized enzymes from a heparin-producing mouse mastocytoma, in the presence of adenosine 3'-phosphate 5'-phospho[35S] sulphate ([35S]PAPS). Structural analysis of the resulting 35S-labelled polysaccharide revealed the formation of all the major disaccharide units found in heparin. The identification of 2-O-[35S]sulphated IdoA (L-iduronic acid) as well as 6-O [35S]sulphated GlcNSO3 units demonstrated that the modified K5 polysaccharide served as a substrate in the hexuronosyl C-5-epimerase and the major O sulphotransferase reactions involved in the biosynthesis of heparin. The GlcA units of the native (N-acetylated) E. coli polysaccharide were attacked by the epimerase only when PAPS was present in the incubations, whereas those of the chemically N-sulphated polysaccharide were epimerized also in the absence of PAPS, in accord with the notion that N-sulphate groups are required for epimerization. With increasing concentrations of PAPS, the mono-O-sulphated disaccharide unit-IdoA(2-OSO3)-GlcNSO3- was progressively converted into the di-O sulphated species -IdoA(2-OSO3)-GlcNSO3(6-OSO3)-. A small proportion of the 35S labelled polysaccharide was found to bind with high affinity to the proteinase inhibitor antithrombin. This proportion increased with increasing concentration of PAPS up to a level corresponding to approximately 1-2% of the total incorporated 35S. The solubilized enzymes thus catalysed all the reactions required for the generation of functional antithrombin-binding sites. PMID- 1902085 TI - Models of human platelet thrombospondin in solution. A dynamic light-scattering study. AB - The translational diffusion coefficient (D20,w) of human platelet thrombospondin was measured by dynamic light-scattering. D20,w, measured in 20 mM-Hepes buffer, pH 7.4, containing 350 mM-NaCl and 2 mM-CaCl2, was 1.73(+/- 0.02) x 10(-7) cm2.s 1. After removal of bound Ca2+ by addition of EDTA, D20,w decreased to 1.56(+/- 0.04) x 10(-7) cm2.s-1; this was not a consequence of aggregation. D20,w showed little sensitivity to NaCl concentration between 130 and 550 mM. Through hydrodynamic analysis combining D20,w and other parameters taken from the literature, two major types of models for thrombospondin can be proposed: either classic compact models (i.e. low degree of hydration) such as prolate or oblate ellipsoids with a high axial ratio (greater than 20) or models of low axial ratio made of multiple subunits with significant cavities (i.e. high degree of hydration). PMID- 1902084 TI - Abundance of the alpha-subunits of Gi1, Gi2 and Go in synaptosomal membranes from several regions of the rat brain is increased in hypothyroidism. AB - 1. Rats (4 weeks old) were made hypothyroid by treatment with propylthiouracil together with a low-iodine diet for a further period of 4 weeks. Synaptosomal membranes were obtained from six anatomical regions of the brain. 2. The abundances in these membranes of the G-protein alpha-subunits Gi1 alpha, Gi2 alpha and Go alpha were measured by quantitative immunoblotting. 3. Hypothyroidism significantly increased the abundances of all three G-protein subunits in membranes from the cerebral cortex and the striatum. In the medulla oblongata and the hippocampus the abundances of Gi2 alpha and Go alpha were increased significantly. By contrast, in the cerebellum only Go alpha was increased, and in the hypothalamus only Gi2 alpha was increased. 4. It is suggested that this up-regulation of G-protein abundances may modify signalling pathways and may contribute to the functional changes that are observed in the central nervous system in hypothyroidism. PMID- 1902086 TI - Chondroitin sulphate and keratan sulphate are almost isosteric. AB - Keratan sulphate and chondroitin sulphate (KS and CS) in the 2-fold helical configurations that are prevalent in solution are of very similar tacticity. The chiral centres, anionic sites and hydrophobic patches are in identical conformations. Only the position of the acetamido group varies from CS to KS, but part of its intramolecular H-bonding potential in CS is retained in KS. The formation of tertiary aggregates, observed in vitro and in tissues, is explicable on these bases. The proposal that KS may be a functional substitute for CS [Scott & Haigh (1988) J. Anat. 158, 95-108] under low-O2 conditions is relevant. PMID- 1902087 TI - Isolation and characterization of the integral glycosaminoglycan constituents of human amyloid A and monoclonal light-chain amyloid fibrils. AB - Amyloid fibrils were isolated by extraction in water from the livers and spleens of four patients who had died of monoclonal, light-chain (AL)-type, systemic amyloidosis and one with reactive systemic, amyloid A protein (AA)-type amyloidosis. Each fibril preparation contained 1-2% by weight of glycosaminoglycan (GAG) which was tightly associated with the fibrils and not just co-isolated from the tissues with them. After exhaustive digestion of the fibrils with papain and Pronase, the GAGs were specifically precipitated with cetylpyridinium chloride and were identified by cellulose acetate electrophoresis and selective susceptibility to specific glycosidases. All the preparations contained approximately equal amounts of heparan sulphate and dermatan sulphate. There was no evidence for the presence of chondroitin sulphate or other GAGs. Fine structural analysis by oligosaccharide mapping in gradient polyacrylamide gels, following partial digestion with specific glycosidases, showed very similar structures among the heparan sulphates and the dermatan sulphates, respectively. GAGs were also extracted by solubilizing amyloid fibrils in 4 M-guanidinium chloride followed by CsCl density-gradient ultracentrifugation. Although a minor proportion of the GAG material obtained in this way was apparently in the form of proteoglycan molecules, most of it was free GAG chains. The presence in amyloid fibrils of different types, in different organs and from different patients of particular GAG classes with similar structures supports the view that these molecules may be of pathogenic significance. PMID- 1902089 TI - Abnormal and deficient processing of beta-amyloid precursor protein in familial Alzheimer's disease lymphoblastoid cells. AB - Western blot analysis showed abnormal processing of beta-amyloid precursor protein (APP) in lymphoblastoid cell lines (LCLs) of familial Alzheimer's disease (FAD). Antibody raised against central APP751 revealed that media of early and late-onset FAD LCLs had highly increased amounts of a 120 kD long-lived. SDS stable, heat-labile complex of the Kunitz protease inhibitor domain of secreted APP and a approximately 70 kD FAD-specific, yet unidentified serine protease. Antibody against the beta A4-cytoplasmic domain showed a slower APP processing and increased amounts of 16 kD C-terminal preamyloid in lysates of early and late onset FAD LCLs, first indicating a deficient intra-beta A4 proteolysis in FAD as a possible cause of abundant amyloid deposits in AD brain. PMID- 1902088 TI - Selective Ca2(+)-dependent interaction of calmodulin with the head domain of synapsin 1. AB - The calcium-dependent regulatory protein calmodulin is a critical element in the machinery regulating exocytosis at nerve terminals. Okabe & Sobue [(1987) FEBS Lett. 213, 184-188] showed that calmodulin interacts with one of the proteins intimately connected with the neuronal exocytotic process, i.e. synapsin 1. We have investigated the site at which calmodulin interacts with synapsin 1. We find that it is possible to generate chemically cross-linked Ca2(+)-dependent complexes between synapsin 1 and calmodulin in vitro, and have used covalent cross-linking in conjunction with calmodulin affinity chromatography to identify fragments of synapsin 1 that interact with calmodulin. Ca2(+)-dependent calmodulin binding is restricted to the 'head' domain (residues 1-453 in bovine synapsin 1). Within this domain the binding site is located in a unique 11 kDa Staphylococcus aureus V8 proteinase generated fragment. This fragment does not contain the site for cyclic-AMP-dependent phosphorylation and therefore does not represent the N-terminus of the protein. PMID- 1902090 TI - Receptors for insulin interact with Gi-proteins and for epidermal growth factor with Gi- and Gs-proteins in rat pancreatic acinar cells. AB - In rat pancreatic acinar cells epidermal growth factor (EGF) and insulin increase both basal and cholecystokinin (CCK-OP) stimulated amylase release in vitro (1) as a long term function of this tissue. Here we show that preincubation of isolated plasma membranes with EGF or with insulin leads to increased incorporation of the GTP-photoaffinity analogue [alpha-32P]GTP-gamma-azidoanilide into 40/41 kDa proteins and to reduction of pertussis toxin- (PT) catalyzed [alpha-32P]ADP-ribosylation of three 40/41 kDa proteins which had been previously identified as Gi1, Gi2 and Gi3 (2). In the presence of GTP gamma S, EGF- and insulin-induced inhibition of PT-mediated [alpha-32P]ADP-ribosylation of 40/41 kDa proteins is eliminated. EGF enhances cholera toxin- (CT) mediated ADP ribosylation of all three 40/41 kDa Gi-proteins as well as of five 45 and four 48/50 kDa proteins, which had been previously identified as Gs-proteins (2), whereas insulin has no effect. We conclude from our data that both EGF and insulin interact with the same Gi-proteins as CCK-OP does, whereas EGF additionally interacts with nine Gs-proteins. It is likely that one, two or all three 40/41 kDa Gi-proteins are involved in insulin- and EGF-induced potentiation of CCK-OP-stimulated enzyme secretion. In addition interaction of EGF with Gs protein could play a role in the potentiation of CCK-OP-induced enzyme secretion from pancreatic acinar cells. PMID- 1902091 TI - The cAMP-dependent protein kinase phosphorylates the rap1 protein in vitro as well as in intact fibroblasts, but not the closely related rap2 protein. AB - The products of rap genes (rap1A, rap1B and rap2) are small molecular weight GTP binding proteins that share approximately 50% homology with ras-p21s. It had previously been shown that a rap1 protein (also named Krev-1 or smg p21) could be phosphorylated on serine residues by the cAMP-dependent protein kinase (PKA) in vitro as well as in intact platelets stimulated by prostaglandin E1. We show here that the rap1A protein purified from recombinant bacteria is phosphorylated in vitro by the catalytic subunit of PKA and that the deletion of the 17 C-terminal amino acids leads to the loss of this phosphorylation. This suggests that the serine residue at position 180 constitutes the site of phosphorylation of the rap1A protein by PKA. The rap1 protein can also be phosphorylated by PKA in intact fibroblasts; this phenomenon is independent of their proliferative state. In contrast, protein kinase C (PKC) does not phosphorylate the rap1 proteins, neither in vitro nor in vivo. Finally, the 60% homologous rap2 protein is neither phosphorylated in vitro nor in vivo by PKA or PKC. PMID- 1902092 TI - A hemopoietic specific gene encoding a small GTP binding protein is overexpressed during T cell activation. AB - We have isolated, from a human B cell line cDNA library, a cDNA (Gx) encoding a small G protein identical to rac 2, a member of the ras superfamily. Gx/rac 2 gene is expressed as a unique mRNA of 1,7 Kb in peripheral blood lymphocytes, in purified B and T cells, in thymus as well as in several B and T cell lines. It is not expressed in many other tissues analysed including liver, brain, lung, heart and kidney. Upon in vitro stimulation with phytohemagglutinin A, peripheral blood lymphocytes show a clear increase of the Gx/rac 2 mRNA after 6 hours; a 30-50 fold accumulation is reached at 24 hours and persists thereafter. Purified T lymphocytes exhibit a similar increase in Gx/rac 2 mRNA expression upon mitogenic stimulation. Therefore, the expression of the Gx/rac 2 gene appears to be restricted to cells of the hemopoietic lineage and to be strongly stimulated during T cell activation. Gx/rac 2 protein must fulfill a specific role in activated T cells that could provide a new model for studying the function of small G proteins. PMID- 1902093 TI - Identification of the G-protein alpha-subunit encoded by alpha o2 cDNA as a 39 kDa pertussis toxin substrate. AB - A novel form of the Go alpha-subunit (alpha o2) has been identified by molecular cloning (Hsu et al., J. Biol. Chem. 265, 11220-11226, 1990). An antibody was generated against a synthetic peptide corresponding to a region of the protein encoded by alpha o2 cDNA. The antibody reacted with an apparently single 39 kDa protein in membrane preparations of rodent brain and with a 39 kDa pertussis toxin substrate in membranes of rodent neuroendocrine and pituitary cells. A previously produced antibody raised against a region common to proteins encoded by alpha o2 cDNA and the previous cloned alpha o1 cDNA (Itoh et al., Proc. Natl. Acad. Sci. USA 83, 3776-3780, 1986) recognized proteins of 39 and 40 kDa in preparations of bovine, porcine and rodent brain and pertussis toxin substrates of 39 and 40 kDa in membranes of rodent neuroendocrine and pituitary cells. We conclude that the 39 kDa Go alpha subunit is encoded by alpha o2 cDNA. PMID- 1902094 TI - Estrogen induces c-fos expression specifically in the luminal and glandular epithelia of adult rat uterus. AB - It was previously shown that injection of 17 beta-estradiol into adult ovariectomized rats induces a rapid and transient increase of c-fos gene transcription in the uterus. Immunohistochemical analysis now shows that estrogen activates c-fos specifically in the luminal and glandular epithelial cells of the endometrium, which are the only uterine cells responding to the hormone with DNA synthesis and cell proliferation, and not in estrogen receptor positive stromal and myometrial cells. This finding suggests that c-fos is involved in the mechanism of estrogen regulation of uterine epithelial cell proliferation and, furthermore, that the c-fos activation by estrogen is cell type dependent. PMID- 1902095 TI - The primary structure of Tetrahymena profilin. AB - The cDNA of Tetrahymena profilin was cloned and sequenced. The deduced product has a molecular mass of 16,785 Da which is the largest among profilins known so far. Tetrahymena profilin shows higher homologies with lower eukaryotic profilins than with mammalian profilins. Although the homologies with mammalian and lower eukaryotic profilins are only 20-29% which is the lowest one among lower eukaryotic profilins, the N- and C-terminal regions of Tetrahymena profilin are considerably conserved as those in other profilins, suggesting that these regions are responsible for the essential properties common to profilins. PMID- 1902096 TI - Murine recombinant leukemia inhibitory factor modulates inhibitory effect of 1,25 dihydroxyvitamin D3 on alkaline phosphatase activity in MC3T3-E1 cells. AB - We demonstrated murine leukemia inhibitory factor (mLIF) mRNA in osteoblastic MC3T3-E1 cells, but not mLIF in their conditioned medium. Recombinant mLIF had an inhibitory effect on alkaline phosphatase (ALP) activity, but not on DNA synthesis, in these mLIF-free cells. This inhibitory effect was not prostaglandin E2 dependent. mLIF also modulated the inhibitory effect of 1,25 dihydroxyvitamin D3 [1,25(OH)2D3] on ALP activity, partly via down regulation of 1,25(OH)2D3 binding sites. These results suggest that LIF may play a role in regulating osteoblast differentiation. PMID- 1902097 TI - Synthesis of a new inhibitor of the UDP-GalNAc:polypeptide galactosaminyl transferase. AB - Reaction of UDP-glucose with 1-hexadecanesulfonyl chloride (C16H33SO2Cl) in pyridine gave a new inhibitor of O-glycosylation. This reaction product was purified by TLC and shown by 1H-NMR and by chemical analysis of phosphorus to be uridine 5'-phosphoric (1-hexadecanesulfonic) anhydride. This compound was tested against the GalNAc transferase. The UMP-hexadecanesulfonic-anhydride did inhibit this enzyme with 50% inhibition requiring 160 microM. The inhibition with respect to UDP-GalNAc concentration was of the competitive type. We also synthesized the UMP-1-octanesulfonic anhydride (C8) and the UMP-butanesulfonic anhydride (C4) to see way effect fatty acid had on activity. The inhibition was in the order C16:C8:C4. PMID- 1902098 TI - Inhibitory effect of interferon-gamma-dependent induction of major histocompatibility complex class II antigen by expressing exogenous poly(ADP ribose) synthetase gene. AB - Ia antigen, one of class II major histocompatibility complexes, was induced by treatment of mouse macrophage P388D1 cells with interferon-gamma. During the process, expression of poly(ADP-ribose) synthetase gene was depressed. We examined whether or not down-regulation of the synthetase was required for the interferon-gamma-dependent induction of Ia antigen. We constructed expression plasmid harboring metallothionein promoter-regulated synthetase gene. The enzyme activity and mRNA level of the synthetase were increased in exogenous synthetase gene-transfected clones. Induction of Ia antigen gene was strongly inhibited by expressing the exogenous synthetase gene upon treatment of the transfected clones with interferon-gamma. The result suggests that interferon-gamma-dependent down regulation of the synthetase may be involved in a step of the signal transduction to induce Ia antigen. PMID- 1902099 TI - A geranylgeranyltransferase for rhoA p21 distinct from the farnesyltransferase for ras p21S. AB - We have clarified that rhoA p21 purified from bovine aortic smooth muscle is geranylgeranylated at the cysteine residue in the C-terminal CAAX motif (A is an aliphatic amino acid and X is any amino acid). In this paper, a geranylgeranyltransferase for rhoA p21 (rhoA p21 GGT) was partially purified from bovine brain cytosol. This enzyme transferred a geranylgeranyl moiety from geranylgeranyl pyrophosphate to rhoA p21 having the CAAX motif (rhoA p21-CAAX) but not to rhoA p21 lacking the AAX portion. rhoA p21 GGT was separated from the previously reported farnesyltransferase for ras p21s (ras p21 FT) by column chromatographies and did not geranylgeranylate or farnesylate c-Ha-ras p21-CAAX. ras p21 FT did not geranylgeranylate or farnesylate rhoA p21-CAAX. These results indicate that rhoA p21 GGT distinct from ras p21 FT is present in bovine brain cytosol. PMID- 1902100 TI - Oxytocin contracts rat uterine smooth muscle in Ca2(+)-free medium without any phosphorylation of myosin light chain. AB - Contraction of rat uterine smooth muscle related to phosphorylation state of myosin light chain under various conditions was investigated. In the Ca2(+) containing medium, both high K+ and oxytocin induced marked contraction of the muscle accompanied by pronounced phosphorylation of myosin light chain. In the Ca2(+)-free medium, although both vanadate and oxytocin induced slight contraction, phosphorylation of myosin light chain was only evident for vanadate but not for oxytocin. It was suggested that another mechanism distinct from myosin light chain phosphorylation might be involved in Ca2(+)-independent contraction of uterine smooth muscle elicited by oxytocin. PMID- 1902101 TI - Selective modulation of the two antagonistic activities of protein kinase FA (the activator of ATP.Mg-dependent protein phosphatase). AB - The ATP.Mg-dependent protein phosphatase activating factor (FA) has been identified as a protein kinase. The results are unexpected since factor FA possesses two activities which are antagonistic. As a kinase, factor FA catalyzes protein phosphorylation, while as a phosphatase activator, it catalyzes protein dephosphorylation. In this report, we found that the two opposing activities of factor FA could be selectively modulated. For instance, heparin at concentrations of 0.1-0.3 mg/ml could stimulate FA to work preferentially as a kinase towards phosphorylation of proteins but simultaneously inhibit it to work as a phosphatase activator towards dephosphorylation of the same proteins. In a similar manner, alkaline pH could stimulate FA to work as a kinase but block it to work as a phosphatase activator. This is the first report providing initial evidence that the two opposing activities of factor FA can be selectively modulated in a reciprocal manner by various triggers, suggesting that a simultaneous coordinate control mechanism may well be involved in regulating the activities of factor FA in the cell. PMID- 1902102 TI - Spontaneous and mitomycin-C-induced micronuclei in human lymphocytes exposed to extremely low frequency pulsed magnetic fields. AB - The cytokinesis block micronucleus method, a very sensitive cytogenetic assay, was used to ascertain the possible genotoxic effects of extremely low frequency pulsed magnetic fields in phytohemagglutinin-stimulated human lymphocytes cultures from 16 healthy donors. Four conditions were studied: i) lymphocytes not exposed to the field (control cultures); ii) lymphocytes exposed to the field; iii) lymphocytes treated with mitomycin-C and not exposed to the field; iv) lymphocytes treated with mitomycin-C and exposed to the field. Mitomycin-C treated cultures were used as control for the micronucleus method, because it is known that mitomycin-C is a potent genotoxic agent, capable of inducing micronuclei. The frequency of micronuclei in field-exposed cultures was similar to the spontaneous frequency observed in control unexposed-cultures. Moreover, the exposure to pulsed magnetic fields did not affect the frequency of micronuclei induced by mitomycin-C, suggesting that, in the experimental conditions used, this kind of field neither affected the integrity of chromosomes nor interfered with the genotoxic activity of mitomycin-C. PMID- 1902103 TI - Purification of glycated hemoglobin free of hemoglobin A1c and its use to produce monoclonal antibodies specific for deoxyfructosyllysine [correction of deoxyfructosyllsine] residues in glycohemoglobin. AB - Hemoglobin nonenzymatically glycated at E-amino groups of lysine residues was purified from human erythrocyte lysates and used for immunization of BALB/c mice. Hybridomas secreting monoclonal antibodies for glycated hemoglobin were produced by fusion of mouse spleen cells with SP 2/0 myeloma cells. Immunoblotting with purified monoclonal antibody demonstrated specificity for glycated hemoglobin, with no reaction with HbAO. Glycated hemoglobin was effectively separated from other hemoglobins upon application of erythrocyte lysates to an affinity column of monoclonal antibody immobilized onto Sepharose 4B. A small fraction of purified HbA1c adsorbed to the monoclonal antibody affinity column, indicating that glycation can occur at both E-amino lysine and N-terminal valine positions in the same molecule. HbA1c did not react with the antibody after removal by immunoadsorption of molecules containing glycated lysine, confirming specificity of the antibody for deoxyfructosyl-lysine residues. The findings indicate that these monoclonal antibodies are site specific for glycated lysine amino groups in hemoglobin, and can provide rapid and efficient separation and identification of glycated hemoglobin in human erythrocyte lysates. PMID- 1902104 TI - Production of polyclonal and monoclonal antibodies for specific detection of nitrosation-proficient denitrifying bacteria in biological fluids. AB - Polyclonal and monoclonal antibodies were raised against the nitrosating enzyme previously isolated and purified from a denitrifying bacteria Pseudomonas aeruginosa. Using the polyclonal antibodies, a preliminary ELISA test was set up which allowed the detection of the nitrosating enzyme in 2 ml urine samples with a minimal total bacteria count of greater than or equal to 10(5) cells/ml. The use of such a rapid immunological screening test in clinical settings should ascertain whether individual subjects at higher risk for cancer of the stomach or bladder harbour more nitrosation-proficient microorganisms in their microflora. The availability of monoclonal antibodies provides a tool for studying the mechanisms of bacteria-mediated nitrosamine formation from precursor amines. PMID- 1902105 TI - Guanidine group specific ADP-ribosyltransferase in murine cells. AB - We have identified a guanidine group specific ADP-ribosyltransferase activity, capable of transferring an ADP-ribose group from NAD to a low molecular weight guanidine compound [p-(nitrobenzylidine)amino]guanidine and proteins such as histone and poly-L-arginine, in a variety of murine cell lines. The enzyme activity appears to be associated with an integral membrane protein of apparent molecular weight 30-33 kDa. Incubation of the viable cells in isotonic phosphate buffered saline with [32P]NAD results in the incorporation of label into cellular proteins. Dimethyl sulfoxide treatment of the cells downregulates the transferase activity as well as the ADP-ribosylation of cell proteins with extracellular NAD. PMID- 1902107 TI - Glucuronidation of mono(2-ethylhexyl)phthalate. Some enzyme characteristics and inhibition by bilirubin. AB - A method for assaying mono(2-ethylhexyl)phthalate (MEHP) uridine diphosphate (UDP) glucuronyl transferase activity in microsomal preparations from guinea pig liver is described. The quantitation of the MEHP-glucuronide was performed by HPLC after direct injection of a sample of deproteinized incubation mixture. Solubilization of microsomal UDP-glucuronyltransferase activity was achieved by use of Lubrol, and optimal conditions for glucuronidation of MEHP were established. To investigate whether there is competition between MEHP and bilirubin for glucuronidation, inhibition experiments were performed with solubilized enzyme preparations. In these incubations addition of bilirubin decreased the formation of MEHP-glucuronide. No change in the maximal conversion rate (Vmax) was observed, indicating the occurrence of competitive inhibition. This observation may have implications in clinical situations where patients with hyperbilirubinemia are exposed to MEHP, e.g. in exchange transfusions in newborn infants. PMID- 1902106 TI - Production of activin-binding protein by rat granulosa cells in vitro. AB - We have developed an assay method for activin-binding protein, which exploits its high affinity for sulfated polysaccharides. We used this method to investigate the production of activin-binding protein by rat ovarian granulosa cells, in vitro. The production of activin-binding protein by granulosa cells was dependent on the cell density; the maximum was observed at 6 x 10(5) cells/ml. Follicle stimulating hormone (FSH), but not luteinizing hormone (LH), enhanced production significantly. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS PAGE) and ligand blotting analyses of the activin-binding protein secreted by rat granulosa cells demonstrated it was the same protein molecule as that purified from rat ovaries. It is inferred from these results that the granulosa cell is a source of ovarian activin-binding protein and that its secretion is regulated by FSH. PMID- 1902109 TI - Monoaminoguanidine inhibits aldose reductase. PMID- 1902108 TI - Metabolism of 7,12-dimethylbenz[a]anthracene in hepatic microsomal membranes from rats treated with isoenzyme-selective inducers of cytochromes P450. AB - Previous work has shown that member(s) of the cytochrome P450IIC sub-family play significant roles in the formation of diols of 7,12-dimethylbenz[a]anthracene (DMBA) and are particularly important in formation of the proximate carcinogen (DMBA-3,4-diol). To further characterize the role of members of this subfamily in DMBA-diol formation and to assess the part played by other P450s, DMBA metabolism has been investigated in microsomes prepared from animals pre-treated with isoenzyme selective inducers. The rates of formation of DMBA-diols in membranes from phenobarbital-treated rats were very low when NADH was used as reductant and rates were not altered when NADPH and NADH were used in combination rather than using NADPH alone. This suggests that cytochrome b5 is not involved in DMBA-diol formation in these membranes. Treatment of animals with clofibrate, pyrazole and dexamethasone produced regio-selective alterations in the rates of formation of DMBA-diols at the -3,4-, -5,6- and -8,9- positions. However, none of the inducers caused increases in the rates of DMBA-diol formation of any great magnitude suggesting that the isoforms which are the major induced proteins (P450IVA1, P450IIE1 and P450IIIA1) do not play a significant role in diol formation. The content of other P450s in these membrane are also altered and these were investigated by Western blot using antibodies to P450IIC6, P450IIB1 and P450IIIA1. The results of the Western blots show that the effects of the inducing agents on DMBA-diol formation can be explained by alterations of members of the P450IIC and P450IIB subfamilies. PMID- 1902110 TI - Studies on the mechanism of resistance to mitomycin C and porfiromycin in a human cell strain derived from a cancer-prone individual. AB - The mechanism of aerobic resistance to the quinone-containing anti-tumour agents mitomycin C (MMC) and porfiromycin (PM) has been investigated using non transformed human cells. One of the cell strains used (3437T) was derived from an afflicted member of a cancer-prone family. This cell strain had been shown previously to be six times more resistant to the cytotoxic effects of these agents under aerobic but not hypoxic conditions when compared to a cell strain derived from an unrelated, normal donor (GM38). Differences could not be detected in the ability of cell sonicates prepared from either cell strain to produce alkylating species under aerobic conditions using a 4-(p-nitrobenzyl)pyridine assay. However, using 3H-labelled PM to monitor rapid drug uptake and subsequent accumulation due to drug metabolism, results were obtained indicating that the resistant cell strain (3437T) was deficient in an enzymatic pathway capable of metabolizing these compounds under aerobic but not hypoxic conditions. Dicumarol, an inhibitor of the quinone reductase DT-diaphorase (EC 1.6.99.2), decreased aerobic drug accumulation and cytotoxicity in the control cell strain, but did not alter the lack of accumulation noted in the resistant cell strain. Under hypoxic conditions, dicumarol increased cytotoxicity and drug accumulation in both cell strains. The mechanism of this enhanced cytotoxicity remains unclear. These results suggested that the resistant cells were deficient in the enzyme DT diaphorase, a potential activator of PM. Enzymatic assays confirmed this and revealed no alterations in cytochrome P450 reductase (EC 1.6.2.4) activity or glutathione content. No protein characteristic of DT-diaphorase was detected in the resistant cell strain using a polyclonal rabbit-anti-rat antibody raised against this enzyme. Southern blot analysis using a rat DT-diaphorase cDNA probe demonstrated differences between the normal and resistant cell strains in the restriction fragment patterns. The present results are consistent with the hypothesis that decreased DT-diaphorase levels are causally associated with PM and MMC resistance in these cells under aerobic exposure conditions. PMID- 1902111 TI - Lectin histochemistry of embryonal carcinoma. AB - Histological tissue sections of human testicular embryonal carcinoma from 13 patients and of a xenograft tumour in nude mice, as well as cell lines of human embryonal carcinoma, were investigated with eight different lectins to characterize the distribution of glycoconjugates in embryonal carcinoma. In all cases the malignant cells showed binding with Con A, WGA and RCA I conjugates, whereas other lectins were bound to some, but never to all, tumour cells in each group, revealing the heterogeneity of the malignant cells. A polarization of cancer cells was shown particularly with WGA and RCA I labelling, which was most intense on the luminal borders of the carcinoma cells, where pseudotubular structures were formed. The sugar staining properties were retained in cell culture and in the xenograft tumour. Regardless of the germ cell origin, embryonal carcinoma cells differed from normal germ cells. The distribution of glycoconjugates was also different from that of testicular carcinoma-in-situ germ cells, which share morphological features and the pattern of glycosylation with seminoma cells. However, the similarities in lectin binding pattern of seminomas and embryonal carcinomas suggest the close relationship between the two types of testicular malignancy, without excluding the possibility that embryonal carcinomas were derived from seminomas. Although lectins seem to be less important for differential diagnostic use in testicular cancer, our findings showed the usefulness of lectin histochemistry for characterization of embryonal carcinoma. PMID- 1902112 TI - [Right aortic arch with a retro-esophageal diverticulum (embryology, anatomy, classification, clinical picture, diagnosis and surgical treatment)]. AB - Five clinical cases (adult patients) are discussed in illustration of the problems of embryology, anatomy, clinical picture, and X-ray and angiographic diagnosis of a rare anomaly, right arch of the aorta (RAA) with retro-esophageal diverticulum of the aorta. According to I. J. Garti's classification, type C RAA was determined in 4 patients and type B RAA in one patient. The vascular ring around the esophagus and trachea was manifested clinically by mild respiratory disorders in 2 and marked dysphagia in all 5 patients, which required surgical correction. Four patients were operated on through a left posterolateral thoracotomy in the fourth-fifth intercostal space, one patient through a bilateral approach with division of the sternum on the level of the third intercostal space. The clinical effect of the operation was good in all patients. The indications for and the tactics of surgical treatment are discussed. PMID- 1902113 TI - An affordable approach to interactive desktop molecular modeling. AB - The amazing revolution in computer hardware performance and cost reduction has yet to be carried over to computer software. In fact, application software today is often more expensive and less reliable than the hardware. New enhancements in software development techniques, such as object oriented programming and interactive graphics based user interface design, finally may be having a significant impact on the time-to-market and reliability of these application programs. We discuss our experiences using one such set of software development tools available on the NeXT workstation and describe the effort required to port our MidasPlus molecular modeling package to the NeXT work-station. PMID- 1902115 TI - Effect of substitution of a lysyl residue that binds pyridoxal phosphate in thermostable D-amino acid aminotransferase by arginine and alanine. AB - Lys-145 of the thermostable D-amino acid aminotransferase, which binds pyridoxal phosphate, was replaced by Ala or Arg by site-directed mutagenesis. Both mutant enzymes were purified to homogeneity; their absorption spectra indicated that both mutant enzymes contained pyridoxal phosphate bound non-covalently. Even though the standard assay method did not indicate any activity with either mutant, addition of an amino donor, D-alanine, to the Arg-145 mutant enzyme led to a slow decrease in absorption at 392 nm with a concomitant increase in absorption at 333 nm. This result suggests that the enzyme was converted into the pyridoxamine phosphate form. The amount of pyruvate formed was almost equivalent to that of the reactive pyridoxal phosphate in the mutant enzyme. Thus, the Arg 145 mutant enzyme is able to catalyze slowly the half-reaction of transamination. Exogenous amines, such as methylamine, had no effect on the half-reaction with the Arg-145 mutant enzyme. In contrast, the Ala-145 mutant enzyme neither underwent the spectral change by addition of D-alanine nor catalyzed pyruvate formation, in the absence of added amine. However, the Ala-145 mutant enzyme catalyzed the half-reaction significantly in the presence of added amine. These findings suggest that a basic amino acid residue, such as lysine or arginine, is required at position 145 for catalysis of the half-reaction. The role of the exogenous amines differs with various active-site mutant enzymes. PMID- 1902114 TI - G-protein beta gamma forms: identity of beta and diversity of gamma subunits. AB - Signal-transducing G-proteins are heterotrimers composed of GTP-binding alpha subunits in association with a tightly bound complex of beta and gamma subunits. While the alpha subunits are recognized as a family of diverse structures, beta and gamma subunits have also been found as heterogeneous isoforms. To investigate the diversity and tissue specificity of the beta gamma complexes, we have examined homogeneous oligomeric G-proteins from a variety of sources. The beta and gamma subunits isolated from the major-abundance G-proteins from bovine brain, bovine retina, rabbit liver, human placenta, and human platelets were purified and subjected to biochemical and immunological analysis. Protease mapping and immune recognition revealed an identical profile for each of the two distinctly migrating beta isoforms (beta 36 and beta 35) regardless of tissue or G-protein origin. Digestion with V8 protease revealed four distinct, clearly resolved terminal fragments for beta 36 and two for beta 35. Trypsin and chymotrypsin digestion yielded numerous bands, but again each form had a unique profile with no tissue specificity. Tryptic digestion was found to be conformationally specific with the most resistant structure being the native beta gamma complex. With increasing trypsin, the complex was digested but in a pattern distinct from that for denatured beta. In contrast to the two highly homologous beta structures, examination of this set of proteins revealed at least six distinct gamma peptides. Two unique gamma peptides were found in bovine retinal Gt and three gamma peptides in samples of bovine brain derived Go/Gi. Human placental and platelet Gi samples each contained a unique gamma.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1902117 TI - High efficiency gene transfection by electroporation using a radio-frequency electric field. AB - In order to develop a safe and effective way to introduce exogenous genes into cells, we have experimented with a new method of electroporation which uses a radio-frequency (RF) electric field to permeabilize the cell membrane. This RF method has several advantages over the conventional electroporation method which uses a direct current (DC) field. We have shown that the RF electroporation method can be used to introduce marker genes into a wide variety of cell lines, including COS-M6, CV-1, CHO, 3T3 and hepatocytes, and is able to increase substantially the efficiency of gene transfection. (For example, the amount of DNA required for transfecting two million COS-M6 cells can be as low as 0.1 microgram). The transfection efficiency is shown to be affected by a number of factors, including cell type, field strength, pulse protocol and medium buffer. Because of its wide range of applications, high transfection efficiency and lack of harmful side-effect, the RF electroporation method would be particularly useful for introducing genes into human cells for gene therapy. PMID- 1902116 TI - Topological dispositions of lysine alpha 380 and lysine gamma 486 in the acetylcholine receptor from Torpedo californica. AB - The locations have been determined, with respect to the plasma membrane, of lysine alpha 380 and lysine gamma 486 in the alpha subunit and the gamma subunit, respectively, of the nicotinic acetylcholine receptor from Torpedo californica. Immunoadsorbents were constructed that recognize the carboxy terminus of the peptide GVKYIAE released by proteolytic digestion from positions 378-384 in the amino acid sequence of the alpha subunit of the acetylcholine receptor and the carboxy terminus of the peptide KYVP released by proteolytic digestion from positions 486-489 in the amino acid sequence of the gamma subunit. They were used to isolate these peptides from proteolytic digests of polypeptides from the acetylcholine receptor. Sealed vesicles containing the native acetylcholine receptor were labeled with pyridoxal phosphate and sodium [3H]-borohydride. Saponin was added to a portion of the vesicles prior to labeling to render them permeable to pyridoxal phosphate. The effect of saponin on the incorporation of pyridoxamine phosphate into lysine alpha 380 and lysine gamma 486 from the acetylcholine receptor in these vesicles was assessed with the immunoadsorbents. The peptides bound and released by the immunoadsorbents were positively identified and quantified by high-pressure liquid chromatography. Modification of lysine alpha 380 in the native acetylcholine receptor in sealed vesicles increased 5-fold in the presence of saponin, while modification of lysine gamma 486 was unaffected by the presence of saponin. The conclusions that follow from these results are that lysine alpha 380 is on the inside surface of a vesicle and lysine gamma 486 is on the outside surface.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1902118 TI - Disposition and metabolism of 2-fluoro-beta-alanine conjugates of bile acids following secretion into bile. AB - Since 2-fluoro-beta-alanine (FBAL) conjugates of bile acids (BA), the primary biliary metabolites of fluoropyrimidine (FP) drugs, have been suggested to be related to the hepatotoxicity which develops in patients receiving FP chemotherapy by intrahepatic arterial infusion (Proc. Natl. Acad. Sci. USA 84, 5439-5443, 1987), it was important to determine whether they undergo enterohepatic circulation and hence accumulate in the liver and biliary system. In initial studies, sensitivity of FBAL-BA conjugates to hydrolysis by pancreatic enzymes was examined. In subsequent in vivo studies, a model FBAL-BA conjugate, FBAL-chenodeoxycholate (FBAL-CDC), was introduced into the lumen of the small intestine of anesthetized rats with biliary fistulas to quantitate the intestinal absorption, metabolism and tissue distribution of the conjugate. The results indicated that: (1) FBAL-BA conjugates were resistant to hydrolysis by pancreatic enzymes (carboxypeptidase A, carboxypeptidase B and trypsin) and by human pancreatic juice, but were completely hydrolyzed by cholyglycine hydrolase. (2) At least one-half of the administered FBAL-CDC was deconjugated during the process of intestinal absorption, as shown by HPLC analysis of the radioactivity in portal venous blood. (3) Deconjugated FBAL or CDC was reconjugated in liver with other bile acids or amino acids (glycine and taurine), respectively, as shown by radiochromatography of bile. (4) FBAL, formed as a result of hydrolysis of FBAL-CDC, had a wide tissue distribution. In conclusion, FBAL-CDC has a rapid turnover during its enterohepatic circulation due to deconjugation in the intestine and reconjugation in the liver. PMID- 1902119 TI - The effect of pravastatin on serum cholesterol levels in hypercholesterolemic diabetic rabbits. AB - Diabetes mellitus is associated with hyperlipidemia and increased risk of atherosclerosis. A diabetic animal model has been developed to study the effect of treatment with pravastatin, a potent HMG CoA reductase inhibitor, on plasma lipoprotein levels. Hypercholesterolemia was induced in alloxan diabetic and control rabbits by feeding a diet containing 25% casein and 10% hydrogenated coconut oil for 8 weeks. Feeding the casein-coconut oil diet to the diabetic group resulted in a 5-fold increase in serum cholesterol levels, which was not statistically different from the nondiabetic group fed this diet. However, in the diabetic group, there was more cholesterol in the VLDL fraction and less in LDL as compared to the nondiabetic group. Serum triacylglycerol levels in the diabetic rabbits were variable and ranged from 58-943 mg/dl. The diabetic and nondiabetic animals were then treated with pravastatin at a dose of 10 mg/kg per day for 21 days. In the nondiabetic group, pravastatin treatment significantly lowered serum and LDL cholesterol concentrations by 28.5% (52.3 mg/dl, P less than 0.05) and 36.2% (40.7 mg/dl, P less than 0.05) respectively, relative to the placebo group. Serum and VLDL triacylglycerol levels in the nondiabetic group were also significantly decreased following pravastatin treatment. In the diabetic group, serum and LDL cholesterol levels were decreased by 37.0% (69.1 mg/dl, P less than 0.05) and 52.7% (32.1 mg/dl, P less than 0.01), respectively, relative to the diabetics given the placebo. Pravastatin treatment did not adversely affect serum glucose levels. Thus, pravastatin treatment was effective in controlling the hypercholesterolemia present in these diabetic animals. PMID- 1902120 TI - Hemostatic effect of normal platelet transfusion in severe von Willebrand disease patients. AB - Platelet von Willebrand factor (vWF) has been suggested to play an important role in the hemostatic process. Clinical and experimental data indicate that bleeding time (BT) and platelet-vessel wall interaction cannot be normalized unless the defect of platelet vWF is also corrected. We have examined the effect of normal platelet concentrate transfusion 1 hour after cryoprecipitate infusion in five type III von Willebrand disease (vWD) patients. The cryoprecipitate infusion attained normal circulating levels of ristocetin cofactor, vWF antigen, and factor VIII activity. In two patients, cryoprecipitate infusion did not modify the BT (greater than 30 minutes), whereas in the remaining three patients BT was only partially corrected (from greater than 30 to 12, 18, and 21 minutes). However, the immediate platelet transfusion completely corrected the BT in four cases, and in one case it shortened the BT to 8.30 minutes (n = 3 to 8 minutes). In the perfusion study, cryoprecipitate infusion only resulted in a slight increase in platelet deposition (surface coverage range: 2.4% to 11.3%), whereas the platelet concentrate transfusion elicited a more marked improvement (range: 8.2% to 26.4%; P less than .02 v post-cryoprecipitate). These results suggest an important in vivo role of the platelet vWF in supporting platelet-vessel wall interaction. They also give support to the occasional addition of normal platelet transfusion to the cryoprecipitate infusion for the control of serious bleeding episodes resistant to cryoprecipitate in severe vWD patients. PMID- 1902121 TI - A monoclonal antibody to factor VIII inhibits von Willebrand factor binding and thrombin cleavage. AB - To study the interaction of human factor VIII (FVIII) with its various ligands, select regions of cDNA encoding FVIII light chain were cloned into the plasmid expression vector pET3B to overproduce FVIII protein fragments in the bacterium Escherichia coli. Partially purified FVIII protein fragments were used to produce monoclonal antibodies. One monoclonal antibody, 60-B, bound both an FVIII protein fragment (amino acid residues 1563 through 1909) and recombinant human FVIII, but not porcine FVIII. This antibody prevented FVIII-vWF binding and acted as an inhibitor in both the activated partial thromboplastin time (APTT) assay and a chromogenic substrate assay that measured factor Xa generation. The ability of the antibody to inhibit FVIII activity was diminished in a dose-dependent fashion by von Willebrand factor. This anti-FVIII monoclonal antibody bound to a synthetic peptide, K E D F D I Y D E D E, equivalent to FVIII amino acid residues 1674 through 1684. The 60-B antibody did not react with a peptide in which the aspartic acid residue at 1681 (underlined) was changed to a glycine, which is the amino acid present at this position in porcine FVIII. Gel electrophoretic analysis of thrombin cleavage patterns of human FVIII showed that the 60-B antibody prevented thrombin cleavage at light chain residue 1689. The coagulant inhibitory activity of the 60-B antibody may be due, in part, to the prevention of thrombin activation of FVIII light chain. PMID- 1902122 TI - Genomic organization of IgH gene compared with the expression of Bcl-2 gene in t(14;18)-positive lymphoma. AB - In three lymphoma cell lines carrying t(14;18), named FL-18, FL-218, and FL-318, the genomic organization of IgH gene was compared with the expression of bcl-2 gene; the t(14;18) of the FL-18 cells occurred downstream from the major breakpoint cluster region (mbr) of a bcl-2 gene, and that of the FL-218 and FL 318 cells within the mbr. The FL-318 expressed the normal-sized bcl-2 transcript of 8.5-kb mRNA having the noncoding region 3 to the mbr, which was found in the FL-18, and the FL-218 lacking the intact bcl-2 gene did not. This finding suggests that in t(14;18)-positive lymphoma having the breakpoint within the mbr, transcription of the nontranslocated bcl-2 allele is not necessarily silent. In addition, the FL-218 and FL-318 expressed aberrant bcl-2 transcripts and heterogenous IgH transcripts lacking the VH region, and the bcl-2 transcripts each comigrated with parts of the sterile IgH mRNAs. The FL-318, which did not exhibit switch recombination on either IgH allele, contained abundant amounts of l gamma mRNAs, a prerequisite for the recombination into the C gamma locus. One of the I-mRNA species comigrated with the aberrant bcl-2 transcript. The FL-18 and FL-218 lacking the I gamma mRNAs had completed switch recombination of both IgH alleles. This result raises a possibility that deregulated bcl-2 transcription caused by t(14;18) is capable of playing a role in class switch recombination of IgH gene. PMID- 1902123 TI - Expression of shared idiotypes in chronic lymphocytic leukemia and small lymphocytic lymphoma. AB - The expression of shared idiotypes (Slds) has been studied on malignant CD5+B cells from patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) using a panel of 37 murine monoclonal antibodies previously demonstrated to be reactive with Slds derived from follicular B-cell lymphomas. Thirteen anti-Slds identified tumor cells from 31 of 105 (30%) CLL patients and 4 of 6 SLL patients. In comparison, the same panel of anti-Slds is reactive with 33% of follicular and diffuse B-cell lymphomas. Ten of these anti-Slds reacted with CLL cases at similar frequencies to that of the B-cell lymphomas. Two anti Slds, which are known to react with autoantibodies, were significantly more prevalent in CLL than in B-cell lymphomas. These data confirm the presence of Slds in CLL and provide further evidence of an association between CLL and autoimmunity. The identification of a panel of antibodies reactive with a significant number of CLL and SLL patients will facilitate the application of anti-idiotype antibody therapy in these diseases. PMID- 1902124 TI - Cell-type specificity of interferon-gamma-mediated HLA class I gene transcription in human hematopoietic tumor cells. AB - Major histocompatibility complex class I gene expression plays a central role in cellular immunity and tumor surveillance. A substantial proportion of spontaneous tumors are class I-deficient and numerous experiments have suggested that alterations in class I expression may alter oncogenicity and, as a result, have potential therapeutic impact. Interferons (IFNs) are able to upregulate class I expression by mechanisms that remain to be elucidated, but which appear to be IFN and cell-type specific. We have characterized in detail the in vivo class I transcriptional response to IFN-gamma in two human hematopoietic tumor cell lines, the class I-deficient K562 cell line and the class I-positive Ramos cell line. In each, IFN-gamma induces a rapid increase in class I transcription, which is sustained in Ramos cells, but transient in K562 cells. In each, stimulation by IFN-gamma is dependent on ongoing protein synthesis, suggesting the requirement for production of a "primary response" protein. These data suggest that more than one type of IFN-gamma-induced signal is operative in the transcriptional response to IFN-gamma. Cycloheximide alone is also capable of inducing a rapid increase in class I transcription in both cell types, suggesting that constitutive attenuation of class I transcription may be a common phenomenon, and that IFN gamma may act, in part, by interfering with such attenuation. PMID- 1902125 TI - Phase I/II trial of recombinant human granulocyte-macrophage colony-stimulating factor following allogeneic bone marrow transplantation. AB - Forty-seven patients with hematologic neoplasia received recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) by daily 2-hour infusion following allogeneic bone marrow transplantation from HLA-identical sibling donors in a phase I-II dose-escalation trial. Dose levels ranged from 30 to 500 micrograms/m2/d. At doses at or below 250 micrograms/m2/d, toxicity felt to be caused by rhGM-CSF was negligible. However, three of five patients treated with 500 micrograms/m2/d had unacceptable side effects caused by rhGM-CSF. Two different graft-versus-host disease (GVHD) prophylactic regimens were administered. Twenty-seven evaluable patients were administered regimens that did not contain methotrexate (MTX) (Group I) and reached an absolute neutrophil count of 1,000/microL by a median of day 14. In contrast, 18 patients who received GVHD prophylactic regimens containing MTX (Group II) reached an absolute neutrophil count of 1,000/microL on a median of day 20. Patients in Group I had fewer febrile days and, of those discharged, had shorter initial hospitalizations than patients in Group II. The overall incidence of severe acute GVHD (grade 2 or greater) in the rhGM-CSF-treated patients was 28% and was similar to that in historical "good risk" patients who did not receive rhGM-CSF. These preliminary data suggest rhGM-CSF is unlikely to exacerbate GVHD in HLA-identical sibling donor transplants and indicate the need for randomized trials of rhGM-CSF in allogeneic marrow transplant patients. PMID- 1902126 TI - Induction of neutrophil FC-gamma receptor I expression can be used as a marker for biologic activity of recombinant interferon-gamma in vivo. PMID- 1902127 TI - Calcium and the malaria parasite: parasite maturation and the loss of red cell deformability. AB - In the studies reported here, we examined the role of calcium in the maturation of the human malaria parasite Plasmodium falciparum, and in the loss of red cell deformability associated with parasite maturation. P. falciparum alters the permeability of its host red cell, which normally maintains submicromolar cytoplasmic concentrations of calcium. Infection of the red cell and parasite maturation produce a 30-fold increase in calcium uptake. Both parasite maturation and the loss of red cell deformability are blocked by EGTA (by extracellular-free calcium concentrations less than or equal to 35 microM) and by other calcium antagonists. The loss of red cell deformability that occurs with parasite maturation is accompanied by alterations in the cytoskeletal proteins of parasitized red cells similar to those produced by the calcium ionophore A23187 (reductions in bands 2.1 [ankyrin], 4.1, and 5 [actin]). These results establish that parasite development and the loss of red cell deformability are calcium dependent. They suggest that parasite-induced changes in the calcium permeability of the red cell activate endogenous transglutaminase activity by raising the free calcium concentration of the red cell cytoplasm. PMID- 1902128 TI - Acute toxicity of PCB congeners to Daphnia magna and Pimephales promelas. PMID- 1902129 TI - Growth response of freshwater algae, Anabaena flos-aquae and Selenastrum capricornutum to atrazine and hexazinone herbicides. PMID- 1902131 TI - Accumulation factors for eleven polychlorinated biphenyl congeners. PMID- 1902132 TI - Home enteral nutrition in paediatric practice. AB - Nasogastric feeding at home is increasingly being used to provide nutritional support for children with chronic conditions associated with poor growth. The development of specialized feeding products together with accurate and portable enteral feeding pumps has facilitated this process. Parents manage home nasogastric feeding well but require education and continued support. This is probably best offered by a specialized multidisciplinary nutritional care team. PMID- 1902133 TI - Modulation of vocal and nonvocal behavior in adult squirrel monkeys by selective MAO-A and MAO-B inhibition. AB - The acute effects of monoamine oxidase inhibitors L-deprenyl (0.5-5.0 mg/kg), clorgyline (1.0-10.0 mg/kg), and milacemide (100-400 mg/kg) on the behavior of adult male squirrel monkeys were examined during brief social separations beginning 60 min after subcutaneous drug administration. All three drugs selectively reduced the rate of calling during social separation at doses which did not affect time spent in locomotion, nor the frequency of vigilance-checking. Deprenyl and milacemide, but not clorgyline, produced concurrent decreases in locomotion at the higher doses tested. At threshold doses, clorgyline, but not deprenyl or milacemide, increased call duration and decreased call peak frequency compared to vehicle control values. Plasma levels of MHPG were decreased by an optimal dose of clorgyline but not by deprenyl or milacemide, indicating that substrate specificity was maintained at the drug doses employed. We conclude that different MAO substrates mediate different aspects of vocal and nonvocal behavior in adult male squirrel monkeys. PMID- 1902130 TI - Effects of paraquat and lead on fish Oreochromis hornorum. PMID- 1902134 TI - Cancer risk and extremely low frequency electromagnetic radiation. PMID- 1902135 TI - Unproven methods of cancer management. Livingston-Wheeler therapy. AB - Livingston-Wheeler's cancer treatment is based on the belief that cancer is caused by a bacterium she has named Progenitor cryptocides. Careful research using modern techniques, however, has shown that there is no such organism and that Livingston-Wheeler has apparently mistaken several different types of bacteria, both rare and common, for a unique microbe. In spite of diligent research to isolate a cancer-causing microorganism, none has been found. Similarly, Livingston-Wheeler's autologous vaccine cannot be considered an effective treatment for cancer. While many oncologists have expressed the hope that someday a vaccine will be developed against cancer, the cause(s) of cancer must be determined before research can be directed toward developing a vaccine. The rationale for other facets of the Livingston-Wheeler cancer therapy is similarly faulty. No evidence supports her contention that cancer results from a defective immune system, that a whole-foods diet restores immune system deficiencies, that abscisic acid slows tumor growth, or that cancer is transmitted to humans by chickens. PMID- 1902136 TI - The slowing of the lung cancer epidemic and the need for continued vigilance. PMID- 1902137 TI - The epidemiology of breast cancer. AB - Table 5 presents risk factors for breast cancer generally regarded as established, together with their approximate relative risks. With the exception of age, country of birth, and a history of breast cancer in both a mother and a sister, all of the relative risks reported to date are of a relatively modest magnitude. Thus, new risk factors need to be identified and knowledge of existing risk factors refined. Factors for which the evidence of an etiologic role has mounted over the past several years, but which are not yet considered to be established, include the protective effects of parity and lactation in certain age groups and the increased risks associated with alcohol consumption and with DES exposure during pregnancy. In addition, physical activity has emerged as a factor worthy of further study. Some evidence suggests that use of oral contraceptives for several years at an early age modestly increases the risk for breast cancer diagnosed before age 35 and perhaps age 45. Use of estrogen replacement therapy for 20 years or more has been found by a few studies to increase the risk for breast cancer in the postmenopausal years; further studies of very long-term users are needed. Also, other risks and benefits of these hormones need to be taken into account when women decide whether to use them. Surprisingly elusive has been the etiologic role of endogenous hormones, especially in view of the large number of studies that have been concerned with them. A better understanding of the role of endogenous hormones should help explain the mechanisms of action of known and suspected risk factors. Areas of high priority for further research thus include establishing with more certainty whether the risk for breast cancer is increased in any subgroups of women who use oral contraceptives and estrogen-replacement therapy and determining the etiologic roles of specific endogenous hormones. The possible risks associated with alcohol consumption and lack of physical activity need to be studied more thoroughly, and ideas about new potential risk factors are needed. Although epidemiologic studies will continue to be concerned with diet, enthusiasm for its etiologic role in women has been considerably dampened by the lack of association in many of the studies reported to date. The studies in women exposed to radiation, DES, and oral contraceptives suggest that the timing of some exposures may be critical, since the effects of these agents may mostly be limited to specific time periods of rapid breast development.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1902138 TI - Malignant effusions. PMID- 1902139 TI - The ethics of randomization. PMID- 1902140 TI - Unproven methods of cancer management. Laetrile. AB - "Laetrile" is used interchangeably with "amygdalin" to designate natural substances, derived primarily from apricots and almonds, that can release cyanide, which is lethal to living organisms. In the 1920s, Dr. Ernst T. Krebs, Sr., formulated a theory that amygdalin could kill cancer cells. His theory was inconsistent with biochemical facts and has since been modified at least twice by his son, Ernst T. Krebs, Jr. Extensive work has been done by cancer scientists to test the claim that Laetrile fights cancer. Many animal experiments in the 1970s showed a complete lack of tumor killing by Laetrile. Reviews of the medical records of patients whose cancers were claimed to be reduced or cured after Laetrile treatment found insufficient medical evidence to judge Laetrile's efficacy. Finally, in a clinical trial in cancer patients reported in 1982, Laetrile neither caused shrinkage of tumors, nor increased survival time, nor alleviated cancer symptoms, nor enhanced well-being. Several reports in the medical literature document instances in which Laetrile has caused serious, life threatening toxicity when taken in large doses in the manner prescribed by Laetrile advocates. In light of the lack of efficacy of Laetrile and its demonstrated ability to cause harm, Laetrile should not be used to treat cancer. PMID- 1902141 TI - Tailoring total parenteral nutrition. PMID- 1902142 TI - A protein-conducting channel in the endoplasmic reticulum. AB - The existence of a protein-conducting channel in the endoplasmic reticulum membrane was demonstrated by electrophysiological techniques. Pancreatic rough microsome (RM) vesicles were fused to one side (cis) of a planar lipid bilayer separating two aqueous compartments of 50 mM salt. This exposed the cytoplasmic surface of the RMs, with its attached ribosomes, to the cis chamber. Addition of 100 microM puromycin to the cis side caused a large increase in membrane conductance, presumably the result of puromycin-induced clearance of nascent protein chains from the lumen of protein-conducting channels. When puromycin was added at low concentrations (0.33 microM), single channels of 220 pS were observed. These closed when the salt concentration was raised to levels at which ribosomes detach from the membrane (150-400 mM), indicating that the attached ribosome keeps the channel in an open conformation. A mechanism for a complete cycle of opening and closing of the protein-conducting channel is suggested. PMID- 1902143 TI - The wheat mitochondrial gene for subunit I of the NADH dehydrogenase complex: a trans-splicing model for this gene-in-pieces. AB - The nad1 gene encoding subunit I of the respiratory chain NADH dehydrogenase is fragmented into five unique-copy coding segments that are scattered over at least 40 kb and interspersed with other genes in the wheat mitochondrial genome. The nad1 segments are flanked by sequences with group II intron features, and transcript analysis demonstrates the presence of correctly spliced mRNAs. RNA editing occurs at sites asymmetrically distributed along the wheat nad1 coding region, and the initiation codon is created by RNA editing. The unusual organization of the wheat nad1 gene is attributed to mitochondrial DNA rearrangements within introns, and a trans-splicing model involving secondary structural interactions between group II-like intron pieces is proposed for its expression. PMID- 1902144 TI - Characterization of the progeny of pre-T cells maintained in vitro by IL-3: appearance in the periphery and V beta utilization in vivo. AB - We have recently demonstrated that bone marrow-resident cells, which are able to repopulate the thymus of irradiated recipient mice (pre-T cells), can be maintained in vitro for at least 2 weeks in the presence of exogenous IL-3. Because this marrow culture system can be applied to the study of early T cell differentiation, it is important to ascertain the extent to which in vitro culture of the pre-T cells might alter the T cell progeny which can develop from them. In previous work, we showed that the progeny of cultured pre-T cells appeared to develop in a kinetically normal fashion within the thymus of recipients and that the acquisition of key developmental markers (IL-2R and CD3) was identical in the progeny of fresh and cultured pre-T cells. Here, we report the results of experiments carried out to characterize the progeny of cultured pre-T cells which were found in the peripheral lymphoid tissues several weeks following intrathymic transfer to irradiated recipients. We found no remarkable differences between the progeny of cultured or fresh marrow cells with respect to the timing of their appearance in the periphery nor their expression of CD4 or CD8. By studying the patterns of utilization of five different V beta gene products by the T cells derived from fresh or cultured bone marrow, we were able to test the susceptibility of both sets of progeny to both positive and negative selection pressures during their in vivo maturation. These experiments established that the progeny of cultured marrow cells were equally susceptible to TCR repertoire selection, as were the progeny of fresh bone marrow cells, and that the process of in vitro growth did not alter the potential TCR repertoire of the pre-T cells. PMID- 1902145 TI - Inhibition of macrophage-induced antigen-specific T lymphocyte proliferation by poly I:C: strain and antigen independence. AB - We have previously demonstrated that IFN-alpha/beta, poly I:C (an inducer of IFN alpha/beta), and IFN-gamma can inhibit the ability of KLH-pulsed peritoneal macrophages to induce proliferation of syngeneic, KLH immune T lymphocytes in CBA/J mice. In this study, we show that this IFN-induced immunosuppression is not restricted to CBA/J (H-2k) mice but is also seen in BALB/cJ (H-2d) mice. A similar inhibition of proliferation is observed with the KLH-specific T cell hybridoma BDK, 100, which requires KLH-pulsed macrophages for optimum proliferation and IL-2 production. The immunosuppression produced by IFN was also independent of the antigen employed. Inhibition of T lymphocyte proliferation was observed when casein, instead of KLH, was used to immunize T cells and to pulse peritoneal macrophages in vivo. Utilizing KLH and casein, the antigen specificity of the inhibition was demonstrated. Therefore, the inhibition by the IFN-inducer poly I:C of macrophage-induced, antigen-specific T cell proliferation is not limited by H-2 type of the mice or to one antigen. PMID- 1902146 TI - Functional heterogeneity of CD4-positive T-cell subsets: the correlation between effector functions and lymphokine secretion is limited. AB - Several effector functions and the lymphokine secretion pattern of 30 antigen specific CD4+ T-cell clones have been investigated. The clones were generated directly by limiting dilution cloning of nylon wool-purified T-cells obtained from KLH immunized BALB/c mice and avoiding an initial bulk culture phase. Using this approach the CD4+ T-cell clones were grouped into helper and nonhelper subsets. Among the helper subset, clones which helped B-cells for specific antibody production by either cognate or noncognate recognition were identified. Some but not all of these helper clones fitted into the Th1 and Th2 scheme, if the lymphokine secretion pattern was evaluated. Among the nonhelper subset CD4+ clones which killed activated APC in a MHC class II-restricted and antigen specific manner were identified. In addition, one clone which suppressed B-cell antibody production mediated by helper clones was found. However, neither the suppression of antibody responses nor the inability of the nonhelper clones to help B-cells is due to the killing of B-cells. Various attempts were made to convert nonhelper into helper clones and helper into killer clones, without success. Thus, the functional properties of these clones are stable traits and not convertible by varying the experimental conditions. PMID- 1902147 TI - IFN-gamma enhances secretion of IgG2a from IgG2a-committed LPS-stimulated murine B cells: implications for the role of IFN-gamma in class switching. AB - IFN-gamma is a pleiotropic lymphokine that influences the isotypes of immunoglobulin secreted by B cells. IFN-gamma inhibits the secretion of IgG3, IgG2b, IgG1, and IgE, and enhances the secretion of IgG2a. We have examined the mechanism of IFN-gamma-mediated enhancement of IgG2a secretion in sorted populations of B cells and find that IFN-gamma reproducibly stimulates a twofold increase in the precursor frequency of IgG2a-secreting cells in the sIgG2a+ population. Additionally, we find that IFN-gamma does not induce an increase in the clone size of IgG2a-secreting cells. IFN-gamma stimulates a twofold increase in the precursor frequency of IgG2a-secreting cells from sIgG- and unsorted B cells which can be attributed to an increase in IgG2a secretion from IgG2a committed cells in these populations. Hence, under the culture conditions utilized in these studies. IFN-gamma enhances IgG2a secretion from IgG2a committed cells and does not induce a class switch. PMID- 1902148 TI - Amiloride delays the ischemia-induced rise in cytosolic free calcium. AB - An increase in cytosolic free calcium (Cai) has been shown to occur early during ischemia in perfused rat, ferret, and rabbit hearts. It has been proposed that this increase in Cai may occur as a result of exchange of Nai for Cao, which occurs as a result of an increase in Nai arising from exchange of Nao for H+i. The latter exchange is stimulated by the intracellular acidification that occurs during ischemia. To test this hypothesis, we examined Cai, Nai, ATP, and pHi during ischemia in rats in the presence and absence of 1 mM amiloride, a Na-H exchange inhibitor. Cai was measured using 19F nuclear magnetic resonance (NMR) of 1,2-bis(2-amino-5-fluorophenoxy)ethane-N,N,N',N'-tetra-acetic acid (5F-BAPTA) loaded rat hearts. Nai was measured using 23Na NMR, and the shift reagent 1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetramethylenephosph onate (Tm[DOTP] 5) was used to separate Nai and Nao. ATP and pH were determined from 31P NMR measurements. During 20 minutes of ischemia, amiloride did not significantly alter the ATP decline but did significantly attenuate the rise in Nai and Cai. After 20 minutes of ischemia, time-averaged Cai was 1.0 +/- 0.2 microM (mean +/- SEM) in amiloride-treated hearts compared with 2.3 +/- 0.9 microM in nontreated hearts. After 20 minutes of ischemia, Nai in the untreated heart was threefold greater than control, whereas in the amiloride-treated heart, Nai was not significantly different from control. These data are consistent with the involvement of Na-Ca exchange in the rise in Cai during ischemia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1902149 TI - Differences in prostaglandin metabolism in cultured aortic and pulmonary arterial endothelial cells exposed to acute and chronic hypoxia. AB - In vivo, a marked difference in blood oxygen tension exists between the pulmonary artery and the aorta. Responses of vascular endothelial cells from these vessels to changes in ambient oxygen might be influenced by the oxygen tension to which they are continuously exposed in vivo or by their anatomic site. To explore this hypothesis, we initially studied the production of the cyclooxygenase metabolites prostacyclin and thromboxane in bovine aortic and main pulmonary arterial endothelial cells grown in 21% O2 and exposed to different degrees of acute hypoxia over a wide range of times. We found that short-term hypoxia (3% or 0% O2) rapidly and transiently activates the cyclooxygenase pathway in both cell types, with a more rapid response in bovine aortic endothelial cells. To determine whether culture in an oxygen tension similar to that to which main pulmonary arterial endothelial cells are exposed in vivo alters this response, we evaluated these cyclooxygenase metabolites in bovine aortic and main pulmonary arterial endothelial cells cultured long-term in 3% O2, both at baseline and after exposure to acute anoxia (0% O2). In both cell types, we found a decrease in prostacyclin and thromboxane synthesis at baseline and evidence of an increase in the Vmax of thromboxane synthetase following stimulation with exogenous arachidonic acid. In chronically hypoxic cells exposed to acute anoxia, there were marked differences in enzyme activity compared with that in endothelial cells maintained in 21% O2 with differences depending on the origin of the endothelial cells. In bovine aortic endothelial cells, production of neither cyclooxygenase metabolite increased; in bovine main pulmonary arterial endothelial cells, only thromboxane production increased, suggesting isolated activation of the cyclooxygenase-thromboxane synthetase pathway. These studies demonstrate that acute and chronic hypoxia have profound effects on endothelial cell cyclooxygenase metabolism and that these effects depend on the duration and degree of the hypoxic exposure and the vascular bed from which the endothelial cells are derived. PMID- 1902150 TI - Management of acute myocardial infarction 1990: a perspective. AB - Rising costs have reached a point at which physicians must assume a major role in dealing with the cost of medicine. Little information is available regarding actual practice at the community hospital level. In order to develop some insight on this issue, a survey of cardiovascular specialists was conducted regarding management of acute myocardial infarction in 1990. The results indicate a major lack of correlation between efficacy, cost, and practice patterns in terms of current knowledge. Perhaps legal concerns have contributed to these current practice patterns. Clearly, aside from choice of thrombolytic agent and/or PTCA, early treatment of acute myocardial infarction has emerged as a most important factor in reducing mortality. PMID- 1902151 TI - Comparison of bovine collagen xenografts to autografts in the rabbit. AB - The use of bovine tendon as a xenograft material in humans is attractive because of its ready availability and favorable mechanical characteristics. Previous research has shown that the fibroblasts and some extracellular proteoglycans and glycoproteins, not the collagen matrix itself, in bovine tendon are primarily responsible for its antigenicity. Various attempts have been made to decrease the antigenicity of these grafts. A chloroform/methanol (CM) extraction procedure has been developed that selectively removes the fibroblasts from bovine tendon without destroying the collagen matrix. The mechanical, immunologic, and local host tissue responses to these grafts were compared to autografts and to untreated and glutaraldehyde-treated bovine tendon xenografts. The humoral immune response to a purified bovine Type I collagen product was also studied. The central two-thirds of a rabbit Achilles tendon were replaced with a reversed autograft or an experimental graft. Histologic examination of one- and two- week specimens showed an acute inflammatory response to all grafts. Untreated grafts stimulated a severe inflammatory response and were almost completely resorbed by two weeks. Glutaraldehyde-treated grafts were encapsulated. Cellular repopulation was minimal and inflammatory response was more persistent than in the autograft and CM groups. Inflammatory response to CM-treated grafts was similar to that of autografts. The CM grafts repopulated rapidly with host cells. The mechanical strength of CM grafts was equal to autograft controls at 12 weeks. The mechanical strength of untreated and glutaraldehyde-treated grafts was significantly lower. Measurement of the humoral immune response to these grafts was conducted in an independent group of animals using an enzyme-linked immunosorbent assay. A significant antibody response to untreated, glutaraldehyde-fixed, and CM-treated grafts was detected at 30 days. Antibody titers to glutaraldehyde-fixed and untreated grafts remained elevated at 60 and 90 days. In the CM group, antibody titers decreased to the level of autograft controls by 90 days. No significant antibody response was detected toward purified bovine Type I collagen. PMID- 1902152 TI - The efficacy of topical ciprofloxacin and norfloxacin in the treatment of experimental Pseudomonas keratitis. AB - An aminoglycoside-resistant strain of Pseudomonas aeruginosa was injected intrastromally into the corneas of rabbits, and keratitis was allowed to develop over a 22-h period. Rabbits were treated with either 0.75% ciprofloxacin, 1% norfloxacin, or 1.36% tobramycin administered topically every 15 min for 1 h and then every 30 min for the following 3 h. All therapy ceased 26 h postinoculation. Rabbits were killed 1 h after the treatment, and the number of bacteria per cornea were quantified in terms of bacterial colony-forming units. Aqueous humor specimens were obtained from rabbits receiving norfloxacin and ciprofloxacin, and bioassays were performed to determine drug concentration. Ciprofloxacin caused a 5 log reduction in the number of bacterial colony-forming units, as compared with untreated controls (p less than 0.0001); it also produced a significantly greater reduction in bacterial colony-forming units than either norfloxacin or fortified tobramycin drops (p less than 0.0001). Norfloxacin produced a 2 log reduction in bacterial colony-forming units, as compared with untreated controls (p less than 0.0001). The mean aqueous concentration of norfloxacin (7.5 micrograms/ml) was substantially less than that achieved by ciprofloxacin (30.5 micrograms/ml). We conclude that ciprofloxacin may be a useful broad spectrum, topical chemotherapeutic agent in the therapy of aminoglycoside-resistant P. aeruginosa keratitis. PMID- 1902153 TI - Microfilaments, microtubules, and intermediate filaments in cultured corneal fibroblasts. AB - Corneal stromal fibroblasts play an important role in wound healing. Proteins from all three cytoskeletal classes (microfilament, microtubule, and intermediate filament) are involved in the control of various cellular events, such as motility, cell adhesion, shape changes, intracellular transport, and mitosis. By epifluorescent light microscopy, we studied the intracellular distributions of actin (microfilament), tubulin (microtubule), and vimentin (intermediate filament), as well as vinculin (a junctional protein connecting microfilaments to the cell membrane), in cultured corneal fibroblasts. Mutual positional relationships between actin and the other cytoskeletal proteins were investigated by double-labeling. Particular attention was paid to the leading edge of spreading or migrating fibroblasts and to their cell-to-cell contacts. PMID- 1902154 TI - Clinical utility and cost-effectiveness of protective sleeve pulmonary artery catheters. AB - OBJECTIVE: To assess the clinical utility of protective sleeves in pulmonary artery (PA) balloon flotation catheters. DESIGN: Prospective, randomized trial with cost-effectiveness analysis. SETTING: A general adult ICU in a community teaching hospital. PATIENTS: All patients receiving PA balloon flotation catheters over a 1-yr period. INTERVENTIONS: Groups 1 and 2 received PA catheters with and without protective sleeves, respectively. Indications for catheter changes, other than catheter malposition, were the same for both groups. MEASUREMENTS AND MAIN RESULTS: In group 1, 54 patients received 71 catheters and four catheters were replaced due to the inability to obtain a PA occlusion pressure (PAOP) tracing. In group 2, 48 patients received 66 catheters, 11 of which were inserted due to failure to obtain a PAOP (p less than .05). PA catheters were repositioned successfully in 37/56 attempts in group 1, compared with 8/20 attempts in group 2 (p less than .05). There was no significant difference in complication rates between the two groups. Even at the increased cost of the protective sleeves and introducer ($7/kit), for 100 catheter insertions, we project a direct cost savings of $742, and personnel time savings of 10.5 hrs for physicians, 14 hrs for nurses, and 4.7 hrs for radiology technicians. CONCLUSION: Protective sleeves on PA catheters are safe, effective, cost-saving devices for ICU patients. PMID- 1902155 TI - Acid-base derangements during sorbent regenerative hemodialysis in mechanically ventilated patients. AB - OBJECTIVE: To assess acid-base derangements during sorbent regenerative hemodialysis in mechanically ventilated patients. DESIGN: Consecutive case series; prospective study. SETTING: An ICU in a university hospital. PATIENTS: Seven patients undergoing hemodialysis for acute renal failure who required mechanical ventilation for acute respiratory failure. INTERVENTIONS: Pulmonary and systemic hemodynamics, pH, and gas tensions in dialysate, arterial and mixed venous blood, and blood entering and leaving the dialyzer, were measured before, during, and after hemodialysis. MEASUREMENTS AND MAIN RESULTS: During the first 2 hrs of hemodialysis, dialysate pH decreased from 6.91 +/- 0.14 to 6.06 +/- 0.37 and PCO2 increased to 437 +/- 111 torr (58.2 +/- 14.8 kPa). Simultaneously, the patients lost bicarbonate into the bath. As a result, pHa decreased from 7.38 +/- 0.02 to 7.31 +/- 0.02. At the end of dialysis, pHa returned to normal. CONCLUSION: Sorbent hemodialysis in mechanically ventilated patients is accompanied by acidosis that may contribute to hemodynamic instability. PMID- 1902156 TI - Validity of a disposable end-tidal carbon dioxide detector in verifying endotracheal tube position in piglets. AB - BACKGROUND AND METHODS: the most reliable methods for confirming endotracheal tube placement are direct visualization of passage through the vocal cords and documentation of CO2 in the expired gas. We evaluated the use of a disposable colorimetric CO2 detector for verifying endotracheal tube position in small animals. The end-tidal CO2 (Petco2) detector was tested in 11 piglets with the endotracheal tube sequentially in the trachea, the esophagus, the esophagus with a carbonated beverage in the stomach, the esophagus after bag-mask ventilation. Endotracheal tube position was confirmed in all cases by direct visualization and capnometry. RESULTS: The Petco2 detector identified the tube placement accurately in all 54 (21 tracheal, 33 esophageal) intubations (p less than .001). CONCLUSIONS: This disposable Petco2 detector is highly sensitive and specific for verifying endotracheal tube placement in this nonarrest piglet model. PMID- 1902157 TI - Are changes in venous-arterial carbon dioxide tension gradient and cardiac output linearly related? PMID- 1902158 TI - Cytokine content in pleural effusion. Comparison between tuberculous and carcinomatous pleurisy. AB - Tuberculous pleurisy is a good model for resolution of local cellular immunity. It would be expected that tuberculous pleural fluid contains a variety of immunologically important cytokines because of the accumulation of immunocompetent cells in the pleural cavity. We studied interleukin 1 (IL-1), interleukin 2 (IL-2), and interferon gamma (IFN-gamma) levels in pleural fluid of 20 patients with tuberculous pleurisy and compared them with those in pleural fluid of 20 patients with malignant pleurisy. We also evaluated adenosine deaminase (ADA) levels in both effusions. Tuberculous pleural fluid had higher levels of IL-1, IL-2, IFN-gamma, and ADA than malignant pleural fluid. Although the difference of IL-1 level between tuberculous and malignant pleural fluid was modest, that of IL-2, IFN-gamma, and ADA was dominant. These findings suggest that activated T lymphocytes in tuberculous pleural fluid concern the production of lymphokines at the morbid site and they effectively exert local cellular immunity through the action of such lymphokines. PMID- 1902159 TI - The day-long antianginal effectiveness of nitroglycerin patches. A double-blind study using dose-titration. AB - This study was designed to determine the day-long antianginal effectiveness of nitroglycerin patches in the nitrate-exposed patient, as well as the doses required. Eight men with chronic stable angina, a positive treadmill test, and demonstrated responsiveness to long-term oral isosorbide dinitrate were studied after they had been taking effective doses of isosorbide dinitrate three times a day for at least two weeks. Treadmill exercise bouts were performed every 1 to 2 hours over 1 day, after the 8 am application of active nitroglycerin patches in a previously titrated dose, and on another day after application of placebo patches. Mean necessary effective patch dose was 125 sq cm (60 to 220 sq cm). Mean exercise duration to angina rose from 271 to 480 s (p less than 0.001) 1 hour after active patches, while resting systolic blood pressure fell from 122 mm Hg to 100 mm Hg (p less than 0.001). (After placebo patches: +19 s and -2 mm Hg, respectively.) Active patches were superior to placebo throughout the day, but in declining degree (by 94 s at 7 pm, p less than 0.05). Thus, nitroglycerin patches can provide a significant day-long antianginal effect in the patient with long term exposure to nitrate. However, the need for large doses and individual titration may make this therapy impractical. PMID- 1902160 TI - Transition from exercise to rest. Ventilatory and arterial blood gas responses. AB - The mechanisms leading to rapid changes in arterial blood gas values soon after exercise ends have not been well established. To further study these phenomena, we exercised seven normal male volunteers to exhaustion on a cycle ergometer with a 25-W/min ramped protocol measuring arterial blood gas values, and breath-by breath gas exchange from rest to exercise and through 15 minutes of recovery. Arterial PO2 (PaO2) increased from 108 mm Hg at peak exercise to 125 mm Hg at 2 minutes of recovery. There was a smaller rise in calculated alveolar PO2 (PAO2) from 121 to 128 mm Hg over the same period. Arterial PCO2 (PaCO2) fell from 35.0 mm Hg to 31.9 mm Hg. The gas exchange ratio R rose from 1.21 to 1.52, after having peaked at 1.68 at 1 minute. The alveolar-arterial O2 gradient (P[A-a]O2) fell from 12.3 mm Hg at peak exercise to 3.2 mm Hg at 2 minutes. Following exercise, the rise in R is related to a more rapid fall in O2 uptake than in CO2 output, and the fall in P(A-a)O2 is probably related to improved V/Q relationships and to a rise in mixed venous PO2. We conclude that the rise in PaO2 in the recovery period after progressive nonsteady state exercise is due to several factors, including a fall in P(A-a)O2 and a rise in PAO2 due primarily to an elevation of R and also to a fall in PaCO2. PMID- 1902161 TI - Treatment of superior vena cava thrombosis with recombinant tissue type plasminogen activator. AB - Thrombotic occlusion of the superior vena cava is an uncommon but serious complication of chronic indwelling venous catheters. Several reports have shown thrombolytic therapy with intravenous streptokinase or urokinase to be effective in the treatment of this condition. We report a case of superior vena cava thrombosis in a 53-year-old woman receiving chemotherapy for breast carcinoma through a subcutaneously implanted venous access catheter who was successfully treated with peripheral infusion of recombinant tissue type plasminogen activator (rtPA). PMID- 1902162 TI - [Papillary thyroid carcinoma in a median ectopic thyroid associated with intra abdominal thyroid tissue]. AB - A 17-year-old female underwent surgical removal of a painless submental lump presumed to be a median cervical cyst. Histology showed a papillary thyroid carcinoma with invasion of the surrounding connective tissue. A 99m-technetium scan, performed in preparation for a planned total thyroidectomy, demonstrated no thyroid tissue. On subsequent 123-iodine scanning there was an area of increased uptake about 3 cm above the larynx, but no normal thyroid tissue. Histological sections, obtained during further surgical exploration of the base of the tongue, showed scattered thyroid cell rests in the lingual muscles. Whole-body scanning, carried out in connection with administration of radioiodine for ablation of remaining thyroid tissue, disclosed an unexpected area of increased uptake in the epigastrium. Sonography and CT scans failed to demonstrate any corresponding morphological abnormality. Following a further dose of radioiodine 4 months later, no areas of increased uptake were noted. PMID- 1902163 TI - Effect of recombinant inhibin on gonadotropin secretion during proestrus and estrus in the rat. AB - This work investigated the ability of recombinant human (rh) inhibin A or the GnRH antagonist [Ac-D2Nal1, delta Cpa2, delta 3Pal3, Arg5 delta 5-(p methoxyphenyl)5-oxo-2-aminopentanoic acid6, delta Ala10]GnRH to alter plasma immunoreactive LH and FSH levels in cycling female rats. In a first series of experiments, rh inhibin A (25 micrograms/kg) was injected iv between 0800 and 0830 h, or at 0800 and 1200 h, on proestrus, and plasma hormone levels were measured from 1200-1900 h. Both regimens of administration significantly (P less than or equal to 0.01) lowered mean plasma FSH levels but did not mask the primary FSH surge. This treatment also lowered the overall amount of LH released, although the difference between control and inhibin-treated rats only reached statistical significance (P less than or equal to 0.05) after two injections of the protein. Measurement of the number of tubal ova shed on the next estrus showed no difference between rats injected with the vehicle or inhibin at 0830 h. Finally, it was shown that administration of the GnRH antagonist (100 micrograms/kg) at 1200 h interfered with the primary surges of both LH and FSH. In a second series of experiments, rh inhibin A (25 micrograms/kg) was injected once at 2000 h on proestrus. In these animals, inhibin significantly (P less than or equal to 0.01) decreased mean plasma FSH levels between 2000 h on proestrus and 0500 h on estrus and totally suppressed the secondary FSH surge. LH secretion remained low in control animals, and no measurable changes were observed after inhibin treatment. Flushing of the ova 5 days later (i.e. during estrus of the subsequent cycle) showed no difference between control and inhibin-treated rats. Injection of the GnRH antagonist (100 micrograms/kg) at 2000 h on proestrus decreased the total amount of FSH secreted during late proestrus and early estrus. However, FSH secretion showed an increase at between 0100 and 0400 h of estrus despite blockade of GnRH receptors. These results indicate that administration of rh inhibin A interferes with both the primary and secondary FSH surges. In contrast to its inability to alter LH release by ovariectomized rats, inhibin also blunted LH secretion during the afternoon of proestrus. Whether these results represent differential effects of inhibin on LH secreted by intact and gonadectomized animals, or whether the documented changes in pituitary responsiveness to GnRH during proestrus are accompanied by an increased sensitivity to inhibin, needs further investigation. PMID- 1902164 TI - Mammosomatotropes are abundant in bovine pituitaries: influence of gonadal status. AB - Mammosomatotropes--cells that secrete both GH and PRL--are a common pituitary cell type in a variety of mammalian species. Recently, immunogold electron microscopy was used to demonstrate that all acidophils (a generic term used here to denote cells which secrete GH and/or PRL) in cattle stain for both GH and PRL. This high degree of overlap, which is unique among the mammalian species examined in this regard, raises the question: do all acidophils actively release both hormones concurrently? In the present study, we addressed this question by employing reverse hemolytic plaque assays to measure GH and PRL release from individual bovine pituitary cells in culture in the presence of stimulatory secretagogues. Inconsistent with the previous reports on hormone storage, all bovine acidophils in gonad-intact and castrated males did not actively release both GH and PRL. In gonad-intact males approximately 9% of all pituitary cells released both hormones, whereas 21% released only GH and 45% PRL alone. In castrated males, mammosomatotropes comprised only 22% of the pituitary cell population, whereas GH-only cells accounted for 8% and PRL secretors 46%. This divergence in the relative proportions of GH-only cells and mammosomatotropes suggests that the hormonal milieu plays an important role in maintenance of the various acidophilic cell types. In addition, the reciprocal relationship between cells that released GH-only and dual hormone secretors in the two models studied supports the possibility that these cell types are functionally interconvertible. PMID- 1902165 TI - Reduced serum inhibin concentrations during ovulatory cycles of estrogen-treated rhesus monkeys: an indicator of FSH bioactivity. AB - Female rhesus monkeys treated with exogenous estrone initially were anovulatory. Although estrone and estradiol concentrations were maintained 1.5- to 2.5-fold elevated, i.e. in the midfollicular range, ovulatory cycles resumed in three of four animals after 6-15 months of anovulation. During the ovulatory cycles the serum bio LH concentrations were the same in estrone-treated animals as during ovulatory cycles of control monkeys, but the daily basal serum FSH concentrations detectable by RIA were significantly reduced during the ovulatory cycles of the estrone-treated animals compared to the cycles of the controls. In the present study serum inhibin concentrations were measured to determine whether or not they were increased and the cause of the selective decrease in FSH concentrations in the estrogen-treated monkeys. Serum LH, FSH, progesterone, and inhibin concentrations were measured by RIA in blood samples collected during the third year of continuous estrogen treatment. The lack of an effect of elevated estrogen on LH concentrations and a significant estrogen-induced decrease in serum FSH concentrations during ovulatory cycles was confirmed (FSH, control: 5.6 +/- 0.68 ng/ml; estrogen-treated: 2.5 +/- 0.09 ng/ml; P = 0.01). There was also a significant decrease in the serum inhibin concentrations detectable by RIA during the follicular phase of the estrone-treated monkeys compared to the follicular phase of the control animals (119 +/- 17 vs. 462 +/- 105 microliter eq/ml; P = 0.04). These results indicate that the lower serum concentrations of FSH in the estrogen-treated monkeys were not a result of an increase in ovarian secretion of inhibin. The lower inhibin concentrations suggest that FSH bioactivity, as well as immunoreactive FSH, is significantly reduced during the ovulatory cycles of the estrone-treated monkeys. Even though the estrogen treatment decreased the FSH bioactivity, sufficient FSH secretion occurs in the presence of the elevated estrone and estradiol concentrations to induce and support apparently normal ovulatory cycles. PMID- 1902166 TI - Characterization of latent transforming growth factor-beta 2 from monkey kidney cells. AB - Serum-free medium conditioned by BSC-40 cells was analyzed for the presence of transforming growth factor-beta 2 (TGF beta 2)-related proteins. Western blot analysis was performed using site-specific antipeptide antibodies directed against the pro- and mature regions of the TGF beta 2 precursor. When conditioned medium was analyzed by polyacrylamide gel electrophoresis under reducing conditions, proteins with mol wt of 53 kDa (containing both mature and proregion sequences), 34-38 kDa (containing proregion sequences only), and 12 kDa (containing mature sequences) were detected. Under nonreducing conditions, complexes of 60- to 80-kDa, 160- to 200-kDa, as well as 24-kDa mature dimers were seen. Cleavage of mature TGF beta 2 from its precursor was inhibited by monensin and chloroquin, but not by ammonium chloride or methylamine. Two peaks of bioactivity were detected after fractionation on a TSK column corresponding to mol wt of 130 and 400 kDa. These peaks contained TGF beta 2 and pro-TGF beta 2 proteins. Partial purification of the 130-kDa complex followed by N-glyconase digestion indicated that the pro-TGF beta 2 proteins were glycosylated. These data demonstrate that BSC-40 cells secrete mature TGF beta 2 complexed with proregion-containing proteins and suggest that this association may contribute to the latency phenomena observed with respect to this growth regulator. PMID- 1902167 TI - Regulation of luteinizing hormone receptor messenger ribonucleic acid levels by gonadotropins, growth factors, and gonadotropin-releasing hormone in cultured rat granulosa cells. AB - The induction of LH receptors in granulosa cells is prerequisite for ovarian follicles to ovulate and form corpora lutea. Earlier studies have demonstrated the modulatory role of gonadotropins, growth factors, and GnRH on ovarian LH receptor content. We have now analyzed the influences of gonadotropins (FSH, LH, and PRL), several growth factors, and GnRH on LH receptor mRNA levels in cultured granulosa cells. Cells were obtained from immature estrogen-treated rats and cultured in medium containing FSH with or without growth factors or GnRH for 48 h. Some cells were also treated with FSH for 48 h, followed by treatment with FSH, LH, or PRL for another 2 days. Cellular total RNA was extracted, and blot hybridization with 32P-labeled LH receptor cRNA or 28S ribosomal RNA cDNA probes was performed. Treatment of granulosa cells with FSH increased the levels of five species of LH receptor mRNAs in a dose- and time-dependent manner. In FSH-primed cells, LH receptor mRNA levels were maintained by FSH, LH, and PRL. In contrast, treatment of cells with basic fibroblast growth factor or epidermal growth factor suppressed FSH induction of LH receptor mRNA in a dose-dependent manner, whereas treatment with insulin-like growth factor-I had no effect. In addition, GnRH suppressed FSH-stimulated LH receptor mRNA levels in a dose-dependent manner; the effects of GnRH could be counteracted by coincubation with a GnRH antagonist, suggesting mediation by specific GnRH-binding sites. These studies demonstrated that the observed stimulatory effects of gonadotropins (FSH, LH, and PRL) and the inhibitory effects of growth factors (epidermal growth factor and basic fibroblast growth factor) and GnRH on LH receptor content are correlated to their regulation of LH receptor mRNA levels. The granulosa cell culture system should provide a useful model for studying LH receptor gene regulation. PMID- 1902168 TI - Coculture of anterior and posterior pituitary cells: selective stimulation of lactotrophs. AB - There is extensive evidence that the posterior pituitary (PP) participates in the regulation of PRL secretion. We recently reported that a putative PRL-releasing factor is localized, and possibly produced, in the intermediate lobe of the PP. The aim of the present investigation was to determine whether cultured PP cells affect anterior pituitary (AP) function in terms of cell content and cumulative release of PRL. Anterior and posterior pituitaries from adult male rats were dispersed with trypsin and cultured either alone or together for 4 and 8 days in serum-free medium. The concentrations of PRL, GH, and LH in cell extracts and culture media were measured by RIA. Coculturing of AP and PP cells at different plating densities resulted in a 2-fold rise in PRL cell content after 4 days. The cumulative release of PRL in the cocultures was significantly increased only after 8 days. LH and GH were affected slightly, or not at all. Medium conditioned by PP cells mimicked the effects of coculture on the cumulative release of PRL, but not on the cell content. Short-term incubation with TRH induced a much larger release of PRL from AP + PP cocultures than from AP cells cultured alone. In conclusion, these data suggest that 1) PP cells stimulate the production and release of PRL in a hormone-specific manner, and 2) coculturing of AP + PP cells augments the responsiveness of lactotrophs to secretagogues such as TRH. We propose that at least two factors, one of which might be PRL-releasing factor, are involved in these effects. PMID- 1902170 TI - Dopamine inhibits inositol phosphate production, arachidonic acid formation, and corticosteroid release by frog adrenal gland through a pertussis toxin-sensitive G-protein. AB - We have previously shown that dopamine-evoked inhibition of corticosteroid production from adrenocortical cells is mediated through a decrease in prostaglandin biosynthesis. Since the catecholamine did not alter the stimulatory effect of arachidonic acid, it was proposed that dopamine may inhibit the formation of arachidonate from glycerophospholipids. To test this hypothesis, the effect of dopamine on phosphoinositol lipid metabolism was investigated in frog interrenal (adrenal) tissue. In [3H]myo-inositol-prelabeled frog interrenal slices, a short pulse of dopamine (50 microM) induced a biphasic effect on inositol phosphate production: a transient (1-min) increase, followed by a sustained inhibition. Concurrently, dopamine induced a transient reduction followed by a sustained increase in polyphosphoinositides. A 10-min pulse of the D2 dopamine receptor agonist apomorphine (50 microM) elicited a significant inhibition of basal levels of inositol phosphates (tris-, bis-, and mono-), and an increase in plasma membrane phosphoinositol lipid contents. The inhibitory effect of dopamine on inositol phosphate formation and corticosteroid release was abolished by a 24-h incubation of interrenal slices with pertussis toxin. In [3H]arachidonic acid-prelabeled interrenal slices, dopamine also decreased diacylglycerol (DG) and arachidonic acid (AA) concentrations. A delay of 1 min was observed between inhibition of DG and arachidonate, suggesting that AA is probably generated from DG. We conclude that in the adrenal cortex, activation of dopamine D2 receptors is coupled to a phosphoinositide-specific phospholipase-C mediated via a pertussis toxin-sensitive G-protein. Taken together, our data indicate that inhibition of inositol phosphate and AA formation is one of the mechanisms by which dopamine controls corticosteroid production by adrenocortical cells. PMID- 1902169 TI - Mechanism of regulation of prostaglandin production by parathyroid hormone, interleukin-1, and cortisol in cultured mouse parietal bones. AB - Bovine PTH-(1-34) (PTH), human recombinant interleukin-1 alpha (IL-1), and cortisol were tested for their effects on bone resorption, prostaglandin (PG) production, and PG endoperoxide synthase (PGH synthase or cyclooxygenase) mRNA levels in cultured mouse parietal bones. Cultures were treated with PTH and IL-1 in the presence and absence of cortisol and arachidonic acid (AA). We found that both PTH and IL-1 stimulated the release of PGE2 and 6-keto-PGF1 alpha (the stable metabolite of PGI2). Stimulation of each metabolite by IL-1 at 0.6-60 pM was 2- to 118-fold, and that by PTH at 24 pM to 24 nM was 3- to 53-fold. Thus, IL 1 was 40-fold more potent than PTH in stimulating PG release. Moreover, IL-1 showed 2- to 3-fold greater efficacy than PTH in stimulating PGE2 release. However, IL-1 was only 4-fold more potent and no more effective than PTH in stimulating 45Ca release. IL-1 (60 pM) and PTH (2.4 nM) stimulation of PGE2 production showed a similar time course, with a lag phase of 0.75-1.5 h. Cortisol (1-100 nM) reduced basal PGE2 production and calcium release. The absolute amounts of PG produced in response to PTH and IL-1 were reduced in the presence of cortisol, but in the presence of AA the relative increases were still from 2.5 to 26-fold compared with levels in cultures treated with cortisol alone. Cortisol reduced the stimulation of 45Ca release by IL-1, but not by PTH. AA (10( 5) M) amplified PG production in response to PTH and IL-1, but not 45Ca release. In bones labeled with [3H]AA, IL-1 and PTH increased [3H]PGE2 and [3H]6-keto-PGF1 alpha release, as measured by HPLC and TLC. IL-1 slightly increased [3H]AA release, but PTH did not. Cortisol decreased [3H]AA release. To test for an effect on PG production at the level of PGH synthase, mRNA levels were measured. mRNA was increased by both PTH and IL-1 to a similar extent despite the greater effect of IL-1 on PGE2 production. Cortisol did not change PGH synthase mRNA levels and did not block the stimulation by PTH or IL-1. We conclude that IL-1 is a more potent stimulator of PG production and bone resorption than PTH. Stimulation of PG production by both PTH and IL-1 is mediated at least in part by increasing PGH synthase, but IL-1 may have an additional effect on AA release. PMID- 1902171 TI - Exons 1-10 of the rat LH receptor encode a high affinity hormone binding site and exon 11 encodes G-protein modulation and a potential second hormone binding site. AB - We have reported that the rat LH receptor is encoded by 11 exons of a single copy gene. Exons 1-10 encode the N-terminal half and exon 11 the C-terminal half. Since exon splice sites often mark structural transitions of multiexon molecules, we have attempted to define the function of the exons by generating mutant receptors with missing exons. As a first step, we have constructed two LH mutant receptors, one containing exons 1-10 (LH receptor (exon)1-10) and the other containing exon 1 and exon 11 (LH receptor(exon)1&11). These mutant receptors were functionally expressed in Cos 7A cells. The LH mutant receptor(exon)1-10, which lacks the membrane associated C-terminal half of the receptor, showed a high affinity for hCG. Surprisingly, the LH mutant receptor(exon)1&11 recognized hCG with a low affinity and stimulated G-proteins and cAMP production. The results demonstrate that exons 1-10 encode a high affinity hCG binding site and proves an important hypothesis that exon 11 encodes the site for receptor modulation to activate G-proteins. Furthermore, the results raises an intriguing possibility of a second hormone binding site in the C-terminal half and multistep hormone binding. PMID- 1902172 TI - Differential reactivity of V beta 9 T cells to minor lymphocyte stimulating antigen in vitro and in vivo. AB - The monoclonal antibody (mAb) MR10-2 is specific for mouse T cells expressing the V beta 9 chain of T cell antigen receptor. This mAb reacts with 2% of peripheral T cells in a number of different strains of mice, but in mice expressing the minor lymphocyte stimulating (Mls)-1a antigen, V beta 9+ T cells recognized by MR10-2 are deleted. However, we failed to demonstrate the Mls-1 a antigen specific response of naive, non-activated V beta 9 T cells in vitro. On the other hand, T cells activated initially with anti-V beta 9 (MR10-2) mAb in vitro are capable of responding to the Mls-1a antigen. These results demonstrate that Mls 1a reactivity of V beta 9 T cells depends on the activation state of the T cells, suggesting a differential activation requirement between naive, non-activated T cells and previously activated T cells. PMID- 1902174 TI - Characterization of the induction of persistence of major histocompatibility complex class II by hybrids of macrophages from bacillus Calmette Guerin resistant mice. AB - Peritoneal macrophages (M phi) from mice that are resistant to infection by Mycobacterium bovis (strain BCG) (Bcgr) can be induced to express major histocompatibility complex (MHC) class II glycoproteins (I-A) continuously upon treatment with 100 units of recombinant interferon-gamma (rIFN-gamma). In contrast, M phi from mice that are susceptible to BCG (Bcgs) express I-A transiently. Persistent expression of I-A does not require the continued synthesis of the glycoprotein. Thus, treatment with cycloheximide (CHX) reduces I A expression by M phi that express I-A transiently but does not affect the expression of I-A that is persistently expressed. It was not possible, in these studies, to characterize the induction of persistence independent of MHC class II expression because of the 24-48 h required for MHC class II synthesis and cycling to the cell surface. During this time, persistence was also induced. To characterize persistence independent of MHC class II induction we have produced M phi-M phi somatic cell hybrids that express I-A constitutively by fusing cells from a Bcgs M phi cell line with M phi from Bcgr mice. Treatment of some of the hybrids with CHX reduced MHC class II expression. The M phi hybrids required treatment with high doses of rIFN-gamma to induce CHX-resistant I-A expression. The induction of the persistence of I-A, following the addition of rIFN-gamma, required a short burst of protein synthesis as well as the presence of rIFN-gamma for at least 3 h. The addition of actinomycin D simultaneously with rIFN-gamma did not prevent the induction of the persistence of I-A expression by one of the M phi hybrids (F6.4). In contrast, the induction of persistence of I-A expression required a longer period of induction than was observed for hybrid F6.4, which was attributed to the requirement for new RNA and protein synthesis by the A1.8 hybridoma. PMID- 1902173 TI - Immune response to soluble exoantigens of Plasmodium falciparum may contribute to both pathogenesis and protection in clinical malaria: evidence from a longitudinal, prospective study of semi-immune African children. AB - Some soluble exoantigens of Plasmodium have lipopolysaccharide (LPS)-like properties and are believed to contribute to the pathogenesis of acute malaria. We have studied cellular and humoral immune responses to several purified exoantigens of Plasmodium falciparum in a cohort of children and compared these responses with their subsequent susceptibility to malaria infection and clinical disease. We found no evidence that either lymphoproliferative or interferon-gamma (IFN-gamma) responses to these antigens were associated with protective immunity. On the contrary, children whose cells produced IFN-gamma after in vitro activation with one of the soluble antigens (Ag7) were more likely to experience clinical manifestations of malaria infection (fever and malaise) than were children whose cells did not produce IFN-gamma. It is possible that exoantigen induced IFN-gamma may exacerbate the LPS-like effects of these antigens. However, serum antibodies to another antigen (Ag2) were more prevalent in children with asymptomatic infections or low parasitemia than in children with fever and higher parasitemia (confirmed clinical malaria), suggesting that these antibodies may contribute to the development of protective immunity. PMID- 1902175 TI - Lymphokine requirements for the development of specific cytotoxic T cells from single precursors. AB - A high cloning efficiency, filler cell-free culture system was developed for the growth of single murine cytotoxic T lymphocyte precursors (CTLp) and their differentiation into cytotoxic T lymphocytes (CTL). The system used nonspecific stimulation with phorbol ester and calcium ionophore in the presence of recombinant lymphokines. The optimal lymphokine combination was interleukin 2 throughout, together with interferon-gamma during the first 6 days and interleukin 6 during the last 2 days of culture. Under these conditions half of all CD4-CD8+ T cells became CTL clones. The CTL were CD4-CD8+CD3+ TcR alpha/beta+ and were derived from CD4-CD8+Pgp-1- precursors. PMID- 1902176 TI - Elevated production of interferon-gamma and interleukin 4 by mature T cells from autoimmune lpr mice correlates with Pgp-1 (CD44) expression. AB - The cell surface glycoprotein, Pgp-1 (CD44), has been shown to be a marker of murine memory T lymphocytes. When activated, Pgp-1hi memory T cells produce strikingly higher amounts of interferon-gamma (IFN-gamma) than naive Pgp-1lo T cells, yet both subsets make similar levels of interleukin (IL)2. Whereas Pgp-1hi cells represent only 20%-25% of peripheral T cells from most strains, this marker is expressed by the vast majority (greater than 90%) of T cells from autoimmune MRL mice homozygous for the lymphoproliferation (lpr) gene. The massive lymphadenopathy that develops in lpr/lpr mice is composed of both non-mature (CD4 CD8-) T cells as well as a greatly expanded number (up to 300-fold) of mature (CD4+CD8-,CD4-CD8+) T cells. Paralleling the expression of high levels of Pgp-1, we find that compared to normal mouse T cells, the lpr mature T lymphocyte subsets are also very high producers on a per cell basis of IFN-gamma and, for the CD4+ subset, IL 4. Increased concentrations of IFN-gamma and IL 4 produced by large numbers of lpr Pgp-1hi mature T cells could contribute to the autoimmune syndrome in MRL lpr/lpr mice through the effects of these cytokines on augmenting MHC class II expression and production of certain classes of antibodies. PMID- 1902177 TI - Islet-infiltrating T cell clones from non-obese diabetic mice that promote or prevent accelerated onset diabetes. AB - In humans and non-obese diabetic mice (NOD), insulin-dependent diabetes mellitus (IDDM) results from a spontaneous T cell-dependent autoimmune destruction of the insulin-producing pancreatic beta cells. Previous data suggest that a delicate balance between autoaggressive T cells and suppressor-type immune phenomena determine whether expression of autoimmunity is limited to insulitis or progresses to IDDM. To resolve the cellular basis of this intricate network of pathogenic CD4+ and CD8+ T cells and the role of T cells in suppressive immune phenomena. T cell clones were propagated directly from islets of NOD mice at the onset of insulitis. Insofar as insulitis, but not IDDM, is universal in NOD mice, we have screened for the in vivo effects of the islet-infiltrating T cell clones upon expression of IDDM, not insulitis. A CD4+ T cell clone, IS-3S7D, proliferates in response to islet antigen(s) and its transfer into prediabetic NOD mice promotes the rapid onset of IDDM. An interleukin 2 (IL 2)-dependent noncytolytic, V beta 11+ CD8+. T cell clones IS-2.15, prevents an accelerated onset diabetes in two distinct models. The present study, which documents the presence of CD4+ diabetogenic T cell clones and CD8+ T cell clones that dampen autoimmunity, gives tangible evidence that opposing autoimmune processes may determine whether an autoimmune-prone host develops frank disease. PMID- 1902178 TI - The presence of eosinophil-activating mediators in sera from individuals with Schistosoma mansoni infections. AB - IgG antibodies and eosinophils kill schistosomula of Schistosoma mansoni in vitro, and there is now evidence to suggest that the main factor that contributes to the expression of purified IgG effector function is the degree of activation of the donor's eosinophils. This study was designed to identify serum-derived activating factors in sera from individuals infected with S. mansoni. Such activating factors may be responsible for enhancing eosinophil cytotoxicity against schistosomula. Serum-borne mediators were prepared by fractionation of sera from infected individuals by gel filtration high-performance liquid chromatography. The eosinophil-stimulating activity of these mediators was assayed by a new method which depends on the increased expression of the CR3 alpha chain (CD11b) on the surface of activated eosinophils. Sera from infected individuals exhibited different levels of eosinophil activation, and activation appeared to be due to several serum factors, including interleukin 5. In conclusion, our results suggest that eosinophil-activating factors present in infection sera may not only be responsible for enhancing eosinophil cytotoxicity but also be necessary for its expression. PMID- 1902179 TI - V lambda-J lambda rearrangements are restricted within a V-J-C recombination unit in the mouse. AB - The murine lambda gene locus is organized as follows: V lambda 2-V lambda x-J lambda 2C lambda 2-psi J lambda 4C lambda 4-V lambda 1-J lambda 3C lambda 3-J lambda 1C lambda 1 where all segments have the same transcriptional orientation. The combinatorial process of gene recombination should allow the generation of eight distinct immunoglobulin light chains. We have therefore investigated the probability of obtaining such chains among the mature lambda B cell repertoire. We analyze serum lambda immunoglobulins and lambda B cell clones induced by treatment with rabbit anti-lambda antibodies coupled to LPS. Confirming previous data obtained by others, our results indicate that the rearrangements of lambda segments take place within each V lambda-J lambda-C lambda cluster, thereby defining a unit of recombination. Our results also provide no evidence for the use of undescribed segments as has been recently suggested by the finding of the V lambda x segment. PMID- 1902181 TI - Presence of CD4 and CD8 determinants on CD4-CD8- murine thymocytes: passive acquisition of CD8 accessory molecules. AB - In the present study we have examined the possibility that CD4 and CD8 accessory molecules can be passively acquired by thymocytes. We initially observed that most thymocytes contained within the CD4-CD8- subset actually possess low levels of CD4 and CD8 on their cell surface. However, the detection of CD4 and CD8 on CD4-CD8- cells was dependent on the presence of other CD4+/CD8+ thymocytes which were actively synthesizing CD4 and CD8. These initial findings suggested that the appearance of CD4/CD8 on "double-negative" thymocytes was due to the passive acquisition of these accessory molecules from CD4+/CD8+ cells present within the thymus. To investigate this possibility directly, we made both in vivo and in vitro mixes of thymocytes possessing different alleles of CD8 (Ly-2.1 and Ly 2.2). Under these experimental conditions, we detected Ly-2.2 on the surface of thymocytes that were genetically Ly-2.1+ and incapable of synthesizing Ly-2.2. These data indicate that thymocytes can express cell surface CD8 molecules which they have not produced but have acquired from other cells in their environment. Thus, the present study indicates that low-level surface expression of cell surface CD4/CD8 differentiation molecules does not necessarily identify distinct thymocyte subpopulations. PMID- 1902180 TI - Correlation between the occurrence of lupus nephritis, anti-erythrocyte autoantibodies and V kappa haplotype in NZB x 129/J and NZB x SM/J recombinant inbred murine strains. AB - The NZB mouse is genetically predisposed to the development of autoimmune disease that resembles the human autoimmune systemic lupus erythematosus and autoimmune hemolytic anemia, with increased titers of anti-DNA, and Coombs' autoantibodies. The various autoimmune traits are controlled separately by a limited number of genes. Genetic studies have shown that several immune loci are involved in autoimmunity: T cell abnormalities, H-2 complex and immunoglobulin genes have been implicated. In this report, we present evidence for a significant correlation of NZB V kappa 1 haplotype defined by restriction fragment length polymorphism analysis with anti-erythrocyte autoantibodies in NZB x 129/J and NZB x SM/J recombinant inbred lines. PMID- 1902182 TI - Effect of penicillin and chloramphenicol on the growth and endotoxin release by N. meningitidis. AB - The action of two antibiotics, penicillin and chloramphenicol, on bacterial growth and endotoxin liberation was studied in 18 strains of Neissevia meningitidis isolated from blood and CSF of patients with meningococcal infections. The antibiotics were administered both separately and in combined form in doses equivalent to 1 MIC and 100 MIC. Penicillin was found to produce a faster and more intense bactericidal effect than chloramphenicol during the first hour, whereas at 12 h these differences were not significant. This could explain the initial worsening observed in some infected patients when large doses of penicillin are administered. An increased liberation of endotoxin after adding penicillin was observed in six of the strains studied, whereas the remaining 12 did not show significant increases. The six strains (belonging to serogroup B) were known to have an enhanced capacity for spontaneous endotoxin liberation. PMID- 1902183 TI - Endotoxin liberation by strains of N. meningitidis isolated from patients and healthy carriers. AB - The main objective of this study was to assess whether the capacity of Neisseria meningitidis to release endotoxin depends upon the type of strain or upon bacterial mass. Endotoxin release was studied in 32 strains isolated from patients with meningococcal infections and in 49 from asymptomatic carriers, using a quantitative test (limulus test with a chromogenic substrate). The results show that the strains from patients release significantly higher amounts of endotoxin than strains from carriers regardless of serogroup and isolation site. No correlation was found between stage of bacterial growth and the amount of endotoxin liberated. These findings suggest that endotoxin liberation is a characteristic of certain strains of N. meningitidis and is not determined simply by bacterial mass. PMID- 1902184 TI - Further observations on enhancement of the infectivity of Fusobacterium necrophorum by other bacteria. AB - It had already been shown with a single virulent strain (A42) of Fusobacterium necrophorum that suspension of the fusobacteria in sub-lethal doses of broth cultures of other bacteria reduced the minimum infective dose (greater than 10(6) organisms) for mice by subcutaneous inoculation, sometimes to less than 10 organisms. The present study extended the known range of bacteria with strong infectivity-enhancing properties to include Bacillus cereus, Klebsiella oxytoca and Staphylococcus aureus; and those with weaker effect to include Bacillus subtilis, 'Bacteroides melaninogenicus', Clostridium sporogenes, Pasteurella haemolytica, and Proteus mirabilis. The study also showed that five further virulent strains of F. necrophorum closely resembled A42 in respect of striking susceptibility to infectivity enhancement by Escherichia coli. Actinomyces (Corynebacterium) pyogenes and S. aureus. One further strain (A6) of F. necrophorum resembled A42 in respect of strong infectivity enhancement by A. pyogenes, S. aureus, B. cereus and K. oxytoca but differed from it and the other five strains in being only slightly affected by E. coli. This work was a necessary prelude to the development of a method, based on infectivity enhancement, for the detection and isolation of F. necrophorum present in small numbers in heavily contaminated material such as faeces. PMID- 1902185 TI - Antibodies in horses, mules and donkeys following monovalent vaccination against African horse sickness. AB - A total of 256 sera collected from three species of domesticated equidae in four different Spanish provinces were examined 1-4 months after the administration of attenuated monovalent African horse sickness virus (AHSV) serotype 4 vaccine. Approximately 10% of the sera were negative by ELISA, virus neutralization, agar gel immuno-diffusion and complement fixation tests. Similar negative reactions were recorded with sera from two ponies after experimental primary vaccination. The rapid rise in antibodies in sera from these two ponies, after a second dose of vaccine, suggested they would probably have been immune to challenge. It is therefore suggested that the apparent absence of antibodies against AHSV in some animals after primary vaccination may not necessarily indicate a total lack of protection. PMID- 1902186 TI - Viraemic transmission of Crimean-Congo haemorrhagic fever virus to ticks. AB - In order to determine the way in which vertebrates infected with Crimean-Congo haemorrhagic fever (CCHF) virus and potential ixodid tick vectors interact in nature, immature and adult ticks of several species were fed on viraemic mammals and then assayed for virus content at varying times after feeding. CCHF virus was not isolated from ticks of six species tested after feeding as adults and immature forms on sheep with viraemia of 10(2.5-3.2) LD 50/ml, nor from larval ticks fed on guinea-pigs and white-tailed rats with viraemia of 10(1.9-2.7) LD 50/ml. In contrast, virus was isolated from 10 of 152 pools of engorged adult ticks of 5 species that fed on cattle with viraemia of 10(1.5-2.7) LD 50/ml and from 3 of 137 female ticks after oviposition. Infection was transmitted to larval and nymphal Hyalomma truncatum and H. marginatum rufipes, but not to Rhipicephalus evertsi evertsi, from a scrub hare with viraemia of 10(4.2) LD 50/ml but only nymphal H. truncatum and H. m. rufipes became infected from scrub hares with viraemia of 10(2.6-2.7) LD 50/ml. Infection was transmitted trans stadially in H. m. rufipes and H. truncatum infected as nymphae, and adult H. m. rufipes transmitted infection to a sheep. No evidence of transovarial transmission was found in larval progeny of ticks exposed to CCHF virus as adults on sheep and cattle or as immatures on scrub hares. PMID- 1902187 TI - Changes in temporal and spatial patterns of Gi protein expression in postimplantation mouse embryos. AB - We previously demonstrated the presence of GTP-binding proteins, G proteins, in the preimplantation mouse embryo (Jones and Schultz, 1990. Dev. Biol. 139, 250 262). These studies have been extended to the Day 6.5, 7.5, and 8.5 gestation embryo by employing PT-catalyzed ADP-ribosylation and immunoblotting techniques. We report here that the amount of embryonic alpha i increases from Day 6.5 to Day 7.5 of gestation, and remains at about the same level at Day 8.5. In contrast, the extent of PT-catalyzed ADP-ribosylation of Gi alpha protein(s) decreases between Days 6.5 and 7.5--this decrease is global and not restricted to a particular germ layer of the Day 7.5 embryo--and then dramatically increases by Day 8.5 of gestation. In the Day 8.5 gestation embryo, the extent of PT-catalyzed ADP-ribosylation of Gi alpha proteins increases along the anterior-posterior axis, whereas the amount of immunoreactive alpha i subunit decreases along this axis. By using a combination of PT-catalyzed ADP-ribosylation and immunoprecipitation with antisera specific for alpha i1, alpha i2, or alpha i3, we report that all three alpha i subtypes are present in the Day 8.5 gestation mouse embryo. Results of these experiments suggest that an activation of Gi proteins occurs between Days 6.5 and 7.5 of gestation in the postimplantation embryo, a time during which the embryo is gastrulating, and that a decreasing gradient of activation exists along the anterior to posterior axis in the Day 8.5 gestation embryo. Last, we report that oocytes, eggs, and preimplantation embryos possess all three subtypes of alpha i. PMID- 1902188 TI - Acute testicular toxicity of 1,3-dinitrobenzene and ethylene glycol monomethyl ether in the rat: evaluation of biochemical effect markers and hormonal responses. AB - The studies described in this paper were undertaken to evaluate the use of plasma enzymes of testicular origin and plasma hormones as markers of acute testicular toxicity. Rats were dosed by gavage with a single dose of either 1,3 dinitrobenzene (1,3-DNB) or ethylene glycol monomethyl ether (EGME). Two experimental designs were used: a dose response and a time-dose response course. Lactate dehydrogenase isozyme C4 (LDH-C4) and sorbitol dehydrogenase (SDH) were used as germ cell markers and leucine aminotransferase (LAT) and androgen binding protein (ABP) were used as Sertoli cell markers. Luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone were also monitored. Histopathology confirmed the known testicular toxicity of 1,3-DNB and EGME. 1,3 DNB induced Sertoli cell damage with associated degenerative changes in late pachytene spermatocytes. The effects of EGME were mainly on early and late pachytene and dividing spermatocytes. No changes in either testicular or plasma SDH or LAT were found. Similarly no effects were observed for plasma LH or testosterone. However testicular LDH-C4 and testosterone, plasma LDH-C4, ABP, and FSH did show compound related effects. LDH-C4 was reduced in testis and increased in plasma with both compounds and plasma LDH-C4 remained elevated up to 14 days after dosing. ABP levels in plasma were increased with 1,3-DNB and EGME. A reduction in testicular testosterone levels was recorded and plasma FSH concentrations were elevated after EGME treatment. It is concluded that plasma LDH-C4 activity and ABP may be of diagnostic value in acute testicular toxicity. Increases in plasma LDH-C4 precede noticeable histological findings. PMID- 1902189 TI - The influence of zinc status and malnutrition on immunological function in Crohn's disease. AB - Cellular immunity is likely to be important in the pathogenesis of Crohn's disease; whether it is abnormal is not clear. The heterogeneity of patients with Crohn's disease probably underlies the disparity of reports, but attempts to determine which clinical features influence cellular immunity have been largely unsuccessful. This is probably caused by the omission of nutritional status as a potential factor, even though zinc deficiency has frequently been linked with abnormal immunity. Therefore, a detailed study of nutritional and tissue zinc status, nonspecific cellular immunity, and a measure of phagocytic function was performed in 32 patients with Crohn's disease and in a control group of 18 normal subjects and 12 patients with anorexia nervosa. Fourteen patients with Crohn's disease, all patients with anorexia nervosa, but none of the normal controls were malnourished. Peripheral blood lymphocyte population levels were normal in patients with Crohn's disease and in normal controls, but there was a small decrease in the levels of patients with anorexia nervosa. In vivo delayed hypersensitivity skin test responses were profoundly depressed in patients with anorexia nervosa and decreased in patients with Crohn's disease who were malnourished or receiving systemic glucocorticoids. In vitro lymphocyte transformation was reduced in malnourished patients with Crohn's disease, but there were only minor changes in patients with anorexia nervosa. There were alterations of in vitro immunoregulation in Crohn's disease, but they were not responsible for the abnormal lymphocyte transformation responses in malnourished patients. In vitro phagocytic function was reduced in patients with active Crohn's disease. These findings suggest that depressed in vivo and in vitro cellular immunity in malnourished patients with Crohn's disease is caused by a qualitative lymphocyte defect and that depressed in vivo but normal in vitro cellular immunity in anorexia nervosa is caused by a quantitative defect. Thus, malnutrition in Crohn's disease resembles kwashiorkor; in anorexia nervosa, it resembles marasmus. Tissue zinc status was mostly normal in Crohn's disease and anorexia nervosa, and zinc deficiency was not responsible for depressed nonspecific cellular immunity in either condition. PMID- 1902190 TI - Signs of cellular immunosuppression correlate with HLA-DR phenotypes in healthy HIV-negative homosexuals: preliminary findings. AB - Twelve healthy, anal-receptive, homosexual Caucasian males who were seronegative for HIV antibody were typed for HLA-DR antigens. Flow cytometry was used to immunophenotype peripheral blood lymphocytes bearing the CD4, CD8, LEU7, and combined CD8 and LEU7 antigens. These individuals had reported a large number of sexual partners within a five-year period preceding this study. Each individual was assigned a score based on the Hardy-Weinberg frequency of their HLA-DR phenotype in the Caucasian population. The larger the value of this score, the more common the HLA-DR phenotype, the smaller the score, the rarer the phenotype in the population at large. A significant inverse correlation was observed between this score and the proportion of lymphocytes with CD8 and LEU7 antigens. Lymphocytes bearing these two antigens have in vitro suppressor activity and are elevated in patients with human immunodeficiency virus (HIV) infection. The inverse association between CD8+/LEU7+ cells and frequency of HLA-DR phenotypes is consistent with the hypothesis that individuals with rarer phenotypes whose partners are drawn from the population at large are more likely to be challenged during anal insemination, which results in immunosuppression (alloantigenic challenge hypothesis). On the other hand, it is possible that an association exists between certain HLA-DR phenotypes and immune status. Although these observations were made in a very small sample, we believe that the strength of this association provides justification for further investigation into the possibility that alloantigenic challenge may increase the risk for infection, if exposed to HIV, and augment the immunosuppressive action of HIV once significant infection has occurred. PMID- 1902191 TI - Structure of extrachromosomal circular DNAs generated by immunoglobulin light chain gene rearrangements. AB - Recombination at the immunoglobulin kappa or lambda light chain locus generates extrachromosomal circular DNAs. We have isolated circular DNAs from adult mouse spleen cells and prepared a circular DNA clone library. We characterized four J kappa-positive and one J lambda 1-positive clones. The J kappa-clones contained both coding and signal joints of V kappa-J kappa joining, and the J lambda 1 clone contained a signal joint of V lambda 1-J lambda 1 joining. Genomic organization of the V kappa gene families used in these joints suggested the excision of circular DNA preceded by inversion. A specific dinucleotide (P) insertion in the coding joint was observed in two clones. Three coding joints were out of frame and one clone had an in-frame coding joint, although possibly combined with a pseudo-V kappa gene. These kappa-positive circular DNAs are possibly excised from the chromosome by secondary recombinations which replace non-productive primary rearrangements. PMID- 1902192 TI - Effect of two feeding formulas on immune responses and mortality in mice challenged with Listeria monocytogenes. AB - Cell-mediated immunity and natural killer cells play an important role against facultative intracellular organisms. The effect of two commercially available tube feeding formulas used for patients with acute or chronic debilitating and life-threatening illnesses was studied in mice challenged with Listeria monocytogenes. C57BL/6 X DBA/2 F1 hybrid mice were given ad libitum access to one of two formulas or to chow. Sixty mice in each of the feeding groups were challenged with 4.8 X 10(3) organisms intraperitoneally. Mortality was significantly less in animals fed Impact, a formula enriched with arginine, RNA and selected fatty acids. This was associated with reduced number of viable organisms in the spleen on day 7 after challenge. There was no difference in the spleen/body weight index between the different groups. Delayed cutaneous hypersensitivity was slightly higher in the Impact group but this was not statistically significant. Natural killer cell activity was significantly higher in the Impact group compared with the other two feeding regimens. These observations suggest that selective manipulation of the composition of tube feeding formulas may have a significant impact on immune responses and on morbidity and mortality following infectious challenge. PMID- 1902193 TI - Gamma interferon suppresses acute and chronic Trypanosoma cruzi infection in cyclosporin-treated mice. AB - To determine if exogenous gamma interferon is effective in immunosuppressed mice infected with Trypanosoma cruzi, recombinant murine gamma interferon was administered to cyclosporin-treated mice with either acute or chronic T. cruzi infection. Gamma interferon significantly decreased parasitemia and prevented death in acutely infected mice. Parasitemias and mortality of mice treated with both gamma interferon and cyclosporin were similar to those of immunocompetent controls. In chronically infected mice, cyclosporin treatment produced significantly more organ explant cultures positive for T. cruzi. Fewer positive cultures, particularly for spleen and heart, were obtained from cyclosporin treated mice when they also received gamma interferon. Ketoconazole treatment of mice resulted in no positive cultures. Cyclosporin treatment did not prevent activation of peritoneal macrophages by parenteral gamma interferon, nor did it have a consistent effect on serum titers of alpha/beta or gamma interferon in response to a second challenge inoculum of T. cruzi. These data indicate that exogenous gamma interferon suppresses acute and chronic T. cruzi infection in cyclosporin-treated mice but that gamma interferon is not as effective as the relatively specific antimicrobial ketoconazole. Gamma interferon activates macrophages despite cyclosporin treatment, and its effects appear to be tissue specific. PMID- 1902194 TI - In vivo protective effect of lipopolysaccharide against Pseudomonas aeruginosa exotoxin A in mice. AB - Lipopolysaccharide (LPS) treatment of mice 1 to 5 days prior to administration of Pseudomonas aeruginosa exotoxin A (PA) induced full or partial protection against PA intoxication. The optimal LPS dose that induced resistance was 50 to 100 micrograms per mouse. Simultaneous administration of LPS and PA to mice, however, increased their sensitivity to PA two- to fourfold. Mice pretreated with LPS demonstrated a markedly enhanced clearance rate of 125I-labeled PA from peripheral blood, livers, and kidneys. In mice exposed to LPS and PA simultaneously, the rate of elimination of labeled PA was lower than that in control mice. While protein synthesis was inhibited significantly in livers and other organs of PA-exposed mice, in LPS-pretreated mice, PA-induced inhibition of protein synthesis was either diminished or totally prevented and elongation factor 2 (EF2) levels were normal. In mice treated only with LPS, enhanced protein synthesis and increased levels of EF2 were observed, suggesting that LPS protection against PA intoxication was perhaps a consequence of excessive amounts of EF2 induced by LPS. PMID- 1902196 TI - Characterization of the components of hemolysin BL from Bacillus cereus. AB - Previously we described the partial purification of a novel hemolysin from Bacillus cereus and showed that hemolytic activity required the combined action of at least two components, called B and L to signify their cell-binding and cell lytic roles in this activity. On further purification, as described in the present article, a combination of anion-exchange chromatography and polyacrylamide gel electrophoresis separated three proteins, B, L1, and L2 (35, 36, and 45 kDa, respectively). Individually, these proteins were inactive in hemolytic and vascular permeability assays, and combinations of B and L1 or B and L2 were either inactive or slightly active. Combinations of all three moieties produced the unique ring-shaped zone of hemolysis, a previously described characteristic of hemolysin BL, as well as edema and bluing in the vascular permeability assay. Since the vascular permeability assay is known to correlate with enterotoxicity, these results suggest that hemolysin BL is enterotoxigenic. Furthermore, the molecular weights and isoelectric point values of the hemolysin BL components are consistent with those described by others for the multicomponent diarrheal enterotoxin of B. cereus. Immunofluorescent staining of B-treated erythrocytes confirmed that B binds to cells as an initial step required before the L components can act to cause cell lysis. PMID- 1902195 TI - Regulation of gamma interferon production by natural killer cells in scid mice: roles of tumor necrosis factor and bacterial stimuli. AB - CB-17 scid mice exhibit a T-cell-independent but gamma interferon (IFN-gamma) dependent immunity to Listeria monocytogenes. In this study, we analyzed the specific cellular interactions involved in this process. scid mouse-derived natural killer (NK) cells cultured with heat-killed (HK) L. monocytogenes and macrophages secreted IFN-gamma. No IFN-gamma was produced in cultures containing HK L. monocytogenes but lacking macrophages. However, medium derived from macrophages incubated with HK L. monocytogenes or other microorganisms stimulated IFN-gamma production by isolated NK cells. Treatment of macrophage-conditioned supernatants with neutralizing monoclonal anti-tumor necrosis factor (TNF) significantly reduced their capacity to stimulate NK cells to produce IFN-gamma. Yet, purified recombinant TNF-alpha by itself was unable to stimulate NK cells. Thus, TNF was necessary but not sufficient to induce maximal IFN-gamma production by NK cells. Sonicated L. monocytogenes stimulated production of IFN-gamma by NK cells that was resistant to anti-TNF. Stimulation was markedly enhanced by the addition of recombinant TNF-alpha. These studies demonstrated that activation of scid NK cells for secretion of IFN-gamma requires two signals: TNF-alpha and a second product which may be of bacterial origin and may require processing by mononuclear phagocytes. We suggest that the T-cell-independent production of IFN gamma by NK cells provides the host with a rapid mechanism to temporarily heighten nonspecific resistance to infection until such time as T-cell-dependent sterilizing immune responses can be generated. PMID- 1902197 TI - Synthetic peptide substrates for the immunoglobulin A1 protease from Neisseria gonorrhoeae (type 2). AB - Neisseria gonorrhoeae secretes protease which inactive human immunoglobulin A1 (IgA1) by cleavage of specific peptide bonds in the hinge region. The type 2 IgA1 protease (EC 3.4.24.13) is secreted as a 169-kDa precursor which undergoes autoproteolysis at three sites (A, B, and C) to release the 106-kDa active form of the enzyme (J. Pohlner, R. Halter, K. Beyreuther, and T. F. Meyer. Nature [London] 325:458-462, 1987). Synthetic decapeptides consisting of five residues on each side of the three autoproteolytic cleavage sites and their potential pentapeptide catabolites were prepared by solid-phase synthesis. Cleavage of the decapeptides by the type 2 IgA1 protease from N. gonorrhoeae was monitored by high-performance liquid chromatography. Peptides homologous with the amino acid sequences around the B and C sites are cleaved by the IgA1 protease. Amino acid analysis and Edman degradation show that the cleavage products have both the composition and amino acid sequence which would be expected from cleavage at the predicted sites. Km values of 1.35 mM and 3.43 mM and kcat values of 280 pmol/h/U and 439 pmol/h/U for the site B and site C peptides, respectively, were determined. The catalytic efficiency (kcat/Km) for the synthetic substrates is about 10% of that reported for intact IgA1. Cleavage of the peptides is inhibited by IgA1 protease inhibitors such as the tetrapeptide substrate analog inhibitor HRP-48, human colostrum, and a peptide-boronate transition state inhibitor. An extract from an N. gonorrhoeae construct lacking active IgA1 protease failed to cleave the synthetic substrate, while an extract from the control construct which secretes active enzyme completely hydrolyzed the synthetic peptide. Neither the site A peptide nor synthetic decapeptides encompassing cleavage sites in the hinge region of IgA1 are hydrolyzed by IgA1 protease. These are the first synthetic substrates to be reported for any IgA1 protease. PMID- 1902198 TI - Evidence that vesicles containing living, virulent Mycobacterium tuberculosis or Mycobacterium avium in cultured human macrophages are not acidic. AB - Mycobacterium tuberculosis and Mycobacterium avium multiply in cultured human macrophages (MP) within membrane-enclosed vesicles. These vesicles are generally assumed to be acidic. The evidence most frequently cited for this assumption is that pyrazinamide, which requires an acid pH to be effective, is effective and streptomycin, which loses most of its activity at a low pH, is poorly effective against tubercle bacilli. This assumption was tested by using the two weak bases chloroquine and NH4Cl to raise the pH of acidic vesicles in MP experimentally infected with M. tuberculosis or M. avium. An immunocytochemical locator of acidic regions in the MP was used to monitor the association of intracellular bacilli with acidity. MP were infected with M. tuberculosis or M. avium and incubated with various combinations of the drugs and the weak bases. Replication of the bacteria in the MP was measured by culture counts. Intracellular associations of the mycobacteria with acidity were assessed by electron micrographs and by using the weak base 3-(2,4-dinitroanilino)-3'-amino-N-methyl dipropylamine, which was detected with colloidal gold-labeled antibodies. It was confirmed by immunocytochemistry that both chloroquine and NH4Cl raise the pH of acidic vesicles in the infected MP. However, neither caused any pH-related change in the antimycobacterial activities of pyrazinamide or streptomycin or of the pH independent drug isoniazid. Immunochemical analyses showed acidity to be associated with killed but not living mycobacteria in the MP. These findings suggest that living M. tuberculosis and M. avium are located in human MP in vesicles which are not acidic. PMID- 1902199 TI - Hemolytic and sphingomyelinase activities of Clostridium perfringens alpha-toxin are dependent on a domain homologous to that of an enzyme from the human arachidonic acid pathway. AB - The N-terminal domain of Clostridium perfringens alpha-toxin, homologous with the nontoxic phospholipase C of Bacillus cereus, was expressed in Escherichia coli and shown to retain all of the phosphatidylcholine hydrolyzing activity of the alpha-toxin, but not the sphingomyelinase, hemolytic, or lethal activities. The C terminal domain of alpha-toxin showed sequence and predicted structural homologies with the N-terminal region of arachidonate 5-lipoxygenase, an enzyme from the human arachidonic acid pathway which plays a role in inflammatory and cardiovascular diseases in humans. PMID- 1902201 TI - Plasminogen activators in human gastric cancers: correlation with DNA ploidy and immunohistochemical staining. AB - Plasminogen activator activity was investigated in extracts of 42 surgically removed gastric carcinomas. The mean levels of total plasminogen activator (total PA) and urokinase-type plasminogen activator (u-PA) activities in the gastric carcinomas were significantly higher than those in the background normal tissues (p less than 0.001). On electrophoresis, gastric cancers were found to contain u PA as the predominant PA, this being confirmed using zymography by direct inhibition with anti-urokinase antibody. Assessment of the relationship between PA activity and biological behavior of gastric cancer revealed total-PA and u-PA levels to be significantly higher in differentiated than in undifferentiated tumors (p less than 0.001), and in aneuploid than in diploid ones (p less than 0.01). Immunohistochemical staining showed that the proportion of u-PA-positive cancer cells in the carcinoma tissues also correlated with activity as measured by the azocaseinolytic method. These findings suggest that the study of PA contents in gastric cancer, combined with a nuclear DNA ploidy and immunohistochemical analysis, might be useful for understanding the biological characteristics of the tumor. PMID- 1902200 TI - Non-MHC-restricted target-cell lysis by a CD4-CD8- TCR alpha beta T-cell line, as well as by TCR gamma delta T-cell lines, results from lymphokine-activated killing. AB - A long-term CD4-CD8- TCR alpha beta human T-cell line, as well as similar CD4-CD8 TCR gamma delta T-cell lines for comparison, were generated from various tissues by negative selection using anti-CD4 and anti-CD8 monoclonal antibodies (MAbs) followed by positive selection with specific anti-TCR MAb and then repeated in vitro stimulation with interleukin-enriched media and lectin. These cell lines all demonstrated non-MHC-restricted cytolysis on a variety of human tumor cell lines. However, removal of lymphokines from the culture media for 24 hr abrogated most of the non-MHC-restricted target-cell lysis without affecting TCR alpha beta or TCR gamma delta cell viability or TCR function as determined by antibody triggered redirected target-cell lysis. Subsequent re-exposure to lymphokines reconstituted non-MHC-restricted cytolysis by these cell lines. Thus, much of the non-specific, non-MHC-restricted cytolytic activity generated by CD4-CD8- TCR alpha beta or TCR gamma delta cells is secondary to lymphokine-activated killing (LAK) activity. These cells have potent LAK activity and may be prominent in LAK cell populations. In addition, after lymphokine deprivation, both CD4-CD8- TCR alpha beta and TCR gamma delta cells showed residual activity against some tumor cell targets, the nature of which remains to be defined. PMID- 1902203 TI - Large-scale swine production: a veterinarian's role in a company's bottom line. PMID- 1902202 TI - Immunological and non-immunological influence of H-2Kb gene transfection on the metastatic ability of B16 melanoma cells. AB - The H-2b-negative B78HI clone (derived from B16 melanoma) was transfected with the H-2Kb gene; 4 cell clones expressing membrane H-2Kb antigens and 2 control clones (transfected with pSV2neo alone) were used for studies of metastatic ability, immunogenicity, NK sensitivity and homotypic adhesion. The experimental metastatic capacity of H-2Kb transfectants in syngenic mice was greatly diminished in comparison with control and parent cells. Both immune-mediated and intrinsic properties of transfectants correlated with their lower metastatic ability. A cell-mediated cytotoxic response was induced by repeated in vivo immunizations of syngeneic mice followed by in vitro restimulation of effectors when transfectants (but not controls) were used as immunizers and as targets. Moreover, homotypic adhesion of H-2Kb transfectants was significantly lower than that of controls. Sensitivity to NK cells of transfectants was not decreased in comparison to H-2-negative controls. It is known that in vitro treatment with IFN gamma of H-2-positive B16 melanoma cells induces a simultaneous increase in H-2 expression and in experimental metastasis; treatment of H-2Kb transfectants with IFN-gamma induced a higher Kb expression, but no increase in metastatic ability, thus suggesting that the IFN-sensitive component that mediates enhancement of metastasis is not H-2Kb. PMID- 1902204 TI - Use of the polymerase chain reaction for direct detection of Listeria monocytogenes in soft cheese. AB - The polymerase chain reaction (PCR) amplification technique was investigated as a tool for direct detection of Listeria monocytogenes in soft cheeses. Different sets of oligonucleotide primers were used, and parts of the L. monocytogenes Dth 18-gene could be amplified specifically when either a plasmid vector carrying the cloned gene or chromosomal DNA was used a template. The detection limit for L. monocytogenes in dilutions of pure cultures was between 1 and 10 colony-forming units. In extracts from soft cheeses containing L. monocytogenes DNA, the amplification was strongly inhibited. This inhibition could be reduced by an additional purification step. Despite this the detection limit showed a large variation, depending on the brand of cheese used. In some cheeses 10(3) cfu/0.5g could be visualized whereas in others the presence of 10(8) cfu/0.5 g did not yield a detectable quantity of amplified product. PMID- 1902205 TI - Short-chain organic acids at ph 5.0 kill Escherichia coli and Salmonella spp. without causing membrane perturbation. AB - When strains of Escherichia coli K12 and Salmonella spp. were incubated with 0.5 0.7 mol/l formic or propionic acid at pH 5.0, propionic acid was more active than formic acid. It killed 90% of the cell population within 60 min compared with over 3 h for formic acid. Cell death was not associated with a reduction in culture turbidity or a loss of membrane integrity since morphologically normal membranes were observed by electron microscopy and only a small proportion of the cytoplasmic enzyme beta-galactosidase leaked into the supernatant fluid of acid treated E. coli K12 cultures. PMID- 1902206 TI - Yolk polypeptide gene expression in cultured Drosophila cells. AB - The transfer of chimaeric plasmids to Drosophila melanogaster cell lines has been examined as a system for investigation of the hormonal regulation of the genes coding for D. melanogaster yolk polypeptide 1 (YP1) and Locusta migratoria vitellogenin B (VgB). Constructs containing promoters and putative 5'-regulatory sequences from these genes, ligated to bacterial chloramphenicol acetyltransferase (CAT) coding DNA, were transfected into Drosophila Kc (Kc-H) and S3 cells, and transient expression of CAT was assayed. Activity was expressed both from the homologous promoter of pYP1CAT and from the heterologous locust promoter of pVgCAT at comparable levels. In S3 cells, with calcium phosphate mediated transfer of pYP1CAT there was a twofold induction of CAT activity after the addition of 10(-6) M ecdysterone, but no hormonal stimulation was noted when the polycation polybrene was used to achieve transfection. For Kc cells, calcium phosphate was ineffective for transfection, and after transfection with polybrene neither pYP1CAT nor pVgCAT was induced by the juvenile hormone (JH) analog methoprene. It is concluded that S3 cells may be useful for investigating the molecular basis of gene regulation by ecdysteroids, but conditions suitable for the analysis of JH action have not yet been established. PMID- 1902207 TI - Retinol-induced modification of the extracellular matrix of endothelial cells: its role in growth control. AB - The growth of the endothelial cell (EC) is tightly regulated throughout the body. Many factors have been implicated in modulating EC growth including diffusible compounds, cell-to-cell interactions, and the extracellular matrix (ECM). Retinol, or vitamin A alcohol, has recently been shown to inhibit the growth of bovine capillary ECs, in vitro. Retinoids are known to modify ECM in other cell systems, and pure ECM components have been shown to effect EC growth rates. We, therefore, examined the role of the matrix in the retinol-induced inhibition of ECs. Cell-free matrices from control and vitamin A-treated ECs were prepared by removing cells with EGTA treatment after 7 d of culture. Matrix proteins were analyzed by solubilizing the matrices in 5 M guanidine-HCl and performing Western blot analysis using specific antibodies to matrix proteins. In isolating the ECM, we observed that retinol-treated cultures of ECs were resistant to EGTA removal; retinol-treated ECs required twice the exposure time to EGTA to detach from their matrix than did controls cells. Western blot analysis of matrix proteins derived from control and retinol-treated EC cultures demonstrated a 1.6-fold increase in laminin beta chains and a 2.5-fold increase in fibronectin in the ECM of retinol treated EC compared to control cell matrix. Functional properties of these matrices were assessed by plating control and Day 6 retinol-treated ECs onto the matrices and measuring attachment and growth by determining cell numbers at 24, 72, and 144 h. These studies revealed that control cells attached in greatest numbers to a control matrix whereas retinol-treated ECs preferentially attached to a matrix derived from retinol-treated cells. Furthermore, control ECs which grew rapidly on a control matrix were growth inhibited on a retinol-derived matrix. These data indicate that vitamin A treatment of ECs effects both their phenotype and influences the composition and the functional properties of their underlying ECM. These studies also demonstrate that alterations of the matrix are at least in part responsible for the growth inhibition of EC by retinol. PMID- 1902208 TI - Light-activated heterotrophic growth of the cyanobacterium Synechocystis sp. strain PCC 6803: a blue-light-requiring process. AB - A glucose-tolerant strain of Synechocystis sp. strain 6803 will not grow on glucose under complete darkness unless given a daily pulse of white light, typically 5 min of 40 mumol m-2 s-1 (light-pulsed conditions). The light pulse is insufficient for photoautotrophy, as glucose is required and growth yield is dependent on glucose concentration. Growth rate is independent of fluence, but growth yield is dependent on fluence, saturating at 40 to 75 mumol m-2 s-1. A Synechocystis strain 6803 psbA mutant strain grows under light-pulsed conditions at rates similar to those for the glucose-tolerant strain, indicating that photosystem II is not required for growth. The relative spectral sensitivity of the growth of light-pulsed cultures (growth only in blue light, 400 to 500 nm, maximum at 450 nm) precludes energetic contribution from cyclic electron transport around photosystem I. Pulses of long-wavelength light (i.e., 550 and 650 nm) did not support the growth of Synechocystis strain 6803 and, when supplied before or after a blue-light pulse, did not inhibit blue-light stimulated growth of Synechocystis strain 6803. We conclude that the required blue-light pulse does not support growth via photosynthetic electron transport but appears instead to function as an environmental signal regulating heterotrophic metabolism, cell division, or other photomorphogenic processes. We have termed the growth of Synechocystis strain 6803 pulsed with light and kept otherwise in complete darkness light-activated heterotrophic growth. This observation of a blue-light requirement for the growth of Synechocystis strain 6803 represents a novel blue light effect on the growth of a cyanobacterium. PMID- 1902209 TI - Mannopine and mannopinic acid as substrates for Arthrobacter sp. strain MBA209 and Pseudomonas putida NA513. AB - The characteristics of mannopine and mannopinic acid utilization by Agrobacterium tumefaciens B6S3, Arthrobacter sp. strain MBA209, and Pseudomonas putida NA513 were studied. Strain B6S3 utilized the four mannityl opines, mannopine, mannopinic acid, agropine, and agropinic acid. It also utilized several mannityl opine analogs, which were modified in either the sugar or the amino acid moiety. It utilized mannopine more rapidly after preincubation on mannopine, mannopinic acid, or glutamine than after pregrowth on glucose, mannose, or mannitol. Strains MBA209 and NA513 utilized mannopine and mannopinic acid, but not the other two mannityl opines. They utilized few mannityl opine analogs, sometimes because of failure to utilize the products of initial cleavage of the analog. Utilization of mannopine and mannopinic acid by strain NA513 was strictly dependent on prior growth on these substrates. A spontaneous regulatory variant of strain NA513 remained unable to utilize most of the mannityl opine analogs. Glutamine, mannose, and several analogs had no inhibitory effect on [14C]mannopine utilization by strain NA513. PMID- 1902210 TI - Expression of the Vibrio cholerae gene encoding aldehyde dehydrogenase is under control of ToxR, the cholera toxin transcriptional activator. AB - The toxR gene of Vibrio cholerae encodes a transcriptional activator required for the expression of the cholera toxin genes (ctxAB) and more than 15 other genes encoding secreted or membrane proteins. The latter group includes virulence genes involved in the biogenesis of the TCP pilus, the accessory colonization factor, and such ToxR-activated genes as tagA, mutations in which cause no detectable virulence defect in the suckling mouse model. To analyze the regulation of expression and the structure of tagA, we have cloned and sequenced about 2 kb of DNA upstream from a tagA::TnphoA fusion. While the portion of the tagA gene product examined presented no extensive similarity to any known protein, the amino acid sequence deduced from an open reading frame (designated aldA) located upstream from and in opposite orientation to tagA was highly similar to the sequences of eukaryotic aldehyde dehydrogenases. An assay of aldehyde dehydrogenase activity in extracts of a wild-type V. cholerae strainand an aldA mutant confirmed that aldA encodes an aldehyde dehydrogenase. Expression of the aldA gene was studied together with that of tagA in both V. cholerae and Escherichia coli. The expression of both tagA and aldA was environmentally regulated and dependent on a functional toxR gene in V. cholerae, but neither promoter was activated by ToxR in E. coli, suggesting that expression of tagA and aldA requires an additional transcriptional activator besides ToxR. The aldA gene is the first example of a gene encoding a cytoplasmic protein that is under the control of ToxR, and this suggests that metabolic enzymes may constitute novel members of virulence regulons in bacteria. PMID- 1902211 TI - Heterospecific expression of misrepair-enhancing activity of mucAB in Escherichia coli and Bacillus subtilis. AB - Enterobacterial plasmid genes mucAB, which possess error-prone repair activity, were cloned and sequenced independently of a sequence previously determined (K.L. Perry, S.J. Elledge, B.B. Mitchell, L. Marsh, and G.C. Walker, Proc. Natl. Acad. Sci. USA 82:4331-4335, 1985). The survival- and mutation-enhancing activities of mucAB ligated to the MLSr promoter of a Bacillus subtilis plasmid in the shuttle vector pTE22R were expressed in B. subtilis as well as in Escherichia coli after mutagenic treatment. mucAB fragments with 5' deletions of various lengths up to the base sequence encoding Ala-26-Gly-27, the putative RecA-mediated cleavage site of the MucA protein, showed mutation-enhancing activity for noninducible lexA3 E. coli when ligated to the MLSr promoter in frame. This activity was lost by extending the deletion downstream. The formations of MucA and MucB proteins in B. subtilis and E. coli were demonstrated by Western blot (immunoblot) analysis. MucA cleavage in Rec+ B. subtilis was observed only after treatment with an alkylating agent and was not observed in RecA- and RecE- strains, whereas in E. coli cleavage was observed in Rec+ cells after treatment with either mitomycin C or an alkylating agent but was not detected in RecA- cells. Common activity of B. subtilis Rec and E. coli RecA in the induction of mutants is suggested. PMID- 1902212 TI - Functional significance of overlapping transcripts of crtEF, bchCA, and puf photosynthesis gene operons in Rhodobacter capsulatus. AB - The Rhodobacter capsulatus crtEF, bchCA, and puf operons each encode products that function together to produce photosynthetic pigment-protein complexes. The crtEF operon encodes two enzymes of the carotenoid biosynthetic pathway, the bchCA operon encodes two enzymes of the bacteriochlorophyll biosynthetic pathway, and the puf operon contains six genes, four of which are known to code for proteins that bind pigment cofactors and position them in the intracytoplasmic membrane. These operons are adjacent on the chromosome and are transcribed in the same direction. Although each of these operons can be expressed from its own promoter, it is possible for transcription to begin at the crtEF promoter and continue through the bchCA and puf operons. We herein present the results of experiments which demonstrate that this overlapping transcriptional arrangement is important for establishment of normal levels of transcripts of the bchCA and puf operons and that read-through transcription from the bchCA operon contributes significantly to the expression of a pufB'::lac'Z gene fusion. Growth studies of crtF and bchC interposon mutants show that this read-through transcription is necessary for efficient transition from respiratory to photosynthetic growth modes. PMID- 1902213 TI - Control of transcription of the Bacillus subtilis spoIIIG gene, which codes for the forespore-specific transcription factor sigma G. AB - The Bacillus subtilis spoIIIG gene codes for a sigma factor termed sigma G which directs transcription of genes expressed only in the forespore compartment of the sporulating cell. Use of spoIIIG-lacZ transcriptional fusions showed that spoIIIG is cotranscribed with the spoIIG operon beginning at t0.5-1 of sporulation. However, this large mRNA produced little if any sigma G, and transferring the spoIIIG gene without the spoIIG promoter into the amyE locus resulted in a Spo+ phenotype. Significant translation of spoIIIG began at t2.5-3 with use of an mRNA whose 5' end is just upstream of the spoIIIG coding sequence. Synthesis of this spoIIIG-specific mRNA was not abolished by a deletion in spoIIIG itself. Similar results were obtained when a spoIIIG-lacZ translational fusion lacking the spoIIG promoter was integrated at the amyE locus. These data suggest that synthesis of sigma G is dependent neither on transcription from the spoIIG promoter nor on sigma G itself but can be due to another transcription factor. This transcription factor may be sigma F, the product of the spoIIAC locus, since a spoIIAC mutation blocked spoIIIG expression, and sequences upstream of the 5' end of the spoIIIG specific mRNA agree well with the recognition sequence for sigma F. RNA polymerase containing sigma F (E sigma F) initiated transcription in vitro on a spoIIIG template at the 5' end found in vivo, as did E sigma G. However, E sigma F showed a greater than 20-fold preference for spoIIIG over a known sigma G dependent gene compared with the activity of E sigma G. PMID- 1902214 TI - Absence of glycosylation on cyanobacterial phycobilisome linker polypeptides and rhodophytan phycoerythrins. AB - The 27-, 30-, and 33-kDa rod linker polypeptides and the 75-kDa core linker of phycobilisomes from the cyanobacterium Synechococcus sp. strain PCC 7942 have been reported to be glycoproteins with carbohydrate contents ranging from 3.2 to 18.8% and composed of N-acetylgalactosamine and glucose (H.C. Riethman, T.P. Mawhinney, and L.A. Sherman, J. Bacteriol. 170:2433-2440, 1988). Synechococcus sp. strain PCC 7942 phycobilisomes were purified extensively, and the linker polypeptides were separated from the phycobiliproteins by precipitation in 1 M NaSCN. Upon hydrolysis, the linker fraction yielded 0.037% glucose and 0.015% galactosamine by weight and no other carbohydrate. Phycobilisome polypeptides separated by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate were subjected to various glycoprotein-specific staining procedures. Linker polypeptides showed very weak concanavalin A binding and no staining by the Schiff-periodate method or by a much more sensitive periodate oxidation-based method. These results indicated that the linker polypeptides are not glycosylated. An earlier report (T. Fujiwara, J. Biochem. 49:361-367, 1961) contended, on the basis of the isolation of sugar-containing peptic chromopeptides from Porphyra tenera R-phycoerythrin, that this red algal phycobiliprotein is a glycoprotein. Analysis of Gastroclonium coulteri R phycoerythrin and Porphyridium cruentum B-phycoerythrin revealed only traces of carbohydrate in these two proteins, 0.36 and 0.14%, respectively. Results of glycoprotein staining of gels suggested that the carbohydrate in the R phycoerythrin preparation is due to a glycoprotein contaminant and that neither red algal phycoerythrin is glycosylated. PMID- 1902215 TI - Expression of regulatory nif genes in Rhodobacter capsulatus. AB - Translational fusions of the Escherichia coli lacZ gene to Rhodobacter capsulatus nif genes were constructed in order to determine the regulatory circuit of nif gene expression in R. capsulatus, a free-living photosynthetic diazotroph. The expression of nifH, nifA (copies I and II), and nifR4 was measured in different regulatory mutant strains under different physiological conditions. The expression of nifH and nifR4 (the analog of ntrA in Klebsiella pneumoniae) depends on the NIFR1/R2 system (the analog of the ntr system in K. pneumoniae), on NIFA, and on NIFR4. The expression of both copies of nifA is regulated by the NIFR1/R2 system and is modulated by the N source of the medium under anaerobic photosynthetic growth conditions. In the presence of ammonia or oxygen, moderate expression of nifA was detectable, whereas nifH and nifR4 were not expressed under these conditions. The implications for the regulatory circuit of nif gene expression in R. capsulatus are discussed and compared with the situation in K. pneumoniae, another free-living diazotroph. PMID- 1902217 TI - Effect of platelet activation on the conformation of the plasma membrane glycoprotein IIb-IIIa complex. AB - Platelet activation converts the membrane GP IIb-IIIa complex into a functional receptor for fibrinogen, but the mechanism is poorly understood. We asked whether induction of receptor competency coincides with a conformational change affecting the spatial arrangement of exoplasmic domains of the IIb and IIIa subunits. Epitopes on these subunits were labeled with monoclonal antibodies conjugated to either a donor fluorescein (FITC) or an acceptor tetramethylrhodamine (TR) chromophore. Then, fluorescence resonance energy transfer (RET) between platelet bound FITC and TR was measured by flow cytometry. In unstimulated platelets, 6-8% RET efficiency was detected between antibody B1B5, bound to GP IIb, and antibody SSA6, bound to GP IIIa, regardless of which antibody served as RET donor. RET was also observed between these antibodies and A2A9, an antibody specific for the GP IIb-IIIa complex. Cell stimulation by thrombin, ADP plus epinephrine or phorbol ester caused up to a 2-fold increase in RET between chromophore-labeled, platelet bound B1B5, SSA6, and A2A9 (p less than or equal to 0.05), suggesting a change in the separation or orientation of these epitopes within the GP IIb-IIIa complex. The activation-related conformational change detected by the increase in RET between antibody B1B5 and SSA6 was independent of receptor occupancy since it was unaffected by the addition of fibrinogen or by the inhibition of fibrinogen binding by the antibody, A2A9, or the peptide, RGDS. In contrast to these results with antibodies bound to different epitopes within GP IIb-IIIa, no RET was observed between FITC-A2A9 and TR-A2A9 bound to different GP IIb-IIIa complexes or between a TR-labeled GP Ib antibody and FITC-labeled GP IIb-IIIa antibodies. These studies demonstrate that platelet activation causes a change in the spatial separation or orientation of exoplasmic domains within GP IIb and IIIa, which may serve to convert this integrin into a functional adhesion receptor. PMID- 1902216 TI - Cloning and characterization of the Pseudomonas aeruginosa lasR gene, a transcriptional activator of elastase expression. AB - We report the discovery of the lasR gene, which positively regulates elastase expression in Pseudomonas aeruginosa PAO1. The lasR gene was cloned by its ability to restore a positive elastase phenotype in strain PA103, a strain which possesses the elastase structural gene (lasB) but fails to synthesize the enzyme. Nucleotide sequence analysis revealed an open reading frame of 716 nucleotides encoding a protein of approximately 27 kDa. A labeled LasR protein of 27 kDa was detected in Escherichia coli by using a T7 RNA polymerase expression system. A chromosomal deletion mutant of the lasR gene was constructed in PAO1 by gene replacement. This mutant (PAO-R1) is devoid of elastolytic activity and elastase antigen. The deduced amino acid sequence of LasR is 27% homologous to the positive activator LuxR of Vibrio fischeri and the suspected activator 28K-UvrC of E. coli. Northern (RNA) analysis of total cellular RNA from PAO1, PAO-R1, and PAO-R1 containing the lasR gene on a multicopy plasmid (pMG1.7) revealed that a functional lasR gene is required for transcription of the elastase structural gene (lasB). PMID- 1902218 TI - The relative catalytic specificities of the large subunit core of Synechococcus ribulose bisphosphate carboxylase/oxygenase. AB - The relative specificities of the carboxylase and oxygenase reactions catalyzed by the recombinant large subunit core (L8) of Synechococcus ribulose 1,5 bisphosphate carboxylase have been determined. The L8 core still retained the ability to catalyze both reactions but at a much reduced turnover rate, about 0.6% of the holoenzyme. The fate of ribulose 1,5-bisphosphate during carboxylation and oxygenation by L8 was compared with the Synechococcus holoenzyme (reconstituted from L8 and recombinant small subunits), the carboxylase from Rhodospirullum rubrum, and that of spinach. The absence of small subunits had no significant effect on the partitioning of the bisphosphate substrate between the two reactions. Thus the course of the two competing reactions is a characteristic of the structural elements that compose the L subunits, whereas the S-subunits exert their effect on factors common to both reactions such as the specificity of the bisphosphate substrate. PMID- 1902219 TI - Biosynthesis of heparin. Enzymatic sulfation of pentasaccharides. AB - Heparin-derived pentasaccharides with the general structures GlcN-GlcA/IdoA-GlcN GlcA/IdoA-GlcN (where GlcA represents D-glucuronic acid and IdoA represents L iduronic acid) and GlcNSO3-GlcA/IdoA-GlcNSO3-GlcA/IdoA- GlcNSO3 (where -NSO3 represents an N-sulfate group) were tested as exogenous sulfate acceptors in incubations with adenosine 3'-phosphate 5'-[35S]phosphosulfate and microsomal enzymes from a heparin-producing mouse mastocytoma. No transfer occurred to the N unsubstituted pentasaccharide containing only L-iduronic acid, but the other three isomers incorporated various amounts of 35S, which was totally present in N sulfate groups. After complete chemical N-sulfation, all four pentasaccharides served as acceptors in O-sulfotransferase reactions and incorporated from 20 to greater than 200 times as much radioactivity as did the nonsulfated parent compounds. The C-6 position of the internal glucosamine unit was labeled preferentially, irrespective of the structures of the adjacent hexuronic acid units. Significant 2-O-35S-sulfation of IdoA units occurred in both -IdoA-Glc NSO3-GlcA- and -GlcA-GlcNSO3-IdoA- sequences, whereas no significant sulfation of GlcA residues was detected. The pentasaccharide GlcNSO3-GlcA-Glc-NSO3-GlcA GlcNSO3 thus can be used as a selective substrate in assays for glucosaminyl-6-O sulfotransferase activity. The antithrombin-binding region, essential for the blood anticoagulant activity of heparin, has been identified as a pentasaccharide sequence with the predominant structure GlcNR(6-OSO3)-GlcA-GlcNSO3(3,6-di-OSO3) ++ +IdoA(2-OSO3)-GlcNSO3(6-OSO3) (where R represents either a sulfate or an acetyl group and -OSO3 represents an O-sulfate/ester sulfate group, with locations of O-sulfate groups indicated in parentheses) (Lindahl U., Thunberg, L., Backstrom, G., Riesenfeld, J., Nordling, K., and Bjork, I. (1984) J. Biol. Chem. 259, 12368-12376). The products of [35S]sulfate transfer to the pentasaccharide GlcNSO3-GlcA-GlcNSO3-IdoA-GlcNSO3 contained molecules with high affinity for antithrombin, corresponding to 0.3-0.5% of the total label. Structural analysis suggested the occurrence of O-[35S]sulfate groups at both C-6 of the nonreducing terminal glucosamine unit and C-3 of the internal glucosamine unit. No products with high affinity for antithrombin were formed from the pentasaccharides that had a different monosaccharide sequence than the binding region; and moreover, these oligosaccharides appeared unable to incorporate glucosaminyl 3-O-sulfate groups. These findings point to the importance of the uronic acid sequence in the generation of the antithrombin-binding region of heparin. PMID- 1902220 TI - Mutations in the small subunit of cyanobacterial ribulose-bisphosphate carboxylase/oxygenase that modulate interactions with large subunits. AB - In the cyanobacterium Anacystis nidulans (Synechococcus PCC6301), ribulose 1,5 bisphosphate carboxylase/oxygenase (Rbu-P2 carboxylase) is composed of eight large subunits and eight small subunits. There are three regions of the small subunit that contain amino acids that are conserved throughout evolution, from bacteria to higher plants. Since the function of the small subunit is not fully understood, site-directed mutagenesis was performed on highly conserved residues in the first and second conserved regions. Ser-16, Pro-19, Leu-21, and Tyr-54 were replaced by Asp-16, His-19, Glu-21, and Ser-54, respectively. Crude extracts containing the recombinant His-19 mutant enzyme indicated that there was little effect on either Rbu-P2 carboxylase activity or interactions between large and small subunits. However, the Asp-16, Glu-21, and Ser-54 mutations showed effects on Rbu-P2 carboxylase activity and the interaction between large and small subunits. The large and small subunits of the Asp-16, Glu-21, and Ser-54 enzymes were found to dissociate during nondenaturing gel electrophoresis or sucrose density gradient centrifugation. However, the dissociated small subunits remained functional and were capable of reconstituting Rbu-P2 carboxylase activity when added to large subunits. These results indicated that Ser-16, Leu-21, and Tyr-54 might play an important role in interactions between large and small subunits of the A. nidulans enzyme. PMID- 1902221 TI - In vitro processing of Drosophila melanogaster 5 S ribosomal RNA. 3' end effects and requirement for internal domains of mature 5 S RNA. AB - 5 S RNA processing in Drosophila melanogaster, the removal of 15 nucleotides from the 3' end of the 135-nucleotide (nt) primary transcript, may play an important role in the regulation of 5 S RNA transport and ribosome assembly. We have uncoupled processing from transcription using gel purified primary transcripts processed in vitro by a cellular S100 extract. The RNA was generated by a homologous transcription system or by a T7 RNA polymerase reaction using a constructed 5 S RNA gene linked to a T7 promoter. In vitro D. melanogaster 5 S RNA processing is heat- and EDTA-sensitive, suggesting a requirement for protein, and produces a 3' end characteristic of mature 5 S RNA. Processing of substrate RNAs with altered 3' ends shows that the 3'-U5 tail (nt 131-135) inhibits the reaction. 30 nt, including all of domain IV and most of domain V, are dispensible for processing, whereas deletions including the base of stem V and all or part of stem III severely inhibit it. Several possible mechanisms are discussed. PMID- 1902222 TI - Endogenous epoxyeicosatrienoyl-phospholipids. A novel class of cellular glycerolipids containing epoxidized arachidonate moieties. AB - By chromatographic and mass spectral techniques we document in rat liver the presence of new classes of glycerophospholipids which contain an epoxyeicosatrienoate moiety, esterified to the glycerol-sn-2 position. These novel lipids are formed in vivo from endogenous precursors and under physiological conditions. Chromatographic resolution followed by hydrolysis and regioisomeric analysis showed that they consist of the 8,9-, 11,12-, and 14,15 epoxyeicosatrienoyl derivatives of phosphatidylcholine, phosphatidylethanolamine, and phosphatidylinositol. Their relative concentrations (micromoles of oxidized lipid/mol of phospholipid) were 70, 85, and 106 for phosphatidylcholine, phosphatidylethanolamine, and phosphatidylinositol, respectively. Chiral analysis of the fatty acids at sn-2 revealed an enantioselective preference for 8(S),9(R) , 11(S),12(R)-, and 14(R),15(S)-epoxyeicosatrienoates in all three lipid classes. The data suggest a multienzyme process initiated by cytochrome P-450 epoxidation of arachidonic acid followed by ATP-dependent activation to epoxyeicosatrienoyl CoA derivatives and stereoselective lysolipid acylation. These results provide a molecular basis for a potential physiological role of cytochrome P-450 in the biosynthesis of unique cellular glycerolipids and, consequently, in the control of cell membrane structure and function. PMID- 1902223 TI - A 28,000-Da GDP/GTP-binding protein specific to the nuclear envelope. AB - Using a photoaffinity labeling approach to characterize GDP/GTP-binding proteins of the nuclear envelope, we found that several polypeptides of isolated rat liver nuclear envelopes were photolabeled with [alpha-32P]GDP. One of these labeled proteins, which had an apparent molecular mass of 28 kDa (p28), was highly enriched in nuclear envelopes relative to unfractionated nuclei and was not detectable in fractions of mitochondria, cytosol, and endoplasmic reticulum membranes by two-dimensional gel electrophoresis. Thus p28 is specific to the nuclear envelope. Chemical extractions showed that p28 was tightly associated with a subfraction of the nuclear envelope enriched in nuclear pore complexes and lamina. Solubilization of p28 required buffers containing 1% octylglucoside and at least 300 mM KCl. Photolabeling of p28 was specific for GTP and GDP, since no other guanine or adenine nucleotide tested was able to compete efficiently with [alpha-32P]GDP for photolabeling. Added magnesium or manganese cations were not required for photolabeling of p28, and labeling was substantially inhibited with 10 mM MgCl2, 1 mM MnCl2, and KCl concentrations greater than 150 mM. Sucrose density centrifugation showed that detergent-solubilized p28 had a S value of 2.5. The properties of p28 described in this study suggest that it may have a role in functions of the pore complex or lamina. PMID- 1902224 TI - Purification of GTPase-activating protein specific for the rho gene products. AB - A GTPase-activating protein specific for the rho gene products (rho-GAP) was purified from the cytosol of bovine adrenal gland. Purification procedures consisted of ammonium sulfate fractionation, chromatographies on columns of phenyl-Sepharose and CM-Sepharose, gel filtration on a TSK-gel G3000SW, and Mono S fast protein liquid chromatography. By these procedures the activity was purified about 36,000-fold with a recovery of 0.6%. The final preparation showed a major protein band at Mr 28,000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis and stimulated GTP hydrolysis by the purified rho A protein in a time- and dose-dependent manner. No stimulation was found for ras p21. The ADP ribosylation on the rho protein by botulinum C3 exoenzyme did not affect its interaction with the purified rho-GAP. PMID- 1902225 TI - Evidence for a substrate-binding subsite in ribonuclease T1. Crystal structure of the complex with two guanosines, and model building of the complex with the substrate guanylyl-3',5'-guanosine. AB - The enzyme ribonuclease T1 cleaves single-stranded RNA at the 3'-side of guanosine. The structure of the complex with two guanosines has been analyzed at 1.8-A resolution and refined to a crystallographic R value of 14.0%. One guanosine occupies the guanosine recognition site as observed in previously analyzed complexes of ribonuclease T1 with guanosine phosphates. The other is bound to a base-unspecific subsite marking the binding locus of the nucleoside 3' proximal to guanosine in a cleavable RNA chain. The positions of the guanosine bound to the recognition site and of the guanine base at the subsite were used to guide model building of the substrate guanylyl-3',5'-guanosine bound to the active site of ribonuclease T1. After energy minimization and a 7-ps stochastic dynamics simulation, a plausible model of the enzyme-substrate complex was obtained which may serve as a reference point in consideration of the mechanisms of RNA hydrolysis by ribonuclease T1. PMID- 1902226 TI - Purine nucleoside phosphorylase. Allosteric regulation of a dissociating enzyme. AB - Purine nucleoside phosphorylase (EC 2.4.2.1) from bovine spleen is a trimeric enzyme that readily dissociates to the monomer. Dilution of enzyme from 20 to 0.02 microgram of protein/ml is accompanied by a greater than 50-fold increase in the specific activity (vtrimer = 0.23 nmol/min/microgram; vmonomer = 12.5 nmol/min/micrograms). Gel permeation chromatography in the presence of the substrate phosphate shows the enzyme to be predominantly trimeric at 50 mM Pi and predominantly monomeric at 100 mM Pi, when experiments are done at 24 degrees C. No significant dissociation was observed at 4 degrees C with Pi or at either temperature with the substrate inosine. As measured by dissociation, the L0.5 for Pi is 88 mM and thus significantly higher than the Km of 3.1 mM for Pi. Enzyme activity as a function of phosphate concentration showed negative cooperativity, but the conformational response measured by the change in native Mr during dissociation showed positive cooperatively toward Pi. These data support a model for two separate phosphate binding sites on the enzyme. The activity and stability of purine nucleoside phosphorylase are quite sensitive to the concentration of the enzyme as well as appropriate substrates. Although the monomer is interpreted as being a fully active form of the enzyme, the data in general are most consistent with the enzyme functioning in vivo as a regulated trimer. PMID- 1902227 TI - Peptidyl-alpha-hydroxyglycine alpha-amidating lyase. Purification, characterization, and expression. AB - The production of alpha-amidated peptides from their glycine-extended precursors is a two-step process involving the sequential action of two catalytic domains encoded by the bifunctional peptidylglycine alpha-amidating monooxygenase (PAM) precursor. The NH2-terminal third of the PAM precursor contains the first enzyme, peptidylglycine alpha-hydroxylating monooxygenase (PHM), a copper, molecular oxygen, and ascorbate-dependent enzyme. The middle third of the PAM precursor contains the second enzyme, peptidyl-alpha-hydroxyglycine alpha-amidating lyase (PAL). The COOH-terminal third of the PAM precursor encodes a transmembrane domain and a hydrophilic domain that may form a cytoplasmic tail. Antisera to a peptide within the PAL domain were used to identify a 50-kDa protein as the major form of PAL in bovine neurointermediate pituitary granules. This 50-kDa PAL protein was purified and found to begin at Asp434 of bPAM, indicating that it could arise through endoproteolytic cleavage of the bPAM precursor at Lys432 Lys433. With alpha-N-acetyl-Tyr-Val-alpha-hydroxyglycine as the substrate, PAL exhibits a pH optimum of 5.0; enzymatic activity is inhibited by high concentrations of salt but is relatively resistant to thiol reagents and urea. PAL activity is inhibited by EDTA and restored by a number of divalent metals, including Cd2+, Cu2+, Zn2+, and Ca2+. Kinetic studies using alpha-N-acetyl-Tyr Val-alpha-hydroxyglycine indicate that PAL has a Km of 38 microM and a turnover number of 220/s. Expression vectors encoding only the soluble PHM domain or the PAM precursor from which the PHM domain had been deleted were constructed. hEK293 cells transfected with the PHM vector exhibited a 10-fold increase in secretion of PHM activity with no PHM activity detectable in control or transfected cells. hEK293 cells transfected with the PAL vector exhibited a 2-fold increase in secretion of PAL activity and a 15-fold increase in cellular PAL activity. Most of the PAL activity produced by the transfected cells remained membrane associated. PMID- 1902228 TI - A barbiturate-regulated protein binding to a common sequence in the cytochrome P450 genes of rodents and bacteria. AB - Analyses of the 5' regulatory sequences of genes encoding barbiturate-inducible cytochromes P450BM-1 and P450BM-3 from Bacillus megaterium and of the 5' sequences of genes for barbiturate-inducible P450b and P450e of the rat revealed a string of 17 base pairs in each of the genes that shared a high degree of sequence identity. Labeled oligonucleotide probes of each of these four sequences were tested in gel retardation assays with protein obtained from B. megaterium grown either in the presence or absence of barbiturates or with protein from nuclear extracts from livers of rats left untreated or injected with phenobarbital. Each of the four 17-mers bound strongly to a single protein from bacteria grown in the absence of barbiturates, but this binding was dramatically reduced with protein from pentobarbital- or phenobarbital-grown cells. Conversely, the probes complexed weakly to one protein band from nuclear extracts from untreated rats but much more strongly with protein from phenobarbital treated rats. Similar effects could be obtained by prolonged incubation with phenobarbital of either soluble protein from the bacteria grown in the absence of barbiturates or nuclear extract protein from untreated rats. Deletion analysis of the 5'-flanking region of the P450BM-1 gene of B. megaterium revealed a putative repressor binding site located within a 24-base pair DNA segment that included the 17-base pair sequence involved in barbiturate-regulated protein binding. PMID- 1902229 TI - c-fos and c-jun are induced by muscarinic receptor activation of protein kinase C but are differentially regulated by intracellular calcium. AB - It has become increasingly clear that agents classically thought to act as neurotransmitters can also alter gene expression. To understand the early events by which neurotransmitters could effect genetic responses, we have studied the induction of two immediate early genes, c-fos and c-jun. These genes encode proteins that form a dimeric complex (AP-1) active as a transcriptional factor. Using the stable acetylcholine analog carbachol to activate muscarinic receptors (mAChR) in a glial cell line (1321N1), we show that c-fos and c-jun mRNA levels are transiently increased, reaching a maximum at 30 min after agonist addition. Experiments in which the actions of carbachol are blocked by adding atropine at various times demonstrate that only 1.5 min of agonist stimulation is needed to give maximal increases in c-fos or c-jun mRNA at 30 min. These results suggest that events previously shown to occur in the first minute of mAChR occupation (the mobilization of intracellular Ca2+, activation of protein kinase C) are sufficient for induction of these immediate early genes. In cells in which protein kinase C has been down-regulated, carbachol no longer stimulates c-fos or c-jun expression, indicating a critical role for protein kinase C in these responses. In cells loaded with bis-(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) to buffer increases in cytosolic [Ca2+], mAChR-mediated induction of c-fos is markedly reduced; in contrast there is enhanced c-jun expression. The strong enhancement of c-jun induction by carbachol in BAPTA-treated cells is due at least in part to mRNA stabilization. Experiments using phorbol ester (phorbol 12-myristate 13-acetate) in combination with the Ca2+ ionophore ionomycin confirm that activation of protein kinase C induces c-fos and c-jun expression and that a concomitant increase in cytosolic [Ca2+] potentiates the induction of c-fos while repressing that of c-jun. The data suggest that the ability of neurotransmitters or growth factors to mobilize Ca2+ would modulate the effect of concomitant protein kinase C activation on AP-1 generation and consequent target gene expression. PMID- 1902230 TI - Cell cycle-dependent phosphorylation of human DNA polymerase alpha. AB - The expression of DNA polymerase alpha, a principal chromosome replication enzyme, is constitutive during the cell cycle. We show in this report that DNA polymerase alpha catalytic polypeptide p180 is phosphorylated throughout the cell cycle and is hyperphosphorylated in G2/M phase. The p70 subunit is phosphorylated only in G2/M phase. This cell cycle-dependent phosphorylation is due to cell cycle-dependent kinase(s) and not to phosphatase(s). In vitro evidence indicates the involvement of p34cdc2 kinase in the mitotic phosphorylation of DNA polymerase alpha. Tryptic phosphopeptide maps demonstrate that peptides phosphorylated in vitro are identical to those phosphorylated in vivo. DNA polymerase alpha from mitotic cells is found to have lower affinity for single stranded DNA than does polymerase alpha from G1/S phase cells. These results imply that the mitotic phosphorylation of polymerase alpha may affect its physical interaction with other replicative proteins and/or with DNA at the replication fork. PMID- 1902231 TI - Subunit interaction and function of clathrin-coated vesicle adaptors from the Golgi and the plasma membrane. AB - Clathrin in coated vesicles is linked to transmembrane receptors by adaptor protein complexes. The Golgi-associated adaptor complex HA1 is a tetramer, made up of beta', gamma, 47-kDa, and 20-kDa subunits, whereas the tetrameric plasma membrane adaptor, HA2, contains alpha, beta, 50-kDa, and 16-kDa subunits (Ahle, S., Mann, A., Eichelsbacher, U., and Ungewickell, E. (1988) EMBO J. 7, 919-929). Here we report on the structural organization of adaptor subunits as revealed by proteolytic dissection. We show that the beta' and gamma subunits of HA1 are cleaved into 60-67-kDa "trunk" and 32-44-kDa "head" fragments. Interactions between adaptor subunits involve the trunk domains only. In overall organization of their domains, the Golgi and plasma membrane adaptors are very similar. The similarity encompasses also the location of phosphorylated serine residues in the alpha a, beta, beta', and gamma subunits, which are found in the head domains in all cases. In the alpha a and beta subunits they probably occur in the proline- and glycine-rich hinge region, which connects the head to the trunk. Identical adaptor fragments were obtained by controlled digestion of clathrin-coated vesicles. Under conditions that did not affect the integrity of the clathrin heavy chain, the adaptor head fragments were always quantitatively released from coated vesicles. The release of the bulk of the adaptors occurred concomitantly with the cleavage of their beta-type subunits (beta and beta') and under buffer conditions that prevent aggregation of adaptors. These observations taken together with the results of reconstitution experiments confirm and extend previous data (Ahle, S., and Ungewickell, E. (1989) J. Biol. Chem. 264, 20089 20093) which suggested that adaptors attach to clathrin through their beta-type (beta and beta') subunits. Moreover, high affinity interaction between adaptors and clathrin requires the participation of regions from both the head and trunk domains of the beta-type subunits. PMID- 1902232 TI - Insulin and platelet-derived growth factor stimulate phosphorylation of the c-raf product at serine and threonine residues in intact cells. AB - We have examined the phosphorylation of the serine threonine kinase, the product of c-raf proto-oncogene in response to insulin or platelet-derived growth factor in intact cells. Both insulin and platelet-derived growth factor stimulated phosphorylation of the c-raf protein about 2- to 3-fold. The phosphorylation occurred exclusively on serine and threonine residues; phosphotyrosine was not detected. In immune-complex kinase assays, treatment with insulin, and platelet derived growth factor increased autophosphorylation of the c-raf kinase, suggesting activation of its kinase activity. To investigate whether the phosphorylation of the c-raf protein in intact cells results from an autophosphorylation event or from the phosphorylation by other cellular kinase(s), we replaced lysine 375 in the putative ATP-binding domain of the c-raf protein with alanine using oligonucleotide site-directed mutagenesis and expressed the mutated protein in NIH3T3 cells. The substitution resulted in the inactivation of the serine/threonine-specific autophosphorylation in immune complex kinase assays. In intact cells, however, although phosphorylation of the mutant protein in response to insulin and platelet-derived growth factor occurred to a lesser extent than that of the wild-type protein, the phosphopeptide maps were indistinguishable. These results suggest that serine threonine phosphorylation might be responsible for the activation of c-raf kinase upon treatment of cells with insulin and platelet-derived growth factor, and most of the phosphate associated with the c-raf protein results from its phosphorylation by as yet uncharacterized cellular serine/threonine kinase(s). PMID- 1902233 TI - Clathrin domains involved in recognition by assembly protein AP-2. AB - The domains on clathrin responsible for interaction with the plasma membrane associated assembly protein AP-2 have been studied using a novel cage binding assay. AP-2 bound to pure clathrin cages but not to coat structures already containing AP that had been prepared by coassembly. Binding to preassembled cages also occurred in the presence of elevated Tris-HCl concentrations (greater than or equal to 200 mM) which block AP-2 interactions with free clathrin. AP-2 interactions with assembled cages could also be distinguished from AP-2 binding to clathrin trimers by sodium tripolyphosphate (NaPPPi), which binds to the alpha subunit of AP-2 (Beck, K., and Keen, J. H. (1991) J. Biol. Chem. 266, 4442-4447). At concentrations of 1-5 mM, NaPPPi blocked clathrin-triskelion binding; in contrast, interactions with cages persisted in the presence of 25 mM NaPPPi. To begin to identify the region(s) of the clathrin molecule important in recognition by AP-2, clathrin cages were proteolyzed to remove heavy chain terminal domains and portions of the distal leg as well as all of the light chains. AP-2 bound to these "clipped cages"; however, unlike the interaction with native cages, binding of AP-2 to clipped cages was sensitive to the lower concentrations of both Tris HCl and NaPPPi which disrupt interactions of AP-2 with clathrin trimers. Reconstitution of the clipped cages with clathrin light chains did not restore resistance of AP-2 binding to Tris-HCl. We conclude that one binding site for AP 2 resides on the hub and/or proximal part of the clathrin triskelion whereas a second site is likely to involve the terminal domain and/or distal leg; the second site is manifested only in the assembled lattice structure. We suggest that these two distinct binding interactions may be mediated by the two unique large subunits within the AP-2 complex, acting sequentially during assembly. PMID- 1902234 TI - Prevention of bioprosthetic heart valve tissue calcification by charge modification: effects of protamine binding by formaldehyde. AB - Calcification is the principal cause of the clinical failure of bioprosthetic heart valves (BHV). Calcification occurs through an interaction of host and implant factors, mainly younger age and glutaraldehyde pretreatment, respectively. The hypothesis of this work was that an impaired balance between positively and negatively charged amino acids, due to the reaction with Lys and Hyl tissue-collagen residues, expose affinity sites to Ca++. We further hypothesized that regardless of the cause(s) of BHV calcification, positive charge modification of the tissues will prevent their propensity to calcify. Modification of BHV tissue was obtained by covalently binding protamine sulfate, a polybasic peptide, via formaldehyde and subsequent glutaraldehyde tissue crosslinking. Protamine-bound tissue exhibited stability properties (shrinkage temperature and resistance to collagenase digestion) similar to BHV tissue. Protamine-treated tissue was less permeable to Ca++, and reduced staining was observed with positively charged dyes, indicating the presence of positively charged functional groups in the modified tissue. Significant prevention of calcification was exhibited by the p-bound tissue in comparison to BHV tissue, 30.9 and 109 micrograms/mg calcium, respectively, after 30 days of subdermal implants in rats. The modification procedure resulted in stable, covalent links of approximately 10% w/w protamine with undiminished anticalcification properties, even after 1 year storage. The results support our hypotheses, and orthotopical heart valve replacements are required in order to completely evaluate the treatment efficacy and biocompatibility. PMID- 1902235 TI - [An all-night electroencephalographic study on grand mal epilepsy in childhood. A longitudinal study on the incidence of epileptic discharges with treatment and the comparison between all-night electroencephalography and standard sleep activated electroencephalography]. AB - In order to quantify changes in epileptic discharges during the course of phenobarbital (PB) therapy, 8 children with generalized tonic-clonic seizure (GTC) corresponding to sleep epilepsy as defined by Janz were given PB, and their all-night EEGs were obtained by means of a polygraph with simultaneous measurement of the blood concentration of PB. EEGs were recorded before the treatment commenced and 3 days, 14 days, one month, 6 months, one year, 1.5 and 2 years after the beginning of the treatment. For each child, the number of epileptic discharges during sleep was determined. The incidence of epileptic discharges (total number of epileptic discharges during sleep divided by total sleep time) was calculated, and changes during the course of the treatment were examined. In addition, the findings (pattern of epileptic discharges) obtained through standard short-time EEG recordings were compared with those obtained through all-night EEG recordings in terms of the incidence of epileptic discharges during the first S1-S2 after the subject had fallen asleep and the incidence of epileptic discharges during all stage of S1 and S2 while asleep. There were two different patterns of changes in the incidence of epileptic discharges. In 5 of the 8 children, the incidence was decreased at the initial stages of treatment, but it began to increase about one month later, returning to the baseline level (re-increased type). In the remaining 3 children, the incidence decreased favorably after the beginning of treatment, reaching nil within one year (simple decrease type). The incidence of epileptic discharges was found to be decreased in all 8 children after 3 days of treatment, when the blood PB concentration had not reached the effective level. Standard EEG and all-night EEG revealed similar patterns of epileptic discharges. PMID- 1902236 TI - [A design of the electrophysiological model on the action of antiarrhythmic agent in hypoxic condition and the electrophysiological study of flecainide]. AB - Pharmacologic action of antiarrhythmic agents in hypoxia was studied with the microelectrode using the guinea pig papillary muscle. Tyrode solution saturated with 95% O2 and 5% CO2 provided normoxic condition and that with 95% N2 and 5% O2 hypoxic condition. The parameters measured were as follows: 1) Vmax: the maximum rate of rise of the action potential, 2) ERP: effective refractory period, 3) ERP/APD90%: the ratio of effective refractory period to action potential duration at 90% repolarization. [1] When the papillary muscle was perfused more than 15 minutes with the hypoxic solution, irreversible changes ensued inevitably. Accordingly, a perfusion with the hypoxic solution for 15 minutes was succeeded by that with the normoxic solution for 30 minutes. This was then followed by another perfusion with the hypoxic solution. [2] Flecainide was examined in 7 cases. The rate of the depression of Vmax by flecainide was significantly (p less than 0.01) increased in hypoxia (16.3 +/- 4.2%) than in normoxia (7.4 +/- 2.0%). There were no significantly differences in the rate of the change of ERP between both conditions. The rate of ERP/APD90% was significantly (p less than 0.01) increased by flecainide during hypoxia (2.2 +/- 0.8%) than during normoxia (0.1 +/- 2.1%). [3] The depression of Vmax and the increase of ERP/APD90% by flecainide occurred in a dose-dependent manner in normoxia. it was concluded that the depression of Vmax by flecainide over the concentration of 2 micrograms/dl were ascribed to its inhibitory effect on the fast Na channel and that its depressive effects were enhanced during hypoxic condition. This inhibitory action was regarded as the main antiarrhythmic action of flecainide. From the above results, it is expected that flecainide could be effective in the treatment of ventricular arrhythmias in the ischemic heart disease. PMID- 1902237 TI - Cortical reflex myoclonus. A study of the relationship between giant somatosensory evoked potentials and motor excitability. AB - The excitability cycles of the N1-P1-N2 waveforms of the scalp-recorded somatosensory evoked potential (SEP) and of the long-latency, cortical loop reflex electromyographic (EMG) activity were studied in two patients with cortical reflex myoclonus. Long-latency cortical loop reflex EMG activity in the thenar muscles and giant SEPs occurred following median nerve stimulation. The excitability cycle of the EMG paralleled that of the SEP. There was an initial period of attenuation of SEP and EMG amplitude at interstimulus intervals (ISIs) of less than 40 ms followed by a period of amplitude enhancement at an ISI of up to 200 ms followed by a second period of attenuation. The excitability cycle is abnormal and the SEP and EMG amplitude changes parallel each other. It is therefore likely that a common mechanism determines the abnormal excitability cycle. The substrate for this mechanism is unknown and may be diffuse or restricted. Oral 5-hydroxytryptophan (5-HTP) in therapeutic doses altered the SEP excitability cycle. 5-HTP did not attenuate the giant SEPs but did attenuate the long-latency reflex EMG. Therefore, 5-HTP's site of action may be different from the substrate underlying the mechanism that results in the giant SEPs. Additionally, spinal latency reflex EMG activity occurred following treatment with 5-HTP but was absent when the patient discontinued 5-HTP. PMID- 1902238 TI - Evaluation of a potential interaction between erythromycin and glyburide in diabetic volunteers. AB - The effects of erythromycin on the pharmacokinetics and pharmacodynamics of glyburide were evaluated in 12 patients with non-insulin-dependent diabetes mellitus (fasting blood glucose levels 140-280 mg/dL), who received 4 days of treatment with erythromycin base (333 mg administered orally every 8 hr) and a control treatment in a randomized crossover design; 5 mg glyburide was administered on day 4 of each study period. Serum glyburide concentrations were determined by high-performance liquid chromatography. Peak serum glyburide concentrations were increased by 18%, and mean time to peak glyburide concentrations (Tmax) decreased from 4.9 to 3.0 hours during erythromycin treatment; only the difference in Tmax was statistically significant. No significant effects on glyburide clearance were observed. No significant differences in glucose clearance after carbohydrate loads were observed between erythromycin + glyburide and glyburide treatments. These data show that oral erythromycin base treatment does not affect glyburide metabolism but does affect the rate of glyburide absorption. This effect may be mediated by the stimulation of gastric motility by erythromycin. The clinical significance of the effects of erythromycin on glyburide kinetics appears to be minimal, based on the determinations of serum glucose concentrations. PMID- 1902239 TI - Feeding the terminally ill: dietitians' attitudes and beliefs. AB - Medical, legal, and bioethical discussions have focused on withholding or withdrawing nourishment from adults who are terminally ill or in persistent vegetative states, yet few discussions have considered the dietitian's role. In June 1990, the Supreme Court upheld an individual's right to refuse life prolonging procedures, provided those wishes had been clearly documented. This decision, and The American Dietetic Association's 1987 guidelines for feeding the terminally ill, may enable dietitians to evaluate complicated situations regarding feeding and nonfeeding of patients. A survey sent to 590 registered dietitians in The American Dietetic Association's Nutrition Support dietetic practice group resulted in a 42% (n = 250) response rate. In general, dietitians were more willing to discontinue total parenteral nutrition than to discontinue enteral, noninvasive enteral, or oral feedings. They thought that feeding could be discontinued if it causes pain or worsens the condition, if death is imminent, or if the patient has requested that feeding be stopped. University courses and continuing education programs on the ethics and legalities of feeding terminally or critically ill adults will enable dietitians to take active roles in the decision-making process and to promote awareness of relevant issues with patients and families. PMID- 1902240 TI - Dietitians' role in decisions to withhold nutrition and hydration. AB - Decisions to limit nutrition and hydration in irreversibly or terminally ill patients are becoming more frequent in both hospitals and home-care settings. Although clear-cut principles or rules are not always possible, appropriate decisions about any form of life-sustaining treatment, nutrition and hydration included, require conducting a productive moral conversation within the medical management team and/or the institutional ethics committee. In this article, we discuss how dietitians can participate in these medical decisions. PMID- 1902241 TI - A chemical score to evaluate the protein quality of commercial parenteral and enteral formulas: emphasis on formulas for patients with liver failure. AB - Essential amino acids, found in abundance in high-quality dietary protein, are required daily by hospitalized patients and healthy persons to maintain the dynamic process of protein metabolism. One method for assessing dietary protein quality is by determining a diet's chemical score, ie, the ratio of a gram of the limiting amino acid in a test diet to the same amount of the corresponding amino acid in a reference diet (eg, whole-egg protein) multiplied by 100. This investigation used the chemical score to evaluate the protein quality of 9 parenteral and 17 enteral diets commonly used to feed hospitalized patients. Standard parenteral and enteral products (ie, formulas that had not been designed for patients with a specific disease state) had chemical scores that ranged from 46% to 70%. Limiting amino acids were either methionine (plus cysteine) or phenylalanine (plus tyrosine). Products designed for patients with renal failure had the highest scores, which ranged from 85% to 145%. Products that were enriched with branched-chain amino acids for trauma patients had scores that ranged from 38% to 73%. The only product available for patients with pulmonary compromise had a score of 50%. The lowest scores, which ranged from 5% to 13%, were found in products for patients with hepatic failure. All products, except those with chemical scores below 13%, may be fed in relatively small amounts of protein (7 to 33 g) to satisfy the minimum daily requirements of essential amino acids, although such levels would not meet minimal daily nitrogen requirements. We recommend that dietitians use the chemical score to assess the protein quality of parenteral and enteral diets. PMID- 1902242 TI - The alternatives to restraints. AB - Nurses frequently verbalize their ambivalence towards the use of restraints, but have lacked efforts to change or decrease the practice. The decision of whether to use restraints may be based on a perception of threat of safety to self or others, the staff's tolerance levels for behavior, a perception of short staffing, or a knowledge gap of alternative approaches. Ongoing assessment and monitoring changes in physical and cognitive functional abilities, with a carefully detailed plan of rehabilitative and restorative nursing, can deter staff's feelings of having to rely on restraint use for safety. PMID- 1902243 TI - Making the transition to restraint-free care. AB - When implementing a change to restraint-free care, education and communication at all levels of the organization are powerful strategies to overcome resistance. Within each facility, there are at least six identifiable groups, with attitudes based on their educational background, life experiences and perceptions that are targets for change. An anonymous attitudinal survey and sensitivity session serve as effective "unfreezing" tools for all levels of staff to express concerns regarding physical restraints and to recognize the need for change. Change requires a slow, methodical system where specific alternatives are gradually introduced. Success with the easier cases encourages staff to continue efforts with more challenging cases. PMID- 1902244 TI - Double wavelength measurement of 3,3',5,5'-tetramethylbenzidine (TMB) provides a three-fold enhancement of the ELISA measuring range. AB - A rapid, simple method is described which permits a three-fold enhancement of the working range of ELISA procedures using TMB as a substrate. This consists of measuring absorbance values at a wavelength away from the absorption maximum of TMB and using a predetermined multiplication factor. PMID- 1902245 TI - Production and characterization of a human hyperimmune intravenous immunoglobulin against Pseudomonas aeruginosa and Klebsiella species. AB - A hyperimmune globulin for intravenous use (H-IVIG) was prepared from the plasma of donors immunized with Pseudomonas aeruginosa and Klebsiella vaccines. H-IVIG preparations contained substantially higher IgG antibody levels to all nine P. aeruginosa vaccine antigens and to 22 of the 24 Klebsiella vaccine antigens than did commercial IVIG. The H-IVIG was more effective at promoting the opsonophagocytic killing of P. aeruginosa and Klebsiella vaccine serotype strains than normal IVIG. The H-IVIG neutralized greater than 20 times more toxin A than commercial IVIG. Only the H-IVIG offered significant protection against Klebsiella K2 sepsis. The H-IVIG provided significantly better protection against six of the eight P. aeruginosa vaccine serotypes than normal IVIG when compared in a murine burn wound sepsis model. The H-IVIG also protected mice against an Enterobacter aerogenes challenge, whereas normal IVIG was ineffective. PMID- 1902246 TI - Pathology and human immunodeficiency virus expression in placentas of seropositive women. AB - The pathology of term placentas from seropositive human immunodeficiency virus (HIV)-infected and seronegative women was investigated by routine histologic, immunocytochemical, and in situ hybridization techniques. Placentas were evaluated for evidence of villitis, chorioamnionitis, and funisitis. Membranes, trophoblast, and decidua were also examined by immunohistochemistry using monoclonal HIV p24 antibody. Twenty placentas were evaluated by combined immunochemical and in situ hybridization techniques, using a 35S-labeled RNA probe complementary to the 3' long terminal repeat and envelope region of HIV-1. HIV-seropositive placentas did not show significant villitis; however, the incidence of chorioamnionitis increased (P less than .01). HIV antigens and nucleic acids were identified in the trophoblast of 10% of the placentas that also showed chorionitis. Term HIV-positive placentas may show histologic changes that may or may not be directly related to the virus. Analysis of tissues from earlier gestational placentas may prove more informative in clarifying the mechanism of maternal-fetal HIV transmission. PMID- 1902247 TI - Immune cell activation in melioidosis: increased serum levels of interferon-gamma and soluble interleukin-2 receptors without change in soluble CD8 protein. AB - To evaluate immune cell activation in patients with melioidosis, serum samples were assayed for interferon-gamma (IFN-gamma), soluble interleukin-2 receptors (sIL-2R), and soluble CD8 protein (sCD8). Forty patients with sepsis (23 fatal cases, 17 survivors) and 13 with localized disease were studied during acute illness; 12 additional patients were studied after discharge while on maintenance antimicrobial therapy. Serum concentrations of IFN-gamma and sIL-2R were greatly elevated, but sCD8 concentrations were not. These levels increased with disease severity and were associated with fatal outcomes. Macrophage activation by high concentrations of the cytokine IFN-gamma may contribute to pathophysiology and death in septicemic patients. Both IFN-gamma and sIL-2R seem to be predictive of outcome in patients with severe melioidosis and may prove useful in detection of relapse. PMID- 1902248 TI - An outbreak of soft-tissue infections due to Mycobacterium fortuitum associated with electromyography. AB - An outbreak of infections due to Mycobacterium fortuitum associated with electromyography (EMG) is described. During a 6-week period, six patients who received EMG at one facility developed soft-tissue infections manifested by slowly expanding suppurative nodules at sites of needle electrode insertion. M. fortuitum was isolated from five patients; four isolates that were evaluated further were M. fortuitum biovariant fortuitum. EMG procedures were done in one laboratory by one physician and assistant. Standard procedures included use of reusable needle electrodes disinfected with 2% glutaraldehyde and then rinsed with tap water. On recognition of the outbreak, the procedure was changed to include autoclaving of needle electrodes. Active surveillance for 1 year revealed no further cases. M. fortuitum could not be isolated from the laboratory, EMG equipment and reagents, or skin of the medical personnel. The outbreak demonstrates that nontuberculous mycobacterial infection may be associated with EMG. PMID- 1902249 TI - Interferon-gamma enhances the effect of antimalarial chemotherapy in murine Plasmodium vinckei malaria. AB - Most nonimmune patients with Plasmodium falciparum infection are no longer cured by such standard antimalarial drugs as chloroquine. Thus, alternative treatment regimens are necessary. A combination therapy was tested consisting of a subcurative dose of chloroquine and interferon-gamma (IFN-gamma) in BALB/c mice with lethal Plasmodium vinckei malaria. Treatment with either agent alone prolonged median survival by 1-2 days compared with placebo-treated mice. However, a combination of 80 micrograms of chloroquine given at the time of infection plus 1 x 10(4) units of IFN-gamma/day for 11 days (starting 3 days before infection) cured 83% of infected mice. Moreover, these mice showed solid immunity when challenged with the homologous strain of P. vinckei. However, when these mice were infected with the heterologous strain of Plasmodium berghei, the same degree of parasitemia developed as did in P. berghei-infected control mice. Thus, the combination of chemotherapy with the cytokine IFN-gamma leads to substantial improvement of antimalarial treatment and to a rapid development of strain-specific immunity in murine P. vinckei malaria. PMID- 1902250 TI - Percutaneous endoscopic gastrostomy for postoperative rehabilitation after maxillofacial tumor surgery. AB - Despite the progress made in tumor and reconstructive surgery of the maxillofacial region, postoperative problems, such as malnutrition and dysfunction of the oral-oesophageal tract are still encountered. Nutrition via a nasogastric tube often complicates the rehabilitation process of these patients. Percutaneous endoscopic gastronomy (PEG), as opposed to nasogastral feeding, is presented. The technique, possible long-term complications, and the easy usage of the mechanical pump system, are presented. In our study of 40 patients, PEG, objectively, proved useful for functional, esthetic, practical, economical, and psychological reasons. PMID- 1902252 TI - In-vitro activity of ciprofloxacin and other beta-lactam antibiotics against gentamicin- and carbenicillin-resistant isolates of Pseudomonas aeruginosa. AB - The susceptibilities of gentamicin- and carbenicillin-resistant clinical isolates of Pseudomonas aeruginosa to newer beta-lactams, netilmicin and ciprofloxacin were studied by a broth microdilution technique. Imipenem, aztreonam and ceftazidime were active against most of the P. aeruginosa strains with minimum inhibitory concentration (MIC) for 90% of the isolates at clinically achievable levels. Piperacillin, azlocillin, cefotaxime, ceftriaxone, cefsulodin, cefoperazone and netilmicin showed poor activity against these organisms, ciprofloxacin exhibited poor activity, inhibiting only 30% of these strains. PMID- 1902251 TI - Inhibition of the activation of Hageman factor (factor XII) and of platelet aggregation by extracts of Brugia malayi microfilariae. AB - In human filariasis, large numbers of blood-borne microfilariae circulate unimpeded through the blood stream. How intravascular filarial parasites avoid precipitating thrombosis has not been studied in detail. We hypothesized that extracts of Brugia malayi microfilariae would contain factors that inhibit activation of hemostatic mechanisms. Initial studies demonstrated an inhibitor specific for the intrinsic coagulation cascade. The addition of microfilarial extracts to human plasma prolonged the activated partial thromboplastin time in a dose-dependent fashion but did not prolong the prothrombin, thrombin, or Russell's viper venom times. Microfilarial extracts (0.1 mg/ml) completely inhibited activation of Hageman factor (factor XII, at 0.05 U/ml) as measured in an amidolytic assay. Hageman factor previously activated by ellagic acid (factor XIIa) retained full enzymatic activity in the presence of microfilarial extract (0.1 mg/ml). The presence of inhibitory activity in the culture medium of live parasites raises the possibility that microfilariae secrete an inhibitory protein into their local environment. Microfilarial extracts at a final concentration of 0.1 mg/ml also inhibited collagen- and adenosine diphosphate-induced platelet aggregation. Arachidonic acid-induced platelet aggregation was inhibited by microfilarial extracts at a final concentration of 0.6 mg/ml. These results suggest that microfilariae of Brugia malayi, a human filarial parasite, may avoid initiating thrombosis through inhibition of the intrinsic coagulation pathway and platelet aggregation. PMID- 1902253 TI - A double-blind comparison of low-dose intravenous ketamine and methohexital in adults. AB - Two ultralight general anesthetic techniques, one using low-dose ketamine and the other using methohexital as the primary anesthetic agent, were compared for efficacy, safety, and psychomotor recovery in a double-blind fashion for use during third molar surgery. Low-dose intravenous ketamine as the primary anesthetic following premedication with fentanyl and midazolam, and in conjunction with nitrous oxide, appeared to produce less hypoxia, hypercarbia, and apnea than when methohexital was used. No significant differences were noted in heart rate or blood pressure between the techniques. The ketamine technique was universally preferred by the surgeons and anesthesiologists because of superior patient cooperation and airway management. No unpleasant psychomimetic side effects of significance were noted with the use of ketamine. Postoperative recovery took slightly longer in the ketamine group, with patients being judged fit for discharge approximately 10 to 15 minutes later than the patients who received methohexital. PMID- 1902254 TI - [The characteristics of nasopharyngeal carcinoma cell strain against chemotherapeutic agents and cytokines]. AB - The closed relationship between nasopharyngeal carcinoma (NPC) and Epstein-Barr virus (EBV) has been pointed out. However, it still remains unclear whether the EBV becomes a true factor in initiation and promotion in NPC or not, because of difficulty to establish this cancer strain. We succeeded to establish the EBV genome positive cell line (NPC-TY861) in 1986, which had been derived from the tissues of nasopharyngeal carcinoma. In this study, the characteristics of this cell strain were investigated by tests for sensitivity against several kinds of anti-cancerous agents and immuno-activated cells. The sensitivity tests revealed that NPC-TY861 cell line was extremely sensitive to PEP, ADR, VCR, LPA and CDDP with dose dependent manner. Furthermore, this cell strain had similar sensitivity to CDDP derivatives, such as 254-S, NK121, DWA2114R and CBDCA as KB cell strain did, which had been derived from an oral base cancer. The oral base cancer was a poorly differentiated squamous cell carcinoma histopathologically as same as NPC TY861 cell strain. On the other hand, NPC-TY861 cell strain showed no sensitivity to cytokines, TNF and IFN, which have direct anti-cancerous actions. NPC-TY861 cell strain had resistant to NK cells and much more resistant to LAK cells derived from IL-2 than Daudi cell strain did. In order to elucidate the oncogeneous mechanism in NPC, it is indispensable to study the character of this cell strain and it would promise to get a new effective therapeutic method for the patient with NPC, who has bad prognosis. PMID- 1902255 TI - Economic impact of diagnosis-related groups and severity of illness on reimbursement for central nervous system infections. AB - Because the federal government's diagnosis-related group (DRG) classification system for prospective payment has not been widely applied to hospitalized pediatric patients, we analyzed the effectiveness of one DRG category (central nervous system infections) for a single year at a medium-sized children's hospital to control for patients' severity of illness and for hospital reimbursement. Several independent measures of severity of illness (length of stay, duration of fever, Physiologic Severity Index) showed that patients with bacterial meningitis and those with encephalitis (DRG 20) were more ill than those with aseptic meningitis (DRG 21) (p less than 0.001 for each measure). Cost analysis revealed that the hospital was only partially reimbursed for its charges (shortfall of $95,547) and that patients with Medicaid or no insurance accounted for 22% of discharges but 88% of losses. Reimbursement by DRG would have increased payment for DRG 21 but decreased that for DRG 20. If DRGs were applied to pediatric central nervous system infections and used in a prospective payment system, they would accurately predict disease severity between but not within groups, and significant financial losses for children's hospitals would still occur. PMID- 1902256 TI - Phytosterolemia and pseudohomozygous type II hypercholesterolemia in two Chinese patients. PMID- 1902258 TI - Potassium channel activation by cromakalim affects the slow wave type action potential of colonic smooth muscle. AB - The objective was to determine the existence of a glybenclamide-sensitive K+ conductance in intestinal smooth muscle, to study a possible role for this conductance in the generation of colonic slow wave type action potentials and to investigate if modification of this conductance could alter the action potentials and hence colonic motility. Intracellular electrical recording techniques were used to study properties of cells from the network of smooth muscle cells and interstitial cells of Cajal at the submucosal border of the circular muscle layer of the canine colon, where colonic pacemaker activity is generated. Cromakalim, dose dependently, hyperpolarized the cells and decreased the duration of the action potential, thereby inhibiting contractile activity. The upstroke amplitude and the action potential frequency remained unaltered. Glybenclamide did not affect any parameter of spontaneous electrical activity but prevented all effects of cromakalim. Cromakalim seems to act through increase in K+ conductance because the cromakalim-induced hyperpolarization is accompanied by a marked reduction in input resistance, is inhibited by glybenclamide and tetraethylammonium and it is shown that the cromakalim effect does not occur through effects on Na+ or Cl- conductances. Thus, glybenclamide-sensitive K+ conductance exists in colonic smooth muscle; the spontaneous development of slow wave type action potentials in this tissue occurs independent of this conductance. Its existence may provide pharmacological possibilities to affect gastrointestinal motility. PMID- 1902257 TI - Aminoalkylindoles: actions on specific G-protein-linked receptors. AB - Aminoalkylindoles (AAIs) are antinociceptive agents which act through two distinct mechanisms: inhibition of cyclooxygenase and a novel mechanism retained by AAI analogs which do not inhibit cyclooxygenase. This latter mechanism is reflected by inhibition of neuronally mediated contractions in several smooth muscle bioassays. The present studies explored the potential receptor interactions of AAIs in smooth muscle preparations and in rat brain membranes. Experiments in an electrically stimulated mouse vas deferens preparation (MVD) demonstrated that several AAI agonists inhibited neuronally mediated muscle contractions over a wide potency range (0.1-1000 nM) and in a stereospecific manner. Also, a putative AAI antagonist analog selectively attenuated AAI-induced inhibition in the MVD: 10 microM of the antagonist analog produced 16- to 40-fold rightward shifts in the concentration-effect curves for AAI agonists but failed to attenuate the inhibitory actions of several receptor agonists and other pharmacological agents. AAI agonists also inhibited adenylyl cyclase in membranes from rat striatum and cerebellum. AAI agonists inhibited adenylyl cyclase through G-proteins, because AAI-inhibited adenylyl cyclase required GTP, and was not supported by nonhydrolyzable guanine nucleotides. Inhibition of adenylyl cyclase by several AAI agonists was stereospecific and was not blocked by antagonists of several traditional neurotransmitter receptors. The potencies of AAI agonists to inhibit cerebellar adenylyl cyclase were highly correlated (r = 0.97) with their potencies to inhibit contractions of MVD. These results suggest that AAIs bind to specific receptors which are coupled through G-proteins to inhibit adenylyl cyclase. PMID- 1902259 TI - Isolation, physicochemical characterization and preclinical efficacy evaluation of soluble scleroglucan. AB - Herein we describe the isolation, physicochemical characterization and preclinical evaluation of a water-soluble biologic response modifier extracted from Sclerotium glucanicum. Alkaline extraction of insoluble S. glucanicum exopolymers produced a soluble scleroglucan composed of a triple-helical beta-1,3 linked glucopyranose backbone with single beta-1,6-linked glucopyranosyl branches every third subunit. Scleroglucan has a weight average molecular mass of 1.56 x 10(6) Da, a weight average root mean square distance from the center of gravity of the molecule to its farthest elements of 51.8 nm, a polydispersity (weight average molecular mass/number average molecular mass) of 1.83 and intrinsic viscosity of 3.081 dl/g. Scleroglucan (250 mg/kg, intravenously) stimulated in vivo murine macrophage phagocytic activity (66%, P less than .001) and increased in vitro macrophage tumor cytotoxicity against syngeneic tumor targets by 124% (P less than .05). Scleroglucan enhanced (P less than .001) murine bone marrow proliferation in a biphasic manner by up to 328%. Scleroglucan therapy increased survival of mice challenged with syngeneic lymphoma, melanoma or adenocarcinoma. AKR/J mice bearing syngeneic lymphoma (1 x 10(3) cells, intraperitoneally) demonstrated increased (P less than .001) long-term survival (100% vs. 0%, greater than 64 days). C57Bl/6J mice bearing syngeneic melanoma B16 (5 x 10(5) cells, subcutaneously) demonstrated increased long-term survival (64% vs. 0%, P less than .05). C57Bl/6J mice bearing syngeneic adenocarcinoma BW10232 (1 x 10(5) cells, subcutaneously) demonstrated increased (P less than .05) median survival time. In addition, scleroglucan prophylaxis increased resistance of mice to challenge with Staphylococcus aureus, Candida albicans and mouse hepatitis virus A-59. Scleroglucan did not induce toxicity or hepatomegaly. We conclude that: 1) a branched, water-soluble beta-1,3-linked scleroglucan biologic response modifier can be extracted from S. glucanicum; 2) scleroglucan will stimulate immunity, modify experimental neoplastic disease and increase resistance to microbial challenge; and 3) scleroglucan shows promise as an immunopotentiating drug. PMID- 1902260 TI - Differential DNA amplification and copy number control in the hypotrichous ciliate Euplotes crassus. AB - During macronuclear development in hypotrichous ciliated protozoans, several thousand macronuclear DNA molecules are amplified several-hundred fold. We investigated the regulation of this amplification by determining the copy numbers of three different macronuclear DNA molecules in the hypotrichous ciliate Euplotes crassus. Two of the macronuclear DNA molecules were present in approximately 1,000 copies per cell, while the third was present in approximately 6,500 copies per cell. These reiteration levels were achieved either during macronuclear development, or shortly thereafter, and were maintained during vegetative growth. The most abundant macronuclear DNA molecule is present as a single-copy sequence in the micronuclear genome. Thus, its high copy number results from differential amplification. These results indicate that DNA amplification during macronuclear development is regulated individually for each macronuclear DNA molecule. PMID- 1902261 TI - Serum antibodies to Pseudomonas aeruginosa outer-membrane proteins and iron regulated membrane proteins at different stages of chronic cystic fibrosis lung infection. AB - Serum samples collected over periods up to 15 years from nine patients with cystic fibrosis (CF) were investigated by immunoblotting and crossed immuno electrophoresis (CIE) for antibodies to Pseudomonas aeruginosa outer-membrane proteins (OMPs). The earliest antibody response to OMPs was directed against proteins G, H1 and I. Detection by immunoblotting sometimes preceded the CIE response; the appearance of antibodies to the other major OMPs was co-incident with an increase in CIE precipitins. Isolation of the mucoid form of P. aeruginosa was associated with a rapid increase in both precipitin numbers and antibodies detected by immunoblotting. Antibodies to iron-regulated OMPs could be detected in all the serum samples that showed eight or more CIE precipitins but their presence became pronounced only in the advanced stages of disease. The clinical strain used in this study and other isolates from CF patients showed several atypical OMPs, perhaps as a consequence of antibiotic therapy or related to the serum sensitivity of mucoid P. aeruginosa. Their expression in vivo was confirmed by detecting antibodies to them in patients' serum. PMID- 1902262 TI - Interaction between Pseudomonas aeruginosa and Staphylococcus aureus: description of an anti-staphylococcal substance. AB - The presence of Pseudomonas aeruginosa in the sputum of 191 patients with cystic fibrosis was significantly related (p less than 0.0001) to the absence of Staphylococcus aureus. Cross-streaking tests showed that 40 of 50 clinical strains of P. aeruginosa produced substances that inhibited the growth of S. aureus. When incorporated into agar plates, this antibacterial substance(s) inhibited the growth of 177 of 189 strains of nine staphylococcal species, all of 16 methicillin-resistant S. aureus and 27 of 39 strains of six other gram positive genera. The substance(s) did not inhibit 23 strains of seven gram negative genera tested. The antibacterial activity was heat stable and could be extracted into chloroform; activity was retained on Sephadex G-15 (V/Vo approximately 2, Mr less than 500) and eluted as a single peak from high performance liquid chromatography, well separated from pseudomonic acid, pyocyanin and a number of other phenazines. PMID- 1902264 TI - Prospective evaluation of epidural and intravenous administration of fentanyl for pain control and restoration of ventilatory function following multiple rib fractures. AB - To evaluate the efficacy of opiate administration regimens, 32 patients with multiple rib fractures were prospectively randomized to receive either continuous epidural (ED) or continuous intravenous (IV) infusions of fentanyl. Dosage was titrated to individual subjective pain relief. Ventilatory function tests (VFTs), arterial blood gases (ABGs), and visual analog scores were obtained before and after the institution of analgesia. Post-analgesia values were compared with pre analgesia values using a two-tailed paired t-test looking for significant changes produced by the analgesic method. Both methods significantly improved analog pain scores. The ED method produced improvement in both maximum inspiratory pressure (MIP) and vital capacity (VC), whereas IV analgesia only produced improvement in VC. Intravenous fentanyl produced increases in PaCO2 and decreases in PaO2, whereas no significant changes in ABGs were observed with ED fentanyl administration. Side effects were similar between the groups, with pruritus being more pronounced with ED fentanyl administration. The data demonstrate that the continuous ED fentanyl method offers excellent relief of pain and improvement in ventilatory function and has distinct advantages over IV fentanyl administration with respect to changes in ABGs and MIP. The continuous infusion of epidural opiates should be the preferred analgesic method for patients at high risk of developing pulmonary complications following multiple rib fractures. PMID- 1902263 TI - Oxygen uptake and H2O2 production by fermentative Mycoplasma spp. AB - Oxygen uptake and H2O2 accumulation during the metabolism of glucose and glycerol by whole cells, and of L-alpha-glycerophosphate (GP) and NADH by cells lysed with Triton, was determined for the type strains of six fermentative Mycoplasma species. Oxidation of glucose and of NADH by M. mycoides, M. pneumoniae and M. putrefaciens was accompanied by the accumulation of relatively small quantities of H2O2 (less than 0.05 mol/mol O2), though larger quantities (0.17-0.24 mol/mol O2) were produced by M. dispar. M. fermentans and M. canis were distinguished from the other strains used in that O2 uptake in the presence of glucose could not be demonstrated. However, metabolism of glucose was indicated by a reduction in the pH of the suspending medium and lysed cells oxidised NADH with the production of approximately 1.0 mol H2O2/mol O2 taken up. Glycerol was oxidised by all the strains studied except M. fermentans, and large quantities of H2O2 (0.48-1.07 mol/mol O2) accumulated. Cells of the glycerol-oxidising strains, lysed with Triton, oxidised GP with the production of approximately 1.0 mol H2O2/mol O2 utilised, which indicated the presence of a GP oxidase. The importance of H2O2 production as a factor in the pathogenicity of some mycoplasmas might depend upon the availability of glycerol in vivo. PMID- 1902265 TI - PMCs--an alternative to DRGs for trauma care reimbursement. AB - Payments made for inpatient trauma care were compared using two different patient classification systems--Patient Management Categories (PMCs) and Diagnosis Related Groups (DRGs). Two databases were used in this study: 1) estimated costs for all inpatient claims from one large payor for adult injured patients (n = 5,256) treated at 79 acute care facilities (trauma centers and non-trauma centers) in one geographic region; and 2) hospital charges from statewide, all payor Maryland data, including 25,987 adult injured patients. The accuracy of PMCs and DRGs in predicting actual costs was examined by level of injury severity and by types of hospital, trauma center vs. non-trauma center. Level of injury (minor, single significant, multiple significant, and major) were defined and operationalized using PMCs. Overall, both DRG and PMC payment systems were nearly equal to the actual costs associated with all injured patients. This relationship can be designed into the weighting scale used for payment. The distribution of DRG payments by injury severity level, however, is not reflective of the differential resources required to manage each patient type. In particular, multiple injuries and major injuries that require the specialized services of a trauma center were inaccurately categorized by DRGs and systematically underpaid by 21.0% to 39.0% by DRG payment. By contrast, the Patient Management Category System classifies patients into more clinically specific and accurate categories and offers a more equitable method of distributing payments by injury severity. These same relationships were also found at the hospital level, demonstrating the potential for use of PMCs as an equitable and viable alternative. PMID- 1902266 TI - Transvaginal sonography of the endometrium during induced cycles. AB - The thickness and texture of the endometrium as depicted by transvaginal sonography were assessed in 23 patients who underwent a similar ovulation induction protocol including a gonadotropin-releasing hormone analogue (Lupron) and human menopausal gonadotropin (Pergonal). In the 9 patients who conceived, a multilayered endometrium was more frequently present than in the 14 who did not, even though the number of mature follicles, oocytes retrieved and transferred, and estradiol values were similar. PMID- 1902267 TI - Groups survey health care costs, charges. PMID- 1902268 TI - Health access America--strengthening the US health care system. AB - Although Americans remain generally satisfied with the health care provided to them, sufficient access to high-quality, affordable health care for citizens without health care insurance has become an increasing problem in the last decade. Using the policy development process of the American Medical Association, Health Access America was conceived by the Association to improve access to affordable, high-quality health care. The proposal consists of six fundamental principles and 16 key points. This article specifically focuses on the five points that, if enacted into law, would improve access to health care for Americans who are, for various reasons, without health insurance. PMID- 1902269 TI - The 'USHealth Act'. Comprehensive reform for a caring America. PMID- 1902270 TI - Review of a case of tsutsugamushi disease showing myocarditis and confirmation of Rickettsia by endomyocardial biopsy. AB - A patient suffering from tsutsugamushi disease underwent endomyocardial biopsy for the purpose of diagnosis of myocarditis. Proliferation of Rickettsia tsutsugamushi was observed in the vascular endothelial cells of the myocardium. There have been no reports describing the identification of Rickettsia tsutsugamushi endomyocardial biopsy. This report indicates that endomyocardial biopsy may be a useful adjunct to the clarification of myocardial involvement of Rickettsia tsutsugamushi. PMID- 1902271 TI - [The successful use of natural alpha-interferon single therapy in multiple myeloma of IgD (lambda)-type]. AB - We have successfully treated multiple myeloma of IgD (lambda) type [IgD (lambda) MM] by natural alpha-interferon (alpha-IFN) single therapy. A 45 year-old man was admitted to Tokyo Medical College Hospital because of general fatigue in August, 1989. Immunoelectrophoresis, bone marrow biopsy and systemic bone survey revealed IgD (lambda) -MM with Bence Jones (BJ) proteinuria and slightly osteolytic lesions. We started treating him with natural alpha-IFN single therapy. Three months later, serum IgD markedly decreased and BJ proteinuria disappeared. Bone marrow, which had been packed with myeloma cells at the admission, was almost replaced by normal hematopoietic cells. In April 1990, he is still free of disease with only alpha-IFN single therapy. This result might suggest that alpha IFN single therapy is effective for IgD-MM. PMID- 1902272 TI - Intraoperative radiation therapy in the treatment of recurrent carcinoma of the head and neck. PMID- 1902273 TI - Hepatic steatosis due to total parenteral nutrition: the influence of short-gut syndrome, refeeding, and small bowel transplantation. AB - This study was undertaken to determine whether refeeding through the native small intestine or through a small bowel transplant would reverse hepatic steatosis induced by total parenteral nutrition (TPN), and of what influence a coexisting short-gut syndrome is. Three short-gut syndromes of different severity were established in Lewis rats (short-gut I, mild; short-gut II, moderate; short-gut III, severe). TPN was administered for 10 days and the animals were refed for 20 days. A liver biopsy after the TPN period confirmed a mild to moderate fatty infiltration of the liver in all groups. After the refeeding period a second liver biopsy was obtained and no evidence of hepatic steatosis was observed in Groups 1, 2, 3, and 4 (normal Lewis rat, short-gut I, II, and III). The animals in group 5 (short-gut I) received a syngeneic small bowel transplant after discontinuation of TPN. After the refeeding period the liver biopsies showed no evidence of fatty infiltration. The intestinal graft also reversed the nutritional deficiencies which were observed in the animals with short-gut and showed normal body weight gain and nitrogen and fat uptake in comparison to the normal animals (Group 1). These data show that a small bowel graft is capable of reversing the deleterious sequelae of short-gut syndrome as well as the TPN related hepatic steatosis. PMID- 1902274 TI - The effect of low dose dopamine on gut hemodynamics during PEEP ventilation for acute lung injury. AB - Mechanical ventilation with positive end-expiratory pressure (PEEP) diminishes gut and hepatic blood flow and redistributes cardiac output away from the splanchnic circulation. This flow-limited environment can aggravate underlying hypoperfusion and ischemia in the postinjury setting. To examine the effects of low dose dopamine on a lung injury PEEP model of gut hypoperfusion, six anesthetized, splenectomized canines were instrumented with arterial, pulmonary artery, portal vein, and hepatic vein catheters. Electromagnetic flow probes were placed around the hepatic artery and portal vein for continuous flow measurements. Gut and hepatic blood flow, oxygen delivery, oxygen consumption, and extraction ratio were calculated at four time points: baseline, 1 hr after lung injury with oleic acid, 1 hr after ventilation with 10 cm H2O PEEP, and 1 hr after the continuous infusion of dopamine. Portal flow and gut oxygen delivery fell significantly with the infusion of PEEP. These values returned to near baseline levels with the addition of dopamine. Gut oxygen extraction increased from 16 +/- 2% to 35 +/- 3% with PEEP but returned to near baseline with dopamine (20 +/- 4%, P less than 0.01 compared to PEEP). We conclude that dopamine improves blood flow and oxygen delivery to the gut in this flow-limited model. This may preserve splanchnic physiology during PEEP ventilation for acute lung injury. PMID- 1902275 TI - The relationship between severity of illness and hospital length of stay and mortality. AB - To address the question of quantification of severity of illness on a wide scale, the Computerized Severity Index (CSI) was developed by a research team at the Johns Hopkins University. This article describes an initial assessment of some aspects of the validity and reliability of the CSI on a sample of 2,378 patients within 27 high-volume DRGs from five teaching hospitals. The 27 DRGs predicted 27% of the variation in LOS, while DRGs adjusted for Admission CSI scores predicted 38% and DRGs adjusted for Maximum CSI scores throughout the hospital stay predicted 54% of this variation. Thus, the Maximum CSI score increased the predictability of DRGs by 100%. We explored the impact of including a 7-day cutoff criterion along with the Maximum CSI score similar to a criterion used in an alternative severity of illness measure. The DRG/Maximum CSI score's predictive power increased to 63% when the 7-day cutoff was added to the CSI definition. The Admission CSI score was used to predict in-hospital mortality and correlated R = 0.603 with mortality. The reliability of Admission and Maximum CSI data collection was high, with agreement of 95% and kappa statistics of 0.88 and 0.90, respectively. PMID- 1902276 TI - Investigating early readmission as an indicator for quality of care studies. AB - Readmission to a hospital shortly following a previous discharge may be viewed as an adverse outcome of care. Consequently, early readmission represents a potentially useful indicator for monitoring quality. While a number of recent research studies have focused on this issue, several important questions concerning appropriate use of early readmission as a quality of care indicator remain to be addressed. In this article, using data on all discharges for 1 year from 18 hospitals, several of these questions are investigated. Specifically, whether the significant predictors of readmission risk are different for different types of cases (defined using DRGs), whether case severity is an important predictor of readmission risk, whether readmission risks differ systematically with hospital size and other characteristics, whether readmission risk is a function of patients' lengths-of-stay, and whether readmission risk is influenced by whether or not patients are discharged home or into organized care environments are explored. For this study, the focus is on patients who experienced unplanned readmissions to acute care hospitals within 31 days of a prior discharge. The Patient Management Category classification system and ICD-9 CM diagnosis and procedure codes are used to identify, and then exclude from consideration, those readmissions that occurred as part of an appropriately planned sequence of care. In each of 22 sets of related DRGs, analysis of unplanned readmissions indicates that severity/complexity is an important risk factor for early readmission and that clinical and other risk factors differ for different DRG groups. Thus, in future studies of early readmissions, researchers will need to control for both the type (e.g., DRG) and severity/complexity of individual cases. In examining relationships between early readmission and hospital characteristics, no consistent patterns suggestive of quality of care problems were detected. PMID- 1902277 TI - Have hospital inpatient cost containment programs contributed to the growth in outpatient expenditures? Analysis of the substitution effect associated with hospital utilization review. AB - The rapid increase in outpatient expenditures has been the focus of growing attention in recent years. This increase has corresponded with public and private efforts to contain hospital inpatient costs, prompting some analysts to suggest that outpatient expenditure growth is the result of a substitution effect; that is, the substitution of outpatient for inpatient care associated with hospital cost containment programs. Claims data on 43 privately insured groups that adopted utilization review (UR) during the latter part of 1984 or early 1985 were analyzed, comparing outpatient expenditures before and after adoption of hospital inpatient UR to quantify the substitution effect associated with UR. UR was not associated with higher physician office expenditures nor with higher outpatient diagnostic expenditures. UR was related to significantly higher hospital outpatient department expenditures. On average, these expenditures were approximately 20% higher (P = 0.01) after the adoption of UR. However, outpatient department expenditures of the groups analyzed represented a fairly small percentage of total medical expenditures; hence, the absolute expenditure increase was quite modest, on the order of $9 per insured person per year. This analysis, admittedly limited in scope, suggests that UR is associated with a measurable substitution effect. It is likely that inpatient hospital cost containment programs have resulted in some substitution of outpatient for inpatient care and thus have played a role in fostering outpatient expenditure growth during recent years. PMID- 1902278 TI - Development and application of a population-oriented measure of ambulatory care case-mix. AB - This article describes a new case-mix methodology applicable primarily to the ambulatory care sector. The Ambulatory Care Group (ACG) system provides a conceptually simple, statistically valid, and clinically relevant measure useful in predicting the utilization of ambulatory health services within a particular population group. ACGs are based on a person's demographic characteristics and their pattern of disease over an extended period of time, such as a year. Specifically, the ACG system is driven by a person's age, sex, and ICD-9-CM diagnoses assigned during patient-provider encounters; it does not require any special data beyond those collected routinely by insurance claims systems or encounter forms. The categorization scheme does not depend on the presence of specific diagnoses that may change over time; rather it is based on broad clusters of diagnoses and conditions. The presence or absence of each disease cluster, along with age and sex, are used to classify a person into one of 51 ACG categories. The ACG system has been developed and tested using computerized encounter and claims data from more than 160,000 continuous enrollees at four large HMOs and a state's Medicaid program. The ACG system can explain more than 50% of the variance in ambulatory resource use if used retrospectively and more than 20% if applied prospectively. This compares with 6% when age and sex alone are used. In addition to describing ACG development and validation, this article also explores some potential applications of the system for provider payment, quality assurance, utilization review, and health services research, particularly as it relates to capitated settings. PMID- 1902279 TI - Inappropriate use of transillumination for breast cancer screening--Wisconsin, 1990. AB - The overall effectiveness of early breast cancer detection efforts requires the appropriate use and maintenance of dedicated radiographic mammography systems. However, the effectiveness of early detection efforts can be compromised if proven technology is improperly used and/or maintained or if ineffective technology is successfully marketed as an equivalent or superior alternative to mammography. This report summarizes state and federal responses to the inappropriate use of a nonradiographic imaging technique in a breast cancer screening service advertised and used in Wisconsin in 1990. PMID- 1902280 TI - Outbreak of relapsing fever--Grand Canyon National Park, Arizona, 1990. PMID- 1902281 TI - Gastroenteritis associated with consumption of raw shellfish--Hawaii, 1991. AB - On January 2, 1991, 12 of 24 persons who attended one or more of three New Year's celebrations in Honolulu, Hawaii, had onset of gastrointestinal illness. An investigation by the Epidemiology Branch of the Hawaii Department of Health (HDOH) determined that the only common foods shared by participants were oysters and clams provided by one distributor. PMID- 1902282 TI - Measles outbreak--New York City, 1990-1991. AB - In March 1990, a large measles outbreak began in New York City. Through December 1990, approximately 2500 cases and eight measles-associated deaths were reported. However, since January 1991, transmission has increased; through May 7, more than 2000 cases and nine deaths were reported to the New York City Department of Health (NYCDH) in 1991. PMID- 1902283 TI - Chronic respiratory alkalosis. The effect of sustained hyperventilation on renal regulation of acid-base equilibrium. AB - BACKGROUND: In normal subjects, chronic hyperventilation lowers plasma bicarbonate concentration, primarily by inhibiting the urinary excretion of net acid. The quantitative relation between reduced arterial carbon dioxide tension (PaCO2) and the plasma bicarbonate concentration in the chronic steady state has not been studied in humans, however, and the laboratory criteria for the diagnosis of chronic respiratory alkalosis therefore remain undefined. We wished to provide such reference data for clinical use. Moreover, because chronic hyperventilation paradoxically lowers blood pH still further in dogs with metabolic acidosis, we desired to study the effect of chronic hypocapnia on the plasma bicarbonate concentration (and blood pH) in normal human subjects in whom acidosis had been induced with ammonium chloride. METHODS: Under metabolic balance conditions, we used altitude-induced hypobaric hypoxia to produce chronic hypocapnia in nine normal young men, five of whom received ammonium chloride daily to cause metabolic acidosis (the mean [+/- SE] steady-state plasma bicarbonate level in these five was 12.0 +/- 0.5 mmol per liter). RESULTS: For each decrease of 1 mm Hg (0.13 kPa) in the PaCO2, the plasma bicarbonate concentration decreased by 0.41 mmol per liter in the subjects who started with a normal plasma bicarbonate concentration and by 0.42 mmol per liter in the subjects with acidosis. In contrast to the findings in previous studies of dogs, hypocapnia increased blood pH similarly in both groups; the blood hydrogen ion concentration decreased by about 0.4 nmol per liter for every decrease of 1 mm Hg (0.13 kPa) in PaCO2. CONCLUSIONS: These results provide reference data for the diagnosis of chronic respiratory alkalosis in humans. Although chronic hypocapnia decreased plasma bicarbonate levels similarly in normal subjects with acidosis and without acidosis, the percent reduction in PaCO2 was always greater than the corresponding percent reduction in the plasma bicarbonate concentration. Therefore, as was not true of the response in dogs, the subjects' blood pH always increased with hyperventilation, regardless of the initial plasma bicarbonate concentration. PMID- 1902284 TI - [Minor symptoms in family practice; furuncle, carbuncle and furunculosis]. PMID- 1902285 TI - Iron deficiency in maintenance hemodialysis patients: assessment of diagnosis criteria and of three different iron treatments. AB - The study was carried out in order to evaluate in maintenance hemodialysis (MH) patients: (1) the reliability of serum ferritin (SF) measurement in iron deficiency diagnosis and therapy; (2) the possibility to improve iron stores assessment through laboratory indexes routinely used in clinical practice; (3) the most effective iron deficiency treatment. After a preliminary assessment of SF reference values in 250 healthy volunteers, we studied 72 MH patients divided into three groups according to their SF baseline values: high (group A), normal (group B), low (group C) (normal range 19-191 ng/ml). Each group was further divided into three subgroups receiving three different iron treatments for 6 months: (1) oral administration of 67.5 mg/day of Fe3+ as Fe-ferritin (subgroups A1, B1, C1); (2) oral administration of 60 mg/day of Fe3+ as Fe-chondroitin sulfate (subgroups A2, B2, C2); (3) i.v. administration at the end of each dialytic session of 31 mg of Fe3+ as Fe-gluconate-Na (subgroups A3, B3, C3). The response to the iron therapy was considered positive when the hemoglobin (Hb) and the hematocrit (Ht) increased to greater than or equal to 15% of the baseline values. The rate of positive responses in each subgroup was as follows: A1 0/5, A2 0/5, A3 0/7, B1 2/10, B2 1/6, B3 5/11, C1 1/7, C2 3/7, C3 10/16. We concluded that SF values above 191 ng/ml allow to exclude iron deficiency whereas SF values less than or equal to the normal range are inadequate. In an attempt to improve diagnostic sensitivity we divided patients of subgroup B3 and C3 into responders (R) and nonresponders (NR).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1902286 TI - Schistosoma haematobium-induced glomerular disease: an experimental study in the golden hamster. AB - Information regarding glomerular lesions related to Schistosoma haematobium infection in man or animal are extremely lacking and disputed. The objective of this experimental study was to investigate glomerular lesions in S. haematobium infected golden hamsters. In this work, 53 hamsters were infected with S. haematobium cercariae and 18 animals of similar age and sex served as controls. Hamsters were infected either with 50, 200, 300, 400 or 600 cercariae and sacrified after 8, 9, 10, 14, 18, 24 or 32 weeks. Infected and control hamsters were subjected to laboratory examinations including serum creatinine, serum albumin, total protein, serum cholesterol, total urine protein as well as histopathologic evaluations. Kidney biopsies were examined by light microscopy, indirect immunofluorescence and by electron microscopy. Significant proteinuria, hypoalbuminaemia and hypercholesterolaemia were observed in all but 5 S. haematobium-infected, but in none of the control hamsters. Renal impairment was observed in 5 hamsters. Histopathologic evaluations showed IgG, circulating anodic antigen and circulating cathodic antigen deposits in the renal glomeruli. By electron-microscopic examination, these deposits were seen mainly in the subendothelial, mesangial and paramesangial areas. Amyloid deposits were also seen in the renal glomeruli, tubular basement membrane and in the interstitium. A correlation was found between the extent of amyloid deposition and the duration but not the intensity of schistosomal infection. We have concluded that S. haematobium infection can lead to glomerulopathy in golden hamsters. PMID- 1902288 TI - New drugs being tested for better AIDS treatment. PMID- 1902287 TI - L-dopa stimulates the release of [3H]gamma-aminobutyric acid in the basal ganglia of 6-hydroxydopamine lesioned rats. AB - L-DOPA stimulated the K(+)-induced [3H]GABA (gamma-aminobutyric acid) release from slices of substantia nigra pars reticulata, entopeduncular nucleus, globus pallidus and caudate-putamen isolated from the ipsilateral side of 6 hydroxydopamine-lesioned rats, but the release from ipsilateral subthalamic slices was not affected. In substantia nigra, L-DOPA stimulation (EC50 = 1 microM) of [3H]GABA release was dose-dependently blocked (IC50 = 0.1 microM for the stimulation caused by 10 microM L-DOPA) by the D1 antagonist SCH 23390, but was not affected by (-)-sulpiride, a D2 antagonist. SCH 23390 also blocked the stimulation in the other nuclei. The DOPA decarboxylase inhibitor NSD-1015 (500 microM) did not prevent the stimulation induced by L-DOPA in all of the studied nuclei. The results suggest that L-DOPA is able to activate D1 receptors located on the terminals of striatal projections via the dopamine formed by a decarboxylation mediated by an NSD-1015-resistant enzyme. Activation of the presynaptic D1 receptors results in stimulation of GABA release. PMID- 1902289 TI - Isoleucine397 is changed to threonine in two females with hemophilia B. PMID- 1902290 TI - The use of aztreonam in pediatric patients: a review. AB - Aztreonam is the first monobactam available for use in this country. A parenteral antibiotic, its antibacterial spectrum is limited to gram-negative aerobic pathogens. The drug's pharmacologic, pharmacokinetic, and toxicologic properties are reviewed. Based on early experience in pediatric patients, certain recommendations can be made for the use of aztreonam. PMID- 1902291 TI - Muromonab CD-3: a review of its pharmacology, pharmacokinetics, and clinical use in transplantation. AB - Muromonab CD-3 (OKT-3) is a monoclonal antibody that is highly effective in the treatment of acute rejection in solid organ transplants. Due to its monoclonal nature, each molecule is identical because it is derived from a single antibody producing clone. OKT-3 is administered only by intravenous injection and has a harmonic half-life of approximately 18 hours. It binds specifically to the CD-3 complex, which is involved in antigen recognition and cell stimulation, on the surface of T lymphocytes. Immediately after administration CD-3-positive T lymphocytes are abruptly removed from the circulation. The route of metabolism for OKT-3 is not clear; it may be removed by opsonization by the reticuloendothelial system when bound to T lymphocytes, or by human antimurine antibody production. The agent has been effective in reversing corticosteroid resistant acute rejection in renal, liver, and cardiac transplant recipients. Its use in pancreatic and bone marrow recipients is inconclusive. OKT-3 has a considerable number of initial side effects, and some life-threatening reactions may occur. This drug should not be administered to any patient who is greater than 3% usual body weight because of the potential for the development of severe pulmonary edema. OKT-3 may also be associated with a high rate of infection, especially of the viral type. The usual dose is 5 mg administered as an intravenous bolus over 2-4 minutes daily for 10-14 days. Approximately 85% of patients treated with OKT-3 develop reactive human antimurine antibodies that, over time, may lead to tachyphylaxis and neutralization of the murine antibody OKT-3. OKT-3 is potent immunosuppressive agent and is an important prototype of future monoclonal antibodies. PMID- 1902292 TI - Heterogeneity in plasminogen activator (PA) levels in human prostate cancer cell lines: increased PA activity correlates with biologically aggressive behavior. AB - Plasminogen activators (PA), particularly the lower Mr urokinase (u-PA) type, have been associated with tumor cell invasion and metastasis. We have examined the expression of PA by two human prostate cancer cell lines (PC-3 and DU-145) using functional and immunologic techniques. The culture media and cell extracts of the more aggressive PC-3 cell line contained more than two-fold greater PA activity than the relatively indolent DU-145 cell line. Zymographic studies identified the PA expressed as u-PA. PC-3 cells expressed an additional lower molecular weight form of u-PA not noted in DU-145 cells. Heterogeneity in u-PA expression was shown by the fibrin lysis assay, immunohistochemistry, and dual parameter flow cytometry indicating the presence of phenotypically divergent cell populations. Increased u-PA expression may identify those tumor cells that possess aggressive biological potential. PMID- 1902293 TI - The economics of health care. PMID- 1902294 TI - Temperature effects on serum prolactin concentrations and activity of dopaminergic neurons in the infundibulum/pituitary stalk of calves. AB - The effects of ambient temperature on serum concentrations of prolactin and neurochemical estimates of activity of dopaminergic neurons projecting to the infundibulum/pituitary stalk were investigated in Holstein bull calves. Accumulation of 3,4-dihydroxyphenylalanine (DOPA) in the infundibulum/pituitary stalk after intravenous injection of a decarboxylase inhibitor was used to estimate activity of these dopaminergic neurons. Increasing ambient temperature from 21 to 33 degrees C for 22 hr increased serum concentrations of prolactin and decreased activity of the dopaminergic neurons. Conversely, reducing ambient temperature from 22 degrees C to 11 degrees C decreased serum concentrations of prolactin and increased activity of these dopaminergic neurons. It is suggested that alterations in activity of dopaminergic neurons terminating in the infundibulum/pituitary stalk of bull calves may mediate acute temperature-induced changes in secretion of prolactin. PMID- 1902296 TI - Factors influencing the natural course of HDV hepatitis. PMID- 1902295 TI - Dietary magnesium depletion: p-nitroanisole metabolism and glucuronidation in rat hepatocytes and hepatic microsomal membranes. AB - Male Sprague-Dawley rats were pair fed either a control magnesium diet (480 mg/kg) or a magnesium-deficient diet (30 mg/kg) for 10 days to produce magnesium depletion. Serum magnesium concentration declined 60%, but tissue magnesium deficiency was not apparent. Hepatic parenchymal cells and microsomal membranes were isolated to evaluate in vitro metabolism of p-nitroanisole and conjugation of its metabolite, p-nitrophenol (pNP). O-Demethylation of p-nitroanisole was decreased slightly in both magnesium depletion hepatocytes and microsomal membranes. However, pNP glucuronide formation was specifically decreased 50% in the magnesium depletion cells at all p-nitroanisole concentrations. Similar results were found in the microsomal reaction system measuring pNP conjugation. Thus, early stages of magnesium depletion may result in a specific decrease in the pNP UDP-glucuronyl transferase activity. PMID- 1902297 TI - Hepatitis D virus and other chronic viral infections in high risk populations: interaction from an epidemiologic perspective. PMID- 1902299 TI - Effects of eicosapentaenoic acid and arachidonic acid on incorporation and metabolism of radioactive linoleic acid in cultured human fibroblasts. AB - Effects of exogenous eicosapentaenoic acid, arachidonic acid and oleic acid on incorporation and metabolism of [14C] linoleic acid were examined in cultured human fibroblasts obtained from three donors of different ages. Eicosapentaenoic acid treatment (40 microM) inhibited incorporation of radioactive linoleic acid and actively reduced radioactivity of desaturation-elongation metabolites in phospholipids, predominantly in the phosphatidylethanolamine fraction. In contrast, radioactivities of the metabolites in triacylglycerols were significantly increased with arachidonic acid treatment (40 microM): eicosapentaenoic acid had a smaller effect or none. Oleic acid had virtually no effect. These effects were consistent in the three cell lines, but responses to treatment with the acids differed considerably among individual cells. The pool of linoleic acid metabolites in triacylglycerols may not be negligible. The exogenous fatty acids may influence both the transfer of lipids between the major lipid pools as well as the activities of the desaturation-elongation system. PMID- 1902298 TI - Different changes of n-6 fatty acids in lipoproteins from hyperlipemic subjects after diets supplemented with n-3 fatty acids. AB - After diets supplemented with canned mackerel or herring, in a cross-over design, containing different amounts of long-chain n-3 fatty acids (eicosapentaenoic acid, C20:5n-3-EPA, and docosahexaenoic acid, C22(6)n-3-DHA) an increase of both EPA and DHA was confirmed in triglycerides (TG), cholesterol esters (CE) and phospholipids (PL) of very low density (VLDL) and low density lipoproteins (LDL) as well as in high density lipoproteins (HDL) from hyperlipidemic subjects. An unexpected finding was the simultaneous increase of arachidonic acid (C20:4n-6 AA) in TG and CE and its constant portion in PL of lipoproteins, whereas linoleic acid (C18:2n-6-LA) appeared lower in CE and in PL of VLDL + LDL and HDL. In general, the changes were minor after a diet supplemented with canned herring providing a lower dose of n-3 fatty acids. The results indicate dose-related changes not only of n-3 fatty acids, but also of n-6 fatty acids in serum lipids after fish diets. This different behavior of LA and AA in serum lipids might be a new aspect in the interrelations and the dietary modulation of both families of polyunsaturated fatty acids (PUFA). The accumulation of AA in neutral lipids could be linked with an elevation of prostaglandin I2, which was found apart from an increased formation of prostaglandin I3 after diets supplemented with n-3 fatty acids. The concomitant increase of prostaglandins I2 and I3 spotlights widely ignored interrelations within the eicosanoid pathway, which become evident after diets enriched with long-chain n-3 fatty acids. PMID- 1902300 TI - Ultrastructural localization of arachidonic acid in stimulated macrophages. AB - The distribution of 3[H] arachidonic acid incorporated into cultured mouse peritoneal macrophages was assessed upon stimulation of the cells with either the calcium ionophore A23187 or zymosan. After a labeling time of 24 h, cells were stimulated and processed for light and electron microscopic autoradiography. Grains were primarily localized over the plasma membrane and lipid-containing vesicles of both control and stimulated cells. In macrophages stimulated with ionophore, a decreased labeling density was evident in both of these cell compartments. Similar alterations in labeling pattern were observed in zymosan treated cells, although a larger decline in grain density occurred from the plasma membrane compartment. Immunocytochemical localization of PGE2, a major eicosanoid product released upon ionophore stimulation, revealed the presence of the prostaglandin in clear vesicular structures, many of which appear to be continuous with the plasma membrane. These results provide morphological evidence that different cellular pools of arachidonic acid may be differentially mobilized for eicosanoid production as a function of the mode of stimulation. PMID- 1902301 TI - A presidential health mission to Africa. PMID- 1902303 TI - AIDS awareness in North Dakota--a knowledge and attitude study of the general population. AB - The AIDS program of the North Dakota Department of Health and Consolidated Laboratories has provided a broad range of information concerning AIDS (acquired immunodeficiency syndrome) and HIV (human immunodeficiency virus) to State residents over the past few years. The ultimate intent of these intervention efforts was to decrease viral transmission. To assess residents' knowledge and attitudes regarding AIDS, a statewide, random telephone study was conducted by AIDS Program personnel in the fall of 1987, 1988, and 1989, with technical assistance from the Bureau of Governmental Affairs, University of North Dakota. Study results indicated a majority of the respondents considered themselves to have at least "some" knowledge about AIDS. Participants' comprehension of viral transmission routes and prevention methods increased over the 3 years, yet misconceptions still exist. Identified areas of misconception were accentuated in subsequent State educational programs. When the results were compared with national studies, knowledge levels in North Dakota were generally similar to but frequently superior to the nationwide levels. PMID- 1902302 TI - AIDS knowledge in low-income and minority populations. AB - A convenience sample of 587 subjects was selected from the waiting areas of community health centers in Harris County, TX. They completed a structured interview that included questions on their knowledge of acquired immunodeficiency syndrome (AIDS) transmission and prevention. Hispanic patients were interviewed in their preferred language. They were given a cumulative correct score for 10 questions on AIDS. An ANOVA showed significant differences in knowledge between each radial group. Cumulative scores were whites, 78 percent correct; blacks, 68 percent correct; and Hispanics, 61 percent correct. Only 58 percent of Hispanics reported that using a condom during sexual intercourse lowered the risk of contracting AIDS, compared with 84 percent of whites and 83 percent of blacks. A regression analysis showed significant effects for both education and racial group, but not for age and sex. These findings show that knowledge of AIDS can be predicted according to the race and education of the population using these community health centers. Additional attention should be focused on educating low income blacks and Hispanics about AIDS. PMID- 1902304 TI - Black-white differences in alcohol use by women: Baltimore survey findings. AB - Although black women suffer disproportionately from alcohol-related illnesses and causes of death, little is known about the extent to which poorer outcomes are a function of differences in drinking, the use of health services, or some combination of these factors. This study, using interview data obtained in the Baltimore Epidemiologic Catchment Area household survey, compares racial differences in alcohol use and abuse among a sample of 2,100 women. After controlling for differences in sociodemographic characteristics, black women were found to be at no greater risk than whites for heavy drinking or for suffering from alcohol abuse or dependence. Racial differences, however, were observed in heavy drinking by years of education. A similar percentage of black women and white women who had not completed high school were heavy drinkers, but black women with 12 or more years of education were less likely to be heavy drinkers than whites with comparable education. These findings raise questions about the extent to which differences in drinking contribute to the poorer alcohol-related health outcomes of black women in Baltimore. Additionally, the finding that education was inversely related to heavy drinking among black women may be helpful in shaping early alcohol abuse intervention and treatment services that target black women. PMID- 1902305 TI - Strategic planning for public health practice using macroenvironmental analysis. AB - Macroenvironmental analysis is the initial stage in comprehensive strategic planning. The authors examine the benefits of this type of analysis when applied to public health organizations and present a series of questions that should be answered prior to committing resources to scanning, monitoring, forecasting, and assessing components of the macroenvironment. Using illustrations from the public and private sectors, each question is examined with reference to specific challenges facing public health. Benefits are derived both from the process and the outcome of macroenvironmental analysis. Not only are data acquired that assist public health professionals to make decisions, but the analytical process required assures a better understanding of potential external threats and opportunities as well as an organization's strengths and weaknesses. Although differences exist among private and public as well as profit and not-for-profit organizations, macroenvironmental analysis is seen as more essential to the public and not-for-profit sectors than the private and profit sectors. This conclusion results from the extreme dependency of those areas on external environmental forces that cannot be significantly influenced or controlled by public health decision makers. PMID- 1902306 TI - Evaluation and implementation of public health registries. AB - A rapid proliferation of registries has occurred during the last 20 years. Given the long-term commitment of resources associated with registries and limited public health funding, proposals for new registries should be carefully considered before being funded. A registry is defined as a data base of identifiable persons containing a clearly defined set of health and demographic data collected for a specific public health purpose. Criteria for evaluating whether a registry is needed, feasible, or the most effective and efficient means of collecting a specific set of health data are presented. They include an evaluation of the stated purpose; a review of the function, duration, and scope of the registry; consideration of existing alternative data sources; an assessment of the practical feasibility of the registry; the likelihood of sufficient start-up and long-term funding; and an evaluation of the cost effectiveness of the registry. Creating a public health registry is a complex process. A range of technical and organizational skills is required for a registry to be successfully implemented. Eight requirements are identified as crucial for the successful development of a new registry. They include an implementation plan, adequate documentation, quality control procedures, case definition and case-finding (ascertainment) procedures, determination of data elements, data collection and processing procedures, data access policy, and a framework for dissemination of registry data and findings. PMID- 1902307 TI - Survey of state public health departments on procedures for reporting elder abuse. AB - All 50 States have passed legislation to protect elderly victims of domestic abuse and neglect. Forty-two States have mandatory reporting laws, with health care providers considered the major professional referral service. This exploratory study of State health departments had as its goals (a) the identification of administrative awareness regarding the State law, (b) the perception of difficulties encountered in the reporting process, and (c) the development of procedures, such as written materials or training curriculum, to assist health personnel with the reporting responsibilities. The study was carried out between April and October 1989. A brief questionnaire was mailed to State health department directors. All 50 States responded, although the respondents represented varying disciplines and staff responsibilities within the health departments or were from agencies that the State had designated to investigate elder abuse. These data should be considered preliminary and suggestive of service needs. The results demonstrated an inverse relationship between awareness of the laws or regulations and specific activities to support the reporting process. Ninety-four percent of respondents were aware of the State law, but only 20 to 28 percent reported the use of written procedures or training materials specifically designed for health personnel. At the same time, approximately one-third were aware of reporting issues that needed to be addressed, including staff unfamiliarity with the regulations, concerns of confidentiality, and uneasiness about reporting in general. Part of the reason for what appears to be inactivity on the part of the State departments of health may lie in the fact that elder abuse reporting laws tend to place implementing authority with human service, aging, or law enforcement agencies rather than with health departments. The variability in reporting and investigative regulations among State elder abuse laws suggests that one national written training program or awareness campaign would be inappropriate. Individual State differences must be recognized for planning and implementation. State health departments,familiar with the law and concerned about the welfare of vulnerable populations, are critically situated to contribute to a strong protective service environment. A major responsibility is to ensure that health care providers are aware of elder abuse as a problem, know its signs, and can effectively carry out reporting obligations. Health departments can be useful facilitators in the development of interdepartmental coordination to address the complex issues of elder abuse. PMID- 1902309 TI - Prevalence of elevated serum cholesterol in personnel of the U.S. Navy. AB - Fasting blood lipid profiles were collected for 5,487 active duty Navy men and women presenting for routine physical examinations. Mean serum cholesterol for the sample (mean age 33.6 years) was 208.2 milligrams per deciliter (mg per dL). Cholesterol level increased with age, decreased with education, and was higher in men than in women. Using the Navy's own risk cutpoints for total cholesterol (200 mg per dL for ages 18-24, 220 mg per dL for ages 25 and older), 36.9 percent of the sample were found to be at risk. When the percentage of the population at risk was computed using the guidelines suggested by the National Institutes of Health Consensus Conference, rather than the Navy's cutpoints, results were almost identical (36.3 percent at risk); when based on the National Cholesterol Education Program's recommended cutpoints, the percent at risk was considerably higher (55.4 percent). Risk estimates that included LDL- or HDL-cholesterol risk levels (or both) also were higher. A larger percentage of Navy personnel were at risk because of total cholesterol than were persons in an age-adjusted national sample. However, because routine examinations generally are not given until first reenlistment, the Navy sample underrepresented younger service members, and results may overestimate the prevalence of hypercholesterolemia in the Navy at large. The author draws attention to the problem of lack of standardization in cholesterol testing and notes that the Navy does not yet participate in an external quality control program. The difficulty in setting appropriate risk cutpoints, given the complexity of factors that must be considered as well as the general unreliability of cholesterol tests, is also discussed. PMID- 1902308 TI - Nurses' knowledge, attitudes, and beliefs regarding organ and tissue donation and transplantation. AB - The acute shortage of human organs and tissues for transplantation has been attributed in part to health professionals, including nurses, for their reluctance to recognize and refer suitable candidates for donation. In 1988, nurses' knowledge, attitudes, and beliefs regarding organ and tissue donation and transplantation were assessed using a 70-item questionnaire. Respondents included 1,683 nurses employed in 62 rural and urban hospitals in the Midwest. Only 365 respondents (21.7 percent) reported having requested tissue donations and 243 (14.4 percent) reported having requested organ donations. However, of those who requested tissue or organ donations, 270 (74 percent) obtained consents for tissues and 150 (61.7 percent) obtained consent for organ donations. Respondents were knowledgeable about organ and tissue donation (mean score of 7.5 on a 0 to 10 knowledge scale with 10 as highest) and reported attitudes and beliefs were moderately positive. Factors that were significantly correlated with the number of requests made for organs and tissues and the number of consents obtained included nurses' knowledge, attitudes, and beliefs about donation; nurses' perception of their own confidence in their ability to request tissues and organs; being a supervisor; and working in an emergency department. PMID- 1902310 TI - Using linked program and birth records to evaluate coverage and targeting in Tennessee's WIC program. AB - Public health nutrition programs are intended to serve low-income families who are at greater nutritional risk than the general population. Not all persons who are program-eligible are at equal risk, however. It would be desirable to evaluate a program's ability to enroll persons from higher risk backgrounds in the population (coverage) and, conversely, the extent to which those enrolled in this program are at higher risk (targeting). A method for the evaluation of coverage and targeting was developed using data from the Tennessee Women, Infants, and Children Special Supplemental Food Program (WIC) linked with birth certificates. The linked computer file was created by matching the name and date of birth in both record files. The birth records were the common source of information used to characterize the risk background for both the WIC and non-WIC participants. Maternal sociodemographic information on the birth records was used to define the health risk background of each child. The coverage and targeting of "at-risk" children were computed and compared for 50 counties or county aggregates in Tennessee. Considerable variation in the coverage and targeting rates of at-risk children was observed among Tennessee counties, although the counties within each WIC administrative region tended to have similar coverage and targeting patterns. Using the existing data in linked program and vital records provides a direct evaluation of a program. Coverage and targeting evaluation can be used to detect underserved populations within small geographic areas. PMID- 1902311 TI - Adults' accounts of onset of regular smoking: influences of school, work, and other settings. AB - A representative population sample of 546 adults in Victoria, Australia, who had ever smoked were asked to describe the general setting where they first took up regular smoking and who, if anyone, influenced them to begin. Although school was the dominant setting (35 percent), particularly for younger respondents 20-34 years (55 percent), the workplace was also an important setting for uptake of regular smoking. Overall, 34 percent reported taking up smoking while in a job. The probability of taking up smoking at work increased with age but, even among younger respondents, many did not begin smoking until they started work. Fourteen percent took it up between leaving school and commencing college or a university or their first job, and 22 percent of those who attended college or a university took up smoking in that setting. One-quarter of the sample said that nobody had influenced them to take up smoking, but most of the remainder indicated that either friends, family, or workmates had played a part. Most mentioned were good friends at school (20 percent), good friends known socially (14 percent), and good friends at work (7 percent). Others listed were family (7 percent), boy friend or girl friend (7 percent). Overall, 10 percent had taken up regular smoking under the influence of workmates at work, suggesting that smoke-free workplace policies might be useful in the long term in reducing the prevalence of smoking in the community. PMID- 1902313 TI - A community home inspection approach to preventing falls among the elderly. AB - Falls are the leading cause of accidents among those ages 65 and older and the largest single cause of death due to injury of the elderly. Environmental factors play a key role in the probability of a fall in the homes of the elderly. A community health promotion team approach can reduce the prevalence rate of injuries due to falls by eliminating the risk factors precipitating the injuries. A comprehensive program in Wilmington, OH, will incorporate the use of the community senior citizens' center, the local college, fire department, local radio stations and newspapers, community churches, local merchants, educators, and the medical community. Extrinsic factors that previously have been linked directly to falls will be identified in the home inspections. The "Fixer-Up Team," composed of college students and community volunteers, will rectify any unsafe conditions found by the inspection team. Local merchants and lumber yards will donate materials to make needed repairs. Active senior citizens will be trained as part of the inspection team, allowing this program to be self perpetuating. Compared with the national prevalence rates, this program will show a decrease in injuries caused by falls in the homes of the participants of this program. PMID- 1902314 TI - A proposal for strengthening medical school training in STD prevention techniques. AB - Despite increases in national rates of sexually transmitted disease (STD), surveys indicate that medical students generally lack programs to train them in STD prevention techniques and in counseling patients about STD. The authors of this proposal investigated STD education for medical students at the University of California at Los Angeles and propose a project to involve third-year medical students in STD prevention techniques during their STD-clinic rotation. The long term goal is to decrease the incidence and prevalence of STD. The immediate aims are to increase medical students' knowledge of STD prevention and to help them develop the communication skills necessary to effectively counsel patients about STD. Interventions would consist of a series of lectures and workshops using audiovisual aids, small group discussions, and role playing, and would be conducted by health educators and guest lecturers. A quasi-experimental research design would be used in testing the effectiveness of the project in two experimental and two control groups involving a total of 80 third-year medical students. The first intervention would be a 1-week lecture series. Written tests would be given before and after the first intervention to measure the baseline of the students' knowledge of STD prevention methods. The second intervention would be a 1-week workshop series. Students' interviews with patients would be videotaped before and after the second intervention so that the interviewer's communication skills may be assessed and compared. Sets of interventions would be scheduled for the fall of 1990 and the spring of 1991. Six months after the completion of the project, a followup questionnaire would be given to evaluate the project's overall effectiveness. PMID- 1902312 TI - Boston's Codman Square Community Partnership for Health Promotion. AB - The Codman Square Community Partnership for Health Promotion is a program designed to promote changes in individual behavior and community relationships to reduce the morbidity and mortality associated with the many problems affecting poor, minority communities in the United States. Problems of particular concern to be addressed by the program include violence, injuries, substance abuse, acquired immunodeficiency syndrome (AIDS), infant mortality, child abuse and neglect, and cardiovascular disease. The failure of traditional health promotion approaches to poor communities has created a literature supporting community based action directed at broad social forces. The Codman Square Community Partnership for Health Promotion uses a variety of models--community participation, community organization, empowerment education, and community oriented primary care--to encourage new coalitions that can ameliorate the social isolation and health-averse social norms linked to poverty and poor health. The program uses local residents trained as lay health workers to deliver home-based health services and to help create the necessary partnerships, linkages, and communication networks to foster the reorganization of the community to better address its health problems. PMID- 1902315 TI - AIDS among women to double by 2000. PMID- 1902316 TI - Opportunistic infection drug research funds approved by NIAID. PMID- 1902317 TI - FDA standardizes testing of AIDS workers' gloves. PMID- 1902319 TI - Myelopathy following hyperfractionated accelerated radiotherapy for anaplastic thyroid carcinoma. AB - From 1975 to 1982, 32 patients with a diagnosis of anaplastic carcinoma of the thyroid were entered into a protocol of hyperfractionated accelerated radiotherapy. The tumor dose was 30-45 Gy at 1 Gy per fraction given 4 times a day at 3-h intervals. The results were disappointing with a median survival of less than 6 months. Two patients developed radiation myelopathy at 8 and 13 months, total spinal cord dose being 39.9 and 48.3 Gy, respectively. The risk of spinal cord damage was much higher than expected. The possible radiobiological causes and clinical implications are discussed. PMID- 1902318 TI - Accelerated treatment and radiation myelitis. PMID- 1902320 TI - Radiosensitization with normobaric oxygen and carbogen. PMID- 1902321 TI - Review of laboratory findings for patients with chronic fatigue syndrome. AB - Various abnormalities revealed by laboratory studies have been reported in adults with chronic fatigue syndrome. Those most consistently reported include depressed natural killer cell function and reduced numbers of natural killer cells; low levels of circulating immune complexes; low levels of several autoantibodies, particularly antinuclear antibodies and antithyroid antibodies; altered levels of immunoglobulins; abnormalities in number and function of lymphocytes; and modestly elevated levels of two Epstein-Barr virus-related antibodies, immunoglobulin G to viral capsid antigen and to early antigen. PMID- 1902322 TI - Controlling urban air pollution: a benefit-cost assessment. AB - To help focus debate about the best use of society's resources, it is important to have estimates of the benefits and costs of further improvements in air quality. Such estimates are developed, with focus primarily on reductions in ground-level ozone resulting from the control of volatile organic compounds; to a lesser extent, particulate control also is considered. Proposed controls are evaluated for both the nation as a whole and for the Los Angeles metropolitan area, where violations of air quality standards are most frequent and severe. Subject to a number of uncertainties, the costs of proposed new controls are found to exceed the benefits, perhaps by a considerable margin. PMID- 1902323 TI - Regulation of Ras-GAP and the neurofibromatosis-1 gene product by eicosanoids. AB - Ras-GAP (GTPase activating protein) is a regulatory protein that stimulates the intrinsic guanosine triphosphatase (GTPase) activity of the proto-oncogene product p21ras. A domain of the neurofibromatosis gene product (NF1) that has sequence similarity to the catalytic domain of Ras-GAP and to yeast IRA gene products also has a specific stimulatory activity toward p21ras GTPase. Arachidonic acid and phosphatidic acid inactivate GAP, but no agents have been identified that stimulate GAP and thereby switch p21ras off. With the use of recombinant Ha-c-Ras and Ras-GAP, NF1, and GAP catalytic domains, it was found that prostaglandins PGF2 alpha and PGA2 stimulated Ras-GAP and that prostacyclin PGI2 inhibited Ras-GAP. The stimulatory effect of PGF2 alpha was saturable and structure-specific and competed with the inhibitory effect of arachidonic acid. Arachidonic acid also inhibited the catalytic activity of NF1, but prostaglandins were not stimulatory. These results suggest a mechanism for the allosteric control of Ras function through the modulation of arachidonate metabolism. PMID- 1902324 TI - Bone island (enostosis): clinical significance and radiologic and pathologic correlations. AB - This study was undertaken to explain the increased scintigraphic activity of some bone islands by correlating the clinical, radiographic, scintigraphic, and histopathologic findings. The material for the study consisted of six patients with bone islands who had undergone histopathologic examinations of the lesions. Based on histopathologic-radiologic correlations, we postulate that the osteoblastic activity of a bone island makes it appear "hot" on scintigraphy, although other factors such as the size of the lesion may play some role in this phenomenon. In addition, we tried to find a logical algorithm for the radiologic evaluation and management of sclerotic lesions that look like bone islands but exhibit increased uptake of radiopharmaceuticals on bone scan examination. We emphasize that the morphology of the lesion, as demonstrated on the radiologic examination, rather than its degree of activity on the bone scan is a guide to the correct diagnosis. PMID- 1902325 TI - Total parenteral nutrition and tumor metastasis. AB - A major clinical concern with providing total parenteral nutrition to the tumor bearing host is the potential to stimulate tumor growth. This study was performed to determine the effect of total parenteral nutrition on primary tumor growth and spontaneous pulmonary metastasis in Lobund rats with subcutaneous prostate adenocarcinoma (PA-III) implants. Significant acceleration of primary tumor growth and tumor metastasis occurred in animals receiving parenteral nutrition consisting of amino acids, dextrose, and lipid or standard enteral nutrition compared to control animals. This study represents the first report of stimulating tumor metastasis with specific parenteral nutrients and clearly indicates that both primary tumor growth and tumor metastasis can be altered by exogenous substrate administration. PMID- 1902326 TI - ES in patients with periampullary diverticula and gallbladder in situ. PMID- 1902328 TI - Nitroprusside in vitro inhibits platelet aggregation and intracellular calcium translocation. Effect of haemoglobin. AB - The biologically final active compound of nitrovasodilators is now supposed to be nitric oxide (NO), a labile substance identical to EDRF. The effects of nitroprusside on platelet functions were studied in vitro. Platelet aggregation induced by several stimuli (ADP, collagen, arachidonic acid and PAF) was inhibited by increasing concentrations of the drug (1-50 uM); interestingly, the potency of nitroprusside is higher when PAF is employed as stimulating agent in comparison with the other agonists (ED50 = 2 uM for ADP, 2.5 uM for A.A., 4.5 uM for collagen and 0.3 uM for PAF-induced aggregations). The concomitant addition of haemoglobin is able to reverse the inhibitory effect of nitroprusside, according to the view that haemoglobin possesses a high affinity for NO, thus antagonizing the effect of this compound. Nitroprusside was also able to inhibit intracellular calcium translocation, as studied with the Quin 2 technique, induced by PAF and arachidonic acid. Fron these observations the hypothesis may be suggested that nitroprusside inhibits platelet functions by mimicking the endogenous NO, and that the intracellular calcium metabolism is involved in the inhibitory activity of the drug. PMID- 1902327 TI - Sustained enhancement of gastric HCO3 secretion in humans by enprostil. AB - Twelve healthy, male volunteers were treated for ten days, in double-blind conditions, with either enprostil, a PGE2 derivative, at a dose of 35 micrograms bid or with placebo. Before and after treatment fasting gastric juice was collected and basal bicarbonate secretion was measured by Feldman's method. In the enprostil group a statistically significant (p less than 0.01) increase in gastric HCO3 output was detectable 12 hours after the last dose. That finding, which is in keeping with the results of acute single-dose studies, suggests that stimulation of bicarbonate secretion by enprostil is not merely a transient phenomenon involved in the prevention of mucosal injury, but a lasting effect that may contribute to the ulcer-healing activity of the drug. PMID- 1902329 TI - Effective induction of anti-phospholipid and anticoagulant antibodies in normal mouse. AB - Anti-phosphatidylserine (anti-PS) antibodies of the IgG isotype in the serum of BALB/c mouse were effectively induced by the intrasplenic immunization of phosphatidylserine (PS), while only a slight increase of the titer was observed when the antigen was injected intravenously. The serum antibodies cross-reacted extensively with other acidic phospholipids, but not with phosphatidylcholine (PC). A remarkable frequency of anti-PS mAbs of the IgG isotype was also observed even when mAbs were produced 10 days after the intrasplenic injection of the antigen. Reactivities of the fifteen mAbs, which had been established from BALB/c mice by the intrasplenic immunization with PS, were further analyzed. Among the fifteen mAbs examined, thirteen cross-reacted with ssDNA and two bound to dsDNA. Seven mAbs had lupus anticoagulant activity and four bound to cultured human umbilical vein endothelial cells (HUVECs). No significant correlation was found among phospholipid specificities, anti-DNA, anticoagulant, and HUVEC binding activities. One mAb of the IgG2b subclass, named PSG3, which had been produced 10 days after the immunization, was shown to have a strong lupus anticoagulant, dsDNA binding, and HUVEC binding activities. PMID- 1902330 TI - Heparin binds normally to platelets digested with Streptomyces griseus protease. PMID- 1902332 TI - [Asymptomatic genital infection by Chlamydia trachomatis in women. A cost analysis of control check-ups]. AB - Asymptomatic genital infection by Chlamydia trachomatis is common in women, and one or more consultations to test for cure is the routine practice. We have compared the economic implications of two post-treatment regimens: 1) no control, and 2) one control involving a single test for C trachomatis, with renewed treatment and another test for cure in women who were chlamydia-positive, etc. The costs of the control regimen were double those of the no-control regimen. With no control, 79 more cases of pelvic inflammatory disease, eight more cases of infertility requiring work-up and two more cases of ectopic pregnancy would occur per 10,000 patients. We conclude that routine post-treatment control of asymptomatic genital chlamydial infections is not cost beneficial. PMID- 1902331 TI - [Hepatitis A-, B- and C-markers among Norwegian drug addicts in the period 1975 89]. AB - The prevalence of hepatitis A-, B- and C-markers has been studied in patients at a Norwegian rehabilitation centre for drug addicts. The prevalence of hepatitis C antibodies was fairly constant in the years 1976 (56%), 1985 (78%) and 1988-89 (73%), but may be decreasing in younger addicts. The data suggest a highly variable incidence of HAV with few infections in recent years. The prevalence of hepatitis B-markers, which has been calculated from 1975 to 1988-89, reached a maximum of 93% in 1986. Since then a significant decrease in prevalence has been observed among younger patients, suggesting that the HIV campaign has led to improved hygiene precautions among intravenous drug addicts. A strong correlation was observed between positive markers for HBV and presence of anti-HCV, and, similarly, between the presence of anti-HAV and markers for HBV and HCV. Anti-HCV was significantly associated with pathological ALT-values. PMID- 1902333 TI - Xylazine-induced pulmonary edema in rats. AB - Inhibitors of cytochrome P450, such as SK&F 525-A, prolong the duration of xylazine-ketamine anesthesia and cause pulmonary edema (PE) and death in rats. To determine the cause of PE, Sprague-Dawley rats were given a single dose of xylazine (21 mg/kg, im) alone or in combination with ketamine (45 mg/kg, im) and/or SK&F 525-A (50 mg/kg, ip) and percentage lung to body weight (%LW/BW) ratios (as an indicator of PE) were compared. The results indicated that xylazine caused PE which was independent of ketamine and was enhanced by SK&F 525-A. Subsequently, it was determined that 42 mg/kg xylazine, im, is an optimal edemagenic dose. Xylazine (42 mg/kg, im) increased the %LW/BW ratio as compared to control. Pleural effusion (PLE) of various amounts was observed in 75% of the animals. The pleural fluid to serum protein ratio for xylazine was similar to that obtained for alpha-naphthylthiourea (5 mg/kg, ip). Extensive serous PLE and alveolar edema with hemorrhage were found at necropsy in xylazine-treated rats. Pretreatment with yohimbine (4.2 mg/kg), prazosin (20 mg/kg), tolazoline (20 mg/kg), yohimbine (4.2 mg/kg) plus prazosin (20 mg/kg), atropine (20 mg/kg), dimethyl sulfoxide (DMSO) (7.8 g/kg), allopurinol (50 mg/kg), superoxide dismutase (20,000 U/kg), catalase (20,000 U/kg), BW755C (50 mg/kg), ibuprofen (50 mg/kg), cystathionine (100 mg/kg) plus taurine (100 mg/kg) did not affect the %LW/BW ratio. PLE was increased by yohimbine, yohimbine plus prazosin, and allopurinol, reduced by DMSO, and not changed in other groups. The results indicate that xylazine caused increased-permeability PE characterized by rapid onset, cellular damage and protein-rich pleural fluid. PE may not be mediated by adverse cardiovascular effects of xylazine and oxygen radicals are possibly involved in its etiology. PMID- 1902334 TI - Bioactivation of aflatoxin B1 by human liver microsomes: role of cytochrome P450 IIIA enzymes. AB - Based on our previous observations (H. S. Ramsdell and D. L. Eaton, 1990, Cancer Res. 50, 615-620) that the proportion of aflatoxin B1 (AFB1) converted to the highly reactive AFB1-8,9-epoxide in microsomal incubations varies with substrate concentration, we have examined the hypothesis of T. Shimada and F. P. Guengerich (1989, Proc. Natl. Acad. Sci. USA 86, 462-465) that cytochrome P450 IIIA4 is principally responsible for the activation (epoxidation) of AFB1 by human liver microsomes. The initial rates of formation of AFB1-8,9-epoxide and hydroxylated AFB1 metabolites were determined in microsomes prepared from livers of organ donors (n = 14) at AFB1 concentrations of 124 and 16 microM. Microsomal oxidation of nifedipine, catalyzed primarily by P450 IIIA enzymes, was also determined by HPLC. Rates of formation of AFB1 metabolites and nifedipine oxidation were poorly correlated at either AFB1 concentration (r2 = 0.13-0.41). A somewhat better correlation between AFB1 epoxidation and nifedipine oxidation was observed at 124 microM AFB1 (r2 = 0.41) than at 16 microM AFB1 (r2 = 0.26). Treatment of pooled microsomes with troleandomycin, an apparently specific inhibitor of P450 IIIA enzymes, resulted in 35% inhibition of AFB1-8,9-epoxide formation at the high AFB1 level but had little effect at 16 microM AFB1. An antibody against rat cytochrome P450 IIIA1 significantly inhibited AFB1 epoxidation at high, but not low, AFB1 concentrations, whereas AFQ1 formation was strongly inhibited at all substrate levels examined. These results are consistent with the hypothesis that cytochrome P450 IIIA enzyme(s) can form AFB1-8,9-epoxide, but are effective at only relatively high substrate concentrations. Another P450 enzyme(s) appears to be principally responsible for AFB1-8,9-epoxide formation at the low AFB1 levels that would be typical for dietary exposures. PMID- 1902335 TI - Functional changes of the biliary tree associated with experimentally induced cholestasis: sulfobromophthalein on manganese-bilirubin combinations. AB - Administration of combinations of manganese (Mn) and bilirubin (BR) to rats results in a severe, but reversible diminution of bile flow, an effect that can be abolished if sulfobromophthalein (BSP) is given at a specific time prior to BR. Some studies suggest that changes in the bile canalicular membrane (BCM) are critical to the response. One aim of the present work was to determine if functional changes in BCM also become more marked with increasing doses of BR. A second aim was to investigate the protective effects of BSP on MnBR-altered biliary function. The permeability of the biliary tree was evaluated by the segmented retrograde intrabiliary injection (SRII) procedure in male Sprague Dawley rats treated with varying combinations and dosages of Mn, BR, and BSP. [3H]Mannitol and [3H]inulin were used as marker substances of the biliary tree (canalicular membrane and tight junctions, respectively). Administration of Mn, followed 15 min later by BR, led to a reduction in bile flow that was dose dependent on BR. The percentage recovery of both inulin and mannitol in bile after SRII also decreased significantly with increasing dosages of BR. When BSP was given 10 min before BR, MnBR-induced reduction in bile flow was abolished. BSP treatment also prevented MnBR-induced reduction in biliary recovery of both inulin and mannitol after SRII; this was more evident with mannitol than with inulin. BSP protection against MnBR cholestasis depends upon when it is administered relative to BR injection. The relationship of BSP relative to BR injection was comparable for both reduced bile flow and the recoveries of marker substances in bile after SRII. The data are consistent with the conclusion that changes in biliary tree permeability, particularly at the canalicular membrane, likely lead to MnBR-induced cholestasis. PMID- 1902336 TI - An empirical evaluation of the performance of antibody identification tasks. AB - Four empirical studies were conducted for better understanding of the nature of problem-solving activities by medical technologists and medical technology students when performing antibody identification tasks. The results indicated the importance of strategies that ensure the collection of converging evidence, as these strategies protect against the fallibility of commonly used heuristics and against errors due to simple slips. The results also indicate that not only do students make significant numbers of errors, but so do practicing technologists. In one of the studies covering a 1-year period, for instance, a group of 16 technologists made a total of 41 errors in 1057 cases. On the basis of these findings, several alternatives are proposed to reduce errors. PMID- 1902337 TI - Transfusion practice in central Virginia. AB - Increasing concern about the safety of transfusions and a desire to balance blood supply and blood needs stimulated a regional blood center to study the utilization of blood, rather than simply looking at distribution. A comprehensive survey of transfusion use, including packed red cells (RBCs), fresh-frozen plasma (FFP), and platelets (PLTs), was conducted in 12 Central Virginia hospitals. The medical records of 2579 transfused patients showed that the principal diagnoses in 23 percent of patients involved diseases of the circulatory system and those in 16 percent involved neoplasms, as classified under the diagnosis-related groups. Sixty-six percent (n = 1691) of patients had some type of surgery, with surgical patients overall using 1.9 times as many units of blood (RBCs, FFP, and PLTs) as nonsurgical patients. Mean patient age was 61 years, and the male:female ratio was 48:52 percent. This descriptive analysis of regional blood utilization has facilitated planning for local blood needs, provided indicators for areas of largest blood use, and given this region and others baseline data for future comparison. PMID- 1902338 TI - A cryoglobulin with cold agglutinin and erythroid stem cell suppressant properties. AB - A 93-year-old woman presented with profound anemia (hematocrit 23% [0.23]); there was clumping of her red cells in test tubes and on peripheral blood smears. There was also a marked decrease in erythroid precursors in the bone marrow and reticulocytopenia in the peripheral blood. An IgM kappa monoclonal gammopathy was found in low concentration (approximately 1%) in her serum, and the cold agglutinins had a titer of 2560. However, the cold agglutinin titer of the supernatant after cryoglobulin precipitation was 40. Redissolving the cryoglobulin in the supernatant resulted in a cold agglutinin titer of 1280. Moreover, the addition of the patient's whole serum inhibited erythroid colony formation in culture. The inhibition was removed by cryoprecipitation of the cryoglobulin. The patient was given steroid therapy, to which she responded with reticulocytosis and an elevation of hematocrit. By 3 months, the cold agglutinin titer had fallen to 10. She remained well 4 years later. Whereas reports of cryoprecipitable cold agglutinins are rare, this case is unique because there have been no previous reports that these cold active proteins also have erythroid stem cell-suppressant properties. PMID- 1902339 TI - Rh hemolytic disease of the newborn treated with high-dose intravenous immunoglobulin and plasmapheresis. PMID- 1902340 TI - Effects of CO2 and N2 partial pressures on cognitive and psychomotor performance. AB - This study examined N2 and CO2 components of narcosis by comparing the effects of three levels of PETCO2 [low = 29 mmHg (SD = 4 mmHg), medium = 47 mmHg (SD = 1 mmHg), high = 57 mmHg (SD = 2 mmHg)] at 1 and 6 atm abs in 12 male volunteers. Cognitive and psychomotor performances were examined using a variety of tasks, including a modified Stroop test, an arithmetic test, number comparison, a figure copying test, and the Purdue pegboard test. Performance on all tasks demonstrated significant (P less than 0.05) decrements at 6 atm abs. High CO2 tensions significantly impaired cognitive and psychomotor performance at 1 atm abs and caused further decrements at 6 atm abs (P less than 0.05). However, no significant N2-CO2 interaction (P greater than 0.05) or global threshold for the onset of CO2 narcosis was indicated by the test scores. The pattern of intratest results were different for N2 and CO2. At high PETCO2, performance deficits were due to a slowing of performance rather than a disruption of the accuracy of processing. Nitrogen narcosis, conversely, produced significant impairment through both decreases in the speed and accuracy of processing on the majority of performance tests. It was concluded that within the PETCO2 ranges studied: a) PETCO2 and PIN2 are additive in their effects on impaired cognitive and psychomotor performance at depth; b) high PETCO2 and PIN2 induce distinctly different strategic responses on the speed accuracy trade-off function of the performance tests; c) decrements in cognitive and psychomotor performance under high PETCO2 do not conform to the predicted narcotic potency of CO2 according to the lipid solubility theory of narcosis. PMID- 1902341 TI - Analysis of the reactivity of anti-bovine CD8 monoclonal antibodies with cloned T cell lines and mouse L-cells transfected with bovine CD8. AB - Mouse L-cells transfected with bovine CD8 and two Theileria parva-infected cloned T cell lines expressing bovine CD8 were used to screen the panel of ten monoclonal antibodies (mAbs) submitted to the workshop. Eight of the ten mAbs reacted with the transfectant and both the cloned T cell lines. However, two mAbs CC58 and BAT82A did not recognise the transfectant and only reacted with one of the T cell lines. Further biochemical studies indicated that the eight mAbs react with both homo- and heterodimeric forms of bovine CD8 whilst the two mAbs CC58 and BAT82A react with only heterodimeric forms. These data suggest that bovine DC8 is encoded by two genes as is the case in mouse and man. PMID- 1902343 TI - Leukocyte antigens in cattle, sheep and goats. Monoclonal antibodies submitted for inclusion in the panel. PMID- 1902342 TI - Summary of workshop findings for leukocyte antigens of cattle. PMID- 1902344 TI - [The importance of blood gas analysis and acid-base equilibrium in pulmonary embolism]. AB - The authors examined in 60 patients with acute pulmonary embolism values of blood gases and acid-base equilibrium, incl. 30 from arterialized capillary blood, in another 30 subjects from arterial blood. On analysis of capillary blood hypoxaemia was present in all subjects, on analysis of arterial blood only in 63%. Respiratory alkalosis was found on capillary examination in 37%, on arterial examination in 23% of the patients. Hypoxaemia and hypocapnia thus are not specific phenomena in acute pulmonary embolism, in particular when accurate blood collection for analysis is respected, and normal values of paO2 and paCO2 do not rule out the presence of pulmonary embolism. In the development of hypoxaemia in patients with pulmonary embolism participates above all an incomplete right-to left pulmonary shunt, as revealed during calculation of the magnitude of the shunt by means of the so-called oxygen method in 30 patients with embolism, as compared with a group of 10 healthy subjects. PMID- 1902345 TI - 1990 McCollum Award lecture. Nutrition and immunity: lessons from the past and new insights into the future. PMID- 1902346 TI - Comparison of extracellular and net glucose oxidation measured isotopically and by indirect calorimetry during high and low glucose turnover. AB - To determine the extent to which glucose oxidation measured by indirect calorimetry reflects glucose oxidation measured isotopically, subjects were studied during a 6-h hyperinsulinemic euglycemic clamp (1 mU.kg-1.min-1) and during infusion of saline. [6-14C]glucose was infused on both occasions. Breath was collected for determination of the specific activity of carbon dioxide, oxygen consumption, and carbon dioxide production. Glucose turnover during hyperinsulinemia was approximately eightfold higher than during saline infusion. During the final 1.5 h of the hyperinsulinemic glucose clamp, oxidation measured isotopically remained slightly but consistently lower (P less than 0.05) than that measured by indirect calorimetry (13.8 +/- 1.1 vs 16.5 +/- 1.7 mumol.kg 1.min-1, respectively). In contrast, during the saline infusion, glucose oxidation measured isotopically did not differ from that measured by indirect calorimetry (8.3 +/- 0.6 vs 7.2 +/- 2.8 mumol.kg-1.min-1, respectively). We conclude that although net glucose oxidation measured isotopically was slightly lower than that measured by indirect calorimetry, both techniques provide similar estimates of glucose oxidation over a wide range of glucose disposal. PMID- 1902347 TI - Structured lipid made from fish oil and medium-chain triglycerides alters tumor and host metabolism in Yoshida-sarcoma-bearing rats. AB - The effects of structured lipid composed of fish oil and medium-chain triglycerides (Fish/MCT) on tumor and the host metabolism was compared with conventional long-chain triglycerides (LCTs) in Yoshida-sarcoma-bearing rats receiving TPN for 3 d. The two parenterally fed groups were divided into two treatments, saline or tumor necrosis factor (TNF), given intravenously at 20 micrograms/kg body wt. Changes in tumor volume, body weight, urinary nitrogen, whole-body and tissue protein kinetics, and fatty acid composition were measured. The study revealed that Fish/MCT feeding inhibited tumor growth, which could be attributed to decreased tumor protein synthesis. Body weight and nitrogen were better maintained by Fish/MCT feeding. In addition, the effects of Fish/MCT on tumor growth were synergistic with TNF treatment. The results demonstrate that dietary fat composition can influence fatty acid compositions of tumor tissue as well as tumor protein kinetics after a short period of TPN feeding. PMID- 1902348 TI - Dietary treatment for familial hypercholesterolemia--differential effects of dietary soy protein according to the apolipoprotein E phenotypes. AB - Familial hypercholesterolemia, one form of type IIa hyperlipidemia, usually responds poorly to standard low-lipid diets. To define the responsiveness to a soy-protein diet in this disease, one homozygous and twenty heterozygous type IIa patients were submitted to a 4-wk traditional hypocholesterolemic diet followed by 4 wk in which animal protein was substituted with texturized soy protein. Soy was then withdrawn for a further 4 wk. No significant changes in plasma lipids were observed during low-lipid diets. The soy diet, however, caused a marked decrease in total (-20.8%) and low-density-lipoprotein (-25.8%) cholesterol and in apolipoprotein B (-14.1%). The plasma cholesterol reduction was higher in patients with apolipoprotein E3/E3 or E3/E4 vs an almost negligible effect on E3/E2. These results confirm that soy-protein diets can lower cholesterol in type IIa patients with familial disease. Data on the sensitivity of patients with different apo-E isoforms agree with recent hypotheses suggesting that soy proteins may activate B,E receptors. PMID- 1902349 TI - Mild orotic aciduria and uricosuria in severe trauma victims. AB - Hypermetabolic responses with respect to pyrimidine and purine kinetics in trauma victims were investigated during the catabolic phase before and after nutritional support. Orotic acid and uric acid excretions were measured in 32 adult, severely traumatized, hypermetabolic, and highly catabolic patients while they were receiving fluids with no calories or nitrogen. Patients were then fed intravenously amino acids and glucose or glucose alone or fed enterally for 5-6 d. Daily excretions of orotic acid, uric acid, urea, nitrogen, and creatinine were monitored. Mild orotic aciduria and uricosuria with hypouricemia were the basal-trauma responses. The significant (P = 0.001, r = 0.70) positive correlation between orotic and uric acid excretion demonstrates the parallelism between pyrimidine and purine metabolism. Feeding for 5-6 d could decrease but not readily abolish the injury-induced metabolic changes in nitrogen, pyrimidine, and purine metabolism. Glucose infusion alone may be sufficient to counteract the metabolic effects of trauma in the early flow phase of injury. PMID- 1902350 TI - Direct vasodilator effect of hyperventilation-induced hypocarbia in autonomic failure patients. AB - Hyperventilation produces small decreases in blood pressure in normal subjects and larger decreases in patients with autonomic failure. The authors studied the mechanism for this observation by measuring mean arterial pressure (MAP) and arterial blood gas (ABG) changes in eight patients with severe primary autonomic failure after various maneuvers designed to alter PaCO2, PaO2, and pH. Maneuvers included voluntary hyperventilation, breathing a 5% CO2/95% O2 mixture, breathing 12% O2, breathing through a 1 meter tube to increase dead space, breathing 100% O2, and infusion of 120 mEq NaHCO3 over 30 minutes. All maneuvers led to expected changes in ABGs. Voluntary hyperventilation lowered MAP by 23 +/- 4 (p less than 0.01) mmHg but MAP was raised 11 +/- 3 and 7 +/- 1 mmHg by hyperventilation resulting from increasing breathing dead space or from breathing 5% CO2, respectively. Breathing 100% O2 or 12% O2 had no significant effect on MAP, and NaHCO3 infusion raised MAP by 8 +/- 4 (p less than 0.05) mmHg. With all maneuvers, change in MAP correlated with change in PaCO2 (r = 0.72, p less than 0.001) and change in pH (r = -0.57, p less than 0.01) but not with PaO2. Multiple regression analysis showed that only changes in PaCO2 predicted the change in MAP for all maneuvers. The authors conclude that a decrease in PaCO2 causes the observed decreases in MAP with hyperventilation. This most likely represents a direct peripheral vasodilator effect of hypocarbia rather than a reflex or centrally-mediated mechanism since our patient population is characterized by inadequate or absent autonomic cardiovascular reflex responses. PMID- 1902351 TI - Hypophosphatemic osteomalacia in von Recklinghausen neurofibromatosis. AB - Skeletal lesions are not uncommon in von Recklinghausen neurofibromatosis. Most of them are considered to be dysplastic in nature. Association of osteomalacia or rickets with neurofibromatosis has been documented only rarely. Reported herein is a 40-year-old woman with known von Recklinghausen neurofibromatosis who presented with bone pain, multiple pseudofractures, marked increase in osteoid by bone biopsy, and hypophosphatemia with renal phosphate wasting. Treatment with oral phosphate and vitamin D was effective. A survey of the literature revealed that 34 similar cases have been reported in the past. Although the exact pathogenetic mechanism remains to be determined, osteomalacia in neurofibromatosis appears to be distinct from more common dysplastic skeletal affections of this disease, being characterized by later onset in adulthood as a rule, renal phosphate loss with hypophosphatemia, multiple pseudofractures in typical cases, and response to treatment with pharmacological dose of vitamin D with or without phosphate supplement. PMID- 1902352 TI - Definitions of infection for surveillance in long-term care facilities. PMID- 1902353 TI - B subunit of cholera toxin produced in Escherichia coli. AB - An engineered E. coli strain containing high expression level of CT-B subunits has been obtained by the application of recombinant DNA techniques. The B subunit can be secreted into the medium and reaches 20-40 micrograms/ml when this strain is incubated in a 50 l fermentation tank. The CT-B subunit purified with affinity chromatography in E. coli has the same characters as the natural CT-B subunit in molecular weight, N terminal amino acid analysis and antigenicity. The CT-B subunit has good immunogenicity and can be used as a preparation for protecting against diarrhea caused by V. cholera and enterotoxigenic E. coli. It can also be used as a vector for hepatins. PMID- 1902354 TI - Simultaneous transcranial Doppler sonography and cerebral blood flow measurements of cerebrovascular CO2-reactivity in patients with aneurysmal subarachnoid haemorrhage. AB - Transcranial Doppler sonography (TCD) flow velocities and cerebral blood flow (CBF) measurements were evaluated in 14 patients who had suffered a major aneurysmal subarachnoid hemorrhage (SAH). Cerebrovascular reactivity to hypocapnia was evaluated simultaneously by the two methods. The measurements were performed under general anaesthesia preoperatively, within 72 hours after the bleed, during normocapnia and hypocapnia. There was poor correlation between absolute values of hemispheric CBF and corresponding TCD mean flow velocity. Controlled hyperventilation was associated with a significant decrease in CBF as well as TCD flow velocity (p less than 0.001). In terms of reactivity indices the correlation between the two methods was poor and not significant (r = 0.33, p = 0.09). The principal differences between the methods are discussed as well as the application of TCD in the evaluation of cerebrovascular reactivity. PMID- 1902355 TI - Functional results after total or near total glossectomy with laryngeal preservation. AB - Locally advanced tongue cancer is a devastating disease for which there are limited therapeutic options that will result in a high rate of cure while preserving function. To determine the oncologic effectiveness of total or near total glossectomy with laryngeal preservation and the possibility of speech and swallowing rehabilitation following treatment, we reviewed our experience with 27 patients treated between 1982 and 1989. Twenty-four patients were eligible for 2 year follow-up and their disease-specific survival was 51%. Swallowing was achieved initially in 18 patients (67%), while 12 had successful long-term deglutition (44%). Oral communication was accomplished in 25 patients (92%). Significant aspiration occurred in three patients and was severe enough to require interval laryngectomy in two patients. The role of laryngeal suspension, palatal augmentation prosthesis, and videofluoroscopy as rehabilitation adjuncts for the total glossectomy patient are described. PMID- 1902356 TI - Tracheal granulation tissue. A study of bacteriology. AB - We prospectively examined 19 patients (21 laryngotracheal reconstructions) over a 6-month period to evaluate the bacteriology of granulation tissue present at the time of Teflon stent removal and at the first laryngoscopy several weeks later. The most frequently recovered isolates were viridans streptococci, Pseudomonas aeruginosa, nonhemolytic Streptococcus, and Staphylococcus aureus. All but one positive culture were polymicrobial. The amount of tissue did not correlate with the duration of stenting and the amount of granulation tissue and number of organisms decreased after stent removal. Further prospective study of the most appropriate antimicrobial therapy is needed. PMID- 1902357 TI - Periorbital hematoma secondary to sinusitis in a child. AB - Periorbital abscess secondary to sinusitis is a well-recognized entity in children. However, subperiosteal hematoma is extremely rare and has been reported in only four adult patients. This article presents the case of a 4-year-old girl with sinusitis, proptosis, and decreased visual acuity. Surgical exploration of the orbit revealed the presence of a large organizing subperiosteal hematoma that was drained. The presence of a periorbital hematoma should be suspected in patients with acute onset of proptosis and findings of a periorbital mass and sinusitis on computed tomographic scan. PMID- 1902359 TI - The Royal College of Nursing: seventy-five years strong. PMID- 1902358 TI - Synergistic effects of a calcium ionophore and activators of protein kinase C on epithelial paracellular permeability. AB - Oxidants reversibly increase the paracellular permeability of Madin Darby canine kidney (MDCK) epithelial cell monolayers, and the decrease in resistance occurs within 10 to 15 min of initiating oxidant exposure. Oxidants also initiate hydrolysis of phosphatidylinositol in MDCK cells, with resultant increases in diacylglycerol and inositol phosphates. Phorbol esters and synthetic diacylglycerols increase the paracellular permeability of MDCK monolayers with a time course similar to the oxidants. In contrast, calcium ionophores increase MDCK monolayer paracellular permeability only after 2 to 3 h of exposure. Because the products of the oxidant-initiated phospholipid hydrolysis would be likely to both activate protein kinase C and increase cell calcium, we asked if ionomycin, a calcium ionophore, and phorbol esters or diacylglycerols, activators of protein kinase C, might not act in concert to alter MDCK monolayer paracellular permeability. When ionomycin was added alone to MDCK monolayers, there was an increase in cell calcium, activation of a lumen negative current, a limited transitory decrease in transepithelial resistance, but no increase in mannitol flux across the monolayers. When phorbol dibutyrate (PDBU) or oleyl acetyl glycerol (OAG) were added to MDCK monolayers, there was no current activated, there was a progressive decrease in transepithelial resistance, and there was an increase in mannitol flux across the monolayers which was evident within 20 to 40 min of adding the agent. When 1 microM ionomycin was added to the monolayers along with PDBU or OAG, there was a synergistic increase in paracellular permeability of the monolayers when compared to addition of ionomycin, PDBU, or OAG alone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1902360 TI - High flyer?. Interview by Norah Casey. PMID- 1902361 TI - NHS reforms. Ready, steady, slow? PMID- 1902362 TI - World Health Organization. An awfully big adventure. Interview by Jane Salvage. PMID- 1902363 TI - Body pressures and bed surfaces. AB - Specialised beds which are designed to prevent unacceptably high levels of pressure loads on skin surfaces are frequently used in the management of patients with, or at risk of developing, pressure sores. This study compares the intersurface pressure on 'at risk' body sites of six subjects on a new design of water bed with those obtained from resting on a King's Fund bed. The findings show flotation on the water bed offers more effective support to body tissue than that provided by the King's Fund bed. PMID- 1902365 TI - The nuisance factor. PMID- 1902364 TI - Using Roy's model in a special hospital. AB - Using a nursing model to help systematise the care of a young patient in a special hospital resulted in tangible improvements in his behaviour, yet Francesca Miller found that it raised questions about the function and value of nursing for this client group. Her study reveals how she had to cope with her own negative feelings about the nature of her patient's offences and how the use of basic counselling skills, and encouraging the patient to take responsibility for his own care, achieved notable developments in his social skills. But despite this, she is left to ponder, 'at what cost?' PMID- 1902366 TI - ST depression and elevation. PMID- 1902367 TI - Opportunity and the charge nurse. AB - Nursing Standard has, over the past six weeks, produced a series of articles dealing with issues in ward management for charge nurses. Series co-ordinator Ros Brown now offers a postscript which acts as a conclusion for the series and reflects on the dilemmas and opportunities which face charge nurses as they enter into the world of purchasers and providers, hospital Trusts and PREPP. It is essential that the role of the charge nurse is not only preserved in this changing climate, she argues, but is cultivated, nurtured and recognised as an indispensable function. The future looks bright for those prepared to discard the habits of the past and grasp the challenges of the present. PMID- 1902368 TI - Influenza: virulence and management. AB - In the second of her articles on influenza, Marie Kedzierski stresses that the effects of this disease are not always transient and merely uncomfortable, but can lead to chronic and debilitating physical and mental illness. It is essential, she argues, to promote rest during the acute phase of viral illness in order to minimise the risk of future complications. PMID- 1902369 TI - Into the community. PMID- 1902370 TI - Working mothers. Easter barny. PMID- 1902371 TI - How to become an MP. PMID- 1902372 TI - The psychosocial context of HIV/AIDS. PMID- 1902373 TI - AIDS focus. Writing What Works? PMID- 1902374 TI - AIDS focus. Innocent virus guilty words. PMID- 1902375 TI - Management of dysthyroid eye disease. PMID- 1902376 TI - Crystallization and structure determination to 2.5-A resolution of the oxidized [2Fe-2S] ferredoxin isolated from Anabaena 7120. AB - The molecular structure of the oxidized form of the [2Fe-2S] ferredoxin isolated from the cyanobacterium Anabaena species strain PCC 7120 has been determined by X ray diffraction analysis to a nominal resolution of 2.5 A and refined to a crystallographic R factor of 18.7%. Crystals used in this investigation belong to the space group P2(1)2(1)2(1) with unit cell dimensions of a = 37.42 A, b = 38.12 A, and c = 147.12 A and two molecules in the asymmetric unit. The three dimensional structure of this ferredoxin was solved by a method that combined X ray data from one isomorphous heavy-atom derivative with noncrystallographic symmetry averaging and solvent flattening. As in other plant-type [2Fe-2S] ferredoxins, the iron-sulfur cluster is located toward the outer edge of the molecule, and the irons are tetrahedrally coordinated by both inorganic sulfurs and sulfurs provided by protein cysteine residues. The main secondary structural elements include four strands of beta-pleated sheet and three alpha-helical regions. PMID- 1902377 TI - Formation of prostaglandin synthase-iron-nitrosoalkane inhibitory complexes upon in situ oxidation of N-substituted hydroxylamines. AB - Various N-alkylhydroxylamines such as N-hydroxyamphetamine react with prostaglandin synthase (PGHS) from sheep seminal vesicles, with the formation of new complexes characterized by a Soret peak around 421 nm. These complexes are very stable toward O2 or dithionite but are destroyed upon oxidation by Fe(CN)6K3 with regeneration of starting PGHS-FeIII. Their spectral characteristics, chemical properties, and routes of formation (either by direct oxidation of RNHOH or by in situ reduction of RNO2 in the presence of dithionite) are very similar to those previously reported for nitrosoalkane complexes of hemoglobin-, myoglobin-, and cytochrome P-450-FeII. Their FeII-N(O)R structure was completely confirmed in the case of N-hydroxyamphetamine, both by extraction of the heme complex by butanone and by identification to authentic protoporphyrin IX-FeII N(O)-amphetamine, and by insertion of this authentic complex into apoPGHS. Phenylhydroxylamine also reacts with PGHS-FeIII to give a PGHS-FeII-N(O)Ph complex which is not stable in the presence of dithionite because of its weaker PGHS-FeII-N(O)R bond when compared to PGHS-FeII-nitrosoalkane complexes. The ability of various N-alkylhydroxylamines to form PGHS-FeII-N(O)R complexes greatly depends upon their hydrophobicity. Actually, CH3NHOH and C2H5NHOH are totally inactive whereas about 10 molar excess of N-hydroxyamphetamine and C6H5NHOH already lead to 50% complex formation. This is in favor of an hydrophobic environment of the heme in PGHS. Finally, PGHS engaged in such FeII nitrosoalkane complexes completely loses its dioxygenase activity, suggesting that N-substituted hydroxylamines or compounds that can be metabolized in vivo to give such hydroxylamines could act as strong PGHS inhibitors. PMID- 1902378 TI - Enzymological evidence for separate pathways for aflatoxin B1 and B2 biosynthesis. AB - Aflatoxins B1 (AFB1) and B2 (AFB2) are biologically active secondary metabolites of Aspergillus flavus and Aspergillus parasiticus. These toxins are synthesized by the fungi from pathway precursors: sterigmatocystin (ST)----O methylsterigmatocystin (OMST)----AFB1; dihydrosterigmatocystin (DHST)----dihydro O-methylsterigmatocystin (DHOMST)----AFB2. The late stages of AFB1 synthesis are carried out by two enzyme activities, a methyltransferase (MT) (ST----OMST), and an oxidoreductase (OR) (OMST----AFB1). Properties of the purified MT have been identified in a previous investigation [Bhatnagar et al. (1988) Prep. Biochem. 18, 321]. In the current study, the OR was partially purified (150-fold of specific activity) from fungal cell-free extracts and characterized with extended investigation of the late stages of AFB1 and AFB2 synthesis. Whole cells of an isolate of A. flavus (SRRC 141), which produce only AFB2, were able to produce AFB1 in ST and OMST feeding studies; the results suggested that the enzymes involved in AFB2 biosynthesis also carry out AFB1 synthesis. Substrate competition experiments carried out with the OR showed that an increasing concentration of either OMST or DHOMST in the presence of a fixed, nonsaturating concentration of either DHOMST or OMST, respectively, resulted in a decline in production of one aflatoxin (B1 or B2) with a corresponding increase in the synthesis of the other toxin (B2 or B1). OMST was a preferred substrate (Km, 1.2 microM) for the oxidoreductase as compared to DHOMST (Km, 13.4 microM). Similar, substrate competition experiments showed that ST (Km, 2.0 microM) was a preferred substrate over DHST (Km, 22.5 microM) for a homogeneous MT.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1902379 TI - Use of fluorescence energy transfer to characterize the compactness of the constant fragment of an immunoglobulin light chain in the early stage of folding. AB - The CL fragment of a type-kappa immunoglobulin light chain in which the C terminal cysteine residue was modified with N-(iodoacetyl)-N'-(5-sulfo-1 naphthyl)ethylenediamine (CL-AEDANS fragment) was prepared. This fragment has only one tryptophan residue at position 148. The compactness of the fragment whose intrachain disulfide bond was reduced in order for the tryptophan residue to fluoresce (reduced CL-AEDANS fragment) was studied in the early stages of refolding from 4 M guanidine hydrochloride by fluorescence energy transfer from Trp 148 to the AEDANS group. The AEDANS group attached to the SH group of a cysteine scarcely fluoresced when excited at 295 nm. For the reduced CL-AEDANS fragment, the fluorescence emission band of the Trp residue overlapped with the absorption band of the AEDANS group, and the fluorescence energy transfer was observed between Trp 148 and the AEDANS group in the absence of guanidine hydrochloride. In 4 M guanidine hydrochloride, the distance between the donor and the acceptor was larger, and the efficiency of the energy transfer became lower. The distance between Trp 148 and the AEDANS group for the intact protein estimated by using the energy-transfer data was in good agreement with that obtained by X-ray crystallographic analysis. By the use of fluorescence energy transfer, tryptophyl fluorescence, and circular dichroism at 218 nm, the kinetics of unfolding and refolding of the reduced fragment were studied. These three methods gave the same unfolding kinetic pattern. However, the refolding kinetics measured by fluorescence energy transfer were different from those measured by tryptophyl fluorescence and circular dichroism, the latter two giving the same kinetic pattern.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1902380 TI - Uniform 13C isotope labeling of proteins with sodium acetate for NMR studies: application to human carbonic anhydrase II. AB - Uniform double labeling of proteins for NMR studies can be prohibitively expensive, even with an efficient expression and purification scheme, due largely to the high cost of [13C6, 99%]glucose. We demonstrate here that uniformly (greater than 95%) 13C and 15N double-labeled proteins can be prepared for NMR structure/function studies by growing cells in defined media containing sodium [1,2-13C2, 99%]acetate as the sole carbon source and [15N, 99%]ammonium chloride as the sole nitrogen source. In addition, we demonstrate that this labeling scheme can be extended to include uniform carbon isotope labeling to any desired level (below 50%) by utilizing media containing equal amounts of sodium [1-13C, 99%]acetate and sodium [2-13C, 99%]acetate in conjunction with unlabeled sodium acetate. This technique is less labor intensive and more straightforward than labeling using isotope-enriched algal hydrolysates. These labeling schemes have been used to successfully prepare NMR quantities of isotopically enriched human carbonic anhydrase II. The activity and the 1H NMR spectra of the protein labeled by this technique are the same as those obtained from the protein produced from media containing labeled glucose; however, the cost of the sodium [1,2-13C2, 99%]acetate growth media is considerably less than the cost of the [13C6, 99%]glucose growth media. We report here the first published 13C and 15N NMR spectra of human carbonic anhydrase II as an important step leading to the assignment of this 29-kDa zinc metalloenzyme. PMID- 1902381 TI - Affinity labeling of folate transport proteins with the N-hydroxysuccinimide ester of the gamma-isomer of fluorescein-methotrexate. AB - Fluorescein-methotrexate, a derivative in which the fluorophore is linked via a diaminopentane spacer to either the alpha- or gamma-carboxyl group of the glutamate moiety in the drug [Gapski et al. (1975) J. Med. Chem. 18, 526-528], has been synthesized by an improved procedure and separated by DEAE-Trisacryl chromatography into the alpha- and gamma-isomers (alpha-F-MTX and gamma-F-MTX). Each isomer was characterized by mass spectrometry, elemental analysis, absorbance spectrum, TLC, and reversed-phase HPLC. Identity of the isomers was established by the following enzymatic criteria: (a) gamma-F-MTX (but not the alpha-isomer) was hydrolyzed at the pteroate-glutamate bond by carboxypeptidase G2 to yield 4-amino-4-deoxy-10-methylpteroate and gamma-glutamyldiaminopentane fluorescein; and (b) gamma-F-MTX was a much better inhibitor of human dihydrofolate reductase than the alpha-isomer (Ki values of 0.079 and 4.6 nM). alpha- and gamma-F-MTX were comparable as inhibitors (Ki values of 1.6 and 0.6 microM) of the transport system for reduced folates and MTX in L1210 cells, but the transporter in Lactobacillus casei was inhibited only by the gamma-isomer (Ki = 4.3 microM). The gamma-isomer, therefore, was selected for covalent labeling of proteins. When L. casei folate transport protein (18 kDa) was treated with gamma F-MTX that had been activated with N-hydroxysuccinimide (NHS), the protein was readily visualized as a fluorescent band on SDS-PAGE electrophoretograms. The probe was also able to detect the transporter in membranes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1902382 TI - Audit in general practice by a receptionist: a feasibility study. AB - OBJECTIVE: To examine whether audit can be done cost effectively by a practice's receptionist. DESIGN: The practice set goals for various aspects of care, and forms were devised for the receptionist to collect, analyse, and present data to assess whether these goals had been achieved in the previous year. SETTING: Six doctor practice in south London looking after 11,500 patients. MAIN OUTCOME MEASURES: Ability of receptionist to present data showing the level of attainment of the practice's goals; time spent on audit by receptionist each week. RESULTS: The practice set goals for immunisation; follow up of patients with abnormal cervical smears; frequency of recording of blood pressure and smoking habit; screening of patients over 75; care of diabetic patients and patients with serious mental illness; antenatal care; variations in workload; and availability of appointments. The receptionist was able to audit all these tasks in four hours a week; this increased her job satisfaction and extended her skills. A small amount of regular supervision was necessary--roughly 30 minutes a week in the first year of the study and 30 minutes a fortnight in the second--to ensure accuracy and deal with any difficulties that arose. CONCLUSION: The method developed enabled a receptionist to audit aspects of the practice cost effectively. There is great scope for enlarging the conventional role of the receptionist. PMID- 1902383 TI - Management of women referred to early pregnancy assessment unit: care and cost effectiveness. AB - OBJECTIVE: To assess the efficiency of an early pregnancy assessment unit in the care of women with bleeding or pain in early pregnancy. DESIGN: Analysis of women attending in the first year of the unit's operation and in the six months immediately before its introduction. SETTING: Early pregnancy assessment unit in a district general hospital serving a population of 310,000. PATIENTS: 1141 women referred with bleeding or pain in early pregnancy. MAIN OUTCOME MEASURES: Length of stay in hospital required for diagnosis and treatment. RESULTS: Before the unit was established the mean admission time was one and a half (range half to three) days for women who required no treatment and three (one and a half to five) days in women requiring evacuation of uterus. These times were reduced to two hours as an outpatient and one day respectively for most women after the unit was established. Between 318 and 505 women were estimated to have been saved from unnecessary admission, and 233 had their stay reduced; the associated saving was between pounds 95,000 and pounds 120,000 in one year. CONCLUSIONS: The early pregnancy assessment unit improved the quality of care and also produced considerable savings in financial and staff resources. PMID- 1902385 TI - Thrombolytic treatment for recurrent myocardial infarction. PMID- 1902384 TI - Clinical and financial audit of diagnostic protocols for lesions of the cerebellopontine angle. AB - OBJECTIVE: To assess the diagnostic efficiency and costs of protocols used for investigating patients with suspected lesions of the cerebellopontine angle. DESIGN: Prospective evaluation of tests of auditory brain stem responses and acoustic reflex thresholds, electronystagmography, and calorics. Positive test results were confirmed or refuted by high resolution computed tomography with intravenous enhancement. SETTING: Single general otolaryngology clinic in a teaching hospital. PATIENTS: 270 consecutive patients with sensorineural hearing loss requiring investigation to exclude a lesion of the cerebellopontine angle. MAIN OUTCOME MEASURES: Estimated costs of various diagnostic protocols and performance in detecting tumours of the cerebellopontine angle. RESULTS: Protocols including tests of auditory brain stem responses and acoustic reflex thresholds as sifting tests before computed tomography were clinically acceptable and presented considerable savings over the use of computed tomography in all patients (74,000 pounds or 84,000 pounds v 122,000 pounds). The use of electronystagmography and calorics could not be justified on clinical or financial grounds. CONCLUSIONS: Audiological tests of auditory brain stem responses and acoustic reflex thresholds followed by computed tomography constitute the most cost effective protocol for determining suspected lesions of the cerebellopontine angle. IMPLICATIONS: The cost effectiveness of diagnostic protocols should be evaluated throughout the health service. PMID- 1902386 TI - Effectiveness of ward based opportunistic immunisation policy. PMID- 1902387 TI - Concomitant pelvic irradiation, 5-fluorouracil and mitomycin C in the treatment of advanced cervical carcinoma. AB - This was a Phase II study of 24 late (FIGO) Stage IIb and 39 Stage III patients. External beam radiotherapy was given daily, five days a week, using 15 x 15 cm parallel opposed pelvic fields. The first 20 patients had 45.00 Gy mid-plane dose in 20 fractions, Days 1-28, the last 43 patients had 50.40 Gy in 28 fractions, Days 1-43. This was followed by an intracavitary boost of 17.00 Gy to Point A in two fractions over seven days. The first seven patients had concomitant 5 fluorouracil (5FU) 1 g/m2/day (maximum 1.5 g/day) Days 2-5, 30-33 and 57-60, with mitomycin C 10 mg/m2 (maximum 15 mg) Days 2 and 57. Two patients had WHO Grade 4 cytopenia, and only two were able to have full dose intensity. The 5FU dose was reduced to 0.8 g/m2/day, for Days 2-5 and 30-33; mitomycin C was given on Day 2 only. Treatment morbidity with the reduced chemotherapy intensity was comparable with that of radiotherapy alone. Median follow-up was 16 months (range 6-44). Median survival was 35 months. The results were compared with historical controls treated using the same radiation method alone. Two-year survival for late Stage IIb patients was 67% with the combination and 72% with radiotherapy alone; for Stage III, 67% and 49% respectively. Two-year pelvic control for late Stage IIb was 87% (combination) and 84% (radiotherapy alone) and for Stage III, 61% and 55% respectively. In contrast to reports from other centres, these results do not show an overall significant improvement on radiotherapy alone. A Phase III study may not be practicable. PMID- 1902389 TI - Tumour necrosis factor increases hepatic cell mass. AB - The effect of tumour necrosis factor (TNF) on hepatic cellularity was investigated in male Wistar rats maintained on total parenteral nutrition. Twenty eight rats were infused with TNF (2 x 10(5) units TNF-alpha kg-1 24 h-1) or saline (controls) for 6 days. Wet and dry liver weights and nitrogen content were significantly increased by TNF (P less than 0.001), indicating an increase in liver mass. A further 81 rats were infused with TNF (2 or 4 x 10(5) units kg-1 24 h-1) or saline over 1, 3 and 6 days. Total liver DNA and protein content and counts of hepatocyte mitosis were determined. Liver DNA and protein increased with dose of TNF and time (P less than 0.001), suggesting that TNF increased hepatic cellularity. Histological examination demonstrated no significant inflammatory infiltrate to account for the increased cell mass. However, the number of hepatocyte mitoses increased with dose of TNF and time (P less than 0.05), indicating that the increase in liver cellularity was due to increased hepatocyte cell number. TNF-induced hepatic hyperplasia appears to be an additional feature of the integrated host response to injury and infection. PMID- 1902388 TI - Results of long-term rice bran treatment on stone recurrence in hypercalciuric patients. AB - A series of 182 calcium stone formers with idiopathic hypercalciuria underwent treatment with rice bran for 1 to 94 months. Urinary calcium excretion was considerably reduced, but there was some increase in urinary phosphate and oxalate. Urinary excretion of magnesium and uric acid, serum calcium, magnesium, phosphate, uric acid, parathyroid hormone (PTH) and ALP was unaffected. There were no obvious changes in serum iron, zinc and copper even when patients were treated for long periods. Rice bran was well tolerated in almost all cases and there were no serious side effects; 49 patients have undergone treatment for more than 3 years (average duration of administration 5.09 years). The frequency of new stone formation was drastically reduced (individual stone formation rate (no./year) from 0.720 +/- 0.533 to 0.125 +/- 0.204; group stone formation rate (no./patient-year) from 0.721 to 0.120) compared with the 3-year period before treatment. During treatment, 61.2% of patients remained in remission. Although rice bran therapy should be effective in correcting absorptive hypercalciuria, there may be limits to the overall ability of rice bran monotherapy to prevent recurrence. PMID- 1902390 TI - The role of diabetic vascular alterations in the development of myocardial ischemia. AB - During the last fifteen years it has become evident that in diabetes there is an increased vasoconstrictor tendency in the arterial bed of different organs. This vasoconstrictor tendency is most expressed in the coronary arteries where sympathetic stimulation exerts vasodilation in the healthy and vasoconstriction in the diabetic arterial bed. Accordingly, myocardial tissue blood flow decreases during hypoxia in the diabetic, whereas it increases in nondiabetic states. Furthermore, 48 hours after ligation of the anterior left descending coronary artery the infarcted myocardial zone was extended below its first major oblique branch in diabetic dogs compared to nondiabetic ones. Since pretreatment with adrenergic antagonists or with cyclooxygenase inhibitors diminished considerably the increased vasoconstrictor tendency in the diabetic state alterations in the endothelium as well as in adrenergic vascular and prostaglandin mechanisms are involved in the pathomechanisms of this phenomenon. Moreover, after mechanical removal of the endothelial layer in coronary arterial strips the maximum force generated by diabetic vessels exceeded the maximum contraction produced by nondiabetic arteries, and the dose-response curve of diabetic arteries to phenylephrine was steeper than in nondiabetic strips. All these phenomena appeared at an early stage when macro- and microscopic alterations could not yet be observed in the vessels. Sodium nitrite or papaverine evoked similar vasodilation in the diabetic and nondiabetic coronary arterial bed. PMID- 1902391 TI - K+ channels and metabolic inhibition in cardiac cells. AB - Metabolic inhibition, whether it is caused by ischemia or hypoxia, is characterized by an important net K+ outward movement. The nature of the currents involved remains a subject of discussion. Good candidates among the many representatives of the large K+ channel family are the ATP-dependent and the Nai activated K+ channels. Arguments in favour of the ATP-dependent K+ channel will be presented and are based on: 1) the effect of oral antidiabetics on action potential duration during hypoxia; 2) an estimation of the proportion of channels that need to be activated; the channel itself can be activated at relatively high ATP concentrations, and 3) the rectifying properties of the activated current at the whole cell and single channel level. A Nai(+)-activated K+ current can be induced by intracellular dialysis with a solution containing a high Nai+ concentration. Induction is facilitated by simultaneous blockade of the Na+, K+ pump with ouabain or Ke(+)-free solution superfusion. The current shows marked outward rectifying properties. At the single channel level, the open probability was dependent on Nai+ and Na+, K+ pump activity. The channel showed inward rectification when Ki+ less than Ke+, but outward rectification when Ki+ greater than Ke+. The channel and the whole cell current showed similar blocking phenomena. The Nai(+)-activated K+ current may play an important role in action potential shortening during pump blockade and be responsible for a marked K+ loss in advanced ischemia. PMID- 1902392 TI - Enzyme immunoassay for (3-amino-1-methyl-5H-pyrido[4,3-b]indole), a tryptophan pyrolysate. AB - For evaluation of the cancer risk by the tryptophan pyrolysates a sensitive enzyme immunoassay for 3-amino-1-methyl-5H-pyrido-[4,3-b]indole (Trp-P-2), a mutagenic and carcinogenic substance, found in foods and biological fluids has been developed. The dose-response curve obtained was suitable for the determination of Trp-P-2 in the range of 20-800 pg. The immunoassay system was characterized to be satisfactorily specific as judged by cross-reactivity to gamma-carboline derivatives and their precursors, and comparison of immunoreactive Trp-P-2 levels in the basic and neutral fraction derived from pyrolyzed amino acids and related compounds. PMID- 1902393 TI - Role of nitric oxide in lysis of tumor cells by cytokine-activated endothelial cells. AB - The purpose of these studies was to determine whether nitric oxide produced by cytokine-activated murine lung vascular endothelial cells plays a role in their lytic destruction of M-5076 reticulum cell sarcoma. Vascular endothelial cells harvested from perfused lungs of mice were adapted to grow in culture. Cloned lines ascertained to be of endothelial origin were incubated in vitro with interferon gamma and tumor necrosis factor. Lysis of radiolabeled tumor cells and accumulation of nitrite in the culture medium were determined at several time points. The concentration of nitrite in the culture medium directly correlated with endothelial cell-mediated tumor cell lysis. Endothelial cells cultured in L arginine-free medium did not produce significant tumor cell lysis nor accumulation of nitrite in the medium. Both tumor cell lysis and nitrite accumulation were observed when the deficient medium was reconstituted with L arginine, suggesting that endothelial cell-mediated tumor lysis was dependent on L-arginine, a precursor of nitric oxide. Moreover, specific inhibition of nitric oxide synthesis by NG-methyl-L-arginine resulted in complete inhibition of endothelial cell-mediated lysis of the M-5076 reticulum cell sarcoma. Similarly, treatment of cytokine-activated endothelial cells with dexamethasone inhibited both target cell lysis and production of nitrite. Collectively, these results suggest that nitric oxide plays a major role in the lysis of tumor cells mediated by cytokine-activated endothelial cells. PMID- 1902394 TI - Lack of a cell cycle-dependent strand bias for mutations induced in the HPRT gene by (+/-)-7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10 tetrahydrobenzo(a)pyrene in excision repair-deficient human cells. AB - We showed previously that in repair-proficient human cells the location of the premutagenic lesion induced by (+-)-7 beta,8 alpha-dihydroxy-9 alpha,10 alpha epoxy-7,8,9,10- tetrahydrobenzo(a)pyrene (BPDE), namely, the guanine in a G.C base substitution, in mutants derived from cells treated at the beginning of S phase just when the hypoxanthine (guanine) phosphoribosyltransferase gene is replicated, differs significantly from their location in cells treated 12 h prior to the beginning of S phase (early G1 phase) (R-H. Chen et al., Proc. Natl. Acad. Sci. USA, 87:8680-8684, 1990). This suggests that the cells preferentially remove BPDE adducts from the transcribed strand. We have now determined the kinds and location of independent mutations induced by BPDE in the coding region of the hypoxanthine (guanine) phosphoribosyltransferase gene of synchronized repair deficient xeroderma pigmentosum cells (XP12BE, complementation group A), treated at S or in G1. Nineteen of 25 mutants derived from S-treated cells and 23 of 28 mutants from G1-treated cells contained base substitutions. Eighty-nine percent of these involved a G.C base pair, primarily G.C----T.A transversions. This is similar to the kinds of mutations we saw in the repair-proficient cells. However, in contrast to our earlier results, there was no change in strand distribution of premutagenic BPDE lesions. In both populations, approximately 26% of the base substitutions involving G.C base pairs had the G located in the transcribed strand, 5 of 18 in the S phase mutants, and 5 of 21 in the G1 phase mutants. These results support the hypothesis that the strong strand bias of induced mutations observed in the repair-proficient cells results from preferential repair of BPDE-induced DNA damage from the transcribed strand. PMID- 1902395 TI - Effects of the prostaglandin synthetase inhibitor indomethacin on tumorigenesis, tumor proliferation, cell kinetics, and receptor contents of 7,12 dimethylbenz(a)anthracene-induced mammary carcinoma in Sprague-Dawley rats fed a high- or low-fat diet. AB - The effects of indomethacin on tumorigenesis, tumor proliferation, cell kinetics, and receptor content of 7,12-dimethylbenz(a)anthracene-induced mammary carcinoma have been examined in female Sprague-Dawley rats. The rats were fed either a high fat (20% corn oil) or low-fat (0.5% corn oil) diet with or without 0.005% indomethacin starting 7 days after intragastric administration of a single dose of 5 mg 7,12-dimethylbenz(a)anthracene. The results demonstrated that indomethacin completely blocked the stimulatory effect of fat on tumorigenesis, as demonstrated by a decreased tumor incidence, a decreased number of tumors per group, and an increased latency. Contrary to what had been expected, however, indomethacin promoted tumor proliferation in both the high- and low-fat diet groups, as evidenced by an increased tumor size, an increased bromodeoxyuridine labeling index, and a decreased potential tumor-doubling time. No significant difference in either the estrogen receptor or progesterone receptor content of the tumor was noted. It can be concluded, therefore, that indomethacin significantly reduced tumorigenesis in the high-fat diet group but significantly promoted tumor proliferation in both the high- and low-fat diet groups. PMID- 1902396 TI - Macrophage-activating factor extracted from mycoplasmas. AB - Mycoplasmas (M. gallisepticum, chicken mycoplasmas), in concert with interferon gamma (IFN gamma), were effective in activating macrophages (M theta) to be tumoricidal. The M theta-activating capacity of mycoplasmas was maintained after treatment with heat. 0.1 M NaOH, 1 M HCl, or trypsin. M theta-activating factor was extracted from mycoplasmas with chloroform/methanol and water (Mf-B). Mf-B was also effective in activating M theta in the presence of IFN gamma. The threshold dose of Mf-B for M theta of ordinary C3H/He mice and that for those of C3H/HeJ mice, the latter being known to be low responders to bacterial lipopolysaccharide, were actually the same. This seems to indicate that the effectiveness of Mf-B was not attributable to possibly contaminating lipopolysaccharides, and that the pathway of activity of Mf-B is different from that of lipopolysaccharides. Since the M theta-activating principle was only a very small part of Mf-B, we have not yet succeeded in identifying it, but there was no evidence that it was protein, nucleic acid, sugar, or lipid. The cytotoxicity of M theta activated by Mf-B plus IFN gamma was dependent on L arginine in the culture, suggesting that arginine metabolites are involved in M theta cytotoxicity. Mf-B induced a small amount of tumor necrosis factor in M theta, and this induction was markedly enhanced by IFN gamma. PMID- 1902398 TI - Seminars in thrombosis, thrombolysis and vascular biology. 1. The vascular endothelium. AB - The vascular endothelium, once believed to act solely as a mechanical barrier is, in fact, the body's most active paracrine organ serving a vital role in vasomotion and thromboresistance. Vasoactive compounds such as prostacyclin and endothelium-derived relaxing factor maintain coronary blood flow in response to physiologic demands, while their antiplatelet effects act along with tissue plasminogen activator and heparin-like species to prevent local thrombus formation. Structural and functional endothelial abnormalities may predispose to vascular thrombosis or impair normal vasodilatory responses to increasing metabolic demands. Acquired endothelial dysfunction following coronary reperfusion, aortocoronary bypass grafting and balloon angioplasty plays a vital role in short- and long-term patient outcome. Future therapies in cardiovascular disease must consider strategies to preserve and facilitate the structural and functional integrity of the vascular endothelium. PMID- 1902397 TI - Cytotoxic and noncytotoxic mechanisms involved in the in vitro anti-leukaemia effects of T cell clones established from a chronic myelogenous leukaemia patient during treatment in vivo with interferon alpha. AB - T cell clones derived from a chronic myelogenous leukaemia (CML) patient during interferon alpha (IFN alpha, Wellferon) biotherapy preferentially lysed autologous rather than allogeneic CML target cells in an apparently MHC unrestricted fashion, but also lysed bone marrow cells from certain normal donors regardless of whether or not they shared HLA antigens with the patient. Although T cell clones inhibited both CML and normal bone marrow in the colony-forming assay, they blocked proliferation of CML cells more efficiently than bone marrow cells. This inhibitory effect was mediated at least in part by the tumour necrosis factor alpha (TNF alpha) and IFN gamma secreted by the clones. Antisera to these cytokines partially prevented inhibition. Involvement of additional factors is also suggested in blocking CML cell proliferation because this was not 100% inhibited even by a combination of TNF alpha and IFN gamma. In addition, most clones failed strongly to block the proliferation of normal bone marrow cells, which were susceptible to inhibition by these cytokines. PMID- 1902399 TI - A study of cytokine production in acute graft-vs-host disease. AB - The role of cytokines in the development of acute graft-vs-host disease (GVHD) was investigated in B6AF1 mice that were injected with parental A/J lymphocytes. Splenocytes from GVH mice exhibited an increased capacity to produce interleukin (IL)-1, IL-6, and TNF-a when stimulated in culture with lipopolysaccharide (LPS). This enhanced capacity was diminished following in vivo treatment with immunosuppressive drugs. Concanavalin A-stimulated GVH spleen cells produced significantly lower levels of IL-2 but higher levels of interferon-gamma (IFN gamma) than did syngeneic spleen cells. Immunosuppressive therapy in vivo increased the capacity of GVH spleen cells to produce IL-2. However, immunosuppressants differed in their effects on IFN-gamma production. Sch 24937 (6-bromo-5-chloro-2-[1-(methylsulfonyl)acetyl] 3-(2-pyridyl)indole) enhanced or had no effect while cyclosporin A consistently decreased the capacity of splenocytes to produce this lymphokine. These results indicate that the capacity of GVH splenocytes for cytokine production can be differentially affected by the actions of some pharmacological agents. The data also indicate that there may be differential regulation of the production of IL-2 and IFN-gamma by the Th1 subset in the GVH spleen. PMID- 1902400 TI - Rejection of allogeneic tumor is not determined by host responses to MHC class I molecules and is mediated by CD4-CD8+ T lymphocytes that are not lytic for the tumor. AB - In previous studies, the murine SaI (A/J derived, KkDd) sarcoma was transfected with the allogeneic MHC class I H-2Kb gene, and expressed high levels of H-2Kb antigen. Contrary to expectations, the tumor cells expressing the alloantigen (SKB3.1M tumor cells) were not rejected by autologous A/J mice. Because these results contradict the laws of transplantation immunology, the present studies were undertaken to examine the immunogenicity of SKB3.1M and SaI cells in allogeneic hosts. Similar to SKB3.1M, SaI cells are lethal in some allogeneic strains, despite tumor-host MHC class I incompatibilities. Tumor challenges of SKB3.1M and SaI cells, however induce MHC class I-specific antibodies and CTL in both tumor-resistant and -susceptible hosts. Although the tumors induce specific CTL, tumor cells are not lysed in vitro by these CTL, suggesting that the tumor cells are resistant to CTL-mediated lysis. Since growth of these tumors does not follow the classical rules of allograft transplantation, and because the tumor is not susceptible to CTL-mediated lysis, we have used Winn assays to identify the effector lymphocyte(s) responsible for SaI rejection. Depletion studies demonstrate that the effector cell is a CD4-CD8+ T lymphocyte. Collectively these studies suggest that the host's response to MHC class I alloantigens of SKB3.1M and SaI cells does not determine tumor rejection, and that effector cells other than classically defined CTL, but with the CD4-CD8+ phenotype, can mediate tumor specific immunity. PMID- 1902401 TI - Cytokines in the central nervous system of mice during chronic relapsing experimental allergic encephalomyelitis. AB - Clinical disease phases of chronic relapsing experimental allergic encephalomyelitis (CREAE) in the Biozzi AB/H mouse model are associated with extensive cellular infiltration of the central nervous system, principally the spinal cord. The activation of these cells is further suggested by the immunocytochemical demonstration of cytokines (migration inhibition factor, interferon-gamma, tumour necrosis factor-alpha, and interleukins 1, 2, and 3) within these infiltrates. The in vitro functions attributed to these cytokines indicate their potential role in cell recruitment, activation, and differentiation of the ongoing immune response which could contribute to the pathogenesis of disease. PMID- 1902402 TI - Continuous end-tidal CO2 sampling within the proximal endotracheal tube estimates arterial CO2 tension in infants. AB - End-tidal CO2 (ETCO2) sampled using a 22-gauge needle inserted through the wall of the proximal endotracheal tube was compared with ETCO2 obtained from the standard proximal connector to determine which was the more accurate sampling site for estimation of arterial CO2 tension (PaCO2). Fourteen infants were anaesthetized and their lungs ventilated using a Drager ventilator and a paediatric circle system. Blood gas determination of PaCO2 was obtained from an arterial catheter and compared with continuous sampling of ETCO2 analyzed by raman spectroscopy. The PaCO2 (35.3 +/- 4.9 mmHg, x +/- SD) was not different from the ETCO2 sampled within the proximal endotracheal tube (34.7 +/- 3.8 mmHg), but was greater (P less than 0.05) than the ETCO2 at the proximal connector (31.6 +/- 4.0 mmHg). We conclude that in infants during ventilation with a circle system, the PaCO2 can be accurately assessed by continuous sampling of ETCO2 from the proximal endotracheal tube. PMID- 1902403 TI - Negative arterial to end-tidal gradients. PMID- 1902404 TI - A randomized comparison of intravenous heparin with oral aspirin and dipyridamole 24 hours after recombinant tissue-type plasminogen activator for acute myocardial infarction. National Heart Foundation of Australia Coronary Thrombolysis Group. AB - BACKGROUND: This study addressed the need for heparin administration to be continued for more than 24 hours after coronary thrombolysis with recombinant tissue-type plasminogen activator (rt-PA). METHODS AND RESULTS: A total of 241 patients with acute myocardial infarction were treated with 100 mg rt-PA and a bolus of 5,000 units i.v. heparin followed by 1,000 units/hr i.v. heparin for 24 hours. At 24 hours, 202 patients were randomized to continue intravenous heparin therapy (n = 99) in full dosage or to discontinue heparin therapy and begin an oral antiplatelet regimen of aspirin (300 mg/day) and dipyridamole (300 mg/day) (n = 103). On prospective recording, there were no differences in the pattern of chest pain, reinfarction, or bleeding complications. Coronary angiography on cardiac catheterization at 7-10 days showed no differences in patency of the infarct-related artery. The proportion of patients with total occlusion (TIMI grade 0-1) of the infarct-related artery was 18.9% in the heparin group and 19.8% in the aspirin and dipyridamole group. In the patients with an incompletely occluded infarct-related artery, the lumen was reduced by 69 +/- 2% of normal in the heparin group and 67 +/- 2% in the aspirin and dipyridamole group. Left ventricular function assessed on cardiac catheterization and radionuclide study at day 2 and at 1 month showed no differences between the two groups. Left ventricular ejection fraction on radionuclide ventriculography at 1 month was 52.4 +/- 1.2% in the heparin group and 51.9 +/- 1.2% in the aspirin and dipyridamole group. CONCLUSIONS: We conclude that heparin therapy can be discontinued 24 hours after rt-PA therapy and replaced with an oral antiplatelet regimen without any adverse effects on chest pain, reinfarction, coronary patency, or left ventricular function. PMID- 1902406 TI - Evidence for reduced fibrinolytic activity in unstable angina at rest. Clinical, biochemical, and angiographic correlates. AB - BACKGROUND: The goal of this study was to evaluate the role of the fibrinolytic system in patients with unstable angina at rest associated with transient electrocardiographic changes. METHODS AND RESULTS: Tissue plasminogen activator activity in plasma was comparable among patients with unstable angina (n = 17), patients with stable exertional angina (n = 10), and control patients with normal coronary arteriograms (n = 8). In contrast, plasminogen activator inhibitor-1 (PAI-1) activity in plasma was elevated in the unstable angina group (21.67 +/- 9.52 AU/ml) as compared with either the stable angina group (12.01 +/- 7.06 AU/ml, p less than 0.02) or the controls (12.49 +/- 8.54 AU/ml, p less than 0.02). Coronary angiography performed within 24 hours after the last anginal episode showed a similar extent of coronary artery disease in the unstable and stable angina groups. However, intracoronary thrombi were observed in eight patients in the unstable angina group while no thrombus was noted in the stable angina group (chi 2 = 7.22, p less than 0.01). CONCLUSIONS: We conclude that patients with unstable angina at rest have a reduced fibrinolytic activity and an increased incidence of intracoronary thrombi. It is postulated that elevated PAI 1 activity in the presence of coronary arterial wall injury may be an important factor leading to the development of acute coronary syndromes. PMID- 1902405 TI - Evaluation of combination thrombolytic therapy and timing of cardiac catheterization in acute myocardial infarction. Results of thrombolysis and angioplasty in myocardial infarction--phase 5 randomized trial. TAMI Study Group. AB - Recent trials of myocardial reperfusion using single-agent thrombolytic therapy and sequential cardiac catheterization have supported a conservative approach to the patient with acute myocardial infarction. To evaluate combination thrombolytic therapy and the role of a previously untested strategy for the aggressive use of cardiac catheterization, we performed a multicenter clinical trial with a 3 x 2 factorial design in which 575 patients were randomly allocated to one of three drug regimens--tissue-type plasminogen activator (t-PA) (n = 191), urokinase (n = 190), or both (n = 194) - and one of two catheterization strategies--immediate catheterization with angioplasty for failed thrombolysis (n = 287) or deferred predischarge catheterization on days 5-10 (n = 288). Patients with contraindications to thrombolytic therapy, cardiogenic shock, or age of more than 75 years were excluded. Global left ventricular ejection fraction was well preserved and almost identical at predischarge catheterization (54%), regardless of the catheterization or thrombolytic strategy used (p = 0.98). Combination thrombolytic therapy was associated with a less complicated clinical course, most clearly documented by a lower rate of reocclusion (2%) compared with urokinase (7%) and t-PA (12%) (p = 0.04) and a lower rate of recurrent ischemia (25%) compared with urokinase (35%) and t-PA (31%). When a composite clinical end point (e.g., death, stroke, reinfarction, reocclusion, heart failure, or recurrent ischemia) was examined, combination thrombolytic therapy was associated with greater freedom from any adverse event (68%) compared with either single agent (urokinase, 55%; t-PA, 60%) (p = 0.04) and with a less complicated clinical course when the composite clinical end points were ranked according to clinical severity (p = 0.024). Early patency rates were greater with combination therapy, although predischarge patency rates after considering interventions to maintain patency were similar among drug regimens. No difference in bleeding complication rates was observed with any thrombolytic regimen. The aggressive catheterization strategy led to an overall early patency rate of 96% and a predischarge patency rate of 94% compared with a 90% predischarge patency in the conservative strategy (p = 0.065). The aggressive strategy improved regional wall motion in the infarct region (-2.16 SDs/chord) compared with deferred catheterization (-2.49 SDs/chord) (p = 0.004). More patients treated with the aggressive strategy were free from adverse outcomes (67% versus 55% in the conservative strategy, p = 0.004), and the clinical course was less complicated when the adverse outcomes were ranked according to severity (p = 0.016). No significant increase in use of blood products resulted from the aggressive strategy.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1902407 TI - Effects of physical conditioning on fibrinolytic variables and fibrinogen in young and old healthy adults. AB - BACKGROUND: The effects of 6 months of intensive endurance exercise training on resting tissue-type plasminogen activator (t-PA) activity, plasminogen activator inhibitor type 1 (PAI-1) activity, t-PA antigen, and fibrinogen were studied in 10 young (24-30 years) and in 13 old male subjects (60-82 years). METHODS AND RESULTS: After training, maximum oxygen consumption was increased in the young group by 18% (44.9 +/- 5.0 to 52.9 +/- 6.6 ml/kg/min, p less than 0.001), whereas it was increased in the old group by 22% (29.0 +/- 4.2 to 35.5 +/- 3.6 ml/kg/min, p less than 0.001). The young group had no significant changes in any of the measured variables, whereas the old group had a 39% increase in t-PA activity (0.82 +/- 0.47 to 1.14 +/- 0.42 IU/ml, p less than 0.03), a 141% increase in the percentage of t-PA in the active form (11.1 +/- 7.7 to 26.8 +/- 15.1%, p less than 0.01), a 58% decrease in PAI-1 activity (8.4 +/- 4.9 to 3.5 +/- 1.7 AU/ml, p less than 0.01), and a 13% decrease in fibrinogen (3.57 +/- 0.79 to 3.11 +/- 0.52 g/l, p less than 0.01). CONCLUSIONS: We conclude that intensive exercise training enhances resting t-PA activity and reduces fibrinogen and PAI-1 activity in older men. These effects are potential mechanisms by which habitual physical activity might reduce the risk of cardiovascular disease. PMID- 1902408 TI - A long-term dose-response study of somatostatin analogue (SMS 201-995, octreotide) in resistant acromegaly. AB - Ten acromegalic subjects were studied in a trial designed to ascertain the optimum dosage of the somatostatin analogue SMS 201-995 (octreotide) in active acromegaly. Twenty-four-hour growth hormone (GH) profiles were assessed monthly for 6 months and again after 1 year of continuous therapy. After basal assessment octreotide was administered subcutaneously at a dose of 100 micrograms three times a day throughout the first month. The dose was increased by 300 micrograms/day at monthly intervals to a maximum of 1500 micrograms/day, unless serum GH fell to within set criteria. Eight patients completed the trial. One patient withdrew because of intractable diarrhoea while another died of causes related to his acromegaly and we have no evidence that octreotide played any part in his death. Mean 24-h GH fell from a basal level of 34.3 +/- SEM 7.6 mU/l to 8.0 +/- 1.3 mU/l (P less than 0.05) after 6 months. At 1 month (300 micrograms/day) mean GH was 13.6 +/- 2.2 mU/l and at 2 months (600 micrograms/day) 10.8 +/- 2.2 mU/l (P less than 0.05 vs 300 micrograms/day dose), and at 5 months (1500 micrograms/day) 11.3 +/- 2.0 mU/l (all P less than 0.05 vs basal). Analysis of group means revealed no significant difference between any dose schedules above 600 micrograms/day. After 1 year the mean GH of the group (n = 8) was 7.5 +/- 1.3 mU/l (P less than 0.05 vs basal). Three patients developed a deterioration and one an improvement in their glucose tolerance and three developed asymptomatic gallstones during the year of therapy. In conclusion, octreotide lowered GH levels in acromegaly over a 1-year period. We found no evidence that routinely increasing the dose beyond 600 micrograms/day was helpful. PMID- 1902410 TI - The effect of aldose reductase inhibition with ponalrestat on the width of the capillary basement membrane in diabetes mellitus. AB - There is evidence to suggest that hyperglycemia is required for the development of the microvascular complications of diabetes. However, the precise mechanism by which hyperglycemia might cause diabetic complications is not completely clear. One possibility is the increased activity of the polyol pathway. Capillary basement membrane thickness is a hallmark histological finding in diabetic microangiopathy. Previous studies in experimental models of diabetes have related the polyol pathway with the thickness of basement membrane in retinal capillaries. To study the effect of aldose reductase inhibition with ponalrestat on the width of the skeletal muscle capillary basement membrane in subjects with diabetes, we measured the capillary basement membrane width in 55 subjects with diabetes in a double masked, placebo controlled randomized trial over a period of 18 months. Twenty-nine patients received ponalrestat (two 300 mg tablets daily) and twenty-six received placebo tablets. The age, sex distribution, type and duration of diabetes were similar in both groups. The glycosylated hemoglobin remained at a constant level throughout the study in both groups. The baseline capillary basement membrane width of the ponalrestat group was 3134 +/- 146 A, it was 3074 +/- 226 A at month 12 and 2548 +/- 182 A at month 18 (P less than 0.001 vs baseline value). The placebo group also had a significant reduction in the width of the capillary basement membrane, from a baseline value of 3026 +/- 147 A to 2818 +/- 144 A at month 12 and 2618 +/- 156 A at month 18 (P less than 0.001 vs baseline value). There was no statistical difference in the capillary basement membrane width between the two groups at any time point.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1902409 TI - PAF-induced bowel necrosis. Effects of vasodilators. AB - Ischemic bowel necrosis in the rat is produced by injecting platelet-activating factor (PAF) intravenously. Since intestinal hypoperfusion is observed after PAF injection, we hypothesize that mesenteric vasoconstriction is the mechanism of bowel injury. We thus studied the effects of vasodilators in this model. We found that: (1) Phenoxybenzamine, prazosin, ICI 198615 (leukotriene antagonist) and PGE1 counteracted the PAF-induced mesenteric flow reduction and ameliorated the bowel injury. However, phenoxybenzamine and prazosin were relatively ineffective in correcting PAF-induced hypotension, showing that bowel injury can be prevented independently of the hypotensive state. (2) Nitroglycerin failed to prevent bowel injury, although it improved the mesenteric blood flow. Thus, in opposition to our initial hypothesis, correction of the mesenteric flow reduction induced by PAF does not always prevent intestineal necrosis. (3) Only phenoxybenzamine, prazosin, ICI 198615, and PGE1 ameliorated PAF-induced hemoconcentration and bowel injury. This suggests a correlation between vascular injury (expressed by "leaky" vessels and the consequent hemoconcentration) and bowel necrosis. (4) Although both nitroglycerin and hydralazine relax smooth muscle, hydralazine seemed to aggravate bowel necrosis. The mechanism remains unclear. PMID- 1902411 TI - Comparative effects of diet or glibenclamide on insulin secretion and action in non-obese NIDDM. AB - We compared the effects of dietary treatment (D) and diet plus glibenclamide (DPG), for 3 weeks, on glycemia, insulin secretion and action in 2 groups of non obese patients with NIDDM matched for fasting plasma glucose level. Fasting glycemia decreased in both groups with greater reductions after DPG (n = 7, 10.0 +/- 0.6 to 6.3 + 0.3 mmol/l, M +/- SEM, P less than 0.02) than after D (n = 7, 10.1 +/- 0.8 to 8.7 +/- 0.7 mmol/l, M +/- SEM, P less than 0.02). The magnitude of day-time elevation of plasma glucose over the fasting level, however, was reduced only after DPG. DPG but not D improved the plasma insulin response to glucose ingestion and in vivo insulin action measured by insulin tolerance test with unaltered erythrocyte 125I-insulin binding. This might indicate potentiation of insulin action at post-receptor binding steps. Improvements in in vivo insulin action and in insulin secretion after DPG closely correlated with decrease in fasting glycemia and reduction in the day-time elevation of plasma glucose levels, respectively. In conclusion, diet improved glycemic control in non-obese patients with NIDDM mainly by reducing fasting glycemia, although the mechanism remains unknown. Glibenclamide added to the diet further decreased fasting glycemia by improving in vivo insulin action and reduced the magnitude of day time elevation of plasma glucose by enhancing endogenous insulin secretion. PMID- 1902414 TI - Micronuclei in mouse skin cells following in vivo exposure to benzo[a]pyrene, 7,12-dimethylbenz[a]anthracene, chrysene, pyrene and urethane. AB - Detection of micronuclei (MN) in skin cells from HRA/Skh hairless mice treated with chemical or physical agents may prove informative in qualitative and quantitative studies of skin carcinogenesis. MN induction and cell survival were estimated in cytokinesis-blocked keratinocytes, cultured for 4 days in vitro, after a single topical dose of various organic compounds. Treatment with 2.56 micrograms (10 nmol) 7,12-dimethylbenz[a] anthracene (DMBA) resulted in maximal MN induction in cells removed from skin 12-24 hr after topical administration (79 88 MN/1,000 cells compared with 10-16 MN/1,000 cells in acetone-treated controls). Even in cells removed only 1 hr after DMBA treatment, a significant increase in MN was evident. However, to allow sufficient time for metabolic activation, a sampling time for of 24 hr was adopted for all test substances. Dose-dependent increases in MN were observed with DMBA, benzo[a]pyrene, chrysene, and urethane. Increased numbers of micronucleated cells were detected at the lowest doses administered in the present study (0.128, 0.5, 50, and 50 micrograms, respectively). Although reduced cell recovery occurred following exposure of mice to acetone, pyrene, and other chemicals, there was no evidence that cytotoxicity contributed to MN scored in keratinocytes. Moreover, the probable noncarcinogen, pyrene, failed to induce MN at doses from 2.5 micrograms to 2.5 mg/mouse. These results show that it is possible to assess chemical exposure in skin by measuring cell survival and skin genotoxicity by measuring MN induction in cultured keratinocytes. The available data suggest that MN induction may be a useful indicator of the carcinogenic potential of chemicals applied to the skin. PMID- 1902412 TI - N-myc disrupts protein kinase C-mediated signal transduction in neuroblastoma. AB - In neuroblastoma, amplification of the N-myc gene is closely correlated with increased metastatic ability. The mechanism by which N-myc acts to increase neuroblastoma malignancy is poorly understood as yet. It is shown here that transfection of N-myc in a neuroblastoma cell line causes suppression of one isoform of protein kinase C, named delta, and induction of an unusual type of protein kinase C, named zeta. N-myc-transfected neuroblastoma cells were found to be blocked in the activation of both c-fos mRNA and the NF-kappa B transcription factor by phorbol ester. Introduction of a protein kinase C expression vector in N-myc transfected neuroblastoma cells restored inducibility of both c-fos and NF kappa B by phorbol ester. These observations indicate that changes in protein kinase C gene expression significantly alter the response of N-myc-amplified neuroblastomas to a variety of external signals. PMID- 1902415 TI - Responses of the L5178Y mouse Lymphoma cell forward mutation assay. V: 27 coded chemicals. AB - Twenty-seven chemicals were tested for their mutagenic potential in the L5178Y tk+/tk- mouse lymphoma cell forward mutation assay using procedures based upon those described by McGregor et al. (McGregor DB, Martin R, Cattanach P, Edwards I, McBride D, Caspary WJ (1987): Environ Mol Mutagen 9:143-160). Cultures were exposed to the chemicals for 4 hr, then cultured for 2 days before plating in soft agar with or without trifluorothymidine (TFT), 3 micrograms/ml. The chemicals were tested at least twice. Statistically significant responses were obtained with acid orange 10, aniline, benzaldehyde, o-chloroaniline, chlorodibromomethane, cytembena, 1,2-dibromo-4-(1,2-dibromomethyl) cyclohexane, dieldrin, lithocholic acid, oxytetracycline, phenazopyridine HCl, 1-phenyl-3 methyl-5-pyrazolone, sodium diethyldithiocarbamate, solvent yellow 14, tetraethylthiuram disulfide (disulfiram), 2,4-toluene diisocyanate, and 2,6 toluene diisocyanate. Apart from phenazopyridine HCl, acid orange 10, and solvent yellow 14, rat liver S9 mix was not a requirement for the mutagenic activity of these compounds. Chemical not identified as mutagens were N-4 acetylaminofluorene, chlorpheniramine maleate, chloropropamide, 1,4-dioxane, endrin, ethylene glycol, iron dextran, methapyrilene, sodium(2-ethylhexyl)alcohol PMID- 1902413 TI - Association of CD8 with p56lck is required for early T cell signalling events. AB - The human CD8 glycoprotein functions as a co-receptor during T cell activation by both binding to MHC class I and transducing a transmembrane signal. The ability of CD8 to transduce a signal is mediated in part by its association with the protein tyrosine kinase p56lck. Using a panel of human CD8 alpha mutants, we demonstrated that the presence of a functional p56lck binding site is required for the early signalling events transduced by CD8, including increased [Ca2+]i and protein tyrosine phosphorylation. In addition, our results demonstrate that wild-type and all mutant forms of CD8 alpha have an inhibitory effect on signal transduction after CD3-CD3 or CD3-CD4 crosslinking when transfected into the (CD3+, CD4+, CD8-) H9 T cell line, suggesting that intermolecular associations of CD8, independent of its association with p56lck, are responsible for this effect. Signalling through CD4 or CD8 in a double positive thymocyte may therefore be different than in a single positive thymocyte or mature T cell. PMID- 1902416 TI - Transurethral treatment of bladder diverticula. AB - We performed transurethral fulguration of the diverticular mucosa and incision of the diverticular neck in combination with transurethral prostatectomy or bladder neck resection to treat all aspects of diverticula in 9 patients. Eight cases with bladder outlet obstruction, involving 2 cases of large diverticula, have been successfully treated. A case with neurogenic bladder has failed. We found the transurethral procedure to be equally effective as open operation. PMID- 1902417 TI - Recurrence of superficial bladder tumors in prostatic urethra. AB - Of our 276 patients with superficial bladder carcinoma, 242 were male, and 36 of these had recurrence in prostatic urethra, 26 with macroscopic tumors, and 10 with tumors in situ (TIS). These recurrences represent an incidence of 13.3%, with an average follow-up of 34.3 months. When the urethral tumor was limited to the mucosa, we chose conservative therapy, and the patients entered a random program with Mitomycin or Adriamycin administered endovesically. With this program, we could control the disease in 59.3% of the patients. However, 22.2% of them had recurrence with prostatic stromal infiltration, so that we performed a more exhaustive exploration of the prostate, taking biopsies not only at the 5 and 7 o'clock positions, but also making a wider resection in order to find the incipient infiltration of the prostatic stroma, and trying to avoid a possible understaging. When the urethral tumor had infiltrated the prostatic stroma, we performed cystoprostatourethrectomy, getting a survival rate free of disease of 40%. An association with vesical TIS was detected in 61.1% of these patients, with terminal ureteral tumor in 8.3% and with the anterior urethra in 11.1%, showing the diffuse pattern of the disease. We conclude that when recurrence of prostatic urethra is present, it is necessary to monitor the whole urothelium during follow-up. PMID- 1902418 TI - Carcinoma in situ associated with superficial bladder tumor. AB - In a sample of 306 patients with superficial bladder tumors (Ta, Tl), 48 were affected by associated carcinoma in situ (TIS). We included 40 of them in a random program with Mitomycin C or Adriamycin, administered endovesically. We found that those patients with associated TIS whose progression rate had increased to 37.1% compared to 8.8% in the original series (p less than 0.01), had a worse prognosis. Besides, 10 of them required radical cystectomy. With this chemotherapy program, we achieved a high rate of complete response (70%), but its duration was limited by a recurrence rate of 42.9%, with a time free of disease of 26.2 months. In the whole group, the survival rate free of disease was 77.5%, with an average follow-up of 37.3 months. On the other hand, we found extravesical recurrences not only in the prostatic urethra (13; 32.5%) but also at the end of the ureter (3; 7.5%). PMID- 1902419 TI - The effect of danazol on pulsatile gonadotropin secretion in women with endometriosis. AB - OBJECTIVE: To determine whether the effect of danazol on gonadotropin pulsatility was due to a direct effect of the drug or the suppression in the estradiol (E2) levels. DESIGN: Prospective analysis of serial blood samples at 10-minute intervals for 5 hours on days 3, 4, or 5 of the control cycle and 2 months after the start of danazol treatment. SETTING: Tertiary institutional outpatient care. PATIENTS, PARTICIPANTS: Six eugonadal women with minimal endometriosis. INTERVENTIONS: Oral administration of danazol, 200 mg three times daily. MAIN OUTCOME MEASURES: Gonadotropin mean levels, pulse frequency, and amplitude. RESULTS: The mean level of E2 was the same in the control cycle as that during danazol treatment (170 pmol/L). Danazol administration resulted in a 16% increase in the mean luteinizing hormone (LH) pulse amplitude (95% confidence interval [CI] 6% to 26%, P less than 0.01), associated with a 20% decrease in LH pulse frequency (95% CI -71% to +31%, P = 0.37). There was a nonsignificant increase in follicle-stimulating hormone (FSH) pulse amplitude (2%, 95% CI -9% to +14%, P = 0.68) and in FSH pulse frequency (27%, 95% CI -4% to +58%, P = 0.08). The 22% decrease in the mean LH level (95% CI -85% to +12%, P = 0.13) and the 20% decrease in the mean FSH level (95% CI -53% to +37%, P = 0.33) were also not significant. CONCLUSIONS: The increase in LH pulse amplitude represents a direct effect of danazol on the hypothalamic-pituitary axis. PMID- 1902420 TI - Treatment of uterine leiomyomata with a luteinizing hormone-releasing hormone agonist: the possibility of nonsurgical management in selected perimenopausal women. AB - OBJECTIVE: To evaluate the efficacy of luteinizing hormone-releasing hormone agonist (LH-RH-a) in the treatment of leiomyomata. DESIGN: A retrospective randomized trial. SETTING: Hospital department of obstetrics and gynecology. PATIENTS: Twenty-five women, ages 36 to 54 years with symptomatic uterine leiomyomata, were divided into two groups according to the responsiveness to LH RH-a: group A patients reached menopause after LH-RH-a, whereas resumption of menstruation occurred within 12 weeks after cessation of therapy in group B. INTERVENTIONS: Luteinizing hormone-releasing hormone agonist was administered intranasally three times a day with 150 micrograms insufflation of one spray in each nostril (total dose: 900 micrograms/d). MAIN OUTCOME MEASURES: Efficacies of treatment were assessed in terms of uterine volume, hemoglobin concentrations, serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2), and bone density during and after treatment. RESULTS: In both groups, hemoglobin concentrations increased significantly after 16 weeks of treatment. A significant reduction in uterine volume was observed in both groups. After completing therapy, there was no further significant change in uterine volume in group A, whereas uterine volume in group B returned to pretreatment values. Serum LH and FSH concentrations were suppressed during treatment, but those gonadotropins in group A increased significantly up to the menopausal levels after treatment. Serum E2 concentrations in both groups showed consistent suppression by the end of the first treatment cycle. After cessation of therapy, serum E2 levels on group A remained in the castrate range, whereas E2 in group B returned to pretreatment levels, concomitant with the return of normal ovulation. CONCLUSIONS: Intranasal administration of LH-RH-a was successful in significantly decreasing uterine volume and increasing hemoglobin concentration in premenopausal women with leiomyomata. PMID- 1902421 TI - Gonadotropin-releasing hormone agonist improves the efficiency of controlled ovarian hyperstimulation/intrauterine insemination. AB - OBJECTIVE: Leuprolide acetate (LA) has improved the efficiency of human menopausal gonadotropins (hMG) in in vitro fertilization cycles. We hypothesized that the combination of LA/hMG/intrauterine insemination (IUI) would be more efficacious than hMG/IUI cycles. DESIGN: During an 18-month period, all patients completing either a hMG/IUI cycle (group I) or a LA/hMG/IUI cycle (group II) had the characteristics and outcomes of their stimulation cycles assessed. The groups were not prospectively randomized. SETTING: Referral center at a tertiary care hospital. PATIENTS: One hundred twenty three patients in group I completed 219 cycles, and 64 patients in group II completed 102 cycles. Twenty-eight of the patients who failed to conceive with hMG/IUI were advanced to group II. MAIN OUTCOME MEASURES: Pregnancy/IUI is compared between the two groups. RESULTS: Group II demonstrated significantly greater clinical pregnancy/IUI than group I (26.5% and 16.0%, respectively, P less than 0.05), as well as a higher live birth/IUI (21.6% and 12.8%, respectively, P less than 0.05). No difference was present in the rate of fetal wastage or multiple births. CONCLUSIONS: In our patients with recalcitrant infertility, the addition of a gonadotropin-releasing hormone agonist to hMG/IUI improved the pregnancy rate, without increasing the rate of multiple births or fetal wastage. PMID- 1902422 TI - In vitro fertilization as a diagnostic and therapeutic tool in a patient with partial 17,20-desmolase deficiency. AB - OBJECTIVE: To present a case with 17,20-desmolase activity deficiency in which in vitro fertilization (IVF) served not only as a therapeutic approach but also as a diagnostic tool for the specificity of the enzymatic deficiency. DESIGN: IVF in the patient under study compared with a control group. All women treated with pure follicle-stimulating hormone (FSH). SETTING: IVF program at the Instituto Valenciano de Infertilidad. PATIENTS, PARTICIPANTS: A patient with primary amenorrhea, who was the subject under study, and seven normally cycling control patients undergoing IVF in the same series. INTERVENTIONS: IVF, steroidogenesis in vitro of granulosa-luteal cell obtained at ovum pick-up. MAIN OUTCOME MEASURE(S): Oocyte fertilization and embryo cleavage. Serum and follicular fluid (FF) levels of estradiol (E2), progesterone (P), testosterone (T), androstendione (A), 17 alpha-hydroxyprogesterone (17-OHP). In vitro accumulation of E2 and P. RESULTS: Ovulation induction with FSH was successful in achieving follicular development despite low circulating E2. Fertilization and cleavage rates were similar to the control subjects. The patient developed ovarian hyperstimulation. The lack of 17,20-desmolase activity was detected by normal P levels in serum and FF, high 17-OHP, and low T, A, and E2 levels in serum and FF. Granulosaluteal cell cultures in the presence of T restored normal E2 and P production in response to gonadotropins. CONCLUSIONS: In patients with 17,20-desmolase deficiency, follicular development, oocyte maturation, and fertilization can take place in a low estrogenic environment. PMID- 1902423 TI - The ICU fellowship: an innovative orientation program for new graduates in critical care. PMID- 1902424 TI - Isolation and chemical study of the glycosaminoglycans from squid cornea. AB - 1. Oversulphated chondroitin sulphate (ca 93% of tissue glycosaminoglycans) with average molecular weight 72,500, chondroitin sulphate (5%) and small amounts of lowsulphated chondroitin sulphate were isolated from squid cornea. 2. The sulphation pattern of oversulphated chondroitin sulphate was delta di-4S (52%), delta di-diSD (28%), delta di-6S (9%) and delta di-OSCS (11%) and that of chondroitin sulphate 49, 1, 20 and 30% respectively. 3. All glycosaminoglycans contained neutral monosaccharides, glucose being the predominant neutral monosaccharide in oversulphated chondroitin sulphate and chondroitin sulphate and fucose in low-sulphated chondroitin sulphate. 4. Although L-iduronic acid was not detected, the digestion of oversulphated chondroitin sulphate with chondroitinases ABC and AC gave unexpected results. PMID- 1902425 TI - Some thoughts on the mechanism of action of insulin. AB - Proposed mechanisms by which insulin exerts its effects are discussed. Evidence for a role for the tyrosine kinase activity of the insulin receptor and of a phosphorylation/dephosphorylation cascade is presented. The possible roles of phospholipid breakdown, diacylglycerol, and protein kinase C are discussed. The hypothesis that insulin elicits the hydrolysis of a glycosyl phosphatidylinositol to form a mediator of certain of its actions is considered in detail. The evidence that a G protein is involved in insulin action is analyzed. PMID- 1902426 TI - Reduction of glomerular hyperfiltration in normoalbuminuric IDDM patients by 6 mo of aldose reductase inhibition. AB - Hyperglycemia causes enhanced glucose metabolism by the polyol pathway in tissues not requiring insulin for glucose uptake. It has been suggested that the high level of aldose reductase activity may cause functional and structural abnormalities in diabetes and may be involved in the development of late complications. To elucidate the effect of an aldose reductase inhibitor (ponalrestat) on kidney function in uncomplicated insulin-dependent diabetes mellitus (IDDM), 20 normoalbuminuric IDDM patients were randomized to follow either 6 mo of treatment with ponalrestat (n = 11, mean +/- SD age 30 +/- 8 yr, diabetes duration 10 +/- 6 yr) or 6 mo of placebo (age 33 +/- 7 yr, diabetes duration 12 +/- 6 yr). The glomerular filtration rate (clearance of [125I]iothalamate) was significantly reduced from 140 +/- 18 to 129 +/- 10 ml.min 1.1.73 m-2, 2P = 0.02) in the ponalrestat-treated patients, whereas no change was seen after placebo (142 +/- 12 vs. 141 +/- 12 ml.min-1.1.73 m-2). The renal plasma flow (clearance of 131I-labeled hippuran), urinary albumin excretion rate (radioimmunoassay), fractional albumin clearance, and renal vascular resistance were unchanged in both groups. HbA1c showed a modest increase during ponalrestat (7.9 +/- 1.8 vs. 8.7 +/- 1.5%, 2P = 0.01) but was unchanged during placebo. No side effects of ponalrestat were observed. Thus, inhibition of aldose reductase may reduce the characteristic hyperfiltration in uncomplicated IDDM. PMID- 1902427 TI - Effects of sorbinil, dietary myo-inositol supplementation, and insulin on resolution of neuroaxonal dystrophy in mesenteric nerves of streptozocin-induced diabetic rats. AB - Previous studies indicate that experimental diabetic autonomic neuropathy can be largely prevented by initiating therapy at the onset of diabetes. More clinically relevant, however, is the ability of therapy to reverse established neuropathy produced by long-standing diabetes. We have examined the effect of selected therapies on established neuroaxonal dystrophy (NAD) in ileal mesenteric nerves, a rat model of diabetic autonomic neuropathy. Groups of 3-mo-old rats were made diabetic with streptozocin (STZ-D) and allowed to survive untreated for 5 mo, at which time they were begun on sorbinil, dietary myo-inositol, and daily insulin therapies or left untreated for an additional 2 or 4 mo. Ultrastructural evidence of NAD was demonstrated in ileal mesenteric nerves of rats with untreated 5-mo STZ-D and increased with the duration of diabetes. No lesions were demonstrated in control rats of any age. myo-Inositol or sorbinil administration failed to alter the severity of diabetes as measured by its metabolic indices. Institution of sorbinil or insulin treatment at 5 mo of diabetes prevented the increase in, but did not normalize, NAD at 7 or 9 mo. Dietary myo-inositol failed to significantly reverse established NAD or prevent its initial development. Morphometric examination of ileal mesenteric nerves demonstrated a decrease in the number of axons comprising each diabetic Schwann cell unit, suggestive of chronic cycles of axonal degeneration and regeneration. This parameter, clearly abnormal by 5 mo of diabetes, was not normalized by 2 or 4 mo of insulin, sorbinil, or myo-inositol treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1902428 TI - Effect of Zn2+ on the proteolytic inhibitory action of insulin and biguanide antihyperglycemic drugs. AB - The involvement of Zn2+ in the inhibitory action of insulin and phenformin on bulk proteolysis was studied in the Langendorff rat heart with a Zn(2+)-buffering perfusate (0.1 mM citrate, physiological complete amino acids and 0.2% albumin). Proteins were biosynthetically labeled in vitro for 10 min with [3H]leucine. Rapidly degraded proteins were eliminated during a 3-h preliminary degradation without insulin or added Zn2+ (2 mM nonradioactive leucine). Insulin (5 nM), the lysosomal inhibitor chloroquine (30 microM), and the biguanide antihyperglycemic agent phenformin (2 microns) each caused a sustained 35-40% inhibition of [3H]leucine release beginning within 1-2 min and reaching a maximum at 1-1.5 h. When these agents were combined, their simultaneous proteolytic inhibitory effects were not appreciably greater than the effect of chloroquine alone. Infusion of supraphysiological perfusate Zn2+ (greater than 15 microM) mimicked the inhibitory effect of insulin and chloroquine on lysosomal proteolysis. Infusion of supraphysiological Co2+, Mn2+, Fe2+, and Cr3+ (30 microM, 0.5 h) caused no change in proteolysis; however, 30 microM Cu2+ caused a slight inhibition. Presumptive chelation of the background (approximately 20 nM) Zn2+ by infusion of 3 microM CaNa2 EDTA caused no change in protein degradation over 1-2 h. The infusion of a physiological concentration of 1 or 5 microM Zn2+ (as ZnCl2) caused no change in protein degradation over 1-2 h. Biguanides are known to reversibly form a Zn2+ complex with affinity less than that of Zn2+ for EDTA. Prior infusion of 3 microM CaNa2 EDTA inactivated the proteolytic inhibitory effect of maximal (2 microM) phenformin over at least 1.25 h of concurrent infusion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1902429 TI - Adsorption to starch of a beta-galactosidase fusion protein containing the starch binding region of Aspergillus glucoamylase. AB - We have constructed and purified by affinity chromatography three beta galactosidase (beta Gal) fusion proteins (BSB133, BSBCD8, and BGA134) containing amino acid (aa) sequences from Aspergillus glucoamylase (GA). BSB133, containing the C-terminal 133 aa of GA (aa 484-616), adhered to native starch granules with a much higher affinity (Kad = 18 ml/g starch) than a beta Gal control (Kad = 0.9 ml/g starch). Two other fusion proteins, BSBCD8 and BGA134, similar in size to BSB133, adhered to starch with a relatively low affinity (Kad = 7 ml/g starch, and Kad = 4 ml/g starch, respectively). BSBCD8 differs from BSB133 by a truncation of 8 aa at the C terminus. BGA134 contains 134 aa from an overlapping region of GA (aa 380-513). These results confirm the presence of a strong starch binding region (SBR) included in the C-terminal 133 aa of GA and indicate that the SBR can confer starch-binding activity on a fusion protein produced in Escherichia coli. In the presence of crude soluble cell extracts, the fusion proteins adsorbed by native starch granules with an affinity similar to that of the purified enzymes. BSB133 that had been adsorbed by starch from crude extracts could be eluted at a high level of purity, similar to that achieved by affinity chromatography. These results suggest that it may be feasible to use native starch as an adsorbent for the recovery and purification of recombinant fusion proteins containing the SBR. Starch has many favorable qualities for this application: it is inexpensive, stable, nontoxic, and easy to recover by centrifugation. PMID- 1902430 TI - Overproduction and characterization of the uracil-DNA glycosylase inhibitor of bacteriophage PBS2. AB - A plasmid expression vector (pZWtac1) was constructed which allowed inducible overexpression of the uracil-DNA glycosylase (Ung) inhibitor (Ugi)-encoding gene (ugi) in Escherichia coli. In this plasmid, the ugi gene was under the control of both its own promoter and the tac promoter. Constitutive expression of the ugi was observed in the absence of isopropyl-beta-D-thiogalactopyranoside (IPTG). In the presence of 1 mM IPTG, the Ugi protein was overproduced to an approx. 16-fold higher level, and accounted for approx. 19% of the total soluble cellular proteins. Following high-level production in E. coli, the Ugi protein was purified to apparent homogeneity. Using E. coli Ung, we observed that Ugi inactivated the enzyme in a noncompetitive manner. Kinetic studies revealed a Ki value (0.14 microM) of approx. twelve-fold lower than Km value (1.7 microM) of glycosylase. Ugi did not act synergistically with free uracil to inhibit E. coli Ung suggesting that uracil and Ugi could share a similar mode of inhibition. PMID- 1902431 TI - The synaptophysin-encoding gene in rat and man is specifically transcribed in neuroendocrine cells. AB - Synaptophysin (SY) is an integral membrane protein of presynaptic small (30-80 nm) translucent vesicles also present in dispersed neuroendocrine cells. As the occurrence of this type of vesicle is specific for two major pathways of differentiation, the neuronal and neuroendocrine-epithelial information on the regulation of SY synthesis should contribute to an understanding of regulatory principles common to both pathways. Isolation and comparison of the complete rat and human single-copy genes showed that despite the difference in size (16 kb in rat vs. 13 kb in man) intron/exon boundaries are precisely conserved. Surprisingly, intron VI is located in the 3'-noncoding region in both species. The major transcriptional start point, as determined by primer extension and S1 nuclease protection analyses in rat pheochromocytoma-derived PC12 cells and rat brain, mapped to a site 27 nt 5' of the first methionine codon. Unexpectedly, the 5' upstream region is devoid of any TATA or CAAT boxes, but shows instead typical features of 'housekeeping' genes, i.e., G + C-rich islands and four Sp1-binding motifs. Using 'nuclear run-on' assays, we have identified examples in which SY synthesis is regulated at the transcriptional level. Reporter gene constructs showed that approx. 1.2 kb of the immediate upstream region contains promoter enhancer elements that were, however, insufficient to confer cell-type specific expression, whereas sequences farther upstream were able to suppress thymidine kinase promoter activity in a cell-type-dependent fashion. PMID- 1902432 TI - Isolation and characterization of human pro-urokinase and its mutants accumulated within the yeast secretory pathway. AB - Human pro-urokinase (pro-UK) and two pro-UK deletion mutants, one lacking the epidermal growth factor(EGF)-like domain, and the other lacking both the EGF-like domain and the kringle domain, were produced in Saccharomyces cerevisiae. This was done using the yeast GAL7 promoter and the prepeptide sequence of a fungal aspartic proteinase, Mucor pusillus rennin (MPR). Although biologically active and heavily glycosylated pro-UKs were secreted into the culture medium, the amounts were extremely small. On the other hand, large amounts of pro-UKs of a single-chain form were accumulated inside the cells, exceeding 3-4% of total cellular proteins. The intracellular pro-UKs were N-glycosylated, probably with a single core carbohydrate unit, and amino acid sequencing of their N termini revealed that the secretion signal of MPR was correctly processed. Biologically active pro-UKs were recovered in high yields by means of solubilization with 4.5 M guanidine.HCl and subsequent dialysis for refolding. The refolded yeast pro-UK was indistinguishable from human kidney-derived pro-UK in terms of specific enzymatic activity and its secondary structure, as determined by circular dichroism spectroscopy. PMID- 1902433 TI - Synthesis and secretion of a fibrinolytically active tissue-type plasminogen activator variant in Escherichia coli. AB - A gene encoding a variant (lacking amino acids 6-173) of human tissue-type plasminogen activator (t-PA), consisting only of the second kringle domain (K2) and the serine protease domain (P), was fused to a DNA segment coding for the signal peptide of staphylococcal protein A and a synthetic gene coding for a protein with ability to bind immunoglobulin G (IgG). The fusion protein which was synthesized in Escherichia coli and secreted into the growth medium, was found to be fibrinolytically active. Purification of the fusion protein was performed in a single step by affinity chromatography with immobilized IgG. Enzymatically active K2P was liberated from the fusion protein by cleavage at a unique Asn-Gly dipeptide sequence using hydroxylamine. These results demonstrate that a variant of human t-PA can be synthesized and secreted by E. coli as a fibrinolytically active fusion protein, which upon specific cleavage yields an active variant t-PA of the expected size. PMID- 1902434 TI - Cloning and expression in COS-1 cells of a full-length cDNA encoding human coagulation factor X. AB - A 1.5-kb cDNA (FX) encoding full-length human coagulation factor X was isolated from a human fetal liver cDNA library. The identity of the insert in a selected phage lambda clone was confirmed to be FX by nucleotide (nt) sequence analysis and restriction mapping. This FX cDNA clone contained 1467 bp of coding sequence, no 5'-untranslated sequence, a short 3'-untranslated sequence of 10 nt and a poly(A) tail at the 3'-end. The FX cDNA was inserted into a mammalian expression vector and transfected into COS-1 monkey kidney cells. Media from transfected cells showed evidence of factor X antigen and, following addition of Russel's viper venom factor X activator, enhanced amidolytic activity toward a synthetic peptide rho-nitroanilide substrate. Immunoprecipitation with an anti-factor X monoclonal antibody of [35S]methionine-labeled cell-conditioned media showed evidence of polypeptides of 74, 55, and 17 kDa, as determined by SDS-PAGE followed by autoradiography. Together, these results indicate that an active factor X can be successfully expressed in a recombinant DNA expression system. This approach will allow the systematic structure/function investigation of this important blood-clotting enzyme. PMID- 1902435 TI - Aluminum salts stimulate luminol-enhanced chemiluminescence production by human neutrophils. AB - Aluminum intoxication is currently thought to play a major role in the development of Alzheimer's disease and in certain pathologic manifestations seen during long-term hemodialysis and aging. The hypothesis that aluminum toxicity is mediated via an increased free radical production was tested by studying the effects of two aluminum and five other metallic compounds on the production of luminol-enhanced chemiluminescence (LECL) by human neutrophils. AlCl3, Al2(SO4)3 and FeCl3 were found to stimulate LECL production by human neutrophils whereas FeCl2, CuCl, CuCl2, AuCl3 were inactive. Metal chelators such as Desferal, EDTA and DETAPA suppressed aluminum-induced stimulation and depressed cell-dependent LECL below basal levels. Sodium azide and Cytochalasin B greatly depressed both basal and aluminum-induced stimulation of LECL production, suggesting that, in this system, most of this stimulation was due to myeloperoxidase. These results suggest that high tissue aluminum concentrations may induce cell-tissue lesions by stimulating local production or release of mediators of tissue damage. PMID- 1902436 TI - Future data needs for quality of care monitoring, DRG considerations, reimbursement and outcome measurement. AB - For nurses and vendors, the challenge to achieve a useful automated record involves becoming participants in the organizations defining the nursing component of the medical record. The development of systems that monitor costs, quality and access are means to better support nurses and other health professionals. PMID- 1902437 TI - Endothelium-dependent responses of cerebral blood vessels during chronic hypertension. AB - Acetylcholine produces less dilatation of pial arterioles in stroke-prone spontaneously hypertensive rats (SHRSP) than in normotensive (WKY) rats. Responses of cerebral vessels to acetylcholine and bradykinin appear to involve different mechanisms. Our first goal was to determine whether responses of pial arterioles to bradykinin are impaired in SHRSP. Diameter of pial arterioles (20 60 microns) was measured using intravital microscopy in WKY rats and SHRSP (9-12 months old). Superfusion of bradykinin (3 x 10(-7) M) dilated pial arterioles by 35 +/- 6% (mean +/- SEM) in WKY rats, but only 21 +/- 3% in SHRSP (p less than 0.05 versus WKY rats). Both nitric oxide (5 x 10(-7) M) and nitroglycerin (10(-5) M) produced similar vasodilatation in WKY rats and SHRSP. Our second goal was to determine whether alteration of postreceptor mechanisms contributes to impairment of endothelium-dependent cerebral vasodilatation in SHRSP. Calcium ionophore A23187 (10(-5) M) produced more vasodilatation in WKY rats than in SHRSP (32 +/- 8% versus 9 +/- 4%, p less than 0.05). Responses to A23187 (10(-5) M) were inhibited by indomethacin (46 +/- 13% versus 15 +/- 5%, p less than 0.05) in WKY rats, whereas responses to A23187 (10(-6) M) were potentiated modestly by indomethacin (-3 +/- 2% versus 4 +/- 2%, p less than 0.05) in SHRSP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1902439 TI - Comparison of urokinase and tissue plasminogen activator for thrombolysis in rats. AB - Microvascular thrombosis in free flap and replantation surgery may be amenable to thrombolytic therapy. A blinded, controlled, preliminary study in rats compared urokinase (UK) and tissue plasminogen activator (t-PA) on thrombolytic efficacy, systemic fibrinolytic effect, and reocclusion. Bilateral femoral vein clots were induced in 38 rats. Local infusion of UK, t-PA, or saline was performed. Fibrinogen levels were drawn from one group. A second group was evaluated for reocclusion up to one month. Ipsilateral lysis occurred for reocclusion up to one month. Ipsilateral lysis occurred in 10/12, 13/13, and 0/13 of the UK, t-PA, and saline groups, respectively, with no significant difference detected between the UK and t-PA groups. Contralateral clot lysis occurred in both the UK and t-PA groups. No significant differences in the fibrinogen levels was detected among the three groups. Reocclusion occurred only in the UK group. PMID- 1902438 TI - Intravitreal recombinant tissue plasminogen activator in the treatment of experimentally induced bacterial endophthalmitis. AB - Intravitreal injection of antibiotics has been shown to be effective in the treatment of bacterial endophthalmitis, but does not prevent the formation of fibrin. Recombinant tissue plasminogen activator (rTPA), a fibrinolytic agent, was evaluated in experimentally induced Staphylococcus aureus endophthalmitis in an animal model. Significant fibrinous reaction in the vitreous was present in three of six eyes treated with intravitreal injection of clindamycin and rTPA (50%) and in one of five eyes treated with clindamycin only (20%). Fibrin clot formation in the anterior chamber was present in two of six eyes treated with clindamycin and rTPA (33%) and not observed in the clindamycin treated eyes (0%). These findings suggest that rTPA does not play a beneficial role in the treatment of bacterial endophthalmitis in the presence of the vitreous. PMID- 1902440 TI - Identification of endogenous sugar-binding proteins in the accessory sex glands of NMRI mice. A histochemical and biochemical study. AB - In the present study we report on the histotopographical distribution of carbohydrate-binding proteins in the prostate and seminal vesicle of sexually mature NMRI mice using a panel of fluorescein-isothiocyanate labelled neoglycoproteins and asialoglycoproteins. Additionally, biochemical analysis using affinity chromatography and SDS-gel electrophoresis was performed to purify and characterize the respective proteins from the tissue. Our histochemical results clearly demonstrate the presence of endogenous receptors for the carbohydrate part of glycoconjugates in both glands. In the prostate a distinct staining was seen after incubation with melibiose-BSA-FTC, glucuronic acid-BSA FTC and asialofetuin-FTC (only in the ventral prostate). In the epithelium of the seminal vesicle a weak staining occurred after incubation with asialofetuin-FTC and maltose-FTC. In the stroma of both accessory sex glands a distinct binding of several (neo)glycoproteins specific for beta-galactoside-binding proteins was observed which could be attributed to a beta-galactoside-binding lectin. Indeed biochemical analysis ascertained presence of such a histochemically detectable activity. We assume that the carbohydrate-binding proteins of the stroma, which were obviously linked to the elastic fibers, could play a role in the organisation of the extracellular matrix in the interstitium of the glands. PMID- 1902441 TI - The evolution of allelic diversity at the primate major histocompatibility complex class II loci. AB - The evolutionary history of polymorphism at the DQ alpha, DQ beta, and DR beta loci appears to be quite distinct and reflects different genetic mechanisms and selection pressures for the different loci. Phylogenetic analysis of sequences from a variety of species allows the tentative reconstruction of the order of gene duplication and of allelic diversification. Some of the major allelic types or lineages appear to be very old (greater than 20 myr) and selection has acted to maintain these ancient allelic types as well as, in the case of the DR beta loci, to favor new variants generated by recombining beta-sheet and alpha-helix domains. Phylogenetic analysis can also reveal balancing selection at individual residues of the class II beta chains. The highest number of phylogenetically inferred changes attributed to balancing selection was found at beta-chain residues located in the ABS and at those residues implicated in disease susceptibility. For some residues, the number of different amino acids observed at individual polymorphic positions is highly restricted and the few tolerated residues are common to all primate species studied. This observation supports the view that these positions are subject to some form of balancing selection. PMID- 1902442 TI - High dose rate afterloading intracavitary therapy in carcinoma of the cervix. AB - From January 1984 through December 1986, 87 patients with previously untreated carcinoma of the cervix received external beam pelvic irradiation and high dose rate intracavitary therapy (HDRT). There were 18 Stage IIA patients, 39 Stage IIB, and 30 Stage IIIB. The median age was 60 years and the median follow-up time was 42 months for patients at risk. Radiotherapy consisted of external megavoltage irradiation to the whole pelvis (median dose 4600 cGy) combined with one (6 patients), two (51 patients), or three (30 patients) HDRT insertions. A high dose rate remote afterloading unit with 60Co sources was used to deliver the HDRT. The prescribed dose to point A was between 800 and 1000 cGy per treatment. The dose rate at point A initially was approximately 150 cGy/min and dropped to approximately 100 cGy/min during the duration of the study. Treatments with multiple fractions were given at weekly intervals. The overall actuarial survival at 5 years was 88% for Stage IIA, 64% for Stage IIB and 32% for Stage IIIB patients. Pelvic recurrence remained the major cause of failure. Grade III and IV late complications included proctitis and bowel obstruction in six patients each. We conclude that HDRT results are similar to those obtained with conventional low dose rate intracavitary systems. HDRT is cost effective and minimizes exposure to personnel. Several questions, such as the total number of insertions required, dose per HDRT insertion, and optimal HDRT insertion schedule remain unanswered and further experience is needed to better clarify these issues. PMID- 1902443 TI - Cervical stump carcinoma. AB - Although supracervical hysterectomy is becoming a vanishingly rare procedure, there are still many women with a retained cervical stump. We have reviewed 70 patients treated at the Radiation Oncology Center, Mallinckrodt Institute of Radiology for carcinoma of the cervical stump. The average time between the hysterectomy and the diagnosis of cancer in the stump was 26.6 years. The median age at diagnosis of 63.5 years is 8.5 years older than the median age at diagnosis of patients with cancer of the cervix with an intact uterus. Patients were treated with external beam radiation and/or intracavitary implants. Sixteen patients underwent surgery as well. The 5- and 10-year overall actuarial survival for all patients was 60% and 40%, respectively. The 5- and 10-year progression free survival for all patients was 77% and 70%, respectively. Ten-year progression-free survival by stage was: 0--100%, 1A--100%, 1B--79%, 2A--100%, 2B- 66%, and 3B--39%. Poor histologic differentiation correlated with a decreased long-term progression-free survival. Black patients, and those receiving prolonged courses of external beam irradiation, had a trend toward a worse prognosis. Neither non-squamous histology nor gross appearance affected outcome. With a median follow-up time of 12.9 years, there were only three isolated local failures and four combined with distant metastases. Complications were few, with twice as many occurring in the gastrointestinal system as in the genitourinary tract. We conclude that carcinoma of the cervical stump effectively treated by radiation therapy yields results equivalent to those seen in patients with an intact uterus. PMID- 1902444 TI - Efficacy of i.v. or i.p. injected cytotoxic drugs on proliferating and non proliferating hair follicles of the mouse. AB - A range of drug doses of Adriamycin (ADR), Actinomycin-D (ACT-D), and Mitomycin-C (MMC) were given i.v. or i.p. to mice 1 day after a priming dose of radiation to elicit epilation response. The hair follicles were stimulated through plucking 11 days before irradiation or were unstimulated to represent proliferating and nonproliferating populations. The maximum epilation that appears at 8 days or at 8.5 weeks for proliferating and nonproliferating follicles was quantified using a subjective scale. In general, the i.v. route of administration was more effective than i.p. for all three drugs. Proliferating follicles were more susceptible than non-proliferating follicles to the action of drugs, especially ADR (p = .0001). Radiation doses which would give the same effect as ADR were calculated for proliferating follicles: 8 mg/kg given i.v. was equivalent to 4.6 (3.9, 5.2) Gy. For i.p. administration, 8 mg/kg was equivalent to only 0.6 (-0.1, 1.3) Gy. The in vivo assay of drug effect on hair follicles has advantages over LD10 as a model for toxicological investigation of new drugs: it can assess response of proliferating or non-proliferating cells of the same histotype and, in the case of proliferating follicles, it is quicker, thus enabling the use of doses higher than LD50 for bone marrow deaths. PMID- 1902445 TI - Production and effect of infectious Dane particles in transgenic mice. AB - We have demonstrated by immunoelectron microscopy that 42-nm particles with double-shelled structures characteristic of Dane particles are present in the serum of transgenic mice, 1.2HB-BS 10, carrying partly duplicated hepatitis B virus (HBV) genome. Furthermore, these particles were shown to infect primary human fetal hepatocytes as demonstrated by the elevation of HBV surface antigen (HBsAg) in the culture medium. HBV DNA is known to be expressed in a liver- and kidney-specific manner in the adult mouse, so we examined the developmental expression of viral antigens. In the liver, viral antigens (HBsAg and HBV e antigen) began to be expressed before birth and the level of expression showed a sharp rise after birth. On the other hand, in the kidney, viral antigens began to be expressed after birth. Serum levels of viral antigens were roughly proportional to the levels of expression in the liver, suggesting that the liver is the main source for viral antigens in the serum. None of these transgenic mice produced anti-HBs or anti-HBV core response or showed biochemical or pathological change up to at least 24 months of age. All these results suggest that infectious viral particles can be produced in transgenic mice, and that expression and replication of HBV DNA are not toxic in vivo. PMID- 1902446 TI - Verification of HTLV-I infection in the Solomon Islands by virus isolation and gene amplification. AB - We report the detection of human T-lymphotropic virus type I (HTLV-I) genomic sequences by polymerase chain reaction in lymphocyte cultures of three unrelated native Solomon Islanders, including a patient with HTLV-I myeloneuropathy, residing in widely separated regions. In addition, we have isolated HTLV-I from T cell lines derived from two of these individuals. Virus-specific proteins of 15, 19, 24, 46 and 53 kilodaltons were detected by immunofluorescence and Western immunoblot, using serum from a Colombian patient with HTLV-I myeloneuropathy, sera from HTLV-I-infected rabbits, and monoclonal and polyclonal antibodies against HTLV-I gag and env gene products. Amplification of HTLV-I gag, pol and env sequences by polymerase chain reaction confirmed that the viral isolates were HTLV-I, not HTLV-II. Our data clearly demonstrate that HTLV-I does exist in Melanesia. Although the Solomon Islands viral isolates resemble prototype strains of HTLV-I, we believe they represent variants of HTLV-I, particularly in the light of our recent isolation of an HTLV-I variant from Papua New Guinea. Nucleotide sequence analysis of these viral strains, now in progress, should clarify the molecular epidemiology and phylogeny of HTLV-I. PMID- 1902447 TI - Macrophage-T cell interaction is essential for the induction of p75 interleukin 2 (IL-2) receptor and IL-2 responsiveness in human CD4+ T cells. AB - Fresh human CD8+ T cells showed a strong proliferative response to a high concentration of interleukin 2 (IL-2) in the absence of macrophages. In contrast, CD4+ T cells revealed no significant IL-2 responsiveness in the absence of macrophages. However, if CD4+ T cells were cocultured with macrophages, they showed higher proliferative response to IL-2 than CD8+ T cells. In accordance with the magnitude of IL-2 responsiveness, freshly isolated CD8+ T cells expressed significant amounts of p75 IL-2 receptor, while fresh CD4+ T cells did not express p75 IL-2 receptor. The expression of p75 IL-2 receptor on CD4+ T cells was induced by coculture with macrophages. The macrophage-induced p75 IL-2 receptor acquisition was blocked by monoclonal antibody (mAb) against class II antigen. Moreover, the addition of anti-CD4 mAb or anti-class II mAb to the culture caused a great inhibition of IL-2 responsiveness of CD4+ T cells. These results strongly suggest that macrophage-T cell interaction through CD4 and/or class II molecules is essential for the expression of p75 IL-2 receptor and IL-2 responsiveness in human CD4+, but not CD8+ T cells. PMID- 1902448 TI - Antigen-presenting cells constitutively bind tumor antigens in the tumor-bearing state in vivo to construct an effective immunogenic unit. AB - Antigen-presenting cells (APC) constitutively process endogenous (self) proteins to bind the processed peptides to Ia molecules. In the present study, we investigated whether the same associative recognition also holds true for tumor associated antigens (TAA) that are regarded as "self" molecules in tumor-bearing hosts. The following results were obtained: (i) an APC-depleted splenic T cell population from CSA1M tumor-immunized hosts was stimulated to produce interleukin 2 in vitro when co-cultured with APC from CSA1M-bearing mice, but not from normal mice; and (ii) a Thy-1+ cell-depleted APC population from CSA1M-bearing mice could produce CSA1M tumor-specific protection in vivo when inoculated into naive syngeneic mice. These results provide evidence for the functional binding in vivo of TAA to APC in the tumor-bearing state. The results are discussed in the context of the paradox that tumor-bearers fail to reject their own malignancy despite the formation on APC of an effective immunogenic unit which is capable of stimulating tumor-specific T cells. PMID- 1902449 TI - Lung cancer risk among exsmokers. AB - Lung cancer risk among exsmokers according to years since cessation of smoking was assessed by means of a case-control study. The case series consisted of 1,052 lung cancer patients who were newly diagnosed and admitted to eight hospitals in Osaka in 1986-88. Smoking histories were compared with those of 1,111 controls admitted to the same hospitals during the same period without any diagnosis of smoking-related disease. The odds ratio of lung cancer for exsmokers compared to current smokers was estimated to be 0.90, 0.50, 0.51, 0.59, 0.48 and 0.29, for 1 4, 5-9, 10-14, 15-19, 20-24 and greater than or equal to 25 years after cessation of smoking, respectively. Risk reduction appeared to be greater for those who smoked less than the 1200 cigarette index, compared to those who smoked more. In classification according to histologic type, small cell and large cell carcinoma showed a rapid decrease compared to adenocarcinoma, while squamous cell carcinoma showed an intermediate pattern. Quantitative estimates for reduction of lung cancer risk among exsmokers can be used for projecting lung cancer incidence in the future, by assuming future trends of smoking prevalence, as well as for health education among individual smokers. PMID- 1902450 TI - Protective effect by potassium chloride against gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in spontaneously hypertensive rats. AB - The effects of oral potassium supplementation on the enhanced induction of gastric carcinogenesis by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in spontaneously hypertensive rats (SHR), and the norepinephrine concentration in their gastric wall were investigated. The SHR and normotensive Wistar Kyoto rats (WKY) as controls were given a solution of the carcinogen for 25 weeks and then 1% KCl solution or tap water to drink. In Week 52, the incidence of gastric cancers and their number per rat and the norepinephrine concentration in the gastric wall were significantly greater in SHR than in WKY. Prolonged oral treatment of SHR with potassium significantly reduced the incidence of gastric cancers and their number per rat, as well as the blood pressure and the norepinephrine concentration in the antral portion of the gastric wall. These findings indicate that prolonged treatment with KCl attenuated the enhancement of gastric carcinogenesis by MNNG in SHR. PMID- 1902451 TI - Age-dependent induction of preneoplastic liver cell foci by 2 acetylaminofluorene, phenobarbital and acetaminophen in F344 rats initially treated with diethylnitrosamine. AB - Effects of age on the induction of glutathione S-transferase placental form (GST P)-positive hepatic foci in rats were examined using a medium-term liver bioassay system (for carcinogens). F344 male rats aged 6, 26 and 46 weeks were initially given a single intraperitoneal injection of diethylnitrosamine (DEN, 200 mg/kg) and, beginning 2 weeks later, received 0.02% 2-acetylaminofluorene (2-AAF), 0.05% phenobarbital (PB) or 1.3% acetaminophen (AAP) in the diet for 6 weeks. All animals were subjected to two-thirds hepatectomy 3 weeks after the DEN injection and were killed at week 8. Quantitative analysis of GST-P-positive foci revealed significantly (P less than 0.001) increased induction over control levels in terms of both numbers and areas for 2-AAF at all ages (6, 26 and 46 weeks), but especially in the 6-week-old case. In the PB- and AAP-treated groups, the respective enhancing and inhibitory influences were most pronounced in the animals aged 6 weeks, and were less marked in older rats. Thus, the response of F344 rats to the modifying effects of chemicals was age-dependent, the conclusion being drawn that young rats are more susceptible and therefore more appropriate for assessment of carcinogenic, promoting and inhibitory effects of chemicals. PMID- 1902453 TI - Proliferative activity of human tumors: assessment using bromodeoxyuridine and flow cytometry. AB - Cell kinetics of human carcinoma xenografts and human solid tumors were evaluated by means of two-color flow cytometry using single sampling at appropriate time intervals after bromodeoxyuridine (BrdU) labeling. The tumors were resected several hours after the administration of BrdU, and flow cytometry was used to measure the DNA content and BrdU incorporation. Once the BrdU labeling index (LI) and DNA synthesis time (Ts) were obtained, the potential doubling time (Tpot) was calculated from these values. In 11 xenografts, the cell kinetic data were compared with the actual tumor doubling time (Td), and a good correlation between Tpot and Td was obtained (r = 0.91, P less than 0.005). In a clinical study, 33 patients with gastric cancer, colorectal cancer, lung cancer, or other solid tumors were analyzed. Aneuploid tumors had a significantly higher LI value (P less than 0.01) and a shorter Tpot than diploid tumors. The cell loss rate of human tumors ranged from 40% to 80%. These cell kinetic parameters therefore accurately indicated the level of proliferative activity of human tumors. PMID- 1902452 TI - Point mutation of c-Ki-ras oncogene in gastric adenoma and adenocarcinoma with tubular differentiation. AB - The presence of point mutation at codons 12, 13 and 61 of the c-Ki-ras oncogene was investigated in 7 cases of gastric adenoma and 35 cases of gastric adenocarcinoma using DNA samples from formalin-fixed and paraffin-embedded tissues. Oligonucleotides encompassing the three codons were amplified by using the polymerase chain reaction (PCR), and then examined for point mutation by the selective oligonucleotide hybridization technique. Point mutation was detected in three of the 7 adenomas (43%) and three of the 35 carcinomas (9%). All the gastric adenomas showed the histology of tubular adenoma, being very similar to that of colonic adenoma. The 35 cases of gastric adenocarcinoma were classified into 17 cases of differentiated type and 18 cases of undifferentiated type including signet-ring cell carcinoma. The point mutation of c-Ki-ras oncogene was detected only in the differentiated type (3/17, 18%), and there was no case with point mutation in the undifferentiated type. These results suggest that the genetic mechanism of carcinogenesis differs between the differentiated type and the undifferentiated type of gastric adenocarcinoma, and also that c-Ki-ras activation is possibly involved in a relatively early step of the "adenoma carcinoma sequence," which leads to the development of a portion of differentiated adenocarcinomas in the stomach. PMID- 1902454 TI - Ventilatory dysfunction precedes pulmonary vascular changes in monocrotaline treated rats. AB - Rats with established monocrotaline (MCT)-induced pulmonary hypertension also exhibit a profound increase in lung resistance (RL) and a decrease in lung compliance. Because airway/lung dysfunction could precede and influence the evolution of MCT-induced pulmonary vascular disease, it is important to establish the temporal relationship between development of pulmonary hypertension and altered ventilatory function in MCT-treated rats. To resolve this issue, we segregated 47 young Sprague-Dawley rats into four groups: control (n = 13), MCT1 (n = 9), MCT2 (n = 11), and MCT3 (n = 14). Each MCT rat received a single subcutaneous injection of MCT (60 mg/kg) 1 MCT1), 2 (MCT2), or 3 (MCT3) wk before the functional study. At 1 wk after MCT, significant increases in RL and alveolar wall thickness were observed, as was a significant decrease in carbon monoxide diffusing capacity (DLCO). Medial thickness of pulmonary arteries (50-100 microns OD) and right ventricular hypertrophy were not observed until 2 and 3 wk post MCT, respectively. Coincident with the right ventricular hypertrophy at 3 wk post MCT were decreased DLCO and increased alveolar wall thickness and lung dry weight. Pressure-volume curves of air-filled and saline-filled lungs showed marked rightward shifts during the 1st and 2nd wk after MCT administration and then decreased at the 3rd wk. These data suggest that MCT-induced alterations in airway/lung function preceded those of pulmonary vasculature and, therefore, implicate airway/lung dysfunctions as potentially contributing to the later development of pulmonary vascular abnormalities. PMID- 1902455 TI - Evidence for hypoxic depression of CO2-ventilation response in carotid body resected humans. AB - Steady-state CO2-ventilation response curves with hyperoxia (end-tidal PO2 greater than 200 Torr) and mild hypoxia (end-tidal PO2 approximately equal to 60 Torr) were compared in five carotid body-resected (BR) patients and five control patients. The data were analyzed by fitting a linear equation, V = S(PETCO2-B), where V is minute ventilation S is the response curve slope. PETCO2 is end-tidal PCO2, and B is the response curve threshold. S slightly increased from hyperoxia to hypoxia in both BR and control groups. On the other hand, B moderately increased with hypoxia in BR patients, whereas it slightly decreased in controls. These changes were all not significant. However, in accordance with the change in B, the response curve to hypoxia at V of 10 1/min was significantly shifted in opposite directions in the two groups, i.e., rightward and leftward shift in BR and control groups, respectively. Thus the average magnitude of V calculated at PETCO2 of 40 Torr in hypoxia was significantly lower in BR patients than in controls (P less than 0.01). We conclude that this hypoxic depression of the CO2 ventilation response found in BR patients may have resulted, at least in part, from modulation of the brain stem neural mechanisms that were elicited by loss of afferent discharges from the carotid body. PMID- 1902456 TI - Calcium channel blockers modulate airway constriction in the canine lung periphery. AB - We studied the effect of two voltage-sensitive calcium channel blockers on Na2EDTA-induced bronchoconstriction in the canine lung periphery. A wedged bronchoscope technique was used to measure collateral system resistance before and after challenges with aerosolized Na2EDTA, hypocapnia, aerosolized acetylcholine, and increased flow of dry air in anesthetized mongrel dogs. Nifedipine, a dihydropyridine calcium channel blocker, reduced hypocapnia-induced bronchoconstriction by 88 +/- 6% (SE) but did not alter Na2EDTA-induced constriction. Verapamil, a phenylalkylamine calcium channel blocker, attenuated hypocapnia- and Na2EDTA-induced bronchoconstriction by 69 +/- 6 and 44 +/- 7%, respectively, but did not significantly alter responses to either acetylcholine or dry air challenge. We conclude that calcium influx through voltage-sensitive calcium channels, perhaps of the T subtype, has a limited role in the initiation of Na2EDTA-induced bronchoconstriction in the canine lung periphery. PMID- 1902457 TI - Effect of increased inspired CO2 on respiratory dead space in ponies. AB - The objective of the present study was to determine the effect of elevated inspired CO2 on respiratory dead space (VD) of 12 normal, 8 carotid body denervated (CBD), 7 hilar nerve-denervated (HND), and 6 CBD+HND ponies. The Fowler technique was used to determine VD on a breath-by-breath basis while the ponies breathed room air and inspired CO2 at 3 and 6%. During room air breathing, tidal volume (VT) and VD were greater in HND ponies than in normal and CBD ponies (P less than 0.05), and VT was less and VD/VT was greater after CBD than before CBD. For all groups. VD, VT, and breathing frequency (f) increased and VD/VT decreased significantly (P less than 0.01) with increasing inspired CO2. During CO2 breathing, VT and VD were higher (P less than 0.05) in the HND ponies than in all other groups, the decrease (P less than 0.05) in VD/VT was greatest in the CBD+HND group, and f was lower in the HND and HND+CBD than in the normal and CBD ponies. In addition, when inspired CO2 was increased from 0 to 6%, the decrease in VD/VT was greater and the increase in arterial PCO2 was less (P less than 0.05) after CBD than before CBD. For 70% of the ponies in all groups, VD increased linearly with increases in VT; for most of the remainder, VD tended to plateau at higher values of VT. PMID- 1902458 TI - Hyperoxia prevents hypoxia-induced bronchial hyperreactivity via a cyclooxygenase independent mechanism. AB - We tested the hypothesis that prior exposure to alveolar hyperoxia prevents the hypoxia-induced enhancement of bronchial reactivity, possibly via a cyclooxygenase-dependent mechanism. In 15 sheep, specific lung resistance (sRL) was measured before and after 30 min of exposure to either air or a hypoxic gas mixture (13% O2). The sheep then inhaled 50 breaths of aerosolized 5% histamine solution (n = 9) or 10 breaths of 2.5% carbachol solution (n = 9), and measurements of sRL were repeated. On subsequent days the above protocols were repeated after a 30-min exposure to hyperoxia (O2 greater than or equal to 95%), without or after pretreatment with indomethacin (2 mg/kg). After air-sham exposure, carbachol and histamine increased mean sRL to 370 +/- 40 (SE) and 309 +/- 65% of baseline, respectively. Exposure to the hypoxic gas mixture had no effect on baseline sRL but enhanced the airway responsiveness to carbachol and histamine; mean sRL increased to 740 +/- 104 and 544 +/- 76% of baseline, respectively (P less than 0.05). Prior 30-min exposure to hyperoxia prevented the hypoxia-induced enhancement of bronchial reactivity to carbachol (sRL = 416 +/- 66% of baseline) and histamine (sRL = 292 +/- 41% of baseline) without affecting the airway responsiveness to these agents after air. Pretreatment with indomethacin did not reverse the protective effects of hyperoxia or the hypoxia induced enhancement of bronchial reactivity. We conclude that 1) prior exposure to alveolar hyperoxia prevents the hypoxia-induced enhancement of bronchial reactivity and 2) neither the protective effects of hyperoxia nor the hypoxia induced enhancement of bronchial reactivity is mediated via a cyclooxygenase dependent mechanism. PMID- 1902459 TI - Alveolar gas composition and exchange during deep breath-hold diving and dry breath holds in elite divers. AB - End tidal O2 and CO2 (PETCO2) pressures, expired volume, blood lactate concentration ([Lab]), and arterial blood O2 saturation [dry breath holds (BHs) only] were assessed in three elite breath-hold divers (ED) before and after deep dives and BH and in nine control subjects (C; BH only). After the dives (depth 40 70 m, duration 88-151 s), end-tidal O2 pressure decreased from approximately 140 Torr to a minimum of 30.6 Torr, PETCO2 increased from approximately 25 Torr to a maximum of 47.0 Torr, and expired volume (BTPS) ranged from 1.32 to 2.86 liters. Pulmonary O2 exchange was 455-1,006 ml. CO2 output approached zero. [Lab] increased from approximately 1.2 mM to at most 6.46 mM. Estimated power output during dives was 513-929 ml O2/min, i.e. approximately 20-30% of maximal O2 consumption. During BH, alveolar PO2 decreased from approximately 130 to less than 30 Torr in ED and from 125 to 45 Torr in C. PETCO2 increased from approximately 30 to approximately 50 Torr in both ED and C. Contrary to C, pulmonary O2 exchange in ED was less than resting O2 consumption, whereas CO2 output approached zero in both groups. [Lab] was unchanged. Arterial blood O2 saturation decreased more in ED than in C. ED are characterized by increased anaerobic metabolism likely due to the existence of a diving reflex. PMID- 1902460 TI - Pulmonary vasodilation to endothelin isopeptides in vivo is mediated by potassium channel activation. AB - The present study was undertaken to investigate the effects of endothelin (ET) isopeptides on the pulmonary vascular bed of the intact spontaneously breathing cat under conditions of constant pulmonary blood flow and left atrial pressure. When pulmonary vasomotor tone was actively increased by intralobar infusion of U 46619, intralobar bolus injections of ET-1 (1 microgram), ET-2 (1 microgram), and ET-3 (3 micrograms) produced marked reductions in pulmonary and systemic vascular resistances. The pulmonary vasodilator response to each ET isopeptide was not altered by atropine (1 mg/kg iv), indomethacin (2.5 mg/kg iv), and ICI 118551 (1 mg/kg iv) but was significantly diminished by glybenclamide (5 mg/kg iv). This dose of glybenclamide significantly diminished the decrease in lobar arterial and systemic arterial pressures in response to intralobar injection of pinacidil (30 and 100 micrograms) and cromakalim (10 and 30 micrograms), whereas pulmonary vasodilator responses to acetylcholine (0.03 and 0.1 microgram), prostaglandin I2 (0.1 and 0.3 microgram), and isoproterenol (0.03 and 0.1 microgram) were not altered. The systemic vasodilator response to each ET isopeptide was not changed by glybenclamide or by the other blocking agents studied. The present data comprise the first publication demonstrating that ET-1, ET-2, and ET-3 dilate the pulmonary vascular bed in vivo. The present data further suggest that the pulmonary vasodilator response to ET isopeptides depends, in part, on activation of potassium channels and is mediated differently from the systemic vasodilator response to these substances. Contrary to earlier work, the present data indicate the pulmonary vascular response to ET isopeptides does depend on the preexisting level of pulmonary vasomotor tone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1902461 TI - Introduction of proteins into living bacterial cells: distribution of labeled HU protein in Escherichia coli. AB - Growing bacterial cells forming division septa have sites near the septa that are sensitive to EDTA shock. Cells treated with EDTA incorporate proteins and other molecules from the surrounding medium, probably via vesiclelike lesions at the septa that are induced by EDTA. The amount of protein taken up is proportional to the protein concentration in the permeabilization medium. Incorporated molecules equilibrate throughout the cytoplasm, and those with affinity for DNA bind to the nucleoid. Conditions that promote the viability of permeabilized cells and help to avoid otherwise irreversible effects of EDTA are defined. Procedures for selecting cells that have incorporated protein and for studying the distribution of the protein and its effects in growing-dividing cells are described. The procedure may have several applications to molecular and cellular biology; however, we describe here the localization in living cells of the histonelike protein HU. Fluorescence microscopy of cells containing different amounts of fluorescein-labeled HU (varied from approximately 10(3) to 10(5) molecules per cell) showed that the HU concentrates in the nucleoid and is uniformly distributed throughout this structure. Control experiments demonstrated that unlabeled interior parts of the nucleoid can be resolved when labeled proteins that do not bind DNA or enter the nucleoid are introduced into living cells. It was concluded that in vivo added HU binds primarily DNA and that there are no intrinsic restrictions on major regions of the nucleoid to which the added HU protein may bind. PMID- 1902463 TI - Genetic regulation of morphogenesis in Bacillus subtilis: roles of sigma E and sigma F in prespore engulfment. AB - Electron microscopic examination of sporulating cultures of wild-type Bacillus subtilis revealed that the morphological events previously characterized as stages II and III can be divided into four substages, namely, stages IIi, IIii, IIiii, and III. The ultrastructural phenotypes of several stage II mutant strains indicate that each of the four substages has a biochemical and genetic basis. Two of the genes needed for the transition from stage II to stage III encode transcription factors sigma E and sigma F. Their roles during spore morphogenesis have been the subject of much speculation. We now show that sigma E controls genes involved in the morphological transition from stage IIi to stage IIii and then stage IIiii, while the transition to stage III may be determined by genes controlled by sigma F. The results also indicate the existence of at least two undiscovered sporulation genes involved in B. subtilis spore morphogenesis. PMID- 1902462 TI - Cloning and sequence analysis of the LPD-glc structural gene of Pseudomonas putida. AB - Pseudomonas putida is able to produce three lipoamide dehydrogenases: (i) LPD glc, which is the E3 component of the pyruvate and 2-ketoglutarate dehydrogenase complexes and the L-factor for the glycine oxidation system; (ii) LPD-val, which is the specific E3 component of the branched-chain keto acid dehydrogenase complex and is induced by growth on leucine, isoleucine, or valine; and (iii) LPD 3, which was discovered in a lpdG mutant and whose role is unknown. Southern hybridization with an oligonucleotide probe encoding the highly conserved redox active site produced three bands corresponding to the genes encoding these three lipoamide dehydrogenases. The complete structural gene for LPD-glc, lpdG, was isolated, and its nucleotide sequence was determined. The latter consists of 476 codons plus a stop codon, TAA. The structural gene for LPD-glc is preceded by a partial open reading frame with strong similarity to the E2 component of 2 ketoglutarate dehydrogenase of Escherichia coli. This suggests that lpdG is part of the 2-ketoglutarate dehydrogenase operon. LPD-glc was expressed in Pseudomonas putida JS348 from pHP4 which contains a partial open reading frame corresponding to the E2 component, 94 bases of noncoding DNA, and the structural gene for lpdG. This result indicates that lpdG can be expressed separately from the other genes of the operon. PMID- 1902465 TI - Heat shock response of the archaebacterium Methanococcus voltae. AB - The general properties of the heat shock response of the archaebacterium Methanococcus voltae were characterized. The induction of 11 heat shock proteins, with apparent molecular weights ranging from 18,000 to 90,000, occurred optimally at 40 to 50 degrees C. Some of the heat shock proteins were preferentially enriched in either the soluble (cytoplasm) or particulate (membrane) fraction. Alternative stresses (ethanol, hydrogen peroxide, NaCl) stimulated the synthesis of subsets of the heat shock proteins as well as unique proteins. Western blot (immunoblot) analysis, in which antisera to Escherichia coli heat shock proteins (DnaK and GroEL) were used, did not detect any immunologically cross-reactive proteins. In addition, Southern blot analysis did not reveal any homology between M. voltae and four highly conserved heat shock genes, mopB and dnaK from E. coli and hsp70 genes from Drosophila species and Saccharomyces cerevisiae. PMID- 1902464 TI - Molecular cloning, nucleotide sequence, and characterization of the Bacillus subtilis gene encoding the DNA-binding protein HBsu. AB - A homologous class of histonelike proteins which are believed to wrap the DNA and to condense the chromosome into highly folded nucleoid structures has been identified in different bacterial species. Bacillus subtilis encodes a homodimeric DNA-binding protein called HBsu. We have cloned the corresponding gene (hbs) on a 3.8-kb fragment. The gene was subcloned to a 1-kb fragment, sequenced, and characterized. It encodes a 92-amino-acid protein with a predicted molecular mass of 9,884 Da. Fortunately, analysis of the DNA sequence downstream of the 3' end of hbs revealed the location of the first 19 amino acid residues of MtrA. This finding located the hbs gene unequivocally to the 5' end of the mtr operon at about 204 degrees on the standard genetic map of B. subtilis. Northern (RNA) blot analysis and primer extension studies indicated the presence of two distinct hbs transcripts, which were found to be initiated at two different sites located about 160 bases apart. Several attempts to replace the hbs gene in the B. subtilis chromosome with a cat-interrupted copy (hbs::cat) through marker replacement recombination were unsuccessful. In order to study whether hbs is an essential gene, we have constructed a strain containing a truncated copy of the gene behind its own promoter and another intact copy under control of the isopropyl-beta-D-thiogalactopyranoside (IPTG)-inducible spac-1 promoter. In this strain (BM19), normal growth was found to depend on IPTG, whereas in the absence of IPTG, growth was severely affected. These results suggest an essential role for the hbs gene product for normal growth in B. subtilis. PMID- 1902466 TI - Analysis of a Corynebacterium glutamicum hom gene coding for a feedback-resistant homoserine dehydrogenase. AB - From a Corynebacterium glutamicum mutant possessing a homoserine dehydrogenase resistant to feedback inhibition by L-threonine, the corresponding gene (homFBR) was analyzed and compared with the wild-type hom gene. DNA fragment exchange experiments between both genes showed that a 0.23-kb region close to the 3' terminus of homFBR was responsible for deregulation. Nucleotide sequence analysis revealed a single transition from G to A in homFBR leading to replacement of glycine-378 by glutamate in the mutant homoserine dehydrogenase. PMID- 1902467 TI - Transsulfuration in archaebacteria. AB - The transfer of sulfur from methionine to cysteine in the archaebacteria Sulfolobus acidocaldarius and Halobacterium marismortui was studied by feeding 34S-labeled methionine to cells and measuring the incorporation of 34S into protein-bound cellular cysteine and methionine by mass spectrometry. It was found that, as are eucaryotes, both of these archaebacteria were able to convert the sulfur of methionine to cysteine. PMID- 1902468 TI - Serine modulates substrate channeling in tryptophan synthase. A novel intersubunit triggering mechanism. AB - Tryptophan synthase, an alpha 2 beta 2 complex, is a classic example of an enzyme that is thought to "channel" a metabolic intermediate (indole) from the active site of the alpha subunit to the active site of the beta subunit. We now examine the kinetics of substrate channeling by tryptophan synthase directly by chemical quench-flow and stopped-flow methods. The conversion of indole-3-glycerol phosphate (IGP) to tryptophan at the active site proceeds at a rate of 24 s-1, which is limited by the rate of cleavage of IGP to produce indole (alpha reaction). In a single turnover experiment monitoring the conversion of radiolabeled IGP to tryptophan, only a trace of indole is detectable (less than or equal to 1% of the IGP), implying that the reaction of indole to form tryptophan must be quite fast (greater than or equal to 1000 s-1). The rate of reaction of indole from solution is much too slow (40 s-1 under identical conditions) to account for the negligible accumulation of indole in a single turnover. Therefore, the indole produced at the alpha site must be rapidly channeled to the beta site, where it reacts with serine to form tryptophan: channeling and the reaction of indole to form tryptophan must each occur at rates greater than or equal to 1000 s-1. Steady-state turnover is limited by the slow rate of tryptophan release (8 s-1). In the absence of serine, the cleavage of IGP to indole is limited by a change in protein conformation at a rate of 0.16 s-1. When the alpha beta reaction is initiated by mixing enzyme with IGP and serine simultaneously, there is a lag in the cleavage IGP and formation of tryptophan. The kinetics of the lag correspond to the rate of formation of the aminoacrylate in the reaction of serine with pyridoxal phosphate at the beta site, measured by stopped-flow methods (45 s-1). There is also a change in protein fluorescence, suggestive of a change in protein conformation, occurring at the same rate. Substitution of cysteine for serine leads to a longer lag in the kinetics of IGP cleavage and a correspondingly slower rate of formation of the aminoacrylate (6 s 1). Thus, the reaction of serine at the beta site modulates the alpha reaction such that the formation of the aminoacrylate leads to a change in protein conformation that is transmitted to the alpha site to enhance the rate of IGP cleavage 150-fold.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1902469 TI - Calcium binding to calmodulin and its globular domains. AB - The macroscopic Ca(2+)-binding constants of bovine calmodulin have been determined from titrations with Ca2+ in the presence of the chromophoric chelator 5,5'-Br2BAPTA in 0, 10, 25, 50, 100, and 150 mM KCl. Identical experiments have also been performed for tryptic fragments comprising the N-terminal and C terminal domains of calmodulin. These measurements indicate that the separated globular domains retain the Ca2+ binding properties that they have in the intact molecule. The Ca2+ affinity is 6-fold higher for the C-terminal domain than for the N-terminal domain. The salt effect on the free energy of binding two Ca2+ ions is 20 and 21 kJ. mol-1 for the N- and C-terminal domain, respectively, comparing 0 and 150 mM KCl. Positive cooperativity of Ca2+ binding is observed within each globular domain at all ionic strengths. No interaction is observed between the globular domains. In the N-terminal domain, the cooperativity amounts to 3 kJ.mol-1 at low ionic strength and greater than or equal to 10 kJ.mol-1 at 0.15 M KCl. For the C-terminal domain, the corresponding figures are 9 +/- 2 kJ.mol-1 and greater than or equal to 10 kJ.mol-1. Two-dimensional 1H NMR studies of the fragments show that potassium binding does not alter the protein conformation. PMID- 1902470 TI - Functional difference between intrinsic and extrinsic coagulation pathways. Kinetics of factor X activation on human monocytes and alveolar macrophages. AB - Activation of coagulation factor X via the intrinsic pathway requires the assembly of factors IXa and VIII on lipid membranes. It is known that the platelet expresses membrane sites for assembly of factors IXa/VIII and promotes efficient factor X activation. We now show that human blood monocytes, but not lymphocytes or polymorphonuclear leukocytes, also express appropriate sites for factors IXa/VIII assembly. The maximal rate of factor X activation by factors IXa (0.75 nM) and VIII (1 unit/ml) assembled on monocytes is similar to the maximal rate on platelets. This rate, adjusted per micromole of lipid phosphorus, is 1636 +/- 358 nM factor Xa/min on monocyte, and 1569 +/- 54 nM factor Xa/min on platelets. At physiologic concentrations of factors X and VIII, the activation rate increases with factor IXa concentration asymptotically approaching a maximum. Half-maximal rate is achieved with 1.0 +/- 0.16 nM factor IXa. Monocytes and macrophages, but not platelets, can express membrane tissue factor and thus promote simultaneous assembly of two distinct factor X-activating protease complexes. In these studies, blood monocytes and alveolar macrophages are used as membrane sources in kinetic experiments comparing factor X activation by intrinsic (factor IXa/VIII) versus extrinsic (factor VII/tissue factor) protease complexes. At plasma concentration of factors VIII and VII, apparent Km on the monocyte is 14.6 +/- 1.4 nM for intrinsic and 117.0 +/- 10.1 nM for extrinsic activation. The apparent Km on alveolar macrophages is 12.1 +/- 1.9 and 90.6 +/- 10.2 nM for intrinsic and extrinsic activation, respectively. Maximal rates on monocytes at saturating concentration of factors IXa, VIII, and VII are 48.0 +/- 11.2 nM factor Xa/min, for intrinsic activation, and 16.5 +/- 5.5 nM factor Xa/min, for extrinsic activation. These data show that the monocyte/macrophage is the only blood-derived cell type with membrane sites for both intrinsic and extrinsic pathway assembly. We have exploited this characteristic of the monocyte/macrophage membrane to demonstrate that factor X activation by the intrinsic pathway protease is more efficient than activation via the extrinsic pathway protease complex. PMID- 1902471 TI - Role of lysine 173 in heparin binding to heparin cofactor II. AB - Heparin cofactor II (HC) is a plasma serine proteinase inhibitor (serpin) that inhibits alpha-thrombin in a reaction that is dramatically enhanced by heparin and other glycosaminoglycans/polyanions. We investigated the glycosaminoglycan binding site in HC by: (i) chemical modification with pyridoxal 5'-phosphate (PLP) in the absence and presence of heparin and dermatan sulfate; (ii) molecular modeling; and (iii) site-directed oligonucleotide mutagenesis. Four lysyl residues (173, 252, 343, and 348) were protected from modification by heparin and to a lesser extent by dermatan sulfate. Heparin-protected PLPHC retained both heparin cofactor and dermatan sulfate cofactor activity while dermatan sulfate protected PLPHC retained some dermatan sulfate cofactor activity and little heparin cofactor activity. Molecular modeling studies revealed that Lys173 and Lys252 are within a region previously shown to contain residues involved in glycosaminoglycan binding. Lys343 and Lys348 are distant from this region, but protection by heparin and dermatan sulfate might result from a conformational change following glycosaminoglycan binding to the inhibitor. Site-directed mutagenesis of Lys173 and Lys343 was performed to further dissect the role of these two regions during HC-heparin and HC-dermatan sulfate interactions. The Lys343----Asn or Thr mutants had normal or only slightly reduced heparin or dermatan sulfate cofactor activity and eluted from heparin-Sepharose at the same ionic strength as native recombinant HC. However, the Lys173----Gln or Leu mutants had greatly reduced heparin cofactor activity and eluted from heparin Sepharose at a significantly lower ionic strength than native recombinant HC but retained normal dermatan sulfate cofactor activity. Our results demonstrate that Lys173 is involved in the interaction of HC with heparin but not with dermatan sulfate, whereas Lys343 is not critical for HC binding to either glycosaminoglycan. These data provide further evidence for the determinants required for glycosaminoglycan binding to HC. PMID- 1902472 TI - Myocardial triglyceride turnover and contribution to energy substrate utilization in isolated working rat hearts. AB - The objective of this study was to determine the contribution of myocardial triglycerides to overall ATP production in isolated working rat hearts. Endogenous lipid pools were initially prelabeled (pulsed) by perfusing hearts for 60 min with Krebs-Henseleit buffer containing 1.2 mM [1-14C]palmitate. During a subsequent 60-min period (chase), hearts were perfused with either no fat, low fat (0.4 mM [9,10-3H] palmitate), or high fat (1.2 mM [9,10-3H]palmitate). All buffers contained 11 mM glucose. During the "chase," 14CO2 production (a measure of endogenous fatty acid oxidation) and 3H2O production (a measure of exogenous fatty acid oxidation) were determined. Oxidative rates of endogenous fatty acids during the chase were 279 +/- 50, 88 +/- 14, and 88 +/- 8 nmol of [14C]palmitate oxidized per g dry weight.min in the no fat, low fat, and high fat groups, respectively, compared to exogenous palmitate oxidation rates of 0, 361 +/- 68, and 633 +/- 60 nmol of [3H]palmitate/g dry weight.min, in the no fat, low fat, and high fat groups, respectively. Endogenous [14C]palmitate oxidation rates were matched by loss of [14C]palmitate from endogenous myocardial triglycerides. Overall triglyceride content decreased during the no fat and low fat chase perfusion but did not change during the high fat chase. Loss of triglyceride [14C]palmitate during the high fat chase was matched by incorporation of exogenous [3H]palmitate in triglycerides. In a second series of perfusions, three groups of hearts were perfused under similar conditions, except that unlabeled palmitate was used during the "pulse" and that 11 mM [2-3H/U-14C]glucose and unlabeled palmitate was present during the chase. During the chase, both glycolysis (3H2O production) and glucose oxidation (14CO2 production) rates were measured. Rates of glucose oxidation were inversely related to the fatty acid concentration in the perfusate (1257 +/- 158, 366 +/- 40, and 124 +/- 26 nmol of glucose oxidized per min.g dry weight in the no fat, low fat, and high fat groups, respectively), while rates of glycolysis were not significantly different between these groups. Calculation of overall ATP production from both oxidative and glycolytic sources determined that even in the presence of high concentrations of fatty acids, myocardial triglyceride turnover can provide over 11% of steady state ATP production in the aerobically perfused heart. In the absence of fatty acids, myocardial triglyceride fatty acids can become the major energy substrate of the heart.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1902473 TI - Differential expression during development of ADP-ribosylation factors, 20-kDa guanine nucleotide-binding protein activators of cholera toxin. AB - Cholera toxin exerts its effects on cells in large part through the ADP ribosylation of guanine nucleotide-binding proteins. Toxin-catalyzed ADP ribosylation is enhanced by approximately 20-kDa guanine nucleotide-binding proteins termed ADP-ribosylation factors (ARFs), which are allosteric activators of the toxin catalytic unit. Rabbit antiserum against a purified bovine brain ARF (sARF II) reacted on immunoblots with two approximately 20-kDa ARF-like proteins (sARF I and II) in tissue extracts from bovine, rat, frog, and chicken. Levels of ARF were higher in brain than in non-neural tissues. In rat brain, on the second postnatal day, amounts of sARF I and II were similar. By the 10th postnatal day and thereafter, sARF II predominated. Relative levels of ARF determined by immunoreactivity were in agreement with levels assessed in functional assays of cholera toxin-catalyzed ADP-ribosylation. Based on nucleotide and deduced amino acid sequences of human and bovine cDNAs, there appear to be at least six different ARF-like genes. Northern blots of rat brain poly(A)+ RNA were hybridized with cDNA and oligonucleotide probes specific for each of the human and bovine ARF genes. From the second to the 27th postnatal day, ARF 3 mRNA increased, whereas mRNAs for ARFs 2 and 4 decreased; and those for ARFs 1, 5, and 6 were apparently unchanged. Partial amino acid sequence of sARF II is consistent with it being either the ARF 1 or 3 gene product. The developmental changes in rat brain ARF parallel neuronal maturation and synapse formation. PMID- 1902474 TI - Roles of the highly conserved aspartate and lysine residues in the response regulator of bacterial chemotaxis. AB - The chemotactic responses of bacteria such as Escherichia coli and Salmonella typhimurium are mediated by phosphorylation of the CheY protein. Phospho-CheY interacts with the flagellar motor switch to cause tumbly behavior. CheY belongs to a large family of phosphorylated response regulators that function in bacteria to control motility and regulate gene expression. Residues corresponding to Asp57, Asp13, and Lys109 in CheY are highly conserved among all of these proteins. The site of phosphorylation in CheY is Asp57, and in the three dimensional structure of CheY the Asp57 carboxylate side chain is in close proximity to the beta-carboxylate of Asp13 and the epsilon-amin of Lys109. To further examine the roles of these residues in response regulator function, each has been mutated to a conservative substitution. Asn for Asp and Arg for Lys. All mutations abolished CheY function in vivo. Whereas the Asp to Asn mutations dramatically reduced levels of CheY phosphorylation, the Lys to Arg mutation had the opposite effect. The high level of phosphorylation in the Lys109 mutant results from a decreased autophosphatase activity as well as a lack of phosphatase stimulation by the phosphatase activating protein, CheZ. Despite its high level of phosphorylation, the Lys109 mutant protein cannot produce tumbly behavior. Thus, Lys109 is required for an event subsequent to phosphorylation. We propose that an interaction between the epsilon-amino of Lys109 and the phosphoryl group at Asp57 is essential for the conformational switch that leads to activation of CheY. PMID- 1902475 TI - Epidermal growth factor and other mitogens induce binding of a protein complex to the c-fos serum response element in human astrocytoma and other cells. AB - Rapid stimulation of c-fos transcription by many agonists requires the serum response element (SRE), which binds at least two distinct nuclear proteins, p67SRF and p62TCF. Using nuclear protein extracts from 1321-N1 human astrocytoma cells, we investigated ligand-induced changes in binding of these proteins to SRE probes. In these cells c-fos mRNA expression can be induced by epidermal growth factor (EGF) through protein kinase C-independent pathways and by phorbol esters through protein kinase C. We detected two DNA-protein complexes that formed specifically with the SRE (bands 1 and 2). Band 2 formation was increased 4-6 min after stimulation with EGF as well as serum and phorbol esters; this peaked at 10 30 min and returned to basal levels by 60 min. Induction of band 2 formation preceded the onset and peak accumulation of c-fos mRNA (15 and 30 min after EGF stimulation, respectively) and its return to basal levels (by 1-2 h). Band 2 formation was also increased A431 cells stimulated with EGF and in HeLa and Swiss 3T3 cells stimulated with serum. We found that band 1 contained p67SRF bound to the SRE; band 2 contained p67SRF and a second protein. Gel shift analyses using [35S]methionine-labeled p67SRF and nonradioactive DNA probes suggested that hormone treatment most likely modified the second protein component of band 2. Transient transfection of 1321-N1 cells with plasmids containing point mutations that prevented band 2 formation in vitro also abolished induction of c-fos transcription in vivo as assayed by RNase protection analysis. Thus, hormone stimulated formation of the protein-DNA complex represented by band 2 may be involved in the activation of c-fos transcription. PMID- 1902476 TI - The isolation and partial characterization of a rat incisor dentin matrix polypeptide with in vitro chondrogenic activity. AB - In vivo implants of demineralized dentin matrix into muscle induce the formation of bone within the muscle. As with bone matrix implants, the bone induction appears to follow a chondrogenic pathway. Outgrowth cells from explants of neonatal rat muscle respond to bone matrix, in vitro, by expressing a heightened synthesis of sulfated proteoglycans and type II collagen, phenotypic of cartilage. The in vitro cell culture system has been used as an assay to monitor the isolation of the factor responsible for expression of this phenotypic transformation. Soluble proteins extracted from rat incisor dentin matrix during demineralization with EDTA, and not precipitable with 1.0 M CaCl2, were active in the in vitro system. The active extract was fractionated by Sephacryl S-100 chromatography in 6 M guanidine HCl, isoelectric focusing in Immobilines, and by reverse phase high performance liquid chromatography. All fractions were assayed for activity at every stage. The final active fraction from the reverse phase chromatography on a Zorbax Poly-F column was purified to homogeneity, and yielded a single spot on two-dimensional gel electrophoresis. The component, RP-4, had pI 5.4-5.5, and an apparent Mr 6,000-10,000, based on globular protein standards. Maximal activity with respect to both sulfate incorporation into proteoglycan and production of type II collagen was in the 1.0-10 ng/ml range. The RP-4 had a unique amino-terminal amino sequence and was rich in Gly, Pro, Glx, and Ala residues. It was different from transforming growth factor-beta and the bone morphogenetic protein family of proteins in these essential features. PMID- 1902477 TI - Fungal translocation is associated with increased mortality after thermal injury in guinea pigs. AB - Thermal injury increases the rate of translocation of Candida albicans in guinea pigs, but early enteral feeding can significantly decrease this rate. We studied the combined effects of C. albicans translocation and early feeding on outcome of thermal injury in guinea pigs. Eighty guinea pigs were subjected to a flame burn covering 50% total body surface area. One hour before burn injury, half of the animals underwent gavage with 3 x 10(10) viable C. albicans, a dosage that in previous studies was associated with greater than 90% incidence of yeast translocation to the mesenteric lymph nodes. The other half underwent gavage with an equal volume of saline. After injury, half of each group were randomly selected to receive guinea pig feed ad libitum and the other half were starved for 72 hours. All were allowed access to water ad libitum. Mortality rate was recorded at 3 3 days. The group that underwent gavage with C. albicans and subsequent starvation after burn injury had a significantly higher mortality rate than had any of the other groups. We conclude that induced translocation of C. albicans in guinea pigs increases mortality after burn injury. Moreover, early enteral feeding has a protective effect, presumably by decreasing translocation rates has been shown in previous studies. PMID- 1902479 TI - The decline of power in the Congress and its effect on health care. PMID- 1902478 TI - Antacid, sucralfate, and prostaglandin E2 effects on the growth and potential for translocation of Pseudomonas aeruginosa, Escherichia coli, and Staphylococcus aureus in an in vitro gastric simulation. AB - Viable bacteria in the gut of thermally injured patients may be translocated through the gut mucosa, causing widespread infection. Increased flora from optimization of bacterial growth by pH elevation, coupled with the decreased intestinal motility common among patients whose mucosal integrity has been compromised, may increase the incidence of translocation. Gastric pH in these patients is monitored and maintained around pH 6 by various agents to reduce susceptibility to stress ulceration. Whole milk, given as a nutrient source, also raises pH. An in vitro trial simulating gastric fluid under conditions found in patients with burns was conducted to evaluate the growth of commonly ingested bacteria. Bicarbonate buffer containing pepsin and adjusted to pH 2, 4, or 7 with HCl was dosed with magnesium and aluminum hydroxide antacid (Maalox) (10 ml), sucralfate (Carafate) (0.4 gm), or prostaglandin E2 (PGE2) (10 ng) before inoculation with Escherichia coli (3 x 10(2) organisms), Pseudomonas aeruginosa (3 x 10(2) organisms), or Staphylococcus aureus (2 x 10(1) organisms). Bacterial growth and pH were determined periodically over the 24-hour trial. Milk was added at intervals in half the samples to simulate patient feeding. Maalox increased pH in all samples containing milk (initially pH 2, 4, or 7) to over 7.0 in 2 hours, and increased pH more slowly without milk. Carafate had a moderating effect, increasing pH 2 and pH 4 and decreasing pH 7, with a narrower pH range found in the milk groups. PGE2 treatments combined with milk also increased pH 2 and pH 4, but slightly elevated pH 7 within 24 hours. Without milk, PGE2 did not alter pH from initial values.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1902480 TI - Length of care in patients with severe burns with or without early enteral nutritional support. A retrospective study. AB - The possible influence of early enteral nutritional support on the length of care was explored retrospectively in 25 patients with burns greater than 20% total body surface area (TBSA). Patients were divided into two groups according to the time of their admission: group 1, from July 1986 to February 1987 (n = 12) and group 2, from July 1987 to January 1988 (n = 13). The only difference in treatment between the two groups was the start of early enteral nutritional support in group 2. Age, percent TBSA burned, surfaces of skin grafts, associated respiratory injury, and medical condition were identical in both groups. The following parameters were compared: lag time between hospital admission and the beginning of nutritional support, energy intake, nitrogen intake during the 4 week postadmission period, and length of care. A regression analysis including all patients was also performed to identify the factors associated with length of care. Lag time was shorter in group 2 than in group 1: 3 +/- 2 days versus 7 +/- 2 days (p less than 0.01). Group 2 received more energy than group 1 during the first 2 weeks after admission: 120 +/- 54 kj/kg/day versus 73 +/- 34 kj/kg/day (p less than 0.05) and 175 +/- 36 kj/kg/day versus 137 +/- 41 kj/kg/day (p less than 0.05) for the first and the second week, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1902482 TI - Lupron retards proliferation of ovarian epithelial tumor cells cultured in serum free medium. AB - Some patients with recurrent ovarian epithelial cancer respond favorably to treatment with GnRH agonists. This effect was proposed to be mediated by suppression of pituitary gonadotropin release. The present in vitro study investigated effects of human gonadotropin (Pergonal LH/FSH, 1:1) and Lupron, a GnRH agonist, on proliferation of an ovarian cancer cell line, 2774, which is estrogen receptor negative and grows well in serum-free, defined medium. Pergonal, 10 IU/mL or 30 IU/mL, did not enhance cell proliferation, which argues against stabilization of ovarian tumors in vivo due to decreased serum gonadotropin. Lupron, 1.4 micrograms/mL and 140 micrograms/mL, retarded cell division by day 6-8 of culture, in a dose-dependent manner. Flow cytometric cell cycle phase DNA analysis demonstrated Lupron caused a reversible 5-6% increase in the portion of cells in rest phase, G0/G1, compared to controls during log growth, and a corresponding decrease in the portion of cells in DNA synthesis, S phase. However, long-term culture, 3 weeks, with Lupron failed to arrest cells in G0/G1, and experimental cultures plateaued at cell number similar to control cultures. We conclude Lupron's effect on ovarian cancer cell proliferation is independent of gonadotropin and steroid, involves a cell cycle regulatory event, and duration of benefit observed in vivo for some patients may be related to total tumor volume at the time of treatment. PMID- 1902481 TI - Hydrogen peroxide alters the physical state and function of the plasma membrane of pulmonary artery endothelial cells. AB - Hydrogen peroxide (H2O2) is an important mediator of acute oxidative injury to vascular endothelium. Because the plasma membrane is the initial site of interaction between endothelial cells and extracellular H2O2 produced by stimulated neutrophils or macrophages, we evaluated the effect of H2O2 on the physical state, i.e., fluidity, and function of porcine pulmonary artery endothelial cell plasma membranes. Lactate dehydrogenase (LDH) release, 5 hydroxytryptamine (5-HT) uptake, limiting fluorescence anisotropy (r infinity) for trimethylamino-diphenylhexatriene (TMA-DPH), and conjugated dienes were measured 0.5, 6, and 24 hr after cells were exposed for 30 min to 50-microM H2O2 or Hank's Balanced Salt Solution (control). Compared with control cells, H2O2 caused significant increases in LDH release and in 5-HT uptake 6 hr after exposure. The increase in 5-HT uptake was not blocked by imipramine. H2O2 also caused a significant increase in r infinity for TMA-DPH 0.5 hr after exposure and a significant reduction in r infinity for TMA-DPH 6 hr after exposure. Cellular contents of conjugated dienes were increased 0.5 and 6 hr after exposure to H2O2. Twenty-four hours after exposure LDH release, r infinity, 5-HT uptake, and conjugated dienes had returned to control levels. Preincubation with 50-microM alpha-tocopherol (vitamin E) or 1-mM or 10-mM dimethylthiourea (DMTU) for 1 hr or 24 hr prevented endothelial cell injury, whereas addition of vitamin E or DMTU to the medium 1 hr or 3 hr after H2O2 exposure did not protect against injury. These results indicate that H2O2 causes significant damage to the plasma membrane of pulmonary artery endothelial cells in vitro, leading to alterations in fluidity and leakiness of the membrane. This injury is associated with membrane lipid peroxidation, is reversible, and can be prevented by pretreatment, but not by post-treatment, with vitamin E or DMTU. PMID- 1902483 TI - Sublingual administration of testosterone-hydroxypropyl-beta-cyclodextrin inclusion complex simulates episodic androgen release in hypogonadal men. AB - In search of a more physiological testosterone (T) replacement therapy for hypogonadal states, we evaluated an inclusion complex of T with 2-hydroxypropyl beta-cyclodextrin (HPBCD). HPBCD enhances T solubility and absorption, but HPBCD is not absorbed. Five hypogonadal men (mean age, 32.4 +/- 2.3 yr) with serum T levels below the normal range were treated in two separate experimental phases with either a 2.5- or 5.0-mg tablet of sublingual (SL) T-HPBCD three times daily for 7 days. Acute pharmacodynamic changes were monitored at baseline and 10, 20, and 40 min and 1, 1.5, 2, 3, 4, and 8 h after administration of the first dose. At the 5-mg dose, a maximal concentration (Cmax) of T (85.4 +/- 11.0 nmol/L) was achieved in 20 min (63 +/- 24-fold increase), followed by a rapid decline to below the normal range (less than 12 nmol/L) at 2 h, with an estimated half-life of decline of 1.87 +/- 0.19 h. The dihydrotestosterone (DHT) Cmax (4.1 +/- 0.5 nmol/L) occurred at 32 +/- 5 min (8.9 +/- 1.3-fold increase) and declined to below the normal range (less than 1.2 nmol/L) after 3 h. The integrated 8 h value for the ratio of T/DHT was 10.0 +/- 1.1, which fell within the normal range. The increment in androstenedione paralleled that in T, and the Cmax (6.8 +/- 0.9 nmol/L) was reached in 24 +/- 4 min (2.3 +/- 0.6-fold increase). Compared to baseline, the Cmax was significantly greater for T (P less than 0.005), DHT (P less than 0.0005), and androstenedione (P less than 0.005). Both estradiol (E2) and estrone (E1) remained in the normal range (less than 200 pmol/L), although the Cmax for E1 was significantly greater than baseline (P less than 0.05). Serum LH levels were suppressed (19.0 +/- 2.6%) at 2 h (P less than 0.05), without a significant change in FSH. During 7 days of treatment, there was no cumulative increase in basal T, DHT, and E2 levels or further decline in LH or FSH levels. There was no change in sex hormone-binding globulin levels. Similar results were observed with the 2.5-mg dose, suggesting that the capacity of SL absorption may be limited to a certain dose of T-HPBCD. The fluctuations in T after SL administration of T-HPBCD resemble endogenous episodic secretion. We conclude that T, complexed with HPBCD, is rapidly absorbed by the SL route and quickly metabolized without sustained elevations of DHT or E2. PMID- 1902484 TI - The role of the cholinergic pathway in growth hormone feedback. AB - Cholinergic pathways play an important role in the regulation of GH secretion. To assess their participation in GH feedback, we investigated the effect of pyridostigmine (an acetylcholinesterase inhibitor) on plasma GH responses to GH releasing hormone (GHRH) plus TRH, insulin hypoglycemia, and arginine as well as on the inhibition of these responses by exogenous GH. The GH response to each stimulus was inhibited by an infusion of GH (0.55 micrograms/m2/min), started 4 h earlier. Pyridostigmine (120 mg, orally), administered 30 min before the stimulus, enhanced GH responses to GHRH and insulin during both saline and GH infusions. However, GH responses during combined administration of pyridostigmine and GH were less than those during pyridostigmine alone. GH responses to arginine, in contrast, were not affected by pyridostigmine in either the absence or presence of exogenous GH. TSH responses to TRH were unaltered by either GH or pyridostigmine. Pyridostigmine enhancement of GH responses to a maximally stimulatory dose of GHRH suggests that its effect is exerted by inhibition of somatostatin release. The lack of effect of pyridostigmine on plasma GH responses to arginine suggests that arginine and pyridostigmine increase GH secretion through a common pathway. The enhancement by pyridostigmine of GH responses in both the presence and absence of exogenous GH suggests that exogenous GH and pyridostigmine exert their discordant effects on GH secretion through independent mechanisms. PMID- 1902486 TI - Stimulation of glycosaminoglycan accumulation by interferon gamma in cultured human retroocular fibroblasts. AB - Fully expressed Graves' disease involves an accumulation of glycosaminoglycan (GAG) in the retroocular connective tissue which contributes to the pathogenesis of ophthalmopathy. We treated cultured retroocular and dermal fibroblasts with recombinant interferon gamma (100 U/ml) for 16-24h and measured [3H]GAG accumulation. The cytokine stimulated [3H]GAG accumulation in retroocular fibroblast cultures obtained from eight different donors by 36-124% above control values. In contrast, interferon gamma had no consistent effect on macromolecular accumulation in dermal fibroblast cultures derived from the pretibium or from areas ordinarily uninvolved in Graves' dermopathy. These results suggest that retroocular fibroblasts may be uniquely targeted for one action of interferon gamma which involves the modulation of GAG metabolism. PMID- 1902485 TI - Human follicular fluid contains a follicle-stimulating hormone (FSH) receptor binding inhibitor which has FSH agonist activity, is immunologically similar to FSH, but can be distinguished from FSH. AB - We have previously reported the presence in human follicular fluid (hFF) of a high (greater than 5000) mol wt FSH receptor binding inhibitor (FSH-BI). This hFF FSH-BI was further purified by removal of material insoluble in acidified acetone (pH 4.1) but soluble in diethyl ether (pH 10.5), followed by molecular sieving through Sephacryl S-100. FSH-BI activity eluted from S-100 with an elution volume similar to that of hFSH, but could be distinguished from hFSH on the basis of a differential sensitivity to acid inactivation. Human FSH was inactivated in acetone at pH 4.1 (1 h, 25 C), whereas hFF FSH-BI retained activity under these conditions. Human FF FSH-BI also demonstrated FSH-like agonist activity, defined as the ability to stimulate basal levels of estradiol synthesis in cultured rat Sertoli cells. Human FSH-BI strongly cross-reacted to a commercially available monoclonal antibody used to measure serum hFSH. Indeed, recovery of FSH immunologic activity was significantly greater (134-fold on a mass basis) after partial purification, indicating that antibody recognition sites were apparently masked in unfractionated hFF. In summary, large mol wt hFSH-BI has been partially purified from hFF and found to be similar in size to pituitary hFSH and to have FSH-like agonist activity in vitro. Although distinguishable from pituitary hFSH on the basis of stability to acid, hFSH-BI appears immunologically related to pituitary hFSH so that measurements of hFSH levels in hFF using immunologic techniques should be interpreted with caution. PMID- 1902487 TI - Endocrine response determines the clinical outcome of pulsatile gonadotropin releasing hormone ovulation induction in different ovulatory disorders. AB - To accrue systematic information in different ovulatory disorders on the precise relationship among endocrine response, clinical outcome, and the occurrence of complications, we treated 114 patients with pulsatile GnRH (2.5-5.0 micrograms, iv, every 60 min) for 187 cycles and compared them to 20 normal menstrual cycles. Thirty of these patients had primary hypogonadotropic amenorrhea (PHA; 40 cycles), 33 had other forms of hypogonadotropic hypogonadism (HH; 55 cycles), and 51 had polycystic ovary syndrome (PCOS; 92 cycles). Daily blood samples were drawn for hormone determinations. In PCOS, 50 cycles were preceded by GnRH analog suppression. PHA treatment cycles were characterized by the reestablishment of a normal endocrine pattern, almost no dose-related endocrine differences, elevated ovulatory (93%) and conception rates (23%), and no multiple pregnancies. In the HH subjects the ovulatory (91%) and pregnancy rates (31%) were high; however, while the lower GnRH dose elicited a normal endocrine pattern, the 5-micrograms dose induced excessive folliculogenesis and high estradiol levels and was associated with most of the multiple pregnancies of this study (three of four). GnRH analog suppression was successfully used to avoid recurrence of ovarian over stimulation in two HH subjects. Finally, GnRH analog suppression in PCOS permitted normalization of the follicular phase endocrine pattern, achievement of good ovulatory (76%) and pregnancy (28%) rates, and avoidance of multiple pregnancies; however, luteal phase steroid secretion was abnormal, and the abortion rate remained elevated (43%). Obesity was associated with a reduced ovulatory rate in PCOS, but not in hypogonadotropic, subjects. Thus, we can conclude that in pulsatile GnRH ovulation induction: 1) a profound hypogonadotropic condition, whether spontaneous as in PHA or induced with GnRH analogs as in other ovulatory disorders, is associated with optimal menstrual cycle restoration, high ovulatory and conception rates, and virtually absent risks of multiple pregnancy; 2) residual hypothalamic activity in HH may be responsible for supraphysiological pituitary-ovarian stimulation and result in multiple pregnancy unless a low GnRH dose (2.5 micrograms/bolus) or GnRH analog pretreatment is employed; 3) obesity does not affect treatment outcome in hypogonadotropic patients; and 4) the high spontaneous abortion rate in PCOS may be related to corpus luteum dysfunction. PMID- 1902488 TI - Paradoxical response of growth hormone to peptide histidine methionine in acromegaly: comparison with the effects of thyrotropin-releasing hormone and vasoactive intestinal peptide. AB - We examined whether peptide histidine methionine (PHM) induces a paradoxical rise in plasma GH in patients with acromegaly. PHM (100 micrograms) was given as an iv bolus to eight patients with active acromegaly, and plasma GH levels were measured before and at intervals up to 120 min after the injection. For comparison, the effects of TRH (500 micrograms) and vasoactive intestinal peptide (VIP, 100 micrograms), peptides known to paradoxically stimulate GH secretion in acromegalics, were assessed in all of the patients. A paradoxical rise (greater than 50% above the basal) in plasma GH was observed in five patients after both TRH and VIP administrations, although TRH responders were not always VIP responders, nor did VIP responders always respond to TRH. In two patients, the GH response to PHM fulfilled the criteria of a paradoxical increase. Both of these patients were also TRH and VIP responders. These results suggest that PHM may be another hypothalamic hormone capable of paradoxically stimulating GH secretion in at least some acromegalics, although PHM appears to be a less potent stimulator of GH release than TRH and VIP. The pathophysiological significance of this phenomenon is yet to be determined. PMID- 1902489 TI - Variable tolerance of the developing follicle and corpus luteum to gonadotropin releasing hormone antagonist-induced gonadotropin withdrawal in the human. AB - To examine the differential sensitivity of the ovary to temporary withdrawal of gonadotropin support at different stages of folliculogenesis and corpus luteum function, GnRH antagonist blockade of gonadotropin secretion was examined in 17 studies using the Nal-Glu GnRH antagonist. A vehicle control, antagonist treatment, and follow-up cycle format was used in each study. A previously determined ED100 dose of the Nal-Glu GnRH antagonist (150 micrograms/kg) or vehicle was administered sc every 24 h for 3 consecutive days in the midfollicular phase (MFP), late follicular phase (LFP), and midluteal phase (MLP). In studies in the MFP (n = 7), the largest follicle was 11 +/- 2 mm (mean +/- SEM), and the mean estradiol (E2) level was 220 +/- 44 pmol/L on the first day of antagonist administration. Administration of the antagonist resulted in a 75 +/- 6% suppression of LH (P less than 0.005), no significant change in FSH, and suppression of E2 to the assay detection limit (P less than 0.05). Total cycle length was increased compared to that of the vehicle control cycle (37.3 +/ 1.3 vs. 26.3 +/- 1.1 days; (P less than 0.005) due to prolongation of follicular phase length (P less than 0.005) and reinitiation of folliculogenesis. In the LFP (n = 5), the largest follicle was 16 +/- 1 mm (P less than 0.05 vs. MFP), and the E2 level was 394 +/- 95 pmol/L (P less than 0.05 vs. MFP) on the first day of antagonist administration. Antagonist administration resulted in a 65 +/- 6% suppression of LH (P less than 0.05), a 47 +/- 11% decrease in FSH (P less than 0.05), and no significant change in E2. Total cycle length was prolonged (32.4 +/ 2.2 vs. 25.6 +/- 0.4 days; P less than 0.05) due to an increase in follicular phase length (P less than 0.02); however, the prolongation of the follicular phase was significantly less than that of the MFP (8.0 +/- 1.5 vs. 15.1 +/- 0.1 days; P less than 0.001), suggesting ovulation from the initial dominant follicle. In studies in the MLP (n = 5), LH, E2, and progesterone decreased to the assay detection limit after antagonist administration, while FSH decreased by 36 +/- 4% (P less than 0.05). Menstrual bleeding occurred within 24-48 h of the final Nal-Glu antagonist injection.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1902490 TI - Synthesis of C1 inhibitor in fibroblasts from patients with type I and type II hereditary angioneurotic edema. AB - Patients with hereditary angioneurotic edema (HANE) have serum levels of functionally active inhibitor of the first component of complement (C1 INH) between 5 and 30% of normal, instead of the 50% expected from the single normal allele. Increases in rates of catabolism have been documented in patients with HANE and certainly account for some of decrease in C1 INH level. A possible role for a decrease in synthesis of C1 INH in producing serum levels of C1 INH below the expected 50% of normal has not been well studied. We studied the synthesis of C1 INH in skin fibroblast lines, which produce easily detectable amounts of C1 INH. In type I HANE cells, C1 INH synthesis was 19.6 +/- 4.0% (mean +/- SD) of normal, much less than the 50% predicted. In type II HANE cells, the total amount of C1 INH synthesis (functional and dysfunctional) was 98.9 +/- 17% of normal; the functional protein comprised 43% of the total. Thus, type II HANE cells synthesized functional C1 INH at a much greater rate than for the type I cells. In both type I and II HANE cells, amounts of steady-state C1 INH mRNA levels paralleled rates of C1 INH synthesis, indicating that control of C1 INH synthesis occurred at pretranslational levels. Both type I and type II fibroblasts synthesized normal amounts of C1r and C1s. These data suggest that the lower than expected amounts of functionally active C1 INH in type I HANE may be due, in part, to a decrease in rate of synthesis of the protein, and that the expressions of the normal C1 INH allele in HANE is influenced by the type of abnormal allele present. PMID- 1902491 TI - Respiratory sinus arrhythmia in dogs. Effects of phasic afferents and chemostimulation. AB - We examined the hypothesis that respiratory sinus arrhythmia (RSA) is primarily a central phenomenon and thus that RSA is directly correlated with respiratory controller output. RSA was measured in nine anesthetized dogs, first during spontaneous breathing (SB) and then during constant flow ventilation (CFV), a technique whereby phasic chest wall movements and thoracic pressure swings are eliminated. Measurements of the heart rate and of the moving time averaged (MTA) phrenic neurogram during these two ventilatory modes were made during progressive hypercapnia and progressive hypoxia. RSA divided by the MTA phrenic amplitude (RSAa) showed a power-law relationship with both arterial carbon dioxide partial pressure (PaCO2) and oxygen saturation (SaO2), but with different exponents for different conditions. However, the power-law relation between RSAa and respiratory frequency had an exponent indistinguishable from -2 whether hypoxia or hypercapnia was the stimulus for increased respiratory drive, and during both CFV and spontaneous breathing (-1.9 +/- 0.4, hypoxia, SB; -1.8 +/- 0.7, hypoxia, CFV; -2.1 +/- 0.8, hypercapnia, SB; -1.9 +/- 0.7, hypercapnia, CFV). We conclude that respiratory sinus arrhythmia is centrally mediated and directly related to respiratory drive, and that changes in blood gases and phasic afferent signals affect RSA primarily by influencing respiratory drive. PMID- 1902493 TI - Do-not-resuscitate orders at a chronic care hospital. AB - Do-not-resuscitate (DNR) orders have become an accepted part of medical practice. While these orders have been extensively evaluated in acute care hospitals, little is known about their use in the long-term care setting. We reviewed the medical records of all admissions to a chronic care hospital over a 13-month period, collecting data on selected patient characteristics, use of DNR orders, and patient outcomes during the 6-week period following admission. Fifty-eight of the 301 patients (19.3%) had a DNR order written. Patients' families were involved predominantly in the DNR decision in 73% of the cases while patients themselves were involved in only 18%. Physicians made the decision unilaterally in 6% of the cases. Patients' functional status rather than specific diagnoses predicted the use of DNR orders. Patients with DNR orders were twice as likely to receive new intravenous therapies than patients without those orders (71% vs 33%, P less than 0.01) and four times as likely to die (38% vs 9%, P less than 0.01). They were no more likely to be transferred emergently to an acute care hospital (5% vs 9%, P greater than 0.2). We conclude that DNR orders are not infrequently used, and physicians rarely make the decision unilaterally. Patients with DNR orders have a high likelihood of dying and are infrequently transferred to acute care facilities. PMID- 1902494 TI - Decisionmaking regarding the initiation of tube feedings in the severely demented elderly: a review. PMID- 1902492 TI - Activation of Escherichia coli heat-labile enterotoxins by native and recombinant adenosine diphosphate-ribosylation factors, 20-kD guanine nucleotide-binding proteins. AB - Escherichia coli heat-labile enterotoxins (LT) are responsible in part for "traveler's diarrhea" and related diarrheal illnesses. The family of LTs comprises two serogroups termed LT-I and LT-II; each serogroup includes two or more antigenic variants. The effects of LTs result from ADP ribosylation of Gs alpha, a stimulatory component of adenylyl cyclase; the mechanism of action is identical to that of cholera toxin (CT). The ADP-ribosyltransferase activity of CT is enhanced by 20-kD guanine nucleotide-binding proteins, known as ADP ribosylation factors or ARFs. These proteins directly activate the CTA1 catalytic unit and stimulate its ADP ribosylation of Gs alpha, other proteins, and simple guanidino compounds (e.g., agmatine). Because of the similarities between CT and LTs, we investigated the effects of purified bovine brain ARF and a recombinant form of bovine ARF synthesized in Escherichia coli on LT activity. ARF enhanced the LT-I-, LT-IIa-, and LT-IIb-catalyzed ADP ribosylation of agmatine, as well as the auto-ADP ribosylation of the toxin catalytic unit. Stimulation of ADP ribosylagmatine formation by LTs and CT in the presence of ARF was GTP dependent and enhanced by sodium dodecyl sulfate. With agmatine as substrate, LT-IIa and LT IIb exhibited less than 1% the activity of CT and LT-Ih. CT and LTs catalyzed ADP ribosyl-Gs alpha formation in a reaction dependent on ARF, GTP, and dimyristoyl phosphatidylcholine/cholate. With Gs alpha as substrate, the ADP ribosyltransferase activities of the toxins were similar, although CT and LT-Ih appeared to be slightly more active than LT-IIa and LT-IIb. Thus, LT-IIa and LT IIb appear to differ somewhat from CT and LT-Ih in substrate specificity. Responsiveness to stimulation by ARF, GTP, and phospholipid/detergent as well as the specificity of ADP-ribosyltransferase activity are functions of LTs from serogroups LT-I and LT-II that are shared with CT. PMID- 1902495 TI - Effect of calcium channel blocking agents on the reductive metabolism of halothane. AB - The effect of calcium channel blocking agents on the reductive metabolism of halothane in liver microsomes of guinea pigs was investigated. The reaction mixture for the measurement of the end products consisted of microsomal suspension, 5 mM NADPH, calcium channel blocking agents (verapamil, diltiazem, nicardipine and nifedipine) and halothane in 0.1 M phosphate buffer (pH 7.4). The reductive metabolism of halothane was inhibited competitively by verapamil, diltiazem and nicardipine. The binding spectra for the interaction of these three drugs with cytochrome P-450 in microsomes were investigated. Verapamil caused the reverse type I difference spectrum and diltiazem caused the type I difference spectrum. However, the change caused by nicardipine was not observed by the presence of its specific spectra. NADPH-cytochrome P-450 reductase activity in microsomes did not change by the addition of these three drugs. These results suggest that these three calcium channel blocking agents inhibit the production of radical intermediates during the reductive metabolism of halothane. PMID- 1902497 TI - The role of genetics in autoimmune disease. PMID- 1902496 TI - Evaluation of potential chemoprotectants against microcystin-LR hepatotoxicity in mice. AB - Microcystin-LR (MCLR) is a potent cyclic heptapeptide hepatotoxin produced by the blue-green algae, Microcystis aeruginosa. Toxic blooms of this cyanobacteria have been reported throughout the temperate world. In spite of the potential economic loss and health hazard posed by this toxin, few studies on the development of an antidote have been conducted. Thus, a number of biologically active compounds were tested in mice for effectiveness in preventing the toxicity of a lethal dose of MCLR (100 micrograms kg-1). Efficacy was evaluated based upon the percentage of surviving mice, time to death and serum lactate dehydrogenase activity 45 min after treatment with the toxin. The biologically active compounds were separated into groups based upon proposed mechanisms of action. Enzyme induction by phenobarbital but not by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) resulted in partial protection against toxicity. Calcium channel blockers, free-radical scavengers and water-soluble antioxidants produced little protection against toxicity. The membrane-active antioxidants vitamin E and silymarin, as well as glutathione and the monoethyl ester of glutathione, produced significant protection from lethality. Rifampin and cyclosporin-A, both immunosuppressive and membrane-active agents, which also block the bile acid uptake system of hepatocytes, produced complete protection from the toxicity of MCLR. Thus, lipophilic antioxidants provide partial protection against MCLR toxicity while cyclosporin-A and rifampin are highly effective and potentially useful antidotes. The toxicity of MCLR may depend upon stimulation of the immune system and may be mediated by membrane alterations. PMID- 1902498 TI - [A case of Crigler-Najjar syndrome of type II]. PMID- 1902499 TI - [Stress and peptic ulcers]. PMID- 1902500 TI - Deletions of immunoglobulin C kappa region characterized by the circular excision products in mouse splenocytes. AB - We have identified circular DNAs containing the kappa light chain constant region (C kappa), as well as the excision products of V kappa-J kappa and V lambda-J lambda joining in adult mouse splenocytes. Analysis of C kappa-positive circular DNA clones revealed two recombination sites (intron recombining sequence [IRS]1 and -2) within the germline J kappa-C kappa intron region and the recombining sequence (RS) located downstream of the C kappa exon. While RS contains a conserved heptamer and nonamer separated by a 23-bp spacer on the 5' side, IRS1 sequence is an isolated heptamer without an obvious nonamer, and IRS2 contains a variant heptamer, CACAAAA. Since IRS1 and IRS2 recombined with both RS (23-bp spacer signal) and V kappa (12-bp spacer signal) with significant frequency, intron recombination sites seem to have dual recombination signals. These findings provide direct evidence that C kappa deletion preceding lambda gene rearrangement can occur by looping out and excision. Increased accessibility of inefficient recombinational loci within the intron may enable recombinase to accept wide signal sequence variation. PMID- 1902501 TI - T cell receptor V gene usage of islet beta cell-reactive T cells is not restricted in non-obese diabetic mice. AB - Five islet-reactive T cell clones were established from islet-infiltrating T cells of non-obese diabetic (NOD) mice. All clones expressed CD4, but not CD8, and responded to islet cells from various strains of mice in the context of I ANOD. They could induce insulitis when transferred into disease-resistant I-E+ transgenic NOD mice. The T cell receptor (TCR) sequences utilized by the clones were determined. Their usage of TCR V and J segments was not restricted but was rather diverse. One of the clones utilized V beta 16. The expression of V beta 16 was significantly reduced in I-E+ transgenic NOD, suggesting the possibility that the islet-reactive T cell clone expressing V beta 16 may be deleted or inactivated by I-E molecules. This clone might be one of the candidates that triggers insulitis. PMID- 1902504 TI - High prevalence of Mycoplasma pneumoniae in patients with respiratory tract symptoms: a rapid detection method. PMID- 1902502 TI - In situ studies of the primary immune response to (4-hydroxy-3 nitrophenyl)acetyl. I. The architecture and dynamics of responding cell populations. AB - After primary immunization with an immunogenic conjugate of (4-hydroxy-3 nitrophenyl)acetyl, two anatomically and phenotypically distinct populations of antibody-forming cells arise in the spleen. As early as 2 d after immunization, foci of antigen-binding B cells are observed along the periphery of the periarteriolar lymphoid sheaths. These foci expand, occupying as much as 1% of the splenic volume by day 8 of the response. Later, foci grow smaller and are virtually absent from the spleen by day 14. A second responding population, germinal center B cells, appear on day 8-10 and persist at least until day 16 post-immunization. Individual foci and germinal centers represent discrete pauciclonal populations that apparently undergo somatic evolution in the course of the primary response. We suggest that foci may represent regions of predominantly interclonal competition for antigen among unmutated B cells, while germinal centers are sites of intraclonal clonal competition between mutated sister lymphocytes. PMID- 1902505 TI - Intravenous nitroglycerine in the management of posttreatment hypertension during electroconvulsive therapy. AB - Intravenous nitroglycerine is not described in the psychiatric literature for management of the inevitable and potentially dangerous pressor response encountered in electroconvulsive treatment. However, the anesthesia literature has documented the use of nitroglycerine for the management of similar catecholamine-based hypertension. Unlike other approaches, nitroglycerine creates a controlled, significant, brief vasodilatation after convulsive treatment accompanied by desirable coronary vasodilatation without increased cardiac stress. A review of a series of treatments in which this technique was used confirms the clinical efficacy and safety of this approach. PMID- 1902503 TI - Analysis of the interaction site for the self superantigen Mls-1a on T cell receptor V beta. AB - Superantigen bound to major histocompatibility complex (MHC) products have been shown to stimulate T cells in a V beta-specific manner. Mouse T cells bearing V beta 8.1 usually respond to the self superantigen, Mls-1a, whereas T cells bearing V beta 8.2a do not. Previously, using site-directed mutational analysis, we identified the residues of natural variants of T cell receptor (TCR) V beta 8.2 that conferred Mls-1a reactivity. These residues are predicted to lie on a beta-pleated sheet of the TCR V beta element, well away from the expected binding site for antigen and MHC proteins. This study was undertaken to determine the effect of glycosylation on this beta-pleated sheet on Mls-1a reactivity and to map the extent of the interaction site on V beta 8.2 for Mls-1a. to Mls-1a, as well as to peptides derived from the conventional protein antigen, chicken ovalbumin. Here we demonstrate that first, N-linked carbohydrate on the lateral surface of V beta blocks the interaction of the TCR V beta with the self superantigen, Mls-1a, but has no effect on the TCR interaction with peptide antigen and MHC, second, that the interaction site for Mls-1a extends over the surface of the solvent-exposed beta-pleated sheet on the side of the TCR, and third, that mutations which affect both superantigen and peptide antigen reactivity lie at the beginning of the first complementarity determining region of V beta, consistent with models of the trimolecular complex of TCR-peptide-MHC. PMID- 1902506 TI - Phase II study of ifosfamide with mesna in adult patients with recurrent diffuse astrocytoma. AB - Sixteen patients who developed CT or MRI scan evidence of recurrent diffuse astrocytoma after radiation therapy and nitrosourea-containing chemotherapy received ifosfamide (2500 mg/m2/day for 3 consecutive days) and mesna (500 mg/m2/dose, 5 doses/day for 3 consecutive days). Toxicity consisted primarily of leukopenia in that 60 percent of patients developed leukocyte nadirs less than 1500/mcL. Excessive somnolence occurred in three patients and may have contributed to a case of fatal pneumonia in one patient but was reversible in the other two. No patient had CT or MRI scan evidence of tumor regression. One patient remains stable at 11.3 + months, but all other patients developed evidence of progressive disease less than 6 months from initiation of therapy. The median times to tumor progression and death were 2.0 and 4.8 months, respectively. In conclusion, while ifosfamide and mesna can be given safely at this dose and schedule, there is no evidence of antitumor effect. The degree of leukopenia observed likely would prevent further dose escalation of ifosfamide or addition of other myelosuppressive agents without additional means of bone marrow support in this population of patients. PMID- 1902507 TI - Pharmacokinetics of 11C-labelled BCNU and SarCNU in gliomas studied by PET. AB - This paper describes the study of the pharmacodynamics of two 11C-labelled nitrosoureas, 1,3-bis-(2-chloroethyl) nitrosourea (BNCU) and sarcosinamide chloroethylnitrosourea (SarCNU), both labelled in the carbonyl position. Distribution of the radioactivity as measured by positron emission tomography was compared to the distribution of radioactivity observed after injection of 68Ga EDTA, this being used as an indicator of the blood-brain barrier integrity around the brain tumor. Data suggest that the new nitrosourea, SarCNU, most likely enters brain tissue by different mechanism(s) than BCNU, which enters by diffusion. Data also indicate that use of SarCNU may result in a better tumor to brain ratio than BCNU. PMID- 1902508 TI - Radioimmunodetection of neuroblastoma with iodine-131-3F8: correlation with biopsy, iodine-131-metaiodobenzylguanidine and standard diagnostic modalities. AB - Iodine-131-3F8, a murine IgG3 monoclonal antibody specific for ganglioside GD2 was evaluated by radioimmunoscintigraphy in 42 patients with neuroblastoma. Comparison was made with 131I-metaiodobenzylguanidine (MIBG), 99mTc-methylene diphosphonate (MDP) bone scans, as well as computed axial tomography (CT) or magnetic resonance imaging (MRI). Iodine-131-3F8 detected more abnormal sites (283) than [131I] MIBG (138) or 99mTc-MDP (69), especially in patients with extensive disease. In 20 patients with soft-tissue tumors demonstrated by CT/MRI, 131I-3F8 detected the disease in 18. Upon surgical resection, two tumors interpreted as negative with 131I-3F8 imaging revealed ganglioneuroma, one showing microscopic foci of neuroblastoma. In contrast, 131I-3F8 imaging identified tumors that were confirmed histologically as neuroblastomas. In 26 patients with evidence of marrow disease by antibody scans, 14/26 had confirmation by iliac crest marrow aspirate/biopsy examinations. We conclude that 131I-3F8 scintigraphy has clinical utility in the management of patients with neuroblastoma by improving the sensitivity of tumor detection. PMID- 1902509 TI - The infiltrated radiopharmaceutical injection: risk considerations. PMID- 1902510 TI - Stability of 6-[18F]fluorodopa preparations. PMID- 1902511 TI - Laboratory measurements of nutritional status as correlates of atrophic glossitis. AB - OBJECTIVE: To perform a comprehensive laboratory assessment of nutritional status in two elderly patients selected for the presence of atrophic glossitis, a classic physical sign of malnutrition. DESIGN: Case report. SETTING: Inpatient internal medicine ward at the William S. Middleton Memorial Veterans Medical Center, Madison, Wisconsin. MEASUREMENTS AND MAIN RESULTS: Blood specimens were analyzed by the Nutrition Evaluation Laboratory at the USDA Human Nutrition Research Center on Aging at Tufts University. Both subjects had biochemical evidence of protein-calorie malnutrition and were deficient or marginally deficient in several vitamins and trace minerals. CONCLUSIONS: Much work needs to be done to determine the sensitivity and positive predictive value of the classic physical signs of malnutrition as predictors of low biochemical levels and adverse clinical outcomes. The presence of atrophic glossitis should prompt the clinician to consider a basic nutritional assessment. PMID- 1902512 TI - Limb salvage reconstruction in severe knee infections with associated large soft tissue and bony defects. PMID- 1902513 TI - Automated immunoturbidimetric analysis of six plasma apolipoproteins: correlation with radial immunodiffusion assays. AB - We measured six apolipoproteins (apo AI, AII, B, CII, CIII, and E) by turbidimetric method using an automatic discrete biochemical analyzer and commercially available antisera. The turbidimetric method was compared with the single radial immunodiffusion method. Linearity for serum apolipoprotein assay by the automated turbidimetric method was better than by the single immuno-diffusion method. The linearity by the turbidimetric method was 2.5 G/L for AI, 1.0 G/L for AII, 4.5 G/L for B, 0.12 G/L for CII, 0.3 G/L for CIII, and 0.12 G/L for E. The presence of high concentrations of bilirubin (up to 0.15 G/L) and hemoglobin (up to 50 G/L) interfered with apolipoprotein measurement. Comparison of the immunoturbidimetric and the single radial immunodiffusion (SRID) methods showed excellent coefficients of correlation, r = 0.963, 0.896, 0.846, 0.936, 0.972, and 0.937 for apo AI, AII, B, CII, CIII, and E, respectively. Reference ranges for the six apolipoproteins were determined by using sera from 450 healthy subjects and were 1.4 +/- 0.3 G/L for AI and 0.3 +/- 0.01 for E. The observed levels of AII (P less than 0.001), B (P less than 0.01), and CIII (P less than 0.01) were significantly higher in males. The serum levels of apo B, CII, and E showed a gradual increase with age which was more prominent in females than in males. The levels of apo AI, AII decreased significantly over an 11 day period in 22 patients with myocardial infarction. PMID- 1902514 TI - Immune response to HIV-1 gag antigens induced by recombinant adenovirus vectors in mice and rhesus macaque monkeys. AB - Recombinant adenovirus vectors expressing the entire gag (p55) or CA (p24) region of human immunodeficiency virus type 1 (HIV-1) were constructed by inserting the appropriate HIV DNA sequences into the E3 region of human adenovirus type 5 (Ad5) with and without an exogenous SV40 early promoter. The infectious recombinant adenoviruses Adgag1, AdSVgag1, and AdSVCA1 were shown to express the appropriate HIV-1 antigens in human cells in vitro, as measured by immunoprecipitation and p24 antigen capture assays. Using the p24 antigen capture assay, HIV antigen expressed by AdSVCA1 was detected earlier in infection and in greater amounts than that produced by either Adgag1 or AdSVgag1. In studies concerning the immunogenicity of these vectors, Balb/c (H-2d) mice given a single intraperitoneal injection of 10(7) or 10(8) plaque-forming units of purified vector developed serum antibodies to p24, detected by Western blotting, by 2 weeks postinjection. In the preliminary test of the immunogenicity of the recombinant adenovirus vectors in primates, two of four rhesus macaque monkeys generated antibodies to HIV-1 p24 following two injections of AdSVCA1. As expected, monkeys injected with control adenovirus failed to show any anti-HIV response, and none of the monkeys showed any adverse reactions following infection with either recombinant or control adenoviruses. These results suggest that adenovirus vectors have considerable potential in the study of possible immune therapies for HIV infection. PMID- 1902515 TI - Force decline due to fatigue and intracellular acidification in isolated fibres from mouse skeletal muscle. AB - 1. Single, intact muscle fibres from the flexor brevis foot muscle of the mouse have been fatigued at 25 degrees C by 350 ms, 70 Hz stimulation trains, initially delivered every 3.8 s and then at stepwise decreasing intervals until tension was down to about 30% of the original (Po). Rested fibres generated a specific force of 372 +/- 8.4 kPa (mean +/- S.E.M., n = 25). 2. Endurance, defined as time to attain 0.5 Po, varied from 2.5 to 24 min, with the majority of fibres falling in the range 4-8 min, corresponding to 70-160 tetani. In all fibres where it was followed, tension recovery after cessation of stimulation was 90% or better. 3. Tetanic force declined in a characteristic way during fatiguing stimulation: initially tension fell to about 0.85 Po during eight to fourteen tetani (phase 1), then followed a long period of nearly steady tension generation (phase 2) and finally there was a rapid force decline (phase 3). 4. Caffeine (15 or 25 mM) caused a slight potentiation of tetanic force in the rested state (4.7 +/- 0.9%, n = 21) and slowed relaxation. No change in resting tension was seen with caffeine at concentrations up to 25 mM. 5. Caffeine (15-25 mM) caused a rapid and dramatic increase in tetanic force when applied to severely fatigued fibres: force output rose from 29.8 +/- 1.5 to 82.5 +/- 1.2% (n = 13) of Po. During phase 2 force potentiation with caffeine was much smaller. 6. A 10 s pause resulted in a large, transient force increase when imposed during phase 3 but had little effect on force production during phase 2. 7. Intracellular acidosis, induced by superfusion with Tyrode solution gassed with 30% CO2 instead of the normal 5% (extracellular pH 6.5 vs. 7.3), resulted in a fall in tetanic tension to about 0.85 Po (n = 7). This depression could to some extent be counteracted by 15 mM caffeine, which brought tension back to about 0.90 Po. 8. It is concluded that there are at least two mechanisms for force decline during fatiguing stimulation: one which manifests itself early and is likely to be related to cross-bridge function and another representing deficient Ca2+ handling which becomes prominent at a later stage. For severe fatigue (0.3 Po) the latter mechanism is dominant. PMID- 1902516 TI - Slowing of relaxation during fatigue in single mouse muscle fibres. AB - 1. In the preceding paper we analysed the force decline in fatigue of isolated mouse muscle fibres. Using the same preparation and stimulation scheme we have now examined another aspect of muscle fatigue, namely slowing of relaxation. 2. Relaxation at the end of a tetanic contraction can usually be divided into two phases, an initial nearly linear force decline, followed by an exponential phase. We have analysed the initial phase in terms of decline rate and duration. In rested fibres the decline rate after a 350 ms tetanus was not affected by a 30% reduction of tetanic tension (obtained by decreasing the stimulation frequency). 3. Relaxation became gradually slower during fatiguing stimulation with a maximum reduction at the time when tetanic tension was reduced to about 75% of the original (end of phase 2, see preceding paper). At this time the decline rate of the linear phase had fallen to 55.2 +/- 2.9% (mean +/- S.E.M., n = 25) and its duration had increased to 151.3 +/- 14.2% of the control (unfatigued 350 ms, 70 Hz tetanus). 4. Short rest periods (duration = 10s), given at various times during fatiguing stimulation, resulted in a clear, but partial, normalization of the relaxation parameters; at the time of maximum slowing the mean decline rate increased from 50.3 to 58.7% and the duration decreased from 167.9 to 144.0% of the control (n = 14). 5. The influence of intracellular acidosis on relaxation was studied by exposing rested fibres to 30% CO2 instead of the normal 5%. This resulted in a decline rate of 43.0 +/- 2.6% and a duration of 221.1 +/- 13.1% of the control (n = 7). 6. In amphibian muscle relaxation is known to become gradually slower during a single, prolonged tetanus. The existence of such an effect also in the present preparation was studied by giving 'interrupted' tetani with a total duration of about 2 s. In rested fibres the mean rate of relaxation was found to fall from 140.9 to 71.8% (n = 11) of the control (end of 350 ms stimulation) with a time constant of about 0.5 s. Thus, a marked slowing during a long tetanus occurs also in mammalian muscle. 7. A distinct slowing of relaxation during prolonged tetani was observed also in the fatigued and in the acidified state. Under these two conditions the mean rate of relaxation fell from 87.0 to 34.0% (n = 3) and from 74.0 to 23.0% (n = 5) of the control, respectively, with time constants similar to that in the rested state.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1902518 TI - Hemarthrosis in patients with acquired factor VIII inhibitor. AB - We describe 2 patients who presented with hemarthrosis and were found to have an underlying Factor VIII inhibitor. One case was associated with a renal cell carcinoma. Factor VIII inhibitor should be included in the differential diagnostic lists of causes of hemarthrosis. PMID- 1902517 TI - Substrates for muscle glycogen synthesis in recovery from intense exercise in man. AB - 1. Intramuscular glyconeogenesis from lactate after intense exercise was examined by using the one-legged knee extension model which enables evaluation of metabolism in a well-defined muscle group. 2. In seven subjects measurements of leg blood flow and arterial-venous differences of various substrates were performed in individuals after intense, exhaustive knee extensor exercise lasting 3.0 min. Muscle glycogen and lactate concentrations were determined in the quadriceps muscle immediately after exercise and three times during 1 h of recovery. 3. Muscle glycogen increased from 93.7 +/- 6.7 (+/- S.E.M.) to 108.8 +/ 8.1 mmol (kg wet wt)-1 during the recovery period. Muscle lactate was 27.1 +/- 2.1 mmol (kg wet wt)-1 at the end of exercise and decreased to 14.5 +/- 2.1, 6.7 +/- 1.1, and 3.0 +/- 0.5 mmol (kg wet wt)-1 after 3, 10 and 60 min of recovery, respectively. 4. More than two-thirds of the lactate that accumulated in the muscle during the intense exercise was released into the blood. It was estimated that between 13 and 27% of the lactate could have been converted to glycogen. This corresponded to a glycogen resynthesis rate from lactate of 0.17-0.34 and 0.002 mmol glucosyl units min-1 (kg wet wt)-1 for the first 10 and last 50 min of recovery, respectively. 5. The O2 debt of the leg was 1.5 l of which the resynthesis of ATP, creatine phosphate (CP) and glycogen and reloading of haemoglobin (Hb) and myoglobin (Mb) only could account for one-third. It is proposed that the elevated oxygen uptake during recovery is linked to the metabolic use of intramuscular triacylglycerol. PMID- 1902519 TI - Postoperative primary adrenal failure in a patient with anticardiolipin antibodies. AB - A 50-year-old woman with no history of thrombosis or recurrent abortions developed pulmonary thromboembolism and bilateral hemorrhagic adrenal infarction with adrenal failure after hysterectomy for uterine fibroids. Anticardiolipin antibodies (aCL) were detected in high titer and have persisted. She remains well, without further thromboses, taking steroid replacement and warfarin anticoagulation. The initial presentation of aCL related disease can be as thrombotic postoperative complications in middle-age. PMID- 1902520 TI - Mutation spectrum following transfection of ultraviolet-irradiated single stranded or double-stranded shuttle vector DNA into monkey cells. AB - We designed a shuttle vector system that allowed a comparison of the mutation spectrum on the supF target gene after transfection of single-stranded or double stranded DNA into monkey cells. Single-strand-derived plasmids exhibited a spontaneous mutation frequency tenfold higher than double-strand-derived ones. These spontaneous mutations comprised deletions and point substitutions. This system was applied to the study of ultraviolet-induced mutagenesis. Single stranded DNA exhibited a lower survival and a higher mutation frequency than double-stranded DNA after identical ultraviolet-irradiation. The use of single stranded DNA allowed us to confirm and complete the data about the targeting of ultraviolet-induced mutations and the exact nature of the base changes involved. One class of mutations was more frequent after transfection of ultraviolet irradiated single-stranded DNA than for double-stranded DNA: frameshifts represented 10% of the mutants. Multiple mutations, attributed by some authors to an error-prone excision repair process, have also been observed in the spontaneous and ultraviolet-induced mutation spectra following single-stranded DNA transfection, although it cannot be a direct substrate for excision repair. PMID- 1902521 TI - Purification, crystallization and preliminary crystallographic analysis of porcine aldose reductase. AB - Large crystals of porcine aldose reductase have been grown from polyethylene glycol solutions. The crystals are triclinic, space-group P1, with a = 81.3 A, b = 85.9 A, c = 56.6 A, alpha = 102.3 degrees, beta = 103.3 degrees and gamma = 79.0 degrees. The crystals grow within ten days to dimensions of 0.6 mm x 0.4 mm x 0.2 mm and diffract to at least 2.5 A. There are four molecules in the unit cell related by a set of three mutually perpendicular non-crystallographic 2-fold axes. PMID- 1902523 TI - Sero-diagnosis of schistosomiasis by ELISA test in an endemic area of Gimvi village, India. AB - Enzyme-linked immunosorbent assay (ELISA) was carried out in Gimvi village, India, using antigens derived from S. haematobium and S. mansoni adult worms. Patients excreting schistosome ova in urine elicited positive ELISA titres, whereas patients who were previously positive but are no longer passing viable eggs were negative for ELISA. PMID- 1902522 TI - Controlling basal expression in an inducible T7 expression system by blocking the target T7 promoter with lac repressor. AB - Effects of placing a lac operator at different positions relative to a promoter for bacteriophage T7 RNA polymerase were tested. Transcription can be strongly repressed by lac repressor bound to an operator centered 15 base-pairs downstream from the RNA start, but T7 RNA polymerase initiates transcription very actively from this T7lac promoter-operator combination in the absence of repressor, or in the presence of repressor plus inducer. Sequence changes in the transcribed region were found to make transcription from some T7 promoters, including the T7lac promoter, more sensitive to inhibition by T7 lysozyme. The pET-10 and pET 11 series of plasmid vectors have been constructed to allow target genes to be placed under control of the T7lac promoter and to be expressed in BL21(DE3) or HMS174(DE3), which carry an inducible gene for T7 RNA polymerase. These vectors carry a lacI gene that provides enough lac repressor to repress both the T7lac promoter in the multicopy vectors and the chromosomal gene for T7 RNA polymerase, which is controlled by the lacUV5 promoter. Very low basal expression of target genes is achieved, but the usual high levels of expression are obtained upon induction. Addition of T7 lysozyme can reduce basal expression even further and still allow high levels of expression upon induction. Genes that are very toxic to Escherichia coli can be maintained and expressed in this system. PMID- 1902524 TI - Sporocysts isolated from the southern copperhead (Agkistrodon contortrix contortrix) produce Sarcocystis montanaensis-like sarcocysts in prairie voles (Microtus ochrogaster). AB - Sporulated oocysts and free sporocysts of a Sarcocystis sp. were isolated from the feces of a southern copperhead (Agkistrodon contortrix contortrix) collected in Arkansas (USA). Twenty sporocysts measured 11.2 by 8.5 microns, lacked a Stieda body, and had four sporozoites and a granular sporocyst residuum. Sarcocysts similar to those of Sarcocystis montanaensis were present in the tongues of prairie voles (Microtus ochrogaster) inoculated orally with 800 sporocysts 128 days previously. Sarcocysts were thin-walled, divided into compartments by septa, and had electron dense projections (0.14 microns) on the primary cyst wall. Infection was not pathogenic for prairie voles under the conditions of this study. No infections were observed in ICR strain laboratory mice (Mus musculus) or white-footed mice (Peromyscus leucopus) following oral inoculation of 800 sporocysts. PMID- 1902525 TI - Mortality in Atlantic salmon (Salmo salar) associated with trichodinid ciliates. AB - A protozoan infection (Trichodina truttae) was identified in captive Atlantic salmon (Salmo salar) kelts that died in spring of 1988 and 1989. Fish with intense infections showed signs of listlessness, erratic swimming and inappetence. The infection induced excessive mucus secretion, epithelial sloughing and lesions that probably permitted entry of opportunistic bacteria which eventually caused ulcers and death. A seawater bath for 30 min each week for 4 wk effectively controlled the parasite. PMID- 1902526 TI - The role of H2-receptors in chronic. pharyngitis? PMID- 1902527 TI - Chloramphenicol therapy of typhoid fever. AB - In a prospective study we compared two different dosage regimens of IV chloramphenicol succinate (100 mg/kg/day and 75 mg/kg/day) in children with culture proven typhoid. Trough and peak blood samples, obtained at 48 hrs, were analysed for free chloramphenicol by high pressure liquid chromatography (HPLC). Although the mean trough (8.8 +/- 7.7 versus 5.4 +/- 2.6 mcg/ml) and peak (19.9 +/- 12.2 versus 15.4 +/- 6.1 mcg/ml) chloramphenicol concentrations were comparable in both groups, a significantly wider range was found in the group receiving 100 mg/kg/day. Potentially toxic levels (greater than 30 mcg/ml) developed in two patients with liver dysfunction. Chloramphenicol in a dosage of 75 mg/kg/day is adequate and safe for the treatment of paediatric typhoid. PMID- 1902528 TI - Gestational diabetes in a developing country, experience of screening at the Aga Khan University Medical Centre, Karachi. AB - In order to determine the prevalence of glucose intolerance in pregnancy, 1267 consecutive women attending the antenatal clinic of the Aga Khan University Medical Centre were subjected to a 75 g glucose challenge followed 2 hr later by plasma glucose determination irrespective of gestation on the first antenatal visit. The test was repeated at 28-32 weeks of gestation if the patients had an abnormal initial screen at less than 28 weeks gestation and a normal glucose tolerance test on diagnostic follow-up and for those who had a risk factor for gestational diabetes and a normal initial screen at less than 28 weeks gestation. The glucose challenge test was abnormal (2 hr plasma glucose greater than 140 mg%) in 8.6% of the screened population. Follow-up oral glucose tolerance test on these patients revealed a prevalence of 3.2% of gestational diabetes and 1.9% of impaired glucose tolerance test based on the modified O'Sullivan criteria. Improvement in cost effectiveness of screening programmes was adjudged possible by avoiding glucose tolerance tests in patients with 2 hr plasma glucose value of greater than 170 mg% after a 75 g oral glucose challenge for screening. PMID- 1902529 TI - Bacteriological and protozoal study on domestic water supply in Karachi. AB - Four hundred and fifty eight water samples collected from domestic tanks and taps and community taps were analysed for bacterial contamination. Faecal pollution was more in domestic tanks and taps in Mehmoodabad, Korangi and least in water collected from community taps of Liaquatabad, Korangi and Mehmoodabad. Bacteria isolated were mostly E. coli, Enterobacter sp, Klebsiella sp. and A. faecalis, while other organisms (except Pseudomonas) were found in lower numbers. Salmonella para typhi and para typhi B, Shigella dysenteriae and Aeremonas sp. were found in Clifton area. Parasite (Fluke) was isolated from one water sample only. PMID- 1902530 TI - Bacterial isolates in neutropenic febrile patients. AB - One hundred consecutive patients with documented bacteremia and neutrophil count of 0.5 x 10(9)/L or below were retrospectively studied to determine the pattern of infection at the Aga Khan University Hospital in Karachi. These included patients with primary haematologic malignancies presenting with low counts, and those patients with cancer who developed neutropenia as a result of chemotherapy. The gram negative organism pseudomonas aeruginosa was the most common bacterial organism isolated constituting 31% of all positive blood cultures. Gram positive organisms were frequently isolated comprising 24% of all isolates of which 15% were Staph.aureus. Staph. epidermidis was not isolated in this series. Salmonella species were isolated in 9 patients. The other gram negative rods included non lactose fermenting organisms frequently isolated in a nosocomial setting including Serratia and Acinetobacter. Four patients had positive fungal blood cultures. A single positive anaerobic culture was obtained. Sensitivities of the Pseudomonas aeruginosa reflected the high frequency of resistance seen in nosocomial isolates and those from the community. More than half (54.8%) of the isolates were resistant to carbenicillin and 9.6% resistant to gentamicin. Although 3.2% were resistant to cefotaxime, none were resistant to ofloxacin or ceftazidime reflecting the relatively recent arrival of the latter. In contrast, 23% of Staph. aureus were still sensitive to penicillin. Methicillin (cloxacillin) resistant Staph. aureus did not occur. However 26.6% of the Staph. aureus were resistant to erythromycin. Knowledge of the prevailing pattern of infection permits the development of investigative and therapeutic approaches of optimal efficacy. PMID- 1902531 TI - Clinical features and management of malignant ascites. AB - Retrospective analysis of 45 patients (33 females, 12 males) with cytologically proven malignant ascites is presented. Abdominal pain was the most frequent symptom (69%). Fiftythree percent cases had low serum albumin. Ascitic fluid was haemorrhagic or serosanguinous in 48% cases, in the rest it was clear or straw coloured. Peritoneal effusion was exudative in 84% cases. Mean glucose content of ascitic fluid was 95 mg/dl and the mean white cell count of 919 cells/cmm. Vast majority (82%) of the cases had metastatic adenocarcinomas. Primary malignancy was mostly ovarian (47%) followed by non-Hodgkin's lymphoma (11%) and gall bladder carcinoma (9%). Primary site could not be identified in 13% cases. Sixty two percent patients received systemic chemotherapy for the underlying malignancy, of these 43% had complete or partial resolution of the ascites. Of the patients whose long-term follow-up is available, 54% were alive with a median follow-up of 9 months. PMID- 1902532 TI - Alexithymia in Karachi. AB - Alexithymia is a new term which usually means "no words for mood" and used to describe a disorder where patients have difficulty in expressing feelings in words. Such patients therefore express emotions in somatic terms. We have selected headache as a symptom to test the term Alexithymia. A group of thirty patients with the complaint of persistent headache of more than 6 months duration, without any organic pathology or neurological disease entity was taken. This study concludes that Alexithymic traits are not necessarily more prominent in those having psychophysiological symptoms specially tension headache. It also shows that we should not accept any new concept evolved in West without testing it in our own conditions. PMID- 1902533 TI - Carriage of group B streptococci in rectum and urogenital tract of pregnant women. AB - One hundred pregnant women in third trimester were screened for the carriage of group B streptococci (GBS) in a prospective study. Rectal and urogenital samples were collected, 25% women were positive for non group B beta haemolytic streptococci. Twelve (48%) were positive at single site and 13 (52%) at more than one site. Beta haemolytic streptococci isolated were non-groupables in 19 (76%) and groupables in 6 (24%). Among groupables, Group D streptococci (GDS) were the commonest 3 (12%) followed by Group G2 (8%) and Group F1 (4%). Group B streptococci were not isolated in our study population. PMID- 1902534 TI - Clinical microbiology. PMID- 1902535 TI - [A method of detecting tubercle bacilli in sputum]. AB - Tubercle bacilli were injected intravenously to mice after dusts were injected into their subcutaneous tissue. Out of 23 kinds of dusts tested, a quartz dust enhanced most the growth of mycobacteria injected intravenously in mice. Based on this a mixture of the sputum from patients with pulmonary tuberculosis and finely powdered crystalline silica was inoculated subcutaneously into the flanks of mice. Growth of tubercle bacilli was demonstrated occasionally for the sputum specimens from smear-positive and culture-negative cases, and even for smear- and culture negative cases. When a sputum specimen which yielded many colonies on routine egg medium were tested, the growth of bacteria became visible as early as 2 weeks after inoculation. On the other hand, it took 3 to 4 weeks for the visible growth of bacilli, when a sputum specimen yielded only a few or no colonies on culture medium. In this method, the bacilli appeared earlier and more frequently than in the routine culture method on egg medium. Thus an inoculation into mice with a mixture of the sputum and quartz powder was shown to be a sensitive method for the diagnosis of pulmonary tuberculosis. PMID- 1902536 TI - [Myocardial infarction]. AB - The author presents his original experience in diagnosis and treatment of myocardial infarction. It should be managed at three stages: prehospital, hospital (in a special infarction unit) and rehabilitation (in a country center). Much importance is given to prehospital diagnosis which should be early, to anesthesia and differential treatment policy in hospital. Various treatment regimens are reviewed, so are the results of short- and long-term effects of thrombolytic therapy. PMID- 1902537 TI - Ewing's sarcoma in children: twenty-five years of experience at the Instituto Portuges de Oncologia de Francisco Gentil (I.P.O.F.G.). AB - Fifty children with Ewing's sarcoma were consecutively treated from 1962 to 1987 and retrospectively analyzed at the I.P.O.F.G. of Lisbon. At first diagnosis, 10 cases had distant metastases. The remaining 40 patients had clinically localized disease, and different protocols were followed over the years. The best results were obtained with chemotherapy and radiotherapy with or without surgery; and for these children the two-year survival rate was 42.8% vs. 8.3% for the group of patients submitted to local treatment alone. Besides the treatment modality, other factors influenced the prognosis, such as inflammatory signs, sex, tumor volume, and tumor site as well as evidence of distant metastases. PMID- 1902538 TI - Influence of initial reperfusion pressure after hypothermic cardioplegic ischemia on endothelial modulation of coronary tone in neonatal lambs. Impaired coronary vasodilator response to acetylcholine. AB - To examine the effect of initial coronary reperfusion pressure on endothelial function, we subjected 16 isolated perfused neonatal lamb hearts to 2 hours of ischemia with potassium cardioplegic solution followed by reperfusion for 1 hour. Before ischemia both acetylcholine, an endothelium-dependent vasodilator, and nitroglycerin, and endothelium-independent vasodilator, caused coronary vasodilation. After ischemia the response to acetylcholine was impaired in the eight hearts with high initial reperfusion pressure (60 mm Hg) but was intact in the eight hearts with low initial reperfusion pressure (20 mm Hg for 10 minutes, 40 mm Hg for 10 minutes, and then 60 mm Hg thereafter). The response to nitroglycerin, however, remained intact regardless of initial reperfusion pressure. Recovery of resting coronary flow and myocardial oxygen consumption was lower in the group with high pressure reperfusion than in the group with low pressure reperfusion. On reperfusion a transient burst of coronary flow was exhibited by the hearts reperfused at high pressure. These results suggest that high initial reperfusion pressure impairs the endothelial modulation of coronary tone; this may be related to the effects on the coronary vasculature of the "burst" of coronary flow associated with high intravascular pressure. PMID- 1902539 TI - Intermediate term results of infant orthotopic cardiac transplantation from two centers. AB - Orthotopic cardiac transplantation has become established for selected infants with severe forms of congenital heart disease. This study reviews the combined experience and intermediate term results of infants undergoing orthotopic cardiac transplantation from Children's Memorial Hospital, Chicago, and Kosair Children's Hospital, Louisville. From June 1986 through December 1989, 20 orthotopic cardiac transplantations were performed in 19 patients. Sixteen patients had variants of hypoplastic left heart syndrome. One infant had anomalous origin of the left coronary artery with severe ischemic cardiomyopathy. Two infants had aortic stenosis with endocardial fibroelastosis, and one had extracorporeal membrane oxygenation as a bridge to transplantation. Immunosuppression included cyclosporine, azathioprine (Imuran), and corticosteroids with an effort to wean the patients from steroids by 6 months to 2 years. Three early deaths resulted- from technical errors in two patients and from hyperacute rejection in one patient at 3 days. Four late deaths have occurred. Two patients died at 2 and 13 months of acute rejection. One patient died at 15 months of acute rejection after retransplantation. One patient died at 7 months of respiratory syncytial viral pneumonia. The remaining 12 patients are surviving 5 to 47 months (means 20 months) after orthotopic cardiac transplantation. Rejection surveillance in the first 6 months is by clinical signs supplemented by echocardiography, electrocardiography, and cell cycle analysis; endomyocardial biopsy is used after 6 months of age. For the cumulative series, 24 episodes of suspected rejection have been treated during 277 at-risk patient months with intravenous methylprednisolone (Solu-Medrol) (n = 18) and monoclonal antibody (OKT3) (n = 6), for an incidence of 1.04 episodes of rejection per patient per year. Serious posttransplantation infections including endocarditis, catheter sepsis, meningitis, and colonic perforation were successfully treated in four patients. Subjectively, their quality of life is excellent as shown by normal growth and developmental milestones and a low hospital readmission rate (1.4 episodes per patient per year). These encouraging intermediate term results warrant continued application of infant orthotopic cardiac transplantation for severe forms of congenital heart disease. PMID- 1902540 TI - [Cost-effectiveness analysis of home administration versus hospital administration of intravenous immunoglobulin]. AB - A prospective analysis was carried out to evaluate the cost-effectiveness of two alternatives for the treatment of hypo-agammaglobulinemia with intravenous immunoglobulin: the current hospital administration and the administration in the patient's home. 38 patients or relatives were surveyed about their personal or family characteristics, current therapy and the possibility to be treated at home. Home therapy is feasible--43% of the patients would be able to have it and would prefer it--and less costly, as costs could be reduced in 18-20%. This alternative is felt as a greater patient's independence, with less feeling of illness and preventing the loss of school or work hours. 32% prefer the hospital because they feel more secure in it. PMID- 1902541 TI - [Loss of intravenous nitroglycerin administered with polyvinyl chloride infusion systems]. AB - To evaluate the consequences of the interaction between intravenous nitroglycerin (NTG) and infusion systems made of polyvinyl chloride (PVC), 20 dilutions of NTG were prepared in glass bottles with an initial concentration of 200 micrograms/ml, which were infused through 20 infusion systems at a rate of 20 ml/hour during 12 hours. NTG concentrations collected at the terminal part of the infusion systems were evaluated after 5 minutes, 6 hours and 12 hours. The results showed a substantial loss of NTG through PVC systems. The loss was 20% after 5 minutes and up to 32% after 12 hours. These results, obtained with a preparation similar to that used in clinical practice, may be helpful to estimate the real dose of the infused drug. PMID- 1902542 TI - [Ovarian cancer in a female patient with von Recklinghausen's disease]. AB - A 29-year-old female with von Recklinghausen's disease developed ovarian epithelial cancer. Neurofibromatosis is a dominant autosomal disease predisposing to a wide range of tumors. The association between neurofibromatosis and malignancy was reviewed, analyzing the relevant features for the present case. PMID- 1902544 TI - Renal hemodynamics in experimentally galactosemic dogs and diabetic dogs. AB - To examine the association between renal hemodynamic abnormalities and the development of diabetic kidney disease, glomerular filtration rate (GFR) and renal plasma flow (RPF) have been determined in dogs with alloxan-induced diabetes or experimental galactosemia of 1 to 5 years duration. GFR and RPF were significantly greater than normal in insulin-deficient diabetic dogs. GFR was also significantly greater than normal in the galactosemic animals, and RPF tended to be elevated even though GFR and RPF were measured at time of day when plasma galactose is no longer elevated. GFR and effective RPF (eRPF) were found to increase in normal animals upon acute elevation of blood galactose or glucose concentration. Thus, GFR is supranormal in experimental galactosemia, as well as in diabetes, although galactosemia has been shown not to cause nephromegaly, mesangial expansion, or glomerular obliteration, which are typical of diabetes. Administration of an aldose reductase inhibitor (Sorbinil) at dosages sufficient to significantly reduce erythrocyte polyol concentration did not significantly influence GFR or RPF in diabetic or galactosemic dogs. PMID- 1902543 TI - The effect of transient dopamine antagonism on thyrotropin-releasing hormone induced prolactin release in female rats during the estrous cycle. AB - Prolactin (PRL) release induced by TRH was examined on each day of the estrous cycle in female rats in which pituitary dopamine (DA) receptors were blocked pharmacologically. The objective was to determine if an interaction exists between hypothalamic inhibitory and releasing hormones with regard to prolactin (PRL) secretion. Domperidone (0.01 mg/rat i.v.) followed 5 minutes later by the administration of the DA agonist 2-Br-alpha-ergocryptine maleate (CB-154, 0.5 mg/rat i.v.) were used to produce a transient (less than 1 hr) dopamine blockade. One hour later, thyrotropin-releasing hormone (TRH, 1.0 microgram/rat i.v.) was given to stimulate PRL release. On the morning of proestrus, TRH released a significantly greater quantity of PRL into the plasma after DA antagonism compared to control animals which did not receive the dopamine antagonist. Dopamine antagonism also enhanced the effectiveness of TRH on the mornings of estrus and metestrus. The response on estrus was significantly greater than the response on proestrus. However by the morning of diestrus, TRH-"releasable" PRL was greatly diminished. Our results suggest that DA antagonism is able to shift differing quantities of PRL into a TRH "releasable" pool on several days of the estrous cycle and that the control of this mechanism is acute. PMID- 1902545 TI - Inability to detect an inhibitor of thyroxine-serum protein binding in sera from patients with nonthyroid illness. AB - Sera from 111 patients hospitalized on acute-care wards (including 32 in the intensive care unit) were examined for the possible presence of inhibitors of thyroxine (T4)-serum protein binding in an assay employing equilibrium dialysis. In 38 of these sera, the unbound (free) T4 fraction was 50% or more higher than the free T4 fraction in a pool of normal sera. From the free T4 fraction in each of the 111 serum samples and the free T4 fraction in the pool of normal sera, the predicted free T4 fractions in mixtures (1:1) of each of these sera with the normal pool were calculated (assuming the absence of binding inhibitors) from the appropriate mass action equations. It was reasoned that a free T4 fraction in any mixture that exceeded this predicted value would indicate the possible presence of a binding inhibitor. (The normal pool was selected for having a low serum triglyceride concentration, to minimize in vitro generation of free fatty acids.) However, for the 111 serum samples studied, the free T4 fraction in the mixture exceeded the upper 95% confidence limit of this predicted value in only one case, and then just barely. Thus, evidence for an inhibitor of T4-serum protein binding in sera from patients with nonthyroid illness could not be found. Twenty-eight of the serum samples were also examined in a similar assay that employed ultrafiltration of undiluted serum instead of equilibrium dialysis. Evidence for an inhibitor of T4-serum protein binding similarly could not be found. Because part of the reason for postulating the existence of such a binding inhibitor has been the performance of the triiodothyronine (T3) resin uptake test in patients with nonthyroid illness, an alternative explanation for this phenomenon was sought. When thyroid hormone-binding globulin (TBG) was desialylated by treatment with neuraminidase, its avidity for T4 was markedly decreased, but its avidity for T3 was unchanged. Thus, if desialylated TBG circulates in patients with nonthyroid illness as previously reported, it could explain not only the low serum T4 concentrations despite near normal immunoreactive TBG concentrations, but also the poor performance of the T3 resin uptake test (where T4 binding capacity is overestimated) in these patients. PMID- 1902546 TI - Effects of pravastatin, a new HMG-CoA reductase inhibitor, on vitamin D synthesis in man. AB - The HMG-CoA reductase inhibitors, a new class of lipid-lowering agents being used with increasing frequency, inhibit synthesis of cholesterol in vivo. Thus, one potential side effect of these drugs is alteration of other metabolic pathways requiring intermediates in the cholesterol biosynthetic pathway. We hypothesized that pravastatin, a new HMG-CoA reductase inhibitor, may impair vitamin D3 synthesis in the skin and alter mineral homeostasis by diminishing the availability of vitamin D precursors. Basal serum levels of calcium, phosphorus, parathyroid hormone (PTH), vitamin D3, and 1,25-dihydroxyvitamin D were measured, and dietary intakes of calcium and vitamin D were calculated in a control hypercholesterolemic group and an experimental group treated with pravastatin 10, 20, and/or 40 mg orally twice daily for at least 3 months. Basal parameters of mineral metabolism were similar in the two groups. To assess the capacity of the skin to synthesize vitamin D3 and as an indirect measure of its precursors, all subjects received whole body ultraviolet irradiation (UVI) in a phototherapy chamber for varying time intervals. Subjects in both groups showed significant (P less than .001) dose-dependent increases in vitamin D3 production after equivalent UVI exposures. However, for equivalent UVI exposure, the serum vitamin D3 response was identical in controls versus pravastatin-treated subjects. We conclude that hypercholesterolemic patients have normal mineral metabolism and the use of pravastatin at these doses for up to 3 months does not alter vitamin D3 synthesis in the skin. PMID- 1902547 TI - Reversible neurotoxicity following hyperfractionated radiation therapy of brain stem glioma. AB - Two patients with brain stem gliomas were treated with hyperfractionated radiation therapy (HFR) (7,020 and 7,560 cGy, respectively). Despite initial clinical improvement during irradiation, both patients demonstrated clinical deterioration approximately 3 weeks after completion of radiotherapy. Cranial magnetic resonance imaging (MRI) revealed a progressive increase in distribution of abnormal brain stem signal consistent with either tumor or edema. 18FDG positron emission tomography (PET) was obtained in one patient and demonstrated a hypermetabolic lesion at diagnosis and a hypometabolic lesion at the time of clinical deterioration postirradiation. Management with a tapering dose of dexamethasone alone resulted in marked clinical (both patients) and radiographic (one patient) improvement, allowing reduction or discontinuation of this medication. These results suggest that patients with brain stem tumors demonstrating clinical and radiographic evidence of progressive tumor shortly after completion of HFR should be initially managed conservatively with dexamethasone, since these findings may be manifestations of reversible radiation related neurotoxicity. PMID- 1902548 TI - Outbreaks of diarrheal illness associated with cyanobacteria (blue-green algae) like bodies--Chicago and Nepal, 1989 and 1990. AB - Recent reports have described the detection of cyanobacteria (blue-green algae) like bodies (CLB) in the stools of persons with a prolonged syndrome of diarrhea, anorexia, and fatigue (1-3). In each of these reports, affected persons either were immunocompromised or had recently traveled to tropical countries. During 1989 and 1990, the first three reported outbreaks of this CLB-associated syndrome occurred in immunocompetent populations, affecting at least 150 persons. This report summarizes investigations of these outbreaks, which occurred in Chicago in 1990 and in Kathmandu, Nepal, in 1989 and 1990. PMID- 1902549 TI - [Use of a phage-plasmid vector for studying the expression of genes coding for the biosynthesis of threonine by Corynebacterium glutamicum in the mini-cell Escherichia coli system]. PMID- 1902550 TI - [Isolation and analysis of strains of Streptococcus faecium and Streptococcus bovis resistant to S-(2-aminoethyl)-L-cysteine]. PMID- 1902551 TI - [The molecular nature of Bacillus anthracis toxin]. AB - The biochemical nature of the three-component toxin of Bacillus anthracis is described as well as the molecular structure and regulation of the genetical determinants coding for its synthesis. The mechanism of toxin affect on animal cells is presented. The role of every of the toxin components in realization of Bacillus anthracis pathogenic properties is discussed. PMID- 1902552 TI - Recombinant factor VIII in hemophilia. PMID- 1902553 TI - Phosphorylation of two small GTP-binding proteins of the Rab family by p34cdc2. AB - Entry of a cell into mitosis induces a series of structural and functional changes including arrest of intracellular transport. Knowledge of how the mitotic cycle is driven progressed substantially with the identification of the p34cdc2 protein kinase as a subunit of maturation-promoting factor, the universal regulating component of the mitotic cycle. Activation of the kinase at the onset of mitosis is thought to trigger the important mitotic events by phosphorylating key proteins. Small guanine nucleotide-binding proteins have been implicated in regulating transport pathways. For instance, two small Ras-related GTP-binding proteins, Sec4p and Ypt1p, control distinct stages of the secretory pathway in budding yeast. The GTP-binding proteins of the Rab family in rats and humans display strong homologies with Sec4p and Ypt1p, and might therefore also be involved in regulating intracellular transport. Indeed, distinct Rab proteins are located in the exocytotic and endocytotic compartments. Interruption of vesicular transport during mitosis might involve modification of these proteins. We now present biochemical evidence for a mitosis-specific p34cdc2 phosphorylation of Rab1Ap and Rab4p. By contrast, Rab2p and Rab6p are not phosphorylated. We also show that the distribution of Rab1Ap and Rab4p between cytosolic and membrane bound forms is different in interphase and mitotic cells. This may provide a clue to the mechanism by which phosphorylation could affect membrane traffic during mitosis. PMID- 1902555 TI - Relationship of direct nursing care hours to DRG and severity of illness. AB - Great variation in nursing resource use is documented within DRGs. Much of this variation may be explained by patient severity of illness. Variance in nursing resource use within DRGs can be reduced by using a severity of illness instrument to score patients. PMID- 1902554 TI - Specific IgG activity of sera from Egyptian schistosomiasis patients to keyhole limpet hemocyanin (KLH). PMID- 1902556 TI - Looking above the bottom line: decisions in economic evaluation. AB - Economics can be a complex mix of formulae based on data with varying degrees of accuracy and assumptions. A realistic picture of costs and benefits will assist decision making and facilitate more accurate expectations and criteria for success. PMID- 1902557 TI - A longitudinal cost analysis of primary and team nursing. AB - Cost findings from a 4-year (1984-1989) externally funded, empirical study, comparing primary and team nursing on medical units in a tertiary care teaching hospital, demonstrates that primary nursing is less costly than team nursing. An average savings of 6.5% was realized for the duration of the study. Three factors are identified as being responsible for the difference on a cost per patient per day basis. Overall, cost analysis per DRG from primary nursing suggests cost differences related to high DRG volume and average length-of-stay. An administrative review of the study's implications highlights the relevancy of these findings in relationship to nurse retention and cost savings. PMID- 1902558 TI - [Histological diagnosis of brain tumors: (15). Pineocytoma, pineoblastoma]. PMID- 1902559 TI - Effects of carotenoid administration on bladder cancer prevention. AB - Bladder cancer was induced in male B6D2F1 strain mice by the administration of N butyl-N-(4-hydroxybutyl)nitrosamine. Mice supplemented with beta-carotene for 5 weeks before receiving the carcinogen and maintained on beta-carotene for an additional 26 weeks developed significantly fewer tumors than did unsupplemented mice. Mice receiving canthaxanthin for the same time period showed no protection against the development of bladder cancer. PMID- 1902560 TI - Effect of canthaxanthin on chemically induced mammary carcinogenesis. AB - Canthaxanthin, a carotenoid with no vitamin A activity, was evaluated for its efficacy in the prevention of chemically induced mammary cancers. Canthaxanthin was administered in the diet at two dose levels (3,390 or 1,130 mg/kg diet). In the dimethylbenzanthracene-induced mammary cancer model, diet supplementation with canthaxanthin for 3 weeks prior to the carcinogen resulted in a 65% reduction in the number of mammary cancers. The feeding of canthaxanthin after the administration of methylnitrosourea had no significant effect on mammary carcinogenesis. These data demonstrate that canthaxanthin, at least in these models of mammary cancer, is active in preventing cancer initiation and not promotion. Analysis of tissues by high-pressure liquid chromatography revealed that canthaxanthin levels in the liver are very high when compared to those in the mammary gland. The observation that canthaxanthin is highly effective in preventing cancer initiation without toxicity suggests that carotenoids not possessing vitamin A activity should be further evaluated as chemopreventive agents. PMID- 1902561 TI - Evaluating syringe drivers. PMID- 1902562 TI - A method to study drug concentration-depth profiles in tissues: mitomycin C in dog bladder wall. AB - Determination of the depth of penetration of locally applied drug therapy and evaluation of possible mechanisms of drug transport require knowledge of drug concentration-versus-tissues depth profiles. A method to determine the drug concentration-depth profile is needed. We have devised such a method and used it to determine the penetration of mitomycin C (MMC) in the dog bladder wall after intravesical drug instillation. This method is based on sectioning of frozen tissue into 40-microns segments, followed by drug extraction and high-pressure liquid chromatography analysis. Tissue concentrations could be detected with a sensitivity of 1 ng/sample, or 20 ng/g for tissue samples of approximately 2 x 2 cm. This sensitivity was sufficient to describe the penetration of MMC in the bladder wall of dogs, using an identical instillation technique, dwell time, and MMC concentration as in human patients. Tissue concentrations were expressed relative to tissue weight or tissue protein contents. For MMC, standardization to tissue weight yielded a better mathematical fit of the concentration-versus-depth profiles than standardization to protein content. The time interval between tissue harvesting and freezing was critical. The MMC concentration at the urothelial side of dog bladders was 2- to 10-fold higher in samples processed immediately after harvesting, compared to samples processed after 1 hr or longer. This significant decrease was not due to drug metabolism in situ. In separate in vitro experiments, we found that the degradation of MMC in 8% tissue homogenate was relatively slow, with only a 30% decline in concentration over 24 hr.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1902563 TI - In vitro release profile of mitomycin C from albumin microspheres: extrapolation from macrospheres to microspheres. AB - To analyze the in vitro release profiles of mitomycin C from albumin microspheres prepared by chemical denaturation in a multiparticulate system, a method to calculate the total cumulative amount of mitomycin C released from a batch of microspheres was developed. Mitomycin C-loaded albumin macrospheres (diameter in mm range) were prepared, and the in vitro release kinetics of mitomycin C from individual macrospheres were determined. Then the relationship between the kinetic parameters and the physical parameters (e.g., diameter, weight) was investigated under the assumption that macrospheres and microspheres behave identically. Further, the size distribution of microspheres was measured, and the total cumulative amount of mitomycin C released from albumin microspheres was calculated. The release profiles of mitomycin C from individual macrospheres fitted first-order release kinetics better than spherical matrix kinetics. The calculated initial mitomycin C contents and first-order release rate constants for individual macrospheres were correlated with the weight and reciprocal of surface area of the macrospheres, respectively. The observed in vitro release profile for the microspheres agreed with the calculated values. These results suggest that this method is valid for calculating drug release from albumin microspheres. PMID- 1902564 TI - Protection against microcystin-LR-induced hepatotoxicity by Silymarin: biochemistry, histopathology, and lethality. AB - Microcystin-LR, a cyclic heptapeptide synthesized by the blue-green algae, Microcystis aeruginosa, is a potent hepatotoxin. Pathological examination of livers from mice and rats that received microcystin-LR revealed severe, peracute, diffuse, centrilobular hepatocellular necrosis, and hemorrhage. These changes were correlated with increased serum activities of sorbitol dehydrogenase, alanine aminotransferase, and lactate dehydrogenase. Pretreatment of either rats or mice with a single dose of silymarin, a flavonolignane isolated from the wild artichoke (Silybum marianum L. Gaertn), completely abolished the lethal effects, pathological changes, and significantly decreased the levels of serum enzymes induced by microcystin-LR intoxication. PMID- 1902565 TI - Identification of LRF-1, a leucine-zipper protein that is rapidly and highly induced in regenerating liver. AB - Liver regeneration provides one of the few systems for analysis of mitogenesis in the fully developed, intact animal. Several proteins have been identified as part of the primary growth response in regenerating liver and in mitogen-stimulated cells. Some of these proteins, such as the Jun and Fos families of transcription factors, are thought to have a role in activating transcription of genes expressed subsequently in the growth response. Through differential screening of a regenerating-liver cDNA library, we have identified a rapidly and highly induced gene encoding a 21-kDa leucine-zipper-containing protein that we have designated liver regeneration factor 1 (LRF-1). LRF-1 has no homology with other leucine-zipper proteins outside the basic and leucine-zipper domains. LRF-1 alone can bind DNA, but it preferentially forms heteromeric complexes with c-Jun and Jun-B and does not interact with c-Fos. In solution, it binds with highest affinity to cAMP response elements but also has affinity for related sites. In cotransfection studies, LRF-1 in combination with c-Jun strongly activates a c Jun-responsive promoter. The induction of the LRF-1 gene in regenerating liver greatly increases the potential variety of heterodimeric combinations of leucine zipper transcription factors. While LRF-1 mRNA is rapidly induced in the absence of protein synthesis, its peak induction is later than c-fos mRNA, suggesting that LRF-1 may regulate responsive genes at a later point in the cell cycle. As such, LRF-1 may have a unique and critical role in growth regulation of regenerating liver and mitogen-stimulated cells. PMID- 1902566 TI - Analysis of the genes involved in the insulin transmembrane mitogenic signal in Chinese hamster ovary cells, CHO-K1, utilizing insulin-independent mutants. AB - CHO-K1 cells, wild type (WT), grow in a defined medium with insulin as the only essential hormone. When starved for insulin, these cells accumulate in G0/G1 stage. Insulin binding to its receptor stimulates DNA synthesis and cell division and induces an increase in abundance of mRNA for c-fos, c-jun, Krox-20, Krox-24 (zif/268), fra-1, jun-B, c-myc, and JE. The kinetics of induction of these genes are similar to that shown with serum induction of 3T3. These genes show maximum stimulation at insulin concentrations of 20, 160, or 320 ng/ml and their expression is inhibited at higher concentrations. The addition of cycloheximide results in superinduction. The WT and insulin-independent mutants show no detectable signal for KC, fos-b, or nur77 and no increase over the basal level of pI-15, probably eliminating these genes as participants in the insulin mitogenic signal. These mutants synthesize DNA in the absence of insulin at rates that vary from 4 to 12 times that of the quiescent (insulin unstimulated) WT and are further inducible by insulin. The mutants have "constitutive" levels of Krox-24 (zif/268), fra-1, jun-B, c-myc, and JE (INS-type 2 genes) mRNAs that vary from mutant to mutant, reaching a maximum of an 8-fold increase for fra-1 and JE over the quiescent WT levels. There were no detectable levels of mRNA for genes c-fos and Krox-20 and no increase in level of mRNA for c-jun (INS-type 1 genes) as compared to the quiescent WT. Thus, although these INS-type 1 and type 2 genes may be involved in the full insulin mitogenic signal, the constitutive up regulation of only genes in INS-type 2 is sufficient for insulin-independent DNA synthesis and cell division. Analysis of hybrids constructed between WT and mutant 27 indicate that the mutant phenotype is recessive, pointing to the existence of a regulatory gene producing a negative regulator. PMID- 1902567 TI - Neurotrophic protein S100 beta stimulates glial cell proliferation. AB - Nervous system development involves a coordinated series of events, including regulation of cell proliferation and differentiation by specific extracellular factors. S100 beta is a neurotrophic protein that has been implicated in regulation of cellular proliferation, but direct evidence was lacking. In this report, nanomolar concentrations of S100 beta are shown to stimulate proliferation of rat C6 glioma cells and primary astrocytes. An S100 mutant with a single amino acid change was inactive. S100 beta also stimulated increases in the steady-state levels of c-myc and c-fos protooncogene mRNAs and complemented the effects of platelet-derived growth factor. Two neuroblastoma cell lines did not proliferate in response to S100 beta, suggesting that the mitogenic activity of S100 beta is selective for astroglial cells. These results suggest that S100 beta may be involved in the coordinate development and maintenance of the central nervous system by synchronously stimulating the differentiation of neurons and the proliferation of astroglia. PMID- 1902569 TI - The mouse tyrosinase promoter is sufficient for expression in melanocytes and in the pigmented epithelium of the retina. AB - The mouse c locus encodes tyrosinase (monophenol monooxygenase; monophenol, L dopa:oxygen oxidoreductase, EC 1.14.18.1), the key enzyme in melanin synthesis, which is expressed in the pigment epithelium of the retina and in melanocytes derived from the neural crest. To define regulatory regions of the gene that are important for cell type-specific expression, a deletion series of the tyrosinase 5' region was fused to a chloramphenicol acetyltransferase (CAT) reporter gene and electroporated into tyrosinase-expressing and -nonexpressing cell lines. We show that 270 base pairs 5' of the transcriptional start site is sufficient for CAT expression in a human and a mouse melanoma cell line. This 5' flanking fragment, when cloned in the context of a tyrosinase minigene construct and injected into fertilized eggs of an albino mouse strain, is sufficient for cell type-specific expression in mice. The transgenic mice were pigmented in both skin and eyes. In situ hybridization analysis shows that the 270-base-pair regulatory region contains elements sufficient for specific expression of the transgene both in the pigmented epithelial cells of the retina, which are derived from the optic cup, and in neural crest-derived melanocytes. PMID- 1902568 TI - UGA is translated as cysteine in pheromone 3 of Euplotes octocarinatus. AB - Pheromone 3 mRNA of the ciliate Euplotes octocarinatus contains three in-frame UGA codons that are translated as cysteines. This was revealed from cDNA sequencing and from plasma desorption mass spectrometry of cleaved pheromone 3 in connection with pyridylethylation of the fragments. N-terminal sequence analysis of carboxymethylated protein confirmed this conclusion for the first of the three UGA codons. Besides UGA the common cysteine codons UGU and UGC are also used to encode cysteine. UAA functions as a termination codon. No UAG codon was found. In connection with results reported for other ciliates, this suggests that the role of the classic termination codons had not yet been established when the ciliates started to diverge from other eukaryotes. PMID- 1902570 TI - The Drosophila homologue of vertebrate myogenic-determination genes encodes a transiently expressed nuclear protein marking primary myogenic cells. AB - We have isolated a cDNA clone, called Dmyd for Drosophila myogenic-determination gene, that encodes a protein with structural and functional characteristics similar to the members of the vertebrate MyoD family. Dmyd clone encodes a polypeptide of 332 amino acids with 82% identity to MyoD in the 41 amino acids of the putative helix-loop-helix region and 100% identity in the 13 amino acids of the basic domain proposed to contain the essential recognition code for muscle specific gene activation. Low-stringency hybridizations indicate that Dmyd is not a member of a multigene family similar to MyoD in vertebrates. Dmyd is a nuclear protein in Drosophila, consistent with its role as a nuclear-gene regulatory factor, and is proposed to be a transiently expressed marker for muscle founder cells. We have used an 8-kilobase promoter fragment from the gene, which contains the first 55 amino acids of the Dmyd protein, joined to lacZ, to follow myogenic precursor cells into muscle fibers with antibodies to beta-galactosidase and to Dmyd. Unlike the myogenic factors in vertebrate muscle cells, Dmyd appears to be expressed at a much lower level in differentiated Drosophila muscles, so Dmyd cannot be followed continuously as a muscle marker. This fact is reflected in the loss of Dmyd RNA expression in 12- to 24-hr embryos, a major period of early myogenesis, as well as in the undetectable level of the nuclear antigen in primary cultures of embryonic and adult Drosophila muscle. PMID- 1902571 TI - Functional analysis of a liver-specific enhancer of the hepatitis B virus. AB - The liver-specific enhancer I of the human hepatitis B virus contains several regions of DNA-protein interaction. Located within this element are also the domains of a promoter controlling the synthesis of the X open reading frame. Functional domains of the enhancer I and the X gene promoter were identified using DNase I protection analysis, deletion mutagenesis, and cell transfections. A unique liver-specific interaction was identified within this element whose binding site includes a direct sequence repeat, 5'-AGTAAACAGTA-3'. The factor(s) binding to this sequence motif was purified by oligonucleotide-affinity chromatography. Binding of this factor appears to play a key role in determining the overall enhancer function. Additionally, the interaction of several purified factors is presented. Cotransfection of liver cells with expression vectors encoding transcriptional factors resulted in trans-activation of the promoter/enhancer function. Based on the results of genetic analysis a model outlining the functional domains of the enhancer/promoter region is presented. PMID- 1902573 TI - A post-transcriptional mechanism contributes to circadian cycling of a per-beta galactosidase fusion protein. AB - The period gene (per) of Drosophila melanogaster affects circadian rhythms. Circadian fluctuations in per mRNA levels are thought to contribute to circadian fluctuations in per protein levels in the heads of adult flies. To address the mechanisms underlying these oscillatory phenomena, we have analyzed RNA and protein cycling from two per-beta-galactosidase fusion genes. These studies demonstrate that 5' noncoding sequences from per are sufficient to cause the fusion mRNA levels to cycle in a wild-type (rhythmic) background. Protein cycling requires additional sequences derived from the per coding region. The data suggest that there is a per-dependent posttranscriptional mechanism that is under circadian clock control required for per protein levels to fluctuate in a rhythmic fashion. PMID- 1902572 TI - Dhr6, a Drosophila homolog of the yeast DNA-repair gene RAD6. AB - The RAD6 gene of the yeast Saccharomyces cerevisiae is required for DNA repair, for DNA damage-induced mutagenesis, and for sporulation, and it encodes a ubiquitin-conjugating enzyme. We have cloned the RAD6 homolog from Drosophila melanogaster and find that its encoded protein displays a very high degree of identity in amino acid sequence with the homologous RAD6 proteins from the two divergent yeasts, S. cerevisiae and Schizosaccharomyces pombe, and from human. Genetic complementation studies indicate that the Drosophila RAD6 homolog can functionally substitute for the S. cerevisiae RAD6 gene in its DNA-repair and UV mutagenesis functions but cannot substitute in sporulation. The high degree of structural and functional conservation of RAD6 in eukaryotic evolution suggests that the various protein components involved in RAD6-dependent DNA repair and mutagenesis functions have also been conserved. PMID- 1902574 TI - Nucleokinesis: distinct pattern of cell translocation in response to an autocrine motility factor-like substance or fibronectin. AB - Human lung adenocarcinoma cells develop bipolar shape with prominent pseudopodia (greater than or equal to 200 microns) when cultured in the presence of autocrine motility factor (AMF)-like substance or on fibronectin-coated substrata. AMF was partially purified from a human lung adenocarcinoma cell line and has a peak biological activity at a molecular mass of 67 kDa. Using time-lapse photography, we observed that during AMF- or fibronectin-induced cell translocation, the nuclei of some bipolar cells are transported to the opposite end of the cell, while gross cell shape and position remain unchanged. Following this nuclear movement, which we call "nucleokinesis," the posterior pseudopodium is retracted behind the nucleus. Thus, extension of a pseudopodium followed by nucleokinesis in the same direction and retraction of the cell body behind the nucleus is a normal motile sequence in translocating bipolar cells. This suggests that nucleokinesis is a distinct step in whole-cell translocation of bipolar cells on biological substrata and that pseudopodia can be used as nuclear transport organs. In contrast, adenocarcinoma cells cultured on artificial substrata and in the absence of AMF display a fibroblast-like motility pattern with the nucleus centrally located within the migrating cell. PMID- 1902575 TI - Guanine nucleotide-binding regulatory proteins in retinal pigment epithelial cells. AB - The expression of GTP-binding regulatory proteins (G proteins) in retinal pigment epithelial (RPE) cells was analyzed by RNA blot hybridization and cDNA amplification. Both adult and fetal human RPE cells contain mRNA for multiple G protein alpha subunits (G alpha) including Gs alpha, Gi-1 alpha, Gi-2 alpha, Gi-3 alpha, and Gz alpha (or Gx alpha), where Gs and Gi are proteins that stimulate or inhibit adenylyl cyclase, respectively, and Gz is a protein that may mediate pertussis toxin-insensitive events. Other G alpha-related mRNA transcripts were detected in fetal RPE cells by low-stringency hybridization to Gi-2 alpha and Gs alpha protein-coding cDNA probes. The diversity of G proteins in RPE cells was further studied by cDNA amplification with reverse transcriptase and the polymerase chain reaction. This approach revealed that, besides the above mentioned members of the G alpha gene family, at least two other G alpha subunits are expressed in RPE cells. Human retinal cDNA clones that encode one of the additional G alpha subunits were isolated and characterized. The results indicate that this G alpha subunit belongs to a separate subfamily of G proteins that may be insensitive to inhibition by pertussis toxin. PMID- 1902576 TI - Measurement of ligand-induced activation in single viable T cells using the lacZ reporter gene. AB - We have used the bacterial beta-galactosidase gene (lacZ) as a reporter gene for the rapid measurement of T-cell antigen receptor (TCR)-mediated activation of individual T cells. The reporter construct contained the lacZ gene under the control of the nuclear factor of activated T cells (NF-AT) element of the human interleukin 2 enhancer [Fiering, S., Northrop, J. P., Nolan, G. P., Matilla, P., Crabtree, G. R. & Herzenberg, L. A. (1990) Genes Dev. 4, 1823-1834]. The activity of the intracellular lacZ enzyme was analyzed by flow cytometric measurement of fluorescein accumulation in cells loaded with the fluorogenic beta-galactosidase substrate fluorescein di-beta-D-galactopyranoside. As a model system, the T-cell hybridoma BO4H9.1, which is specific for the lysozyme peptide (amino acids 74 88)/Ab complex, was transfected with the NF-AT-lacZ construct. lacZ activity was induced in 50-100% of the transfectant cells following exposure to pharmacological agents, to the physiological peptide/major histocompatibility complex ligand, or to other TCR-specific stimuli. Interestingly, increasing concentrations of the stimulus increased the fraction of lacZ+ cells, but not the level of lacZ activity per cell. Even under widely varying levels of stimulus, the level of lacZ activity in individual lacZ+ cells remained within a remarkably narrow range. These results demonstrate that TCR-mediated activation can be readily measured in single T cells and strongly suggest that, once committed to activation, the level of NF-AT transcriptional activity in individual T cells is independent of the form or concentration of stimulus. This assay is likely to prove useful for the study of early activation events in individual T cells and of TCR ligands. PMID- 1902577 TI - Human brain prostaglandin D synthase has been evolutionarily differentiated from lipophilic-ligand carrier proteins. AB - cDNAs for glutathione-independent prostaglandin D synthase were isolated from cDNA libraries of human brain. The longest cDNA insert was 837 base pairs long and contained a coding region of 570 base pairs corresponding to 190 amino acid residues with a calculated Mr of 21,016. Between two cDNA inserts isolated from the two different libraries, nucleotide substitutions were observed at 16 positions, including conservative amino acid substitutions at 2 positions and nonconservative substitutions at 5 positions, indicating genetic heterogeneity of this enzyme in humans. The computer-assisted homology search revealed that the enzyme is a member of the lipocalin superfamily, comprising secretory hydrophobic molecule transporters, showing the greatest homology (28.8-29.4% identity; 51.3 53.1% similarity) to alpha 1-microglobulin among the members of this superfamily. In a phylogenetic tree of the superfamily, this enzyme, alpha 1-microglobulin, and the gamma chain of the complement component C8 form a cluster separate from the other 14 members. The two distinctive characteristics of glutathione independent prostaglandin D synthase, as compared to the other members of this superfamily, are its enzymatic properties and its association with membranes that were probably acquired after evolutionary divergence of the two lipocalins. Based on the observed sequence homology, the tertiary structure of the enzyme was deduced to consist of an eight-stranded anti-parallel beta-barrel forming a hydrophobic pocket. Furthermore, the Cys-65 residue in the pocket, which is conserved only in the human and rat enzymes but not in other lipocalins, was considered to be a putative active site of the enzyme. PMID- 1902578 TI - Splicing of juvenile and adult tau mRNA variants is regulated by thyroid hormone. AB - The effect of thyroid hormone on the expression of tau transcripts was studied during postnatal brain development. The level of tau mRNA was only slightly changed postnatally in the cerebral hemispheres of hypothyroid rats, whereas the level of tau mRNA in the cerebellum was maintained at a higher level than in the euthyroid controls. As shown by in situ hybridization studies, such an alteration in tau mRNA expression can be ascribed to an effect of thyroid hormone on the rate of migration of the granule cells in the cerebellum; that tau mRNAs remain high in the cerebellum as long as the granule cells are migrating correlates with the observation that hypothyroidism slows the rate of migration of granule cells. RNase protection assays also showed that thyroid hormone deficiency delays the transition between the immature and mature tau transcripts in both brain regions. Thus, one of the effects of thyroid hormone is to regulate the splicing mechanism that allows replacement of the juvenile tau variants by the adult entities during neuronal differentiation. PMID- 1902579 TI - The Tariff's anomalies must be rethought. PMID- 1902580 TI - [Roles of phospholipid metabolism in cellular responses]. PMID- 1902581 TI - [Phospholipid metabolism during activation of human platelets--studies on the basis of phospholipid molecular species]. PMID- 1902582 TI - [Phospholipid metabolism in vascular endothelial cells]. PMID- 1902583 TI - [The metabolism of glycerophospholipids and its regulation of macrophages]. PMID- 1902584 TI - [Phospholipase C: its structure and molecular diversity]. PMID- 1902585 TI - [Phospholipase C activation and GTP-binding proteins]. PMID- 1902586 TI - [Phospholipid and atherosclerosis]. PMID- 1902587 TI - [Anti-tumor activity and anti-inflammatory action of organometal compound and inhibition of phospholipid metabolism]. PMID- 1902588 TI - [Anti-phospholipid antibodies and pathological conditions]. PMID- 1902589 TI - [Phospholipase D in signal transduction]. PMID- 1902590 TI - [Current developments in systemic therapy of breast carcinoma]. AB - New developments in hormone- and chemotherapy of metastasizing breast cancer comprise replacement of ovariectomy by LH-RH antagonists in premenopausal women, new antiestrogens with less residual estrogenic activity for use mainly in postmenopausal patients as well as new potent inhibitors of aromatase with fewer adverse effects also for postmenopausal women. These new drugs will possibly provide better efficacy with fewer side effects, but at higher cost. In chemotherapy the search for more potent regimes continues. Experiments are under way with high-dose chemotherapy plans in conjunction with autologous bone marrow transplantation and hemopoietic growth factors; however, the result of these latter studies are so far disappointing. It has become clear that in nonaggressive metastasizing cancer of the breast high rates of remission seem not to be the ultimate goal. At this stage of disease the natural course is very heterogeneous; therefore, chemotherapy has to be adapted to risk. The goal must be improvement of quality of life for the remaining life-span by palliation of symptomatic disease while inducing as few side effects of treatment as possible. New; more potent chemotherapeutic agents are not at sight. Research has recently produced derivatives of already known agents producing fewer adverse effects at equal efficacy. Decisive for the choice of primary chemotherapy are prognostic indicators of the disease. For most cases, tumor specific therapeutic modalities have to be optimized. PMID- 1902591 TI - Three-dimensional structure of recombinant human interferon-gamma. AB - The x-ray crystal structure of recombinant human interferon-gamma has been determined with the use of multiple-isomorphous-replacement techniques. Interferon-gamma, which is dimeric in solution, crystallizes with two dimers related by a noncrystallographic twofold axis in the asymmetric unit. The protein is primarily alpha helical, with six helices in each subunit that comprise approximately 62 percent of the structure; there is no beta sheet. The dimeric structure of human interferon-gamma is stabilized by the intertwining of helices across the subunit interface with multiple intersubunit interactions. PMID- 1902592 TI - In vivo footprinting of MHC class II genes: bare promoters in the bare lymphocyte syndrome. AB - Major histocompatibility complex (MHC) class II genes are coordinately regulated and show tissue-specific expression. With the use of in vivo footprinting, common promoter sites in these genes were found to be occupied only in cells that expressed the genes, in spite of the presence of the promoter binding proteins. In vivo analysis of mutant cell lines that exhibited coordinate loss of class II MHC expression, including several from individuals with bare lymphocyte syndrome, revealed two in vivo phenotypes. One suggests a defect in gene activation, whereas the other suggests a defect in promoter accessibility. PMID- 1902593 TI - Effect of light chain V region duplication on IgG oligomerization and in vivo efficacy. AB - A human immunoglobulin G1 (IgG1) antibody oligomer was isolated from a transfected myeloma cell line that produced a monoclonal antibody to group B streptococci. Compared to the IgG1 monomer, the oligomer was significantly more effective at protecting neonatal rats from infection in vivo. The oligomer was also shown to cross the placenta and to be stable in neonatal rats. Immunochemical analysis and complementary DNA sequencing showed that the transfected cell line produced two distinct kappa light chains: a normal light chain (Ln) with a molecular mass of 25 kilodaltons and a 37-kilodalton species (L37), the domain composition of which was variable-variable-constant (V-V-C). Cotransfection of vectors encoding the heavy chain and L37 resulted in production of oligomeric IgG. PMID- 1902594 TI - Portal vein thrombosis repermeabilization with rt-PA. PMID- 1902595 TI - Fibrinolytic activity in Chinese patients with diabetes or hyperlipidemia in comparison with healthy controls. AB - Plasma tissue-type plasminogen activator (tPA), plasminogen activator inhibitor (PAI) and euglobulin lysis time (ELT) were determined before and after the venous occlusion test (VOT) in 3 groups of patients with mean age about 60 years: 29 diabetic patients (D group), 8 hyperlipidemic patients (H group) and 19 healthy controls (C group). In the D and H groups, the mean of morning tPA was significantly higher than that of the C group, but the means of PAI were not significantly different among the 3 groups. ELT was significantly shortened and tPA was markedly increased after the VOT in all 3 groups whereas PAI had not significantly changed. In conclusion, high tPA activity and good fibrinolytic response without significant change of PAI activity were found in the diabetic and hyperlipidemic patients, and no definite impairment of the fibrinolytic activity could be found in the Chinese patients with diabetes and hyperlipidemia. This might be one of the reasons why the Chinese has low incidence of thromboembolic diseases. PMID- 1902596 TI - The influence of infusions of 1-desamino-8-D-arginine vasopressin (DDAVP) in vivo on the anticoagulant effect of recombinant hirudin (CGP39393) in vitro. AB - Hirudin is a specific, potent inhibitor of thrombin that may be a valuable antithrombotic agent. The aim of this study was to investigate the hypothesis that the haemostatic effects of DDAVP counteract the coagulation defect induced by hirudin. The effect of DDAVP was studied in vivo on the anticoagulant action of recombinant hirudin (CGP39393) in vitro. Blood samples were taken at intervals from 10 normal volunteers infused with DDAVP. Factor VIII:C rose from (mean) 0.68 IU/ml before DDAVP to 2.19 and 2.16 IU/ml after 30 and 60 min infusion, respectively. Samples taken during DDAVP infusion showed a dose related decrease in the hirudin (0.5 and 1.0 microM) induced prolongation of the APTT, that occurred at FVIII:C concentrations of up to twice normal. At higher concentrations of hirudin no effect on the APTT occurred. These results demonstrate that DDAVP infusion elevates factor VIII:C levels with an associated significant reduction in the anticoagulant effect of hirudin in vitro. PMID- 1902597 TI - Physical exercise induces enhancement of urokinase-type plasminogen activator (u PA) levels in plasma. AB - The enhancement of the blood fibrinolytic potential by physical exercise is generally attributed to the release of tissue-type plasminogen activator (t-PA) from the vessel wall. In this study we have investigated the possible contribution of urokinase-type plasminogen activator (u-PA). Six healthy male volunteers (age 21-25 years) were screened for their ability to perform maximal exercise for their age-group for 12 min on a bicycle ergometer. Subsequently, on one occasion they were required to remain supine for 2 h (from 8.30 a.m. onwards) an on another they performed maximal exercise (from 9.00 a.m. onwards). During exercise an increase in u-PA antigen and plasmin-activatable pro-urokinase (proUK) activity, concurrent with t-PA antigen and euglobulin t-PA activity, was observed in all six volunteers, while at rest these parameters remained unaffected. Mean u-PA- and t-PA antigen increased, respectively, from 4.2 +/- 1.0 ng/ml and 5.8 +/- 2.1 ng/ml before exercise to 9.8 +/- 3.0 ng/ml and 18.3 +/- 3.8 ng/ml (peak). Mean plasmin-activatable proUK activity and t-PA activity increased, respectively, from 2.1 +/- 0.4 ng/ml and 0.3 +/- 0.2 ng/ml before exercise to 4.3 +/- 1.7 ng/ml and 7.2 +/- 4.0 ng/ml (peak). The increases were statistically significant throughout (paired t-test, pre vs post, antigen P less than 0.005 and activity P less than 0.02). After cessation of exercise u-PA and t PA declined concurrently to normal values with a 50% decay in about 5 min.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1902598 TI - Blood-brain barrier disruption after cardiopulmonary resuscitation in immature swine. AB - We investigated blood-brain barrier permeability in 2-3-week-old anesthetized pigs during and after cardiopulmonary resuscitation. We assessed permeability by tissue uptake of radiolabeled aminoisobutyric acid, after correcting for plasma counts in tissue with radiolabeled inulin. Among 14 regions examined, the transfer coefficient of aminoisobutyric acid in nonischemic control animals ranged from 0.0018 +/- 0.0001 ml/g/min in diencephalon to 0.0049 +/- 0.0003 ml/g/min in cervical spinal cord. After 8 minutes of cardiac arrest followed by either 10 or 40 minutes of continuous sternal compression, there was no increase in the transfer coefficient. Likewise, during the immediate period after ventricular defibrillation, there was no increase in transfer coefficient despite the brief, transient hypertension. However, after 8 minutes of arrest, 6 minutes of cardiopulmonary resuscitation, and 4 hours of spontaneous circulation, the transfer coefficient was significantly increased by 59-107% in 10 of 11 regions rostral to the pons. Plasma volume in tissue measured by inulin was not elevated, suggesting that the increased transfer coefficient was not due to increased surface area. Thus, after an 8-minute period of complete ischemia, the blood brain barrier remains intact during and immediately after resuscitation despite large vascular pressure fluctuations. However, in contrast to previous work on adult dogs, immature pigs are prone to a delayed increase in permeability, thereby allowing circulating substances greater access to the brain. PMID- 1902599 TI - Selective attenuation by perivascular blood of prostanoid-dependent cerebrovascular dilation in piglets. AB - Cerebral hemorrhagic insults are common in neonates. However, the consequences of intracranial blood on cerebral hemodynamics are poorly understood. We examined the effects of perivascular blood on cerebrovascular dilator responses in 29 piglets. Fresh, autologous blood (n = 15) or cerebrospinal fluid (n = 14) was placed under the dura mater over the parietal cortex, and the piglets were allowed to recover from anesthesia. One to four days later, a closed cranial window was placed over the parietal cortex and pial arteriolar responses to arterial hypercapnia (PaCO2 greater than 55 mm Hg), hemorrhagic hypotension (mean arterial blood pressure less than 35 mm Hg), or topical application of 10(-6) and 10(-4) M isoproterenol were determined. Pial arterioles in the cerebrospinal fluid group dilated 27 +/- 4% (mean +/- SEM) (n = 11) in response to hypercapnia, 26 +/- 5% (n = 9) in response to hypotension, and 26 +/- 3% in response to 10(-6) M and 40 +/- 4% in response to 10(-4) M isoproterenol (n = 11). In the group in which blood was placed on the parietal cortex, pial arterioles did not dilate significantly in response to hypercapnia (8 +/- 3%, n = 11) or hypotension (2 +/- 5%, n = 13) but dilated normally in response to isoproterenol (25 +/- 5% in response to 10(-6) M and 36 +/- 7% in response to 10(-4) M, n = 13). We conclude that prolonged contact of pial arterioles with extravascular blood selectively attenuates cerebrovascular dilation in piglets. PMID- 1902601 TI - Description of a closed window technique for in vivo study of the feline basilar artery. AB - Recent interest in the regulatory functions of large cerebral arteries has led to many studies addressing the specific reactivity of these vessels. Current data originate mainly from in vitro experiments, as in vivo studies of larger intracranial cerebral arteries have been cumbersome so far due to the lack of a suitable animal model. We provide a detailed technical description of a closed transclival window method for in vivo study of the basilar artery in cats. We present our experience with this preparation in 29 animals, which shows that the technique is feasible and allows repeated, accurate, and reproducible measurements of the basilar artery, although possible depressive effects of the anesthesia on vascular reactivity have to be taken into account. With hyperventilation, the basilar artery constricted by 12.2 +/- 7.6% of the baseline diameter. The cerebral blood flow response to hypocapnia with this preparation was 2.0 +/- 0.4%/torr PaCO2. An exudative clouding of the window occurred in some cats but had no apparent effect on vascular reactivity. We also discuss possible pitfalls in the surgical preparation. PMID- 1902600 TI - Effects of insulin on blood, plasma, and brain glucose in hyperglycemic diabetic rats. AB - This study, in biologically bred hyperglycemic diabetic rats, examined the effect of a intravenous insulin infusion (1.5 units.hr-1) on blood, plasma, and brain glucose concentrations to determine their relationship during decreasing blood and plasma glucose levels. The data were compared to saline-treated diabetic rats and saline-treated nondiabetic littermates. The volume and duration of the treatment infusion were similar in all groups. Insulin infusion in diabetic rats produced the expected reduction in blood and plasma glucose, and normoglycemia was produced within 78 +/- 37 minutes (mean +/- SD). However, once normoglycemia was achieved, brain glucose was still significantly greater by 44% than in nondiabetic rats (p = 0.015). Moreover, the ratio of brain to plasma glucose was more than 50% greater in diabetic than nondiabetic rats, irrespective of whether or not they received insulin (p less than 0.01). We conclude that measurement of blood or plasma glucose in diabetic subjects will tend to underestimate the amount of glucose in the brain and that this relationship is not influenced by acute insulin therapy. PMID- 1902602 TI - [Occurrence of complement defects in meningococcal disease: who should be examined?]. AB - Congenital complement deficiency states occur very rarely. These deficiencies are associated with a high risk of meningococcal disease (MD). We suggest that the following groups of individuals with MD are examined for complement deficiencies: 1. Individuals belonging to families, in which more than one case of MD has occurred with an interval exceeding one month. 2. Individuals infected with the low-virulent meningococcal serogroups W-135, 29E, X, Y, Z. 3. Individuals with recurrent MD. Since properdin deficiency probably is the most common deficiency associated with MD it is important that the screening includes the alternative complement pathway. PMID- 1902603 TI - [Simultaneous measurement of end-diastolic pressure in the left ventricle and transmitral flow before and after nitroglycerin in patients with angina pectoris]. AB - In angina pectoris, left ventricular diastolic function evaluated by end diastolic pressure (LVEDP) on catheterization and transmitral flow (TMF) on Doppler echocardiography is abnormal. As a parameter describing TMF, the ratio between peak flow velocities of the two filling phases in diastole (PE/PA) can be used. We examined 22 patients with angina pectoris and measured LVEDP and PE/PA simultaneously and found positive correlation (r = 0.60). Nitroglycerin (0.8 mg sublingually) reduced LVEDP and PE/PA significantly, and correlation between reductions was positive (r = 0.52). None of the correlation analyses permitted LVEDP to be calculated from PE/PA, but Doppler echocardiography and TMF will probably be used increasingly in evaluation of ischemic heart disease with medical intervention. PMID- 1902604 TI - Urinary schistosomiasis with cutaneous lesions. AB - We report a case of urinary schistosomiasis with simultaneous presence of cutaneous lesions in a white male. The literature is reviewed, and the frequency, characteristics and physiopathology are discussed. PMID- 1902605 TI - Successful repair of huge bladder diverticulum with a transurethral fulguration. Report of a case. AB - We present a 68-year-old man with a huge bladder diverticulum associated with benign prostate hypertrophy treated with transurethral fulguration of the diverticular mucosa in combination with transurethral resection of the prostate. The procedure was well tolerated by the patient and unfavorable symptoms faded after this procedure. Follow-up cystogram demonstrated remarkable reduction of the diverticulum. PMID- 1902606 TI - Long-term observation after intravesical metaphylaxis with mitomycin C in patients with superficial bladder tumors. AB - After transurethral resection of a superficial bladder tumor 63 patients were treated by chemoprophylaxis with mitomycin C over a period of two years: 33.3 percent experienced recurrent disease under metaphylaxis and 42 patients who remained recurrence-free during instillation therapy were observed further for an average of 26.4 months. During this period 26.2 percent of the patients showed recurrences ranging between two to forty-four months after completing instillation. The majority of the patients in whom recurrent tumors developed also had recurrent tumor processes before the instillation therapy was begun. Of the 42 patients 73.8 percent stayed recurrence-free during the observation period of twelve to fifty-four months after completing instillation therapy. In conclusion, during an average observation period of 50.4 months, 52.4 percent of the patients in this study showed recurrences. PMID- 1902607 TI - [Alcoholism: definition, diagnosis, illness concept, follow-up, results and costs of treatment]. AB - The article starts with a review on the definition of alcoholism stressing the useful differentiation between alcohol abuse and alcohol dependence. On the basis of this definition the principles of the diagnosis of alcoholism are demonstrated. The disease concept of alcoholism is discussed in detail. Then the aims, the structure and the results of the therapy for alcoholics are briefly described. The article concludes with a short cost-benefit analysis of the alcoholism treatment. PMID- 1902608 TI - Activity of buparvaquone against Theileria cervi in white-tailed deer. AB - Buparvaquone, a naphthoquinone with known efficacy against Theileria parva parva in cattle, was tested for activity against Theileria cervi piroplasms in both an in vitro culture system and in vivo in experimentally infected white-tailed deer. The in vitro data showed a significant decrease in the incorporation of 3H hypoxanthine by infected red blood cells treated with buparvaquone when compared to that seen with imidocarb and chloroquine treatment. In both intact and splenectomized deer treated with buparvaquone (2.5 mg kg-1) a gradual decrease in piroplasm parasitaemia was observed following treatment. However, in the splenectomized deer, parasitaemia levels returned to near pretreatment values after approximately 2 weeks. PMID- 1902609 TI - Toxicity of cyst extract of Sarcocystis fusiformis from buffalo in rabbits and mice. AB - The toxic effect of cysts of Sarcocystis fusiformis (of buffalo origin) in rabbits and mice have been studied. It is shown that inoculation of a 2 mg ml-1 concentration of protein of the macrosarcocyst extract (ME) into rabbits and mice was lethal. The toxic substance was thermolabile at greater than or equal to 60 degrees C for 30 min. Protease and trypsin caused inactivation, while papain did not affect the toxicity. ME was found to be non-dialysable, but precipitable. There was also no effect of a pH of 6-9, while pH 4-5 altered the toxicity and pH 10 only partially affected the toxic effect. PMID- 1902610 TI - Unresponsiveness of vaccinated BALB/c mice to a second inoculation of lipopolysaccharide from Brucella abortus strain 2308. AB - A study was conducted to determine whether the protection induced in mice by a primary inoculation of lipopolysaccharide from Brucella abortus would be enhanced by a second inoculation given at different time intervals. Protection was challenged by exposure of the mice to a virulent culture of B. abortus strain 2308. Reduced mean viable count and/or splenic weights were the criteria of protection. There was no significant difference (P greater than 0.05) in the protective responses among mice given a single inoculation. Vaccinated mice were significantly (P less than 0.05) better protected than were nonvaccinated mice. Mice given vaccinal inoculations simultaneous with challenge exposure were less protected (P less than 0.001) than were mice vaccinated prior to challenge, but were better protected (P less than 0.010) than were nonvaccinated mice. PMID- 1902611 TI - Nitric oxide, nitrovasodilators, and L-arginine--an unusual relationship. PMID- 1902613 TI - Successful treatment of acquired factor VIII antibody by extracorporeal immunoadsorption. AB - We report the successful treatment of a 59-year-old woman with acquired factor VIII inhibitor. The patient who had an extensive leg hematoma with a resultant neurologic defect was treated with extracorporeal immunoadsorption (IA) using protein A-Sepharose, factor VIII concentrates, azathioprine, and methyl prednisolone. Extracorporeal IA reduced the titers of the inhibitor so that factor VIII concentrates could raise the level of factor VIII coagulant activity and stop the bleeding. PMID- 1902614 TI - Serum levels of CD8 antigen and soluble interleukin 2 receptors in patients with B cell chronic lymphocytic leukemia. AB - We assayed the plasma levels of CD8 antigen (CD8Ag) and soluble interleukin 2 receptor (sIL-2R) in 34 subjects with B cell chronic lymphocytic leukemia (B-CLL) and in 15 controls using an immunoenzymatic method. The results showed higher average levels of soluble CD8 (sCD8) and sIL-2R in the leukemic patients compared to the controls (sCD8 = 860 vs. 306 U/ml; sIL-2R = 4,131 vs. 311 U/ml). The two antigen levels were significantly higher in patients with progressive disease than in those with indolent disease, and they also correlated with Rai's stage. sIL-2R levels correlated with lymphocyte count (p less than 0.001), while there was no correlation between sCD8 levels and total number of lymphocytes. These results seem to show that the measurement of serum levels of CD8Ag and sIL-2R may be a useful tool in the prognostic evaluation of patients with B-CLL. PMID- 1902612 TI - Pharmacology of endothelium-derived nitric oxide and nitrovasodilators. AB - Nitric oxide is the active chemical species responsible for the vasodilator action of nitroglycerin, nitroprusside, and related nitrovasodilators. The most potent vasodilator and inhibitor of platelet aggregation known, nitric oxide was recently discovered to occur endogenously as the endothelium-derived relaxing factor. The pharmacology of endothelium-derived nitric oxide is virtually identical to that of the clinically used nitrovasodilators. Although endothelium derived relaxing factor or endothelium-derived nitric oxide seems to be important in animals, its significance in humans still needs to be shown. We review the recent discoveries in the identification, biosynthesis, metabolism, and biologic actions of endothelium-derived nitric oxide, its significance in humans, and its relation to the clinically used nitrovasodilators. PMID- 1902615 TI - Generation of arachidonic acid metabolites from stimulated whole blood in patients with chronic myeloproliferative disorders. AB - We have evaluated the arachidonic acid (AA) metabolism in patients with myeloproliferative disorders (MPD). In essential thrombocythemia (ET), the generation of thromboxane B2 was found significantly reduced and inversely correlated with platelet count. Polycythemia vera (PV) patients showed an increased formation of this metabolite of AA. Prostaglandin E2 and 6-keto-PGF1 alpha generation were markedly reduced in patients with chronic myelogenous leukemia. Our study confirms that the arachidonate metabolism is frequently deranged in patients with MPD. The opposite changes in thromboxane formation in ET and PV could be one of the factors responsible for the different incidences of thrombotic and hemorrhagic complications in these diseases. PMID- 1902616 TI - Cerebral vasoreactivity and the prediction of outcome in severe traumatic brain lesions. AB - Mean hemispheric blood flow (CBF) was studied in 38 comatose, severely brain injured patients following intravenous administration of xenon-133. Repeated measurements were performed in order to evaluate cerebral vasoreactivity following a decrease in PaCO2. Simultaneously, arterial-venous oxygen differences (AVDO2) and intracranial pressure (ICP) were measured. An impaired CBF response to hyperventilation (delta CBF/delta PaCO2 less than 1.0) was obtained in 22 patients. Three of 16 patients with preserved CO2-reactivity died because of their brain injuries and 12 patients reached good recovery/moderate disability. In the group of patients with impaired vasoreactivity 11 of 22 patients died and only three patients reached good recovery/moderate disability. The study documents that in patients with severe traumatic brain lesions measurements of cerebral vasoreactivity to hyperventilation give prognostic information that is not obtained by clinical observations or CT-scanning. PMID- 1902617 TI - Effects of acute alterations in left ventricular loading conditions on peak filling rate in the denervated (transplanted) ventricle. AB - Peak filling rate is an indicator of left ventricular (LV) diastolic function. It is influenced by heart rate, loading conditions, sympathetic nervous system activity, ejection fraction and other factors. To determine the effect of altered loading conditions on peak filling rate, independent of heart rate and sympathetic nervous system activity, 12 patients were studied 3 weeks after orthotopic heart transplantation. Plasma catecholamine level, heart rate and ejection fraction were not changed by any maneuver. Nitroglycerin caused a decrease in pulmonary artery wedge pressure (9 +/- 2 to 6 +/- 1 mm Hg, p less than 0.001) and in absolute peak filling rate (46.0 +/- 3.0 to 42.8 +/- 2.5 kcts/s, p less than 0.01), but no change in normalized peak filling rate. Volume infusion increased pulmonary artery wedge pressure (9 +/- 2 to 12 +/- 2 mm Hg, p less than 0.001) and absolute peak filling rate (46.0 +/- 3.0 to 51.5 +/- 5.3 kcts/s, p less than 0.01), but peak filling rate normalized to stroke volume was unchanged. During nitroglycerin and volume infusions, there was a high correlation between changes in pulmonary artery wedge pressure and absolute peak filling rate (r = 0.82, p less than 0.001). With normalization of peak filling rate, these variables correlated less well. With methoxamine, 4 patients demonstrating systolic dysfunction had a decrease in absolute and normalized peak filling rate despite a large increase in pulmonary artery wedge pressure. The other 8 patients without systolic dysfunction had an increase in pulmonary artery wedge pressure with increased absolute but unchanged normalized peak filling rate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1902618 TI - Prospective gene rearrangement studies and multiparameter analysis of acute myeloid leukemia. AB - Twenty-six cases of acute myeloid leukemia (AML) with cytochemical and immunophenotypic data were studied prospectively for immunoglobulin and T-cell receptor gene rearrangement. Dysmyelopoiesis was seen in 100% and Auer rods in 18%. Sudan black B was positive in 83% of the cases, peroxidase in 76%, nonspecific esterase in 74% (fluoride-inhibited in 82%), chloroacetate in 70%, acid phosphatase and PAS in 100%, and immunoperoxidase stains for platelet glycoprotein IIIa and factor VIII in 0% of the cases studied. Flow cytometry revealed myeloid phenotype in 19 of 20 cases. In four cases 5-86% of cells were TdT positive. Heavy-chain gene rearrangement was demonstrated in three cases (12%) and kappa light chain gene rearrangement in one; clinically significant rearrangement of the T-cell receptor gene was not found. Rearrangements of immunoglobulin genes are found occasionally in AML; these may represent nonspecific findings or coexistent lymphoid differentiation in AML. PMID- 1902619 TI - Platelet dysfunction in Noonan's syndrome. A case with a platelet cyclooxygenase like deficiency and chronic idiopathic thrombocytopenic purpura. AB - Individuals with Noonan's syndrome are likely to have one or more coagulation abnormalities: complex platelet function defects, partial Factor XI deficiency, or von Willebrand's disease. A distinctive platelet function defect has not been identified. The authors describe a 24-year-old women with Noonan's syndrome, chronic idiopathic thrombocytopenic purpura (ITP), and a platelet function defect characterized by a greater than 15-minute bleeding time, failure of aggregation and release with 10 microM ADP, 10 microM epinephrine, 750 microM arachidonic acid or 0.019 g/L collagen. A mixture of aspirin-treated platelets with the patient's platelets failed to correct the defect. Addition of 2.5 microM U46619 (a PGG2 analogue) corrected the aggregation and release defect. An electron microscopic analysis failed to reveal structural abnormalities. Thus, the platelet function defect in this patient appears to be a functional deficiency of cyclooxygenase. The presence of autoantiplatelet antibodies in a clinical setting consistent with chronic ITP raises the possibility that the defect may be acquired. PMID- 1902620 TI - Computer-assisted work station timing analysis of instrument labor efficiency. AB - Labor use ratings assigned to instruments by the Workload Recording Method (WRM) do not change with batch size or walk-away time use. The authors evaluated the effect of both on the labor use of the analyzers Paramax B6100 (Baxter Paramax, Irvine, CA) and Ektachem 700 (Eastman Kodak, Rochester, NY) by timing all worked and walk-away intervals on both instruments. Extrapolation of the data to a workload of slightly more than 1.1 million tests showed that reapportionment of tests to various batch sizes caused Paramax-Ektachem labor cost differences to fluctuate between $37,254 and $34,995. When the minimum usable walk-away interval length was varied from 1 to 20 minutes, Ektachem savings over Paramax increased from $8,700 to $61,400. The WRM predicted a constant $29,050 labor cost advantage for Ektachem over Paramax. If other instruments show similar labor use characteristics with respect to batch size and walk-away utility, laboratory managers who do not consider these factors may fail to select the most cost effective instruments for their laboratories. PMID- 1902621 TI - Simultaneous occurrence of factor VIIIC inhibitor and antinuclear antibody in postpartum period. AB - We are describing a rare case of acquired factor VIIIC inhibitor in postpartum period who also had strongly positive antinuclear antibody. On immunosuppression with prednisolone and azathioprine, both antibodies disappeared after 4 months of therapy. PMID- 1902622 TI - Erythrocyte Webb-type glycophorin C variant lacks N-glycosylation due to an asparagine to serine substitution. AB - We have analyzed part of the sequence of the human glycophorin C (GPC) gene carried by a Webb blood-group positive donor. Our results indicate that the lack of N-glycosylation of the variant GPC associated with the Webb phenotype is due to a point mutation resulting in an asparagine to serine substitution at amino acid position 8. PMID- 1902623 TI - Disturbances in the tissue plasminogen activator/plasminogen activator inhibitor (TPA/PAI) system in systemic lupus erythematosus. AB - Increased thrombogenesis observed in systemic lupus erythematosus (SLE) is derived from multiple mechanisms, including: Enhanced coagulation factor VIII:VWf activity, lupus anticoagulants, anti-phospholipid antibodies, acquired deficiencies of natural anti-thrombotic mechanisms (protein C, protein S, anti thrombin III), and impaired fibrinolytic mechanisms. We studied the fibrinolytic mechanisms of 18 patients with systemic lupus erythematosus, selected carefully to avoid other possible causes of abnormalities in the fibrinolytic activity. Despite the fact that the euglobulin lysis time in steady state was normal in all instances, disturbances in the tissue plasminogen activator/plasminogen activator inhibitor (TPA/PAI) system were found in all SLE patients: TPA activity was undetectable in all cases, whereas it was above 0.4 IU/ml in a control group. In 72 percent of patients, the undetectable TPA activity was correlated with abnormally high PAI activity; PAI levels were normal in all members of the control group, their mean value being 0.74 versus 8.63 IU/ml for SLE patients (P less than .01). Coagulation protein C deficiency was found in 3 patients (17%). Even though within normal range, fibrinogen levels were significantly higher in SLE than in normal controls (219 versus 192 mg/dl, P less than .01) and plasminogen levels were significantly higher in SLE than in controls (117 versus 78.2%, P less than .01). Cross-linked fibrin derivatives (D-D dimers) were negative in all patients with SLE. Sixty-eight percent of SLE patients had high levels of antiphospholipid antibodies, but no correlation with the disturbances of the TPA/PAI system was found. It is concluded that most patients with SLE display severe abnormalities in the TPA/PAI anti-thrombotic system and that these abnormalities may be related to the lupus thrombophilia, apparently multifactorial in its origin. PMID- 1902624 TI - Alterations of polymorphonuclear leukocyte glycogen metabolism and glucose uptake in dialysis patients. AB - Human polymorphonuclear leukocytes (PMNs) are activated during extracorporeal circulation. An indicator of PMN activation may be the glycogen-degrading enzyme phosphorylase. It is unknown whether dialysis therapy may influence PMN carbohydrate metabolism. Therefore, PMNs were isolated from healthy control subjects, patients undergoing continuous ambulatory peritoneal dialysis (CAPD), and patients undergoing regular hemodialysis therapy (RDT) before, during, and at the end of hemodialysis (HD) treatment using dialyzers made of polysulfone or polymethylmethacrylate (PMMA). Nifedipine (NIF) was continuously infused during HD with PMMA in 5 patients at a dose of 18 micrograms/kg body weight per hour. Glycogen, activity of glycogen synthetase and phosphorylase (active and inactive forms of both enzymes), and glucose uptake with and without stimulation with the chemotactic peptide FMLP were determined in these PMNs. During HD with PMMA, there was a significant increase of PMN phosphorylase "a" activity 15 and 30 minutes after the start of HD. HD with polysulfone did not stimulate the active "a" form of the glycogen-degrading enzyme in PMNs. HD with PMMA significantly inhibited the active I-form of glycogen synthetase, whereas polysulfone activated glycogen synthetase I. NIF inhibited phosphorylase "a" activation during HD with PMMA. PMN glycogen content and glucose uptake were improved during HD with polysulfone, but not with PMMA. PMN glycogen content, activity of glycogen synthetase, and glucose uptake were significantly lower also in CAPD patients compared with healthy controls. These data show that HD with PMMA activates PMN glycogenolysis. This effect can be inhibited by calcium channel blockers. PMN glycogen content of RDT and CAPD patients is significantly lower compared with healthy controls due to inhibition of glycogen synthesis. Elimination of dialyzable factor(s) improves, but does not restore, PMN glycogen synthesis and glucose uptake. PMID- 1902625 TI - Troubleshooting your tube feedings. PMID- 1902626 TI - Importance of viability and attachment to an ascites tumor in the release of plasminogen activator. AB - Tumor plasminogen activator (PA) has been alleged to play a role in the growth and metastasis of tumors. Before such a role can be realized, PA first must be released from tumor cells. Having determined intra- and extracellular PA and PA inhibitor activities in an experimental pancreatic ascites tumor grown in hamsters, the release of PA from these cells was investigated. No PA activity was detected in the suspension medium of freshly isolated tumor cells; inclusion of plasminogen, fibrinogen, or collagen in the medium yielded similar negative results. On the other hand, PA activity was demonstrated to be released in a time dependent manner from these tumor cells embedded in fibrin clots. Plasminogen activator activity also was not found in the suspension medium of frozen-thawed tumor cells, despite the fact that most of them had breaks on their cell membrane. Unlike freshly isolated tumor cells, PA was not released from frozen thawed cells embedded in fibrin clots. Full PA activity was demonstrated in frozen-thawed cells treated with Triton X-100, however. Frozen-thawed cells exhibited signs of severe damage, and more than 80% of them failed to exclude trypan blue. Obviously PA is released from viable tumor cells embedded in fibrin clots but not suspended in artificial medium. The PA-release mechanism, not PA itself, is destroyed in cells rendered nonviable by freeze thawing. PMID- 1902627 TI - Activation of intraislet lymphoid cells causes destruction of islet cells. AB - In vitro culture of rat islets at 24 degrees C for 7 days in tissue culture medium CMRL 1066 almost completely eliminated lymphoid cells from the islets. Immunostaining of the islets with monoclonal antibody OX4 for demonstration of class II major histocompatibility complex (MHC)-expressing cells revealed a decrease from 13.1 +/- 0.6 positive cells per islet on day 0 to 0.7 +/- 0.1 cells per islet on day 7. A comparable decrease was found using OX1 for demonstration of all leukocytes. In contrast, culture of rat islets at 24 degrees C for 7 days with tissue culture Roswell Park Memorial Institute (RPMI) 1640 medium was not as effective in eliminating lymphoid cells as in medium CMRL 1066 (3.0 +/- 0.2 class II MHC positive cells per islet at 7 days). Effective elimination of intraislet lymphoid cells apparently is due to the combined effect of low temperature culture and the tissue culture medium CMRL-1066. The second goal of the study was to determine whether the destructive effect of interferon gamma (IFN-gamma) on rat islets in culture was due to intraislet lymphoid cells. In vitro culture of rat islets with IFN-gamma (1000 units/ml) at 37 degrees C caused almost complete destruction of the islets at 7 days. If intraislet lymphoid cells were eliminated from the islets by in vitro culture at 24 degrees C followed by exposure to IFN gamma (1000 units/ml) for 7 days at 37 degrees C, then IFN-gamma did not cause destruction of the islets and transplants of the treated islets produced normoglycemia in diabetic recipient mice. These findings indicate that intraislet lymphoid cells are responsible for destruction of islet cells when these cells (presumably macrophages) are activated by IFN-gamma. Intraislet lymphoid cells may play a significant role in destroying islet cells in autoimmune diabetes. PMID- 1902629 TI - Disposable carbon dioxide detectors. PMID- 1902628 TI - Reproductive factors affecting survivorship in captive Callitrichidae. AB - Efforts to breed Callitrichidae in captivity have resulted in high fertility accompanied by high infant mortality. This paper investigates the relationship between reproductive characteristics and survivorship in the Oak Ridge and Associated Universities (ORAU) callitrichid colony. Records of 2,834 individuals were analyzed using Cox Proportional Hazards regression to investigate factors affecting infant survivorship. Species and birth cohort were found to have a significant (P less than 0.05) effect on survivorship. Litter size also was an important factor in determining survivorship. Individuals born into singlet and twin litters had significantly (P less than 0.001) higher survivorship than triplets. Factors which affect survivorship perinatally (0-1 months of age), prior to breeding age and subsequent to the first month of life were then investigated. Litter size was a significant (P less than 0.05) factor in determining survivorship perinatally, with twins having significantly higher survivorship than both singlets and triplets. After the first month of life, litter size no longer showed a significant effect on survivorship. Records of 145 dams were analyzed using the same procedures to investigate reproductive characteristics associated with survivorship. Age at first litter showed a significant (P less than 0.01) positive relationship with dam survivorship. These results suggest various factors affect survivorship at specific temporal points during development, and also suggest selection for survivorship perinatally to be strongly associated with litter size, possibly through sibling competition and maternal effects. PMID- 1902630 TI - Spermiation and sperm maturation in the marmoset. AB - The scanning and transmission electron microscopes were used to examine the processes of spermiation and sperm maturation in the marmoset. We observe that the heads of late spermatids are embedded in the apical aspect of the large sleeve-like columnar portion of Sertoli cells. As spermiogenesis progresses, spermatids become associated with numerous small apical Sertoli cell extensions. These finger-like processes undergo a sequence of changes during spermiation. Spermatozoa from the caput, corpus, and cauda epididymides were examined. In caput epididymis of marmoset, the apical segment of the spermatozoa extends well beyond the rostral edge of the nucleus and folds back on itself. In sagittal sections, the acrosome exhibits a distinct hook shape. In the corpus, the distinctive hook-shaped apical segment of the acrosome is observed in some spermatozoa, but the apical extension is significantly smaller or projects out only slightly beyond the nucleus. In cauda epididymis, the extension is absent. A similar acrosomal hook has been reported in the pigtailed monkey, which is an Old World species. We suggest that changes in acrosome structure during sperm maturation may be fairly widespread among primates. PMID- 1902631 TI - Cellular distribution of inhibin in marmoset testes during development. AB - Using polyclonal antibodies against a 13 KD human testicular inhibin, immunocytochemical localization studies were carried out in marmoset monkey testes. The pattern as well as the intensity of immunocytochemical staining for inhibin vary substantially during development. In early development (day 1 to 2 months) Leydig cells are the predominant cell types showing intense staining which reaches its nadir at 3 months. Subsequently both Sertoli cells as well as Leydig cells show equal intensity of inhibin staining. Testicular inhibin is likely to play a vital role in cell to cell communication. PMID- 1902632 TI - Lack of evidence for a percent saturation gap in cyanide poisoning. AB - STUDY OBJECTIVES: To determine if toxic concentrations of cyanide in blood result in a difference between calculated and measured percent hemoglobin oxygen saturation (percent saturation gap). DESIGN: An in vitro laboratory study. SETTING: Hospital laboratory. TYPE OF PARTICIPANTS: Arterial blood from five stable patients residing in a tertiary hospital ICU. Venous blood samples obtained from five healthy volunteers. INTERVENTIONS: Two-mL aliquots from each blood sample were placed into four test tubes and mixed with phosphate buffer. Cyanide was added to three of the tubes so that the four tubes contained 0, 6, 12, and 25 mg/L cyanide. MEASUREMENTS AND MAIN RESULTS: The percent saturation gap was calculated by subtracting the percent oxyhemoglobin measured on an oximeter from the percent saturation calculated by a blood gas analyzer. Using two-tailed, paired t tests, we could not demonstrate a difference in mean percent saturation gaps between arterial samples or venous samples with and without cyanide. All blood samples had a normal percent saturation gap (P greater than .99 by Fisher's exact test). We had greater than a 95% chance of demonstrating a difference in mean percent saturation gaps of only 0.46% in arterial blood and of 3.3% in venous blood if such a difference existed. CONCLUSIONS: Our results, as well as a review of the literature, indicate that there are no data supporting the suggestion that a percent saturation gap should imply the diagnosis of poisoning by inorganic cyanide. PMID- 1902633 TI - Acute misoprostol toxicity. AB - Misoprostol (Cytotec) is a recently released prostaglandin E1 analog approved for use in prevention of nonsteroidal anti-inflammatory drug-induced gastropathy. We report one of the first known examples of toxicity in an acute ingestion since the drug was first released in international markets in 1984. After an accidental ingestion of 3 mg misoprostol (approximately 15 times the maximum recommended therapeutic dose), a 71-year-old woman exhibited fever, tremor, tachycardia, hypertension, nausea, and abdominal cramping. Recovery ensued with standard supportive care. The physiology of this unique drug and implications for management of acute toxicity are summarized. PMID- 1902634 TI - Pharmacologic control of plasma exudation into tracheobronchial airways. AB - We have employed anesthetized guinea pigs to examine effects of nonsteroidal antiasthma drugs on airway plasma exudation, which is a process of potential pathogenetic importance in asthma. This study focused on exudation of plasma into the airway luman (circumventing problems with a changing blood pool in tissue samples). Topical tracheal superfusions with a neurogenic agent (capsalcin), bradykinin, and histamine increased mucosal blood flow (Laser Doppler flowmetry) and produced significant exudation of macromolecular plasma tracers (fluorescein labeled dextran 156000 D; 131I-albumin 70,000 D). Lidocaine 3 x 10(-5) M, applied topically, inhibited capsalcin- but not bradykinin-induced plasma exudation. Intravenously administered terbutaline, enprofylline, and theophylline and topical cromoglycate dose-dependently inhibited the inflammatory stimuli-induced mucosal exudation of plasma. Cromoglycate did not alter airway blood flow, and both terbutaline and enprofylline increased the blood flow. Hence, these three types of drugs did not inhibit exudation by stopping flow. Further, both neural and non-neural exudative responses were inhibited, suggesting that the drugs may have acted directly on the permeability-regulating microvascular endothelial cells. It is proposed that antiexudative actions may contribute to the antiasthma effects of beta 2-agonists, xanthines, and cromoglycates. PMID- 1902636 TI - Acute lung injury induced by phospholipase A2. Structural and functional changes. AB - On the basis of the observation that serum levels of phospholipase A2 (PLA2) are elevated in pancreatitis and systemic sepsis, and the association of these conditions with the subsequent development of acute lung injury, the present investigation examined the structural and physiologic consequences of intratracheal administration of PLA2 to adult male rats. Rats received direct intratracheal instillation of either control vehicle or 40,000 units/kg of PLA2 repurified from Naja naja venom. Animals treated with PLA2 showed higher cumulative mortality (33% versus 0%, n = 79; p less than 0.01) than did their control littermates. The PLA2-treated animals showed histologic evidence of acute lung injury characterized by interstitial and alveolar edema, accumulation of inflammatory cells, and alveolar wall thickening, which reached maximal severity 48 h after enzyme instillation. Forty-eight hours after PLA2 administration experimental animals had lower arterial oxygen tensions (73.9 +/- 7.66 mm Hg versus 96.7 +/- 2.52 mm Hg, mean +/- SEM; p less than 0.01), higher alveolar arterial oxygen gradients (35.3 +/- 6.3 mm Hg versus 18.8 +/- 1.42 mm Hg, p less than 0.01), and higher wet-dry lung weight ratios (5.08 +/- 0.26, mean +/- SEM, n = 7 versus 3.29 +/- 0.08, n = 3; p less than 0.002) than did control animals. Lung lavage from experimental animals 48 h after PLA2 instillation showed increased total cell counts [(26.6 +/- 5.04) x 10(6) cells versus (4.69 +/- 1.48) x 10(6) cells; p less than 0.01], an increased percentage of neutrophils (34.2 +/ 4.6% versus 1.25 +/- 0.25%, mean +/- SEM; p less than 0.01), and increased protein concentrations in lavage fluid (0.38 +/- 0.06 mg/ml, mean +/- SEM, n = 4 versus 0.27 +/- 0.02 mg/ml, n = 5; p less than 0.05). The histologic and physiologic abnormalities had largely resolved by 240 h. These results suggest that PLA2 may be a potent mediator of lung inflammation and that intratracheal administration of PLA2 to adult rats may provide a useful experimental model of acute lung injury. PMID- 1902635 TI - Defective candidacidal activity of alveolar macrophages and peripheral blood monocytes from patients with chronic obstructive pulmonary disease. AB - We investigated the in vitro candidacidal activity of alveolar macrophages (AM) and peripheral blood monocytes (PBM) from normal subjects or from patients with chronic obstructive pulmonary disease (COPD) displaying defective skin test delayed-type hypersensitivity (DTH) reactivity to seven antigens including Candida albicans. The results showed that cells from patients with COPD were significantly less effective than cells from control subjects in the killing of C. albicans. To explore whether the observed functional impairment could be reversed, interferon-gamma (IFN-gamma) was added to AM and PBM from patients with COPD, alone or in the presence of lipopolysaccharide (LPS) as a suboptimal stimulus. The cells were cultured for 24 h and then assayed for anti-Candida activity. After IFN-gamma treatment, the fungicidal activity of cells from patients with COPD was comparable to that of unstimulated AM or PBM from healthy donors. Treatment with IFN-gamma plus LPS resulted in a further enhancement in the killing of C. albicans. To gain more insight into the mechanisms involved in the modulation of killing, we evaluated the possible stimulating activity of IFN gamma plus LPS treatment on the secretion of tumor necrosis factor (TNF) and interleukin-1 (IL-1), two cytokines produced by activated macrophages and capable of stimulating natural effectors. The results showed that IFN-gamma plus LPS can indeed stimulate TNF and IL-1 secretion by AM and PBM from patients with COPD. Therefore, a precise role can reasonably be ascribed to these soluble factors in the observed augmentation of candidacidal activity as ascertained by treatment with IFN-gamma plus LPS. PMID- 1902637 TI - Elimination of Staphylococcus aureus carriage. PMID- 1902638 TI - Factor VIII replacement therapy. Issues and future prospects. PMID- 1902639 TI - Endothelial cell fibrinolytic assembly. AB - Endothelial cells play a critical role in thromboregulation by controlling the assembly of fibrinolytic constituents on the membrane. The assembly system illustrated in FIGURE 6 is characterized by the binding of circulating glu plasminogen to a membrane receptor (Pathway 1). A membrane-associated protease (possibly plasmin) converts the inactive zymogen into a catalytically more efficient zymogen lys-plasminogen (Pathway 2). T-PA binds to a specific receptor, retains its catalytic activity, and is protected from its natural inhibitor PAI 1. The membrane provides a favorable environment for plasmin generation (Pathway 3) at the vessel surface and contributes to the maintenance of a physiological nonthrombogenic state. The immobilization and surface activation of plasminogen provides an important mechanism for localizing proteolytic activity at the surface of other cells such as macrophages and tumor cells. Lp(a), a plasminogen like lipoprotein, by competing at the endothelial surface for plasminogen binding down-regulates endothelial cell plasmin generation and may thus promote localized thrombogenesis that over a period of time contributes to progressive atherosclerosis. PMID- 1902640 TI - Thrombolytic therapy. PMID- 1902641 TI - Factor VIII structure and function. PMID- 1902642 TI - The molecular basis of hemophilia A. AB - Due to new, sensitive methodologies, the rate at which factor VIII gene mutations are found is increasing rapidly. The next five years should lead to the discovery of a wide range of defects as well as potential new hot-spots for mutations. Advances in understanding the protein will also provide new insights into the effects of particular mutations. Tremendous strides have been made in carrier detection and prenatal diagnosis. Already diagnosis is possible in 70% of cases with the factor VIII intragenic polymorphisms. Although there is still room for improvement in availability, speed, and cost of the test, many families in the United States and Europe are benefiting from this sensitive detection method. PMID- 1902643 TI - Complications of hemophilia A treatment: factor VIII inhibitors. PMID- 1902644 TI - Altered effect of arachidonic acid on inner ear blood flow in rats with streptozotocin-induced diabetes. AB - The present study was undertaken to clarify the altered effect of arachidonic acid on inner ear blood flow in rats with streptozotocin-induced diabetes by use of the laser-Doppler flowmeter. Drugs were administered intraarterially via the subclavian artery in a dose range that did not affect the systemic blood pressure. Both arachidonic acid and papaverine hydrochloride increased inner ear blood flow dose-dependently. Diabetic rats at 12 weeks, but not at 8 weeks, after the induction of diabetes showed a significant decrease in arachidonic acid response. However, there were no differences in papaverine response between diabetic and control rats. Pretreatment with ONO-3708, a selective thromboxane A2 antagonist, reversed the attenuated response to arachidonic acid found in diabetic rats. An increased response to thromboxane A2, which decreased inner ear blood flow, was also found in 12-week diabetic rats. In electrocochleograms, the latency in 12-week diabetic rats was significantly delayed compared with that in control rats, and this prolonged latency improved with insulin treatment. These results suggest that the responsiveness of inner ear blood flow to prostaglandins may be altered in individuals with diabetes mellitus. PMID- 1902645 TI - [Isolated tricuspid endocarditis. Apropos of a case caused by Streptococcus D bovis and faecalis occurring after coloscopy]. AB - A 59-year-old chronic alcoholic male, with no cardiac past history, was hospitalised with septicemia 5 months after the endoscopic removal of 2 benign intestinal polyps. The diagnosis of tricuspid endocarditis was possible only 2 months later on the basis of echocardiography requested because of the onset of a tricuspid systolic murmur. Blood cultures revealed the presence in succession of streptococcus D fecalis then bovis. Antibiotics, changed several times because of the onset of complications (allergy, agranulocytosis), failed to deal with the problem of infection as shown by the development of several septic pulmonary emboli which finally resulted in total tricuspidectomy with neither immediate nor secondary valve replacement. The authors use this clinical case to review the characteristics of tricuspid endocarditis, the incidence of which is on the increase in certain etiological contexts (staphylococcal endocarditis in drug addicts or secondary to central vascular lines). They stress that the clinical picture is often confusing since the murmur of tricuspid incompetence is absent in 2/3 of cases. Echocardiography must therefore be requested routinely in all septicemias, thus enabling earlier diagnosis and assessment of the risk of pulmonary embolism (risk if vegetation greater than 10 mm). The nature of the organism responsible may be suggestive of certain etiologies. Thus malignant disease of the colon should be sought if the bacterium is a streptococcus D bovis. Apart from antibiotics, treatment must include effective anticoagulation to decrease the risk of embolic recurrence.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1902646 TI - Mureidomycin A, a new inhibitor of bacterial peptidoglycan synthesis. AB - Mureidomycin A (MRD), a novel peptidylnucleoside antibiotic with antipseudomonal activity, inhibited not only peptidoglycan synthesis but also lipid-intermediate formation from UDP-N-acetylmuramyl (MurNAc)-pentapeptide and UDP-N acetylglucosamine in an in vitro peptidoglycan-synthesizing system, using ether treated cells of Pseudomonas aeruginosa. Both types of inhibition by MRD disappeared when UDP-MurNAc-pentapeptide was preincubated with ether-treated cells. Moreover, MRD completely inhibited lipid-intermediate I (undecaprenyl-p-p MurNAc-pentapeptide) formation at a concentration below the MIC. From these results, it was concluded that the real target of MRD's action was translocase, which catalyzes lipid-intermediate I formation from UDP-MurNAc-pentapeptide and a lipid carrier. PMID- 1902647 TI - Chromosomally mediated beta-lactamase production and gentamicin resistance in Enterococcus faecalis. AB - We have analyzed four distinct strains of multiply resistant, beta-lactamase producing enterococci isolated during an outbreak of colonization with these strains on an infant-toddler surgical ward at The Children's Hospital in Boston, Mass. All four strains were resistant to erythromycin, penicillin, and tetracycline and to high levels of gentamicin and streptomycin. One strain was also resistant to chloramphenicol. Plasmid profiles revealed four different plasmid patterns, with the number of identified plasmids ranging from zero to three. The gene coding for beta-lactamase production could be transferred at low frequency (less than 10(-8)) to an enterococcal recipient from one strain in conjunction with all of the other resistance determinants. Probes derived from the staphylococcal beta-lactamase gene and gentamicin resistance gene failed to hybridize with any of the detectable plasmids, but both genes were present on restriction fragments of genomic DNA in all strains. Our results indicate that the beta-lactamase genes and gentamicin resistance genes in these strains are integrated into the bacterial chromosome. The cotransmissibility of the resistance determinants raises the possibility of their incorporation into a multiresistance transposable genetic element. PMID- 1902648 TI - Damage to the cytoplasmic membrane and cell death caused by dodine (dodecylguanidine monoacetate) in Pseudomonas syringae ATCC 12271. AB - Treatment of Pseudomonas syringae cells with low concentrations of the fungicide dodecylguanidine monoacetate (dodine) resulted in cell death and leakage of K+, UV-absorbing materials, and ribose-containing molecules. The results suggest that dodine causes gross and extensive damage to the cytoplasmic membrane, which is probably implicated in the death of cells. PMID- 1902649 TI - Biochemical properties and purification of metallo-beta-lactamase from Bacteroides fragilis. AB - The beta-lactamase from Bacteroides fragilis GAI-30144 hydrolyzed imipenem, oxyiminocephalosporins, cephamycins, and penicillins. Enzyme activity was inhibited by EDTA. Zinc completely reversed inactivation of the enzyme by EDTA. The molecular mass of purified enzyme was estimated to be 33,000 daltons. PMID- 1902650 TI - Staff training: a key factor in reducing intravascular catheter sepsis. AB - A children's hospital nutritional care team prospectively monitored the frequency of sepsis in central venous catheters used for administering parenteral nutrition. During an initial study period of 12 months, 26/58 (45%) of catheters were removed because of proved sepsis. The possible causes of this alarmingly high rate were examined, with catheter care techniques on the wards coming under particular scrutiny. As a result protocols were modified and an intensive staff training programme implemented throughout the hospital, led by the nutritional care sister. Subsequently, the catheter sepsis rate was significantly reduced with only 9/107 (8%) of consecutive catheters becoming infected. These findings emphasise the key role that education of staff plays in controlling central venous catheter sepsis and the importance and cost effectiveness of special nursing staff in implementing such measures. PMID- 1902651 TI - HIV infection and haemophilia. PMID- 1902652 TI - Oxygenation of cardioplegic solutions: a note of caution. AB - The merits of oxygenated crystalloid cardioplegic solutions have been well established in experimental animals. The positive effects of oxygenation of Plasmalyte B (Sabax Ltd) and St. Thomas Hospital solution (Plegisol) were achieved by gassing with 95% O2/5% CO2 and 100% O2, respectively. In view of the marked pH differences induced by these gas mixtures, we evaluated the effect of mode of oxygenation on myocardial recovery during reperfusion after hypothermic cardioplegic arrest. Oxygenation with 100% O2 of Plasmalyte B containing high K+ levels caused marked deterioration in myocardial recovery, whereas the mode of oxygenation did not affect recovery after arrest with St. Thomas Hospital solution. Because the major differences between these solutions reside in their respective K+, Mg2+, and HCO3- contents, the effects of variations in the levels of these ions were investigated. The results showed that oxygenation with 100% O2 was deleterious only in the presence of high K+ (29 mmol/L), low Mg2+ (3 mmol/L), and high NaHCO3 (28 mmol/L) levels. The marked decline in mechanical recovery during reperfusion was associated with significant changes in myocardial adenosine triphosphate and intracellular Ca2+ levels. Although an explanation for these findings is not readily available, it is suggested that complex ionic interactions and possibly oxygen free radical generation may lead to intracellular Ca2+ overload, depression in mitochondrial adenosine triphosphate generation, and, hence, deterioration in mechanical recovery. PMID- 1902653 TI - Production of endothelium-derived contracting factor is enhanced after coronary reperfusion. AB - To determine whether coronary reperfusion enhances the production of endothelium derived contracting factor, we investigated dogs subjected to global cardiac ischemia (45 minutes) followed by reperfusion (60 minutes). Segments of reperfused and control coronary arteries were suspended in organ chambers to measure isometric force. Perfusate hypoxia caused endothelium-dependent contraction in the control and reperfused arteries. However, reperfused arteries exhibited hypoxic contraction that was significantly greater than control segments. The hypoxic contractions in both the control and reperfused arteries could be inhibited by NG-monomethyl-L-arginine (L-NMMA), the blocker of endothelial cell synthesis of nitric oxide from L-arginine. The action of L-NMMA could be reversed by L-arginine but not D-arginine. Thus, after reperfusion, augmented production of endothelium-derived contracting factor occurs by an L arginine-dependent pathway. We hypothesize that nitric oxide produced by L arginine metabolism combines with superoxide anion to produce the peroxynitrite anion (ONOO-), which is metabolized to endothelium-derived contracting factor or induces its synthesis. Augmented production of endothelium-derived contracting factor would favor vasospasm after reperfusion. PMID- 1902654 TI - Infected intravenous port device causing tricuspid valve regurgitation. AB - Sepsis and tricuspid valve regurgitation developed in a 29-year-old man with Crohn's disease after implantation of an intravenous port device for parenteral nutrition. A thrombus, caused by Staphylococcus epidermidis, had grown along the catheter and prolapsed through the valve without affecting it. Complete removal in an open heart procedure led to quick recovery. PMID- 1902655 TI - Evolution of therapy for pharyngoesophageal (Zenker's) diverticulum. PMID- 1902656 TI - [Combined etiological and pathogenetic therapy of urogenital Ureaplasma-Chlamydia gonococcal infection in men]. AB - One hundred and sixteen males with mixed Ureaplasma ++, chlamydial and gonorrheal urethritis were treated. 22 of them suffered from recent torpid urethritis and 94 were chronic patients including those with complications. The diagnosis was confirmed by the laboratory tests. The patients were subjected to complex treatment with immunostimulation (by the gonorrhea vaccine, methyluracil and pyrogenal), local therapy and the use of antibiotic combinations on day 8: gentamicin (0.84 g per treatment course) and doxycycline (2.1 g per treatment course). The treatment course was equal to 14 days. Favourable etiological and clinical results were observed in 114 patients. The recovery was confirmed by 3 fold verification. A high efficacy of the developed method studied clinically was stated. PMID- 1902657 TI - The use of albumin in clinical practice. AB - The use of albumin in the clinical setting continues to generate controversy. Periodic shortages and the high cost of albumin have compelled many hospitals to develop guidelines regarding albumin administration. Our purpose is to review the human studies involving albumin. Particular emphasis will be placed on comparative trials involving albumin and the less expensive crystalloid solutions. It is hoped that this review will assist the clinician in making judgements concerning the appropriate use of albumin. PMID- 1902658 TI - Prioritization of health care services. A progress report by the Oregon Health Services Commission. AB - The Oregon Health Services Commission is composed of a group of 11 consumers and health care professionals. It was appointed by the governor as required by the "Oregon Basic Health Services Act" to produce a prioritized list of health services ranked on the basis of their relative importance to populations served. Following actuarial analysis, the legislature will determine the extent to which the "list" of services can be funded to provide health care access for Medicaid recipients earning up to the 100th percentile of the federal poverty level. Prioritization will be based on a cost-benefit formula applied to each treatment/condition unit and assignment of each of these to a general category, which itself has been ranked on the basis of "public value." PMID- 1902659 TI - An update on the treatment of gonococcal ophthalmia. PMID- 1902660 TI - Lack of effectiveness of tissue plasminogen activator 20 or more days after vitrectomy. PMID- 1902661 TI - Retinal manifestations of neurofibromatosis. Diagnosis and management. AB - Five patients presented with vision-threatening retinal tumors and systemic signs of neurofibromatosis, including neurofibromatosis type 1 (four patients) and familial cafe-au-lait spots (one patient). These tumors included large retinal astrocytic hamartomas, multiple retinal capillary hemangiomas, and combined hamartomas of the retina and retinal pigment epithelium, which resulted in rubeotic glaucoma, vitreous hemorrhage, and retinal detachment. Surgical therapy included retinal cryopexy, xenon and argon photocoagulation, scleral buckling, and pars plana vitrectomy with excisional retinal biopsy. Retinal tumors may result in marked visual loss in patients with neurofibromatosis, and vitreoretinal surgery may restore useful vision in some of these patients. PMID- 1902662 TI - Intraocular penetration of topical tissue plasminogen activator. AB - Fifty-eight eyes of 31 anesthetized rabbits received one drop of proparacaine hydrochloride, 0.05%, and two drops of tissue plasminogen activator (tPA) separated by 5 minutes. Four eyes of two additional rabbits had epithelial defects created before drug delivery. Tissue plasminogen activator in multiple doses was given to eight eyes of four other rabbits. We used this dosing regimen to investigate the effect of topical tPA on anterior chamber fibrin clots in three rabbits. A two-site enzyme-linked immunosorbent assay test was used to measure tPA levels in the aqueous samples, obtained by paracentesis in each eye. Of 53 eyes treated with the original dosing regimen, 21 (40%) had detectable tPA aqueous levels. Blood and aqueous from eyes of untreated control rabbits, contralateral control eyes of treated rabbits, and eyes with epithelial defects had nondetectable tPA. Multiple tPA drop dosing resulted in 75% of aqueous samples with detectable tPA and a higher average tPA concentration than the original dosing regimen. Eyes treated with tPA showed a significantly faster resolution of anterior chamber fibrin clots than did control eyes. PMID- 1902663 TI - Retinal toxicity of human tissue plasminogen activator in vitrectomized rabbit eyes. AB - The retinal toxicity of human tissue plasminogen activator in normal rabbit eyes has recently been reported. We now report the retinal toxicity of tissue plasminogen activator in three groups of vitrectomized rabbit eyes. Group 1 underwent gas compression of the vitreous followed by tissue plasminogen activator injection in doses of 25, 50, and 100 micrograms (all doses were administered in 100 microL of fluid). Group 2 underwent lensectomy and vitrectomy followed by tissue plasminogen activator injection of 100 micrograms. Group 3 underwent lensectomy, vitrectomy, and complete fluid/gas exchange prior to injections of 12.5 and 25 micrograms of tissue plasminogen activator. Control eyes received 100 microL of balanced salt solution. In group 1, no retinal toxic reactions were observed after administration of 25 or 50 micrograms of tissue plasminogen activator, but all eyes receiving 100 micrograms demonstrated retinal damage on ophthalmoscopy, electroretinography, and light microscopy. In group 2, no retinal toxic reactions were seen after administration of 100 micrograms of tissue plasminogen activator. In group 3, two of 11 eyes receiving 25 micrograms of tissue plasminogen activator demonstrated toxic retinal changes by ophthalmoscopy, electroretinography, and light microscopy. These results suggest that gas compression of the vitreous does not significantly alter the toxic changes seen caused by tissue plasminogen activator. While lensectomy and vitrectomy appears to widen the therapeutic window for tissue plasminogen activator, the margin of safety is reduced with the addition of a large gas bubble. PMID- 1902664 TI - Thrombin induces a biphasic 1,2-diacylglycerol production in human platelets. AB - The 1,2-diacylglycerol (DAG) mass content was measured in thrombin-stimulated human platelets. Thrombin stimulates a biphasic accumulation of DAG, with an early phase reaching a peak at 10 s and a later phase reaching a peak at 2-3 min. The time course of first-phase DAG production corresponded well to that of Ins(1,4,5)P3 formation, which was rapid and transient. The second phase of DAG accumulation occurred after the level of Ins(1,4,5)P3 returned to nearly basal. Thrombin stimulated the decrease in PtdIns and phosphatidylcholine contents. The source of second-phase DAG was examined in platelets prelabelled with three radioactive fatty acids, i.e. arachidonic, palmitic and myristic. Thrombin stimulated the increase in radioactivity of DAG with decline of PtdIns in platelets labelled with [3H]arachidonic acid or [3H]palmitic acid, in which PtdIns was considerably labelled. In contrast, significant accumulation of [3H]DAG was not observed in [3H]myristic acid-labelled platelets, in which PtdIns was poorly labelled. In platelets prelabelled with [3H]inositol, an increase in InsP in response to thrombin was seen for more than 5 min. In contrast, upon stimulation, significant increases in [3H]phosphocholine and [3H]choline were not observed in [methyl-3H]choline-labelled platelets. Thrombin induced a small production of phosphatidylethanol, when ethanol was present during stimulation. However, the formation of DAG and phosphatidic acid was not significantly affected by ethanol. These results suggest that thrombin stimulates a biphasic accumulation of DAG, initially from PtdInsP2 and later from PtdIns in human platelets. PMID- 1902665 TI - Inhibition of high-affinity gamma-aminobutyric acid uptake in primary astrocyte cultures by phorbol esters and phospholipase C. AB - The effects of phorbol 12-myristate 13-acetate (PMA), a potent activator of protein kinase C (PKC), on high-affinity Na(+)-dependent gamma-aminobutyric acid (GABA) uptake were investigated in primary cultures of neurons and glial cells from rat brain cortex. Incubation of glial cells with PMA led to concentration- and time-dependent decreases in the GABA transport in glial cells. This effect could be completely suppressed by addition of the PKC inhibitor H7. The PMA effects could be mimicked by oleoylacetylglycerol, the diacylglycerol kinase inhibitor R59022 and exogenous phospholipase C. Treatment with PMA did not affect GABA transport in neuronal cells. PMID- 1902666 TI - Interaction domains of neurofilament light chain and brain spectrin. AB - We have previously demonstrated that brain spectrin binds to the low-molecular mass subunit of neurofilaments (NF-L) [Frappier, Regnouf & Pradel (1987) Eur. J. Biochem. 169, 651-657]. In the present study, we seek to locate their respective binding domains. In the first part we demonstrate that brain spectrin binds to a 20 kDa domain of NF-L. This domain is part of the rod domain of neurofilaments and plays a role in the polymerization process. However, the polymerization state does not seem to have any influence on the interaction. In the second part, we provide evidence that NF-L binds to the beta-subunit of not only brain spectrin but also human and avian erythrocyte spectrins. The microtubule-associated protein, MAP2, which has also been shown to bind to microfilaments and neurofilaments, binds to the same domain of NF-L as spectrin does. Finally, among the tryptic peptides of brain spectrin, we show that some peptides of low molecular mass (35, 25, 20 and 18 kDa) co-sediment with either NF-L or F-actin. PMID- 1902667 TI - A new photocatalytic material based on algal cells. AB - Metallic platinum was deposited at surfaces of intracellular photosynthetic membranes of whole cells of a cyanobacterium (blue-green alga). The deposited platinum particles acted as a catalyst for generation of hydrogen from photosynthetic decomposition of water in the absence of other exogenous electron transfer agents. This technique represents a means of placing metal catalysts in contact with intracellular structures of microorganisms. PMID- 1902669 TI - Human carbonyl and aldose reductases: new catalytic functions in tetrahydrobiopterin biosynthesis. AB - New catalytic functions of human carbonyl- and aldose reductase in tetrahydrobiopterin biosynthesis are proposed. 6-Pyruvoyl tetrahydropterin, an intermediate in the biosynthesis of tetrahydrobiopterin, was converted to 6 lactoyl tetrahydropterin and 1'-hydroxy-2'-oxopropyl tetrahydropterin by carbonyl reductase under anaerobic condition. 1'-Hydroxy-2'-oxopropyl tetrahydropterin was subsequently metabolized to tetrahydrobiopterin by aldose reductase. Based on these results alternative pathways for the synthesis of tetrahydrobiopterin in patients with genetic defects of sepiapterin reductase are suggested. PMID- 1902668 TI - Glycolipid receptor binding specificity of exoenzyme S from Pseudomonas aeruginosa. AB - By use of the tlc overlay procedure we have shown that exoenzyme S extracted from cultures of Pseudomonas aeruginosa specifically binds to the glycolipids asialoGM1, asialoGM2 and to a lesser extent lactosyl ceramide. More significantly, strong binding was also observed to the glycerolipid receptor we have detected for Helicobacter pylori (Lancet ii, 238-241.1989). Exoenzyme S can be extracted in a toxic and nontoxic form. Toxicity correlated with ability to bind the H. pylori receptor. This species was the only receptor detected in the most sensitive cell lines. The relative binding of exoenzyme S to the ganglio series glycolipids and the glycerolipid receptor was modified in a reciprocal manner in the presence of metal ions, suggesting that exoenzyme S has two interrelated receptor binding sites. PMID- 1902670 TI - Immunoreactivity and proliferative actions of beta 2 microglobulin on human bone derived cells in vitro. AB - Recent studies have demonstrated homology between bone-derived growth factor and beta 2 microglobulin. We have shown that beta 2 microglobulin has proliferative actions on human bone-derived cells in vitro and that these cells also show immunogenicity for beta 2 microglobulin. beta 2 microglobulin stimulated the incorporation of 3H-thymidine into DNA of human bone cells in a dose-dependent manner. In contrast to this stimulatory action, beta 2 microglobulin had no detectable activity with the same concentration on the production of osteocalcin, alkaline phosphatase activity or prostaglandin E2 synthesis. The possibility that the human bone-derived cells could also produce beta 2 microglobulin was examined. Under basal conditions these cells exhibit immunoreactivity for beta 2 microglobulin, the expression of which could be enhanced following treatment with interferon gamma in a dose-dependent manner. The co-localization of staining for beta 2 microglobulin and alkaline phosphatase, a marker of the osteoblast phenotype, indicate that human osteoblast-like cells represent a source of activity of this factor. The production of beta 2 microglobulin by human osteoblast-like cells and the subsequent action of this factor on cells within the bone microenvironment may indicate a role for beta 2 microglobulin as a local regulator of bone metabolism. PMID- 1902671 TI - Enantiospecific change in products for aldose reductase-mediated reaction of glyceraldehyde with bound NADP+. AB - Aldose reductase-mediated reaction of glyceraldehyde with enzyme-bound NADP+ gives different products depending on the enantiomer used. D-Glyceraldehyde reacts to form a chromophore (336 nm) similar to the covalent NADP-glycolaldehyde adduct characterized previously [Grimshaw et al. (1990) Biochemistry 29, 9936 9946]. L-Glyceraldehyde, however, reacts in a slow steady-state process to form an additional chromophore whose spectral properties (lambda max 290 nm, epsilon approximately 16,700 M-1cm-1) suggest that hydration of the nicotinamide 5,6 double bond has occurred. Several mechanisms are proposed to explain this unique stereoisomer-dependent change in reaction pathway. PMID- 1902672 TI - Identification in human genomic DNA of the sequence homologous but not identical to either the histo-blood group ABH genes or alpha 1----3 galactosyltransferase pseudogene. AB - Based on polymerase chain reaction (PCR) and sequencing of the cloned amplified fragments, we identified a homologous sequence to the histo-blood group ABH genes and alpha 1----3 galactosyltransferase pseudogene. The presence of this sequence in human genomic DNA was confirmed by Southern hybridization. PMID- 1902673 TI - Inhibition of lipoxygenase and prostaglandin endoperoxide synthase by anacardic acids. AB - C22:1 omega 5-anacardic acid was found to be a good inhibitor of both potato lipoxygenase and ovine prostaglandin endoperoxide synthase with approximate IC50's of 6 and 27 microM, respectively. Very similar inhibition was seen with the crude exudate, rich in omega 5-anacardic acids, from glandular trichomes of an arthropod-resistant strain of geranium, Pelargonium xhortorum. The saturated anacardic acid (C22:0 sat), abundant in the trichome exudate of susceptible strains, was nearly as inhibitory toward both prostaglandin endoperoxide synthase and lipoxygenase as the omega 5-unsaturated compound. However, the dimethyl derivative of C22:1 omega 5-anacardic acid was a poor inhibitor of prostaglandin endoperoxide synthase and caused only moderate (32%) inhibition of lipoxygenase even at 135 microM. The possible role of prostaglandin endoperoxide synthase and lipoxygenase inhibition in the enhanced pest resistance of geraniums which produce the omega 5-AnAs is discussed. PMID- 1902675 TI - [Orientation via modules. An example from intensive care]. PMID- 1902674 TI - Calcium oscillation induced by bradykinin in polyoma middle T antigen-transformed NIH3T3 fibroblasts: evidence for dependence on protein kinase C. AB - Bradykinin (BK) triggered long lasting intracellular free calcium ([Ca2+]i) oscillation in polyoma middle T-transformed cell line MT3 cells but not in the parental NIH3T3 cells. This periodic [Ca2+]i fluctuation was extracellular Ca(2+) dependent and blocked by pretreatments with Ca2+ channel blockers, SK&F 96365 or CdCl2, suggesting a crucial role of Ca2+ entry across the plasma membrane possibly through a receptor-operated Ca2+ channel. Brief pretreatment with phorbol myristate acetate (PMA) completely abolished the BK-induced [Ca2+]i oscillation, and a protein kinase C (PKC) inhibitor, H-7, reversed the effect of PMA, indicating involvement of PKC. On the other hand, in some cells, oscillatory changes in [Ca2+]i were seen without agonist stimulation. The spontaneous oscillation was also dependent on extracellular Ca2+, but neither treatment with PMA nor H-7 had any effect under the same conditions. PMID- 1902676 TI - [Learning from 10 Intermediate and 3ab. Exchange between a Dutch and a British pediatric ward]. PMID- 1902677 TI - [Fatigue in elderly patients: a nursing problem? 1]. PMID- 1902678 TI - [Primary health care in practice]. PMID- 1902679 TI - [Academic Hospital Utrecht. The administration is different]. PMID- 1902680 TI - [A psychiatric patient with a HIV infection, what is to be done?]. PMID- 1902681 TI - ['It remains a dish cloth disease'. Nursing of people with AIDS-related gastrointestinal disorders. 2]. PMID- 1902682 TI - [Quality of the COPD home care visit. Standards and criteria]. PMID- 1902683 TI - [Questions in rehabilitation remain. Response to Feil and De Klerk --TvZ no. 2, 1991]. PMID- 1902684 TI - [Het Groot Graffel, Warnsveld. The commotion is past]. PMID- 1902685 TI - [The word is mightiest. Writing policy memos by intermediate professional functionaries]. PMID- 1902686 TI - [Concept formation and reality in community health care]. PMID- 1902687 TI - [Project policy program CFO 1991-1994]. PMID- 1902688 TI - [Orthotopic liver transplantation in Groningen. Procedures, nursing care and psychosocial guidance]. PMID- 1902689 TI - [AIDS patients in the nursing home]. PMID- 1902690 TI - [Saint Maarten Hospital Venlo. So that the souffle won't collapse]. PMID- 1902691 TI - [Relationship with persons who attempt suicide and with their relatives. A course for intensive care nurses]. PMID- 1902692 TI - ['It remains a filling-in-the-gaps exercise'. Rob van der Peet about the revised 'Van der Peet series'. Interview by Toine de Graaf and Aart Eliens]. PMID- 1902693 TI - [Medica '91: efficiency and quality in the balance]. PMID- 1902694 TI - [The inspection. Government Inspectorate of Public Health]. PMID- 1902695 TI - [The inspection. 'We are very worried about nursing']. PMID- 1902697 TI - [Working with a learning record. Towards improved performance in professional education]. PMID- 1902696 TI - [A melancholy depression. The DSM-III-R diagnosis of Eline Vere]. PMID- 1902698 TI - [Shortages and power. Nurses, caregivers and the price of a box of strawberries]. PMID- 1902699 TI - The strength and periodicity of D. melanogaster circadian rhythms are differentially affected by alterations in period gene expression. AB - The per gene of D. melanogaster influences or participates in the generation of biological rhythms. Previous experiments have identified the head as the location from which per exerts its effect on circadian rhythms. To localize further this region and to examine the effects of altered levels and altered spatial expression patterns of the per gene on circadian rhythms of locomotor activity, we have characterized transformed lines containing per gene constructs missing substantial cis-acting regulatory information. The data suggest that wild-type levels of per gene expression are necessary in only a small fraction of the nervous system for near wild-type periods, whereas a larger fraction of per expressing cells in the brain contributes to the strength of the circadian rhythms. PMID- 1902700 TI - Improved spontaneous endothelialization by postfixation treatment of bovine pericardium. AB - The longstanding release of locally cytotoxic glutaraldehyde concentrations from fixed biological materials is one reason for the lack of spontaneous endothelialization in vivo and in vitro of biological grafts (and valves). Preliminary studies have shown that bovine pericardium postfixation-treated with aminoacids may be endothelialized in vitro. To test whether such treatment improves spontaneous endothelialization in vivo 8 cm long segments grafts (6 mm I.D.) were interposed into the carotid arteries of 10 sheep. Ten grafts were sewn from postfixation treated pericardium (PTP), 4 from standard glutaraldehyde fixed pericardium (GAP) and 6 polytetrafluoroethylane (PTFE) grafts were implanted to study the degree of spontaneous endothelialization. In two pregnant animals, all grafts occluded (2 PTP, 1 GAP, 1 PTFE). In the remaining animals 1 additional PTFE graft occluded and 2 PTFE and 1 GA grafts showed significant thrombotic obstruction. The patent grafts were harvested at 3 months and the surface covered with red thrombus was determined by planimetry. PTP grafts had significantly less (12.2% +/- 15%) thrombotic appositions than glutaraldehyde treated grafts (49% +/ 20%; P = 0.01) and PTFE grafts (40.5% +/- 13%; P = 0.01). In the central areas of the PTP grafts, endothelial cells spread directly on the collagenous matrix and produced a basal lamina. In GAP, endothelial cells spread on amorphous material or macrophages and in PTFE grafts, only a neointima composed of myofibroblasts was endothelialized. Neutralization of glutaraldehyde concentrations by postfixation with aminoacids improves spontaneous endothelialization in vivo in biological materials. PMID- 1902701 TI - Glutaraldehyde. PMID- 1902703 TI - Focusing AIDS research on behaviours. PMID- 1902702 TI - Clinical quiz. Diabetic ketoacidosis with severe dehydration, cerebral edema, and acute hypokalemia. PMID- 1902704 TI - Nurse turned consumer. Interview by Norah Casey. PMID- 1902705 TI - Relief nursing in Africa. PMID- 1902706 TI - Project 2000. Follow the reader. PMID- 1902707 TI - The challenge of intravenous therapy. AB - The simple intravenous infusion, seen commonly in most general wards, presents a far greater challenge to nursing awareness and skill than perhaps seems evident. Royal College of Nursing Adviser in Nursing Practice Rosemary Wilkinson discusses the management of problems they pose, and stresses the need for nurses to ensure that their relevant knowledge base is kept up to date. PMID- 1902708 TI - Infertility: the emotional aspects. AB - It may be that many health care professionals lack insight into the emotional needs of the infertile. In this article, Cherie Cottle addresses the psychological responses to infertility, which bear striking resemblances to the expected sequelae of bereavement. The role of the nurse in encouraging and assisting couples to acknowledge and accept their infertility is described with an emphasis on the need for a more sympathetic approach to such clients. PMID- 1902709 TI - Open for business. PMID- 1902711 TI - Clinical education. Relating practical experiments to theory. AB - Integrating theory into practice is not without its difficulties. Often concepts derived from the physical and behavioural sciences appear to be unrelated to nursing practice and although noted laboriously by student nurses no active learning occurs. As nurse education changes not only in curriculum content and teaching methodology but in who will do the teaching and in what venue, then the importance of ensuring the relevance of theoretical concepts to nursing practice will increase. This paper illustrates how physiological theory can be integrated into nursing practice by the use of ward-based practical experiments. Currently four such experiments have been introduced and are being evaluated. There is scope for developing further experiments and it is contended that this approach will enhance learning. PMID- 1902710 TI - Psychiatric nursing. Guidelines for successful relocation. AB - The physical and psychological repercussions of relocating chronically mentally ill patients from institution to community can be grave unless adequate preparation is offered well in advance and continuing support given throughout. Nurses, too, are not immune to the effects of relocation and require similar preparation and support. Hazel Nelson and her colleagues offer guidelines on preparation for relocation which are based on an extensive literature search and which represent a planned and structured approach to the process. PMID- 1902712 TI - The cost of quality. PMID- 1902713 TI - All together and united. PMID- 1902714 TI - Power to the project? PMID- 1902715 TI - Project 2000. Who's it all for? PMID- 1902716 TI - Project 2000. Sad, bad attitudes. PMID- 1902717 TI - Poll tax. Non-payment. PMID- 1902718 TI - Breakdown recovery. PMID- 1902719 TI - Muriel Williams RIP. PMID- 1902720 TI - A 24 hour day. PMID- 1902721 TI - AIDS publicity 'fails' visual test. PMID- 1902722 TI - Tipped for the top. PMID- 1902724 TI - Elderly care ideas. PMID- 1902723 TI - Thatcherite pedigree. Interview by John Naish. PMID- 1902725 TI - New vistas in wound care. Interview by Charlotte Alderman. PMID- 1902726 TI - Accident and emergency. Introducing triage to a new department. AB - The re-siting of the Tameside General Hospital accident and emergency department in a new, custom-built facility acted as the impetus for the formal introduction of the triage system of care. Ron Gray outlines the process of introduction and stresses that while problems have been encountered, the indications are that the system has worked to the benefit of patients and nurses. PMID- 1902727 TI - Tuberous sclerosis and its management. PMID- 1902728 TI - 'Rough and ready'. PMID- 1902729 TI - Nursing in a multicultural world. AB - The concept of nursing care which meets the needs of patients/clients from many diverse cultures is a relatively new one for British nurses. Barbara Weller explores the definitions and philosophies which surround the concept of transcultural nursing and urges nurses to avoid the adoption of narrow, ethnocentric attitudes in favour of a more critical and balanced view of cultural differences. PMID- 1902730 TI - Attitudes to old people: a review. Part 1. AB - In the first of two articles, Hamish Thomson reviews the research of the past decade related to learner nurses' attitudes towards elderly people. The concept of attitude is considered and related to work done on learner nurses' attitudes in general in this country and the United States. PMID- 1902731 TI - Management training for nurses. AB - Pauline Werhun and her colleagues describe an innovative approach to nurse management training in their health authority. The course they devised, which lasts a total of 18 months, received such a positive response from senior and charge nurses that there is now a waiting list for entry. Evaluations from participants also suggested areas where the course might be improved. PMID- 1902732 TI - Euthanasia is not the answer. PMID- 1902733 TI - I'll quote that again. PMID- 1902734 TI - Burn out. Cooling down. PMID- 1902736 TI - Upward management. PMID- 1902735 TI - Boiling over. PMID- 1902737 TI - Exchanging expertise. PMID- 1902738 TI - Diabetes nursing. A special function. PMID- 1902739 TI - Documenting diabetic care. PMID- 1902741 TI - Life insurance. HIV guidelines attacked. PMID- 1902740 TI - Diabetes nursing. An alternative education. PMID- 1902742 TI - The effect of topical nitroglycerin on transcutaneous oxygen. AB - The use of topical nitroglycerin has been reported to aid the healing of chronic skin ulcers. In this study, the effect of 2% nitroglycerin ointment on transcutaneous oxygen pressure (TcPO2) was investigated in skin adjacent to the area of ointment application. Topical nitroglycerin caused a two-fivefold decrease in TcPO2 in skin next to or up to 9 cm away from the site of application of the ointment. PMID- 1902743 TI - Acute myeloid leukaemia in childhood: the costs and benefits of intensive treatment. AB - Response to treatment and resource implications were compared in two groups of children with acute myeloid leukaemia (AML) treated during consecutive periods. Event-free survival at 5 years improved from 12% (SE 3.4) during 1972-82 (group A) to 45% (SE 6.9) during 1983-87 (group B). The median time spent in hospital increased from 35 to 170 d. Allogeneic marrow transplantation was offered to all eligible children in group B. Eleven of the 53 children had a suitable donor and 10 proceeded to bone marrow transplantation (BMT). The relapse rate was lower after BMT than after chemotherapy, although not significantly so. We conclude that there has been a real improvement in prognosis for children with AML; that modern treatment requires intensive hospital resources and that these results should encourage further efforts to improve outlook and to explore treatments not involving radiation. PMID- 1902744 TI - Variable inactivation of human factor VIII from different sources by human factor VIII inhibitors. AB - The source of human factor VIIII (FVIII) had a marked effect on the inhibitory activity of a panel of eight human FVIII inhibitors. Use of conventional FVIII concentrates gave lower inhibitor titres whereas a monoclonal antibody purified FVIII concentrate gave titres similar to or greater than those with plasma. Addition of phospholipid (PL) protected highly purified FVIII against inhibition. The content of PL-bound FVIII in concentrates may account for the observed differences. PMID- 1902745 TI - Angioedema during therapy with recombinant tissue plasminogen activator. PMID- 1902746 TI - Endogenous immunoglobulin expression in mu transgenic mice. AB - Transgenic mice (M54) containing a functional mu heavy chain were examined to determine the effects of the transgene on rearrangement and expression of endogenous immunoglobulin genes. Two major novel findings are presented. (i) In transgenic mice, the expressed endogenous VH repertoire in LPS-generated B cell blasts and hybridomas is skewed toward expression of JH-proximal VH families (VH7183 and Q52). (ii) There is an increase in the frequency of B cells expressing lambda light chain genes in transgenic mice. Furthermore, in Abelson MuLV transformed pre-B cells, VH to DJH is inhibited more than the D to JH rearrangement. The results presented indicate that the transgene skews the expressed VH repertoire by inhibiting the VH to DJH rearrangement while permitting an expansion of B cells expressing limited VH and lambda light chain genes. PMID- 1902747 TI - Mycoplasma contamination greatly enhances the apparent transport and concentrative accumulation of formycin B by mammalian cell culture. AB - S49 mouse leukemia cells exhibit both equilibrative and Na(+)-dependent, concentrative formycin B transport. The latter represents only a minor nucleoside transport component and is detectable only when equilibrative nucleoside transport is inhibited by dipyridamole or another transport inhibitor. Thus in uncontaminated S49 cells formycin B accumulated only to slightly above the intracellular-extracellular equilibrium level. In contrast, in suspensions of S49 cells contaminated with mycoplasma, formycin B accumulated in the intracellular water space in unmodified form to 40-50-times the extracellular concentration in a dipyridamole-independent manner during 90 min of incubation at 37 degrees C. The mycoplasma active formycin B transport system was inhibited by all nucleosides tested, including thymidine and deoxycytidine, which are not substrates for the concentrative nucleoside transporter of S49 cells. Mycoplasma contamination was detected by the presence of cell-associated adenosine phosphorylase activity. PMID- 1902748 TI - pH-dependence of inhibition by H2DIDS of mouse erythroid band 3-mediated Cl- transport in Xenopus oocytes. The effect of oligonucleotide-directed replacement of Lys-558 by an Asn residue. AB - The rapid reversible inhibition of band 3-mediated inorganic anion transport by 4,4'-diisothiocyanodihydrostilbene-2,2'-disfulfonate (H2DIDS) turns slowly into irreversible inhibition. This is due to covalent bond formation of the two isothiocyanate groups of the inhibitor with two lysine residues on band 3, called Lys a and Lys b. In the red cell membrane, the pK value of Lys a is about 2.5 pK units lower than the pK value of Lys b. Hence the susceptibility of Lys a to irreversible modification by H2DIDS far exceeds the susceptibility to Lys b. In the present paper, we have expressed in Xenopus oocytes cRNA's derived from cDNA clones encoding wild-type mouse band 3 and mouse band 3 in which Lys a (Lys-558) had been replaced by an Asn residue by oligonucleotide-directed mutagenesis. In accord with previous findings, in the oocytes both wild-type and mutated band 3 mediate Cl- exchange. After determining the uninhibited exchange rate the oocytes were exposed for a fixed length of time to H2DIDS at a concentration (20 microM) which saturates all H2DIDS binding sites with reversibly bound H2DIDS (KI = 0.3 microM and 1.1 microM, respectively, for wild-type and mutant). Exposure was terminated by washing with a medium in which H2DIDS was replaced by bovine serum albumin to remove free and reversibly bound H2DIDS from the extracellular phase. Subsequent measurements of Cl- efflux yielded a measure for the irreversible inhibition that persisted. Since the transition from reversible to irreversible H2DIDS binding was found to follow first-order kinetics it was possible to calculate rate constants. From the pH dependence of the rate constants, pK values were calculated. These calculations could be made since in the wild-type, in which Lys a and Lys b are present, the exposure to H2DIDS could be confined to a pH range in which little if any covalent binding to Lys b takes place. The data could be represented by a single pK value of 8.3. In the mutant, Lys a is missing. Hence, covalent reaction can only take place with Lys b. Measurements over the appropriate pH range could be described by a single pK of 10.8. These values are 0.8-0.9 pK units higher than those previously obtained in experiments with band 3 in the red cell membrane (Kampmann et al. (1982) J. Membr. Biol. 70, 199-216).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1902749 TI - Cloning and analysis of the gene (rpoDA) for the principal sigma factor of Pseudomonas aeruginosa. AB - A gene (rpoDA) of Pseudomonas aeruginosa whose gene product has a homologous function and structure with the principal sigma factor of Escherichia coli was cloned and sequenced. The DNA region corresponding to one of the two hybridization signals found in P. aeruginosa DNA with a synthetic oligonucleotide probe (rpoD probe) was shown to be able to complement a temperature sensitive mutation of Escherichia coli rpoD gene. The amino acid sequence deduced from the nucleotide sequence of rpoDA showed an extensive homology with that of the principal sigma factor of E. coli throughout the entire region, which indicates that the two gene products have an essentially identical domain structure. A common basic structure observed among principal sigma factors of different eubacterial strains was proposed. RpoDA protein was identified in the extract of the cell carrying a plasmid clone with the rpoDA gene insert by Western blot analysis. PMID- 1902750 TI - Centre for behavioural research in cancer. AB - The Centre for Behavioural Research in Cancer (CBRC) is one of two research centres housed at the Anti-Cancer Council of Victoria, the other being an epidemiological research centre. The CBRC's main focus for research is in smoking behaviour. A feature of the Centre is its close organizational and professional links with Victoria's large publicly funded smoking prevention programme. This provides opportunities to conduct programme-related research, to influence the nature of tobacco reduction interventions and to evaluate outcomes. PMID- 1902751 TI - Cancer treatment: deciding what we can afford. PMID- 1902752 TI - Does early intervention reduce the number of elderly people with dementia admitted to institutions for long term care? AB - OBJECTIVE: To test whether early diagnosis and practical help reduce the number of elderly people with dementia admitted to institutions. DESIGN: Controlled trial of effect of help from a multidisciplinary team on admission rates of people with dementia. SETTING: Seven general practices in Cambridge. SUBJECTS: 2889 subjects aged 75 and over, of whom 159 were identified as having dementia with a two stage community survey. Eighty six subjects were referred for extra help if they or their supporters wished. The other 73 subjects had access to the usual services and served as controls. INTERVENTION: Subjects and families in the action group were offered a wide range of help, including financial benefits, physical aids, home helps, respite admissions, practical advice, and psychiatric assessments. MAIN OUTCOME MEASURE: Permanent admission to long term care within two years after diagnosis. RESULTS: Early intervention did not affect admission rates in subjects who lived with supporters. By contrast, nine of the 14 (64%) subjects with moderate or severe dementia living alone were admitted in the action group in the study's second year compared with only one of 13 (8%) controls (p = 0.004). CONCLUSIONS: Some people with moderate or severe dementia who lived alone and were at serious risk may have been identified earlier by the resource team. Without the team these people would not have become known to the responsible authorities until families, neighbours, and wardens became unable to cope. The study was conducted during the team's formative period, however, and greater experience might have allowed some subjects to remain at home for longer. PMID- 1902753 TI - Audit of ankle injuries in an accident and emergency department. AB - OBJECTIVE: To determine whether the treatment of ankle injuries in an accident and emergency department could be improved by an audit of existing treatment and the creation and use of a protocol. DESIGN: The study consisted of three parts: a review of the current treatment and published reports on treatment, the formation of a protocol, and a study of treatment after introducing the protocol. SETTING: Accident and emergency department of a district general hospital. PATIENTS: 550 patients attending the department with ankle injuries over four months. RESULTS: The review of treatment showed that patients with fractures were detected and treated adequately, but most had radiography. Patients with ligamentous injuries may have been undertreated. After introducing the protocol the number of patients undergoing radiography was reduced from 205 (80%) to 186 (70%) (0.0027 less than p less than 0.01). In 87% of the notes reviewed the protocol had been completed. Sixty six patients with ligamentous injuries were reviewed in the department or soft tissue clinic compared with 20 before the protocol was introduced. There was a 53% reduction in inappropriate referrals to the fracture clinic (13 before v nine after). CONCLUSIONS: Using a protocol can, at little expense, improve the treatment of ankle injuries and reduce the cost of radiology in an accident and emergency department. IMPLICATION: Treatment of other conditions may be improved by introducing a protocol. PMID- 1902754 TI - Advances in treatment planning dosimetry for a high energy neutron beam. AB - Before starting the clinical programme, a series of physical measurements were made using the Clatterbridge high energy neutron facility. These consisted of measurements made under standard conditions, e.g. with square fields, full scatter conditions and perpendicular beam incidence. Further measurements have now been performed to include various clinically relevant non-standard conditions. These included the effects of field shape, backscatter, oblique incidence, bolus and beam blocking on dose distributions. PMID- 1902755 TI - Fact and fiction--results of the cardiac arrhythmia suppression trial. PMID- 1902756 TI - Enteral migration of a Foley catheter after jejunostomy. PMID- 1902757 TI - Increase of auto anti-phosphatidylinositol antibodies in plasma of female rats during the appearance of DMBA-induced malignant mammary tumors. AB - Using a lipid-adapted ELISA, antiphosphatidylinositol (PtdIns) antibodies (Ab) have been found in sera of cancer patients. With the same procedure, we have checked their possible raising in plasma of female rats during the appearance of 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumors. Twenty days after DMBA administration, the mean anti-PtdIns Ab level was already higher than that of control rats (oil). Immunochemical analysis of the anti-PtdIns Ab site showed a rather high Ab avidity (8 x 10(-9) M, at half-displacement) and high specificity for glyceryl phosphate inositol residues. Other phospholipids (PL) were not recognized by the anti-PtdIns Ab induced by malignant cell transformation. PMID- 1902758 TI - Influence of N-(o-methoxyphenyl)-maleimide on 5-fluorouracil cytotoxicity in Ehrlich (ascites) carcinoma. AB - N-(o-methoxyphenyl)-maleimide (I), an intermediate obtained during the synthesis of pyrrolidinedione-N-mustards, did not exhibit antitumor activity against Ehrlich (ascites) carcinoma. The effect of co-administration of (I), with established anticancer drugs was studied against P388 leukemia, S180 (ascites) and Ehrlich (ascites) carcinoma. A significant potentiation in the activity of 5 Fluorouracil (5-FU) against Ehrlich (ascites) carcinoma by (I) was observed. The possible mechanisms responsible for potentiation of the activity of 5-FU are presented. PMID- 1902759 TI - Ticlopidine: new option for stroke prevention. PMID- 1902760 TI - Long-term treatment of psoriasis with cyclosporin A--side-effects, minimal effective dose and cyclosporin blood levels. AB - Fourteen patients with psoriasis received long-term treatment with cyclosporin (CsA). Among patients there was great variability in the minimal effective CsA dose. In most patients long-term treatment was limited due to dose reductions made necessary because of side-effects. The therapeutic window for CsA seems small. CsA blood levels associated with side-effects and with the minimal effective dose are in the same range and correlation between CsA blood levels and effectiveness in psoriasis is weak. Therefore, in CsA therapy for psoriasis, without concomitant medication which may influence CsA blood levels, the measurement of CsA blood levels is not necessarily helpful in optimizing therapy or preventing side-effects. PMID- 1902761 TI - Killing of Mycobacterium tuberculosis within human monocytes: activation by cytokines and calcitriol. AB - Human monocytes were isolated and their ability to harbour growth of virulent tubercle bacilli was assessed, in the presence or absence of various immunomodulators. Calcitriol (1,25(OH2), vitamin D3) alone, at doses of 10(-7) 10(-9) M endowed human monocytes with a significant ability to restrict intracellular growth of the tubercle bacilli. Crude immune lymphokines as well as recombinant interferon-gamma (IFN-gamma) endowed monocytes with no tuberculostatic activity. Similarly, other recombinant cytokines tested, notably colony-stimulating factor-1 (CSF-1), interleukin-1 (IL-1), interleukin-3 (IL-3) and interleukin-6 (IL-6) all failed to stimulate anti-tuberculous properties, and even increased growth of the tubercle bacilli in monocytes, in the case of CSF-1. Conversely, incubation of crude lymphokines in combination with calcitriol led to total stasis of the growth of M. tuberculosis. Experiments with recombinant cytokines and immunologically active vitamins showed that a combination of IFN gamma tumour necrosis factor-alpha and calcitriol induced a significant amount of intramonocyte killing of M. tuberculosis. Addition of this cocktail of factors to already infected monocytes led to substantial killing of tubercle bacilli. These sets of experiments establish clearly that combinations of recombinant cytokines and vitamins may induce substantial intramonocyte killing of M. tuberculosis. The mechanism involved in this killing activity was not clarified. PMID- 1902762 TI - CD8+ T cells are the major lymphocyte subpopulation involved in the protective immune response to Toxoplasma gondii in mice. AB - The ability of the major T cell subsets to adoptively transfer resistance to T. gondii infection was studied. Spleen cells harvested from mice with a 3-month T. gondii infection and cells from uninfected mice were enriched for T cells by nylon/wool purification. Adoptive transfer of these cells from both groups of donor mice led to a significant increase in the survival of syngeneic recipient mice infected intraperitoneally with 20 T. gondii cysts. Increased survival was mediated particularly by CD4-depleted but also, to a lesser extent, CD8-depleted subpopulations. These results were confirmed in T cell reconstituted athymic nude mice. Unfractionated T cells from chronically infected donors produced a significant inhibition of cyst formation in the brains of recipient mice measured 10 weeks after infection compared with control mice. The inhibition of cyst formation was ablated by pretreating T cells with anti-CD8 antibody and complement, but not anti-CD4 antibody and complement. Mice receiving cells from infected donors produced an early increase in their IgG1 and IgG2a antibody titres compared with mice given cells from uninfected animals. The depletion of either CD8+ or CD4+ immune cells appeared to have little effect on the antibody responses in recipient mice and there was no correlation between antibody levels and immunity. The results indicate that CD8+ T lymphocytes from convalescent T. gondii-infected BALB/c mice are the principal mediators of resistance to T. gondii, although CD4+ T cells appear to be involved during the acute phase of infection. PMID- 1902763 TI - Antiphospholipid antibodies and recurrent pregnancy loss. AB - Women with antiphospholipid antibodies have a significant risk of reproductive failure and adverse pregnancy outcomes. The incidence of recurrent abortion, fetal death, and intrauterine fetal growth retardation is significant. Women with a history of recurrent abortion and unexplained fetal death or a history of recurrent thrombotic episodes should be screened for the presence of antiphospholipid antibodies. The benefit of routine screening of pregnant women for the presence of these antibodies has not been established, and the yield from such screening studies has been found to be low. No treatment regimen has eliminated fetal loss and adverse pregnancy events completely in women with the antiphospholipid antibody syndrome. Even when treatment is instituted, maternal and fetal status must be monitored closely. Management of such patients has not been standardized, and various treatment regimens have been found to be efficacious. Multicenter randomized treatment trials are currently underway, and standardization of therapy in these patients may be achieved. PMID- 1902765 TI - Case report: renal lymphoma in a patient with Waldenstrom's macroglobulinaemia. AB - A case of lymphoma confined solely to the kidneys in a patient with Waldenstrom's macroglobulinaemia is described. Primary lymphomatous involvement of the kidney is very rare in this condition. Ultrasound showed enlarged kidneys partially encased by tumour masses. The radiological features are described and the literature reviewed. PMID- 1902764 TI - An updated comparison of drug dosing methods. Part I: Phenytoin. AB - The relationship between a dose of phenytoin and the resultant serum concentration is difficult to predict, and numerous dosing methods have been developed to quantify the dose required to achieve a specific concentration. This review brings up to date the earlier article in the Journal regarding predictive algorithms, various pharmacokinetics-based dosing techniques and Bayesian feedback methods for phenytoin dosing. The latest data support the original conclusions that dosing methods for phenytoin which incorporate an individualised approach or Bayesian principles tend to offer results superior to those from predictive algorithms. Bayesian methods have the additional advantage of using only 1 serum concentration, obtained under either steady-state or non-steady state conditions. There is still a need for future investigations that include prospective evaluations of predictive performance and cost-effectiveness data. PMID- 1902766 TI - Lipopolysaccharide-induced myocardial depression is not mediated by cyclooxygenase products. AB - BACKGROUND AND METHODS: We tested the hypothesis that a sublethal dose of lipopolysaccharide in vivo induces in vitro atrial depression in rats via release of cyclooxygenase products. Male Sprague-Dawley rats (mean weight 366 +/- 9 [SE] g) were injected iv at time 0 with Escherichia coli lipopolysaccharide (1 mg/kg, n = 22) or saline (2.5 mL, n = 11). Some animals injected with lipopolysaccharide were pretreated 30 mins before with ibuprofen (15 mg/kg, n = 7). At time 2 hrs, the hearts were harvested and the atria were immersed in tissue baths and attached to force displacement transducers. Blood was collected for measurement of thromboxane B2 (TxB2) by radioimmunoassay. Force of contraction and rate in response to four different preloads were measured. Afterward, the preload was changed to 1 g, and force of contraction and rate were evaluated in response to graded doses of isoproterenol. RESULTS: Force of contraction was significantly (p less than .05) lower at all preloads in animals given lipopolysaccharide. Pretreatment with ibuprofen did not prevent the depression in force of contraction but prevented the increase in TxB2 seen after lipopolysaccharide injection (p less than .05). The force of contraction and rate response to isoproterenol were similar across groups. CONCLUSIONS: These data suggest that cyclooxygenase products do not mediate lipopolysaccharide-induced cardiac dysfunction in the rat. PMID- 1902767 TI - Orthoclone OKT3: an overview of the monoclonal antibody and the nursing considerations it presents. PMID- 1902768 TI - [Laser therapy of membranous duodenal stenosis]. PMID- 1902769 TI - Fine-needle aspiration cytology in a case with features of chronic granulomatous disease. AB - Fine-needle aspiration cytology (FNAC) of enlarged cervical lymph nodes of a 9-yr old boy complaining of progressive weight loss showed a combination of a necrotizing granulomatous process and pigmented histiocytes. The diagnosis of chronic granulomatous disease (CGD) of childhood was proposed, and it was later confirmed by histology. Although the NBT test was negative, the patient responded well to prolonged bactericidal therapy with trimethoprim-sulfamethoxazole associated with parenteral nutrition, indicating a rare case of CGD with a negative Nitro-Blue Tetrazolium (NBT) test. The cytologic findings appear to be unique for this disease. PMID- 1902770 TI - OKT3 monoclonal antibody in cardiac transplant patients. AB - The nurse's role in caring for cardiac transplant patients involves attention to many details, including assessment of organ function, provision of care, and administration of immunosuppressive medications. OKT3 monoclonal antibody, an immunosuppressive agent under investigational use in the cardiac transplant population, requires special nursing considerations. PMID- 1902771 TI - [Materials for supervision and practice counseling (II). Development, testing and process related evaluation of a component model for supervision of hospital nursing personnel in the continuing education course "Foundations of psychological health promotion"]. PMID- 1902772 TI - [New nursing concepts in nursing education? Consideration on a teaching unit "ADL"]. PMID- 1902773 TI - [Teaching unit "vomiting"]. PMID- 1902774 TI - [Nursing aspects of artificial urinary diversion]. PMID- 1902775 TI - [Constipation--fecal incontinence. Diagnosis and surgical therapy]. PMID- 1902776 TI - [Nursing aspects of stoma care]. PMID- 1902777 TI - [From the ease of shitting to the highly sterile discharge of feces]. PMID- 1902778 TI - [Education to cleanliness for children]. PMID- 1902779 TI - [Behavior therapeutic treatment of enuresis and encopresis]. PMID- 1902780 TI - [Software for nursing. Results of a market study]. PMID- 1902781 TI - [Endoscopy of the joints]. PMID- 1902782 TI - [Prevention of infections in endoscopy. Position of the work group Endoscopy]. PMID- 1902783 TI - The 5'HS2 of the globin locus control region enhances transcription through the interaction of a multimeric complex binding at two functionally distinct NF-E2 binding sites. AB - The locus control region (LCR) of the human beta-globin locus consists of four hypersensitive regions (5'HS 1-4). One of these sites, 5'HS2, is active in both transient and stable transfection assays and transgenic mice. It has previously been shown that the jun/fos consensus binding sites in 5'HS2 are required for high levels of transcription. In this paper we show that it is the 5' of the two consensus sites that is required for this function with a contribution of the 3' site to the overall activity. The functional complex at both sites includes NF E2. Its role in HS2 is to provide 'enhancer' activity but is not required for position independent activation. High levels of enhancement are achieved by interaction of the NF-E2 sites with three downstream elements. One of these sites binds the known factor GATA-1, whereas the other two interact with two novel DNA binding factors (H-BP and J-BP). PMID- 1902785 TI - Different patterns of expression of beta-tubulin genes in Tetrahymena pyriformis during reciliation. AB - The ciliate Tetrahymena pyriformis contains one alpha-tubulin (alpha TT) and two beta-tubulin (beta TT1 and beta TT2) genes. The specific expression of these genes was investigated by Northern blot hybridization using oligonucleotide probes complementary to beta TT1 and beta TT2 genes and the coding region of the alpha-tubulin gene. The three genes are expressed producing 1.8-kb mRNAs but the level of beta TT1 mRNA is much higher than that of beta TT2 mRNA. During cilia regeneration, we found that the expression patterns of the alpha TT and beta TT1 genes are similar whereas that of the beta TT2 gene is different. The alpha TT and beta TT1 transcripts reached higher values between 60-120 min after the onset of reciliation than in exponentially growing cells, while beta TT2 transcripts were maintained at low levels during the whole period. The differences in the amounts of steady-state populations of the both beta-tubulin mRNAs do not correspond to the copy number per haploid genome. These differences could result from the fact that the promoter region of beta TT2 may contain highly structured sequences which would affect the binding of the respective trans-acting factor(s). The apparent transcription rate revealed a significant increase at 15 min of reciliation which could be responsible for the high levels of alpha TT and beta TT1 transcripts in the cytoplasm between 60-120 min of reciliation. This coordinated response to cilia regeneration of the alpha TT and beta TT1 tubulin genes is also a relevant aspect of our findings. Several conserved motifs found in their promoter regions led us to think that some of them may function as cis elements in the specific binding of nuclear protein factor(s). PMID- 1902786 TI - Post-translational processing of the amino terminus affects actin function. AB - We have studied the importance of N-terminal processing for normal actin function using the Drosophila Act88F actin gene transcribed and translated in vitro. Despite having different charges as determined by two-dimensional (2D) gel electrophoresis, Act88F expressed in vivo and in vitro in rabbit reticulocyte lysate bind to DNase I with equal affinity and are able to copolymerise with bulk rabbit actin equally well. Using peptide mapping and thin-layer electrophoresis we have shown that bestatin [( 3-amino-2-hydroxy-4-phenyl-butanoyl]-L-leucine), an inhibitor of aminopeptidases, can inhibit actin N-terminal processing in rabbit reticulocyte lysate. Although processed and unprocessed actins translated in vitro are able to bind to DNase I equally well, unprocessed actins are less able to copolymerise with bulk actins. This effect is more pronounced when bulk rabbit actin is used but is still seen with bulk Lethocerus actin. Also, the unprocessed actins reduce the polymerisation of the processed actin translated in vitro with the bulk rabbit actin. This suggests that individual actins do interact, even in non-polymerising conditions. The reduced ability of unprocessed actin to polymerise shows that correct post-translational modification of the N terminus is required for normal actin function. PMID- 1902784 TI - The bx region enhancer, a distant cis-control element of the Drosophila Ubx gene and its regulation by hunchback and other segmentation genes. AB - The Drosophila homeotic gene Ultrabithorax (Ubx) is regulated by complex mechanisms that specify the spatial domain, the timing and the activity of the gene in individual tissues and in individual cells. In early embryonic development, Ubx expression is controlled by segmentation genes turned on earlier in the developmental hierarchy. Correct Ubx expression depends on multiple regulatory sequences located outside the basal promoter. Here we report that a 500 bp DNA fragment from the bx region of the Ubx unit, approximately 30 kb away from the promoter, contains one of the distant regulatory elements (bx region enhancer, BRE). During early embryogenesis, this enhancer element activates the Ubx promoter in parasegments (PS) 6, 8, 10, and 12 and represses it in the anterior half of the embryo. The repressor of the anterior Ubx expression is the gap gene hunchback (hb). We show that the hb protein binds to the BRE element and that such binding is essential for hb repression in vivo, hb protein also binds to DNA fragments from abx and bxd, two other regulatory regions of the Ubx gene. We conclude that hb represses Ubx expression directly by binding to BRE and probably other Ubx regulatory elements. In addition, the BRE pattern requires input from other segmentation genes, among them tailless and fushi tarazu but not Kruppel and knirps. PMID- 1902787 TI - Effects of cholecystokinin, cholecystokinin JMV-180 and GTP analogs on enzyme secretion from permeabilized acini and chloride conductance in isolated zymogen granules of the rat pancreas. AB - Previous studies have shown that hormonal activation of the Cl- conductance in pancreatic zymogen granules (ZG) is closely related to enzyme secretion from acinar cells. We have now examined the role of guanine nucleotides in stimulated and unstimulated protein secretion from isolated digitonin-permeabilized pancreatic acini and in the Cl- conductance of isolated ZG. Protein secretion from permeabilized isolated acini, measured at 0.1 mM Ca2+, increased with increasing cholecystokinin octapeptide (CCK-8) concentrations and decreased at high CCK-8 concentrations. The maximum secretion, approximately twice the control level, was reached at 1 nM CCK-8. The CCK analog, CCK JMV-180, which supposedly acts as an agonist on high-affinity CCK receptors and as an antagonist on low affinity CCK receptors, stimulated maximum enzyme secretion at a CCK JMV-180 concentration of 0.1 microM and no decrease in secretion was observed at higher CCK JMV-180 concentrations, 0.1 mM guanosine 5'-[gamma-thio]triphosphate (GTP [S]) also increased the protein release by approximately twice that of the control and shifted the CCK-8 concentration causing maximum stimulation from 1 nM to 0.01 nM. GTP[S] concentrations greater than 0.1 mM inhibited protein release evoked by an optimal concentration of 1 nM CCK-8, 0.1 mM GTP[S] had no pronounced effect on the protein secretion stimulated by low concentrations of CCK JMV-180, but inhibited protein secretion evoked by CCK JMV-180 concentrations greater than 0.1 microM. This indicates that guanosine-nucleotide-binding proteins [G protein(s)] coupling to CCK receptors also mediate both CCK-induced increases and CCK-induced decreases of enzyme secretion at low and high CCK concentrations, respectively. ZG were prepared on a Percoll gradient from CCK-8-stimulated or CCK JMV-180-stimulated and unstimulated acini. Their Cl- conductances were estimated in the absence of Ca2+ and in the presence of 1 mM EGTA from the rate of decrease in absorbance following addition of the K+ ionophore valinomycin as a measure of ZG osmotic lysis. The Cl- conductance in ZG from CCK-8-stimulated and CCK-JMV-180 stimulated acini was maximally activated at 1 pM and 10 nM respectively. At higher agonist concentrations, Cl- conductance was decreased. Direct addition of 10 microM GTP[S] to isolated ZG from unstimulated acini increased the rate of lysis by approximately 40% of the control value. This effect was approximately additive to that of CCK-8 or of CCK JMV-180 prestimulation.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1902788 TI - Catalytic properties of phenol carboxylase. In vitro study of CO2: 4 hydroxybenzoate isotope exchange reaction. AB - Phenol is metabolized in a denitrifying bacterium in the absence of molecular oxygen via para-carboxylation to 4-hydroxybenzoate (biological Kolbe-Schmitt synthesis). The enzyme system catalyzing the presumptive carboxylation of phenol, tentatively named 'phenol carboxylase', catalyzes an isotope exchange between 14CO2 and the carboxyl group of 4-hydroxybenzoate (specific activity 0.1 mumol 14CO2 incorporated into 4-hydroxybenzoate x min-1 x mg-1 cell protein) which is considered a partial reaction of the overall enzyme catalysis; 14C from [14C]phenol was not exchanged into 4-hydroxybenzoate ring positions to a significant extent. The 14CO2 isotope exchange reaction was studied in vitro. The reaction was dependent on the substrates CO2 and 4-hydroxybenzoate and required K+ and Mn2+. The actual substrate was CO2 rather than HCO3-. The apparent Km values were 1 mM dissolved CO2, 0.2 mM 4-hydroxybenzoate, 2 mM K+, and 0.1 mM Mn2+. The cationic cocatalysts could be substituted by ions of similar ionic radius: K+ could be replaced to some extent by Rb+, but not by Li+, Na+, Cs+, or NH4+; Mn2+ could be replaced to some extent by Fe2+ greater than Mg2+, Co2+, but not by Ni2+, Zn2+, Ca2+, or Cu2+. The exchange reaction was not strictly specific for 4-hydroxybenzoate, however it required a p-hydroxyl group; derivatives of 4 hydroxybenzoate with OH, CH3 or Cl substituents in m-position did react, whereas those with substitutions in the o-position were inactive or were inhibitory. The enzyme was induced when cells were grown on phenol, but not on 4-hydroxybenzoate. Comparison of SDS/PAGE protein patterns of cells grown on phenol or 4 hydroxybenzoate revealed several additional protein bands in phenol-grown cells. The possible role of similar enzymes in the anaerobic metabolism of phenolic compounds is discussed. PMID- 1902789 TI - The involvement of extracellular calcium in the formation of 5-lipoxygenase metabolites by human polymorphonuclear leukocytes. AB - We have addressed the question why in the presence of a Ca2+ ionophore human polymorphonuclear leukocytes generate leukotrienes in high yields, but in only low amounts after stimulation by receptor agonists like fMLF (fM, formylmethionine), leukotriene B4 or platelet-activating factor (PAF), although a significant release of intracellular calcium can be measured. Using ionomycin we can show that from the two enzymes involved, phospholipase A2 and 5-lipoxygenase, the first requires a threshold level of about 350-400 nM calcium whereas 5 lipoxygenase shows a linear dependence on calcium and saturates at this concentration. Our data indicate that the Ca2+ requirement of phospholipase A2 can only be met by an additional influx of extracellular calcium, whereas 5 lipoxygenase will operate already at levels provided by intracellular stores. Consequently, the complexing of extracellular calcium by EGTA stops phospholipase A2 activity immediately, whereas added arachidonate can be still adequately metabolized by intracellular Ca2+ release triggered by fMLF or PAF. Interestingly, PAF shows a stronger extracellular component in its Ca2+ transient than fMLF, and also generates more 5-lipoxygenase metabolites. However, a clear correlation between the amount of 5-lipoxygenase metabolites and the extracellular Ca2+ signal was lacking, since maximal activity was achieved before the bulk of the extracellular calcium was monitored. Ca2+ influx after PAF stimulation could be blocked after 2 min by EGTA, but a further increase in the formation of 5-lipoxygenase metabolites was observed. In contrast ionomycin elicited 5-lipoxygenase activity could be stopped at any time shortly after EGTA addition. PMID- 1902791 TI - Density-related expression of caldesmon and vinculin in cultured rabbit aortic smooth muscle cells. AB - Quantitative immunoblotting techniques were used to study the effects of seeding density on the expression of caldesmon and vinculin variants, which are sensitive markers of vascular smooth muscle cell (SMC) phenotypic modulation in culture. Rabbit aortic SMC were seeded at different densities: 13 x 10(4) cells/cm2 (high density), 3 x 10(4) cells/cm2 (medium density), and 0.2 x 10(4) cells/cm2 (low density) and cultured in the presence of 5% fetal calf serum. Irrespective of cell density and growth phase, caldesmon150 was gradually and irreversibly substituted by caldesmon77, but at high seeding density this substitution proceeded at a slower rate. The fraction of meta-vinculin (smooth muscle variant of vinculin) was reduced after seeding SMC in culture, but was reestablished when the cells reached confluency. Thus, high SMC seeding density is essential but not sufficient to keep vascular SMC cultured in the presence of serum in the contractile phenotype. PMID- 1902790 TI - Molecular cloning of the gene for plant proliferating-cell nuclear antigen and expression of this gene during the cell cycle in synchronized cultures of Catharanthus roseus cells. AB - A cDNA library was screened for plant proliferating-cell nuclear antigen (PCNA) from Catharanthus roseus (periwinkle). A lambda gt11 cDNA library was constructed using poly(A)-rich RNA isolated from the cells in the S phase. A cDNA clone for PCNA was isolated by using a rice genomic clone, pCJ-1, which contains PCNA related gene sequences. The cDNA contains an open reading frame of 804 nucleotides, encoding a protein of 268 amino acids with a molecular mass of 29,765 Da. When conservative substitutions were included, a high degree of similarity (about 85%) was observed between the predicted amino acid sequence of periwinkle PCNA and that of human PCNA. Expression of mRNA for periwinkle PCNA was undetectable or very weak in quiescent cells, such as phosphate-starved cells, auxin-starved cells and cells in the stationary phase. In the synchronous progression of the cell cycle induced by the addition of phosphate or auxin, the active accumulation of periwinkle PCNA mRNA was observed preferentially in the S phase. When an inhibitor of DNA synthesis, aphidicolin, was added to the cells at the G1 phase, an increase in the level of PCNA mRNA was observed. The partial inhibition of protein synthesis at the G1 phase by a protein inhibitor, anisomycin, caused the arrest of cells in the G1 phase. No increase of the level of periwinkle PCNA mRNA was observed in cells arrested at the G1 phase by the inhibition of protein synthesis. These results indicate that the induction of mRNA for periwinkle PCNA occurred independently of the initiation of DNA replication, but that synthesis of certain proteins at the G1 phase was required for the induction of periwinkle PCNA mRNA at the S phase. PMID- 1902792 TI - In vitro response of T cells from aplastic anemia patients to antilymphocyte globulin and phytohemagglutinin: colony-stimulating activity and lymphokine production. AB - The aim of the present study was to compare the response of bone marrow (BM) lymphocytes from patients with aplastic anemia (AA) or normal controls to increasing doses of antilymphocyte globulin (ALG) or phytohemagglutinin (PHA). For this purpose BM T-enriched cells from 11 AA patients and 9 normal individuals were incubated with ALG (0-1000 micrograms/ml) or PHA (0%-10%) for 1 day, and the supernatants were tested for suppression/enhancement of granulocyte-macrophage colony-forming unit (CFU-GM) growth and for release of granulocyte-macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma) assayed with the enzyme-amplified sensitivity immunoassay (EASI). The production of colony-stimulating activity (CSA) by T cells primed with ALG and tested in the absence of exogenous GM-CSF correlated with the dose of ALG in priming cultures up to 14% EG (100% EG = CFU-GM growth with 30 ng/ml of GM-CSF). The amount of GM-CSF in the supernatants paralleled their capacity to sustain CFU-GM growth (up to 3.5 ng/ml of GM-CSF). Production of CSA or GM-CSF from T cells primed with PHA was significantly lower. Supernatants of PHA-primed T cells, when added to normal BM cells in the presence of exogenous GM-CSF, produced a dose-dependent inhibition of CFU-GM growth (down to 13% +/- 10% EG). The same supernatants contained detectable amounts of IFN gamma and TNF-alpha (21 +/- 6.7 IU/ml and 4.6 +/- 2.9 ng/ml, respectively). IFN gamma production from severe AA (SAA) T cells in response to PHA was significantly superior to the IFN-gamma production from normal T cells (21 +/- 6.7 IU/ml vs 9.5 +/- 7.1 IU/ml, p = 0.02).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1902793 TI - Efficient introduction of a gene into hematopoietic cells in S-phase by electroporation. AB - Cells of the hematopoietic cell line K562 were synchronized by three different methods: single aphidicolin treatment, thymidine treatment followed by hydroxyurea exposure, and double hydroxyurea treatment. The synchronized cells were transfected via electroporation with plasmid pMoZtk, which contains the beta galactosidase gene, using a square wave pulse immediately after synchronization or at various time points during culture. Simultaneously, synchronized cells were fluorescence-activated cell sorter (FACS) analyzed to determine their stage in the cell cycle using double staining with bromodeoxyuridine (BrdU) and propidium iodide. Highly efficient introduction of pMoZtk was observed for the cell fraction, which predominantly consisted of the cells in S-phase. These results suggest that by increasing the proportion of cells in S-phase, the efficiency of gene transfer into hematopoietic cells such as hematopoietic stem cells can be improved. PMID- 1902795 TI - Trypanosoma cruzi: cytokine effects on macrophage trypanocidal activity. AB - Mouse macrophages infected with Trypanosoma cruzi in vitro may be activated to reduce parasite infection by interferon gamma (IFN-gamma). The addition of up to 10,000 units of IFN-gamma however, does not result in a 100% reduction of intracellular parasites. We, therefore, investigated the possibility that macrophages require an additional signal or signals to completely clear T. cruzi infection. Because the combination of IFN-gamma with lipopolysaccharide greatly enhanced macrophages ability to decrease the number of intracellular parasites, the interaction of IFN-gamma with tumor necrosis factor (TNF) was examined. TNF alone and the combination of TNF with IFN-gamma did not have a significant effect on reducing parasite numbers below that obtained with IFN-gamma alone. This was also true for lymphotoxin, a lymphokine similar to TNF in structure and function. The effect of IFN-gamma in combination with a cytokine-rich supernatant containing IL-2, IL-3, IL-4, IL-5, and IFN-gamma on macrophage clearance of the parasite was also examined. The cytokine-rich supernatant alone had no effect on reducing parasite infection of the macrophages; indeed, in some experiments the addition of the supernatant resulted in an increase in the level of parasite infection. However, 1000 units of IFN-gamma combined with the complex cytokine mixture caused a decrease in parasite infection of nearly 100% compared to that of control cultures treated with media alone. To determine which cytokine or cytokines in the supernatant were responsible for this synergistic activity, anti cytokine antibodies were added to the supernatant prior to its addition with IFN gamma to the cultures. Anti-IL-4 was the only antibody found to inhibit the synergism of IFN-gamma with the cytokine-rich supernatant. IL-4, however, did not significantly enhance the ability of IFN-gamma to induce macrophage clearance of the parasite, and IL-4 alone caused a slight increase in parasite infection in vitro. These results further define the role that cytokines play in T. cruzi infection of macrophages in vitro and suggest that the interaction of cytokine networks within this system is complex. PMID- 1902794 TI - Cholinergic neural transplants into hippocampus restore learning ability in monkeys with fornix transections. AB - Monkeys with bilateral transections of the fornix were severely but selectively impaired at learning visuospatial conditional tasks presented in a Wisconsin General Test Apparatus. Bilateral transplantation of cholinergic-rich embryonic basal forebrain tissue into the hippocampus led to complete recovery from this specific learning impairment across a range of task difficulties. Administration of the direct cholinergic agonist pilocarpine to ungrafted animals immediately before testing also reduced this impairment, suggesting that the graft-associated recovery was mediated by acetylcholine release. Transection of the fornix produced a marked loss of acetylcholinesterase (AChE) staining confined to hippocampus and entorhinal cortex relative to controls. In all transplanted animals densely AChE-staining cellular masses were seen bilaterally in temporal lobe structures, with fibre outgrowth into surrounding host tissue. PMID- 1902796 TI - Plasmodium falciparum: a comparison of synchronisation methods for in vitro cultures. PMID- 1902797 TI - Measles, killer of millions in developing countries: strategy for rapid elimination and continuing control. AB - Measles, which is still killing about two million children a year in poor countries, was mostly eliminated within two to three months after the conclusion of a special, national mass vaccination campaign in which all children of a selected age group received measles vaccine subcutaneously during a period of days to months, regardless of a history of previous vaccination or measles. This strategy was tested in the Dominican Republic in 1985, in Cuba in 1986-87, and in the State of Sao Paulo, Brazil May 11-June 10, 1987. Subsequent control was maintained by different procedures in the three states. A simple, rapid indirect immunofluorescent test for IgM measles antibody, used in Greater Sao Paulo, was more efficient in confirming concurrent infection with measles virus than the hemagglutination inhibition test for IgG antibody, and only one blood specimen taken during the course of the rash was needed to confirm the etiologic diagnosis in 97.5% of 240 cases confirmed by IgM. In Greater Sao Paulo and Cuba, it was found that over 90% of the small number of suspect measles cases reported during the first year after the mass campaign, were not caused by measles virus. The cost of disposable syringes and needles in the State of Sao Paulo, where 8,565,230 children were vaccinated in 10,527 centers in 30 days, was U.S. $2,057,753 or 63% of the total. Immunization by aerosol could have vaccinated this number of children more easily and effectively in one day if each of the vaccination centers had been supplied with one plastic foot or hand pressure pump and nebulizer at a cost of only about U.S. $300,000. PMID- 1902798 TI - Ribosomal DNA fingerprinting of Listeria monocytogenes using a digoxigenin labeled DNA probe. AB - A nonisotopic ribosomal DNA fingerprinting technique was developed for the characterization of Listeria monocytogenes. Plasmid pKK3535 (a pBR322-derived plasmid containing rrnB ribosomal RNA operon of Escherichia coli) was labeled with digoxigenin-11-dUTP by random priming and used to probe EcoRI fragments of L. monocytogenes chromosomal DNA on nylon filters. The method was successfully applied to the characterization of two sets of patient and food isolates of L. monocytogenes. PMID- 1902799 TI - Radiographic chest assessment of lung injury following hemithorax irradiation for pleural mesothelioma. AB - To characterize the nature, extent and time-course of radiation-induced lung injury, and to evaluate the usefulness of serial chest radiographs in this assessment, we studied 253 chest radiographs of 46 patients with pleural mesothelioma given hemithorax irradiation according to one of four different regimens: I 20 Gy; II 55 Gy; III hyperfractionation 70 Gy; IV hyperfractionation 35 Gy followed by local hypofractionation 36 Gy. Lung injury on the chest radiograph was graded from 0 (none) to V (maximal) based on the degree of loss of aerated lung tissue. Grade I changes were present 1-2 mths after radiotherapy in regimens II-IV. Grade V injury had developed in all but 3 out of 4 patients of the 20 Gy group by 6-12 months after irradiation. The extent and time-course of radiation-induced lung injury could be defined by serial chest radiographs alone. However, the documentation of tumour status and/or infections needed additional imaging or laboratory investigation, especially when grade IV-V lung injury was present. For research protocols evaluating radiation-induced lung injury serial chest X-rays are recommended at the following time-points: before treatment and 2, 6 and 12 mths after treatment, with additional computerized tomographic (CT) scans as required for differential diagnosis. PMID- 1902800 TI - Purification of two thermostable components of messenger ribonucleoprotein particles (mRNPs) from Xenopus laevis oocytes, belonging to a novel class of RNA binding proteins. AB - We have purified and partially sequenced two proteins from Xenopus laevis previtellogenic oocytes, belonging to messenger ribonucleoprotein particles (mRNPs). The purification procedure rests on the thermostability of these proteins, which remain soluble after heating the cell extracts at 80 degrees C. The thermostable proteins can be identified with two of the most abundant components (mRNP3 and mRNP4) of the mRNPs, described by Darnbrough and Ford (1981) [Eur. J. Biochem. 118, 415-424]. mRNP3 and mRNP4 are homologous to each other, but to no other protein of known sequence. The abundance and semi-periodic distribution of proline residues in mRNP3 and mRNP4 sequences suggest that these RNA-binding proteins adopt an unusual type of conformation. PMID- 1902801 TI - NADH:ubiquinone oxidoreductase from bovine heart mitochondria. Complementary DNA sequence of the import precursor of the 10 kDa subunit of the flavoprotein fragment. AB - The amino acid sequence of the 10 kDa subunit of the flavoprotein (FP) fragment of complex I from bovine heart mitochondria has been determined by protein sequence analysis, thereby completing the sequence of the FP fragment. The calculated molecular weight of the 10 kDa subunit agrees exactly with the value of 8438 determined by electrospray mass spectrometry, and further confirmation of the sequence has been obtained by sequencing cDNAs amplified from total bovine heart cDNA by the polymerase chain reaction, using mixed oligonucleotides based upon the protein sequence as primers and hybridization probes. The sequence of the 10 kDa subunit is not related to that of any known protein. Being devoid of cysteine residues, it has none of the characteristic features of known iron sulfur proteins and it is improbable that it is involved in liganding Fe-S centers in the FP fragment. PMID- 1902802 TI - Peri-operative jejunostomy-tube feeding in reconstructive spinal surgery. AB - Eight malnourished children with neuromuscular spinal deformity were treated with jejunostomy tubes for supplemental feeding to attain appropriate weight before reconstructive surgery. All patients had significant gastro-esophageal reflux and had failed to gain weight during an eight-month oral supplementation program. There were no complications associated with the placement or use of the jejunostomy feeding tubes and all patients gained weight in a safe and predictable fashion, had successful spinal fusion and have maintained satisfactory weight at follow-up. Jejunostomy feeding is a safe and effective method of correcting malnutrition in patients with spinal deformity which precludes gastrostomy and Nissen fundoplication. PMID- 1902803 TI - Hemimegalencephaly: diagnosis and treatment. AB - Three boys with hemimegalencephaly are reported. Two suffered neonatal convulsions and the third presented with seizures at seven months. In each case the EEG was grossly abnormal, with spike and wave activity. All three have significant developmental delay and demonstrate other manifestations of the condition: macrocephaly in two, contralateral hemiparesis in one and one boy has ipsilateral facial hemihypertrophy and linear naevus. Hemimegalencephaly can be recognised on cranial ultrasonography, and the seizures may respond to benzodiazepine therapy. PMID- 1902804 TI - Hemispherectomy for intractable seizures. PMID- 1902805 TI - Individual stripe regulatory elements in the Drosophila hairy promoter respond to maternal, gap, and pair-rule genes. AB - Striped expression of the pair-rule gene hairy (h) plays a central role in regulating segmentation in Drosophila. We have used h-lacZ reporter gene fusions to delineate h sequences that drive individual stripe expression. We show that 14 kb of 5'-flanking DNA directs expression of seven lacZ stripes in the blastoderm embryo. Within this region, we identify discrete sequences required for expression of individual stripes 1, 5, 6, and 7, and dispersed elements active in the stripe 2 domain. Only the stripe 1 element directs lacZ expression in an accurate h stripe; stripes 5, 6, and 7 are displaced by one to two cells relative to their h counterparts. These results indicate that regulatory sequences are dispersed within the h promoter. We have determined the sensitivity of the lacZ stripes to maternal, gap, and pair-rule gene mutations. Our results suggest that different but overlapping subsets of gap genes regulate each stripe and that activation and repression are both important in generating the stripe pattern. PMID- 1902806 TI - The involvement of alcohol dehydrogenase and aldehyde dehydrogenase in alcohol/aldehyde metabolism in Drosophila melanogaster. AB - In this study we have examined the roles of alcohol dehydrogenase, aldehyde oxidase, and aldehyde dehydrogenase in the adaptation of Drosophila melanogaster to alcohol environments. Fifteen strains were characterized for genetic variation at the above loci by protein electrophoresis. Levels of in vitro enzyme activity were also determined. The strains examined showed considerable variation in enzyme activity for all three gene-enzyme systems. Each enzyme was also characterized for coenzyme requirements, effect of inhibitors, subcellular location, and tissue specific expression. A subset of the strains was chosen to assess the physiological role of each gene-enzyme system in alcohol and aldehyde metabolism. These strains were characterized for both the ability to utilize alcohols and aldehydes as carbon sources as well as the capacity to detoxify such substrates. The results of the above analyses demonstrate the importance of both alcohol dehydrogenase and aldehyde dehydrogenase in the in vivo metabolism of alcohols and aldehydes. PMID- 1902807 TI - Effect of lactation on the decline of brush border lactase activity in neonatal pigs. AB - It has been shown that during the early phase of lactation porcine milk contains high concentrations of hormones and growth factors. The aim of the present investigation was to examine the hypothesis that the temporal coordination of intestinal maturation in piglets can be extrinsically regulated through changes in the composition of milk during the suckling period. Gut morphology and the ontogeny of brush border lactase activity were investigated in piglets reared on two suckling regimens designed to expose the animals to compositionally distinct milk. The first group of animals were cross-fostered onto postcolostrum sows and thereafter suckled normally for up to eight weeks. These normally suckled (N) animals consequently received both early and late lactation products. The second group of piglets were cross-fostered each week, for up to eight weeks, onto newly farrowed sows which were postcolostrum. As a result of this repeated cross fostering (CF) these animals received only early lactation products. Animals were sacrificed at one, three, five, seven, and eight weeks postpartum. Biochemically active lactase decreased significantly (p less than 0.001) in both groups over eight weeks, but the rate of loss of activity was greater in the CF animals than in the N pigs by approximately 50% at week 3 and 25% at week 8. Quantitative histochemical analysis of lactase activity corroborated the biochemical data. At three weeks maximal enzyme activity was observed approximately 400 microns from the villus/crypt junction. Histochemically detected lactase decreased throughout the suckling period, but the intensity of reaction product was consistently weaker over the entire villus surface in the CF animals. Immunocytochemically detectable lactase was identified at the same sites as the histochemical reaction products. In addition, immunofluorescence microscopy showed the presence of histochemically undetectable enzyme on the basolateral and brush border membranes of both villus and crypt cells. Villus/crypt ratios were significantly lower (p<0.001) in the CF animals than in the N pigs between weeks 3 and 5. The results of this study suggest that lactation products can accelerate the loss of brush border lactase activity. The observed decline in biochemically and histochemically detected lactase was considered to be a consequence of reduced enterocyte lifespan, decreased synthesis of enzyme protein, or altered post translational modification of enzyme protein, or a combination of there. PMID- 1902808 TI - Spontaneous release of interferon gamma by intestinal lamina propria lymphocytes in Crohn's disease. Kinetics of in vitro response to interferon gamma inducers. AB - The spontaneous induced release of interferon gamma (IFN gamma) by cultured intestinal lamina propria lymphocytes was investigated in patients with Crohn's disease. In contrast to normal lymphocytes, intestinal lymphocytes from these patients spontaneously released IFN gamma and seemed to contain IFN gamma in their cytoplasm. Autologous peripheral lymphocytes did not release IFN gamma. When stimulated with interferon inducers lamina propria lymphocytes from Crohn's disease tissue showed an increase in IFN gamma release 24 hours after induction with no appreciable further increase over the next two days of culture, while in control cells, either peripheral or intestinal, IFN gamma release progressively increased, peaking 72 hours after induction. These findings indicate that in Crohn's disease the intestinal lymphocytes are stimulated in vivo to produce IFN gamma and that the spontaneous IFN gamma production is compartmentalised to the gut lymphocytes. These data support the concept that locally released IFN gamma has a crucial role in cell interactions in the lamina propria and contribute to the locally occurring immune phenomena in Crohn's disease, including the increased epithelial expression of major histocompatibility complex class II antigens. PMID- 1902809 TI - Biotransformation enzymes in human intestine: critical low levels in the colon? AB - Biotransformation or drug-metabolising enzymes have an important function in the detoxication of ingested toxic, carcinogenic, or tumour promoting compounds. Enzyme activity and isoenzyme composition of three biotransformation systems: glutathione S-transferase, uridine diphosphate-glucuronosyltransferase, and cytochrome P-450 were studied in normal small and large intestinal mucosa from three kidney donors. The activity of most drug-metabolising enzymes decreases slightly from proximal to distal small intestine, whereas in the mucosa of the large intestine a sharp fall in activity was observed. The isoenzyme composition for each of the three biotransformation systems changed from the small to the large intestine. Class Alpha glutathione S-transferases were not expressed in the colon, in contrast to the small intestine where both Alpha and Pi class isoenzymes are present. In addition, with monoclonal antibodies fewer protein bands for UDP-glucuronosyltransferases and cytochrome P-450 were detected in the colon. In the small intestine both isoforms P-450(4) and P-450(5) were present, whereas in the colon only reduced amounts of cytochrome P-450(4) could be visualised. For UDP-glucuronosyltransferase, 53 and 54 kDa proteins could be detected in the small intestine, but in the colon there was only weak staining of the 54 kDa band. In the normal human colon enzymes are less active and there are fewer isoenzymes present in the mucosa than in the small intestine. This implies a lower level of the detoxifying potential in the colon, which might be important in regard to the high rates of carcinogenesis in the colon. PMID- 1902812 TI - [AIDS patients want to die at home. Home care: infusion therapy is necessary]. PMID- 1902811 TI - A technique for managing terminally ill ovarian carcinoma patients. AB - A patient with terminal ovarian carcinoma was admitted with malnutrition, abdominopelvic pain, and an inoperable complete small bowel obstruction after failing standard therapy and several experimental regimens for her disease. Despite this serious situation, she had an overall high performance status. Instead of administering intravenous narcotics, providing nasogastric suction, and giving other supportive care to make her apparently imminent death as comfortable as possible, her malnutrition was treated with total parenteral nutrition administered through an indwelling central venous catheter during the night hours only. The pain was successfully treated with an indwelling epidural catheter with the continuous infusion of morphine through a portable pump carried by a shoulder strap. The intestinal obstruction was relieved by a percutaneous endogastric tube which drained spontaneously into a leg bag. This regimen allowed the patient complete daytime mobility. She remained active, largely at home, with slowly progressing tumor until her death 9 months after the institution of this supportive care. PMID- 1902810 TI - Probiotics in human medicine. PMID- 1902813 TI - [Therapy of chronic non-A, non-B hepatitis with interferon]. AB - Alpha interferon, administered at a dose of 1 to 3 million units three times a week over a period of 24 weeks, leads to normalization of the transaminases in about 50% of patients with chronic hepatitis C. About 50% of the initial responders experience a recurrent increase in transaminases (relapse). Thus, about 20% to 25% of chronic hepatitis C patients show a lasting response to treatment with alpha interferon. A better understanding of HCV replication and the effect of interferon might possibly lead to improvements in treatment resulting in a higher response and lower relapse rates. Side effects of alpha interferon are generally mild and reversible on termination of treatment. At present, alpha interferon cannot be recommended for asymptomatic patients or those with slowly progressive liver disease. PMID- 1902814 TI - [Long-term antihypertensive treatment in diabetes mellitus. Results with the calcium antagonist felodipine]. AB - In 17 hypertensive, insulin-treated diabetics (eight type 1 diabetics, nine type 2 diabetics) the effectiveness of 10 mg/day felodipine was investigated over a period of one year. In both groups, felodipine brought about a lasting decrease in blood pressure (p less than 0.05). After four weeks' treatment, type 1 diabetics experienced a 143% increase in albumin excretion, and an 83% increase in fractional albuminuria, as compared with the initial values (p less than 0.05). In type 2 diabetics, in contrast, albumin excretion decreased by 25%, fractional albuminuria by 48% (p less than 0.05; p less than 0.01, as compared with type 1 diabetics). After 28 weeks of treatment, the fractionale albuminuria in the two groups had decreased by 27% (p less than 0.05 compared with the short term response) and 37%, respectively. No change in hormone or metabolic parameters was observed. PMID- 1902815 TI - Immunopathology of chronic viral hepatitis. AB - This paper reviews the main necro-inflammatory liver lesions observed in chronic viral hepatitis B and their apparent immunological mechanisms. Focal necrosis seems to represent the mechanism for clearance of virus replicating hepatocytes by cytotoxic T lymphocytes under HLA class I restriction and with hepatitis B virus nucleocapsid antigens as target antigen. Piecemeal necrosis involves CD8+ lymphocytes, possibly with hepatocellular membrane autoantigens as target antigen. Confluent lytic necrosis (bridging hepatic necrosis) presumably results from humoral immune mechanisms. Focal necrosis, piecemeal necrosis and confluent lytic necrosis determine the extent of necro-inflammatory activity in liver biopsy specimens, classified as chronic persistent hepatitis (low activity) or chronic active hepatitis (high activity). The extent of necro-inflammatory activity fluctuates during the natural course of chronic viral hepatitis B: from low activity during the viral replicative phase, through high activity in the viral elimination phase, into low activity again in the ensuing viral integration phase. The role of HLA antigens, intercellular adhesion molecules, cytokines and accessory antigen presenting cells is emphasized. PMID- 1902816 TI - Interferons in chronic viral hepatitis. AB - Interferons represent the rapid defence system against viral infections. This review describes the types of interferon and their effects on chronic viral hepatitis. The role of interferon therapy for hepatitis B has been intensively evaluated over the last few years. Response rates of approximately 30% can be achieved by a 4- to 6-month course of alpha interferon treatment in non immunosuppressed Caucasian patients. Assessment of interferon therapy for hepatitis C has had to rely on indirect markers of disease activity. Current data available indicate response rates in terms of aminotransferase activities of about 50% of patients treated. However, relapse after discontinuation of alpha interferon treatment is common. At present there is no valid treatment procedure for chronic hepatitis D infection. Only a minority of patients with chronic hepatitis D appears to benefit even transiently from alpha interferon. PMID- 1902817 TI - Clozapine's cost-benefits. PMID- 1902818 TI - Molecular characterization of medium-chain acyl-CoA dehydrogenase (MCAD) deficiency: identification of a lys329 to glu mutation in the MCAD gene, and expression of inactive mutant enzyme protein in E. coli. AB - A series of experiments has established the molecular defect in the medium-chain acyl-coenzyme A (CoA) dehydrogenase (MCAD) gene in a family with MCAD deficiency. Demonstration of intra-mitochondrial mature MCAD indistinguishable in size (42.5 kDa) from control MCAD, and of mRNA with the correct size of 2.4 kb, indicated a point-mutation in the coding region of the MCAD gene to be disease-causing. Consequently, cloning and DNA sequencing of polymerase chain reaction (PCR) amplified complementary DNA (cDNA) from messenger RNA of fibroblasts from the patient and family members were performed. All clones sequenced from the patient exhibited a single base substitution from adenine (A) to guanine (G) at position 985 in the MCAD cDNA as the only consistent base-variation compared with control cDNA. In contrast, the parents contained cDNA with the normal and the mutated sequence, revealing their obligate carrier status. Allelic homozygosity in the patient and heterozygosity for the mutation in the parents were established by a modified PCR reaction, introducing a cleavage site for the restriction endonuclease NcoI into amplified genomic DNA containing G985. The same assay consistently revealed A985 in genomic DNA from 26 control individuals. The A to G mutation was introduced into an E. coli expression vector producing mutant MCAD, which was demonstrated to be inactive, probably because of the inability to form active tetrameric MCAD. All the experiments are consistent with the contention that the G985 mutation, resulting in a lysine to glutamate shift at position 329 in the MCAD polypeptide chain, is the genetic cause of MCAD deficiency in this family. We found the same mutation in homozygous form in 11 out of 12 other patients with verified MCAD deficiency. PMID- 1902819 TI - A dissociated induction of MCF-producing and MAF-producing T cells specific for Listeria monocytogenes in the in vitro primary culture system. AB - Using an in vitro primary culture system which we had previously established, the induction phase of Listeria monocytogenes-specific effector cells was analysed with respect to their abilities to produce effector lymphokines, macrophage chemotactic factor (MCF) and macrophage-activating factor (MAF). Listeria specific effector cells generated after in vitro culture of normal spleen cells with viable L. monocytogenes for 5 days conveyed L3T4+, Lyt-2-, Thy-1+ surface antigens and produced MCF and MAF in response to the secondary stimulation with heat-killed L. monocytogenes. The cells required for the induction of Listeria specific effector cells, which produce effector lymphokines, MCF and MAF, were L3T4+, Lyt-2-, Thy-1+ cells. The kinetic analysis revealed that the ability of these effector cells to produce MCF was generated earlier than that to produce MAF. Furthermore, using passive transfer of cells, the effector cells producing only MCF, which were generated early in culture, conferred delayed-type hypersensitivity (DTH) alone, but MCF- and MAF-producing effector cells generated late in culture conferred sufficient levels of DTH and acquired cellular resistance (ACR). These results indicate a dissociated production of MCF and MAF by L. monocytogenes-specific T cells generated in the primary in vitro culture system. PMID- 1902820 TI - Differential induction of cytokine-specific mRNA in human PBL after in vitro culture with either IL2 or IL4. AB - The present study was designed to investigate whether human equivalents of murine T helper cell subsets can be demonstrated by propagation of peripheral blood lymphocytes (PBL) with either recombinant human (rh) interleukin (IL) 2 or rhIL4 in the presence of neutralising antibodies. Cells of both cultures, termed T-IL2 or T-IL4, respectively, were challenged on day 8 using a combination of phorbol 12-myristate-13-acetate (PMA) and the Ca2(+)-ionophore A23187 (Io). Total cellular RNA was isolated at different time points after PMA/Io-stimulation and the expression of 7 distinct cytokine genes was assessed by Northern analysis. Whereas maximal accumulation of mRNA species for IL2, GM-CSF, TNF alpha and TNF beta did not reveal major differences between cells of T-IL2 and T-IL4 cultures, substantial differences emerged for the induction of IFN gamma and IL3 messages. Accumulation of IFN gamma-mRNA consistently was 2- to 13-fold higher in T-IL2 than in T-IL4 cells, depending on the time point of RNA harvest. In contrast, IL3 specific mRNA levels induced in T-IL4 cells were 2-5 times greater than those in T-IL2. If PBL cultured with IL2 for 7-8 days were subsequently shifted to IL4 and further propagated until day 14, the mRNA induction pattern seen for IFN gamma and IL3 was similar to that obtained if cells had continuously been propagated with IL2. Collectively, these results indicate a selective outgrowth of distinct responder phenotypes by IL2 or IL4 rather than a direct modulation of cytokine expression by these factors. PMID- 1902821 TI - Concerted evolution in a segment of the first domain exon of polymorphic MHC class II beta loci. AB - Genetic exchange of sequence information between members of a gene family, generally denoted gene conversion, causes a phenomenon called "concerted evolution" meaning that non-allelic genes do not evolve independently. The possible significance of this phenomenon in the evolution of major histocompatibility complex (MHC) class II genes has been investigated in the present study. The results of a phylogenetic analysis of human, mouse, bovine, and chicken class II sequences were consistent with the occurrence of gene conversion between polymorphic class II beta genes (i.e. DPB, DQB, and DRB) but not between these genes and the monomorphic DOB gene or between class II alpha genes. Gene conversion between polymorphic beta genes appears to be restricted to a gene segment between approximately nucleotide positions 94-286 in the first domain exon. Due to this genetic exchange, there is a greater interlocus similarity both at the DNA and protein level in this region than in the rest of the sequence. The region encodes a functionally important part of the class II molecule including more than half of the beta-chain residues of the antigen binding site and the residues in the alpha helix assumed to form contact with the T-cell receptor. The observed similarity in the alpha-helical region of class II beta molecules may be functionally significant for the utilization of the T-cell repertoire for antigen recognition in the immune system. PMID- 1902822 TI - Testing for interlocus genetic exchange in the MHC: a reply to Andersson and co workers. PMID- 1902823 TI - Is there a high rate of mitotic recombination between the loci encoding immunoglobulin VH and CH regions in gonial cells? AB - Rabbit sera from approximately 6000 offspring of matings informative for recombination at the immunoglobulin (Ig) heavy chain locus were tested with allotype antisera by double diffusion in gel. Seven recombinants were found, R1K R7K, and in every case the recombinational event had taken place in the male parent. Two single males each fathered two recombinant offspring: R2K, R4K and R5K, R6K. Four further recombinants, reported from other laboratories as well as two new, as yet not fully documented recombinants in our laboratory, also occurred in the male parent. The recombinational events either separated the a locus which encodes the VH region of Ig, from the loci encoding its CH region or separated a-ms from the remaining linked loci d-e-f-g. The recombination frequency is 7/6142, approximately 0.1%. Our findings suggests that the recombinations took place in mitotic divisions during spermatogenesis. This work is the first evidence of gonial crossing-over in a mammal. PMID- 1902825 TI - Alterations in mitogen-induced calcium mobilization and intracellular free calcium produced by 7,12-dimethylbenz(a)anthracene in the Jurkat human T cell line. AB - The purpose of these studies was to assess the effects of 7,12 dimethylbenz(a)anthracene (DMBA), an immunosuppressive polycyclic aromatic hydrocarbon (PAH), on Ca+2 mobilization induced by phytohemagglutinin (PHA) in the Jurkat human T cell line. Intracellular levels of free cytosolic Ca+2 were examined by flow cytometry using Indo-1 loaded cells. At doses of 3-30 microM, DMBA was found to produce a dose and time-dependent inhibition of Ca+2 mobilization in Jurkat following in vitro exposure. The decrease in Ca+2 mobilization was correlated with an increase in baseline levels of cytoplasmic free Ca+2. Two non-immunosuppressive PAH, benzo(e)pyrene and anthracene, failed to inhibit PHA-induced Ca+2 mobilization or alter baseline levels of free Ca+2. These results suggest that DMBA may produce immunosuppression by inhibiting Ca+2 mobilization or by altering Ca+2 homeostasis in activated T cells. PMID- 1902824 TI - HLA class II restriction of autoantibody production in patients with systemic lupus erythematosus. PMID- 1902826 TI - A single column, rapid quality control procedure for 6-[18F]fluoro-L-dopa and 6 [18F]fluorodopamine PET imaging agents. AB - 6-[18F]Fluoro-L-dopa and 6-[18F]fluorodopamine are promising PET imaging agents for visualizing cerebral dopaminergic centers and cardiac sympathetic innervation and function. Administration to humans requires a means to determine the purity before injection. We describe such a method using HPLC with u.v. and radioactivity detection and a single high-speed C-18 column with gradient elution. The procedure can resolve within 10 min these fluorinated catechols, their isomers, and dihydroxyphenylalanine. The chemical and radiochemical purity, and specific activity, can be determined before injection. PMID- 1902827 TI - Nutritional support of the surgical oncology patient. AB - Malnutrition is a common manifestation of cancer patients and has a significant negative impact on treatment and survival. The metabolic aberrations associated with tumor growth are complex, and nutritional repletion cannot always be accomplished with nutritional support. Ultimate survival depends upon the primary lesion. Oral nutrition should be used whenever patients can eat and are able to take in sufficient calories. Preoperative total parenteral nutrition (TPN) in well-nourished patients appears to be unwarranted at this time, but the efficacy of preoperative TPN in malnourished surgical patients is established. Patients undergoing radiotherapy and chemotherapy can also benefit from nutritional support when the appropriate patient population is selected. In patients who have a potentially treatable disease, their malnourished state should not be a contraindication to therapy, and every effort should be made to nutritionally support such patients. PMID- 1902828 TI - Nutritional support of the medical oncology patient. AB - Our current ability to favorably influence the adverse consequences of malnutrition in adult patients with established cancer is quite limited. Nutrient provision alone has not been successful in this regard. In fact, the approach of managing cancer patients with weight loss by solely providing calories is almost entirely extrapolated from clinical situations in which the presence of cancer is not a confounding problem and, therefore, may well be seriously flawed. These conclusions may not apply to situations in which special considerations hold, such as childhood malignancies and bone marrow transplantation. Current clinical management strategies for the cancer patient with weight loss require appropriate attention to the potential influence of the selected intervention on more than one parameter. As illustrated in Figure 1, nutritional support, whether by nutrient provision, pharmacologic administration, or a combination approach, differentially influences several parameters including nutritional status, abnormal host metabolism, gastrointestinal symptoms, and/or tumor growth. Changes in these parameters will influence the true end points with clinical relevance, which are patient survival and quality of life. Increased survival of patients with metastatic cancer has been difficult to achieve, even using chemotherapeutic regimens targeted directly at cancer growth. Similarly, nutritional support for patients with advanced cancer has not demonstrated improvement in this refractory parameter. Therefore, at the present time, clinicians must judge whether a nutritional support modality will favorably or unfavorably influence patient quality of life. This end point is of emerging importance in studies of nutritional support in cancer populations. Potential interrelationships among parameters influenced by nutritional support and their effect on clinically relevant end points are conceptually outlined in Figure 1. It is likely that concurrent attention to both optimal provision of nutrients and reversal of abnormal metabolism will be required if successful nutritional support approaches are to be described. Currently emerging clinical results provide some optimism for the future, but they do not unequivocally support the present routine application of any one particular nutrition support strategy for the medical patient with cancer. PMID- 1902829 TI - Nutritional support and cancer cachexia. Evolving concepts of mechanisms and adjunctive therapies. AB - Despite the widespread employment of intravenous feeding in patients with cancer cachexia to improve outcome, conflicting data exist regarding the efficacy of such therapy in addressing metabolic alterations secondary to immobility, malnutrition, and disease-specific processes. Persistence of distinct abnormalities of body and tissue integrity and peripheral tissue plasma inter organ nitrogen flux imply the need for anabolic agents to enhance the therapeutic effects of parenteral nutrition. This article focuses upon potential anabolic agents such as chronic submaximal exercise, hormonal augmentation, pharmacologic intervention, and variations in substrate composition. Finally, the immunologic, metabolic, and endocrine consequences of bypassing the gastrointestinal tract are considered and related to the limited efficacy of current total parenteral nutrition regimens. PMID- 1902830 TI - Clinical trials of nutritional support in cancer. Parenteral and enteral therapy. AB - Cancer-related malnutrition is associated with poor prognosis. Although logic would dictate that nutritional support should improve malnutrition and thus outcome, when tested by controlled clinical trials, this has not borne out. With the exception of bone marrow transplantation, routine specialized nutritional support, particularly parenteral nutrition, has not demonstrated consistent therapeutic benefit with respect to any outcome measure and may be associated with harm to patients. The clinician must carefully select appropriate indications for specialized nutritional support in cancer patients. PMID- 1902831 TI - Levels of pesticide residues in Egyptian human milk samples and infant dietary intake. AB - Contamination of human milk with residues of organochlorine pesticides and polychlorinated biphenyls was studied in a series of investigations concerned with the monitoring of these chemicals in Egyptian food. The DDT complex was the most frequently found pesticide, followed by total hexachlorocyclohexane isomers. Heptachlor and its epoxide, dieldrin, hexachlorobenzene, and oxychlordane were also found but less frequently. Estimated dietary intakes (EDIs) of these contaminants by the breast-fed infants were compared to acceptable daily intakes (ADIs). EDIs of DDT complex, lindane (gamma-HCH), heptachlor + heptachlor epoxide, and oxychlordane were below ADIs. Dieldrin EDI exceeded the acceptable daily intake. PMID- 1902832 TI - Synthesis of lipoxins and other lipoxygenase products by macrophages from the rainbow trout, Oncorhynchus mykiss. AB - Rainbow trout macrophages maintained in short term culture when incubated with either calcium ionophore, A23187, or opsonized zymosan synthesize a range of lipoxygenase products including lipoxins and leukotrienes. These cells are unusual in that they generate more lipoxin than leukotriene following such challenge. The main lipoxin synthesized was lipoxin (LX) A4. This compound was identified by cochromatography with authentic standard during reversephase high performance liquid chromatography, by ultra violet spectral analysis, radiolabeling following incorporation of [14C]arachidonic acid substrate into macrophage phospholipids, and gas chromatography electron impact mass spectrometry of the methyl ester, trimethylsilyl ether derivative. Other 4-series lipoxins synthesized by trout macrophages were identified as 11-trans-LXA4, 7-cis 11-trans-LXA4, and 6(S)-LXA4. These cells also produced 5-series lipoxins tentatively identified as LXA5, 11-trans-LXA5 and possibly 6(S)-LXA5. No LXB4 or LXB5 was, however, detected. The dynamics of leukotriene and lipoxin release were also determined. Lipoxin generation was slower than leukotriene generation the latter reaching a maximum after 30 min of exposure to ionophore (5 microM, 18 degrees C) compared with 45 min for the former. PMID- 1902833 TI - Human factor VIIIa subunit structure. Reconstruction of factor VIIIa from the isolated A1/A3-C1-C2 dimer and A2 subunit. AB - Heterodimeric human factor VIII was proteolytically activated by catalytic levels of thrombin to yield the (labile) active cofactor factor VIIIa possessing an initial specific activity of approximately 80 units/microgram. Activation paralleled the generation of fragments A1 and A2 derived from the heavy chain and A3-C1-C2 derived from the light chain. Chromatography of factor VIIIa, on Mono-S buffered at pH 6.0 resulted in separation of the bulk of the A2 fragment from a fraction composed predominantly of A1/A3-C1-C2 dimer plus low levels of A2 fragment. Only the latter fraction contained clotting activity (approximately 20 units/microgram) which was stable and represented a less than 10% yield when compared with the peak activity of unfractionated factor VIIIa. Further depletion of A2 fragment from Mono-S-purified factor VIIIA, achieved using an immobilized monoclonal antibody to the A2 domain, yielded a relatively inactive A1/A3-C1-C2 dimer (less than 0.4 unit/microgram). Factor VIIIa (greater than 40 units/microgram) was reconstituted from the A1/A3-C1-C2 dimer plus the A2 fragment in a reaction that was Me(2+)-independent and inhibited by moderate ionic strength. Reassociation of A2 required the A1 subunit in that the A2 subunit associated weakly if at all to A3-C1-C2 in the absence of A1. These results indicated that human factor VIIIa is a trimer represented by the subunits A1/A2/A3-C1-C2 and that the A2 subunit is required for expression of factor VIIIa activity. PMID- 1902834 TI - A new type of serine-containing glycopeptidolipid from Mycobacterium xenopi. AB - An unknown immunogenic glycopeptidolipid, named GPL X-1, was isolated from Mycobacterium xenopi, which is a nontuberculous mycobacterium responsible for pulmonary and disseminated infectious diseases mainly occurring in immunocompromised patients. The glycopeptidolipid was purified until homogeneity, in the native form, by direct phase high performance liquid chromatography. A new route is proposed for the structural elucidation of its unusual lipopeptidic core. The presence of allothreonine (aThr), phenylalanine, and serine in the molecular ratio 1:1:2, respectively, was established by reverse phase high performance liquid chromatography analysis of the phenylthiocarbamyl amino acid derivatives. From the molecular mass (1828 Da) of the native glycopeptidolipid, determined by cesium ion liquid secondary ion mass spectrometry using the amphipathic triethylene glycol monobutyl ether matrix, it was deduced that the tetrapeptide was amidified by a dodecanoic acid. The complete structure, C12-Ser Ser-Phe-aThr-OCH3, of the lipopeptidic core was established by pyrolysis electron impact-mass spectrometry of the native glycopeptidolipid. To date, this is the first example of a mycobacterial glycopeptidolipid with a C12-tetrapeptidic core containing serine. A novel approach, based on two dimensional 1H,1H correlated spectroscopy analysis of the native and peracetylated GPL X-1, was developed, allowing the structural determination of the monosaccharidic residues with their alkali-labile groups "in situ" on the whole complex molecule. 2-O-Acyl-alpha-L Rhap, alpha-L-Rhap, 2,4-di-O-acyl-6-deoxy-alpha-L-Glcp, 2,3,4-tri-O-Me-alpha-L Rhap, and 3-O-Me-6-deoxy-alpha-L-Talp were identified, where Me, Rhap, and Talp are methyl, rhamnopyranosyl, and talopyranosyl, respectively. The latter two were localized at the carbohydrate non-reducing ends, and the C-3's of the remaining monosaccharide residues were found involved in the interglycosidic linkage. The alpha anomeric configurations were inferred from the JC-1,H-1 heteronuclear coupling constants, and the L absolute configurations for all the monosaccharide residues were established by gas chromatography analysis of the trimethylsilyl (+/-)-2-butyl glycosides. Finally, by pyrolysis electron impact mass spectrometry of peracetylated GPL X-1, the following tetrasaccharide appendage structure was proposed: 2,3,4-tri-O-Me-L-Rhap(alpha 1----3)-2-O-lauryl-L-Rhap(alpha 1----3)-L Rhap- (alpha 1----3)-2,4-di-O-(acetyl,lauryl)-6-deoxy-alpha-L-Glcp. Compared to the oligosaccharidic glycopeptidolipid structures, the particular features of the GPL X-1 tetrasaccharide structure arise from the presence of monosaccharide residues esterified by C12 fatty acids and from the absence of the basal disaccharide core, L-Rhap-(alpha 1----2)-6-deoxy-alpha-L-Talp.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1902835 TI - Oscillations in cytosolic free Ca2+, oxygen consumption, and insulin secretion in glucose-stimulated rat pancreatic islets. AB - Insulin secretion in the intact organism, and by the perfused pancreas and groups of isolated perifused islets, is pulsatile. We have proposed a metabolic model of glucose-induced insulin secretion in which oscillations in the ATP/ADP ratio drive alterations in metabolic and electrical events that lead to insulin release. A key prediction of our model is that metabolically driven Ca2+ oscillations will also occur. Using the fluorescent Ca2+ probe, fura 2, digital image analysis, and sensitive O2 electrodes, we investigated cytosolic free Ca2+ responses and O2 consumption in perifused rat islets that had been maintained in culture for 1-4 days. We found that elevated ambient glucose increased the average cytosolic free Ca2+ level, the ATP/ADP ratio, and oxygen consumption, as previously found in freshly isolated islets. Oscillatory patterns were obtained for Ca2+, O2 consumption, and insulin secretion in the presence of 10 and 20 mM glucose. Very low amplitude oscillations in cytosolic free Ca2+ were observed at 3 mM nonstimulatory glucose levels. Evaluation of the Ca2+ responses of a large series of individual islets, monitored by digital image analysis and perifused at both 3 and 10 mM glucose, indicated that the rise in glucose concentration caused more than a doubling of the average cytosolic free Ca2+ value and a 4-fold increase in the amplitude of the oscillations with little change in period. The pattern of Ca2+ change within the islets was consistent with recruitment of responding cells. The coexistence of oscillations with similar periods in insulin secretion, oxygen consumption, and cytosolic free Ca2+ is consistent with the model of metabolically driven pulsatile insulin secretion. PMID- 1902836 TI - Aging affects expression of 70-kDa heat shock proteins in Drosophila. AB - We examined the effect of cellular aging on adult mortality and hsp70 gene expression in Drosophila melanogaster under thermal stress. The results showed that flies exposed to 37 degrees C for various time intervals had reduced survival rate with age. The level of hsp70 mRNA increases in flies up to 23-28 days of age, but then declines as they get older. When flies are shifted to 25 degrees C after 30 min of heat stress, the time-dependent decrease in hsp70 mRNA levels occurs more rapidly in young flies than in old ones. The hsp70 mRNA present during this recovery period is translated into protein, and senescent flies continue to synthesize this protein for up to 5 h after heat shock. The prolonged expression of hsp70 RNA during recovery from heat shock was also observed in young flies fed canavanine, an arginine analogue. These data suggest that in old insects, the accumulation of conformationally altered proteins plays a role in the regulation of hsp70 RNA expression. These results are discussed in relation to the finding that old flies are more sensitive to thermal stress than young ones. PMID- 1902837 TI - Solid versus liquid lithium--a pharmacokinetic study. AB - The pharmacokinetics of solid lithium (Priadel) were compared with liquid lithium citrate in nine manic depressive patients. The results show that whilst the 12-h steady-state levels are similar, there are significant differences in the degree and rate of absorption between the two preparations. The clinical implications of this are discussed further. PMID- 1902838 TI - An overview of the use of anti-tuberculous drugs in Uganda and Hong Kong. AB - Anti-tuberculous (Anti-TB) chemotherapy in Uganda is outlined. Its pattern of use and the subsequent shortcomings have prompted the need for the present review. A collateral comparison to that of Hong Kong was run to emphasize the correlation of anti-TB chemotherapy with economic development and regional variation in the population of the two areas. Tuberculosis of the central nervous system (CNS) has a high fatality rate. In the search for a more comprehensive anti-TB dosage regimen, the difficulty in treating tuberculosis of the CNS has attracted special attention with emphasis on the fate of anti-TB drugs across the meninges. The choice of a method for drug analysis in routine therapeutic drug monitoring for a country is likewise determined by factors similar to those for the anti-TB regimen. Uganda needs an inexpensive, precise and selective method for TB treatment tailored to its financial and manpower resources. PMID- 1902839 TI - Gas chromatographic-mass spectrometric characterisation of some novel hydroxyeicosatetraenoic acids formed on incubation of arachidonic acid with microsomes from induced rat livers. AB - The biotransformation of arachidonic acid by rat liver microsomes from both control animals and animals pretreated with known inducers of cytochrome P-450 isoenzymes has been studied using a combination of reversed- and normal-phase high-performance liquid chromatography and combined gas chromatography-electron impact mass spectrometry. The metabolite profiles observed were found to be dependent upon the inducing agent. Five metabolites were identified, namely 16-, 17-, 18-, 19- and 20-hydroxylated arachidonic acids. Of these the 16- and 17 isomers have not been reported as products of arachidonic acid metabolism by any biological system and the 18-isomer has not been reported as a product of liver metabolism. PMID- 1902840 TI - On-line measurements of 13C enrichments in rat breath. Non-invasive method for in vivo study of drug enzymatic induction. AB - A differential kinetic study of 13CO2 enrichment of breath after the intake of specific 13C-labelled substrates and co-administration of a drug allows the drug's ability for enzyme induction to be evaluated in vivo. A method and a gas chromatograph-isotope ratio mass spectrometer device for on-line measurements of 13CO2 enrichment in the breath of small animals are described. This system allows on-line breath sample collection from a metabolic cage, purification by gas chromatography, determination of CO2 by thermal conductivity detection and measurement of 13CO2 enrichment by isotope ratio mass spectrometry. Two protocols for phenobarbital-inducible P450 and 3-methylcholanthrene-inducible P1-450 isoenzymes are described. PMID- 1902841 TI - Reversible reaction via a carbanion intermediate in the elimination of ammonia from L-histidine catalysed by histidine ammonia-lyase. AB - L-[5'-2H2]Histidine was used as a substrate to investigate the enzymatic reaction mechanism with histidine ammonia-lyase from Pseudomonas fluorescens. The study was performed to determine the exchange rate of deuterium at C-5' of the imidazole ring with solvent hydrogen relative to the net urocanic acid production. The extent of hydrogen exchange at C-5' of histidine or urocanic acid was measured by gas chromatography-mass spectrometry-selected ion monitoring, monitoring the molecular ion intensities of the respective gas chromatographic derivatives, at m/z 380 and 379 for histidine and at m/z 267 and 266 for urocanic acid. The observed hydrogen exchange at C-5' suggested a reversible mechanism via a carbanion intermediate in the reaction with histidine ammonia-lyase. PMID- 1902842 TI - Fast atom bombardment mass spectrometry as a rapid means of screening mixtures of ether-linked polar lipids from extremely halophilic archaebacteria for the presence of novel chemical structures. AB - Fast atom bombardment mass spectrometry was used to analyse intact polar ether lipids present at microgram levels in crude lipid mixtures extracted from Halobacterium halobium, Natronococcus occultus and Halobacterium marismortui. Negative-ion spectra showed the intact deprotonated lipid molecules and in some instances their sodium salts. The simplicity of the mass spectra permits the rapid screening of polar lipid mixtures for the presence of novel lipids. Additional structural information of ions with selected masses was obtained after collisionally induced decomposition. PMID- 1902843 TI - Patterns of pulsatile luteinizing hormone and follicle-stimulating hormone secretion in prepubertal (midchildhood) boys and girls and patients with idiopathic hypogonadotropic hypogonadism (Kallmann's syndrome): a study using an ultrasensitive time-resolved immunofluorometric assay. AB - To study the ontogeny of spontaneous pulsatile LH and FSH secretion before the onset of puberty, plasma LH and FSH were measured by an ultrasensitive time resolved immunoflurometric assay in 16 boys and 6 girls, aged 6.5 +/- 0.2 yr (+/- SEM; range, 4.4-8.0) with short stature. Eight male patients with idiopathic hypogonadotropic hypogonadism (Kallmann's syndrome), aged 24.1 +/- 3.4 yr, were also investigated. Blood samples were withdrawn at 10- to 20-min intervals for 12 h from 2000-0800 h. Pituitary responsiveness was assessed by a standard iv LHRH challenge test. LH and/or FSH pulses were detectable in all but two prepubertal subjects. In boys, low amplitude LH (0.16 +/- 0.06 U/L) and FSH (0.19 +/- 0.03 U/L) pulses were detectable at mean frequencies of 2.19 +/- 0.37 and 2.13 +/- 0.46 pulses/12 h, respectively. In girls, low amplitude LH (0.29 +/- 0.18 U/L) pulses, but higher (P less than 0.05 compared to boys) amplitude FSH (1.62 +/- 1.05 U/L) pulses were observed at frequencies of 1.71 +/- 0.56 and 1.67 +/- 0.53 pulses/12 h, respectively. Mean FSH in prepubertal girls (1.95 +/- 0.88 U/L) was significantly (P less than 0.05) higher than that in boys (0.46 +/- 0.07 U/L), but mean LH was not different at 0.17 +/- 0.07 and 0.10 +/- 0.03 U/L, respectively. Patients with Kallmann's syndrome had mean LH and FSH levels indistinguishable from those of prepubertal boys. Nocturnal augmentation of pulsatile LH or FSH secretion was observed in 74% of children (71% in girls and 75% in boys), but in none of the eight patients with Kallmann's syndrome. A close temporal association was observed between sleep onset and the appearance of nocturnal pulsatile gonadotropin secretion. The FSH response to exogenous LHRH in prepubertal girls was significantly greater than that in patients with Kallmann's syndrome and prepubertal boys, but LH responses were not different. Our results show that pulsatile LH and FSH secretion occurs in the majority of boys and girls in midchildhood, with a robust association with nocturnal sleep onset. Between the ages of 4-8 yr, these low amplitude and low frequency pulses are unable to activate gonadal function. The regulation of FSH secretion in prepubertal girls appears to be different from that in prepubertal boys.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1902844 TI - The effects of activin on follicle-stimulating hormone secretion and biosynthesis in human glycoprotein hormone-producing pituitary adenomas. AB - The effects of activin on pituitary FSH biosynthesis have been previously characterized using primary rat pituitary cultures; however, little is known of the effects of activin on FSH biosynthesis and secretion in human pituitary tissue. Production of intact glycoprotein hormones and free subunits is increasingly recognized in pituitary tumors; however, the regulation of gonadotropins in such tumors has not been addressed. We have investigated the effects of human recombinant activin on glycoprotein hormone biosynthesis and secretion in primary cultures of 12 human glycoprotein hormone-producing pituitary adenomas and compared this with the effects of activin in normal rat anterior pituitary cells. In 33% of the human pituitary tumors studied, significant (P less than 0.05) increases in FSH beta secretion occurred in response to incubation with 20 ng/mL activin for 24 h (19-287% stimulation), without changes in the production of intact FSH. A Northern analysis performed on cells derived from one tumor indicated that FSH beta mRNA levels increased 350% after activin treatments; however, FSH secretion did not parallel the mRNA changes. None of the human glycoprotein hormone-producing tumors significantly increased FSH secretion in response to activin. To validate the biological activity of recombinant human activin-A and to confirm time and dose conditions for the human tumor cultures, we also examined its ability to stimulate FSH production in rat pituitary cultures. Activin (20 ng/mL) added to the culture medium significantly increased FSH secretion and steady state levels of FSH beta mRNA after 24 h. These data indicate that some glycoprotein hormone-producing pituitary tumors treated with purified activin have discordant responses of intact gonadotropins and free subunit responses. In contrast to responses in normal rat gonadotrophs, FSH beta biosynthetic pathways may be uncoupled from intact FSH secretion in a subset of glycoprotein hormone-producing pituitary adenomas. PMID- 1902845 TI - Reduction of gonadotropin-releasing hormone pulse frequency is associated with subsequent selective follicle-stimulating hormone secretion in women with polycystic ovarian disease. AB - Polycystic ovarian disease (PCO) is characterized by hyperandrogenism, ovulatory dysfunction, and altered gonadotropin secretion. Mean plasma FSH concentrations are low, while LH is elevated in a majority of patients. LH pulsatile secretion has been shown to occur at rapid follicular phase frequencies (approximately one pulse per h) in PCO, suggesting persistent rapid frequency GnRH secretion in this disorder. Anovulatory women with PCO were given estradiol (E2; Estraderm skin patches) and progesterone (P; vaginal suppositories) to produce midluteal concentrations for 21 days. The aim was to determine if E2 and P would slow LH (GnRH) pulse frequency and if this would result in augmented FSH secretion and follicular development after withdrawal of E2 and P. Plasma LH was measured every 10 min for 8 h before, during (days 10 and 20), and 7 days after withdrawal of E2 and P (day 28). On each of these study days FSH was measured hourly, and E2 and P were measured every 2 h. After sampling, GnRH (25 and 250 ng/kg, iv) was given to assess pituitary responsiveness. Follicular development was monitored by vaginal ultrasound through day 34 of the study. Basal LH frequency was 8.5 +/- 0.5 pulses/8 h (mean +/- SEM). During E2 and P, LH pulse frequency fell to 3.3 +/- 1.0 (10 days) and 2.3 +/- 0.8 (20 days), 39% and 27% of the basal value, respectively, and subsequently increased to 5.6 +/- 0.7 (66% of basal) 7 days after withdrawal of E2 and P. LH pulse amplitude (basal, 7.2 +/- 1.5 IU/L) was not reduced until day 20, but remained suppressed (3.9 +/- 1.1 IU/L) on day 28. As a result, mean LH (basal, 21.0 +/- 3.5 IU/L) fell progressively during E2 and P, to 3.8 +/- 1.2 IU/L on day 20, and remained low (39% of basal) 7 days after steroid withdrawal. Mean plasma FSH (basal, 7.1 +/- 0.9 IU/L) also fell during steroid administration, but in contrast to LH, had risen to 93% of the basal value by 7 days after E2 and P. LH release in response to exogenous GnRH revealed marked initial responses which did not decrease until day 20, but remained suppressed (8% of basal) after withdrawal of E2 and P. FSH responses were also suppressed on day 20, but had increased to 75% of the basal value by day 28. Initiation of follicular development occurred in all patients, and the lead follicle measured 12.3 +/- 0.8 mm 13 days post-E2 and P. Ovulation occurred in one patient.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1902846 TI - Effects of recombinant human interleukin-2 and tumor necrosis factor-alpha with or without interferon-gamma on human thyroid tissues from patients with Graves' disease and from normal subjects xenografted into nude mice. AB - We have compared the effects of interleukin-2 (IL-2) or tumor necrosis factor alpha (TNF alpha) administration with or without interferon-gamma (IFN gamma) on Graves' and normal thyroid tissue xenografts in the nude mouse (in the absence of an intact immune system) in terms of possible functional, immunological, or histological changes. The dosages of recombinant human IL-2, TNF alpha, and IFN gamma given to each mouse were 250, 800, and 4000 U, respectively; they were injected ip daily for 6 consecutive weeks. The parameters measured included the free T4 index, thyroid autoantibodies, and mouse TSH during the course of the study. Thyroid epithelial cell (TEC) HLA-DR expression was measured in thyroid tissue before xenotransplantation and at death; in addition, light microscopic studies were carried out at those times. There were no significant differences in thyroid function between the results in unstimulated (control) animals and those obtained with cytokine administration in either group of tissues, with the exception of the group receiving TNF alpha together with IFN gamma; in this latter group, the free T4 index declined significantly 4-6 weeks after commencement of treatment in the animals with normal thyroid tissue xenografts. The reduction of thyroid function induced by the combination of IFN gamma and TNF alpha observed in normal thyroid tissue may be due to inhibition of thyroperoxidase and thyroglobulin gene transcription. However, there was no such effect on the Graves' thyroid tissue xenografts, perhaps because of down regulation of this tissue in response to cytokines, after having been released from long term in vivo immune stimulation. On the other hand, TNF alpha plus IFN gamma induced TEC HLA-DR expression on both types of thyroid xenografts at death, although IL-2 alone did not induce HLA-DR expression, and IFN gamma induced TEC significantly only on normal thyroid xenografts (but not on Graves' xenografts). In light microscopic examination, Graves' thyroid xenografts treated with IL-2 alone or TNF alpha plus IFN gamma appeared normal at death. In addition, normal thyroid xenografts treated with the same cytokines did not show discernible differences compared to those at human surgery or when the xenografts were untreated at death. We conclude that Graves' TEC did not differ from normal TEC in any significant fashion at the time of death, aside from a reduced responsiveness to the stimuli applied.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1902847 TI - Exercise induces two types of human luteal dysfunction: confirmation by urinary free progesterone. AB - We have previously reported that during 2 months of strenuous exercise, untrained young women with documented ovulatory menstrual cycles developed secondary oligoamenorrhea and luteal phase defects. In this study we tested the hypothesis that such abnormalities arise by altered neuroendocrine regulation of menstrual hormone secretion and that weight loss potentiates such effects. We supply a detailed analysis of the 20 cycles, of the total of 53, in which luteal phase abnormalities occurred. During the control month and 2 exercise months, all subjects collected daily overnight urine samples for the determination of LH, FSH, estriol (E3), and free progesterone (P) excretion by RIAs and creatinine by chemical assay. The characteristics of the abnormal luteal phase cycles were determined by comparing the excreted hormone levels and patterns during the control cycles with those of exercise cycles. The area under the curve (AUC) for each hormone was calculated for the follicular and luteal phases of each cycle. Six of the exercise cycles exhibited an inadequate luteal phase. This was characterized by a mean integrated P area of 202.4 (SEM, -61.8) nmol/day.nmol creatinine, compared with 331.7 (SEM, 64.7) during the corresponding control cycles, over a period of 9 or more days after the urinary LH peak to the onset of menses. Fourteen of the exercise cycles exhibited a short luteal phase. This was characterized by a mean integrated P area of 75.9 (30.9) nmol/day.nmol creatinine, compared to 267 (61.7) during the corresponding control cycles, over a span of 8 days or less from the urinary LH peak to the onset of menses. Additional abnormalities occurred only in the short luteal phase cycles. These included an increase in the length and AUC for E3 of the follicular phase and a decrease in the AUC of LH during the luteal phase. We conclude that the initiation of strenuous endurance training in previously ovulating untrained women frequently leads to corpus luteum dysfunction associated with insufficient P secretion and, in the case of short luteal phase cycles, decreased luteal phase length. That exercise may alter the neuroendocrine system is suggested by a delay in the ovulatory LH peak in spite of increased E3 excretion; moreover, less LH is excreted during the luteal phase. The lack of positive feedback to estrogens and decreased LH secretion during the luteal phase could compromise corpus luteum function. In contrast, decreased free P excretion was the sole abnormality noted in menstrual cycles with an inadequate luteal phase. PMID- 1902848 TI - Synaptic organization of columnar elements in the lamina of the wild type in Drosophila melanogaster. AB - The synaptic connections within the lamina, the first of the optic neuropiles underlying the insect's compound eye, have been little studied in Drosophila melanogaster until now, despite the genetic advantages of this animal. Here we report the reconstruction through its entire depth of one of the lamina modules, or cartridges, of a female wild-type Drosophila, for which a series of EM cross sections was analysed at levels extending from the retinal basement membrane to the first optic chiasma. A complete, comprehensive catalogue of the synaptic connections of all columnar elements has been compiled from this single series, confirmed from comparisons with less completely photographed cartridges. Combinations of the 12 types of cartridge neurons form divergent multiple-contact synapses (dyads, triads, and tetrads) throughout the lamina's depth. These 12 neuron types include 11 narrow-field elements (one class of receptor terminal, R1 R6, providing input to the cartridge; two types of long visual fiber from the ommatidium, R7 and R8; five types of monopolar cell, L1-5; and three types of medulla cell--two centrifugal neurons C2 and C3, and a third, T1) as well as a wide-field intrinsic or amacrine cell. Connections within the lamina formed by L4 from two adjacent cartridges (posterodorsal and posteroventral) contribute to the matrix of connections. In addition, connections of at least one other wide-field element have also been incorporated. PMID- 1902849 TI - Cytoskeletal specializations at the rod photoreceptor distal tip. AB - We have examined microtubules and microtubule-like elements within the toad rod photoreceptor outer segment in order to define regional specializations of the photoreceptor cytoskeleton. "Ciliary" microtubules were localized within the rod outer segment (ROS) by using thin section electron microscopy, immunofluorescence, and rapid-freeze deep-etch microscopy. All three methods showed that ciliary microtubules stop short of the extreme ROS distal tip, although abundant microtubule-like structures distinct from the ciliary microtubules were found within the distal 10-15 microns of the ROS tip. These heretofore undescribed "distal ROS tubules" are clustered at the clefts or incisures of the disk membrane stack and resemble microtubules in overall size and shape, although they are not closely related antigenically to tubulin. The distal ROS tubules are more abundant in green rods than red rods and vary in number during the daily light/dark cycle. Quantitation of these tubules at two time points during the light/dark cycle suggests that there are three- to fourfold more tubules in the ROS tip one hour after light onset than one hour before light onset. Retinas prevented from normal disk membrane shedding by separation of the retina from the adjacent pigment epithelium, failed to develop increased numbers of tubules after light onset. This suggests that the newly described distal ROS tubules may modulate or be modulated by light-induced interactions between the photoreceptors and pigment epithelium, such as those that occur during the disk shedding phase of membrane turnover. PMID- 1902850 TI - CT of infected bladder diverticulum. AB - A case in which pus within a bladder diverticulum simulated a deep pelvic abscess is presented. This pitfall in CT diagnosis should be considered in patients with bladder outlet obstruction with symptoms of infection. PMID- 1902851 TI - Difference in the phenotypes of bronchoalveolar lavage lymphocytes in patients with summer-type hypersensitivity pneumonitis, farmer's lung, ventilation pneumonitis, and bird fancier's lung: report of a nationwide epidemiologic study in Japan. AB - We performed a nationwide epidemiologic study of hypersensitivity pneumonitis (HP) in Japan by questionnaire and found that 835 cases of HP were recognized during the 1980s; 74.4% were summer-type HP, 8.1% farmer's lung, 4.3% ventilation pneumonitis, 4.1% bird fancier's lung, 2.3% other types, such as chemical worker's lung, and 6.8% of unknown causative agent. It was found that the CD4/CD8 ratios of bronchoalveolar lavage (BAL) lymphocytes were significantly different with the type of disease. The ratio was 0.6 +/- 0.1 (mean +/- SEM) in summer-type HP (N = 271), 4.4 +/- 0.7 in farmer's lung (N = 22), 1.6 +/- 0.3 in ventilation pneumonitis (N = 19), and 2.0 +/- 0.5 in bird fancier's lung (N = 19). In farmer's lung, the CD4/CD8 ratio in smokers was 6.2 +/- 1.9 (N = 6) in contrast with 3.4 +/- 0.7 for nonsmokers (N = 16) (p less than 0.05). It has been generally considered that the phenotypes of BAL lymphocytes in patients with HP are predominately CD8 cells. Our present results, however, indicate that the phenotypes of BAL lymphocytes vary with the type of HP, probably depending on factors such as causative agent, smoking, or staging of the disease. PMID- 1902852 TI - Monoclonal anti-T cell (T12) antibody treatment of graft-versus-host disease in severe combined immunodeficiency: targeting of antibody and activation of complement on CD8+ cytotoxic T cell surfaces. AB - We report a 6-month-old male child with severe combined immunodeficiency who received an unirradiated blood transfusion and developed acute, severe graft versus-host disease (GVHD), for which he received monoclonal anti-T cell (anti T12) antibody treatment. The GVHD was manifested by a confluent maculopapular rash and increased liver function tests and was documented by skin biopsy. Separation of peripheral blood mononuclear cells forming rosettes with sheep red blood cells revealed engrafted T cells having the nonrelated HLA type of the blood donor. The patient was treated with intravenous monoclonal anti-T12 in a dose of 0.3 mg/kg/day for 5 days. An in vivo effect of the anti-T12 was suggested by clinical improvement of his skin rash and return of the liver transaminases to the normal range. Moreover, human complement components, activated C3 and C4, were detected by fluorescence microscopy on the surfaces of the engrafted CD8+ lymphocytes on the skin biopsy specimens. Also, with a biotin-avadin assay, the presence of the anti-T12 was detected on these same cells. These studies document not only the in vivo targeting of monoclonal anti-T12 antibody to cytotoxic T cells producing GVHD but also the activation of complement on these cells. PMID- 1902853 TI - Regulation of IgM and IgD expression in human B-lineage cells. AB - IgD is thought to function primarily as an Ag receptor that is expressed, together with IgM, only on mature B lymphocytes. This differentiation stage specific expression of IgD has been well characterized in mice, where delta mRNA is detected only in mature IgM/IgD B cells. Humans, in contrast to mice, have significant levels of serum IgD, suggesting that the regulation of this isotype might differ between the two species. Therefore, we examined the regulation of both IgM and IgD expression in cell lines encompassing the spectrum of human B lineage development. Surprisingly, two species of delta mRNA could be found at all differentiation stages -from mu+ pre-B cell to IgM-secreting plasmablast. These mRNA are translated to yield the membrane and secretory forms of delta. The membrane delta-chain: secretory delta-chain ratio did not necessarily reflect the membrane mu-chain:secretory mu-chain ratio in the same cell line, implying that different mechanisms are involved in the selection of membrane vs secretory mu- and delta-chains. The delta-chains synthesized in pre-B cells were degraded, but in more mature cell types IgD could be stably expressed and secreted. Exceptions to this panlineage synthesis of delta-chains were, however, observed in two of the B cell lymphomas, where delta expression was prevented by transcriptional and posttranscriptional mechanisms. The presence of delta-chain in pre-B cells and the secretion of IgD by more mature cells suggest that IgD may have immunoregulatory roles throughout B cell differentiation. These studies also indicated that the bias toward secretory mu-chain production that occurs in human IgM secreting cells results from posttranscriptional regulation. In addition, we have identified a B cell line that synthesizes both normal-sized mu-chains and those with smaller apparent m.w. translation products of truncated mu mRNA. PMID- 1902854 TI - Complement subcomponent C1q stimulates Ig production by human B lymphocytes. AB - The regulation of Ig production by human B lymphocytes is a complex process involving interactions among B cells, APC, T lymphocytes and soluble factors including activation, growth, and differentiation factors. Components of the complement system, including C3a, C3b, C3d, and C5a, have been shown to influence various stages in this process. In this study, we demonstrate that the C1q subcomponent of complement binds to both small resting and large activated B cells and stimulates immunoglobulin production by Staphylococcus aureus Cowan activated tonsillar B lymphocytes. This effect is present whether C1q is added to the B cells either at the beginning or near the end of a 7-day culture period and is not associated with enhancement of proliferation. The C1q stimulation of Ig production is, however, associated with increased steady state levels of mRNA for the mu Ig H chain. Furthermore, C1q stimulated IgM production by the human B cell line SKW 6.4, which is capable of secreting IgM in response to B cell differentiation factors (BCDF). SLE is a disorder frequently associated with polyclonal activation of B lymphocytes. We studied the effect of C1q on B cells from two patients with this disorder and one with an SLE-like illness, all selected for the predominance of either IgM or IgG in serum. Spontaneous or BCDF stimulated Ig secretion was of the isotype predominant in vivo, whereas C1q selectively stimulated B cells to produce the other isotype (IgG vs IgM). Thus, C1q interacts with B lymphocytes in a manner distinct from that of BCDF found in mixed lymphocyte supernatants. C1q may be an important factor influencing the production of Ig by B lymphocytes in normal individuals and in patients with abnormalities of B cell activity. PMID- 1902855 TI - Inhibition of colony-stimulating factor-stimulated macrophage proliferation by tumor necrosis factor-alpha, IFN-gamma, and lipopolysaccharide is not due to a general loss of responsiveness to growth factor. AB - The role of stimulatory factors, such as the CSF, in the regulation of hemopoiesis has been extensively documented. Less is known of the negative regulators of hemopoiesis. In this report, we show that the macrophage activating agents, TNF-alpha, IFN-gamma, and LPS, are all potent inhibitors of CSF-1 stimulated murine bone marrow-derived macrophage (BMM) DNA synthesis and increase in cell numbers. The inhibitory effects of TNF-alpha and IFN-gamma do not appear to be due to endotoxin contamination in the recombinant cytokine preparations. The inhibition of proliferation is reversible and is not due to a general loss of growth factor responsiveness, inasmuch as the three agents do not inhibit CSF-1 stimulated BMM survival, protein synthesis, or fluid phase pinocytosis. Because TNF-alpha and LPS are known to rapidly and potently down-modulate CSF-1 receptor levels in BMM, the results also suggest that low levels of receptor occupancy are sufficient for biological responses to CSF-1. The inhibitory effects of TNF alpha, IFN-gamma, or LPS were also seen when granulocyte-macrophage-CSF or IL-3 was used to stimulate BMM DNA synthesis. The results suggest that TNF-alpha, IFN gamma, and LPS appear to be inhibiting CSF-stimulated proliferation by acting at a post-receptor level, possibly by regulation of some critical event(s) in the mitogenic signaling pathway. PMID- 1902856 TI - Abrogation of glucocorticoid-mediated inhibition of T cell proliferation by the synergistic action of IL-1, IL-6, and IFN-gamma. AB - Glucocorticoids (GCS) inhibit the transcription of multiple activation-associated cytokine genes. By Northern blot analysis now we demonstrate that antiproliferative concentrations of dexamethasone and 6 alpha-methylprednisolone block mitogen-induced IL-2 gene expression in human peripheral blood mononuclear leukocytes in a concentration-dependent fashion. In addition, using a mitogen induced proliferation assay of human peripheral blood mononuclear leukocytes, we show that GCS-mediated anti-proliferative effects are not blocked by rIL-1, rIL 2, rIL-3, rIL-4, rIL-5, rIL-6, rTNF-alpha, rTNF-beta, and rIFN-gamma, individually at 1 to 1000 U/ml, but are totally abrogated, in a concentration dependent fashion, by the combination of rIL-1, rIL-6, and rIFN-gamma (25 to 50 U/ml for each cytokine). Thus, blockade of cytokine expression is the primary mechanism by which GCS inhibit mitogen-driven and alloantigen-induced T cell proliferation. The immunosuppressive effects of GCS are almost certainly exacted at the level of cytokine gene transcription. PMID- 1902857 TI - Differential control of IFN-gamma and IL-2 production during Trypanosoma cruzi infection. AB - In murine infection with Trypanosoma cruzi, immune responsiveness to parasite and non-parasite Ag becomes suppressed during the acute phase of infection, and this suppression is known to extend to the production of IL-2. To determine whether suppression of lymphokine production was specific for IL-2, or was a generalized phenomenon involving suppressed production of other lymphokines, we have begun an investigation of the ability of mice to produce of a number of lymphokines during infection, initially addressing this question by studying IFN-gamma production. Supernatants from Con A-stimulated spleen cells from infected resistant (C57B1/6) and susceptible (C3H) mice were assayed for IFN-gamma. Supernatants known to be suppressed with respect to IL-2 production from both mouse strains contained IFN gamma at or above that of supernatants from normal spleen cells. Samples were assayed in an IFN bioassay to ensure that the IFN-gamma detected by ELISA was biologically active. Thus, suppression during T. cruzi infection does not extend to the production of all lymphokines. The stimulation of IFN-gamma production was confirmed by detection of IFN-gamma mRNA in unstimulated spleen cells from infected animals, and in Con A, Con A + PMA, and in some cases, parasite Ag stimulated spleen cells from infected animals. IFN-gamma mRNA levels in mitogen stimulated spleen cells equalled or exceeded those found in similarly stimulated normal cells. In contrast, stimulated spleen cells from infected animals had reduced levels of IL-2 mRNA relative to normal spleen cells. Thus at both the protein and mRNA level, IFN-gamma production is stimulated by T. cruzi infection, whereas IL-2 production is suppressed. Serum IFN-gamma in infected C57B1/6 and C3H mice was detected 8 days after infection, peaked on day 20 of infection, and subsequently fell, but remained detectable at low levels throughout the life of infected mice. Infected animals were depleted of cell populations known to be capable of producing IFN-gamma, and Thy-1+, CD4-, CD8-, NK- cells, and to a lesser degree, CD4+ and CD8+ cells were found to be responsible for the production of IFN-gamma during infection. We also report that IL-2 can induce IFN gamma production in vitro and in vivo by spleen cells from infected animals, and that IL-2 can synergize with epimastigote or trypomastigote antigen to produce high levels of IFN-gamma comparable to those found in supernatants from mitogen stimulated cells. PMID- 1902858 TI - Endogenous IFN-gamma is required for resistance to acute Trypanosoma cruzi infection in mice. AB - In order to study the role of endogenous IFN-gamma in Trypanosoma cruzi infection in mice, a potent murine IFN-gamma-specific mAb was injected i.p. on days -1, 7, and 14, relative to infection. Irrespective of the parasite inocula (100 or 25,000), groups of antibody-treated mice had significantly greater cumulative mortality rates than did appropriate controls. In antibody-treated mice, mean survival times were also significantly shorter, and maximum mean parasitemia levels were significantly higher, than in controls. Moreover, the number of amastigote nests in tissues was higher than in control mice and attained a maximum at the same time as parasitemia. As evident from kinetic studies of neutralizing activity, injected mAb were rapidly consumed in infected, but not in noninfected, mice, which is suggestive of massive IFN-gamma production during the early parasitemic phase of the disease. Nevertheless, IFN-gamma remained undetectable in the sera of infected but untreated mice. Unexpectedly, however, a peak of IFN-like antiviral activity, characterizable as a mixture of IFN-gamma and IFN-beta, appeared in mAb-treated mice that survived to infection at a time when neutralizing activity of injected mAb had drastically decreased in the circulation. We hypothesize that this high level of artificially induced endogenous IFN-gamma, not neutralized by the amounts of injected mAb, was due to the more intense parasite multiplication occurring in mAb-treated mice, which in turn may have induced an increased amount of various cytokines. TNF-alpha was not found in the serum of our mice. The humoral immune response entered its exponential phase at a time point later than that when protection by endogenous IFN-gamma was evident. Treatment with IFN-gamma-specific antibody, as applied in our study, failed to affect the level of different Ig isotypes or of T. cruzi specific antibodies. Our study clearly indicates that IFN-gamma is produced early in acute T. cruzi infection and exerts a protective effect that is probably independent from the humoral immune response. PMID- 1902859 TI - Position of the rearranged V kappa and its 5' flanking sequences determines the location of somatic mutations in the J kappa locus. AB - Somatic hypermutation is known to occur in the VJ kappa exon and its flanking sequences, yet little is known about the hypermutation mechanism or its exact target within the rearranged locus. Mutations may occur at the same frequency, spanning a region from the leader intron to 3' of J kappa 5, regardless of which J is chosen for VJ rearrangement. Another possibility is that mutations may be limited to the rearranged VJ kappa and its immediate flanking sequences. To distinguish between these possibilities, the JC introns of 21 alleles with V kappa rearranged to J kappa 1 were sequenced, and mutations were located. The frequency of mutations was determined for different sections of the intron and compared with the frequencies of mutations found in the JC intron of a set of VJ kappa 5 alleles. The results showed that mutations were concentrated in and around the rearranged VJ, regardless of whether J kappa 1 or J kappa 5 was used. These data imply that the hypermutational mechanism focuses on rearranged V genes. PMID- 1902860 TI - Specific release of granulocyte-macrophage colony-stimulating factor, tumor necrosis factor-alpha, and IFN-gamma by human tumor-infiltrating lymphocytes after autologous tumor stimulation. AB - Tumor-infiltrating lymphocytes (TIL) have been cultured from a variety of human tumors, and some melanoma TIL have demonstrated specific, MHC-restricted recognition of autologous tumor in short term lysis assays. The current study investigates cytokine release by TIL as an indicator of specific tumor recognition. We have identified two of four melanoma and one of seven breast carcinoma TIL cultures that specifically release granulocyte-macrophage-CSF, TNF alpha, and IFN-gamma after autologous tumor stimulation. The other cultures either do not secrete cytokine or secrete cytokine in a nonspecific fashion. The amount of specific cytokine released is directly related to the number of TIL and stimulating tumor cells. Studies of TIL, from two melanoma patients, separated into CD4+ and CD8+ populations revealed that CD8+ cells were responsible for virtually all of the specific cytokine secretion, although both populations released cytokines when activated by immobilized anti-CD3 antibody. Specific cytokine release by CD8+ TIL was inhibited by anti-MHC class I mAb. Specific cytokine release was also detected from a CD4+ breast cancer TIL culture, and this was inhibited by anti-MHC class II mAb. The clinical significance of this specific mode of immune antitumor reactivity is currently under investigation. PMID- 1902861 TI - Cerebrospinal fluid shunt infection: an unusual case. PMID- 1902862 TI - Low rate of vaginal carriage of Listeria monocytogenes. PMID- 1902863 TI - Sensitivity testing of Pseudomonas aeruginosa against netilmicin and gentamicin: aminoglycosides revisited. PMID- 1902864 TI - Effect of dietary fish oil on development and selected functions of murine inflammatory macrophages. AB - Inflammatory macrophages from mice fed diets containing menhaden fish oil (MFO) have a reduced capacity for cytotoxicity of mastocytoma cells upon activation with interferon-gamma (IFN gamma) and lipopolysaccharide due to an altered responsiveness to IFN gamma. In an effort to elucidate further how dietary MFO effects macrophage function, we have studied the maturation of inflammatory macrophages from mice fed MFO compared with mice fed safflower oil (SFO) using several processes that serve as markers of the activational state. No significant differences in the recruitment or percentage of peritoneal exudate cells as macrophages after thioglycollate injection and no differences in spreading, binding, or phagocytosis of sheep erythrocytes or phagocytosis of yeast by inflammatory macrophages were observed when the dietary groups were compared. However, MFO macrophages had an altered capacity for peroxide release when stimulated with unopsonized zymosan (10-200 micrograms/ml). Furthermore, to elucidate how MFO feeding could alter IFN gamma-induced responses of inflammatory macrophages, we assessed phorbol-12-myristate-13-acetate-induced hydrogen peroxide production and expression of class II MHC determinants (Ia). There were no differences between macrophages from mice fed the two diets with respect to the production of peroxide when they were preincubated with 0.1-10 U/ml of IFN gamma. However, MFO macrophages had greater peroxide production after enhancement with 100 U/ml of IFN gamma. With respect to Ia induction, the percentage of macrophages responding to IFN gamma was not altered by diet, and there were no differences in expression of Ia induced by 24 hr exposure to IFN gamma. Thus the differential effect of MFO compared with SFO is probably mediated not by an alteration in the maturation of inflammatory macrophages but rather through the alteration of IFN gamma-induced functions such as peroxide production. PMID- 1902865 TI - Activated macrophage conditioned medium: identification of the soluble factors inducing cytotoxicity and the L-arginine dependent effector mechanism. AB - Conditioned medium (CM) from cultures of cytotoxic activated macrophages causes inhibition of mitochondrial respiration, DNA synthesis, and aconitase activity in murine EMT-6 mammary adenocarcinoma cells by an L-arginine dependent effector mechanism. CM induces cytotoxicity and nitrite synthesis in EMT-6 cells in a dose dependent manner. We have identified the soluble factors in CM that induce cytotoxicity and synthesis of inorganic nitrogen oxides from L-arginine by EMT-6 cells. Using functional inhibition experiments, the activity of lipopolysaccharide (LPS), tumor necrosis factor alpha (TNF alpha), and interferon gamma (IFN gamma) in CM was investigated. The LPS inhibitor polymyxin B and TNF alpha antibody produced a modest decrease in nitrite production, while IFN gamma antibody markedly inhibited both nitrite production and cytostasis. Simultaneous treatment with polymyxin B, TNF alpha antibody, and IFN gamma antibody reduced EMT-6 cell nitrite production by 81%, and cytostasis by 74%. By Western blot, IFN gamma and TNF alpha were shown to be present in CM. When CM was subjected to hydrophobic interaction chromatography, a single peak of activity was eluted, and Western blot showed that the active fractions contained IFN gamma. Furthermore, IFN gamma antibody neutralized the activity in these chromatographic fractions. We conclude that induction of inorganic nitrogen oxide synthesis from L-arginine by the synergistic combination of IFN gamma, TNF alpha, and LPS accounts for most of the biologic activity of CM, and that IFN gamma is the major priming factor. PMID- 1902866 TI - Intravenous immunoglobulin prophylaxis for infection in very low birth-weight infants. AB - The effectiveness of intravenous immunoglobulin for prevention of sepsis in very low birth weight infants was studied on 102 neonates at the Children Hospital, Bangkok from February 1988 to February 1990. Infants were randomly allocated into 3 groups of 35 each. Group I and group II received 250 mg/kg and 500 mg/kg of immunoglobulin intravenously respectively within four hours of life. Group III was not given immunoglobulin and served as the control group. It was found that during the early neonatal period the infection rate of group I (14.7%) and group II (14.7%) was significantly lower than that of group III (38.2%). There was no difference in the infection rate of group I and group II. The mortality rate was also higher in group III than in group I and group II. It suggested that the intravenous immunoglobulin dosage of 250 mg per kilogram body weight is effective as well as dosage of 500 mg per kilogram body weight in prevention of sepsis in very low birth weight infants during the early neonatal period. PMID- 1902867 TI - Nutritional status of low socioeconomic school children at Srakaew Temple, Ang Thong. AB - Nutritional deficiency in school children is one of the major health problems in Thailand. This study was undertaken to investigate the nutritional status in 240 poor adopted school children who were classified as low socioeconomic. Biochemical parameters were measured for detecting early signs of nutritional deficiency before the clinical signs developed. Serum protein and albumin levels did not show statistically significant different between the protein energy deficiency group and the normal group (p greater than 0.05, p greater than 0.05). Fifty-four point five per cent of these children showed sign of vitamin B2 deficiency, 13.6 per cent of them with activity coefficient greater than 1.8, indicating the low protein intake of this group of children. However, there was no statistically significant difference in the vitamin B2 level between the normal and protein calorie malnutrition groups (p greater than 0.05). According to our study, the prevalence of anemia among these children was 53.1 per cent. Moreover, the difference in hemoglobin level between these two groups was found with statistical significance (p less than 0.05). PMID- 1902868 TI - Hypo-fibrinolysis in patients with hypertension and elevated cholesterol. AB - To test the hypothesis that increased blood pressure and hyperlipidaemia result in changes in the fibrinolytic system, 84 subjects with both hypertension and elevated serum cholesterol levels (the high risk group) were compared with 55 controls matched with respect to age, sex and body mass index (BMI). Plasminogen activator inhibitor (PAI-1), and tissue plasminogen activator (tPA) antigen and activity were measured before and after venous occlusion. In the high risk group, tPA activity was significantly lower both before and after venous occlusion and PAI-1 levels were significantly higher. In a multivariate analysis the triglyceride levels, diastolic blood pressure and cholesterol levels were independently associated with the PAI-1 levels. Diastolic blood pressure was independently and inversely associated with resting tPA activity. We conclude that patients with hypertension and hyperlipidaemia have a reduced activity of the fibrinolytic system, an effect which is unrelated to differences in age, sex, smoking or BMI. PMID- 1902869 TI - Effect of fish diet versus meat diet on blood lipids, coagulation and fibrinolysis in healthy young men. AB - Twelve healthy young men followed a 10-d controlled diet that included 210 g of fatty fish d-1. The diet was repeated after 18 d, but with lean meat substituted for fish. Blood samples were collected for assessment of serum lipids and haemostatic variables in the plasma. Both experimental diets caused serum triglycerides and plasma factor VIIc to decline to the same extent. The meat diet was also associated with significant changes in plasma levels of tissue plasminogen activator (t-PA) antigen. PA inhibitor type I (PAI-1) antigen, PAI activity, and t-PA activity of the euglobulin fraction of plasma. The fish diet left these variables unchanged from initial values. Thus, in a paired comparison of the two diets, the fish diet was associated with higher levels of t-PA antigen (5.4 vs. 4.7 g ml-1), which is considered to be beneficial with regard to prevention of cardiovascular disease. However, the fish diet was concurrently associated with the putative unfavourable higher levels of PAI-1 antigen (3.0 vs. 1.2 ng ml-1) and PAI activity (6.1 vs. 3.2 IU ml-1), and lower t-PA activity (80 vs. 140 mIU ml-1). Thus it is unclear which of the two diets has the greatest potential in the prevention of cardiovascular disease. PMID- 1902870 TI - Scuttling the squeeze. Squashing the incipient Florida State medical cost containment scam. PMID- 1902872 TI - Recombinant cholinergic differentiation factor (leukemia inhibitory factor) regulates sympathetic neuron phenotype by alterations in the size and amounts of neuropeptide mRNAs. AB - The cholinergic differentiation factor (CDF) in heart cells is identical to leukemia inhibitory factor (LIF). Recombinant CDF/LIF was shown to alter dramatically neurotransmitter production as well as the levels of several neuropeptides in cultured rat sympathetic neurons. Here it is shown that these changes are likely to be caused by alterations in the mRNA for these proteins and peptides. Growth in 1 nM recombinant CDF/LIF induces mRNA for acetyl CoA: choline O-acetyltransferase [EC 2.3.1.6; choline acetyltransferase (ChAT)], somatostatin (SOM), substance P, and vasoactive intestinal polypeptide while lowering mRNA levels of tyrosine hydroxylase (EC 1.14.16.2) and neuropeptide Y (NPY). In addition, the sizes of the mRNAs for ChAT, SOM, and NPY are larger after recombinant CDF/LIF treatment. PMID- 1902871 TI - Modification of brain guanine nucleotide-binding regulatory proteins by tryptamine-4,5-dione, a neurotoxic derivative of serotonin. AB - We have recently characterized a novel oxidation product of serotonin (5 hydroxytryptamine, 5-HT), tryptamine-4,5-dione, which increases 5-HT efflux from striatum and hippocampus and causes selective neuronal death. Exposure of striatal synaptosomes or the major brain guanine nucleotide-binding regulatory proteins Gi and Go to [3H]tryptamine-4,5-dione resulted in the radiolabeling of a major band with an apparent molecular mass equivalent to that of the alpha subunits of Gi and Go (approximately 40,000). The binding of [35S]guanosine-5'-O (3-thiotriphosphate) ([35S]GTP-gamma-S) to Gi and Go and pertussis toxin catalyzed [32P]ADP-ribosylation of the G protein alpha subunits were both inhibited in a dose-dependent manner by tryptamine-4,5-dione. Thus, neurotoxins such as tryptamine-4,5-dione may exert their effects through specific interactions with G proteins. PMID- 1902873 TI - Synapsin I and Synaptophysin expression during ontogenesis of the mouse peripheral vestibular system. AB - Synapsin I and Synaptophysin are selectively localized in axonal endings of CNS neurons where they are associated with small synaptic vesicle membranes. The development of expression of these 2 proteins was studied by immunocytochemistry during ontogenesis of the peripheral vestibular system in the mouse. Both proteins are localized in vestibular ganglion neurons and in their peripheral sensory extensions as early as gestational day 14. While the entire periphery of these fibers is labeled during embryogenesis, both proteins are subject to relocation during the postnatal maturation of these fibers. In the mature vestibular receptors they disappear from the fibers themselves but are found concentrated in their intraepithelial endings and in the neuronal cell body. These observations show that the distribution pattern of Synapsin I and Synaptophysin in peripheral extensions of vestibular afferent neurons during development is identical to that described in axonal processes of CNS neurons. This suggests that the peripheral processes of the vestibular afferent neurons present structural and biochemical characteristics of axons. These characteristics are consistent with a bimodal sensory and secretory function of mature endings. PMID- 1902875 TI - Proteinases secreted by human mononuclear phagocytes. AB - Human mononuclear phagocytes express an array of serine and metal dependent proteinases that are under complex developmental control and are also highly regulated by physiologic and pharmacologic stimuli. Monocytes contain the intracellular serine proteinases, elastase and cathepsin G, but have little metalloproteinase secretory capacity. Macrophages, on the other hand, produce predominantly metalloproteinases. Phorbol induced differentiation of promonocyte like U937 cells into more mature mononuclear phagocytes results in transcriptional suppression of cathepsin G and temporally delayed onset of collagenase transcription. Mature macrophages upregulate metalloproteinase synthesis in response to lipopolysaccharide and phorbol myristic acetate; expression is downregulated with interferon gamma and dexamethasone. Thus, during the development of the mononuclear phagocyte, stores of serine proteinases are replaced by regulated secretion of metalloproteinases. These alterations may reflect changing roles of these cells in extracellular matrix degradation. PMID- 1902874 TI - Regulation of plasminogen activator activity in arthritic joints. AB - The plasminogen activator (PA)/plasmin system has been implicated in the inflammation and connective tissue remodelling occurring in arthritic joints. PA activity is detected in cultures of human monocytes, synoviocytes and chondrocytes and can be regulated by a variety of cytokines found in diseased joints; PA inhibitors (PAI-1 and/or PAI-2) are also produced by these cells. We have shown that human monocytes can synthesize both urokinase-type PA (u-PA) and tissue-type PA (t-PA). One cytokine present in rheumatoid synovial fluids, granulocyte macrophage colony stimulating factor (GM-CSF), stimulates monocyte u PA production; since this cytokine can also be produced by activated monocytes and other cell types in joints, than a "CSF network" can be produced leading to u PA production. Another monocyte cytokine, interleukin 1, causes human synoviocytes to increase their u-PA expression, a response which can be dependent on the presence of endogenous cyclooxygenase products; this cytokine also causes human chondrocytes and cartilage tissue to produce increased u-PA and t-PA activity, i.e., under conditions during which cartilage is resorbed. PMID- 1902876 TI - Recovery rate of malnourished children in Zaria, Nigeria. PMID- 1902877 TI - [Surface phenotypic diversity of CD4 or CD8 in ATL]. AB - A 51-year-old woman was admitted to our hospital complaining of lymphadenopathy in June, 1987. Lymph node biopsy revealed diffuse lymphoma, mixed cell type according to the LSG classification. On hematological examinations, leukocyte has counted 12,400/microliters, of which 15% abnormal lymphocytes containing human T cell lymphotropic virus type-1 (HTLV-1) proviral DNA into the cellular DNA. She was diagnosed as adult T-cell leukemia (ATL). The abnormal lymphocytes in the peripheral blood expressed CD4 but lymph node cells expressed CD8. Thirty months after initial diagnosis, abnormal lymphocytes began to increased and reached 30,500/microliters. Surface phenotype of abnormal lymphocytes changed CD3+ CD4+ CD8- OKla1+ to CD3- CD4- CD8- OKla1-. This change is considered to show the surface phenotypic diversity in ATL cells. PMID- 1902878 TI - [Pure red cell aplasia and pseudothrombocytopenia associated with hepatitis A]. AB - We report a rare case who developed pure red cell aplasia (PRCA) and pseudothrombocytopenia associated with hepatitis. A 50-year-old woman was admitted to the hospital because of acute hepatitis A. On the 22nd hospital day, normocytic normochromic anemia without reticulocytosis was developed. A bone marrow aspirate revealed erythroid hypoplasia with a small percentage of proerythroblasts and basophilic erythroblasts, but almost complete absence of polychromatophilic and orthochromic erythroblasts. This case was diagnosed as PRCA characterized by the maturation arrest of erythropoiesis. Anemia was spontaneously recovered following marked reticulocytosis. Afterward, transient EDTA-dependent pseudothrombocytopenia developed for 3 months. The serum taken during the acute phase of clearly inhibited BFU-E colony formation. This data suggests that some humoral factor in the serum of this patient may be involved in the pathogenesis of PRCA. PMID- 1902879 TI - [Increased levels of beta 2-microglobulin in peripheral blood mononuclear cells and hepatocytes in patients with chronic hepatitis type B]. AB - The levels of beta 2-microglobulin (beta 2m) in peripheral blood mononuclear cells (PBMC) and livers from patients with chronic liver diseases type B were measured. Beta 2m of liver and PBMC in chronic active hepatitis was higher than those of controls (p less than 0.01, p less than 0.01). beta 2m of PBMC are directly proportional to those of livers (r = 0.746), beta 2m levels of PBMC in patients with chronic active hepatitis during the exacerbation of hepatitis was higher than those of remission of hepatitis. The levels of beta 2m in PBMC in vivo, was significantly increased during either interferon alpha or beta administration. Interferon-gamma positive cells in the liver were exacted in the beta 2m increased group of chronic hepatitis type B. INF-gamma production in the lymphocyte of livers, may play an important role in the occurrence of liver injury in patients with chronic hepatitis type B. PMID- 1902880 TI - Dissolution of bile duct stones by a hydrophilized glyceromonooctanoin-bile-acid EDTA emulsion. AB - The clinical suitability of conventional glyceromonooctanoin (GMOC) and ethylenediaminetetraacetic acid (EDTA) containing solvents for the dissolution of common bile duct stones is questionable. To improve the solvent-stone contact and the miscibility with bile, GMOC was hydrophilized by the addition of polyethyleneglycol-caprylglyceride, polyethyleneglycol-sorbitan-etheroleyl-ester, and polyethyleneglycol-sorbitanlauryl-ester (PEG-GMOC). This product was mixed with a bile acid-EDTA (BA-EDTA) solution in a ratio of 1:2 (v/v) for cholesterol solubilizing and calcium complexing capacities. To determine clinical efficiency, the new solvent was infused via a nasobiliary tube in 16 patients with endoscopically nonextractable common bile duct stones and compared with a group of 16 patients treated with an alternating GMOC/BA-EDTA regimen. Continuous perfusion with PEG-GMOC-BA-EDTA led to a total (12 patients) or partial (3 patients) disappearance of the stones within 2-15 days. Similarly, alternating GMOC and BA-EDTA treatment dissolved the stones in 12 patients. The average volume of PEG-GMOC-BA-EDTA infused contained only 27% of the GMOC applied during the alternating therapeutic regime. This reduction of the GMOC dose was associated with a significant reduction of adverse effects such as emesis, diarrhea and biliary pain. We concluded that GMOC is equally efficient in the new hydrophilized form but it is clearly superior as far as side effects are concerned. In all, this supports its clinical suitability for the dissolution treatment of common bile duct stones. PMID- 1902881 TI - Long-term treatment with SMS 201-995 in resistant acromegaly: effectiveness of high doses and continuous subcutaneous infusion. AB - Seventeen patients (8 women and 9 men) resistant to all other forms of therapy were treated with the somatostatin analogue SMS 201-995 (octreotide, Sandostatin). The duration of treatment ranged from 1 to 5 years. Mean GH levels of only 4 patients were suppressed under 5 micrograms/L during an 8 h serum profile with the standard dose of 0.1 mg 2 or 3 times daily. This standard dose suppressed mean GH levels in 10 other patients more than 50% of baseline, but for optimal effect higher doses up to 1.5 mg, 4 daily injections or continuous subcutaneous infusion (CSI) were needed. Octreotide had no influence on GH secretion in 3 patients. Suppression of mean GH levels under 5 micrograms/L was achieved in 10 patients. Normalization of insulin-like growth factor I (IGF-I) occurred in only 5 patients. Altogether, therapy with SMS 201-995 reduced GH levels from 23.8 +/- 32.2 micrograms/L (mean +/- SD) to 6.7 +/- 5.0 micrograms/L by 71.8% and IGF-I levels from 7.9 +/- 3.1 U/ml to 3.2 +/- 1.6 U/ml by 59.5%. We conclude that 1) treatment with SMS 201-995 in patients resistant to other forms of therapy may be less successful than previously reported for heterogenous groups of patients; 2) the dose regimen must be adapted to the individual patient for optimal effect and most of our patients needed higher doses than 300 micrograms daily; 3) 4 or maybe more daily injections or CSI seem to be most effective; and 4) in a minority of patients SMS has no influence on GH-secretion. PMID- 1902882 TI - McArdle's disease: successful symptomatic therapy by high dose oral administration of ribose. PMID- 1902883 TI - [Standards for functional service]. PMID- 1902884 TI - [Experiences with nursing standards]. PMID- 1902885 TI - [University studies for teachers in allied health professions. The study course in medical pedagogics at the Humboldt University in Berlin]. PMID- 1902886 TI - [Quality assurance in nursing in a short overview]. PMID- 1902887 TI - [Scientific teacher education as a condition for professional teaching of nursing]. PMID- 1902888 TI - [The dangerous course of a new discipline]. PMID- 1902889 TI - [Possibilities and limits of bone marrow transplantation]. PMID- 1902890 TI - [Prevention of infection in endoscopy. First position of the Endoscopy Work Group]. PMID- 1902891 TI - [Standards in nursing. A personal position on theoretical expectations and practical applications]. PMID- 1902892 TI - [The employer's right to question]. PMID- 1902893 TI - [The right of co-determination of the Works Committee in case of changes of the service schedule]. PMID- 1902894 TI - [Legal aspects of the responsibility of nurses in clinical testing of drugs]. PMID- 1902895 TI - [Decision of the state labor court on stand-by services]. PMID- 1902896 TI - [Development in nursing--guidance of the nurses. Ideas for better cooperation in the hospital]. PMID- 1902897 TI - [Recording of working time. Check list for computer systems]. PMID- 1902899 TI - [We nurse for health, not for fitness in war]. PMID- 1902900 TI - [The importance of the nursing process for nursing]. PMID- 1902898 TI - [Dedication of the educational center; Federal Service Medal for Margit Frantz]. PMID- 1902901 TI - [Ruling on standards and principles for manpower in intramural psychiatry. (Psychiatric personnel ruling) of the federal government from 18 December 1990]. PMID- 1902902 TI - [Determination of the need for personnel]. PMID- 1902903 TI - [Stresses in the care of AIDS patients. Report on an inquiry from nurses]. PMID- 1902904 TI - [AIDS--a challenge to nursing]. PMID- 1902905 TI - [Commission of European xx associations--advisory board on the formation of nurses: guidelines on the reduction of the chasm between theory and practice in the education of nurses for general care]. PMID- 1902906 TI - [To help and to approach each other]. PMID- 1902907 TI - Update on theophylline for asthma in children. PMID- 1902908 TI - Effect of glutathione on mitomycin C-induced micronuclei in bone marrow erythrocytes of Swiss albino mice. AB - The antimutagenic potential of glutathione (GSH) on mitomycin C (MMC)-induced micronuclei was evaluated in Swiss albino mice using the in vivo bone marrow micronucleus test. Six groups of animals were maintained simultaneously. The first group received distilled water only, the second group of animals received 2 mg/kg MMC and the third group was administered 4 doses of GSH, i.e., 20, 40, 80 and 160 mg/kg. The fourth group of animals received GSH and MMC simultaneously. The fifth and sixth groups received a cumulative dose of GSH followed by MMC after 24 h. The fifth group of animals were killed 6 h after the administration of MMC, while the sixth group were killed 24 h after the administration of MMC. The results clearly show a statistically significant increase in micronuclei in MMC-treated animals and also in animals that received GSH followed by MMC. However, there was a decrease in micronuclei in animals that received GSH and MMC simultaneously. The results clearly indicate that GSH exhibits an antimutagenic property in the presence of MMC. It is also observed the treatment with GSH prior to MMC does have some protective effect. PMID- 1902909 TI - Genotoxic effects of the drinking water mutagen 3-chloro-4-(dichloromethyl)-5 hydroxy-2[5H]-furanone (MX) in mammalian cells in vitro and in rats in vivo. AB - The potent bacterial mutagen 3-chloro-4-(dichloromethyl)-5-hydroxy-2[5H]- furanone) (MX), which is formed during chlorination of drinking water and accounts for about one third of the Ames mutagenicity of tap water, has been studied with respect to its genotoxicity in vitro and in vivo. Treatment with 30 300 microM MX (1 h) induced DNA damage in a concentration-dependent manner in suspensions of rat hepatocytes, as measured by an automated alkaline elution system. The effect was similar in hepatocytes from PCB-induced and uninduced rats. DNA damage was induced in V79 Chinese hamster cells and in isolated rat testicular cells, at the same concentration level as in hepatocytes. Pretreating testicular cells with diethylmaleate, which depletes 85% of cellular glutathione, had no significant effect on the DNA damage induced by MX. The treatment conditions used in the alkaline elution experiments were not cytotoxic to any of the cell types used, as determined by trypan blue exclusion. V79 cells exposed to 2-5 microM MX (2 h) showed an increased frequency of sister-chromatid exchanges (SCE) whereas no significant effect on HGPRT mutation induction was observed. Higher concentrations (greater than 10 microM, 2 h) apparently blocked cell division. The data indicate that MX can react directly with DNA or that MX is metabolized to an ultimate mutagen via some enzyme which is common in mammalian cells. The in vivo experiments showed no evidence of genotoxicity after intraperitoneal (18 mg/kg, 1 h) or oral (18, 63 or 125 mg/kg, 1 h) administration of MX, as measured by alkaline elution, in any of the following organs: the pyloric part of the stomach, the duodenum, colon ascendens, liver, kidney, lung, bone marrow, urinary bladder and the testes. In conclusion, MX is a direct-acting genotoxicant in vitro but no in vivo genotoxicity was detected. PMID- 1902910 TI - Genotoxicity evaluation of five tricyclic antidepressants in the wing somatic mutation and recombination test in Drosophila melanogaster. AB - Five tricyclic antidepressants were tested for genotoxicity using the somatic mutation and recombination test (SMART) in wing cells of Drosophila melanogaster. Three-day-old larvae trans-heterozygous for 2 linked recessive wing hair mutants (multiple wing hairs and flare) were fed the test compounds in water mixed with a standard dry food for 48 h. Wings of the emerging adult flies were scored for the presence of spots of mutant cells which can be the consequence of either somatic mutation or mitotic recombination. Desipramine and imipramine were clearly genotoxic at concentrations above 1 mM whereas amitriptyline, nortriptyline and protriptyline were not genotoxic at concentrations up to 100 mM. This seems to implicate the nitrogen atom at position 5 in the 7-membered ring of the tricyclic molecule as being responsible for the genotoxic property of the compounds in Drosophila. PMID- 1902911 TI - Microbiological characterizations by FT-IR spectroscopy. AB - Infrared signals of microorganisms are highly specific fingerprint-like patterns that can be used for probing the identity of microorganisms. The simplicity and versatility of Fourier-transform infrared spectroscopy (FT-IR) makes it a versatile technique for rapid differentiation, classification, identification and large-scale screening at the subspecies level. PMID- 1902912 TI - [Diphosphonates in the treatment of osteoporosis]. PMID- 1902913 TI - [The breathing casette; a useful aide in hyperventilation]. AB - The breathing cassette (Hyperfree) was tested on 10 persons suffering from hyperventilation syndrome. Each subject performed a hyperventilation provocation of two minutes on three separate occasions. Immediately after the hyperventilation provocation the subject was asked to terminate the hyperventilation, firstly with no aid at all, later using a plastic bag or the breathing cassette. The %vol. CO2 in the exhaled air was recorded with a capnograph. The use of the plastic bag and the breathing cassette resulted in an equal restoration of the %vol. CO2. After using the cassette for six weeks the patients completed a questionnaire. All patients stated that they intended to continue using the breathing cassette, and that it was easy and handy to use. Most patients carried the cassette always with them, since it made them feel comfortable. PMID- 1902914 TI - Correlation of regional cerebral blood flow and blood flow velocity in normal volunteers and patients with cerebro-vascular disease. AB - Transcranial Doppler sonography and measurement of regional cerebral blood flow using the Xenon133-inhalation technique have been used simultaneously in 10 normal volunteers and 13 patients with acute-onset cerebrovascular disorders during normocapnia and during hyperventilatory hypocapnia. Hypocapnia led to a reduction of both blood flow and blood velocity in the territory of the middle cerebral artery. However, correlation was poor in most cases with respect: 1) to hemispheric blood flow and flow velocity over the middle cerebral artery (BFV), 2) cerebral blood flow (CBF) over the middle cerebral artery (MCA) and BFV and 3) percentage changes of CBF over the MCA and BFV during hypocapnia. In normals correlation usually was better than in patients with cerebrovascular disorders. It was concluded that measurement of BFV over the MCA using transcranial Doppler sonography does not reflect either cerebral tissue perfusion or changes of tissue perfusion induced by alteration of CO2-content in the arterial blood. PMID- 1902915 TI - Residual sensorimotor functions in a patient after right-sided hemispherectomy. AB - Sensorimotor functions were examined in a patient with left-sided infantile hemiparesis who underwent hemispherectomy (HS) on the right side at age 18 for intractable epilepsy. Pathological examination of the removed hemisphere showed a porencephalic cyst of the temporal lobe and of the frontoparietal operculum. On examination, the patient had hemianopia to the left and sensorimotor deficits only of the distal limbs contralateral to the HS. She walked with a barely perceptible limp. Axial and proximal movements were quasi normal, so that the patient could fully elevate both arms, flex and extend the forearm with nearly normal power and execute small, isolated precision movements of the arm around the shoulder joint. This astonishing proximal motor repertoire was mimicked on the somatosensory side where cutaneous sensation and kinesthesia were normal above the elbow and knee and contrasted the pronounced distal sensorimotor dysfunctions. Movement analysis by means of an optoelectronic two-camera position analysis system (Selspot II) showed normal flexion-extension synergies during gait, but abnormal synergic coupling between the shoulder and elbow joint during reaching and prehension. Distal movements were still possible but could only be performed as rigidly coupled movement synergies, such as closing and opening of the fist along with arm adduction/flexion or abduction/extension. She could engage these synergies for grasping and holding large objects. The performance of individual, fractionated finger movements was impossible. Involuntary mirror movements were elicited in both the affected and the normal arm, but with distinctly different phase relationships, indicating that different circuitries contribute to their generation. The case study reveals the existence of a bilaterally organized sensorimotor system that has the potential to provide quasi normal performance of the axial-proximal body parts on both sides. This raises the question why this potential cannot be better used in cases with only partial unilateral brain damage and persistent hemiplegia. PMID- 1902917 TI - The regional distribution of sulphonylurea binding sites in rat brain. AB - Sulphonylureas such as glibenclamide, which are used in the treatment of Type-2 diabetes, are inhibitors of ATP-sensitive potassium channels. These channels link cellular metabolism to membrane electrical activity and it is likely that they are closely associated with glibenclamide binding sites. Quantitative autoradiography was used to localize high-affinity [3H]glibenclamide binding sites in coronal sections of rat brain. The relative density of binding sites was found to correlate well with the relative capacity of sites determined in homogenate assays. There was no evidence of any variation of affinity between brain regions. The highest levels of binding were found in the substantia nigra with high levels in the globus pallidus, cerebral cortex, hippocampus and caudate putamen, intermediate levels in the cerebellum, and low levels in the hypothalamus and pons. The density of [3H]glibenclamide binding sites was low in glucose-responsive brain regions, known to contain ATP-sensitive potassium channels that are inhibited by sulphonylureas. However, higher densities were associated with brain regions (often limbic structures) active during temporal lobe epilepsy. In at least two of these structures, the CA3 region of the hippocampus and the substantia nigra, it is probable that these sites are coupled to ATP-sensitive potassium channels. These results are discussed with reference to the reported actions of ATP-sensitive potassium channels on CNS function. PMID- 1902916 TI - The effect of chronic L-dopa treatment on the recovery of motor function in 6 hydroxydopamine-lesioned rats receiving ventral mesencephalic grafts. AB - The effect of treatment for 5 weeks with L-DOPA (200 mg/kg/24 h) plus carbidopa (25 mg/kg/24 h) on the behavioral recovery produced by rat fetal ventral mesencephalon grafts implanted into the striatum of 6-hydroxydopamine-lesioned rats was assessed. Animals with unilateral 6-hydroxydopamine lesions of the nigrostriatal pathway and a sham graft (Group A) showed persistent high rates of rotation in response to the administration of apomorphine (0.5 mg/kg, s.c.) (contralateral rotation) or (+)-amphetamine (5 mg/kg, i.p.) (ipsilateral rotation). Treatment of sham-grafted animals with L-DOPA plus carbidopa had no effect on the rate of rotation to apomorphine or (+)-amphetamine (Group B). The proportion of animals showing marked stereotypy following apomorphine administration was greater in sham-grafted animals receiving L-DOPA and carbidopa than in sham-grafted animals alone. Animals receiving unilateral 6 hydroxydopamine lesions followed by a fetal graft (Group C) showed a reduction in apomorphine-induced contralateral rotation and a complete reversal of (+) amphetamine-induced ipsilateral rotation when assessed 6 weeks later. The reductions in apomorphine- and (+)-amphetamine-induced rotational behaviour produced by the fetal graft in animals with a 6-hydroxydopamine lesion were not altered by treatment with L-DOPA plus carbidopa (Group D). The proportion of animals showing marked apomorphine-induced stereotypy did not change significantly in either group over time. In rats with a unilateral 6 hydroxydopamine lesion receiving fetal dopamine grafts, treatment with high doses of L-DOPA and carbidopa for 5 weeks does not have a detrimental effect on the functional activity of the grafts as assessed by reduction of apomorphine- and (+)-amphetamine-induced motor asymmetry. The continuation of L-DOPA therapy may not adversely affect fetal graft survival and growth in patients with Parkinson's disease. PMID- 1902918 TI - Miosis and internal ophthalmoplegia as a manifestation of partial seizures. AB - We present a patient whose only physical manifestation of a partial sensory seizure was bilateral pupillary constriction and internal ophthalmoplegia. The onset and offset of each attack corresponded distinctly with an electroencephalographic discharge of the left temporo-occipital region. We propose involvement of a cortical pupillary constrictive center in the temporal occipital area. PMID- 1902919 TI - Spinal cord schistosomiasis: a pediatric case mimicking intrinsic cord neoplasm. AB - We present the clinical, myelographic, MRI, and histologic data on a 7-year-old girl with confirmed Schistosoma mansoni infection of the spinal cord. MRI of the granulomatous spinal lesion revealed extensive enlargement of the cord in the T11 12 area, with some intramedullary swelling extending to T-5 through T-7. The clinical manifestations of spinal schistosomiasis can be diverse, and there should be a high index of suspicion for all patients from endemic areas. PMID- 1902920 TI - Acetazolamide therapy. PMID- 1902921 TI - Calcium-dependent release of accumulated glutamate from synaptic vesicles within permeabilized nerve terminals. AB - We have studied glutamate release from synaptic vesicles in permeabilized synaptosomes, which were preloaded with [3H]glutamate in an ATP-dependent manner. The release was found to be calcium-dependent and to require a heat-labile cytosolic macromolecule factor for maximum activity. Maximal release occurred at 5 microM free Ca2+ and within 5 min. Of the other divalent cations tested, only barium stimulated release of vesicular glutamate. The release was inhibited by N ethylmaleimide. These results are characteristic of exocytotic release of monoamines and peptides observed in endocrine systems, and constitute direct evidence for the notion that calcium-dependent release of glutamate originates from the vesicular pool. PMID- 1902923 TI - Controlled noxious chemical stimulation: responses of rat trigeminal brainstem neurones to CO2 pulses applied to the nasal mucosa. AB - The nasal mucosa of halothane-anesthetized rats was stimulated with defined CO2 pulses. Recordings were performed from single trigeminal brainstem neurons to characterize their responses to this controlled chemical irritation. All cells examined with this stimulus displayed graded discharges to increasing concentrations of CO2. Enhanced responses were obtained in a group of neurons when the duration of the interstimulus interval was increased. The application of chemical irritants, notably mustard oil or acetic acid induced vigorous ongoing discharges in all cells tested. The CO2 stimulation method described here thus provides an ideal model for the quantitative physiological and pharmacological examination of chemically induced nociception. PMID- 1902922 TI - Characterisation of methylphenidate and nomifensine induced dopamine release in rat striatum using in vivo brain microdialysis. AB - The in vivo effects of methylphenidate (50 mg/kg) and nomifensine (20 mg/kg) on dopamine release and metabolism in the rat striatum were studied using brain microdialysis. Dialysate catecholamine content was measured by high pressure liquid chromatography with electrochemical detection. Both compounds increased the dialysate content of dopamine (430% and 320% of basal efflux, respectively). Release was inhibited by reducing extracellular calcium levels and by infusion of tetrodotoxin (2 microM) via the dialysis probe (calcium free-39 +/- 18% of control, methylphenidate; 40 +/- 17% of control, nomifensine; tetrodotoxin-35 +/- 19% of control, methylphenidate; 40 +/- 14% of control, nomifensine) and also by prior depletion of dopamine storage pools using reserpine (5 mg/kg) (15 +/- 12% of control, methylphenidate; 19 +/- 9% of control, nomifensine). Dialysate levels of dihydroxyphenylacetic acid were not altered by either drug whereas homovanillic acid levels increased. These data suggest that both drugs increase dialysate dopamine content by facilitating Ca2(+)-dependent vesicular release most probably by inhibition of dopamine reuptake. PMID- 1902924 TI - Influence of controlled hypotension by adenosine triphosphate or nitroglycerin on the neuromuscular blocking effect of atracurium in dogs. AB - The neuromuscular blocking effect of atracurium under the influence of controlled hypotension by adenosine triphosphate (ATP) or nitroglycerin (NTG) was studied in mongrel dogs under halothane anesthesia. Under hypotensive state (60 +/- 5 mmHg) elicited by ATP (0.5 mg/kg/min) or NTG (1 microgram/kg/min), the neuromuscular blockade produced by atracurium (30 micrograms/kg, i.v.) was significantly potentiated and prolonged. The maximal depression of twitch contraction of the gastrocnemius-soleus muscle increased from 10 +/- 3% to 36 +/- 10% (ATP group) and 56.0 +/- 2.4% (NTG group), while the duration of neuromuscular blockade was prolonged from 663 +/- 96 s to 1060 +/- 277 s (ATP group), and 1375 +/- 441 s (NTG group). The potentiation and prolongation of neuromuscular blockade by atracurium was still apparent upon reversal of the hypotensive effect of ATP, but not of NTG, by dopamine infusion. We suggest that ATP may prolong and augment the effect of atracurium by reducing the presynaptic release of acetylcholine at the neuromuscular junction. PMID- 1902925 TI - Decision support systems for product line management. PMID- 1902926 TI - Rhesus immunization: new perspectives in maternal-fetal medicine. PMID- 1902927 TI - Differential diagnosis and causes of nonimmunological hydrops fetalis: a review. AB - Twenty-five babies with nonimmune hydrops fetalis were born during a 20-year period from 1967 to 1987 (1/1475). Sixteen were live-born, only three survived. Although hydrops can be caused by a myriad of diseases, a simple classification is proposed in order to allow efficient diagnostic workup. For the majority of cases of nonimmune hydrops no cause can be found. Vascular causes are most frequent, followed by chromosomal, placental, hematological, infectious, and a miscellaneous group of causes. Of the cases reviewed fetal causes dominate in 95 per cent of cases. Maternal causes are relatively rare and consist mainly of infections and diabetes. In order to reduce the high mortality rate of 98 per cent one should aim at early diagnosis of hydrops fetalis, extensive investigation of both the fetus and the mother, and referral to a center for intensive perinatal care. PMID- 1902928 TI - [Incidence of hepatitis C virus antibodies in blood donors, high risk patient groups, liver diseases and health professionals. Multicenter study of the ABBOT ELISA method, comparison with the ORTHO test]. AB - Serum samples from 1185 individuals (blood donors, health care workers, patients on haemodialysis or from other high risk groups or with non-A, non-B [NANB] hepatitis and other liver diseases) were examined for antibody to a recombinant antigen of hepatitis c virus (anti-HCV). A new ABBOTT HCV EIA system was used and a parallel study with ORTHO HCV ELISA was also done for 380 samples to compare the two anti-HCV tests. A confirmatory neutralizing ABBOTT ELISA probe was also performed in 45 cases. Anti-HCV seropositivity was found in 1.60% of accepted healthy blood donors, while among subjects excluded from donation for elevated aminotransferase the rate was 8.95%. In patients on haemodialysis 47.15% anti-HCV prevalence was found, in other high risk group subjects 32.5%. Patients with acute post-transfusion (PT) NANB hepatitis showed 40% prevalence, this rate in chronic PT-NANB was 77.8%. The two ELISA tests revealed 95% agreement in the parallel determinations. Serial dilution studies of anti-HCV positive sera showed that ABBOTT test was of superior sensitivity. The results of the confirmatory test suggest that reactive (positive) samples of low optical density near to the cut-off value require a confirmation with the neutralization test. In conclusion HCV infection in Hungary seems to be a common aetiologic factor in PT-NANB hepatitis and the screening of blood donors for anti-HCV may be useful. However, because of financial difficulties, cost/benefit calculations are recommended before the introduction of this preventive measure. PMID- 1902929 TI - Changing patterns of epiglottitis in children. AB - With an increased awareness of appropriate management of childhood epiglottitis, overall morbidity and mortality has decreased. However, some trends have developed over the past several years that are variations on the classic picture. In a series of 42 patients seen from 1977 to 1986, epiglottitis has occurred in a progressively younger population. Thirty-six percent of our patients were found to be less than 2 years old, and 51% were less than 3 years old. Also, the causative organism, Haemophilus influenzae, has been found to be increasingly ampicillin-resistant. The incidence, presentation, management, and outcome of the patients are reviewed, and compared to similar data from other series in the literature. PMID- 1902930 TI - Diagnostic efficacy of in vitro methods vs. skin testing in patients with inhalant allergies. AB - The purpose of our study was to investigate the diagnostic efficacy of two selected methods of in vitro allergy testing. Specifically, the PRIST/modified RAST I125 isotope systems and the Quantizyme/modified EAST alkaline phosphatase method were compared. The time, expense, convenience, and diagnostic efficacy of the two procedures are discussed. Special attention is given to the practicality of each method for the practicing physician. PMID- 1902931 TI - Protective effect of electrical stimulation in the deafened guinea pig cochlea. AB - The effect of chronic intrascalar electrical stimulation on the spiral ganglion cell survival of the ototoxically deafened guinea pig was investigated. Immediately after ototoxic drug administration, unilateral sinusoidal (1 kHz) charge-balanced electrical stimulation on a 50% duty cycle was administered for 2 hours per day, 5 days per week, at intensities from 0 (control) to 400 microAmp via an implanted scala tympani electrode. The relationship of electrically evoked middle latency response (EMLR) to stimulation protocol and cell survival was studied. At 9 weeks post-drug treatment, the animals were killed and temporal bones were prepared for morphometric analysis of spiral ganglion cell density. The subjects showed essentially complete elimination of outer hair sensory cells, with minimal remaining inner hair cells confined to apical turns. Variable loss of spiral ganglion cell populations was observed, which related to electrical stimulation. In animals that received daily unilaterally electrical stimulation, statistically significant increases in survival of spiral ganglion cells were observed in the stimulated ear, compared to the nonstimulated ear-particularly in basal cochlear regions near the electrode. Spiral ganglion cell density was a function of stimulation current intensity level. Moreover, the slope of the amplitude input/output (I/O) function of the EMLR was found to be dependent on stimulating current level. The effect of stimulation on induced survival may be dependent on a number of mechanisms, including metabolic effects of direct activation of "deafferented" spiral ganglion cells. These data support the suggestion that implantation may provide optimal benefits when performed shortly after deafness. PMID- 1902933 TI - Is melanoma changing? AB - Nine hundred ninety-five cases of melanoma of the head and neck were divided into two groups so that certain comparisons could be made concerning the behavior of melanoma over a 55-year period. One hundred twelve melanomas of the ocular system were excluded from this review. The first group consisted of 660 melanomas seen during a period from 1932 to 1972. The second group consisted of 223 melanomas seen during a period from 1973 to 1987. Thirteen parameters, including sex, age, distribution, pre-existing mole, amelanotic melanoma, delay in diagnosis, classification, levels, local recurrence, regional metastasis, systemic metastasis, morbidity, and survival, were studied to assess the behavior and the variations. There is no question that the most important aspect of the favorable changes that have occurred are because of earlier diagnosis and better management by a larger group of well-trained specialists. There are some subtler changes that could possibly indicate biologic alterations, but this requires more time and study to substantiate. PMID- 1902932 TI - Labyrinthitis ossificans: histopathologic consideration for cochlear implantation. AB - Labyrinthitis ossificans may be a hindrance to cochlear implantation by making electrode insertion difficult. We performed a histopathologic study of 24 temporal bones with labyrinthitis ossificans from multiple causes. The organ of Corti was graphically reconstructed and the degree of obstruction was estimated for each millimeter of the cochlea. Correlations were calculated between the degree of new bone formation and the cause, patient's age and sex, and time from the original temporal bone insult. Our results demonstrate that complete cochlear ossification is rare. The scala tympani in the basal turn of the cochlea is the most frequent area of ossification, regardless of the cause of the labyrinthitis ossificans. Meningogenic labyrinthitis, usually a childhood disease, was associated with the greatest amount of ossification. When ossification resulted from tympanogenic labyrinthitis, the scala tympani was completely ossified near the round window niche in all temporal bones. Neo-ossification of the basal turn associated with otosclerosis was limited to the proximal 6 mm of the scala tympani in all cases. Three temporal bones had a patent round window niche and basal turn, but significant apical and middle-turn ossification. Peripheral sensorineural elements were severely degenerated in the region of the ossification in all specimens, and spiral ganglion cell counts were decreased. PMID- 1902934 TI - Evaluation, treatment, and follow-up results of post polio patients with dysphagia. AB - Twenty consecutive patients were evaluated for reports of dysphagia from post polio clinics. Only half the patients reported a history of swallowing problems at the time of their acute poliomyelitis. Each patient received a videofluorographic evaluation of the oral and pharyngeal phases of swallowing, and then was provided with recommendations to improve swallowing skills. A follow up questionnaire was sent to all patients. The respondents had an average interval of 12 months since the initial evaluation. Of the 18 patients responding to the questionnaire, 14 (77%) reported regular use of the swallowing suggestions. Comparison of pre-evaluation results to followup of the 18 respondents yielded a statistically significant decline in the frequency of choking (p = 0.0156) and food sticking in the throat (p = 0.0195). We conclude that a dysphagia program can result in significant improvement of the swallowing symptoms reported with the post-polio population. PMID- 1902935 TI - Videoendoscopic evaluation of patients with dysphagia: an adjunct to the modified barium swallow. AB - The modified barium swallow is currently the most comprehensive, widely available, and easily interpreted technique for the evaluation of patients with dysphagia by the head and neck surgeon. However, it requires the facilities, personnel, and use of a radiology suite, a trained speech pathologist, and exposure of the patient to radiation. It would therefore be helpful to have an adjunctive, physician based, nonradiographic method of examination that could provide information similar to and possibly even more complete than that supplied by the modified barium swallow. Such an adjunctive method could help otolaryngologist-head and neck surgeons confronted by a new patient with swallowing difficulties to orient themselves to the nature and severity of the problem while waiting for the modified barium swallow to be scheduled, performed, and reviewed. It could also be a helpful tool for management of patients with cancer of the head and neck, whose swallowing function may change rapidly in the early postoperative period. In such cases, intervals between modified barium swallow examinations (dictated by concern over radiation exposure) may be too far apart to allow up-to-the-minute decisions on case management. Finally, some patients who may be too ill to travel to the radiology suite might benefit from a bedside procedure that would yield information about swallowing function similar to that provided by the modified barium swallow. Videoendoscopic evaluation of dysphagia (VEED) is a protocol I developed and have used regularly since 1984. Experience with this method of dysphagia evaluation has shown that it answers the needs outlined above. Its usefulness also goes beyond that of the modified barium swallow by providing a more detailed understanding of the component anatomic and functional deficits that comprise a given patient's swallowing problem, information about upper aerodigestive tract sensory deficits, and a means for visual feedback training of pharyngeal and laryngeal musculature. The protocol is reviewed here. Case reports illustrating the clinical usefulness of VEED as an adjunct to the modified barium swallow are also presented, and the relative strengths and weaknesses of VEED and the modified barium swallow are compared. PMID- 1902936 TI - Growth and histopathology of human head and neck squamous cell carcinoma implanted intraorally in nude mice. AB - A human squamous cell carcinoma (SCC) from the floor of the mouth (FOM) was implanted by a needle aspiration technique in the FOM site of athymic nude mice. Mice were killed at 3-week intervals, and the oral cavity, mandible, and neck were sectioned and examined histologically. Tumor growth was observed in 65% of the animals, with histologic features consistent with the engrafted human invasive SCC. These features included invasion of connective tissue in 92%, invasion of muscle in 77%, invasion and destruction of bone in 54%, and vascular invasion in 15% of the mice. In contrast, FOM tumor implanted subcutaneously on back sites of nude mice was totally encapsulated by fibrous connective tissue with evidence of capsular invasion. SCC from other head and neck sites showed similar locally invasive growth after intraoral implantation in nude mice. The results demonstrate the invasive characteristics of human head and neck SCC grown in the homologous oral cavity site in nude mice and support the nude mouse as a biologically relevant in vivo model in the investigation of the biologic characteristics and therapy of head and neck carcinoma. PMID- 1902938 TI - Laryngeal involvement in scleromyxedema: a case report. PMID- 1902937 TI - Transantral sphenoethmoidectomy: a procedure for the 1990s? AB - Currently, among otolaryngologists, much attention is focused on the surgical management of paranasal sinus disease. However, transantral sphenoethmoidectomy is rarely mentioned in the literature of the past several decades. We reviewed a consecutive series of 98 patients over a 12-year period who underwent transantral sphenoethmoidectomy in the treatment of severe chronic hyperplastic pansinusitis. The major and minor complications encountered are tabulated, as are the clinical outcomes. A description of the operative technique is followed by a discussion of the indications for this approach. We believe transantral sphenoethmoidectomy has a useful place in modern paranasal sinus surgery. PMID- 1902939 TI - Cricoarytenoid arthritis in children. PMID- 1902940 TI - Traumatic Eagle's syndrome. PMID- 1902941 TI - Carotid artery laceration secondary to thyroid cartilage fracture: an unusual complication of blunt neck trauma. PMID- 1902942 TI - Spontaneous CSF rhinorrhea: an unusual presentation of a pituitary adenoma. PMID- 1902943 TI - Invasive Chrysosporium infection of the nose and paranasal sinuses in an immunocompromised host. AB - Aggressive fungal rhinosinusitis with Chrysosporium sp. occurred in a patient with acute lymphocytic leukemia. The infecting organism is an exceedingly rare human pathogen. Usually, human chrysosporial infections are mild and unmarked by symptoms. Most case reports appear in the pathology literature and describe the incidental finding of adiaspores in the pulmonary parenchyma at autopsy. Clinical disease from active growth of chrysosporial mycelia in human tissues has been noted on a porcine aortic valve prosthesis and in a tibial abscess. Hyphal elements were not recovered from any other body parts of these patients. Histopathologic and microbiologic studies permitted the identification of this rarely encountered organism. Our patient experienced systemic spread of Chrysosporium organisms. Treatment of this pathogen is the same as for other opportunistic fungal infections. PMID- 1902944 TI - Facial nerve bifurcation within the internal auditory canal. PMID- 1902945 TI - Hereditary angioedema: case report and review of management. PMID- 1902947 TI - Protection of sigmoid sinus during neurotologic surgery. PMID- 1902946 TI - Tympanoplasty: to stage or not to stage. AB - No unanimity of opinion exists in regard to staged operations in tympanoplasty. The controversy centers around the degree to which one should attempt to obtain hearing improvement in badly diseased ears. The major factor is the extent of the mucous membrane disease. We review the history of staging, the mucous membrane indications for staging, and the variations involved in canal-wall-down (CWD) procedures. The opinions of nineteen other otologists also are presented, nine of whom do not regularly or ever stage tympanoplasty. PMID- 1902948 TI - A new instrument for the simplification of tracheoesophageal puncture. PMID- 1902949 TI - Human transcription factor IIIC binds to its cognate promoter sequences in a metal coordinated fashion. AB - Transcription factor IIIC from human cells (hTFIIIC) contains a 55 kDa polypeptide which specifically binds to the promoter of the VAI and 5S gene. This interaction can be abolished by depleting divalent metal cations from the free protein through chelation with EDTA. Prior association of the protein with its DNA-binding sequence renders the complex refractory to chelation by EDTA. Specific binding of hTFIIIC to its cognate promoter sequences--shown by electrophoretic mobility shift and DNase I protection assays--can be restored by the addition of zinc ions. In contrast to the binding of hTFIIIA to the 5S gene, which was monitored in parallel and which exclusively requires Zn2+, the binding of hTFIIIC to the VAI and 5S gene can also be reconstituted--albeit with a lower efficiency--by the transition metals Co2+, Fe2+ and Mn2+ but not by Ni2+ or Cu2+. These results show that hTFIIIC binds to its promoter sequences in a metal coordinated fashion which differs from that observed for the binding of hTFIIIA to the 5S gene. PMID- 1902950 TI - Nucleotide sequence of murine purine nucleoside phosphorylase cDNA. PMID- 1902951 TI - Dinucleotide repeat polymorphism at the human MHC class I CD8 alpha-chain (Leu 2/T8) gene. PMID- 1902952 TI - [Testosterone-inhibin interaction in male sterility]. AB - The purpose of investigation was to define the role of hormones, circulating in the peripheral blood and contained in the seminal fluid of an ejaculate, in the pathogenesis of sterility. Men under 40 with a secretory type of sterility were investigated. A decrease in testosterone concentration with a high level of estradiol was observed in peripheral blood. Blood inhibin activity was low in healthy persons and in patients (though higher in the latter). LH and prolactin levels were raised in the absence of changes in FSH and cortisol concentrations. The level of testosterone in the seminal plasma was much lower than in peripheral blood whereas inhibin activity was higher in all examinees. Blood concentration of testosterone in healthy subjects and sterile patients was shown to have a positive correlation with the concentration of spermatozoa and their mobility. Testosterone concentration in the seminal plasma was reflected, to a lesser degree, in spermograms than in peripheral blood. The activity of circulating and seminal inhibin showed reverse correlation with the concentration of spermatozoa in healthy subjects; such a correlation in patients was observed only with blood inhibin. In the activity of spermatozoons negative correlation was observed in healthy subjects only. Disorder of the above correlation was revealed against a background of the high activity of inhibin that could determine sterility. PMID- 1902953 TI - [Effect of sex steroids on the activity of cardiac lysosomal enzymes]. AB - Experiments on rats were staged to investigate the activity of lysosomal cardiac enzymes (beta-galactosidase, beta-glucosidase, acid phosphatase) against a varied endogenous background of sex steroids (in male and female animals and in females at various stages of the estrual cycle) and a possibility of direct influence of steroids on lysosomes. The investigation has shown sex differences in the activity of lysosomal cardiac enzymes of rats: total activity of beta galactosidase, beta-glucosidase and acid phosphatase in the heart of male rats was higher than that of female rats. Correlation between the activity of lysosomal cardiac enzymes of female rats and stages of the estrual cycle was noted. Sex hormones at high (nonphysiological) concentrations could produce a direct effect on rat cardiac lysosomes, estradiol as distinct from testosterone, causing stabilization of lysosomal membranes. PMID- 1902954 TI - Purification of merozoites of Theileria sergenti from infected bovine erythrocytes. AB - A simple and rapid method for purifying merozoites of Theileria sergenti from infected bovine erythrocytes was developed. Infected erythrocytes were lysed by the use of a cytolytic toxin produced by Aeromonas hydrophila and the lysate was subjected to ultracentrifugation in a Percoll discontinuous density gradient. Pure and morphologically intact merozoites free of erythrocyte membrane were recovered from a band formed at the interface of 40% and 60% (by vol.) Percoll solutions. In this merozoite fraction, contamination of erythrocyte membrane proteins was not detected as examined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. PMID- 1902956 TI - The chemiluminescence of amides and monoacyl hydrazides based on firefly dehydroluciferin. AB - Monoacyl hydrazides based on 5-methyldehydroluciferin and simpler analogs have been synthesized; they proved to be chemiluminescent on treatment with a strong base in DMSO in the presence of oxygen. The light emitters in these cases appear to be the corresponding carboxylate ions; a pathway involving an oxidative decarboxylation was eliminated as a possibility by consideration of the fluorescence wavelengths of the corresponding oxyluciferins. A reaction mechanism for the luminescence involving the possible intermediacy of an azadioxetane is proposed. The corresponding amides were also synthesized; they proved to be equally chemiluminescent to the hydrazides in the dehydroluciferin series. PMID- 1902955 TI - The infection characteristics of a South African isolate of Schistosoma mansoni: a comparison with a Puerto Rican isolate in BALB/c mice and Mastomys coucha. AB - The infection characteristics of a South African (RSA) laboratory isolate of Schistosoma mansoni were compared with those of a widely studied Puerto Rican (PR) isolate in BALB/c mice and Mastomys coucha over the period of 5-12 weeks after infection. The infectivity, maturation and, in particular, the fecundity of the two schistosomes were found to differ markedly. Tissue egg-accumulation rates of the RSA strain were substantially lower than those of the PR strain. Although the maturation of both parasite strains was somewhat delayed in M. coucha, the characteristics of each was essentially consistent in both rodent hosts. Notwithstanding the possible influence of prolonged laboratory passage on the behaviour of schistosome isolates, the results of the present study are nevertheless considered to support the idea that parasite strain differences may, to some extent, account for regional variations in the morbidity of intestinal schistosomiasis. The need to be cognizant of the characteristics of individual host-parasite combinations when comparing different schistosome species and strains, particularly with respect to both their abilities to elicit immunopathology and induce concomitant immunity and their susceptibilities to chemotherapy, is highlighted. PMID- 1902958 TI - Modification of tumor development in the pancreas. PMID- 1902957 TI - Percutaneous feeding tube method for use in children. AB - Surgical gastrostomy has been a widely accepted method for introducing a percutaneous feeding tube for many years. However, complications are frequent, and many children who need them are not good surgical candidates. This study examines imaging guided percutaneous placement of feeding gastrostomy catheters as a safe and effective alternative to surgery. PMID- 1902959 TI - Mammary tumorigenesis. PMID- 1902961 TI - [7th Annual Meeting of Applied Research in Chagas Disease, Uberaba, February 23 25, 1991. Program and abstracts]. PMID- 1902960 TI - Modification of multistage skin carcinogenesis in mice. AB - The multistage model of mouse skin tumorigenesis has been extremely useful for studying various factors that modify the carcinogenic process. Using this model system one can specifically study the effects of potential modifiers on both the initiation and the promotion stages independently. Studies have been performed on many exogenous compounds that have the capacity to inhibit (and in some cases enhance) the initiation phase by either: (i) alteration of the metabolism of the carcinogen (decreased activation and/or increased detoxification); (ii) scavenging of active molecular species of carcinogens to prevent their reaching critical target sites in the cells; (iii) competitive inhibition; or (iv) modulation of epidermal DNA synthesis. In addition, there have been a number of studies on compounds that either inhibit (or again in some cases enhance) promotion of skin carcinogenesis by (i) altering the state of differentiation; (ii) inhibiting the promoter-induced cellular proliferation; (iii) preventing gene activation by promoters; or (iv) scavenging free radicals and reactive oxygen species. Recent studies have also begun to unravel the nature of the tumor progression process of skin carcinogenesis. Many factors can modulate tumor progression including: (i) subsequent exposure to genotoxic agents; (ii) dose, duration and frequency of promoter treatment, (iii) chemical nature of the promoting agent. The multistage model of skin tumorigenesis has also begun to provide insight into the role of specific dietary, immunologic, and genetic factors involved in chemical carcinogenesis. It is believed that further study of all of these factors will greatly enhance our understanding of the process of chemical carcinogenesis in epithelial tissues in general as well as the process of skin carcinogenesis specifically. Finally, a greater understanding of those factors modifying skin tumorigenesis in mice will provide valuable information on the further development of early detection and prevention strategies for chemical carcinogenesis in humans. PMID- 1902962 TI - Paradoxic elevation in serum GH by hypothalamic releasing hormones predicts GH response to acute SMS 201-995 administration. AB - Acromegalic patients do not respond with the same degree of growth hormone (GH) inhibition to long-term therapy with the somatostatin analogue SMS 201-995. In order to find a parameter predictive of the effectiveness of the drug, we studied in twelve patients with active acromegaly the relationship between paradoxical GH response to gonadotropin- and thyrotropin-releasing hormone (GnRH and TRH) and GH inhibition after a single standard dose (100 micrograms) of SMS 201-995. Four hours after the subcutaneous injection of the analogue, only those patients who responded to the releasing hormones demonstrated a persistent inhibition of somatotropic cell function. SMS 201-995 appears an effective means for suppressing the elevated GH levels in active acromegaly. Its activity may be more pronounced and its use more beneficial in those patients who react paradoxically to GnRH and TRH. PMID- 1902963 TI - Role of pulsatile luteinizing hormone releasing-hormone therapy in males with idiopathic hypogonadotropic hypogonadism and delayed puberty. AB - The aim of our work was to review the literature to evaluate the importance of pulsatile LHRH administration therapy in males with idiopathic hypogonadotropic hypogonadism (IHH) and delayed pubertal development. Among the various routes of administration (iv, sc, nasal) we believe that sc administration is better in IHH males whereby a long-term therapy is needed. With regard to the differential diagnosis of pubertal delay, the diagnostic use of LHRH administration for a short-period is still being debated. Biochemical controls show that response to therapy is quick in all of the subjects treated. 30-50% of IHH subjects can obtain adequate sperm production. The appearance of antibodies to LHRH is a rare phenomenon. We can conclude that pulsatile sc therapy is more physiological and better tolerated for a longer time. PMID- 1902964 TI - Contribution of chemical feedback loops to breath-to-breath variability of tidal volume. AB - We tested whether chemical feedback loops contribute to the breath-to-breath correlations seen in respiratory cycle parameters. We have analyzed tidal volume (VT) of seven anesthetized, vagotomized, spontaneously breathing rats and the peaks of the 'integrated' phrenic neurograms (P) of another twelve anesthetized, vagotomized, paralyzed and artificially ventilated rats. Animals were studied while breathing 100% O2, 4% CO2 in O2 and/or room air. Our analysis consisted of fitting a first-order autoregressive (AR1) model to each measured variable in steady-state conditions. We found that: (1) breath-to-breath fluctuations of VT could be described by a first-order autoregressive model in which the fluctuation of VT on each breath from its mean level is correlated with that of the immediately preceding breath; (2) breath-to-breath fluctuations of P were not correlated with those of previous breaths, because successive values of P were uncorrelated random variables. Hypercapnia enhanced correlations in VT (3 rats) but not in P (12 rats). We propose that breath-to-breath correlations of VT in anesthetized, vagotomized and spontaneously breathing rats may reflect the effects of noise in respiratory chemical feedback loops. PMID- 1902965 TI - The influence of venous CO2 on ventilation in garter snakes. AB - Garter snakes were used to study the effects of venous CO2 loading using the skin as an exchanger. The gaseous environment surrounding the snake's body was isolated by placing the body in a plethysmograph with the head out. While the animal breathed room air, the carbon dioxide concentration within the plethysmograph was varied between 0 and 80%. Room air was drawn through a funnel placed over the snake's head, thus collecting the exhaled gases, and this gas was analyzed by O2 and CO2 analyzers. The descending aorta was cannulated to measure blood gases. Expired CO2 flow rose linearly with increasing cutaneous CO2. Ventilation increased 3.5-fold at 80% cutaneous CO2 compared with no cutaneous CO2 load. Neither the mean CO2 concentration in exhaled air nor arterial PCO2 changed when the snake was exposed to high levels of CO2 at the skin. Thus ventilation increased in proportion to the CO2 load, and was not driven by arterial hypercapnia. Bilateral vagotomy eliminated arterial CO2 homeostasis during cutaneous CO2 loading, and ventilation increased with increasing arterial PCO2. Therefore, these snakes respond to extra-arterial elevations in CO2 or to a changing CO2 signal. Furthermore, receptors responsible for the increase in ventilation when venous CO2 is elevated have neurons in the vagus nerves. PMID- 1902966 TI - Time course of temperature effects on arterial acid-base status in Alligator mississippiensis. AB - Temperature effects on extracellular acid-base status in terrestrial poikilotherms are well known. Comparatively less is known concerning the time course of acid-base responses to prolonged changes in temperature. In this study, two questions were addressed: (1) what is the time course of acid-base responses to a temperature change of 5 days duration in Alligator mississippiensis?; and (2) what are the relative contributions of respiratory vs metabolic (strong ion) processes to the acid-base response? The effects of acute (4-6 h) vs chronic (24 120 h) decreases in ambient temperature from 30 to 20 degrees C were determined on arterial blood gases, acid-base status and plasma electrolyte concentrations ([Na+], [K+] and [Cl-]) in 7 awake alligators. In addition, in vivo and in vitro non-bicarbonate buffer values were determined in 6 anesthetized alligators. Acute decreases in temperature decreased PaCO2 (31 to 18 mmHg) and PaO2 (91 to 50 mmHg), increased pH (7.48 to 7.66), but had no significant effect on plasma bicarbonate concentration ([HCO3-]). Chronic exposure to 20 degrees C had no further effect on any variable. dpH/dT ranged between -0.018 and -0.011 U/degrees C, over the duration of the experiment. Temperature did not alter [Na+] or [Cl-] at any time, and had only minor effects on [K+]. In vivo (11.5 +/- 0.7 mEq/L/pH unit) and in vitro (16.1 +/- 0.9 mEq/L/pH unit) buffer values were significantly different, but neither was affected by temperature. Temperature had no effect on the base excess (estimated with either in vitro or in vivo buffer values), nor on estimates of the strong ion difference. We conclude that pH changes during prolonged exposure to decreased temperature occur rapidly and can be explained by changes in PaCO2, CO2 solubility and pK', without major contributions from metabolic or strong ion adjustments. PMID- 1902967 TI - The problem of therapeutic equivalence with paired qualitative data: an example from a clinical trial using haemophiliacs with an inhibitor to factor VIII. AB - The problem of demonstrating the equivalence of two treatments or drugs occurs fairly frequently in medicine, but is quite often misformulated. The common error is to assume equivalence is demonstrated if the usual null hypothesis of no difference is not rejected, which ignores the potential of a substantial beta error. We describe here two procedures for testing equivalence when the data are paired and dichotomous, and provide sample size formulas. We give an example based on a clinical trial of haemophiliacs with inhibitor to Factor VIII. PMID- 1902968 TI - [Postures and abnormal paroxysmal movements during sleep: hypnogenic paroxysmal dystonia or partial epilepsy?]. AB - In recent years, a differentiation has been made between two syndromes that are characterized by brief abnormal paroxysmal movements occurring principally at night: 1, hypnogenic paroxysmal dystonia (HPD), sometimes considered a particular form of dystonia similar to paroxysmal kinesigenic choreoathetosis, and 2, mesiofrontal epilepsy. Whether HPD is a distinct syndrome is not clear. Twenty three patients, 11 men and 12 women, were hospitalized between 1985 and 1989 for examination of this type of abnormal paroxysmal movements (APM) occurring at night. In order to clarify the physiopathology of these abnormal nocturnal movement as focal epilepsy or a particular form of dystonia, we analyzed the personal and familial antecedents of all 23 patients, the polygraphic records during waking and sleep periods, and the results of neuroradiological examinations. Four patients were examined by positron emission tomography (PET) using i8F deoxyglucose. Symptoms first appeared between 3 and 28 years of age (M, 10.1) and developed over 1 to 20 years (M, 10.1). APM clearly occurred more commonly (greater than 90%) during sleep, usually during phases of slow-wave sleep. The sleeping patient opened his eyes and the motor signs then variously associated affective facial expression; axial postural modifications; tonic, dystonic or choreic postural movements of the limbs; pedalling; automatisms; disordered agitation and vocalization. The seizure was abruptly interrupted after 10 to 60 seconds. There was usually no postictal confusion. Thirteen patients clearly had clear epileptic antecedents: in 9, generalized tonic-clonic seizures; in 4, focal epileptic status. During nocturnal polygraphic recording, 6 patients presented a generalized seizure following a period of APM.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1902969 TI - [Role of percutaneous endoscopic gastrostomy in amyotrophic lateral sclerosis]. AB - Percutaneous endoscopic gastrostomy (PEG) is an enteral nutritional assistance technique using a simple device compatible with conventional feeding and thus enabling the patient to be integrated into his or her social and familial surroundings. This inexpensive device is quickly and easily inserted under local anaesthesia. It causes little morbidity and virtually no mortality and has many advantages for patients with amyotrophic lateral sclerosis (ALS). We report the results of PEG in 28 ALS patients with bulbar involvement. Three of these patients developed minor complications during 6 consecutive months of PEG assisted nutrition (2 had periostomial infection, 1 had mild haematemesis). There were no major complications, and mortality directly ascribable to PEG was nil. All patients put on weight or had their weight stabilized, and GEP was well accepted in all cases. PMID- 1902970 TI - [Health economics and nursing in Europe]. PMID- 1902972 TI - [Enteral feeding]. PMID- 1902971 TI - Gonadotropin-releasing hormone analogues inhibit cell proliferation and activate signal transduction pathways in MDA-MB-231 human breast cancer cell line. AB - A novel gonadotropin-releasing hormone (GnRH) agonist (folligen) which stimulates follicular maturation has been developed in our laboratory. The direct effect of folligen and a well-known superactive GnRH analogue, buserelin, on the MDA-MB-231 human breast cancer cell line was investigated. Folligen was found to be slightly more active in inhibiting cell proliferation than buserelin, and significant differences were found in the signal transduction pathways activated by these analogues. These results demonstrate for the first time that tyrosine kinases and/or phospholipid turnover together with protein kinase C activation can be directly involved in the antitumor activity of GnRH analogues. The results also suggest that folligen and buserelin might have a different mechanism of action on this human breast cancer cell line. PMID- 1902973 TI - [Enteral feeding. Principles and techniques, nutritive solutions]. AB - A great number of nutritional solutions can be found owing to the technical progress of enteral nutrition and the diversity of available nutritive solutions. In this paper are described the various materials, their advantages and disadvantages together with the available nutritive solutions. The interests of new methods of gastrostomy by endoscopy and the progress due to the use of nutritive pumps are pointed out. Physicians can now choose the type of feeding adapted to specific nutrients requirements of the patients. They can also vary it in relation to its tolerance and the evolution of nutritional situation. Practice of enteral nutrition needs a very accurate knowledge of material, nutritive solutions and technical uses. They also have to be in agreement with the strict obligations of food hygiene. PMID- 1902974 TI - [Biological and clinical surveillance techniques: problems and complications of enteral feeding]. AB - The present high degree of safety of enteral nutrition is due to improvements in commercial nutritional products and, chiefly, to the respect of well-established rules of administration. Monitoring the equipment consists of making sure, by means of repeated rinsing, that the fine digestive tract prosthesis remains patent. Nutrients are now sterile and easy to use, and their compositions varied and well-balanced. They are very well tolerated in most cases. Monitoring the speed of gastrointestinal (GI) transit is crucial. One must watch for the occurrence of multiple daily stools, due to the speed of administration or to malabsorption, proliferation of exogenous or endogenous pathogens or patient's underlying pathology, and for a gastric fluid residual volume exceeding 150 ml. Regular controls of gastric emptying and of GI prosthesis position prevent the very rare complications that are aspiration pneumonia and unexplained chronic dyspnoea. Possible interference between enteral nutrition and patient's pathology or treatment must be detected and prevented. PMID- 1902975 TI - [Enteral feeding in adults: indications]. AB - In this overview article the author examines successively: (1) the effects expected from enteral nutrition in adults: general and/or local nutritional effects, temporary arrest in progressive intestinal lesions, partial intestinal function replacement; (2) indications in gastrointestinal and non gastrointestinal pathologies and modalities of application to each indication (route of administration, elemental, semi-elemental or polymeric nutrients, incremental or non-incremental calorie intake, necessity or lack of necessity for addition of fibres, value of ambulatory methods); (3) results according to indications: chronic inflammatory intestinal diseases, notably Crohn's disease, short small bowel syndromes, fistulae and stomies, preoperative period in gastrointestinal surgery, support of heavy treatments in non-terminal cancers, hypermetabolic states, notably stress; (4) absolute or relative contraindications of enteral nutrition. PMID- 1902976 TI - [Elemental, semi-elemental, polymeric diets. Choice, indications, rational use]. AB - In this review paper the main properties of elemental, semi-elemental and polymeric diets utilized in enteral nutrition are compared. The theoretical value of elemental diets (they do not require digestion) is upset by their effects on secretion. Semi-elemental diets are not hyperosmolar and are easily absorbed. Polymeric formulas acan be given in almost all indications of enteral nutrition, and in view of the high cost of elemental and semi-elemental diets, the latter should be reserved to elective indications, notably antigenic arrest of the digestive tract and major nitrogen malabsorption. PMID- 1902977 TI - [Enteral feeding in children]. AB - Enteral nutrition in children is indicated in and outside gastrointestinal (GI) diseases. When administered as a continuous flow, it makes it possible to obtain stationary motor, secretory and hormonal functions of the digestive tract and to increase its capacity for digestion and absorption. The introduction of semi elemental diets has made it easier to perform and has enhanced its effectiveness; the preparation of nutritional mixtures requires a structure that is capable of ensuring accuracy and sterility. In some circumstances the conventional nasogastric tube can be replaced by percutaneous gastrostomy. Both monitoring and variations in intakes must take into account the child's nutritional and digestive status in terms of tolerability and efficacy. Enteral nutrition is indicated in such GI diseases as prolonged severe diarrhoea, extensive intestinal resections and inflammatory diseases. Outside GI pathologies it can be used in neonatology, metabolic diseases and intensive care. Enteral nutrition at home enables the nutritional support to be pursued in an optimal psychoaffective environment, and it must be envisaged as soon as medical condition permits. PMID- 1902978 TI - [Prolonged home enteral feeding]. AB - Home enteral nutrition (HEN) is a method that will develop as an alternative to hospitalization. It is indicated mainly in patients who would normally be kept in neurology, ENT, gastroenterology, oncology, paediatrics or geriatrics hospital departments. The technicalities of HEN, such as route, periodicity and modalities of administration and choice of the diet, must be adjusted to the patient's condition and to the foreseeable duration of the procedure. HEN is best organized by a team of hospital specialists who will educate the patient prior to his discharge and follow him up at home in cooperation with the family doctor and district nurse. The extent of financial assistance provided by health insurance organizations is currently under evaluation. PMID- 1902979 TI - Vancomycin-resistant Enterococcus faecalis in a bone-marrow transplant recipient. AB - Since 1988 a number of reports on the emergence of vancomycin-resistant enterococci have been published. We describe an additional case of colonization of and subsequent infection with a vancomycin-resistant Enterococcus faecalis in a bone-marrow transplant recipient, who had never before received vancomycin therapy. The strain was resistant to most antibiotics tested, including low-level resistance to gentamicin and cross-resistance to teicoplanin. It was sensitive to amoxicillin and the lipopeptide antibiotic daptomycin. The origin, the mode of acquisition and the incidence of vancomycin-resistant enterococci are still unknown. The clinical and bacteriological features of the cases reported thus far and the genetic and biochemical basis of vancomycin resistance are discussed. PMID- 1902980 TI - Branhamella catarrhalis septicemia in an immunocompetent adult. AB - A 68-year-old man with otitis media developed signs of disseminated intravasal coagulation (DIC) and shock. Beta-lactamase positive Branhamella catarrhalis grew in all blood cultures and in secretion from the middle ear. The patient was immunocompetent and previously healthy. Severe B. catarrhalis septicemia has so far mainly been described in immunocompromised patients, mostly children, but this report shows that it may occasionally occur in immunocompetent adults. PMID- 1902982 TI - Rationality and cost-effectiveness of diagnosis and treatment of group A streptococci in primary care patients with pharyngitis. AB - Rationality and cost-effectiveness of several strategies for diagnosing and treating sore throat patients were evaluated in primary care. In an empirical material of 2016 patients, 3 different bacteriological methods (traditional culture, slide culture, and latex agglutination test) for the detection of group A beta-hemolytic streptococci (GAS) were compared. Sensitivity analyses were done for several variables, including GAS test performance, testing frequencies, medication rates, and accuracy of clinical evaluation. The amounts of unnecessary medication varied from 19 to 33%, and there were 2.2-8.9% of untreated GAS infections. Strategies based on bacteriology achieved more rational and economic results than treating no one, treating all patients, or using clinical evaluation without bacteriology. The cost-effectiveness of the latex agglutination test depended on the sensitivity of the test. The results were further sensitive to sick leave lengths, cost of antibacterials, and clinical accuracy, but not to GAS test cost. Rapid tests for GAS detection can be recommended, if the sensitivity of the test in the actual working conditions is acceptable. PMID- 1902981 TI - Branhamella catarrhalis as a cause of multiple subpleural abscesses. AB - A pure growth of Branhamella catarrhalis was obtained from subpleural abscesses in a 65-year-old fisherman with a persistent pneumothorax; underlying disorders included lung fibrosis, rheumatoid arthritis, and diabetes mellitus. A thoracotomy revealed extensive thickening of the visceral pleura covering multiple subpleural abscesses. There was a protracted postoperative course despite surgical debridement and antibiotic treatment with a cephalosporin and erythromycin. PMID- 1902983 TI - Bacillus cereus: a significant pathogen in postoperative and post-traumatic wounds on orthopaedic wards. AB - Over a period of 19 months, Bacillus species, most frequently B. cereus, were isolated from postoperative and post-traumatic wounds in 24 patients on orthopaedic wards in a Swedish hospital. Clinical signs of infection were found in all but 3 patients: in 9 patients, mild signs with increased secretion from the wounds; in 10 patients, moderate signs with fever and/or significant local reaction around the wounds; and in 2 patients, severe signs with necrotic infections. Bacillus spp. were isolated from one-fourth of all patients with wound complications following total hip arthroplasty. Their hospitalization was significantly prolonged, compared with a control group (p = 0.0042). Isolates of B. cereus from wounds should not be dismissed as contaminants or as non pathogenic, but must be assessed in the light of the clinical situation. PMID- 1902984 TI - [Tendency to thrombosis following bone marrow transplantation?]. AB - Various thrombosis related parameters of the hemostatic system were evaluated in 11 patients who had had bone marrow transplantation (BMT). At 0, 1, 3 and 6 months after BMT, antithrombin III, heparin cofactor II, protein S (PS), factor VIII:C, von Willebrand factor (vWF:Ag, vWF:RiCof), tissue plasminogen activator (tPA), plasminogen activator inhibitor, thrombin antithrombin III complexes (TAT), d-dimers (DD) and antiphospholipid antibodies (APA) were determined. A statistically significant rise in the levels of vWF was observed after BMT, with a similar trend for tPA. High TAT and/or DD were detected in 10/11 patients and positive APA only in 5/11. Of the other parameters only free PS was permanently low, with normal total PS and C4bBP. These findings suggest persistent thrombin generation peri- and post-BMT. The significantly high vWF and the low free PS could foster a procoagulant state. PMID- 1902985 TI - [Peripheral spontaneous remission of hairy cell leukemia following transfusion associated hepatitis C]. AB - In a 59-year-old patient presenting in October 1981 with pancytopenia, hairy cell leukemia was diagnosed. Splenectomy, followed by treatments with oncovin, lithium, and prednisone were essentially without effect. Up to July 1984 the patient had been regularly transfused with a total of 62 unit. In June 1984 he acquired a transfusion associated hepatitis C which followed a chronic course and resulted in biopsy proven cirrhosis in 1989. The patient became independent of transfusions in July 1984. Repeated blood counts have shown a complete hematologic remission which has now lasted nearly 6 years, whereas focal leukemic infiltrates have persisted in the bone marrow. The patient has tolerated 20 courses of erythropheresis performed because of biopsy proven severe hepatic siderosis without a fall in hemoglobin. It is suggested that the spontaneous long lasting hematologic remission of hairy cell leukemia is due to endogenous interferon produced in the course of chronic hepatitis C. Low serum levels of interferon-alpha and -gamma were detected. PMID- 1902986 TI - Diversity of G proteins in signal transduction. AB - The heterotrimeric guanine nucleotide-binding proteins (G proteins) act as switches that regulate information processing circuits connecting cell surface receptors to a variety of effectors. The G proteins are present in all eukaryotic cells, and they control metabolic, humoral, neural, and developmental functions. More than a hundred different kinds of receptors and many different effectors have been described. The G proteins that coordinate receptor-effector activity are derived from a large gene family. At present, the family is known to contain at least sixteen different genes that encode the alpha subunit of the heterotrimer, four that encode beta subunits, and multiple genes encoding gamma subunits. Specific transient interactions between these components generate the pathways that modulate cellular responses to complex chemical signals. PMID- 1902987 TI - Control of doublesex alternative splicing by transformer and transformer-2 in Drosophila. AB - Sex-specific alternative processing of doublesex (dsx) precursor messenger RNA (pre-mRNA) regulates somatic sexual differentiation in Drosophila melanogaster. Cotransfection analyses in which the dsx gene and the female-specific transformer (tra) and transformer-2 (tra-2) complementary DNAs were expressed in Drosophila Kc cells revealed that female-specific splicing of the dsx transcript was positively regulated by the products of the tra and tra-2 genes. Furthermore, analyses of mutant constructs of dsx showed that a portion of the female-specific exon sequence was required for regulation of dsx pre-messenger RNA splicing. PMID- 1902988 TI - Thoracic myelopathy caused by ossification of the ligamentum flavum. Clinicopathologic study and surgical treatment. AB - The authors reviewed 14 patients with thoracic myelopathy caused by ossification of the ligamentum flavum (OLF). The predominant locality of symptomatic OLF was at the thoracolumbar junction, particularly at T10-11 followed by T11-12. At the level of the thickest OLF in each patient, there were three types of OLF from computed tomography and operative findings: a lateral type in 3 patients, diffuse in 8, and thickened nodular in 3. The diagnosis of OLF-related thoracic spinal canal stenosis was best made by enhanced computed tomography. Histologic study revealed that the developmental mode of OLF was mainly endochondral ossification. Numerous fibrocartilaginous cells were found in the increased and swollen collagen fibers forming the hypertrophic ligamentum flavum (HLF). Ossification extended along the superficial layer of HLF. The size or extension of OLF was relevant to the corresponding diathesis of spinalhyperostosis. Results of laminectomy for OLF were poor because of the high occurrence of complications early on or later deterioration. Therefore, laminoplasty is recommended as a successful procedure for OLF-related thoracic myelopathy, avoiding further local mechanical stress due to tensile force. PMID- 1902991 TI - Private social welfare expenditures, 1972-88. PMID- 1902989 TI - Evaluation of ofloxacin in the treatment of uncomplicated gonorrhea. AB - In an open study, a single oral dose of 400 mg of ofloxacin was administered to 40 men and 20 women who required treatment for uncomplicated gonococcal infection. Thirty-six men and 13 women were evaluable. Ofloxacin eradicated 49 of 49 urethral or endocervical gonococcal infections and 1 of 1 pharyngeal infection. There were 55 pretreatment isolates of Neisseria gonorrhoeae available for antimicrobial susceptibility testing. Twenty-four (43.6%) produced penicillinase. Eighteen (32.7%) isolates that did not produce penicillinase had penicillin MICs greater than or equal to 1.0 micrograms/mL. Twelve (21.8%) isolates had tetracycline MICs greater than or equal to 16 micrograms/mL. The geometric mean minimal inhibitory concentrations (range) for 55 pretreatment N. gonorrhoeae isolates were: ofloxacin, 0.014 (.0078-.03) micrograms/mL; penicillin, 6.30 (.125-128) micrograms/mL; and tetracycline 1.61 (.03-128) micrograms/mL. There were few side effects. Ofloxacin appears to be an effective and safe oral therapy for the treatment of infections caused by N. gonorrhoeae including infections due to penicillin- and tetracycline-resistant strains. PMID- 1902990 TI - Gonorrhea in women prostitutes: clinical data and auxotypes, serovars, plasmid contents of PPNG, and susceptibility profiles. AB - Eighty-nine women prostitutes who underwent clinical and microbiologic examination were found to have gonococcal infection. The median age was 22; 92.1% were from urban areas. Nearly all the women prostitutes refrained from barrier methods (92.1%) and had contact with several partners (91.0%). The most frequent clinical findings were leukorrhea (50.6%), cervicitis (20.2%), and pelvic inflammatory disease (PID) (18.0%). Eighty-one women prostitutes (93.1%) had experienced a previous STD, with Chlamydia trachomatis (34.8%), Trichomonas vaginalis (30.3%), Neisseria gonorrhoeae (29.2%), and Ureaplasma urealyticum (23.6%) as the most frequent microorganisms isolated. Microorganisms associated with N. gonorrhoeae were isolated, mainly T. vaginalis (40.4%), C. trachomatis (31.5%), and Mycoplasma hominis (21.3%). For N. gonorrhoeae, the most frequent auxotypes were prototrophic (67.4%) and Proline (Pro)-dependent (14.6%); 2.2% of the strains were non-auxotypable. Beta-lactamase production was detected in three strains (3.4%) belonging to the auxotype/serovar: Lys/IA, Prototrophic/IB, and Pro/IB. The two former produced the 3.2-MDa "African" plasmid; the latter produced two plasmids (the 4.5-MDa "Asian" and the 24.5-MDa transfer plasmid. PMID- 1902992 TI - A randomized clinical trial of ampicillin, gentamicin and clindamycin versus cefotaxime and clindamycin in children with ruptured appendicitis. AB - This prospective, randomized, double-blind study compares the efficacy, safety and cost-effectiveness of ampicillin, gentamicin and clindamycin (AGC) or cefotaxime and clindamycin (CC) for the treatment of children with complicated appendicitis. Ninety-seven children were randomized. Forty-seven were assigned to the AGC regimen and 50 received CC. Forty-two patients in the AGC group had an appropriate therapeutic outcome, whereas 48 of 50 children who received CC completed the trial successfully (p = NS). There were no differences between the groups with reference to the duration of antibiotic administration, fever, leukocytosis or length of hospitalization. Complications of therapy were uncommon and neither regimen demonstrated a significant advantage from an economic standpoint. We concluded that, in childhood, complicated appendicitis can be treated with either CC or AGC with equal efficacy. PMID- 1902993 TI - The role of plasminogen activator in adhesion prevention. AB - The reduction in peritoneal plasminogen activator activity (believed to be the pathogenic mechanism of adhesion formation) and its replacement with recombinant tissue plasminogen activator (rt-PA) have been investigated in the prevention of initial (primary) and recurrent adhesion production. Other, potentially harmful, effects of intra-abdominal rt-PA application have also been examined. This included effects on wound and colonic healing and hemostasis. The prevention of adhesion formation was studied in primary and recurrent adhesion formation using a rabbit model. Primary adhesions formed in one of 14 occasions (7 per cent) with rt-PA compared with 12 of 15 occasions (80 per cent) with placebo (chi-square equals 15.542, p less than 0.001). Recurrent adhesions formed on two of 27 occasions (7 per cent) with rt-PA compared with 22 of 28 occasions with placebo (79 per cent) and 12 of 12 occasions with control rabbits (100 per cent, chi square equals 40.588, p less than 0.0001). The application of rt-PA to abdominal wounds in the rabbit failed to show any reduction in wound strength at four, seven and ten days. Colonic anastomotic healing was unaltered by rt-PA at three, five and seven days. There was no difference seen in hemorrhagic events between control, placebo or rt-PA rabbits at any stage. The use of rt-PA is an exciting development in the field of adhesion prevention; it is an effective inhibitor of adhesion formation and intra-abdominal administration appears safe in a rabbit model. PMID- 1902994 TI - The yield of barium enema in patients undergoing inguinal hernia repair or abdominal hysterectomy. AB - It is the practice of some gynecologists and general surgeons to preoperatively evaluate the colon with a barium enema (BE) examination to exclude potential intestinal involvement or coexistent disease in patients undergoing pelvic or hernia operations. This practice appears to be based on anecdotal data with few studies specifically evaluating its usefulness. We retrospectively evaluated the records of 190 patients at William Beaumont Army Medical Center during 1986 to 1987 who received a preoperative BE prior to total abdominal hysterectomy (TAH) or inguinal hernia repair (IHR). The tumor registry charts of 59 patients diagnosed with carcinoma of the colon and rectum during the same period were also cross-checked to determine if any were detected during preoperative evaluation for TAH or IHR. BE findings were considered significant if they altered surgical management or asymptomatic carcinoma was detected. Of 86 patients screened before TAH by BE, eight had abnormal findings with subsequent colonoscopy revealing four with adenomatous polyps, one of which required surgical resection. Of 104 patients screened before IHR by BE, 15 had abnormal findings with subsequent colonoscopy revealing five patients with adenomatous polyps and two with adenocarcinoma. Screening preoperative BE had a low yield of clinically significant findings, which was even lower in the subgroup with carcinoma. There was no apparent relationship between findings and age in our study. Our results suggest that the use of routine preoperative BE has a low yield and should be performed only if clinical symptoms or findings suggest a need for this study. PMID- 1902995 TI - Successful treatment of Bacillus cereus infection with ciprofloxacin. AB - Bacillus cereus is rarely a pulmonary pathogen but may cause pneumonia in immunocompromised patients. A patient with bronchiectasis and no recognisable immunodeficiency had this organism isolated during two infective exacerbations, once from respiratory secretions and once by blood culture. Ciprofloxacin treatment was effective on both occasions. PMID- 1902996 TI - Shared idiotypic determinant in mono- and polyclonal anti-phospholipid antibodies with lupus anticoagulant activity. AB - Of 42 purified human myeloma proteins tested, two (IgG3 Her and IgM Mag) were found to possess strong lupus anticoagulant (LA) and anti-cephalin activity, as assessed by a dilute activated partial thromboplastin time (dAPTT) and ELISA test, respectively. For these proteins, we confirmed the observation reported by others that LA activity is present in the antigen-binding (Fab) portion of the immunoglobulin molecule. Rabbit anti-idiotype antibodies against IgG3 Her inhibited the anti-cephalin activity of this protein, suggesting that the anti cephalin activity of IgG3 Her depends on the hypervariable part of the immunoglobulin and thus most probably is a true antigen-antibody reaction. The anti-Her idiotype antibodies were also able to bind to and inhibit the anti cephalin activity of IgM Mag. ELISA binding and inhibition experiments showed that the anti-idiotype antiserum contained at least two sets of anti-idiotypes; one set that recognizes a cross-reactive idiotype shared by IgG3 Her and IgM Mag, and another set that seems to be unique to the immunizing protein IgG3 Her. Both sets of anti-idiotype antibodies also bound weakly to polyclonal (patient) IgG, indicating an idiotypic cross reaction. PMID- 1902997 TI - Comparative evaluation of the pharmacokinetics of three monoclonal factor VIII concentrates. AB - Hemofil M, Monoclate HT, and Monoclate P are high-purity Factor VIII concentrates, obtained from plasma by immunoaffinity chromatography with monoclonal antibodies specific for Factor VIII (Hemofil M) or von Willebrand Factor (Monoclate HT and Monoclate P). The concentrates are subjected to virucidal treatments: a solvent/detergent method (TNBP/Na-cholate) for Hemofil M, heating in the lyophilized state and in solution (pasteurization) for Monoclate HT and Monoclate P, respectively. Since these differences in the manufacturing process might result in different in vivo characteristics of the concentrates, we compared their in vivo behavior in a cross-over, single-dose, pharmacokinetic study performed in 10 non-bleeding patients with severe hemophilia A. The experimental conditions (Factor VIII dose, number and timing of blood sampling, Factor VIII assay methods, calculation of pharmacokinetic parameters) were identical for the three products. The results showed that the clearance, the mean residence time, and the volume of distribution did not differ among the three products. PMID- 1902998 TI - Changes of platelet functions by extracellular sodium ion. AB - Effects of extracellular Na+ on platelet responses were examined. Cytoplasmic pH decreased by stimulation with thrombin, TPA and AA in Na(+)-containing buffer as well as in Na(+)-free buffer. Thrombin-induced aggregation and serotonin release were higher in Na(+)-containing buffer, but TPA- and A23187-induced responses exhibited lower values. Thrombin-stimulated platelet in Na(+)-free buffer started to aggregate by the addition of NaCl. Inhibition of thrombin-induced aggregation by indomethacin was apparently weaker than that by removal of Na+. These results suggest that the changes of platelet responses by removal of Na+ is due to the effect of Na+ ion itself, not by the inhibition of Na+/H+ exchanger, and that Na+ affects on mechanisms other than arachidonic acid mobilization. PMID- 1902999 TI - Identification of oleic acid binding sites in cytolysin A-III from the heteronemertine Cerebratulus lacteus. AB - We previously demonstrated that binding of oleic acid to Cerebratulus lacteus cytolysin A-III results in aggregation of this monomeric protein to a tetramer, concomitant with an increase in hemolytic activity. In the present study, incubation of cytolysin A-III with [14C]-oleic acid in the presence of a water soluble carbodiimide results in covalent incorporation of a maximum of two molecules of the fatty acid into the protein. Labeling is restricted to two large tryptic peptides. Sequence analysis of peptide mixtures derived from the labeled protein reveals that the predominant sites of labeling are Lys-31 and Lys-71; the latter site is part of the C-terminal amphipathic helix previously shown to be important for hemolytic activity while the former lies in the other significant hydrophobic region of this largely hydrophilic protein. PMID- 1903000 TI - Effect of route of exposure and repeated doses on the acute toxicity in mice of the cyanobacterial nicotinic alkaloid anatoxin-a. AB - Anatoxin-a (ANTX-a) is a potent nicotinic cholinergic alkaloid produced by some toxigenic strains of cyanobacteria. We have examined i.p. and oral LD50 values of two ANTX-a producing Anabaena sp. and synthetic (+)-ANTX-a in outbred Swiss Webster mice. All three appeared equivalent by i.p. injection, but Anabaena flos aquae NRC-44-1 was approximately twice as potent orally as the other two. Additionally, we were unable to demonstrate development of any biologically significant tolerance to acute ANTX-a exposure using two different repeated dose regimens. PMID- 1903001 TI - The uptake of the cyanobacterial hepatotoxin microcystin by isolated rat hepatocytes. AB - Microcystin-YM a cyclic heptapeptide hepatotoxin isolated from the cyanobacterium Microcystis aeruginosa was radiolabeled with 125I, and used to investigate the uptake of the toxin by freshly isolated rat hepatocytes. The uptake was temperature dependent with apparent activation energy of 18 kcal/mole (77 kJ/mole) for the initial rate of uptake. Uptake of non-toxic (10-20 nM) doses of microcystin by hepatocytes continued with time, the intracellular to extracellular distribution ratio for the toxin was 70 at 60 min for 10(6) cells/ml. Uptake of higher doses of microcystin (100 nM and more) stopped when the cells blebbed: a toxic response of hepatocytes to microcystin. Uptake of microcystin by hepatocytes was inhibited 70-80% by the addition of 10 microM sodium deoxycholate or bromsulphthlein, compounds that protect hepatocytes from the toxic effects of microcystin. PMID- 1903003 TI - [Preoperative and postoperative magnetoencephalography in a patient with partial epilepsy]. AB - Magnetoencephalography (MEG) is a non-invasive method with a potential of clinical diagnostic use to localize epileptogenic foci in the brain. The aim of this study was to investigate whether the pathological focus localized by MEG was concurrent with the conventional preoperative examinations in a patient with medically intractable epilepsy who underwent surgery (left side uncohippocampectomy). A conventional preoperative test battery had already documented a left-hemisphere fronto-temporal epileptogenic focus. Postoperatively the patient was seizure free. MEG was performed three months before and ten months after the operation. The analysis of the MEG data indicated a left hemisphere fronto-temporal focus in agreement with results obtained by means of the conventional methods used for locating epileptic foci. Postoperatively the focus had disappeared. PMID- 1903004 TI - [Influence of basic health service on mortality in the first 5 years of living in northeast Nigeria]. AB - In the area of the Gongola State, North-East Nigeria, where the Danish Sudan Mission has offered health service since 1913, survival until the 5th birthday has been actuarially calculated based on interviews with pregnant mothers in four areas with different health service intensities: 1. health clinic with medical doctor plus referral hospital, 2. nurse- and midwife health clinic, 3. "medical aide" clinic, and 4. no organized health service. Survivals to 1st birthday were 96, 97, 95, and 87 percent, respectively and to 5th birthday 90, 86, 89, and 68 percent. Differences between the first three groups are small and insignificant, whereas the difference between the area without organized health service and the other areas is highly significant. It is concluded that cost/effectiveness of even the most scanty health service is very favourable, whereas the effect of further health service development is less easily demonstrated. Reservations must be taken because of the limited size of the material and the need for data concerning basic morbidity and mortality in the different areas. PMID- 1903002 TI - Testosterone processing by pituitary cells in culture: an examination of the role of 5 alpha-reduction in androgen action on the gonadotroph. AB - Dispersed rat pituitary cells were exposed to [1,2,6,7-3H]testosterone ([3H]T, 10(-8) M) to assess the role of 5 alpha-reduction in T regulation of gonadotroph secretion. After 4 to 48 hours of exposure, [3H]T metabolites isolated by thin layer chromatography were characterized in medium and cell homogenates as well as bound to androgen receptors salt-extracted from purified nuclear pellets. Receptor-bound 5 alpha-[3H]dihydrotestosterone ([3H]DHT)/total [3H]androgens rose progressively from 16% at 4 hours to more than 50% at 48 hours. Coincubation with 4-MA (10- to 1,000-fold molar excess) or testosterone-17 beta-carboxylic acid (TCA; 1,000-fold excess) reduced receptor-bound [3H]DHT/[3H]androgen to less than 10% and 20%, respectively, but elevated [3H]T-receptor levels. Despite inhibiting 5 alpha-reductase activity, TCA and 4-MA had no effect on T suppression of gonadotropin-releasing hormone-stimulated luteinizing hormone secretion or T enhancement of total (cell + secreted) follicle-stimulating hormone levels. The results suggest that 5 alpha-reduction to DHT is not essential for the expression of the direct influences of T on gonadotropin synthesis and secretion in rat gonadotrophs. PMID- 1903005 TI - Efficiency of bleeding of broilers after gaseous or electrical stunning. AB - The efficiency of bleeding of broilers (g blood/kg liveweight) was measured after stunning them with either 45 per cent carbon dioxide in air for two minutes or with 2 per cent oxygen (achieved by displacing air with argon) for two minutes or with an electric current (77 or 104 mA at 50 Hz for four seconds). The results indicated that the initial rate of bleeding was higher in the electrically stunned broilers with non-fibrillated hearts than in the gas stunned broilers and electrically stunned broilers with fibrillated hearts. This difference was significant up to 60 seconds after neck cutting (P less than 0.05) but after 140 seconds all the broilers had bled out to a similar extent (30 to 33 g/kg liveweight). It is concluded that after gas stunning the time interval between neck cutting and scalding should be 60 to 140 seconds. PMID- 1903008 TI - Economic analyses in hypertension: applications for healthcare providers. AB - Hypertension affects millions of Americans. With healthcare dollars becoming more closely scrutinized, economic studies are playing an important role in helping decision makers choose who should receive treatment and which treatments and methods of administration are most cost-effective. This article provides an overview of the different methods used in economic evaluation and demonstrates the utility of each method using studies from the hypertension literature. PMID- 1903007 TI - Overview of biochemical markers used for nutrition support. AB - Altered metabolism has been shown to exist in the settings of surgical stress, cancer, cirrhosis, sepsis, and trauma. Each condition is characterized by varying degrees of alteration in metabolic processes, and within a given patient, these metabolic alterations will change as the patient's status changes. Nutrition support is an integral part of the metabolic management of critically ill patients. Metabolic changes impact nutritional substrate requirements and utilization. As the patient's clinical condition deteriorates, clinical signs and symptoms become less reliable in predicting or assessing the existing physiologic state. Objective measurements are needed to define the metabolic status during these physiologic changes. The purpose of this article is to review selected indices that have been used to identify abnormalities in nutritional substrate metabolism. Although some of these tests are readily available and inexpensive, many have not been used outside of the research setting and, therefore, their clinical utility has yet to be determined. However, their use as research tools for defining metabolism warrants their inclusion in order to assist the clinician in interpreting research studies. The biochemical markers discussed include glucose, lactate, pyruvate, triglycerides, beta-hydroxybutyrate, acetoacetate, urinary nitrogen, acute phase proteins, visceral proteins, 3-methylhistidine, plasma amino acids, oxygen consumption, and resting energy expenditure. Each marker is defined in terms of its biochemical significance, and the literature describing changes that occur in various stress states is cited. PMID- 1903006 TI - Bovine haptoglobin response in clinically defined field conditions. AB - In order to assess the usefulness of haptoglobin as a measure of the acute phase response in cattle, the concentration of serum haptoglobin was estimated in the non-infectious conditions of milk fever and ketosis, and in the infectious conditions of severe mastitis, acute severe metritis, retained placenta and chronic endometritis. Mean haptoglobin concentrations were normal in cattle with non-infectious conditions and chronic endometritis but significantly increased in cattle with infectious conditions. PMID- 1903009 TI - [Carbon dioxide insufflation in headache and migraine]. PMID- 1903010 TI - Circadian, ultradian, and episodic gonadotropin and prolactin secretion in human pseudocyesis. AB - Six women with pseudocyesis were studied by 15-min blood sampling for 12 to 24 h to determine their gonadotropin and PRL secretory profiles aiming to clarify the endocrine alterations in this form of hypothalamic amenorrhea. Clinical and biochemical evidence of hyperandrogenism was found in 4 patients. Persistent hyperprolactinemia was present only in one patient. Significant circadian and ultradian periodicities were identified by time series analysis in the 12-24 h profiles of FSH, LH and PRL secretion. Pulse analysis by the Van Cauter (UL TRA.JN) method revealed a 24-h mean LH interpulse interval of 91 +/- 21 min with a mean LH amplitude of 5.4 +/- 0.8 IU/l. There was a significantly lower pulse frequency at night than during the daytime. The mean 24-h PRL interpulse interval and pulse amplitude were 134 +/- 22 min and 9.2 +/- 1.8 IU/l, respectively. Both FSH and LH mean levels were higher during the daytime than at night, while the reverse was true for PRL values. Decreased LH pulse frequency and amplitude emerged as the most distinctive findings. Antecedent hypothalamic-pituitary aberrations due to other endocrinopathies and the timing of the hormonal assessment (e.g. recovery phase) may explain, at least in part, the reported heterogeneity of neuroendocrinologic findings in pseudocyesis. PMID- 1903011 TI - Mitotane increases the blood levels of hormone-binding proteins. AB - In 3 patients with adrenocortical carcinoma the effects of long-term mitotane therapy on the serum levels of three hormone-binding globulins and vitamin D binding protein were studied. Within the first month of treatment cortisol binding globulin increased two to three times, in close correlation with sex hormone-binding globulin. The rises in thyroxine-binding globulin and vitamin D binding protein were considerably less. Elevated cortisol-binding protein appeared to be associated with increased binding of cortisol, whereas the binding of thyroxine and vitamin D remained below normal. Binding proteins returned to normal in 2 patients within a year after mitotane discontinuation. This phenomenon of hormone-binding protein enhancement invalidates the use of total serum hormone levels to monitor the effects of mitotane on endocrine function and could provide an explanation for the increased cortisol substitution requirement during mitotane therapy. PMID- 1903012 TI - Evidence for dopamine-related and TRH-related pituitary TSH and PRL pools in patients with prolactinoma. AB - The sources of TSH, which was excessively released by sulpiride (dopamine D2 receptor antagonist), were studied in 15 female patients with PRL-secreting adenoma (18-43 years). Sequential 3-day administration of sulpiride (100 mg, im) was given to 12 patients with prolactinoma and 6 normal female subjects (19-24 years). Patients with prolactinoma showed much greater TSH responses than normal subjects on the first day. However, TSH responses to sulpiride disappeared on the 2nd and 3rd day in both groups. In contrast, plasma PRL responses to the 1st sulpiride administration were smaller in patients with prolactinoma than in normal subjects, and the response disappeared following the 2nd administration in both groups. When TRH (500 micrograms, iv) was administered 120 min after the 3rd sulpiride injection, TSH and PRL increments were not different from those before the sulpiride injection in both patients with prolactinoma (N = 6) and normal subjects (N = 6). Further, combined administration of sulpiride and TRH in 5 patients with prolactinoma clearly enhanced the TSH and PRL responses compared with the single administration of each agent. These results suggest that there may be two readily releasable pituitary TSH and PRL pools, i.e. one dopamine related and the other TRH-related, in patients with prolactinoma and normal female subjects. PMID- 1903013 TI - Histochemical localization of carbonic anhydrase in the female genitalia of pigs during the oestrous cycle. AB - The ovaries and internal genital tracts of cycling gilts were studied for localization of carbonic anhydrase activity using a post-embedding cobalt precipitation technique. Carbonic anhydrase activity was present in selective capillary endothelia and epithelial cells of the genitalia. The ovarian parenchyma, irrespective of the stage of the oestrous cycle considered, was unstained. The secretory cells of the deep furrows in the uterotubal junction and those in the isthmic region of the oviduct of the oestrous female showed a clear membrane-bound localization. The surface epithelium in the tubal ampulla showed a conspicuous cytoplasmic carbonic anhydrase activity during oestrus and the early luteal phase. Neither the intensity nor the localization of the histo-enzymatic reaction in the females varied with their hormonal status (i.e. stage of the oestrous cycle). The localization of the enzyme in particular regions of the female pig genitalia that normally act as sperm reservoirs (uterotubal junction- tubal isthmus) or where fertilization--early embryo development occur (i.e. ampulla) might be related to the control of the acid-base status of luminal fluid. PMID- 1903015 TI - Permanent results of pleoptic treatment. AB - The value of pleoptic treatment was assessed by a long-term follow-up of patients treated 15-22 years ago, employing a questionnaire sent to 232 patients and a clinical examination of a sample of 44 of these. Answers were received from 157 persons with different occupations and educational levels who were fairly representative of the population of Northern Finland as a whole. The treatment was considered beneficial by 62% of these. The primary improvement in the mean visual acuity (VA) from 0.33 to 0.86 among the 44 persons examined proved to be partly transitory, the final mean value being 0.61. The poorest results were found in the combined strabismic and anisometropic amblyopia group. The final VA correlated positively with the initial VA and negatively with age at the time of treatment. Binocular single vision improved the prognosis. Altogether 1/4 of the patients achieved a VA of 1.0 or better, about one half experienced no permanent increase in VA and the remainder were distributed evenly between these two extremes. PMID- 1903014 TI - Immunoelectron microscopic study of synaptic pathology in Alzheimer's disease. AB - Alzheimer's disease (AD) is characterized by an extensive loss of neurons and synapses in the neocortex which correlates strongly with psychometric tests of dementia. To characterize the ultrastructural changes in presynaptic terminals in AD, we studied biopsy material from the frontal cortex. We also examined, at the ultrastructural level, abnormal neurites scattered in the AD neuropil and in the plaque region using sections from autopsy material immunolabeled with anti synaptophysin. We found that, regardless of amyloid deposits, some presynaptic terminals were distended and contained swollen vesicles and dense bodies. These altered synaptic organelles were similar to those found in dystrophic neurites. The latter structures displayed synaptophysin immunoreactivity, mostly localized to outer membranes of synaptic vesicles and dense bodies. The present study supports the hypothesis of progressive synaptic pathology in AD neocortex and favors the notion that the dystrophic process originates from presynaptic terminals. PMID- 1903016 TI - In vitro and in vivo studies with sodium hyaluronate as a carrier for intraocular gentamicin. AB - We compared the in vitro growth of common intraocular pathogens Staphylococcus aureus, Staphylococcus epidermidis and Pseudomonas aeruginosa in rabbit vitreous and in sodium hyaluronate (SH) with and without gentamicin. The minimal inhibitory concentration for gentamicin/SH was 0.5, 0.062 and 2.0 mcg/ml for these pathogens, respectively. After posterior capsulotomy, P. aeruginosa was inoculated into the anterior vitreous and all 15 untreated eyes developed endophthalmitis. In a similar group, aqueous gentamicin administered in the anterior chamber reduced the incidence of endophthalmitis to 10 of 15 eyes. Under similar circumstances, the SH/gentamicin combination lowered the incidence of endophthalmitis significantly to 4 of 15 eyes. The half-life of aqueous gentamicin was 0.9 h, which was shorter than the 2.2 h for SH/gentamicin combination. These results suggest that SH may be a useful carrier for intraocular drug therapy. PMID- 1903017 TI - The utility of infancy weight curves for the prediction of linear growth retardation in preschool children. AB - Routine weight measurements, recorded on health cards of 95 Congolese infants, were collected during a cross-sectional survey as the children were aged 1 to 5 years. The subjects were divided into two groups according to height-for-age (more or less than -2 SD of NCHS reference) at the time of the survey. Adjustment of a mathematical function to the infancy weight curves allowed comparison of groups using the means of the function's parameters: The stunted children had been significantly lighter than the healthy group during infancy. Predictive values of estimated weights and quarterly weight gains were assessed by discriminant analysis and cut-off points were computed. The weight gain between 3 and 6 months of age predicted stunting just as well as weight at age 1 year did. Sensitivity and specificity were at 77% and 74%, respectively. These results suggest that good prediction of stunting is possible from first-year weight measurements. PMID- 1903018 TI - Acute effects of acetazolamide on cerebral blood flow velocity and pCO2 in the newborn infant. AB - Twelve infants with hydrocephalus were treated with acetazolamide. In those treated intravenously middle cerebral artery blood flow velocity increased by a median of 86% (range 54-150%). Maximum increase was reached within 2-20 min. The effect lasted as long as 3.5 hours. Intracranial pressure rose by a median of 4 mmHg (range 0-10 mmHg). There was no significant alteration in blood pressure or heart rate. Respiratory rate increased by approximately 10 breaths/min and the tcpCO2 rose by a median 0.2 kPa in infants with normal lungs. In infants treated orally, blood velocity rose by 35-40% at 60-80 min with no increase in intracranial pressure. In four infants with lung disease pCO2 rose by a median of 2.0 kPa (range 0.6 to 3.4 kPa). Acetazolamide was well tolerated in infants with normal lungs but should be used with caution in the presence of lung disease. PMID- 1903020 TI - Tamoxifen and partial oestrogen agonism in postmenopausal women. AB - The effect of tamoxifen on the vaginal mucosa and on serum oestrone, oestradiol and gonadotrophin concentrations was investigated in a group of nine postmenopausal women with non-metastatic breast cancer. Compared with fit age matched controls, the vaginal pH in the tamoxifen-treated group was significantly lower and was comparable to levels in fertile women. Two thirds of tamoxifen treated women had well oestrogenized vaginal smears compared with none in the control group. Follicle-stimulating hormone was significantly reduced, whilst oestrone and oestradiol levels remained unchanged. We conclude, therefore, that tamoxifen has oestrogen-agonistic properties particularly evident in postmenopausal women, even though it is primarily an antioestrogenic drug. PMID- 1903019 TI - 5-HT2 receptor antagonism in dysthymic disorder: a double-blind placebo controlled study with ritanserin. AB - Thirty patients suffering from dysthymic disorder participated in a 6-week double blind trial comparing ritanserin 10 mg and placebo. After a single-blind placebo wash-out period of one week, the test medication was administered during 5 weeks on a double-blind basis. Twenty-three patients completed the study. At the end of the trial, ritanserin was significantly superior to placebo in its effect as manifested on the 19-item Hamilton Rating Scale for Depression, the Hamilton Rating Scale for Anxiety and the State Trait Anxiety Inventory X-1 and X-2. At the end of the study, the therapeutic effect was rated marked or moderate in 75% of the ritanserin-treated patients, but only in 18% of the controls. These data are consistent with the hypothesis of serotonin abnormalities in dysthymic disorder and suggest a therapeutic role of 5-HT2 antagonists. Ritanserin treatment was very well tolerated; no serious adverse experiences were reported. PMID- 1903021 TI - Diverticula of the female urethra: diagnosis by endovaginal and transperineal sonography. AB - Diverticula of the female urethra can be difficult to diagnose. Invasive contrast studies (voiding cystourethrography or double-balloon urethrography) or urethroscopy are frequently required for definitive diagnosis. Although transabdominal sonography has been able to visualize large diverticula, this technique has not proved useful in routine screening. In this study, we examined the use of higher frequency (5 MHz) near-focus endovaginal or transperineal sonography for the diagnosis of urethral diverticula. Five patients with radiographically proved (three with double-balloon urethrography and two with voiding cystourethrography) urethral diverticula were examined with endovaginal (two cases) or transperineal (four cases) sonography. In all five cases, sonography showed the diverticula previously demonstrated on the contrast study. The spatial relationship of the diverticula to the urethra, an important consideration at surgery, was shown more clearly by sonography than by contrast radiography. These findings suggest that sonography may be useful as a noninvasive screening technique for urethral diverticula. PMID- 1903022 TI - Chest case of the day. Lateral thoracic meningocele in a patient with neurofibromatosis. PMID- 1903023 TI - Randomized phase III study comparing irradiation and hyperthermia with irradiation alone in superficial measurable tumors. Final report by the Radiation Therapy Oncology Group. AB - A total of 307 patients with superficial measurable tumors were registered on a Radiation Therapy Oncology Group (RTOG) protocol involving fractionated radiation therapy, either alone or followed immediately by hyperthermia (42.5 degrees C, 45 60 min). Overall complete response (CR) was observed in 30% of the lesions treated with radiotherapy (RT) and 32% of those receiving RT and heat. Response was found to be significantly related to both maximum tumor diameter (less than 3 or greater than or equal to 3 cm) and site/histology (breast/adenocarcinoma, head and neck/squamous, or other site/histologies). In tumors less than 3 cm in diameter in the breast, trunk, and extremities, a better CR rate was noted with irradiation and heat (62 and 67%) than with irradiation alone (40 and 0%). However, in the head and neck there was only minimal difference in CR with irradiation alone or combined with hyperthermia (50 vs 38%). In lesions less than 3 cm treated with irradiation and heat, there was improved local control. In lesions greater than 3 cm, there was no difference in local control between the two treatment arms. The higher response rate in patients with smaller lesions (less than 3 cm) may be explained by the fact that these tumors are easier to heat. Problems in correlating tumor response with quality of heating include less than optimal heating in larger lesions and the limited ability of current thermometry to map the temperature distribution in a tumor. Acute and late toxicities in both treatment arms were comparable, except for an overall 30% incidence of thermal blisters in the heated tumors. PMID- 1903024 TI - Controversies, dilemmas, and dialogues. The workup of a patient with a positive fecal occult blood test: one procedure? Two procedures? PMID- 1903025 TI - Chronic calcific pancreatitis in a patient with Waldenstrom's macroglobulinemia. AB - We report on a patient with chronic calcific pancreatitis associated with Waldenstrom's macroglobulinemia, and we have hypothesized a possible relationship between these two entities. The hyperviscosity of serum in Waldenstrom's macroglobulinemia may be associated with a viscous pancreatic juice that leads to stone formation. PMID- 1903026 TI - Hemorrhagic disorder due to an isoniazid-associated acquired factor XIII inhibitor in a patient with Waldenstrom's macroglobulinemia. AB - A case is described of a 75-year-old woman with a history of pulmonary tuberculosis and Waldenstrom's macroglobulinemia who developed an inhibitor of coagulation factor XIII while taking isoniazid. The patient presented with a subcutaneous hematoma of the abdominal wall that extended from the xiphoid process to the symphysis pubis and measured 20 cm in diameter. Results of routine coagulation studies were normal with the exception of an increased solubility of the patient's plasma clot in 5M urea consistent with a deficiency of factor XIII activity. Persistence of the deficiency following a 1:2 dilution of the patient's plasma in normal plasma indicated the presence of an inhibitor. A sample of the patient's plasma was depleted of IgG by streptococcal protein G adsorption. The IgG-depleted plasma did not inhibit factor XIII activity, indicating that the inhibitory activity was not attributable to the underlying IgM paraprotein. The patient's purified IgG, on the other hand, inhibited factor XIII activity and the inhibitory activity could be neutralized by anti-IgG antibody. The patient's IgG also inhibited factor XIII-mediated incorporation of fluorescent monodansylcadaverine into casein. Binding of the patient's IgG to factor XIII concentrate was demonstrated by enzyme-linked immunosorbent assay and the IgG that bound to the factor XIII was demonstrated to be polyclonal. Isoniazid was discontinued after the patient was admitted to the hospital. Cryoprecipitate infusion controlled bleeding and reduced the inhibitor titer by 50%. Treatment with cyclophosphamide and prednisone, followed by extracorporeal immunoadsorption over a staphylococcal protein A column, did not reduce the inhibitor titer further. Plasma exchange therapy reduced the inhibitor titer to undetectable levels but failed to restore factor XIII activity. Infusions of factor XIII concentrate reproducibly restored factor XIII activity and were not associated with an anamnestic rise in the inhibitor titer. This represents the seventh reported case of an acquired inhibitor to factor XIII associated with the ingestion of isoniazid. PMID- 1903027 TI - A xanthogranulomatous histiocytosis in a child presenting with short stature. AB - We evaluated a 7-year-old boy presenting with a neck mass that was diagnosed as juvenile xanthogranuloma on excisional biopsy. Despite this diagnosis, an exhaustive evaluation was undertaken because of marked short stature. Examination revealed growth hormone deficiency and diabetes insipidus, as well as widespread lesions in the head, mediastinum, retroperitoneum, skeleton, and elsewhere. Biopsies of the lesions in the mediastinum and right tibia suggested a diagnosis of xanthoma disseminatum with bony involvement, suggesting the Erdheim-Chester variant of xanthogranulomatous histiocytosis, previously reported only in adults. The diagnosis is contrasted to the more common clinical entities of juvenile xanthogranuloma and the Langerhans' cell histiocytoses. This case illustrates the gravity with which otherwise unexplained short stature should be considered. PMID- 1903028 TI - Neuroblastoma screening: arguments from retrospective analysis of three German neuroblastoma trials. AB - The justification for a neuroblastoma screening program has been discussed controversially. The analysis of 701 patients of the German neuroblastoma trials NB 79, 82, and 85 provides additional information on this subject. The basis of our investigation was the good prognosis of stage I and II patients (92% survival 5-10 years after diagnosis) compared with 66% in stage III and 11% in metastatic disease. The correlation of age and stage (p less than 0.0001), a median progression time of 14.6 months (range 3.4-33.5 mo) from localized to metastatic disease as observed in 18 patients, the high incidence of asymptomatic diseases in stages I (49%) and II (30%) patients and the cost-benefit estimation arguments in favor of a screening program. The key problem for the lab part is the lower incidence of abnormal catecholamine metabolite excretion in stage I and II patients. The origin of 89% of metastatic disease from intraabdominal sites suggests that ultrasonography may be of additional value. PMID- 1903029 TI - [A pilot study of the combination of 5-FU and epirubicin for gastric cancer as an adjuvant chemotherapy]. PMID- 1903031 TI - Pure red cell aplasia caused by D-penicillamine treatment of rheumatoid arthritis. AB - A 40 year old woman with rheumatoid arthritis developed pure red cell aplasia after treatment with D-penicillamine 500 mg/day. D-Penicillamine was stopped and short term treatment with steroids resulted in complete recovery of bone marrow. PMID- 1903030 TI - Prophylaxis against non-steroidal induced upper gastrointestinal side effects. PMID- 1903032 TI - Scleroderma 'en coup de sabre'. AB - A case of scleroderma 'en coup de sabre' presenting with uveitis, predominantly posterior, and intractable grand mal seizures is described. The histopathology specimens and neuroradiology investigations reaffirm the clinical impression that inflammation is not solely confined to the skin in this form of linear scleroderma. PMID- 1903033 TI - Influence of bacteria on Clostridium perfringens infections in young chickens. AB - When monoflora chickens with Lactobacillus acidophilus or Streptococcus faecalis were inoculated with Clostridium perfringens either in broth culture or resuspended in Gifu anaerobic medium broth or supernatant fluid, few or no chickens died. Approximately 50% of germ-free chickens died after inoculation of C. perfringens culture, whereas no conventional birds died after inoculation of broth culture. C. perfringens in the contents of duodenum from germ-free chickens numbered about 10(4) colony-forming units (CFU)/g after inoculation 10(8) CFU broth culture per bird, but in gnotobiotic and conventional chickens this organism decreased or was not detected. When C. perfringens was cultured in intestinal contents collected from germ-free chickens, C. perfringens proliferated but alpha toxin was not detected. These findings indicate that the pathogenicity of C. perfringens was suppressed by L. acidophilus or S. faecalis administered previously or inhibited by normal intestinal flora. PMID- 1903034 TI - Cord blood gases and abnormal fetal biophysical assessment in preterm premature rupture of the membranes. AB - The relationship between cord blood gases and infection outcome was determined in 53 consecutive patients with preterm premature rupture of the membranes who were delivered because of abnormal fetal biophysical assessment. Measures of infection outcome included the presence of clinical amnionitis, possible neonatal sepsis, and neonatal sepsis. Fetal acidosis at birth, as defined by cord arterial pH less than 7.20, was found in six fetuses; five of these developed neonatal sepsis and the other was born to a mother who had intrapartum clinical amnionitis. The mean cord blood pH (artery and vein) of fetuses with neonatal sepsis was significantly less than in fetuses with possible neonatal sepsis or no sepsis; however, two thirds (10 of 15) of the neonates with sepsis had normal acid-base status at birth. These data suggest that the fetal biophysical assessment becomes abnormal before the development of fetal acidosis. The possible mechanisms by which fetal infection diminishes fetal biophysical activities prior to the development of acidosis are discussed. PMID- 1903035 TI - Intravenous immunoglobulin for Flavobacterium-induced thrombocytopenia in a premature infant. AB - Gram-negative septicemia at times causes morbidity and mortality in newborn nurseries. Prophylactic intravenous immunoglobulin results in a significant decrease in incidence and severity of septicemia resulting from infection in infants. The present case report describes the successful use of high-dose intravenous immunoglobulin in a Flavobacterium-induced thrombocytopenia in a premature infant. PMID- 1903036 TI - 123I-iodoamphetamine SPECT brain imaging in alternating hemiplegia. AB - Alternating hemiplegia of childhood is an unusual disorder characterized by early onset (occurring before 18 months of age); repeated attacks of hemiplegia involving both sides of the body; other paroxysmal phenomena, such as tonic stiffening, dystonic posturing, choreoathetoid movements, ocular motor abnormalities, and autonomic disturbances, in association with bouts of hemiplegia or occurring independently; and evidence of mental or neurologic deficits. A girl was examined because of left hemiplegia at the age of 16 months. The patient had begun exhibiting episodes of alternating hemiplegia at approximately 4 months of age. They consisted of tonic stiffening and dystonia of the right or left extremities, lasting from 30 min to several hours and followed by residual hemiparesis. They were invariably accompanied by ocular motor abnormalities. Magnetic resonance imaging, computed tomography, and angiography all were normal. Single proton emission computed tomography brain images during an acute episode of right hemiplegia demonstrated hypoperfusion of the left cerebral hemisphere. Following improvement of the hemiplegia, the patient was re evaluated. The uptake of the radiotracer in the left hemisphere was increased. The scan did not demonstrate significant asymmetry in cerebral perfusion. PMID- 1903037 TI - The SOS-Chromo-spottest: evaluation of a short-term test for the determination of genotoxic compounds in contaminated environmental samples. AB - To evaluate the sensitivity of the SOS-Chromo-spottest towards genotoxic compounds 5 reference chemicals (4-nitroquinoline-1-oxide (4-NQO), methylmethansulfonate (MMS), 2,4,7-trinitro-9-fluorenone (TNF), sodium azide (SA) and daunomycin (DM) were tested by 3 different agar plate media (STA-plates: synthetic media containing Xgal, B-plates: synthetic media containing 1% lactose and bromocresolpurple, C-plates: 1% lactose bromocresolpurple media containing complex nutrients). Even 1 ng of 4-NQO showed genotoxic effects by using STA plates. The threshold value for MMS was 80 nl, for TNF 160 ng and for DM 80 ng. Similarly the spottest with B-plates are positive results, but the sensitivity of this test procedure was 80 to 250 times lower than the STA-plate test. The C plate test only reacted with high amounts of 4-NQO (1000 ng). Therefore, the SOS chromo-spottest with STA-media described by Quillardet and Hofnung seems to be a sufficient procedure to detect genotoxic compounds in contaminated environmental samples directly without previous extraction procedures. The simpler B-plates can be used to examine the genotoxicity of certain compounds like industrial or household chemicals where the genotoxicants can be expected to be present in high doses. PMID- 1903038 TI - [Comparative studies of the filtration behavior of bacteria and organic particles in porous groundwater conductors. Fundamentals and methods]. AB - In subsurface aquatic environments two groups of micro-organisms are observed: allochthonous bacteria and viruses, which as contaminants are eliminated from water after some time, and autochthonous groundwater micro-organisms, which belong to the natural subsurface environment and may reach very high abundances under favourable conditions--especially in the presence of a high nutrient supply. The migration of micro-organisms is controlled by flow length dependent transport processes (advection--dispersion, adsorption--desorption), and predominantly by filtration. This can be described on the basis of an expanded advection--dispersion concept. The filter effects in a certain porous aquifer can be quantified by the filter efficiency (filter factor) as a measure of the specific decrease of an initial concentration on a certain flow length. Recent laboratory experiments show that for sand the filter factor depends on the respective microbial species and is highly correlated to the effective grain diameter of the porous material, which is routinely determined in hydrogeology. Experiments with columns filled with quartz sand using the bacteria species Escherichia coli ATCC 11229, Pseudomonas cepacia DSM 50181, Streptococcus faecalis ATCC 6569, and polystyrene beads with similar density and diameters show that the filter factor is controlled by the grain size of filter material, the flow velocity, the diameter of the particle and the ionic strength of the water: The filter factor is specific for each microbial species for the same conditions of the aquatic environment. The filter factor decreases one order of magnitude if the flow velocity increases in the same order. A major control of the filter factor is the grain size. Conventionally the grain size is used as characteristic length instead of the pore size which, although it should be the real reference date, is relatively difficult to measure. For the assessment of the filter factor, the grain size d10, taken from the grain size distribution curve, can be used. The influence of the particle diameter on the filter factor, which was predicted by the filtration theory, was confirmed. The minimum values of the filter factor were encountered at particle diameters of about 1 micron, which is about the size of bacteria. The filter factor is influenced strongly by the ionic strength in water with low ionic strength, whereas in water of higher ionic strength its influence can be neglected. These relationships can be formulated into empirical equations, which allow prediction of the filter factor for given hydraulic conditions. PMID- 1903040 TI - PIS and DRGs: coding inaccuracies and their consequences for resource management. AB - Accurate information is important for the successful implementation of the Resource Management Initiative and the NHS White Paper. A review of 153 joint replacements performed in a three-month period in Leicester showed that 24 per cent of 139 procedures for which medical notes were available had been given incorrect Diagnosis-Related Groupings (DRGs). Of these, 64 per cent could be ascribed to errors in allocating OPCS-3 codes and 36 per cent to errors in converting OPCS-3 codes to DRGs by computer. It is of concern that inaccurate information may in future be used to allocate resources. The resource implications of assiduous quality control of recording, coding and computing is pointed out, and it is suggested that improved classification systems should be assessed for use in the NHS. PMID- 1903041 TI - Communicable disease report. July to September 1990. From the PHLS Communicable Disease Surveillance Centre. PMID- 1903039 TI - The potential of biotechnology to improve the quality of life of patients with renal failure. PMID- 1903042 TI - Coronary thrombolysis: round two and beyond. PMID- 1903043 TI - Life at a price: the implantable defibrillator. PMID- 1903044 TI - 31P and 3-fluoro-3-deoxy-D-glucose 19F in vivo NMR spectroscopy of aged rat brain. AB - 31P and 3-fluoro-3-deoxy-D-glucose (3-FDG) 19F nuclear magnetic resonance (NMR) spectroscopic investigations were performed on aged rat brain in vivo. Phosphodiester (PDE) was found to be significantly higher (p less than 0.05) in aged brain (18 months, n = 10) than adult controls (6 months, n = 10) suggesting accelerated phospholipid catabolism in aged brain. Inorganic phosphate (Pi) levels were significantly lower (p less than 0.05) in aged brain (n = 5) than in normal adult controls (n = 5). The sorbitol index, a measure of aldose reductase activities in vivo, determined by the 3-FDG 19F NMR method, revealed that aldose reductase activities were significantly higher (p less than 0.05) in aged brain. PMID- 1903046 TI - A healthier future. PMID- 1903045 TI - Low levels of serum transport proteins indicate catabolic protein status during induction therapy for acute lymphoblastic leukemia. AB - Twelve children with newly diagnosed acute lymphoblastic leukemia (ALL) were followed during the first 24 weeks of induction and consolidation therapy. Twelve additional patients with other types of cancer, receiving no prednisone medication, served as a reference group. The serum total protein, albumin, transferrin, and prealbumin concentrations were measured at 0, 2, 4, 6-10, 16, and 24 weeks and used as biochemical indices of protein nutritional status. In all patients studied, serum albumin and prealbumin concentrations were low at diagnosis. Decreasing serum total protein and transferrin concentrations, stable low serum albumin, and increasing prealbumin levels were observed during the ALL induction therapy. In contrast, these protein levels remained stable in the children with other malignancies. By week 8 the patients with ALL had lower serum total protein, albumin, and transferrin than the children with other types of cancer. We conclude that the low levels of the serum transport proteins indicate catabolic protein status in children with ALL during early weeks of therapy. PMID- 1903047 TI - A pill for every ill? PMID- 1903048 TI - Leprosy in Brazil. Working at the end of the world. Interview by Michael Gillard. PMID- 1903049 TI - The Clay column. PMID- 1903050 TI - Computers in nursing research. AB - Nicola Eaton launches a four-part, monthly series by considering the range of uses of computer hardware and software for nurse researchers. The other articles in the series will look at expert systems in nursing, computers in nurse education and interactive video as a teaching medium. PMID- 1903051 TI - Attitudes to people with mental handicap. AB - Nurses working with mentally handicapped people may have much to learn from the work and theories of social psychologists. Ron Elvins' wide-ranging article explores some of these theories and looks at how prejudices arise; examples from socio-psychological research serve as illustrations of the problems which integration of population groups present, and perhaps offer models of how integration can be successfully facilitated. PMID- 1903052 TI - Deals and divisions. PMID- 1903054 TI - Excellence in nursing practice. AB - One of the most influential pieces of nursing research in recent years has been the work of Benner (1). She uses a variety of techniques to illuminate and illustrate nursing's complexity. In so doing, she has contributed to that growing body of evidence which helps to show why and how nursing is valuable. Benner often cites vignettes of nursing actions to demonstrate particular nursing interventions, and to analyse skills and knowledge the nurse is using. Vignettes are not designed to be comprehensive case studies or to be well-referenced research projects. Nursing Standard is looking to publish a series of these as part of our contribution to help nurses and others consider the value of nursing; the first, which deals with an example from Steve Wright's experience, follows his introduction to the series, which sets out his view of why nursing matters. PMID- 1903053 TI - Giving information to radiotherapy patients. AB - Patients undergoing radiotherapy treatment have complex fears and anxieties about the therapy and the diseases which have made it necessary. The health care professions have been slow to identify these worries, and have subsequently made few attempts to address them. Beverley Frith's review of the literature demonstrates the different perceptions which have been expressed in relation to this subject and leads her into the identification of the main areas where patients require information. PMID- 1903055 TI - A problem-solving approach to care. PMID- 1903057 TI - Define intervention. PMID- 1903056 TI - Progress of a peacemaker. PMID- 1903058 TI - Empowering women. PMID- 1903059 TI - [Tube feeding]. PMID- 1903060 TI - Use of serum lipid and apolipoprotein concentrations to predict extent of diet induced atherosclerotic lesions in aortas and coronary arteries and to demonstrate regression of lesions in individual rhesus monkeys. AB - In most studies, the assessment of lesion "regression" is based on comparisons of group means between the "progression" and regression groups. This comparison depends on the assumption that the extent and distribution of lesions produced by the end of the lesion-induction period in the regression animals are equal to those observed in the progression group. To determine whether significant regression of lesions occurs in an individual regression animal, it is necessary to obtain a measure of the lesions produced in these animals at the end of the lesion-induction period. We achieved this goal by developing models using multiple stepwise regression analysis that related steady-state serum cholesterol and apolipoprotein B and A-I concentrations measured during a lesion-induction period in 27 rhesus monkeys fed an atherogenic high-saturated-fat/high cholesterol diet for 2 years. The models were developed to estimate the percent of intimal surface with lesions, the esterified cholesterol content (micrograms/cm2) for the artery segments, and three histomorphometric measures (mean intimal thickness, mean maximal intimal thickness, and mean percent stenosis) for the coronary arteries. In these models, multiple R2 ranged from 0.42 to 0.74 for the aortas and peripheral arteries, indicating that approximately one half to three fourths of the variance in lesions was accounted for. For the three histomorphometric measures in coronary arteries, however, the multiple R2 was 0.27 or 0.28, indicating that only approximately one fourth of the variance in lesions was accounted for.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1903061 TI - Increase in plasma cholesteryl ester transfer protein during probucol treatment. Relation to changes in high density lipoprotein composition. AB - Probucol is a hypolipidemic agent that causes a marked decrease in high density lipoprotein (HDL) cholesterol. To investigate the mechanism of this effect, two studies were performed in hypercholesterolemic patients who had been stabilized previously on diet and were not receiving other lipid-lowering medication. Plasma cholesteryl ester transfer protein (CETP) concentrations were measured in fasting plasma samples before and after 10 weeks of probucol therapy using a sensitive and specific radioimmunoassay. Plasma total and low density lipoprotein cholesterol concentrations decreased, whereas apolipoprotein (apo) B was unchanged. Plasma apo E concentrations increased markedly. HDL cholesterol and apo A-I decreased in all subjects. These effects of probucol were accompanied by even more striking changes in plasma CETP concentrations, which increased by a mean of 64%. In a second study of six hypercholesterolemic subjects, the time course effects of probucol on CETP and HDL subspecies were studied. Significant increases in plasma apo E and in CETP occurred after 4 weeks, and CETP, but not apo E, increased further after 16 weeks of treatment. Concomitant and opposite changes occurred in HDL composition, with decreases in HDL cholesterol and lipoprotein containing apo A-I. The increase in plasma CETP concentrations, the decrease in HDL cholesterol, and the increase in plasma apo E concentrations observed during probucol treatment are changes consistent with a postulated increase in reverse cholesterol transport via the remnant pathway. PMID- 1903062 TI - Synthesis of prostaglandins and thromboxane B2 by cholesterol-fed rabbits. AB - Alterations in the synthesis of thromboxane A2 (TxA2) and prostacyclin have been implicated in the development of atherosclerosis. We measured the amounts of the degradation products of these substances, TxB2 and 6-oxo-prostaglandin F1 alpha (6-oxo-PGF1 alpha), respectively, as well as PGE2, that were synthesized by slices and the luminal surfaces of aortas from rabbits fed either a control diet or a diet supplemented with cholesterol and peanut oil. For these studies, we developed conditions that were designed to minimize the autoinactivation of cyclooxygenase during removal and preparation of the tissue. Pretreatment of aortas with a medium containing ibuprofen and EDTA resulted in an approximately twofold increase in 6-oxo-PGF1 alpha production upon subsequent incubation. Despite the increased lipid peroxidation associated with atherosclerotic lesions, we observed no changes in either aortic 6-oxo-PGF1 alpha production or in the levels of its major urinary metabolite, 2,3-dinor-6-oxo-PGF1 alpha, after as long as 15 weeks of dietary supplementation with cholesterol and peanut oil. Similarly, synthesis of PGE2 by aortic slices and the aortic lumen was the same in cholesterol-fed and control rabbits. In contrast to aortic 6-oxo-PGF1 alpha and PGE2 synthesis, there was a dramatic 10-fold increase in TxB2 released from slices of thoracic aorta after 15 weeks on the atherogenic diet. This was much greater than the approximately twofold increase in the synthesis of TxB2 by the luminal surface of the thoracic aorta, suggesting that the primary site of TxB2 synthesis in the aorta is in the inner part of the blood vessel.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1903063 TI - Age and dietary polyunsaturated fat alter high density lipoprotein subfraction cholesterol concentrations in a pediatric population of African green monkeys. AB - African green monkeys were raised from birth to 60 months of age on diets containing cholesterol (0.8 mg/kcal) and enriched in polyunsaturated (polyunsaturated to saturated fat ratio [P:S] = 2.5) or saturated (P:S = 0.3) fat. Lipoproteins were isolated from plasma of a group of animals (N = 123) and were separated by gel filtration chromatography at 9, 14, 26, 38, and 50 months of age, which covered a period through adolescence into young adulthood. Total plasma cholesterol (TPC) concentrations were 16% lower (p = 0.01) in the polyunsaturated fat-fed group, and high density lipoprotein (HDL) cholesterol concentrations averaged 20% lower (p = 0.008) in this group between 14 and 50 months of age, while plasma apolipoprotein A-I (apo A-I) averaged 7% lower (p = 0.06) over this age interval in the animals. The HDL cholesterol to apo A-I ratio was found to be significantly lower (p = 0.006) in the animals fed the polyunsaturated fat diet. This suggested that the HDL subfraction distribution might differ between groups. In a subset of animals (n = 105, 64 male and 41 female), HDL was subfractionated by density gradient ultracentrifugation into six subfractions, HDL-I to HDL-VI, from lowest to highest density. The saturated fat fed animals had significantly higher cholesterol concentrations in HDL-I and significantly lower cholesterol concentrations in HDL-III, HDL-IV, and HDL-V. These effects held across all ages studied; therefore, these diet effects were not age dependent. In both diet groups, the HDL subfraction pattern changed with age such that the HDL-I and HDL-II cholesterol concentrations decreased, and those of HDL-IV, HDL-V, and HDL-VI increased as the animals matured. The decrease in HDL-I with age appeared to result primarily from a decrease in HDL-I in males, while the HDL-I cholesterol concentration in females did not change with age. We conclude that diet, age, and gender all affect HDL subfraction distribution and therefore can potentially modify the relative atherogenicity of the plasma HDL populations. It remains for future studies to demonstrate the effectiveness of each subfraction in promoting or preventing the cholesterol deposition of atherosclerosis. PMID- 1903064 TI - Characterization of a human high density lipoprotein-associated protein, NA1/NA2. Identity with SP-40,40, an inhibitor of complement-mediated cytolysis. AB - Two peptides, NA1 and NA2, which we previously suggested to be associated with high density lipoproteins (HDLs), have been purified. Polyclonal antibodies against each peptide and a monoclonal antibody against NA2 have been used to further characterize them and their association with HDL. Immunoblotting studies revealed that the peptides form a complex of molecular mass of approximately 80 kd. Agarose gel filtration showed coelution of NA1/NA2 and apolipoprotein (apo) A I, the structural protein of HDL. This was confirmed by fast protein liquid chromatography, which further indicated that up to 60% of NA1/NA2 was located within the lower density range of the HDL spectrum. Complementary studies with anti-apo A-I immunoaffinity columns provided evidence that at least 40% of NA1/NA2 was associated with HDL, an association easily disrupted by ultracentrifugal manipulation. Finally, partial amino acid sequences showed virtually complete homology with a recently identified protein, SP-40,40, or cytolysis inhibitor. The protein is suggested to have a powerful inhibitory effect on complement-mediated cell lysis. Our results could thus furnish an explanation for the previously observed modulating influence of HDL on complement activity. PMID- 1903066 TI - Hemolytic and antimicrobial activities of the twenty-four individual omission analogues of melittin. AB - Although melittin's hemolytic activity has been extensively studied, the orientation of membrane-bound melittin remains uncertain. We have investigated the effect of individually omitted amino acid residues on melittin's activity and related these results to the existing models of melittin-membrane interaction. The extent of hemolysis of the omission analogues closely followed the four known conformational regions of melittin: omission of any of the residues making up the two alpha-helical regions decreased the hemolytic activity relative to melittin, while omission of any of the residues making up the "hinge" or the C-terminal regions had little or no effect. Our results correlate best with a proposed model in which melittin initially forms "holes" in the membrane, resulting in an initial rapid loss of hemoglobin; the membrane-bound melittin is then internalized into the membrane, resulting in a later slow phase of hemoglobin loss. It was also found that induced structural effects caused by peptide-lipid interactions could be studied by using RP-HPLC, with an excellent correlation found between the retention times of the individual omission analogues and their hemolytic activities. PMID- 1903065 TI - Variable effects of different corticosteroids on plasma lipids, apolipoproteins, and hepatic apolipoprotein mRNA levels in rats. AB - Treatment of male rats with hydrocortisone provoked a dose- and time-dependent decrease in plasma cholesterol concentration without a change in plasma triglyceride levels. In contrast, administration of triamcinolone and dexamethasone at equipotent glucocorticoid doses increased plasma cholesterol and triglyceride levels, respectively. Small effects on apolipoprotein E (apo E) and apo B mRNA levels were observed, but all corticosteroids increased apo A-I and apo A-IV mRNA and decreased apo A-II mRNA levels in the liver. Triamcinolone and dexamethasone, however, were three times more potent in stimulating hepatic apo A IV gene expression than was hydrocortisone, whereas liver apo A-I and apo A-II mRNA levels were altered to a similar extent by all corticosteroids. Plasma apo A I and apo B concentrations always varied in a similar fashion with their respective liver mRNA levels after administration of the distinct corticoids. For apo A-IV and apo E, discrepancies between plasma and liver mRNA levels after administration of the different steroids, however, point to additional regulatory effects on plasma apolipoprotein levels. We conclude that 1) in contrast to plasma apo A-I and apo B, alterations in plasma lipid, apo A-IV, and apo E levels depend on the type of corticosteroid used; and 2) glucocorticoids have a differential effect on hepatic mRNA levels of apo A-I and apo A-IV on the one hand and apo A-II on the other hand, an effect that may be of consequence in the process of reverse cholesterol transport. PMID- 1903067 TI - Stimulation of the amidolytic activity of single chain tissue-type plasminogen activator by fibrinogen degradation products: possible fibrin binding sites on single chain tissue-type plasminogen activator molecule. AB - The steady-state kinetics of the amidolytic activity of single chain tissue-type plasminogen activator (tPA) were analyzed in the presence or absence of different molecular forms of fibrinogen degradation products. Single chain tPA showed a Km value of 1.6 mM and kcat value of 4.9/s toward the chromogenic substrate H-D-Ile Pro-Arg-p-nitroanilide (S-2288). In the presence of infinite concentrations of fibrinogen, kinetic constant was calculated as about 8-times higher than that in the absence of fibrinogen, mainly caused by the decrease of Km value. The dissociation constant (Ka) for this stimulation by fibrinogen was 2.9 microM. When the same assay was conducted with fragment X or fragment D of fibrinogen, the kinetic constants increased 3.2 and 2.9-times, respectively, whereas no enhancement was obtained by fragment E. Neither lysine analogues nor monoclonal antibody toward domains of finger and epidermal growth factor of tPA quench the enhancement by fibrinogen. This enhancement was not observed in the case of the two chain form of tPA. These results indicate that fibrinogen enhances the amidolytic activity of single chain tPA by binding to kringle 2 domain or light chain through D domain of fibrinogen. PMID- 1903068 TI - Isolation of three forms of cystatin from submandibular saliva of isoproterenol treated rats, its properties and kinetic data. AB - Three rat salivary cystatins (designated as RSC-1, RSC-2 and RSC-3) induced by chronic isoproterenol (IPR) treatment, but not detected in normal rats, were purified from submandibular saliva of chronically IPR-treated rats by Mono-Q, hydroxyapatite and TSKgel Phenyl-5PW chromatographies. Their molecular weights (Mr) and isoelectric points (pI) differed from each other as follows: RSC-1 (Mr 16,500, pI 4.4), RSC-2 (Mr 15,500, pI 4.4) and RSC-3 (Mr 14,500, pI 4.5). The amino acid compositions of these inhibitors were very similar and the three forms showed complete immunological identity in a double immunodiffusion system. The partial amino acid sequence results showed that these inhibitors belonged to family 2 of the cystatin superfamily. These three forms strongly inhibited the enzyme activities of ficin and papain, but not of cathepsin B and trypsin. The inhibition constants (Ki) of RSC-1, RSC-2 and RSC-3 for ficin were 0.19, 0.50 and 0.012 nM, and for papain were 1.5, 0.93 and 0.03 nM, respectively. RSC-3 inhibited ficin and papain more strongly than did RSC-1 and RSC-2. PMID- 1903069 TI - Hypercholesterolaemia: simvastatin and pravastatin alter cholesterol metabolism by different mechanisms. AB - The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor simvastatin, reduced low-density-lipoprotein (LDL) cholesterol in hypercholesterolaemic patients by 40% (P less than 0.001). The reduction in LDL cholesterol was accompanied by a significant decrease in the esterified/free cholesterol ratio of the patients' LDL from 2.51 +/- 0.13 to 2.06 +/- 0.14 (P less than 0.01). This change led to a significant increase (P less than 0.05) in the capacity of the LDL to suppress [14C]acetate incorporation into cholesterol in mononuclear leucocytes. Furthermore, [14C]acetate incorporation into the patients mononuclear leucocytes was significantly lower (P less than 0.02) following drug treatment (117 +/- 22 vs. 162 +/- 29 nmol/mg cell protein). Comparison of simvastatin with another HMG-CoA reductase inhibitor pravastatin, showed similar reduction in LDL cholesterol. Pravastatin treatment however, did not result in a reduction in the LDL esterified/free cholesterol ratio or in the changes in cellular cholesterol synthesis and its regulation by LDL which accompanied simvastatin treatment. The activity of the enzyme acyl-coenzyme A: cholesterol acyltransferase (ACAT) in patients' mononuclear cells remained unchanged after treatment with either drug. Results of the study show that while the drugs are equally effective in lowering LDL cholesterol, simvastatin has additional compositional effects on LDL which increase its capacity to regulate mononuclear leucocyte cholesterologenesis. PMID- 1903070 TI - Hemin and hemeprotein bleaching during linoleic acid oxidation by lipoxygenases. AB - Hemin and hemoglobin are bleached by lipoxygenases, type 1 (from soybean) or type 2 (from platelets), during linoleic acid oxidation. This process has been found to be related to the inhibition of the lipoxygenase activity, measured as hydroperoxide generation and to produce oxodienes as well. All these parameters have been determined simultaneously from measurements of the absorbance at 234, 285, 375 and 410 nm to detect hydroperoxides, oxodienes, hemin and hemoglobin, respectively, using a diode array spectrophotometer. The inhibition of lipoxygenase activity by these pigments has been found to be competitive with linoleic acid, showing an increase of 4-7-fold of the Km value of linoleic acid in the presence of concentrations of hemin and hemoglobin as low as 0.2 and 0.02 microM, respectively, for the case of platelet lipoxygenase activity. The concentrations of hemin and of hemoglobin producing the inhibition of 50% of lipoxygenase activity are: 0.25 and 0.02 microM for the platelet isoenzyme, and 1.4 and 0.18 microM for the soybean isoenzyme, respectively. From the quenching of the intrinsic fluorescence of soybean lipoxygenase activity by hemin, we have obtained a dissociation constant of hemin-soybean lipoxygenase of 0.5 microM. The results obtained in this paper for the cooxidation process of hemin and hemoglobin by lipoxygenase can be rationalized in terms of hemin binding at or near to the catalytic center, resulting in a lesser binding of linoleic acid and an enhanced release of radicals, and pigment bleaching by radicals and lipid hydroperoxides. PMID- 1903071 TI - [Osteoarticular infections associated with catheterization of the subclavian vein]. AB - Access to a central way through catheterization of the subclavian vein is a widely used technique. Not uncommonly, the procedure is followed by infective complications among which clavicular osteomyelitis and septic sternoclavicular arthritis represent a rare eventuality. We report two cases of staphylococcic bacteremia produced after subclavian vein catheterization. Both patients presented septic sternoclavicular arthritis and osteomyelitis of the sternal manubrium. The isolated microorganisms were Staphylococcus aureus and Staphylococcus epidermidis methicillin-resistant, respectively. The clinical course under antibiotic therapy was satisfactory in both cases. Septic metastases appear to be the most likely pathogenic mechanism for the osteoarticular complications. PMID- 1903072 TI - [Pneumonia caused by Branhamella catarrhalis. A well-documented case]. PMID- 1903073 TI - Synergistic effect of recombinant interferon-gamma and interleukin-3 on the growth of immature human hematopoietic progenitors. AB - Purified peripheral blood hematopoietic progenitors from children in early remission from cancer respond to recombinant human interleukin-3 (IL-3), but not to granulocyte colony-stimulating factor (G-CSF). With these purified cells as a target, we studied the effect of recombinant human interferon-gamma (IFN-gamma) on progenitor growth, using both liquid-suspension limiting dilution assay (LDA) and regular methylcellulose culture of progenitors. We found that in LDA with IL 3, IFN-gamma directly stimulated the growth of blood progenitors in a dose dependent manner with single-hit kinetics, whereas IFN-gamma suppressed the growth of G-CSF-supported progenitors obtained from bone marrow. The stimulatory effect was also observed in methylcellulose culture, but the addition of antibodies for G-CSF, granulocyte-macrophage CSF, IL-1 alpha, IL-1 beta, IL-6, or tumor necrosis factor did not result in a decrease of the colony number, supporting further the possible direct effect of IFN-gamma on progenitor growth. These results suggest that the inhibitory effect of IFN-gamma on hematopoietic progenitors is limited to those in an advanced stage of maturation. IFN-gamma may be one of the essential lymphokines upregulating the growth of human hematopoietic progenitor cells. PMID- 1903074 TI - Effect of interleukin-9 on clonogenic maturation and cell-cycle status of fetal and adult hematopoietic progenitors. AB - We assessed the effect of interleukin-9 (IL-9) on clonogenic maturation and cell cycle status of hematopoietic progenitors of fetal (umbilical cord blood) and adult (bone marrow) origin. As a single agent IL-9 supported, in a concentration dependent fashion, maturation of burst-forming units-erythroid (BFU-E) of adult and fetal origin. However, only 1/3 the number of adult BFU-E colonies developed, as did in response to granulocyte-macrophage colony-stimulating factor (GM-CSF), and only 1/6 the number developed as did in response to IL-3. In contrast, the effect of IL-9 on fetal BFU-E colonies was equal to that of GM-CSF and IL-3. Synergistic effects of IL-9 with low concentrations (0.1 ng/mL) of GM-CSF and IL 3 were seen on adult BFU-E colony formation, but no effect was apparent at higher concentrations (1.0 ng/mL). In contrast, using fetal cells, synergistic effects of IL-9 with low and high concentrations of GM-CSF and IL-3 were apparent. Addition of IL-9 to plates containing fetal cells plus GM-CSF and IL-3 not only resulted in more BFU-E colonies, but also in more multicentered (greater than or equal to 10 individual centers) colonies, and more cells per colony. IL-9 had a wider spectrum of action on progenitors of fetal origin than on progenitors of adult origin, supporting the generation of fetal multipotent colony-forming unit (CFU)-Mix and CFU-GM colonies. Incubation with IL-9 did not accelerate cycling of adult or fetal BFU-E, CFU-Mix, or CFU-GM to the extent observed after incubation with IL-6. Thus, IL-9 primarily supported maturation of erythroid progenitors of adult origin, and its addition to plates containing GM-CSF and IL-3 (1.0 ng/mL) did not result in maturation of additional clones. In contrast, IL-9 had a wider spectrum of action on fetal progenitors and, when combined with IL-3 and GM-CSF, resulted in clonogenic maturation of progenitors that did not undergo maturation after stimulation with IL-3 and GM-CSF. PMID- 1903076 TI - A genetic defect causing Alzheimer's disease. PMID- 1903075 TI - Leukemia inhibitory factor can potentiate murine megakaryocyte production in vitro. AB - Receptors for murine leukemia inhibitory factor (LIF) were demonstrated on immature and mature murine megakaryocytes. LIF alone had no effects in culture on the survival or proliferation of normal murine megakaryocytes or their precursors. However, combination of LIF with multipotential-colony-stimulating factor (Multi-CSF) (interleukin-3) enhanced the megakaryocyte colony formation able to be stimulated by Multi-CSF; the enhancement involved all types of megakaryocyte colony and resulted in the formation of increased numbers of megakaryocytes. These observations provide a possible basis for the observation that, when LIF is injected in vivo, elevations are observed in megakaryocyte numbers and platelet levels. PMID- 1903077 TI - Fluoxetine and fluvoxamine. PMID- 1903078 TI - The immune response. 2. Systemic mediators of inflammation. AB - This article deals with the mechanisms by which local immune stimulation is transmitted to the periphery, leading to systemic inflammation. We concentrate on the role of three signalling molecules: interleukin-1, interleukin-6, and tumour necrosis factor alpha. These cytokines provide a direct link between local and systemic inflammation. PMID- 1903079 TI - Dihydroergocryptine in the treatment of Parkinson's disease: a six months' double blind clinical trial. AB - The short-term efficacy of dihydro-alpha-ergocryptine (DEK), a hydrogenate ergot derivative with dopamine (DA) agonist properties was evaluated in 20 L-dopa (LD) stable responder parkinsonian patients by a 6-month double-blind randomized, placebo-controlled study. A motor improvement was found only in DEK-treated patients at mean daily doses of approximately 40 mg, ranging from 15 to 60 mg. The side effects never required the withdrawal of the drug or changes in its schedule. The authors demonstrate the efficacy and the good tolerability of DEK as a new DA agonist drug that can be added to LD in the treatment of parkinsonian patients. PMID- 1903080 TI - Single bolus administration of recombinant tissue plasminogen activator: effects on infarct related vessel patency, microvascular perfusion, and microvascular reocclusion in a canine model of thrombotic occlusion/reperfusion. AB - STUDY OBJECTIVE: The aim was to evaluate the thrombolytic efficacy of recombinant double chain tissue plasminogen activator (Duteplase, t-PA) given as a single intravenous bolus versus an infusion in a canine model of coronary arterial occlusion/reperfusion. DESIGN: Coronary arterial thrombi were induced by a copper coil (placed under fluoroscopic control) in the left anterior descending coronary artery of anaesthetised dogs. Following 90 min thrombotic occlusion, animals were randomly assigned to one of two treatment groups: group 1 = t-PA infused intravenously at 0.6 x 10(6) IU.kg-1.h-1, or group 2 = t-PA (0.6 x 10(6) IU.kg-1) by intravenous bolus over 6 min. Both groups received concurrent heparin (six 1000 IU boluses, + 100 IU.kg-1.h-1) throughout t-PA administration and the 2 h reperfusion period. SUBJECTS: 16 beagle dogs of either sex were used, weight 9.2 20.3 kg. MEASUREMENTS AND MAIN RESULTS: Radiolabelled microspheres were injected to assess microvascular coronary flow at various time points throughout the experimental period. Infarct related vessel patency (IRVP) was assessed arteriographically every 5 min. Infarct size was assessed histochemically at the end of the reperfusion period. IRVP was achieved within 42.9 (SEM 7.4) min and 43.1(7.0) min for infusion and bolus groups respectively; 60 min patency rates were 88% for both groups. t-PA restored full microvascular flow to ischaemic subendocardial and subepicardial regions in both groups compared to initial preocclusion regional blood flow. Extent of reactive hyperaemia was greater in infusion than bolus treatment animals: infusion group 1.18(0.15) v bolus group 0.72(0.14) ml.min-1.g-1 (subepicardial). Degree of microvascular reocclusion at 120 min reperfusion was similar for both groups despite aggressive anticoagulation throughout: infusion group 0.33(0.08) v bolus group 0.42(0.11) ml.min-1.g-1 (subendocardial). Areas of the myocardium at risk (R), absolute infarct size (I), and infarct risk ratio (I/R) were similar for both groups: R = 33.9(1.5) v 30.9(1.9)%; I = 15.9(3.1) v 13.3(3.1)%; I/R = 46.3(8.4) 42.1(9.2)%. Degree of systemic fibrinogenolysis was similar for both groups: infusion 1.65(0.40) to 0.67(0.07) g.litre-1 v bolus 1.68(0.15) to 0.96(0.12) g.litre-1. CONCLUSIONS: Single bolus administration of t-PA showed equivalent efficacy to infusion dosing in respect of IRVP, microvascular reperfusion, and microvascular reocclusion. As a result the degree of tissue necrosis (I/R ratio) was no different when comparing the two dosing regimens. Similar degrees of systemic fibrinogenolysis were observed for both treatment groups. PMID- 1903081 TI - Frequency dependent effects of tocainide, quinidine, and flecainide on conduction as reflected in the rise time of the monophasic action potential in the isolated guinea pig heart. AB - STUDY OBJECTIVE: The aim was to evaluate a possible correlation between intraventricular conduction and the rise time of the ventricular monophasic action potential upstroke. DESIGN: This evaluation was performed by estimating the onset rate kinetics for changes in the monophasic action potential rise time and cardiac conduction upon abrupt shortening of the interstimulus interval in the in vitro perfused guinea pig heart. EXPERIMENTAL MATERIAL: 21 Duncin Hartley guinea pigs, 520-800 g, were used for the studies. The animals were anaesthetised and the hearts rapidly excised and perfused horizontally in the Langendorff manner. MEASUREMENTS AND MAIN RESULTS: It was shown that the rise time onset rate (expressed as the inverted number of action potentials needed to reach 63% of the new steady state level) was very fast (greater than 0.5) for tocainide, very slow for flecainide [0.09(SEM 0.009]) and intermediate for quinidine [0.29(0.070)]. These values are similar to onset rates previously reported from studies of Vmax in intracellular recordings. Moreover, similar onset rates were obtained for simultaneously measured frequency dependent changes in cardiac conduction. CONCLUSIONS: These findings suggest that, at least for drugs restricting sodium entry into the cell, effects on Vmax could be predicted from monophasic action potential rise time data from the isolated guinea pig heart. The possibility of using the monophasic action potential rise time as a measure of local cardiac conduction provides an opportunity for in vivo studies of the temporal beat by beat relationship between conduction and repolarisation, factors that are important for the initiation and maintenance of many arrhythmias. PMID- 1903082 TI - Antiarrhythmic drugs preferentially produce conduction block at the area of slow conduction in the re-entrant circuit of canine atrial flutter: comparative study of disopyramide, flecainide, and E-4031. AB - STUDY OBJECTIVE: The aim was to test whether antiarrhythmic drugs preferentially suppressed conduction in the area of slow conduction in the re-entrant circuit. DESIGN: Intravenous disopyramide [n = 8, plasma concentrations: 1.4 (SEM 0.2) micrograms.ml-1], flecainide [n = 8, 0.6(0.1) micrograms.ml-1], and E-4031, a new class III antiarrhythmic drug [n = 8, 5.6(1.0) ng.ml-1], were investigated for their effects on atrial flutter due to re-entry in dogs with intercaval crush. In three dogs, detailed atrial activation sequence during atrial flutter was determined with a hand held bipolar electrode and an epicardial isochronal map was drawn. EXPERIMENTAL MATERIAL: 24 anaesthetised adult mongrel dogs were used. MEASUREMENTS AND MAIN RESULTS: There was an area of slow conduction during atrial flutter in the low right atrium. Atrial flutter was terminated in all dogs except for one treated with flecainide. In 92% of the dogs, conduction block occurred in the low right atrium in which the area of slow conduction was located. Increase in local conduction time was greater in the area of slow conduction than other parts of the atria (percent ratio to the increase in cycle length of atrial flutter: 63% with disopyramide, 52% with flecainide, and 99% with E-4031). CONCLUSION: These data suggested antiarrhythmic drugs preferentially suppressed conduction at the area of slow conduction in the re-entrant circuit leading to termination of atrial flutter in this canine model, irrespective of electrophysiological effects of antiarrhythmic drugs. PMID- 1903083 TI - Microbial-host interactions in the airways in chronic respiratory infection. AB - The pathogenic events that take place in chronic respiratory infection highlight the successful microbial strategy of survival by persistence, or colonization. Microorganisms implement their strategy of persistence by two principal tactics: (1) sabotage of the host's bronchial defenses (ie, direct microbe-mediated damage to the host), and (2) subversion of the host's normally protective defenses into damaging host tissue itself (ie, indirect host-mediated damage provoked by the microbe). Among the various ways in which microorganisms directly damage host defenses and facilitate their own persistence in the respiratory tract are inhibition of ciliary function, inhibition of mucociliary transport, alteration of ion transport in respiratory epithelium, stimulation of mucus production, and damage to respiratory epithelium. Patients with chronic respiratory infection suffer a vicious circle of events leading to progressive lung damage and cardio respiratory failure. Treatments to break this circle include antimicrobial therapy to reduce microbial colonization and anti-inflammatory/immunosuppressive therapy to modulate damaging host responses. PMID- 1903084 TI - Electron microscopic changes on the DMBA induced oral precancerous and cancerous lesion in hamster cheek pouch. AB - Experiments were performed to study the early and late ultrastructural changes during hamster cheek pouch carcinogenesis using a regimen of topical application of 9,10 dimethyl-1-1-2 benzanthracene (DMBA) twice a week in liquid paraffin oil. The DMBA was administered for a period of 2 and 4 1/2 months. Hamsters exposed to DMBA for 2 months developed moderate precancerous changes, whereas the hamsters treated with DMBA for 4 1/2 months developed frank and multiple oral tumors with a cauliflower appearance. The ultrastructural pathological changes seen were considerably increased at 4 1/2 months compared with a 2 month period of DMBA treatment. Untreated and solvent control hamsters cheek pouch treated for 2 and 4 1/2 months with liquid paraffin oil alone did not show any premalignant or malignant changes during this period. PMID- 1903085 TI - On the association of DNA polymerase alpha activity with the nuclear matrix in HeLa cells. AB - The association of DNA polymerase alpha activity with the nuclear matrix has been reinvestigated in HeLa cells. Isolated nuclei were extracted with 2M NaCl and then digested with Dnase I and the final structures were recovered by centrifugation through a sucrose cushion. Typically over 98% of the total DNA synthesized in the matrix fraction on either endogenous matrix-associated DNA or activated calf thymus DNA was due to DNA polymerase alpha as defined by inhibition to n-ethylmaleimide or aphidicolin. DNA polymerase beta activity was absent or recovered in only trace amounts. Matrix-bound DNA polymerase alpha activity demonstrated a remarkable degree of stability: DNA synthesis was essentially linear up to 3 hours at 37 degrees C. Overall, these results substantiate previous findings from regenerating rat liver, unlike other data obtained from tissue culture cells. PMID- 1903086 TI - A structural protein that plays an enzymatic role in the eggshell of Drosophila melanogaster. AB - E.S.P. is responsible for the hardening process of the egg-shell at the end of oogenesis (stage 14B) and constitutes a structural component. By immunoblotting, using polyclonal rabbit anti-HRP antibody and anti-rabbit IgG-HRP or Protein A 1251 as second antibody, one major band with MW 38KD on nitrocellulose filter showed positive reaction. We conclude that the E.S.P. is identical to the S38 chorionic protein. Morphological immunogold staining, using pre-embedding procedure, revealed positive reaction in the innermost chorionic layer (ICL) and the endochorion of the eggshell. In addition, electron probe X-ray microanalysis revealed the existence of 37% calcium (explained since the enzyme is Ca2(+) activated) and 5% iron (explained due to the fact that it is a haemoprotein). PMID- 1903087 TI - Changes in glycosaminoglycan expression in the rat developing intestine. AB - Synthesis of glycosaminoglycan (GAG) chains was studied in the developing rat intestine. Intestinal segments, taken at various developmental stages, were exposed to 3H-glucosamine and 35S-sulfate for 6 hours. The amounts of 3H-GAGs (total GAGs) and of 35S-GAGs (sulfated GAGs) showed a clear age-dependence, with a broad maximum in the fetal period when dramatic growth and morphogenesis occur. Characterization of individual GAG species indicated that hyaluronic acid (HA), heparan and chondroitin sulfate (HS and CS) synthesis was modified quantitatively or qualitatively during development: decrease of HA with age; production of undersulfated HS molecules during embryonic life; shift towards a lower hydrodynamic form of HA and HS molecules after birth. We postulate that these alterations are crucial in the elaboration of an age-related specific extracellular microenvironment allowing intestinal growth and differentiation. PMID- 1903088 TI - Cutaneous anthrax--British Columbia. PMID- 1903089 TI - Wide spectrum detection of precarcinogens in short-term bioassays by simultaneous superinduction of multiple forms of cytochrome P450 isoenzymes. AB - The use of Aroclor 1254 to induce S9 liver fractions is a standard method for conducting short-term genotoxicity assays. An alternative induction procedure, using beta-naphthoflavone (beta-NF), as a safe (non-carcinogenic) substitute for polychlorinated biphenyls, combined with sodium phenobarbital (PB), was found to be equally effective. The aim of this work is to realize a novel schedule of induction for the preparation of metabolizing systems containing a wider spectrum of induced cytochrome P450s. Five inducers of different 'classes' such as PB (class IIB P450s), beta-NF (IA), isosafrol (IA2), ethanol (IIE1) and pregnenolone 16 alpha-carbonitrile (IIIA) were injected daily both separately (to achieve maximal monooxygenase induction) in male and female mice. Induction was monitored using specific P450-linked activities. In the optimal schedule for complete induction, the various monooxygenases were greater (2- to 4-fold) than those achieved by the classical schedule. More than a 14-fold increase of total P450 and 3.3-fold increase of NADPH-cytochrome (P450) c-reductase activity, over those uninduced, account for the above increase. For example, there was a marked increase in the deethylation of ethoxyresorufin (37-fold) compared to the uninduced mice that was considerably higher than classical induction (8-fold over uninduced). On the contrary, phase II reactions i.e. epoxide hydrolase, glutathione S-transferase, glutathione S-epoxide transferase and UDP-glucuronosyl transferase, examined to compare the phase I/phase II ratios in the traditional and proposed procedures, were increased to a lesser extent (2-fold over uninduced). No significant sex differences were seen. Five precarcinogens specifically metabolized by each of the induced P450s elicited a higher mutagenicity response in the presence of superinduced fractions with respect to the classical one, when tested on Salmonella typhimurium (cyclophosphamide, benzo[alpha]pyrene, 2-naphthylamine and dimethylnitrosamine) or Saccharomyces cerevisiae D7 strain (diethylstilbestrol). These novel metabolizing biosystems, with an enhanced spectrum of induced P450s and oxidative/post-oxidative reaction rates, are recommended for detecting unknown xenobiotics in genotoxicity studies. PMID- 1903090 TI - Inactivity of acrylonitrile epoxide to modify a Ha-ras DNA in a non-focus transfection-transformation assay. AB - The transforming potential of acrylonitrile epoxide (ANO) was tested in a modified NIH3T3 transfection-transformation assay. This involves a new ras construct obtained by ligating a human c-Ha-ras-1 proto-oncogene to the pSV2neo mammalian vector. The new plasmid was allowed to react with ANO or an established carcinogen in vitro, and the modified ras DNA transfected into NIH 3T3 cells. The transfectants are subjected to triple selections: G418 (neomycin) resistance, low serum growth, and limit dilutions. The end points are scored by cell growth kinetics and monolayer saturation density. In using this protocol, the EJ tumor ras plasmid was the positive control, and anti-benzo[a]pyrene-7,8- dihydrodiol 9,10-epoxide (anti-BPDE) and N-methyl-N-nitrosourea were found to be positive in yielding transformants. Although ANO-modified ras gave rise to two G418R clones, both were scored negative due to their normal growth rate and monolayer density similar to the negative controls. Southern blot analysis of anti-BPDE transformant DNA revealed a fragment of 411 bp, indicating a ras mutation at codon 11 or 12. However, both the ANO clones showed the wild-type band of 355 bp by the same method. PMID- 1903092 TI - Urethan (ethyl carbamate) is an effective promoter of 7,12 dimethylbenz[a]anthracene-induced carcinogenesis in mouse skin two-stage experiments. AB - Groups of hairless mice were painted with urethan alone, with the complete carcinogen 7,12-dimethylbenz[a]anthracene (DMBA) alone, and with an initiating dose of DMBA followed by continual treatment with urethan or with the promoter 12 O-tetradecanoylphorbol-13-acetate (TPA). The animals were examined once a week for an appropriate time period. Malignant and non-malignant skin tumors were registered and classified. Lung adenomas and other internal tumors were also counted. The results show that all types of treatment produced skin tumors, some of which were malignant. When urethan was used lung adenomas also appeared, along with a few other tumors. The results show that a 10% solution of urethan in acetone is a significant promoter, showing synergistic increase of DMBA-induced skin tumors, but urethan is not as strong a promoter as 10 nmol TPA. Urethan is said to be the pure initiator of skin carcinogenesis. Previously the author has shown that urethan alone is a complete carcinogen and here it is shown that it is also a promoter. Hence, the current hypothesis of urethan as a pure initiator in skin carcinogenesis has been disproved. PMID- 1903091 TI - Reductive metabolism and protein binding of chromium(VI) by P450 protein enzymes. AB - The cytochrome P450-dependent reduction of Cr(VI) using reconstituted phospholipid vesicles containing purified preparation of various forms of rabbit and rat liver microsomal cytochrome P450 has been investigated. The alcohol induced form of the rat, P450IIE1, was the most efficient enzyme, 7.2 +/- 0.40 nmol Cr/nmol P450/min, whereas the corresponding rates for rat P450IA1, rat IIB1, rabbit IIB4, rabbit IA2 and rabbit IIE1 were 1.7 +/- 0.09, 2.5 +/- 0.08, 1.6 +/- 0.08, 2.5 +/- 0.15 and 1.6 +/- 0.08 nmol Cr/nmol P450/min respectively. NADPH cytochrome P450 reductase had Cr(VI) reductase activity which was dependent on enzyme concentration. Below 0.15 nmol P450 reductase/ml the sp. act. was low and constant, while at a higher concentration the activity was markedly dependent upon the amount of enzyme present. In a quantitative binding assay it was shown that binding of [51Cr]Cr(VI) to the catalytic enzymes was proportional to the enzyme concentration up to 0.8 nmol P450/ml, which caused binding of 70% of the total radioactivity. Analysis by SDS-PAGE and autoradiography exhibited binding to the individual catalytic proteins of [51Cr]Cr. EDTA treatment removed the radioactivity from the bands matching P450 and P450 reductase, indicating that Cr(III) is bound to the proteins. The reducing activity of both P450 and P450 reductase was potently inhibited by oxygen. The inhibitory effect of oxygen is not due to reoxidation of the reduced Cr and redox cycling. Rat P450IA1 ethoxycoumarin O deethylase activity was inhibited after preincubation with chromate (CrO4(2-). The P450 reductase inhibitor 2'-AMP stimulated the anaerobic P450 reductase dependent Cr(VI) reductase rate approximately 2-fold. Both CO and CCl4 inhibited the different P450 enzymes to various extents. With rabbit P450IIE1 CCl4 stimulated the Cr(VI) reduction approximately 4-fold, whereas the activity of the other enzymes was inhibited when the reconstituted system was incubated with CrO4(2-) and CCl4 prior to NADPH addition. Neither CO nor CCl4 affected the Cr(VI) reducing activity of the P450 reductase. The difference in CrO4(2-) reducing activity of the P450 enzymes and binding to the enzymes may be important for in vivo endoplasmic catalytic metabolism of CrO4(2-). PMID- 1903093 TI - Smokeless tobacco extracts mutate human cells. AB - Two commercial brands of smokeless tobacco were extracted with water and these extracts were tested in human cell mutation assays. Using the human cell line TK 6 which expresses no cytochrome P450, the two extracts tested were found to be detectably mutagenic in the range 1-3 mg/ml extractable solids. In AHH-1 cells which constitutively express cytochrome P450IAI, a similar result was found for both brands tested. The two extracts were treated with neutral nitrite solutions to mimic physiologic oral conditions or acidic conditions or acidic conditions with nitrite to mimic physiologic gastric conditions. The mutagenicity of both extracts for both TK-6 and AHH-1 cells was markedly decreased by treatment at neutral pH with sodium nitrite (0.25 mM) and by acidic treatment (2 h, pH 3.0). Treatment of extracts with sodium nitrite at pH 3.0 did not have any effect on the mutagenicity of the untreated extracts for TK-6 cells. The mutagenicity of both the extracts destroyed by acidic treatment however, seemed to be restored to a level equivalent to the mutagenicity of the untreated extracts for the TK-6 cells. The same series of experiments with P450-proficient AHH-1 cells showed uniform reduction of mutagenic activity. Since the two cell lines are equally sensitive to mutation by aqueous tobacco extracts it is concluded that mutagenicity is not cytochrome P450 mediated. It would further appear that the extract mutagen(s) is acid and neutral nitrite labile. PMID- 1903094 TI - Chemopreventive properties of chlorophyllin: inhibition of aflatoxin B1 (AFB1) DNA binding in vivo and anti-mutagenic activity against AFB1 and two heterocyclic amines in the Salmonella mutagenicity assay. AB - Chlorophyllin (CHL), a sodium/copper derivative of chlorophyll, has been used to treat a number of human conditions with no toxic effects being reported. Recent studies have described the anti-mutagenic activity of CHL in several short-term genotoxicity assays; however, this compound has not been reported to inhibit carcinogen--DNA binding in vivo, and it has yet to be evaluated as an anti carcinogen in any species. The chemopreventive properties of CHL were studied in trout using inhibition of aflatoxin B1 (AFB1)--DNA binding as an end-point. Chlorophyllin and AFB1 were coadministered in the diet, and carcinogen--DNA binding levels were determined in liver after 1, 3, 5 and 7 days. Linear increases in AFB1--DNA binding occurred with time of treatment at each CHL dose level (0, 500, 1000 and 2000 p.p.m.). Each increase in CHL dose produced a concomitant decrease in AFB1--DNA binding, resulting in a series of curves of decreasing slope. At the highest CHL dose level of 2000 p.p.m., AFB1--DNA binding was inhibited by 70%. These results suggest that CHL should be a potent inhibitor of AFB1-induced hepatocarcinogenesis in this model. In the Salmonella assay, CHL exhibited potent anti-mutagenic activity against AFB1 and two heterocyclic amines when incubated in the presence of trout liver activation systems. CHL also inhibited the mutagenic activity of AFB1-8,9-epoxide in the absence of a metabolic activation system. Dietary CHL substantially inhibited liver AFB1-DNA binding in vivo, even when AFB1 was given by i.p. injection to avoid direct AFB1- CHL interaction in the diet or gut. Collectively, these studies support a CHL inhibitory mechanism involving complex formation with the carcinogen in the gut coupled with electrophile scavenging or further complexing in the target organ. PMID- 1903095 TI - Purification and properties of human serum carnosinase. AB - Carnosinase from human plasma was purified 18,000-fold to apparent homogeneity in a four step procedure. The dipeptidase was partially inactivated during DEAE cellulose chromatography; however, it reactivated slowly when concentrated and stored at 4 degrees C. In the second purification step, hydroxylapatite column chromatography, two forms of the enzyme were separated from one another. Human serum carnosinase was found to be a glycoprotein with a pI of 4.4 and a subunit Mr of 75,000; the active enzyme was a dimer, the two subunits being connected by one or more disulfide bonds. The enzyme was especially active in hydrolyzing carnosine and anserine, preferring dipeptides with histidine in the C-terminal position. In most human tissues, the concentration of serum carnosinase was proportional to the percentage of trapped blood in the sample. However, the brain contained about 9 times more enzyme than expected, based on the amount of trapped blood present. The physiological function of this enzyme seems to be the hydrolysis of homocarnosine in the brain and the splitting of carnosine and anserine in the blood stream. Six higher primates were found to have serum carnosinase. Twelve nonprimate mammals were tested; all were lacking the serum enzyme except for the Golden hamster, which had very high concentrations of a carnosinase having somewhat different properties than the higher primate enzyme. PMID- 1903096 TI - Immunoelectron microscopic characterization of lymphocytes containing parallel tubular structures induced by natural but not recombinant interferon-alpha. AB - Activation of natural killer (NK) cell activity is one of the immune functions which can be altered by the interferons (IFNs). We previously incubated healthy donor peripheral blood lymphocytes (PBMC) in the presence of natural (n) IFN alpha and found induction of granular lymphocytes, a proportion of which expressed CD 8 and CD 57. In the present study we further delineated the membrane characteristics of these induced granular lymphocytes and observed the greatest proportion to be CD 16+, with lesser proportions positive for CD 8, CD 57, or coexpressing CD 16 and CD 8. Thus, nIFN-alpha-induced granular lymphocytes have both the morphological and membrane characteristics of functional NK cells. However, in contrast to nIFN-alpha, incubations with recombinant (r) IFN-alpha and n- and rIFN-gamma were found to only enhance NK activity; the concomitant increase in granular lymphocytes as observed after nIFN-alpha incubation was absent. Therefore, even though the different IFNs applied had comparable effects on the function of cytotoxic effector cells, taking into account the observed morphological discrepancy, the unknown mechanisms or pathways by which this is achieved are apparently not identical. PMID- 1903097 TI - Cost effectiveness of tympanic thermometry in the pediatric office setting. AB - This study was designed to see if tympanic thermometry might be more cost effective than cheaper more traditional methods of thermometry when office staff time saved is taken into account. There were 224 patients enrolled from three private pediatric practices. Patients were alternately assigned to have their temperature taken with either a tympanic thermometer or with a rectal or oral thermometer depending on the patient's age. For each child enrolled in the study a nurse was asked to time the temperature taking process. Items included in the cost analysis: a) thermometer costs; b) disposable supply costs; c) personnel costs; d) equipment service costs. The mean duration of temperature taking was 35.2 seconds using tympanic thermometers, 73.4 seconds using electronic predictive thermometers, and 247.2 seconds using glass thermometers. In practices taking an average of 10 temperatures per day, tympanic thermometry saved $2,316/year when compared to glass thermometers and $442/year when compared to electronic predictive thermometers. The data presented in this study show that when nursing time is taken into account, tympanic thermometry is less expensive to perform than traditional methods of thermometry despite the initial higher cost of the thermometer. PMID- 1903098 TI - Genetically determined stereoselective excretion of encainide in humans and electrophysiologic effects of its enantiomers in canine cardiac Purkinje fibers. AB - Encainide metabolism is mediated by the polymorphically distributed cytochrome P450IID6, which displays stereoselectivity for some substrates. In this study we found that urinary recovery during steady-state encainide in three poor metabolizers was high (49% to 80%), consisted mainly of unchanged encainide, was nonstereoselective (+/- ratio, 0.985 to 1.049), and was unchanged by quinidine, a potent inhibitor of P450IID6. In contrast, in seven extensive metabolizers the +/ urinary ratios were 1.20 +/- 0.06 for encainide and 0.81 +/- 0.06 (both p less than 0.01) for the cytochrome P450IID6 products O-desmethylencainide plus 3 methoxy-O-desmethylencainide; with quinidine the total percentage recovery rose from 4% +/- 4% to 37% +/- 9% because of increased recovery of unchanged encainide and became non-stereoselective (+/- ratio, 0.84 +/- 0.08 [encainide alone] versus 0.97 +/- 0.05 [encainide plus quinidine]). In vitro, encainide enantiomers depressed the maximum rate of metabolism with similar frequency and concentration dependence. We conclude that (-)-encainide undergoes preferential metabolism by cytochrome P450IID6; however, this genetically determined stereoselective disposition is unlikely to play a major role in mediating the clinical actions of encainide. PMID- 1903099 TI - Kinetic modeling of in vivo--nuclear magnetic resonance spectroscopy data: 5 fluorouracil in liver and liver tumors. AB - Kinetic modeling has been applied to the time course of the nuclear magnetic resonance signal intensities of 5-fluorouracil and the sum of its catabolites, alpha-fluoro-beta-ureido propanoic acid and alpha-fluoro-beta-alanine, as monitored in liver tumors of seven patients with cancer after brief intraarterial infusion of 5-fluorouracil. Because these data represent only relative tissue concentrations, only ratios of clearance and volume parameters can be estimated (e.g., clearance/central volume of distribution or central volume of distribution/steady-state volume of distribution). On the other hand, parameters that do not refer to volumes, such as half-lives or maximal velocity of metabolic conversion of a nonlinear model, can be estimated in absolute terms. A nonlinear three-compartment model gave satisfactory fits with all of the individual data sets. Kinetics of 5-fluorouracil and catabolites were similar in five patients with metastases of colorectal adenocarcinomas but differed from those of two patients with cholangiocarcinoma and metastases of an anaplastic carcinoma of unknown origin, respectively. PMID- 1903101 TI - Systemic glycoproteinosis resembling Lafora's disease in a cow. AB - A 6-year-old, Hereford/Angus crossbred cow which died acutely was submitted for necropsy and diagnostic evaluation. A toxicity was suspected by the owner who had noticed incoordination of one week's duration. The animal was last observed 24 hours prior to death. Toxicology screens for alkaloids, heavy metals, pesticides and nitrates were negative. The significant histologic abnormalities were confined to the thalamic nuclei, periventricular neurons and the liver. Neurons and hepatocytes contained 1 to 2 intracytoplasmic inclusions which stained faintly eosinophilic to slightly basophilic with H&E. The inclusions frequently had dense central cores and a fibrillar to homogeneous periphery. Based on a battery of histochemical stains for carbohydrates, and other mucosubstances and the morphology and location of the inclusions, a diagnosis of systemic glycoproteinosis consistent with Lafora's disease was made. This case represents the first report of lesions consistent with Lafora's disease in the bovine species. PMID- 1903100 TI - Pharmacokinetics of didanosine in patients with acquired immunodeficiency syndrome or acquired immunodeficiency syndrome-related complex. AB - The pharmacokinetics of didanosine (2',3'-dideoxyinosine) after intravenous and oral administration were evaluated in an open, escalating-dose phase I study in patients with acquired immunodeficiency syndrome (AIDS) or severe AIDS-related complex. Didanosine was administered twice a day for 2 weeks as an intravenous infusion of 60 minutes duration at doses ranging from 0.4 to 16.5 mg/kg, followed by 4 weeks of oral treatment at twice the intravenous dose. Serial blood and urine samples were obtained on the first and final day of intravenous administration and after the first oral dose, as well as at steady state. Didanosine demonstrated linear pharmacokinetic behavior over the dose ranges of 0.4 to 16.5 mg/kg intravenously and 0.8 to 10.2 mg/kg orally. There was no indication of significant changes in pharmacokinetic parameters with repeated administration. The apparent elimination half-life after oral administration was approximately 1.4 hour. Renal clearance values exceeded the glomerular filtration rate, indicating that active tubular secretion of didanosine occurs. Bioavailability of didanosine when administered as a solution with an antacid was approximately 43% for doses from 0.8 to 10.2 mg/kg in patients with AIDS and advanced AIDS-related complex. Bioavailability of didanosine from the citrate phosphate-buffered solution, the formulation currently used in phase II and expanded access studies, was comparable to the formulation used in the phase I trials. PMID- 1903102 TI - Slaving the cytochrome P-450 dependent monooxygenase system by periodically applied light pulses. AB - The light-induced enhancement of 7-ethoxycoumarin-O-deethylase activity was measured in a reconstituted system consisting of the enzyme P-450 II B1 (P-450PB B) and the NADPH-cytochrome P-450 reductase. The phases of the catalytic cycle of 2 x 10(12) protein complexes were locked by periodic application of light pulses (0.1 s duration, 1.2-2.5 s repetition time, and 390-470 nm 0.27 Joule/nmol P 450). More than 80% of the active reconstituted enzyme complexes worked in phase if the repetition time (1.32 s) was slightly smaller than the catalytic cycle time of the free running enzyme (1.54 s). The percentage of synchronized enzyme complexes as a function of the repetition time is shown. It is shown that the lifetime of the product-enzyme complex is shortened by the light. PMID- 1903103 TI - Assessment of exposure to polychlorinated biphenyls: analysis of selected isomers in blood and adipose tissue. AB - Concentrations of 12 selected polychlorinated biphenyl (PCB) congeners and isomers in human serum and adipose tissue after environmental and short- and long term occupational exposures were determined. The individual congener concentrations in adipose tissue varied between less than 0.01 and 420 micrograms/kg (tri-, tetra-, penta-, hexa-, and heptachlorobiphenyls); the dominating isomers were 2,2',4,4',5,5'- and 2,2',3,4,4',5'-hexaCB, which represented approximately 90% of all PCBs in adipose tissue. Those isomers were also the most abundant in serum specimens after environmental exposure, their contribution together with the 2,2',3,4,4',5',6-heptaCB was approximately 90%. After short-term as well as long-term occupational exposure, the most remarkable changes were observed in the concentrations of the tri- and tetrachlorobiphenyls. In long-term occupational exposure 2,4,4'-triCB (mean 3.15 micrograms/liter) and 2,4,4',5-tetraCB (mean, 9.4 micrograms/liter) showed the highest concentrations, whereas after short-term exposure 2,2',5-tri- (mean 2.04 micrograms/liter) and 2,3',4,4'-tetraCB (mean 1.5 micrograms/liter) were most abundant. In people with only environmental exposure, the concentrations in adipose tissue of some PCB isomers were interrelated. The concentrations of the isomers 2,4,4'5-tetraCB (IUPAC 74), 2,2',4,4',5,5'-hexaCB (IUPAC 153), 2,2',3,4,4'5'-hexaCB (IUPAC 138), 2,3,3',4,4',5-hexaCB (IUPAC 156), 2,2',3,4,4',5',6-heptaCB (IUPAC 183), and 2,2',3,3',4,4',5-heptaCB (IUPAC 171) showed close correlation, the coefficients varied from 0.42 to 0.98. The correlation between the concentrations of individual PCB isomers in adipose tissue was highest for 2,4-substituted highly chlorinated isomers, i.e., isomers with longest half-times in the body. PMID- 1903104 TI - Gonadotropin-independent precocious puberty. AB - Gonadotropin-independent precocious puberty presents a challenge in diagnosis and management and in the elucidation of its pathophysiologic basis. Current therapeutic strategies reflect the fact that, irrespective of the underlying mechanism, the clinical and biochemical aspects of the disease process are consequences of gonadal autonomy. In MAS and in testotoxicosis, the most successful therapeutic maneuvers have focused on the local inhibition of steroidogenesis. Despite the positive reports on the use of MPA and cyproterone acetate, long-term experience with these preparations has been generally unsatisfactory, and there is a consensus that testolactone or ketoconazole represent optimal management. Although ketoconazole use, in our experience, has not been associated with any adverse effects either on liver function or on cortisol metabolism, the risk potential is always there. Nevertheless, its effects are dramatic in boys with testotoxicosis, and its mode of action allows for easy monitoring of its efficacy. Testolactone use in MAS, and in combination with spironolactone in testotoxicosis, appears to be relatively safe and reasonably effective. However, because serum testosterone levels are not lowered during treatment, assessment of efficacy depends largely on long-term evaluation of growth rate and of skeletal maturation. The etiology of these disorders remains unclear. The McCune-Albright syndrome is a multisystem disease and sporadic in nature. The organ involvement--ovary, thyroid, adrenal glands, bone, and kidney--is reminiscent of pseudohypoparathyroidism, ironically also bearing Albright's name (Albright's hereditary osteodystrophy, AHO). It is well established that in this syndrome, organ hypofunction associated with the AHO phenotype is caused by deficiency or dysfunction of the G-(or N) regulatory protein essential for production of intracellular cAMP and induction of specific protein kinases. The hypothesis that MAS is caused by abnormal regulation of the membrane receptor/kinase complex would seem logical. Despite its clinical similarity to MAS, the mechanism underlying testostoxicosis is clearly different. This disease is autosomal dominant and is expressed clinically only in boys. Its effects are confined to the production of gonadal autonomy. However, it is difficult to theorize how such autonomy could arise. The enzymatic reactions converting cholesterol to testosterone within the testis or adrenal gland are acquired typically through autosomal recessive inheritance, including the initial rate-limiting step of desmolase side-chain cleavage.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1903106 TI - Two-dimensional 1H, 15N-NMR investigation of uniformly 15N-labeled ribonuclease T1. Complete assignment of 15N resonances. AB - Uniformly 15N-enriched ribonuclease T1 (RNase T1) was obtained from Escherichia coli by recombinant techniques. Heteronuclear 1H, 15N-shift correlation spectra were recorded utilizing proton detection. Direct 1H, 15N connectivities were established applying the heteronuclear multiple-quantum coherence technique. Additional 1H, 1H-TOCSY or 1H, 1H-NOESY transfer steps allowed for sequential assignments. Nitrogen atoms without directly bonded protons were detected by means of the heteronuclear multiple-bond correlation experiment. Signals emerging from 15NH and 15NH2 groups were distinguished by heteronuclear triple-quantum filtering methods. 119 nitrogen resonances out of the expected 127 were assigned unambiguously; in addition, previously obtained proton assignments were extended. Preliminary 1H, 15N NMR investigation were performed on the RNase-T1-3'GMP inhibitor complex. Results were interpreted with respect to nucleotide binding. PMID- 1903107 TI - Signal amplification in HL-60 granulocytes. Evidence that the chemotactic peptide receptor catalytically activates guanine-nucleotide-binding regulatory proteins in native plasma membranes. AB - Receptors for the chemotactic peptide fMet-Leu-Phe (fMet, N-formylmethionine) are present in membranes of myeloid differentiated human leukemia (HL-60) cells and stimulate phospholipase C via a pertussis-toxin-sensitive guanine-nucleotide binding regulatory protein(s) [G-protein(s)]. We have developed methods for the assessment of formyl-peptide-receptor-stimulated binding of radiolabeled guanosine 5'-[gamma-thio]triphosphate ([35S]GTP[S]) to native HL-60 membranes. Agonist stimulation of [35S]GTP[S] association with the membrane was minimal (less than or equal to 20%) when GTP[S] was the sole nucleotide present in the incubation medium. In contrast, receptor activation led to a marked (up to sixfold) stimulation of [35S]GTP[S] binding when GDP or GTP were present in high (greater than 100-fold) excess of [35S]GTP[S]. The increase in [35S]GTP[S] binding caused by the chemotactic agonist was strictly dependent on the presence of Mg2+ and was significantly increased by Na+. Agonist-independent binding of [35S]GTP[S] and the increase due to the chemotactic agonist were markedly attenuated by both pertussis and cholera toxin. Comparison of the number of chemotactic-peptide-sensitive [35S]GTP[S]-binding sites to the number of chemotactic peptide receptors present in HL-60 membranes provided direct evidence that a single formyl-peptide receptor is capable of catalyzing the binding of [35S]GTP[S] to, and thus the activation of, multiple (up to 20) G-proteins in native plasma membranes. PMID- 1903105 TI - Bioactivity of gonadotropins. AB - It is now certain that both gonadotropins, LH and FSH, are synthesized, stored, and released within the circulation, and excreted as heterologous isoforms that can be distinguished by differences in their bioactive to immunoreactive potential and isoform distribution patterns. The bioactivity (which in this article has been defined as the ability of LH to induce T production in rat interstitial cells and FSH to induce E2 production (via aromatase) in rat Sertoli cells in vitro) results from the ability of gonadotropin isoforms to stimulate postreceptor binding functions upstream from G-protein activation and second messenger stimulation. Within the mix of the heterogeneous isoforms, there could be some that alternatively stimulate Gi protein and inhibit function or some that could stimulate G-protein activation for prolonged periods that extend beyond signal-receptor binding. Methods of separation of isoforms are not yet precise or sophisticated enough to distinguish these isoforms. Therefore, the measurement of in vitro bioactivity measures the sum of stimulatory and inhibitory influences on one defined end result. The immunologic potencies also measure the ability of certain selected antibodies to recognize epitopes on gonadotropin molecules, whether they are biologically active or, by virtue of CHO differences or changes in tertiary structure, biologically inactive. Nonetheless, in many instances, the results have been significantly different, with the bioactivity measurements showing greater excursions in stimulatory or inhibitory paradigms than the immunologic potencies. This has been especially true for FSH. Capitalizing on the usefulness of these methodologic advances, we have reviewed the contribution that measurements of gonadotropin bioactivity have made to our understanding of human puberty, which is a continuum in development from conception to adulthood.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1903108 TI - Regulation of hepatic energy metabolism by epidermal growth factor. AB - Employing the non-recirculating perfused rat liver preparation, we have investigated the regulation of hepatic gluconeogenesis, and metabolic fluxes through the tricarboxylic acid cycle and 2-oxoglutarate dehydrogenase reaction by epidermal growth factor (EGF) which mimics the actions of both insulin and Ca(2+) mobilizing hormones (e.g. vasopressin). As monitored by the rate of 14CO2 production from [2-14C]pyruvate (0.5 mM), EGF (10 nM) transiently stimulated the activity of the tricarboxylic acid cycle. EGF also transiently stimulated hepatic gluconeogenesis from pyruvate. The transient stimulation of tricarboxylic acid cycle activity and gluconeogenesis were accompanied by an increase in perfusate Ca2+ content indicating that EGF also altered hepatic Ca2+ fluxes. EGF-elicited stimulation of gluconeogenesis was, at least in part, the result of a transient (50%) inhibition of pyruvate kinase activity. Likewise, EGF-mediated stimulation of tricarboxylic acid cycle activity can, in part, be attributed to EGF-elicited stimulation of metabolic flux through the mitochondrial, Ca(2+)-sensitive, 2 oxoglutarate dehydrogenase reaction. The regulation of hepatic metabolism by EGF appears to be the manifestation of alteration in cellular Ca2+ content since in experiments performed under conditions known to abolish the ability of EGF to alter cytosolic free-Ca2+ concentrations, i.e. in livers of pertussis-toxin treated rats, EGF did not alter either perfusate Ca2+ content or any of the metabolic parameters monitored. Additionally, experiments involving pulsatile infusion of either EGF or phenylephrine into livers demonstrated that, unlike the alpha 1-adrenergic receptor, homologous desensitization of the EGF receptor occurs. Such a homologous desensitization of the EGF receptor can explain the transient nature of EGF-elicited stimulation of various metabolic processes. Since protein kinase C activation by EGF can lead to receptor desensitization, experiments were performed with phorbol esters which either activate or do not alter protein kinase C activity. While the inactive phorbol ester 4 alpha-phorbol 12,13-didecanoate did not modulate the hepatic actions of EGF, activation of protein kinase C by 4 beta-phorbol 12-myristate 13-acetate (70 nM) abolished the ability of EGF to stimulate gluconeogenesis, tricarboxylic acid cycle activity and metabolic flux through the 2-oxoglutarate dehydrogenase complex. PMID- 1903109 TI - Cystic fibrosis presenting with recurrent vomiting and metabolic alkalosis. AB - Between January 1980 and December 1987, ten Saudi Arabian children at Saudi Arabian Oil Co. (Saudi Aramco) health care facilities in the Eastern Province of Saudi Arabia had cystic fibrosis (CF). The incidence of CF in Saudi Arab children less than or equal to 14 years was 1 in 4243. Five of the ten children had hypoelectrolytaemia and metabolic alkalosis on initial presentation. Two of the five had recurrent vomiting, hypoelectrolytaemia and metabolic alkalosis alone and initially no chest symptoms. Early exclusion of CF should be part of the workup in any child, especially in an infant with hypoelectrolytaemia and metabolic alkalosis. PMID- 1903111 TI - The health care delivery system: its impact on patient care. PMID- 1903110 TI - The mode of axonal regeneration of locus coeruleus neurons in the lateral geniculate nucleus following neonatal 6-hydroxydopamine treatment. AB - The effects of neonatal 6-hydroxydopamine (6-OHDA) treatment on the projection of locus coeruleus (LC) neurons to the dorsal part of the lateral geniculate nucleus (dLGN) were examined using histofluorescence and electrophysiological methods. Histofluorescence studies confirmed the previous results of Gustafson and Moore (1987, Dev. Brain Res. 37: 143-155) that catecholamine fibers in the cerebral cortex almost completely disappeared whereas the density of catecholamine fibers in the dLGN increased in the 6-OHDA-treated rats. To quantify the density of the LC projections, we assessed the percentage of LC neurons activated antidromically (projection index, P-index) from the cortex and dLGN. In the 6-OHDA-treated rats, the P-indices for the frontal and visual cortex were greatly reduced, whereas those for the dLGN were increased to twice the control values. In the control rats, about 50% of the LC neurons exhibited antidromic latencies from the dLGN of more than 50 ms, whereas all latencies obtained in the 6-OHDA-treated rats were shorter than 50 ms. These results suggest two types of axonal regeneration of LC neurons: (i) LC neurons projecting to the cerebral cortex lose their distal axonal arborization in the cortex and project alternatively to more proximal sites in the dLGN with regenerating axons; (ii) LC axons projecting to the dLGN with a long trajectory are lost, and regeneration occurs with axons of a shorter trajectory. PMID- 1903112 TI - Cost-effectiveness of routine ultrasound examination in first trimester of pregnancy. AB - The findings of first-trimester ultrasound scans are analyzed. The patients were divided into two groups according to the reliability of their alleged date of last menstrual period and the regularity of their menstrual cycle. The cost effectiveness of a routine first trimester scan as compared to a selective approach is calculated. Based on these data we question the performance of a routine first-trimester scan. PMID- 1903113 TI - Low vs. high osmolar contrast media. PMID- 1903114 TI - Is nuclear medicine cost-effective? AB - Clearly, there is currently no consensus on the cost-effectiveness of nuclear medicine--or in fact any other aspect of medicine. It is hoped that common sense prevails in clinical medicine today. An appropriate case history and physical examination may negate the need for any additional investigation. From the perspective of the capital cost of equipment and supply costs, ultrasound is clearly the most cost-effective diagnostic imaging modality. But while it is useful, it does not always provide definitive answers, and other modalities must be used to arrive at a diagnosis. In comparison, the capital cost of general radiology equipment and nuclear medicine equipment is relatively equal. Radiology has more operating costs per case than nuclear medicine and requires a lower staffing component per given volume of examinations. In any given diagnostic imaging procedure, the practitioner and imagist must maintain a dialogue to ascertain the appropriateness of the study and to use the available resources in the most effective manner. This is even more imperative when CT scanning and MRI are included in the equation. The development of an investigative protocol that makes the most efficient use of the various imaging modalities without compromising the quality of care makes sense for the patient, the physician and the insurance provider. It is unreasonable to expect the physician to be aware of the optimal protocol for the diagnostic workup of every patient. The guidance of the imaging department is required to maximize the efficient use of the available facilities. A critical and exhaustive appraisal of the medical literature may be required to determine the optimal diagnostic protocol.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1903115 TI - Digital videofluorography: a new direction in diagnostic imaging. AB - Accurate information about digital technology is often difficult to obtain because of unrealistic expectations. The development of the digital department is complex and must not be understated. However, we have attempted to show that if a truly committed hospital immediately accepts DVF, this will result in reduced capital and operational costs, as well as lower radiation doses to the patient and operator. We believe this will happen because every major X-ray manufacturer is demonstrating and offering DVF systems, all of which are based on the technology described in this paper. These systems can either be totally integrated into fluoroscopic facilities or be purchased as add-on components to established units. In any event, a modern fluoroscopic facility can cost several hundred thousand dollars, and must last 10 to 15 years. It seems prudent to acquire quality and digital capability so that these units will be adequate in the year 2000 and beyond. PMID- 1903116 TI - Quantitative genetics of postponed aging in Drosophila melanogaster. I. Analysis of outbred populations. AB - Selection has been used to create replicated outbred stocks of Drosophila melanogaster with increased longevity, increased later fecundity, and increased levels of physiological performance at later ages. The present study analyzed the quantitative transmission patterns of such stocks, employing extensive replication in numbers of stocks, individuals, and assayed characters. The populations used derived from five lines with postponed aging and five control lines, all created in 1980 from the same founding base population. The following characters were studied: early 24-hr fecundity, early ovary weight, early female starvation resistance, early male starvation resistance, female longevity and male longevity. Numerous crosses were performed to test for non-Mendelian inheritance, average dominance, maternal effects, sex-linkage and between-line heterogeneity. There was only slight evidence for any of these phenomena arising reproducibly in the characters studied. These findings suggest the value of this set of stocks for studies of the physiological basis of postponed aging. PMID- 1903117 TI - Quantitative genetics of postponed aging in Drosophila melanogaster. II. Analysis of selected lines. AB - Quantitative genetic analyses of Drosophila melanogaster stocks with postponed aging have suffered from the problem of a lack of certainty concerning patterns of allelic differentiation. The present experiments were designed to alleviate this difficulty by selecting for enhanced levels of characters known to be related to postponed aging. Selection successfully increased the degree of differentiation of postponed aging stocks with respect to starvation resistance and fecundity, but persistent additive genetic variance suggested that selection did not result in fixation of alleles. The artificially selected stocks were subjected to crosses to test for patterns of dominance and maternal effects. There was little evidence for these effects in the inheritance of the characters underlying postponed aging, even with the increased differentiation of the selected stocks. PMID- 1903118 TI - Three neighboring genes interact with the Broad-Complex and the Stubble-stubbloid locus to affect imaginal disc morphogenesis in Drosophila. AB - The Broad-Complex (BR-C) is a complex regulatory locus at 2B-5 on the X chromosome of Drosophila melanogaster. The wild-type BR-C products are apparent transcription factors necessary for imaginal disc morphogenesis. Alleles of the Stubble-stubbloid (Sb-sbd) locus at 89B9-10 act as dominant enhancers of broad alleles of the BR-C. Sb-sbd wild-type products are necessary for appendage elongation. We report, here, on three new loci implicated in imaginal disc morphogenesis based on their genetic interactions with both BR-C and/or Sb-sbd mutants. Enhancer of broad (E(br)) was identified as a dominant enhancer of the br1 allele of the BR-C and is a recessive lethal. Mapping of E(br) has led to the identification of two loci, blistered and l(2)B485, mutants of which interact with E(br) and the Sb-sbd locus. Blistered, but not l(2)B485, interacts strongly with the BR-C. Alleles of the blistered locus are viable and disrupt proper wing disc morphogenesis independent of genetic interactions. All three loci map within the 0.6-map unit interval between the genetic markers speck and Irregular facets and to the cytological region 60C5-6; 60E9-10 at the tip of chromosome 2R. Genetic evidence is consistent with the view that the BR-C regulates blistered. PMID- 1903119 TI - Isolation and characterization of the Drosophila retinal degeneration B (rdgB) gene. AB - Retinal degeneration-B (rdgB) mutants of Drosophila melanogaster undergo rapid light-induced retinal degeneration. We conducted a molecular characterization of the rdgB gene to examine the nature of the gene product. Through the isolation and analysis of X-ray-induced rdgB alleles, the cytogenetic position of the gene was determined to be the 12C1 salivary region. Genomic DNA corresponding to this region was isolated by a chromosomal walk. The chromosomal aberrations associated with the three X-ray-induced rdgB alleles were shown to be within a 5-kb genomic region. A single transcription unit was affected by the alleles, identifying it as the rdgB gene. RNA-RNA Northern hybridization indicated the rdgB gene transcribed five mRNAs ranging in size from 3.9 to 9.5 kb. These mRNAs were expressed in adult heads, but not detected in bodies. Analysis of RNA isolated from wild-type and eyes absent heads indicated that rdgB mRNA expression was not restricted to the retina. DNA sequence analysis of the transcription unit revealed an open reading frame capable of encoding a 116-kD transmembrane protein. The deduced protein shows no overall homology to previously described proteins, but has sequences in common with proposed functional domains of Ca(2+) ATPase. PMID- 1903122 TI - A checklist for managing the dementia patient. AB - Primary care physicians seeing a growing number of elderly demented patients must consider a number of problem areas when treating such patients. This article offers the mnemonic FICS'M (Family, Intellectual status, Continence, Sleep, and Mobility) to help physicians address treatable problems associated with dementing illnesses. Strategies are offered to minimize morbidity from the particular problem and from the treatment, such as trying "low toxicity" therapies and medications with few side effects. Other medical, ethical, and legal issues are discussed, including handling dangerous behaviors and abuse, nursing home placement and autopsy, and specific treatment of both the dementia itself and associated disorders--agitation, depression, and delirium. PMID- 1903121 TI - Estimation of gene diversity at the b locus of the constant region of the immunoglobulin light chain in natural populations of European rabbit (Oryctolagus cuniculus) in Portugal, Andalusia and on the Azorean Islands. AB - The minimal gene diversity at a locus of the antibody constant region, as estimated in natural populations of rabbit, revealed levels of heterozygosity similar to those reported for the major histocompatibility complex in human and murine populations. Sera of 416 wild rabbits were collected on the Iberian peninsula and on three islands of the Azorean archipelago and analyzed for the occurrence of the serological markers of the b locus of the immunoglobulin light chain. All four serotypes present in domestic rabbits were found in Portugal. They represented less than 50% of the gene pool. In Andalusia this was less than 15% and on the Azorean islands less than 10%. The pronounced and systematic hierarchy in allele frequencies, previously found in populations from the more recent distribution area of the species, was not observed. On the peninsula, the frequencies of the "domestic" alleles were similar, averaging 10%. The Portuguese sample revealed a total heterozygosity of at least 87%. This high value was supported by at least 11 serologically different alleles, none of them occurring at frequencies above 20%. These data are in agreement with an Iberian origin of the European rabbit and strongly suggest the coalescence of b locus allelic lines drawn from Iberian and western populations. The role of balancing selection in the evolution of the b locus polymorphism was further emphasized. PMID- 1903120 TI - A cluster of vitellogenin genes in the Mediterranean fruit fly Ceratitis capitata: sequence and structural conservation in dipteran yolk proteins and their genes. AB - Four genes encoding the major egg yolk polypeptides of the Mediterranean fruit fly Ceratitis capitata, vitellogenins 1 and 2 (VG1 and VG2), were cloned, characterized and partially sequenced. The genes are located on the same region of chromosome 5 and are organized in pairs, each encoding the two polypeptides on opposite DNA strands. Restriction and nucleotide sequence analysis indicate that the gene pairs have arisen from an ancestral pair by a relatively recent duplication event. The transcribed part is very similar to that of the Drosophila melanogaster yolk protein genes Yp1, Yp2 and Yp3. The Vg1 genes have two introns at the same positions as those in D. melanogaster Yp3; the Vg2 genes have only one of the introns, as do D. melanogaster Yp1 and Yp2. Comparison of the five polypeptide sequences shows extensive homology, with 27% of the residues being invariable. The sequence similarity of the processed proteins extends in two regions separated by a nonconserved region of varying size. Secondary structure predictions suggest a highly conserved secondary structure pattern in the two regions, which probably correspond to structural and functional domains. The carboxy-end domain of the C. capitata proteins shows the same sequence similarities with triacyglycerol lipases that have been reported previously for the D. melanogaster yolk proteins. Analysis of codon usage shows significant differences between D. melanogaster and C. capitata vitellogenins with the latter exhibiting a less biased representation of synonymous codons. PMID- 1903123 TI - Activation of the hepatocarcinogen aflatoxin B1 by forms of human hepatic cytochromes P-450: some do and some don't. PMID- 1903124 TI - Different types of chronic hepatitis in alcoholic patients: does chronic hepatitis induced by alcohol exist? AB - To verify the existence of chronic hepatitis induced by alcohol, the clinicopathological features of chronic hepatitis in heavy drinkers were studied using various viral markers. Histological features of chronic active hepatitis were seen in 27 heavy drinkers. These patients were divided into four groups. The AL group (seven cases) consisted of alcoholics who were negative for both hepatitis C antibody and HBsAg; the HB group (four cases) was positive for HBsAg; the HC1 group (seven cases) was positive for hepatitis C antibody but negative for hepatitis C virus-RNA genome; and the HC2 group (nine cases) was positive both for hepatitis C antibody and hepatitis C virus-RNA genome. Serum AST and ALT activity declined during 4 wk of abstinence in most patients in the AL group and in the HC1 group. The response of serum AST and ALT to abstinence was poor in most patients in the HB group and the HC2 group. Serum desialo-transferrin and alcohol liver membrane antibodies were detected more frequently in the sera of patients in the AL group and HC1 group. A trend toward increased frequency of centrilobular ballooning existed in the AL group, but this did not reach statistical significance. These results suggest that chronic active hepatitis in patients in the AL group, in whom markers of HBV and hepatitis C virus were absent, may be caused by alcohol. Patients in the HC1 group who had hepatitis C antibody but not hepatitis C virus-RNA may represent cases where both alcohol and hepatitis C virus are involved. PMID- 1903125 TI - Alterations in influence of granuloma-derived cytokines on fibrogenesis in the course of murine Schistosoma mansoni infection. AB - Schistosomiasis is the main cause of hepatic fibrosis worldwide, yet its pathogenesis remains unknown. We previously reported that conditioned medium from cultures of hepatic egg granulomas (isolated from mice acutely infected with Schistosoma mansoni) can stimulate fibroblast proliferation and matrix production in vitro. We have proposed that initiation of hepatic fibrosis in this infection might be under the control of granuloma-derived cytokines. We now report that conditioned medium from cultures of schistosomal egg granulomas isolated from liver of chronically infected mice has reduced fibrogenic activity compared with medium from cultures of granulomas obtained from more acutely infected mice. In related studies, we adoptively transferred splenocytes from infected mice and examined the fibrogenic activity in culture supernatants of hepatic egg granulomas isolated from the recipients. Those prepared from recipients of splenocytes from chronically infected mice contained substantially less fibrogenic activity than did those from recipients of splenocytes of acutely infected mice. These findings suggest that the fibrogenic influence of schistosomal egg granuloma products decreases during the course of chronic murine S. mansoni infection. Furthermore, our preliminary findings suggest that immunoregulatory cells may be responsible for the down-regulation of this influence. Previous observations indicating that in murine schistosomiasis hepatic collagen and hyaluronate synthesis and deposition are elevated in acute but not chronic infection might be explained on the basis of our observations. PMID- 1903126 TI - Antecedents and interventions for aggressive behavior of patients at a geropsychiatric state hospital. AB - Aggressive geropsychiatric patients pose major problems for long-term care facilities. Two exploratory surveys at a geropsychiatric state hospital, separated by brief programs of inservice training on managing aggressive patients, examined several aspects of aggressive behavior and staff interventions. Major findings included a stable overall prevalence of aggressive behavior in both survey periods; a persistently higher prevalence of aggression and a higher rate of physical aggression among dementia patients than among other patients; and staff-patient exchanges as a major triggering event for aggression. In the survey period after the inservice training, staff interventions remained similar for nondementia patients; however, for dementia patients, interpersonal interventions were used less frequently, and p.r.n. medications, alone or in combination with seclusion or restraint, were used more often. PMID- 1903127 TI - Using written communication with patient groups to promote behavioral change in chronic mentally ill patients. AB - Patient-managed problem-solving groups have been used in inpatient settings to increase the responsible activity of patients with chronic mental illness. In a study using a repeated measures design, staff prepared written notes describing patients' adherence to programmatic expectations and submitted them to patient managed problem-solving groups, which recommended consequences for patients' behavior. The intervention increased the frequency of targeted behavior compared with the frequency of the behavior during baseline periods. The authors suggest that this procedure may be applied to a variety of behaviors in other treatment settings. PMID- 1903128 TI - [Monitoring of postoperative enteral feeding using the H2 breath test]. AB - A group of 24 patients which underwent extensive abdominal surgery (gastrectomy and esophagus resection) were fed with a chemically defined diet by way of a needle catheter jejunostomy starting on day five postoperatively. On the fourth postoperative day the jejunocaecal transit time was measured by hydrogen breath test with a median of 97.5 min. Under enteral nutrition, hydrogen exhalation showed a significant rise in all patients. The 8 patients who developed diarrhea (33%) had significantly elevated hydrogen exhalation in relationship to the patients with no diarrhea. 6-12 h before diarrhea, patients had a significant increase in their hydrogen exhalation in correlation to the beginning of carbohydrate malabsorption. Therefore, the hydrogen breath test is a simple, non invasive method to evaluate carbohydrate malabsorption and the risk of developing diarrhea under enteral nutrition. PMID- 1903129 TI - [L-tryptophan and the eosinophilia-myalgia syndrome--consequences for artificial nutrition?]. AB - Present knowledge on the possible cause of the tryptophan-induced eosinophilia myalgia syndrome is discussed on the basis of a literature survey. The initially favored hypothesis of metabolites of a deranged tryptophan metabolism in some persons as cause of the syndrome has no plausibility for several reasons discussed in this paper. In the meantime trace backs of implicated tryptophan lots have led to one manufacturer who has changed his production procedure. The implicated lots contain a variety of impurities detectable by HPLC. Whether these impurities are the immediate cause of the syndrome or just markers remains to be established. An animal model suitable to clarify this question has recently been developed. Taking all these measures to identify and eliminate suspicious lots, there is no reason to withhold live saving artificial nutrition with tryptophan containing preparations. PMID- 1903130 TI - Effects of controlled frequency breathing during exercise on blood gases and acid base balance. AB - The purpose of this study was to determine the effect of a reduced ventilatory frequency (Vf) on blood gases and acid-base changes during three intensities of cycling exercise. VO2max and lactate threshold workload (LaT) of six subjects were assessed on a Monark ergometer. Experimental rides were performed 1) with no restriction on Vf (NB) and 2) with a prescribed Vf of 10/min (CFB). Each exercise period consisted of 8 min at 10% of VO2max below the LaT (WI), followed immediately by 8 min at LaT (WII), followed immediately by 8 min at 10% of VO2max above LaT (WIII). Blood was taken from a heated fingertip at the end of each load and analyzed for lactate concentration, pH, PO2, and PCO2. Respiratory exchange was monitored continuously using open circuit indirect calorimetry. Minute ventilation (VE) was significantly reduced by CFB at all three workloads. The reduced VE resulted in lower (p less than 0.05) blood PO2 at each workload (p less than 0.05), however, neither blood lactate nor VO2 were significantly different between CFB and NB for the three loads. Blood [H+] was significantly higher in CFB than NB at all three loads with the greatest difference between trials at WIII (NB: 37.93 +/- 0.68 nM: CFB: 44.77 +/- 1.02 nM). This was accounted for by a significantly higher PCO2 during CFB in WII and WIII (WII, NB: 33.0 +/- 1.4 mmHg, CFB: 35.7 +/- 2.7 mmHg; WIII, NB: 31.2 +/- 1.7 mmHg, CFB: 38.9 +/- 2.4 mmHg).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1903131 TI - [Labyrinthitis ossificans after pneumococcal meningitis]. AB - In labyrinthitis ossificans the membranous labyrinth and the endosteum are obliterated by pathological ossification. The pathogenesis, differential diagnosis and radiological findings of a case of labyrinthitis ossificans caused by pneumococcal meningitis are described. The destructive process in the membranous labyrinth can be shown by radiology. The importance of early diagnosis for rehabilitation of hearing loss after treatment is demonstrated. PMID- 1903132 TI - A DNA primer/probe system for the rapid and sensitive detection of Mycobacterium tuberculosis-complex pathogens. AB - A 1.5 kb EcoRI-BamHI restriction fragment from Mycobacterium tuberculosis was found to hybridize specifically with genomic DNA from M. tuberculosis-complex organisms. Primers were designed from the terminal sequences of this fragment and used to amplify uniquely M. tuberculosis-group DNA in a polymerase chain reaction. It is suggested that a combination of these primers and probe will prove a useful tool for the early diagnosis of tuberculous infections. PMID- 1903133 TI - Effect of growth temperature on virulence of strains of Listeria monocytogenes in the mouse: evidence for a dose dependence. AB - Growth of Listeria monocytogenes at 4 degrees C significantly increased its virulence for mice by the intravenous route and the effect was dose-dependent. Virulence was apparent only at a dose of about or above 10(4) viable listerias. At slightly lower doses of about 10(3), no such effect was observed. Growth at 4 degrees C did not increase the virulence of the strains for mice by oral-gastric challenge when given at doses of approximately 10(10). PMID- 1903135 TI - Survival of Listeria monocytogenes in a food colorant derived from red beets. AB - Three commercial lots of the red beet colorant were inoculated to contain circa 10(3) to 10(7) Listeria monocytogenes strains California, V7, or Scott A per milliliter and stored for 56 d at 7 degrees C. McBride listeria agar was used to determine numbers of survivors. Selected colonies thought to be L. monocytogenes were confirmed biochemically. When necessary, samples were tested by cold enrichment (up to 8 weeks). Samples of colorant initially containing 10(3) to 10(4) strain California/ml were always free of the pathogen after 56 d, and sometimes after 42 d. Samples with high initial numbers (10(5) to 10(6)/ml) were not free of the pathogen after 8 wk at 7 degrees C. Strains V7 and Scott A, regardless of size of initial population, always survived beyond 56 d. Before inoculation, all test samples of colorant were free of L. monocytogenes (direct plating or cold enrichment). PMID- 1903134 TI - Long-term treatment of depression. AB - Because recurrent depression represents a major public health problem, the successful long-term treatment of individuals who develop repeated episodes of depression has become a high clinical priority. Effective preventive treatment requires continued pharmacologic management for most individuals with recurrent depression. Although the efficacy of tricyclic antidepressants or lithium carbonate in preventive treatment has been well established, evidence is less clear for monomaine oxidase inhibitors and the newer antidepressants. In addition to the need for more long-term studies on the new compounds, the role of psychotherapy as combination treatment needs to be further elucidated. PMID- 1903137 TI - Total parenteral nutrition in severe acute pancreatitis. AB - The influence of total parenteral nutrition (TPN) was studied in 67 patients with severe acute pancreatitis having three or more criteria according to Ranson (mean +/- SD = 3.8 +/- 0.21). Although TPN has been reported to not be of benefit in the progress and severity of the disease, we have found that the time TPN is started is important in influencing the course of the disease and in the development of local complications, as well as in the mortality rate. Patients whose TPN was started within the first 72 hours of the disease had a 23.6% complication rate and 13% mortality, in comparison with patients whose TPN was started later in the course of the disease, who had a 95.6% complication rate (p less than 0.01) and a mortality rate of 38% (p less than 0.03). The nutritional status of the patients during TPN administration of 28.4 days was maintained either steady or was improved, as assessed by nitrogen balance, serum levels of transferrin (p less than 0.05), and albumin (p less than 0.05). The administration of fat solution, either to prevent essential fatty acid deficiency or to provide part of the caloric requirements, was found to cause neither clinical nor laboratory worsening of the disease. All pancreatic fistulae that developed during the course of the disease spontaneously closed in patients receiving TPN without operation in a mean period of 33.3 days, and all pseudocysts subsided in an average of 18.3 days. Those who died (overall mortality rate 24%) had had uncontrollable sepsis, which resulted in hypercatabolism and multiple system organ failure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1903136 TI - Influence of nonfermented dairy products containing bacterial starter cultures on lactose maldigestion in humans. AB - The effect of nonfermented dairy products containing yogurt or acidophilus cultures on lactose utilization by lactose-maldigesting humans was investigated. Yogurt and acidophilus milk containing 10(7) or 10(8) of Streptococcus thermophilus and Lactobacillus bulgaricus, or Lactobacillus acidophilus, respectively, were prepared using commercially processed 2% low fat milk. Immediately following inoculation, products were refrigerated. Lactose maldigestion was monitored by measuring breath hydrogen excretion at hourly intervals for 8 h following consumption of 400 ml of each test meal containing approximately 20 g of lactose. The yogurt milk containing 10(8) cfu/ml was shown to contain significant concentrations of microbial beta-galactosidase (EC 3.2.1.23; approximately 3 U/ml), which remained stable for at least 14 d at refrigerator temperatures. Breath hydrogen peaks were delayed and significantly lower (approximately 20 ppm at 5 to 7 h) than control values (approximately 70 ppm at 4 h), and intolerance symptoms were eliminated in all subjects. Yogurt milk containing 10(7) cfu/ml demonstrated intermediate breath hydrogen values and was marginally significantly different from control values. Lactobacillus acidophilus strains with varying resistance to bile and total beta-galactosidase producing potential were also tested. Only one strain, LA-1, which demonstrated low bile resistance and intermediate beta-galactosidase activity, was capable of significantly decreasing breath hydrogen values when 10(8) cfu/ml of milk was consumed. PMID- 1903138 TI - Vasoactive intestinal polypeptide nerve fibers in human and monkey (Macaca fascicularis and Macaca mulatta) kidneys. AB - Nerve fibers immunoreactive for vasoactive intestinal polypeptide (VIP) were demonstrated for the first time by the indirect immunofluorescence technique in human and monkey kidneys. VIP-immunoreactive nerve fibers showing varicosities were observed in the adventitia of arcuate arteries and their branches. The density of VIP-immunoreactive nerve fibers decreased from the juxtamedullary region to the cortex. Occasionally a VIP-immunoreactive varicose nerve fiber was observed near the vascular pole of a glomerulus, but no direct innervation of afferent or efferent arterioles in either monkey or human kidney was found. The distribution of VIP-immunoreactive nerve fibers in the monkey and human kidneys was similar to that reported in other species, with less density. The functional role of VIP in the innervation of the kidney is not known, but various suggestions have been made regarding the possible involvement of VIP on vasodilation of selective intrarenal blood vessels, renin secretion, and/or effects on tubules. While none of these questions were established at this time they would appear to be logical areas for further study. PMID- 1903139 TI - Change in the amount of epsilon-hexosyllysine, UV absorbance, and fluorescence of collagen with age in different animal species. AB - Skin and aorta collagen specimens of Wistar rats, white mice, beagle dogs, cats, horses, and human necropsies of different ages were examined with respect to the content of glycated products. The data presented show that (a) glycation and accumulation of the chromophore(s) are comparable in collagen samples from different species of comparable age; (b) glycation and pigmented accumulation increase markedly during the first 5-10 years of age; (c) the extent of glycation is different in different tissues (in particular, glycation of aortal collagen is about twice that of skin collagen); and (d) collagen pigmentation as followed by fluorescence is comparable in aortal and skin collagen (except below 10 years); pigmentation measured by absorbance at 350 nm is, on the contrary, lower in aortal than in skin collagen. Based on the assumption of constant blood glucose level during the life span, it appears feasible to conclude that the degree of nonenzymatic collagen glycation reflects the time period for which the protein was exposed to the action of sugars. This period, because of increased cross linking, is likely to be extended in older animals. Other factors, such as differences in collagen turnover between different tissues and the intensity of the removal process of the glycated products, should be taken into consideration as well. PMID- 1903140 TI - Food restriction retards age-related biochemical changes in rat small intestine. AB - Previous studies have demonstrated that the specific activities of several proximal small intestinal mucosal enzymes fall in the aging rat. This reduction was due to a delay in the full expression of activity of these enzymes during epithelial cell transit from the crypt onto the intestinal villus. We now show in the ad libitum fed Fischer 344 rat that jejunal sucrase, maltase, and alkaline phosphatase specific activities do not fall gradually throughout the life span, but are reduced during senescence. Caloric restriction to 60% of ad libitum intake (DR) abolishes or delays this fall in enzyme activity. Jejunal mucosal immunoprecipitable sucrase-isomaltase (S-I) content also falls with age, but sucrase specific activity per molecule of S-I is less in the older ad libitum fed (approximately 45) than in the DR rats (approximately 60). Jejunal lactase activity falls gradually throughout the life span of ad libitum and DR rats, but lactase activity consistently was higher in DR animals. These observations indicate that DR alters the age-related changes in the activity of several enzymes in the rapidly replicating gut mucosa. PMID- 1903142 TI - Upregulation of interferon-gamma binding by tumor necrosis factor and lymphotoxin: disparate potencies of the cytokines and modulation of their effects by phorbol ester. AB - Tumor necrosis factor (TNF) and interferon-gamma (IFN-gamma) are immune modulating cytokines that exert synergistic cytotoxic effects in several types of tumor cells, including ASPC-1 human pancreatic carcinoma cells. Lymphotoxin (LT), is a cytokine that binds to the TNF receptor and mimicks most of the biological actions of TNF. In the present study, we examined ASPC-1 cells for cytokine mediated modulation of TNF and IFN-gamma receptors. Treatment of ASPC-1 cells with recombinant human IFN-gamma (rhIFN-gamma) did not significantly alter 125I rhTNF binding. In contrast, treatment with rhTNF led to a dose- and time dependent increase in 125I-rhIFN-gamma binding and internalization. Scatchard analysis revealed that rhTNF increased the number of 125I-rhIFN-gamma binding sites from 11,000 sites/cell to 23,000 sites/cell without altering receptor affinity. Although rhLT also increased 125I-rhIFN-gamma binding, it was 100-fold less potent than rhTNF. In contrast, rhLT was only 10-fold less potent than rhTNF in displacing 125I-rhTNF from its receptor. The phorbol ester 12-O-tetradecanoyl phorbol-13-acetate (TPA) blocked the rhLT- and rhTNF-mediated increase in 125I rhIFN-gamma binding and markedly decreased 125I-rhTNF binding. These data suggest that both TNF and LT upregulate IFN-gamma receptors in ASPC-1 cells, but that LT is much less efficient than TNF. Further, the TPA-induced attenuation of IFN gamma receptor upregulation suggests that protein kinase C activation can regulate the TNF/LT-mediated pathways involved in IFN-gamma receptor upregulation. PMID- 1903141 TI - Interferon-induced modulation of epidermal growth factor-stimulated growth of a human breast tumor cell line. AB - We have determined that interferon-alpha (IFN-alpha) and IFN-gamma inhibit the growth of a human breast tumor cell line, S4, in vitro. Cells were more sensitive to the antiproliferative effects of low-dose IFN-gamma than IFN-alpha. As the growth of the S4 cell line is enhanced by epidermal growth factor (EGF), we examined the effect of IFN on EGF-dependent growth of S4 cells. Cells plated in 2.5% serum alone failed to grow. EGF stimulated these cells to grow more than twofold. IFN substantially attenuated the EGF-stimulated growth of S4 cells. Binding of EGF to its receptor was unaffected by pretreatment of cells with IFN alpha. However, a 24-h exposure of cells to IFN-gamma significantly increased the number of EGF receptors on S4 cells. Internalization of the EGF receptor was unaffected by IFN treatment. Binding remained elevated through 4 days of IFN gamma exposure. Scatchard analysis of receptor binding data revealed that IFN gamma increased the number of binding sites without changing the affinity of the receptor for its ligand. These results demonstrate that IFN inhibits EGF stimulated growth of a breast tumor cell line and suggest that the antiproliferative effect of IFN may be due, in part, to its interaction with growth factor-initiated pathways. PMID- 1903144 TI - Mechanisms responsible for suppression of FSH and LH during lactation in the rat. AB - Mechanisms responsible for suppression of FSH and LH secretion during lactation were investigated in rats, with special reference to the suckling stimulus and ovarian inhibin. Concentrations of immunoreactive inhibin in the peripheral plasma and bioactive inhibin in ovarian venous plasma were always low on days 3 and 5 of lactation in dams nursing eight pups, whereas values were always high on days 17 and 20 of lactation in dams nursing eight pups and on day 5 of lactation in dams nursing two pups. There was an FSH surge within 48 h after removal of litters on days 3 and 5 of lactation in dams nursing eight pups, whereas plasma concentrations of FSH were unchanged within 48 h by removal of litters on days 17 and 20 of lactation in dams nursing eight pups and on day 5 of lactation in dams nursing two pups. Plasma LH concentrations increased significantly compared with those of control animals within 24 h after removal of the litter on any day of lactation, regardless of the litter size. Plasma FSH levels increased within 6 h after bilateral or unilateral ovariectomy in lactating rats only on the days when plasma concentrations of inhibin were high before ovariectomy, such as day 17 of lactation in dams nursing eight pups and on day 5 of lactation in dams nursing two pups, whereas the mean concentrations of plasma LH showed no significant increase within 12 h after bilateral ovariectomy in these lactating rats. Treatment with progesterone or oestradiol-17 beta after unilateral ovariectomy did not inhibit the increase in plasma FSH levels, while the increase in plasma concentrations of FSH after surgery was completely inhibited by injecting inhibin (porcine follicular fluid). Treatment with steroid hormones inhibited the basal levels of LH in unilateral ovariectomized lactating rats. Plasma FSH concentrations increased sharply within 6 h after a single i.v. injection of anti inhibin serum on days 10, 15 and 20 of lactation in dams nursing eight pups and on day 5 of lactation in dams nursing two pups, whereas only a small but significant increase in concentrations of FSH was noted 6 h after the antiserum treatment on day 5 of lactation in dams nursing eight pups. Concentrations of plasma LH were unchanged by treatment with antiserum in lactating rats throughout lactation.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1903143 TI - Proliferative response to seven affinity purified mycobacterial antigens in eight strains of inbred mice. AB - This study compares the T-cell-stimulating ability of different mycobacterial antigens. The responses to crude culture filtrates and seven affinity-purified antigens were investigated in eight strains of inbred mice. Large differences in the stimulating abilities of the antigens were observed, and four antigens were found to give a powerful T-cell stimulation. Some antigens divided the strains into high and low responders, while a 17-kDa antigen was found to be exceedingly T-cell stimulatory in mice of all tested haplotypes. The responses of the eight strains were analyzed by comparing the response patterns of the strains. Using a statistical model based on antigen ranking, five strains were found to have a similar response pattern; three strains were found to differ. These results demonstrate the significance of the choice of mouse strain in studies of mycobacterial immunology and, furthermore, indicate that when research is conducted to develop new mycobacterial vaccines, it is important to include panels of antigens. PMID- 1903145 TI - Autonomous FSH synthesis in vitro in anterior pituitary glands and grafts from female rats. AB - When pituitary glands from intact female, but not from ovariectomized rats, are incubated for 8 h in medium TC199 without further additives, FSH is synthesized. This LHRH-independent (or autonomous) FSH synthesis is prevented when bovine follicular fluid (bFF) is added to the incubation medium. Results from preliminary experiments, however, indicate no clear autonomous FSH synthesis after long-term absence of LHRH. To investigate the regulatory mechanisms involved in autonomous FSH synthesis and release, pituitary glands (exposed to endogenous LHRH) and pituitary grafts (not exposed to endogenous LHRH) from intact and ovariectomized rats were incubated for 8 h in medium TC199. Total FSH content (FSH released plus FSH remaining in the tissue) was compared with that in non-incubated glands or grafts, giving an indication of FSH synthesis. In addition, some of the animals were given LHRH pulses for 40 h before incubation. When pituitary tissue was taken from intact female rats, FSH synthesis occurred in the animals' own glands and in grafts from LHRH-pretreated rats. No FSH synthesis was seen in ovariectomized rats with or without pretreatment with bFF and/or LHRH. However, when ovariectomized rats had been pretreated with oestrogen, FSH synthesis was measured in vitro after pulsatile LHRH treatment in vivo. The results indicate that autonomous FSH synthesis in vitro is dependent upon previous (in vivo) exposure of the glands to both oestrogen and LHRH. PMID- 1903146 TI - Effect of thyroid hormone on the pre- and post-natal development of the rat testis. AB - The relationship between thyroid function and testicular development in the rat was investigated. Hypothyroidism was induced during fetal or post-natal life by adding methimazole (MMI) to the drinking water of pregnant or lactating mothers. A group of newborn rats was treated with MMI and i.p. injections of L-tri iodothyronine (L-T3). Hypothyroidism was shown by the reduced serum levels of total T3 and of total thyroxine (T4) in pregnant mothers and in pubertal rats. Testes were studied using light microscopy at 18 and 21 days post coitum or during puberty (21, 35 and 50 days after birth); serum levels of gonadotrophins were also evaluated in pubertal rats. Hypothyroidism had no effect on testicular development during fetal life and when induced in newborn rats it was associated at puberty with reduced serum levels of FSH and LH and with delayed maturation of the testis compared with control rats. The delay in maturation consisted of a reduction in the diameter of seminiferous tubules, and a reduction in the number of germ cells per tubule; this was associated with increased degeneration and arrested maturation of germ cells. In addition, Sertoli cells demonstrated retarded development, as indicated by a delay in the appearance of cytoplasmic lipids and in the development of a tubule lumen. Hormonal and morphological abnormalities were absent in rats treated with MMI plus L-T3. In conclusion, hypothyroidism occurring soon after birth caused reduced levels of gonadotrophins in the serum and a delay in pubertal spermatogenesis, possibly due to retarded differentiation of the Sertoli cells. PMID- 1903148 TI - Gingival hyperplasia due to sodium valproate. PMID- 1903147 TI - Blood flow reactivity to hypercapnia in strictly unilateral carotid disease: preliminary results. AB - To show relationship between degree of carotid arterial stenosis and cerebral blood flow reactivity (RES%) to induced hypercapnia, fluorine-18-fluoromethane and positron emission tomography (PET) was used to study 18 patients with carotid distribution transient ischaemic attacks (TIA), all free of stroke, who had angiographic-proven unilateral arterial disease. Non-involved carotid arteries were either normal or had non-stenotic plaque. Either normal arteries or nonstenotic ulcerations in the symptomatic carotid arteries were present in five of 18 (28%), ipsilateral carotid stenosis from 50-99% was present in eight of 18 (44%), and ipsilateral internal carotid occlusion was present in five of 18 (28%) patients. In comparison with 14 normal controls, all patients with symptomatic middle cerebral artery (MCA) flow territories had significantly lower mean (SEM) RES% [5.0' (0.2) vs 4.0 (0.9), p less than 0.04]. Symptomatic anterior borderzone (ABZ) RES% was also significantly lower [4.6 (0.4) vs 3.3 (0.9), p less than 0.04], than controls. In patient subgroup comparisons, the 50-99% stenosis subgroup clearly had the lowest MCA RES% [3.4 (0.2)] as well as the lowest ABZ RES% [2.8 (0.4)] on their symptomatic sides. Age, expired pCO2, mean arterial blood pressure, serum glucose, serum haematocrit and number, type and estimated duration of TIAs were not significantly different between subgroups. Linear regression showed a significant relationship between RES% and both measured percentage-stenosis (p = 0.04) and residual luminal diameter (p = 0.05) in symptomatic MCA territories. This approached significance in symptomatic ABZ regions. This preliminary data set suggests that unilateral carotid stenosis can and does result in impaired CO2 reactivity following hypercapnia. The relative normality of CO2 reactivity in those with carotid occlusion is discussed. PMID- 1903149 TI - Cerebrovascular CO2 reactivity in migraine: assessment by transcranial Doppler ultrasound. AB - Cerebrovascular reactivity to CO2 inhalation was studied by transcranial Doppler sonography in 30 patients with classic or common migraine and 39 healthy controls without clinical or ultrasonic signs of arteriosclerosis. Systolic and diastolic Doppler frequencies of the middle cerebral artery were plotted against end-tidal CO2 partial pressure; the reactivity index (I x R) was defined as relative frequency change during a PCO2 increase of 5 mmHg. In the normal subjects, I x R was 20.0 +/- 6.3 for systolic velocities, and 26.0 +/- 8.2 for diastolic values. Migraineurs during their headache-free interval had significantly higher I x R values on the affected side (mean: 41.6 systolic, 61.2 diastolic), compared with either controls (P less than 0.01) or the contralateral side (mean: 28.3 systolic, 30.8 diastolic; P less than 0.01). During the headache attack, CO2 reactivity was significantly lower than normal only for systolic velocities (mean: 8.3; P less than 0.05). Increased CO2 reactivity is thought to be one phenomenon of migraine. Transcranial Doppler CO2 testing of cerebrovascular reactivity is a reliable method that may be of interest for the diagnostic evaluation and management of migraine patients. PMID- 1903151 TI - Watching the numbers: basic data for health care management. AB - Resource utilization is a reasonable first tier measure of the value of health care services received by an employed population. It is generally inversely related to the overall quality of care. Newer time-based measures of efficiency and surveys of customer satisfaction will allow health care organizations to improve efficiency and effectiveness, thereby improving value and moderating cost increases. PMID- 1903150 TI - Using Olmsted County "benchmarks" to assess corporate health care utilization and expenditures. PMID- 1903152 TI - Health maintenance organizations: structure, performance, and current issues for employee health benefits design. AB - After summarizing the origins and key principles of HMOs, including the current characteristics of the HMO industry, this article reviews the evidence of HMO performance in the areas of benefits design, utilization and cost effectiveness, quality of care and consumer satisfaction, and selection and overall employer satisfaction. Outstanding issues and concerns, from the perspective of employee health benefits design, include issues such as assuring a fair price for HMO benefits, employer contribution methods, HMO diversification, and cost escalation and the search for value. Results of research studies have been generally positive about HMO performance on benefits, cost effectiveness, quality, and consumer satisfaction, and more mixed on employer satisfaction. As employers address concerns, some changes are likely in the methods used to integrate HMOs into a health benefits strategy. Because the issues involved in these changes are numerous and complex, careful consideration and design are desirable to assure that the net impact of any change is positive and consistent with overall goals. PMID- 1903153 TI - Benefits facts and figures. PMID- 1903154 TI - Value-managed mental health benefits. AB - The First National Bank of Chicago's comprehensive program for mental health services has been shown to be an effective response to the rising demand and cost of mental health care. By assertively managing a benefit plan rather than capriciously cutting it, employees are afforded quality care while the corporation is able to handle the costs of a worthwhile benefit. The plan represented a collaboration of the Benefits and Medical Units, which brought together philosophies of benefit plan management and research regarding primary prevention and early intervention. Employees are afforded education and early intervention while at the work site and appropriate referrals to cost-efficient providers outside the bank. Should they need time away from the work site for treatment, this along with their reentry is also managed to increase the probability of successful recovery. In this way continuity of care is assured so that recurrent disability (eg, rehospitalization, further STD) may be reduced. The 4-year follow-up investigation of the program reveals management of overall mental health care costs, reduction in inpatient psychiatric hospitalization costs, and reduction in the average length of psychiatric short-term disability episodes for employees. PMID- 1903155 TI - The cost effectiveness of health promotion programs. PMID- 1903157 TI - What's next ..... Rationing? PMID- 1903156 TI - A comprehensive approach to corporate health management. AB - The Northern Telecom Inc. Health, Safety and Environment program is an integrated, cross-functional approach to the management of health and health related risks. We describe the key structural elements of the program and some preliminary data using survey and insurance claims data to follow changes in health-risk factors and diagnosis-specific costs during 5 years of operation of this comprehensive safety, industrial hygiene, primary care, disease prevention, and health promotion program. A pilot study demonstrated significant improvements in risk factors, health service use, and health-related costs. On a company-wide basis, there have been similar changes. We compare these results to published data and discuss possible reasons for the improvements in risks and costs. We conclude that a comprehensive information and skill-building program aimed at management as well as employees and dependents generates synergistic cost beneficial change. PMID- 1903159 TI - An American solution. PMID- 1903158 TI - Acoustic stimulation-induced fetal response compared to traditional nonstress testing. AB - Eighty-eight nonstress tests (NSTs) were obtained on gravid women between 27 and 44 weeks' gestation to compare the results of a three-second acoustic stimulus with a traditional NST. Length of testing time was significantly decreased with the use of acoustic stimulation. Consequently, nursing time and equipment use were also considerably lessened per test. Previous studies indicated that the predictive value of the acoustic stimulation test is comparable or better than the traditional NST. PMID- 1903160 TI - On feeding tubes. PMID- 1903162 TI - Long-term follow-up of brain-damaged children requiring feeding gastrostomy: should an antireflux procedure always be performed? AB - Due to the frequent presence of latent gastroesophageal reflux (GER) in mentally impaired children, it is now standard to perform upper gastrointestinal contrast (UGI) and pH probe studies in all children referred for feeding gastrostomy, even if they are without clinical evidence for GER. For patients with documented GER, an antireflux operation performed in conjunction with gastrostomy is usually considered mandatory. Some authors have suggested that a "protective" antireflux operation be performed at the time of gastrostomy placement in all brain-damaged children, citing a high incidence of postoperative GER in this group of patients following gastrostomy, even with a negative preoperative evaluation for GER. To evaluate this theory, we prospectively studied, over the past 6 years, all mentally retarded children referred for feeding gastrostomy with UGI contrast and esophageal pH probe studies. In total, 148 children were studied; 105 had a positive evaluation for GER and underwent gastrostomy and antireflux surgery. Of the 43 children with a negative preoperative evaluation for GER, 37 are doing well following gastrostomy alone without clinical reflux at an average follow-up of 21 months. Six of the 43 (14%) developed symptomatic GER occurring at an average of 10 months following gastrostomy placement. Five of these children have been successfully treated with an antireflux operation and the sixth patient has been successfully managed nonoperatively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1903161 TI - Drosophila ebony mutants have altered circadian activity rhythms but normal eclosion rhythms. AB - Drosophila ebony mutants exhibit a syndrome of morphological and behavioral phenotypes that include an abnormally dark body color and defects in visual and courtship responses. We now show that mutants carrying any one of five ebony alleles display complex and variable locomotor activity rhythms. Although in the most extreme cases activity is essentially aperiodic, many individuals express short- and/or long-period activity components. Three different ebony mutants (e, e1, and e11) express free-running rhythmicity in a temperature-dependent manner; activity rhythms are robust at 28 degrees C, but weak or absent at 20 degrees C. Even while maintained in a light-dark (LD) cycle, ebony homozygotes characteristically display extremely disorganized patterns of activity; some individuals entrain with an apparently abnormal phase and/or express multiple rhythmic components. Interestingly, the visual system mutation norpA partially suppresses effects of the e1 allele, which suggests that aberrant visual system inputs might contribute to the rhythm deficits of ebony mutants. In contrast to their effects on the locomotor activity rhythm, ebony mutations have no apparent impact on the circadian rhythm of adult eclosion, and thus exert rhythm-specific effects on circadian periodicity. PMID- 1903163 TI - Normal pregnancy outcome after early maternal exposure to gonadotropin releasing hormone agonist. A case report. AB - An infertile woman was treated with leuprolide acetate in preparation for in vitro fertilization and was found to be pregnant after exposure to the gonadotropin releasing hormone agonist (GNRHa) from days 21-38 after her last menstrual period. She delivered a healthy-appearing, male infant at term. We found reports of four other pregnancies with early maternal GNRHa exposure. While no malformations have been reported, patients are advised to use barrier contraception when GNRHa therapy is initiated. PMID- 1903164 TI - Progesterone response to exogenous gonadotropins after suppression with leuprolide acetate in gamete intrafallopian transfer. AB - Fifty-three cycle of ovarian stimulation with human menopausal gonadotropins after suppression of endogenous gonadotropin release with leuprolide acetate were completed for the purpose of performing gamete intrafallopian transfer. Thirty seven biochemical pregnancies resulted, with 29 progressing to clinical status, for rates of 69.8% and 54.7%, respectively, per cycle. In comparing characteristics of the follicular recruitment phases of failed cycles to those of cycles resulting in pregnancies, no differences were observed in serum estradiol concentrations or follicular development. However, pregnancy rates were highly associated with peak concentrations of progesterone prior to the administration of human chorionic gonadotropin. Three levels of progesterone range were found on the basis of outcome: 6 high-progesterone cycles produced no pregnancies (0%), 32 mid-range progesterone cycles produced 31 pregnancies (97%), and 15 low progesterone cycles produced six pregnancies (40%). The pregnancy rate in the last group improved when the luteal support was doubled. PMID- 1903165 TI - Viable pregnancy in a woman with premature ovarian failure treated with gonadotropin suppression and human menopausal gonadotropin stimulation. A case report. AB - Ovulation and pregnancy were achieved in a woman with premature ovarian failure by mildly suppressing the elevated gonadotropins and following with a small dose of human menopausal gonadotropins for completion of follicular maturation. PMID- 1903166 TI - Role of Neisseria gonorrhoeae and Chlamydia trachomatis in intraabdominal abscess formation in the rat. AB - Our concept of the pathogenesis of acute salpingitis and advanced pelvic infection, such as tuboovarian abscess, is evolving. Although Neisseria gonorrhoeae and Chlamydia trachomatis are thought to play a significant role in acute pelvic inflammatory disease, other microorganisms, such as aerobes and anaerobes, have repeatedly been reported to play a significant role, also, particularly in the patient with advanced disease. A study was designed to evaluate the pathogenesis, and particularly any synergistic role, of some aerobes and anaerobes with N gonorrhoeae and C trachomatis abscess formation. Using the rat model developed by Weinstein and Onderdonk, the study demonstrated that N gonorrhoeae and C trachomatis alone do not produce abscesses. However, when combined with facultative or anaerobic bacteria, synergism with abscess formation is noted frequently. The data support the hypothesis that N gonorrhoeae and C trachomatis initiate infection and that aerobic and anaerobic bacteria act synergistically to produce abscesses. In addition, microorganisms not inoculated were found to be recruited into the infectious process. The organisms may gain access to the peritoneal cavity via the lower genital tract or from transmucosal migration from the intestinal flora. PMID- 1903167 TI - Intravenous recombinant tissue-type plasminogen activator (rt-PA) and urokinase (UK) in patients with evolving myocardial infarction--a multicenter double-blind, randomized trial in Japan. AB - Intravenous administrations of 2000 x 10(4)IU (33 mg) (rt-PA2) and 3000 x 10(4)IU (50 mg) (rt-PA3) of a new recombinant tissue plasminogen activator (rt-PA:TD 2061) derived from uterine endothelial cells and urokinase (UK) 96 x 10(4)IU were compared in a double blind, randomized trial of 198 patients with evolving myocardial infarction. All patients entered the trial within 6 h of the onset of symptoms and underwent baseline coronary angiography of the infarct-related coronary artery before thrombolytic therapy was instituted. Sixty minutes following thrombolytic therapy occluded infarct-related arteries were successfully reperfused in 41.5% of 66 patients in the UK, 76.4% of 72 patients in the rt-PA2, and 74.6% of 59 patients in the rt-PA3 group. Statistically significant differences were observed between the UK and rt-PA groups (p less than 0.01). Serum fibrinogen levels declined in all 3 groups at 60 min post therapy by averages of 35.9 +/- 3.1% in the UK, 16.8 +/- 4.8% in the rt-PA2 and 17.5 +/- 4.5% in the rt-PA3 group. The difference between the UK and the rt-PA groups was statistically significant (p less than 0.01). Plasma plasminogen and alpha 2-plasmin inhibitor levels showed the same tendencies. Bleeding was the most commonly observed complication and was most commonly seen at the catheterization site. There was no difference in the incidence among the 3 groups. Hospital deaths occurred in 5.3%, 6.3%, and 4.7% of the cases in the UK, rt-PA2 and rt-PA3 groups, respectively. We conclude, therefore, that rt-PA achieves a significantly higher rate of recanalization with less extensive systemic fibrinogenolysis at the dose employed than does UK. The optimum intravenous dose of rt-PA for Japanese patients is considered to be 2000 x 10(4)IU (33 mg). PMID- 1903168 TI - A case of congenital left ventricular diverticulum with pulmonary stenosis and its scintigraphic characteristics. AB - We encountered a 31-year-old female patient with mild valvular pulmonary stenosis who had no abnormality in the electrocardiogram but pulmonary dilatation in the chest radiograph. Two-dimensional echocardiography and magnetic resonance imaging demonstrated two small protrusions at the interventricular septum indicating diverticula. Large perfusion defects were observed at the anterior wall in the thallium-201 myocardial tomograms. Short axial and vertical long axial images by ECG-gated blood pool tomography revealed an out-pouching best seen during diastole and a good contraction during systole in the corresponding areas. These findings suggested the presence of thin but normal myocardium in the anterior wall, i.e. a muscular type of left ventricular diverticulum. The presence of the muscular type of left ventricular diverticulum at the anterior and septal walls was confirmed by contrast left ventriculography. A congenital diverticulum at the anterior and septal walls with pulmonary stenosis is very rare. Furthermore, its scintigraphic images were quite characteristic and useful for its diagnosis. PMID- 1903169 TI - [A case of autoimmune hepatitis developed by the treatment with interferon]. PMID- 1903170 TI - Hydrated autoclave pretreatment enhances tau immunoreactivity in formalin-fixed normal and Alzheimer's disease brain tissues. AB - We developed a new immunohistochemical method by which normal tau antigenicity can be visualized in paraffin sections of formalin-fixed brain tissue. This method consists of autoclave pretreatment of sections immersed into distilled water (hydrated autoclaving) before incubation with anti-tau antibodies. In normal human brain, immunoreactive tau was detected in neuronal cell bodies and dendrites, axon fibers, astroglia, oligodendroglia and gray matter neuropil. In previous studies on normal tau distribution, different optimized fixations that effectively preserve tau antigenicity were used but none of these revealed all of these compartments together. Our method is therefore considered to be more sensitive for detecting normal tau immunoreactivity. In addition, hydrated autoclaving had an enhancing effect on the abnormally phosphorylated (modified) tau immunoreactivity in formalin-fixed brains. In hydrated autoclaving of sections from patients with Alzheimer's disease, neuropil threads, senile plaques, extracellular and intracellular tangles were enhanced in quantity and in staining intensity. Therefore, modified tau appears to accumulate more densely than expected from conventional immunohistochemistry. Immunoblot analysis showed that normal or modified tau immunoreactivity was totally or partially eliminated on formalin treatment and could be revisualized by hydrated autoclaving, an event presumably related to recovering of formalin-masked tau antigens through denaturation by hydrated autoclaving. PMID- 1903171 TI - Quantitation of nitric oxide formation from nitrovasodilator drugs by chemiluminescence analysis of headspace gas. AB - A rapid and reliable method has been developed for the quantitation of nitric oxide by chemiluminescence analysis of headspace gas. Aqueous nitric oxide standards are used to calibrate the method. There is a linear relationship between the amount of nitric oxide and the redox chemiluminescence detector response over the range of 52-2445 pmol of nitric oxide in 2.0 mL of deionized water contained in a sealed 6.2-mL flask. The intra-day and inter-day coefficient of variation values of the method do not exceed 4% and 9%, respectively. The lower limit of quantitative sensitivity and the lower limit of qualitative detection are 52 pmol and 26 pmol of nitric oxide, respectively. This method has been used to measure nitric oxide formation during the incubation of glyceryl trinitrate or sodium nitroprusside in the presence of cysteine. This method has two major advantages over the currently available procedures for the quantitation of nitric oxide, viz., no artifactual formation of nitric oxide during sample preparation and decreased instrumental contamination. PMID- 1903172 TI - von Willebrand factor: structure and function. AB - Von Willebrand factor (vWF) is an adhesive, multimeric glycoprotein present in plasma, platelets, and subendothelium, which has two main functions: (1) it serves as a carrier for factor VIII and (2) it plays a crucial role in platelet adhesion to subendothelium, acting as a "bridge" between platelet membrane glycoprotein (GP) Ib and GP IIb/IIIa and subendothelial components such as collagen and heparin. vWF is involved at high shear rates in the initial contact of platelets with the subendothelium, in their subsequent spreading, and in thrombus formation. The three pools of vWF (plasma, platelets, and subendothelium) are necessary for optimal adhesion. Specific fragments of vWF involved in binding to platelets, collagen, heparin, and factor VIII have been mapped by using a series of proteases and well-characterized monoclonal antibodies to distinct epitopes of vWF. Several groups, including ours, have identified at least eight functional domains on the 270-kd subunit that consists of 2,050 amino acids. The importance of the binding domains to GP Ib and to collagen is illustrated by the role of vWF fragment SpIII (amino acids 1 through 1,365) in promoting platelet adhesion to collagen. The role of the vWF-GP Ib axis and of the vWF-GP IIb/IIIa axis in platelet-vessel wall interactions has been demonstrated through the study of patients, monoclonal antibodies, recombinant fragments, and synthetic peptides. We have recently expressed fragments of vWF complementary DNA in Escherichia coli. One of these recombinant fragments, which spans amino acids 449 through 730, binds to platelets in the presence of ristocetin, to collagen, and to heparin and has the property of inhibiting ristocetin-induced platelet agglutination. The second fragment, which spans amino acids 914 through 1,364, binds to collagen.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1903173 TI - The association of factor VIII with von Willebrand factor. AB - Factor VIII (FVIII) and von Willebrand factor (vWF) are plasma glycoproteins that circulate as a tightly associated complex. Because they tend to copurify during procedures designed to isolate the biologic activities associated with them, their identity as distinct entities became unequivocally established only during the past 10 years. Improved procedures for the isolation of FVIII, the deduction of the amino acid sequences of FVIII and vWF by using molecular cloning techniques and by direct sequencing, and the use of a variety of biophysical and immunochemical techniques have enhanced the understanding of the FVIII-vWF association. Each subunit of multimeric vWF potentially can bind a single heterodimeric FVIII molecule, although in vivo most of these binding sites are empty. The binding of FVIII to vWF is primarily, if not exclusively, mediated by the light chain of FVIII to the amino-terminal region of the vWF subunit. Cleavage of a fragment from the amino-terminal region of the FVIII light chain by thrombin results in rapid dissociation of the FVIII-vWF complex, a process that apparently is necessary for development of procoagulant activity. Whether this cleavage is needed for the activation of FVIII in the absence of vWF is controversial. The extracellular association of FVIII with vWF may be necessary for efficient secretion of FVIII from its cell of origin. The thermodynamics, kinetics, and nature of the molecular contacts involved in the interaction have not been studied. The association of FVIII with vWF prolongs the lifetime of FVIII in plasma. Whether the FVIII-vWF interaction has other functional roles, such as restricting the location of procoagulant activity, remains unknown. PMID- 1903174 TI - Tolerance of gastric mucosal flap to postoperative irradiation. AB - When malignant lesions of the oral cavity, base of tongue, and oropharynx are treated with radical resection, adequate reconstruction is required. The free gastric mucosal flap with microvascular transfer is being used with increasing frequency at Washington University Medical Center. Because of the advanced nature of the primary lesions, most patients also require postoperative radiation therapy. In this paper the tolerance of the gastric mucosal flap to postoperative radiation therapy is reviewed. The changes resulting from radiation therapy in the mucosal flap were found to be acceptable, and no major complications were encountered. PMID- 1903175 TI - Mayo's medical ventures. PMID- 1903176 TI - [Controlled immunoglobulin therapy in immune hemolytic anemia by positive pool immunoglobulin fluorescence test]. AB - An Italian boy with homozygous beta-thalassemia showed a shortening of transfusion intervals at the age of three years. He had a positive direct antiglobulin test (DAT) because of C3d-loaded red blood cells without any detectable erythrocytic antibody. Serologic investigations indicated a recent EBV infection. Pool immunoglobulin fluorescence test (PIT) revealed a loading of red blood cell membranes with antigens. Oral prednisone therapy did not show any effect. After a single infusion of 400 mg immunoglobulin per kg body weight decrease of hemoglobin concentration slowed down to the rate before crisis. DAT and PIT became negative. The immune hemolytic crisis was possibly due to erythrocyte loading with EBV antigen that caused activation of the alternate complement pathway. Detection of antigen loaded red blood cells by PIT suggested a immunoglobulin therapy in order to coat the structures promoting hemolysis. Thus, a positive PIT seems to be a criterion for successful application of immunoglobulins in immune hemolytic anemia. PMID- 1903178 TI - [Transduction of Bacillus anthracis by phage Tg13ant]. PMID- 1903177 TI - [Expression of the glow worm luciferase gene in mammalian cells using vectors based on vaccinia viruses]. AB - The transient expression of the two reporter genes, the genes for luciferase and bacterial beta-galactosidase, were used for comparative estimation of vaccinia viral promoters and for characterizing of the constructed plasmids. The recombinant clones of vaccinia virus expressing simultaneously and with high efficiency the luciferase and beta-galactosidase were used for studying the reproduction of vaccinia virus in mammalian cells. The advantages of the luciferase gene in using it as a reporter gene are discussed. PMID- 1903179 TI - [The effect of silicon metabolism on genetic transformation in Bacillus subtilis]. AB - Germanium dioxide is found to increase the frequencies of the genetical transformation in Bacillus subtilis 30-40 fold. The increased frequency of transformation was registered in Sil- mutant in contrast to Sil+ strain having the decreased one. Bacillus megatherium strain KU-2 and Bacillus oligonitrophilus KU-1 were isolated from soil. These strains possess better ability to utilize the orthoclase and biotite. Germanium dioxide did not induce the transformation frequencies increase in these strains. Sil mutant of Bacillus oligonitrophilus demonstrated no competence to transformation. PMID- 1903180 TI - Mathematics. Circularly covering clathrin. PMID- 1903181 TI - Ha-Ras augments c-Jun activity and stimulates phosphorylation of its activation domain. AB - Ha-Ras augments c-Jun-mediated transactivation by potentiating the activity of the c-Jun activation domain. Ha-Ras also causes a corresponding increase in phosphorylation of specific sites in that part of the c-Jun protein. A Ha-Ras induced protein kinase cascade resulting in hyperphosphorylation of the c-Jun activation domain could explain how these oncoproteins cooperate to transform rat embryo fibroblasts. PMID- 1903182 TI - Clonal deletion of immature CD4+8+ thymocytes in suspension culture by extrathymic antigen-presenting cells. AB - One mechanism ensuring self tolerance of T cells is the clonal deletion of thymocytes bearing alpha beta T-cell receptors. The stage of thymocyte development at which the interaction with antigen-presenting cells (APCs) leads to deletion, however, has not been determined directly. Indirect evidence suggests that intrathymic APCs induce deletion of CD4+8+ thymocytes (which die by apoptosis) but deletion at less and more mature developmental stages has also been implied. It is also not clear if clonal elimination of thymocytes can be triggered by peripheral antigens carried on extrathymic APCs migrating through the thymus. Here we show antigen-specific induction of apoptosis in CD4+8+ thymocytes cultured in suspension, by thymic as well as splenic APCs. Thus the recognition of antigen by CD4+8+ thymocytes may lead to deletion, suggesting that this is the central mechanism of tolerance induction, which is not limited by the antigen-presenting ability of the thymic stroma. PMID- 1903183 TI - Uptake of Pneumocystis carinii mediated by the macrophage mannose receptor. AB - Human exposure to Pneumocystis carinii is common but, in the absence of acquired or genetic dysfunction of either cellular or humoral immunity, exposure rarely leads to illness. Although alveolar macrophages can degrade P. carinii, macrophage receptors involved in P. carinii recognition have not been clearly defined. Characterization of a predominant surface glycoprotein of the high mannose type led us to investigate the role of the macrophage mannose receptor in this process. We report here that binding and uptake of cultured rat P. carinii by human and rat alveolar macrophages is reduced by 90% in the presence of competitive inhibitors of mannose receptor activity and by adherence of alveolar macrophages to mannan-coated surfaces. Further, only those COS cells transfected with the human macrophage mannose receptor complementary DNA that express surface mannose receptors bind and ingest P. carinii. These studies establish that the macrophage mannose receptor is sufficient for uptake of P. carinii and emphasize the role of the alveolar macrophage in first-line host defence against P. carinii. PMID- 1903184 TI - Dependence of Ypt1 and Sec4 membrane attachment on Bet2. AB - Many small GTP-binding proteins are synthesized as soluble proteins that are post translationally modified as a prerequisite for membrane attachment. Ypt1 and Sec4 are homologous Raslike GTP-binding proteins that have been proposed to regulate the specificity of vesicular traffic at different stages of the secretory pathway by cycling on and off membranes. Here we show that BET2, initially identified as a gene required for transport from endoplasmic reticulum to Golgi apparatus in yeast, encodes a factor that is needed for the membrane attachment of Ypt1 and Sec4. DNA sequence analysis has revealed that Bet2 is homologous to Dpr1 (Ram1), an essential component of a protein prenyltransferase that modifies Ras, enabling it to attach to membranes. We propose that Bet2 modifies Ypt1 and Sec4 in an analogous manner. PMID- 1903185 TI - Silver Spring monkeys. PMID- 1903186 TI - Inhibition of the muscarinic receptor-activated K+ current by N-ethylmaleimide in rabbit heart. AB - The effects of N-ethylmaleimide (NEM), a sulfhydryl alkylating agent, on the ACh activated K+ current were examined in single cells from rabbit hearts using whole cell and single channel patch clamp techniques. Bath application of NEM (50 microM) or the muscarinic antagonist, atropine (1 microM) completely inhibited the ACh-activated K+ current in whole-cell recordings. In cell-attached patch conditions, the inhibitory effect of NEM was still observed; in contrast, atropine was ineffective when the agents were bath applied, indicating that the site of action of NEM is different from that of atropine. Inside-out patch recordings confirmed that GTP was required on the internal side of the membrane for activation of this K+ channel when ACh was present in the pipette. NEM abolished this GTP-activated K+ channel activity. GTP gamma S, a non-hydrolysable GTP analogue, was able to activate this K+ channel in the absence of a muscarinic agonist, an effect thought to be due to the direct activation of GTP-binding proteins. Pretreatment with NEM almost completely prevented this effect of GTP gamma S. In contrast, after the activation of the K+ channel by GTP gamma S had reached a steady-state, NEM failed to show a significant inhibitory effect. These results demonstrate that NEM prevents the activation of muscarinic receptor regulated K+ channel and suggest an involvement of alkylation of the GTP-binding proteins which are coupled to this type of K+ channel. PMID- 1903187 TI - Role of extra- and intracellular calcium in the contractile action of agonists in the guinea-pig ileum. AB - The effects of Ca2(+)-channel blockers (nifedipine and verapamil), EGTA, caffeine or the removal of external Ca2+ on the contractile action of different agonists and transmural electrical stimulation were examined in isolated segments of the proximal and terminal part of the guinea-pig ileum. The effects of agonists and nerve stimulation on membrane potential were also studied by means of the sucrose gap method. Acetylcholine-elicited contractions in both parts and noradrenaline- as well as histamine-induced contractions in the terminal part of the ileum were composed of an initial phasic and a sustained tonic component. Single pulse transmural nerve stimulation elicited smooth muscle twitches, whereas addition of CaCl2 to the tissue bath containing Ca2(+)-free and high-K+ medium elicited a sustained contraction. Both verapamil and nifedipine were more potent in inhibiting the tonic phase of the responses to the agonists or CaCl2 than inhibiting the phasic contractions elicited by transmural nerve stimulation, acetylcholine or noradrenaline. The excitatory junction potentials (e.j.p.s.) as well as smooth muscle twitches were reduced only by high nifedipine concentrations. The effects of acetylcholine on membrane potential and input membrane resistance were affected minimally by the omission of extracellular Ca2+, while the contractions gradually disappeared on repetitive agonist application in the absence of external Ca2+ and were blocked by caffeine preexposure. In Ca2(+)-free solution noradrenaline and histamine partially reduced each other's motor effect, while neither of them changed the contractile action of acetylcholine, yet the contraction induced by noradrenaline was prevented and that of histamine significantly reduced by preexposure to acetylcholine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1903189 TI - Patient care automation: the future is now. Part 6. Does reality live up to the promise? AB - By almost any measure, it appears that patient-centered integrated information systems with an operations optimization focus contribute significantly to an institution's efficiency, efficacy, and quality. As with any other management enhancement tool, savings will only accrue if the institution manages to the savings. Nevertheless, such savings appear realizable and achievable. User communities, including nurses, physicians, administrators, and others all profit individually and collectively by using such a system. Finally, by providing better quality care and spending less time on clerical work, patients are the ultimate recipients of the benefits of an integrated patient-centered approach. PMID- 1903188 TI - Phosphate and thiophosphate group donating adenine and guanine nucleotides inhibit glibenclamide binding to membranes from pancreatic islets. AB - In microsomes obtained from mouse pancreatic islets, the Mg complex of adenosine 5'-triphosphate (MgATP) increased the dissociation constant (KD) for binding of [3H]glibenclamide by sixfold. In the presence of Mg2+, not only ATP but also adenosine 5'-0-(3-thiotriphosphate) (ATP gamma S), adenosine 5'-diphosphate (ADP), guanosine 5'-triphosphate (GTP), guanosine 5'-diphosphate (GDP), guanosine 5'-0-(3-thiotriphosphate) (GTP gamma S) and guanosine 5'-0-(2-thiodiphosphate) (GDP beta S) inhibited binding of [3H]glibenclamide. These effects were not observed in the absence of Mg2+. Half maximally effective concentrations of the Mg complexes of ATP, ADP, ATP gamma S and GDP were 11.6, 19.0, 62.3 and 90.1 mumol/l, respectively. The non-hydrolyzable analogues adenosine 5'-(beta,gamma imidotriphosphate) (AMP-PNP) and guanosine 5'-(beta,gamma-imidotriphosphate) (GMP PNP) did not alter [3H]glibenclamide binding in the presence of Mg2+, MgADP acted much more slowly than MgATP and both MgADP and MgGDP did not inhibit [3H]glibenclamide binding when the concentrations of MgATP and MgGTP were kept low by the hexokinase reaction. Development of MgATP-induced inhibition of [3H]glibenclamide binding and dissociation of [3H]glibenclamide binding occurred at similar rates. However, the reversal of MgATP-induced inhibition of [3H]glibenclamide binding was slower than the association of [3H]glibenclamide with its binding site. Exogenous alkaline phosphatase accelerated the reversal of MgATP-induced inhibition of [3H]glibenclamide binding. MgATP enhanced displacement of [3H]glibenclamide binding by diazoxide. The data suggest that sulfonylureas and diazoxide exert their effects by interaction with the same binding site at the sulfonylurea receptor and that protein phosphorylation modulates the affinity of the receptor. PMID- 1903190 TI - Neurochemical and behavioral effects of acute and chronic treatment with apomorphine in rats. AB - In three experiments, rats were injected once daily with 5.0 mg/kg apomorphine or vehicle and tested for locomotor activity for 10-14 days. In each experiment, apomorphine produced behavioral sensitization, characterized by a progressively greater increase in locomotor activity with each succeeding injection. On day 11 of testing, in an experiment designed to assess the synthesis of dopamine (DA), rats were injected with 5.0 mg/kg apomorphine or vehicle, followed by 100 mg/kg NSD-1015, an inhibitor of the enzyme l-aromatic amino acid decarboxylase. After administration of NSD-1015, concentrations of dihydroxyphenylalanine (DOPA) were determined in striatal and mesolimbic tissues by high performance liquid chromatography (HPLC) with electrochemical detection. The results revealed a significant decrease in accumulation of DOPA in both striatal and mesolimbic tissue after acute treatment with apomorphine. More important, chronic treatment with apomorphine produced a significant increase in accumulation of DOPA in both areas. In subsequent experiments, rats on day 14 of testing were sacrificed for determination of levels of DA, 3,4-dihydroxyphenylacetic acid (DOPAC) or specific binding of [3H]spiperone in the striatum and mesolimbic region. Although levels of DOPAC were significantly reduced in the regions of the brain after an acute injection of apomorphine, chronic treatment with apomorphine did not significantly affect levels of DA, DOPAC or specific binding of [3H]spiperone. These findings suggest that the development of behavioral sensitization to apomorphine may be related to an alteration in the synthesis of DA. PMID- 1903191 TI - Antiphospholipid antibodies and recurrent abortion. AB - We examined the association between anticardiolipin antibodies, lupus anticoagulant, and the risk of recurrent spontaneous abortion in a case-control study conducted in a network of general and teaching hospitals in northern Italy. Subjects consisted of 220 women with two or more unexplained consecutive spontaneous abortions and 193 controls admitted for acute conditions other than immunologic, infective, gynecologic, or cardiovascular. Lupus anticoagulant was detected in 16 of 220 cases (7%, 95% confidence interval 4-11%) but in none of the 193 controls (Fisher exact test, P less than .001). Increased anticardiolipin antibody levels were demonstrated in 19 of 99 cases (19%, 95% confidence interval 12-31%) (seven immunoglobulin (Ig) G, eight IgM, and four IgG and IgM) and in four (all IgG) of 157 controls (3%) for whom data were available. These results offer quantitative evidence on the association between antiphospholipid antibodies and recurrent abortion. PMID- 1903192 TI - Protective effect of intrauterine release of levonorgestrel on pelvic infection: three years' comparative experience of levonorgestrel- and copper-releasing intrauterine devices. PMID- 1903193 TI - Post-translational modifications of the C-terminal region of the rho protein are important for its interaction with membranes and the stimulatory and inhibitory GDP/GTP exchange proteins. AB - We have recently found, by use of the rhoA p21 purified from bovine aortic smooth muscle, that it is similarly post-translationally processed as described for ras p21s: it is first geranylgeranylated at the cysteine residue in the C-terminal region followed by removal of the three C-terminal amino acids and the subsequent carboxyl methylation of the revealed C-terminal cysteine residue. In the present study, we investigated the function(s) of these post-translational modifications of the C-terminal region of rhoA p21 by use of the rhoA p21s purified from bovine aortic smooth muscle and rhoA p21-overexpressing Escherichia coli since the bacterial protein was not modified with a geranylgeranyl moiety. Bovine rhoA p21 bound to plasma membranes and phosphatidylserine-linked Affigel, but bacterial rhoA p21 did not bind to them. The inhibitory GDP/GTP exchange protein for rhoA p21, named GDP dissociation inhibitor (GDI), made a complex with the GDP-bound form of bovine rhoA p21 and thereby inhibited the dissociation of GDP from and the subsequent binding of GTP to it. However, rho GDI neither made a complex with the GDP-bound form of bacterial rhoA p21 nor affected these reactions of the bacterial protein. The stimulatory GDP/GTP exchange protein for rhoA p21, named GDP dissociation stimulator (GDS), stimulated the dissociation of GDP from bovine rhoA p21, but was inactive for the bacterial protein. In contrast, the GTPase activating protein for rhoA p21 is active not only for bovine rhoA p21 but also for the bacterial protein. These results suggest that the post-translational modifications of the C-terminal region of bovine rhoA p21, most presumably the geranylgeranylation, which are absent in bacterial rhoA p21, play important roles in its interaction with membranes and the stimulatory and inhibitory GDP/GTP exchange proteins but not with the GAP. PMID- 1903194 TI - Structure and function of human jun-D. AB - A jun related cDNA and its corresponding genomic fragment were cloned from human cells and sequenced. Polymerase chain reaction analysis showed that this gene is the human homologue of the mouse jun-D gene despite the fact that the degree of amino acid sequence conservation between the two is much poorer (77.3%) than that found between the homologues of c-jun and jun-B (95-98%). The product of this gene binds an AP-1 site and upon cotransfection stimulates the activity of a promoter that bears an AP-1 site. The level of activation is comparable to that of v-jun and the activity of both is further stimulated by v-fos. Deletion mutants of the gene that lack the best conserved region in the activating domain are poorly active. However, our data suggest that the activating domain is not confined exclusively to the conserved regions. Interestingly, at high concentrations human jun-D displays decreased activity which cannot be explained by a simple self squelching model. PMID- 1903195 TI - fosB is a transforming gene encoding a transcriptional activator. AB - The fosB gene encodes a nuclear protein that shows a high degree of homology with c-Fos in several of the known functionally crucial domains, e.g., the leucine zipper and the DNA-binding site, but shows considerable divergence in other regions. Here, we report that FosB, when placed under the control of a constitutive promoter, exhibits clear transforming properties in focus assays using mouse NIH3T3 or rat 208F fibroblasts. The transforming potential of FosB is considerably stronger than that of a corresponding c-fos construct and resembles that of viral fos genes. Using chimeric fos/fosB constructs we show that the C terminal half of FosB is responsible for these stronger transforming properties, apparently by giving rise to significantly higher levels of protein as compared with the corresponding c-fos sequence. Surprisingly, substitution of the N terminus of Fos with that of FosB decreases its transforming potential. These differences in the transforming potential are not related to DNA or protein expression, but rather seem to reflect differences in the molecular function(s) encoded in the N-terminal halves of Fos and FosB protein. Both, fosB- and v-fos transformed cells show increased expression of a number of endogenous genes, including c-jun, transin, alpha 1(III) collagen and tissue plasminogen activator. Transactivation by FosB and v-fos of the c-jun and alpha 1(III) collagen gene promoters and of a 3 x TRE-tk chimeric promoter could be shown in transient CAT assays. v-Fos, but not FosB-transformed cells, also show elevated levels of urokinase and plasminogen activator inhibitor mRNAs, pointing to potential differences in the gene regulatory properties of the two Fos family members. PMID- 1903196 TI - Transfected mouse c-jun can inhibit transformation of primary rat embryo fibroblasts. AB - The c-jun gene, which encodes a transcriptional regulatory protein, is the cellular homologue of the transforming gene of avian sarcoma virus 17. In an attempt to assess the biological activities of mouse c-jun, we studied the consequences of its overproduction in an in vitro transformation assay. A c-jun expression plasmid failed to cooperate with either ras, myc or mutant p53 in this focus formation assay. On the other hand, it dramatically inhibited the ability of various oncogene combinations to elicit foci upon transfection into primary rat embryo fibroblasts. Deletion plasmids lacking either the transactivating domain or the leucine repeat of c-jun still displayed a pronounced inhibitory activity. On the contrary, a plasmid encoding only the first 187 amino acids of c jun had no such activity. The data suggests that enhanced c-jun expression may interfere with the induction or proliferation of transformed cells in this system, and that the inhibitory activity resides in the C-terminal half of the molecule. PMID- 1903197 TI - gsp mutations in human thyroid tumours. AB - The presence of gsp mutations at codons 201 and 227 in the gene coding for the alpha subunit of the GTP-binding Gs protein which stimulates adenylyl cyclase (AC) has been investigated in 31 samples of differentiated thyroid tumours, which had been previously characterized with respect to their adenylyl cyclase activity (ACA) before and after stimulation by thyroid-stimulating hormone (TSH). Polymerase chain reaction (PCR) amplification of DNA extracted from these tumours, followed by high stringency oligonucleotide probing, enabled the detection of mutations in three samples originating from tumours with high constitutive ACA, which was not significantly further stimulated by TSH. Two mutations were at codon 227 and replaced Gln227 by His or Lys, and one was at codon 201, with the substitution of Arg201 by Ser. Because thyrocytes belong to the subset of differentiated cells which are programmed to proliferate in response to elevated cAMP levels, the gsp mutations observed in some differentiated thyroid carcinomas probably contributed to their tumorigenic phenotype. PMID- 1903198 TI - Delivery of aerosolized medication to intubated babies. AB - We studied the delivery of aerosolized cromolyn sodium to intubated babies, and evaluated the effect of changes in delivery techniques. In addition, we compared these results with an in vitro model of aerosol delivery. Cromolyn sodium was used as a marker because once the drug is absorbed, it is excreted unchanged, approximately 50% in urine and 50% in bile. We demonstrated that, in vitro, a conventional, jet-type nebulizer aerosolized 20.5% of a test dose of cromolyn, and only 5.5% of the dose was recovered after passage through 60 cm of ventilator tubing and an endotracheal tube adapter. This increased to 44.5% nebulized and 19% recovered when the volume nebulized was increased from 2 mL to 5 mL. A submicronic nebulizer aerosolized 40% and delivered 33.5% of the test dose. A 20 mg dose of nebulized cromolyn sodium was used as a test dose in infants, after which urine was collected for 4 hours. Forty-three urine samples were collected, after the delivery of cromolyn test doses, from nine babies (16-128 days old) intubated for bronchopulmonary dysplasia. Both the jet and submicronic nebulizers were tested in two positions: 1) in place of the ventilator humidifier, and 2) at the endotracheal tube adapter. There were no statistically significant differences in cromolyn delivery for any system configuration. In all situations, means of less than 0.1% of the test dose were recovered in the urine. We estimated that in all cases, less than 1% of the test dose (approximately 50-100 micrograms of cromolyn) had been deposited in the lung. These results show that although the submicronic nebulizer aerosolized cromolyn more efficiently, no additional cromolyn could be detected in infants. We speculate that a significant portion of the smaller particles are exhaled. PMID- 1903199 TI - Respiratory tract colonization with Pseudomonas aeruginosa in cystic fibrosis: correlations between anti-Pseudomonas aeruginosa antibody levels and pulmonary function. AB - Chronic Pseudomonas aeruginosa respiratory tract colonization in patients with cystic fibrosis is associated with development of antibodies to the organism. In contrast to the protection usually afforded by humoral immunity to a bacterial pathogen, the immune response to P. aeruginosa may help perpetuate infection and contribute to pulmonary damage in cystic fibrosis. To determine if specific anti P. aeruginosa antibody levels correlated with pulmonary dysfunction, we measured antibodies to seven P. aeruginosa serotypes, and correlated the geometric mean titer with pulmonary function tests. Patients were divided into groups without P. aeruginosa colonization (n = 20), with recent colonization (n = 20), and with chronic colonization (n = 60). Noncolonized patients had normal pulmonary function or mild obstructive lung disease, and low anti-P. aeruginosa titers. Pulmonary function tests in recently colonized patients were not different from those of noncolonized patients, but antibody titers were higher. Following colonization FEV1 declined and titers increased rapidly. Patients with chronic colonization had worse pulmonary function and higher titers, but while the former were stable the latter gradually increased. An inverse correlation was found between anti-P. aeruginosa titer and FVC, FEV1, and FEF25-75 (P less than 0.001) in these patients; age was not a factor. The strong correlation between severity of lung disease and anti-P. aeruginosa titer demonstrates that an exaggerated immune response to P. aeruginosa is associated with pulmonary damage in patients with cystic fibrosis. PMID- 1903200 TI - Regulatory factor-X binding to mutant HLA-DRA promoter sequences. AB - The class II genes of the major histocompatibility complex (MHC) encode a family of cell surface glycoproteins that present processed antigen to the T cell receptor. Class II genes are regulated coordinately, responding to both immunologic and developmental signals. Conserved sequence elements 5' to class II genes have been shown to be important in transcriptional control. One of these sequences, the X box, is a specific target for the binding of the factor RF-X. In the hereditary HLA class II deficiency, a form of primary immunodeficiency, a regulatory defect in expression of class II genes is associated with a defect in the binding of RF-X. To determine the basepairs that are important for this binding interaction, a series of single basepair substitutions spanning the X box motif of the DRA gene was constructed and tested for binding of RF-X by gel electrophoresis mobility shift assays (EMSAs). Several, but not all, of the mutants severely affected binding of RF-X. In addition, the binding of both the natural and the recombinant form of RF-X was affected with the same specificity. A comparison of X box basepair positions important for RF-X binding to DRA with sequences conserved between X boxes of other class II alpha chain genes suggests that high affinity RF-X binding is important for a high level of expression and may explain differences in the levels of class II expression of different class II alpha chains. PMID- 1903201 TI - Nearest neighbor effects on carcinogen binding to guanine runs in DNA. AB - A synthetic DNA fragment was constructed to determine the effect of 5' and 3' neighbors of guanine runs on the binding of chemical carcinogens. Determinations were made on the relative intensity of reactivity between aflatoxin B1 or benzo(a)pyrene and methylnitrosourea or 1-(2-chloroethyl)-3-cyclohexyl-1 nitrosourea with various guanine positions in an endlabeled DNA fragment of known sequence. After reaction, the fragments were depurinated to produce strand breaks to allow Maxam and Gilbert sequencing for guanine positions. Relative reaction intensities were compared densitometrically. 3' neighbors exerted greater influence on carcinogen binding than did 5' neighbors, the influence extended only to the adjacent guanine and depended upon the chemical nature of the carcinogen. In addition, the presence of one carcinogen adduct in the guanine run influenced the formation of a subsequent adduct when the DNA was exposed to a second carcinogen, and this effect also depended on the nature of the second carcinogen. The results suggest that DNA adduct formation in the presence of multiple carcinogens is more complicated than an additive mechanism would suggest. PMID- 1903202 TI - Homology between IRE-BP, a regulatory RNA-binding protein, aconitase, and isopropylmalate isomerase. AB - Iron-responsive elements (IREs) are regulatory RNA elements which serve as specific binding sites for the IRE-binding protein (IRE-BP). Interaction between IREs and IRE-BP induces repression of ferritin mRNA translation and transferrin receptor mRNA stabilization. We describe the identification of extensive amino acid sequence homology between IRE-BP and two known isomerases, aconitase and isopropylmalate (IPM) isomerase. We discuss the implications of this observation with regard to structure/function relationships of IRE-BP. The structural conservation between a regulatory RNA-binding protein and two enzymes involved in intermediary metabolism provides a surprising example of the functional flexibility in biological structures. PMID- 1903203 TI - A simple method for quantifying specific mRNAs in small numbers of early mouse embryos. AB - Amplification of sequences by the polymerase chain reaction (PCR) has become a powerful tool in the study of gene expression. The technique is, in fact, so powerful that it may detect 'leaky transcription'. Thus, it is now important to be able to quantify the transcripts that are amplified to determine whether or not they represent legitimate transcription of target genes. In this paper, we describe a one-step amplification reaction coupled to solution hybridization/RNase protection that is capable of quantitating specific transcripts in total RNA from one to ten preimplantation mouse embryos and is generally applicable to any cloned mRNA sequence. PMID- 1903207 TI - Stimulation of membrane phospholipid metabolism by agents that increase acidification in toad urinary bladder. AB - Previous reports have indicated that metabolic acidosis stimulates H+ excretion, and this excretion is accompanied by an increased turnover of phospholipids (PL) in toad urinary bladder. The purpose of this experiment was to determine if other known stimulators of H+ excretion [insulin, deoxycorticosterone acetate (DOCA), epinephrine, parathyroid hormone, and CO2] might also stimulate PL turnover in the toad urinary bladder. Quarter bladders from normal toads were removed, weighed, and then incubated with [32P]orthophosphate for 2 hr at 25 degrees C. PL were extracted, separated, and detected using thin layer chromatography and autoradiography, and quantitated by liquid scintillation counting. Results were expressed in cpm (100 mg bladder)-1 (hr)-1. One quarter bladder received insulin (100 milliunits/ml), DOCA (10(-6) M), epinephrine (50 mM), parathyroid hormone (100 micrograms/ml), or 5% CO2 during the incubation, whereas the paired quarter bladder received no treatment. Phosphatidylcholine (PC) and phosphatidylinositol turnover were increased by insulin (P less than 0.025 and less than 0.05, respectively). DOCA had no effect on PL turnover, but stimulated the percentage fraction of PC (P less than 0.05) expressed as percentage fraction of total lipids. Five percent CO2 in the bath resulted in an increased rate of turnover of the PL fractions phosphatidylinositol (P less than 0.05), and the phosphatidic acid plus phosphatidyl-serine (P less than 0.01). Epinephrine and parathyroid hormone were both without effect on PL metabolism. We conclude that insulin, DOCA, and CO2 may stimulated H+ excretion in toad bladder in part by increasing turnover of membrane PL, PC, and phosphatidylinositol, and in the case of CO2, phosphatidic acid plus phosphatidylserine as well, but not PC. PMID- 1903205 TI - Rapid isolation of long cDNA clones from existing libraries. PMID- 1903204 TI - Sequence preferences of DNA interstrand crosslinking agents: quantitation of interstrand crosslink locations in DNA duplex fragments containing multiple crosslinkable sites. AB - A general approach to the quantitative study of the sequence specificity of DNA interstrand crosslinking agents in synthetic duplex DNA fragments is described. In the first step, a DNA fragment previously treated with an interstrand crosslinking agent is subjected to denaturing PAGE. Not only does this distinguish crosslinked from native or monoadducted DNA, it is shown herein that isomeric crosslinked DNAs differing in position of the crosslink can in some cases be separated. In the second stage, the now fractionated crosslinked DNAs isolated from denaturing PAGE are subjected to fragmentation using iron(II)/EDTA. For those fractions which are structurally homogeneous, analysis of the resulting fragment distribution has previously been shown to reveal the crosslink position at nucleotide resolution. It is shown herein that in fractions which are structurally heterogeneous due to differences in position of crosslink, this analysis quantifies the relative extent of crosslinking at distinct sites. Using this method it is shown that reductively activated mitomycin C crosslinks the duplex sequences 5'-GCGC and 5'-TCGA with 3 +/- 1:1 relative efficiency. PMID- 1903206 TI - Alcohols protect Escherichia coli against cold shock. AB - Alcohols protect Escherichia coli against cold shock, and the concentration of alcohol which provided optimal protection declined with increasing hydrophobicity of the alcohol. The rate of loss of viability after the chilling transition was decreased by n-octanol, even when it was added after that chilling transition. Cold-shocked cells exhibited a sensitivity toward dioxygen, seen as greater enumeration on anaerobic, rather than on aerobic, trypticase-yeast extract agar plates, and addition of catalase or antioxidants, such as alpha-tocopherol or probucol, to the agar plates did not lessen this dioxygen sensitivity. Respiratory capacity was diminished by cold shock, and cyanide-sensitive respiration was more affected than was cyanide-resistant respiration. Discharging the proton gradient, with the uncoupler carbonyl cyanide trifluoromethoxy phenylhydrazone, did not change sensitivity to cold shock. There was no evidence for minimal medium recovery after cold shock. The data presented, as well as that already in the literature, are explained on the basis of membrane damage caused by patches of ordering transitions in one membrane leaflet, unmatched by comparable transitions in the mating leaflet. PMID- 1903209 TI - [Artificial feeding and respiratory insufficiency]. PMID- 1903208 TI - Early detection of damage following bilateral renal irradiation in the mouse. AB - The rate and early pattern of development of radiation-induced renal damage has been determined in the mouse by measuring reductions in both haematocrit and excretion of 51Cr-EDTA, and increases in both urination frequency and urine volume. Kidneys of CBA mice were irradiated bilaterally with 2 fractions of X rays, one week apart. Renal function was determined immediately prior to irradiation and at 3-4 weekly intervals to 22 weeks post-irradiation. Onset of damage was detected as early as 3-6 weeks using the urination frequency assay. This was confirmed by estimating the volume of urine excreted. A significant fall in haematocrit was not detected until 6-9 weeks post-treatment and a fall in isotope clearance was not detected significantly until 12 weeks. This early detection of damage was consistent with reports using both mouse and other species. The time at which damage was detected first was independent of radiation dose for the frequency and haematocrit assays. For 51Cr-EDTA clearance, there was the suggestion of earlier functional loss for the higher doses. Following the onset of damage, a steady, dose-dependent decline in renal function was measured by all assays. The latency period is defined as the time required to reach a given level of functional damage. This time decreased with increasing radiation dose, to a minimum value set by the time of onset of damage, which varied from 3 to 12 weeks, depending on the assay used. The differences in response measured prior to 12 weeks post-irradiation represent the first occasion on which a dissociation between these 3 assays has been detected.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1903210 TI - D-D recombination diversifies the CDR 3 region of chicken immunoglobulin heavy chains. AB - The occurrence of D-D recombination during the embryonic differentiation of chicken B cells was studied. Ig heavy (H) chains were amplified by polymerase chain reaction from day-12 bursal cDNA, and 30 random V-D-J regions were analysed by DNA sequencing. No gene conversion events were observed in any of the V regions, indicating that diversification of the H chains by gene conversion is not yet activated at this stage of embryonic B-cell development. In contrast, the V-D-J joint regions were extremely heterogeneous. Most of the sequenced V-D-J joints were formed by direct joining of the single-germline V mu 1 gene, one of the multiple-germline D elements, and the single J gene. However, three V-D-J regions were clearly longer in size, and their D-region structure indicated recombination between two or three different germline D elements. Thus, the present data suggest that D-D recombination may have a role in diversification of the Ig H-chain repertoire. PMID- 1903211 TI - Interferon-gamma enhances PAF-acether production by stimulated human polymorphonuclear leucocytes. AB - Human polymorphonuclear leucocytes (PMN) stimulated with either immune complexes (IC), phorbol myristate acetate (PMA) or N-formyl-methionyl-leucyl-phenylalanine (FMLP) generate platelet-activating factor (PAF-acether). The present study demonstrates that treatment of PMN with recombinant human interferon-gamma (IFN gamma) significantly enhanced the production of PAF-acether by stimulated cells, in a concentration-dependent mode. On the contrary, alpha and beta IFN were completely unable to increase PAF-acether synthesis by stimulated PMN. The significance of these results is discussed. PMID- 1903212 TI - Elastolytic activity of human monocytes from synovial fluid and blood of patients with arthritis. Relations to levels of interleukin 6 and soluble interleukin 2 receptor. AB - Synovial fluid (SF) and blood from 24 patients with non-traumatic, sterile hydarthron were examined for monocyte elastolysis (MoE) and for levels of interleukin 6 (IL-6) and of soluble interleukin 2 receptor (sIL-2R). Six patients had osteoarthrosis (OA) and 18 patients had inflammatory hydarthron (IH), 10 of whom had rheumatoid arthritis (RA). Blood MoE was lower in OA than in IH, both measured as basal MoE activity and after in vitro stimulation with immune complexes and phorbol myristate acetate (PMA). SF MoE was higher than MoE in blood (p less than 0.01). This increase in SF MoE could be mimicked in vitro by prestimulation of blood Mo with low levels of IC. SF IL-6 and sIL-2R were also elevated (p less than 0.01). All three parameters correlated to the degree of joint inflammation evaluated by SF leucocyte level, complement activation, blood C Reactive Protein, and to the clinical evaluation of the joint. The increase in SF MoE, IL-6 and sIL-2R in patients with IH, points to a stimulation of Mo and lymphocytes in the joint. PMID- 1903213 TI - [The classification of atypical forms of neurofibromatosis]. AB - Neurofibromatosis (NF) represents not an entity but a group of several forms which differ as to symptoms, prognosis and inheritance. In 1982 Riccardi suggested a classification into eight categories. Two of these--Von Recklinghausen NF-1 and bilateral acoustic NF-2- were defined in 1987 by a National Institutes of Health Consensus Development Conference. We describe 13 patients whose symptoms do not fit the diagnostic criteria for NF-1 and NF-2. 6 subjects can be classified as segmental NF-V. One of these patients was remarkable in having iris hamartomata, while his daughter was affected with NF-1. Another (female) patient in this group had areolar freckling, a finding not yet reported in NF patients. 4 cases belong to the late-onset NF-VII category, 3 of whom developed a neurofibrosarcoma. Two subjects are fist-degree relatives (mother and son). We are not aware of familial occurrence of NF-VII. Two further subjects were assigned to the variant form of NF, NF-IV. One patient had symptoms similar to NF-2 but the minimal diagnostic criteria were not fulfilled. Nevertheless, we consider his classification as NF-2 in view of a pattern of intracranial calcification repeatedly and exclusively found in NF-2. In general, assignment to a category of NF is important for appropriate patient management and genetic counselling. Classification of individual patients may be arbitrary at the time. PMID- 1903214 TI - Myoclonic epilepsy--pitfalls in diagnosis and management. AB - Three cases of myoclonic epilepsy presenting in adolescence are described. Seizures were uninfluenced by treatment with carbamazepine. Substitution of sodium valproate in early adult life resulted in all becoming seizure-free. A high degree of clinical awareness is required in making the correct diagnosis and in choosing appropriate therapy for this form of epilepsy which can present with generalised tonic-clonic or partial seizures. PMID- 1903215 TI - Erythropoietin--trials then tribulation. PMID- 1903217 TI - [The effects of intensive care for newborn infants]. AB - This article is based upon a research project on behalf of the Dutch ministry of Welfare, Health and Cultural Affairs. It will give the reader an overview of the main effects of intensive-care neonatology mainly on the basis of a literature research. In this article medical, psycho-social, economic, legal and ethical effects have successively been investigated. The major findings from existing published work in the neonatal field are discussed, highlighting some of the unresolved issues. Finally, some conclusions are drawn and some suggestions for further research are made. PMID- 1903218 TI - [Continuous arteriovenous hemofiltration and hemodiafiltration in a newborn infant with acute kidney insufficiency]. AB - A boy of 10 days old with acute renal failure was treated with continuous arterio venous hemofiltration and continuous arterio-venous hemodiafiltration over a period of 14 days. Hemodynamically both technics were well tolerated. Fluid overload was treated effectively by continuous fluid withdrawal and during continuous arterio-venous hemodiafiltration there was an adequate solute removal. One bleeding episode was observed during controlled general heparinization and was probably related to thrombopenia. In conclusion, continuous arterio-venous hemofiltration and hemodiafiltration are efficient modes of treatment in hemodynamically unstable infants in whom other forms of conventional dialytic therapy are contraindicated. Only continuous arterio-venous hemodiafiltration offers both fluid withdrawal and adequate solute removal and consequently may be preferred to continuous arterio-venous hemofiltration. PMID- 1903216 TI - Modulation of alkylating agents by lonidamine in vivo. AB - We are searching for relatively nontoxic compounds that can positively modulate the efficacy of antitumor alkylating agents. Lonidamine inhibits cellular energy metabolism and could potentially increase damage by alkylating agents if cellular defenses are energy-requiring. In the FSaIIC murine fibrosarcoma tumor system, 5 intraperitoneal (IP) injections of 50 mg/kg of lonidamine over 36 hours increased the tumor cell kill by cisplatin, carboplatin, D-tetraplatin, melphalan and BCNU approximately two- to threefold over the dosage ranges of each drug tested when the antitumor agents were given IP immediately after the third lonidamine injection. When cyclophosphamide and thiotepa were given in the same schedule, 10 fold increases in tumor cell killing were evident on tumor excision assay over the dosage ranges for each drug. The increase in bone marrow toxicity caused by lonidamine in addition to the alkylating agents, cisplatin, carboplatin, and BCNU was less than for tumor cells. Dose modifying effects were observed in the killing of bone marrow colony forming units-granulocyte-macrophage progenitors (CFU-GM) by cyclophosphamide, thiotepa and melphalan but at standard doses of cyclophosphamide and thiotepa there was no increase in the killing of bone marrow CFU-GM with the addition of lonidamine to treatment with these drugs. The results suggest that lonidamine can positively modulate tumor cell killing by some antitumor alkylating agents and may be a clinically useful adjunctive therapy with these drugs. PMID- 1903219 TI - [Breast feeding, PCBs and dioxins]. AB - In breastmilk of 14 Dutch mothers and 5 Polish mothers the content of dioxins and furans is measured. The study in Dutch mothers is started to relate the level of these xenobiotics to bleeding in the perinatal and late neonatal period. Interference with coagulation is hypothesized in analogon to phenobarbital. A relation is seen between bleeding in four babies and the mean content of 2, 3, 7, 8 TCDD (= tetrachloordibenzodioxin) (P = 0.02) in their breastmilk. This relation however is not found for the content of 2, 3, 4, 7, 8 PnCDF (= pentachloordibenzofuran) or the total amount of toxic equivalents. The fact that the prenatal gradient from mother to baby is different for T4CDD and PnCDF, respectively 2:1 and 10:1, may be an explanation for the dissociation between T4CDD on one side and PnCDF and total amount of toxic equivalents on the other side. Polish breastmilk was significantly lower (about four times) for dioxins and furans than Dutch breastmilk. This means that for these chemicals pollution in Holland is much higher than in Poland. PMID- 1903220 TI - Transient pure red cell aplasia caused by antilymphoblast globulin after cadaveric renal transplantation. AB - Transient pure red cell aplasia (PRCA) in three consecutive patients receiving ATG for management of kidney graft rejection prompted a systematic study of the effects on erythropoiesis of the ATG preparation used at our institution. We found that 90% of patients treated with rabbit anti-T lymphoblast globulin developed reticulocytopenia (less than 17,000 reticulocytes/mm3), with complete disappearance of reticulocytes in 65% of patients and increased requirement for red cell transfusion. PRCA, with selective aplasia of erythroblasts was confirmed by bone marrow aspiration in 4 patients volunteering for aspiration, and by the kinetic of the disappearance of blood reticulocytes in relation to the beginning of ATG treatment. The nadir of thrombocytes and lymphocytes, blood cells directly destroyed by ATG in circulation, followed the start of ATG treatment within 1 to 4 days. In contrast the nadir of reticulocyte counts occurred later, between day 7 and 13 after ATG was begun, reflecting the fact that toxicity was directed against red cell precursors rather than mature circulating cells. In agreement with these clinical findings ALG was found to be cytotoxic in vitro for erythroid precursors. Analogously to autoimmune PRCA caused by autoantibodies to erythroblasts, this type of PRCA could be viewed as "heteroimmune disease." PMID- 1903221 TI - Evidence that cyclosporine treatment during pregnancy predisposes offspring to develop autoantibodies. AB - Cyclosporine was administered (11 mg/kg/day) to pregnant mice to study the effects of passively transferred CsA on the developing immune system. Placental transfer of CsA was shown by the detection of fetal-tissue levels ranging from 400 to 1500 ng CsA/g tissue. Treatment clearly altered the developing immune system. Thymuses from the day-18 embryos exposed to CsA were partially depleted of CD4+CD8- single positive cells. Eleven of 50 offspring born to CsA-treated mothers developed significant levels of IgG autoantibodies to gastric antigens. In addition, two animals that received CsA in utero developed an extensive mononuclear cell infiltrate in the gastric mucosa resembling autoimmune gastritis. These results raise the possibility that the administration of CsA during pregnancy may result in potential long-term effects on the developing immune system. Offspring of such pregnancies may suffer an increased incidence or severity of autoimmune diseases. PMID- 1903222 TI - Rapid increase in the activity of enzymes of eicosanoid synthesis in hepatic and extrahepatic tissues after experimental liver transplantation. AB - Previous studies have demonstrated a marked release of prostanoids from hepatic tissue after liver grafting. In addition, eicosanoid synthesis was shown to be regulated at the level of key enzymes. The present study addressed changes of the local availability of these enzymes during and after porcine orthotopic liver transplantation. We determined kinetic parameters of cyclooxygenase (CO), the initial enzyme of prostaglandin synthesis, of prostacyclin and thromboxane synthase (PCS, TXS), two more peripheral enzymes, in microsomal preparations of hepatic and gluteal muscle biopsies, and the activity of 5-lipoxygenase (5-LO), the key enzyme of leukotriene synthesis. Maximal velocity (Vmax) of CO and PCS showed a 4-fold increase both in liver and gluteal muscle tissue 1 hr after reperfusion of the grafted liver and a more than 20-fold increase after 24 hr (P less than 0.001), whereas apparent affinities (Km) remained unchanged. In contrast, Vmax of TXS and the activity of 5-LO disclosed a striking increase only within the hepatic graft (P less than 0.001). No changes of enzymatic activity could be observed during donor operation, cold storage, and 5 min after reperfusion. Results were independent of the duration of preservation (3 hr and 20 hr with Euro-Collins) and the addition of Iloprost, a prostacyclin-analogue. These results suggest that after liver grafting, abnormalities at the level of local enzyme expression in hepatic and extrahepatic tissues might contribute to preservation damage and systemic injury of the host. PMID- 1903223 TI - The effect of the graft-versus-host reaction on B lymphocyte production in bone marrow of mice. Depressed genesis of early progenitors prior to mu heavy chain expression. AB - The effects of systemic graft-versus-host (GVH) reactions on the early precursor cell populations involved in primary B lymphocyte genesis have been examined in the bone marrow of (C57BL/6xA)F1 mice injected with lymphoid cells from A strain mice. Double immunofluorescence labeling techniques for the intranuclear enzyme, terminal deoxynucleotidyl transferase (TdT), the B220 cell surface glycoprotein detected by monoclonal antibody, 14.8, and surface or cytoplasmic mu chains of IgM (s mu, c mu) were used to quantitate 3 putative early B lineage progenitors preceding mu chain expression (TdT+14.8-mu-, TdT+14.8+mu- and TdT-14.8+mu-), pre B cells (c mu+, s mu-) and B lymphocytes (s mu+). After initiating GVH reactions, the early B precursor cells, pre-B cells, and B lymphocytes in the bone marrow all fell rapidly in numbers, being almost completely absent from 10-15 days to the end of the 30-day assay period. The decline of some of the early progenitors started at a later time and was less complete than that of the more differentiated B lineage cells. In the spleen, B lymphocytes declined rapidly in numbers after 8 days to less than 5% of normal values from 12 days onward. The results demonstrate that systemic GVH reactions in mice almost completely eliminate the B cell lineage, including early precursor cells apparently undergoing mu chain rearrangement in the bone marrow. The pattern of depletion suggests that a range of B lineage progenitor cells may be directly susceptible to GVH reactions. The findings contribute to a model for the pathogenesis of the humoral immunodeficiency of systemic GVH disease. PMID- 1903224 TI - Tissular prostanoid release, phospholipase A2 activity, and lipid peroxidation in pancreas transplantation. AB - Free radical species have been implicated as important agents in ischemia reperfusion injury associated to transplantation procedures. This study was carried out to investigate the possible relationship between phospholipase A2 activity (PLA2), lipoperoxidation, and the changes in arachidonic acid metabolism during ischemia reperfusion injury in pancreas transplantation, as well as the effect of a free radical scavenger such as superoxide dismutase on these changes. For this purpose male Lewis rat groups (n = 7) were classified as follows: group I--control; group II--syngenic pancreas transplantation after 15 min preservation in Collins solution at 4 degrees C; group III--syngenic pancreas transplantation after 18 hr preservation in the same conditions; group IV--same as III but with administration of SOD (i.v.) immediately before revascularization in the recipient rat. The results indicate that significant increases in PLA2 activity and lipoperoxide levels occur concomitantly with an increase of thromboxane B2 (TXB2) and 6-keto prostaglandin F1 alpha (6-keto PGF1 alpha) in pancreatic tissue after pancreas transplantation. The counteracting effect of a free radical scavenger such as SOD supports the role of oxygen free radicals (OFR) mediating activation of PLA2 and subsequent formation of eicosanoids in pancreas transplantation. PMID- 1903225 TI - Superoxide dismutases of virulent and avirulent strains of Brucella abortus. AB - Extracts of Brucella abortus strains 2308,RB51,45/20 and ST 19 had no significant differences in superoxide dismutase (SOD) activity as measured by the epinephrine assay. These B. abortus strains represent smooth, intermediate and rough colony forms. SOD activity was inhibited 60 to 75% by 2 mM KCN and suggests the presence of Cu/Zn SOD. The SOD activities were similar when the strains were grown in trypticase soy broth containing either 0.5% glucose or erythritol. There were two distinct SOD activity bands in native polyacrylamide gel electrophoresis with identical mobilities for each of the strains. When the native gel was stained for SOD activities in the presence of 2 mM KCN, the SOD band that co-migrated with the bovine erythrocyte Cu/Zn SOD activity disappeared. The band of SOD activity that migrated similar to E. coli iron SOD activity was unaffected by KCN. There were no significant differences in either the total SOD or Cu/Zn SOD activities among the strains. As the Brucella strains represent ranges of virulence, it is difficult to associate any primary role for SOD as a virulence factor. PMID- 1903226 TI - [Activation of the Ha-ras oncogene in tumors induced in mice by transplacental exposure to 7,12-dimethylbenz(a)anthracene]. AB - A study of tumors induced in mice by transplacental exposure to 7,12 dimethylbenz(a)anthracene (DMBA) alone or in combination with postnatal tissue specific promotion showed skin and liver tumor development to be associated with cellular Ha-ras oncogene activation in a large percentage of cases. As shown by Xba I RFLP, oncogene activation was caused by T for A substitution at the second position of codon 61. The said mutation was traced in DMBA-induced tumors of the liver alone but not in spontaneous hepatomas. The results of the study showed the role of oncogene activation in cancer development to be tissue-specific. PMID- 1903227 TI - Comparison of monocyte-monolayer assay with anti-D and some non-anti-D antibodies. PMID- 1903228 TI - The yellow brick road. PMID- 1903229 TI - [Karl Landsteiner (1868-1943) in memoriam]. AB - Apart from the discovery of the human blood groups and the Rhesus factor Landsteiner developed the visualization of Spirochaeta pallida by the method of dark field microscopy. Furthermore, he demonstrated the transmission of poliomyelitis to monkeys, which made it possible to prove the viral origin of this disease. He gave fundamental impulses to the development of immunobiology (e.g. concept of haptens, specificity of antigens etc.). PMID- 1903232 TI - Surgical complications of Chagas' disease: megaesophagus, achalasia of the pylorus, and cholelithiasis. AB - Three surgical complications of Chagas' disease--megaesophagus, achalasia of the pylorus, and cholelithiasis--were evaluated within the framework of the experience acquired in the management of 840 cases of megaesophagus--722 in the nonadvanced stage of the disease and 118 with advanced disease (dolichomegaesophagus). In the group of the 722 patients with nonadvanced disease, achalasia of the pylorus was present in 140 (19.4%), and in the total of 840 patients, uncomplicated cholelithiasis without chagasic involvement of the gallbladder and/or papilla was observed in 58 (6.9%). The 722 subjects with nonadvanced megaesophagus were submitted to wide esophagocardiomyectomy performed at the level of the anterior esophagogastric junction, combined with an antireflux valvuloplasty procedure. We recorded no mortality, and 95% excellent and good results in long-term follow-up. On the other hand, dolichomegaesophagus required esophageal resection with reconstruction by means of an esophagogastroplasty placed in the esophageal bed. The mortality rate was 4.2% (5/118); the main postoperative complications were pleural effusion (22%) and fistulas of the esophagogastric anastomosis (8.4%). Postoperatively, the patients adapted well to their new anatomy and gained weight. Achalasia of the pylorus was confirmed by delayed gastric emptying time. This entity was managed by concomitant antropyloromyectomy without mortality. Cholelithiasis was managed by cholecystectomy and radiologic exploration of the bile ducts. PMID- 1903231 TI - Surgery of chagasic megacolon. AB - Chagas' disease is an endemic clinical entity caused by Trypanosoma cruzi, a parasite that is transmitted to humans by the hematophagic Triatominae insects. It affects several million persons in Latin America, mostly in Brazil, Argentina, Chile, Paraguay, and Bolivia. Megacolon, the most common complication of intestinal trypanosomiasis, results in severe constipation, for which surgery is indicated. A variety of procedures have been proposed for the correction of this disabling condition including sigmoidectomy, abdominal rectosigmoidectomy, left colectomy, and subtotal colectomy. On long-term follow-up, however, these operations have proved to be inadequate in a significant number of cases, apparently due to preservation of the dyskinetic rectum which continues to act as a functional obstacle to the progression of the fecal bolus. On the other hand, pull-through operations, which include the removal of all or almost all of the dyskinetic rectum, or the exclusion of the rectum, as in the Duhamel-Haddad operation, have been demonstrated to be superior. The abdominoperineal endoanal pull-through resection with delayed colorectal anastomosis and the Duhamel-Haddad operation are the most accepted procedures in Brazil and other Latin American countries; their technical details are illustrated. Functional results are satisfactory. Anal continence is normal in the vast majority of cases and sexual disturbances are rare. Routine treatment of 2 main complications--fecaloma and volvulus of the sigmoid colon--are discussed. PMID- 1903233 TI - [Effect of mutagenesis at Ser 177 residue in penicillin G acylase on activity of the enzyme]. AB - The technique of cassette and site-specific mutagenesis were used to study the role of residue No. 177 in penicillin G acylase (PGA, EC 3.5.1.11). Ser is conserved at residue No. 177 in all penicillin binding proteins. We got a series of mutants in which the amino acid at residue No. 177 was replaced by other amino acids through the site-specific and cassette mutagenesis, and we characterized the mutants by colony hybridization, NIPAB paper test and DNA sequence analysis. These mutants all show no activity of enzyme, even if the Ser residue was replaced by Thr, Gly and Ala respectively. The results show that Ser residue may be essential for substrate-binding or catalysis of PGA. PMID- 1903230 TI - Portal hypertension in mansonic schistosomiasis. AB - Mansonic schistosomiasis is an endemic disease in Brazil, with an estimated 10-12 million people infested. Among its clinical manifestations, the hepatosplenic form causes portal hypertension which, in turn, brings about severe digestive hemorrhage, the most serious complication of the disease. Normally, the patients are young, and have hepatosplenomegaly, hypersplenism without clinical manifestations, and slightly reduced hepatic function. The angiographic findings are characteristic, differing from those of hepatic cirrhosis. In Brazil, the definitive treatment for gastrointestinal hemorrhage is surgery, which should be done under elective conditions whenever possible. During a short period of time, known as the "risk period" (the time between the hemorrhagic episode and the surgery), propranolol has been used to prevent further bleeding. Surgical treatment is indicated only after the first episode, and never on a prophylactic basis. In 1977, a prospective, randomized trial was begun in order to assess the delayed results of the 3 surgical operations most widely used in this country. The study was interrupted after 94 patients had been operated on due to the high incidence of encephalopathy in the group who underwent classical splenorenal shunt. After a follow-up of at least 60 months and, at most, 130 months, the results showed that classical splenorenal shunt caused encephalopathy in 39.3% of the cases and distal splenorenal shunt in 14.8%. None of those submitted to esophagogastric devascularization with splenectomy developed encephalopathy. The 3 procedures showed similar rates of hemorrhagic recurrence. PMID- 1903234 TI - Urinary luteinizing hormone testing and prediction of ovulation in spontaneous, clomiphene citrate and human menopausal gonadotropin-stimulated cycles. A clinical evaluation. AB - A urinary luteinizing hormone test was utilized to predict ovulation in 99 spontaneous, 122 clomiphene citrate, and 82 human menopausal gonadotropin stimulated cycles. Tests were performed in early morning and evening specimens and follicular development was monitored by daily ultrasonography. A positive detection rate of 98, 97, and 94%, respectively, was obtained. Evidence of luteinized unruptured follicles was seen more frequently in stimulated cycles, concurring with negative test results. In 2 spontaneous, 1 clomiphene citrate and 5 hMG induced cycles two distinct LH surges were detected concomitant with a pattern of follicular atresia and subsequent new follicular development. Most ovulations occurred between 16 and 28 h after LH detection, significantly earlier in spontaneous than in clomiphene citrate stimulated cycles (p less than 0.02), whereas pre-ovulatory follicles were larger in the clomiphene citrate group (p less than 0.001). The mean duration of the follicular and luteal phases, as calculated from the LH peak, was substantially shorter in the hMG cycles than in the other two groups (p less than 0.001). PMID- 1903235 TI - Subtle primary hypothyroidism in patients treated for acute lymphoblastic leukemia. AB - We evaluated serum thyroid hormone and thyroid antibody levels, the serum TSH response to TRH, and the circadian pattern of serum TSH in 10 children and adolescents after radiation therapy for acute lymphoblastic leukemia. Four patients had received central nervous system preventive cranial irradiation and intrathecal chemotherapy, and the remaining 6 patients were treated with craniospinal irradiation for central nervous system relapse. Serum total T4 and T3 concentrations were within the normal range and thyroid antibodies were negative in all patients. Four patients who had received craniospinal irradiation had low free T4 levels. Prior to TRH administration, the overall mean serum TSH concentration was 5.4 +/- 1.3 mU/l, and the mean peak response to TRH was 33 +/- 6.5 mU/l. Both were significantly increased when compared to the levels observed in our control population (p less than 0.05 and less than 0.025, respectively). The overall mean nadir diurnal TSH was 3.6 +/- 0.8 mU/l, and the mean peak nocturnal TSH was 6.9 +/- 1.3 mU/l, both significantly elevated when compared to normal children (p less than 0.025). The mean nocturnal TSH surge, however, was not significantly different from normal. Four of 6 children treated with craniospinal irradiation, and one of four children treated with cranial irradiation had increased basal and peak serum TSH concentrations in response to TRH. One of the patients treated with cranial irradiation had an abnormal nocturnal TSH surge. We conclude that subtle primary hypothyroidism is relatively common in patients with acute lymphoblastic leukemia, particularly in those who have been treated with craniospinal irradiation. PMID- 1903236 TI - Hypothalamo-pituitary function and dopamine dependence in untreated parkinsonian patients. AB - Altered prolactin and thyrotropin responses to the TRH test in parkinsonian patients are held to indicate an impairment of the tubero-infundibular dopaminergic axis (TIDA). We correlated the plasmatic prolactin (PRL), thyrotropin (TSH) and somatotropin (GH) responses to TRH and bromocriptine + TRH of 12 parkinsonian patients, who had never received anti-parkinsonian drugs, with the severity, the duration, the age of onset and the dopamine-dependence of the motor symptomatology as indicated by the therapeutic response to a six-month oral treatment with bromocriptine. Patients with basal motor impairment over 9 on the Webster Rating Scale (WRS), those with duration of the disease over 24 months and those with onset earlier than 55 years of age showed lower PRL responses than the respectively matched subgroups. Patients showing a therapeutic motor improvement over 50% on the WRS (dopamine-dependent or "responder") showed lower PRL and TSH and higher GH responses than the non-responders. These findings suggest that the TIDA impairment described in Parkinson's disease develops along with the progressive course of the extrapyramidal involvement and is strictly correlated with the dopamine-dependence of the motor impairment. PMID- 1903237 TI - Refractory depression: the addition of lithium to fluoxetine or desipramine. AB - We carried out an open clinical study with 60 consecutive patients suffering from major depression with melancholia who were resistant to anti-depressants. After at least 6 weeks of desipramine (DMI) or fluoxetine (FX) without improvement, lithium carbonate was added to the anti-depressant. Semistructured clinical interviews using the 7-point Clinical Global Impression Scale and 90-item Symptom Checklist were done at baseline and weeks 1, 6 and 14. Following the addition of lithium, more patients on FX improved within the first week than those on DMI. However, with FX, 6 relapses occurred during the 2 months of follow-up and none with DMI. The unified serotonergic and noradrenergic hypothesis for the antidepressant action could be relevant in drug-refractory depression and should be studied further. PMID- 1903238 TI - Thyroid abnormalities during lithium treatment. AB - Thyroid function was evaluated in 150 Sardinian outpatients at different stages of lithium treatment. A visible and/or palpable goitre was found in 51% of patients, and there was no apparent correlation with the duration of treatment. No cases of symptomatic hypothyroidism were observed, but subclinical hypothyroidism was present in 19% of patients. The prevalence of specific antithyroid antibodies was positively correlated with age and duration of lithium treatment, and was higher in women. Subclinical hypothyroidism was observed in 53% of antibody-positive lithium-treated patients. Carbamazepine in combination with lithium was associated with significantly lower levels of total T4 and T3 than with lithium alone, and the ratios between total and free hormones were also decreased. PMID- 1903239 TI - Congenital nasal masses: CT and MR imaging features in 16 cases. AB - The imaging studies of 16 children with pathologically proved nasal encephaloceles (eight), nasal dermal sinuses/nasal dermoids (seven), and nasal cerebral heterotopias, more commonly known as nasal gliomas (one), were retrospectively reviewed and compared with normal control subjects to define the normal anatomy and analyze deformities caused by these lesions. Nasal encephaloceles were always identified as complex masses of mixed soft tissue and CSF intensity that were contiguous with intracranial structures. The nasal glioma appeared as a mixed-intensity mass that, on the basis of the CT scan, appeared to be continuous with intracranial structures. Nasal dermal sinuses could only be identified as they coursed through the skin and subcutaneous soft tissue. They could not be identified when intraosseous. Moreover, on CT and, particularly, on MR, a number of potential diagnostic pitfalls were encountered. The most important of these was the normal fat deposition that occurs within bone during normal maturation and during aeration of the frontal sinuses and nasal bones. These fatty changes can easily be mistaken for fatty tumors if they are not recognized as normal anatomic changes. Interestingly, the classic plain film findings for congenital nasal masses were present only in the encephaloceles and nasal glioma; dermoids and dermal sinuses showed none of the classic plain film findings. In the six patients who had both CT and MR, the masses were easily identified and characterized by each imaging method. Congenital nasal masses are well characterized by both CT and MR. It is important to understand the normal changes in the anatomy of the nasofrontal region in the pediatric age group to avoid false-positive diagnoses in this region. PMID- 1903241 TI - Increased incidence of nosocomial pneumonia in mechanically ventilated patients with subclinical aspiration. AB - Nosocomial pneumonia is frequent and is associated with high mortality in intubated mechanically ventilated patients. To determine whether there is a significant relationship between subclinical aspiration from nasogastric feeding and development of nosocomial pneumonia, we studied 24 ventilated patients who received nasogastric feeding. Endotracheal aspirates were tested twice daily for the presence of glucose using a glucose oxidase reagent strip. Subclinical aspiration was defined by the presence of glucose in nonbloody endotracheal aspirates. Nosocomial pneumonia was defined by the presence of all of the following conditions: (1) new or worsening infiltrate on chest roentgenogram consistent with pneumonia, (2) temperature greater than 38 degrees C and/or white blood cell count greater than 10,000/mm3 with 10% or more band forms, (3) culture of a new organism in the sputum, and (4) purulent tracheobronchial secretions. Twelve patients had no positive glucose tests of their endotracheal aspirates during their intensive care unit stay, one of whom developed nosocomial pneumonia. Twelve patients had endotracheal aspirates that were positive for glucose on 1 to 5 occasions. Of these patients, seven had bloody glucose-positive aspirates, four of whom developed clinical pneumonia. The remaining five patients had nonbloody glucose-positive endotracheal aspirates and all developed nosocomial pneumonia. There was a significantly greater incidence of pneumonia among patients who had nonbloody glucose-positive aspirates than among patients without glucose-positive aspirates (p less than 0.001, Fisher's exact test). We conclude that subclinical aspiration of nasogastric feeding, as detected by nonbloody glucose-positive endotracheal aspiration, is associated with the development of nosocomial pneumonia. PMID- 1903240 TI - MR evaluation of spinal dermal sinus tracts in children. AB - The MR studies of seven pediatric patients with surgically proved spinal dorsal dermal sinuses were reviewed retrospectively. Five of the seven had associated congenital tumors (three epidermoids, two dermoids). The subcutaneous portions of the spinal tracts and intramedullary portions of tumor were easily identified with the use of standard spin-echo techniques. However, except for limited areas where they were lined by fat, the intraspinal portions of the dermal sinuses were poorly seen. Moreover, diffuse subarachnoid tumor was missed in two patients. Three-dimensional Fourier transform gradient-echo acquisition using a volumetric radiofrequency pulse as a "spoiler" proved to be helpful in evaluating these abnormalities. Optimal radiologic workup of patients with dorsal dermal sinuses awaits the development of new MR imaging sequences. For now, heavily T1-weighted MR sequences should be obtained and supplemented with sonography in infants and with CT myelography in older children. PMID- 1903242 TI - Genetic and molecular bases of neurogenesis in Drosophila melanogaster. PMID- 1903243 TI - Stimulus-transcription coupling in the nervous system: involvement of the inducible proto-oncogenes fos and jun. PMID- 1903245 TI - Low birthweight infants: immediate feeding recalled. PMID- 1903244 TI - Gonadal function after allogenic bone marrow transplantation for thalassaemia. AB - Thirty prepubertal patients with thalassaemia major (15 boys and 15 girls) aged from 9.3 to 17.2 years (mean 12.9) who had successfully undergone allogenic bone marrow transplantation were studied. Before the transplant all patients were given short courses of high doses of busulphan (total dose 14 mg/kg) followed by cyclophosphamide (total dose 200 mg/kg). Pituitary gonadal function was assessed between 0.7 and 5.1 years (mean 2.3) after bone marrow transplantation. Increased gonadotrophin concentrations indicating gonadal damage were found in 80% of the girls, probably as a result of the chemotherapy. In all the prepubertal boys the basal follicle stimulating hormone and luteinising hormone concentrations were normal. Most of the boys had reduced gonadotrophin and testosterone responses after gonadotrophin releasing hormone and human chorionic gonadotrophin tests. This could have been the result of iron overload but the effect of cytotoxic agents cannot be excluded. These findings emphasise the need for vigilant long term follow up of thalassaemic patients treated with cytotoxic chemotherapy for bone marrow transplantation so that those requiring hormone replacement can be identified and treated. PMID- 1903246 TI - A clinical trial of two parenteral nutrition solutions in neonates. PMID- 1903248 TI - [Fusion for better quality?]. PMID- 1903247 TI - Detection of anti-Ro(SSA) antibodies by gel double diffusion and a 'sandwich' ELISA in systemic and subacute cutaneous lupus erythematosus and Sjogren's syndrome. AB - A newly described Ro 'sandwich' ELISA was compared to the gel double diffusion technique to detect anti-Ro(SSA) antibodies in Sjogren's syndrome, systemic and subacute cutaneous lupus erythematosus patients. This study demonstrates that the ELISA assay increased the frequency of detection of anti-Ro(SSA) antibodies in these well defined connective tissue disease patients by approximately 5-10% compared to the gel double diffusion anti-Ro(SSA) antibody assay. The study also confirms that some patients make anti-Ro(SSA) antibodies directed solely at unique human Ro(SSA) antigen epitopes. We also detected the existence of a significant Sjogren's syndrome patient population failing to make significant anti-Ro(SSA) antibodies. We conclude from our study that the gel double-diffusion technique employing human spleen extract as a source of the Ro(SSA) antigen is, at present, the most cost-effective test to detect anti-Ro(SSA) antibodies. PMID- 1903250 TI - [Gemini Hospital in Den Helder. After the test of courage a view of the sea]. PMID- 1903251 TI - [Worries about nursing care. Worries about the hospital]. PMID- 1903249 TI - [Questions with rehabilitation? A reaction to 'Experiences with Rehabilitation' by Verdult and Visser--TvZ No. 15, 1990]. PMID- 1903252 TI - [Worries about nursing care. Worries about community health services and nursing]. PMID- 1903253 TI - [Fatigue in elderly patients: a nursing problem? Nursing interventions (2)]. PMID- 1903254 TI - [Nursing diagnosis: common knowledge? Report of a study]. PMID- 1903256 TI - [The community health nurse and the central caregiver (1). Methodological approach]. PMID- 1903255 TI - [Care and social awareness]. PMID- 1903257 TI - [The inspection. Thinking along as an active outsider]. PMID- 1903258 TI - [Working with nursing care plans in the care for mentally retarded. An inventory taking in intramural institutions]. PMID- 1903259 TI - [Nurses may remain silent. The right to refuse to answer questions and nurses]. PMID- 1903260 TI - HIV-1 indicator cell lines. AB - A simple quantitative bioassay for infectious HIV-1 has been developed. The assay is based on adherent CD4+ HeLa cell lines stably transfected with episomal vectors carrying the Escherichia coli beta-galactosidase gene under the control of the HIV long terminal repeat (LTR) promoter. HIV infection of these cell lines transactivates the LTR promoter inducing beta-galactosidase production. Infected cells and virus foci can be stained dark blue by the addition of the chromogenic substrate X-Gal. Alternatively, a readily automatable quantitative enzyme assay can be performed on the infected cultures. Because of its simplicity the bioassay may be useful for routine quantification of HIV-infected cultures, plaque purification, virus neutralization studies and for the screening of antiviral agents. PMID- 1903261 TI - Racial heterogeneity of HIV antigenemia in people with HIV infection. AB - We compared the prevalence of HIV p24 antigenemia in black and white US patients with HIV infection. The prevalence of HIV antigenemia increased with severity of HIV disease (P less than 0.001). In all clinical categories, whites were more likely to be HIV-antigenemic than blacks (overall prevalence 38 versus 18%; P less than 0.01). Anti-p24 antibodies were detected in a higher proportion of blacks (84%) than whites (65%; P = 0.02). Blacks had significantly higher total serum immunoglobulin levels than whites (median 3.8 versus 3.2 mg/dl; P less than 0.00001). Racial differences in HIV antigen expression may result from differences in humoral response to HIV infection. These differences should be considered when HIV antigen is used as a surrogate marker in clinical trials. PMID- 1903262 TI - CD8+ T lymphocytes and progression to AIDS in HIV-infected men: some observations. AB - The relationship between CD8+ lymphocyte counts and progression to AIDS was studied in 340 HIV-1-seropositive men participating in a population-based prospective study. Overall, the relative hazard for developing AIDS during 60 months of observation was slightly elevated (1.08, P = 0.003), indicating an 8% increase in risk of progression for every 100 CD8+ cell count increment. When the data were analyzed in relation to date of diagnosis, the relative hazard was depressed (0.90, P less than 0.001) for the period 6 months prior to diagnosis, but was close to 1.0 for the period 6-36 months prior to diagnosis. These findings suggest a complex relationship between CD8+ cell counts and progression to AIDS, with the possibility that various subsets of the CD8+ compartment play different roles. PMID- 1903263 TI - The puh structural gene coding for the H subunit of the Rhodospirillum rubrum photoreaction center. AB - The Rhodospirillum rubrum structural gene puh, coding for the photoreaction center H polypeptide, and three other putative genes that surround puh were cloned and sequenced. The deduced 257 amino acid H polypeptide has a molecular weight of 27,909, in close agreement with polyacrylamide gel electrophoresis determination. Hydropathy plots predict a single hydrophobic alpha helix. The H polypeptide of Rhodospirillum rubrum shares only 23% of its residues with all three of the H polypeptides from Rhodopseudomonas viridis, Rhodobacter capsulatus, and Rhodobacter sphaeroides. Despite this apparent low degree of similarity, statistical analysis leaves no doubt about their close relatedness. Interspecies evolutionary distance, assessed by this analysis, confirms the closeness of the two Rhodobacter species, Rhodospirillum rubrum and Rhodopseudomonas viridis being approximately equidistant from them. Three regions of the H polypeptide are highly conserved in all four species. They correspond to known contact points of H with the complex of the other two (L and M) subunits on the cytoplasmic side of the membrane. A glutamic acid residue (H polypeptide residue 177), conserved in the other bacteria and suggested to be involved in the binding of secondary quinone QB, is replaced by serine in Rhodospirillum rubrum. The open reading frames G115, I2372, and I3087 are predicted to, respectively, encode polypeptides of 480, 224, and 155 residues coiled in 10, 2, and 1 transmembrane helices. Open reading frame G115 shares 56% identical residues with F1696, a sequence arranged in the genome of Rhodobacter capsulatus. The gene product of ORF I3087 is predicted to share highly similar sequences with nitrogenase reductase (encoded by nifH) of 11 different bacterial species and is suggested to have a regulatory function. PMID- 1903264 TI - Management of myocardial infarction in the community: a new RCGP study. PMID- 1903265 TI - Percutaneous duodenostomy--alternative route for enteral nutrition. AB - Percutaneous translumbar duodenostomy for enteral feeding was performed in one patient with nutritional difficulties. No complication was encountered. The procedure can be an alternative to percutaneous gastrostomy and jejunostomy for enteral feeding in special situations. PMID- 1903266 TI - The Hering-Breuer reflex in man? PMID- 1903267 TI - Recurrent haemolytic uraemic syndrome in a transplant recipient on orthoclone (OKT 3). AB - Recurrence of haemolytic-uraemic syndrome (HUS) after renal transplantation may occur in both cyclosporin A (CyA) and non-CyA-treated patients, and in patients receiving anti-lymphocyte globulin. We report a case of recurrent HUS in an 8 year-old boy who received Orthoclone (OKT3) combined with prednisolone and azathioprine therapy on receipt of his first cadaveric renal allograft. Despite avoidance of CyA therapy irreversible HUS occurred. PMID- 1903269 TI - Scottish excellence. Management for the nineties. PMID- 1903270 TI - Scottish excellence. Developing excellence. PMID- 1903268 TI - Distal renal tubular acidosis: the value of urinary pH, PCO2 and NH4+ measurements. AB - Distal renal tubular acidosis (dRTA) is not a single disease. The experimental forms of the syndrome are unsatisfactory as models of the naturally occurring disease, not least because they are seldom complicated by nephrocalcinosis, which is present in the majority of patients with spontaneous disease and contributes to the renal tubular defects found in the syndrome. Impairment of minimal urine pH, reduced urine carbon dioxide tension (PCO2) during passage of alkaline urine, and reduced urinary ammonium (NH4+) excretion, have all been advocated as essential criteria for the diagnosis of dRTA. Minimal urine pH, measured during metabolic acidosis, sulphate infusion, or after oral frusemide, is the yardstick against which other criteria should be assessed. A reduced urinary PCO2 is commonly found in dRTA but is not specific for the syndrome and may be accounted for by tubular defects other than those involving reduced distal hydrogen ion secretion. NH4+ excretion is reduced in most patients with renal acidosis whatever the nature of the underlying renal disease; this function is closely related to nephron mass, and is not specifically impaired in renal tubular disease. PMID- 1903271 TI - Elderly people: attitudes towards urinary incontinence. PMID- 1903272 TI - Clinical supervision: psychiatric students. PMID- 1903274 TI - Influenza: causes and incidence. PMID- 1903273 TI - Ward management: reflection and the charge nurse. PMID- 1903275 TI - Introducing resource management. PMID- 1903277 TI - Critical care. Honorary officers in critical care. PMID- 1903276 TI - Critical care. A critical platform. PMID- 1903278 TI - Critical care. A unique specialty. PMID- 1903279 TI - Critical care. Open to discussion. PMID- 1903280 TI - Critical care. Setting standards in intensive care. PMID- 1903281 TI - Reasons why people refuse HIV tests. PMID- 1903282 TI - Union merger. Towards a superunion. PMID- 1903283 TI - Negligence: the new accountability. PMID- 1903284 TI - Child health. Cause for concern. PMID- 1903285 TI - Narrative of excellence. PMID- 1903286 TI - Student nurses and children's pain. AB - The issue of pain assessment has attracted great interest in recent years, but there are as yet precious few studies which concentrate on paediatric nurses' assessment skills. Sue Price describes a study of how first-level (general) student nurses assessed children's pain. Despite a small sample size, she found wide variation in understanding of the intensity of pain being suffered by children. She recommends the inclusion of a session on the assessment and management of pain in the paediatric module of general nursing syllabuses. PMID- 1903287 TI - Wrong to be an angel? PMID- 1903288 TI - Strabismus: diagnosis and management. AB - The problem of squint can pose problems which extend far beyond the limits of cosmetic considerations. To coincide with National Squint Awareness Week, co ordinator Pat Goodwin describes the aetiology, treatment and management of the various conditions associated with squints. PMID- 1903289 TI - Nurse education in the market place. AB - The education and training of health service professionals and non-professionals is set to be driven by a market-place philosophy which will exert and endorse competition and control via rapidly evolving change and reform. Helen Field's article seeks to provide an outline of such reform within the National Health Service education and training arena. In particular, it considers how the education of nurse professionals will fare in a system which focuses more accurately on efficiency, cost effectiveness, quality and marketing of educational provision. PMID- 1903290 TI - Educational support in palliative care. AB - Approval by the National Board of Scotland as a clinical area for students on the Professional Studies II module on care of the terminally ill acted as a stimulus for staff at a nursing home to seek help in developing psycho-social, self awareness and support skills. Margaret Campbell Sneddon and Patricia Eagle initiated a course which aimed to meet the needs and expectations of the staff. PMID- 1903291 TI - Points of view. PMID- 1903292 TI - Preaching for the converted. PMID- 1903293 TI - Sales-nurse wanted. PMID- 1903294 TI - Hobson's advocate. PMID- 1903295 TI - Debate please, Mr Caines. PMID- 1903296 TI - Clear vision of nursing. Interview by Daniel Allen. PMID- 1903297 TI - Cot death: a family tragedy. PMID- 1903298 TI - During Drosophila embryogenesis the beta 1 tubulin gene is specifically expressed in the nervous system and the apodemes. AB - We determined the in vivo distribution of the beta 1 tubulin from D. melanogaster using isotype specific antibodies. Maternally expressed beta 1 tubulin is incorporated into mitotic spindles. Later in development a strong expression in the CNS is observed. Furthermore, all chordotonal organs and the apodemes are marked by beta 1 tubulin. Nuclear run-on assays and stage specific in vitro transcription showed a zygotic expression of the beta 1 tubulin gene from the extended germ-band stage onwards. Using the P-element system, we identified several elements; upstream between -2.2 kb and the transcription initiation site, elements for low level expression in the CNS are present. In the intron between +0.44 kb and +2.5 kb enhancer elements are located that drive the expression in the chordotonal organs and the apodemes. Between the start site and +0.44 kb (273 bp) and +2.5 kb and the second exon (315 bp), maternal and CNS enhancers result in full level expression of a lacZ-beta 1 reporter gene. We show, that the beta 1 tubulin gene is very early effector gene starting its expression shortly after the commitment of neuroblast cell fate. This gene offers an excellent model system for the identification of neural and apodeme specific transcription factors. PMID- 1903300 TI - Severe late intestinal complications after abdominal and/or pelvic external irradiation with high energy photon beams. AB - A total of 264 patients were treated between January 1981 and December 1985 for abdominal and/or pelvic tumours with high energy photon beams. Pelvic irradiation encompassed the true pelvis with upper limit located at the L5-S1 junction for 126 patients, at the L4-L5 junction for 107 patients with only 31 patients receiving external irradiation with treatment fields extending up to T12. The dose delivered to the pelvis was in the range 40-50 Gy with 72 (27.27%) patients receiving an extra dose on limited volumes up to 60-65 Gy. Acute intestinal reactions were observed in 38 (14%) patients. Using the Chassagne grading, we observed 14 grade 1,9 grade 2,13 grade 3 and 2 grade 4 late intestinal complications. Incidence of severe late intestinal complications in our series was 5.67% (15/264). Among these 15 patients three died of progression of the disease outside the treated volume, two died because of intestinal complications and/or their treatment and two died of unknown reasons. The remaining eight patients are alive with no evidence of the disease but with marked impairment of their intestinal functions. The analysis of risk factors showed only previous surgery (with laparotomy) to be significant, whereas age, delivered dose and treatment field and marked obesity had no influence on incidence of severe late intestinal complications. PMID- 1903299 TI - Effects of propionate on mechanical and metabolic performance in aerobic rat hearts. AB - The purpose of this report is to describe the contribution of propionate as an adjunct source of oxidative metabolism in aerobic myocardium. In the first series of studies, six groups of isolated working rat hearts (n = 6-8 per group) were perfused for 40 minutes with Krebs-Henseleit media containing 11 mM glucose. Propionate treatment was provided to the media at a constant dose per heart group and extended over a range of dosages, including: 0 (placebo control), 0.1, 0.5, 1.0, 5.0, and 10.0 mM, buffered to pH 7.4. Average aerobic coronary blood flow for all groups was 21.5 +/- 0.6 ml/min; average left ventricular peak systolic pressure was 123.7 +/- 1.4 mmHg. There were no significant differences among groups compared with placebo hearts for aortic flow, heart rate x aortic pressure product, or myocardial oxygen consumption, although performance tended to decline in the 10 mM group. A clear dose-response relationship was observed in 14CO2 production from labeled propionate, with a 12-fold increase between the 0.1 and 10 mM groups. Most of the increase occurred at the lower dosages, with a relative leveling off at the 1.0, 5.0, and 10.0 mM doses. In part 2, propionate was examined as a sole substrate. At 1.0 mM without glucose, propionate per se was unable to support mechanical function over the course of the perfusions, but still maintained high rates of oxidation, comparable to that of the 1.0 mM group with glucose in part 1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1903301 TI - Cost efficiency of bone scans in breast cancer. AB - A total of 110 consecutive females who presented in 1987 with primary carcinoma of the breast were staged according to the UICC TNM staging system. Of these, 90 patients had bone scans at presentation, of which seven were positive. The rate of positive initial scans for Stages I-II was 3.5%. Of these only one patient subsequently had bone metastases confirmed, to diagnose which by bone scan, the estimated cost was pounds 1300. Follow-up information was obtained for 95 patients, repeat scans being performed in 22 who had symptoms suggestive of bone metastases. Ten patients with negative initial scans converted to scan-positive within a mean time of 15 months. Only four of these had radiological confirmation of bone metastases. The cost of detecting bone metastases by follow-up scan was approximately pounds 80 per patient. The false-positive rate and the false negative rate were both calculated as 10%. The specificity of the test was calculated as 90%. It is recommended that bone scanning should be reserved for patients with Stages III and IV disease and to evaluate symptoms suggesting bone metastases. PMID- 1903302 TI - Extracorporeal membrane oxygenation in a European center--clinical experience. AB - Extracorporeal membrane oxygenation (ECMO) has rapidly become the treatment of choice for critically ill newborn infants with reversible pulmonary disease refractory to conventional treatment. Since 1987 ECMO has been available at our hospital and up to December 1989 11 patients have been treated. Eight patients could be weaned from ECMO. The aim of this study was to describe the procedure and its implications in the neonatal and pediatric age groups and to present our experience. It is concluded that even though ECMO in the short term is a costly and personnel-consuming procedure it is well documented, safe and life-saving. PMID- 1903303 TI - Sensitization to OKT3 monoclonal antibody in heart transplantation: correlation with early allograft loss. AB - Because administration of murine monoclonal anti-CD3 antibody (OKT3) may result in the formation of human antimouse antibody, which complexes with OKT3, we conducted this study to assess the incidence and effect of human antimouse antibody formation during prophylactic administration of OKT3 in heart transplantation. Human antimouse antibody developed in eight of 55 (14%) cardiac allograft recipients receiving OKT3 prophylaxis as measured by enzyme-linked immunosorbent assay. Additionally, two recipients had an inexplicable rise in CD3+ lymphocytes during therapy without detectable antibody. The outcome of these 10 sensitized recipients was compared with that of 45 nonsensitized recipients. Age, preoperative diagnosis, hemodynamics, and the need for intravenous inotropes or mechanical assistance before transplantation were similar in both groups. No female patients were in the sensitized group, whereas 33% of the nonsensitized group were female patients. A trend toward greater sensitization when prophylaxis was extended to 21 days (28%) compared with the more conventional 14-day administration (10%) was not statistically significant. Retransplantation because of rejection was required in a single patient in each group. Allograft survival was significantly lower by 3 months in the sensitized group, and allograft loss caused by rejection selectively accounted for that difference. In survivors, rejection frequency and infectious complications were similar. These findings suggest that sensitization to OKT3 occurs at low frequency after prophylactic administration in heart transplantation but is associated with an increased frequency of graft loss because of rejection. PMID- 1903304 TI - Prostaglandin endoperoxide synthase: structure and catalysis. PMID- 1903305 TI - C20 polyunsaturated fatty acids and phorbol myristate acetate enhance agonist stimulated synthesis of 1-radyl-2-acetyl-sn-glycero-3-phosphocholine in vascular endothelial cells. AB - This study has investigated the effect of supplementation of vascular endothelial cells with arachidonate and other polyunsaturated fatty acids on the agonist stimulated synthesis of platelet activating factor (PAF; 1-O-alkyl-2-acetyl-sn glycero-3-phosphocholine; 1-alkyl-2-acetyl-GPC). Incubation of calf pulmonary artery endothelial cells for 48 h in medium containing 40 microM arachidonate resulted in a 2-3-fold enhancement of [3H]acetate incorporation into 1-radyl 2[3H]acetyl-GPC in response to either bradykinin or calcium ionophore A23187. The effects of arachidonate supplementation were both dose- and time-dependent, requiring a minimum exogenous arachidonate concentration of 2.5 microM and an incubation time of 4-6 h. Eicosapentaenoate and docosahexaenoate also enhanced the synthesis of 1-radyl-2-[3H]acetyl-GPC, but were less potent than arachidonate; alpha-linolenate, linoleate and oleate were without effect. Although not effective as an agonist, phorbol myristate acetate potentiated A23187- and bradykinin-stimulated synthesis of 1-radyl-2-[3H]acetyl-GPC. The effects of arachidonate supplementation were synergistic with potentiation by phorbol myristate acetate. Sphingosine inhibited agonist-stimulated incorporation of [3H]acetate into 1-radyl-2-[3H]acetyl-GPC both in the presence and absence of PMA. Characterization of the radiolabeled material indicated that the primary product was the acyl analogue of PAF (1-acyl-2-acetyl-GPC) rather than PAF. The results from this study suggest that agonist-stimulated synthesis of 1-radyl-2 acetyl-GPC in vascular endothelial cells is modulated both by cellular fatty acyl composition and activation of protein kinase C. Enrichment of vascular endothelial cells with fatty acids, which are mobilized by agonist-stimulated phospholipase A2, may enhance subsequent deacylation of choline phospholipids and, thus, increase synthesis of both 1-acyl-2-acetyl-GPC and PAF. PMID- 1903306 TI - Ethical dilemmas: a case study. AB - Although the governing of medical conduct has always existed, medical ethics has become an issue to be addressed in the 1990s. The purpose of this article is to address the dilemma of reinserting a feeding tube in a patient whose wishes are unclear and whose family and physicians are in conflict. By presenting a case study, the author encourages the reader to resolve this dilemma on a personal level. PMID- 1903307 TI - Structure and nucleotide sequence of the Bacillus subtilis phenylalanyl-tRNA synthase genes. PMID- 1903308 TI - RNA binding by the tat and rev proteins of HIV-1. AB - HIV-1 tat protein binds specifically to HIV-1 TAR RNA. A Scatchard analysis of tat binding has shown that the purified protein forms a one-to-one complex with HIV-1 TAR RNA with a dissociation constant of Kd = 12 nM. Tat binding in vitro is dependent upon the presence of 3 non-base paired U residues which produce a 'bulge' in the TAR RNA stem-loop structure. Deletion of the uridine residues in the bulge or substitution with guanine residues produced RNAs with a 6 to 8-fold lower affinity than wild-type TAR. By contrast, mutations that alter the sequence of the 6 nucleotide-long loop at the tip of TAR RNA structure, and mutations which alter the sequence of the stem whilst preserving Watson-Crick base pairing, do not affect tat binding significantly. There is a direct correlation between the ability of tat to bind to TAR RNA and to activate HIV transcription. Viral LTRs encoding TAR sequences known to bind tat weakly, are not stimulated efficiently by tat in vivo. HIV-1 regulator of virion expression (rev) protein binds specifically to RNA transcripts containing the 223 nucleotide-long RRE sequence with an apparent dissociation constant of 1-3 nM. The minimum binding site for rev is a 'bubble' containing 2 G residues on one side and the sequence AGU on the other. Rev is able to bind efficiently to this restricted site in the context of the RRE sequence as well as in the context of a stable RNA duplex with a sequence unrelated to that found in the RRE.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1903309 TI - Acute hematologic effects of interferon alpha, interferon gamma, tumor necrosis factor alpha and interleukin 2. AB - This study was designed to investigate acute effects of various doses of the cytokines IFN-alpha, IFN-gamma, Interleukin 2 and tumor necrosis factor alpha on white blood cell differential counts. Before initiation of phase II trials, a dose-determination phase was performed, where three different dose levels of each cytokine were applied as a single dose. White blood cell differential counts were assessed immediately before and 2, 12, 24, 48 and 168 h after injection. Patients enrolled suffered from metastatic cancer or chronic active hepatitis. In addition, IFN-alpha was administered to five healthy volunteers. Results indicate that cytokines cause rapid and transient changes in the numbers of leukocyte subsets. Hematologic changes were cell-type- and cytokine-specific: transient lymphopenia was observed after administration of all four cytokines, reaching a nadir 12 to 24 h after subcutaneous injection. Administration of TNF-alpha and IFN-gamma also caused transient monocytopenia. Neutrophilia developed after administration of Interleukin 2, IFN-alpha and TNF-alpha. We conclude that cytokines play a key role in the regulation of peripheral blood cell traffic by their capacity to influence homing patterns of peripheral blood leukocytes. PMID- 1903312 TI - Spontaneous interferon-alpha antibodies in a patient with pure red cell aplasia and recurrent cutaneous carcinomas. AB - High-titered spontaneous interferon (IFN) antibodies were detected in a patient with pure red cell aplasia (PRCA), a benign mediastinal tumor, and recurrent cutaneous carcinomas. The circulating IFN antibodies reacted broadly with various human IFN-alpha subtypes (20-140 x 10(3) neutralizing units/ml serum) but not with IFN-beta or IFN-gamma, and they neutralized the antiviral activity of the patient's endogenous IFN-alpha. The IFN-alpha-binding activity was restricted to the IgG1 subclass in a nonmonoclonal manner. Whereas the PRCA repeatedly responded to immunosuppression with high-dose cyclosporin A (CSA) and CSA plus plasmapheresis, IFN antibody production continued during treatment with cyclophosphamide and CSA. Serological analysis revealed past infection with parvovirus B19 and persistent B19 IgM titers. Antibody-mediated impairment of the IFN-alpha system might have favored the development of both PRCA and the various cutaneous carcinomas in this patient. PMID- 1903311 TI - C8 binding protein bears I antigenic determinants. AB - C8 binding protein (C8bp) is an integral membrane glycoprotein of peripheral blood cells, which inhibits the C5b-9-mediated lysis in a homologous system. In the present study, we analyzed the carbohydrate portion of the C8bp. We found that C8bp is associated with I antigenic determinant, a sugar sequence found on human erythrocytes of adults. To assess whether or not the sugar residues are essential for the C8bp function, I determinant was cleaved off from the isolated C8bp by endo-beta-galactosidase (E.C. 3.2.2.103) that hydrolyses internal beta galactosidic-linked-N-acetyllactosamine residues. Enzyme treatment removed I antigen, the inhibitory function of C8bp, however, was not affected. When intact erythrocytes were treated with endo-beta-galactosidase, I-antigen was lost and the lytic insusceptibility of human erythrocytes to homologous C5b-9 could not be abolished. Thus, I-antigen is associated with the C8bp, but its presence is not required for the homologous species restriction. PMID- 1903313 TI - Intranasal fractionated administration of desamino-D-arginine vasopressin (DDAVP) in patients with von Willebrand's disease. PMID- 1903310 TI - Hemophilia treatment in historical perspective: a review of medical and social developments. PMID- 1903314 TI - Organochlorine insecticide and polychlorinated biphenyl residues in martens and fishers from the Algonquin Region of south-central Ontario. PMID- 1903315 TI - Fate of 14C-carbaryl in soils as a function of pH. PMID- 1903316 TI - GPs and long term mentally ill patients. PMID- 1903317 TI - Results of a recently instituted programme of thrombolytic therapy in acute lower limb ischaemia. AB - Twenty-eight patients with acute lower limb ischaemia received low dose intra arterial thrombolytic therapy over a 2-year period. Eighteen patients received streptokinase and ten patients received recombinant tissue plasminogen activator (rTPA). Indications included arterial thromboemboli and graft failures. Mean ischaemic times were similar in both groups. Treatment time to achieve lysis was significantly less with rTPA (P less than 0.01). Subsequent vascular procedures, including angioplasty or reconstruction, were undertaken in 36 per cent of patients. Arterial puncture site bleeding occurred in eight (29 per cent) patients. Three (11 per cent) patients suffered rethrombosis after initial successful lysis. All rethromboses were successfully lysed with rTPA. There were two major amputations. Five (18 per cent) patients died, all lytic failures in the streptokinase treatment group. There were no cerebral haemorrhagic events and no patient died as a result of thrombolytic therapy. Good clinical outcome was obtained in nine of 18 patients treated with streptokinase and in nine of ten patients treated with rTPA. Intra-arterial thrombolysis provides effective therapy with high rates of limb salvage and a low mortality rate. This study suggests that rTPA may be a more effective agent, causing less morbidity, than streptokinase. PMID- 1903318 TI - Selective uptake of glutamine in the gastrointestinal tract: confirmation in a human study. AB - Recent animal data suggest that the gut plays a far more important metabolic role than previously thought. During critical illness, disruption in bowel barrier function may result in a chronic hypermetabolic state and contribute to multiorgan failure. Animal studies have demonstrated that enterocytes of the gastrointestinal tract use glutamine as a respiratory fuel and during critical illness the consumption of glutamine by the gut significantly increases. The selective uptake of glutamine by the gut, to date, has not been confirmed in humans. Seven patients who sustained multisystem trauma necessitating laparotomy underwent portal venous catheterization. This was done by carefully reopening the obliterated umbilical vein and facilitating access to the left branch of the portal vein using a standard central venous catheter. Portal venous and systemic blood samples were recorded for 5 days after operation. Amino acid levels in both circulations were recorded at 48 h and 5 days. Using Student's t test for related samples, the differences between individual amino acids in portal and systemic circulations were compared. At 48 h, mean(s.d.) portal venous glutamine was 85(5) per cent of the systemic levels (253(80) compared with 296(90) mumol/ml, P less than 0.002). At 5 days, portal glutamine was 87(3) per cent of the systemic levels (255(69) compared with 292(83) mumol/ml, P less than 0.003). Levels of citrulline, a breakdown product of glutamine metabolism, were elevated in the portal venous circulation at 48 h (20(4) compared with 16(3) mumol/ml, P less than 0.005) and at 5 days (21(5) compared with 14(3) mumol/ml, P less than 0.002). No significant differences between any of the other amino acids analysed were identified. This study confirms, for the first time in humans, that selective uptake of glutamine occurs in the gut. In stressed states, glutamine deficiency is associated with gut mucosal atrophy. This has significant implications as glutamine is not provided in most commercially available parenteral and enteral nutrition formulations. PMID- 1903319 TI - Stimulation of protein synthesis in human tumours by parenteral nutrition: evidence for modulation of tumour growth. AB - Eighteen patients with localized colorectal carcinoma were randomized to receive intravenous nutrition or to be fasted during the 24 h before surgery. Protein synthesis, an index of tumour growth, was then measured by the incorporation of [13C]leucine into tumour protein immediately before surgery. The mean (s.e.m.) rate of tumour protein synthesis in patients receiving nutrition (42.7(3.5) per cent per day) was 89 per cent higher than the rate in the fasted group (22.6(1.9) per cent per day) (P = 0.002). As tumours consist of a variety of different cell types, in vitro rates of protein synthesis were measured in malignant cells isolated from colorectal tumours and cultured with autologous serum obtained from the patient in either the fasted or the fed state. There was a mean increase of 81 per cent in protein synthesis when fed rather than fasted serum was used (P less than 0.02), indicating that the malignant cells themselves respond to nutrient supply. This increase in tumour protein synthesis provides the first evidence in vivo that the exogenous supply of nutrients can modulate the rate of growth of a human tumour. PMID- 1903320 TI - Carbon dioxide laser ablation of cutaneous metastases from malignant melanoma. AB - Multiple cutaneous and superficial subcutaneous metastases from malignant melanoma in 30 patients were treated palliatively by carbon dioxide laser ablation when lesions were to numerous, too large or recurring too rapidly for multiple local excisions. The number of lesions per patient ranged from three to 250 (median 30). Patients were treated under local or general anaesthetic and as day cases or inpatients. After a median follow-up interval of 8 months fewer than 1 per cent of lasered metastases have recurred locally. Sixteen patients have developed cutaneous metastases at other sites requiring further treatment. Approximately 2000 lesions have been treated on 64 occasions. Patients reported little or no pain after the operation and required only simple dry dressings. Wounds were completely healed in 2-6 weeks with good cosmetic results. This simple and effective treatment is becoming an alternative to isolated limb perfusion. PMID- 1903322 TI - [Life Sciences-Series III. Book reviews of the Academy of Sciences. No. 13-Volume 311. July-December 1990]. PMID- 1903321 TI - Carbon dioxide insufflation in gastrointestinal surgery. PMID- 1903323 TI - Molecular genetics of human immune responsiveness to pollen allergens. PMID- 1903324 TI - The IgE response in atopy and infections. PMID- 1903325 TI - [Preliminary investigation of effect of pyocyanin on common bacteria in burn wound]. AB - Pyocyanin was extracted from culture medium of Ps. aeruginosa by Frank's method. Minimum inhibitory concentration (MIC) & minimum bactericidal concentration (MBC) of pyocyanin for 6 species of bacteria isolated from burn wounds were determined. The results of MIC & MBC: S. aureus 12.5 micrograms/ml, 50 micrograms/ml; E. coli 25 micrograms/ml, 100 micrograms/ml; P. vulgaris 50 micrograms/ml, 200 micrograms/ml; C. freundii 100 micrograms/ml, 400 micrograms/ml; S. epidermidis 12.5 micrograms/ml, 50 micrograms/ml; no inhibitory effect on Ps. aeruginosa. According to the laboratory results and clinical findings, the authors believe that when there is a dominant growth of Ps. aeruginosa in burn wounds there may be pyocyanin production to inhibit or kill other species of bacteria. PMID- 1903326 TI - Absolute configuration of 7,12-dimethylbenz[a]anthracene-DNA adducts in mouse epidermis. AB - 32P-Postlabeling was used to monitor the formation of DMBA-DNA adducts in mouse epidermis from each enantiomer of the trans 3,4-dihydrodiol. It was shown that the (4R,3R)-dihydrodiol is converted to the anti (4R,3S)-dihydrodiol (2S,1R) epoxide which reacts with deoxyguanosine and deoxyadenosine residues in epidermal DNA to yield two of the major adducts formed when DMBA itself binds to epidermal DNA. The third major DMBA-derived adduct with deoxyadenosine residues was shown to arise from the (4S,3R)-dihydrodiol through the intermediacy of the syn (4S,3R) dihydrodiol (2S,1R)-epoxide. PMID- 1903327 TI - Effect of dietary arginine restriction upon ornithine and polyamine metabolism during two-stage epidermal carcinogenesis in the mouse. AB - Polyamine synthesis is required in normal or neoplastic tissues if they are to continue to grow or divide. The highly inducible enzyme ornithine decarboxylase (ODC) catalyzes the conversion of ornithine to putrescine as the initial step in polyamine biosynthesis. The level of substrate pools of ornithine in cultured cells has been reported to markedly alter mitogen-induced ODC activity, putrescine accumulation, and DNA synthesis (V. Wu and C. V. Byus, Biochim. Biophys. Acta, 804: 89-99, 1984; V. Wu et al., Cancer Res., 41: 3384-3391, 1981). We attempted to limit the amount of ornithine available for polyamine biosynthesis in an animal by using a dietary approach. Since arginine serves as one of the intermediate biosynthetic precursors of ornithine, female CD-1 mice were placed on a special synthetic amino acid diet deficient in arginine. The ability of this arginine-free diet to alter epidermal ornithine and polyamine metabolism and tumorigenesis was assessed in the mouse two-stage model of skin carcinogenesis. The basal level of ornithine in the epidermis in control animals receiving the amino acid complete diet was very high compared to other tissues (155 nmol/mg protein). However, when the mice were fed the isocaloric arginine free diet for a 2-week period, the levels of epidermal ornithine and arginine decreased by 40% (P less than 0.01). This reduction was blocked by the addition of 2% ornithine to the drinking water of the arginine-restricted animals. Acute administration of 12-O-tetradecanoyl-phorbol-13-acetate (TPA) to the epidermis caused a transient (4 and 8 h) reduction in ornithine and arginine but not lysine in the animals receiving the control, and ornithine-supplemented diets. The animals fed the special arginine-free diet exhibited a 40-50% reduction in tumor multiplicity or papillomas/mouse (P less than 0.05) and had a significantly lower tumor incidence or percentage of animals with tumour throughout a 19-week promotion period (P less than 0.02). However, the major effect of arginine restriction was consistent with an increase in tumor latency. The addition of ornithine completely reversed the reduction in the rate and extent of tumorigenesis in the arginine-free animals. The accumulation of putrescine (but not spermidine or spermine) in the epidermis following a single administration of TPA was significantly reduced in the animals receiving the arginine-free diet. The papillomas or tumors from the animals deprived of arginine had markedly reduced (less than 35%) levels of putrescine compared to the tumors from control animals, and appeared to be more sensitive to dietary arginine restriction than was the chronically promoted but untransformed epidermis.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1903328 TI - Role of postreplication repair in transformation of human fibroblasts to anchorage independence. AB - Cellular capacity for postreplication repair (PRR) and sensitivity to transformation to anchorage independence (AI) were quantified in normal foreskin and xeroderma pigmentosum (XP) variant fibroblasts after treatment with UV or benzo(a)pyrene-diol-epoxide I (BPDE-I). PRR is defined here as a collection of pathways that facilitate the replication of DNA damaged by genotoxic agents. It is recognized biochemically as the process by which nascent DNA grows longer than the average distance between two lesions in the DNA template. PRR refers more directly to the elimination of gaps in the daughter-strand DNA by mechanisms which remain to be determined for human cells, but which may include translesion replication and recombination. PRR was measured in diploid human fibroblasts by analysis of the dose kinetics for inhibition of DNA strand growth in carcinogen treated cells. Logarithmically growing foreskin fibroblasts (NHF1) displayed D0 values of 4.3 J/m2 and 0.14 microM for the inhibition of DNA synthesis in active replicons by UV and BPDE-I, respectively. XP variant cells (CRL1162) exhibited corresponding D0 values of 1.5 J/m2 and 0.16 microM. The increased sensitivity to inhibition of DNA replication by UV in these XP variant fibroblasts (2.9-fold greater than normal) was mirrored by an enhanced frequency of transformation to AI. XP variant fibroblasts (CRL1162) were 3.2 times more sensitive to transformation to AI by UV than were the normal foreskin fibroblasts. As predicted by the PRR studies, both cell types exhibited similar frequencies of AI colonies induced by BPDE-I. Apparent thresholds were observed for induction of AI by UV (normal fibroblasts, 2.7 J/m2; XP variant fibroblasts, 0.3 J/m2) and BPDE-I (both, 0.05 microM). Doses of UV and BPDE-I above these thresholds produced proportional increases in the inhibition of DNA replication in operating replicons and in the induced frequency of anchorage-independent colonies. At doses of UV and BPDE-I that produced the same degree of inhibition of DNA strand growth, BPDE-I induced a greater number of cells capable of anchorage-independent growth than did UV in both normal and XP variant fibroblasts. PMID- 1903329 TI - [Costs and benefits of screening for colorectal tumors using the Hemoccult test in asymptomatic individuals 45-60 years of age]. AB - Screening of colorectal tumours by the Haemoccult test (HT) in asymptomatic subjects aged 45-60 years makes it possible to assess the diagnosis of colorectal carcinoma (CR-CA) in two-thirds of the affected subjects in Dukes stage A and B, as compared with one third of symptomatic patients of the same age group. The mean diagnostic and therapeutic costs related to the relative incidence of individual stages of Dukes staging of CR-CA in screened asymptomatic individuals and symptomatic patients are approximately equal. The analysis is not concerned with costs of care after surgical and supplementary treatment which are considerable in subjects with the advanced form of the disease. Its incidence is significantly higher in symptomatic patients. The mean expected productive age under 60 years is in symptomatic patients 2.604 years and in asymptomatic individuals 4.357 years. The mean national product assembled during this period is 468.720 Kcs and 784.260 Kcs resp. The difference in favour of one asymptomatic subject in the analyzed group is 38,495.880 Kcs. These facts fully justify further extension of screening programmes of CR-CA in our population. PMID- 1903330 TI - Transferrin receptors promote the formation of clathrin lattices. AB - Gold conjugates have been used to quantitate human transferrin receptors (hTfnRs) on transfected chick embryo fibroblasts. No relationship could be found between the number of hTfnRs and the number of clathrin-coated pits. However, hTfnRs are also associated with flat clathrin lattices that lie outside invaginated pits. With increasing levels of receptor expression, the density of hTfnRs within flat lattices increases, and at the highest levels of expression the total area of flat lattice increases up to 3-fold. These results show that increased receptor numbers can promote clathrin lattice growth and suggest that the recruitment of receptors like hTfnRs is an essential step in lattice construction. We conclude that the process of invagination, which gives rise to coated pits, is regulated separately. PMID- 1903331 TI - A point mutation in C-terminal region of cdc2 kinase causes a G2-phase arrest in a mouse temperature-sensitive FM3A cell mutant. AB - A mouse temperature-sensitive mutant for cell growth, tsFT210, was characterized. More than 90% of the mutant cells were arrested at the G2 phase at the nonpermissive temperature (39 degrees C). In this mutant, the activity of cdc2 kinase did not increase at the nonpermissive temperature (39 degrees C) but did increase at the permissive temperature (33 degrees C) at the G2/M phase in the cell cycle. The in vitro activity of cdc2 kinase of tsFT210 was more thermolabile than that of wild-type cells. The amount of cdc2 kinase in tsFT210 cells decreased when the cells were incubated at 39 degrees C, but that in wild-type cells did not. Using the polymerase chain reaction (PCR), a point mutation in cDNA of cdc2 kinase was found in tsFT210, and as a result, the proline of wild type cdc2 kinase at the 272 amino acid residues from N-terminal methionine changed to serine. During preparation of this paper, the detection of two mutation sites of this mutant was reported (Th'ng, J.P.H., Wright, P.S., Hamaguchi, J., Lee, M.G., Norbury, C.J., Nurse, P., and Bradbury, E.M. (1990). Cell, 63: 313-324); one was the same site as reported here, the other was A-to-G change in the 154th base from base A in initial ATG, and this caused the change of isoleucine to valine in the PSTAIR region of cdc2 kinase. This mutation in the PSTAIR region was not detected by us. The probable reason for this discrepancy was in that Th'ng and his group sequenced a cDNA cloned from the amplified cDNAs by PCR, and did not directly sequence the amplified cDNA as we did. PMID- 1903332 TI - Heat shock induced ultrastructural alterations in Stylonychia mytilus cells. AB - Fine structural observations on heat shocked cells of S. mytilus reveal that cell organelles undergo structural alterations. Mitochondria show distorted shapes with disorganized cristae and vacuolar spaces. Pulse heat shock results in dilated rough endoplasmic reticulum, abundant polysomes as well as smooth endoplasmic reticulum. Heat shocked cells show membrane bound bodies containing osmiophilic cores. In macronuclei, dense chromatin breaks up into discrete bodies accompanied by the appearance of bundles of fine filaments and clustering of nuclear pores. The most prominent changes are noticed in nucleoli. Within 15 min of heat shock, nucleoli show hypertrophy and fine fibrillar zone which gradually replaces the granular zone by 120 min giving the nucleoli ring shaped configuration. In S phase cells, macronuclei show the arrested replication band in which the diffused zone (the site of DNA replication) is absent. PMID- 1903333 TI - Influence of monoclonal immunoglobulins in direct determinations of iron in serum. AB - I compared seven buffers and four chromogens for determining serum iron, to evaluate the frequency of falsely high or low concentrations of iron in 59 sera containing monoclonal immunoglobulins. The results for these direct assays with untreated sera were compared with those obtained by a proposed reference method (Br J Haematol 1978;38:291-4) with protein-free filtrates of the same sera. Sera with monoclonal immunoglobulins sometimes yielded erroneous results; the frequency of errors, which could be as much as 29% (17/59), depended on the composition of buffer and color reagent. Addition of thiourea or a detergent (Triton X-405) to some of the buffers lowered the frequency of errors, but did not abolish them. In only a few of the investigated buffer/chromogen combinations were no errors found. Detection of errors by analyzing the absorbance pattern after mixing sample and buffer was not always successful. Moreover, the presence and magnitude of errors bore no relationship to the type or the concentration of the monoclonal immunoglobulins. Unfortunately, the problem cannot be solved by a simple two- or threefold dilution of the sample. PMID- 1903334 TI - Immunoturbidimetric method for routine determinations of apolipoproteins A-I and B. AB - A simple immunoturbidimetric method for quantifying apolipoproteins (apo) A-I and B in serum or plasma is described. A special reagent formulation, including large amounts of suitable detergents, obviates the need for a sample blank even with grossly lipemic specimens. The assay is rapid, easily automated, and thus convenient for routine work. For both apo A-I and apo B, the assay range is about 0.2-3.5 g/L. The performance characteristics were assessed with discrete (Optimate and Olli CD) and centrifugal analyzers (Cobas Fara and IL Monarch 2000). Average analytical recovery was 101.5% for apo A-I and 99.4% for apo B. Dilution tests showed found/expected ratios of 101.2% (apo A-I) and 101.0% (apo B). Overall precision (CV) ranged from 1.4% to 3.3% for apo A-I and from 1.1% to 8.3% for apo B. Comparisons with commercially available rate nephelometry, radial immunodiffusion, and immunoturbidimetric methods gave good correlations (r greater than or equal to 0.938). Using the immunoturbidimetric method, we also established the relationships between apolipoproteins and lipids and determined the reference intervals. We conclude that the proposed method is suitable for routine use in clinical laboratories. PMID- 1903336 TI - Trial of flecainide acetate in the management of tinnitus. AB - A two-phase trial of flecainide acetate in the management of tinnitus has been carried out in 22 patients with severe long-term tinnitus resistant to other treatments. Although 5 (23%) patients reported some limited benefit the results are not conclusive but suggest that, for such patients, flecainide deserves a place as a drug worth considering as a last resort, with the prospect of it occasionally giving a worthwhile degree of relief. PMID- 1903337 TI - IgA nephropathy: characterization of the light chain. PMID- 1903335 TI - Crossover phenomena in epileptic syndromes of childhood. AB - Benign Rolandic epilepsy (BRE) and primary generalized epilepsy (PGE) are found at about the same period of childhood. Crossover from PGE to BRE and vice versa may occur; two short case reports provide further evidence for this development. Hence, transitions from a primarily generalized to a focal (partial) epileptic seizure disorder and vice versa is a possibility. Both PGE and BRE are based upon states of hyperexcitability, i.e. dysfunctional rather than structural abnormalities that are capable of changing their spatial distribution. PMID- 1903338 TI - 'Surgical parotitis' demonstrated by Ga-67 scintigraphy in critically ill patients. PMID- 1903339 TI - Criteria for use of misoprostol. PMID- 1903340 TI - Antimicrobial activity of subinhibitory concentrations of aminoglycosides against Pseudomonas aeruginosa as determined by the killing-curve method and the postantibiotic effect. AB - This investigation used the postantibiotic effect (PAE) and killing curves to provide data on the antimicrobial activity of subinhibitory (1/8x, 1/4x and 1/2x minimum inhibitory concentration; MIC) and inhibitory (1x MIC) concentrations of amikacin, gentamicin and tobramycin against Pseudomonas aeruginosa. Subinhibitory concentrations (1/4x and 1/2x MIC) of aminoglycosides demonstrated a reproducible PAE. At 1/4x MIC, the order of duration of the PAE was approximately 15 min for all aminoglycosides, while at 1/2x MIC all three aminoglycosides displayed a similar PAE of approximately 40 min. Killing-curve studies demonstrated that subinhibitory concentrations of aminoglycosides either decrease bacterial growth for several hours (1/4x and 1/2x MIC) or produce stasis of growth for several hours (1/8x MIC). Only inhibitory aminoglycoside concentrations (1x MIC) proved to be bactericidal. Subinhibitory concentrations of aminoglycosides decrease bacterial growth and produce a PAE against P. aeruginosa. PMID- 1903341 TI - In vitro activity of ceftriaxone and amikacin against Pseudomonas aeruginosa. AB - Ceftriaxone and amikacin were combined at ratios of 1:1, 5:1, and 10:1 and tested in vitro against Pseudomonas aeruginosa. The activity was determined using the Steers-Foltz replicator and the agar dilution technique with Mueller-Hinton agar. Under all conditions tested, including those simulating severe infection (10(5) to 10(6) colony-forming units per spot), the organisms were more susceptible to the combination than to the single agents. With a conventional inoculum of 10(4) colony-forming units per spot, the combinations gave 97-100% coverage against P. aeruginosa. The increased activity of the combinations resulted in MIC90 values which were below the expected serum/plasma levels for significantly longer time periods than the MIC90 values observed with the individual agents. PMID- 1903343 TI - Intensive liver care and management of acute hepatic failure. AB - In describing acute liver failure, the term fulminant hepatic failure (FHF) is used to denote patients with the most rapid progression, normally defined as the onset of encephalopathy within eight weeks of the onset of symptoms. For patients with a slower onset of encephalopathy, ranging from eight weeks to six months after the onset of symptoms, late-onset hepatic failure is the term used to reflect the overlap in clinical features with some patients with FHF. The importance of accurately determining the type of acute liver failure results from increasing evidence of an inverse relationship between the tempo of disease progression and the chances of recovery. Prognosis is also dependent on the underlying etiology. Principles of management are as follows: (1) an accurate recognition of the tempo of the hepatic failure--fulminant, late onset, acute on chronic--and the establishment of a likely etiology; (2) early detection and treatment of complications, particularly metabolic acidosis (early), renal failure, cerebral edema, and infection (late); (3) optimization of conditions for regeneration by maintenance of a near normal metabolic milieu (with removal of toxins by various methods of artificial liver support if necessary); and (4) early consideration of an orthotopic liver transplant for those patients in the poor prognosis group. Variations in the natural history and clinical features of acute liver failure (ALF) have led to a number of different classifications and subgroupings. Knowledge of these is important in relation to the assessment of prognosis and is even more important now that transplantation is a therapeutic option.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1903342 TI - Treatment of fulminant viral hepatic failure with prostaglandin E. A preliminary report. AB - The effect of prostaglandins (PG) in patients with fulminant and subfulminant viral hepatitis was studied. Seventeen patients presented with FHF secondary to hepatitis A (N = 3), hepatitis B (N = 6) and non-A, non-B (NANB) hepatitis (N = 8). Fourteen of the 17 patients had stage III or IV hepatic encephalopathy (HE). At presentation, the mean AST was 1844 +/- 1246 units/liter, bilirubin 232 +/- 135 mumol/liter, PT 34 +/- 18 and PTT 73 +/- 26 sec, and coagulation factors V and VII were 8 +/- 4 and 9 +/- 51%, respectively. Twelve of 17 patients responded to PGE1 rapidly, with a decrease in AST from 1540 +/- 833 to 188 +/- 324 units/liter, a decrease in prothrombin time from 27 +/- 7 sec to 12 +/- 1 sec, PTT from 61 +/- 10 sec to 31 +/- 2 sec, and an increase in factor V from 9 +/- 4% to 69 +/- 18% and factor VII from 11 +/- 5% to 71 +/- 20%. Five responders with NANB hepatitis relapsed upon discontinuation of therapy, with recurrence of HE and increases in AST and PT but improvement was observed upon retreatment. After four weeks of intravenous therapy, oral PGE2 was substituted. Two patients have recovered completely and remain in remission six and 12 months following cessation of therapy. Two additional patients continue in remission after two and six months of PGE2. No relapses have been seen in patients with hepatitis A virus (HAV) or hepatitis B virus (HBV) infection. Liver biopsies in the 12 surviving patients have returned to normal. These results suggest efficacy of PGE for FHF. Further investigation is warranted. PMID- 1903345 TI - Infection control and office safety. PMID- 1903344 TI - [Therapy-refractory fulminant meningococcal sepsis]. AB - Two cases of the severe form of meningococcal infection are described. A 17-year old girl and a (unrelated) 2-year-old boy suddenly developed fever and rigor. Several hours later petechiae of the skin were noted: they rapidly spread. On admission the girl was found to have a severe consumptive coagulopathy (prothrombin 24%, partial thromboplastin time 104 sec, fibrinogen 73 mg/dl, platelets 35,000/microliters). She died two-and-a-half hours after admission of treatment-resistant shock. The boy had at first only a low prothrombin value (39%), but later the other coagulation values also became abnormal. He died 16 hours after admission from the consumptive coagulopathy and profound anaemia (haemoglobin 7.4 g/dl, haematocrit 0.23). Neither patient had any clinical signs of meningitis. Isolation of Neisseria meningitidis from blood cultures confirmed the diagnosis. PMID- 1903346 TI - A within-patient comparison between superovulation with intra-uterine artificial insemination using husband's washed spermatozoa and gamete intrafallopian transfer in unexplained infertility. AB - The purpose of this study was to evaluate the success of gamete intrafallopian transfer (GIFT) and superovulation with intra-uterine artificial insemination (S IUI) in couples with long-term unexplained infertility. Thirty-nine couples were offered three attempts at each treatment. Sixty-three IUI cycles were completed with a pregnancy rate of 1.5% per cycle. Forty-nine GIFT procedures were carried out with a pregnancy rate of 26.5% per cycle. The cumulative conception rate after three cycles of GIFT was 0.56. GIFT appears to offer a far greater chance of pregnancy than S-IUI in unexplained infertility. PMID- 1903347 TI - Pregnancy following regression of uterine submucosal leiomyoma with GnRH therapy; a case report. AB - A patient with a history of two spontaneous abortions, at the 16th and 20th week, respectively, and one intra-uterine fetal death at the 26th week of gestation was investigated. The sole abnormal condition that could be evidenced was a submucosal leiomyoma of 56 mm in diameter in the uterine fundus. Administration of gonadotropin/releasing hormone analog (GnRHa) for 10 months resulted in complete disappearance of myoma. Direct intraperitoneal insemination following induction of ovulation resulted in pregnancy. In a patient harboring uterine leiomyomas, adversely affecting conception and pregnancy outcome, GnRHa treatment may be an initial approach allowing to avoid pelvic surgery. As the beneficial effect of GnRHa might be temporary, assisted reproduction procedures might anticipate conception. PMID- 1903348 TI - Dysutility of endoscopic feeding tubes. PMID- 1903350 TI - Bacteriophage receptors of Lactococcus lactis subsp. 'diacetylactis' F7/2 and Lactococcus lactis subsp. cremoris Wg2-1. AB - Bacteriophage P008 revealed irreversible and uniform adsorption to cell walls of L. lactis subsp. 'diacetylactis' F7/2, whereas phage P127 adsorbed reversibly to a limited number of receptor sites on cell walls of L. lactis subsp. cremoris Wg2 1. Neither extraction of lipids, cell wall- and membrane-teichoic acids nor enzymatic degradation of proteins altered the binding efficiencies of both cell wall fractions. However, phage binding was inhibited, when cell walls were subjected to lysozyme, metaperiodate, or acid treatments. This reflects that a carbohydrate component embedded in the peptidoglycan matrix is part of the phage receptors of strains F7/2 and Wg2-1. PMID- 1903349 TI - Pyoverdine-mediated iron transport in Pseudomonas aeruginosa: involvement of a high-molecular-mass outer membrane protein. AB - Reduced expression of an iron-regulated outer membrane protein (IROMP) of approximate molecular mass 90,000 was observed in Pseudomonas aeruginosa concomitant with a loss of pyoverdine production in a wild type strain grown at 43 degrees C and in a mutant deficient in pyoverdine production. Consistent with an implied role in pyoverdine-mediated iron transport a mutant lacking the 90 kDa protein transported barely detectable levels of ferri-pyoverdine. Interestingly, the mutant still exhibited pyoverdine-dependent growth in an iron-deficient medium containing the synthetic iron chelator ethylene diamine-di(omicron hydroxyphenol acetic acid) (EDDHA) suggesting that a second uptake system for ferri-pyoverdine may exist in P. aeruginosa. PMID- 1903351 TI - Molecular screening of Clostridium difficile toxins A and B genetic determinants and identification of mutant strains. AB - Three separate sets of polymerase chain reaction primers were designed to specifically detect the presence of a toxin A gene fragment, a toxin B gene fragment, and the entire toxin B gene. In addition toxin gene fragments that were amplified from well characterized toxic strains were tagged fluorescently and used as hybridization probes to screen C. difficile strains. A survey of 37 toxic strains and 10 non-toxic strains demonstrated that toxic strains normally contain the genetic composition for toxin A and toxin B simultaneously; whereas, non toxic strains typically did not contain detectable toxin determinants. The only exception found was strain 39, which had the genetic composition for toxins A and B, but was not cytotoxic under the conditions tested. PMID- 1903352 TI - Respiratory activity in Listeria monocytogenes. AB - Listeria monocytogenes possessed glucose oxidase and NADH oxidase activities in whole cells and lysed protoplasts respectively. The NADH oxidase activity sedimented with the membrane fraction and was inhibited by the respiratory inhibitors rotenone, 2-heptyl-4-hydroxy-quinoline-N-oxide and cyanide, suggesting the presence of a membrane associated respiratory chain. PMID- 1903353 TI - Some properties of rat platelet aggregation and effects of butylated hydroxytoluene, warfarin and aspirin. AB - The platelet aggregation characteristics of male Sprague-Dawley (Jcl:SD) rats were investigated. Epinephrine, ristocetin, serotonin and platelet-activating factor were ineffective in rat platelets. Heparinized platelet-rich plasma (PRP) was more sensitive than citrated PRP to three aggregating agents, ADP, collagen and arachidonic acid. Butylated hydroxytoluene (BHT) and BHT quinone methide (2,6 di-tert-butyl-4-methylene-2,5-cyclohexadienone) inhibited ADP- and collagen induced aggregation at concentrations over 10(-3) M in vitro. The ADP-, collagen- and arachidonic acid (0.5-2.0 mM)-induced aggregations of PRP obtained from rats given 1.20% BHT in the diet for 7 days were normal, while arachidonic acid (3.9 mM)-induced aggregation of PRP from BHT-fed rats was significantly lower than control. PRP from rats given aspirin and warfarin also aggregated normally with ADP or collagen addition. These results suggest that heparinized PRP may be preferable in platelet aggregation analyses in rats and reaffirmed that effects on platelet aggregation may not play a key role in BHT-induced bleeding. Platelet aggregation capacity also does not necessarily reduce in haemorrhages induced by aspirin or warfarin. PMID- 1903354 TI - In situ production of interleukins in hyperplastic thymus from myasthenia gravis patients. AB - We analyzed by in situ hybridization the expression of four interleukin genes (interleukin-beta [IL-1 beta], IL-6, IL-2, and interferon-gamma) in seven thymuses displaying a follicular hyperplasia. The seven thymuses were obtained from patients with myasthenia gravis. Interleukin-1 beta- and IL-6-producing cells were detected in similar amounts and with similar distributions: mainly in perifollicular areas and in the connective structures emerging from the septae at the site of cortex disruption. The comparison of in situ hybridization and immunohistochemical results suggested that thymic epithelial cells and/or perifollicular macrophages were responsible for this production. Interleukin-2 producing cells were detected in perifollicular areas and, to a lesser extent, inside follicles. They were clearly outnumbered by CD25-positive cells which were similarly distributed. Despite the expression of these molecular and immunohistochemical markers of T-cell activation, interferon-gamma-producing cells were extremely rare in myasthenic thymuses. The pattern of interleukin production (which was virtually absent in normal control thymuses) in myasthenic thymuses was different from that in benign hyperplastic lymph nodes. This interleukin production may play a role in the development of follicular hyperplasia in myasthenic thymuses, a phenomenon which is associated with the in situ production of autoantibodies. PMID- 1903355 TI - The epidemiology of Neisseria gonorrhoeae isolates in Dakar, Senegal 1982-1986: antimicrobial resistance, auxotypes and plasmid profiles. AB - A total of 460 Neisseria gonorrhoeae isolates from patients seen at three clinics in Dakar, Senegal, 1982-1986, have been investigated. In this period a significant change in antimicrobial susceptibility was observed: the percentage of strains susceptible to penicillin (MIC less than or equal to 0.08 micrograms/ml) fell from 61 to 18 (p less than 0.0001) and the percentage of resistant strains (MIC greater than or equal to 1.2 micrograms/ml) increased from 18 to 46. Among penicillin-resistant strains the proportion of penicillinase producing strains (PPNG) was fairly constant (range 35-55%). The determination of susceptibility to anti-microbial agents performed locally allowed detection of approximately all PPNG strains whereas the increase in the occurrence of strains with chromosomally determined resistance was not revealed. The study comprised 70 PPNG strains of which 19% (13/70) carried the 7.4 kb Asian plasmid and 81% (57/70) the 5.3 kb African plasmid. None of these strains possessed the 38 kb conjugative plasmid, whereas it was found in 4.5% of the 376 non-PPNG strains available for plasmid analysis; 92% (410/446) of all strains had the small 4.2 kb plasmid and 5.4% (24/446) did not contain any plasmid. Overall, auxotype zero and proline-requiring strains were predominant, accounting for 53% (244/460) and 28% (131/460), respectively. In general, PPNG strains carrying the 5.3 kb plasmid were auxotype zero (49/57 = 86%) and those carrying the 7.4 kb plasmid were proline-requiring (9/13 = 69%). PMID- 1903356 TI - Organization and nucleotide sequences of the human tyrosinase gene and a truncated tyrosinase-related segment. AB - We have isolated and sequenced the gene encoding human tyrosinase, the key enzyme in pigment biosynthesis. The human tyrosinase gene contains five exons and spans more than 50 kb of DNA on chromosome segment 11q14----q21. We have also isolated a second segment in the human genome that is closely related to tyrosinase. The tyrosinase-related segment, located on 11p11.2----cen, contains only exons 4 and 5 plus adjacent noncoding regions. This segment is present in all human ethnic groups analyzed, and the noncoding nucleotide sequences shared by the 11q tyrosinase gene and the 11p tyrosinase-related segment differ by only 2.6%. This suggests that this segment of the tyrosinase gene was duplicated approximately 24 million years ago. PMID- 1903357 TI - cDNA sequence and genomic structure of EV12B, a gene lying within an intron of the neurofibromatosis type 1 gene. AB - The gene responsible for neurofibromatosis type 1 (NF1), one of the more common inherited human disorders, was identified recently, and segments of it were cloned. Two translocation breakpoints that interrupt the NF1 gene in NF1 patients flank a 60-kb segment of DNA that contains the EV12A locus (previously reported as the EV12 locus), the human homolog of a mouse gene, Evi-2A, implicated in retrovirus-induced murine myeloid tumors. EVI2A lies within an intron of the NF1 gene and is transcribed from telomere toward centromere, opposite to the direction of transcription of the NF1 gene. Here we describe a second locus, EVI2B, also located between the two NF1 translocation breakpoints. Full-length cDNAs from the EV12B locus detect a 2.1-kb transcript in bone marrow, peripheral blood mononuclear cells, and fibroblasts. Sequencing studies predict an EV12B protein of 448 amino acids that is proline-rich and contains an N-terminal signal peptide, an extracellular domain with four potential glycosylation sites, a single hydrophobic transmembrane domain, and a cytoplasmic hydrophilic domain. At the level of genomic DNA the EV12B locus lies within the same intron of the NF1 gene as EV12A and contains a 57-bp 5' exon that is noncoding, an 8-kb intron, and a 2078-bp 3' exon that includes the entire open reading frame. EV12B is transcribed in the same direction as EV12A; its 5' exon lies only 4 kb downstream from the 3' exon of the EV12A locus. In the mouse the 5' exon of the homologous gene, Evi-2B, lies approximately 2.8 kb from the 3' end of Evi-2A, in the midst of a cluster of viral integration sites identified in retrovirus-induced myeloid tumors; thus, Evi-2B may function as an oncogene in these tumors. PMID- 1903358 TI - The human pre-B-specific lambda-like cluster is located in the 22q11.2-22q12.3 region, distal to the IgC lambda locus. AB - The chromosomal location of the lambda-like gene cluster, a gene family selectively expressed in human pre-B cells, was analyzed by in situ hybridization with a probe specific for the lambda-like genes. This cluster mapped in the q11.2 q12.3 region of chromosome 22. The use of Burkitt lymphoma and myelogenous leukemia cell lines with translocations in the 22q11 region led to a refinement in the location according to the following order: cen----BCRL2, VpreB, IgV lambda 1----BCRL4, IgV lambda----IgC lambda----BCR----BCRL3, lambda-like----tel. Unlike those of the mouse system, the pre-B-specific genes VpreB and lambda-like do not belong to the same transcriptional unit. PMID- 1903359 TI - Extracorporeal membrane oxygenation. Consensus development statement. Australian Association of Paediatric Teaching Centres, in conjunction with the National Health & Medical Research Council and Royal Children's Hospital, Melbourne. PMID- 1903361 TI - Operational evaluation of the efficacy of vaccines by the case control method. AB - To maintain high efficacy and cost-effectiveness of health interventions, such as immunization programs and health information, systematic and careful evaluation is necessary. This is particularly relevant when health resources are scarce, as in most developing countries. Whereas vaccines used in immunization programs are generally evaluated for efficacy and safety prior to their application in routine health service, very little attention is paid to continuous or operational evaluation. Because of practical reasons (cost, time, feasibility, etc.) or ethical reasons (randomization), the most reliable method for evaluation, the classical RCT, cannot be applied for the operational evaluation of vaccine efficacy, and alternative methods such as the case control method are needed. This method is relatively cheap, quicker, poses fewer ethical problems, and can also provide continuous evaluation. PMID- 1903360 TI - On the (near) equivalence of cost-effectiveness and cost-benefit analyses. AB - Many people believe that cost-effectiveness (CE) and cost-benefit (CB) analyses require different assumptions. However, when CE analysis supports decisions to use medical resources, it makes the same assumptions that CB analysis requires. They are mathematically equivalent. Differences between CE and CB hinge more on reporting style than on fundamental assumptions. PMID- 1903362 TI - [Therapy of osteoporosis using the ADFR schedule (especially with parathyroid hormone and etidronate)]. PMID- 1903363 TI - Cytokine-induced modulation of cellular proteins in retinoblastoma. Analysis by flow cytometry. AB - Cytokines are a group of specialized, hormone-like proteins that can exert profound influences on cellular development and on a variety of cellular functions. Retinoblastoma cells are an important model for exploring human malignancy and differentiation. These multipotent embryonic cells are capable of differentiating into neuronal, glial-like and retinal pigment epithelium (RPE) like elements. This report shows that flow cytometric analysis can be used to measure the expression of both cytoplasmic and cell surface proteins in retinoblastoma cells. The authors used this technique to monitor changes in the expression of selected cellular proteins after exposure to specific cytokines and found that MHC class I molecules were augmented by interferon-alpha (IFN-alpha) and interferon-gamma (IFN-gamma), but not by tumor necrosis factor (TNF). However, the MHC class II molecules were augmented by IFN-gamma but not by IFN alpha or TNF. The neuronal markers, IRBP and PR-6, the glial-like marker, GFAP, and the RPE cell markers, RPE-9 and RPE-15, were not altered by any of the cytokines tested. Furthermore, IFN-gamma induced a striking enhancement of the expression of the photoreceptor cell protein, S-antigen. In contrast, IFN-alpha and TNF did not affect the expression of S-antigen. These studies show that the cytokine, IFN-gamma, can enhance a distinct cellular protein associated with cells committed to a specific cell lineage. PMID- 1903364 TI - Primary culture of human retinal glia. AB - Glial cells of the human retina participate in various pathologic processes characterized by cell migration, proliferation, and extracellular matrix production. To study these events in vitro, a procedure was developed to obtain primary cultures of human retinal glial cells. The cultures resulting from the processing of 130 globes contained cells with variable morphology including bipolar and multipolar or stellate cells. Most cells in the primary culture were labeled with antisera to the glial fibrillary acidic protein. The cultures were also examined with antibodies directed against factor VIII-related antigen and muscle-specific actin to determine the presence of endothelial cells and pericytes. A variable contamination of cells staining for the latter was found in these cultures (usually less than 10%). Together, these data indicated that the primary cultures arose principally from glial cells of the human retina but did not precisely identify the cell of origin. PMID- 1903365 TI - Autoradiographic mapping of the glucose transporter with cytochalasin B in the mammalian eye. AB - The anatomic localization of the glucose transport protein in the eyes of rats, rabbits, baboons, marmosets, and humans with [3H]cytochalasin B using in vitro autoradiography showed high densities of glucose carrier densities. These densities were seen in the ciliary body, especially ciliary processes, iris, retina, and in some species, the trabecular meshwork and lens. In the lens, specific [3H]cytochalasin B-binding sites were mainly concentrated in the lens nucleus. Lower concentrations were found in the cortex. During aging, glucose transporter concentration increases up to the age of 8 yr in the marmoset lens nucleus, but decreases in the cortex and retina. Moderate amounts of carrier are located in the corneal endothelium and epithelium. The enrichment of glucose carrier protein in the trabecular meshwork suggests a high metabolic activity and a possible relationship in the regulation of intraocular pressure. PMID- 1903366 TI - Progression of sugar cataract in the dog. AB - Young beagle dogs were fed a 30% galactose diet, with or without the aldose reductase inhibitors sorbinil or M79175. Cataract formation was monitored by indirect ophthalmoscope and hand-held slit-lamp microscopy and documented by retroillumination photography. In these dogs, the first sign of cataract development was an accentuation of the anterior and posterior lens sutures (1 month after feeding), then the appearance of cortical vacuoles (3 months after feeding), and finally, the formation of predominantly equatorial cortical opacities toward the posterior cortices (4-6 months after feeding). After long term galactose feeding, a progressive, irregular, clear zone formed at the cortical equatorial regions. Light microscopic examination of these lenses shows that the cataracts are osmotic, many of the lens fibers appear to be swollen or ruptured, and vacuoles are seen near the bow region. Moreover, these histologic changes were reduced in a dose-dependent manner in galactose-fed dogs concomitantly treated with the aldose reductase inhibitors sorbinil or M79175. The osmotic nature of these cataracts and the observation that their formation can be reduced in a dose-dependent manner by aldose reductase inhibitors are consistent with the concept that the aldose-reductase catalyzed formation of polar sugar alcohols (polyols) initiates sugar cataract formation in the dog. PMID- 1903367 TI - Estimation of glomerular filtration rate from low-dose injection of iohexol and a single blood sample. AB - Clearance of a small dose of iohexol (7 g I) was compared with the glomerular filtration rate (GFR) marker 51Cr EDTA in 11 healthy volunteers. The two tracers were injected simultaneously. The plasma concentration of iohexol was measured with x-ray fluorescence technique. Glomerular filtration rate was determined using blood samples drawn three and four hours after injection. An excellent correlation (0.92 less than r less than 0.97) between iohexol clearance and 51Cr EDTA clearance was found. Glomerular filtration rate can be reliably determined with a low dose of iohexol and a single blood sample obtained three hours after the injection in persons with normal serum creatinine. This new method is a good alternative to the methods using radiopharmaceuticals; it causes no radioactive burden to the patients, increases patient comfort, reduces costs, and requires no special license. PMID- 1903368 TI - Formation rate of nonexchangeable organically bound tritium from tritiated soil water. AB - The role of soil microorganisms in the formation of nonexchangeable organically bound tritium (OBT) from tritiated water (HTO) is investigated. Incubation experiments were conducted with five different soils. They were found to build up OBT at a rate of 0.03-0.05% per week. Addition of a substrate stimulated the formation of OBT up to 0.35% per week. Considering a loss of HTO from the soil by remission, only a negligible fraction of tritium is introduced into the terrestrial food chain. PMID- 1903369 TI - In vitro study of simultaneous infusion of incompatible drugs in multilumen catheters. AB - Multilumen catheters are commonly used to simultaneously administer incompatible drugs to critically ill patients. Though there are no known documented reports that this practice has been responsible for harmful events in patients, likewise there are no published data to verify the safety and efficacy of this practice. This study utilized an in vitro model flow system to examine the physicochemical phenomena that occur when two incompatible drugs (phenytoin and total parenteral nutrition) are simultaneously administered through multilumen catheters. Flow conditions and drug infusions in the venous model were designed to mimic the in vivo clinical situation to evaluate two central venous catheter types, a double- and a triple-lumen catheter. Video recordings were made of drug interactions, and assays of phenytoin concentration were performed on samples of the circulating fluid. White clouds of phenytoin precipitation were observed near the tip of the double-lumen catheter but not the triple-lumen catheter. Infusion through the double-lumen catheter resulted in an average of 6% loss of phenytoin to precipitate, which, on microscopic examination, appeared as spindle-shaped crystals 25 to 50 microns in length and 5 to 10 microns wide. In some cases, millimeter-size fragments of phenytoin precipitate were seen to dislodge from the tip of the double-lumen catheter. The adjacent orifices at the tip of the end hole of the double-lumen catheter appeared to permit interaction of the two effusing streams of the incompatible drugs, whereas the staggered orifices of the triple-lumen catheter reduce this interaction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1903370 TI - Effectiveness of a critical care nursing course: preparing students for practice in critical care. AB - Experiences in critical care in an undergraduate program provide an opportunity for students to develop beginning knowledge and skills for practice in this setting, gain exposure to the role of the nurse in critical care, and acquire competencies essential for care of any acutely ill patient regardless of health problem and setting. The purposes of this study were to (1) examine the acquisition of basic critical care nursing knowledge after completion of an undergraduate course in critical care, (2) compare the differences in learning between students who completed only the theory component of the course and those who completed both theory and clinical practice in critical care, (3) examine learner perceptions toward critical care nursing, and (4) examine the impact of the course on selection by new graduates of critical care as their practice specialty. A quasi-experimental pretest-posttest design was used with two experimental groups: lecture only and lecture and clinical practice, and a randomized control group. Subjects were 85 senior nursing students in a baccalaureate program in a large metropolitan area in the Midwest. Data were collected by using a demographic data sheet, the Basic Knowledge Assessment Tool (BKAT), the Perceptions of Critical Care Nursing Questionnaire (PCCNQ), and follow-up interviews of graduates who completed the course. Both experimental groups demonstrated a statistically significant increase in learning from pretest and posttest, as measured by the BKAT. There were no significant differences in BKAT scores between the lecture and lecture-clinical practice groups. Mean scores on the BKAT at posttest for the experimental groups, who participated in the course, were significantly higher than the control.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1903371 TI - Numerical scoring of treatment plans. AB - This is a report on numerical scoring techniques developed for the evaluation of treatment plans as part of a four-institution study of the role of 3-D planning in high energy external beam photon therapy. A formal evaluation process was developed in which plans were assessed by a clinician who displayed dose distributions in transverse, sagittal, coronal, and arbitrary oblique planes, viewed dose-volume histograms which summarized dose distributions to target volumes and the normal tissues of interest, and reviewed dose statistics which characterized the volume dose distribution for each plan. In addition, tumor control probabilities were calculated for each biological target volume and normal tissue complication probabilities were calculated for each normal tissue defined in the agreed-upon protocols. To score a plan, the physician assigned a score for each normal tissue to reflect possible complications; for each target volume two separate scores were assigned, one representing the adequacy of tumor coverage, the second the likelihood of a complication. After scoring each target and normal tissue individually, two summary scores were given, one for target coverage, the second reflecting the impact on all normal tissues. Finally, each plan was given an overall rating (which could include a downgrading of the plan if the treatment was judged to be overly complex). PMID- 1903372 TI - The role of uncertainty analysis in treatment planning. AB - The role of uncertainty analysis in 3-D treatment planning systems was addressed by four institutions which contracted with NCI to evaluate high energy photon external beam treatment planning. Treatment plans were developed at eight disease sites and the effects of uncertainties assessed in a number of experiments. Uncertainties which are patient-site specific included variations in the delineation of target volumes and normal tissues and the effects of positional uncertainties due to physiological motion and setup nonreproducibility. These were found to have a potentially major impact on the doses to the target volumes and to critical normal tissues which could result in significantly altered probabilities of tumor control and normal tissue complications. Other uncertainties, such as the conversion of CT data to electron densities, heterogeneities and dose calculation algorithms' weaknesses, are related to physical processes. The latter was noted to have the greatest potential contribution to uncertainty in some sites. A third category of uncertainty related to the treatment machine, the consequences of compensator misregistration, are exclusive to the site and the treatment portal. Because conventional treatment planning systems have not incorporated uncertainty analysis, tools and techniques had to be devised for this work; further development in this area is needed. Many of the analyses could not have been done without full 3-D capabilities of the planning systems, and it can be anticipated that the availability of uncertainty analysis in these systems which allow nontraditional beam arrangements will be of great value. PMID- 1903373 TI - Development of the distal end and Tomes' processes of ameloblasts observed by freeze-fracture and ultrathin section electron microscopy. AB - A freeze-fracture examination of distal portions of differentiating and secretory ameloblasts was carried out using upper molar tooth germs from one to four days old rats. Ultrathin sections were prepared for comparison. Freeze-fracture provides a unique opportunity to observe plasma membrane events in distal portions of ameloblasts during differentiation and development. Our results suggest that the distal plasma membrane and Tomes' processes of differentiating and secretory ameloblasts are highly active in endocytosis. In differentiating ameloblasts, endocytic activity is likely to be associated with removal of the basal lamina. During matrix secretion and maturation, ameloblasts are probably removing material from the maturing matrix; in particular amelogenins and water. The present study provides morphological evidence that an endosomal system is present in differentiating and secretory ameloblasts during periods of endocytic activity. This would provide a system whereby ligands, fluid components, membrane receptors and plasma membrane, which enter the cells during endocytosis, may be separated from each other and sorted out for despatch to different destinations. PMID- 1903375 TI - Purification and properties of a chromosomal beta-lactamase from Klebsiella oxytoca. AB - A beta-lactamase was purified from Klebsiella oxytoca strain GN10650. The enzyme was chromosomally-mediated and gave a single protein band on polyacrylamide gel electrophoresis. Its pI was 5.34 and its MW was approximately 27,000. The optimal pH and temperature were about 7.0 and 50 degrees C, respectively. The specific activity of the enzyme was 1,207 units per mg of protein for hydrolysis of penicillins and cephalosporins, including cefuroxime, cefotaxime, and aztreonam. The enzyme activity was inhibited by p-chloromercuribenzoate, iodine, ferrous ion, and by clavulanic acid. Rabbit antibodies raised against the purified K. oxytoca enzyme showed no cross-reactivity in neutralization tests with beta lactamases produced by other species of Gram-negative bacteria. PMID- 1903374 TI - A study of the capacity of various eicosanoids to stimulate skeletal muscle formation in chicken embryos. AB - Inhibitors of prostaglandin synthetase decrease the number of fibres in chicken embryo skeletal muscles (McLennan, 1987a), raising the possibility that muscle formation may be capable of being stimulated by an eicosanoid (prostaglandins, leukotrienes and related substances). This hypothesis has been examined by determining the effect of various prostaglandins and related drugs on fibre formation in vivo. Of the eicosanoids tested, only the E and I series PGs altered muscle formation. PGE2 decreased the number of fibres whereas 16,16-dimethylPGE2 increased fibre formation. Tranylcypromine (TR), an inhibitor of PGI2 formation, decreased fibre formation and PGI2 reversed the action of TR. Fibre numbers were unaffected by A, D and F alpha series prostaglandins, a thromboxane agonist and a lipoxygenase inhibitor. The mechanism by which E and I series prostaglandins exert their effect on chicken embryos remains to be determined but the possibility that a PGE antagonist or PGI2 antagonist may be used to stimulate muscle formation is worthy of further examination. PMID- 1903376 TI - Studies on WF-3681, a novel aldose reductase inhibitor. IV. Effect of FR-62765, a derivative of WF-3681, on the diabetic neuropathy in rats. AB - Pharmacokinetic properties of WF-3681 and FR-62765 in rats were examined. FR 62765 showed higher peak concentrations in the plasma and higher concentrations in the sciatic nerve than WF-3681 when each compound was administered orally to rats. We therefore evaluated FR-62765 in rats with diabetic neuropathy. As a result, FR-62765 at 32 mg/kg/day administered for 3 weeks to streptozotocin induced diabetic rats significantly prevented the accumulation of sorbitol in the sciatic nerve and the reduction of motor nerve conduction velocity in the tail. From these results it was concluded that the aldose reductase inhibitor FR-62765 might be a useful drug for diabetic neuropathy. PMID- 1903378 TI - Enantiospecific synthesis and biological evaluation of 1,6-epi-cyclophellitol. PMID- 1903377 TI - New triene-beta-lactone antibiotics, triedimycins A and B. PMID- 1903379 TI - Maximal aerobic exercise in pregnant women: heart rate, O2 consumption, CO2 production, and ventilation. AB - This study was to determine whether pregnancy affects maximal aerobic power. We measured heart rate, O2 uptake (VO2), CO2 production (VCO2), and ventilation at rest and during bicycle (BE) and treadmill exercise (TE) tests with rapidly increasing exercise intensities at 16, 25, and 35 wk gestation and 7 wk after delivery. Maximal heart rate was slightly lower throughout pregnancy compared with the nonpregnant state during both BE [174 +/- 2 vs. 178 +/- 2 (SE) beats/min] and TE (178 +/- 2 vs. 183 +/- 2 beats/min). Maximal VO2 was unaffected by pregnancy during BE and TE (2.20 +/- 0.08, 2.16 +/- 0.08, 2.15 +/- 0.08, and 2.19 +/- 0.08 l/min for BE and 2.45 +/- 0.08, 2.38 +/- 0.09, 2.33 +/- 0.09, and 2.39 +/- 0.08 l/min for TE at 16, 25, and 35 wk gestation and 7 wk postpartum, respectively). As a result of increased VO2 at rest, the amount of O2 available for exercise (exercise minus rest) tended to decrease with advancing gestation, reaching statistical significance only during TE at 35 wk gestation (1.99 +/- 0.08 l/min vs. 2.10 +/- 0.08 l/min postpartum). Power showed a positive linear correlation with O2 availability during BE as well as TE, and the relationship was unaffected by pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1903380 TI - In vitro perfused-superfused cat carotid body for physiological and pharmacological studies. AB - An in vitro perfused carotid body preparation was developed to study its chemosensory responses to physiological and pharmacological stimuli. The carotid bifurcation with the carotid body was vascularly isolated and excised from pentobarbital sodium-anesthetized cats. The CB was perfused in a chamber by gravity (80 Torr) with modified Tyrode's solution (N-2-hydroxyethylpiperazine-N' 2-ethanesulfonic acid-NaOH at pH 7.40) equilibrated at a given Po2 and superfused with the same medium at (Po2 of 20 Torr). The temperature was maintained at 35.5 +/- 0.5 degrees C. The frequency of chemosensory discharges (CD) was recorded from the whole carotid sinus nerve (n = 24), and the responses were tested by repeated interruptions of perfusate flow (SF), perfusion with hypoxic medium, and injections of nicotine and cyanide (0.1 nmol to 1 mumol) and hypercapnic medium. During hyperoxic perfusion, SF resulted in a sigmoidal increase in CD, reaching a maximum that was 23.6 +/- 4.4-fold greater than the basal activity. Restoration of flow returned CD promptly to basal values. After normoxic perfusion, SF led to a similar maximal activity more rapidly, but the duration was shorter. Reduction of the perfusate PO2 (Po2 from 450 Torr to 150, 30, and less than 10 Torr) caused a nonlinear increase in CD. CO2 stimuli (PCo2 38-110 Torr) resulted in a linear increase in CD. Nicotine or cyanide increased CD in a dose-dependent manner. The preparation retained its initial responsiveness for 2-3 h, making extensive experimental studies feasible.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1903381 TI - Culture requirements for optimal expression of 1 alpha,25-dihydroxyvitamin D3 enhanced thyrotropin secretion. AB - An effect of the hormone, 1 alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3] on hormone secretion by normal rat pituitary cells was investigated in vitro. Based on previous findings using GH4C1 cells, dispersed anterior pituitary cell cultures were prepared and maintained in serum-free conditions for up to 6 d. Under these circumstances, there was no effect of 1,25(OH)2D3 to alter medium or cell associated levels of thyrotropin (TSH), prolactin (PRL), or growth hormone (GH). Cultures maintained under these conditions had lower medium and cell-associated hormone levels and lesser responses to agonists than cultures maintained in serum supplemented medium. In the presence of 10% charcoal-treated fetal bovine serum, treatment with 10(-8) M 1,25(OH)2D3 for 24 h selectively increased TRH (10(-10) to 10(-7) M)-induced TSH secretion (P less than 0.001), with maximal enhancement observed at 10(-9) M TSH-releasing hormone (TRH). Enhancement of TSH secretion by 1,25(OH)2D3 was detected after 15 min exposure to TRH. There was no effect on agonist-induced PRL or GH secretion or on cell-associated hormone levels. The effect was evident after 24 h treatment with 1,25(OH)2D3, and decreased thereafter. Several other steroid hormones had no effect on 10(-9) M TRH-induced TSH secretion. These data contrast with the effect of 1,25(OH)2D3 in GH cells. They suggest that 1,25(OH)2D3 may act selectively in the normal pituitary to modulate TSH secretion. PMID- 1903382 TI - Pachytene spermatocyte protein(s) stimulate Sertoli cells grown in bicameral chambers: dose-dependent secretion of ceruloplasmin, sulfated glycoprotein-1, sulfated glycoprotein-2, and transferrin. AB - Interactions between pachytene spermatocytes and Sertoli cells were investigated using the bicameral culture chamber system. Pachytene spermatocytes were isolated from adult rats with a purity in excess of 90% by centrifugal elutriation. The pachytene spermatocytes were cultured in a defined media and pachytene spermatocyte protein prepared from the conditioned media by dialysis and lyophilization. This pachytene spermatocyte protein was reconstituted at various concentrations and incubated with confluent epithelial sheets of immature Sertoli cells cultured in bicameral chambers. Pachytene spermatocyte protein stimulated secretion of total [35S]methionine-labeled protein from Sertoli cells in a dose dependent manner predominantly in an apical direction. This stimulatory effect of pachytene spermatocyte protein was domain specific from the apical surface of Sertoli cells, and seemed specific for secretion because total intracellular protein did not increase under the influence of pachytene spermatocyte protein. Pachytene spermatocyte protein and follicle-stimulating hormone additively stimulated Sertoli cell secretion. The physicochemical characteristics of the stimulatory pachytene spermatocyte protein are indicative of heat stability, whereas the stimulatory pachytene spermatocyte protein exhibit acid, dithiothreitol and trypsin sensitivity, and partial urea sensitivity. Furthermore, Sertoli cell secretion of ceruloplasmin, sulfated glycoprotein-1, sulfated glycoprotein-2, and transferrin in response to various concentrations of pachytene spermatocyte protein were determined by immunoprecipitate of these [35S]methionine-labeled proteins with polyclonal antibodies. Maximal stimulation of ceruloplasmin and sulfated glycoprotein-1 secretion from Sertoli cells was observed at a dose of 50 micrograms/ml pachytene spermatocyte protein, whereas maximal stimulation of sulfated glycoprotein-2 and transferrin secretion from Sertoli cells was observed at a dose of 100 micrograms/ml of pachytene spermatocyte protein. These results suggest that pachytene spermatocytes modulate Sertoli cell secretory function of at least four proteins in the regulation of spermatogenesis. PMID- 1903383 TI - Evaluation of the probability of spontaneous transfer of drug resistance between cells in culture. AB - Coculture of two different cell lines in monolayer or spheroids was used to investigate the spontaneous transfer of dominant genes determining drug resistance. MGH-U1 human bladder cancer cells (ouabain-sensitive, mitomycin C resistant) were cocultured with UV-20 cells (a subline of Chinese hamster ovary cells which is ouabain-resistant and mitomycin C-sensitive). We investigated the possible transfer of mitomycin-C resistance from human to rodent cells by selection in both ouabain and mitomycin C. Regardless of coculture conditions, the frequency of surviving cells was at a similar level to that expected from studies of cell survival when cells were cultured alone. We found no evidence of spontaneous transfer of drug resistance between the two cell lines. PMID- 1903384 TI - Nitrogenases. PMID- 1903385 TI - Pyruvate is a by-product of catalysis by ribulosebisphosphate carboxylase/oxygenase. AB - Pyruvate is a minor product of the reaction catalyzed by ribulosebisphosphate carboxylase/oxygenase from spinach leaves. Labeled pyruvate was detected, in addition to the major labeled product, 3-phosphoglycerate, when 14CO2 was the substrate. Pyruvate production was also measured spectrophotometrically in the presence of lactate dehydrogenase and NADH. The Km for CO2 of the pyruvate producing activity was 12.5 microM, similar to the CO2 affinity of the 3 phosphoglycerate-producing activity. No pyruvate was detected by the coupled assay when ribulose 1,5-bisphosphate was replaced by 3-phosphoglycerate or when the carboxylase was inhibited by the reaction-intermediate analog, 2' carboxyarabinitol 1,5-bisphosphate. Therefore, pyruvate was not being produced from 3-phosphoglycerate by contaminant enzymes. The ratio of pyruvate produced to ribulose bisphosphate consumed at 25 degrees C was 0.7%, and this ratio was not altered by varying pH or CO2 concentration or by substituting Mn2+ for Mg2+ as the catalytically essential metal. The ratio increased with increasing temperature. Ribulose-bisphosphate carboxylases from the cyanobacterium Synechococcus PCC 6301 and the bacterium Rhodospirillum rubrum also catalyzed pyruvate formation and to the same extent as the spinach enzyme. When the reaction was carried out in 2H2O, the spinach carboxylase increased the proportion of its product partitioned to pyruvate to 2.2%. These observations provide evidence that the C-2 carbanion form of 3-phosphoglycerate is an intermediate in the catalytic sequence of ribulose-bisphosphate carboxylase. Pyruvate is formed by beta elimination of a phosphate ion from a small portion of this intermediate. PMID- 1903386 TI - The K+ conductance of the inner mitochondrial membrane. A study of the inducible uniport for monovalent cations. AB - Addition of A23187 plus EDTA to rat liver mitochondria induces a common uniport pathway for monovalent cations. In this study, we have carried out a detailed characterization of the flow/force relationship for K+ transport along this pathway under steady state conditions. In the presence of EDTA, the K+ conductance is a linear function of external K+ in the range 0-20 mM K+, with a slope of 0.15 nmol of K+ x mg of protein-1 x min-1 x mV-1. The K+ conductance is inhibited by Mg2+ in the range 10(-9)-10(-6) M, while K+ flux is stimulated by the sulfhydryl group reagent mersalyl. Uniport activity can be detected in native mitochondria. These findings are compatible with the notion that electrophoretic K+ flux across the inner membrane takes place via a regulated K+ uniport with the potential of transporting K+ at rates in excess of 600 nmol x mg of protein-1 x min-1. PMID- 1903387 TI - Structural and functional roles of highly conserved serines in human lipoprotein lipase. Evidence that serine 132 is essential for enzyme catalysis. AB - The structure of human lipoprotein lipase was recently deduced from its cDNA sequence. It contains 8 serine residues (residues 45, 132, 143, 172, 193, 244, 251, and 363) that are absolutely conserved in both lipoprotein lipase and hepatic lipase across all species studied. The high homology between lipoprotein lipase, hepatic lipase, and pancreatic lipase suggests that the catalytic functions of these enzymes share a common mechanism and that one of the 8 conserved serines in human lipoprotein lipase must play a catalytic role as does serine 152 in the case of pancreatic lipase (Winkler, F. K., D'Arcy, A., and Hunziker, W. Nature 343, 771-774). We expressed wild-type and site-specific mutants of human lipoprotein lipase in COS cells in vitro. We produced two to four substitution mutants involving each of the 8 serines and assayed a total of 22 mutants for both enzyme activity and the amount of immunoreactive enzyme mass produced. Immunoreactive lipase was detected in all cases. With the exception of Ser132, for each of the 8 serine mutants we studied, at least one of several mutants at each position showed detectable enzyme activity. All three substitution mutants at Ser132, Ser----Thr, Ser----Ala, and Ser----Asp, were totally inactive. Ser132 occurs in the consensus sequence Gly-Xaa-Ser-Xaa-Gly present in all serine proteinases and in human pancreatic lipase. The x-ray crystallography structure of human pancreatic lipase suggests that the analogous serine residue in human pancreatic lipase, Ser152, is the nucleophilic residue essential for catalysis. Our biochemical data strongly support the conclusion that Ser132 in human lipoprotein lipase is the crucial residue required for enzyme catalysis. The observed specific activities of the variants involving the other seven highly conserved serines in human lipoprotein lipase are consistent with the interpretation that this enzyme has a three-dimensional structure very similar to that of human pancreatic lipase. PMID- 1903388 TI - Phycoerythrins of marine unicellular cyanobacteria. I. Bilin types and locations and energy transfer pathways in Synechococcus spp. phycoerythrins. AB - Marine Synechococcus strains WH8103, WH8020, and WH7803 each possess two different phycoerythrins, PE(II) and PE(I), in a weight ratio of 2-4:1. PE(II) and PE(I) differ in amino acid sequence and in bilin composition and content. Studies with strain WH7803 indicated that both PE(II) and PE(I) were present in the same phycobilisome rod substructures and that energy absorbed by PE(II) was transferred to PE(I). Strain WH8103 and WH8020 PE(I)s carried five bilin chromophores thioether-linked to cysteine residues in sequences homologous to those previously characterized in C-, B-, and R-PEs. In contrast, six bilins were attached to strain WH8103 and WH8020 PE(II)s. Five of these were at positions homologous to bilin attachment sites in other phycoerythrins. The additional bilin attachment site was on the alpha subunit. The locations and bilin types in these PE(s) and in the marine Synechocystis strain WH8501 PE(I) (Swanson, R. V., Ong, L. J., Wilbanks, S. M., and Glazer, A. N. (1991) J. Biol. Chem. 266, 9528 9534) are: (table; see text) Since phycourobilin (PUB) (lambda max approximately 495 nm) transfers energy to phycoerythrobilin (PEB) (lambda max approximately 550 nm), inspection of these data shows that the invariant PEB group at beta-82 is the terminal energy acceptor in phycoerythrins. The adaptations to blue-green light, high PUB content and the presence of an additional bilin on the alpha subunit, increase the efficiency of light absorption by PE(II)s at approximately 500 nm. PMID- 1903389 TI - Phycoerythrins of marine unicellular cyanobacteria. II. Characterization of phycobiliproteins with unusually high phycourobilin content. AB - A survey of marine unicellular cyanobacterial strains for phycobiliproteins with high phycourobilin (PUB) content led to a detailed investigation of Synechocystis sp. WH8501. The phycobiliproteins of this strain were purified and characterized with respect to their bilin composition and attachment sites. Amino-terminal sequences were determined for the alpha and beta subunits of the phycocyanin and the major and minor phycoerythrins. The amino acid sequences around the attachment sites of all bilin prosthetic groups of the phycocyanin and of the minor phycoerythrin were also determined. The phycocyanin from this strain carries a single PUB on the alpha subunit and two phycocyanobilins on the beta subunit. It is the only phycocyanin known to carry a PUB chromophore. The native protein, isolated in the (alpha beta)2 aggregation state, displays absorption maxima at 490 and 592 nm. Excitation at 470 nm, absorbed almost exclusively by PUB, leads to emission at 644 nm from phycocyanobilin. The major and minor phycoerythrins from strain WH8501 each carry five bilins per alpha beta unit, four PUBs and one phycoerythrobilin. Spectroscopic properties determine that the PUB groups function as energy donors to the sole phycoerythrobilin. Analysis of the bilin peptides unambiguously identifies the phycoerythrobilin at position beta-82 (residue numbering assigned by homology with B-phycoerythrin; Sidler, W., Kumpf, B., Suter, F., Klotz, A. V., Glazer, A. N., and Zuber, H. (1989) Biol. Chem. Hoppe-Seyler 370, 115-124) as the terminal energy acceptor in phycoerythrins. PMID- 1903390 TI - Phycoerythrins of marine unicellular cyanobacteria. III. Sequence of a class II phycoerythrin. AB - The genes for the alpha and beta subunits of a novel six bilin-bearing (class II) phycoerythrin were cloned from Synechococcus sp. WH8020 and sequenced. The cloned genes (mpeA and mpeB) were detected by homology with the genes for C phycoerythrin from Pseudanabaena sp. PCC7409. The mpe locus occurs once in the genome and is arranged similarly to that of many other phycobiliproteins, with mpeA shortly 3' of mpeB. Sequence comparison suggests that this phycoerythrin (and perhaps all class II phycoerythrins) occupy a branch of the phycoerythrin family separate from five-chromophore per alpha beta (class I) phycoerythrins, C phycoerythrin, and B-phycoerythrin. The position of the sixth chromophore of the class II phycoerythrin of WH8020 was determined by comparison of the amino acid sequence of the chromopeptides (Ong, L. J., and Glazer, A. N. (1991) J. Biol Chem. 266, 9515-9527) with the sequence deduced from the gene. This located the chromophore at residue 75 of the alpha subunit, very close to the alpha-83 chromophore in the primary structure and, presumably, in the three-dimensional structure. PMID- 1903391 TI - Gamma-subunits of G proteins, but not their alpha- or beta-subunits, are polyisoprenylated. Studies on post-translational modifications using in vitro translation with rabbit reticulocyte lysates. AB - Lipid modifications that may be introduced into several subunits of G proteins were explored by in vitro translation of recombinant mRNAs in reticulocyte lysates. In agreement with studies by others, myristic acid was incorporated into alpha i's and alpha o, but not alpha s, beta, or gamma's. In contrast, mevalonate (Mev) was incorporated only into gamma-subunits. Both, the gamma-subunit of transducin (gamma T) and that of other G proteins (gamma G) were modified by the lysates but with different characteristics. Labeled gamma T was unstable and was rapidly proteolyzed. Labeled gamma G was stable. The Mev-derivative in gamma G was sensitive to methyliodide and, after cleavage and chromatographic analysis, comigrated with the C20 polyisoprenol geranylgeraniol. This indicated that gamma G had been geranylgeranylated and that this polyisoprenoid was attached to the protein through a thioether linkage. It is thought that polyisoprenylation is defined by the COOH-terminal sequence Cys-A-A-X, where A is an aliphatic acid and X is any amino acid. Replacement by mutation of the Cys of the COOH-terminal -Cys Ala-Ile-Leu sequence of gamma G with Ser abolished Mev incorporation, suggesting this Cys as the site of attachment of the geranylgeranyl moiety. Yet, Mev incorporation was less than 10% as much into gamma G with the Cys-A-A-X sequence Cys-Ala-Ile-Trp. Consistent with geranylgeranylation, the C15 farnesyl moiety of farnesyl pyrophosphate was not incorporated into gamma G unless the incubations were fortified with Mev. In contrast, the farnesyl moiety was incorporated in an Mev-independent manner into gamma T (COOH terminus: -Cys-Val-Ile-Ser) and c-Ha ras (COOH terminus: -Cys-Val-Leu-Ser) which are both farnesylated rather than geranylgeranylated. Thus, 1) separate enzymes appear to be involved in transferring farnesyl and geranylgeranyl groups to proteins, 2) structural factors other than the CAAX box contribute to the activity of the polyisoprenylating enzymes, and 3) this type of lipidation may be part of a proteolytic signaling system. Polyisoprenylation, which increases hydrophobicity of the derivatized protein, may play a role in anchoring not only ras but also G proteins to membranes. PMID- 1903392 TI - Expression, isolation, and characterization of an active site (serine 528--- alanine) mutant of recombinant bovine prothrombin. AB - An active site mutant bovine prothrombin cDNA (Ser528----Ala) has been constructed, subcloned, and expressed in Chinese hamster ovary cells. The recombinant mutant prothrombin, expressed at the level of 1.5-2.0 micrograms/ml of cell medium, was fully carboxylated (9.9 +/- 0.4 mol of gamma-carboxyglutamic acid/mol of prothrombin). The mutant prothrombin could be activated to thrombin by Taipan snake venom and activated to meizothrombin by ecarin in a manner comparable to native bovine prothrombin or recombinant wild-type bovine prothrombin. The mutant meizothrombin thus formed was stable and did not autolyze. The initial rate of cleavage of mutant prothrombin catalyzed by the full prothrombinase was only 28% of the rate of cleavage of native prothrombin, while recombinant wild-type prothrombin was cleaved at the same rate as the native molecule. The mutant thrombin, obtained from the mutant prothrombin in situ by prothrombinase or Taipan snake venom activation, showed no enzymatic activity toward either fibrinogen or a synthetic chromogenic substrate, D phenylalanyl-L-pipecolyl-L-arginine-p-nitroanilide dihydrochloride (S2238). The mutant thrombin also bound dansylarginine-N-(3-ethyl-1,5-pentanediyl)amide, a specific fluorescent inhibitor of the thrombin active site, with a weaker binding affinity (kd = 5.4 x 10(-8) M) than did native thrombin (kd = 1.7 x 10(-8) M). These results indicate that the mutant recombinant prothrombin described here is a useful tool for the study of meizothrombin or thrombin without the complications arising from the proteolytic activities of these molecules. Study of the activation of this mutant has already revealed a functional link between the site of initial cleavage by the prothrombinase and the conformation at the nascent active site of prothrombin. PMID- 1903393 TI - Structural features of the arabinan component of the lipoarabinomannan of Mycobacterium tuberculosis. AB - The recent availability of pure lipoarabinomannan (LAM) from Mycobacterium spp. has resulted in its implication in host-parasite interaction, which events may be mediated by the presence of a phosphatidylinositol unit at the reducing end of LAM. Herein we address the structure of the antigenic, nonreducing end of the molecule. Through the process of 13C NMR analysis of the whole molecule and gas chromatography/mass spectrometry of alditol acetates derived from the differential per-O-alkylated lipopolysaccharide, the majority of the arabinosyl residues were recognized as furanosides. Second, through analysis of per-O alkylated oligoarabinosyl arabinitol fragments of partially hydrolyzed LAM, it was established that the internal segments of the arabinan component consists of branched 3,5-linked alpha-D-arabinofuranosyl (Araf) units with stretches of linear 5-linked alpha-D-Araf residues attached at both branch positions, whereas the nonreducing terminal segments of LAM consist of either of the two arrangements, beta-D-Araf-(1----2)-alpha-D-Araf-(1----5)- alpha-D-Araf---- or [beta-D-Araf-(1----2)-alpha-D-Araf-(1----]2---- (3 and 5)-alpha-D-Araf----. Since this latter arrangement also characterizes the terminal segments of the peptidoglycan-bound arabinogalactan of Mycobacterium spp., we propose that mycobacteria elaborate unique terminal arabinan motifs in two distinct settings. In the case of the bound arabinogalactan, these motifs provide the nucleus for the esterified mycolic acids, entities which dominate the physicochemical features of mycobacteria and their peculiar pathogenesis. In the case of LAM, these motifs, non-mycolylated, are the dominant B-cell antigens responsible for the majority of the copious antibody response evident in most mycobacterial infections. PMID- 1903395 TI - Characterization of a GTPase-activating protein for the Ras-related Ral protein. AB - We have demonstrated the presence of a GTPase-activating protein (GAP) for the Ras-related Ral A protein in the cytosolic fraction of brain and testis. This protein, designated Ral-GAP, was distinguished from Ras-GAP by its behavior in two chromatography systems and by the fact that the two GAP proteins did not stimulate the GTPase activity of each others target GTP binding proteins. The lack of effect of Ral-GAP on Ras GTPase activity also distinguished it from the product of the neurofibromatosis gene NF-1. Ral-GAP also differed from Rho-GAP and Rap-GAP by virtue of its elution from a gel filtration column with proteins of Mr greater than 10(6). This was likely an overestimate of the protein's molecular mass, however, since it sedimented in sucrose gradients between standard proteins of 150 and 443 kDa. Ral-GAP failed to promote the GTPase activity of mutant Ral proteins containing amino acid substitutions that in Ras lead to GAP-insensitive proteins. PMID- 1903394 TI - Cell surface molecules that bind fibronectin's matrix assembly domain. AB - The assembly of fibronectin into disulfide cross-linked extracellular matrices requires the interaction of mesenchymal cells with two distinct sites on fibronectin, the Arg-Gly-Asp cell adhesive site and an amino-terminal site contained within the first five type I homologous repeats (Quade, B. J., and McDonald, J. A. (1988) J. Biol. Chem. 263, 19602-19609). Proteolytically derived 29-kDa fragments of fibronectin (29kDa) containing these repeats bind to monolayers of cultured fibroblasts and inhibit fibronectin matrix assembly. The cell surface molecules interacting with fibronectin's 29-kDa matrix assembly domain have resisted purification using conventional methods such as affinity chromatography. Accordingly, in order to identify molecules which bind this fragment, 125I-labeled 29kDa was allowed to bind to fibroblast monolayers and chemically cross-linked to the cell surface with bis(sulfosuccinimidyl) suberate. Extraction of the cross-linked cell layer yielded radiolabeled complexes of 56, 150, and 280 kDa. Formation of these cross-linked complexes was specifically inhibited by the addition of excess unlabeled 29kDa but was unaffected by the presence of fibronectin fragments containing other type I repeats outside of the 29kDa matrix assembly domain. The cross-linked complexes were insoluble in nondenaturing detergents but soluble when denatured and reduced, suggesting that 29kDa may be cross-linked to components of the pericellular matrix. Immunoprecipitation of cross-linked cell extracts with a polyclonal antibody to fibronectin that does not recognize the amino terminus demonstrate that the 280 kDa band contains 29kDa cross-linked to fibronectin present on the cell surface. Formation of the 150-kDa complex was inhibited by EDTA, suggesting that divalent cations are required for its formation. Although the molecular mass and divalent cation requirement suggest that the 150-kDa complex may be related to an integrin, this complex was not immunoprecipitated by polyclonal antibodies generated to the alpha 5 beta 1 integrin fibronectin receptor. PMID- 1903396 TI - Partial characterization of a new isoenzyme of carbonic anhydrase isolated from Chlamydomonas reinhardtii. AB - A new isoenzyme of carbonic anhydrase has been isolated and purified from Chlamydomonas reinhardtii. This carbonic anhydrase is composed of two nonidentical subunits with apparent molecular masses of 39 and 4.5 kDa and is located in the periplasmic space. This is the second periplasmic carbonic anhydrase found in C. reinhardtii. Two genes, CAH1 and CAH2, which code for carbonic anhydrase, have been recently described by Fujiwara et al. (Fujiwara, S., Fukuzawa, H., Tachiki, A., and Miyachi, S. (1990) Proc. Natl. Acad, Sci. U.S.A. 87, 9779-9783). The CAH1 gene codes for a periplasmic carbonic anhydrase which is induced under low CO2 conditions and is well characterized. The carbonic anhydrase characterized in this report was isolated from a mutant that is unable to synthesize the CAH1 gene product. Amino acid sequencing demonstrates that this newly isolated carbonic anhydrase is the CAH2 gene product. This is the first report of another functional carbonic anhydrase in C. reinhardtii. PMID- 1903397 TI - Purification of glutamyl-tRNA reductase from Synechocystis sp. PCC 6803. AB - delta-Aminolevulinic acid is the universal precursor for all tetrapyrroles including hemes, chlorophylls, and bilins. In plants, algae, cyanobacteria, and many other bacteria, delta-aminolevulinic acid is synthesized from glutamate in a reaction sequence that requires three enzymes, ATP, NADPH, and tRNA(Glu). The three enzymes have been characterized as glutamyl-tRNA synthetase, glutamyl-tRNA reductase, and glutamate-1-semialdehyde aminotransferase. All three enzymes have been separated and partially characterized from plants and algae. In prokaryotic phototrophs, only the glutamyl-tRNA synthetase and glutamate-1-semialdehyde aminotransferase have been decribed. We report here the purification and some properties of the glutamyl-tRNA reductase from extracts of the unicellular cyanobacterium, Synechocystis sp. PCC 6803. The glutamyl-tRNA reductase has been purified over 370-fold to apparent homogeneity. Its native molecular mass was determined to be 350 kDa by glycerol density gradient centrifugation, and its subunit size was estimated to be 39 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The N-terminal amino acid sequence was determined for 42 residues. Much higher activity occurred with NADPH than with NADH as the reduced pyridine nucleotide substrate. Half-maximal rates occurred at 5 microM NADPH, whereas saturation was not reached even at 10 mM NADH. Purified Synechocystis glutamyl-tRNA reductase was inhibited 50% by 5 microM heme. Activity was unaffected by 10 microM 3-amino-2,3-dihydrobenzoic acid. No flavin, pyridine nucleotide, or other light-absorbing prosthetic group was detected on the purified enzyme. The catalytic turnover number of purified Synechocystis glutamyl tRNA reductase is comparable to those of prokaryotic and plastidic glutamyl-tRNA synthetases. PMID- 1903398 TI - Characterization and regulation of the Pseudomonas aeruginosa algC gene encoding phosphomannomutase. AB - The nucleotide sequence of the Pseudomonas aeruginosa algC gene encoding phosphomannomutase (PMM; EC 5.4.2.8) was determined. The codon usage in algC in the wobble base position was 90.4% G+C, typical of Pseudomonas genes. The predicted amino acid sequence of phosphomannomutase (PMM) showed homology over a stretch of 112 amino acids in the carboxyl terminus with rabbit muscle phosphoglucomutase (PGM), an enzyme that catalyzes a reaction analogous to that catalyzed by PMM. In addition, a specific amino acid sequence within PMM showed homology with the catalytic site of PGM. DNA sequence analysis of a defective algC gene (algC') cloned from a mutant of P. aeruginosa that lacked PMM activity revealed one point mutation (a C to T transition) in the carboxyl terminus of PMM which resulted in an amino acid change from arginine 420 to cysteine 420. The mutation identified in the algC' gene was not within the regions of homology with PGM. The algC promoter showed significant homology with the promoters of two other P. aeruginosa genes involved in alginate synthesis, algD and algR1. Both the algD and algR1 promoters are activated by the product of the algR1 gene in P. aeruginosa. The upstream region of the algC gene contained a sequence identical to the algD upstream sequence that is known to be the binding site for the AlgR1 protein. Expression of algC was reduced 5.7-fold in an algR1 mutant of P. aeruginosa compared to its isogenic parent strain (lacking the algR1 mutation), suggesting that the algR1 gene product activates the transcription of the algC gene. PMID- 1903399 TI - Carboxyl-terminal isoprenylation of ras-related GTP-binding proteins encoded by rac1, rac2, and ralA. AB - Membrane localization of p21ras is dependent upon its posttranslational modification by a 15-carbon farnesyl group. The isoprenoid is linked to a cysteine located within a conserved carboxyl-terminal sequence termed the "CAAX" box (where C is cysteine, A is an aliphatic amino acid, and X is any amino acid). We now show that three GTP-binding proteins encoded by the recently identified rac1, rac2, and ralA genes also undergo isoprenoid modification. cDNAs coding for each protein were transcribed in vitro, and the RNAs were translated in reticulocyte lysates. Incorporation of isoprenoid precursors, [3H]mevalonate or [3H]farnesyl pyrophosphate, indicated that the translation products were modified by isoprenyl groups. A protein recognized by an antibody to rac1 also comigrated with a protein metabolically labeled by a product of [3H] mevalonate in cultured cells. Gel permeation chromatography of radiolabeled hydrocarbons released from the rac1, rac2, and ralA proteins by reaction with Raney nickel catalyst indicated that unlike p21Hras, which was modified by a 15-carbon moiety, the rac and ralA translation products were modified by 20-carbon isoprenyl groups. Site directed mutagenesis established that the isoprenylated cysteines in the rac1, rac2, and ralA proteins were located in the fourth position from the carboxyl terminus. The three-amino acid extension distal to the cysteine was required for this modification. The isoprenylation of rac1 (CSLL), ralA (CCIL), and the site directed mutants rac1 (CRLL) and ralA (CSIL), demonstrates that the amino acid adjacent to the cysteine need not be aliphatic. Therefore, proteins with carboxyl terminal CXXX sequences that depart from the CAAX motif should be considered as potential targets for isoprenoid modification. PMID- 1903400 TI - Functional analyses of promoter elements responsible for the differential expression of the human metallothionein (MT)-IG and MT-IF genes. AB - The sequences responsible for heavy metal-inducible expression are situated within the proximal 437 and 160 base pairs (bp) of MT-IF and MT-IG 5'-flanking sequence, respectively. Only 105 bp of proximal MT-IG 5'-flanking sequence containing a TATA box, two metal responsive elements (MREs), and three GC motifs and 147 bp of proximal MT-IF 5'-flanking sequence containing a TATCA box, four MREs, and two GC motifs were required for heavy metal-inducible expression. However, the proximal 111 bp of MT-IF 5'-flanking sequences (a TATCA box, two MREs, and two GC motifs) was not responsive to heavy metals and competes less efficiently than the 105-bp MT-IG fragment in a competition transfection analysis. The MT-IF promoter fragment containing MREc and MREd is substantially stronger and a more efficient competitor than the MT-IG promoter fragment containing MREc and MREd. Furthermore, the proximal 160 bp of MT-IG 5'-flanking sequence functions as a strong metal-inducible promoter but not as a metal inducible enhancer. Mobility shift analysis of MT-IF and MT-IG promoter subregions suggests a correlation between protein binding to MRE sequences and MT gene expression. These data illustrate that the overall structural and functional organization of the MT-IF and MT-IG promoters are very different and that the molecular mechanisms governing differential expression levels of human MT genes are quite complex. PMID- 1903401 TI - Prediction of cognitive competence in Kenyan children from Toddler nutrition, family characteristics and abilities. AB - This study explored the extent to which cognitive competence in 5-yr old Kenyan children was associated with earlier nutritional factors, family conditions and toddler characteristics. Food intake during the 18th-30th mths and physical stature at 30 mths were associated with cognitive skills at 5 yrs. Measures of family background, abilities of the child as a toddler and current schooling were also associated with cognitive abilities at 5 yrs. These variables influenced development independently, so that later cognitive competence was best predicted by a combination of earlier nutritional, family and toddler characteristics. PMID- 1903402 TI - Kappa light chain predominance in serum and cerebrospinal fluid from human immunodeficiency virus type 1 (HIV-1)-infected patients. AB - We measured kappa/lambda light chain ratios of Ig and IgG in 41 serum and 34 cerebrospinal fluid (CSF) samples from 47 patients at different clinical stages of human immunodeficiency virus type 1 (HIV-1) infection and in serum and CSF samples from control subjects. Both ratios were more elevated in HIV-1 seropositive subjects than controls. The elevation was more evident in samples from asymptomatic seropositive patients (ASP) than those from patients with acquired immunodeficiency syndrome (AIDS). In addition, there was a statistically significant elevation of Ig kappa/lambda ratios in ASP CSF compared to serum. We also delineated the light chain composition of oligoclonal IgG bands (OCB) by isoelectric focusing followed by immunofixation in CSF and serum samples from selected ASP and patients with AIDS who had neurological involvement. Five of six AIDS and all seven ASP samples had IgG OCB exclusively or predominantly of the kappa type. Four IgG OCB of the lambda type and one free lambda chain band were seen in CSF from a pediatric AIDS patient. The presence of an abnormally elevated kappa/lambda ratio correlated with the presence of IgG kappa OCB (p less than 0.02). We conclude that HIV-1 infection is associated with a kappa light chain predominance and with OCB mainly composed of kappa light chains. PMID- 1903403 TI - National Institutes of Health summary of the Consensus Development Conference on Sunlight, Ultraviolet Radiation, and the Skin. Bethesda, Maryland, May 8-10, 1989. Consensus Development Panel. PMID- 1903404 TI - Coronary patency, infarct size and left ventricular function after thrombolytic therapy for acute myocardial infarction: results from the tissue plasminogen activator: Toronto (TPAT) placebo-controlled trial. TPAT Study Group. AB - Infarct size, left ventricular function and infarct-related coronary artery patency were examined in 108 patients who took part in a previously reported placebo-controlled trial of recombinant tissue-type plasminogen activator (rt-PA) in acute myocardial infarction. Coronary angiography was performed 17 +/- 0.8 h after initiation of treatment in 47 patients (group A) or at 10 days in 61 patients (group B). Both groups underwent radionuclide ventriculography 3.8 +/- 0.8 h and again on day 9 after treatment and quantitative thallium scintigraphy on day 8. In group A, the infarct-related artery was patent in 53%; these patients had a smaller global (15.1 +/- 2.5% vs. 25.7 +/- 4.7%, p = 0.029) and regional (14.7 +/- 2.5% vs. 24.1 +/- 4.7%, p = 0.044) fixed thallium defect than did those with an occluded artery. Infarct regional ejection fraction improved by 10.1 +/- 2.1% between early and late studies when the infarct-related artery was patent and by 4.8 +/- 1.4% if it was occluded (p = 0.048); changes in global and noninfarct regional ejection fraction were similar irrespective of perfusion status. Infarct regional ejection fraction and fixed thallium defect were inversely related only when the infarct-related artery was occluded (r = -0.83, p less than 0.0001). In group B, 10 day patency of the infarct-related artery was 67%; there was no difference in patency by treatment assignment or in left ventricular function or infarct size between patients with and without infarct related artery patency. There was no evidence of an effect of rt-PA therapy beyond that expressed through coronary patency alone in either group A or group B. PMID- 1903406 TI - Clinically enhancing nursing practice. Improving feeding skills. AB - 1. The aim of nurses assisting elders with eating is to maintain the resident's existing abilities or recover, as much as possible, lost abilities. 2. The findings of this study indicated that nurses did not understand the importance of sitting while feeding elderly residents. 3. More than one quarter (28%) of the nursing staff surveyed were unable to identify age-related changes that may increase the possibility of choking. PMID- 1903405 TI - Thrombolysis: evidence for infarct size reduction. PMID- 1903407 TI - Gastric ulcer healing: a comparison of enprostil versus ranitidine. AB - Enprostil is a synthetic prostaglandin E2 analogue with gastric antisecretory and mucosal protective properties. We compared the effects of enprostil and ranitidine on the healing of gastric ulcers and the subsequent relapse rates over 6 months. Patients (N = 156) were recruited for a double-blind study from 12 centers in Europe; 71 were randomly assigned to oral treatment with 35 micrograms enprostil twice daily and 85 to 150 mg ranitidine twice daily for up to 8 weeks. Both groups were of similar demography; their healing rates were also similar. Cumulative intent-to-treat healing rates were at 4 weeks enprostil 48%, ranitidine 41%: at 6 weeks enprostil 65%, ranitidine 68%; and at 8 weeks enprostil 72%, ranitidine 80%. Of those patients who met all protocol criteria and completed treatment, and were endoscoped at the prescribed times, healing rates were at 4 weeks enprostil 55%, ranitidine 54%, at 6 weeks enprostil 75%, ranitidine 84%; and at 8 weeks enprostil 80%, ranitidine 90%. Relief of pain was rapid and similar in both groups. The incidence of adverse events was low and similar in the two groups. The treatment-free relapse rate at 6 months was enprostil 64%, ranitidine 49%; the median times to relapse were 169 and 203 days, respectively. Enprostil and ranitidine appear to be equally effective in healing gastric ulcers. PMID- 1903408 TI - Diarrhea associated with tube feeding: the importance of using objective criteria. AB - Since the published incidence of tube feeding-associated diarrhea varies widely between 2.3 and 68%, and because commonly used definitions of diarrhea are subjective and imprecise, we determined the actual fecal output of malnourished patients during the first 6 days of tube feeding. Nine patients on the same isoosmolar formula were evaluated for diarrhea. Patients were interviewed daily as to whether they thought diarrhea was present or absent. Frequency of defecation was recorded, and stool was collected daily for weight. When assessed subjectively, the incidence of diarrhea rose from 11% on day 1, to 25% on day 4, and to 43% by day 6. The group (n = 4) complaining of diarrhea averaged 3.0 bowel movements per day, whereas those denying diarrhea (n = 5) averaged fewer than 0.2 bowel movements per day (p less than 0.01). Stool weight, however, plateaued for all patients by day 6 at 52.7 +/- 35.7 g of stool per day. No patient produced in excess of 250 g of stool per day. We suggest that traditional subjective measures for assessing diarrhea may be flawed and should not be relied upon when evaluating and treating tube feeding-associated diarrhea. PMID- 1903410 TI - Myelodysplastic syndrome and pancytopenia in a patient with non-A, non-B chronic active hepatitis. AB - Non-A, non-B viral hepatitis may cause many different hematologic abnormalities, such as transient anemia, granulocytopenia, thrombocytopenia, atypical lymphcytosis, or aplastic anemia. We describe a patient who developed a myelodysplastic syndrome (refractory anemia with excess blasts) after prednisone therapy for non-A, non-B chronic active hepatitis. We discuss the effects of non A, non-B viral infection on the bone marrow and potential explanations for the previously unreported association with myelodysplastic syndrome. PMID- 1903409 TI - The effect of oral nitroglycerin on portal blood velocity as measured by ultrasonic Doppler. A double blind, placebo controlled study. AB - We studied the effect of oral nitroglycerin on portal blood velocity (PBV) in 20 cirrhotic patients by a double blind, placebo controlled method using noninvasive Doppler sonography. After we obtained baseline Doppler in the fasting state, 0.6 mg nitroglycerin or placebo was given orally and the mean of 3 s averaged mean PBVs was repeated at 5 min intervals for 60 min. Ten patients each received nitroglycerin or placebo. Portal vein flows were antegrade in all. Of the 10 patients receiving nitroglycerin, seven (P = 0.002) showed a greater than 10% fall in the mean PBVs for at least 15 min. Of these seven "responders," five patients had a 10% decrease in mean systemic blood pressure for at least 15 min. None of the "nonresponders" had systemic hypotension. Our study suggests that the PBV-reducing effect of nitroglycerin in cirrhotics may be explained in part by systemic hypotension. PMID- 1903411 TI - T cell receptor activation induces rapid phosphorylation of prosolin, which mediates down-regulation of DNA synthesis in proliferating peripheral lymphocytes. AB - Prosolin is a major cytosolic phosphoprotein expressed prominently in rapidly proliferating human peripheral lymphocytes but produced at very low levels in resting (G0) PBL. It undergoes rapid phosphorylation upon treatment of growing cells with tumor-producing phorbol esters (TPA) and this phosphorylation event is correlated with a rapid down-regulation of DNA synthesis. In the present report we have studied various agents that, like TPA, act as partial or complete mitogens for G0 PBL and have determined their effect on phosphorylation of prosolin and on DNA synthesis in rapidly proliferating (IL-2-dependent) human PBL. Agents that activate the TCR (OKT3 and PHA), as well as agents that by-pass the receptor but activate biochemical pathways associated with TCR activation (TPA and Ca2(+)-ionophore), all produced rapid phosphorylation of prosolin and prompt down-regulation of DNA synthesis. Four phosphorylated forms of prosolin were produced, indicating activation of a complex phosphorylation pathway. Down regulation of DNA synthesis did not lead to cell death or to permanent arrest, but was reversed after 24 to 48 h, and was not associated with any reduction in overall protein synthesis. Agents that bind to determinants closely connected to the TCR but without activating it (OKT4 and OKT8) had no effect on either prosolin phosphorylation or DNA synthesis. The results indicate that prosolin is an early target of the protein kinase activities induced by activation of the TCR in proliferating PBL, and suggest that its phosphorylation mediates the TCR signal, transmitting it into a biochemical pathway leading specifically to down regulation of DNA synthesis. In G0 PBL, in which the negligible expression of prosolin precludes significant production of phosphorylated species, this inhibitory pathway is effectively blocked. PMID- 1903412 TI - Selective stimulation of human T cells with streptococcal erythrogenic toxins A and B. AB - Streptococcal exotoxins have been implicated in the pathogenesis of a toxic shock like syndrome and scarlet fever. Previous studies have demonstrated that these toxins are potent stimulators of human T cells and have structural homology to staphylococcal enterotoxins. In the current study, we investigated the mechanism by which streptococcal erythrogenic toxins type A (SPEA) and B (SPEB) activate T cells and compared it with anti-CD3 and the known "superantigen" staphylococcal enterotoxin B. SPEA was found to selectively activate T cells bearing V beta 8, V beta 12, and V beta 14, whereas SPEB selectively activated T cells bearing V beta 2 and V beta 8. Furthermore, fibroblasts transfected with MHC class II molecules were capable of presenting SPEA and SPEB to purified T cells. The T cell response to these toxins, however, was not MHC-restricted. Although the streptococcal exotoxins stimulated both CD4+ and CD8+ T cells, SPEA but not SPEB stimulated the CD4+ T cell subset proportionately more than the CD8+ T cell subset. Our results indicate that SPEA and SPEB, like the staphylococcal enterotoxins, are superantigens and suggest a mechanism by which they may mediate particular systemic syndromes associated with streptococcal infections. PMID- 1903413 TI - A novel differentiation antigen on human monocytes that is specifically induced by granulocyte-macrophage colony-stimulating factor or IL-3. AB - A mouse mAb (TOMS-1) was generated against human blood monocytes that had been cultured for 4 days in medium with recombinant human granulocyte-macrophage CSF (GM-CSF). TOMS-1 (IgG1) detected a unique cell surface Ag with a molecular mass of about 43 kDa under both reducing and nonreducing conditions. TOMS-1Ag was expressed on monocytes treated with GM-CSF, but not on fresh or untreated monocytes. This Ag was induced dose dependently during culture of monocytes with GM-CSF for more than 24 h, reaching a maximum level in 3 or 4 days. Treatment of monocytes with cycloheximide in the presence of GM-CSF blocked TOMS-1Ag induction completely, indicating that de novo protein synthesis was required for its expression. TOMS-1Ag was also induced by treatment of monocytes with IL-3, but not with other cytokines such as macrophage-CSF, IL-4, and IFN-gamma or stimulators including LPS, desmethyl muramyl dipeptide, and PMA. TOMS-1Ag expression induced by GM-CSF was up-regulated by IL-4, but down-regulated by IFN gamma. TOMS-1Ag was not induced on lymphocytes, granulocytes, or AM by GM-CSF or appropriate stimuli. TOMS-1Ag was also not expressed on any cell lines of human leukemias or solid tumors examined. Thus, TOMS-1Ag is a monocyte-specific differentiation Ag induced by GM-CSF or IL-3. These results suggest that TOMS-1 should be useful for monitoring the process of monocyte differentiation by GM-CSF or IL-3. PMID- 1903414 TI - Preexposure of macrophages to low doses of lipopolysaccharide inhibits the expression of tumor necrosis factor-alpha mRNA but not of IL-1 beta mRNA. AB - LPS is known to be a potent activator of macrophages and induces the production of TNF-alpha and IL-1. However, the signaling events and regulatory mechanisms required for the activation of macrophages by LPS have not been resolved precisely. We show that LPS modulates its own response in macrophages. Proteose peptone-induced murine peritoneal macrophages (P-PEM) produce significant amount of TNF-alpha and IL-1 after stimulation with LPS. However, preexposure of macrophages to low doses (less than 1 ng/ml) of LPS renders them refractory to stimulation by a second round of LPS, as evaluated by production of TNF-alpha. The loss of sensitivity to a second round of LPS was selective for TNF-alpha production as the LPS-primed macrophages retained the ability to produce IL-1. Northern blot analysis was performed with total RNA obtained from control and LPS (1 ng/ml) primed P-PEM after 3-h stimulation with a second round of LPS. The expression of TNF-alpha mRNA was inhibited in LPS-primed P-PEM, whereas the expression of IL-1 beta mRNA was the same in control and LPS-primed P-PEM, consistent with the data of biologic activities of these two cytokines. Zymosan induced TNF-alpha production was the same in control and LPS-primed macrophages, indicating that not all of the pathways required for TNF-alpha production were affected by LPS priming. Monokines such as human (h) rIL-1 alpha, hrTNF-alpha, hrIL-6, and murine rIFN-beta could not substitute for the action of low doses of LPS, and addition of indomethacin could not restore TNF-alpha production. These results suggest that exposure of macrophages to low doses of LPS suppresses the production of TNF-alpha, but not of IL-1, by inhibiting the expression of mRNA through a noncyclooxygenase-dependent mechanism. Thus, LPS-induced production of TNF-alpha and IL-1 in macrophages are differently regulated. PMID- 1903415 TI - IFN-gamma inhibits development of Plasmodium berghei exoerythrocytic stages in hepatocytes by an L-arginine-dependent effector mechanism. AB - Primary cultures of BALB/cJ hepatocytes treated with 10(3) U/ml rIFN-gamma consistently inhibited intracellular Plasmodium berghei liver schizont development by 50 to 70%. Monomethyl-L-arginine (NGMMLA), the competitive inhibitor of L-arginine as substrate for production of nitric oxides by hepatocytes, reversed the activity of IFN-gamma on these malaria-infected cells. Reversal of IFN-gamma activity by NGMMLA was dose dependent and was maximal at 0.5 mM NGMMLA. Depletion of L-arginine by addition of arginase to the culture medium blocked the capacity of IFN-gamma to inhibit parasite development in hepatocytes; addition of excess L-arginine to cultures treated with IFN-gamma in the presence of NGMMLA competitively restored IFN-gamma capacity to activate hepatocyte anti-parasite activity. TNF-alpha was neither required for IFN-gamma activity, nor effective at any concentration tested as an inhibitor of schizont development by itself in primary hepatocytes. These data strongly suggest that the action of IFN-gamma on P. berghei-infected hepatocytes is to induce the production of L-arginine-derived nitrogen oxides that are toxic for the intracellular parasite. PMID- 1903416 TI - Upstream elements of the MHC class II E beta gene active in B cells. AB - The MHC class II (Ia) molecules are heterodimeric cell surface glycoproteins that have a limited tissue distribution and are essential for an Ir. These proteins are known to both display a limited tissue distribution and be responsive to up regulation by cytokines such as IL-4. To begin to identify the molecular basis for both of these phenomena in B cells, we performed a deletional analysis of the upstream region of the murine E beta gene. We show that there are several cooperating positive as well as negative control elements in the E beta upstream region. The sequence between -2679 and -66 is a strong transcriptional element containing several sequences that act synergistically as positive elements. The negative elements are located more proximal to the transcription start site. Furthermore, two consensus motifs, termed X and Y, which are located in the proximal upstream region of all class II genes, are necessary for the transcriptional activity of more distal elements. Additionally, we identify an IL 4-responsive element located within 666 bp upstream of the transcription initiation site. PMID- 1903417 TI - Transforming growth factor-beta suppresses human B lymphocyte Ig production by inhibiting synthesis and the switch from the membrane form to the secreted form of Ig mRNA. AB - Transforming growth factor-beta (TGF-beta) inhibits B cell Ig secretion and reduces B cell membrane Ig expression. The addition of TGF-beta to human B lymphocyte cultures stimulated with Staphylococcus aureus Cowan strain I and IL-2 completely inhibited B cell Ig secretion (greater than 90%) and decreased B cell surface IgM, IgD, kappa L chain, and lambda L chain expression. In contrast, TGF beta had only minimal effects on two other B cell membrane proteins, HLA-DR and CD20. Internal labeling with [35S]methionine and immunoprecipitation with anti IgM, anti-kappa, and anti-lambda antibodies revealed a striking reduction in kappa L chain in the presence of TGF-beta. A less pronounced reduction in lambda L chain and microH chain was also noted. Northern blot analysis of RNA purified from B cells treated with TGF-beta for varying time intervals revealed a significant decrease in steady state kappa and lambda L chain mRNA levels. Furthermore, a significant decrease in the switch from the membrane forms of mu and gamma to their respective secreted forms was noted in the presence of TGF beta. Nuclear run-on experiments demonstrated decreased transcription of kappa L chain. The effects of TGF-beta on two transcriptional regulatory factors, Oct-2 and nuclear factor (NF) kappa B, known to be important in Ig gene transcription were examined. Oct-2 mRNA levels and both Oct-2 and NF-kappa B proteins in nuclear extracts were not altered by treatment with TGF-beta. In contrast, levels of the transcriptional factor AP-1, which is not known to be important in B cell Ig production, were reduced by TGF-beta. These findings demonstrate that TGF-beta decreases B lymphocyte Ig secretion by inhibiting the synthesis of Ig mRNA and inhibiting the switch from the membrane form to the secreted forms of mu and gamma mRNA. The mechanism by which TGF-beta inhibits Ig chain synthesis is unclear although it does not involve inhibition of the binding of NF-kappa B or Oct-2 to their respective target sequences. PMID- 1903418 TI - Sequence of C region of L chains from Xenopus laevis Ig. AB - A cDNA expression library, prepared from Xenopus laevis splenocytes, was screened with antibodies to Xenopus Ig. One clone, lambda XIg23, reacted with antibodies to IgY and to IgM; the insert hybridized to approximately 1.3-kb RNA from spleen, the approximate size expected for L chain mRNA. An additional clone, lambda XIg31, was identified by cross-hybridization. The inserts of lambda XIg23 and lambda XIg31 begin in the third framework region of the V region and extend through the C region to the poly(A) tail. Except for a single nucleotide difference, the two C region sequences are identical. The amino acid sequence of the C region was compared with the sequences of a variety of C kappa and C lambda, as well as to C region sequences of L chains from Rana catesbeiana and from two species of shark. The Xenopus C region resembles mouse and human C kappa slightly more than C lambda. The similarity of the Xenopus and Rana C regions to each other is approximately the same as that of either amphibian sequence to mammalian CL. The data are discussed in terms of the evolution of kappa and lambda C regions. PMID- 1903419 TI - Identification of a new V kappa gene family that is highly expressed in hybridomas from an autoimmune mouse strain. PMID- 1903420 TI - Improved permeabilization procedure for flow cytometric detection of internal antigens. Analysis of interleukin-2 production. AB - A cell membrane permeabilizing treatment is described which involves the use of lysolecithin at low concentration in acidic acetate buffer and paraformaldehyde fixation. It preserved well-separated scatter cytograms of small and large lymphocytes. The accuracy of the immunochemical detection of internal antigens by flow cytofluorography was demonstrated by the linear relationship between the percentage of fluorescent cells detected and the proportion of intracellular antigen-containing cells in mixtures with antigen-negative cell lines. Cell cycle analysis by dual nuclear staining with propidium iodide and FITC-conjugated Ki-67 antibody recognising in vitro stimulated human T lymphocytes verified that the proliferating lymphocytes retained their increased light scatter properties after permeabilization. Enumeration of interleukin-2 (IL-2) producing cells by their cytoplasmic immunofluorescence showed that enlarged lymphocytes were the main IL 2 producing cells. This improved permeabilization procedure, by gating small and enlarged lymphocytes separately, makes it possible to determine by two color fluorescence the immunophenotype of activated T cells committed to interleukin production. PMID- 1903421 TI - Effect of praziquantel on pancreatic histopathological changes in experimental schistosomiasis mansoni. AB - The pancreatic tissue showed deposition of S. mansoni eggs on the 8th week of infection, multiple granulomata, interstitial oedema, inflammatory infiltrate, acinar atrophy and decrease in the size of islets of Langerhans. It was found that the most effective dose of praziquantel in such changes was 300 mg/kg/mouse, irrespective of being administered once or in three divided doses every four hours in the same day. PMID- 1903422 TI - Study of the possibility of placental involvement in experimental bilharziasis. AB - Twenty-five female golden hamsters were divided into three groups. The first group was infected before mating, sacrifice was done to perform worm perfusion and histopathological examination of the liver and placenta. The second group was infected in early pregnancy and sacrificed before delivery. The third group was the control normal pregnant group. The results showed that the infection rate was 28%. Pathological examination of the first group showed that although the liver had attained the full histopathological picture of bilharziasis yet the placenta was found to be free from that infection. That might be due to short duration of placental formation in hamsters, and lack of anastomotic channels between the placenta and the portal circulation. In the second group no bilharzial affection could be detected in the placenta or the liver as sacrifice was done before worm maturation. Also, it could be assumed that acute bilharziasis did not lead to complication of pregnancy in golden hamsters as no abortion happened during this study. PMID- 1903423 TI - Effect of praziquantel therapy on testes of mice infected with Schistosoma mansoni. AB - Histopathological changes in the testes of mice infected with S. mansoni before and after praziquantel therapy in early infection and late infection were studied. In early infection, 150 mg/kg of praziquantel regimen gave a very good effect comparable with 300 mg/kg dose. In both regimens the testes returned almost to normal activity after treatment. In late infection 150 mg/kg of praziquantel gave moderate improvement in spermatogenic activity compared to almost complete cure and return to full activity with 300 mg/kg praziquantel regimens. Also, any possible side effects of the drug on the testicles were looked for. The present study proved the safety use of the drug as regard to its testicular effects. PMID- 1903424 TI - Immunoglobulin pattern of schistosomiasis mansoni in patients with chronic renal failure. AB - In hepatosplenic Schistosomiasis with chronic renal failure, it was found that the serum immunoglobulin G and M show significant increase while there was a controversy about IgA. In chronic renal failure without Schistosomiasis, it was found that the immunoglobulin G, M and A levels show non-significant changes. PMID- 1903425 TI - Immunohistochemical characterization of T-lymphocytes subsets in Egyptian hepatic schistosomiasis. AB - Liver biopsies from 20 schistosomal patients in the compensated stage were studied by immunoalkaline phosphatase technique for the relative distribution of T-cell subpopulations. T-cell subsets were defined for OKT3 (+) (pan T lymphocytes), OKT4 (+) (helper-inducer), and OKT8 (+) (suppressor-cytotoxic) cell by using mouse hybridoma monoclonal antibodies. Sections showed marked pan T lymphocytic infiltration predominantly in the portal tract within liver lobules and in the granulomatous lesions. Marked relative increment of suppressor/cytotoxic OKT8 (+) lymphocytes over the helper/inducer OKT4 (+) were observed. Alkaline phosphatase activity showed inverse significant correlation with OKT3 (+) and OKT8 (+) % and a direct significant correlation with OKT4 (+) % lymphocytes. This may suggest that suppressor cytotoxic OKT8 lymphocytes may be responsible for the modulation of the granulomata and stabilization of the morbidity state. PMID- 1903426 TI - Effect of splenectomy on cell mediated immunity in bilharzial patients with splenomegaly. AB - The effect of splenectomy on cell mediated immunity was studied in 15 male patients with mean age 28 years +/- 9 s.d. with bilharzial splenomegaly and oesophageal varices, for comparison, ten healthy control males with mean age 28 years +/- 4 s.d. were included. The cellular immune response was assessed before and one month after splenectomy. The assessment included the enumeration of T lymphocyte subsets in vitro using monoclonal antibodies and in vivo by intradermal skin test for delayed reaction using specific Schistosoma mansoni adult antigen and non specific purified protein derivatives (P.P.D.). The result showed that the possibility of the delayed skin reaction was higher after splenectomy, also there was an increase in the number of T helper cells and reduction in number of T suppressor cell but the number of pan T cell did not significantly change. This result indicates that the ratio of T helper/T suppressor ratio improved after splenectomy with a concomitant improvement of the immunological response of the patients. PMID- 1903427 TI - Most peripheral B cells in mice are ligand selected. AB - Using amplified cDNA and genomic libraries, we have analyzed the VH gene repertoire of pre-B cells and various B cell subsets of conventional mice at the level of VH genes belonging to the J558 VH gene family. The sequence data were evaluated on the basis of a newly established list of 67 J558 VH genes that comprise approximately two-thirds of the J558 VH genes of the murine IgHb haplotype. The results of the analysis demonstrate that VH gene utilization in pre-B cells, although biased to some extent by B cell autonomous VH gene selection, scatters over the whole range of J558 VH genes present in the germline. In contrast, in mature, peripheral B cells comprising long-lived mu + delta high B cells as well as Ly-1 B cells, small overlapping sets of germline VH genes are dominantly expressed. The data indicate that the recruitment of newly generated B cells into the long-lived peripheral B cell pool is mediated through positive selection by internal and/or external antigens. Because of the absence of immunoglobulin class switching and somatic hypermutation, this process is different from the selection of memory B cells in T cell-dependent immune responses. PMID- 1903428 TI - The gene coding for a major tumor rejection antigen of tumor P815 is identical to the normal gene of syngeneic DBA/2 mice. AB - We showed previously that mouse mastocytoma P815 expresses several distinct antigens that are recognized by cytolytic T lymphocytes (CTL) of syngeneic DBA/2 mice. Antigens P815A and P815B are usually lost jointly and are targets for immune rejection responses in vivo. We used a cosmid library and a CTL stimulation assay to obtain transfectants expressing tumor rejection antigen P815A. From these transfectants we retrieved gene P1A which transferred the expression of both P815A and B. This gene is unrelated to three previously isolated genes coding for tum-antigens. It encodes a putative protein of 224 amino acids which contains two highly acidic domains showing homology with similar regions of nuclear proteins. The P1A gene expressed by tumor P815 is completely identical to the gene present in normal DBA/2 cells. Expression of the gene was tested by Northern blots. Cells from liver, spleen, and a number of mast cell lines were negative, but mast cell line L138.8A produced a high level of P1A message and was lysed by CTL directed against antigens P815A and B. We conclude that major tumor rejection antigens of P815 are encoded by a gene showing little or no expression in most normal cells of adult mice. PMID- 1903429 TI - Trans-splicing as a possible molecular mechanism for the multiple isotype expression of the immunoglobulin gene. AB - We analyzed the molecular mechanism for the immunoglobulin (Ig) multiple isotype expression using a transgenic mouse (TG.SA) model system. Though most of the endogenous mu chain expression was excluded by the expression of the human rearranged mu transgene in the TG.SA mouse, a significant portion of splenic B lymphocytes could express the transgenic human IgM and endogenous mouse IgG simultaneously after stimulation with lipopolysaccharide and interleukin 4. The fluorescence-activated cell sorter-purified population of the human IgM+/mouse IgG+ cells expressed mRNA that consisted of properly spliced sequences of the transgenic VHDJH and the endogenous mouse C gamma genes (trans-mRNA), together with the transgenic human mu mRNA and germline transcripts of the mouse C gamma gene, without apparent rearrangement of the transgene. We also found that a lymphoma tumor, derived from the cross between the TG.SA mouse and another transgenic mouse carrying Ig H chain enhancer-driven c-myc oncogene, expressed about equal levels of the trans-mRNA and the transgenic mu mRNA without DNA rearrangement in either the transgene or the endogenous mouse switch region. These findings strongly support our previous proposal that the trans-splicing can account for the multiple isotype expression in this transgenic model and also suggest that novel molecular mechanism(s) might be involved in this reaction. PMID- 1903430 TI - In situ expression and localization of Neisseria gonorrhoeae opacity proteins in infected epithelial cells: apparent role of Opa proteins in cellular invasion. AB - During natural infection, gonococcal opacity proteins (Opa) undergo rapid phase variation, but how this phenomenon contributes to the virulence of the bacteria is not well understood. In the present immunomorphological study we examined the actual Opa status of individual gonococci during various stages of gonococcal infection of Chang epithelial cells, by probing ultrathin sections of infected specimens with Opa-specific monoclonal antibodies. Our results demonstrate a heterogeneous Opa expression during the initial interaction of the bacteria, but an almost 100% expression of one of the probed Opas during their secondary attachment and entry into the host cells, suggesting a role for distinct Opas in cellular penetration. The association between Opa expression, tight attachment, and bacterial invasion into the host cells could be confirmed with isogenic variants that expressed different Opa proteins. Once inside the epithelial cells, both morphologically intact, Opa positive and morphologically disintegrated, Opa negative bacteria were observed. The loss of Opa immunoreactivity in intracellular gonococci could not be related to the presence of a particular Opa protein, but could be mimicked by incubating the organisms with extracts of sonicated uninfected epithelial cells, suggesting that it was caused by host cell proteolytic activity. Taken together, our data suggest that Opa phase transitions confer a functional adaptation of the bacteria enabling host cell penetration. PMID- 1903432 TI - Identification of the promoter and the transcriptional start site of the spoVA operon of Bacillus subtilis and Bacillus licheniformis. AB - The region upstream of the coding sequence of the spoVA operon was studied by several techniques to identify the promoter and to determine the start point for transcription of spoVA. The results of plasmid integration analysis in Bacillus subtilis showed that no more than 119 bp upstream of the coding sequence is needed for expression. A comparison of the sequence of this upstream region with the corresponding sequence from Bacillus licheniformis showed four stretches that were perfectly conserved, interspersed with poorly conserved stretches; the second and third of these conserved stretches appeared to represent the '-35' and '-10' regions of a promoter recognized by RNA polymerase containing sigma G. Primer extension analysis in B. subtilis revealed a spoVA transcript which had apparently initiated 6 bp downstream of the putative '-10' heptanucleotide CATACTA, that is, 27 bp upstream of the coding sequence. This transcript was observed 4 h and 5 h after the initiation of sporulation, but not at earlier times. PMID- 1903433 TI - Permeability of dormant spores of Bacillus subtilis to malachite green and crystal violet. AB - The permeability of dormant spores of Bacillus subtilis to malachite green (MG) and crystal violet (CV) was examined by using potassium trichloro(eta 2 ethylene)platinum(II) (KTPt) as an electron-opaque marker for the dyes. The spores were treated with the dyes and other substances at 30 degrees C for 30 min or at 80 degrees C for 5 min. When the spores were incubated in 50 mM-MG solution at 30 degrees C and in 50 mM-CV solution at 30 degrees C or 80 degrees C, many small electron-dense precipitates, which were chemical complexes of dyes and platinum, were seen, mainly around the boundary between the inner and outer coat regions. The spores treated under the above conditions were not stained. Treatment with 50 mM-MG alone or a mixture of 25 mM-oxalic acid and 50 mM-CV at 80 degrees C made the spores stainable and dye-TPt precipitates were observed mainly in the outer pericortex region. Pretreatment with 25 mM-oxalic acid and 5% (v/v) phenol at 80 degrees C followed by 50 mM-CV treatment at 30 degrees C gave the same results as above. It was considered from these results that the inner coat itself might function as the primary permeability barrier to MG and CV, and that a secondary barrier to the dyes might exist around the cortex region. PMID- 1903431 TI - Structure and expression of human germline VH transcripts. AB - The human VH5 family consists of two functional genes and one pseudogene. We have found a novel 1.2-kb VH5 gene transcript in normal fetal liver and cord blood and in transformed B lineage cells. VH5-positive cDNA clones were isolated from precursor B acute lymphoblastic leukemia, B chronic lymphoblastic leukemia, Epstein-Barr Virus-transformed B cell lines, and cord blood, and were identified as transcripts of unrearranged VH5 genes (germline transcripts). The cDNA clones were derived from both functional and pseudo-VH5 genes. Most germline transcripts appear to initiate at the normal VH promoter and are cleaved and polyadenylated at sites several hundred bases downstream of the VH5 coding region. Correct splicing of the leader intron was observed in all clones. In functional and pseudo-VH5 cDNAs, an open translational reading frame extends from the leader to a termination codon in the nonamer. Only limited polymorphisms were observed in the coding as well as flanking regions of the VH5 transcripts. Functional and pseudo-VH5 transcripts and previously identified murine germline VHJ558 transcripts are discussed. PMID- 1903434 TI - Occurrence of a novel yeast enzyme, L-lysine epsilon-dehydrogenase, which catalyses the first step of lysine catabolism in Candida albicans. AB - The yeast Candida albicans is able to utilize L-lysine as the sole nitrogen and carbon source accompanied by intracellular accumulation of alpha-aminoadipate delta-semialdehyde. A novel yeast amino acid dehydrogenase catalysing the oxidative deamination of the epsilon-group of L-lysine was found in this yeast. The enzyme, L-lysine epsilon-dehydrogenase, is strongly induced in cells grown on L-lysine as the sole nitrogen source. The enzyme is specific for both L-lysine and NADP+. The Km values were determined to be 0.87 mM for L-lysine and 0.071 mM for NADP+. An apparent Mr of 87,000 was estimated by gel filtration. The enzyme has maximum activity at pH 9.5 and a temperature optimum of 32 degrees C under our assay conditions. PMID- 1903435 TI - Comparison of proteins of simian herpesvirus aotus type 2 and bovine herpesvirus type 4. AB - Genomes of herpesvirus aotus type 2 (HVA-2) and bovine herpesvirus type 4 (BHV-4) have previously been shown to be closely similar. Moreover, preliminary serological data indicated that HVA-2 is antigenically related to BHV-4. To extend this study, structural components of four BHV-4 strains and HVA-2 were compared by SDS-PAGE, radioimmunoprecipitation and Western blotting. The overall pattern of structural proteins was the same for HVA-2 and BHV-4 but variations were observed in electrophoretic profiles of glycoproteins, mainly of the two major ones (gp6/gp10/gp17 and gp11/VP24). Variations between HVA-2 and BHV-4 glycoproteins were greater than those observed among BHV-4 strains. PMID- 1903436 TI - Effects of ionic strength on endogenous nuclease activity in chelated and nonchelated chromatin. AB - Calf thymus chromatin, isolated using a standard (low ionic strength, but nonchelating) isolation protocol, dialyzed against either Tris-PMSF or Tris-EDTA, was reconstituted in a high salt compacting buffer (COM) or a low salt dispersing buffer (DIS) prior to digestion with endogenous nucleases. A greater level of enzyme activity occurred when chromatin was in a condensed state (COM buffer) and not chelated prior to digestion. In contrast, chromatin chelated by dialysis against Tris-EDTA prior to digestion showed higher levels of enzyme activity in the dispersed state (DIS buffer). Nonchelated undigested chromatin contained 0.280 +/- 0.16 ug copper/mg DNA and and 0.305 +/+- 0.09 ug zinc/mg DNA. Chelation removed about 78% of copper per mg DNA and approximately 65% of zinc per mg DNA. In COM buffer after a 20 min digestion, the solubilized fraction was enriched in copper showing about 20 X more metal per mg DNA than nonchelated chromatin. Approximately the same amount of zinc was found in both chelated and nonchelated chromatin while there was less zinc in chelated chromatin solubilized in DIS buffer. Thus, chelation has important effects on the digestibility of chromatin and on the type of ionic environment that provides the most favorable conditions for endogenous nuclease activity. PMID- 1903437 TI - Stimulation of myoblast proliferation in culture by leukaemia inhibitory factor and other cytokines. AB - Significant stimulation of growth of myoblasts in culture is achieved by leukemia inhibitory factor (LIF). The optimum activity of this cytokine occurs at about 6 pM LIF. Interleukin-6 (IL-6) also stimulates cultured myoblasts but to a lesser degree than LIF and the effect is not maintained for extended culture periods. In addition, transforming growth factor-alpha (TGF-alpha) also increases the growth rate of myoblasts but only after a considerable lag phase. All 3 cytokines may be of value in the large scale production of myoblasts for use in the potential treatment of primary myopathies by injection of cultured myoblasts into diseased muscle to form genetically complete muscle fibres after fusion of the myoblasts in situ. Their potential use is enhanced in that at least under the conditions used here they do not stimulate fibroblast proliferation. PMID- 1903438 TI - Dopa and dopamine cause cultured neuronal death in the presence of iron. AB - We examined the cytotoxicity of dopa and dopamine for cultured neurons by using a newly developed enzyme immunoassay for neurofilament protein to determine surviving neuronal numbers. Each of the two catechols caused neuronal death in the presence of iron with or without superoxide dismutase and catalase, while deferoxamine mesylate prevented neuronal loss. Lipid peroxidation of phospholipid liposomes was confirmed to be produced by the combination of the catechols and iron (Fe3(+)-ADP complex). Thus, it was strongly suggested that cultured neurons were killed via the peroxidative cleavage of cell membrane components provoked by the catechols and iron. This mechanism of neuronal loss may play an important role in the degeneration in the substantia nigra of Parkinson's disease, because the catechols and iron are abundant in this region. PMID- 1903439 TI - Increased MR signal intensity due to cervical myelopathy. Analysis of 29 surgical cases. AB - The cases of 29 patients with cervical myelopathy, who had been treated by anterior spine fusion, were reviewed. The relationship between pre- and postoperative magnetic resonance (MR) images was investigated with special reference to increased signal intensity in the spinal cord on the T2-weighted images and the relevance of this finding to clinical conditions. Preoperatively, there were areas of increased signal intensity in 12 patients whereas there were no areas of increased signal intensity in the other 17. The lesions were not clearly demonstrated on T1-weighted images. The pre- and postoperative clinical condition of the patients whose preoperative MR images showed areas of increased signal intensity in the spinal cord on T2-weighted images was worse than that of the patients who did not have areas of increased signal intensity. Of the 12 patients with regions of increased signal intensity preoperatively, five showed decreased signal intensity postoperatively compared to the preoperative levels and seven had no change. The postoperative recovery of the five patients who showed decreased signal intensity postoperatively was better than that of the seven patients who exhibited no change. The areas of increased MR signal in the spinal cord might be due to edema, cord gliosis, demyelination, or microcavities. PMID- 1903440 TI - Nutrient utilization by cells isolated from rat jejunum, cecum and colon. AB - Cells isolated from the jejunum, cecum and colon of rats were used to study the oxidation of nutrients by quantifying the production of 14CO2 from 5 mmols/L 14C labeled exogenous substrate. In colonic cells, the decreasing order of oxidation was as follows: butyrate greater than acetate greater than propionate, glucose and glutamine. Acetate and butyrate significantly suppressed oxidation of both glucose and glutamine. In cells taken from the cecum, butyrate was oxidized at a greater rate than all other substrates. Cells taken from the jejunum produced CO2 from exogenous substrates in decreasing order as follows: glutamine greater than glucose much greater than acetate, propionate and butyrate. Butyrate oxidation was significantly reduced in colonic cells by 3-hydroxybutyrate, and it was reduced in cecal cells by glucose. Comparisons among the three gut segments showed no differences in glutamine oxidation. Glucose oxidation was greater in cells taken from the colon than from the cecum or jejunum, which were similar. Butyrate and acetate were oxidized at higher rates in cells taken from the cecum and colon than in cells taken from the jejunum, and propionate was oxidized at a greater rate in cells taken from the colon than from the jejunum. These studies demonstrate that relative rates of substrate oxidation differ along the intestinal tract of rats. PMID- 1903441 TI - Latest advances in thrombolytic therapy. AB - Despite recent advances in scientific knowledge and the use of sophisticated medical technology, cardiovascular disease remains the leading cause of death in the United States. Thrombolytic therapy offers an exciting modality in the treatment of thromboembolic diseases, especially myocardial infarction. By lysing coronary thrombi early in the evolution of the infarction process, thrombolytic therapy can be an effective means of limiting infarction size and preserving myocardial function. Intravenous nurses play an essential role in promoting the maximal benefits of thrombolytic agents while ensuring patient safety. PMID- 1903442 TI - The expression of c-fos protein in human breast. AB - The expression of the c-fos protein has been examined in non-malignant and malignant human breast using immunohistochemistry. Since in some cell types expression is associated with differentiation, while in other cells induction is related to growth, the extent of reactivity in carcinomas has been related to tumour grade, oestrogen receptor, epidermal growth factor receptor, and Ki-67 staining. There was a greater degree of staining in the carcinomas than in the normal and benign tissue. In the latter, there was no relationship with menopausal status or with extent of proliferative changes. In all instances, staining was nuclear. Poorly differentiated carcinomas had a greater degree of reactivity, but the converse did not apply to the well differentiated tumours. There was no relationship with oestrogen receptor, epidermal growth factor receptor, or Ki-67 labelling. The greater expression observed in carcinomas correlates with previously reported RNA studies. There is no clear relationship between c-fos protein detection and proliferation or differentiation. PMID- 1903443 TI - Apoptosis induced by mild hyperthermia in human and murine tumour cell lines: a study using electron microscopy and DNA gel electrophoresis. AB - Mild hyperthermia is known to enhance apoptosis in a range of normal and neoplastic cell populations. Studies of tumours previously shown to respond to heating in this manner might be expected to provide insights not only into the mechanism of hyperthermic cell killing, but also into the apoptotic process in general. In the present study, cell death induced by 43 degrees C heating for 30 min in two human Burkitt's lymphoma lines, BM 13674 and WW1, and in murine mastocytoma P-815 x 2.1 was found to be exclusively apoptotic in type, identification being based on light and electron microscopic appearances and on the presence of internucleosomal cleavage of DNA into fragments that are multiples of 180-200 base pairs, which was demonstrated by agarose gel electrophoresis. The heat-induced apoptosis was prevented by the presence of zinc sulphate, an inhibitor of the endonuclease considered to be responsible for the DNA cleavage, but was not suppressed by the protein synthesis inhibitor cycloheximide. The findings question the validity of the widely held view that active protein synthesis is an invariable prerequisite for the execution of apoptosis. It is suggested that an inositol triphosphate-mediated increase in cytosolic Ca2+, resulting from limited membrane damage, might be the critical event responsible for activation of apoptosis by mild hyperthermia. PMID- 1903444 TI - Decrease in the size of tetanic responses produced by nitrendipine or by extracellular calcium ion removal without blocking twitches or action potentials in skeletal muscle. AB - The effects of removing extracellular Ca++ ions or of adding the organic calcium channel antagonist, nitrendipine, were tested on twitches and tetani (100 Hz for 2 sec) in frog toe muscles. Under conditions that did not reduce or that potentiated twitches, both procedures reduced the size of the tetanic responses. This depression was seen as an inability to maintain the maximum tetanic tension for more than 0.5 sec. Intracellular microelectrode recordings showed that the muscle fibers were depolarized (mean about 23 mV) during the stimulus train and the fiber only slowly repolarized after the train. The latter effect is the "late negative afterpotential" and it is produced by the accumulation of K+ ions in the t-tubules during the action potential train. Neither the depolarization nor the late negative afterpotentials were decreased in amplitude by nitrendipine. These results indicate that the voltage-sensitive, slow Ca++ channels are opened by the accumulation of K+ ions in the t-tubules during the tetanus and that the Ca++ ions entering via these channels are required to maintain the full strength of the tetanic contraction. It is suggested that this is a function of these Ca++ channels concentrated in the t-tubules of skeletal muscle fibers. PMID- 1903445 TI - Interactions of [3H]amphetamine with rat brain synaptosomes. I. Saturable sequestration. AB - Previous studies have identified a saturable site of d-[3H]amphetamine sequestration (AMSEQ) in rat brain synaptosomes. The present study characterized AMSEQ with respect to its subcellular, neuronal and regional distributions, ontogenetic development, pharmacological specificity and factors required for its maintenance. Although AMSEQ was reduced when assays were performed in Krebs' buffer incubated at 37 degrees C as compared to assays performed in isotonic Tris sucrose buffer incubated at room temperature, the pharmacological profiles of AMSEQ were virtually identical under both conditions. AMSEQ was negligible in tissues outside the central nervous system, enriched in synaptosomes and partially reduced by striatal kainic acid lesion, indicating neuronal localization. The distribution of AMSEQ in the central nervous system was heterogenous. Highest levels were present in hypothalamus with progressively lower levels noted in parietal cortex, frontal cortex, striatum, thalamus, hippocampus, midbrain, cerebellum, pons-medulla and spinal cord. With regard to its ontogeny, AMSEQ increased early in neonatal life, reaching adult levels by postnatal day 14. Although the effects of amphetamine to abolish the transynaptosomal pH gradient suggest a possible role for this gradient in the maintenance of AMSEQ, the pharmacological profile of AMSEQ indicates that other factors are involved. An interaction with an intrasynaptosomal acid, such as N acetylaspartate, may account for AMSEQ maintenance. AMSEQ did not possess a stereospecific preference for either d-(IC50 = 177 microM) or I-amphetamine (IC50 = 173 microM). However, the pharmacological profile of AMSEQ indicated structural specificity with antidepressants being relatively potent inhibitors. The saturation analysis and pharmacological characteristics of AMSEQ (i.e., low affinity and lack of stereospecificity) suggest that AMSEQ may be related to high dose, nonstereospecific effects of amphetamine, such as stereotypy in rats and psychosis in humans. The relative high potency of antidepressants in inhibiting AMSEQ suggests the importance of this phenomenon in the therapeutic effects of these drugs. Furthermore, the link between antidepressants and AMSEQ may provide insight into the comorbidity of major depression and drug abuse. PMID- 1903446 TI - Interactions of [3H]amphetamine with rat brain synaptosomes. II. Active transport. AB - The accumulation of 5 nM d-[3H]amphetamine (d-[3H]AMPH) into rat brain synaptosomes was examined using physiological buffer conditions. The accumulation of d-[3H]AMPH into striatal synaptosomes was saturable, of high affinity, ouabain sensitive and temperature-dependent, suggesting an active transport phenomenon. Eadee-Hofstee analysis of striatal d-[3H]AMPH transport (AMT) saturation isotherms indicated an apparent Km of 97 nM and a Vmax of 3.0 fmol/mg tissue/min. Lesion of the striatal dopaminergic innervation led to equivalent decreases of [3H] dopamine (DA) transport and AMT, indicating that AMT occurs in DA terminals. Furthermore, AMT was not evident in cerebral cortex, a brain region with a paucity of DA terminals. In competition studies, AMT was stereospecific; d-AMPH (IC50 = 60 nM) was an 8-fold more potent inhibitor of the transport than its I isomer (IC50 = 466 nM). DA(IC50 = 257 nM), DA uptake blockers and substrates were found to be potent inhibitors of AMT: GBR12909 IC50 = 5 nM; methamphetamine IC50 = 48 nM; methylphenidate IC50 = 53 nM; and cocaine IC50 = 172 nM. In contrast, serotonin was relatively weak in inhibiting AMT (IC50 = 7.9 microM). There was a highly significant (P less than .001; slope = 1.2) linear correlation between the AMT-inhibiting potencies of AMPH analogs and their potencies in stimulating locomotor activity in rodents. AMT may be important in the low dose effects of AMPH such as increased locomotor activity in rodents and stimulant activity in man. Differences between AMT and d-[3H]AMPH sequestration described earlier, as well as their possible relevance to behavioral and neurochemical sequelae of AMPH administration are also discussed. PMID- 1903447 TI - Quantitative autoradiography of the binding sites for [125I] iodoglyburide, a novel high-affinity ligand for ATP-sensitive potassium channels in rat brain. AB - We have developed a high specific activity ligand for localization of ATP sensitive potassium channels in the brain. When brain sections were incubated with [125I]iodoglyburide (N-[2-[[[(cyclohexylamino)carbonyl]amino]sulfonyl]ethyl] 5-125I-2- methoxybenzamide), the ligand bound to a single site with a KD of 495 pM and a maximum binding site density of 176 fmol/mg of tissue. Glyburide was the most potent inhibitor of specific [125I]iodoglyburide binding to rat forebrain sections whereas iodoglyburide and glipizide were slightly less potent. The binding was also sensitive to ATP which completely inhibited binding at concentrations of 10 mM. Autoradiographic localization of [125I]iodoglyburide binding indicated a broad distribution of the ATP-sensitive potassium channel in the brain. The highest levels of binding were seen in the globus pallidus and ventral pallidum followed by the septohippocampal nucleus, anterior pituitary, the CA2 and CA3 region of the hippocampus, ventral pallidum, the molecular layer of the cerebellum and substantia nigra zona reticulata. The hilus and dorsal subiculum of the hippocampus, molecular layer of the dentate gyrus, cerebral cortex, lateral olfactory tract nucleus, olfactory tubercle and the zona incerta contained relatively high levels of binding. A lower level of binding (approximately 3- to 4-fold) was found throughout the remainder of the brain. These results indicate that the ATP-sensitive potassium channel has a broad presence in the rat brain and that a few select brain regions are enriched in this subtype of neuronal potassium channels. PMID- 1903448 TI - Bacterial contamination in reversible hydrocolloid conditioning units. AB - Four hydrocolloid conditioning units were randomly tested for bacterial contamination. All were contaminated beyond the United States Army's acceptable limit of potability. The predominant bacteria were identified. A discussion of clinical significance and proposals for aseptic technique are presented. PMID- 1903449 TI - Nutritional strategies in cystic fibrosis: current issues. PMID- 1903450 TI - 5-Lipoxygenase inhibitors: the synthesis and structure-activity relationships of a series of 1-phenyl-3-pyrazolidinones. AB - A series of analogues of the 5-lipoxygenase inhibitor 1-phenyl-3-pyrazolidinone (phenidone, 1a) has been prepared via two complementary new synthetic methods. The reaction of various electrophiles with the dianion of 1a or with an N silylpyrazolidinone anion gave the desired 4-substituted pyrazolidinones (Scheme I and II). A new procedure was developed for the resolution of 4-substituted pyrazolidinones (Scheme V). A regression study on 21 compounds in this series showed a correlation of increased inhibitor potency (pIC50) with increased compound lipophilicity (log P) and with an N-phenyl electronic effect as measured by the 13C NMR chemical shift parameter CNMR1' (R2 = 0.79). The most potent 5 lipoxygenase inhibitor in this series was 4-(ethylthio)-1-phenyl-3-pyrazolidinone (1n) with an IC50 of 60 nM. Another member of this series, 4-(2-methoxyethyl)-1 phenyl-3-pyrazolidinone (1f, IC50 = 0.48 microM), although less potent than 1n, was better tolerated in the whole animal relative to phenidone (1a) and also displayed good oral activity in two models of 5-lipoxygenase inhibition. On the basis of a structure-activity relationship study, a mechanism for the inhibition of 5-lipoxygenase by this class of inhibitors was proposed. PMID- 1903451 TI - Effectiveness of carbaryl applications for the control of Ixodes dammini (Acari: Ixodidae) nymphs in an endemic residential area. AB - Ground applications of carbaryl in early June 1989 reduced populations of nymphal Ixodes dammini Spielman, Clifford, Piesman & Corwin by 100% in five 0.4-ha residential sites 72 h after application. High levels of control (greater than 90%) persisted for almost 2 mo. Five nymphs were recovered at the periphery of the sprayed plots at two sites 2 wk after spraying and nine nymphs were collected at the periphery of the sprayed plots at three of the sites 4-5 wk after application. At 8 wk after application, I. dammini nymphs were recovered within three of the sprayed plots. Chemical control of nymphal I. dammini may be a viable management practice for homeowners living in endemic areas to reduce the chances of acquiring Lyme disease. PMID- 1903452 TI - Field evaluation of carbon dioxide baits for sampling Ornithodoros turicata (Acari: Argasidae) in gopher tortoise burrows. AB - Field studies were conducted to assess the reliability of carbon dioxide baits in sampling Ornithodoros turicata Duges. Tick response to about 50 g of dry ice placed at various distances away from tick-infested burrows was monitored over a 2-h period. In addition, tick attraction to different flow rates of carbon dioxide was monitored. Tests were conducted over a 15-mo period, during which seasonal effects on O. turicata response to CO2 were assessed. The efficacy of the baits was evaluated at night and in daytime. Ticks responded to dry ice baits placed up to 8 m away from the burrows. There was no significant difference in the total number of ticks attracted in a 1-h period using 500 to 2,000 ml CO2/min. At night, ticks were attracted to CO2 bits throughout the year except in December and January. By contrast, ticks were attracted to CO2 baits during daytime only between May and mid-December. PMID- 1903453 TI - Consumption of fish: benefits and perceived risk. AB - Fish, a useful source of protein, may be polluted by microbes, natural toxins, and/or synthetic chemicals. However, based on a review of the U.S. General Accounting Office, "There does not appear to be a compelling case to implement a mandatory comprehensive federal seafood inspection program." Although earlier studies showed higher body burdens of polychlorinated biphenyls (PCBs) in populations who consumed a lot of fish from polluted waterways, a recent study refutes these observations. No information is available in the United States on the levels of polychlorinated dibenzodioxins (PCDDs) and dibenzofurans (PCDFs) in anglers who consume a great deal of fish presumed to be contaminated by these chemicals. PMID- 1903454 TI - Role of FDA in establishing tolerable levels for dioxin and PCBs in aquatic organisms. AB - When fishery products shipped in interstate commerce contain an environmental contaminant that presents a potential threat to public health, the Food and Drug Administration (FDA) undertakes appropriate regulatory steps to minimize exposure. These efforts range from seizure of the affected product to formal rule making to establish a limit. The basic provision of the Food, Drug, and Cosmetic (FD&C) Act by which the agency deals with environmental contaminants in the food supply is section 402(a)(1), which deals with poisonous and deleterious substances. Poisonous and deleterious components are deemed to be "added," even if they are natural constituents of food, if any amount is present through the artifice of man. Furthermore, when the level of a naturally occurring toxin is increased in the food through handling and/or processing, the sum of all of the contaminant is deemed to be "added." Unavoidable environmental contaminants may be controlled and/or regulated under this section by the "may render injurious" standard, whereby the agency must demonstrate that there is a significant possibility that exposure to the contaminant could be injurious to human health. "Action levels" are administrative guidelines or instructions to the agency field units that define the extent of contamination at which the agency may regard food as adulterated. Except for polychlorinated biphenyls, for which there is a tolerance established by regulation, FDA has controlled contaminants in aquatic organisms by using action levels. Under section 406 of the FD&C act, the agency can also establish tolerances for unavoidably added poisonous or deleterious substances. This section allows the agency to consider the extent to which a contaminant is unavoidable in food while it limits exposure to the extent necessary to protect the public health. Section 406 requires that the tolerance be established by assessing several factors, including risk. One of these is the capability of processing technology to prevent, reduce, or otherwise control the level of the contaminant. Another factor is the necessity to avoid the needless removal of large amounts of valuable food from the market. Finally, the available analytical and sampling methods must be capable of measuring the contaminant so as to ensure the enforceability of the tolerance. Although the FDA has no statutory authority over intrastate fishing considerations, such as noncommercial fishing, it does provide advice to local or state authorities. It is the best scientific opinion the agency can give, but it is not enforceable per se. Advice is provided when requested by local and state officials where no guideline or tolerance is available, and is meant to deal with local and/or regional public health concerns.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1903455 TI - Differential neuronal expression of c-fos proto-oncogene following peripheral nerve injury or chemically-induced seizure. AB - Previous work by others has demonstrated that neocortical injury results in the induction of c-fos protooncogene both at and distal to the site of injury. However, secondary effects of focal brain injury, such as spreading depression and seizure activity, also have been shown to induce the expression of c-fos. Thus, it is unclear whether the stimulus inducing c-fos expression after generalized brain trauma is direct neuronal injury or associated, secondary effects of injury. In this study, we tested the hypothesis that a specific axonal disconnection would induce the expression of c-fos proto-oncogene in the injured neurons. The injury paradigm that was used was peripheral axotomy of rodent facial motoneurons. The right facial nerve was severed distal to the stylomastoid foramen, with the left side serving as an internal control. As positive controls, in a separate group of animals, seizures were invoked using bicuculline administered intraperitoneally. At the end of postoperative survival times ranging from 30 min to 24 hr, the animals were sacrificed. For northern blot analysis using a c-fos cDNA probe, total RNA was isolated from the dissected facial nuclear groups in the injury experiments, or whole brain and neocortex in the seizure experiments. For immunocytochemical analysis using a battery of c-fos antibodies, the animals were perfused with paraformaldehyde and processed for routine light microscope immunocytochemistry. In the bicuculline-injected animals, c-fos mRNA was massively induced in whole brain in a manner proportional to the overall level of gross seizure activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1903457 TI - Postoperative artificial nutrition support of the urological patient. PMID- 1903456 TI - vRel is an inactive member of the Rel family of transcriptional activating proteins. AB - The vRel oncoprotein is member of a family of related proteins that also includes cRel, NF-kappa B, and Dorsal. We investigated the transcriptional regulatory properties of several Rel proteins in cotransfection assays with chicken embryo fibroblasts (CEF). Retroviral vectors expressing hybrid proteins that contain the DNA-binding domain of LexA fused to portions of the viral oncoprotein vRel or chicken, mouse, human, or Drosophila melanogaster (Dorsal) cRel proteins were cotransfected with a reporter plasmid that contains the DNA sequence recognized by LexA, a promoter, and the assayable gene for chloramphenicol acetyltransferase. In transient assays, a LexA-vRel protein did not activate transcription in CEF. Full-length chicken cRel, mouse cRel, and Dorsal fusion proteins all activated transcription weakly; however, deletion of N-terminal Rel sequences from each of these proto-oncogene encoded proteins resulted in strong activation by LexA fusion proteins containing only C-terminal sequences. Inhibition of the C-terminal chicken cRel gene activation domain by N-terminal sequences was seen in CEF and mouse and monkey fibroblasts. These results show that cRel proteins from different species have the same general organization: an N-terminal inhibitory domain and a C-terminal activation domain. Sequence comparison suggests that the inhibitory domain is conserved but the activation domain is species specific. In contrast, vRel lacks a strong C-terminal gene activation function, since a LexA fusion protein containing C-terminal vRel sequences alone only weakly activated transcription. In addition, the wild-type vRel protein (lacking LexA sequences) repressed transcription from reporter plasmids containing NF-kappa B target sequences; nontransforming vRel mutants did not repress transcription from these plasmids. Our results suggest that vRel transforms cells by interfering with transcriptional activation by cellular Rel proteins. PMID- 1903458 TI - Re: Bladder wall calcification after intravesical mitomycin C treatment of superficial bladder cancer. PMID- 1903460 TI - Etidronate and osteoarthritis. PMID- 1903459 TI - The inhibition of metabolic oxalate production by sulfhydryl compounds. AB - A number of sulfhydryl compounds were shown to inhibit CO2 and oxalate formation from glyoxylate by rat liver homogenates and hepatocytes. The most significant inhibition occurred with cysteine and this inhibition was concentration dependent. In rats made hyperoxaluric by administering ethylene glycol in their drinking water, daily intraperitoneal injections of cysteine caused a rapid and marked decrease in urinary oxalate excretion which was maintained over the duration of the treatment (28 days). Over this time period, the level of urinary oxalate excretion in these ethylene glycol-treated rats was reduced to that of the controls. It is postulated that the decrease is due to the formation of a cysteine-glyoxylate adduct, 2-carboxy-4-thiazolidine carboxylate, which prevents glyoxylate being further oxidized to oxalate. Cysteine or similar sulphydryl compounds may therefore have potential as therapeutic agents in the prevention of renal stones. PMID- 1903461 TI - From the Food and Drug Administration. PMID- 1903462 TI - Hepatitis C in HIV-infected intravenous drug users and homosexual men in suburban New York City. PMID- 1903463 TI - [Diabetic microangiopathy--pathogenesis]. PMID- 1903464 TI - [Diabetic ketoacidotic coma]. PMID- 1903465 TI - [Insulin deprived NIDDM--analysis of NIDDM with abrupt onset and ketosis]. PMID- 1903466 TI - [Surgical and anesthetic management of diabetic patients]. PMID- 1903467 TI - [Hemopurification in the management of ARDS complicating multiple organ failure]. AB - In the field of critical care medicine, it has been claimed that ARDS often develops as a part of multiple organ failure (MOF). Since multi-modality therapy is necessary in the management of MOF, it is also mandatory even in the management of ARDS. Among the various therapeutic approaches for patients with MOF, hemopurification is one of the most effective therapeutic tools. Various hemopurification methods such as hemodialysis, peritoneal dialysis, hemoadsorption, hemofiltration and plasma exchange have been applied in the management of MOR. However, our recent experiences suggest that continuous hemofiltration (CHF) and/or continuous hemodiafiltration (CHDF) are safest, most easily performed and effective hemopurification in the management of ARDS/MOF. The efficacy of hemopurification in the management of ARDS is summarized as follows. 1) Removal of humoral mediators and causative substances of ARDS following insults such as sepsis and trauma. 2) Treatment of pulmonary interstitial permeability edema which has been claimed to be one of the most important pathological conditions in ARDS. 3) Removal of excess water given as carrier in IVH solution and accumulating in the body. 4) Immunomodulation which has also been considered to be necessary in the treatment or prevention of ARDS. PMID- 1903470 TI - [Stress in the work place. Conditions for effective occupational stress prevention]. PMID- 1903469 TI - [Experiences with capnometry in pediatric intensive care]. AB - We investigated the correlation between arterial and end-tidal pCO2 in 17 children during intensive care. The indications for using capnometry were noninvasive monitoring of ventilation after cardiac surgery or during complicated course of illness or for control of intended hyperventilation. We found a good correlation between arterial and end-tidal pCO2 in the overall patient population (r = 0.82), but the relationship varied widely from patient to patient. There was only a weak correlation (r = 0.44) in pCO2 over 45 mm Hg. Hyperventilation could be identified in 64.2%, whereas hypoventilation was correctly indicated in only 23%. PMID- 1903468 TI - [Reference values for blood levels of free thyroxine, free triiodothyronine and thyroxine-binding globulins in euthyroid children. Method: luminescence-enhanced enzyme immunoassay]. AB - Concentrations of free thyroxine (n = 296, male 164, female = 132), free triiodothyronine (n = 273, male 156, female = 117) and thyroxine-binding globulin (n = 273, male 156, female = 117) were determined using the luminescence enhanced enzyme immunoassay method in blood-serum of euthyroid children. Beyond the 30, day of life no significant differences were found in different age groups for the free thyroxine and beyond the 2, day of life for the free triiodothyronine concentration. The free thyroxine values of the infants in the range of 15-39 pg/ml decreased to the range of 9-18.5 pg/ml and the free triiodothyronine values decreased from 3.4-9.3 pg/ml to the range of 2.8-6.5 pg/ml. The values for thyroxine-binding globulin increased in the first month of life up to the range of 18-35 mg/l and decreased afterwards continuously to the range of 14.5-26.5 mg/l. PMID- 1903471 TI - [Possibilities of cancer prevention. Results of psychoneuroimmunology]. PMID- 1903472 TI - [Concepts on dealing with risks in gene technics]. PMID- 1903473 TI - [Cooperation between hospital and social work department]. PMID- 1903474 TI - [Diploma program nursing education at the Humboldt University in Berlin]. PMID- 1903475 TI - [Incontinence and toilet training]. PMID- 1903476 TI - [Living with incontinence. Report by a patient]. PMID- 1903477 TI - [On the death of Bertha and Karel Bobath]. PMID- 1903478 TI - [A school for patients in long-term hospital care in Ulm]. PMID- 1903479 TI - Expression of leukemia inhibitory factor is regulated in human mesenchymal cells. AB - A protein variously termed leukemia inhibitory factor (LIF), differentiation inducing factor, differentiation inhibitory activity or human interleukin for DA cells can control the differentiation and proliferation of hematopoietic cells as well as of several other cellular lineages. In order to further elucidate the spectrum of LIF-producing cells, we examined different cell types for the expression of LIF mRNA using Northern blot analysis. LIF mRNA was detected in activated normal human T-cells and in two T-cell lines but was undetectable in a B-lymphoid cell line, in both resting and activated normal human granulocytes and monocytes and in human myeloid cell lines K562 and HL-60. In human lung fibroblasts and in human umbilical vein endothelial cells, LIF was constitutively expressed and its accumulation was increased in a time-dependent manner following treatment with the phorbol ester TPA and in the presence of the two immediate response cytokines tumor necrosis factor (TNF)-alpha and interleukin (IL)-1-beta. We conclude that mRNA for LIF is not only expressed by T-cells but also in human mesenchymal cells. Expression of LIF transcripts in these cells is constitutive and can be significantly enhanced by phorbol ester, TNF-alpha and IL-1-beta. PMID- 1903481 TI - Molecular mechanism of tyrosinase regulation by L-dopa in hamster melanoma cells. AB - Exposure of hamster amelanotic melanoma cells to L-dihydroxyphenylalanine (L DOPA) resulted in a time dependent increase of cell pigmentation, tyrosinase concentration and activity with peak after 24 hours. Northern blot analysis showed a small but reproducible increase of tyrosinase mRNA after 3 hours and a decrease below the control level after 9 hours. After 24 and 48 hours tyrosinase mRNA was undetectable. It is suggested that L-DOPA or its oxidation products can stimulate intracellular tyrosinase concentration and regulate tyrosinase mRNA level both in positive and negative fashion. PMID- 1903480 TI - Establishment and characterization of a murine megakaryoblastic cell line growing in protein-free culture (L8057Y5). AB - A murine megakaryoblastic cell line growing in protein-free culture (L8057Y5) was established from an experimentally induced murine leukemia (MK8057). Most of the Y5 cells were small and blast-like, with 2-4N in DNA content. Also, large cells possessing a lobulated nucleus characteristic of megakaryocytes, which showed polyploidization to more than 4N up to 16N, were occasionally seen. Nearly 5% of the total number of Y5 cells were positive for acetylcholinesterase reaction. The survival time of C3H/He mice after injection with Y5 cells was longer than that of mice injected with the original MK8057 cells. The colony-forming ability of Y5 cells in the spleen of the lethally irradiated mouse was much lower, whereas the number of in vitro colonies derived from Y5 was greater than that of MK8057. The plating efficiency of colony formation in serum-free methylcellulose culture was higher at a low O2 tension. Conditioned medium of Y5 cells enhanced colony formation as well as 3H-TdR uptake by Y5 cells, which implies that Y5 cells may produce autocrine growth factor(s). mRNAs for IL-6, LIF, and INF-gamma were expressed in Y5 cells; these cytokines may have roles in the growth mechanisms of the cell line. PMID- 1903482 TI - Controlled ventilation during NMR spectroscopic studies: hemodynamic and biochemical consequences. AB - The effects of different ventilation methods on cardiac output measured by the indicator-dilution method, liver blood flow measured by a deuterium washout technique using 2H nuclear magnetic resonance (NMR) and liver concentrations of ATP and intracellular pH determined with 31P NMR were compared in anesthetized rats. No differences in mean arterial blood pressure were demonstrable with the different modes of ventilation. However, significant drops in cardiac output were observed between freely breathing and animals ventilated with positive pressure but not the high frequency oscillatory method (407 +/- 46 and 520 +/- 88 vs. 633 +/- 86 ml/min/kg, p less than 0.05 and p = NS, respectively). Moreover, liver blood flow was significantly reduced during positive pressure but not high frequency oscillatory ventilation compared with free breathing rats (32 +/- 4 and 43 +/- 10 vs. 46 +/- 8 ml/100 g, p less than 0.05 and p = NS, respectively). 31P NMR spectroscopy revealed no effects of either ventilation method on tissue ATP or intracellular pH as estimated by the chemical shift of inorganic phosphate. These data suggest that controlled ventilation in normal rats accomplished with standard positive pressure methods is associated with major decreases in cardiac output and liver blood flow despite maintenance of normal blood pressure. High frequency oscillatory ventilation appears to effect less compromise of cardiac output and hepatic perfusion than positive pressure ventilation and may, therefore, be preferable for some biological studies. PMID- 1903483 TI - Purification and characterization of adenylyl cyclase from Bacillus anthracis. PMID- 1903484 TI - Preparation and application of GTP-agarose matrices. PMID- 1903485 TI - Preparation of guanine nucleotide-free G proteins. PMID- 1903486 TI - Purification of recombinant Gs alpha. PMID- 1903487 TI - Purification of recombinant Gi alpha and Go alpha proteins from Escherichia coli. PMID- 1903488 TI - Synthetic peptide antisera with determined specificity for G protein alpha or beta subunits. PMID- 1903489 TI - Quantitation and purification of ADP-ribosylation factor. PMID- 1903490 TI - ADP-ribosylation of G proteins with pertussis toxin. PMID- 1903491 TI - Cholera toxin-catalyzed [32P]ADP-ribosylation of proteins. PMID- 1903492 TI - Photoaffinity labeling of GTP-binding proteins. PMID- 1903493 TI - Quantitative immunoblotting of G-protein subunits. PMID- 1903495 TI - Tryptophan fluorescence of G proteins: analysis of guanine nucleotide binding and hydrolysis. PMID- 1903494 TI - Assay of G-protein beta gamma-subunit complex by catalytic support of ADP ribosylation of Go alpha. PMID- 1903496 TI - Purification of tubulin and tau from chicken erythrocytes: tubulin isotypes and mechanisms of microtubule assembly. PMID- 1903498 TI - [Successful treatment of massive hemorrhagic diathesis caused by Factor VIII:C antibodies with adsorption plasmapheresis and immunosuppression]. PMID- 1903497 TI - [Pravastatin, cholestyramine and gemfibrozil in long-term therapy of primary hypercholesterolemia. An open randomized comparative study]. AB - In this open controlled clinical trial the lipid-lowering effect, the tolerance and clinical safety of the new hydrophilic HMG-CoA reductase inhibitor pravastatin and cholestyramine were compared in the treatment of 45 patients with primary hypercholesterolaemia over a period of 16 weeks. Following a dietary lead in of six weeks, patients were randomized at a ratio of 3:2 to receive either pravastatin 10 mg b.i.d. or cholestyramine 8 g b.i.d. The dose of pravastatin was increased to 40 mg per day after eight weeks of treatment and after 16 weeks cholestyramine 8 g b.i.d. was added. Two thirds of the patients in the cholestyramine group were switched to gemfibrocil 900 mg. At the end of the 48 week treatment period the mean reduction rates of total cholesterol, LDL cholesterol and triglycerides for the pravastatin combination compared to cholestyramine (in brackets values for gemfibrocil) were -30, -35 and -17% versus -17 (-19), -25 (-22) and +27 (-24)%. Pravastatin lead to an increase of the HDL concentration of approximately 8%, gemfibrocil to approximately 13%, whilst cholestyramine alone did not change this lipid fraction. The reduction of total cholesterol and LDL-cholesterol was associated with a decrease in the apolipoprotein B concentration. However, the apolipoprotein AI and AII levels remained unchanged. Due to the absence of clinically relevant side effects and laboratory abnormalities coupled with the excellent compliance in this study, pravastatin proved to be a convincing therapeutic alternative to cholestyramine and gemfibrocil. The combination therapy of pravastatin and cholestyramine offers a potentially highly efficacious and safe therapeutic regimen for the future. PMID- 1903499 TI - [Seckel's syndrome]. AB - The case of a girl with Seckel syndrome, born of an epileptic mother who was taking anticonvulsant drugs, is reported. The patient, admitted to our clinic for short stature, presented some signs of Seckel syndrome: microcephaly, a "bird headed" profile with receding chin and forehead and large beaked nose. Microcephaly and a low birth weight are present in Seckel syndrome, but also in the newborn of epileptic mothers who received anticonvulsive drugs. In the present paper the Authors questioned if the described syndrome was caused by the use of antiepileptic drugs during pregnancy, or epilepsy of the mother, or if it was casual. PMID- 1903500 TI - Deletion of the psbG1 gene of the cyanobacterium Synechocystis sp. PCC6803 leads to the activation of the cryptic psbG2 gene. AB - The genes psbG1 and psbG2 in the cyanobacterium Synechocystis sp. PCC6803 are homologous. The psbG1 gene is located on the chromosome and is part of the ndhC- psbG1--ORF157 operon, while psbG2 is located on a plasmid and is not flanked by equivalent ndhC or ORF157 genes. Mutants in which psbG1 is deleted grow well under autotrophic conditions, while their growth is impeded in mixotrophic medium. These results argue against a functional role for psbG1 in photosynthesis, i.e. photosystem II, and are more compatible with a function in respiration. The psbG2 gene is not transcribed in wild-type cells, but in psbG1 mutants the insertion of DNA sequences in close proximity to the psbG2 reading frame has led to transcriptional activation of psbG2. Thus, psbG2 represents an example of a cryptic gene, similar to those found in other bacteria. PMID- 1903501 TI - Transient expression of foreign DNA during embryonic and larval development of the medaka fish (Oryzias latipes). AB - Species of small fish are becoming useful tools for studies on vertebrate development. We have investigated the developing embryo of the Japanese medaka for its application as a transient expression system for the in vivo analysis of gene regulation and function. The temporal and spatial expression patterns of bacterial chloramphenicol acetyltransferase and galactosidase reporter genes injected in supercoiled plasmid form into the cytoplasm of one cell of the two cell stage embryo was promoter-specific. The transient expression was found to be mosaic within the tissue and organs reflecting the unequal distribution of extrachromosomal foreign DNA and the intensive cell mixing movements that occur in fish embryogenesis. The expression data are consistent with data on DNA fate. Foreign DNA persisted during embryogenesis and was still detectable in some 3- and 9-month-old adult fish; it was found in high molecular weight form as well as in circular plasmid conformations. The DNA was replicated during early and late embryogenesis. Our data indicate that the developing medaka embryo is a powerful in vivo assay system for studies of gene regulation and function. PMID- 1903503 TI - Molecular cloning and analysis of the chromosomal region 26A of Drosophila melanogaster. AB - Region 26A of the second chromosome of Drosophila melanogaster has been extensively characterized at the genetic level. We report here the cloning of virtually the entire 26A region via a bidirectional chromosome walk. Deletion and translocation breakpoints in the 26A interval have been localized at the molecular level by both chromosomal in situ hybridization and Southern analysis. The locations of the genetically defined loci in this chromosomal region have also been correlated with transcriptional units mapped onto the DNA of the proximal region of the chromosomal walk. The position of the alpha glycerophosphate dehydrogenase (alpha-Gpdh) gene in 26A5-7 has been confirmed and a putative transcriptional unit for the beta-galactosidase-1 (beta-Gal-1) gene has been identified in the 26A7-9 interval. PMID- 1903502 TI - The synthesis of the two S-adenosyl-methionine synthetases is differently regulated in Saccharomyces cerevisiae. AB - S-adenosyl-L-methionine (AdoMet) is synthesized by transfer of the adenosyl moiety of ATP to the sulfur atom of methionine. This reaction is catalysed by AdoMet synthetase. In all eukaryotic organisms studied so far, multiple forms of AdoMet synthetases have been reported and from their recent study, it appears that AdoMet synthetase is an exceptionally well conserved enzyme through evolution. In Saccharomyces cerevisiae, we have demonstrated the existence of two AdoMet synthetases encoded by genes SAM1 and SAM2. Yeast, which is able to concentrate exogenously added AdoMet, is thus a particularly useful biological system to understand the role and the physiological significance of the preservation of two almost identical AdoMet synthetases. The analysis of the expression of the two SAM genes in different genetic backgrounds during growth under different conditions shows that the expression of SAM1 and SAM2 is regulated differently. The regulation of SAM1 expression is identical to that of other genes implicated in AdoMet metabolism, whereas SAM2 shows a specific pattern of regulation. A careful analysis of the expression of the two genes and of the variations in the methionine and AdoMet intracellular pools during the growth of different strains lead us to postulate the existence of two different AdoMet pools, each one supplied by a different AdoMet synthetase but in equilibrium with each other. This could be a means of storing AdoMet whenever this metabolite is overproduced, thus avoiding the degradation of a metabolite the synthesis of which is energetically expensive. PMID- 1903504 TI - The faint band/interband region 28C2 to 28C4-5(-) of the Drosophila melanogaster salivary gland polytene chromosomes is rich in transcripts. AB - Urate oxidase mRNA and five other transcripts map along 38 kb of DNA in the region 28C on the Drosophila melanogaster second chromosome. Three biotinylated restriction fragments from this 38 kb of DNA, one from each end and one from the middle, were individually hybridized in situ to slightly stretched salivary gland polytene chromosomes. The data from these in situ hybridizations in combination with the transcription map of the 38 kb of DNA indicate that: (i) there are six discrete RNA species encoded along the 38 kb of DNA and (ii) these six transcripts map to the faint band/interband region which includes the proximal edge of 28C1, the three faint bands, 28C2, 28C3 and 28C4-5(-), and the adjacent interband chromatin. Our data are consistent with the few published studies directly demonstrating that faint band/interband regions of the Drosophila melanogaster salivary gland polytene chromosomes code for a high density of transcripts. PMID- 1903506 TI - The relationship between induced reciprocal translocations and cell killing of rhesus monkey spermatogonial stem cells after combined treatments with follicle stimulating hormone and X-rays. AB - The induction of reciprocal translocations in spermatogonial stem cells of monkeys (rhesus and crab-eating), visualized in dividing primary spermatocytes, was studied after combined treatments with follicle-stimulating hormone (FSH, 54 IU/kg/week) and X-rays (1 Gy). No clear differences in the frequencies of induced translocations between FSH-pretreated and non-pretreated animals were recorded. Comparison of these translocation data with studies on cell killing in the same monkeys shows that the ratio between the probabilities that radiation-induced basic lesions kill a cell or produce translocations (the p/c ratio) is of the same order of magnitude as that observed for the mouse. Consequently the well documented differences in radiation response between the rhesus monkey and the mouse cannot be explained by differences in the p/c ratio. It is concluded that differences in multiplication-differentiation patterns of surviving stem-cell spermatogonia after irradiation are probably responsible for the observed differences between mice and rhesus monkeys. PMID- 1903505 TI - Plasmid deletion formation between short direct repeats in Bacillus subtilis is stimulated by single-stranded rolling-circle replication intermediates. AB - The effects of the rolling-circle mode of replication and the generation of single-stranded DNA (ss DNA) on plasmid deletion formation between short direct repeats in Bacillus subtilis were studied. Deletion units consisting of direct repeats (9, 18, or 27 bp) that do or do not flank inverted repeats (300 bp) were introduced into various plasmid replicons that generate different amounts of ss DNA (from 0% to 40% of the total plasmid DNA). With ss DNA-generating rolling circle-type plasmids, deletion frequencies between the direct repeats were 3- to 13-fold higher than in plasmids not generating ss DNA. When the direct repeats flanked inverted repeats the deletion frequencies in ss DNA-generating plasmids were increased by as much as 20- to 140-fold. These results support models for deletion formation based on template-switching errors during complementary strand synthesis of rolling-circle-type plasmids. The structural instability (deletion formation between short direct repeats) of the ss DNA-generating plasmid pTA1060 in B. subtilis was very low in the presence of a functional initiation site for complementary strand synthesis (minus origin). This observation suggests that it will be possible to develop stable host-vector cloning systems for B. subtilis. PMID- 1903508 TI - Genotoxicity testing with the somatic white-ivory system in the eye of Drosophila melanogaster. AB - The white-ivory test in Drosophila melanogaster is designed to detect chemically induced reversions of the sex-linked, recessive unstable eye-color mutation white ivory to the wild-type form. After exposure of larvae reversions are detectable as clones of red facets in the eye of newly enclosed adult flies. Tester strains containing a quadruplication of the white-ivory gene on the X-chromosome(s) were used. In a strain with males carrying 4 copies of the gene and females carrying 8 copies of the gene, spontaneous reversions occurred proportional to the gene copy number. In contrast to this, chemically induced reversions occurred only 1.36 times more frequently in females (carrying 8 copies of the gene) than in males (carrying 4 copies). Since chemicals inducing different lesions in DNA (bleomycin, cyclophosphamide, daunomycin, diethyl sulfate and 7,12 dimethylbenz[a]anthracene) did induce statistically significant frequencies of reversions the test appears to be capable of detecting a wide variety of genotoxic chemicals with different modes of action. The recombinogen strychnine did not induce reversions. PMID- 1903507 TI - Effect of estrogen on induction of micronuclei by mutagens in male mice. AB - The effect of estrogen on the induction of micronucleated polychromatic erythrocytes (MPCE) by mutagens was examined in male mice. In the dose-response study, a dose-related inhibition of the mitomycin C (MMC)-induced MPCE frequency by estradiol (E2) treatment was observed. In the time study, inhibitory effects of E2 on MPCE frequency by MMC were observed when MMC was administered at 0 or 1 day after injection of E2. The most effective protocol for inhibition was when E2 and MMC were used on the same day. Of mutagens other than MMC, only vincristine (VCR) showed a significant decrease in MPCE frequency when used together with E2. Benzo[a]pyrene (BaP) and 5-fluorouracil (5-FU) showed no significant decrease in MPCE frequency. The data suggest that the induction of micronuclei by mutagens is inhibited by treatment with estrogen, and this could result in a sex difference in the sensitivity of mice employed in the micronucleus test. Mechanisms of the inhibitory effects of estrogen are discussed; these might include a suppression of erythropoiesis and a possible effect on the cell membrane permeability of erythroblasts. PMID- 1903509 TI - Germany's health care system (2). PMID- 1903510 TI - Effects of base-soluble proteins and methanol-soluble polysaccharides from corn on mycelial growth of Aspergillus flavus. AB - The antifungal activity of base-soluble proteins (BSP) and methanol-soluble polysaccharides (PS) from A. flavus resistant (Yellow Creole) and susceptible (Huffman) genotypes of corn were investigated by in vitro studies. Bioassays of fungal growth inhibition in agar media showed antifungal activity by proteins and polysaccharides only from the Huffman genotype. Microgramme quantities of protein and polysaccharides were required to retard fungal growth. The polysaccharides have molecular weights greater than 3.5 kilodaltons. Cathodic PAGE of native protein from the two genotypes showed six protein bands with differences in staining intensity of individual components. SDS-PAGE showed four distinct bands in Yellow Creole that were absent in Huffman. Both of the protein samples contained traces of carbohydrate. Analysis of hydrolyzed polysaccharide from the two genotypes showed different proportions of mannose and glucose. PMID- 1903511 TI - Decrease of aflatoxin B1 in yoghurt and acidified milks. AB - Fermentation of yoghurt and acidified milks containing aflatoxin B1 (AB1) were studied. AB1 added to milk before fermentation at concentrations of 600, 1000 and 1400 micrograms/kg was reduced in yoghurts (pH 4.0) by 97, 91 and 90%, respectively. Coagulation time was approximately the same as in the controls. Streptococci had longer chains than those in the controls. The main decrease of AB1 occurred during the milk fermentation. A decrease of AB1 (conc. 1000 micrograms/kg) in milks acidified with citric, lactic and acetic acids (pH 4.0) was 90, 84 and 73%, respectively. PMID- 1903512 TI - Different media and methodologies for the detection of aflatoxin production by Aspergillus flavus strains isolated from trout feed. AB - We have studied the aflatoxin producing capacity of 41 Aspergillus flavus strains isolated from the mycoflora present of natural media (wheat, rice and mixed feed) synthetic medium (Aflatoxin Producing Ability Medium) and semisynthetic media (Coconut Agar Medium and Glucose Yeast Extract Agar) were compared. Aflatoxins were analysed on days 4 and 8 post-inoculation under an incubation temperature of 28 degrees C. A total of 30 strains (75.7%) were producers on natural media as detected by Thin Layer Chromatography: 23 strains on wheat, 27 on rice and 12 on mixed feed. The results by qualitative fluorescence tests on synthetic and semisynthetic media were: 3 strains positive on Coconut Agar Medium (CAM) 1 on Glucose Yeast Extract Agar (GY + Agar) and none on Aflatoxin Producing Ability Medium (APA). PMID- 1903514 TI - Olfaction. The strong scent of success. PMID- 1903515 TI - Animal experimentation. NIH lose a legal shield. PMID- 1903513 TI - Phagocyte-mediated killing of Candida tropicalis. AB - Human peripheral monocytes (MO), neutrophils (PMN), and lymphocytes (PBL) were tested for their ability to kill Candida tropicalis. With incubation times between 30 min and 2 h, unstimulated MO and PMN, but not PBL, were efficient killers of C. tropicalis. Both leukocyte subsets were able to kill at minimum 2.5:1 effector to target ratios. Pre-incubation of MO for 24 h with interferon gamma or tumor necrosis factor (TNF) increased their ability to kill yeast targets. TNF alone had no effect on C. tropicalis targets at concentrations up to 1000 U/ml. PBL activated for 4 d with interleukin-2 did not kill yeast targets. PMN exhibited more cytocidal efficiency per cell than MO in these assays. Direct contact of effectors and targets was required; no significant killing by PMN or MO supernatants was measured. PMN-mediated killing, but not MO killing, was inhibited by a mixture of catalase and superoxide dismutase suggesting that oxygen-dependent killing mechanisms were partially responsible for candidacidal activity. PMID- 1903516 TI - Bcr encodes a GTPase-activating protein for p21rac. AB - More than thirty small guanine nucleotide-binding proteins related to the ras encoded oncoprotein, termed Ras or p21ras, are known. They regulate many fundamental processes in all eukaryotic cells, such as growth, vesicle traffic and cytoskeletal organization. GTPase-activating proteins (GAPs) accelerate the intrinsic rate of GTP hydrolysis of Ras-related proteins, leading to down regulation of the active GTP-bound form. For p21ras, two GAP proteins are known, rasGAP and the neurofibromatosis (NF1) gene product. There is evidence that rasGAP may also be a target protein for regulation by Ras and be involved in downstream signalling. We have purified a GAP protein for p21rho, which is involved in the regulation of the actin cytoskeleton. Partial sequencing of rhoGAP reveals significant homology with the product of the bcr (breakpoint cluster region) gene, the translocation breakpoint in Philadelphia chromosome positive chronic myeloid leukaemias. We show here that the carboxy-terminal domains of the bcr-encoded protein (Bcr) and of a Bcr-related protein, n chimaerin, are both GAP proteins for the Ras-related GTP-binding protein, p21rac. This result suggest that Bcr could be a target for regulation by Rac and has important new implications for the role of bcr translocations in leukaemia. PMID- 1903518 TI - Nursing home resident assessment classification and focused care. AB - Boondas provides the reader with an interesting history of the development of nursing homes as a prelude to discussion of reimbursement issues and case mix classification for today's residents. The need for minimal data sets and patient classification systems is stressed. PMID- 1903517 TI - [Transplantation of dopamine producing nerve cells: a new therapy in idiopathic Parkinson syndrome?]. PMID- 1903519 TI - Annual meeting of the American Academy of Otolaryngology--Head and Neck Surgery Foundation, Inc., Kansas City, Missouri, September 22-26, 1991. 1991 instruction course program. PMID- 1903520 TI - Physician advisors make final decisions. PMID- 1903521 TI - Origin of intact lactoferrin and its DNA-binding fragments found in the urine of human milk-fed preterm infants. Evaluation by stable isotopic enrichment. AB - The origin of intact (78-kD) lactoferrin found in the urine of human milk-fed preterm infants was investigated using human milk containing proteins enriched with [13C]leucine and [15N2]lysine or [2H4]lysine. Mothers of infants selected for the study were infused i.v. with [13C] leucine and [15N2]lysine or [2H4]lysine to label milk proteins. The labeled milk was collected from each mother, pooled, fortified with a lyophilized human milk fraction, and fed to her preterm infant by continuous orogastric infusion for a period of 48 h. Urine was collected from each infant for 96 h. Intact lactoferrin (78 kD) and DNA-binding lactoferrin fragments (51 and 39 kD) were purified from the urine by affinity chromatography on columns of immobilized single-stranded DNA-agarose. The concentration and isotopic enrichment of the intact lactoferrin and DNA-binding fragments were determined separately after their isolation by high-performance reverse-phase (phenyl) chromatography. Mass spectral analyses indicated that the isotopic enrichment of the purified urinary lactoferrin was 87 to 100% of that in the labeled human milk lactoferrin. Similar results were obtained for the isolated DNA-binding lactoferrin fragments. The ratios of isotopically labeled leucine to lysine in the purified milk lactoferrins and urinary lactoferrins were similar for each mother/infant pair. Isotopically labeled lysine, added to the milk as free amino acid, was not incorporated into the purified urinary lactoferrin. These results demonstrate that undegraded (78-kD) lactoferrin of maternal origin is absorbed by the gut and excreted intact in the urine of preterm infants; nearly all of the urinary lactoferrin was of maternal origin. The possible immunoregulatory functions of the absorbed intact, maternal lactoferrin are discussed. PMID- 1903523 TI - Abnormal signal transduction in a patient with severe combined immunodeficiency disease. AB - We have studied an 8-yr-old male patient with adenosine deaminase-positive severe combined immunodeficiency disease with a normal number of peripheral CD3+, T cell receptor-alpha beta+ T cells. The majority of these T cells expressed the CD8 molecule and were oligoclonal in nature as proven by Southern blot analysis of the T cell receptor genes. T cells failed to proliferate in vitro either upon stimulation with T cell mitogens or when stimulated with a combination of the phorbol ester phorbol myristate acetate and the Ca-ionophore ionomycin. High doses of recombinant IL-2, when added to in vitro cultures, were able to restore proliferation induced by phorbol myristate acetate and ionomycin but the response to concanavalin A remained severely defective. However, activation of the patient's T cells with phytohemagglutinin or concanavalin A induced an increase of free cytoplasmic Ca++, which was 2- to 5-fold higher than in normal CD8+ T cells. Furthermore, phorbol myristate acetate or phytohemagglutinin induced the translocation of protein kinase C from cytosol to plasma membrane. Analysis of membrane phospholipid composition of the patient's T cells disclosed that the ratio of phosphatidylcholine to phosphatidylserine was 5-fold higher than in normal T cells. The abnormal Ca++ response after activation with T cell mitogens as well as the high phosphatidylcholine/phosphatidylserine ratio may be causally linked to the defective in vitro T cell proliferation. Because the capacity of T lymphocytes to produce or respond to IL-2 may vary, the oligoclonality of the T cells of the patient should be considered as well in the explanation of defective cell proliferation. PMID- 1903522 TI - Serum factors induce C-fos expression and rapid cell proliferation in adolescent but not in infant rat proximal tubule cells. AB - Kidney epithelial cells in short-term primary culture have been studied with regard to proliferative rate and expression on the c-fos protooncogene. The experiments were performed on subconfluent renal proximal tubule cells isolated from infant and adolescent rats. Proliferation was determined by 3H-thymidine autoradiography and nuclear content of c-fos protein by semiquantitative immunofluorescence. The basal proliferative rates in infant and adolescent renal proximal tubule cells were the same after 48 h of primary culture in Dulbecco's modified Eagle's medium with 10% FCS. Serum deprivation for 24 h caused a significant growth inhibition in both infant and adolescent cells. C-fos was expressed to the same extent in infant and adolescent serum-deprived cells. The rapid response to the addition of serum was markedly different in infant and adolescent cells. In adolescent cells, addition of serum led to a transient significant increase in the nuclear expression of c-fos protein, reaching a peak at 60 min. No increase in c-fos was seen in infant cells. In adolescent cells, the rate of proliferation increased 11-fold and 3H-thymidine labeling index reached 26.7 +/- 4.3%. In infant cells, the proliferative response to serum addition was significantly lower; the labeling index reached only 4.2 +/- 1.2%. It could be excluded that the attenuated response in infant cells was due to cell death or impaired metabolic function. The results imply that the principles of growth regulation change postnatally. PMID- 1903524 TI - Composition of plasma ApoA-I-containing lipoprotein particles in children and adults. AB - The purpose of this study was to examine sex- and age-related differences in the concentration and composition of lipoprotein particles containing apoA-I (LP-A-I) and those containing apoA-I and apoA-II (LP-I:A-II), the main HDL as defined by their apolipoprotein composition. Lipoproteins were isolated by immunoaffinity chromatography of whole plasma from 16 normal prepubertal children and 15 normal male and female adults using "pan"-MAb to apoA-I and apoA-II. Although there was no difference between children and adults in the concentration of LP-A-I:A-II, adult females had significantly higher levels of LP-A-I than either children or adult males. Main differences between children and adults as well as between adult males and females were in the apolipoprotein composition of the lipoprotein particles; children had the highest content of minor apolipoproteins (apoC and apoE) in LP-A-I but the lowest in LP-A-I:A-II. The lipid/apolipoprotein ratios of LP-A-I and LP-A-I:A-II were significantly higher in children and women than in men. The LP-A-I and LP-A-I:A-II contained 75% of the total plasma apoC and apoE in women and children but only 50% in men. However, in all three groups, 70-90% of the minor HDL apolipoproteins were associated with LP-A-I:A-II. The nonmolar ratios of minor apolipoproteins in LP-A-I and LP-A-I:A-II and the sex- and age related differences in apoA-I/apoA-II ratios of LP-A-I:A-II suggest that both lipoproteins may consist of a spectrum of lipoprotein subfamilies differing in their apolipoprotein composition.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1903525 TI - Characteristics of neonatal intensive care unit patients in North Carolina: a cross-sectional survey. AB - A shortage of neonatal intensive care facilities has been encountered in some areas of the country including North Carolina. To examine possible solutions to this health care delivery problem, a cross-sectional survey of all the neonatal intensive care units in North Carolina was performed to examine characteristics of patients occupying the beds in these facilities. It was found that a substantial amount of chronic care is now occurring in neonatal intensive care beds, with 38% of occupants of neonatal intensive care beds being 31 days of age or older and 3% being mechanically ventilated at 91 days of age or older. In addition, according to criteria established for this study, a substantial number of "convalescent" patients (32%) were occupying beds in neonatal intensive care units. It is concluded that an increase in both intermediate/convalescent care beds and establishment of chronic care facilities in North Carolina, rather than an increase in intensive care beds in these units, would alleviate the shortage of neonatal intensive care facilities. Further, the characteristics of the population occupying neonatal intensive care unit beds should be considered by health planners in addition to occupancy rate, when new facilities are being established. PMID- 1903526 TI - Preparation of lyophilized heat-treated cryoprecipitates from a small pool of plasma obtained by apheresis. AB - A method was developed for the batch-wise production of small-pool lyophilized heat-treated cryoprecipitates in a regional Blood Bank. Ten vials of final product were derived from twenty 600 g apheresis plasma donations. We found 384 IU of factor VIII per vial and a specific activity of 0.20 IU per mg total protein. Production recovery was 340 IU of factor VIII per kg plasma. The method was easy to perform and gave a product of good quality. PMID- 1903527 TI - Quality control programme for the preparation of small-pool lyophilized heat treated cryoprecipitates. AB - International and national documents on and standards for quality control have been introduced for Blood Banks. Recently, the Standard Registration Document and a National Health Authority Licence for factor VIII preparations based on the Document were introduced in the Netherlands. In the course of developing a preparation of lyophilized heat-treated cryoprecipitates in our Blood Bank, we used this Standard Registration Document and the good pharmaceutical manufacturing practices to design a quality control protocol. The aim of this protocol was to provide documented evidence on the quality of both our product and the production process. The protocol included the validation or revalidation of individual installations and procedures used during production, validation of the whole process and quality control of routine production. With our quality protocol we have been able to demonstrate that our preparation is consistently of the intended quality. PMID- 1903528 TI - [A case of acute monocytic leukemia cutis treated with total skin electron beam irradiation]. AB - A 35-year-old man with acute monocytic leukemia (AMoL) cutis was treated with total skin electron beam irradiation (TSEBI), because the widespread skin infiltration of AMoL appeared after induction chemotherapy. A skin nodule was authenticated as leukemic cell by biopsy. The patient was irradiated 4 times a week with 200 cGy per fraction to a total dose of 1200 cGy, using 6 MeV electrons from 8 directions. The therapy was accomplished separately on the upper and lower halves of the body. Focus-skin distance was 310 cm. An acrylic plate applicator 1 cm in thickness was used. The dimensions were 90 x 90 cm inside length and 90 cm in height. After completion of radiotherapy, the nodular lesions of the skin nearly disappeared. Although the patient survived only 3.5 months after beginning of radiotherapy due to systemic relapse, recurrence of the skin nodule was not seen. In this case TSEBI was therefore a useful treatment for skin infiltration of AMoL. PMID- 1903529 TI - [The use of antioxidants in the complex therapy of patients with infiltrating pulmonary tuberculosis]. AB - Clinical and laboratory investigations examined the possibility of a lower load of antibacterial drugs (ABD) in combination with the two antioxidants, alpha tocopherol and sodium thiosulfate, in combined therapy of patients with infiltrative pulmonary tuberculosis. Higher efficacy of two ABDs supplemented by two antioxidants than three or more ABDs was evidenced by a shorter period of sputum negativity (1.6 +/- 0.26 and 2.7 +/- 0.27 months; p less than 0.01) and higher rates of cavity closure (95.6 +/- 4.3 and 63.2 +/- 6.7%; p less than 0.05). PMID- 1903530 TI - [The use of a bacteriological method to detect an exacerbation in patients with cirrhotic tuberculosis of the lungs]. PMID- 1903531 TI - [The use of chicken embryos for culturing L-form of Mycobacterium tuberculosis]. PMID- 1903532 TI - [Determination of resistance of Mycobacterium tuberculosis to pyrazinamide by radiometric method]. PMID- 1903533 TI - [Effects of isoniazid and rifampicin on cell elements of cultured intact pulmonary tissue from experimental animals]. PMID- 1903534 TI - Photoactivation of the 2-(methylthio)ethanesulfonic acid reductase from Methanobacterium. AB - Inactive 2-(methylthio)ethanesulfonic acid (CH3-S-CoM) reductase was partially activated by exposure to light. This simplified system replaces the complex enzymatic system of protein components A2, A3a, A3b, and ATP, which previously represented the only available means of reactivating the enzyme. Components necessary for light activation include N-(7-mercaptoheptanoyl)-L-threonine O3 phosphate (HS-HTP), CH3-S-CoM, titanium(III) citrate [Ti(III)Cit], and light above 400 nm. Photoactivation was inhibited by known inhibitors of methanogenesis: 2-bromoethanesulfonate (BES), N-(6-mercaptohexanoyl)-L-threonine O3-phosphate, N-(8-mercaptooctanoyl)-L-threonine O3-phosphate, and sodium dithionite. Methanogenesis continued when the light-activated reaction mixture was incubated in the dark. Although the specific activity was low (35 nmol of CH4 per h per mg of protein) the reaction products methane and the unsymmetrical disulfide of 2-mercaptoethanesulfonate (HS-CoM) and HS-HTP were identified. We were unable to photoactivate a reaction mixture containing the isolated prosthetic group, native F430, or its analogues. PMID- 1903535 TI - Ferritin mRNA: interactions of iron regulatory element with translational regulator protein P-90 and the effect on base-paired flanking regions. AB - The ferritin iron regulatory element (IRE), a conserved sequence of 28 nucleotides in a hairpin loop, is a conserved mRNA-specific translational regulatory element; flanking the IRE are regions of varying sequence, which form 9-17 base pairs close to the 5' cap. P-90 is a ferritin mRNA-specific translation regulatory protein purified from animal liver and reticulocytes. To study the P 90-RNA interaction, protein nucleases (RNase S1 and T1) and chemical nucleases FeEDTA and/or 1,10-phenanthroline-Cu were used as probes of an oligonucleotide (n = 55), containing the IRE and flanking regions (FL), and natural ferritin mRNA. Footprints and "toeprints" showed that P-90 binding was confined to the stem and loop of the IRE itself. However, P-90 altered the structure of the flanking region by increasing base stacking or helicity (RNase V1 sensitivity). Comparison of the reactivity of the IRE and flanking regions in natural mRNA and the 55-mer showed that long-range interactions included protecting bulges, single-stranded, and stacked regions from protein nucleases as well as stabilizing the P-90-RNA interaction. Structural integration of the IRE with the base-paired flanking regions was indicated by common features of reactivity (periodic hypersensitivity to FeEDTA) and changes in the FL region caused by P-90. The increased secondary structure of the IRE flanking regions caused by P-90 binding to the IRE provides a likely mechanism for blocking initiation of ferritin mRNA translation, since the combined structure (IRE + FL) is so close (8-17 nucleotides) to the cap. PMID- 1903537 TI - A gene homologous to the subunit-2 gene of NADH dehydrogenase is essential to inorganic carbon transport of Synechocystis PCC6803. AB - A clone that transforms the RKa mutant of Synechocystis PCC6803 defective in inorganic carbon (Ci) transport to the wild-type phenotype was isolated from a cyanobacterial genomic library. The clone contained an 11.8-kilobase-pair DNA insert. Sequencing of the insert DNA in the region of the mutation in RKa revealed an open reading frame (designated as ndhB), which showed extensive amino acid sequence homology to the subunit-2 genes of NADH dehydrogenase (EC 1.6.99.3) (ndhB) of chloroplasts and mitochondria. The homology was much stronger with the chloroplast genes. Sequence analysis of the ndhB gene of RKa mutant revealed a G- --A substitution that results in a Gly----Asp substitution in the deduced amino acid. A defined mutant (M55), constructed by inactivating the ndhB gene in wild type Synechocystis, required high CO2 conditions for growth and was unable to transport CO2 and HCO3- into the intracellular Ci pool. The results indicate that the ndhB gene is required for Ci transport. Dark respiration was also depressed by the inactivation of the ndhB gene. A possible role of the ndhB gene product in the energization of Ci transport is discussed. PMID- 1903536 TI - Reshaping a therapeutic CD4 antibody. AB - An immunosuppressive rat antibody (Campath-9) against human CD4 has been reshaped for use in the management of autoimmunity and the prevention of graft rejection. Two different forms of the reshaped antibody were produced that derive their heavy chain variable region framework sequences from the human myeloma proteins KOL or NEW. When compared to a chimeric form of the CD4 antibody, the avidity of the KOL-based reshaped antibody was only slightly reduced, whereas that of the NEW-based reshaped antibody was very poor. The successful reshaping to the KOL based framework was by a procedure involving the grafting of human framework sequences onto the cloned rodent variable region by in vitro mutagenesis. PMID- 1903538 TI - Human X-box-binding protein 1 is required for the transcription of a subset of human class II major histocompatibility genes and forms a heterodimer with c-fos. AB - A complementary DNA encoding a member of the leucine-zipper class of proteins (human X-box-binding protein, hXBP-1) that binds to the 3' end of the conserved X box (X2) of the HLA-DRA major histocompatibility complex gene was recently described. Further gel-retardation analysis has demonstrated that hXBP-1 also binds to HLA-DPB X2 but not to other X2 sequences. Transient transfection of a mammalian expression vector with the hXBP-1 cDNA inserted in the antisense orientation represses the surface expression of HLA-DR and HLA-DP in Raji cells. Cotransfection of the antisense hXBP-1 vector with a HLA-DRA/chloramphenicol acetyltransferase (but not a HLA-DQB/chloramphenicol acetyltransferase) reporter plasmid decreases chloramphenicol acetyltransferase activity in Raji cells and in gamma-interferon-treated HeLa cells relative to cells cotransfected with a control antisense vector. Moreover, hXBP-1 is shown to form a stable heterodimer with the product of the c-fos protooncogene. These data suggest that the hXBP-1 c fos heterodimer is critical for the transcription of a subset of the human class II major histocompatibility complex genes and that the regulatory mechanisms for the different class II genes are distinct. PMID- 1903539 TI - Modulation of transcription factor NF-kappa B binding activity by oxidation reduction in vitro. AB - NF-kappa B is a widely used regulator of inducible and tissue-specific gene control. In the cytosol, when complexed to an inhibitory molecule, I kappa B, NF kappa B is in an inactive form and cannot bind DNA. Activation of cells with appropriate stimuli results in the dissociation of NF-kappa B from I kappa B and its translocation to the nucleus as an active binding protein. We now demonstrate that NF-kappa B binding in vitro can be inhibited by agents that modify free sulfhydryls. Binding is eliminated after treatment with N-ethylmaleimide, an alkylating agent, and diamide, an oxidizing agent. The diamide effect can be reversed by 2-mercaptoethanol. Further, 2-mercaptoethanol acts synergistically with deoxycholate plus Nonidet P-40 in converting inactive cytosolic NF-kappa B to an active DNA-binding form. It is therefore possible that modulation of the redox state of NF-kappa B could represent a post-translational control mechanism for this factor. PMID- 1903540 TI - Linkage of recognition and replication functions by assembling combinatorial antibody Fab libraries along phage surfaces. AB - We describe a method based on a phagemid vector with helper phage rescue for the construction and rapid analysis of combinatorial antibody Fab libraries. This approach should allow the generation and selection of many monoclonal antibodies. Antibody genes are expressed in concert with phage morphogenesis, thereby allowing incorporation of functional Fab molecules along the surface of filamentous phage. The power of the method depends upon the linkage of recognition and replication functions and is not limited to antibody molecules. PMID- 1903541 TI - Immunoglobulin variable-region-like domains of diverse sequence within the major histocompatibility complex of the chicken. AB - The highly polymorphic B-G antigens are considered to be part of the major histocompatibility complex (MHC) of the chicken, the B system of histocompatibility, because they are encoded in a family of genes tightly linked with the genes encoding MHC class I and class II antigens. To better understand these unusual MHC antigens, full-length B-G cDNA clones were isolated from B21 embryonic erythroid cell cDNA library, restriction-mapped, and sequenced. Five transcript types were identified. Analysis of the deduced amino acid sequences suggests that the B-G polypeptides are composed of single extracellular domains that resemble immunoglobulin domains of the variable-region (V) type, single membrane-spanning domains typical of integral membrane proteins, and long cytoplasmic tails. Sequence diversity among the five transcript types was found in all domains, notably including the B-G immunoglobulin V-like domains. The cytoplasmic tails of the B-G antigens are made up entirely of units of seven amino acid residues (heptads) that are typical of an alpha-helical coiled-coil conformation. The heptads vary in number and sequence between the different transcripts. The presence within B-G polypeptides of polymorphic immunoglobulin V like domains warrants further investigations to determine the degree and nature of variability within this domain in these unusual MHC antigens. PMID- 1903542 TI - A more biologically plausible learning rule for neural networks. AB - Many recent studies have used artificial neural network algorithms to model how the brain might process information. However, back-propagation learning, the method that is generally used to train these networks, is distinctly "unbiological." We describe here a more biologically plausible learning rule, using reinforcement learning, which we have applied to the problem of how area 7a in the posterior parietal cortex of monkeys might represent visual space in head centered coordinates. The network behaves similarly to networks trained by using back-propagation and to neurons recorded in area 7a. These results show that a neural network does not require back propagation to acquire biologically interesting properties. PMID- 1903543 TI - Human immunodeficiency virus infection of human lymph nodes in the SCID-hu mouse. AB - The SCID-hu mouse is a small animal in which human hematolymphoid organs can be engrafted and maintained in vivo. In this study, parameters are described for reproducible infection of SCID-hu mice after i.v. inoculation. Infection was found to be dependent upon the time after inoculation, the virus isolate, the titer of virus, and the human target organ implanted into the mouse. Ten to 14 days after the i.v. administration of HIV isolates derived freshly from patients (e.g., JR-CSF, JR-FL, SM), 100% of engrafted human lymph nodes in SCID-hu mice were infected; greater than 95% of these animals were also viremic. Implants of human thymus or connective tissue, as well as the endogenous murine hematolymphoid organs, were not infected. As demonstrated by a combination of in situ hybridization and immunohistochemistry, both T-lymphoid and myelomonocytic lineage cells were infected in this system. HIV isolates that have been adapted to growth in vitro (e.g., HTLV-IIIb) were not infectious. When either 3'-azido-3' deoxythymidine (AZT) or 2',3'-dideoxyinosine (ddIno) was administered to SCID-hu mice before HIV infection, the animals were protected in dose ranges similar to those used in man. This animal model may now be used as an efficient intermediate step between the lab and the clinic to study the infectious process in vivo and to best select efficacious antiviral compounds against HIV. PMID- 1903544 TI - Spo0A binds to a promoter used by sigma A RNA polymerase during sporulation in Bacillus subtilis. AB - Examination of the effects of 56 single-base-pair substitutions in the spoIIG promoter and studies of the interaction of the spo0A product (Spo0A) with this promoter in vitro demonstrated that Spo0A acts directly to enable this promoter to be used by sigma A-associated RNA polymerase (EC 2.7.7.6). The spoIIG operon from Bacillus subtilis is transcribed during sporulation by a form o RNA polymerase containing sigma A, the primary sigma factor in vegetative cells. The spoIIG promoter is unusual in that it contains sequences that are similar to those found at the -10 and -35 regions of promoters that are used by sigma A associated RNA polymerase, but these sigma A-like recognition sequences are separated by 22 base pairs rather than the typical 17 or 18 base pairs. We found that single-base-pair substitutions in the around the -35-like sequence, and substitutions in a region upstream from this position, around position -87, reduced promoter activity. DNase I protection and electrophoretic gel mobility shift assays were used to demonstrate that Spo0A binds specifically to these regions in vitro. Evidently, the -35-like sequence is part of a Spo0A binding site and therefore is possibly not a sigma A-recognition sequence. These results support a model in which Spo0A activates the spoIIG promoter after the onset of endospore formation. PMID- 1903546 TI - Identification of a region that influences host range of the streptococcal conjugative plasmid pIP501. AB - pIP501 is a member of a group of conjugative plasmids that are self-transmissible to a wide variety of streptococci as well as to other gram-positive bacteria. Several pIP501 restriction fragment deletion derivatives have been isolated and characterized. In this paper we describe one such derivative (pVA1702) which was conjugally proficient but had a limited host range. The loss of host range ability was seen as decreased conjugal transfer from Enterococcus faecalis to Streptococcus sanguis and was coincident with the deletion of a 4.5-kb DNA fragment. Transformation of pVA1702 into S. sanguis also was dramatically reduced as compared to its progenitor, suggesting the 4.5-kb fragment encoded a factor(s) necessary for stable maintenance in this host but not in E. faecalis. These observations suggest that pIP501 employs specific mechanisms enabling its maintenance in certain gram-positive bacteria. PMID- 1903545 TI - Altered phosphorylation of tau protein in heat-shocked rats and patients with Alzheimer disease. AB - Six hours after heat shocking 2- to 3-month-old male and female Sprague-Dawley rats at 42 degrees C for 15 min, we analyzed tau protein immunoreactivity in SDS extracts of cerebrums and peripheral nerves by using immunoblot analysis and immunohistochemistry with the anti-tau monoclonal antibody Tau-1, which recognizes a phosphate-dependent non-phosphorylated epitope, and with 125I labeled protein A. In the cerebral extracts, we found altered phosphorylation of tau in heat-shocked females, characterized by a marked reduction in the amount of nonphosphorylated tau, a doubling of the ratio of total (phosphorylated plus nonphosphorylated) tau to nonphosphorylated tau, and the appearance of the slowest moving phosphorylated tau polypeptide (68 kDa). Similar, but milder, changes were observed in male rats. These changes progressively increased in females from 3 to 6 h after heat shocking. In contrast, both phosphorylated tau and nonphosphorylated tau were reduced in peripheral nerves after heat shocking. In immunoblots of SDS extracts from Alzheimer disease-affected brain, the two slowest moving phosphorylated tau polypeptides (62 kDa and 66 kDa, respectively) were detected by Tau-1 after dephosphorylation and by Tau-2 (an anti-tau monoclonal antibody that recognizes a phosphate-independent epitope) without prior dephosphorylation only in regions that contained tau immunoreactivity in histologic preparations. In addition, quantitative immunoblot analysis of cortex and the underlying white matter with Tau-1 and 125I-labeled protein A showed that the amount of phosphorylated tau progressively increased in the Alzheimer disease affected cerebral cortex, while concurrently a proportionally lesser amount of tau entered the white matter axons. The similar findings for the rat heat-shock model and Alzheimer disease suggest that life stressors may play a role in the etiopathogenesis of Alzheimer disease. PMID- 1903547 TI - Effect of PD 128763, a new potent inhibitor of poly(ADP-ribose) polymerase, on X ray-induced cellular recovery processes in Chinese hamster V79 cells. AB - The modifying effects of PD 128763 (3,4-dihydro-5-methyl-1(2H)-isoquinolinone), a potent inhibitor of poly(adenosine-diphosphate (ADP)-ribose) polymerase, on radiation-induced cell killing were examined in Chinese hamster V79 cells. This compound has an IC50 value against the purified enzyme approximately 50X lower than 3-aminobenzamide (3-AB), a widely used specific inhibitor of the enzyme. Exposure of exponentially growing cells to a noncytotoxic concentration (0.5 mM) of PD 128763 for 2 h immediately following X irradiation increased their radiation sensitivity, modifying both the shoulder and the slope of the survival curve. When recovery from sublethal damage and potentially lethal damage was examined in exponential and plateau-phase cells, respectively, postirradiation incubation with 0.5 mM PD 128763 was found not only to inhibit both these processes fully, but also to enhance further the level of radiation-induced cell killing. This is in contrast to the slight effect seen with the less potent inhibitor, 3-AB. The results presented suggest that the mechanism of radiosensitization by PD 128763 is related to the potent inhibition of poly(ADP ribose) polymerase by this compound. PMID- 1903548 TI - [Biological activity of gamma-irradiated serum albumin]. AB - Gamma-irradiated serum albumin activated L-tyrosine oxidation to 3,4-dioxyphenyl alanine (DOPA) and forms adducts with DOPA oxidation products. These adducts are more resistant to proteolysis and have bactericidal and mutagenic capacity. A possible role of such adducts in a radiation damage to the organism is discussed. PMID- 1903549 TI - [Grand mal seizure. Laminar heterotopy of the gray substance]. PMID- 1903550 TI - Pertussis toxin blocks the dipsogenic actions of carbachol, but does not block the dipsogenic and pressor actions of angiotensin II. AB - Rats were tested for dipsogenic and pressor responses to intracerebroventricularly (icv) administered Ang II and for dipsogenic responses to icv administered carbachol in the absence and presence of pertussis toxin, also administered icv. Pertussis toxin did not inhibit the pressor or dipsogenic responses to Ang II, but did inhibit the dipsogenic responses to carbachol. This suggests that the pressor and dipsogenic responses to Ang II in the brain are not mediated by a pertussis toxin-sensitive G protein, but that the muscarinic cholinergic dipsogenic response is mediated by a pertussis toxin-sensitive G protein. PMID- 1903551 TI - [The control of respiration in pulmonary fibrosis. The effect of O2 and CO2]. AB - We have studied the mode of ventilation and chemosentivity in 10 patients suffering from pulmonary fibrosis. The total lung capacity was on average 63.5 +/ 8% of the predicted. Their static compliance was 0.078 +/- 0.05 l.cm of water. The patients were studied in the prone position breathing ambient air then on hyperoxia. The response to CO2 was assessed according to the rebreathing method of Read. The results of these patients were compared with those of 11 normal subjects. The ventilation at rest was normal, with a shortened respiratory time and a Ti/Ttot ratio which was lowered. The occlusion pressure (P0.1) was very much higher than that in normal subjects. This rise was correlated with an increase in pulmonary elastance and a reduction in vital capacity. The correction of hypoxia was without effect on the respiratory parameters. In relation to normal subjects the ventilatory response to carbon dioxide in fibrotics was decreased whilst the response of the P0.1 was increased expressing central hyperactivity. In conclusion, fibrotic patients have normal ventilation in spite of an increase in inspiratory work. This normal ventilation results from hyperactivity of the respiratory centre, as in the hyperventilation induced by carbon dioxide when at rest. PMID- 1903552 TI - Neurologic causes of learning disabilities. PMID- 1903553 TI - Functional effects of cytochrome P450 arachidonate metabolites in the kidney. PMID- 1903555 TI - [Unnecessary bacteriologic studies]. PMID- 1903554 TI - Renal effects of dietary protein excess and deprivation. PMID- 1903556 TI - [Ethics and money]. PMID- 1903557 TI - Drugs that dissolve clots. PMID- 1903558 TI - Effect of misoprostol and antacids on gastric and duodenal mucosal enzyme activities in duodenal ulcer patients. AB - The activities of 11 marker enzymes from the gastric and duodenal mucosa were determined in 15 patients with active duodenal ulcer disease before therapy, after 4 weeks of therapy with the prostaglandin E1 analogue misoprostol, 400 micrograms twice daily, and after another 4 weeks without any therapy. Another 15 patients were given a high-dose liquid antacid regimen. The activities were measured in homogenized material obtained with forceps through an endoscope. The healing rates of the two groups at 4 weeks were 53% and 80%, respectively. No changes in mucosal inflammation were noted during therapy. During treatment with misoprostol the activities in the descending duodenum of the membrane enzymes alkaline phosphatase, leucyl-beta-naphthylamidase, gamma-glutamyltransferase, and 5'-nucleotidase increased towards the values seen in normal controls. Despite a higher healing rate, no changes in the enzyme activities occurred in the group given high-dose antacid therapy. Four weeks after cessation of therapy the enzyme activities in the misoprostol group were not significantly different from the pretreatment values. In the biopsy specimens from the duodenal bulb the activities of monoamine oxidase fell during treatment with misoprostol and were restored to the pretreatment activity when therapy was stopped. In the stomach mucosa the enzyme activities were largely unchanged during treatment with both misoprostol and antacids. These results indicate that misoprostol and antacids have different mechanisms of action but may also suggest that the demonstrated enzymic changes are unrelated to the healing process. PMID- 1903559 TI - Spectral tuning of pigments underlying red-green color vision. AB - Variations in the absorption spectra of cone photopigments over the spectral range of about 530 to 562 nanometers are a principal cause of individual differences in human color vision and of differences in color vision within and across other primates. To study the molecular basis of these variations, nucleotide sequences were determined for eight primate photopigment genes. The spectral peaks of the pigments specified by these genes spanned the range from 530 to 562 nanometers. Comparisons of the deduced amino acid sequences of these eight pigments suggest that three amino acid substitutions produce the approximately 30-nanometer difference in spectral peaks of the pigments underlying human red-green color vision, and red shifts of specific magnitudes are produced by replacement of nonpolar with hydroxyl-bearing amino acids at each of the three critical positions. PMID- 1903560 TI - Spinal epidural hematoma causing cord compression after tissue plasminogen activator and heparin therapy. AB - Bleeding is the most serious complication of thrombolytic therapy and limits its usefulness. We have reported a case of epidural hematoma, a rare occurrence after combined therapy with tissue plasminogen activator (TPA) and heparin. We emphasize that in patients treated with thrombolytic agents, any trauma may increase the risk of bleeding. The sudden onset of back pain and neurologic deficits should alert the clinician to the possibility of spinal hematoma with cord compression. PMID- 1903561 TI - [Male infertility. Examination of the patients]. PMID- 1903562 TI - Health expenditures in Texas for 1987. AB - Total, per capita, and state government health spending by category of service for 1987 were estimated along with the distribution of spending by sources of payment. Definitions, methods, and sources of data are similar to those used by the US Health Care Financing Administration in estimating national health care expenditures and payments. Comparisons are made with prior-years' spending and with estimates of spending at the national level. Spending and financing patterns are identified and possible explanations are discussed. PMID- 1903563 TI - Speaking out as a physician--not a provider. PMID- 1903564 TI - Hospital DRG coding: how physicians can help. PMID- 1903565 TI - [Diphosphonates in the treatment of osteoporosis]. AB - The efficacy of diphosphonates in the treatment of diseases with increased osteoclastic bone resorption has been clearly demonstrated. Recent results show that these substances are also effective in the treatment of osteoporosis. Intermittent application of the first generation bisphosphonate, etidronate, up to three years is free of risk, stabilizes trabecular bone density after two years and seems to decrease the progression of deformations of the vertebral column in women with postmenopausal osteoporosis and vertebral fractures. In order to prove this benefit clearly, further studies of longer duration are needed. Continuous application of the second generation bisphosphonate, pamidronate, leads to an increased density of vertebral bodies in osteoporotic patients up to four years and a decreased frequency of new vertebral fractures. These results must however still be confirmed by controlled studies with more patients. There are also indications that a continuous treatment with pamidronate is able to prevent the steroid-induced bone loss. There are on the contrary no results about the effect of bisphosphonates on the fracture rate of peripheral bones and only limited results about the use of bisphosphonates in the prevention of postmenopausal bone loss. Before bisphosphonates can be offered as an alternative solution to hormone substitution therapy, we still need extensive studies about efficacy and safety. PMID- 1903566 TI - Inhibitory effects of radical scavengers on diacylglycerol-promoted transformation in BALB/3T3 cells. AB - To discover the relationship between the activation of protein kinase C and the generation of reactive oxygen in the tumor promotion process, we investigated the effects of radical scavengers on diacylglycerol-promoted transformation in BALB/3T3 cells. Superoxide dismutase (SOD) showed inhibitory effects on both 1 oleoyl-2-acetylglycerol (OAG)-promoted and diolein-promoted transformation. Catalase (CT) suppressed the promoting effects of diolein by up to 70%. Mannitol (MT), a hydroxyl radical (.OH) scavenger, inhibited diacylglycerol-promoted transformation dose-dependently. These results suggest that activation of protein kinase C alone is insufficient and that generation of reactive oxygen accompanied by activation of the enzyme is essential to the promotion process in BALB/3T3 cells. PMID- 1903567 TI - Inhibition of the 17 beta-estradiol-induced and constitutive expression of the cellular protooncogene c-fos by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the female rat uterus. AB - Acute administration of 17 beta-estradiol (5 micrograms/rat) to 25-day-old female Sprague-Dawley rats resulted in an increase of uterine mRNA for the cellular oncogene c-fos. The c-fos mRNA levels were significantly elevated 12 and 24 h after exposure to the hormone (232 and 164% of control values) and the elevation was not observed after 48 h. In contrast, treatment of the animals with either 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or 6-methyl-1,3,8 trichlorodibenzofuran (MCDF) resulted in a dose-dependent decrease in constitutive uterine c-fos mRNA levels. In rats co-treated with 17 beta-estradiol plus TCDD or MCDF, it was apparent from the results that the halogenated aromatic hydrocarbons significantly inhibited the estrogen-induced increases in uterine c fos mRNA levels. These observations further extend the diverse spectrum of antiestrogenic effects caused by TCDD and related compounds and also show an interaction between TCDD and the constitutive expression of the c-fos proto oncogene in the female rat uterus. PMID- 1903568 TI - Genetics of prion infections. AB - Although the infectious prions causing scrapie and several human transmissible neurodegenerative diseases resemble viruses in many respects, molecular and genetic analyses indicate that prions are fundamentally different from viruses in their structure and the mechanisms by which they cause disease. The only macromolecule that has been identified in infectious prion preparations is a disease-specific isoform of the prion protein, which is encoded by a host gene. A growing body of data supports the contention that prion infections represent a novel host-pathogen interaction. PMID- 1903569 TI - Origins of BSE. PMID- 1903570 TI - Origins of BSE. PMID- 1903571 TI - The effects of repeated administration of various chelating agents on the removal of strontium from the mouse. AB - The effects of repeated ip administration of diethylenetriaminepentaacetic acid (DTPA), Kryptofix 222, 1,4,7,10,13,16-hexaoxacyclooctadecane (18-crown-6), ethylenglycol-bis-(beta-amino-ethylether)-N,N'-tetraacetic acid (EGTA), and Kryptofix 5 on the distribution and excretion of sc-injected strontium were investigated in male Swiss mice. Groups of 20 animals received 95 mg strontium nitrate/kg, and 10 min later ip treatment with one of the chelators or 0.9% saline was initiated and continued for 10 d. The animals were housed in plastic metabolism cages, and urine and feces were collected daily during the period of treatment. At the end of this period, the animals were killed and the concentration of strontium determined in their tissues. Only Kryptofix 5 and EGTA significantly increased the amount of strontium excreted into feces, whereas none of the chelators significantly enhanced the urinary elimination of strontium. Treatment with Kryptofix 5 significantly decreased the concentration of strontium in all tissues analyzed. Kryptofix 5 was the most effective agent of those tested in the removal of strontium after a single dose of strontium nitrate. PMID- 1903572 TI - Epidemiology of absence epilepsy. II. Typical absences in children with encephalopathies. AB - A population-based study of absence epilepsy in Swedish children, aged 0-15 years, comprised cases selected on the basis of EEG criteria. Absence epilepsy was found in 119 of the 134 children with 3 Hz spike-and-wave discharges, and 12 of these 119 (10.1%) had typical absences in addition to other generalized seizures and slow irregular spike-and-wave activity on the EEG. The mean annual incidence of this type of absence epilepsy was 0.7/100,000. The median age at onset of absences was 6 years. Eight of the 12 patients had neurological abnormalities and/or severe mental retardation. The patients constitute a heterogeneous group of encephalopathies. They may have a genetic predisposition for absence epilepsy, causing it to appear during the course of a more severe, encephalopathy related, type of epilepsy. PMID- 1903573 TI - Evaluation of CSF shunt function: value of functional examination with contrast material. AB - Functional positive-contrast shuntography includes a patency check of both limbs of the shunt and the shunt valve by fluoroscopy following the injection of an iodinated contrast agent (anatomic shuntogram) and an assessment of the adequacy of ventricular fluid drainage under physiologic conditions by using serial CT scans to assess the rate of iodine dissipation from the ventricular system (physiologic shuntogram). To demonstrate its efficacy and utility, 82 functional shuntograms were obtained in 55 patients. Fifty-one of the 82 studies were abnormal. Of these, 22 demonstrated patency of both the proximal and distal limbs with an accompanying slow dissipation of contrast material after injection (21 of 22 patients were adults). Eighteen of these 22 patients improved following the reduction of shunt drainage pressure. In the case of frank shunt obstruction, the site of obstruction was delineated clearly in all 29 cases. Correlation of clinical outcome with test results confirmed the utility of this technique, especially when applied to the shunted adult hydrocephalic patient whose response to the shunt had been inadequate. The technique described here allows the clinician to differentiate between physiologic and anatomic shunt failure and between shunt failure and normal shunt function. It also allows for precise localization of the shunt obstruction in anatomic shunt failure and for demonstration of physiologic shunt failure when shunt patency is demonstrated in the presence of the slow dissipation of intraventricular contrast medium. PMID- 1903574 TI - Diagnosis of carotid artery stenosis: comparison of 2DFT time-of-flight MR angiography with contrast angiography in 50 patients. AB - Fifty patients underwent 2DFT time-of-flight MR angiography and intraarterial contrast angiography for evaluation of possible carotid atherosclerotic disease. The MR angiography technique employed contiguous axial flow-sensitive (short TR/TE) slices that were reformatted and postprocessed by using a maximum intensity projection algorithm to provide 16 angiographic views of the carotid arteries. Both studies were independently reviewed by two observers in a blinded manner. Carotid arteries were categorized as normal, mildly stenotic, moderately stenotic, severely stenotic, or occluded. For the 94 carotid arteries available for review, one observer reported a 70% agreement between the two techniques and the second observer reported a 56% agreement (p = .0001). The best correlation was in the severely stenotic category and the worst was in the occluded category. Agreement between observers was 67% for MR angiography and 72% for contrast angiography, which was similar to that between the two techniques. Although not all carotid atherosclerotic disease was visualized equally well, 2DFT time-of flight MR angiography had a good overall correlation with the "gold standard" of intraarterial contrast angiography, supporting its use as a screening technique. While further improvements are needed, use of MR angiography as the primary diagnostic tool for many patients with suspected carotid stenosis should continue to increase. PMID- 1903575 TI - Idiopathic growth hormone deficiency: MR findings in 35 patients. AB - Idiopathic growth hormone deficiency is a disorder that is not clearly understood. We therefore evaluated the MR scans of 35 patients with idiopathic growth hormone deficiency in an attempt to define more clearly the abnormalities of the hypothalamohypophyseal axis, determine the frequency of these abnormalities, and determine whether a relationship exists between the MR findings and the patient's clinical history and endocrine function. Patients with MR abnormalities fell into two groups; those with an ectopic neurohypophysis (15 patients, or 43%), which consisted of a neurohypophysis near the median eminence, absence of the infundibulum, and absence of the normal posterior pituitary bright spot; and those with a small anterior pituitary gland (15 patients, or 43%), which was an isolated finding in five patients and associated with an ectopic neurohypophysis in 10 patients. Examination of endocrine function identified two groups of patients: those with multiple hormone deficiencies and those with isolated growth hormone deficiency. An ectopic neurohypophysis was present in 87% of the first group and 10% of the second group. The anterior pituitary dysfunction in those with an ectopic neurohypophysis was thought to be related to the absent infundibulum, which normally houses the portal system. Our MR findings demonstrated that over 40% of patients with idiopathic growth hormone deficiency have an ectopic neurohypophysis and absence of the infundibulum. We believe that the growth hormone deficiency in these patients is related to the absent infundibulum. PMID- 1903576 TI - MR imaging in chronic partial epilepsy: role of contrast enhancement. AB - Gadopentetate dimeglumine was administered prospectively to 150 consecutive patients who had had partial epilepsy for longer than 1 year to determine whether it is routinely indicated for the diagnosis of this disorder. MR abnormalities correlating with clinical or electroencephalographically documented seizure foci were detected in 69 cases (46%). Contrast enhancement was seen in 33 of these lesions, but the presence of enhancement altered the original radiologic diagnosis in only 17 (11%) of 150 cases. In only two cases (1%) did contrast administration reveal lesions that were not definitely apparent on the unenhanced images. The utility of contrast administration could not be predicted on the basis of seizure type (simple or complex) or the presence of secondary generalization. Gadopentetate dimeglumine does not appear to be routinely required in the MR workup of patients with chronic partial epilepsy. It should be used selectively to clarify or better define the nature of abnormalities encountered on unenhanced images. PMID- 1903578 TI - Long-term care financing update. American Medical Association. PMID- 1903577 TI - Diagnosis of ruptured intracranial dermoid cyst: value MR over CT. AB - The CT and MR findings of seven patients with pathologically proved ruptured dermoid cysts were reviewed to analyze the MR characteristics and to see if MR evaluation had significant advantages over CT. In six cases, both CT and MR identified fatty material in the CSF spaces. Hemorrhage complicated preoperative diagnosis in one case. Patterns of extraaxial fat distribution were as follows: intraventricular fat/CSF levels (three patients), generalized subarachnoid spread (six patients), and localized subarachnoid spread with sulcal widening (one patient). There was no correlation between fat distribution and clinical symptoms. MR showed the vascular involvement better than CT did in five of seven cases, and showed extension of the cysts into the skull base in two cases. Signal intensity of the solid mass was low on T1-weighted MR images and inhomogeneously high on T2-weighted images, which correlated pathologically with the presence of crystal cholesterol, hair, sebaceous glands, and epithelial cells in all cases. On MR, brain parenchyma showed little edema or other reaction to the masses, which were typically large. The value of MR over CT in the examination of ruptured dermoid cysts is the conspicuity of the extent of subarachnoid spread, involvement of the extraaxial structures, and evidence of vascular compromise, which can obviate angiography. MR had no advantage over CT in making the initial diagnosis of ruptured dermoid, but it would be the preferred preoperative study. PMID- 1903579 TI - Possible mechanism of vascular reocclusion after initially successful thrombolysis with recombinant tissue-type plasminogen activator. AB - We studied the effects of urokinase (UK), pro-urokinase (pro-UK), and recombinant tissue-type plasminogen activator (rt-PA) on platelet aggregation and the production of thromboxane A2 (TXA2) in vitro. Both UK and pro-UK inhibited the platelet aggregation induced by adenosine 5'-diphosphate (ADP), collagen, or thrombin in a concentration-dependent manner. In contrast, although a low dose of rt-PA (5 to 10 x 10(4) U/ml) blunted platelet aggregability, a high dose (40 to 60 x 10(4) U/ml) led to platelet hyperaggregation. UK and pro-UK markedly inhibited TXA2 synthesis during ADP-induced platelet aggregation. Despite the significant reduction of TXA2 synthesis by 10 x 10(4) U/ml rt-PA, a concentration of 60 x 10(4) U/ml rt-PA had no effect on synthesis. These results indicate that UK and pro-UK each inhibit platelet function, but a high concentration of rt-PA enhances platelet aggregability. This finding may at least in part contribute to the high incidence of reocclusion after initially successful thrombolysis with rt PA. PMID- 1903580 TI - The acute effects of flecainide in the swine heart failing from incessant supraventricular tachycardia. AB - The acute hemodynamic and electrophysiologic effects of flecainide in tachycardia induced ventricular dysfunction were investigated using an animal model. Seven swine were initially (CON) evaluated by echocardiography and then by right heart catheterization and provocative electrical ventricular stimulation both before and after treatment with intravenous flecainide. Rapid atrial pacing at 210 to 240 beats/min (SVT) was then employed for 2 to 4 weeks until echocardiographic evidence of left ventricular dysfunction developed. Immediately upon termination of pacing, the above studies were repeated both before and after treatment with flecainide. Significant (p less than 0.0001) pacing-related hemodynamic effects on the cardiac output (CON:3.0 L/min versus SVT:1.6 L/min), right ventricular ejection fraction (CON:55% versus SVT:17%), and pulmonary wedge pressure (CON:8 mm Hg versus SVT:22 mm Hg) were observed. Pacing-related electrophysiologic effects included increases in the PR interval (CON:94 msec versus SVT:119 msec, p less than 0.001) and QTc interval (CON:418 msec versus SVT:450 msec, p = 0.016). With serum flecainide concentrations in the human therapeutic range, no significant effect on hemodynamic or electrophysiologic parameters in either the normal or failing heart were detected. Nonsustained ventricular tachycardia induced prior to pacing in one animal and after pacing in another animal was seen before but not following use of flecainide. No acute proarrhythmic effects were observed. In summary, intravenous flecainide had no significant acute adverse hemodynamic, electrophysiologic, or proarrhythmic effects in an animal model of tachycardia-induced ventricular dysfunction. PMID- 1903582 TI - Nitroglycerin-induced heparin resistance. PMID- 1903581 TI - Impaired heart rate variability in patients with chronic Chagas' disease. AB - Spectral analysis of heart rate variability was used to investigate the possible alteration in sympathovagal control of heart rate in patients with Chagas' disease. The study included 31 subjects, divided into three groups: controls, Chagas' 1 (subjects with only positive serology for Chagas' disease) and Chagas' 2 (subjects with positive serology and electrocardiographic abnormalities that are usually found in this disease). The subjects were studied during rest, while standing, and during handgrip exercise. With this approach, the low frequency (approximately 0.1 Hz) spectral component of R-R interval variability is considered to be a marker primarily of sympathetic activity, whereas the high frequency (approximately 0.25 Hz) component, which is related to respiration, seems mainly to reflect vagal activity. We observed significant (p less than 0.05) differences among the three groups during standing: although in the control subjects the low-frequency component increased (delta = 30 +/- 5 normalized units, nu), there was no increase in Chagas' 1 (delta = -1 +/- 8 nu) and Chagas' 2 (delta = -2 +/- 8 nu) patients. During handgrip exercise, another test that is capable of exciting sympathetic outflow, there was an increase of low frequency only in control subjects. These results confirm the occurrence of quantitative and assessable abnormalities in the neural control of heart rate variability in Argentinian patients with chronic Chagas' disease, even in the absence of heart failure. PMID- 1903583 TI - Nitroglycerin and intracranial hypertension. PMID- 1903584 TI - Vasodilators in the intensive care unit. PMID- 1903585 TI - Quantitation of energy expenditure by infrared thermography. AB - The objective of this study was to adapt infrared thermography (IRT) to measure heat loss in human beings. IRT images were digitized and a mean body surface temperature was computed; heat losses caused by radiation, convection, and evaporation were calculated by using these data. Because subjects were standing during the procedure a small amount of heat was conducted through the feet; this heat was ignored. Total heat loss measured by IRT was not significantly different from values calculated from simultaneous indirect calorimetry (IC) determinations in fasting health subjects and in postsurgical patients receiving a constant infusion of energy. In healthy subjects, after eating the patterns of response to IRT and IC were as predicted from previous direct calorimetry data. Heat loss measured by IC increased first, 30 min postprandially, followed by an increase in heat loss at 60 min as measured by IRT. It was concluded that IRT as a noninvasive method can be used to quantitate heat loss in human beings. PMID- 1903587 TI - Osteochondrodysplasia in Fryns syndrome. AB - Various skeletal abnormalities have been identified in roentgenograms of persons with Fryns syndrome, but to our knowledge, no histopathologic description of bone or cartilage has been published. We describe disordered endochondral and intramembranous bone formation in a premature female infant with Fryns syndrome. This infant and a full sibling (ie, had same set of parents) with Fryns syndrome in addition exhibited delayed ossification of the basiocciput and of cervical vertebral bodies, also previously undescribed in Fryns syndrome. These findings expand the spectrum of Fryns syndrome to include osteochondrodysplasia. PMID- 1903586 TI - Adipose-tissue fatty acid composition in recipients of long-term total parenteral nutrition (TPN). AB - Adipose-tissue fatty acid composition was studied in nine patients requiring long term total parenteral nutrition (TPN). The patients received 17 +/- 8% of total energy as soybean-oil emulsion (Intralipid) and 66 +/- 8% as glucose. Despite low intake of 9c-16:1, 11c-18:1, and 13c-18:1, adipose-tissue concentrations of these monounsaturated fatty acids were higher in the TPN patients than in free-living control subjects (P less than 0.05) and inversely correlated with the percent energy from fat (r = -0.56, P = 0.11; r = -0.64, P = 0.06; r = -0.81, P = 0.008, respectively). This suggests that these fatty acids accumulated from endogenous synthesis from carbohydrate and thus may be markers of the percent fat in the diet. The essential fatty acids, 18:2 and 18:3n-3, positively correlated with the percent energy from fat (r = 0.79, P = 0.01; r = 0.80, P = 0.01, respectively). Linear-regression analysis suggests that normal adipose-tissue stores of 18:2 and 18:3n-3 are maintained when intravenous soybean-oil emulsion provides 11-20% and 4-12%, respectively, of total energy. PMID- 1903588 TI - Factors associated with umbilical catheter-related sepsis in neonates. AB - To determine factors associated with risk for umbilical catheter-related sepsis, we studied neonates with one or more catheters in place for more than 3 days. Among 225 infants with 357 umbilical catheters, catheter-related sepsis occurred in 14 infants (6%). Catheter-related sepsis occurred in 5% of infants with umbilical arterial catheters and in 3% of infants with umbilical venous catheters. Staphylococcal species accounted for 71% of cases of catheter-related sepsis. Multiple logistic regression analysis revealed that very low birth weight and longer duration of antibiotic therapy were significantly associated with risk for umbilical arterial catheter-related sepsis. Increased risk for umbilical venous catheter-related sepsis was best predicted by the simultaneous occurrence of higher birth weight and infusion of hyperalimentation solution. Catheter duration correlated with duration of antibiotic therapy and with infusion of hyperalimentation solution for both types of catheters; however, in the multivariable analysis, duration of catheterization was not found to be a significant independent predictor of risk for catheter-related sepsis for either type of catheter. PMID- 1903589 TI - Risk factors associated with falls and injuries among elderly institutionalized persons. AB - A case-control study among 184 matched pairs of patients 65 years of age and older was undertaken to identify risk factors associated with falls and injuries in a long-term care facility in Baltimore, Maryland, in 1984-1985. Patients were matched on length of stay. Variables of interest included sociodemography, functional status, medications, and diagnoses. For all levels of care combined, the following factors were associated (p less than or equal to 0.01) with increased falls: being able to walk (relative odds (RO) = 4.0), age 90 years and older (RO = 3.8), a history of falling (RO = 5.0), and taking a vasodilator (RO = 3.0). Among the 184 fallers, the diagnosis of dementia (RO = 7.5) or taking a diuretic (RO = 7.2) was positively associated with injury (p less than or equal to 0.01). In each of the analyses, medications were associated with falls or injuries, suggesting a feasible intervention. The combination of a history of falling, being able to walk, and being 90 years of age or older increased the relative odds to 51.9 and could alert clinicians to identify and monitor high risk elderly persons in need of preventive measures. PMID- 1903590 TI - Congenital deficiency of a 20-kDa subunit of mitochondrial complex I in fibroblasts. AB - The first component of the mitochondrial electron-transport chain is especially complex, consisting of 19 nuclear and seven mitochondrion-encoded subunits. Accordingly, a wide range of clinical manifestations are produced by the various mutations occurring in human populations. In this study, we analyze the subunit structure of complex I in fibroblasts from two patients who have distinct clinical phenotypes associated with complex I deficiency. The first patient died in the second week of life from overwhelming lactic acidosis. Severe complex I deficiency was evident in her fibroblasts, since alanine oxidation was markedly reduced whereas succinate oxidation was normal. Absence of a 20-kDa subunit was demonstrable when newly synthesized proteins were immunoprecipitated from pulse labeled fibroblasts by anti-complex I antibody. Disordered assembly or decreased stability of the complex was suggested by deficiency of multiple subunits on Western immunoblots. The second patient exhibited a milder clinical phenotype, characterized by moderate lactic acidosis and developmental delay in childhood and by onset of seizures at 8 years of age. Oxidation studies demonstrated expression of the complex I deficiency in fibroblasts, but no subunit abnormalities were detected by immunoprecipitation or Western immunoblotting. This report demonstrates the utility of cultured fibroblasts in studying mutations affecting synthesis and assembly of complex I. PMID- 1903592 TI - Umbilical arterial and venous acid-base and blood gas values and the effect of chorioamnionitis on those values in a cohort of preterm infants. AB - Umbilical arterial and venous acid-base and blood gas values in uncomplicated premature births are similar to values that are reported in term infants and are unaffected by birth weight or gestational age. In this group of patients chorioamnionitis had no significant effects on umbilical arterial acid-base or blood gas values or on the percentage of patients that were born with acidemia. Apgar scores were significantly lower in the group with chorioamnionitis in spite of a virtual absence of acidemia, which again suggests that low Apgar scores alone do not confirm a diagnosis of birth asphyxia. PMID- 1903591 TI - Tyrosinase gene mutations associated with type IB ("yellow") oculocutaneous albinism. AB - We have identified three different tyrosinase gene mutant alleles in four unrelated patients with type IB ("yellow") oculocutaneous albinism (OCA) and thus have demonstrated that type IB OCA is allelic to type IA (tyrosinase negative) OCA. In an inbred Amish kindred, type IB OCA results from homozygosity for a Pro- --Leu substitution at codon 406. In the second family, type IB OCA results from compound heterozygosity for a type IA OCA allele (codon 81 Pro----Leu) and a novel type IB allele (codon 275 Val----Phe). In the third patient, type IB OCA results from compound heterozygosity for the same type IB allele (codon 275 Val-- -Phe) and a novel type IB OCA allele. In a fourth patient, type IB OCA results from compound heterozygosity for the codon 81 type IA OCA allele and a type IB allele that contains no identifiable abnormalities; dysfunction of this type IB allele apparently results from a mutation either well within one of the large introns or at some distance from the tyrosinase gene. In vitro expression of the Amish type IB allele in nonpigmented HeLa cells demonstrates that the Pro----Leu substitution at codon 406 greatly reduces but does not abolish tyrosinase enzymatic activity, a finding consistent with the clinical phenotype. PMID- 1903593 TI - Cost-effectiveness of prenatal testing for Chlamydia trachomatis. AB - We investigated the cost-effectiveness of strategies for screening pregnant women for Chlamydia trachomatis. Screening was not cost-effective unless certain conditions were met. Direct antigen testing of all pregnant women would be cost effective if the test cost less than $6.30 or the prevalence of infection exceeded 6%. However, the positive predictive value of the test was only 51%. Culturing was not cost-effective until the prevalence of infection exceeded 14.8%. If a direct antigen test cost less than $3.90 or prevalence exceeded 8.7%, direct antigen testing of all women and using culture to confirm positive direct antigen tests would be cost-effective. If a direct antigen test cost $8.00 and culture cost $25.00, the excess cost of performing a direct antigen test in all women and confirming positive results with culture would be $2.09 per pregnant woman. Screening all pregnant women for chlamydia is not cost-effective, but the excess cost is modest when direct antigen tests are used. PMID- 1903594 TI - Synergistic effect of intraperitoneally administered calcium channel blockade and recombinant tissue plasminogen activator to prevent adhesion formation in an animal model. AB - Previous reports have shown the benefits of calcium channel blockers and recombinant tissue plasminogen activator to prevent postoperative adhesion formation in animal models. To assess the potential benefit of synergistic therapy for the prevention of postoperative adhesion formation, these agents were studied in a rabbit uterine horn model. Four groups of New Zealand White rabbits (n = 8 per group) had a bilateral devascularization injury to the uterine horns. Before closure saline solution, verapamil hydrochloride (2.5 mu/kg/hour), recombinant tissue plasminogen activator (4 mg total dose), or a combination of verapamil and recombinant tissue plasminogen activator at the stated doses were instilled by means of an Alzet osmotic pump x 200 hours. Adhesion scores were evaluated after this time period by estimating the total uterine horn surface involved in adhesions at a terminal laparotomy and by clinically grading the response to determine whether minimal adhesions formed. Results of the total uterine horn surface scores were (mean score +/- SE): saline solution, 44% +/- 3.7%; verapamil, 19% +/- 4.8%; recombinant tissue plasminogen activator, 11% +/- 3.6%; combined, 3% +/- 1% (p less than 0.01 to control and p less than 0.05 to single-drug therapy). Results of the number of animals per group with minimal adhesions were as follows: saline solution, 0; verapamil, 1; recombinant tissue plasminogen activator, 3; combined, 8 (P less than 0.01). These results show a synergistic benefit of verapamil and recombinant tissue plasminogen activator to prevent postsurgical adhesion formation when delivered via the intraperitoneal route. PMID- 1903595 TI - Length vs. active force relationship in single isolated smooth muscle cells. AB - The length vs. active force relationship (L-F) may provide information about changes in smooth muscle contractile protein interactions as muscle length changes. To characterize the L-F in single toad stomach smooth muscle cells, cells were attached to a force measurement system, electrically stimulated, and isometric force and elastic modulus (an estimate of the number of attached cross bridges) determined at different cell lengths. Cells generated maximum stress (Pmax = 152.5 mN/mm2) and elastic modulus (Eact = 0.68 x 10(4) mN/mm2) at their rest length (Lcell = 78.0 microns; distance between cell attachments). At shorter lengths, active force and elastic modulus declined proportionally with active force eliminated at 0.4 Lcell. Stretching the relaxed cells up to 1.4 Lcell shifted the subsequent L-F along the length axis by the amount of the stretch but did not change Pmax or the shape of the L-F. In activated cells, force was a function of cell length rather than of shortening history. We interpret these findings as evidence that 1) Lcell is close to the optimum length for force generation, 2) the decline in force at lengths less than Lcell results from a reduced number of attached cross bridges, and 3) stretching relaxed smooth muscle cells may not move the contractile units to new positions on their L-F. PMID- 1903596 TI - Which value for the first dissociation constant of carbonic acid should be used in biological work? AB - The apparent first dissociation constant of carbonic acid has been defined in different ways in the literature. Harned and co-workers (8-10) have defined it in terms of molalities of the participating species, including H ions: Ks = mHmHCO3/mCO2. In contrast, Hastings and Sendroy have defined an apparent constant in which acidity is expressed as H ion activity: K'1 = aHmHCO3/mCO2. These constants differ by a factor gamma H, the activity coefficient of H ions at the prevailing ionic strength. Therefore, pK'1 is greater than pKs by an amount equal to -log gamma H, which, at mu = 0.16 M, is approximately 0.1. It is important that the correct value for the apparent dissociation constant or its logarithmic form be entered in the mass action expression or in the Henderson-Hasselbalch equation in order to prevent significant errors in the computation by means of these equations of quantities that cannot be directly measured. Specifically, for the derivation of bicarbonate concentration from PCO2 and pH (-log aH), pK'1 is to be used and not an uncorrected pKs. PMID- 1903598 TI - Effects of growth hormone on fuel utilization and muscle glycogen synthase activity in normal humans. AB - To examine the insulin antagonistic effects of growth hormone (GH), seven healthy subjects underwent, in random order, two 5-h euglycemic clamp studies with moderate hyperinsulinemia. A GH infusion (45 ng.kg-1.min-1) was given throughout one of the studies. GH inhibited the insulin-stimulated glucose disposal by 27% from 4.4 +/- 0.7 to 3.3 +/- 0.4 mg.kg-1.min-1 (P less than 0.02) and raised the nonprotein energy expenditures (NPEE) from 18.7 +/- 0.5 to 20.5 +/- 0.3 kcal.kg 1.24 h-1 (P less than 0.03). Lipid oxidation contributed 71.7 +/- 5.6% of NPEE during the GH infusion as compared with 48.7 +/- 5.2% during the control clamp (P less than 0.02). In skeletal muscle biopsies, insulin binding to wheat germ agglutinin-purified insulin receptors and insulin receptor kinase activity were unaffected by GH infusion. Glycogen synthase activation by insulin was inhibited by 41% during the GH clamp (fractional velocity 14.1 +/- 2.5 vs. 8.3 +/- 1.4%, P less than 0.03). In conclusion, GH 1) increases energy expenditures and inhibits glucose oxidation in favor of an increased lipid oxidation, and 2) inhibits insulin-mediated activation of the glycogen synthase in skeletal muscle biopsies by a mechanism distal to insulin receptor binding and kinase activity. PMID- 1903597 TI - Effect of exogenous and endogenous nitric oxide on mitochondrial respiration of rat hepatocytes. AB - Although nitric oxide (.N = O) biosynthesis is inducible in rat hepatocytes (HC), the physiological significance of .N = O production by these cells is unknown. Short exposure of HC to authentic .N = O led to a concentration-dependent inhibition of mitochondrial aconitase, NADH-ubiquinone oxidoreductase, and succinate-ubiquinone oxidoreductase (complexes I and II of the mitochondrial electron transport chain). Most susceptible to .N = O inhibition was mitochondrial aconitase, in which a reduction in enzyme activity to 20.2 +/- 1.6% of control was observed. In contrast to mitochondrial aconitase, cytosolic aconitase activity was not inhibited by .N = O. After exposure to a maximal inhibitory concentration of .N = O, mitochondrial aconitase activity recovered completely within 6 h. Complex I did not fully recover within this incubation period. Endogenous .N = O biosynthesis was induced in HC by a specific combination of cytokines and lipopolysaccharide. After 18 h of incubation with these stimuli, a significant inhibition of mitochondrial aconitase activity to 70.8 +/- 2.4% of controls was detected. However, this was due only in part to the action of .N = O. A non- .N = O-dependent inhibition of mitochondrial function appeared to be mediated by tumor necrosis factor. PMID- 1903599 TI - Absorption and metabolic effects of enterally administered glutamine in humans. AB - To assess absorption and metabolic effects of enterally delivered glutamine, a total of 10 healthy subjects received perfusions of natural L-glutamine at graded infusion rates (ranging from 0 to 126 mmol/h; n = 2-8 subjects at each rate) along with a nonabsorbable marker (polyethylene glycol) through a double-lumen nasojejunal tube. Perfusions were administered after an overnight fast during three consecutive 1- or 2.5-h periods and in a randomized order. In eight subjects, continuous intravenous infusion of D-[6,6-2H2]glucose, L-[1 13C]leucine, and L-[15N]alanine was simultaneously performed. Glutamine was nearly quantitatively absorbed over the 30-cm study segment; estimated Km and Vmax of glutamine absorption were 2.48 and 2.32 mmol/min over the 30-cm study segment. Enteral glutamine administration induced 1) a dose-dependent increase in plasma glutamine level; 2) a rise in the plasma level and appearance rate (Ra) of alanine (from 191 +/- 42 to 213 +/- 51 mumols.kg-1.h-1, P less than 0.05, for 0 and 46.8-mmol/h glutamine infusion rates, respectively) and in plasma levels of glutamate, citrulline, aspartate, and urea; 3) a decline in plasma free fatty acid and glycerol levels; and 4) no change in leucine or glucose Ra. We conclude that glutamine is efficiently absorbed by human jejunum in vivo and may directly inhibit lipolysis, whereas it neither affects proteolysis nor glucose production in healthy postabsorptive humans. PMID- 1903600 TI - Distribution of luminal carbonic anhydrase activity along rat inner medullary collecting duct. AB - The isolated perfused tubule technique was utilized to determine whether endogenous luminal carbonic anhydrase is present in the initial or terminal parts of the inner medullary collecting duct (IMCD) of the rat. This was accomplished by measuring the luminal disequilibrium pH in the presence of a large luminal proton source created by perfusing the lumen with a solution containing 10 mM NH4Cl. (NH3 efflux causes H+ to be released from NH+4 in the lumen). The disequilibrium pH was calculated by subtracting the equilibrium pH from the measured pH at the end of the tubule lumen. The end-luminal equilibrium pH was calculated from the total CO2 concentration in the collected fluid, as measured by microcalorimetry. The end-luminal pH was determined by measuring the fluorescent signal from the the pH-sensitive dye 2',7'-bis(2-carboxyethyl)-5(6) carboxyfluorescein (BCECF), which was added to the luminal perfusate in its nonesterified form. In the initial IMCD, there was no measurable disequilibrium pH. With the addition of the carbonic anhydrase inhibitor acetazolamide to the luminal fluid, a significant acidic pH disequilibrium was elicited. In the terminal IMCD under control conditions a statistically significant acidic disequilibrium pH was measured. The disequilibrium was obliterated when exogenous carbonic anhydrase was added to the luminal perfusate. These findings were verified by measuring total ammonia flux by ultramicrofluorometry. The results demonstrate endogenous luminal carbonic anhydrase activity in the initial IMCD but a lack of enzyme activity in the terminal IMCD. PMID- 1903601 TI - Age-related cerebrovascular reactivity to CO2 after cerebral ischemia in swine. AB - We tested the hypothesis that cerebral blood flow (CBF) reactivity to CO2 after global ischemia takes longer to recover in 1- to 2-wk-old piglets than in 6- to 10-mo-old pigs. All animals were sedated with ketamine and anesthetized with pentobarbital sodium. Cerebral ischemia was produced by sequentially tightening ligatures around the inferior vena cava and ascending aorta for 10 min. The microsphere-determined CBF response to hypercapnia (arterial PCO2 approximately 65 mmHg) was depressed at 60 min of reperfusion (9 +/- 6% of preischemia; means +/- SE) and remained depressed at 120 min (33 +/- 23% of preischemia, means +/- SE) in young pigs. In older pigs, the response was also depressed at 60 min of reperfusion (21 +/- 9% of preischemia) but was not depressed at 120 min. The pattern for recovery of hypercapnic reactivity was present in most brain regions except cerebellum, where CO2 reactivity returned to control in young animals by 120 min of reperfusion. The response to hypocapnia (arterial PCO2 approximately 25 mmHg) was also better preserved in older pigs. In older pigs recovery of CO2 reactivity during reperfusion paralleled recovery of cerebral O2 consumption over time. We conclude that older pigs have quicker return of CBF CO2 reactivity following transient global ischemia, which may be due to age-related differences in mechanisms of vascular reactivity. PMID- 1903603 TI - Metabolism of arachidonic acid in nervous system of marine mollusk Aplysia californica. AB - Studies of the marine mollusk Aplysia californica indicate that products of the 12-lipoxygenase pathway may be involved in neuronal intracellular signaling. The nervous tissue of Aplysia has a 12-lipoxygenase activity that converts both exogenous and endogenous arachidonic acid to an array of products, which include 12-hydroperoxyeicosatetraenoic acid (12-HPETE) and its metabolites hepoxilin A3, hepoxilin B3, 12-ketoeicosatetraenoic acid, and 12-oxododecatrienoic acid. These eicosanoids were identified using a combination of high-performance liquid chromatography, ultraviolet spectrometry and gas chromatography-mass spectrometry. Generation of 12-lipoxygenase products was stimulated by application of the neurotransmitters, histamine and FMRF-amide, or by stimulation of identified neural cells. In electrophysiological studies of identified L14 and sensory neurons it was found that 12-HPETE and its metabolic products exert physiological actions that resemble those of histamine and FMRF-amide. These results suggest that products of 12-HPETE metabolism may act as second messengers in Aplysia neurons. PMID- 1903602 TI - Platelet interaction with vascular smooth muscle in synthesis of prostacyclin. AB - Because vascular smooth muscle cells (SMC) can be exposed to platelets at sites of significant arterial injury, we studied whether cultured rat aorta SMC can utilize platelet-derived arachidonate and prostaglandin (PG) endoperoxides (PGG2/PGH2) in the synthesis of prostacyclin (PGI2). SMC converted exogenous PGH2 to PGI2, measured by radioimmunoassay (RIA) of 6-keto-PGF1 alpha, despite cyclooxygenase inhibition or PGH2-receptor blockade. SMC produced increasing amounts of PGI2 in the presence of an increasing number of platelets when the two cell types were coincubated with arachidonate. Furthermore, aspirin-pretreated SMC produced PGI2 in response to arachidonate, ionophore A23187, or thrombin in the presence of platelets but not in their absence. SMC, by themselves unresponsive to thrombin, produced PGI2 during coincubation with thrombin stimulated aspirin-pretreated platelets. Separation of the SMC monolayer and platelets with a filter did not prevent platelet-dependent PGI2 formation by the SMC. Finally, aspirin-pretreated SMC, in cosuspension with platelets, inhibited platelet aggregation in association with PGI2 production. These data indicate that 1) SMC can synthesize PGI2 from exogenously added PGH2 and from platelet derived arachidonate or endoperoxides, 2) direct cell-cell contact is not required for intercellular endoperoxide transfer, and 3) SMC can inhibit platelet aggregation possibly through PGI2 production from platelet-derived endoperoxides. PMID- 1903604 TI - Prostaglandin regulation of H+ secretion in amphibian epithelia. AB - The role of prostaglandins in regulating H+ excretion in amphibian epithelia was investigated. The abdominal skin of the southern leopard frog Rana pipiens and the urinary bladder of the toad Bufo marinus were used to measure proton excretion across their mucosal surface. Prostaglandin F2 alpha (PGF2 alpha) produced a dose-dependent inhibition of H+ excretion across the frog skin. Frogs pretreated with ibuprofen (30 mg.kg-1.day-1 for 3 days) showed an enhanced proton excretion similar to that observed when frogs are placed in chronic metabolic acidosis. The number of mitochondria-rich cells, the cells responsible for proton excretion, was also increased in frog skins after chronic metabolic acidosis or ibuprofen treatment. Mezerein and the phorbol ester 4 beta-phorbol 12-myristate 13-acetate (4 beta-PMA), activators of protein kinase C (PCK), decreased H+ excretion in frog skin, whereas the inactive phorbol 4 alpha-PMA was without an effect. The inhibition of proton excretion was similar to that observed with PGF2 alpha and suggested that the effects of PGF2 alpha and activation of PKC were mediated through a common pathway. Frogs pretreated with ibuprofen not only had an enhanced proton excretion rate but also had a decrease in cytosolic PKC activity. In another amphibian tissue, the toad urinary bladder, PGE2 inhibited proton excretion at low doses but enhanced H+ excretion at higher doses. Toads maintained under chronic metabolic acidosis had enhanced proton excretion rates and also had a threefold increase in cellular PGE2 concentration, which was consistent with the observation that PGE2 enhanced proton excretion at high doses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1903605 TI - Assessment of cure in schistosomiasis patients after chemotherapy with praziquantel by quantitation of circulating anodic antigen (CAA) in urine. AB - The kinetics of circulating anodic antigen (CAA) levels in urine were studied in Egyptian male patients infected with Schistosoma mansoni or with both S. mansoni and S. haematobium, before treatment, and at one, three and six weeks after chemotherapy. A quantitative enzyme-linked immunosorbent assay (ELISA) demonstrated CAA in 82% of the serum and 89% of the urine samples from these 28 patients. To evaluate the possibility of circadian variability in urine CAA levels, samples were examined in 15 patients at four intervals during a 24-hour period. No significant differences in CAA titers were observed. Seventeen patients were subsequently treated with praziquantel and followed for six weeks. CAA titers in serum and urine decreased significantly one week after therapy. Thereafter, the profile of CAA titer in urine continued to show a parallel but delayed decline compared to that in serum. While all serum CAA titers became negative three to six weeks after treatment, urine titers were negative in 47% at three weeks and 69% at six weeks. The remaining positive patients had low titers. A significant quantitative correlation in CAA titer was found between serum and urine before and after treatment. Seventeen Egyptian control subjects with no active schistosome infection were negative for CAA in both serum and urine. Our results confirm that the CAA urine assay could be used as a sensitive and non invasive method to diagnose the disease, and indicate that the assay can be used to monitor efficacy of schistosome chemotherapy. PMID- 1903606 TI - Cost-effectiveness of prophylaxis in total hip replacement. AB - A theoretical analysis was performed regarding the cost-effectiveness in terms of lives saved (reduction of fatal pulmonary embolism [PE]) and in terms of money (dollars spent for prevention and treatment) of seven strategies in the management of venous thromboembolic disease in patients over 39 years of age undergoing elective total hip replacement (THR). Strikingly, this theoretical analysis suggests that low-dose warfarin combined with clinical surveillance of deep vein thrombosis would reduce the incidence of fatal PE from 20 per 1,000 patients to 4 per 1,000 patients and simultaneously reduce the charges for venous thromboembolic disease from $550,000 to about $400,000 per 1,000 patients. Based on this analysis, we strongly recommend this measure on a routine basis. Adding venography or duplex sonography routinely to this prophylactic regimen would, in this theoretical analysis, reduce the incidence of fatal PE from 4 per 1,000 patients to 0.15 per 1,000, but adds charges of $200,000 per extra life saved in the case of routine venography and $50,000 in the case of routine sonography. Low dose warfarin prophylaxis combined with routine sonography does not generate more charges than no prophylaxis with no screening while drastically reducing the incidence of fatal PE from 20 to 0.3 per 1,000 patients. Where duplex sonography is not easily available, a 12-week postoperative course of low-dose warfarin for every patient with no routine screening will be efficacious in reducing fatal PE and as cost-effective. PMID- 1903607 TI - [The effect of fentanyl on spontaneous respiration]. AB - AIM OF THE INVESTIGATION: The effects of fentanyl on spontaneous respiration have been investigated in both animals and humans. The investigations in humans have been performed under circumstances and using methods that do not relate the results to clinical practice, e.g., predicting the effects of opioids used for postoperative pain relief on the ward. We investigated the effects of fentanyl on mechanical parameters, oxygen saturation (SAT), and end-expiratory CO2 (exCO2) in humans. METHODS: Fifteen male volunteers took part in this study, which was approved by the local ethics committee. Each received 3 micrograms/kg fentanyl intravenously after 5 min measurement of base-line values and were observed for 30 min. We continuously registered thoracic (A1) and abdominal (A2) extension and respiratory rate (RR) using piezoceramic elements. SAT, heart rate (HR), and exCO2 were measured with a pulse oximeter and infrared absorption (OSCAR, Datex). All data were transferred to a high-performance microcomputer (Multitalent, ZAK). The statistical analysis included descriptive and correlation statistics. RESULTS: After the injection of fentanyl A1, A2, RR, HR, and SAT were reduced; exCO2 increased. After a few minutes A1 increased, occasionally exceeding the base-line value. A2, RR, HR, and SAT increased without reaching base-line values. ExCO2 remained increased. The best overall correlation was found between A2 and SAT (r = 0.87). DISCUSSION: As far as comparable, our results are in accordance with those of the majority of other investigators. The difference between thoracic and abdominal extension, the latter being closely correlated with tidal volume, has not previously been described quantitatively. We attribute this result to the different innervation of the phrenic and intercostal nerves. Whereas the influence of fentanyl on SAT and exCO2 during the first 8 min can easily be explained, the varying behavior in the following minutes has not previously been described and may be due to the different binding characteristics of O2 and CO2. Alteration of the CNS setting for pCO2 may also contribute to this result. The time course of the measured parameters seems to be of clinical importance for the detection of respiratory problems in spontaneously breathing patients. PMID- 1903608 TI - Highly specific micromethod for the enzymatic determination of radioactive [14C]lactate. AB - By collecting released 14CO2 following the enzymatic decarboxylation of radiolabeled lactate, picomoles of the latter can be precisely, easily, and reproducibly measured in small biological fluids. This radioactive [14C]lactate microassay does not require a neutralization step, nor does it require chemical extractions and partioning procedures, ion exchange, or pyruvate derivatization. Under our specified conditions this simple reaction goes to completion in 90 min. Using this assay in porous adipose cells, with the cell number logarithmically less than that found in other literature methods, the measured glycolytic flux rates were consistent with those previously reported. In these studies, glycolysis was initiated with [U-14C]glucose 6-phosphate. This microradioactive lactate assay is useful when dealing with minute tissue samples and/or microliter aliquots of biological fluids. PMID- 1903609 TI - Electrotransfer of [32P]NAD allows labeling of ADP-ribosylated proteins in intact Chinese hamster ovary cells. AB - CHO-K1D cells electroporated in buffers containing [32P]NAD incorporated the label in a voltage-dependent manner. Electroporation with 650 V/cm at 1460 microF in Ham's F12 medium supplemented with 10 mM Hepes, pH 7.1, resulted in a greater than 20-fold increase in [32P]NAD uptake, while decreasing relative cellular survival by only 6%. Exposure of cells to gamma irradiation (20 Gy) prior to electroporation increased the steady-state level of poly(ADP-ribosylated) nuclear proteins two- to four-fold over that of unirradiated control cells. These data indicate that electrotransfer of [32P]NAD is a simple and rapid means of labeling the cellular NAD pool and should prove useful in the analysis of the relationship between poly(ADP-ribosylation) of nuclear proteins and DNA repair. PMID- 1903610 TI - Isolation of skeletal muscle mitochondria from hamsters using an ionic medium containing ethylenediaminetetraacetic acid and nagarse. AB - An improved procedure is reported for the isolation of skeletal muscle mitochondria from hamsters and compared with our previous method. This procedure utilizes 20 mg% Nagarse in an ionic medium containing 100 mM sucrose, 10 mM EDTA, 100 mM Tris-HCl, 46 mM KCl, and 0.5% bovine serum albumin (BSA), at pH 7.4 (medium-B). Oxidative phosphorylation was studied by measuring ADP/O ratio and respiratory control ratio (RCR) using NAD(+)-linked pyruvate-malate (PM), as well as FAD-linked succinate (SUCC) as substrates. The mitochondria isolated in medium B exhibited high RCR and high ADP phosphorylation capacity, and were superior to those prepared by our previous method. Electron micrographs of organelles isolated in medium-B revealed intact mitochondrial membrane and structural integrity, whereas those isolated with medium-A containing 50 mg% Nagarse depicted considerable damage including swelling, ruptured membrane, and loss of intramitochondrial matrix. Previously, we used a nonionic medium containing 210 mM mannitol, 70 mM sucrose, 0.1 mM EDTA, 10 mM Tris-HCl, 50 mg% Nagarse, and 0.5% BSA, at pH 7.4 (medium-A). Mitochondria isolated with medium-B yielded mean RCR values of 7.3 to 8.3 with PM, and values of 3.7 to 4.7 with SUCC as substrates, compared to 1.6 and 1.8 with PM, and 1.4 and 1.7 with SUCC for the organelles isolated using medium-A, respectively. Likewise, the ADP/O ratios were 2.6 to 2.7 with PM, and 1.6 to 1.7 with SUCC for medium-B preparations, compared to 1.5 and 1.8 with PM and 1.0 and 1.2 with SUCC for medium-A preparations, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1903611 TI - Solid-phase assay for determination of binding parameters of ligand-protein complexes with high dissociation rates. AB - The binding parameters, the affinity constant (Ka) and binding capacity (Q), of a protein possessing ligand-protein complexes with a high dissociation rate (Sex Steroid Binding protein from Bufo arenarum) were determined using a solid-phase method. The technique is based upon the adsorption of the steroid-protein complex to DEAE-cellulose. This method was compared with a nonequilibrium method (charcoal adsorption of free ligand), and the latter resulted in underestimation of both binding parameters, Ka and Q. The solid-phase method reported here is appropriate to determine the binding parameters of proteins with high dissociation rates because the results are independent of the complex half-time. The method also possesses advantages compared to other equilibrium assays such as dialysis or steady-state electrophoresis. With minor modifications, it may be useful to characterize different proteins, particularly those possessing ligand protein complexes with very high dissociation rates. PMID- 1903612 TI - Detection of peptidyl-3,4-dihydroxyphenylalanine by amino acid analysis and microsequencing techniques. AB - 3,4-Dihydroxyphenylalanine (DOPA) is an amino acid that occurs naturally in the primary sequence of many proteins and peptides. Detection of peptidyl-DOPA, however, can be elusive. This is due (i) to its coelution with leucine on most of the ion exchangers used in amino acid analysis and (ii) to the coelution of phenylthiohydantoin (PTH)-DOPA with PTH-alanine during routine C18 reversed-phase HPLC following automated Edman degradation. By application of appropriately timed temperature and/or gradient modifications during chromatography, DOPA and its PTH derivative can be adequately resolved for detection by both amino acid analysis and gas-phase sequencing. PMID- 1903613 TI - Ultrastructural and histochemical characterization of marmoset (Callithrix jacchus) Leydig cells during postnatal development. AB - Leydig cell development was investigated in the marmoset (Callithrix jacchus) testis from 24 h post partum (pp) up to sexual maturity, using ultrastructural and histochemical methods. Electron microscopically three different Leydig cell (LC) types could be distinguished: neonatal, immature and adult LCs. Neonatal LCs exhibited a round nucleus, large tubular mitochondria, abundant smooth endoplasmic reticulum (SER), and few small fat vesicles. The typical immature LCs showed a lobulated nucleus, smaller tubulo-vesicular mitochondria, less SER, and larger fat vesicles. Adult LCs contained an invaginated nucleus, tubular mitochondria, abundant SER, large fat vesicles, and lipofuscin granules. Neonatal Leydig cells occurred from 24 h pp up to 10 weeks pp, immature LCs from 2 weeks pp up to 20 weeks pp, and adult LCs from 20 weeks onwards. The appearance of a new LC population was accompanied by a numeric decrease and occurrence of regressive cells of the previous population. Developmental steps of differentiation were recognizable in the population of immature and adult LCs by the amount of SER (immature LCs), the size of mitochondria (adult LCs), and the morphology of the nucleus at the beginning of their appearance. Activity of 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) was moderate in immature LCs from 2 weeks pp to 12 weeks pp and strong in adult LCs. Neonatal LCs were not stained nor were immature LCs from 16 weeks to 20 weeks. Comparison of the ultrastructural classification of LCs and the activity of 3 beta-HSD showed that the capacity for steroid biosynthesis does not necessarily include morphological differences. Activity of non-specific esterase (nE) was found in LCs except of the period between 16 and 25 weeks pp. A transient decrease of activity was seen during the first week of life. Both, the phase of decrease and the phase of inactivity were followed by distinct activation of nE. Lipid content and the size of single fat droplets in LCs, as seen with Sudan black staining, varied during postnatal development. Finely stained granules were typical for neonatal LCs, whereas larger droplets were found in immature and adult cells. Particularly high amounts of lipids were seen at one week and between 32-60 weeks pp, which was the regression of neonatal LCs, showing ultrastructurally higher amounts of lipids than intact neonatal LCs. High amounts of lipid during puberty (32-60 weeks pp) accompanied by an activation of nE at the onset of puberty suggest an initiative role in steroidogenesis.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1903614 TI - Effects of altered PaO2 and PaCO2 on left ventricular function and coronary hemodynamics in sheep. AB - The effects of acute changes in arterial carbon dioxide and oxygen tension, produced by altering the inspired gas mixtures while maintaining constant-volume intermittent positive pressure ventilation, on global function, regional left ventricular function, and coronary hemodynamics were studied in eight sheep during halothane anesthesia. Hypercapnia (Paco2, 73.5 +/- 2.3 mm Hg, mean +/- SD) increased heart rate, stroke volume, and cardiac output but decreased systolic shortening in the base of the left ventricle. Hypocapnia (PaO2, 24 +/- 1.5 mm Hg) decreased cardiac output and coronary flow below levels seen with hypercapnia but not below levels seen with normocapnia. Systolic shortening decreased in both apical and basal regions, and left ventricular relaxation was impaired as evidenced by a reduction of the nadir of LV dP/dt. Hypoxemia (PaO2, 39 +/- 1.5 mm Hg) elicited a hyperdynamic response of the circulation, increased coronary blood flow, and exhausted the coronary flow reserve. Neither changes in PaCO2 nor changes in PaO2 caused postsystolic shortening, although hypercapnia caused nonuniformity of contraction in the left ventricle. Thus, marked alterations in oxygen and carbon dioxide tensions do not cause left ventricular dysfunction, even though moderate hypoxia reduces the coronary flow reserve. PMID- 1903615 TI - Ventilatory response to carbon dioxide after epidural clonidine injection. AB - The authors studied the effects of epidural clonidine (300 micrograms) on circulation and ventilatory control in seven healthy unpremedicated subjects. After clonidine injection, arterial blood pressure decreased significantly in all subjects (range, 13%-25% for systolic blood pressure and 13%-32% for diastolic blood pressure). Heart rate decreased significantly by 10%-16% between 75 and 105 min after injection. The slope of the ventilatory response to CO2 decreased significantly from 2.06 +/- 0.70 (baseline) to 1.37 +/- 0.68, 1.25 +/- 0.65, and 1.33 +/- 0.67 L.min-1.mm Hg-1 (mean +/- SD, P less than 0.05) at 15, 60, and 120 min. The authors conclude that epidural clonidine induces mild ventilatory and circulatory depression. PMID- 1903616 TI - Double-blind trial of pentigetide ophthalmic solution, 0.5%, compared with cromolyn sodium, 4%, ophthalmic solution for allergic conjunctivitis. AB - Fifty patients (25 per group) with the signs and symptoms of allergic conjunctivitis confirmed by positive skin test enrolled in this randomized, double-blind, parallel group, 2-week comparison of pentigetide, 0.5%, ophthalmic solution (Pentyde) and cromolyn sodium, 4%, USP ophthalmic solution (Opticrom). The physician and the patient rated the patient's overall ocular condition on days 3, 8, and 15. On day 15 both the physician and the patients rated the pentigetide group as significantly (Chi-square, P less than .05) more improved than the cromolyn sodium group. The physician rated independently conjunctival symptoms and ocular signs at days 1, 3, 8, and 15. Improvement in signs and symptoms favored pentigetide in the majority of comparisons to cromolyn sodium (14 of 18). The pentigetide group showed significantly (ANOVA, P less than .05) greater improvement in hyperemia, edema, lacrimation, and blurred vision/photophobia. Patients completed daily diaries for seven symptoms. At the end of the study, comparisons to baseline between groups favored the pentigetide group for six of the seven symptoms; for itching, improvement favored significantly (ANOVA, P less than .05) the pentigetide group. The mean severity of all symptoms decreased by 64% in the pentigetide group as compared with a decrease of 46% in the cromolyn sodium group. Adverse experiences were minor and comparable in both groups. No clinically abnormal changes were noted for visual acuity, intraocular pressure, or common laboratory tests. This double-blind, active-controlled trial demonstrates that pentigetide, 0.5%, ophthalmic solution is safe and effective in the treatment of allergic conjunctivitis. PMID- 1903617 TI - HIV-1 infection complicated by food allergy and allergic gastroenteritis: a case report. AB - A 34-year-old female with HIV-1 infection detected by positive serology in 1983 subsequently developed acute granulomatous interstitial pneumonitis, eosinophilic gastroenteritis, and angioedema associated with the ingestion of vanilla ice cream and tangerines. The enteritis and angioedema symptoms appeared to respond to large doses of oral sodium cromoglycate. Sera collected over several years before clinical symptoms revealed a sharp rise of IgE antibody in 1985 and a subsequent decline to baseline values followed by markedly increased levels of IgE antibodies to a number of inhalant and food allergens. The findings suggest disordered IgE antibody regulation as a consequence of HIV-1 infection and as a cause of allergic manifestations including eosinophilic gastroenteritis and food induced angioedema. PMID- 1903618 TI - Activation of rainbow trout complement by C-reactive protein. AB - The activation of the complement system of rainbow trout by trout C-reactive protein (CRP) was investigated. Complement fixation tests were performed by using rabbit hemolysin-sensitized sheep erythrocytes and rainbow trout complement. Purified CRP increased the consumption of complement in the presence of Streptococcus pneumoniae C-polysaccharide (CPS), indicating the activation of the complement system. In contrast to this, acute phase serum activated the complement in the absence of CPS. Consumption of the complement by acute-phase serum was depressed when CRP was removed from acute-phase serum by CPS-sepharose 4B affinity chromatography. The acute-phase serum, as well as CRP plus CPS, suppressed in vitro growth of Vibrio anguillarum in the presence of complement, and enhanced the phagocytosis of the bacteria by glass-adherent peritoneal exudate cells. These results indicated that CRP has a role in host defense during acute-phase response through the activation of the complement system, enhancement of phagocytosis, and suppression of bacterial growth. PMID- 1903619 TI - Radioimmunoassay of parathyroid hormone in cats. AB - A radioimmunoassay for measurement of midmolecule parathyroid hormone (PTH) concentration in serum from dogs was validated for use on serum from cats. The assay detected an increase in serum concentration of PTH after IV infusion of Na2 EDTA in healthy cats. Infusion of calcium chloride caused a decrease in measured PTH. Accuracy of the assay was demonstrated by quantitative recovery of a feline parathyroid gland extract added to pooled feline sera. Mean interassay and intra assay coefficients of variation were 0.13 and 0.07, respectively. Sensitivity of the assay was 0.1 ng of PTH/ml. The median PTH concentration measured in 40 adult cats was 3.5 ng/ml, with a range of 1.16 to 11.0 ng/ml. PMID- 1903620 TI - Parenteral and enteral nutrition. AB - Stress and starvation, especially when complicated by sepsis, will give rise to a rapid erosion of the cellular mass, which significantly affects morbidity and mortality. The best clinical evaluation of the nutritional state is obtained from the medical history and the physical examination. In the patient who cannot eat a balanced diet, specialized nutritional support, in the form of either enteral or parenteral nutrition, is required to prevent malnutrition in the normally nourished, or to correct the nutritional state in the malnourished. PMID- 1903621 TI - Therapy of viral infections of the central nervous system. AB - The herpesviruses (particularly HSV) are the only CNS viral infections for which reasonably clear guidelines exist for specific antiviral treatment. However, data are also beginning to emerge for specific antiviral therapy of HIV-associated CNS disease despite the lack of a clear understanding of the pathogenesis of the CNS abnormalities. As the pace of antiviral drug development increases it is likely that a wider range of CNS viral infections will be treatable in the future although entry into the CNS is likely to remain a problem limiting the successful application of many compounds to CNS infection. PMID- 1903622 TI - Structure-function studies of human interferons-alpha: enhanced activity on human and murine cells. AB - To identify functionally important regions of the human interferon (IFN)-alpha molecule, mutagenesis in vitro of human IFN-a genes was used to create analogs with deletions or specific amino acid replacements. These analogs were expressed in vitro using SP6 RNA polymerase and a rabbit reticulocyte lysate protein synthesis system. Deletion of 7 highly conserved hydrophilic amino acids from the C-terminus of human IFN-alpha 4 reduced, but did not abolish, antiviral activity on human cells. However, analogs with deletions of 15 or 25 amino acids from the C-terminus, or 28 amino acids from the N-terminus, had no measurable antiviral activity. The antiviral activity of human IFN-alpha 4 was increased by substitution of cysteine for serine at position 86, and lysine for arginine at position 121. However, other amino acid substitutions at positions 121, 122 or 123 reduced antiviral activity. The size of the side chain of the amino acid residue at position 130 was shown to be important. Replacement of the absolutely conserved leucine residue at position 131 with glutamine had little effect on antiviral activity. However, the introduction of a proline residue at this position abolished antiviral activity, probably due to the formation of a beta turn in the polypeptide chain. The antiviral activity of human IFN-alpha 4 on murine cells was increased by substitutions at positions 86, 121 and 133. This study illustrates the utility of the in vitro mutagenesis and rabbit reticulocyte lysate systems for the investigation of structure-function relationships, and extends our knowledge of the biologically active regions and species specificity of the human IFN-alpha molecule. PMID- 1903623 TI - Enhancement of murine susceptibility to oral lactate dehydrogenase-elevating virus infection by non-steroidal anti-inflammatory agents, and antagonism by misoprostol. AB - The murine lactate dehydrogenase-elevating virus (LDV) was used to study the effects of prostaglandin-acting agents on mucosal resistance to virus infection. Mice treated with non-steroidal anti-inflammatory drugs (NSAIDs) prior to oral exposure to LDV demonstrated a reduction in the mucosal barrier to LDV infection. Histological studies indicated that these NSAID effects were not a result of gross or microscopic tissue damage. The effects of two NSAIDs, indomethacin and diclofenac, were inhibited by co-treatment of mice with misoprostol, a synthetic PGE1 analog. The ability of misoprostol to modulate NSAID effects was not due to direct antiviral activity or to actions on LDV-permissive macrophages. These results show that the mammalian mucosal barrier to virus infection is prostaglandin-sensitive, and provide a model for the study of resistance to viral infection. PMID- 1903625 TI - Isolation and properties of a (1,3)-beta-D-glucanase from Ruminococcus flavefaciens. AB - A (1,3)-beta-D-glucanase [(1,3)-beta-D-glucan-3-glucanohydrolase] from Ruminococcus flavefaciens grown on milled filter paper was purified 3,700-fold (19% yield) and appeared as a single major protein and activity band upon polyacrylamide gel electrophoresis. The enzyme did not hydrolyze 1,6-beta linkages (pustulan) or 1,3-beta linkages in glucans with frequent 1,6-beta linkage branch points (scleroglucan). Curdlan and carboxymethylpachyman were hydrolyzed at 50% the rate of laminarin. The enzyme had a Km of 0.37 mg of laminarin per ml, a pH optimum of 6.8, and a temperature optimum of 55 degrees C and was stable to heating at 40 degrees C for 60 min. The molecular mass of the enzyme was estimated to be 26 kDa by gel filtration and 25 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The enzyme was completely inhibited by 1 mM Hg2+, Cu2+, and KMnO4, 75% by 1 mM Ag2+, and Ni2+, and 50% by 1 mM Mn2+ and Fe3+. In a 2-h incubation with laminaridextrins (seven to nine glucose units) or curdlan and excess enzyme, the major products were glucose (30 to 37%), laminaribiose (17 to 23%), laminaritriose (18 to 28%), laminaritetraose (13 to 21%), and small amounts of large laminarioligosaccharides. With laminarihexaose and laminaripentaose, the products were equal quantities of laminaribiose and glucose (30%) and laminaritetraose and laminaritriose (18 to 21%). Laminaribiose or laminaritriose were not hydrolyzed, indicating a requirement for at least four contiguous 1,3-beta-linked glucose units for enzyme activity. The enzyme appeared to have the properties of both an exo- and an endoglucanase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1903624 TI - Purification and partial characterization of lactacin F, a bacteriocin produced by Lactobacillus acidophilus 11088. AB - Lactacin F, a bacteriocin produced by Lactobacillus acidophilus 11088 (NCK88), was purified and characterized. Lactacin F is heat stable, proteinaceous, and inhibitory to other lactobacilli as well as Enterococcus faecalis. The bacteriocin was isolated as a floating pellet from culture supernatants brought to 35 to 40% saturation with ammonium sulfate. Native lactacin F was sized at approximately 180 kDa by gel filtration. Column fractions having lactacin F activity were examined by electron microscopy and contained micelle-like globular particles. Purification by ammonium sulfate precipitation, gel filtration, and high-performance liquid chromatography resulted in a 474-fold increase in specific activity of lactacin F. The purified bacteriocin was identified as a 2.5 kDa peptide by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS PAGE). The lactacin F peptide retained activity after extraction from SDS-PAGE gel slices, confirming the identity of the 2.5-kDa peptide. Variants of NCK88 that failed to exhibit lactacin F activity did not produce the 2.5-kDa band. Sequence analysis of purified lactacin F identified 25 N-terminal amino acids containing an arginine residue at the N terminus. Composition analysis indicates that lactacin F may contain as many as 56 amino acid residues. PMID- 1903626 TI - Identification of a new genetic determinant for cell aggregation associated with lactose plasmid transfer in Lactococcus lactis. AB - Derivatives of the lactose miniplasmid pMG820 were constructed in which a staphylococcal erm gene was inserted and in which this was accompanied by subsequent deletion of the lactose genes. The resulting plasmids were thus marked with both erythromycin resistance and lactose utilization genes in pF1132 or solely erythromycin resistance in pF1133. These plasmids retained the normal conjugation properties characteristic of lactose plasmid pLP712, including the generation by intermolecular rearrangement of high-frequency-transfer Clu+ derivatives which exhibited cell aggregation. The use of such Clu+ plasmids in a variety of mating experiments between different lactococcal strains and the observation of cell aggregation when particular mating mixtures were made led to the discovery of a new component of this conjugation system named Agg. A chromosomal gene agg was postulated to be present in some but not all strains of lactococci. High-frequency conjugation and cell aggregation thus depend on the presence of both Agg and Clu, although in a mating pair these components can be in the same or in separate strains. The Agg and Clu components may be analogous to the binding substance and aggregation substance that are involved in the hemolysin plasmid transfer system of Enterococcus faecalis, although control of their expression is different. PMID- 1903627 TI - Evaluation of hybridization characteristics of a cloned pRF106 probe for Listeria monocytogenes detection and development of a nonisotopic colony hybridization assay. AB - An internal fragment (pRF106 fragment, ca. 500 bp) of a gene (msp) coding for a 60-kDa protein of Listeria monocytogenes serotype 1/2a was used to develop a screening method to discriminate between L. monocytogenes and avirulent Listeria spp. on primary isolation plates. The L. monocytogenes-derived probe fragment of pRF106 hybridized to a 13-kb fragment of L. monocytogenes and a 3-kb fragment of one cheese isolate strain of Listeria seeligeri under stringent hybridization conditions (mean thermal denaturation temperature [Tm]-5 degrees C). The probe also hybridized to a 6-kb fragment of Listeria innocua, Listeria ivanovii, and L. seeligeri under less stringent hybridization conditions (Tm-17 degrees C). The pRF106 fragment was labeled with digoxigenin-11-dUTP and used to develop a colony hybridization assay. Colonies from lithium chloride-phenylethanol-moxalactam agar were blotted onto nylon membranes. The cells were pretreated with microwaves before lysis with sodium hydroxide. DNA-DNA hybridization and posthybridization washing were done at high stringency (Tm-7 degrees C). The nonisotopic colony hybridization procedure was specific for L. monocytogenes when evaluated against pure cultures of L. monocytogenes and other Listeria species, excluding the cheese isolate of L. seeligeri. Also, it was specific for L. monocytogenes when evaluated with Listeria-negative food enrichment cultures that were inoculated in the laboratory with Listeria species. PMID- 1903628 TI - Aerobic biodegradation potential of subsurface microorganisms from a jet fuel contaminated aquifer. AB - In 1975, a leak of 83,000 gallons (314,189 liters) of jet fuel (JP-4) contaminated a shallow water-table aquifer near North Charleston, S.C. Laboratory experiments were conducted with contaminated sediments to assess the aerobic biodegradation potential of the in situ microbial community. Sediments were incubated with 14C-labeled organic compounds, and the evolution of 14CO2 was measured over time. Gas chromatographic analyses were used to monitor CO2 production and O2 consumption under aerobic conditions. Results indicated that the microbes from contaminated sediments remained active despite the potentially toxic effects of JP-4. 14CO2 was measured from [14C]glucose respiration in unamended and nitrate-amended samples after 1 day of incubation. Total [14C]glucose metabolism was greater in 1 mM nitrate-amended than in unamended samples because of increased cellular incorporation of 14C label. [14C]benzene and [14C]toluene were not significantly respired after 3 months of incubation. With the addition of 1 mM NO3, CO2 production measured by gas chromatographic analysis increased linearly during 2 months of incubation at a rate of 0.099 mumol g-1 (dry weight) day-1 while oxygen concentration decreased at a rate of 0.124 mumol g-1 (dry weight) day-1. With no added nitrate, CO2 production was not different from that in metabolically inhibited control vials. From the examination of selected components of JP-4, the n-alkane hexane appeared to be degraded as opposed to the branched alkanes of similar molecular weight. The results suggest that the in situ microbial community is active despite the JP-4 jet fuel contamination and that biodegradation may be compound specific.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1903629 TI - Interleukin 1 alpha, tumor necrosis factor alpha, and interferon gamma in psoriasis. AB - Although recent studies have suggested that a variety of cytokines released by keratinocytes and inflammatory leukocytes could contribute to induction or persistence of the inflammatory processes in psoriasis, it remains unclear how production of these cytokines is regulated in psoriatic patients. To elucidate the biologic relevance of these cytokines to the pathogenesis of psoriasis, we investigated serum levels of interleukin 1 alpha, tumor necrosis factor alpha, and interferon gamma in 21 patients with psoriasis vulgaris, together with 21 healthy controls. The mean serum levels of interleukin 1 alpha and tumor necrosis factor alpha were not significantly different from those in controls, while those of interferon gamma were significantly elevated in the patients with psoriasis. Serum levels of interleukin 1 alpha correlated negatively with clinical disease severity expressed as psoriasis area and severity index score and with duration of psoriasis. In contrast, interferon gamma levels were related, although not significantly, to disease severity. In addition, an inverse correlation was noted between the interleukin 1 alpha levels and interferon gamma levels. These results indicate that interleukin 1 alpha and interferon gamma may be relevant to the induction and perpetuation, respectively, of the inflammatory responses in psoriasis, and that these cytokines, which have similar biologic properties, may strictly regulate one another's production in vivo. PMID- 1903631 TI - Oesophageal intramural pseudodiverticulosis--always benign? AB - Oesophageal intramural pseudodiverticulosis is a rare condition that presents with dysphagia. The diagnosis is usually not apparent endoscopically and careful radiological evaluation is required. Previous reports suggest a benign course with good response of dysphagia to oesophageal dilatation and complications have not been described. Two cases are reported, one in whom life threatening haemorrhage developed following dilatation, and one complicated by a retro oesophageal collection. It is possible that oesophageal intramural pseudodiverticulosis results in an increased propensity to trauma and even perforation. PMID- 1903630 TI - Semen characteristics and diabetes mellitus: significance of insulin in male infertility. AB - A study was made of semen quality and serum hormonal profiles (FSH, LH, prolactin, testosterone) of patients with type I diabetes mellitus. Semen parameters and levels of prolactin and testosterone were significantly altered in the diabetic state. The concentration of insulin in serum and seminal plasma and the serum levels of FSH, LH, and testosterone were measured in 80 men classified in the following groups: fertile subjects, infertile normoglycemic subjects, subjects with carbohydrate intolerance, and excretory and secretory azoospermic subjects. In all groups, seminal insulin concentrations were higher than those obtained in serum. The hormone appears to freely cross the blood-testis barrier, there to be concentrated in the semen. The levels of insulin in serum and seminal plasma did not correlate with semen parameters and are not suitable markers of seminal quality. For unknown reasons, the concentrations of insulin in seminal plasma were lower in the subjects suffering from carbohydrate intolerance. PMID- 1903632 TI - [Laryngeal obstruction due to familial Recklinghausen's disease]. AB - A case of familial multiple neurofibromatosis with laryngeal involvement is described. The patient required surgical treatment because of rapid tumour growth associated with dyspnoea, dysphonia and dysphagia. Whereas the extensive growth prevented entire removal of all tumour lumps, endolaryngeal microsurgery resulted in an important improvement of laryngeal symptoms and of the quality of life. PMID- 1903633 TI - Improved portal film image quality in radiation therapy with high energy photons. AB - Various metal screen-film combinations have been investigated in order to determine the best radiographic image. The quality of these different combinations has been evaluated by measuring the scattered to primary film dose ratio S/P. The S/P ratio increases with increasing atomic number of the front screen for 4 MV x-rays but shows no significant difference for 8 MV x-rays. For rear screens the S/P ratio is slightly increased for higher atomic numbers. A metal with an atomic number around 26-29 should be an optimal metal screen regarding quality aspects. A cassette of stainless steel has, in clinical use for portal and/or verification films, given very good images. PMID- 1903634 TI - Neurofibromatosis: an unusual oral manifestation. PMID- 1903635 TI - Gi-2 is at the centre of an active phosphorylation/dephosphorylation cycle in hepatocytes: the fine-tuning of stimulatory and inhibitory inputs into adenylate cyclase in normal and diabetic states. PMID- 1903636 TI - The differentiating agent, retinoic acid, causes an early inhibition of inositol lipid-specific phospholipase C activity in HL-60 cells. AB - Retinoic acid, a derivative of vitamin A, is shown to inhibit the levels of inositol phosphates and diacylglycerol by 25-30% when added to intact HL-60 cells at concentrations which induce differentiation. The onset of inhibition occurs after 10 min and reaches a maximum at 45 min. To study the mechanism and the site of action of retinoic acid, the activity of the phosphatidylinositol bisphosphate specific phospholipase C was studied in cells permeabilized with streptolysin O and in membrane preparations. Phospholipase C activity was stimulated either via the guanine nucleotide regulatory protein (G-protein) or directly by Ca2+. Retinoic acid treatment, in a time- and concentration-dependent manner, led to a decrease in phospholipase C activity when stimulated with either GTP gamma S or NaF, both of which activate the enzyme via the G-protein. By contrast, it had no effect on the enzyme activity when stimulated with Ca2+ alone. This indicates that retinoic acid interferes with the coupling of the G-protein and phospholipase C. A relationship between the inhibition of phospholipase C activity and the induction of differentiation by retinoic acid was investigated. Only a small inhibition of GTP gamma S-stimulated phospholipase C activity was observed when an analogue of retinoic acid, etretine or Ro10-1670, with low differentiating activity, was used. Moreover, no inhibition of the GTP gamma S stimulated phospholipase C activity was observed in an HL-60 sub-line resistant to retinoic acid. These results suggest that phospholipase C inhibition is an important step in the induction of differentiation. PMID- 1903637 TI - Involvement of cellular calcium incorporated from the medium in production of inositol trisphosphate in A-431 cells. AB - The property of intensive 45Ca2+ uptake by A-431 human epidermoidal carcinoma cells was indicated to be an influx, not binding to the cell surface, since the two apparent dissociation constants (Kd) between 45Ca2+ and cells were almost the same when measured in either the presence or absence of 1 mM [ethylenebis (oxyethylenenitrilo)]tetraacetic acid (EGTA); these constants were approximately 5-10 x 10(-6) and 1 x 10(-4) M, respectively, which are much higher than the chelating constant of EGTA for Ca2+ (approximately 10(-11) M). Furthermore, addition of A23187, a calcium ionophore, rapidly released the 45Ca2+ incorporated into cells at both 37 degrees C and 0 degrees C. The 45Ca2+ associated with the cells was slowly released or exchanged when cells were incubated in medium depleted of Ca2+, or in that containing 1 mM non-radioactive Ca2+. The ability of A-431 cells to respond to extracellular ATP by elevating their level of intracellular calcium ions, as well as by producing inositol trisphosphate (InsP3), was suppressed in cells depleted of cellular calcium. These data suggest that calcium ions are extensively incorporated or exchanged with those outside the cells, maintained as stored calcium, and involved in production of InsP3, when A-431 cells are stimulated by ATP to trigger the signal transduction system. PMID- 1903639 TI - Sponsorship: corporate concerns. PMID- 1903638 TI - History of nursing. Coming full circle. PMID- 1903640 TI - Forging an agreement. PMID- 1903641 TI - North of England focus. Golden opportunities. Interview by Charlotte Alderman. PMID- 1903642 TI - Management of vaginal dryness. PMID- 1903643 TI - Attitudes to old people: a review. Part 2. PMID- 1903644 TI - Learning difficulties and communication. PMID- 1903645 TI - A nurse recalls how euthanasia brought her father a peaceful death. PMID- 1903646 TI - Do nurses have ethics? PMID- 1903647 TI - Research in nursing: research for a star? PMID- 1903648 TI - Health promotion: health visiting in the field. PMID- 1903649 TI - Working parents: six months' labour. PMID- 1903650 TI - Special job focus. PMID- 1903651 TI - [Nutrition in mucoviscidosis]. PMID- 1903652 TI - Demonstration of a functional requirement for the carbamate nitrogen of ribulosebisphosphate carboxylase/oxygenase by chemical rescue. AB - Ribulosebisphosphate carboxylase/oxygenase is reversibly activated by the reaction of CO2 with a specific lysyl residue (Lys191 of the Rhodospirillum rubrum enzyme) to form a carbamate that coordinates an essential Mg2+ cation. Surprisingly, the Lys191----Cys mutant protein, in the presence of CO2 and Mg2+, exhibits tight binding of the reaction intermediate analogue 2-carboxyarabinitol bisphosphate [Smith, H. B., Larimer, F. W., & Hartman, F. C. (1988) Biochem. Biophys. Res. Commun. 152, 579-584], a property normally equated with effective coordination of the Mg2+ by the carbamate. Catalytic ineptness of the Cys191 mutant protein, despite its ability to coordinate Mg2+ properly, might be due to the absence of the carbamate nitrogen. To investigate this possibility, we have evaluated the ability of exogenous amines to restore catalytic activity to the mutant protein. Significantly, the Cys191 protein manifests ribulose bisphosphate dependent fixation of 14CO2 when incubated with aminomethanesulfonate but not ethanesulfonate. This novel activity reflects a Km value for ribulose bisphosphate which is not markedly perturbed relative to wild-type enzyme, a Km for Mg2+ which is in fact decreased 10-fold, and rate saturation with respect to aminomethanesulfonate (Kd = 8 mM). Chromatographic and spectrophotometric analyses reveal the product of CO2 fixation to be D-3-phosphoglycerate, while turnover of [1-3H]ribulose bisphosphate into [3H]phosphoglycolate confirms oxygenase activity. We conclude that aminomethanesulfonate restored ribulosebisphosphate carboxylase/oxygenase activities to the Cys191 mutant protein by providing a nitrogenous function which satisfies a catalytic demand normally met by the carbamate nitrogen of Lys191. PMID- 1903653 TI - Site-directed mutagenesis of the psbC gene of photosystem II: isolation and functional characterization of CP43-less photosystem II core complexes. AB - Two mutants of Synechocystis PCC 6803 lacking the psbC gene product CP43 were constructed by site-directed mutagenesis. Analysis of cells and thylakoid membranes of these mutants indicates that PS II reaction centers accumulate to a concentration of about 10% of that of WT cells. PS II core complexes isolated from mutants lacking the CP43 subunit show light-driven electron transfer from the secondary electron donor Z to the primary quinone electron acceptor QA with a quantum yield similar to that of wild type, indicating that CP43 is not required for binding or function of QA. The use of mutants for the removal of CP43 thus avoids the loss of QA function associated with biochemical extraction of CP43 from intact core complexes. Both absorbance and fluorescence emission maxima of the mutant complexes show a blue shift in comparison to the WT PS II core complex, indicating that the absorbance spectrum of CP43 is red-shifted relative to that of the remainder of the core complex. The antenna size of these CP43-less complexes is about 70% of that of WT, indicating that approximately 15 chlorophyll molecules are bound by CP43. The molecular mass of the PS II complex, including the detergent shell, shifts from 310 +/- 15 kDa in WT to 285 +/- 15 kDa in the CP43-less mutants. PMID- 1903654 TI - Molecular cloning and primary structure of rat thyroxine-binding globulin. AB - Rat thyroxine-binding globulin (TBG) cDNAs were isolated from a rat liver cDNA library by using a human TBG cDNA as a probe. From two overlapping cDNA inserts, an aligned cDNA sequence of 1714 nucleotides was obtained. There was 70% homology with human TBG cDNA over the span of 1526 nucleotides. In order to confirm that the cloned cDNA encodes rat TBG and to localize the NH2-terminal amino acid of the mature molecule, the protein was purified by affinity chromatography and subjected to direct protein microsequencing. The NH2-terminal amino acid sequence was identical with that deduced from the nucleotide sequence. The rat TBG cDNA sequenced consisted of a truncated leader sequence (35 nucleotides), the complete sequence encoding the mature protein (1194 nucleotides) and the 3'-untranslated region (485 nucleotides), containing two polyadenylation signals. It was deduced that rat TBG consists of 398 amino acids (Mr = 44,607), three NH2-terminal residues more than human TBG, with which it shares 76% homology in primary structure. Of the six potential N-glycosylation sites, four are located in conserved positions compared to human TBG. Northern blot analysis of rat liver revealed an approximately 1.8-kilobase TBG mRNA. Its amount increased markedly following thyroidectomy and decreased with thyroxine treatment in a dose dependent manner. PMID- 1903655 TI - Protein kinase C in tumoricidal activation of mouse macrophage cell lines. AB - A potential role of protein kinase C (PKC) in lipopolysaccharide- (LPS-) induced tumoricidal activation of macrophages was investigated by using two mouse macrophage cell lines (P388D1 and J774). J774 cells are stimulated by LPS to kill target P815 mastocytoma cells, whereas P388D1 cells fail to develop such an ability. Pretreatment of J774 cells with H-7 or phorbol myristate acetate resulted in a significant inhibition of LPS-induced cytotoxicity, whereas pretreatment with H-8, ML-7, HA1004, or W-7 did not. Since these results suggested a critical role of PKC in the activation process, the properties of PKC in the two cell lines were compared. Western blotting with rabbit antiserum specific for the PKC beta regulatory domain allowed detection of a protein of 79 kilodaltons (kDa) in the detergent lysates of both cell lines that were not stimulated by LPS. However, LPS treatment resulted in the appearance of a second protein of 40 kDa only in J774 cells and not in P388D1 cells. Furthermore, two forms of protein kinase (one basic and the other acidic) were identified in the cytosol of J774 cells by HPLC on DEAE-5PW, whereas only the basic form was found in P388D1 cells. On the basis of the response of the basic and acidic form protein kinases to phosphatidylserine (PS), diolein, and Ca2+, the basic form was found to contain both regulatory and catalytic domains of PKC, whereas the acidic form was suggested to represent the PKC catalytic domain.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1903656 TI - Biosynthesis of the cloned intestinal Na+/glucose cotransporter. AB - The initial stages in the biosynthesis of the cloned Na+/glucose cotransporter were examined by in vitro expression of the protein in the absence and presence of pancreatic microsomes. Glycosylation was detected by endoglycosidase-H shifts in the apparent size of the proteins on SDS-PAGE. In the presence of microsomes, Mr increased from 52,000 to 58,000, and this was reversed by endo-H. This demonstrates that the protein is glycosylated and that there is no large cleavable signal sequence. Using partial transcripts and site-directed mutagenesis, we established that Asn-248 is glycosylated. Glycosylation was not required for the functional expression of the transporter in Xenopus oocytes. In terms of the topology of the protein, these results suggest that Asn-248 is on the external surface of the membrane. PMID- 1903657 TI - Prostaglandin endoperoxide synthase: regulation of enzyme expression. PMID- 1903658 TI - Distribution of apolipoprotein E between free and A-II complexed forms in very low- and high-density lipoproteins: functional implications. AB - The stability of apolipoprotein E/lipoprotein associations has been examined as a function of apolipoprotein E phenotype. Visualisation by immunoblotting showed plasma apolipoprotein E to be present in two forms; the free form and, as previously described, an E-A-II complex. In very low density lipoproteins isolated by gel filtration from subjects with E3/3 and E4/3 phenotypes, apolipoprotein E was present essentially in the free form (ratio free: complex of 12.2 and 37.5, respectively). Exploiting ultracentrifugation as the disruptive agent, very-low-density lipoproteins thus isolated were shown to have substantially lower ratios (5.6 and 5.4, respectively) reflecting preferential loss of free apolipoprotein E. In high-density lipoproteins isolated by gel filtration from E3/3 phenotypes, apolipoprotein E was largely present as an E-A II complex (80.3%). In contrast, the majority of apolipoprotein E in high-density lipoproteins from E4/3 phenotypes was present in the free form (58.7%). In both phenotypes, the content of free apolipoprotein E was markedly reduced by ultracentrifugation. The results confirm the notion that the formation of the E-A II complex is a major determinant of the stability of apolipoprotein E-high density lipoprotein associations. Moreover, that the predominant, ancestral isoform, apolipoprotein E3, exists largely as an E-A-II complex in higher density lipoproteins has important functional implications for this plasma source of apolipoprotein E. PMID- 1903659 TI - Soybean lipoxygenase catalysed oxygenation of unsaturated fatty acid encapsulated in cyclodextrin. AB - The linoleic or arachidonic acid entrapped in cyclodextrin (alpha, beta or gamma) serves as an excellent substrate for soybean lipoxygenase-1 catalysis. At pH 9.0 the Km values for the beta-cyclodextrin encapsulated arachidonic acid, referred herein as encapsulated substrate, and the Tween-20 dispersed substrate were 7.7 microM and 7.5 microM, respectively. However, the Vmax values for alpha- and beta cyclodextrin solubilized substrates were lower in comparison with the Tween-20 dispersed substrate. Interestingly, the pH-activity profile for the enzyme towards cyclodextrin encapsulated arachidonic acid showed optimum around 7.5, while that towards Tween-20 dispersion showed the expected broad optimum in the alkaline range (8.5-10.0). The activity with encapsulated substrate at pH 7.5 was at least 5-fold higher than that obtained with Tween-20 dispersed substrate at the corresponding pH. Similar results were obtained using linoleic acid. The second order rate constant, Kcat/Km, for the encapsulated substrate was an order of magnitude higher when compared to the Tween-20 dispersed substrate. The plot of v obtained at pH 9.0, against S gave hyperbolic curves for both the encapsulated as well as the Tween-20 dispersed substrates, whereas at pH 7.5, the curve for cyclodextrin encapsulated arachidonic acid appeared initially concave and then at higher concentrations of the substrate sigmoidal. The positional specificity of soybean lipoxygenase remained unaltered, however. PMID- 1903660 TI - Skin conductance activity after intraventricular administration of 6-hydroxydopa in rats. AB - Absence of skin conductance response (SCR) and failure of its habituation are psychophysiological signs observed in most schizophrenics. In the present experiments, skin conductance activity was studied in rats before and after intraventricular administration of 6-hydroxydopa (6-OHdopa), a neurotoxin that selectively destroys noradrenaline nerve terminals and induces denervation supersensitivity at the synapse. All intact rats studied (n = 32) showed SCR and its habituation to repeated auditory stimuli (500 Hz, 90 dB, 1 sec, 20 times). They also showed some spontaneous fluctuation (SF) of the skin conductance. In the early stage following the 6-OHdopa (100 micrograms) administration (n = 16), it was noted that the SCR disappeared and the SF were markedly reduced in frequency (p less than 0.001). From the third day to the fourth week after this treatment, there was some recovery of the SF rate, and the SCR tended to reappear with a marked slowing down of its habituation. Eight weeks after the treatment, the majority (11/16) of the 6-OHdopa rats showed habituation failure of the SCR (p less than 0.005); vehicle-treated rats (n = 16) did not show these alterations. Estimation of catecholamine concentration after the experiment confirmed the selective depletion of brain noradrenaline. These results suggest that destruction of the noradrenergic fibers after the 6-OHdopa treatment and denervation supersensitivity which developed later are the cause of the nonresponding and nonhabituating changes of SCR, respectively. PMID- 1903661 TI - Somatosensory evoked potentials as indicators of altered cerebral excitability during psychotropic drug treatment. AB - We observed an increase in the amplitude of the early cortical somatosensory evoked potentials (SSEPs) in five patients who developed myoclonus and/or generalized seizures during treatment with antidepressants. The increases correlated closely with the course of the clinical disturbances. In every case the SSEPs returned to normal values after the discontinuation of the psychotropic drugs. We suggest that SSEPs might help to identify and monitor patients who are at an increased risk of potentially hazardous side effects during psychopharmacological treatment. PMID- 1903662 TI - The bcl-2 gene and protein in malignant lymphomas. AB - The 14;18 chromosomal translocation, characteristic of a significant fraction of non-Hodgkin's lymphomas, results from an apparent error in immunoglobulin gene rearrangement. Breakpoints for the 14;18 translocation cluster at defined sites on chromosomes 14 and 18 and this clustering has important implications for molecular diagnostic studies of lymphomas. The major effect of the 14;18 translocation is a transcriptional deregulation of the bcl-2 gene resulting in levels of the protein and mRNA that appear to be inappropriate for B cells at a comparable stage of differentiation. Gene transfer studies have demonstrated that inappropriate bcl-2 expression has subtle effects on cellular growth and survival without overt tumorigenic conversion. Biochemical studies have shown that bcl-2 is an integral membrane protein localized to the cytoplasmic side of cellular membranes, suggestive of a role in signal transduction, but no demonstrable biochemical activity has been reproducibly associated with the protein. PMID- 1903663 TI - High energy neutron treatment for pelvic cancers: study stopped because of increased mortality. AB - OBJECTIVE: To compare high energy fast neutron treatment with conventional megavoltage x ray treatment in the management of locally advanced pelvic carcinomas (of the cervix, bladder, prostate, and rectum). DESIGN: Randomised study from February 1986; randomisation to neutron treatment or photon treatment was unstratified and in the ratio of 3 to 1 until January 1988, when randomisation was in the ratio 1 to 1 and stratified by site of tumour. SETTING: Mersey regional radiotherapy centre at Clatterbridge Hospital, Wirral. PATIENTS: 151 patients with locally advanced, non-metastatic pelvic cancer (27 cervical, 69 of the bladder, seven prostatic, and 48 of the rectum). INTERVENTION: Randomisation to neutron treatment was stopped in February 1990. MAIN OUTCOME MEASURES: Patient survival and causes of death in relation to the development of metastatic disease and treatment related morbidity. RESULTS: In the first phase of the trial 42 patients were randomised to neutron treatment and 14 to photon treatment, and in the second phase 48 to neutron treatment and 47 to photon treatment. The relative risk of mortality for photons compared with neutrons was 0.66 (95% confidence interval 0.40 to 1.10) after adjustment for site of tumour and other important prognostic factors. Short term and long term complications were similar in both groups. CONCLUSIONS: The trial was stopped because of the increased mortality in patients with cancer of the cervix, bladder, or rectum treated with neutrons. PMID- 1903664 TI - Allergy to penicillin: fable or fact? AB - OBJECTIVE: To assess whether, on the basis of one blood test, penicillin allergy might be excluded sufficiently for general practitioners to give oral penicillin to patients claiming a history of penicillin allergy. DESIGN: Prospective study of patients referred by general practitioners. SETTING: Outpatient allergy clinic in a district general hospital. PATIENTS: 175 referred patients who gave a history of immediate type reaction to penicillin, of whom 144 attended as requested and 132 completed the investigations. MAIN OUTCOME MEASURES: History and examination, serum radioallergosorbent test to phenoxymethylpenicillin and benzylpenicillin, and oral challenge with penicillin. RESULTS: Of 132 patients, four were confirmed to have penicillin allergy by the radioallergosorbent test and 128 had an oral penicillin challenge without ill effect. CONCLUSIONS: Most patients who gave a history of penicillin allergy are not so allergic, and their actual allergic state should be substantiated whenever feasible. For patients reporting minor or vague reactions negative findings with a radioallergosorbent test to phenoxymethylpenicillin and benzylpenicillin provide sufficient evidence to give oral penicillin safely. PMID- 1903665 TI - Setting standards for long term care of the elderly in hospital. PMID- 1903666 TI - Prophylactic lithium in puerperal psychosis. The experience of three centres. AB - At three centres, 21 women at high risk for puerperal psychosis were given prophylactic lithium carbonate late in the third trimester of pregnancy or immediately after delivery. Only two of the women had a recurrence of their psychotic illness while on prophylactic lithium. One woman given lithium during third trimester had an unexplained stillbirth. Although a larger sample in a carefully controlled study is still required, there now seems to be grounds for the use of prophylactic lithium immediately after delivery in women not breastfeeding who have previously suffered from either puerperal psychosis or bipolar disorder. PMID- 1903668 TI - Deprenyl: protective vs. symptomatic effect. PMID- 1903667 TI - The Scottish survey of old long-stay in-patients. AB - A total of 2605 old long-stay patients, defined as those admitted to hospital before the age of 65 years and in hospital more than six years, were identified in psychiatric hospitals serving 83% of the Scottish population. The bed occupancy was 59 per 100,000 of the general population, with a range among hospitals of 19-123 per 100,000. Of all patients, 64% were schizophrenic and 15% had organic brain disease; most patients were male, single and over 60 years of age; 41% had been in hospital more than 30 years; 61% had either florid psychotic symptoms or symptoms of a deficit state in marked or severe degree, and the rehabilitation potential for 70% was low. An increasing prevalence of deficit symptoms in schizophrenics was associated with increasing length of stay in hospital; the difference was most marked between those admitted before and after 1953. PMID- 1903669 TI - Deprenyl: the exciting possibility of protective effect. PMID- 1903670 TI - Cytogenetic evaluation of four canine mast cell tumors. AB - We evaluated four canine cutaneous mast cell tumors cytogenetically. All four tumors contained both hypodiploid and hyperdiploid cells, an increase in the number of metacentric chromosomes, exchange configurations, and cells showing loss of an X chromosome. All tumors contained metaphases with chromosome gaps and breaks at frequencies greater than observed spontaneous chromosome breaks in normal cultured canine peripheral blood lymphocytes. Three of the four tumors had a normal modal chromosome number of 78. The fourth tumor had a modal chromosome number of 93, which represented 15% of the cells evaluated from this tumor. PMID- 1903671 TI - Translocation (14;19) in acute biphenotypic leukemia. AB - Translocation (14;19)(q32;q13.1) is an acquired chromosomal rearrangement that has been associated with chronic lymphocytic leukemia of B-cell phenotype frequently progressing to lymphoma. Molecular analysis suggests that the translocation involves the immunoglobulin heavy chain gene on chromosome 14 and the BCL3 oncogene on chromosome 19. We present the first case of t(14;19) in a patient with acute leukemia. Correlation of detailed cytogenetic and molecular genetic studies, cell surface marker analysis, cytochemistry, and electron microscopy indicated that the leukemic cells were biophenotypic, with characteristics consistent with both myeloid and B-lineage lymphoid differentiation. PMID- 1903672 TI - Immobilisation of beta-D-galactosidase from Escherichia coli on cellulose beads and its use for the synthesis of disaccharide derivatives. AB - beta-D-Galactosidase, isolated from cloned E. coli, was immobilised on cellulose beads via oxidation with sodium periodate, activation by cyanuric chloride, or diazotisation. beta-D-Galactosidase immobilised via azo bonds showed the highest relative activity and thermostability, and was used for synthesis of disaccharide methyl glycosides. PMID- 1903673 TI - Soluble interleukin-2 receptor and soluble CD8 antigen levels in serum from patients with non-resectable lung cancer. AB - In a preliminary longitudinal study two women with histologically verified adenocarcinoma of the lung, without simultaneous infectious or inflammatory conditions, were seen every 2 weeks until death. In one of the patients serum soluble interleukin-2 receptor (sIL-2R) levels rose progressively while the levels for the other patient increased during the second half of the observation period. Serum soluble CD8 antigen (sCD8 Ag) showed a pattern dissimilar to the one for sIL-2R. In a retrospective cross-sectional study circulating levels of sIL-2R and sCD8 Ag were measured before explorative thoracotomy in a total of 65 patients with histologically proven non-resectable carcinoma of the lung. The sIL 2R levels were significantly increased independently of histological subclassification while sCD8 Ag was increased only in patients with small-cell lung cancer. There was no correlation between pre-operative values and length of survival. PMID- 1903674 TI - Restoration of high immunoglobulin gene expression in chronic lymphoid leukemia: a possible application for gene therapy. AB - In this study, using interleukin-2 and gamma interferon, we first induced the differentiation into plasma cells of primary chronic lymphoid leukemic B cells from patients whose T cells failed to produce interleukin-2. We next demonstrated that these malignant primary B lymphocytes (i.e., lymphocytes which have not been subjected to any procedure aiming at their immortalization or their transformation into cell lines) functionally expressed transfected genes under the control of exogeneous Ig promoters and enhancers during their terminal differentiation into plasma cells. We discussed the possibility of applying this approach to gene therapy to correct this type of lymphocytic leukemia in man. PMID- 1903676 TI - Travel advisory for travellers to the Persian Gulf (as of 7 March, 1991). PMID- 1903675 TI - The superantigen Pseudomonas exotoxin A requires additional functions from accessory cells for T lymphocyte proliferation. AB - We have examined the functions required of accessory cells (AC) for murine thymocyte proliferation induced by Pseudomonas exotoxin A (PE) and have compared these functions to those required of a known superantigen, staphylococcal enterotoxin B (SEB). We demonstrate that PE, like SEB, preferentially stimulates PNA+ thymocytes expressing a specific V beta element within the T cell receptor. However, PE requires functions from AC that are distinct from those required by SEB. AC treated with paraformaldehyde (PCHO) prior to stimulation supported thymocyte proliferation induced by SEB but not PE. However, when AC were treated with PCHO subsequent to stimulation with PE, thymocyte proliferation was observed, which suggests that PE requires antigen processing in addition to presentation. Furthermore, treatment of AC with lysosomotropic agents abrogated thymocyte proliferation induced by PE but not SEB. Antibodies to MHC class II molecules inhibited thymocyte proliferation induced by both PE and SEB. In addition, we observed that interleukin 1 alpha (IL-1 alpha) participated in the proliferation of thymocytes induced by PE but not SEB. Thus, our data indicate that PE is a unique microbial superantigen that requires additional AC functions for T lymphocyte proliferation. PMID- 1903677 TI - Status of penicillinase-producing Neisseria gonorrhoeae in Canada--1989. PMID- 1903679 TI - Depression of endothelium-dependent relaxation in aorta from rats with Brugia pahangi lymphatic filariasis. AB - A role for altered endothelial cell function is emerging in the pathogenesis of disease. We have previously demonstrated that Dirofilaria immitis, the canine heartworm, depresses endothelium-dependent responses and alters the mechanism of relaxation in the in vivo femoral artery of infected dogs. Exposure of rat aorta to the parasite or parasite-conditioned medium selectively depresses endothelium dependent relaxation. D. immitis is closely related to the major human filarial pathogens. This study was designed to examine the effect of chronic infection with the filarial nematode Brugia pahangi on endothelium-mediated responses of the rat aorta in vitro. We tested the hypothesis that endothelium-dependent responses are depressed in the aorta from rats infected with B. pahangi. Rings of thoracic and abdominal aorta were suspended in muscle baths for measurement of isometric tension. Dose-response relations to norepinephrine, endothelium dependent dilators (acetylcholine, histamine, and A23187), and nitroglycerin were done. In some experiments, inhibitors of cyclooxygenase (indomethacin and aspirin), guanylate cyclase (methylene blue), and nitric oxide formation (N-nitro L-arginine methyl ester; L-NOARG) were used. No differences in vascular reactivity were detected in the thoracic aorta. In contrast, endothelium dependent responses in abdominal aorta of Brugia-infected rats were significantly depressed when compared with control aorta from noninfected rats. Acetylcholine relaxation was further depressed by indomethacin and aspirin. After L-NOARG, acetylcholine relaxation in control abdominal aorta was completely abolished; however, in abdominal aorta of Brugia-infected rats, acetylcholine still caused relaxation. Methylene blue inhibited acetylcholine relaxation in both control and Brugia-infected abdominal aorta; however, relaxation in Brugia-infected aorta was significantly greater than control. This study demonstrates that endothelium dependent relaxation can be altered by chronic experimental filarial infection in the absence of direct contact between the blood vessel and the parasite. The mechanism of relaxation in the Brugia-infected abdominal aorta appears to be altered when compared with control, suggesting that parasites are capable of modulating vascular reactivity by inducing changes in endothelial cell behavior. The mechanism may involve parasite-induced local inflammation or alterations in endothelial cell metabolism. Understanding how chronic experimental filarial infection alters vascular reactivity may enhance our understanding of the pathogenesis of human filariasis. PMID- 1903680 TI - Hirudin and nitrates inhibit the thrombin-induced release of endothelin from the intact porcine aorta. AB - In intact porcine aorta, endothelium-derived nitric oxide released on thrombin stimulation inhibits the concomitant production of endothelin. Experiments were designed to examine the effect of hirudin (which inactivates thrombin) and the nitrovasodilators nitroglycerin and 3-morpholinosydnonimine on the spontaneous and thrombin-stimulated release of endothelin in intact blood vessels. Endothelin was detected by radioimmunoassay in the incubating medium of intact porcine aortas with endothelium. The spontaneous release of endothelin was not affected by hirudin (0.1 micrograms/ml) but that induced by thrombin (4 units/ml) was prevented. Nitroglycerin (10(-5) M) and the active metabolite of molsidomine, 3 morpholinosydnonimine (10(-5) M), did not modify the basal production of endothelin from the intima of intact porcine aortas. However, the nitrates fully inhibited the release of the peptide induced by thrombin (4 units/ml). The inhibitory effects of both 3-morpholinosydnonimine and nitroglycerin on the thrombin-stimulated release of endothelin were abolished in the presence of an inhibitor of soluble guanylate cyclase, methylene blue (10(-5) M). Thus, the thrombin-stimulated release of endothelin is inhibited by inactivation of thrombin with hirudin or by agents that mimic the effect of endothelium-derived nitric oxide. In contrast, the spontaneous production of endothelin is not modulated by the drugs. PMID- 1903678 TI - Time-cycled inverse ratio ventilation does not improve gas exchange during anaesthesia. AB - Inverse ratio ventilation (IRV) has been reported to improve oxygenation at lower peak airway pressures in patients with respiratory failure. Therefore we hypothesised that IRV might also improve oxygen exchange during anaesthesia. Conventional ratio ventilation (CRV) and IRV were compared in 24 low-risk surgical patients who were paralysed and whose lungs were ventilated with air/O2 by a non-rebreathing circuit and a Siemens 900-C servo ventilator. Two levels of time-cycled IRV (I:E ratios of 60/40 and 77/23) were bracketed by control periods with CRV (I:E ratio of 35/65). Inspired O2 fraction, O2 uptake and CO2 elimination, arterial blood gases, pulmonary ventilation and mechanics, heart rate and blood pressure were measured. From these data alveolar and dead space ventilation and four oxygen tension-based indices of gas exchange were calculated. During IRV, mean airway pressure (mean AWP) was increased but there were no changes in oxygen exchange indices, pulmonary mechanics, HR or BP. A sub set of the sample with moderately impaired oxygen exchange, defined as the upper quartile for (A-a)DO2, was examined separately with identical results. Multivariate models were tested to identify variables which predicted O2 exchange during CRV. Patient age was the only predictor consistently significant in all models. We conclude that age is an important determinant of impaired pulmonary oxygen exchange during anaesthesia, and that increasing mean AWP by TC-IRV has no beneficial effects on pulmonary mechanics or gas exchange. PMID- 1903681 TI - The impact of ovarian laser surgery on the gonadotrophin secretion in women with polycystic ovarian disease. AB - To evaluate the effects of ovarian surgery on the deranged episodic gonadotrophin release of women with the polycystic ovarian disease (PCOD), we studied 11 patients with the clinical and endocrinological features of PCOD before and after laparoscopic laser coagulations of ovarian surfaces and cysts. During both occasions, blood was collected at 15-min intervals for 8 h to determine LH and FSH secretory profiles and additionally for 3 h during GnRH injections (25 micrograms twice within 2 h) to assess pituitary responsiveness. Serum testosterone, androstendione and oestrogen (oestrone, oestradiol) levels were markedly reduced (P less than 0.05 or less) after surgery. Mean LH concentrations declined (P less than 0.001), while FSH levels increased (P less than 0.01) following laser treatments. The LH pulse frequencies (by Cluster analysis) did not change after ovarian surgery, but the LH pulse amplitudes were markedly reduced (P less than 0.01). Lower (P less than 0.05 or less) LH concentrations were attained in response to GnRH challenges, and the stimulated FSH release also tended to decrease after laser treatments. Thus, ovarian surgery in PCOD women resulted in reduced serum sex steroid concentrations and in divergent effects on serum LH and FSH levels. The attenuated pituitary LH responsiveness after ovarian surgery suggests action of sex steroids primarily at the pituitary site, while the increase in FSH concentrations may be attributed to other factors selectively modulating FSH release. PMID- 1903682 TI - Hepatobiliary dysfunction associated with total parenteral nutrition. AB - We have reviewed and discussed data concerning the development of hepatobiliary dysfunction in the patient requiring TPN. The data above can be summarised in a short statement--TPN-related hepatobiliary dysfunction is multifactorial. Despite all the factors discussed, the patients underlying disease state and the severity of the illness may be the most significant factor in the development of hepatobiliary dysfunction. With our current state of knowledge it is only possible for the clinician to be aware which of his patients are most likely to develop problems, and to forecast the type of dysfunction that is most likely to occur. There is no treatment--apart from stopping TPN--but there are certain methods by which the incidence and degree of dysfunction may be minimised, or some of the complications (e.g. gallstones) treated. Fortunately in most cases the degree of dysfunction is both self-limiting and reversible on cessation of TPN. PMID- 1903684 TI - Enteroliths of small bowel diverticula. AB - The formation of an enterolith within a diverticulum of the small bowel is a very rare occurrence. Complications of this include abscess formation, perforation and obstruction of the small bowel. We report four cases. One patient presented with intermittent pain relieved after calculus removal. One case was an incidental finding on barium follow through but presented with obstruction of the small bowel 3 years later. One patient presented with obstruction and perforation and a fourth patient showed several asymptomatic linear calculi in a single diverticulum. PMID- 1903683 TI - An updated comparison of drug dosing methods. Part II: Theophylline. AB - This article updates the previous review in the Journal regarding theophylline dosing methods. Among the predictive algorithms evaluated, the dose-titration scheme of Weinberger and Hendeles was extensively tested in 1073 asthmatic patients. When the scheme was followed appropriately, 78% of initial serum concentrations and 66% of repeat serum concentrations were within the therapeutic range of 10 to 20 mg/L. Several authors have also demonstrated that the 'condition correction factor' method for estimating theophylline clearance is of limited value. The individualised methods of Chiou, Koup and Vozeh have been evaluated in over 300 patients. In addition, numerous authors have reported the relative predictive performance of Bayesian dosing programs for theophylline. All methods continue to be a rapid and accurate means of individualizing dosing requirements for patients with a diverse range of theophylline disposition characteristics. Overall, the Bayesian predictions have been less biased and slightly more precise than the pharmacokinetics-based dosing methods. The most recent cost-effectiveness data has shown that a pharmacokinetic dosing program resulted in fewer toxic serum concentrations (18.9% vs 37.8%), a shorter mean duration of hospital stay (6.3 vs 8.7 days) and more therapeutic concentrations with subsequent oral therapy (71.1% vs 44.4%) than among control patients receiving dosages prescribed by physicians. PMID- 1903685 TI - Finite dose percutaneous drug absorption: a BASIC program for the solution of the diffusion equation. AB - A BASIC program to obtain the solution for the diffusion equation describing the finite dose percutaneous absorption pharmacokinetics is shown. Drug amount in the solution matrix, Av, that in the skin which is regarded as a simple diffusion membrane. As, and the drug flux from the skin which is provided by the local circulation per unit area, J, and the blood drug concentration. C, expressed as functions of time are obtained using Fourier series. Usually, a small number (less than 10) of series is enough to obtain the accurate values for Av, As, J, and C. It is also shown that the solution of the diffusion equation reported previously for the specific case where both the diffusion coefficient of a drug through the vehicle and skin-capillary clearance are very large is expressed as a limit. PMID- 1903686 TI - Antifertility effect of chronically administered Malviscus conzattii flower extract on fertility of male rats. AB - Quantitative evaluation of different varieties of germ cells at stage VII of the cycle, namely type A spermatogonia, pre-leptotene spermatocytes, mid-pachytene spermatocytes, step 7 and step 19 spermatids, along with radio-immunoassay of serum gonadotrophins (LH and FSH), testosterone and testicular testosterone were performed in rats of Wistar strain following treatment with methanolic extract of flowers of Malvaviscus conzattii (MVC) at a dose level of 800 mg/kg b.w. for 30 consecutive days. The treatment period just exceeds two cycles of the seminiferous epithelium of the Wistar strain rats (one cycle is 13.2 days). Reduction of step 7 and 19 spermatids at stage VII were observed. Significant reduction in serum concentration of LH and testosterone were observed three and four weeks after treatment. Testicular testosterone was also reduced. No distinct change in serum FSH concentration was recorded. The results indicate that the extract may have an inhibitory influence on gonadotrophin release which may be held responsible for the decline in testosterone production, leading to change in spermatogenesis caused by the MVC extract. Replacement with hCG along with MVC prevented degeneration of step 7 and step 19 spermatids, and enhanced testosterone production support the same idea. PMID- 1903687 TI - Shortcomings of using two jet nebulizers in tandem with an aerosol face mask for optimal oxygen therapy. AB - Herein, a laboratory model which allows measurement of simulated distal airway oxygen percentage at different breathing patterns is described to illustrate the shortcomings of conventional O2 devices and, in particular, the aerosol face mask with two jet nebulizers (AFM-DF) in tandem. A table showing the degree of dilution which occurred during simulation of various breathing patterns while using the AFM-DF is also presented. Data revealed that when 60 percent was desired, 13 of 27 measurements were less than 55 percent. The worst-case scenario for 60 percent desired was 48 percent measured. When 80 percent was desired, less than 70 percent was delivered in 24 of the 27 breathing patterns simulated. Less than 60 percent was measured on 12 occasions, with 51 percent being the lowest measurement. When 100 percent O2 was desired, less than 80 percent was measured in 25 of 27 breathing patterns. Less than 60 percent was measured in ten of those. Fifty percent was the lowest analyzed value for the 100 percent setting. The inadequacy of AFM-DF is described in three case studies. A high-flow nonrebreathing face mask (HFM) to address the subset of patients is also discussed. A peak inspiratory flow prediction chart is also documented and may be useful in setting optimal flows when using high-flow systems. The patients in whom intubation and mechanical ventilation (or use of continuous mask CPAP) are indicated can be more clearly identified with a trial of high-flow O2 therapy (with a system that assures adequate flow to meet the patient's peak inspiratory flow demands). In the remainder of patients, those higher-risk modalities will be precluded. PMID- 1903688 TI - The challenge of partnership: a national foster care charter in the United Kingdom. AB - The National Foster Care Association, in the United Kingdom, offers here its Foster Care Charter and its philosophy, which includes distinguishing "foster carers' from "foster parents' according to the plan for short- or long-term care. PMID- 1903689 TI - [Study of weight/height correlation to identify mild protein-energy malnutrition children 9 years old]. AB - This study was performed during April through July, 1987 in Beijing. Classified by international reference of weight for height, a sample of 292 children, 9-yrs of age from five primary schools in BJ. The main conclusions were: compared with control groups, the value of PWC 170 of MPEM groups was significantly lower, so were the anthropometric indicators. The values of mid-arm circumference showed no significant difference between the sexual groups, but there was very significant difference between the MPEM and control groups. The value of PWC170 of boys was significantly higher than that of girls. Hemoglobin mean values were within the normal range and no significant differences were found in all groups. This meant that the differences of PWC170 of groups were not due to anemia. Transferrin mean value was significantly lower in MPEM than in control groups in girls. The heart rates, during testing, were significantly higher in MPEM than in control groups. This difference was taken to be evidence that work performance was poorer in MPEM than in controls. PMID- 1903690 TI - [A review of the studies on fungi and mycotoxins in foodstuffs in Beijing during 1976-1986]. AB - Fungi and mycotoxins contaminating foods in Beijing during 1976-1986 were studied. A total of more than 5,000 food samples classified into 104 kinds of 16 types were examined of analysed. The results showed that the natural occurrence of Aflatoxin B1 in foods in Beijing was not serious, but from the results of analysis 59 cases of food poisoning and food seriously contaminated with moulds, the hazards of fungal contamination of food should receive serious consideration. In order to improve food hygiene and facilitate supervision the author suggested that a mycological standard should be established for marketing foods in China, such as grain, and beverage which are highly susceptible to fungal contamination. PMID- 1903691 TI - Mimosine reversibly arrests cell cycle progression at the G1-S phase border. AB - It has previously been demonstrated that the compound mimosine inhibits cell cycle traverse in late G1 phase prior to the onset of DNA synthesis (Hoffman BD, Hanauske-Abel HM, Flint A, Lalande M: Cytometry 12:26-32, 1991; Lalande M: Exp Cell Res 186:332-339, 1990). These results were obtained by using flow cytometric analysis of DNA content to compare the effects of mimosine on cell cycle traverse with those of aphidicolin, an inhibitor of DNA polymerase alpha activity. We have now measured the incorporation of bromodeoxyuridine into lymphoblastoid cells by flow cytometry to determine precisely where the two inhibitors act relative to the initiation of DNA synthesis. It is demonstrated here that mimosine arrests cell cycle progression at the G1-S phase border. The onset of DNA replication occurs within 15 min of releasing the cells from the mimosine block. In contrast, treatment with aphidicolin results in the accumulation of cells in early S phase. These results indicate that mimosine is a suitable compound for affecting the synchronous release of cells from G1 into S phase and for analyzing the biochemical events associated with this cell cycle phase transition. PMID- 1903692 TI - The force of change in the management of squamous-cell cancer of the anal canal. PMID- 1903693 TI - [Therapy of multiple myeloma by allogeneic bone marrow transplantation]. AB - Multiple myeloma of IgG kappa type was diagnosed in a 42-year-old man with bone pains, dyspnoea on exertion and increasing drowsiness. Six chemotherapy cycles extending over 14 weeks and consisting of 15 mg/m2 melphalan intravenously on day 1 and 60 mg/m2 prednisolone orally on days 1-4 produced a partial remission. As the HLA-identical sister of the patient was willing to donate bone marrow, an allogeneic marrow transplantation was planned. After 7 days' conditioning treatment (hyperfractionated whole-body irradiation with 12 Gy, chemotherapy with 70 mg/m2 melphalan and 60 mg/kg cyclophosphamide), 4.2 x 10(8) nucleated cells of donor marrow were infused per kg recipient body-weight through a central venous catheter. Despite prophylaxis with short-course methotrexate and cyclosporin, an acute graft-versus-host reaction of grade II-III occurred on day 26, though it settled almost completely after treatment with daily 2 mg/kg prednisone and monoclonal interleukin-2 receptor antibodies (B-B10, daily 10 mg). On day 100 after the marrow transplantation, marrow puncture showed the picture of complete remission with normal regeneration of haemopoietic cells. Allogeneic marrow transplantation may therefore be considered as a new and promising mode of treatment for younger patients with multiple myelomas. PMID- 1903694 TI - Effect of the cardiac inotropic drug, OPC 8212, on pituitary-thyroid function in the rat. AB - 3,4-Dihydro-6-[4-(3,4-dimethoxybenzoyl)-1 piperaznyl]-2(1H)-quinolinone (OPC 8212) is a new synthetic quinolinone with potent cardiac inotropic action in man. Long term oral administration of OPC induces goiter and thyroid tumor formation in rats, associated with decreases in serum T4 and increases in serum TSH concentrations. Studies were carried out to explore the mechanisms responsible for these drug induced abnormalities. OPC 8212, administered for 1 week at doses of 500 and 2000 mg/kg.day mixed with the diet, resulted in an increase in thyroid weight, a decrease in circulating T4 and free T4 concentrations and an increase in serum TSH concentrations. OPC decreased the 5'-deiodinase (5'-D) activity in liver homogenates and increased the 5'-D activity in pituitary homogenates, consistent with hypothyroidism. OPC 8212 did not affect thyroid iodine metabolism and hormone synthesis or the binding of T4 to serum binding proteins. The hepatic uptake of 125 I-T4 4 h after T4 administration was significantly increased in OPC 8212 treated rats. The biliary excretion of administered 125 I-T4 was increased in OPC 8212-treated rats and most of the increase was due to an increase in the excretion of T4-glucuronide. Hepatic T4-glucuronyltransferase activity measured in vitro in OPC 8212 treated rats was increased as compared to that of controls. It is concluded that the effect of OPC 8212 on lowering serum T4 with a compensatory rise in TSH leading to goiter formation is due to a drug-induced increase in hepatic T4 disposal. The induction of T4-glucuronyl-transferase appears to play an important role in the increased biliary excretion of T4 in OPC 8212-treated rats. PMID- 1903695 TI - Control of intracellular calcium redistribution by guanine nucleotides and inositol 1,4,5-trisphosphate in permeabilized GH4C1 cells. AB - In GH4C1 rat pituitary cells, a GTP-binding protein appears to be involved in signal transduction between the TRH receptor and phospholipase C. In certain other cell types, another role for GTP has been reported, namely regulation of Ca2+ translocation from one intracellular pool to another. Using digitonin permeabilized GH4C1 cells, we have investigated whether an analogous process occurs in pituitary cells. In permeabilized GH4C1 cells, TRH, inositol 1,4,5 trisphosphate (IP3), and nonhydrolyzable GTP analogs guanosine 5'-O-(3 thiotriphosphate) (GTP gamma S) and 5'-guanylyl imidodiphosphate each increased free Ca2+ concentration [( Ca2+]). Unlike several other systems, GTP did not increase [Ca2+]. Guanosine 5'-O-(2-thiodiphosphate) inhibited Ca2+ release induced by both TRH and GTP gamma S. Heparin abolished IP3-induced Ca2+ release but did not prevent Ca2+ release induced by TRH or GTP gamma S, suggesting a mechanism for their actions that did not depend solely on IP3 production. Neomycin inhibited GTP gamma S-induced Ca2+ release, but it did not prevent TRH- or IP3-induced Ca2+ release. In the absence of ATP, GTP gamma S did not elevate [Ca2+], although TRH and IP3 did, suggesting that ATP-dependent sequestration of Ca2+ was necessary for the action of GTP gamma S in this system, but not for TRH and IP3. Repeated additions of IP3 resulted in an attenuation of the response to IP3- GTP gamma S, which itself increased [Ca2+] after IP3 attenuation, restored the attenuated Ca2+ response to IP3. We conclude that, in permeabilized GH4C1 cells, GTP gamma S as well as TRH cause intracellular Ca2+ release; however, their mechanisms of action are, at least in part, distinct. Furthermore, the IP3 depletable Ca2+ pool can be refilled from a GTP gamma S-sensitive compartment via Ca2+ transport through the cytosol. PMID- 1903696 TI - Tumor necrosis factor-alpha increases release of arachidonate and prolactin from rat anterior pituitary cells. AB - We investigated the effect of tumor necrosis factor-alpha (TNF alpha), a product of activated macrophages, on the release of arachidonate from dispersed anterior pituitary cells. Primary cultures of anterior pituitary cells from rats were preincubated with [3H]arachidonate to label their phospholipid-containing components. The cells were then washed and incubated with vehicle or test agents, and PRL release into the medium and [3H]arachidonate cleaved from phospholipid were measured. TNF alpha significantly increased the release of both PRL and [3H] arachidonate release in a time- and dose-dependent manner. Other cytokines, such as interleukin-1 alpha, interleukin-1 beta, and gamma-interferon, had no effect on [3H]arachidonate release. To define the role of calcium in TNF alpha-induced arachidonate release, dispersed pituitary cells were incubated with low calcium medium, which decreased arachidonate release in response to TNF alpha. TNF alpha potentiated the release of [3H]arachidonate and PRL promoted by phospholipase-A2 and melittin, and markedly shifted the dose-response curve to the left. Inhibitors of phospholipase-A2, such as p-bromophenacyl bromide and quinacrine, had no effect on TNF alpha-induced [3H]arachidonate and PRL release. BW755C, an inhibitor of the conversion of arachidonate to its metabolites, decreased TNF alpha-induced PRL release, while indomethacin, a prostaglandin synthesis inhibitor, had no effect on TNF alpha-induced PRL release. These data indicate that arachidonate metabolites may be involved in the process of TNF alpha-induced PRL release. PMID- 1903698 TI - Differential responsiveness of the pituitary-thyroid axis to thyrotropin releasing hormone in mouse lines selected to differ in central nervous system sensitivity to ethanol. AB - Long-sleep (LS) and short-sleep (SS) mice are genetic lines that differ in central nervous system sensitivity to ethanol. The possible role of TRH in mediating the difference in the thyroid status between these two lines was investigated. An increase in TRH gene expression in the paraventricular nucleus and TRH peptide levels in the hypothalamus between postnatal days 8-14 in both SS and LS mice coincided with increased circulating levels of thyroxine during this critical period of central nervous system development. No significant differences in TRH biosynthesis were observed between LS and SS mice during this time. Exogenous administration of TRH to LS and SS mice on day 8, when endogenous serum thyroxine levels were equivalent, resulted in a greater increase in serum thyroxine in SS mice (150%) than LS mice (51%). The differential response to the TRH stimulation test was also present on day 14 (SS, 43%; LS, 18%). The differential responsiveness of the pituitary-thyroid axis to exogenous TRH paralleled the differential increase in endogenous serum thyroxine observed between day 8 and 14 in these mice. Administration of TRH to day 20 and adult (60 days) LS and SS mice resulted in nearly equivalent (approximately 75%) increases in free thyroxine serum levels, yet the magnitude of thyroxine release was 50% greater in SS mice, due perhaps to between-line differences within the thyroid glands. It is unlikely that dissimilar endogenous levels of TRH account for the intrinsic difference in the thyroid status in LS and SS mice. Instead, the increased pituitary-thyroid responsiveness to TRH in SS mice during the second postnatal week may translate into increased functional capacity of the thyroid gland in adult SS relative to LS mice. PMID- 1903697 TI - Protein kinase C activation mimics but does not mediate thyrotropin-induced desensitization of adenylyl cyclase in cultured dog thyroid cells. AB - The mechanism and site(s) of the defect responsible for desensitization to hormone stimulation of adenylyl cyclase (AC) vary with cell type. Plasma membrane preparations were assayed after treatment of primary cultured dog thyroid cells to determine the role of the TSH receptor, stimulatory and inhibitory guanine nucleotide binding proteins (Gs and Gi), and catalytic unit in AC desensitization. Exposure of cells to TSH or the phorbol ester, 12-O tetradecanoyl-phorbol-13-acetate (TPA), caused time dependent decreases in TSH stimulated AC and [125I]TSH binding with approximately 50% decreases seen after 18 h; Bt2cAMP was unable to reproduce the TSH effect. Whereas TSH treatment caused concomitant decreases (approximately 25%) in both cyclase activity and [125I]TSH binding after 2 h, TPA treatment decreased AC activity after 6 h and binding only after 18 h. The protein kinase C inhibitor, H-7, prevented TPA induced but not TSH-induced effects on AC and hormone binding. Membrane AC activation by cholera toxin or forskolin was not altered by 18 h pretreatment of cells with TSH or TPA, indicating that these agents had no apparent effect on intrinsic functionality of either Gs or the catalytic unit. TSH or TPA pretreatment of cells reduced subsequent toxin-mediated AD[32P]-ribosylation of Gs and Gi in isolated membranes. However, the TSH- and TPA-induced decreases in AD[32P]-ribosylation and desensitization do not appear to be due to endogenous ribosylation of G proteins, since treatment of cells with pertussis toxin, for example, to endogenously ribosylate Gi, both increased TSH-stimulated AC activity and failed to affect the ability of TSH or TPA to desensitize. Thus, in this system, although specific hormone-induced AC desensitization and receptor down regulation conform to several aspects of classic homologous processes, similar effects are also induced by a nonreceptor (phorbol ester) pathway; desensitization, however, can precede down-regulation, possibly due to receptor Gs uncoupling. PMID- 1903699 TI - Proteolytic processing of thyroglobulin by extracts of thyroid lysosomes. AB - The release of T4 and T3 from the prohormone thyroglobulin (Tg) occurs in thyroid lysosomes. To examine the role of cathepsin-B, -D, and -L, the three major endopeptidases in this process, we incubated rabbit [125I]Tg, labeled in vivo, with lysosomal extracts from human thyroids. Iodopeptide formation was evaluated by polyacrylamide gel electrophoresis in sodium dodecyl sulfate after short term incubations (20-45 min), while iodoamino acid release was assessed by paper chromatography after long term incubations (8 and 24 h). Using pepstatin to inhibit cathepsin D, Z-Phe-Ala-CHN2 to inhibit both cathepsin B and L, and Z-Phe Phe-CHN2 to selectively inhibit cathepsin L, we obtained the following results: 1) blocking of all three endopeptidases reduced both iodopeptide formation in short term experiments and iodoamino acid release in long term experiments by 80 90%; 2) iodopeptide formation was reduced by 85% with Z-Phe-Ala-CHN2, by 56% with Z-Phe-Phe-CHN2, and by 26% with pepstatin; 3) iodoamino acid release was reduced by 60-80% with Z-Phe-Ala-CHN2 and by 40-50% with either Z-Phe-Phe-CHN2 or pepstatin at 8 h, but by less than 20% at 24 h; pepstatin and Z-Phe-Phe-CHN2 together reduced iodoamino acid release by 80% and 60% at 8 and 24 h, respectively. Limited hydrolysis of Tg by lysosomal enzymes produced at least eight peptide fragments of less than 100,000 mol wt. Three of these, together representing 32% of the 125I released, resulted from cleavages in the C-terminal region of Tg corresponding to residues 2487, 2393, and 2390 of cDNA-derived human Tg. Several other peptides, together containing 38% of the 125I released, included the N-terminus of Tg. These C-terminal and N-terminal fragments contained three of Tg's four major hormonogenic sites, but none of the cleavage sites fell close to the hormone sites themselves. We conclude that 1) the formation of discrete iodopeptides precedes the release of iodothyronines and iodotyrosines from Tg; 2) the cysteine proteinases are more important than cathepsin D in this process; and 3) these endopeptidases selectively cleave Tg to favor the production of hormone-containing intermediates for subsequent processing by exopeptidases. PMID- 1903700 TI - Aluminum-induced mitogenesis in MC3T3-E1 osteoblasts: potential mechanism underlying neoosteogenesis. AB - We recently reported that aluminum administration to beagles stimulates uncoupled bone formation in the marrow cavity which increases trabecular bone volume and generates new osseous networks within the axial skeleton. To investigate whether this osteogenic process results from direct stimulation of bone cell replication, we examined the mitogenic effects of aluminum on undifferentiated osteoblasts derived from the MC3T3-E1 clonal cell line. Addition of AlCl3 (1-50 microM) to serum-free culture medium of quiescent osteoblasts resulted in a dose-dependent increase in [3H]thymidine incorporation into DNA and a concordant increase in cell number to 48% of the density achieved at the maximum replicative rate induced by fetal bovine serum (FBS). The time course of aluminum-induced mitogenesis was similar to that of FBS, with onset of DNA synthesis detectable by 12 h and progressive increases in replicative rates observed over a 48-h study period. Moreover, maximal stimulation of DNA synthesis by AlCl3 and that by FBS were not additive, whereas aluminum exerted additional effects on cell replication when combined with low FBS concentrations. Analysis of cell cycle kinetics indicated that aluminum, analogous to FBS, influences the osteoblast replicative activity by inducing transition from the G0 to the S phase of the cell cycle. In addition, exposure of cells to aluminum resulted in rapid accumulation of c-fos mRNA by 30 min, indicating that aluminum, like fetal bovine serum, induced expression of growth-regulating genes. Deferoxamine mesylate, a chelator of aluminum, blocked the replicative actions of aluminum in a dose dependent fashion. In contrast, pertussis toxin, a specific inhibitor of certain G-proteins, had no effect on the mitogenic effects of aluminum, indicating that aluminum-induced mitogenesis occurs by a pertussis toxin-insensitive pathway. Though the particular cellular pathway remains to be defined, these data provide initial evidence that aluminum-induced neoosteogenesis may depend upon direct stimulation of osteoblast replication. PMID- 1903701 TI - Synergistic effects of follicle-stimulating hormone and testosterone on the maintenance of spermiogenesis in hypophysectomized rats: relationship with the androgen-binding protein status. AB - The present study examined the relationship between the functional status of Sertoli cells and the maintenance and restoration of spermatogenesis in immature hypophysectomized (HPX) rats given various doses of exogenous testosterone with or without daily injections of FSH for 90 days. Subcutaneous implantation of a 2- to 10-cm testosterone capsule (TC) increased serum testosterone levels of HPX rats 2-10 times above the normal control levels, but did not significantly increase the testicular testosterone level. Daily injections of FSH significantly increased the accumulation of testosterone in testes of TC-implanted HPX rats. Maintenance of early spermiogenesis was observed in all TC-implanted animals. Although elongated spermatids were present, step 18-19 spermatids at the luminal edge of stages VII-VIII epithelium were only observed in rats bearing 10-cm TC implants. Daily injection of FSH resulted in the completion of spermiogenesis in all TC-implanted animals, and the number of step 18-19 spermatids was dependent on the length of TC implants used. These results demonstrate the importance of the synergism of FSH and testosterone in the final steps of spermiogenesis. The androgen-binding protein (ABP) content per testis of the HPX rats was stimulated by TC implants. However, a significant increase in epididymal ABP was only noted in rats bearing 10-cm TC implants. Injection of FSH resulted in a significant increase in the testicular ABP content in rats bearing 2- or 5-cm TC, but not in those with 10-cm TC implants. In addition, the epididymal ABP content was significantly stimulated by FSH in all TC-implanted animals. The ABP status in the testis and its transport toward the epididymis are closely related to the extent of maintenance of spermiogenesis. It is speculated that the production of ABP by Sertoli cells and the biochemical properties of ABP molecules may have some role in the control of the final steps of spermiogenesis. PMID- 1903702 TI - Differential regulation of carbonic anhydrase II by androgen and estrogen in dorsal and lateral prostate of the rat. AB - Hormone regulation of carbonic anhydrase II (CA II) was studied in rat dorsal and lateral prostate. CA II is a major soluble protein in these accessory sex glands. The immunoelectronmicroscopy showed that CA II is expressed in their epithelial cells only. For studies on hormone regulation, adult male rats were castrated for 2 or 7 days. Groups of 7-day castrates and normal rats were treated daily either with testosterone or 17-beta-estradiol for 6 days and 2-day castrates for 1 day. CA II protein was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and quantified by RIA. The levels of CA II mRNA were studied by Northern blotting and hybridization of total RNA with a 32P-labeled mouse CA II cDNA clone. Castration of the rats decreased the concentration of CA II in lateral prostate but increased in dorsal prostate. These changes were reversed in both prostatic lobes by testosterone treatment. Estrogen treatment of castrated rats enhanced CA II concentration in lateral prostate but no effects were seen in the dorsal prostate of the same animals. In normal rats estrogen increased CA II concentration of dorsal prostate but there was no change in lateral prostate. Corresponding changes were observed in the levels of CA II mRNA in both tissues. The morphometric analyses showed that the castration- and hormone-induced changes of the mRNA and protein levels of the exclusively epithelial CA II could not be explained by any alterations in the proportions of epithelial and stromal components of the glands after hormone manipulations. The results demonstrate the differential steroid regulation of CAII in two prostatic lobes. Androgen regulates the expression of CAII at messenger RNA level, but the responses of CAII to testosterone are opposite in dorsal and lateral prostate. Estrogen increases CA II expression in lateral prostate but in dorsal prostate the castration-like effects of estrogen on CAII expression are probably indirect. PMID- 1903703 TI - Multiple enchondromatosis (Ollier's disease) complicated by malignant astrocytoma. PMID- 1903704 TI - Intraarterial digital subtraction angiography in bronchogenic carcinoma treated with bronchial artery infusion. AB - Intraarterial digital subtraction angiography (IADSA) has been used with advantage for control of the results of bronchial artery infusion of drugs for primarily unresectable bronchogenic carcinoma. The IADSA has been performed as road mapping prior to therapy. Drug treatment has been performed with four different regimes, depending on tumour type. Debulking and in some cases complete healing are the results, which are superior to other reported treatments. PMID- 1903705 TI - Molecular cloning of rat interleukin 4 cDNA and analysis of the cytokine repertoire of subsets of CD4+ T cells. AB - Rat peripheral CD4+ T cells may be subdivided into two functionally distinct subpopulations (OX-22highCD4+ and OX-22lowCD4+) on the basis of their reactivity with the monoclonal antibody MRCOX-22, which recognizes a restricted epitope on the leukocyte common antigen (LCA, CD45). Previous studies have demonstrated the increased activity of the OX-22highCD4+ subset in assays of cell-mediated reactivity, whereas the reciprocal OX-22lowCD4+ subset provides the majority of help for B cells in secondary antibody responses. Analyses of in vivo function have subsequently shown that the autoreactive activity associated with the OX 22highCD4+ subset can be inhibited through a suppressor activity within the OX 22lowCD4+ subset, indicating a further immunoregulatory role for these cells. Since the differential production of lymphokines such as interferon-gamma (IFN gamma) and interleukin 4 (IL4) is believed to regulate alternative effector responses to a particular antigen, we have compared the lymphokine mRNA profiles of activated OX-22highCD4+ and OX-22lowCD4+ subsets using nucleic acid probes specific for rat IL 2, IFN-gamma and IL4, the latter of which has been isolated by a polymerase chain reaction cloning technique and its sequence is described. A higher frequency of cells expressed IL 2 mRNA in the OX-22high subset, in accordance with the relative levels of IL2 protein produced. In contrast, more IFN-gamma mRNA was detected in the OX-22lowCD4+ subset 24 h after mitogenic stimulation although these cells have consistently been shown to produce less IFN gamma protein than the OX-22highCD4+ subset. This apparent paradox was resolved by the finding that the IFN-gamma mRNA levels in the OX-22lowCD4+ subset declined rapidly after 24 h while the levels continued to rise in the OX-22highCD4+ population such that at 48 h the relative levels were reversed. We have also demonstrated a higher level of IL4 mRNA expression within the OX-22lowCD4+ subset, which is undoubtedly involved in the increased B cell helper activity mediated by this subpopulation and may be responsible, in part, for their active suppression of cell-mediated immune responses. PMID- 1903706 TI - Molecular analysis of V kappa III variable regions of polyclonal rheumatoid factors during rheumatoid arthritis. AB - We report the first molecular characterization of V kappa regions of the main human autoantibodies occurring during rheumatoid arthritis, the polyclonal rheumatoid factors. Using two sets of polymerase chain reactions in order to amplify the cDNA derived from both peripheral blood and synovial fluid rheumatoid factor-secreting cells, nucleotide analysis of the V kappa III family usage shows the following: (a) at least three different V kappa III genes are used to encode polyclonal rheumatoid factors in a single patient, (b) each one of these genes seems more or less somatically mutated (from 1 to 14 mutations), (c) the mutation process preferentially affects the complementarity determining regions suggesting a selective pressure of antigen and (d) there is no clear difference between the mutation rates affecting the synovial fluid and peripheral blood rheumatoid factor-secreting cells. These results are able to explain some of the known idiotypic differences between monoclonal and polyclonal rheumatoid factors in humans. They also provide evidence that polyclonal autoantibodies arising during an autoimmune disease can be the products of multiple somatically mutated genes and suggest that this process is antigen driven, whether this antigen is the Fc piece of IgG or another unknown antigen. PMID- 1903707 TI - Diversity in antigen recognition by Mycobacterium tuberculosis-reactive T cell clones from the synovial fluid of rheumatoid arthritis patients. AB - In a previous study we have shown that synovial fluid mononuclear cells from many rheumatoid arthritis (RA) patients exhibit an enhanced response to M. tuberculosis antigens as compared to peripheral blood mononuclear cells. The 65 kDa heat-shock protein of M. tuberculosis was shown not to play an important role in this response, therefore other mycobacterial proteins must be involved. In this study we have investigated the possibility that synovial fluid T cells from RA patients predominantly recognize a limited number of M. tuberculosis antigens, as a result of a lesion-specific activation of only those M. tuberculosis reactive T cells that have cross-reacted with joint-related autoantigens. From the synovial fluid of four RA patients M. tuberculosis-reactive T cell clones were isolated and analyzed for their phenotype, HLA-DR restriction and proliferation to immunoblot fractions containing sodium dodecyl sulfate polyacrylamide gel-separated M. tuberculosis proteins of known molecular weight range. The overall M. tuberculosis immunoblot recognition pattern of the clones was strikingly heterogeneous. Within a panel of 15 clones 12 different antigenic specificities could be distinguished. In other words, we did not observe a dominant recognition of a few M. tuberculosis antigens by synovial fluid T cells. This argues against the hypothesis that the elevated synovial T cell reactivity against M. tuberculosis is a reflection of an in vivo expansion of a limited number of different types of M. tuberculosis-reactive T cells as a result of a cross-reaction with putative joint autoantigens. PMID- 1903708 TI - VH gene usage in humans: biased usage of the VH6 gene in immature B lymphoid cells. AB - Preferential usage of JH-proximal VH genes has been demonstrated in immature murine B cell repertoires. To determine whether this phenomenon is also evident in human repertoires, we studied utilization of VH6, the most JH-proximal human VH gene. Examination of VH gene usage in a panel of precursor B cell acute lymphoblastic leukemia samples indicated that 15% of the IgH rearrangements utilized VH6. VH6 is a single-member family in a total repertoire of 100-200 VH genes; thus, if usage were purely random, one would expect VH6 rearrangement frequency to be less than 1%. Analysis of VH gene usage in normal lymphoid tissues also revealed biased usage of VH6. VH6 was preferentially utilized in 16- to 24-week-old fetal liver as compared to adult peripheral blood mononuclear cells or spleen. Possible implications of the conservation of preferential usage of JH-proximal genes in both immature murine and human repertoires are discussed. PMID- 1903709 TI - Human antibody production in transgenic mice: expression from 100 kb of the human IgH locus. AB - In order to study the requirements for a human antibody repertoire to be engineered in transgenic animals, we have created mouse strains that express human immunoglobulin genes from 100 kb of cosmid DNA. Undisrupted integration of the human DNA in the mouse germ line, encoding germ-line V,D,J and the Cmu constant region, was achieved, and proved sufficient for the production of human IgM in the mouse serum. Co-integration of one cosmid (containing the VH6 gene and a 36-kb region of the J-proximal D cluster) with a second cosmid (containing VH26, a further 38-kb of the D cluster, JH and Cmu) results in V-D-J rearrangements in the transgenic mice, similar to those seen in human DNA, were found only in spleen but not in thymus. Random hybridomas made from these transgenic mice show heterogeneous rearrangements of the human transgenes. Sequences of V-D-J units derived from transgene rearrangements reveal extensive N region and apparent D segment diversity. These results show that utilisation of human Ig genomic segments does occur in transgenic mice, paving the way for the derivation of a mouse strain that makes authentic human antibodies from inserted heavy and light chain gene loci. PMID- 1903711 TI - Effects of prenatal protein malnutrition on kindling-induced alterations in dentate granule cell excitability. II. Paired-pulse measures. AB - The effects of prenatal protein malnutrition on kindling-induced changes in inhibitory modulation of dentate granule cell activity were examined by analysis of extracellular field potentials recorded from the granule cell layer of the dentate gyrus in response to paired-pulse stimulation of the perforant pathway in freely-moving rats. Since we have shown that kindling results in enhanced synaptic transmission at the level of the perforant path/granule cell synapse (see preceding paper), we sought to determine if the kindling process might induce changes in inhibitory modulation of granule cell excitability which could be involved in the slower acquisition of the kindled state we have previously reported in malnourished animals. Beginning at 120-150 days of age, the response of dentate granule cells to paired-pulse stimulation of the perforant path was examined at interpulse intervals (IPIs) ranging from 20-1000 ms. A paired-pulse index (PPI) was constructed based on the mean percent change in population spike amplitudes of the two responses resulting from application of the pulse pair. PPI measures obtained during the kindling process were compared with individual prekindling measures to determine the mean percent change in excitatory/inhibitory modulation of granule cell activity. Significant inhibition of the second population response was apparent at all IPIs tested for both diet groups following the first kindled afterdischarge.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1903710 TI - Effect of norepinephrine depletion on audiogenic-like seizures elicited by microinfusion of an excitant amino acid into the inferior colliculus of normal rats. AB - Infusions of an excitant amino acid, N-methyl-D-aspartate (NMDA) into the inferior colliculus (IC) render normal rats susceptible to audiogenic seizures (AGS) and/or spontaneous audiogenic-like seizures without tonic components. The excess excitant amino acid in the IC and the anticonvulsant effects of NMDA antagonists in genetically epilepsy-prone rats (GEPRs), along with innate norepinephrine (NE) deficits and anticonvulsant effects of NE agonists in these animals suggest a mutual role of excitant amino acids and NE in regulating AGS in GEPRs. Saline or 6-hydroxydopamine (6-OHDA, 4 micrograms/side in 2 microliters) was infused bilaterally into the locus coeruleus (LC) of normal male rats and guide cannulas were implanted into the IC. Two weeks later, NMDA was infused bilaterally into the IC (0.5 microliters; 10 nmol/side) and 10 min later the rats were subjected to an electric bell (110 db, 60 s) unless preceded by spontaneous tonic seizures. Tonic seizures were not observed in male rats following NMDA infusions in rats with LC infusions of saline. However, a marked increase in the incidence of tonic seizures was observed in the 6-OHDA-treated rats which were markedly depleted of brain NE as determined by HPLC. These findings indicate that a NE deficit greatly enhances the incidence of tonic convulsions and support the hypothesis that an excitant amino acid excess in the GEPR IC may act to initiate AGS, whereas the NE deficit may allow expression of the tonic components of AGS seen in some GEPRs. PMID- 1903712 TI - The influence of "essential" phospholipids (EPL) on phase-I- and phase-II reactions and on the glutathione status in the liver of aging rats. AB - "Essential" phospholipids (EPL; polyene-phosphatidylcholine) were administered orally to aging male rats in doses of 100 and 300 mg/kg b.wt. over 10 weeks. One and 7 days after the last treatment cytochrome P-450 concentration, epoxide hydrolase and glutathione-S-transferases were found to be unchanged, but ethylmorphine N-demethylation, ethoxycoumarin O-deethylation and UDP glucuronosyltransferase activities were enhanced, as were the concentrations of both reduced and oxidized glutathione, the values being similar to those in young adult rats. These results are discussed in terms of an increase in endoplasmic reticulum membrane fluidity. PMID- 1903713 TI - Functional significance of sequences following the TATA box of an immunoglobulin promoter studied by random mutagenesis. AB - We have investigated the importance of sequences downstream to the TATA box of an immunoglobulin promoter by transfection and in vitro transcription assays. A sequence from -11 to +10 with respect to the transcriptional start site was synthesised by a procedure allowing for random misincorporation of nucleotides. The pool of mutant oligonucleotides was cloned into the respective position of a vector carrying a fusion of a synthetic immunoglobulin heavy chain promoter with the human growth hormone gene. From 200 clones sequenced, 115 were mutants with at least one nucleotide exchange in every position. Whereas most mutations are of minor functional importance, changes at or near the transcriptional start site reduce the promoter activity considerably. PMID- 1903714 TI - High affinity quinuclidinyl benzilate binding to rat parotid membranes requires muscarinic receptor. G protein interactions. AB - The binding of the non-selective muscarinic antagonist [3H]quinuclidinyl benzilate (QNB) to rat parotid membranes was characterized. Under equilibrium conditions, [3H]QNB bound to a homogenous population of muscarinic receptors (Kd, 118 +/- 19 pM; Bmax, 572 +/- 42 fmol/mg membrane protein, n = 12). The addition of G protein activators AlF4- or guanosine-5'-O-(3-thiotriphosphate) (GTP gamma S) + Mg2+ increased the Kd by 77 +/- 7% (n = 4, P less than 0.05) and 83 +/- 27% (n = 7, P less than 0.05), respectively, without a change in the Bmax or homogeneity of the binding site. GTP gamma S added without exogenous Mg2+ did not affect [3H]QNB binding. Thus, optimal QNB binding requires a muscarinic receptor/G protein interaction. PMID- 1903715 TI - Cyanobacterial thylakoid membrane proteins are reversibly phosphorylated under plastoquinone-reducing conditions in vitro. AB - Reversible, light-dependent protein phosphorylation was observed in isolated thylakoid membranes of the cyanobacterium Synechococcus 6301. A polypeptide of 15 kDa in particular was phosphorylated under plastoquinone-reducing conditions and was not phosphorylated under plastoquinone-oxidising conditions. Phosphorylation and dephosphorylation reactions involving this and several other membrane polypeptides showed sensitivity to inhibitors of protein kinases and phosphatases. Changes in phosphorylation state correlated with changes in low temperature fluorescence emission characteristic of changes in excitation energy distribution between the photosystems. The 15 kDa phosphopolypeptide is likely to be involved directly in light state adaptations in cyanobacteria. PMID- 1903716 TI - Carotenoid composition in the cyanobacterium Phormidium laminosum. Effect of nitrogen starvation. AB - When pigments of the non-N2-fixing cyanobacterium Phormidium laminosum were carefully extracted and analyzed in a completely O2-free atmosphere, by either high performance liquid chromatography (HPLC) or thin layer chromatography (TLC), the presence of only two carotenoids (namely, beta-carotene and nostoxanthin) was detected. However, exposure of pigments to an air atmosphere during their manipulation led to the rapid appearance in the organic extracts of at least three additional carotenoids (identified as caloxanthin, zeaxanthin and beta cryptoxanthin). This fact could explain the presence in cyanobacteria of such hydroxylated derivatives of beta-carotene widely reported in the literature. Nitrogen starvation also resulted in an important decrease on the relative beta carotene/nostoxanthin content of cells, suggesting that this nutritional condition affects thylakoid membranes more drastically than cytoplasmic membranes. PMID- 1903717 TI - Purification and characterization of human platelet phospholipase A2 which preferentially hydrolyzes an arachidonoyl residue. AB - A phospholipase A2 with an arachidonoyl residue preference was purified about 11,700-fold from human platelet soluble fraction to near homogeneity. The purified phospholipase A2 exhibited a molecular mass of about 90 kDa on SDS polyacrylamide gel electrophoresis and hydrolyzed phospholipids with an arachidonoyl residue more effectively than those with a linoleoyl residue. The catalytic activity of the purified enzyme detected with phosphatidylcholine as a substrate increased sharply between 3 x 10(-7) and 10(-6) M free calcium ion. Thus, the 90-kDa phospholipase A2 is considered to be a novel enzyme, distinct from the 14-kDa one previously purified from human platelets. The 90-kDa phospholipase A2 may participate mainly in arachidonate metabolism of platelets. PMID- 1903718 TI - In-vitro matured human macrophages express Alzheimer's beta A4-amyloid precursor protein indicating synthesis in microglial cells. AB - Microglia which are consistently associated with Alzheimer's disease (AD) senile plaques are part of the mononuclear phagocyte system. In-vitro matured human monocyte-derived macrophages feature many immunological characteristics of microglia. We found strong constitutive expression of Alzheimer's beta A4-amyloid precursor protein (APP) in human mononuclear phagocytes after terminal in-vitro maturation from monocytes to macrophages. Amyloid has previously been found to be associated with microglia in AD brains, however, it remained unclear whether the material was synthesized in or had been phagocytosed by the cells. The findings presented here support the assumption that brain microglia may contribute to APP synthesis in AD brain. PMID- 1903719 TI - G-proteins in etiolated Avena seedlings. Possible phytochrome regulation. AB - The molecular mechanism of light signal transduction in plants mediated by the photosensor phytochrome is not well understood. The possibility that phytochrome initiates the signal transduction chain by modulating a G-protein-like receptor is examined in the present work. Etiolated Avena seedlings contain G-proteins as examined in terms of the binding of GTP as well as by cross-reaction with mammalian G-protein antibodies. The binding of GTP was regulated in vivo by red/far-red light. The possible involvement of G-proteins in the phytochrome mediated signal transduction in etiolated Avena seedlings has been implicated from the study of the light regulated expression of the Cab and phy genes. PMID- 1903720 TI - Protein phosphorylation in isolated nuclei from etiolated Avena seedlings. Effects of red/far-red light and cholera toxin. AB - We have studied the phosphorylation/dephosphorylation of several nuclear proteins in isolated nuclei from etiolated Avena seedlings as a function of red/far-red light. The effect of stimulatory (ADP-ribosylation by cholera toxin) or inhibitory (GDP beta S) conditions for GTP-binding proteins was also studied. Red or far-red light enhanced the phosphorylation level of 2 nuclear proteins with molecular masses of 75 and 60 kDa. The phosphorylation pattern was affected by the addition of cholera toxin or GDP beta S to the isolated nuclei. At least 2 proteins with molecular masses of 24 and 75 kDa cross-reacted by Western blot with GTP-binding protein antibodies. PMID- 1903721 TI - Structural analysis by circular dichroism of some enzymes involved in plant cell wall degradation. AB - Three enzymes which degrade different polysaccharide components of plant cell walls have been characterized by circular dichroism (CD). A bacterial endoglucanase, which in the native state forms part of a multiprotein cellulase complex, showed a tendency to form aggregates as measured by CD. Depending on its degree of aggregation, this enzyme displayed between 50% and 100% helical structure, whereas a bacterial xylanase and a fungal polygalacturonase exhibited more beta-sheet structure. The polygalacturonase was apparently devoid of helical structure. PMID- 1903722 TI - Both D factor/LIF and IL-6 inhibit the differentiation of mouse teratocarcinoma F9 cells. AB - Differentiation-stimulating factor (D factor)/leukemia inhibitory factor (LIF) and IL-6 are reported to be cytokines having multifaced functions including the induction of differentiation in mouse myeloid leukemia M1 cells. We here report that both D factor/LIF and IL-6 inhibit the differentiation of mouse teratocarcinoma F9 cells induced by retinoic acid alone or combined with dibutyryl cAMP. From the microscopic observation as well as Northern blot analysis using cDNA probes encoding several marker proteins for differentiation of F9 cells, we concluded that D factor/LIF and IL-6 are functionally closely related in the induction of differentiation in M1 cells and in the inhibition of F9 differentiation. PMID- 1903723 TI - Blood loss and safety with desmopressin or placebo during aorto-iliac graft surgery. AB - In a double blind, placebo controlled study in 50 patients undergoing aorto-iliac graft surgery, we studied the effects of desmopressin given prior to surgery on blood loss and blood transfusion requirements. Desmopressin reduced the number of patients with clinically significant bleeding. Blood loss volumes and transfusion requirements were lower in the desmopressin group, but this could not be verified statistically. Even if our study population has a high incidence of generalised arteriosclerotic disease, there were no clinical manifestations of venous thromboembolism, no increase of graft occlusions and no myocardial infarction during the operative or early postoperative period. Desmopressin may be used in patients with excessive peroperative bleeding or a prolonged preoperative bleeding time. In patients where desmopressin is considered to be haemostatically efficacious, it may be used with a maintained margin of safety. PMID- 1903724 TI - Low dose follicle-stimulating hormone therapy for polycystic ovarian disease. PMID- 1903725 TI - Polycystic ovarian syndrome: safety and effectiveness of stepwise and low-dose administration of purified follicle-stimulating hormone. AB - OBJECTIVE: An attempt to induce ovulation with a single dominant follicle in polycystic ovarian syndrome (PCOS) patients. DESIGN: Comparing ultrasound and estradiol (E2) measurements during treatment with a low-dose protocol (using purified follicle-stimulating hormone, starting with 75 IU/d and increasing every 7 days by 37.5 IU/d) with those obtained following treatment with a conventional protocol using the same drug. SETTING: Specialist Reproductive Endocrine Unit. PATIENTS PARTICIPANTS: Eight PCOS patients of whom six had failed to respond adequately to the conventional protocol. MAIN OUTCOME MEASURE: Rate of cancellation of cycles, number of leading follicles, and serum E2 concentration at the time of ovulation. RESULTS: Treatment with the low-dose protocol resulted in a significant reduction in the number of leading follicles (P less than 0.04), serum E2 concentrations (P less than 0.0002), and a higher rate of ovulation. As a result, five patients conceived compared with none in the conventional protocol. CONCLUSION: Using the low-dose protocol permitted induction of ovulation safely and successfully in a selected group of PCOS patients who were previously difficult to treat with the conventional ovulation induction protocol. PMID- 1903727 TI - The luteal phase during gonadotropin therapy: effects of two human chorionic gonadotropin regimens. AB - OBJECTIVE: Luteal phase abnormalities are known to complicate ovulation induction with gonadotropins. This study was performed to test the effect of a modified human chorionic gonadotropin (hCG) regimen on the luteal phase during gonadotropin treatment. DESIGN: Fifteen women from a private practice setting volunteered to be studied during each of two nonconception, gonadotropin stimulated cycles. After ovarian stimulation with human menopausal gonadotropins (hMG), hCG was administered either as a single dose of 10,000 IU (single dose) or in two divided doses of 5,000 IU given 1 week apart (split dose). MAIN OUTCOME MEASURES: Early, midluteal, and late luteal estradiol (E2) and progesterone (P) levels and luteal phase lengths were measured, and their median values and intraquartile ranges (IQR) compared using nonparametric analysis. RESULTS: Early and midluteal E2 and P levels were similar regardless of which hCG regimen was administered. The median late luteal E2 level was 1,146.0 pg/mL (the IQR ranged from 633 to 1,650, IQR = 1,017) with the split-dose regimen and 240.0 pg/mL (the IQR ranged from 150 to 460, IQR = 310) with the single-dose regimen. The median late luteal P level was 108.0 ng/mL (the IQR ranged from 58.5 to 129, IQR = 70.5) with the split-dose regimen and 4.2 ng/mL (the IQR ranged from 1.9 to 11.7, IQR = 9.8) with the single-dose regimen. Median luteal phase lengths were 16 days (the IQR ranged from 15 to 17, IQR = 2) for the split-dose regimen and 11 days (the IQR ranged from 10 to 12, IQR = 2) for the single-dose regimen. CONCLUSION: In hMG-stimulated cycles, a second dose of hCG given during the midluteal phase significantly increases late luteal E2 and P levels and consistently lengthens the luteal phase. PMID- 1903726 TI - Clinical features and circulating gonadotropin, insulin, and androgen interactions in women with polycystic ovarian disease. AB - OBJECTIVE: To investigate the interactions of hyperinsulinemia and inappropriate gonadotropin secretion in women with polycystic ovarian disease (PCOD). DESIGN: Comparative study of endocrinologic parameters in subjects with PCOD. SETTING: Open patient clinic of reproductive endocrinology at University Central Hospital of Turku, Finland. PATIENTS: Fourteen nonobese and 10 obese patients with PCOD. Seven healthy women for reference data collection. Normal thyroid function, serum prolactin concentration, normal diurnal cortisol variation, euglycemia in all subjects. MAIN OUTCOME MEASURES: Serum concentrations of insulin, testosterone, androstenedione, dehydroepiandrosterone sulfate, sex hormone-binding globulin, immunoreactive luteinizing hormone (LH), bioactive LH, and follicle-stimulating hormone (FSH). RESULTS: The concentration of insulin was higher and that of bioactive LH was lower in obese than in nonobese PCOD women in whom the levels were also above the upper reference value. There was a negative correlation between insulin and bioactive LH levels (r = -0.57). Bioactive LH correlated inversely with the body mass index (BMI) (r = -0.50). After eliminating the effect of the BMI, the correlation between bioactive LH and insulin was no longer significant (r = -0.37). The bioactive LH and immunoreactive LH/FSH ratio correlated significantly (r = 0.68). CONCLUSIONS: These data demonstrate that hyperandrogenic women can be divided into two subgroups: those with insulin resistance, normal or minimally elevated LH, and markedly elevated insulin levels; and those with elevated LH levels, no insulin resistance, and normal insulin concentrations. Obesity is associated with the former, and high bioactive LH levels with the latter subgroup. PMID- 1903728 TI - Progesterone production in cultured human granulosa cells: correlation with follicular fluid hormone levels. AB - STUDY OBJECTIVE: To examine the progesterone (P) production by cultured granulosa cells and the hormonal content in the follicular fluid (FF) of ovarian hyperstimulated women. DESIGN: Retrospective. SETTING: Private Fertility Clinic and National Research Institute. PATIENTS: Eighteen patients undergoing in vitro fertilization or gamete intrafallopian transfer programs. RESULTS: Progesterone levels Measured in the culture medium of granulosa cells decreased sixfold with culture time. Human luteinizing hormone (LH) increased P production only when basal P production was less than 1 microgram/mL. Granulosa cell P production in culture was negatively correlated with FF LH-human chorionic gonadotropin (hCG) levels. Follicular fluid follicle-stimulating hormone (FSH) levels were positively correlated with FF P and 17 beta-estradiol (E2) concentrations. Similar results were found between FF LH (hCG) and E2 levels, but there was no relationship between FF LH (hCG) and FF P values. CONCLUSION: The high dose of hCG administered during gonadotropin treatment could induce a decrease in the in vitro granulosa cell P production. PMID- 1903729 TI - Differential responsiveness of luteinized human granulosa cells to gonadotropins and insulin-like growth factor I for induction of aromatase activity. AB - OBJECTIVE: To examine the in vitro responsiveness of cultured luteinized human granulosa cells over time to insulin-like growth factor 1 (IGF-1), human follicle stimulating hormone (FSH), and human chorionic gonadotropin (hCG) for the induction of aromatase activity. DESIGN: Granulosa cells were retrieved from preovulatory follicles in patients undergoing in vitro fertilization. Cells were cultured for a period of 72 hours or 10 days. The ability of hCG, human FSH, and/or IGF-I to induce aromatase activity was assayed by the stereospecific release of tritium from [1B-3H]androstenedione. RESULTS: Short-term cultures (72 hours) demonstrated a marked rise in aromatase activity in response to human FSH and IGF-I, whereas a smaller response to hCG was observed. In contrast, 10-day cultures demonstrated responsiveness predominantly to hCG rather than human FSH for the induction of aromatase activity with no remarkable effect of IGF-I. CONCLUSION: Luteinized human granulosa cells undergo a transformation from an initial human FSH and IGF-I responsive state to an hCG responsive state in long term cultures. PMID- 1903730 TI - Hepatic lipase activity during oral and parenteral 17 beta-estradiol replacement therapy: high-density lipoprotein increase may not be antiatherogenic. AB - OBJECTIVE: Hepatic lipase activity is involved in the removal of cholesterol and phospholipid from plasma high-density lipoprotein (HDL) to the liver. Changes in hepatic lipase are responsible for some lipoprotein modifications observed during estrogen administration (i.e., increased HDL levels). The aim of this study was to compare the effects of alternative routes of administration of estrogen on hepatic lipase activity and lipoprotein metabolism. DESIGN, PATIENTS: The effects of oral and parenteral estradiol (E2) replacement therapy on post-heparin hepatic lipase were studied in the short-term (6 weeks) in postmenopausal women. INTERVENTIONS: Ten patients received 2 mg/d or oral micronized E2 and 10 patients 3 mg/d of percutaneous E2. RESULTS: Both treatments significantly increased plasma E2 levels. Hepatic lipase decreased (-33%) significantly (P less than 0.05), and the phospholipids and free cholesterol content of HDL and HDL3 increased significantly (P less than 0.05) during oral but not during parenteral treatment. CONCLUSIONS: The short-term pharmacological effect of E2 on hepatic lipase depends on the route of administration. The inhibition of this enzyme may reduce the removal of HDL-cholesterol by the liver. The expected vascular benefits of such a pharmacological increase in HDL are questionable. PMID- 1903731 TI - Possible role of pure human follicle-stimulating hormone in the treatment of severe male-factor infertility by assisted reproduction: preliminary report. AB - OBJECTIVE: Experimental clinical trial assessing the potential of systemic follicle-stimulating hormone (FSH) to improve sperm fertilizing ability in in vitro fertilization (IVF). DESIGN: Retrospective clinical evaluation of severe male factor patients failing fertilization in IVF or showing severe sperm defects. SETTING: Academic tertiary clinical care unit. PATIENTS, PARTICIPANTS: Fourteen patients (41 cycles) who failed IVF, 22 patients (32 cycles) with severe quantitative and qualitative semen abnormalities indicating poor fertilization. INTERVENTIONS: TREATMENT: FSH 150 U IM three times a week for 3 months. MAIN OUTCOME MEASURE(S): Pretreatment and post-treatment evaluation of endocrine profile, basic semen analysis, and fertilization and pregnancy rates. HYPOTHESIS: FSH treatment may improve spermatogenesis quality by its multiple actions on the Sertoli-gamete cell compartment without interfering with testicular hormonogenic function. RESULTS: No significant changes were observed in the endocrine profile or in semen parameters; individual cases showed improvements in sperm concentration and motility. Significant increase in fertilization rate of preovulatory oocytes was demonstrated; seven term pregnancies were achieved. CONCLUSIONS: A multicenter randomized, double-blind trial with crossover is needed to demonstrate the benefit of systemic FSH administration and if this effect is FSH exclusive. PMID- 1903733 TI - Combined intrafallopian/intrauterine reduction of a quintuplet gestation. AB - We describe the first successful outcome of a case of combined tubal and intrauterine quadruplet pregnancy in the literature. The patient's risk factors for combined pregnancy included a history of PID as well as the use of hMG therapy. A laparoscopic salpingectomy was performed, followed by a multifetal pregnancy reduction procedure. Two healthy infants were delivered at 37 weeks of gestation. PMID- 1903732 TI - Prospective randomized study of human menotropin versus a follicular and a luteal phase gonadotropin-releasing hormone analog-human menotropin stimulation protocols for in vitro fertilization. AB - OBJECTIVE: To determine whether gonadotropin-releasing hormone analogs (GnRH-a) initiated either in the luteal phase or in the early follicular phase immediately preceding menotropin will improve the fertilization, implantation, and pregnancy rates (PR) in all IVF patients, when compared with menotropins alone. DESIGN: In a prospective, controlled, randomized study we compared a pure follicle stimulating hormone (FSH) human menopausal gonadotropin (hMG) protocol (group A = control) (n = 93 cycles) to two protocols in which GnRH-a pretreatment plus pure FSH and/or hMG was used in in vitro fertilization candidates. In group B (n = 64) GnRH-a was initiated during the luteal phase and in group C (n = 35) during the follicular phase. RESULTS: We found (1) no differences in fertilization and implantation rates between the three protocols; (2) similar pregnancy rates per transfer when similar number of conceptus were transferred (A = 30%, B = 22%, C = 21%); (3) an increase of the number of oocytes obtained; and (4) a reduction in the cancellation rate with both GnRH-a protocols. CONCLUSIONS: These findings suggest that there is no obvious superiority between the two GnRH-a protocols in the dosage schedule used and that the major advantage of GnRH-a over non-GnRH-a protocols is in decreasing the cancellation rate and increasing the number of oocytes and conceptus obtained. The follicular phase GnRH-a protocol required less hMG-pure FSH than the luteal phase GnRH-a protocol. PMID- 1903734 TI - Ovulation induction by step-down administration of purified urinary follicle stimulating hormone in patients with polycystic ovarian syndrome. AB - The step-down method can be an alternative method of ovulation induction in women with PCOS. This protocol can induce ovulation with a smaller dose of FSH and with lower incidence of excessive ovarian enlargement in comparison with the traditional fixed-dose administration method. PMID- 1903735 TI - Muscarinic acetylcholine receptors: structure and function. PMID- 1903736 TI - The development of insulin-dependent diabetes mellitus in non-obese diabetic mice: the role of CD4+ and CD8+ T cells. PMID- 1903737 TI - Effect of divalent metal cations on Rhizobium meliloti beta-galactosidase. PMID- 1903739 TI - Biosensors in organic phases. PMID- 1903738 TI - Properties and functions of the semicarbazide-sensitive amine oxidases. PMID- 1903740 TI - Plasmid maintenance alters substrate affinity. PMID- 1903741 TI - Urokinase-type plasminogen activator and its inhibitor PAI-1 in breast cancer: studies at both protein and mRNA level. PMID- 1903742 TI - Studies on the gene expression of several NADPH oxidase components. PMID- 1903743 TI - Development of a pressure transducer assay for monitoring the specific activity of hydrogenophilic methanogens. PMID- 1903744 TI - The prevalence of Mycoplasma pneumoniae in ambulatory patients with nonstreptococcal sore throat. AB - Several studies have implicated Mycoplasma pneumoniae as an important cause of nonstreptococcal pharyngitis in certain clinical settings. This study was performed to determine the prevalence of M. pneumoniae infection in family practice patients with sore throats and to identify patient characteristics predictive of this infection. M. pneumoniae throat cultures were obtained from 419 patients aged five years or older who were seen in one of four family practice offices with a complaint of sore throat. The overall prevalence of M. pneumoniae infection was 13%. It was characterized by more frequent hoarseness and less frequent complaint of postnasal drip when compared with other nonstreptococcal infections. Compared to patients with streptococcal pharyngitis, M. pneumoniae patients revealed a strikingly dissimilar clinical presentation. In particular, while pharyngitis is predictive of streptococcal infections, its presence did not predict M. pneumoniae infection. Recently developed rapid office based tests for M. pneumoniae may allow timely diagnosis of this common and formerly elusive pathogen. Further study is required to validate the utility of such methods and to evaluate the efficacy of treatment. PMID- 1903745 TI - Pyrimidine catabolism in Pseudomonas aeruginosa. AB - Pyrimidine catabolism in Pseudomonas aeruginosa was investigated. It was found that the pyrimidine bases uracil and thymidine as well as their respective reductive catabolic products could be utilized as sole sources of nitrogen. Reductive degradation of the pyrimidine bases was noted. The reductive catabolic pathway enzymes dihydropyrimidine dehydrogenase, dihydropyrimidinase and N carbamoyl-beta-alanine amidohydrolase were all detected in minimal medium grown cells. Induction of pyrimidine catabolism by uracil was observed in this pseudomonad. Pyrimidine degradation in P. aeruginosa was not subject to catabolite repression. PMID- 1903746 TI - Antibodies to listeriolysin O reflect the acquired resistance to Listeria monocytogenes in experimentally infected goats. AB - We induced experimental listeriosis in goats by two sequential oral inoculations of Listeria monocytogenes serovar 1/2a at 8 months' interval. Immunoblot analysis with the goat sera demonstrated listeriolysin O (LLO) as the principal protein antigen of L. monocytogenes. Pre-existing antibodies to LLO were, depending on their initial level, associated with either mild clinical symptoms of short duration or the total absence of clinical symptoms. Similarly, the presence and development of such antibodies corresponded with the disappearance pattern of L. monocytogenes from the gastrointestinal tract. These findings suggest that an association exists between antibodies to LLO and acquired resistance to Listeria infections. PMID- 1903747 TI - Cloning of the gene conferring resistance to mupirocin in Staphylococcus aureus. AB - A plasmid known to be associated with mupirocin resistance of Staphylococcus aureus has been isolated and a restriction enzyme map constructed. An EcoRI fragment of 4.05 kb from this plasmid has been cloned into an Escherichia coli Staphylococcus aureus shuttle vector and shown to carry the gene for resistance to mupirocin. The DNA sequence of a small section of the gene has been determined and the derived amino acid sequence compared with a data bank. The amino acid sequence is identical for eight amino acids with the sequence of isoleucyl tRNA synthetase of E. coli. This finding adds to the evidence that mupirocin resistance is the result of a modified isoleucyl tRNA synthetase. PMID- 1903748 TI - Expression in Caulobacter crescentus of the phosphate-starvation-inducible porin OprP of Pseudomonas aeruginosa. AB - The gene for the phosphate-starvation-inducible outer membrane protein OprP, of Pseudomonas aeruginosa was introduced into Caulobacter crescentus CB2A on a plasmid vector. As is the case in P. aeruginosa and Escherichia coli the oprP gene was inducible under conditions of limiting phosphate in C. crescentus. However, the maximal medium concentration of phosphate which still permitted induction of OprP was lower in C. crescentus (50 microM) than in P. aeruginosa (200 microM). Induction of OprP was coincident with the process of stalk elongation, known to occur in C. crescentus under phosphate starvation conditions. When induced, OprP was localized to the cell envelope and became a major membrane protein, indicating that the Pseudomonas promoter was efficiently recognized in C. crescentus and that the gene product was targeted to the appropriate region of the cell. Our data provide support for the hypothesis that the mechanism for regulation of phosphate-starvation-inducible genes is highly conserved amongst the eubacteria. PMID- 1903749 TI - Prochymosin expression in Bacillus subtilis. AB - Prochymosin (PC) sequence was cloned in Bacillus subtilis using two kinds of plasmid constructions. In plasmid pSM316 the cDNA was inserted to obtain the intracellular expression of the enzyme. The enzyme turned out to be expressed in an insoluble form which could be converted to native enzyme under proper denaturing and refolding conditions. The levels of intracellular expression of PC were further enhanced by modifying the 5' region of the gene in a way that a two cistron expression system was created. For the PC secretion, the cDNA was fused to the subtilisin leader sequence and expressed under the control of the B. subtilis neutral protease promoter. A properly folded PC was secreted by the cells, although to low levels. PMID- 1903750 TI - Analysis of Bordetella pertussis cya operon regulation by use of cya-lac fusions. AB - In Bordetella pertussis virulence-associated genes, including adenylate cyclase toxin (Cya), are coordinately regulated in response to environmental signals by proteins coded by the bvg-locus. We have constructed cya-lac fusions in Escherichia coli and have shown that the cya operon is not expressed in E. coli, neither is it activated by bvg, when introduced in trans. The cya-lac fusion is fully active when returned to B. pertussis by homologous recombination and responds to bvg-dependent activation and environmental regulation. These results indicate that in B. pertussis the activation of the cya operon by bvg is indirect. PMID- 1903751 TI - Cloning of a chromosomal alpha-amylase gene from Bacillus stearothermophilus. AB - We have cloned and sequenced a gene for a heat-stable alpha-amylase from a natural isolate of Bacillus stearothermophilus. Previously, it had been shown that B. stearothermophilus amylase genes may be harboured on indigenous plasmids. We have found that our isolate harbours the amylase gene only on the chromosome and not on its indigenous plasmid. PMID- 1903752 TI - Detection and purification of the free A subunit of heat-labile enterotoxin produced by enterotoxigenic Escherichia coli. AB - After removal of total B subunit and heat-labile enterotoxin (LT) from crude cell extracts of enterotoxigenic Escherichia coli (HB 101-EWD 299) by Bio-gel A 5 m column chromatography, the crude cell extract was shown to contain a free A subunit (A' subunit) that did not bind to the coligenoid of the B subunits. The A' subunit was found to be immunologically identical to the A subunit of holo-LT and was purified to show only one band in SDS-poly-acrylamide gel electrophoresis (PAGE). The mobility of the A' subunit was identical to that of the A subunit of holo-LT. The pI value of the A' subunit was also the same as that of the A subunit of holo-LT. These data suggest that in enterotoxigenic E. coli there is free A subunit which may be involved in formation of holo-LT, analogously to free B subunit (coligenoid), and that the free A subunit is physicochemically and immunologically identical to the A subunit of holo-LT. PMID- 1903753 TI - Formation of glycoprotein degrading enzymes by Bacteroides fragilis. AB - Bacteroides fragilis NCDO 2217 produced a wide range of cell-associated hydrolytic enzymes (neuraminidase, alpha-fucosidase, alpha-N acetylgalactosaminidase, beta-galactosidase, beta-N-acetylglucosaminidase) that could potentially degrade the carbohydrate moieties of mucin, a complex glycoprotein. The type of substrate used for growth markedly influenced their formation in batch cultures. Synthesis of neuraminidase, alpha-fucosidase, alpha N-acetylgalactosaminidase and to a lesser extent, beta-N-acetylglucosaminidase, was inversely related to growth rate in continuous cultures (D = 0.03 h-1-0.23 h 1) in which porcine gastric mucin provided the sole source of carbon and nitrogen. PMID- 1903754 TI - Effects of salt concentration on bacterial growth on plates with gradients of pH and temperature. AB - A temperature gradient device has been used to produce pH-temperature gradient plates. The response of Salmonella typhimurium and Bacillus cereus to continuous gradients of pH and temperature has been mapped. A third variable, sodium chloride, was investigated by incorporating it at different concentrations in a series of gradient plates. Both organisms exhibited an optimum temperature and pH range for maximum salt tolerance. PMID- 1903755 TI - Health service delivery and research outcomes of a common departmental structure for psychiatric consultation-liaison and social work services at a university hospital. AB - Convincing evidence exists that psychosocial factors have a major impact on both outcome and costs in the medical/surgical services in general hospitals. This paper describes the Human Services Department's impact on social work and consultation-liaison psychiatry, using a data-based management system across five specialties: 1) social work; 2) consultation-liaison psychiatry; 3) supportive care (hospice); 4) home care (home health discharge planning); and 5) pastoral care, which offers opportunities for research and quality assurance monitoring. Time spent in service delivery was used to estimate the cost per hour: 1) pastoral care $96; 2) social work $36; 3) consultation-liaison psychiatry $59; 4) home care $49. Referral to social work was preferred for a range of family and discharge planning services. Consultation-liaison services were preferred for depression, paranoid behavior, and management problems. Referral overlap was noted for "coping with diagnosis" for social work and consultation-liaison psychiatry. Using a computerized data base format for documenting the referral process, work accomplished, and time spent among those services providing mental health care in the general hospital permits the observation of redundancy of services delivered and their costs. PMID- 1903756 TI - [Distribution of ABO, MN, Rh blood groups and Hp, Tr, Gc and C3 serum factors in the Buryat population]. AB - Polymorphism of blood groups ABO, MN, Rh and serum proteins Hp, Tf, Gc, C3 was studied in Buryat populations of Zabaikalie, Pribaikalie, Olkhon island. No indication of significant heterogeneity was observed. Gene frequencies varied in different systems within the ranges: ABO (p-0.142-0.183; q-0.205-0.324; r-0.567 0.630); MN (m-0.531-0.624), Rh(d) (0-0.214), Hp (Hp 1-0.268-0.339), C3 (C3F-0.023 0.090), Tf (TfC-0.971-1.0), Gc (Gc1-0.728-0.840). Genetic distances between main Buryat groups were estimated. PMID- 1903757 TI - [Cloning and cytogenetic localization of evolutionarily conserved genomic sequences which are expressed in the head of the Drosophila melanogaster imago]. AB - Screening of Drosophila melanogaster genomic library was carried out using mouse brain polysomal poly(A)+RNA. As a result, 100 clones were selected, among which 14 clones were picked up after hybridization with fly head poly(A)+RNA. It follows therefore, that these clones contain evolutionary conserved sequences which are expressed in Drosophila fly heads. Analysis of these 14 clones revealed RNA-coding fragments. Comparison of their expression in heads and bodies of Drosophila was carried out. Using in situ hybridization we determined the localization of selected 14 sequences on polytene chromosomes. The possibility of further analysis of some clones to study developmental and functional processes in neural system of Drosophila is discussed. PMID- 1903758 TI - [Cytogenetic analysis of chromosome segments containing radiosensitivity genes in Drosophila. Radiation mutagenesis in the 44-45 region of chromosome 2 of Drosophila melanogaster]. AB - The first step of cytogenetic analysis of Drosophila melanogaster chromosome 2 44F-45D containing the radiosensitivity gene rad(2)201 is described. Using various mutation selection systems as well as lines of different origin and two kinds of ionizing radiation--gamma-rays and neutrons--the mutagenesis in the region of interest is characterized at the cytogenetic level. 85 gamma-induced mutations affecting viability were isolated in the 44F 2-4; 45C6-7 interval, 27% of mutations being chromosomal aberrations. 15 radiation-induced aberrations were obtained by selecting mutations at the white gene inserted into the 45D region by P-mediated transformation. The 44F-45D region is characterized by relatively low frequency of deficiency formation and by significant predomination of heterochromatic aberrations in the spectrum of rearrangements. In these regions, the existence of hot spots for heterochromatic aberrations was discovered. As low deletion frequency is not connected with the presence of haplolethal and haplosterile loci in the region studied, the unusual character of radiation mutagenesis reflects possibly the peculiarities in sequence organization of the chromosomal region mentioned or the packaging in the sperm nuclei. PMID- 1903759 TI - Magnetic resonance imaging of the calcaneus: normal anatomy and application in calcaneal fractures. AB - Images obtained from normal volunteers demonstrate highly detailed anatomy of the soft tissue and bony structures near the calcaneus and subtalar joint. Cortical bone, marrow, articular cartilage, ligaments, tendons, muscles, fibrous tissue, vascular bundles, and nerves can be identified. However, images obtained of acute calcaneal fractures were found to offer unsatisfactory depiction of bony anatomy. The presence of small fragments was obscured by a change in normal marrow signal by contusion, hemorrhage, and edema, and by the inability of magnetic resonance (MR) to image small pieces of cortical bone. Only in rare instances might MR be helpful in the acute setting when the location or displacement of tendons cannot be clearly ascertained with computed tomography (CT). MR may prove more useful in the long-term follow-up of healed fractures with persistent pain. In this setting it might be used in the diagnosis of complications such as residual or recurrent tendon displacement, tenosynovitis, heel fat integrity, and tarsal tunnel evaluation. However, this paper did not directly compare the efficacy of MR with that of CT in the long term. Therefore, the degree to which MR may eventually supplement or supplant CT is unclear and further study is required before the use of MR can be recommended in the routine clinical follow-up of calcaneal fractures. PMID- 1903760 TI - Carrier detection in haemophilia A by direct analysis of factor VIII gene lesions. AB - CGA----TGA (Arg----Term) transitions in the factor VIII gene causing severe haemophilia A were detected in two patients at codons 336 and 427 using a combination of oligonucleotide discrimination hybridization and DNA sequencing. Carrier detection analysis was then performed by polymerase chain reaction/direct sequencing of the appropriate region of the gene in female relatives of the probands. PMID- 1903761 TI - A serine-to-arginine (AGT-to-CGT) mutation in codon 549 of the CFTR gene in an Italian patient with severe cystic fibrosis. PMID- 1903762 TI - Monoclonal anti-VH141 antibodies that specifically recognize the heavy chain variable region of, and are closely related to, MOPC141 myeloma protein whose VH gene belongs to VHQ52 family. AB - To raise monoclonal antibodies that specifically recognize the heavy chain variable region of MOPC141 myeloma protein (VH141), which belongs to VHQ52 family, rats were immunized with Fd'-conjugated keyhole limpet haemocyanin (KLH) (Fd': Fd' fragments of MOPC141), and the spleen cells were fused with mouse myeloma cells. The resulting 900 hybridomas were screened for antibody activity against Fd'1 fragments having no constant H-chain sequences, which were prepared by cleavage of the Fd' fragments with cyanogen bromide, and two monoclonal antibodies, designated 3-2-7h and 3-5-6f, were obtained. Radioimmunoassay inhibition test showed that the two monoclonal antibodies specifically recognized the VH141, but each was directed to a different determinant on the VH141. When the functional VH gene of Abelson virus-transformed mu-producing pre-B cells, which could be strongly stained with 3-5-6f monoclonal antibody, was cloned and sequenced, the VH gene was closely relate to that of MOPC141 (88% and 94% homology at amino acid and DNA level, respectively). Taken together, the results indicated that 3-2-7h had high specificity only for the VH141, whereas 3-5-6f specifically reacted not only with the VH141 but also with the VH region closely related to that of MOPC141, and that both the monoclonal anti-VH141 antibodies were specific for a limited range of VH regions within the VHQ52 family rather than being VHQ52 family specific. These monoclonal anti-VH141 antibodies should be very useful to determine at a single cell level by immunofluorescence the usage of the VH gene(s) identical or closely related to that of MOPC141 during early B-cell development. PMID- 1903763 TI - Blot-sequencing of antibodies: application to analysis of V gene usage among anti steroid monoclonal antibodies. AB - Automated gas-phase protein sequencing has been used to characterize variable regions of antibody heavy and light chains separated by SDS-polyacrylamide gel electrophoresis (PAGE) and electroblotted onto Immobilon polyvinylidene difluoride membranes ('blot-sequencing'). Starting from 100 micrograms of antibody, 20 or more residues of N-terminal VH and VL sequences can regularly be obtained, which is often sufficient to assign the V region to a known family or subgroup. We have applied the blot-sequencing method to analysis of VH and VL usage among a panel of monoclonal anti-steroid antibodies, namely anti progesterone, anti-pregnanediol, anti-estrone and anti-testosterone. The results demonstrate restricted, repetitive usage of VL subgroups and VH families related to anti-steroid specificities. VL regions of the VK1 group were particularly associated with anti-progesterone, VK21 with anti-estrone, and VK8 and VK9 with anti-pregnanediol. VH regions of anti-progesterone antibodies were all derived from the VHVGAM3.8 family; anti-estrone and anti-pregnanediol antibodies were derived from the VH7183 and VH36-60 families. The latter two families appear to characterize antibodies raised against steroids conjugated to proteins via a sugar bridge. Differences in VH/VL combination were associated with diversity of antibody specificity. In order to extend the sequence data obtained by this technique and confirm family assignments, we have shown that internal V-region sequences can be obtained by limited chemical cleavage of whole antibody with cyanogen bromide, followed by separation of individual fragments by SDS-PAGE and blot-sequencing. PMID- 1903764 TI - Expression of MHC class II (Ia) antigen by the neonatal enterocyte: the effect of treatment with interferon-gamma. AB - Immunohistochemical techniques were used to probe the expression and inducibility of class II major histocompatibility complex (MHC) (Ia) antigens by the mouse enterocyte at various stages postpartum. Expression of Ia was related to both age and intestinal location. Ia antigen was not detected until at least 1 week post weaning and was noted thereafter in both proximal and distal intestine. Both crypt and villus enterocytes were stained in the distal small intestine, but staining was restricted to the upper portion of the villus in the proximal small intestine. Moreover, the extent of staining and the intensity of staining were greater in the distal small intestine. The effect of a single injection of recombinant mouse interferon-gamma (IFN-gamma) on Ia expression by enterocytes of 16-day-old, suckling BDF1 mice was examined. Injection of distilled water (DW) or 1 to 2 x 10(4) U IFN-gamma did not induce enterocyte Ia expression. Doses of 4-10 x 10(4) U were effective inducers of Ia on crypt and, occasionally, on lower villus cells examined 24 hr later. Staining did not persist on the enterocyte beyond 48 hr. In conclusion, Ia is not normally expressed on small intestinal enterocytes of the mouse until after weaning; however, Ia expression can be induced earlier by treatment with IFN-gamma. It is not known whether failure to detect Ia expression prior to weaning reflects a lack of positive stimuli and/or the presence of inhibitory stimuli, possibly carried in the breast milk. PMID- 1903765 TI - Cellular immune responses to the murine nematode parasite Trichuris muris. I. Differential cytokine production during acute or chronic infection. AB - A variety of T-cell parameters have been analysed in two H-2 compatible strains of mice, B10.BR and BALB/K, which differ in an absolute fashion in their ability to resist infection with the parasitic nematode Trichuris muris: BALB/K mice expel T. muris relatively rapidly, whereas B10.BR mice are unable to expel the parasite before the infection reaches patency. Analysis of Th1- and Th2-specific cytokines (IFN-gamma and IL-5, respectively) produced by in vitro Con A stimulated mesenteric lymph node cells (MLNC) from infected and normal mice demonstrated that MLNC from resistant BALB/K mice produced high levels of IL-5 and low levels of IFN-gamma whilst B10.BR MLNC secreted large amounts of IFN gamma in the relative absence of IL-5. As an in vivo correlate of in vitro IL-5 production, peripheral and tissue eosinophilia were quantified during the course of infection in the two strains of mice. No peripheral eosinophilia was observed in BALB/K or B10.BR individuals. However, a considerable intestinal eosinophilia was seen in the high IL-5-producing BALB/K mice compared to normal levels. Differences observed in cytokine profiles were not due to differential changes in the numbers of T cells within the MLN. Indeed, FACS analysis revealed a decrease in the relative percentage of CD4+ and CD8+ T cells in both strains of mice post infection. Our results suggest that resistance to T. muris involves the preferential induction of Th cells which secrete IL-5, whilst cells of a different Th subset (IFN-gamma producing) predominate in chronically infected mice. As such, this represents the first description of a correlation between the reciprocal activation of Th cell subsets in relation to acute or chronic intestinal infection with the same parasite in the same host species. PMID- 1903766 TI - Failure of a tumour to prime CTL specific for some of the minor H antigens it expresses but not others. AB - The H-Y-expressing murine tumour, ET-5, specifically immunizes B6 female mice that have rejected it against H-Y-positive male skin grafts, yet fails to prime their spleen cells for the generation of H-Y-specific cytotoxic T lymphocytes (CTL). ET-5 also fails to prime relevant congenic hosts to generate CTL specific for H-3 or H-25 minor H antigens, or major histocompatibility complex (MHC) class I antigens, all of which are expressed in immunogenic form by ET-5. Nonetheless, C3H.SW mice, which are MHC-compatible with B6 mice in which ET-5 originated, but differ from B6 at many minor H loci, can be primed to generate CTL directed against one or more unidentified minor H antigens. These CTL are conventional MHC restricted, CD8+ T cells, and require priming in vivo for their generation. Significantly, C3H.SW females can be primed by ET-5 to generate B6-specific CTL, but not H-Y-specific CTL. Thus CTL priming is selective in the sense that ET-5 primes CTL specific for some of the antigens it expresses but not others. The basis for this selectivity is not known but, in the case of H-Y antigen, it appears not to result from an inability of ET-5 to express either H-2Db-encoded antigens, the restriction element for H-Y-specific CTL in B6 females, or H-Y itself in vivo. PMID- 1903767 TI - Enzymatically deacylated Neisseria lipopolysaccharide (LPS) inhibits murine splenocyte mitogenesis induced by LPS. AB - Acyloxyacyl hydrolase is a leukocyte enzyme that selectively removes the secondary acyl chains from the lipid A moiety of gram-negative bacterial lipopolysaccharides (LPS). As predicted by the reported contribution of secondary acyl chains to the bioactivities of lipid A analogs, enzymatic deacylation of Salmonella typhimurium Rc LPS substantially reduces its potency in the dermal Shwartzman reaction and in several in vitro assays that measure responses of human endothelial cells and neutrophils, whereas the potency of this LPS for inducing murine splenocyte mitogenesis is affected much less. In the experiments described here, we studied the impact of acyloxyacyl hydrolysis on the bioactivities of several LPS that differ from Salmonella LPS in carbohydrate and lipid A structures. Deacylated LPS from Escherichia coli, Haemophilus influenzae, Neisseria meningitidis, and S. typhimurium were similarly reduced in potency in the Limulus lysate test (30- to 60-fold reduction in potency relative to the corresponding mock-treated LPS), and the ability of all of these deacylated LPS to stimulate neutrophil adherence to human endothelial cells was reduced by a factor of 100 or more. For LPS from E. coli, H. influenzae, and Pseudomonas aeruginosa, the impact of deacylation on spleen cell mitogenesis was also similar to that observed for S. typhimurium LPS: deacylation reduced potency by less than 15-fold. Unexpectedly, the potency of Neisseria LPS in the murine splenocyte mitogenicity test was reduced over 100-fold by deacylation, and deacylated Neisseria LPS could block the mitogenic activity of Neisseria and Salmonella LPS. These studies indicate that the contribution of secondary acyl chains to the bioactivities of a given LPS cannot be predicted with confidence from the reported structure-activity relationships of lipid A or from the behavior of other deacylated LPS. PMID- 1903768 TI - Proteins released from Mycobacterium tuberculosis during growth. AB - Proteins secreted from Mycobacterium tuberculosis during growth are believed to be important for protective immunity against tuberculosis. We have investigated the growth of M. tuberculosis in an enriched liquid medium. The release of isocitrate dehydrogenase from the bacilli served as a marker of autolysis and was observed during the late logarithmic growth phase. The release of proteins during the culture period was investigated by enzyme-linked immunosorbent assay and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Three major groups of proteins, which differed markedly with respect to profile of release and location in intact bacilli, were defined. A short-term filtrate devoid of autolytic products was defined and found to be composed of 33 major components. Five proteins were identified by monoclonal antibodies. Pronounced superoxide dismutase activity was detected in the filtrate. The enzyme was purified and identified as a dominating component of short-term filtrate. PMID- 1903769 TI - Protection against anthrax with recombinant virus-expressed protective antigen in experimental animals. AB - We previously described the cloning and expression of the protective antigen (PA) gene of Bacillus anthracis in both vaccinia virus and a baculovirus. The antigenicity of the PA products was characterized. PA expressed by the recombinant vaccinia viruses elicited a partial protective immune response against a lethal B. anthracis spore challenge in guinea pigs and mice. The WR strain vaccinia virus recombinant (WR-PA) protected 60% of male mice and 50% of guinea pigs. WR-PA elicited high anti-PA antibody titers in mice but not in guinea pigs. Connaught strain vaccinia virus recombinants failed to protect any immunized animals. PA purified from baculovirus recombinant-infected cultures plus adjuvant partially protected male CBA/J mice and completely protected female Hartley guinea pigs from challenge. Both the recombinant and nonrecombinant PA preparations combined with adjuvant elicited high anti-PA antibody titers in Hartley guinea pigs and CBA/J mice. These data demonstrate that the recombinant baculovirus- and vaccinia virus-produced PAs were immunogenic in both guinea pigs and mice, that the baculovirus-PA recombinant was a useful source of immunogenic PA, and that vaccinia virus-PA recombinants may be feasible live anthrax vaccine candidates worthy of consideration for further development as live vaccines. PMID- 1903770 TI - Serum antibody response to Pseudomonas aeruginosa antigens during corneal infection. AB - Previous studies in our laboratory have indicated that naturally resistant, inbred DBA/2J mice mount a greater serum antibody response to Pseudomonas aeruginosa 19660 than susceptible C57BL/6J mice. However, the specificity of the antibody produced was not known. The present study examines the specificity and kinetics of the humoral response of these mouse strains to potential virulence factors produced by the organism during both a primary and a secondary corneal infection administered 4 weeks after the primary infection. Serum antibody levels specific for lipopolysaccharide (LPS), exotoxin A, phospholipase C (PLC), alkaline protease, elastase, and flagella were measured by enzyme-linked immunosorbent assay. Little or no antibody to either alkaline protease or elastase was detected during either primary or secondary infection. Immunoglobulin G (IgG) antibodies specific to exotoxin A, PLC, and flagella were detected 2 weeks after primary infection, and a rapid response to these antigens was measured 1 week after secondary infection. During primary infection, detectable LPS-specific antibody was only IgM, while IgG appeared only after secondary infection. The kinetics of the humoral response in susceptible C57BL/6J mice were similar to those in resistant DBA/2J mice, although the magnitude of the response varied according to the antigen tested. These results indicate that LPS, exotoxin A, PLC, and flagella are present or produced in amounts that are immunogenic during corneal infection by P. aeruginosa 19660 in the mouse strains tested. PMID- 1903771 TI - Memory T cell-mediated resistance to Mycobacterium tuberculosis infection in innately susceptible and resistant mice. AB - The memory T cell immune response to Mycobacterium tuberculosis infection was examined in strains of mice which vary in their natural susceptibility to Mycobacterium bovis BCG infection. Naturally susceptible (NS) C57BL/6 and naturally resistant (NR) B6D2 F1 hybrid mice were infected with a sublethal dose of M. tuberculosis and then given antibiotic therapy beginning 2 weeks postinfection. T cells from both strains of mice transferred significant levels of resistance to syngeneic mice challenged aerogenically with M. tuberculosis. This memory response was not substantially reduced by depletion of either L3T4+ or Lyt2+ T cells from the donor mice but was ablated by depletion of both T cell subsets. Cyclophosphamide pretreatment of C57BL/6 memory T cell donors also ablated the resistance transferred to recipient mice. In contrast, B6D2 memory T cells were not affected by cyclophosphamide treatment, suggesting that differences may exist in the metabolic state of the memory T cells in the two donor strains, despite the fact that they both develop similar levels of acquired resistance to a subsequent tuberculous challenge. PMID- 1903772 TI - Modulation of experimental autoimmunity: treatment of adjuvant arthritis by immunization with a recombinant vaccinia virus. AB - Live recombinant vaccinia viruses, expressing antigens from pathogenic microorganisms, are studied for their use as vaccines designed for the protection against infectious diseases. Infections with these vaccinia virus recombinants, expressing proteins or epitopes from viruses, parasites, or bacteria, have resulted in the development of specific neutralizing antibodies or cytotoxic T lymphocytes. Here, we describe the generation of a recombinant vaccinia virus expressing the mycobacterial 65-kDa heat shock protein (HSP65). A vaccinia recombinant virus was constructed by placing the gene for the Mycobacterium bovis BCG HSP65 under control of a vaccinia virus promoter and inserting this mycobacterial gene in the thymidine kinase locus of the vaccinia virus genome. Mycobacterial HSP65 is a critical antigen in the autoimmune model of adjuvant arthritis induced in Lewis rats by the immunization with Mycobacterium tuberculosis. We report the induction of immunity directed to this mycobacterial HSP65 by testing for the presence of specific antibodies and T-cell proliferation. Furthermore, induction of such immunity resulted in a reduction of arthritis severity when given to rats before or, even more interestingly, during development of arthritis. Disease reduction was not found after administration of HSP65 in the absence of vaccinia virus as a vector when given during arthritis development. Therefore, recombinant vaccinia virus may offer new prospectives for specific intervention in autoimmunity. PMID- 1903773 TI - The carboxyl-terminal region of staphylococcal enterotoxin type A is required for a fully active molecule. AB - Staphylococcal enterotoxin type A (SEA) gene (sea+) mutations were constructed by exonuclease III digestion or cassette mutagenesis. Five different sea mutations that had 1, 3, 7, 39, and 65 codons deleted from the 3' end of sea+ were identified and confirmed by restriction enzyme and nucleotide sequence analyses. Each of these sea mutations was constructed in Escherichia coli and transferred to Staphylococcus aureus by using the plasmid vector pC194. Culture supernatants from the parent S. aureus strain that lacked an enterotoxin gene (negative controls) and from derivatives that contained either sea+ (positive control) or a sea mutation were examined for in vitro sensitivity to degradation by monkey stomach lavage fluid, the ability to cause emesis when administered by an intragastric route to rhesus monkeys, and the ability to induce T-cell proliferation and by Western immunoblot analysis and a gel double-diffusion assay with polyclonal antibodies prepared against SEA. Altered SEAs corresponding to the predicted sizes were visualized by Western blot analysis of culture supernatants for each of the staphylococcal derivatives that contained a sea mutation. The altered SEA that lacked the C-terminal amino acid residue behaved like SEA in all of the assays performed. The altered SEA that lacked the three C terminal residues of SEA caused T-cell proliferation but was not emetic; this altered SEA was degraded in vitro by monkey stomach lavage fluid and did not reach in the gel double diffusion assay. Altered SEAs that lacked 7, 39, or 65 carboxyl-terminal residues were degraded by stomach lavage fluid in vitro, did not produce an emetic response, and did not induce T-cell proliferation or form a visible reaction in the gel double-diffusion assay. PMID- 1903774 TI - Pseudomonas aeruginosa variants isolated from patients with cystic fibrosis are killed by a bactericidal protein from human polymorphonuclear leukocytes. AB - The susceptibility of paired mucoid and nonmucoid variants of Pseudomonas aeruginosa isolated from 13 patients with cystic fibrosis (CF) to killing by a 55,000-Da bactericidal protein (BP55) from human polymorphonuclear leukocytes was studied. Mucoid and nonmucoid variants were equally sensitive to killing by BP55 at both pH 5.6 and pH 7.2. Eleven of the isolates were resistant to the bactericidal activity of 10% normal human serum but were as sensitive as the serum-sensitive isolates to BP55. Similarly, the 15 isolates with lipopolysaccharides (LPS) containing O-polysaccharide side chains (smooth LPS) were as sensitive to BP55 as those isolates with rough LPS.P. aeruginosa isolates from patients in poor clinical condition were more likely to have LPS of the smooth type and to be resistant to killing by 10% human serum than the isolates from patients in good clinical condition. We have concluded that the susceptibility of the P. aeruginosa isolates from patients with CF to killing by BP55 does not correlate with mucoid or nonmucoid variations, with the presence or absence of smooth LPS, or with the sensitivity or resistance to killing by normal human serum. PMID- 1903777 TI - Economic evaluation of neonatal intensive care. Which variables have to be known? PMID- 1903776 TI - The use of mupirocin before skin surgery. AB - Presumed skin cancers were excised from 46 consecutive outpatients without antibiotic cover. A purulent wound developed in ten patients. Similar, but contaminated lesions were excised from 40 patients, but mupirocin ointment was used before surgery. Not one purulent wound developed out of 45 excisions. PMID- 1903775 TI - Shift of excretory-secretory immunogens of Trypanosoma cruzi during human Chagas' disease. AB - We studied secreted-excreted immunogens in human patients infected with Trypanosoma cruzi. A pair of 45- to 55-kDa antigens and a family of shed acute phase antigens characterized the acute phase, while antibodies against a 160- to 170-kDa immunogen appeared at the chronic phase of the disease. PMID- 1903778 TI - What is the actual cost of neonatal intensive care? PMID- 1903779 TI - [Chief symptoms: bone pain and muscle weakness]. PMID- 1903780 TI - Is a decision to forgo tube feeding for another a decision to kill? PMID- 1903781 TI - Is a decision to forgo tube feeding for another a decision to kill? PMID- 1903782 TI - Cruzan v. Director, Missouri Dept. of Health. PMID- 1903783 TI - In re Estate of Sidney Greenspan. PMID- 1903784 TI - Westhart v. Mule. PMID- 1903785 TI - Phase I study of concurrent carboplatin and radiotherapy in previously untreated patients with stage III and IV head and neck cancer. AB - This study evaluated the toxicity resulting from combined therapy using carboplatin and radiotherapy in 22 patients with locally advanced (stage III and IV) head and neck cancer. Carboplatin was given after radiotherapy during the first 5 consecutive days of a 16-fraction course of radiotherapy delivered in a total of 22 days. To find the acceptable toxic dose of carboplatin, the patients were treated in groups of 3 patients each. The first group received 50 mg/m2 carboplatin and the dose was increased by 10 mg/m2 in each subsequent group. Unacceptable toxicity (severe mucositis, nausea and vomiting, and/or myelosuppression) was encountered at a carboplatin dose of 80 mg/m2. A further 10 patients were then treated at a dose of 70 mg/m2. At this dose toxicity was acceptable. Although the group of 22 patients is too small for response and survival data to be meaningful, 10 complete responses were seen and median survival is in excess of 67 weeks. PMID- 1903786 TI - Suppression of virulence factors of Pseudomonas aeruginosa by erythromycin. AB - The effects of erythromycin stearate over a concentration range of 0.1-10 mg/l on production of elastase, protease and leucocidin by clinical isolates of Pseudomonas aeruginosa were investigated. Growth of P. aeruginosa N42 in broth was not affected significantly during 24 h culture with erythromycin (0.1-10 mg/l), although extracellular protein contents were reduced by erythromycin at concentrations of 0.1-1.0 mg/l. Production of elastase and protease by strain N42 was significantly suppressed by erythromycin with a maximum inhibition at 0.5 mg/l, but the complete inhibition of enzyme production was not achieved. In contrast, leucocidin production by strain N42 was completely impaired by erythromycin at concentrations of 0.1-5.0 mg/l. Although the leucotoxic activity, as determined by vital staining, was not detected, the leucocidin fraction prepared from the autolysate of strain N42 cultured with 10 mg/l of erythromycin induced morphological changes in human leucocytes, resulting in release of elastase. Erythromycin exerted similar effects on other clinical isolates of P. aeruginosa. These findings indicate that erythromycin might have a role in P. aeruginosa infection, although it has no direct antibacterial activity. PMID- 1903787 TI - The diffusion of beta-lactam antibiotics through mixed gels of cystic fibrosis derived mucin and Pseudomonas aeruginosa alginate. AB - The rates of diffusion through purified extracellular alginate from Pseudomonas aeruginosa were measured for twelve beta-lactam antibiotics. The diffusion rate was reduced as the antibiotic molecular weight increased, but the range of diffusion rates exhibited by a common anti-pseudomonal penicillins was relatively small. The diffusion of ticarcillin through 1.0% w/v mixtures of alginate and purified mucus glycoprotein (mucin) from sputa of cystic fibrosis patients showed that, at equivalent concentrations, alginate represented the greater barrier to penetration. However if the mucin concentration was increased to 4.0% w/v, a more realistic physiological concentration, the diffusion of ticarcillin was retarded to a greater extent than in 1% w/v alginate, and the effect was compounded by other sputum components such as DNA. The results suggest that the antibiotic diffusion barrier represented by mucin may be significant in vitro, particularly for nebulized antibiotics. PMID- 1903789 TI - Effect of oral spiramycin on the faecal and oral bacteria in human volunteers. AB - Six healthy adult volunteers were treated with 1 g of oral spiramycin twice daily for five days, and their oral and faecal microbial flora were studied. Mean saliva and serum concentrations of the antibiotic never exceeded 2.1 +/- 1.1 mg/l. The number of volunteers whose oral cavity was colonized by Enterobacteriaceae, group D streptococci, staphylococci, and fungi remained unchanged following treatment. The mean count of anaerobic faecal bacteria was 10.3 +/- 0.6 log10 cfu/g initially. This did not change significantly during the treatment, nor did the composition of the predominant anaerobic flora. Mean counts of group D streptococci were 1000 times lower than those of anaerobes before treatment, and also remained unchanged during therapy. No overgrowth of fungi, staphylococci, or Pseudomonas aeruginosa was observed. No significant modifications occurred in the mean total count of faecal Enterobacteriaceae (7.9 +/- 0.4 versus 7.4 +/- 1.0 log10 cfu/g of faeces before and during treatment respectively). However, faecal concentrations of highly spiramycin-resistant Enterobacteriaceae (MIC greater than or equal to 512 mg/l) increased from 4.8 +/- 1.2 to 7.0 +/- 1.8 log10 cfu/g during treatment. The MIC50 value of spiramycin for anaerobes, Enterobacteriaceae, and group D streptococci were 0.125, 64, and 0.5 mg/l respectively before treatment, and these increased to 1024, 512 and 1024 mg/l respectively during treatment. This was attributed to the rise in the faecal concentrations of spiramycin, which reached 689 +/- 48 micrograms/g of faeces on the fifth day of treatment. These concentrations decreased rapidly on cessation of treatment. PMID- 1903788 TI - In-vitro activity of cefprozil (BMY 28100) and loracarbef (LY 163892) against pathogens obtained from middle ear fluid. AB - We compared the in-vitro activities of cefprozil, a novel oral cephalosporin, and of loracarbef, a new oral carbacephem, with other agents against middle ear fluid isolates obtained from children with acute otitis media. These included Streptococcus pneumoniae, Haemophilus influenzae and Branhamella catarrhalis. Cefprozil activity (MIC50 and MIC90) against S. pneumoniae was 0.25 and 0.50 mg/l; against H. influenzae 8 and 16 mg/l; against B. catarrhalis 2 and 2 mg/l. Loracarbef activity (MIC50 and MIC90) against S. pneumoniae was 1 and 2 mg/l; against H. influenzae 8 and 16 mg/l; against B. catarrhalis 1 and 8 mg/l. Cefprozil was four-fold more active against S. pneumoniae than loracarbef but similar to amoxycillin, amoxycillin/clavulanate, cefaclor, cefixime, cefuroxime and trimethoprim/sulfamethoxazole (TMP/SMX). Against H. influenzae, cefprozil was similar to loracarbef and other agents through less active than TMP/SMX and cefixime. Against B. catarrhalis, cefprozil was four-fold more active than loracarbef, cefaclor and cefixime but similar to the comparative antibiotics. Cefprozil and loracarbef activities were unaffected at pH 6 and 8 or in the presence of human serum, but there was a major diminution of activity for both agents at pH 5 and at inoculum sizes greater than or equal to 10(7) cfu/ml. Cefoprozil and loracarbef have consistent activity against middle ear pathogens and further pharmacokinetic and clinical studies appear warranted. PMID- 1903790 TI - Autism and tuberous sclerosis. PMID- 1903791 TI - Analyzing the substrate specificity of Saccharomyces cerevisiae myristoyl CoA:protein N-myristoyltransferase by co-expressing it with mammalian G protein alpha subunits in Escherichia coli. AB - A dual plasmid system was used to examine the protein and acyl-CoA specificities of Saccharomyces cerevisiae myristoyl-CoA:protein N-myristoyltransferase (NMT) by co-expressing it in Escherichia coli with each of four homologous alpha subunits of the signal-transducing, heterotrimeric G proteins. Exogenous [3H]myristate was incorporated into rat Gi alpha 1 and rat Go alpha but not into bovine Gs alpha or human Gz alpha. Oxygen for methylene group substitutions in myristate result in analogs with comparable chain length and stereochemistry but marked reductions in hydrophobicity. Metabolic labeling studies with 6-, 11-, or 13 [3H]oxatetradecanoic acid indicated that they were incorporated into rat Gi alpha 1 and Go alpha with an efficiency that could be correlated with their accumulation into E. coli and their interactions with purified NMT in vitro. Octapeptides derived from the NH2-terminal sequences of these four G alpha polypeptides were tested as substrates for purified S. cerevisiae NMT. None were bound by the enzyme. Acidic residues at positions 7 and 8 appear to contribute to this effect; deletion of these two amino acids or addition of the next 9 residues of rat Go alpha produced active substrates. These results imply that productive interactions between NMT and G alpha protein substrates in vivo require structural features that are not fully represented within their NH2-terminal 8 residues. PMID- 1903792 TI - Characterization of a heparan sulfate and a peculiar chondroitin 4-sulfate proteoglycan from platelets. Inhibition of the aggregation process by platelet chondroitin sulfate proteoglycan. AB - A high molecular weight chondroitin sulfate proteoglycan (Mr 240,000) is released from platelet surface during aggregation induced by several pharmacological agents. Some details on the structure of this compound are reported. beta Elimination with alkali and borohydride produces chondroitin sulfate chains with a molecular weight of 40,000. The combined results indicate a proteoglycan molecule containing 5-6 chondroitin sulfate chains and a protein core rich in serine and glycine residues. Degradation with chondroitinase AC shows that a 4 sulfated disaccharide is the only disaccharide released from this chondroitin sulfate, characterizing it as a chondroitin 4-sulfate homopolymer. It is shown that this proteoglycan inhibits the aggregation of platelets induced by ADP. Analysis of the sulfated glycosaminoglycans not released during aggregation revealed the presence of a heparan sulfate in the platelets. Degradation by heparitinases I and II yielded the four disaccharide units of heparan sulfates: N,O-disulfated disaccharide, N-sulfated disaccharide, N-acetylated 6-sulfated disaccharide, and N-acetylated disaccharide. The possible role of the sulfated glycosaminoglycans on cell-cell interaction is discussed in view of the present findings. PMID- 1903793 TI - Regulation of poly(ADP-ribose) polymerase. Histone-specific adaptations of reaction products. AB - The post-translational poly ADP-ribosylation of proteins by the nuclear enzyme poly(ADP-ribose) polymerase (EC 2.4.2.30) involves a complex pattern of ADP ribose polymers. We have determined how this enzyme produces the various polymer size patterns responsible for altered protein function. The results show that histone H1 and core histones are potent regulators of both the numbers and sizes of ADP-ribose polymers. Each histone induced the polymerase to synthesize a specific polymer size pattern. Various other basic and/or DNA binding proteins as well as other known stimulators of poly(ADP-ribose) polymerase (spermine, MgCl2, nicked DNA) were ineffective as polymer size modulators. Testing specific proteolytic fragments of histone H1, the polymer number and polymer size modulating activity could be mapped to specific polypeptide domains. The results suggest that histones specifically regulate the polymer termination reaction of poly(ADP-ribose) polymerase. PMID- 1903794 TI - Structural/functional relationships between internal and external MSH receptors: modulation of expression in Cloudman melanoma cells by UVB radiation. AB - Expression of internal receptors for MSH is an important criterion for responsiveness to MSH by Cloudman melanoma cells (Orlow et al: J. Cell. Physiol., 142:129-136, 1990). Here, we show that internal and external receptors for MSH are of identical molecular weights (50-53 kDa) and share common antigenic determinants, indicating a structural relationship between the 2 populations of molecules. The internal receptors co-purified with a sub-cellular fraction highly enriched for small vesicles, many of which were coated. Ultraviolet B light (UVB) acted synergistically with MSH to increase tyrosinase activity and melanin content of cultured Cloudman melanoma cells, consistent with previous findings in the skin of mice and guinea pigs (Bolognia et al: J. Invest. Derm., 92:651-656, 1989). Preceding the rise in tyrosinase activity in cultured cells, UVB elicited a decrease in internal MSH binding sites and a concomitant increase in external sites. The time frame for the UVB effects on MSH receptors and melanogenesis, 48 hours, was similar to that for a response to solar radiation in humans. Together, the results indicate a key role for MSH receptors in the induction of melanogenesis by UVB and suggest a potential mechanism of action for UVB: redistribution of MSH receptors with a resultant increase in cellular responsiveness to MSH. PMID- 1903795 TI - Brefeldin A induces endoplasmic reticulum-associated O-glycosylation of galactosyltransferase. AB - Recent data from several laboratories show that Brefeldin A (BFA) induces a microtubule-dependent back-flow of Golgi components to the endoplasmic reticulum (ER) thereby causing disassembly of the Golgi apparatus and its fusion with ER membranes. In order to delineate the effect of BFA on resident Golgi proteins, we investigated its effect on biosynthesis, maturation and intracellular transport of galactosyltransferase (gal-T), an established trans-Golgi enzyme. Using a protocol of metabolic labeling/immunoprecipitation followed by electrophoretic/fluorographic analysis, we show that in the presence of BFA, gal T matures to a molecular form of 48.5 kD, a size intermediate between the 2 precursor forms of 44 and 47 and the mature form of 54 kD (Strous and Berger: J. Biol. Chem., 257:7623-28, 1982). Little mature form was detectable in the presence of BFA even after prolonged chase times of up to 28 hr. The intermediate form was sensitive to O-glycanase and endoglycosidase H, indicating early O glycosylation without sialylation and lack of complex N-glycosylation, respectively. In order to define the compartment responsible for O-glycosylation in the presence of BFA, a temperature block of 25 degrees C was applied which inhibited recovery of Golgi elements from BFA-induced fusion with ER. At this temperature and in absence of BFA, biosynthesis of gal-T was not appreciably affected, while maturation was completely inhibited as indicated by the presence of unmodified precursor forms of gal-T. After 60 min preincubation with BFA, a time period sufficient to demonstrate complete fusion of Golgi with ER, subsequent biosynthesis of gal-T at 25 degrees C in absence of BFA led to the intermediate form, while precursor forms were not detectable. These data provide direct evidence for BFA-induced redistribution to the EF of Golgi enzymes involved in O-glycosylation and their early functional involvement in biosynthesis of newly synthesized gal-T. PMID- 1903796 TI - Cellular mechanisms of ATP-induced hyperpolarization in renal epitheloid MDCK cells. AB - Previous studies have shown that ATP enhances intracellular calcium concentration and activates potassium channels in Madin Darby canine kidney (MDCK)-cells, thus leading to hyperpolarization of the cell membrane. The present study has been performed to elucidate the intracellular mechanisms involved. To this end, the effects of ATP on the potential difference across the cell membrane (PD), on formation of inositol phosphates, and on intracellular calcium concentration (Cai) have been analyzed in cells without or with pretreatment with pertussis toxin or 12-O-tetradecanoyl phorbol 13-acetate diester (TPA). In untreated cells, ATP leads to a sustained hyperpolarization and an increase of inositol 1,4,5 trisphosphate (IP3), inositol 1,3,4,5-tetrakisphosphate (IP4), and Cai. In the absence of extracellular calcium, the effect of ATP on PD and Cai is only transient. In cells pretreated with pertussis toxin, the effect of ATP on inositol trisphosphate is almost abolished, but ATP still leads to an increase of PD and Cai, which is sustained in the presence, and transient in the absence, of extracellular calcium. In cells pretreated with TPA, the effect of ATP on inositol trisphosphate is reduced and the effect on Cai blunted; but ATP still leads to a hyperpolarization of the cell membrane, which is sustained in the presence, and transient in the absence, of extracellular calcium. The observations indicate that ATP activates phospholipase C by a phorbol ester and pertussis toxin sensitive mechanism. In addition, ATP enhances Cai by pertussis toxin insensitive mechanisms allowing recruitment of calcium from both, extracellular fluid and intracellular stores. Calcium then activates the potassium channels and thus leads to the hyperpolarization of the cell membrane. PMID- 1903797 TI - Outcome prediction of acute renal failure in medical intensive care. AB - Data acquired prospectively from 134 patients with acute renal failure requiring dialysis in a medical intensive care unit (ICU) were analysed in order to derive indicators predicting ICU-survival. Mortality in the ICU was 56.7%. Linear discriminant analysis correctly predicted outcome in 79.9% at the start of dialysis, and 84.7% at 48 h after the first dialysis. The most important predictive variables were mechanical ventilation and low blood pressure. On the other hand, the total correct classification rates achieved by a standardised system for scoring ICU-patients (APACHE II) did not exceed 58.2%. It is concluded that outcome prediction by APACHE II and even by the discriminant functions is too inaccurate to become the basis for clinical decisions either concerning the initiation or the continuation of dialysis treatment in ARF. PMID- 1903798 TI - Colorimetric end-tidal carbon dioxide monitoring during transfer of intubated children. AB - We report the use of a cheap, pocket-sized colorimeter to assess the end-tidal carbon dioxide concentration during transfer of intubated children. The device provided breath by breath confirmation of tracheal tube placement and identified one episode of reduced pulmonary perfusion. We would advocate the use of this detector to provide early warning of tracheal tube displacement during the transfer of children weighing more than 15 kg. PMID- 1903799 TI - Inhibition of localized adhesion of enteropathogenic Escherichia coli to HEp-2 cells by immunoglobulin and oligosaccharide fractions of human colostrum and breast milk. AB - Secretory IgA (sIgA) purified from colostrum and breast milk obtained from 14 women inhibited the localized adherence of an enteropathogenic Escherichia coli (EPEC) to HEp-2 cells. Inhibition decreased as lactation continued even when the concentration of sIgA was maintained constant at 1 mg/ml. sIgA responded to a 94 kDa plasmid-encoded outer membrane protein implicated as the EPEC adherence factor. An oligosaccharide-enriched fraction (OEF) from these samples also inhibited the attachment of this EPEC. Inhibition by OEFs decreased as lactation continued because of a general reduction in oligosaccharide content. Localized adherence of six other EPEC was also inhibited by sIgA and OEF, whereas attachment of isolates with diffuse or aggregative adherence was not inhibited by these fractions. Experiments with purified oligosaccharide fractions revealed that EPEC attach to HEp-2 cells through a carbohydrate-mediated mechanism based on the preferential recognition of fucosylated residues in human milk. PMID- 1903800 TI - Synergistic bactericidal activity of rat serum with vancomycin against enterococci. AB - Animal models of infectious diseases may not predict clinical efficacy when species-related factors come into play. Recently, unexpected bactericidal activity of vancomycin alone against enterococci was observed in a rat model of endocarditis. A factor or factors in rat serum, but not rabbit or human serum, enhanced in vitro killing by vancomycin in four of five clinical isolates of enterococci. Bactericidal activity was maintained on dilution of rat serum to 5.0% and after exposure of serum to 56 degrees C for 30 min. Activity was lost by heating at 60 degrees C for 2 h, ultrafiltration, or absorption with bentonite or heat-killed bacteria. Rat serum appears to contain a factor or factors that contribute bactericidal activity to vancomycin, a drug normally bacteriostatic for these enterococci. The mechanism by which this factor enhances killing of enterococci by vancomycin is unknown. PMID- 1903801 TI - Resistance of Staphylococcus aureus recovered from infected foreign body in vivo to killing by antimicrobials. AB - Because persistence of infections associated with prosthetic material despite the use of appropriate antibiotics is a major clinical problem, the antimicrobial susceptibility of bacteria responsible for a chronic subcutaneous tissue cage infection in rat was investigated ex vivo. Three to 6 weeks after the initiation of infection, suspensions of two strains of Staphylococcus aureus recovered from the foreign body surface and surrounding fluid were exposed to either oxacillin, vancomycin, fleroxacin, gentamicin, or rifampin. The MBCs of these bacteria were markedly elevated, in most cases 128 to greater than 256 times higher than the MBC of batch culture S. aureus in either logarithmic or stationary phase. Kinetic studies showed the bacteria did not grow when incubated for 2 h in Mueller-Hinton broth, possibly reflecting dormancy. Their killing was slow and incomplete by all antibiotics at greater than 8 times their MIC. These data provide direct evidence of a decreased susceptibility of S. aureus to the killing effect of antimicrobials during chronic foreign body infections in vivo. PMID- 1903802 TI - Gentamicin-resistant, streptomycin-susceptible Enterococcus (Streptococcus) faecalis bacteremia. PMID- 1903803 TI - In vivo inhibition of granulopoiesis in acute inflammation requires T lymphocyte integrity. AB - In previous studies, we have shown that mice undergoing an inflammatory reaction induced by subcutaneous (s.c.) implantation of copper rods elaborate humoral factors that initially enhance, and subsequently inhibit, diffusion chamber (DC) granulopoiesis. In order to quantify the inhibition of DC granulopoiesis after inflammation, one to three copper rods were implanted s.c. either at the same place (1 abscess), or at different sites (multiple abscesses). There was an inverse relationship between the increase in the number of abscesses, and the number of DC granulocytic cells measured in the inhibitory phase. To investigate the role of T lymphocytes in the release of putative inhibitory factor(s) that act on DC cells, cyclosporin A (CyA), a T lymphocyte function inhibitor, was given orally each day (0.75 mg) to mice, starting two days before copper implantation. CyA abrogated the inflammation-related inhibition on DC spleen colony-forming units (CFU-s), granulocyte-macrophage colony-forming units (CFU gm), and total cell production. To confirm these results, DC were implanted in T cell deficient nude mice where no inhibition of DC cells was observed after inflammation. In conclusion, our data suggest that the in vivo inhibition of granulopoiesis is related to the level of the inflammatory stimulus and requires the functional integrity of T cells. PMID- 1903804 TI - Plasticity of presynaptic and postsynaptic elements of neuromuscular junctions repeatedly observed in living adult mice. AB - In order to assay the extent of ongoing synaptic remodelling in adult mouse neuromuscular junctions, dynamic structural changes of identified neuromuscular junctions were monitored in vivo over periods up to three months. Nerve terminal outgrowths as small as 1 micron were detectable with a new fluorescent tetanus toxin C-fragment stain combined with fluoresceinated alpha-bungarotoxin to stain postsynaptic acetylcholine receptors. With limited illumination, the new stain did not affect miniature endplate potential frequency, nor morphometric parameters of repeatedly observed neuromuscular junctions. At each observation, areas of presynaptic nerve terminal extending beyond underlying acetylcholine receptor ('preprojections'), and areas of acetylcholine receptor without overlying nerve terminal ('postprojections') were measured. Regions of the neuromuscular junction in which nerve terminal-postsynaptic acetylcholine receptor complexes either 'lengthened' or 'shortened' between observations were also measured. The total area of pre- and postprojections (relative to total junctional area) remained the same over three months but most had been replaced; only 20% of preprojections gave rise to lengthenings, the rest retracted or were unchanged. Lengthening and shortening of branches were about 1-2% of junctional area per month. These more permanent changes occurred against a background of ongoing transient nerve terminal outgrowth and retraction (which constituted 80% of all neuromuscular junction shape changes from one observation to the next, compared with 20% for the postsynaptic component). Breaks in the continuity of the underlying acetylcholine receptor were also observed between observations as were instances where acetylcholine receptor continuity was re-established. A newly observed form of plasticity was a shift in position and angle of pre existing branches. Establishment of new acetylcholine receptor-positive synaptic regions was mostly preceded by nerve terminal outgrowth on the previous observation. In animals in which spontaneous wheel-running increased locomotor activity approximately tenfold over a period of 35 days, the findings were identical to those in unexercised mice. In summary, in the adult neuromuscular junction, the nerve terminal, not the postsynaptic component, is the dynamic entity, continually changing shape on the scale of micrometers, with relatively small permanent changes. These ongoing exploratory excursions may supply the substrate for synaptic plasticity, which would involve regulation of the dynamics or stability of nerve outgrowth. PMID- 1903805 TI - Alveolar bone loss in two children with short-bowel syndrome receiving total parenteral nutrition. AB - Two preschool children who were receiving total parenteral nutrition (TPN) for short-bowel syndrome (SBS) were noted to have radiographic evidence of alveolar bone loss in their primary dentition. Tooth mobility, gingival recession, and premature tooth loss were clinical findings in these children. Both had a 2-year history of recurrent infections and fluctuating serum electrolytes prior to identification of their dental problems. PMID- 1903806 TI - Fibronectins in healing incision, excision and laser wounds. AB - The distribution of extracellular matrix (ECM) glycoproteins, fibronectins (FNs), was studied in healing scalpel incision, excision and laser wounds of rat tongue dorsal mucosa over a healing period of 42 days by indirect immunofluorescence microscopy using mono- and polyclonal antibodies. A monoclonal antibody (Mab) DH1 was used to detect extradomain-A containing cellular fibronectin (ED-AcFN), and a polyclonal antiserum was utilized to recognize all forms of FNs. In normal tissue ED-AcFN was confined only to the endothelia of larger blood vessels whereas in healing wounds abundant immunoreactive deposits were found in regenerating connective tissue and endothelia of capillaries. The increased content of FNs revealed with both antibodies subsided later on during healing. The results suggest that the locally produced ED-AcFN is essential for tissue regeneration and plays a distinct functional role during wound healing. Laser treatment did not affect the ability of wound fibroblasts to synthesize and deposit cFN. The results provide further evidence that certain embryonic characteristics are seen in regenerating tissue. PMID- 1903807 TI - Medication truths. PMID- 1903808 TI - Prevalence of mucosal lesions in the stomach and duodenum due to chronic use of NSAID in patients with rheumatoid arthritis or osteoarthritis, and interim report on prevention by misoprostol of diclofenac associated lesions. AB - We review preliminary findings of the screening and prophylaxis phases of a study of misoprostol in patients with arthritis receiving nonsteroidal antiinflammatory drugs (NSAID). Endoscopic evaluation of over 1,800 patients with rheumatoid arthritis or osteoarthritis, more than 95% of whom qualified for screening on the basis of continuous NSAID use over the prior 6 months, has revealed clinically significant gastroduodenal lesions in 37% and ulceration in 24%. In the prophylaxis phase, patients without significant lesions were randomized to receive misoprostol or placebo and NSAID therapy with diclofenac for 52 weeks. Product-limit and crude incidence analyses of data from patients thus far enrolled indicate that misoprostol is associated with significant protection against the development of gastroduodenal lesions compared with placebo after 12 or 24 weeks of study. No adverse effect of misoprostol administration on underlying arthritis activity has been observed thus far. Definitive conclusions await completion of the study. PMID- 1903809 TI - Prostaglandins and NSAID in the kidney. AB - In patients with underlying renal impairment, administration of nonsteroidal anti inflammatory drugs (NSAID) can produce a marked reduction of renal function via inhibition of renal prostaglandin (PG) synthesis. Recent findings indicate that administration of misoprostol can at least partially prevent NSAID induced nephrotoxic effects, suggesting a role for exogenous PG in this setting. These agents may also have important immunomodulatory effects. Other recently reported data show that use of misoprostol in renal transplant patients receiving immunosuppressive therapy with cyclosporine and prednisone was associated with a significant reduction in the incidence of acute graft rejection, as well as improved graft function irrespective of the occurrence of rejection. PMID- 1903810 TI - The role of prostaglandins in NSAID induced renal dysfunction. AB - Renal prostaglandins (PG) play an important role in regulating renal hemodynamics and excretory function in 2 conditions (1) which effective arterial blood volume is reduced and (2) chronic renal failure is reduced. The use of nonsteroidal antiinflammatory drugs (NSAID) in patients with these conditions can produce a significant decline in renal function, including decreased glomerular filtration rate and solute and water excretion, by inhibiting renal cyclooxygenase, and thus, PG production. Results of preliminary investigation with the PGE1 analog misoprostol suggest that exogenous PG analogs may be effective in counteracting the effects of NSAID in such settings. Further clinical studies will be needed to establish the role of PG in this setting. PMID- 1903811 TI - Are prostaglandins proinflammatory, antiinflammatory, both or neither? AB - Research on the role of prostaglandins (PG) in inflammation has been divided along 2 lines of inquiry. One supposes that PG are proinflammatory, explaining why nonsteroidal antiinflammatory drugs (NSAID), which prevent conversion of arachidonic acid to stable PG through cyclooxygenase inhibition, exert their antiinflammatory effects. The other supposes that PG are antiinflammatory, explaining the reductions in inflammation produced by these substances in various experimental models of arthritis. A number of proinflammatory actions of PG have been identified, including vasodilatation and hyperalgesia. However, these activities are relatively modest and do not appear to account for the antiinflammatory effects of NSAID; indeed, mechanisms for these effects that do not depend on cyclooxygenase inhibition have been advanced. A number of potential mechanisms for antiinflammatory effects of PGE have been identified, including inhibition of neutrophil activation, O2 release and leukotriene B4 and cytokine production. It is likely that the availability of orally active PGE analogs will permit study leading to an integrated understanding of PG activity and an answer to the question whether such agents will prove useful in the treatment of chronic inflammatory diseases. PMID- 1903812 TI - Cartilage maintenance in osteoarthritis: interaction of cytokines, NSAID and prostaglandins in articular cartilage damage and repair. AB - The structural integrity of the matrix of human articular cartilage is maintained by a dynamic equilibrium between synthesis and degradation. In osteoarthritis (OA), synthesis may be inhibited by the presence of subnanogram quantities of the cytokine interleukin 1 (IL-1), leading in the longterm to loss of matrix and susceptibility to mechanical damage. IL-1 may also inhibit the potential for repair processes to take place in this cartilage if continued synthesis and secretion of the cytokine occurs. Evidence is presented that animal and human cartilages are sensitive to the action of certain nonsteroidal antiinflammatory drugs (NSAID) in inhibiting the synthesis of cartilage proteoglycan and also diminishing the repair activity of cartilage recovering after IL-1. In OA cartilage, the sensitivity to action of NSAID may depend on the state of the tissue in terms of glycosaminoglycan (GAG) turnover and GAG synthetic activity of the indigenous chondrocytes. Preliminary investigations of the prostaglandin analog misoprostol on the synthetic repair activities of animal and human cartilage in the presence of NSAID are reported. PMID- 1903813 TI - Phenothrin lotion, the latest recruit in the battle against headlice: the results of two controlled comparative studies. AB - One hundred and one subjects with head louse infestation were entered into two separate studies, in which a phenothrin aqueous/alcoholic lotion was compared to a carbaryl lotion and a malathion lotion. Fifty subjects were treated with a single application of the phenothrin lotion, 28 with the carbaryl lotion and 23 with the malathion lotion. In the comparative study of the phenothrin and malathion lotions an inspection on the day following treatment showed no live lice remained, but that six of the subjects treated with malathion lotion still had evidence of viable eggs (p less than 0.05). In one subject viable eggs were still evident at two weeks post-treatment. There were no cases, however, of live lice or viable eggs at four weeks post-treatment. Mild cutaneous side-effects were reported in five subjects, the incidence of which was not significantly different by treatment group. One subject in the phenothrin and carbaryl lotion comparative study had evidence of live lice at one week post-treatment with phenothrin lotion. This subject received no further treatment and was clear of both live lice and viable eggs at subsequent visits. A separate case of live lice infestation was found at two weeks post-treatment in a subject treated with phenothrin lotion and at four weeks post-treatment in two subjects treated with carbaryl lotion. As these subjects were free of live lice infestation at previous follow-up visits it was highly probable that these were cases of re-infestation from another source.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1903814 TI - Reversal of unconsciousness by use of naloxone in a profoundly mentally handicapped epileptic. AB - The reversal of a state of impaired consciousness in a known epileptic following a period of prolonged post-ictal unconsciousness (with flexor response to nociceptive stimuli) was achieved by use of 0.4 mg naloxone intravenously. This decision was based on the similarity of the individuals clinical presentation to that seen in cases of opiate overdose. The implications of this dramatic clinical intervention are discussed. PMID- 1903815 TI - The potential of cryofixation and freeze substitution: observations and theoretical considerations. AB - The theoretical and experimental evidence in favour of cryofixation and freeze substitution are critically reviewed. The solubility of macromolecules in water is due to the hydration shells. Their behaviour at different temperatures and the consequences of their removal during the processing for embedding are explained. Gelation prior to the transfer into solvents prevents macromolecules aggregating. During substitution at low temperatures, DNA is gelled, justifying the use of the term cryofixation. It is proposed that the preservation of hydration shells at the lowest temperature, and their transformation into minute gaps after a rise of temperature, facilitates the exhibition of epitopes. PMID- 1903816 TI - Informational redundancy of tRNA(4Ser) and tRNA(7Ser) genes in Drosophila melanogaster and evidence for intergenic recombination. AB - Variant tRNA genes have been widely observed in multicellular eukaryotes. Recent biochemical studies have shown that some of them are expressed in a tissue- or a stage-specific manner. These findings would thus imply that certain modified tRNAs may be crucial for the development of the organism. Using Drosophila melanogaster as a model, we have taken a combined genetic and molecular approach to examine critically the possible biological functions of tRNA(4, 7Ser) genes. We showed that at least 50% of the total templates can be deleted from the genome without inducing abnormal phenotypes such as Minute, or a decrease in viability. In addition, two of the tRNASer variant genes that are unique in sequence are also completely dispensable. This strongly implies that even though they may be expressed in vivo, they play no essential role in the development of the fruitfly. By comparison with some of the corresponding tRNA genes in another sibling species, Drosophila erecta, our results suggest strongly that the variants are products non-reciprocal exchanges among the tRNA(4, 7Ser), genes. Such intergenic recombination events may have a major influence in the concerted evolution of the two gene families. PMID- 1903817 TI - Voltage dependence of bovine pulmonary artery endothelial cell function. AB - Vascular mediator synthesis in endothelial cells is Ca2+ sensitive. Bradykinin increases [Ca2+]i by releasing it from intracellular stores and by increasing influx across the plasmalemma. The latter is believed to occur through receptor operated channels. Although gating of these plasmalemmal channels is voltage insensitive, we hypothesized that Ca2+ influx would still be dependent on the Ca2+ electrochemical gradient and relative cation permeability. Using cultured bovine pulmonary endothelial cells we therefore measured: membrane voltage (Em) in single cells using the "tight seal" whole cell recording technique, Ca2+i in endothelial cell monolayers using fura-2, and arachidonic acid (AA) release using 3H-AA prior to and following exposure to bradykinin at different [K+]0. Our data indicate that the resting membrane potential of these cells is at least -67 mV in physiological saline and that the background resting membrane properties can be described with a (PNa/PK) ratio of approximately 0.027-0.040. Varying [K+]0 is shown to be an effective means for altering and controlling membrane potential and thus the calcium electrochemical gradient. Increases in [K+]0 lead to a concentration-dependent decrease in the magnitude of the Ca2+ transient and in the relative amount of arachidonic acid released following exposure to bradykinin suggesting that Ca2+ influx through the plasmalemma and AA release are regulated by the Ca2+ electrochemical gradient. In addition, a simple theoretical membrane conductance model is presented which is able to reconcile the wide range in apparent resting membrane potentials which have been reported for endothelial cells. PMID- 1903818 TI - The economic implications of high-risk abdominal aortic aneurysms. AB - Financial data of 102 patients undergoing elective and emergent abdominal aortic aneurysm repair over a 3-year period were evaluated in terms of postoperative length of stay, net revenue, total standard cost, and net margin. Cost reimbursement was based on diagnosis related group payments. Aneurysm repairs were classified as emergent, high-risk elective, or low-risk elective. A net loss of $409,459 was noted for the entire series. Emergent repairs, although only 12% of the population, accounted for 73% of total losses, with a mean loss of $24,655/patient. The mean net loss in the high-risk elective group was $3590/patient, and a net gain of $1132/patient was noted in the low-risk elective group. Length of stay outliers, defined as length of stay greater than 28 days, contributed to the bulk of the losses in the elective series and were predominant in the high-risk group. No preoperative comorbidity, other than high-risk classification, predicted outlier status. Length of stay correlated with total standard costs in all categories of aneurysm repair. Third party payment for length of stay outliers was inadequate; the diagnosis related group system warrants revision so that outlier reimbursement will be based on a tiered system derived from length of stay. PMID- 1903819 TI - The interaction of vasodilating drugs and sympathetic blockade in normal and ischemic canine hindlimbs. AB - The purpose of this study was to determine if intraarterial vasodilating drugs could augment the vasodilation produced by sympathetic blockade, such as occurs during epidural anesthesia. Papaverine (2 mg/min), nitroglycerin (1 microgram/kg/min), aand saline were infused into the femoral artery before and after lumbar sympathectomy in six arterially isolated canine hindlimbs. Femoral blood flow was controlled with a perfusion circuit at baseline (80 ml/min), half baseline (40 ml/min), and low (5 ml/min) flow rates so that hindlimb mean arterial pressure served as an index of peripheral vasodilation. At low flow, hindlimb arteriovenous oxygen content difference increased from 1.4 (baseline) to 6.2 ml O2/dl, consistent with peripheral ischemia. At baseline flow before sympathectomy, papaverine and nitroglycerin caused a decrease in hindlimb mean arterial pressure of 30% and 18%, respectively (p less than 0.01 vs saline control), equivalent to the decreases of 31% and 16% after sympathectomy (p less than 0.01). At half-baseline, papaverine and nitroglycerin reduced hindlimb mean arterial pressure by 22% and 12%, respectively (p less than 0.01), and caused comparable vasodilation after sympathectomy. Neither drug significantly changed hindlimb mean arterial pressure at low flow. Sympathectomy itself reduced hindlimb mean arterial pressure by 23% at baseline flow (p less than 0.01), by 18% at half-baseline flow (p less than 0.01), but had no effect at low flow. We conclude that intraarterial papaverine and nitroglycerin cause peripheral vasodilation that is synergistic with sympathectomy-induced adrenergic blockade, but they cannot augment vasodilation caused by peripheral ischemia. PMID- 1903820 TI - [Evaluation of nitroglycerin and prostaglandin E1 administration during cardiac surgery]. AB - Twenty patients, subjected to open heart surgery using standard moderate hypothermic and nonpulsatile extracorporeal circulation (ECC), were divided into two groups. In the control group only nitroglycerin was administered for the control of peripheral arterial blood pressure during ECC. In the PGE1 group, prostaglandin E1 (10 ng/kg/min) and nitroglycerin were used simultaneously. Plasma renin activity (PRA), angiotensin I (A I) and II (A II), aldosterone (Ald), epinephrine (E) and norepinephrine (NE) were increased to equal levels in both groups. PRA, A I, A II, and Ald increased five-fold from the initial value during ECC, while E and NE increased twenty-fold. Total peripheral vascular resistance was high in both groups, but the deviation from the normal level was significantly lower in the PGE1 group. Oxygen consumption during ECC revealed similar patterns of change in both groups. Peripheral arterial blood pressure was more easily controlled at acceptable levels in the PGE1 group. We concluded that the administration of both nitroglycerin and prostaglandin E1 may sustain satisfactory peripheral circulation during ECC. PMID- 1903821 TI - [Chylothorax developed after cardiac surgery in children: a report of three cases]. AB - Two children developed chylothorax after median sternotomy and a third child developed chylothorax after a Blalock-Taussig operation under the left thoracotomy. The first patient had a closure of ASD and a pulmonary valvotomy and then later developed chylothorax. The thoracic duct was ligated 10 cm just above the diaphragm at 28 days after the first operation because of unsuccessful conservative treatment. The second patient had a Blalock-Taussig operation and the third patient had radical operation for ECD and both developed chylothorax. The latter two patients were cured with conservative treatments such as the administration of Medium Chain Triglyceride or total parenteral nutrition with thoracic drainage. Children who developed chylothorax after cardiac surgery should be treated conservatively for at least the early postoperative period when circulatory and/or respiratory conditions are still unstable. PMID- 1903823 TI - Stimulation of endothelial secretion of tissue-type plasminogen activator by repetitive stretch. AB - Endothelial cells (EC) synthesize many of the fibrinolytic components and anticoagulants present in plasma. EC have been demonstrated to release tissue type plasminogen activator (t-PA) and its rapid inhibitor type 1 plasminogen activator inhibitor (PAI-1). In vivo, EC lining a blood vessel are exposed to the forces of the circulation, predominantly shear stress and pulsatile stretch. We have previously reported that repetitive stretch of EC in culture will stimulate prostacyclin secretion. In this study, the effects of cyclic stretch on the production of t-PA and PAI-1 by cultured EC were examined. EC harvested from human saphenous vein were seeded in culture plates with flexible membrane bottoms and grown to confluence. Vacuum (-20 kPa) was used to deform the membrane bottoms to 24% maximum strain. EC in the experimental group were subjected to 24% maximum strain at 60 cycles/min (0.5 sec elongation alternating with 0.5 sec relaxation), while control EC were grown on the same membranes but kept stationary in the same incubator. After 1, 3, and 5 days, the cell numbers were counted and the media were collected and analyzed for t-PA and PAI-1 by ELISA. The result shows a significant increase in t-PA production with the cyclic stretch on Days 3 and 5. There was no significant difference in PAI-1 levels in stretched versus stationary EC. We concluded that cyclic stretch of EC in vitro can selectively stimulate t-PA production and may account for the relative nonthrombogenicity of the endothelium in vivo. PMID- 1903822 TI - A phase II combination trial with recombinant human tumor necrosis factor and gamma interferon in patients with colorectal cancer. AB - Recombinant human tumor necrosis factor (TNF) is a cytotoxic monokine with immunomodulatory functions. Gamma interferon (g-IFN) synergizes with TNF in many ways. We therefore conducted a Phase I/II combination trial with TNF and g-IFN at an immunomodulatory dose level in 16 patients with colorectal cancer. TNF (50 micrograms/m2 in a 30 min infusion) and g-IFN (100 micrograms in subcutaneous injections) were administered daily Monday through Friday for 4 weeks. Two cases of major toxicity, one acute renal failure and one case of severe thrombocytopenia, led to discontinuation of study medication in these patients. Toxicities in remaining patients were manageable with conservative treatment. Changes in laboratory values included leukopenia, anemia and thrombocytopenia. Alterations in lipid metabolism and changes in serum levels of acute phase proteins were observed. Increase in both total lymphocytes and a Leu 11 positive subpopulation, as well as an induction of measurable interleukin 2 serum levels in a subgroup of patients, were noted. Response results of 14 evaluable patients were one patient with a mixed response, 4 with stable disease and 9 with disease progression. Median survival was 23.5 weeks with only one patient alive after 71 weeks. Therefore the drug combination of TNF/g-IFN in the chosen regimen cannot be recommended for the treatment of patients with colorectal cancer. PMID- 1903824 TI - Kupffer cell tumor necrosis factor-alpha production is suppressed during liver regeneration. AB - Mammalian liver regeneration following resection invokes intrinsic hepatic responses which result in rapid tissue repair. The role of soluble immune cytokines in this phenomenon is not known. The capacity of Kupffer cells (KC) from regenerating liver to produce the potent cytokine TNF-alpha was evaluated. Twenty-four hours after 70% partial hepatectomy (PHx) or sham operation, Kupffer cells were harvested from collagenase-digested Wistar-Furth rat livers and purified (greater than 95% by phagocytosis) by adherence. Following overnight culture with or without the cyclooxygenase inhibitor indomethacin (10 microM), 5 x 10(5) KC were repleted with fresh media with or without 2.5 micrograms/ml lipopolysaccharide (LPS). Supernatant TNF-alpha activities (units/ml) were measured using the L929 fibroblast lysis assay. With LPS, sham KC TNF-alpha levels were significantly higher (P less than 0.001) than those for PHx KC. Indomethacin significantly increased PHx KC TNF-alpha levels, but did not affect those for sham KC, suggesting autoregulation by arachidonic acid cyclooxygenase metabolites following PHx. We conclude that KC TNF-alpha production is suppressed following PHx by a mechanism apparently regulated by eicosanoid metabolism. During the stress of hepatic regeneration, a coordinated limitation of excessive TNF-alpha responses by PHx liver KC may naturally protect the host. PMID- 1903825 TI - Influence of intraalveolar oxygen concentration on lung preservation in a rabbit model. AB - We previously reported the use of an inexpensive screening model for lung preservation involving ventilation and perfusion of excised rabbit lungs after their preservation. We now have extended this model by perfusing the preserved lung in cross circulation with an anesthetized rabbit to permit stable reperfusion of the preserved lungs for 60 minutes. With this model we compared the results of lung preservation with the lungs inflated with nitrogen, room air, or 100% oxygen during 24 hours of hypothermic storage. Four groups of animals were studied: group 1, excision and immediate evaluation; group 2, inflation with room air and storage for 24 hours at 10 degrees C; group 3, same as group 2, with 100% oxygen for inflation during storage; group 4, same as group 2, with 100% nitrogen for inflation during storage. Assessment of the ex vivo perfused lung consisted of (1) blood gas analysis of inflow and outflow blood at 10-minute intervals; (2) continuous pulmonary artery and airway pressure monitoring; (3) measurement of pulmonary venous oxygen tension after 1 hour of reperfusion, with inflow oxygen tension adjusted to 15 mm Hg; (4) wet/dry weight ratio. We conclude that the paracorporeal circuit does not, in itself, cause lung injury over a 1 hour period; lungs preserved with nitrogen inflation rapidly became edematous and failed to function on reperfusion. Preservation with 100% oxygen inflation appears superior to inflation with room air. PMID- 1903826 TI - End-tidal carbon dioxide tension as a monitor of native blood flow during resuscitation by extracorporeal circulation. AB - In a porcine model of cardiac arrest, we investigated end-tidal carbon dioxide tension as a monitor of native blood flow during resuscitation by extracorporeal circulation. After 15 minutes of cardiac arrest and after precordial compression and transthoracic countershocks had failed, extracorporeal circulation consistently restored spontaneous circulation. Native end-tidal carbon dioxide tension, which averaged 29.8 +/- 1.0 mm Hg before arrest, was only 5.2 +/- 0.8 mm Hg during precordial compression. After the start of extracorporeal circulation, native end-tidal carbon dioxide tension was measured during 15-second interruptions of pump flow. End-tidal carbon dioxide tension progressively increased with a corresponding increase in native cardiac index. The correlation coefficients between end-tidal carbon dioxide tension and native cardiac index averaged 0.92 +/- 0.03 (mean +/- standard error of the mean). When end-tidal carbon dioxide tension exceeded 15 mm Hg, mean aortic pressure in each instance was 60 mm Hg or greater, and the animal was successfully weaned from extracorporeal support. We conclude that end-tidal carbon dioxide tension serves as a reliable monitor of blood flow through the lung and therefore of native cardiac output during weaning from extracorporeal circulation. It therefore indicates when native cardiac output is likely to be adequate to sustain spontaneous circulation. PMID- 1903827 TI - Heterogeneous effects of exogenous lymphokines on lymphoproliferation of elderly subjects. AB - Although the ability of peripheral blood mononuclear cells of a population of elderly subjects (mean age 85.3) to proliferate in response to the T cell mitogens phytohemagglutinin (PHA) and concanavalin A (Con A) is significantly reduced compared to young subjects (mean age 24.7), the response of the elderly subjects is heterogeneous. While 47% of the elderly subjects responded at about half the level of young controls, 15% responded at less than 20% the level and the remaining 38% responded comparably to young controls. Similar heterogeneity was observed in lymphokine production. However, there was no significant correlation between the level of proliferative response and production of either interleukin 2 (IL-2) or interferon gamma (IFN-g). In an effort to further explore the role of lymphokines in the decreased proliferative response of elderly subjects, various concentrations of exogenous IL-2 and/or IFN-gamma were added at the initiation of the mitogen stimulated cultures. Similar increases in both the level of response and the number of subjects demonstrating an increase was observed for both young and elderly subjects upon addition of either IL-2 or IFN gamma. However, addition of a combination of IL-2 and IFN produced more pronounced effects in the elderly subjects. Approximately 1/3 of the elderly subjects who demonstrated decreased PHA-induced proliferation doubled their PHA induced proliferative response upon addition of a combination of lymphokines. The amounts of IL-2 and IFN-gamma required for this increase varied for each individual.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1903828 TI - [Hepatitis virus B, C and delta infection in carriers of the human immunodeficiency virus]. AB - BACKGROUND: Human immunodeficiency virus (HIV) shares transmission mechanisms with some hepatotropic viruses, such as hepatitis B (HBV), C (HCV) and delta (HDV) viruses. METHODS: To evaluate the prevalence of infection in a group of 100 male prisoners, carriers of the human immunodeficiency virus, the serologic markers of these viruses were investigated with radioimmunoassay and enzyme immunoassay. RESULTS: In 96 and 65% of individuals, respectively, some marker of HBV and HCV were found. The association anti-HBs and anti-HBc was present in 51 cases; 36 of them (71%) were carriers of anti-HCV. HBsAg was found in 7 individuals, 5 of which had antibodies against HDV. The pattern anti-HBs, anti HBc, anti-HCV, HIV anti-env and anti-core was found in 34 individuals. CONCLUSIONS: These data show the high prevalence of HBV and HCV in the study population, indicating the need to systematically investigate markers of these viruses to establish measures for prevention and control. PMID- 1903829 TI - Induction of chromosome aberrations and sister chromatid exchange by indirectly acting mutagens in immortal mouse and rat hepatocyte lines. AB - Two immortalized, differentiated mouse (FMH-202) and rat (NRL-Cl-A) hepatocyte lines were examined for their capacity to activate the indirectly acting mutagens aflatoxin B1 (AFB1), cyclophosphamide (CP), benzo[a]pyrene (BaP) and 7,12 dimethylbenz[a]anthracene (DMBA) into DNA reactive metabolites as determined by the induction of structural chromosome aberrations (CA) and sister chromatid exchange (SCE). The rat and mouse hepatocyte lines were able to efficiently activate either AFB1, BaP and DMBA, or BaP and DMBA, respectively, as shown by significant clastogenic responses. SCE induction was apparent in both cell lines in response to each of the compounds. Due to the observed long-term maintenance of various liver specific functions (at least 3-4 years) as well as the capability to metabolize xenobiotics (at least 30 passages) these cells may be a suitable assay system for the detection of indirectly acting mutagens. PMID- 1903830 TI - Metabolic formation, synthesis and genotoxicity of the N-hydroxy derivative of the food mutagen 2-amino-1-methyl-6-phenylimidazo (4,5-b) pyridine (PhIP). AB - Hepatic microsomes from rats pretreated with PCB were found to metabolize the food mutagen 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP) to two major metabolites, one of which was identified as the N-hydroxy derivative, 2-hydroxy amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (N-OH-PhIP). This identification was based on mass spectral (MS), UV and HPLC data by comparison with N-OH-PhIP prepared by chemical synthesis, as well as the specific activity of the compound in the Ames Salmonella test. Synthetic N-OH-PhIP was prepared by catalytic reduction of the nitro derivative of PhIP, which was synthesized from PhIP by diazotization and reaction with sodium nitrite. N-OH-PhIP was mutagenic to Salmonella typhimurium TA98 without metabolic activation and had a specific mutagenic activity of 2700 revertants/nmol. N-OH-PhIP thus seems to be a proximate mutagenic metabolite of PhIP. Other direct acting mutagens were not detected in the microsomal incubation mixture after HPLC separation. N-OH-PhIP also induced sister chromatid exchange (SCE) in Chinese hamster ovary cells (CHO cells) without metabolic activation. The specific activity of N-OH-PhIP in this assay was approximately 3 times higher than the activity of PhIP with microsomal activation. PMID- 1903831 TI - [The effect of immunological response on wound healing in rat with liver cirrhosis]. AB - We examined the reaction of cell-mediated immunity with wound healing in liver cirrhosis. Cirrhosis was induced in male Wistar rats with a basal diet supplemented with 0.06% dimethylaminoazobenzene (DAB) over a four week period. Rats fed with a basal diet were served as control. Midline laparotomy of 2cm was performed. We determined the number of lymphocyte, the collagen content and the bursting pressure of the abdominal wound. In addition, the delayed hypersensitivity response was measured using dinitrofluorobenzene (DNFB) applied to the ears. The rats with cirrhosis showed significant decrease in the number of lymphocytes, the collagen content and the bursting pressure of the wound in comparison with the control rats. Also the rats with cirrhosis had depressed DNFB response. The response of infiltrating lymphocytes in the ear was similar to the response of lymphocytes in the wound. There was a positive correlation between the lymphocyte number and the collagen content in the wound. Moreover, the bursting pressure had a significant correlation with the number of lymphocyte in the wound. The data strongly suggest that depressed cell-mediated immunity impairs wound healing in liver cirrhosis. PMID- 1903832 TI - [Targeting cancer chemotherapy for metastatic liver cancer--effects of DSM on hepatic hemodynamics and on clinical outcome]. AB - The effects of intra-arterial infusion of degradable starch microsphere (DSM) on hepatic hemodynamics were studied in 22 patients with metastatic liver cancer and the clinical outcome with mitomycin C (MMC) combined with DSM was reported herein. Hepatic arterial blood flow, measured with a transit-time ultrasonic blood flow meter, changed 283 +/- 27 ml/min to 40 +/- 36 ml/min by an hepatic arterial infusion of DSM and, a mean occlusion time aS 24 +/- 11 min. Combined infusion with DSM and MMC reduced MMC levels in the peripheral blood at 0.0248 less than p less than 0.0421, compared with those by an infusion with MMC alone and consequently, these findings proved to result from intrahepatic accumulation of MMC. RI-angiography using 99mTc-macroaggregated albumin (99mTc-MAA) was performed to examine hemodynamic changes in the metastatic liver and, a tumor (T) to non-tumor (N) ratio of 99mTc-MAA accumulation increased 0.37 to 0.62 by combined use of DSM. Thus, an intra-arterial infusion combined DSM and MCC was performed for 22 patients with unresectable hepatic metastases. Tumor regression was observed in 16 patients (73%). Side effects possibly attributable to DSM was transient nausea and vomiting. These results show that combined use of DSM is effective for intra-arterial chemotherapy against metastatic hepatic cancer. PMID- 1903833 TI - [Growth of the aortic anastomosis in puppies--comparison of monofilament suture materials, whether absorbable or nonabsorbable, and of suture techniques, whether continuous or interrupted]. AB - This study compared the growth of vascular anastomoses performed with either polypropylene or polydioxanone sutures and with either continuous running suture or interrupted suture technique. Primary end-to-end anastomoses of the infrarenal aorta were performed in 38 puppies. Nineteen were performed with 5-0 polypropylene sutures; in ten all sutures were placed in continuous fashion, and in nine in interrupted fashion. The other nineteen were performed with 5-0 polydioxanone sutures; in ten the sutures were placed in continuous fashion, and in nine in interrupted fashion. The animals were subjected to the repeated aortograms at 2, 4, 8 weeks, 6 months and 1 year following operation. Each abdominal aorta was subjected to burst test, and pathological examination. All anastomoses were patent and tolerated burst-test (300 mmHg). Neither aneurysm nor dilatation of anastomotic site was observed. Anastomotic area was significantly smaller and more stenotic in the continuous polypropylene suture group than in other three groups at 8 weeks, 6 months and 1 year following operation. There was no significant difference among these three groups. No suture materials were observed in the polydioxanone suture groups after 6 months following operation. This study suggests that polydioxanone suture will be useful for the repair of cardiovascular anomalies where growth of the suture line is required. PMID- 1903834 TI - Systematic characterization of curved DNA segments randomly cloned from Escherichia coli and their functional significance. AB - In addition to the set of curved DNA segments isolated previously from Escherichia coli, another set of curved DNA segments has now been isolated. To gain an insight into the functional significance of these curved DNA sequences, systematic analyses were carried out, which included not only mapping of the precise locations of the segments on the E. coli chromosome but also clarification of the gene organization in the chromosomal regions surrounding the curved DNA sequences. It was demonstrated that most of the curved DNA sequences, which have been characterized so far, appear to be located immediately upstream of the coding sequences of adjacent genes. It was also demonstrated that an E. coli histone-like protein, named H-NS (or H1a), exhibits a strong affinity for naturally occurring curved DNA sequences in regions upstream promoters. PMID- 1903835 TI - Response to heat shock of gene 1, a Drosophila melanogaster small heat shock gene, is developmentally regulated. AB - The expression of gene 1, a member of the small heat shock gene family from the Drosophila melanogaster chromosomal locus 67B was studied. In contrast to the other heat shock genes, the response of gene 1 to stress was modulated during development. In the absence of stress, gene 1 was expressed at the beginning of pupation, and at a very low level in adult males. Expression of gene 1 was substantially increased by heat shock in pupae, but was one to two orders of magnitude lower in adults or in embryos. Under the same conditions, hsp70 or hsp26 were induced to similar levels in all stages. This developmental effect could be mimicked in cultured Drosophila cells: expression of gene 1 was stimulated by heat shock in the presence, but not in the absence, of the moulting hormone ecdysterone, while the level of expression of hsp26 and hsp70 in response to heat shock was independent of the presence of the hormone. Thus, the presence and activity of the heat shock transcription factor are not sufficient for the maximal response of gene 1 to stress. These results suggest that the heat shock activator protein requires additional factors, which are developmentally regulated, to activate transcription of gene 1. Furthermore, S1 nuclease mapping analysis revealed several gene 1 mRNA species, which are generated by the use of alternative polyadenylation sites and by the use of differentially regulated transcriptional initiation sites. PMID- 1903836 TI - In vivo stimulation of a chimeric promoter by binding sites for nuclear factor I. AB - Nuclear factor I (NFI) is composed of a family of site-specific DNA-binding proteins which recognize a DNA-binding site with the consensus sequence TGGC/A(N)5GCCAA. Binding sites for NFI have previously been shown to stimulate mRNA synthesis in vitro when present upstream of the TATA box of the adenovirus major late promoter (AdMLP). We have examined the effect of NFI-binding sites on transcription in vivo in transiently transfected HeLa and COS cells. An NFI binding site isolated from the human genome activated expression from the minimal AdMLP in vivo in both the absence and presence of the simian virus 40 enhancer. A point mutation that decreased NFI binding affinity for the site in vitro reduced expression to near the basal level of the AdMLP. Several NFI-binding sites which differed in their spacer and flanking sequences were tested for their ability to activate expression in vivo. The ability of these sites to activate expression correlated with the strength of NFI binding in vitro. An NFI-binding site stimulated expression equally well when placed from 33 to 65 bp upstream of the TATA box. However, expression dropped to basal levels when the site was located from 71 to 77 bp upstream of the TATA box. These studies indicate that an NFI binding site in this chimeric promoter activates expression in vivo only if located within a critical distance of the TATA box. PMID- 1903837 TI - Pheromone response elements are necessary and sufficient for basal and pheromone induced transcription of the FUS1 gene of Saccharomyces cerevisiae. AB - The FUS1 gene of Saccharomyces cerevisiae is transcribed in a and alpha cells, not in a/alpha diploids, and its transcription increases dramatically when haploid cells are exposed to the appropriate mating pheromone. In addition, FUS1 transcription is absolutely dependent on STE4, STE5, STE7, STE11, and STE12, genes thought to encode components of the pheromone response pathway. We now have determined that the pheromone response element (PRE), which occurs in four copies within the FUS1 upstream region, functions as the FUS1 upstream activation sequence (UAS) and is responsible for all known aspects of FUS1 regulation. In particular, deletion of 55 bp that includes the PREs abolished all transcription, and a 139-bp fragment that includes the PREs conferred FUS1-like expression to a CYC1-lacZ reporter gene. Moreover, three or four copies of a synthetic PRE closely mimicked the activity conferred by the 139-bp fragment, and even a single copy of PRE conferred a trace of activity that was haploid specific and pheromone inducible. In the FUS1 promoter context, four copies of the synthetic PRE inserted at the site of the 55-bp deletion restored full FUS1 transcription. Sequences upstream and downstream from the PRE cluster were important for maximal PRE-directed expression but, by themselves, did not have UAS activity. Other yeast genes with PREs, e.g., STE2 and BAR1, are more modestly inducible and have additional UAS elements contributing to the overall activity. In the FUS1 promoter, the PREs apparently act alone to confer activity that is highly stimulated by pheromone. PMID- 1903838 TI - cis-acting sequences required for expression of the divergently transcribed Drosophila melanogaster Sgs-7 and Sgs-8 glue protein genes. AB - The Sgs-7 and Sgs-8 glue genes at 68C are divergently transcribed and are separated by 475 bp. Fusion genes with Adh or lacZ coding sequences were constructed, and the expression of these genes, with different amounts of upstream sequences present, was tested by a transient expression procedure and by germ line transformation. A cis-acting element for both genes is located asymmetrically in the intergenic region between -211 and -43 bp relative to Sgs 7. It is required for correct expression of both genes. This element can confer the stage- and tissue-specific expression pattern of glue genes on a heterologous promoter. An 86-bp portion of the element, from -133 to -48 bp relative to Sgs-7, is shown to be capable of enhancing the expression of a truncated and therefore weakly expressed Sgs-3 fusion gene. Recently described common sequence motifs of glue gene regulatory elements (T. Todo, M. Roark, K. Vijay Raghavan, C. A. Mayeda, and E.M. Meyerowitz, Mol. Cell. Biol. 10:5991-6002, 1990) are located within this 86-bp region. PMID- 1903839 TI - The yeast SLY gene products, suppressors of defects in the essential GTP-binding Ypt1 protein, may act in endoplasmic reticulum-to-Golgi transport. AB - It has been shown previously that defects in the essential GTP-binding protein, Ypt1p, lead to a block in protein transport from the endoplasmic reticulum (ER) to the Golgi apparatus in the yeast Saccharomyces cerevisiae. Here we report that four newly discovered suppressors of YPT1 deletion (SLY1-20, SLY2, SLY12, and SLY41) to a varying degree restore ER-to-Golgi transport defects in cells lacking Ypt1p. These suppressors also partially complement the sec21-1 and sec22-3 mutants which lead to a defect early in the secretory pathway. Sly1p-depleted cells, as well as a conditional lethal sly2 null mutant at nonpermissive temperatures, accumulate ER membranes and core-glycosylated invertase and carboxypeptidase Y. The sly2 null mutant under restrictive conditions (37 degrees C) can be rescued by the multicopy suppressor SLY12 and the single-copy suppressor SLY1-20, indicating that these three SLY genes functionally interact. Sly2p is shown to be an integral membrane protein. PMID- 1903840 TI - Organizational analysis of elav gene and functional analysis of ELAV protein of Drosophila melanogaster and Drosophila virilis. AB - Drosophila virilis genomic DNA corresponding to the D. melanogaster embryonic lethal abnormal visual system (elav) locus was cloned. DNA sequence analysis of a 3.8-kb genomic piece allowed identification of (i) an open reading frame (ORF) with striking homology to the previously identified D. melanogaster ORF and (ii) conserved sequence elements of possible regulatory relevance within and flanking the second intron. Conceptual translation of the D. virilis ORF predicts a 519 amino-acid-long ribonucleoprotein consensus sequence-type protein. Similar to D. melanogaster ELAV protein, it contains three tandem RNA-binding domains and an alanine/glutamine-rich amino-terminal region. The sequence throughout the RNA binding domains, comprising the carboxy-terminal 346 amino acids, shows an extraordinary 100% identity at the amino acid level, indicating a strong structural constraint for this functional domain. The amino-terminal region is 36 amino acids longer in D. virilis, and the conservation is 66%. In in vivo functional tests, the D. virilis ORF was indistinguishable from the D. melanogaster ORF. Furthermore, a D. melanogaster ORF encoding an ELAV protein with a 40-amino-acid deletion within the alanine/glutamine-rich region was also able to supply elav function in vivo. Thus, the divergence of the amino-terminal region of the ELAV protein reflects lowered functional constraint rather than species-specific functional specification. PMID- 1903843 TI - [Antibiotic inhalation in cystic fibrosis. A review of the literature]. AB - Although antibiotic aerosols are widely used for the long-term treatment of chronic Pseudomonas aeruginosa infection in patients with cystic fibrosis, there are no clear therapeutic guidelines for the use of inhaled antibiotics due to the lack of large, well-controlled studies. This paper will review the current knowledge on the deposition and pharmacokinetics, the indication, clinical benefit and possible adverse reactions of inhaled antibiotics. PMID- 1903842 TI - A 32-kilodalton protein binds to AU-rich domains in the 3' untranslated regions of rapidly degraded mRNAs. AB - An AU-rich sequence present within the 3' untranslated region has been shown to mark some short-lived mRNAs for rapid degradation. We demonstrate by label transfer and gel shift experiments that a 32-kDa polypeptide, present in nuclear extracts, specifically interacts with the AU-rich domains present within the 3' untranslated region of human granulocyte-macrophage colony-stimulating factor, c fos, and c-myc mRNAs and a similar domain downstream of the poly(A) addition site of the adenovirus IVa2 mRNA. Competition experiments and partial protease analysis indicated that the same polypeptide interacts with all four RNAs. A single AUUUA sequence in a U-rich context was sufficient to signal binding of the 32-kDa polypeptide. Insertion of three copies of this minimal recognition site led to markedly reduced accumulation of beta-globin RNA, while the same insert carrying a series of U-to-G changes had little effect on RNA levels. Steady-state levels of beta-globin-specific nuclear RNA, including incompletely processed RNA, and cytoplasmic mRNA were reduced. Cytoplasmic mRNA containing the AU-rich recognition sites for the 32-kDa polypeptide exhibited a half-life shorter than that of mRNA with a mutated insert. We suggest that binding of the 32-kDa polypeptide may be involved in the regulation of mRNA half-life. PMID- 1903841 TI - Translation initiation factor 5A and its hypusine modification are essential for cell viability in the yeast Saccharomyces cerevisiae. AB - Translation intitiation factor eIF-5A (previously named eIF-4D) is a highly conserved protein that promotes formation of the first peptide bond. One of its lysine residues is modified by spermidine to form hypusine, a posttranslational modification unique to eIF-5A. To elucidate the function of eIF-5A and determine the role of its hypusine modification, the cDNA encoding human eIF-5A was used as a probe to identify and clone the corresponding genes from the yeast Saccharomyces cerevisiae. Two genes named TIF51A and TIF51B were cloned and sequenced. The two yeast proteins are closely related, sharing 90% sequence identity, and each is ca. 63% identical to the human protein. The purified protein expressed from the TIF51A gene substitutes for HeLa eIF-5A in the mammalian methionyl-puromycin synthesis assay. Strains lacking the A form of eIF 5A, constructed by disruption of TIF51A with LEU2, grow slowly, whereas strains lacking the B form, in which HIS3 was used to disrupt TIF51B, show no growth rate phenotype. However, strains with both TIF51A and TIF51B disrupted are not viable, indicating that eIF-5a is essential for cell growth in yeast cells. Northern (RNA) blot analysis shows two mRNA species, a larger mRNA (0.9 kb) transcribed from TIF51A and a smaller mRNA (0.8 kb) encoded by TIF51B. Under the aerobic growth conditions of this study, the 0.8-kb TIF51B transcript is not detected in the wild-type strain and is expressed only when TIF51A is disrupted. The TIF51A gene was altered by site-directed mutagenesis at the site of hypusination by changing the Lys codon to that for Arg, thereby producing a stable protein that retains the positive charge but is not modified to the hypusine derivative. The plasmid shuffle technique was used to replace the wild-type gene with the mutant form, resulting in failure of the yeast cells to grow. This result indicates that hypusine very likely is required for the vital in vivo function of eIF-5A and suggests a precise, essential role for the polyamine spermidine in cell metabolism. PMID- 1903844 TI - Purification and characterization of DNA polymerases from Plasmodium berghei. AB - DNA polymerases from the malaria parasite Plasmodium berghei were purified more than 50-fold. Several distinct enzymatic activities were isolated that could be distinguished by the use of various specific DNA polymerase inhibitors. In particular, subdivision into an aphidicolin-sensitive and an aphidicolin resistant group was possible. Further analysis allowed a better comparison with host DNA polymerases and indicated that one aphidicolin-sensitive DNA polymerase resembled DNA polymerase alpha displaying processive DNA synthesis and using RNA primers, whereas another aphidicolin-sensitive DNA polymerase was distributive and only used DNA primers. Marked differences from the host enzymes do exist, however, such as insensitivity to BuPdGTP. Another P. berghei DNA polymerase was isolated that showed characteristics of a DNA polymerase beta-like enzyme, but which differed from host DNA polymerase beta in its insensitivity to dideoxynucleotides. PMID- 1903845 TI - A carbon-13 nuclear magnetic resonance analysis of the products of glucose metabolism in Leishmania pifanoi amastigotes and promastigotes. AB - The major products of glucose metabolism were determined for amastigotes and promastigotes of Leishmania (mexicana) pifanoi under aerobic and anaerobic conditions using carbon-13 nuclear magnetic resonance. Under aerobic conditions, the major products for both forms were carbon dioxide, succinate, malate, acetate and alanine. Succinate was the dominant metabolite of promastigotes, whereas acetate and alanine were most abundant with amastigotes. Under anaerobic conditions, promastigotes produced glycerol as the dominant metabolite, along with lesser amounts of succinate, acetate and alanine; acetate and alanine remained major metabolites in amastigotes, with an increase in the relative amount of succinate and the production of some glycerol. Promastigotes generated carbon dioxide at a 5-fold greater rate than amastigotes under aerobic conditions, but this rate was reduced by more than 95% in the absence of oxygen. Amastigotes were relatively less affected by lack of oxygen and produced carbon dioxide at a rate comparable to promastigotes under anaerobic conditions. The presence of carbohydrates with a possible role in storage was detected in both promastigotes and amastigotes. PMID- 1903846 TI - The efficacy in Navajo infants of a conjugate vaccine consisting of Haemophilus influenzae type b polysaccharide and Neisseria meningitidis outer-membrane protein complex. AB - BACKGROUND AND METHODS: Several conjugate vaccines against Haemophilus influenzae type b have been developed in the search for one that induces protection even in young infants. We evaluated the safety and efficacy of a conjugate vaccine that links the H. influenzae type b capsular polysaccharide to the outer-membrane protein complex (OMPC) of Neisseria meningitidis serogroup B. We conducted a double-blind, placebo, controlled trial in Navajo infants, who are at high risk for systemic infections caused by H. influenzae type b. The infants were randomly assigned to receive the first dose of vaccine or placebo at 42 to 90 days of age and the second at 70 to 146 days of age. RESULTS: Of the infants in the trial, 2588 were assigned to receive the vaccine and 2602 to receive placebo. The mean follow-up was 269 days in the vaccine group and 267 days in the placebo group. Before the age of 18 months, there was 1 systemic H. influenzae type b infection in the vaccine group, as compared with 22 in the placebo group (P less than 0.001; point estimate of efficacy, 95 percent; 95 percent confidence interval, 72 to 99 percent). Of the 22 H. influenzae type b infections in the placebo group, 13 were meningitis. Among the children who received both doses, there was 1 H. influenzae type b infection in the vaccine group (n = 2056) and 14 in the placebo group (n = 2105) (P less than 0.001; point estimate of efficacy, 93 percent; 95 percent confidence interval, 53 to 98 percent). The single infection in the vaccine group occurred at 15 1/2 months of age in an infant with osteomyelitis. Between the first and second doses there were no H. influenzae type b infections in the vaccine group and eight in the placebo group (P less than 0.005; point estimate of efficacy, 100 percent; 95 percent confidence interval, 41 to 100 percent). CONCLUSIONS: The H. influenzae type b OMPC vaccine, administered at 2 and 4 months of age, is safe and induces a high rate of protection against invasive disease caused by H. influenzae type b in infants under the age of 18 months. Protection begins after the first dose. PMID- 1903848 TI - Monozygotic twins with centrotemporal EEG spikes--differences in clinical expression and effects of valproate therapy. PMID- 1903847 TI - Recombinant granulocyte-macrophage colony-stimulating factor after autologous bone marrow transplantation for lymphoid cancer. AB - BACKGROUND: The period of neutropenia after autologous bone marrow transplantation results in substantial morbidity and mortality. The results of previous phase I-II clinical trials suggest that recombinant human granulocyte macrophage colony-stimulating factor (rhGM-CSF) may accelerate neutrophil recovery and thereby reduce complications in patients after autologous bone marrow transplantation. METHODS: We conducted a randomized, double-blind, placebo controlled trial at three institutions. The study design and treatment schedules were identical, and the results were pooled for analysis. One hundred twenty eight patients were enrolled. Sixty-five patients received rhGM-CSF in a two-hour intravenous infusion daily for 21 days, starting within four hours of the marrow infusion, and 63 patients received placebo. RESULTS: No toxic effects specifically ascribed to rhGM-CSF were observed. The patients given rhGM-CSF had a recovery of the neutrophil count to 500 x 10(6) per liter 7 days earlier than the patients who received placebo (19 vs. 26 days, P less than 0.001), had fewer infections, required 3 fewer days of antibiotic administration (24 vs. 27 days, P = 0.009), and required 6 fewer days of initial hospitalization (median, 27 vs. 33 days; P = 0.01). There was no difference in the survival rate at day 100. CONCLUSIONS: In patients undergoing autologous bone marrow transplantation for lymphoid neoplasia, rhGM-CSF significantly lessens morbidity. Further studies will be required to establish its optimal dosage and schedule of administration. PMID- 1903850 TI - [Clinical effect of nitroglycerin (GTN) on prevention of cerebral vasospasm]. AB - Nitroglycerin (GTN) is widely used as a safe and effective dilator in patients with ischemic heart disease, and it is said that it dilates the cerebral vessels. So the authors are now using GTN for the prevention of cerebral vasospasm. 125 patients classified as Fisher's Group 2, 3 or 4 were operated on within 72 hours after subarachnoid hemorrhage due to ruptured cerebral aneurysm. 58 patients (GTN group) were treated with continuous intravenous infusions of GTN (0.5-1.0 micrograms/kg/min) for about 2 weeks after their operation, and another 67 patients (control group) were not administered GTN. The frequency of occurrence of symptomatic vasospasm decreased in each GTN group of Fisher's classification, and the severity of angiographic vasospasm also tended to decrease. Especially in patients with severe subarachnoid hemorrhage classified as CT group 3 or 4, symptomatic vasospasm occurred in 11 patients (30.6%) in the GTN group, but in 26 patients (63.4%) in the control group. Regarding the outcome, 10 patients (17.2%) in the GTN group showed poor results or died, as opposed to 22 patients (32.9%) in the control group. This difference was significant. Moreover the GTN group had no cases of mortality due to cerebral vasospasm. These results indicate that GTN can be effective for prevention of cerebral vasospasm and improve the prognosis in patients with serious subarachnoid hemorrhage due to a ruptured aneurysm. PMID- 1903849 TI - [Cost-effectiveness of lowering of blood cholesterol using simvastatin and cholestyramine]. AB - With use of a model of the costs and effects of cholesterol lowering therapy in the primary prevention of coronary heart disease, the cost-effectiveness of simvastatin and cholestyramine in the Netherlands have been estimated. Costs per year of life saved by cholestyramine therapy are several times greater than those of simvastatin therapy and compared unfavorably with those of generally accepted health care programs in the Netherlands. Cholesterol-lowering with simvastatin in men can be cost-effective when therapy is initiated at an early age. At cholesterol levels between 6.5 and 8 mmol/l, however, therapy should be restricted to men with at least one, preferably two additional risk factors such as hypertension or diabetes mellitus. Among women, cholesterol lowering can only be cost-effective when therapy is limited to women with diabetes mellitus or severely elevated serum cholesterol levels. PMID- 1903851 TI - [The effect of repeated occlusions of the middle cerebral artery on pial arterial behavior and cerebral structure]. AB - Temporary clipping of the major arterial trunk is a very important maneuver to control excessive unexpected bleeding during a neurosurgical operation, but repeated temporary clippings sometimes give rise to severe neurological deficits after surgery. In clinical practice, a major stroke can occur after many transient ischemic attacks without distinct angiographic occlusion. To confirm and explain these clinical experiences, the present study was performed. First, 20-min, 30-min and 1-h occlusion of the middle cerebral artery was performed in each of 5 cats, and pial arterial behavior, cerebral edema and infarction were observed. In the 20-min occlusion group, no abnormal change was found 5 hours after recirculation. In the 30-min occlusion group, cerebral edema was present in 10.5 +/- 4.2% of the hemisphere, but no infarction was observed, and pial arterial caliber remained in a 10% dilated state throughout the experimental periods. In the 1-h occlusion group, cerebral edema was present in 41.2 +/- 7.5% of the hemisphere and infarction was found in 34.5 +/- 9.5%. Pial arteries returned to a 20% dilated state but redilated by 45% at the end of experiment. As the second experiment, three 20-min occlusions at 1-h interval and two 30-min occlusions at 1-h interval were performed in each 10 cats. Pial arteries had dilated by 40% after release of the last occlusion in both groups. The extent of cerebral edema was 19.5 +/- 8.1% of hemisphere in the 20-min occlusions group and 36.6 +/- 9.7% in the 30 min occlusions group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1903852 TI - MELAS syndrome. Report of two patients, and comparison with data of 24 patients derived from the literature. AB - We present two unrelated MELAS patients, and compare them with 24 patients derived from the literature. In most patients the stroke-like features of the MELAS syndrome occur late in the course of the disease. The diagnosis is based on characteristic clinical symptoms, presence of lactic acidemia, mitochondriopathy in muscle, and low density lesions on cerebral CT, most frequently occurring in the posterior and parieto-temporal regions. In some cases, a metabolic defect could not be demonstrated, in other cases a partial deficiency of various respiratory chain enzymes was found. PMID- 1903853 TI - Brain single photon emission computed tomography (SPECT) in neuropediatrics. AB - The clinical value in neuropediatrics of [99mTc]HM-PAO brain single photon emission computed tomography was preliminary evaluated by the consecutive investigation of 79 children. Planned epilepsy surgery was the most common indication for the investigation. In 56 children investigated because of epilepsy, SPECT yielded relevant information in 79% of cases examined. The corresponding figures for magnetic resonance imaging and CT were 49% of 35 and 36% of 56 cases, respectively. All 22 children with an epileptic focus, ascertained by freedom from seizures after removal of the area or by consistent neurophysiological and neuroradiological findings, also had abnormal perfusion in the relevant area. Twenty-three children were examined because of neurological signs and symptoms other than epilepsy. SPECT findings were useful for elucidating neonatal brain impairments. Hypoperfused areas in the brain of asphyxiated infants and in posthemorrhagic hydrocephalus corresponded to neuroradiological and autopsy findings. SPECT was found to be an excellent tool when analysing cerebrovascular accidents. In cases with signs and symptoms of a diffuse severe encephalopathy, SPECT did not clarify the etiology but provided information on the distribution of the lesions and probable underlying pathophysiological mechanisms. PMID- 1903854 TI - Primary spontaneous cerebrospinal fluid rhinorrhea. AB - Spontaneous cerebrospinal fluid (CSF) rhinorrhea constitutes only 3% to 4% of CSF fistulas. Nontraumatic, normal pressure CSF fistulas with resultant rhinorrhea, in which no cause can be identified, or primary spontaneous CSF rhinorrhea, is considerably rarer. Presented here are two cases of CSF rhinorrhea of this nature, including the diagnostic workup and treatment. Reviews of literature support laboratory quantitative glucose determination as the most effective and least morbid method for confirming the presence of CSF. Iodine-contrast (metrizamide/lohexol) computerized tomographic cisternography has been shown to be the most effective and least morbid method for localizing the fistula. For inactive, intermittent, small, or questionable CSF leaks, radionuclide cisternography has been shown to be more effective in identifying the presence of these leaks, although not necessarily the location. Numerous reports provide evidence to support the use of an extracranial rhinologic approach for surgical repair of the leak, as a more successful yet less morbid procedure than a craniotomy when used appropriately. PMID- 1903855 TI - Endoscopic diverticulotomy for the treatment of Zenker's diverticulum. AB - First described by Mosher in 1916, endoscopic treatment of Zenker's diverticulum has since been reported infrequently in the surgical literature and continues to engender controversy. Between 1978 and 1989, we treated 11 unselected patients surgically for pharyngoesophageal diverticula. Endoscopic diverticulotomy was used in 11 patients and an external approach was used in the others. The endoscopically treated patients had no serious complications, resumed oral intake early, and were discharged from the hospital earlier. Our review of the surgical literature confirmed our experience with the efficacy and safety of the procedure. We therefore recommend endoscopic diverticulotomy as being equal to external approaches with regard to effectiveness; and it affords the patient a shortened hospital stay and more rapid return to to the premorbid state. PMID- 1903856 TI - A functional evaluation of ansa cervicalis nerve transfer for unilateral vocal cord paralysis: future directions for laryngeal reinnervation. AB - There are a variety of methods for treating unilateral vocal cord paralysis, but to date there are few objective studies that evaluate the functional results of nerve transfer from the ansa cervicalis. Six dogs underwent unilateral recurrent laryngeal nerve section with immediate reanastamosis to the sternothyroid branch of the ansa cervicalis. After 5 to 6 months, measurements of vocal efficiency and acoustic parameters, videolaryngoscopy, videostroboscopy, and evoked electromyography were performed. Identical measurements were made in eight control dogs during normal electrically induced phonation and a simulated unilateral recurrent laryngeal nerve paralysis. Histologic analysis of both vocalis muscles, recurrent laryngeal nerves, ansa cervicalis, and the ansa recurrent laryngeal nerve anastamosis site was performed. Evidence of reinnervation was found in all of the animals that underwent nerve transfer. The vocal efficiency and acoustic quality after ansa cervicalis nerve transfer were dependent on the degree of electrical stimulation from the transferred nerve to the reinnervated cord during phonation. In the absence of electrical stimulation to the nerve transfer, physiologic vocal cord motion could not be elicited from the reinnervated cord. PMID- 1903857 TI - Middle meatus anstrostomy: patency rates and risk factors. AB - Two hundred patients with chronic sinusitis were operated on using functional endoscopic sinus surgery (FESS) techniques. These patients were followed closely over 3 years. Patency of the endoscopic middle meatotomy was recorded using actuarial life-table methods. The overall patency rate of the endoscopic middle meatotomy was 93.55%, and the actuarial patency rate at 36 months was 87.47%. The presence of seasonal allergy with nasal polyps was the most important variable in predicting closure. Middle turbinectomy was the most important variable in predicting patency. Symptoms were evaluated by questionnaire at 1 year. Questionnaire data indicate that 96% of these patients are improved or asymptomatic. PMID- 1903858 TI - Endoscopic surgery for lacrimal obstruction. AB - Intranasal access to the lacrimal drainage system has been greatly enhanced with the advent of endoscopic nasal surgery. This technique has been used for the treatment of recurrent lacrimal obstruction after failed external dacryocystorhinostomy (DCR) in 12 patients. Improved intranasal visualization with the endoscope allowed easy identification and opening of the lacrimal sac, with no need for a skin incision. Obstructing intranasal pathology, including adhesions from previous DCR, an enlarged middle turbinate, and ethmoid sinus disease, was readily identified and corrected. There were no intraoperative complications. Lacrimal obstruction was completely relieved in nine of 12 patients (75%), with a followup of 7 to 25 months. Endoscopic revision DCR should be considered in patients with recurrent epiphora after external DCR. PMID- 1903859 TI - CT evaluation of the paranasal sinuses in symptomatic and asymptomatic populations. AB - The frequency of concha bullosa, paradoxical middle turbinate, and septal deviation on coronal computed tomographic scans evaluating sinus disease is known, but the incidence in normal subjects is unknown. We compared 100 consecutive scans performed for evaluation of sinus disease with 82 consecutive scans performed for evaluation of orbital pathology. Patients with sinus disease had significantly more frequent findings of disease in the osteomeatal complex and all sinuses. Concha bullosa was more common in patients with sinus disease (p less than 0.05), as was septal deviation (p less than 0.01). Paradoxical turbinate was equally common. Concha bullosa was associated with anterior ethmoid disease (p less than 0.04). Septal deviation was associated with osteomeatal complex disease (p less than 0.01) and with anterior (p less than 0.04) and posterior (p less than 0.04) ethmoid disease. Paradoxical turbinate was not associated with sinus abnormalities. These data imply a possible causal relationship between concha bullosa or septal deviation and sinus disease. PMID- 1903860 TI - A rare cause of nasal obstruction: a solitary neurofibroma. AB - This case represents a peripheral nerve sheath tumor as a cause of nasal obstruction. Nerve sheath tumors are relatively uncommon; however, most otolaryngologists will encounter them. These tumors develop from cranial and spinal nerve roots and from peripheral nerves. In total, approximately 25% to 44% of nerve sheath tumors occur in the head and neck region. Although the most important are cranial nerve tumors--the majority being acoustic neuromas arising from the vestibular nerve--they may also develop in the nasal cavity. PMID- 1903861 TI - Quest for the aberrant vessel. AB - In most cases of posterior epistaxis, the terminal branches of the internal maxillary artery (IMA)--principally the sphenopalatine artery--are believed to be the source of hemorrhage. However, we recently treated three patients in which unexpected or aberrant vascular anatomy resulted in persistent posterior epistaxis. PMID- 1903862 TI - Effect of glycerol and mannitol on perilymphatic PO2 in guinea pig cochlea. AB - The effects of glycerol and mannitol on partial oxygen pressure (PO2) in perilymph were studied with a polarographic technique in the guinea pig cochlea. Following a transient reduction immediately after the intravenous injection of each drug, the oxygen tension increased to reach a peak 5 to 10 minutes later, and then decreased gradually. The magnitude and duration of the PO2 increases were larger after the administration of glycerol than after that of mannitol. These results corresponded well with the clinical experience that glycerol was more effective than mannitol in improving hearing in Meniere's disease. The increase of PO2 in the cochlea, therefore, is considered to be one of the possible contributory factors for the improvement of hearing in patients with Meniere's disease after glycerol administration. PMID- 1903863 TI - Prediction of bithermal caloric response from monothermal stimulation. AB - The use of either cold or warm caloric stimulation alone as a screening tool for unilateral weakness has been suggested as a means of both shortening testing time and reducing patient discomfort. The validity of the monothermal caloric test must be well established before it can be routinely used in clinical situations. The purpose of this investigation was to re-evaluate the monothermal caloric test by examining the correlations between unilateral weakness derived from bithermal caloric stimulation compared to monothermal caloric results using either warm or cool stimulation alone. A retrospective analysis of 200 patients indicated significant correlations between bithermal and monothermal unilateral weakness for patients with unilateral weakness of less than 15% and greater than 30% for both warm and cool water stimulation. For patients with 15% to 30% unilateral weakness, the bithermal and monothermal calorics were significantly correlated for only the cool condition. When predicting normal or greater than 20% unilateral weakness, either of the monothermal calorics have greater than 85% efficiency, with specificity greater than 94% and sensitivity greater than 64%. However, the false-negative rate is 29% for warm and 36% for cool calorics. The high rate of false-negative findings indicates that screening tests have no place in a diagnostic battery, especially in view of the implications for missing significant pathology. PMID- 1903864 TI - Skin grafting of the larynx. AB - Skin grafting as a method of restoring the lumen in cases of laryngeal stenosis has been promoted and practiced in the past. Lately, little has been heard of the method. I have personally used skin grafting in almost every case of repair of acute injury or chronic stenosis of the larynx in the last several years. The rationale for grafting is (1) to cover any areas of epithelial loss or dehiscence during the healing period, (2) to reduce the chance of prolonged granulation and subsequent contracture, and (3) to serve as a logical material to use as the interface between a stent and the lumen of the larynx. This report discusses the use of skin grafting in 20 cases of severe acute injury or chronic stenosis. Other procedures needed to enhance the stenotic lumen are also described. In this series, 17 patients are decannulated, one wears a plug continually, and two did not or could not complete the recommended therapy. Among those completing therapy, 100% are either decannulated or wear a plug. PMID- 1903865 TI - The effects of adenotonsillectomy on growth in young children. AB - A history of poor weight gain can often be elicited in young children with chronic upper airway obstruction resulting from adenotonsillar hypertrophy. A series of 41 consecutive children under 3 years of age, who underwent inpatient adenotonsillectomy, were reviewed for changes in weight and height. Thirty-seven patients had adequate long-term follow-up. Of these, many had dramatic improvements in growth after adenotonsillectomy. Indications for surgery in this group were recurrent infection in three patients (7%), unilateral tonsillar mass in one patient (3%), and upper airway obstruction in 37 patients (90%). A clear history of sleep apnea was elicited in 59%. At the time of surgery, 19 of 41 patients (46%) were of the fifth percentile or lower for age-corrected weight. The inpatient hospital stay averaged 3.2 days. The postoperative complication rate was 27%, with postoperative stridor as the most common complication. After surgery, 28 children (75%) showed a change to a higher percentile for weight. Twenty-four (65%) had percentile changes of 15% or more. This change is significant according to results of the Wilcoxon signed-rank test (p less than 0.001). We conclude that a relationship exists between improved growth rate and adenotonsillectomy in our study group. The rapid improvement in growth appears to be most obvious in children with upper airway obstruction resulting from adenotonsillar hypertrophy. Upper airway obstruction (including andenotonsillar hypertrophy) should be suspected as a possible cause in the workup of children with suboptimum growth. PMID- 1903866 TI - The keratitis, ichthyosis, and deafness syndrome. PMID- 1903867 TI - Infectious mononucleosis with airway obstruction and multiple cranial nerve paresis. PMID- 1903868 TI - Sublingual papillary adenocarcinoma: a case report and review of the literature. PMID- 1903869 TI - Congenital varicella and the newborn cry. PMID- 1903870 TI - Emergencies in AIDS patients: the otolaryngologic perspective. PMID- 1903871 TI - Aggressive juvenile fibromatosis involving the paranasal sinuses. AB - Aggressive juvenile fibromatosis is a destructive, locally invasive process, with a propensity for local recurrence after inadequate excision. Although it does not metastasize, uncontrolled growth can eventually lead to death. The role for radiation and chemotherapy is controversial and these modalities are best reserved for advanced unresectable or recurrent lesions. The treatment of choice is en bloc surgical resection with wide margins. PMID- 1903872 TI - The thyroplasty retractor. PMID- 1903873 TI - A dental device for the treatment of obstructive sleep apnea: a preliminary study. PMID- 1903874 TI - Penetration of stimuli of fish skin for Acanthostomum brauni cercariae. AB - The cercaria of Acanthostomum brauni penetrates the skin of its fish host in response to a combination of two chemical signals from the fish skin surface: free fatty acids and a macro-molecular mucus component. The latter seems to be a protein, as the penetration-stimulating activity of fish skin surface mucus is eliminated by digestion with proteinase, but not by digestion with glycosidases, nor by a removal of glycosaminoglycans. These penetration-stimulating host signals differ from the glycoproteins that stimulate the attachment of A. brauni cercariae to the host and also from the macromolecular fish host signals which have been found to stimulate the attachment and penetration by Opisthorchis viverrini cercariae. PMID- 1903875 TI - Proteinases in Trichomonas vaginalis and Tritrichomonas mobilensis are not exclusively of cysteine type. AB - High molecular weight proteinases of Trichomonas vaginalis (with apparent Mr values 142 and greater than 220 kDa) and Tritrichomonas mobilensis (Mr 67, 86, 104 and 120 kDa), optimally active at pH8, were analysed in gelatin-containing polyacrylamide gels. All of these proteinases were resistant to serine-, aspartic as well as cysteine proteinase inhibitors. Both proteolytic bands in T. vaginalis and two proteinases in T. mobilensis (67 and 104 kDa) were inhibited by EDTA and EGTA suggesting that they belong to the metallo-proteinase class. The 67 kDa proteinase of T. mobilensis was inhibited also by o-phenanthroline. The other two bands of T. mobilensis (86, 120 kDa) were not classified to any proteinase group since they appeared to be resistant to the chelating agents tested in this study. PMID- 1903876 TI - Differential regulation of murine Mesocestoides corti infection by bacterial lipopolysaccharide and interferon-gamma. AB - Many liver-invasive parasites cause extensive liver damage which may result in an impaired ability to catabolize endotoxin. The influence of endogenous endotoxin on the progress of liver-invasive parasitic diseases has been investigated in murine Mesocestoides corti infection. Invasion of liver tissue by tetrathyridia resulted in extensive parenchymal destruction with fibrosis. In association with this, undetoxified endotoxin, in potentially biologically active concentration, was found on peritoneal macrophages, 5 months post-M, corti infection. Host susceptibility was influenced by the Lps gene for responsiveness to lipopolysaccharide (LPS). The parasite burden of LPS-responsive (C3H/HeN) mice was significantly increased in the livers of these mice when compared to LPS resistant (C3H/HeJ) mice. LPS reduced the ability of normal peritoneal macrophages to kill tetrathyridia, when co-cultured in vitro. LPS also abrogated the ability of recombinant interferon-gamma (r.IFN-gamma) to enhance macrophage larvicidal activity. These in vitro findings were confirmed in vivo. Daily intraperitoneal administration of LPS, at low concentration, caused a 4-fold increase in parasite burden in the liver, while r.IFN-gamma at optimal concentration reduced parasite burden by 57%. Post-infection macrophages have previously been shown to be refractory to cytokine-activation for larval killing. In this report, we conclude that (1) this refractoriness may be due to the presence of undetoxified endotoxin on post-infection macrophages and (2) endotoxin may reduce host resistance by abrogating effector macrophage response to IFN-gamma. PMID- 1903877 TI - Activation and inhibition of the brush-border membrane-bound alkaline phosphatase activity of Hymenolepis diminuta (Cestoda) by divalent cations. AB - In the absence of exogenous divalent cations, the isolated brush-border plasma membrane of Hymenolepsis diminuta possesses alkaline phosphatase activity (APA). APA is stimulated in the presence of exogenous Mg2+ and inhibited by low concentrations of Zn2+ or high concentrations of Ca2+, and inhibition of APA by Zn2+ is reversed by both Mg2+ and Ca2+. APA is inhibited by ethylenediamine tetraacetic acid (EDTA), ethyleneglycol-bis-(beta-aminoethyl ether) N,N' tetraacetic acid, and 1,10-phenanthroline in time- and concentration-dependent fashions, with EDTA being the most effective inhibitor. Following treatment with EDTA, APA is restored by Mg2+ and, to a lesser extent, by Ca2+, but not by Zn2+. Thus, APA represents a Mg2(+)-dependent enzyme that can be partly activated by Ca2+ but only in the absence of Mg2+. PMID- 1903878 TI - Evidence for widespread occurrence of antibodies to Encephalitozoon cuniculi (Microspora) in man provided by ELISA and other serological tests. AB - The enzyme-linked immunosorbent assay (ELISA) was used to survey human sera for antibodies to Encephalitozoon cuniculi using spores obtained from in vitro cultures as antigen. Sera were obtained from patients with tropical diseases, neurological and renal disorders, patients who were HIV positive and those who had been tested for HIV but found to be negative. Sera from inhabitants of the village of Jali, The Gambia and from healthy blood donors were also examined. Numerous sera from all groups except the blood donors gave positive ELISA reactions at dilutions of 1:400. On titration, those with titres of 1:400 were reclassified as negative. Antibody titres of 1:800 and above were considered to be indicative of past or present infections with E. cuniculi. Many of these ELISA seropositives were also positive by IFAT or PAP. When examined by Western blotting of SDS-PAGE protein profiles of E. cuniculi spores, sera from many patients who had a tropical association reacted with the characteristic profiles shown by known positive mouse and rabbit sera. Others in the tropical group showed antibody binding to some but not all of the immunodominant polypeptides and yet others were negative in spite of their reactivity in the ELISA, IFAT or PAP test. Less agreement between ELISA and Western blotting results was obtained with the other groups of patients, although reactivity with one or more of the major polypeptide bands was sometimes seen. Serum from one blood donor, examined by ELISA and Western blotting, was positive. Differences in the methods of antigen preparation and of epitopes recognized by individuals may account for different reactivities in the tests. It is concluded that infections of E. cuniculi are common in the tropics and that reactivations of these infections might be a hazard to AIDS patients. PMID- 1903879 TI - Schistosoma japonicum: some parameters affecting the development of protective immunity induced by a cryopreserved, irradiated schistosomula vaccine in guinea pigs. AB - Experiments were conducted in guinea-pigs to elucidate the parameters affecting the development of protective immunity against Schistosoma japonicum induced by a cryopreserved, irradiated schistosomula vaccine such as the number of immunizations, route of injection and the use of adjuvants. Results obtained indicated that the cryopreserved, irradiated schistosomula vaccine was effective by either intradermal or intramuscular injection. One intradermal injection with BCG adjuvant resulted in an average worm reduction of 50 x 24%, only a little lower than that of a non-cryopreserved, irradiated vaccine, 53 x 55%, with no statistically significant difference between the two. By intramuscular injection the worm reduction was lower (max. 40%) whether given with or without adjuvants or in 1 or 2 injections. PMID- 1903880 TI - The larvicidal activity of cyclosporin A against Schistosoma mansoni in mice. AB - Treatment of BALB/c or MF1 mice with cyclosporin A (CsA) around the time of infection with Schistosoma mansoni conferred almost complete protection. The migration kinetics of L-[75Se]selenomethionine-labelled infective cercariae were investigated by compressed tissue autoradiography. Similar levels of skin penetration were achieved by cercariae in control and drug-treated individuals. CsA arrested 87-94% of the worms in the skin and ultimately all of these died in this site. Few worms (7-14%) migrated from the skin to the lungs and none completed migration to the liver. Nevertheless, the autoradiograms revealed a limited degree of lateral cutaneous migration by the worms present in the skins of CsA-treated mice. Results of perfusion recovery experiments carried out during the course of infection reinforced the tracking data. PMID- 1903881 TI - Activated macrophages in highly irradiated cercariae-induced immunity to Schistosoma japonicum in rats. AB - The results of studies on the schistosomulicidal activity of activated peritoneal and alveolar macrophages (pM phi and aM phi) from rats immunized with highly irradiated (50 krad.) Schistosoma japonicum cercariae are reported. The authors have examined the activation of these macrophages in terms of spreading, adhesion and ingestion of sheep erythrocytes and pinocytosis of horse-radish peroxidase. Using three criteria, peritoneal macrophages and alveolar macrophages from immunized rats and from rats intraperitoneally injected with BCG were significantly more active than those from normal rats or rats stimulated with 10% proteose-peptone or 1% sodium thioglycolate. A significantly higher percentage of adhesion and ingestion was obtained with the sheep erythrocytes that were co opsonized by heat-inactivated rat anti-sheep erythrocyte serum and fresh normal rat serum. Schistosomulicidal effects were observed with macrophages from irradiated cercariae-immunized rats in two activation systems: in vitro activation in the presence of macrophage-activating factor (MAF), and in vivo activation by the intraperitoneal challenge with sonicated cercarial antigens. PMID- 1903883 TI - [Medical treatment of inflammatory intestinal diseases]. AB - What possible treatments are there for inflammatory intestinal diseases, and on what scientific grounds do we treat these patients? A survey shows that the considerable decline in mortality which has occurred as regards ulcerous colitis ensued rather via trial and error than as a result of regular clinical tests. PMID- 1903882 TI - Factors affecting the intensity of reinfection with Schistosoma haematobium following treatment with praziquantel. AB - Infection with Schistosoma haematobium was studied in a rural community of approximately 500 persons in eastern Zimbabwe. The overall prevalence of infection, as determined by urine egg counts, was 40.1%, and of heavy infections (greater than or equal to 50 eggs/10 ml urine) was 11.0%. The prevalence of both heavy and all infections was highest in the 8 to 10-year-old age class. During 1987-88 data were obtained from 102 individuals on intensity of reinfection 14 weeks after treatment with praziquantel, the efficacy of treatment having been determined after 4 weeks. The water contact made by these individuals during 2 week periods immediately following treatment was recorded. The relative abundance of patent infected intermediate host snails, Bulinus globosus, was also monitored. An index of exposure was developed which weighted each water contact by its duration, the type of activity, the time of day, and the abundance of infected snails at the site used. The relationships between rates of reinfection, rates of exposure, and age were examined. Although only 13 individuals showed positive rates of reinfection, there were statistically significant and independent effects of both exposure and age on reinfection rate. Quantitative estimates of reinfection rates suggested that individuals aged 12 years or less acquired substantially more infection (measured as egg output) than individuals more than 12 years old. PMID- 1903884 TI - Organosulfur compounds of garlic modulate mutagenesis, metabolism, and DNA binding of aflatoxin B1. AB - The effects of two organosulfur compounds of garlic (ajoene and diallyl sulfide) and a crude garlic extract on aflatoxin B1 (AFB1)-induced mutagenesis were determined using rat liver 9,000 g supernatant (S-9) as the activation system and Salmonella typhimurium TA-100 as the tester strain. The effects of these compounds on AFB1 binding to calf thymus DNA were also measured. Metabolites of AFB1 were isolated and analyzed by reverse-phase high-performance liquid chromatography. All these compounds inhibited S-9-dependent mutagenesis induced by AFB1. They also inhibited AFB1 binding to DNA. A significant decrease in organo-soluble metabolites of AFB1 was observed with ajoene and garlic extract. An increase of glucuronide and glutathione conjugates was obtained with garlic extract. The results indicate that garlic compounds tested in this study are antimutagenic and, potentially, anticarcinogenic. PMID- 1903885 TI - Normocytic and macrocytic anemias. AB - Differential diagnosis of normocytic and macrocytic anemias is guided by the patient history, physical examination results, reticulocyte count, and specific red blood cell abnormalities identified on the peripheral smear. In some cases this information is sufficient for diagnosis. When further tests are needed, a stepwise approach, as described by the author, ensures maximum cost-effectiveness without sacrificing diagnostic accuracy. PMID- 1903886 TI - Health risks of foreign travel. Preparing adults for jaunts abroad. AB - Preparing adult travelers for journeys abroad can be challenging and rewarding. Prevention is the cornerstone of a safe, enjoyable trip. Patient education and commonsense precautions may well prevent infection or disease. Prophylaxis for diarrhea and malaria could save one day of illness or inconvenience on an expensive trip or may save a traveler's life. And the Loa loa worm? The nurse fortunately waited until it crawled from under her cornea. Then it was gently teased from under the bulbar conjunctiva. PMID- 1903887 TI - [Degradation of polycyclic aromatic hydrocarbons by a strain of Pseudomonas fluorescens 16N2]. AB - The growth of Pseudomonas fluorescens 16N2 on naphthalene was accompanied with accumulation of salicylate in the culture medium and induction of gentisate 1,2 dioxygenase and catechol 1,2-dioxygenase. The transformation of anthracene by the cells growing on hexadecane led to the formation of 3-hydroxy-2-naphthoate and salicylate. Pathways for naphthalene and anthracene degradation are proposed. PMID- 1903888 TI - [Capnography]. PMID- 1903889 TI - Microbial dehalogenation of 4,4'-dichlorobiphenyl under anaerobic conditions. AB - Anaerobic cultures containing 4,4'-dichlorobiphenyl (4,4'CB) were inoculated with various environmental samples. The degradation of the substrate was followed by gas chromatographic analysis. Three of the cultures tested showed an ability to dehalogenate the substrate, as judged by the presence of 4-chlorobiphenyl and biphenyl in those media inoculated with them. PMID- 1903890 TI - The eel (Anguilla sp) and organic chemical pollutants. AB - The effects of pollutants [pesticides, polychlorinated biphenyls (PCB), hydrocarbons and surfactants] on different species of eel are reviewed. Two types of data are analyzed from the existing literature (72 references), namely those for contaminated waters and those for experiments under laboratory conditions. It is concluded that the eel is not as resistant as has generally been suggested. PMID- 1903891 TI - Polychlorinated biphenyl congeners, hexachlorobenzene and DDTs in human milk in central Italy. AB - The concentration of organochlorine pesticides (hexachlorobenzene, p,p'-DDT and p,p'-DDE) and polychlorinated biphenyl (PCB) congeners in human milk from 56 donors in the hospitals of two Italian towns (Certaldo and Grosseto) are reported. The highest levels found were those of p,p'-DDE, which reached a mean of 2276 ng g-1 at Certaldo and 2270 ng g-1 at Grosseto, p,p'-DDT levels were about an order of magnitude less, with means of 350 and 298 ng g-1, respectively. The DDE/DDT ratio was approximately 8, which is much higher than that found in previous studies. Mean total PCBs were 451 and 295 ng g-1, respectively. About 70% of the PCB residues in the sample analysed consisted of only three congeners: 2,2',4,4',5,5' (IUPAC No. 153), 2,2',3,4,4',5' (138) and 2,2',3,4,4',5,5' (180). PMID- 1903892 TI - [Resistant action of gangliosides on the 6-OHDA injured sympathetic nerves]. AB - A single dose of 6-OHDA (15 mg/kg i.p.) would cause an almost complete disappearance of catecholamine fluorescence in histological preparation of submandibular glands (SMG) 24 hours after injection. Recovery of NA and DA levels went on slowly along with the course of regeneration of the lesioned sympathetic nerve terminals. The NA and the DA contents reached 50% and 28% respectively two weeks after lesion and fully recovered by the end of the fourth week. Gangliosides mixture (GM) (50 mg/kg i.p.) given 0, 4, 8, and 12 hours after 6 OHDA injection could prevent the injury action of NA and DA for at least 24 hours. If this treatment was followed by daily injection for one week, the NA contents remained normal by the end of two weeks. GM treatments beginning either 4 days before or 4 hours after 6-OHDA injection could lessen the extent of decrease of NA and DA by 6-OHDA. The results suggest that: a) GM is effective in protecting the membrane of sympathetic terminals from the injurious effect of 6 OHDA or 6-OHDA metabolites and promoting the regeneration of the lesioned terminals. b) The earlier the GM treatments are given, the better will be the effects. PMID- 1903893 TI - [Inhibitory effect of interleukin-1 beta on follicle stimulating hormone (FSH) induced estrogen production by cultured rat granulosa cells]. AB - Interleukin-1 beta (IL-1 beta), one of the polypeptide lymphokines released in response to antigen, toxins, injury or inflammation by nearly all cell types, has multiple systemic effects. In the present study the effect of IL-1 beta on follicle stimulating hormone (FSH)-induced estrogen production in primary culture was investigated. Granulosa cells obtained from immature estrogen-treated female rats were cultured for 3 days with increasing doses of FSH (1-30 ng/ml) with or without increasing doses of IL-1 beta (2-20 U/ml). The FSH stimulated estrogen production is dose-dependent, whereas IL-1 beta alone did not affect estrogen biosynthesis. In contrast, simultaneous treatment with IL-1 beta caused a dose dependent inhibition of FSH action. This inhibitory effect of IL-1 beta was evident 48 h after the treatment. Furthermore, IL-1 beta inhibited forskolin (10( 5) mmol/L) and (Bu)2 cAMP (10(-2) mmol/L)-stimulated estrogen production, indicating a post-cyclic AMP site of action. The present study suggests that IL-1 beta is a potent modulator of granulosa cell steroidogenesis. Decreased estrogen formation may contribute to the follicle atresia and the impaired reproductive functions during injury and inflammation. PMID- 1903894 TI - [Viral hepatitis C]. PMID- 1903895 TI - [Marginal adaptation of posterior resins: effect of hygroscopic expansion and layer placement technique on Class II and V fillings]. AB - Human teeth were filled with two posterior resins, Heliomolar and P-50, using Gluma as dentin adhesive. After this the teeth were extracted and the author studied the microleakage. The composite filling of the cavities was done following two techniques, one by layers and other with the bulk technique. The teeth were kept in saline solution at 37 degrees C and after 30 days the teeth were studied. The Heliomolar composite was able to avoid the microleakage in almost 100% of the samples independently of the inserting technique used. The P 50 composite was not able to avoid the microleakage unless in a very small number of teeth and this happened only when the layer technique was used. The difference between both is due to the greater amount of organic component in the microfilled resins producing thus a greater higroscopic expansion. PMID- 1903896 TI - Ceftazidime treatment in cystic fibrosis: resistant organisms in sputum and faeces. AB - Ceftazidime was used as the only intravenous agent for treating lower respiratory tract infections in patients with cystic fibrosis. The risks of inducing beta lactamases and conferring antibiotic resistance are high when monotherapy is used; so the emergence of resistant bacteria was studied prospectively in the sputum of 120 patients. The mean age of patients was 9.0 (range 0.3-25) years and there were equal number of male and female patients. Pseudomonas aeruginosa was the only ceftazidime resistant bacterium to be isolated from the respiratory tract, and was identified only in chronically colonised patients. Ceftazidime resistance occurred in 103 (14%) of 750 P aeruginosa isolates, and in 16 of 36 chronically colonised patients. Ceftazidime resistant organisms were isolated from the faeces of 17 of 64 patients investigated. Eighty two per cent of the resistant faecal organisms were single isolates: the same resistant organism in faeces was isolated from successive samples in only two patients. In no case was the ceftazidime resistant enteric isolate the same as that from sputum. Patients chronically colonised by P aeruginosa did not harbour ceftazidime resistant enteric organisms any more than non-colonised patients. The use of ceftazidime as a single intravenous agent in treating chest exacerbations in cystic fibrosis does not induce a reservoir of ceftazidime resistant bacteria. PMID- 1903897 TI - Treatment and control of sarcoptic mange: evaluation of treatment of both the pigs and environment. AB - Pigs in a herd infected with Sarcoptes scabiei var suis were treated with 20% phosmet at a dose rate of 20 mg/kg body weight. In one of the groups the environment was also treated using 2% trichlorphon. Post-treatment clinical examination and parasitological evaluation of skin scrapings revealed complete recovery by the end of the second month after initial treatment with no evidence of reinfection for a period of five months. PMID- 1903898 TI - Modulation of bovine mammary neutrophil function during the periparturient period following in vitro exposure to recombinant bovine interferon gamma. AB - Effects of recombinant bovine interferon (rBoIFN) gamma on mammary gland neutrophil activity during the periparturient period were studied. Bovine mammary gland neutrophils were isolated and incubated in mammary gland secretions obtained from Holstein-Friesian cattle during the last 2 weeks of gestation. Cell functions were evaluated following treatment with 10 U, 100 U, and 1000 U of rBoIFN-gamma. Bacterial phagocytosis, bactericidal activity and chemiluminescence were significantly lower for neutrophils incubated in mammary gland secretions when compared with control neutrophils incubated in Hank's balanced salt solution. Treatment of mammary neutrophils with rBoIFN-gamma reversed the suppressive effects of mammary secretions resulting in higher chemiluminescent activity and significantly more bacterial phagocytosis and bactericidal activity when compared with untreated controls. Results from these preliminary in vitro data suggest that rBoIFN-gamma therapy may modulate mammary gland neutrophil functions in vivo and possibly facilitate the rapid clearance of mastitis-causing pathogens mammary glands during the periparturient period. PMID- 1903899 TI - [Special problems of nutrition therapy in patients with terminal kidney insufficiency with chronic ambulatory hemodialysis]. AB - The treatment of end-stage chronic renal failure with intermittent ambulatory hemodialysis induces additional catabolic stimulus. Thus, the protein requirements of maintainance hemodialysis patients with 1.2 to 1.4 g/kg/day are higher than in the predialysis state. An energy intake of 35 to 38 kcal/kg/day contributes to an optimal anabolic utilization of incorporated protein. The catabolic response in case of complications or stress situations demands supplementation of nutrients. PMID- 1903900 TI - [Percutaneous and interstitial radiotherapy in the function-preserving treatment of laryngeal carcinoma]. AB - Since September 1986 an Ir-192 source with a high dose rate has been used for interstitial boosting of the tumor-bearing vocal cord in the organ-preserving management of larynx carcinoma. The combined percutaneous and interstitial treatment has been administered either as the primary treatment or after incomplete removal of the tumour (stripping). So far 16 patients with 18 vocal cord tumors have been treated. 9 patients presented with a T1-tumour, and 7 patients presented with a T2-stage (2 patients presented with tumours on both cords). All patients refused surgical interventions, 4 of them refused cord stripping too. The treatment method included external radiotherapy with a dose of 4600 to 5000 cGy to the larynx. 1 to 2 weeks after external XRT an interstitial implant into the vocal cord was performed. Using 2 needles per cord, a boost dose of 1000 cGy was given to the tumour area. The median follow-up time is 21.3 months (range 5 to 49, calculated October 1990). So far no local or regional failures occurred. None of the patients had intra- or postoperative complications. All patients have preserved their voice, 2 of them present with a mild hoarseness. Concerning the late effects, 1 patient developed a mild submental edema, 1 patient presents with telangiectasia on the treated vocal cord. The number of patients is very low, but the psycho-social aspects of preserving the ability to speak is of high value. PMID- 1903901 TI - The impact of the Rx to OTC switch on practicing pharmacists. PMID- 1903902 TI - Nonsteroidal anti-inflammatory drugs and antihypertensives. AB - Approximately 60 million people in the United States have hypertension (BP greater than or equal to 140/90 mm Hg), 40 million have arthritis clinically suitable for nonsteroidal anti-inflammatory drug (NSAID) therapy, and millions take NSAIDs for nonarthritic conditions, creating considerable potential for concomitant administration of NSAIDs and antihypertensive agents. It is estimated that more than 20 million people are on concurrent therapy. Most NSAIDs produce mild elevations of normal blood pressure levels and can partially or completely antagonize the effects of many antihypertensive drugs. The effect on blood pressure can vary from no effect to hypertensive crisis. In pooled studies, the average increase in mean arterial pressure was 10 mm Hg, and duration was short lived or chronic. Significant interactions occur in about 1% of patients per year. The risk is greatest in the elderly, blacks, and patients with low-renin hypertension. NSAIDs may block the antihypertensive effects of thiazide and loop diuretics, beta-adrenergic blockers, alpha-adrenergic blockers, and angiotensin converting enzyme inhibitors. No interactions have been reported with centrally acting alpha agonists or the calcium channel blockers. The mechanism of the hypertensive effects of NSAIDs seem primarily related to their ability to block the cyclo-oxygenase pathway of arachidonic acid metabolism, with a resultant decrease in prostaglandin formation. The prostaglandins are important in normal modulation of renal and systemic vascular dilatation, glomerular filtration, tubular secretion of salt and water, adrenergic neurotransmission, and the renin angiotensin-aldosterone system. Blockade of salutary effects of prostaglandins by NSAIDs results in a complex series of events culminating in attenuation of the effects of many antihypertensive agents. High-risk patients treated with NSAIDs should be identified and have blood pressure, renal function, and serum potassium frequently monitored. PMID- 1903903 TI - An in vitro study of the potency and stability of fortified ophthalmic antibiotic preparations. AB - We studied the potency of fortified ophthalmic antibiotic preparations of cefazolin sodium (50 mg/ml) and tobramycin sulfate (15 mg/ml), as measured by the minimum inhibitory concentration, against Streptococcus pneumoniae and Pseudomonas aeruginosa, respectively. We also examined absorbance spectra, pH, and the effect of storage temperature on these fortified solutions to determine their stability over a four-week period. Cefazolin and tobramycin maintained a constant potency throughout the experiment. There was no difference in potency if the fortified solutions were stored at 4 C or 24 C. Cefazolin stored at 24 C exhibited changes in both its absorbance spectra and pH after seven days. Cefazolin stored at 4 C and tobramycin stored at 24 C and 4 C remained stable throughout the four-week period. PMID- 1903904 TI - Magnetic resonance imaging signs of optic nerve gliomas in neurofibromatosis 1. AB - We reviewed the magnetic resonance images of four children with neurofibromatosis 1 and orbital optic gliomas. The images showed double-intensity tubular thickening characteristic of perineural arachnoidal gliomatosis, elongation of the nerves, and downward kinking of the nerves in the midorbit. We believe these findings typify the orbital gliomas in patients with this disease. PMID- 1903905 TI - Delayed allergic reactions to beta-lactams. Four cases with intolerance to amoxicillin or ampicillin and good tolerance to penicillin G and V. AB - We present four cases of delayed allergic skin reactions to amoxicillin or ampicillin with good tolerance to benzyl penicillin and phenoxymethyl penicillin. The clinical symptoms reported by the patients, the intradermal skin tests and the controlled challenge results suggested that the mechanism was cellular mediated. In two patients these findings were supported by histopathological studies. Although delayed-type hypersensitivity reactions to beta-lactams with positive skin test seem rare, they can occur to penicillins in allergic patients. The production of these reactions by amoxicillin or ampicillin with good tolerance to benzyl penicillin and phenoxymethyl penicillin emphasizes the role of the side chain in inducing allergic reactions to beta-lactams. PMID- 1903906 TI - Emergency department screening for syphilis in patients with other suspected sexually transmitted diseases. AB - STUDY OBJECTIVE: To evaluate targeted screening for syphilis among a high-risk group of emergency department patients. STUDY DESIGN AND TYPE OF PARTICIPANTS: During a four-month period, 260 patients with suspected sexually transmitted diseases other than syphilis had rapid plasma reagins drawn to determine the incidence of otherwise unsuspected syphilis. RESULTS: Twenty-two patients (8%) had a reactive rapid plasma reagin. Of these, 16 (6%) also had a reactive FTA-ABS and were determined to have syphilis. The cost for screening was $104.90 for each patient with syphilis. Using Poisson regression to control for changing rates over time and for prior differences in rates of syphilis detection in the three hospitals involved in the study, it was determined that our intervention led to 2.4-fold as many cases identified as would have been expected considering prior rates and the increasing incidence of syphilis. CONCLUSION: Syphilis screening of this high-risk population in the ED is warranted. PMID- 1903907 TI - Use of portable ultrasound to assist urine collection by suprapubic aspiration. AB - STUDY OBJECTIVE: To determine whether portable ultrasound can improve the success rate of suprapubic aspiration (SPA). DESIGN: Patients were randomly assigned to either ultrasound or no ultrasound groups. In the ultrasound group, patients underwent SPA if ultrasound revealed urine in the bladder: if no urine was present, patients underwent catheterization instead of SPA. In the no-ultrasound group, SPA was attempted without ultrasound. All unsuccessful SPAs were followed by catheterization and measurement of urine volume. SETTING: Children's hospital based pediatric emergency department. PARTICIPANTS: Children less than 2 years old who required SPA. INTERVENTIONS: Ultrasound versus no ultrasound. RESULTS: Thirty-five patients were randomized to the ultrasound group, and 31 were randomized to the no-ultrasound group. SPA was successful in 79% of attempts in the ultrasound group compared with 52% in the no-ultrasound group (P = .04). The sensitivity and specificity of ultrasound were 90% and 86%, respectively. CONCLUSION: Portable ultrasound can significantly improve the success rate of SPA and limit nonproductive attempts at SPA. PMID- 1903908 TI - Comparison of operative versus percutaneous endoscopic gastrostomy tube placement in the elderly. AB - To compare techniques of gastrostomy in elderly patients, the records of 100 patients age 70 and older who underwent gastrostomy tube placement as a primary procedure were reviewed. Two separate unmatched groups of 50 patients each were identified: those that underwent operative gastrostomy tube (OGT) placement and those that underwent percutaneous endoscopic gastrostomy tube (PEG) placement. The groups were studied for demographic similarities and for differences in morbidity, mortality, and ease of feeding. Comparison showed that PEGs had a lower mortality (0%) and morbidity (10%) than did OGTs where mortality was 4 per cent and morbidity was 22 per cent. PEGs began feeding sooner (1.0 day vs. 2.8 days) than OGTs. In addition, almost 60 per cent of the PEG patients underwent complete upper endoscopy at the time of the PEG, which revealed pathology that either altered the type of tube placed or the eventual medical management. PEG offers a less morbid, safer, and easier to use method of gastrostomy tube placement than OGT in the majority of elderly patients. PMID- 1903909 TI - The NF1 translocation breakpoint region. AB - The genetic locus that harbors mutation(s) responsible for neurofibromatosis type 1 (NF1) is on chromosome 17, within band q11.2. We have mapped the human homologue of a murine gene (Evi-2) that is implicated in myeloid tumors, to a location between two NF1 translocation breakpoints on chromosome 17. Sequencing studies predict that EVI2 is a membrane protein that may complex with itself and/or other proteins within the membrane, perhaps to function as part of a cell surface receptor. In the course of these studies we have also identified three other transcripts (classes of cDNAs) from the NF1 region. Two of them map between the NF1 translocation breakpoints; the remaining transcript maps just outside this region. The map location implicates these four genes as possible candidates for harboring NF1 mutations. PMID- 1903910 TI - Susceptibility of Neisseria gonorrhoeae to cefpodoxime: determination of MICs and disk diffusion zone diameters. AB - We studied the susceptibilities of 77 strains of Neisseria gonorrhoeae to four antibiotics: cefpodoxime, ceftriaxone, penicillin, and tetracycline. All strains were susceptible to ceftriaxone. Cefpodoxime MICs (range, 0.001 to 0.125 micrograms/ml) were parallel to and approximately four times those of ceftriaxone, and all strains will probably be considered susceptible to cefpodoxime. Disk diffusion zone diameters for cefpodoxime ranged from 35 to 57 mm. Of the strains, 32% were penicillin resistant and 51% were tetracycline resistant (MIC, greater than or equal to 2 micrograms/ml). Susceptibility measurements were consistent for disk diffusion zone diameter and MIC, with an overall agreement of 215 of 225 (96%) for ceftriaxone, penicillin, and tetracycline combined. On the basis of these in vitro data, cefpodoxime should be evaluated in the treatment of gonorrhea. PMID- 1903911 TI - Increase in susceptibility of Pseudomonas aeruginosa to carbapenem antibiotics in low-amino-acid media. AB - The in vitro susceptibility of Pseudomonas aeruginosa PAO1 to carbapenem antibiotics, such as CS-533, was influenced by various concentrations of basic amino acids, i.e., L-lysine, L-histidine, and L-arginine, in agar media. P. aeruginosa PAO1 showed higher susceptibility to carbapenems in minimal medium than it did in rich media such as Mueller-Hinton II agar. The susceptibility was decreased by the addition of a basic amino acid to the minimal medium, whereas it was influenced less by other amino acids. The susceptibility of PAO1 to cephalosporins, piperacillin, quinolones, and gentamicin was not influenced by the addition of a basic amino acid to the minimal medium. A significant change in susceptibility to carbapenems by the addition of a basic amino acid was not observed with D2 protein-deficient mutants of PAO1. Clinical isolates of P. aeruginosa also showed an increase in susceptibility in minimal medium. L-Lysine in minimal medium did not have any influence on the production of D2 protein, beta-lactamases, or penicillin-binding proteins of PAO1 or on the chemical degradation of CS-533. These results strongly indicate that the increase in susceptibility of P. aeruginosa to carbapenems relates to less competition with basic amino acids for permeation through the D2 protein channel of P. aeruginosa. PMID- 1903912 TI - In vitro activity of RP 59500, a semisynthetic injectable pristinamycin, against staphylococci, streptococci, and enterococci. AB - The in vitro activity of RP 59500, a semisynthetic pristinamycin, was compared with the activities of vancomycin, oxacillin, ampicillin, gentamicin, ciprofloxacin, and rifampin against five Staphylococcus species, five Streptococcus species, and four Enterococcus species. For staphylococci, MICs were 0.13 to 1 microgram/ml and the MICs for 90% of the strains tested (MIC90s) were 0.13 to 0.5 microgram/ml; there were no differences between oxacillin susceptible and -resistant strains. For streptococci, MICs were 0.03 to 4 micrograms/ml and MIC90s were 0.25 to 2 micrograms/ml; viridans group streptococci were the least susceptible streptococci. For enterococci, MICs were 0.25 to 32 micrograms/ml and MIC90s were 2 to 4 micrograms/ml; Enterococcus faecalis was the least susceptible. Vancomycin was the only comparative drug with consistent activity against all species of gram-positive cocci. With RP 59500, raising the inoculum 100-fold, lowering the pH of cation-adjusted Mueller-Hinton broth to 5.5, or omitting cation supplementation had little effect on MICs, but 50% serum increased MICs 2 to 4 dilution steps. The differences between MBCs and MICs were greater for staphylococci and enterococci than for streptococci. Time kill studies with 24 strains indicated that RP 59500 concentrations 2-, 4-, and 16-fold greater than the MICs usually killed bacteria of each species at similar rates; reductions in CFU per milliliter were less than those observed with oxacillin or vancomycin against staphylococci and less than those observed with ampicillin against enterococci. RP 59500 antagonized the bactericidal activities of oxacillin and gentamicin against Staphylococcus aureus ATCC 29213 and that of ampicillin against E. faecalis ATCC 29212. Against the latter, combination with gentamicin was indifferent. RP 59500 has a broad spectrum of in vitro activity against gram-positive cocci; combining it with other drugs is not advantageous. PMID- 1903913 TI - Susceptibility of Mycoplasma pneumoniae to several new quinolones, tetracycline, and erythromycin. AB - Mycoplasma pneumoniae (39 strains) was most susceptible to two quinolones, WIN 57273 and sparfloxacin, with MICs for 90% of the strains (MIC90S) of 0.125 and 0.25 micrograms/ml, respectively. It was susceptible to ofloxacin and ciprofloxacin at 2 micrograms/ml and to lomefloxacin and fleroxacin at 4 micrograms/ml. The MIC90 of erythromycin was 0.062 microgram/ml, and that of tetracycline was 1 microgram/ml. PMID- 1903914 TI - Hydrolysis of carbaryl by a Pseudomonas sp. and construction of a microbial consortium that completely metabolizes carbaryl. AB - Two Pseudomonas spp. (isolates 50552 and 50581) isolated from soil degraded 1 naphthol and carbaryl, an N-methylcarbamate pesticide, respectively. They utilized these compounds as a sole source of carbon. 1-Naphthol was completely metabolized to CO2 by the isolate 50552, while the carbaryl was first hydrolyzed to 1-naphthol and then converted into a brown-colored compound by the isolate 50581. The colored metabolite was not degraded, but 1-naphthol produced by the isolate 50581 during the exponential phase of growth was metabolized by the isolate 50552. The two isolates were used to construct a bacterial consortium which completely catabolized carbaryl to CO2. No metabolite was detected in the cell cultures of the consortium. The isolate 50581 harbored a 50-kb plasmid pCD1, while no plasmid was detected in the isolate 50552. The isolated bacteria individually or as a consortium may be used for detoxification of certain industrial and agricultural wastes. PMID- 1903915 TI - Molecular characterization of the nisin resistance region of Lactococcus lactis subsp. lactis biovar diacetylactis DRC3. AB - The nisin resistance determinant of Lactococcus lactis subsp. lactis biovar diacetylactis DRC3 was localized onto a 1.3-kb EcoRI-NdeI fragment by subcloning and interrupting the NdeI site by cloning random NdeI fragments into it; the nisin resistance determinant was then sequenced. The nucleotide sequence revealed a large open reading frame containing 318 codons. Putative transcription and translation signal sequences were located directly upstream from the initiation codon. Immediately downstream of the termination codon was a palindromic region resembling a rho-independent termination sequence. This 957-nucleotide open reading frame and its associated transcription and translation signal sequences were cloned into plasmid-free L. lactis subsp. lactis LM0230 and conferred an MIC of 160 IU of nisin per ml. This level of nisin resistance is equivalent to that of the initial nisin-resistant subclone, pFM011, used for further subcloning in this study. The inferred amino acid sequence would result in a protein with a molecular mass of 35,035 Da. This value was in agreement with the molecular mass of a protein detected after in vitro transcription and translation of DNA encoding the nisin resistance gene, nsr. This protein contained a hydrophobic region at the N terminus that was predicted to be membrane associated but did not contain a typical signal sequence cleavage site. No significant homology was detected when the DNA sequence of the nsr gene and the amino acid sequence of its putative product were compared with other available sequences. When subjected to Southern hybridization, a 1.2-kb DraI fragment encoding the nsr gene did not hybridize with the genomic DNA of the nisin-producing strain L. lactis subsp. lactis 11454. PMID- 1903916 TI - Supraventricular tachycardia: diagnosis and current acute management. PMID- 1903917 TI - Enhanced pulmonary function using dimethylthiourea for twelve-hour lung preservation. AB - Current preservation techniques for lung transplantation limit ischemic time to 6 hours. The purpose of this study was to evaluate the ability of dimethylthiourea, a low molecular weight free radical scavenger, to prolong this interval. An in vivo canine transplantation model was used to assess lung function. At harvest and after circulatory arrest, the donor lung was flushed with modified Euro Collins solution (50 mL/kg). In a blinded fashion, dimethylthiourea (5 g) or saline solution was added to the flush solution at harvest and also infused (20 g over 2 hours) at reimplantation. Harvested lungs were stored for 12 hours at 4 degrees C. Allotransplantation was performed in recipient dogs ventilated with 40% O2. After 1 hour, the contralateral pulmonary artery was ligated, forcing the dog to be dependent on the transplanted lung. Twelve dogs were studied, with 6 randomly assigned to each treatment group in a blinded fashion. Measurements were recorded for 8 hours, keeping the inspired oxygen fraction constant at 0.40. All dimethylthiourea-treated dogs survived the observation period, whereas one third of the dogs that received saline solution died. Dimethylthiourea-treated dogs had significantly greater arterial oxygen tension and significantly less pulmonary vascular resistance compared with control animals. These results suggest that treatment of the lung with a free radical scavenger (dimethylthiourea) improves pulmonary function after reimplantation in a canine model after 12-hour hypothermic storage. PMID- 1903918 TI - Prevention of arrhythmias after noncardiac thoracic operations: flecainide versus digoxin. AB - Cardiac arrhythmias are known complications of thoracic operations. The prophylactic value of flecainide administered as a constant-rate, intravenous infusion (0.15 mg.kg-1.h-1) after a loading dose (2 mg.kg-1) was compared with digoxin (10 micrograms.kg-1 for 12 hours, then 0.25 mg.24 h-1) in a randomized study in 30 patients using Holter monitoring during the first 72 hours after operation. Drug monitoring was performed every day to keep a serum level of flecainide of 200 to 600 ng.mL-1 and a digoxin level of 0.8 to 2 ng.mL-1. Failure, defined as the appearance of atrial fibrillation or flutter or the development of complex ventricular arrhythmias (Lown IVb and V), was observed in one patient in the flecainide group (7%) and in 7 patients in the digoxin group (47%) (p less than 0.05). It is concluded that flecainide is more efficient than digoxin in preventing and treating cardiac arrhythmias after thoracic operations. At the dosage used side effects related to flecainide or digoxin were not observed. PMID- 1903919 TI - Testicular plasmacytoma. A case report with immunohistochemical studies and literature review. AB - Plasmacytomas of the testes are extremely rare tumors, especially when occurring in the absence of a previous or concurrent diagnosis of multiple myeloma. We present a case of solitary testicular plasmacytoma in a 71-year-old man who had no clinical evidence of myeloma. Immunohistochemical stains showed monoclonal cytoplasmic production of IgA-kappa within tumor cells. A summary of the other reported cases of testicular plasmacytoma is presented. Plasmacytoma of the testes, while occasionally manifesting as a solitary, primary lesion, most likely is a precocious, highly unusual manifestation of systemic multiple myeloma. PMID- 1903920 TI - Envelope alteration of Escherichia coli HB101 carrying pEAP31 caused by Kil peptide and its involvement in the extracellular release of periplasmic penicillinase from an alkaliphilic Bacillus. AB - The plasmid pEAP31 contains the colicin E1 kil gene. Peptidoglycan and outer membrane components (lipopoly-saccharide, proteins and phosphatidylethanolamine) decreased concurrently in the envelope fraction from Escherichia coli HB101 carrying pEAP31 during the stationary phase of growth. At almost the same time. D alanine residues in peptidoglycan decreased. The Kil peptide is suggested to affect, directly or indirectly, the turnover of peptidoglycan in stationary phase and, as a result, to cause partial exfoliation of the outer membrane. Periplasmic proteins are liberated from E. coli HB101 (pEAP31) probably because of the exfoliation of outer membrane. PMID- 1903921 TI - Distinct structural specificities for functional coupling of the epidermal growth factor receptor to calcium-signalling versus phospholipase A2 responses. AB - Activation of phospholipase C (PLC), leading to a rise in cytosolic Ca2+, and of phospholipase A2 (PLA2) leading to a release of arachidonic acid, are among the early transmembrane signalling events that have been demonstrated in response to occupancy of the epidermal growth factor (EGF) receptor. The tyrosine kinase activity of the receptor has been shown to be necessary for both of these responses. This requirement for the tyrosine kinase activity could conceivably implicate a role for receptor autophosphorylation in the activation of PLA2. We now demonstrate that coupling of the EGF receptor to PLA2 was not impaired in a deletion mutant (CD126) devoid of the 126 amino acids from the C-terminus which include four major autophosphorylation sites. Functional coupling of the EGF receptor to PLA2 was demonstrated using three different experimental designs: (1) release of [14C]arachidonic acid from prelabelled intact cells. (2) release of [3H]arachidonic acid from prelabelled cells permeabilized with glass beads, and (3) direct measurement of PLA2 enzymic activity in cell-free extracts using an 'in vitro' assay employing exogenous phospholipid substrate. Functional coupling of the EGF receptor to PLA2 occurred despite the absence of a demonstrable Ca(2+) signalling response and the detection of diminished but persistent PLC-gamma phosphorylation on tyrosine residues in the CD126 deletion mutants. These results point to a clear distinction in the biochemical mechanism and role for receptor autophosphorylation in functional coupling of the EGF receptor to PLA2 activation versus Ca2+ signalling. PMID- 1903922 TI - Aminoacetone synthase from goat liver. Involvement of arginine residue at the active site and on the stability of the enzyme. AB - The arginine-specific reagents phenylglyoxal and butane-2,3-dione inactivated goat liver aminoacetone synthase with pseudo-first-order kinetics, with the rate dependent on modifier concentration. Phenylglyoxal and butane-2,3-dione appeared to react with one arginine residue per enzyme molecule. The inactivated enzyme could be re-activated by Tris, suggesting additional evidence of modification of the arginine residue. Acetyl-CoA, one of the substrates, completely protected the enzyme from inactivation. Glycine gave partial protection. Protection by substrates against inactivation by phenylglyoxal and butane-2,3-dione suggested the presence of an essential arginine residue at the substrate-binding region. Experiments with [7-14C]phenylglyoxal in the presence of acetyl-CoA showed that only the arginine residue at the active site could be modified by phenylglyoxal. The stability of the enzyme is dependent on the presence of both EDTA and Mg2+. PMID- 1903923 TI - Redistribution of ADP-ribosylation factor during stimulation of permeabilized cells with GTP analogues. AB - Low-molecular-mass GTP-binding proteins of the ras family were analysed by [32P]GTP binding after PAGE and transfer to nitrocellulose membranes. By this technique, several GTP-binding proteins in the 20-30 kDa range were detected in both cytosolic and microsomal fractions of RINm5F cells. One of these, displaying an apparent molecular mass of about 20 kDa and a pI of 6.7, was mainly cytosolic and was shown to be the ADP-ribosylation factor (ARF) by using specific antibodies. When permeabilized RINm5F cells were incubated with the stable GTP analogues guanosine 5'-[gamma-thio]triphosphate (GTP[S]) and guanosine 5'-[beta gamma-imido]triphosphate (p[NH]ppG) the amount of ARF increased in a fraction containing both Golgi and plasma-membrane markers, but not in the fraction containing secretory granules, mitochondria and lysosomes. GTP, GDP and its beta thio analogue did not enhance ARF binding to membranes, smg25/rab3 and rho, as well as all the other small GTP-binding proteins detected by the [32P]GTP binding, did not redistribute under these conditions. As GTP[S] stimulates insulin secretion in these cells, we also examined the relationship between ARF translocation and insulin secretion. Both phenomena were elicited by GTP[S] with an EC50 (median effective concentration) of about 10 microM. p[NH]ppG was equipotent with GTP[S] in inducing insulin secretion (EC50 about 10 microM), but higher concentrations (about 500 microns) were required to achieve the same maximal ARF redistribution. These results suggest that: (1) ARF is subject to cycling between a membrane-associated and a free/loosely attached form, determined by the species of bound guanine nucleotide; (2) ARF alone does not seem to regulate exocytosis in insulin-secreting cells. PMID- 1903924 TI - Interactions of purified bovine brain A1-adenosine receptors with G-proteins. Reciprocal modulation of agonist and antagonist binding. AB - The bovine brain A1-adenosine receptor was purified 8000-fold by affinity chromatography on xanthine-amine-congener (XAC)-Sepharose. Addition of a 120-fold molar excess of a purified bovine brain G-protein preparation (Go,i a mixture of Go and Gi, containing predominantly Go) decreases the Bmax of the binding of the antagonist radioligand [3H]XAC to the receptor. This decrease is observed not only after insertion into phospholipid vesicles but also in detergent solution, and is reversed by GTP analogues. In the presence of Go,i, about 20 and 40% of the receptors display guanine-nucleotide-sensitive high-affinity binding of the agonist radioligand (-)-N6-3-([125I]iodo-4-hydroxyphenylisopropyl)adenosine after reconstitution into lipid vesicles and in detergent solution, respectively. The ability of Go,i to enhance agonist binding and decrease antagonist binding is concentration-dependent, with a half-maximal effect occurring at approximately 10 fold molar excess of G-proteins over A1-adenosine receptors. In the presence of the receptor, the rate of guanosine 5'-[gamma-[35S]thio]triphosphate (GTP[35S]) binding to Go,i is accelerated. This rate is further enhanced if the receptor is activated by the agonist (-)(R)-N6-phenylisopropyladenosine, whereas the antagonist XAC decreases the association rate of GTP[35S] to levels observed in the absence of receptor. These results show (1) that detergent removal is not a prerequisite for the observation of coupling between the A1-adenosine receptor and Go,i, and (2) that the regulatory effect of G-proteins on antagonist binding to the A1-adenosine receptor can be reconstituted by using purified components. PMID- 1903925 TI - Mucins in cat airway secretions. AB - Mucous secretions were obtained from cat tracheas that had received [3H]glucose and [35S]sulphate to radiolabel mucus glycoproteins biosynthetically. Samples were collected under resting ('basal') conditions as well as after pilocarpine stimulation and were separated into gel and sol phases by centrifugation. Macromolecules were partially purified by using gel chromatography on Sepharose CL-4B, and the species that were eluted with the void volume were then separated into two major populations with isopycnic density-gradient centrifugation in CsCl. The major component from the gel phase of pilocarpine-induced secretions had a buoyant density typical of mucins and was observed as linear and apparently flexible chains by electron microscopy. Reduction of disulphide bonds gave subunits that could be further cleaved by trypsin digestion into components of approximately the same size as the high-Mr glycopeptides obtained from other mucins after this treatment. In contrast, the dominant species in the gel phase of the 'basal' secretion had a significantly higher buoyant density than expected for mucins and was largely unaffected by reduction, as studied by gel chromatography. The macromolecules were fragmented by trypsin, suggesting that they contain a polypeptide backbone. This more dense component also predominated in the sol phase both from the 'basal' secretions and from the pilocarpine released secretions. Digestion with DNAase, chondroitin ABC lyase or heparan sulphate lyase had no effect, which shows that this component is not DNA, a dermatan sulphate/chondroitin sulphate or a heparan sulphate proteoglycan. In contrast, endo-beta-galactosidase and keratanase caused some fragmentation, suggesting that the molecules contain some linkages of the poly-(N-acetyl lactosamine) type, although the degradation was not as extensive as expected for keratan sulphate. Treatment with alkaline borohydride resulted in extensive fragmentation of the high-Mr glycopeptides from both components, indicating that the glycans were oligosaccharides that were probably O-linked. The monosaccharide compositions of both components were consistent with that expected for mucins. The data are in keeping with the major component from the pilocarpine-stimulated gel secretions being a mucus glycoprotein and the more dense component being a mucin-like molecule, possibly related to the keratanase-sensitive material isolated from canine trachea by Varsano, Basbaum, Forsberg, Borson, Caughey & Nadel [(1987) Exp. Lung Res. 13, 157-184]. PMID- 1903926 TI - The octameric structure of beta-glucosidase from Botryodiplodia theobromae Pat. AB - 1. Whereas only beta-glucosidase A (beta-D-glucoside glucohydrolase, EC 3.2.1.21) was produced by the tropical fungus Botryodiplodia theobromae Pat. (I.M.I. 115626; A.T.C.C. 26123) in young cultures containing D-cellobiose as carbon source, lower-Mr forms (B, C and D) were found in older cultures when the pH had drifted from the initial value of pH 6.2 to pH 7.9. 2. The Michaelis constants (Km) of the various molecular forms of the enzyme were 0.30 +/- 0.03 mM-, 0.26 +/ 0.01 mM-, 0.20 +/- 0.02 mM- and 0.16 +/- 0.01 mM-o-nitrophenyl beta-D glucopyranoside for beta-glucosidase forms A (Mr 320,000), B (Mr 160,000), C (Mr 80,000) and D (Mr 40,000) respectively. 3. Only beta-glucosidase D showed substrate inhibition. 4. Only L-arginine was found as the N-terminal residue, and beta-glucosidase A contained 31.7 +/- 0.6 mol of N-terminal L-arginine/mol of the enzyme. 5. Storage of purified beta-glucosidase A under mildly alkaline conditions caused its dissociation into the lower-Mr forms, whereas adjustment of the pH of a solution of beta-glucosidase A to pH 12.0 with 1 M-NaOH led to complete inactivation on incubation at 40 degrees C for 1 h and to the release of 25.2 +/- 1.5 mol of inorganic phosphate/mol of the enzyme. 6. O-Phospho-L-serine was isolated from the acid-hydrolysis product of beta-glucosidase A but not from that of beta-glucosidase D. 7. Reduction and carboxamidomethylation of the various forms of beta-glucosidase gave only one enzymically inactive protein with an Mr of 10,000-11,000. 8. After partial succinylation (3-carboxypropionylation) of beta-glucosidase D at pH 5.0 and removal of the precipitated protein formed, the supernatant solution contained beta-glucosidase components similar to the other molecular forms (A, B and C) and an aggregate (beta-glucosidase Xs) that gave a positive result in the alkaline hydroxylamine test, whereas N-succinylated beta-glucosidase D, an aggregate (form Xp) that behaved like beta-glucosidase Xs and traces of forms A, B and C were found by gel filtration of the solution of the precipitate solubilized at neutral pH (7.0-7.7). 9. These observations are discussed in terms of the proposed octameric structure of beta-glucosidase A based on the result of electron microscopy [Umezurike (1975) Biochem. J. 145, 361 368]. PMID- 1903928 TI - Phosphonate monoester inhibitors of class A beta-lactamases. AB - Phosphonate monoesters with the general structure: [formula: see text] are inhibitors of representative class A and class C beta-lactamases. This result extends the range of this type of inhibitor to the class A enzymes. Compounds where X is an electron-withdrawing substituent are better inhibitors than the unsubstituted analogue (X = H), and enzyme inhibition is concerted with stoichiometric release of the substituted phenol. Slow turnover of the phosphonates also occurs. These observations support the proposition that the mechanism of action of these inhibitors involves phosphorylation of the beta lactamase active site. The inhibitory ability of these phosphonates suggests that the beta-lactamase active site is very effective at stabilizing negatively charged transition states. One of the compounds described also inactivated the Streptomyces R61 D-alanyl-D-alanine carboxypeptidase/transpeptidase. PMID- 1903927 TI - A mechanism for differential release of acrosomal enzymes during the acrosome reaction. AB - To study the organization of fertilization enzymes in the sperm acrosome, we isolated and characterized two physicochemically distinct acrosomal fractions of guinea-pig spermatozoa. A soluble fraction contained the 25,000-Mr acrosomal autoantigen, AA1, and most of the acrosomal hyaluronidase and dipeptidyl peptidase II activity. A particulate fraction, designated acrosomal matrix (AM), consisted of membraneless crescent-shaped structures, and contained most of the acrosomal proacrosin. The AM also contained a 28,000-Mr putative proacrosin binding protein, and a very-high-Mr component which, on reduction, was dissociated into 48,000-Mr and 67,000-Mr subunits. Autoproteolytic dissolution of the AM correlated with proteolysis by acrosin of the 28,000-Mr and 48,000-Mr AM molecules. Components of both the AM and the soluble fraction were localized by immuno-electron microscopy to the electron-dense region of the guinea-pig sperm acrosome. We conclude that acrosomal molecules are segregated into soluble and matrix compartments. This segregation is a function of disulphide bonding and non covalent interactions among the relatively few components of the AM. Association of acrosin with the AM may be the mechanism by which this enzyme's release from the spermatozoon during the acrosome reaction is delayed relative to the release of other acrosomal molecules. PMID- 1903929 TI - A sequence similarity between proteins involved in initiation and termination of bacterial chromosome replication. PMID- 1903930 TI - A continuous fluorescence-displacement assay for triacylglycerol lipase and phospholipase C that also allows the measurement of acylglycerols. AB - A new continuous fluorescence-displacement assay for enzymes that release long chain fatty acids [Wilton (1990) Biochem. J. 266, 435-439] is described in detail for pig pancreatic triacylglycerol lipase. The assay involves the displacement of the highly fluorescent fatty acid probe 11-(dansylamino)undecanoic acid from rat liver fatty acid-binding protein by long-chain fatty acids released as a result of enzyme activity. The assay is surprisingly effective for triacylglycerol lipase, allowing the expression of full activity with low concentrations of substrates in the absence of detergents. The initial rate of decrease in fluorescence is linearly related to enzyme concentration, and activity can be detected in the assay down to concentrations of 10 pg of pure enzyme/ml. The assays demonstrated the quantitative conversion of limiting amounts of substrate into the monacylglycerol. This observation allowed the assay to be used to measure substrates such as triacylglycerols and particularly 1,2-diacylglycerols at concentrations down to about 0.1 microM. Because phospholipase C releases 1,2 diacylglycerols, the coupling of this enzyme to excess lipase allowed the measurement of pure phospholipase C from Bacillus cereus at concentrations down to about 2 ng/ml, and the initial rate of fall in fluorescence in the assay was linearly related to enzyme activity. PMID- 1903931 TI - Uptake and degradation of human low-density lipoprotein by human liver parenchymal and Kupffer cells in culture. AB - The association with and degradation by cultured human parenchymal liver cells and human Kupffer cells of human low-density lipoprotein (LDL) was investigated in order to define, for the human situation, the relative abilities of the various liver cell types to interact with LDL. With both human parenchymal liver cells and Kupffer cells the association of LDL with the cells followed saturation kinetics which were coupled to LDL degradation. The association of LDL (per mg of cell protein) to both cell types was comparable, but the association with human Kupffer cells was much more efficiently coupled to degradation than was the case in parenchymal cells. The capacity of human Kupffer cells to degrade LDL was consequently 18-fold higher (per mg of cell protein) than that of the human parenchymal liver cells. Competition studies showed that unlabelled LDL competed efficiently with the cell association and degradation of 125I-labelled LDL with both parenchymal and Kupffer cells, while unlabelled acetyl-LDL was ineffective. The degradation of LDL by parenchymal and Kupffer cells was blocked by chloroquine and NH4Cl, indicating that it occurs in the lysosomes. Binding and degradation of LDL by human liver parenchymal cells and human Kupffer cells appeared to be completely calcium-dependent. It is concluded that the association and degradation of LDL by human Kupffer and parenchymal liver cells proceeds through the specific LDL receptor, whereas the association of LDL to Kupffer cells is more efficiently coupled to degradation. The presence of the highly active LDL receptor on human Kupffer cells might contribute significantly to LDL catabolism by human liver, especially under conditions whereby the LDL receptor on parenchymal cells is down-regulated. PMID- 1903932 TI - Angiotensin II-induced phosphatidylcholine hydrolysis in cultured vascular smooth muscle cells. Regulation and localization. AB - In cultured vascular smooth-muscle cells (VSMC), angiotensin II (AngII) induces a biphasic, sustained increase in diacylglycerol (DG) of unclear origin. To determine whether hydrolysis of phosphatidylcholine (PC) is a possible source of DG, we labelled cellular PC with [3H]choline, and measured the formation of intra and extra-cellular [3H]choline and [3H]phosphocholine after stimulation with AngII. AngII induced a concentration-dependent release of choline from VSMC that was significant at 2 min and was sustained over 20 min. In contrast, accumulation of choline inside the cells was very slight. AngII also increased the formation of [3H]myristate-labelled phosphatidic acid, and, in the presence of ethanol, of [3H]phosphatidylethanol, characteristic of a phospholipase D (PLD) activity. Extracellular release of choline was partially inhibited by removal of extracellular Ca2+ (54 +/- 9% inhibition at 10 min) or inhibition of receptor processing by phenylarsine oxide (79 +/- 8% inhibition at 20 min). The protein kinase C activator phorbol myristate acetate also stimulated a large release of choline after a 5 min lag, which was unaffected by the Ca2+ ionophore ionomycin, but was additive with AngII stimulation. Down-regulation of protein kinase C by a 24 h incubation with phorbol dibutyrate (200 nM) decreased basal choline release, but had no effect on AngII stimulation. We conclude that AngII induces a major PC hydrolysis, probably mainly via PLD activation. This reaction is partially dependent on Ca2+ and is independent of protein kinase C, and appears to be mediated by cellular processing of the receptor-agonist complex. Our results are consistent with a preferential hydrolysis of PC from the external leaflet of the plasmalemma, and raise the possibility that PC hydrolysis occurs in specialized 'signalling domains' in VSMC. PMID- 1903933 TI - Alterations in G-protein expression and the hormonal regulation of adenylate cyclase in the adipocytes of obese (fa/fa) Zucker rats. AB - Attenuated maximal activations by forskolin, Mn+. NaF or guanosine 5'-[gamma thio]triphosphate (GTP[S]) were noted for adenylate cyclase activity in adipocytes from obese (fa/fa) Zucker rats compared with their lean (Fa/Fa) littermates. GTP[S] achieved half-maximal activation of adenylate cyclase at some 10-fold lower concentrations in membranes from lean animals compared with those from obese. Levels of the 42 and 45 kDa forms of Gs were some 40-50% lower in membranes from obese animals, and levels of Gi-1 and Gi-3 were some 62-65% lower. No differences in levels of Gi-2 alpha-subunits or G-protein beta-subunits were observed. Gi function, as assessed by inhibiting forskolin-stimulated adenylate cyclase, achieved by prostaglandin E1, nicotinate and phenylisopropyladenosine, was similar in membranes from both lean and obese animals. Levels of beta adrenoceptors were some 50% lower in membranes from obese animals. It is suggested that the attenuated activation of adenylate cyclase by stimulatory ligands in membranes from obese animals may be caused by decreases in both Gs and receptors, and that this may contribute to the attenuated lipolytic response seen in adipocytes from such animals. PMID- 1903934 TI - Interleukin-1 beta-induced changes in the kinetic constants of L-proline uptake in human skin fibroblasts. AB - The effects of interleukin-1 beta (IL-1) on L-proline uptake in human skin fibroblasts were investigated. Exposure of the fibroblasts to IL-1 (5, 10 or 50 pg/ml) for 2 h did not change L-proline uptake. In contrast, inhibition was observed after 6 h of IL-1 treatment, and only 60% of the control uptake remained after incubation for 24 h with 10 pg of IL-1/ml. IL-1 depressed the activity of both transfer systems; the low-affinity system inhibited by alpha (methylamino)isobutyric acid (Me-AIB), corresponding to system A, and a high affinity transfer system which is unaffected by Me-AIB. The inhibitory effect increased as the L-proline concentration decreased. To determine whether IL-1 induced prostaglandin release influences proline uptake, indomethacin (14 microM) was added as a cyclo-oxygenase inhibitor. Indomethacin itself decreased L-proline uptake but to a lesser extent than did IL-1. When IL-1 was tested in the presence of indomethacin, the inhibition of L-proline uptake was still observed, with values between those obtained with each substance in isolation. This suggests that the inhibitory effect of IL-1 on proline uptake by skin fibroblast does not only involve the prostaglandins that accumulate in the medium, but no firm conclusion can be drawn, due to the fact that the inhibition by the two agents was not statistically independent. Kinetic analyses for 1 min combined with inhibition experiments showed that IL-1 induced a decrease in the Km and Vmax, values of the high-affinity transport system, whereas it increased the Km of system A. Therefore the two systems of proline uptake in skin fibroblasts are probably inhibited by IL-1 via different mechanisms. PMID- 1903935 TI - Characterization of Ca(2+)-dependent endogenous phosphorylation of 160,000- and 150,000-Dalton proteins of sarcoplasmic reticulum. AB - The 160 and 150 kDa proteins of sarcoplasmic reticulum (SR) are phosphorylated endogenously. The phosphorylation of both proteins has a marked requirement for Ca2+. Half-maximal and maximal phosphorylation was obtained at about 1 nM- and 1 microM-Ca2+ respectively, and a Hill coefficient of about 0.5 was calculated. The phosphorylation is also dependent on NaF as an inhibitor of the SR phosphoprotein phosphatase. The phosphorylation of these proteins is very rapid, and maximal phosphorylation is achieved in less than 15 s. The phosphorylation of the 160 kDa and 150 kDa polypeptides is completely inhibited by 5 mM-MgCl2 and by 75 microM LaCl3, by very low concentrations of different detergents, and by preincubation of the SR for 2 min at 60 degrees C. The inhibition by Mg2+ is due to stimulation of ATP hydrolysis, thereby decreasing ATP concentration. Different phosphorylated peptides were obtained by digestion with protease V8 of the 160 kDa and 150 kDa protein bands, suggesting that the 160 kDa and 150 kDa proteins are distinct. The two phosphorylated proteins are present in different fractions and preparations of SR, with or without [3H]PN200-110 binding capacity. These and other results suggest that the phosphorylated SR proteins are distinct from the alpha 1 and alpha 2 subunits of the voltage-gated Ca2+ channel of the T-system membranes. Different inhibitors and activators of protein kinase C and calmodulin-dependent protein kinase have no effect on the endogenous phosphorylation of both polypeptides, suggesting that the phosphorylation is regulated solely by Ca2+. A possible regulatory function for this phosphorylation system is described in the accompanying paper [Gechtman. Orr & Shoshan-Barmatz (1991) Biochem. J. 276.97 102]. PMID- 1903936 TI - Mono-ADP-ribosylation of Gs by an eukaryotic arginine-specific ADP ribosyltransferase stimulates the adenylate cyclase system. AB - An arginine-specific ADP-ribosyltransferase, named ADP-ribosyltransferase A, was partially purified from human platelets using polyarginine as an ADP-ribose acceptor. When human platelet membranes were incubated with the transferase A in the presence of NAD+, Gs, a stimulatory guanine nucleotide-binding protein of the adenylate cyclase was specifically mono-ADP-ribosylated. ADP-ribose transfer to Gs by this enzyme was suppressed when membranes were pre-ADP-ribosylated by cholera toxin. Incubation of membranes with the transferase A resulted in activation of the adenylate cyclase system. This stimulatory effect of the transferase A on the adenylate cyclase system was inhibited by the presence of polyarginine. These results indicate a role of ADP-ribosyltransferase A in regulation of the adenylate cyclase system via endogenous mono-ADP-ribosylation of Gs. PMID- 1903937 TI - Sulfhydryl groups are involved in the interaction of FSH with its receptor. AB - FSH has recently been reported to possess thioredoxin-like activity, presumably explained by the homology between a region of FSH-beta subunit and the active site of thioredoxin. The homologous sequence lies within a receptor binding region, which suggests a possible role for sulfhydryl groups in the formation of an active hormone-receptor complex and subsequent signal transduction. In order to determine the relevance of sulfhydryl groups on FSH-receptor interaction, we studied the effect of N-ethylmaleimide (NEM) and glutathione on FSH binding. The results indicate that free sulfhydryl groups, probably derived from the FSH receptor, are involved in ligand-receptor interaction. PMID- 1903938 TI - Genomic structure and expression of human beta-1,4-galactosyltransferase. AB - We have cloned 60 kilobases of overlapping human genomic DNA comprising the complete coding sequence of the biosynthetic enzyme beta-1,4 galactosyltransferase (GalTase). The human locus spans greater than 50 kb of genomic DNA and shows an exon structure similar to the mouse gene. However, contrary to the mouse and bovine systems, which yield two distinct transcripts, RNA blotting and RNase protection analysis of human mRNA derived from HeLa cells reveal only a single transcript, corresponding to the "short" form of the mouse and bovine transcripts. Furthermore, Northern analysis on a panel of human cell lines of varying tissue origin and morphology shows GalTase expression levels to be highly variable, consistent with the notion that GalTase expression and consequent cell-specific differences in galactosylation are at least partially regulated at the transcriptional level. PMID- 1903939 TI - Lysolecithin--a potent activator of prophenoloxidase from the hemolymph of the lobster, Homarus americanas. AB - The phenoloxidase system, which is involved in encapsulation and melanization of foreign objects in crustacean, is found to be present in an inactive proenzyme form in the hemocytes of the lobster, Homarus americanas. Activation of the enzyme could be achieved either by treatment with an anionic detergent such as sodium dodecyl sulfate, or by a cationic detergent such as cetylpyridinium chloride, but not by either nonionic detergent or zwitterionic detergent. In addition, a number of fatty acids also activated the proenzyme. However, phospholipids, especially lysolecithin proved to be the most potent activator of prophenoloxidase. Therefore, it is proposed that apart from the well established proteolytic mode of activation, prophenoloxidase can also be activated by this alternative mode involving lipids. PMID- 1903940 TI - Intraperoxisomal form of alanine:glyoxylate aminotransferase in the peroxisomes of bird kidney. AB - Alanine:glyoxylate aminotransferase has been reported to be present as the apo form in the peroxisomes and as the holo form in the mitochondria in chicken kidney. In contrast, the enzyme was found to be present as the holo form both in the peroxisomes and in the mitochondria in pigeon kidney, suggesting that birds are classified into two groups on the basis of intraperoxisomal form of kidney alanine:glyoxylate aminotransferase. In the kidney, the pigeon peroxisomal holo enzyme did not cross-react immunologically with the chicken peroxisomal apo enzyme. PMID- 1903941 TI - GTP-dependent membrane fusion during hepatocarcinogenesis and liver regeneration. AB - Rough microsomes were isolated from homogenates of livers of rats bearing hepatomas as well as from homogenates of livers of rats 24 and 48 h after partial hepatectomy. When incubated in the presence of GTP in a cell-free system to assay membrane fusion these membranes were observed to have a greater capacity (1.4 to 5 fold) for GTP-dependent fusion than homologous membranes from control non proliferating liver tissue. The enhanced GTP-dependent membrane fusion may reflect changes in membrane properties related to cell proliferation. PMID- 1903942 TI - Enhanced contractile effect of phorbol dibutyrate in portal veins from hypertensive rats. AB - The effects of phorbol 12,13-dibutyrate (PDBu) on portal veins from hypertensive (SHRSP0 and normotensive (WKY) rats were examined. PDBu contracted the strips from SHRSP and WKY in a concentration-dependent manner. However, both twitch contraction and tonic contraction of strips in response to PDBu were enhanced in SHRSP. Treatment with staurosporine reduced contractile response to PDBu in strips from SHRSP. It appears that the activity of protein kinase C in vascular smooth muscle is increased in SHRSP. PMID- 1903943 TI - Phosphorylation of the stress protein hsp27 is an early event in murine myelomonocytic leukemic cell differentiation induced by leukemia inhibitory factor/D-factor. AB - Leukemia inhibitory factor/D-factor, a potent differentiation-inducing glycoprotein for murine myelomonocytic leukemic M1 cells, rapidly stimulated the phosphorylation of a 27 kDa protein with an isoelectric point of 5.6 in a LIF sensitive M1-T22 cell line but not in a LIF-resistant M1-D(-) cell line. The increase in phosphorylation was detectable 5 min after LIF treatment and was maximal at 10 min. Heat shock treatment at 44.5 degrees C for 30 min also induced the phosphorylation of the same 27 kDa protein. Although this 27 kDa protein did not become labeled with [35S]-methionine, metabolic labeling experiments using [35S]-cysteine or [3H]-leucine clearly demonstrated that the synthesis of this protein was enhanced after heat shock. These results suggest that the phosphorylated 27 kDa protein is a low molecular weight stress protein and that the protein may play a role at an early stage in the LIF signaling pathway probably linked to macrophagic differentiation. PMID- 1903944 TI - Phosphorylation of only serine-51 in protein synthesis initiation factor-2 is associated with inhibition of peptide-chain initiation in reticulocyte lysates. AB - We have examined the phosphorylation of the alpha-subunit of initiation factor-2 (eIF-2 alpha) in reticulocyte lysates in which translational shut-off was induced by haem-deficiency or by double-stranded RNA. To maximise the phosphorylation of eIF-2 alpha, lysates were supplemented with the broad spectrum phosphatase inhibitor microcystin. Under all conditions tested, serine-51 was the only residue to become labelled. This is consistent with the observation of only two species of eIF-2 alpha in isoelectric focusing/immunoblotting analyses of lysates treated as described above. PMID- 1903945 TI - Acyclonucleoside analogue inhibitors of mammalian purine nucleoside phosphorylase. AB - A series of about 60 purine acyclonucleosides, most with guanine as the aglycone and a 4-carbon chain as the acyclic moiety, was examined for ability to inhibit purine nucleoside phosphorylase from human erythrocytes and calf spleen. Compounds with shorter and longer acyclic chains were less effective inhibitors. Synthetic procedures are described. About 25 of the analogues were competitive inhibitors (relative to inosine or 7-methylguanosine as substrates) with Ki values in the range of 2 to 100 microM. The more potent ones (Ki 2-5 microM) included guanine as the aglycone, with various substituents at C(2') of the acyclic chain and hydroxyls at C(3') and C(4'). In one instance, 9-(2-fluoro-3,4 dihydroxybutyl)guanine, the (+)erythro enantiomer was 10-fold more effective than its (-) counterpart (2.5 microM vs 27 microM). Replacement of guanine by 8-bromo- or 8-aminoguanine enhanced affinity for the enzyme by an order of magnitude or more; 7-deazaacyclovir was also 10-fold more effective than acyclovir. With some of the inhibitors, Ki (human)/Ki (calf) varied over the range 0.4 to 4, reflecting differences between the two enzymes; nonetheless, the much more stable, and commercially available, calf spleen enzyme is recommended for preliminary screening of potential inhibitors of the human or other unstable enzymes. The overall results provide useful indications for the synthesis of potentially more potent inhibitors of the enzyme, by simultaneous modifications of the aglycone and the acyclic chains. PMID- 1903946 TI - Purification and characterization of 5'-deoxy-5'-methylthioadenosine (MTA) phosphorylase from human liver. AB - 5'-Methylthioadenosine phosphorylase was purified 8000-fold from human liver using a combination of affinity chromatography, chromatofocusing and gel filtration. A 25% overall yield was obtained. The specific activity of the final preparation was 40 mumol of 5'-methylthioadenosine cleaved per hr per mg of protein. The enzyme had an apparent molecular weight of 55,000 daltons, as determined by gel filtration of Superose 12 and Sephadex G-150, with a subunit molecular weight of 30,000 daltons, as determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis. The substrate specificity of the purified enzyme was studied in both the direction of nucleoside cleavage and nucleoside synthesis. PMID- 1903948 TI - Dihydroisoquinolinones: the design and synthesis of a new series of potent inhibitors of poly(ADP-ribose) polymerase. AB - A series of dihydroisoquinolinones, formally rigid analogs of 3-substituted benzamides, and a series of 2,3-disubstituted benzamides were synthesized and evaluated as inhibitors of poly(ADP-ribose) polymerase. The results indicated that the orientation of the amide with respect to the substituent on the aromatic ring was critical for optimum inhibitory activity. Selected compounds were also evaluated for their ability to modify the radiation response of mammalian cells to ionizing radiation. A number of the 5-substituted dihydroisoquinolinones, which were very potent inhibitors of the enzyme, were able to enhance the lethal effects of ionizing radiation in mammalian cells, as measured by changes in the survival curve parameters Do and/or Dq. PMID- 1903947 TI - Glycogen phosphorylase in the fat body of two cockroach species, Periplaneta americana and Nauphoeta cinerea: isolation, partial characterization of three forms and activation by hypertrehalosaemic hormones. AB - The presence of endogenous phosphorylase kinase and phosphorylase phosphatase in crude extracts of fat bodies from the cockroaches Nauphoeta cinerea and Periplaneta americana is demonstrated in vitro by activation/inactivation of glycogen phosphorylase under appropriate conditions. Fractionation of fat body extracts of both cockroach species on an anion-exchange medium results in the elution of three peaks with phosphorylase activity. According to their AMP dependency these activity peaks are designated as phosphorylase b (inactive without AMP), phosphorylase ab (active without AMP, but several times stimulated with AMP) and phosphorylase a (active without AMP). It is shown chromatographically that incubating crude extracts of fat bodies from both cockroaches, under conditions where the phosphorylase kinase is active, results in all phosphorylase b being converted to the ab- or a-form, whereas under conditions where the phosphorylase phosphatase is active all phophorylase a is converted to the ab- or b-form. Endogenous phosphorylase kinase of N. cinerea crude fat body extract can convert vertebrate phosphorylase b into the a-form, and, conversely, vertebrate muscle phosphorylase kinase and phosphorylase phosphatase, respectively, are able to convert partially purified N. cinerea phosphorylase ab or b and the ab- und a-form, respectively. In resting cockroaches most of the phosphorylase activity residues in the b-form and only a small fraction (10%) in the a-form, whereas between 26% (N. cinerea) and 35% (P. americana) occurs in the ab-form. Injection of endogenous hypertrehalosaemic peptides into N. cinerae (the decapeptide Bld-HrTH) or P. americana (the two octapeptides Pea-CAH-I and II) causes interconversion of phosphorylase; after injection, mainly (60%) phosphorylase a is present, while 25% and 15% exists in the ab- und b-form, respectively. Purification of the three phosphorylase forms from N. cinerea is achieved by anion-exchange chromatography on DEAE-Sephacel followed by affinity chromatography on AMP-Sepharose. The final specific activities are 2.1, 6.9 and 27.2 U/mg protein for the a-, ab- und b-form. The molecular mass of the active molecules on gel filtration is between 173,000 and 177,000, and SDS gel electrophoresis reveals a subunit mass of 87,100, suggesting a homodimeric structure for all three forms. Kinetic studies show hyperbolic saturation curves for the substrates glycogen and Pi, respectively, with KM values of 0.021, 0.019 and 0.073% for glycogen and 8.3, 6.3 and 17.9 mM for Pi (a , ab- and b-form). Phosphorylase a exhibits a more or less hyperbolic response to AMP and needs 70 microM AMP for maximal stimulation.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1903949 TI - Duration of carbon dioxide absorption by soda lime at low rates of fresh gas flow. AB - STUDY OBJECTIVE: To determine the impact of a low fresh gas flow rate on the duration of carbon dioxide (CO2) absorption by soda lime. DESIGN: Nonclinical, experimental. SETTING: Experimental laboratory. METHODS: In vitro test with Sodasorb and a semiclosed breathing circle ventilating a test lung with a CO2 inflow of 250 ml per minute. Fresh gas flow rates of 0.25, 0.5, 1, 2, and 4 L/min were studied. MEASUREMENTS AND MAIN RESULTS: CO2 was measured at the breathing circuit test lung interface with a mainstream capnometer. Duration of CO2 absorption was determined as the time for the inspired CO2 tension (PICO2) to increase from 0 mm to 7 mm of mercury. The times of this interval were recorded four times for each fresh gas flow rate and compared by analysis of variance; p less than 0.05 was considered significant. Time to soda lime failure was significantly longer at 2 L/min than at 1 L/min fresh gas flow and at 1 L/min than at 0.25 L/min fresh gas flow. CONCLUSION: Because soda lime color indicators are unreliable, when a semiclosed breathing circle is used at a low rate of fresh gas flow without CO2 monitoring, the CO2 absorbent must be replaced more frequently. PMID- 1903950 TI - Differential expression of neurofilament triplet proteins in carcinoid tumours: an immunohistochemical study. AB - Neurofilaments (NFs) are specific intermediate filaments to neural cells. Mammalian NFs are protein triplets composed of three major subunits with respective molecular weights of approximately 70, 150 and 200 kD. Using an immunohistochemical method, 13 carcinoid tumours from different sites were examined for the presence of these three subunits by means of monospecific antisera. All tumours contained cells that were positive for the 70 Kd subunit; nine cases contained cells immunoreactive for the 150 Kd subunit and only three of them for the 200 kD subunit. The results indicate that the 70 kD subunit is a good overall marker of carcinoid tumours. The 150 and 200 kD subunits are more likely to be absent in carcinoids, both typical and atypical. PMID- 1903953 TI - HIV transmission in India. PMID- 1903951 TI - Phase II clinical and endocrine study of Anandron (RU-23908) in advanced post menopausal breast cancer. PMID- 1903952 TI - The danger of studying human chorionic gonadotrophin action or expression in animal models. PMID- 1903954 TI - Professional conduct. Breaking the code. Interview by Jean Gray. PMID- 1903955 TI - Hospital security. Safe as houses. PMID- 1903956 TI - The Clay column. PMID- 1903957 TI - No-fault compensation. PMID- 1903958 TI - Victims of the war zone. PMID- 1903959 TI - Standardisation of wound care. AB - The bewildering array of wound care products on the market can serve to confuse rather than inform nurses working in clinical areas, and can lead to inconsistent approaches to wound management. Vicki Turner describes how she devised a wound care protocol in the form of a flowchart for her surgical orthopaedic ward, which aimed to standardise nurses' approaches to management and encourage a comprehensive problem-solving philosophy. Based on research findings, the guide has proved clinically successful and has also acted as an educational tool for student and junior nurses. PMID- 1903960 TI - The need to know. PMID- 1903961 TI - Depression and changing responses. AB - A therapeutic tool which assists in identifying the client's experience of depression would offer many virtues, particularly if that tool helped to break the experience down into more manageable elements for both client and therapist. In this article, Nicholas Holdsworth and Gordon Moore describe how it is possible to translate the results of the Beck Depression Inventory and the Coping Responses Questionnaire into complementary bar graphs which go some way to providing a baseline for therapeutic progress. PMID- 1903962 TI - Hospital management. The reflective practitioner. AB - Ian Campbell's paper, originally delivered at a conference on the development of 'The reflective practitioner' while he was Unit General Manager of Sunderland Royal Infirmary, describes the liaison between general and nurse managers in the hospital. Management must give a hospital organisation direction and must set the parameters of corporate and individual performance, but it must also be responsive to the feedback received from practising clinicians. The key concept is quality of service, and in this managers and practitioners can work together towards a common goal. PMID- 1903963 TI - Points of view. PMID- 1903964 TI - Belittle leaders. PMID- 1903966 TI - Sanity in a sick society. PMID- 1903965 TI - Christine Brown (1924-1990). PMID- 1903967 TI - Crisis in the Gulf. Drawing up the action plans. PMID- 1903968 TI - The return of casualties. PMID- 1903969 TI - Crisis in the Gulf. Post traumatic stress disorder explained. PMID- 1903970 TI - Injuries from chemical weapons. PMID- 1903971 TI - Care of the burns patient. PMID- 1903972 TI - Coping with a crisis. PMID- 1903973 TI - Audit commission: one of a kind. Interview by Jean Gray. PMID- 1903975 TI - North of England focus: batting for Yorkshire. Interview by Linda Thomas. PMID- 1903976 TI - Using Riehl's model in midwifery. PMID- 1903977 TI - Assessment of bone marrow donors. PMID- 1903978 TI - Developing nurses into managers. PMID- 1903974 TI - Children's painting competition: positive images. PMID- 1903979 TI - Psychiatric nursing: using behavioural psychotherapy skills. PMID- 1903980 TI - District nurses should teach patients post-discharge skills before they go into hospital. PMID- 1903981 TI - Cardiology update. Radiation protection. PMID- 1903982 TI - Cardiology update. Valvular surgery. PMID- 1903983 TI - Cardiology update. Food for a healthy heart. PMID- 1903984 TI - Cardiology update. Defibrillation. PMID- 1903985 TI - Cardiology update. Managing myocardial infarction today. PMID- 1903986 TI - Oscillatory Ca2+ signaling and its cellular function. AB - It is well known that in the cells of many higher eukaryotic organisms Ca2+ ions are used as a signal messenger in the regulation of cellular functions. From recent studies with single cells it was suggested that the intracellular Ca2+ signal comprises repetitive and periodic Ca2+ spikes in a variety of cells. The mechanism by which intracellular Ca2+ oscillates and the biological significance of this oscillation are not well understood. It also remains to be determined how the Ca2+ signaling system sends a message into the cell, intermittently, to amplify the functional response. This review describes and integrates some recent views of oscillatory Ca2+ signaling. PMID- 1903988 TI - [Cost-benefit analysis. V. Interdisciplinary discussions in radiology. Large equipment in radiology--problems of site planning (meeting report)]. PMID- 1903989 TI - Immunohistochemical diagnosis of protozoan parasites in lesions of equine protozoal myeloencephalitis. PMID- 1903987 TI - Direct gene transfer and expression into rat heart in vivo. AB - We found previously that genes injected into skeletal muscle can be taken up by myofibers and expressed. In the present study we found that myocardial cells can also express a variety of reporter genes injected into myocardium as efficiently as skeletal myofibers, while the cells of several other tissues cannot. The inability of tissues other than striated muscle to express injected DNA is not due to technical difficulties of injection because injected DNA was detected in these other tissues by PCR analysis. These results suggest that skeletal and cardiac muscle cells have unique features such as T tubules that may play a critical role in DNA uptake. Expression in cardiac muscle was stable for only two weeks, possibly because of an immune response against the transfected cells. The ability to directly transfer genes into myocardial cells raises the possibility of gene therapy for both acquired and genetic heart diseases. PMID- 1903991 TI - Adherent lymphokine-activated killer cells suppress autologous human normal bone marrow progenitors. AB - We have generated a homogeneous population of recombinant interleukin-2 (rIL-2) stimulated effector cells termed adherent lymphokine-activated killer cells (A LAK) from peripheral blood mononuclear cells (PBMNC) of 14 normal individuals and tested the effect of A-LAK cells on autologous hematopoietic bone marrow (BM) progenitor growth. Enrichment of A-LAK from PBMNC depended on the propensity of A LAK precursors to adhere to plastic and proliferate in the presence of rIL-2. The resultant population had the morphologic appearance of large granular lymphocytes, and the majority of cells (73% +/- 4%) expressed the CD56+/CD3- phenotype associated with rIL-2-stimulated natural killer (NK) cells. The A-LAK population had potent lytic activity in chromium release assays against both NK sensitive (K562) and NK-resistant (Raji) targets. When BM mononuclear cells (BMMNC) were coincubated with autologous A-LAK and rIL-2 (1,000 U/mL) added at the start of culture, dose-dependent suppression of burst-forming unit-erythroid (BFU-E) and colony-forming unit mix (CFU-MIX) colony growth was observed at effector to target ratios (E:T) ranging from 0.25:1 to 5:1 (maximal suppression BFU-E = 85% +/- 6%; CFU-MIX = 95% +/- 3%). This suppression was rIL-2 dose dependent, and no suppression was seen in the absence of rIL-2. Depletion of BM monocytes and T lymphocytes did not alter A-LAK suppression of progenitors coincubated with A-LAK cells. Addition of polyclonal neutralizing antibodies against both interferon-gamma (IFN-gamma) and tumor necrosis facto alpha (TNF alpha) to the coincubation culture completely abrogated the suppressive effect of A-LAK on BFU-E and CFU-MIX colony growth while each neutralizing antibody used alone had intermediate effects. In contrast to coincubation studies, 36 hours of preincubation of A-LAK cells with autologous BM (E:T 2.2:1) and rIL-2 (1,000 U/mL) followed by plating of preincubated BM cells in hematopoietic progenitor culture produced significant suppression of day 14 BFU-E (47% +/- 5%), but spared the more primitive CFU-MIX (7% +/- 9%), suggesting a divergent effect of A-LAK cells on hematopoietic progenitors at different stages of differentiation. Addition of neutralizing antibodies against IFN-gamma and TNF-alpha in preincubation failed to abrogate the suppressive effect of A-LAK on BFU-E colony growth, suggesting that this suppression occurs by a different mechanism than that seen in coincubation studies. Previous studies have demonstrated that the A LAK population has cytotoxic and proliferative advantages over other killer cell populations.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1903990 TI - Evaluation of XP-1: a new medium to culture mycobacteria in smooth form. PMID- 1903992 TI - Direct gas chromatographic determination of carbaryl residues in honeybees (Apis mellifera L.) using a nitrogen-phosphorus detector with confirmation by formation of a chemical derivative. PMID- 1903993 TI - Polychlorinated biphenyls in auto parts and auto fluff. PMID- 1903994 TI - Comparison of nucleoside concentrations in blood of fish with and without tumors. PMID- 1903995 TI - Effect of aluminum and pH on the growth of Anacystis nidulans. PMID- 1903996 TI - Parental transfer of organic contaminants to young-of-the-year spottail shiners, Notropis hudsonius. PMID- 1903997 TI - Influence of oral contraceptives on body temperature. PMID- 1903998 TI - Assessment of tumour-infiltrating lymphocytes, regional lymph node lymphocytes and peripheral blood lymphocytes and their reaction to interferon-gamma in patients with renal carcinoma. AB - The immunological distribution of tumour-infiltrating lymphocytes (TIL), regional lymph node lymphocytes (RLNL) and peripheral blood lymphocytes (PBL) was evaluated by means of immunohistochemical staining using monoclonal antibodies of each subset of lymphocytes (stored in frozen sections) in a series of 22 patients with renal carcinoma. The immunological effect of IFN (interferon)-gamma on these immunocompetent cells was also investigated. The effect of IFN-gamma on TIL was an increase in CD3 (pan-T cells), especially an increase in CD8 (cytotoxic/suppressor-T cells). When examining these cells according to stage and grade, a marked increase in CD3 was found in low stage and low grade patients. With regard to RLNL, there was a tendency towards a decrease in CD3 and an increase in CD20 (B-cells) following the administration of IFN-gamma. No specific effect on stage and grade was observed apart from a reduction in T cell subset ratios in high grade patients. With regard to PBL, no specific trend was noted except for an increase in CD16 (NK cells) when IFN-gamma was administered. PMID- 1903999 TI - Bladder instillations of trisdine compared with catheter introducer for reduction of bacteriuria during intermittent catheterisation of patients with acute spinal cord trauma. AB - An open, prospective, randomised trial was conducted to compare the incidence of significant bacteriuria following 2 methods of intermittent urethral catheterisation in patients with acute spinal cord trauma. Twenty-two patients were catheterised with a Nelaton catheter and 50 ml of Trisdine were instilled into the bladder and left there immediately prior to withdrawal of the catheter. Fifteen patients were catheterised with a Nelaton catheter with a special introducer to improve asepsis (O'Neil catheter). The mean incidence of significant bacteriuria in males and females who received Trisdine bladder instillations was 0.58 and 0.48% per catheterisation respectively; in males and females catheterised with the O'Neil catheter it was 1.16 and 2.93% per catheterisation respectively. The instillation of Trisdine into the bladder after each passage of a catheter resulted in a significantly lower incidence of bacteriuria compared with that which resulted from the use of the O'Neil catheter. The former method is therefore to be preferred for aseptic intermittent urethral catheterisation in patients with acute spinal cord trauma. PMID- 1904000 TI - Life at all costs. PMID- 1904002 TI - Glycosyltransferase changes upon differentiation of CaCo-2 human colonic adenocarcinoma cells. AB - The spontaneous differentiation of CaCo-2 human colonic adenocarcinoma cells to enterocytes in culture is associated with a decrease in polylactosaminoglycans, particularly those attached to the lysosomal membrane glycoprotein h-lamp-1 (Youakim et al., Cancer Res., 49:6889-6895, 1989). To elucidate the biosynthetic mechanisms leading to these alterations we have compared glycosyltransferase activities that are involved in the synthesis of polylactosaminoglycans and of the N- and O-glycan structures that provide the framework for the attachment of these chains. Glycosyltransferase activities in cell homogenates obtained from undifferentiated and differentiated CaCo-2 cells were assayed by high pressure liquid chromatography separation of enzyme products. The beta-galactosidase activities and extremely high pyrophosphatase activities in differentiated cells were effectively inhibited by 5 mM gamma-galactonolactone and 10 mM AMP, respectively. CaCo-2 cells contain most of the enzymes that are involved in N glycan branching [N-acetylglucosamine (GlcNAc) transferases I to V] with the exception of GlcNAc transferase VI. The levels of GlcNAc transferase I activities were comparable in undifferentiated and differentiated cells, but GlcNAc transferase II to V activities were significantly increased upon differentiation. The enzyme activities that are directly involved in the synthesis of linear polylactosaminoglycans (Gal beta 4GlcNAc beta 3- repeating units), blood group i UDP-GlcNAc:Gal beta-R beta 3-GlcNAc transferase and UDP-Gal:GlcNAc beta 4-Gal transferase, were found at similar levels in undifferentiated and differentiated CaCo-2 cells. Since GlcNAc transferase III activity is known to inhibit further branching and galactosylation, these results suggest that its increased activity in differentiated CaCo-2 cells may be partly responsible for the decreased synthesis of fucosylated polylactosaminoglycans. Differentiated cells showed a 2 fold increase in O-glycan core 2 UDP-GlcNAc:Gal beta 3GalNAc alpha-R [GlcNAc to N acetylgalactosamine (GalNAc)] beta 6-GlcNAc transferase activity. In contrast, O glycan core 1 UDP-Gal:GalNAc alpha-R beta 3-Gal transferase activity was found decreased. Several enzymes that are found in homogenates from normal human colonic tissue are absent or barely detectable in CaCo-2 cells. These include blood group I UDP-GlcNAc:GlcNAc beta 3Gal beta-R (GlcNAc to Gal) beta 6-GlcNAc transferase, O-glycan core 3 UDP-GlcNAc:GalNAc alpha-R beta 3 GlcNAc transferase and O-glycan core 4 UDP-GlcNAc:GlcNAc beta 3GalNAc-R (GlcNAc to GalNAc) beta 6 GlcNAc transferase. PMID- 1904003 TI - Infiltration and accumulation of precursor cytotoxic T-cells increase with time in progressively growing ocular tumors. AB - Precursors of cytotoxic T-cells (pTc) infiltrate P815 tumors growing progressively within the immunologically privileged anterior chamber (AC) of BALB/c mouse eyes, but directly cytotoxic T-cells cannot be detected in these eyes. To determine if the failure to reject these tumors is due to a relative inability of tumor-specific pTc to gain access to, or be retained by, the tumor containing eye, we have assayed through time the frequency of pTc in eyes that received P511 tumor cells in the AC or subconjunctival space (SC; a site where the tumors are rejected). P511 tumor cells, a hypoxanthine-amethopterin-thymine medium-sensitive derivative of P815 cells, were selected for these studies because P511 tumor cells can be eliminated from in vitro lymphocyte cultures containing hypoxanthine-amethopterin-thymine medium, permitting us to make accurate estimates of pTc frequencies. To ensure that P511 cells are similar biologically and immunologically to P815 tumor cells, we demonstrated that both P511 and P815 cells form progressively growing tumors when injected into the AC of BALB/c eyes and that recipients of both tumor cell lines develop DBA/2 specific anterior chamber-associated immune deviation. Using cell suspensions harvested from eyes of mice bearing AC or SC P511 tumors, we found that tumor specific pTc appeared first (day 8) in SC tumor-bearing eyes, compared to their appearance in AC tumor-bearing eyes (day 11). Thereafter, however, the number of pTc detected was significantly greater in eyes bearing progressively growing AC tumors than in SC tumor-injected eyes. The number and frequency of pTc we found in these eyes appeared to correlate directly with the size of the ocular tumor burden. We conclude that failure to reject P511 tumor from the AC can be ascribed neither to a quantitative deficiency in infiltrating tumor-specific pTc nor to an inability to retain pTc at the site. Our findings suggest that immune acceptance of allogeneic ocular tumor grafts may result from failure of infiltrating pTc to differentiate terminally in situ into cytotoxic effector cells. PMID- 1904001 TI - Modulation of murine radiation-induced fibrosarcoma-1 tumor metabolism and blood flow in situ via glucose and mannitol administration monitored by 31P and 2H nuclear magnetic resonance spectroscopy. AB - The hyperglycemia-induced in situ metabolism and blood flow changes produced in s.c. implanted murine radiation-induced fibrosarcoma-1 tumors, grown on the flanks of female C3H/HeJ mice, were examined with 31P and 2H nuclear magnetic resonance. Initial experiments verified a hyperglycemic tumor acidification similar to that reported earlier with a different substrain of mice, C3H/AnF (J.L. Evelhoch et al., Proc. Natl. Acad. Sci. USA, 81: 6496-6500, 1984). Changes in the tumor pH, phosphorus metabolites, and blood flow were then compared after administration of saline, glucose, or mannitol (a nonmetabolizable glucose analogue) using a mole-equivalent dose of the sugars (i.e., 0.8 mmol/20g mouse). Neither saline (n = 8) nor mannitol (n = 6) administration had any marked effect upon tumor pH, whereas glucose administration produced a mean maximum tumor pH reduction of 0.74 +/- 0.09 (SE; n = 9) during the 2.5 h post-glucose injection. No significant changes in high energy phosphate concentrations were observed during the same period after saline injection. After glucose injection, the [phosphocreatine] gradually decreased by 64% (P = 0.0001). After the initial 1 h post-glucose injection, the [inorganic phosphate] increased by 58% (P = 0.0001), and the [nucleoside triphosphates] decreased by 29% (P = 0.0001) during the following 1.5 h. After mannitol injection, while there was no change in [inorganic phosphate] over time (P = 0.37), the [phosphocreatine] decreased by 33% (P = 0.0001) and the [nucleoside triphosphates] decreased by 21% (P = 0.0015) within 20 min, then both the [phosphocreatine] and [nucleoside triphosphates] remained at constant levels during the following 2 h. In parallel experiments, the volumetric rate of tumor blood flow and perfusion was measured by 2H nuclear magnetic resonance monitoring of 2H2O washout kinetics (S-G. Kim and J. J. H. Ackerman, Cancer Res., 48: 3449-3453, 1988); tumor blood flow decreased by 80% (P = 0.0001, n = 11), 60% (P = 0.0031, n = 4), and 20% (P = 0.058, n = 10) at 2 h after glucose, mannitol, or saline injections, respectively. These results suggest that anaerobic glycolysis is a requirement for hyperglycemic tumor acidification. However, the decrease in tumor blood flow accompanying hyperglycemic acidification suggests that flow reduction also may be a contributing or a required cofactor for acidification via inhibition of lactic acid egress.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1904005 TI - Absence of methylthioadenosine phosphorylase in human gliomas. AB - All normal mammalian tissues contain methylthioadenosine phosphorylase, which plays a role in the recycling of purines and methionine consumed during polyamine synthesis. A complete deficiency of methylthioadenosine phosphorylase has been reported in some human leukemias and lymphomas and in a few solid tumors. The exact incidence of the enzyme deficiency among fresh human tumor specimens has been difficult to establish because the measurement of enzyme catalytic activity is laborious and requires carefully preserved specimens. We have generated two antibodies against methylthioadenosine phosphorylase and have used them to develop a simple immunoblot assay for the enzyme. Specifically, studies showed that all cells with catalytically active methylthioadenosine phosphorylase had a 32-kDa band that reacted with the anti-enzyme antibodies. In a reciprocal manner, all malignant cell lines that were naturally deficient in methylthioadenosine phosphorylase activity lacked detectable immunoreactive enzyme protein. The immunoassay was used to analyze human gliomas. Seventy-five % (9 of 12) of the gliomas were completely methylthioadenosine phosphorylase deficient. This common metabolic difference between most gliomas and all normal cells is a potential target for tumor-specific chemotherapy. PMID- 1904004 TI - Expression of HLA-A2 antigen in human melanoma cell lines and its role in T-cell recognition. AB - Previous studies have suggested that, in human melanoma, expression of HLA-A2 antigen is important for tumor cell recognition by autologous T-lymphocytes. Because of the recent demonstration that expression of HLA Class I antigens may be selectively lost in several human tumors, including melanoma, we derived pairs of tumor infiltrating lymphocytes (TIL) and melanoma cell lines from 4 human lymphocytic antigen (HLA)-A2+ patients with metastatic melanoma. We observed that, although all 4 TIL cultures expressed HLA-A2 antigen, only 2 melanoma cell lines did so. Melanoma cells derived from the other 2 patients showed neither surface expression of the HLA-A2 antigen nor presence of the corresponding mRNA. We also observed some correlation between loss of HLA-A2 expression and level of c-myc transcription. TIL derived from patients whose melanoma cell lines had normal expression of HLA-A2 had a CD8 phenotype and were capable of lysing autologous melanoma cells. Melanoma cell killing was CD3 and major histocompatibility complex Class I restricted in both cases, but HLA-A2 restricted in only one case. On the other hand, TIL derived from the 2 patients whose melanoma cell lines had lost expression of HLA-A2 had a predominant CD4 phenotype and virtually no cytotoxic activity. Preincubation of the HLA-A2 negative melanoma cell lines with alpha- or gamma-interferon did not induce the re-expression of the HLA-A2 antigen. In an attempt to restore HLA-A2 antigen expression in one of the melanoma cell lines that were HLA-A2 negative, we transfected these cells with the HLA-A2 gene subcloned in the pSV2-neo vector. Four transfected clones, with high levels of HLA-A2 antigen expression, were expanded and characterized. Proliferative and cytotoxic activities of TIL against the autologous transfected clones as well as the untransfected parental melanoma cell line were measured and compared. CD4+ TIL showed no difference in the proliferative response to autologous parental and HLA-A2 transfected clones. However, we observed selective recognition of the HLA-A2 expressing clones by autologous cultured peripheral blood lymphocytes (which contained CD8 cells) as well as allogeneic CD8+ TIL with a HLA-A2 restricted pattern of recognition. In contrast, virtually no cytotoxic activity was detected against either parental or HLA-A2 transfected clones. Overall, our data suggest that selective down regulation of HLA-A2 antigen expression in melanoma cells may represent one of the mechanisms by which tumor cells escape immunological recognition. PMID- 1904006 TI - No expansion of the pre-B and B-cell compartments in the bone marrow of patients with multiple myeloma. AB - We have recently demonstrated that the CD24 antigen density of bone marrow (BM) lymphoid cells discriminates between pre-B cells and mature B-cells. Using this new method, we evaluated the B-cell lineage in the BM and peripheral blood (PB) of 18 patients with multiple myeloma (MM). First, the percentage of pre-B cells was significantly reduced by 40% in the BM of patients with MM: 2.3% +/- 2.2% versus 5.7% +/- 2.8% of normal BM lymphoid cells (P less than 0.01). This finding was associated with a significant reduction (50%) of the percentage of mature B cells in both BM and PB, especially in patients with progressive disease (P less than 0.05). In contrast to what has been reported previously, we have not found any pre-B cells in the PB of these patients with MM. Secondly, BM pre-B and B cell patients with MM did not express any activation markers (CD23, CD25, or CD71 antigens) and no CD5+ B-cells were found in the BM unlike in PB (8% CD5+ B cells). Taken together, these data do not support the concept of a direct involvement (i.e, expansion or activation) of pre-B cells in MM without excluding the possibility of an early oncogenic event at the pre-B cell stage. Furthermore, our data emphasize this important reduction of the B-cell compartment (including that of pre-B cell) as a major cause of the humoral immunodeficiency in MM. PMID- 1904007 TI - The polarity of the dorsoventral axis in the Drosophila embryo is defined by an extracellular signal. AB - Twelve maternal effect loci are required for the production of Drosophila embryos with a correct dorsoventral axis. Analysis of mosaic females indicates that the expression of the genes nudel, pipe, and windbeutel is required in the somatic tissue, presumably in the follicle cells that surround the oocyte. Thus, information coming from outside the egg cell influences dorsoventral pattern formation during embryogenesis. In transplantation experiments, the perivitelline fluid from the compartment surrounding the embryo can restore dorsoventral pattern to embryos from females mutant for nudel, pipe, or windbeutel. The positioning of the transplanted pervitelline fluid also determines the polarity of the restored dorsoventral axis. We propose that the polarizing activity, normally present at the ventral side of the egg, is a ligand for the Toll receptor. Presumably, local activation of the Toll protein by the ligand initiates the formation of the nuclear concentration gradient of the dorsal protein, thereby determining dorsoventral pattern. PMID- 1904008 TI - Identification of cooperating oncogenes in E mu-myc transgenic mice by provirus tagging. AB - Mo-MLV infection of E mu-myc transgenic mice results in a dramatic acceleration of pre-B cell lymphomagenesis. We have used provirus tagging to identify genes that cooperate with the E mu-myc transgene in B cell transformation. Here we report on the identification of four loci, pim-1, bmi-1, pal-1, and bla-1, which are occupied by proviruses in 35%, 35%, 28%, and 14% of the tumors, respectively. bmi-1, pal-1, and bla-1 represent novel common proviral insertion sites. The bmi 1 gene encodes a 324 amino acid protein with a predominantly nuclear localization. bmi-1 is highly conserved in evolution and contains several motifs frequently found in transcriptional regulators, including a new putative zinc finger motif. No genes have yet been assigned to pal-1 and bla-1. The distribution of proviruses over the four common insertion sites suggests that provirus tagging can be used not only to identify the cooperating oncogenes but also to assign these genes to distinct complementation groups in tumorigenesis. PMID- 1904009 TI - Novel zinc finger gene implicated as myc collaborator by retrovirally accelerated lymphomagenesis in E mu-myc transgenic mice. AB - To search for genes that can collaborate with myc in lymphomagenesis, we exploited retroviral insertional mutagenesis in E mu-myc transgenic mice. Moloney murine leukemia virus accelerated development of B lymphoid tumors. Three quarters contained a provirus within the known pim-1 or pim-2 loci, new loci bmi 1 and emi-1, or combinations of these. bmi-1 insertions predominated, occurring in half the tumors, and resulted in elevated bmi-1 mRNA levels. Significantly, the bmi-1 gene, which is expressed in diverse normal cells, encodes a Cys/His metal-binding motif (C3HC4) that resembles those in several DNA-binding proteins and defines a new category of zinc finger gene. Thus, myc-induced lymphomagenesis can entail the concerted action of several genes, including the presumptive nuclear regulator bmi-1. PMID- 1904010 TI - Gamma-tubulin is present in Drosophila melanogaster and Homo sapiens and is associated with the centrosome. AB - The mipA gene of A. nidulans encodes a newly discovered member of the tubulin superfamily of proteins, gamma-tubulin. In A. nidulans, gamma-tubulin is essential for nuclear division and microtubule assembly and is associated with the spindle pole body, the fungal microtubule organizing center. By low stringency hybridizations we have cloned cDNAs from D. melanogaster and H. sapiens, the predicted products of which share more than 66% amino acid identity with A. nidulans gamma-tubulin. gamma-Tubulin-specific antibodies stained centrosomes of Drosophila, human, and mouse cell lines. Staining was most intense in prophase through metaphase when microtubule assembly from centrosomes was maximal. These results demonstrate that gamma-tubulin genes are present and expressed in humans and flies; they suggest that gamma-tubulin may be a universal component of microtubule organizing centers; and they are consistent with an earlier hypothesis that gamma-tubulin is a minus-end nucleator of microtubule assembly. PMID- 1904011 TI - The 102 kd cadherin-associated protein: similarity to vinculin and posttranscriptional regulation of expression. AB - The E-cadherin cell adhesion molecule is associated with cytoplasmic polypeptides, and this association is essential for its cell-binding function. Using isolated adherens junctions of the liver, we purified a 102 kd protein that can associate with E-cadherin (CAP102) and isolated cDNAs encoding this protein. Sequence analysis of the cDNAs revealed that this protein has a similarity to vinculin. L cells not expressing endogenous cadherin express the mRNA for CAP102 but have only a trace amount of CAP102 protein. Introducing exogenous E-cadherin into these cells, however, induced a high expression of CAP102 protein without affecting the amount of its mRNA, suggesting that there is a posttranscriptional regulatory mechanism for this molecule. The same effect was observed by introducing N- or P-cadherin into L cells. PMID- 1904014 TI - Coronary vasoconstriction induced by vasopressin. Production of myocardial ischemia in dogs by constriction of nondiseased small vessels. AB - BACKGROUND: We studied the effect of intracoronary administration of arginine-8 vasopressin on blood flow in nondiseased coronary arteries and determined whether this vasoconstriction was severe enough to produce ischemia in 30 dogs. METHODS AND RESULTS: In group 1 (n = 6), after vasopressin administration coronary blood flow was decreased by 41% (p less than 0.002) without changes in heart rate or aortic pressure, and left ventricular ejection fraction measured by radionuclide angiocardiography was decreased by 18% (p less than 0.0005). In group 2 (n = 6), ischemia was confirmed by measurement of transmural pH changes. Administration of vasopressin decreased subendocardial pH of the infused zone from 7.40 +/- 0.03 to 7.31 +/- 0.07 (p less than 0.01). The subendocardial pH of the zone not infused with vasopressin did not change. To overcome the intrinsic regulation of blood flow, operating primarily in small coronary arteries, we hypothesized that vasopressin must increase resistance primarily in large rather than small coronary arteries. After intracoronary infusion in group 3 (n = 6), however, most (94%) of the increase in resistance during vasopressin administration was explained by an increase of resistance in small coronary arteries. In group 4 (n = 9), vasopressin decreased coronary blood flow by 50% and decreased local shortening by 90% at a time when systemic hemodynamics were unchanged. Coronary constriction induced by vasopressin, or the recovery from it, also was not altered by cyclooxygenase blockade. CONCLUSIONS: Thus, vasopressin produces myocardial ischemia by constricting small, nondiseased coronary arteries severely enough to overcome the competition from normal coronary regulation, and this ischemic event is not mediated by prostaglandin products. PMID- 1904013 TI - Direct in vivo gene transfer into the coronary and peripheral vasculatures of the intact dog. AB - Gene therapy approaches have been suggested for the treatment of cardiovascular disease. Recently, direct transfer of the gene encoding beta-galactosidase into peripheral arteries of the pig has been demonstrated. To determine whether this approach is applicable to other arterial beds and to other species, we first evaluated the use of beta-galactosidase as a marker protein in the canine model. We demonstrate that variable but substantial endogenous beta-galactosidase-like activity is induced by manipulation of canine peripheral arteries, which precludes the use of this marker protein in evaluating the efficiency of gene transfer in this model. A marker gene encoding firefly luciferase was then evaluated, and background luciferase activity was found to be low in the dog even after arterial manipulation. Using the luciferase gene, we then demonstrated lipid-mediated gene transfer directly into both coronary and peripheral arteries of the intact dog. These results indicate the feasibility of in vivo gene transfer into coronary arteries and demonstrate the use of the luciferase marker protein in quantifying recombinant protein expression following gene transfer in canine models. This simple and effective method for direct in vivo gene transfer into coronary and peripheral arteries may be applicable to the localized production of therapeutically important proteins for the treatment of cardiovascular diseases. PMID- 1904012 TI - Fluosol-DA/carbogen with lonidamine or pentoxifylline as modulators of alkylating agents in the FSaIIC fibrosarcoma. AB - In an effort to increase the efficacy of several antineoplastic alkylating agents (CDDP, L-PAM, CTX, or BCNU), we examined the effect of the modulator Fluosol DA/carbogen in combination with a second modulator, either lonidamine or pentoxifylline, on the survival of FSaIIC tumor cells and of bone marrow CFU-GM from tumor-bearing C3H mice. Fluosol-DA/carbogen increased the tumor-cell killing activity of each alkylating agent by about 10 times. In contrast, lonidamine alone did not significantly increase the cytocidal activity of any of the alkylating agents tested. However, in combination with Fluosol-DA/carbogen, the use of lonidamine produced about a 100-fold increase in the tumor cell kill achieved with CDDP as compared with CDDP alone. No increase in tumor cell kill over that produced with the single modulator Fluosol-DA/carbogen was seen following the addition of lonidamine to the combination treatment with L-PAM, CTX, or BCNU. Unfortunately, although neither lonidamine nor Fluosol-DA/carbogen alone significantly increased alkylator toxicity to bone marrow CFU-GM, the combination of modulators increased the toxicity of each alkylating agent to bone marrow by about 10 times. Pentoxifylline caused an increase in alkylator activity against the FSaIIC fibrosarcoma only when used with BCNU; this effect was further augmented by the addition of Fluosol-DA/carbogen. The combination of modulators pentoxifylline plus Fluosol-DA/carbogen was more effective than Fluosol DA/carbogen alone only when the former was used with BCNU, whereas only minimal increases in tumor-cell killing activity were obtained with this modulator combination and CDDP, L-PAM, or CTX. Pentoxifylline increased the bone marrow CFU GM toxicity of L-PAM by about 10 times. The bone marrow CFU-GM toxicity was further increased by Fluosol-DA/carbogen, as was the toxicity of each of the other alkylating agents. Lonidamine plus Fluosol-DA/carbogen may be useful in increasing the therapeutic efficacy of CDDP, and the combination of pentoxifylline plus Fluosol-DA/carbogen might improve the antitumor activity of BCNU. PMID- 1904016 TI - Transient expression of c-fos during the development of the rat cerebral cortex. AB - The present study has explored with immunocytochemical methods the expression of the proto-oncogene c-fos during the pre- and postnatal development of the cerebral cortex of the rat. The immunostaining of the Fos protein follows a strikingly precise spatiotemporal pattern: it occurs uniquely within layer VIb of the developing cerebral cortex, and is transient, lasting only from embryonic day 20 until postnatal day 1. The expression of c-fos in layer VIb may be related to the dynamic changes that occur at this level during development. PMID- 1904015 TI - Intravenous nitroglycerin infusion inhibits cyclic blood flow responses caused by periodic platelet thrombus formation in stenosed canine coronary arteries. AB - BACKGROUND: Nitroglycerin and other clinically relevant organic nitrate derivatives have been shown to inhibit platelet aggregation in vitro. This antithrombotic effect of nitrates is potentiated by reduced thiol. To determine the potential relevance of this mechanism of action in vivo, we examined the effect of intravenous nitroglycerin infusion on periodic platelet thrombus formation in a canine model of coronary artery stenosis. METHODS AND RESULTS: We used a canine model of coronary artery stenosis associated with cyclic reductions in coronary blood flow that have been shown to depend on periodic platelet thrombus formation. We quantified the frequency of cycles per 40-minute observation period and monitored the effect of a continuous infusion of intravenous nitroglycerin on the cycle frequency. The administration of 10-15 micrograms/kg/min nitroglycerin reduced cyclic platelet thrombus formation significantly and did so without a significant change in coronary artery blood flow. Pretreatment with the reduced thiol, N-acetylcysteine (100 mg/kg during 30 minutes), led to inhibition of cyclic platelet thrombus formation by intravenous nitroglycerin at doses that alone had no such effect (5 micrograms/kg/min). CONCLUSION: These data suggest that one mechanism by which intravenous nitroglycerin improves ischemia in acute coronary artery disease syndromes may be by inhibition of platelet thrombus formation and may highlight the potential importance of reduced thiol in this mechanism. PMID- 1904018 TI - Why spend the money? Justification of laboratory information systems. AB - Laboratory information systems (LISs) represent a major budget expense. Justification of their acquisition can be conducted through several methods. Work flow, work load, LIS experience, organization, and markets vary among laboratories; thus, each laboratory faces different challenges in determining if LIS acquisition can be justified on a sound business basis. PMID- 1904017 TI - Relative roles of prostaglandins and leukotrienes in canine hypoxic pulmonary vasoconstriction. AB - We indirectly examined the role of prostaglandins and leukotrienes in modulation of hypoxic pulmonary vasoconstriction. We used a cyclo-oxygenase inhibitor (indomethacin) and a lipoxygenase inhibitor (diethylcarbamazine) in an in-situ canine lung lobe preparation. We measured total resistance in two control groups ventilated with either 35% O2 or 3% O2 (groups CC and HC respectively). Two additional groups treated with indomethacin (groups CI and HI), and two groups treated with the combination of indomethacin and diethylcarbamazine (groups CID and HID), were also ventilated with either 35% O2 or 3% O2 respectively. Total resistance was significantly greater in hypoxic groups compared with their respective control oxygen groups. Total resistance was greatest in group HI (0.288 +/- 0.103 cm H2O.ml-1 min-1), intermediate in group HID (0.153 +/- 0.016 cm H2O.ml-1 min-1) and lowest in group HC (0.066 +/- 0.017 cm H2O.ml-1 min-1). We concluded that cyclo-oxygenase blockade augments hypoxic pulmonary vasoconstriction by decreasing production of a vasodilating prostaglandin. Hypoxia also increases production of a vasoconstricting leukotriene in the presence of cyclo-oxygenase blockade with indomethacin. PMID- 1904019 TI - Association between contraceptive method accepted and perception of information received: a comparison of Norplant and IUD acceptors. AB - In the present study Norplant(R) and IUD acceptors who attended the same counseling sessions have been compared on their perception of the information received at the family planning clinic. The study covered 100 acceptors of each method quota matched by parity and years of schooling. Data were obtained through home interviews. The two groups presented no significant differences when selected socio-demographic characteristics were analyzed. Norplant users recalled more information on this method than did IUD acceptors, and the content of what they remembered was different. This included concepts as important as risk of pregnancy, menstrual and health effects, and method of removal. The results suggest that the intrinsic qualities of the new method and the presence of a group of women motivated to use one with its general characteristics, are not sufficient conditions for its acceptance. PMID- 1904020 TI - The efficacy and acceptability of a low-dose levonorgestrel intravaginal ring for contraception in a UK cohort. AB - The efficacy and acceptability of a levonorgestrel-releasing intravaginal ring (IVR) for contraception was assessed in a British cohort studied as part of a multicentre, multinational clinical trial performed under the auspices of the World Health Organisation. One-hundred-and-fifty women took part in the study in two UK centres and completed 1417.5 months of method use. Fifty-nine women discontinued use of the IVR before the end of one year giving an overall discontinuation rate of 39.9 per 100 woman-years. The discontinuation for pregnancy with the ring in situ, was 3.0 per 100 woman-years (life table analysis). Menstrual disturbance, vaginal problems and involuntary expulsion resulted in discontinuation rates of 8.9, 8.4 and 1.6 per 100 woman-years, respectively. This method is an acceptable and effective method of contraception for women. PMID- 1904021 TI - Experience with a potent LH-RH agonist, buserelin, alone and in combination with testosterone for antispermatogenic activity, reversibility and toxicity in langur monkey. AB - Chronic intermittent treatment of LH-RH superagonist Buserelin alone or in combination with testosterone enanthate were given to adult male langurs for 90 days to evaluate antispermatogenic activity of alone and combination therapy, maintenance of normal androgenicity, possible toxic effects of agonist treatment, related side effects of testosterone supplementation and complete reversibility of the procedure. A gradual decrease in sperm count was recorded in both treatment groups, along with reduced motility and vitality of the spermatozoa. In the combination group, oligospermia was achieved in 4 out of 5 animals, whereas, only 2 animals became oligospermic in the agonist alone group. Significant decrease in serum testosterone levels along with impaired libido and other testosterone withdrawal symptoms were observed in the Buserelin alone group, conversely normal testosterone levels and libido were observed in the combination group. An elevation in haematological variables and serum total protein concomitant with a slight gain in body weight of the animals were recorded in the combination group; these changes were not encountered in the agonist alone group. Reversibility of all the altered parameters to control range was observed in both treatment groups following 75 to 90 days of treatment withdrawal. PMID- 1904022 TI - Ultrastructural analysis of polytene chromatin of Drosophila melanogaster reveals clusters of tightly linked co-expressed genes. AB - Patterns of gene activity on individual chromatids of polytene chromosomes of Drosophila melanogaster white prepupae were ultrastructurally characterized by electron microscopy. The band-interband structure of salivary gland polytene chromosomes is lost when they are dispersed in a low ionic strength detergent solution. Morphologically similar, active genes in close proximity to one another were seen in dispersed white prepupal chromatin. The arrays of genes almost certainly represent sister copies of the same locus. Although lateral register between gene copies on multiple strands was not maintained, analysis of sister transcriptional units of unknown identity was achieved at the periphery of the chromatin arrays. Juxtaposed genes with divergent transcriptional polarity were prevalent. The morphology, size and transcriptional polarity of multiple copies of short, tandemly organized, RNA polymerase dense, co-expressed gene clusters is reported. One highly transcriptionally active region, designated the white prepupal locus (WPP locus), composed of a co-expressed tandem cluster of ten genes within an approximately 50 kb region was analyzed on six separate chromatids. The transcriptional map suggests that the pattern of gene activity for at least one gene within the cluster may not be identical on all homologous strands. The survey of active polytene genes provides ultrastructural correlation with previous molecular data that demonstrate tight linkage of certain developmentally co-regulated Drosophila genes. Our findings are discussed in relation to Drosophila gene organization, clustering, and regulation of gene expression. PMID- 1904024 TI - Identification of Lys116 as the target of N-ethylmaleimide inactivation of ferredoxin:NADP+ oxidoreductase. AB - Oxidized ferredoxin:NADP+ oxidoreductase (FNR) was slowly and irreversibly inactivated by N-ethylmaleimide. Complete protection against inactivation was afforded by saturating concentrations of NADP+. In the presence of NADPH, a rapid inhibition of the enzyme ensued; however, this inhibition was found to be reversible. In the tryptic map of the flavoprotein, modified with N-ethyl[2,3 14C]maleimide in oxidizing conditions, a unique radioactive peptide was found. Its sequence comprised residues 110-117 of the enzyme: Lys116 was shown to be the residue alkylated by N-ethylmaleimide. It is noteworthy that the same residue of FNR was found to be modified by 5-dimethylaminoaphthalene-1-sulfonyl(dansyl) chloride at the putative NADP(H)-binding site [Cidaria, D., Biondi, P. A., Zanetti, G. & Ronchi, S. (1985) Eur. J. Biochem. 146, 295-299]. Furthermore, the data reported here demonstrate that the sulfhydryl groups of FNR are not involved in enzyme inactivation by N-ethylmaleimide. PMID- 1904023 TI - Sequential measurements of bone lead content by L X-ray fluorescence in CaNa2EDTA treated lead-toxic children. AB - With the development of L X-ray fluorescence (LXRF) to measure cortical bone lead directly, safely, rapidly, and noninvasively, the present study was undertaken to a) evaluate LXRF as a possible replacement for the CaNa2EDTA test; b) quantify lead in tibial cortical bones of mildly to moderately lead-toxic children before treatment; and c) quantify lead in tibial cortical bones of lead-toxic children sequentially following one to two courses of chelation therapy. The clinical research design was based upon a longitudinal assessment of 59 untreated lead toxic children. At enrollment, if the blood lead (PbB) was 25 to 55 micrograms/dL and the erythrocyte protoporphyrin (EP) concentration was greater than or equal to 35 micrograms/dL, LXRF measurement of tibial bone lead was carried out. One day later, each child underwent a CaNa2EDTA provocative test. If this test was positive, lead-toxic children were admitted to the hospital for 5 days of CaNa2EDTA therapy. These tests were repeated 6 weeks and 6 months after enrollment. Abatement of lead paint hazards was achieved in most apartments by the time of initial hospital discharge. The LXRF instrument consists of a low energy X-ray generator with a silver anode, a lithium-doped silicon detector, a polarizer of incident photons, and a multichannel X-ray analyzer. Partially polarized photons are directed at the subcutaneous, medial mid-tibial cortical bone. The LXRF spectrum, measured 90 degrees from the incident beam, reveals a peak in the 10.5 KeV region, which represents the lead L alpha line.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1904025 TI - Metal affinity precipitation of proteins carrying genetically attached polyhistidine affinity tails. AB - In this study, galactose dehydrogenase (EC 1.1.1.48) was chosen as a prototype target protein to investigate the capability of metal affinity precipitation to facilitate the purification of genetically engineered proteins. A DNA fragment encoding five histidine residues was fused to the 3'-terminal end of the galactose dehydrogenase gene from Pseudomonas fluorescens and thereafter expressed in Escherichia coli. The additional five histidines functioned as an affinity tail and the modified enzyme could be purified using metal affinity precipitation when the metal-chelate complex with ethylene glycol-bis-(beta aminoethyl ether) N,N,N',N'-tetra-acetic acid, EGTA(Zn)2, was added to the protein solution. The affinity tail could also be applied for the purification of the fusion protein utilising immobilised metal affinity chromatography. After purification, the pentahistidine affinity tail could be removed enzymatically by carboxypeptidase A. Furthermore, growth rate experiments demonstrated that the expression of the metal-binding affinity tail in E. coli cells enhanced the tolerance to zinc ions when added to the growth medium. PMID- 1904026 TI - Characterization of a novel type of chain-terminator Gal beta 1-6Gal beta 1 4)GlcNAc in an oligosaccharide related to N-glycosylated protein glycans isolated from GM1 the urine of patients with gangliosidosis. AB - Two new oligosaccharides were isolated from the urine of a patient with GM1 gangliosidosis. Final purification of the oligosaccharides was accomplished by capillary supercritical fluid chromatography. Structural analysis was by chemical analysis, chemical-ionization mass spectrometry and 400-MHz 1H-NMR spectroscopy, leading to two primary structures. The first is derived from a classical triantennary N-acetyllactosamine-type glycan: Gal beta 1-4GlcNAc beta 1-4(Gal beta 1-4GlcNAc beta 1-2)Man alpha 1-3Man beta 1-4GlcNAc. The second is unusual with a terminal disaccharide Gal beta 1-6Gal, which had not yet been described for glycans of the N-acetyllactosamine type: Gal beta 1-6Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6Man beta 1-4GlcNAc. PMID- 1904027 TI - N-linked glycosylation affects the processing of mouse submaxillary gland prorenin in transfected AtT20 cells. AB - Most mouse inbred strains carry two renin genes, Ren-1 and Ren-2, Renin-2, the product of the Ren-2 gene, is highly expressed in the submaxillary gland. It is a renin isoenzyme 96% similar to kidney renin-1, but unglycosylated. In order to investigate if glycosylation of prorenin affects its processing and/or secretion we have introduced two potential N-linked glycosylation sites into preprorenin-2 cDNA using site-directed mutagenesis. Expression plasmids were derived from wild type and mutant renin-2 cDNA and were transfected into AtT20 cells. Both transfected cells, expressing glycosylated or unglycosylated forms, secreted prorenin and renin by the constitutive and regulated pathways, respectively. Prorenin was correctly processed to active renin but the second maturation site was not cleaved in AtT20 cells. The comparison of glycosylated and unglycosylated renin expression showed a diminished secretion of glycosylated active renin. Prevention of glycosylation with tunicamycin resulted in an improved secretion of active renin. Moreover, the efficiency of the trypsin activation in vitro was reduced for glycosylated prorenin and it was restored when the activation was performed on mutant renin secreted from tunicamycin-treated cells. It is proposed that the bulky carbohydrates attached to prorenin constitute a steric hindrance to proteolysis by maturation enzymes. PMID- 1904028 TI - Value of electrocardiographic scoring systems for the assessment of thrombolytic therapy in acute myocardial infarction. The European Cooperative Study Group for Recombinant Tissue Type Plasminogen Activator. AB - The value of the Selvester and Cardiac Infarction Injury Scores was assessed in a randomized, placebo-controlled study of intravenous recombinant tissue plasminogen activator (rt-PA) in 721 patients with acute myocardial infarction. Electrocardiograms (ECG) obtained at admission, 6 h and 10 to 22 days after the start of therapy were analysed. Patients with prior myocardial infarction or QRS duration greater than or equal to 120 ms were excluded, leaving 322 in the rt-PA group and 333 in the placebo group. Cumulative 72-h release of alpha hydroxybutyrate dehydrogenase (HBDH) and global ejection fraction derived from angiography and nuclear scintigraphy were used as independent measures of infarct size. Predischarge results demonstrated a net benefit of rt-PA therapy, with the Selvester Score 11% lower (P less than 0.01) and the Cardiac Infarction Injury Score 5.4% lower (P = NS) in the rt-PA than the control group. Total enzyme release was reduced by 19.2% (P less than 0.001) in the rt-PA group. In patients with inferior infarction, neither enzyme release (r = 0.30 to 0.40) nor ejection fraction (r = 0.22 to 0.31) correlated well with the ECG indices of infarct size. In anterior infarction, the correlations were better, especially between the Selvester Score and enzyme release (r = 0.40 to 0.48) as well as ejection fraction (r = -0.48 to -0.67). It is concluded that ECG scoring systems, especially the Selvester Score, although imperfect are useful to assess thrombolytic therapy in clinical trials. However, their value for the management and assessment of thrombolytic therapy in individual patients is still limited. PMID- 1904029 TI - Rebound myocardial ischaemia following abrupt interruption of intravenous nitroglycerin infusion in patients with unstable angina at rest. AB - Isolated observations prompted a prospective study of the possible occurrence of myocardial ischaemia following abrupt discontinuation of intravenous infusion of nitroglycerin in 46 consecutive patients with unstable angina. In 26 (55%, group 1), but not the remainder (45%, group 2), cessation of nitroglycerin produced in 10.3 +/- 5.8 (mean +/- SD) minutes ECG changes comparable with those of spontaneous angina without significant changes in heart rate and blood pressure. Reproducible results were observed in 18/20 patients in whom the test was repeated. In four patients with two positive tests, a third test failed to elicit ischaemia 15 min after sublingual administration of 5 mg isosorbide dinitrate. An ergonovine test performed in four other patients with a positive test produced similar ECG changes. Thus, acute interruption of intravenous nitroglycerin infusion in patients with unstable angina is often associated with acute myocardial ischaemia. The lack of preceding changes in heart rate and blood pressure and the similarities with the spontaneous episodes and with those produced by ergonovine, strongly suggest a rebound coronary vasoconstrictive phenomenon as the underlying mechanism. PMID- 1904030 TI - Unexpected side-effects of inhaled steroids: a case report. AB - An asthmatic child is presented who developed a cushingoid appearance with evidence of adrenal suppression and growth impairment while on low dose inhaled topical steroids. When the inhaled steroids were replaced by inhaled sodium cromoglycate his adrenal function recovered while his appearance and growth returned to normal. This report indicates that there are some children who are at risk of developing side-effects on doses of inhaled topical steroids normally considered to be entirely safe. PMID- 1904031 TI - Delayed splenic development or transient asplenia? PMID- 1904032 TI - Comparison of isobutyl nitrate and isobutyl nitrite: tolerance and cross tolerance to glyceryl trinitrate. AB - This study includes the first systematic comparison of an organic nitrate with the corresponding organic nitrite-isobutyl nitrate and isobutyl nitrite. The spasmolytic activity of the nitrite on isolated rabbit aortic strips was stronger, more rapid in onset, but less stable than the activity of the nitrate. In vitro tolerance to glyceryl trinitrate and isobutyl nitrite greatly weakened the activity of isobutyl nitrate, respectively, but had much less effect on isobutyl nitrite. Possible reasons for these differences are discussed. PMID- 1904033 TI - Methoctramine, a cardioselective antagonist: muscarinic receptor mediating prostaglandin synthesis in isolated rabbit heart. AB - The antimuscarinic properties of the methoctramine with high selectivity for cardiac muscarinic M2 receptors were investigated on cholinergically induced changes in prostaglandin (PG) synthesis and mechanical function in the isolated perfused rabbit heart. Acetylcholine (ACh)- and arecaidine propargyl ester (APE) induced increases in PG synthesis were significantly attenuated by methoctramine in a concentration-dependent manner. Methoctramine at a low concentration of 0.1 microM potentiated ACh-induced PG synthesis, which was blocked by simultaneous infusion of hexahydro-sila-difenidol (HHSiD), a M3 receptor antagonist. Methoctramine produced an additive effect with HHSiD in diminishing the ACh- or APE-induced PG synthesis. Methoctramine displayed a potent antagonistic activity at M2 receptors that mediate the decrease in heart rate and increase in coronary perfusion pressure in isolated perfused rabbit heart. Methoctramine also minimized ACh- and APE-induced decrease in developed tension. In contrast, at 0.1 0.75 microM it exhibited no antagonistic activity at vascular muscarinic receptors (M3) mediating vasodilation in response to ACh or APE. These data suggest that methoctramine has a high affinity for cardiac M2 receptors mediating increases in PG output and coronary perfusion pressure as well as decrease in heart rate and developed tension and has a low affinity for M3 receptors mediating coronary vasodilator response. PMID- 1904034 TI - [A case of two successful deliveries by a woman with Kallmann syndrome and NIDDM]. AB - A 37 year-old female with Kallmann syndrome and NIDDM who had two successful deliveries is reported. She had experienced no menstruation until she had treatment with gestagen in her early twenties. She had withdrawal bleeding only once. At the age of 25, she consulted her family doctor, complaining of amenorrhea. Estrogen progesterone cyclic therapy caused withdrawal bleeding, and clomiphene citrate failed to induce apparent ovulation. In January 1978, 150 IU of hMG was administered daily for 9 days, and then 3000 IU of hCG daily for the following 2 days. This therapy induced pregnancy, which failed spontaneously on June 4th. A year later, in January 1979, 150 IU of hMG was again administered daily for 7 days followed by 6000 IU of hCG for 3 days. This therapy again induced pregnancy. On September 27th, 1979, she delivered a girl vaginally, weighing 3830 g. After this delivery, she experienced no menstruation. In June 1985, she consulted her family doctor again, and she was diagnosed as being pregnant. Since her fasting blood glucose was 145 mg/dl, she was admitted to Kosei Hospital to control her blood glucose. On October 15th, she delivered a girl weighing 2600 g. On June 13th, 1989, she was referred to Kosei Hospital by her family doctor to achieve an accurate control of her blood glucose. During this admission, she was diagnosed as having Kallmann syndrome because of congenital anosmia and hypogonadotropic hypogonadism without any abnormal morphological changes. Vitamin B1 infusion test was negative.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1904035 TI - Expression of the guanine nucleotide-binding protein Go correlates with the state of neural competence in the amphibian embryo. AB - The nucleotide-binding protein Go is a transducing molecule closely associated with neural structures in vertebrates. Because of the potential importance of molecules of this type during the first step of neurogenesis, we have investigated the kinetics of expression of Go in the amphibian (Pleurodeles waltl) embryo, focusing our attention on the stages corresponding to the acquisition of neural competence by presumptive ectoderm and to the process of neural induction. Using affinity-purified IgGs directed against the alpha subunit of Go, Go-like immunoreaction (GoLI) is first detected at the midblastula stage in some animal cap (future ectodermal) cells just before they have attained competence to be neuralized. At the early gastrula stage, GoLI is almost exclusively expressed by neural-competent tissue as a whole, with no obvious difference between the dorsal (prospective neural) and the ventral (prospective epidermal) ectoderm. The expression of GoLI is therefore related to the state of competence of the tissue rather than to its fate. At the early neurula stage, immediately following neural induction, the expression of GoLI persists essentially in that part of ectoderm that has been diverted from epidermal differentiation towards the neural pathway; in the ventral ectoderm, as neural competence is lost GoLI disappears. Furthermore, in the neurectoderm, only approximately 70% of the cells conserve GoLI, demonstrating that immediately following neural induction the population of neurectodermal cells is not homogeneous. PMID- 1904036 TI - Translational discrimination of ribosomal protein mRNAs in the early Drosophila embryo. AB - Most Drosophila mRNAs are actively translated in the early embryo, with the exception of the poorly translated ribosomal protein (r-protein) mRNAs. Two possible mechanisms for this translational discrimination were tested: (1) Translation of r-protein mRNAs is discriminated against by the limited activity of translational initiation factors in the early embryo and (2) translation of r protein mRNAs is repressed by trans-acting factors that reversibly bind these mRNAs. Exogenously provided initiation factors promoted partial recruitment of r protein mRNAs into polysomes, suggesting that modulation of initiation factor activity may play a role in the translational discrimination of r-protein mRNAs during embryogenesis. No evidence for involvement of reversibly binding trans acting factors was obtained, although there are limitations in the interpretation of the latter experiments. PMID- 1904037 TI - Long-term intermittent administration of interferon-alpha in patients with chronic non-A, non-B hepatitis. AB - IFN-alpha was administered intermittently over a 6 month period in 39 patients with chronic non-A, non-B hepatitis confirmed by peritoneoscopy and liver biopsy. Three million units of IFN-alpha were administered 3 times a week for the first 6 months then twice, then once a week. In 26 patients (67%), GPT decreased and remained within the normal range during the course of administration, and in 9 patients (23%) GPT remained normal for over 6 months after the discontinuation of IFN-alpha. There was no significant difference of efficacy among 3 groups liver histology groups (CPH, CAH-2A, and CAH-2B), but GPT decreased significantly in patients with sporadic hepatitis compared to patients with a history of blood transfusion. Furthermore, GPT decreased significantly in patients with a history of a blood transfusion within the preceding 2 years compared to patients with a history of a blood transfusion over 7 years ago. GPT increased markedly after an early tapering to 2 doses weekly, but it did not increase after a 6 month administration. In conclusion, the long-term administration of 300 million unit IFN-alpha, 3 times weekly for 6 months, about 2.5 hundred million units in total, is thought to be an effective way to control chronic NANB hepatitis. PMID- 1904038 TI - [Comparison of conventional radium and high dose rate afterloading brachytherapy in cervix cancer]. AB - The combination of intracavitary and external-beam radiation is the treatment of choice in advanced cervical cancer. Low-dose regimens using radium were widely abandoned in favour of high-dose-rate afterloading systems. We compared in this retrospective analysis of 550 patients the 2 different treatment modalities. We could observe neither in overall survival, nor in the incidence of side effects, any significant difference. Although the change from low- to high-dose-rate radiation therapy was not accompanied by a benefit in survival, the latter modality displayed several advantages e.g. a reduced exposure of personnel to radiation and shorter duration of confinement to bed. Patient survival rate was dependent mainly on parameters of tumour burden (FIGO stage), i.v. pyelogram or CT scan of paraaortic lymph nodes. On the other hand, neither the histological classification as epidermoid or adenocarcinoma nor the WHO grading, were useful predictors of patient outcome. PMID- 1904040 TI - [Androgens and other hormones in buserelin therapy]. AB - 23 women of reproductive age were treated with Buserelin nose-spray for endometriosis, which had been diagnosed by laparoscopic and bioptic methods. The treatment period was 6 months. Various hormones in serum were determined after 2, 4, 8, 12, 16, 20 and 24 weeks during treatment. LH, E2, prolactin, progesterone, and testosterone concentrations were significantly decreased under Buserelin therapy, whereas there was only a slight decrease in FSH, free testosterone and androstendion. No changes were observed in the concentrations of DHEAS and SHEBG. Buserelin had no androgenic effect. There was a significant decrease of endometriosis as judged by the implantation score. PMID- 1904039 TI - [Contraception by cyclic treatment with buserelin and progesterone]. AB - Hormonal contraception with a combination of a GnRH-agonist (Buserelin) and progesterone was achieved in 47 high risk patients in 547 cycles. In these patients, oral contraceptives were contraindicated because of severe cardiovascular diseases, thromboembolic complications, benign liver tumours, advanced diabetes, terminal kidney insufficiency and severe migraine. Buserelin was administered intranasally in one daily dose of 300-400 micrograms from the 1st day to the 21st day, one dose of 100 mg of Progesterone was given intravaginally daily from the 12th day to the 21st day. Under these conditions, average E2 concentrations were found in the range of 50-60 pg/ml. The discontinuation of progesterone replacement resulted in withdrawal bleeding. Cycle control was acceptable. In 4 cases, this contraceptive regimen had to be discontinued because of side effects or paradox reactions. One patient conceived. In conclusion, GnRH-analogues in a moderate dose can be used to inhibit ovulation without inhibiting follicular maturation and adequate oestrogen production. This costly regimen of contraception requires strict indication and careful monitoring. PMID- 1904041 TI - Cloning of nitrogenase structural genes from the obligate methanotroph Methylococcus capsulatus (Bath). AB - Southern hybridization techniques were used to examine the DNA homologies between the three nitrogenase structural genes nifH, nifD and nifK of Klebsiella pneumoniae and DNA from the obligate methane oxidizing bacterium Methylococcus capsulatus (Bath). The high degree of homology between methanotroph DNA sequences and the Klebsiella nifH and nifD genes was used to isolate and clone the corresponding Methylococcus nifH and nifD genes. Subsequent restriction analysis revealed that all three nif structural genes were contiguous in the Methylococcus genome in the order nifH, nifD and nifK, as found for the majority of other diazotrophs. PMID- 1904042 TI - Revised structure of a trehalose-containing immunoreactive glycolipid of Mycobacterium tuberculosis. AB - Nuclear magnetic resonance spectroscopy, fast-atom bombardment mass spectrometry as well as various chemical degradations and chromatographic techniques were used to re-examine the structure of a highly immunoreactive glycolipid previously described in Mycobacterium tuberculosis (strain Canetti) as a 2,3-diacyl trehalose 2'-sulfate (labelled SL-IV). Ion exchange chromatography allowed the recognition of a neutral and an acidic glycolipid, indistinguishable on conventional silica gel. The neutral glycolipid was shown to be serologically identical to SL-IV and its structure was established as 2,3-diacyl trehalose. It corresponded to the non-chemically defined highly observed immunoreactive lipid previously recognized by others in M. tuberculosis (H37Rv). PMID- 1904043 TI - Pseudomonas aeruginosa isolate typing by esterase electrophoresis. AB - Esterase electrophoretic typing was used to classify clinical isolates of Pseudomonas aeruginosa. One hundred and twenty-seven P. aeruginosa strains belonging to 16 serotypes (including 16 non-typeable strains) and isolated from diverse human infections in three hospitals, and the type strain ATCC 10 145, were tested. Four main kinds of esterase and 4 additional esterases were distinguished by their spectra of hydrolytic activity toward synthetic substrates and by their sensitivity or resistance to di-isopropyl fluorophosphate. The electrophoretic variations of these enzymes were used to define 42 zymotypes. Electrophoretic typing of esterase appeared to be more sensitive than serotyping and the results of the two methods did not correlate. When the two typing methods were used in parallel, 78 different combinations of serotype and zymotype were obtained. PMID- 1904044 TI - One-step purification procedure for UDP-N-acetylmuramyl-peptide murein precursors from Bacillus cereus. AB - A method is described for the rapid isolation of the activated murein precursors UDP-N-acetyl-muramyl-pentapeptide (UDP-MurNAc-pentapeptide) and UDP-MurNAc tripeptide from Bacillus cereus. After accumulation of the precursors by inhibition of murein synthesis either in the presence of vancomycin (for the pentapeptide precursor) or D-cycloserine (for the tripeptide precursor) the cells were extracted with boiling water. Prior to high pressure liquid chromatography the material was freed from acid precipitable material. UDP-MurNAc-penta- and tripeptide were separated from other components by reversed-phase HPLC on Hypersil ODS using isocratic elution conditions with sodium phosphate buffer. The precursors were obtained with at least 98% purity and a yield of about 50 mumol from a 10-l culture of B. cereus. PMID- 1904045 TI - Use of a lacZ fusion to study transcriptional regulation of the Rhodobacter capsulatus hemA gene. AB - An EcoRI fragment containing the Rhodobacter capsulatus hemA promoter has been cloned into a lacZ translational fusion vector. The resulting plasmid produced a hemA-lacZ fusion protein with a molecular mass of 147,000. Expression of the hemA lacZ fusion, as measured by production of beta-galactosidase, was regulated 2- to 3-fold by oxygen tension. The unexpectedly small change in beta-galactosidase levels suggests that transcriptional regulation of the hemA gene is not the major factor in oxygen-mediated control of porphyrin synthesis. PMID- 1904046 TI - Gene mapping and cross-resistance in cyclodiene insecticide-resistant Drosophila melanogaster (Mg.). AB - Resistance to the cyclodiene insecticide dieldrin maps to a single gene (Rdl) on the left arm of chromosome III in Drosophila melanogaster (Meigen). The gene was further mapped by the use of chromosomal deficiencies to a single letter sub region, 66F, on the polytene chromosome. The cross-resistance spectrum of a backcrossed strain lacking elevated mixed function oxidase activity, a common resistance mechanism, was examined. Levels of resistance similar to those found in other insects were found to dieldrin, aldrin, endrin, lindane, and picrotoxinin. Strong similarity of this single major gene with that found in other cyclodiene resistant insects is suggested by its cross-resistance spectrum and chromosomal location, via homology with other Diptera. The significance of major genes in insecticide resistance is discussed. PMID- 1904047 TI - Production of X0 clones in XX females of Drosophila. AB - The experiments reported here are aimed at determining whether mutations deleting the function of the Sex-lethal (Sxl) gene are able to suppress the lethality of X0 clones, induced in females after the time when the state of activity of Sxl is irreversibly fixed by the ratio of the number of X chromosomes to sets of autosomes (X:A). This analysis was carried out by comparing the frequency of induced male clones (X0 constitution) in SxlfLS/+ and Sxl+/Sxl+ females, following irradiation at blastoderm and larval stages. The genotype used in these experiments, however, could also give rise to 2X; 2A cells homozygous for SxlfLS, and such cells would also differentiate male structures. To minimize this possibility, we have constructed a genotype made up of a ring and a rod X chromosome. In such ring-rod females the production of 2X; 2A clones homozygous for SxlfLS is a rather rare event, if possible at all. X0 male clones were produced in both types of females following irradiation at blastoderm stage, while X0 male clones were only observed in SxlfLS/+ females when irradiation took place at larval stage. In this latter case, the only X0 male clones were those that contained the SxlfLS mutation. These results support the idea of Sanchez & Nothiger (1983) that the X:A signal irreversibly sets the state of activity of Sxl at blastoderm stage, and in addition show that X0 clones generated after that time are viable if they contain a Sxl- mutation. These results are compatible with the idea of Sxl being the only gene that responds to the X:A signal. PMID- 1904049 TI - Giant gall bladder diverticulum. AB - Diverticula of the gall bladder are very rare. We present here a patient with a giant diverticulum of the gall bladder with features of cholecystitis and cholelithiasis. PMID- 1904048 TI - The coalescent process in models with selection, recombination and geographic subdivision. AB - A population genetic model with a single locus at which balancing selection acts and many linked loci at which neutral mutations can occur is analysed using the coalescent approach. The model incorporates geographic subdivision with migration, as well as mutation, recombination, and genetic drift of neutral variation. It is found that geographic subdivision can affect genetic variation even with high rates of migration, providing that selection is strong enough to maintain different allele frequencies at the selected locus. Published sequence data from the alcohol dehydrogenase locus of Drosophila melanogaster are found to fit the proposed model slightly better than a similar model without subdivision. PMID- 1904050 TI - Induction of in vitro and in vivo anti-tumor responses by sensitization of mice with liposomes containing a crude butanol extract of leukemia cells and transferred inter-membranously with cell-surface proteins. AB - Generation of cytotoxic T lymphocytes (CTL) in vitro and tumor-rejection responses by sensitization of semi-syngeneic mice with tumor-antigen reconstituted liposomes were investigated. Liposomes were prepared from a crude butanol extract (CBE) of BALBRVD leukemia cells and egg phosphatidylcholine (PC): 1,2-dimyristoylamido-1,2-deoxyphosphatidylcholine (DDPC) (3:2) or dimyristoylphosphatidylcholine (DMPC):DDPC (1:4). Inter-membrane protein transfer (IMPT) liposomes were prepared by incubating BALBRVD cells with DMPC:DDPC (1:4) liposomes. Sensitization of male CB6F1 mice with CBE or IMPT liposomes induced a level of cytotoxicity similar to that on sensitization with mitomycin-C(MMC) treated BALBRVD against BALBRVD target cells after in vitro sensitization with the tumor cells. Sensitization with CBE alone resulted in only marginal cytotoxicity. The cytotoxic effector cells induced by either mode of sensitization were CD8+ T-cells whose recognition was Kd-restricted. No difference in specificity was observed with the different modes of sensitization. Two in vivo immunizations with CBE or with CBE liposomes at a dose of 25 micrograms of protein (equivalent to 2.5 x 10(7) cells) cause moderate inhibition of BALBRVD tumor growth in male CB6F1 mice and immunization with IMPT liposomes at a dose of 1 microgram of protein result in efficient protection. PMID- 1904051 TI - Investigation of the assay of AFB1-albumin adducts using proteolysis products in ELISA. AB - Epidemiological evidence of the involvement of aflatoxins in the aetiology of human liver cancer has led to an increasing interest in the development of appropriate techniques for monitoring human exposure. The assay for aflatoxin adducts in albumin has a better potential for assessing long-term exposure than analyses of urine samples, and several protocols for ELISA of these adducts, following proteolysis of albumin, have been examined. However, there is usually an incomplete release of a major adduct, aflatoxin-lysine, even after prolonged hydrolysis, and the adduct is very unstable under some conditions of proteolysis for unknown reasons. Therefore, before such techniques can be recommended for general application, the significance of such factors in the quantitive estimation of aflatoxin adducts needs to be evaluated. This study has detected the presence of a considerable fraction of aflatoxin-modified material, produced by proteolysis of in vivo aflatoxin-modified rat albumin or in vitro modified bovine albumin, and which is not recognized in ELISA by an anti-aflatoxin polyclonal antibody having a wide spectrum of aflatoxin metabolite detection. This fraction increases in parallel with the proteolysis protocols. PMID- 1904052 TI - Interferon alpha induces expression of the CD69 activation antigen in human resting NK cells, while interferon gamma and tumor necrosis factor alpha are ineffective. PMID- 1904053 TI - Reversible increase in energy deposition following castration induced by a gonadotropin releasing hormone agonist. AB - The effects on energy balance of a potent gonadotropin releasing hormone (GnRH) agonist, have been investigated in rats. Female rats initially weighing 180 g were divided into three groups. One group of rats underwent a bilateral ovariectomy whereas the two remaining groups were sham-operated. Rats in one of the two sham-operated groups were treated with Buserelin which was administrated by means of miniosmotic pumps. The remaining rats were implanted with minipumps that delivered saline. After 28 days of treatment, half of the rats in each group were killed by decapitation whereas the remaining animals had their pumps removed so that the Buserelin treatment stopped. The post-treatment lasted 28 days after which period, rats were killed. Body weight and food intake were measured over every 2 or 3 day periods. Carcasses were analyzed for their contents in protein, fat and energy. During the treatment period, rats that were ovariectomized and those treated with Buserelin increased their food intakes and energy depositions. The increase in energy deposition reflected an increase not only in fat but also in protein deposition. During the post-treatment period, metabolizable energy intake of rats that were administered Buserelin returned to the levels of placebo treated rats. Twenty-eight days post-treatment, the carcass energy contents of the Buserelin-treated rats were no longer different from those of placebo-treated rats. In conclusion, Buserelin induces an increase in energy deposition that is readily reversed upon cessation of the treatment. PMID- 1904054 TI - Host-parasite relationships of Ascogregarina chagasi (Eugregarinorida, Aseptatorina, Lecudinidae) in Lutzomyia longipalpis (Diptera: Psychodidae). AB - The life cycle of Ascogregarina chagasi in larvae and in adult female Lutzomyia longipalpis was studied by light and electron microscopy. Sporozoites and young gamonts were attached to the epithelial lining of the larval midgut via an osmiophilic contact zone. The mucron of young gamonts was bordered by an invaginated pellicular fold, and an electron-opaque vesicular structure was observed adjacent to it. Sporozoites possessed an apical complex and were bound by a double membrane with underlying subpellicular microtubules. The gamont pellicle was uniformly corrugated and consisted of two cortical membranes and a plasma membrane. Mature gamonts and gametocysts were found in the posterior ectoperitrophic space of third and fourth instar larval midguts and in the haemocoel of adult flies. Gametocysts in adult females adhered to the genital accessory glands, where they were encased in electron-dense capsules secreted by the fly through haemocyte-mediated humoral immune reactions. Oocytes were spindle shaped and bound by a double-layered wall with a discernible polar plug at each end. Sporulation was endogenous, occurring within gametocysts in the midguts of larvae or the accessory glands of adult females. FITC-phalloidine staining of all stages of A. chagasi except mature gametocysts produced bright fluorescence, indicating the presence of a diffuse, actin-like protein in the cytoplasm. PMID- 1904055 TI - The tryptophan synthase alpha 2 beta 2 complex. Cleavage of a flexible loop in the alpha subunit alters allosteric properties. AB - This study explores the catalytic and allosteric roles of a flexible loop in tryptophan synthase. Trypsin is known to cleave the tryptophan synthase alpha 2 beta 2 complex in an alpha subunit loop at Arg-188. Cleavage yields an active "nicked" alpha 2 beta 2 derivative. The new results provide evidence that the alpha subunit loop serves two important roles: substrate binding and communicating the effects of substrate binding to the beta subunit. A role for the loop in substrate binding is supported by our finding that addition of a substrate analogue of the alpha subunit, alpha-glycerol 3-phosphate, decreases the rate of cleavage by trypsin. An allosteric role for the loop is supported by the finding although the native alpha 2 beta 2 complex is strongly inhibited by alpha-glycerol 3-phosphate, the nicked alpha 2 beta 2 complex is desensitized to this inhibition. The time course of proteolysis in the presence and absence of alpha-glycerol 3-phosphate is followed by sodium dodecyl sulfate-gel electrophoresis and by assays of activity in the presence and absence of alpha glycerol 3-phosphate. We use spectroscopic measurements of the pyridoxal phosphate-L-tryptophan intermediates at the active site of the beta subunit to determine the affinity of the native and nicked enzymes for L-tryptophan and alpha-glycerol 3-phosphate. Although cleavage alters the equilibrium distribution of intermediates and reduces the affinity for alpha-glycerol 3-phosphate, it has little effect on the affinity for amino acids bound to the beta subunit. We conclude that the loop in the alpha subunit is important for ligand binding and for communicating the effects of ligand binding from the alpha subunit to the beta subunit in the alpha 2 beta 2 complex. PMID- 1904056 TI - Identifying the recognition unit for G protein methylation. AB - Signal transducing G proteins, such as transducin, are prenylated and methylated at carboxyl-terminal cysteine residues. The methylation of transducin occurs by means of a membrane bound S-adenosyl methionine-dependent methyltransferase. This methyltransferase accepts the simple modified amino acid N-acetyl-S-farnesyl-L cysteine (AFC) as a substrate. This means that the enzyme does not require peptide sequences of transducin in a putative substrate. Moreover, small structural changes in the AFC structural unit all lead to molecules incapable of being substrates. For example, neither N-acetyl-S-farnesylhomocysteine (AFHC) nor the saturated form of AFC are substrates. Interestingly, substitution of the N acetyl moiety of AFC with a hydrogen atom leads to S-farnesylthiopropionic acid (FTP), which is an excellent substrate for the methyltransferase. The methyltransferase shows great specificity for the the FTP pharmacophore. So far, alterations in this structure have not led to active substrates. For example, removal of a methylene group of FTP, producing S-farnesylthioacetic acid (FTA), abolished substrate activity. FTA is a potent competitive inhibitor of the enzyme. FTP is thus the ultimately simplified substrate for the methyltransferase and does not contain any remnants of the peptide structure of transducin. PMID- 1904057 TI - Cell-free biosynthesis of lipophosphoglycan from Leishmania donovani. Characterization of microsomal galactosyltransferase and mannosyltransferase activities. AB - Incubation of microsomal preparations from Leishmania donovani parasites with UDP [3H]galactose or GDP-[14C]mannose resulted in incorporation of radiolabel into an endogenous product that exhibited the chemical and chromatographic characteristics of the parasite's major surface glycoconjugate, lipophosphoglycan. The [3H]galactose- or [14C]mannose-labeled product was (i) cleaved by phosphatidylinositol-specific phospholipase C; (ii) deaminated by nitrous acid; and (iii) degraded into radioactive, low molecular weight fragments upon hydrolysis with mild acid. Analysis of the products of mild acid hydrolysis revealed the presence of phosphorylated Gal-beta-Man as the major fragment with lesser amounts of mono-, tri-, and tetrasaccharides. The incorporation of the two isotopic precursors was neither stimulated by the addition of dolichylphosphate nor inhibited by amphomycin, indicating that dolichol-saccharide intermediates are not involved in assembly of the repeating units of lipophosphoglycan. Development of this cell-free glycosylating system will facilitate further studies on the pathway and enzymes involved in lipophosphoglycan biosynthesis. PMID- 1904058 TI - Clusterin (complement lysis inhibitor) forms a high density lipoprotein complex with apolipoprotein A-I in human plasma. AB - Clusterin/human complement lysis inhibitor (CLI) is incorporated stoichiometrically into the soluble terminal complement complex and inhibits the cytolytic reaction of purified complement components C5b-9 in vitro. Using an anti-clusterin affinity column, we found that an additional protein component with a molecular mass of 28-kDa co-purifies with clusterin from human plasma. We show by immunoblotting and amino acid sequencing that this component is apolipoprotein A-I (apoA-I). By using physiological salt buffers containing 0.5% Triton X-100, apoA-I is completely dissociated from clusterin bound to the antibody column. Free clusterin immobilized on the antibody-Sepharose selectively retains apoA-I from total human plasma. Delipidated apoA-I and to a lesser extent ultracentrifugation-purified high density lipoproteins (HDL) adsorbed to nitrocellulose also have a binding affinity for purified clusterin devoid of apoA I. The isolated apoA-I-clusterin complex contains approximately 22% (w/w) lipids which are composed of 54% (mole/mol) total cholesterol (molar ratio of unesterified/esterified cholesterol, 0.58), 42% phospholipids, and 4% triglycerides. In agreement with the low lipid content, apoA-I-clusterin complexes are detected only in trace amounts in HDL fractions prepared by density ultracentrifugation. In free flow isotachophoresis, the purified apoA-I-clusterin complex has the same mobility as the native clusterin complex in human plasma and is found in the slow-migrating HDL fraction of fasting plasma. Our data indicate that clusterin circulates in plasma as a HDL complex, which may serve not only as an inhibitor of the lytic terminal complement cascade, but also as a regulator of lipid transport and local lipid redistribution. PMID- 1904059 TI - Human plasma and recombinant factor VII. Characterization of O-glycosylations at serine residues 52 and 60 and effects of site-directed mutagenesis of serine 52 to alanine. AB - Factor VII is a multidomain, vitamin K-dependent plasma glycoprotein that participates in the extrinsic pathway of blood coagulation. Earlier studies demonstrated a novel disaccharide (Xyl-Glc) or trisaccharide (Xyl2-Glc) O glycosidically linked to serine 52 in human plasma factor VII (Nishimura, H., Kawabata, S., Kisiel, W., Hase, S., Ikenaka, T., Shimonishi, Y., and Iwanaga, S. (1989) J. Biol. Chem. 264, 20320-20325). In the present study, human plasma and recombinant factor VII were isolated and subjected to enzymatic fragmentation. Peptides comprising residues 48-62 of the first epidermal growth factor-like domain of each factor VII preparation were isolated for comparative analysis. Using a combined strategy of amino acid sequencing, carbohydrate and amino acid composition analysis, and mass spectrometry, three different glycan structures consisting of either glucose, glucose-xylose, or glucose-(xylose)2 were detected O-glycosidically linked to serine 52 in plasma and recombinant factor VII. Approximately equal amounts of the three glycan structures were observed in plasma factor VII, whereas in recombinant factor VII the glucose and the glucose (xylose)2 structures predominated. In addition to the O-linked glycan structures observed at serine 52, a single fucose was found to be covalently linked at serine 60 in both human plasma and recombinant factor VII. Carbohydrate and mass spectrometry analyses indicated that the fucosylation of serine 60 was virtually quantitative. Metabolic labeling studies using [14C]fucose confirmed the presence of O-linked fucose at serine 60. In order to assess whether the carbohydrate moiety at serine 52 contributes to the biological activity of factor VII, we have constructed a site-specific mutant of recombinant factor VII in which serine 52 has been replaced with an alanine residue. Mutant factor VIIa exhibited approximately 60% of the coagulant activity of wild-type factor VIIa in a clotting assay. The amidolytic activity of mutant factor VIIa was indistinguishable from that observed for recombinant wild-type factor VIIa. In addition, the ability of mutant factor VIIa in complex with either purified relipidated tissue factor apoprotein or tissue factor on the surface of a human bladder carcinoma cell line (J82) to activate either factor X or factor IX was virtually identical to that observed for wild-type factor VIIa. These results indicate that the carbohydrate moiety O-glycosidically linked to serine 52 does not appear to be involved either in the interaction of factor VIIa with tissue factor, or the expression of its proteolytic activity toward factor X or factor IX following complex formation with tissue factor.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1904060 TI - Hormone-induced calcium oscillations in liver cells can be explained by a simple one pool model. AB - Hormone-induced oscillations of the free intracellular calcium concentration are thought to be relevant for frequency encoding of hormone signals. In liver cells, such Ca2+ oscillations occur in response to stimulation by hormones acting via phosphoinositide breakdown. This observation may be explained by cooperative, positive feedback of Ca2+ on its own release from one inositol 1,4,5 trisphosphate-sensitive pool, obviating oscillations of inositol 1,4,5 trisphosphate. The kinetic rate laws of the associated model have a mathematical structure reminiscent of the Brusselator, a hypothetical chemical model involving a rather improbable trimolecular reaction step, thus giving a realistic biological interpretation to this hallmark of dissipative structures. We propose that calmodulin is involved in mediating this cooperativity and positive feedback, as suggested by the presented experiments. For one, hormone-induced calcium oscillations can be inhibited by the (nonphenothiazine) calmodulin antagonists calmidazolium or CGS 9343 B. Alternatively, in cells overstimulated by hormone, as characterized by a non-oscillatory elevated Ca2+ concentration, these antagonists could again restore sustained calcium oscillations. The experimental observations, including modulation of the oscillations by extracellular calcium, were in qualitative agreement with the predictions of our mathematical model. PMID- 1904062 TI - Bryostatins selectively regulate protein kinase C-mediated effects on GH4 cell proliferation. AB - The phorbol ester tumor promoter, 12-O-tetradecanoylphorbol-13-acetate [TPA) or phorbol 12-myristate 13-acetate), directly activates the calcium- and phospholipid-dependent protein kinase C (protein kinase C), which, in turn, generates a number of cellular responses. The bryostatins, a family of macrocyclic lactones isolated from marine bryozoans, also bind to and active protein kinase C. However, they differ from TPA in the selectivity of their responses in that they behave either as agonists or antagonists of protein kinase C actions. We used several bryostatins and TPA to examine the role of protein kinase C in the regulation of GH4C1 rat pituitary tumor cell proliferation. TPA inhibited [3H]thymidine incorporation in GH4 cells in a stereoselective and concentration-dependent manner. Examination of cell cycle distribution by flow cytometry revealed that TPA decreased the percentage of cells in S-phase and proportionally increased the percentage of G1-phase cells. Bryostatin 1 alone did not affect cell proliferation, but prevented the TPA inhibition of cell proliferation. Bryostatin 1 treatment from 30 min to 6 h after TPA treatment also prevented the growth-inhibitory action of TPA, suggesting that prolonged stimulation of protein kinase C is necessary for growth inhibition. Both bryostatin 1 and TPA down-regulated protein kinase C, indicating that down regulation of the enzyme cannot account for the growth inhibitory action of TPA. Bryostatin 2, which differs from bryostatin 1 by a hydroxyl substitution for the acetyl group at the C-7 carbon of the macrocyclic lactone ring (R1), inhibited cell proliferation and did not reduce the growth-inhibitory action of TPA. Bryostatins 3 and 8 (each of which has an ester group in the R1 position, yet contains other structural modifications) are antagonists for TPA inhibition of GH4 cell proliferation like bryostatin 1. We next examined the effect of bryostatins 3 and 8 on cell-substratum adhesion, a cellular response observed after GH4 cells are treated with growth-inhibitory agents. Bryostatin 8 (like bryostatin 1) did not enhance cell-substratum adhesion and blocked the action of TPA. In contrast, bryostatin 3 enhanced cell-substratum adhesion. Because bryostatin 3 blocked TPA inhibition of cell proliferation, yet did not block TPA enhanced cell-substratum adhesion, these responses are not interdependent. We next examined the effect of bryostatin on other growth-inhibitory agents for GH4 cells. Bryostatin 8 blocks the effect of TPA on [3H]thymidine incorporation and the entry of G1 cells into S-phase, but does not block the growth-inhibitory action of thyrotropin-releasing hormone or epidermal growth factor.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1904061 TI - Cloning of the psbK gene from Synechocystis sp. PCC 6803 and characterization of photosystem II in mutants lacking PSII-K. AB - We cloned and sequenced the psbK gene, coding for a small photosystem II component (PSII-K), from the transformable cyanobacterium, Synechocystis sp. PCC 6803, and determined the N-terminal sequence of mature PSII-K. The psbK gene product is processed by cleaving off eight amino acid residues from the N terminus. A mutant lacking psbK was constructed; this mutant grew photoautotrophically, but its growth rate was reduced. The number of photosystem II reaction centers on a chlorophyll basis was decreased by less than a factor of 2 in the psbK-deletion mutant. In Synechocystis sp. PCC 6803, the psbK gene is transcribed as a single gene and is not part of an operon. Single-site mutations were introduced into psbK leading to early termination or deletion of the presequence. The phenotype of these mutants strongly resembles that of the psbK deletion mutant, indicating that indeed the change in phenotype in the deletion mutant is directly correlated with PSII-K. PSII-K is not essential for photosystem II assembly or activity but is needed for optimal photosystem II function. PMID- 1904063 TI - Deletion of the linker connecting the catalytic and cellulose-binding domains of endoglucanase A (CenA) of Cellulomonas fimi alters its conformation and catalytic activity. AB - The Pro-Thr box is a linker of 23 amino acids ((PT)4T(PT)7) connecting the catalytic domain and the cellulose-binding domain (CBD) of endoglucanase A (CenA) from the bacterium Cellulomonas fimi. Deletion of the Pro-Thr box alters the conformation of CenA by changing the relative orientation of the catalytic domain and the CBD. The tertiary structures of the catalytic domain and the CBD appear to be unchanged. The change in conformation reduces the catalytic efficiency of the enzyme and masks one of two protease-sensitive sites between the domains. The deletion does not affect the adsorption of the enzyme to microcrystalline cellulose, but it does affect its desorption from cellulose. The results suggest that the Pro-Thr box in CenA has an extended, kinked, and rigid conformation. PMID- 1904065 TI - The NH2-terminal extension of high molecular weight bFGF is a nuclear targeting signal. AB - Basic fibroblast growth factor (bFGF) is a member of the heparin-binding growth factor (HBGF) family that includes at least seven species. These proteins are potent regulators of a number of cellular processes, including cell division and angiogenesis. Multiple forms of bFGF exist differing only in the length of their NH2-terminal extensions. These species of bFGF also have unique subcellular distributions. The smallest form (18 kD) occurs predominantly in the cytosol, while the higher molecular weight forms (22, 22.5, 24 kD) are associated with the nucleus and ribosomes. Here we report that the nuclear localization of the higher molecular weight forms of bFGF derives specifically from the amino acid sequences within the NH2-terminal extension. This has been demonstrated by constructing a chimeric protein containing the NH2-terminal extension of the highest molecular weight form of bFGF fused to beta-galactosidase (beta-gal). After transfection in a transient expression system, the chimeric protein accumulated in the nuclei of transfected cells, while the wild-type beta-gal was found predominantly in the cytoplasm. PMID- 1904064 TI - Nonlysosomal, pre-Golgi degradation of unassembled asialoglycoprotein receptor subunits: a TLCK- and TPCK-sensitive cleavage within the ER. AB - The human asialoglycoprotein receptor subunit H2a is cotranslationally inserted into the ER membrane. When expressed together with subunit H1 in mouse fibroblasts part forms a hetero-oligomer that is transported to the cell surface, but when expressed alone it is all rapidly degraded. Degradation is insensitive to lysosomotropic agents and the undegraded precursor is last detected in the ER region of the cell. Small amounts of an intermediate 35-kD degradation product can be detected (Amara, J. F., G. Lederkremer, and H. F. Lodish. 1989. J. Cell Biol. 109:3315). We show here that the oligosaccharides on both precursor H2a and the 35-kD fragment are Man6-9GlcNAc2, structures typically found in pre-Golgi compartments. Subcellular fractionation shows that the intermediate degradation product does not cofractionate with the lysosomal enzyme beta-galactosidase, but is found in a part of the ER that contains ribosomes. Thus the intermediate degradation product is localized in the ER, indicating that the initial degradation event does take place in the ER. All degradation of H2a, including the initial endoproteolytic cleavage generating the 35-kD intermediate, is blocked by the protease inhibitors N-tosyl-L-lysine chloromethyl ketone and N tosyl-L-phenylalanine chloromethyl ketone. These drugs do not inhibit ER-to-Golgi transport of H1. Depleting the cells of ATP or inhibiting protein synthesis allows the initial endoproteolytic cleavage to occur, but blocks further degradation of the 35-kD intermediate; thus we can convert all cellular H2 into the 35-kD intermediate. Approximately 50% of H2b, a splicing variant differing from H2a by a five amino acid deletion, can be transported to the cell surface, and the rest appears to be degraded by the same pathway as H2a, both when expressed alone in fibroblasts and together with H1 in HepG2 cells. Addition of N tosyl-L-lysine chloromethyl ketone or N-tosyl-L-phenylalanine chloromethyl ketone blocks degradation of the approximately 50% that is not transported, but does not affect the fraction of H2b that moves to the Golgi region. Thus, a protein destined for degradation will not be transported to the Golgi region if degradation is inhibited. PMID- 1904066 TI - A possible acute MI: what location and type? PMID- 1904067 TI - Decrease in skin collagen glycation with improved glycemic control in patients with insulin-dependent diabetes mellitus. AB - Glycation, oxidation, and nonenzymatic browning of protein have all been implicated in the development of diabetic complications. The initial product of glycation of protein, fructoselysine (FL), undergoes further reactions, yielding a complex mixture of browning products, including the fluorescent lysine-arginine cross-link, pentosidine. Alternatively, FL may be cleaved oxidatively to form N(epsilon)-(carboxymethyl)lysine (CML), while glycated hydroxylysine, an amino acid unique to collagen, may yield N(epsilon)-(carboxymethyl)hydroxylysine (CMhL). We have measured FL, pentosidine, fluorescence (excitation = 328 nm, emission = 378 nm), CML, and CMhL in insoluble skin collagen from 14 insulin dependent diabetic patients before and after a 4-mo period of intensive therapy to improve glycemic control. Mean home blood glucose fell from 8.7 +/- 2.5 (mean +/- 1 SD) to 6.8 +/- 1.4 mM (P less than 0.005), and mean glycated hemoglobin (HbA1) from 11.6 +/- 2.3% to 8.3 +/- 1.1% (P less than 0.001). These changes were accompanied by a significant decrease in glycation of skin collagen, from 13.2 +/ 4.3 to 10.6 +/- 2.3 mmol FL/mol lysine (P less than 0.002). However, levels of browning and oxidation products (pentosidine, CML, and CMhL) and fluorescence were unchanged. These results show that the glycation of long-lived proteins can be decreased by improved glycemic control, but suggest that once cumulative damage to collagen by browning and oxidation reactions has occurred, it may not be readily reversed. Thus, in diabetic patients, institution and maintenance of good glycemic control at any time could potentially limit the extent of subsequent long-term damage to proteins by glycation and oxidation reactions. PMID- 1904068 TI - Inhibition of immune functions by antiviral drugs. AB - Immune functions were evaluated in vitro for PBMC isolated from healthy donors and cultured with the antiviral agents, 3'-azido-3'-deoxythymidine (AZT), ribavirin, ganciclovir, 2'3'-dideoxyinosine (ddI), or acyclovir. To identify methods for assessing the effects of antiviral drugs on immune cells, the PBMC response to mitogens, Con A, or phytohemagglutinin was evaluated from measurements of [3H]thymidine and [14C]-leucine incorporation, cell growth, cellular RNA, DNA, and protein levels, and the PBMC proliferative cycle (i.e., progression from G0----G1----S----G2 + M). At clinically relevant concentrations, AZT, ribavirin, or ganciclovir diminished PBMC responsiveness to mitogen. The numbers of proliferating cells in G1, S, and G2 + M phases of the cell cycle, DNA content, and [3H]thymidine uptake were decreased in cultures treated with AZT, ribavirin, or ganciclovir. AZT or ribavirin but not ganciclovir reduced RNA and protein in the cultures and inhibited cell growth. Whereas AZT, ribavirin, or ganciclovir were antiproliferative, ddI or acyclovir had little, if any, effect on PBMC mitogenesis. The inhibitory effects of antivirals on immune cells may contribute to the immune deterioration observed in patients following prolonged use of the drugs. PMID- 1904069 TI - Staphylococcal endo-beta-N-acetylglucosaminidase inhibits response of human lymphocytes to mitogens and interferes with production of antibodies in mice. AB - The effect of a bacteriolytic enzyme, the endo-beta-N-acetylglucosaminidase excreted by Staphylococcus aureus (SaG) on the response of human lymphocytes to mitogens and on the immune response in mice has been studied. SaG inhibited incorporation of [3H]thymidine into TCA-precipitable material by human peripheral lymphocytes stimulated either by phytohemagglutinin or by concanavalin A, as well as formation of cytoplasmic immunoglobulin-containing cells by B lymphocytes treated with pokeweed mitogen. In all cases the level of inhibition first increased with the SaG concentrations reaching values of over 80% at an enzyme concentration of 100 micrograms/ml, and then decreased. Heat-inactivated SaG as well as SaG treated with both polyclonal and monoclonal specific antibodies or enzyme inhibitors such as chitotriose or hydrolyzed peptidoglycan had no effect on lymphocyte response to mitogens. In mice, SaG at a dose of 300 micrograms per mouse was found to cause a fourfold decrease in the anti-BSA antibody titer and an approximately 70-75% reduction in the immunoglobulin-containing cells in the spleens of mice injected with sheep red blood cells. SaG also completely abolished the enhancing effect of adjuvants such as muramyldipeptide, Freund's complete adjuvant, and Escherichia coli lipopolysaccharide. When SaG was injected into mice together with S. aureus peptidoglycan hydrolyzed either by SaG or by human lysozyme, the inhibitory effect on both production of anti-BSA circulating antibodies and appearance of Igc cells in the spleens of mice injected with sheep red blood cells was enhanced. As we know that (a) human tissues contain endo-beta N-acetylglucosaminidases; (b) other human hexosaminidases (lysozymes) have previously been shown to interfere with the functions of immunocompetent cells; and (c) products of hexosaminidase hydrolysis of peptidoglycan (muropeptides) known to modulate immune response are ordinarily found in the urine of healthy persons, the possibility that hexosaminidases play a major role in the regulation of the immune response is raised and discussed. PMID- 1904070 TI - Differential adhesion of Pseudomonas aeruginosa to human respiratory epithelial cells in primary culture. AB - Human nasal polyps in outgrowth culture were used to study the Pseudomonas aeruginosa adhesion to respiratory cells. By scanning electron microscopy, P. aeruginosa were seen associated with ciliated cells, but by transmission electron microscopy, bacteria were never seen at the interciliary spaces or attached along cilia, but were identified trapped at the extremities of cilia, usually as bacterial aggregates. A fibronectin-containing fibrillar material was seen associated with aggregated bacteria. By time-lapse video microscopy, bacteria were seen to aggregate in the culture medium following their addition to the culture wells. Progressively, these aggregates were trapped by cilia or attached to migrating cells of a lower cell layer that protruded beneath the upper layer cells, at the outgrowth periphery. P. aeruginosa adhesion to these lower cell layer migrating cells was significantly higher than to ciliated or nonciliated cells of the upper cell layer. Migrating cells were intensely labeled by the complexes Con A and arachis hypogea agglutinin (PNA)-FITC, in contrast to the other cells. The percentage of PNA-labeled cells with attached bacteria was significantly higher than that without bacteria. These results suggest that changes of cell surface glycoconjugates related with cell migration may favor P. aeruginosa adhesion to respiratory cells. PMID- 1904071 TI - Biological and biochemical characterization of a factor produced spontaneously by adherent cells of human immunodeficiency virus-infected patients inhibiting interleukin-2 receptor alpha chain (Tac) expression on normal T cells. AB - Adherent cells from human immunodeficiency virus (HIV)-infected subjects but not from normal blood donors, patients with Gram-positive or -negative bacteremia, active tuberculosis, toxoplasmosis, pulmonary aspergillosis, and cytomegalovirus infection produce spontaneously an activity which inhibits alpha chain of interleukin-2 (Tac) expression and interleukin 2 (IL-2) production by normal activated T cells and IL-2 production by these cells. A similar biologic activity was detected in culture supernatants of in vitro HIV-I-infected normal adherent and leukemic U937 cells. Tac-inhibitory activity is not cytotoxic and it could be detected in serum-free conditioned media. Recombinant granulocyte/macrophage colony-stimulating factor and phorbol myristate acetate stimulation of patients' and normal adherent cells did not enhance specifically the production of the Tac inhibitor. Biologically active conditioned media did not contain infectious virus as well as secreted p24, gp120 viral proteins; the biologic activity could not be abolished by anti-p24, anti-gp120, and anti-nef monoclonal antibodies or human purified polyclonal anti-HIV IgG. Gel filtration of conditioned media followed by anion exchange chromatography resulted in a 1,200-fold degree of purification and revealed that the biologically active molecule was cationic. Sodium dodecyl sulfate polyacrylamide gel electrophoresis of this fraction and gel elution of the proteins showed that the biologic activity was associated with a 29-kD protein which was distinct from alpha- or gamma-interferon, tumor necrosis factor alpha, and prostaglandin E2. The above findings demonstrate the production of inhibitory factor(s) during HIV infection, which might be involved in the pathogenesis of the patients' immune defect. PMID- 1904072 TI - Structure of a monoclonal kappa chain of the V kappa IV subgroup in the kidney and plasma cells in light chain deposition disease. AB - That structural abnormalities may be responsible for nonamyloid immunoglobulin (Ig) light chain deposition disease (LCDD) is suggested by previous results of Ig biosynthesis studies, but this hypothesis was not documented at the molecular level. We report on the first complete primary sequence deduced from cDNA analysis of a kappa light chain responsible for LCDD associated with an apparently nonsecretory myeloma. Bone marrow myeloma cells contained intracellular kappa chains and no heavy chains by immunofluorescence. Kidney biopsy showed typical nonamyloid PAS-positive kappa chain deposits. SDS-PAGE analysis of material extracted from a kidney biopsy specimen and of Ig produced by the myeloma cells revealed kappa chains of abnormally high apparent molecular mass (30,000). Comparison of the NH2-terminal aminoacid sequence of the kappa chain deposited in the kidney and of the complete sequence of several identical kappa cDNA clones from bone marrow cells showed the identity of the tissue deposited and plasma cell kappa chain. The kappa mRNA had an overall normal structure and corresponded to the V kappa IV gene rearranged to J kappa 1 and followed by a normal constant exon of the Km(3) allotype. The variable sequence differed from the V kappa IV germline gene by nine point mutations, including an Asp----Asn substitution at position +70 resulting in a potential N-glycosylation site. In vitro biosynthesis experiments and treatment with N-glycosidase provided evidence for the intracellular glycosylation of the monoclonal kappa chain. The peculiar sequence and the glycosylation of a kappa chain of the rare V kappa IV subgroup might be responsible for structural abnormalities leading to tissue deposition. PMID- 1904074 TI - Complement-mediated inactivation of interferon-gamma in ELISA systems. AB - The recovery of a predetermined amount of interferon-gamma (IFN-gamma) added to normal serum was studied in two independent sandwich ELISA systems specific for rat and human IFN-gamma. In both assays the ELISA activity was rapidly lost in fresh but not in heat-inactivated (30', 56 degrees C) serum. Ninety percent of the initial activity had disappeared within 30 minutes upon incubation at 37 degrees C. Serum-mediated inhibition was not species-specific as the ELISA activity of rat IFN-gamma diminished equally well in rat and human sera. Inhibition was critically dependent on the isotype of the solid-phase monoclonal antibody (mAb) used in the ELISA systems. IgG1 and IgG2a mAbs efficiently inhibited the ELISA activity of IFN-gamma, whereas an IgA mAb was ineffective. The inhibition was not influenced by a wide variety of anti-proteolytic agents but was effectively blocked by anti-complementary substances or treatments directed to the first (C1) and third (C3) component of complement. Our results indicate that activation of the classical pathway of complement (CPC) and the concomitant covalent binding of C3 to the IFN-gamma molecule play a major role in the inhibitory process. It is concluded that reduction of the ELISA activity is attributable to diminished accessibility of the detector antibody for the IFN gamma protein as a consequence of C3 binding. PMID- 1904073 TI - Acetylcholine receptor-reactive T and B cells in myasthenia gravis and controls. AB - Myasthenia gravis (MG) is strongly associated with antibodies to acetylcholine receptor (AChR), whereas the extent of T cell involvement is not settled. The number of cells secreting interferon-gamma (IFN-gamma) in response to AChR during 48 h culture of blood mononuclear cells (PBL) may reflect AChR-reactive T cells. Using an immunospot assay, we detected such cells in 23 of 30 patients with MG at a mean number of 1 per 33.333 PBL. AChR-reactive T cells were also found in patients with other neurological diseases (OND) and in healthy subjects but at lower frequencies and numbers. The T cell response to purified protein derivative and to PHA, and also to two major myelin proteins (basic protein and proteolipid protein) did not differ between MG and the two control groups, underlining the specificity of an augmented T cell reactivity to AChR in MG. Evaluation of the B cell response by enumerating anti-AChR IgG antibody secreting cells revealed such cells in 27 of 28 patients with MG at a mean value of 1 per 14,085 PBL. Cells secreting anti-AChR antibodies of the IgA and IgM isotypes were also detected in MG, but less frequently, at lower numbers, and only in conjunction with IgG antibody secreting cells. Anti-AChR antibody secreting cells were also found among patient with OND and in healthy controls, but at lower frequencies and numbers. These data confirm that AChR is a major target for autoimmune response in MG. PMID- 1904075 TI - Importance of selection of separation system in the development of enzyme immunoassay: an experience with follicle stimulating hormone (FSH) assay. AB - An antiserum to follicle stimulating hormone (FSH) obtained as a gift from National Institute of Health (NIH), U.S.A. could not be adsorbed on microtitre ELISA plates, although two other FSH antisera raised in authors' laboratory could be adsorbed. A good precision profile for the FSH assay using these three antisera could be achieved with only one separation system viz. solid phase anti rabbit gamma globulin (ARGG), out of the five separation systems tried. The study suggests that a few antisera used for radio-immunoassay (RIA) purposes may not by themselves get adsorbed on plastic plates. However, they could be effectively used for ELISA purposes using solid phase second antibody. PMID- 1904076 TI - Potential of parenteral and enteral nutrition in inflammation and immune dysfunction: a new challenge for dietitians. AB - Advances in the understanding of the interrelationship between immunology and nutrition indicate that immune dysfunction in critically ill patients is linked with nutrient deficiency and abnormal acute-phase response to illness. Immune dysfunction requires special nutrition therapy and metabolic support; immunoregulation by nutrition manipulation may lead to specific immunotherapies for defined groups of patients. The success of dietary strategies must be measured not only by metabolic indexes but also by effects on immune function. The health profession must combat immune dysfunction and inflammation for the sick and frail patients under its care. PMID- 1904077 TI - Inhibition of cytolytic lymphocytes by homologous restriction factor. Lack of species restriction. AB - Homologous restriction factor (HRF) has been shown to inhibit complement-mediated lysis in a species-restrictive manner. Human HRF is able to block lysis by human complement but not by complement from other species. HRF has also been found in the membrane of lymphokine-activated killer (LAK) cells. When this HRF is inserted into sheep erythrocyte membranes, it is able to protect the erythrocyte from LAK cell lysis. In this report, we show that while HRF can inhibit human complement but not rat complement-mediated hemolysis, it is able to inhibit LAK cell lysis by both human and rat LAK cells. HRF is therefore a more general protective protein than has been previously thought. PMID- 1904078 TI - Analysis of the time course of IFN-gamma mRNA and protein production during primary murine listeriosis. The immune phase of bacterial elimination is not temporally linked to IFN production in vivo. AB - IFN-gamma clearly plays an important role in the murine host response against Listeria monocytogenes, but the time course of its production and its precise role in immunity remain controversial. To address these issues, we sequentially monitored IFN production and bacterial accumulation in vivo in C57B1/6 mice during primary listeriosis. IFN-gamma mRNA levels (measured by Northern blot analysis of freshly isolated splenic RNA) and serum IFN (measured by ELISA) were both maximal on day 1 of infection, decreasing steadily after day 2 to barely detectable levels by days 4 to 6. Significantly, there was no direct relationship between IFN levels and listericidal activity in vivo. Between days 1 and 3, the period of maximal IFN production, host bacterial load (assessed by quantitating live L. monocytogenes/spleen) increased approximately 10- to 50-fold. On the other hand, during the immune phase of infection (between days 5 and 7), a period when both IFN mRNA and protein were barely detectable, the host bacterial load decreased 1,000- to 10,000-fold. The paucity of IFN production in vivo during the immune phase was unexpected in light of previous reports demonstrating abundant in vitro lymphokine release by splenocytes isolated during the same time period. By direct comparisons of IFN production in vivo and in vitro, however, we could show that the late (days 6-7) peak of IFN release observed in Ag-stimulated cultures was an in vitro artifact. By contrast the pattern of spontaneous IFN release (obtained when freshly isolated cells were incubated in the absence of Ag) conformed more closely to that observed in vivo. Because listerial Ag stimulated vigorous lymphokine release in vitro, we sought to determine whether an analogous effect could be observed in vivo. In fact, even the infusion of very large doses of live bacteria (5-20,000,000/mouse) did not stimulate endogenous IFN-gamma production in mice infected for 6 to 7 days. These studies suggest three major conclusions: 1) IFN production in vivo occurs primarily during the early phase of listeriosis; 2) the dramatic decrease in bacterial numbers observed late in infection cannot be directly attributed to increased IFN production by LM-immune T cells; 3) although Ag-driven cultures of freshly isolated cells can provide useful information about the potential lymphokine producing capabilities of Ag-specific T cells, these results have limited relevance in understanding patterns of T cell lymphokine production in vivo. PMID- 1904079 TI - Macrophage cytostatic effect on Trypanosoma musculi involves an L-arginine dependent mechanism. AB - Peritoneal macrophages from mice infected with an extracellular parasite, Trypanosoma musculi were effective in inhibiting parasite proliferation in vitro. This trypanostatic activity could be suppressed by NG monomethyl-L-arginine (NGMMA), a specific inhibitor of a biochemical pathway synthesizing L-citrulline and inorganic nitrogen oxides from L-arginine. Macrophages exerted this in vitro antiproliferative effect from the 10th day of infection on and this activity was maximum around 14th day of infection. Nitrite production paralleled development of macrophage trypanostatic activity. Macrophages collected from BCG-infected mice or treated with IFN-gamma in vitro also exerted a trypanostatic activity which was suppressed by NGMMA. A trypanostatic activity suppressed by NGMMA was also exerted by splenic macrophages from T. musculi-infected mice. Trypanostatic activity of IFN-gamma-treated macrophages was reduced by addition of anti-TNF alpha showing the participation of TNF-alpha in IFN-gamma-mediated macrophage trypanostatic activity. Nitric oxide (NO) gas inhibited T. musculi proliferation. Addition of excess iron reversed the trypanostatic effect of both macrophages and NO gas. All these data showed that, as reported for a broad spectrum of microorganisms, activated macrophages displayed an antimicrobial effect on trypanosomes through the L-arginine: NO pathway that could participate in controlling infection in T. musculi-infected mice before appearance of antibody dependent mechanisms. NO production by activated macrophages could trigger iron loss from critical target enzymes in trypanosomes. PMID- 1904080 TI - Co-expression of full-length and truncated Ig mu-chains in human B lymphocytes results from alternative splicing of a single primary RNA transcript. AB - A survey of Ig synthesis among mu-heavy chain-producing human B cell lines indicated that roughly one-third co-express full length (mu+) and a particular type of truncated mu-chain (designated mu'). The relative molecular size of the intracellular form of this truncated mu-chain and its normal pattern of N glycosylation suggested that mu'-chains were missing a single Ig domain at the protein level. Cell-free translation of polyA+ RNA from mu'-producing human B cell lines generated appropriate mu'-translation products, and Northern blot analysis demonstrated the presence of correspondingly truncated mu'-transcripts in these lines. These results pointed to a pretranslational basis for mu+/mu' co expression. Sequencing of mu+- and mu'-cDNA clones from two human B cell lines showed that mu+- and mu'-transcripts derive from the same primary transcript, with mu'-mRNA formed by a direct leader-to-C mu 1 exon splice such that the heavy chain variable region exon is excluded via a cassette-type alternative splicing mechanism. Southern blot analysis of the rearranged Ig heavy chain genes in one B cell line confirmed that the co-expressed mu+- and mu'-mRNA derive from the same rearranged Ig heavy chain gene. mu'-cDNA clones were readily isolated from normal human bone marrow lymphocytes, whereas peripheral B cells do not appear to express mu'-transcripts. The frequent occurrence of mu'-mRNA in B cell lines, and its high relative expression in untransformed bone marrow lymphocytes attest to a mode of post-transcriptional control of Ig gene expression that may have implications for human B cell development. PMID- 1904082 TI - Identification of enhancer sequences 3' of the rabbit Ig kappa L chain loci. AB - The rabbit is useful for studies of Ig L chain gene expression because of a great disparity in expression of two isotypic forms of the kappa L chain. Normally, K1 is expressed at high levels and K2 is almost silent; expression of K2 increases in mutant or experimentally allotype-suppressed animals. The reasons for the preferential utilization of the K1 isotype have not been fully elucidated. We were interested in looking for second enhancers 3' of the C kappa genes because the absence of a 3' enhancer in the K2 locus could explain the preferential utilization of the K1 isotype. However, we found a strong region of enhancer activity about 7 kb downstream of the C kappa 2 gene. Sequences in this region are highly conserved between rabbit, man, and mouse. There also appears to be a homologous 3' enhancer region in the rabbit K1 locus. We also confirmed earlier reports that the rabbit K1 intron enhancer is inactive in transient transfections into mouse B cells but find that the same construct has low but significant activity in a human B cell line. In a comparable construct the K2 intron enhancer is without activity suggesting possible differential activity of the intronic enhancers. PMID- 1904081 TI - Estrogen regulates the IFN-gamma promoter. AB - The greater immune reactivity of females has been attributed in part to the influence of sex steroid hormones, but the underlying mechanisms are unknown. Here we report evidence that expression of the IFN-gamma gene may be subject to direct hormonal control. In a transient expression assay, the sex steroid 17 beta estradiol markedly increases activity of the IFN-gamma promoter in lymphoid cells that express the appropriate hormone receptor. This effect is mediated by sequences in the 5'-flanking region of the gene, and can augment the effect of T cell-activating agents. Short term exposure to estradiol also increases IFN-gamma mRNA expression in Con A-treated murine spleen cells. Hormonal regulation of this pleiotropic cytokine may account in part for the ability of estrogen to potentiate many types of immune responses, and for the disproportionate susceptibility of females to autoimmune disease. PMID- 1904083 TI - Defective HLA DRA X box binding in the class II transactive transcription factor mutant 6.1.6 and in cell lines from class II immunodeficient patients. AB - 6.1.6 is one of several immunoselected mutants from EBV-transformed human B cell lines that have undergone coordinate loss of expression of all their HLA class II genes. Similar defects have been found in cells from some patients with class II immunodeficiencies. Previous studies have suggested that the defects in 6.1.6 and in the other class II regulatory mutants are in transactive factors required for class II transcription. The defective factors, however, have not been identified. Here we present two lines of evidence that serve to localize the site of action of the factor that is defective in 6.1.6. First, transfected indicator genes linked to HLA DRA promoter fragments that include the conserved X box region are transiently expressed at greatly reduced levels in 6.1.6, compared with the progenitor cell line T5-1. Second, a DNA-protein complex, termed X-A, formed by nuclear extracts from T5-1 with DRA sequences containing the X box and a few bases 5' and 3' to it, is missing with extracts from 6.1.6. Extracts from some but not all patients with class II-negative immunodeficiency also fail to form X A, whereas extracts from class II-negative mutants derived from the Burkitt's line Raji do form an apparently normal X-A complex. The X-A complex contains proteins of approximately 22, 32, 82, and 92 kDa that can be cross-linked to a 5 bromodeoxyuridine-substituted X box probe by UV light. A defect in an X box binding protein, or in a factor required for its binding, is a likely cause for the loss of transcription of the class II genes in 6.1.6. PMID- 1904084 TI - Macrophage NO2- production as a sensitive and rapid assay for the quantitation of murine IFN-gamma. AB - Macrophage production of arginine-derived NO2- provides a simple method for detection and quantitation of interferon-gamma (IFN-gamma) in murine cell culture fluids. When the macrophage cell line RAW 264 is cultured overnight with IFN gamma in the presence of 10 ng/ml LPS, NO2- release, as determined by a simple colorimetric assay, is proportional to the concentration of IFN-gamma and is inhibited by monoclonal antibody to IFN-gamma. A high degree of correlation was obtained when antigen stimulated T lymphocyte supernatants were tested for IFN gamma by ELISA and the NO2- production assay. PMID- 1904085 TI - Soluble HLA-A2.1 restricted peptides that are recognized by influenza virus specific cytotoxic T lymphocytes. AB - The influenza A virus matrix protein derived peptide with amino acids 57-68 (Lys Gly-Ileu-Leu-Gly-Phe-Val-Phe-Thr-Leu-Thr-Val) is recognized by influenza virus HLA-A2 restricted CTL. Because of the large number of hydrophobic residues this peptide is very insoluble. Substitution with a number of polar amino acids resulted in a soluble peptide (Lys-Lys-Ala-Leu-Gly-Phe-Val-Phe-Thr-Leu-Asp-Lys) that was very effective in sensitizing HLA-A2 positive target cells. Further substitution of threonine in position 65 with lysine resulted in a soluble antagonist peptide that inhibited sensitization. Both agonist and antagonist peptides retained 20% of their biological activity when tyrosine was added at the N terminus. Soluble radio-iodinated peptides can now be prepared that will be useful reagents to study the interaction of peptides and class I molecules. PMID- 1904086 TI - Bacteriology of inadequately treated active chronic otitis media in paediatric age group. AB - Haphazardly treated active otitis media was investigated bacteriologically in 214 children. Analysis showed that Pseudomonas aeruginosa was more prevalent than other micro-organisms. Candida was also found in appreciable quantity. The author contends that this was due to inadequate self treatment before these children reported in his hospital. He advocates that decision regarding the chemotherapeutic agent to be used should be based on culture and in vitro sensitivity. PMID- 1904087 TI - The self-priming action of LHRH is under negative FSH control through a factor released by the ovary: observations in female rats in vivo. AB - Female rats were treated with Metrodin (highly purified urinary FSH from menopausal women) or saline during the oestrous cycle. On the day of pro-oestrus they were anaesthesized with phenobarbital and received four repetitive LHRH injections 1 h apart. This treatment with FSH suppressed the unprimed LH response to the first LHRH injection. During the subsequent injections the maximal LHRH self-priming was delayed by 3 h till the fourth LHRH stimulation. At this time, LH release in response to LHRH was equally as high as shown in the saline controls after the second LHRH injection. Ovariectomized rats did not show the self-priming effect and FSH treatment was ineffective in suppressing LHRH-induced LH release. Administration of FSH followed by an additional 4- or 24-h period before LHRH stimulation were equally effective in suppressing the unprimed LH release and delaying (up to 3 h) the maximal priming of LH release by LHRH. Even 4-20-fold increased amounts of LHRH did not affect the suppressed unprimed release of LH after FSH treatment. Treatment with FSH did not change oestradiol and progesterone levels. It was concluded that FSH treatment suppresses the unprimed LHRH-induced LH release and delays maximal LHRH self-priming by enhancing the release of an ovarian factor. PMID- 1904088 TI - Inherited primary hypothyroidism with thyrotrophin resistance in Japanese cats. AB - Mutant cats were developed with non-goitrous primary hypothyroidism. They were clinically characterized by severely retarded growth, mild anaemia and high mortality in the young. They responded markedly to thyroid hormone replacement. Thyroid glands in the mutants were normal in position but slightly reduced in size. Laboratory studies revealed low serum concentrations of thyroxine (T4) and tri-iodothyronine (T3), and increased serum concentrations of TSH. Administration of TRH induced no further increase in TSH. Administration of exogenous TSH after suppression of endogenous TSH by T3 did not increase the serum concentration of T4 in the mutants, in sharp contrast with the threefold increase in serum T4 observed in the normal litter-mates. These findings suggest that the underlying pathogenesis of this disorder is unresponsive to TSH. Moreover, we found that the mutants were transmitted in an autosomal recessive manner. PMID- 1904089 TI - [Study of the mechanism of supporting cells repairing the organ of Corti in terms of cell kinetics--nuclear DNA synthesis of supporting cell of the organ of Corti in the cochlea damaged by nitromin administration]. AB - 3H-thymidine autoradiography in vivo was carried out on normal mature mice, whose organs of Corti were securely damaged by Nitrogen Mustard-N-oxide (nitromin). The cell kinetics of supporting cells of the organ of Corti were examined and relation between these changes and mechanisms of supporting cells to maintain the organ of Corti was discussed in this paper. A few grains in various kinds of supporting cells in S stage, which were not found in control mice without nitromin injection, were discovered. Those were detected in Hensen's cell, Deiters' cell, Claudius' cells, and inner phalangeal cell. Mitosis was seen in one Claudius' cell in addition. Therefore some supporting cells seem to be able to synthesize DNA and proliferate in the acutely damaged organ of Corti even in mature cochlea and those in G0 stage begin to go around cell cycle as occasion demands. Although labelled supporting cells decreased over time, the portion of supporting cell is likely to change in proportion as the extension of damage in the organ of Corti. If this new dynamic change of cell kinetics in the acutely damaged organ of Corti means the reaction to repair the organ of Corti, the supporting cells seem to have a reasonable role to maintain the organ of Corti including repairment of reticular lamina. PMID- 1904090 TI - A controlled trial of insulin infusion and parenteral nutrition in extremely low birth weight infants with glucose intolerance. AB - To determine whether a continuous insulin infusion improves glucose tolerance in extremely low birth weight infants, we conducted a prospective, randomized trial in 24 neonates 4 to 14 days old (mean birth weight 772.9 +/- 128 gm; mean gestational age 26.3 +/- 1.6 weeks). Infants who had glucose intolerance were randomly assigned to receive either intravenous glucose and total parenteral nutrition with insulin through a microliter-sensitive pump or standard intravenous therapy alone. One infant assigned to receive insulin never required it. The groups were similar in birth weight, gestational age, race, gender, medical condition, and energy intake before the study. The mean duration of therapy was 14.6 days (range 7 to 21 days). During the study, the 11 insulin treated infants tolerated higher glucose infusion rates (20.1 +/- 2.5 vs 13.2 +/- 3.2 mg/kg/min (1.1 +/- 0.1 vs 0.7 +/- 0.2 mmol/L); p less than 0.01), had greater nonprotein energy intake (124.7 +/- 18 vs 86.0 +/- 6 kcal/kg/day; p less than 0.01), and had better weight gain (20.1 +/- 12.1 vs 7.8 +/- 5.1 gm/kg/day; p less than 0.01) than the 12 control infants. The incidence of hypoglycemia, electrolyte imbalance, chronic lung disease, and death did not differ between groups. We conclude that a controlled insulin infusion improves and sustains glucose tolerance, facilitates provision of calories, and enhances weight gain in glucose-intolerant premature infants. PMID- 1904091 TI - Effect of intermittent versus continuous enteral feeding on energy expenditure in premature infants. AB - The purpose of this study was to examine whether premature infants have higher rates of energy expenditure and diet-induced thermogenesis during intermittent feeding compared with continuous feeding. Using open-circuit respiratory calorimetry, we measured energy expenditure in 11 premature newborn infants on 2 successive days for 5 to 7 hours during and after either intermittent or continuous feeding. Infants were fed the same quantity of formula each day, either for 5 minutes or by continuous drip for 2 to 3 hours. The order of feeding type was randomized. No response of diet-induced thermogenesis to continuous feeding was found, whereas a peak increase of 15% over baseline was observed after intermittent feeding. Overall energy expenditure during the study period was significantly greater after intermittent compared with continuous feeding (2.18 +/- 0.07 kcal/kg per hour vs 2.09 +/- 0.05 kcal/kg per hour; p less than 0.05). Thus there was a mean 4% difference (range up to 17%) in energy expenditure between the two feeding modes. These results are similar to those obtained with adults and support the concept of the increased energy efficiency of continuous feeding. Further study will be necessary to document whether the increased energy efficiency provided by continuous feeding may be clinically significant. PMID- 1904092 TI - Effect of lactase on infantile colic. PMID- 1904093 TI - Mutation pattern of human immunodeficiency virus gene. AB - Human immunodeficiency viruses (HIVs) show extensive genetic variation. This feature is the fundamental cause of pathogenicity of HIVs and thwarts efforts to develop effective vaccines. To understand the mutation mechanism of these viruses, we analysed nucleotide sequences of env and gag genes of the viruses by use of molecular evolutionary methods and estimated the direction and frequency of nucleotide substitutions. Results obtained showed that the frequency of changes between A and G was extremely high and the mutation pattern of HIVs was distinct from those of nuclear genes of their host cells. This distinction may be caused by the characteristics of the reverse transcription of HIVs. The mutation pattern obtained would be helpful to construct effective antiviral drugs. PMID- 1904094 TI - Phenomenological theory of GC/AT pressure on DNA base composition. AB - We present a phenomenological theory expressing the constraints operating on the (G + C) contents of the three codon positions, i.e., first, second, and third bases of codons, by using the smallest number of constraint parameters having clear physical and genetic meaning. Theoretical curves displaying base composition at each of the three codon sites are given. The agreement between the theoretical curves and the data points of 1277 genes is quite good irrespective of the species from which the DNAs originated; the curves might be universal ones and the constraint parameters might have general biological meanings in relation to the DNA/RNA and protein functions. PMID- 1904095 TI - Sequence analysis and phylogenetic reconstruction of the genes encoding the large and small subunits of ribulose-1,5-bisphosphate carboxylase/oxygenase from the chlorophyll b-containing prokaryote Prochlorothrix hollandica. AB - Prochlorophytes similar to Prochloron sp. and Prochlorothrix hollandica have been suggested as possible progenitors of the plastids of green algae and land plants because they are prokaryotic organisms that possess chlorophyll b (chl b). We have sequenced the Prochlorothrix genes encoding the large and small subunits of ribulose-1,5-bisphosphate carboxylase/oxygenase(rubisco), rbcL and rbcS, for comparison with those of other taxa to assess the phylogenetic relationship of this species. Length differences in the large subunit polypeptide among all sequences compared occur primarily at the amino terminus, where numerous short gaps are present, and at the carboxy terminus, where sequences of Alcaligenes eutrophus and non-chlorophyll b algae are several amino acids longer. Some domains in the small subunit polypeptide are conserved among all sequences analyzed, yet in other domains the sequences of different phylogenetic groups exhibit specific structural characteristics. Phylogenetic analyses of rbcL and rbcS using Wagner parsimony analysis of deduced amino acid sequences indicate that Prochlorothrix is more closely related to cyanobacteria than to the green plastid lineage. The molecular phylogenies suggest that plastids originated by at least three separate primary endosymbiotic events, i.e., once each leading to green algae and land plants, to red algae, and to Cyanophora paradoxa. The Prochlorothrix rubisco genes show a strong GC bias, with 68% of the third codon positions being G or C. Factors that may affect the GC content of different genomes are discussed. PMID- 1904096 TI - Interspecific comparison of the unusually repetitive Drosophila locus mastermind. AB - The mastermind gene of Drosophila melanogaster encodes a novel, highly repetitive nuclear protein required for neural development. To identify functionally important regions we have initiated an interspecific comparison of the gene in Drosophila virilis. Mastermind transcription and genomic organization are similar in both species and sequence analysis reveals significant conservation in a major cluster of charged amino acids. In contrast, extensive variation is noted in homopolymer domains that immediately flank the acidic cluster. Distinct patterns of evolutionary change can be identified: the major difference between unique regions are occasional amino acid substitutions whereas the repetitive areas are characterized by numerous large in-frame insertions/deletions and a nearly threefold higher rate of amino acid replacement. Conservation of the acidic domain suggests that it has an important functional role whereas the hypervariable homopolymer regions appear to be under less selective constraints than adjacent unique areas. PMID- 1904097 TI - ADH and phylogenetic relationships of Drosophila lebanonesis (Scaptodrosophila). AB - Increasing data on Drosophila alcohol dehydrogenase (ADH) sequences have made it possible to calculate the rate of amino acid replacement per year, which is 1.7 x 10(-9). This value makes this protein suitable for reconstructing phylogenetic relationships within the genus for those species for which no molecular data are available such as Scaptodrosophila. The amino acid sequence of Drosophila lebanonensis is compared to all of the already known Drosophila ADHs, stressing the unique characteristic features of this protein such as the conservation of an initiating methionine at the N-terminus, the unique replacement of a glycine by an alanine at a very conserved position in the NAD domain of all dehydrogenases, the lack of a slow-migrating peptide, and the total conservation of the maximally hydrophilic peptide. The functional significance of these features is discussed. Although the percent amino acid identity of the ADH molecule in Drosophila decreases as the number of sequences compared increases, the conservation of residue type in terms of size and hydrophobocity for the ADH molecule is shown to be very high throughout the genus Drosophila. The distance matrix and parsimony methods used to establish the phylogenetic relationships of D. lebanonensis show that the three subgenera, Scaptodrosophila, Drosophila, and Sophophora separated at approximately the same time. PMID- 1904098 TI - Vitellogenin motifs conserved in nematodes and vertebrates. AB - Caenorhabditis elegans vitellogenins are encoded by a family of six genes, one of which, vit-5, has been previously sequenced and shown to be surprisingly closely related to the vertebrate vitellogenin genes. Here we report an alignment of the amino acid sequences of vitellogenins from frog and chicken with those from three C. elegans genes: vit-5 and two newly sequenced genes, vit-2 and vit-6. The four introns of vit-6 are all in different places from the four introns of vit-5, but three of these eight positions are identical or close to intron locations in the vertebrate vitellogenin genes. The encoded polypeptides have diverged from one another sufficiently to allow us to draw some conclusions about conserved positions. Many cysteine residues have been conserved, suggesting that vitellogenin structure has been maintained over a long evolutionary distance and is dependent upon disulfide bonds. In addition, a 20-residue segment shows conservation between the vertebrate and the nematode vitellogenins. This sequence may play a highly conserved role in vitellogenesis, such as specific recognition by oocytes. On the whole, however, selection may be acting more strongly on amino acid composition and codon usage than on amino acid sequence, as might be expected for abundant storage proteins: The amino acid compositions of vit-2, vit 5, and vit-6 products are remarkably similar, despite the fact that the sequence of the vit-2 protein is only 22% and 50% identical to the sequences of vit-6 and vit-5 proteins, respectively. PMID- 1904099 TI - Sequence rearrangements at the ori 7 region of Saccharomyces cerevisiae mitochondrial DNA. AB - Three ori elements (ori 2, ori 5, and ori 7) have been sequenced in Saccharomyces cerevisiae strain Dip 2 and compared to the equivalent ori elements of a second strain (B). Both ori 2 and ori 5 exhibit 98% base matching between strains Dip 2 and B. In contrast, the third ori element (ori 7) exhibits extensive sequence rearrangements whereby a segment located downstream in the consensus strain occurs within the ori structure in Dip 2. This represents a novel polymorphic form of the yeast mitochondrial genome. PMID- 1904100 TI - On the maximum likelihood method in molecular phylogenetics. AB - The efficiency of obtaining the correct tree by the maximum likelihood method (Felsenstein 1981) for inferring trees from DNA sequence data was compared with trees obtained by distance methods. It was shown that the maximum likelihood method is superior to distance methods in the efficiency particularly when the evolutionary rate differs among lineages. PMID- 1904101 TI - 1,25-Dihydroxyvitamin D3 is a potent inducer of nerve growth factor synthesis. AB - 1,25-Dihydroxyvitamin D3 (1,25-(OH)2D3), a metabolically active form of vitamin D, is shown to increase in a dose-dependent manner the cellular pool of NGF mRNA in murine L-929 fibroblasts cultured in a serum-free medium. This effect can be detected as early as 3 hours after 1,25-(OH)2D3 addition and persists for at least 28 hours. It is accompanied by an enhancement of the amount of NGF protein secreted in the culture medium. Since the proto-oncogene c-fos appears involved in the regulation of the NGF gene (Mocchetti et al.: Proceedings of the National Academy of Sciences of the United States of America 86: 3871-895, 1989; Hengerer et al: Proceedings of the National Academy of Sciences of the United States of America 87:3899-3903, 1990), the effect of 1,25-(OH)2D3 on c-fos expression was analysed and compared to that elicited by other inducers of the NGF gene, serum (Wion et al: FEBS Letters 189:37-41, 1985) and phorbol 12-myristate 13-acetate (PMA) (Wion et al: FEBS Letters 262:42-44, 1990). Addition of serum or PMA to L 929 cells was rapidly followed by a transient activation of the c-fos gene. In contrast, c-fos transcripts remained undetected in the presence of 1,25-(OH)2D3. The failure to find any evidence of c-fos expression suggests that 1,25-(OH)2D3 could enhance the pool of NGF mRNA by a mechanism independent of the c-fos pathway.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1904102 TI - Active polysomes in the axoplasm of the squid giant axon. AB - Axons and axon terminals are widely believed to lack the capacity to synthesize proteins, relying instead on the delivery of proteins made in the perikaryon. In agreement with this view, axoplasmic proteins synthesized by the isolated giant axon of the squid are believed to derive entirely from periaxonal glial cells. However, squid axoplasm is known to contain the requisite components of an extra mitochondrial protein synthetic system, including protein factors, tRNAs, rRNAs, and a heterogeneous family of mRNAs. Hence, the giant axon could, in principle, maintain an endogenous protein synthetic capacity. Here, we report that the squid giant axon also contains active polysomes and mRNA, which hybridizes to a riboprobe encoding murine neurofilament protein. Taken together, these findings provide direct evidence that proteins (including the putative neuron-specific neurofilament protein) are also synthesized de novo in the axonal compartment. PMID- 1904104 TI - Gastroenterology and hepatology. PMID- 1904103 TI - In vitro binding of human T-cell leukemia virus rex proteins to the rex-response element of viral transcripts. AB - Human T-cell leukemia virus (HTLV-I, HTLV-II) rex protein function is required for the cytoplasmic expression of incompletely spliced viral transcripts encoding structural proteins. The effect is mediated by a cis-acting rex-response element (RRX) which is located near the 3' end of all viral mRNAs. We show that rex polypeptides of HTLV-I and HTLV-II expressed in Escherichia coli are capable of specifically binding RRX-containing transcripts of both viruses in cell-free assays. Binding analyses with deletion variants of rex proteins revealed a domain with RNA-binding activity in the first 77 N-terminal amino acids. Removal of a basic peptide of 19 amino acids from the N terminus abrogated RNA binding, whereas a beta-galactosidase fusion protein containing this peptide bound to the RRX. These results suggest that direct binding of rex protein to the RRX is important for rex-mediated regulation of viral gene expression and that a short stretch of positively charged amino acids contributes to the specific binding of rex to its target RNA. PMID- 1904105 TI - Obstetrics and gynecology. PMID- 1904106 TI - [Combination antibacterial effects between aztreonam and eight other antibiotics]. AB - In vitro interactions between aztreonam (AZT) and 8 other antibiotics were studied using the agar dilution checkerboard technique against 88 clinical isolates of Escherichia coli, Proteus vulgaris, Serratia marcescens and Pseudomonas aeruginosa. Combinations of AZT with 8 other antibiotics were generally additive or indifferent. Synergism was occasionally seen against S. marcescens or P. aeruginosa with AZT plus isepamicin (ISP). Antagonism was observed only between AZT and latamoxef against P. vulgaris. In a phase-contrast microscopic study, synergistic effects between AZT and aspoxicillin or ISP were confirmed against E. coli 177 and P. aeruginosa 15846. AZT in combination with ISP demonstrated a synergy against experimental urinary tract infection in mice caused by P. aeruginosa 15846. We believe that combinations of several antibiotics with AZT should be considered for initial therapy of infections because synergism and additive action were observed and antagonism was rarely found in our study. PMID- 1904107 TI - [Studies on EDTA-dependent pseudoneutropenia]. AB - The phenomenon of EDTA-dependent pseudoleukocytopenia was observed in seven patients during the period from September 1989 to March 1990. The pseudoleukocytopenia was found to have come from aggregation of neutrophils. The aggregations were composed of neutrophils only, and did not include other granulocytes, monocytes and lymphocytes. The aggregations showed their maximum in size from 30 to 180 minutes after venipuncture at room temperature. The aggregated neutrophils were again dispersed by incubating at 37 degrees C for 30 minutes. The degree of aggregation was found to be dependent on the concentration of EDTA. Neutrophil aggregation was not recognized in the blood films when sodium citrate or heparin was used as an anticoagulant. The results of mercaptoethanol agglutination test and immunocytochemical staining suggest that IgM antibody may play an important role in the formation of neutrophil aggregation. Four of the seven patients had suffered from hepatic disorder. However, the mechanism of EDTA dependent neutrophil aggregation remains uncertain. PMID- 1904108 TI - [Gabexate mesilate induced remarkable transient reversal of thrombocytopenia in a ITP patient]. AB - A 46-year-old woman was admitted to our hospital because of hemorrhagic tendency. Normal coagulation test results conflicted with the diagnosis of disseminated intravascular coagulation (DIC). Furthermore, we saw no evidence of autoantibodies, including antinuclear antibodies and splenomegaly, and there was no past history of infection or medication. Peripheral blood test showed marked decrease of platelets only. Bone marrow aspiration revealed increased megakaryocytes. Morphology of other blood components was normal. Thus, we diagnosed this case as idiopathic thrombocytopenic purpura (ITP). Administration of prednisolone and an immunosuppressants did not improve symptoms. So patient was temporarily discharged and treated with 6-MP at the outpatient department. She was rehospitalized for liver damage caused by the drug. Patient then developed sepsis from acinetobactor. We administered gabexate mesilate (FOY, 2,000 mg/day) for four days to prevent DIC. Platelet count, which was 1.5 X 10(4)/microliter before FOT administration, began increasing on the second day, reaching 25. 5 X 10(4)/microliter on the fourth. Count rapidly decreased to 2.8 X 10(4)/microliter on the seventh day after administration had been discontinued. Two-time FOY administration after patient's recovery from sepsis led to a definite, similar transient increase in platelet count. As ITP patients with transient increase in platelet count by FOY administration had not been reported, this case is thought to be an interesting case in the pathogenesis and treatment of ITP. PMID- 1904109 TI - [Differentiation and maturation of erythroid cells. Their regulatory factors]. PMID- 1904110 TI - [Hemoglobin-biosynthesis, chemical structure and function]. PMID- 1904111 TI - [Molecular biology of erythropoietin]. PMID- 1904112 TI - [A new advance in theory of blood coagulation and fibrinolysis and its practical application]. AB - New trends in tests for coagulation and fibrinolysis and advances in diagnosis for the hypercoagulable state and utilization of immunological techniques such as various polyclonal and monoclonal antibodies are reported. We discussed (1) the new markers for hypercoagulable states, (2) differential diagnosis of disseminated intravascular coagulation (DIC) and abnormalities of coagulation in liver cirrhosis (LC), and (3) new markers for fibrinolysis and vascular function. Thrombin-antithrombin III complex (TAT) levels were higher in thrombotic diseases than in healthy controls. Therefore, TAT should be a good marker for hypercoagulation as fibrinopeptide A (FPA) and soluble fibrin monomer complex (SFMC). Measurement of TAT, plasma-alpha 2 plasmin inhibitor complex (PIC), and D dimer were useful for differential diagnosis of DIC and liver cirrhosis. t-PA-PAI complex correlated well with t-PA, but not with fibrinolytic parameters such as PIC. The t-PA-PAI complex may be a good marker for the function of the vascular endothelium. PMID- 1904113 TI - Deamination of norepinephrine, dopamine, and serotonin by type A monoamine oxidase in discrete regions of the rat brain and inhibition by RS-8359. AB - Levels of monoamines and their metabolites were determined in the cortex, hippocampus, and striatum of rats killed by microwave irradiation. Moclobemide (20 mg/kg, p.o.) and clorgyline (10 mg/kg, p.o.), type A monoamine oxidase (MAO A) inhibitors, increased the levels of normetanephrine (NM) and 3-methoxytyramine (3MT) and decreased those of 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5HIAA) in almost all three regions. Deprenyl (10 mg/kg, p.o.), a type B monoamine oxidase inhibitor, however, little affected monoamine and metabolite levels in all regions. The maximum effects of RS-8359 (10 mg/kg, p.o.) were obtained at 2 to 6 hr after administration, when the levels of norepinephrine (NE), NM, 3MT, and serotonin (5HT) in all regions and dopamine (DA) in the striatum increased, while DOPAC and HVA levels decreased. The levels of monoamines and metabolites had returned to normal by 20 hr after administration. Dose-dependency of the effects of RS-8359 on monoamine metabolites was observed at doses up to 30 mg/kg (p.o.) at 1 and 6 hr after administration. In conclusion, NE, DA, and 5HT are exclusively or preferentially deaminated by MAO-A in the cortex, hippocampus, and striatum of rats, and RS-8359 exhibits a reversible MAO-A inhibitory action in all three regions tested in vivo. PMID- 1904115 TI - Pharmacological study of TA-0910, a new thyrotropin-releasing hormone (TRH) analog (III): Inhibition of pentobarbital anesthesia. AB - Sites and mechanisms of the antagonistic action of TA-0910, a new thyrotropin releasing hormone (TRH) analog, on pentobarbital anesthesia were studied in rats. Intravenous administration of TA-0910 dose-dependently shortened the duration of pentobarbital anesthesia at 30 micrograms/kg or more. The anti-anesthetic action of TA-0910 after intracerebral injection was in the following order of effectiveness: the posterior lateral hypothalamic area greater than midbrain reticular formation greater than raphe nuclei = locus ceruleus greater than anterior lateral hypothalamic area = ventral globus pallidus = hippocampus. TA 0910 injected into the nucleus accumbens, medial septal nucleus, parietal cortex or striatum had no effect, even at high doses. The anti-anesthetic action of TA 0910 (0.1 mg/kg, i.v.) was inhibited by a low dose of scopolamine or mecamylamine and by a high dose of haloperidol, phenoxybenzamine or metergoline. However, physostigmine and oxotremorine showed no anti-anesthetic action alone or in combination with TA-0910 (0.01 mg/kg, i.v.). Pentobarbital anesthesia was not inhibited by carbachol injected into various sites of the brain. These results suggest that the inhibitory effect of TA-0910 on pentobarbital anesthesia is mainly produced by activation of the posterior lateral hypothalamic area and the midbrain reticular formation, and that the involvements of not only acetylcholine but also other neurotransmitters such as dopamine, serotonin, and noradrenaline should be examined for their anti-anesthetic action. PMID- 1904114 TI - Pharmacological study of TA-0910, a new thyrotropin-releasing hormone (TRH) analog (II): Involvement of the DA system in the locomotor stimulating action of TA-0910. AB - The mechanism of the locomotor stimulating action of a new thyrotropin-releasing hormone (TRH) analog, TA-0910, was studied in rats. The locomotor stimulating action of TA-0910 (3 mg/kg) was inhibited by haloperidol or alpha-methyl-p tyrosine (alpha-MT); slightly inhibited by phenoxybenzamine, prazosin, clonidine, or naloxone; not affected by propranolol, metergoline, or a low dose of scopolamine; and was enhanced by a high dose of scopolamine. The locomotor activity was increased by TA-0910 (0.3 mg/kg) in combination with methamphetamine, apomorphine, or L-DOPA under pretreatment with pargyline. A low dose of apomorphine inhibited the increase in locomotor activity induced by TA 0910 (3 mg/kg). The increase in locomotion was most notable and dose-dependent with the injection of 20 ng or more in the nucleus accumbens. The intravenous administration of TA-0910 produced dose-dependent and significant hyperlocomotion at 1 mg/kg or more. In the rats lesioned unilaterally in the nigrostriatal dopamine (DA) pathway by 6-hydroxydopamine, TA-0910 induced ipsilateral circling behavior at 3 mg/kg or more. This circling behavior was inhibited by haloperidol or alpha-MT. These results suggest that the locomotor stimulating action of TA 0910 is mediated primarily via the dopaminergic neuron, especially the nucleus accumbens of the mesolimbic DA system. Other possible mechanisms are also discussed. PMID- 1904116 TI - [Acute and chronic effects of vasodilators in a case of chronic recurrent pulmonary embolism]. AB - A 65-year-old man was admitted to our hospital because of shortness of breath on exertion. As the results of examinations including pulmonary angiography, pulmonary perfusion scan and pulmonary ventilation scan, we diagnosed the case as chronic recurrent pulmonary embolism. Although the patient received thrombolytic therapy by a tissue plasminogen activator (t-PA), there was no noticeable improvement. However, oxygen and vasodilator therapy had marked effective on the hemodynamics. In chronic pulmonary embolism, vasodilators are generally not considered to be effective for improvement of hemodynamics. However, if the acute effects of vasodilators were confirmed, we should try to administer them while paying attention to possible adverse effects. PMID- 1904117 TI - [Immunological assessment of tumour infiltrating lymphocyte subsets in renal cell carcinoma patients. An analysis of immunological reaction to immuno-competent lymphocytes by interferon-gamma]. AB - Twenty-two patients with renal cell carcinoma subjected to radical nephrectomy were divided into 2 groups. The first group consisted of patients who received nephrectomy alone, and the second of 10 patients who received pre-operative IFN gamma. Using monoclonal anti-bodies of each subset of lymphocytes, immunological distributions of tumour infiltrating lymphocytes (TIL) were evaluated by means of immunohistochemical staining and the peripheral blood lymphocytes (PBL) were evaluated by flow-cytometry. Furthermore, immunological effects of IFN-gamma on these immuno-competent cells were investigated. The effect of IFN-gamma on TIL was an increase in CD3 (pan-T cells), in particular an increase in CD8 (suppressor/cytotoxic-T cells). On the other hand, a significant increase in CD16 alone was found on PBL. As to the TIL according to stages, all subset ratios tended to be higher in high stage patients without administration of IFN-gamma. With pre-administration of IFN-gamma, a marked increase in CD3 was found among low stage patients. In examining these cells according to grades, no specific trend was observed between low and high grade patients without having IFN-gamma administration. With pre-administration of IFN-gamma, an increase in CD3 and CD8 was observed in low grade patients. As to PBL, a significant increase in CD16 alone was observed with pre-administration of IFN-gamma, and no correlation was found between stage and grade. We draw the conclusions that the subsets of TIL were quite different from those of PBL.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1904118 TI - [Chemosensitivity test on superficial urinary bladder cancer using the dye exclusion assay--model of intravesical chemotherapy]. AB - A chemosensitivity test was carried out on superficial bladder cancers using the trypan blue dye exclusion assay for the purpose of screening chemosensitive drugs for intravesical chemotherapy. Transplantable murine bladder tumor cells (MBT-2) were incubated, in vitro, in the presence of adriamycin (4, 40, 400, 1000 micrograms/ml) as well as verapamil (3, 30, 100, 500 micrograms/ml) at 5% CO2, 37 degrees C for two hours. After cellular viabilities were calculated, MBT-2 cells were inoculated into the hind limbs of mice. The cellular viability was correlated well with the ratio of tumor appearance, tumor growth inhibition and prolongation of survival, and was dose dependent in the adriamycin treated groups. On the other hand, a reduction of cellular viability, tumor growth inhibition and prolongation of survival were seen in the high dose verapamil (100, 500 micrograms/ml) treated groups. Human superficial bladder cancer cells were incubated in the presence of adriamycin, 4'-0-tetrahydropyranyladriamycin, mitomycin C and pepleomycin (1000 micrograms/ml) and/or verapamil (500 micrograms/ml). The reduction rates of cellular viability markedly varied with the kind of anticancer drugs. A reduction of cellular viability of human tumor cells as well as MBT-2 cells was seen in the verapamil treated groups. This rapid and handy assay seems to be useful for the purpose of screening chemosensitive drugs for intravesical chemotherapy. PMID- 1904119 TI - [Anti-bacterial defense mechanisms of the urinary tract constructed from intestinal segments. Preliminary studies on urinary tract infections, secretory IgA and composition of urine]. AB - The characteristics of urinary tract infections (UTI), secretory IgA and urine composition of 24 patients (intestine group) who underwent operations using intestinal segments in urinary tract were compared with those of 26 complicated UTI patients without surgical intervention (control group). No significant differences were found in the frequency of either mono or polymicrobial infections between both groups. However, the frequency of bacterial isolation was different in the two groups, Streptococcus spp. and Providencia spp. were frequently isolated and P. aeruginosa was rarely isolated from the urine of the intestine group compared with from the urine of the control group. Furthermore, in polymicrobial infections of the intestine group with indwelling catheters, E. faecalis and Providencia spp. were frequently isolated simultaneously. The mean value of urinary secretory IgA was 94.0 micrograms/dl in the intestine group and 25.0 mu/dl in the control group (p less than 0.0001). The mean urinary osmolarity was 370 mOsm/kg in the intestine group and 500 mOsm/kg in the control group (p less than 0.005). The other parameters, including urinary pH and urea N concentration, showed no statistically significant differences. These findings suggest that urinary tract constructed from intestinal segments differs from the urinary tract without surgical intervention in the feature of UTI and anti bacterial defense mechanisms. PMID- 1904120 TI - [Intravesical instillation of bacillus Calmette-Guerin for superficial bladder carcinoma: study on significance of additional maintenance instillations of bacillus Calmette-Guerin]. AB - The efficacy of maintenance bacillus Calmette-Guerin (BCG) instillations for superficial bladder tumors was studied by prospective randomized trial. From June 1985 to October 1988, 42 newly diagnosed patients with superficial bladder carcinoma (pTa or pT1) were treated by transurethral tumor resection and subsequent five daily instillations of mitomycin C. Then they were divided into non-maintenance group (22 patients) and maintenance group (20 patients) by randomization. The patients received six weekly instillations of 80 mg of BCG. Tokyo strain (Japan BCG manufacturing Co., Tokyo, Japan), suspended in 40 ml of physiological saline, and the patients in the maintenance group received four additional instillations of BCG every three months. We could not complete the six week course of BCG instillations in three patients due to adverse effects (two in non-maintenance group and one in maintenance group) and we lost six patients from follow-up within one year (one in non-maintenance group and five in maintenance group). The mean follow-up period of the remaining 33 patients was 28.1 months. Of these 33 patients, six patients had been found to have recurrent tumors, and the over-all three-year non-recurrence rate was 82%. Before employing BCG, when we used only mitomycin C after TUR-Bt, the three year non-recurrence rate was 58%. This indicates prophylactic effect of BCG instillations. The stage of the initial tumor of the six recurrent cases were all pT1b. The non-recurrence rate of the patients with pT1b tumor was significantly lower than that of the patients with pTa and pT1a tumor. However, multiplicity and grade of tumors did not affect the non-recurrence rate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1904121 TI - Ribose administration during exercise: effects on substrates and products of energy metabolism in healthy subjects and a patient with myoadenylate deaminase deficiency. AB - Nine healthy men and a patient with myoadenylate deaminase deficiency were exercised on a bicycle ergometer (30 minutes, 125 Watts) with and without oral ribose administration at a dose of 2 g every 5 minutes of exercise. Plasma or serum levels of glucose, free fatty acids, lactate, ammonia and hypoxanthine and the urinary hypoxanthine excretion were determined. After 30 minutes of exercise without ribose intake the healthy subjects showed significant increases in plasma lactate (p less than 0.05), ammonia (p less than 0.01) and hypoxanthine (p less than 0.05) concentrations and a decrease in serum glucose concentration (p less than 0.05). When ribose was administered, the plasma lactate concentration increased significantly higher (p less than 0.05) and the increase in plasma hypoxanthine concentration was no longer significant. The patient showed the same pattern of changes in serum or plasma concentrations with exercise with the exception of hypoxanthine in plasma which increased higher when ribose was administered. PMID- 1904123 TI - The cell envelope of the hyperthermophilic archaebacterium Pyrobaculum organotrphum consists of two regularly arrayed protein layers: three-dimensional structure of the outer layer. AB - The cell envelope of the hyperthermophilic sulphur-reducing archaebacterium Pyrobaculum organotrophum H10 was found to be composed of two distinct hexagonally arranged crystalline protein arrays. Electron microscopic analysis of freeze-etched cells and isolated envelopes in conjunction with image processing showed that the inner layer (lattice centre-to-centre spacing 27.9 nm) is essentially identical to the protein array of Pyrobaculum islandicum GEO3, a complex, rigid structure implicated in the maintenance of cell shape. The outer layer has clear p6 symmetry and a lattice spacing of 20.6 nm. Its three dimensional structure was reconstructed from a negative stain tilt series of an intact double-layered envelope using Fourier filtration to separate the desired information from the other lattices present. The outer layer is a unique, porous network of blocklike dimers disposed around six-fold axes, and exhibits minimal asymmetry between its inner and outer faces. It appears to be rather loosely associated with the outer surface of the inner layer. In most H10 envelopes, the inner layer is orientated with one base vector exactly perpendicular to the long axis of the cell, so that the cylindrical portion is composed of a series of parallel cell-girdling hoops of hexameric morphological units. All the other known Pyrobaculum strains were found to have a GEO3-type envelope structure, consisting of a single rigid protein array and a fibrous capsule. Although H10 does not possess a capsule, fibrils appear to be sandwiched between the two protein layers. PMID- 1904122 TI - Malnutrition and immune dysfunction in patients infected with human immunodeficiency virus. AB - STUDY OBJECTIVE: To determine forms of malnutrition and basal metabolism at different stages of immunological impairment in clinically stable patients infected with Human Immunodeficiency Virus (HIV). DESIGN: Cross sectional study. SETTING: 53 outpatients with HIV-infection classified according to the Walter Reed staging system (WR1 to WR6). MEASUREMENTS AND MAIN RESULTS: 87% of the patients showed some evidence of malnutrition. Reduced body weight was found in 53%, 68% and 25% had decreases in fat and body cell mass, 17% had visceral protein deficiency, whereas extracellular mass and serum triglyceride concentrations were increased in 58% and 30%, respectively. Reduced serum albumin and transferrin closely paralleled immunological depression, whereas alterations in body composition were manifest early during HIV-infection (WR3) and remained unchanged during the transition to the Acquired Immune Deficiency Syndrome itself. Resting metabolic rate increased from WR1 to WR3; it remained within the expected range during later stages (WR4-WR6), but was not appropriately reduced in response to the loss in body cell mass. CONCLUSIONS: HIV-infected patients display both, calorie and protein malnutrition. Immunological depression was independent of loss of body mass, but was closely associated to decreases in serum albumin values. Nutritional assessment and intervention should therefore be performed at an early stage of HIV-infection. PMID- 1904124 TI - Identification of gene products of the P1 operon of Mycoplasma pneumoniae. AB - Gene P1 of Mycoplasma pneumoniae, which codes for a major adhesin, is flanked by two sequences with open reading frames designated ORF4 and ORF6 (Inamine et al., 1988b). In order to identify proteins translated from those ORFs, gene fusions between the N-terminus of the RNA replicase of the Escherichia coli bacteriophage MS2 and selected regions of ORF4 and ORF6 were constructed. The corresponding fusion proteins synthesized in Escherichia coli were used to immunize mice. Antisera directed against ORF4-related sequences did not recognize M. pneumoniae antigens in Western blot analysis, but antisera directed against ORF-6-derived fusion proteins reacted with two M. pneumoniae proteins of 40 kDa and 90 kDa. In addition, some of the antisera also recognized proteins that formed in a sodium dodecyl sulphate/polyacrylamide gel a protein ladder between 115 and 145 kDa. PMID- 1904125 TI - Molecular analysis of the methane monooxygenase (MMO) gene cluster of Methylosinus trichosporium OB3b. AB - The oxidation of methane to methanol in methanotrophic bacteria is catalysed by the enzyme methane monooxygenase (MM0). This multicomponent enzyme catalyses a range of oxidations including that of aliphatic and aromatic compounds and therefore has potential for commercial exploitation. This study details the molecular characterization of the soluble MMO (sMMO) genes from the Type II methanotroph Methylosinus trichosporium OB3b. The structural genes encoding the alpha, beta and gamma subunits of sMMO protein A and the structural gene encoding component B have been isolated and sequenced. These genes have been expressed and their products identified using an in vitro system. A comparative analysis of sMMO predicted sequences of M. trichosporium OB3b and the taxonomically related M. capsulatus (Bath) is also presented. PMID- 1904126 TI - Genetic analysis of superoxide dismutase, the 23 kilodalton antigen of Mycobacterium tuberculosis. AB - The gene encoding a 23 kilodalton protein antigen has been cloned from Mycobacterium tuberculosis by screening of a recombinant DNA library with monoclonal antibodies. The product of the gene has been identified as the superoxide dismutase (SOD) of M. tuberculosis on the basis of sequence comparison and by expression of the recombinant protein in a functionally active form. The derived amino acid sequence of M. tuberculosis SOD reveals a close similarity to manganese-containing SODs from other organisms, in spite of the fact that previous studies using the purified enzyme have identified iron as the preferred metal ion ligand. SOD is present in the extracellular fluid of logarithmic-phase cultures of M. tuberculosis, but the structural gene is not preceded by a signal peptide sequence. Insertion of the M. tuberculosis SOD gene into a novel shuttle vector demonstrated the mycobacteria but is ineffective in Escherichia coli. PMID- 1904127 TI - The secretion genes of Pseudomonas aeruginosa alkaline protease are functionally related to those of Erwinia chrysanthemi proteases and Escherichia coli alpha haemolysin. AB - The extracellular alkaline protease produced by Pseudomonas aeruginosa is secreted by a specific pathway, independent of the pathway used by most of the other extracellular proteins of this organism. Secretion of this protease is dependent on the presence of several genes located adjacent to the apr gene. Complementation studies have shown that PrtD, E, and F, the three secretion functions for Erwinia chrysanthemi proteases B and C (Letoffe et al., 1990), can mediate the secretion of the alkaline protease by Escherichia coli. The secretion functions involved in alpha-haemolysin secretion in E. coli (hlyB, hlyD, tolC) can also be used to complement alkaline protease secretion by E. coli, although less efficiently. These data indicate that protease secretion mechanisms in Pseudomonas and Erwinia are very similar and are homologous to that of E. coli alpha-haemolysin. PMID- 1904129 TI - Physical and genetic map of the Methanococcus voltae chromosome. AB - A physical map of the Methanococcus voltae chromosome was constructed on the basis of restriction mapping and cross-hybridization experiments, employing total and partial digests obtained with rarely cutting restriction enzymes. On the basis of the sum of the fragment sizes of digests with seven enzymes the chromosome length was calculated to be approximately 1900 kb. The derived map is circular. Hybridization of gene probes to mapped restriction fragments has led to a genetic map of genes for structural RNAs as well as proteins, including enzymes involved in the methanogenic pathway. PMID- 1904128 TI - Post-transcriptional control of a sporulation regulatory gene encoding transcription factor sigma H in Bacillus subtilis. AB - The transcriptional regulatory gene spoOH encodes an RNA polymerase sigma factor called sigma H that directs gene expression at an early stage of sporulation in the Gram-positive bacterium Bacillus subtilis. We now report that conditions that induce sporulation cause a rapid increase in the cellular concentration of sigma H. This increase could account for the stimulated transcription of certain sigma H-controlled genes at the onset of sporulation. Experiments in which the expression of spoOH was monitored by use of a spoOH-lacZ fusion and in which expression of spoOH was artificially manipulated by use of an isopropyl-beta-D thiogalacto-side-inducible promoter indicate that sporulation-induced increases in the amount of sigma H are not controlled at the level of the transcription of its structural gene. Rather, we infer the existence of post-transcriptional control mechanisms that govern sigma H levels, and we present evidence suggesting that increases in the amount of sigma H at the start of sporulation are due to increased translation or stability of the spoOH mRNA and, to a lesser extent, decreased turnover of spoOH protein. PMID- 1904130 TI - Precipitating factors in diabetic ketoacidosis. PMID- 1904131 TI - Tocainide therapy in muscle cramps and spasms due to neuromuscular disease. AB - Significant improvement in symptoms of disabling cramps and muscle spasms was obtained in 9 patients with motor neuron diseases, tetany, and myotonic disorders who were treated with tocainide, a lidocaine analog. No significant side effects were observed except for light-headedness and fatigue in 1 patient, who also showed slight prolongation of intraventricular conduction time. Tocainide is useful in treating disabling muscle spasms and cramps associated with conditions characterized by neuromuscular irritability. This effect is probably based on stabilization of the membrane potential at various levels (motor neurons, peripheral nerve, or muscle fiber membrane). PMID- 1904132 TI - Nephrotoxic potential of Bence Jones proteins. AB - BACKGROUND: The renal manifestations of diseases associated with the production of monoclonal light chains--myeloma (cast) nephropathy, light-chain deposition disease, and amyloidosis AL--result from the deposition of certain Bence Jones proteins as tubular casts, basement-membrane precipitates, or fibrils, respectively. For unknown reasons, the severity of the renal manifestations of these diseases varies greatly from patient to patient. We employed an experimental in vivo model to determine the pathologic importance of various Bence Jones proteins. METHODS: Mice were injected intraperitoneally with 300 mg of Bence Jones protein from 40 patients with multiple myeloma or amyloidosis AL and killed 48 hours later. The mouse kidneys were examined by light and electron microscopy, and light-chain deposits were identified immunohistochemically with highly specific antihuman light-chain antiserum. RESULTS: Of the 40 different human Bence Jones proteins studied, 26 were deposited in the mouse kidneys predominantly as tubular casts, basement-membrane precipitates, or crystals; no light-chain deposits were detected in the kidneys of the mice that received the other 14 Bence Jones proteins. Of the 18 patients for whom renal tissue was available for study, the findings in 14 were comparable to those in the mice. Furthermore, the proteins obtained from 22 of the 27 patients whose serum creatinine concentrations equaled or exceeded 168 mumol per liter (1.9 mg per deciliter) were deposited in the mouse kidneys, whereas protein deposition occurred after the injection of proteins from only 4 of the 13 patients with serum creatinine concentrations below 168 mumol per liter. The repeated injection of Bence Jones proteins from two patients who had amyloidosis AL resulted in deposition of the protein in the mouse kidneys as amyloid. CONCLUSIONS: Particular Bence Jones proteins are primarily responsible for producing the distinctive types of protein deposition in renal tissue and the clinical manifestations that occur in patients with light-chain-associated diseases. This experimental model has potential value for the identification of nephrotoxic or amyloidogenic light chains. PMID- 1904133 TI - Improvement by acetylcysteine of hemodynamics and oxygen transport in fulminant hepatic failure. AB - BACKGROUND: When administered early after an overdose of acetaminophen, intravenous acetylcysteine prevents hepatic necrosis by replenishing reduced stores of glutathione. How acetylcysteine improves the survival of patients with established liver damage induced by acetaminophen, however, is unknown. This study was undertaken to determine whether the beneficial effect of acetylcysteine under such circumstances could be due to enhancement of oxygen delivery and consumption. METHODS: We studied the effect of acetylcysteine on systemic hemodynamics and oxygen transport in 12 patients with acetaminophen-induced fulminant hepatic failure and 8 patients with acute liver failure from other causes. The acetylcysteine was given in a dose of 150 mg per kilogram of body weight in 250 ml of 5 percent dextrose over a period of 15 minutes and then in a dose of 50 mg per kilogram in 500 ml of 5 percent dextrose over a period of 4 hours; measurements were made before treatment began and after 30 minutes of the regimen. RESULTS: In the patients with acetaminophen-induced liver failure, the infusion of acetylcysteine resulted in an increase in mean oxygen delivery from 856 to 975 ml per minute per square meter of body-surface area (P = 0.0036), due to an increase in the cardiac index from 5.6 to 6.7 liters per minute per square meter (P = 0.0021). Mean arterial pressure rose from 88 to 95 mm Hg (P = 0.0054) despite a decrease in systemic vascular resistance from 1296 to 1113 dyn.sec.cm-5 per square meter (P = 0.027). There was an increase in oxygen consumption from 127 to 184 ml per minute per square meter (P = 0.0007) associated with an increase in the oxygen-extraction ratio from 16 to 21 percent (P = 0.022). The effects in the patients with acute liver failure from other causes were similar. CONCLUSIONS: The increase in oxygen delivery and consumption in response to acetylcysteine may account for its beneficial effect on survival in patients with fulminant hepatic failure induced by acetaminophen. PMID- 1904134 TI - Acute spinal-cord injury. PMID- 1904135 TI - Renal complications of B-cell dyscrasias. PMID- 1904136 TI - Public health. Hazards of risk assessment. PMID- 1904137 TI - Origin of AIDS. PMID- 1904138 TI - High levels of thyrotropin-releasing hormone precursor peptide immunoreactivity and binding substance occur in human cerebrospinal fluid. AB - A thyrotropin-releasing hormone (TRH) precursor peptide, pGlu-His-Pro-Gly (TRH Gly) and related peptides were measured in human cerebrospinal fluid (CSF) with a TRH-Gly radiommunoassay and the levels of immunoreactivity (IR) were found to be 136- to 352-fold higher than the corresponding levels of TRH-IR. TRH-IR levels in CSF are elevated during the active phase of multiple sclerosis (MS). We have used this TRH-Gly RIA to determine whether this TRH precursor peptide is also elevated in CSF from MS and Alzheimer's (ALZ) disease patients in comparison with the corresponding levels in non-central nervous system disease (control) patients. A highly significant increase in TRH-Gly-IR was observed in MS and ALZ CSF samples compared to control CSF. Cation exchange and exclusion chromatography of extracts of mixtures of CSF and synthetic TRH-Gly revealed two peaks of TRH-Gly-IR. One cochromatographed with synthetic TRH-Gly and the other was attributable to the formation of a complex between TRH-Gly and a binding substance originating in CSF. Corresponding studies with extracts of mixtures of CSF and synthetic TRH revealed no evidence for TRH binding with any component of CSF. Reverse-phase high-pressure liquid chromatography of pooled extracts of normal CSF revealed that about a third of the total TRH-Gly-IR coeluted with synthetic TRH-Gly. The half-time for in vitro metabolism of synthetic TRH-Gly in fresh CSF was 5 times longer than for synthetic TRH at 37 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1904139 TI - Detection of preclinical Parkinson's disease with PET. AB - Putamen 18F-dopa uptake of patients with Parkinson's disease (PD) is reduced by at least 35% at onset of symptoms; therefore, positron-emission tomography (PET) can be used to detect preclinical disease in clinically unaffected twins and relatives of patients with PD. Three out of 6 monozygotic and 2 out of 3 dizygotic unaffected PD co-twins have shown reduced putamen 18F-dopa uptake to date. In addition, an intact sibling and a daughter of 1 of 4 siblings with PD both had low putamen 18F-dopa uptake. These preliminary findings suggest there may be a familial component to the etiology of PD. PET can also be used to detect underlying nigral pathology in patients with isolated tremor and patients who become rigid taking dopamine-receptor blocking agents (DRBAs). Patients with familial essential tremor have normal, and those with isolated rest tremor have consistently low, putamen 18F-dopa uptake. Drug-induced parkinsonism is infrequently associated with underlying nigral pathology. PMID- 1904140 TI - Preclinical detection of Parkinson's disease: biochemical approaches. AB - Dysfunction of NADH: ubiquinone oxidoreductase (complex I) of the mitochondrial electron transport chain has been linked to the pathogenesis of Parkinson's disease. While simple assays of complex I activity are unlikely to be useful in the preclinical detection of Parkinson's disease, other more sophisticated physical-chemical approaches including detection of free radical damage may have utility. Leber's hereditary optic neuropathy may provide a useful model system for development of such strategies. PMID- 1904141 TI - Mitochondrial DNA and Parkinson's disease. AB - Two major lines of evidence support the hypothesis that an impairment of mitochondrial function may underlie neuronal death in Parkinson's disease. First, the neurotoxicity of the parkinsonism-inducing compound 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) is due to the generation of its 1-methyl-4 phenylpyridinium (MPP+) metabolite in the central nervous system; the toxicity of MPP+ is likely to result from its ability to block mitochondrial electron flow at the level of complex I. Second, recent studies have revealed a deficiency of mitochondrial complex I activity in the brain as well as other tissues of parkinsonian patients. This enzyme activity reduction might be explained by a defect in one or more of the genes coding for the subunits of complex I. Since seven of these genes are localized in the mitochondrial genome, it is conceivable that abnormal mitochondrial DNA (mtDNA) might play a role in the pathogenesis of Parkinson's disease. The entire sequence of the human mitochondrial genome is known, and human mtDNA can be isolated and rapidly analyzed using techniques such as the polymerase chain reaction. Therefore, identification of an easily detectable mtDNA alteration might ultimately be used as a marker for the diagnosis and screening of Parkinson's disease. PMID- 1904142 TI - [Our experience in diagnosis and surgical treatment of duodenal diverticula]. AB - In view of the proteiform symptoms of duodenal diverticula, the Authors underline the diagnostic precision and surgical value of e.g.d. scopy. Indications for surgery in cases of symptomatic or complicated diverticula are also stressed, and the value of mechanical suturing is confirmed. PMID- 1904143 TI - [Diverticula of the duodenum. Our experience in 27 cases]. AB - After the colon, the duodenum is the most common site of diverticula. The Authors describe their experience of the surgical treatment of 27 patients suffering from duodenal diverticulosis. Treatment of diverticula was associated with therapy for more severe underlying pathologies in 23 cases. Four cases underwent elective treatment for symptomatic diverticulosis. No major complications or increase in the average time spent in hospital were observed in either group. PMID- 1904144 TI - [Postoperative infections in otorhinolaryngologic surgery. Open study on efficacy and tolerability of antibiotic prophylactic treatment with sulbactam-ampicillin]. AB - The paper reports the results of an open study on the efficacy and tolerability of the association of sulbactam-ampicillin in antibiotic prophylaxis in ENT surgery. The study include 55 cases and confirmed both the total absence of major side-effects and a notable therapeutic efficacy of the drug in question. It is interesting to note the results obtained in ENT cancer surgery: out of 12 cases of partial or total laryngectomies there were 2 cases of infection in extra operative sites (polmoniti ab ingestis from Pseudomonas aeruginosa) and none within the site of operation. Data regarding the efficacy of the drug were in line or better than previously published results and its low toxicity indicates the elective use of sulbactam/ampicillin in ENT surgical prophylaxis. PMID- 1904145 TI - [Gastrointestinal hemorrhage from solitary diverticulum of the small intestine]. AB - A case of gastrointestinal bleeding in an 83 y.o. white female is reported. The source of bleeding was from a solitary jejunal diverticulum. The Authors discuss the clinical findings, the pathogenetic hypothesis, the diagnostic approach and the surgical therapy. PMID- 1904146 TI - [Diabetic ketoacidosis (169 episodes in 131 patients in the course of 10 years)]. AB - Diabetic patient material--presenting hyperglycaemic ketoacidotic episode- observed in Gyula and Szekszard County Hospitals in period 1980-89, was reviewed by authors. 131 patients were admitted with 169 ketoacidotic episodes (among them 23 patients had 62 recurrences). The mean age of patients were 49.4 years (14-84 years), duration of diabetes 9.5 years (from one month to 45 years). The common cause of diabetic ketoacidosis was respiratory (26 per cent) and enteral (35.5 per cent) infection. The consciousness of patients had shown close correlation with the increase of blood sugar and urea nitrogen level as well as with the decreasing of the pH value of capillary blood. The first step of the therapy was the parenteral fluid intake with isotonic solution (in the first hour the average 1351 ml). In 18 patients fast-acting insulin (Novo Actrapid MC) was given by constant infusion, in the remaining cases intravenous or intramuscular low doses of the same insulin were administered. The importance of early potassium replacement, and the dangers of forced and rapid correction of acidosis is emphasized. Lethality related to episodes was 10 per cent, related to the patients 12.9 per cent. The number of ketoacidotic cases did not decrease parallel with the improvement of therapeutic possibilities, as it was experienced by their earlier evaluations. The importance of the prevention of acute metabolic disorders is outlined might be resulted from increasing the efficacy of patients education and better knowledge of GP's, as well. PMID- 1904147 TI - Allocating health care resources: balancing the interests of the child and society. PMID- 1904148 TI - Nonanthrax Bacillus infections of the central nervous system. PMID- 1904149 TI - [Somnambulism in children]. PMID- 1904150 TI - Posterior hypothalamic modulation of the respiratory response to CO2 in cats. AB - Several studies have provided evidence that suprapontine structures are involved in modulating the respiratory response to increases in carbon dioxide. However, the actual neuroanatomical site(s) responsible for this effect has not been identified. Therefore, the purpose of the present study was to determine if the posterior hypothalamus is one rostral site involved in the modulation of the respiratory response to hypercapnia. Phrenic nerve responses to progressive step increases in end-tidal PCO2 were recorded before and after unilateral microinjection of gamma-aminobutyric acid (GABA) antagonists into the posterior hypothalamus of anesthetized cats, which were paralyzed and ventilated. Microinjection of the antagonists reduced the apneic threshold to lower values of end-tidal PCO2. In addition, phrenic nerve responses to changes in CO2 above the apneic threshold were augmented following microinjections of the GABA antagonists. This augmentation resulted from larger respiratory frequency responses with slight increases in the tidal phrenic response. Microinjection of a GABA agonist into the same hypothalamic site reversed the effects of the GABA antagonist. Microinjection of the GABA agonist without a preceding antagonist injection had no effects. These results suggest that the respiratory responses to increases in PCO2 above the apneic threshold are modulated by neurons in the posterior hypothalamus in anesthetized cats. This hypothalamic modulation involves a GABAergic mechanism. PMID- 1904151 TI - Isolation and identification of two new Synechococcus-derived restriction endonucleases, SleI and SspAI, isoschisomers of EcoRII. PMID- 1904152 TI - An estrogen-dependent polysomal protein binds to the 5' untranslated region of the chicken vitellogenin mRNA. AB - An estrogen-dependent protein present in chicken liver polysomes binds to the 5' untranslated region of the chicken vitellogenin II mRNA. Competition binding assays with different RNAs indicate that the binding of the polysomal protein to this region is sequence specific. Of the tissues tested, this RNA binding activity is liver specific. In vivo kinetics of appearance of the binding activity following a single injection of estrogen to immature chicks are similar to the rate of accumulation of vitellogenin mRNA. The molecular weight of the polysomal protein has been estimated to be 66,000 on the basis of UV crosslinking and subsequent SDS polyacrylamide gel electrophoresis. In vitro RNA decay assays carried out with a minivitellogenin mRNA suggest that the estrogen-dependent polysomal protein may be involved in the estrogen-mediated stabilization of the chicken vitellogenin II mRNA. PMID- 1904153 TI - Identification of the sequences recognized by phage phi 29 transcriptional activator: possible interaction between the activator and the RNA polymerase. AB - Expression of Bacillus subtilis phage phi 29 late genes requires the transcriptional activator protein p4. This activator binds to a region of the late A3 promoter spanning nucleotides -56 to -102 relative to the transcription start site, generating a strong bending Tin the DNA. In this work the target sequences recognized by protein p4 in the phage phi 29 late A3 promoter have been characterized. The binding of protein p4 to derivatives of the late A3 promoter harbouring deletions in the protein p4 binding site has been studied. When protein p4 recognition sequences were altered, the activator could only bind to the promoter in the presence of RNA polymerase. This strong cooperativity in the binding of protein p4 and RNA polymerase to the promoter suggests the presence of direct protein-protein contacts between them. PMID- 1904155 TI - Don't blame the institution. PMID- 1904154 TI - mRNA transcripts initiating within the human immunoglobulin mu heavy chain enhancer region contain a non-translatable exon and are extremely heterogeneous at the 5' end. AB - Transcription events are thought to precede gene rearrangement in the immunoglobulin (Ig) loci and may be the mechanism by which the various gene regions are made accessible for recombination. If this is the case, identification and characterization of transcripts from the Ig loci should permit a better understanding of the gene rearrangement process. We have isolated a 2.3 kb cDNA clone from the human pre-B cell line Nalm-1 that contains enhancer specific sequences from the Ig heavy (H) chain gene locus. The 2.3 kb transcript initiated within the enhancer region and showed extreme 5' heterogeneity, with more than 50 initiation sites mapping near the Ig-specific octamer ATTTGCGT. Sequencing of the cDNA clone demonstrated that 644 nucleotides from the Ig enhancer region were incorporated as a leader exon spliced to the mu constant (Cmu) region. This leader exon contained many translation termination codons and may function to inhibit the translation of sterile Cmu polypeptides. Using an enhancer-derived probe, we detected two low-abundancy mRNA transcripts with sizes of 2.3 and 12 kb. Northern blot analysis suggested that the 12 kb transcript was the unspliced precursor mRNA of a VDJ rearrangement. The potential role of these enhancer-containing transcripts in the opening of the IgH chain gene for rearrangement and for class switching is discussed. PMID- 1904156 TI - Medical audit and formulary management: a policy for rational use of thrombolytic drugs. AB - In this article we report on the development, introduction, and maintenance of a policy to promote rational use of thrombolytic drugs by hospital doctors. The work was undertaken within the framework of the voluntarily operated Riverside East drugs guide (formulary) management system (FMS). The policy was introduced in October 1988 and revised in November 1989 to coincide with the launch of the new, expensive thrombolytic drugs, alteplase (rt-PA, Actilyse) in 1988 and antistreplase (APSAC, Eminase) in 1989. Streptokinase was recommended as the first-line drug for patients who had not received it within the last 6 months. The policy was communicated to all staff in meetings and a drugs guide bulletin and reinforced by ward pharmacists. Results over a 15 month period show voluntary compliance by prescribers with the recommended policy. One hundred and seventy four patients (22% cardiac admissions) presented with acute myocardial infarction. Of these 43 (25%) received streptokinase, the first-line recommended drug, 7 received alteplase and none received anistreplase. The savings in drug expenditure from using streptokinase rather than alteplase or anistreplase for the 15-month period of investigation were over pounds 27,000. This work represents an example of the effectiveness of the Riverside East FMS model in influencing prescribing behaviour. PMID- 1904158 TI - [Explanatory notes on arthritis and purulent pericarditis as presentation form of sepsis caused by serogroup C meningococcus]. PMID- 1904157 TI - Severe diabetic retinopathy at presentation in a young man. AB - A 22 year old man presented with a severe ischaemic diabetic retinopathy and, in spite of photocoagulation therapy, was blind in one eye 16 months after diagnosis. Four similar cases of aggressive diabetic retinopathy are reviewed. There is increasing evidence that a small group of young men with insulin dependent diabetes (IDD) may develop severe diabetic retinopathy at, or soon after, diagnosis. PMID- 1904159 TI - [Ultrasensitive TSH and thyroliberin test in patients hospitalized for depression]. AB - In this prospective study of 35 patients hospitalized for depression, TSH levels were measured before and after stimulation by TRH. The type of depression was determined and its intensity was evaluated by means of the HARD scale. Subjects with systemic disease or receiving treatments known as being likely to influence TSH levels had been excluded. In none of these 35 patients was the TSH level below the lower limit of normal values, nor was there any blunting of response to TRH. These results suggest that depression is not a cause of TSH fall and that a low TSH level with normal hormonaemia must call for scintiscanning, even in depressed subjects. PMID- 1904160 TI - Invasive aspergillus rhinosinusitis in patients with acute leukemia. AB - Invasive aspergillus rhinosinusitis is a potentially lethal complication of chemotherapy-induced neutropenia in patients with acute leukemia. The majority of cases are caused by Aspergillus flavus. The infection is difficult to diagnose early but should be suspected when a neutropenic patient develops persistent fever without a known source, symptoms of rhinitis or sinusitis, cutaneous findings over the nose or sinuses, symptoms and signs of orbital or cavernous sinus disease, or an ulcerating lesion of the hard palate or gingiva. Careful anterior rhinoscopy followed by computed tomography of the sinus helps establish the diagnosis, which should be confirmed by histologic study and culture of biopsied material. Early treatment with aggressive surgery, high-dose amphotericin B and 5-fluorocytosine, and possibly white blood cell transfusions may produce a cure if the patient's bone marrow recovers. Newer antifungal agents offer promise for prophylaxis and treatment of this infection. PMID- 1904161 TI - Relationship between acute myelomonoblastic leukemia and infection due to human immunodeficiency virus. AB - Infection due to the human immunodeficiency virus (HIV) has been complicated by the development of acute nonlymphocytic leukemia in five patients whose cases have previously been reported; other manifestations, including preleukemia, myelofibrosis, and myeloid hyperplasia, have also been reported in patients infected with HIV. We report the sixth case of an HIV-infected patient who developed acute myelomonocytic leukemia; HIV infection was documented by tests for serum antibodies (enzyme-linked immunosorbent assay and western blotting), by a markedly elevated p24 antigen level in plasma, and by cultures of CSF and peripheral blood that were positive for HIV. Furthermore, myelomonoblasts that were cultured without the addition of growth factors displayed evidence of HIV replication through the presence of p24 antigen and reverse transcriptase activity, both of which lasted for 4 weeks in the supernatant fluid of the cell cultures. This case report provides the first data indicating that HIV may infect myelomonoblasts in vivo and represents the sixth reported case of an association between HIV infection and pure acute nonlymphocytic leukemia. PMID- 1904162 TI - [Lasers in plastic and reparative surgery]. PMID- 1904163 TI - [Protective effect of misoprostol on the changes of transgastric potential difference induced by aspirin in man]. AB - The measurement of transgastric electric potential difference (DDP) is an easy and reproducible method for evaluation of the gastrotoxicity of aspirin. This randomised crossover placebo-controlled trial in 12 healthy volunteers involved study of the protective effect of misoprostol (Cytotec) against the fall in DDP induced by a gram of aspirin. One day of treatment with misoprostol 200 micrograms morning and evening led to a statistically lower fall in DDP than with the placebo: area under the curve 130 +/- 315 mV.min cf. 589 +/- 465 mV.min (p = 0.012), maximum variation 11.4 +/- 11.3 mV cf. 24.9 +/- 13.2 mV (p = 0.04). This result independent of the antisecretory action of the compound, confirms the protective effect of this prostaglandin analogue against the gastric damage caused by aspirin. PMID- 1904164 TI - [Anti-retroviral therapy of HIV-infection. With preliminary results of the Swiss postmarketing surveillance of zidovudine]. AB - In the last few years, the treatment of HIV infection has advanced considerably due to the development of active antiretroviral compounds. Many substances with different mechanisms of action show strong activity against HIV in vitro and many of them are now under clinical investigation. But immense effort is needed to develop a clinically effective and tolerable drug for daily use from a substance active in vitro. Presently, zidovudine is the only drug that can be used for the treatment of HIV infection outside of clinical studies. The efficacy of zidovudine was demonstrated in patients with symptomatic HIV infection as well as in patients with advanced asymptomatic disease. The clinical signs of efficacy are significantly delayed progression of HIV infection and lower frequency of opportunistic infections, with decreased severity. It is evident that zidovudine does not cure the HIV infection. In Switzerland treatment with zidovudine is evaluated by post-marketing surveillance (PMS). All patients on zidovudine are seen periodically in the hospitals with a specialized division for HIV infection. Clinical and laboratory follow-ups are recorded. Until the beginning of October 1990, 1171 patients with symptomatic HIV infection have been treated with zidovudine in the setting of this PMS. 62% of all registered patients are currently receiving zidovudine. 20% died of AIDS. 15% of all patients received at least one blood transfusion. Hematotoxicity is the most frequent and serious side effect of zidovudine and can require definitive termination of therapy. The side effects are dose related and occur more severely in patients with advanced disease. The ideal dosage of zidovudine has not yet been defined. Recently published studies showed efficacy with doses as low as 500 mg/d. Consequently, patients in Switzerland receive 10 mg zidovudine/kg body weight as the maximum dose, divided into two or more single daily doses. Patients with asymptomatic HIV infection are regularly treated with 500 mg/d. Zidovudine-intolerant patients with symptomatic HIV infection can currently enter a controlled clinical trial of antiretroviral therapy with dideoxyinosine (ddI), which has a different spectrum of side effects but is only minimally toxic to bone marrow. PMID- 1904166 TI - [Radiological diagnosis of benign dysphagia]. AB - In the diagnostic work-up of the benign dysphagia modern radiology must not only describe morphologic alterations but also has to keep in mind the great importance of motility disorders. Dysfunction of the esophagus can be assessed by fluoroscopy alone. The superior method to analyze the motility disorders of the oropharyngeal and pharyngo-esophageal transport is high-speed cineradiography at a frame-rate of 50 frames/sec on 35-mm film because of the very fast and complex patterns of motion during oropharyngeal deglutition, which occurs within only 0.5 to 0.7 sec. The upper esophageal sphincter turned out to play a very important role in many motility disorders of the pharynx and the esophagus, which often secondarily leads to permanent structural lesions. Examples are given, in which kinds of disorders cineradiography contributes to diagnosis and therapy. In some cases it turned out to be the method of first choice, as for example for aspiration. PMID- 1904165 TI - Early local experience of ankle arthrography and its influence on management of patients with ankle injury. AB - Ankle arthrography was performed on 64 patients with a history of ankle injury from 21 January 1986 to 11 October 1988. There was a male predominance in the ratio of 15 to 1 and the mean age of our patients was 22 years. A total of 65 arthrograms were obtained as one patient had bilateral ankle arthrograms. Of these, 29 arthrograms were normal. A year after completing this study, we attempted to retrieve our patients' case-notes and reviewed their subsequent management. Our results showed that multiple factors influenced the further management of our patients and arthrogram did play a role in this respect. PMID- 1904167 TI - [Nasal and paranasal sinus surgery. 217 patients treated with endoscopic surgical techniques]. AB - We present an evaluation of our first 217 patients following introduction of functional endoscopic surgery. CT-examination of the paranasal sinuses, together with diagnostic nasoscopy, have greatly improved diagnostic accuracy in sino nasal diseases. Reestablishment of normal mucociliary drainage is a prerequisite for successful surgery. The majority of patients suffered from nasal polyposis and sinusitis. Drainage of mucoceles and subperiostal orbital abscesses have been performed, as well as resection of bullous middle turbinates. Functional endoscopic nasal surgery reduces morbidity from surgery and therefore, compared with earlier surgical methods, is more cost-effective health economy. PMID- 1904168 TI - [Extracorporeal membrane oxygenation. A therapeutic alternative in acute heart and/or pulmonary failure?]. AB - Extracorporeal membrane oxygenation was introduced as a supplement ot mechanical ventilation in the treatment of two patients with severe acute respiratory failure and as heart assist in one patient with acute refractory cardiac failure after open heart surgery. The system includes a membrane oxygenator and a roller pump. The whole circuit is coated with partially degraded heparin covalently bound to the surface (Carmeda Bioactive Surface), reducing the need of systemic heparinization to a minimum. In the first case of acute respiratory failure a veno-venous bypass was employed, with cannulas in the right atrium and the femoral vein. Given a blood flow through the circuit of 2.5 l/min, ventilator settings could be favourably reduced. The patient was weaned off the bypass system after six days, off the ventilator after 120 days, and recovered completely. In two cases the system served as partial venoarterial bypass, and blood was returned to the ascending aorta. A 31 year-old male victim of a smoke inhalation lung injury was on bypass for four and a half days. He recovered completely after another 17 days of mechanical ventilation. A 68 year-old man with pump failure after cardiac surgery needed extracorporeal support as heart assist for seven days. On the eighth day he was weaned off intra-aortic balloon pumping as well. Unfortunately, he died of septicemia, with multiple organ failure, 13 days later. The heparin-coated extracorporeal membrane oxygenation system may represent a major advancement in the treatment of critically ill patients in need of cardiopulmonary assist. PMID- 1904169 TI - Changes in the levels of protein and steroid hormones in the plasma and steroid hormone receptors in the uterus of normal cycling guinea pigs. AB - This study deals with the estrous cycle of guinea pigs in relation to sexual behavior, uterine weight, levels of gonadotropins, steroid hormones, and steroid hormone receptors in the uterus. The guinea pigs in this study showed cyclic changes in various reproductive functions broadly similar to other laboratory species studied. The increase in the uterine weight coincided with high concentration of steroid hormones (estradiol and progesterone) secreted during proestrus and estrus. The elevated levels of steroid hormone receptor concentrations in the uterus during these periods also confirm the role of these hormones. The rise in progesterone level from day 14 of the cycle was associated with lordosis and its related behavior. It was noted that the "estrus behavior" is the most accurate external marker for ovulation and sexual receptivity to males. It was also observed that there is an association between follicle stimulating hormone and luteinizing hormone during the preovulatory period that was not demonstrated in previous studies. PMID- 1904170 TI - [Protective measures in a psychogeriatric nursing home]. AB - In a psychogeriatric nursing home with 252 patients, the policy concerned with so called protective measures was investigated. Protective measures, like physical restraints, guard patients, who are mentally incapable, from physical injury. In 69.1% of the patients one or more protective measures were applied. For most of the patients this was a daily application for a period of at least three months. One hundred and ten patients (43.6%) were continuously exposed, during 24 hours a day, to several protective measures. It is concluded that this policy does not satisfy the official Dutch Governmental requirements for the quality of mental health care. Factors that cause the use of protective measures are discussed. PMID- 1904171 TI - Stone formation in substitution cystoplasty. PMID- 1904172 TI - Induction of anesthesia with diazepam-ketamine and midazolam-ketamine in greyhounds. AB - Anesthesia was induced in 14 greyhounds with a mixture of diazepam or midazolam (0.28 mg/kg) and ketamine (5.5 mg/kg), and maintained with halothane. There were no significant differences in weight, age, or duration of anesthesia between the treatment groups. Time to intubation with diazepam-ketamine (4.07 +/- 1.43 min) was significantly longer than with midazolam-ketamine (2.73 +/- 0.84 min). Heart rate, respiratory rate, PaCO2, and arterial pH did not vary significantly during anesthesia in either treatment group. Arterial blood pressures, PaO2, halothane vaporizer setting, and body temperature changed significantly from baseline values in both treatment groups during anesthesia. Times to sternal recumbency and times to standing were not significantly different. These data suggest that both diazepam-ketamine and midazolam-ketamine are useful anesthetic combinations in greyhounds. In combination with ketamine, midazolam offers little advantage over diazepam. PMID- 1904173 TI - Treatment of low arterial oxygen tension in anesthetized horses with clenbuterol. AB - Clenbuterol (0.8 microgram/kg intravenously) was administered to 10 anesthetized horses with an abnormally low PaO2 (less than 90 mm Hg) despite controlled ventilation with an oxygen-rich gas mixture. Results were compared with those from 10 controls to which no clenbuterol was given and in which conventional methods to increase PaO2 were ongoing. Horses treated with clenbuterol had higher PaO2 values for at least 90 minutes. Clenbuterol was associated with increased heart rate and profuse sweating. Clenbuterol can be administered intravenously to increase the PaO2 of mechanically ventilated horses that have low arterial oxygen tension while under inhalation anesthesia. Further studies are warranted to define more precisely the circumstances under which clenbuterol may be used safely. PMID- 1904174 TI - [Colloid-oncotic pressure in patients with diffuse suppurative peritonitis]. AB - 35 patients with various phases of generalized purulent peritonitis were tested. The goals of this study were to define the colloid-oncotic pressure (COP) and the contents of its main ingredient--albumin, determine the significance of the COP studies for the diagnosis of edema of lungs in cases of purulent peritonitis, and the influence of fluid management and parenteral nutrition upon the COP index. The studies have shown a clear dependency of COP and albumin ratio upon the phase of peritonitis. The authors come to a conclusion that the definition of COP dynamics is one of the most reliable criteria that makes it possible to chart a correct program of fluid management and reduce the number of postinfusional complications. PMID- 1904175 TI - [Energy expenditure in ENT-oncological patients: effects on disease and nutrition]. PMID- 1904176 TI - [Study of enzymes of xenobiotic metabolism in the evaluation of quality of protein-containing wheat germ flakes and wallpaper flour]. AB - Intake of wheat upholstery meal by growing rats was attended by a sharp decrease in the content and activity of xenobiotic metabolism enzymes in the hepatic microsomes, that was caused by the low biological value of the meal proteins. Hepatic microsomes of the rats that were fed with wheat germ flakes showed increased specific content of cytochromes P-450 and b5, but the total blood protein content per 100 g of body mass was lower than during casein consumption. No significant changes were detected in hydroxylation rate of benz(a)pyrene, aniline and ethylmorphine. During consumption of wheat germ flakes induction of UDP-glucuronide-transferase was detected in hepatic microsomes. Wheat germ flakes induced a 5-fold increase of Se-dependent glutathione peroxidase activity. Wheat germ flakes produced no significant effect on glutathione-S-aryltransferase and glutathione reductase activity. PMID- 1904177 TI - [Role of manometry in evaluating long-term outcomes of the surgical treatment of functional esophageal diseases]. AB - In the years 1979-1986, 73 patients with esophageal achalasia, 110 patients with the reflux disease of esophagus and paraesophageal herniae, 17 patients with esophageal diverticles and 33 patients with duodenal ulcer were examined. The patients were examined before the intervention and controlled repeatedly after the operation in the intervals up to one month, after 3-12 months and after 2-7 years. The contribution of manometry is considered to be in giving more precision to the diagnosis and, particularly in esophagocardial achalasia, in determining a suitable operation tactics. In the reflux disease of esophagus it can contribute to the decision between a conservative and surgical therapy. The postoperative control examinations help to make an exact evaluation of the results of operation in a complex with other methods of examination. PMID- 1904178 TI - [Esophageal diverticula. Clinical aspects and therapy]. AB - 18 patients (10 male, 8 female) with an average age of 57 years were operated for diverticula of the esophagus. We found 11 pharyngoesophageal diverticula, 5 parabronchial and 2 epiphrenic diverticula. Major symptoms were dysphagia and regurgitation in pharyngoesophageal diverticula. Dysphagia, substernal pain and hiccough in parabronchial and epiphrenic diverticula. The treatment was resection of diverticula which was combined with myotomy in case of pharyngoesophageal diverticula. 2 patients had severe secondary wound healing. Other postoperative dysfunctions of the esophagus or symptomatic recurrences were not seen. PMID- 1904179 TI - Fine needle aspiration biopsy diagnosis of tuberculous lymphadenitis in patients with and without the acquired immune deficiency syndrome. AB - All Bellevue Hospital cases from a recent 27-month period whose fine needle aspiration (FNA) samples of cervical or supraclavicular masses showed acute and/or granulomatous inflammation were reviewed. The 30 patients included 8 with the acquired immune deficiency syndrome (AIDS), 3 with the AIDS-related complex (ARC), 2 with AIDS risk factors and 17 without known risk factors for AIDS. Of these, mycobacterial infections had been diagnosed in 22 patients: 18 by cultures positive for Mycobacterium tuberculosis and 4 by positive staining for acid-fast bacilli. In addition to the presence of neutrophils, two criteria for the diagnosis of mycobacterial infection were identified on the routinely stained FNA smears: caseous material and granulomas. Caseous material was the most sensitive and specific criterion. Granulomas were often present in patients with mycobacterial infection, but were also occasionally present in patients with other processes. The differences in cytologic specimens between AIDS and non-AIDS patients are discussed. The findings suggest that FNA is a safe and sensitive technique for the diagnosis of mycobacterial lymphadenitis in AIDS patients and that purulent aspirates from appropriate patient populations should prompt the use of special stains and cultures to rule out mycobacterial infection. PMID- 1904180 TI - Recombinant alpha-interferons, thyroid irradiation and thyroid disease. AB - Recombinant alpha-interferons are used as therapeutic agents in an increasing number of benign and malignant disorders. Long-term administration of recombinant alpha-interferon as a maintenance agent is associated with a small number of adverse side-effects which are responsible for patient intolerance of this drug. These include weight loss, alopecia and chronic fatigue, anorexia and depression syndrome. This latter syndrome needs to be distinguished from thyroid disease, which is documented in this report in a number of patients on recombinant alpha interferon therapy. PMID- 1904181 TI - Pseudo-nonsecretory multiple myeloma with light chain deposition disease. AB - A diagnosis of nonsecretory myeloma was established in two patients with anemia and proteinuria on the basis of the suppression of polyclonal immunoglobulins and the increase of plasma cells in the bone marrow. No paraprotein was detected in the serum or concentrated urine of these patients. However, a plaque-forming assay of bone marrow cells showed the secretion of monoclonal immunoglobulin by the myeloma cells. Moreover, renal biopsies from both patients indicated the deposition of monoclonal light chains in the glomerular mesangium and basement membrane, as well as in the tubular basement membrane, a pattern consistent with light-chain deposition disease. These observations suggested that the secreted paraprotein disappeared rapidly as a result of enhanced catabolism or deposition in organs such as the kidney, producing severe proteinuria and chronic renal failure. The plaque-forming assay is a useful technique for the demonstration of this type of nonsecretory myeloma, pseudo-nonsecretory myeloma. PMID- 1904182 TI - Heterotopic bone formation following hip arthroplasty. A retrospective study of 65 bilateral cases. AB - Heterotopic bone formation after two-stage bilateral cemented total hip arthroplasty was evaluated in 65 patients (23 women and 42 men) who had not received treatment with antiinflammatory drugs in the immediate postoperative weeks. The mean age at the first operation was 65 years, and the median interval between the two arthroplasties was 3 months. Fifty-two patients developed heterotopic ossification after the initial hip arthroplasty. Of these patients, 40 also developed ossifications after contralateral hip arthroplasty. Out of 11 males developing Grade-III heterotopic ossification after the initial hip arthroplasty, 8 also developed Grade-III ossification after contralateral hip arthroplasty. Two females developed Grade-III ossification after the initial arthroplasty, but neither of them developed a Grade-III lesion after contralateral total hip arthroplasty. Males with Grade-III heterotopic ossification after the initial hip arthroplasty were shown to be at a high risk of developing the same severe lesion after contralateral total hip arthroplasty, making them candidates for postoperative prophylaxis. PMID- 1904183 TI - Naproxen prevention of heterotopic ossification after hip arthroplasty. A prospective control study of 55 patients. AB - The effect of naproxen on heterotopic ossification after total hip replacement was studied in a randomized, double-blind trial. Twenty-eight patients received 250 mg naproxen thrice daily for 4 weeks postoperatively starting on the morning of the operation while 27 control patients received a placebo. Three months after the operation, 13 patients in the control group had heterotopic ossification compared with 4 patients in the group that received naproxen; and after 1 year, the figures were 15 and 4, respectively (P less than 0.01). Three control patients had severe ossifications. We conclude that naproxen given for 4 weeks is sufficient to decrease the incidence of heterotopic ossification after cemented total hip replacement. PMID- 1904184 TI - Morphostereometry of heterotopic ossicles in the rat. AB - The objective of this study was to describe induced heterotopic bone formation in the rat using stereologic methods and to optimize the sampling for toxicologic studies. Bone formation was induced by implants of demineralized bone powder in 24 male Wistar rats. The ossicles formed were removed after 14, 16, 17, 18, and 20 days. From each ossicle, six sections were sampled equidistantly, and seven microscopic fields were analyzed in each section. Ossicle volume and weight decreased from Day 16 to Day 20. Bone volume density increased during the experimental period because of the reduction in ossicle volume, whereas the total bone volume did not change. Bone thickness increased from Day 14 to Day 20. No changes were observed in the surface density and total area of formative surfaces. The major part of the total variation was due to true variation between animals. The described histomorphometric methods may prove useful in quantitative toxicologic studies, e.g., of fluoride effects on cartilage and bone formation. PMID- 1904185 TI - Resorption of intraarticular diffusible and microcolloid tracers. Rabbit studies of normal and synovitic knees. AB - The resorption of two radiotracers (99mtechnetium-labeled microcolloid particles to study lymphatic transport and 51 chromium-EDTA to study diffusion) from the knee joint and the subcutaneous tissue of rabbits was investigated simultaneously. In 12 rabbits, synovitis was induced in the right knee 6 weeks or 3 months before the investigation; 6 rabbits served as controls. The final number of Tc-particles in the normal knees and in the subcutaneous tissue in the three groups did not differ; but removal from the synovitic knees was increased. The final number of Cr-EDTA particles did not differ within or between groups. The initial decrease was highest in the knees with acute synovitis (P less than 0.05). The results indicate (1) that in synovial tissue lymphatic transport is of little importance, (2) that leakage through the synovial membrane increases in synovitis, and (3) that a subcutaneous depot can be used as a reference instead of injections into a normal knee. PMID- 1904186 TI - Scrotal hyperthermia: frequency in an infertile population and associated alterations in testicular function. PMID- 1904187 TI - Bupropion. PMID- 1904188 TI - Etidronate for hypercalcemia of malignancy and osteoporosis. AB - The biphosphonates are becoming well established as effective agents for the treatment of metabolic bone diseases. Etidronate disodium is the only biphosphonate approved by the U.S. Food and Drug Administration. Accepted indications for etidronate therapy are symptomatic Paget's disease, heterotopic ossification and hypercalcemia of malignancy. An unapproved, but apparently successful use is treatment of postmenopausal osteoporosis. Both oral and intravenous preparations are available. Newer biphosphonates, which may be more efficacious and less toxic than etidronate, are being studied. PMID- 1904189 TI - Long-term effect of thrombolytic therapy on left ventricular ejection fraction after acute myocardial infarction. AB - To assess the long-term effect of thrombolytic therapy on left ventricular (LV) systolic function, 222 patients with acute myocardial infarction treated with intravenous tissue plasminogen activator within 4 hours of symptom onset underwent assessment of LV ejection fraction (EF) by radionuclide equilibrium angiography at hospital discharge and 1 year later. Mean EF at hospital discharge (46 +/- 12) was similar to that at 1 year (45 +/- 13). Stepwise multivariate linear regression analysis identified EF at discharge and patency of the infarct related artery before discharge as independent predictors of EF change at 1 year (p = 0.0002 and 0.003, respectively). Random assignments to invasive versus conservative treatment strategies or to early versus delayed beta-blocker therapy did not affect EF change during follow-up. No significant deterioration of EF was observed in patients with larger infarcts. However, EF decreased from 45 +/- 10 at hospital discharge to 39 +/- 12 (p = 0.005) at 1-year follow-up in a subgroup of patients with history of prior infarction. Thus, patients with acute myocardial infarction, treated with intravenous tissue plasminogen activator early after onset of symptoms, appear to have stable LV function between hospital discharge and 1 year follow-up. The change in EF between hospital discharge and 1 year can be predicted from the EF value at discharge, patency of the infarct related artery before discharge and history of previous myocardial infarction. PMID- 1904190 TI - Intracellular compartmentation of cardiac troponin T and its release kinetics in patients with reperfused and nonreperfused myocardial infarction. AB - In a previous study on the diagnostic efficiency of troponin T measurements in patients with suspected acute myocardial infarction (AMI), the authors found a high variability of troponin T serum concentration changes on day 1 in patients with AMI who underwent thrombolytic treatment. Therefore, the aims of the present study were to investigate the intracellular compartmentation of troponin T and to analyze the effects of AMI reperfusion on the appearance kinetics of cardiac troponin T in serum. Cardiac troponin T was measured with a newly developed bideterminant sandwich assay using cardiospecific, affinity-purified polyclonal antibodies and peroxidase-labeled monoclonal antibody. An unbound cytosolic troponin T pool was found in ultracentrifuged homogenates of myocardial tissue of different species ranging from 0.013 to 0.036 mg/g wet weight. The soluble troponin T molecule had electrophoretic properties identical to troponin T compartmented in the myofibrils. The clinical study group comprised 57 patients with AMI undergoing thrombolytic treatment. Blood flow to the infarct zone and point of time of reperfusion were tested by immediate and late angiography. The appearance of troponin T in serum on day 1 after the onset of AMI depended strongly on reperfusion and on duration of ischemia before reperfusion. Thus, in patients with early reperfused AMI, a marked peak in troponin T serum concentrations was found at 14 hours after the onset of pain. This early troponin T peak was absent in patients with AMI reperfusion occurring greater than 5.5 hours after the onset of pain and in patients with nonreperfused AMI. By contrast, the kinetics of troponin T release after the first day after AMI were unaffected by reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1904191 TI - Redoing the health care quilt. Patches or whole cloth? PMID- 1904192 TI - Pulmonary dysfunction in advanced liver disease: frequent occurrence of an abnormal diffusing capacity. AB - PURPOSE: Abnormalities in pulmonary function have been reported in association with chronic liver disease of varied etiology. The aim of this study was to better define the frequency and nature of these abnormalities in patients who were being evaluated for liver transplantation. PATIENTS AND METHODS: We performed a battery of pulmonary function tests and chest radiographs in 116 consecutive patients (50 men, 66 women; aged 19 to 70 years, mean 44.6 years) with severe advanced liver disease who were hospitalized specifically for evaluation for possible orthotopic liver transplantation and were able to perform technically satisfactory tests. In 17 patients, quantitative whole-body technetium-99m macroaggregated albumin perfusion scanning was also performed for assessment of possible right-to-left shunting through intrapulmonary vascular dilatations. RESULTS: The most commonly affected test of lung function was the single-breath diffusing capacity for carbon monoxide (DLCO), which was abnormal in 48%, 45%, and 71% of patients who never smoked, former smokers, and current smokers, respectively. Ventilatory restriction was noted in 25% of all patients, airflow obstruction (reduced ratio of forced expiratory volume in 1 second to forced vital expiratory volume in 1 second to forced vital capacity) in only 3%, and a widened alveolar-arterial oxygen gradient in 45%. Diffusion impairment was accompanied by a restrictive defect in only 35% of the patients and by an abnormally widened alveolar-arterial oxygen gradient in 60%. When diffusion impairment was accompanied by an oxygenation defect, it was also associated with a significantly increased right-to-left shunt fraction (mean 24.9%) assessed from quantitative whole-body perfusion imaging. On the other hand, isolated diffusion impairment unaccompanied by significant hypoxemia (noted in approximately a third of the patients with a reduced DLCO) was not associated with evidence of significant intrapulmonary shunting (mean right-to-left shunt fraction 6.7%). CONCLUSIONS: Most patients with advanced liver disease have one or more types of abnormality in lung function, a reduced DLCO being the single most common functional defect. Mechanisms accounting for the abnormality in gas transfer may include intrapulmonary vascular dilatations, diffuse interstitial lung disease, pulmonary vaso-occlusive disease, and/or ventilation-perfusion imbalance. PMID- 1904193 TI - Leukocytoclastic vasculitis associated with hepatitis C. PMID- 1904195 TI - Rosette formation by Plasmodium coatneyi-infected red blood cells. AB - Animal models are needed for the study of cytoadherence in falciparum malaria. Red blood cell (RBC) rosette formation is one type of cytoadherence and appears to be associated with knob formation, endothelial cell adhesion and sequestration of Plasmodium-infected RBCs. Since Plasmodium coatneyi-infected RBCs develop knobs and sequester, we hypothesized that they also form rosettes. RBCs from P. coatneyi-infected rhesus monkeys (Macaca-mulatta) were collected, allowed to mature overnight in vitro and found to form rosettes as hypothesized. This observation adds to the known falciparum-like characteristics of P. coatneyi, and suggests that the Macaca mulatta-P. coatneyi model may be appropriate for pathophysiologic studies of cytoadherence. PMID- 1904194 TI - Analysis of immunological characteristics of newly isolated strains of Rickettsia tsutsugamushi using monoclonal antibodies. AB - Since 1975, there has been an increase in the number of patients with tsutsugamushi disease in Japan, and marked antigenic heterogeneity has been found among newly isolated strains of Rickettsia tsutsugamushi. For antigenic analysis of these strains, we produced monoclonal antibodies against the Irie strain isolated in 1971, and the Hirano and Shimokoshi strains isolated in 1980. In all, 34 monoclonal antibodies were produced and their reactivities were determined by the immunofluorescent antibody test. The serological reactivity of the antibodies against these three strains and classic representative strains (Gilliam, Karp and Kato) showed varied reactive characteristics, i.e., serotype-specific, species specific and intermediate reactivities. It was revealed that these strains are antigenically different from the classic ones. Moreover, by using the serotype specific monoclonal antibodies, nine strains newly isolated in Miyazaki Prefecture were classified into the Irie and the Hirano types. The antigenicity of the Shimokoshi strain differed from those of the other strains used in this study. From these results, the strains of R. tsutsugamushi used in this study fell into six serotypes including the classic strains. SDS-PAGE and immunoblotting were performed to determine the molecular sizes of the antigenic polypeptides. The results revealed that the serotype-specific antigens belong to the 60-kDa class whereas the species-specific antigens belong to the 61-kDa, 60 kDa or 44-kDa class. PMID- 1904196 TI - Immunogenetic susceptibility for post-schistosomal hepatic fibrosis. AB - In 19 children with hepatic fibrosis as the result of continued schistosomiasis mansoni and 20 children without hepatic fibrosis, the following studies were carried out: HLA antigen typing for 30 antigens, immune response of T lymphocytes to schistosome antigen by measuring DNA synthesis evidenced by 3H-thymidine uptake, and measurement of total OKT3+, OKT4+, and OKT8+ cells using monoclonal antibodies. Patients with hepatic fibrosis were mostly high responders in contrast with those without fibrosis. High immune response and susceptibility to post-schistosomal hepatic fibrosis were associated with a high frequency of A2 and B12 antigens and a lack of DR2 antigens, while low response was associated with the presence of the DR2 antigen. The T4+:T8+ ratio showed increased suppressor proportions in patients with low immune response and/or with no hepatic fibrosis. We suggest an immunogenetic susceptibility for post schistosomal hepatic fibrosis, probably controlled by HLA-linked genes via the suppressor T cells. PMID- 1904197 TI - Granulomatous hypersensitivity to Schistosoma mansoni egg antigens in human schistosomiasis. III. In vitro granuloma modulation induced by immune complexes. AB - Granulomatous hypersensitivity to parasite eggs of Schistosoma mansoni is an important factor in the development of morbidity in chronic schistosomiasis. It has been demonstrated previously that the chronic, well-tolerated, intestinal form of schistosomiasis is associated with the establishment and maintenance of a variety of immunoregulatory mechanisms. We have used an in vitro model of granuloma formation for the purpose of studying the regulation of granulomatous hypersensitivity to S. mansoni egg antigens, mediated by immune complexes (IC). Our results show that the peripheral blood mononuclear cells (PBMCs) from patients with active schistosome infections, when treated with sera from chronic schistosomiasis patients, were able to induce an inhibitory activity on in vitro granuloma formation. Significant modulation of the in vitro granuloma reaction remained after treatment of PBMCs with isolated IC or manufactured IC with soluble egg antigen (SEA) and purified IgG from pooled chronic schistosomiasis sera. In contrast to granuloma modulation stimulated with whole molecule IgG-SEA IC, the incubation of PBMCs with F(ab')2 IgG-SEA IC did not induce any suppression of the granulomatous hypersensitivity to SEA. It appears in this model system that IC may inhibit the activity of granuloma formation by stimulating macrophages to release suppressive mediators. We have demonstrated this possibility by inhibition of prostaglandin activity using indomethacin. The addition of indomethacin to the granuloma culture significantly reduced in vitro granulomatous hypersensitivity to S. mansoni eggs in patients with chronic intestinal schistosomiasis and do so by inducing macrophages to secrete prostaglandins. PMID- 1904198 TI - Ultrasonographical investigation of periportal fibrosis in children with Schistosoma mansoni infection: reversibility of morbidity seven months after treatment with praziquantel. AB - Five hundred thirty six Sudanese schoolchildren with Schistosoma mansoni infection were treated at random with either 20 mg or 40 mg/kg praziquantel. Seven months later 420 children could be reinvestigated by ultrasonography. Reduction of egg excretion and reversibility of sonographically-proven periportal fibrosis (PF) was not significantly different in the two groups. Schistosoma mansoni-induced PF grade II decreased from 22.9% to 6.7% and grade III from 5.2% to 1.6%. An increased prevalence of PF grade I, from 10% to 29.8% of the investigated patients, was observed. This increase was caused partly by a downshifting of patients who had PF II (n = 45) and PF III (n = 8) before therapy, but also by patients who developed PF I in the seven months after therapy (n = 56). The overall percentage of patients with PF before and after treatment was 38.1%. Of 420 children, 17.4% increased in their PF grade, 55% remained at the same level and 27.6% improved. Children younger than 11 years of age had a higher rate of complete reversibility than older ones. The percentage of patients with hepatomegaly decreased significantly (11.6% to 6.9%; p = 0.001). The rate of splenomegaly remained unchanged. It was concluded that within seven months therapy with praziquantel resulted in a considerable qualitative improvement of PF in Sudanese schoolchildren with S. mansoni infection. PMID- 1904199 TI - Prolonged hypofibrinogenemia and protein C activation after envenoming by Echis carinatus sochureki. AB - Following envenomization by Echis carinatus sochureki, a professional snake handler developed a profound coagulopathy manifested by hemorrhage from the bite site, venipuncture sites and gums; coagulation testing revealed prothrombin and partial thromboplastin times greater than 150 seconds, a fibrinogen of 0 mg%, and marked elevation of fibrin degradation products. In addition, protein C antigen levels were undetectable. The coagulopathy was treated with cryoprecipitate; two different antivenoms were also administered with uncertain benefit. Subsequently, the properties of the venom and antivenoms were studied. Venom did not directly clot fibrinogen; however, venom concentrations as low as 0.2 micrograms/ml caused significant prothrombin activation. In addition, venom activated protein C in the absence of thrombomodulin, and this activity was inhibited by hirudin. The ability of four commercial antivenoms to neutralize the venom prothrombinase and hemorrhagic activity was measured. Three of the four antivenoms partially neutralized venom-induced prothrombin activation. Extreme differences in efficacy were found among the four antivenoms in neutralizing venom hemorrhagic activity in mice. This case illustrates the difficulty in managing the complex coagulopathy that can result from exotic snake envenomization, and identifies a new coagulant property of Echis carinatus venom (protein C activation). PMID- 1904200 TI - Genetic control of immunopathology induced by Mycobacterium leprae. AB - The pathogenesis of leprosy is almost totally attributable to the immune response of the host towards Mycobacterium leprae, a virtually non-toxic intra-cellular parasite. At one end of the leprosy spectrum are tuberculoid leprosy patients, who develop immunity but also delayed-type hypersensitivity towards M. leprae; at the other end are lepromatous leprosy patients, who lack helper T cell activity and therefore do not develop immunity, but who can nevertheless produce antibodies that may cause immunopathology due to immune complexes. A range of immunopathology is seen between these poles. PMID- 1904201 TI - Genetics of leprosy. PMID- 1904202 TI - Characterization of glycosphingolipids by supercritical fluid chromatography-mass spectrometry. AB - Gangliosides have been characterized by supercritical fluid chromatography chemical ionization mass spectrometry (SFC-CIMS) as permethyl and pertrimethylsilyl derivatives, using carbon dioxide as the SFC mobile phase and CI reagent gas. Ganglioside classes and ceramide heterogeneity within each class are well resolved by SFC. Direct SFC-interfacing allows the analytical manipulations of single-ion monitoring, total-ion plots, background subtraction, library searches, and spectral reconstruction algorithms. Addition of ammonia to the CI ion chamber (NH3 as a CI reagent gas) yields abundant molecular-weight related ions, (MH)+ and (MNH4)+ from analyte derivatives. Substitution of methanol for ammonia yields considerable parent-ion fragmentation, providing structural information on carbohydrate sequence, fatty acid, and sphingoid components. Under these latter conditions a unique alpha-cleavage fragment is observed which differentiates fatty acid from sphingosine heterogeneity. For ganglioside samples, the carboxyl group of neuraminyl residue(s) have been esterified with pentafluorobenzyl bromide and the products analyzed by negative ion chemical ionization MS. This modification improves chemical selectivity and greatly enhances detecting sensitivity. These "soft" ionization conditions provide abundant molecular-weight-related anions for collision-induced dissociation and subpicogram detection. PMID- 1904203 TI - Use of a voltage-responsive timer to quantitate hydroperoxides by the cyclooxygenase activation assay. AB - The importance of lipid hydroperoxides in the interpretations of physiological and pathological processes requires a valid and reliable microanalytical procedure. However, quantitation of the small amounts of lipid hydroperoxides in biological samples is often attempted with methods that have low sensitivity, low validity, and/or low reliability. The highly sensitive and specific enzymatic assay based upon cyclooxygenase activation has many complex kinetic features that have caused it to be cumbersome and unreliable. Analysis of the cyclooxygenase kinetics showed that a fixed percentage (20%) of full reaction accurately substituted for the measurements of the time required to reach optimal velocity. Consequently, a voltage-responsive timer can report endpoints that are dependent upon picomole amounts of lipid hydroperoxide. Additional features of the timer are described which make the hydroperoxide assay simpler, faster, more reliable, and easier to perform than the previous method while still retaining its sensitivity and specificity. PMID- 1904204 TI - Preparation of solutions with free calcium concentration in the nanomolar range using 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid. AB - There are many uses for solutions with a known free calcium concentration ([Ca2+]free) in the nanomolar range. Most frequently ethylene glycol bis(beta aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) has been used as a buffer for the control of [Ca2+]free; however, under a variety of conditions the use of 1,2 bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) for this purpose would be advantageous. The theory and calculations necessary to make solutions with known [Ca2+]free appropriate for given conditions of pH, ionic strength, and temperature for use with EGTA or BAPTA are reviewed. Practical considerations and methods for making such solutions are detailed. The advantages and disadvantages associated with the use of each of the two chelators are discussed. As one example of the application of solutions with free calcium in the nanomolar range, the dissociation constant of the fluorescent indicator fura-2 for calcium has been determined in a physiologic buffer at 22 and 37 degrees C. For practical reasons, the use of BAPTA is advantageous when solutions with different known [Ca2+]free must be used on a daily basis. PMID- 1904205 TI - Differences in cerebral blood flow between alpha-stat and pH-stat management are eliminated during periods of decreased systemic flow and pressure. A study during cardiopulmonary bypass in rabbits. AB - Prior reports suggest cerebral blood flow (CBF) responses to changing bypass (systemic) flow rates may differ between alpha-stat and pH-stat management. To compare the effect of blood gas management upon CBF responses to changing systemic flow and pressure, 15 New Zealand White rabbits, anesthetized with fentanyl and diazepam, underwent nonpulsatile cardiopulmonary bypass at 25 degrees C. One group of animals (n = 8) was randomized to alpha-stat blood gas management that maintained arterial carbon dioxide tension (PaCO2) approximately 40 mmHg when measured at 37 degrees C. A second group (n = 7) was managed with pH stat technique, maintaining PaCO2 approximately 40 mmHg when corrected to the animal's actual temperature. Bypass was initiated at a flow rate of 100 ml.kg 1.min-1 and, after approximately 20 min, control hemodynamic and CBF measurements (radioactive microspheres) were made. Thereafter, bypass flow rate was changed in random order at 15-min intervals to 50, 70, and 100 ml.kg-1.min-1. CBF and hemodynamic measurements were repeated at the end of each period of altered bypass flow. Groups differed significantly with respect to both pHa and PaCO2. There were no significant differences between groups with respect to bypass flow rate, mean arterial pressure (MAP), central venous pressure, temperature, hematocrit, arterial oxygen tension (PaCO2), or bypass duration at any measurement point. MAP decreased significantly, from approximately 80 to approximately 65 mmHg with decreasing bypass flow (P = 0.0001). Over the entire range of bypass flows, CBF decreased with decreasing bypass flow (P = 0.001), and the degree of change was equivalent among regions and between groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1904206 TI - A single-blind study of combined pulse oximetry and capnography in children. AB - This single-blind study examined four levels of monitoring in 402 pediatric cases. Patients were randomly assigned to one of four groups: 1) oximeter and capnograph; 2) only oximeter; 3) only capnograph; or 4) neither oximeter nor capnograph data available to the anesthesia team. An anesthesiologist, not involved in patient care, observed all cases and continuously recorded hemoglobin oxygen saturation (Spo2), ECG, expired CO2, and the oximeter plethysmographic output. Mean age, weight, ASA physical status, airway management (mask or endotracheal tube), and anesthetic technique were similar in each group. Two hundred sixty problems were documented in 153 patients. Fifty-nine events in 43 patients resulted in "major" desaturation (Spo2 less than or equal to 85% for greater than or equal to 30 s). Fifteen "major" capnograph events (esophageal intubation, disconnection, accidental extubation, or obstructed endotracheal tube) were observed in 11 patients; 8 of these also developed varying degrees of desaturation. One-hundred thirty "minor" desaturation events (Spo2 less than or equal to 95% for greater than 60 s) and 79 "minor" desaturation events (hypercarbaria or hypocarbia) were observed. A number of problems fulfilled criteria in multiple categories. Infants less than or equal to 6 months of age had the highest incidence of major desaturation events (18 of 65 [27%]) compared to toddlers 7-24 months of age or children greater than 24 months of age (P less than 0.001). Blinding the oximeter data increased the number of patients (12 vs. 31) experiencing major desaturation events (P = 0.003); blinding the capnograph data altered neither the frequency of desaturation events nor the incidence of major capnograph events.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1904207 TI - Plasma cholesterol and lipoprotein levels during fetal development and infancy. AB - Intrauterine changes in plasma cholesterol and lipoprotein concentrations have been linked to the development of the adrenal gland (utilization of cholesterol) and liver (production of cholesterol by new synthesis). At term birth, racial and gender differences have been observed with white compared to black, and female compared to male, infants having higher cholesterol concentrations. Within hours of the beginning of oral feeding, total and LDL cholesterol rise significantly. Little further increase occurs after 7 days, and the concentration seen after this time is highly dependent upon the cholesterol and polyunsaturated fat content of the diet. By 12 months of age, investigators cease to find any effect of the milk source fed earlier in infancy on cholesterol and lipoproteins. This is not evidence that diet no longer influences cholesterol and lipoprotein concentrations, but only that individual lipid intakes are varied and difficult to quantitate. Cross-cultural comparisons of infants at this age in fact provide strong suggestive evidence that a large environmental component determines the circulating cholesterol and lipoprotein concentrations seen at one year and beyond. PMID- 1904208 TI - Immunomodulatory effects in vivo of recombinant porcine interferon gamma on leukocyte functions of immunosuppressed pigs. AB - Immunological parameters of porcine peripheral blood mononuclear cells after in vivo injections of recombinant porcine interferon gamma (rPoIFN gamma) were studied in pigs immunosuppressed by dexamethasone (6 mg/kg body weight in a single injection). A 2-d period of rPoIFN gamma injected alone and intramuscularly at a dose of 1 microgram/kg body weight increased interleukin 1 (IL1) production (P less than 0.05). Recombinant porcine IFN gamma also reversed the immunosuppressive effects of dexamethasone on: i), lymphocyte responsiveness to mitogens: PHA (P less than 0.03), ConA (P less than 0.053); ii), IL1 production; and iii), IL2 production (P less than 0.05). However, rPoIFN gamma had no effect on neutrophilia induced by dexamethasone. These data show that rPoIFN gamma modulates leukocyte functions of pigs in vivo. PMID- 1904209 TI - Receptor-G protein signaling in yeast. PMID- 1904210 TI - Disabling ossification of the patellar tendon. PMID- 1904211 TI - Should the elderly be screened for hypercholesterolemia? PMID- 1904212 TI - Costs and health consequences of cholesterol screening for asymptomatic older Americans. AB - To predict the consequences of cholesterol screening among elderly Americans who do not have symptoms of heart disease, we explore the cost implications of a cholesterol screening program, evaluate evidence linking hypercholesterolemia to coronary heart disease and mortality in the elderly, and describe the likely effects of therapy of hypercholesterolemia. According to our calculations, if all Americans 65 years of age and older adhered to a cholesterol screening program similar to the one proposed by the National Cholesterol Education Program, minimum annual expenditures for screening and treatment would be between $1.6 billion and $16.8 billion, depending on the effectiveness of diet and the cost of the medications used to treat hypercholesterolemia. There is no direct evidence that this program would lessen overall morbidity or extend the lives of elderly Americans. PMID- 1904213 TI - Cost-benefit issues in the practice of internal medicine. AB - The rapidly escalating costs of medical treatment would suggest that everything be done to limit expenses when it can be done without jeopardizing patient care. Unfortunately, cost consciousness is a relatively new concept for most physicians and even today is not emphasized in most medical education programs. Over the past five years numerous articles have been published indicating ways in which specific cost-effective measures can be taken that can positively influence the cost of routine medical care. This article details a number of well-documented steps practicing physicians might consider to decrease the cost of medical treatment without compromising patient care. PMID- 1904214 TI - [The effect of the vasoconstrictor glycylpressin on the bioavailability of mitomycin C]. AB - During an intra-arterial chemotherapy of patients with liver metastases the plasma concentration-time curves of Mitomycin C (1) after occlusion of the common hepatic artery by the vasoconstricting agent Glycylpressin (2) were investigated. Vasoconstriction by 2 leads to significantly (p less than 0.01) lower blood levels of 1 in contrast to bolus injection of 1 without 2 under identical dosage regimens. This reduction of systemic availability of about 50% leads to a corresponding higher availability for the tumor region. PMID- 1904215 TI - Cloning and sequencing of the ovine gamma-interferon gene. AB - Cytokines are major modulators of the immune system of all animals. The cloning and expression of recombinant cytokine genes have permitted the analysis of their immune function and role in the control of the immune response to disease and vaccination. While human, murine, and bovine genes have been cloned and sequenced, the cloning of ovine cytokine genes has not yet been reported. As sheep are of dominant economic importance to the Australian farming industry, it is of significance to clone and express these genes to facilitate the development of new and better vaccines and pharmaceuticals. We have initially selected ovine gamma-interferon (gamma-IFN) as a target cytokine gene. By the use of the polymerase chain reaction (PCR), using primers based on the bovine gamma interferon sequence, we have amplified the ovine gamma-interferon gene from crude messenger RNA extracted from lymphocytes. After cloning and DNA sequencing the gene, we found that ovine gamma-IFN is 93% identical to bovine gamma-IFN in amino acid sequence. This result indicates that the PCR method will be a rapid and efficient means for cloning other ovine cytokine genes. PMID- 1904216 TI - Multiple forms of NADPH-cytochrome P450 reductase in higher plants. AB - We report on the presence of multiple forms of NADPH-cyt P450 reductase in microsomes from higher plants. This contrasts with the animal cyt P450 monooxygenases, where the numerous cyt P450 isoforms are reduced by a single form of reductase. Three NADPH-cyt c reductases have been resolved from Jerusalem artichoke tuber microsomes by chromatography on Reactive Red Agarose and Concanavalin A-Sepharose. Their molecular weights, determined by sodium dodecylsulfate-gel electrophoresis, are 80,000, 82,000 and 84,000. The three proteins share common epitopes and are dependent upon FMN for catalytic activity. They are highly selective for NADPH as electron donor, and allowed effective reconstitution of trans-cinnamic acid and 3,9-dihydroxypterocarpan 6a-hydroxylase activities with purified cyt P450 fractions from Helianthus tuberosus and Glycine max, respectively. As such, they appear as true isoenzyme forms of NADPH-cyt P 450 reductase. PMID- 1904218 TI - Expression of functional beta-galactosidase containing the coxsackievirus 3C protease as an internal fusion. AB - Alpha complementation of beta-galactosidase (beta gal) is intracistronic and requires interaction between the alpha donor region (residues 3-41) and alpha acceptor fragment (produced by M15). We have constructed two plasmids which direct the synthesis of hybrid beta gal: coxsackievirus proteins in Escherichia coli. One plasmid, pBD1045, encodes an enzymatically active 3C protease of coxsackievirus B3 fused between the amino-terminal 79 amino acids of beta gal (containing the alpha donor region) and amino acids 80 to 1023 (alpha acceptor region). A second plasmid, pBD1043 encodes an inactive 3C protease and results in a fusion of 260 coxsackievirus amino acids between residues 79 and 80 of the beta gal monomer. Both hybrid proteins expressed by these constructs have beta galactosidase activity regardless of whether the viral protease (183 amino acids) is autocatalytically cleaved out of the chimeric protein (pBD1045) or remains as part of a fusion protein (pBD1043). The implications of these results for structural flexibility of the complemented beta-galactosidase enzyme are discussed. PMID- 1904217 TI - Modulation of phospholipase A2 activity in zymogen granule membranes by GTP[S]; evidence for GTP-binding protein regulation. AB - In membranes associated with purified pancreatic zymogen granules, GTP[S] elicited a concentration-dependent activation of phospholipase A2 (PLA2), which was converted to inhibition in the presence of added Ca2+. The GTP-binding protein inhibitor GDP[S] blocked both the stimulatory and inhibitory actions of GTP[S]. We conclude that in zymogen granule membranes GTP-binding proteins exert a dual regulation of PLA2 activity. PMID- 1904219 TI - Tb(III) as a fluorescent probe for the structure of bovine serum albumin. AB - Tb(III) was used as a fluorescent probe in the study of the calcium-binding sites on Bovine Serum Albumin (BSA). The fluorescence of Tb(III) is enhanced markedly when bound to BSA and nonradiative energy transfer between two fluorescent tryptophan(Trp) residues and Tb(III) bound to calcium-binding sites on BSA occurred. Experimental results show that the major groups in BSA bound to metal ion are the carboxyl side groups of glutamic acid (Glu) and aspartic acid (Asp). The average distance between the bound Tb(III) and the two tryptophan residues in BSA calculated by a Foster dipole-dipole nonradiative energy transfer mechanism is 1.48 nm. PMID- 1904220 TI - A simple convenient biological dosimeter for monitoring solar UV-B radiation. AB - The use of dry Bacillus subtilis spores as a biological dosimeter for the monitoring of solar UV-B (290-330 nm) radiation was described. Our field tests had supported the utility of this dosimeter as a reproducible and reliable sunlight dosimeter. PMID- 1904221 TI - Cyclophellitol: a naturally occurring mechanism-based inactivator of beta glucosidases. AB - The natural product cyclophellitol, isolated from the culture filtrate of a mushroom, Phellinus sp. is found to be a highly specific and effective irreversible inactivator of beta-glucosidases. It inactivates the beta glucosidases from both almond emulsin and Agrobacter sp. according to pseudo first order kinetics with inactivation constants of Ki = 0.34 mM, ki = 2.38 min 1, and Ki = 0.055 mM, ki = 1.26 min-1 respectively. No reactivation of the inactivated enzyme is seen upon dialysis, thus providing evidence for the irreversibility of the inactivation. The high specificity of this inactivator is evidenced by the fact that even at very high (12 mM) concentrations of cyclophellitol, no inactivation of yeast alpha-glucosidase was observed, and only extremely slow (t1/2 greater than 5 hours) inactivation of E. coli beta galactosidase could be detected. PMID- 1904222 TI - The effects of histamine H2 receptor antagonists on melanogenesis and cellular proliferation in melanoma cells in culture. AB - B16-C3 murine melanoma, A375P human melanotic melanoma, and C32 human amelanotic melanoma cells were incubated in the presence of (0-4 mM) H2-antagonists, ranitidine and cimetidine. Cell proliferation, tyrosinase activity and melanin content were monitored. H2-antagonists stimulated tyrosinase activity and melanin accumulation in B16-C3 cells in a dose- and time-dependent manner. Stimulation of enzyme activity and pigment production was accompanied by inhibition of cellular proliferation in B16-C3 cells. The inhibitory concentration of cimetidine was approximately 2-fold higher than that of ranitidine. H2-antagonists failed to stimulate melanogenesis in A375P or C32 cells, but inhibited cellular proliferation in both cell lines. These results are the first demonstration of H2 antagonist induced phenotypic changes in malignant melanoma cells in vitro, and represent a novel mechanism for the previously described in vivo antitumor effects of these agents. PMID- 1904223 TI - Antibody against neurofibromatosis type 1 gene product reacts with a triton insoluble GTPase activating protein toward ras p21. AB - Cellular fractionation of GTPase activating protein (GAP) activity using bovine cerebral cortex revealed that about half of GAP activity was found in membrane fraction. GAP activity of membrane was not solubilized with 0.5% (v/v) triton X 100 and was immunoprecipitated with antibody against carboxy-terminus of neurofibromatosis type 1 (NF1) gene product. In contrast, soluble GAP activity was precipitated with antibody against GAP but not with anti-NF1. These results suggest that NF1 gene product is a GTPase activating protein toward ras p21 with completely different intracellular distribution from that of GAP. PMID- 1904224 TI - Non-steroidal anti-inflammatory drugs: effects on a GTP binding protein within the neutrophil plasma membrane. AB - Sodium salicylate and other non-steroidal anti-inflammatory drugs (NSAIDs) inhibit neutrophil functions via unknown mechanisms. To examine their site of action in the neutrophil we have studied discrete events within the plasma membrane which depend upon the normal function of a GTP binding protein (G protein). We demonstrated that sodium salicylate and piroxicam inhibit neutrophil activation in response to stimuli which require signal transduction via a G protein (e.g. formyl-methionine-leucine-phenylalanine) but have no effect on stimuli which do not (e.g. phorbol myristate acetate, ionomycin). NSAIDs blocked the ADP-ribosylation of the pertussis toxin substrate in human neutrophils. This effect was associated with the capacity of NSAIDs to block pertussis toxin dependent inhibition of neutrophil functions. Finally, NSAIDs inhibited the binding of GTP gamma S, a stable analog of GTP, to purified neutrophil membrane preparations. The data indicate that salicylate and other NSAIDs interact with a G protein in the neutrophil plasmalemma and thereby uncouple post-receptor signaling events. PMID- 1904225 TI - Drug metabolizing enzyme activities in rat liver epithelial cell lines, hepatocytes and bile duct cells. AB - P450-dependent mono-oxygenase and conjugating enzyme activities were studied in rat liver epithelial cells (RLEs) and compared to those in hepatocytes and bile duct cells. Various RLE cell lines were investigated since (a) they are suspected to be derived from cells in the lineage from putative pluripotent stem cells to either hepatocytes or bile duct cells, and (b) they may represent targets of chemical carcinogens. Despite considerable variation between lines, common features were recognized. P450-dependent monooxygenase activities (7 ethoxyresorufin O-deethylase and 7-ethoxycoumarin O-deethylase) were undetectable in all RLEs and bile duct cells, and were uninducible by benz(a)anthracene. In contrast, glucuronosyltransferase (GT), sulfotransferase and GSH transferase activities were clearly detectable. Conjugating enzyme activities increased until confluency of the cell cultures was reached. Under the latter conditions, GT activities towards 4-methylumbelliferone or benzo(a)pyrene-3,6-quinol (substrates of a 3-methylcholanthrene-inducible phenol GT) were similar to those found in hepatocytes or bile duct cells. Using a selective cDNA probe, phenol GT mRNA was clearly detectable in RLE1. In contrast, GT activity towards 4-hydroxybiphenyl was much lower than in hepatocytes or bile duct cells (0.04- and 0.03-fold). Sulfotransferase and GSH transferase activities were also roughly comparable to those found in hepatocytes and in bile duct cells. The results suggest that RLEs and bile duct cells exhibit both high conjugating enzyme activities and a lack of P450-dependent mono-oxygenase activities, a pattern resembling the 'toxin resistance phenotype' found in putative preneoplastic hepatocyte foci and nodules. PMID- 1904226 TI - Effect of ethyl apovincaminate on the utilization of 14C-glucoses by rat brain in vitro. AB - The effect of the presence of 500 micrograms ethyl epovincaminate (Cavinton) on the aerobic metabolism of 14C-labelled glucoses was studied in vitro. The drug tested increased the metabolism of [1-14C]-D-glucose first of all, which indicated a significant activation of pentose-phosphate shunt. PMID- 1904227 TI - Inhibitory effect of dietary administration of eicosapentaenoic acid on the contractions of guinea-pig tracheal smooth muscle induced by leukotriene C4 and D4. AB - The changes in fatty acid composition in phospholipids of guinea-pig lung parenchymal strips and trachea induced by dietary administration of eicosapentaenoic acid (EPA) were investigated as well as the resultant changes in leukotriene (LT) C4- and D4-induced contractions of guinea-pig tracheal smooth muscle. EPA levels in both parenchymal strips and trachea were significantly increased depending on the administered dose of EPA, but on the other hand, arachidonic acid levels in those preparations were not changed. Both the contractions of guinea-pig tracheal smooth muscle induced by LTC4 and D4 were significantly reduced in the EPA-treated group compared with the control group at all 3 concentrations, 10(-9), 3 x 10(-9) and 10(-8) mol/l, in the presence of 5 x 10(-5) mol/l indometacin, a cyclooxygenase inhibitor. But this significant reduction of the contraction was not recognized between these 2 groups in the presence of 10(-5) mol/l 2-(12-hydroxydodeca-5, 10-diynyl)-3,5,6-trimethyl-1,4 benzoquinone (AA861), a 5-lipoxygenase inhibitor, or in the combined presence of 5 x 10(-5) mol/l indometacin and 10(-5) mol/l of AA861. These results suggest that: 1. a 5-lipoxygenase pathway is partly involved in the contractions of guinea-pig tracheal smooth muscle induced by LTC4 and D4 and; 2. EPA suppresses LTC4- and D4-induced contractions of guinea-pig tracheal smooth muscle through a 5-lipoxygenase pathway. PMID- 1904228 TI - Determination of the synergy of antibiotic combinations by an overlay inoculum susceptibility disc method. AB - A method involving an overlay inoculum agar and antibiotic susceptibility discs in the determination of synergy of gentamicin and disc antibiotics against clinical isolates of Pseudomonas aeruginosa has been described. Gentamicin combinations with carbenicillin showed synergism against all test isolates. Combinations containing fosfomycin had indifferent effects. Netilmicin, ceftriaxone and ampicillin, respectively, produced interisolate variations in the synergy of their combinations with gentamicin. In all cases synergy was determined on the basis of correlations between inhibition zone diameter (IZD) increments and fractional inhibitory concentration (FIC) indices. An IZD increment of 19% or more predominantly corresponded with synergy. Cases showing less than 19% increase in IZD produced additive effects, while cases showing no variations in IZD had indifferent effects. PMID- 1904229 TI - [Inhibition of arachidonic acid cascade by extract of rye pollen]. AB - A standardized extract mainly from rye pollen (Cernilton N) was tested in vitro on the inhibition of prostaglandin and leukotrien synthesis. The determination of the prostaglandin and leukotrien synthesis from labelled arachidonic acid was done in microsomes of ram seminal vesicles resp. in rat basophilic leukemia cells (RBL-1 cells). The water soluble resp. the fat soluble extract fraction from the whole pollen extract were tested separately. The radio-TLC separation of the reaction metabolites showed a dose dependent inhibition of the cyclo-oxygenase and the 5-lipoxygenase activity by the fat soluble pollen extract fraction. The IC50-values are 0.005 mg/ml resp. 0.08 mg/ml and similar to those of the also tested diclofenac. The water soluble fractions showed no effect in this test system. According to these in vitro results and the clinical experience so far with the pollen extract its therapeutic efficacy on benign prostate diseases is best explainable by the anticongestive resp. anti-inflammatory effect of the fat soluble fraction. Due to the different actions of prostaglandins and leucotrienes also relaxant and antiproliferative effects were conceivable. PMID- 1904230 TI - Mast cell tumours in CD-1 mice. AB - A survey of the occurrence of mast cell tumours in CD-1 mice (Caesarian derived) recorded nine tumours in 24352 mice used for carcinogenicity studies over a period of six years (1984-1989). All except one appeared as multi centric tumours. Three of the mice had deposits only in the bone marrow, one of those cases was associated with intestinal adenocarcinoma and harderian gland adenoma. Case four had deposits in lung, thymus, lymph nodes, liver, spleen and kidney and occurred in association with pulmonary adenocarcinoma and pleomorphic lymphoma. Case five showed the tumour deposits in mesenteric lymph nodes and liver. Case six showed deposits of the tumour in lung, liver, kidney and bone marrow and in this case there was also a cutaneous fibrosarcoma. Case seven was diagnosed as mast cell leukaemia. Case eight was a subcutaneous tumour, case nine showed subcutaneous deposits and deposits in lungs, lymph nodes, liver, spleen and bone marrow. PMID- 1904231 TI - Endocytosis of the recombinant tissue plasminogen activator alteplase by hepatic endothelial cells. AB - The glycoprotein tissue-type plasminogen activator (t-PA, alteplase, CAS 105857 23-6) is a serine protease consisting of 527 amino acids and can activate plasminogen to plasmin, which subsequently dissolves the fibrin network of a thrombus. This activation occurs selectively on the thrombus, making recombinant t-PA a very effective agent in the treatment of thromboembolic disorders. t-PA has a short in vivo half-life and is rapidly removed from the circulation by the liver. The catabolism of t-PA involves receptor-mediated endocytosis and intracellular degradation in several cell types of the liver namely hepatic endothelial, parenchymal and Kupffer cells. Liver endothelial cells have been reported to possess a specific uptake system for t-PA based on the recognition of the high mannose carbohydrate structures on Asn117. To further elucidate the involvement of the mannose receptor on sinusoidal endothelial cells in the hepatic catabolism of t-PA and to identify the mechanisms involved, biochemical as well as electron microscopic studies were performed. The biochemical studies revealed that the removal of the mannose side chain in t-PA significantly reduced its clearance and degradation in isolated perfused livers. The binding of t-PA to preparations of primary hepatocytes and liver cell membranes could not be competed for by various sugars and glycoproteins, and was not dependent on the presence of carbohydrates on the molecule. This ruled out a major relevance of the sugar moieties of t-PA in its recognition by liver cells that were not of endothelial origin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1904232 TI - Nutritional considerations in AIDS. PMID- 1904233 TI - [Capnometry and capnography as safety factors in anesthesia]. AB - Continuous measurement and monitoring of the expiratory carbon dioxide concentration can be performed with modern measurement devices routinely without any problem today. After a short introduction to measurement techniques the comprehensive monitoring possibilities of this method are described by multiple examples. No only actual disturbances of the ventilation, the circulation and the metabolism, but also malfunction or inadequate control of the anaesthesia machine can be recognized without substantial time delay. But an actual alteration of the CO2 value necessitates careful analysis of the underlying problem which is greatly facilitated by a graphic display of the CO2 signal, the capnogram. The knowledge of possibly occurring artificial alterations of the CO2 measurement, which are demonstrated too, prevents dangerous misinterpretations. By continuous measurement of the expiratory CO2 concentration, not only can the ventilation parameters be set optimally, but multiple life threatening complications can be detected very early and corrected immediately. Thus, this monitoring technique essentially contributes to the patients safety during anaesthesia. PMID- 1904234 TI - Inverse effects of activin and inhibin on the synthesis and secretion of FSH and LH by ovine pituitary cells in vitro. AB - Little information is available on the effects of activin and inhibin on the synthesis and secretion of pituitary gonadotrophins in species other than the rat. In this in-vitro study, ovine pituitary cell cultures derived from immature sheep were used to investigate the effects of recombinant human activin-A and native Mr 32,000 bovine inhibin on basal and gonadotrophin-releasing hormone (GnRH)-induced release of FSH and LH. Residual cellular contents of FSH and LH were also determined, allowing total content/well to be calculated. Activin-A promoted a dose-dependent increase in basal (+72%; P less than 0.001) and GnRH induced (+25%; P less than 0.001) release of FSH as well as in the residual cell content (+114%; P less than 0.001) and total FSH content/well (+67%; P less than 0.001). Conversely, inhibin significantly (P less than 0.001) suppressed each aspect of FSH production examined, confirming that in sheep, as in rats, activin and inhibin exert opposing effects on pituitary FSH production. In contrast to the rat, however, in which activin is reported to have no effect on LH secretion, exposure of sheep pituitary cells to activin-A promoted a dose-dependent suppression (-42%; P less than 0.001) of GnRH-induced LH release. This was associated with a corresponding increase (P less than 0.001) in residual cellular content of LH. Consistent with a previous report from this laboratory, inhibin had the opposite effect and significantly enhanced (+47%; P less than 0.001) GnRH induced LH release. This was associated with a corresponding fall (P less than 0.01) in residual cellular content of LH.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1904236 TI - Introducing a computerized record and verify system: its impact on the reduction of treatment errors. AB - A survey of treatment errors has been conducted over a period of several months before and after the introduction of a CMS computerized record and verify system for radiation treatments administered on a Varian CL-1800 accelerator. It was found that treatment errors could be reduced considerably. However, some errors were also caused by wrong data entry into the system. In two instances, errors were detected only through the record and verify system; they had escaped all previous chart checks and would never have been found otherwise. The impact of the computerized record and verify system is analyzed with regard to improved treatment delivery, reception by technologists, and treatment documentation. PMID- 1904235 TI - Growth hormone induces expression of c-jun and jun B oncogenes and employs a protein kinase C signal transduction pathway for the induction of c-fos oncogene expression. AB - Although the structure of several members of the GH receptor family has been defined, signal transduction following GH binding to its receptor has not been elucidated. Mouse osteoblasts were used to study the effect of GH on immediate early gene expression and, subsequently, the cellular signal(s) mediating this expression were analysed. GH rapidly and transiently induced the expression of c jun and jun B in concert with the already reported expression of c-fos. The GH induced expression of c-fos was completely blocked by the protein kinase inhibitors staurosporine and H7, indicating that the action of GH is mediated by one or several protein kinases. We next analysed the identity of the putative protein kinases in more detail by using a more specific protein kinase inhibitor, namely the ether-lipid 1-O-alkyl-2-O-methylglycerol, understood to be an inhibitor of protein kinase C (PKC). Data obtained from these studies revealed that GH-induced expression of c-fos is mediated by PKC. In addition, we observed a profound increase in formation of the PKC activator diacyglycerol upon addition of GH, a natural activator of PKC. In conclusion, upon binding of GH to mouse osteoblasts, the receptor-mediated cellular signal involves diacyglycerol formation and activation of PKC, leading to the induction of oncogene expression. Finally, the expression of c-fos, c-jun and jun B results in an increased binding of protein complexes to AP-1 binding sites. PMID- 1904237 TI - Depth dose and profile analysis using Library Least-Squares method. AB - The Library Least-Squares method has been applied to detect changes in the depth dose and in the profiles of 6 and 20 MeV electron beams, and in 6 MeV photon beams from medical linear accelerators. The changes in the beam energy of 0.78% and 0.32% at low and high electron energies, respectively, induced by the insertion of 0.1 mm A1 absorber were clearly visible in the residual distributions. The changes in the photon beam were introduced by rotation of the gantry or the collimator. The applicability of the method to quantitatively monitor any changes in the treatment beam characteristics is presented. PMID- 1904238 TI - Measurement of skin dose in primary irradiation of maxillary sinus carcinoma. AB - Subcutaneous involvement frequently occurs in maxillary sinus carcinoma. Radical resection does not include removal of the skin at risk. In standard postoperative wedge-pair treatment plans, the surface dose is dependent upon beam weighting, beam energy, and patient contour. Thermoluminescent dosimetry (TLD) measurements were performed to evaluate the surface dose of patients undergoing postoperative irradiation of maxillary sinus carcinoma following primary resection. When 60 Gy was delivered to isocenter with a 45 degrees wedge pair and 6 MV photons with 1 cm bolus, the subcutaneous tissues at risk received approximately 30 Gy. Based upon presented TLD measurements, supplemental electron beam therapy to the subcutaneous tissues if primarily involved should be considered. PMID- 1904239 TI - [The inspection. Innovation project residential psychiatry in a new phase]. PMID- 1904241 TI - [Institution Haarendael in Haaren. The advantage of a retailer's diploma]. PMID- 1904240 TI - ['I can still be myself when I'm in a dark room'. Skin disorders in AIDS]. PMID- 1904242 TI - [The Advisory Committee of the EEC and Europe '92]. PMID- 1904243 TI - [The district nurse and the central caregiver (2). Alternate forms of assistance]. PMID- 1904244 TI - [Home care--Quality control--Information services]. PMID- 1904245 TI - Effect of phenolic compounds and oleuropein on the germination of Bacillus cereus T spores. AB - The phenolic compounds extracted from olives with ethyl acetate inhibited germination and outgrowth of Bacillus cereus T spores. Purified oleuropein, a well-characterized component of olive extract, inhibited these processes also. The addition of oleuropein and olive extracts 3 or 5 min after germination began, immediately decreased the rate of change of phase bright to phase dark spores and delayed significantly outgrowth. PMID- 1904246 TI - Laminarinase from Penicillium funiculosum and its role in release of beta glucosidase. AB - An extracellular laminarinase (1----3)-beta-glucan glucohydrolase (EC 3.2.1.6) was purified from culture filtrates of Penicillium funiculosum. It was homogeneous on polyacrylamide gel electrophoresis in the presence and absence of sodium dodecyl sulfate. It had a Mr of 14,000 and isoelectric point of pH 4.2. The apparent Km value for lamimarinase was 8.3 mg/ml and Vmax was 8 mumol/min/mg. The distribution of beta-glucosidase activity in two different species of Penicillium showed that P. funiculosum had a higher ratio of extracellular to cell wall bound activity than Penicillium janthinellum. Treatment of mycelia of both species with NaCl, EDTA, Triton X-100, or proteolytic enzymes did not release the cell wall bound beta-glucosidase. Incubation of the mycelia with the laminarinase released 2-4 times more beta-glucosidase than the estimated cell bound activity in P. janthinellum and P. funiculosum. PMID- 1904247 TI - Thiotepa. PMID- 1904249 TI - Isozymes of ribonuclease and the changes in their relative levels during development in the cellular slime mould Dictyostelium discoideum. AB - The isozymes of ribonuclease were analyzed in cell-free, crude extracts of Dictyostelium discoideum by activity staining of polyacrylamide gels after electrophoresis. The relative levels of three isozymes were then examined during the growth and during the first stages of multicellular development. We observed the replacement of two of these three isozymes by two other isozymes at the pseudoplasmodial stage. These isozymes were different from ribonuclease T1 in terms of their mobility in polyacrylamide gels during electrophoresis. The mobilities of two of the isozymes, DdI and DdII, were 59 and 42% of that of ribonuclease T1. The changes in the relative levels of the isozymes during development are discussed. PMID- 1904248 TI - Newly synthesized glycoconjugates from two cell lines derived from rat osteogenic sarcoma: effects of Matrigenin activity from bone. AB - An activity isolated from bovine bone was previously shown to stimulate proteoglycan synthesis by several connective tissue cell lines from normal tissues (Matrigenin activity). The effect of this activity on glycoconjugate synthesis by two osteoblastic cell lines, ROS 17/2 and UMR-106, derived from rat osteogenic sarcoma, was examined after labelling of the cells with [3H]glucosamine and [35S]sulfate. The glycoconjugates from the cell layers and the media were separated by DEAE-Sephacel chromatography and the anionic glycoconjugates of the media were further analyzed by chromatography on Sepharose CL-2B and enzymatic digestion of the papain-released glycosaminoglycans. The ROS 17/2 cells secreted at least two distinct species of proteoglycan (one heparan sulfate rich and the other chondroitin sulfate rich), whereas the UMR-106 secreted primarily an anionic glycoprotein. The addition of Matrigenin activity to the ROS 17/2 cells resulted in stimulation of incorporation of radioactivity into the proteoglycan and hyaluronic acid, but in UMR-106 cultures it resulted in decreased incorporation into the anionic glycoprotein. The decrease in incorporation into the anionic glycoprotein from the medium was shown, by alkaline beta-elimination, to have occurred mainly in the oligosaccharide fraction, relative to control cultures. PMID- 1904250 TI - The effects of blockade of interleukin 2 receptors and interleukin 4 receptors on cytokine production. AB - The understanding of the regulation of cytokine production and T-cell proliferation by other cytokines is far from complete. We have examined the supernatant concentration of different cytokines in cultured peripheral blood lymphocytes (PBL) incubated with monoclonal antibodies against the interleukin-2 receptor (IL-2R) or interleukin-4 receptor (IL-4R) complex in order to analyse the importance of these receptors in the production of other cytokines. The PBL cultures were stimulated with phytohaemagglutinin and phorbol myristate acetate. The addition of anti-Tac to PBL cultures resulted in increased free IL-2 due to blockade of IL-2R. MR6 (a monoclonal antibody against IL-4R) did not affect the supernatant concentration of IL-2 in cultured PBL. Blockade of IL-2R or IL-4R both resulted in increased IL-4 in supernatant. The increase in supernatant concentration of IL-4 in PBL cultured with MR6 was due to a direct interaction with the IL-4R complex but the increase in IL-4 with anti-Tac was due to the accumulation of free IL-4 as an effective blockade of IL-2R prevented the full expression of IL-4R. Neither anti-Tac nor MR6 affected the IL-6 production by activated PBL, suggesting the existence of an IL-2- and IL-4-independent pathway. Blockade of IL-2R or IL-4R both resulted in a reduction of interferon-gamma (IFN gamma) production, indicating that both endogenously generated IL-2 and IL-4 are important mediators of IFN-gamma induction in PBL cultures stimulated with T-cell mitogens. PMID- 1904251 TI - ELISA for detection of Mycoplasma pneumoniae antigens using monoclonal antibodies. AB - Seven monoclonal antibodies directed against major antigens of Mycoplasma pneumoniae were selected for the development of an antigen detection assay. Three of these were directed to the 170,000-dalton adhesin of M. pneumoniae. The test was an antigen-capture enzyme immunoassay using the different monoclonal antibodies for capture of antigen and a polyclonal rabbit antiserum as detection reagent. With three of the monoclonal antibodies a detection limit of approximately 2 ng M. pneumoniae protein was obtained, as determined by titration of M. pneumoniae organisms in buffer. The detection limit of the assays was only slightly less when the other four monoclonal antibodies were used. In artificially infected nasopharyngeal aspirates the detection limit was approximately 10 times lower. The fact that no significant differences in the detection limit of the assays were recorded using monoclonal antibodies directed against different antigens indicates that these antigens were available for reaction with antibodies irrespective of their location in intact M. pneumoniae cells. In the assay there were no significant cross-reactions with a number of bacterial species potentially colonizing the respiratory tract, except for a protein A-positive strain of Staphylococcus aureus. Our test is equally sensitive to another recently described ELISA using polyclonal antibodies. In comparison with other recommended methods such as immunoblot and culture-amplified antigen detection assays, the ELISA is more rapid and less laborious. PMID- 1904252 TI - [Radiological studies of feeding disorders in severely retarded children]. AB - Feeding difficulty is a major problem in severely retarded children. Fourteen patients aged from 5 to 36 years with physical and intellectual impairments who had feeding difficulties were investigated by videofluoroscopy. Video fluoroscopic findings showed that the liquid was easier to be aspirated than the paste, and that in the sitting position aspirations were more frequent than in the supine. The predisposing factors of feeding difficulties were thought to be poor bolus formation by the tongue, delayed swallowing reflex, incomplete closure of the larynx and poor pharyngeal pressure. Of ten cases that showed markedly gulped air, three of them had gastro-esophageal reflux, which was very likely caused by the increased intragastric pressure. Seven patients fed by nasogastric tube feeding were examined their swallowing ability by dropping contrast medium into the oral cavity. Three patients aspirated contrast media into bronchi. This suggests that they also generally aspirated saliva which resulted in recurrent respiratory infection. It is therefore important to maintain the swallowing function in patients fed by nasogastric tube. Low osmolality water soluble contrast medium was used in this study. There were no complications. This medium is thought to be safer than the standard media of barium solutions or other high osmolality contrast media, especially for the patients who suffer from aspiration. PMID- 1904253 TI - [P300 latencies in epileptic children: the differences among various epileptic syndromes]. AB - Auditory event-related potentials (ERPs) were recorded from 129 epileptic children of 5 to 20 years of age. To clarify the developmental changes in each of the epileptic syndromes, P300 latencies of ERPs were examined. ERPs were elicited with the auditory oddball paradigm. P300 detection was occasionally difficult in epileptic children. Mean P300 latency in epileptic children (375 +/- 39.7 msec) was significantly prolonged compared with that in normal control children. (355 +/- 39.1 msec). P300 latencies in the children with symptomatic partial epilepsies were prolonged and were not recognized to be shortened with age. In the idiopathic partial epilepsies of 5 to 12 years of age, P300 latencies showed almost the same values with those in the normal children. However, in the idiopathic partial epilepsies of 13 to 15 years of age, P300 latencies were significantly prolonged compared with those in normal children and there were no difference in P300 latencies with other epileptic syndromes. P300 latencies in idiopathic generalized epilepsies showed intermediate values between that in symptomatic partial epilepsies and idiopathic partial epilepsies. Each epileptic syndrome showed different developments in P300 latencies with age. This results suggests that the development and the disturbance of cognitive functions differ among the epileptic syndromes. PMID- 1904254 TI - [Negative myoclonus; a simple partial seizure]. AB - Negative myoclonus in a 4-year-old boy was analyzed by polygraphic study, which lead to the diagnosis of simple partial seizure. He had irregularly trembling movements of right upper limb when he held some objects with his right hand. There were also coarse trembling movements in his body and lower limbs while sitting or standing. Polygraphic recording showed that the involuntary movements were caused by intermittent inhibition of muscle contraction associated with electrical silence on EMG and spikes in the left central area on EEG. PMID- 1904255 TI - Effects of epidermal growth factor on growth response, morphology, and invasive potential of human endometrial carcinoma cell line RL95-2. AB - Exposure of RL95-2 human endometrial adenosquamous carcinoma cells of early passage (less than 30 passages) and late passage (greater than 250 passages) to epidermal growth factor (EGF) resulted in density- and concentration-dependent effects. At low seeding density, EGF (20 nM) inhibited the growth of early passage cells, whereas at high seeding density, 4.98 nM and 20 nM concentrations of EGF stimulated their growth. Furthermore, the growth of late passage cells was stimulated by 0.0166 nM EGF and inhibited by 4.98 nM and 20 nM EGF at both seeding densities. EGF (20 nM) caused marked morphological changes of both passages at the low seeding density. Inhibition of invasion of both passages through Matrigel-coated filters was seen at low seeding density, while at the high seeding density, EGF enhanced invasiveness. At high seeding density, EGF stimulated an increase in urokinase type plasminogen activator activity, which may have augmented the ability of cells to degrade the extracellular matrix. In addition, the ability of high seeding density cells of both passages to adhere to matrigel after EGF treatment correlated with invasiveness. PMID- 1904257 TI - Special hospitals. A collective responsibility. PMID- 1904256 TI - [Obstructive urethral disease in neonates]. AB - In the past eight years, we observed 23 cases of neonatal urethral obstruction: 15 posterior urethral valves, one urethral polyp, two urethral diverticula, one penile urethra hypoplasia, two syringoceles, one scafoid urethra, one urethral agenesis in Prune Belly syndrome. In most cases a prenatal diagnosis of uropathy had been made by ultrasonography that allowed a faster diagnosis and possibly a long-term better prognosis in those patients in which early treatment reduced postnatal damage. In all patients endoscopic resection was performed under direct view. In 14 of them endoscopic treatment solved the problem, while further surgery on the upper urinary tract was needed in the others. We had no stenotic nor other-short and medium-term complications. The incidence of renal dysplasia is high with posterior urethral valves, while upper urinary tract damages are sensibly less frequent with more distal obstructions. PMID- 1904258 TI - Special hospitals. Nursing's last frontier? PMID- 1904259 TI - North of England focus. Crossing regional boundaries. PMID- 1904260 TI - Diabetes: a number of common questions on its management. PMID- 1904261 TI - The smear test: women's views. PMID- 1904262 TI - Assertiveness and clinical practice. PMID- 1904263 TI - ECG file. Q wave changes after infarction. PMID- 1904264 TI - Valid points. PMID- 1904265 TI - Mountain excitement. PMID- 1904267 TI - Special job focus. PMID- 1904266 TI - Legal notes. Watch your back. PMID- 1904269 TI - Experience with salvage regimens at M.D. Anderson Hospital. AB - With the intent of using active regimens in the front-line setting, new combinations of chemotherapy have been tested as salvage treatment in lymphoma patients at M.D. Anderson Hospital. Combinations based on ifosfamide plus etoposide, including IMVP-16 (ifosfamide/methotrexate/etoposide) and MIME (methyl GAG/ifosfamide/methotrexate/etoposide) resulted in overall and complete responses (CRs) of 60 and 25%, respectively. Long-term follow-up of MIME indicates a 25% cure rate in intermediate-grade lymphoma patients who achieve CR. The in vitro synergism of platinum and high-dose cytarabine recently has been confirmed clinically. A study is currently under way to evaluate the effect of integrating MINE (mesna/ifosfamide/mitoxantrone/etoposide) and ESHAP (etoposide/methyl prednisolone/cytarabine/platinum) into one protocol. PMID- 1904268 TI - Treatment of refractory pure red cell aplasia with cyclosporine A: disappearance of IgG inhibitor associated with clinical response. AB - Remissions were obtained in 6/9 evaluable patients with pure red cell asplasia (PRCA) refractory to other immunosuppressive agents who were treated with cyclosporine A (CsA). Four of these patients have remained in continuous remission off all treatment for 4-19 months. Another patient who stopped CsA abruptly relapsed, but responded to reinstitution of therapy. The sixth patient died of a cerebrovascular accident while in remission on a low dose of CsA. Acute side effects were minimal and were responsive to dose reduction. One patient developed a lymphoma while in an unmaintained remission, and one patient who did not respond to CsA was found to have a lymphoma approximately a year after stopping treatment. In vitro studies of autologous erythroid progenitors in a patient with an IgG inhibitor of erythropoiesis showed a reduction of autoantibody associated with the response to CsA. The antigen to which this inhibitor is directed was expressed only during the marrow erythroid burst forming unit (BFU-E) period of erythroid differentiation. CsA can induce sustained remissions in cases of PRCA refractory to other multiple agents, and these remissions may be associated with a reduction in autoantibody to erythroid progenitor cells. Further studies of patients with PRCA who respond to CsA may lead to an improved understanding of this disorder. PMID- 1904271 TI - Body fat in lean and overweight women estimated by six methods. AB - Body fat content of seven lean women (body mass index (BMI) 20.6 (SD 1.8) kg/m2) and seven overweight women (BMI 31.1 (SD 3.3) kg/m2) was estimated by six different methods: underwater weighing (UWW), body-water dilution (BWD), whole body counting (40K), skinfold thickness (SFT), bioelectrical impedance (BEI) and magnetic resonance imaging (MRI). Using UWW as the reference method, the differences between percentage fat by each other method and the percentage fat by UWW were calculated for each subject. The mean difference was lowest for SFT and highest for BWD. MRI showed the lowest variability in individual results, and 40K the highest. 40K and BWD methods used in combination gave better agreement with UWW results than either 40K or BWD methods alone. There was a weak negative correlation between the difference from the UWW results and percentage fat in the SFT measurements, but not in the BWD, 40K, BEI or MRI measurements, suggesting that for these methods the assumptions involved produced no greater inaccuracy in the overweight women than in the lean women. In all subjects the BEI offered little improvement over the traditional SFT measurements. The agreement between MRI and UWW estimates in both lean and overweight women suggests that MRI may be a satisfactory substitute for the more established methods of body fat estimation in adult women. PMID- 1904270 TI - Digestive development of the early-weaned pig. 1. Effect of continuous nutrient supply on the development of the digestive tract and on changes in digestive enzyme activity during the first week post-weaning. AB - Gastric intubation was adopted to examine the effect of continuous nutrient supply on digestive development of the pig during the immediate post-weaning period. The 14 d-weaned animals were slaughtered at 3, 5 and 7 d post-weaning (3W, 5W and 7W respectively) and the suckled animals were slaughtered at 14 and 22 d of age (14SR and 22SR respectively). The weight of the pancreas (g/kg bodyweight) was significantly greater (P less than 0.05) in the 5W and 7W groups, as was the weight of large intestine (g/kg) in all weaned groups (P less than 0.01) compared with sow-reared pigs. The stomach weight (g/kg) tended to be greater in the weaned groups. Weaning, in conjunction with a continuous nutrient supply, did not significantly alter the time-related changes in the weight of the small intestine (SI) or the SI mucosa, although both variables tended to be lowest in the 3W group. However, there was a 20% reduction in the protein content of the mucosa within the first 3 d post-weaning (P less than 0.01) which persisted during the 7 d experimental period. Lactase, (beta-galactosidase; EC 3.2.1.23) activity (mumol/g protein and mol/d) of the 7W group was reduced to approximately 40% of the 22SR value. Hence, continuous nutrient supply may have delayed, but did not prevent, the loss of lactase activity at weaning. The activity of sucrase (sucrose-alpha-glucosidase; EC 3.2.1.48) was significantly higher in 22SR compared with 14SR animals. Sucrase activity in weaned pigs was intermediate to the values for sow-reared pigs whereas maltase (alpha glucosidase; EC 3.2.1.20) and glucoamylase (glucan 1,4-alpha-glucosidase; EC 3.2.1.3) were significantly increased in relation to their sow-reared counterparts. Continuous nutrient supply did not prevent the reduction in villous height and the crypt hypertrophy associated with weaning. The results of the present study suggest that there may be some degree of interaction between nutrient intake and gut development during the immediate post-weaning period but that there is also a component of the adaptive response which is independent of nutrient intake. They confirm the rapid substrate induction of the brush-border glucoamylases and indicate the importance of considering total as well as specific enzyme activity for satisfactory interpretation of changes in digestive function. PMID- 1904272 TI - Binding of ethidium to the nucleosome core particle. 1. Binding and dissociation reactions. AB - We have examined binding properties of and dissociation induced by the intercalating dye ethidium bromide when it interacts with the nucleosome core particle under low ionic strength conditions. Ethidium binding to the core particle results in a reversible dissociation which requires the critical binding of 14 ethidium molecules. Under low ionic strength conditions, dissociation is about 90% completed in 5 h. The observed ethidium binding isotherm was corrected for the presence of free DNA due to particle dissociation. The corrected curve reveals that the binding of ethidium to the core particle itself is a highly cooperative process characterized by a low intrinsic binding constant of KA = 2.4 X 10(4) M-1 and a cooperativity parameter of omega = approximately 140. The number of base pairs excluded to another dye molecule by each bound dye molecule (n) is 4.5. Through the use of a chemical probe, methidiumpropyl-EDTA (MPE), we have localized the initial binding sites of ethidium in the core particle to consist of an average of 27 +/- 4 bp of DNA that are distributed near both ends of the DNA termini. MPE footprint analysis has also revealed that, prior to dissociation, the fractional population of core particles which bind the dye (f) may be as low as 50%. Comparison of the binding and dissociation data showed that the cooperative maximum of the binding curve occurred at or near the critical value, i.e., at the point where dissociation began. The data were used to generate a detailed model for the association of ethidium with chromatin at the level of the nucleosome. PMID- 1904273 TI - Synthesis and biological evaluation of a fluorescent analogue of folic acid. AB - A fluorescein derivative of the lysine analogue of folic acid, N alpha-pteroyl-N epilson-(4'-fluoresceinthiocarbamoyl)-L-lysine (PLF), was synthesized as a probe for dihydrofolate reductase (DHFR) and a membrane folate binding protein (m-FBP). Excitation of PLF at 282 nm and at 497 nm gave a fluorescence emission maximum at 518 nm. Binding of PLF to human DHFR or human placental m-FBP results in approximately a 20-fold enhancement in the magnitude of the fluorescence emission, suggesting that the ligand interacts with a hydrophobic region on these proteins. Additional evidence suggests that an energy transfer may occur between the pteridine and the fluorescein moieties. PLF binds to the active site of human DHFR since methotrexate (MTX) competes stoichiometrically and the denatured enzyme in the presence of PLF did not exhibit fluorescent enhancement. The dissociation constant for the fluorescein derivative with respect to human DHFR is 115 nM as compared to 111 nM for folic acid. The Ki value for the competitive inhibition of human DHFR by the fluorescent analogue of folic acid is 2.0 microM compared to 0.48 microM for folic acid. PLF was reduced to N alpha-(7,8 dihydropteroyl)-N epilson-(4'-fluoresceinthiocarbamoyl)-L-lysine (H2PLF) and assayed by the enzymatic conversion to the tetrahydro derivative. The Km value for human DHFR for the dihydrofolate analogue is 2.0 microM. The KD value for H2PLF to human DHFR is 47 nM as compared to 44 nM for dihydrofolate. The KD values for both H2PLF and PLF indicate that the fluorescein moiety does not significantly affect folate binding in enzyme binary complexes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1904274 TI - Solution conformation of a peptide fragment representing a proposed RNA-binding site of a viral coat protein studied by two-dimensional NMR. AB - The first 25 amino acids of the coat protein of cowpea chlorotic mottle virus are essential for binding the encapsidated RNA. Although an alpha-helical conformation has been predicted for this highly positively charged N-terminal region [Argos, P. (1981) Virology 110, 55-62; Vriend, G., Verduin, B. J. M., & Hemminga, M. A. (1986) J. Mol. Biol. 191, 453-460], no experimental evidence for this conformation has been presented so far. In this study, two-dimensional proton NMR experiments were performed on a chemically synthesized pentacosapeptide containing the first 25 amino acids of this coat protein [Ten Kortenaar, P. B. W., Kruse, J., Hemminga, M. A., & Tesser, G. I. (1986) Int. J. Pept. Protein Res. 27, 401-413]. All resonances could be assigned by a combined use of two-dimensional correlated spectroscopy and nuclear Overhauser enhancement spectroscopy carried out at four different temperatures. Various NMR parameters indicate the presence of a conformational ensemble consisting of helical structures rapidly converting into more extended states. Differences in chemical shifts and nuclear Overhauser effects indicate that lowering the temperature induces a shift of the dynamic equilibrium toward more helical structures. At 10 degrees C, a perceptible fraction of the conformational ensemble consists of structures with an alpha-helical conformation between residues 9 and 17, likely starting with a turnlike structure around Thr9 and Arg10. Both the conformation and the position of this helical region agree well with the secondary structure predictions mentioned above. PMID- 1904275 TI - Fluorescence polarization and low-temperature absorption spectroscopy of a subunit form of light-harvesting complex I from purple photosynthetic bacteria. AB - Measurements of polarized fluorescence and CD were made on light-harvesting complex 1 and a subunit form of this complex from Rhodospirillum rubrum, Rhodobacter sphaeroides, and Rhodobacter capsulatus. The subunit form of LH1, characterized by a near-infrared absorbance band at approximately 820 nm, was obtained by titration of carotenoid-depleted LH1 complexes with the detergent n octyl beta-D-glucopyranoside as reported by Miller et al. (1987) [Miller J. F., Hinchigeri, S. B., Parkes-Loach, P. S., Callahan, P. M., Sprinkle, J. R., & Loach, P. A. (1987) Biochemistry 26, 5055-5062]. Fluorescence polarization and CD measurements at 77 K suggest that this subunit form must consist of an interacting bacteriochlorophyll a dimer in all three bacterial species. A small, local decrease in the polarization of the fluorescence is observed upon excitation at the blue side of the absorption band of the B820 subunit. This decrease is ascribed to the presence of a high-energy exciton component, perpendicular to the main low-energy exciton component. From the extent of the depolarization, we estimate the oscillator strength of the high-energy component to be at most 3% of the main absorption band. The optical properties of B820 are best explained by a Bchl a dimer that has a parallel or antiparallel configuration with an angle between the Qy transition dipoles not larger than 33 degrees. The importance of this structure is emphasized by the results showing that core antennas from three different purple bacteria have a similar structure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1904276 TI - Formation of difluorothionoacetyl-protein adducts by S-(1,1,2,2-tetrafluoroethyl) L-cysteine metabolites: nucleophilic catalysis of stable lysyl adduct formation by histidine and tyrosine. AB - 19F NMR spectroscopy was used in conjunction with isotopic labeling to demonstrate that difluorothionoacetyl-protein adducts are formed by metabolites of the nephrotoxic cysteine conjugate S-(1,1,2,2-tetrafluoroethyl)-L-cysteine (TFEC). To determine which amino acid residues can be involved in adduct formation, the reactivity of TFEC metabolites with a variety of N-acetyl amino acids was also investigated. An N alpha-acetyl-N epsilon (difluorothionoacetyl)lysine (DFTAL) adduct was isolated and characterized by 19F and 13C NMR spectroscopy and mass spectrometry. N alpha-Acetylhistidine and N acetyltyrosine were found to act as nucleophilic catalysts to facilitate the formation of both the protein and DFTAL adducts. Adduct formation was greatly reduced when lysyl-modified protein was used as the substrate, indicating that lysyl residues are primary sites of adduct formation. However N alpha acetyllysine, at concentrations of greater than 100-fold in excess compared to protein lysyl residues, was not effective in preventing binding of metabolites to protein. Therefore, nucleophilic catalysis at the surface of the protein may be an important mechanism for the binding of TFEC metabolites to specific lysyl residues in protein. TFEC metabolites were very reactive with the thiol nucleophiles glutathione and N-acetylcysteine. However, the predicted difluorodithioesters could not be isolated. Both stable difluorothioacetamide and less stable difluorodithioester protein adducts may play a role in TFEC-mediated nephrotoxicity. PMID- 1904278 TI - Effects of detergents on the sulfation of chondroitin sulfate by sulfotransferase from chicken embryo epiphyseal cartilage. AB - Homogenates of chicken embryo epiphyseal cartilage were prepared in buffered saline. The bulk of the sulfotransferase was found in the supernatant. However, small amounts of sulfotransferase were consistently found in the particulate fraction. Detergents (Triton X-100 and C12E8) added to the incubation mixture activated the sulfation of exogenous sulfate acceptor by the particulate fraction, whereas detergent treatment during homogenization increased sulfotransferase activity in the supernatant at the expense of that in the particulate fraction. Since sulfotransferase activities of the supernatant and particulate fractions had similar properties concerning specificity, affinity for chondroitin with different degrees of sulfation, thermal stability and activation by protamine, we conclude that the same enzyme is present in both fractions and that detergent activates indirectly, by releasing it to the medium. PMID- 1904277 TI - Inhibition of the oxidation of hydroxyl radical scavenging agents after alkaline phosphatase treatment of rat liver microsomes. AB - Treatment of rat liver microsomes with alkaline phosphatase results in a loss in the FMN but not the FAD flavin prosthetic group of NADPH-cytochrome P-450 reductase (Taniguchi, H. and Pyerin, W. (1987) Biochim. Biophys. Acta 912, 295 307). Experiments were carried out to evaluate the effect of preventing electron transfer from the FADH2 to FMN component of the reductase, and subsequent mixed function oxidase activity, on reduction of ferric chelates, production of H2O2, and the generation of .OH-like species by microsomes. Treatment with alkaline phosphatase was confirmed to decrease NADPH-cytochrome c, but not NADPH ferricyanide, reductase activity by microsomes and by purified NADPH cytochrome P 450 reductase. The oxidation of hydroxyl radical scavenging agents by microsomes and reductase was decreased by the alkaline phosphatase treatment in accordance with the decline in cytochrome c reductase activity. This decrease in hydroxyl radical production occurred in the presence of various ferric chelate catalysts. Rates of microsomal reduction of the ferric chelates were also inhibited after alkaline phosphatase treatment. Production of H2O2 was decreased in accordance to the fall in cytochrome c reductase activity and .OH production. Rates of H2O2 production appeared to be rate-limiting for the overall generation of .OH as the addition of an external H2O2-generating system stimulated .OH production as well as prevented the decline in .OH production caused by the alkaline phosphatase treatment. These results suggest that both the FAD and FMN flavin prosthetic groups of the reductase contribute towards the reduction of various ferric chelates. However, loss of the FMN component and activities dependent on electron transfer from this prosthetic group result in a decrease in H2O2 production, which appears to be responsible for the decline in the generation of .OH-like species by microsomes after treatment with alkaline phosphatase. PMID- 1904280 TI - Development of a radioimmunoassay for RX77368 (pGlu-His-3,3-dimethyl proline amide)--a stable analogue of thyrotrophin releasing hormone (TRH). AB - The recent interest in RX77368 for the treatment of Motor Neurone Disease (MND) has led to the requirement for an assay (RIA) capable of detecting the peptide at low levels in plasma. Several drug conjugates were prepared in which RX77368 was covalently linked to larger proteins, e.g. bovine serum albumin, keyhole limpet haemocyanin or bovine thyroglobulin, the best yield being obtained with the bis diazotized benzidine reaction (BDB) linking RX77368 to KLH. The latter conjugate was injected into sheep and ultimately produced an antibody of sufficiently high titre to be used. This combined with an iodinated radiolabel formed the basis of the radioimmunoassay. Cross-reactivity studies using similar analogues and RX77368 metabolites showed that the antibody was specific for RX77368. The greatest cross-reactivity was exhibited by the pGlu-His-monomethylProNH2 peptide (RX74355), but, not being a natural metabolite, this did not interfere with the assay. The RIA was used to measure RX77368 in MND patients in a recent clinical study, where RX77368 was administered both by the intravenous and oral routes. High plasma concentrations of RX77368 were found in the patients given intravenous drug by infusion. The oral route exhibited much lower levels, but had a sustained duration of action of up to 12 h. PMID- 1904279 TI - The influence of pH on cystine and dibasic amino acid transport by rat renal brushborder membrane vesicles. AB - The uptake of cystine and lysine by rat renal brushborder membrane vesicles was examined at various intravesicular and extravesicular hydrogen ion concentrations to discern whether ionic species are determinants of specificity for the shared transport system and whether hydrogen ion gradients play a role in determining uptake values. When intravesicular and extravesicular pH are identical, the highest uptake of cystine occurred at pH 7.4, with lesser uptake at pH 6.0 and 8.3. Since cystine is electroneutral at pH 6.0 and 90% anionic at pH 8.3, it appears that neither form of the amino acid is a preferred species for transport. A similar relationship between pH and uptake occurs for lysine, which is cationic at pH below 8.5. This suggests that pH affects the functioning of the membrane carrier system independent of ionic species of the substrate. There is no apparent relationship of cystine uptake to hydrogen ion gradients across the membrane. Over the range of extravesicular pH studied, optimal cystine uptake occurred whenever the intravesicular pH was 7.4. Competitive interactions between unlabeled amino acids and labeled cystine were not affected by the extravesicular pH and, therefore, did not seem determined by the ionic species of cystine. PMID- 1904281 TI - Age-related alterations in prolactin secretion by individual cells as assessed by the reverse hemolytic plaque assay. AB - The objectives of this study were to determine: 1) if lactotropes from old rats, compared to those from young rats, secrete a greater amount of prolactin (PRL) per cell, 2) if the percentage of pituitary cells secreting PRL changes with age; and 3) how estradiol (E2), dopamine (DA), or thyrotropin-releasing hormone (TRH), or the combination of these factors influences both of these parameters in old rats. To meet these objectives we used the reverse hemolytic plaque assay (RHPA), because this method allows us to determine both the percentage of pituitary cells secreting prolactin during the experimental period and the amount of hormone released by each secreting pituitary cell. These parameters were measured in young (2-3 mo old) or old (17-19 mo old) female Sprague-Dawley rats. Animals were ovariectomized (OVX) for 10 days or OVX for 1 wk and then treated with E2 for 3 days. Rats were killed, anterior pituitaries were removed, and cells were enzymatically dispersed and prepared for use in the RHPA. Pituitary cells were treated in vitro with vehicle, DA, or PRL, old OVX and E2-treated rats exhibited a greater percentage of secretory cells than young at both 1 and 2 h of incubation. Administration of E2 increased the percentage of cells secreting PRL in both young and old rats. DA reduced the percentage of cells secreting PRL at the highest dose tested (10(-5) M) regardless of age or E2 status following incubation for 1 h.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1904282 TI - Effect of DMBA on the expression of prolactin receptors and IGF1 genes in rat mammary gland. AB - Prolactin receptor and IGF1 gene expression were measured in mammary glands from Sprague-Dawley rats at different times (10, 30; and 58 d) after administration of a single dose of 15 mg dimethylbenz(a)-anthracene (DMBA) per os at 55 d of age, and in DMBA-induced mammary tumors appearing in these rats at approximately 2 months after DMBA administration; The relative gene expression of prolactin receptor and insulin-like growth factor (IGF1) mRNAs was measured by hybridization to Northern blots prepared from pools of tissue. The probes used were 32P-labelled cDNAs specific to the extracellular domain of the receptor (E probe), common to all forms, and a probe specific to the intracellular position of the long form of the receptor (I probe), a human IGF1 probe, and chicken beta actin probe, to correct for loss of tissue and different metabolic activity of the tissues. Hybridization with the prolactin receptor probes revealed bands at 2.5, 3; and 5.5 kb hybridizing with the long form of the receptor and a more intense band at 1.8 kb that corresponded to the short form of the receptor. There were no changes in the relative expression of prolactin receptor mRNAs in the mammary gland of control (oil-treated) or DMBA-treated rats, although there was a gradual diminution of expression with increasing age of the animals. In contrast, in DMBA-induced mammary tumors, there was a marked increase in the relative expression of prolactin receptor mRNAs with, however, no modification in the relative proportion of short and long forms.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1904283 TI - Expression of c-jun during macrophage differentiation of HL-60 cells. AB - Cellular transcription factors are important in the regulation of cellular genes. Recent studies have indicated that a class of cellular genes known as early response genes are important in the control of cellular growth properties. Two of these genes, c-jun and c-fos, play an important role in the control of cellular differentiation. Because the acute myelogenous leukemia cell line, HL-60, is capable of differentiating to either macrophages or granulocytes, it provides a good model to understand differential gene expression. To determine if the modulation of c-jun was important in the differentiation of HL-60 cells to either macrophages or granulocytes, expression of c-jun mRNA was determined by Northern analysis at various times following treatment with a variety of differentiating agents, including 12-tetradeconyl-phorbol 13-acetate (TPA), retinoic acid (RA), dimethyl sulfoxide (DMSO), or 1,25 dihydroxyvitamin D3 [1,25 (OH)2 D3]. Both TPA and 1,25(OH)2D3, which induce HL-60 cells to differentiate to macrophages, resulted in marked increases in c-jun mRNA; while RA and DMSO, which induce HL-60 cells to differentiate to granulocytes, did not greatly alter c-jun mRNA expression. HL-60 cell lines resistant to macrophage differentiation after exposure to either 1,25(OH)2D3 or TPA did not result in increases in c-jun mRNA. These results suggest that elevation of c-jun mRNA in HL-60 cells correlated temporally with differentiation to macrophages. Thus, c-jun may be a critical cellular transcription factor involved in macrophage differentiation. PMID- 1904284 TI - Inhibitor of the thrombin time in systemic amyloidosis: a common coagulation abnormality. AB - Patients with primary systemic amyloidosis (AL) often experience bleeding, and we report a newly recognized coagulation abnormality in AL. Of 103 patients with primary systemic AL studied over 2 years, 41 had prolongation of the thrombin time (range, 25 to 46 seconds; normal, less than 22 seconds) and reptilase time (range, 17 to 39 seconds; normal, 14 to 16 seconds). The fibrinogen from the plasma of 36 patients was precipitated by beta-alanine and diluted to a concentration of approximately 200 mg/dL. The thrombin times of the precipitated fibrinogens were normal in 34 patients, implying that an inhibitor was responsible for the abnormal tests. The addition of patient fibrinogen-free plasma to normal plasma prolonged the thrombin times, and this result confirmed the presence of an inhibitor. The inhibitor is more likely to be present in patients with nephrotic syndrome (20 of our patients) and congestive heart failure (six). A circulating monoclonal protein (24 patients), the presence of amyloid liver involvement (eight), and the presence of amyloid neuropathy (nine) were not predisposing factors. Only one patient had deficiency of factor X. We conclude that inhibition of fibrinogen conversion to a fibrin clot rather than dysfibrinogenemia is the cause of the prolonged thrombin time in primary systemic AL. PMID- 1904285 TI - Cytokine influence on killing of fresh chronic lymphocytic leukemia cells by human leukocytes. AB - The feasibility of combining the Lym-1 monoclonal antibody (MoAb) with interferon gamma (IFN-gamma) in the treatment of chronic lymphocytic leukemia (CLL) was evaluated. We used an in vitro tumor lysis model that incorporated fresh CLL cells from 21 different patients as targets for two distinct normal human leukocyte effector subsets, neutrophils, and peripheral blood mononuclear cells (PBMCs). Lym-1 antigen (Lym-1-Ag) expression varied greatly and did not correlate with the expression of other CLL-associated antigens such as CD5, CD19, or HLA DR. CLL cells were not lysed by neutrophils alone or with IFN-gamma in the absence of Lym-1. Neutrophil Lym-1-dependent cytotoxicity (ADCC) in the absence of IFN-gamma was weak and inconsistent. IFN-gamma exposure induced MoAb-dependent lysis of 80% of 21 CLL targets and resulted in an eightfold augmentation of neutrophil ADCC against the remainder. Cytotoxicity correlated directly and positively with Lym-1-Ag expression. Confirmation of the need for interaction between neutrophil IgG Fc receptors (Fc gamma Rs) and the Fc portion of the Lym-1 MoAb was obtained by demonstrating that purified Staphylococcus aureus Protein A (SpA) inhibited ADCC. IFN-gamma exposure caused no consistent alternations in Lym 1-Ag expression on CLL cells so that target antigen upregulation was unlikely to account for augmentation of neutrophil ADCC. PBMCs alone, exposed to interkeukin 2 (IL-2) or IFN-gamma, or with Lym-1 in the presence or absence of IL-2 or IFN gamma were unable to lyse CLL targets. PBMCs were able to kill Raji Burkitt lymphoma cells in conjunction with Lym-1, so their ability to interact with Lym-1 coated targets and their lytic functions appeared intact. These results emphasize the importance of examining fresh tumor cells with different leukocyte effector subsets before designing a clinical trial that combines a therapeutic MoAb with a cytokine. PMID- 1904286 TI - Cost effectiveness of incremental programmes for lowering serum cholesterol concentration: is individual intervention worth while? AB - OBJECTIVE: To evaluate the relative cost effectiveness of various cholesterol lowering programmes. DESIGN: Retrospective analysis. SETTING: Norwegian cholesterol lowering programme in Norwegian male population aged 40-49 (n = 200,000), whose interventions comprise a population based promotion of healthier eating habits, dietary treatment (subjects with serum cholesterol concentration 6.0-7.9 mmol/l), and dietary and drug treatment combined (serum cholesterol concentration greater than or equal to 8.0 mmol/l). MAIN OUTCOME MEASURE: Marginal cost effectiveness ratios--that is, the ratio of net treatment costs (cost of treatment minus savings in treatment costs for coronary heart disease) to life years gained and to quality of life years (QALYs) saved. RESULTS: The cost per life year gained over 20 years of a population based strategy was projected to be 12 pounds. For an individual strategy based on dietary treatment the cost was about 12,400 pounds per life year gained and 111,600 pounds if drugs were added for 50% of the subjects with serum cholesterol concentrations greater than or equal to 8.0 mmol/l. CONCLUSIONS: The results underline the importance of marginal cost effectiveness analyses for incremental programmes of health care. The calculations of QALYs, though speculative, indicate that individual intervention should be implemented cautiously and within more selected groups than currently recommended. Drugs should be reserved for subjects with genetic hypercholesterolaemia or who are otherwise at very high risk of arteriosclerotic disease. PMID- 1904287 TI - Course of brittle diabetes: 12 year follow up. AB - OBJECTIVE: To determine the course of brittle diabetes. DESIGN: 12 year follow up of patients identified in 1977-9 as having brittle diabetes; retrospective review of the case notes. SETTING: Nottingham health district. SUBJECTS: 25 brittle diabetic patients were identified in 1979-9; 11 (five men) had three or more admissions with ketoacidosis between June 1977 and 1979 and 14 (eight men) had three or more attendances at the accident and emergency department with hypoglycaemia in 1978. Two controls from our diabetic register were matched to each patient for age, sex, and duration of diabetes. MAIN OUTCOME MEASURES: Frequency of ketoacidosis and severe hypoglycaemia in the 12 years after ascertainment; diabetic control and complications in 1988-90; retrospective attribution of the cause of brittleness. RESULTS: Patients with recurrent ketoacidosis had had a median (range) of 28 (8-67) episodes. One man died of a cerebral tumour but five of the surviving nine patients had not been admitted in the past two years, although diabetic control remained poor (median haemoglobin A1 concentration 14%). Seven patients had pure hypoglycaemic brittleness, and five had also had eight or more admissions with ketoacidosis (mixed brittleness). Two died of uraemia within a year after ascertainment and two others in hypoglycaemic coma seven and 12 years later. Brittle diabetes was in most cases related to a specific situation, usually unhappiness at home or school. CONCLUSIONS: Brittle diabetes is often episodic and almost always related to stressful life circumstances. Once the underlying cause is removed it tends to improve. Recurrent hypoglycaemic brittleness of psychological origin has a poor prognosis. PMID- 1904288 TI - Battle of the clotbusters. PMID- 1904289 TI - Lithium intoxication. PMID- 1904290 TI - Fertility, pregnancies and offspring complications after bone marrow transplantation. AB - Hormonal assessment including luteotropic hormone (LH), follicle stimulating hormone (FSH), testosterone (T), oestradiol and sex hormone binding globulin was performed 1-6 years after allogeneic, syngeneic and autologous bone marrow transplantation in nine patients with severe aplastic anaemia (SAA) and 14 patients with haematological malignancy (HM). Among nine allografted SAA patients, seven aged less than 26 years showed normal gonadal function while two women above 26 years had premature ovarian failure. All eight female patients transplanted for HM had premature ovarian failure. Among six male patients transplanted for HM, four have elevated FSH but normal LH and T levels, while two have normal LH, FSH and T levels or elevated LH and FSH levels but decreased T levels, respectively. Three patients transplanted for SAA (two female, one male), but none of those transplanted for HM, parented four healthy children. A high incidence of offspring complications was noticed, including (i) persistence of fetal circulation syndrome, (ii) erythroblastosis fetalis, and (iii) prolonged newborn icterus. One female patient transplanted for SAA had an abortion in the 25th week of gestation. These observations confirm previous reports on recovery of fertility, mainly in younger patients transplanted for SAA; there was, however, an unexpectedly high incidence of pre-, peri- and postpartum complications in the offspring of bone marrow graft recipients. PMID- 1904291 TI - Maintenance of self tolerance in CD4+ T lymphocytes by antigen presentation on resting B cells--a hypothesis. AB - Self tolerance in the immune system is established by clonal deletion or induction of clonal anergy in immature lymphocytes. In addition, repair mechanisms for self tolerance working in the mature immune system may exist to take care of self-reactive lymphocytes eventually leaking through the central mechanisms. Two possible repair mechanisms for self tolerance, both capable of self/nonself discrimination, are discussed in this article. The first is the so called veto function, which works on CD8+ T cells. The second is a new hypothesis suggesting that CD4+ T cells may be anergized by recognizing antigen on self specific, anergic B cells. PMID- 1904292 TI - Effects of glibenclamide on cytosolic calcium concentrations and on contraction of the rabbit aorta. AB - 1. Using fluorometry of fura-2 and rabbit aortic strips, we studied the effects of glibenclamide (GLB), a sulphonylurea anti-diabetic drug and an inhibitor of opening of K+ channels, on cytosolic calcium concentrations ([Ca2+]i) and on force development. 2. Both high K(+)-depolarization and noradrenaline (NA) increased [Ca2+]i and force, in a concentration-dependent manner, in the presence of extracellular Ca2+ (1.25 mM). However, force development in relation to [Ca2+]i ([Ca2+]i-force relationship) observed with NA was much greater than that observed with K(+)-depolarization. 3. Pretreatment with GLB (10(-6)-10(-4) M) for 10 min partially inhibited, in a concentration-dependent manner, both [Ca2+]i elevation and the force development induced by 118 mM K(+)-depolarization or NA 10(-5) M in the presence of extracellular Ca2+. The [Ca2+]i-force relationship induced by both 118 mM K+ physiological salt solutions and by NA 10(-5) M in the GLB-treated strips overlapped that obtained in the non-treated strips, thereby suggesting that GLB has no effect on the Ca2(+)-sensitivity of the intracellular contractile apparatus. Only high concentrations (10(-4) M) of GLB decreased [Ca2+]i and the force, when applied after the force induced by 118 mM K+ PSS or NA 10(-5) M reached the maximum level. 4. In the absence of extracellular Ca2+, NA induced a transient increase in [Ca2+]i and in the force and these increases were inhibited when the vascular strips were pretreated with GLB for 10 min. The [Ca2+]i-force relationship obtained in the GLB-treated strips overlapped that in the non-treated ones. 5. An ATP-sensitive K+ channel opener, cromakalim (10-5M) reduced the increased [Ca2 + ]i and force induced by 25mm K+-depolarization and NA 10-SM. Subsequent application of GLB concentrationdependently reversed this relaxant effect of cromakalim on the NA-induced contraction (IC50 = 2x 10 7 M). Complete reversal of the effect was observed with 10IsM GLB. 6. We suggest that GLB inhibits both high K+-depolarization- and NA-induced contraction of the rabbit aorta, by decreasing [Ca2+]i and with no effect on the [Ca2+]i-force relationship. However, when NA-induced contractions were inhibited by a K+ channel opener, GLB reversed this inhibitory effect by inhibiting K+-channel opening and increasing [Ca2 +]. PMID- 1904294 TI - [Does spiralin has a cleavable N-terminal signal sequence?]. AB - The amino acid sequence of spiralin deduced from the nucleotide sequence of its gene was fictitiously shortened by 1 to 50 residues from each terminus and the compositions of both series of theoretical polypeptides were calculated. The two series of compositions thus obtained were compared to that of the purified protein, with the use of the Marchalonis and Weltman index (S delta Q). The results of this analysis, which permits the difficulty resulting from the blocking of the N-terminal amino acid to be overcome, show that spiralin is probably synthesized as a 241-residue precursor containing an N-terminal signal sequence cleaved close to cysteine-24. Since spiralin is acylated and since the sequence Val-Val-Ala-Cys24 shares some similarity with the consensus sequence of bacterial lipoprotein modification/processing site, the hypothesis of a cleavage just before cysteine-24 seems plausible. PMID- 1904293 TI - Bradykinin induces elevations of cytosolic calcium through mobilisation of intracellular and extracellular pools in bovine aortic endothelial cells. AB - 1. In the presence of 1.8 mM extracellular calcium, bradykinin (0.3 nM-100 nM) induced a biphasic elevation of intracellular calcium ([Ca2+]i) in bovine aortic endothelial cells, consisting of an initial, large transient component followed by a lower sustained component. 2. When endothelial cells were bathed in nominally calcium-free solution containing 0.5 mM EGTA, bradykinin induced only a transient elevation of [Ca2+]i: the magnitude of this was significantly smaller than that obtained in the presence of extracellular calcium and the sustained phase was abolished. In the continued presence of bradykinin, re-addition of extracellular calcium to achieve a level of around 1.8 mM resulted in the induction of a biphasic elevation of [Ca2+]i consisting of a large initial component followed by a lower sustained component. 3. In the presence of 1.8 mM extracellular calcium, caffeine (5 mM) induced a small elevation of [Ca2+]i. When endothelial cells were bathed in nominally calcium-free solution containing 0.5 mM EGTA, the caffeine-induced elevation of [Ca2+]i was almost completely abolished. 4. In the presence of 1.8 mM extracellular calcium, treatment of endothelial cells with the calcium influx blocker, nickel chloride (4 mM), had no effect on resting [Ca2+]i or on the magnitude of the bradykinin-induced initial transient elevation of [Ca2+]i but abolished the sustained component. 5. In the presence of 1 mM extracellular calcium, treatment with the calcium chelator EGTA (2 mM; 1 min) had no effect on resting [Ca2+]i but the magnitude of the bradykinin-induced initial transient elevation of [Ca2+]i was significantly reduced. Increasing the exposure time or concentration of EGTA resulted in no further reduction in the magnitude of the bradykinin-induced transient component. 6. Treatment of endothelial cells with the putative inhibitor of intracellular calcium release, 3,4,5-trimethoxybenzoic acid 84diethylamino)octyl ester (TMB-8, 0.1 mM) increased resting [Ca21]i slightly but had no effect on the magnitude of the bradykinin-stimulated elevation of [Ca22ji. 7. These findings suggest that, in bovine aortic endothelial cells, the bradykinin-induced initial transient elevation of [Ca21]i is completely dependent upon release of calcium from intracellular stores and the sustained component is due to calcium influx. They further suggest the possible existence of two intracellular calcium pools, one which is rapidly depleted in the absence of extracellular calcium and a second which is resistant to such depletion. PMID- 1904295 TI - [Protein and enzymatic criteria for the characterization of phytopathogenic Pseudomonas fluorescens]. AB - Polyacrylamide gel electrophoresis of proteins was carried out to characterize eight bacterial strains belonging to the genus Pseudomonas. The sampling included three species (P. cichorii, P. viridiflava and P. syringae), with three pathovars for this last species (pv. pisi, pv. syringae, pv. tomato). Several molecular markers were evaluated: native proteins, denatured proteins, esterases, superoxide dismutases (SOD) and polyphenoloxidases (PPO). Each species or pathovar of Pseudomonas was clearly differentiated by esterase patterns. SOD, PPO and native protein patterns allowed strains of P. cichorii, P. viridiflava and P.s. pv. tomato also to be distinguished. Strains of P.s. pv. pisi and P.s. pv. syringae were identical for these criteria. Denatured protein patterns of these two pathovars and P. viridiflava were similar. PMID- 1904297 TI - [Solubilization, purification and molecular characterization of H2 histamine receptor from human tumoral gastric cells HGT-1]. AB - This communication reports the solubilization, the purification and the molecular characterization of the H2-histamine receptor from the cell line HGT-1 derived from a human gastric cancer. The receptor has been solubilized by Triton X100 and purified by gel filtration onto Sephacryl, affinity-chromatography (Sepharose famotidine) and high performance liquid chromatography (HPLC). The purified receptor specifically bound the H2 selective ligand 3H-methyltiotidine with a kD of 160 nM (vs 50 nM for the intact HGT-1 cell) and a maximal binding capacity of 14,000 pmol/mg protein which represents a 12,170-fold enrichment and a degree of purity of 98%. It is a glycoprotein of 70 kDa molecular mass containing N acetylglucosamine residues. PMID- 1904296 TI - [Demonstration of replication of daughter sporocysts in the natural development of Schistosoma japonicum]. AB - The participation of replicating sporocysts in the intramolluscal development of Schistosoma japonicum within its snail host Oncomelania hupensis is demonstrated by histological studies. Replicating sporocysts were observed in snails maintained under both standard and hibernation conditions. The demographic and epidemiological importance of the replication process within schistosomes is discussed comparatively. PMID- 1904298 TI - [Strategies for simultaneous control of the equilibrium and of the head position during the raising movement of a leg]. AB - The coordination between equilibrium control and the ability to maintain the position of given segments (head, trunk) was studied in standing subjects, instructed to raise one leg laterally at an angle of 45 degrees in response to a light. Two sources of light placed at eye level indicated the side on which the movement was to be performed. Two populations were compared: naive subjects and dancers. Two control strategies were identified. An "inclination" strategy was used by the naive subjects. This consisted of an external rotation of the body around the antero-posterior ankle joint axis; a counter-rotation of the head with respect to the trunk was observed, which ensured some stabilization in the horizontal plane of the interorbital line. A "translation" strategy was used by the dancers. Here the external rotation of the leg around the ankle joint was associated with a feed-forward counter-rotation of the trunk around the coxofemoral joint so that the horizontality of the interorbital line and the verticality of the trunk axis were maintained. This new coordination results from a long-term training and indicates that a new motor program has been elaborated. PMID- 1904299 TI - [Non-linear development of the frequency of swimming movements during ontogeny in rats]. AB - The choice of swimming as locomotor behaviour was justified by the fact that it could be elicited from birth to adult age. We have recorded electromyographic activities during swimming movements, on flexor muscles in front legs and hind legs (Spinodeltoidus and Gluteus superficialis). The mean frequency of activity of each limb during swimming, for animals aged from 0 to 20 or 30 days was then computed. The results showed an increase in frequency between 0 and 20 days from 1 to 4 Hz. This increase was not linear, but composed of different successive phases. After a first period of increase between 0 and 6 days (slope 0.25), for the hind limbs and the fore-limbs, we noted a plateau between 6 and 12 days during which the frequency was stable. This plateau was followed by another increase in the frequency values between 12 and 16 days (slope 0.30), followed by another plateau that corresponded to the adult frequency. PMID- 1904300 TI - [In vitro functional differentiation of hippocampal corticosterone receptors by mineralo- and glucocorticoids]. AB - Modulation of CA1 evoked electrophysiological properties (amplitude, latency, paired-pulse facilitation) by different concentrations of aldosterone (ALDO), spironolactone (SPI), and corticosterone (CT) was studied in hippocampal slice preparation from BALB/c mice. ALDO (5 nM) induced a prolonged increase of the population spike (PS) amplitude with a decrease of its latency and of the paired pulse facilitation. The same effect was observed with a solution of CT (0.5 nM) alone or combined with ALDO (0.5 nM), but no effect was observed with a solution of combined CT (0.5 nM) and SPI (500 nM). Implication of corticosteroid receptors in this response was discussed. PMID- 1904301 TI - [Brain protein synthesis in awake rats: equilibrium of L-methionine between plasma and direct precursor pool]. AB - After 1 hr. of continuous infusion of L-(35S)methionine the specific activities of L-methionine in plasma and tissue-free and tRNA-bound L-methionine in brain were in the same range. This result indicates that, under steady-state conditions, dilution of the precursor pool for protein synthesis (L-methionyl tRNA) by L-methionine derived from a source other than plasma can be considered as negligible. PMID- 1904302 TI - Results of ISIS-3 reported at ACC annual meeting. PMID- 1904303 TI - Lithium augmentation of fluoxetine in the treatment of OCD and major depression: a case report. PMID- 1904304 TI - Hexamethylmelamine (altretamine) activity as a single agent in previously untreated advanced ovarian cancer. PMID- 1904305 TI - Analysis of prognostic factors and survival in patients with ovarian cancer treated with second-line hexamethylmelamine (altretamine). AB - Hexamethylmelamine (altretamine, HMM) 260 mg/m2/day p.o. for 14 days followed by a 14-day drug-free interval was administered to 52 outpatients with advanced ovarian cancer who had previously been treated with chemotherapy. Prior to HMM, 92% (48/52) of these patients had received cisplatin and cyclophosphamide with or without doxorubicin. Two more patients received other cisplatin-based regimens. At the completion of HMM therapy, 15% (8/52) displayed no evidence of disease (NED). Of these eight patients, five are still alive 32 to 82 months after altretamine therapy (median follow-up of 46 months). At 41 months, one patient died of intercurrent illness with no clinical evidence of recurrence; the other two patients died of their disease at 21 and 31 months following HMM therapy. The median survival of the total group was 11 months: nine months for patients who did not respond to altretamine and 46+ months for patients with NED after altretamine (p less than 0.05). Intermittent oral administration of single-agent altretamine was well tolerated: eight patients reported moderate gastrointestinal symptoms, and only one patient reported severe gastrointestinal symptoms. Moderate neurologic toxicity was reported by five patients. No WBC fell below 2000 mm3 and platelet counts fell below 100,000 mm3 in only three patients; no patient experienced severe hematologic toxicity. In this series of patients, the overall response (15%) was comparable to or better than those reported for more toxic chemotherapeutic regimens. On the basis of these data and those reported by other investigators, HMM warrants consideration as a reasonable option in the management of recurrent or persistent ovarian cancer. PMID- 1904306 TI - Hexamethylmelamine: pharmacology and mechanism of action. AB - Several conclusions can be drawn from a review of HMM preclinical and clinical pharmacology data. The drug is extensively metabolized by animals and by man. The drug is well absorbed following oral administration to animals, but oral bioavailability is low due to first pass metabolism. Based on limited human data and more complete animal data, absorption of HMM following oral administration may be quite high in man. We do not yet know the oral bioavailability of HMM in patients, but again based primarily on animal studies, oral bioavailability is most likely low and variable due to extensive first pass metabolism. Systemic exposure to HMM and demethylated metabolites following oral administration varies greatly from patient to patient and is sometimes quite low. Most patients are, however, exposed to a substantial fraction of the administered dose when determined by urinary recovery of the total dose (based on parent drug and metabolites or total radioactivity) or by the total plasma AUC of parent drug and all metabolites. Systemic exposure to HMM following intravenous administration is clearly greater and less variable than following oral administration. An unresolved question is whether the highly variable and often low systemic exposure after oral administration compromise antitumor activity when compared to intravenous administration. A key issue is whether or not one accepts the hypothesis that metabolism is a prerequisite for antitumor activity. The metabolic activation studies do not rule out other mechanisms of HMM antitumor activity. Modest activity of HMM was observed after prolonged exposure to cells which did not metabolize the drug. However, most of the accumulated data are consistent with the metabolic activation hypothesis. Certainly HMM has clinical activity when administered by mouth. If metabolism is required, then exposure to the total dose (parent drug and metabolites) could be of significance even when exposure to HMM is low, since every demethylated metabolite must have come ultimately from the initial HMM demethylation. We do not know whether the initial metabolic reaction (occurring in the liver rather than in the tumor) provides sufficient exposure of tumor to reactive species. Specifically, does the variable HMM plasma AUC seen after oral administration lead to variable delivery of potentially reactive species to tumor (by rapid breakdown and/or further metabolism of MPMM before it leaves the gut and/or liver) or are quantities of MPMM delivered to tumor comparable to those delivered following intravenous administration. The issue of rate of MPMM formation compared to rate of breakdown and ultimate delivery to tumor has been noted by Judson and Rutty.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1904307 TI - Hexamethylmelamine (altretamine): early National Cancer Institute trials. PMID- 1904308 TI - Randomized comparison of hexamethylmelamine, adriamycin, cyclophosphamide (HAC) vs. cisplatin, adriamycin, cyclophosphamide (PAC) in advanced ovarian cancer: long-term results. PMID- 1904309 TI - A comparison of hexamethylmelamine (altretamine), cyclophosphamide, doxorubicin, and cisplatin (H-CAP) vs. cyclophosphamide, doxorubicin, and cisplatin (CAP) in advanced ovarian cancer. AB - We retrospectively compared the results of treatment with hexamethylmelamine (HMM), cyclophosphamide, doxorubicin, and cisplatin (H-CAP) to treatment results using cyclophosphamide, doxorubicin, and cisplatin (CAP) in patients with advanced ovarian cancer. The treatments were identical in dosage and schedule with the exception of the addition of HMM to one regimen. Fifty-five patients treated with H-CAP between August 1977 and March 1980 were compared with a subsequent group of 22 patients who received CAP between October 1984 and October 1987. Following 6 months of therapy, patients were restaged either with second look laparotomy or with clinical restaging. Fifty-three of 55 patients (96%) and 14/21 (67%) patients had objective responses to H-CAP and CAP respectively (p = 0.001). The pathologic complete response rate as determined by second-look laparotomy was higher in the patients who received H-CAP (35% vs. 19%). The median survival of patients receiving H-CAP is 47 months compared to 21 months for the CAP patients. In limited residual disease patients (maximum tumor diameter less than or equal to 3 cm), the median survival also favored the H-CAP treatment (101 months vs. 21 months, p = 0.002). The median time to progression was greater in patients receiving H-CAP vs. those receiving CAP (67 months vs. 16 months, p = 0.045). Treatment-related toxicity was similar for the two regimens. These findings suggest that the addition of HMM to CAP chemotherapy prolongs the median survival for patients with limited residual disease advanced ovarian cancer. PMID- 1904311 TI - The role of hexamethylmelamine in the management of ovarian cancer. AB - Hexamethylmelamine has been recognized as having useful single-agent activity for the treatment of ovarian cancer for the past 25 years, with some patients surviving disease-free for periods in excess of 12 years. Data from recently analysed and mature trials demonstrate that the addition of hexamethylmelamine to first-line combination chemotherapy results in significant improvements in survival compared to what is achieved with regimens of cisplatin and cyclophosphamide with or without doxorubicin. PMID- 1904310 TI - Hexamethylmelamine for the treatment of ovarian cancer--the Mount Sinai experience. AB - Two regimens were tested, CHAP I and CHAP II, the latter, a hexamethylmelamine dosage-intensive regimen, first as second line (salvage) therapy and then as primary therapy. Both produced the most successful results achieved in the Mount Sinai series up to the time of their introduction, when compared to their predecessor regimens: CAP, AP and P. In an overall interim comparison, CHAP II was significantly superior to historical AP and CAP as primary therapy, as was CHAP I vs. AP in several important subgroups compared as part of a randomized trial. CHAP II overall progression-free survival was improved in spite of added new sensitive test methods. Salvage therapy also improved markedly with the addition of intensive hexamethylmelamine. Several biological and treatment characteristics strongly influenced outcome, especially young age and adding hexamethylmelamine. Other possible factors included: poor tumor grade, poor performance status, and extent of surgical debulking, even to intermediate residual, 2-6 cm size [CHAP II only]; extensive (optimum) surgery [CHAP I only]. The hexamethylmelamine-containing regimens interact favorably with some of these factors, better than did the preceding regimens. Five-year follow-up analyses weakened slightly for extensive surgery, intermediate size and poorly differentiated tumors. It confirmed and strengthened several findings favoring CHAP I & II, the hexamethylmelamine-containing regimens. PMID- 1904312 TI - Ovarian cancer: new clinical approaches. PMID- 1904313 TI - Hexamethylmelamine use in the treatment of metastatic breast cancer. PMID- 1904314 TI - Hexamethylmelamine: activity in lymphoma and other tumors. AB - Hexamethylmelamine, an orally administered substituted melamine, has single agent activity in lymphoma (39% PR + CR), cervical cancer (28% PR), transitional carcinoma of the bladder (27% PR + CR), and Bilharzial bladder cancer (38% PR). Toxicity is mild and reversible and is manifested by myelosuppression, neurotoxicity and gastrointestinal toxicity. The potential role of hexamethylmelamine in combination chemotherapy in the diseases in which it has single agent activity is largely unexplored and should be investigated in clinical trials. PMID- 1904315 TI - Inhibition of protein synthesis enhances the lytic effects of tumor necrosis factor alpha and interferon gamma in cell lines derived from gynecological malignancies. AB - Few clinical responses have occurred in preliminary studies using the cytokines tumor necrosis factor alpha (TNF alpha) or interferon gamma (IFN gamma) in cancer patients. This may be related to the observation that many malignant cell lines are resistant to lysis by these cytokines in vitro. Resistance to lysis by TNF alpha or IFN gamma in many cells is controlled by a protein-synthesis-dependent mechanism, such that when protein synthesis is inhibited cells become sensitive to lysis by these cytokines. Because there is some evidence that TNF alpha and IFN gamma act through different lytic mechanisms and are opposed by different resistance mechanisms, we treated a panel of eight cell lines, five derived from human cervical carcinomas (ME-180, MS751, SiHa, HT-3, and C-33A) and three derived from ovarian carcinomas (Caov-3, SK-OV-3, and NIH: OVCAR-3) with both TNF alpha and IFN gamma to determine whether such combination treatment might maximize in vitro cell lysis. Our results showed that pretreatment with IFN gamma followed by exposure to TNF alpha in the presence of protein synthesis inhibitors increased lysis of seven of the eight cell lines above that seen with either TNF alpha or IFN gamma and inhibitors of protein synthesis. Only the cell line C-33A was resistant to lysis by TNF alpha and IFN gamma, when exposed to these agents both alone and in combination with protein synthesis inhibitors. Clinically, combining the cytokines TNF alpha and IFN gamma with protein synthesis inhibitors may maximize the in vivo lytic effects of these cytokines. PMID- 1904316 TI - Economic issues relating to access to medications. AB - Millions of uninsured, low-income workers (a disproportionate number of them black) are financially unable to obtain prescription drugs for treatment of conditions such as hypertension. As a result, funds spent to diagnose their underlying illnesses may be wasted, and they are likely to suffer complications that require much more costly care. The tendency for income levels to be inversely correlated with blood pressure means that those least able to pay for antihypertensive medication are those most susceptible to complications. Since current programs are inadequate to help most of these patients, there is a need for a joint initiative by the federal government and the pharmaceutical industry to fund programs to make medications easily accessible for the medically indigent population. PMID- 1904317 TI - Molecular cloning of a GTPase activating protein specific for the Krev-1 protein p21rap1. AB - The rap1/Krev-1 gene encodes a ras-related protein that suppresses transformation by ras oncogenes. We have purified an 88 kd GTPase activating protein (GAP), specific for the rap1/Krev-1 gene product, from bovine brain. Based on partial amino acid sequences obtained from this protein, a 3.3 kb cDNA was isolated from a human brain library. Expression of the cDNA in insect Sf9 cells resulted in high level production of an 85-95 kd rap1GAP that specifically stimulated the GTPase activity of p21rap1. The complete deduced amino acid sequence is not homologous to any known protein sequences, including GAPs specific for p21ras. Northern and Western blotting analysis indicate that rap1GAP is not ubiquitously expressed and appears most abundant in fetal tissues and certain tumor cell lines, particularly the Wilms' kidney tumor, SK-NEP-1, and the melanoma, SK-MEL 3, cell lines. PMID- 1904319 TI - [Treatment of stress incontinence using a combination of the parasympatholytics, hexadiphensulphonium and oxyphenonium and the spasmolytic, papaverine]. PMID- 1904318 TI - A novel arachidonic acid-selective cytosolic PLA2 contains a Ca(2+)-dependent translocation domain with homology to PKC and GAP. AB - We report the cloning and expression of a cDNA encoding a high molecular weight (85.2 kd) cytosolic phospholipase A2 (cPLA2) that has no detectable sequence homology with the secreted forms of PLA2. We show that cPLA2 selectively cleaves arachidonic acid from natural membrane vesicles and demonstrate that cPLA2 translocates to membrane vesicles in response to physiologically relevant changes in free calcium. Moreover, we demonstrate that an amino-terminal 140 amino acid fragment of cPLA2 translocates to natural membrane vesicles in a Ca(2+)-dependent fashion. Interestingly, we note that this 140 amino acid domain of cPLA2 contains a 45 amino acid region with homology to PKC, p65, GAP, and PLC. We suggest that this homology delineates a Ca(2+)-dependent phospholipid-binding motif, providing a mechanism for the second messenger Ca2+ to translocate and activate cytosolic proteins. PMID- 1904320 TI - The effect of dietary lipid on skin tumor promotion by benzoyl peroxide: comparison of fish, coconut and corn oil. AB - Fish or vegetable oils were fed during the promotion stage of a mouse skin carcinogenesis model in order to investigate the effects of dietary fat on tumor development. Two weeks after initiation with 10 nmol dimethylbenz[a]anthracene, SENCAR mice were divided into five groups and maintained on one of the following semipurified diets containing 10% total fat and varying the type of fat: 8.5% coconut oil (CT)/1.5% corn oil (CO); 1% menhaden oil (MO)/7.5% CT/1.5% CO; 4% MO/4.5% CT/1.5% CO; 8.5% MO/1.5% CO; or 10% CO. Promotion with twice-weekly applications of 40 mg benzoyl peroxide was begun 2 weeks later and continued for 52 weeks. No statistically significant differences in kcal food consumed or body weights were observed between diet groups. Papilloma latency, incidence and yield differed among the diet groups with the group fed the 8.5% CT/1.5% CO diet having the shortest latency and highest papilloma incidence and number. In addition, carcinoma latency and incidence was assessed and the first carcinoma appeared in the group fed 8.5% CT/1.5% CO after 20 weeks of benzoyl peroxide treatment; this group yielded the highest carcinoma incidence throughout the study. In comparison, the group fed the 10% CO diet had the longest latency period, and among the lowest papilloma and carcinoma incidence and fewest tumors. In parallel studies, ornithine decarboxylase activity, vascular permeability and hyperplasia were elevated in the epidermis of benzoyl peroxide-treated mice but the extent of the response did not correlate with the different rates of tumor formation observed among the diet groups. These data indicate that dietary fat modulates tumor promotion by benzoyl peroxide in this skin carcinogenesis model with the predominantly saturated fat diet producing the highest rates of papilloma and carcinogen formation and the polyunsaturated fat diet the lowest. PMID- 1904321 TI - Identification of (+) and (-) anti benzo[a]pyrene dihydrodiol epoxide-nucleic acid adducts by the 32P-postlabeling assay. AB - Purine deoxyribonucleoside 3'-phosphates were reacted with the (+)- and (-) enantiomers of the anti dihydrodiol epoxide of benzo[a]pyrene. Products from cis and trans opening of the epoxide ring were separated by HPLC and they were identified by comparison of their CD spectra with those known for the corresponding nucleoside adducts. Thereafter, the eight known benzo[a]pyrene purine deoxyribonucleoside-3'-phosphate adducts were postlabeled with [32P]ATP and T4 kinase and the positions of these individual bisphosphates were mapped by TLC. Though all eight adducts migrated to the same general region of the thin layer plates, the four possible adducts from each enantiomeric dihydrodiol epoxide were resolved. PMID- 1904322 TI - Sequential renal alterations in septic shock in the primate. AB - This is a descriptive sequential study of the response of the baboon to LD100 Escherichia coli. The response was found to consist of three stages based on electron microscopic, physiologic, and clinical laboratory data. This study associates the inflammatory, coagulant, and cell injury (stage 1-3) responses with markers of activation of inflammatory cells (tumor necrosis factor) and of the vascular endothelium (tissue plasminogen activator). This work also shows that in contrast to the underlying parenchymal cells of the organ, the vascular endothelium remains intact throughout the response to LD100 E. coli. The possible role of the vascular endothelium in mediation of events at both its luminal (blood) and antiluminal (parenchymal) surfaces is discussed. PMID- 1904323 TI - Effects of dopamine and dobutamine on skeletal muscle oxygenation in normoxemic rats. AB - The effects of two vasoactive drugs, dopamine and dobutamine, on skeletal muscle tissue oxygenation were studied in a normoxemic rat model. It is usually claimed that drugs may increase or decrease oxygen delivery to tissues. However, this claim is only valid on the global level. Our interest is directed towards individual organs. Two groups of rats (n = 7 each) were studied. One group received dopamine, the other dobutamine. Blood gases, hematocrits, and mean arterial blood pressures were measured in addition to tissue pO2. Infusion of dopamine 2.5 micrograms/kg/min resulted in a statistically significant decrease in skeletal muscle pO2. Higher doses of dopamine, and all doses of dobutamine, did not influence pO2 at all. The results raise the question of whether blood flow to vital organs may be negatively affected by dopamine 2.5 micrograms/kg/min. Direct measurements of tissue oxygenation are warranted in, e.g., the liver and gut. PMID- 1904324 TI - Disodium cromoglycate (DSCG) selectively inhibits IgE production and enhances IgG4 production by human B cell in vitro. AB - The effect of DSCG on human IgE production in vitro was studied. DSCG selectively inhibited interleukin-4 (IL-4) induced IgE production by mononuclear cells (MNC) from normal donors without affecting IgM, IgA, IgG1, IgG2 or IgG3 production. In contrast, DSCG enhanced IgG4 production. To achieve this effect, DSCG must be added to the culture at the initiation and be present throughout the entire culture period. Interferon-gamma (IFN-gamma) also inhibited IL-4-induced IgE production, but IgG4 production was not affected by IFN-gamma. Monoclonal anti IFN-gamma antibody blocked the inhibition of IgE production by IFN-gamma, but did not block the inhibition of IgE production by DSCG. DSCG also selectively inhibited spontaneous IgE production and enhanced IgG4 production by B cells from atopic patients in the presence of T cells and monocytes. These results indicate that there is a mechanism of IgE production inhibition which is not mediated by IFN-gamma. We also found that DSCG is an excellent reagent for the study of IgE and IgG4 regulation in vitro. PMID- 1904325 TI - Interleukin-2 inhibits the interleukin-4-induced human IgE and IgG4 secretion in vivo. AB - The effect of interleukin-2 (IL-2) on IL-4-induced IgE and IgG4 secretion by B cells in peripheral blood mononuclear cell (PBMC) preparations from non-atopic healthy humans and atopic dermatitis patients was investigated. PBMC were cultured at an optimal concentration of recombinant IL-4 with or without addition of IL-2 for 10 days. Native and recombinant IL-2 inhibited the IL-4-induced IgE and IgG4 secretion in a dose-dependent manner by cells from both normal and atopic donors. Rabbit antibodies to IL-2 or to the monoclonal anti-IL-2 receptor antibody anti-TAC reversed the IL-2 effect. Culturing cells with IL-4 and IL-2 for 1 or 2 days only slightly suppressed the IgE and IgG4 secretion whereas addition of IL-2 to IL-4 containing cultures on day 4 or 5 inhibited the IgE and IgG4 secretion more effectively. This is in contrast to interferon-gamma (IFN gamma) which inhibited the IL-4 induced IgE and IgG4 secretion when added for the first 24 or 48 h but had no effect when added on days 4 or 5. The data demonstrate that both IL-2 and IFN-gamma act as antagonists in the IL-4-induced IgE and IgG4 secretion by human B cells; while IL-2 appears to inhibit relatively late in culture, IFN-gamma has an early inhibitory effect, suggesting that the two lymphokines inhibit the IL-4 effect by different mechanisms. PMID- 1904326 TI - Effect of swainsonine on interleukin-2 alpha chain receptor expression and proliferation of human lymphocytes. AB - Swainsonine, an inhibitor of mannosidase II, involved in N-linked glycoprotein processing, modifies expression of cell surface receptors. This alkaloid has strong anti-metastatic and immunomodulatory activity; it enhances stimulation of lymphocytes triggered by concanavalin A (ConA) but suppresses stimulatory effects of phytohaemagglutinin (PHA). We presently observe that swainsonine decreases expression of the interleukin-2 (IL-2) receptor (IL-2R) on PHA-stimulated human peripheral blood lymphocytes, measured by binding of a monoclonal antibody that recognizes the 55-kD glycoprotein subunit (alpha) of this receptor. Proliferation of the PHA-stimulated lymphocytes is suppressed by swainsonine, which manifests in the decreased proportion of both cells entering G1 (from G0) and those progressing through S. G2 and M. This suppression can be overcome by addition of IL-2 into cultures. In contrast, swainsonine has no effect on IL-2R expression and stimulation (cell cycle progression) of lymphocytes triggered by the monoclonal antibody OKT3. The data suggest a possibility that the observed swainsonine effects on lymphocytes stimulated by PHA are mediated via surface receptors other than IL-2R. These receptors may appear prior to IL-2R and be also involved in cell stimulation by PHA but not by other mitogens. PMID- 1904327 TI - The role of aldose reductase inhibition in diabetic neutrophil phagocytosis and killing. AB - This study examines whether an aldose reductase inhibitor (statil, ICI) can enhance neutrophil oxidative killing by diabetic neutrophils. We have examined a radiometric assay of phagocytosis and killing of Candida albicans by neutrophils from 20 controls and 20 subjects with insulin-dependent diabetes under various in vitro glucose concentrations. Glucose was present at 5, 10 and 20 mM in the presence and absence of statil (11 microM). Phagocytosis was unaffected by raised glucose levels in controls and in diabetic subjects. Killing by the diabetic cells was inhibited by increasing concentrations of glucose, killing was 18.9 +/- 2.0, 16.9 +/- 2.4 and 14.8 +/- 2.0% (mean +/- s.e.m.) at 5, 10 and 20 mM glucose, respectively (P less than 0.05). With the addition of statil under the same conditions killing improved to 19.3 +/- 2.0, 23.2 +/- 2.2 and 23.6 +/- 2.4 (P less than 0.01), these values were similar to the controls (P greater than 0.01). We conclude therefore that aldose reductase inhibition restores oxidative killing to normal. PMID- 1904328 TI - Activation of complement during apheresis. AB - C3 activation products and the terminal complement complex (TCC) were examined in plasma during plasmapheresis of patients with Guillain-Barre Syndrome (GBS) (n = 4), Waldenstrom's syndrome (n = 4), and hypercholesterolaemia (n = 1), or during cytapheresis of platelet (n = 10) and granulocyte (n = 2) donors. Blood specimens were taken before, during and after the procedures. There was a significant activation of complement after apheresis in the GBS patients and one of the patients with Waldenstrom's syndrome, but not in the other patients. There were no significant differences in complement activation products before compared with after cytapheresis in the healthy donors. This demonstrates the biocompatibility with respect to complement activation of the materials used. The observed complement activation in some of the patients during plasma exchange is probably caused by activation products in the replacement plasma. PMID- 1904330 TI - Soluble CD4 in patients with rheumatoid arthritis and osteoarthritis. AB - An ELISA was used to measure the soluble form of the leukocyte surface antigen CD4 (sCD4) in the sera and synovial fluids (SF) of patients with rheumatic diseases. Patients with rheumatoid arthritis (RA) had raised levels of sCD4 in both their sera and synovial fluid compared to age-matched healthy controls. In patients with osteoarthritis levels of sCD4 in SF and sera were lower than in RA but higher than in sera of healthy individuals. Mononuclear cells from the synovial fluid of RA patients were found to produce spontaneously high levels of sCD4, but autologous blood cells only produced comparable levels after in vitro stimulation with mitogenic lectin. In individual RA patients with active disease, serial sCD4 levels fell preceding clinical improvement. In three patients where serum sCD4 levels fell and clinical improvement occurred, subsequent small increases in serum sCD4 preceded increased clinical disease activity by up to 5 days. Synovial fluid levels of sCD4 correlated positively with soluble interleukin 2 receptor levels but no correlation was found with sCD8 levels. We conclude that the release of sCD4 reflects the involvement of T helper cells and macrophages in the pathogenesis of joint inflammation, especially in RA. PMID- 1904329 TI - Cyclosporine A and prednisolone inhibit lectin- and alloantigen-induced release of sCD8: correlation with proliferative responses. AB - It has been shown previously that there is a strong correlation between the in vitro release of soluble CD8 glycoprotein (sCD8) and CD8+ T lymphocyte activation. In the present study, the lectin stimulation of peripheral blood mononuclear cells (PBMC) induced a dose-dependent release of sCD8 which correlated with the magnitude of CD8 lymphocyte activation as measured by the expression of the interleukin 2 (IL-2) receptor and HLA-DR antigen and of the T cell proliferative responses. Both the proliferative responses and the release of sCD8 were inhibited by cyclosporine A (CyA) and prednisolone (PRED) in a concentration-dependent manner. When the immunosuppressants were present for only 60 min before the initiation of the cultures, an inhibitory effect was also seen, but this was maximal only when the agents were added at the initiation of the culture period; when the addition of CyA or PRED was delayed for either 24 or 48 hr after the initiation of the culture, the degree of inhibition of the proliferative response was greatly reduced. However, there was a significant inhibition of sCD8 release by CyA even when it was added 48 hr after the culture initiation. The addition of recombinant IL-2 did not affect the lectin-induced sCD8 release. The inhibition of the lectin-induced proliferative response and sCD8 release by PRED, but not that by CyA, was reversed by the recombinant IL-2. Alloantigen stimulation also induced sCD8 release and this release was inhibited both by CyA and by PRED. These data, together with the known effects of CyA on differentiation, clonal amplification, and activation of CD8 T lymphocytes, suggest that in vitro sCD8 release occurs during the early stages of activation of CD8+ cytotoxic T cells. PMID- 1904331 TI - Mechanisms of depressed natural killer cell activity in recurrent aphthous ulcers. AB - Natural killer (NK) cell activity was studied serially in the peripheral blood obtained from 35 patients with recurrent aphthous ulcers (RAU) and from 46 age/sex-matched normal healthy controls. The NK cell activity was assayed by a 4 hr 51Cr release assay using K562 cells as targets. The results showed that the patients in remission (2 weeks of convalesence) had normal NK cell activity compared to that of normal controls. Four stages of evolution (early, exacerbation, postexacerbation, and convalescence) in these patients were further evaluated. Increased NK cell activity in the exacerbation of major aphthous ulcer was noted. In contrast, depressed NK cell activity in postexacerbation and in 1 week of convalescence was found at different effector/target (E/T) ratios. The depressed NK cell activity was interpreted as temporary and a secondary phenomenon in the immunopathogenesis of this disease. Partial restoration of depressed NK cell activity by adding recombinant interleukin-2 (rIL-2) suggests that other factors are also involved in the process or that IL-2 deficiency exists in RAU patients. However, no deficiency of plasma IL-2 and interferon gamma (IFN-gamma) was noted. The percentage of large granular lymphocytes (LGL, NK/K) was correlated with NK cell activity, with both parameters being depressed in the postexacerbation of RAU patients. NK cell activity of RAU patients was still depressed after the depletion of plastic adherent cells. Suprisingly, in contrast to the remission stage, unresponsiveness to rIL-2 of normal NK cell activity in the exacerbation stage was found. The discrepancy was not associated with different subpopulations of NK heterogeneous cells. Immunopathogenesis of RAU on the NK-IFN-IL-2-IL-2R system needs further clarification. PMID- 1904332 TI - Defective T lymphocyte function in nonthymectomized patients with myasthenia gravis. AB - In vitro functional properties of peripheral blood mononuclear cells were evaluated in 29 patients with myasthenia gravis and in 11 healthy controls. Spontaneous cell proliferation was higher in patients than in controls. The production of interleukin-2 and interferon-gamma and the proliferative response to different mitogens were reduced in the patients. A positive correlation was found between the production of interleukin-2 and interferon-gamma. These defects in T cell function were the most pronounced in nonthymectomized patients. Patients with severe disease had a higher percentage of cells bearing the interleukin-2 receptor and a higher spontaneous production of tumor necrosis factor alpha in cell culture than in patients with mild disease. There was no difference between patients and controls in the level of soluble interleukin-2 receptor in cell culture supernatants or in sera. The results indicate a partially suppressed T cell function in myasthenia gravis. This defect was less pronounced in patients studied after thymectomy. PMID- 1904334 TI - Laser radiation at various wavelengths for decompression of intervertebral disk. Experimental observations on human autopsy specimens. AB - The interaction of laser radiation with the nucleus pulposus from autopsy specimens of human intervertebral disks was evaluated at different wavelengths (193 nm, 488 nm & 514 nm, 1064 nm, 1318 nm, 2150 nm, 2940 nm, and 10600 nm). A significant correlation of linear least squares fit of the mass ablated as a function of incident energy was found for all lasers used except the Excimer at 193 nm. The 2940-nm Erbium:YAG laser was most efficient in terms of mass of disk ablated per joule in the limited lower range where this wavelength was observed. At higher energy levels, the CO2 laser in the pulsed mode was most efficient. However, the Nd:YAG 1064-nm and 1318-nm lasers are currently best suited for percutaneous laser disk decompression because of the availability of usable waveguides. Carbonization of tissue with the more penetrating Nd:YAG 1064-nm laser increases the efficiency of tissue ablation and makes it comparable to the Nd:YAG 1318-nm laser. PMID- 1904333 TI - Once-daily pravastatin in patients with primary hypercholesterolemia: a dose response study. AB - This multicenter, double-blind, placebo-controlled study was conducted to evaluate dose-response effects and safety of once-daily administration of pravastatin, a new inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. Pravastatin 5, 10, 20, 40 mg or placebo was administered at bedtime to 150 patients with primary hypercholesterolemia inadequately controlled on a low fat, low-cholesterol (AHA Phase I) diet. After 8 weeks of treatment, pravastatin produced dose-dependent reductions in low-density lipoprotein (LDL) cholesterol of 19.2 to 34.1% (p less than or equal to .001 vs. baseline and placebo) and reductions in total cholesterol of 14.3 to 25.1% (p less than or equal to .01 to p less than or equal to .001 vs. placebo and p less than or equal to .001 vs. baseline). The relationship between the loge dose of pravastatin and decrease in LDL cholesterol was linear (p less than 0.002). High-density-lipoprotein cholesterol increased up to 11.7% and triglycerides decreased by as much as 23.9%. Pravastatin was well tolerated; no patient withdrew from the study as a consequence of treatment-related adverse events. Despite its relatively short serum half-life of approximately 2 h, once-daily administration of pravastatin provides a safe and effective means of reducing elevated LDL and total cholesterol. PMID- 1904335 TI - Strength retention of chromic gut and synthetic absorbable sutures in a nonhealing synovial wound. AB - The rate at which absorbable sutures lose their mechanical strength in a slow healing wound is clinically important, particularly because the factors inhibiting normal healing are not always apparent at the time of closure. Sutures of chromic catgut and two monofilament absorbable synthetic suture materials (polydioxanone and polyglyconate) were used to close a synovial incision in the knees of sheep. A corticosteroid was applied around the wound resulting in minimal tissue healing when the sutures were retrieved up to six weeks later. The failure load and maximum tensile strength of the retrieved sutures were measured. The mechanical degradation of the materials followed a pattern similar to that in normally healing wounds except that the early fragmentation of chromic gut and polydioxanone occurred far less frequently and neither weakened further after three weeks. Polyglyconate was significantly the strongest material up to three weeks but thereafter continued to weaken. The strength of absorbable sutures was retained longer than in a healing lesion probably because of the absence of the phagocytic cells of an inflammatory tissue. PMID- 1904336 TI - The use of aspirin to prevent heterotopic ossification after total hip arthroplasty. A preliminary report. AB - The reported incidence of heterotopic ossification (HO) after total hip arthroplasty (THA) ranges up to 50%. HO causes pain and restricted range of motion (ROM) in a significant number of these THA patients. From 1983 to 1988, 177 primary cemented THAs were performed in 131 consecutive patients. Six hundred fifty milligrams of buffered aspirin administered twice daily for two weeks was used as a prophylaxis for thromboembolic disease. There was an unusually low incidence of HO in this group of patients. Aspirin treatment was instituted the night before surgery and continued for two weeks, except in 13 patients (7%) who had to stop treatment because of gastrointestinal symptoms. All patients had at least one year of roentgenographic study postoperatively. According to the Brooker Classification of HO, there were 169 (96%) Grade I and Grade 0 hips, six (3%) Grade II, two (1%) Grade III, and no Grade IV. None of the patients had symptomatic restriction of ROM attributable to heterotopic bone. Aspirin is a safe and inexpensive agent for prevention of HO after THA. PMID- 1904337 TI - [A case of amyotrophic lateral sclerosis with disturbance of vertical ocular movement responding to thyrotropin releasing hormone (TRH)]. AB - A 64-year-old woman who had amyotrophic lateral sclerosis (ALS) with disturbance of vertical ocular movement was presented. She was admitted to our hospital with progressive dysphagia, dysarythria and weakness of the extremities. Neurological examinations revealed disturbance of vertical ocular movement with normal doll's eye phenomenon (supranuclear origin), bulbar palsy, muscle weakness of the extremities, extensor plantar signs, and fasciculations of the costal and interosseal muscles. EMG studies showed denervation potentials, and muscle biopsy demonstrated group atrophy, fiber type grouping and small angular fibers. TRH injections resulted in improvement of disturbance of vertical ocular movement, but no effect was seen on the weakness of the limb. There was about 20 Japanese cases with disturbance of ocular movement in ALS, but it was rare to see ocular movement disorder from the early stage of ALS. The pathophysiology of ocular movement disorder in ALS has been thought to be due to supranuclear origin, i.e., the disturbance in the pathway from the frontal cortex to the mesencephalon. In this case, TRH might effect at some point of the frontomesencephalic pathway. PMID- 1904338 TI - Evaluation of cerebral perfusion reserve using 5% CO2 and SPECT neuroperfusion imaging. AB - Anatomic features of carotid artery stenosis, as defined angiographically, do not necessarily correlate with the hemodynamic significance of the narrowing. The concept of regional cerebral vasodilatory (or perfusion) reserve has been advocated as a means of defining the hemodynamic compromise associated with carotid lesions. We evaluated the feasibility of using SPECT imaging with 5% CO2 using I-123 IMP (N-isopropyl iodoamphetamine) or Tc-99m HMPAO (hexamethylpropylene amineoxime) to measure cerebral perfusion reserve. Imaging was performed on six asymptomatic subjects and one patient with a history of transient ischemic attacks but no evidence of carotid artery disease. A perfusion reserve index (PRI) was defined to represent the percent increase in blood flow during 5% CO2 breathing in regions supplied by the middle cerebral artery normalized for injected dose and changes in blood pressure. Significant increases in cerebral perfusion were seen in six of the seven subjects studied while breathing the 5% CO2 (P less than 0.01). The mean of the PRI values for the seven subjects was 32%, with a range of -5% to 58%. We conclude that SPECT imaging with IMP or HMPAO can be used to quantitatively measure the cerebral perfusion response to 5% CO2. PMID- 1904339 TI - Mitomycin C contact dermatitis. PMID- 1904341 TI - Endothelin-1 stimulates the release of arachidonic acid and prostaglandins in rabbit iris sphincter smooth muscle: activation of phospholipase A2. AB - We have investigated the effects of endothelin-1 (ET1) on phospholipid hydrolysis and 3H-arachidonic acid (AA) release and prostaglandin synthesis in the rabbit iris sphincter smooth muscle. ET1 actions are concentration- and time dependent with an EC50 for AA release of 1 nM and t1/2 value of 1.5 min. We have identified the AA metabolites released by ET1, employing HPLC, as both cyclooxygenase and lipoxygenase products. The AA released by ET1 appears to derive mainly from the phosphoinositides through phospholipase A2, rather than phospholipase C activation. A key role for phospholipase A2 in AA release in the sphincter muscle is supported by the following observations. (1) Pretreatment of the labeled sphincter with the phorbol ester, PDBu (100 nM) inhibited ET1-stimulated IP3 formation, but it potentiated ET1-stimulated AA release. (2) Pretreatment of the labeled tissue with isoproterenol (5 M) inhibited ET1-stimulated IP3 production without altering AA release. (3) The potency for ET1-stimulated AA release (EC50 = 1 nM) was much higher than that for IP3 formation (EC50 = 45 nM). (4) There were considerable increases, rather than decreases, in 1, 2-diacyl-glycerol formation (1.2-folds) and its phosphorylated product, phosphatidic acid (2.6 folds) by ET1. It is concluded that in the rabbit iris sphincter ET1 is a potent agonist for AA release and eicosanoid synthesis and that AA is released from phosphoinositides mainly through activation of phospholipase A2. PMID- 1904340 TI - Glycosaminoglycan degradation by cultured retinal pigment epithelium from patients with retinitis pigmentosa. AB - Patients with certain systemic deficiencies in the degradation of glycosaminoglycans (GAGs) often suffer from a retinal degeneration similar to that seen in retinitis pigmentosa. This applies to mucopolysaccharidosis (MPS) types I, II, and III, but not to type VI. The retinal pigment epithelium (RPE) is thought to contribute significantly to the synthesis and degradation of proteoglycans in the interphotoreceptor matrix. This raises the possibility that a defect in the synthesis or degradation of GAGs by the RPE may be related to some forms of retinal degeneration. In the present work, RPE from normal and RP donors was investigated for the capacity to correct deficiencies in GAG degradation by cultured skin fibroblasts from patients with different forms of MPS. A cross-correction technique was used in which abnormal increases in the incorporation of 35S-sulfate into GAGs by MPS fibroblasts was measured in the absence or presence of RPE cultures. RPE from normal donors corrected the defects in GAG degradation of fibroblasts from patients with MPS I, II, and III, but not MPS VI. The RPE from four donors with retinitis pigmentosa (one autosomal dominant, one sex-linked, and two isolated cases) and one donor with an unclassified isolated retinal degeneration demonstrated the same capacities to correct the MPS deficiencies as did normal RPE. Therefore, although retinitis pigmentosa is a heterogeneous disorder with several possible etiologies, no evidence was found in these five patients for a defect in GAG degradation that resembles the deficiencies of MPS patients. PMID- 1904342 TI - Epileptiform EEG activity of the centromedian thalamic nuclei in children with intractable generalized seizures of the Lennox-Gastaut syndrome. AB - Centromedian thalamic nuclei (CM) epileptiform EEG activities were recorded in children with intractable generalized seizures of Lennox-Gastaut syndrome (LGS) through implanted recording-stimulating electrodes used for seizure control. Ictal CM epileptiform activities were consistently correlated to widespread surface cortical EEG activities and symptoms in all patients and all types of generalized seizures; i.e., fast spike discharges at CM correlated at onset of tonic and tonic-clonic generalized seizures; slow (1-2 Hz) spike-wave complex discharges at CM correlated for atypical absence seizures; slow polyspike-wave complex discharges correlated for myoclonic seizures; and spike bursts and suppression patterns correlated for combined tonic-atonic-myoclonic seizures. Ictal EEG activities occurred simultaneously at right and left CM and surface at onset of all seizure types, with the exception of myoclonic seizures where CM complete discharges and individual spike-wave complexes significantly lead those of the surface. Brief tonic-atonic spasms clinically undistinguishable from "real" epileptic seizures showed no EEG counterparts at CM and surface. Interictal CM spike-wave complete discharges and individual spike-wave complexes showed variable amplitude-temporal patterns. Amplitude emphasis on CM and frontopolar regions was observed in most of complete discharges, however, and phase shifts between CM and frontopolar regions were observed in individual spike wave complexes. PMID- 1904343 TI - Status epilepticus in benign rolandic epilepsy manifesting as anterior operculum syndrome. AB - We report the fourth case of partial status epilepticus (SE) in benign epilepsy of childhood with rolandic spikes (BECRS). The child suffered long-lasting attacks involving the mouth and pharynx, clinically manifest as speech arrest, sialorrhea, and drooling. Both clinical and electroencephalogram (EEG) data were compatible with the diagnosis of BECRS. Only during SE was the clinical picture similar to that observed in the operculum or Foix-Chavany-Marie syndrome. SE remission was obtained with the usual antiepileptic drug therapy (diazepam, clobazam, valproate). EEG records showed additional patterns of continuous spike waves during slow sleep and specific inhibition and blocking of interictal centrotemporal spikes by mouth and/or tongue voluntary movements. PMID- 1904344 TI - Sleep modulation of interictal spike configuration in untreated children with partial seizures. AB - Spontaneous changes in interictal spike morphology were evaluated before initiation of antiepileptic drug (AED) therapy in 38 children with uncontrolled partial seizures. Nonrapid eye movement (NREM) sleep during the first third of the night was associated with spikes of higher amplitude, longer duration, and lower degree of sharpness than those observed in wakefulness or REM sleep. Spike amplitude decreased in subsequent NREM epochs, but duration and sharpness remained relatively consistent. A NREM/REM modulatory pattern was identified, with REM periods exhibiting spikes of decreased amplitude, shorter duration, and increased sharpness as compared with NREM periods in each third of the night. The spike changes associated with REM sleep are similar to the alterations previously described as occurring coincidentally with attainment of seizure control and thus may reflect inherent modulation of epileptogenicity in synchrony with sleep cycles. PMID- 1904345 TI - Magnetic resonance imaging and late-onset epilepsy. AB - The value of magnetic resonance imaging (MRI) in investigation of patients with late-onset epilepsy has not been studied systematically. We evaluated prospectively the usefulness of MRI in 50 patients with late-onset epilepsy in whom a computed tomography (CT) scan was normal (32), did not allow a definitive diagnosis to be made (12), or showed irrelevant lesions (6). Patients were assessed clinically and had an EEG, and CT and MRI scans were reported by one neuroradiologist blinded to clinical and laboratory data. Of the 32 patients with a normal CT scan, MRI was normal in 20, showed irrelevant ischemic lesions in 8, and showed the cause of seizures in 4 patients. Of the 12 patients with nondiagnostic CT, MRI clarified the diagnosis in 5 and was normal in 2 patients. In 6 patients, both scans showed irrelevant ischemic lesions, and in 1 patient MRI showed a relevant additional lesion. The incidence of MRI-detected white matter ischemic lesions was no greater than in an age- and sex-matched group of subjects without seizures. MRI was diagnostic in 32% of the patients with partial seizures and/or focal EEG findings, as compared with 0% of patients without focal features (p less than 0.01). We conclude that MRI is useful in investigation of patients with late-onset epilepsy with focal features. PMID- 1904347 TI - Antithrombotic actions of aspirin in the horse. AB - The antithrombotic effects of aspirin at two dose rates (4 mg/kg and 11 mg/kg bodyweight [bwt] were evaluated in normal, healthy ponies by measuring template bleeding time. Inhibition of platelet aggregation in response to adenosine diphosphate (ADP) and collagen was evaluated and cyclo-oxygenase activity was monitored by radioimmunoassay of thromboxane B2 (TXB2), the stable metabolite of thromboxane A2 (TXA2). TXB2 was measured in serum and platelet rich plasma. Bleeding time was prolonged significantly until 48 h after treatment at 12 mg/kg bwt and until 4 h at the lower dose rate. Synthesis of TXB2 and collagen induced aggregation were diminished for much greater periods with similar results at each of the dose rates. The prolonged effects of aspirin on platelet function occurred in spite of a very short plasma half-life of aspirin, because of its irreversible action on platelet cyclo-oxygenase. The results show that low dose aspirin has a potential role in antithrombotic therapy in horses although the relationship between skin bleeding time in normal horses and improvement of clinical conditions requires further research and evaluation in clinical trials. TXB2 measurement appears to overestimate the duration of antithrombotic effects of aspirin in vivo. PMID- 1904346 TI - Discontinuation of phenytoin and carbamazepine in patients receiving felbamate. AB - Five patients participated in a controlled discontinuation of phenytoin (PHT) and carbamazepine (CBZ) after a study in which all subjects had felbamate (FBM) added to both PHT and CBZ. Four subjects (three women and 1 man aged 23-36 years) completed the protocol. Mean total seizure frequency per day with PHT and CBZ was 1.33 +/- 0.93 (mean +/- SEM), decreasing to 0.87 +/- 0.71 with addition of FBM, and 0.82 +/- 0.78 after discontinuation of PHT. Only one subject tolerated discontinuation of CBZ; the other three had dosage reductions of 33, 54, and 63%. Toxicity attributable to FBM was not observed, and patients often described less severe seizures. Results from four refractory patients indicated that FBM was able to replace PHT and reduce the need for CBZ. In addition, as PHT dosages were reduced, FBM clearance decreased 21%. As the CBZ dosages were reduced. FBM clearance decreased an additional 16.5%. PMID- 1904348 TI - Muscle disorders in the horse: a retrospective study. AB - Case records of horses with muscle disorders presenting to the Veterinary Medical Teaching Hospital of the University of California, Davis, over a nine year period were evaluated. The objectives of the review were to identify the common myogenic muscle problems and their clinical features. Muscle disease of idiopathic aetiology following exercise was by far the most common condition noted. Other causes of myogenic muscle disorders included congenital, infectious, immune mediated and nutritional factors. PMID- 1904349 TI - On 'jumbo' and 'junkie' trials. A fumbled affair, a jungle, or the ultimate solution? PMID- 1904350 TI - Tissue plasminogen activator and other risk factors as predictors of cardiovascular events in patients with severe angina pectoris. AB - The value of measurements of the fibrinolytic factors, tissue plasminogen activator and plasminogen activator inhibitor, for predicting death and non-fatal cardiovascular events was studied in 213 consecutive patients with angiographically documented coronary artery disease. In the course of 4-year follow-up, 47 patients (22.1%) had at least one cardiovascular event. We found the incidence of cardiovascular events to be positively associated with high tissue plasminogen activator antigen concentration, in addition to previous myocardial infarction, low ejection fraction, hypertension, high body mass index and high triglyceride levels. Cholesterol was not found to be associated with cardiovascular events. A high concentration of tissue plasminogen activator antigen thus implies an increased risk of cardiovascular events in patients with severe angina pectoris. PMID- 1904351 TI - Prolonged myocardial stunning after thrombolysis: can left ventricular function be assessed definitely at hospital discharge? AB - To assess whether myocardial dysfunction after acute reperfusion ('stunning') may show delayed recovery, 33 patients of the European Cooperative Study (rtPA vs placebo) had radionuclide angiocardiography on day 9 and after 3-6 months. Sixteen patients (13 inferior, three anterior infarcts) had a normal left ventricular ejection fraction (LVEF) which remained unchanged (55.4 vs 53.9%). In contrast, LVEF of 17 patients (10 inferior, seven anterior infarcts) with depressed values on day 9 improved during follow-up from 38.8 to 45.2% (P less than 0.01). Improvement was only observed in patients with early reperfusion defined a priori as peak creatine kinase value less than or equal to 15 h of pain onset (from 40.9 to 49.3%; P less than 0.05) in contrast to patients without reperfusion (from 34.0 to 35.2%; ns). Accordingly, LVEF increased in patients with open infarct-related arteries at hospital discharge (n = 8; P = 0.053) but not with persistent occlusion (n = 7; P = 0.11). Thus, a depressed LVEF observed 9 days after reperfusion may show delayed recovery due to prolonged stunning. Therefore, after thrombolysis, left ventricular function may not be evaluated definitively at hospital discharge; results of such studies should be interpreted with caution. PMID- 1904352 TI - Comparison of costs of percutaneous transluminal coronary angioplasty (PTCA) and coronary artery bypass graft surgery (CABG) for patients with angina pectoris. PMID- 1904353 TI - The changes of interleukin-2, tumour necrotic factor and gamma-interferon production among patients with Kawasaki disease. AB - Included in this study were 43 cases of mucocutaneous lymph node syndrome (MCLS or Kawasaki disease) treated solely with aspirin. Of these, 19 developed coronary aneurysm. Mononuclear cells (MNC) of these MCLS patients were collected weekly and stimulated either with phytohaemagglutinin (PHA) or PHA plus phorbol myristic acetate. The production of interleukin-2 (IL-2), tumour necrotic factor (TNF) and gamma-interferon (IFN-r) was determined. In addition, IL-2, TNF, IFN-r from serial collections of serum samples of these patients were also measured. The results show that serum IL-2 and TNF were detected in the 1st week, reached maximal plateau in the 2nd and 3rd week and decreased 1 month later. The production of IL-2, TNF and IFN-r from MCLS patients' MNC increased from the 1st to the 3rd week, persisted at a high level for 1 month and then decreased. During the 2nd and 3rd weeks, there were significantly higher serum IL-2 levels and IL-2 production in patients with than in patients without coronary lesions. These observations suggest that the serum IL-2 level and IL-2 production during the 2nd week may serve as a predictive parameter for coronary aneurysm formation. It also suggests that the production of TNF, IL-2 and IFN-r from MNC may contribute to the development of vascular injury in acute MCLS. PMID- 1904354 TI - Effects of a MAO-B inhibitor in the treatment of Alzheimer disease. AB - 119 patients were enrolled in a double-blind randomized parallel study versus placebo carried out to assess both the efficacy and tolerability of L-deprenyl (10 mg/day) for treatment of patients with organic mental disorders of the Alzheimer type (DAT). The treatments were given for 3 months, starting after a run-in period of 15 days to evaluate efficacy. A complete neuropsychological battery was administered monthly after the start of treatment whereas tolerability was assessed by checking, recording and classifying all the unfavorable experiences occurring. According to the results, L-deprenyl would seem to be a useful and reliable tool for the treatment of DAT patients in an attempt to improve their cognitive functions and reduce behavioral alterations, without frequent or severe side effects. PMID- 1904355 TI - Clinical pharmacology of pravastatin, a selective inhibitor of HMG-CoA reductase. AB - Pravastatin, lovastatin and simvastatin are HMG-CoA reductase inhibitors with very similar structures. However, minor substitutions in the decalin ring have resulted in major differences in physiocochemical, pharmacological, and pharmacokinetic properties. Both in vitro and in vivo studies have demonstrated that lovastatin and simvastatin are non-selective lipophilic inhibitors, while pravastatin is a selective hydrophilic inhibitor. An extensive clinical pharmacology program has been conducted for pravastatin. Radiolabelled studies demonstrated oral absorption and bioavailability values of 34% and 17%, respectively. The parent drug is cleared equally by renal and non-renal routes. Peak blood level after oral administration is reached at approximately 1 h and the mean plasma elimination half-life is 1.8 h. Binding of total radioactivity to plasma proteins averages 45%. Non-radiolabelled studies showed that mean areas under the plasma concentration-time curves (AUC) and maximum plasma concentrations (Cmax) are proportional to the doses administered, whereas times to reach Cmax (Tmax) and plasma elimination half-life values are independent of dose. Measurement of trough plasma concentrations of pravastatin at steady state showed no evidence of drug accumulation. Pharmacodynamic studies demonstrated an average LDL-C decrease of 30-35% at a daily dose of 40 mg. HDL-C increases are between 10% and 25% and triglyceride decreases, between 10% and 25%. These results indicate that pravastatin is very effective in lowering LDL-C. With its consistent decrease in triglycerides and increase in HDL-C, pravastatin offers a well-balanced lipid-modulating response. PMID- 1904356 TI - Inhibition of cholesterol absorption by HMG-CoA reductase inhibitor. AB - In subjects with familial hypercholesterolemia cholesterol absorption efficiency was insignificantly reduced during a short-term more consistently during long term pravastatin treatment. A cholesterol feeding had no effect on LDL cholesterol level but reduced absorption efficiency during a long-term lovastatin treatment. PMID- 1904357 TI - Comparison of different HMG-CoA reductase inhibitors. AB - The HMG-CoA reductase inhibitors have been shown to cause marked reduction of cholesterol and offer a new and effective approach to treatment of hyperlipoproteinemia. Three agents, pravastatin (P), lovastatin (L) and simvastatin (S), have been studied with reference to long-term lipid-lowering effect, tolerance and clinical safety. Following a dietary lead-in period of at least 6 weeks in every case, patients with primary hypercholesterolemia were enrolled from participants of short-term controlled studies which after completion were extended as open studies. Treatment was administered over 6 months with 20 mg S (84 patients), L (42 patients) or P (23 patients) twice daily. Total cholesterol was decreased with S by 30.2% of basal, with L by 25.5%, and with P by 28.2%. The decrease in apolipoprotein B was 28.4%, of basal, with S 16.4% and in P 19.2%. Triglycerides were lowered by 19.6% of basal with S by 17.4%, with L, and by 6.4% with HDL-cholesterol increased in the S group by 23% of basal, by 9.7% in the L group, and by 8.0% in the P group. No serious clinical or laboratory abnormalities were observed. In the S group headache (3.6% of patients), abdominal discomfort (2.4%), sleeping disturbances (3.6%), and muscle pain (2.4%) were reported. In the L group headache (7.1%), abdominal discomfort (4.8%), sleep disorders (4.8%), and muscle pain (4.8%) were observed. In the P group one patient complained of abdominal discomfort (8.7%) and one of sleep disorders (8.7%). Increases in CPK were observed in the S group (4.8% of patients) and in the L group (11.9%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1904358 TI - Cell surface expression of the short immunoglobulin mu chain (D mu protein) in murine pre-B cells is differently regulated from that of the intact mu chain. AB - Pre-B cells carrying DJH rearrangements in an appropriate reading frame produce a short mu protein consisting of a DJH and the C mu & sequence (D mu protein). We analyzed a D mu-producing Abelson-murine leukemia virus-transformed murine pre-B line, 300-19, and demonstrated that D mu proteins are expressed on the cell surface in association with surrogate L chain proteins (lambda 5 and VpreB). However, when we introduced an expression vector coding for the D mu protein into the null pre-B line P17-27, which produce lambda 5 and VpreB but no Ig molecules, most of the cells did not express D mu proteins on the cell surface although D mu proteins were produced intracellularly. On the other hand, P17-27 brings intact mu chains on the cell surface, when a vector coding for the intact mu chain is introduced. Thus, cell surface expression of the D mu protein has different requirements from that of the intact mu chain. A possible role of the VH protein encoded by germ-line VH transcripts is discussed. PMID- 1904359 TI - Immunotherapeutic elimination of syngeneic tumors in vivo by cytotoxic T lymphocytes generated in vitro from lymphocytes from the draining lymph nodes of tumor-bearing mice. AB - The draining lymph nodes (LN) of mice injected with viable syngeneic tumor cells contain populations of lymphoid cells which are capable of generating functional cytotoxic T lymphocytes (CTL) during an in vitro culture period without the need of secondary stimulation with irradiated tumor cells or addition of exogenous cytokines. Intravenous injection of as few as 2.5 x 10(6) tumor-reactive effector cells generated using this protocol effectively eliminated challenges of tumor cells at distal skin sites, whereas injection of cultured control lymphoid cells was ineffective at rejecting tumor challenges. The anti-tumor CTL generated from the draining LN of C57BL10 mice immunized with viable syngeneic tumor cells were found to be specific for the tumor used for immunization both in vitro and in vivo. Phenotypic analysis of the cells responsible for tumor elimination (both in vitro. and in vivo) demonstrated the anti-tumor effector cells to be CD4-CD8+ asialo GM1+NK1.1-. Finally, anti-tumor CTL generated during the short in vitro culture period were able to effectively reject pre-existing tumors in vivo in a systemic fashion. These data indicate that the generation of tumor-reactive CTL from the lymphoid cells contained in the LN draining the site of a tumor may provide a valuable source of effector cells which can be used in the immunotherapeutic treatment of cancer. PMID- 1904360 TI - Class II-restricted IgG2ab-specific T cells recognize a signal-minus form of the V-CH3b antigen. AB - To study the question when and where self peptides become associated with major histocompatibility complex class II molecules for tolerance induction, we recently developed a system in which the intracellular site(s) of antigen expression could be manipulated using gene cloning techniques. We previously constructed a truncated IgGa gene comprising a variable (V) domain and the CH3 domain (not including the membrane exons) from the IgG2ab heavy (H) chain. The secreted form of the V-CH3b protein was expressed at high levels under control of the Ig H chain enhancer in Ia+ B lymphoma cells and was efficiently recognized by class II-restricted IgG2ab-specific T cell hybrids. Here we describe a modified V CH3b gene construct in which the sequences encoding the signal peptide were deleted. A strong argument can be made that the signal-less V-CH3b protein is predominantly expressed in the cytosol. We show that transfected L cell lines expressing the signal-less form of the V-CH3b protein can stimulate class II restricted IgG2ab-specific T cells. Cell mixing experiments indicate that this response cannot be due to passive uptake of soluble antigenic peptides released into culture supernatants. These experiments demonstrate that a cytoplasmic protein having no obvious means of reaching the cell surface can be presented to class II-restricted T cells. PMID- 1904361 TI - The mouse IgH 3'-enhancer. AB - A lymphoid-specific transcription enhancer element has recently been identified at the far 3' end of the rat immunoglobulin heavy chain (IgH) locus. Sequence analysis presented here reveals that this enhancer is flanked by a 350-bp invert repeat, giving a structure reminiscent of a transposable element. We therefore screened for the equivalent enhancer in the mouse to determine whether its presence was conserved during evolution. A mouse homologue was indeed identified and is located 16 kb downstream of the C alpha 1 exon. It is also flanked by invert repeats and these are not repeated throughout the genome. The mouse and rat enhancers retain high sequence homology. As regard activity, the IgH 3' enhancer is lymphoid specific. However, this activity was detected in two plasmacytoma lines tested but not in two B cell lymphomas nor in HeLa cells suggesting that the enhancer may only play a stage-specific role during lymphocyte differentiation. As regards function within the IgH locus, we found that inclusion of the mouse IgH 3'-enhancer (in addition to the intron-enhancer) on mu gene expression plasmids effected a small increase in mu mRNA levels in stable plasmacytoma transfectants. PMID- 1904362 TI - V lambda and J lambda-C lambda gene segments of the human immunoglobulin lambda light chain locus are separated by 14 kb and rearrange by a deletion mechanism. AB - We have cloned a region of 124 kb of the human immunoglobulin lambda light chain locus on chromosome 22 encompassing seven V lambda and seven J-C lambda gene segments. No further C lambda gene segment was found in a region of 35 kb downstream of C lambda 7, which encodes the Ke+Oz- isotype. The C lambda proximal V lambda gene segment V lambda III. 1 is located 14.5 kb upstream of C lambda 1. The five sequenced V lambda genes have the same transcriptional orientation as the J-C lambda gene segments which is likely to be true for the majority of the V lambda gene segments in the human lambda locus and which suggests a deletion mechanism for DNA rearrangement. This is supported by hybridization of V lambda gene probes to germ-line and rearranged DNA from lambda light chain-producing cell lines. Sequences of 23 cDNA clones allow to establish a V lambda subgroup classification based on nucleic acid sequence data and an estimate of the J-C lambda usage. PMID- 1904363 TI - Vaccination of class I major histocompatibility complex (MHC)-restricted murine CD8+ cytotoxic T lymphocytes towards soluble antigens: immunostimulating ovalbumin complexes enter the class I MHC-restricted antigen pathway and allow sensitization against the immunodominant peptide. AB - In vivo induction of anti-ovalbumin (OVA) cytotoxic T cell responses was brought about in an MHC class I-restricted fashion by immunizing H-2b mice with OVA in immunostimulating complexes (ISCOM). ISCOM formation with the hydrophilic soluble protein OVA was achieved upon unmasking hydrophobic protein domains by treatment at low pH values. The effector cells induced were MHC restricted, specific for the immunodominant peptide of OVA (258-276), and expressed the CD8+ CD4- phenotype. These results suggest that ISCOM-based vaccines may be useful to direct hydrophilic soluble antigens into the MHC class I presentation pathway in order to vaccinate CD8+ T lymphocytes. PMID- 1904365 TI - Evaluation of the avidity of IgG anti-mycobacterial antibodies in tuberculous patients serum by an A-60 immunoassay. AB - A serological test for the detection of circulating IgG antibodies against the mycobacterial antigen A60 was used to analyse the avidity of antibodies raised in the serum of tuberculous patients. The avidity of the detected antibodies appeared variable and was quite low in some of them. The effect that this phenomenon has on the determination of antibodies with this test are discussed. PMID- 1904364 TI - Effects of estradiol on the prolactin surges and the feedback mechanisms of gonadotropins in pseudopregnant rats. AB - The influences of estradiol on the prolactin (PRL) surges and on the secretion of gonadotropins (LH and FSH) were investigated in the pseudopregnancy (PSP) of acutely ovariectomized rats. The four following experimental groups were prepared: 1) intact PSP as a control, 2) ovariectomy was performed on day 0 of PSP (OVX), 3) a Silastic tube containing estradiol was implanted for day 1-4 into the OVX rats (OVX-E 1-4), and 4) the Silastic tube was implanted for day 5-8 by the same manner into the OVX rats (OVX-E 5-8). In the OVX group nocturnal (N) PRL surges were observed at 0500 h on days 4, 8 and 12 examined, and increased secretions of LH and FSH were noted. In the OVX-E 1-4 group, the N PRL surge was suppressed on day 4, and the suppressed N PRL surge did not occur on day 8, after the removal of the implanted tubes. Diurnal (D) PRL surges with LH surges were observed at 1700 h on day 4 in these rats. Similarly, more remarkable results were obtained on days 8 and 12 in the OVX-E 5-8 group than in the OVX-E 1 4.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1904366 TI - Home controls of a sample of 2,414 oxygen concentrators. Sous-Commission Technique ANTADIR. AB - In France, 12,000 patients receive long-term oxygen therapy at home supplied by oxygen concentrators (OCs) which are provided by a non-profit organization, the National Home Treatment for Respiratory Insufficiency Association (ANTADIR--31 regional associations). OCs are regularly checked at home by technicians from the associations. Technical data, oxygen fraction (Fo2) supplied at working flow-rate and working duration, were recorded by technicians only during the planned home controls. Data were collected from January 15th to February 15th, 1988. Twenty three associations taking care of more than 10,000 OCs participated in the study. 2,414 machines of six different brands were controlled in the study. 77.5% of OCs had a working duration of less than 15,000 h (about 3 yrs). Working flow-rate of OCs was equal to or lower than 2 l.min-1 in 79.2% of cases. Mean Fo2 of the 2,414 measurements was equal to 92 +/- 6%. Three quarters of OCs had an Fo2 equal to or higher than the Fo2 predicted by the manufacturers. Less than 0.3% of machines were out of order (Fo2 less than or equal to 50%). We observed a significant progressive decrease in measured Fo2 in relation to flow-rate and working duration (analysis of variance (ANOVA) 2: p less than 0.001): the higher the flow rate and the longer the working duration, the lower the Fo2. We conclude that supply of used OCs has to be avoided when the prescribed flow-rate is high, and that systematic technical checks are essential to keep OCs in good working order. PMID- 1904367 TI - Pericardial diverticulum with unusual symptomatology. AB - A healthy 37 yr old female presented with recurrent right-sided chest pain which spontaneously disappeared. On a chest roentgenogram a lesion in the right cardiophrenic angle was found. Magnetic resonance imaging suggested a cystic structure. During thoracotomy a pericardial diverticulum was found. The pain was probably caused by intermittent volvulus of the diverticulum. PMID- 1904368 TI - Characteristics of the bronchial obstructive response induced by inhalation of endotoxins. PMID- 1904369 TI - The localization of the cAMP-dependent protein kinase phosphorylation site in the platelet rat protein, rap 1B. AB - Rap 1B is a low molecular weight G protein which is phosphorylated by cAMP dependent protein kinase. In order to identify the site of phosphorylation by cAMP-dependent protein kinase, purified rap 1B from human platelets was phosphorylated and subjected to limited proteolysis with trypsin. Single digestion fragment containing the phosphorylation site was obtained and purified by reversed-phase HPLC. Sequence analysis of the phosphorylated digestion fragment demonstrated that the sequence of the phosphorylation site was -Lys-Lys Ser-Ser-. This sequence is near the carboxy terminus and is adjacent to the site of membrane attachment of the protein. PMID- 1904370 TI - Cloning of the protein D2 gene of Pseudomonas aeruginosa and its functional expression in the imipenem-resistant host. AB - Protein D2 forms the water-filled pore across the outer membrane of Pseudomonas aeruginosa and allows the penetration of imipenem. We cloned the protein D2 gene by the antibody screening technique. When the imipenem-resistant mutant lacking protein D2 harbored the plasmid with the cloned D2 gene, the mutant overproduced protein D2 in the outer membrane. These transformants exhibited fully-restored imipenem susceptibility. The results prove unequivocally that protein D2 forms the imipenem-permeable pore in the P. aeruginosa outer membrane. PMID- 1904371 TI - Isolation of a novel arachidonic acid metabolite 3-hydroxy-5,8,11,14 eicosatetraenoic acid (3-HETE) from the yeast Dipodascopsis uninucleata UOFs Y128. AB - When arachidonic acid (AA) is added to the yeast Dipodascopsis uninucleata UOFS Y128, one of the major metabolites isolated and purified with the help of thin layer chromatography (TLC) and high performance liquid chromatography (HPLC) is 3 hydroxy-5,8,11,14-eicosatetraenoic acid (3-HETE). The structure of this new AA metabolite was elucidated mainly by electron impact (EI) mass spectrometry (MS). Strikingly, the formation of this new metabolite was found to be inhibited by aspirin. PMID- 1904372 TI - Cellular mono(ADP-ribosyl) transferase inhibits protein synthesis. AB - A reticulocyte translation system was depleted of functional EF-2 by treatment with diphtheria toxin (DT) fragment A and NAD. After dialysis to remove NAD, the system was reconstituted using preparations of EF-2 derived from pyBHK cells. Untreated and reconstituted lysates permitted similar rates of translation. As expected, when DT-treated EF-2 was used to reconstitute the system, no translation occurred. Furthermore EF-2, reacting with the endogenous ADP-ribosyl transferase from pyBHK cells, was also unable to restore protein synthesis in the reconstituted system. These studies suggest that eukaryotic cellular ADP-ribosyl transferases may play a role in regulating protein synthesis. PMID- 1904373 TI - Reduced thyroid-stimulating hormone response to thyrotropin-releasing hormone in autistic boys. AB - The thyroid-stimulating hormone (TSH) and prolactin responses to thyrotropin releasing hormone (TRH) were compared among four groups of boys--41 autistic, 12 mentally retarded (MR), 12 with minimal brain dysfunction (MBD) and five controls. The autistic boys were divided into two groups: DQ(IQ) greater than or equal to 80 and DQ(IQ) less than 80. Mean TSH basal and peak levels were significantly lower in both autistic groups than in the MR, MBD and control groups. Mean TSH peak value minus basal value (p-b) was significantly lower in both autistic groups than in the control group. Mean prolactin levels and p-b value did not differ among groups. It is suggested that there may be enhanced dopaminergic and/or reduced serotonergic activity in the central nervous system of autistic children, together with hypothalamic dysfunction. PMID- 1904374 TI - Behavioural disturbances in children treated with clonazepam. PMID- 1904375 TI - Stage and tissue-specific expression of fosB during mouse development. AB - The product of the fos-related fosB gene shares many properties with c-Fos such as inducibility by growth factors, complex formation with members of the Jun family and cooperative binding with Jun to the TPA response element (TRE). To investigate whether in contrast to these functional similarities, the two genes might be differentially regulated, we have analysed the expression of fosB during mouse development by in situ hybridization. A spatially restricted accumulation of fosB mRNA in the visceral yolk sac and the nervous system was observed during late gestation. The highest levels of fosB mRNA were found in the cortex and the dorsal columns of the spinal cord. Moreover, stage-specific expression was seen in sensory organs such as retina and vibrissae, where the levels of fosB RNA either increased (retina) or decreased (vibrissae) between days 15 and 18. Our results suggest that fosB may have a specific function in the development of ectoderm-derived tissues. Expression of fosB during prenatal development differs markedly from the known expression pattern of c-fos, pointing to different tissue specific functions for c-fos and fosB. PMID- 1904376 TI - Severity of illness and diagnoses in a Swedish general practice population. AB - All general practitioners at three Swedish health centres continuously assessed their patients' degree of functional deficiency on a 1-5 scale over a period of 5 1/2 years. They also registered diagnoses and certain other medical measures. Around 85% were judged to be ill to some degree, but few were seriously ill. There were small differences in functional capacity between men and women of different ages: both benign, self-limiting complaints and severe illnesses could be associated with considerable problems, while many patients with severe diseases had little discomfort. There was also a considerable discrepancy between functional impairment and work capacity. Using a combination of functional assessment with routine registration of diagnoses seems to be a useful method of obtaining a modulated, distinct picture of the types of patient encountering the general practitioner. However, further development work within the field is needed. PMID- 1904378 TI - Cost-effectiveness of extracorporeal shock-wave lithotripsy versus cholecystectomy for symptomatic gallstones. AB - To evaluate the cost-effectiveness of extracorporeal shock-wave lithotripsy vs. cholecystectomy for symptomatic gallstones, a model was constructed that projects charges and survival for both treatments. For a 45-year-old woman with one small stone, treatment with extracorporeal shock-wave lithotripsy rather than cholecystectomy is projected to result in an average gain of only 3 days of life and an average increase in direct medical charges of $1729 over 5 years of follow up. The resulting marginal cost-effectiveness of extracorporeal shock-wave lithotripsy vs. cholecystectomy is $216,000 of extra charges per year of life gained with extracorporeal shock-wave lithotripsy. Extracorporeal shock-wave lithotripsy is projected to be much more cost-effective for elderly than for young patients (10-20-fold difference), but considerably less cost-effective for multiple stones than a single stone (2-4-fold difference), and less cost effective for women than men (twofold difference). Adjusting for effects of morbidity on quality of life, extracorporeal shock-wave lithotripsy is projected to have slightly better quality-adjusted survival than cholecystectomy for the small subset of patients with one stone (by 8 to 43 days at 5 years) but not for young patients with multiple stones. It is concluded that decisions about appropriate use of extracorporeal shock-wave lithotripsy should consider the effects of patient characteristics on clinical and economic outcomes. PMID- 1904377 TI - Reproducibility of measurements of trace gas concentrations in expired air. AB - Measurement of the pulmonary excretion of trace gases has been used as a simple means of assessing metabolic reactions. End alveolar trace gas concentration, rather than excretory rate, is usually measured. However, the reproducibility of this measurement has received little attention. In 17 healthy subjects, duplicate collections of alveolar air were obtained within 1 minute of each other using a commercially available alveolar air sampler. The concentrations of hydrogen, methane, carbon monoxide, and carbon dioxide were measured. When the subject received no instruction on how to expire into the device, a difference of 28% +/- 19% (1SD) was found between duplicate determinations of hydrogen. Instructing the subjects to avoid hyperventilation or to inspire maximally and exhale immediately resulted in only minor reduction in variability. However, a maximal inspiration held for 15 seconds before exhalation reduced the difference to a mean of 9.6% +/ 8.0%, less than half that observed with the other expiratory techniques. Percentage difference of methane measurements with the four different expiratory techniques yielded results comparable to those obtained for hydrogen. In contrast, percentage differences for carbon monoxide measurements were similar for all expiratory techniques. When normalized to a PCO2 of 5%, the variability of hydrogen measurements with the breath-holding technique was reduced to 6.8% +/ 4.7%, a value significantly lower than that obtained with the other expiratory methods. This study suggests that attention to the expiratory technique could improve the accuracy of tests using breath hydrogen measurements. PMID- 1904380 TI - Ursodeoxycholic acid for the treatment of home parenteral nutrition-associated cholestasis. A case report. AB - Severe cholestasis associated with long-term home parenteral nutrition is rare, and no treatment is known to be effective. This study shows a case of a patient who developed jaundice while receiving long-term home parenteral nutrition. Causes of jaundice, other than the patient's parenteral feedings, were excluded. The patient's jaundice did not respond to alterations in his parenteral feeding program or to metronidazole. Ursodeoxycholic acid (600 mg/day) led to a prompt and sustained improvement in his hyperbilirubinemia. When ursodeoxycholic acid was stopped, the patient again became jaundiced, but this resolved with reinstitution of ursodeoxycholic acid. This case suggests that ursodeoxycholic acid may be an effective treatment for home parenteral nutrition--associated cholestasis and should be evaluated further in patients with cholestasis associated with parenteral feeding. PMID- 1904379 TI - Acute intestinal injury induced by acetic acid and casein: prevention by intraluminal misoprostol. AB - Acute injury was established in anesthetized rabbits by intraluminal administration of acetic acid with and without bovine casein, into loops of distal small intestine. Damage was quantified after 45 minutes by the blood-to lumen movement of 51Cr-labeled ethylenediaminetetraacetic acid (EDTA) and fluorescein isothiocyanate-tagged bovine serum albumin as well as luminal fluid histamine levels. The amount of titratable acetic acid used to lower the pH of the treatment solutions to pH 4.0 was increased by the addition of calcium gluconate. Luminal acetic acid caused a 19-fold increase in 51Cr-EDTA accumulation over saline controls; casein did not modify this effect. In saline controls, loop fluid histamine levels bordered on the limits of detection (1 ng/g) but were elevated 19-fold by acetic acid exposure and markedly increased (118-fold) by the combination of acid and casein. Intraluminal misoprostol (3 or 30 micrograms/mL), administered 30 minutes before acetic acid, significantly attenuated the increase in epithelial permeability (luminal 51Cr-EDTA, fluorescein isothiocyanate-bovine serum albumin accumulation) and histamine release (P less than 0.05). Diphenhydramine, alone or in combination with cimetidine, and indomethacin (5 mg/kg IV) were not protective. It is concluded that exposure of the epithelium to acetic acid promotes the transepithelial movement of casein leading to enhanced mast cell activation and mucosal injury. Damage to the epithelial barrier can be prevented by misoprostol. PMID- 1904381 TI - The effect of elemental diet on intestinal permeability and inflammation in Crohn's disease. AB - This study examines whether treatment of acute Crohn's disease with an elemental diet improves intestinal integrity and inflammation as assessed by a 51Cr-labeled ethylenediaminetetraacetatic acid (EDTA) permeability test and the fecal excretion of 111In-labeled autologous leukocytes, respectively. Thirty-four patients with active Crohn's disease completed a 4-week treatment course with an elemental diet. Active disease was characterized by increased intestinal permeability [24-hour urine excretion of orally administered 51Cr-EDTA, 6.4% +/- 0.6% (mean +/- SE); normal, less than 3.0%] and by high fecal excretion of 111In labeled leukocytes (14.2% +/- 1.1%; normal, less than 1.0%). Twenty-seven (80%) went into clinical remission, usually within a week of starting treatment. After 4 weeks of treatment, there was a significant decrease in both the urine excretion of 51Cr-EDTA (to 3.4% +/- 0.5%; P less than 0.01) and the fecal excretion of 111In (to 5.7% +/- 1.0%; P less than 0.001), indicating that such treatment is not just symptomatic. A framework for the mechanism by which elemental diet works, centering around the importance of the integrity of the intestinal barrier function, is proposed, and also appears to provide a logical explanation for some relapses of the disease. PMID- 1904382 TI - The 20 kDa C-terminally truncated form of pertussis toxin subunit S1 secreted from Bacillus subtilis. AB - The subunit S1 of pertussis toxin (PT) was purified as the recombinant product BacS1 from the culture supernatant of a Bacillus subtilis strain containing a secretion vector with a DNA fragment coding for the mature subunit S1 inserted downstream of the signal sequence of the alpha-amylase gene. The method of purification was successive ion exchange and adsorption chromatography. BacS1 occurred in two forms (28 and 20 kDa) of which the truncated 20-kDa peptide was the main one in the supernatant. The truncated BacS1 was purified and shown to have the same NH2-terminus as the full-size (28 kDa) BacS1. It was also enzymatically active indicating correct conformation. The truncated BacS1 was also shown to elicit neutralizing and protective antibodies when injected into mice or rabbits. PMID- 1904383 TI - Cloning and characterization of a DNA fragment that complements the nfxB mutation in Pseudomonas aeruginosa PAO. AB - The 2.2-kilobase DNA fragment that can complement the nfxB mutation in Pseudomonas aeruginosa PAO was cloned from chromosomal DNA of P. aeruginosa PAO1. The nfxB mutants show an increase in resistance to quinolones and hypersusceptibility to beta-lactam and aminoglycoside antibiotics. In the mutants, a 54 kDa outer membrane protein newly appeared. The phenotype was restored to the wild-type by transformation with plasmid carrying the 2.2-kb DNA fragment. PMID- 1904384 TI - Complex pattern of immunoglobulin mu gene expression in normal and transgenic mice: nonoverlapping regulatory sequences govern distinct tissue specificities. AB - Analysis of normal mice and transgenic mice carrying a rearranged immunoglobulin mu gene revealed a more complex tissue-specific pattern of mu gene expression than anticipated from previous observations. Expression of the endogenous mu locus and the mu transgene was detected both in lymphoid tissues and in skeletal muscle. Analysis of the expression pattern of mu transgenes containing intragenic deletions or point mutations in binding sites for Oct transcription factors (OCTA sites) indicated that distinct regulatory sequences control lymphoid- and muscle specific mu gene expression. Consistent with previous transfection experiments, mu gene expression in lymphoid tissues is dependent on the intragenic enhancer and the OCTA site in the promoter. However, neither of these regulatory sequences is required for mu gene expression in skeletal muscle that is governed by a muscle-specific control region located 3' of the enhancer. An "off-state" of the mu transgene was observed only in liver and embryonal fibroblasts, whereas enhancer-dependent mu transgene expression was detected at low levels in other nonlymphoid tissues. From these data we suggest a model for the regulation of tissue-specific mu gene expression in which a "ubiquitous" competence for basal transcription is up-regulated in lymphoid and muscle tissues by distinct cell type-specific regulatory sequences and down-regulated in liver and fibroblastic cells by putative negative sequence elements. PMID- 1904385 TI - Gamma-interferon induces differential expression of HLA-DR, -DP and -DQ in human ciliary epithelial cells. AB - The antigen-specific activation of T-helper lymphocytes is dependent on the presentation of antigen in context with the gene products of the major histocompatibility complex class II (MHC II). Aberrant expression of MHC II on the ciliary epithelium has been observed in uveitic eyes which may enable these cells to specifically interact with lymphocytes and may play a role in ocular autoimmunity. Human MHC II consists of three subclasses termed HLA-DR, -DP and DQ, which seem to be differentially regulated and may have different functions. The present study was initiated to investigate the dynamics of the differential MHC II expression on cultured human non-pigmented ciliary epithelial cells (NPE cells) in response to gamma-interferon (gamma-IFN) by means of immunohistochemistry. NPE cells grown in control tissue-culture medium did not express MHC class II. HLA-DR and -DP could be induced by incubation with 100 mu/ml gamma-IFN for 3 days. HLA-DQ was expressed only weakly and at higher doses of gamma-IFN (greater than or equal to 500 mu/ml) and longer incubation periods (greater than or equal to 5 days). After removal of the gamma-IFN stimulus, all three MHC II subclasses persisted for several days. The differential expression of HLA-DR and -DP as compared with HLA-DQ in response to gamma-IFN in the ciliary epithelium is similar to observations in other non-lymphoid ocular cells but appears to be different from the regulation of MHC II expression on lymphoid cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1904386 TI - Content and boundaries of medicine in long-term care: physicians talk about stroke. AB - Twenty physicians were interviewed about roles, treatments, goals, and relationships with older patients, especially stroke patients. Findings from this descriptive, anthropological investigation address the problem of congruence between needs and existing services, and in doing so, recast the ongoing debate about the medicalization of long-term care. This study emphasized the nonmedical features of geriatric medicine in general and stroke care in particular. In many instances, these physicians attempt to bridge gaps between medical and emotional needs and clinical and social services with social and psychotherapeutic as well as biomedical interventions. Because we found physicians' activities with stroke patients to be so broadly construed, treatment and management of stroke may be seen as paradigmatic for the role of physicians in long-term care. PMID- 1904387 TI - Tarsius dianae: a new primate species from central Sulawesi (Indonesia). PMID- 1904388 TI - Similarities in Aegyptopithecus and Afropithecus facial morphology. AB - Recently discovered cranial fossils from the Oligocene deposits of the Fayum depression in Egypt provide many details of the facial morphology of Aegyptopithecus zeuxis. Similar features are found in the Miocene hominoid Afropithecus turkanensis. Their presence is the first good evidence of a strong phenetic link between the Oligocene and Miocene hominoids of Africa. A comparison of trait lists emphasizes the similarities of the two fossil species, and leads us to conclude that the two fossil genera share many primitive facial features. In addition, we studied facial morphology using finite-element scaling analysis and found that the two genera show similarities in morphological integration, or the way in which biological landmarks relate to one another in three dimensions to define the form of the organism. Size differences between the two genera are much greater than the relatively minor shape differences. Analysis of variability in landmark location among the four Aegyptopithecus specimens indicates that variability within the sample is not different from that found within two samples of modern macaques. We propose that the shape differences found among the four Aegyptopithecus specimens simply reflect individual variation in facial characteristics, and that the similarities in facial morphology between Aegyptopithecus and Afropithecus probably represent a complex of primitive facial features retained over millions of years. PMID- 1904389 TI - International health spending: issues and trends. PMID- 1904390 TI - National health care spending, 1989. PMID- 1904392 TI - Supporting states' efforts to provide long-term care insurance. PMID- 1904391 TI - Public/private partnerships: a new approach to long-term care. PMID- 1904393 TI - Health care and American business: one CEO's view. Interview by John K. Iglehart. PMID- 1904394 TI - Synaptophysin in human breast carcinomas. AB - Synaptophysin expression was studied immunohistochemically in 109 female and in three male breast carcinomas. Positivity was demonstrated in 10 female and in two male tumours in a high percentage of neoplastic cells. Synaptophysin positive breast carcinomas also expressed other neuroendocrine markers such as chromogranin and neuron-specific enolase. PMID- 1904395 TI - G protein Gs alpha (GNAS 1), the probable candidate gene for Albright hereditary osteodystrophy, is assigned to human chromosome 20q12-q13.2. AB - Guanine nucleotide-binding proteins, also known as G proteins, mediate intracellular responses to a wide variety of extracellular stimuli. A variety of genes that specify the synthesis of the components of guanine nucleotide proteins have been identified. One of these proteins, termed Gs alpha (GNAS1), is the G protein component of the olfactory signal transduction cascade. Mutations in the GNAS1 gene leading to Gs alpha protein deficiency are known to be associated with pseudohypoparathyroidism Ia (Albright hereditary osteodystrophy) and certain pituitary tumors with acromegaly. Studies on the human--mouse somatic cell hybrids provisionally assigned this gene to chromosome 20. We have now confirmed this localization on chromosome 20 and regionally assigned the GNAS1 gene to 20q12-q13.2 by in situ hybridization. PMID- 1904396 TI - Nonhomologous recombination in the human genome: deletions in the human factor VIII gene. AB - Four deletions in the human factor VIII gene have been characterized at the sequence level in patients with hemophilia A. Deletion JH 1 extends 57 kb from IVS 10 to IVS 18. Intron 13 and exon 14 are partially deleted in patients JH 7 and JH 37, with a loss of 3.2 and 2.4 kb of DNA, respectively. The 3' deletion breakpoint of the JH 21 event resides in intron 3 and extends 5' into intron 1, resulting in the loss of exons 2 and 3. Seven of the eight breakpoints sequenced (5' and 3' for each of the four deletions) occur in nonrepetitive sequence, while the 3' breakpoint of the JH 1 resides in an Alu repetitive element. All of the deletions are the result of nonhomologous recombination. The 5' and 3' breakpoints of JH 1, JH 7, and JH 37 share 2- to 3-bp homologies at the deletion junctions. In contrast, two nucleotides have been inserted at the JH 21 deletion junction. Short sequence homologies may facilitate end-joining reactions in nonhomologous recombination events. PMID- 1904397 TI - Detection of human cytokine-secreting cells in distinct anatomical compartments. PMID- 1904398 TI - Fluorescence-based monitoring of interleukin-2 gene expression. PMID- 1904399 TI - Activation of mouse peritoneal macrophages by maintenance in serum-free medium. AB - Normal mouse peritoneal macrophages maintained in a serum-free medium for 48-72 h and then stimulated with phorbol myristate acetate, zymosan or bacteria, released large amounts of hydrogen peroxide. Opsonized zymosan and bacteria stimulated greater release than their unopsonized counterparts. Enhanced peroxide production was not a consequence of increased uptake of particles. Addition of serum to the serum-free medium abolished activation. The addition of interferon-gamma to the serum-free medium enhanced the effect of the serum-free treatment of macrophages from C3H/HeJ mice but abolished the effect of serum free treatment of macrophages from CFLP mice. The results are discussed in terms of negative regulation of receptor-oxidase linkage by serum. PMID- 1904400 TI - Disodium cromoglycate enhances ongoing immunoglobulin production in vitro in human B cells. AB - The effect of disodium cromoglycate (DSCG) upon human immunoglobulin (Ig) isotypes and IgG subclasses production by purified B cells was studied. DSCG enhanced IgM, IgG1, IgG2, IgG3, IgG4 and IgA production in a dose-dependent fashion, while DSCG failed to induce IgE production at any concentrations tested by purified B cells. When B cells were separated into small resting and large activated B cells, DSCG failed to induce Ig production from small resting B cells in the presence or absence of Staphylococcus aureus Cowan strain I (SAC). In contrast, in large activated B cells DSCG significantly enhanced all types of Ig production (two-to threefold), especially IgG4 production (seven-to 11-fold), except IgE, which large B cells did not produce. The enhancement of IgG subclass production was not subclass switching, since DSCG failed to enhance IgG1 production in B cells depleted of surface IgG1+ cells (sIgG1+ cells). Similarly, DSCG did not enhance IgG2, IgG3 or IgG4 production from sIgG2-, sIgG3- or sIgG4- B cells, respectively, Interleukin-4 (IL-4) or interleukin-6 (IL-6) also enhanced Ig production except IgG4 from large activated B cells. The enhancing effect of DSCG was not mediated by IL-4 or IL-6 since anti-IL-4 or anti-IL-6 antibody failed to block the DSCG-induced enhancement. DSCG also enhanced IgG2 and IgM production from human B-cell lines GM-1500 and CBL, respectively. These results suggest that DSCG directly and preferentially stimulates activated B cells which are producing Ig and, in addition, enhances their Ig production. PMID- 1904402 TI - The effect of transfected MHC class I genes on sensitivity to natural killer cells. AB - To test the hypothesis that major histocompatibility complex (MHC) molecules protect target cells from lysis by natural killer cells (NKC), we transfected the MHC- B16 melanoma line F10 with the class I genes encoding Dd, Kb, and Kk. Only low levels of Dd expression could be obtained and there was no protection against NKC. By contrast, Kb and Kk transfectants were obtained which displayed significant resistance to NKC, and with the latter transfectants resistance was clearly related to the level of transgene expression. Various mutants of the F10 line with altered patterns of MHC expression were also obtained. These mutant lines provided evidence that (i) the Db molecule is also capable of inducing resistance to NKC and (ii) high MHC class I expression does not by itself guarantee lowered susceptibility to NKC. PMID- 1904403 TI - Dopaminergic abnormalities in borderline essential hypertensive patients. AB - To explore whether an altered metabolic pathway of dihydroxyphenylalanine (DOPA) may be related to some previously observed dopamine abnormalities in borderline hypertension, we measured basal and DOPA-induced (500 mg orally) changes in blood pressure and pulse rate as well as in three hourly plasma and urine samples. We found that borderline hypertensive patients compared with controls 1) showed a higher baseline urinary excretion of methoxytyramine, a marker of exocytotic dopamine release, with a greater DOPA-induced decrease of systolic blood pressure without reflex tachycardia; 2) had in response to DOPA a blunted plasma DOPA and free dopamine increase but an accentuated plasma dopamine sulfate and urinary DOPAC excretion; and 3) eliminated comparable quantities of dopamine in urine despite a lower rise in the glomerular DOPA load. Furthermore, although DOPA elicited natriuresis in both groups, its effect was greater in borderline hypertensive patients, who lacked the urinary sodium correlation with urinary dopamine excretion seen in control subjects. These data are compatible with increased basal exocytotic dopamine release and accelerated neuronal and renal (extraneuronal) dopamine generation from administered DOPA in borderline hypertension. The DOPA-induced hypernatriuresis exceeding augmented dopamine in borderline hypertensive patients, contrasting with the urinary sodium and dopamine correlation in control subjects, suggests that DOPA induced an additional natriuresis in borderline hypertensive patients by a decrease in renal sympathetic tone because of its central inhibition of sympathetic outflow, which also may account for the absence of reflex tachycardia. PMID- 1904401 TI - H-2 (I-A) control of the antibody repertoire to secreted antigens of Trichinella spiralis in infection and its relevance to resistance and susceptibility. AB - Humans infected with the parasitic nematode Trichinella spiralis vary in the specificity of their antibody responses to the antigens of the parasite. The possibility that such host variation in antigen recognition has a genetic basis was examined in infected inbred mice whose antigen recognition profiles were characterized by immunoprecipitation of biosynthetically labelled secreted materials of adult parasites and SDS-PAGE. The strains varied considerably in repertoire and none produced detectable antibody to all the potential antigens. Using a panel of H-2 congenic and recombinant strains it was established that the repertoire was determined by the major histocompatibility complex (MHC), the I-A region in particular. Other factors, such as level of infection and variation between individuals, affected antigen recognition profiles, but this was always within limits imposed by the MHC. Lastly, an attempt to correlate antibody repertoire with relative susceptibility or resistance to T. spiralis failed to reveal any clear association. This also applied to the AKR/J and AKR-Fv-1b strains, which are H-2-identical but differ in a non-MHC susceptibility locus. These findings would argue, therefore, that the I-A region controls the antibody repertoire in this nematode infection but that the repertoire overall has little influence on the efficiency with which the infections are controlled by the immune system. Should this also apply for other nematode infections, then antigen recognition profiles of infected individual humans and domestic animals might not, therefore, be useful indicators of relative resistance or susceptibility to infection. PMID- 1904404 TI - Plasminogen activator inhibitor 1 in human carcinoma tissues. AB - The content of PAI-I was measured in carcinoma tissues from the stomach and colorectum divided macroscopically into 3 portions: the central part of the carcinoma, the marginal part of the carcinoma containing some normal mucosa, and the normal mucosa. Among these tissues, the highest levels of PAI-I antigen were found in the central part of the carcinoma. On the other hand, no PAI-I antigen or activity was observed in the normal mucosae. The PAI-I produced in the stomach and colorectal carcinoma tissues showed a non-lytic zone with a molecular weight of 54 kDa by reverse fibrin autography, and this 54-kDa band reacted with anti PAI-I IgG on an immunoblotted nitrocellulose membrane by the avidin-biotin complex method. The contents of PAI-2 in the carcinoma tissues were not significantly different from those in the normal mucosa of the stomach and colorectum. In both the stomach and colorectal carcinomas, the highest value of u PA/total PA (sum of u-PA and t-PA) was observed in the central part of the carcinoma, followed by the marginal part of the carcinoma, and was lowest in the normal mucosa. We conclude that increased levels of PAI-I in malignant tissue of the stomach and colorectal tract may serve to modulate extra-cellular proteolysis by u-PA. PMID- 1904405 TI - Suppression of the translocated myc gene and expression of intracisternal A particle genes in tumorigenic and non-tumorigenic hybrids between murine myeloma and normal fibroblasts. AB - We have studied the tumorigenic potential of a series of independent intraspecies hybrid clones derived from fusion of murine myeloma (BALB/c) and normal fibroblasts (C3H). All of these hybrids grew as adherent cells and thus resembled the fibroblast phenotype. As judged by chromosome enumeration, these hybrids appear to retain the full complement of their parental cells. Three out of 4 hybrids tested were able to form colonies in soft agar and to grow as tumors in either nude or (BALB/c x C3H) F1 mice, albeit at a reduced rate. The 4th hybrid did not grow in agar, was non-tumorigenic and may have had a 2:1 fibroblast to myeloma genomic equivalence ratio. In contrast to the parental myeloma cells, all the hybrids exhibited restricted growth rates in serum-free medium. As in our previous sets of hybrids formed between myeloma and L-cells, expression of the Ig genes was inhibited in the new hybrids and the derived tumors. The constitutive expression of the translocated myc gene in the myeloma parental cells was decreased in the hybrids and in all their derived tumors. In contrast, all of the hybrid cell lines and the tumors express high levels of the intracisternal A particle mRNAs. Our results show that the tumorigenic phenotype of myeloma cells is either fully or partially suppressed in myeloma x fibroblast hybrids and that this may be due to the fact that expression of the translocated c-myc is suppressed. We suggest that, in addition to the translocated myc gene, myeloma cells contain other activated oncogene(s), and that the latter are responsible for the residual tumorigenic potential of the myeloma x fibroblast hybrids. PMID- 1904406 TI - Degradation of growth hormone releasing factor analogs in neutral aqueous solution is related to deamidation of asparagine residues. Replacement of asparagine residues by serine stabilizes. AB - The incubation of a solution of the human growth hormone releasing factor analog, [Leu27] hGRF(1-32)NH2 at pH 7.4 and 37 degrees, resulted in extensive degradation of the sample. The major degradation products were identified as the peptides [beta-Asp8, Leu27] hGRF(1-32)NH2 and [alpha-Asp8, Leu27] hGRF(1-32)NH2, produced by deamidation of the Asn8 residue. When tested as growth hormone (GH) secretagogues in cultured bovine anterior pituitary cells, [beta-Asp8, Leu27] hGRF(1-32)NH2 was estimated to be 400-500 times less potent than the parent Asn8 peptide, while [alpha-Asp8, Leu27] hGRF(1-32)NH2 was calculated to be 25 times less potent than the parent Asn8 peptide. Three additional analogs of [Leu27] hGRF(1-32)NH2 containing either Ser or Asn at positions 8 and 28 were prepared and evaluated for their GH releasing activity and stability in aqueous phosphate buffer (pH 7.4, 37 degrees). Based on disappearance kinetics, [Leu27] hGRF(1 32)NH2 had a half-life of 202 h while the other analogs had the following half lives: [Leu27, Asn28] hGRF(1-32)NH2 (150 h); [Ser8, Leu27, Asn28] hGRF(1-32)NH2 (746 h); and [Ser8, Leu27] hGRF(1-32)NH2 (1550 h). After 14 days, incubated samples of the Asn8 analogs lost GH releasing potency, while the Ser8 analogs retained full potency. The potential for loss of biological activity brought about by deamidation of other engineered peptides and proteins should be considered in their design. PMID- 1904407 TI - A new synthetic functionalized antigen carrier. AB - A new synthetic functionalized antigen carrier is described. It consists of a core of seven branched lysine residues, of which each of the four N-terminal lysine residues contains two N-(S-acetylmercaptoacetyl)-glutamyl residues. After removal of the protecting S-acetyl groups affording eight thiol functions, the carrier can easily be conjugated to a properly functionalized antigen, e.g. an S (Npys)-cysteinyl peptide, thus affording a high molecular weight conjugate with an unusually high antigen content. PMID- 1904408 TI - The "nasal cycle" in infants. AB - In 93 of 100 infants there was a marked difference in the measured end-tidal carbon dioxide (CO2) level between nasal airways during quiet sleep (4.88 Kpa V 3.3 Kpa P less than 0.001). It is suggested that partial nasal obstruction is common in infants. Nasal airway resistance is increased by mucosal swelling, is assymetric, regularly alternates between sides (the nasal cycle), and is under autonomic control. End tidal carbon dioxide values are widely measured as part of an assessment of respiratory control and risk of sudden infant death syndrome. The preferential use of one nasal airway must be taken into account in assessing such results. PMID- 1904409 TI - Radiotherapy of T1 glottic cancer with 6 MeV X rays. AB - We treated 154 patients with T1 glottic carcinoma with 6 MeV X rays through 16 cm2 parallel-opposing open fields on a free set-up delivering a median dose of 67 Gy in 6 2/3 weeks. Observed and relative 5-year survival rates for all patients were 87% and 100%, respectively. The local control rate at 5 years was 89%. Of 18 patients who clinically had local recurrence, 17 were salvaged by a secondary treatment. There were no complications requiring medical or surgical attention. A tendency toward increasing local control rates with increasing total doses was observed in the range between 57.5 Gy and 72.5. No significant correlation was found between local control rates and field size, daily dose, or the technique used. A tendency toward a lower local control rate was noted for patients whose anterior commissures were grossly involved; however, it is not known if this could be attributed to the use of 6 MeV X rays. The results are comparable to those obtained with 60Co as reported in the literature. It is concluded that 6 MeV X rays on a free set-up delivering 65-70 Gy in 6 1/2-7 weeks can be used satisfactorily for the treatment of early glottic carcinoma. PMID- 1904410 TI - Tumor-targeted delivery of 8-hydroxyquinoline. AB - RIF-1 mouse tumors express high levels of beta-glucuronidase activity relative to most normal tissues. The high activity can be exploited for targeting specific drugs preferentially to tumor tissues. In this study we examined the kinetics of 8-hydroxyquinoline (8-OHQ) accumulation in tumor and in several normal tissues resulting from the in vivo deconjugation of 8-hydroxyquinolyl-glucuronide (8-OHQ GlcA). Tumors were acidified with D-glucose and NaHCO3 prior to the administration of 8-OHQ-GlcA; subsequently the deconjugated aglycone, 8-OHQ, accumulated preferentially in tumors and reached peak levels between 30 and 60 min after the 8-OHQ-GlcA injection. Mild hyperthermia of 30 min at 43 degrees C to the tumors further increased their peak 8-OHQ levels by a factor of 2-3. Some normal tissues, mostly kidney, liver, and colon, also accumulated 8-OHQ, but the aglycone appeared early in the normal tissues (near 30 min post-injection) and was significantly reduced by 60 min when 8-OHQ remained high in the tumor. Administration of 8-OHQ-GlcA alone, without prior tumor acidification, failed to produce measurable accumulations of 8-OHQ in tumors and in normal tissues. Tissue clearance of 8-OHQ is mediated primarily by the enzymatic reconjugation of 8-OHQ via UDP-glucuronosyltransferase (UDPGT). UDPGT activity was high in liver, kidney, and bowel, but low in the RIF tumor, spleen, muscle, and brain. Hyperthermia had only a modest effects on UDPGT activity: a heat dose of 30 min at 45 degrees C reduced activity less than 60%. Thus, preferential accumulation and prolonged retention of 8-OHQ in RIF tumors may be caused by a combination of factors: a) high tumor beta-glucuronidase activity, b) selective tumor acidification during hyperglycemia, c) low tumor UDPGT activity, and d) other factors, such as tumor blood flow. PMID- 1904411 TI - Evaluation of radiosurgery techniques with cumulative dose volume histograms in linac-based stereotactic external beam irradiation. AB - Radiosurgery at UCSF is performed with a 6-MV linear accelerator with tertiary collimation for improved small field definition. The dose delivery to the target relative to normal tissue is influenced by the number of arcs, the arc geometry, field size, and beam energy. The impact of arc number, arc geometry, and field size on the dose distribution from 6-MV X rays in a 16 cm spherical phantom has been evaluated through the use of cumulative dose volume histograms. Dose volume histograms were calculated for a) 1-5 and 10 arcs, and b) collimator sizes of 1.25, 2.0, and 3.0 cm. Differences between techniques were found at the 5-10% level for field sizes from 1.25 to 2.0 cm. It was shown that the finite dimension of the sphere and, by extension, head diminishes the differences between techniques for the larger field sizes. The effect of treating with two isocenters is also analyzed and an approach for improving the dose distribution is presented. PMID- 1904412 TI - Physical aspects of the angle-beta concept in electron arc therapy. AB - A technique for the determination of treatment parameters that are required to achieve a desired depth dose distribution in electron arc therapy is discussed and a method for calculating isodose distributions is presented. Both the treatment technique and the dose calculation method rely on the angle beta concept, which uniquely describes the dependence of the radial percentage depth doses in electron arc therapy on the nominal field width, isocenter depth, and virtual source-axis distance. The angle beta concept is discussed in detail and the electron pseudo-arc therapy technique used at McGill is described. Also presented is the method used to achieve dose homogeneity in target volumes treated with the pseudo-arc technique. PMID- 1904413 TI - The travail and triumph of Sidney Greenspan. AB - The question of whether a feeding-tube could be withdrawn from Sidney Greenspan, a man who had survived in a Chicago nursing home for six years in a vegetative state, has focused ethical and legal deliberation on the issue of whether Illinois will follow the tradition of cases of court-sanctioned withdrawal (Quinlan, Fox, Conroy, Jobes, et al) or the more ambiguous precedents of Longeway and Cruzan, which disallowed withdrawal. PMID- 1904414 TI - Induction of intestinal adenocarcinomas by 2-amino-1-methyl-6-phenylimidazo[4,5 b]pyridine in Nagase analbuminemic rats. AB - 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), the most abundant mutagenic heterocyclic amine in cooked foods, was examined for carcinogenic potential using Nagase analbuminemic rats (NARs), which are sensitive to various carcinogens. The concentration of PhIP in the diet was 0.04% at the beginning of the experiment, this being subsequently gradually reduced to 0.01% to avoid severe body weight loss. Ten of 13 treated NARs developed a total of 36 intestinal tumors within the 311-day experimental period. Among these, 22 were adenocarcinomas and 2 were adenomas of the small intestine, 4 were adenocarcinomas of the cecum and 8 were adenocarcinomas of the large intestine. The results suggest that PhIP could represent a significant risk to human populations exposed to foods containing heterocyclic amines. PMID- 1904415 TI - Improvement of gelatin particle agglutination test for detection of anti-HTLV-I antibody. AB - Partial modifications of antigen components were made to improve the gelatin particle agglutination (PA) test for the detection of antibodies against human T cell leukemia virus type-I. Envelope glycoproteins prepared by lentil lectin affinity chromatography were further added to the purified viral antigens to be coated on the gelatin particles. Comparative studies with a conventional PA test kit (Serodia ATLA) and indirect immunofluorescence assay showed that the specificity and sensitivity of the new PA test were increased and that abnormal agglutination such as the prozone phenomenon was abolished by this improvement. PMID- 1904416 TI - Overexpression of c-Myc inhibits the appearance of a specific DNase I hypersensitive site in the beta-globin chromatin in murine erythroleukemia cells. AB - To investigate the molecular mechanism of regulation of differentiation by c-Myc, we examined the acquisition of DNase I hypersensitivity by beta-globin chromatin in an MEL cell transformant (38-2) in which the c-myc gene was placed under the control of a metallothionein gene promoter. Of the three DNase I hypersensitive sites around the beta-globin gene which were detected in MEL cells after DMSO treatment, the appearance of a specific DNase I hypersensitive site near the promoter was greatly reduced by the overexpression of c-Myc. This result suggests that c-Myc regulates beta-globin expression by interfering with the establishment of an active chromatin conformation around the beta-globin gene. PMID- 1904417 TI - Quantitative risk assessment of carcinogenicity of urethane (ethyl carbamate) on the basis of long-term oral administration to B6C3F1 mice. AB - A carcinogenicity study of urethane was performed for quantitative assessment of its risk in humans. Three hundred 6-week-old male B6C3F1 mice were divided into 6 groups, each consisting of 50 mice, and urethane was given ad libitum in drinking water at levels of 0 (control), 0.6, 3, 6, 60 and 600 ppm for 70 weeks. The tumors with a clear dose-response relationship were lung tumor (alveolar/bronchiolar adenoma or carcinoma) and liver tumor (hemangioma or angiosarcoma). The incidences of these two types of tumor were applied to estimation of the virtually safe dose (VSD) at the level of 10(-6) by using four mathematical models (Logit, Probit, Weibull and Multistage models). The VSD based on the incidences of lung tumor by using the Logit model was estimated to be 1.8 x 10(-4) mg/kg body weight/day. On the other hand the VSD based on those of liver tumor by using the Weibull model was 7.2 x 10(-5) mg/kg body weight/day. Thus, the VSDs based on the incidences of the two different types of tumor using the most compatible mathematical model in each case, as judged from the P-values, were similar. PMID- 1904418 TI - Inhibitory effect of 2-O-octadecylascorbic acid in agglutination assay with concanavalin A; short-term examination of rat urinary bladder carcinogenesis. AB - A derivative of ascorbic acid, 2-O-octadecylascorbic acid (CV-3611), is a strong scavenger of active oxygen species. We examined the effect of CV-3611 on a short term test of bladder carcinogenesis, using concanavalin A (Con A)-dependent agglutination of isolated bladder epithelial cells. Rats were given 0.01% N-butyl N-(4-hydroxybutyl)nitrosamine (BHBN) for 1 week, and then 5% sodium saccharin or 2% DL-tryptophan or 0.01% BHBN alone or with 0.002, 0.006 or 0.02% CV-3611 for 3 weeks. Treatment with CV-3611 reduced the effects of the bladder tumor promoters sodium saccharin and DL-tryptophan by 48-86 and 65-87%, respectively. CV-3611 also reduced the number of aggregates of bladder epithelial cells from rats treated with BHBN for 4 weeks. These results suggest that CV-3611 has a suppressive effect on rat bladder carcinogenesis. PMID- 1904419 TI - Enhancing effect of a choline-deficient diet on alterations of hepatic drug metabolizing enzymes in hepatitis- and hepatoma-predisposed rats (LEC rats). AB - Marked alterations of hepatic drug-metabolizing enzymes were observed in hepatitis- and hepatoma-predisposed rats (LEC rats) fed a choline-deficient diet. The diet enhanced the development of hepatitis with severe jaundice. The levels of two major classes of cytochrome P-450, P-450PB and P-450MC, were markedly decreased. GST-Yp was dramatically increased, whereas GST-Ya, Yb1 and Yb2 were decreased. LEA rats (the control rats to LEC) fed a choline-deficient diet mimicked LEC rats fed a normal diet in terms of the above enzyme alterations, indicating that hypomethylation is involved in the pathogenesis of hepatitis and hepatoma in LEC rats. Such hypomethylation may initiate the hepatocytes that spontaneously develop hepatitis and hepatoma. PMID- 1904420 TI - Appearance of a carcinoid-like pattern in rat hepatic tumors induced by 3'-methyl 4-dimethyl-aminoazobenzene. AB - This study investigated the histological distribution of argyrophilic cells in experimental hepatic neoplasms, the number of these cells, and the proportion of neoplasms with such cells. Seventy 6-week-old male Donryu rats were given a 0.06% 3'-methyl-4-dimethyl-aminoazobenzene (3'-MeDAB) diet for 10 weeks, followed by an ordinary diet for an additional 10 weeks. Of the 70 rats, 50 were used for this investigation; 29 had hepatic tumors, 18 had cholangiofibrosis, and the other three had oval cell proliferation only. Hepatic tissues were stained with Grimelius and Fontana-Masson stains as well as routine hematoxylin-eosin stain. Argyrophilic cells were found in the hepatic neoplasms of 8 rats without argentaffin cells, while cholangiofibrosis was associated with argentaffin cells in almost all cases. Of the 8 rats with argyrophilic cells, three had an abundant population of these cells. The argyrophilic cells were found in areas of the neoplasms with a glandular, trabecular, tubular, or poorly differentiated pattern. Electron microscopy revealed that the neoplastic cells with a positive argyrophil reaction contained small round electron-dense endocrine granules. In addition, in the areas of cholangiofibrosis, two different types of gut endocrine cells were present (G and EC cells). These results suggest that 3'-MeDAB might induce hepatic carcinoid under certain conditions, though we have yet to confirm the development of a pure hepatic carcinoid due to this substance. PMID- 1904422 TI - Four forms of cytochrome P-450 in human fetal liver: purification and their capacity to activate promutagens. AB - Four forms of cytochrome P-450 were separated and purified to electrophoretic homogeneity from human fetal livers. These forms of cytochrome P-450, termed P 450HFLa, P-450HFLb, P-450HFLc and P-450HFLd, were distinguishable from each other in their molecular weights, spectral properties, immunochemical properties and mutagen-producing activities from promutagens. The molecular weights of P 450HFLa, b, c and d were estimated to be 51,500, 49,000, 51,500 and 50,000, respectively. Antibodies to P-450HFLa recognized P-450HFLc but not P-450HFLb or d, and antibodies to rat P-448-H (P-450IA2) cross-reacted with P-450HFLb but not with other forms of cytochrome P-450. The N-terminal amino acid sequence of P 450HFLc was highly homologous, but not identical, to that of P-450HFLa. Each form of cytochrome P-450 catalyzed mutagenic activation of aflatoxin B1 (AFB1), 2 amino-3-methylimidazo[4,5-f]quinoline (IQ) and 2-amino-6-methyldipyrido-[1,2 a:3',2'-d]imidazole (Glu-P-1) at different rates. P-450 HFLa showed activities to produce mutagen(s) from AFB1, IQ and to a lesser extent from Glu-P-1. P-450 HFLb activated IQ at a faster rate than did the other forms. P-450 HFLc produced a mutagen from AFB1 and Glu-P-1 but not from IQ. P-450 HFLd did not activate these promutagens at significant rates. PMID- 1904421 TI - Quantitative assay of epidermal growth factor receptor in human squamous cell carcinomas of the oral region by an avidin-biotin method. AB - A quantitative assay method for epidermal growth factor receptors (EGFRs) of human tumor tissues was established, based on enzyme-labeled avidin-biotin (LAB) interaction with anti-human EGFR monoclonal antibody 528IgG. A standard calibration curve for EGFR estimation in human tumor tissues was obtained with A431#8 cells cloned from A431 human epidermoid carcinoma cell line. The coefficient of variance for the standard curve was below 35% in the application to tumor tissues from nude mice implanted with human tumor cell lines. The minimum tissue amount required for the quantitative assay was around 0.1 g (wet weight). Using the LAB method, the correlation between the level of EGFR number and tumor malignancy was examined for 14 human squamous cell carcinomas (SCCs) from the oral region. Seven of the SCCs showed a more than two-fold higher EGFR number compared to normal gingival tissues. Three highly aggressive carcinomas with poor prognosis possessed five to ten times higher levels of EGFR number than normal tissues. The elevated EGFR level in the SCCs seems to correlate to increasing tumor size and the stage of SCCs as clinically classified according to the 1987 UICC TNM system. PMID- 1904423 TI - Sequence-dependent termination of mammalian DNA polymerase reaction by a new platinum compound, (-)-(R)-2-aminomethylpyrrolidine(1,1-cyclobutane dicarboxylato)-2-plati num(II) monohydrate). AB - We examined the mechanism of the inhibition of DNA synthesis by a new platinum compound, (-)-(R)-2-aminomethylpyrrolidine(1,1-cyclobutane-dicarboxylato+ ++)-2 platinum(II) monohydrate (DWA-2114R), a derivative of the antitumor drug cis diamminedichloroplatinum(II) (CDDP), using prokaryotic and eukaryotic DNA polymerases. Preincubating activated DNA with CDDP or DWA-2114R reduced its template activity for prokaryotic and eukaryotic DNA polymerases in a dose dependent manner. DWA2114R required six times greater drug concentration and two times longer incubation time to show the same decrease of the template activity compared to CDDP. Treatment of primed pUC118 ssDNA templates with the two drugs followed by second-strand synthesis by prokaryotic and eukaryotic DNA polymerases revealed that DWA2114R bound to DNA in a similar manner to CDDP and these adducts blocked DNA elongation by DNA polymerases of eukaryotes as well as of prokaryotes. With these two drugs, the elongations by E. coli DNA polymerase I (Klenow fragment), T7 DNA polymerase and calf thymus DNA polymerase alpha were strongly arrested at guanine-guanine sequences (GG). Stop bands were also observed at adenine-guanine sequences (AG) guanine-adenine-guanine sequences (GAG) and mono-guanine sequence (G). Calf testis DNA polymerase beta was also arrested efficiently at AG, GAG and G, but much more weakly at GG. This pattern was common to DWA2114R and CDDP. PMID- 1904424 TI - T cell receptor-independent cell-mediated cytotoxicity by nude mouse lymphokine activated killer cells. AB - Lymphokine-activated killer (LAK) cells, which can lyse a variety of tumor cells, can be induced from both normal and athymic nude mouse spleen cells by culture with high doses of recombinant interleukin 2 (rIL-2). LAK cells generated from nude mouse spleen cells (Nude-LAK cells) express just Thy 1.2 antigen, but not CD4 and CD8 antigens. Nude-LAK cells express neither T3 molecule, T cell receptor (TCR) alpha beta nor TCR gamma delta on their cell surface. The lack of TCR expression on Nude-LAK cells was confirmed by the results of northern blot analysis. LAK cells generated from normal mouse spleen cells (Nor-LAK) express TCR alpha, beta transcripts, while Nude-LAK cells express only sterile TCR beta transcript, but not TCR alpha transcript. TCR gamma delta transcripts were scarcely detected in both Nor-LAK cells and Nude-LAK cells. Thus, it is strongly suggested that Nude-LAK cells can recognize and lyse tumor cells by TCR independent mechanisms. Monoclonal antibody against lymphocyte function associated antigen (LFA-1) molecule can block the cytotoxicity of Nude-LAK cells, indicating an important role of such accessory molecules in Nude-LAK cell mediated cytotoxicity. PMID- 1904426 TI - Augmentation by tumor necrosis factor alpha of the systemic therapeutic effect of lymphokine-activated killer cells in adoptive immunotherapy of murine tumor. AB - The therapeutic effect of a combined modality of lymphokine-activated killer (LAK) cells and tumor necrosis factor alpha (TNF alpha) on MBL-2 tumor in C57BL/6 mice was studied. Murine LAK cells induced from splenocytes by interleukin 2 (IL2) could lyse MBL-2 target cells in vitro. but no enhancement of the LAK activity was found by the treatment of LAK cells with TNF alpha in vitro. However, the treatment of MBL-2 with TNF alpha enhanced the sensitivity to LAK cells. Moreover, administration of TNF alpha to mice bearing solid MBL-2 tumor led to increased tumor vascular permeability within 1 h, and resulted in the enhanced accumulation of systemically transferred LAK cells in tumor tissue. Based on these results, we treated MBL-2-bearing mice with TNF alpha and then with LAK cells 1 h later. No therapeutic effect was observed when tumor-bearing mice were treated with TNF alpha alone or LAK cells plus IL2. However, adoptive immunotherapy using LAK cells and TNF alpha had therapeutic effects, i.e., growth inhibition of tumor nodules and prolongation of survival. These results indicated that appropriately timed pretreatment of tumor-bearing mice with TNF alpha augmented the anti-tumor efficacy of LAK cells. PMID- 1904425 TI - Establishment of mouse lymphokine-activated killer cell clones and their properties. AB - To assess the properties of lymphokine-activated killer (LAK) cells, we established mouse LAK cell clones from LAK cell lines induced from C57BL/6 mouse spleen cells. Although these clones expressed similar phenotypes to the parent LAK cells, Lyt-2 was expressed in a restricted portion of the clones. All clones were found to express T3 CD2 and T cell receptor (TcR) alpha beta on their cell surface. Rearrangement patterns of TcR beta were the same among the clones derived from the same parent cell line but differed in those from different cell lines as determined by using C beta 1 and J beta 2 probes. The molecules responsible for LAK-target cell binding were examined by using a monoclonal antibody (mAb) against lymphocyte function associated antigen 1 (LFA-1). This mAb (termed KBA) showed inhibitory effects on both LAK-target cell binding and cytolytic activity of LAK cell clones, indicating a principal role of LFA-1 in LAK cell clones. The magnitude of perforin mRNA expression in LAK cell clones was unrelated to their cytolytic activities. PMID- 1904427 TI - The effect of interferon on carcinogenesis by N-ethyl-N'-nitro-N-nitrosoguanidine in the duodenum of mice. AB - The inhibitory effect of murine interferon alpha/beta (Mu-IFN) on the induction of adenocarcinoma of the duodenum in C57BL/6 mice given N-ethyl-N'-nitro-N nitrosoguanidine (ENNG) was examined. ENNG was given continuously in drinking water for 4 weeks and Mu-IFN was given intraperitoneally for 12 weeks. Then, the duodenal tumors of mice were examined stereomicroscopically and histologically. The level of IFN activity and natural killer (NK) activity were evaluated after an intraperitoneal single injection of Mu-IFN, and the level of NK activity was evaluated 2, 5 and 8 weeks after giving ENNG and Mu-IFN. In the mice given Mu IFN, the incidence of duodenal tumors was significantly decreased (P less than 0.01), compared with that in mice given ENNG alone. Further, anti-asialo GM1 was given intraperitoneally every 5 days for 8 weeks to depress NK function and the incidence and size of duodenal tumors were examined. The results indicated that NK cells also have an important effect on the process of carcinogenesis. These data suggest that chemoprevention with IFN may be feasible. PMID- 1904428 TI - Antitumor activity of fluoropyrimidines and thymidylate synthetase inhibition. AB - Experimental chemotherapy with 5-fluorouracil (5-FU; 60 mg/kg), 1-hexylcarbamoyl 5-fluorouracil (HCFU; 70 mg/kg), 3-(3-(6-benzoyloxy-3-cyano-2 pyridyloxycarbonyl)benzoyl)-1-ethoxym ethyl-5- fluorouracil (BOF-A2; 30 mg/kg) and UFT (20 mg/kg as tegafur with uracil at a molar ratio of 1:4) was performed using human gastric (H-111) and colon (Co-4) carcinoma strains in nude mice. 5-FU was administered ip with a q4d x 3 schedule and the other agents were given po daily for three weeks. Concentrations of 5-FU in the serum and the tumor were assessed by gas chromatography-mass fragmentography, two hours or 12 days (5-FU) after the last treatment, and thymidylate synthetase (TS) was assayed according to the method of Spears et al. using the same schedule. The antitumor activity of the agents was assessed in terms of the actual tumor weight at the end of the experiment. HCFU was effective against both strains and 5-FU was effective against Co-4, although the other agents were ineffective against either strain. Statistically significant correlations were found between the serum and tumor concentrations of 5-FU and antitumor activity. Statistically significant correlations were also observed between the antitumor activity and TS inhibition rate (TSIR) and the activity of free thymidylate synthetase (TSfree), with higher TSIR and lower TSfree resulting in higher antitumor activity. Therefore, TSIR and TSfree were thought to be promising indicators for predicting the antitumor activity of fluoropyrimidines. PMID- 1904429 TI - Genetic evidence for interaction of sigma A with two promoters in Bacillus subtilis. AB - The specificity of promoter binding by RNA polymerase is governed by the sigma subunit. Recent studies, in which single-amino-acid substitutions in sigma factors have been found to suppress the effects of specific base pair substitutions in promoters, support the model that these sigma factors make sequence-specific contacts with nucleotides at the -10 and -35 regions of promoters. We found that single-amino-acid substitutions in the putative -35 region and -10 region recognition domains of sigma A specifically suppressed the effects of mutations in the -35 and -10 regions, respectively, of two promoters that are expressed in exponentially growing Bacillus subtilis. These mutations change the specificity of sigma A, the primary sigma factor in growing B. subtilis, and demonstrate that this sigma factor interacts with promoters in a manner similar to that of its homolog in Escherichia coli, sigma 70. These mutant derivatives of sigma A also provide a tool that may be useful for determining whether sigma A uses specific promoters in vivo. PMID- 1904430 TI - Development in Myxococcus xanthus involves differentiation into two cell types, peripheral rods and spores. AB - Myxococcus xanthus, a gram-negative bacterium, has a complex life cycle. In response to starvation, most cells in a population participate in the formation of multicellular aggregates (i.e., fruiting bodies) in which cells differentiate into spores. However, some cells do not enter aggregates. In this and the two accompanying reports, the biology and physiology of these nonaggregated cells is examined. A technique to separate aggregated cells from nonaggregated cells was developed; then differentiating cells at stages throughout the course of development were isolated. In this report we (i) describe peripheral rods, those cells which remain outside aggregates after aggregation has ceased in the rest of the population; (ii) document the occurrence of peripheral rods in several wild type strains; and (iii) characterize the expression of developmentally regulated genes in both aggregated and nonaggregated cells. These studies have shown that myxobacterial hemagglutinin, protein S (Tps), protein S1 (Ops), protein C, and several phosphatase activities are expressed in cell-type-specific patterns. These data demonstrate that peripheral rods constitute a cell type distinct from either vegetatively growing cells or spores. The description of a second, late developmental cell type (in addition to spores) opens an entirely new line of investigation in M. xanthus, i.e., the regulation of the differentiation of vegetatively growing cells into two cell types that differ significantly in biology, shape, and localization within the population. PMID- 1904431 TI - Analysis of Myxococcus xanthus cell types by two-dimensional polyacrylamide gel electrophoresis. AB - Myxococcus xanthus is a gram-negative, soil-dwelling bacterium that undergoes development in response to depletion of nutrients. Whereas most cells aggregate into multicellular mounds in which they differentiate into spores, 10 to 20% of the developing cells remain outside fruiting bodies as peripheral rods. We used two-dimensional polyacrylamide gel electrophoresis to analyze the global expression of polypeptides in cells taken from six stages in the life cycle: vegetatively growing cells, cells 15 h after the induction of development, peripheral rods, prespores (sonication-sensitive, aggregated cells), fruiting body spores (sonication-resistant, aggregated cells) 96 h after the induction of development, and glycerol-induced spores 15 h after induction. Seven hundred sixty-one discrete sample spots (SSPs) were identified among the six gels. Comparisons among the samples revealed that each sample had some unique SSPs, ranging from 0.3% of the 15-h developing cell SSPs to 17.9% of 96-h peripheral rod SSPs. Sixty-eight SSPs were ubiquitously distributed, but the relative amounts of these SSPs varied among the samples. Statistical analyses of the distribution and relative quantities of the SSPs indicate that, within a confidence level of greater than 99.99%, peripheral rods are significantly different from vegetatively growing cells, 15-h developing cells, prespores, fruiting-body spores, and glycerol-induced spores. In fact, among the six samples studied, only 15-h developing cells and glycerol-induced spores were similar to each other within a confidence level of P greater than or equal to 0.05. These results are consistent with the description of peripheral rods as a distinct developmental cell type. PMID- 1904432 TI - Behavior of peripheral rods and their role in the life cycle of Myxococcus xanthus. AB - Myxococcus xanthus is a gram-negative bacterium with a complex life cycle including a developmental phase in which cells aggregate and sporulate in response to starvation. In previous papers, we have described a heretofore unsuspected layer of complexity in the development of M. xanthus: vegetatively growing cells differentiate into two cell types during development. In addition to the differentiation of spores within fruiting bodies, a second cell type, peripheral rods, arises outside fruiting bodies. The pattern of expression of proteins in peripheral rods is different from that of either vegetatively growing cells or spores, and peripheral rods express a number of recognized developmental markers. In this report, we examine four aspects of the biology of peripheral rods: (i) the influence of nutrients on the proportion of peripheral rods in a population of developing cells, (ii) the capacity of peripheral rods to recapitulate development, (iii) the development of peripheral rods on conditioned medium, and (iv) the ability of peripheral rods to resume growth on low amounts of exogenously added nutrients. The results of these studies suggest that peripheral rods play a significant role in the life cycle of M. xanthus by allowing the exploitation of low amounts or transient influxes of nutrients without the investment of energy in spore germination. The differentiation of vegetatively growing cells into two cell types that differ significantly in biology, shape, and localization within the population has been incorporated into a model of the life cycle of M. xanthus. PMID- 1904433 TI - Identification and initial topological analysis of the Rickettsia prowazekii ATP/ADP translocase. AB - The Rickettsia prowazekii ATP/ADP translocase was identified by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis (PAGE) and immunoblot analysis using antibodies raised against a synthetic peptide corresponding in sequence to the carboxyl-terminal 17 amino acids of the carrier. Both the translocase of R. prowazekii and that expressed by Escherichia coli transformants containing the rickettsial gene had an apparent molecular mass of 36,500 Da by SDS-PAGE analysis, a mass considerably less than that deduced from the sequence of the gene. The SDS-solubilized translocase aggregated upon heating at 100 degrees C in the presence of disulfide bond-reducing agents. Similar concentrations of disulfide bond-reducing agents inhibited the exchange transport of adenine nucleotides by both R. prowazekii and translocase-expressing E. coli. These data suggested that an intramolecular disulfide bond in the translocase was essential for transport activity. The antipeptide antibodies used for identification of the translocase bound preferentially to inside-out membrane vesicles of translocase expressing E. coli relative to right-side-out spheroplasts, thus indicating that the carboxyl terminus of the carrier is located on the cytoplasmic side of the bacterial inner membrane. Protease studies were unable to localize the carboxyl terminus because of the resistance of this region of the native translocase to proteolytic cleavage. These data in conjunction with hydrophobicity analysis were used to construct an initial topological model of the translocase within the cell membrane. PMID- 1904434 TI - DNA sequences of three beta-1,4-endoglucanase genes from Thermomonospora fusca. AB - The DNA sequences of the Thermomonospora fusca genes encoding cellulases E2 and E5 and the N-terminal end of E4 were determined. Each sequence contains an identical 14-bp inverted repeat upstream of the initiation codon. There were no significant homologies between the coding regions of the three genes. The E2 gene is 73% identical to the celA gene from Microbispora bispora, but this was the only homology found with other cellulase genes. E2 belongs to a family of cellulases that includes celA from M. bispora, cenA from Cellulomonas fimi, casA from an alkalophilic Streptomyces strain, and cellobiohydrolase II from Trichoderma reesei. E4 shows 44% identity to an avocado cellulase, while E5 belongs to the Bacillus cellulase family. There were strong similarities between the amino acid sequences of the E2 and E5 cellulose binding domains, and these regions also showed homology with C. fimi and Pseudomonas fluorescens cellulose binding domains. PMID- 1904435 TI - Isolation of a coenzyme M-auxotrophic mutant and transformation by electroporation in Methanococcus voltae. AB - An auxotrophic mutant of Methanococcus voltae was isolated that required coenzyme M (CoM) for growth. With the mutant as a recipient, conditions were developed that allowed the introduction of wild-type CoM+ DNA into the mutant methanogen via electroporation. This method also allowed the rescue of both a histidine and purine auxotroph as well as the introduction of DNA determining resistance to the CoM analog 2-bromoethanesulfonic acid. Electroporation of the CoM(+)-determining DNA was 50- to 80-fold more efficient than natural transformation. PMID- 1904436 TI - Evolutionary relationships among eubacteria, cyanobacteria, and chloroplasts: evidence from the rpoC1 gene of Anabaena sp. strain PCC 7120. AB - RNA polymerases of cyanobacteria contain a novel core subunit, gamma, which is absent from the RNA polymerases of other eubacteria. The genes encoding the three largest subunits of RNA polymerase, including gamma, have been isolated from the cyanobacterium Anabaena sp. strain PCC 7120. The genes are linked in the order rpoB, rpoC1, rpoC2 and encode the beta, gamma, and beta' subunits, respectively. These genes are analogous to the rpoBC operon of Escherichia coli, but the functions of rpoC have been split in Anabaena between two genes, rpoC1 and rpoC2. The DNA sequence of the rpoC1 gene was determined and shows that the gamma subunit corresponds to the amino-terminal half of the E. coli beta' subunit. The gamma protein contains several conserved domains found in the largest subunits of all bacterial and eukaryotic RNA polymerases, including a potential zinc finger motif. The spliced rpoC1 gene from spinach chloroplast DNA was expressed in E. coli and shown to encode a protein immunologically related to Anabaena gamma. The similarities in the RNA polymerase gene products and gene organizations between cyanobacteria and chloroplasts support the cyanobacterial origin of chloroplasts and a divergent evolutionary pathway among eubacteria. PMID- 1904437 TI - The metR binding site in the Salmonella typhimurium metH gene: DNA sequence constraints on activation. AB - Transcription of the metH gene in Salmonella typhimurium and Escherichia coli is positively regulated by the metR gene product, a DNA binding protein. The interaction between the MetR activator protein and the S. typhimurium metH control region was investigated. In vitro gel mobility shift assays and DNase I protection assays established that the MetR protein binds to and protects a 24-bp sequence in the metH promoter region from DNase I attack. This region includes the proposed metR recognition sequence 5'-TGAANNNNNCTCA-3'. Single-base-pair changes were introduced into the proposed MetR recognition sequence within the promoter region of a metH-lacZ gene fusion by oligonucleotide-directed mutagenesis. Two classes of mutations were identified. In the first class, the mutations caused reduced activation of the metH-lacZ fusions that correlated with reduced MetR binding. In the second class, activation of the metH-lacZ fusion was reduced, yet there was no appreciable reduction in MetR binding, indicating that the presence of bound MetR is not sufficient for activation of metH-lacZ gene expression. These two classes of mutations in the DNA binding site are grouped spatially, suggesting that the proposed MetR recognition sequence can be divided into two functional domains, one for binding and the other for activation. PMID- 1904438 TI - Cloning and nucleotide sequence of the anaerobically regulated pepT gene of Salmonella typhimurium. AB - The anaerobically regulated pepT gene of Salmonella typhimurium has been cloned in pBR328. Strains carrying the pepT plasmid, pJG17, overproduce peptidase T by approximately 70-fold. The nucleotide sequence of a 2.5-kb region including pepT has been determined. The sequence codes for a protein of 44,855 Da, consistent with a molecular weight of approximately 46,000 for peptidase T (as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and gel filtration). The N-terminal amino acid sequence of peptidase T purified from a pJG17 containing strain matches that predicted by the nucleotide sequence. A plasmid carrying an anaerobically regulated pepT::lacZ transcriptional fusion contains only 165 bp 5' to the start of translation. This region contains a sequence highly homologous to that identified in Escherichia coli as the site of action of the FNR protein, a positive regulator of anaerobic gene expression. A region of the deduced amino acid sequence of peptidase T is similar to segments of Pseudomonas carboxypeptidase G2, the E. coli peptidase encoded by the iap gene, and E. coli peptidase D. PMID- 1904439 TI - Properties of the Bacillus subtilis chemotaxis protein CheF, a homolog of the Salmonella typhimurium flagellar protein FliJ. AB - The nucleotide sequence of Bacillus subtilis cheF was corrected. It encodes an 18 kDa protein that is homologous to FliJ, a protein required for formation of basal bodies in Escherichia coli and Salmonella typhimurium. Methanol release is abnormal in cheF mutants, suggesting that the morphology and functioning of the motor affects methanol formation. PMID- 1904441 TI - Acyl-acyl carrier protein specificity of UDP-GlcNAc acyltransferases from gram negative bacteria: relationship to lipid A structure. AB - Lipid A, the component of lipopolysaccharide that provides the membrane anchor of the core and O-antigen sugars, is known to contain characteristic R-3-hydroxy fatty acids bound to the 2,2' (N-linked) and 3,3' (O-linked) positions of the glucosamine disaccharide in different gram-negative bacteria. The studies reported here show that it is the acyl-acyl carrier protein specificities of the enzymes UDP-GlcNAc-O-acyltransferase and UDP-3-O-[(R)-3-hydroxyacyl]-GlcN-N acyltransferase that determine the nature of these fatty acids. PMID- 1904440 TI - DNA damage-inducible loci in Salmonella typhimurium. AB - lac operon fusions to DNA damage-inducible (din) loci were generated in Salmonella typhimurium LT2. Many of these din fusions were efficiently repressed by cloned Escherichia coli LexA, while others were not; all required RecA for induction. Several din fusions exhibited strong inducibility and will be useful in developing an SOS induction assay in S. typhimurium to detect genotoxins. PMID- 1904442 TI - Protein U, a late-developmental spore coat protein of Myxococcus xanthus, is a secretory protein. AB - Protein U is a spore coat protein produced at the late stage of development of Myxococcus xanthus. This protein was isolated from developmental cells, and its amino-terminal sequence was determined. On the basis of this sequence, the gene for protein U (pru) was cloned and its DNA sequence was determined, revealing an open reading frame of 179 codons. The product from this open reading frame has a typical signal peptide of 25 amino acid residues at the amino terminal end, followed by protein U of 154 residues. This result indicates that protein U is produced as a secretory precursor, pro-protein U, which is then secreted across the membrane to assemble on the spore surface. This is in sharp contrast to protein S, a major spore coat protein produced early in development, which has no signal peptide, indicating that there are two distinct pathways for trafficking of spore coat proteins during the differentiation of M. xanthus. PMID- 1904443 TI - The tryptophan-specific permease gene, mtr, is differentially regulated by the tryptophan and tyrosine repressors in Escherichia coli K-12. AB - The regulation of transcription of the gene for the tryptophan-specific permease, mtr, was evaluated in several genetically marked Escherichia coli strains through the use of a single-copy lacZ reporter system. The expression of mtr was repressed 97-fold by tryptophan via the Trp repressor and induced 10-fold by phenylalanine or tyrosine via the Tyr repressor. By primer extension analysis two distinct mtr transcripts and their corresponding promoters were identified. One transcript was induced by the Tyr repressor. The tryptophan-dependent interaction of Trp repressor with an operator target within the mtr promoter was demonstrated by means of a restriction endonuclease protection assay. PMID- 1904444 TI - Inhibition of autophagic-lysosomal delivery and autophagic lactolysis by asparagine. AB - Overall autophagy was measured in isolated hepatocytes as the sequestration and lysosomal hydrolysis of electroinjected [14C]lactose, using HPLC to separate the degradation product [14C]glucose from undegraded lactose. In addition, the sequestration step was measured separately as the transfer from cytosol to sedimentable cell structures of electroinjected [3H]raffinose or endogenous lactate dehydrogenase (LDH; in the presence of leupeptin to inhibit lysosomal proteolysis). Inhibitor effects at postsequestrational steps could be detected as the accumulation of autophaged lactose (which otherwise is degraded intralysosomally), or of LDH in the absence of leupeptin. Asparagine, previously shown to inhibit autophagic but not endocytic protein breakdown, strongly suppressed the autophagic hydrolysis of electroinjected lactose. Vinblastine, which inhibits both types of degradation, likewise suppressed lactose hydrolysis. Asparagine had little or no effect on sequestration, but caused an accumulation of autophaged LDH and lactose, indicating inhibition at a postsequestrational step. Neither asparagine nor vinblastine affected the degradation of intralysosomal lactose preaccumulated in the presence of the reversible lysosome inhibitor propylamine. However, if lactose was preaccumulated in the presence of asparagine, both asparagine and vinblastine suppressed its subsequent degradation. The data thus indicate that autophagic-lysosomal delivery, i.e., the transfer of autophaged material from prelysosomal vacuoles to lysosomes, is inhibited selectively by asparagine and non-selectively by vinblastine. PMID- 1904445 TI - Accumulation of talin in nodes at the edge of the lamellipodium and separate incorporation into adhesion plaques at focal contacts in fibroblasts. AB - The focal contact forms beneath F-actin-rich ribs, or cytoplasmic precursors, present in the lamellipodia of fibroblasts. The basal part of the precursor is retained at the contact as the initial adhesion plaque. We have examined the distribution of talin in the lamellipodia and adhesion plaques of chicken embryo fibroblasts relative to the process of focal contact formation. Motility of single cells was recorded with differential interference contrast or interference reflection microscopy before fixation and fluorescent staining for talin, F actin, and vinculin. Talin is present along the extreme edge of the lamellipodium, where it is further concentrated into a series of nodes. The nodes of talin are present at the tips of both larger and finer F-actin-rich ribs and at small structural nodes at the edge of the lamellipodium. We suggest that the talin in the nodes functions, via a cross-linking activity, in the convergence of actin filaments at the membrane during development of the ribs. Talin accumulates de novo in the adhesion plaque, independent of that at the tip of the precursor, in response to contact with the substrate. This second accumulation of talin at the focal contact starts before vinculin, consistent with a sequential binding of talin at the membrane and of vinculin to talin. The results imply that talin functions independently at two steps during formation of the focal contact: the development of the F-actin-rich precursor of the contact; and development of the contact-associated adhesion plaque, both involving organization of F-actin at the membrane. PMID- 1904446 TI - Integration site-dependent expression of a transgene reveals specialized features of cells associated with neuromuscular junctions. AB - After skeletal muscle is denervated, fibroblasts near neuromuscular junctions proliferate more than fibroblasts distant from synaptic sites, and they accumulate adhesive molecules such as tenascin (Gatchalian, C. L., M. Schachner, and J. R. Sanes. 1989. J. Cell Biol. 108:1873-1890). This response could reflect signals that arise perisynaptically after denervation, preexisting differences between perisynaptic and extrasynaptic fibroblasts, or both. Here, we describe a line of transgenic mice in which patterns of transgene expression provide direct evidence for differences between perisynaptic and extrasynaptic fibroblasts in normal muscle. Transgenic mice were generated using regulatory elements from a major histocompatibility complex (MHC) class I gene linked to the Escherichia coli beta-galactosidase (lacZ) gene. Expression of lacZ was detected histochemically. In each of eight lines, lacZ was detected in different subsets of cells, none of which included lymphocytes. In contrast, endogenous MHC is expressed in most tissues and at high levels in lymphocytes. Thus, the MHC gene sequences appeared inactive in the transgene, and lacZ expression was apparently controlled by genomic regulatory elements that were specific for the insertion site. In one line, cells close to the neuromuscular junction were lacZ positive in embryonic and young postnatal mice. Electron microscopy identified these cells as fibroblasts and Schwann cells associated with motor nerve terminals, as well as endoneurial fibroblasts, perineurial cells, and Schwann cells in the distal branches of motor nerves. No intramuscular cells greater than 200 microns from synaptic sites were lacZ positive. These results indicate that there are molecular differences between perisynaptic and extrasynaptic fibroblasts even in normal muscle and that diverse perisynaptic cell types share a specific pattern of gene expression. PMID- 1904447 TI - Purification of a hybrid plasminogen activator protein. AB - Recombinant DNA technology has been employed to produce a hybrid gene in which the kringle and serine protease domains of tissue plasminogen activator are linked to the heavy-chain Fd region of a fibrin-specific antibody. The hybrid gene is co-expressed with antibody light chains. This communication describes a purification procedure for the hybrid protein, involving affinity and ion exchange chromatography. The purified hybrid protein has been used in vivo and in vitro clot lysis experiments and has been shown to be effective at clot dissolution. PMID- 1904448 TI - Affinity purification of plasminogen by radial-flow affinity chromatography. AB - A method for the purification of plasminogen using immobilized L-lysine on a membrane, the whole system being constructed in a radial flow cartridge, is described. Human plasma was applied to the cartridge at 20 ml/min. The results showed that under the chromatographic conditions chosen, in a single pass, greater than 85% recovery of plasminogen was attained with a 110-fold increase in specific activity. PMID- 1904449 TI - Interleukin-6 secreting human pituitary adenomas in vitro. AB - Interleukin-6 was found to be secreted from seven out of ten human pituitary tumours cultured in vitro. These tumours included prolactin-secreting, growth hormone-secreting and clinically non-functioning adenomas. The amount of Interleukin-6 secreted was variable from 58 to 10,000 units per ml. in medium removed after a four-day incubation under basal conditions. Four tumours secreted IL-6 in excess of 500U/ml, three of which were clinically non-functioning, but each secreted follicle stimulating hormone in vitro. This is the first report of a cytokine growth factor being released basally by human pituitary tumours. PMID- 1904450 TI - Amplification of pulsatile LH secretion by exogenous melatonin in women. AB - The effect of melatonin on pulsatile LH secretion was investigated in early follicular phase women (days 2-5). During two consecutive days, at 0800 hrs., subjects received placebo or oral melatonin in a random double-blind fashion. Two doses of melatonin were used; 100 mg single dose (N = 6) or 2.5 mg in three divided doses (N = 5), (1 mg at 0800 hrs., 0.75 mg at 1000 and 1200 hrs.). Blood samples were collected every 10 minutes, between 0900-1700 hrs. Compared with placebo, melatonin administration augmented LH pulse amplitude (p less than 0.01) without changing LH pulse frequency. The integrated LH secretion was significantly increased (p less than 0.01) after melatonin, independent of doses administered. Serum FSH and ovarian steroids were not altered. It is concluded that exogenous melatonin enhances LH pulse amplitude in women, without modifying FSH and ovarian steroid levels. PMID- 1904451 TI - Slowing of pulsatile luteinizing hormone secretion in men after forty-eight hours of fasting. AB - To determine whether short periods of fasting can suppress the activity of the reproductive axis in normal healthy men, eight men were studied on a fed day and again after 48 h of fasting. Subjects were between 20-32 yr of age and ranged from 84-119% of normal body weight. Blood samples were collected on day 1 (a fed day) and day 3 (after 48 h of fasting) at 15-min intervals from 0800-1600 h through indwelling venous catheters. Fasting for 48 h resulted in a significant decrease in mean LH, FSH, and testosterone concentrations. The mean LH concentration decreased from 2.94 +/- 0.59 IU/L on the fed day to 1.07 +/- 0.14 IU/L after 48 h of fasting, and there was an accompanying decrease in LH pulse frequency (from 5.13 +/- 0.29 to 2.63 +/- 0.62 pulses/8 h) and mean baseline LH concentration (from 1.83 +/- 0.52 to 0.51 +/- 0.07 IU/L), but no significant decrease in LH pulse amplitude. In a second study, blood samples were collected from five subjects who were allowed to eat normally between days 1 and 3; these individuals showed no difference in LH secretion. To begin to examine the possibility that an activation of the hypothalamic-pituitary-adrenal axis leads to the suppression of reproductive hormone levels that occurred after 48 h of fasting, cortisol levels were measured in all plasma samples. There was no significant difference in mean cortisol concentrations on fed vs. fasted days or when cortisol concentrations were examined as hourly means across the 2 days. These results indicate that activity of the reproductive axis can be suppressed in normal healthy men by 48 h of fasting. It appears unlikely that activation of the adrenal axis is the cause of this suppression of reproductive axis activity. PMID- 1904452 TI - Depot leuprolide acetate dosage for sexual precocity. AB - Twenty-one children with early puberty have been evaluated to determine adequate dosage of depot leuprolide acetate. The minimal dosage of depot leuprolide acetate required, using intervals of 1.5 mg or less when given every 28 days, was determined. This dosage, as determined by suppression of gonadotropin responses to GnRH stimulation, was 4.14 +/- 1.33 mg (mean +/- SD) and 0.15 +/- 0.07 mg/kg.28 days. The dosage correlates with bone age and pubertal stage and is larger among patients with more advanced puberty. Five patients required a larger dosage from 5-10 months after initial suppression. Therefore, to monitor suppression, GnRH testing should be repeated at least at 6-month intervals. Samples 20 and 40 min after GnRH stimulation are sufficient to indicate adequacy of treatment, so an abbreviated test could be used. PMID- 1904453 TI - Stimulation by human chorionic gonadotropin of prostaglandin synthesis by early human placental tissue. AB - Successful establishment of pregnancy is dependent on inhibition of clotting and suppression of the maternal immune response at the feto-maternal interface. Early human placental production of prostacyclin (PGI2) and prostaglandin E2 (PGE2) may be important in this process. To examine the possible role of these PGs, we studied PGE and 6-keto-PGF1 alpha (stable metabolite of PGI2) synthesis in human placental (9-17 weeks gestation) organ cultures, and monolayer cultures of purified trophoblasts. PGE2 appeared to be the major protanoid formed. Other arachidonic acid metabolites identified in placental organ culture were 6-keto PGF1 alpha, thromboxane B2, PGF2 alpha, leukotriene B4, 5(S) hydroxyeicosatetraenoic acid (5-HETE), 12-HETE, and 15-HETE. The synthesis of PGE and 6-keto-PGF1 alpha altered with gestation and was maximal in the younger placentas. Arachidonic acid (33 microM) stimulated and indomethacin (28 microM) inhibited PG production. hCG, including physiological concentrations, stimulated PGE and 6-keto-PGF1 alpha synthesis in placental organ cultures. This effect was most striking in the 9-12 week placentas, compared to 15-17 week placentas. A similar hCG-induced stimulation of PGE production occurred in monolayer cultures of trophoblasts. The addition of TSH, FSH, and LH indicated that this effect was specific for hCG. These data suggest that hCG may have a biological role in the regulation of PG synthesis in early human placenta. PMID- 1904454 TI - Hypothalamic-pituitary dysfunction in growth hormone-deficient patients with pituitary abnormalities. AB - Hypothalamic-pituitary function was studied in 45 patients with idiopathic GH deficiency (GHD), 33 of whom had pituitary abnormalities on magnetic resonance imaging: pituitary hypoplasia, undescended stalk and ectopia of the posterior lobe in 8 patients with isolated GHD (IGHD) (group I) and in 12 patients with multiple pituitary hormone deficiency (MPHD) (group II); isolated pituitary hypoplasia in 13 patients with IGHD (group III); no evidence of pituitary abnormalities in the remaining 12 patients with IGHD (group IV). Sellar and pituitary volumes were significantly lower in groups I, II, and III than in group IV (P less than 0.001). No significant differences were observed between group I and group II in the GH response to GHRH1-44 expressed both as peak serum GH and area under the curve. Mean GH peak in group III and IV was significantly higher than that in group I (P less than 0.005) and II (P less than 0.001), as were the mean AUC (P less than 0.005), suggesting hypothalamic defect. Delayed peak serum TSH after TRH was found in all patients of group II, and overt hypothyroidism in 11 of them. Furthermore, basal hyperprolactinemia was present in 6 patients and adrenal insufficiency in 7 cases of group II. Finally, a reduced response of FSH to GnRH was observed in all these patients (P less than 0.005 vs. each of the other groups), and clinical hypogonadism was present in all of them. We suggest that: 1) A high incidence of pituitary abnormalities seems to be present in idiopathic GHD patients; 2) Pituitary hormone deficiencies are more dependent on the type of the hypothalamic-pituitary abnormality than on the size of the pituitary per se: the association of pituitary hypoplasia, undescended stalk and ectopia of the posterior lobe should possibly be considered a distinct entity reflecting an early abnormality in hypothalamic development; 3) The majority of patients with IGHD or MPHD probably have a primary hypothalamic releasing hormone deficiency even if pituitary hypoplasia is associated; 4) Magnetic resonance imaging may have a role in the diagnosis and prognosis of patients with GHD through differentiation between patients who are at risk for developing MPHD vs. those who are candidates for having a persistently isolated GHD. PMID- 1904455 TI - Red cell aplasia in myelodysplastic syndrome. AB - Six cases of red cell aplasia occurring in patients with myelodysplastic syndromes (MDS) showed a diversity of clinical course and prognosis. In some patients red cell aplasia may have represented an evolution of MDS while in others autoimmune destruction of erythoblasts may have been the mechanism. A proliferative phase is seen in many of these patients, the clinical importance of which is uncertain. PMID- 1904456 TI - Multipoint microbiological assay for detecting beta-lactamase. AB - A multipoint microbiological assay for determining beta-lactamase production by clinical isolates of bacteria was evaluated. With strains of Haemophilus influenzae, Neisseria gonorrhoeae, and Branhamella catarrhalis there was excellent correlation between results obtained using this method and those obtained using the chromogenic cephalosporin reference method. The multipoint method is an inexpensive yet reliable adjunct to conventional susceptibility testing methods. PMID- 1904458 TI - Managing patients undergoing radiation. PMID- 1904457 TI - Evaluation of two fluorogenic assays for identification of Streptococcus species isolated from bovine mammary glands. AB - Liquid and agar assays that utilized 4-methylumbelliferyl-conjugated beta-D glucuronide, beta-D-galactoside, or N-acetyl-beta-D-glucosaminide, and agglutination by Dolichos biflorus lectin were evaluated for identification of Streptococcus species isolated from bovine mammary glands. A greater number of Streptococcus uberis isolates were negative for N-acetyl-beta-D-glucosaminidase by the liquid assay compared with the agar assay. Enzyme profiles for Streptococcus dysgalactiae were similar by both assays. Streptococcus dysgalactiae was the only species that agglutinated when mixed with lectin from D. biflorus. Most Streptococcus agalactiae isolates were positive for beta-D glucuronidase and beta-D-galactosidase by both assays. Two Streptococcus equinus strains had negative enzyme profiles by the liquid assay; however, both strains had enzyme profiles consistent for S. equinus by the agar method. Incorporation of 4-methylumbelliferyl-conjugated substrates into trypticase soy agar did not appear to alter agar characteristics and eliminated aliquoting substrates and inoculating tubes. More than one enzyme profile was produced per Streptococcus species or serogroup by both methods. However, some profiles were similar between species, which hindered accurate identification of Streptococcus species. PMID- 1904459 TI - Evidence suggesting involvement of interleukin-4 (IL-4) production in spontaneous in vitro IgE synthesis in patients with atopic dermatitis. AB - To investigate the regulatory role of interleukin-4 (IL-4) and interferon-gamma (INF-gamma) and their involvement in the abnormality of IgE synthesis in patients with atopic dermatitis (AD), we studied the effect of recombinant human IL-4 and INF-gamma, as well as blocking antibodies (Abs) to these lymphokines on spontaneous IgE synthesis by peripheral blood lymphocytes (PBLs) from patients with AD and from healthy control subjects. PBLs from patients with AD demonstrated elevated spontaneous IgE production that was not stimulated further by the addition of recombinant IL-4, whereas for the healthy control subjects, recombinant IL-4 increased spontaneous IgE production by PBLs. INF-gamma that has been previously demonstrated to antagonize the effect of IL-4 on IgE synthesis, decreased IgE production of patients with AD. Addition of Abs to INF-gamma did not change spontaneous IgE production for patients with AD or for healthy control subjects. Together with our observation that IL-4 Abs lowered the high spontaneous IgE production by PBLs from patients with AD, these results suggest that in AD, IL-4 production by lymphocytes, together with a lack of INF-gamma production, is at least partially responsible for the increased spontaneous IgE production. PMID- 1904460 TI - Infant-onset progressive myoclonus epilepsy. AB - We report the clinical, electroencephalographic, neurophysiologic, and neuroimaging findings in eight children with infant-onset progressive myoclonus epilepsy, all of whom had muscle biopsies performed as as part of the diagnostic evaluation. Each child had myoclonic seizures, generalized tonic-clonic seizures, and neurologic regression or marked developmental delay. Four children died before 3 years of age. Electroencephalograms in seven children showed an abnormally slow background with bilateral multifocal paroxysmal discharges but no burst suppression pattern or photoparoxysmal response. Muscle biopsy specimens were submitted for histopathology and respiratory-chain enzyme studies. Nonspecific abnormalities on light microscopy or electron microscopy were found in seven samples, including increased subsarcolemmal deposits of mitochondria or morphologic mitochondrial changes, but no ragged-red fibers were seen. Respiratory-chain enzyme studies were performed on five samples and in three children (all of whom had a history of elevated lactate in serum or cerebrospinal fluid), there were low levels of rotenone-sensitive reduced nicotinamide adenine dinucleotide (NADH) cytochrome c reductase characteristic of a defect in the complex I part of the respiratory-chain pathway. This study has shown that infant onset progressive myoclonus epilepsy can be distinguished from other myoclonic epilepsy syndromes of infancy by clinical and electrographic features. Furthermore, respiratory-chain enzyme defects are a relatively common cause of infant-onset progressive myoclonus epilepsy. The absence of ragged-red fibers on muscle histopathology does not preclude a mitochondrial enzyme abnormality. PMID- 1904461 TI - The effect of sleep on intracranial hemodynamics: a transcranial Doppler study. AB - The effect of sleep on intracranial blood flow velocities has not been reported in children or adults, even though blood flow velocities are evaluated for clinical purposes during both sleep and wakefulness. We report the effect of sleep on intracranial blood flow velocities of 11 healthy individuals (five children and six adults) who were monitored by polysomnography and transcranial Doppler sonography (TCD). Thirty-three TCDs were obtained on middle cerebral arteries. Before sleep, during non-rapid-eye-movement sleep, and after sleep, measurements of systolic, end diastolic, and mean flow velocities were obtained by TCD. Pulse oximetry and end tidal carbon dioxide were monitored during each 8 hour polysomnogram. The before-sleep blood flow velocity values were compared to sleep and after-sleep values in children and adults separately using ANOVA. A significant decrease in the blood flow velocities was noted during sleep compared to before-sleep values in both children (P less than .05) and adults (P less than .01). The blood flow velocities after sleep were also decreased compared to before-sleep values. This study shows that sleep reduces blood flow velocities in both children and adults. A decrease in blood flow velocities during normal sleep should be taken into account when interpreting TCDs in patients. PMID- 1904462 TI - The elbow. PMID- 1904463 TI - Systematic fractionation of serum antibodies using multiple antigen homologous peptides as affinity ligands. AB - The fractionation of polyclonal antibodies on multiple peptide ligands is described. The method is an application of a procedure for the synthesis of large numbers of peptides on individual polyethylene pins (Geysen et al., 1987). In this application, each pin-bound peptide is used as an affinity support. Antibodies bound to the peptides are then eluted, using buffers of either high or low pH. Each eluted antibody is then tested for specific binding to peptides or proteins, using ELISA procedures. A rabbit antiserum raised to gonococcal pilin was fractionated on a complete set of octapeptides homologous with the sequence of the pilin protein. Antibodies eluted from some of the peptides bound to pilin in solution. In a second example three hyperimmune sera raised to three different potyviruses were fractionated on their respective homologous peptide sequences. Testing the eluted antibodies on the three virus coat proteins revealed peptides which bound cross-reacting antibodies. Thus the method can be used to confirm direct peptide binding evidence for sequential epitopes. These peptides can then be used in affinity chromatography to increase the specificity of polyclonal sera. This can be achieved either by elution of the specific antibody from the peptide or by removal of cross-reacting antibodies from the whole serum by absorption on peptide. PMID- 1904466 TI - Sensitive one-step enzyme immunoassay for HIV-1 p24 antigen in human blood specimens and cell culture supernatants. AB - An enzyme immunoassay (EIA) with a single incubation step has been developed to detect the HIV-1 major core polypeptide p24 in human blood specimens and in cell culture supernatants. In this assay, the solid phase is coated with monoclonal antibodies to p24, and the specimen is incubated simultaneously with peroxidase labelled polyclonal anti-HIV(Fab'). If HIV-1 p24 antigen is present in a specimen it will form a sandwich complex with the capture and tracer antibodies during the incubation step. The sensitivity of the assay for p24 antigen, 20 pg/ml, was equal to that of two commercial HIV antigen detection EIAs, when human blood specimens and virus isolation cell culture supernatants were analyzed. However, the assay described is simpler to perform than those previously reported, since only one incubation step is needed. Moreover this assay minimizes the handling of material containing potentially infectious HIV. PMID- 1904465 TI - A convenient human whole blood culture system for studying the regulation of tumour necrosis factor release by bacterial lipopolysaccharide. AB - Bacterial lipopolysaccharide (LPS, endotoxin) induces a dose-dependent release of TNF in whole human blood which has been diluted five-fold. It is modulated by interferon-gamma, prostaglandin E2 and indomethacin in the same manner as observed with tumour necrosis factor (TNF) release from human monocyte/macrophage cells cultured in vitro. The whole blood culture system (WBCS) can provide up to 250 samples from 10 ml of venous blood and enables an individual blood to be assessed in terms of TNF inducibility and its modulation by other biological agents. The whole blood culture system was used to demonstrate the individual variation between blood donors. The results demonstrated that the information provided by induced cytokine release and its regulation in the ex vivo system would be a valuable addition to that obtained from in vitro methods. PMID- 1904464 TI - Evaluation of a test system for measuring cytokine production in human whole blood cell cultures. AB - A simple and reproducible method is described for the measurement of mitogen induced cytokine production in cultures of both human peripheral blood mononuclear cells (PBMC) and whole blood. In the culture supernatants the cytokines interleukin-1 alpha (IL-1 alpha), interleukin-2 (IL-2), interferon gamma (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) were determined by a rapid and sensitive immunoassay using various monoclonal and polyclonal antibodies. Comparing the PBMC cultures with the whole blood system a good correlation was obtained if the cell number was taken into account. In the post induction supernatants the cytokine values were found to follow typical kinetic curves. The protocol was evaluated by screening 60 cancer patients with primary disease and 60 healthy controls. A markedly reduced secretion of IFN-gamma and IL 1 alpha was found in the cancer patients compared to controls, although leukocyte and lymphocyte counts were almost identical in both groups. PMID- 1904467 TI - Effects of oxygen tension on the growth and pigmentation of normal human melanocytes. AB - The effects of oxygen tension on human melanocyte growth, tyrosinase activity, and melanin production were assessed. Melanocytes, seeded at 10(4) cells/cm2, were grown in modified Eagle's medium (MEM) with 5% fetal bovine serum (FBS) and 10 ng/ml 12-O-tetradecanoyl-phorbol-13-acetate (TPA). Flasks were equilibrated with gas mixtures containing 5% CO2 and various partial pressures of oxygen (PO2 7-620 mm Hg) and kept in incubators, which were electronically maintained at the desired oxygen tensions. Melanocytes grew best at PO2 from 6-34 mm Hg. Growth was reduced by 30% at PO2 142 mm Hg, and even more at O2 tensions greater than 230 mm Hg. A PO2 of 603 mm Hg was cytotoxic. Tyrosinase activity (assayed by the method of Pomerantz) was 300 microU/mg protein at PO2 7-34 mm Hg. At PO2 235 and 355 mm Hg tyrosinase activity decreased to about 100 microU/mg protein. The apparent Km for tyrosine was unchanged in melanocytes cultured at all experimental oxygen tensions. The Vmax, however, was decreased at the higher oxygen tensions (PO2 235 mm Hg). At PO2 6-135 mm Hg the melanin content was proportional to tyrosinase activity. At cytostatic oxygen tensions (PO2 235 and 355 mm Hg) the intracellular melanin content increased somewhat, although tyrosinase activity was decreased. Low oxygen tension is favorable for both melanocyte proliferation and tyrosinase activity. PMID- 1904468 TI - The influence of skin structure on permeability: an intersite and interspecies comparison with hydrophilic penetrants. AB - For reasons that are unclear, skin from various body sites has different permeability properties. We have used hydrophilic penetrants (water, ethanol, mannitol, and paraquat) to study the in vitro permeability of skin from marmoset (eight body sites), man, and rat. Skin structure (stratum corneum thickness and number of cell layers; epidermal and dermal thickness; number and area of hair follicle openings per mm2) was compared with permeability. There was no apparent relationship between skin structure and permeability to the most rapid penetrants, water and ethanol. Follicle area opening was the structural feature that varied most between species and between body sites. Different marmoset body sites showed a threefold range in follicle area but this did not appear to influence the absorption rates of the test penetrants. However, among the species there was an 80-times range in follicle area, which correlated with the observed differences in rate of mannitol and paraquat absorption. Thus, permeability could be related to inter-species differences in skin structure, but only with the relatively slowly absorbed test penetrants, mannitol and paraquat. PMID- 1904469 TI - Interleukin-1-like activity in normal rat skin after in vivo treatment with interferon-gamma. AB - The influence of interferon-gamma (IFN-gamma) on immune responses is still ambiguous. We have investigated whether IFN-gamma influences the constitutive interleukin-1 (IL-1)-like activity in normal rat skin because IL-1 is a regulatory cytokine in immune responses. Rats were injected intradermally into both ears with different doses of rat recombinant IFN-gamma (10(3)-10(5) U), and control animals were given phosphate-buffered saline (PBS). The animals were killed at different times and the ears were cut off at the bases. The biologic activity of the IFN-gamma was verified by immunohistochemistry on injected ears, showing a time- and dose-dependent induction of major histocompatibility complex class II antigens on the keratinocytes. Aqueous extracts of homogenized ear skin were tested for IL-1-like activity in a mouse thymocyte bioassay. No major effects of IFN-gamma on the constitutive IL-1-like activity in the rat skin were found; at 6 h there was a slight reduction and at 72 h an increase in IL-1 bioactivity in extracts from IFN-gamma (10(5) U)-injected animals compared with PBS-treated controls (p less than 0.05). We conclude that the regulation of immune responses in the rat skin by IFN-gamma is less likely to be mediated via changes in the IL-1-like activity. PMID- 1904470 TI - Bullous pemphigoid antigens: extraction and degradation of antigens during epidermal preparation. AB - Although two groups of bullous pemphigoid antigens have been well characterized, different research groups have shown strikingly different prevalence rates of antibodies to these antigens in their patients. Potential explanations for this phenomena include a patient population that has different prevalence of antibodies, or that the antigen preparations used by the different groups contain different relative amounts of these antigens. We have compared the relative concentration of the different bullous pemphigoid antigens in epidermal extract preparations made by three different procedures commonly used to separate dermis from epidermis: NaCl, ethylenediaminetetraacetic acid (EDTA), and heat. We have found that the amount of the 180-kD antigen present in extracts is dependent on the techniques involved in separation of the epidermis from dermis. NaCl- and EDTA-separation procedures result in partial proteolysis of the 180-kD antigen to smaller forms, including major brands at 160 kD and 97 kD in the EDTA preparation. Fragments of the 180-kD antigen are present in both the separation and wash fluids, associated with a significant reduction of the 180-kD form in the extract of the NaCl-separated skin. We conclude that the native molecular weight of the previously described minor bullous pemphigoid antigen is 180 kD, and that the apparent difference in patient reaction to the 180-kD antigen may be due to different preparations of the antigen rather than underlying differences in seropositivity in the patient population. PMID- 1904471 TI - [Endogenous arginine-specific ADP-ribosyltransferases and their target proteins]. PMID- 1904472 TI - [A case of granulosa cell tumor with unusual histologic features]. PMID- 1904474 TI - Biophysical and biochemical properties of an unusual birnavirus pathogenic for rotifers. AB - A cytoplasmic dsRNA virus, rotifer birnavirus (RBV), has recently been isolated from the rotifer Brachionus plicatilis and is associated with a high mortality rate. Histologically, the viral lesions consist of characteristic inclusions, particularly amorphous dense bodies containing occluded particles. Purified virions are about 59 nm in diameter, single-shelled and display four capsomers per edge. The purified virions have a buoyant density of 1.290 (full particles) and 1.250 (empty particles) in CsCl gradients. Four major structural polypeptides of MrS 60K, 52K, 33K and 27K were detected by SDS-PAGE. The genome is composed of two linear segments of dsRNA with MrS of 2.45 x 10(6) and 2.31 x 10(6); additionally, small circular ssRNA molecules were detected by electrophoresis in overloaded agarose gels, but their significance is currently unknown. Except for this last feature and the structural instability of purified virions under freeze storage, all the other biochemical and biophysical characters indicate that RBV is a member of the Birnaviridae family with, for the moment, a unique position in this group. PMID- 1904473 TI - Amino acids regulate kidney cell protein breakdown. AB - Amino acids inhibit breakdown of long-lived intracellular proteins in some but not all tissues studied. Because no information is available relating to the effect of amino acids on kidney cell proteolysis, this study was conducted with cultured proximal-like opossum kidney (OK) cells and primary cultured rabbit proximal tubular cells in which long-lived cell proteins were labeled with carbon 14-labeled valine. These cultured cells were acutely deprived of amino acids; this was followed by a 57% to 66% increase in the proteolytic rate in OK cells and a 22% rate increase in the rabbit kidney cells. In cultured OK cells incubated in serum-free minimal essential medium containing 13 amino acids, proteolysis averaged 4.62% +/- 0.28%/2 hr and increased to 7.66% +/- 0.38%/2 hr when amino acids were deleted. Each amino acid was then added alone. Leucine, phenylalanine, and lysine had significant effects in inhibiting the deprivation response by 40%, 26%, and 22%, respectively. Leucine appears to inhibit proteolysis directly and not through its metabolites, since alpha ketoisocaproate, the leucine transamination product, was without effect. Similarly, failure of tyrosine to inhibit proteolysis suggests a direct phenylalanine action. When leucine, phenylalanine, and lysine were simultaneously deleted from the incubation medium, the increase in proteolysis corresponded to 56% of the response after deletion of all amino acids. Thus to maximally affect proteolysis, amino acids, which on their own have little effect on protein breakdown, also appear to play a role. From this study we conclude that amino acids seem to play an important and direct role in the regulation of kidney epithelial cell protein breakdown. PMID- 1904475 TI - Auranticins A and B: two new depsidones from a mangrove isolate of the fungus Preussia aurantiaca. AB - Auranticins A and B, two new antimicrobial depsidones, have been obtained from a mangrove isolate of the fungus Preussia aurantiaca. The structures were determined through analysis of selective INEPT, decoupling, COSY, and NOESY experiments. PMID- 1904476 TI - Diterpenes from the Pohnpeian marine sponge Chelonaplysilla sp. AB - Nine diterpenes have been isolated from the marine sponge Chelonaplysilla sp. collected in Pohnpei, Federated States of Micronesia. These include the known diterpenes 1-bromo-8-ketoambliol A acetate, dendrillolide A, dendrillolide D, norrisolide, 12-desacetoxyshahamin C, and aplyviolene. Three novel rearranged spongian diterpenes, chelonaplysins A, B, and C, were identified by interpretation of spectral data and chemical correlation with known compounds. Aplyviolene, chelonaplysin B, and chelonaplysin C exhibited antimicrobial activity against the bacterium Bacillus subtilis. The secondary metabolite composition of this collection of Chelonaplysilla sp. is compared to the composition previously reported for samples from Palau. PMID- 1904477 TI - Long-term follow-up and prognostic factor analysis in advanced ovarian carcinoma: the Gynecologic Oncology Group experience. AB - Long-term follow-up was obtained on 726 women with advanced ovarian carcinoma (suboptimal stage III and stage IV) who had received primary chemotherapy on two Gynecologic Oncology Group (GOG) protocols between 1976 and 1982. The first study compared melphalan alone versus melphalan plus hexamethylmelamine versus cyclophosphamide plus doxorubicin (CA). The second study evaluated the same CA regimen with or without cisplatin. Eligibility for the two studies was the same. At last contact, 76 patients were alive. In a multivariate analysis, cell type other than clear cell or mucinous, cisplatin-based treatment, good performance status, younger age, lower stage, clinically nonmeasurable disease, smaller residual tumor volume, and absence of ascites were favorable characteristics for overall survival (P less than .05). Second-look laparotomy was negative significantly more often among those with endometrioid tumors; there were no negative second-look laparotomies among those with mucinous or clear cell tumors. There were 30 patients with suboptimal stage III disease who had a negative second-look laparotomy; 18 (60%) have experienced recurrence, and 13 (43%) have died. Although cisplatin treatment was beneficial, new treatments are clearly needed. PMID- 1904478 TI - Olfactory bulb granule cell aggregates: morphological evidence for interperikaryal electrotonic coupling via gap junctions. AB - Anaxonic interneurons of the granule cell type in the mammalian main olfactory bulb (MOB) are characterized by prominent membrane specializations, which include reciprocal, interdendritic chemical and electrical synapses; however, the latter are thought to be restricted to the external plexiform layer (EPL) and connect granule-mitral- and granule-tufted-cell dendrites (Landis et al., 1974). The present study focuses on interperikaryal membrane specializations between tangentially oriented aggregates of granule microneurons in the lamina granularis interna (IGL). Both infraprimate (Rattus norvegicus, Gerbillus perpallidus) and primate species (Callithrix jacchus) were studied using the following methods: (1) transmission electron microscopy (TEM), (2) freeze-fracture analysis, (3) light and TEM immunohistochemistry using affinity-purified antibodies directed against the connexin-32 or connexin-43 carboxy tail fragment of the gap-junction protein (GJP), and (4) intracellular Lucifer yellow injections in fixed tissue (LYF technique). Freeze-fracture replicas of the MOB-IGL showed that adjacent granule cell perikarya have numerous particle aggregates on the cytoplasmic membrane; in terms of their structure and arrangement, such particles are characteristic of gap junctions. The existence of junctional membranes was substantiated by application of antibodies against GJP demonstrating punctate immunoreactivity, frequently confined to the interperikaryal plasmalemmae of granule cells in the IGL and their dendritic processes in the EPL. Upon TEM analysis, GJP-like immunoreactivity was additionally found in membranous organelles, including Golgi apparati and associated vesicular components. In order to test the permeability of identified membrane specializations, the LYF technique was used, which resulted in bright fluorescence of the perikaryal and dendritic components of the transsomatically injected neuron and staining of neighboring neurons with similar morphology. These findings imply that small molecules can diffuse across the interperikaryal membrane specializations. The existence of gap junctions between granule cell perikarya suggests that there is a significant, low-resistance electrical transmission between aggregated granule cells. This coupling might permit synchronization of neural discharge among small aggregates of these neurons. Gap junctions between granule cells may also serve signaling functions associated with the protracted period of granule cell development. PMID- 1904479 TI - The effect of tau antisense oligonucleotides on neurite formation of cultured cerebellar macroneurons. AB - Tau, a microtubule-associated protein (MAP) enriched in axons, may have a role in the generation and maintenance of an axonal morphology. Neurons from embryonic day 15 rat cerebellum in culture elaborate two morphologically distinct neurite populations--one with nontapering, elongated axonlike neurites and the other with tapered dendritelike neurites that branch frequently and are selectively stained with antibodies to MAP2. Tau antisense oligonucleotides were utilized in two ways: (1) continuous application of antisense every 24 hr for variable periods of time or (2) application of antisense that was delayed until neurite differentiation was underway. In both cases, 24 hr after the administration of the antisense, tau protein was not detected immunocytochemically. When the antisense was given continuously directly after plating, the neurites persisted as simple minor outgrowths. When antisense was added 72 hr after plating, axonlike neurites were lost, while the remaining neurites continued to grow and increase in complexity. We concluded that the initial establishment of an elongated axonlike neurite is a prerequisite for further neurite maturation; however, once the axon is established, the remaining neurites are able to grow independently and assume a tapered dendritelike appearance. PMID- 1904480 TI - The distribution of synapsin I and synaptophysin in hippocampal neurons developing in culture. AB - As a first step toward elucidating mechanisms involved in the sorting of synaptic vesicle proteins in neurons, we have used immunofluorescence microscopy to determine the distribution of two synaptic vesicle proteins, synapsin I and synaptophysin, in hippocampal neurons developing in culture. In mature cultures, synapsin I and synaptophysin immunoreactivity was concentrated in puncta that were restricted to sites where axons contacted neuronal cell bodies or dendrites. Electron-microscopic immunocytochemistry demonstrated that these puncta corresponded to vesicle-filled axonal varicosities that were exclusively presynaptic. At early stages of development, before cell-cell contact, both synapsin I and synaptophysin were preferentially localized in axons, where they were particularly concentrated in the distal axon and growth cone. In axons that did not contact other cells, immunostaining for these two proteins had a granular appearance, which persisted for at least 7 d, but focal accumulations of vesicles comparable to those seen at sites of synaptic contact were not observed. When neurons contacted one another, numerous puncta of synapsin I and synaptophysin formed within the first week in culture. Double-label immunofluorescence demonstrated that the two vesicle antigens were closely codistributed throughout these stages of development. These observations demonstrate that synaptic vesicle proteins assume a polarized distribution within nerve cells beginning early in development, as soon as the axon can be identified. In contrast, differences in microtubule polarity orientation that distinguish mature axons and dendrites, and that have been proposed to account for the selective sorting of some materials in nerve cells, first appear at a subsequent stage of development. The selective distribution of synaptic vesicle proteins to the axon occurs in isolated cells, independent of interactions with other cells. In contrast, the formation of large clusters of vesicles typical of presynaptic specializations requires contact with an appropriate postsynaptic target. Thus, in cultured hippocampal neurons, the localization of synaptic vesicles in presynaptic specializations is the result of sorting mechanisms intrinsic to individual neurons as well as to mechanisms mediated by cell-cell contact. PMID- 1904481 TI - Neuropil threads of Alzheimer's disease show a marked alteration of the normal cytoskeleton. AB - Abnormal neurites, neuropil threads, are a widespread and characteristic lesion of Alzheimer's disease likely to play a major role in the cognitive impairment of this disease. Contrary to normal neurites, neuropil threads contain straight and paired helical filaments that contain the microtubule-associated protein tau and ubiquitin. It is not known whether these abnormal filaments are added to or replace the normal cytoskeleton. In this study, we examined the fine structure of neuropil threads and carried out a morphometric analysis of the neurofilaments and abnormal filaments contained in the neuropil threads by using an antiserum to tau and colloidal gold immuno-electron microscopy. Almost 70% of the neuropil threads contained straight or paired helical filaments with no neurofilaments. The total number of filaments in each neuropil thread remained essentially unchanged either when straight or paired helical filaments were present alone or when they coexisted either together or with neurofilaments. When the three types of filaments were expressed as a proportion of the total, a linear inverse correlation was found between neurofilaments and straight filaments as well as between straight and paired helical filaments. Approximately 10% of the neuropil threads were found to be myelinated axons. It is concluded that straight filaments are likely to replace neurofilaments, that they in turn might be replaced by paired helical filaments, and that this process occurs in axons as well as dendrites. PMID- 1904482 TI - The reproducibility of striatal uptake data obtained with positron emission tomography and fluorine-18-L-6-fluorodopa tracer in non-human primates. AB - Cynomolgus and rhesus monkeys have been studied via PET with [18F]-L-6 fluorodopa tracer. Striatal fluorodopa uptake rate constants have been derived by graphical analysis of transaxial slice images centered on the striata. The differences between pairs of values of the rate constant, obtained from two scans on the same monkey separated by two weeks or more, exhibited a relative standard deviation of 34.4%. If the two scans were conducted one immediately after the other, with the position of the monkey undisturbed, the standard deviation was reduced to 14.0%. The utility of this technique was demonstrated by comparing the effects on the scans of halothane and pentobarbital anesthesia and by the administration of NSD 1015, a peripheral and central inhibitor of L-aromatic amino-acid decarboxylase, between back-to-back scans. With NSD 1015, the fluorodopa uptake constant was reduced by an average of 76.0%. PMID- 1904483 TI - Estimation of glomerular filtration rate in infants and in children using a single-plasma sample method. AB - This work was undertaken to look for distribution volume-plasma clearance converting equations(s) that can be used to estimate glomerular filtration rate (GFR) in children. GFR calculated using the two-blood sample slope-intercept method was used for comparison. It was shown that the 2-hr distribution volume and the two-blood sample clearance were closely related. For all the age groups, the coefficient of correlation between these two parameters was high (range: 0.95 to 0.99) and the s.e.e. was low (range 0.76-3.86 ml/min). It was also shown that a linear equation (GFR = 2,602 V120-0,273) could be used to convert the two hour distribution volume into an accurate estimate of two-blood sample GFR whatever the age of the patient. The use of the single-sample technique for measuring GFR in children is therefore recommendable. PMID- 1904484 TI - Glomerular filtration rate in children: where we have been; where we are going. PMID- 1904485 TI - Oxygen content of the fixative is important in the interpretation of the ultrastructure of ischaemic myocardium. AB - Isolated rat hearts were subjected to 15, 45, or 60 minutes of global ischaemia and then fixed by perfusion at 37 degrees C with glutaraldehyde containing various amounts of oxygen. This either had been bubbled with 100% oxygen (PO2 620 mm Hg) or with 100% nitrogen (PO2 40 mm Hg) immediately before use, or it had been routinely prepared and stored exposed to atmospheric oxygen (PO2 245 mm Hg). The ultrastructure of myocytes and endothelial cells subjected to 15 minutes of ischaemia was not affected by the treatment of the fixative. However, when the tissue subjected to longer periods of ischaemia was fixed with routinely prepared or oxygen-bubbled glutaraldehyde, ultrastructural changes characteristic of reoxygenation damage were uniformly evident in both the microvasculature and myocytes. These qualitatively distinct changes included mitochondrial swelling, cell swelling, endothelial bleb formation, and narrowing of capillary lumina. These abnormalities were not observed in tissue fixed with nitrogen-bubbled glutaraldehyde. These findings indicate that deliberate steps should be taken to reduce or eliminate dissolved oxygen from the fixatives used to study ischaemic tissues. Otherwise artefactual reoxygenation damage in vitro may occur and make valid ultrastructural interpretation difficult or impossible. PMID- 1904486 TI - Influence of calcium and amino acids on the osmium impregnation of the endoplasmic reticulum. AB - The aim of this study was to define further the interaction between osmium and organelle content in cells prefixed with glutaraldehyde. We have studied the reaction of osmium with divalent or trivalent cations (calcium, barium, zinc, aluminum, and iron) and various amino acids in the same conditions prevalent in histological techniques, in particular with Thiery's technique of metal impregnation. Experiments were carried out in vitro in test tubes, on cellulose acetate discs, or with an immunodiffusion apparatus. Some experiments were also carried out with tissue extracts (kidney and intestine). Our studies suggest that calcium is in general essential for the formation of osmium black, but also that lysine is reactive even in the absence of calcium and that a few amino acids- such as tryptophan, ornithine, cysteine, and aspartic acid--are only slightly reactive in the absence of calcium. Other amino acids do not seem to participate in the endoplasmic reticulum osmium impregnation even in the presence of calcium ions. Our studies also suggest that osmium reactivity reflects calcium binding sites and not only calcium content. PMID- 1904487 TI - The role of the low density lipoprotein receptor pathway in the delivery of lipophilic photosensitizers in the photodynamic therapy of tumours. AB - Lipoproteins are now recognized as major blood carriers of many hydrophobic porphyrins and related chromophores which are being investigated as possible photosensitizers in the photodynamic therapy of tumours. In vitro and in vivo studies have demonstrated the role of the low density lipoprotein (LDL) receptor pathway in the delivery of photosensitizers to tumour cells and its importance in porphyrin accumulation by tumours. Lysosomes, which are involved in the cellular processing of LDL, are important intracellular targets in the LDL-porphyrin induced phototoxicity. The use of the LDL receptor pathway as a tool for enhancing the selectivity of photosensitizer delivery to tumour cells appears to be a promising field of research in the photodynamic therapy of tumours. PMID- 1904488 TI - Synergism between electricity and ionizing radiation. AB - Weak direct electric currents which produce little (or no) lethal damage to Escherichia coli bacteria are shown to act synergistically with ionizing radiation, both electromagnetic radiation (X-ray) and charged particles (beta radiation). This synergism greatly enhances the lethal effect of ionizing radiation on bacteria. This is possibly due to increased single-strand breaks in DNA, as detected by the alkaline sucrose gradient method. It is also shown that in cells with thymidine-3H incorporated into their DNA and treated with electricity, the radioactivity is released from the acid-insoluble fraction to the acid-soluble fraction, so that the ratio of radioactivity in the soluble fraction to that in the insoluble fraction increases from 0.47 in the non-treated control cells to 3.46 in the cells treated with an electric current of 1.0 mA (3.0 V) for 30 min, which indicates extensive degradation of cellular DNA. No synergism is detected between electricity and 254 nm UV radiation nor between electricity and X-rays, when these two agents are used sequentially in any order. Electricity alone produces lesions in cell membranes, as shown by electron microscopy. PMID- 1904489 TI - Detection and quantitative estimation of metalloporphyrins in vivo. AB - Spectrofluorometry, radioisotope (RI) labelling and high performance liquid chromatography (HPLC) can be used to estimate photosensitizer concentrations. The biodistribution of porphyrins and metalloporphyrins containing the bifunctional chelating agent diethylenetriamine pentaacetic acid (DTPA) was examined in tumour bearing mice by nitrogen-pulsed laser spectrofluorometry (PLS) and RI labelling. The biodistribution of metalloporphyrin amino acid derivatives containing alkoxyl groups was also examined by PLS and HPLC analysis using an acetone powder extraction method. Spectrofluorometry is useful for estimating the biodistribution of porphyrins in tumour, lung, kidney and serum, but not in liver. However, spectrofluorometry cannot be used to evaluate the concentration of certain metalloporphyrins such as manganese complexes. The concentrations of porphyrins in liver measured by PLS and two other methods showed remarkable differences. RI labelling and HPLC analysis are obviously tedious methods. Therefore it seems practical to screen for a number of compounds using the spectrofluorometric method (PLS). Subsequently, the porphyrins which give good results with PLS should be measured using RI labelling and HPLC. PMID- 1904491 TI - Photobinding of psoralens to DNA in the dark by triplet ketones generated thermally from dioxetanes. PMID- 1904490 TI - Temperature effects on photosensitized processes. AB - The singlet-oxygen-mediated reaction of meso-tetraphenylporphine tetrasulphonate (TPPS4) with different chemical acceptors in buffered aqueous solution was studied as a function of temperature. Imidazole, tryptophan, dimethyl p nitrosoaniline, (RNO) and furfuryl alcohol served as acceptors. The measurements were performed in real time by spectroscopic or electrochemical monitoring of the consumption of the various reagents, acceptors or dissolved oxygen as a function of the absorbed energy. The results show the following increases in the reaction rate over the temperature range 15-45 degrees C: tryptophan (86%), RNO (90%), furfuryl alcohol (150%) and imidazole (210%). The influence of temperature correlated changes in the initial oxygen concentration and pH was investigated. Possible implications of the present results for the synergistic influence of hyperthermia and photodynamic therapy are discussed. PMID- 1904492 TI - Potential use of a charge-coupled device camera for imaging fluorescent dyes in vivo. PMID- 1904493 TI - Characterization of binding of the ATP-sensitive potassium channel ligand, [3H]glyburide, to neuronal and muscle preparations. AB - Binding of the hypoglycemic sulfonylurea, [3H]glyburide, to crude membrane fractions from brain, heart and smooth (intestinal) muscle was saturable, linear with protein concentration and reversible. Saturation analysis revealed high affinity sites (KH values, 7 x 10(-11) M, 5 x 10(-11) M and 6 x 10(-11) M), with Bmax-H values 209, 36 and 23 fmol/mg protein in the brain, heart and smooth muscle, respectively. High affinity [3H]glyburide binding was pharmacologically specific, insensitive to a variety of receptor-active ligands, but sensitive to a series of sulfonylureas, and good, essentially 1:1, correlations were obtained between binding affinities and literature-derived pharmacologic activities. The K+ channel activators, cromakalim, nicorandil, pinacidil and minoxidil were not effective as inhibitors of [3H]glyburide binding. However, diazoxide was a modestly effective inhibitor. Putative low affinity sites (KL values, 3 x 10(-7) M, 1 x 10(-7) M and 2 x 10(-9) M) with Bmax-L values 4956, 336 and 53 fmol/mg protein in brain, heart and smooth muscle, respectively, were identified. Their significance remains to be established. Except for ATP gamma S, the ability of nucleotide triphosphates to inhibit high affinity [3H] glyburide binding was dependent on the presence of Mg++. ADP, in the presence of Mg++, inhibited binding with an IC50 value of 6.3 x 10(-4) M. Nucleotide monophosphates did not inhibit [3H] glyburide binding in the presence or absence of Mg++, whereas in the presence of Mg++, nucleotide triphosphates were equally potent inhibitors of binding. The rank order potency for nucleotide diphosphate inhibition of binding, in the presence of Mg++, is ADP greater than GDP greater than IDP = UDP. In the absence of Mg++, [3H]glyburide binding shows a biphasic response to ADP, and the inhibition of binding by ADP was prevented by ATP. It is suggested that this biphasic response is the result of a second nucleotide binding site. PMID- 1904496 TI - The test-retest reliability of the hyperventilation provocation test. AB - The hyperventilation provocation test (HPT) has been widely used for reproducing symptoms of panics. It is assumed that subjects experience similar symptoms on consecutive occasions of hyperventilation. Fourteen subjects with a history of panics and fourteen without such a history underwent the HPT on two occasions one week apart. In the group of 28 subjects as a whole, there were moderate similarities between the HPTs in both the choice and severity of symptoms reported, even when pre-existing symptoms were controlled statistically. Nevertheless, in the subject-by-subject analysis, many subjects showed no resemblance between the two HPTs in the choice of symptoms. This suggests that many subjects would not show any resemblance between the symptoms experienced in an HPT and those of their latest panic even if hyperventilation occurred in that panic. PMID- 1904494 TI - HMG-CoA reductase inhibitor-induced myopathy in the rat: cyclosporine A interaction and mechanism studies. AB - Recent clinical evidence indicates a potential for skeletal muscle toxicity after therapy with HMG-CoA reductase inhibitors (HMGRIs) in man. Although the incidence of drug-induced skeletal muscle toxicity is very low (0.1-0.2%) with monotherapy, it may increase following concomitant drug therapy with the immunosuppressant, cyclosporine A (CsA), and possibly with certain other hypolipidemic agents. In the Sprague-Dawley rat, very high, pharmacologically comparable dosages (150-1200 mg/kg/day) of structurally similar HMGRIs (lovastatin, simvastatin, pravastatin and L-647, 318) produced dose-related increases in the incidence and severity of skeletal muscle degeneration. Physical signs included inappetence, decreased activity, loss of body weight, localized alopecia and mortality. To evaluate the interaction between HMGRIs and CsA, a rat model of CsA-induced cholestasis was developed. In this 2-week model, the skeletal muscle toxicity of the HMGRIs was clearly potentiated by CsA (10 mg/kg/day). Doses of HMGRIs which did not produce skeletal muscle toxicity when given alone caused between 75 and 100% incidence of myopathy (very slight to marked skeletal muscle degeneration) when CsA was coadministered. Typical light microscopic changes included myofiber necrosis with interstitial edema and inflammatory infiltration in areas of acute injury. Histochemical characterization of the muscle lesion indicated that type 2B fibers (primarily glycolytic white fibers) were most sensitive to this toxicity but that, with prolonged administration, all fiber types were ultimately affected. Results of pharmacokinetic studies in rats treated with various HMGRIs +/- CsA indicated that coadministration of CsA alters the disposition of these compounds, resulting in increased systemic exposure (e.g., increased area under the plasma drug concentration vs. time curve-AUC) and consequent (up to 13-fold) increases in skeletal muscle drug levels. Evaluation of the potential interaction between the HMGRI, lovastatin and CsA at the level of hepatic microsomal metabolism indicated that CsA did not inhibit the metabolism of lovastatin in isolated microsomes from female rats. In light of the above findings, it appears that HMGRI-induced myopathy is a class effect in the rat, which is potentiated by CsA as the result of altered clearance and resultant increased tissue exposure. Cholestasis associated with CsA and HMGRIs may form the basis for decreased elimination and the resultant elevated systemic exposure. Furthermore, this toxicity is muscle fiber-selective and may be associated with impaired skeletal muscle energy metabolism. PMID- 1904495 TI - Probenecid enhances central nervous system uptake of 2',3'-dideoxyinosine by inhibiting cerebrospinal fluid efflux. AB - The effects of probenecid on the pharmacokinetics of 2',3'-dideoxyinosine (ddl) and on the distribution of ddl to cerebrospinal fluid (CSF) and brain tissue were determined in rats during and after a 2-hr i.v. infusion of ddl, 125 mg/kg/hr. Probenecid-treated rats received a loading dose of probenecid followed by an i.v. infusion of probenecid initiated 1 hr before and continued during and for 2 hr after termination of the ddl infusion. Plasma concentrations of probenecid averaged 221 +/- 34 micrograms/ml upon termination of the ddl infusion and 258 +/ 34 micrograms/ml (mean +/- S.D., n = 4) 1 hr later. In the probenecid-treated animals, ddl concentrations were higher in plasma (1.5-fold), brain (1.5-fold) and CSF (5.4-fold) at the termination of the ddl infusion and postinfusion concentrations declined more slowly compared to controls. Postinfusion, the CSF/plasma and brain/plasma ratios steadily increased to a greater extent in the probenecid-treated rats compared to control animals. The time course of plasma, CSF and brain tissue concentrations were analyzed by nonlinear least-squares regression using two different compartmental models, one which neglected the direct exchange of drug between the CSF and brain parenchyma, whereas the other allowed for such exchange to occur and neglected direct vascular transfer of drug to brain tissue. Allowing exchange between the CSF and brain tissue gave slightly improved fitting of the data from both probenecid-treated and control rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1904497 TI - The cost of somatization. AB - Fifty-two consecutive patients referred to a psychiatrist with somatic symptoms of underlying psychiatric disorder were studied. The costs of investigations performed in the general hospital prior to referral to the psychiatrist were assessed. The median cost was pounds 286 but the range was pounds 25-2300. Those costs were determined by the physician's original assessment of the likelihood of organic disease and were independent of the view expressed in the general practitioner's referral letter. This preliminary study indicates the need to understand more fully the determinants of early or late referral of somatization patients to a psychiatrist. The determinants include the diagnostic difficulties of the presenting symptom, patient factors including resistance to adopting a psychological view of the symptoms, and physician factors determining the number of investigations performed to exclude organic disease. PMID- 1904499 TI - A simple handling technique for mammalian oocytes and embryos during preparation for transmission electron microscopy. AB - Due to their small size, mammalian oocytes and embryos pose unique problems during preparation for transmission electron microscopy. This paper outlines a method which combines protein embedding with centrifugation to locate the specimens on the face of a Beem capsule mould. This method facilitates both the processing of oocytes with minimal loss and rapid location of the specimens within the block for simultaneous sectioning, staining and examination. PMID- 1904498 TI - Adenosine transport and nitrobenzylthioinosine binding in human placental membrane vesicles from brush-border and basal sides of the trophoblast. AB - The nucleoside transport activity of human placental syncytiotrophoblast brush border and basal membrane vesicles was compared. Adenosine and uridine were taken up into an osmotically active space. Adenosine was rapidly metabolized to inosine, metabolism was blocked by preincubating vesicles with 2' deoxycoformycin, and subsequent adenosine uptake studies were performed in the presence of 2'-deoxycoformycin. Adenosine influx by brush-border membrane vesicles was fitted to a two-component system consisting of a saturable system with apparent Michaelis-Menten kinetics (apparent Km approx. 150 microM) and a linear component. Adenosine uptake by the saturable system was blocked by nitrobenzylthioinosine (NBMPR), dilazep, dipyridamole and other nucleosides. Inhibition by NBMPR was associated with high-affinity binding of NBMPR to the brush-border membrane vesicles (apparent Kd 0.98 +/- 0.21 nM). Binding of NBMPR to these sites was blocked by adenosine, inosine, uridine, thymidine, dilazep and dipyridamole, and the respective apparent Ki values were 0.23 +/- 0.012, 0.36 +/- 0.035, 0.78 +/- 0.1, 0.70 +/- 0.12 (mM), and 0.12 and 4.2 +/- 1.4 (nM). In contrast, adenosine influx by basal membrane vesicles was low (less than 10% of the rate observed with brush-border membrane vesicles under similar conditions), and hence no quantitative studies of adenosine uptake could be performed with these vesicles. Nevertheless, high-affinity NBMPR binding sites were demonstrated in basal membrane vesicles with similar properties to those in brush-border membrane vesicles (apparent Kd 1.05 +/- 0.13 nM and apparent Ki values for adenosine, inosine, uridine, thymidine, dilazep and dipyridamole of 0.14 +/- 0.045, 0.54 +/- 0.046, 1.26 +/- 0.20, 1.09 +/- 0.18 mM and 0.14 and 3.7 +/- 0.5 nM, respectively). Exposure of both membrane vesicles to UV light in the presence of [3H]NBMPR resulted in covalent labeling of a membrane protein(s) with a broad apparent Mr on SDS gel electropherograms of 77,000-45,000, similar to that previously reported for many other tissues, including human erythrocytes. We conclude that the maternal (brush-border) and fetal (basal) surfaces of the human placental syncytiotrophoblast possess broad-specificity, facilitated-diffusion, NBMPR-sensitive nucleoside transporters. PMID- 1904501 TI - Primary and secondary structure of the nuclear small subunit ribosomal RNA of the cryptomonad Pyrenomonas salina as inferred from the gene sequence: evolutionary implications. AB - The cryptomonad Pyrenomonas salina presumably has arisen from a symbiotic event involving a flagellated phagotrophic host cell and a photosynthetic eukaryote as the symbiont. Correspondingly, in this unicellular alga there are four different genomes, e.g., the nuclear and the mitochondrial genomes of the host cell as well as the plastid genome and the genome contained in the vestigial nucleus of the endocytobiont (nucleomorph). To analyze the origin of one of the symbiotic partners the small subunit rRNA gene sequence of the host cell nucleus was determined, and a secondary structure model has been constructed. This sequence is compared to those of 40 other eukaryotes. A phylogenetic tree constructed using the neighborliness method revealed a close relationship between the host cell of P. salina and the chlorophytes, whereas the rhodophytes diverge more deeply in the tree. PMID- 1904500 TI - Length polymorphism in the threonine-glycine-encoding repeat region of the period gene in Drosophila. AB - Single-fly polymerase chain reaction amplification and direct DNA sequencing revealed high levels of length polymorphism in the threonine-glycine encoding repeat region of the period (per) gene in natural populations of Drosophila melanogaster. DNA comparison of two alleles of identical lengths gave a high number of synonymous substitutions suggesting an ancient time of separation. However detailed examination of the sequences of different Thr-Gly length variants indicated that this divergence could be understood in terms of four deletion/insertion events. In Drosophila pseudoobscura a length polymorphism is observed in a five-amino acid degenerate repeat, which corresponds to melanogaster's Thr-Gly domain. In spite of the differences between D. melanogaster and D. pseudoobscura in the amino acid sequence of the repeats, the predicted secondary structures suggest evolutionary and mechanistic constraints on the per protein of these two species. PMID- 1904502 TI - Angiosperm origin and early stages of seed plant evolution deduced from rRNA sequence comparisons. AB - Complete or partial nucleotide sequences of five different rRNA species, coded by nuclear (18S, 5.8S, and 5S) or chloroplast genomes (5S, 4.5S) from a number of seed plants were determined. Based on the sequence data, the phylogenetic dendrograms were built by two methods, maximum parsimony and compatibility. The topologies of the trees for different rRNA species are not fully congruent, but they share some common features. It may be concluded that both gymnosperms and angiosperms are monophyletic groups. The data obtained suggest that the divergence of all the main groups of extant gymnosperms occurred after the branching off of the angiosperm lineage. As the time of divergence of at least some of these gymnosperm taxa is traceable back to the early Carboniferous, it may be concluded that the genealogical splitting of gymnosperm and angiosperm lineages occurred before this event, at least 360 million years ago, i.e., much earlier than the first angiosperm fossils were dated. Ancestral forms of angiosperms ought to be searched for among Progymnospermopsida. Genealogical relationships among gymnosperm taxa cannot be deduced unambiguously on the basis of rRNA data. The only inference may be that the taxon Gnetopsida is an artificial one, and Gnetum and Ephedra belong to quite different lineages of gymnosperms. As to the phylogenetic position of the two Angiospermae classes, extant monocotyledons seem to be a paraphyletic group located near the root of the angiosperm branch; it emerged at the earliest stages of angiosperm evolution. We may conclude that either monocotyledonous characters arose independently more than once in different groups of ancient Magnoliales or that monocotyledonous forms rather than dicotyledonous Magnoliales were the earliest angiosperms. Judging by the rRNA trees, Magnoliales are the most ancient group among dicotyledons. The most ancient lineage among monocotyledons leads to modern Liliaceae. PMID- 1904503 TI - Lens protein expression in mammals: taxon-specificity and the recruitment of crystallins. AB - Vertebrate lenses show remarkably taxon-specific patterns of protein composition, most obviously in the recruitment of enzymes as major crystallins. Phylogenetic relationships are particularly apparent in mammals. Here we describe eta crystallin, which is probably identical to cytosolic aldehyde dehydrogenase, lens specifically expressed at high abundance in the elephant shrews, primitive eutherians of the family Macroscelidae, and mu-crystallin, a novel lens protein expressed in some marsupials. We have also observed that enzymes that have been recruited as crystallins in some species are also moderately abundant in the lenses of other species. This hints that the origins of enzyme-crystallins may lie in a pool of enzymes widely expressed in lenses at fairly high levels, perhaps because they have important developmental or functional roles in the tissue. PMID- 1904504 TI - Epidemiology of Rh hemolytic disease of the newborn in the United States. AB - Nationwide surveillance of Rh hemolytic disease of the newborn (RhHDN) indicates that, after a substantial decline in incidence, reported rates reached a plateau in the late 1970s. We conducted a study designed to validate RhHDN surveillance data, to obtain corrected incidence estimates, and to identify potential reasons for the reported plateau. We obtained data from the Birth Defects Monitoring Program, a national surveillance system that collects data from public and private hospitals participating voluntarily. We asked hospitals for copies of the medical records for all infants discharged with a code for RhHDN and for a sample of the medical records of infants discharged with a code for other and unspecified hemolytic disease during 1986. The estimated incidence rate of RhHDN was 10.6 per 10,000 total births, with some regional variations. Our findings indicate that, despite the availability of an effective preventive measure, RhHDN continues to contribute significantly to infant morbidity and mortality in the United States. PMID- 1904505 TI - Changing the medical school curriculum to improve patient access to primary care. AB - The problems of access to health care by the underinsured demand a systematic response. One of the critical components of that response is medical curriculum reform, with the intent to graduate adequate numbers of physicians to do primary care, to work with the underinsured and the uninsured, and to practice in rural areas. One state, Minnesota, has developed a unique response to these needs, demonstrating problem solving very much in keeping with many of the recommendations in the literature. Highlighted in this article is the University of Minnesota's Rural Physician Associate Program, a predoctoral curriculum innovation functioning for 20 years to help resolve the issue of physician maldistribution in the state. The Rural Physician Associate Program provides students with many of the skills needed to provide primary care, it is cost effective, and it has brought a number of benefits to the participating communities. PMID- 1904506 TI - The necessary length of hospital stay for chronic pulmonary disease. AB - OBJECTIVE: --To determine the necessary length of stay for patients admitted to the hospital with an exacerbation of chronic pulmonary disease and to compare this with the length of stay assigned by the diagnosis related group system. DESIGN: --A cohort of patients were followed up prospectively after hospital admission to determine when complications, critical incidents, and the need for monitoring occurred. The medically derived necessary lengths of stay were statistically compared with the lengths of stay assigned by the diagnosis related group. Clinical factors were used to predict long vs short necessary lengths of stay. SETTING: --Two acute care hospitals: one was the principal and the other a major community teaching hospital. PATIENTS: --A consecutive sample of 83 patients who were 45 years of age or older and who required admission for treatment of chronic pulmonary disease. MAIN OUTCOME MEASURES: --The occurrence and time of complications, critical interventions, and monitoring. RESULTS: - After 6 days in the hospital, 90% of patients were free of complications or the need for monitoring. However, 16 days elapsed before 90% of patients had been discharged from the hospital. The length of stay that was considered necessary for care averaged 6.9 days; the actual mean length of stay was 8.7 days. The correlation between each patient's ideal length of stay and the length of stay assigned by the diagnosis related group was low and was not statistically significant. Three clinical variables at the time of admission (high PCO2 levels, symptoms that were present for more than 1 day, and antibiotic treatment) were associated with the need for longer hospital stays. CONCLUSIONS: --The medically required length of stay for patients with an exacerbation of chronic pulmonary disease was between 6 and 7 days, on average. This length of stay, which was based on clinical events, differs from the length of stay that was calculated as a statistical norm by the diagnosis related group system. Clinical characteristics may help to identify patients who require a longer length of stay. PMID- 1904507 TI - [Clinical study on long-term treatment of chronic hepatitis C with interferon]. AB - We treated 41 chronic hepatitis C patients with recombinant interferon alpha 2a, 6 X 10(6) IU/day, for three weeks daily followed by intermittent therapy, 3 X 10(6) IU/day, three times weekly for 6 months and more. After 6 months of intermittent therapy, serum aminotransferases (AST, ALT) decreased to normal or nearly normal levels in 29 of 41 patients (70.7%) with histological improvement. The HCV (C100-3) antibody disappeared during and after IFN therapy in 7 of 34 HCV antibody positive patients (20.6%). Serum aminotransferases levels of all such patients were normalized or nearly normalized. The IFN antibody was detected in 8 of 41 patients (19.5%) including one whose IFN antibody was already present before starting IFN therapy. IFN treatment was discontinued in 22 of 41 patients (53.7%) because they responded completely or nearly completely to IFN therapy. All of the 22 patients have been maintaining normal aminotransferase levels for 1 to 24 months (mean, 12 months) after the treatment period. We conclude that long term IFN therapy is greatly beneficial in controlling hepatic inflammatory changes in chronic hepatitis C. PMID- 1904508 TI - [A case of mid-esophageal diverticulum with mucosal bridge caused by tuberculosis of the apex of the right lung]. PMID- 1904509 TI - [The early detection of metastatic differentiated thyroid cancer using 131I total body scan and treatment with 131I]. AB - With the purpose of achieving early detection and performing 131I therapy for metastatic lesions of differentiated thyroid cancer, we studied the clinical findings in 132 patients who underwent 131I total body scanning (131I TBS) between 1981 and 1990. Metastatic lesions were detected only by 131I TBS in 24 (18%) of the 132 patients. Of the 49 patients treated with 131I for metastases, 27 (55%) underwent total thyroidectomy and then had their metastatic lesions treated by 131I less than one year later. In the remaining 22 patients (45%), the metastatic lesions were treated with 131I from 1 to 31 years (mean: 8.4 years) after the initial thyroidectomy. We determined the optimal timing of 131I TBS following radical thyroidectomy to be 3-4 weeks by sequential measurement of the serum thyroid hormones, TSH, and Tg, and determination of the 123I uptake in residual or metastatic cancer of the neck after thyroidectomy. 131I TBS with simultaneous serum Tg determination were performed in 52 patients with metastases. Scans were positive in 43 of the 52 (83%) and the serum Tg level was greater than 10 ng/ml in 46 of the 52 (88%). Serum Tg was elevated in 9 patients with negative scans, while low Tg levels were found in 6 patients with positive scans. 131I therapy was effective in 49 of the 65 treated patients (75%), including 5 cures. Two patients worsened and 6 died. These 8 patients were all older than 56 years of age. Post-therapeutic 131I TBS demonstrated unsuspected metastatic lesions in 7 patients and had a higher detection rate for metastatic lesions than diagnostic 131I TBS. We conclude that 131I TBS with simultaneous Tg determination should be performed to detect metastatic lesions in all patients following positively total thyroidectomy for differentiated thyroid cancer, and that 131I treatment should be given when positive 131I uptake is detected in metastatic or residual cancer. PMID- 1904510 TI - [Effects of verapamil and nitroglycerin on experimental occlusion- reperfusion induced myocardial infarction in rabbits]. PMID- 1904511 TI - [Gravitational sensitivity of eukaryotic unicellular organisms]. AB - Unicellular organisms are viewed as the best suitable objects for studying environmental effects, including the field of gravity, on living beings at the cellular level. Investigations of unicellular free-living eukaryotic organisms in gravitational and space biology help resolve both theoretical problems and practical problems associated with the design and development of biological life support systems. This paper presents experimental data about the effect of hypergravity on the structure, function and behavior of unicellular organisms- Tetrahymena pyriformis and Euglena gracilis. They were centrifuged at a rate of 87, 108 or 142 rpm to produce acceleration of 2, 3 or 5 G. The following parameters were measured: time course variations in the culture growth, rate of biomass accumulation, cell shape and size. It was found that as the gravity level grew from 2 to 5 G the culture growth was first stimulated and then inhibited. Biomass accumulation as well as the cell size and volume of Tetrahymena pyriformis and Euglena gracilis also decreased. It was demonstrated that the functional activity of cells was inversely proportional to the gravity magnitude. Potential mechanisms of the effect of hypergravity on the cell structure and function are discussed. PMID- 1904512 TI - [The state of bone tissue in monkeys in experiments in the Cosmos-1887 biosatellite]. AB - Using invasive and noninvasive techniques, we studied bone changes in primates flown for 13 days on Cosmos-1887 and compared them with the data obtained from vivarium control animals and from the flown primates that were after flight exposed to a ground-based synchronous experiment in the biosatellite mockup. It was found that bone density in the diaphysis of the tibia decreased while its growth rate remained unchanged or diminished. Contact X-raying indicated a higher rate of endosteal resorption in the flown primates when compared with the controls. Histomorphometric measurements of iliac bioptates displayed signs of inhibited bone formation after flight. The above observations are discussed and compared with the results obtained in previous biosatellite flights and ground based studies. PMID- 1904513 TI - Differentiation characteristics of newly established medulloblastoma cell lines (D384 Med, D425 Med, and D458 Med) and their transplantable xenografts. AB - Three new human medulloblastoma (MB) cell lines (D384 Med, D425 Med, and D458 Med) and their transplantable xenografts were examined for antigenic expression with antibodies against neuroectodermal antigens, cytoskeletal proteins, neuroendocrine markers, glioma-associated antigens, tenascin, human lymphocyte antigen molecules, epidermal growth factor receptor, and T-cell antigen by indirect immunofluorescence, avidin-biotin complex peroxidase immunohistochemistry, and immunoblot methods. We found that each of the three cell lines expressed vimentin; low-, middle-, and high-molecular-weight neurofilament proteins; and the synaptic vesicle membrane glycoprotein synaptophysin. Each of the cell lines also reacted with antibodies against neural cell adhesion molecules, but none of them were positive for antibodies against glial fibrillary acidic protein, keratin, microtubule-associated protein tau and microtubule-associated protein 2, human lymphocyte antigen-DR, epidermal growth factor receptor, and T-cell antigen. Immunoreactivities with anti-tenascin and anti-glioma-associated antibodies were variable in these cell lines. Anti-human lymphocyte antigen-A,B and anti-beta 2-microglobulin antibodies reacted with xenografts of D384 Med and D425 Med and were weakly positive for a small population of D384 Med cultured cells. In summary, the detection of neurofilament proteins and synaptophysin and the absence of glial fibrillary acidic protein provide strong evidence for a neuronal phenotype of D384 Med, D425 Med, and D458 Med. PMID- 1904514 TI - A rapidly fatal overdose with flecainide. PMID- 1904515 TI - Regulation of TNF-alpha, IL-1 and IL-6 synthesis in differentiating human monoblastoid leukemic U937 cells. AB - The human monoblastoid tumor cell line U937 was induced to differentiate along the monocyte/macrophage lineage by treatment with 5 x 10(-9) M 12-O-tetradecanoyl phorbol-13-acetate (TPA). Between 2 h and 4 h following TPA-treatment U937 cells started to release significant amounts of TNF-alpha which remained detectable until 8-10 days. A significant IL-1 beta release was measured 24 h-48 h post stimulation and increased levels of IL-1 beta persisted until 20-22 days of culture. In contrast no release of either IL-1 alpha or IL-6 could be detected with 5 x 10(-9) M TPA during the whole time course of the experiments. The sequential induction of TNF-alpha and IL-1 beta appeared to be independently regulated since TNF-alpha release was not required for the onset of IL-1 beta production. Northern-blot analysis confirmed the sequential induction and the long term expression of TNF-alpha and IL-1 beta mRNAs. Western-blot analysis predominantly showed a high molecular weight IL-1 beta protein of about 35 kD. Further investigations on the regulation of cytokine production and release by TPA-differentiated U937 cells revealed that TNF-alpha and IL-1 beta synthesis was not influenced by exogenously added rhTNF-alpha or PGE2, whereas rh gamma-IFN specifically enhanced the IL-1 beta production. Thus, the regulation and intracellular processing of cytokines generated by differentiating U937 cells shows some differences when compared to mature monocytes/macrophages which may be related to the tumorigenic origin of U937 cells or to an incomplete differentiation. PMID- 1904516 TI - A proposed prototype for identifying and correcting sources of measurement error in classification systems. AB - Because many raters are generally involved in the implementation of a patient classification system, interrater reliability is always a concern in the development and use of such a system. In this article, a case example is used to demonstrate a prototype for identifying measurement error introduced at each step in the classification process (assessment, creating summary item responses, and use of these responses for categorization) and to illustrate how this identification may lead to error reduction strategies. The methods of analyses included percent agreement, Kappa, and visual inspection of contingency tables displaying interrater responses to assessment items, summary items, and the placement category. The extent to which raters followed instructions was analyzed by comparing their responses with computer-generated responses across the classification steps. In addition, raters were interviewed regarding their use of the system. PMID- 1904517 TI - Process, costs, and outcomes of community-based prenatal care for adolescents. AB - An evaluation of a community-based prenatal care program for teens compared 180 adolescent clients with a sample of adolescents matched on age and year of delivery who received care through a traditional prenatal care program at a university medical center. Evaluation criteria describing the process of receiving care were the mean number of prenatal visits, nonscheduled outpatient visits, nonstress tests, ultrasounds, and inpatient days during pregnancy. The two programs were significantly different as measured by these criteria. Outcome criteria included gestational age, birthweight, the percentage of infants requiring neonatal intensive care, and the percentage of clients with maternal complications. A multivariate analysis showed no statistically significant differences in these outcomes. The average cost of resources consumed during prenatal care for the study group was 41% that of controls. PMID- 1904518 TI - Using DRGs to pay for inpatient substance abuse services: an assessment of the CHAMPUS reimbursement system. AB - In October 1988, the Civilian Health and Medical Program of the Uniformed Services (CHAMPUS) introduced a prospective payment system based on diagnostic related groups (DRGs) to pay for substance abuse services. These services were initially excluded from the new payment system because of concerns that a DRG based system may have a large and poorly understood financial impact on individual hospitals. This report assesses the performance of a DRG system in explaining variation in costs at the individual patient level and evaluates how well this payment system predicts resource use across hospitals. Overall, the substance abuse DRGs explained only 4.2% of the total variance in charges. It was found that the Medicare DRG-based system had to be modified to reflect the characteristics of the younger CHAMPUS population by splitting DRG 435 to account for the increased costliness of beneficiaries younger than 21 years. In addition, the study revealed substantial variation in the impact of the DRG system on hospital revenue. These differences largely reflected significant differences between general and specialty hospitals. PMID- 1904519 TI - Patients requiring at least five admissions in 1 year. Data from Washington State. PMID- 1904520 TI - [The administration of factor VIII concentrates to hemophiliacs by continuous perfusion pump]. AB - BACKGROUND: The administration of factor VIII (FVIII) in continuous infusion (CI) to hemophiliac inpatients is a therapeutic approach made possible by the development of new commercial preparations. METHODS: In the present study the outcome of 14 treatment courses of FVIII in CI to 12 patients with hemophilia A (2 of them with inhibitor) was evaluated. A computer program developed by the authors is presented. This program is simple and can be executed in any compatible personal computer, permitting the calculation of initial and maintenance doses and individual pharmacokinetic parameters. RESULTS: The hemostatic result was excellent: constant FVIII plasma levels were achieved, and unnecessary overdoses were prevented. Mean infusion rates of 1.99 +/- 0.45 IU/kg/h, 1.47 +/- 0.28 IU/kg/h, and 0.86 +/- 0.12 IU/kg/h were enough to maintain FVIII plasma levels of 1 IU/ml, 0.3 IU/ml, and 0.3 IU/ml, respectively. This represents a saving of 20-50% of the requirements of the traditional intermittent method. CONCLUSIONS: The infusion of intravenous CI of FVIII and the use of a computer program permitting an easy individualization of the treatment schedule resulted in the same hemostatic effectiveness as with the traditional intermittent method, but using a smaller replacement dose. PMID- 1904521 TI - [8 cases of ectopic localization of schistosomiasis in Spanish travelers]. AB - In this article 8 patients with ectopic features due to skin or prostatic deposition of ova of different schistosomal species are reported. The clinical, pathological and radiological features of these lesions are described. It is to be remarked that 7 patients had traveled to Mali and had bathed in the Bandiagara District, which is included in several tourist routes such as "Travel to Dogon country". PMID- 1904522 TI - Comparison of the anti-scorbutic activity of L-ascorbic acid and Ester C in the non-ascorbate synthesizing Osteogenic Disorder Shionogi (ODS) rat. AB - The Osteogenic Disorder Shionogi (ODS) rat, Clea Inc., Tokyo, Japan lacks the ability to synthesize L-ascorbic acid (AA). As with man, monkey and the guinea pig, this rat lacks L-gulonolactone oxidase necessary for the synthesis of AA from glucose. This study shows this animal to be an alternative to the guinea pig in AA studies. The anti-scorbutic potency of Ester C (EC), a calcium ascorbate and calcium threonate mixture, was compared with an AA dose of equal ascorbate activity equivalents (AAE) for anti-scorbutic activity in the ODS rat. The minimal anti-scorbutic dose of EC was determined to be 0.44 mg/kg/day (AAE), while an AA dose of 0.51 mg/kg/day (AAE) was not anti-scorbutic in a 24 day study. At 24 days EC rats gained 125% of initial body weight (BW) and the AA rats only 45% BW. Scorbutic signs at 24 days were scored on a 0 (min) to 3 (max) scale. The EC/AA ratio scores were: hemorrhage 0/1.4, behavior change 0/2.0, piloerection 0/2.2, mobility 0.4/2.2, dysbasia 0.6/2.8 and ataxia 0.4/1.0. Pearson's correlation coefficient for BW versus AAE was r = .34 for the AA group and r = .90 for the EC group. The morbidity index for EC was 0/5 and for the AA group 2/5. The AAE dose of AA which was 16% higher/day than the EC AAE dose was not anti-scorbutic, while the EC dose was anti-scorbutic. EC rats had 3.5X greater weight gain, a sensitive indicator of scurvy, than the AA rats. EC rats had 3-4 times less, if any, scorbutic signs than AA rats. The results clearly show that, based on ascorbate activity equivalents, EC has more available ascorbate activity/potency than AA. The mechanism of this increased potency is believed to be due to the facilitated transport of AAE into the cell by the threonate (a normal in vivo metabolite of AA) present in the EC product. In addition, previous studies have shown EC (AAE) to be higher in plasma and excreted less rapidly than the AAE derived from AA administered orally. PMID- 1904523 TI - Interferon gamma modulates production of interleukin 1 and tumor necrosis factor by murine Kupffer cells. AB - When mononuclear phagocytes, including Kupffer cells, are activated by various agents, they synthesize and release cytokines such as interleukin 1 (IL-1) and tumor necrosis factor (TNF). In this study, we examined the effect of in vitro Kupffer cell activation by recombinant murine interferon gamma (IFN gamma) on IL 1 and TNF secretion. IFN gamma enhanced TNF production in the presence or absence of lipopolysaccharide (LPS), but suppressed IL-1 production by Kupffer cells. Because IFN gamma also stimulated prostaglandin E2 (PGE2) production, the effect of indomethacin, which is an inhibitor of cyclooxygenase and which inhibits PGE2 biosynthesis, on IL-1 and TNF production by Kupffer cells was examined. As a result, indomethacin enhanced TNF production by Kupffer cells, but had no effect on IL-1 synthesis. These results suggested that IFN gamma modulates the production of IL-1 and TNF by Kupffer cells through different mechanisms. PMID- 1904524 TI - Catabolite repression of alpha-amylase gene expression in Bacillus subtilis involves a trans-acting gene product homologous to the Escherichia coli lacl and galR repressors. AB - Expression of the alpha-amylase gene of Bacillus subtilis is controlled at the transcriptional level, and responds to the growth state of the cell as well as the availability of rapidly metabolizable carbon sources. Glucose-mediated repression has previously been shown to involve a site near the transcriptional start-point of the amyE gene. In this study, a transposon insertion mutation was characterized which resulted in loss of glucose repression of amyE gene expression. The gene affected by this mutation, which was localized near 263 degrees on the B. subtilis chromosomal map, was isolated and its DNA sequence was determined. This gene, designated ccpA, exhibited striking homology to repressor genes of the lac and gal repressor family. The ccpA gene was found to be allelic to alsA, previously identified as a regulator of acetoin biosynthesis, and may be involved in catabolite regulation of other systems as well. PMID- 1904525 TI - Gas vesicle synthesis in the cyanobacterium Pseudanabaena sp.: occurrence of a single photoregulated gene. AB - Gas vesicles are subcellular inclusions found in a large number of aquatic prokaryotes. The gvpA gene, which frequently occurs as a multigene family, encodes the major gas vesicle structural protein. In several cyanobacteria, another gene, gvpC, encodes a different protein which might be a dispensable element for gas vesicle formation. We report here the molecular characterization of a gvpA gene in Pseudanabaena sp. PCC 6901. In this planktonic cyanobacterium, it is the only gvp gene which could be detected, and electrophoretic analysis of isolated gas vesicles revealed the presence of a single protein. A monocistronic mRNA species corresponds to the transcription of the gvpA gene and the abundance of the gvpA mRNA is inversely correlated with photosynthetic photon flux indicating that a light-dependent transcriptional regulation is likely to be involved in the control of gas vacuolation in this strain. PMID- 1904526 TI - Comparison of the class 1 outer membrane proteins of eight serological reference strains of Neisseria meningitidis. AB - Primers suitable for the amplification of the gene encoding the class 1 outer membrane protein of Neisseria meningitidis by the polymerase chain reaction (PCR) were designed from published DNA sequences and used to study the gene in eight meningococcal strains of different serogroup, serotype and subtype. At high annealing stringency one product, shown to correspond to the class 1 protein gene, was amplified from each strain. For three strains an additional smaller product, provisionally identified as the gene encoding the class 3 outer membrane protein, was amplified at lower annealing stringencies. Nucleotide sequence analysis of the PCR products corresponding to the class 1 proteins established the differences in the primary structure of the proteins between each of the subtypes and other outer-membrane proteins from Neisseria spp. These differences impose constraints on possible structural models of these proteins. Most amino acid sequence variation occurred in two domains of between 8 and 17 amino acids; there was an additional region which varied mainly between classes of outer membrane protein and there were nine conserved regions. Using appropriate primers it was possible to distinguish between class 1 outer membrane protein genes from strains of different subtypes by the PCR. PMID- 1904527 TI - The role of sigma F in prespore-specific transcription in Bacillus subtilis. AB - Sporulation in Bacillus subtilis is a simple developmental system in which a single cell undergoes differentiation to two 'sister' cells, namely the prespore and the sporangium. Prespore-specific gene expression is largely dependent on the synthesis of a transcription factor, sigma G. Transcription of spolllG, the gene encoding sigma G, is under precise temporal and spatial control, requiring the products of at least eight genes that are expressed in the pre-divisional cell. Here we show that the product of one of these genes, another sigma factor, sigma F, is by itself sufficient to direct transcription of spolllG in non-sporulating cells. The results indicate that the cell-specificity of prespore gene expression is determined by a mechanism that exerts temporal and spatial control over the activity of sigma F. PMID- 1904528 TI - Acute and subacute fulminant hepatic failure: the role of liver transplantation. AB - OBJECTIVES: To report the experience of the Australian National Liver Transplant Unit with patients with fulminant hepatic failure and to describe the role of liver transplantation. PATIENTS: Twenty-seven patients presented with acute or subacute fulminant hepatic failure during the period from January, 1986, to March, 1990. Twenty-two had acute and five had subacute fulminant hepatic failure. The causes were hepatitis B in 10 patients, presumed non-A, non-B (NANB) hepatitis in eight patients, drug-induced hepatic damage in five patients, and Wilson's disease in four patients. There were 13 males and 14 females. Ages were 2-43 years (mean, 23). Twenty patients (74%) were in grade IV encephalopathy on presentation. RESULTS: Six patients (22%) began to improve soon after admission and went on to full recovery. Spontaneous recovery was more frequent in patients with drug-induced hepatic damage (four patients [80%]) and was less frequent in those with hepatitis B (one patient [10%]) and NANB hepatitis (one patient [12%]). The other 21 patients (78%) were considered for orthotopic liver transplantation. Eight (30%) were judged to be unsuitable and went on to early death. Thirteen (48%) were suitable for transplantation. Of these five (19%) died before a liver donor became available and eight (30%) received liver grafts and went on to full recovery. Overall, 14 patients (52%) survived and 13 (48%) died. Patients with Wilson's disease (four [100%]) were most suitable for orthotopic liver transplantation whereas eight (44%) of those with hepatitis B or NANB hepatitis were unsuitable. Of the eight patients receiving liver grafts one had hepatitis B, three had NANB hepatitis and four had Wilson's disease. Five were in grade IV encephalopathy at the time of operation. The mean waiting time for transplantation was 6.4 days. Five patients received ABO blood group compatible grafts and three received ABO incompatible grafts. Of the latter group, two subsequently required secondary orthotopic liver transplantation with ABO compatible grafts. All eight patients who received transplants are alive and well 3-24 months after the operation. No patient has any neurological sequelae. CONCLUSIONS: Orthotopic liver transplantation is a preferred option for patients with fulminant hepatic failure whose condition is not responding to conservative management. ABO incompatible livers transplanted in emergency circumstances may prove life-saving either by functioning successfully or by providing time during which ABO compatible grafts become available.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1904529 TI - Investigation of the relative surface dose from Lipowitz-metal tissue compensators for 24- and 6-MV photon beams. AB - Our radiation therapy department has acquired a tissue compensator system for construction of patient-specific Lipowitz-metal tissue compensators. Since the arrival of this apparatus its use has been limited due to the observance of marked skin reactions located directly beneath the area of the compensator. Although there has been extensive literature on the dose distribution of these metal compensators, there is little data on the effects to the skin for energies greater than 10 MV. Determination of the relative surface dose from Lipowitz metal tissue compensators is herein investigated for 24- and 6-MV x-ray beams. Effects of field size, source-to-skin distance and thickness of compensator are evaluated as well as the effect of the Lexan tray which supports the compensator during treatment. PMID- 1904530 TI - Depth dose characteristics of 24-MV x-ray beams at extended SSD. AB - Depth dose characteristics of 24-MV beams from a medical linear accelerator at various SSDs have been measured. The dose buildup, percent depth dose (PDD), and output were measured using ionization chambers and a diode detector under full scatter. Surface dose ranged from 8% to 51% depending upon the collimator setting at 100-cm SSD. It decreased by 10%-15% as distance was increased to 200 cm, but remained unchanged beyond this distance. The dmax migrated rapidly toward the surface with increasing field size at 100-cm SSD. At extended SSD, the dmax occurred at greater depths and shifted a little toward the shallow depths with increasing field size. Large field PDDs measured at extended SSD agreed well with those predicted from 100-cm data. The output followed the 1/(distance)2 relationship quite well. The extended SSD beam data are clinically useful when treating hemibody or performing total body irradiation (TBI) procedures. PMID- 1904531 TI - Effects of age on behavioral and physiological responses to carbaryl in rats. AB - Motor, sensory and thermoregulatory functions were examined in young (3 months) and mature (12 months) rats following PO administration of single low doses (10 and 50 mg/kg) of carbaryl, a carbamate insecticide, and these effects were related to blood cholinesterase activity. Carbaryl 50 mg/kg decreased the frequency of ambulation in the open-field arena within 30 min while it enhanced the duration of haloperidol-induced catalepsy in both young and mature rats. Administration of carbaryl also resulted in an increased nociceptive threshold to thermic stimuli mainly in mature rats. An age-related reduction in body temperature was observed at 30, 60 and 90 min after injection. Activity of blood cholinesterase was reduced in young and mature rats at 30 and 60 min following carbaryl exposure. These results indicate that carbaryl can induce an age-related impairment on some behavioral and autonomic functions in rats correlated to the inhibition of cholinesterase activity. PMID- 1904532 TI - Identification and initial utilization of a portion of the smaller plasmid of Anabaena variabilis ATCC 29413 capable of replication in Anabaena sp. strain M 131. AB - Anabaena variabilis ATCC 29413 contains two cryptic plasmids. Clones of the smaller (41 kb) plasmid, designated pRDS1, in cosmid vectors were used to construct a physical map. A clone bank of pRDS1 constructed by ligating fragments from a XhoII digest of a pRDS1 cosmid clone into a mobilizable plasmid was used to locate an origin of replication of pRDS1. Because we were unable to cure A. variabilis of pRDS1, the clone bank was transferred by conjugation to another strain of Anabaena sp., strain M-131. A 5.3 kb fragment of pRDS1 contained all of the sequences necessary for replication in Anabaena sp. strain M-131 as judged by the ability to rescue the hybrid vector from exconjugants in unchanged from after many generations. Hybrid plasmids derived from pRDS1, one bearing genes for luciferase, were also transferred by conjugation to A. variabilis, where they appeared to recombine with pRDS1. PMID- 1904533 TI - Identification and characterization of two entry exclusion genes of the promiscuous IncP plasmid R18. AB - Two entry exclusion genes (designated eexA and eexB) from the promiscuous IncP alpha plasmid R18 have been isolated by molecular cloning. They are located between coordinates 26.6-27.4 kb and 27.4-27.6 kb, respectively and are transcribed clockwise on the conventional R18 map. The product of the eexA gene has an apparent molecular mass of 28 kDa and its N-terminus contains a putative signal sequence for protein export. A recombinant plasmid containing R18 eex genes exerted Eex activity towards another promiscuous IncP alpha plasmid, R702, about 50 times more strongly than plasmid R18 itself. Analysis of the DNA sequence revealed no similarity to the eex genes of the F plasmid of Escherichia coli. R18 eexA includes a potential korB binding site and is followed by a potential transcription terminator. A Tn7 insertion at coordinate 20.0 kb of R18 resulted in a host range mutant pM01185, which leads to loss of Eex activity and of conjugative transfer of the plasmid into some bacterial species. PMID- 1904535 TI - A beta-galactosidase deletion mutant of Lactobacillus bulgaricus reverts to generate an active enzyme by internal DNA sequence duplication. AB - Several spontaneous Lac- deletion derivatives of the beta-galactosidase gene of Lactobacillus bulgaricus were analyzed for their phenotypic stability. We found that one of these mutants, lac139, carrying a deletion of 30 bp within the gene, was able to revert to a Lac+ phenotype. Genetical analysis of revertants indicated that an internal region of 72 bp was duplicated immediately next to the deletion site. The region involved in the duplication event is flanked by direct repeated sequences of 13 bp in length. Both events, the deletion and the duplication, were mediated by the presence of such short direct repeats. Enzymatic studies of the purified proteins indicated identical kinetic parameters, but showed considerable instability of the revertant protein. PMID- 1904534 TI - Preprosubtilisin Carlsberg processing and secretion is blocked after deletion of amino acids 97-101 in the mature part of the enzyme. AB - During an investigation into the substrate specificity and processing of subtilisin Carlsberg from Bacillus licheniformis, two major independent findings were made: (i) as has been shown previously, a stretch of five amino acids (residues 97-101 of the mature enzyme) that loops out into the binding cleft is involved in substrate binding by subtilisin Carlsberg. In order to see whether this loop element also determines substrate specificity, the coding region for these five amino acids was deleted from the cloned gene for subtilisin Carlsberg by site-directed mutagenesis. Unexpectedly the resulting mutant preproenzyme (P42c, Mr = 42 kDa) was not processed to the mature form (Mr = 30 kDa) and was not released into the medium by a protease-deficient B. subtilis host strain; rather, it accumulated in the cell membrane. This result demonstrates that the integrity of this loop element, which is very distant from the processing cleavage sites in the preproenzyme, is required for secretion of subtilisin Carlsberg. (ii) In culture supernatants from B. subtilis harbouring the cloned wild-type subtilisin Carlsberg gene the transient appearance (at 0-3 h after onset of stationary phase) of a processing intermediate (P38c, Mr = 38 kDa) of this protease could be demonstrated. P38c very probably represents a genuine proform of subtilisin Carlsberg. PMID- 1904536 TI - Genetic analysis of a lactococcal plasmid replicon. AB - The sequence and genetic organization was determined of the 2508 bp lactococcal portion of pFX2, which was derived from a cryptic Lactococcus lactis subsp. lactis plasmid and used as the basis for construction of a series of lactococcal vectors. A lactococcal plasmid plus origin and two replication protein-coding regions (repA and repB) were located. RepA has a helix-turn-helix motif, a geometry typical of DNA-binding proteins. RepB shows a high degree of homology to the plasmid replication initiation proteins from other gram-positive bacteria and Mycoplasma. The transcribed inverted repeat sequence between repA and repB could form an attenuator to regulate pFX2 replication. Up-stream of the ori site, and in a region which was non-essential for replication, a 215 bp sequence identical to the staphylococcal plasmid pE194 and carrying the RSA site was identified. The genetic organization of this lactococcal plasmid replicon shares significant similarity with pE194 group plasmids. PMID- 1904537 TI - Signal peptidase I overproduction results in increased efficiencies of export and maturation of hybrid secretory proteins in Escherichia coli. AB - The effects of 25-fold overproduction of Escherichia coli signal peptidase I (SPase I) on the processing kinetics of various (hybrid) secretory proteins, comprising fusions between signal sequence functions selected from the Bacillus subtilis chromosome and the mature part of TEM-beta-lactamase, were studied in E. coli. One precursor (pre[A2d]-beta-lactamase) showed an enhanced processing rate, and consequently, a highly improved release of the mature enzyme into the periplasm. A minor fraction of a second hybrid precursor (pre[A13i]-beta lactamase), which was not processed under standard conditions of SPase I synthesis, was shown to be processed under conditions of SPase I overproduction. However, this did not result in efficient release of the mature beta-lactamase into the periplasm. In contrast, the processing rates of wild-type pre-beta lactamase and pre(A2)-beta-lactamase, already high under standard conditions, were not detectably altered by SPase I overproduction. These results demonstrate that the availability of SPase I can be a limiting factor in protein export in E. coli, in particular with respect to (hybrid) precursor proteins showing low (SPase I) processing efficiencies. PMID- 1904538 TI - Distance-dependent translational coupling and interference in Lactococcus lactis. AB - The possibility of raising the expression level of a heterologous gene in Lactococcus lactis by exploiting the principle of translational coupling was investigated. For this purpose, the Escherichia coli lacZ gene was transcriptionally fused to a short open reading frame (ORF) of lactococcal origin. A Shine-Dalgarno (SD) sequence was introduced at the boundary of the two ORFs. In a series of otherwise identical plasmids, the relative positions of the translational stop codon of the upstream ORF and the translational start codon of the downstream ORF (lacZ) were varied. The expression of lacZ gradually increased as the stop and start codons were placed in closer proximity. A concomitant switch from translational interference to translational coupling was observed. Best results were obtained with partially overlapping stop and start codons. It is concluded that the principle of translational coupling offers good possibilities to increase the level of heterologous gene expression in L. lactis. PMID- 1904539 TI - Expression of the dnaA gene of Escherichia coli is inducible by DNA damage. AB - The DnaA protein is the key DNA initiation protein in Escherichia coli. Using transcriptional and translational fusions, comparative S1 nuclease mapping and immunoblot analysis, the regulation of dnaA in relation to inducible responses to DNA damage was studied. We found that DNA damage caused by mitomycin C (MC) and methyl methanesulfonate (MMS) led to a significant induction of the dnaA gene. These results strongly suggest that in response to DNA damage which inhibits DNA replication, an increased initiation capacity is induced at oriC and that, in addition to the known auto-repression, a new regulatory mechanism may be involved in the control of dnaA gene expression. Furthermore, this mechanism might be indirectly related to the SOS regulon, because lexA and recA mutants, which block the induction of the SOS response, prevent dnaA induction by MMS and MC. PMID- 1904540 TI - Modular recognition of 5-base-pair DNA sequence motifs by human heat shock transcription factor. AB - We investigated the recognition of the conserved 5-bp repeated motif NGAAN, which occurs in heat shock gene promoters of Drosophila melanogaster and other eukaryotic organisms, by human heat shock transcription factor (HSF). Extended heat shock element mutants of the human HSP70 gene promoter, containing additional NGAAN blocks flanking the original element, showed significantly higher affinity than the wild-type promoter element for human HSF in vitro. Protein-DNA contact positions were identified by hydroxyl radical protection, diethyl pyrocarbonate interference, and DNase I footprinting. New contacts in the mutant HSE constructs corresponded to the locations of additional NGAAN motifs. The pattern of binding indicated the occurrence of multiple DNA binding modes for HSF with the various constructs and was consistent with an oligomeric, possibly trimeric, structure of the protein. In contrast to the improved binding, the extended heat shock element mutant constructs did not exhibit dramatically increased heat-inducible transcription in transient expression assays with HeLa cells. PMID- 1904541 TI - Mutational analysis of CDC42Sc, a Saccharomyces cerevisiae gene that encodes a putative GTP-binding protein involved in the control of cell polarity. AB - The Saccharomyces cerevisiae CDC42 gene product, a member of the ras superfamily of low-molecular-weight GTP-binding proteins, is involved in the control of cell polarity. We have analyzed the effects of three CDC42 mutations (Gly to Val-12, Gln to Leu-61, and Asp to Ala-118) in the putative GTP-binding and hydrolysis domains and one mutation (Cys to Ser-188) in the putative isoprenylation site. The first three mutations resulted in either a dominant-lethal or dose-dependent dominant-lethal phenotype when present on plasmids in haploid cdc42-1ts or wild type strains. Both wild-type and cdc42-1ts cells carrying plasmids (pGAL) with either the CDC42Val-12 or CDC42Leu-61 alleles under the control of a GAL promoter were arrested with a novel phenotype of large cells with elongated or multiple buds. Cells carrying pGAL-CDC42Ala-118 were arrested as large, round, unbudded cells reminiscent of cdc42-1ts arrested cells. The different phenotype of the CDC42Ala-118 mutant versus the CDC42Val-12 and CDC42Leu-61 mutants was unexpected since the phenotypes of all three analogous ras mutants were similar to each other. This suggests that aspects of the biochemical properties of the Cdc42 protein differ from those of the Ras protein. The cdc42Ser-188 mutant gene was incapable of complementing the cdc42-1ts mutation and was recessive to both wild type and cdc42-1ts. In double-mutant alleles, the cdc42Ser-188 mutation was capable of suppressing the dominant lethality associated with the three putative GTP-binding and hydrolysis mutations, suggesting that isoprenylation is necessary for the activity of the wild-type and mutant proteins. PMID- 1904542 TI - Transcriptional regulation by Fos and Jun in vitro: interaction among multiple activator and regulatory domains. AB - The proteins encoded by the proto-oncogenes c-fos and c-jun (Fos and Jun, respectively) form a heterodimeric complex that regulates transcription by interacting with the DNA-regulatory element known as the activator protein 1 (AP 1) binding site. Fos and Jun are members of a family of related transcription factors that dimerize via a leucine zipper structure and interact with DNA through a bipartite domain formed between regions of each protein that are rich in basic amino acids. Here we have defined other domains in the Fos-Jun heterodimer that contribute to transcriptional function in vitro. Although DNA binding specificity is mediated by the leucine zipper and basic regions, Jun also contains a proline- and glutamine-rich region that functions as an ancillary DNA binding domain but does not contribute directly to transcriptional activation. Transcriptional stimulation in vitro was associated with two regions in Fos and a single N-terminal activation domain in Jun. These activator regions were capable of operating independently; however, they appear to function cooperatively in the heterodimeric complex. The activity of these domains was modulated by inhibitory regions in Fos and Jun that repressed transcription in vitro. In the context of the heterodimer, the Jun activation domain was the major contributor to transcriptional stimulation and the inhibitory regions in Fos were the major contributors to transcriptional repression in vitro. Potentially, the inhibitory domains could serve a regulatory function in vivo. Thus, transcriptional regulation by the Fos-Jun heterodimer results from a complex integration of multiple activator and regulatory domains. PMID- 1904543 TI - RAP1 is required for BAS1/BAS2- and GCN4-dependent transcription of the yeast HIS4 gene. AB - The major in vitro binding activity to the Saccharomyces cerevisiae HIS4 promoter is due to the RAP1 protein. In the absence of GCN4, BAS1, and BAS2, the RAP1 protein binds to the HIS4 promoter in vivo but cannot efficiently stimulate HIS4 transcription. RAP1, which binds adjacently to BAS2 on the HIS4 promoter, is required for BAS1/BAS2-dependent activation of HIS4 basal-level transcription. In addition, the RAP1-binding site overlaps with the single high-affinity HIS4 GCN4 binding site. Even though RAP1 and GCN4 bind competitively in vitro, RAP1 is required in vivo for (i) the normal steady-state levels of GCN4-dependent HIS4 transcription under nonstarvation conditions and (ii) the rapid increase in GCN4 dependent steady-state HIS4 mRNA levels following amino acid starvation. The presence of the RAP1-binding site in the HIS4 promoter causes a dramatic increase in the micrococcal nuclease sensitivity of two adjacent regions within HIS4 chromatin: one region contains the high-affinity GCN4-binding site, and the other region contains the BAS1- and BAS2-binding sites. These results suggest that RAP1 functions at HIS4 by increasing the accessibility of GCN4, BAS1, and BAS2 to their respective binding sites when these sites are present within chromatin. PMID- 1904544 TI - Ecdysterone receptor is a sequence-specific transcription factor involved in the developmental regulation of heat shock genes. AB - Purification of ecdysterone receptor from Drosophila melanogaster to apparent homogeneity is reported. Purified receptor binds specifically to several sequences in the promoters of the developmentally active hsp27 and hsp23 heat shock genes that were previously implied in ecdysterone regulation of the genes and that share limited homology among themselves and with mammalian steroid receptor binding sites. Some of these elements confer ecdysterone regulation on a basal promoter in transfected cells, acting in a synergistic fashion. Transcription in vitro of promoters containing such elements is stimulated up to 100-fold by added purified ecdysterone receptor, depending on receptor dosage and the number of elements present. Transcriptional enhancement requires sequence specific binding of receptor to template promoters which facilitates the formation of a preinitiation complex. Ecdysterone stimulates DNA binding of the receptor in vitro. PMID- 1904545 TI - Role of heat shock transcription factor in yeast metallothionein gene expression. AB - The induction of Saccharomyces cerevisiae metallothionein gene transcription by Cu and Ag is mediated by the ACE1 transcription factor. In an effort to detect additional stimuli and factors that regulate metallothionein gene transcription, we isolated a Cu-resistant suppressor mutant of an ACE1 deletion strain. Even in the absence of metals, the suppressor mutant exhibited high basal levels of metallothionein gene transcription that required upstream promoter sequences. The suppressor gene was cloned, and its predicted product was shown to correspond to yeast heat shock transcription factor with a single-amino-acid substitution in the DNA-binding domain. The mutant heat shock factor bound strongly to metallothionein gene upstream promoter sequences, whereas wild-type heat shock factor interacted weakly with the same region. Heat treatment led to a slight but reproducible induction of metallothionein gene expression in both wild-type and suppressor strains, and Cd induced transcription in the mutant strain. These studies provide evidence for multiple pathways of metallothionein gene transcriptional regulation in S. cerevisiae. PMID- 1904547 TI - Quantitative assessment of the genotoxicity of fecapentaenes. AB - Fecapentaenes are a group of fecal mutagens of microbial origin isolated from human stools. Fecapentaene-12 (F-12) and fecapentaene-14 (F-14), differing only in two carbon atoms in the side chain, are glyceryl ethers with a highly reactive chromophoric aliphatic side chain incorporating a conjugated pentaene moiety. Although these compounds are known for their genotoxicity, no test systems have been developed to precisely assess their relative genotoxicity. In this study F 12 and F-14 were assayed for their genotoxicity using the SOS Chromotest in which the induction of beta-galactosidase in E. coli PQ37 was used as a quantitative measure of biological activity. The activity obtained with F-12 and F-14 was compared with that of 4-nitroquinoline oxide (4-NQO) as the reference standard of a direct acting mutagen. While F-14 was almost as active as 4-NQO, F-12 was only about 25% as active as F-14, the higher analog. PMID- 1904546 TI - AAR1/TUP1 protein, with a structure similar to that of the beta subunit of G proteins, is required for a1-alpha 2 and alpha 2 repression in cell type control of Saccharomyces cerevisiae. AB - We have cloned a DNA fragment complementing the aar1 mutation defective in the a1 alpha 2 repression of the alpha 1 cistron and haploid-specific genes in Saccharomyces cerevisiae. Nucleotide sequence and mapping data indicated that the AAR1 gene is identical with TUP1, which is allelic to the SFL2, FLK1, CYC9, UMR7, AMM1, and AER2 genes, whose mutations are known to confer a variety of phenotypes, such as thymidine uptake, flocculation, insensitivity to glucose repression, a defect in UV-induced mutagenesis, and a defect in ARS plasmid maintenance. The TUP1/AER2 protein is known to have significant similarity with the beta subunits of G proteins in the C-terminal half, in two glutamine-rich domains in the N-terminal half, and in a central region rich in serine and threonine residues. Disruption of the chromosomal AAR1 gene in alpha and a/alpha cells conferred the nonmating phenotype, and the a/alpha diploids could not sporulate. The AAR1/TUP1 gene is transcribed into a 2.5-kb mRNA independently of the mating-type information of the cell. These observations and mRNA analysis of cell-type-specific genes indicated that the AAR1/TUP1 protein is also indispensable for a1-alpha 2 repression of RME1 and for alpha 2 repression of a specific genes. PMID- 1904548 TI - Mutagenicity of sumithion tested in Drosophila somatic and germ cells. AB - Sumithion, a broad-spectrum insecticide, was tested for its mutagenicity in the Drosophila wing-spot test and sex-linked recessive lethal test. Strains carrying the recessive mutant markers mwh and flr3 in their third chromosomes, expressed phenotypically as multiple trichomes or thickened and misshapen wing hairs in the adult wings, were used in the wing-spot test. Larvae transheterozygous for these markers were exposed to the insecticide in instant food and the sex-linked recessive lethal test was performed by the standard technique using the Basc strain. The compound is mutagenic in the wing primordial cells and induces recombination at high doses. Further, the frequency of induction of sex-linked recessive lethals is significant only at high treatment doses. PMID- 1904549 TI - Changes in the proliferation of human lymphocytes induced by several cytostatics and revealed by the premature chromosome condensation technique. AB - Premature chromosome condensation was induced by cell fusion in stimulated human lymphocytes treated with different cytostatics. Changes in the proportion of the cell-cycle stages were investigated after 72 h of culture. Although it has been reported that some agents which induce severe DNA damage accumulate cells in G2, our results have shown some differences in the modes of action of the different tested chemicals. These variations could be due to several factors like mechanisms of action of the drugs, sensitivity of lymphocyte subpopulations to the cytostatics, inter- and intra-individual variability in the response of donors. PMID- 1904550 TI - Further investigations on the clastogenicity of paracetamol and acetylsalicylic acid in vitro. AB - Paracetamol (PCM) and acetylsalicylic acid (ASA), both widely used analgesics, were tested for their clastogenicity in V79 cells in vitro. Rat liver S9 mix and primary rat hepatocytes (PRH) were used as external activation systems. ASA was found to be negative with and without activation system in concentrations up to 10(-2) M. In contrast PCM induced concentration-dependent chromosomal aberrations with and without activation system within the range of 3 x 10(-3) and 10(-2) M. The greatest effects were observed following continuous treatment with PRH activation and without external metabolization. Pulse treatments without external metabolization, with S9 mix and PRH were less effective. The clastogenic potency of PCM seems to be partly independent of metabolic activation. Although clastogenic effects in vitro were observed only in very high concentrations pharmacokinetic data and other published mutagenicity data indicate that there might be a risk for human use. Peak plasma levels of more than 10(-4) M have been reported (Forrest et al., 1982) and 2 groups of investigators (Kocisova et al., 1988; Hongslo et al., 1990) found PCM to be weakly clastogenic in human lymphocytes in vivo in the maximum human therapeutic dose range. PMID- 1904551 TI - A controlled trial of aerosolized ribavirin in infants receiving mechanical ventilation for severe respiratory syncytial virus infection. AB - BACKGROUND: Although the antiviral agent ribavirin improves the course of lower respiratory tract disease in spontaneously breathing infants with respiratory syncytial virus infection, it is not known whether ribavirin can benefit infants with severe respiratory syncytial virus disease who require mechanical ventilation. METHODS: We conducted a randomized, double-blind, placebo-controlled evaluation of ribavirin (20 mg per milliliter) administered continuously in aerosolized form to infants receiving mechanical ventilation for respiratory failure that was caused by documented respiratory syncytial virus infection. RESULTS: Of the 28 infants (mean [+/- SD] age, 1.4 +/- 1.7 months) enrolled, 7 had underlying diseases predisposing them to severe infection (mean age, 3.0 +/- 2.6 months), and 21 were previously normal (mean age, 0.8 +/- 0.9 month). Among the 14 infants who received ribavirin, the mean duration of mechanical ventilation was 4.9 days (as compared with 9.9 days among the 14 who received placebo; P = 0.01), and the mean length of supplemental oxygen use was 8.7 days (as compared with 13.5 days; P = 0.01). The mean length of the hospital stay was 13.3 days after treatment with ribavirin and 15.0 with placebo (P = 0.04). When only the 21 previously normal infants were considered, the mean length of the hospital stay was 9.0 days for the ribavirin recipients and 15.3 days for those who received placebo (P = 0.005). CONCLUSIONS: In infants who require mechanical ventilation because of severe respiratory syncytial virus infection, treatment with aerosolized ribavirin decreases the duration of mechanical ventilation, oxygen treatment, and the hospital stay. PMID- 1904552 TI - Medicine and health care in South Africa--five years later. PMID- 1904553 TI - Getting the best value for money in health care. PMID- 1904554 TI - New use of BCG for recombinant vaccines. AB - BCG, a live attenuated tubercle bacillus, is the most widely used vaccine in the world and is also a useful vaccine vehicle for delivering protective antigens of multiple pathogens. Extrachromosomal and integrative expression vectors carrying the regulatory sequences for major BCG heat-shock proteins have been developed to allow expression of foreign antigens in BCG. These recombinant BCG strains can elicit long-lasting humoral and cellular immune responses to foreign antigens in mice. PMID- 1904556 TI - [Lactose intolerance. I. Clinical aspects, diagnosis and therapy]. PMID- 1904555 TI - Differential regulation of rasGAP and neurofibromatosis gene product activities. AB - The ras-encoded p21ras proteins bind GTP very tightly, but catalyse hydrolysis to GDP very slowly. In humans, two genes encode proteins that stimulate this GTPase activity (GAP, or GTPase-activating proteins), one of relative molecular mass 120,000, referred to as p120-GAP, and another NF1-GAP, which is encoded by the neurofibromatosis type-1 gene. Both GAPs are widely expressed in mammalian tissues. Here we show that although they will both bind oncogenic mutants of p21ras, neither will stimulate their GTPase activity. NF1-GAP binds to the p21ras proteins up to 300 times more efficiently than p120-GAP. The two GAPs are inhibited to different extents by certain lipids: micromolar concentrations of arachidonate, phosphatidate and phosphatidylinositol-4,5-bisphosphate affect only NF1-GAP. This inhibition does not compete with p21ras, and lipid-inactivated NF1 GAP can still bind p21ras. We used the detergent dodecyl maltoside, which inhibits only NF1-GAP, to distinguish between the two activities in cell extracts and found both types present together in several mammalian cell lines. In contrast, GAP activity in extracts of Xenopus oocytes was not affected by dodecyl maltoside. By these criteria, the mammalian cells contain both GAP activities and the oocytes have only p120-like GAP activity. These results indicate that more than one GAP regulates p21ras in the same cell. PMID- 1904557 TI - [Lactose intolerance. II. Current biological viewpoints]. PMID- 1904558 TI - Inhibitory effect of oral sorbent on accumulation of albumin-bound indoxyl sulfate in serum of experimental uremic rats. AB - Serum indoxyl sulfate, which is markedly accumulated in uremic patients, cannot be removed efficiently by hemodialysis due to its albumin binding. To determine if oral adsorbent (AST-120) can decrease its serum concentration in uremic state, oral adsorbent was administered to experimental nephrectomized uremic rats. Uremic rats fed with oral adsorbent showed a significantly lower serum concentration of indoxyl sulfate compared to control uremic rats, even when serum concentrations of urea nitrogen and creatinine were not significantly decreased in the uremic rats fed with oral adsorbent. Indoxyl sulfate was detected only at a lower concentration in bile as compared with the serum of uremic rats. These results suggest that oral adsorbent adsorbs indole, a precursor of indoxyl sulfate, in the intestine and prevents the accumulation of indoxyl sulfate in uremic rats. PMID- 1904559 TI - Disruption of GnRH pulses by anti-GnRH serum and phentolamine obliterates pulsatile LH but not FSH secretion in ovariectomized rabbits. AB - It has been hypothesized that the secretion of gonadotropins, i.e. luteinizing hormone (LH) and follicle-stimulating hormone (FSH), is driven by a synchronized neural network ('pulse generator'). This network, regulated in part by alpha adrenergic activity, ultimately generates bursts of hypothalamic gonadotropin releasing hormone (GnRH) release. In this study, we used the push-pull (PP) perfusion technique in ovariectomized rabbits to investigate three aspects of the ('GnRH/gonadotropin pulse generator') hypothesis. The objectives were to determine: (1) if plasma LH and FSH pulses occur concomitantly with mediobasal hypothalamic (MBH-) GnRH pulses, (2) changes in the patterns of pulsatile LH and FSH secretion when pulsatile MBH GnRH signals are interrupted by either local immunoneutralization of GnRH or intravenous infusion of the alpha-adrenergic antagonist phentolamine (PHEN, 4 mg/kg BW), and (3) whether third cerebroventricular (3VT-) GnRH patterns reflect neuronal GnRH release from the MBH. We found that while both plasma LH and FSH patterns were pulsatile, MBH GnRH pulses were significantly coupled only with LH pulses (94% coincidence). Both the local immunoneutralization of MBH GnRH pulses and the PHEN-induced suppression of MBH GnRH pulses obliterated the pulsatile secretion of LH, but not FSH. Neither MBH GnRH nor plasma LH or plasma FSH pulses were concurrent with 3VT GnRH pulses. However, the PP perfusion of the 3VT appeared to alter the pulsatile release of MBH GnRH and pituitary LH. The results support the hypothesis that in the absence of ovarian signals, the 'pulse generator' is maintained by tonic alpha-adrenergic input and that a 'cellular unity' of MBH GnRH release (GnRH pulses) drives the gonadotrophs to secrete LH in pulses. In contrast, the pulsatile release of FSH appears to involve additional nonovarian regulatory events to those controlling LH secretion. PMID- 1904560 TI - Glucose affects the release of thyrotropin-releasing hormone from the rat hypothalamus. AB - We have attempted to elucidate the effect of glucose concentrations on the release of thyrotropin-releasing hormone (TRH), a brain neuropeptide possessing glucoregulatory function, from rat hypothalamic slices in vitro. Rat hypothalamic slices were preincubated for 60 min at 37 degrees C in Krebs-Ringer bicarbonate (KRB) buffer (pH 7.4) containing varying concentrations of glucose (10, 5, 2.5 and 1 mM), and then tissues were incubated in KRB buffer, followed by stimulation with 60 mM K+ or 1 mM ouabain. In addition, after inducing hypoglycemia by insulin administration in the rat, hypothalamic tissues were dissected out and preincubated in KRB buffer (10 mM glucose) and then incubated in fresh KRB buffer containing 1 mM ouabain. A decrease in the glucose concentration of incubation medium caused a dose-dependent decrease in both K(+)- and ouabain-stimulated TRH release from rat hypothalamic slices. Furthermore, the ouabain-stimulated TRH release from the hypothalamus of rats with insulin-induced hypoglycemia was significantly reduced (45% of control values; p less than 0.01). The present results indicate that in vitro and in vivo hypoglycemia resulted in a significant decrease in the release of TRH from the hypothalamus, suggesting that circulating glucose levels affect TRH release which, in turn, might be responsible for peripheral glucoregulation. PMID- 1904562 TI - DATATOP and clinical neuromythology IX. PMID- 1904561 TI - Structure-activity studies of neurotensin on muscular rigidity and tremors induced by 6-hydroxydopamine lesions in the posterolateral hypothalamus of the rat. AB - It has previously been reported that intracerebroventricular administration of neurotensin (30 micrograms) reduced muscular rigidity and tremors, induced by a neurochemical lesion with 6-hydroxydopamine in the posterolateral hypothalamus of rats. In the present study, the effects of two fragments (NT1-10 and NT8-13) and two analogues ([D-Tyr11]-NT and [Ala11]-NT) of neurotensin on the grasping time (index of muscle rigidity) and tremors in 6-hydroxydopamine-lesioned rats are reported. Intracerebroventricular administration with 120 micrograms of NT1-10 and [Ala11]-NT had no effect on the muscle rigidity and tremors induced by the neurochemical lesion. The administration of NT8-13 60 micrograms) significantly attenuated both behavioural responses. The analogue [D-Tyr11]-NT produced a much greater attenuation of the muscle rigidity and tremors. The dose of 1.8 micrograms of [D-Tyr11]-NT significantly reduced the grasping time, while the number of tremors was attenuated with the threshold dose of 0.9 micrograms. Together, these results suggest that the effects of neurotensin on muscle rigidity and tremors, induced by pretreatment with 6-hydroxydopamine injected into the posterolateral hypothalamus, were not caused by non-specific effects but largely depended on the carboxy terminal of the peptide. The tyrosine residue in position 11 of the molecule plays a critical role in the action of neurotensin, as shown with the high potency and duration of action of the analogue [D-Tyr11] NT. As previously suggested, the greater effect with [D-Tyr11]-NT may be due to greater resistance of the analogue to enzymatic degradation because of the incorporation of the D-Tyr amino acid, in position 11 of neurotensin. PMID- 1904563 TI - Soluble CD8 levels in the CSF and serum of patients with multiple sclerosis. AB - CD8 is a membrane glycoprotein of 34 kd on cytotoxic/suppressor T lymphocytes and is an endogenous ligand for MHC class I proteins on target cells. CD8 is released in a soluble form upon T-lymphocyte activation. In multiple sclerosis (MS), T lymphocytes exhibit decreased membrane expression of the CD8 molecule and defective suppressor function. We measured soluble CD8 (sCD8) levels in the CSF of patients with MS, other inflammatory neurologic diseases (INDs), and noninflammatory neurologic diseases (NINDs). sCD8 levels in the CSF of MS and IND patients were elevated compared with NIND patients. Patients with acute infections of the CNS showed the highest absolute values of sCD8, but the amount of sCD8 per CSF white blood cell was greatest in MS and NIND patients. We found no difference in serum sCD8 levels among the groups. In MS, the combination of increased CSF sCD8 levels and sCD8 per cell may reflect CD8 T-lymphocyte activation within the brain or immunodysregulation confined to the CNS. PMID- 1904564 TI - Selegiline (deprenyl) treatment and death of nigral neurons in Parkinson's disease. AB - We studied the effect of selegiline (deprenyl) treatment on the number of Lewy bodies and neuron counts in the substantia nigra in patients with Parkinson's disease (PD). The number of medial nigral neurons was greater and the number of Lewy bodies fewer in those PD patients who had been treated with selegiline in combination with levodopa as compared with patients who had received levodopa alone. This suggests that selegiline treatment may retard the death of nigral neurons, but alternative explanations, such as the reduction of levodopa dosage in selegiline-treated patients, are possible. PMID- 1904565 TI - The hazards of hypercaloric nutritional support in respiratory disease. AB - This case illustrates the dangers of hypercaloric feeding in a patient with limited respiratory reserve, in this instance secondary to heart-lung transplantation. The patient's postoperative course was complicated by repeated bouts of infection and/or rejection that resulted in intubation and ventilatory support. The excessive caloric and protein load given to the patient resulted in increased CO2 generation with subsequent inability to wean the patient off the ventilator. Recognition of the problem and appropriate decreases in substrate intake permitted extubation. PMID- 1904566 TI - Rapid development of vitamin K deficiency in an adolescent boy receiving total parenteral nutrition following bone marrow transplantation. AB - In this case report the development of a vitamin K deficiency in a neutropenic adolescent receiving parenteral nutrition following bone marrow transplantation is described. The parenteral nutrition solution did not provide vitamin K and the patient had been receiving oral antibiotics prior to and during use of the intravenous feeding. Oral intake was minimal. Standard adult oral and intravenous multivitamin preparations for use in individuals older than 11 years do not routinely contain this vitamin. The function of vitamin K and causes for development of a deficiency are reviewed. Recommended intakes and guidelines for supplementation are also discussed. PMID- 1904567 TI - Effect of maternal carbon dioxide inhalation on human fetal breathing movements in term and preterm labor. AB - Induced maternal hypercapnia is a potent stimulus to fetal breathing movements in nonlaboring pregnant women. To determine the effect of maternal CO2 administration on fetal breathing movements during spontaneous labor, 14 healthy pregnant volunteers at term and 34 in preterm labor were recruited. If fetal breathing movements were markedly decreased or absent, the subjects were administered a prepared gas mixture of 3% CO2 in air. In term labor and in true preterm labor, fetal breathing movements were markedly decreased and could not be induced by maternal hypercapnia. Among women with suspected preterm labor, initial absence of fetal breathing movements and failure to evoke this response by maternal hypercapnia predicted delivery within 48 hours with a sensitivity of 80% and specificity of 95.5%. Induced maternal hypercapnia fails to stimulate fetal breathing movements in true term and preterm labor and may assist in distinguishing between true and false preterm labor. PMID- 1904568 TI - Gonadotropin dynamics in women receiving immediate or delayed transdermal estradiol after oophorectomy. AB - A prospective study was performed in 24 premenopausal women to evaluate the gonadotropin dynamics of pharmacologic doses of transdermal estradiol-17 beta (E2) administered after bilateral oophorectomy. Patients were given 0.2-mg transdermal E2 patches for 2 weeks, followed by 0.1-mg patches for 4 weeks either immediately postoperatively (immediate estrogen replacement therapy [ERT]) or beginning 12-14 days after surgery (delayed ERT). Serum gonadotropins and E2 levels were measured serially, and postmenopausal symptoms were prospectively recorded. Administration of 0.2 mg transdermal E2 immediately after surgery suppressed the post-castration rise in gonadotropins for at least 4 days, but LH and FSH levels did increase to the menopausal range after 2 weeks despite continued therapy. Sustained circulating levels of E2 with transdermal E2 therapy were comparable to follicular phase values. Vasomotor symptoms were well controlled by 0.2 mg of transdermal E2 in the majority of patients during the clinical trial. There was no significant estrogen-related morbidity despite the large doses used. Two patients had skin irritation at the patch site causing discontinuation of therapy. These data suggest that large doses of transdermal E2 can suppress gonadotropin levels only for a brief interval. We were unable to demonstrate any long-term alteration in the hypothalamic-pituitary set point for sensitivity to exogenous E2. PMID- 1904569 TI - [Significance of the determination of gonadotropic pituitary hormones in different types of autonomic vascular dystonia]. AB - Measurements were made of the content of gonadotropic pituitary hormones (prolactin/PRL), luteinizing hormone (LH), follicle-stimulating hormone (FSH) and estradiol in 151 children aged 11 to 15 years. Of these, there were 58 healthy children (24 boys and 34 girls), 51 children (25 boys and 26 girls) with vegetovascular dystonia (VVD) of the vagotonic type and 42 children (22 boys and 20 girls) with VVD of the sympathotonic type. It has been established that in VVD children, alterations in the hypothalamus-pituitary-gonadal system agreed with the general biological reactions of the body, while deviations in the LH and FSH levels as well as in estradiol got stabilized by 13 to 15 years. A positive correlation has been revealed between the high blood PRL level and the high tone of the sympathetic nervous system. In view of this fact the blood PRL content can serve an early diagnostic test for recognizing hypersympathicotonia in VVD children. PMID- 1904570 TI - [Removal of the spleen and risk of the development of severe infections in children]. PMID- 1904571 TI - [Proposal for reform in the Norwegian health services]. PMID- 1904572 TI - [Crisis in the American health care system]. AB - According to Federal US law it is forbidden to reject patients or to curtail their care. The law may be seen as a democratic expression of the American people's wish to give all citizens access to the country's health services. Nevertheless it is estimated that millions of people in the USA wholly lack health insurance and very few of them succeed in paying their hospital bills. The problems of collection are so great that hospitals frequently refrain from even making the attempt. The law has a paradoxical effect; the health services are impoverished since no resources are set aside to cover the rising costs. PMID- 1904573 TI - Talking heads. PMID- 1904576 TI - Pharmacology of the nitrovasodilators. Antianginal, antihypertensive, and antiplatelet actions. AB - The nitrovasodilators, nitroglycerin and sodium nitroprusside, cause both arterial and venous smooth muscle dilation by the intracellular release of nitric oxide. Nitric oxide activates guanylate cyclase, resulting in an accumulation of cyclic GMP. The endogenous formation of nitric oxide results in vasodilatory activity similar to the nitrovasodilators. Nitroglycerin is commonly used in the treatment of angina pectoris because of its ability to decrease myocardial oxygen consumption. Most likely, this response occurs as a result of a reduction in preload, which can decrease arterial wall tension and improve coronary blood flow. This pharmacologic effect warrants the use of nitroglycerin in the treatment of myocardial ischemia or infarction, congestive heart failure, and hypertension. Sodium nitroprusside is effective in reducing arterial blood pressure in hypertensive crisis as a result of systemic vasodilation leading to a reduction in preload and afterload. Sodium nitroprusside is not as effective in the treatment of angina pectoris or in diminishing of myocardial ischemia because it does not preferentially improve blood flow to ischemic myocardium over nonischemic myocardium. Inhibition of platelet aggregation has been demonstrated with these drugs, but the clinical applications need further investigation. Nursing interventions for the patient on nitrovasodilator therapy include careful hemodynamic monitoring and drug infusion, along with elimination of physical and emotional stimuli that can aggravate the patient's underlying pathology. PMID- 1904574 TI - Marketing infection control. PMID- 1904575 TI - Nursing implications of immunosuppression in transplantation. AB - The numbers and survival rates of patients undergoing solid organ transplantation have increased over the past decade. The use of immunosuppressive drugs has contributed greatly to the success of transplantation. Drugs such as cyclosporine, steroids, azathioprine, ATG/ALG, OKT3, and new drugs under investigation such as FK506 are being used on a daily basis by nurses who care for organ transplant patients. This article reviews these medications and the implications for nurses administering these drugs. PMID- 1904577 TI - Current strategies for managing myelosuppression in patients with cancer. AB - Myelosuppression in patients with cancer is usually the result of tumor invasion of the bone marrow, cytotoxic chemotherapy, or radiation therapy, all of which suppress bone marrow function. Anemia, thrombocytopenia, and neutropenia are the three most clinically significant complications that result from bone marrow depression. Although anemia and thrombocytopenia can produce serious clinical problems, blood-component transfusions--despite having inherent problems of their own--usually are successful in correcting or minimizing these complications. Although neutropenia is manageable in most situations, it remains a serious problem that, at its worst, can progress to life-threatening septicemia. The longer neutrophil counts remain low, the more susceptible patients become to infection by endogenous and exogenous microbial flora. Accordingly, the oncology nurse increases the frequency of patient assessment and monitoring for infection. Control measures are introduced to minimize environmental contaminants. These measures attempt to reduce the incidence of opportunistic infections that frequently occur in patients with severe or prolonged neutropenia and for which antimicrobial therapy is indicated. Implementing specific infection-control interventions and thoroughly educating the patient and his/her family help to limit the clinical problems associated with myelosuppression for most patients. PMID- 1904578 TI - The spectrum and frequency of illness presenting to a pediatric emergency department. AB - Knowledge of the spectrum and relative frequencies of pediatric emergencies is an important factor in developing appropriate training curricula for physicians treating children in emergency departments. To provide these data, we reviewed the records for four one-week periods (January, April, July, and October) of a large pediatric emergency department to describe the population in terms of age, chief complaints, diagnoses, time of arrival, seasonal variation, and disposition. There were 3796 log entries. Complete information on all variables was obtained on 3784 patients. Age ranged from one day to 39 years, and the mean age was 6.0 +/- 6.15 years. One half of all emergency department visits were by children three years old or younger. On the other hand, 12% of visits were by adolescents (ages 13 to 18), and one in 25 visits was made by an adult (greater than 18 years old). The majority of chief complaints and final diagnoses were related to infection and trauma. More than half of the patients arrived on the evening shift, between 4 pm and 12 am. Eleven percent of the children seen on day and evening shifts and 13% from the night shift were admitted. From the analysis of our data we recommend expanded skills in the management of minor trauma for pediatric residents, an emphasis on management of infections for nonpediatric emergency specialists, and extensive training in both pediatric and adult trauma for physicians in pediatric emergency medicine fellowships. PMID- 1904579 TI - Utilization and clinical manifestations of human immunodeficiency virus type 1 infected children presenting to a pediatric emergency department. AB - A retrospective review was conducted of 22 human immunodeficiency virus type 1 (HIV-1)-infected children under 13 years of age presenting to an inner city pediatric emergency department to determine their clinical manifestations of disease and utilization of emergency department services. When compared with a population of 78 normal children, the infected children were more likely to present with cough, difficulty in breathing, and lethargy. Pneumonia, diarrhea, and dehydration were more common diagnoses in the infected children, who were more likely to be admitted, had more invasive procedures, and required more professional staff to provide care. There was no significant difference in the frequency of visits (visits/month of age) when comparing the two groups. As expected, the infected children presented with problems associated with pediatric HIV-1 infection. Our results suggest that HIV-1-infected children require an increased level of care in the emergency department and subsequent admission to the hospital. These children did not visit the emergency department more frequently than the controls. This may be the result of an active outpatient HIV clinic in our hospital, which is available to both scheduled and unscheduled patients. PMID- 1904580 TI - A one-year prospective ED cohort of pediatric burns: a proposal for standardizing scald burns. AB - During a 12-month period ending on 11/30/88, data were collected on 143 pediatric patients visiting a pediatric emergency department with burns. Sixty-four percent were males. Common causes of the burns included hot water (17%), hot food (23%), hot appliances (18%), and charcoal and grills (9%). Sixty-six percent of the burns took place at home. The hospitalization rate was 8%. A suggestion for standardizing scalds based on fluidity and function is proposed, since there is ambiguity regarding definition of a scald. PMID- 1904581 TI - The effect of taurine transport antagonists on cardiac taurine concentration and the incidence of sudden death syndrome in male broiler chickens. AB - Two experiments were conducted in which 540 day-old male broiler chickens were raised in heated battery brooders to 4 wk of age. Diets contained taurine antagonists to test effects on cardiac taurine content and the incidence of Sudden Death Syndrome (SDS). In Experiment 1 treatments during Weeks 2 to 4 were A) basal diet; B) basal diet supplemented with .25% guanidinoethyl sulfonate (GES) in Week 2 and 1.5% GES in Weeks 3 and 4; and C) basal diet supplemented with .5% GES in Weeks 2 to 4. The taurine content of heart was significantly reduced (P less than .05) with GES supplementation, but no effects on SDS mortality rates were noted. In Experiment 2 birds received diets containing 0. 2.5, or 5% beta-alanine. Supplementation with this compound decreased cardiac taurine concentration to extremely low levels (P less than .05). No significant effects on SDS mortality rates were noted. The results are interpreted as suggesting that taurine does not play a major role in the etiology of SDS. PMID- 1904583 TI - Bragg-Gray theory and ion chamber dosimetry for photon beams. AB - The validity of the Bragg-Gray cavity theory in photon radiation dosimetry for photon energies from 10 keV to 10 MeV has been investigated quantitatively in this paper. A crucial assumption for Bragg-Gray cavity theory to be valid is that the dose from photon interactions in the detector material is negligible. The ratio, Fair, of the absorbed dose resulting from photon interactions in an air cavity, DPA(air), to that in air under the condition of charged-particle equilibrium, DCPE(air), has been used as a parameter to determine if the air cavity can be classified as a Bragg-Gray cavity. Monte Carlo calculated results show that, for monoenergetic photon beams of energies above about 220 keV, the dose ratio, Fair, is smaller than 0.05 for an air cavity of 6 mm thickness and 6 mm diameter in vacuum. Furthermore, it is shown that the Burlin general cavity theory seriously overestimates the departure from Bragg-Gray behaviour. For clinical photon beams the dose ratio, Fair, is 0.29 for a 150 kVp beam and 0.27 for a 240 kVp beam compared to 0.006 for a 60 Co beam if the cavity is placed at a depth of 5 cm in water. This study confirms that typical air-filled ionization chambers cannot be considered to be Bragg-Gray cavities for low- and medium energy photon radiation. PMID- 1904582 TI - Biochemical and immunological characterization of major surface antigens of Sarcocystis muris and S. suicanis cyst merozoites. AB - Surface proteins of Sarcocystis cyst merozoites were labeled by biotinylation or radioiodination and identified on Western blots after sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The major labeled proteins of S. muris and S. suicanis have relative molecular masses of 31 and 33 kDa, respectively. Immunoblots performed with the 31-kDa protein and sera of experimentally infected mice or with monoclonal antibodies to S. muris revealed that this protein is immunogenic. Indirect fluorescent antibody tests (IFAT) executed using Sarcocystis cyst merozoites and polyclonal monospecific antibodies obtained from rabbits immunized with homogeneous major surface antigens gave additional evidence for the localization of the identified antigens in the pellicle. Analysis of S. muris and S. suicanis proteins by two-dimensional gel electrophoresis revealed multiple isoelectric forms. PMID- 1904584 TI - In situ neutron spectrometry to 60 MeV in a water phantom exposed to a cancer therapy beam. AB - In-air and in-phantom neutron spectra have been measured between 10 and 60 MeV for two field sizes on the Clatterbridge cyclotron by unfolding the response of a specially built NE213 scintillator. The in-phantom measurements show distinct spectral hardening with depth, which is reflected in changes in the spectrum averaged mean neutron energy. These findings are confirmed using Monte Carlo calculations. PMID- 1904585 TI - Observation of ultrasonic emission from edges of therapeutic x-ray beams. PMID- 1904586 TI - Investigation of heart rate and body temperature dynamics during a 14 days spaceflight experiment "COSMOS 2044". PMID- 1904587 TI - The monkey in space flight. PMID- 1904588 TI - Sonographic imaging of the thyroid in children. AB - High-resolution sonographic imaging of thyroid disorders in paediatrics has become an extremely accurate method and is being more frequently used. The need for scintigraphy has therefore dramatically decreased. The anatomy and sonographic morphology of the thyroid gland (normal findings, variants) in infants and children are presented, as are patterns of thyroid disorders and respective algorithms of diagnostic imaging. PMID- 1904589 TI - Surgery for endocrinological diseases and malformations in childhood. PMID- 1904590 TI - Pheochromocytoma in childhood. AB - Pheochromocytomas are uncommon tumors of childhood, accounting for 1% of hypertension cases in this age-group. Children have a high incidence of bilateral, multiple, or extra-adrenal tumors and a low incidence of malignancy. Alpha- and beta-blocking agents administered preoperatively have reduced complications markedly. Transabdominal resection is recommended because of the frequent extra-adrenal sites and multicentricity of the tumor in children. The mortality for removal of pheochromocytomas in childhood is currently less than 3%. PMID- 1904591 TI - Surgical treatment of ovarian tumors in childhood. AB - From 1971 to 1988, 45 girls aged 1 week to 17 years were treated for a total of 46 solid and cystic tumors of the ovaries. Pathohistological examination revealed epithelial tumors in eight cases, a tumor originating from the ovarian stroma in one case, germinal tumors in 17 cases, 15 functional ovarian cysts, and five paraovarian cysts. The stroma tumor and four of the 17 germinal tumors were malignant. Surgical treatment for solid tumors consisted generally of a unilateral salpingo-oophorectomy, but in operations for cystic tumors as well, vital ovarian tissue could only rarely be preserved. Functional ovarian cysts were excised if they were larger than 5 cm. Subsequent to excision of malignant tumors, chemotherapy with cisplatin, vincristine and bleomycin was performed. On follow-up, all patients with benign lesions were well. One of the girls with malignancies died and another is undergoing chemotherapy for tumor recurrence in the contralateral ovary. PMID- 1904592 TI - Recent developments in the management of neuroblastoma. AB - Neuroblastoma was first described in 1864 by Virchow. For the next 100 years, the primary approach to these patients was predominantly surgical resection. With the advent of multimodal adjuvant treatments using chemotherapy and irradiation in the 1950s and 1960s, coordination of multispecialty therapeutic interventions became important. By the late 1970s, effective neoadjuvant chemotherapeutic regimens enabled some inoperable tumors to be completely removed at the time of "second look" procedures. In the 1980s, advances in tumor biology and imaging gave new insight and novel prognostic indicators which helped determine the course of therapy. In the 1990s, treating poor risk patients with extremely high dose chemotherapy, irradiation, and allogeneic or autologous bone marrow rescue with or without surgical resection may finally improve the survival of these children. PMID- 1904593 TI - Surgical aspects of diseases of the thyroid gland in childhood. AB - The treatment of juvenile struma is the domain of the pediatrician, and operations are rarely necessary, even in struma-endemic regions. An absolute indication for surgery is diagnosed or suspected struma maligna: relative indications are hyperthyroidism and euthyroid goiter. The operative procedure in benign thyroid diseases is based on the pathogenesis: a tissue-saving technique is mandatory to prevent postoperative hypothyroidism. Therapeutic strategy in malignant diseases, i.e., the radicality of surgical and postoperative management, depends, as in adults, on the prognostic relevance of variable parameters. PMID- 1904594 TI - Surgery for benign and malignant diseases of the thyroid gland in childhood. AB - From 1970 to 1986, 51 children and adolescents aged 5-18 years were operated on for diseases of the thyroid gland, among them 42 with benign diseases (juvenile goiter 21, adenoma 17, Graves' disease 3, Hashimoto's thyroiditis 1) and nine with malignancies (papillary carcinoma 4, follicular carcinoma 3, medullary carcinoma 1, anaplastic carcinoma 1). In benign entities, females were three times as often affected as males, whereas both sexes were equally affected in malignancies. Positive family histories were found in 23.3% of the children with adenomas in 71.4% of the children with juvenile goiters. Subtotal strumectomy was carried out in 30 instances and enucleation in 12. Iodized salt and L-thyroxine were given postoperatively as recurrence prophylaxis. Recurrence was seen in two children (4.8%) who had no recurrence prophylaxis. Symptoms in children with malignancies were palpable cervical lymph nodes and solitary nodes in the thyroid gland. Total thyroidectomy was done in all instances, followed by radio-iodine treatment in eight cases and cobalt 60 irradiation in one case. Two children died, of diffuse metastases and irradiation fibrosis of the lung respectively. The peculiarities of diseases of the thyroid gland in childhood that require surgery are discussed. PMID- 1904595 TI - Indications, surgical treatment and after-care in juvenile hyperthyroidism. AB - Between 1974 and 1985, 12 children and adolescents aged 10-18 years were operated on for immunogenic hyperthyroidism resistant to medical treatment. Bilateral, subtotal strumectomies were carried out, leaving a remnant of 2-3 g of thyroid tissue in place. There were no immediate postoperative complications. Hyperthyroidism recurred in two instances. During the same time, 26 children and adolescents up to 18 years of age underwent surgery for autonomous adenoma. Enucleation is the method of choice in adenoma, but is not always possible. PMID- 1904596 TI - Late results of thyroid surgery for hyperthyroidism performed in childhood. AB - The authors report on the complex follow-up of 60 patients operated on for hyperthyroidism in childhood, on average 13.7 years after surgery. In 16.7% of the patients manifest hypothyroidism, in 45% subclinical hypothyroidism was found; 30% of the patients were euthyroid, and manifest hyperthyroidism recurred in 8.3%. Autonomous adenomas were enucleated in two children and three young adults. Severe disorders in thyroid function developed especially after the surgery of diffuse toxic goiters accompanied by ophthalmopathy. The disorders of humoral and cellular immunity were detected most frequently in recurrent manifest hyperthyroidism. There was no case where ophthalmopathy progressed after the operation. In the offspring of the operated patients the incidence of hyperthyroidism was not increased in childhood. The authors call attention to the importance of postoperative follow-up and hormone treatment. PMID- 1904597 TI - Late prognosis of childhood and juvenile thyroid carcinomas. AB - The authors report on the biological properties and late prognosis of 16 children and juvenile patients operated on during the past 24 years for thyroid tumour who underwent regular followup. The clinical and morphological characteristics of the carcinomas are described, together with the late immune response of the patients undergoing complex treatment. The study is also concerned with the characteristics of the DNA content of the tumorous cell nuclei, the pregnancy success rate of the operated patients and the thyroid function of the children born. PMID- 1904598 TI - Parathyroid surgery in children. AB - Parathyroid surgery in children is uncommon. Spontaneously occurring cases of hyperparathyroidism are almost always due to single-gland disease: however, on exploration all four parathyroid glands should be identified. Most of the other instances in which the surgeon needs to perform a parathyroidectomy on an infant or a child will be situations were multiple-gland disease is the rule rather than the exception. Therefore, the surgeon must have in his mind a well developed logical approach to the management of children with parathyroid disorders on the basis of multiple glandular disease. We believe that the technique of parathyroid autotransplantation very satisfactorily addresses the surgical needs of children with familial hyperparathyroid states, including the multiple endocrine neoplasias. We believe that it is mandatory treatment in patients presenting with neonatal primary hyperparathyroidism and is also the procedure of choice in children with secondary and tertiary hyperparathyroidism. The workup and diagnosis of parathyroid disorders should be familiar to the surgeon who undertakes neck exploration on children, and the entity of familial hypocalciuric hypercalcemia should be looked for, as these patients have a strong likelihood of not benefiting from parathyroidectomy. PMID- 1904599 TI - Current status of pancreatectomy for persistent idiopathic neonatal hypoglycemia due to islet cell dysplasia. AB - A series of 18 children suffering from persistent idiopathic neonatal hypoglycemia (PINH) is reported. Medical and surgical managements are described in detail. All patients subjected to surgery had failed medical treatment. These patients were divided into two groups: 1) 85% pancreatectomy leaving the uncinate process in situ, and 2) 95% pancreatectomy leaving a small rim of pancreatic tissue along the duodenum and the common bile duct. The spleen was preserved in all cases. Two out of 5 children of group 1 required further resection of the pancreas for persistent hypoglycemia and were converted to 95% pancreatectomy. Since 1981 95% pancreatectomy was exclusively employed. Only one patient required insulin for 3 weeks postoperatively. Histopathology and immunohistochemistry revealed islet cell dysplasia and islet cell nuclear hypertrophy in the majority of cases, 35% of the patients had focal adenomatosis. Better control of hypoglycemia is achieved by primary 95% pancreatectomy and, thus, 95% pancreatectomy is recommended as the initial procedure in the treatment of PINH. PMID- 1904600 TI - Surgery for nesidioblastosis--indications, treatment and results. AB - Nesidioblastosis is a life-threatening form of hypoglycemia that starts during the neonatal period in most cases and is caused by hyperinsulinism. Its diagnostic criteria are an extremely high demand for carbohydrates (more than 15 g/kg/day), an inadequately high plasma insulin level, and an inhibited production of ketone bodies. This acute, life-threatening hypoglycemia requires immediate intensive-care treatment. The most important aim of continuous therapy is the prevention of irreversible brain damage. This cannot be reliably avoided by conservative treatment (increased carbohydrate supply, diazoxide administration). Therefore, surgical treatment consisting in subtotal pancreatectomy is becoming increasingly important. The reduction of hormone-producing tissue resolves hyperinsulinism and apparently enables the onset of physiological regulatory mechanisms. Surgical strategy and results in 12 children who underwent surgery for nesidioblastosis are described. PMID- 1904601 TI - Surgical treatment of nesidioblastosis in childhood. AB - A review of the literature on the surgical treatment of nesidioblastosis in childhood was made to answer the following questions: age at operation, surgical procedure, pathohistological findings, incidence of recurrence and its treatment, as well as mortality. Primary subtotal pancreatectomy appears to be the method of choice. It should be performed as early as possible following exact diagnosis. Total pancreatectomy is reserved for treatment of a recurrence. PMID- 1904602 TI - Total pancreatectomy in a case of nesidioblastosis due to persisting hyperinsulinism following subtotal pancreatectomy. AB - Hypoglycemia with hyperinsulinism persisted in a newborn weighing 6410 g despite treatment with high doses of diazoxide and glucagon, as well as infusions of glucose and somatostatin. A subtotal pancreatectomy was performed after nesidioblastosis had been diagnosed on the basis of the laboratory findings. Due to the persistence of therapy-resistant hypoglycemia, a total pancreatectomy preserving the duodenum and the bile duct was done 6 weeks later. With insulin and pancreatic enzyme substitution the now 6-year, 9-month-old child has shown normal, age, appropriate development. PMID- 1904603 TI - Pancreatic head tumor in a child. AB - A 13-year-old girl with pancreatic head tumor required a pancreatoduodenectomy (Whipple procedure). Pathohistological examination disclosed a pancreatic apudoma. The characteristics of this very rare tumor, its symptoms and treatment are described. PMID- 1904604 TI - [Comments on the responses to my Psyche contribution "Very frequent long-term analysis and psychoanalytic practice. Utopia and reality" by W. Schubart, H.-G. Metzger and C. Frank (Psyche 11/1990)]. PMID- 1904605 TI - Interview of the editorial office. PMID- 1904606 TI - Combined brachytherapy and external beam radiotherapy. PMID- 1904608 TI - Combined brachytherapy and external radiotherapy for carcinoma of the prostate. Experience and results. PMID- 1904607 TI - Combined irradiation treatment in breast cancer. PMID- 1904609 TI - Combined external radiotherapy and brachytherapy of brain tumors: a review. PMID- 1904610 TI - Combined external radiotherapy and intracavitary radiotherapy in esophageal carcinoma. PMID- 1904611 TI - Combined external radiotherapy and Syed's curietherapy in the treatment of carcinoma of the cervix. PMID- 1904612 TI - Combined ERT and IRT in carcinoma of the vulva. PMID- 1904614 TI - Combined treatment in pancreatic carcinoma: review of literature. PMID- 1904613 TI - Combined external beam irradiation and interstitial radiotherapy of T1-T2 cancers of the mobile tongue and floor of mouth. PMID- 1904615 TI - Combined brachytherapy and external beam radiation in the treatment of anal and rectal carcinoma. PMID- 1904616 TI - Combined brachytherapy and external beam radiation in soft tissue sarcomas. PMID- 1904617 TI - Indications and results of combined external beam radiation and interstitial radiotherapy in the treatment of carcinoma of the oropharynx. PMID- 1904618 TI - Role of lipoxygenase in xenobiotic metabolism: sulfoxidation of thiobenzamide by purified soybean lipoxygenase. AB - Earlier this laboratory recognized lipoxygenase catalyzed reactions as a novel pathway for xenobiotic metabolism. To further explore the spectrum of reactions catalyzed by lipoxygenase, sulfoxidation of thiobenzamide was studied. Purified soybean lipoxygenase was found to oxidize thiobenzamide to thiobenzamide sulfoxide in the presence of linoleic acid at a rate of 241 nmoles/min/nmole enzyme. The reaction was dependent upon enzyme, pH, thiobenzamide and linoleic acid concentration. Other polyunsaturated fatty acids namely arachidonic acid, cis, 11, 14-eicosadienoic acid and linolenic acid also supported the sulfoxidation reaction. Nordihydroguaiaretic acid and phenidone, the classical inhibitors of lipoxygenase, significantly blocked the sulfoxidation of thiobenzamide. PMID- 1904619 TI - Activation of bovine peripheral blood macrophages in Theileria sergenti-infected calves. AB - Macrophage activation in Theileria sergenti-infected calves was studied by testing the production of oxygen metabolites in macrophages following specific and non-specific stimulation with T sergenti merozoites or zymosan, respectively. Six calves were inoculated with merozoites and three calves with sporozoites. All showed significant macrophage activation within one month after inoculation (P less than 0.05). Activation of macrophages appeared earlier than parasitaemia or the peak of antibody titre against T sergenti. The highest chemiluminescence response, indicative of macrophage activation, was observed when the merozoites were opsonised with immune sera. PMID- 1904620 TI - [Multicenter study comparing efficacy and tolerance of moclobemide and fluvoxamine in hospitalized and ambulatory patients with severe depressive episodes]. AB - In a double blind study performed in psychiatric clinics the efficacy and tolerability of the new antidepressant Moclobemide was compared. Moclobemide belongs to a new class of substances called RIMA (Reversible Inhibitor of the monoamine oxidase type A). 61 patients with major depression (according to DSM III) were either treated with Moclobemide or Fluvoxamine, a selective reuptake inhibitor of 5-HT. The latter belongs to a class of antidepressants known for their better tolerability compared to tricyclic antidepressants. Moclobemide was as effective as Fluvoxamine but much better tolerated as shown by a lower incidence of side effects such as gastrointestinal problems or headache. PMID- 1904621 TI - [The effect of CO2 laser radiation on the morphological changes of mucocutaneous wound healing in oral surgery. A histo-enzymologic and ultrastructural study]. AB - The tissular effects of CO2 laser were compared with those of conventional surgery on cutaneo-mucous biopsies performed during stomatologic surgery. Two hours after the incision, a cellular necrosis was seen and vessels were obliterated by a turgescent endothelium, explaining the bloodless character of wounds with laser. After 24 hours, though vasculo-exsudative end inflammatory reaction were weak, an intense functional stimulation of fibroblasts was obvious (turgescent cells with numerous organelles). At the 4th day, this fibroblastic hyperactivity was always persistant with an abundant microfibrillar secretion. Myofibroblasts, usually present during cicatrization after scalpel, were lacking in our material; this constatation should explain the relative slowness of cicatrization after CO2 laser. PMID- 1904622 TI - [Recklinghausen's disease]. AB - The authors report a case of Von Recklinghausen's disease of hereditary origin presenting with maxillo-faciale manifestations. They also discuss the therapeutic indications and consider the psycho-social problems associated with facial dysmorphism. PMID- 1904623 TI - [Aponeurosis plantaris--phylogenetic development]. AB - The plantar aponeurosis is differentiated in its most primitive form in Marsupialia, where it is formed by a single connective tissue strip, a continuation of the tendon of the m. plantaris. The tendon is usually not fixed to the calacaneal tuberosity. The lateral tract (fibular) of the plantar aponeurosis takes a distal course and forms processes for the first to fifth toe. (The number of inserting strips is different and variable in different species of marsupials). A separate medial (tibial) strip of the aponeurosis is lacking. 2. In Insectivora the plantar aponeurosis is differentiated similarly as in marsupials. Again the medial (tibial) strip of the aponeurosis is absent and the tendon of the m. plantaris is more firmly fixed to the calcaneus. Scandentia (Tupalia) have a two-layer aponeurosis. The fibular (lateral) layer is in continuation of the tendon of the m. plantaris, the medial (tibial) layer starts at the calcaneal tuberosity. The plantar aponeurosis of Tupalia does not yet form two separable tracts, however, the forming layers of the aponeurosis indicate the future separation of the uniform connective tissue plate. 3. In prosimians and simians a separate medial (tibial) tract develops which is independent on the tendon of the m. plantaris, and in anthropoids and humans gradually the planta predominates. PMID- 1904624 TI - Subcellular distribution of monoclonal antibody defined epitopes on immunodominant Mycobacterium tuberculosis proteins in the 30-kDa region: identification and localization of 29/33-kDa doublet proteins on mycobacterial cell wall. AB - Two different groups of monoclonal antibodies (MAbs) directed to different epitopes on 30-kDa region proteins of Mycobacterium tuberculosis were isolated; MAbs 5F9, 5D5 and 5D2 reacted with a single 33-kDa protein band, whereas MAb 3A8 reacted with a distinct 29/33-kDa doublet when analysed by immunoblotting. The present paper describes the distribution of MAbs defined epitopes in the 29-33 kDa region proteins in well-characterized subcellular fractions: cytosol, plasma membrane, cell wall as well as culture filtrate of M. tuberculosis. MAbs 5F9, 5D5 and 5D2 reactive epitopes were found in cytosol, whereas 3A8 epitope is distributed in all cellular compartments of the mycobacterium as well as in the culture filtrate. Localization of these epitopes by indirect immunofluorescence and immunogold-labelling demonstrated that only 3A8 epitope is present on the cell surface of the mycobacterium. Both immunoblotting and ELISA showed that only MAb 3A8, and not 5F9, 5D5 and 5D2, reacted with secreted BCG 85 antigen complex of Mycobacterium bovis BCG. Furthermore, using an MAb 3A8-coupled affinity column, we purified antigen 3A8 from the cytosol fraction of M. tuberculosis. All these MAbs reacted with antigen 3A8 with varying degrees of intensity, thus suggesting that they are directed to a single protein. Absence of 5F9, 5D5 and 5D2 epitopes in the cell wall, culture filtrate and to a single protein. Absence of 5F9, 5D5 and 5D2 epitopes in the cell wall, culture filtrate and BCG-85 complex suggests that these epitopes might have been lost during the processing of the same 33-kDa protein on its way out from cytosol to the cell wall or when the protein is secreted out into the culture filtrate. Our results demonstrate, for the first time, direct evidence of the presence of a 30-kDa region protein not only in secreted antigens but also in the cell wall and on the cell surface of the mycobacterium. PMID- 1904625 TI - Continuous intestinal dialysis for uraemia by intermittent oral intake of non absorbable solutions. An experimental study. AB - A new approach to intestinal dialysis was investigated in a normal person and in a patient with chronic uraemia and a renal creatinine clearance of 10 ml/min. Both subjects drank 1-1.5 l non-absorbable solutions of polyethylene glycol or mannitol every fourth hour. The solutions stayed in the intestines for about four hours in the normal person and for 1.5 to 3 hours in the patient. The patient's intestinal clearances were 6-10.4 ml/min for creatinine, 4 ml/min for uric acid and 10.7-15.4 ml/min for phosphate, which compares favourably to those from 12 hours weekly haemodialysis. Continuous intestinal dialysis was well tolerated and the results indicate that this might be a useful way of treating uraemia if conventional methods are unavailable. PMID- 1904626 TI - Mediation of the attachment or fusion step in vesicular transport by the GTP binding Ypt1 protein. AB - The function of the guanosine triphosphate (GTP)-binding protein Ypt1 in regulating vesicular traffic was studied in a cell-free system that reconstitutes transport from the endoplasmic reticulum to the Golgi. Blocking the Ypt1 protein activity resulted in accumulation of vesicles that act as an intermediate passing between the two compartments. The Ypt1 protein was found on the outer side of these vesicles. The transport process is completed by fusion of these vesicles with the acceptor compartment, and Ypt1 protein activity was needed for this step. Thus, a specific GTP-binding protein is required for either attachment or fusion (or both) of secretory vesicles with the acceptor compartment during protein secretion. PMID- 1904627 TI - Network rigidity and metabolic engineering in metabolite overproduction. AB - In order to enhance the yield and productivity of metabolite production, researchers have focused almost exclusively on enzyme amplification or other modifications of the product pathway. However, overproduction of many metabolites requires significant redirection of flux distributions in the primary metabolism, which may not readily occur following product deregulation because metabolic pathways have evolved to exhibit control architectures that resist flux alterations at branch points. This problem can be addressed through the use of some general concepts of metabolic rigidity, which include a means for identifying and removing rigid branch points within an experimental framework. PMID- 1904628 TI - Selective elimination of HIV-1-infected cells with an interleukin-2 receptor specific cytotoxin. AB - Infection by human immunodeficiency virus type 1 (HIV-1) is associated with cellular activation and expression of the interleukin-2 (IL-2) receptor. A genetically engineered fusion toxin, DAB486 IL-2, that contains the enzymatic site and translocation domain of diphtheria toxin and the receptor binding domain of IL-2 specifically kills cells that express high-affinity IL-2 receptors. This toxin selectively eliminated the HIV-1-infected cells from mixed cultures of infected and uninfected cells and inhibited production of viral proteins and infectious virus. Thus, cellular activation antigens present a target for early antiviral intervention. PMID- 1904629 TI - Fibrinolytic therapy of deep vein thrombosis with continuous intravenous infusion of a recombinant tissue plasminogen activator. AB - Recombinant human rt-PA was administered to 22 patients with deep vein thrombosis at a dosage of 30 to 120 mg/day (0.5 to 1.76 mg/kg body weight/24 hr) over 2 to 10 days. rt-PA induced phlebographically documented substantial recanalization in 18 of 21 patients. The lowest dose of 0.5 mg/kg/24 hr tested here was thrombolytically effective, whereas a dose of 0.95 mg/kg/24 hours and more led to hemorrhagic complications and premature discontinuation of therapy in four of six patients. Blood clotting analysis did not reveal any substantial decrease in fibrinogen concentrations, whereas the euglobulin clot lysis time and thromboelastography demonstrated a systemic fibrinolytic effect. Therapy with rt PA can thus be considered as an alternative and effective method of therapy in treatment of deep vein thrombosis. The results of this study show that even a dosage of lower than 0.5 mg/kg/24 hr might prove to be effective. Further studies would be required to show whether the fibrin specificity of rt-PA leads to a superiority of this fibrinolytic substance over the conventional thrombolytic agents, streptokinase and urokinase. PMID- 1904630 TI - CAIII a marker for early myogenesis: analysis of expression in cultured myogenic cells. AB - Carbonic anhydrase III (CAIII) is an abundant muscle protein characteristic of adult type-1, slow-twitch, muscle fibers. We demonstrate that CAIII is not confined to mature muscle but is also expressed in cultured myogenic cells that were originally derived from adult and fetal limb muscle (G8 and C2C12) and by azacytidine treatment of 10T1/2 fibroblasts (23A2). Transcripts may accumulate in these cells to levels that correspond to 6.5% of that found in mature muscle. CAIII is expressed in mononucleate myoblasts and is abundant in those that preferentially fuse to form myotubes, and these findings contrast with those for many other muscle genes whose transcripts only accumulate on or after terminal differentiation. Preliminary promoter-function assays by transfection shows that 2.8 kb of sequence flanking the 5' end of the human CAIII gene efficiently promotes transcription of the bacterial chloramphenicol acetyltransferase gene in myogenic cells. However, none of the sequences within this region are sufficient to confer muscle-specific expression. Removal of sequences 5' to -715 bp leads to a major loss of transcriptional activity of the CAIII promoter. These results imply that the proximal CAIII promoter, which includes a putative CArG box and four potential MyoD binding sites, is not adequate for either myoblast-specific or maximal transcription. PMID- 1904631 TI - Instability of immunoglobulin genes in S107 cell line. AB - Somatic mutation occurs frequently in rearranged and expressed immunoglobulin variable region genes in vivo. In contrast, V region hypermutation seldom occurs in antibody-forming cells in culture. The S107 mouse myeloma cell line is one of the few cell lines that has been observed to generate V region mutations frequently and spontaneously in vitro. Detailed examination reveals that both the S107 tumor and the cell line derived from it contain and express a duplicated heavy-chain gene. In culture, only one of the two heavy-chain genes undergoes both V and C region mutation, and variants with complex phenotypes and genotypes arise as a result of mutation and segregation of these duplicated genes. PMID- 1904632 TI - Schistosomiasis of the spinal cord--underdiagnosed in South Africa. PMID- 1904633 TI - Cerebral oedema with coning in diabetic keto-acidosis. Report of 2 survivors. AB - Two children presented with a first episode of diabetic ketoacidosis. Initially both patients made a good clinical and biochemical recovery, but suddenly developed neurological signs consistent with a diagnosis of tentorial herniation. Cranial computed tomography showed signs of cerebral oedema in both cases with evidence of uncal and tentorial herniation in 1 patient, which resolved after the appropriate treatment. The excellent neurological outcome emphasises the need for early recognition and treatment of sudden onset brain oedema in diabetic keto acidosis. PMID- 1904634 TI - Past, present, and future of nutritional support. AB - Early rudimentary attempts to provide adequate nutrition by mouth, intestinal tube, and vein in order to reduce morbidity and mortality have advanced to strategies designed to maintain the integrity of the body cell mass. Technology has progressed geometrically in recent years with the development of organ specific enteral and parenteral substrate mixtures; sophisticated assessment, delivery, and monitoring systems; and improved safety and efficacy. Nutritional support is rapidly evolving into the practice of clinical biochemistry, in which nutrient substrates will be formulated to enhance or maximize cellular function, not only under normal conditions, but under a wide variety of pathophysiologic conditions. PMID- 1904635 TI - Current strategies in surgical nutrition. PMID- 1904636 TI - Nutritional assessment and indications for nutritional support. AB - The goal of nutritional assessment is to identify prospectively all those patients who would develop a nutrition-related complication. In practical terms, there is no single test capable of achieving this goal. At present, the best method of nutritional assessment is an organized step-by-step multifactorial approach. This involves assessment of the primary illness, the patient history, and the prognosis. A nutritional status examination is done, and the current intake is compared with the nutritional goals. A decision is then made whether to force feed. If forced feeding is initiated, the effectiveness of the therapy must be monitored frequently until the patient recovers and is able to be sustained by volitional oral intake. PMID- 1904637 TI - Amino acids in surgical nutrition. Principles and practice. AB - Amino acids will always be an integral part of nutritional support in all patients. The use of specific amino acids in pharmacologic doses may be beneficial to certain critically ill patients, indicating that such compounds are conditionally essential. As our knowledge of the altered regulation of amino acid metabolism in surgical patients improves, the design of more effective feeding regimens will follow. The goal should be to provide the best nutrition to all patients at all times. PMID- 1904638 TI - Total parenteral nutrition in the pediatric patient. AB - Over the past 50 years, tremendous advances have been made in the management of children who cannot receive enteral nutrition. Challenges for the future include devising techniques to decrease catheter sepsis, particularly in children with a short bowel, who have a disproportionate number of septic episodes, possibly related to bacterial translocation. The delineation of risk factors for cholestasis associated with total parenteral nutrition and refinement of administration of such nutrition in premature neonates to decrease the incidence of this complication, as well as the morbidity of osteopenia, will extend our ability to help these children. PMID- 1904639 TI - Perioperative nutritional support. AB - In selected malnourished patients, perioperative nutritional support can decrease the morbidity and mortality rates associated with major surgical procedures. Preoperative nutritional support should be delivered via the gastrointestinal tract whenever feasible, generally in the form of enteral diets, which can be given via a feeding tube or as a dietary supplement. Patients with a functional gut who cannot eat because of anorexia or upper gastrointestinal tract obstruction are candidates for preoperative tube feedings. Total parenteral nutrition should be the mainstay of nutritional support when the gastrointestinal tract cannot be used adequately. An improvement in nutritional indices (e.g., serum transferrin, lymphocyte count) may be associated with decreased perioperative morbidity, although the strength of this relation is not clear. In the absence of improvement in such indices, the duration of nutritional support required to decrease operative morbidity is unknown. Postoperatively, enteral tube feedings (delivered via a nasojejunal tube or feeding jejunostomy) should be provided to all preoperatively malnourished patients with a functional gastrointestinal tract who are unable to consume adequate calories orally. Postoperative TPN should be reserved for malnourished patients with a nonfunctional gut or for patients who develop a postoperative complication that precludes enteral feeding. Current nutritional formulas have often neglected the metabolic and nutritional requirements of the intestinal tract. In the future, the combined use of specific nutrients and growth factors may improve nutritional rehabilitation in catabolic patients. PMID- 1904640 TI - Nutritional consequences of major gastrointestinal surgery. Patient outcome and starvation. AB - Advances in major gastrointestinal surgery and the existence of a significant number of high-risk patients necessitate a detailed knowledge of the metabolic response to surgery and the need for adjunctive nutritional therapy. Such surgery has the potential to cause significant nutritional consequences affecting patient outcome. Often, patients present malnourished preoperatively because of their chronic gastrointestinal disease, advanced age, or comorbidity. Still others are at great risk for developing malnutrition postoperatively secondary to the hypercatabolism of prolonged illness or postoperative complications. In addition, the surgical alterations of the gastrointestinal tract might disrupt normal function sufficiently to result in chronic nutritional deficiencies. Because starvation is no longer an acceptable condition, these concerns need to be recognized prior to surgery, and if indicated, nutritional support must be initiated preoperatively. Placement of feeding jejunostomy catheters for early enteral support should be considered for all high-risk patients. Equally important, surgeons should maintain a watch for future nutritional innovations that will improve their ability to meet patients' nutritional requirements. PMID- 1904641 TI - Nutritional support of patients with cancer of the gastrointestinal tract. AB - Malnutrition is extremely common in patients with malignant disease. Whereas the causes are multifactorial, the predominant factor is the imbalance between nutrient intake and host nutrient requirements. Furthermore, the evidence suggests that cachexia is related to abnormal changes in host intermediary metabolism induced by host-tumor interactions, and endogenous peptides such as TNF may be important mediators. The role of nutritional therapy in cancer patients remains to be defined. Clearly, patients with severe malnutrition benefit from nutritional intervention. However, the benefit of nutritional therapy in less severe cases of malnutrition as an adjuvant to oncologic therapy has yet to be established. PMID- 1904642 TI - Nutritional support in the injured patient. AB - After injury, the stress reaction causes hypermetabolism and consequent depletion of the body's tissues. Nutritional support should be begun early and should be given by the enteral route if possible. New developments may allow the modulation of the stress and immune responses by nutrient therapy. PMID- 1904643 TI - Nutrition and metabolism in sepsis and multisystem organ failure. AB - Sepsis and organ failure produce profound metabolic changes that contribute to hepatic and musculoskeletal failure. When multiple organ failure develops, the mortality rate is high, and therapy is unlikely to be effective unless the causative process (e.g., infection, low cardiac output) can be eliminated. Thus, the prevention of multiple organ failure and the prevention or early treatment of infection are paramount. Organ and nutritional support to prevent complications is necessary. The gastrointestinal tract should be used for nutrition whenever possible with a blenderized regular diet with fiber, glutamine, and short-chain fatty acids to protect and preserve the gut. If parenteral nutrition is necessary, special solutions may be necessary for the liver, kidneys, or lungs. If not, protein with 45% branched-chain amino acid, medium- and short-chain triglycerides, glutamine supplementation, and carbohydrates seem best. Other substances are being evaluated that may be helpful in nutrition and organ support, including arginine, xylitol, growth hormone, and anabolic steroids. Multiple organ failure should be prevented, if at all possible, by stopping or controlling the injury, removing as much necrotic tissue as possible, improving blood flow and oxygen consumption, supporting metabolism, and preventing infection or treating it early and adequately. Nutritional support plays a key role in preventing metabolic failure. PMID- 1904644 TI - Nutritional support in liver failure. AB - The most important manifestations of advanced liver disease are malnutrition, encephalopathy, and hepatorenal syndrome. Appropriate and optimal nutritional and metabolic support with specially formulated solutions enriched in branched-chain amino acids, together with other advanced treatments such as plasmapheresis, hemofiltration, and continuous arteriovenous hemodialysis, can correct the most important metabolic and clinical aberrations and temporarily improve the quality of life. However, the ultimately poor prognosis of patients with severe liver failure has not been altered significantly to date by the provision of nonspecific or specifically tailored nutrient regimens. The prognosis appears to depend on the arrest, correction, or reversal of the primary pathophysiologic process. PMID- 1904645 TI - Nutritional management of acute and chronic pancreatitis. AB - Acute pancreatitis often results in a catabolic state characterized by profound hemodynamic, metabolic, cardiovascular, pulmonary, hematologic, and renal aberrations. Parenteral nutrition and metabolic support are essential if morbidity and mortality are to be minimized. In chronic pancreatitis, nutritional management ranges from fundamental dietary manipulation with or without administration of appropriate digestive enzymes to enteral supplementation with modular chemically defined diets to total parenteral nutrition, depending on the stage, severity, and manifestations of the disease. In prescribing nutrient substrates in both acute and chronic pancreatitis, consideration must be given to their effects on pancreatic enzyme secretion if optimal results are to be achieved. PMID- 1904646 TI - Nutritional support in renal failure. AB - Adequate protein intake is necessary in renal failure to reduce morbidity. The desire to avoid dialysis should not be a justification to starve patients, particularly because fed patients have better survival rates in acute renal failure. The treatment techniques for renal failure may be used secondarily as a delivery route for nutrients. PMID- 1904647 TI - Nutritional management of inflammatory bowel disease. AB - The etiology and specific treatment of Crohn's disease and ulcerative colitis are unknown, and the treatment strategy for patients with inflammatory bowel disease is essentially symptomatic and supportive. The malnutrition that frequently accompanies inflammatory bowel disease is a manifestation of intestinal failure and should be vigorously corrected with total parenteral nutrition, elemental diets, or both. Evidence exists for the value of total parenteral nutrition and elemental diets as primary therapy for inflammatory bowel disease in selected patients. Judicious nutritional therapy remains a cornerstone in the adjunctive management of these patients. PMID- 1904648 TI - Management of the short-bowel syndrome. AB - The patient with short-bowel syndrome after massive small-intestinal resection represents one of the greatest clinical challenges a general surgeon must face. Maintaining optimal nutritional and metabolic support until maximum bowel adaptation can occur is the top priority of therapy. Currently, no operative procedure for adjunctive management of the short-bowel syndrome is sufficiently safe and effective to recommend its routine use. Long-term parenteral nutrition remains the cornerstone of successful management. PMID- 1904649 TI - Nutritional support of patients with AIDS. AB - Investigators are now predicting that nearly 100% of the estimated 12 million HIV positive persons in the world will develop AIDS. Most persons with AIDS will experience progressive weight loss and malnutrition prior to death. Because nutritional therapy clearly has a beneficial effect on the clinical course and immunologic status of the critically ill general population, one must not disregard its potential for benefits in the treatment of persons with AIDS. As a result of the escalating cost of medical therapy and the inevitable AIDS epidemic, the nutritional management of persons with AIDS must be simple to administer and cost effective. The author has developed nutritional screening criteria to identify those patients who would most benefit from nutritional therapy. Because these patients differ in their nutritional requirements, diet tolerance, and degree of gut dysfunction, there is no single nutritional therapy that can be used routinely to treat all malnourished persons with AIDS. PMID- 1904650 TI - Arrest and reversal of atherosclerosis with parenteral nutrition. AB - In a large subset of patients with atherosclerotic cardiovascular disease, all medical and surgical treatment alternatives have been exhausted or have proved to be ineffective. Intravenous infusion of specially formulated amino acid solutions, developed in the animal laboratory, has been efficacious in arresting and reversing atherosclerosis in humans for the first time. It is anticipated that the principles derived from these precise parenteral studies will eventually permit development of oral and enteral dietary formulations effective for the systemic control and management of atherosclerosis. PMID- 1904651 TI - [Diagnostic potential of a new functional test used in intestinal diseases- determination of hydrogen in exhaled air]. PMID- 1904652 TI - Adverse effects of treatment with porcine factor VIII. AB - In the last 10 years 63 courses (283 infusions) of porcine FVIII were given to 25 hemophiliacs with high titer alloantibodies and to 5 patients with autoantibodies to factor VIII. Although the product was in general clinically efficacious, adverse effects of treatment were more frequent and severe than previously reported. After 63 courses there was a median percentage fall in baseline platelet count of 54% (range 8-86%); for 10 courses (16%), thrombocytopenia was severe or moderately severe (less than 100 x 10(9)/l), with nadirs of platelet count ranging from 10 to 99 x 10(9)/l (median 67). Allergic reactions were seen in 15 of 30 patients (50%), in 20 of 63 courses (32%), more frequently but not exclusively after the first infusion. Relatively mild symptoms (fever, flushing, urticaria, shivering) occurred in 15 courses; 5 courses, however, were accompanied by more severe anaphylactoid reactions, 2 of which required resuscitation therapy. Allergic reactions were observed both in patients pretreated with steroids or anti-histamines (in 7 of 18 courses, 39%) and in nonpretreated patients (in 13 of 45 courses, 29%). In conclusion, adverse reactions are frequent after porcine FVIII (in 30 of 63 courses, 47%), and can occur also with infusions subsequent to the first. Hence, the recently proposed use of porcine FVIII as home treatment should be implemented with caution. PMID- 1904653 TI - Correlation between baseline plasminogen activator inhibitor levels and clinical outcome during therapy with tissue plasminogen activator for acute myocardial infarction. AB - Baseline plasminogen activator inhibitor (PAI) levels were examined for their influence on the responses to thrombolysis with recombinant tissue plasminogen activator (rt-PA) administered for acute myocardial infarction during the Thrombolysis and Myocardial Infarction (TAMI)-I study. Baseline PAI activity was 19 +/- 21 IU/ml (normal less than 5 IU/ml) and baseline PAI-1 antigen 54 +/- 53 ng/ml (normal 27 +/- 16 ng/ml), confirming previous findings of elevated PAI levels during acute myocardial infarction. Among clinical outcomes, lower PAI-1 antigen levels correlated weakly with greater patency at the 90 min angiogram. Thus, high baseline plasma PAI-1 levels may be detrimental to reperfusion with t PA. There was no correlation with other major in-hospital clinical outcomes including reocclusion at the 7-10 day angiogram, survival to discharge, or bleeding. During the follow up period of 2.0 +/- 0.4 years, no relationship between baseline PAI levels and post-discharge reinfarction was observed. PMID- 1904654 TI - Kinetic characterization of tissue-type plasminogen activator (t-PA) and t-PA deletion mutants. AB - The binding of t-PA to fibrin is mediated both by its "finger" (F) and its "kringle 2" (K2) domain. In addition, these domains are involved in the stimulation of t-PA activity by fibrin. We analyzed the kinetic characteristics of Glu-plasminogen activation by t-PA and a set of t-PA deletion mutants in the absence and the presence of desA-fibrin. In the absence of desA-fibrin, the activity of t-PA (variants) is determined by the presence of the protease domain, irrespective of the composition of the amino-terminal heavy chain. In the presence of the cofactor desA-fibrin, the activity of t-PA (variants) is dependent on the domain composition of the heavy chain. The activity of t-PA is stimulated 2,400 fold by desA-fibrin, whereas the activity of the mutant lacking the K1 domain (del. K1) increases 936 fold in the presence of this cofactor. Mutants lacking either the K2 domain (del. K2) or the F domain (del. F) exhibit an enhanced activity upon desA-fibrin addition of 200 and 210 fold, respectively. DesA-fibrin has no stimulatory effect on the activity of the mutant containing only the serine-protease domain (del.FE K1 K2) nor on the activity of the variant containing only the K1 domain and the serine-protease domain (del. FE K2). Furthermore, we determined the relative fibrin affinity of each t-PA variant, which is similarly dictated by the composition of the heavy chain. PMID- 1904656 TI - Abnormal platelet functions in a patient with abetalipoproteinemia. AB - Studies with isolated lipoproteins and washed platelets suggest that lipoproteins may affect platelet functions. We investigated platelet-rich plasma (PRP) from a patient with abetalipoproteinemia (ABL), whose plasma lacks apo-B containing lipoproteins (VLDL, LDL and chylomicrons). ABL-PRP aggregated poorly with different agonists and failed to respond to arachidonate. Thromboxane B2 (TxB2) formation was severely impaired. After gel-filtration most of the aggregation defects persisted in agreement with reduced metabolism of endogenous arachidonate. However, arachidonate-induced aggregation and TxB2 production partially normalized. Normal platelets suspended in ABL-plasma showed similar defects in aggregation and TxB2 production but arachidonate-induced aggregation was much lower than expected on the basis of TxB2. We conclude that the abnormal platelet functions in ABL-PRP are caused by (i) an intrinsic platelet abnormality due to reduced arachidonate mobilization and (ii) a property in ABL plasma that inhibits aggregation partially by trapping the arachidonate and partially by an unidentified mechanism. The latter properties may be the result of the abnormal lipid composition of ABL-plasma. PMID- 1904655 TI - Fibrinolysis and coagulation in patients with infectious disease and sepsis. AB - Sepsis is often associated with hemostatic dysfunction. This study aimed to relate changes in fibrinolysis and coagulation parameters to sepsis and sepsis outcome. Urokinase-type plasminogen activator (u-PA) antigen, tissue-type plasminogen activator (t-PA) antigen and activity, plasminogen activator inhibitor (PAI) type 1 antigen, PAI activity, antithrombin (AT) III activity, and protein C activity were measured in 24 patients suffering from sepsis or septic shock and the results were compared with those observed in 30 non-sepsis patients with severe infectious disease. The u-PA level was markedly increased in plasma of sepsis patients as compared to non-sepsis patients (11.5 +/- 9.4 versus 1.6 +/ 1.5 ng/ml, p less than 0.0001). PAI-1 antigen and t-PA activity showed a significant increase in sepsis patients (320 +/- 390 ng/ml versus 120 +/- 200 ng/ml, and 3.0 +/- 3.6 IU/ml versus 1.0 +/- 0.7 IU/ml, respectively, p less than 0.01). AT III was decreased in sepsis patients (58 +/- 28% in sepsis versus 79 +/ 26% in severe infectious disease, p less than 0.01) as was protein C (30 +/- 18% versus 58 +/- 27%, p less than 0.001). No significant difference was found for t PA antigen nor for PAI activity. Nonsurvivors of sepsis were distinguished mainly by a high u-PA antigen level and increased t-PA activity. It is concluded that plasma u-PA antigen showed the strongest significant difference, among the parameters evaluated, between sepsis and severe infection. u-PA antigen may be of prognostic value in patients admitted to the medical intensive care unit for severe infectious disease. PMID- 1904657 TI - Guidelines for testing and revised criteria for lupus anticoagulants. SSC Subcommittee for the Standardization of Lupus Anticoagulants. PMID- 1904658 TI - [Scrapie, still always a puzzling infection]. AB - Scrapie belongs to the spongiform encephalopathies in man and animals. The nature of the infectious agent, an "unconventional virus", has not been elucidated so far. The agent starts to replicate in lymphoid tissue, reaches high titers in the brain and induces the formation of amyloid in this organ. After trials to purify the agent, the infectivity proved to be associated with a protein, which has therefore been called "prion", and with rod-like structures from brain tissue (scrapie-associated fibrils, SAF). This protein is considered to be a reaction product of the infection rather than the infectious agent itself. PMID- 1904659 TI - A neurotoxic factor associated with the bloom-forming cyanobacterium Trichodesmium. PMID- 1904660 TI - Electromyographic assessment of the neuromuscular blockade produced in vivo by anatoxin-a in the rat. AB - The indirectly evoked compound action potentials (ECAP) of the plantar muscles of the rat were used to investigate the pharmacodynamics in vivo of the neuromuscular blockade produced by anatoxin-a. Onset time to maximum depression and the magnitude of maximum depression in amplitude of the ECAP were dose dependent. The mean maximum percent depression (+/- S.D.) of the ECAP induced by single, supramaximal stimulations of the posterior tibial nerve after i.v. doses of (+)anatoxin-a hydrochloride at 0, 50, 100, 200 and 800 micrograms/kg were 3 (4), 53 (15), 82 (7), 95 (2), and 100 (1), respectively. The ED50 (95% confidence limits) for depression of the ECAP was 47 mg/kg (39-57 micrograms/kg). Rats administered 200 micrograms/kg or less of (+)anatoxin-a hydrochloride had 75% return of the pretoxin amplitude of the ECAP within 93 min. Animals dosed at 800 micrograms/kg did not have return of neuromuscular function and died despite mechanical ventilation, suggesting a lethal mechanism(s) of action in addition to respiratory paralysis. Percent decrements (+/- S.D.) in the amplitude of the fourth ECAP following repetitive stimulation at 10 Hz were 6 (5), 13 (22), 46 (18) and 59 (8) from (+)anatoxin-a hydrochloride given i.v. at 0, 50, 100 and 200 micrograms/kg, respectively. The decrement observed following repetitive stimulation was attributed to a presynaptic site of action. No change in maximal motor nerve conduction velocity or latency of the ECAP was observed after i.v. administration of (+)anatoxin-a hydrochloride at 100 micrograms/kg. LD50 values (95% confidence limits) for anatoxin-a administered i.v. to mice were 386 micrograms/kg (365-408 micrograms/kg, for (+)anatoxin-a hydrochloride and 913 micrograms/kg (846-985 micrograms/kg) for racemic anatoxin-a hydrochloride. No deaths were observed in mice after i.p. administration of (-)anatoxin-a hydrochloride at doses up to 73 mg/kg. PMID- 1904661 TI - Intrafamilial spread of hepatitis C virus. PMID- 1904662 TI - OKT3 therapy for hepatic allograft rejection. Differential response in adults and children. AB - The clinical courses following OKT3 therapy for hepatic allograft rejection (HAR) in adults and children have not been individually defined. We have reviewed our experience with OKT3 therapy for HAR in adults and children to compare: (1) the initial response to OKT3 therapy, (2) the clinical course following OKT3 therapy, and (3) the antimurine antibody response and immunologic monitoring results. Children required OKT3 therapy more frequently than adults: fourteen courses of OKT3 therapy were required in 130 orthotopic liver transplants (OLT) in 108 adult patients, whereas nineteen courses of OKT3 therapy were required in 94 OLT in 78 children (P less than 0.02). Repeat OKT3 therapy was not required in adults- however, four of nineteen courses of OKT3 therapy in children were repeat OKT3 therapy for rejection. No differences existed between adult and pediatric treatment groups with respect to number of prior OLT procedures, previous graft loss to rejection, percentage of ABO-incompatible grafts, frequency of positive donor-recipient lymphocyte crossmatches, or time to first rejection. The initial response to OKT3 therapy (rapid reversal, delayed reversal, and failure) was remarkably similar in adults and children. However, nine of 13 (70%) children with clear evidence of response to OKT3 treatment experienced breakthrough rejection or early recurrent rejection, whereas none of 12 adults suffered breakthrough rejection or early recurrent rejection (P less than 0.01). Early recurrent rejection did not correlate with delayed reversal of rejection, early return of CD3+ cells by peripheral blood monitoring, or development of anti-OKT3 antibodies. All 4 courses of OKT3 retreatment in children were successful in reversing rejection, and breakthrough rejection and early recurrent rejection did not occur. Overall graft and patient survival in pediatric patients requiring OKT3 therapy (67% and 73%) was not different from that in adults (71% and 79%). Results obtained in one patient provide the first evidence that successful OKT3 retreatment of HAR can be achieved in the presence of preexisting idiotypic anti OKT3 antibody. In conclusion, OKT3 therapy for HAR was required more frequently in children than in adults. The clinical outcome following OKT3 therapy for HAR also differs markedly, with early recurrent rejection and breakthrough rejection occurring more frequently in children. PMID- 1904664 TI - Cyclosporine's dual mechanism of action in inhibiting generation of the cytoplasmic activation signal and the nuclear response thereto. AB - The mechanism of cyclosporine's action was dissected using protocols admixing cytoplasmic extracts to trigger isolated nuclei prepared after phytohemagglutinin, OKT3, or mixed lymphocyte culture stimulation of normal volunteer and renal transplant recipient lymphocytes. CsA at 100-1000 ng/ml doses prevented cytoplasmic extracts of cells activated in vitro by OKT3 or MLC from triggering incorporation of radiolabeled nucleotides by resting isolated nuclei. In addition, nuclei isolated from cells previously treated with 200-1000 ng/ml of CsA were refractory to the potent cytoplasmic signal extracted from OKT3- or MLC stimulated cells. CsA less effectively inhibited phytohemagglutinin-stimulated responses. CsA, but not its inactive analog cyclosporin H, inhibited 3H-thymidine incorporation into in situ nuclei. The inhibited cytoplasmic signal generation and nuclear responsiveness observed with normal lymphocytes exposed to CsA in vitro also was demonstrated with cells from renal transplant recipients who had been treated with CsA for less than 6 months. The impaired response of isolated patient lymphocyte nuclei to in vitro triggering with activated cytoplasmic extracts correlated with intranuclear CsA concentrations, but not with serum levels assessed with monoclonal antibodies selective for CsA or nonselective for CsA plus metabolites. Furthermore, patients displaying drug-induced nephrotoxicity had elevated intranuclear CsA, but not CsA plus metabolite, concentrations compared with stable transplant recipients. Thus, CsA addition in vitro or administration in vivo causes stereospecific inhibition, particularly for CD3 stimuli, of the cytoplasmic activation signal, and, to a lesser extent, of the subsequent nuclear response. PMID- 1904663 TI - Radiation-induced augmentation of host resistance to histocompatible tumor in mice. Detection of a graft antitumor effect of syngeneic bone marrow transplantation. AB - Lethally irradiated and syngeneic bone marrow-reconstituted (C57BL/6JxDBA/2J) F1 female mice demonstrated prolonged survival following challenge with the DBA/2 mastocytoma P815-X2 compared with non-irradiated littermate controls. This radiation-induced augmentation of host resistance to P815-X2 was not abolished by the adoptive transfer of normal syngeneic spleen cells. In addition, this phenomenon was not detectable in adult thymectomized recipients, suggesting the requirement for an intact host thymus. This effect was also absent in syngeneic F1 male recipients. We suggest that lethal irradiation and marrow reconstitution may result in activation of a nonspecific immune effector mechanism against tumor cells--and, as such, may serve as a model to explore the graft-antitumor effect of bone marrow transplantation. PMID- 1904665 TI - Cancer-associated hemolytic-uremic syndrome with spontaneous resolution. A case report. AB - A case of cancer-related hemolytic-uremic syndrome is reported. The patient presented a spontaneous recovery, which is unusual in this clinical picture. Mitomycin C is regarded as responsible for this toxic event in most cases. The case history reported here is discussed in relation to dose and scheduling of mitomycin C, and a safe maximum dosage is suggested. PMID- 1904666 TI - Resistance of the ME7 scrapie agent to peracetic acid. AB - Mouse brain infected with the ME7 strain of scrapie agent was exposed for 24 h to a range of concentrations of PAA, either as fragments of intact brain or as supernates of homogenised brain. Two % PAA inactivated the infectivity in intact tissue but not in a supernate. None of the concentrations tested (up to 19%) was effective with supernates, and this was considered to result from the protection afforded by aggregation of infectivity-containing particles. PMID- 1904667 TI - Differentiation by western blotting of immune responses of cattle vaccinated with Brucella abortus strain 19 or infected experimentally or naturally with virulent Brucella abortus. AB - Brucella abortus strain 19 salt-extractable proteins fractionated by differential ammonium sulfate precipitation were used in a western blotting method to detect bovine immunoglobulin G antibodies to B. abortus. Sera from infected cattle and from cattle vaccinated with strain 19 and subsequently exposed to virulent B. abortus bound to a common group of antigens ranging in molecular weights from 31,000 to 45,000 daltons. Immunoglobulin G antibodies in sera from the latter group in addition also bound to antigens with molecular weights of 66,000 to 71,000 daltons. Some sera from cattle vaccinated when sexually mature reacted similar to those from infected cattle, while immunoglobulin G antibodies in sera from Brucella-free cattle and vaccinated calves did not bind to either group of antigens. In general, fractionation of the proteins by ammonium sulfate precipitation offered no advantage for detecting differences between groups of sera. Ammonium sulfate fraction 0 to 35% reacted with a larger number of sera from a naturally infected group than fraction 0 to 70%. Both fractions reacted equally well with sera from the other groups of cattle, while fractions 35 to 70% and 70 to 100% reacted poorly in this technique. The attractive feature of the blot is that sera from calfhood-vaccinated cattle did not react. PMID- 1904669 TI - [The concentration of dissolved carbon dioxide maintaining the carbonate equilibrium in mineral waters]. PMID- 1904668 TI - An immunoturbidimetric assay for canine C-reactive protein. AB - Antiserum was raised in sheep against canine C-reactive protein (CRP) and antibody, which was not specific for CRP, was removed by absorption with normal canine serum protein linked to agarose beads. The antiserum was used to develop an immunoturbidimetric assay for canine CRP on a MIRA (Roche Diagnostics) automated clinical biochemical analyser and assessed for routine analysis of CRP in canine serum samples. The assay gave standard curves with each standard having a coefficient of variance (CV) between 4.8 and 11%, interassay CVs below 11% and intra-assay CVs of less than 5%. Parallel dilution curves were obtained with purified CRP diluted in buffer and with endogenous CRP in serum diluted with buffer or with a serum with a negligible CRP content. The immunoturbidimetric assay results correlated with the results obtained using an ELISA method, r = 0.88. The immunoturbidimetric assay of canine CRP proved to be suitable for the routine analysis of canine CRP. PMID- 1904670 TI - [Methods of isolation and quantitative analysis of fibronectin in biological fluids]. AB - The theoretical and methodological aspects of fibronectin isolation and quantitative determination in biological fluids are analysed on the basis of the communications available in the literature and the authors' own data. The procedure of applying the analyzed methods, potential complexity and errors in interpreting the data obtained by various methods are briefly outlined. Possible fields of their application, such as basic and clinical investigations, biotechnological production, etc. are also discussed. PMID- 1904671 TI - Age-related changes of J-chain-positive cells in chickens. AB - Localizations of J-chain-positive cells (JPC) were examined in chicken lymphatic tissues before and after hatching. The cells containing J chain were first detected in medullary areas of the bursa of FABRICIUS during the embryonic stage. These positive cells were partly detected in the developing small lymphatic follicles: perhaps on newly differentiating precursor B-cells. In addition to these lymphatic follicles, connective tissue of bursal fold were also detected as J-chain positive. Although similar localizations of JPC were again observed in hatched chickens, positive areas of follicular medulla were strongly stained for fluorescence with corresponding antisera than that of embryonic ones. These data may reflect differences in the physiology of lymphocytes in respect to functional development. JPC localizations were next compared between the B-cell subpopulations, mu-(microPC) and alpha-chain-positive cells (alpha PC). The J chains detectable in the IgM molecules were also found in follicular medulla. However, these follicles were almost found to be negative for J-chains detectable in the alpha PC before hatching. Any strong stainings for J-chain in the alpha PC were, moreover, not be observed in bursa after hatching. The microPC localizations in hatched chickens were roughly equal with the pattern of JPC localization. These analyses revealed the presence of the cells having the chains of both mu and J. The results together with other recent studies further shown that bursal J-chain can be partly detected in newly differentiated lymphatic follicles lacking IgM-producing and suggest the possible presence of B-cell differentiation sequence of Ig-J+----IgM+J+----IgA+J+. PMID- 1904672 TI - Carbonic anhydrase II in rat acid secreting cells: comparison of osteoclasts with gastric parietal cells and kidney intercalated cells. AB - Location of carbonic anhydrase II, an important enzyme involved in acid production, was studied using an immunogold method on ultracryosections. Its distribution in osteoclasts was compared with that in gastric parietal cells and kidney intercalated cells of the inner stripe of outer medulla. It is shown that the distribution of carbonic anhydrase II is much similar in all of these acid producing cells: most of the enzyme is cytoplasmic and nucleoplasmic and only a small fraction of the enzyme is associated with the apical plasma membrane. It seems likely that carbonic anhydrase II has a similar role in all of these acid producing cells. PMID- 1904673 TI - Intrathecal synthesis of free immunoglobulin light chains and IgM in initial multiple sclerosis. AB - We studied the intrathecal synthesis of free kappa, free lambda immunoglobulin light chains and of IgM in 33 consecutive patients with possible or probable MS at the time of their first diagnosis. Nineteen patients presented free kappa or lambda light chain bands in CSF after agarose isoelectric focusing, protein transfer to nitrocellulose and immunostaining with specific antisera. Nineteen patients had increased CSF levels of free kappa light chains as measured with a competitive ELISA. Fourteen had an increased IgM index, as evaluated with a sandwich ELISA. Twenty-six patients displayed CSF oligoclonal IgG bands in CSF and 25 had cerebral magnetic resonance imaging lesions suggestive of MS. The local production of free immunoglobulin light chains and IgM is often detected in the CSF of patients with early MS. PMID- 1904674 TI - Secretin dissipates red acridine orange fluorescence from pancreatic duct epithelium. AB - This study was undertaken to elucidate whether duct cells in the pancreas contain acidic cytoplasmic compartments regulated by secretin. Microdissected pancreatic ducts from pigs were examined by acridine orange (AO) and 2',7'-biscarboxyethyl 5(6)-carboxyfluorescein/tetraacetoxymethy l ester (BCECF/AM) epifluorescence microscopy. Estimated cytoplasmic pH using BCECF fluorescence was 7.43 +/- 0.04 and was not changed by altering CO2 tension in the incubation medium. The epithelium of acridine orange incubated peripheral interlobular pancreatic ducts exhibited green and red fluorescence; the colour depending on the experimental conditions. Red epithelial fluorescence was seen in resting pancreatic ducts and was greatly accentuated by raising CO2 in the incubation medium from 5.5 to 10 kPa. The red fluorescence was abolished by secretin, or following incubation with chloroquine or NH4Cl or the protonophores carbonyl cyanide p trifluoromethoxyphenylhydrazone (FCCP) or carbonyl cyanide m chlorophenylhydrazone (CCCP), leaving uniform green fluorescence. These findings suggest that pancreatic duct cells contain CO2-dependent acidic compartments which vanish during secretin stimulation and which may be cytoplasmic tubulovesicles. PMID- 1904675 TI - Membrane-bound carbonic anhydrase CA IV in the human kidney. AB - The distribution of membrane-bound carbonic anhydrase, CA IV, was studied in human kidneys by an indirect immunoperoxidase method using a rabbit polyclonal antibody directed against human kidney CA IV. Clear staining of CA IV was found in the apical cell borders of some cells in the cortical and medullary segments of the collecting ducts, presumably the A type of intercalated cells. Weak staining for CA IV was located in the interior of a number of collecting duct cells and in the basolateral regions of the proximal convoluted tubules. However, no staining was found in the brush border of the same tubules. This is a surprising finding, since evidence for carbonic anhydrase activity has been found biochemically and histochemically both in isolated brush-border and baso-lateral membranes. Further work is needed to clarify this matter. The endothelium of the peritubular capillaries also stained for CA IV. PMID- 1904676 TI - Metabolic correlates to pacemaker activity in the smooth muscle of guinea-pig mesotubarium. AB - Oxygen consumption (FO2) and lactate production (Flac) were measured during spontaneous activity in the guinea-pig mesotubarium. During spontaneous contractions FO2 increased to maximally 0.270 +/- 0.025 mumol min-1g-1 (n = 23), followed by a rapid fall immediately upon relaxation. In the relaxed period (5-15 min) between spontaneous contractions FO2 continued to slowly decrease by about 25% towards a final value of 0.150 +/- 0.01 mumol min-1g-1. Flac showed no consistent variation during the relaxed period. Ouabain (10(-6)M) produced a contracture, which was abolished by the Ca2(+)-antagonist felodipine (10(-6)M). In the presence of felodipine, addition of ouabain caused depolarization and a decrease of oxygen consumption by 21% and of lactate production by 31%. Exchange of glucose in the physiological Krebs solution for beta-hydroxybutyrate did not influence spontaneous activity, while subsequent addition of cyanide (2 mM) abolished contractions and caused a hyperpolarization of 15 mV. Blockade of ATP dependent K+ channels by addition of glibenclamide (10(-7)M) to the relaxed muscle in this situation caused spontaneous contractile activity to reappear. In glucose-containing Krebs solution glibenclamide had no effect on the spontaneous contractile and electrical activity and contractions persisted after addition of cyanide. The relaxing and hyperpolarizing effect of pinacidil could be counteracted by addition of glibenclamide. The results suggest that a decrease in electrogenic Na+/K(+)-pump activity in the course of the relaxed period between contractions could contribute to the pacemaker behaviour. ATP-dependent K+ channels, while having little influence on the spontaneous contractile activity under normal metabolic conditions, could be activated during blockade of aerobic and anaerobic metabolism, leading to inhibition of pacemaker activity. PMID- 1904677 TI - Immunocytochemical demonstration of c-fos protein in sertoli cells and germ cells in rat testis. PMID- 1904679 TI - Effect of radiation therapy on thoracic and lumbar bone marrow: evaluation with MR imaging. AB - Bone marrow suppression is often the limiting factor in the use of radiation therapy. In order to determine if MR imaging can be used to quantify bone marrow changes, we performed a serial prospective study of patients with lung cancer (six cases) and lymphoma (six cases). Quantitative and qualitative assessments of T1-weighted sagittal images, 750/33 (TR/TE), obtained at 0.6 T before, during, and after radiotherapy showed increased signal intensity in the radiated portions of the spine. These changes appeared as early as 2 weeks after the beginning of radiation, continued to increase until a maximum value was attained, and then persisted during the follow-up period of 2 years. A significantly higher (p less than .04) ratio of pretreatment to maximum posttreatment signal intensity was seen in patients with lymphoma than in those with lung cancer, and pretreatment values in patients with lymphoma were significantly lower (p less than .01). The lower pretreatment values found in the patients with lymphoma may have been due to the smaller amount of yellow marrow in these patients, who were significantly younger (33 vs 62 years). The higher ratio of pre- and posttreatment signal intensity may have been related to the larger amount of hematopoietic marrow available to undergo fatty replacement. The persistence of elevated signal intensity for as long as 2 years after radiation suggests an endpoint in the process of marrow conversion, but not reversal in the form of regeneration of hematopoietic bone marrow. Quantitative MR evaluation of bone marrow may be of considerable value as a noninvasive means of monitoring the effects of radiotherapy. PMID- 1904678 TI - Ureteral pseudodiverticula: frequent association with uroepithelial malignancy. AB - Ureteral pseudodiverticula are tiny outpouchings usually seen as incidental findings on retrograde urography during routine work-up for common urinary tract disorders. We report 37 patients with ureteral pseudodiverticula, of whom 17 (46%) had associated uroepithelial malignancy. Ureteral pseudodiverticula were diagnosed in all patients on excretory or retrograde urography as an incidental finding during evaluation for a variety of urologic symptoms and signs. All patients were assessed with urinalysis, urine culture, cystoscopy, and when indicated, ureteroscopy. Diagnosis of transitional cell carcinoma was made by surgery or endoscopic biopsy in 16 patients and squamous cell carcinoma in one. In nine patients with radiographs showing ureteral pseudodiverticula and a urinary tract filling defect (usually in the bladder), 78% of the cases were proved malignant. In six patients with ureteral pseudodiverticula and a stricture in the ureter or renal collecting system, 67% of the cases were proved malignant. Of the patients with tumor, 53% had a single ureteral pseudodiverticulum. In two cases, the pseudodiverticula antedated the diagnosis of malignancy by 2 and 4 years, respectively. Our experience suggests that the association between ureteral pseudodiverticula and uroepithelial malignancy may be more common than previously assumed, approaching 50%. Even a single ureteral pseudodiverticulum should be regarded as a serious marker for potential malignancy, antedating cancer by 2-10 years, and such patients should be closely followed up. The coexistence of ureteral pseudodiverticula and a stricture or filling defect in the urinary tract is highly suggestive that a tumor is present. PMID- 1904680 TI - Immunotactoid glomerulopathy and cutaneous vasculitis. AB - A 22-year-old woman presented glomerulonephritis with Schonlein-Henoch-like syndrome and monoclonal abnormality. One month later, she developed a rapidly progressive glomerulonephritis with hypertension and persistent purpura. In the two renal biopsies performed during the first and the second attack, mesangial expansion and thickening of the glomerular capillary walls (associated with 50% of crescents in the second biopsy) were observed on light microscopy. By immunofluorescence faint deposits of immunoglobulins (light and heavy chains) and complement components were found present in the mesangium. Electron microscopy showed tubular microfibrils measuring 19-24 nm in the mesangium, subendothelial and subepithelial areas. A skin biopsy performed during the first attack demonstrated leukocytoclastic skin vasculitis. By immunofluorescence, no deposits were observed. Congo red staining for amyloid and cryoglobulinemia were negative. This case is similar to an entity recently described and named immunotactoid glomerulopathy. PMID- 1904681 TI - A randomized trial evaluating leuprolide acetate before hysterectomy as treatment for leiomyomas. AB - Fifty premenopausal patients requiring hysterectomy as treatment for symptomatic uterine leiomyomas, which were the size of 14 to 18 weeks' gestation, were randomized into two groups to determine whether preoperative gonadotropin releasing hormone agonist would increase the feasibility of vaginal rather than abdominal hysterectomy. The control group (group A; n = 25) did not receive preoperative gonadotropin-releasing hormone agonist, but patients in Group B (n = 25) received 2 months of gonadotropin-releasing hormone agonist before undergoing hysterectomy. Patients in the two groups were similar with respect to age, gravidity, parity, pretreatment uterine size, and hemoglobin and hematocrit levels. Patients in group B had an increase in hemoglobin levels (10.75 to 12.12 gm/dl, p less than 0.05) and a decrease in uterine volume (1086.7 to 723.4 ml, p less than 0.05) after 8 weeks of agonist therapy and were more likely to undergo vaginal hysterectomy (76.0% vs 16%). Patients in group B also had shorter hospitalizations (5.2 vs 3.8 days, p less than 0.05). We conclude that the administration of gonadotropin-releasing hormone agonist for 2 months followed by vaginal hysterectomy is preferable to abdominal hysterectomy in selected patients with uterine leiomyomas. PMID- 1904682 TI - Mechanisms of asphyxial brain damage, and possible pharmacologic interventions, in the fetus. AB - An examination of the cellular and molecular mechanisms of neuronal cell damage may lead to the design of pharmacologic interventions during presumed or actual fetal asphyxia. Hypoxia-ischemia in its severest form results in insufficient adenosine 5'-triphosphate production. The most important effect of this is failure of adenosine 5'-triphosphate-dependent membrane functions, which maintain ionic homeostasis, that is, ionic pumping. There is K+ efflux and Na+ influx across the cell membrane, depolarization of the cell membrane, opening of the voltage-dependent calcium channels, and entrance of Ca++ into the cell. Cytosolic Ca++ is also increased by Ca++ efflux from the mitochondria and the sarcoplasmic reticulum. Ca++ is a toxin in high cytosolic concentrations; it activates phospholipases A and C, which cause membrane breakdown and release of free fatty acids, including arachidonic acid. The membrane is damaged, lysis occurs, and the neuron dies. High cytosolic Ca++ also causes release of excitatory amino acids (especially glutamate), which overwhelm the suppressant neurotransmitters, causing seizures, increased metabolism, and aggravation of the insufficient adenosine 5'-triphosphate availability. Thromboxane A2 is generated from arachidonic acid, increasing smooth muscle tone and thereby worsening the ischemia. Cyclooxygenase activity also results in formation of oxygen-free radicals that contribute to cell membrane damage, lysis, and death. Possibilities for pharmacologic interventions include (1) calcium channel blockers and antagonists, (2) excitatory neurotransmitter blockers, (3) oxygen-free radical scavengers (e.g., superoxide dismutase), (4) cyclooxygenase or prostaglandin synthesis inhibitors, and (5) seizure suppressants (e.g., phenobarbital). Some of these treatments have been shown experimentally to limit neuronal death in the adult and fetus, and after more investigative work they may be applicable to clinical practice. PMID- 1904684 TI - Glucose challenge testing in pregnancy. AB - This study examines results of routine glucose challenge screening in 608 third trimester patients in a private practice setting. Four patient categories were defined on the basis of the results: normal, abnormal screen with normal glucose tolerance test, borderline glucose tolerance test, and gestational diabetes. When only standard prenatal management practices were used, the fetal outcomes in the four groups were not measurably different. The costs of these procedures resulted in an expenditure of $722.31 per diagnosis of gestational diabetes. This seems excessive in view of the negligible impact of these studies on fetal outcome. Our impression was that routine third-trimester dietary counseling, postprandial glucose monitoring without challenge testing, and evaluation of cases of suspected fetal macrosomia would result in comparable outcome at significantly reduced cost. PMID- 1904683 TI - Hormonal inhibition of the endometrium for resectoscopic endometrial ablation. AB - Attempts at inhibiting the thickness and vascularity of the endometrium in preparation for endometrial ablation by using different types of hormones have been reported. To evaluate the effects of two different progestins, danazol, and leuprolide acetate on the endometrium, compared with the features of early proliferative endometrium, histologic studies were done for at least five patients treated with each hormone who then underwent resectoscopic endometrial ablation for treatment of abnormal uterine bleeding. Significant and at times dramatic differences among the treatment groups were found, with progestin prepared endometrium being the least successful and leuprolide-prepared endometrium the most successful. In addition, the prolonged suppression provided for a period of time after the procedure by depot leuprolide is likely to help inhibit endometrial regeneration and provide even better long-term success of the procedure. PMID- 1904685 TI - A comparison of the cost-effectiveness of two types of occupational therapy services. AB - The demand for efficient and effective health care prompted this study comparing the treatment outcomes and personnel costs of two types of occupational therapy service provision for the patient with a total hip replacement. System 1 used traditional individual treatment as the primary service provision method, with group treatment used as an adjunct. System 2 used group treatment as the primary intervention method, with individual treatment as the adjunct. Program evaluation research found the study subjects to be demographically homogeneous with no difference in treatment outcomes relative to four specific functional performance goals. Direct labor costs, however, were reduced by more than one third for the System 2 patients. The results of this study suggest that for specific rehabilitation patient populations, group treatment could be a cost-effective method of occupational therapy service provision. PMID- 1904686 TI - The transition from nonoral to oral feeding in children. AB - In this single-subject study, an evaluation was completed to determine the effect of occupational therapy intervention on the oral intake of 3 children who had their nutritional needs met by nonoral methods prior to the administration of an oral feeding program. Treatment consisted of a gradual increase of food presentation with the application of behavioral management methods and the presentation of developmentally appropriate play activities. Oral intake was measured during baseline and intervention phases to establish the effect of intervention. An analysis indicated an increase in oral intake in the intervention phase in 2 of the 3 children. The results, that occupational therapy intervention can increase the oral intake of children in transition from nonoral to oral feeding, might be strengthened through the replication of this study on larger populations. PMID- 1904687 TI - End-tidal CO2 monitoring in mitral stenosis patients undergoing closed mitral commissurotomy. AB - Arterial to end-tidal carbon dioxide difference (P(a-E')CO2) was recorded in 20 mitral stenosis patients (group A) for closed mitral commissurotomy and 20 healthy individuals (group B) for elective limb surgery. Mitral stenosis patients showed a greater difference than group B patients. Repeated measurements of P(a E')CO2 in mitral stenosis patients at various stages of closed mitral commissurotomy not only showed a mean increase from before thoracotomy but there was also no correlation between P(a-E')CO2 before thoracotomy with that after thoracotomy, after commissurotomy or after chest closure. This indicated that end tidal CO2 monitoring was unsuitable to measure adequacy of ventilation during closed mitral commissurotomy. PMID- 1904688 TI - An isolated grand mal seizure 5 days after propofol anaesthesia. PMID- 1904689 TI - [The mechanism of the reduction of protein catabolism following trauma and during sepsis using xylitol]. AB - Total parenteral nutrition (TPN) after trauma and sepsis has two major goals. One is the reduction of enhanced protein catabolism; the second is the avoidance of enhancement of whole-body glucose turnover. Glucose and xylitol differ in their quantitative utilization rate after trauma and sepsis. Maximal glucose utilization is reduced during such states, while the utilization of xylitol is more than doubled. In order to investigate whether these differences are associated with beneficial effects with regard to whole-body glucose turnover rate of gluconeogenesis and protein sparing, we conducted two studies using animal models and two clinical studies. METHODS. For the determination of glucose and protein turnover, radioactive and stable isotope techniques were applied. In an animal model a primed constant infusion of 3-H-6-glucose, 14-C-1-alanine and 13-C-3-alanine and 14-C-U-acetate was used to determine total glucose appearance, gluconeogenesis from 3-C-precursors and alanine flux. In the human studies hepatic glucose production was determined by using a primed constant infusion of 6.6-D-2-glucose and urea synthesis rate was determined by a primed constant infusion of 2-N-15-urea. RESULTS. In the first rat model we were able to show that hypocaloric xylitol compared to glucose significantly reduced whole-body glucose turnover from 1741 +/- 232 mumol/h during glucose infusion to 449 +/- 49 mumol/h during xylitol infusion and gluconeogenesis from C-3 carbons form 382 +/- 24 mumol/h during glucose infusion to 155 +/- 39 mumol/h during xylitol infusion after a burn trauma. In a second septic rat model the exchange of glucose calories by xylitol in a proportion of 1:1 was associated with a significantly ameliorated N-balance from +144 +/- 90 mgN/kg body weight per day during glucose infusion to +699 +/- 80 mgN/kg body weight per day during glucose-xylitol infusion and a reduced 3-methyl-histidine excretion from 7.14 +/- 0.61 mumol/kg body wt. per day during glucose infusion to 4.10 +/- 0.56 mumol/kg per day during glucose-xylitol infusion, respectively. In two studies with surgical intensive care patients we were able to confirm the nitrogen-sparing properties of xylitol infusion, together with amino acids during hypocaloric feeding or during TPN with a glucose/xylitol mixture in a proportion of 1:1. From a basal urea production rate of 9.2 +/- 1.6 mumol/kg min. xylitol led to a significant reduction with 6.4 +/- 1.5 mumol/kg per min. Hepatic glucose production was significantly reduced during xylitol infusion from basal 4.8 +/- 0.6 mg/kg per min to 3.1 +/- 0.7 mg/kg per min, respectively. Equicaloric glucose in a dosage of 3 g/kg per day had no effect. During TPN glucose/xylitol, in a proportion of 1:1 at a total dosage of 0.24 g/kg per h, significantly reduced whole-body glucose turnover, endogenous glucose production and lactate concentrations compared to an isocaloric glucose infusion. DISCUSSION. In animal as well as in human studies hypocaloric xylitol as well as a glucose-xylitol mixture were more efficient in preserving body protein than glucose alone. Whole-body glucose turnover was significantly reduced during hypocaloric xylitol or glucose-xylitol infusion compared to isocaloric glucose infusion. During the acute phase after trauma we therefore recommend a carbohydrate supplementation of 3 g/kg body wt. per day using xylitol. During long-term TPN, a glucose-xylitol mixture in a proportion of 1:1 in a dosage of 3 g/kg body wt. per day each is recommended as energy source, together with amino acids and, if necessary, lipids. PMID- 1904690 TI - Sulfate composition of glycosaminoglycans determined by infrared spectroscopy. AB - Anhydrous sodium sulfate (Na2SO4) was analyzed at varying concentrations by infrared (ir) spectroscopy. A standard curve was obtained from a linear plot of sulfate (SO2-(4] concentration vs the weight of the ir band area of S = O stretching. Standard chondroitin 4-sulfate, chondroitin 6-sulfate, heparan sulfate, heparin, keratan sulfates, and various dermatan sulfates isolated from human and rat skins were also studied by ir spectroscopy. The spectrum of every glycosaminoglycan (GAG) displayed an ir band around 1230 cm-1 which originated from S = O stretching of sulfate esters. Therefore, the weight of the latter band was employed to quantify sulfate, by using the standard curve indicated above. Sulfate was also estimated quantitatively by the gelatin/BaCl2 method of K.S. Dodgson and R.G. Price (Biochem. J. 1962, 84, 106-110). The sulfate composition determined by ir spectroscopy ranged from 8.5 to 22.1% (w/w), and agreed closely with the values obtained chemically. In the ir spectroscopy method, sulfate was determined using the polymer forms of the GAGs. After analysis, these heteropolysaccharides were recovered unaffected in a yield greater than 95%. The data show that the infrared spectroscopy technique, in addition to being sensitive and reliable, is much more economical than the chemical procedures currently employed to quantify GAG sulfate. PMID- 1904691 TI - Adaptation of an enzymatic fluorescence assay for L-glutamic acid decarboxylase. AB - The activity of L-glutamic acid decarboxylase (GAD) is commonly estimated by several radiometric methods, whereas a fluorimetric assay based on an enzymatic formation of NADPH as described by Y. Okada and C. Shimada [(1975) Brain Res. 98, 202-206] has been given little attention in biochemical and pharmacological investigations. A simple modification of this assay is presented to permit rapid and sensitive GAD measurements in unpurified tissue homogenates. This method, employing a linear NADPH standard curve, is demonstrated to be a valid assay system for a pharmacological approach using 3-mercaptopropionic acid. PMID- 1904692 TI - Carbonic anhydrase assay: strong inhibition of the leaf enzyme by CO2 in certain buffers. AB - Apparent carbonic anhydrase activity in leaf extracts, measured as the rate of H+ production associated with the CO2 hydration reaction, varied by as much as 25 fold when the assay buffer was varied. Highest activities were usually recorded in barbitone buffer, with lower activities in imidazole, Tricine, Hepes, Tris, and phosphate buffers. The greatest differences were observed with the enzyme isolated from leaves of the monocotyledonous plants Zea mays (maize) and Triticum aestivum (wheat). Smaller differences were observed with carbonic anhydrase from dicotyledonous species and there was no effect on the erythrocyte enzyme. Leaf carbonic anhydrase activity measured by the mass spectrometric procedure was unaffected by varying the assay buffer. The low activity in certain buffers observed with the former assay system was found to be due to inhibition of the enzyme-catalyzed reaction by higher concentrations of CO2. Carbonic anhydrase from some sources was also strongly inhibited by certain inorganic and organic anions. PMID- 1904693 TI - [Lysine metabolism in man]. AB - Lysine is an important amino acid: it is incorporated to collagene, one of the most important component of conjonctive tissue and, though, necessary for growth. It is also important for carnitine synthesis. Its intestinal absorption requires two transport systems that lysine shares with ornithine, arginine and cystine for the former and with ornithine and arginine for the latter. The same transport systems are present in the hepatocytes, were lysine is extensively catabolized, and in renal tubular cells. The main catabolic pathway for lysine, via saccharopine, is a mitochondrial pathway leading to acetyl-CoA. The peroxisomal pathway, via pipecolic acid is of less physiological importance and is mainly active in brain. The existence of the two minor pathways, the acetyllysine pathway and the lysine-urea cycle, remains to be demonstrated. PMID- 1904694 TI - [Inborn errors of lysine metabolism]. AB - A wide variety of inborn errors of lysine catabolism have been described. They include: abnormalities of the mitochrondrial catabolism via the "saccharopine pathway", abnormalities of the peroxisomal catabolism via the pipecolic pathway, and "lysine intolerance with periodic ammonia intoxication" linked to urea cycle pathway. These inborn errors are associated with a wide variety of clinical symptoms and biochemical profiles as persistent hyperlysinemia, saccharopinuria, "amino and ketoadipic aciduria, and glutaric aciduria. PMID- 1904695 TI - [Lysine and collagen]. AB - The amount of lysine in collagen is only 3 or 4% of total aminoacids, but it has an important function in the constitution of the cross-links between the molecules to built the fibrils and the fibers of collagen. For this function, some lysine molecules must be hydroxylated and other oxidized to aldehyde compounds. Some deficits in these metabolic pathways are responsible for heritable diseases of the connectivite tissue as types IV and IX of the Ehlers Danlos syndrome, lathyrism, the Menkes kinky hair syndrome, Cutis-Laxa or the type II of osteogenesis imperfecta. The contribution to fibrosis is also discussed. PMID- 1904696 TI - [Lysine and human nutrition]. AB - Lysine is one of the 8 essential amino acids, i.e. it is not synthetized by the body. As such, lysine has been the object of controversy for numerous years with regard to recommended daily intake. Initially defined in terms of nitrogen balances, these values have been increased following studies based on stable isotopes. In parenteral nutrition, the supply of lysine is generally between 0.39 and 0.55 g/g of nitrogen, with the exception of products for babies (Primene, Vaminolac) in which values are higher. In the light of the metabolic pattern in pathologic situations and the speed of metabolization of perfused lysine, it would appear that lysine supplies are excessive. In certain states of malnutrition such as in patients with renal failure, large supplies of lysine are not only unnecessary but contra-indicated since this amino acid shows a certain degree of nephrotoxicity. Finally, in spontaneous nutrition, excessive lysine intake would appear to be atherogenic. PMID- 1904697 TI - [Hyperlysinemia and hyperammonemia]. AB - A quite important increase of plasma lysine was often reported in different cases of hyperammonemia. This retrospective study of patients with different types of hyperammonemia shows that hyperlysinemia is not automatically associated to hyperammonemia (lysinemia is expressed as the percent of total aminoacidemia). Hyperlysinemia was observed with neonatal propionic and methylmalonic acidurias. Reye's syndrome and to a less extent with ornithine transcarbamylase deficiency. PMID- 1904698 TI - [A decision tree for abnormalities of plasma and urine lysine level]. AB - Variations of plasma lysine were divided in four situations: decreased, slightly decreased to normal, normal to slightly increased and always very increased. From each of these situations, and with the concentrations of urinary lysine; a flow chart is proposed for aminoacidopathies and organic acidurias in which lysine metabolism is primarily or secondarily disturbed. PMID- 1904699 TI - [Lysine in human biologic fluids and tissues: reference values, physiologic variations and interferences]. AB - The authors present here the published values of lysine in some biological fluids, plasma, urine, CSF, amniotic fluid, aqueous humor, sweat. The plasma levels are lower in newborn infants than in adult subjects. The urinary excretion of lysine is high in the first pregnancy, the lysine concentration of amniotic fluid decreases progressively. A sex difference has been described in CSF: values higher in men. Changes occur in lysine concentrations when samples are not prepared for analysis immediately after collection and certain drugs interfere with analysis. PMID- 1904700 TI - Hepatotoxicity of rifampin and isoniazid. Is it all drug-induced hepatitis? AB - Serologic markers for hepatitis viruses were studied in 40 children who developed acute hepatitis during antituberculosis therapy with rifampin and isoniazid, with the aim of assessing the contributory role of these viruses toward producing hepatic injury. Hepatitis A and B were confirmed in 7.5 and 35% patients, respectively, by IgM antibodies. Epidemiologic evidence suggested the possibility of non-A, non-B hepatitis in at least a few of the remaining 23 children. Hepatitis B was seen more often in children with severe tubercular disease (72%) and was largely (92.8%) parenterally transmitted. The study highlights that the endemicity of viral hepatitis in developing countries, among other factors, could also be responsible for the reported higher incidence of hepatotoxicity from developing countries and also for the increased risk of hepatotoxicity seen in severe tubercular disease. PMID- 1904701 TI - Isocapnic hyperventilation for measuring airway hyperresponsiveness in asthma and in chronic obstructive pulmonary disease. PMID- 1904702 TI - Anaerobic degradation of cresols by denitrifying bacteria. AB - The initial reactions in anaerobic metabolism of methylphenols (cresols) and dimethylphenols were studied with denitrifying bacteria. A newly isolated strain, possibly a Paracoccus sp., was able to grow on o- or p-cresol as sole organic substrate with a generation time of 11 h; o- or p-cresol was completely oxidized to CO2 with nitrate being reduced to N2. A denitrifying Pseudomonas-like strain oxidized m- or -p-cresol as the sole organic growth substrate completely to CO2 with a generation time of 14 h. Demonstration of intermediates and/or in vitro measurement of enzyme activities suggest the following enzymatic steps: (1) p Cresol was metabolized by both strains via benzoyl-CoA as central intermediate as follows: p-cresol----4-OH-benzaldehyde----4-OH-benzoate----4-OH-benzoyl-CoA----be nzoyl-CoA. Oxidation of the methyl group to 4-OH-benzaldehyde was catalyzed by p cresol methylhydroxylase. After oxidation of the aldehyde to 4-OH-benzoate, 4-OH benzoyl-CoA is formed by 4-OH-benzoyl-CoA synthetase; subsequent reductive dehydroxylation of 4-OH-benzoyl-CoA to benzoyl-CoA is catalyzed by 4-OH-benzoyl CoA reductase (dehydroxylating). (2) o-Cresol was metabolized in the Paracoccus like strain via 3-CH3-benzoyl-CoA as central intermediate as follows: o-cresol--- 4-OH-3-CH3-benzoate----4-OH-3-CH3-benzoyl-CoA----3-CH3-benzo yl-CoA. The following enzymes were demonstrated: (a) An enzyme catalyzing an isototope exchange reaction between 14CO2 and the carboxyl of 4-OH-3-CH3-benzoate; this activity is thought to be a partial reaction catalyzed by an o-cresol carboxylase. (b) 4-OH-3-CH3-benzoyl-CoA synthetase (AMP-forming) activating the carboxylation product 4-OH-3-CH3-benzoate to its coenzyme A thioester. (c) 4-OH-3 CH3-benzoyl-CoA reductase (dehydroxylating) catalyzing the reductive dehydroxylation of the 4-hydroxyl group with reduced benzyl viologen as electron donor to yield 3-CH3-benzoyl-CoA. This thioester may also be formed by action of a coenzyme A ligase when 3-CH3-benzoate is metabolized. 2,4-Dimethylphenol was metabolized via 4-OH-3-CH3-benzoate and further to 3-CH3-benzoyl-CoA. (3) The initial reactions of anaerobic metabolism of m-cresol in the Pseudomonas-like strain were not resolved. No indication for the oxidation of the methyl group nor for the carboxylation of m-cresol was found. In contrast, 2,4- and 3,4 dimethylphenol were oxidized to 4-OH-3-CH3- and 4-OH-2-CH3-benzoate, respectively, probably initiated by p-cresol methylhydroxylase; however, these compounds were not metabolized further. PMID- 1904703 TI - Molecular cloning and expression of Spirulina platensis acetohydroxy acid synthase genes in Escherichia coli. AB - The coding sequence for Spirulina platensis acetohydroxy acid synthase (AHAS, EC 4.1.3.18) is shown to be contained within a 4.2 Kb ClaI fragment (ilvX) that has been cloned from a recombinant lambda library. This fragment was able to complement a suitable mutant of Escherichia coli when inserted into the ClaI site of plasmid pAT153 in either orientation, demonstrating that transcription of ilvX originated within the cloned fragment. The probe used for hybridization experiments was the corresponding gene from Anabaena sp. PCC7120. The same probe allowed us to identify a second putative gene encoding AHAS in the S. platensis genomic library. PMID- 1904704 TI - [Lead poisoning in children. Apropos of 129 cases]. AB - One hundred and twenty nine children with chronic lead poisoning were followed from August 1985 to July 1989. Old lead paint was recognized as the contaminant source at home. Pica of paint flakes was the main mode of intoxication. Children were classified according to the Center for Disease Control 1985 as follows: class IV (39 cases), class III (45 cases), class II (30 cases), class I (15 cases). Nineteen of those in class IV had blood lead levels above 700 micrograms/l and received BAL + EDTA followed by EDTA alone for a mean of 4.6 +/- 3.5 courses. With this treatment, blood lead level decreases were 50 +/- 17%. Nine of these class IV children had an evaluation at last 3 months after the last chelation course: 5 became class I or II, and 2 class III with a negative provocative test. The remaining 20 children in class IV were given a mean of 2.7 +/- 1.4 courses of EDTA. Blood lead levels decreased by 52 +/- 15%; 11 children were evaluable at least 3 months after the last chelation course: 4 became class I, and 7 class II. Thus overall 80% of class IV moved under treatment to class I or II. Among those 45 children in class II, 30 underwent a provocative test and 24 one to three courses of EDTA: 8 were further studied: 3 became class I and 5 class II. Combination of screening, medical treatment and sociocultural approach led to avoid acute effects of severe chronic childhood lead poisoning. The efficacy of such an approach in preventing chronic effects has still to be evaluated. PMID- 1904705 TI - [Syndrome associating: osteopetrosis, tubular acidosis, mental retardation and cerebral calcifications due to carbonic anhydrase II deficiency. Apropos of 3 cases in the siblings]. AB - Three new cases of a syndrome including osteopetrosis, tubular acidosis, mental retardation and cerebral calcifications are reported in the same sibship. This rare syndrome has an autosomal recessive inheritance and is due to carbonic anhydrase II deficiency. Fractures and mild sensorial manifestations were noticed in 2 cases. Mental deficiency and otitis were present in the 3 cases. Blood count and phosphocalcic metabolites were normal. A proximal tubular acidosis was present in each case. The radiological features were specific: cerebral calcifications were present in all cases since the age of 2 1/2 years; osteocondensation and bone modeling were predominant in long bones metaphyses. Alcalinization improved the height growth. PMID- 1904706 TI - Lysine requirement of growing steers. AB - Eight Limousin-cross steers (355 kg) were used in a replicated 4 x 4 Latin-square designed to estimate lysine requirements. Steers were fed a semipurified diet containing little ruminal escape protein. Treatments were abomasal infusions of 0, 8, 16, or 24 g/day L-lysine. All steers were additionally infused with 400 g/day dextrose and 285.9 g/day of an amino acid mix that contained (g/day) L methionine (12.0), L-histidine (8.1), L-arginine (10.5), L-threonine (12.0), L valine (18.0), L-isoleucine (13.8), L-leucine (27.3), L-phenylalanine (28.2), L glutamic acid (76.5), glycine (76.5) and L-tryptophan (3.0); it had been demonstrated previously that when lysine was included in this infusion mixture, nutritional requirements of steers for maximal N retention were met or exceeded. Nitrogen retention averaged 38 g/day and was not affected by treatment, implying that the lysine requirement of steers was less than the 37.8 g/day lysine estimated to be absorbed from the small intestine when the basal diet was fed. PMID- 1904707 TI - Dysphagia: a staged transition to oral nutrition. PMID- 1904708 TI - Cytokine interactions in experimental cutaneous leishmaniasis. AB - Destruction of intracellularly living Leishmania major amastigotes is achieved by activated macrophages. In this report, we have investigated the contribution of IL-4, TNF-alpha and IFN-gamma to the induction of antileishmanial macrophage activation. It was found that as single lymphokine only IFN-gamma led to amastigote elimination by peritoneal exudate macrophages. Neither IL-4 nor TNF alpha or the combination of both cytokines led to antimicrobial activation. When the macrophages were incubated with concentrations of IFN-gamma that by themselves were insufficient for maximum cell activation, it was found that both IL-4 and TNF-alpha very effectively synergized with IFN-gamma for induction of antiparasitic activity. The activation which was achieved when IFN-gamma was combined with IL-4 could be blocked not only with antibodies to either of the lymphokines, but also with an antiserum specific for TNF-alpha, suggesting the involvement of endogenously generated TNF-alpha in this synergism. Any of the synergistic activities observed presumably lead to the activation of the L arginine dependent pathway used by the cell for the production of nitrogen oxides as effector molecules for parasite killing since NG-monomethyl-L-arginine (L NMMA), a specific inhibitor of this pathway, completely blocked the killing of intracellular parasites. We conclude that macrophage activation for antiparasitic activity is directed by a complex network of cytokine-interactions, in which IL-4 and TNF-alpha very effectively synergize positively with low levels of IFN-gamma. PMID- 1904709 TI - The immune response to Mycobacterium tuberculosis. AB - Mycobacteria are worldwide spread and satisfactory vaccines against pathogenic species have not been developed, yet. Mycobacteria, inside phagocytic cells, are able to escape humoral attack and maintain viability for long periods of time. T cells are engaged in the activation and regulation of macrophages and subsequently, in the control of mycobacterial growth. It appears that different T cell sets including CD4 alpha/beta T cells, CD8 alpha/beta T cells and gamma/delta T cells are involved in antimycobacterial immunity. Both, phagocyte and microorganism synthesize heat shock proteins in order to facilitate their survival. HSP possesses potent immunogenicity, a high degree of homology among different species and hence may play an important role in resistance against and pathogenesis of mycobacterial infections. PMID- 1904710 TI - Human gamma/delta T cells responding to mycobacteria. AB - Responses of human T cells against mycobacteria and mycobacterial components were analysed. T cells expressing either the alpha/beta or the gamma/delta T cell receptor were selected from human peripheral blood lymphocytes and proliferative responses to intact mycobacteria and to molecular mass-fractionated mycobacterial lysates were determined. alpha/beta T cells responded primarily to fractions greater than 30 kDa. Protease digestion abolished the stimulating activities for alpha/beta T cells, confirming that alpha/beta T cells respond to protein components. In contrast components recognized by gamma/delta T cells proved resistant to protease digestion. In limiting dilution studies, frequencies of proliferating gamma/delta T cells remained virtually unaltered by protease treatment of stimulating lysates, while those of alpha/beta T cells became almost undetectable. Furthermore, only few gamma/delta T cells responded to the 65 kDa heat shock protein. Our data indicate that, unlike alpha/beta T cells, gamma/delta T cells respond to mycobacterial components which are resistant to vigorous protease digestion. PMID- 1904711 TI - T-cell responses during infections with Leishmania major. PMID- 1904712 TI - CD4+T cell-dependent effector mechanisms important in the immune response to the erythrocytic stages of Plasmodium chabaudi chabaudi (AS). AB - The ability to produce IFN-gamma during an erythrocytic infection with P. chabaudi chabaudi is not an indicator of resistance or susceptibility of mice to this infection. However, IFN-gamma may play a transient role in immune control of the parasite. We have shown that after its removal in vivo by antibody treatment the acute phase of infection is clearly exacerbated. After the acute phase of infection the T cell response changes from one characterized by IFN-gamma production to one of a T helper response for antibody production. The IFN-gamma response to parasite challenge can be recovered if the challenge infection is given many weeks after the mice have cleared their primary parasitaemias. These data suggest that the CD4+ T cell response is a heterogenous one and regulated by its cytokine production. The protective mechanisms therefore probably reflect the nature of the ongoing immune response. PMID- 1904713 TI - T cell subsets in granulomatous inflammation and immunity to L. Monocytogenes and B. abortus. AB - The phenomenological reevaluation of cellular immunity to L. monocytogenes and B. abortus revealed that the inflammatory reactions accompanying both infections, i.e. DTH, splenomegaly and granulomatous inflammation, are mediated exclusively by CD4+ T cells. On the other hand, as shown in the acute Listeria-model as well as in the more chronic murine Brucellosis, specific CD8+ T cells are able to mediate protective mechanisms in the absence of any granulomatous monocyte accumulation. In an attempt to determine the cytokines responsible for monocyte accumulation and antibacterial protection we could show that IFN-gamma and TNF, both discussed as proinflammatory as well as macrophage activating cytokines, both can be produced in a T-cell-dependent as well as in a T-cell-independent manner. The ability of listeria-specific CD8+T cells to secrete TNF and IFN-gamma in response to listerial antigen argues against a role of these cytokines as mediators of granuloma formation. PMID- 1904714 TI - Genetic basis for remating in Drosophila melanogaster. IV. A chromosome substitution analysis. AB - Drosophila melanogaster lines previously selected for fast and slow return of female receptivity were subjected to a chromosome substitution analysis. Chromosomal effects on direct response to selection were distinctively different between selection lines derived from two different base populations. All three chromosomes tested affect the trait in the JEFFERS selection lines. In contrast, only chromosome II was found to have a main effect in the COMP selection lines. Significant interactions between chromosome II and the other chromosomes were also found in both of the selection lines. All of the components of virgin fly mating behavior measured were affected by chromosome II. PMID- 1904716 TI - Genetic basis for remating in Drosophila melanogaster. VI. Recombination analysis. AB - Drosophila melanogaster lines previously selected for fast and slow return of female receptivity were used for two different recombination analyses. Major loci affecting the difference between the fast and the slow remating speed map to the right arm of chromosome II to the right of welt (wt). PMID- 1904715 TI - Genetic basis for remating in Drosophila melanogaster. V. Biometrical and planned comparisons analyses. AB - Drosophila melanogaster lines previously selected for fast and slow return of female receptivity were crossed to produce 16 lines (2 parental, 2 F1, 4 F2, and 8 backcross lines). Several genetic hypotheses could be tested both through particular planned comparisons among these 16 crosses and with a biometrical analysis. Both analyses identified the difference between the fast and the slow remating speed in these lines as having an autosomal basis. This is in agreement with observations from previous chromosome-substitution analyses. However, the planned comparisons yielded no significant deviations from expectations based on no dominance, no X-chromosomal factors, and no permanent cytoplasmic factors, whereas the biometrical analysis yields the best fit when some of these factors are included. PMID- 1904717 TI - Site-directed mutagenesis of dicarboxylic acids near the active site of Bacillus cereus 5/B/6 beta-lactamase II. AB - An amino acid residue functioning as a general base has been proposed to assist in the hydrolysis of beta-lactam antibiotics by the zinc-containing Bacillus cereus beta-lactamase II [Bicknell & Waley (1985) Biochemistry 24, 6876-6887]. Oligonucleotide-directed mutagenesis of cloned Bacillus cereus 5/B/6 beta lactamase II was used in an 'in vivo' study to investigate the role of carboxy group-containing amino acids near the active site of the enzyme. Substitution of asparagine for the wild-type aspartic acid residue at position 81 resulted in fully functional enzyme. An aspartic acid residue at position 90 is essential for beta-lactamase II to confer any detectable ampicillin and cephalosporin C resistance to Escherichia coli. Conversion of Asp90 into Asn90 or Glu90 lead to the synthesis of inactive enzyme, suggesting that the spatial position of the beta-carboxy group of Asp90 is critical for enzyme function. PMID- 1904718 TI - Leucine and glutamine metabolism in septic rats. AB - The rate of leucine C-2 incorporation into glutamine was compared in control and septic rats. Female Sprague-Dawley rats (n = 46, 210-260 g) were fed parenterally for 3 days and then randomized into two groups (control and septic). Sepsis was induced by the injection of 10(10) live Escherichia coli/kg on day 4 into the septic group. Rats in each group were given a continuous (8 h) infusion of one of three different isotopes. The isotopes were given 24 h after inoculation. Leucine oxidation and incorporation into protein were determined with [1-13C]leucine; glutamine flux and oxidation were determined with [5-13C]glutamine, and the fraction of leucine C-2 incorporated into glutamine was determined by giving [1,2 13C]leucine. Results were as follows: sepsis caused a significant increase in the rate of leucine C-2 incorporation into glutamine (66.0 +/- 3.7 as against 29.6 +/ 3.7 mumol/h per kg, P less than 0.01). This increase was due to both an increase in glutamine production (2331 +/- 76 as against 1959 +/- 94 mumol/h per kg, P less than 0.01) and an increase in the proportion of glutamine derived from leucine (2.83 +/- 0.27% as against 1.51 +/- 0.31%, P less than 0.01). The ratio of leucine C-2 incorporated into glutamine to leucine oxidized increased from 7.16 +/- 0.91% to 11.49 +/- 1.12% with sepsis (P less than 0.05). PMID- 1904719 TI - Structural properties of long- and short-chain alcohol dehydrogenases. Contribution of NAD+ to stability. AB - Structural studies were undertaken on long-chain and short-chain alcohol dehydrogenases (from horse liver and Drosophila respectively). Far-u.v. c.d. measurements were used to estimate the secondary structure contents of the enzymes. For the horse liver enzyme, the results agree well with the X-ray data; for the Drosophila enzyme (for which a crystal structure is not yet available), the results are in good agreement with those obtained by applying a range of structure-prediction procedures to the amino acid sequence of this enzyme. The conformational stabilities of the two enzymes were investigated by studying the unfolding brought about by guanidinium chloride (GdnHCl) by using activity and c.d. measurements. The unfolding of the Drosophila enzyme was analysed in terms of a two-state model; the presence of the substrate NAD+ leads to considerable protection against unfolding. By contrast, the unfolding of the horse liver enzyme shows a plateau effect at intermediate concentrations of GdnHCl, indicating that a two-state model is not appropriate in this case. NAD+ affords little, if any, protection against unfolding for the horse liver enzyme. PMID- 1904720 TI - Alterations in the accumulation of adenylylated nucleotides in heavy-metal-ion stressed and heat-stressed Synechococcus sp. strain PCC 6301, a cyanobacterium, in light and dark. AB - Heavy-metal-ion- (Cd2+, Cu2+, Pb2+, Hg2+ and Zn2+) or heat (50 degrees C)-stress treatments of the unicellular cyanobacterium Synechococcus sp., strain PCC 6301, under both light and dark conditions led to the accumulation of bis(5' nucleosidyl)oligophosphates: Ap4A, Ap4G, Ap3A, Ap3G and Ap3Gp2. Under light regimens, the accumulation of Ap4A and Ap4G is more characteristic of heavy-metal ion-stressed cells, whereas the accumulation of Ap3A, Ap3G and Ap3Gp2 is the dominant feature of heavy-metal-ion or heat-shock treatment during energy deprivation (i.e. in the dark). This accumulation of bisnucleoside oligophosphates supports a model whereby the adenylylated nucleotides are synthesized by the backward reaction of tRNA-aminoacyl synthetases. These nucleotides may also act to switch or modulate cyanobacterial responses under various environmental stress conditions. PMID- 1904722 TI - Specificity of guanylic RNases to polynucleotide substrates. AB - Kinetic parameters kcat and KM were measured for cleavage of poly I, poly A, poly U, poly C and poly I poly C by guanyl-specific RNases Sa, Pb1 and T1 and compared with that of guanyl-preferential RNase Bi. Catalytic efficiencies of the investigated enzymes to polynucleotide substrates vary considerably. The structural basis for specificity of these RNases is discussed. A hypothesis is suggested that Ser-56 plays an important role in recognition of poly A by RNase Bi. PMID- 1904723 TI - Muscarinic receptor antagonist effects in parotid acini and M1-CHO cells: evidence of G protein involvement. AB - We have examined the effects of the muscarinic antagonist atropine, on non receptor-mediated activation of intracellular calcium (Ca2+i) mobilization events. In dispersed rat parotid acini, atropine significantly lowered basal inositol trisphosphate levels and delayed AlF4(-)-stimulated Ca2+i elevation in a dose-dependent manner. In a cell line transfected with the m1 muscarinic receptor (M1-CHO), atropine significantly lowered (approximately 60%) AlF4- stimulated Ca2+i elevation. These aggregate findings suggest that atropine, acting via the muscarinic receptor, decreases the efficacy of G protein-mediated activation of phospholipase C. PMID- 1904721 TI - Restoration of arylsulphatase B activity in human mucopolysaccharidosis-type-VI fibroblasts by retroviral-vector-mediated gene transfer. AB - The Maroteaux-Lamy syndrome (mucopolysaccharidosis type VI; MPS VI) is a lysosomal storage disease caused by deficiency of the enzyme arylsulphatase B (ASB). A human ASB cDNA has been subcloned into the retroviral vector pXT1 containing the bacterial neomycin-resistance gene and an internal thymidine kinase promoter for transcription of the inserted gene. Replication defective retrovirus was generated by transfecting the construct into the amphotropic packaging cell line PA317. Human MPS VI fibroblasts infected with recombinant retrovirus integrated the provirus into their genome and expressed retrovirus encoded ASB mRNAs. In infected fibroblasts the level of ASB was up to 36-fold higher than in normal fibroblasts. Biosynthesis and processing of ASB in infected MPS VI fibroblasts was accomplished as in normal fibroblasts, and mature, enzymically active, ASB accumulated in dense lysosomes, indicating that the ASB deficiency in MPS VI fibroblasts was corrected by the retroviral gene transfer. PMID- 1904724 TI - Mastoparan increases membrane permeability in rat parotid cells independently of action on G-proteins. AB - Mastoparan, a peptide toxin from wasp venom, stimulated the accumulation of inositol phosphates in rat parotid acinar cells. Addition of this peptide to fura 2-loaded cells resulted in a rapid increase in the fura-2 fluorescence ratio (340 nm/380 nm), suggesting that mastoparan stimulates an increase in cytosolic Ca2+ concentration. However, this change in the ratio appears to be due, in part, to fura-2 leakage from the cells, because addition of Mn2+, which quenches extracellular fura-2 fluorescence, reduced the increased fluorescence ratio. In addition to the fura-2 leakage, mastoparan caused considerable leakage of lactate dehydrogenase, a cytosolic marker enzyme. Furthermore, mastoparan decreased the number of trypan blue-excluding cells, indicating a decrease in cell viability. These results suggest that mastoparan enhances the membrane permeability by a mechanism independent of the activation of G-proteins. PMID- 1904725 TI - Central basic fibroblast growth factor inhibits gastric ulcer formation in rats. AB - We have recently reported that basic fibroblast growth factor (bFGF) acts in the brain to inhibit the secretion of gastric acid and pepsin, two major aggressive factors in the pathogenesis of gastric ulcer formation. In the present study, we determined whether or not bFGF has an anti-ulcer action via the central nervous system, using male Wistar rats. The intracisternal injection of bFGF dose dependently (0.1-1.0 microgram(s)/rat) inhibited the severity of gastric ulcers induced by water-immersion restraint stress or central thyrotropin-releasing hormone. The same doses of peripherally injected bFGF failed to protect the gastric mucosa from these ulcerogenic procedures. These results suggest for the first time that bFGF has a mucosal protective effect through a mechanism involving the central nervous system. It is speculated that this anti-ulcer action of bFGF is, at least in part, dependent upon its gastric antisecretory effect. PMID- 1904726 TI - Influence of captopril on glucose and fatty acid oxidation in human thrombocytes and mononuclear leucocytes. AB - Captopril (CAS 62571-86-2) may be beneficial for the treatment of diabetes because of its activating effect on peripheral glucose consumption besides its well known blood pressure degradation. The glucose oxidation has been found to be activated by captopril in thrombocytes and mononuclear leucocytes, cell types which are usually considered to be independent from insulin. Because the oxidation of pyruvate labelled in position C-1 but not of 2-14C-pyruvate and of 1 14C-acetate was enhanced, captopril most probably stimulated the pyruvate decarboxylation reaction. The metabolism of glucose labelled in positions 1 and 6 was equally activated by captopril indicating another step which may be affected by captopril. PMID- 1904727 TI - Trauma systems and public policy. PMID- 1904728 TI - The 20-year experiment: accounting for, explaining, and evaluating health care cost containment in Canada and the United States. PMID- 1904729 TI - Long-term care financing: problems and progress. PMID- 1904730 TI - [Care plan or nursing care plan?]. PMID- 1904731 TI - [The spending of service pressure moneys. Bedpan or personnel?]. PMID- 1904732 TI - [Hospital Hilversum. Closely involved in new building]. PMID- 1904733 TI - [Nurse and law. The judge, the employment contract and the performance evaluation]. PMID- 1904734 TI - ['To become demented must be the worst there is'. Nursing care and treatment of patients with AIDS-related neurological disorders]. PMID- 1904735 TI - [Empathetic communication with elderly patients with dementia]. PMID- 1904736 TI - [A chronically ill child--a task for the entire family]. PMID- 1904737 TI - [Report: pain-infusion equipment]. PMID- 1904738 TI - [Mental health--nurses in action]. PMID- 1904739 TI - [Zuiderziekenhuis Rotterdam. Learning from each other]. PMID- 1904740 TI - [Money for employment policy. Work experience locations are effective]. PMID- 1904741 TI - [HBO-V-Organizational version in Nijmegen. Result of regional cooperation between nursing education and practice field (Higher Professional Nursing Education)]. PMID- 1904742 TI - [Social support from the perspective of psychiatric nursing]. PMID- 1904743 TI - [Nursing and its professional education--in relation to developments in health care]. PMID- 1904744 TI - [Report: Homemaker services--home care services]. PMID- 1904745 TI - Control of components of bacterial polysaccharide vaccines by physical methods. AB - Analysis of polysaccharide components of meningococcal- and pneumococcal vaccines was carried out by proton n.m.r. spectroscopy and gas chromatography. The meningococcal polysaccharides were of high purity but showed differences in degree and position of O-acetylation between manufacturers. The level of contamination of the pneumococcal polysaccharides by C-substance was quantified. These methods provide an alternative to immunological methods for determining serotype and purity. PMID- 1904746 TI - A reference preparation for human immunoglobulin against Crimean/Congo hemorrhagic fever. PMID- 1904747 TI - Effects of MPTP, MPP+, and paraquat on NADPH-dependent lipid peroxidation in mouse brain and lung microsomes. AB - Both MPTP and MPP+ inhibited the NADPH-dependent microsomal LPO in mouse brain and lung. On the other hand, PQ significantly stimulated the LPO in brain microsomes in a dose-dependent manner. The herbicide, however, stimulated lung microsomal LPO only in a narrow concentration range, despite much higher P450 reductase activity in lung microsomes than that in brain microsomes. These findings suggest that the effect of PQ on microsomal LPO is different from those of the analogous neurotoxins, MPTP and MPP+, and is not uniform in brain and lung. PMID- 1904748 TI - 'Glutaraldehyde'. PMID- 1904749 TI - Effect of racemic ibuprofen dose on the magnitude and duration of platelet cyclo oxygenase inhibition: relationship between inhibition of thromboxane production and the plasma unbound concentration of S(+)-ibuprofen. AB - 1. Four healthy male subjects received racemic ibuprofen (200, 400, 800 and 1200 mg), orally, on four occasions, 2 weeks apart, according to a four-way Latin square design, in order to investigate the influence of increasing dose of ibuprofen on the magnitude and duration of its antiplatelet effect as well as on the relationship between such effect and drug concentration. 2. The antiplatelet effect of ibuprofen was assessed by measuring the inhibition of platelet thromboxane B2 (TXB2) generation during the controlled clotting of whole blood. The plasma unbound concentration of S(+)-ibuprofen, the enantiomer shown in an in vitro study to be responsible for the inhibitory effect of platelet TXB2 generation, was measured using an enantioselective method. 3. The maximum percentage inhibition of TXB2 generation increased significantly with dose from a mean +/- s.d. of 93.4 +/- 1.2% after the 200 mg dose to 98.8 +/- 0.3% after the 1200 mg dose, and there was an increase with dose in the duration of inhibition of TXB2 generation. The effect of ibuprofen on platelet TXB2 generation was transient and mirrored the time-course of unbound S(+)-ibuprofen in plasma; on all but one of the 16 occasions, serum TXB2 concentrations returned to at least within 10% of the pretreatment concentrations within 24 h of ibuprofen administration. 4. For each subject, the relationship between the percentage inhibition of TXB2 generation and the unbound concentration of S(+)-ibuprofen in plasma was modelled according to a sigmoidal Emax equation. The mean plasma unbound concentration of S(+)-ibuprofen required to inhibit platelet TXB2 generation by 50% (EC50) was 9.8 +/- 1.0 micrograms l-1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1904750 TI - A dose-response study examining the effects of ritanserin on human slow wave sleep. AB - This study investigated the effects of placebo, 1 mg, 3 mg, 10 mg and 30 mg ritanserin and 10 mg diazepam on human sleep. Twelve normal volunteers participated in this randomized, double-blind, placebo-controlled cross-over sleep study. A clear dose-response relationship was found for ritanserin with higher doses evoking increased duration of slow wave sleep. PMID- 1904751 TI - Excretion of fluvoxamine in breast milk. PMID- 1904752 TI - Pharmacological activity of the dinitrate metabolites of nitroglycerin following their oral administration to healthy volunteers. PMID- 1904753 TI - Disposition of gamma-glutamyl levodopa (gludopa) after intravenous bolus injection in healthy volunteers. AB - 1. The pharmacokinetics of gludopa in healthy volunteers were studied at two doses, 250 micrograms kg-1 and 100 micrograms kg-1, after rapid intravenous bolus injection. 2. Gludopa had a clearance of 4.43 +/- 1.50 ml min-1 kg-1 and 4.92 ml min-1 kg-1 at the higher and lower doses, respectively. Corresponding half-lives were 29.2 +/- 3.7 min and 32.5 +/- 5.6 min, and volumes of distribution were 0.183 +/- 0.052 l kg-1 and 0.235 +/- 0.07/ l kg-1. 3. Urinary excretion of dopamine rose sharply after injection of gludopa at both doses, peaking at 30 min. At this time, amounts were over 215 and 60 times baseline values at the higher and lower dose of gludopa, respectively. Urinary dopamine rose in parallel with urinary levodopa excretion, supporting the view that levodopa is the precursor of urinary dopamine. 4. Less than 1% of the injected dose of gludopa was excreted unchanged in the urine. 5. These findings suggest that, in man, gludopa is an efficient pro-drug for dopamine. Gludopa may find therapeutic use in conditions where the beneficial renal effects of dopamine may be indicated. PMID- 1904754 TI - Biliary and other gastrointestinal interventions. AB - Over the past several years, renewed interest in biliary endoprostheses has developed among interventional radiologists. The experimental, technical, and clinical progress that produced this enthusiasm is reviewed, with emphasis on recently published reports. The application of percutaneous enterostomy for gastric decompression or feeding has become widely practiced, and recent reports of percutaneous and endoscopic gastrostomy are compared, with emphasis on controversial points. The technique of percutaneous enterostomy has been adapted for jejunal and colonic application, and these technical modifications, as well as miscellaneous biliary and gastrointestinal interventions, comprise the remainder of the review. PMID- 1904755 TI - Survival of Listeria monocytogenes in egg washwater. AB - The viability of Listeria monocytogenes strains Scott A, 78-34, and 81-861 in artificial egg washwater at different temperatures and pH values was determined. After a 4-h incubation, less than a 1-log decrease in viability of strains Scott A and 78-34 was found at 33 degrees C with alkaline detergent (pH 8.0-10.5); however, up to a 3-log decrease in viable numbers was found in neutral pH controls lacking detergent. At 42 degrees C, survival was generally poorer; complete loss of viability (greater than 4-log decrease in viable numbers) was found within 2 h at neutral pH. Strain 81-861 was more sensitive to the test conditions than the other two strains. Viability of all strains was markedly lower in synthetic washwater at the lower pH values (pH 7-9) containing whole egg than washwater in which whole egg was omitted. The presence of whole egg appeared to have no effect on survival at pH 10.5. A limited survey of two egg wash facilities in Southeastern Ontario revealed Listeria innocua in environmental samples from both plants, and in washwater from one plant. These results suggest that Listeria spp. can survive normal commercial washwater conditions, and can be found in commercial egg wash plants. PMID- 1904756 TI - Characterization of plasmids from Listeria sp. AB - Out of 139 isolates of Listeria sp. (mainly L. monocytogenes) 107 (78%) contained extrachromosomal DNA. Plasmids from 51 of these isolates were investigated further and covered a range of 8 different-sized molecules as shown by agarose gel electrophoresis. Only one of the 107 isolates contained more than one plasmid. With the exception of one plasmid from an isolate of L. seeligeri, restriction analysis and hybridization experiments showed a high degree of homology between the different plasmids. PMID- 1904757 TI - Heme-dependent catalase activity of lactobacilli. AB - The heme-dependent catalase in Lactobacillus pentosus, L. sake, L. delbrueckii and Enterococcus faecalis was studied. The catalase was formed by cells grown aerobically in the presence of hematin or for lactobacilli when grown without added hematin, after incubation of buffered cells in the presence of hematin. The kinetics of the production of catalase revealed maximum activity for L. pentosus and E. faecalis at late stationary and late logarithmic growth phase, respectively. The physiological role of catalase was studied with L. sake. The presence of hematin allows higher growth yields, since it protects the cells against hydrogen peroxide formed endogenously up to concentrations of 4.6 mmol/l. PMID- 1904758 TI - Capsular polysaccharide of a slime-forming Lactococcus lactis ssp. cremoris LAPT 3001 isolated from Swedish fermented milk 'langfil'. AB - Slime-forming Lactococcus lactis ssp. cremoris strain LAPT 3001 isolated from Swedish ropy sour milk 'langfil' was investigated for the chemical nature of its capsule. The capsular material purified by gel filtration chromatography and ion exchange chromatography consisted of rhamnose, glucose, galactose, glycerol and phosphorus. It is most likely a deacylated lipoteichoic acid. PMID- 1904759 TI - The incidence of Listeria monocytogenes in slaughtered animals, in meat, and in meat products in Yugoslavia. AB - 45% of all pigs examined harboured L. monocytogenes in the tonsils, and 3% were faecal excretors. L. monocytogenes was demonstrated in 29% of swabs from the retropharyngeal nodes of cattle and in 19% of faecal samples. The tonsillar and retropharyngeal samples did not correspond to the faecal samples. L. monocytogenes was not demonstrated in the deeper parts of the muscle tissue from 12 beef carcasses all harbouring Listeria in lymph nodes. L. monocytogenes was found in 69% of minced meat (mixed pork and beef) samples. 19% of raw dry sausages and 21% of vacuum-packaged hot smoked sausages were positive for L. monocytogenes. L. monocytogenes was not detected in the hot smoked sausages heated to an internal temperature of 70-75 degrees C, after the smoking process. PMID- 1904760 TI - Incidence of Listeria species in seafood and seafood salads. AB - A total of 128 samples of seafood on the Icelandic market were tested for the presence of Listeria monocytogenes and other Listeria species. The samples included raw, smoked and dried fish, frozen shellfish and shrimps as well as several fish salads. These products are generally consumed without heating. Listeria spp. were present in 56% of the samples of raw fish, 29% of the smoked fish, 9% of the shrimps and 32% of the salads. No Listeria spp. were present in the shellfish or dried fish. In 46% of the positive samples L. monocytogenes could be demonstrated, either alone or together with L. innocua. The other positive samples contained L. innocua and, in one sample, L. welshimeri. All products sampled had been processed and packed in Iceland, mostly for use on the domestic market. It is suggested that consuming certain fish products and fish salads may form an additional risk factor for listeriosis in humans. PMID- 1904761 TI - The occurrence of Listeria species in milk and dairy products: a national survey in England and Wales. AB - A total of 4172 samples of milk, cheese and other dairy products were examined over a 1-year period for the presence of Listeria species. Strains of Listeria were found most frequently in soft, ripened cows milk cheese; 63 out of 769 (8.2%) samples contained Listeria monocytogenes, 25 samples contained species other than L. monocytogenes, and 18 samples contained both L. monocytogenes and other Listeria spp. Eleven samples of pasteurized cows milk (1.1%) from four dairies contained L. monocytogenes, and other Listeria spp. were isolated from a further five samples. Goats and ewes milk and their products, yogurt, cream and ice cream also occasionally contained Listeria spp. Levels of Listeria were usually low, but 20 samples of cheese contained more than 1000 cfu/g. Most strains of L. monocytogenes belonged to serotype 1/2 (58%) or serotype 4b (33%). PMID- 1904762 TI - Effect of temperature history on the growth of Listeria monocytogenes Scott A at refrigeration temperatures. AB - The effect of pre-inoculation temperature on the subsequent growth of Listeria monocytogenes Scott A at 5 degrees C was examined in microbiological medium, UHT milk, canned dog food, and raw ground beef (untreated and irradiation sterilized). In microbiological medium, the duration of the lag phase was decreased when aerobic and anaerobic cultures were initially grown at less than or equal to 28 and less than or equal to 13 degrees C, respectively. Subsequent exponential growth rates and maximum population densities of the 5 degrees C cultures were not affected by temperature history. Differences in lag phase durations were also observed when L. monocytogenes initially cultured at 19 and 37 degrees C were grown at 5 degrees C in UHT milk and some of the canned dog food varieties. Growth of L. monocytogenes was not observed in either untreated or irradiation-sterilized raw ground beef. While temperature history can affect the growth kinetics of L. monocytogenes at 5 degrees C, it did not account for the lack of growth in raw meat, suggesting that there is an inhibitory condition or component in ground beef that is lost upon cooking. PMID- 1904763 TI - Survey of the incidence of Listeria monocytogenes and other Listeria spp. in experimentally irradiated and in matched unirradiated raw chickens. AB - Listeria spp. were sought in 32 chickens experimentally irradiated (2.5 kGy) and in 25 matched unirradiated chickens. Using the modified Food and Drug Administration method only three of the chickens were positive for L. monocytogenes. Using the more sensitive cold enrichment method 30 were found positive. The proportion of carcasses contaminated with L. monocytogenes was lower in the irradiated birds than in the unirradiated birds. The results also indicated that the numbers of L. monocytogenes in the irradiated birds were lower than in the unirradiated birds. The only other species of Listeria isolated was L. innocua, which was found on 44% of unirradiated chickens, but on none of the irradiated chickens. PMID- 1904764 TI - Incidence of Aeromonas and Listeria spp. in red meat and milk samples in Brisbane, Australia. AB - A total of 150 samples, 50 each of beef, lamb and pork from 10 local retail stores in Brisbane metropolitan area as well as 150 raw bovine bulk milk tank samples obtained from Queensland United Foods (QUF), were examined for the presence of Aeromonas and Listeria spp. over a period of 1 year. Different sets of enrichment and plating media were used to recover the organisms with subsequent identification using conventional biochemical and serotyping techniques. A total of 509 isolates consisting of Aeromonas spp. (350) and Listeria spp. (159) were obtained from 60%, 58%, 74%, 26.6%, 34%, 40%, 30%, 2.6% of samples of beef, Lamb, pork and milk respectively. Motile aeromonads (A. hydrophila, A. sobria, A. caviae) and Listeria innocua were isolated from all kinds of samples whereas L. monocytogenes was only isolated from flesh food. A. hydrophila contributed the largest percentage of the motile aeromonads (60%). The majority of L. monocytogenes cultures were serotype 4. PMID- 1904765 TI - Comparison of a cold enrichment and the FDA method for isolating Listeria monocytogenes and other Listeria spp. from ready-to-eat food on retail sale in the U.K. AB - A cold enrichment and the modified FDA selective enrichment method were compared for their ability to detect Listeria monocytogenes and other Listeria species from various ready-to-eat foods on sale in the UK. Of 57 food samples examined using cold enrichment, five yielded L. monocytogenes, and two L. innocua. The FDA enrichment method yielded three samples positive for L. monocytogenes only. Foods examined included soft cheeses, fermented meat sausages, pates and salads. PMID- 1904766 TI - [Technic of parenteral feeding]. PMID- 1904767 TI - [The artificially fed patient at home]. PMID- 1904768 TI - Isolation and characterization of the promoter region of the human intercellular adhesion molecule-1 gene. AB - We have isolated and restriction enzyme-mapped a human genomic DNA clone encompassing the first two exons and the 5' flanking sequence of the human intercellular adhesion molecule-1 (ICAM-1) gene. The transcription initiation site was identified using primer extension analysis, and 1.7 kb of DNA upstream of the transcription initiation site was sequenced. The 5' region and first exon of the ICAM-1 gene was found to be a CpG island as it was (i) (G + C)-rich with a high frequency of the dinucleotide CpG and (ii) hypomethylated irrespective of the level of ICAM-1 expression in the tissues examined. These features of the ICAM-1 promoter are similar to the promoters of many 'housekeeping' genes. However, consensus sequences for several potential regulatory elements were found in the 5'-flanking sequence, an observation in keeping with the pattern of strongly regulated ICAM-1 expression. Examination of the chromatin structure upstream of the ICAM-1 gene revealed the presence of a constitutive DNase I hypersensitive site 1.5 kb upstream of the transcription initiation site. Direct evidence that the upstream region constitutes a promoter element was demonstrated in transient transfection assays. A series of chloramphenicol acetyltransferase gene (CAT) constructs containing 5' fragments ranging in size from 1054 to 310 bp had equivalent levels of promoter activity when transfected into HeLa cells. Using a CAT construct containing a 447 bp ICAM-1 promoter fragment, we demonstrate an increase in transcription in response to interferon gamma (IFN gamma), suggesting that this proximal region of the promoter is responsible, at least in part, for IFN-gamma induction of ICAM-1 expression. PMID- 1904769 TI - Effects of interferon gamma and saponin on lymphocyte traffic are inversely related to adjuvanticity and enhancement of MHC class II expression. AB - Interferon gamma (IFN-gamma) is an effective immunological adjuvant when mixed with vaccines prior to injection, but the way in which it exerts this effect has been unclear. Because some adjuvants have been shown to affect lymphocyte traffic, and interferons have been shown to have effects on lymphocyte homing molecules, we examine in this study the effects of IFN-gamma and the potent adjuvant saponin on lymphocyte traffic, and show that both of these adjuvants increase lymphocyte homing to an injection site in mice. We have then compared effects on lymphocyte traffic and on MHC class II expression with adjuvant effects in different mouse strains. Effects on lymphocyte traffic were the inverse of adjuvant effects in different strains, however both materials enhanced MHC class II expression, and this enhancement corresponded with adjuvanticity in different strains of mice. A possible explanation for the negative effect of lymphocyte homing may be that the vast majority of T cells homing to the injection sites in response to both IFN-gamma and saponin were of the CD8+ (suppressor/cytotoxic) phenotype. PMID- 1904770 TI - Chloroquine-sensitive transplasmalemma electron transport in Tetrahymena pyriformis: a hypothesis for control of parasite protozoa through transmembrane redox. AB - Plasma membrane electron transport was studied in a protozoan cell, Tetrahymena pyriformis, by assaying transmembrane ferricyanide reduction and the reduction of iron compounds. The rates of ferricyanide reduction varied between 0.5 and 2.5 mumol/g dry wt. per min, with a pH optimum at 7.0-7.5. Other active non-permeable electron acceptors, with redox potentials from +360 to -125 mV, were cytochrome c, hexaammine ruthenium chloride, ferric-EDTA, ammonium ferric citrate, and indigo di-, tri- and tetrasulfonates. It was found that Tetrahymena cells can reduce external electron acceptors with redox potentials at pH 7.0 down to -125 mV. Ferricyanide stimulates ciliary action. Transmembrane ferricyanide reduction by Tetrahymena was not inhibited by such mitochondrial inhibitors as antimycin A, 2-n-heptyl-4-hydroxyquinoline N-oxide, or potassium cyanide, but it responded to inhibitors of glycolysis. Transmembrane ferricyanide reduction by Tetrahymena appears to involve a plasma membrane electron transport chain similar to those of other animal cells. As in other cells, the transmembrane electron transport is associated with proton release which may be involved in internal pH control. The transmembrane redox system differs from that of mammalian cells in a 20-fold greater sensitivity to chloroquine and quinacrine. The Tetrahymena ferricyanide reduction is also inhibited by chlorpromazine and suramin. Sensitivity to these drugs indicates that the transplasma membrane electron transport and associated proton pumping may be a target for drugs used against malaria, Trypanosomes and other protozoa. PMID- 1904771 TI - Physical, chemical and immunological properties of the bacterioferritins of Escherichia coli, Pseudomonas aeruginosa and Azotobacter vinelandii. AB - The 70-amino-acid-residue N-terminal sequence of the bacterioferritin (BFR) of Azotobacter vinelandii was determined and shown to be highly similar to the N terminal sequences of the Escherichia coli and Nitrobacter winogradskyi bacterioferritins. Electrophoretic and immunological analyses further indicate that the bacterioferritins of E. coli, A. vinelandii and Pseudomonas aeruginosa are closely related. A novel, two-subunit assembly state that predominates over the 24-subunit form of BFR at low pH was demonstrated. The results indicate that the bacterioferritins form a family of proteins that are distinct from the ferritins of plants and animals. PMID- 1904772 TI - Effect of dithiothreitol on the catalytic activity, quaternary structure and sulfonamide-binding properties of an extracellular carbonic anhydrase from Chlamydomonas reinhardtii. AB - Extracellular carbonic anhydrase from the unicellular green alga Chlamydomonas reinhardtii is an oligomeric protein containing subunits of 36 and 4 kDa which are joined by disulfide bonds to form higher molecular mass oligomers. In this study, the effect of dithiothreitol on some properties of the enzyme were examined. Dithiothreitol caused a 40% activation of the catalytic activity of the enzyme at low concentrations (0.1 mM), but an inactivation of about 85% of the catalytic activity at high (50 mM) concentrations. Chemical cross-linking of the enzyme with dimethyl suberimidate revealed the existence of oligomers containing up to three large subunits and at least two small subunits. Cross-linking analysis of dithiothreitol-treated carbonic anhydrase revealed that 0.1 mM dithiothreitol had no effect on the subunit composition of the enzyme, but 10 or 50 mM caused subunit dissociation, including the apparent complete dissociation of the small subunits from the large subunits. There was a characteristic enhancement of dansylamide fluorescence when this fluorescent sulfonamide bound carbonic anhydrase and the fluorescence enhancement was retained following the dithiothreitol-induced dissociation of the enzyme. These results indicate that disulfide bonds are essential for maintenance of the oligomeric structure of Chlamydomonas reinhardtii carbonic anhydrase, and that the small subunit may be necessary for enhancing catalysis, but not for the binding of sulfonamides to the enzyme. PMID- 1904773 TI - Purification and properties of two forms of ATP sulfurylase from Euglena. AB - Two forms of ATP sulfurylase have been purified to homogeneity from mitochondria (ATPSm) and cells (ATPSc) of Euglena gracilis Klebs var. bacillaris Cori (aplastidic mutant W10BSmL). Both forms are monomeric, ATPSc is 52.3 kDa and ATPSm is 55 kDa. The pI is 7.9 for ATPSc and 5.8 for ATPSm. Therefore, ATPSm binds to DEAE-cellulose at pH 7.4; ATPSc does not. After cleavage by CNBr, the two forms of ATP sulfurylase show different sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) patterns, suggesting that they differ in amino acid sequence. ATPSm is mainly associated with the mitochondrial membrane and ATPSc is mainly soluble in the cells. Both enzymes require similar conditions in the molybdolysis assay, but show different pH optima when sulfate is used as substrate. ATPSc is more sensitive to adenosine 5'-phosphosulfate (APS) inhibition than ATPSm in the SO2-4 incorporation reaction. In the reverse reaction, ATPSc requires much higher concentrations of PPi and MgCl2 to saturate the reaction than ATPSm. The data indicate that the two enzymes are quite distinct and may have different roles in cell metabolism. PMID- 1904774 TI - Phospholipid composition of rat megakaryocytes and its rearrangement in platelets. AB - Rat platelets and their megakaryocyte precursors were examined for phospholipid composition. (1) The phospholipid composition of rat megakaryocytes, which were enriched and prepared from bone marrow cells, was almost identical to that of platelets. (2) The subclass composition of choline-containing glycerophospholipids (CGP) of rat megakaryocytes differed significantly from that of platelets: 1-alkenyl-2-acyl glycerophosphocholine (GPC) in megakaryocytes accounted for 29% of the total, whereas that in platelets was only 7%. (3) Rat platelets contained a larger amount of arachidonic acid than megakaryocytes, especially in ethanolamine-containing glycerophospholipids (EGP). (4) [32P]Phosphoric acid was significantly incorporated into megakaryocytes, whereas platelets showed little incorporation. On the other hand, the uptake of [3H]arachidonic acid into platelet phospholipids was about 15-times higher than that observed with megakaryocytes. (5) As reported previously for other blood cells, such as neutrophils and macrophages, the radioactivity of labeled arachidonic acid incorporated into CGP of platelets decreased, whereas that incorporated into EGP increased during a subsequent chase period. Hardly any such change was observed with megakaryocytes. These results suggest that the phospholipid composition of rat platelets is mainly determined at the time of thrombopoiesis, whereas the composition of molecular species is remodeled during circulation after thrombopoiesis. PMID- 1904775 TI - Lipid peroxidation, protein thiol oxidation and DNA damage in hydrogen peroxide induced injury to endothelial cells: role of activation of poly(ADP ribose)polymerase. AB - These experiments are a continuation of work investigating the mechanism of oxidant-induced damage to cultured bovine pulmonary artery endothelial cells (BPEC). Earlier experiments implicated DNA strand breakage and activation of poly(ADP-ribose)polymerase as critical steps in cell injury. In the current report, a better defined model of oxidant stress was used to investigate DNA damage, lipid peroxidation and protein thiol oxidation in BPEC following oxidant stress. The dose and time response of LDH release following exposure to H2O2 were established. H2O2 was metabolized rapidly by BPEC (t1/2 = 20 min). Hydrogen peroxide-induced increases in thiobarbituric acid (TBA) reactive material were prevented by pretreatment with the lipophilic antioxidant diphenylphenylinediamine (DPPD). However, DPPD did not decrease LDH release. Conversely, pretreatment with 5 mM 3-aminobenzamide (3AB), a competitive inhibitor of poly(ADP-ribose)polymerase, prevented LDH release from BPEC following H2O2 treatment. Dithiothreitol (DTT), a sulfhydryl reducing agent, also prevented LDH release. The effects of 3AB and DTT on H2O2-induced changes in DNA strand breaks and NAD+ and ATP levels were investigated as well as the effect of H2O2 on soluble and protein-bound thiols. As DPPD inhibited peroxidation without preventing LDH release, lipid peroxidation does not appear to play a role in the loss of BPEC viability in response to oxidant stress. As protein thiol oxidation was not caused by H2O2, it does not appear to play a causative role in cytotoxicity, although DTT may protect via maintenance of soluble thiols. H2O2 induces DNA strand breaks, which activate poly(ADP-ribose)polymerase, leading to depletion of cellular NAD+ and ATP and loss in cell viability. This supports earlier studies implicating the activation of poly(ADP-ribose)polymerase in oxidant injury to cultured endothelial cells. PMID- 1904776 TI - Hyaluronic acid synthesis is absent in normal human endothelial cells irrespective of hyaluronic acid synthetase inhibitor activity, but is significantly high in transformed cells. AB - The characteristics of glycosaminoglycan (GAG) synthesis in normal and transformed human endothelial cells were analyzed by the incorporation of [3H]glucosamine and by the activities of GAG synthetases. The GAG synthesized by normal endothelial cells consisted of mainly heparan sulfate (HS) and chondroitin sulfate/dermatan sulfate but little hyaluronic acid (HA) (less than 1%). The characteristics of GAG synthesis by normal cells reflected the synthetic enzyme activities for each individual GAG: the activity of HA synthetase was very low. In spite of this, the activity of HA synthetase inhibitor, induced in growth retarded fibroblasts with low HA synthetase activity (Matuoka et al. (1987 J. Cell Biol., 104, 1105-1115), was very low in endothelial cells. In contrast to normal cells, transformed endothelial (ECV304) cells synthesized mainly HA (62% of total GAGs). These findings suggest that the regulatory system of GAG metabolism is cell type specific, and that transformation is accompanied by high levels of HA synthesis in endothelial cells. PMID- 1904777 TI - 19F-NMR study of the effect of lead on intracellular free calcium in human platelets. AB - Lead has been shown to affect calcium homeostasis. However, there is no prior evidence to indicate an effect of low concentrations of lead in the environment (approximately 1 microM) on the intracellular free Ca2+ concentration in any human tissue. We have investigated the effect of lead on the intracellular free Ca2+ concentration of human blood platelets using 19F-NMR and a fluorinated intracellular Ca2+ indicator. We report a basal intracellular free Ca2+ value of 172 +/- 8 nM. Treatment with 1, 5, 10 and 25 microM Pb2+ resulted in average increases in intracellular free Ca2+ of 39%, 91%, 135% and 172%, respectively. The percent increase in intracellular free Ca2+ was linearly and positively correlated with the log of Pb2+ concentration. Using atomic absorption spectroscopy, a significant increase in total calcium of approx. 10 nmol/mg protein was found in 25 microM Pb2+ treated platelets. This indicates that influx of external Ca2+ contributes to the observed increase in free Ca2+. The results provide an explanation for the previously reported effects of lead on platelet function, and suggest a mechanism for low level lead-induced hypertension. PMID- 1904778 TI - Bombesin stimulates a high affinity GTPase activity in membranes of Swiss 3T3 fibroblasts. AB - Peptides of the bombesin family are mitogenic for Swiss 3T3 fibroblasts and in these cells stimulate the turnover of polyphosphoinositides. Recent studies have suggested that G protein(s) may be involved in the signal transduction pathway triggered by bombesin. In this study we have found and characterized a high affinity GTPase activity stimulated by bombesin in membranes of Swiss 3T3 fibroblasts. Our results support the involvement of a G protein in the response of Swiss 3T3 cells to bombesin. PMID- 1904779 TI - Blood coagulation and fibrinolysis during normal pregnancy. AB - Fifty-six pregnant women (gestational age 6-40 weeks) were evaluated for their coagulation activation (fibrin monomers and thrombin-antithrombin III complex) and for their fibrinolysis profile by determining tissue plasminogen activator, plasminogen activator inhibitor, plasminogen, alpha 2-antiplasmin and D-dimer. Fibrin monomers and thrombin-antithrombin III complexes were found to be significantly increasing with gestational age. All the fibrinolytic parameters showed a steady growth with the progress of the pregnancy, with the exception of tissue plasminogen activator which showed a significant decrease with gestational age, but mainly within the reference range. These results suggest a stimulation of the coagulation system and an activation of fibrinolysis with ongoing pregnancy, although the increasing alpha 2-antiplasmin and plasminogen levels and the decreasing tissue plasminogen activator concentrations do not conform to this trend. PMID- 1904780 TI - Composition of proteoglycan fragments from hyaline cartilage produced by granulocytes in a model of frustrated phagocytosis. AB - An in vitro model of frustrated phagocytosis was developed in which granulocytes interact with well-defined slices of hyaline cartilage. The composition of the purified proteoglycan fragments released from the cartilage slices by N-formyl methionyl-leucyl-phenylalanine-stimulated granulocytes was studied after 30, 60 and 90 min incubation time. It was shown that the proteoglycan fragments do not change their composition during incubation. The only change observed during incubation was an increase in the quantity of the fragments. The protein content of the proteoglycan fragments is 7.0-8.6%, corresponding to a peptide chain of 24 28 amino acids, and the relative molecular mass of the total fragment is Mr = 37,600-39,200. On average, each proteoglycan fragment contains two chondroitin sulphate chains (Mr = 22,000-22,400), every fourth fragment contains a keratan sulphate chain (Mr = 7000-7200) and every seventh to eighth contains an O glycosidic oligosaccharide, whereas no N-glycosidic oligosaccharide could be detected. The results of the disaccharide analysis show that the galactosaminoglycan chains contain 76.2-83.6% chondroitin 4-sulphate, 12.9-19.4% chondroitin 6-sulphate, 3.5-3.8% chondroitin and no dermatan sulphate. Since composition and relative molecular mass of the chondroitin sulphate and keratan sulphate chains from the proteoglycan fragments resemble those of native proteoglycans, the conclusion may be drawn that the degeneration of the proteoglycans occurs by proteases that attack preferably the chondroitin sulphate rich region of the core protein. This is the first inflammation model of joint destruction, which demonstrates the elution of soluble specific proteoglycan degradation products of defined size. PMID- 1904781 TI - Hyperventilation-induced panic attacks in panic disorder with agoraphobia. AB - Eight minutes of hyperventilation to an end-tidal PCO2 of less than 20 mmHg led to a panic attack in 7 of 12 patients with panic disorder with agoraphobia and only 1 of 12 normal controls. Patients experienced greater increases in panic symptoms than controls during hyperventilation. Patients who reported more distress from somatic symptoms of hyperventilation during the preceding week were more likely to panic during hyperventilation. Patients who panicked during hyperventilation exhibited a delayed recovery of normocapnia following hyperventilation. Hyperventilation by this protocol is an effective means of inducing panic attacks in the laboratory. A hyperventilation challenge may identify a subgroup of patients for whom hyperventilation symptoms are frequently associated with panic. PMID- 1904782 TI - Lithium carbonate augmentation of desipramine and fluoxetine in refractory depression. PMID- 1904783 TI - Fluorescence measurements of immune complexes of Mab 4-4-20 with isomeric haptens. AB - Relative differences in the active site environment of a monoclonal antibody when covalently bound to two isomeric haptens were studied using fluorescence quenching and lifetime measurements. Murine monoclonal antibody 4-4-20, a well characterized high affinity antifluorescein antibody, served as the model IgG protein. Isomeric haptenic probes comparatively studied were fluorescein-5 isothiocyanate (FITC I, the immunogen) and fluorescein-6-isothiocyanate (FITC II). In kinetic binding studies, the association rate for the interaction of 4-4 20 with FITC I was greater than 2,000 times faster than the reaction with FITC II. Fluorescence lifetimes for FITC I covalently bound to 4-4-20 were 3.89 ns and 0.37 ns, indicative of hapten bound outside and inside the active site, respectively. Fluorescence lifetime for FITC II within the active site was indistinguishable from bound FITC I, indicating that interactions with active site residues which resulted in a decreased lifetime were similar for both isomers. A decreased lifetime for active site bound FITC I was consistent with the 90-95% quenching of fluorescein fluorescence. Dynamic fluorescence quenching experiments with iodide and FITC I in the active site showed no solvent accessibility, whereas bound FITC II showed significant accessibility. These results suggest that the difference in bond angle which accompanies binding of isomer II relative to isomer I within the active site probably leads to steric constraints resulting in a more open configuration of the 4-4-20 active site. PMID- 1904784 TI - The New York Academy of Medicine: prospects and opportunities. PMID- 1904785 TI - Technology-dependent children in New York State. AB - A survey in New York State revealed 210 medically stable technology-dependent children retained inappropriately in acute-care hospitals. They remained in hospitals primarily because of a shortage of skilled home nursing services in the communities where they lived, family problems that prevented their care at home, and a shortage of beds in appropriate skilled nursing facilities. Most of the children were younger than one year of age, most had disorders of the central nervous system or respiratory system, and most needed respiratory support. The average child needed more than 13 hours of skilled nursing care per day. With adequate nursing services, many of these children could be cared for in their homes. For some, family care was not feasible because of social, psychological, and economic problems. To make it possible to care for medically stable technology-dependent children most effectively, we must develop additional community-based resources. Home nursing services of the highly skilled kind needed to care for them are in short supply today in New York State. There is a shortage of beds in extended care nursing facilities capable of caring for them, especially for infants and very young children. There is a shortage of the other supportive social services needed by families who attempt to care for them at home. Until we address these needs and develop these services, technology dependent children medically appropriate for care outside acute-care hospitals will be forced to remain hospitalized, to the detriment of the children and their families. PMID- 1904786 TI - Ig CH and D14S1 variants in rheumatoid arthritis--linkage and association studies. AB - We have looked for an effect of 14th chromosomal genes linked to immunoglobulin heavy chain (IgCH) or D14S1 regions on susceptibility to rheumatoid arthritis (RA) by both linkage (sibling pair analysis) and association studies. There was no overall linkage between RA and either IgCH or D14S1. However, Gm haplotype similarity in affected siblings appeared greater in either DR4-positive as compared to DR4-negative sibships or in sibships without clinical or serological evidence of autoimmune thyroid disease when compared to sibships with such evidence. In association studies there were no associations at the D14S1 locus. Within the Ig CH region there were no overall associations. However, within the RA population G1m (z) and G3m (g) both appeared less frequent in DR4-negative RA versus both DR4-positive RA and versus control groups. Analysis of DNA variants at Ig CH loci showed differences at the gamma 4 locus with a 9.0 kb fragment appearing less frequently in DR4-positive RA versus DR4-negative RA and control groups. The results suggest a weak or HLA-DR dependent effect of genes linked to the Ig CH region on susceptibility to RA. PMID- 1904787 TI - Haemarthrosis associated with thrombolytic therapy. PMID- 1904788 TI - High perfusate PO2 impairs thermosensitivity of hypothalamic thermosensitive neurons in slice preparations. AB - The thermosensitivity of neurons in the preoptic area (POA) of guinea pigs was examined in slice preparations during perfusion with artificial cerebrospinal fluid (ACSF) gassed with 95% O2/5% CO2 (95% O2-ACSF) or 21% O2/5% CO2/74% N2 (21% O2-ACSF). Perfusate PO2, PCO2, and pH of 95% O2-ACSF measured in the incubation chamber were, respectively, 402.9 mmHg, 39.1 mmHg, and 7.38; those of 21% O2-ACSF were 154.0 mmHg, 33.1 mmHg, and 7.41. All the thermosensitive neurons (n = 6) originally identified during perfusion with 95% O2-ACSF also exhibited their thermosensitivity when examined again in 21% O2-ACSF. However, 63% of the thermosensitive neurons (n = 8) originally identified with 21% O2-ACSF lost their thermosensitivity in 95% O2-ACSF. The addition of superoxide dismutase to 95% O2 ACSF prevented the loss of thermosensitivity in 88% of the neurons (n = 8). These results suggest that oxygen toxicity due to free radical formation may account for the impairment of neuronal thermosensitivity in 95% O2-ACSF. PMID- 1904790 TI - Preferential feeding behaviour of hens in different gaseous atmospheres. AB - 1. The object of this study was to identify the concentrations of carbon dioxide (CO2) and hypoxia (induced by argon) which hens could detect and by preference avoid. 2. Hens were housed in an apparatus consisting of an upper roosting chamber connected to two descending passages which led to separate identical feeding chambers. The gas concentration in both these feeding chambers could be regulated. 3. The hens were allowed to feed in either a normal air atmosphere or an altered atmosphere containing a sub-stunning concentration of CO2 or argon. The birds' preference for feeding in the two chambers was used as an indicator of the concentration which they chose to avoid. 4. The study involved two experiments. In the first it was found that when the concentration of CO2 was raised above 5%, or the concentration of oxygen was reduced to 10% or below, the occupancy of that chamber was significantly reduced. 5. The results of the second experiment confirmed that a concentration of above 7.5% CO2 or oxygen levels of 10% or below can be detectable to hens and, given a free choice, the hens learnt to avoid such atmospheres. 6. The presence of a dominant bird in the roosting chamber or in the feeding chamber containing air caused the subordinate birds to enter the treatment chamber containing gas. This would imply that the unpleasantness of the stunning gases at the concentrations used in this study was less severe than the social pressure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1904789 TI - Air hygiene in a pullet house: effects of air filtration on aerial pollutants measured in vivo and in vitro. AB - 1. The natural history of air hygiene in a pullet house was assessed at three weekly intervals using a combination of in vitro and in vivo assays. The performance of an internal air filter was also examined as an experimental technique for providing clean air. 2. Overall, air hygiene was poor by comparison with occupational standards for human health. The mass concentrations of respirable and inspirable dust were 1.4 and 11.3 mg/m3 compared to human exposure limits of 5 and 10 mg/m3 respectively. The concentration of ammonia was typically about 20 ppm. 3. The majority (greater than 99%) of airborne particles were non viable. Commensal bacteria from the skin were the most numerous airborne bacteria. Scopulariopsis and Aspergillus spp. were the most prevalent fungi recovered from the air and bird's lungs respectively. The concentrations of airborne and lung fungi were positively correlated with ammonia concentrations. 4. The differences between in vivo and in vitro assays of airborne microorganisms suggest that an aerosol sampler should be devised which better mimics the physical and biochemical environment of the respiratory tract. PMID- 1904791 TI - Infections and sepsis in disasters. AB - It seems reasonable to expect that infections will occur after certain types of disasters. There are some data to support this conjecture in studies of tornadoes, hurricanes, and mass trauma situations. We have tried to extrapolate from these data what we believe will be the infectious effects of different types of disasters, taking into account the potential for alteration in the host secondary to injury, the modification of living conditions, and the possibility of the disruption of medical care. PMID- 1904792 TI - Nutritional and metabolic support. AB - The problem of hunger accompanies any mass casualty situation that results in large numbers of patients with traumatic and burn injuries complicated by sepsis and end organ failure. This is caused by the inability of many of these patients to eat. Such patients require artificial nutrition. A rescue operation that does not provide adequate artificial nutrition, no matter how well organized with respect to field stabilization, surgical intervention, and intensive care, will find many of its patients dying of multiorgan disorders due to nutritional failure. This article is concerned with how to provide such artificial nutrition. PMID- 1904793 TI - Evaluating nonpharmacologic treatment of ventricular tachycardia. PMID- 1904794 TI - High-energy proton beam radiation therapy for gynecologic malignancies. Potential of proton beam as an alternative to brachytherapy. AB - Fifteen patients with advanced gynecologic malignancies were treated with high energy proton beam radiation therapy (RT) at the Particle Radiation Medical Science Center (PARMS), Tsukuba University, Japan, from 1983 to 1987. The potential of proton beam RT as an alternative to conventional brachytherapy was evaluated. Except for one local recurrence, 14 of 15 patients were locoregionally controlled for 15 to 57 months. Two-year local control rate and 2-year survival rate were 92.3% and 93.3%, respectively. Two cases of transient, radiation induced proctitis (neither of which required surgical treatment) were the only complications despite a target dose that exceeded 8000 cGy in most cases. The results suggest that sharply localized, high-dose proton beam RT can produce an antitumor effect equivalent to that of conventional brachytherapy. PMID- 1904795 TI - Personhood. PMID- 1904796 TI - Inhibitory effects of new types of biflavonoid-related polyphenols; lophirone A and lophiraic acid, on some tumor promoter-induced biological responses in vitro and in vivo. AB - Lophirone A, isolated as a new type of biflavonoid-related inhibitor of Epstein Barr virus (EBV) activation, was tested for further inhibitory properties against tumor promotion by short-term system. Lophirone A (200 micrograms) significantly inhibited inflammation of mouse ear (inhibitory effect (IE) = 70%) by 12-O hexadecanoyl-16-hydroxyphorbol-13-acetate (HHPA, 2 micrograms). It also inhibited both Ca(2+)- and phospholipid-dependent protein kinase C (PKC) activation by 12-O tetradecanoylphorbol-13-acetate (TPA, IC50 = 50 microM). Application of lophirone A (160 nmol) reduced the number of tumors per mouse (IE = 85%) in an initiation promotion experiment using dimethylbenz[a]anthracene (DMBA, 0.19 mumol) and TPA (1.6 nmol) on ICR mouse skin. Lophiraic acid, a related polyphenol, was negative in all of the short-term tests. An important chemical factor which may reduce the activities of flavonoid class of inhibitors for tumor promotion was indicated. PMID- 1904797 TI - Enhanced poly ADP-ribosylation in human leukemia lymphocytes and ovarian cancers. AB - Freshly isolated human peripheral blood lymphocytes from leukemia (AML, ALL, CML) subjects, showed a 2.5-3.5-fold increase in the poly ADPR transferase (poly ADPRT) activity whereas ovarian cancers showed a 2-fold increase. This was accompanied by a drop in NAD levels of 45%-63% in leukemia cells and 40% in ovarian cancers. Tumour promoters phorbol-12-myristate-13-acetate (PMA) and mezerein produced an increase in poly ADPRT activity in both normal and CML lymphocytes, but the increase was more marked in the case of normals. This was accompanied by a drop in NAD levels. The results presented show a marked increase in poly ADP-ribosylation in malignant cells but normal lymphocytes showed a greater response to tumour promoters as compared to CML lymphocytes. PMID- 1904798 TI - Continued contact lens wear in patients with giant papillary conjunctivitis. AB - We performed a six-year retrospective evaluation of 47 contact lens patients with a documented history of giant papillary conjunctivitis (GPC). The relationships between specific symptoms, contact lens history, treatment regimens, and clinical responses were studied. Specifically, we sought to determine the number of patients forced to discontinue contact lens wear due to GPC. Our study indicated two important preconditions to be associated with the onset of symptoms: the continued use of aging lenses and suboptimal lens care. For those patients treated and followed-up for at least 4 months, 79% obtained total resolution of their symptoms. Though the numbers are too small to make any significant conclusions about treatment methods it seems that lens discontinuance alone does not appear to be an adequate treatment for this condition and may serve better as adjunct to other therapy. PMID- 1904799 TI - kappa/lambda index for confirming urinary free light chain in amyloidosis AL and other plasma cell dyscrasias. AB - Primary systemic amyloidosis (AL), a disease involving the deposition of immunoglobulin light chains in tissue, is caused by a plasma cell dyscrasia. In the case of amyloidosis reported here, no monoclonal component was seen upon routine protein electrophoresis of serum or urine nor was a bone marrow analysis positive for AL. Immunofixation electrophoresis did not show a typical paraprotein band but did show, in the gamma region, two large diffuse bands and a lower concentration of oligoclonal-type bands, all of which stained for free lambda but not for free kappa chain. The ratio of kappa to lambda chains in urine was 0.178, much less than the ratio in serum (1.3). Six other urine samples from a group of patients with documented Bence Jones proteinuria also exhibited kappa/lambda ratios that differed manyfold from the ratios in their corresponding serum samples. On the other hand, the kappa/lambda ratios from seven controls (seven patients with generalized proteinuria unrelated to plasma cell dyscrasia) were similar in serum and urine. This difference between the kappa/lambda ratios from serum and urine can be expressed as a kappa/lambda index. The index was significantly different (P less than 0.01) between the two patient groups compared here, and was useful in confirming the presence of Bence Jones protein in this case with a difficult-to-interpret electrophoretic pattern. Although the kappa/lambda ratio has been widely used for confirmation and identification of monoclonal components in serum, its use in clinical laboratories has not been widely extended to urine. Comparison of serum and urine kappa/lambda ratios as a kappa/lambda index may help reduce the need for more complex immunoelectrophoresis techniques in identifying free light chains in urine. PMID- 1904800 TI - Influence of low-density-lipoprotein particle size on measurement of apolipoprotein B. PMID- 1904801 TI - Enzymatic fluorometric procedure for phospholipid quantification with an automated microtiter plate fluorometer. AB - We describe a new enzymatic assay for phospholipids that is rapid, sensitive, convenient, and inexpensive. The method is based on the fluorometric detection of H2O2, generated by the choline oxidase-catalyzed oxidation of choline, after liberation of choline from phospholipids by phospholipase D. Significant advantages over existing methods are that the entire reaction sequence can take place in a single vessel, a 12 x 8 well microtiter plate, and that the fluorescence intensity can be measured automatically with a Fluoroskan II (Labsystems Oy) detector. Extracting samples with organic solvents is unnecessary, although the method can be applied to extracts in isopropanol. The assay is approximately 60-fold more sensitive and has a limit of detection eightfold lower than currently available enzymatic colorimetric methods. Including solvent blanks, eight standards, and three quality-control pools, 34 samples can be pipetted and assayed in duplicate in 60 min. Results obtained by this procedure for total phospholipid choline in lipoproteins in primate plasma agreed well with those obtained for inorganic phosphorus by the Bartlett acid digestion procedure. PMID- 1904802 TI - Measurement of serum Apo A1 and Apo B: comparison of immunoturbidimetric and rate nephelometric techniques. PMID- 1904803 TI - An enzyme immunoassay for determining total thyroxine in human serum using an ultramicroanalytical system. AB - A simple, rapid competitive ultramicroElisa assay has been developed for the measurement of total thyroxine (T4) using only 10 microliters of serum. Our novel UME is based on fluorescence measurements of the hydrolytic product of 4-methyl umbelliferyl-beta-D-galactopyranoside. T4-beta-Galactosidase conjugates and monoclonal antibodies were immobilized on polyvinyl plates, with sodium salicylate used as a blocking agent for thyroxine binding protein. The analytical steps were carried out using a semiautomated batch-assay system entitled "SUMA" (system for ultramicroanalysis). The T4 assay was completed in 2 h, with a measuring range of 24-386 nmol/L. The intra-assay coefficient of variation (CV) was 4.6-6.9% and the inter-assay C.V. 9.0-12.4% depending on the T4 concentrations. Percentage recovery ranged from 99.2-111%. Regression analysis showed a good correlation with an established radioimmunoassay (n = 121, r = 0.946, P less than 0.01). PMID- 1904804 TI - Intact parathyroid hormone assay is superior to mid region assay in the EDTA infusion test in hyperparathyroidism. AB - We examined the use of an intact parathyroid hormone two-site immunoradiometric assay compared with a mid region parathyroid hormone radioimmunoassay in ethylene diamine tetraacetic acid-infusion test in 15 patients with hyperparathyroidism. During the test, plasma intact parathyroid hormone levels increased by 240 +/- 43%, whereas the plasma levels of mid molecule parathyroid hormone increased by only 65 +/- 17%, which is significantly lower (P less than 0.01). Four patients had no increase in plasma mid molecule parathyroid hormone level but still a large increase in plasma intact parathyroid hormone level (P less than 0.01). Thus, plasma measurement of intact parathyroid hormone is superior to that of mid molecule parathyroid hormone in the ethylene diamine tetraacetic acid-infusion test in patients with hyperparathyroidism. PMID- 1904805 TI - Parenteral nutrition in the thermally injured patient. PMID- 1904807 TI - AADE guidelines. Infection control guidelines for patient education as a means of preventing blood-borne disease transmission during diabetes self-care procedures. AB - There exists a potential for blood-borne disease transmission with many diabetes self-care behaviors. It is necessary for the diabetes educator to instruct the patient regarding infection-control practices. PMID- 1904806 TI - Caries-preventive effect on primary and permanent teeth and cost-effectiveness of an NaF tablet preschool program. AB - The aim was to assess restorative care, approximal caries, and cost-effectiveness in children at the ages of 8 and 17 yr in relation to NaF tablet intake between 1/2 and 7 yr of age. Based on interview data, 304 subjects (born 1967 in Lund, Sweden) were divided into five groups with different periods of consumption and one group with no intake. A statistically significant difference was found in fs at 8 yr (P less than 0.001) and in FS at 17 yr (P less than 0.01) between children who had taken the tablets regularly from the first year of life to age 5 7 yr (fs = 1.9; FS = 3.8) and the non-consumers (fs = 5.2; FS = 5.9). In the other four tablet groups, both the fs and the FS values tended to decrease with increasing duration of intake. The prevalence of approximal caries also tended to decrease, as regards both dfs and DFS, increasing duration of tablet consumption, with an statistically significant difference (P less than 0.001) in primary teeth between children with the longest intake (dfs = 1.4) and non-consumers (dfs = 4.9). The cost-effectiveness ratio was approximately 1:1 for both dentitions. Most of the effect was obtained in the primary dentition. PMID- 1904808 TI - Diabetes educators encourage safe needle practice. AB - Diabetes educators should lead individuals and communities in recommended needle disposal practice, not only to promote safety but also to advocate the right of persons with diabetes to be disassociated from the fear of infectious disease prevalent in today's society. PMID- 1904810 TI - Managing the greenhouse problem. PMID- 1904809 TI - Promotion of mouse lung tumors by bioaccumulated polychlorinated aromatic hydrocarbons. AB - Lung tumors initiated in infant Swiss mice by N-nitrosodimethylamine (NDMA) were promoted by a single dose of a mixture of polychlorinated biphenyls (PCBs), Aroclor 1254 (250 or 500 mg/kg) given 4 days later. The tumors were typical alveologenic adenomas, and their number increased gradually over the course of 1 year to a maximum 4-fold enhancement in average tumor number compared with those given NDMA alone. The time course pattern suggested continuous tumor stimulation by the nonmetabolized PCB congeners retained in the tissues. Content of the nine major bioretained PCB congeners in carcass, liver, and lung was determined at intervals after treatment. Several showed tissue-specific retention patterns: 2,3,3',4,4'-PCB was selectively retained in lung and liver, and 2,2',3,4,4', 5' HCB in lung. In tests of the tumor-promoting ability of individual congeners, the 2,2',3,4,4',5'-HCB, an Ah receptor agonist, promoted lung tumors when given singly, whereas another prominent bioretained congener, the 2,2',4,4',5,5'-HCB, an Ah receptor antagonist, did not promote, and in fact abrogated the positive effect of the 2,2',3,4,4',5'-HCB. In a parallel examination of persistent biochemical effects, a single low dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin (5 nmole/kg) resulted in significant elevation of immunochemically detected protein and enzymatic activity of cytochrome P450 IA1 in lung for at least 12 weeks; these parameters were elevated for at least 30 weeks after a single dose of Aroclor 1254 (500 mg/kg). Taken together these results suggest that Ah-receptor dependent induction of cytochrome P450 IA1 in mouse lung is correlated with and possibly causally involved in promotion of tumors by retained congeners. PMID- 1904811 TI - Concentrations of organic contaminants in mollusks and sediments at NOAA National Status and Trend sites in the coastal and estuarine United States. AB - Mean concentrations of PAHs, PCBs, and DDT in mollusks and sediments at sites in the National Status and Trends Program (NST) are distributed in log-normal fashion. The dry weight-based chlorinated organic concentrations in mollusks generally exceed those in nearby sediments by an order of magnitude. PAHs are found at similar concentrations in sediments and mollusks. Highest concentrations of PCBs and DDT in mollusks are in the ranges of 1000 to 4000 ng/g (dry) and 400 to 1000 ng/g (dry), respectively. The highest PAH concentrations in sediments are in the 10,000 to 50,000 ng/g (dry) range. While higher concentrations of contaminants can be found by sampling localized hot spots, the NST data represent the distribution of concentrations over general areas of the coastal United States. PMID- 1904812 TI - Biogeochemical processes governing exposure and uptake of organic pollutant compounds in aquatic organisms. AB - This paper reviews current knowledge of biogeochemical cycles of pollutant organic chemicals in aquatic ecosystems with a focus on coastal ecosystems. There is a bias toward discussing chemical and geochemical aspects of biogeochemical cycles and an emphasis on hydrophobic organic compounds such as polynuclear aromatic hydrocarbons, polychlorinated biphenyls, and chlorinated organic compounds used as pesticides. The complexity of mixtures of pollutant organic compounds, their various modes of entering ecosystems, and their physical chemical forms are discussed. Important factors that influence bioavailability and disposition (e.g., organism-water partitioning, uptake via food, food web transfer) are reviewed. These factors include solubilities of chemicals; partitioning of chemicals between solid surfaces, colloids, and soluble phases; variables rates of sorption, desorption; and physiological status of organism. It appears that more emphasis on considering food as a source of uptake and bioaccumulation is important in benthic and epibenthic ecosystems when sediment associated pollutants are a significant source of input to an aquatic ecosystem. Progress with mathematical models for exposure and uptake of contaminant chemicals is discussed briefly. PMID- 1904813 TI - A rapid and economical method for hybrid purity testing of tomato (Lycopersicon esculentum L.) F1 hybrids using ultrathin-layer isoelectric focusing of alcohol dehydrogenase variants from seeds. AB - In the cultivated tomato (Lycopersicon esculentum L.), two electrophoretic variants of the enzyme alcohol dehydrogenase (ADH) encoded by the alleles Adh-1+ and Adh-1(1) are found. A rapid and economic method for testing the hybrid purity of tomato F1 seeds, based on the expected presence of Adh-1 alleles, was developed. The method is based on the analysis of the ADH variants by ultrathin layer isoelectric focusing, pH range 3-10, of crude extracts from imbibed seeds, followed by enzyme activity staining. The isoelectric points (pI's) of the ADH variants were estimated to be 5.5 and 5.7 for Adh-1+ and Adh-1(1), respectively. Using the procedure described and a newly developed sample applicator strip, it is possible for one person to routinely analyze 1152 seeds per day using only a single electrophoresis unit. An investigation of a large number of inbred lines, both experimental and commercial hybrids, together with open-pollinated varieties, showed the potential of the method. Among F1 hybrids, a higher frequency of the Adh-1(1) allele was found than among open pollinated varieties, suggesting that F1 hybrid breeding has resulted in a higher frequency of Adh-1(1) alleles by selection of linked genes. PMID- 1904814 TI - Resolving isoforms of aldose reductase by preparative isoelectric focusing in the Rotofor. AB - We have resolved and characterized isoforms of aldose reductase from bovine and porcine lenses by preparative isoelectric focusing with narrow pH gradients using the Rotofor. Both bovine and porcine lens aldose reductases were resolved as two enzyme isoforms. The bovine isoforms were Mr40400 +/- 445 polypeptides of pI4.71 and 5.19. Porcine isoforms were Mr41500 +/- 450 polypeptides of pI 4.90 and 5.30. Staphylococcus aureus V-8 protease digestion patterns for each set of isoforms were essentially identical and all isoforms probably contain blocked amino terminal amino acids. Antiserum to bovine lens aldose reductase cross-reacted with porcine lens aldose reductase. Each isoform displayed substrate preferences characteristic of mammalian aldose reductases. With purification, both bovine and porcine lens aldose reductases became less sensitive to inhibition by 6-fluoro spiro-(chroman-4.4'-imidazolidine)-2',5'-dione (sorbinil). PMID- 1904815 TI - Polyacrylamide gel electrophoresis of reducing saccharides labeled with the fluorophore 8-aminonaphthalene-1,3,6-trisulphonic acid: application to the enzymological structural analysis of oligosaccharides. AB - Mono- and oligosaccharides, each containing a reducing end group, were labeled with the charged fluorophore 8-aminonaphthalene-1,3,6-trisulphonic acid and the resulting derivatives were separated with high resolution by polyacrylamide gel electrophoresis using a method developed recently (P. Jackson, Biochem. J. 1990, 270, 705-713) but with an alternative electrophoretic buffer system. The fluorescent derivatives of glucose and all its straight chain, alpha 1-4 linked, oligomers from maltose to maltoheptaose were well resolved. Various isomers such as maltose and lactose could be separated, as were maltose and cellobiose and some epimers, for instance glucose and galactose. The method was applied to the analysis of the partial sequential degradation of a complex oligosaccharide with neuraminidase and beta-galactosidase. Gels showing fluorescent saccharide band patterns were recorded in picomolar quantities either photographically or using an imaging system based on a cooled charge-coupled device. PMID- 1904817 TI - Structural and functional differences between carbonic anhydrase isoenzymes I and II as studied by site-directed mutagenesis. AB - Site-specific mutagenesis has been used to replace amino acid residues in the active site of human carbonic anhydrase II with residues characterizing carbonic anhydrases I. Previous studies of [Thr200----His]isoenzyme II [Behravan, G., Jonsson, B.-H. & Lindskog, S. (1990) Eur. J. Biochem. 190, 351-357] showed that His200 is important for the specific catalytic properties of isoenzymes I. In this paper some properties of two single mutants, Asn62----Val and Asn67----His, as well as a double mutant, Asn67----His/Thr200----His, are described. The results show that neither Val62 nor His67 give rise to isoenzyme-I-like properties, while the double mutant behaves like the single mutant with His200. At pH 8.9, the variant with Val62 has a higher value of kcat/Km for CO2 hydration than unmodified isoenzyme II, whereas the variant with His67 has an enhanced kcat value. The replacement of Asn62 with Val results in a 20% increase of the 4 nitrophenyl acetate hydrolase activity. For the double mutant, the esterase activity is quite close to that calculated on the assumption that the effects of the two single mutations on the free energy of activation are additive. PMID- 1904816 TI - Site directed mutagenesis of the heme axial ligands of cytochrome b559 affects the stability of the photosystem II complex. AB - Cytochrome (cyt) b559, an integral membrane protein, is an essential component of the photosystem II (PSII) complex in the thylakoid membranes of oxygenic photosynthetic organisms. Cyt b559 has two subunits, alpha and beta, each with one predicted membrane spanning alpha-helical domain. The heme cofactor of this cytochrome is coordinated between two histidine residues. Each of the two subunit polypeptides of cyt b559 has one His residue. To investigate the influence of these His residues on the structure of cyt b559 and the PSII complex, we used a site directed mutagenesis approach to replace each His residue with a Leu residue. Introduction of these missense mutations in the transformable unicellular cyanobacterium, Synechocystis 6803, resulted in complete loss of PSII activity. Northern blot analysis showed that these mutations did not affect the stability of the polycistronic mRNA that encompasses both the psbE and the psbF genes, encoding the alpha and the beta subunits, respectively. Moreover, both of the single His mutants showed the presence of the alpha subunit which was 1.5 kd smaller than the same polypeptide in wild type cells. A secondary effect of such a structural change was that D1 and D2, two proteins that form the catalytic core (reaction center) of PSII, were also destabilized. Our results demonstrate that proper axial coordination of the heme cofactor in cyt b559 is important for the structural integrity of the reaction center of PSII. PMID- 1904818 TI - Structural characterization of the lipid A component of Pseudomonas aeruginosa wild-type and rough mutant lipopolysaccharides. AB - The structure of the lipid A component of lipopolysaccharides isolated from two wild-type strains (Fisher 2 and 7) and one rough mutant (PAC 605) of Pseudomonas aeruginosa was investigated using chemical analysis, methylation analysis, combined gas-liquid chromatography/mass spectrometry, laser-desorption mass spectrometry and NMR spectroscopy. The lipid A backbone was found to consist of a pyranosidic beta 1,6-linked D-glucosamine disaccharide [beta-D-GlcpN-(1----6)-D GlcpN], phosphorylated in positions 4' and 1. Position 6' of the beta-D-GlcpN-(1- --6)-D-GlcpN disaccharide was identified as the attachment site of the core oligosaccharide and the hydroxyl group at C-4 was not substituted. Lipid A of the three P. aeruginosa strains expressed heterogeneity with regard to the degree of acylation: a hexaacyl as well as a pentaacyl component were structurally characterized. The hexaacyl lipid A contains two amide-bound 3-O-acylated (R)-3 hydroxydodecanoic acid groups [12:0(3-OH)] at positions 2 and 2' of the GlcN dissacharide and two ester-bound (R)-3-hydroxydecanoic acid groups [10:0(3-OH)] at positions 3 and 3'. The pentaacyl species, which represents the major lipid A component, lacks one 10:0(3-OH) residue, the hydroxyl group in position 3 of the reducing GlcN residue being free. In both hexa- and pentaacyl lipid A the 3 hydroxyl group of the two amide-linked 12:0(3-OH) residues are acylated by either dodecanoic (12:0) or (S)-2-hydroxydodecanoic acid [12:0(2-OH)], the lipid A species with two 12:0(2-OH) residues, however, being absent. The presence of only five acyl residues in the major lipid A fraction may account for the low endotoxic activity observed with P. aeruginosa lipopolysaccharide. PMID- 1904819 TI - The synthesis of polyphenylalanine on ribosomes to which erythromycin is bound. AB - Erythromycin binds to the large subunit of Escherichia coli ribosomes at a specific site that is very close to the amino acid of aminoacyl-tRNA bound into the peptidyltransferase center, and to the site to which puromycin is bound, the P and A sites, respectively, of the classical two-site model of ribosome function. Both erythromycin and puromycin affect fluorescence from fluorescent derivatives of aminoacyl-tRNAs, while both puromycin and aminoacyl-tRNAs affect fluorescence of fluorescent derivatives of erythromycylamine. The results demonstrate unequivocally that erythromycin, deacylated tRNA, a peptidyl-tRNA analogue and puromycin can be bound simultaneously to the same ribosome. Nascent peptides of more than a few amino acids in length block binding of erythromycin to the ribosomes but, unlike most other peptides, long polyphenylalanine chains can be synthesized on ribosomes to which erythromycin is bound. It is suggested that this refractory synthesis in the presence of erythromycin reflects the atypical physical and structural properties of polyphenylalanine. PMID- 1904820 TI - Extrapancreatic insulin effect of glibenclamide. AB - In eight patients with uncomplicated non insulin dependent diabetes mellitus, serum insulin levels, serum C-peptide levels and blood glucose levels were measured before and after oral administration of glibenclamide 0.1 mg/kg body weight and a test meal, or after a test meal alone. The rise in serum insulin levels persisted longer after glibenclamide. The initial rise in serum insulin was of the same magnitude in both situations, as was the rise in serum C-peptide levels during the entire 5 h study. It is concluded that glibenclamide is able to maintain a more prolonged increase in serum insulin levels by inhibiting the degradation of insulin in the vascular endothelial cells of the liver. The inhibition contributes to the blood glucose lowering effect of glibenclamide. PMID- 1904821 TI - Interaction between enkephalinergic and dopaminergic systems in stressful situations. AB - Mice exhibit a marked suppression of mobility when they are placed in the same cage in which they had previously received an electric shock. This suppression of motility is believed to be a stress-induced response. [D Ala2,Met5]enkephalinamide (DAMEA, 40 and 80 nmol i.c.v.), a derivative resistant to [Met5]enkephalin-degrading enzyme activity, significantly attenuated the conditioned suppression of motility. The attenuation of conditioned suppression of motility induced by DAMEA was antagonized not only by naloxone (0.1 mg/kg s.c.), but also by 6-hydroxydopamine (6-OHDA, 100 micrograms/mouse, i.c.v.) induced lesions of dopaminergic (DAergic) neurons. Pimozide (100 micrograms/kg i.p.) and a low dose of apomorphine (50 micrograms/kg s.c.) also inhibited the effect of DAMEA. In addition, DAMEA reversed the decrease in DA turnover in the striatum in the conditioned suppression group. These results suggest that the attenuation of conditioned suppression of motility induced by activation of the [Met5]enkephalinergic system may be related to the striatal DAergic system. PMID- 1904822 TI - Antinociceptive effect of paracetamol in rats is partly dependent on spinal serotonergic systems. AB - The possible involvement of bulbo-spinal monoaminergic pathways in the antinociceptive effect of paracetamol was investigated in rats. Serotonergic pathways were lesioned with intrathecal 5,6-dihydroxytryptamine (5,6-DHT), and noradrenergic pathways with 6-hydroxydopamine (6-OHDA). Intact and lesioned rats were tested in the formalin test after i.p. paracetamol (400 mg/kg) or vehicle. Behaviour was scored for 1 h after the dorsal injection of 100 microliters of 5% formalin into one hind paw. Behavioural variables were evaluated with a multivariate statistical procedure, as well as an analysis of variance. Paracetamol itself reduced pain-related behaviour and increased normal motor activity. This antinociceptive effect was reduced in rats lesioned with 5,6-DHT. In lesioned rats paracetamol caused a change in nociceptive behaviour from active, focused behaviour towards passive, protective and non-focused behaviour in the early phase of the formalin test. No significant effect of lesioning with 6-OHDA upon the paracetamol effect was found. These results show that activation of spinal serotonergic systems is involved in the antinociceptive effect of paracetamol. The relative importance of this mechanism in the central effect of paracetamol and the mechanisms that cause the activation remain to be determined. PMID- 1904823 TI - Correlation between enhancement of [3H]flunitrazepam binding and suppression of pentylenetetrazol-induced seizures by L-lysine. AB - L-Lysine enhanced the specific [3H]flunitrazepam (FTZ) binding of bovine brain membranes in vitro. Inhibition of specific [3H]FTZ binding to brain membranes in vitro by pentylenetetrazol (PTZ) at concentrations 0.46 mM and below was reversed by increasing L-lysine concentrations in the incubation mixture; further increase of L-lysine concentration enhanced this binding. However, inhibition of [3H]FTZ binding by PTZ higher than 2.3 mM was reversed only partially by L-lysine. L Lysine enhanced specific [35S]t-butylbicyclophosphorothionate (TBPS) binding on mouse brain membranes in a dose-dependent manner (EC approximately 5 microM). This enhancement was inhibited by PTZ dose dependently. Inhibition of [35S]TBPS binding by PTZ was attenuated slightly by L-lysine. L-Lysine enhanced [3H]FTZ binding in intact mice in a dose- or concentration-dependent manner with an ED50 of 6 mmol/kg body weight or EC50 of 3 mumol/g brain tissue, respectively. Similar effect was observed for L-lysine in ex vivo [3H]FTZ binding study when [3H]FTZ was incubated in vitro with an ED50 of 1 mmol/kg mouse or EC50 of 0.7 mumol/g brain. PTZ not only induced seizures, but also inhibited specific [3H]FTZ binding to brain membranes in a dose-dependent manner. L-Lysine, in a dose-dependent manner, suppressed seizures caused by PTZ at 50 or 60 mg/kg, or prolonged the time of seizure onset (seizure latency) caused by higher doses of PTZ (90 or 100 mg/kg). Pretreatment with L-lysine at 1, 5, 10 or 20 mmol/kg not only reversed the inhibition of the specific [3H]FTZ binding caused by PTZ at 50, 90 or 100 mg/kg, but also enhanced this binding above control level.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1904824 TI - Duck hepatitis B virus: a model to assess efficacy of disinfectants against hepadnavirus infectivity. AB - The efficacy of three proprietary glutaraldehyde disinfectants and their component bases was assessed using the duck hepatitis B virus (DHBV) model. Inactivation of infectivity of undiluted serum containing 10(6.8) ID50/ml DHBV was assessed after a mixture with an equal volume of disinfectant had stood at room temperature for 10 min. A dried spill of infectious serum was simulated using sterile filter paper disks, saturated with serum containing DHBV, dried and then exposed to test disinfectant for 10 min. Residual infectivity, and hence the reduction in virus titre, was determined by inoculation of dilutions of the treated samples into 1-day-old ducklings. A greater than 3 log10 reduction in virus titre could be demonstrated for the disinfectants as well as for some of their component bases. Disinfectant activity varied according to the method of viral presentation but a reduction of exposure time from 10 to 2.5 min did not diminish activity. The experimental protocol permits a comparative and quantitative assessment of the efficacy of both established and new disinfectants. PMID- 1904825 TI - Pharyngeal carriage of Neisseria meningitidis and Neisseria lactamica in households with infants within areas with high and low incidences of meningococcal disease. AB - In a household survey in the Faroe Islands, an isolated community with hyperendemic occurrence of meningococcal disease due to serogroup B 15, 1604 persons were examined for pharyngeal carriage of Neisseria meningitidis and N. lactamica. Two areas were chosen having experienced high (HIA), and two having experienced low incidences (LIA) of disease. Living in HIA compared with LIA was associated with higher risk of N. meningitidis B 15 carriage and lower risk of N. lactamica carriage, with odds ratios of 2.7 (95% confidence interval (CI) 1.4 5.1, P = 0.003) and 0.41 (95% CI 0.31-0.53, P less than 0.0001), respectively. In HIA the risk of N. meningitidis carriage was much lower in non-carriers than carriers of N. lactamica, with an odds ratio of 0.19 (95% CI 0.08-0.47, P = 0.0003); in LIA this association (odds ratio 0.51, P = 0.05) was much weaker. Children 0-14 years had substantially higher risk of being carriers of N. meningitidis group B 15 if the mothers were so, with an odds ratio of 11 (95% CI 4-29, P less than 0.0001). PMID- 1904826 TI - Slide-agglutination for rapid serological typing of Treponema hyodysenteriae. AB - A slide agglutination (SA) test was developed to determine the serogroup of isolates of Treponema hyodysenteriae of serogroups A to F. Rabbit antisera which are normally used for serogrouping T. hyodysenteriae in an agarose gel double diffusion precipitation test (AGDP) were not suitable for SA because they agglutinated isolates from more than one serogroup. The agglutination reaction was made serogroup-specific by cross-absorbing the typing sera for serogroups A to F with whole treponemes from the other 5 of these 6 serogroups of T. hyodysenteriae. The absorbed sera were reacted in slide agglutination tests with 33 isolates of T. hyodysenteriae and with four non-T. hyodysenteriae intestinal spirochaetes. None of the non-T. hyodysenteriae isolates agglutinated, but 27 of the 33 isolates of T. hyodysenteriae did. The results for 26 of the 27 agglutination reactions agreed with the serogroup as determined in AGDP. One of the 6 isolates of T. hyodysenteriae which failed to react in slide agglutination was of serogroup B, 1 of serogroup D, 1 each were from new serogroups G, H and I, and 1 was untypable in AGDP. PMID- 1904827 TI - Eosinophilic cellulitis: histologic features in a cutaneous mastocytoma. AB - A cutaneous mastocytoma with associated histologic features of eosinophilic cellulitis is reported. The tumor occurred as a small, asymptomatic lesion on the left thigh of a 4-year-old boy. Microscopically, an accumulation of mast cells, microgranulomas, eosinophils and 'flame figures' was present. A pathogenesis involving mast cell degranulation, eosinophil chemotactic factors and eosinophil major basic protein is discussed. PMID- 1904828 TI - Activation of the prophenoloxidase cascade and initiation of nodule formation in locusts by bacterial lipopolysaccharides. AB - The activation of the prophenoloxidase (proPO) system of the locusts, Schistocerca gregaria and Locusta migratoria, by several bacterial lipopolysaccharides (LPS) is described. Activation of proPO by LPS occurred only in the presence of whole blood homogenates and not with hemocyte lysate preparations alone. Levels of phenoloxidase generated by the different LPSs in vitro were also correlated with numbers of nodules formed in vivo by injection of these LPSs. This further strengthens the evidence for the involvement of proPO activation in the insect cellular defenses. Finally, the wisdom in using anticoagulants in order to stabilize fragile hemocytes in studies on the proPO system is discussed. PMID- 1904829 TI - Chicken growth hormone, triiodothyronine and thyrotropin releasing hormone modulation of the levels of chicken natural cell-mediated cytotoxicity. AB - Newly hatched White Leghorn male chicks received dietary supplements of either Triiodothyronine (T3) or Thyrotropin Releasing Hormone (TRH) until 8 weeks of age. Chicken growth hormone (cGH) (10 micrograms/kg BW) was injected into different chicks twice daily for 1 week starting at 7 weeks of age. Separate groups received both T3 and cGH. Natural cell-mediated cytotoxic (NCMC) activity against different target cells was tested. It was found that cytotoxic activity in cells involved in NCMC against P815 mouse mastocytoma was stimulated by cGH alone or in combination with T3 (1 ppm). These findings indicate that cGH and T3 stimulate NCMC activity; and that the cells responsible for this activity may be Natural Killer (NK) cells. PMID- 1904830 TI - A novel lipopolysaccharide-binding hemagglutinin isolated from hemocytes of the solitary ascidian, Halocynthia roretzi: it can agglutinate bacteria. AB - A hemagglutinin was isolated from hemocytes of the ascidian, Halocynthia roretzi, by a procedure including extraction and ion-exchange chromatography on CM cellulose. The molecular weight of the hemagglutinin was estimated to be 120,000 by gel filtration. It was resistant to acid treatment but sensitive to alkali or heat treatment. The hemagglutinating activity was inhibited by heparin, chondroitin sulfate, and lipopolysaccharide (LPS), but not by mono- and disaccharides such as N-acetyl-galactosamine, galactose, and melibiose. The hemagglutinin showed binding ability to heparin and LPS, as demonstrated by heparin-Sepharose chromatography and centrifugation experiments, respectively. It was also found that the hemagglutinin can bind to various bacteria such as Escherichia coli, Bacillus subtilis, Vibrio anguillarum, Pseudomonas perfectomarinus, Achromobacter aquamarinus, and Alteromonas putrefaciens, and can agglutinate all of them. PMID- 1904831 TI - Differential effects of various Ca2+ antagonists. AB - 1. The effects of various Ca antagonists (nicardipine, nifedipine, verapamil, diltiazem, flunarizine, cinnarizine, lidoflazine and papaverine) were studied in one in vitro (inhibition of CaCl2 induced contractions in isolated rat aorta) and two in vivo tests [survival after BaCl2 in the rat and survival after arachidonic acid (AA) in the mouse]. 2. Test substances behave in different ways, thus suggesting varying mechanisms of action. 3. The three tests used are very simple and quick to perform, but taken together give a good preliminary information which allows classification of the products during the screening phase into four subgroups: dihydropyridines, verapamil, diltiazem and diphenylalkylamines. PMID- 1904832 TI - An analysis of positive inotropic effects of nitroglycerin in the canine hearts. AB - 1. Nitroglycerin caused dose-dependent increases in regional myocardial contractile force (MCF) in open-chest dogs, along with dose-dependent decreases in left ventricular end-diastolic (LVEDP) and arterial pressures and an increase in plasma catecholamines level. 2. The increase in MCF could not be completely prevented by propranolol along with a slight decrease in LVEDP and no increase in heart rate, although a nifedipine-produced increase in MCF without a significant decrease in LVEDP disappeared with propranolol despite the same decrease in arterial pressure. PMID- 1904833 TI - Acidotic effect of gaboon viper (Bitis gabonica) venom in the urethane anaesthetized rat. AB - 1. Intravenous venom (4 mg/kg) caused a non-compensated metabolic acidosis. 2. Bicarbonate concentration, base excess, standard base excess and pH all fell dramatically. 3. A respiratory impairment occurred characterized by pulmonary oedema and a fall in arterial pO2. 4. Acidosis occurred soon after venom when pO2 was still normal, indicating that changes in tissue metabolism contributed to the acidosis independently of reduced oxygen availability. PMID- 1904834 TI - Intralobular distribution and quantitation of cytochrome P-450 enzymes in human liver as a function of age. AB - We have used immunohistochemical, immunoblotting and messenger RNA blotting approaches to study the distribution and quantitation of three cytochrome P-450 enzymes, namely P-450 IA2, P-450 IIC and P-450 IIIA and, for comparison, epoxide hydrolase and NADPH-cytochrome P-450 reductase in human liver. Age-related changes in both the amounts and the intralobular distributions of these enzymes were demonstrated, and the enzymes differ in these regards: In fetal liver, P-450 IA2 and P-450 IIC were very low, when present at all, whereas P-450 IIIA, epoxide hydrolase and the reductase were already abundant and found in all the hepatocytes. During the postnatal period, P-450 IIC dramatically increased and was observed in all hepatocytes, the centrilobular ones being more intensely stained. P-450 IIIA was restricted to centrilobular and midzonal hepatocytes in normal adult liver. P-450 IA2 showed this same intralobular distribution; however, its presence was detected only several weeks or months after birth as judged both by immunohistochemical and immunoblotting techniques. Epoxide hydrolase and NADPH-cytochrome P-450 reductase were easily visualized in all hepatocytes regardless of the age of the donor; in child and adult livers, centrilobular hepatocytes were more intensely stained. Immunoreactive protein contents and corresponding messenger RNA levels correlated well with immunohistochemical observations. No major modification was seen in fibrotic liver, whereas both positive and negative cells were observed in cirrhotic liver nodules for all enzymes studied. PMID- 1904835 TI - Prevalence of dual diagnoses of mental and substance abuse disorders in general hospitals. AB - Data from a 1980 discharge survey of general hospitals were analyzed to determine the prevalence of cases with coexisting diagnoses of mental and substance abuse disorders. Twelve percent of total cases (or 208,000 episodes) had dual diagnoses, a proportion similar to that found in another analysis of 1985 data. Of these cases, 55.5 percent had a primary diagnosis of an alcohol or drug disorder, most commonly alcohol- or drug-induced organic brain syndrome. Thirty four percent of cases with a primary diagnosis of mental disorder had depressive neurosis, 24 percent had psychosis, and 19 percent had personality disorder. An additional 18.9 percent of all cases had two or more mental or substance abuse disorders. Dual-diagnosis cases had a shorter mean hospital stay than cases with mental disorder only. PMID- 1904836 TI - HLA class II nucleotide sequences, 1991. AB - The HLA class II sequences included in this compilation are taken from publications listed in the accompanying paper. Nomenclature for factors of the HLA system, 1990 (Bodmer et al. 1991) and Nomenclature for factors of the HLA system, 1989 (Bodmer et al. 1990). Where discrepancies have arisen between reported sequences the original authors have been contacted where possible, and necessary amendments to published sequences have been incorporated into this alignment. Future sequencing may identify errors in this list and we would welcome any evidence that helps to maintain the accuracy of this compilation. In the sequence alignments identity between residues is indicated by a hyphen (-). Unavailable sequence is indicated by an asterisk (*). Gaps in the sequence are inserted to maintain the alignment between different alleles showing variation in amino acid number. PMID- 1904837 TI - Detection of novel sequence heterogeneity and haplotypic diversity of HLA class II genes. AB - Nucleic acid sequences of the second exons of HLA-DRB1, -DRB3/4/5, -DQB1, and DQA1 genes were determined from 43 homozygous cell lines, representing each of the known class II haplotypes, and from 30 unrelated Caucasian subjects, comprising 60 haplotypes. This systematic sequence analysis was undertaken in order to a) determine the existence of sequence microheterogeneity among cell lines which type as identical by methods other than sequencing; b) determine whether direct sequencing of class II genes will identify the presence of more extensive sequence polymorphism at the population level than that identified with other typing methods; c) accurately determine the molecular composition of the known class II haplotypes; and d) study their evolutionary relatedness by maximum parsimony analysis. The identification of seven previously unidentified haplotypes carrying five new allelic amino acid sequences suggests that sequence microheterogeneity at the population level may be more frequent than previously thought. Maximum parsimony analysis of these haplotypes allowed their evolutionary classification and indicates that the higher mutation rate at DRB1 compared to DQB1 loci in most haplotypic groups is inversed in specific haplotype lineages. Furthermore, the extent and localization of gene conversions and point mutations at class II loci in the evolution of these haplotypes is significantly different at each locus. Identification of additional HLA class II molecular microheterogeneity suggests that direct sequence analysis of class II HLA genes can uncover new allelic sequences in the population and may represent a useful alternative to current typing methodologies to study the effects of sequence allelism in organ transplantation. PMID- 1904838 TI - Polymorphism of the class II gene of rat major histocompatibility complex, RT1: partial sequence comparison of the first domain of the RT1.B beta 1 alleles. PMID- 1904840 TI - Iron limitation and the gamma interferon-mediated antihistoplasma state of murine macrophages. AB - The zoopathogenic fungus Histoplasma capsulatum requires iron for growth. Intracellular growth of the fungus within mouse peritoneal macrophages is inhibited by recombinant murine gamma interferon (IFN-gamma). Such treatment of mouse peritoneal macrophages induces a marked downshift in transferrin receptors. We tested whether the antihistoplasma effect of IFN-gamma-treated macrophages is the result of iron deprivation. Treatment of mouse peritoneal macrophages with the intracellular iron chelator deferoxamine inhibits the intracellular growth of H. capsulatum. Exposure of macrophages to holotransferrin antagonizes the effect of both recombinant murine IFN-gamma and deferoxamine treatments. These results suggest that iron restriction may be one of the bases for the IFN-gamma-induced antihistoplasma effect of mouse macrophages. PMID- 1904839 TI - Enteric infection with an obligate intracellular parasite, Encephalitozoon cuniculi, in an experimental model. AB - Rabbits were intrarectally infected with 3 doses (5 x 10(3), 5 x 10(5), and 5 x 10(7] of an obligate intracellular parasite, Encephalitozoon cuniculi, with or without prior colonic lavages. Although chronic administration of enemas seems to interfere to some degree with the intestinal translocation of the parasite, systemic infection was observed in both manipulated and nonmanipulated animals. The animals responded with antibodies of immunoglobulin A (IgA) and IgG isotypes, reflecting the route of infection. They also produced significant amounts of circulating immune complexes composed of IgA and IgG antibodies and E. cuniculi antigens. Lesions compatible with encephalitozoonosis were seen in the liver, kidney, lung, and brain. In all instances, nonmanipulated animals had more severe lesions than manipulated rabbits given the same dose of parasites. Levels of serum antibodies, circulating immune complexes, and histopathologic changes were associated with the infection dose. The presented data suggest that human microsporidiosis may also be transmitted via the rectal route. It is, therefore, of clinical relevance in view of several reports of microsporidian infections in patients with acquired immunodeficiency. PMID- 1904841 TI - Acquisition of iron by Legionella pneumophila: role of iron reductase. AB - Legionella pneumophila has been shown to survive and multiply in a variety of intracellular environments, including protozoa and human mononuclear phagocytes. However, the mechanism by which this organism acquires iron in the intracellular environment has not been studied. Since L. pneumophila does not produce siderophores, alternative methods of iron acquisition were investigated. Virulent strains of L. pneumophila were able to grow in media containing as little as 3 microM iron, whereas avirulent cells required a minimum of 13 microM iron for growth. Neither virulent nor avirulent cells were able to utilize 55Fe bound to transferrin. When incubated in the presence of 55Fe in the form of ferric chloride, both virulent and avirulent cells accumulated equal amounts of iron. The uptake of iron was energy dependent as indicated by inhibition of 55Fe uptake at 4 degrees C and preincubation of the cells with KCN. Treatment of virulent cells with pronase or trypsin had no effect on iron uptake. In contrast, pronase or trypsin treatment of avirulent cells resulted in increased uptake of iron. Iron reductase activity in both virulent and avirulent cells was demonstrated, with the highest specific activity associated with the periplasmic fraction. Maximum reductase activity of virulent cells occurred with NADH as the reductant. In contrast, avirulent cells showed a twofold increase in enzyme activity when NADPH was used as the reductant. These results suggest that an iron reductase is important in iron acquisition by L. pneumophila. PMID- 1904842 TI - Purification and characterization of an extracellular 29-kilodalton phospholipase C from Listeria monocytogenes. AB - We purified and characterized an extracellular phospholipase produced by Listeria monocytogenes. This enzyme was separated as a homogeneous protein of 29 kDa by chromatography on DEAE-52 cellulose and Bio-Gel P100 columns. It is a zinc dependent phospholipase C (PLC) that is mainly active at pH 6 to 7 and expresses lecithinase activity and a weaker sphingomyelinase activity. The exoenzyme also hydrolyzed phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, and sphingomyelin but not phosphatidylinositol. It was distinct from the 36-kDa phosphatidylinositol PLC produced by L. monocytogenes and from the L. ivanovii sphingomyelinase. The pure protein expressed a weak, calcium-independent hemolytic activity and was not toxic in mice. Western immunoblot analysis using a rabbit immune serum raised against the enzyme showed that all virulent strains of L. monocytogenes tested produced in the culture supernatant a 29-kDa PLC. In contrast, no proteins antigenically related to the 29-kDa PLC were detected in supernatants of L. ivanovii, L. seeligeri, L. innocua, or L. welshimeri. The role in virulence of the 29-kDa PLC specifically produced by L. monocytogenes remains to be established. PMID- 1904843 TI - Variable selection for the classification of postoperative cardiac patients. AB - A set of 13 extensively used hemodynamic, ventilatory and gas analysis variables are measured (on-line or off-line) on 200 patients in an intensive care unit (ICU) during the 6 h immediately following cardiac surgery. Since the existence of two well-separated classes of low- and high-risk patients has been previously shown the divergence criterion is then used to identify those variables which, at three equidistant observation times, possess the greatest separation power. Such variables always include the cardiac index (CI), representative of cardiac performance, and two indices related to respiratory efficiency and metabolic rate, i.e. the carbon dioxide production index (VCO2I) and the arterio-venous oxygen difference (avO2D). The Fisher linear classifier, utilizing these three features, is then tested by using the rotation method. The results show good performance of the linear classifier, which exhibits a probability of correct recognition always greater than 87%, thus suggesting the possibility of obtaining interesting improvements by means of more sophisticated classifiers. PMID- 1904844 TI - Pharmacological modulation of a model of bronchial inflammation after aerosol induced active anaphylactic shock in conscious guinea pigs. AB - Twenty-four hours after an active anaphylactic shock induced by inhalation of antigen in conscious guinea pigs sensitized by a large dose of ovalbumin in complete Freund's adjuvant, a noteworthy bronchial inflammation, characterized by increased numbers of neutrophils, mononuclear cells and eosinophils in the bronchoalveolar lavage fluid, was observed. Some drugs administered after the anaphylactic shock were investigated using this model. Disodium cromoglycate primarily reduced the number of mononuclear cells and eosinophils. Dexamethasone and theophylline decreased the number of eosinophils. Salbutamol and mepyramine increased neutrophils. Indomethacin did not give rise to any significant effect. This test appears to be of use for the investigation of anti-inflammatory compounds in the prophylactic treatment of asthma. PMID- 1904845 TI - The cost effectiveness of strategies to reduce barriers to cataract surgery. The Operations Research Group. AB - The cost and effectiveness of eight approaches to reducing barriers to cataract surgery were evaluated in a rural area of South India during 1987-1989. The approaches were based on four intervention alternatives--aphakic motivator (AM), basic eye health worker (BW), screening van (SV), and mass media (MM). Each intervention was offered at two levels of economic incentive: partial, which provides free surgery and hospital stay, and full, which also provides transport from the recipient's village to the hospital and free food during the hospital stay. Evaluations took place in a probability selection of 90 villages, including ten control villages not subjected to either of the interventions. Only costs unique to patients from the intervention villages were considered: Health education and screening costs were included, surgery costs were not. Percentage reductions in the cataract blind backlog and increases in surgical coverage were used as effectiveness measures. Analyses suggest that the SV and AM interventions, both with full economic incentive, offer the greatest advantage. The AM intervention is the more effective of the two, but also the more costly. PMID- 1904846 TI - [Aortic isthmus stenosis: a comparison of resorbable and non-resorb able sutures]. AB - Absorbing vessel suture material presents the particular advantage of unlimited growth potential of young vessels. This is due to low tissue irritation and only a minimum of foreign-body reaction of the tissue. Retrospectively, we compared 9 patients (5 +/- 3 years of age), who underwent resection of the coarctation and end-to-end reanastomosis, with absorbing simple continuous suture material versus 8 patients (7 +/- 5 years of age; NS) with non-absorbing suture material using a prolong-thread suture technique, who were operated between 1980 and 1986. The growth increase before to 4 years after operation (24 +/- 10% in the "absorbing suture group-A" and 36 +/- 27% in the "non-absorbing suture group-B"; NS) just as the pressure gradient (55 +/- 11 mm Hg in group A, 58 +/- 16 mm Hg in group B (NS) before and 6 +/- 8 mm Hg in group A, 5 +/- 9 mm Hg in group B (NS) 4 years after operation) shows no significant difference. Therefore one may say that absorbing material in simple continuous suture technique presents a good alternative to the non-absorbing material in the prolonged-thread suture technique for correction of aortic isthmus stenosis, whereby analogous growth can be expected. PMID- 1904847 TI - Acridine Orange, a precipitant for sulfated glycosaminoglycans, causes mucopolysaccharidosis in cultured fibroblasts. AB - The purpose of the present investigation was to examine whether or not a di cationic amphiphilic compound that is known (1) to be accumulated in lysosomes and (2) to form insoluble complexes with sulfated glycosaminoglycans (sGAG) in vitro, is able to interfere with the lysosomal degradation of sGAG, thus causing mucopolysaccharidosis (MPS) in cultured cells. Acridine Orange (AO) was chosen for this study since it is known to meet the above requirements. Cultured fibroblasts from rat cornea were exposed to AO (0.7 microM to 30 microM) for 72 h; tilorone served as reference compound. AO (1.75 microM to 10 microM) caused MPS in a concentration-dependent manner, higher concentrations were cytotoxic. MPS was demonstrated by cytochemical staining with cuprolinic blue and by measuring the intracellular accumulation of [35S]-GAG. The sGAG-complexing properties of AO were demonstrated by using it as a fixative for the intralysosomal sGAG accumulated in tilorone-treated cells. The present findings give support to the working hypothesis that the MPS induced by di-cationic amphiphilic drugs is due to the formation of insoluble sGAG-drug complexes, with the result that the sGAG become resistant to lysosomal degradation. PMID- 1904848 TI - [Experimental studies of photodynamic therapy of squamous cell cancers with hematoporphyrin derivative]. AB - The target tissue of photodynamic therapy (PDT) of tumours by haematoporphyrin derivative (HPD) in vivo is controversial. A direct attack on the malignant cell itself, an indirect effect via the vascular system supplying the tumour, or a combination of both factors, have been suggested. We investigated this question in squamous cell carcinoma in experimental animals. Histology showed massive interstitial bleeding in carcinomas induced in the mucosa of the cheek pouch of hamsters or in the skin of mice, indicating a vascular response to PDT. However, it was also possible to induce similar changes in the neighbourhood of newly formed vessels at the margin of an inflammatory reaction induced in the cheek pouch of the hamster in the absence of tumour cells. We implanted cells from human squamous cell carcinomas into athymic nude mice and found that carcinoma cells removed immediately after PDT remained viable, whereas tumour cells left in situ died. Thus, the point of action of PDT and HPD in vivo is not the tumour cell itself, but the vascular stroma of the tumour or its immediate vicinity. PMID- 1904849 TI - Comparison of compensatory pituitary and testicular responses to hemicastration between prepubertal and mature rats. AB - Prepubertal (14 days old) and mature (10 to 12 months old) male rats were hemicastrated and killed at selected intervals during a 12-week period to compare the effect of age on acute and chronic pituitary and testicular responses to hemicastration. Testis weight was increased (P less than 0.05) in hemicastrated (HC) prepubertal rats but not in mature rats compared with intact controls. After surgery, serum follicle-stimulating hormone (FSH) concentrations were elevated (P less than 0.05) by hour 12 and day 2 in prepubertal and mature rats, respectively, and remained elevated over control levels for 4 and 8 weeks, respectively. However, the magnitude of the rise in serum FSH following hemicastration was greater in the prepubertal animals. Pituitary FSH concentrations were increased (P less than 0.05) by day 1 in prepubertal HC rats and remained elevated through week 4. In contrast, pituitary FSH levels were unaffected (P greater than 0.05) by hemicastration in mature rats. Serum concentrations of inhibin-alpha were inversely related to serum FSH concentrations in prepubertal HC rats only. Serum testosterone concentrations were reduced (P less than 0.05) following hemicastration in both age groups but recovered to control levels within 24 hours. Neither serum nor pituitary concentrations of luteinizing hormone (LH) were altered by hemicastration (P greater than 0.05) in either age group. In addition, there were no changes (P greater than 0.05) in the concentrations of testicular LH or FSH receptors following hemicastration throughout the 12-week period. However, both receptor contents were increased (P less than 0.05) in prepubertal HC rats in association with the increase in testis size.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1904850 TI - The successful treatment of Branhamella catarrhalis bronchopulmonary infections in adults with amoxycillin. PMID- 1904851 TI - Inactivation of metronidazole by Enterococcus faecalis. AB - The in-vitro inactivation of metronidazole by different clinical isolates of Enterococcus faecalis was investigated by means of association experiments in which Ent. faecalis strains and Bacteroides fragilis group strains were cultured in the same liquid medium. All of the tested Ent. faecalis strains (20 isolates) were able to protect the B. fragilis group strains against the killing effect of metronidazole at a concentration four or eight times higher than the normal MIC. Different strains of Streptococcus (14), Staphylococcus aureus (10), Staph, epidermidis (10) and Escherichia coli (8) failed to exhibit the same effect. When Ent. faecalis strains were cultured anaerobically for 24 h in the presence of 4 mg metronidazole/l, either alone or together with different B. fragilis group strains, no metronidazole could be detected subsequently in the culture supernatants by HPLC. Concomitantly an increase of four or five logs in the viable counts of the co-cultured Bacteroides strains was observed compared with Bacteroides strains cultured alone. Sonicated cell extracts of Ent. faecalis cultured either aerobically or anaerobically were found to inactivate metronidazole to the same extent, whereas the culture supernatants had no such effect. PMID- 1904852 TI - Determination of nabam fungicide in crops by liquid chromatography with postcolumn reaction detection. AB - The ethylenebisdithiocarbamate (EBDC) fungicide, nabam, was determined in several crop matrixes using liquid chromatography with postcolumn reaction detection. After separation by micellar liquid chromatography, nabam (EBDC sodium salt) was acid hydrolyzed to ethylenediamine and fluorigenically labeled with o phthalaldehyde-mercaptoethanol (OPA-MERC). Standard curves were linear from the detection limit of ca 1 ng to 1000 ng. Nabam was recovered in high yield (89 plus or minus 7.7%) over a range of concentrations (0.1 to 20 ppm) from fortified samples of papaya, lettuce, cucumber, spinach, and applesauce using a simple extraction method. Efforts to convert the more popular EBDC fungicides, maneb and mancozeb, to nabam are discussed. PMID- 1904853 TI - Development of a rapid equine serological test (REST) by modified agar-gel immunodiffusion. AB - A rapid equine serological test (REST) has been developed for detection of horse meat in a wide variety of raw meat products. The test is an adaptation of previously developed field screening immunodiffusion tests for beef, poultry, pork, and sheep detection. Results show that the REST test was specific, sensitive, and accurate in the analysis of 101 samples. PMID- 1904854 TI - Leakage of periplasmic enzymes from envA1 strains of Escherichia coli. AB - Previous work ascribed antibiotic hypersensitivity of the envA1 mutant to lowered lipopolysaccharide levels and exposure of the lipid bilayer. In the detailed characterization of the EnvA permeability phenotype presented here, the envA1 mutation was shown to confer leakage of the periplasmic enzymes beta-lactamase and RNase I. Leakage was observed in three different genetic backgrounds, including the original envA1 strain and its parent. In contrast, no detectable leakage of the cytoplasmic enzyme beta-galactosidase was observed. Sensitivity of envA1 strains to a range of antibiotics not previously reported was tested, and lipophilicity (partition coefficient) of a number of antibiotics was determined. On the basis of observations of periplasmic leakage and sensitivity to large hydrophilic antibiotics and lysozyme, part of the permeability phenotype of the envA1 mutant is proposed to be due to transient rupture and resealing of the EDTA sensitive outer membrane layer. In this regard, the EnvA permeability phenotype falls into a general class of permeability/leaky mutants of both Escherichia coli and Salmonella typhimurium. PMID- 1904855 TI - Cloning and characterization of the Salmonella typhimurium ada gene, which encodes O6-methylguanine-DNA methyltransferase. AB - The ada gene of Escherichia coli encodes O6-methylguanine-DNA methyltransferase, which serves as a positive regulator of the adaptive response to alkylating agents and as a DNA repair enzyme. The gene which can make an ada-deficient strain of E. coli resistant to the cell-killing and mutagenic effects of N-methyl N'-nitro-N-nitrosoguanidine (MNNG) has been cloned from Salmonella typhimurium TA1538. DNA sequence analysis indicated that the gene potentially encoded a protein with a calculated molecular weight of 39,217. Since the nucleotide sequence of the cloned gene shows 70% similarity to the ada gene of E. coli and there is an ada box-like sequence (5'-GAATTAAAACGCA-3') in the promoter region, we tentatively refer to this cloned DNA as the adaST gene. The gene encodes Cys 68 and Cys-320, which are potential acceptor sites for the methyl group from the damaged DNA. The multicopy plasmid carrying the adaST gene significantly reduced the frequency of mutation induced by MNNG both in E. coli and in S. typhimurium. The AdaST protein encoded by the plasmid increased expression of the ada'-lacZ chromosome fusion about 5-fold when an E. coli strain carrying both the fusion operon and the plasmid was exposed to a low concentration of MNNG, whereas the E. coli Ada protein encoded by a low-copy-number plasmid increased it about 40-fold under the same conditions. The low ability of AdaST to function as a positive regulator could account for the apparent lack of an adaptive response to alkylation damage in S. typhimurium. PMID- 1904856 TI - Mannitol-specific phosphoenolpyruvate-dependent phosphotransferase system of Enterococcus faecalis: molecular cloning and nucleotide sequences of the enzyme IIIMtl gene and the mannitol-1-phosphate dehydrogenase gene, expression in Escherichia coli, and comparison of the gene products with similar enzymes. AB - Enzyme IIIMtl is part of the mannitol phosphotransferase system of Enterococcus faecalis. It is phosphorylated in a reaction sequence requiring enzyme I and heat stable phosphocarrier protein (HPr). The phospho group is transferred from enzyme IIIMtl to enzyme IIMtl, which then catalyzes the uptake and concomitant phosphorylation of mannitol. The internalized mannitol-1-phosphate is oxidized to fructose-6-phosphate by mannitol-1-phosphate dehydrogenase. In this report we describe the cloning of the mtlF and mtlD genes, encoding enzyme IIIMtl and mannitol-1-phosphate dehydrogenase of E. faecalis, by a complementation system designed for cloning of gram-positive phosphotransferase system genes. The complete nucleotide sequences of mtlF, mtlD, and flanking regions were determined. From the gene sequences, the primary translation products are deduced to consist of 145 amino acids (enzyme IIIMtl) and 374 amino acids (mannitol-1 phosphate dehydrogenase). Amino acid sequence comparison confirmed a 41% similarity of E. faecalis enzyme IIIMtl to the hydrophilic enzyme IIIMtl-like portion of enzyme IIMtl of Escherichia coli and 45% similarity to enzyme IIIMtl of Staphylococcus carnosus. The putative N-terminal NAD+ binding domain of mannitol-1-phosphate dehydrogenase of E. faecalis shows a high degree of similarity with the N terminus of E. coli mannitol-1-phosphate dehydrogenase (T. Davis, M. Yamada, M. Elgort, and M. H. Saier, Jr., Mol. Microbiol. 2:405-412, 1988) and the N-terminal part of the translation product of S. carnosus mtlD, which was also determined in this study. There is 40% similarity between the dehydrogenases of E. faecalis and E. coli over the whole length of the enzymes. The organization of mannitol-specific genes in E. faecalis seems to be similar to the organization in S. carnosus. The open reading frame for enzyme IIIMtl E. faecalis is followed by a stem-loop structure, analogous to a typical Rho independent terminator. We conclude that the mannitol-specific genes are organized in an operon and that the gene order is mtlA orfX mtlF mtlD. PMID- 1904857 TI - Up-promoter mutations in the trpBA operon of Pseudomonas aeruginosa. AB - In Pseudomonas aeruginosa, the operon encoding tryptophan synthase (trpBA) is positively regulated by the TrpI protein and an intermediate in tryptophan biosynthesis, indoleglycerol phosphate (InGP). A gene fusion in which the trpBA promoter directs expression of the Pseudomonas putida xylE gene was constructed. By using a P. putida F1 todE mutant carrying this fusion on a plasmid, three cis acting mutations that increased xylE expression enough to allow the todE strain to grow on toluene were isolated. The level of xylE transcript from the trpBA promoter was increased in all three mutants. All three mutations are base substitutions located in the -10 region of the trpBA promoter; two of these mutations make the promoter sequence more like the Escherichia coli RNA polymerase sigma 70 promoter consensus sequence. The activities of the wild-type and mutant trpBA promoters, as monitored by xylE expression, were assayed in P. putida PpG1 and in E. coli. The up-regulatory phenotypes of the mutants were maintained in the heterologous backgrounds, as was trpI and InGP dependence. These results indicate that the P. aeruginosa trpBA promoter has the key characteristics of a typical E. coli positively regulated promoter. The results also show that the P. aeruginosa and P. putida trpI activator gene products are functionally interchangeable. PMID- 1904858 TI - Activation of the trpBA promoter of Pseudomonas aeruginosa by TrpI protein in vitro. AB - We have developed an in vitro transcription system in which purified TrpI protein and indoleglycerol phosphate (InGP) activate transcription initiation at the trpBA promoter (trpPB) and repress initiation at the trpI promoter (trpPI) of Pseudomonas aeruginosa. The phenotypes resulting from mutations in the -10 region of both promoters indicate that the -10 region consensus sequence in P. aeruginosa is probably the same as that in Escherichia coli. Furthermore, in the absence of TrpI and InGP, the activities of the two promoters are inversely correlated: down mutations in trpPI lead to increased activity of trpPB, and up mutations in trpPB cause a decrease in trpPI activity. These results are a consequence of the fact that the two promoters overlap, so that RNA polymerase cannot form open complexes with both promoters simultaneously. Thus, in theory, by preventing RNA polymerase from binding at trpPI, TrpI protein could indirectly activate trpPB. However, oligonucleotide-induced mutations that completely inactivate trpPI do not relieve the requirement for TrpI and InGP to activate trpPB. Therefore, activation of trpPB is mediated by a direct effect of TrpI on transcription initiation at trpPB. In addition, the oligonucleotide-induced mutations in trpPI alter site II, the weaker of two TrpI binding sites identified in DNase I and hydroxyl radical footprinting studies (M. Chang and I. P. Crawford, Nucleic Acids Res. 18:979-988, 1990). Since these mutations prevent full activation of trpPB, we conclude that specific base pairs in site II are required for activation. PMID- 1904859 TI - Molecular cloning and characterization of two genes encoding sigma factors that direct transcription from a Bacillus thuringiensis crystal protein gene promoter. AB - Two sigma factors, sigma 35 and sigma 28, direct transcription from the Bt I and Bt II promoters of the cryIA(a) gene of Bacillus thuringiensis; this gene encodes a lepidopteran-specific crystal protoxin. These sigma factors were biochemically characterized in previous work (K. L. Brown and H. R. Whiteley, Proc. Natl. Acad. Sci. USA 85:4166-4170, 1988; K. L. Brown and H. R. Whiteley, J. Bacteriol. 172:6682-6688, 1990). In this paper, we describe the cloning of the genes encoding these two sigma factors, as well as their nucleotide and deduced amino acid sequences. The deduced amino acid sequences of the sigma 35 and sigma 28 genes show 88 and 85% identity, respectively, to the sporulation-specific sigma E and sigma K polypeptides of Bacillus subtilis. Transformation of the sigma 35 and sigma 28 genes into B. subtilis shows that the respective B. thuringiensis sigma factor genes can complement spoIIG55 (sigma E) and spoIIIC94 (sigma K) defects. Further, B. thuringiensis core polymerase reconstituted with either the sigma 35 or sigma 28 polypeptide directs transcription from B. subtilis promoters recognized by B. subtilis RNA polymerase containing sigma E and sigma K, respectively. Thus, sigma 35 and sigma 28 of B. thuringiensis appear to be functionally equivalent to sigma E and sigma K of B. subtilis. However, unlike the situation for sigma K in B. subtilis, the homologous sigma 28 gene in B. thuringiensis does not result from a late-sporulation-phase chromosomal rearrangement of two separate, partial genes. PMID- 1904860 TI - Lactococcin A, a new bacteriocin from Lactococcus lactis subsp. cremoris: isolation and characterization of the protein and its gene. AB - A new bacteriocin, termed lactococcin A (LCN-A), from Lactococcus lactis subsp. cremoris LMG 2130 was purified and sequenced. The polypeptide contained no unusual amino acids and showed no significant sequence similarity to other known proteins. Only lactococci were killed by the bacteriocin. Of more than 120 L. lactis strains tested, only 1 was found resistant to LCN-A. The most sensitive strain tested, L. lactis subsp. cremoris NCDO 1198, was inhibited by 7 pM LCN-A. By use of a synthetic DNA probe, lcnA was found to be located on a 55-kb plasmid. The lcnA gene was cloned and sequenced. The sequence data revealed that LCN-A is ribosomally synthesized as a 75-amino-acid precursor including a 21-amino-acid N terminal extension. An open reading frame encoding a 98-amino-acid polypeptide was found downstream of and in the same operon as lcnA. We propose that this open reading frame encodes an immunity function for LCN-A. In Escherichia coli lcnA did not cause an LCN-A+ phenotype. L. lactis subsp. lactis IL 1403 produced small amounts of the bacteriocin and became resistant to LCN-A after transformation with a recombinant plasmid carrying lcnA. The other lactococcal strains transformed with the same recombinant plasmid became resistant to LCN-A but did not produce any detectable amount of the bacteriocin. PMID- 1904862 TI - Therapeutic drug monitoring for antidepressants: efficacy, safety, and cost effectiveness. AB - Therapeutic drug monitoring (TDM) of tricyclic antidepressants (TCAs) is a cost effective tool to increase efficacy and safety in patients suffering from major depressive illness. The concentration:antidepressant response relationships of nortriptyline, desipramine, and amitriptyline conform to a curvilinear relationship between concentration:antidepressant response; whereas, imipramine conforms to a linear relationship. Besides improving efficacy, TDM identifies the subset of patients who are at risk to develop excessive plasma TCA levels with potential resultant central nervous system and cardiovascular toxicity. Taking both the efficacy and safety data into account, cost:benefit analyses demonstrate that TDM is cost effective when used once as a standard aspect of care in the TCA treatment of patients with major depressive illness. PMID- 1904861 TI - Species-specific uptake of DNA by gonococci is mediated by a 10-base-pair sequence. AB - Piliated Neisseria gonorrhoeae are known to be transformed less readily if transforming DNA competes with DNA containing the 10-bp sequence GCCGTCTGAA. It has been postulated that the 10-bp sequence is a recognition sequence which is required for efficient DNA uptake. We show that the presence of various forms of this 10-bp sequence results in increased uptake of double-stranded DNA into a DNase-resistant state and allows genetic transformation by an otherwise nontransformable plasmid. PMID- 1904863 TI - Anoxia induces human immunodeficiency virus expression in infected T cell lines. AB - The effects of oxygen deprivation, or anoxia, on human immunodeficiency virus (HIV-1) expression in chronically (ACH.2) and acutely (H9/HIV-1-IIIB) infected cell lines was investigated. Temporary cellular anoxia has previously been shown to activate transcription of endogenous type C leukemia virus sequences, resulting in a significant increase in retroviral RNA within the cell (1). Here we report a 15-fold increase in HIV-1-specific RNA in unstimulated ACH.2 T cells within 24 h of anoxia. This induction of RNA is accompanied by an accumulation of intracellular p24 gag protein as well as an increase in envelope protein. Anoxia induces a further increase in total HIV-1 RNA in ACH.2 cells prestimulated to produce virus by phorbol 12-myristate 13-acetate and in H9 T cells acutely infected with HIV-1-IIIB. The induction of RNA in ACH.2 cells appears to be reversible. Anoxic culture for 24 h followed by a 24-h re-oxygenation period results in a return to "resting state" levels of HIV-1 RNA. These data indicate that oxygen tension within the cellular environment modulates HIV-1 expression, providing a model system in which to study the reversible regulation of HIV-1 RNA and viral gene products within the cell. PMID- 1904864 TI - Structures of mucin-type sugar chains of the galactosyltransferase purified from human milk. Occurrence of the ABO and Lewis blood group determinants. AB - The mucin-type sugar chains of human milk galactosyltransferase samples purified from two donors with different blood types were released by alkaline borohydride treatment and quantitatively labeled by N-[3H]acetylation. The radioactive oligosaccharides thus obtained were fractionated by high performance liquid chromatography and immobilized lectin chromatography, and their structures were studied by sequential digestion with endo- or exoglycosidases, methylation analysis, and periodate oxidation. It was revealed that the structures of the mucin-type sugar chains of galactosyltransferase are extremely various, and many blood group determinants are expressed on more than 13 different backbone sugar chains. The characteristic features of the sugar chains could be summarized as follows. 1) The sugar chains of both samples are composed of core 1, Gal beta 1-- -3GalNAc, and core 2, GlcNAc beta 1----6(Gal beta 1----3)GalNAc. 2) One or two N acetyllactosamine repeating units extend from the core through GlcNAc beta 1--- 6Gal and GlcNAc beta 1----3 Gal linkages. 3) Blood group determinants are expressed in accord with the blood types of the donors: sample 1 from a donor of blood type O, Lea+b- contains oligosaccharides with Lea and X determinants, and sample 2 from a donor of B, Lea-b- contains those with H, X, Y, and B determinants. PMID- 1904865 TI - Active site-directed inhibition by optically pure epoxyalkyl cellobiosides reveals differences in active site geometry of two 1,3-1,4-beta-D-glucan 4 glucanohydrolases. The importance of epoxide stereochemistry for enzyme inactivation. AB - 1,3-1,4-beta-D-Glucan 4-glucanohydrolases (EC 3.2.-1.73) from Bacillus subtilis and barley (Hordeum vulgare) with identical substrate specificities but unrelated primary structures have been probed with (R,S)-epoxyalkyl (-propyl, -butyl, pentyl) beta-cellobiosides and with optically pure (3S)- and (3R)-3,4 cellobiosides as active site-directed inhibitors. The optimal aglycon length for inactivation differs for the two enzymes, and they are differentially inhibited by the pure epoxybutyl beta-cellobioside diastereoisomers. The (3S)-epoxybutyl beta-cellobioside inactivates the B. subtilis enzyme much more efficiently than does the (3R)-isomer, whereas the reverse is true for the barley enzyme. Both enzymes are inactivated by a mixture of the stereoisomers at a rate intermediate of that observed with the individual isomers. The two beta-glucan endohydrolases may therefore employ sterically different mechanisms to achieve glycoside bond hydrolysis in their common substrate. The efficiency and specificity of epoxide based "suicide" inhibitors may be enhanced significantly by the use of inhibitors bearing only one stereoisomeric form of the epoxide group. PMID- 1904866 TI - Mechanism of formation of the Maillard protein cross-link pentosidine. Glucose, fructose, and ascorbate as pentosidine precursors. AB - Pentosidine is a recently discovered fluorescent protein cross-link from human extracellular matrix that involves lysyl and arginyl residues in an imidazo (4, 5b) pyridinium ring. Pentosidine could be synthesized in vitro by the reaction of ribose, lysine, and arginine. The potential biological significance of the molecule prompted us to investigate its mechanism of formation from D-ribose and key Maillard intermediates, as well as from other potential precursor sugars. The yield of pentosidine from N alpha-t-Boc-lysine, N alpha-t-Boc-arginine, and D ribose was highest at pH 9.0 and 65 degrees C, but was unaffected by reactant ratios at alkaline pH suggesting an important role for base catalysis. Ribated Boc-lysine on incubation with N alpha-t-Boc-arginine afforded a fluorescent compound with UV, fluorescence, 1H NMR, and MS properties identical with those from native or synthetic pentosidine. 3-Deoxypentosone, however, was not a major pentosidine precursor. Pentosidine became slowly detectable in bovine serum albumin incubated with 0.25 M and 1.0 M glucose and reached, at 30 days, 13.2 and 17 pmol/mg bovine serum albumin, respectively. Spectroscopical properties of glucose-derived pentosidine were identical with those from ribose-derived pentosidine. Pentosidine formed from glucated Boc-lysine with N alpha-t-Boc arginine in higher yields than from glucose under standard conditions. Fructose, and unexpectedly ascorbate, also formed pentosidine in similar yields as glucose. The discovery that pentosidine can form not only from pentoses but also from hexoses and ascorbate raises major new questions concerning biochemical pathways of the Maillard reaction in vivo. PMID- 1904867 TI - Formation of pentosidine during nonenzymatic browning of proteins by glucose. Identification of glucose and other carbohydrates as possible precursors of pentosidine in vivo. AB - A fluorescent compound has been detected in proteins browned during Maillard reactions with glucose in vitro and shown to be identical to pentosidine, a pentose-derived fluorescent cross-link formed between arginine and lysine residues in collagen (Sell, D. R., and Monnier, V. M. (1989) J. Biol. Chem. 264, 21597-21602). Pentosidine was the major fluorophore formed during nonenzymatic browning of ribonuclease and lysozyme by glucose, but accounted for less than 1% of non-disulfide cross-links in protein dimers formed during the reaction. Pentosidine was formed in greatest yields in reactions of pentoses with lysine and arginine in model systems but was also formed from glucose, fructose, ascorbate, Amadori compounds, 3-deoxyglucosone, and other sugars. Pentosidine was not formed from peroxidized polyunsaturated fatty acids or malondialdehyde. Its formation from carbohydrates was inhibited under nitrogen or anaerobic conditions and by aminoguanidine, an inhibitor of advanced glycation and browning reactions. Pentosidine was detected in human lens proteins, where its concentration increased gradually with age, but it did not exceed trace concentrations (less than or equal to 5 mumol/mol lysine), even in the 80-year-old lens. Although its precise carbohydrate source in vivo is uncertain and it is present in only trace concentrations in tissue proteins, pentosidine appears to be a useful biomarker for assessing cumulative damage to proteins by nonenzymatic browning reactions with carbohydrates. PMID- 1904868 TI - Promoter elements and factors required for hepatic transcription of the human ApoA-II gene. AB - The apolipoprotein A-II (apoA-II) gene regulatory region -911 to +29 strongly promotes the transcription of the promotorless chloramphenicol acetyltransferase (CAT) gene in cells of hepatic (HepG2) and intestinal (CaCo2) origin but not in HeLa cells. Deletion of nucleotides -911 to -860 decreased the hepatic and intestinal transcription to 7% and 18% of control, respectively. Further progressive deletions extending to nucleotides -614, -440, -230, and -80 abolished both hepatic and intestinal transcription, indicating that the distal promoter region -911 to -614 contains regulatory elements that are essential for intestinal and hepatic transcription. An internal deletion of the -614 to -230 region decreased hepatic transcription 60% while it increased intestinal transcription 140% of control indicating that the elements which control hepatic and intestinal transcription of the apoA-II gene may be different within this regulatory region. DNase I footprinting analysis with rat liver nuclear extracts identified 14 protected regions: A, -40 to -33; B, -65 to -42; C, -126 to -110; D, -276 to -255; E, -377 to -364; F, -404 to -384; G, -468 to -455; H, -573 to 554; I, -706 to -680; J, -734 to -716; K, -760 to -743; L, -803 to -773; M, -853 to -829, and N, -903 to -879, as the DNA binding sites for nuclear factors. Five of the regions (B, C, G, H, and K) bind to heat-stable factors. DNA binding gel electrophoretic assays indicated that region N (-903 to -879), which is essential for efficient transcription, binds predominantly a nuclear activity designated AIIN3. This activity is present in cells of hepatic and intestinal origin but absent in HeLa cells. Similar analysis showed that region H (-573 to -554) binds to the liver-specific factor HNF1/LFB1. Deletion of this region decreased hepatic and intestinal transcription 80 and 64% of control, respectively, suggesting that HNF1/LFB1 or a related activity contributes to optimal transcription but is not essential for the tissue-specific expression of the human apoA-II gene. PMID- 1904869 TI - Mutations that affect the folding of ribose-binding protein selected as suppressors of a defect in export in Escherichia coli. AB - It has been proposed (Randall, L. L., and Hardy, S. J. S. (1986) Cell 46, 921 928) that export of protein involves a kinetic partitioning between the pathway that leads to productive export and the pathway that leads to the folding of polypeptides into a stable conformation that is incompatible with export. As predicted from this model, a decrease in the rate of export of maltose-binding protein to the periplasmic space in Escherichia coli resulting from a defect in the leader sequence was able to be partially overcome by a mutation that slowed the folding of the precursor, thereby increasing the time in which the polypeptide was competent for export. (Liu, G., Topping, T. B., Cover, W. H., and Randall, L. L. (1988) J. Biol. Chem. 263, 14790-14793). Here we describe mutations of the gene encoding ribose-binding protein that were selected as suppressors of a defect in export of that protein and that alter the folding pathway. We propose that selection of such suppressors may provide a general method to obtain mutations that affect the folding properties of any protein that can be expressed and exported in E. coli. PMID- 1904870 TI - The importance of a distal hydrogen bonding group in stabilizing the transition state in subtilisin BPN'. AB - Stabilization of an oxyanion transition state is important to catalysis of peptide bond hydrolysis in all proteases. For subtilisin BPN', a bacterial serine protease, structural data suggest that two hydrogen bonds stabilize the tetrahedral-like oxyanion intermediate: one from the main chain NH of Ser221 and another from the side chain NH2 of Asn155. Molecular dynamic studies (Rao, S., N., Singh, U., C. Bush, P. A., and Kollman, P. A. (1987) Nature 328, 551-554) have indicated the gamma-hydroxyl of Thr220 may be a third hydrogen bond donor even though it is 4A away in the static x-ray structure. We have probed the role of Thr220 by replacing it with serine, cysteine, valine, or alanine by site directed mutagenesis. These substitutions were intended to alter the size and hydrogen bonding ability of residue 220. Removal of the gamma-hydroxyl group reduced the transition state stabilization energy (delta delta GT) by 1.8-2.1 kcal/mol depending upon the substitution. By comparison, removal of the gamma methyl group in the Thr220 to serine mutation only decreased delta GT by 0.5 kcal/mol. The gamma-hydroxyl of Thr220 is most important for catalysis, not substrate binding, because virtually all of the effects were on kcat and not KM. The role of the Thr220 hydroxyl is functionally independent from the amide NH2 of Asn155 because the free energy effects of double alanine mutants at these two positions are additive. These data indicate that a distal hydrogen bond donor, namely the hydroxyl of Thr220, plays a functionally important role in stabilizing the oxyanion transition state in subtilisin which is independent of Asn155. PMID- 1904871 TI - Free energy perturbation calculations on binding and catalysis after mutating threonine 220 in subtilisin. AB - We present the results of free energy perturbation calculations on binding and catalysis of a tetrapeptide substrate, acetyl-Phe-Ala-Ala-Phe-NMe, by native subtilisin BPN' and a subtilisin BPN' mutant (Thr220----Ala220). The calculated difference in the free energy of binding was 0.70 +/- 0.72 kcal/mol. The calculated difference in the free energy of catalysis was 1.48 +/- 0.89 kcal/mol. These calculated values compare well with the experimental values in which another substrate, succinyl-Ala-Ala-Pro-Phe-p-nitroanilide, was used. These findings suggest that Thr220 is more important for catalysis than substrate binding. PMID- 1904872 TI - Isolation and characterization of bovine haptoglobin from acute phase sera. AB - A macromolecular hemoglobin-binding protein, which was not detectable in normal bovine sera but appeared during acute phase inflammation, was purified, characterized, and designated as bovine haptoglobin (Hp). The purified protein had a molecular mass of 1,000-2,000 kDa, and was composed of two kinds of peptides, a 20-kDa peptide (alpha chain) and a 35-kDa glycopeptide (beta chain) linked by disulfide bonds. Amino acid composition and N-terminal sequence analyses revealed that both peptides were homologous to each counterpart of human Hp. Studies using some reducing reagents proved that highly polymerized Hp in serum was composed of 2-20 polymerized forms of alpha 2 beta 2 tetramer. Hp could bind one molecule of hemoglobin/alpha 2 beta 2 unit. Hp with smaller sizes obtained from native Hp by partial reduction with cysteine showed almost the same Hb-binding capacity. PMID- 1904873 TI - Characterization of recombinant Bacillus megaterium cytochrome P-450 BM-3 and its two functional domains. AB - Bacillus megaterium cytochrome P-450BM-3 and its two functional domains, the heme and flavin domains, have been purified and characterized using an Escherichia coli expression system. Recombinant P-450BM-3 behaves both spectrally and enzymatically the same as the enzyme produced from the natural host, B. megaterium, and another E. coli system recently described (Bouddupalli, S. S., Estabrook, R. W., and Peterson, J. A. (1990) J. Biol. Chem. 265, 4233-4239). Reduction of the flavins in P-450BM-3 domain with NADPH appears to be very similar to microsomal P-450 reductases where two reducing equivalents are consumed to fully reduce the FMN while the FAD is converted to the semiquinone in an one electron reduction. NADPH reduction of the heme occurs only in the presence of substrate suggesting, by analogy with the cytochrome P-450CAM system, a possible increase in iron redox potential of the heme upon substrate binding which facilitates electron transfer from the flavins to the heme. The flavin domain retains a high level of cytochrome c reductase activity and also reacts with NADPH to give a 3-electron reduced product. The heme domain retains the ability to bind substrate and generates the characteristic 450-nm absorption band upon reduction in the presence of CO. The heme domain has been crystallized and a preliminary set of x-ray diffraction data obtained. PMID- 1904874 TI - Characterization of the mutation responsible for aspartylglucosaminuria in three Finnish patients. Amino acid substitution Cys163----Ser abolishes the activity of lysosomal glycosylasparaginase and its conversion into subunits. AB - The mutation that causes a deficiency of the lysosomal amidase, glycosylasparaginase, has been characterized in fibroblasts from three Finnish patients diagnosed with aspartylglucosaminuria (AGU). The polymerase chain reaction was used to amplify the glycosylasparaginase protein coding sequence from the three AGU patients in order to compare them to the normal sequence from a full-length human placenta cDNA clone HPAsn.6 (Fisher, K.J., Tollersrud, O.K., and Aronson, N.N., Jr. (1990) FEBS Lett. 269, 440-444). Two base changes were found to be common to all three Finnish AGU patients, a G482----A transition that results in an Arg161----Gln substitution and a G488----C transversion that causes Cys163----Ser. Detection of both point mutations from PCR-amplified cDNA or genomic DNA was facilitated by their creation of new endonuclease restriction sites. Expression studies in COS-1 cells revealed only the Cys163----Ser mutation caused a deficiency of glycosylasparaginase activity. This same substitution also prevented the normal posttranslational processing of the precursor glycosylasparaginase polypeptide into its alpha and beta subunits. Cell-free expression of the single-chain glycosylasparaginase precusor did not produce an active enzyme, suggesting that post-translational generation of subunits may be required for catalytic activity. PMID- 1904875 TI - An approach to the optimization of preparation of bioprosthetic heart valves. AB - The stress and strain states of the valve leaflets during fixation with glutaraldehyde affect their final mechanical parameters. Comparative studies of the stress-strain relationships of aortic valve leaflet strips from fresh, statically and dynamically fixed porcine and human valves were made. Static pressures of 5 mmHg, 16 mmHg, and 95 mmHg result in stress-strain relationships which are in a region between that of fresh porcine and fresh human leaflet strips in the circumferential direction, while they are far from that of fresh porcine tissue (larger strains) in the radial direction. Leaflet strips, fixed under dynamic loading between zero and a predefined maximum load, set at an early post-transition state, give parameters not significantly different from those of human valves. PMID- 1904876 TI - Evaluation of a synthetic wound dressing capable of releasing silver sulfadiazine. AB - A silver sulfadiazine-impregnated poly-L-leucine wound dressing, AgSD-medicated wound dressing, was evaluated for antibacterial capacity against Pseudomonas aeruginosa and cytotoxicity to human fibroblasts and human epidermal keratinocytes. This wound dressing contained 0.4 mg AgSD/cm2. Antibacterial capacity was examined on experimentally infected wound surfaces (3.4 x 10(4) P. aeruginosa organisms/gm) on the dorsum of mice. The AgSD-medicated wound dressing showed effective bacterial control. Cytotoxicity was examined on a monolayer of cells formed in culture dishes. Cellular damage was reduced by the controlled release of AgSD from the hydrophobic poly-L-leucine sponge matrix of the AgSD medicated wound dressing. Cytotoxicity of the AgSD-medicated wound dressing was much lower than that of 1% AgSD cream. PMID- 1904878 TI - Nutrient substrates. Making choices in the 1990s. PMID- 1904877 TI - Bacterial virulence and host selection: bacteria "select" patients to infect. AB - A clinically lethal strain of Pseudomonas aeruginosa was tested and its growth patterns in normal plasma and in normal whole blood clotted with thrombin were compared. Two stock cultures were used; one was maintained in liquid nitrogen and one was passed from plate to plate 24 times on blood agar plates at room temperature. The results showed that plasma alone and whole blood controlled the growth of a clinically pathogenic strain of P. aeruginosa consistently and uniquely for each donor, dependent on size of inoculum, length of incubation, and means by which the culture was maintained. The changing virulence of an organism and its unique growth patterns in different individuals' plasma and whole blood may explain why patients exposed to the same organisms within the same environment vary in susceptibility to clinical infection. PMID- 1904879 TI - Measurement of cerebral monoamine oxidase B activity using L-[11C]deprenyl and dynamic positron emission tomography. AB - A tracer kinetic procedure was developed for the measurement of monoamine oxidase type B (MAO-B) activity using L-[11C]deprenyl and positron emission tomography (PET). The kinetic model consisted of two tissue compartments with irreversible binding to the second compartment (three rate constants). In addition, a blood volume component was included. Special attention was given to the accurate measurement of the plasma and whole blood input functions. The method was applied to the measurement of the dose-response curve of a reversible MAO-B inhibitor (Ro 19-6327). From the results, it followed that the rate constant for irreversible binding (k3) appeared to be a better index of MAO-B activity than the net influx constant Ki. Furthermore, regional analysis demonstrated that Ki, but not k3, was flow dependent. This implies that full kinetic analysis is required for an accurate assessment of MAO-B activity. PMID- 1904880 TI - Extracellular pH in the brain during ischemia: relationship to the severity of lactic acidosis. AB - On the basis of data showing a bimodal distribution of values for extracellular pH (pHe), and a discontinuous delta PCO2/delta lactate relationship, Kraig et al. (1986) proposed that H+ is grossly compartmentalized between neurons and glia in the ischemic brain. We measured delta pHe during ischemia, varying ischemic lactate contents between 9 and 38 mmol kg-1. No bimodal distribution was found, but delta pHe varied linearly with lactate content. Because we have also failed to record a discontinuous delta PCO2/delta lactate relationship, we conclude that major compartmentation of H+ does not occur during ischemia. PMID- 1904882 TI - Integrating cost and quality. PMID- 1904881 TI - Large-scale isolation and purification of human apolipoproteins A-I and A-II. PMID- 1904883 TI - Operation improvement: efficiencies and quality. PMID- 1904884 TI - An analysis of the quality and effectiveness of the discharge planning process. PMID- 1904885 TI - A critical literature review of alcoholism treatment cost-benefit/effectiveness. PMID- 1904886 TI - Cost containment: weaning of the cardiac surgical patient. PMID- 1904888 TI - Multiple miliary osteoma cutis. AB - We describe the clinical, radiographic, histologic, and metabolic features of an unusual case of multiple miliary osteoma cutis in an otherwise healthy 57-year old woman. Although the pathogenesis of this rarely reported entity is not fully understood, the novel application of a dynamic bone study revealed a high rate of internal bone remodeling within the lesion. This finding prompted a brief therapeutic trial of a diphosphonate, not previously reported in the treatment of this condition. PMID- 1904887 TI - Intracranial recordings of movement-related potentials to voluntary saccades. AB - Movement-related potentials evoked by voluntary and self-initiated horizontal saccades were recorded from subdural electrodes placed over the lateral (premotor and motor cortex) and the mesial (supplementary motor area) surfaces of the frontal lobe, in four patients with intractable focal seizures. An extremely localized bereitschaftspotential showing approximately the same latencies and amplitudes was simultaneously recorded from the frontal eye field and supplementary motor area (SMA). Our data suggest that both regions are equally active prior to saccades and do not support the view that the SMA acts as a supramotor cortex, being activated during the planning of the movement and the primary motor cortex only later on, close to the execution of the movement. In addition, we never observed the spike potential in our intracranial recordings, thus supporting the hypothesis of its extracerebral origin. PMID- 1904889 TI - Complement consumption in a patient with necrobiotic xanthogranuloma and paraproteinemia. AB - Necrobiotic xanthogranuloma and paraproteinemia have been reported to be associated with acquired deficiency of the early components of the classic pathway of complement. We describe a patient in whom activation of complement was suggested by a high level of C3d, an accelerated catabolism of C1q, and a rapid consumption of C4 after an intravenous infusion of fresh-frozen plasma. This infusion was followed by an episode of pulmonary edema. Patients with complement deficiency or depletion should be monitored closely while receiving plasma, to avoid this potential complication. PMID- 1904890 TI - Enamel surface roughness and dental pulp response to coaxial carbon dioxide neodymium: YAG laser irradiation. AB - The purpose of this study was to evaluate the effect of a coaxial carbon dioxide/neodymium:yttrium aluminium garnet laser beam on enamel surface roughness and the dental pulps of mongrel dogs. In four dogs, four maxillary left posterior teeth were irradiated at 16 cm source-tooth distances. Two teeth were irradiated with 16 W CO2/16 W Nd:YAG and the remaining two with 16 W CO2/40 W Nd:YAG. Two maxillary right teeth were untreated controls. In addition, mandibular premolars were irradiated at the same distance and power levels, extracted, and analysed for surface roughness. Significant differences in surface roughness were found between control samples and either power level, but not between enamel surfaces at the two power levels. Maxillary teeth were removed at 10 days postoperatively, sectioned and stained (H & E). The reaction of pulpal cells to irradiation was scored. Data analysis revealed statistically significant differences between the control and lower power Nd:YAG groups and between the control and higher power Nd:YAG groups. The difference in pulpal response between both laser groups approached significance. PMID- 1904891 TI - Events in the Cardiac Arrhythmia Suppression Trial (CAST): mortality in the entire population enrolled. AB - To test the hypothesis that suppression of ventricular arrhythmias by antiarrhythmic drugs after myocardial infarction improves survival, the Cardiac Arrhythmia Suppression Trial (CAST) was initiated. Suppression was evaluated before randomization during an open label titration period. Patients whose arrhythmias were suppressed were randomized in the main study and those whose arrhythmias were partially suppressed were randomized in a substudy. Overall survival and survival free of arrhythmic death or cardiac arrest were lower [corrected] in patients treated with encainide or flecainide than in patients treated with placebo. However, the death rate in patients randomized to placebo therapy was lower than expected. This report describes the survival experience of all patients enrolled in CAST and compares it with mortality in other studies of patients with ventricular arrhythmias after myocardial infarction. As of April 18, 1989, 2,371 patients had enrolled in CAST and entered prerandomization, open label titration: 1,913 (81%) were randomized to double-blind, placebo-controlled therapy (1,775 patients whose arrhythmias were suppressed and 138 patients whose arrhythmias were partially suppressed during open label titration); and 458 patients (19%) were not randomized because they were still in titration, had died during titration or had withdrawn. Including all patients who enrolled in CAST, the actuarial (Kaplan-Meier) estimate of 1-year mortality was 10.3%. To estimate the "natural" mortality rate of patients enrolled in CAST, an analysis was done that adjusted for deaths that might be attributable to encainide or flecainide treatment either during prerandomization, open label drug titration or after randomization. Because the censoring procedure excluded patients treated with encainide or flecainide after randomization, the mortality estimate will be less than the unadjusted mortality estimate of 10.3%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1904893 TI - Cardiac surgery in the octogenarian: perioperative outcome and clinical follow up. AB - The perioperative and follow-up results of cardiac operations employing extracorporeal circulation and cold cardioplegic arrest were examined in 191 consecutive patients greater than or equal to 80 years of age having surgery over a 5 year period (1982 to 1986). Most patients had severe preoperative symptoms with functional class III (39.8%) or IV (57.1%) limitation. The overall 30 day postoperative cardiac mortality rate was 15.7%. The total in-hospital mortality rate was 18.8%; the mean postoperative hospital stay was 16.4 +/- 13.3 days. The perioperative mortality rate for elective operations was as follows: coronary artery bypass (5.6%), aortic valve replacement (9.6%), aortic valve replacement with coronary bypass (17.9%) and mitral valve surgery with or without coronary bypass (21.4%). Urgent operations were performed in 39 patients (20.4%) with a total perioperative mortality rate of 35.9%; urgent coronary artery bypass was performed in 26 patients (67%) with an in-hospital mortality rate of 23.1%. Clinical evidence of left ventricular failure, functional class IV symptoms, left ventricular ejection fraction less than 50%, mitral valve repair or replacement for severe mitral regurgitation and urgent operation were associated with an increased perioperative mortality rate. Follow-up study in all 155 patients surviving postoperative hospitalization at 22.6 +/- 14.8 months showed significant improvement in symptom status in all surgical subgroups. There were 18 follow-up deaths (11.6%); 10 were noncardiac. The actuarial survival rate of the entire study group was significantly better than that in age- and gender matched control subjects (p = 0.037).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1904892 TI - Events in the Cardiac Arrhythmia Suppression Trial (CAST): mortality in patients surviving open label titration but not randomized to double-blind therapy. AB - The patient characteristics and outcomes were studied in the 318 patients who survived open label drug titration in the Cardiac Arrhythmia Suppression Trial (CAST) and who were not randomized to double-blind therapy and in 942 patients, who were randomized to double-blind placebo therapy. The patients randomized to placebo therapy had a lower total mortality or resuscitated cardiac arrest rate (4% vs. 8.5%). However, at baseline, nonrandomized patients were dissimilar from patients randomized to placebo in the following ways: older; lower left ventricular ejection fraction; greater use of digitalis, diuretic drugs and antihypertensive agents; lesser use of beta-adrenoceptor blocking agents and more frequent prior cardiac problems, including runs of ventricular tachycardia and left bundle branch block. A matched comparison that took these inequities into account showed no significant differences in mortality or rate of resuscitation from cardiac arrest between nonrandomized patients and clinically equivalent patients randomized to placebo. Cox regression analysis indicated that two factors significantly increased the hazard ratio for arrhythmic death or resuscitated cardiac arrest in the nonrandomized patients: female gender (4.7, p less than 0.05) and electrocardiographic events (ventricular tachycardia, proarrhythmia, widened QRS complex, heart block, bradycardia) during open label titration (7.0, p less than 0.005). However, some potentially important differences between men and women were not included in the Cox regression model. Of the nonrandomized patients, approximately 70% were not randomized because of lack of suppression of ventricular premature depolarizations or adverse events, or both, and the remaining 30% because of patient or private physician request with no indication of another reason.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1904894 TI - Renal cytochrome P-450-dependent metabolism of arachidonic acid in cirrhotic rats. AB - Cirrhosis was induced in Wistar-Kyoto rats by intragastric administration of carbon tetrachloride. Microsomes were obtained from the renal cortex and outer medulla and incubated with [14C]arachidonic acid (AA) (0.2-0.4 microCi) in the presence or absence of indomethacin, NADPH, and SKF-525A. Cytochrome P-450 dependent AA metabolites (those whose formation required NADPH, were inhibited by SKF-525A, but not by indomethacin) were separated by thin-layer chromatography and high-pressure liquid chromatography (HPLC). Compared to controls, total synthesis of cytochrome P-450-dependent AA metabolites was reduced in cirrhotic rats (renal cortex: cirrhotics 380 +/- 52 vs. controls 493 +/- 68 pg/mg protein per 30 min; p less than 0.05; renal outer medulla: cirrhotics 304 +/- 57 vs. controls 387 +/- 53 pg/mg protein per 30 min; p less than 0.05). The cytochrome P 450-dependent AA metabolites were composed of three peaks separated by HPLC. Peak I, which had a retention time of 16.3 +/- 0.3 min and comigrated with 11,12 dihydroxyeicosatrienoic acid, and peak II, which had a retention time of 18.7 +/- 0.4 min and comigrated with 19- and 20-hydroxyeicosatetraenoic acid, were not different in cirrhotics and controls. Peak III, which had a retention time of 26.8 +/- 0.3 min, and comigrated with 11,12-epoxyeicosatrienoic acid, was significantly decreased in the renal cortex of cirrhotic rats compared to controls (cirrhotics 316 +/- 40 vs. controls 473 +/- 89 pg/mg protein per 30 min; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1904895 TI - Autoimmune chronic hepatitis type 2 manifested during interferon therapy in children. PMID- 1904896 TI - The role of eicosanoids in the acute phase response. PMID- 1904897 TI - Rocky Mountain spotted fever. AB - Rocky Mountain spotted fever, the most prevalent rickettsial disease in the United States, is one of the most severe of all infectious diseases. It remains an important infectious disease because of its prevalence, the difficulty of clinical diagnosis, potentially fatal outcome, and lack of a widely available sensitive and specific diagnostic test during the acute stage of the illness. PMID- 1904898 TI - Extrathymic clonal deletion of self-reactive cells in athymic mice. AB - The repertoire of T cells present in congenitally athymic mice was studied by flow cytometric analysis on populations of T cells expanded polyclonally in vitro. Athymic (BALB/c x C57BL/6)F1 mice have levels of potentially autoreactive V beta 3- and V beta 11-bearing T cells that are significantly higher than those of euthymic CB6F1 mice. Examination of potentially autoreactive cells in athymic AKR mice, however, yielded contrasting results. V beta 6+ cells, which are deleted intrathymically in normal AKR mice, are present in the repertoire of young (less than 6-wk-old) AKR nu/nu mice. Isolation of a cloned CD4+V beta 6+ cell line with Mls-1a reactivity from young AKR nu/nu mice indicates that the correlation between TCR usage and specificity is consistent with that described in euthymic mice and that this population contains autoreactive T cells that are not anergic. By 6 mo of age, however, cells expressing V beta 6 are no longer detectable. Inability to detect these cells is not simply caused by failure to expand these cells in culture, because freshly isolated populations from old nude mice exhibit the same selective absence of V beta 6-bearing cells. The data strongly suggest that extrathymic deletion, rather than clonal anergy, accounts for the apparent absence of autoreactive V beta 6-bearing cells in aged AKR nu/nu mice. PMID- 1904899 TI - Nitric oxide production is required for murine resident peritoneal macrophages to suppress mitogen-stimulated T cell proliferation. Role of IFN-gamma in the induction of the nitric oxide-synthesizing pathway. AB - Lymphocyte proliferation in Con A- or LPS-stimulated murine splenic cell (SC) cultures was suppressed by the addition of excess macrophages. In Con A stimulated cultures, suppression was associated with the expression of nitric oxide-synthesizing pathway (NOSP) activity as demonstrated by the accumulation of nitrite, a degradation product of nitric oxide (NO), in the culture supernatants. That NO, a cytotoxic and anti-proliferative metabolite of l-arginine, or other reactive nitrogen intermediates generated through the NOSP mediated the suppressive effect was suggested by the reversal of suppression brought about by the addition of a specific inhibitor of the NOSP (NG-monomethyl-l-arginine acetate) to the culture media. No NOSP activity was detectable in LPS-stimulated SC/macrophage cocultures. The role of T cell-derived IFN-gamma in the induction of the NOSP was investigated by the use of anti-IFN-gamma-mAb. Antibody-treated Con A supernatants failed to induce the NOSP in macrophages, and the addition of the mAb to Con A-stimulated SC/macrophage cocultures obviated the suppressive effects. Indomethacin and catalase only partially restored proliferation in Con A stimulated SC/macrophage cocultures but were remarkably efficient in preventing macrophage-dependent suppression when LPS was used as the mitogenic stimulus. These results demonstrate a regulatory system of potential relevance in sites of predominant macrophage infiltration by which T cell-derived IFN-gamma activates the production of the mediator, NO, that suppresses T cell proliferation. In addition, these data demonstrate that, although the suppressive effects of excess macrophages appear to be expressed nonspecifically toward both T and B cells, suppression is mediated through a different mechanism in each case. PMID- 1904900 TI - Manganese superoxide dismutase is induced by IFN-gamma in multiple cell types. Synergistic induction by IFN-gamma and tumor necrosis factor or IL-1. AB - We have previously characterized more than 20 proteins induced by the immunoregulatory lymphokine IFN-gamma in human fibroblasts by their m.w. and isoelectric points determined in two-dimensional gels. Some of these proteins are induced uniquely by IFN-gamma, whereas others are also induced by IFN-alpha, TNF, or IL-1. Recent technologic advances have allowed us to begin to rapidly identify proteins induced by IFN-gamma and other cytokines by sequencing the induced proteins from blots of preparative two-dimensional gels of total cell lysates. In this study, we show that the approximately 21 kDa, isoelectric point greater than 7 protein induced by IFN-gamma is manganese superoxide dismutase (Mn-SOD), a mitochondrial protective enzyme encoded by a nuclear gene. Mn-SOD is induced by IFN-gamma and also by TNF in all four human cell lines examined: HS153 fibroblasts, ACHN renal carcinoma, A549 lung carcinoma, and A375 melanoma. Induction of Mn-SOD mRNA is a primary, rapid, and dose-dependent response to IFN gamma. In ACHN renal carcinoma cells, Mn-SOD mRNA and protein are induced synergistically by IFN-gamma in combination with either TNF or IL-1, and the induced protein is enzymatically active. IFN-gamma and TNF together induce Mn-SOD mRNA by more than 100-fold relative to its level in untreated ACHN cells. The induction of Mn-SOD by IFN-gamma and its synergistic induction by IFN-gamma in combination with TNF and IL-1 should protect healthy cells from the toxicity of O2- during an immune response, and may provide a mechanism for selective killing of infected cells. PMID- 1904901 TI - Quantitative analysis of adenine nucleotides during the prelytic phase of cell death mediated by C5b-9. AB - The nucleated cell death mediated by C5b-9 depends on the extent of C fixation and parameters that affect the ability of the cell to eliminate C5b-9. When C5b-9 formation exceeds elimination, cell death can be initiated. High Ca2+ in the medium accelerates Ehrlich ascites cell death induced by a large number of C5b-9, whereas osmotic prevention of cell swelling has little effect in protecting Ehrlich cells from killing by C5b-9. In the present study, we investigated the interrelationship between intracellular Ca2+, intra- and extracellular adenine nucleotides, and mitochondrial membrane potential, to understand the mechanism of acute cell death induced by C5b-9. When Ehrlich cells carrying C5b-8 were exposed to C9, rapid and profound ATP depletion in the cell was observed before cell death. Leakage of the adenine nucleotides ATP, ADP, and AMP also began during the prelytic phase. Studies using digital imaging fluorescence microscopy showed that loss of mitochondrial membrane potential was noted immediately after C9 addition but before nuclear staining with propidium iodide. These findings suggest that an increase in intracellular Ca2+ through C5b-9 channels and loss of mitochondrial membrane potential may initiate rapid cell death. The prelytic leakage of ATP precursors may also contribute to cell death by decreasing nucleotide pools, because recovery of ATP production was observed after a similar degree of ATP loss in cells exposed to sublethal doses of KCN, in which ADP and AMP leakage was not present. PMID- 1904902 TI - Soluble IL-2 receptor as an agent of serum-mediated suppression in human visceral leishmaniasis. AB - In visceral leishmaniasis (VL), patient's lymphocytes are not activated by leishmania Ag stimulation, and their sera exhibit a potent nonspecific suppressive effect on the responses of normal lymphocytes. Sera were obtained from 33 VL patients, eight patients with subclinical VL, and from 27 normal volunteers. Only sera from VL patients markedly reduced Con A-induced lymphocyte proliferative responses, as well as IL-2 or IFN-gamma production by normal lymphocytes. Addition of exogenous human rIL-2 to cultures containing VL patient sera partially reversed the normal lymphocyte proliferative capacity and restored IFN-gamma production. This phenomenon was consistent with the presence of greatly elevated levels of soluble IL-2R (sIL-2R) in VL patients' sera (4299 +/- 2351 U/ml), well above those of normal sera (180 +/- 94 U/ml), or of sera from patients with subclinical leishmania infection without immunosuppression (1002 +/ 281 U/ml). Furthermore, the removal of sIL-2R reduced VL serum suppressive activity as evaluated by effects on IL-2 and on IFN-gamma production. These data suggest the participation of high levels of sIL-2R in the serum-mediated suppression in VL. PMID- 1904903 TI - Immune response to Schistosoma mansoni infections in inbred rats. VII. Resistance is contingent on OX-8(+)-regulated high affinity IL-2 receptor-bearing W3/25+ lymphocytes but not on IL-4-dependent cells. AB - These studies assess the roles of subpopulations of T lymphocytes in resistance to Schistosoma mansoni. CDF rats were depleted of the T cell subpopulation bearing the high affinity IL-2R by in vivo treatment with ART18+ mAb or of soluble IL-4 by treatment with 11B11 mAb. The development of parasites, the expression of resistance after sensitization, and the intensity of delayed type hypersensitivity (DTH), Ag-mediated blast transformation (AMBT), IgG2a, passive cutaneous anaphylaxis, and IgE-mediated antibody-dependent cell-mediated cytotoxicity responses against S. mansoni or control Ag were ascertained. Isolated T cell subpopulations were assessed in vivo and in vitro for effects upon the protective Ir. Depletion with ART18 mAb suppressed the development of W3/25+ helper-inducer cells and resulted in the initial survival of more worms, decreased resistance to challenge after initial sensitization, decreased IgG2a and IgE antibody, AMBT, and DTH reactivity against schistosome Ag. Depletion with ART18 did not prevent the development of OX8+ (T suppressor) cells. Depletion with 11B11 mAb led to insignificant changes in initial parasite survival and resistance to challenge; had no effect on IgG2a antibody, AMBT, or DTH; but profoundly suppressed the IgE responses against the parasite. Protective immunity to S. mansoni in rats is dependent upon IL-2R-bearing T lymphocytes and regulated by OX8+ cells but not absolutely contingent upon IL-4 or the IgE response. PMID- 1904905 TI - Ultrastructural examination of experimentally induced premalignant lesions. AB - Lesions induced in hamster cheek pouch using dimethylbenz(alpha)anthracene were studied by transmission electron microscopy and compared with normal tissue. Features regarded as suggestive of progression towards malignancy were: increased numbers of membrane-bound vesicles in basal cells, gaps in the lamina densa associated with widening of the lamina lucida and an irregular epithelial connective tissue junction, the presence of cerebriform cells and frequent close association of 2 or more intra-epithelial cells (lymphocytes, cerebriform cells, Langerhans cells). PMID- 1904904 TI - IFN-gamma reverses IL-4 inhibition of fetal thymus growth in organ culture. AB - IL-4 is known to inhibit the growth and differentiation of 14-day-old fetal mouse thymus in organ culture. Here we report that IFN-gamma reverses this IL-4 mediated growth inhibition. Thymus lobes from 14-day-old fetuses were cultured for 12 days in medium containing 100 IU/ml rIL-4 either in the absence or presence of rIFN-gamma (100 to 1000 IU/ml). After culture, the cell yields and the absolute numbers and frequencies of the major subpopulations according the coordinate expression of CD4 and CD8 were estimated. IL-4 treatment alone was found to result in a seven-fold decrease in cell yield and an almost complete absence of the CD4+CD8+ subpopulation. Addition of IFN-gamma reversed IL-4 mediated inhibition in a dose-dependent fashion, with an optimal dose ranging from 200 to 500 IU/ml. IFN-gamma exerted this effect only when added within the first 48 h of initiating the culture. The specificity of the reversal effect was ascertained by neutralization of the effect by a neutralizing anti-IFN-gamma mAb and by lack of activity of human IFN-gamma. In the absence of IL-4, IFN-gamma had a growth-promoting effect as evident from a threefold increase in cell numbers. PMID- 1904907 TI - Antiproliferative effects of natural human tumor necrosis factor-alpha, interferon-alpha, and interferon-gamma on human pancreatic carcinoma cell lines. AB - The antiproliferative effects of natural human tumor necrosis factor-alpha (nHuTNF-alpha), natural human interferon-alpha (nHuIFN-alpha), and natural human interferon-gamma (nHuIFN-gamma) were investigated in human pancreatic carcinoma cell lines. HuP-T3, HuP-T4, and BxPC-3 carcinoma cells exhibited mild growth inhibition after treatment with nHuTNF-alpha. HuP-T3, HuP-T4, MIA-PaCa-2, and BxPC-3 cells exhibited mild or marked growth inhibition after treatment with nHuIFN-alpha. Incubation with nHuIFN-gamma caused marked growth inhibition of HuP T4 and BxPC-3 cells, whereas HuP-T1, HuP-T3, and MIA-PaCa-2 cells showed only mild growth inhibition with the same dose of nHuIFN-gamma. Combined nHuTNF-alpha and nHuIFN-alpha (1:1) demonstrated marked synergism in comparison with their effects as single agents on HuP-T1, HuP-T3, and MIA-PaCa-2 cells. The combination of nHuTNF-alpha and nHuIFN-gamma (100:1) also demonstrated a marked synergistic effect in comparison with these cytokines alone in four out of five pancreatic carcinoma cell lines (HuP-T1, HuP-T3, HuP-T4, and MIA-PaCa-2 cell lines). The marked increase in efficacy brought about by using combinations of cytokines may enable some improvement in the treatment of pancreatic carcinoma patients in the future. PMID- 1904906 TI - Reconstruction of orbital floor with polydioxanone plate. AB - The use of a polydioxanone (PDS) plate for orbital reconstruction was evaluated in 20 patients with various traumatic defects of the orbital floor. The follow-up time was 9 to 45 months (mean 20.4 months). A CT scan was obtained in 13 patients. Radiographic analysis showed that in 12 of the 13 patients there was new bone in the orbital floor. Clinically, most patients had transitory postoperative diplopia (lasting for a mean of 29 days) because of overcorrection. Only 2 patients, however, suffered from persistent diplopia. In one patient, abducens nerve paresis was the cause. It is concluded that PDS is suitable for orbital floor reconstruction, at least in cases in which defects do not exceed 1 2 cm in diameter. Overcorrection seems necessary. The material is well tolerated, is totally absorbed and appears to be replaced by bone in nearly all cases. PMID- 1904908 TI - Treatment of bulimia nervosa with lithium carbonate. A controlled study. AB - Ninety-one female bulimic outpatients received lithium carbonate or placebo on a random basis, after being separated into depressed and nondepressed subgroups, in an 8-week double-blind trial. Sixty-eight patients who completed the study experienced a significant decrease in bulimic episodes after the 8 weeks. Lithium, in a dosage yielding relatively low plasma levels, was not more effective than placebo. However, depression and other psychopathologies decreased with improvement in bulimic behavior. PMID- 1904909 TI - Biosynthesis of prostaglandins D2 and E2 in chick dorsal root ganglion during development. AB - Newly formed prostaglandins (PGs), which are assumed to act as modulators of afferent sensory messages, were studied in chick dorsal root ganglia (DRG) during development. [1-14C]Arachidonic acid was converted by DRG homogenates from 1-week old chickens into two major 14C-PGs: PGE2 and PGD2. The enzymatic conversion of arachidonic acid was characterized as follows: (a) Boiled preparations were inactivated; (b) synthesis of PGs was inhibited by pretreatment with aspirin or indomethacin and enhanced by esculetin, a protector of cyclooxygenase; and (c) [14C]PGE2 and [14C]PGD2 accumulation was a protein dose-dependent process. Further fractionation of crude homogenates indicated that PG endoperoxide synthetase (EC 1.14.99.1) and PGE2 synthetase (EC 5.3.99.3) were membrane-bound enzymes, whereas PGD2 synthetase (EC 5.3.99.2) was recovered in the cytosol. During development, from embryonic day 10 to day 14 after hatching, PGD2 synthetase activity remained constant; in contrast, a sharp rise in [14C]PGE2 synthesis was observed from embryonic day 14 to 18. The time curves of PGD2 and PGE2 synthetase specific activity may be related to changes taking place in the cell population of developing DRG. It is therefore suggested that arachidonic acid would be enzymatically converted early into PGD2 by maturing ganglion cells and then later into PGE2 by proliferating fibroblasts. PMID- 1904910 TI - Detection of G proteins in purified bovine brain myelin. AB - Following a previous report on detection of muscarinic receptors in myelin with the implied presence of G proteins, we now demonstrate by more direct means the presence of such proteins and their quantification. Using [35S]guanosine 5'-O-(3 thiotriphosphate) ([35S]GTP gamma S) as the binding ligand, purified myelin from bovine brain was found to contain approximately half the binding activity of whole white matter (138 +/- 9 vs. 271 +/- 18 pmol/mg of protein). Scatchard analysis of saturation binding data revealed two slopes, a result suggesting at least two binding populations. This binding was inhibited by GTP and its analog but not by 5'-adenylylimidodiphosphate [App(NH)p], GMP, or UTP. Following sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis (PAGE) of myelin proteins and blotting on nitrocellulose, [alpha-32P]GTP bound to three bands in the 21-27-kDa range in a manner inhibited by GTP and GTP gamma S but not App(NH)p. ADP-ribosylation of myelin with [32P]NAD+ and cholera toxin labeled a protein of 43 kDa, whereas reaction with pertussis toxin labeled two components of 40 kDa. Cholate extract of myelin subjected to chromatography on a column of phenyl-Sepharose gave at least three major peaks of [35S]GTP gamma S binding activity. SDS-PAGE and immunoblot analyses of peak I indicated the presence of Go alpha, Gi alpha, and Gs alpha. Further fractionation of peak II by diethyl aminoethyl-Sephacel chromatography gave one [35S]GTP gamma S binding peak with the low-molecular-mass (21-27 kDa) proteins and a second showing two major protein bands of 36 and 40 kDa on SDS-PAGE.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1904911 TI - Robustness of G proteins in Alzheimer's disease: an immunoblot study. AB - Many of the neurotransmitter systems that are altered in senile dementia of the Alzheimer type are known to mediate their effects via G proteins, yet the integrity of guanine nucleotide-binding proteins (G proteins) in Alzheimer's diseased brains has received minimal investigation. The aim of this study was to establish whether the level of G alpha subunits of five G proteins was altered in Alzheimer's disease. We used immunoblotting (Western blotting) to compare the amounts of Gi1, Gi2, GsH (heavy molecular weight), GsL (light molecular weight), and Go in the frontal cortex and hippocampus, two regions severely affected by the disease, and the cerebellum, which is less severely affected. The number of senile plaques was also quantified. We report that there was no significant difference in the level of these G alpha subunits between Alzheimer's diseased and age-matched postmortem brains. These results suggest that alterations in the amount of G protein alpha subunits are not a feature of Alzheimer's disease. PMID- 1904912 TI - Interaction of regrowing PNS axons with transplanted aggregates of cultured CNS glia in vivo. AB - Aggregates of cultured neonatal mouse cerebellar astrocytes were implanted into adult mouse sciatic nerves. Two different experimental models were used: aggregates were either placed between proximal and distal stumps of totally transected nerves, or were placed in gaps in partially transected nerves in direct apposition with the cut surface of the proximal stumps. In the model where aggregates were not placed in contact with the proximal stump, regrowing axons rarely entered the aggregates. Where aggregates were placed in contact with the proximal stumps, axons entered the astrocyte-rich environment. Experimental depression of the supply of Schwann cells available to comigrate with regenerating axons proved to be unnecessary: astrocytes provided an alternative substrate for axons. Some axons became myelinated by oligodendrocytes which differentiated within the aggregates; however, few axons remained, unmyelinated, in long-term association with the transplanted astrocytes. PMID- 1904914 TI - Evaluation of energy sources with and without carnitine in newborn pig heart and liver. AB - The oxidation rate of five energy substrates with and without exogenous addition of carnitine in the heart and liver of 15-h-old nonsuckled piglets was evaluated. Oxygen consumption (nmol O2.mg protein-1.min-1) in heart and liver for five substrates were: pyruvate, 0.248, 0.191; palmitoyl-CoA, 0.042, 0.034; palmitoyl carnitine, 0.249, 0.111; isovalerate, 0.084, 0.059; acetoacetate, 0.166, 0.068, respectively. The addition of free carnitine doubled the rate of palmitoyl-CoA utilization in both heart and liver, but palmitoyl-CoA oxidation was always much lower than that of palmitoyl-carnitine. In livers of piglets from sows fed 8% fat, palmitoyl-carnitine oxidation was slower (P less than 0.03) than in piglets from sows fed 0% fat. Heart tissue metabolized isovalerate faster (P less than 0.02) when piglets were from sows fed fat compared with those from the nonfat group. A lysine x fat interaction was observed for piglet liver metabolism of isovalerate and acetoacetate, suggesting that a more metabolically developed pig results when sows are fed 0.48% lysine without supplemental fat during gestation. Carnitine did not seem to be the limiting factor for the oxidation of palmitoyl CoA, and gestational dietary fat and lysine seemed to influence substrate metabolism in the newborn pig. PMID- 1904913 TI - Characterization of the electroantennogram in Drosophila melanogaster and its use for identifying olfactory capture and transduction mutants. AB - 1. Amplitude as well as time course of the electroantennogram (EAG) in Drosophila has been used for describing electrical changes produced in the antenna in response to odorous stimulation. 2. Maximal amplitude of response appears to be directly correlated to stimulus concentration but, after achieving a maximum value, is independent of stimulation duration. 3. Rise time and fall time constants have been quantified for describing kinetics of response. The rise time constant decreases, but the fall time constant increases when increasing concentrations of odorant are supplied. 4. Variation among individuals for these EAG parameters is small enough to uncover even partial defects affecting the first sensory step. This fact combined with the possibility of obtaining mutants with defects in any intermediate process producing the electrical response makes the EAG of Drosophila a very useful tool for dissecting the components of the capture and transduction processes in the olfactory sense. 5. This kind of quantitative study of the EAG has been used in a new Drosophila mutant, od A, for localizing peripheral expression of the mutation. od A has been isolated as a behavioral mutant with an abnormally enhanced olfactory response to ethyl acetate. 6. The mutant's EAG in response to this odorant displays a normal amplitude but abnormal kinetics. Rise time as well as fall time show slower kinetics than normal, suggesting some defective step in the capture and transduction process. PMID- 1904916 TI - The effect of etching on glass polyalkenoate cements. AB - The effect of acid etching on the surface appearance and flexural strength of four glass polyalkenoate cements was investigated. Specimens were etched for intervals of 10-60 s, both at the recommended time after mixing and after a 24-h delay. The surface texture was examined microscopically. Further specimens were subjected to a 4-point bend test following etching 1 h and 24 h after mixing. Deterioration of the surface appearance occurred as the etching time was increased beyond 10 s following immediate etching. Etching after 24 h reduced surface damage, but a 10-s etch still gave the most favourable surface appearance without loss of particulate material. Etching beyond 10 s significantly reduces flexural strength. PMID- 1904915 TI - Alteration of serum lipoprotein metabolism by polychlorinated biphenyls and methionine in rats fed a soybean protein diet. AB - The effects of dietary supplementation of methionine to a 20% soybean protein isolate diet on serum lipoprotein profiles and secretion rate of VLDL in rats receiving polychlorinated biphenyls (PCB) were investigated. Serum cholesterol levels were higher in rats fed PCB or a methionine supplement than in controls. The effects of PCB and methionine were synergistic. The feeding of PCB resulted in more cholesterol in all fractions of serum lipoproteins tested, especially HDL (HDL1 and HDL2). Dietary supplementation of methionine primarily increased HDL cholesterol. The elevation of serum lipoprotein cholesterol due to PCB and/or methionine was significant in HDL1, which showed alpha-mobility. These results showed that methionine and PCB significantly influenced HDL metabolism. The secretion rate of VLDL was higher in rats fed PCB than in controls, but the addition of methionine to diets did not affect the secretion rate of VLDL cholesterol. This implies that PCB increased serum cholesterol partly through the stimulation of VLDL cholesterol secretion. PMID- 1904917 TI - Photochemical and photosensitizing properties of monomeric and dimeric Sn(IV) protoporphyrin. AB - Sn(IV)-protoporphyrin IX (Sn-Pp) in aqueous media exists as a mixture of monomeric and dimeric species, which can be readily distinguished on the basis of their absorption maxima at around 410 and 386 nm respectively. Sn-Pp dimers prevail as the pH is decreased and are characterized by a lower fluorescence quantum yield, a larger tendency to undergo photobleaching and a reduced photosensitizing efficiency compared with the Sn-Pp monomer. The photosensitizing action of Sn-Pp appears to involve the intermediacy of singlet oxygen (1O2) as shown by photo-oxidation studies with N-acetyl-tryptophanamide in light and deuterated water solutions. Using 1,3-diphenyl-isobenzofuran as a substrate, the quantum yield of 1O2 generation by monomeric Sn-Pp was found to be about 0.6. PMID- 1904918 TI - Luminescence spectra of exponential and stationary phase cultures of respiratory deficient Saccharomyces cerevisiae. AB - The spectral distributions of the luminescences emitted by the respiratory deficient mutant of Saccharomyces cerevisiae and the normal yeast have been determined during the exponential phase of growth and during the stationary phase. The respiratory-deficient mutant gave a more intense emission in the visible region than did the normal yeast, but the UV intensities from the two yeasts did not differ greatly. These differences were explained in terms of higher O2- concentrations in the respiratory-deficient mutant which lead to enhanced visible region chemiluminescence from lipid peroxidation reactions. PMID- 1904921 TI - Photodegradation or piroxicam under aerobic conditions. The photochemical keys of the piroxicam enigma? PMID- 1904919 TI - Coloured complexes of all-trans-retinal with benzocaine and other local anaesthetics. AB - Coloured Schiff base complexes with lambda max values of 500 nm or above were formed between the visual pigment all-trans-retinal and the local anesthetics procaine (lambda max = 533 nm), benzocaine (4-amino-benzoic acid ethyl ester, lambda max = 535 nm), 3-amino-benzoic acid ethyl ester (lambda max = 500 nm) and 2-amino-benzoic acid ethyl ester (lambda max = 509 nm) in methanol acidified with HCl. The anaesthetics lidocaine and urethane failed to form coloured compounds with lambda max values greater than 500 nm under the same conditions. The relevance of these observations to the effect of anaesthetics on the visual pigments is discussed. PMID- 1904922 TI - Role of tocopherols in the protection of biological systems against oxidative damage. PMID- 1904920 TI - Isolation and protein chemical characterization of the B806-866 antenna complex of the green thermophilic bacterium Chloroflexus aurantiacus. AB - The B806-866 antenna complex was isolated from cytoplasmic membranes of the green thermophilic bacterium Chloroflexus aurantiacus. The membranes were treated with 7 M urea at 50 degrees C, the B806-866 antenna complex was solubilized with a mixture of Noni-fjdet P-40 (octylphenoxypolyethoxyethanol (Sigma)) and sodium dodecylsulphate (2:1) and isolated by sucrose density gradient centrifugation. This antenna complex was characterized by reversed-phase chromatography (fast polypeptide and polynucleotide liquid chromatography), amino acid and sequence analyses. The B806-866 antenna of Chloroflexus aurantiacus consists of two polypeptides: the B806-866-alpha and B806-866-beta polypeptides in an apparent stoichiometric ratio of 1:1, which may be equivalent to the structural elementary unit found in the antenna systems of many species of Rhodospirillaceae. PMID- 1904923 TI - Tanning with UVB or UVA: an appraisal of risks. PMID- 1904924 TI - Of what value is a highly absorbing photosensitizer in PDT? PMID- 1904925 TI - Photosensitizing action of furocoumarins on membrane components and consequent intracellular events. AB - The photodamage induced in membrane components by furocoumarins is reviewed. The oxygen-dependent photoreactions between furocoumarins and cell membrane constituents lead mainly to lipid peroxidation and the formation of cross-linking in ghost proteins, whereas the oxygen-independent photoreactions lead essentially to a C4 cycloaddition between the furocoumarin and the unsaturated fatty acids. In the latter, cycloadducts are formed between the 3,4 double bond of the furocoumarin and the olefinic double bond of the unsaturated fatty acid. The stereochemical structures of these cycloadducts and the reaction mechanism of the cycloaddition are discussed. Finally, the modulation of several membrane systems by furocoumarins and the consequent intracellular events are reviewed. PMID- 1904926 TI - Sodium and potassium in the lens after exposure to radiation in the 300 nm wavelength region. AB - The possible change in sodium and potassium concentration in the lens after an in vivo exposure to radiation in the 300 nm wavelength region was investigated. Both lenses from 12 reference rats and from 80 unilaterally exposed rats were examined. The exposed rats were sacrificed in four groups: 6, 24, 72 and 168 h after exposure. The lenticular cation contents were determined using atomic absorption spectrophotometry. In exposed lenses the concentration of sodium increases whereas that of potassium decreases as the time after exposure increases. The rates of concentration change decrease as the time after exposure increases. The increase in sodium precedes the decrease in potassium. Furthermore, a slight increase in the concentration of sodium is registered, as the time after exposure increases, in the non-exposed contralateral lenses. The registered changes are believed to reflect the water balance in the lenses. PMID- 1904927 TI - Photoinduced interaction of thionine with phospholipid and cholesterol in artificial membranes. AB - The photoinduced interaction of thionine dye with phosphatidylcholine (PC) (and its components, e.g. lysoPC, phosphorylcholine and choline) and oxidized cholesterol was studied in artificial membranes using spectrophotometric and photoelectrochemical methods. The results show that the dye (electron acceptor) in its singlet excited state forms 1:1 electron donor-acceptor (EDA) complexes with the lipids (electron donor). The electrode kinetics of the photoinduced redox reactions in the cell were also studied to confirm the mechanism of photoinduced interaction between the dye and the lipid. PMID- 1904928 TI - Photosensitized damage of bilayer lipid membrane in the presence of haematoporphyrin dimethylether. AB - The variations in electrical conductivity and surface tension of planar bilayer lipid membranes (BLMs) sensitized by a haematoporphyrin dimethylether (HpDME) on visible light irradiation are reported. The irradiation of BLMs immediately leads to a decrease in membrane surface tension. On irradiation the conductivity of BLMs remains constant for a certain period of time (induction time), followed by an increase, terminated by membrane breakage. The induction time is not dependent on stirring of the solution, the addition of azide or ferricyanide to the solution, the addition of antioxidant to the lipid or substitution of air for argon in the cell. The induction time decreases for repeated irradiations or for any new BLM formed in the same cell immediately after the previous membrane has been broken. The conductivity shift consists of reversible and irreversible components. These results suggest that the irradiation of BLMs sensitized by HpDME leads to an accumulation of photoproducts in the membrane which induce pore formation and to a decrease in BLM stability when the concentration of the photoproducts exceeds a critical level. PMID- 1904929 TI - Inflammation and photodynamic therapy. PMID- 1904930 TI - Comment on "A guide to the terminology of hematoporphyrin-catalyzed photosensitization" (Michael A. J. Rodgers, J. Photochem. Photobiol., B: Biol., 5 (1990) 525)--a comment. PMID- 1904931 TI - Vial breakage by frozen mannitol solutions: correlation with thermal characteristics and effect of stereoisomerism, additives, and vial configuration. AB - The thermal characteristics as a function of cooling rate of mannitol solutions were studied by Differential Scanning Calorimetry (DSC). The exotherm appearing during warming at -25 +/- 1 degree C could be correlated with the temperature at which frozen mannitol solutions broke vials during warming. This temperature was also consistent with the temperature at which a sharp increase in resistance was reported in a preceding paper. The DSC exotherm did not appear to be due to crystallization of amorphous mannitol but rather to some other type of solid state transition. The peak was initially broadened and then obliterated by increasing amounts of additives such as lactose, glycine, potassium chloride, and sodium chloride. The presence of these ingredients in small amounts (less than 1% of the mannitol concentration) significantly reduced or prevented breakage. Other stereoisomers of mannitol, e.g., sorbitol and dulcitol, did not show any exotherm or break vials on freezing and thawing. It was also found that different types of vials exhibited different susceptibilities to breakage. PMID- 1904932 TI - Chronic diarrhea and malnutrition--histology of the small intestinal lesion. AB - The purpose of this study was to quantitate the jejunal lesion in Gambian children with chronic diarrhea-malnutrition syndrome. There were 40 subjects (20 male, 20 female) with a mean age of 19.7 months. All were severely malnourished, with marasmus in 30, marasmic kwashiorkor in 9, and kwashiorkor in 1. Of subjects tested, 70% were anergic to intradermal challenge with either purified protein derivative or candidin. Jejunal biopsies, performed on every subject after admission to hospital, were studied by computerised image analysis and immunocytochemistry. A spectrum of mucosal changes that varied from "normal" to "flat" was seen. Mucosae with "normal" architecture revealed infiltration of villous epithelium by small lymphocytes, while crypt hypertrophy was invariably present. At the other extreme, the surface epithelium of flat mucosae was less severely infiltrated, although heavy lymphoid infiltrates persisted within crypt epithelium. Immunohistochemical studies revealed that most intraepithelial lymphocytes were of the CD8 + phenotype. Mucosal morphology did not relate to clinical, biochemical, or anthropometric data for each child. These findings are consistent with an intestinal reaction to some environmental antigen (dietary, microbial, or both) of the cell-mediated type. This interpretation is strengthened by the expression of major histocompatibility class 2D locus alloantigens on crypt epithelial cells in the absence of gut-reactive autoantibodies. PMID- 1904933 TI - Human intestinal disaccharidase activities: correlations with age, biopsy technique, and degree of villus atrophy. AB - The relationship between intestinal morphology, disaccharidase activity, and disaccharide absorption is controversial. A retrospective study of 798 consecutive biopsies was performed to determine whether disaccharidase activities varied by subject age, biopsy technique, and degree of villus atrophy. Lactase activity was inversely correlated with age in the absence or presence of villus atrophy; sucrase, maltase, and palatinase activities did not correlate with age. Biopsies obtained by capsule or endoscopy had similar disaccharidase activities. In subjects 24 months of age or younger, the degree of mucosal injury was inversely correlated with lactase activity. In subjects older than 24 months, the degree of mucosal injury was inversely correlated with maltase and, to a lesser extent, lactase activities. The data suggest that disaccharidase activities in mucosal biopsies, whether obtained by endoscopy or capsule, are diminished in the presence of mucosal injury and correlate inversely with the degree of injury. PMID- 1904935 TI - Improvement of nutritional status in cholestatic children with supplemental nocturnal enteral nutrition. AB - Protein energy malnutrition is a common complication in cholestatic children in a hepatic transplant program, and may be detrimental to the postoperative outcome. Improvement of the nutritional status may be of obvious importance to improve the prognosis. This study compared oral nutrition with oral nutrition supplemented with nocturnal enteral feeding in children with prolonged cholestasis. In six children with prolonged cholestasis (conjugated bilirubin over 25 mg/L and/or GGT over 110 IU/L in infants aged less than 3 months or over 50 IU/L in older infants and/or alkaline phosphatase over 500 IU/L, for more than 3 months), we compared a 4 to 6 month period with oral nutrition and similar periods with 10 to 12 h nocturnal enteral feeding given at home as an energetic supplement. Energy intake during the second period was 180-200% of recommended dietary allowances. No ascites was found in the six patients during the study period. The Z scores of body weight, weight expressed as percent of ideal body weight (IBW), weight/height2, and arm circumference/head circumference were calculated at the beginning and at the end of each period. With only oral nutrition, a diminution in percentage of ideal W/H and a diminution in Z score for the body weight were observed in five of six patients. At the end of the second period, the average of all of the nutritional indexes was increased and the Z score for the body weight was also increased in four of six patients. Significant statistical differences (p less than 0.05) were found in W as percentage of IBW and the Z score for log W/H2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1904934 TI - Clinical application of a simple HPLC method for the sugar intestinal permeability test. AB - A new high pressure liquid chromatography (HPLC) method has been used to measure urinary sugar levels for the intestinal permeability test with cellobiose and mannitol (C/M test). Urinary specimens have been prepared by simple filtration through a Millipore membrane. The method is highly sensitive (minimal detectable concentration of urinary sugars = 0.01 mg/ml) and reproducible (coefficient variation between samples = 0.47% for cellobiose and 0.25% for mannitol). By this method a C/M test has been performed in a large series of gastroenterological patients. High values of mean urinary C/M percentage recovery ratio (C/M%) were found in 30 children with active gluten-sensitive enteropathy compared with controls (0.42 +/- 0.66 versus 0.014 +/- 0.005). In 44 treated celiacs and 34 children with chronic nonspecific diarrhea the mean C/M%s were 0.027 +/- 0.018 and 0.021 +/- 0.012, respectively. The results of this study confirm that the C/M test is a valuable investigation in the diagnostic studies of children with chronic diarrhea. The simple HPLC method described for the determination of urinary sugar levels should allow a wider diffusion of this test. PMID- 1904936 TI - Action of gold sodium thiomalate on experimental thrombosis in vivo. AB - In order to study the effect of gold compounds on the action of thrombin in vivo, experiments were performed to measure platelet survival and the weight of thrombus formation in experimental models of intra-aortic thrombosis by two indwelling aortic catheter methods. We have called these the long and short catheter methods. Platelet survival was reduced in all gold-treated and control animals which had indwelling aortic catheters. In the long catheter model, New Zealand White male rabbits were treated with one of the following: gold sodium thiomalate, sterile water, gold thioglucose, gold sodium thiosulfate, disodium thiomalate. Gold sodium thiomalate-treated rabbits had a reduced weight of experimentally induced intra-aortic thrombi compared with animals treated with sterile water or equimolar concentrations of gold thioglucose, gold sodium thiosulfate, or disodium thiomalate. This reduction in thrombus weight in the animals treated with gold sodium thiomalate was not reflected by changes in platelet survival or fibrinolysis. The serum gold levels achieved in these in vivo experiments was in the range of 5.0 X 10(-5) to 1.0 X 10(-4) M. These values are comparable to levels which can be achieved in human subjects immediately after a gold injection. In the short catheter model, New Zealand White male rabbits were treated with either gold sodium thiomalate, gold thioglucose, disodium thiomalate, or auranofin. Controls were given either water or 0.05% chlorocresol. Water-treated and gold sodium thiomalate-treated animals were also given 51Cr-labeled platelets and 125I-fibrinogen before insertion of the catheter.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1904937 TI - An evaluation of dental stones after repeated exposure to spray disinfectants. Part I: Abrasion and compressive strength. AB - This study investigated the effect of repeated applications of spray disinfectants on gypsum surfaces. Types III and IV gypsum products were evaluated in combination with iodophor, acid glutaraldehyde, phenol, and water spray. Results demonstrated greater resistance to abrasion with increasing numbers of water or disinfectant spray applications. Acid glutaraldehyde spray decreased the compressive strength of type III stone by 26%, phenol increased the compressive strength of type IV stone by 18%, and iodophor had no significant effect on either stone relative to compressive strength. PMID- 1904938 TI - Results of posterior tibial nerve grafting at the ankle. AB - The results of interfascicular interposition nerve grafting for posterior tibial nerve deficit at the ankle are reported for eight patients. The sural nerve was the donor nerve in all cases. Mean age at injury was 36.3 years (range 22 to 50 years). Mean postoperative follow-up is 5.0 years (range 2.25 to 8.0 years). In five of the patients, the primary indication for nerve grafting was pain or numbness in degree sufficient to consider amputation. Mean graft length was 9.8 cm (range 4 to 18 cm). After grafting, all eight patients ambulate without assistive devices and are productively employed or have resumed pre-injury household activities. All patients received postoperative sensory re-education. Sensory recovery has been to S4 level in two, to S3+ in four, and to S3 in two. There have been no foot ulcerations. It is concluded that grafting the posterior tibial nerve is indicated for the treatment of pain and recovery of sensation in carefully selected patients, and is capable of predictability restoring at least some touch sensibility. PMID- 1904939 TI - Measurement of exofacially reactive lysines on human erythrocyte band 3 using pyridoxal 5'-phosphate. PMID- 1904940 TI - Secondary structure constraints on the evolution of Drosophila 28 S ribosomal RNA expansion segments. AB - Eukaryotic ribosomal RNA genes contain rapidly evolving regions of unknown function termed expansion segments. We present the comparative analysis of the primary and secondary structure of two expansion segments from the large subunit rRNA gene of ten species of Drosophila and the tsetse fly species Glossina morsitans morsitans. At the primary sequence level, most of the differences observed in the sequences obtained are single base substitutions. This is in marked contrast with observations in vertebrate species in which the insertion or deletion of repetitive motifs, probably generated by a DNA-slippage mechanism, is a major factor in the evolution of these regions. The secondary structure of the two regions, supported by multiple compensatory base changes, is highly conserved between the species examined and supports the existence of a general folding pattern for all eukaryotes. Intriguingly, the evolutionary rate of expansion segments is very slow relative to other genic and non-genic regions of the Drosophila genome. These results suggest that the evolution of expansion segments in the rDNA multigene family is a balance between the homogenization of new mutations by unequal crossing over and a combination of selection against some such mutations per se and selection for subsequent compensatory mutations, in order to maintain a particular RNA secondary structure. PMID- 1904941 TI - Transcription activation at a distance by phage phi 29 protein p4. Effect of bent and non-bent intervening DNA sequences. AB - Protein p4 of the Bacillus subtilis phage phi 29 switches on the transcription of the viral late genes by binding to the viral late promoter at a region close to the RNA polymerase binding site. Gel retardation and DNase I footprinting assays show that the presence of protein p4 is required for RNA polymerase recognition of the late promoter. The protein p4 and RNA polymerase DNA binding sites have been separated by the insertion of bent and non-bent DNA sequences of different lengths. These mutant promoters were used to study in vitro their protein p4 dependent transcriptional activity and their interaction with both protein p4 and RNA polymerase. The results indicate that protein p4 is able to function at longer DNA distances from the RNA polymerase binding site than in the natural promoter. The extent of protein p4 activity depended on the length and conformation of the inserted DNA. Activation of transcription and RNA polymerase binding was favoured when the relative orientation of protein p4 and RNA polymerase was conserved and when the intervening DNA had a bent conformation. These data, together with the DNase I footprints, suggest that activation at distance by protein p4 involves a DNA loop held by the interaction of protein p4 and RNA polymerase. PMID- 1904943 TI - Cost-effective alternatives in alcoholism treatment revisited. PMID- 1904944 TI - Chagas disease in Ecuador: a sylvatic focus in the Amazon region. AB - A sylvatic focus of Chagas disease is reported in the Amazon region of Ecuador (provinces of Napo and Sucumbios). During 1987-1989, 10 cases of acute infection were diagnosed by direct visualization of Trypanosoma cruzi in peripheral blood smears during routine malaria checks. Also in that region, three triatomine bugs, Rhodnius pictipes, Rhodnius robustus and Panstrongylus geniculatus were found naturally infected with T. cruzi suggesting that the human cases represent an autochthonous focus of active transmission. PMID- 1904942 TI - Crystal structure of rat trypsin-S195C at -150 degrees C. Analysis of low activity of recombinant and semisynthetic thiol proteases. AB - The X-ray crystal structure of trypsin-S195C, a rat anionic trypsin mutant in which the active site serine has been replaced by cysteine, was determined at 150 degrees C and room temperature to 1.6 A resolution, R = 15.4% and 1.8 A resolution, R = 15.0%, respectively. Cryo-crystallography was employed to improve the quality of the diffraction data and the resulting structure by eliminating radiation damage and decreasing atomic thermal motion. The average temperature factor decreased by 10 A2 relative to that of the room temperature structure. No radiation-induced decay of the data was detected. The side-chains of the catalytic cysteine and histidine of trypsin-S195C are found with 25% occupancy in secondary orientations rotated 104 degrees and 90 degrees out of the active site, respectively. These alterations, as well as more subtle changes in the active site may be caused by the oxidation of the catalytic sulfur to sulfenic acid. The position of the carbonyl carbon of the tetrahedral intermediate analog, p amidinophenylpyruvic acid, modeled into trypsin-S195C, is 1.1 A from the catalytic sulfur. The large size and altered approach of the catalytic sulfur to substrates could account for the observed low catalytic activity relative to wild type trypsin. In addition to the benzamidine in the specificity pocket, two additional binding sites for benzamidine are characterized. One of these mediates an intermolecular contact that appears to maintain the crystal lattice. PMID- 1904945 TI - Long-term effects of single-dose metrifonate on the control of urinary schistosomiasis in an endemic area. AB - During 1989 a survey for urinary schistosomiasis was carried out in children attending Kanhukamwe primary school where, 5 years previously, infected children had been treated with a single dose of metrifonate. The treatment programme had been supplemented by improvements in water supply and sanitation, but no mollusciciding or other vector control measures had been used. The majority of children examined had not taken part in the treatment programme but had grown up in the community where transmission was reduced. While the prevalence of infection in the children in the current study was similar to that seen 5 years previously, the intensity of infection was markedly lower. In a nearby village where improved water and sanitation had been provided but no treatments had been given, the intensity of infection in school-children of similar age remained high. About 20% of the children originally with negative urines and so untreated had now started excreting S. haematobium ova, compared with 45% of children who had been cured following treatment. Children who had been treated in 1983 but who had continued to excrete ova were retreated in this study. It was noted that children who responded well to the previous treatment (greater than 90% reduction in egg excretion) generally responded well when retreated, while poor responders (less than 90% reduction in egg excretion on original treatment) showed only a small reduction in egg excretion on retreatment. PMID- 1904946 TI - Toward rational nutritional support of the human immunodeficiency virus-infected patient. AB - The acquired immunodeficiency syndrome and (human immunodeficiency virus) infection loom as our major public health priorities for at least the next two decades. Despite the recent exciting early development of vaccines and newer drug therapies, we are all faced with a reservoir of almost one-quarter million cases in the United States and several times that worldwide. Since the vast majority of HIV-infected patients develop AIDS, which is a chronic progressive disease that produces gastrointestinal dysfunction and wasting, development of rational strategies for nutritional support of these patients should also be a high priority. PMID- 1904947 TI - Effect of various lipid emulsions on total parenteral nutrition-induced hepatosteatosis in rats. AB - The effect of various lipid emulsions on the development of fatty liver during total parenteral nutrition (TPN) was investigated in rats given TPN for 7 days. Medium-chain triglycerides (MCT), long-chain triglycerides (LCT), chemically defined triglycerides (CDT; structured lipid with a high purity of 94.3%), and a mixture of MCT and LCT (MIX) were prepared as the lipid emulsions. TPN provided 350 kcal/kg/day, with a nonprotein calorie/nitrogen ratio of 160. The TPN-1 group received 10% nonprotein calories and the TPN-2 group received 30% nonprotein calories. MCT TPN was found to have some disadvantages, especially with regard to nitrogen balance and plasma albumin levels. Total cholesterol and phospholipids tended to be high in the MCT TPN group. The hepatic lipid content was higher in the lipid-free TPN and the MCT TPN groups, and lower in the CDT and LCT TPN groups. Histologically, the livers of the MIX, CDT, and LCT TPN groups showed less fatty change than those of the FREE and MCT groups. PMID- 1904948 TI - Estimation of nitrogen excretion based on abbreviated urinary collections in patients on continuous parenteral nutrition. AB - The physiologic response to stress can create a net loss of nitrogen, which is indicative of a catabolic state. Nitrogen balance has been demonstrated to be a useful clinical indicator of a patient's catabolic state and the effectiveness of parenteral nutrition, but requires an estimate of total urinary nitrogen excretion. The standard method for determining total urinary nitrogen excretion is 24-hour urinary urea nitrogen excretion. Unfortunately, the 24-hour urine collection is inconvenient, cumbersome, sometimes inaccurate, and induces a lag in response time to changes in therapy. Although shorter collection times have been proposed, the validity of shorter-timed determinations remains open to question. To evaluate the estimation of 24-hour urine urea excretion from shorter timed determinations, the urinary urea nitrogen excretion of 4-, 8-, and 12-hour durations was regressed against the 24-hour collection in 56 critically ill adult patients. The 12-hour determination provided satisfactory estimates of the 24 hour nitrogen excretion, but the 4-hour and 8-hour determinations did not. Thus, two times the 12-hour urine urea nitrogen determination can be substituted for the 24-hour determination in calculating nitrogen balance. A 12-hour determination can provide a more rapid turnaround of biochemical analysis, allow more timely nutritional intervention, decrease nursing time, and reduce the frequency of inaccurate or lost specimens. PMID- 1904951 TI - Implication of a distant septic focus in parenteral nutrition catheter colonization. AB - During a 4-year period, 244 surgical patients receiving total parenteral nutrition (TPN) were studied with emphasis on the relationship between TPN catheter colonization and a preexisting distant septic focus (DSF). A colonized catheter was defined as a catheter with a positive semiquantitative culture of the catheter tip (greater than or equal to 15 colonies on the plate). Catheter related sepsis (CRS) was defined as a catheter with either the same organisms cultured from the catheter tip and from blood or with defervescence following catheter removal. Two hundred sixty-nine catheters were inserted for TPN for a total of 4433 patient days, with a mean length of stay of 16.5 days. Forty-two of the 269 catheters (15.6%) were colonized and more than half (57.1%) of the organisms cultured were Gram-negative bacilli or enterococci. Nineteen of the 42 colonized catheters were associated with CRS with a CRS rate of 7.1% among the 269 catheters. A DSF was present in 165 of the 244 patients or in 188 of the 269 catheters (69.9%). The colonization rate of 19.1% (36/188) in those catheters with DSF was significantly higher than that of 7.4% (6/81) in those without DSF (p less than 0.05). Those patients with DSF or with a colonized catheter were associated with a high mortality (p less than 0.001). Sepsis was responsible for 33 of the 48 patients (68.8%) who died. The data stress the important contribution of DSF to the colonization of TPN catheters and to the mortality of these critically ill surgical patients. PMID- 1904949 TI - Effects of a fish oil diet on pigs' cardiopulmonary response to bacteremia. AB - Since an omega 3 fatty acid (FA) diet may have beneficial effects in inflammatory processes, we tested the hypothesis that the physiologic response to sepsis could be modified by altering the eicosanoid precursor pool via an omega 3 FA diet. Two groups (n = 8) of pigs were prefed for 8 days either an omega 3 FA or an omega 6 FA diet (Weaner Pig Feed with either menhaden or corn oil to produce a eucaloric feed with 15% fat) and then injected with live Escherichia coli. The omega 3 FA diet increased the concentration of eicosapentainoic acid (EPA, 20:5 omega 3) in plasma lipids, and increased the ratio of EPA to arachidonic acid (AA, 20:4 omega 6) in platelets from 1:20 to 1:1 over the 8 days. Following the injection of bacteria, there was a fall in PaO2 and blood pressure that was attenuated (p less than 0.05) by the omega 3 FA diet. The omega 3 FA diet, compared to the omega 6 FA diet, also attenuated the rise in thromboxane B2 (3.0 +/- 1.1 vs 12.9 +/- 5.7 ng/mL) and 6 keto-PGF1 alpha (0.8 +/- 0.5 vs 1.7 +/- 1.1 ng/mL) associated with bacteremia. We conclude that dietary omega 3 FA attenuated the physiologic response to sepsis, possibly by modifying arachidonic acid metabolism. PMID- 1904950 TI - Alteration of whole-body protein kinetics according to severity of surgical trauma in patients receiving total parenteral nutrition. AB - This study was conducted to clarify the mechanisms of body nitrogen losses according to the severity of surgical trauma. Thirteen male patients who underwent operation for esophageal cancer (group E), and 11 men (who underwent gastric or colorectal surgeries (group GC) were studied. The measurement of whole body protein turnover, synthesis, and breakdown were made preoperatively on the 3rd and 10th postoperative day with constant infusion of [15N]glycine during isocaloric and isonitrogenous total parenteral nutrition. Significant increases in the rates of whole-body protein turnover (flux) and breakdown were seen in group E on the 3rd postoperative day (p less than 0.01, p less than 0.01, respectively), whereas the increases were not significant in group GC. The rates of whole-body protein flux and breakdown were significantly greater in group E than group GC (p less than 0.01, p less than 0.01, respectively). The rate of protein synthesis significantly increased in group E (p less than 0.05), but did not alter or slightly decreased in group GC. The rates of whole-body protein flux and breakdown in group E were still significantly greater on the 10th postoperative day than preoperatively. It was concluded that unchanged or slightly decreased rates of whole-body protein synthesis with slightly increased breakdown were seen in the group of patients who underwent gastric or colorectal surgery, whereas synthesis increased significantly with a greater increase of breakdown in patients receiving severe surgical procedures, esophagectomy for esophageal cancer. PMID- 1904952 TI - Calcium glycerophosphate as a source of calcium and phosphorus in total parenteral nutrition solutions. AB - Calcium glycerophosphate (CaGP) was tested as an alternative to calcium gluconate (CaGluc) and potassium mono- and dibasic phosphate (KPhos) as a source of Ca and P in total parenteral nutrition (TPN) solutions for piglets. Four-day-old piglets were infused for 7 days with a TPN solution that provided either 4.2 mmol Ca and 2.1 mmol P/kg/24 h as CaGluc and KPhos (the maximum quantities that can be provided using these sources), or 15.0 mmol Ca and 15.0 mmol P/kg/24 h as CaGP. Ca and P retentions were more than six times greater (p less than 0.01) in the piglets receiving CaGP (14.5 +/- 0.2 vs 2.2 +/- 0.3 mmol Ca/kg/24 h and 13.3 +/- 0.4 vs 2.4 +/- 0.1 mmol P/kg/24 h) (Mean +/- SEM). The ratio of Ca to fat-free dry weight, an indicator of bone mineralization, was significantly higher (p less than 0.05) in the humerus (174.8 +/- 2.2 vs 147.2 +/- 6.7) and femur (158.3 +/- 4.8 vs 130.1 +/- 7.8) in the CaGP group. This study showed that CaGP is efficiently used as a source of Ca and P in TPN solutions for piglets. The results suggest that the use of CaGP as the source of Ca and P in TPN solutions may prevent the development of the undermineralized bone seen in low-birth weight infants nourished intravenously. PMID- 1904954 TI - Parenteral nutrition for marrow transplant recipients: evaluation of an increased nitrogen dose. AB - The use of total parenteral nutrition in bone marrow transplant (BMT) recipients is well recognized. These patients as a result of treatment with chemotherapy and immunosuppressive agents undergo catabolic stress. The metabolic effect of an increased nitrogen dose during total parenteral nutrition (TPN) was studied in 28 BMT patients. Patients were given TPN formulas providing a nitrogen intake of either 267 +/- 44 mg of N/kg/d or 330 +/- 60 mg of N/kg/d. Total calories, nonprotein and protein, were held constant at 40 kcal/kg/d for all patients. Data was collected for three periods posttransplant beginning at 3 days posttransplant through day 16. Both study TPN formulas improved patient weight and TIBC values over baseline. Nitrogen balance (NB) values were not significantly different at any study period. However, an overall group effect favored the H-N formula (p less than 0.01). BMT patients undergo catabolic stress which was reflected by average values of 24-hour urine urea nitrogen increasing from 8.1 +/- 4 g/d at baseline to 19.8 +/- 7.2 g/d at period 3 (p less than 0.01). The H-N formula did not differentially increase blood urea nitrogen or serum creatinine levels. Metabolic cart measures also showed no increase in metabolic rate, oxygen consumption, carbon dioxide production, or percent contribution of protein to total metabolic expenditure. Providing a caloric intake of 40 kcal/kg/d was excessive, where 30 to 35 kcal/kg/d would meet metabolic demands. Pertinent clinical outcomes including length of stay, relapse rate, and survival were monitored, but no conclusions could be drawn in this study. The H-N formula was more effective in reducing loss of lean body mass without causing detrimental metabolic effects in BMT patients. PMID- 1904953 TI - Enteral hyperalimentation with continuous subcutaneous insulin infusion improved severe diarrhea in poorly controlled diabetic patient. AB - Little is known about effective treatment for severe diarrhea in the insulin dependent diabetic patient. A 41-year-old woman was admitted to our hospital because of hyperglycemia and dysuria. She had stopped insulin self-injection therapy for 2 years and diarrhea had become worse, resulting in malnutrition. Following enteral alimentation by elemental diet (ED) with continuous subcutaneous insulin infusion (CSII), frequency of diarrhea remarkably decreased and general nutritional condition was improved. At the first step, the patient was given 600 kcal/d ED through the tube sustained in the jejunum. Total calorie intake for 24 hours was gradually increased to the level of 2400 kcal/d and this therapy continued for 5 months. During this period, blood glucose level was kept in almost normal range (between 100 and 200 mg/dL) through the continuous insulin infusion of regular insulin (1.0-1.5 U/h). Thereafter, general conditions were improved and frequency of diarrhea gradually decreased. When this treatment was stopped, watery diarrhea, steatorrhea, and hypoalbuminemia completely disappeared and she gained 12 kg of body weight. Furthermore, spontaneous urination appeared following this treatment. This case suggests that the enteral hyperalimentation combined with strict control of blood glucose, using the CSII, may be an effective therapy for such severe diarrhea with malnutrition in diabetes. PMID- 1904956 TI - [Effects of hypocapnia on hemodynamics and myocardial metabolism in anesthetized dogs]. AB - The authors previously reported that hypocapnia increased myocardial oxygen demand under droperidol-fentanyl (D-F) anesthesia. In this study, we observed myocardial oxygen tension, hemodynamics, and coronary arterial-venous blood content differences of oxygen and lactate before and after hyperventilation in dogs with and without a narrowed coronary artery under halothane anesthesia. We studied the functional and metabolic responses of the heart to hypocapnia under halothane in comparison with D-F anesthesia. In the intact heart, heart rate, LV dp/dt max and myocardial energy demand (heart rate x systolic aortic pressure x LV dp/dt max), which increased during hypocapnia under D-F anesthesia, were unchanged during hypocapnia under halothane anesthesia. Aortic pressure and coronary flow were unchanged under both types of anesthesia. Though subendocardial oxygen tension decreased significantly, myocardial lactate extraction was unchanged under both types of anesthesia. In the heart with a constricted coronary artery, subendocardial oxygen tension and lactate extraction ratio decreased significantly during hypocapnia under both types of anesthesia. Myocardial lactate production was observed in six of eleven dogs in which myocardial energy demand increased under D-F anesthesia. Myocardial lactate production was observed in one dog under halothane anesthesia. Coronary arterial venous blood oxygen content difference increased under D-F anesthesia, but not under halothane anesthesia. In summary, hypocapnia increased myocardial oxygen demand under D-F anesthesia but not under halothane anesthesia. In the intact heart under both types of anesthesia, hypocapnia deteriorated myocardial oxygen supply-demand relations, but the evidence of myocardial anaerobic metabolism was not observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1904955 TI - Parenteral drug products containing aluminum as an ingredient or a contaminant: response to Food and Drug Administration notice of intent and request for information. ASCN/A.S.P.E.N. Working Group on Standards for Aluminum Content of Parenteral Nutrition Solutions. AB - Aluminum remains a significant contaminant of total parenteral nutrition (TPN) solutions and may be elevated in bone, urine, and plasma of infants receiving TPN. Aluminum accumulation in tissues of uremic patients and adult TPN patients has been associated with low-turnover bone disease. Furthermore, aluminum has also been linked with encephalopathy and anemia in uremic patients and with hepatic cholestasis in experimental animals. Because of the toxic effects of aluminum, the Food and Drug Administration (FDA) recently published a notice of intent to set an upper limit of 25 micrograms/L for aluminum in large-volume parenterals and to require manufacturers of small-volume parenterals, such as calcium and phosphate salts, to measure aluminum content and note this content on the package label. The ASCN/A.S.P.E.N. Working Group on Standards for Aluminum Content of Parenteral Nutrition Solutions supports these intentions and further urges the FDA to require that cumulative aluminum intake in terms of safe, unsafe, and toxic quantities of aluminum per kilogram be made known to physicians and pharmacists preparing the TPN solutions, to ensure that manufacturers use appropriate control procedures in aluminum measurements, and to employ a standard unit of aluminum measurement. PMID- 1904957 TI - [Comparison of IVH and oral intake concerning the incidence of postoperative pulmonary complications (PPC)]. AB - We compared IVH with oral intake concerning the incidence of postoperative pulmonary complication (PPC), using PPC score, in which the higher the score, pulmonary function is the worse. PPC score in IVH-group was higher than that in oral-group. Although it has been suspected that, on PPC score, long term IVH group had the disorder of small airway functioning, the PPC in their group was not always high. In particular, among high score patients whose score was above 12 points in both groups, the PPC in IVH-group (30.4%) was lower than that in oral-group (60.0%). When we use PPC score, we should consider the difference in nutritional intake. PMID- 1904959 TI - [Urinary tissue-type plasminogen activator (tPA) in renal transplant patients]. AB - We have previously suggested that an appearance of FDP D-dimer fragment into the urine predicts the reversibility of acute renal transplant rejection. In the present study, we observed urinary tissue-type plasminogen activator (tPA), which is a fibrinolytic enzyme and produces D-dimer, in 51 renal transplantation patients. Urinary tPA values are generally higher in transplantation patients except on chronic rejection than in healthy controls. High values just before onset of rejection (increase of serum creatinine value), deterioration at onset phase and gradual elevation from peak phase toward recovery phase were observed in urinary tPA of 6 reversible acute rejection episodes. Urinary D-dimer values changed following urinary tPA values in serial observation of 2 cases. In conclusion, immunological reaction accompanying by functional and organic renal impediments may result in loss of fibrinolytic activity, decrease in urinary tPA and D-dimer. This findings suggest theoretically that the supplemental tPA administration prevents the progression of rejection reaction. PMID- 1904958 TI - [Thymic undifferentiated carcinoma with resection of superior vena cava: report of a case]. AB - A case of a 75-year-old woman with thymic undifferentiated carcinoma was reported. Thymic carcinoma infiltrated the right pleura, epicardium, and superior vena cava. Total thymectomy with resection of the right pleura, epicardium, and superior vena cava was performed. The superior vena cava was reconstructed with a ringed Goretex. The patient received the chemotherapy such as CDDP, VDS and MMC, and also received radiation therapy (total 5,000 rad). The postoperative clinical course was uneventful. The definition and therapy of thymic carcinoma is unclear. We think that complete resection of carcinoma is necessary even if cancer infiltrates the superior vena cava. PMID- 1904960 TI - [Therapeutic effect of ofloxacin on intractable pulmonary tuberculosis and ofloxacin resistance of tubercle bacilli isolated from the patients. Chest DIsease Cooperative Study Unit of National Sanatoriums in Kinki District]. AB - Ofloxacin, a synthetic antibacterial pyridone-carboxylic acid derivative, was used in the treatment of intractable pulmonary tuberculosis. In this study, the therapeutic effect of Ofloxacin on pulmonary tuberculosis and Ofloxacin resistance were analyzed. All patients had been hospitalized in eight national sanatoria in Kinki district, and were excreting tubercle bacilli resistant to various anti-tuberculosis drugs agents. Ofloxacin was given to 118 patients orally at a daily dose of 300 mg to 600 mg for more than 3 months. A few anti tuberculosis drugs, which had failed in the negative conversion of bacilli previously, were used in combination. By Ofloxacin, 23 patients (19.5%) showed negative conversion of tubercle bacilli in sputum culture within 5 months, and they remained culture-negative for at least 6 months after conversion. Side effects were observed in 2 patients. One complained of arthralgia and the other felt abdominal fullness. But both were not serious. From these results, it was concluded that Ofloxacin was effective for intractable pulmonary tuberculosis. The resistance of tubercle bacilli to Ofloxacin increased significantly after it was used. PMID- 1904961 TI - [Change in biochemical and biological characteristics of Mycobacterium tuberculosis strains isolated in recent years]. AB - One hundred strains of Mycobacterium tuberculosis isolated in 1988-89 from patients who were newly hospitalized in the National Chubu Hospital were studied on their biochemical and biological characteristics and compared with the strains isolated previously. Recently isolated strains showed frequently a much stronger arylsulfatase activity, grew at a higher rate at 42 degrees C, and showed a little stronger niacin production. PMID- 1904962 TI - Ultrafiltration and effective peritoneal blood flow during peritoneal dialysis in the rat. AB - The dependence between maximum net ultrafiltration rate (nUFR) created by 15% dextrose dialysis solution and effective peritoneal capillary blood flow (EPBF) estimated by the diffusive mass transport coefficient (KBD) and peritoneal clearance (Cp) of CO2 gas was evaluated during 30 minute, 15 ml peritoneal dialysis exchanges in anesthetized rats (N = 18). The values of KBD for CO2 suggested a mean EPBF of 1.9 +/- 0.1 (SEM) ml/min for isosmotic exchanges and 2.7 +/- 0.2 ml/min for hyperosmotic ones with a mean maximum nUFR of 0.43 +/- 0.01 ml/min. Cp of CO2 measured after the first five minutes of dwell underestimated EPBF. In normally hydrated rats, maximum nUFR was achieved when the peritoneal filtration fraction was 32 +/- 2%. This value is similar to the glomerular filtration fraction in rats of 30%. Thus, our results indicate the following relationships: EPBF = (approximately 3 x maximum nUFR)/(1 - hematocrit). EPBF was about six times greater than maximum nUFR and exceeded about 57 times nUFR obtained under isosmotic conditions. These differences between EPBF and nUFR suggest normal EPBF is not a major limiting factor for maximum ultrafiltration achieved during peritoneal dialysis. PMID- 1904963 TI - Inhibition of acetylcholine release from guinea pig myenteric neurons by neuropeptide Y: GTP-binding protein mediation. AB - Neuropeptide Y (NPY) is a unique peptide with wide distribution in central and peripheral nervous systems. In the guinea pig, NPY-positive fibers are prominent in the myenteric plexus. To test whether NPY inhibits myenteric plexus acetylcholine (ACh) release and to define mechanisms, a purified preparation of myenteric plexus neurons was derived from the teniae coli of neonatal guinea pigs and maintained in primary culture. Incubation of cultured neurons labeled with [3H]ACh in the presence of NPY (10(-14)-10(-6) M) significantly inhibited basal ACh release (83 +/- 16 to 58 +/- 11% of control). NPY significantly inhibited ACh release stimulated by potassium (55 mM); by adenylate cyclase agonists forskolin (10(-6) M) and cholera toxin (10(-8) M); and by calcitonin gene-related peptide, cholecystokinin octapeptide, and vasoactive intestinal peptide (each 10(-8) M). In each instance, the inhibitory effects of NPY were reversed by preincubation with pertussis toxin. Reversal of inhibitory effects by pertussis toxin suggests that the actions of NPY are mediated via an inhibitory GTP-binding protein. PMID- 1904964 TI - Change with age of UV absorbance and fluorescence of collagen and accumulation of epsilon-hexosyllysine in collagen from Wistar rats living on different food restriction regimes. AB - Accumulation of glycation products (as revealed by the thiobarbituric test and hexosyllysine assay) and the pigmented products (350 nm UV absorbance and 370ex/440em nm fluorescence) in aortal and skin collagen was investigated under the conditions of different nutritional regimes. Four groups of animals were tested: (1) ad libitum fed controls, (2) animals which were food restricted throughout their whole life (50% food intake), (3) animals fed ad libitum during their first year of life and then food restricted and (4) animals food restricted when young and fed ad libitum from the age of 1 year onwards. It was shown that all food-restricted animals showed lower levels of glycation and pigmentation products in collagen preparations from skin and aorta. The lowest accumulation was observed in group 4 which exhibited the longest 50% survival (29.4 months, as compared with 18.3 months in normally-fed controls). Of particular interest is the fact that in this group the decreased rate of accumulation of the glycated and pigmented products was preserved even after 1 year of life, i.e., when the animals had a free access to food. Though not directly supporting the glycation theory of aging (Cerami, 1985), our data are indicative of the involvement of glucose metabolism in the ageing process. Correlation between the levels of glycated and pigmented products in aortal and skin collagen as well as the correlation between the rate of accumulation of these products and 50% survival was impossible to establish. Nevertheless, each time that food restriction was imposed on the animals it always resulted in decreased accumulation of glycated and pigmented products and increased 50% survival. Possible mechanisms for this process are discussed. PMID- 1904965 TI - Hydrogen peroxide release by mitochondria increases during aging. AB - The effect of aging on the release of H2O2 by mitochondria was studied in the housefly in order to elucidate the causes of previously observed age-related increase in the level of oxidative stress. Intact flight muscle mitochondria of the housefly, supplemented with alpha-glycerophosphate, produce 1-2 nmol H2O2/min per mg protein, even in the absence of respiratory inhibitors. The rate of H2O2 secretion progressively increases approximately 2-fold during aging of the fly. Neither uncoupling of oxidative phosphorylation nor mechanical damage to mitochondria during the isolation procedure appear to be responsible for the age related increase in H2O2 production. Activities of NADH-ferricyanide reductase, succinate-ubiquinone reductase, and NADH-, succinate- and alpha-glycerophosphate cytochrome c reductases, were approximately 2-fold higher in mitochondria from the old than those from the young flies. However, the concentration of enzymatically reducible ubiquinone remained unchanged with age. Infliction of damage by exposure of mitochondria to free radical-generating systems in vitro caused an increase in the rate of H2O2 generation. Glutaraldehyde, an intermolecular crosslinking agent, induced an increase in the rate of H2O2 generation by mitochondria. Results of this study demonstrate that aging in the housefly is associated with an increase in the rate of H2O2 generation by mitochondria probably due, at least in part, to self-inflicted damage by mitochondria. Intermolecular cross-linking in the inner mitochondrial membrane can contribute towards the increased H2O2 generation. PMID- 1904966 TI - [Contrast echocardiography in the diagnosis of severe hypoxemia associated with liver cirrhosis]. AB - Severe hypoxemia is an uncommon feature of hepatic cirrhosis. Its major cause are intrapulmonary arteriovenous shunts, both due to direct arteriovenous communications and abnormally dilated pulmonary capillaries. In the present study, a case of cirrhosis associated with severe hypoxemia is reported. Contrast echocardiography showed pulmonary arteriovenous shunts, and low values of mixed venous blood (15% or less were obtained with the method of 100% oxygen breathing). These data suggest that the basic mechanism of hypoxemia, in this case, were capillary dilatations rather than true pulmonary arteriovenous anastomoses. The pathophysiological mechanisms of hypoxemia in cirrhosis are discussed, with emphasis on the present relevance of echocardiography for a full evaluation of these patients, particularly when liver transplantation is contemplated. PMID- 1904967 TI - [Bacteremic pneumonia caused by Branhamella catarrhalis in an immunocompromised patient]. PMID- 1904968 TI - Differential effects of cyclooxygenase inhibitors on the cardiovascular response to hyperosmotic mannitol. AB - The intravenous infusion of mannitol (1.37 mosm kg-1 min-1 during 4 min) to anesthetized, open-chest, intact dogs produced a hemodynamic response characterized by a positive inotropic effect and a decrease in total peripheral resistance. This response is attributable to a direct effect of hypertonicity (plasma osmolality raised from 309 +/- 4 to 332 +/- 5 mosm kg-1 H2O). Pretreatment with indomethacin (5 mg kg-1 i.v.) or meclofenamic acid (2 mg kg-1 i.v.) attenuated the mannitol-induced response but acetylsalycilic acid (10 mg kg 1 i.v.) was without effect. Indomethacin (5 mg kg-1 i.v.) did not change the decrease in canine hindlimb perfusion pressure produced by intra-arterial mannitol 5 mosm kg-1. Indomethacin (3 microM) did not alter the chronotropic and inotropic responses to mannitol (150 mosm above normal) in isolated rabbit atria. These results suggest that the cardiovascular response to hyperosmotic mannitol may be partly mediated in intact animals by prostaglandin release. PMID- 1904969 TI - Effects of oleic, arachidonic and 5,8,11,14-nonadecatetraenoic acids on lipid secretion and ketogenesis in perfused rat liver. AB - The effects of perfused oleic (18:1n-9), arachidonic (20:4n-6) and 5,8,11,14 nonadecatetraenoic (19:4n-5) acids on triglyceride and cholesterol secretion and ketone body production were studied in isolated rat liver. As compared to oleic and 19:4n-5 acids, both ketone body production and triglyceride secretion were significantly lowered when arachidonic acid was perfused. The concentration of triglyceride in the post-perfused liver was lower upon perfusion with arachidonic acid than upon perfusion with oleic acid or 19:4n-5 acid. Cholesterol secretion in the liver perfused with arachidonic acid or 19:4n-5 acid was significantly higher than with oleic acid. The concentration of cholesterol in the post perfused liver was slightly but significantly higher with 19:4n-5 acid than with the other fatty acids. The results suggest that 19:4n-5 acid when compared with arachidonic acid affects lipid metabolism in liver differently. PMID- 1904970 TI - The effects of dietary protein on the fatty acid composition and delta 6 desaturase activity of rat hepatic microsomes. AB - Recently, significant differences between rats fed a casein diet and rats fed a soybean protein diet have been observed in hepatic phospholipid fatty acid patterns (Sjoblom, L., and Eklund, A., Biochim. Biophys. Acta 1004, 187-192, 1990). The influence of these two diets on the delta 6 desaturase activity was investigated in the present study because the hepatic desaturase system is a source of unsaturated fatty acids. The rats fed a casein diet showed higher desaturase activity than those fed soybean protein when using either linoleic acid (P less than 0.005) or oleic acid (P less than 0.05) as substrates. The phosphatidylcholine fraction of hepatic microsomes showed increases in oleic acid (P less than 0.005) and 20:3 omega 9 (P less than 0.001) levels as well as decreases in stearic acid (P less than 0.001), linoleic acid (P less than 0.005) and arachidonic acid (P less than 0.005) levels in rats which were fed casein rather than soybean protein. Similar differences between the two groups were also observed in the phosphatidylethanolamine and phosphatidylinositol fractions. These data indicate that the qualitative properties of the dietary protein source may influence the fatty acid pattern of rat hepatic microsomes by interfering with delta 6 desaturase activity. PMID- 1904971 TI - Analysis of aldehydic lipid peroxidation products by TLC/densitometry. AB - We have explored the use of thin-layer chromatography (TLC)/densitometry in both the reflectance and fluorescence mode for quantitation of specific products of lipid peroxidation. Aldehydic peroxidation products were generated by exposure of arachidonic acid to iron and ascorbic acid for 24 hr. Several methods for the quantitative analysis of peroxidation products by TLC/densitometry were compared using two different aldehyde-specific derivatizing reagents, namely dinitrophenylhydrazine (DNPH) and cyclohexanedione (CHD). DNPH hydrazones of the arachidonic acid-peroxidation products, upon TLC separation on silica gel, revealed prominent alkanal and hydroxyalkenal bands. Reverse phase high performance liquid chromatography confirmed that the primary alkanal component was hexanal, while the primary hydroxyalkenal was 4-hydroxynoneal. Semiquantitative methods for the direct analysis of these products by TLC/densitometry were worked out based on the use of external hydrazone standards. TLC/densitometry (fluorescence mode) was used to measure CHD adducts of aldehydes by forming the derivatives in the presence of decanal (used as an internal standard) and separating the derivatives by reverse phase TLC. Hexanal CHD was detectable upon application of 0.5 nanomoles while 4-hydroxynoneal showed a lower response and was detectable with 10 nanomoles. Using appropriate response factors, hexanal and 4-hydroxynonenal were measured in the aldehyde sample from arachidonic acid and results were similar to those obtained by the DNPH method. Similar approaches were used to analyze the peroxidation products of docosahexaenoic acid (24-hr exposure) and of rat liver microsomes exposed to iron for 30 min. The DHA peroxidation products contained extremely low levels of alkanals, while polar aldehydes and hydroxyalkenals were prominent. Formation of alkanals, osa-zones, hydroxyalkenals and phospholipid aldehydes from iron-expoded microsomes was also demonstrated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1904972 TI - Gas chromatographic analysis of malonaldehyde and 4-hydroxy-2-(E)-nonenal produced from arachidonic acid and linoleic acid in a lipid peroxidation model system. AB - Malonaldehyde (MA) and 4-hydroxynonenal (4-HN) formed upon oxidation with Fe2+/H2O2 from arachidonic acid and linoleic acid, and their ethyl esters were analyzed by gas chromatography (GC). The MA and 4-HN produced were reacted with N methylhydrazine (NMH) to give 1-methylpyrazole and 5(1'-hydroxyhexyl)-1-methyl-2 pyrazoline, respectively. The derivatives were analyzed by GC on a fused silica capillary column using a nitrogen-phosphorus detector. With arachidonic acid, more MA and 4-HN were formed from the ester (88 nmol/mg and 23 nmol/mg, respectively) than from the free acid (25 nmol/mg and 9 nmol/mg, respectively). In contrast, with linoleic acid, more MA and 4-HN were produced from the free acid (53 nmol/mg and 13 nmol/mg, respectively) than from the ester (39 nm/mg and 8 nmol/mg, respectively). PMID- 1904974 TI - Assays for measuring arachidonic acid release from phospholipids. PMID- 1904973 TI - The effect of a salmon diet on blood clotting, platelet aggregation and fatty acids in normal adult men. AB - This study was designed to measure the effect of dietary n-3 fatty acids (FA) on platelets and blood lipids. Healthy men (n = 9), ages 31 to 65, were fed diets in which salmon was the source of n-3 fatty acids. They were confined in a nutrition suite at this Center for 100 days. Food intake and exercise levels were rigidly controlled. Initially they were placed on a stabilization diet for 20 days, then six men were fed the salmon diet for 40 days. The others remained on the stabilization diet. The two groups switched diets for the last 40 days of the study. Both diets were isocaloric [16% protein, 54% carbohydrate, and 30% fat by energy-% (En%)]. The salmon diet contained 7.5% of calories from n-6 FA and 2% from n-3 FA, primarily eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in a 40:60 ratio, while the stabilization diet contained 7.5% of calories from n 6 FA and less than 0.3% n-3 FA, mainly 18:3n-3. The bleeding time was unaffected by the diets in this study. The prothrombin time was shortened (11.6 sec. vs. 12.6 sec., p less than 0.01) for the subjects consuming the salmon diet as compared to that measured after 20 days of the stabilization diet. Mean platelet volume increased significantly during the period in which the volunteers consumed the salmon diet compared to the baseline diet (p less than 0.01), while the mean platelet levels decreased. Platelet aggregation (PA) was measured in platelet rich plasma before, during, and after the salmon diet using collagen, ADP, arachidonic acid (AA), and thrombin agonists. The PA threshold for ADP was significantly increased for the subjects on the salmon diet (p less than 0.05). No change in the PA threshold was detected for collagen or thrombin. The PA threshold for AA was unchanged also, but the platelets in subjects consuming the salmon diet had a prolonged time to maximum aggregation (p less than 0.01) with this reagent compared to platelets from men on the stabilization diet. Plasma, red cell, and platelet total FA composition was determined by capillary GLC. While the men consumed the salmon diets, there were marked increases (3 to 10 fold) in the EPA and DHA levels in all blood components with concomitant decreases in linoleic acid and AA levels.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1904975 TI - Platelet-activating factor acetylhydrolase in human erythrocytes. PMID- 1904976 TI - Assays of phospholipases on short-chain phospholipids. AB - Short-chain phospholipids are extremely useful compounds for analysis of interfacial and substrate requirements of water-soluble phospholipases. A wide variety of PCs are easily prepared and can be characterized in detail to the point where at a given PC concentration, the micelle size distribution is known, and an area per head group can be estimated. Since they can be presented to enzymes as monomers, micelles, or in bilayer structures, short-chain phospholipids are ideal for examining kinetic preferences of lipolytic enzymes. In the future detailed studies of short-chain phospholipids with different head groups should facilitate kinetics with phospholipases which show a preference for anionic substrates. PMID- 1904977 TI - Modified arteriolar responses to ATP after impairment of endothelium by light-dye techniques in vivo. AB - In this study we investigated whether endothelial cells are involved in the dilation of third-order arterioles (14 to 22 microns) in response to adenosine triphosphate (ATP) in cremaster muscle of pentobarbital-anesthetized rats. Two light/dye (L/D) techniques were employed to achieve selective, local endothelial impairment. One of these techniques utilizes a mercury lamp and sodium fluorescein, the other a Helium-Neon laser and Evans blue dye. L/D treatment (illumination with the appropriate wavelengths of light in the presence of an intravascular dye) of a 20-to 100-microns segment of an arteriole resulted in a complete loss of arteriolar dilation in response to topical administration of acetylcholine (10(-6) M) and arachidonic acid (AA, 10(-5) M). These agents were applied in 100-microl aliquots without interrupting the continuous suffusion with Ringer-gelatin solution and caused a approximately 70% increase in vascular diameter before the L/D intervention. Selectivity of the impairment was assessed by arteriolar responses to the nonendothelium-dependent dilator agents adenosine (10(-5) M) and sodium nitroprusside (2 X 10(-7) M), which elicited the same degree of dilation before and after L/D treatment. Under control conditions ATP (10(-6), 10(-5), and 10(-4) M) elicited dose-dependent increases in arteriolar diameter (from 38 to 74%). After impairment of arteriolar endothelium, dilation in response to all doses of ATP was significantly reduced. Theophylline (30 microM) significantly inhibited arteriolar dilation in response to adenosine (10( 6), 10(-5), and 10(-4) M) but did not affect the responses to various doses of ATP. Moreover, impairment of endothelium enhanced constrictor responses of arterioles to norepinephrine (0.6 X 10(-8) M). These results indicate that arteriolar endothelium of skeletal muscle can mediate or modulate arteriolar responses to various vasoactive agents, suggesting that it has an important role in the regulation of blood flow. PMID- 1904978 TI - A theoretical model of gas transport between arterioles and tissue. AB - A theoretical model of CO2 and O2 diffusion between arterioles and tissue was developed to determine if significant transport could occur in precapillary vessels. There is increasing evidence, both theoretical and experimental, that such exchange does occur. Using a model in which CO2 and O2 were coupled through the Bohr and Haldane effects, we quantified the radial and axial transport. We also examined the roles of axial diffusion in the arteriole wall and tissue and capillary structure on the transport. Capillary arrangements investigated included capillaries independent of the arteriole with the entering capillary PCO2 or PO2 equal to a constant, and capillaries branching off along the length of the arteriole with the entering capillary partial pressure equal to the arteriole partial pressure at the given axial location. We found that for CO2 in arterioles with an inner diameter ranging from 200 to 22 microns, the exiting blood was 6 to 45% of the way to complete equilibrium with the surrounding tissue, respectively. For O2, the range was 8 to 25%, respectively. We also determined that axial diffusion in the arteriole wall and tissue has little effect on the transport and that capillary structure can alter tissue PCO2 by as much as 12 mm Hg in the smallest arteriole, but has little effect on O2 transport. PMID- 1904980 TI - Activation of the c-jun protooncogene in human myeloid leukemia cells treated with etoposide. AB - The epipodophyllotoxin etoposide is an inhibitor of topoisomerase II. The effects of this agent on gene expression, particularly the transcriptional induction of genes implicated in growth control, are unknown. The present results demonstrate that etoposide induces expression of the c-jun protooncogene in HL-60 myeloid leukemia cells. This induction of c-jun expression was maximal at 3 hr and was transient. Similar findings were obtained in the human U-937 myeloid leukemia cell line. Nuclear run-on assays demonstrated that the induction of c-jun expression by etoposide is regulated at the transcriptional level. The results further demonstrate that etoposide-induced c-jun expression occurs in association with the appearance of c-fos transcripts. Moreover, the c-jun gene is induced by etoposide during periods of oligonucleosomal DNA cleavage, which is characteristic of programmed cell death. These findings suggest that transcriptional induction of c-jun expression represents a signaling pathway activated in the cellular response to etoposide-induced DNA damage. PMID- 1904979 TI - Density-dependent expression of hyaluronic acid binding to vascular cells in vitro. AB - Alterations in glycosaminoglycans and their receptors have been associated with changes in cell proliferation during development, wound healing, regeneration, and remodeling. We have previously found a differential effect of hyaluronic acid on the attachment of vascular cells in vitro; endothelial cell (EC) attachment was improved on hyaluronic acid-coated substrates, whereas that of smooth muscle cells (SMC) was reduced (Orlidge and D'Amore, 1986). To determine if hyaluronic acid binding sites are involved in these different substrate preferences, we have studied specific hyaluronic acid binding to cultured bovine aortic EC and SMC. Since very large numbers of cells are required for these binding assays (3 x 10(6)/data point), and since the level of hyaluronate binding to fixed and native SMC and EC was similar, fixed cells were used throughout this study. The effect of cell density on hyaluronic acid binding was investigated. No significant difference was observed between hyaluronic acid binding to sparse and high density SMC. On the other hand, a more than threefold elevation in specific hyaluronic acid binding was observed on low density EC when compared to binding on high density EC. Hyaluronic acid binding was found to be specific; excesses of heparan sulfate and chondroitin sulfate had no effect on the levels of specific binding. Finally, the effect of cell passage on SMC binding of hyaluronic acid was measured. Specific binding was measured from 1st to 12th passage cells and was found to increase with passage number so that by passage 12, hyaluronic acid binding was fourfold that of 1st passage cells. These data support the concept that SMC may become less differentiated upon continuous culture. Our results indicate quantitative changes in the level of hyaluronic acid binding to vascular cells as a function of their growth state. Further, these data correlate well with in vivo observations which suggest a role for hyaluronic acid in vascular development. PMID- 1904981 TI - Potent Gi-mediated inhibition of adenylyl cyclase by a phosphonate analog of monooleylphosphatidate. AB - We have previously demonstrated that monooleylphosphatidate (MOPA) and phosphatidate inhibit adenylyl cyclase in cultured fibroblasts. In this study, the specificity of the phospholipid effect was probed by analysis of the effect of phosphonate analogs of these phospholipids on adenylyl cyclase in C6 glioma cells. The MOPA phosphonate analog inhibited adenylyl cyclase, but the comparable phosphonate analog of phosphatidate was ineffective. The IC50 for inhibition of adenylyl cyclase by the MOPA phosphonate analog was similar to that of MOPA, the maximal inhibitions were comparable (approximately 45% inhibition of hormone stimulated adenylyl cyclase), and the effects of both appeared to be mediated by Gi, because treatment with islet-activating protein reduced the inhibition to 5 10%. PMID- 1904982 TI - Role of Ca2+ ion on Leishmania-macrophage attachment. AB - Leishmania donovani, the etiological agent for the disease visceral leishmaniasis, attach themselves to the macrophages for initiation of the disease. The attachment process has been found to be regulated by Ca2+ ions. Verapamil, a Ca(2+)-channel blocker inhibits Leishmania-macrophage attachment. The inhibitory effect is increased with time. Nifedipine, another Ca(2+)-channel blocker exhibits the same effect. The attachment process is stimulated by Ca(2+) ionophore alone. The inhibitory effects of the calcium channel blockers are reversed by the ionophore. PMID- 1904983 TI - Role of protein phosphorylation and inositol phospholipid turnover in rat parotid gland proliferation. AB - The involvement of protein phosphorylation in isoproterenol (ISO)-mediated proliferation in the rat parotid gland was investigated by labeling the cells with [32P] orthophosphate. An increased (4-6 fold) incorporation of the radiolabel was noted in the total parotid gland homogenates of ISO-treated animals when compared to controls. Plasma membrane, nuclear membrane and cytoplasm were isolated, the proteins separated by SDS/PAGE and the phosphoproteins detected by autoradiography. Two phosphoproteins with apparent Mr of 45 and 170 kDa were identified in the cytoplasm while the 170 kDa phosphoprotein also appeared as part of plasma membrane. Transfer of these proteins to nitrocellulose followed by Western blot detection with an antiphosphotyrosine monoclonal antibody showed reactivity with the 170 kDa region of the plasma membrane and cytoplasm. Separate in vitro studies involving incubations of rat parotid slices with 0.2 mM ISO and [3H] myo-inositol for 1 min induced inositol phosphate hydrolysis resulting in a significant increase in inositol-bis and -tris phosphate production. Inositol phosphate production can be blocked by pre-incubation with a mixed beta-adrenergic receptor antagonist but not with physiological concentrations of alpha- or beta 1-specific adrenergic receptor antagonists, indicating the ISO effects are mediated through the beta 2 adrenergic receptors. The inclusion of calmodulin antagonists along with ISO prevented the expression of cell-surface galactosyltransferase and retarded gland hypertrophy and hyperplasia. These results suggest that ISO treatment leads to the phosphorylation of target proteins which may be involved in signal transduction pathways leading to cell proliferation. PMID- 1904984 TI - Simulation study of the effects of multiple treatments in the mouse bone marrow micronucleus test. AB - The effect of multiple treatment with chemicals in the micronucleus test was evaluated by simulation involving an estimation of the additive accumulation of micronucleated polychromatic erythrocytes (MNPCEs) on the basis of time-response data available on single treatments with mitomycin C, 1-beta-D arabinofuranosylcytosine, 6-mercaptopurine, and methotrexate. The frequency of MNPCEs calculated for different multiple treatment regimens by the model could predict the effects observed in real experiments. On the other hand, the effect of multiple treatments on bone marrow depression, expressed as a decrease in the frequency of polychromatic erythrocytes, was exponential according to both the simulation and actual data. These results suggest that although increasing the number of treatments may additively enhance the MNPCE response obtained with some agents it may, in the case of bone marrow-toxic chemicals and doses, make micronucleus analysis more time-consuming and even impossible due to the exponential decrease of analyzable cells, especially in the case of manual scoring. PMID- 1904985 TI - The mode of action of 1-beta-D-arabinofuranosylcytosine in inhibiting DNA repair; new evidence using a sensitive assay for repair DNA synthesis and ligation in permeable cells. AB - Mammalian cells permeabilised by treatment with saponin are capable of UV excision repair. We have developed an assay system which permits measurement of the later stages of repair, i.e. repair synthesis and ligation. Incomplete repair sites are accumulated in UV-irradiated cells by incubating them with DNA synthesis inhibitors hydroxyurea and aphidicolin. On removal of the inhibitors at the time of permeabilisation, these incomplete sites, detected as DNA breaks, are rapidly ligated in a reaction that requires deoxyribonucleoside triphosphates and is blocked by aphidicolin. Thus ligation is possible only after a significant amount of DNA synthesis. We have used the assay to clarify the mode of inhibition of DNA repair by 1-beta-D-arabinofuranosylcytosine (ara C), another DNA polymerase inhibitor. It is well known that incomplete repair sites accumulated in whole cells with ara C are ligated at a slow rate, if at all. The hypothesis that ara C blocks or reduces further polymerisation after its incorporation into repair patches is disproved by our demonstration that, in permeable cells, the accumulated DNA breaks are ligated very rapidly. The likely explanation of the action of ara C is that, once phosphorylated, it remains in the cell as ara CTP and continues to inhibit polymerisation through competition with dCTP; in permeable cells, it readily leaks out. PMID- 1904986 TI - Plasmodium falciparum-infected erythrocytes contain an adenylate cyclase with properties which differ from those of the host enzyme. AB - It has been postulated that differentiation of the human malaria parasite, Plasmodium falciparum, is controlled by cAMP levels. We have determined that P. falciparum synthesizes an adenylate cyclase with several properties distinct from those of the mammalian host cell enzyme. Adenylate cyclase activity was compared in P. falciparum-infected erythrocytes, isolated parasites free of host cell material, and uninfected erythrocyte membranes. The parasite enzyme was unaffected by GTP gamma S, AlF4-, and forskolin, while the erythrocyte enzyme was markedly stimulated by each of these compounds. The parasite adenylate cyclase also exhibited a striking preference for Mn2+ over Mg2+, which was not evident in the erythrocyte enzyme. Moreover, differing cation and pH sensitivities were observed for adenylate cyclase activity in the two cell types. When infected and uninfected erythrocytes were compared, the basal adenylate cyclase activity of infected cells was 7 and 49 times that measured in uninfected erythrocytes in the presence of Mg2+ and Mn2+, respectively. Furthermore, adenylate cyclase activity in infected cells exhibited properties typical of the parasite enzyme. This indicates that synthesis of the parasite enzyme rather than stimulation of the host enzyme accounts for the increased activity in infected cells. PMID- 1904987 TI - Ribosomal RNA sequences of Sarcocystis muris, Theileria annulata and Crypthecodinium cohnii reveal evolutionary relationships among apicomplexans, dinoflagellates, and ciliates. AB - Sarcocystis muris is a coccidium with a two-host life cycle involving the domestic cat and the mouse, Mus musculus. S. muris and Theileria annulata belong to the phylum Apicomplexa, but the latter organism is a tick-borne protozoon in the subclass Piroplasmea and causes tropical theileriosis in cattle. The small subunit ribosomal RNA (16S-like rRNA) coding regions of these organisms as well as that of the free living dinoflagellate Crypthecodinium cohnii were amplified using polymerase chain reaction techniques and compared to 16S-like rRNA sequences from other eukaryotes. The 16S-like rRNA genes of S. muris and T. annulata are more similar to each other than either is to Plasmodium falciparum, the cause of malignant tertian malaria of humans or Plasmodium berghei, the agent of the commonly studied malaria of rodents. Evolutionary trees inferred from the rRNA sequence similarities support a close phylogenetic relationship between the Apicomplexa and Dinoflagellata as represented by Prorocentrum micans and C. cohnii. Apparently members of these related phyla arose from an ancestral stock that gave rise to the ciliated protozoa. PMID- 1904988 TI - Alterations in Krebs cycle enzyme activities and carbohydrate catabolism in two strains of Trypanosoma brucei during in vitro differentiation of their bloodstream to procyclic stages. AB - A rapid switch from a fermentative to a primarily oxidative type of glucose utilization was observed during in vitro differentiation of Trypanosoma brucei STIB348 and EATRO1244 bloodstream to procyclic trypomastigotes. In accordance with previously published reports bloodstream populations produced pyruvate as the major end product of glucose catabolism, together with very small amounts of CO2, succinate and glycerol. During differentiation pyruvate excretion decreased within 48 h to the low levels produced by 28-day procyclic stages. Concomitant with the decline in pyruvate formation, acetate appeared as a new product and the rates of respiratory CO2 increased considerably. The amount of carbon released with these compounds could account for nearly all of the glucose carbon consumed. Rates of glucose utilization and formation of acetate and CO2 in cells differentiated for 48 h were essentially the same as those found in 28-day procyclics. Succinate and glycerol excretion remained low during the entire transformation process, and no significant difference in the pattern and quantities of end products were found between the two trypanosome strains. During trypanosome differentiation the changes in metabolism were associated with marked alterations in enzyme activity levels. Activities of the tricarboxylic acid (TCA) cycle enzymes citrate synthase, isocitrate dehydrogenase (NAD+), succinate dehydrogenase and fumarase were not detectable in bloodstream trypomastigotes but appeared upon differentiation for 24 h. An exception was citrate synthase whose activity was not demonstrable until 48 h postinoculation into culture. After 48 h the majority of the TCA cycle enzyme activities continued to increase steadily until day 28. Pyruvate kinase activity decreased in differentiating cells after 48 h to about 25% of the level found in bloodstream trypomastigotes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1904989 TI - Cost effectiveness of prophylactic intravenous immune globulin in chronic lymphocytic leukemia. AB - BACKGROUND: A recent randomized controlled trial of intravenous immune globulin in patients with chronic lymphocytic leukemia and hypogammaglobulinemia demonstrated a statistically significant reduction in the rate of bacterial infections among patients who received intravenous immune globulin. We used decision-analysis techniques to determine whether prophylactic intravenous immune globulin is likely to result in an overall clinical benefit to patients who receive this treatment and to examine its cost effectiveness. METHODS: We constructed a model to compare two strategies: treatment with intravenous immune globulin at a dose of 400 mg per kilogram of body weight every three weeks and no immune globulin therapy. Baseline estimates of the efficacy of intravenous immune globulin were derived from the published results of the randomized trial. The costs of treatment, complications, and infections were estimated on the basis of component costs. Health outcomes were measured in terms of gains in quality adjusted life expectancy. RESULTS: Intravenous immune globulin therapy can result in a loss of quality-adjusted life expectancy when the inconvenience of treatment is taken into account. If the inconvenience of treatment is not considered, therapy results in a gain of 0.8 quality-adjusted days per patient per year of therapy at a cost of $6 million per quality-adjusted life-year gained. CONCLUSIONS: Decision-analysis modeling may be applied to the results of randomized controlled trials to assess the potential clinical and financial effects of adopting the intervention in medical practice. In the case of intravenous immune globulin therapy in patients with chronic lymphocytic leukemia and hypogammaglobulinemia, this type of analysis suggests that treatment might not result in improved quality or length of life and that it is extraordinarily expensive in comparison with other treatments generally accepted as cost effective. PMID- 1904990 TI - Cost effectiveness of child health programs. PMID- 1904991 TI - Growth characteristics of enterococci isolated from Laban Rayeb. AB - Eleven strains of Enterococcus (Streptococcus) faecalis isolated from Laban Rayeb, a type of fermented milk, had been studied when grew in milk. Enterococcus (Streptococcus) faecalis strains 19 and 22 were the most active strains in the production of lactic acid, acetaldehyde and diacetyl. Both strains exhibited a high proteolytic activity besides a good clean flavour. Based on the obtained results, Enterococcus (Streptococcus) faecalis 19 and 22 could be used to bring about the lactic fermentation during the manufacture of some cultured dairy products. PMID- 1904992 TI - Analysis of choroideraemia gene. PMID- 1904993 TI - Adaptive protein evolution at the Adh locus in Drosophila. AB - Proteins often differ in amino-acid sequence across species. This difference has evolved by the accumulation of neutral mutations by random drift, the fixation of adaptive mutations by selection, or a mixture of the two. Here we propose a simple statistical test of the neutral protein evolution hypothesis based on a comparison of the number of amino-acid replacement substitutions to synonymous substitutions in the coding region of a locus. If the observed substitutions are neutral, the ratio of replacement to synonymous fixed differences between species should be the same as the ratio of replacement to synonymous polymorphisms within species. DNA sequence data on the Adh locus (encoding alcohol dehydrogenase, EC 1.1.1.1) in three species in the Drosophila melanogaster species subgroup do not fit this expectation; instead, there are more fixed replacement differences between species than expected. We suggest that these excess replacement substitutions result from adaptive fixation of selectively advantageous mutations. PMID- 1904994 TI - [Increase in the number of gonorrhea cases with increased antibiotic resistance in Amsterdam]. PMID- 1904995 TI - The concentration of glial fibrillary acidic protein increases with age in the mouse and rat brain. AB - The role of aging in the expression of the astrocyte protein, glial fibrillary acidic protein (GFAP), was examined. In both mice and rats the concentration of GFAP increased throughout the brain as a function of aging. The largest increase (2-fold) was observed in striatum for both species. The neuron-specific proteins, synapsin I and neurofilament-200 (Mr 200 kilodaltons), were not altered by aging in any region of the mouse or rat brain. Brains of aged rats, but not mice, showed a decrease in beta-tubulin. The data suggest that astrocytic hypertrophy observed with aging involves an accumulation of glial filaments. PMID- 1904996 TI - Phorbol ester receptors in cerebral cortex of cats with GM1 gangliosidosis. AB - The pathogenesis of neuronal dysfunction in the gangliosidoses is poorly understood. Studies of the feline gangliosidoses and in vitro experiments implicate ganglioside inhibition of protein kinase C (PKC) in the pathogenesis of these neurological diseases. Therefore, in the present study, the binding of [3H]phorbol-12, 13 dibutyrate was measured to determine the levels of PKC in cerebral cortex of cats with GM1 gangliosidosis (mutant) and age matched normal siblings. This binding of ([3H]PDB) to cerebral cortex homogenates in both normal and mutant cats was highly specific. The specificity of receptors was ascertained also from displacement studies using nonradioactive phorbol ester analogues to displace [3H]PDB bound to its receptors. In both mutant and normal cat brain, phorbol 12,13-dibutyrate (PDB), 4-beta-phorbol 12,13-didecanoate (beta-PDD) and 4 beta-phorbol 12,13-dibenzoate (beta-PDBz) were highly potent (approximately to same degree) and effective in displacing [3H]PDB. On the other hand, 4-beta phorbol 12,13-diacetate (beta-PDA) was a weak displacer and 4-alpha-phorbol did not displace the bound [3H]PDB in either normal or mutant brain. Scatchard analysis of the binding data indicated a homogenous single class of binding sites in normal and mutant brain (Normal: Kd = 1.42 x 10(-7) M, Bmax = 8.40 pmoles/mg protein. Mutant: Kd = 1.60 x 10(-7) M, Bmax = 10.00 pmoles/mg protein). Sphingosine inhibited the binding to approximately the same extent in normal and mutant cortex. These studies demonstrate the presence of highly specific, homogenous, single type phorbol ester receptors in cerebral cortex of cats with GM1 gangliosidosis which are qualitatively and quantitatively similar to normal cat brain. PMID- 1904997 TI - Correlation of functional recovery after a 6-hydroxydopamine lesion with survival of grafted fetal neurons and release of dopamine in the striatum of the rat. AB - Female rats were lesioned with 6-hydroxydopamine in the left substantia nigra. At least two weeks later they were tested with amphetamine (5 mg/kg, s.c.) and apomorphine (0.25 mg/kg, s.c.). A cell suspension from the ventral mesencephalon of rat embryos was distributed in three sites in a triangular fashion in the center of the denervated striatum. The amphetamine test was then repeated every month for six months. The pattern of circling to amphetamine before the graft was strictly ipsiversive in all animals. From the first month we observed a progressive change and three patterns of rotation could be observed. In 21% of animals, the total number of ipsiversive turns in 90 min actually increased but during the first 20 min the animals turned contralaterally to the lesion (and to the graft). In 38% of animals, the total number of turns switched from ipsiversive to contraversive with the animals turning initially toward the intact side and during the second half of the test toward the lesion. Finally 41% of rats progressively switched to turning only toward the intact side. In all cases, maximal contraversive turning occurred during the initial 20 min. In these rats, tyrosine hydroxylase-positive cells were detected mainly in the dorsal striatum with a few in the central portion. Moreover there was a strong correlation between the number of surviving grafted neurons and the growth of their fiber into the host striatum and the extent of recovery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1904998 TI - A model for carbamate and organophosphate-induced emesis in humans. AB - In human volunteers, studies to assess the adverse effects of the carbamate anticholinesterase physostigmine showed that the intramuscular dose observed to induce emesis in 50% of subjects tested (ED50) was 28.1 (23.5-120.7) micrograms/kg. This dose reduced whole blood cholinesterase (ChE) activity to 60% of control values. Studies in marmosets to assess the behavioural toxicology of physostigmine showed that the corresponding ED50 and ChE activity values were 34.3 (21.5-55.8) micrograms/kg and 66% respectively. Sarin was also shown to induce emesis in marmosets, but only at doses that reduced erythrocyte ChE activity to 12% of control values. These data seem also to correspond with reports of organophosphate poisoning in humans. It is concluded that the marmoset may be a very good model of both carbamate and organophosphate-induced emesis in humans. PMID- 1904999 TI - Home parenteral nutrition at Auckland Hospital. AB - This paper reports the results of home parenteral nutrition (HPN) from Auckland Hospital. In the last two and a half years, six patients have gone home from hospital on HPN. Four are still on it, after periods of from one to 30 months. There has been one death and one patient who developed catheter sepsis. Quality of life on HPN has in general been very good. Body composition studies performed on these patients have shown that a normal body composition can be maintained while on HPN. PMID- 1905000 TI - The antibiotic sensitivity patterns of Bacillus anthracis isolated from the Kruger National Park. AB - Forty-four isolates of Bacillus anthracis made from carcasses and soil in different localities of an endemic anthrax area in the Kruger National Park, South Africa, were tested by standard disc diffusion for their susceptibility to 18 different antibiotics. These were ampicillin, penicillin G, sulphatriad, streptomycin, clindamycin, gentamicin, fusidic acid, trimethoprim, sulphamethoxazole, chloramphenicol, erythromycin, methicillin, tetracycline (2 different concentrations), novobiocin, cefotaxime, netilmicin, cefamandole and cefoxitin. All the isolates were susceptible to ampicillin, streptomycin, chloramphenicol, erythromycin, tetracycline, methicillin and netilmicin. More than 90% of the isolates were sensitive to clindamycin, gentamicin and cefoxitin, whereas only 84.1% of the isolates were sensitive to penicillin G, 86.4% to novobiocin and 68.18% to cefamandole. Complete resistance in 100% of the isolates was encountered with trimethoprim and sulphamethoxazole, with 95.45% for sulphatriad. Moderate sensitivity occurred with penicillin G (15.9% of the isolates), clindamycin (6.8%), novobiocin (13.6%), fusidic acid (84.1%), cefotaxime (100%), cefamandole (31.8%) and cefoxitin (6.8%). The relevance of the findings to the therapeutic uses of different types of antibiotic in human clinical cases referred to in the literature is discussed. PMID- 1905001 TI - The biochemical, morphological and virulence profiles of Bacillus anthracis isolated in the Kruger National Park. AB - The biochemical, morphological and virulence profiles of 44 Bacillus anthracis isolates, obtained from various localities and carcass remains of wild animals in the Kruger National Park, South Africa, were examined. The morphological characteristics tested for included: the formation of capsules on bicarbonate agar, the motility of the vegetative organism, the presence of haemolysis on blood tryptose agar, the sensitivity of the vegetative organism to bacteriophage, the production of lecithinase on egg yolk agar, the liquefaction (hydrolysis) of gelatine and the capability of each isolate to produce mucoid colonies when grown on bicarbonate agar with horse serum in an atmosphere containing CO2. The API 50CHB and 20E systems were used to evaluate the biochemical activity of each isolate. The virulence of each isolate was determined by its LD50, using an inbred line of Balb/C mice. A clear pattern in the biochemical reactions emerged that appeared to be specific for each isolate. On the API 50CHB test strip, only 2 of the 44 isolates gave a 100% positive reaction to all 10 of the biochemical substances to which it was supposed to react, 9 gave positive results to 90%, 19 were positive to 80%, and 14 were positive to 70%. The reactions on the API 20E were completely different from what was expected, with only 1 of the biochemical activities (gelatinase production) showing a positive reaction to all the isolates. The virulence test indicated that 27/44 isolates could be regarded as highly virulent with a LD50 of less than 1,000 organisms, and the rest of the isolates as virulent with a LD 50 of 1,001-10,000 organisms.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1905003 TI - Oral manifestations of radiation therapy in infancy. PMID- 1905002 TI - Reproductive parameters in free-ranging female black rhinoceroses (Diceros bicornis) in Zimbabwe. AB - Samples and data were collected from twenty-eight female black rhinoceroses (Diceros bicornis) during translocation efforts carried out by the Department of National Parks and Wildlife Management in Zimbabwe. Biological data were collected, cytological examination of vaginal smears was performed, and serum concentrations of follicle stimulating hormone, luteinizing hormone, progesterone, oestriol, and 17-beta-oestradiol were determined by radio-immuno assay. Prolactin levels were determined for 3 pregnant animals, 1 of which was sampled before and after parturition. Vaginal cytology was not found to be helpful for indicating the oestrous cycle stage for the black rhinoceros, but progesterone and 17-beta-oestradiol levels were found to be useful indicators of pregnancy and possibly of oestrous cycle stage as well. PMID- 1905004 TI - The lck tyrosine protein kinase. PMID- 1905005 TI - Human Harvey-ras is biochemically different from Kirsten- or N-ras. AB - The biochemical effects of the human H-, N- and K-ras oncogenes were studied. We analysed the induction of c-fos mRNA and protein by the protein kinase C (PKC) activator 12-O-tetradecanoyl-phorbol-13-acetate (TPA) in exponentially growing NIH3T3 fibroblasts transformed by transfection with ras oncogenes. We found that H-ras has the unique ability to inhibit c-fos induction by TPA. In contrast, normal c-fos expression was induced by TPA in fibroblasts transformed by N- or K ras or by the ras-unrelated oncogenes dbl and trk. The inhibition of c-fos induction by H-ras was not due to alteration in the binding of TPA to the transformed cells or to the selection of idiosyncratic clones. These results provide clear evidence that H-ras is functionally different from K- or N-ras. PMID- 1905007 TI - [Determination of factors promoting, in vitro, the expression of adhesion of Pseudomonas aeruginosa to buccal cells]. AB - The composition of the bacterial flora in the upper respiratory tract is closely correlated with the type of pathogens recovered from the respiratory tract in patients. In intensive care patients, colonization of the oral cavity with Gram negative organisms increases the risk of Gram-negative respiratory tract infection; the ability of bacterial cells to attach to buccal cells seems to play a central role in this correlation. Similar findings have been reported in chronic respiratory tract infections, including bronchiectasis and cystic fibrosis, with Pseudomonas aeruginosa colonization. This study was undertaken to determine the conditions best suited to in vitro detection of adhesion of P. aeruginosa to buccal cells. Use of brain-heart-infusion medium, incubation at 35 degrees C for 2 hours, and a bacterial concentration of 2 x 10(9) cells/ml were the factors correlated with improved detection of adhesion to buccal cells. Furthermore, attachment of bacteria to buccal cells was not found to vary across donors or over time in a given donor. Adhesion was independent of cell viability. PMID- 1905006 TI - The murine rac1 gene: cDNA cloning, tissue distribution and regulated expression of rac1 mRNA by disassembly of actin microfilaments. AB - A 886 bp cDNA encoding the murine rac1 protein has been isolated. The abundance of rac1 mRNA was determined in fourteen tissues from both mouse and pig. The mRNA 5' non-coding sequence is very rich in G + C, and has the potential to form several stable secondary structures. In addition, this region contains a putative open reading frame of 57 amino acids. Disruption of the actin microfilament network by cytochalasin B in LLC-PK1 cells results in down regulation of rac1 mRNA. In agreement with the proposed role of rac1 in exocytosis, these results could explain the inhibitory effect of cytochalasin B on secretory processes. PMID- 1905008 TI - [Value and limitations of anti-mannan antibodies research by co immunoelectrodiffusion in the diagnosis of deep candidiasis]. AB - Several groups have evaluated detection of antibodies against Candida, with somewhat conflicting results. In this study, co-counterimmunoelectrodiffusion was used to detect antimannan antibodies specific of components of the Candida membrane. Study patients were divided into two groups according to whether their history for Candida infection was negative (population A, n = 102) or positive (population B). Different antigen levels were used in order to differentiate low and high antimannan antibody levels. Among the 102 sera in population A, 42 were positive for antimannan antibodies; the antimannan antibody titer was low in 40 cases and high in 2 cases. In population B (53 patients), antimannan antibodies were found in 97 of the 98 sera studied; titers were high in 95 cases. Use of an antigen level that detects only high titers of antimannan antibodies thus provides a sensitive and specific tool for the diagnosis of deep candidiasis. The simplicity and rapidity of this test are particularly valuable in situations where emergency treatment is needed. PMID- 1905009 TI - Quantitative analysis of the active tablet ingredient by powder X-ray diffractometry. AB - A powder X-ray diffraction technique has been developed for the quantitative analysis of the active ingredient in intact tablets. Two model drugs were used: lithium carbonate (LC) and carbamazepine (CBZ). Mixtures containing various weight fractions of each drug and microcrystalline cellulose were compressed into tablets and the integrated intensities of several diffraction lines of each were used for quantitative purposes. The ratio of the integrated intensity of these lines in tablets, made from mixtures of drug and microcrystalline cellulose, to the intensity of the same lines in tablets made from only drug was calculated as a function of the weight fraction of the drug in the mixture. These ratios were also experimentally determined and the relative error in the determination of LC was less than 12%. CBZ tablets containing starch were also prepared. In the CBZ tablets containing microcrystalline cellulose or starch, the relative error in the determination of CBZ was less than 10% only when the weight fraction of CBZ in the tablets was greater than or equal to 0.4. PMID- 1905010 TI - Photosynthetic electron transport controls nitrogen assimilation in cyanobacteria by means of posttranslational modification of the glnB gene product. AB - A glnB gene is identified in the cyanobacterium Synechococcus sp. PCC 7942, and its gene product is found to be covalently modified as a result of imbalance in electron transfer in photosynthesis, where photosystem II is favored over photosystem I. The gene was cloned and sequenced and found to encode a polypeptide of 112 amino acid residues, whose sequence shows a high degree of similarity to the Escherichia coli regulatory protein, PII. In E. coli, PII is involved in signal transduction in transcriptional and post-translational regulation of nitrogen assimilation. Increase in ammonium ion concentration is shown to decrease covalent modification of the Synechococcus PII protein, as in enteric bacteria. We therefore propose that the photosynthetic electron transport chain may regulate the pathway of nitrogen assimilation in cyanobacteria by means of posttranslational, covalent modification of the glnB gene product. The existence of the glnB gene in different strains of cyanobacteria is demonstrated and its implications are discussed. PMID- 1905011 TI - Long-term in vivo expression of retrovirus-mediated gene transfer in mouse fibroblast implants. AB - Toward the goal of gene therapy, we have been attempting to establish model somatic cell systems with the potential of sustained expression of the foreign gene. We report here that long-term expression of foreign genes in mouse embryo fibroblast implants can be achieved if a housekeeping gene promoter is used to drive transcription. Specifically, we have shown that in implants containing a beta-galactosidase gene linked to either an immediate early promoter of cytomegalovirus or a dihydrofolate reductase (DHFR) gene promoter, only the DHFR promoter allows long-term expression. We propose that choice of the promoter manifests significant influence on the long-term expression of genes introduced in fibroblast implants by retroviral vectors. PMID- 1905012 TI - Serodiagnosis of hepatitis C virus (HCV) infection with an HCV core protein molecularly expressed by a recombinant baculovirus. AB - An enzyme-linked immunosorbent assay (ELISA) was developed for serological diagnosis of hepatitis C virus (HCV) infection, using HCV core protein (p22) synthesized by a recombinant baculovirus. Among 58 clinically well-defined chronic non-A, non-B hepatitis (NANBH) patients, 49 (84.5%) were positive for p22 antibody (anti-p22), whereas 42 (72.4%) were positive for C100-3 antibody (anti C100-3), as measured by the present assay using the HCV nonstructural protein as antigen. Thirty-nine patients (67.2%) had both antibodies. No significant level of anti-p22 was detected in sera of chronic hepatitis B patients or normal blood donors. In typical post-transfusion NANBH patients, anti-p22 could be detected at, or even before, the first alanine aminotransferase peak. Anti-p22 was also detected in blood donors who were previously shown to be involved in transmitting HCV but in whose serum anti-C100-3 was not detectable. The ELISA detecting antibody to the HCV core protein expressed and properly processed in animal cells will be useful for mass screening of donor blood as well as for early diagnosis of hepatitis C. PMID- 1905013 TI - Muscarinic acetylcholine receptor subtypes as agonist-dependent oncogenes. AB - We have evaluated the muscarinic acetylcholine family of G protein-coupled receptors (mAChRs) for their oncogenic potential. These receptors are preferentially expressed in postmitotic cells, transducing signals specified by their endogenous agonist, the neurotransmitter acetylcholine. Cells transfected with individual human mAChR genes were morphologically indistinguishable from parental NIH 3T3 cells in the absence of agonist. In contrast, when cultures were supplemented with carbachol, a stable analog of acetylcholine, foci of transformation readily appeared in m1, m3, or m5 but not in m2 or m4 mAChRs transfectants. Receptor expression was verified by ligand binding and was similar for each transfected culture. Transformation was dose-dependent and required only low levels of receptor expression. In transformation-competent cells, agonist induced phosphatidylinositol hydrolysis, whereas in m2 or m4 transfectants, receptors were coupled to the inhibition of adenylyl cyclase. These findings demonstrate that mAChRs linked to phosphatidylinositol hydrolysis can act as conditional oncogenes when expressed in cells capable of proliferation. PMID- 1905015 TI - Bispecific antibodies that mediate killing of cells infected with human immunodeficiency virus of any strain. AB - Although AIDS patients lose human immunodeficiency virus (HIV)-specific cytotoxic T cells, their remaining CD8-positive T lymphocytes maintain cytotoxic function. To exploit this fact we have constructed bispecific antibodies that direct cytotoxic T lymphocytes of any specificity to cells that express gp120 of HIV. These bispecific antibodies comprise one heavy/light chain pair from an antibody to CD3, linked to a heavy chain whose variable region has been replaced with sequences from CD4 plus a second light chain. CD3 is part of the antigen receptor on T cells and is responsible for signal transduction. In the presence of these bispecific antibodies, T cells of irrelevant specificity effectively lyse HIV infected cells in vitro. PMID- 1905014 TI - Immunogenicity of an engineered internal image antibody. AB - We engineered an antibody expressing in the third complementarity-determining region of its heavy chain variable region a "foreign" epitope, the repetitive tetrapeptide Asn-Ala-Asn-Pro (NANP) of the circumsporozoite protein of Plasmodium falciparum parasite, one of the etiologic agents of malaria in humans. A monoclonal antibody to P. falciparum specific for the (NANP)n amino acid sequence bound to the engineered antibody, and a synthetic (NANP)3 peptide blocked this interaction. Immunization of rabbits and mice with the engineered antibody resulted in the elicitation of a humoral response to (NANP)3 synthetic peptide and P. falciparum parasite. In mice, in which immunity to the (NANP)n epitope is highly restricted by immune response genes, antibodies were induced in responder and nonresponder haplotypes of the major histocompatibility complex. Rabbit antibodies efficiently inhibited the in vitro invasion of cultured liver cells by P. falciparum parasite. Collectively, this study indicates that immunity to malaria in the absence of the parasite can be induced using antibody variable regions engineered to mimic the parasite's molecular structure. In general terms, the results suggest that antibody (idiotype) mimicry of an exogenous antigen is possible and may only require a discrete stretch of identity between the two molecules. The implication for the preparation of antibody-based vaccines and idiotype regulation of immunity are discussed. PMID- 1905016 TI - Mutation in a reporter gene depends on proximity to and transcription of immunoglobulin variable transgenes. AB - Somatic mutation in immunoglobulin genes is localized to a 2-kilobase region of DNA surrounding and including rearranged variable (V), diversity, and joining (J) gene segments encoding heavy and light chains. To examine the structural basis for targeted mutation, we developed an assay to score mutation on plasmid substrates by using a reporter gene: a bacterial gene encoding an amber suppressor tRNA molecule was placed 3' of a rearranged kappa VJ gene within the boundaries of mutation. The reporter gene is exquisitely suited for mutational analysis because it is only 200 base pairs (bp), which should not greatly disrupt structure of the immunoglobulin locus, and gene function depends on secondary structure, which means mutation can be scored in many different nucleotide positions. The plasmid was used to make transgenic mice, which were then immunized. The shuttle vector was retrieved by plasmid rescue into an indicator strain of Escherichia coli that contained an amber mutation in its beta galactosidase gene. Integrity of the tRNA molecule was monitored by colony color, which permitted many transformants to be screened visually. Mutations were not seen in DNA from a transfected B-cell line grown in vitro or in DNA from nonlymphoid tissue of transgenic mice, indicating that the reporter gene was stable during cell division and DNA manipulations. However, when the transgenic mice were immunized, DNA from splenic B cells contained point mutations in the reporter gene at a frequency of 10(-3) per transformant. Sequence analysis of 17 mutated transgenes revealed that the mutations were 1- and 2-bp deletions in the tRNA gene, and one plasmid had an additional 2-bp deletion in the V gene. In contrast, previous studies have shown that mutations in endogenous VJ genes are predominantly nucleotide substitutions and have only 6% deletions. Two other plasmid constructs were analyzed in transgenic lines: no mutations were found when the tRNA gene was placed distal to the VJ gene, and no mutations were seen when the immunoglobulin promoter was deleted. Although we lack direct evidence that the deletions in the tRNA gene are caused by the same mechanism that acts on VJ genes, we have shown that mutations in this assay occur in a manner consistent with immunoglobulin-specific mutation in that they are found in splenic B cells and not in tail tissue, depend on position next to the VJ gene, and require transcription of the VJ gene. PMID- 1905017 TI - An alternative spliced form of FosB is a negative regulator of transcriptional activation and transformation by Fos proteins. AB - Two forms of FosB transcript and their products can be identified in mouse NIH 3T3 cells following serum induction. The larger RNA codes for a 338-amino acid protein, whereas the smaller RNA results from the removal of an additional 140 nucleotides from FosB mRNA by alternative splicing. This alternative splicing event places a stop codon following the "leucine zipper" region and results in a shorter protein (FosB2) of 237 amino acids that lacks 101 amino acids at the carboxyl terminus. FosB2 is able to form heterodimers with c-Jun and bind to an AP-1 site but is not able to activate the transcription of promoters containing AP-1 sites. Furthermore, FosB2 can not only suppress the transcriptional activation by c-Fos and c-Jun of promoters containing an AP-1 site but also interferes with the transforming potential of viral and cellular Fos proteins. We propose that FosB2 protein functions as a trans-negative regulator. PMID- 1905018 TI - Synergistic action of diacylglycerol and unsaturated fatty acid for protein kinase C activation: its possible implications. AB - Kinetic properties of the purified alpha, beta, and gamma subspecies of protein kinase C (PKC) to respond to diacylglycerol, phosphatidylserine (PtdSer), and Ca2+ were reinvestigated in the presence of several fatty acids. Although responses of these enzyme subspecies to the lipids slightly differed from one another, the reaction velocity of these subspecies was significantly enhanced by synergistic action of diacylglycerol and a cis-unsaturated fatty acid. Arachidonic, oleic, linoleic, linolenic, and docosahexaenoic acids were active in this role, whereas saturated fatty acids such as palmitic and stearic acids were inactive. Elaidic acid was also inactive. In the presence of both PtdSer and diacylglycerol, the cis-unsaturated fatty acids increased further an apparent affinity of PKC to Ca2+ and allowed the enzyme to exhibit almost full activation at nearly basal levels of Ca2+ concentration. The concentration of fatty acid giving rise to the maximum activation of enzyme was approximately 20-50 microM. The result presented herein implies that the receptor-mediated release of unsaturated fatty acids from phospholipids may take part, in synergy with diacylglycerol, in the activation of PKC even when the Ca2+ concentration is low. A possibility arises, then, that the activation of PKC is an integral part of the signal-induced degradation cascade of various membrane phospholipids, which is initiated by the actions of phospholipase C and phospholipase A2. PMID- 1905019 TI - Suppression of c-Jun/AP-1 activation by an inhibitor of tumor promotion in mouse fibroblast cells. AB - Curcumin, a dietary pigment responsible for the yellow color of curry, is a potent inhibitor of tumor promotion by phorbol esters. Functional activation of transcriptional factor c-Jun/AP-1 is believed to play an important role in signal transduction of phorbol 12-myristate 13-acetate-induced tumor promotion. Suppression of the c-Jun/AP-1 activation by curcumin is observed in mouse fibroblast cells. In vitro experiments indicate that inhibition of c-Jun/AP-1 binding to its cognate motif by curcumin may be responsible for the inhibition of c-Jun/AP-1-mediated gene expression. These findings show that the effect of curcumin on phorbol 12-myristate 13-acetate-induced inflammation/tumor promotion could be studied at the molecular level. PMID- 1905020 TI - Monomeric and trimeric forms of photosystem I reaction center of Mastigocladus laminosus: crystallization and preliminary characterization. AB - Photosystem I (PSI) reaction centers (RCs) of the thermophilic cyanobacterium Mastigocladus laminosus were purified and characterized. The PSI RC was obtained in two forms, monomeric and trimeric. The two forms contained the same number of pigments per P700 and displayed similar photochemical activities. The two forms had nearly identical polypeptide subunit compositions; the only observed difference was an additional subunit of about 12 kDa observed in the trimeric form. The purified preparations of both the monomeric and the trimeric forms were used for crystallization and preliminary crystallographic analysis. The trimeric PSI RC preparations produced several three-dimensional crystal forms, one of which, the "hexagonal needle" form (THN), had a hexagonal unit cell with dimensions of 300 x 300 x 160 A, containing four PSI RC trimers. The monomeric preparations also produced single crystals of several forms under various crystallization conditions. One of these crystal forms, the "hexagonal plate" (MHP), diffracted to a resolution of about 5.5 A. It had a hexagonal unit cell with dimensions of 192 x 192 x 163 A, containing six PSI RC monomers. Comparison of the PSI RCs in the crystals with those in the precrystallization preparations demonstrated that neither the monomeric nor the trimeric form of PSI RC was altered by the crystallization process. Both forms retained their original polypeptide subunit composition and their pigment content. PMID- 1905021 TI - Involucrin gene of tarsioids and other primates: alternatives in evolution of the segment of repeats. AB - The involucrin genes of the prosimian primates and of the anthropoid primates possess nonhomologous segments of repeats located at two different sites, P and M, within the coding region. The involucrin gene of the tarsioids alone contains repeats at both sites, for it derived repeats at site P from a common ancestor of tarsioids and prosimians and a repeat at site M from a later common ancestor of tarsioids and anthropoids. After their divergence from the tarsioids, the anthropoids added many more repeats to site M and excised the older segment of repeats from site P; in contrast, the tarsioids stopped adding repeats at site M, retained the earlier segment of repeats at site P, and enlarged it. In the revision of their involucrin genes, the two lineages followed alternative routes. The mechanisms by which the revisions took place have been subject to abrupt onset or termination. PMID- 1905022 TI - acj6: a gene affecting olfactory physiology and behavior in Drosophila. AB - Mutations affecting olfactory behavior provide material for use in molecular studies of olfaction in Drosophila melanogaster. Using the electroantennogram (EAG), a measure of antennal physiology, we have found an adult antennal defect in the olfactory behavioral mutant abnormal chemosensory jump 6 (acj6). The acj6 EAG defect was mapped to a single locus and the same mutation was found to be responsible for both reduction in EAG amplitude and diminished behavioral response, as if reduced antennal responsiveness to odorant is responsible for abnormal chemosensory behavior in the mutant. acj6 larval olfactory behavior is also abnormal; the mutation seems to alter cellular processes necessary for olfaction at both developmental stages. The acj6 mutation exhibits specificity in that visual system function appears normal in larvae and adults. These experiments provide evidence that the acj6 gene encodes a product required for olfactory signal transduction. PMID- 1905023 TI - Prostaglandin and thromboxane biosynthesis. AB - We describe the enzymological regulation of the formation of prostaglandin (PG) D2, PGE2, PGF2 alpha, 9 alpha, 11 beta-PGF2, PGI2 (prostacyclin), and thromboxane (Tx) A2 from arachidonic acid. We discuss the three major steps in prostanoid formation: (a) arachidonate mobilization from monophosphatidylinositol involving phospholipase C, diglyceride lipase, and monoglyceride lipase and from phosphatidylcholine involving phospholipase A2; (b) formation of prostaglandin endoperoxides (PGG2 and PGH2) catalyzed by the cyclooxygenase and peroxidase activities of PGH synthase; and (c) synthesis of PGD2, PGE2, PGF2 alpha, 9 alpha, 11 beta-PGF2, PGI2, and TxA2 from PGH2. We also include information on the roles of aspirin and other nonsteroidal anti-inflammatory drugs, dexamethasone and other anti-inflammatory steroids, platelet-derived growth factor (PDGF), and interleukin-1 in prostaglandin metabolism. PMID- 1905024 TI - The prevention of minority youth violence must begin despite risks and imperfect understanding. PMID- 1905025 TI - Forum on youth violence in minority communities. Violence is a greater killer of children than disease. PMID- 1905026 TI - Forum on youth violence in minority communities. Charge to the participants: from analysis to action. PMID- 1905027 TI - Forum on youth violence in minority communities. The Kansas City project. PMID- 1905028 TI - Forum on youth violence in minority communities. Boston's violence prevention project. PMID- 1905029 TI - Forum on youth violence in minority communities. The coalition for alternatives to violence and abuse. PMID- 1905030 TI - Forum on youth violence in minority communities. New way of fighting. PMID- 1905031 TI - Forum on youth violence in minority communities. Alternatives to gang membership: the Paramount Plan. PMID- 1905032 TI - Forum on youth violence in minority communities. Focusing public attention on violence prevention. PMID- 1905033 TI - Forum on youth violence in minority communities. Establishing a public-private partnership. PMID- 1905034 TI - Forum on youth violence in minority communities. The federal role in a public private partnership. PMID- 1905035 TI - Forum on youth violence in minority communities. Application of principles of community intervention. PMID- 1905036 TI - Violence prevention strategies targeted at the general population of minority youth. PMID- 1905037 TI - Violence prevention strategies directed toward high-risk minority youths. PMID- 1905038 TI - Weapons and minority youth violence. PMID- 1905039 TI - Forum on youth violence in minority communities. Interventions in early childhood. PMID- 1905040 TI - Forum on youth violence in minority communities. Needed: a new pathway to the prevention of violence. PMID- 1905041 TI - Forum on youth violence in minority communities. Prevention of violence: a public health commitment. PMID- 1905042 TI - Forum on youth violence in minority communities. The prevention of violence--a top HHS priority. PMID- 1905043 TI - Forum on youth violence in minority communities. Application of the principles of community-based programs. PMID- 1905044 TI - Violence prevention strategies targeted at the general population of minority youth. PMID- 1905045 TI - Violence prevention strategies targeted towards high-risk minority youth. PMID- 1905046 TI - Weapons and minority youth violence. PMID- 1905047 TI - Forum on youth violence in minority communities. Interventions in early childhood. PMID- 1905048 TI - Forum on youth violence in minority communities. Evaluation of community-based violence prevention programs. PMID- 1905050 TI - A national survey of state maternal and newborn drug testing and reporting policies. AB - The prevalence rate of drug use by pregnant women in the United States has been shown to range from 7.5 percent to 11 percent. Drug exposure in utero has been associated with deleterious effects on the fetus and newborn. Public health officials are currently confronted with difficult policy decisions with regard to testing and reporting of pregnant and post-partum women and the provision of appropriate services. The widespread lack of consistent policy on the State level has led to bias in testing and reporting procedures and to the inappropriate use of the legal system as a deterrent to drug use during pregnancy. A survey of the 50 States and the District of Columbia found that no State currently has enacted legislation regarding testing. Thirteen States have mandatory reporting policies for drug-exposed newborns. Eleven of these States require reporting to social service agencies, at least 3 States routinely report to criminal justice agencies, and 10 require that reports be filed as child abuse or neglect. Many States without mandatory reporting statutes indicate that reports are made to social service agencies at the discretion of the health care provider. During fiscal year 1990, only 22 States specifically allocated funds for programs that address perinatal substance use. In States with mandatory reporting policies, reports should be made only to social service agencies in conjunction with the provision of appropriate preventive, medical, and social services to the woman and her infant. Interagency coordination is necessary to standardize testing and reporting practices within States and to effectively allocate resources. PMID- 1905049 TI - Estimates of economic costs of alcohol and drug abuse and mental illness, 1985 and 1988. AB - The high prevalence of alcohol and drug abuse and mental illness imposes a substantial financial burden on those affected and on society. The authors present estimates of the economic costs from these causes for 1985 and 1988, based on current and reliable data available from national surveys and the use of new costing methodology. The total losses to the economy related to alcohol and drug abuse and mental illness for 1988 are estimated at $273.3 billion. The estimate includes $85.8 billion for alcohol abuse, $58.3 billion for drug abuse, and $129.3 billion for mental illness. The total estimated costs for 1985, $218.1 billion, include $51.4 billion for direct treatment and support costs; $80.8 billion for morbidity costs, the value of reduced or lost productivity; $35.8 billion for mortality costs, the value of foregone future productivity for the 140,593 premature deaths associated with these disorders, based on a 6 percent discount rate and including an imputed value for housekeeping services; and $47.5 billion in other related costs, including the costs of crime, motor vehicle crashes, fire destruction, and the value of productivity losses for victims of crime, incarceration, crime careers, and caregiver services. The cost of acquired immunodeficiency syndrome associated with drug abuse is estimated at $1 billion, and the cost of fetal alcohol syndrome is estimated at $1.6 billion. The estimates may be considered lower limits of the true costs to society of alcohol and drug abuse and mental illness in the United States. PMID- 1905051 TI - Building skills of recovering women drug users to reduce heterosexual AIDS transmission. AB - Although most women infected with HIV are intravenous drug users, some contact the virus through sexual contact with IV drug users. To reach at-risk women, public health officials must develop a range of prevention strategies. One approach, skills training, holds promise as a means of altering risk-related sexual behavior. In this study, 91 women methadone patients were pretested and randomly assigned to an information-only control control group or a skills building intervention group. Skills-building intervention consisted of five sessions of small groups in which participants identified their own high risk sexual behaviors, discussed their negative associations with condoms, and practiced skills which involved asking partners to use condoms. Compared with members of the control group, respondents in the intervention group reported that they initiated discussion of sexual issues with their partners more frequently, felt more comfortable talking with them about safer sex, and reported using and carrying condoms more frequently. The high rates of attendance and program retention by skills-building participants suggest that such groups may be supportive and useful in the design of risk reduction and drug abuse treatment programs. The modest outcomes of this study underscore the difficulty of altering risk behavior but also serve as a basis for future AIDS prevention studies. PMID- 1905052 TI - Promoting heart health for Southeast Asians: a database for planning interventions. AB - This paper is a report of baseline data that the authors collected on the prevalence of hypertension in a sample of 397 Southeast Asian immigrants residing in central Ohio and the implications of those data for the design of ethnically approved and scientifically valid interventions. The context for collection of these data over a 9-month period in 1989 is described. Baseline demographic characteristics including distributions by ethnicity, sex, age, and length of stay in the United States, as well as family heart health history, hypertension level, and heart health awareness of these subjects are presented. For example, 85 percent of the immigrants did not know what could be done to prevent heart disease. Implications for the design of ethnically approved and scientifically valid prevention strategies are discussed. Based on these data, the authors realized that multiple health education strategies tailored to what they were learning about Southeast Asians would be needed. Through Southeast Asian leaders, they were led to using wall calendars, with words specific to each Southeast Asian language, that had a monthly heart health slogan as one avenue to reach Southeast Asians. Another strategy was to develop videotapes featuring cultural content but including heart health "commercials." The authors concluded that, although scientific validity of risk reduction interventions are important, customizing these strategies to ethnically specific modes of interaction are equally important. PMID- 1905053 TI - Current status of health promotion activities in four midwest cities. AB - Community-wide surveys were conducted in Winona and St. Cloud, MN, Eau Claire, WI, and Sioux Falls, SD, in 1986 and 1987 to determine the current status of the supply and demand of health promotion activities in nine categories. Supply and demand indicators were conceptualized and defined as program options (different activities in a coded list) and participation (registrations). An annual inventory of all health promotion activities in each community was complied from interviews with providers of such activities. Interviews of probable community providers was followed by a nomination process to identify others. Providers at worksites were interviewed in a separate study with matching data endpoints. Results show that exercise programs have the highest levels of options and participation in all four cities. On the supply side of total programs offered, there was similarity in rates among three of the cities, with only Winona offering more health promotion opportunities. There was similarity also in the areas of health where most programs are offered, favoring exercise, followed by the heart disease risk factor areas of screening, smoking cessation, and nutrition education. On the demand side of participation, there was similarity in total participation rates among three of the four cities with Sioux Falls showing substantially higher demand. Exercise showed the highest participation in all cities, but there was little similarity among the cities in ranking participation in the other areas of health promotion. In the four cities combined, high levels of program options with low participation were characteristic of smoking cessation. In contrast, low levels of program options and high participation were shown in chemical dependency. Worksites are the main providers of health promotion programs for adults, with schools and colleges also major program providers. Educational organizations account for the largest percentage of total participation in health promotion. PMID- 1905054 TI - Shigellosis from swimming in a park pond in Michigan. AB - In July 1989 an outbreak of shigellosis occurred among visitors to a recreational park in Oakland County, MI. An epidemiologic investigation discovered an association between illness and swimming in a pond at the park, especially for those who had put their head underwater. No other factors were epidemiologically incriminated. A total of 65 cases were identified; nine were culture confirmed, all Shigella sonnei. Several water samples evaluated for fecal coliform counts shortly after the outbreak were found satisfactory. Cultures of water samples were negative for Shigella species. Inspection of the park's sewage disposal and toilet facilities found all equipment in proper working condition and no evidence of a sewage contamination event from these potential sources. No other commercial or residential sources of potential sewage contamination existed near the pond. Investigators concluded that Shigella contamination of the pond by a swimmer or swimmers on one or more occasions was a strong possibility. Factors supporting this conclusion included elevated incidence of S. sonnei in the community during the 2 months prior to the outbreak, greater use of the pond, warm water and air temperatures, and inadequate water exchange in the pond. This report adds one of the few documented outbreaks of shigellosis implicating bather contamination to the literature on the growing number of incidents that have been associated with recreational use of water. PMID- 1905055 TI - Dientamoeba fragilis detection methods and prevalence: a survey of state public health laboratories. AB - Dientamoeba fragilis is a pathogenic protozoan parasite that has no cyst stage. Because of the lack of a cyst stage, the laboratory detection of D. fragilis in stool specimens is dependent on the stool processing and examination methods employed. Failure to use recommended stool fixation and permanent staining techniques almost precludes identification of D. fragilis, which is associated with gastrointestinal illness in humans. In this survey, questionnaires were mailed to all State and territorial public health laboratories requesting information on the number of ova and parasite examinations, methods of processing and examining stools, and the number of D. fragilis positive stools for 1985. Forty-three of 54 (80 percent) laboratories responded. Results showed that those laboratories which reported D. fragilis detection examined more stools using recommended stool fixation methods and were more likely to stain permanently all stools examined. Permanent staining of all stools, as compared to loose and watery stools only, resulted in a fivefold greater detection of D. fragilis. More State and territorial public health laboratories reported finding D. fragilis infections in 1985 than in a 1978 survey performed by the Centers for Disease Control. However, in 1985 only six laboratories reported 82 percent of all D. fragilis detections. To increase the probability of detecting D. fragilis in stool specimens, the findings suggest that all stools should be submitted fixed in polyvinyl alcohol fixative, sodium acetate-acetic acid-formalin fixative, or Schaudinn's fixative. Further, all specimens, regardless of consistency, should be permanently stained prior to microscopic examination. PMID- 1905056 TI - Quantifying the disease impact of cigarette smoking with SAMMEC II software. AB - Smoking-Attributable Mortality, Morbidity, and Economic Costs Software, Release II (SAMMEC II) has been developed for the Office on Smoking and Health, Public Health Service, to permit rapid calculation of deaths, years of potential life lost, direct health-care costs, indirect mortality costs, and disability costs associated with cigarette smoking. For the mortality-related measures, age specific and age-adjusted rates are also calculated. The pivotal epidemiologic measure in these calculations is the smoking-attributable fraction, and attributal risk measure. A multiple-measure approach (attributable mortality and economic costs) to quantifying a health problem is termed "disease impact estimation." Previously, national and State-specific estimates of smoking attributable mortality and economic costs were calculated using SAMMEC software, the predecessor of SAMMEC II. SAMMEC II is completely menu-driven and operates within the Lotus 1-2-3 software as a set of linked spreadsheets. SAMMEC II adapts national epidemiologic methods for use by State and local health departments. Increased exposure of public health professionals to disease impact estimation techniques, as demonstrated by SAMMEC II, will lead to improvements in both methodology and the quality of smoking-related health data. The primary purpose of SAMMEC II, however, is to provide State or locality-specific data on the health consequences of smoking to policymakers and public health professionals in these jurisdictions. PMID- 1905057 TI - Problems in estimating the number of women in need of subsidized prenatal care. AB - For effective allocation of resources, public program planners need to know how many women require subsidized prenatal care and where they are located. Because sample surveys are expensive, indirect methods of estimation using secondary data sources are frequently used to arrive at quick annual estimates. Census data on poverty are often incorporated into such methods, but out study of the eight southeast States in Federal Region IV shows that available census data severely underestimate the proportion of pregnant women who are poor. Updated poverty data from the 1990 census will not solve this problem of underestimation. Alternative methods for estimating the number of women in need of subsidized prenatal care services, for measuring unmet need, and for doing estimates on the county level are presented and evaluated. Such considerations are especially important, given the new Title V block grant reporting requirements. PMID- 1905058 TI - New York State's two-dose schedule for measles immunization. AB - In April 1989, New York became the first State in the United States to adopt a two-dose schedule for routine measles immunization. Although a two-dose schedule had been under discussion for the previous 10 years, this policy change was finally prompted in New York State by widespread measles outbreaks in 1989 among college and high school students who had been appropriately vaccinated with a single dose of measles vaccine. These outbreaks affected 21 college and secondary school campuses with 91 cases of measles and led to the administration of 53,093 doses of vaccine at a cost in excess of $859,000 for vaccine alone. In addition, there were major disruptions of intercollegiate athletic and scholastic events and physician and public confusion over the different recommendations for "outbreak" versus "routine" measles immunization. In response, the New York State Department of Health adopted a policy of two doses of measles vaccine required for entrance into kindergarten and college beginning in the fall of 1990. This report describes the data and process that were used in reaching this policy decision. PMID- 1905059 TI - Effects of intravenous and aerosolized arachidonic acid on alveolar epithelial permeability in rabbits. AB - To determine whether arachidonic acid (AA) alters alveolar epithelial permeability, we studied the effect of both continuous intravenous and aerosolized AA on clearance of [99m]Tc-DTPA from lung to blood in rabbits. Although intravenous AA increased prostacyclin production and aerosolized AA decreased systemic blood pressure, neither continuous intravenous nor aerosolized AA augmented alveolar epithelial permeability. PMID- 1905061 TI - [The prevention of ectopic ossification in total hip endoprostheses. Studies on field volume, total dosage and timing of postoperative radiotherapy]. PMID- 1905060 TI - Crossover comparison of maximum dose glyburide and glipizide. AB - Patients with non-insulin-dependent diabetes mellitus (NIDDM) failing to respond to therapy with a maximum dose of glyburide (GB) or glipizide (GZ) are often given a trial of the alternate second-generation sulfonylurea (SGS) before insulin therapy is considered. The efficacy of this therapeutic maneuver has not been thoroughly tested. We studied 26 subjects with fasting serum glucose (FSG) levels greater than 8.3 mmol/L (150 mg/dL) despite maximum doses of either GB (20 mg/day) or GZ (40 mg/day). Group 1 consisted of 16 subjects taking GB (mean FSG = 12.7 mmol/L [228 mg/dL]) and group 2 included 10 subjects taking GZ (mean FSG = 13.0 mmol/L [234 mg/dL]). Subjects continued taking their original SGS for 8 weeks then switched to a maximum dose of the alternate agent for an additional 8 weeks. Values for FSG, hemoglobin A1c, and lipids were recorded before the study and after 8 weeks on each SGS trial. No significant changes were noted for any variable in either group. When maximum dose GB therapy was compared to maximum dose GZ therapy in the combined study group (n = 26), no advantage was noted for either agent. We conclude that metabolic control in NIDDM patients failing to respond to therapy with maximum dose GB or GZ is not improved by switching to the alternate SGS. PMID- 1905062 TI - Prostate carcinoma--the value of T stage and grade in predicting metastases and prognosis. A cost-effective approach to clinical staging. AB - In order to evaluate the initial T stage and tumour grade as predictors of metastatic disease and prognosis in adenocarcinoma of the prostate, 963 patients were reviewed. Of the patients, 41% presented with metastatic disease. Stage T4 tumours were associated with a consistently poor prognosis, and 70% of such patients had demonstrable distant metastases. No patient with TOf local disease had metastases or died of prostate cancer during follow-up. The incidence of metastases was also low in stages T1 and T2. High tumour grade correlated strongly with more advanced disease. Using this information a more cost-effective approach to the staging of prostate carcinoma is proposed. PMID- 1905063 TI - The lumbar mamillo-accessory foramen: a study of 203 lumbosacral spines. AB - We have examined 203 lumbar and sacral skeletal specimens and have noted the frequent occurrence of a mamillo-accessory foramen, formed by the ossification of the mamillo-accessory ligament. The dorsal ramus of the lumbar nerve passes through this foramen. At the L5 level, this foramen is found frequently: in 26% of the cases on the left side and in 13.5% on the right. In some cases it is seen as a simple, deep notch. It is found much less frequently at L4 and almost never seen above. It is equally rare at the sacral level where it is formed by a narrowing and closure of the groove between the zygapophyseal joint and the sacral lateral mass. The authors propose that these bony foramina are a manifestation of osteoarthritic changes and that they could, in certain cases, irritate or compress the dorsal ramus along its passage. PMID- 1905064 TI - Immunohistochemical localization of tissue-type plasminogen activator in the lining wall of chronic subdural hematoma. AB - Capsules of chronic subdural hematoma were immunohistochemically stained with monoclonal antibody against tissue-type plasminogen activator. Endothelial cells of sinusoids and capillaries in the outer membrane showed strong immunostaining. Endothelial cells of veins and arteries in the dura mater showed moderate and weak staining. No cells other than the endothelial cells were stained. In the inner membrane, tissue-type plasminogen activator immunoreactivity was not seen. The mean concentration of tissue-type plasminogen activator in the hematoma content was higher than that in the plasma. The more the sinusoids in the outer membrane were developed, the higher the concentration of tissue-type plasminogen activator contained in the hematoma fluid. In chronic subdural hematoma, overproduction and oversecretion of tissue-type plasminogen activator from the sinusoidal and capillary endothelial cells in the outer membrane cause increased fibrinolysis, which in turn impairs hemostasis, and hemorrhage from the capillaries recurs, resulting in enlargement of the chronic subdural hematoma. PMID- 1905065 TI - [Bonding of crown fragments with dentin bonding agents and porcelain veneers]. AB - Measurements of fracture strengths of incisors from sheep, previously fractured and then restored by reattaching the fragments with a light-curable resin, revealed that pretreatment of the fracture surfaces with dentin bonding agents such as Gluma, Tenure or Scotchbond2 and acid-etching of the enamel, gave values of about half the fracture strength of intact teeth. Measurements furthermore demonstrated that pretreatment by a combination of dentin bonding agents and acid etching of the enamel yielded higher fracture strengths of the restored teeth, than that of teeth restored using only one of the two pretreatments. Fractured incisors, restored by Gluma-treatment of the dentin, acid-etching of the enamel and fragment-bonding with a light-curable resin, were further restored with porcelain veneers after preparation. Fracture strength measurements of such restored teeth revealed strength not significantly different from that of intact teeth. It is suggested that such restorations, could have a reasonably long period of function clinically. PMID- 1905067 TI - Thromboembolism and bleeding tendency in congenital factor XII deficiency--a study on 74 subjects from 14 Swiss families. AB - In order to assess the clinical implications of hereditary F XII deficiency, all available members of Swiss families with F XII deficiency were investigated. Based on the F XII:C values and the family pedigree, the 74 subjects, aged 8-82 years, were classified as homozygotes/double heterozygotes for F XII deficiency (n = 18), as obligatory (n = 20) or possibly (n = 25) heterozygotes, respectively, and as normals (n = 11). None of the 18 subjects with F XII:C less than 0.01 U/ml and only one possibly heterozygous woman had an abnormal bleeding tendency, confirming the notion that Hageman trait generally does not result in a hemorrhagic diathesis. Two of the 18 subjects with severe F XII deficiency had suffered from venous thromboembolic disease at age less than 40 years. One heterozygous woman had a leg ulcer probably due to venous thrombosis. Thus, whereas homozygous F XII deficiency may be associated with an increased risk for venous thromboembolic disease, partial F XII deficiency is not, by itself, a strong risk factor for thrombosis. Whereas 17 of the 18 subjects with F XII:C less than 0.01 U/ml had no detectable F XII:Ag, one cross reacting material positive F XII deficient subject (F XII:Ag = 0.11 U/ml) was identified. The dysfunctional F XII, present in this subject's plasma and tentatively called F XII Bern, is the fourth abnormal F XII molecule identified so far. PMID- 1905066 TI - [Possible interaction between theophylline and fluvoxamine]. PMID- 1905068 TI - The acute effect of insulin on tissue plasminogen activator and plasminogen activator inhibitor in man. AB - The present study was performed to elucidate the acute effect of insulin on levels of tissue plasminogen activator (t-PA) and plasminogen activator inhibitor of endothelial cell type (PAI-1). Nine middle-aged, non-obese and non-smoking men were studied during a hyperinsulinemic, euglycemic glucose clamp for 2 h. Plasma insulin level during the clamp averaged 84 +/- 12 mU/l and euglycemia was maintained at 4.9 +/- 0.6 mmol/l. The t-PA activity gradually increased (75% mean increase after 2 h, p less than 0.001) and the PAI-1 activity decreased (49% mean decrease after 2 h, p less than 0.001) during the clamp. t-PA activity decreased and PAI-1 activity increased after the insulin infusion was ceased, but they were still 48% higher and 38% lower, respectively, after 60 min. PAI-1 and t-PA activities were not affected by saline infusion for 2 h. Thus, acute changes in the insulin levels lead to rapid alterations in the fibrinolytic system even when euglycemia is maintained. These effects may be induced by insulin itself or by the concomitant activation of the sympatho-adrenal system during the euglycemic clamp. PMID- 1905069 TI - An analysis of the activators of single-chain urokinase-type plasminogen activator (scu-PA) in the dextran sulphate euglobulin fraction of normal plasma and of plasmas deficient in factor XII and prekallikrein. AB - An analysis was made of the various possible activators of single-chain urokinase type plasminogen activator (scu-PA) in the dextran sulphate euglobulin fraction (DEF) of human plasma. scu-PA activators were detected in an assay system in which the substrate scu-PA, in physiological concentration (50 pM), was immuno immobilized. After activation of the immobilized scu-PA for a certain period of time the activity of the generated amount of immuno-immobilized two-chain u-PA was determined with plasminogen and the chromogenic substrate S-2251. The scu-PA activator activity (scuPA-AA) in the DEF of plasmas deficient in factor XII or prekallikrein was about half of that in the DEF of normal plasma. Separation of scuPA-AA in the DEF by gel chromatography showed to major peaks, one eluting with an apparent Mr of 500,000 and the other around Mr 100,000. The former peak, which coincided with the activity peak of the kallikrein-kininogen complex, was absent in the DEF of plasma depleted of prekallikrein and therefore was identified as kallikrein. The latter peak was still present in the depleted plasma and most likely represents plasmin, because its scuPA-AA coincided with the activity peak of plasmin and could be fully inhibited by antibodies raised against human plasminogen. It is concluded that plasmin and the contact-activation factor kallikrein each contribute for about 50% to the scuPA-AA in the DEF. Compared on a molar basis, however, plasmin was found to be almost 1,000 times more effective than kallikrein, and we conclude, therefore, that in vivo plasmin is the primary activator of scu-PA and the role of the contact system is of secondary importance. PMID- 1905070 TI - Thrombolytic and pharmacokinetic properties of human tissue-type plasminogen activator variants, obtained by deletion and/or duplication of structural/functional domains, in a hamster pulmonary embolism model. AB - A pulmonary embolism model in hamsters was used for the quantitative evaluation of the thrombolytic and pharmacokinetic properties of variants of tissue-type plasminogen activator (t-PA). A 25 microliters 125I-fibrin labeled human plasma clot was made in vitro and injected into the jugular vein of heparinized hamsters. The extent of thrombolysis within 90 min was determined as the difference between the radioactivity injected in the jugular vein and that recovered in the heart and lungs. Recombinant t-PA (home-made rt-PA or Activase) infused intravenously over 60 min caused dose-dependent progressive thrombolysis. The results of thrombolytic potency (clot lysis in percent versus dose administered in mg/kg) and of specific thrombolytic activity (clot lysis in percent versus steady state plasma level in microgram/ml) were fitted with an exponentially transformed sigmoidal function y = 100 c/(1 + e-a(ax-eh] and the maximal percent lysis (c), the dose or plasma level at which maximal rate of lysis is achieved (b) and the maximal rate of lysis (z = 1/4 ac.eb) were determined. With rt-PA, these parameters were c = 72 +/- 6% (mean +/- SEM), b = 0.19 +/- 0.08 mg/kg, z = 68 +/- 25% lysis per mg/kg, with corresponding values of 87 +/- 5%, 0.07 +/- 0.03 mg/kg and 150 +/- 38% lysis per mg/kg for Activase (p = NS). Deletion of the finger and growth factor domains in rt-PA (rt-PA-delta FE) was not associated with marked alteration of the thrombolytic potency (c = 90 +/- 30%, b = 0.34 +/- 0.35 mg/kg, and z = 54 +/- 14% per mg/kg), but was associated with a significant reduction of the specific thrombolytic activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1905071 TI - Subcellular distribution and phosphorylation of vinculin isoforms in human blood platelets. AB - In this study we investigated human blood platelet vinculin microheterogeneity, the subcellular localization and phosphorylation of the different isoforms before and after platelet stimulation. At least 5 vinculin isoforms could be detected, as well as meta-vinculin. These isoforms did not demonstrate a specific subcellular localization, i.e. their relative content was similar in cytoskeleton, membrane skeleton and cytosol. Upon platelet stimulation with thrombin a small increase in alpha-vinculin was noted in all platelet subfractions. The cytoskeleton of non-stimulated platelets contained a minor quantity of vinculin. Upon thrombin stimulation of the platelets the cytoskeletal vinculin content increased significantly; previously we already reported a maximal 10% incorporation of the total platelet vinculin content into the cytoskeleton upon stimulation. A phosphorylation of a minor vinculin-isoform, i.e. at the alpha'/alpha location was mainly detected in the cytoskeleton. This phosphorylation was observable in the non-stimulated platelet cytoskeletal vinculin. These findings argue against a regulatory role for vinculin phosphorylation in the uptake of the main isoforms of this protein in the platelet cytoskeleton upon thrombin stimulation. The function of the phosphorylated cytoskeletal vinculin remains to be established. PMID- 1905072 TI - Archaeal rRNA operons. AB - Ribosomal RNA (rRNA) operons of the archaea reflect both the unity and the diversity of this third primary taxon. They have proven to be a rich source of both molecular biological and phylogenetic information. PMID- 1905073 TI - Renal transplantation with cyclosporine in the elderly population. PMID- 1905074 TI - Malnutrition is lethal, diagnosable, and treatable in ESRD patients. PMID- 1905075 TI - The intestinal habitat for organized lymphoid tissues in ruminants; comparative aspects of structure, function and development. AB - Unlike the Peyer's patches of rats and mice, which are considered to be secondary lymphoid organs, the ileal Peyer's patch of sheep is thought to be responsible for the primary generation of B cells, like the bursa of Fabricius of birds. The ileal Peyer's patch of sheep shows prenatal maturation, antigen-independent lymphopoiesis, a rate of lymphocyte production larger than that of the thymus, and involution at a young age. Follicles contain few T cells and have an IgM+, relatively immature B lymphocyte population, as judged by B-cell differentiation markers. The follicle-associated epithelium of the ileal Peyer's patch is of a special type that sheds carbonic anhydrase-rich, 50-nanometer membrane-bounded particles (carbonic anhydrase-reactive particles; CAP) into the intercellular spaces. The CAP filter into the follicle centre and are taken up by lymphocytes. They represent the epithelial (bursa-like) element in an otherwise mesenchymal stroma of reticular cells embedding the follicle lymphocytes. Transepithelial transport of macromolecules, with the formation of multivesicular body-like cytoplasmic vacuoles, appears to be the basis for CAP formation. The jejunal Peyer's patches are devoid of CAP, persist in the adult animal, contain M cells with clusters of B cells in the follicle-associated epithelium, and have many CD4+ lymphocytes in the follicles and in the interfollicular areas. Aggregates of lymphoid follicles in the large intestine resemble the jejunal Peyer's patches with respect to their lymphocyte population and the ileal Peyer's patch with respect to their follicle-associated epithelium. PMID- 1905076 TI - Effect of vitamin A deficiency on the activity of macrophages in Newcastle disease virus-infected chickens. AB - The effect of vitamin A deficiency on the activity of peritoneal macrophages (PM) was investigated in noninfected and Newcastle disease virus (NDV)-infected chickens. Day-old chickens with limited vitamin A reserves were fed diets containing either marginal (120 retinol equivalents (RE)/kg) or adequate (1200 RE/kg) levels of vitamin A. At 4 weeks of age, half of the chickens in each group were infected with the La Sota strain of NDV and PM were isolated 11 or 12 days later. These were used for counting the uptake of fluorescein isothiocyanate labeled yeast cells as an indicator of phagocytic activity and for measuring the reduction of nitroblue tetrazolium (NBT), which provides an estimate of oxygen dependent killing of microorganisms. Vitamin A deficiency impaired NBT reduction and, to a lesser extent, phagocytosis in both infected and noninfected chickens. NDV infection increased phagocytosis and NBT reduction in normal and, to a lesser extent, in vitamin A-deficient chickens. PMID- 1905077 TI - A colorimetric assay for quantitating bovine neutrophil bactericidal activity. AB - A colorimetric assay was developed for quantitating bovine neutrophil bactericidal activity against Staphylococcus aureus. The procedure used the tetrazolium compound, 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT). The assay was conducted by incubating antibody-opsonized S. aureus with neutrophils in microtiter plates for 1 h at a ratio of 10 bacteria per neutrophil. Neutrophils were then lysed with saponin. The MTT was added and samples were incubated for 10 min. Live S. aureus reduced MTT to purple formazan. Dead bacteria and lysed neutrophils did not react with MTT. Bacterially-reduced formazan was solubilized by adding isopropanol and formazan production was quantitated by measuring absorption at 560 nm. Absorption of formazan was directly related to viable bacteria cell number and was used to determine the number of S. aureus not killed by neutrophils. The percentage of bacteria killed by neutrophils was determined by extrapolation from a standard formazan curve that was derived by incubating MTT with known numbers of S. aureus. The colorimetric MTT assay detected suppressed bactericidal activity after in vitro treatment of bovine neutrophils with colchicine, cytochalasin B, or phorbol 12 myristate 13-acetate. In vitro treatment of neutrophils with low levels of recombinant bovine interferon gamma (rBoIFN-gamma) enhanced bactericidal activity, whereas high levels decreased activity. These results suggest the colorimetric MTT bactericidal assay is efficacious in detecting modulation of bovine neutrophil bactericidal activity. Furthermore, the MTT assay has many advantages over traditional bactericidal assays in that it is sensitive, inexpensive, requires less than 3 h to complete, and can analyze many neutrophil samples in a single day. PMID- 1905078 TI - Golgi complex localization of the Punta Toro virus G2 protein requires its association with the G1 protein. AB - The glycoproteins of bunyaviruses accumulate in membranes of the Golgi complex, where virus maturation occurs by budding. In this study we have constructed a series of full length or truncated mutants of the G2 glycoprotein of Punta Toro virus (PTV), a member of the Phlebovirus genus of the Bunyaviridae, and investigated their transport properties. The results indicate that the hydrophobic domain preceding the G2 glycoprotein can function as a translocational signal peptide, and that the hydrophobic domain near the C terminus serves as a membrane anchor. A G2 glycoprotein construct with an extra hydrophobic sequence derived from the N-terminal NSM region was stably retained in the ER, and was unable to be transported to the Golgi complex. The full-length G2 glycoprotein, when expressed on its own, was transported out of the ER and expressed on the cell surface, whereas the G1 and G2 proteins when expressed together are retained in the Golgi complex. A truncated anchor-minus form of the G2 glycoprotein was found to be secreted into the culture medium, but was retained in the Golgi complex when coexpressed with the G1 glycoprotein. These results indicate that the G2 membrane glycoprotein is a class I membrane protein which does not contain a signal sufficient for Golgi retention, and suggest that its Golgi localization is a result of association with the G1 glycoprotein. PMID- 1905080 TI - Synthesis of template-sense, single-strand Flockhouse virus RNA in a cell-free replication system. AB - Cell-free extracts of Drosophila melanogaster cells infected with FHV (Flockhouse virus) have the capacity to synthesize FHV RNA. When such extracts are incubated appropriately, ss and ds FHV RNA 1, -2, and -3 can be detected as synthesis products. Pulse-chase analyses indicate that radioactivity, incorporated into ds RNA 1, -2, and -3 is chased into ss RNA 1, -2, and -3, suggesting that these ds RNAs are intermediates in FHV RNA replication. When the cell-free extracts are treated with detergents to solubilize cellular membranes, only ds RNA 1, -2, and 3 can be detected as synthesis products. The cell-free extracts, treated with a ribonuclease to remove endogenous templates, have the capacity to replicate FHV RNA 1 and -2 when these RNAs are provided as templates, together with lipofectin. Both ss and ds RNA 1 and -2 are detected as synthesis products. When RNA3 is provided as a template, only ds RNA3 is synthesized. In the absence of lipofectin or in the presence of detergent, only ds RNAs are detected as synthesis products and all the incorporated radioactivity is found in the strand complementary to that of the template. Our results are consistent with a mechanism in which second strand synthesis, although not complementary strand synthesis, requires intact membranes. They also suggest that ds RNA3 is an intermediate in the synthesis of ss RNA3. PMID- 1905081 TI - [Serotyping and pyocin typing of Pseudomonas aeruginosa in a study of intrahospital infections]. AB - Typing of Pseudomonas aeruginosa strains is the necessary precondition for the study and control of intrahospital infection caused by this microorganism. Since O-serotype is considered to be the basic epidemiological marker we have studied presence and distribution of some O-serotypes of 235 Pseudomonas aeruginosa strains isolated from 131 patients. The following O-serotypes have been most frequently found: O11 (21%), O6 (18%) and O12 (16%). The combination of sero and pyocin typing proved the presence of epidemic strains at departments of burns and orthopedics. PMID- 1905079 TI - Regulation of the phage phi 29 prohead shape and size by the portal vertex. AB - Bacteriophage phi 29 of Bacillus subtilis packages its double-stranded DNA into a preformed prohead during morphogenesis. The prohead is composed of the scaffold protein gp7, the capsid protein pg8, the portal protein gp10, and the dispensable head fiber protein gp8.5. Our objective was to elucidate the phi 29 prohead assembly pathway and to define the factors that determine prohead shape and size. The structural genes of the phi 29 prohead were cloned and expressed in Escherichia coli individually or in combination to study form determination. The scaffold protein was purified from E. coli as a soluble monomer. In vivo and in vitro studies showed that the scaffolding protein interacted with both the portal vertex and capsid proteins. When the scaffold protein interacted only with the capsid protein in vivo, particles were formed with variable size and shape. However, in the presence of the portal vertex protein, particles with uniform size and shape were produced in vivo. SDS-PAGE analysis showed that the latter particles contained the proteins of the scaffold, capsid, head fiber, and portal vertex. These results suggest that the scaffolding protein serves as the linkage between the portal vertex and the capsid proteins, and that the portal vertex plays a crucial role in regulating the size and shape of the prohead. PMID- 1905083 TI - Combined solvent-detergent and 100 degrees C (boiling) sterilizing dry-heat treatment of factor VIII concentrates to assure sterility. PMID- 1905082 TI - Characterization of autoantibodies in mixed-type autoimmune hemolytic anemia. AB - Three of 46 patients with autoimmune hemolytic anemia (AIHA) satisfied the diagnostic criteria for mixed-type AIHA in which both warm-type and cold-type autoantibodies against red blood cells (RBCs) are present. The specificities of these autoantibodies were analyzed. All of the warm-type autoantibodies were IgG chi, and the specificities were not serologically classified. The autoantibody of patient 1 reacted to the 41- and 80-kD peptides on immunoblotting, and the epitope corresponding to it was papain sensitive. Two warm-type autoantibodies from patients 2 and 3 resembled each other in serological analyses and reacted with a protease- and neuraminidase-resistant antigen. However, the antigen corresponding to the autoantibody of patient 3 was located on the 37-kD peptide by immunoprecipitation. All of the cold-type autoantibodies were IgM-cha and showed high titer and high thermal amplitude. According to the reaction pattern with untreated and enzyme-treated RBCs, the cold-type autoantibodies of patients 2 and 3 were revealed to be anti-Om and anti-I, respectively. In patient 1, the cold-type autoantibody was characterized as having high affinity for autologous RBCs, but its specificity was unclassified. The antigens corresponding to the cold-type autoantibodies were not located by immunoblotting and immunoprecipitation. These serological and immunochemical approaches to autoantibodies in mixed-type AIHA revealed that the warm and cold components recognized the different antigens. PMID- 1905084 TI - A highly purified factor VIII:c concentrate prepared from cryoprecipitate by ion exchange chromatography. AB - A new ion-exchange chromatographic procedure has been developed to produce a highly purified factor VIII (FVIII) concentrate from plasma cryoprecipitate. Solubilized cryoprecipitate, after adsorption on aluminium hydroxide and cold precipitation, was treated with 0.3% tri(n-butyl)phosphate and 1% Tween 80 at 25 degrees C for at least 8 h to inactivate lipid-enveloped viruses. The fraction was then loaded onto a column packed with DEAE-Fractogel TSK 650 M and chromatographed. Most proteins and TnBP-Tween 80 flowed through the gel unretarded. FVIII:c, which bound to the gel, was eluted by increasing the ionic strength, then was directly filter-sterilized without ultrafiltration or addition of a protein stabilizer. Chromatographic recovery of FVIII:c was 80-90%. After freeze-drying, FVIII:c was at a concentration of 42.5 +/- 9.5 IU/ml and had a specific activity of 175.4 +/- 37.8 IU/mg (n = 40), corresponding to a purification factor of over 12,000 from plasma. The typical yield of the freeze dried FVIII:c from cryoprecipitate was 55-65%. FVIII:c was stable for over 24 h at room temperature in the liquid state. The mean content of fibrinogen and immunoglobulin G was only 65 and 100 mg/l, respectively, corresponding to 1.4 and 2.3 mg/1,000 IU FVIII:c. This concentrate, which is much purer than traditional FVIII concentrates, has been found to be well tolerated and effective in clinical treatment of hemophilia A patients. PMID- 1905085 TI - Nordic recommended dietary allowances for omega 3 and omega 6 fatty acids. PMID- 1905086 TI - Effects of omega 3 and omega 6 polyunsaturated fatty acids on the action of cardiac glycosides on cultured rat myocardial cells. PMID- 1905087 TI - Balance between omega 3 and omega 6 fatty acids in heart muscle in relation to diet, stress and ageing. PMID- 1905088 TI - Dietary omega 3 and omega 6 fatty acids and cardiovascular responses to pressor and depressor stimuli. PMID- 1905089 TI - Influence of glycerol trinitrate on contractions of isolated guinea pig tracheas induced by electrical field stimulation. AB - Electrical field stimulation induces cholinergic concentrations of isolated guinea pig tracheal preparations. Glycerol trinitrate increases these contractions at concentrations ranging from 10(-5) M to 10(-6) M, whereas a concentration of 10(-4) M induces strong inhibition of these reactions. PMID- 1905090 TI - [Lysekil and Skene]. PMID- 1905091 TI - [Acute viral hepatitis in Switzerland: physicians' reports from 1984 to 1987]. AB - In 1983, the regulation on reporting transmissible diseases was extended. At that time, the doctors were obliged to report all cases of acute viral hepatitis to the Cantonal physician. The Federal Office of Health commissioned a statistical evaluation of the reports from the years 1984 to 1987. Of the 4543 reports analysed, 40% relate to hepatitis A, 47% to hepatitis B and 7% to non-A non-B hepatitis. Men suffered hepatitis more frequently than women, with the exception of the non-A non-B hepatitis, where the sexes are roughly equally represented. Adolescents and young adults are the most frequently affected age group for all types of hepatitis. Those dependent on drugs have a particularly high risk of infection for all types of hepatitis. The cases of hepatitis occurring after journeys abroad are even more significant in terms of numbers. The medical personnel can no longer be regarded as a high-risk group. An age-standardized comparison shows that, with regard to hepatitis B, the risk for men in medical professions is the same as the average risk for all men, while the risk for women is still slightly higher than that for the female population as a whole. PMID- 1905092 TI - Effect of different inhibitors on the intracellularly and extracellularly generated chemiluminescence induced by formylmethionyl-leucyl-phenylalanine in polymorphonuclear leukocytes. Cellular response in the presence of mannitol, benzoate, taurine, indomethacin and NDGA. AB - When polymorphonuclear leukocytes (PMNL) interact with the soluble stimulus formylmethionyl-leucyl-phenylalanine (FMLP), the cells increase their production of oxidative metabolites. This increased production can be measured as lumino amplified light emission or chemiluminescence (CL). In the present report, experimental systems which allow a quantitation of extracellularly and intracellularly generated metabolites have been used, and the effect of mannitol, benzoate, taurine, indomethacin and nordihydroguaiaretic acid has been investigated. The presence of the hypochlorous acid scavenger taurine had no effect on the intracellular response, whereas the extracellular response was reduced with around 50%. The hydroxyl radical scavenger mannitol had only minor effects on the response, whereas benzoate, another hydroxyl radical scavenger, reduced the extracellular response with around 50% and the intracellular response with more than 90%. Indomethacin, an inhibitor of arachidonic acid metabolism, did not influence the response, whereas NDGA, also an inhibitor of the arachidonic acid metabolism, totally abolished both the extracellular and the intracellular response. The use of scavengers/inhibitors as a means of determining the mechanisms of light emission, and the origin of chemiluminescence produced by neutrophils stimulated by FMLP is discussed. PMID- 1905093 TI - Extra-weak chemiluminescence of drugs. XI. Quenching effects of purine and pyrimidine derivatives on the extra-weak chemiluminescence derived from the Maillard reaction. AB - Quenching effects of purine and pyrimidine derivatives on the extra-weak chemiluminescence (CL) derived from the Maillard reaction of L-lysine with D arabinose were investigated. The pyrimidine derivatives 2'-deoxy cytidine, uridine, and uracil quenched the CL. Cytidine did not quench the CL. Purine derivatives, e.g. uric acid and 1-methyl adenosine were particularly effective in quenching the CL. 5-Methyl adenine and xanthine also quenched the CL, but adenosine had no effect. A comparison of the CL-quenching abilities of compounds that have common basic structure was made; those with ribose at the 5-position were the strongest quenchers. A linear relationship between CL-quenching activity and the HOMO energy of the pi orbital for the various compounds was shown. PMID- 1905094 TI - N5-(1-carboxyethyl)ornithine and related [N-carboxyalkyl]-amino acids: structure, biosynthesis, and function. PMID- 1905095 TI - Structural studies of pig lens aldose reductase: reversible dimerization of the enzyme. PMID- 1905096 TI - cDNA cloning and expression of human aldose reductase. PMID- 1905097 TI - In vitro expression of human placental aldose reductase in Escherichia coli. PMID- 1905098 TI - Purification of aldose and aldehyde reductases from dog kidney. PMID- 1905099 TI - Distribution of dimeric dihydrodiol dehydrogenase in pig tissues and its role in carbonyl metabolism. PMID- 1905100 TI - Reactivity of enzyme modification reagents with aldose reductase and aldehyde reductase. PMID- 1905101 TI - A kinetic perspective on the peculiarity of aldose reductase. PMID- 1905102 TI - Biochemical, immunological, and molecular characterization of a "high Km" aldehyde dehydrogenase. PMID- 1905103 TI - Thyrotropin response to thyrotropin-releasing hormone in elderly patients with and without acute illness. AB - The response of thyrotropin (TSH) to thyrotropin-releasing hormone (TRH) was measured in 70 clinically euthyroid elderly patients who were acutely ill and in 70 age- and sex-matched euthyroid controls who were free of acute disease. The incremental TSH response (delta TSH) was often blunted (less than 2 mU/l) in both groups, though more often in those with acute illness (30%) than in those without (19%). However, in patients from both groups who had a blunted delta TSH, there was often a substantial proportional rise in TSH. A substantial proportional TSH rise may be useful in differentiating between genuine thyroid disease and euthyroid sick syndrome in elderly patients with a blunted delta TSH. PMID- 1905104 TI - Boarding out as an option for the care of elderly people. AB - There has been some experiment in Ireland in recent years with boarding out of elderly persons. This comprises the placement, usually with a non-relative in a private household, of an elderly person, with the carer receiving some reward. This study assesses the cost of care for a small group of elderly persons in boarding-out care compared with a similarly dependent group of elderly persons in welfare home institutional care. The cost of boarding out care is less than half the cost of care in the welfare home. This result is encouraging given the feeling that quality of care in boarding out is not below that of institutional care. PMID- 1905105 TI - Multiple signaling pathways of histamine H2 receptors. AB - Histamine H2 receptor (H2R) has been shown to be coupled to adenylate cyclase. However, we have previously demonstrated that H2R-specific stimulation also activated phospholipase C in human HL-60 promyelocytic leukemia cells (Mitsuhashi M. et al. J. Biol. Chem. 264:18356, 1989). We have extended these studies on HL 60 cells to investigate whether histamine-bovine serum albumin conjugates (HA BSA) specifically recognize H2R and activate phospholipase C pathways. Both histamine (HA) and HA-BSA increased intracellular concentrations of calcium in a H2R specific manner. However, HA-induced calcium mobilization was transient and returned to the basal level within 1-2 min, whereas HA-BSA-induced calcium mobilization was sustained for more than 10 min as a result of the additional influx of extracellular calcium. More interestingly, fluorescein (FITC) labeled HA-BSA was less incorporated into cytosols and present in the membrane fractions for more than 60 min, whereas membrane-bound FITC-HA was rapidly incorporated into cytosols. Furthermore, the levels of inositol 1,3,4,5-tetrakisphosphate, which is known to activate calcium channels were more sustained after HA-BSA stimulation than those of HA alone. These data suggest that H2R activation mechanism is more complex and may be modified by this slowly metabolized "compound ligand". PMID- 1905106 TI - [Report: complications of continent urinary diversion surgery and bladder replacement]. PMID- 1905107 TI - Platelet antiaggregate activity. AB - Calcium ions act as a second messenger to platelet agonists, with increases in intracellular calcium bringing about changes in shape, aggregation, and release reactions. Changes in platelet function have been reported previously in migraine sufferers and there is evidence that hyperaggregability occurs during a migraine attack. It was decided to assess platelet aggregation with platelet-rich plasma (PRP) from nicardipine-treated migraine sufferers because dihydropyridine derivatives are known to inhibit adenosine diphosphate (ADP)- and epinephrine induced aggregation. Aggregation induced by 1.4 mumol/L arachidonic acid was similar in PRP from control subjects and untreated migraine sufferers, whereas 1 or 2 mumol/L ADP-induced aggregation was lower in PRP from migraine sufferers. Treatment with 20 mg of nicardipine three times daily for 2 months significantly (p less than 0.05) increased 2 mumol/L ADP-induced aggregation. It is concluded that nicardipine was acting either on migraine pathogenic mechanisms or directly on the platelets. PMID- 1905109 TI - Mucopolysaccharidosis type VII (Sly syndrome). Beta-glucuronidase-deficient mucopolysaccharidosis in the dog. PMID- 1905110 TI - Psychiatric inpatient care in the VA: before, during, and after DRG-based budgeting. AB - OBJECTIVE: The authors examined the impact of budgeting based on diagnosis related groups (DRGs) on inpatient psychiatric care in Department of Veterans Affairs (VA) medical centers. DRG-based budgeting was implemented by the VA in 1984 and suspended in 1988. METHOD: Computerized discharge abstracts were obtained for all episodes of VA inpatient care occurring from 1980 through 1989. The number of discharges per year, number of unduplicated patients treated, mean length of stay, total number of bed days of care per unique patient per year, readmission rates, and number of episodes of care per operational bed were determined for psychiatric and nonpsychiatric (medical-surgical) hospitalizations occurring before, during, and after DRG-based budgeting was in effect. RESULTS: In the case of VA psychiatric care, DRG-based budgeting was associated with more episodes of care, shorter lengths of stay, higher readmission rates, and more episodes of care per occupied bed. DRG-based budgeting had similar effects on medical-surgical care, although an increase in the number of episodes of care was not observed. During the first year after this funding mechanism was suspended, changes in both psychiatric and medical-surgical care that were related to DRG based budgeting were slowed and, in some cases, reversed. CONCLUSIONS: Both psychiatric and medical-surgical inpatient care in the VA were sensitive to changes in funding mechanisms. These changes were generally similar to those observed in psychiatric care provided by non-VA hospitals reimbursed under Medicare's DRG-based prospective payment system. PMID- 1905108 TI - Homology of the amyloid beta protein precursor in monkey and human supports a primate model for beta amyloidosis in Alzheimer's disease. AB - Progressive cerebral deposition of the amyloid beta-protein (A beta P) occurs in Alzheimer's disease and during aging of certain mammals (eg, human, monkey, dog) but not others (eg, mouse, rat). The authors cloned and sequenced a full-length cDNA encoding the beta-protein precursor (beta APP) of cynomolgus monkey. The predicted amino acid sequence of the 695-residue protein is completely homologous to that of human. The alternatively transcribed exons encoding the Kunitz protease inhibitor region in monkey were cloned, showing only a single conservative amino acid substitution in the 751-residue form of beta APP and four substitutions in beta APP770. Immunoblots of cerebral cortex with antibodies to various beta APP domains showed highly similar beta APP polypeptides in human and monkey, in contrast to those of mouse and rat. The latter differences reflect sequence substitutions, transcriptional regulation, and possibly post translational modifications that may decrease the amyloidogenic potential of rodent beta APP. Immunocytochemistry of aged cynomolgus brain showed A beta P deposited in blood vessels and diffuse and compacted plaques closely resembling those of humans, and the presence of beta-amyloid-associated proteins (alpha 1 antichymotrypsin; complements C1q and C3c) characteristic of A beta P deposits in Alzheimer's disease. The authors' findings demonstrate that cynomolgus monkey and perhaps other primates provide a close animal model for examining the early transcriptional and post-translational processing of beta APP that precedes A beta P deposition during aging and in Alzheimer's disease. PMID- 1905111 TI - The impact of time in treatment on the employment and earnings of drug abusers. AB - We use data from a longitudinal survey to estimate the effects of time in drug abuse treatment on post-treatment weeks worked and earnings for 2,420 clients in three treatment modalities. The regression analysis shows that time in treatment had a positive and statistically significant impact on these labor market outcomes, but the effects were small for all modalities. Although residential clients experienced the largest relative changes in weeks worked and real earnings, a benefit-cost calculation suggests that additional residential treatment cannot be justified from earnings improvements alone. These results may indicate a need for more employment services while in treatment. PMID- 1905112 TI - Farm tractors and mandatory roll-over protection retrofits: potential costs of the policy in New York. AB - Tractor roll-overs are the leading cause of fatal farm accidents, accounting for more than one-fourth of all agriculturally related deaths. Most of these deaths could be prevented if the tractors were equipped with roll-over protective structures (ROPS). This study estimates the number of tractors in New York without ROPS, projects their retirement, and then estimates the number of lives which would be saved if ROPS were retrofitted on old tractors. The basic costs associated with mandating ROPS are calculated from these estimates. The minimum economic cost of mandating ROPS is $511,136 per life saved for the retrofits, and an additional $253,254 per life saved for every $1 million spent annually on enforcement. It is concluded that a policy mandating ROPS on all tractors would be expensive, but should be considered with particular attention to the need for and cost effectiveness of enforcement. PMID- 1905114 TI - The morphology and distribution of photoreceptors in the retina of Bufo marinus. AB - The number, cell morphology and retinal distribution of rods and cones were determined in the retina of the toad, Bufo marinus. Adult animals were sacrificed, both eyes were removed and prepared for either tangential section across the outer segments of the photoreceptor layer, or transverse section across the whole retina. Cone densities increased from an average of 7000/mm2 in the peripheral to a maximum of 25,000/mm2 in the central retina. The high cone densities extended across the naso-temporal axis of the retina corresponding to the position of the visual streak in the ganglion cell layer. The total number of cones in the retina was estimated to be 1.1 million. Rod density of 21,000/mm2 in the central retina decreased to 17,000/mm2 at 1.5-4 mm eccentricity, and then increased to 29,000/mm2 in the peripheral retina. The total number of rods amounted to about 2 million. The mean of the cross-sectional area of rod outer segments was 11.2 +/- 1.5 microns 2 (mean +/- SD) in the highest and 17.9 +/- 4.7 microns 2 in the lowest density areas of the retina. The length of the rod outer segments extended from 28 microns in the ventral peripheral retina to a maximum of 89 microns in the dorsal retina, dorsal to the visual streak of the ganglion cell layer. The results of the present study showed a differential retinal distribution of photoreceptors, with a peak density in the retinal centre and a higher density along the naso-temporal axis of the eye. We conclude that the area of high photoreceptor density, matched by high neuron densities of the INL and GCL, corresponds to the site of acute vision of the Bufo retina. PMID- 1905113 TI - Renal carbonic anhydrase in the quail Coturnix coturnix japonica. II. Changes of enzyme activity in developing and regressing mesonephros. AB - Carbonic anhydrase activity was studied during development and regression of the quail mesonephros by in situ and extra situm investigation. A close correlation was noted between enzyme expression and tissue morphofunctional state. Carbonic anhydrase appears in early development; its highest activity is reached when the kidney is actively secreting, followed by a decrease concomitant with tissue involution. The main localization of the reaction product is the distal tubule showing strongly positive cells intercalated with clear, negative ones. In the functional organ, staining was found at the level of transitional and connecting segments and Wolffian duct. The comparison with the histochemical pattern of the quail metanephros suggests that the functional meaning of renal carbonic anhydrase might be the same both in transitory and in permanent kidney. PMID- 1905115 TI - Serologic and blood culture survey of Trypanosoma cruzi infection in four canine populations of southern Louisiana. AB - Blood culture and serologic testing were used to study the prevalence of Trypanosoma cruzi infection in a group of 85 dogs from southern Louisiana rural environment. These dogs were known to have been in contact with wild mammalian hosts of the hemoflagellate. Results were compared with blood culture and serologic test results in 103 dogs from a rural environment and with limited known wild mammalian T cruzi host contact. Serologic test results for the 188 dogs from the rural environment were compared with results for 176 dogs from an urban animal shelter and for 100 household pet dogs from an urban southern Louisiana environment. Blood culture was not performed on urban dogs. Culture results were negative in all dogs from rural environments. Serologic evidence of infection was obtained for 4 of the 85 (4.7%) dogs of rural environment with known host contact. Of 176 dogs from the animal shelter, 4 (2.3%) had high antibody titer to T cruzi, and 11 others had low titer (less than 2 adjusted ELISA units [aEU]). Two and 4 dogs of the housed urban and rural groups, respectively, had antibody titer to T cruzi that was less than 2 aEU. Results indicate that prevalence for exposure to T cruzi antigen is higher in dogs with high potential contact with the vector and wild mammalian hosts of T cruzi, whether they are from rural or urban environment. Furthermore, results indicate that similar studies on high-risk human populations may be indicated. PMID- 1905116 TI - Endoscopically placed nasoenteral feeding tubes. Indications and techniques. AB - We reviewed indications, techniques, and results for endoscopic placement of nasoenteral feeding tubes by analyzing records of 29 hospitalized patients who had undergone 41 tube placements. Indications included gastric stasis after gastric surgery (11 patients), gastroparesis and reflux or both in critically ill trauma patients (10), stricture secondary to vertical banded gastroplasty (3), and partial gastric outlet obstruction (5). Two endoscopic techniques were used. The guidewire method in which a flexible, Silastic feeding tube is advanced over the guidewire to the desired site had 82 per cent success (22 of 27). Adjunct fluoroscopy achieved a 94 per cent success rate (17 of 18); success without fluoroscopy was 56 per cent (5 of 9). The pull-along method attached a suture to the feeding tube tip which was grasped with forceps and moved to the correct location (93% success; 13 of 14). Fluoroscopy was not used with this method. Feeding tubes were successfully placed in 35 of 41 attempts (85%) in 27 of 29 patients. Failures were caused by an inability to intubate the efferent limb of a gastrojejunostomy (2) and unrecognized guidewire movement (4). Tube use ranged from one day to six months. We conclude that endoscopic placement of nasoenteral feeding tubes is an effective means to establish a route for enteral nutrition in selected patients. PMID- 1905117 TI - Tracheostomy. A new indication for percutaneous endoscopic gastrostomy tube placement. AB - A review of patients undergoing elective tracheostomy (TRACH) and percutaneous endoscopic gastrostomy (PEG) was undertaken to decide whether addition of PEG to a planned tracheostomy was safe and indicated by conditions mandating the tracheostomy. Charts were reviewed for demographic data, details of operation, outcome, and disposition. Sixteen patients with an average age of 61 years were studied. Primary diagnosis included CNS disease (7), trauma (6), and multisystem failure (3). These patients had 35 associated diseases. Indications for tracheostomy were respiratory failure (9) and prolonged intubation (7). The average time from admission to procedure was 23.7 days. Average operative time was 50 minutes. There were three postoperative complications. Ten patients were discharged (5 home, 5 skilled facility) and six expired. All patients had functioning tracheostomies and PEGs at the time of disposition. Percutaneous endoscopic gastrostomy is a logical adjunct to planned tracheostomy, adding little morbidity but with potential benefit to long-term management in this special group of chronic care patients. PMID- 1905118 TI - Percutaneous endoscopic jejunostomy in a patient with previous esophagectomy. AB - Establishment of a percutaneous endoscopic jejunostomy via direct jejunal puncture was accomplished in a 45-year-old woman five years after a partial esophagectomy with cervical esophagogastrostomy for adenocarcinoma of the esophagus. The patient had recurrence of the cancer at the anastomotic site with subsequent inability to eat, necessitating a feeding tube for prolonged enteral nutrition. Although percutaneous puncture of the jejunum has been previously described, it has been limited to patients who had undergone partial or complete gastrectomies with Bilroth II anastomoses. This case report of direct endoscopic jejunal tube placement in a patient after esophagectomy further establishes this procedure as a viable alternative to surgically placed feeding tubes in patients with altered gastric anatomy. PMID- 1905120 TI - [Immunegene rearrangements of acute undifferentiated leukemia (AUL)]. AB - Acute unclassified/undifferentiated leukemia (AUL) is classified into following 3 subgroups; 1) cases with coexpression of myeloid and lymphoid antigens on a single blast, 2) cases with coexistence of heterogenous subpopulations, 3) cases showing lineage-switch during the clinical course. Most cases in the groups 2 and 3 were not different from those in group 1 because of the presence of one or more common antigen (s) on the blasts. Accordingly, AUL can be considered as a candidate of leukemia arising form multipotential stem cells and the phenotype and genotype are represent a potential for myeloid and lymphoid differentiation. We should recognize that dual genotypes of IgH and TCR genes in B-precursor cell leukemia differ from such multipotentiality of leukemic cells, because the genotype occurs in re-arrangement process for IgH gene diversity after malignant transformation. PMID- 1905119 TI - [Nervous tumors of the infratemporal fossa]. AB - Six cases of neurogenic tumors developing in the infratemporal fossa are reported. These are neuromas or neurofibromas in 5 cases and meningioma in 1 case only. The first 4 cases are primary tumors of the infratemporal fossa, while the last 2 tumors have developed into the temporal fossa from neighboring lesions. Computed tomography and RMI are irreplaceable techniques to assess the extension of such tumors and their connection with the neighboring organs, and to guide the treatment, which must be surgical whenever possible. Complete exeresis of the tumor is difficult. These examinations are also essential for follow-up and for the early detection of possible recurrence. PMID- 1905121 TI - [In vivo assessment on the therapeutic effects of etoposide, vincristine and mitomycin C against human neuroblastoma]. AB - Anti-tumor effects of etoposide (VP-16), vincristine and mitomycin C were evaluated with four human neuroblastoma xenograft, according to Battelle Columbus Laboratories protocol. Etoposide is one of the agents which has been reported to be effective against advanced neuroblastoma clinically, if combined with other agents. While vincristine was effective against 1 out 4 neuroblastoma xenografts, TS-N-2, with 58.1% maximum inhibition rate, etoposide was assessed ineffective as a single agent in all of the 3 xenografts used. Since etoposide had no effect on the weight gain in nude mice in this xenograft experiment, the dose of etoposide was increased two-fold against 2 xenografts, but found ineffective also in the increased dose. Mitomycin C, which has not been used in childhood malignant tumors, was effective against 2 out of 4 xenografts, TNB-9 and SK-N-AS, with 72.0% and 78.4% maximum inhibition rates, respectively. PMID- 1905122 TI - [A case of inoperable advanced gastric cancer with effective treatment by local administration of OK-432, intra-abdominal administration of CDDP, and long-term high-dose mitomycin C, and UFT]. AB - A 61-year-old male diagnosed as Borrmann type 3 advanced gastric cancer was operated, but could not be resected because of the invasion to the pancreas and the lymph nodes metastases. So, local administration of OK-432 20 KE, intra abdominal administration of CDDP 50 mg, and long-term intermittent intravenous administration of MMC a total amount of 1480 mg, and oral administration of UFT were performed. As the result of this therapy, the tumor was reduced in size. Three years and seven months after the operation, he feels well. Because of this combined therapy, his renal function was made worse. PMID- 1905124 TI - Continued need for pneumococcal prophylaxis after splenectomy. PMID- 1905125 TI - [Use of ospen (a drug form of phenoxymethylpenicillin) in pediatric practice]. AB - Ospen is a dosage form of phenoxymethylpenicilin. As a therapeutic and prophylactic agent it was shown efficient in treatment of patients with diseases of the otorhinolaryngological organs due to primary and secondary coccal infections. High antiinflammatory activity of ospen was observed in acute and aggravated chronic tonsillitis, otitis, sinusitis and acute respiratory virus infections as well as in prevention of complications after adenotonsillectomy and various manipulations connected with penetration into the inner cavities. Ospen was highly active as a prophylactic agent against hospital respiratory infections. It prevented its distribution and aggravation of the main diseases. Adverse reactions to the use of ospen were minimal and no toxic manifestations were recorded. PMID- 1905123 TI - Thrombosis in systemic lupus erythematosus: a French collaborative study. AB - A retrospective study was undertaken of 120 children with systemic lupus erythematosus (SLE) seen in Paris and its immediate suburbs who fulfilled at least four of the American College of Rheumatology diagnostic criteria for SLE, and in whom the disease was diagnosed before the age of 16 and between January 1975 and December 1987. Eleven of these children (eight girls and three boys) all more than 10 years of age (mean follow up 8.1 years; range 3-13) had thrombotic episodes (9%). Thrombosis was one of the presenting signs in seven patients; in five it was associated with typical symptoms of SLE, and in the other two the thrombotic episode was isolated and diagnosis of SLE was delayed one and three years. Of a total of 16 thrombotic episodes (six of which were recurrent), 14 involved the leg veins, and in four there was associated pulmonary embolism. There were two episodes that affected cerebral arteries. The American College of Rheumatology diagnostic criteria for SLE as well as the incidence of lupus anticoagulant, positive direct Coombs test, and vasculitis in this group of patients was compared with the incidence in patients with SLE but no thrombosis. Only lupus anticoagulant was significantly associated with thrombotic episodes: eight of 11 (73%) of patients with SLE and thrombotic (arterial or venous) episodes had lupus anticoagulant compared with only 10 of 74 patients (14%) with no history of thrombotic events in the same age group. PMID- 1905127 TI - Polyhalogenated dibenzo-p-dioxins and dibenzofurans and the immune system. 2. In vitro effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on lymphocytes of venous blood from man and a non-human primate (Callithrix jacchus). AB - The effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on poke weed mitogen stimulated proliferation and differentiation of peripheral lymphocytes was studied in vitro with cells from a non-human primate (marmoset monkey, Callithrix jacchus) and from man. Monoclonal antibodies and flow cytometry (FACScan) were used for analysis. The extent of the overall mitogen-stimulated proliferation of isolated lymphocytes in vitro from marmoset blood was only slightly reduced in the presence of TCDD compared to the solvent control (0.01% DMSO). However, incubation with TCDD in the culture medium together with the mitogen led to a pronounced decrease in the percentage of the lymphocyte subset with the surface marker CD4, and a concomitant increase in the percentage of CD8+ cells. The lowest concentration found to be effective in vitro was 1 x 10(-13) M TCDD (25 fg TCDD/ml). When culturing lymphocytes from human blood of different donors under identical conditions in the presence of TCDD and the mitogen, corresponding effects were observed to those seen with marmoset cells. A closer analysis of the T lymphocyte subsets affected revealed the CD4+ CDw29+ (helper-inducer cells) to be the main target for the action of TCDD. A clear-cut change in the percentage of this subpopulation was induced at concentrations as low as 1 x 10(-13) M TCDD. The development of the IL-2-marker in culture was only slightly affected by TCDD, and concentrations of 1 x 10(-12) M were required to slightly reduce the number of CD2+CD25+ cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1905126 TI - [Imidazoles in the treatment of ocular mycoses]. AB - The use of a new class of broad spectrum antifungal drugs i.e. imidazoles and in particular ketoconazole in treatment of severe affections of the eye such as mycoses is described. The clinical trials included 40 patients with various forms of mycosis: mycotic canaliculitis (6 patients), mycotic blepharitis (4 patients), mycotic conjunctivitis (7 patients), keratomycosis (17 patients) and mycotic endophthalmitis (6 patients). Ketoconazole was used in the form of tablets and instillations. The combined treatment included nonsteroid antiinflammatory drugs and antibacterial agents. The clinical trials showed that ketoconazole had pronounced antifungal activity and was rather efficient in treatment of ocular mycoses. Its broad spectrum and low toxicity were recorded. PMID- 1905128 TI - [Ovarian steroid synthesis in tissue culture after administration of hormones and epidermal growth factor]. AB - The features of steroidogenesis of immature mouse ovaries in culture under the influence of follicle-stimulating hormones (FSH), human chorionic gonadotropin (hCG), epidermal growth factor (EGF) and insulin have been investigated during the period of reinitiation of meiosis in the oocytes. Secretion of progesterone is stimulated after addition of FSH, hCG and of insulin and EGF combination to the medium. EGF increases FSH-stimulated progesterone secretion and inhibits estradiol secretion. The ratios progesterone/estradiol and testosterone/estradiol increase, when EGF is added to the culture medium. It is analogous to the action of hCG. It is suggested that EGF may be an intrafollicular EGF regulator of luteinizing hormone action on the sex and somatic cells of the mammalian ovaries. PMID- 1905129 TI - Baroreflex responsiveness during hypobaric hypoxia. AB - Baroreflex responses to graded neck suction during held expiration were studied in five healthy females at sea level and at a simulated altitude of 4,572 m (15,000 ft), with and without oxygen administration. An apparent resetting of the baroreflex was observed during hypobaric hypoxia, but this effect was abolished by oxygen administration. Held expiration alone induced a pulse prolongation in all experimental conditions, however this bradycardiac response was smaller during hypobaric hypoxia than during the two normoxic conditions. When the bradycardic responses of held expiration were subtracted, the baroreflex responses to neck suction were equal in all experimental situations. Similarly, the baroreflex was unaffected by hypobaric hypoxia when the R-R interval prolongations were expressed in percentage of the R-R intervals immediately prior to the neck suction. These data indicate that reduced ambient pressure per se has no influence on the carotid baroreflex control of heart rate. PMID- 1905130 TI - T lymphocyte-synovial fibroblast interactions induced by mycobacterial proteins in rheumatoid arthritis. AB - An in vitro system was established in which single-cell suspensions of lymphocytes and synovial cells from the joints of patients with rheumatoid arthritis were cultured and produced an outgrowth of an organized inflammatory tissue with an extracellular matrix and capsule. The tissue outgrowth, which had histologic features of pannus, required the addition of mycobacterial antigen and interleukin-2 to the tissue culture medium and was dependent upon the presence of T lymphocytes and their interaction with synovial fibroblasts. PMID- 1905131 TI - An evaluation of electrocardiograms before and after nitroglycerin therapy. PMID- 1905132 TI - Delayed recovery from lithium neurotoxicity. AB - Recovery from lithium-induced neurotoxicity can take much longer than the 2 to 3 weeks previously reported. Contributing factors could include advanced age and underlying clinical or subclinical brain disease. However, the occurrence of lithium-induced neurotoxicity does not preclude reinstitution of lithium treatment. We report three case histories that illustrate these points. PMID- 1905133 TI - The management of dementia: an issue of growing concern. Report of a conference. PMID- 1905134 TI - An approach to the functional analysis of lecithin-cholesterol acyltransferase. Activation by recombinant normal and mutagenized apolipoprotein AI. AB - Apolipoprotein AI (apo AI) of human serum high-density lipoprotein functions as an activator of lecithin-cholesterol acyltransferase (LCAT) and therefore plays an important role in reversed cholesterol transport. The mechanism of the acyltransfer, the activating polypeptide domains of apo AI and the active site of LCAT in this transesterification are not yet known. Synthetic peptides of the apo AI sequence have been designed to determine the activating structure, but did not yet lead to conclusive results. This also applies to spontaneous apo AI mutants. We therefore used the method of site-directed mutagenesis of apo AI cDNAs using the overlap extension approach by the polymerase chain reaction. These constructs were cloned into the procaryotic vector pET8c and expressed under the inducible T7 promoter. The engineered apo AI polypeptides were isolated and purified by affinity chromatography and assayed for their activator activity. The essentials of this approach to the structure and function of activators in general have successfully been exemplified for the LCAT activation by engineering apo AI mutant polypeptides a) by the deletion of two adjacent amphipathic helices (amino acid residues 146-186) and b) by introducing a point mutation (Glu111----Gln). PMID- 1905135 TI - Purification of factor VIII:c coagulant activity from rat liver nonparenchymal cell culture medium by immobilized metal ion affinity chromatography. AB - The purification of factor VIII:c coagulant activity on the basis of its affinity for calcium is described. For this purpose, use was made of a recently introduced chelating matrix, i.e., carboxymethylated aspartic acid agarose, coupled with calcium--thereby creating a gel with specificity comparable with biospecific affinity chromatography. In a single step factor VIII:c activity was purified from rat liver nonparenchymal cell culture medium with a purification factor of 85-fold. The material exhibits a single band on polyacrylamide gel electrophoresis. PMID- 1905136 TI - Stabilization of human prostatic acid phosphatase by coupling with chondroitin sulfate. AB - Human prostatic acid phosphatase (PAP) (EC 3.1.3.2) was covalently linked to chondroitin sulfate A from whale cartilage. In order to bind the protein amino groups with the preactivated carboxyl groups of chondroitin sulfate, 1-ethyl-3 (3'-dimethylaminepropyl)carbodiimide and N-hydroxysulfosuccinimide were used as coupling agents. The product was soluble and enzymatically active. The activity was on average 25% higher than that of the free enzyme. The product was heterogeneous in respect to charge and Mr (50-1500) kDa, as determined by chromatography on Sephacryl S 300 and polyacrylamide gel electrophoresis. The resulting polymers contained covalently bound chondroitin sulfate, as shown by the biotin-avidin test. The modified enzyme is more resistant against various denaturing agents, e.g., urea, ethanol, and heat. Thus covalent modification of PAP by cross-linking to chondroitin sulfate could be the preferred method for stabilization of its biological activity. PMID- 1905137 TI - Purification and some properties of Pseudomonas fluorescens lipase. AB - Lipase (triacylglycerol lipase, EC 3.1.1.3) has been purified from Pseudomonas fluorescens wild strain by chromatography on DEAE-cellulose and octyl-Sepharose CL-4B. The yield was 21% and the specific activity of the purified enzyme 4780 U/mg protein. It showed a Mr of about 45 x 10(4) by sodium dodecyl sulfate polyacrylamide gel electrophoresis. The enzyme is active over a wide pH range and at 50-55 degrees C. PMID- 1905138 TI - Interferon-gamma and chronic granulomatous disease. AB - The molecular and biochemical characterization of many components of the phagocyte oxidase complex that generates superoxide have greatly advanced our understanding of this important pathway. Genetic defects in one or more of the components of this host defense system result in the chronic granulomatous disease phenotype. Biochemical advances and the results of a clinical trial that established the efficacy of recombinant human interferon-gamma for prophylaxis of infections in chronic granulomatous disease are the highlights of recent achievements in this area of phagocyte biology. PMID- 1905139 TI - Implementing nutritional therapy in the thermally injured patient. AB - Providing adequate nutritional support is an important adjuvant therapy in the management of thermal injuries. Technological advances in both enteral and parenteral nutrition have enabled clinicians to administer large amounts of essential nutrients to critically ill patients who frequently cannot or will not take these nutrients orally. The use of any method of nutritional support requires careful administration and scheduled monitoring to ensure its safety and efficacy. Critical care nurses have an integral role in assuring that appropriate nursing care and monitoring measures are performed. PMID- 1905140 TI - G proteins (Gi, Go) in the medial temporal lobe in schizophrenia: preliminary report of a neurochemical correlate of structural change. AB - We have measured the amount of Gi (the inhibitory G-protein) or Go (a similar G protein of unknown function) in 5 areas of the medial temporal lobe of control and schizophrenic brains utilizing pertussis toxin-catalyzed ADP ribosylation. The material used has previously been shown to have asymmetrical structural abnormalities of the ventricular system. The amount of Gi or Go was reduced on the left side in the hippocampus, amygdala and parahippocampal gyrus, the difference reaching significance in the hippocampus. This data is the first report of a neurochemical correlate of the structural change in the brains of patients with schizophrenia. Decreased Gi or Go in hippocampus may relate to other reported neurochemical deficits or other transmembrane signalling abnormalities. Further investigations of these indices of secondary messenger function in relation to structural changes are indicated. PMID- 1905141 TI - Purification and characterization of purine nucleoside phosphorylase from developing embryos of Hyalomma dromedarii. AB - Purine nucleoside phosphorylase from Hyalomma dromedarii, the camel tick, was purified to apparent homogeneity. A molecular weight of 56,000 - 58,000 was estimated for both the native and denatured enzyme, suggesting that the enzyme is monomeric. Unlike purine nucleoside phosphorylase preparations from other tissues, the H. dromedarii enzyme was unstable in the presence of beta mercaptoethanol. The enzyme had a sharp pH optimum at pH 6.5. It catalyzed the phosphorolysis and arsenolysis of ribo- and deoxyribo-nucleosides of hypoxanthine and guanine, but not of adenine or pyrimidine nucleosides. The Km values of the enzyme at the optimal pH for inosine, deoxyinosine, guanosine, and deoxyguanosine were 0.31, 0.67, 0.55, and 0.33 mM, respectively. Inactivation and kinetic studies suggested that histidine and cysteine residues were essential for activity. The pKa values determined for catalytic ionizable groups were 6-7 and 8 9. The enzyme was completely inactivated by thiol reagents and reactivated by excess beta-mercaptoethanol. The enzyme was also susceptible to pH-dependent photooxidation in the presence of methylene blue, implicating histidine. Initial velocity studies showed an intersecting pattern of double-reciprocal plots of the data, consistent with a sequential mechanism. PMID- 1905142 TI - Sequences of the variable regions of three monoclonal antibodies specific for histidine-containing protein of the bacterial phosphoenolpyruvate:sugar phosphotransferase system. AB - The variable regions of three monoclonal antibodies, Jel 42, Jel 44, and Jel 324, specific for the histidine-containing protein of the bacterial phosphoenolpyruvate:sugar phosphotransferase system have been sequenced from their respective mRNAs. The Vh gene families were deduced from the percent homology to the concensus gene sequences and the J gene and D gene usage was also analysed. PMID- 1905143 TI - DNA polymerase delta mediates excision repair in growing cells damaged with ultraviolet radiation. AB - In confluent, stationary phase cells, an aphidicolin-sensitive DNA polymerase mediates UV-induced excision repair, but the situation in growing cells is still controversial. The sensitivity of repair synthesis to aphidicolin, an inhibitor of DNA polymerases alpha and delta, was determined in growth phase and confluent normal human fibroblasts (AG1518) using several techniques. Repair synthesis in confluent cells was always inhibited by aphidicolin, no matter which measurement technique was used. However, the inhibition of repair synthesis in growth-phase cells by aphidicolin was only detectable when techniques unaffected by changes in nucleotide metabolism were used. We conclude that UV-induced repair synthesis in growing cells is actually aphidicolin sensitive, but that this inhibition can be obscured by changes in nucleotide metabolism. Employing butylphenyl deoxyguanosine triphosphate, a potent inhibitor of polymerase alpha and a weak inhibitor of delta, we have obtained evidence that polymerase delta is responsible for repair synthesis in growth-phase cells following UV irradiation. PMID- 1905144 TI - Genome fingerprinting as a typing method used on polyagglutinable Pseudomonas aeruginosa isolates from cystic fibrosis patients. AB - Phenotypical changes occur in the surface of Pseudomonas aeruginosa during the chronic lung infection of cystic fibrosis patients. It is difficult with the classical typing methods, such as serotyping, phage typing and pyocin typing, to decide if a patient has been colonized with a new strain or whether it is the same strain which has reappeared, for instance after chemotherapy in the lungs. This investigation was carried out to evaluate genome fingerprinting as a typing method and to see how it correlated with classical methods and with DNA probe typing. Forty Pseudomonas aeruginosa isolates, 34 polyagglutinable and six monoagglutinable, from 14 cystic fibrosis patients were analysed using genome fingerprinting. The bacterial chromosomes were digested with the restriction endonucleases Dra 1 and Xbal, and separated by field inversion gel electrophoresis. The results were compared with those of a previous work (Ojeniyi et al. 1990) concerning typing with a DNA probe, serotyping using both polyclonal and monoclonal sera, phage typing, pyocin typing and reverse phage typing. The results of genome fingerprinting and DNA probe typing showed the best correlation, followed by pyocin typing. The correlation between the results of genome typing and the other typing methods was low. The discriminatory effect of genome fingerprinting was higher than that of DNA probe typing, and genome fingerprinting was found to be the best single method for epidemiological investigations of polyagglutinable isolates from cystic fibrosis patients. PMID- 1905145 TI - Human antibody response to the major adhesin of Mycoplasma pneumoniae: increase in titers against synthetic peptides in patients with pneumonia. AB - Peptides corresponding to parts of the P1 protein (major adhesin) of Mycoplasma pneumoniae were synthesized. On the basis of predicted antigenicity, seven sequences containing 17 to 21 amino acids were selected. In addition, one peptide containing a sequence of 13 amino acids shown to be related to cytadherence of M. pneumoniae was included. Serum samples from 56 patients with pneumonia were tested for a rise in titers of specific IgG during infection, using the peptides as coating antigens in ELISA. A titer rise against one or more peptides was observed in 10 out of 13 patients with serological evidence of mycoplasmal etiology. Specific antibodies to two or more peptides were demonstrated in three patients, whereas seven patients responded to one peptide only. In the sera from patients with pneumonia of non-mycoplasmal etiology, no titer rises above the cut off level were observed. Our results indicate that a combination of four peptides would be possible for use as antigen for serological diagnosis of infections with M. pneumoniae. PMID- 1905146 TI - Muscarinic suppression of the M-current is mediated by a rise in internal Ca2+ concentration. AB - The role of intracellular Ca2+ in the muscarinic suppression of M-current was examined. Intracellular injection of Ca2+ buffer into cells in the intact ganglion reduced the response to muscarinic agonist. In similar experiments on isolated cells, Ca2+ buffer was introduced into the cytoplasm using a perfused recording pipette. Ca2+ buffer (20 mM) with the free Ca2+ concentration set to normal resting levels produced a reversible reduction of the muscarinic response. In a second line of investigation, it was found that pharmacological procedures designed to deplete internal stores of Ca2+ produced a decrease in the muscarinic response. These results, taken together with previous work, support the hypothesis that the muscarinic suppression of M-current is mediated by the release of Ca2+ from intracellular stores. PMID- 1905147 TI - Vitamin D metabolism and serum binding proteins in anorexia nervosa. AB - Serum vitamin D metabolites and other parameters of mineral metabolism were measured in 12 patients with anorexia nervosa. Serum concentrations of calcium, phosphate, albumin, alkaline phosphatase, parathyroid hormone, calcitonin, osteocalcin, and 24-hours calcium excretion were normal. Serum 25-hydroxyvitamin D (25OHD) concentration was similar in patients and normal subjects, whereas 1,25 dihydroxyvitamin D (1,25(OH)2D) levels were significantly reduced in patients (62 +/- 17 vs 82 +/- 17 pmol/l); p less than 0.05). The concentration of vitamin D binding protein (DBP) in patients was normal, but serum binding capacity (Nmax) was diminished in anorectic patients (2.05 +/- 0.50 vs 2.53 +/- 0.51 mumol/l; p less than 0.05). The diminished serum binding capacity, in spite of normal concentrations of albumin and DBP, reflects the presence of qualitative rather than quantitative defects in serum transport proteins. Since the reduction in 1,25(OH)2D and serum binding capacity was quantitatively similar, it is likely that free 1,25(OH)2D levels would be normal. PMID- 1905148 TI - Effects of an EDTA infusion on the urinary elimination of several elements in healthy subjects. AB - Ethylene diamine tetraacetate calcium disodium salt (EDTA Ca Na2), 1 g dissolved in 250 ml of 5% w/v glucose solution, was infused intravenously over 1 h into 10 healthy subjects (eight males and two females). Urines were collected over 24 h, the day before and on the day of the EDTA Ca Na2 infusion test. The elements Al, B, Ba, Cu, Fe, Mn, Si, Sr, Zn, Na, K, Ca, Mg, S and P were measured by inductively coupled plasma optical emission spectrometry. Pb was measured by inductively coupled plasma mass spectrometry. The EDTA Ca Na2 infusion increased the 24 h elimination of Al from 9.8 micrograms to 58 micrograms, of Fe from 66 to 121 micrograms, of Mn from 2.9 to 16.5 micrograms, of Pb from 9.8 to 56 micrograms and of Zn from 623 to 8847 micrograms. The ratio of the increase of urinary elimination induced by EDTA Ca Na2 was about 2 for Fe, 5 for Al, Pb and Mn, and 15 for Zn. PMID- 1905149 TI - Heavy metals, chlorinated pesticides and polychlorinated biphenyls in sudden infant death syndrome (SIDS). AB - The concentrations of lead in blood and of cadmium and mercury in kidney tissue were determined by atomic absorption spectrometry in cases in SIDS and a control group containing cases of known causes of death. SIDS cases were split into groups from urban and rural areas and areas highly polluted with lead and zinc (sites of lead and zinc works). Neither the concentration of lead in blood (median 26.5 to 50.0 micrograms/l), nor the concentration of cadmium (median 24.0 to 44.0 micrograms/kg ww) or mercury (43.0 to 69.0 micrograms/kg ww) showed significant differences between the groups. In addition the concentrations of persistent chlorohydrocarbons (hexachlorbenzene; alpha, beta and gamma hexachlorcyclohexane; heptachlorepoxide; dieldrine; total DDT; polychlorinated biphenyls) were measured in subcutaneous fatty tissue in SIDS cases from rural and urban areas and in a control group. These substances also showed no significant concentration differences in cases of SIDS. PMID- 1905150 TI - Phase II trial of ifosfamide in recurrent and metastatic head and neck cancer. AB - Thirty-six patients with recurrent carcinoma of the head and neck and no prior exposure to chemotherapy were treated with Ifosfamide. This drug was administered, concomitantly with Mesna, as a 24-hr infusion at a dose of 5-6.25 g/m2 every 3 weeks. Objective activity in 32 evaluable patients was 28% (9/32, 95% C.I. 17%-39%); 40% of patients had leukocyte values less than 2000 mm3 and 6% platelets less than 50,000 mm3. Nonhematologic toxicity consisted mainly of nausea/vomiting (66% greater than or equal to grade 2) and alopecia (80% greater than or equal to grade 2). The activity encountered warrants further studies with this drug in head and neck cancer. PMID- 1905151 TI - Free fatty acid accumulation in secretagogue-stimulated pancreatic islets and effects of arachidonate on depolarization-induced insulin secretion. AB - Free fatty acids in isolated pancreatic islets have been quantified by gas chromatography-mass spectrometry after stimulation with insulin secretagogues. The fuel secretagogue D-glucose has been found to induce little change in islet palmitate levels but does induce the accumulation of sufficient unesterified arachidonate by mass to achieve an increment in cellular levels of 38-75 microM. Little of this free arachidonate is released into the perifusion medium, and most remains associated with the islets. Glucose-induced hydrolysis of arachidonate from islet cell phospholipids is reflected by release of the arachidonate metabolite prostaglandin E2 (PGE2) from perifused islets. Both the depolarizing insulin secretagogue tolbutamide (which is thought to act by inducing closure of beta-cell ATP-sensitive K+ channels and the influx of extracellular Ca2+ through voltage-dependent channels) and the calcium ionophore A23187 have also been found to induce free arachidonate accumulation within and PGE2 release from islets. Surprisingly, a major fraction of glucose-induced eicosanoid release was found not to require Ca2+ influx and occurred even in Ca(2+)-free medium, in the presence of the Ca(2+)-chelating agent EGTA, and in the presence of the Ca2+ channel blockers verapamil and nifedipine. Exogenous arachidonic acid was found to amplify the insulin secretory response of perifused islets to submaximally depolarizing concentrations of KCl, and the maximally effective concentration of arachidonate was 30-40 microM. These observations suggest that glucose-induced phospholipid hydrolysis and free arachidonate accumulation in pancreatic islets are not simply epiphenomena associated with Ca2+ influx and that arachidonate accumulation may play a role in the signaling process which leads to insulin secretion. PMID- 1905152 TI - The NADH-binding subunit of the energy-transducing NADH-ubiquinone oxidoreductase of Paracoccus denitrificans: gene cloning and deduced primary structure. AB - The NADH dehydrogenase complex isolated from Paracoccus denitrificans is composed of approximately 10 unlike polypeptides and contains noncovalently bound FMN, non heme iron, and acid-labile sulfide [Yagi, T. (1986) Arch. Biochem. Biophys. 250, 302-311]. The NADH-binding subunit (Mr = 50,000) of this enzyme complex was identified by direct photoaffinity labeling with [32P]NADH [Yagi, T., & Dinh, T.M. (1990) Biochemistry 29, 5515-5520]. Primers were synthesized on the basis of the N-terminal amino acid sequence of this polypeptide, and these primers were used to synthesize an oligonucleotide probe by the polymerase chain reaction. This probe was utilized to isolate the gene encoding the NADH-binding subunit from a genomic library of P. denitrificans. The nucleotide sequence of the gene and the deduced amino acid sequence of the entire NADH-binding subunit were determined. The NADH-binding subunit has 431 amino acid residues and a calculated molecular weight of 47,191. The encoded protein contains a putative NAD(H) binding and an iron-sulfur cluster-binding consensus sequence. The deduced amino acid sequence of the Paracoccus NADH-binding subunit shows remarkable similarity to the alpha subunit of the NAD-linked hydrogenase of Alcaligenes eutrophus H16. When partial DNA sequencing of the regions surrounding the gene encoding the NADH binding subunit was carried out, sequences homologous to the 24-, 49-, and 75-kDa polypeptides of bovine complex I were detected, suggesting that the structural genes of the Paracoccus NADH dehydrogenase complex constitute a gene cluster. PMID- 1905153 TI - Reductive alkylation of DNA by mitomycin A, a mitomycin with high redox potential. AB - The mitomycins are a group of antitumor antibiotics that covalently bind to DNA upon reductive activation. Mitomycin A (1b; MA) is more toxic than its clinically useful mitomycin C (1a; MC). The greater toxicity of mitomycin A has been previously attributed to its higher reduction potential. In this report, the DNA alkylation products of reductively activated MA were isolated and characterized by conversion to the known 7-amino mitosene-deoxyguanosine adducts. The three major adducts formed were identified as a monoadduct, N2-(2"beta-amino-7" methoxymitosen-1"alpha-yl)- 2'-deoxyguanosine (5), a decarbamoyl monoadduct, N2 (2"beta-amino-10"-decarbamoyl-7"-methoxymitosen-1"alpha-y l)-2'- deoxyguanosine (6), and a bisadduct, N2-(2"beta-amino-10"-deoxyguanosin-N2-yl-7-methoxymitosen 1" alpha- yl)-2'-deoxyguanosine (7). Under all reductive activation conditions employed, MA selectively alkylated the 2-amino group of guanine in DNA, like MC. In addition, both MA and MC alkylated DNA and cross-linked oligonucleotides to a similar extent. However, variations in the reductive activation conditions (H2/PtO2, Na2S2O4, or enzymatic) affected the distribution of the three major MA adducts in a different manner than the distribution of MC adducts was affected. A mechanism is proposed wherein the 7-methoxy substituent of MA allows initial indiscriminate activation of either of the drugs' two electrophilic sites. While oxygen inhibited cross-linking by MC, similar aerobic conditions exhibited little influence on the cross-linking ability of MA. Hence, the greater toxicity of MA may be influenced by increased and nonselective activation and cross-link formation in both aerobic and anaerobic cells. This effect is a direct consequence of the higher redox potential of MA as compared to MC. PMID- 1905154 TI - Cell-free biosynthesis of surfactin, a cyclic lipopeptide produced by Bacillus subtilis. AB - The lipopeptide antibiotic surfactin is a potent extracellular biosurfactant produced by various Bacillus subtilis strains. Biosynthesis of surfactin was studied in a cell-free system prepared from B. subtilis ATCC 21332 and OKB 105, which is a transformant producing surfactin in high yield [Nakano, M. M., Marahiel, M. A., & Zuber, P. (1988) J. Bacteriol. 170, 5662-5668]. Cell material was disintegrated by treatment with lysozyme and French press. A cell-free extract was prepared by ammonium sulfate fractionation, which catalyzed the formation of surfactin at the expense of ATP. Lipopeptide biosynthesis required the L-amino acid components of surfactin and D-3-hydroxytetradecanoyl-coenzyme A thioester. D-Leucine which is present in surfactin was not utilized but inhibited the biosynthetic process. The structure of surfactin, synthesized enzymatically in vitro, was confirmed by chromatographic comparison with the authentic compound and by amino acid analyses. An enzyme fraction was prepared by gel permeation chromatography which catalyzed ATP/pyrophosphate exchange reactions dependent on the component amino acids of surfactin. This enzyme fraction was capable of binding substrate amino acids covalently, probably via thioester linkages. The formation of these intermediates was inhibited by various thiol blocking reagents and phenylmethanesulfonyl fluoride. De novo synthesis of the lipopeptide was not observed with this partially purified enzyme fraction most likely due to the lack of an acyltransferase activity required for linking the beta-hydroxy fatty acid to the peptide moiety. PMID- 1905155 TI - Screening for pharyngeal gonorrhea in adolescents. A reexamination. AB - The cost-effectiveness of screening for pharyngeal gonorrhea (PG) in an adolescent clinic population was examined in the context of dramatically decreasing prevalence. Chart review revealed that the apparent PG prevalence had decreased from 15/555 (2.7%) 8 years ago to 0/319 (0.0%) recently in the clinic population studied. The earlier high prevalence of PG probably represented poor laboratory test specificity. Cost analysis showed that only at very high prevalence of PG (greater than 8%) would pharyngeal screening be cost-effective unless PG can be shown to be an important source of genital infection. We concluded that continued pharyngeal screening is not justified in our clinic because prevalence is so low. PMID- 1905156 TI - Ca(2+)-independent phospholipase A2 activity associated with secretory granular membranes in rat parotid gland. AB - Phospholipase A2 activity was detected in a secretory granular fraction (SG) purified by Percoll gradient centrifugation from rat parotid gland using [3H]phosphatidylcholine (PC) as a substrate. High activity of this enzyme was observed at neutral pH. The enzyme was activated by Triton X-100 and did not require Ca2+ for its activity. In the absence of Ca2+, its apparent Km for exogenous PC was 28 microM while it was slightly increased by adding 5 mM CaCl2 (73 microM). Furthermore, the enzyme was located essentially in a granular membrane fraction separated from granular lysate. The deacylation activities were also detected in other subcellular fractions, which showed a different detergent susceptibility or pH-dependency from that in SG. These results suggest that secretory granules have membrane-bound phospholipase A2 which has properties different from that found in other organelles. PMID- 1905157 TI - A two component-type cytochrome P-450 monooxygenase system in a prokaryote that catalyzes hydroxylation of ML-236B to pravastatin, a tissue-selective inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase. AB - Pravastatin (CS-514) is a tissue selective inhibitor of 3-hydroxy-3 methylglutaryl coenzyme A reductase (EC 1.1.1.34), a key enzyme in cholesterol biosynthesis. This compound is obtained by hydroxylation of ML-236B (mevastatin) in Streptomyces carbophilus catalyzed by a cytochrome P-450sca monooxygenase system. NADH-cytochrome P-450 reductase was purified to homogeneity from S. carbophilus as a single polypeptide chain with a molecular weight of 51 kDa, and reconstituted the hydroxylation in vitro with cytochrome P-450sca, NADH and O2. This protein contained FAD and FMN molecule. The FMN molecule was easily dissociated from the reductase, and had a Kd value of 5 x 10(-5) M. The cytochrome P-450sca monooxygenase system was present in the soluble fraction and consisted of only two components, cytochrome P-450sca and flavoprotein. Our results constitute the demonstration of a two component-type cytochrome P-450 system in a prokaryote. PMID- 1905158 TI - Regulation of expression of the genome of bacteriophage M13. Gene V protein regulated translation of the mRNAs encoded by genes I, III, V and X. AB - With the aid of a binary plasmid in vivo testsystem it was demonstrated that the single-stranded DNA binding protein encoded by gene V of bacteriophage M13 not only regulates the synthesis of its cognate DNA replication proteins at the level of translation, but also of the assembly proteins and the coat proteins encoded by genes I and II, respectively. Furthermore, gene V protein functions as a translational autoregulator of its own synthesis. Comparison of the mRNA levels of genes I and X in the presence and absence of wild-type gene V protein indicated that gene V protein augments the physical stability of these mRNAs. The expression of the Escherichia coli beta-galactosidase gene and of a gene X mutant containing a deletion in the nontranslated mRNA leader sequence was not influenced by gene V protein, lending support to the conclusion that gene V protein exerts its regulatory effect via a specific nucleotide sequence in the leader sequences of the respective M13 mRNAs. We conclude that gene V protein functions as a master regulatory protein of the expression and replication of the M13 genome. PMID- 1905159 TI - [An increase in brain temperature in rats to the intranasal administration of thyroliberin]. AB - The integral rat brain temperature was measured by radiothermoscope after intranasal instillation of thyroliberin in a dose 400 mkg. The recording increase of temperature lasted during two hours after instillation. This phenomenon is based both on the direct action of thyroliberin and on its capacity to stimulate the induction of other regulatory peptides. PMID- 1905160 TI - CO2-sensitivity in newborn and young infants tested by the rebreathing method. Methodological aspects. AB - The rebreathing method in newborn and young infants was tested with regard to the effects of increasing levels of CO2 on the behavioral state and to the influence of facial stimulation caused by the use of a face mask and pneumotachograph on the breathing pattern. Successive increases in inspired CO2 levels from 3 to 8.5% did not change the behavioral state. The application or removal of a face mask, with or without an attached pneumotachograph, caused an immediate disruption in the breathing pattern which lasted 10-40 s. Thereafter, breathing stabilized. When only the face mask was used, the increases in minute ventilation, tidal volume and cycle duration of 7, 13 and 5%, respectively, were transient and lasted for 40-50 breaths. The breathing then returned to control levels. In contrast, breathing through the face mask connected to the pneumotachograph caused a long-lasting increase in ventilation (12%) due to the retention of CO2 in the spirometric circuit. We conclude that the inhalation of a continuously increasing mixture of 3-8.5% CO2 in O2 did not influence the behavioral state and that the effect of face mask on breathing pattern was transient. PMID- 1905161 TI - Thyroid function in fetus and mother during the second half of normal pregnancy. AB - Thyroid hormones, thyroxine-binding globulin (TBG) and thryrotropin (TSH) concentrations were measured in 46 paired fetal and maternal blood samples collected between 17 and 36 weeks of gestation. The samples were selected retrospectively from fetuses that had undergone cordocentesis for prenatal diagnosis, had been found to be unaffected and confirmed healthy at birth. In maternal serum, total thyroxine (TT4) and triiodothyronine (TT3) concentrations were high, but free thyroxine (FT4) and free triiodothyronine (FT3) were within normal adult ranges; reverse T3 (RT3) increased and TSH levels decreased towards term. Fetal TT4, FT4, TT3, FT3, TBG and TSH levels significantly increased whereas RT3 sharply decreased with gestational age. The ratio of fetal TSH/FT4 significantly decreased, suggesting that the set point for negative feedback of pituitary TSH secretion is changing while the sensitivity of the thyroid gland to TSH increases throughout gestation. There was no significant correlation between the maternal and fetal TBG, TSH, TT4 and FT4, whereas maternal TT3 was positively correlated with fetal TT4, FT4, TT3 and FT3. Normal reference values for maternal and fetal iodothyronines, TBG and TSH throughout the second half of gestation provide insight into fetal thyroid development and may be useful for prenatal diagnosis. PMID- 1905162 TI - Brain dysfunction during motor activation and corpus callosum alterations in schizophrenia measured by cerebral blood flow and magnetic resonance imaging. AB - Sixteen unmedicated (14 never-medicated, 2 with washout periods of 1-2 weeks) schizophrenic patients displaying positive symptoms (e.g., formal thought disorder, hallucinations, delusions) without negative symptoms (e.g., flattening of affect, loss of energy, anhedonia--type I patients), 15 unmedicated (with washout periods from 1 week to 2 years) patients with marked negative symptomatology [type II patients; criterion score below 15/above 35 on the Munich version of the Scale of Assessment of Negative Symptoms (SANS), respectively], and 31 matched normal controls were investigated using regional cerebral blood flow [rCBF; dynamic single-photon emission computerized tomography (SPECT) with Xenon-133 as tracer] and magnetic resonance imaging (MRI; spin-echo technique, T1 weighted, midsagittal cuts). rCBF measurements were performed during both resting conditions and simple motor activation. Separately, on the same day, we performed a planimetric evaluation of the callosal-brain ratio in all subjects using MRI. In accordance with previous results on a smaller sample, we found signs of diffuse bilateral rCBF hyperactivation in type I patients, as compared with signs of nonreactivity in type II schizophrenics. Both activation patterns were different from a strictly contralateral sensorimotor rCBF activation seen in normal persons (only 8 studied with SPECT). The planimetry of relative callosal area did not reveal differences compared to normal persons, when type I/II patients were taken together. However, the threefold increased variance as compared with that found in normal persons suggested biological heterogeneity in patients. We found an increase of relative callosal size in type I as compared with type II patients. In the light of some recent findings linking lack of laterality of several brain functions to increased callosal size, we propose lack of laterality/diffuse hyperactivation and increased callosal size to be connected with positive symptomatology/good prognosis schizophrenia, and vice versa. PMID- 1905163 TI - Interpretation of the thyrotropin (TSH) response to thyrotropin-releasing hormone (TRH): implications of an improved TSH assay system. PMID- 1905164 TI - [Development and evaluation of a multi-applicator system of endocavitary radiothermotherapy of gynecologic tumors]. AB - An applicator system for the radiothermotherapy of gynecological tumors has been developed. The concept is based on combining high-dose rate afterloading therapy with local hyperthermia (27.12 MHz). The main applicator, the rf-gamma applicator consists of a guide tube for the gamma source, an electrode system and a cooling system. Isodoses and isotherms can be adapted to the individual anatomical pathological situation presenting. For therapy planning the interaction between the applicators and the perfused tissue was investigated in a theoretical FEM model. In the first step, the SAR-function in the vicinity of the rf-applicator was determined by means of a 2D FEM calculation. In a second step, the 3D temperature fields was determined using linear shape functions. The results of these calculations showed that in every case the hot spots shifted from the applicator surface into the depths of the tissue. With the aid of an infrared camera and a split phantom the calculations were examined in a homogeneous non perfused tissue model. Thermometry confirmed the accuracy of the results obtained. The radiothermotherapy system described here was tested in animal experiments, and is presently being used in a clinical pilot study. PMID- 1905165 TI - [The induction of the monooxygenase system and the incorporation of the radioactive label from 2-14C-lysine into the liver microsome fraction of rats exposed to phenobarbital against a background of deficiencies in lysine, methionine, threonine and vitamins A, C and E]. AB - The effect of diet on induction of monooxygenases and distribution of label from 2-14C-lysine in fractions of liver homogenate, muscle homogenate and blood of male rats treated with phenobarbital (80 mg/kg, three days) was studied. 2-14C lysine was injected intraperitoneally 24 h before the first injection of phenobarbital. It was demonstrated that monoxygenase induction, increase of relative liver weight and incorporation of label from 2-14C-lysine into fractions of liver homogenate in phenobarbital-treated rats were more pronounced as compared with the similarly treated rats that were fed a balanced diet. The possibility of mobilization of deficient essential components to liver from other organs and tissues for maintenance of monoxygenase induction is discussed. PMID- 1905166 TI - [Carbonic anhydrase III--a marker of the myoepithelial cells of human salivary glands]. AB - Carbonic anhydrase III (CAIII) is the isoenzyme purified from the human skeletal slow muscle immunohistochemically revealed in smooth muscle cells of uterus, myoepithelial cells of salivary, lactiferous and prostatic glands of man. Immunohistochemical determination of CAIII is a useful approach to correct the identification of myoepithelial cells in human salivary glands. PMID- 1905167 TI - Inhibition of chemically-induced skin carcinogenesis in mice by peanut oil preparations. AB - Epidermal hyperplasia and sebaceous gland destruction - good indicators of carcinogenic potential - were studied in short-term mouse skin experiments following application of BaP and TPA dissolved either in a peanut oil mixture or in acetone. Subsequently, the carcinogenicity of BaP and DMBA alone or in association with TPA was dissolved in the same vehicles, and determined in mouse long-term skin tests. In parallel, ODC activity and binding to DNA, RNA and proteins were examined in epidermal cells after exposure to TPA and BaP respectively. When the peanut oil excipient was used as a solvent, a complete inhibition of BaP and TPA activities was observed in short-term skin tests, as well as a complete inhibition of BaP, DMBA and TPA carcinogenicity in long-term tests. TPA-induced ODC activity was suppressed by the peanut oil mixture while BaP binding to nucleic acids and proteins of epidermal cells was only slightly inhibited. These results indicate that the excipient possesses anti-carcinogenic potentials for epidermal cells. The persistence of BaP binding to macromolecules in epidermal cells without tumor development suggests that the carcinogenic action of BaP may include both genotoxic and epigenetic mechanisms. PMID- 1905168 TI - Identification of alcohol-related problems in a general hospital setting: a cost effectiveness evaluation. AB - Alcohol is a major cause of morbidity and mortality. The prevention of alcohol problems would result in significant savings to the NHS and society. Screening is an important step in preventing problems. This study examines the costs of screening patients for alcohol problems. Over a 21-month period doctors, nurses and a specialist worker screened medical and orthopaedic admissions to the York District Hospital. A cost-effectiveness analysis of screening data was carried out. Costs were measured by time taken to screen and the relative costs of employing different occupational groups. Effects included the screening rates of each occupational group and those identified as at risk. Results suggested a greater positive case identification rate could be achieved by employing a specialist worker, but at greater cost. The cost-effectiveness evaluation helps clarify the resource consequences of a screening programme and can be a useful aid in the decision-making process. PMID- 1905169 TI - Recording of information in case notes. PMID- 1905170 TI - Demand for psychogeriatric services. PMID- 1905171 TI - Effects of injection mechanics, pH of infusate and 6-hydroxydopamine on cerebromicrovascular permeability in rats. AB - The effects of altering the rate, manner and vehicle used for intracerebral injection upon microvascular permeability were studied in Sprague-Dawley rats employing horseradish peroxidase histochemistry. The volume of vehicle delivered and the site of intracerebral injection were kept constant. In comparison to continuous infusion, vascular permeability was significantly greater following manual (intermittent) injections; however, no differences were found when the infusion rate was decreased 10-fold. Use of a buffered vehicle (Hanks' balanced salt solution) with pH adjusted to 7.4, in contrast to the more commonly used non buffered vehicle (saline-ascorbate), resulted in significant reductions in permeability. The apparent influence of the agent 6-hydroxydopamine (6-OHDA) on changes in vascular permeability was found to vary depending on the type and pH of the vehicle used for injection. Significantly greater permeability resulted with saline-ascorbate (pH 3.1) as the vehicle when compared to Hanks' balanced salt solution (pH 7.4). Changes in vascular permeability can therefore be produced by varying mechanical and vehicular factors which, in the case of 6 OHDA, far outweigh previously reported permeability changes specifically attributed to this neurotoxin. PMID- 1905172 TI - Synapse formation by autonomic nerves in the previously denervated neuromuscular junctions of the feline intrinsic laryngeal muscles. AB - Nerve terminals of unknown origin at the previously denervated neuromuscular junctions (NMJ) of the feline intrinsic laryngeal muscles were investigated. Until 3 weeks after the transection of the recurrent laryngeal nerve (RLN), no axons were observed in the Bungner's bands and the NMJ, accompanied by a marked decrease of autonomic nerves around the blood vessels. At 5-6 weeks nerve varicosities labeled by 5-hydroxydopamine (5-OHDA) were observed in the Bungner's bands together with an increase of autonomic nerves around the blood vessels. At 9-30 weeks (8 cases) nerve terminals were found at the NMJ in all cases. Even if the ipsilateral vagosympathetic trunk was transected at 17 weeks, nerve terminals were found at all the NMJ 3 weeks after this treatment, indicating that nerve terminals were not from the original RLN. These nerve terminals were considered to be autonomic because nerve terminals labeled by 5-OHDA were observed. Furthermore, in the case of the removal of the superior cervical ganglion (SCG) and the nodose ganglion at 21 weeks, though nerve varicosities were found in the Bungner's bands, nerve terminals were not found 9 days after this treatment, suggesting that the ipsilateral SCG possibly played an important role. In electromyographic findings fibrillation-like activities were recognized in 8/11 cases after 5 weeks. The relationship of this phenomenon to fibrillation and muscle atrophy was discussed. PMID- 1905173 TI - Downregulation of muscarinic receptors in the rat caudate-putamen after lesioning of the ipsilateral nigrostriatal dopamine pathway with 6-hydroxydopamine (6 OHDA): normalization by fetal mesencephalic transplants. AB - The autoradiographic distribution and density of muscarinic receptors was studied in the neostriatum of rats with long-term unilateral 6-hydroxydopamine (6-OHDA) lesions of the nigrostriatal dopaminergic pathway and in lesioned rats who had additionally received embryonic substantia nigra grafts in the dopamine denervated striatum. Muscarinic receptors were labeled with [3H]quinuclidinyl benzilate (QNB), M1 receptors were directly labeled with [3H]pirenzepine (PZ) and non-M1 receptors were labeled by the competition of 100 nM PZ with [3H]QNB. The density and distribution of muscarinic receptors were directly compared to the sodium-dependent, high-affinity, choline uptake sites as labeled with [3H]hemicholinium-3 (HC-3). In the 6-OHDA-lesioned animals, there was a 25% reduction in muscarinic receptors labeled with [3H]QNB. Subtype analysis showed that there was a reduction of both M1 (-26%) and non-M1 (-33%) receptors. A normal density of both muscarinic receptor populations was found in animals with successful transplants. Saturation analysis demonstrated that the changes, in muscarinic receptor density, were due to a change in receptor number (Bmax) and not affinity (Kd). There was no significant change in [3H]HC-3 binding in the 6 OHDA-lesioned or transplanted animals, indicating that alterations in muscarinic receptors were not due to transynaptic degeneration of striatal cholinergic interneurons. The findings of downregulation of muscarinic receptors following long-term dopamine denervation and the subsequent normalization of muscarinic receptor density after fetal mesencephalic transplantation suggests that transplanted substantia nigra cells are able to restore inhibitory control on striatal cholinergic interneurons. PMID- 1905174 TI - Neurobiochemical evidence for calcium-induced depolarization of EGTA-pretreated hippocampal synaptosomes. AB - The neurochemical effects of calcium were determined in hippocampal cholinergic synaptosomes which had been prepared and preincubated in calcium-free medium containing 50 microM EGTA. Calcium (and barium) reversibly stimulated [3H]acetylcholine release and produced a long-lasting elevation of high-affinity [3H]choline uptake. Both effects were blocked by omega-conotoxin and substantially reduced by tetrodotoxin. Together, these data indicate that calcium causes membrane depolarization and is associated with opening of voltage-gated sodium channels in EGTA-pretreated synaptosomes. PMID- 1905175 TI - Specific hippocampal lesions indicate the presence of sulfonylurea binding sites associated to ATP-sensitive K+ channels both post-synaptically and on mossy fibers. AB - The density of glibenclamide (GB) binding sites decreases considerably in the dentate gyrus (greater than 80%), the CA1 field (approximately 75%) and the stratum lucidum of CA3 field (approximately 70%) after intradentate colchicine injections in rat hippocampus. The density of GB receptors is unchanged in kainic acid damaged hippocampus. These data show that GB binding sites associated to adenosine triphosphate-sensitive K+ channels are mainly located in granular cells in both pre- and post-synaptic positions. They are present in mossy fibers. PMID- 1905176 TI - Neurite formation on laminin: effects of a galactosyltransferase on primary sensory neurons. AB - Avian embryonic sensory neurons from ED8 chick possess a trypsin-labile cell surface galactosyltransferase (GalTase) activity that glycosylates laminin in the presence of uridine 5' galactose (UDPgal). In a 4 h biological assay concentration dependent partial inhibition of neurite growth on laminin was observed in the presence of (i) alpha-lactalbumin, a specific inhibitor of the enzyme, (ii) N-acetylglucosamine (GlcNac), the appropriate acceptor substrate, or its polymer chitotriose, and (iii) UDPgal, the catalytic substrate. Prior exposure of substrate-immobilized laminin to glycosidase partially inhibited neurite growth. Alpha-lactalbumin did not influence cell adhesion at saturating concentrations for inhibition of neurite formation. Neurite growth on fibronectin was not inhibited by prior exposure to glycosidase or by alpha-lactalbumin, and fibronectin was not an appropriate substrate for glycosylation by the sensory neurons. These observations extend the catalogue of domains of laminin that subserve neurite growth, and define in functional terms a class of neuronal receptors that interact with lactosaminoglycan-type oligosaccharides of laminin. PMID- 1905177 TI - Contribution of forebrain noradrenaline innervation to the central circulatory effects of alpha-methyldopa and 6-hydroxydopamine. AB - We studied the circulatory effects of chronic lesions of the ascending noradrenergic (NA) projections to the forebrain on the acute effects of intracisternal (i.c.) alpha-methyldopa (alpha-MD) and 6-hydroxydopamine (6-OHDA) on mean arterial pressure (MAP) and heart rate (HR) in conscious rabbits with arterial baroreceptors either intact or denervated (sinoaortic denervation, SAD). Both drugs acutely release neurotransmitter from central NA neurons. I.c. 6-OHDA produced acute hypertension and bradycardia while i.c. alpha-MD produced acute hypotension and bradycardia. The responses are qualitatively similar in SAD rabbits except that after 6-OHDA, HR increased. In another group we studied the effects of the drugs 3-4 weeks after localised injections of 6-OHDA in the midbrain dorsal and ventral NA bundles. Local 6-OHDA depleted forebrain regions of NA by 44-76%, and had no effects on basal values of MAP or HR. The pressor and depressor effects, of 6-OHDA and alpha-MD respectively, were little affected by the lesions in either intact or SAD rabbits. By contrast, in rabbits with intact baroreceptors, the lesion abolished the bradycardia produced by i.c. alpha-MD and 6-OHDA. The latter drug now produced a late tachycardia. In SAD rabbits, however, there was no effect on the alpha-MD-induced bradycardia, but the 6-OHDA tachycardia was enhanced. Since the major effects of the lesions were confined to the rabbits with intact baroreceptor afferents, it suggests that the ascending NA pathways are important for the cardiac responses dependent on baroreceptor input. In intact animals, both drugs produce bradycardia through facilitation of the vagal component of the baroreceptor-heart rate reflex. In SAD rabbits, almost all the changes to HR are mediated through the cardiac sympathetic and the lesions have little effect on HR. PMID- 1905178 TI - Two binding sites for [3H]glibenclamide in the rat brain. AB - The binding of [3H]glibenclamide, a potent sulfonylurea which blocks ATP sensitive potassium channels, was studied in the rat brain. A Scatchard plot of saturation isotherms suggests that [3H]glibenclamide binds in various brain regions to a high- and a low-affinity binding site (Kd values of 0.21 nM and 111 nM and Bmax values of 41 and 1060 fmol/mg protein, respectively). Competitive binding assays with various unlabelled sulfonylureas showed biphasic displacements of [3H]glibenclamide with pseudo-Hill coefficients significantly different from unity. These data indicate the existence of a heterogeneity of binding sites to [3H]glibenclamide in the rat brain; this may correlate with the variability of effects of sulfonylureas observed from physiological experiments. PMID- 1905179 TI - Effect of amphetamine on cerebral blood flow and capillary perfusion. AB - The purpose of this study was to determine the cerebral regional microvascular and vascular responses to amphetamine sulfate at a dose (5 mg/kg) known to affect neuronal function. Cerebral blood flow (14C-iodoantipyrine method) and percent of perfused capillaries (fluorescein isothiocyanate-dextran and alkaline phosphatase staining method) were determined during control and after intravenous administration of amphetamine in conscious Long-Evans rats. Amphetamine caused an increase in blood pressure (34%) and heart rate (31%). There was a significant increase in averaged cerebral blood flow from 98 +/- 8 to 166 +/- 9 ml/min/100 g after amphetamine. This flow increase was significant in the cortex, basal ganglia, pons and medulla, however the increase was not significant in the hypothalamus. In control rats, there were approximately 325 +/- 17 capillaries/mm2 of brain tissue and 52 +/- 1% of them were perfused. Amphetamine increased the percent perfused significantly to 72 +/- 1% in all examined regions. There was a similar significant increase in the percent of perfused cerebral capillary volume fraction. There were both vascular and microvascular responses to amphetamine, increasing cerebral blood flow as well as reducing the diffusion distance for oxygen. PMID- 1905180 TI - Localization of prostaglandin endoperoxide synthase in neurons and glia in monkey brain. AB - The localization of prostaglandin endoperoxide synthase in monkey brain was investigated by the immunoperoxidase method using the monoclonal antibody (PES-7) raised against the enzyme purified from bovine seminal vesicle. The frozen sections with 30-microns thickness were employed after the brain was fixed with perfusion of 2% paraformaldehyde in phosphate-buffered saline. The immunoreactivity was most intense in the neurons of cerebral cortex and hippocampus, and was moderate in the neurons of caudate nucleus, putamen, globus pallidus and amygdala, while it was relatively weak in glial cells in the whole brain regions including the white matter. The majority of neurons showed the immunoreactivity in the somata and proximal dendrites, but exceptionally in the pyramidal cells of the hippocampus, positive staining was also observed in the apical dendrites. In the cerebellum, the immunoreactivity in both neurons and glia was rather faint as compared with that in other regions. Positive staining was not significantly observed in the vasculatures and arachnoid membranes. These findings indicate that most of neuronal and glial cells in monkey brain contain the enzyme of the rate-limiting and initial step of the biosynthesis of prostaglandins which regulate a variety of neural functions. PMID- 1905181 TI - The activity of catecholamine synthesis in the hypothalamus of female normotensive Wistar Kyoto and spontaneously hypertensive rats. AB - The activity of catecholamine synthesis in the hypothalamus, as determined by the rate of 3,4-dihydroxyphenylalanine (DOPA) accumulation after the administration of a DOPA decarboxylase inhibitor, was compared among Wistar, spontaneously hypertensive (SH), and genetically matched normotensive Wistar Kyoto (WKY) rats. DOPA accumulation in the median eminence, an index of the activity of tuberoinfundibular dopaminergic neurons, was greater in SH rats than Wistar and WKY rats while DOPA accumulation in the medial preoptic area was smaller in Wistar rats than SH and WKY rats. No strain difference was found in DOPA accumulation in the corpus striatum, which represents the activity of nigrostriatal dopaminergic neurons. These results suggest that there are differences in catecholamine synthesis in the hypothalamus not only between SH and WKY rats but also between WKY and Wistar rats. PMID- 1905182 TI - [Identification and localization on chromosome 1 of a gene controlling the occurrence of periinsulitis in NOD diabetic mice]. AB - Diabetic NOD (Non Obese Diabetic) mice show early pancreatic infiltration of mononuclear cells around Langerhans islets (periinsulitis). Study of (NOD x C57BL/6) F1 and F2 mice reveals that periinsulitis is constantly associated with a similar infiltration of salivary glands (sialitis) and is controlled by a dominant susceptibility locus. Segregation analysis of periinsulitis and microsatellite DNA markers indicates that the gene controlling periinsulitis maps to chromosome 1, close to the Bcl-2 locus. PMID- 1905183 TI - [Speed of fetal growth: a new methodological approach]. AB - We suggest a new method to calculate fetal growth velocity. Fetal growth curves are divided in small linear units, and corresponding slopes calculated as growth rates. An example is detailed to set out statistical contingencies for methodological reliability. Specific interest of the method is discussed. PMID- 1905184 TI - [Quantification of mRNA coding for enterocyte fatty acid binding proteins (FABP) in rats: effect of high lipid diet and starvation]. AB - We have tested in adult rat the specificity and the sensitivity of two cDNA probes derived from recombinant plasmids pJG19 and pJG418. The Northern blot analysis of total RNA extracted from small bowel reveals 0.9 and 0.7 kb mRNA corresponding respectively to the I and L-FABPc mRNA. A linear relation occurs between the amounts of input total RNA and the quantities of specific mRNA found by hybridization with cDNA probes (r = 0.991 and r = 0.998 for I and L-FABPc respectively). We have also evaluated the effect of drastic nutritional status: a high fat diet containing 45% of lipids and a starvation of three days. A two fold increase in I and L-FABPc mRNA occurs in starved rats. By contrast, only the I FABPc mRNA are slightly enhanced after the hyperlipidic diet (50%). These preliminary results, which must be confirmed by further experiments, suggest a differential nutritional regulation of I and L-FABPc gene expression in rat intestine. PMID- 1905185 TI - [Comparative data on biogenic amines and GABA in three Rodents Filariae]. AB - Detection and quantification of biogenic amines and GABA were carried out on three adult Filariae Litomosoides carinii, Acantocheilonema viteae and Molinema dessetae obtained from Rodents. Catecholamines were under the level of detection. Indolamines and GABA levels depend on species and sex. Results are discussed in relation to the parasitism and localization in the host. PMID- 1905186 TI - [Participation of 5-HT 1A receptors in the decrease by serotonin of activation of locus coeruleus neurons by glutamate]. AB - The serotonin-induced decrease of glutamate-evoked activation of noradrenergic locus coeruleus neurons is mimicked by agonists of 5-HT 1 and 1A but not by 5-HT 1B or by 5-HT 2 agonists. Moreover, this effect is reversed by a broad-spectrum 5 HT antagonist but not by a 5-HT 2 antagonist, indicating that this effect is mediated primarily through 5-HT 1A receptors. PMID- 1905187 TI - [Variation of substance P-like immunoreactivity in plasma and cerebrospinal fluid in the course of arthritis induced by Freund adjuvant in rats, a model for the study of chronic pain]. AB - Parallel time courses of clinical and behavioural parameters and levels of plasma substance P-like immunoreactivity (SPLI-PI) were studied in arthritic rats (adjuvant induced arthritis, AIA, a chronic pain model). Acute (14 and 21 post inoculation days,PI) and post-acute (42 days PI) phases of the syndrome were investigated. These data were compared with those obtained in a control situation (inoculation day). In a second experimental series, levels of substance P-like immunoreactivity in cerebrospinal fluid (SPLI-CSF) were determined at the same stages of AIA. In arthritic rats SPLI-PI was strongly enhanced (X4) as early as 14 days PI and remained increased (X4) at all stages studied, whereas SPLI-LCR was significantly increased (X2) only 21 days PI and returned to control levels at 42 days PI. These data suggest that SP could be distributed in two different pools, a peripheral one of inflammatory origin, and a central one which could be more specific to the chronic pain situation. PMID- 1905189 TI - DNA single stranded gaps formed during DNA repair synthesis induced by methyl methanesulfonate are filled by sequential action of aphidicolin- and dideoxythymidine sensitive DNA polymerases in HeLa cells. AB - DNA repair synthesis induced by methyl methanesulfonate in preconditioned HeLa cells in which DNA replicative synthesis had been highly suppressed was inhibited by aphidicolin (an inhibitor of DNA polymerases alpha and delta) and dideoxythymidine (ddThR, an inhibitor of DNA polymerase beta). Incomplete repair patches sensitive to exonuclease III were accumulated in the presence of aphidicolin while not in the presence of ddThR. These patches were comopleted by the combined action of Klenow fragment and T4 DNA ligase, indicating that the single-stranded gaps were formed during the repair synthesis. Moreover, ddThR had little effect on the repair synthesis in the presence of aphidicolin. Thus, the results suggest that the single-stranded gaps may be sealed first by aphidicolin sensitive polymerase followed by ddThR-sensitive DNA polymerase on the same site of the repair patch. PMID- 1905188 TI - Co-cultures of hepatocytes with epithelial-like cell lines: expression of drug biotransformation activities by hepatocytes. AB - To improve long-term expression of drug biotransformation activities in hepatocytes, we have examined the suitability of several epithelial-like cell lines (MDCK, MS and L-132) for supporting functional co-cultures with rat hepatocytes. Cells were selected on the basis of their compatibility with hepatocytes, formation of stable monolayers in the absence of serum and lack of drug biotransformation activities. The expression of individual elements of the biotransformation system was evaluated in these co-cultures. Co-cultured hepatocytes remained viable and showed a characteristic polygonal shape for more than a week. Depending on the cell line used, levels of aryl hydrocarbon hydroxylase and 7-ethoxycoumarin O-deethylase activities of co-cultured hepatocytes oscillated between 24-47% of their initial value after 4 days in culture. The highest levels of monooxygenase activity were found in hepatocytes co-cultured with MS cells (41-47%). In contrast, these activities decreased to 6% when hepatocytes were maintained in pure culture for the same period. The activities of the conjugating enzymes UDP-glucuronyltransferase and glutathione S transferase were maintained at nearly the initial levels during the complete period of study, both in pure and mixed-cultures, regardless of the cell line used. MS cells adapted themselves much better to serum-free culture conditions, and the co-culture with rat hepatocyte was technically easier. After one week, total cytochrome P450 and reduced glutathione in rat hepatocytes/MS co-cultures were 31% and 127% respectively of the day O values, whereas they were undetectable in pure culture. A clear induction of monooxygenase activities by methylcholanthrene, phenobarbital and ethanol could be observed by the 5th day in MS cells/hepatocyte co-cultures. The fact that the results of our work show the suitability of MS cells, an epithelial-derived cell line, for improving the expression of biotransformation enzymes of cultured hepatocytes opens new possibilities of simplifying co-cultures for their use in drug-metabolism studies. PMID- 1905190 TI - Effect of decreased pH on force and phosphocreatine in mammalian skeletal muscle. AB - Phosphocreatine (PCr) and intracellular pH changes were monitored by 31P-NMR spectroscopy in isolated, arterially perfused cat biceps and soleus muscles, while the pH of the CO2-bicarbonate buffered perfusate was decreased from 7.1-7.4 to 6.4-6.7 by increasing the CO2 in the equilibrating gas from 5 to up to 70%. In biceps (fast twitch) muscles, intracellular pH decreased from 7.0 to 6.6 (30% CO2, 30 degrees C), peak tetanic force decreased by 8%, but the rise and relaxation times of tetanic were not significantly changed. In soleus muscles, intracellular pH decreased from 7.0 to 6.6 (30% CO2, 30 degrees C), peak tetanic force was unchanged, but the rise and relaxation times of tetani were increased by 27 and 112%, respectively. In both muscles greater decreases in tetanic force were observed during repetitive or ischemic stimulation, which resulted in intracellular pH similar to that produced by hypercapnia. Contrary to previous reports, there was no significant decrease in PCr level in either muscle type with decreased intracellular pH. In the soleus at 30 degrees C there was a significant increase in PCr level with decreased pH. PMID- 1905191 TI - Care of the gut in the surgical intensive care unit: fact or fashion? AB - The traditional approach to the care of the gastrointestinal tract in the intensive care unit has been one of neglect. However, recent evidence has linked enteric flora to the generation of clinical sepsis in the absence of other infectious foci. The role of the bowel as an efficient barrier to the invasion of its own flora is addressed in this paper. A variety of insults disrupt the integrity of the barrier function of the gut, allowing the entry of bowel organisms or endotoxins, or both, into the portal and systemic circulatory systems. In animal and early clinical studies, a number of interventions, aimed at altering the enteric flora and enhancing the bowel's barrier function, have been shown to modulate the host's resistance to different insults and may even improve clinical outcome. Such interventions include maintenance of enteral feeding, glutamine supplementation of hyperalimentation solutions and selective bacterial decontamination of the bowel. PMID- 1905192 TI - A prospective evaluation of the Button gastrostomy in children. AB - The Button gastrostomy has become popular for patients requiring long-term enteral feeding, because it is considered less irritating, more stable and more esthetically acceptable than the traditional tube gastrostomy. By a standardized questionnaire and personal interview, the authors evaluated prospectively the efficacy and complication rate in 19 children who had a Button gastrostomy inserted during a 6-month period. In 15 children the Button replaced a standard tube gastrostomy, and in 4 the Button was inserted surgically initially. Thirteen children had severe neurologic disabilities, and 6 required supplemental enteral feeding as part of the nutritional management of another chronic disease. In all 19 children, the Button was esthetically more acceptable and produced less skin irritation than the standard tube gastrostomy. All but one caregiver thought that the Button gastrostomy was preferable to a tube gastrostomy. This was especially apparent in the six neurologically normal children who were able to be more active and had an improved self-image. Cost analysis showed that, despite the higher initial cost of the Button, elimination of the need for frequent tube changes and hospital visits made it ultimately more cost effective than the standard tube gastrostomy. The authors conclude that the Button gastrostomy is a useful alternative to the standard tube gastrostomy in selected patients. Close long-term follow-up is extremely important to ensure a good result. PMID- 1905193 TI - Recurrent massive subperiosteal hemorrhage in a patient with neurofibromatosis: a case report. AB - The authors report a rare complication of neurofibromatosis, recurrent rapidly expanding massive subperiosteal hematomas, in the thigh of a 22-year-old woman. The diagnosis was confirmed by plain radiography, ultrasonography and computed tomography. The first two hematomas were drained through a longitudinal lateral incision, tightly closing the periosteum over drains and applying a compression dressing postoperatively. The third hematoma was treated expectantly. Recurrent subperiosteal hematomas may lead to the formation of huge bone cysts and grotesque limb deformity, for which amputation may be the only solution. PMID- 1905194 TI - Surgical treatment of colonic ganglioneuromatosis in neurofibromatosis. AB - Gastrointestinal involvement in neurofibromatosis occurs in three forms: neurofibromatous tumours, visceral vasculopathy and ganglioneuromatosis. A case of colonic ganglioneuromatosis is reported and six similar cases from the literature are reviewed. The clinical and pathological features of this condition are summarized and guidelines for surgical therapy formulated. Subtotal colectomy is recommended for pseudo-obstructive symptoms refractory to medical management. PMID- 1905195 TI - Influence of caffeine on development of benign and carcinomatous mammary gland tumors in female rats treated with the carcinogens 7,12-dimethylbenz(a)anthracene and N-methyl-N-nitrosourea. AB - The effect of chronic caffeine consumption (500 mg/liter of drinking water) on the initiation and promotion stages of 7,12-dimethylbenz(a)anthracene (DMBA) (a low dose, 0.5 mg/100 g body weight, i.v.) and N-methyl-N-nitrosourea (MNU) (a standard dose, 2.5 mg/100 g body weight, i.v.) induced mammary gland tumorigenesis in female Sprague-Dawley rats was determined. In the initiation studies, caffeine was administered for 30 days prior to and for 3-4 days after carcinogen treatment (carcinogens administered at 55-57 days of age); in the promotion studies, caffeine was administered beginning 3-4 days after carcinogen treatment and until experiment termination (DMBA study and MNU study, 48 and 26 weeks after carcinogen treatment, respectively). In the DMBA study, there were 62 73 rats/group, in the MNU study, 40 rats/group. Eighty-nine % of the mammary tumors induced by DMBA were benign (adenomas, fibroadenomas, often with cystic secretory activity), 11% were carcinomas (intraductal and invasive); virtually all of the MNU-induced mammary tumors were carcinomas (approximately 99%). Caffeine consumption during the initiation stage in the DMBA-treated rats resulted in a significant decrease in the mean number of mammary carcinomas per rat (50% reduction, P less than 0.01) and mean number of benign mammary tumors per rat (28% reduction, P less than 0.05); caffeine consumption during the promotion stage significantly decreased the mean number of benign mammary tumors per rat (57% reduction, P less than 0.001) while not significantly influencing mammary carcinoma number. In contrast, caffeine consumption during either the initiation or promotion stages of MNU-treated rats did not significantly influence this tumorigenic process. The influence of caffeine on urinary and fecal excretion of tritiated DMBA and on rat mammary gland development at the time of carcinogen treatment also was determined. Slightly reduced levels of tritium in 24-h urinary samples were observed in caffeine-treated animals (P = 0.06). No significant effect of caffeine on 24- to 96-h fecal or 48- to 96-h urinary excretion of the isotope was observed. No apparent effect of caffeine on rat mammary gland development (number of ducts, degree of lobuloalveolar development) was observed. That caffeine significantly suppresses the initiation stage of DMBA-induced rat mammary gland tumorigenesis, while not influencing this stage when MNU is used as a carcinogen, suggests that caffeine acts via an alteration in carcinogen (DMBA) activation. The lack of a pronounced effect of caffeine on tritiated DMBA excretion, however, does cast some doubt on this mechanism.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1905196 TI - Effect of intraperitoneal injection volume and antibody protein dose on the pharmacokinetics of intraperitoneally administered IgG2a kappa murine monoclonal antibody in the rat. AB - The i.p. route of antibody administration offers a regional delivery advantage to the peritoneal cavity. In an effort to optimize this method of delivery, the volume of i.p. injection and total protein dose were examined for their effect on the absorption and disposition of an IgG2a kappa murine monoclonal antibody. 5G6.4, administered i.p. Normal rats (Sprague-Dawley) were given one of two protein doses (1-2 or 100 micrograms) of 125I-5G6.4 in a 2.0-ml i.p. injection volume. In both cases the same radiation dose (approximately 20 mu Ci/rat) was administered since only the tracer level (1-2 micrograms) was labeled. Hence, the 100-micrograms dose consisted of approximately 2 micrograms of labeled antibody with 98 micrograms of unlabeled antibody. In a separate experiment, two i.p. injection volumes (2.0 or 20.0 ml) of 125I-5G6.4 (approximately 20 mu Ci/rat) were administered to normal Sprague-Dawley rats. Pharmacokinetic modeling of the whole blood radioactivity levels was undertaken for both groups. The liver, kidney, muscle, lung, diaphragm, and anterior mediastinal lymph nodes were excised upon sacrifice and tissue levels at sacrifice were recorded. The volume of i.p. injection is shown to be a significant factor with respect to i.p. transport. Maximum concentration in the blood, Cmax, was reduced (P less than 0.1) and time of maximum concentration, tCmax was prolonged (P less than 0.05) from 8.4 h (in the 2-ml group) to 14.5 h (in the 20-ml group). Both contribute to a modest reduction in AUC(0----infinity) (P less than 0.15) in which AUC is the area under the concentration-time curve. The increase in blood clearance, Clb, at the higher injection volume (0.287 ml/h for the 20-ml volume and 0.194 ml/h for the 2-ml volume) is presumably due to increased diuresis resulting from autoregulation of fluid removal via lymphatic drainage. Volume of distribution, Vd, is increased since Vd and Clb are functionally proportionate and elimination is assumed constant. Tissue levels at sacrifice, except for the thyroid and anterior mediastinal lymph nodes, were the same. Mean thyroid levels were reduced in the 20-ml group (P less than 0.05) by 22.5%, likely as a result of increased diuresis. Increased nodal uptake (P less than 0.01) can be attributed to the dilution effect of the bolus injection. The rate of mass transfer is greater for the 2-ml group up to 4 h postinjection. Subsequently, the mass transfer rate is greater for the 20-ml group.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1905198 TI - Control of carcinoembryonic antigen gene family expression in a differentiating colon carcinoma cell line, Caco-2. AB - The levels of control involved in the regulation of expression of the carcinoembryonic antigen (CEA) gene family members were investigated using cultured Caco-2 cells that differentiated after confluence as characterized by the production of polarized monolayers and the subsequent appearance of domes. Three transcripts representing CEA (3.0 and 3.5 kilobases) and nonspecific cross reacting antigen (NCA) (2.6 kilobases) were detected in Northern analyses of mRNA preparations of such cells when probed with human CEA cDNA, albeit at different levels. The major CEA 3.0-kilobase transcript increased 3-fold over an 11-day culture period after confluence, whereas the NCA transcript increased 25-fold over the same time period. gamma-interferon treatment enhanced CEA mRNA levels 32 fold and NCA mRNA levels 53-fold in Caco-2 monolayers 11 days after confluence. The NCA gene thus appears to be regulated by a mechanism different from that of CEA. During gamma-interferon treatment, the normal increase in Caco-2 dome formation with time in culture was increased further by a factor of 2. Over the 13-day time span for Caco-2 cultures, CEA protein levels increased 7-fold, NCA (Mr 48,000) protein 5-fold, while gamma-interferon treatment augmented CEA 18.5 fold further and NCA 20-fold. In 2 other colon carcinoma cell lines, SW1222 and T84, which are differentiated in culture to varying degrees, little if any changes were seen in CEA and NCA mRNA and protein levels in pre- versus postconfluent cultures. Both cell lines, however, responded to gamma-interferon treatment by increases in CEA and NCA mRNA levels and, in some cases, disproportionate increases in the corresponding proteins. The lack of direct proportionality between mRNA and protein expression suggests that, as observed in human colon carcinoma and adjacent normal tissue, both transcriptional and post transcriptional control mechanisms regulate CEA gene family member expression in colon carcinoma cells. PMID- 1905197 TI - Structures of the (+)- and (-)-trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10 tetrahydrobenzo(a)pyre ne adducts to guanine-N2 in a duplex dodecamer. AB - The structures of the mirror image (+)- and (-)-trans-anti-adducts of 7,8 dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene to guanine N2 have been of great interest because the high biological activity of 7,8-dihydroxy-9,10-epoxy 7,8,9,10-tetrahydrobenzo(a)pyrene in mammalian mutagenesis and tumorigenesis has been attributed to the predominant (+)-trans-anti-adduct. We have carried out new potential energy minimization studies, involving wide-scale conformational searches on small modified DNA subunits, followed by energy-minimized build-up techniques, to generate atomic resolution views of these adducts. These energy minimized duplex dodecamers were then subjected to 100-ps molecular dynamic simulations with solvent and salt to yield animated molecular structures. The most favored computed structure for the (+)-adduct places the pyrenyl moiety in the B-DNA minor groove, with its long axis directed toward the 5' end of the modified strand, and with a pronounced bend in the helix axis. In the (-)-adduct, there are 2 favored structures. One places the pyrenyl moiety in the minor groove, whereas the other positions it in the major groove; in both cases, the pyrenyl long axis is directed more toward the 3' end of the modified strand, and with much less helix axis bend. Structures with intercalation character computed for these adducts are less preferred. The favored computed structures agree with spectroscopic data on the (+)- and (-)-trans-anti-adducts, whereas recent experimental evidence suggests that cis-adducts assume intercalation-type structures. Perhaps the conformational distinctions elucidated for the (+)- and ( )-trans anti-adducts play a role in their differential tumorigenic properties in mammalian systems. PMID- 1905199 TI - Protective effect of ICRF-187 against normal tissue injury induced by adriamycin in combination with whole body hyperthermia. AB - The use of [(+)-1,2-bis(3,5-dioxopiperazinyl-1-yl)]propane (ICRF-187) as a protective agent against normal tissue toxicity caused by combined Adriamycin (ADR) and whole body hyperthermia (WBH; 2 h at 41.5 degrees C) was assessed in a rat model. The effect of ICRF-187 on the antitumor response induced by the combination of ADR and WBH was also investigated in order to assess alterations in the therapeutic index of this combined therapeutic modality treatment. ICRF 187 significantly reduced ADR-mediated body weight loss, renal toxicity, and cardiomyopathy under both normothermic and hyperthermic conditions as shown by morphological and functional assays. ADR-induced neuropathy (seen only in normothermic rats) was also ameliorated by ICRF-187. Although this study did not show a pronounced effect of ICRF-187 on ADR-induced acute myelosuppression, ADR mediated chronic anemia, leukocytosis, and thrombocytosis were reduced by ICRF 187 in both normothermic and WBH-treated rats. The effect of ICRF-187 on antitumor response was evaluated with a tumor growth delay assay using an in vivo transplantable fibrosarcoma. ICRF-187 caused no significant change in tumor growth delay induced by either ADR alone or ADR combined with WBH. Indeed, the only complete tumor regression following treatment resulted from the combination of ICRF-187 plus ADR plus WBH. Thus, ICRF-187 significantly increases the therapeutic index of the combined modality treatment of ADR and WBH by selectively reducing normal tissue toxicity without interfering with antitumor efficacy. PMID- 1905201 TI - Cell types in the fetal pars tuberalis of the human adenohypophysis at mid gestation. AB - The pars tuberalis of the adenohypophysis was investigated in three human fetuses at mid-gestation by electron microscopy or immunohistochemistry. In addition to gonadotrophs and thyrotrophs, identified by immunohistochemistry and ultrastructural morphology, electron microscopy revealed the existence of an additional differentiated cell type closely resembling "pars tuberalis-specific" cells known from other species. The role of this cell type in the human endocrine regulation remains to be elucidated. PMID- 1905200 TI - Enkephalin-immunoreactive cells in the mesencephalic tegmentum project to the optic tectum of the teleosts Salmo gairdneri and Salmo salar. AB - Immunocytochemistry using antibodies against Met-enkephalin and Leu-enkephalin has demonstrated a group of large enkephalin-immunoreactive neurons in the nucleus of the rostral mesencephalic tegmentum (mRMT) of two teleost fish. Salmo gairdneri and Salmo salar. Injections of cobalt-lysine in the medial optic tectum retrogradely labeled the above group of tegmental neurons. Tegmental neurons were labeled only ipsilaterally to the injection site. This indicates that enkephalinergic neurons in the nRMT project to the optic tectum, and that at least some of the enkephalinergic axons observed in the optic tectum belong to a tegmen-to-tectal pathway. Comparable enkephalinergic pathways have been described in reptiles and birds, where pretectal-mesencephalic nuclei contribute to the enkephalin-containing fibers that project to the optic tectum. PMID- 1905202 TI - Effects of protopine on blood platelet aggregation. III. Effect of protopine on the metabolic system of arachidonic acid in platelets. AB - The mode of action of protopine on blood platelet aggregation was investigated in the metabolic system of arachidonic acid and in liberation of platelet activating factor using in vitro experimental models. Protopine inhibited the releases of arachidonic acid and platelet activating factor from platelet membrane phospholipids. Protopine also inhibited the conversion of prostaglandin G2 to thromboxane A2, as well as carboxyheptyl imidazole, a thromboxane synthetase inhibitor. These results indicated that protopine functions both as a phospholipase inhibitor and a thromboxane synthetase inhibitor. It is expected that protopine can be applied for treatment of thrombosis as an antiplatelet drug. PMID- 1905203 TI - [Plasma tissue-type plasminogen activator and plasminogen activator inhibitor activities and their ratio in patients with ischemic stroke associated with stagnation of blood during various stages]. AB - The studies showed that t-PA activity was elevated during the acute phase, remained elevated during the recovery stage and declined during the sequelar stage. Lowering of PAI activity was found during the acute phase, which was reversed during the recovery phase and remained significantly elevated during the sequelar stage compared with the controls (P less than 0.001), F test showed that both t-PA and PAI activities changed significantly during various stages (t-PA, P less than 0.01; PAI, P less than 0.001). Because of these changes, the ratio of PAI and t-PA fluctuated during different stages of the disease. This ratio decreased during the acute stage and came close to the normal levels during the recovery phase. The ratio, however, elevated abnormally during the sequelar stage, compared with healthy controls (P less than 0.05), In addition, the result of correlation test and linear regression analysis of serum t-PA and PAI activities in 54 cases showed a significant negative correlation (P less than 0.001) existed between t-PA and PAI activities. The balance of plasma t-PA and PAI activities have the function in maintaining the normal bloodstream in human body. In the process of disease, the abnormality of plasma t-PA and PAI activities may be the different pathological characteristics involved in this stagnation process. If coordinated with differentiation of syndrome in TCM, it may have the important significance to follow-up, and determine prognosis and early diagnosis for certain potential clinical stagnation of blood. PMID- 1905204 TI - Treatment of cutaneous leishmaniasis using a carbon dioxide laser. AB - Use of a carbon dioxide laser to vaporize the local lesions caused by cutaneous leishmaniasis is reported. A total of 108 patients have been treated in this way and followed up. The treatment reduces the management time of patients at least 1.5 times and is followed by satisfactory aesthetic outcomes. No recurrences have been observed among the 82 patients who have been followed up for 7 years. PMID- 1905205 TI - Surveillance of patients with chronic ulcerative colitis. WHO Collaborating Centre for the Prevention of Colorectal Cancer. AB - In chronic ulcerative colitis, the object of surveillance is prevention of cancer or at least prevention of death from cancer by diagnosis at an early curable stage or by detection at a pre-malignant phase. Patients must be informed about their cancer risk as well as the limitations of endoscopic surveillance and the availability of surgical alternatives. Physicians must bear in mind the risks, benefits and costs of surveillance procedures. Patients at greatest risk of cancer for whom endoscopic surveillance is warranted are those with extensive colitis of greater than 8 years duration. Colonoscopy should be performed every 1 to 2 years at which time multiple biopsies are obtained from every 10-12 cm of normal-appearing mucosa. Targeted biopsies should also be obtained from areas where the surface appears raised as a broad-based polyp, low irregular plaque or villiform elevation, or from an unusual ulcer, particularly one with raised edges, or from a stricture. Typical inflammatory polyps need not be sampled. Colectomy is recommended in the presence of multifocal high-grade dysplasia if confirmed by an experienced pathologist. The identification of a mass lesion associated with any degree of overlying dysplasia is also a generally accepted indication for colectomy, while persistent low-grade dysplasia without a mass is somewhat more controversial. Recently introduced biomarkers may replace or supplement dysplasia in surveillance programmes as well as provide new information about malignant transformation. PMID- 1905206 TI - Prevention and control of haemophilia: memorandum from a joint WHO/WFH meeting (World Federation of Haemophilia) AB - Haemophilia, the commonest hereditary bleeding disorder, arises because of the absence of, decrease in, or deficient functioning of plasma coagulation factor VIII or factor IX. With rare exceptions, exclusively males are affected. This Memorandum summarizes the discussions and recommendations for the prevention and control of haemophilia made by participants at a joint WHO/World Federation of Haemophilia Meeting, held in Geneva on 26-28 March 1990. PMID- 1905207 TI - Prevalence of infections and their risk factors in geriatric institutions: a one day multicentre survey. AB - This one-day prevalence survey of 1919 patients (74% females and 44% aged greater than or equal to 85 years) in nine geriatric hospitals, six of them located in France and three in Switzerland, indicated a high prevalence of infections in elderly institutionalized patients (infection rate: 18.7% in males and 15.4% in females). The risk factors for infection were identified and the relative risks assessed. Prevention of infections in geriatric wards should be one of the goals of every care-giver. A low rate of infection in elderly inpatients is thus likely to be associated with care of good quality. PMID- 1905208 TI - Geographical and socioeconomic factors relating to the distribution of Schistosoma mansoni infection in an urban area of north-east Brazil. AB - A study was carried out in Santo Antonio de Jesus, a town in Bahia State, north east Brazil, to determine the relationship between various biological, socioeconomic, behavioural, and geographical factors and the prevalence and intensity of Schistosoma mansoni infection. The town's population was around 45,000 and the study was targeted at all children born in 1970-71 who were living in the town at the time of the survey (August-November 1984). An extensive questionnaire was used to collect information on each child and on family and household conditions; samples of stools were also taken for examination (Kato Katz method). A survey of water snails was also carried out and information on the distribution of their breeding sites was plotted on a map of the area. The overall prevalence of S. mansoni infection was 31.0%. Several variables that reflected different aspects of the population's way of life were strongly associated with the prevalence and the intensity of infection. Some of the findings are valuable for understanding the mechanisms involved in the occurrence of schistosomiasis and its distribution in urban locations as well as for defining high-risk groups, all of which are important for planning control strategies. PMID- 1905209 TI - Urinary excretion of histamine and methylhistamine in testicular feminizing syndrome. AB - Histamine is implicated in several reproductive functions. Correlation between histamine metabolism and sex hormones has been a matter of interest for many years. Urinary histamine excretion has been studied under various experimental conditions in different species. In man it was reported, that the urinary excretion of histamine and/or methylhistamine in women was correlated to the excretion of oestrogen. Very little is known about the condition in man with intersex. The case reported here shows that histamine and methylhistamine excretion in urine in a patient with testicular feminizing syndrome is unaffected by castration. PMID- 1905210 TI - Leg ulcers in the primary antiphospholipid syndrome. Report of a case with a peculiar proliferative small vessel vasculopathy. AB - Leg ulcers are associated with antiphospholipid antibodies in patients with systemic lupus erythematosus. They may also occur in patients with primary antiphospholipid syndrome(PAPS). Histopathologic findings at the edges of the ulcers may give insight into their pathogenesis. In a patient with PAPS and a leg ulcer, a biopsy of the ulcer's edge revealed a peculiar small vessel nodular proliferation in the upper and lower dermis. There was mild mixed inflammatory infiltrate in the surrounding connective tissue, a few vessels with fibrin thrombi, and some with fibrin deposition within their walls. A review of the literature revealed similar findings in other skin ulcers associated with lupus anticoagulants. This suggests peculiar pathogenetic mechanisms that may be akin to those responsible for antiphospholipid arterial vasculopathy. PMID- 1905211 TI - Role of in-111 labeled leukocyte scintigraphy in the diagnosis of intracerebral lesions. AB - The differential diagnosis of intracerebral enhancing lesions on contrast computed tomography includes tumors, abscesses, and cerebrovascular accidents. Particularly important is the differentiation between tumor and abscess. While In 111 labeled leukocyte imaging is an accurate test for identification of foci of infection in general, the role of this procedure in the evaluation of the intracranial lesion is not well established. We undertook a retrospective review of 16 patients with contrast enhancing intracerebral lesions identified on computed tomography, who were also studied with labeled leukocyte imaging. Final diagnoses were: abscess (n = 2), primary brain tumor (n = 6), metastasis (n = 4), dermoid cyst (n = 1), and cerebral infarct (n = 3). There were two positive labeled leukocyte studies; both were cerebral abscesses. No labeled leukocyte activity was identified in any of the tumors or infarcts. We conclude that In-111 labeled leukocyte imaging is an accurate method of differentiating infectious from noninfectious causes of intracerebral lesions identified on computed tomography. PMID- 1905212 TI - Esophageal bezoars: the sucralith. PMID- 1905213 TI - Predictive value of end-tidal carbon dioxide during cardiopulmonary resuscitation. PMID- 1905214 TI - Stress-induced gastroduodenal lesions and total parenteral nutrition in critically ill patients: frequency, complications, and the value of prophylactic treatment. A prospective, randomized study. AB - OBJECTIVE: To assess the frequency, complications, and value of prophylactic treatment of stress-induced gastroduodenal lesions. DESIGNS: Patients were prospectively randomized to treatment with total parenteral nutrition, either alone, with sucralfate, or with ranitidine. SETTING: A multidisciplinary ICU from a tertiary care referral center. PATIENTS: Ninety-seven patients submitted to prolonged mechanical ventilation, with normal hepatic and renal function, in metabolic stress, and receiving total parenteral nutrition. INTERVENTIONS: On admission, we determined the Acute Physiology and Chronic Health Evaluation II score and the catabolic index score. We also performed an endoscopic examination on day 3, every 7 days subsequently, and whenever needed. Thirty patients received total parenteral nutrition alone. Twenty-four patients received total parenteral nutrition and sucralfate (1 g by nasogastric tube every 4 hrs). Nineteen patients received total parenteral nutrition and ranitidine (50 mg iv every 6 hrs). MAIN RESULTS: The overall occurrence rate of gastroduodenal mucosal damage was 29.6%. The overall frequency rate for stress ulcerations was 15.6% and was 6.2% for stress hemorrhage. There were no deaths secondary to stress hemorrhage. The difference in the frequency of stress-induced mucosal lesions and stress hemorrhage between the studied groups was not statistically significant. CONCLUSIONS: Additional prophylaxis to total parenteral nutrition in the form of sucralfate and ranitidine to prevent acute upper gastrointestinal bleeding is not required in this group of ICU patients. PMID- 1905215 TI - Components of excess ventilation in patients initiated on mechanical ventilation. AB - OBJECTIVE: To determine the causes of excess minute ventilation in patients initiated on mechanical ventilation. DESIGN: Prospective study of recently intubated, mechanically ventilated patients. SETTING: The medical ICU in a county hospital. PATIENTS: Fifty-two mechanically ventilated medical ICU patients were studied within 36 hrs of intubation. Patients were all supported with volume cycled ventilation in the assist-control mode. INTERVENTIONS: Timed expired gas collection and an arterial blood gas. MEASUREMENTS AND MAIN RESULTS: Measurements of minute ventilation and CO2 production (VCO2) were made from a timed expired gas collection. PaCO2 was sampled during the gas collection and deadspace was determined. Minute ventilation, VCO2, deadspace, and PaCO2 values in the patients were compared with predicted normal values, and excess minute ventilation due specifically to each component was calculated. Patients were separated clinically into groups: adult respiratory distress syndrome (ARDS), sepsis, obstructive lung disease, pneumonia, and drug overdose. Comparisons were then made between groups. Excess minute ventilation for the entire study population was secondary to increased deadspace (39%), low PaCO2 (36%), increased VCO2 (15%), and the interactive effect of deadspace and VCO2 (10%). VCO2 contributed little to excess minute ventilation early in respiratory failure, even in the ARDS and sepsis groups. Deadspace contributed significantly to excess minute ventilation in all groups, especially in the ARDS group, where it accounted for 53% of the excess ventilation. Low PaCO2 set-point was the predominant cause of excess minute ventilation in the sepsis group, where it contributed to 57% of their total excess minute ventilation. CONCLUSIONS: Although all groups initiated on mechanical ventilation had an excess ventilatory requirement, the contribution of individual components varied considerably between clinical groups. PMID- 1905216 TI - Modular indirect calorimeter suitable for long-term measurements in multipatient intensive care units. AB - OBJECTIVE: The construction of an indirect calorimeter capable of long-term automated sequential monitoring of multiple patients in adult and pediatric ICUs. DESIGN: A prototype system utilizing modular engineering principles, including central respiratory mass spectrometer; validation by organic solvent combustion and nitrogen dilution methods, and Tissot spirometer. SETTING: Surgical and pediatric ICUs in a tertiary care university hospital. RESULTS: When expired minute volume was measured over a range of 4 to 28 L in six intubated patients, expired minute volume measured by the prototype system demonstrated a correlation coefficient of .998 compared with simultaneous expired minute volume measured by a Tissot spirometer. Organic solvent combustion demonstrated a maximum error of 3.8% for oxygen consumption (VO2) and an average error of 1.73 +/- 1.25% (SEM). The maximum error for the respiratory quotient was 3.0%, with an average error of 1.75 +/- 1.07%. VO2 (predicted) vs. VO2 (measured) demonstrated a correlation coefficient of .997. Validation with the nitrogen dilution method over a range of FIO2 from 0.21 to 0.60 demonstrated a maximum error of 7.9%, with an average error of -1.72 +/- 1.1% (n = 51). CONCLUSIONS: Indirect calorimetry by means of a shared system for measurements in multiple patients in ICUs is feasible and cost effective utilizing modular principles and a centralized respiratory gas analyzer. PMID- 1905217 TI - BiP--a heat shock protein involved in immunoglobulin chain assembly. PMID- 1905218 TI - Search for a Drosophila-93D-like locus in Chironomus and Anopheles. AB - The results of experiments to explore the possible existence of a heat shock locus in Chironomus and Anopheles which may be comparable to the 93D heat shock locus of Drosophila, are presented. None of the heat shock loci in C. striatipennis were inducible by benzamide, colchicine, vitamin B6, thiamphenicol or a homogenate of heat shocked glands, all of which are known to selectively induce the 93D-like loci in the genus Drosophila. Benzamide also failed to induce any locus in A. stephensi. The effect of all these treatments on general transcription in Chironomus and Anopheles polytene nuclei were comparable to those known in polytene cells of Drosophila. It thus appears that a heat shock locus homologous to 93D of D. melanogaster is absent in Chironomus and Anopheles so far as inducibility of a puff by specific agents is concerned. The existence of a possible 'functional counterpart' of the 93D locus in Chironomus and Anopheles genomes cannot be eliminated. PMID- 1905219 TI - High-resolution banding in chromosomes of B lymphoblastoid cells and cultured skin fibroblasts. AB - High-resolution banded chromosomes were obtained in Epstein-Barr virus transformed lymphoblastoid cells and cultured skin fibroblasts by aphidicolin synchronization, followed by inhibition of chromosome condensation by ethidium bromide. With this method, the chromosomes of 33.3% of lymphoblastoid cells and 48.7% of skin fibroblasts were high-resolution banded, and their mitotic indices were 1.5 and 2.7 times higher than those of control cultures. PMID- 1905221 TI - Let sleeping dogs lie: role of the omentum in the ileal pouch-anal anastomosis procedure. AB - A surgical aphorism has long held that the omentum is the "watchdog of the abdomen." However, detractors believe that leaving the omentum behind after colectomy precipitates later small bowel obstruction. A retrospective comparison was made between a group of 406 patients (Group I) having omentectomy with proctocolectomy and ileoanal anastomosis and a group of 239 patients (Group II) having a similar procedure without omentectomy. Follow-up in this series of 645 patients was 4.3 +/- 2.1 years (mean +/- SEM). No difference was present in the rate of partial small bowel obstruction or complete small bowel obstruction between Group I patients (32 percent partial, 12 percent complete) and Group II patients (29 percent partial, 12 percent complete; P greater than 0.1). However, a better outcome with regard to postoperative sepsis and sepsis requiring operation was apparent in Group II patients retaining the omentum (4 percent and 3 percent, respectively) than in Group I patients (10 percent and 8 percent, respectively), in whom the omentum was removed (P less than 0.01). As this experience would support, we urge surgeons to "let sleeping dogs lie" and, when possible, retain the omentum when performing colectomy or proctocolectomy. PMID- 1905222 TI - [Structural heterochromatin in the early embryogenesis of Drosophila melanogaster]. PMID- 1905220 TI - Replication analysis of plasmid DNAs injected into Drosophila embryos. AB - From a "shotgun" collection of DNA fragments, isolated from Drosophila melanogaster, we selected sequences that function as autonomously replicating sequences (ARS) in the yeast Saccharomyces cerevisiae. To investigate the replicative potential of such sequences in Drosophila, five of these ARS elements and also the Adh gene of D. melanogaster, which has been described earlier to have ARS function in yeast, were microinjected into developing Drosophila eggs and analysed after reisolation from first instar larvae. As an assay for DNA replication, we determined the sensitivity of recovered plasmid DNA to restriction enzymes that discriminate between adenine methylation and non methylation. Within the limits of detection our results show that none of the plasmids replicated two or more rounds. However, a fraction of all injected plasmid DNAs, including vector DNA, seems to replicate once. The same result was obtained for a DNA sequence from mouse that had been reported to have replication origin function in mouse tissue culture cells. We excluded the possibility that methylation of the plasmids is the reason for their inability to replicate. These results demonstrate that homologous and heterologous DNA sequences that drive replication of plasmids in cells of other species are not sufficient to fulfil this function in Drosophila embryos. PMID- 1905223 TI - Effects of acute hypoxemia on umbilical arterial Doppler indices in a fetal ovine model. AB - Changes in umbilical arterial Doppler waveform in response to acute maternal hypoxemia were assessed in a chronic ovine model. Maternal heart rate, blood gases, fetal heart rate and umbilical arterial Doppler indices measured at baseline conditions and during periods of maternal hypoxemia were compared. The indices measured were systolic-diastolic ratio (S/D), pulsatility index (PI) and resistance index (RI). Fetal heart rate decreased (less than 80 beats/min) and umbilical arterial Doppler indices increased (P less than 0.001) during the periods of hypoxemia. Furthermore, the Doppler indices were highly but negatively correlated with alterations in the fetal heart rate (FHR) (P less than 0.001). Analysis of the Doppler waveform phase intervals revealed nearly constant systolic intervals while diastolic intervals varied inversely with the heart rate alterations. Moreover, the umbilical arterial Doppler indices, when corrected for FHR changes, were relatively unchanged from baseline measurements. This study indicates that maternal hypoxemia induced changes in the umbilical arterial Doppler indices may be primarily attributable to the changes in FHR. PMID- 1905224 TI - Thyroid vascular conductance: differential effects of elevated plasma thyrotropin (TSH) induced by treatment with thioamides or TSH-releasing hormone. AB - We have reported previously that thyroid gland blood flow, expressed as vascular conductance (C) per mass, is decreased at very low and increased at very high chronic plasma TSH concentrations, but is apparently unchanged over a broad range of plasma TSH concentrations encompassing normal levels. The aim of the present study was to examine the apparently very steep dose-response relationship between elevated plasma TSH and thyroid vascular C/mass. In the first series of experiments, endogenous plasma TSH concentrations were manipulated by treating male Sprague-Dawley rats (250-280 g) for 6 days as follows: 1) controls (0.5 ml saline/day, ip), 2) propylthiouracil injections (2.0 mg PTU/day, ip), 3) PTU plus partial thyroid hormone replacement (2.0 mg PTU/day and 0.3-0.9 microgram T4 plus 0.075-0.225 microgram T3/100 g.day via continuous sc infusion), or 4) TRH (9-1200 micrograms TRH/100 g.day via continuous iv infusion). The vascular C values of the thyroid gland, salivary gland, kidney, and pancreas were determined using the reference sample version of the radioactive microsphere technique. PTU treatment led to the expected hypothyroidism, increased plasma TSH concentrations (959 +/- 66 vs. 154 +/- 22 ng/dl), increased thyroid weight (9.19 +/- 0.36 vs. 4.60 +/- 0.15 mg/100 g), and increased thyroid vascular C/mass (495 +/- 51 vs. 127 +/- 20 microliters/mm Hg.g/min). PTU-treated rats receiving partial thyroid hormone replacement demonstrated a dose-related suppression of plasma TSH, thyroid weight, and thyroid vascular C. Although, TRH treatments resulted in increased plasma TSH concentrations (e.g. 1200 micrograms TRH, 706 +/- 46 ng/dl) and thyroid weight (e.g. 1200 micrograms TRH, 7.45 +/- 0.41 mg/100 g), thyroid vascular C per tissue mass was not significantly increased after any TRH treatment (e.g. 1200 micrograms TRH, 166 +/- 19 microliters/mm Hg.g/min). Thus, at similarly elevated plasma TSH concentrations, the thyroid vascular C/mass of PTU- and TRH-treated rats constituted separate populations. Both PTU- and TRH induced thyroid growth were accompanied by similar alterations in thyroid gland morphology (i.e. increased cellular mass with little change in the total amount of colloid). To investigate the mechanisms involved, groups of rats were treated for 6 days as follows: 1) control, 2) PTU or methimazole (25 mg MMI/day, ip), 3) PTU or MMI plus thyroid hormone replacement (1.2 micrograms T4 plus 0.3 microgram T3/d.100 g), 4) TRH (12 micrograms/100 g.day), and 5) PTU or MMI, thyroid hormones, and TRH.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1905225 TI - The function but not the expression of rat liver inhibitory guanine nucleotide binding protein is altered in streptozotocin-induced diabetes. AB - Adenylate cyclase activity was examined as a measure of inhibitory guanine nucleotide binding protein (Gi) function in liver plasma membranes from rats made chemically diabetic by streptozotocin (STZ) treatment. Clonidine activation of the alpha 2 adrenergic receptor, which activates Gi, inhibited forskolin- stimulated adenylate cyclase activity in control membranes. However, there was no effect on adenylate cyclase activity in membranes from STZ diabetic animals. Also, a polyclonal antipeptide antibody was raised to a highly conserved segment of the Gi alpha 2 subunit. This antibody specifically recognizes a 41 kilodalton protein, is blocked by an excess of peptide, does not recognize the alpha-subunit of transducin, and immunoprecipitates a 41 kilodalton protein which was ADP ribosylated by pertussis toxin. Immunoblots using this antibody detect no difference between normal and STZ diabetic animals in the level of liver plasma membrane Gi expression. Therefore, STZ-induced diabetes altered the function of Gi but had no effect on Gi expression. PMID- 1905226 TI - Effects of interleukin-6, interleukin-2, and tumor necrosis factor alpha on transferrin release from Sertoli cells in culture. AB - Recent studies demonstrate that several cytokines are potent modulators of steroid release from the testis. In an attempt to determine whether these agents may influence other types of secreted substances, we used plaque assays to measure the effect of interleukin-6 (IL-6), interleukin-2 (IL-2), and tumor necrosis factor alpha on transferrin (TF) release from Sertoli cells in culture. Because Sertoli cells from different parts of the tubule respond differently to modulatory factors, we used cultures obtained by microdissection from stages III V, VII, IX-XI, and XIII of the cycle of the seminiferous epithelium. Our results revealed that each agent increased the rate of TF plaque formation from cultures of IX-XI, and XIII staged segments but not from those staged III-V and VII. Moreover, IL-6, but not the other cytokines, modified the response of Sertoli cells to another regulator, FSH. This was evidenced by our findings that pretreatment with IL-6 for 1 h resulted in FSH-induced increases in the rate of plaque formation for cells from IX-XI segments, in addition to those segments which are normally responsive without pretreatment (III-V and VII segments). Further experiments revealed that IL-6 also had a chronic influence on the proportion of TF secretors present in certain staged cultures. Treatment for 24 h with IL-6 markedly reduced the percentage of TF secretors in cultures from stage XIII segments and resulted in a slight increase in TF cells for stage VII cultures. However, no chronic influences in TF secretors were detected with either IL-2 or tumor necrosis factor alpha treatment. Our results demonstrate very clearly that certain cytokines acting in a stage specific manner have acute and/or chronic influences on the release of TF from Sertoli cells. These findings, when viewed in light of reports of the presence of these factors in the testis, suggest strongly that cytokines or cytokine-like substances, by modulating the release of Sertoli cell substances, may play an important role in testis function. PMID- 1905227 TI - Actions of the testicular paracrine factor (P-Mod-S) on Sertoli cell transferrin secretion throughout pubertal development. AB - Peritubular cells that surround the seminiferous tubules have been shown to produce a paracrine factor, termed P-Mod-S, that has dramatic effects on Sertoli cell function in vitro and is postulated to be important in the control of testicular function. The current study was designed to determine whether P-Mod-S has the ability to regulate Sertoli cell function during pubertal development. Sertoli cells were isolated from 10-, 20-, and 35-day-old rats which correspond to the prepubertal, mid-pubertal, and late pubertal stages of development. Histochemical analysis of cultured cells isolated from each age group was performed to establish the purity of the cell populations used. Testicular transferrin production by Sertoli cells was used as a marker of cellular differentiation. Basal production of transferrin by the cultured cells was found to increase during the pubertal period. P-Mod-S stimulated transferrin production by Sertoli cells isolated from 10-, 20-, and 35-day-old rats. FSH appears to enhance the ability of Sertoli cells to respond to P-Mod-S with cells obtained from 10-day-old rats. Sertoli cells from 35-day-old rats were nonresponsive to regulatory agents such as FSH. P-Mod-S alone, however, significantly stimulated transferrin production by Sertoli cells from this more adult stage of development. P-Mod-S was the only individual regulatory agent tested that could stimulate transferrin production by Sertoli cells from 35-day-old rats. Results indicate that P-Mod-S has the ability to regulate Sertoli cell function throughout pubertal development. Observations suggest that P-Mod-S and FSH may act together in the prepubertal testis to promote Sertoli cell differentiation and that P-Mod-S may act in the adult testis to maintain optimal Sertoli cell function and differentiation. PMID- 1905228 TI - Evidence that inhibin plays a major role in the regulation of follicle stimulating hormone secretion in the fully adult male rhesus monkey (Macaca mulatta). AB - In the juvenile male rhesus monkey in which an adult-like pattern of endocrine activity in the pituitary-testicular axis is imposed by pulsatile stimulation with exogenous GnRH, administration of inhibin antiserum elicits a marked and selective hypersecretion of FSH. This finding suggests that in the monkey, testicular inhibin plays a major role in the postpubertal regulation of this gonadotropin. The purpose of the present study was to confirm this view more directly. To this end, 10 adult male rhesus monkeys were implanted with indwelling venous catheters and housed in specialized cages that permit continuous access to the venous circulation with minimal restraint and without tranquilization. Six of the males received a continuous infusion of an ovine antiserum to the alpha-subunit of human inhibin (iv bolus injection of 2.22 ml/kg BW, followed by a continuous infusion of serum at 0.62 ml/kg BW.24 h), and 4 animals received a similar infusion of control ovine immune serum. The duration of the infusion of the inhibin antiserum ranged from 2.5-7.5 days, and that for the control serum was 7.5 days. The FSH response to immunoneutralization of circulating inhibin was determined by measuring concentrations of this gonadotropin in sequential plasma samples collected between 1900-2300 h on the day before initiation of the anti-serum infusion and, depending on the duration of the infusion, on days 0.5, 1.5, 2.5, 4.5, and 6.5 of antiserum administration. In 5 of the 6 animals that received the inhibin antiserum, a progressive hypersecretion of FSH was observed during the initial 2.5 days of the infusion. This increase in circulating FSH concentration, which reached, by day 2.5 of treatment, a value 2- to 3-fold greater (P less than 0.05) than the pretreatment control level, was not associated with changes in either LH or testosterone levels. Continuation of the infusion of the inhibin antiserum beyond 2.5 days invariably resulted in a marked decline in LH and testosterone secretion, suggesting that the hypophysiotropic drive to the pituitary-testicular axis may have been compromised, presumably by a mechanism related to the infusion of heterologous serum. Infusion of the control immune serum for 2.5 days was not associated with an elevation of circulating FSH concentrations, and changes in circulating concentrations of plasma LH and testosterone were, as expected, unremarkable. Continuation of the infusion of control serum, like that of antiserum, generally resulted in a temporary but precipitous decline in LH and testosterone secretion.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1905229 TI - Fura-2 imaging of thyrotropin-releasing hormone and dopamine effects on calcium homeostasis of bovine lactotrophs. AB - Dual wavelength digital imaging microscopy to detect fura-2 has been employed to characterize in normal bovine PRL-secreting cells the effects of TRH and dopamine on the intracellular ionized calcium concentration [( Ca2+]i). Concentrations of TRH greater than 10 nM caused a rapid but transient increase in [Ca2+]i, arising mainly from intracellular calcium stores, since it was unaffected by lowering extracellular calcium with EGTA or blocking calcium channels with Co2+. The threshold for TRH action was close to 0.1 nM. TRH action was dose dependent, with lower concentrations (less than 1-10 nM) slowing the time to peak [Ca2+]i response. The TRH-induced [Ca2+]i rise had a Q10 of about 2. TRH caused multiple transient increases in [Ca2+]i, but a recovery time of 10-15 min was required for full restoration of the TRH-induced response. In some cells the [Ca2+]i response to TRH was polarized to one region of the cell, suggesting the following possibilities, none of them exclusive: 1) Ca2+ release sites may be localized within the cell; or 2) an efficient local mechanism exists for lowering Ca2+ once it is liberated inside the cells; or 3) barriers may exist to diffusion of Ca2+ released within the cell. Extracellular application of Co2+, Mn2+, and EGTA under basal conditions resulted in lowering of [Ca2+]i within seconds, consistent with tonic Ca2+ influx under resting conditions which could contribute to the basal release of hormone. Dopamine, a PRL release-inhibiting factor, also lowered [Ca2+]i under basal conditions. However, the [Ca2+]i response of lactotrophs to TRH was unaffected by dopamine. This suggests that dopamine and TRH act via separate intracellular pathways to modulate hormone secretion. Applications of forskolin preceding the TRH-induced transient rise in [Ca2+]i resulted in a prolonged plateau rise in [Ca2+]i. This was mainly due to increased influx of Ca2+ since addition of Co2+ or EGTA-containing or Ca(2+)-free medium during this phase of response lowered the plateau concentration of [Ca2+]i. PMID- 1905230 TI - Up-regulation of vinculin expression in 3T3 preadipose cells by growth hormone. AB - In an effort to define biochemical events relevant to the adipogenic action of GH, the effect of GH on expression of the cytoskeletal element vinculin was studied in 3T3-F442A preadipose cells. Results from Western blotting indicated that in serum-free medium 2 nM met-hGH induced an approximately 100% increase in vinculin expression relative to that in cells maintained in serum-free medium alone. GH-elicited alterations in vinculin expression were dose dependent. GH treatment elevated levels of tubulin to a lesser extent, whereas actin expression was unaffected by GH. Immunoprecipitation experiments revealed that GH treatment promoted a 200% increase in vinculin synthesis on day 4 relative to that in control cells. GH had no effect on phosphorylation of vinculin in 3T3-F442A cells. Based on Northern blotting, we noted that GH induced approximately a 200% increase in levels of vinculin mRNA on day 4. GH responsiveness as well as levels of vinculin were similar in 3T3-GI-16 (a highly adipogenic subclone of the 3T3 F442A cell) and 3T3-F442A cells. The GH-dependent increase in vinculin protein expression was not observed in nonadipogenic 3T3-C2 cells, suggesting that this effect of GH was related to the program of differentiation. Interestingly, levels of vinculin in nontreated 3T3-C2 cells were approximately 10-fold lower than levels in 3T3-F442A cells. GH-mediated alterations in vinculin expression in 3T3 F442A cells were abolished by treatment with fetal bovine serum, a potent mitogen. Our data indicate that increased expression of vinculin is a component of the GH-induced portion of the adipose differentiation program. PMID- 1905231 TI - Protrh peptides are synthesized and secreted by anterior pituitary cells in long term culture. AB - The expression of two ProTRH derived peptides, thyrotropin--releasing hormone (TRH) and PrePro-TRH25-50 (PYE27) was studied in anterior pituitary (AP) cells cultured in monolayer for up to 21 days. TRH levels in extracted cells rose from undetectable at 3 days to 267 +/- 22.5 fmol/well (p less than 0.01) at 21 days in culture. When AP tissue was extracted without dissociation or culture TRH was undetectable. The molar ratio of TRH/PYE27 was approximately 5:1 as predicted by the structure of PreProTRH. Extracts of cultured AP cells coeluted with TRH and PYE27 standards when subjected to HPLC analysis. Basal TRH secretion was 13.2 +/- 1.8 fmol/well/30 min at 18 days in culture; depolarizing concentrations of K+ (55 mM) caused a 2.2 fold (p less than 0.01) Ca++ dependent increase in TRH release. Immunostaining for PYE27 was found in approximately 10% of the cell population. Our results suggest that authentic ProTRH peptides are synthesized by AP cells in long term culture but not in situ. While the mechanism of activation of the PreProTRH gene needs to be elucidated we propose that TRH and/or other ProTRH derived peptides may exert paracrine effects on AP function. PMID- 1905233 TI - Acute and chronic effects of renin inhibitor GR70982 in the conscious marmoset. AB - The effects on plasma renin activity (PRA), mean arterial blood pressure (MABP) and heart rate (HR) of GR70982, a low molecular weight inhibitor of human renin, were studied in conscious marmosets. In vitro, GR70982 is a potent and selective inhibitor of human plasma renin (concentration producing 50% inhibition (IC50): human renin = 6.9 x 10(-9) M; porcine pepsin and bovine cathepin D = greater than 10(-3) M). In normotensive marmosets, i.v. GR70982 (0.001-0.1 mg kg-1) produced a dose-related inhibition of PRA. Larger oral doses (0.2, 1 and 5 mg kg-1) were required to achieve similar effects. In renin-dependent hypertensive marmosets, i.v. GR70982 (0.01 and 0.5 mg kg-1) produced dose-related decreases in MABP (-12 and -18 mm Hg) and PRA (-93 and -100%), with only minimal effects on HR. A 7-day continuous i.v. infusion of GR70982 (0.36 mg kg-1 day-1) in sodium-deplete marmosets produced a gradual decrease in MABP (-17 mm Hg at day 7, cf. control), accompanied by an inhibition of PRA (approximately 75%) and minimal HR effects. PMID- 1905232 TI - Caldesmon: a bifunctional (calmodulin and actin) binding protein which regulates stimulated gonadotropin release. AB - Calmodulin (CaM) serves as an intracellular Ca2+ receptor in the gonadotrope and appears to mediate GnRH-stimulated gonadotropin release. Recently we have specifically identified three CaM binding proteins of the gonadotrope as calcineurin, caldesmon, and spectrin. Caldesmon (identified by seven polyclonal and a monoclonal antibody, as well as by functional characteristics) appears to be a CaM-regulated, F-actin binding, protein. This 84,000 mol wt component (CaD84) is heat stable and cosediments with F-actin in the absence of Ca2+. In the presence of Ca2+ (greater than 1 microM) this protein disassociates from F actin and reassociates with calmodulin. We have prepared an antibody which blocks the caldesmon-actin interaction. In the present study, we have loaded this antibody into cells to prevent the (re-)association of caldesmon with F-actin. This treatment synergistically augments the ability of GnRH and other secretogogues (maitotoxin, phorbol myristyl acetate) to stimulate gonadotropin release from the pituitary. This finding, along with the previous observations that GnRH provokes a sufficient rise in intracellular Ca2+ to allow CaM to redistribute and bind proteins which it regulates, suggests a role for caldesmon in GnRH-stimulated gonadotropin release from the pituitary. PMID- 1905234 TI - Beta-endorphin C-terminal peptide evokes arachidonic acid release from cortical neurones. AB - The release of free [3H]arachidonic acid and its metabolites (AAM) from mouse embryo cortical neurones cultured in serum-free medium stimulated by beta endorphin C-terminal dipeptide (glycl-L-glutamine, Gly-Gln) was investigated. Gly Gln but not the related dipeptide, glycyl-glutamic acid, caused a 2-fold elevation of AAM release which was blocked in the absence of extracellular calcium, in the presence of 5 mM magnesium and by the phospholipase A2 (PLA2) inhibitor, mepacrine. Other proopiomelanocortin (POMC) peptides did not elicit AAM release. The response to Gly-Gln was unaffected by D-amino-2-phospho-5 valeric acid (AP5) and 7-chlorokynurenic acid (7-ClKY), antagonists respectively at the ligand and allosteric glycine binding sites of the NMDA glutamate receptor subtype. However, it was inhibited in a dose-dependent manner by antagonists at the phencyclidine (PCP) and sigma sites. The results suggest that Gly-Gln causes AAM release by activating PLA2 through the mediation of a PCP/sigma-like receptor. PMID- 1905235 TI - Method of removal of aortic endothelium affects arachidonic acid metabolism and vascular reactivity. AB - To assess endothelium-dependent responses of blood vessels in vitro, endothelial cells are removed by a variety of mechanical means. We sought to determine if the method of removal of the endothelium affected arachidonic acid metabolism and vascular reactivity of isolated strips of rabbit aorta. Thoracic aorta of New Zealand White rabbits were excised and sectioned into strips with a sharp razor blade. The luminal surface of the vessel was then gently stroked (denuded-1) or forcefully rubbed (denuded-2) with a moist cotton swab. Vessels were then either fixed in 3% glutaraldehyde and processed for electron microscopy, incubated with [14C]arachidonic acid and 20 microM A23187 for determination of arachidonic acid metabolism, incubated with 20 microM A23187 for measurement of endogenous release of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) and 12 hydroxyeicosatetraenoic acid (12-HETE) by specific radioimmunoassays, or suspended in an organ chamber filled with Krebs bicarbonate solution for vascular reactivity experiments. Electron micrographs showed that denuded-1 vessels lacked an endothelial cell layer and had slight degeneration of the smooth muscle cells. Additionally, these vessels had a diminished capacity to produce 6-keto-PGF1 alpha as compared to control vessels (214 +/- 25 vs. 360 +/- 36 pg/mg of tissue, P less than 0.05). Denuded-2 vessels contained severe degeneration and rupture of smooth muscle cells in addition to the loss of the endothelial cell layer. While the 6-keto-PGF1 alpha concentration (168 +/- 23 pg/mg) was less in denuded-2 vessels, HPLC indicated that the production of [14C]12-HETE was markedly increased in these vessels as compared to control or denuded-1 vessels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1905236 TI - Serotonin-induced renin release in the dog kidney. AB - The effect of serotonin (5-HT) on renin release was examined in denervated kidney of the pentobarbital-anesthetized dog. The intrarenal arterial infusion of a large dose of 5-HT (1 micrograms/kg per min) increased the renin secretion rate with an initial decrease and a subsequent increase in renal blood flow. Systemic blood pressure or heart rate was unaffected. The renin release induced by 5-HT was suppressed during intrarenal arterial infusion of a 5-HT1 and 5-HT2 antagonist, methysergide (30 micrograms/kg per min), or a selective 5-HT2 antagonist, ketanserin (3 micrograms/kg per min). A cyclooxygenase inhibitor, indomethacin (5 mg/kg i.v.), also suppressed the 5-HT-induced renin release. These results suggest that stimulation of renal 5-HT receptors, probably of the 5 HT2 type, can induce renin release from the dog kidney, which may be dependent on renal prostaglandin production. The present results, however, do not allow us to conclude that the renal 5-HT receptors play a physiological role in the control of renin release. PMID- 1905237 TI - Lack of chondrogenic expression in mouse limb bud micromass cultures exposed to exogenous beta galactosidase or N-acetyl-beta-glucosaminidase. AB - The effect of two exoglycosidases, beta-galactosidase and N-acetyl-beta glucosaminidase (GlcNAc-ase) on chondrogenic expression of stage 19 mouse limb bud micromass cultures was investigated. Chondrogenic expression was monitored by Alcian blue staining and immunofluorescent localization of cartilage-specific proteoglycan and type II collagen. Chondrogenesis was inhibited by exposure to 0.1 U/ml beta-galactosidase or 0.025 U/ml GlcNAc-ase for 24 h or longer in culture. The effect of both enzymes was concentration and time dependent. Exoglycosidic hydrolysis of galactose or N-acetylglucosamine was substantiated by treatment with HRP-conjugated peanut agglutinin and succinylated wheat germ agglutinin, respectively. Cells treated with beta-galactosidase appeared to be flattened with a stellate morphology, whereas GlcNAc-ase-treated cells were bipolar forming ridge-like mounds that had a directional orientation. The antichondrogenic effect was not alleviated when the cells were induced to assume a spherical shape upon treatment with cytochalasin D. DNA measurements indicated that the lack of chondrogenic expression was not related to cell attachment or cell proliferation. These data support the hypothesis that the expression of specific terminal sugars on cell surface glycoconjugates of limb bud cells represents an important component of the chondrogenic process. PMID- 1905238 TI - Expression of c-fos and c-myc in Raji Burkitt's lymphoma cells during the progression of DMSO-induced G1 cells into S phase. AB - Using flow cytometry, we have recently found that dimethyl sulfoxide (DMSO) reversibly induces G1-arrest in the cell cycle of human lymphoid cell lines such as Raji, Akata, and Molt-4. Here we investigated c-fos and c-myc expression in Raji Burkitt's lymphoma cells at DMSO-induced G1 arrest and after release from DMSO. A small but significant accumulation of c-fos mRNA was observed in G1 arrested Raji cells after treatment with 1.5% DMSO for 96 h. When G1-arrested Raji cells were transferred to DMSO-free medium, a transient increase in c-fos transcripts was detected 30-60 min after the release. The steady state level of c myc transcripts in G1-arrested Raji cells was found to be one-third that in the log-phase cells. After removal of DMSO, the level of c-myc mRNA was restored and reached a maximum at 4.5-6 h. Immunoblot analysis with a monoclonal antibody against human c-myc protein indicated that c-myc protein in the G1-arrested cells was decreased less than one-tenth that in the log-phase cells. The level of c-myc protein gradually increased after the release from DMSO and reached a maximum at 6-9 h. PMID- 1905239 TI - DNA cruciforms and the nuclear supporting structure. AB - Cruciforms have been suggested as potential recognition structures at or near origins of DNA replication in eukaryotic cells. Monoclonal antibodies with structural specificity for DNA cruciforms have been produced (Frappier et al. J. Mol. Biol. 193, 751, 1987). The effect of these antibodies, when introduced into permeabilized cells, was to increase overall DNA synthesis and relative copy number of genes (Zannis-Hadjopoulos et al. EMBO J. 7, 1837, 1988); this was interpreted to be a consequence of antibody stabilization of the cruciforms located at or near replication origins resulting in multiple initiations of DNA replication at a single site. Fluorescent labeling of nuclei with anti-cruciform antibodies produces a nonuniform pattern of fluorescence in cells arrested at the G1/S boundary which then changes with progression through S-phase (Ward et al. Exp. Cell Res. 188, 235, 1990). In order to determine the relationship of cruciform distribution in DNA with the nuclear matrix/chromosomal scaffold, we assessed the susceptibility of DNA containing cruciforms to digestion with DNase I. The majority of the cruciforms detectable at G1/S and throughout the nucleus are readily digested by DNase, suggesting that cruciform structures may not be intimately associated with matrix proteins. The fraction that is resistant to DNase I appears associated with nuclear membrane and the nucleolus. No cruciforms could be detected in metaphase chromosomes; cruciforms either are not present or are inaccessible--buried in the scaffold. The absence of cruciforms from metaphase chromosomes would be consistent with the viewpoint that the cruciform in vivo is a transient structure dependent upon and interacting with proteins essential for replication or transcription. PMID- 1905240 TI - Regulation of immunity in Trypanosoma cruzi infection. AB - Immunity to T. cruzi is complex, involving among other components, antibody production, CD4+ helper cells, CD8+ T cells as both regulators and effectors of immunity, and possibly, double-negative T cells. In addition, several of these components have been implicated in pathogenesis in the chronic infection. Although the immunosuppression observed in the infection seems quite severe, it also appears to provide for a sufficient level of immune responsiveness to control the infection in most hosts. At the same time, immunosuppression may provide the regulatory control necessary to prevent massive chronic pathogenesis in all hosts. Continued study of the relative roles of lymphocyte populations and the products they secrete in immunity and pathogenesis may provide the understanding necessary to enhance immunity to T. cruzi without the feared consequence of increased pathogenesis. PMID- 1905241 TI - Purification and characterization of 3-hydroxymethylglutaryl-coenzyme A reductase of Schistosoma mansoni: regulation of parasite enzyme activity differs from mammalian host. AB - The enzyme 3-hydroxymethylglutaryl-CoA (HMG-CoA) reductase plays a critical role in regulating the production of cholesterol, dolichols, and ubiquinones in mammals. The inhibition of this enzyme in Schistosoma mansoni is accompanied by a cessation of egg production by the female parasite and a reduced ability of the parasite to properly glycoslyate their proteins. Furthermore, we recently demonstrated that mevinolin, if given continuously over a period of 10-14 days, is a potent antischistosomal drug. In this paper, we describe the properties of purified HMG-CoA reductase from S. mansoni. Using affinity chromatography, we were able to obtain a 417-fold purification of the enzyme which had Km values similar to the rat enzyme for HMG-CoA and NADPH. The Ki value for mevinolin, a potent and selective inhibitor of the rat reductase (Ki = 0.6 nM), was significantly higher (Ki = 46 nM) for the schistosome enzyme. SDS-PAGE and HPLC of the purified enzyme resulted in the appearance of a single protein, which had a molecular weight (66,000) in the range reported for the rat enzyme. Parasite reductase activity, unlike that of its host, did not display a circadian rhythm. Furthermore, agents which elevate (cholestyramine) or decrease (cholesterol) mammalian reductase activity had no effect on the parasite enzyme. Our results suggest that the mechanism which regulates production of the parasite's enzyme may differ from its mammalian host. PMID- 1905242 TI - Cell cycle-dependent biosynthesis of Plasmodium falciparum DNA polymerase-alpha. AB - The DNA polymerase-alpha of Plasmodium falciparum was characterized according to aphidicolin sensitivity and immunological reactivity with monoclonal anti-sera against human DNA polymerase-alpha. Two major (105 and 72 kDa) and two minor (180 and 130 kDa) catalytic subunits of P. falciparum DNA polymerase-alpha were detected on activity gels. Activity gels did not indicate the presence of a DNA polymerase-beta in P. falciparum. Metabolically labeled polypeptides at 180, 105, 72, and 52 kDa were immunoprecipitated from Plasmodium nuclear extracts with the anti-KB cell DNA polymerase-alpha monoclonal antibody and, by size, correspond to the major subunits of mammalian DNA polymerase-alpha. The monoclonal antibody also neutralized Plasmodium DNA polymerase activity. Plasmodium DNA polymerase was synthesized predominantly at an early schizont stage at which time the parasite began to synthesize its DNA and multiply. No evidence for phosphorylation of the major catalytic subunit was obtained. Plasmodium growth, DNA synthesis, and DNA polymerase activity were inhibited significantly in parallel by aphidicolin. These results suggest that P. falciparum has a typical eukaryotic DNA polymerase-alpha and that regulation of its activity appears to be at the transcriptional level. PMID- 1905243 TI - [The role of prostaglandins in the development of cardio- and hemodynamic disorders in postischemic shock]. AB - Experiments on anaesthetized dogs have shown, that reperfusion of ischemized tissues is accompanied by significant increase in thromboxane A2 (Tx A2) and prostacyclin (PG I2) blood level and by development of pronounced cardiovascular insufficiency. Preliminary blockade of prostaglandins biosynthesis prevent an increase of TbA2 and PG12 blood level, postreperfusion disturbances of central and regional circulation develop later and are less pronounced. Therefore, endogenic prostaglandins take part in the development of post ischemic shock reaction, influencing chiefly the venous vessels and blood return to heart. PMID- 1905244 TI - [Factors in the development of arterial hypoxemia in middle-aged and elderly people]. AB - Partial pressure of oxygen and carbon dioxide in alveolar air and arterial blood, lung diffusion capacity and its components, ventilation parameters, ventilation perfusion ratio were determined in healthy people aged 60-89 (45 subjects) and aged 20-31 (19 subjects, controls). In elderly and old people PO2 in arterial blood was found to decrease with increasing alveolar-arterial PO2 gradient. In other words, arterial hypoxemia was determined by the disturbance in gas exchange between alveolar air and blood of lung capillaries. The diffusion capacity of lung decreased at the expense of membrane factor. Its age-related dynamics was mainly due to a decrease in the pulmonary diffusion surface occurring because of improper coordination of ventilation and perfusion in the lungs. The discrepancy of pulmonary ventilation and perfusion proved to be the leading factor of arterial hypoxemia in late ontogenesis. PMID- 1905245 TI - Alterations of biochemical and biomechanical properties of rat tail tendons caused by non-enzymatic glycation and their inhibition by dibasic amino acids arginine and lysine. AB - The influence of dibasic amino acids arginine and lysine on non-enzymatic glycation of tail tendon fibers from old (900-day-old) and young (61-day-old) rats was investigated in vitro. The biomechanical changes in tendon fibers of young rats after an incubation interval of 7 or 14 days in a glucose solution were abolished by the addition of arginine or lysine (molar ratio amino acid:glucose 1:10). Glucose incorporation into rat tail tendon fibers as well as Amadori product formation was decreased significantly in the presence of the amino acids. The inhibitory effect of arginine was further confirmed by measurement of the amount of ketoamine formed during the glycation reaction using soluble albumin as a protein target. The effective inhibition of non-enzymatic glycation by arginine or lysine suggests their potential use in vivo as a means of controlling protein over-glycation. PMID- 1905246 TI - Radioimmunoassay for the determination of glycated haemoglobin. AB - A competitive radioimmunoassay for the quantitative determination of glycated haemoglobin was developed. The antiserum, obtained by immunizing guinea pigs with reduced glycated human albumin, was capable of identifying and quantitating the glucitollysine residues of glycated Hb after reduction with sodium borohydride. To simplify the sample preparation we introduced trichloroacetic acid precipitation to remove unreacted sodium borohydride instead of using dialysis or gel filtration. Using this procedure, our radioimmunoassay became relatively simple and provided satisfactory within- and between-run (1.3-2.8% and 1.9-5.4% coefficient of variation, respectively). The radioimmunoassay method was compared to the measurement of HbAlc by high performance liquid chromatography which is the most widely used method for quantitating glycated Hb. For this purpose glycated Hb was measured in normal glucose tolerance, impaired glucose tolerance, and diabetes mellitus groups based on WHO criteria. Both assays were able to discriminate between the normal and diabetic groups. In addition, while the determination of glycated Hb by the radioimmunoassay method was able to clearly discriminate between the normal and impaired glucose tolerance groups, the determination of HbAlc by the high performance liquid chromatography method failed to discriminate between these two groups. Moreover, 15 of the 20 impaired glucose tolerance patients exceeded the upper normal range (mean normal values + 2 SD) in radioimmunoassay. But all 20 patients with impaired glucose tolerance were within the upper normal range in HbAlc values. These results demonstrate that the measurement of glycated Hb by radioimmunoassay is more sensitive than the measurement of HbAlc by high performance liquid chromatography since it can discriminate between the normal and impaired glucose tolerance groups. PMID- 1905247 TI - [Cytokine production by gynecologic cancers]. AB - Aggressive polychemotherapy and ultraradical surgery had had only small benefits for patients with gynaecological cancer in recent years. That is why we measured cytokines in these patients to evaluate a possible future immune therapy. To investigate the influence of gynaecological cancer on in vitro and in vivo cytokine production of peripheral mononuclear cells (PBMC) from 27 patients with mamma carcinoma and 29 patients with cervical cancer, we evaluated the production of interferon-alpha (IFN-alpha), interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha). We compared the immune function of these patients versus 20 patients who had had routine hysterectomies performed for non-malignant reasons and 20 healthy female controls. Blood for cytokine production was collected prior to surgery, for IFN-alpha-production two weeks after surgery and for all cytokines three months after surgery. Measurement of TNF-alpha-production did not differ significantly in all investigated groups. IFN-gamma-production was reduced by 50% in patients with mamma carcinoma in three months - possibly caused by chemotherapy and radiation. The amount of IFN-alpha production in cancer patients was dramatically reduced before primary therapy started. The low levels of IFN-alpha persisted for three months compared to the IFN-alpha production in non-cancer patients and healthy controls. The follow-up of patients with breast cancer undergoing chemotherapy showed a suppressive effect on immunological function in IFN-alpha. Our results demonstrate, that patients with breast cancer and cervical cancer showed a significantly reduced capacity to product IFN alpha.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1905249 TI - Na2 ethylenediaminetetraacetic acid retention enema in dogs. Biochemical and histological response. AB - 1. The use of Na2 EDTA in a per rectal lavage may facilitate cell harvesting for colonic cytology. So the effect of a Na2 EDTA 0.5% retention enema on serum electrolytes, kidney function tests and blood clotting mechanism as well as its direct effect on colonic mucosa, was evaluated in dogs. 2. The results were compared to a control study with a normal saline enema. 3. Blood samples and colonic biopsies were obtained at four time points. 4. A statistically significant decrease in serum calcium levels reaching a maximum 2 day post experiment, and increase in serum phosphorous and prolongation of prothrombin time at 2 hr post-experiment, were noted. 5. The perturbations were still within normal physiological limits for dogs, and no clinical manifestations of either hypocalcemia nor bleeding tendency occurred. 6. All other parameters evaluated did not change significantly at the examined time points. 7. Light microscopy examination of the colonic mucosa in the experimental group was not different from that of the control study. 8. Na2 EDTA may be used in retention enemas without significant clinical side effects. PMID- 1905248 TI - Observations on the pharmacology of thalicminine, an oxyaporphine alkaloid from Thalictrum isopyroides. AB - 1. The effects of the oxyaporphine alkaloid thalicminine on guinea-pig isolated ileum, trachea, aorta and pulmonary artery and on blood pressure and heart rate of anesthetized guinea-pigs were studied. 2. Thalicminine (1-300 microM) caused the relaxation of the longitudinal ileal segments. The relaxation induced by 300 microM was followed by vigorous contractions. 3. Thalicminine caused only mild relaxation of the trachea. 4. Thalicminine (0.3-300 microM) caused concentration dependent relaxation of epinephrine-precontracted aorta and main pulmonary artery. 5. Propranolol (1 microM) failed to reduce the relaxation or to affect the EC50 value of thalicminine on the ileum or the pulmonary artery. 6. Quinacrine (10 microM), on the other hand, potentiated thalicminine-induced relaxation and reduced the EC50 on the aorta and the pulmonary artery suggesting the interference of thalicminine with arachidonic acid metabolism. 7. In anesthetized animals, intravenous injections of 0.37-1.1 mg kg of thalicminine caused transient reduction of systolic and diastolic blood pressure and heart rate. Both parameters returned to their normal values in about 10 min. PMID- 1905250 TI - Nifedipine reduces the increases in cerebral blood flow during hypercapnic episodes. AB - 1. Cerebral blood flow (CBF) in the rat was monitored by a venous outflow technique with an extracorporeal circulation which allowed for continuous monitoring of flow over the several hours of the study. 2. Brief challenges with carbon dioxide (CO2) increased the CBF. 3. Nifedipine (1.00 mg/kg), a dihydropyridine calcium antagonist, attenuated the response of the animal to hypercapnia, while leaving the basal flow rate unchanged. 4. This study may have significant implications as to the effect of nifedipine on CBF. 5. Since similar results have been obtained with nifedipine in anoxia, this study suggests that the responses to anoxia and hypercapnia are interrelated and that the resulting hyperemia may be governed by the same mechanisms. PMID- 1905251 TI - Oral contraceptives stimulate the excretion of clofibric acid glucuronide in women and female rats. AB - 1. Glucuronidation of clofibric acid, the pharmacologically active form of the hypolipidemic drug clofibrate was investigated in a human population, either in vitro with liver homogenates from biopsies, or after ingestion of the drug and determination of the urinary metabolite. No difference in the glucuronidation rate according to age of the patients was observed. Bilirubin but not clofibric acid glucuronidation was significantly higher in women (106% increase), when expressed per gram of tissue. 2. The excretion of clofibryl glucuronide in women who took oral contraceptives was significantly enhanced by 25%. 3. In female rats, treatment with the contraceptive agent norethindrone also stimulated by 48% the formation of clofibrylglucuronide in liver microsomes. PMID- 1905252 TI - Possible involvement of protein kinase C in gonadotropin and growth hormone release from dispersed goldfish pituitary cells. AB - Static incubation with tumor-promoting 4 beta-phorbol esters, activators of the Ca2(+)- and phospholipid-dependent protein kinase C enzyme (PKC), caused dose dependent increases in gonadotropin (GTH) and growth hormone (GH) secretion in primary cultures of dispersed goldfish pituitary cells. The estimated half maximal effective doses (ED50) for stimulating GTH and GH release were 0.35 +/- 0.17 and 0.32 +/- 0.13 nM 12-O-tetradecanoyl phorbol 13 acetate (TPA), 3.71 +/- 1.30 and 1.37 +/- 0.76 nM 4 beta-phorbol 12,13-dibutyrate, 6.90 +/- 4.84 and 1.89 +/- 0.25 nM 4 beta-phorbol 12,13-dibenzoate, and 455 +/- 258 and 311 +/- 136 nM 4 beta-phorbol 12,13-diacetate, respectively. In contrast, treatments with up to 10 microM of the inactive 4 alpha-phorbol 12,13-didecanoate ester did not alter GTH and GH release. Additions of the synthetic diacylglycerol, dioctanoyl glycerol, also enhanced GTH and GH secretion in a dose-dependent manner and with ED50s of 1.73 +/- 0.83 and 1.73 +/- 1.19 microM, respectively. The GTH and GH responses to stimulation by TPA were attenuated by incubation with Ca2(+)-depleted medium containing EGTA or by treatment with the Ca2+ channel blocker verapamil. Coincubation with the PKC inhibitor H7 reduced the GTH and GH responses to TPA. As in previous studies, additions of salmon gonadotropin-releasing hormone (sGnRH) or chicken GnRH-II (cGnRH-II) induced GTH and GH release; these hormone responses to sGnRH and cGnRH-II were also decreased by the addition of H7. These results indicate that activation of PKC may stimulate GTH and GH release in goldfish and suggest that sGnRH and cGnRH-II actions on goldfish pituitary GTH and GH secretion are also mediated, at least partially, by PKC. PMID- 1905253 TI - Thyroid hormone regulates developmental changes in muscle during flounder metamorphosis. AB - Morphological and biochemical changes in the muscular tissue of metamorphosing flounder were studied in relation to the regulatory role of thyroid hormone. Premetamorphic larvae were reared in seawater alone or seawater containing either thyroxine (T4) or an antithyroid drug (thiourea, TU). Histological changes in the muscle were examined and biochemical changes in the muscle proteins were evaluated by SDS-PAGE and immunoblotting for troponin T (TNT). The muscle tissue of premetamorphic larvae was characterized by abundant vacuoles and basophilic sarcoplasm. In control fish, the larval muscle transformed into the adult type during metamorphic climax; the fibers were filled with abundant myofibrils and the vacuoles disappeared. Analysis by SDS-PAGE showed that the bands at 41.5, 35.5, 34.0, 33.5, 25.5, 23.0, 20.0, and 19.0 kDa clearly increased in density from the climax stage. Premetamorphic larvae possessed two immunoreactive TNT isoforms of 41.5 and 34.0 kDa, the former being predominant. At the climax stage an additional isoform appeared at 33.5 kDa, and the 34.0- and 33.5-kDa TNT became predominant. The administration of T4 precociously induced these histological and biochemical changes in the muscle tissue of flounder larvae. In contrast, TU treatment inhibited these developmental changes in the larval muscle. Our results suggest that the developmental changes in the muscular tissue of metamorphosing flounder are regulated by thyroid hormone. PMID- 1905254 TI - Genetic organization of the cSOD microregion of Drosophila melanogaster. AB - Cu/Zn superoxide dismutase (cSOD) is an important enzymatic agent of physiological defense against active oxygen species. Previously, we defined the essential biological role of cSOD in Drosophila through analysis of a cSOD null mutant. In the process of isolating this mutant, we also identified several vital genes in the chromosomal region surrounding the cSOD gene (the cSOD microregion). To further our genetic analysis of cSOD function, we have undertaken a detailed description of the cSOD microregion as defined by the breakpoints of the deficiency Df(3L)lxd9. Examination and correlation of mutations previously recovered with new X-ray induced mutations described in this paper identify a total of 12 vital genes, including cSOD, and one nonvital gene, lxd, in this region. We propose the adoption of a single genetic nomenclature for the genes of this region. Two newly generated hypomorphic alleles of cSOD are described that confer phenotypes similar to cSODn108, confirming the important physiological role of the enzyme in Drosophila. PMID- 1905255 TI - Synthesis of biologically active adenovirus preterminal protein in insect cells using a baculovirus vector. AB - A DNA fragment encoding the polyhedrin promoter of Autographa californica multiple nuclear polyhedrosis virus (AcMNPV strain) was constructed using overlapping oligodeoxyribonucleotides (oligos), which included the 5' untranslated leader sequence of the polyhedrin-encoding gene. This DNA fragment was cloned into an intermediate transfer vector (pKX105) providing a unique BamHI site for the insertion of foreign genes. The Escherichia coli lacZ gene was first cloned at the BamHI site of pKX105 and the XhoI-KpnI fragment containing the lacZ gene was transferred to another plasmid vector (pEI) consisting of flanking AcMNPV sequences (pEI-lacZ). The E. coli beta-galactosidase that was produced in the infected insect cells using the recombinant virus constituted about 10% of the total cytoplasmic proteins. The pKX105 plasmid was also modified to give rise to pTT-lacZ which consisted of the lacZ gene under the control of the Rous sarcoma virus long terminal repeat promoter to facilitate rapid screening of the baculoviral recombinants in which the gene of interest was cloned under the control of the polyhedrin promoter. The efficiency of these transfer vectors was verified by obtaining high levels of expression of the adenovirus(Ad)-encoded preterminal protein (pTP) which is involved as a protein primer in the initiation of Ad DNA replication. The baculovirus-produced pTP was immunoprecipitable using rabbit polyclonal antibodies raised against a hydrophilic domain of pTP. The pTP protein was localized in the nucleus of the infected insect cells, and was biologically active in the in vitro Ad type 2 (Ad2) replication initiation assay. PMID- 1905256 TI - Analysis of the promoter region of the housekeeping gene DmRP140 by sequence comparison of Drosophila melanogaster and Drosophila virilis. AB - To analyze the transcriptional control regions of Drosophila melanogaster household genes, we have characterized the promoter of the gene coding for the second-largest subunit of RNA polymerase II (DmRP140). Analysis of cDNA revealed that the coding region of the protein extends beyond the originally assumed transcription start point (tsp) and deduced translation start codon [Falkenburg et al., J. Mol. Biol. 195 (1987) 929-937] and that the tsp determined previously corresponds to an intron/exon boundary of an additional intron. Upstream of the polII gene we found a transcription unit that is transcribed in the opposite direction. The initiating ATGs of the two genes are only 467 nucleotides (nt) apart. The untranslated region is extremely A + T-rich (88%) but none of the transcription units is preceded by a canonical TATA element. It does not feature any other known nt sequence motifs thought to be necessary for the basic transcriptional machinery; yet, this region functions as a bidirectional promoter: a central 309-bp fragment directs transcription of a reporter gene in transiently transfected Drosophila culture cells in both orientations. The gene coding for the second-largest subunit of RNA polymerase II of Drosophila virilis (DvRP140) was isolated and partially analyzed. The gene is located on the second chromosome at 22F/23A which corresponds to the position determined for D. melanogaster.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1905257 TI - New pUC-derived cloning vectors with different selectable markers and DNA replication origins. AB - Four new Escherichia coli cloning vectors are described, pUC6S, pUC21, pUK21 and pOK12. These vectors contain a polylinker or multiple cloning site (MCS) with the recognition sequences for 28 restriction enzymes. Plasmids pUC21, pUK21, and pOK12 contain the MCS in the N-terminal end of the lacZ alpha fragment allowing blue/white screening for inserts. To potentially increase the stability of some inserts that may encode toxic proteins, the strength of the lacZ promoter present on these vectors has been reduced. Plasmids pUC6S and pUC21 carry the bla gene encoding ampicillin resistance, while pUK21 and pOK12 contain the gene encoding kanamycin resistance. Plasmid pOK12 carries the replicon from P15A, resulting in a lower copy number pUC-type vector. Plasmid pUC6S carries the ori and bla gene present on all pUC vectors, but does not contain any lac sequences. Plasmids pUC21 and pUK21 contain the M13 intergenic region allowing for the production of plasmid single-stranded DNA. To improve the yield of ss plasmid DNA, two plasmid cis-acting factors that affect yield were also examined: the effect of plasmid derived transcription across the M13 ori, and the effect of delecting the M13 minus-strand ori from the plasmid. PMID- 1905258 TI - Mutational dissociation of the positive and negative regulatory properties of the Spo0A sporulation transcription factor of Bacillus subtilis. AB - The Spo0A regulatory protein controls the onset of stationary phase and sporulation by controlling transcription in both a negative and a positive manner depending on the promoter affected. Missense mutations, e.g., spo0A9V, which result in alterations in the eleventh amino acid preceding the C terminus of the Spo0A protein, give rise to a protein active as a negative regulator of the abrB gene but unable to activate transcription of the spoIIA gene. Second-site suppressors of spo0A9V occurred within the spo0A gene at codons 162 and 174. These suppressors did not suppress a spo0F mutation, indicating that the suppressed protein still requires phosphorylation for activity. The results suggest that the C terminus of Spo0A interacts with the transcription complex to activate transcription. PMID- 1905259 TI - Production of mutant dihydrofolate reductases of Lactobacillus casei for nuclear magnetic resonance spectroscopy. AB - Seven mutations (L4P, W21L, D26E, D26N, R57H, R57K and T63Q) affecting residues of dihydrofolate reductase of Lactobacillus casei, suspected of being important in substrate, inhibitor, or cofactor binding, were made by gapped-duplex site directed mutagenesis. Expression of the L. casei dhfr gene required the removal of nucleotide sequences flanking the coding region. Temperature-inducible expression from the lambda pL promoter of plasmid pPLc28 allowed synthesis and subsequent affinity purification of five mutant proteins in amounts and purity sufficient for nuclear magnetic resonance (NMR) spectroscopic analysis (100 mg or more) from 10-liter cultures. W21L required the growth of 40-liter batches, and L4P was not found. Using a two-plasmid system with pcI857 providing lambda repressor and pMAC5-14 expressing the mutant gene, any auxotrophic strain of Escherichia coli can be used as a host, allowing isotopic labelling of each amino acid of any protein for rapid NMR peak assignment. PMID- 1905260 TI - Further characterization of the 5'-flanking DNA of the gene encoding human plasminogen activator inhibitor-1. AB - Previous nucleotide (nt) sequence analysis of the 5'-flanking DNA of the gene (PAI-1) encoding plasminogen activator inhibitor-1 revealed an extensive region of shared nt sequence identity with the 5'-flanking region of the gene (t-PA) encoding tissue-type plasminogen activator [Bosma et al., J. Biol. Chem. 263 (1988) 9129-9141]. Additional sequence (1642 bp) from the PAI-1 gene 5'-flanking region reveals that these 'PAI-1/t-PA' sequence elements share an alignment that contains a total of 575 positions. This additional PAI-1 5'-flanking sequence also contains two Alu elements that form inverted repeats. Southern-blot analysis using the PAI-1/t-PA element as a probe indicates that this element is repeated in the human genome. which supports the classification of this element as a medium reiteration frequency sequence [Jurka, Nucleic Acids Res. 18 (1990) 137 141]. PMID- 1905261 TI - Immunoglobulin complementarity-determining region grafting by recombinant polymerase chain reaction to generate humanised monoclonal antibodies. AB - We describe an approach to rapidly generate humanised monoclonal antibodies by grafting rodent complementarity-determining regions onto human immunoglobulin frameworks using recombinant polymerase chain reaction (PCR) methodology. The approach was applied to grafting a rat complementarily-determining region onto a human framework and amplifying the entire humanised heavy chain. The terminal oligodeoxyribonucleotide primers incorporated restriction sites to allow forced cloning into plasmid vectors for sequencing and expression. No nucleotide errors were introduced into the 1463-bp sequence even after sequential applications of PCR. PMID- 1905262 TI - Cloning of a gene encoding a lupus-associated human autoantibody VK region using the polymerase chain reaction and degenerate primers. AB - The variable light-chain-encoding gene of a human autoantibody secreted by a B cell hybridoma derived from a patient with systemic lupus erythematosus was amplified using the polymerase chain reaction and degenerate primers. After cloning, the nucleotide sequence of the EcoRI-HindIII region was determined. It is highly homologous to a previously described gene expressed by a human lymphoid cell line. PMID- 1905263 TI - Transcranial magnetic stimulation: influence on plasma levels of hormones of the anterior pituitary gland and of cortisol? AB - To assess possible side effects of transcranial magnetic stimulation on the release of anterior pituitary gland hormones three different examinations on 10 males were performed following a standardized protocol. Plasma levels of prolactin, FSH, LH, hGH and cortisol were determined before and after stimulation. Cortical stimulation had no specific influence on the plasma levels of the hormones examined. PMID- 1905264 TI - [In vitro effect of chlorpromazine on the mineralization of tooth germ in mice- comparison with that of retinoic acid and HEBP]. AB - Effects of chlorpromazine on the mineralization and alkaline phosphatase activity (ALP) in the tooth germ were examined and compared with those of retinoic acid and HEBP (1-hydroxyethylidene-1, 1-bisphosphonate). Mandibular first molars from 17-day-old mouse embryos were cultured with or without drugs. Calcium content and ALP in the tooth germ increased gradually from 0 to 7 days in culture, the increase of calcium being preceded by that of ALP. Retinoic acid suppressed increases of calcium and ALP in the tooth germ but not in the specimens precultured for 2 days, suggesting that retinoic acid inhibits the mineralization at an early developmental stage of the tooth. HEBP, a physiochemical inhibitor of mineralization, suppressed the increase of calcium, but significantly enhanced the increased of ALP in the tooth germ. Chlorpromazine, which has an antagonistic action towards calmodulin, also suppressed the increases of calcium and ALP in the tooth germ. Calmodulin antagonists W-7 and W-5 similarly suppressed the increases of calcium and ALP; W-5 had less effects on both calcium and ALP. These results indicate that calmodulin may be involved in the regulation of the mineralization in the tooth germ. These drugs are shown to possess different modes of inhibitory action on the mineralization. PMID- 1905265 TI - [Effect of pravastatin on hepatic cholesterol metabolism]. AB - BACKGROUND: Inhibitors of the rate-limiting enzyme of cholesterol biosynthesis, 3 hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, are now used frequently to treat hypercholesterolemia. We studied the effects of specific inhibition of cholesterol synthesis by one of these agents (pravastatin) on the hepatic metabolism of cholesterol in patients with gallstone disease who were scheduled to undergo cholecystectomy. METHODS: Ten patients were treated with pravastatin (20 mg twice a day) for three weeks before cholecystectomy; 20 patients not treated served as controls. A liver specimen was obtained from each patient at operation, and the activities of rate-determining enzymes in cholesterol metabolism as well as low-density-lipoprotein (LDL)-receptor binding activity were determined. RESULTS: Pravastatin therapy reduced plasma total cholesterol by 26 percent and LDL cholesterol by 39 percent (p less than 0.005). Serum levels of free lathosterol, a precursor of cholesterol whose concentration reflects the rate of cholesterol synthesis in vivo, decreased by 63 percent (p less than 0.005), indicating reduced de novo biosynthesis of cholesterol. Microsomal HMG CoA reductase activity, when analyzed in vitro in the absence of the inhibitor, was increased 11.8-fold (1344 +/- 311 vs. 105 +/- 14 pmol per minute per milligram of protein in the controls; p less than 0.001). The expression of LDL receptors was increased by 180 percent (p less than 0.005), whereas the activities of cholesterol 7 alpha-hydroxylase (which governs bile acid synthesis) and of acyl-coenzyme A: cholesterol O-acyltransferase (which regulates cholesterol esterification) were unaffected by treatment. CONCLUSIONS: Inhibition of hepatic HMG-CoA reductase by pravastatin results in an increased expression of hepatic LDL receptors, which explains the lowered plasma levels of LDL cholesterol. PMID- 1905267 TI - Hepatic mitochondrial membrane lipid environment and protein nutrition. AB - Effect of feeding rice diet with and without lysine and threonine supplementation on hepatic mitochondria and its inner and outer membrane proteins, enzymes and phospholipids has been studied. The exchange of phosphatidylcholine and phosphatidylethanolamine between microsomes and mitochondria has also been studied under these conditions. Deficient diet lead to significant decrease in proteins as well as activities of monoamine oxidase, succinate dehydrogenase, cytochrome a + a3 and cytochrome c in mitochondria and its inner and outer membranes. Feeding of the deficient diet also significantly reduced total phospholipids and PC in mitochondria and its outer mitochondrial membrane. In the inner mitochondrial membrane, only PE and cardiolipin were reduced. The incorporation (DPM/microgram PLP) of [methyl-3H]choline and [methyl 14C]methionine into PC of mitochondria and its outer membrane and that of 32Pi into PC and PE of outer mitochondrial membrane but only into PC of inner mitochondrial membrane were significantly reduced in the deficient group. The exchange rates of PC and PE between microsomes and mitochondria were reduced in the deficient group. Supplementation of the deficient diet with lysine and threonine profoundly improved the above biochemical lesions as compared to casein fed rats. PMID- 1905266 TI - Spatial differentiation of RH and GM haplotype frequencies in Sub-Saharan Africa and its relation to linguistic affinities. AB - This study analyzes patterns of variation in eight GM and seven Rhesus (RH) haplotypes across sub-Saharan Africa. We examine the concordance with genetic patterns of both geographic and language-family relationships by spatial analysis and ordination techniques. The genetic variation has significant spatial structure, but positive autocorrelation declines neither asymptotically nor proportionally with increasing distance. Evidently, neither isolation by distance with increasing distance. Evidently, neither isolation by distance nor clinical migration-selection models account for the observed genetic structure. Language family relationship is the best predictor of genetic relationship and may reflect historic migrations and expansions of ethnically different peoples within sub Saharan Africa. Yet the greatest part of the genetic variance remains unexplained by the models we have tested. PMID- 1905268 TI - Isolation and purification of plasminogen activator from Yoshida ascites Sarcoma of rats. AB - The plasminogen activator was purified to the extent of 150-fold from 20,000 x g supernatant of Yoshida ascites Sarcoma by ammonium sulphate precipitation at 33% saturation followed by affinity chromatography on p-aminobenzamidine-Sepharose 4B. The specific activity of the purified activator was 10,260 IU/mg expressed in terms of International units of urokinase, the known activator of plasminogen. The activator was homogeneous by polyacrylamide slab gel electrophoresis with an apparent molecular weight 75 kDa by gel filtration on Sephadex G-100. Analysis by SDS-polyacrylamide gel electrophoresis under reducing conditions, revealed the presence of two subunits of about 48 and 29 kDa. The activator displayed binding preference to fibrin and was immunologically distinguishable from urokinase, indicating that it could be of non-urokinase origin. The preparation further revealed similarity to standard tissue plasminogen activator with respect to fibrin binding and immunological cross reactivity. PMID- 1905269 TI - Studies on cytosolic superoxide dismutase from intestinal mucosa. AB - CuZn superoxide dismutase from monkey (Macaca radiata) intestinal mucosa was purified to homogenity. The enzyme showed a subunit molecular weight of 16000. The enzyme preparation from intestinal mucosa of rat, rabbit, guinea-pig and monkey was distinctly different in electrophoretic mobility and in elution profile on ion-exchange chromatography, possibly due to their difference in charge. The difference may not be due to glycosylation, since the enzyme was not stained for glycoprotein. Polyclonal antibody against purified monkey enzyme inhibited the activity of intestinal CuZn superoxide dismutase from rat, rabbit and guinea-pig. Thus it appears that intestinal CuZn superoxide dismutases from different sources, despite being similar in immunological and other properties, differ in certain amino acids and hence in charge. PMID- 1905270 TI - Effect of anti-Ig on rabbit B cell function and Ig expression. AB - We have examined the effect which xenogeneic anti-Ig has on rabbit B cell function and Ig expression in an effort to understand the phenomenon of antibody mediated suppression. Treatment of rabbit lymphocyte cultures with xenogeneic anti-rabbit Ig causes 2.5-3.8 fold decrease in the level of Ig secreting cells with little or no long-term effect on surface Ig. This suppression in B cell secretory function is not the result of suppression of Ig gene expression since xenogeneic anti-rabbit Ig treatment causes a 1.7-2.7 fold increase in Ig L and H chain mRNA levels. Collectively, these data are consistent with the hypothesis that antibody mediated suppression of B cell function occurs at a post transcriptional level involving either the secretory pathway of Ig expression and/or blockage in B cell differentiation. PMID- 1905272 TI - Effects of indomethacin on prostaglandin E2 and thromboxane B2 contents of tracheal lavage fluids in premature infants. AB - A prospective longitudinal study was conducted in 14 premature infants intubated and receiving ventilatory support from birth, in order to evaluate the levels of prostaglandins E2 (PGE2) and thromboxane B2 (TxB2) in the tracheal lavage fluids (TLF) after treatment with indomethacin. Eight were treated with indomethacin, a cyclooxygenase inhibitor, for patient ductus arteriosus and the others served as controls. Infants who received indomethacin during the first postnatal week had significantly lower levels of eicosanoids in TLF during the first week. Our results suggest that levels of eicosanoids in TLF of premature infants are related to an inflammatory reaction and may serve as an index of the infant's overall clinical condition. PMID- 1905273 TI - Is idiopathic atrial fibrillation caused by occult thyrotoxicosis? A study of one hundred consecutive patients with atrial fibrillation. AB - In this study we evaluated the possible relationship between idiopathic atrial fibrillation and occult thyrotoxicosis, diagnosed by lack of response of thyroid stimulating hormone to administration of thyrotropin releasing hormone. Three groups were compared: 25 patients with idiopathic atrial fibrillation; 52 with cardiovascular atrial fibrillation; and 27 with sinus rhythm. Patients were excluded with any clinical evidence of thyrotoxicosis or with elevated serum FT4 level, as well as those with diseases or on medications known to be associated with a diminished response to administration of the releasing hormone. A flat test (lack of response) was found in only 4% of the patients. There was no significant difference among the 3 groups. Based on these data we believe that there is no relationship between idiopathic atrial fibrillation or any other type of atrial fibrillation and occult thyrotoxicosis. PMID- 1905271 TI - Comparison of arachidonate metabolism by alveolar macrophages from bighorn and domestic sheep. AB - We have defined the metabolites of arachidonic acid (AA) secreted by alveolar macrophages (AMs) of bighorn sheep and domestic sheep in response to three agents: calcium ionophore A23187, phorbol myristate acetate (PMA), and opsonized zymosan. Cells were labeled with [3H]AA prior to stimulation and 11 tritiated metabolites, including prostaglandins (PGs), thromboxanes (TXs), leukotrienes (LTs), and hydroxyeicosatetraenoic acids (HETEs), were detected and quantitated by high-performance liquid chromotography and radiometry. Zymosan stimulation resulted in the release of significantly elevated quantities (P less than 0.05), of LTB4, [5(S), 12(R)-dihydroxy-6,14-cis-8,10-trans-eicosatetraenoic acid], 5 HETE, [5(S)-hydroxyeicosatetraenoic acid], and the nonenzymatic isomers of LTB4, [LTB I, 5(S),12(R)-6-trans-LTB4] and LTB II, [5(S), 12(S)-6-trans-LTB4], from domestic sheep AM when compared to bighorn sheep AM. Phorbol myristate acetate (PMA) stimulation released significantly elevated quantities (P less than 0.04), of TXB2, (thromboxane B2), HHT, [12(S)-12-hydroxy-5,8,10-heptadecaenoic acid], LTB I, LTB II, and 15-HETE, [15(S)-hydroxyeicosatetraenoic acid] from domestic sheep AMs when compared to bighorn sheep AMs. However, after A23187 challenge, only 15-HETE was significantly elevated (P less than 0.04) in domestic sheep AMs when compared to bighorn sheep AMs. These clear differences in AA metabolism of AMs obtained from bighorn and domestic sheep in response to three different agonists suggest not only different control mechanisms for lung metabolism of AA in the two species, but also suggest that differences in the metabolites released may lead to quite different regulation of lung defense mechanisms in the two sheep species. PMID- 1905274 TI - Ventilatory threshold during exercise in patients with mild to moderate chronic heart failure: determination, relation with lactate threshold and reproducibility. AB - Detection of the ventilatory threshold during exercise has been proposed in order to assess exercise tolerance in patients with chronic heart failure. The relation between the different methods of detecting the ventilatory threshold and the lactate threshold, however, and their reproducibility, have not really been assessed. Forty-three patients with chronic heart failure underwent an exercise test with respiratory gas analysis. A lactate threshold could be determined in 36 patients and a ventilatory threshold in 27 to 38 patients, depending on the method of determination of the ventilatory threshold. The greatest number of determinations (38) and the best correlation coefficient with the lactate threshold (r = 0.87 and 0.88, respectively) were obtained with the method of the ventilatory equivalent for oxygen and by averaging the different methods of determination. Reproducibility of the ventilatory threshold was only moderately good (r = 0.83) and less satisfactory than that of the peak oxygen uptake (r = 0.97). We conclude that unless the way of detecting the ventilatory threshold is improved in patients with chronic heart failure, the peak oxygen uptake will remain more reproducible. PMID- 1905275 TI - [Ischemic stroke (focal cerebral ischemia)]. PMID- 1905276 TI - Glycosaminoglycan and collagen metabolism in arylsulfatase B-deficient retinal pigment epithelium in vitro. AB - Regional differences in retinal pigment epithelial (RPE) cell glycosaminoglycan (GAG) and collagen metabolism were studied using cells obtained from normal cats and those with deficient activity of arylsulfatase B (ASB), a lysosomal enzyme involved in GAG catabolism. Control and ASB-deficient RPE cultures initiated from superior equatorial (superior) and inferior equatorial (inferior) regions of the eye were radiolabeled for 72 hr with 35SO4, and GAGs from the media and cell layers were analyzed separately. In ASB-deficient RPE, there was an accumulation of dermatan/chondroitin sulfate in the cell layer of cultures initiated from the superior region of the eye but not in those initiated from the inferior region. This agrees with previous in situ and in vitro morphologic observations that accumulation of inclusions in ASB-deficient RPE was greater in the superior region of the eye than in the inferior region. By contrast, media from ASB deficient cultures initiated from the inferior region of the eye contained much higher levels of radiolabeled dermatan/chondroitin sulfate than ASB-deficient cultures from the superior region or normal cultures. Increased GAG content in the media may result from increased secretion of proteoglycans, increased turnover of cell surface or extracellular matrix components, or extrusion of lysosomal contents. These results indicate that one or more of these mechanisms vary regionally throughout the eye in the RPE of ASB-deficient animals. Collagen production was determined in normal and ASB-deficient RPE cultures. In normal RPE, no differences in collagen synthesis were noted between the inferior and superior regions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1905277 TI - Characterization of pseudomonal adherence to unwounded cornea. AB - This study examined binding of Pseudomonas aeruginosa to unwounded postnatal day (P) 5 immature mouse cornea. To determine whether the receptor molecule was protein or lipid in nature, the eyes were incubated in vitro with trypsin or lipase before bacteria were applied. Trypsin significantly increased bacterial binding, whereas lipase had no effect. To determine if enhanced binding after trypsin indicated exposure of a lipid or a protein receptor, the eyes were treated sequentially with trypsin, then lipase. Subsequent binding did not differ significantly from trypsin alone, indicating that the exposed receptor was not a lipid. Incubation of the P 5 eye with neuraminidase to remove sialylated residues also significantly enhanced binding at all times, and premixing of the inoculum with the enzyme before adherence testing increased binding at 15 and 30 min. The effects of a monosialoganglioside (GM1) and gangliotetraosylceramide (asialo GM1) were also examined. Incubation of eyes with GM1 or asialo GM1 produced no significant inhibition of bacterial binding, but premixing of the bacterial inoculum with GM1 or asialo GM1 before corneal application transiently decreased adherence. Fibronectin (FN) treatment of the P 5 eye, premixing FN with the bacterial inoculum before its ocular application, or similar treatment with N acetylneuraminic acid (NANA) transiently inhibited binding. These data demonstrate that pseudomonal binding to the unwounded eye is not lipase sensitive and is enhanced by trypsin treatment which exposes a lipase insensitive receptor and by neuraminidase which removes sialylated residues. It is not inhibited by pretreatment of the eye with either GM1 or asialo GM1 and is transiently inhibited by pretreatment of the eye or the inoculum with NANA or FN. PMID- 1905278 TI - The permeability of the rabbit corneal epithelium and endothelium to mannitol. PMID- 1905279 TI - Comparison of efficiency and profitability of investor-owned multihospital systems with not-for-profit hospitals. AB - It is often assumed that investor-owned hospitals are more market driven than are not-for-profit hospitals, and that they will maximize output and minimize inputs, to the exclusion of other management strategies. To resolve the conflicting research evidence, this study analyzed efficiency and profitability measures for approximately 50 investor-owned and 60 not-for-profit hospitals in Florida for the period from 1982 through 1988. The results indicate that the investor-owned hospitals used significantly fewer FTE staff per bed, had significantly fewer manhours per adjusted patient day, and paid significantly less in wages and had significantly higher operating margins (profit) than did the not-for-profit institutions. PMID- 1905280 TI - [Hyperprolactinemia and hypophyseal hypothyroidism as cofactors in hirsutism and androgen-induced alopecia in women]. AB - A more comprehensive hormonal diagnosis than has previously been performed shows that androgen-dependent diseases of hair growth are due to more varied hormonal disturbances than elevated androgen serum levels alone. In 46 female patients with androgenic hair loss and 27 patients with hirsutism, the levels of the androgens testosterone, free testosterone, androstenedione, dehydroepiandrosterone sulphate and 17-hydroxyprogesterone and of sex hormone binding globulin, cortisol, oestradiol and the hypophyseal hormones follicle stimulating hormone and luteinizing hormone were determined and compared with the hormone levels of 27 female patients without endocrine disorders. Of the androgens, only androstenedione showed a slightly significant elevation in hirsutism. Cortisol was elevated significantly in androgenic hair loss, and with a low degree of significance in hirsutism. In view of the complex hormonal interactions of thyroxin, prolactin and androgens and thyroid hormones the thyrotropin-releasing hormone (TRH)-stimulation test was performed in 38 female patients with androgenic hair loss and 27 with hirsutism, and the results were compared with those recorded in 45 female control persons. The test is based on feedback mechanisms between hypothalamic TRH and hypophyseal TSH and prolactin and peripheral thyroid hormones. Baseline concentrations of TSH prior to stimulation were significantly elevated in hirsutism, while in androgenic hair loss both baseline and stimulated TSH levels were significantly elevated; thus, hypothyroidism is a significant finding in both clinical pictures. In the case of prolactin, both baseline and stimulated levels were highly significantly elevated in hirsutism, while in androgenic hair loss the stimulated levels were significantly elevated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1905281 TI - The survival of Listeria monocytogenes in cottage cheese. AB - Because of the difficulty of ensuring that cottage cheese is produced in conditions that prevent contamination with Listeria monocytogenes, the ability of this bacterium to survive in cottage cheese from three sources was investigated (a) during shelf-life at chill temperature and (b) in conditions of temperature abuse. Three batches of creamed cottage cheese, from three sources, received within 24 h of production, were inoculated with L. monocytogenes strain F6861 and stored at 4, 8 or 12 degrees C for 14 d. The three batches differed in their initial pH, titratable acidity and content of lactic acid and of lactic acid bacteria. No increase in numbers of L. monocytogenes occurred in the cottage cheeses during storage in these conditions. The numbers of listeria decreased; the rate of decrease differed in products from the three sources and was least in the product with the highest pH and lowest content of lactic acid. Acid formation by lactic acid bacteria during storage of the products probably contributed to the inhibition of listeria. PMID- 1905282 TI - Differentiation of dairy strains of the Bacillus cereus group by phage typing, minimum growth temperature, and fatty acid analysis. AB - A total of 130 Bacillus strains were isolated from dairy products, the dairy environment and from packaging boards and board-producing machines. Ninety-eight of these were members of the B. cereus group (B. cereus, B. mycoides and B. thuringiensis) as determined by whole cell fatty acid composition. Fatty acid composition did not differentiate between the three species. Of the 98 strains, which were indistinguishable by biochemical tests, 87 could be assigned into 21 different phage types (11 strains remained untypable) when tested with 12 B. cereus, B. mycoides and B. thuringiensis phages. The distribution of phage types between strains from different sources showed that the source of contamination of the dairy products was of milk origin and not from the packaging materials. Most strains isolated from the dairy products were able to grow below 10 degrees C, whereas strains from the dairy environment and from board mills had higher minimum growth temperatures. PMID- 1905283 TI - Growth of Bacillus cereus in fermenting tempeh made from various beans and its inhibition by Lactobacillus plantarum. AB - Counts of Bacillus cereus reached ca 10(8) cfu/g within 40 h in fermenting unacidified horsebean tempeh and resulted in complete spoilage of the product. In fermenting unacidified pea, chickpea and soybean tempeh, B. cereus counts reached 10(6)-10(7) cfu/g, although the products were not spoiled. Inoculation of these unacidified beans with Lactobacillus plantarum decreased the final count of B. cereus by 2 log units, but had no effect on its growth in unacidified horsebean tempeh and its subsequent spoilage. Acidification of the beans during soaking resulted in a lower rate of B. cereus growth during fermentation. Inoculation of acidified beans with Lact. plantarum resulted in a markedly lower growth rate of B. cereus. In an associative broth culture study, B. cereus was completely inhibited by Lact. plantarum at pH values of about 5.5. Lactobacillus plantarum may be used to control the growth of B. cereus during tempeh production. PMID- 1905284 TI - Induction and cultivation of a stable L-form of Bacillus subtilis. AB - The induction of L-forms of Bacillus subtilis from protoplasts is described. The method involved the frequent subculture of the unstable L-form on a growth medium supplemented with lysozyme and horse serum. A stable culture, which did not revert when lysozyme and horse serum were omitted from the medium, was obtained after 13 subcultures. This culture could be grown on solid and in liquid medium by routine microbiological methods. Long-term storage of these cells was achieved by freeze drying and maintenance in glycerol at -70 degrees C. The cultural adaptability of the L-form is described and discussed with respect to methods of cultivation and growth. PMID- 1905286 TI - The sensitivity index, a calculation to improve the choice of antibacterial therapy. PMID- 1905285 TI - Susceptibility of Pseudomonas aeruginosa and Escherichia coli biofilms towards ciprofloxacin: effect of specific growth rate. AB - Methods of cell culture which enable the control of specific growth rate and expression of iron-regulated membrane proteins within Gram-negative biofilms were employed for various clinical isolates of Pseudomonas aeruginosa taken from the sputum of cystic fibrosis patients and of a laboratory strain of Escherichia coli. Susceptibility towards ciprofloxacin was assessed as a function of growth rate for intact biofilms, cells resuspended from the biofilms and also for newly formed daughter cells shed from the biofilm during its growth and development. Patterns of susceptibility with growth rate were compared to those of suspended cultures grown in a chemostat. In all instances the susceptibility of chemostat cultures was directly related to growth rate. Whilst little difference was observed in the susceptibility pattern for P. aeruginosa strains with different observed levels of mucoidness, such populations were generally more susceptible towards ciprofloxacin than those of E. coli. At fast rates of growth P. aeruginosa cells resuspended from biofilms were significantly more resistant than chemostat grown cells. Intact P. aeruginosa biofilms were significantly more resistant than cells resuspended from them. This is in contrast to E. coli, where cells resuspended from biofilm and intact biofilms were, at the slower rates of growth, equivalent and significantly more susceptible than chemostat-grown cells. At high growth rates all methods of E. coli culture produced cells of equivalent susceptibility. For all strains, daughter cells dislodged from the biofilms demonstrated a high level of susceptibility towards ciprofloxacin which was unaffected by growth rate. This sensitivity corresponded to that of the fastest grown cells in the chemostat. PMID- 1905287 TI - A sensitivity index from diffusion susceptibility tests. PMID- 1905288 TI - Effect of withdrawal of respiratory CO2 oscillations on respiratory control at rest. AB - We examined the effect of sudden withdrawal of respiratory oscillations of arterial PCO2 (CO2 oscillations) at resting metabolic rate on the control of respiration in 11 anesthetized paralyzed vagotomized dogs in normoxic normocapnia. A double-lumen endotracheal tube was inserted so that the left and right lungs were ventilated independently. By alternately ventilating each lung, we could completely abolish CO2 oscillations without affecting the mean blood gas levels (withdrawal of CO2 oscillations). The CO2 oscillation was calculated from arterial pH oscillation measured by a rapidly responding intra-arterial pH electrode. Respiratory center output was monitored by use of a moving time average of the phrenic neurogram. A 3-min period of withdrawal of CO2 oscillations was bracketed by two control periods (simultaneous ventilation of lungs for 3 min) to avoid the confounding effect of the baseline drift in the respiratory center output. The amplitude of the CO2 oscillations in the control was 2.33 +/- 0.89 (SD) Torr. When the difference in the mean level of arterial PCO2 between the control and withdrawal of CO2 oscillations was minimized (-0.09 +/- 0.54 Torr; P greater than 0.25), we found negligible change in the minute phrenic activity during withdrawal of CO2 oscillations (-0.02 +/- 6.11% of the control, P greater than 0.98, n = 49; 99% confidence interval -2.36 to 2.32%). Thus we conclude that the maintenance of normal respiration at rest is not critically dependent on a phasic afferent input to the respiratory center arising from respiratory CO2 oscillations. PMID- 1905289 TI - Filtration-assisted exchange transfusion using alpha alpha Hb, an erythrocyte substitute. AB - A method for improving the efficiency of exchange transfusion to evaluate hemoglobin- (Hb) based erythrocyte substitutes is described. The method uses a continuous-flow hollow-fiber plasma separation filter to remove the erythrocytes while returning 75% of the plasma. The removed volume was replaced with a 14-g/dl solution of human Hb cross-linked between the alpha-chains with bis(3,5 dibromosalicyl)fumarate (alpha alpha Hb). Filtration of 2.76 blood vol in anesthetized swine resulted in a 95% reduction of hematocrit and produced a plasma Hb concentration of 7.63 g/dl. Hyperoncotic Hb solutions cause volume expansion, which reduces the efficiency of exchange but provides hemodynamic stability in the face of decreasing blood viscosity and subsequent intravascular volume loss with Hb redistribution. Filtration-assisted exchange transfusion is rapid, conserves valuable modified Hb, and ensures continuous adequate oxygen delivery. PMID- 1905290 TI - Analysis of abnormalities of capillary CO2 exchange in vivo. AB - Capillary CO2 exchange in vivo is affected by several interdependent reactions and transport processes. A mathematical model that includes all the significant chemical and transport events that are presumed to occur during capillary gas exchange has been used to investigate the effect of inhibition of 1) erythrocyte HCO(3-)-Cl- exchange, 2) lung carbonic anhydrase (CA) activity with access to plasma, and 3) erythrocyte CA activity on overall pulmonary CO2 excretion (VCO2) during rest and moderate exercise. Any decrement in VCO2 due to inhibition of HCO(3-)-Cl- exchange and/or CA activity, should result in compensatory alterations in cardiac output and/or an increase in the mixed venous blood-to alveolar PCO2 gradient [(delta PCO2)V-A] to restore steady-state VCO2. Our computations show that complete inhibition of erythrocyte anion exchange would require a compensatory increment in cardiac output of approximately 30-40% or an increase in (delta PCO2)V-A from 6 to 8.3 Torr at rest and from 12 to 15.6 Torr during moderate exercise, if lung CA activity is intact. In the absence of availability of lung CA activity to plasma, the necessary (delta PCO2)V-A is 10.5 Torr at rest and 19.5 Torr during moderate exercise. Complete inhibition of lung and erythrocyte CA activity is predicted to require (delta PCO2)V-A of 39.1 Torr at rest and 74.2 Torr during moderate exercise. These results suggest that HCO(3 )-Cl- exchange might not be vital to maintenance of CO2 transfer and perhaps has a more important role in minimizing the changes in plasma pH associated with microvascular gas exchange in vivo. PMID- 1905291 TI - Umbilical cord occlusion stimulates breathing independent of blood gases and pH. AB - The role of umbilical cord occlusion in the initiation of breathing at birth was investigated by use of 16 unanesthetized fetal sheep near full term. Artificial ventilation with high-frequency oscillation was used to control fetal arterial blood gas tensions. At baseline, PCO2 was maintained at control fetal values and PO2 was elevated to between 25 and 50 Torr. In the first study on six intact and four vagotomized fetuses, arterial PCO2 and PO2 were maintained constant during two 30-min periods of umbilical cord occlusion. Nevertheless, the mean fetal breathing rate increased significantly when the umbilical cord was occluded. In the second study on six intact fetuses, hypercapnia (68 Torr) was imposed by adding CO2 to the ventilation gas. When the umbilical cord was occluded, there was a significantly greater stimulation of breathing (rate, incidence, and amplitude) in response to hypercapnia than in response to hypercapnia alone. During cord occlusion, plasma prostaglandin E2 concentration decreased significantly. Results indicate that cord occlusion stimulates breathing possibly by causing the removal of a placentally produced respiratory inhibitor such as prostaglandin E2 from the circulation. PMID- 1905293 TI - Long-term follow-up and benefit-cost analysis of the Jobs Program: a preventive intervention for the unemployed. AB - Results are reported from a 2 1/2 year follow-up of respondents who participated in a randomized field experiment that included the Jobs Program, a preventive intervention for unemployed persons. The intervention was intended to prevent poor mental health and loss of motivation to seek reemployment and to promote high-quality reemployment. The results of the long-term follow-up were consistent with those found 1 and 4 months after intervention (Caplan, Vinokur, Price, & van Ryn, 1989). The results demonstrate the continued beneficial effects of the intervention on monthly earnings, level of employment, and episodes of employer and job changes. These findings are supported by a benefit-cost analysis, which demonstrates large net benefits of the intervention to the participants and to the federal and state government programs that supported the project. PMID- 1905292 TI - PEEP inhibits hypoxic pulmonary vasoconstriction in dogs. AB - The effects of an increase in alveolar pressure on hypoxic pulmonary vasoconstriction (HPV) have been reported variably. We therefore studied the effects of positive end-expiratory pressure (PEEP) on pulmonary hemodynamics in 13 pentobarbital-anesthetized dogs ventilated alternately in hyperoxia [inspired O2 fraction (FIO2) 0.4] and in hypoxia (FIO2 0.1). In this intact animal model, HPV was defined as the gradient between hypoxic and hyperoxic transmural (tm) mean pulmonary arterial pressure [Ppa(tm)] at any level of cardiac index (Q). Ppa(tm)/Q plots were constructed with mean transmural left atrial pressure [Pla(tm)] kept constant at approximately 6 mmHg (n = 5 dogs), and Ppa(tm)/PEEP plots were constructed with Q kept constant approximately 2.8 l.min-1.m-2 and Pla(tm) kept constant approximately 8 mmHg (n = 8 dogs). Q was manipulated using a femoral arteriovenous bypass and a balloon catheter in the inferior vena cava. Pla(tm) was held constant by a balloon catheter placed by left thoracotomy in the left atrium. Increasing PEEP, from 0 to 12 Torr by 2-Torr increments, at constant Q and Pla(tm), increased Ppa(tm) from 14 +/- 1 (SE) to 19 +/- 1 mmHg in hyperoxia but did not affect Ppa(tm) (from 22 +/- 2 to 23 +/- 1 mmHg) in hypoxia. Both hypoxia and PEEP, at constant Pla(tm), increased Ppa(tm) over the whole range of Q studied, from 1 to 5 l/min, but more at the highest than at the lowest Q and without change in extrapolated pressure intercepts. Adding PEEP to hypoxia did not affect Ppa(tm) at all levels of Q.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1905294 TI - Thyroid stimulating hormone response to thyrotropin in prepubertal depression. AB - In an effort to evaluate whether differences exist in the hypothalamic-pituitary thyroid axis of depressed children, a thyrotropin releasing hormone (TRH) stimulation test was administered to 55 prepubertal subjects who were divided into three groups matched for age and sex: a depressed group (endogenous N = 15, nonendogenous N = 15), a psychiatric nondepressed control group (N = 16), and a normal control group (N = 9). Each subject was tested at two dosages of TRH, 2 micrograms/kg and 7 micrograms/kg. Increasing age and female sex were positively correlated with a greater thyroid stimulating hormone (TSH) response. TSH response to TRH was examined with subjects reclassified by severe suicidal ideation, severe aggression, and parental history of alcoholism. Results of this study are contrasted with the adult psychiatric literature. PMID- 1905295 TI - Extracorporeal circulation in the fetal lamb. Effects of hypothermia and perfusion rate. AB - The poor prognosis of certain cardiac abnormalities detected prenatally by echocardiography has led some investigators to consider intrauterine cardiac surgery. Investigation into the efficacy of open cardiac procedures in-utero will require techniques for safe and effective fetal extracorporeal circulation and myocardial protection. We performed cardiopulmonary bypass in 8 fetal lambs to assess the feasibility of fetal cardiopulmonary bypass. Four fetuses underwent studies at 37 degrees C (Group I) and 4 at 25 degrees C (Group II). The aorta was clamped and cold crystalloid cardioplegia administered. Perfusion was carried out for 10 minutes each at high (95 +/- 18 cc/kg/min), moderate (67 +/- 10 cc/kg/min), and low (49 +/- 8 cc/kg/min) flow rates while hemodynamic and blood gas measurements were made. Total time on bypass averaged 57 min in Group I and 75 min in Group II. Four fetuses were successfully weaned from bypass following the study period. Fetal pO2 and oxygen saturation was very low at all flow rates in Group II and at low flow rates in Group I, indicating poor function of the placenta as an oxygenator at 25 degrees C and at low flow rates during normothermia. Lambs undergoing bypass at 37 degrees C had a progressive rise in pCO2 levels as flow decreased, while pCO2 was relatively normal at all flow rates at 25 degrees C. These studies serve as a starting point for the development of techniques to allow intrauterine correction of experimentally produced fetal cardiac lesions. PMID- 1905296 TI - Non-neuronal 210 x 10(3) Mr microtubule-associated protein (MAP4) contains a domain homologous to the microtubule-binding domains of neuronal MAP2 and tau. AB - A polyclonal antiserum raised against a HeLa cell microtubule-associated protein of Mr 210,000 (210 kD MAP or MAP4), an abundant non-neuronal MAP, was used to isolate cDNA clones encoding MAP4 from a human fetal brain lambda gt11 cDNA expression library. The largest of these clones, pMAP4.245, contains an insert of 4.1 kb and encodes a 245 kD beta-galactosidase fusion protein. Evidence that pMAP4.245 encodes MAP4 sequences includes immunoabsorption of MAP4 antibodies with the pMAP4.245 fusion protein, as well as identity of protein sequences obtained from HeLa 210 kD MAP4 with amino acid sequences encoded by pMAP4.245. The MAP4.245 cDNA hybridizes to several large (approximately 6-9 kb) transcripts on Northern blots of HeLa cell RNA. DNA sequencing of overlapping MAP4 cDNA clones revealed a long open reading frame containing a C-terminal region with three imperfect 18-amino acid repeats; this region is homologous to a motif present in the microtubule (MT)-binding domain of two prominent neuronal MAPs, MAP2 and tau. The pMAP4.245 sequence also encoded a series of unrelated repeats, located in the MAP's projection domain, N-terminal to the MT-binding domain. MAP4.245 fusion proteins bound to MTs in vitro, while fusion proteins that contained only the projection domain repeats failed to bind specifically to MTs. Thus, the major human non-neuronal MAP resembles two neuronal MAPs in its MT binding domain, while most of the molecule has sequences, and presumably functions, distinct from those of the neuronal MAPs. PMID- 1905297 TI - Cooperative enhancement of hyaluronic acid synthesis by combined use of IGF-I and EGF, and inhibition by tyrosine kinase inhibitor genistein, in cultured mesothelial cells from rabbit pericardial cavity. AB - We examined the combined effects of IGF-I and EGF on hyaluronic acid synthesis using cultured pericardial mesothelial cells from rabbit pericardial cavity. Combined exposure of pericardial cells to IGF-I and EGF cooperatively increased hyaluronic acid synthesis and the level of hyaluronic acid synthase activity over that seen with or without IGF-I or EGF alone, but did not significantly stimulate the sulfated glycosaminoglycan synthesis. Increase in the level of hyaluronic acid synthesis and hyaluronic acid synthase activity induced by these growth factors was blocked after pretreatment with a tyrosine-specific protein kinase inhibitor, genistein. Genistein had no direct inhibitory effect on hyaluronic acid synthase activity. These results suggest that cooperative enhancement of hyaluronic acid synthesis induced by combined use of IGF-I and EGF could be mediated by a receptor tyrosine kinase-involved transmembrane signaling process that is responsive to IGF-I and EGF. PMID- 1905298 TI - Glycosylation mutations of serine/threonine-linked oligosaccharides in low density lipoprotein receptor: indispensable roles of O-glycosylation. PMID- 1905299 TI - Colour genes, oncogenes and melanocyte differentiation. PMID- 1905301 TI - Eosinophilia, activated eosinophils and human schistosomiasis. PMID- 1905300 TI - abnormal chromatin (abc), a maternal-effect locus in Drosophila melanogaster. AB - Mutations in the maternal-effect gene abnormal chromatin (abc) in Drosophila melanogaster result in a variety of defects involving nuclear replication/division. Three recessive alleles of this gene, which maps near 51F on chromosome 2, all result in female sterility. They cause slower embryonic development that is usually abnormal from the earliest nuclear divisions and arrested by the sixth one. Nuclei tend to be large and erratically distributed, some intensely staining. Mitotic asynchrony is common. Few embryos reach the gastrula stage and none hatch. With the weakest allele, fsPL, bridges between nuclei are common; abnormal chromatin clumps that resemble yolk nuclei occur before the other nuclei reach the surface; and spindle anomalies and DNA wads with numerous centrosomes are seen. Females with the stronger alleles, fsA5 and fs27, lay fewer eggs and a smaller proportion of embryos reach blastoderm; developmental arrest occurs earlier, usually with several large nuclei distributed along the length of the embryo. Chorion defects occur in all three mutants. Mitotic asynchrony, nuclear bridging, endoreduplication and nuclear behavior aberrant from the first division suggest that the abc gene product operates in DNA replication/nuclear division. Larval (homozygous F1) neuroblast chromosome structure and mitotic indices are normal, indicating that any mitotic function is strictly maternal, i.e. abc is not a general mitotic gene. Thus abc is one of a few known genes with a maternal effect that appears to function in the embryonic cell cycle. PMID- 1905302 TI - High-performance liquid chromatographic analysis of 2',3'-dideoxyinosine in biological samples. AB - A high-performance liquid chromatographic analysis for the anti-AIDS drug 2',3' dideoxyinosine (ddI) in rat plasma and urine, with a limit of detection of 0.2 microgram/ml and requiring a sample size of 100 microliters is described. Diluted plasma or urine samples were extracted using a C18 solid-phase extraction column. Retention of ddI on more polar solid-phase extraction columns was insufficient for sample clean-up. This method is useful for pharmacokinetic studies of ddI in small rodents. PMID- 1905303 TI - T-cell abnormality and defective interleukin-2 production in patients with carcinoma of the urinary bladder with schistosomiasis. AB - Patients with schistosomiasis of the urinary bladder (SB) and schistosomiasis with carcinoma of the urinary bladder (SCB) had significantly increased percentage of IL-2R-, HLA-DR-, and transferrin receptor (T9)-bearing T cells in circulation. The percentage of these activated T cells decreased by in vitro culture with PHA but increased by Schistosoma haematobium soluble egg antigen. These patients with SB and SCB had a PHA-specific defect in IL-2 production. A functional defect with induction of IL-2R-positive suppressor monocytes appears to correlate with the defective PHA-induced IL-2 production by CD4+ T cells and monocytes. Disordered regulation of PHA-induced IL-2 production by the CD4+ T cells and monocytes may be the key feature in the highly depressed cell-mediated immune response in schistosomiasis. However, immune activation and significantly elevated IL-2 production in response to disease-specific S. haematobium soluble egg antigen may be related with the pathogenesis of SB and SCB. Thus, S. haematobium-specific CD4+ T cells are present in schistosomiasis, and their function is determined by adequate release of IL-2-and/or IL-2R-bearing CD11+ suppressor monocytes. PMID- 1905304 TI - Human tuberculosis sera show prominent antibody responses to particulate fractions of Mycobacterium tuberculosis. AB - Sera from smear-positive pulmonary tuberculosis patients and normal control subjects in Madras were analyzed by Western blotting for their reactivity with soluble and particulate (membrane-rich and cell wall-rich) antigen fractions extracted by sonication from Mycobacterium tuberculosis H37Rv. Discrimination between patient and control sera was best with particulate antigen fractions: 60% of patient sera reacted with a 38-kD antigen band and 90% reacted with a 55-kD band. Reactions of control sera with the 38- and 55-kD bands were infrequent and faint. The results suggest that a serodiagnostic test might be based on quantitation of responses to these two antigens. PMID- 1905307 TI - Development of ovarian cysts during gonadotrophin-releasing hormone agonists (GnRHa) administration. AB - The incidence of ovarian cyst formation during stimulation with additional pituitary suppression was retrospectively studied in 359 patients included in our in-vitro fertilization (IVF) programme. Women were classified according to the type of pituitary desensitization with subcutaneous buserelin used in group A (long protocol; n = 285) and group B (short protocol; n = 74). The rate of appearance of single follicular ovarian cysts for group A was 9.82% and for group B 22.97% (P less than 0.005). Ovarian cystic formations were usually asymptomatic and nonfunctional. The presence of these cysts did not seem to interfere with the ovarian response to stimulation treatment. Oocyte retrieval and pregnancy rate were similar between patients who developed ovarian cysts during gonadotrophin releasing hormone analogue (GnRHa) therapy and those without cyst formation. These results suggest that ovarian cysts developing during GnRHa treatment are probably the consequence of the initial gonadotrophin rise and that the presence of ovarian cysts in these conditions should not be considered a necessary cause of cancellation for IVF patients. PMID- 1905308 TI - Effects of in-vitro exposure to HCG on subsequent HCG-responsiveness of human granulosa cells obtained following treatment with GnRH analogue and gonadotrophins: an in-vitro model for luteal phase support. AB - The pregnancy rate in patients undergoing assisted conception treatment following pituitary desensitization with GnRH analogue and ovarian stimulation with gonadotrophins has been reported to be higher when ovarian function is supported in the luteal phase by exogenous human chorionic gonadotrophin (HCG). In the present study, we have examined the effects of culturing monolayers of granulosa cells, collected from such patients at oocyte retrieval, for various time intervals in the presence or absence of HCG on their subsequent ability to secrete progesterone (P4) either spontaneously or in response to further challenge with HCG. When cultured in the absence of HCG, granulosa cells demonstrated a rapid decline in both the spontaneous P4 secretion rate and the ability to secrete P4 in response to HCG. Maintenance in the presence of HCG inhibited the rapid decline in ability to secrete P4 spontaneously and also significantly enhanced the ability to respond to subsequent HCG stimulation. These results suggest that HCG support in the luteal phase in GnRH analogue treated patients may have a cellular basis for its action both in maintenance of P4 secretion and also in rendering the corpus luteum more sensitive to rescue by conceptus-derived HCG. PMID- 1905305 TI - Evidence that the interaction between circulating IgA and fibronectin is a normal process enhanced in primary IgA nephropathy. AB - A solid-phase ELISA was set up to measure the direct binding capacity (BC) of different, commercially available, purified human IgA preparations to plates coated with human fibronectin (FN). It was found that secretory, polymeric, and, to a much lesser extent, monomeric IgA exhibited elevated FN-BC as compared to their BC to plates coated with bovine serum albumin. This binding was specific since not observed with human IgG or IgM antibodies. In addition, we noted that this interaction was dose dependent, Ca2+ dependent, saturable, and not covalent, was inhibited by soluble FN, but not by a prior incubation of FN-coated plates with anti-human fibronectin antibodies, and appeared to involve on the dimeric FN other structures than its heparin-binding, collagen-binding, or C1q-binding domains. Similar experiments conducted with normal plasma indicated that plasma IgA, but not plasma IgG or IgM, was also capable of significant binding to FN coated plates. In contrast, serum IgA did not significantly bind to those plates under otherwise identical experimental conditions. Thus, the coagulation process induces a strong decrease in the FN-BC of circulating IgA, which implies the necessity of using plasma rather than serum to study such interactions. The apparent molecular weight of plasma IgA interacting with FN-coated plates ranged between 450 and 900 kd, and its major binding characteristics were quite similar to those observed with purified polymeric IgA. The FN-BC of plasma IgA was then measured by the same ELISA in 30 patients with primary IgA nephropathy (IgAN) and in 23 healthy controls. The mean FN-BC of plasma IgA was significantly higher in patients than in normal controls. This enhancement was due mainly to the augmentation in the concentration of circulating "macromolecular" IgA and was significantly correlated with the plasma levels of IgA-FN complexes. However, the pathogenetic role of these findings was probably not determinant since similar observations were made in alcoholic liver cirrhosis without urinary abnormalities and since the FN-BC of plasma IgA or the plasma levels of IgA-FN complexes were not correlated with the various biological parameters of evolutivity of primary IgAN. In conclusion, these studies suggest that the ability of polymeric IgA to directly bind to FN is involved in the formation of circulating IgA-FN complexes and that this normal binding process, although enhanced in IgAN, is probably not responsible for kidney injury, at least in the patients studied. PMID- 1905309 TI - Differential effects of gonadotrophin-releasing hormone agonists administered as desensitizing or flare protocols on hormonal function in the luteal phase of hyperstimulated cycles. AB - The incorporation of gonadotrophin-releasing hormone agonist (GnRHa) in in-vitro fertilization (IVF) stimulation protocols has led to doubt about the quality of the subsequent luteal phase. The effects of two GnRHa stimulation protocols on luteal phase concentrations of oestradiol (E2), progesterone (P), luteinizing hormone (LH) and follicle stimulating hormone (FSH) were compared with the standard clomiphene stimulation regimen. Subjects receiving clomiphene with human menopausal gonadotrophin (HMG, n = 377) showed essentially similar luteal phase P concentrations to those receiving leuprolide acetate/HMG as a desensitization protocol. Subjects receiving concomitant leuprolide and HMG from day 2 to utilize the flare effect of the GnRHa exhibited significantly lower P levels in the luteal phase compared to clomiphene/HMG and leuprolide desensitization protocols despite the addition of HCG support. This occurred despite equivalent E2 concentrations at the time of ovulation and identical numbers of oocytes recovered. LH concentrations in non-conception cycles were suppressed for at least 14 days in the luteal phase in both GnRHa protocols compared to clomiphene stimulation. Differences were less obvious in cycles where conception occurred suggesting that implantation may proceed more favourably when the luteal endocrinology was optimal. It is concluded that flare methods of GnRHa hyperstimulation are associated with significantly different luteal phases compared with clomiphene or desensitization protocols. It is proposed that the use of the flare type of stimulation may significantly influence the response of the granulosa cells to LH or HCG via gonadotrophin receptors or through altered post-receptor function. PMID- 1905306 TI - Role of elevated monocyte transforming growth factor beta (TGF beta) production in posttrauma immunosuppression. AB - We previously reported that increased production of prostaglandin E2 by monocytes is a pivotal mechanism in posttrauma immunopathology. Here we characterize monocyte levels of transforming growth factor beta and examine the effects of elevated transforming growth factor beta on prostaglandin E2 release by patients' monocytes. Trauma patients' and normals' monocyte supernates (+/- stimulation with muramyl dipeptide) were acid treated and assayed for transforming growth factor beta using the mink lung-cell bioassay. Alternatively, human transforming growth factor beta was added to patients' and normals' monocytes and prostaglandin E2 production assayed. Significantly elevated transforming growth factor beta levels (median = 181.7 pmol/10(6) monocytes) were detected in immunosuppressed patients' monocytes but not immunocompetent trauma patients' (median = 32.0 pM) or normals' (median = 20.4 pM) monocytes. Adding transforming growth factor beta to monocytes resulted in a significant elevation of prostaglandin E2 levels. Elevated monocyte transforming growth factor beta levels in trauma patients could be both suppressing T-lymphocyte functions and maintaining elevated monocyte prostaglandin E2 synthesis. PMID- 1905310 TI - Blunted prolactin response to exogenous luteinizing hormone releasing hormone in superovulated women. AB - To investigate the prolactin (PRL) response to luteinizing hormone releasing hormone (LHRH) in superovulated cycles, eight normally ovulating women were studied in two cycles, i.e. a spontaneous (control) and a cycle treated with 'pure' follicle stimulating hormone (FSH) (225 IU/day). LHRH was given to the women i.v. (a single injection of 100 micrograms) in the late follicular phase of both cycles. The oestradiol levels (mean +/- SEM) at the time of the LHRH challenge were 635 +/- 31 and 1707 +/- 225 pmol/l respectively (P less than 0.001). The size of the leading follicle was similar in both cycles. Basal PRL levels (mean +/- SEM) on the day of the LHRH experiment were significantly higher in the FSH (250 +/- 31 microIU/ml) than in the spontaneous cycles (133 +/- 15 microIU/ml. P less than 0.05). In the latter cycles, LHRH induced a significant increase in serum PRL and LH levels, while the FSH cycles, the prolactin (PRL) response to LHRH was blunted and LH response markedly attenuated. We conclude that superovulation induction stimulates basal but suppresses LHRH-induced PRL release. It is suggested that basal PRL secretion is LHRH-independent and the suppressing effect is mediated via previously described paracrine interactions between the gonadotrophs and lactotrophs and/or through ovarian inhibitory substances. PMID- 1905311 TI - Pure FSH for ovulation induction in patients with polycystic ovary syndrome and resistant to clomiphene citrate therapy. AB - Twenty-nine infertile women with polycystic ovary disease which was resistant to therapy with clomiphene citrate underwent a combined treatment for follicle recruitment consisting of pure FSH during the first days of the cycle and HMG during the last days of the follicular phase. Sixty cycles were stimulated of which 83% were ovulatory. Eighteen pregnancies were achieved (36% of cycles, 62% of patients). The multiple pregnancy rate was 39%. Twelve cycles (20%) showed the ovarian hyperstimulation syndrome (OHS) although seven of these resulted in full term deliveries. There were no miscarriages among the patients studied. PMID- 1905312 TI - The value of menotrophin treatment for unexplained infertility prior to an in vitro fertilization attempt. AB - This work was undertaken in order to evaluate retrospectively the relative efficacy of ovulation induction by menotrophins and that of in-vitro fertilization and embryo transfer (IVF-ET) in the treatment of unexplained infertility. These two treatments were compared between two groups of patients: 87 couples undergoing 446 cycles of ovulation induction by menotrophins (group A) and 72 couples undergoing 108 cycles of IVF-ET (group B). A total of 30 and 20 pregnancies were achieved in groups A and B for a rate of 34 and 28% per patient, respectively. A similar cumulative pregnancy rate (CPR) was achieved for three cycles of ovulation induction (23%) and one cycle of IVF-ET (22%). The cumulative live birth rate (CLBR) in group A was 22% after three cycles and exceeded that of one IVF-ET cycle (17%). It is concluded that menotrophin treatment in unexplained infertility is highly beneficial and should precede an IVF attempt. PMID- 1905313 TI - Folliculogenesis and ovulation in infertile women with mild endometriosis. AB - Twenty-one infertile women with laparoscopically documented minimal-mild endometriosis (AFS score 2-10) were studied during 27 cycles (six women had two cycles each) to investigate follicular development and ovulation. Of the 27 cycles studies, 24 (89%) appeared to be endocrinologically normal and ovulatory. Luteinized unruptured follicle (LUF) occurred in only one cycle (4%). One further patient exhibited abnormal endocrinology with evidence of premature ovulation over two (8%) consecutive cycles. This study indicates that the majority of women with minimal-mild endometriosis have endocrinologically normal menstrual cycles and that luteinized unruptured follicles occur infrequently. PMID- 1905314 TI - In-vitro fertilization in infertile women with the polycystic ovarian syndrome. AB - Forty-four infertile patients with the polycystic ovarian syndrome (PCOS) resistant to other treatment modalities were treated in 58 cycles of IVF after accomplishment of pituitary gonadotroph suppression with a GnRH-agonist. Four cycles were cancelled before oocyte retrieval while embryo transfer was deferred for 10 cycles due to imminent ovarian hyperstimulation syndrome (OHSS). Follicle aspiration yielded 18.8 +/- 9 oocytes per cycle. The cleavage rate was 68%. There was no cleavage in five cycles. The pregnancy rate was 33.3% per embryo transfer. In 32 cycles 9.0 +/- 5 suitable supernumerary embryos were cryopreserved. Transfer of cryopreserved embryos gave three additional pregnancies. The accumulated pregnancy rate per patient was 36%. In clomiphene citrate resistant patients, transfer of cryopreserved embryos was accomplished after secretory transformation of the endometrium by oestradiol/progesterone substitution. Although seven pregnancies ended in a miscarriage, the 'take-home' baby rate was 20%. OHSS ensued in 28 (46.7%) cycles. In PCOS, in-vitro fertilization following pituitary gonadotroph suppression seems a treatment alternative with pregnancy rates comparable to normo-ovulatory women with tubal factor infertility. However, the incidence of OHSS is high and constitutes the major problem of cycle control. PMID- 1905315 TI - The effect of prostaglandins and aspirin--an inhibitor of prostaglandin synthesis -on adhesion formation in rats. AB - The effect of intraperitoneal application of prostaglandins E2 and F2 alpha and of aspirin, a non-steroidal anti-inflammatory drug, on the formation of intraperitoneal adhesions was investigated in rats, in view of the main role of the body's reaction in adhesion formation. Intraperitoneal adhesions were induced by inflicting uniform trauma to the uterine serosa. It was demonstrated that prostaglandin E2 may increase adhesion formation and that intraperitoneal aspirin is able to inhibit its formation. PMID- 1905316 TI - Combined impact of the number of pre-ovulatory oocytes and cryopreservation on IVF outcome. AB - Three hundred and twenty-seven consecutive in-vitro fertilization (IVF) cycles in which luteal-phase leuprolide had been given were ranked according to the number of pre-ovulatory oocytes obtained (1-5, 6-10, greater than 10). Excess pre embryos were cryopreserved at the pronuclear stage and later transferred into monitored natural cycles on the day after ovulation. The results indicate that the retrieval of large numbers of pre-ovulatory oocytes (greater than 10) has a small negative impact on oocyte quality as judged by fertilization rates (4% lower). However, implantation was not impaired compared to lower levels of retrieval in either the original IVF or subsequent cryo-thaw cycles. Overall, despite the small reduction in fertilization rate, the retrieval of many pre ovulatory oocytes has produced a 'take-home baby rate' per stimulation cycle of 28.3% when 6-10 pre-ovulatory oocytes were retrieved and 41.5% when greater than 10 were retrieved: even higher rates are anticipated when the remaining cryopreserved pre-embryos are ultimately thawed. PMID- 1905317 TI - The influence of inadvertent intranasal buserelin administration in early pregnancy. AB - Buserelin was inadvertently administered during 13 early pregnancies in 12 women with long-standing infertility, who had started the GnRH-agonist for gonadotrophin desensitization prior to ovarian stimulation for IVF. Six women delivered a healthy child and one pregnancy continues uneventfully. Three patients aborted before the sixth week and three women with tubal disease had an ectopic pregnancy. Corpus luteum function was normal in 11 of the 13 pregnancies. Although no evidence of embryotoxic effects of buserelin was observed, barrier contraceptive methods should be advised during the first days of its administration. PMID- 1905318 TI - Ultrasonic evaluation of endometrial growth in women with normal cycles during spontaneous and stimulated cycles. PMID- 1905319 TI - Unusual case of Aeromonas hydrophila endocarditis. AB - We describe a case of Aeromonas hydrophila endocarditis in a 66-year-old man with myelodysplastic syndrome and non-A, non-B hepatitis, The infection resolved with antibiotic therapy, but the patient succumbed to complications of his underlying illness. This is the second case of Aeromonas endocarditis reported in the world literature. PMID- 1905320 TI - Comparison of Gen-Probe DNA probe test and culture for the detection of Neisseria gonorrhoeae in endocervical specimens. AB - A 2-h nonisotopic DNA probe assay for the direct detection of Neisseria gonorrhoeae in urogenital specimens has recently been modified (PACE 2; Gen Probe, San Diego, Calif.). The new assay format was developed to increase the sensitivity of the assay and simplify procedural steps. In this study, the new DNA probe test was compared with a culture reference method for the detection of N. gonorrhoeae in endocervical specimens. The results of the DNA probe test were expressed as a ratio of relative light units (RLU) of the specimen/RLU of the cutoff recommended by the manufacturer. All patient samples with sample RLU/cutoff RLU ratios less than 0.7 were interpreted as negative, and ratios greater than 2.0 were interpreted as positive for gonorrhea. Samples with sample RLU/cutoff RLU ratios between 0.7 and 2.0 were repeated until two or more consistent negative or positive ratios were obtained. A total of 469 specimens were tested with an overall disease prevalence of 6.1%. Of the 469 patients tested, 5 specimens (1.0%) fell in this borderline region and were retested. If the manufacturer's recommended cutoff value had been used, the original DNA probe results would have resulted in two false-positives. Our data were analyzed for both symptomatic (prevalence, 11.7%) and asymptomatic (prevalence, 2%) women. The study indicated that with our modification of the manufacturer's endpoint interpretation, the DNA probe test was essentially equivalent to the culture method in terms of sensitivity, specificity, and positive and negative predictive values in both symptomatic and asymptomatic patient populations. The new DNA probe test can serve as a suitable screening and diagnostic test for the diagnosis of gonorrheal genital infections in women. Additionally, it offers the advantages of rapid turnaround time and ease of use and allows simultaneous testing for Chlamydia trachomatis on the same specimen. PMID- 1905321 TI - Dot blot hybridization assay for chicken anemia agent using a cloned DNA probe. AB - A dot blot hybridization assay capable of detecting chicken anemia agent (CAA) specific DNA in tissues from infected birds has been developed. The assay uses a 32P-labeled DNA probe prepared from cloned CAA-specific fragments representing the entire virus genome and has a sensitivity limit of between and 1 and 10 pg. DNAs from CAA isolates originating in the Federal Republic of Germany, Japan, the United States, the United Kingdom, and Australia were detected. Investigation of specimens from experimentally infected chicks indicated that virus-specific DNA was detected in the tissues of birds from 5 through 42 days after infection and that greater amounts were usually detected in the thymus than in the spleen, liver, feces, or blood. Tissues from specific-pathogen-free and broiler chicks which had become infected at an older age through contact with experimentally infected anemic chicks also contained CAA-specific DNA detectable by the assay. Thymuses from 1- to 2-week-old chicks from eight commercial broiler flocks which had been showing clinical signs characteristic of anemia-dermatitis syndrome were found positive by the hybridization technique, but thymuses from chicks obtained from broiler flocks which did not show such signs were found negative. Of the 35 positive samples (from 46 samples tested), 19 (54%) contained virus-specific DNA in sufficiently great amounts to permit 4-h autoradiography exposures and sample throughput times of 2 days. When compared with virus isolation, the CAA dot blot hybridization assay is time- and labor-saving. PMID- 1905322 TI - Effects of FP2 and a mercury resistance plasmid from Pseudomonas aeruginosa PA103 on exoenzyme production. AB - Plasmids encoding mercury resistance carried by Pseudomonas aeruginosa PAO1161 and PA103 were found to be involved in regulating the secretion of protease, phospholipase C, and alkaline phosphatase. Previously, mutations in Pseudomonas strains that caused pleiotropic effects on the production of extracellular enzymes were mapped to the bacterial chromosome. We show that pleiotropic changes in extracellular enzyme production can also be regulated by plasmids. In this study, the effects on secretion of exoenzymes by two mercury resistance plasmids, FP2 from PAO1161 and pRLW103 from PA103, were assayed in P. aeruginosa PAO1 and PAO18. The introduction of either plasmid into PAO1 resulted in a significant decrease in exoprotease production. Additionally, pRLW103 significantly increased the production of alkaline phosphatase by both strains. Phospholipase C was produced only in strain PAO18 containing the pRLW103 plasmid. FP2 had no effect on alkaline phosphatase or phospholipase C production in either strain and was found to decrease exoprotease secretion only in strain PAO1. The results indicate the P. aeruginosa mercury resistance plasmids vary in their ability to modify exoenzyme expression, and this ability is influenced by the host strain. PMID- 1905324 TI - Global budgeting and the control of hospital costs. AB - This paper attempts to answer the question: Would global budgeting control hospital costs in the United States? It reviews the development of health insurance and the growth of specialization in the United States, as well as the experience of Canada in attempting to control costs in a fee-for-service national medical care program. It concludes that the main causes of cost escalation in the U.S. are fee-for-service and overspecialization, and urges adoption of the NAPHP proposal for payment of physicians in a national program, i.e. global budgeting for the entire package of ambulatory and institutional services. It also presents a nine-point program for immediate State action to lower costs. PMID- 1905323 TI - Cytopathogenic effects in enterocytelike Caco-2 cells differentiate virulent from avirulent Listeria strains. AB - We have developed a simple test that differentiates between virulent and avirulent Listeria species as defined by the mouse 50% lethal doses (LD50S). The assay is based on trypan blue-revealed cytopathogenic effects that are produced during the infection of the human enterocytelike cell line Caco-2. These effects were elicited only by Listeria strains that had an intraperitoneal mouse LD50 less than 10(8) and were not produced by nonhemolytic, avirulent strains of Listeria monocytogenes generated spontaneously or by Tn916 mutagenesis or by avirulent Listeria species. A negative test was also obtained with hemolysin producing, avirulent L. monocyotogenes NCTC5105 and Listeria ivanovii KC1786. The test was negative with avirulent L. monocytogenes strains which are strong inducers of opacity in egg yolk agar. However, a strain which has a low LD50, such as 10(4), may show less severe cytopathogenic effects than a strain having a higher LD50, such as 10(6). The test has been effectively used to screen for virulent listerial isolates, spontaneous mutants, and transposon-induced mutants. PMID- 1905325 TI - Characterization of rabbit ileal receptors for Clostridium difficile toxin A. Evidence for a receptor-coupled G protein. AB - The purpose of this study was to characterize the surface receptor for toxin A, the enterotoxin from Clostridium difficile, on rabbit intestinal brush borders (BB) and on rat basophilic leukemia (RBL) cells. Purified toxin A was radiolabeled using a modified Bolton-Hunter method to sp act 2 microCi/micrograms, with retention of full biologic activity. 3H-Toxin A bound specifically to a single class of receptors on rabbit BB and on RBL cells with dissociation constants of 5.4 x 10(-8) and 3.5 x 10(-8) M, respectively. RBL cells were highly sensitive to toxin A (cell rounding) and had 180,000 specific binding sites per cell, whereas IMR-90 fibroblasts were far less sensitive to toxin A and lacked detectable specific binding sites. Exposure of BB to trypsin or chymotrypsin significantly reduced 3H-toxin A specific binding. Preincubation of BB with Bandeirea simplicifolia (BS-1) lectin also reduced specific binding, and CHAPS-solubilized receptors could be immobilized with WGA-agarose. The addition of 100 nM toxin A accelerated the association of 35S-GTP gamma S with rabbit ileal BB, and preincubation of BB with the GTP analogues GTP gamma S or Gpp(NH)p, significantly reduced 3H-toxin A specific binding. Our data indicate that the membrane receptor for toxin A is a galactose and N-acetyl-glucosamine containing glycoprotein which appears to be coupled to a G protein. PMID- 1905326 TI - An independent effect of osmolality on urea transport in rat terminal inner medullary collecting ducts. AB - We have shown that urea transport across the terminal inner medullary collecting duct (terminal IMCD) is mediated by a vasopressin-stimulated, facilitated diffusion process exhibiting properties consistent with a transporter. To investigate whether hypertonic NaCl, as exists in vivo in the inner medulla, affects urea permeability, we studied isolated perfused rat terminal IMCD segments. Perfusate and bath osmolality were varied symmetrically by adding or removing NaCl or mannitol. Urea permeability rose progressively when osmolality was increased with NaCl or mannitol from 290 to 690 mOsm/kg H2O in the absence of vasopressin; there was no further increase at 890 mOsm/kg H2O. In the presence of 10(-8) M arginine vasopressin, urea permeability increased when NaCl was added to raise osmolality from 290 to 490 mOsm/kg H2O but there was no further increase at 690 mOsm/kg H2O. When 1 mM 8-bromo cyclic AMP was added to the bath, raising NaCl still increased urea permeability. These results suggest that urea transport across the rat terminal IMCD is regulated both by vasopressin and by osmolality at values present in the renal inner medulla. Osmolality seems to activate urea transport across the rat terminal IMCD by mechanisms distinct from those of vasopressin or cyclic AMP. PMID- 1905327 TI - Intestinal immune responses in humans. Oral cholera vaccination induces strong intestinal antibody responses and interferon-gamma production and evokes local immunological memory. AB - We have examined secretory antibody and cell-mediated immune responses to oral cholera vaccine in the human gastrointestinal mucosa. Freshly isolated peripheral blood lymphocytes and intestinal lymphocytes obtained by enzymatic dispersion of duodenal biopsies were assayed for numbers of total and vaccine specific immunoglobulin-secreting cells by enzyme-linked immunospot assay (ELISPOT) techniques; the frequency of cells secreting interferon-gamma (IFN-gamma) was also examined by a new modification of the ELISPOT technique. After booster immunizations with oral cholera vaccine, large numbers of cholera toxin-specific antibody-secreting cells (ASC) appeared in the small intestine. The responses were dominated by IgA ASC. A single immunization, performed 5 mo after the initial vaccinations, gave rise to an ASC response similar to that seen after the first booster immunization, with respect to both magnitude and isotype distribution. Each of the immunizations also evoked an ASC response in blood which was of lower magnitude than that seen in the small intestine, and comprised similar proportions of IgA and IgG ASC. A booster immunization also resulted in increased frequencies of IFN-gamma-secreting cells, but this increase was confined to the duodenal mucosa. This study establishes the feasibility of studying, at the single-cell level, intestinal immune reactivity in humans. Furthermore, it indicates that the small intestinal mucosa is an enriched source of IFN-gamma. It also demonstrates marked differences between intestinal and peripheral blood immune responses after enteric immunization, and confirms the notion that the mucosal immune system in humans displays immunological memory. PMID- 1905328 TI - Reduction in susceptibility to natural killer cell-mediated lysis of human FO-1 melanoma cells after induction of HLA class I antigen expression by transfection with B2m gene. AB - Induction of HLA class I antigens on cultured melanoma cells FO-1 after transfection with a human or a mouse B2m gene was associated with a statistically significant reduction in their susceptibility to natural killer (NK) cell mediated lysis. These results indicate that the structural differences between human and mouse beta 2-mu do not abolish the ability of the HLA class I molecular complex to modulate NK cell-mediated lysis of melanoma cells FO-1. The role of HLA class I antigens in the phenomenon is corroborated by the ability of anti-HLA class I MAb to enhance, although to a different extent, the susceptibility of transfected FO-1 cells to NK cell-mediated lysis. Gamma interferon (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) significantly reduced the susceptibility to NK cell-mediated lysis of transfected FO-1 cells. Surprisingly, TNF-alpha reduced the extent of lysis more than IFN-gamma, although the latter cytokine enhanced HLA class I antigen expression more than the former one. This finding, in conjunction with a reduction in the susceptibility to NK cell mediated lysis of untransfected FO-1 cells incubated with IFN-gamma or TNF-alpha, suggests that the two cytokines reduce NK cell-mediated lysis of transfected cells by modulating not only the expression of HLA class I antigens, but also that of other structures. Induction of HLA class I antigens and their modulation with IFN-gamma did not affect the susceptibility to lymphokine-activated killer (LAK) cell-mediated lysis of transfected FO-1 cells. Characterization of the molecular mechanism(s) underlying abnormalities in HLA class I antigen expression by melanoma cells and of the role of these molecules in the interactions of melanoma cells with various types of effector cells may suggest novel immunotherapeutic approaches to melanoma. PMID- 1905329 TI - Organ specific cytokine therapy. Local activation of mononuclear phagocytes by delivery of an aerosol of recombinant interferon-gamma to the human lung. AB - In the context of the central role of the alveolar macrophage in host defense of the respiratory epithelial surface, and the ability of IFN-gamma to activate mononuclear phagocytes, we have evaluated strategies to use rIFN-gamma to activate human alveolar macrophages in vivo. To accomplish this, rIFN-gamma was administered to nonsmoking normals, the amounts of IFN-gamma quantified in serum and respiratory epithelial lining fluid (ELF) and the status of IFN-gamma related activation of blood monocytes and alveolar macrophages was evaluated by quantifying the expression of mRNA transcripts of IP-10, a gene induced specifically by IFN-gamma. Systemic administration (subcutaneous) of maximally tolerated amounts of rIFN-gamma (250 micrograms) was followed by detectable levels of IFN-gamma in serum but not ELF, the expression of IP-10 transcripts in blood monocytes but not alveolar macrophages, and multiple systemic adverse effects. To circumvent the inability of systemic administration to reach respiratory ELF and activate alveolar macrophages, rIFN-gamma (250-1,000 micrograms) was inhaled as an aerosol once daily for 3 d. Strikingly, while IFN gamma was not detected in serum it was detectable in respiratory ELF in a dose dependent fashion. Further, alveolar macrophages, but not blood monocytes, expressed IP-10 mRNA transcripts and, importantly, inhalation of aerosolized rIFN gamma was not associated with local or systemic adverse effects. Thus, it is feasible to use rIFN-gamma to activate alveolar macrophages by targeting the cytokine directly to the lung. These data suggest a potential strategy for targeted cytokine therapy, without systemic side effects, to augment respiratory tract defenses in individuals at risk for or with lung infection. PMID- 1905331 TI - Autocrine stimulation of interleukin-1 alpha and transforming growth factor alpha production in human keratinocytes and its antagonism by glucocorticoids. AB - Interleukin-1 (IL-1) and transforming growth factor alpha (TGF alpha) mRNA expression was analyzed in cultured normal human keratinocytes. Keratinocytes constititively express IL-1 mRNA when cultured in keratinocyte growth medium but not in Dulbecco's minimal essential medium containing fetal bovine serum, in which the cells differentiate. The predominant form of IL-1 expressed by keratinocytes is IL-1 alpha. Addition of IL-1 alpha to keratinocytes increased IL 1 alpha and TGF alpha mRNA expression in a dose-dependent manner. TGF alpha induced a similar increase in IL-1 alpha and TGF alpha mRNA in keratinocytes. Hydrocortisone decreased the expression of both IL-1 alpha and TGF alpha mRNA in keratinocytes. These findings document an autocrine mechanism by which IL-1 alpha and TGF alpha can stimulate the proliferation of keratinocytes in the skin. It is proposed that this autocrine loop may be hyperactive in psoriasis. Antagonism of the effects of this autocrine loop may be one of the mechanisms by which glucocorticoids exert clinically useful effects in psoriasis and other diseases of the skin. PMID- 1905330 TI - Regulation of phospholipase D and primary granule secretion by P2-purinergic- and chemotactic peptide-receptor agonists is induced during granulocytic differentiation of HL-60 cells. AB - We have compared the abilities of extracellular ATP (acting via P2-purinergic receptors) and formylated peptides (FMLP) to stimulate both phospholipase D (PLD) based signal transduction and primary granule (azurophilic) secretion in HL-60 cells induced to differentiate along the granulocytic pathway. In undifferentiated HL-60 cells, neither ATP nor FMLP elicited significant PLD activation or increased secretion despite the previously documented ability of ATP to stimulate large increases in polyphosphoinositide hydrolysis and Ca2+ mobilization. Conversely, within 1 d after induction of granulocytic differentiation by dibutyryl cAMP, both ATP and FMLP induced large increases in azurophilic secretion and corresponding increases in PLD activity. ATP-activated PLD activity was near-maximal within 1 d after dibutyryl cAMP treatment, while the FMLP-induced activity increased continuously over 4 d, with a maximal level twice that stimulated by ATP. Additional experiments characterized the activation of PLD by receptor-independent pathways at different stages of differentiation; these included studies of phorbol ester action in intact cells and GTP gamma S action in electropermeabilized cells. An apparent role for guanine nucleotide binding regulatory proteins in PLD regulation was also indicated by the significant reduction in FMLP- and ATP-stimulated PLD activity observed in cells pretreated with pertussis toxin. At all stages of differentiation, there was good correlation between the relative efficacies of ATP versus FMLP in stimulating both secretion and PLD activity. These data indicate: (a) that the receptor regulated phospholipase D signaling pathway is induced during differentiation of myeloid progenitor cells; and (b) that differential activation of this signaling system by various Ca(2+)-mobilizing receptor agonists may underlie the differential regulation of secretion and other phagocyte functions by such agents. PMID- 1905332 TI - Interferon decreases the growth inhibition of Mycobacterium avium-intracellulare complex by fresh human monocytes but not by culture-derived macrophages. AB - Using a rapid radiolabel assay, monocytes derived from the peripheral blood of normal donors were found to kill 40%-92% of inoculated Mycobacterium avium intracellulare complex (MAC), an opportunistic pathogen commonly found in AIDS patients. However, bactericidal activity was significantly lower in 4-day culture derived macrophages compared with matched monocyte cultures. The addition of interferon-gamma (IFN-gamma) to monocytes was found to inhibit the bactericidal activity of fresh monocytes. The number of bacteria recovered from fresh monocytes exposed to IFN-gamma was significantly higher than that in control cultures with MAC alone, suggesting that intracellular MAC growth could be stimulated by IFN-gamma. This enhancement of MAC survival and growth by IFN-gamma was not observed when culture-derived macrophages were used. Similar results were obtained with IFN-alpha/A2. These results indicate, therefore, that the innate efficiency of mycobacterial killing by monocytes can be down-regulated by IFN, but macrophages are not significantly affected. PMID- 1905333 TI - [Effects of continuous lighting on secretion of melatonin and pituitary hormones in women]. AB - Effects of light exposure on the serum concentrations of melatonin, prolactin, LH and FSH were studied in 53 women during their follicular phases. Twenty seven women were exposed to light (500-800 lux at eye level) from 17:30h to 22:00h, and 17 women received the same light intensity from 17:30h to 2:00h, while 9 women stayed in a dark room from 21:00h to 2:00h as control subjects. The light exposure suppressed a nocturnal increase in the serum concentrations of melatonin both at 22:00h and 2:00h. The light exposure and awake condition suppressed the serum prolactin concentrations and increased the serum FSH concentrations at 2:00h, while the influence on the serum LH concentrations was not clear because of LH pulsatility. These results show that the circadian rhythm of melatonin, prolactin and FSH is affected by light exposure and wakefulness, and the effects of light exposure would become more evident if light exposure was continued over a longer period. PMID- 1905334 TI - [Roentgenological manifestation of ossification of the posterior longitudinal ligament in the cervical spine causing severe spinal canal stenosis--a group comparison with and without marked spinal cord dysfunction]. AB - Relationship between the degree of clinical symptoms and the lateral roentgenograms of the cervical OPLL causing severe spinal canal stenosis was studied among patients whose roentgenological minimum antero-posterior diameters of the available spinal canals were under 9mm. Lateral roentgenograms of 28 clinically mild patients were compared with those of 20 clinically severe patients. The type of ossification, the extent of OPLL, the narrowest level of the available spinal canal, and the minimum a-p diameter were not statistically significant parameters. The degree of canal stenosis at the 1cm cranial and 1cm caudal levels from the narrowest level, and the axial extent of canal stenosis around the narrowest level were less significantly in the group with mild symptoms than in the group with severe symptoms. PMID- 1905335 TI - Differential modulation of surface antigens on human macrophages by IFN-gamma and GM-CSF: effect on susceptibility to LAK lysis. AB - We have previously reported that cultured human monocytes are lysed by autologous lymphokine-activated killer (LAK) cells in vitro and that treatment of monocytes with interferon-gamma (IFN-gamma) decreased their sensitivity to lysis. Conversely, incubation of monocytes with granulocyte-macrophage colony stimulating factor (GM-CSF) significantly enhanced their susceptibility to LAK mediated cytotoxicity. To determine if certain antigens were differentially modulated on macrophages by IFN-gamma and GM-CSF, cytokine-treated and untreated monocytes were analyzed for the expression of a variety of cell surface markers by flow cytometry. Cytotoxicity assays were performed to assess the ability of antibodies to each of these markers to block LAK lysis of macrophage target cells. While several of the surface structures were differentially modulated by cytokine treatment, it was found that only monoclonal antibodies to the adhesion proteins CD11a and CD18 were capable of blocking lysis of either cytokine-treated or untreated target macrophages. PMID- 1905337 TI - A subpopulation of mouse cytotoxic T lymphocytes recognizes allogeneic H-2 class I antigens in the context of other H-2 class I molecules. AB - Recently, independent lines of evidence strongly suggested that peptides derived from one foreign major histocompatibility complex (MHC) molecule bound to another MHC molecule can give rise to multiple composite MHC complexes that are able to stimulate allo-(xeno)-reactive T cells. In this study, we describe that in vivo immunization of mice with cells mismatched with the recipient for a single class I antigen results in the induction of CD8+ cytotoxic T lymphocytes (CTL) specific for allogeneic class I locus products (Dd, Kd, Dq) in the context of other class I molecules (Ks, Kd, Kk) present on stimulator cells. Evidently, the target antigen for these class I-restricted alloreactive CTL is not the native class I molecule but peptides derived from endogenous processing of allogeneic class I products presented by class I molecules. Using a combination of limiting dilution and split-well analyses, we estimated for Kk-restricted Dq-specific alloreactive CTL a precursor frequency (CTLpf) that was approximately 10 times lower than the CTLpf for "classical" nonrestricted Dq-specific alloreactive CTL. These data suggest that H-2 class I peptides presented by intact H-2 class I molecules are allostimulatory, supporting the concept that the capacity for presentation of MHC peptides by MHC molecules constitutes a part of the allogeneic immune response. PMID- 1905336 TI - Nonconventional (TL-encoded) major histocompatibility complex molecules present processed viral antigen to cytotoxic T lymphocytes. AB - A large number of class I-like genes are located distal to the K and D regions of the murine major histocompatibility complex (MHC) within the Q and TL region. The function of the molecules encoded within this region is obscure since unlike conventional MHC gene products, these molecules have not been reported to present processed environmental antigens to T cells. In the present report, we demonstrate that a peptide corresponding to processed influenza virus hemagglutinin can be recognized by CD8+ T cell receptor alpha/beta-positive cytotoxic T lymphocytes (CTL) in association with a MHC class I-like product encoded within the TL region. Thus, nonconventional class I MHC molecules can bind and present processed environmental antigens, and TCR-alpha/beta CTL directed to such peptide MHC complexes are represented in the mature T cell pool. Our data imply that Q/TL region products may be charged by peptides generated through an antigen processing and presentation pathway distinct from the pathway used by conventional MHC molecules and not normally available to environmental antigens. PMID- 1905338 TI - CD4-CD8- T cell receptor alpha beta T cells: generation of an in vitro major histocompatibility complex class I specific cytotoxic T lymphocyte response and allogeneic tumor rejection. AB - The generation of an in vitro major histocompatibility complex class I specific response of CD4-CD8- T cell receptor (TCR) alpha beta cytotoxic T lymphocytes (CTL) and their allogeneic tumor rejection were investigated. Inocula of BALBRL male 1 were rejected in C57BL/6 (B6) mice treated with minimum essential medium (MEM) (control), anti-L3T4 (CD4) monoclonal antibody (mAb) or anti-Lyt-2.2 (CD8) mAb and CTL against the tumor were generated in vitro. No rejection and no induction of CTL were observed in B6 mice treated with anti-L3T4 (CD4) plus anti Lyt-2.2 (CD8) mAb. CTL with the classical Thy-1+ CD3+CD4-CD8+ TCR alpha beta phenotype were generated in mixed lymphocyte tumor cell culture (MLTC) spleen cells from B6 mice treated with MEM (control) or anti-L3T4 (CD4) mAb, whereas CTL with an unusual Thy-1+CD3+CD4-CD8- TCR alpha beta phenotype were generated in MLTC spleen cells from anti-Lyt-2.2 (CD8) mAb-treated B6 mice. Both types of CTL were reactive with both H-2Kd and Dd (Ld) class I antigen. These findings suggest that when CD4+ cells were blocked by anti-L3T4 (CD4) mAb, CD8+ CTL mediated rejection, and when CD8+ cells were blocked by anti-Lyt-2.2 (CD8) mAb, CD4+ cells were capable of mediating rejection, although less efficiently than CD8+ cells, by inducing CD4-CD8- TCR alpha beta CTL. The finding that adoptive transfer of CD4 and CD8-depleted MLTC spleen cells, obtained from anti-Lyt-2.2 (CD8) mAb treated B6 mice that had rejected BALBRL male 1, resulted in rejection of BALBRL male 1 inoculated into B6 nu/nu mice confirmed the above notion. CTL clones with the CD4-CD8- TCR alpha beta phenotype specific for Ld were established. PMID- 1905339 TI - Infection of lymphocytes by a virus that aborts cytotoxic T lymphocyte activity and establishes persistent infection. AB - For viruses to establish persistent infections in their hosts, they must possess some mechanism for evading clearance by the immune system. When inoculated into adult immunocompetent mice, wild-type lymphocytic choriomeningitis virus (LCMV ARM) induces a CD8(+)-mediated cytotoxic T lymphocyte (CTL) response that clears the infection within 7-14 d (CTL+ [P-]). By contrast, variant viruses isolated from lymphoid tissues of persistently infected mice fail to induce a CTL response and are thus able to establish a persistent infection in adult mice (CTL- [P+]). This report compares the interaction of CTL+ (P-) and CTL- (P+) viruses with cells of the immune system. Both types of virus initially bind to 2-4% of CD4+ and CD8+ T lymphocytes and replicate within cells of both subsets. The replication of CTL- (P+) and CTL+ (P-) viruses in lymphocytes in vivo is similar for the first 5 d after initiating infection. Thereafter, in mice infected with CTL- (P+) variants, lymphocytes retain viral genetic information, and infectious virus can be recovered throughout the animals' lives. In contrast, when adult mice are infected with wild-type CTL+ (P-) LCMV ARM, virus is not recovered from lymphocytes for greater than 7 d after infection. A CD8(+)-mediated anti-LCMV CTL response is induced in such mice. Clearance of infected lymphocytes is produced by these LCMV-specific CTLs, as shown by their ability to lyse lymphocytes expressing LCMV determinants in vitro and the fact that depletion of CD8+ lymphocytes before infection with CTL+ (P-) viruses results in levels of infected lymphocytes similar to those found in undepleted CTL- (P+)-infected mice. Hence, CTL-mediated lysis of T lymphocytes carrying infectious virus is a critical factor determining whether virus persists or the infection is terminated. PMID- 1905340 TI - The expression of several T cell-specific and novel genes is repressed by trans acting factors in immature T lymphoma clones. AB - Cell surface proteins encoded by members of the immunoglobulin supergene family are sequentially expressed during T cell ontogeny. The molecular mechanisms responsible for the regulation of these surface molecules are not well understood. To investigate this issue, we used a series of well characterized T lymphoma cell clones with phenotypes characteristic of distinct stages of early thymocyte maturation. Somatic cell hybrids formed from these cell lines were employed to detect the presence of negative regulatory molecules. The expression of CD4 and CD8 was strongly repressed in hybrids formed between a CD4+ CD8+ lymphoma clone and "immature" CD4- CD8- lymphoma clones. Individual subunits of the T cell receptor (TCR)/CD3 complex displayed independent regulation in unique patterns in hybrid cells. Hybrids formed by fusing CD3+ and CD3- cells completely repressed CD3-delta mRNA expression while CD3-gamma, -epsilon, and -zeta transcripts were moderately inhibited or codominantly regulated. Similar to CD3 delta, interleukin 2R-alpha(IL-2R-alpha), and TCR-beta mRNA accumulation was trans-negatively regulated. Transcription rate measurements demonstrated that the inhibition of CD4, CD8, CD3-gamma, CD3-epsilon, TCR-beta, and IL-2R-alpha mRNA accumulation in hybrid cells was exerted, at least in part, at the transcriptional level. To test whether repressional regulation is a general feature of T cells, we examined the regulation of six novel genes which were selected solely on the basis of their differential expression between two of the cell lines used in this study. Five of the six novel gene transcripts were repressed in the somatic cell hybrids. Thus, inhibitor factors appear to play a general role in controlling T cell gene expression. The model system presented here may be useful for the identification and characterization of repressor molecules responsible for the regulation of genes expressed during T cell ontogeny. PMID- 1905342 TI - Fluid resuscitation. PMID- 1905341 TI - A gamma/delta cell receptor heterodimer induces the expression of CD4 and CD8 in thymocytes. AB - CD4 and CD8 have been useful surface markers for alpha/beta T cell maturation. In an alpha/beta T cell receptor (TCR) transgenic SCID mice system, it has been shown that alpha/beta TCR alone is sufficient to induce CD4 and CD8 surface expression on thymic T cells. Although the late embryonic thymic gamma/delta T cells are predominately single and double positive, it has not been clear if gamma/delta TCR has a similar capacity. In this study, we show that when transgenes encoding the earliest embryonic gamma/delta TCR are coexpressed with the SCID defect, the gamma/delta transgenes promote the appearance of both the CD4-8- and CD4+8+ T cells in the thymus. Furthermore, the expression of CD4 and CD8 does not require continuous surface gamma/delta TCR expression. These results indicate that gamma/delta TCR alone can promote the CD4/8 surface expression, and may suggest a role for gamma/delta T cells in initiating normal thymic ontogeny. PMID- 1905343 TI - Thrombolytic therapy during active menstruation: a case report. PMID- 1905344 TI - The role of the inositol phosphate cascade in visual excitation of invertebrate microvillar photoreceptors. AB - The identity of the transmitter(s) involved in visual transduction in invertebrate microvillar photoreceptors remains unresolved. In this study, the role of inositol 1,4,5-trisphosphate (IP3) was examined in Limulus ventral photoreceptors by studying the effects on the light response of heparin and neomycin, agents that inhibit the production or action of IP3. Both heparin and neomycin reduce responses to brief flashes of light and the transient component of responses to steps of light, and also inhibit IP3-induced calcium release, indicating that IP3 plays a direct role in invertebrate visual excitation. The effects of BAPTA, a calcium buffer, were also examined and shown to be consistent with a role for IP3-mediated calcium release in visual excitation. However, all three agents fail to block the plateau component of the response to a step of light, indicating that a single pathway involving IP3 and calcium cannot solely be responsible for visual excitation in invertebrates. We suggest that the inositol phosphate cascade and a second parallel process that is not dependent on IP3 are involved in the production of the light response. PMID- 1905347 TI - Localization of immunoglobulin light chain mRNA expression in Hodgkin's disease by in situ hybridization. AB - In situ hybridization techniques were used to detect immunoglobulin light chain messenger RNA (mRNA) in 28 formalin-fixed, paraffin-embedded samples of Hodgkin's disease. Cocktails of biotinylated oligonucleotide probes specific for the constant regions of kappa and lambda light chain mRNA were used. None of the Reed Sternberg cells or their variants in any of the cases studied showed positive staining with either probe, in contrast to normal plasma cells which showed strong staining in the same sections. It was concluded, therefore, that the cytoplasmic immunoglobulin frequently detected within these cells by immunocytochemistry is present not as a result of synthesis, but as a result of some other mechanism. PMID- 1905345 TI - Congenital muscular dystrophy: brain alterations in an unselected series of Western patients. AB - The typical form of congenital muscular dystrophy (CMD) described in Western countries is generally considered different from its Japanese variant because of the absence of CNS involvement. Evaluations from both a clinical and a neuroradiological point of view were made of the CNS functions of 12 unselected Western children affected by CMD. In five patients, clinical observation and intelligence tests showed a mild to severe mental retardation. One of these patients suffered also from a severe form of epilepsy. In the same five patients, various degrees of white matter hypodensity, ventricular enlargement and cerebral atrophy were also detected. Similar neuroradiological abnormalities were also found in five of the seven children who did not have clinical symptoms or signs of CNS involvement. In one of these cases, necropsy neuropathological examination showed the gyral anomalies characteristic of the Japanese type of CMD. This study clearly indicates the high frequency of subclinical CNS alterations in typical Western CMD, suggesting that it should be considered a type of myoencephalopathy like its Japanese counterpart. PMID- 1905346 TI - Extracranial vertebral artery dissection following tonic clonic seizure. AB - A 34 year old woman developed cerebral infarction, following a tonic-clonic seizure. A vertebral artery dissection was demonstrated and may have been caused by arterial trauma during the seizure. This cause of morbidity following convulsive seizures may have been overlooked in the past and needs to be recognised in view of the potential benefits of anticoagulation. PMID- 1905348 TI - Low-dose interferon gamma renders neuroblastoma more susceptible to interleukin-2 immunotherapy. AB - Neuroblastoma remains a common and deadly childhood tumor, resistant to both surgical and chemo/radiotherapeutic intervention in its advanced stages. The role of immunotherapy in such cancers has yet to be defined. In previous work, we found that the addition of interferon gamma (IFN-gamma) to 3-day in vitro tissue cultures of the murine neuroblastoma C1300, led not only to the tumor's increased cell surface expression of the immunologically important major histocompatibility complex (MHC) class I antigen, but also to an increased susceptibility of such modified tumor to subsequent lymphokine activated killer (LAK) cell lysis. In this study, we sought to determine the in vivo applicability of these findings. Initial dose-response studies helped define a regimen of rIFN-gamma's administration that upregulated MHC class I without activating host natural killer (NK) activity. A/J mice bearing 7-day-old subcutaneous C1300 were randomized to receive daily morning injections of either 0, 25,000, 50,000, or 100,000 U of rIFN-gamma intraperitoneally for 6 days. Animals were killed at days 3, 6, and 9 after initiation of rIFN-gamma therapy, and tumors were excised, digested, and stained for both MHC class I and II expression. At the time of sacrifice, splenocytes from each animal were tested for NK cytotoxicity toward YAC (an NK-sensitive lymphoma) and C1300. These studies defined 3 days of therapy with 25,000 U as a "priming" dose that increased expression of class I with minimal impact on NK activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1905349 TI - [Studies on chemical protectors against radiation. XXXIII. Protective mechanisms of various compounds against skin injury induced by radiation]. AB - The radiation protective mechanisms on skin injury induced by soft X-irradiation were investigated by use of various radiation protective agents such as sulfur compounds (MEA, MEG, thiourea), nucleic acid constitutional compounds (adenosine, inosine), antioxidative compounds (sesamol, ferulic acid, ascorbic acid), crude drugs (Rosae Fructus, Anemarrhenae Rhizoma, Trapae Fructus, Forsythiae Fructus, Aloe arborescens). Scavenge action of activated oxygen, inhibitory effect of lipid peroxidation, induction of antioxidative protein and protective effect against damage of deoxyribonucleic acid and superoxide dismutase by X-irradiation were evaluated as the radiation protective mechanisms, and relationship between these results and protective effect of skin injury induced by radiation was studied. PMID- 1905350 TI - [Metabolic study on chondroitin sulfates in rabbits]. AB - The metabolic studies on three types of chondroitin sulfates in rabbits were performed. The analyses of chondroitin sulfates gave the following results concerning their metabolic behavior. 1) Desulfation of chondroitin sulfates on GalNAc C6 position was observed more clearly after the administration of low molecular weight chondroitin sulfate (molecular weight, 6000 and 16,000) than after that of high molecular weight one (molecular weight, 50,000). 2) The disappearance velocities of the administered low molecular weight chondroitin sulfates in the blood and those of excretion into the urine were faster than those of high molecular weight one. 3) Intact chondroitin sulfates were excreted into the urine after the administration of low molecular weight chondroitin sulfates, while chondroitin sulfates having more than 30000 molecular weight were not detected in the collected urine after the administration of high molecular weight one. PMID- 1905351 TI - Factors affecting the in-vitro development to blastocysts of bovine oocytes matured and fertilized in vitro. AB - The effects of media (TCM199 vs. synthetic oviduct fluid, SOF), sera (foetal calf serum, FCS vs. human serum, HS), gas atmosphere (5% CO2 in air vs. 5% CO2, 5% O2 and 90% N2) and coculture with bovine oviduct epithelial cells (cells vs. no cells) on the in-vitro development of in-vitro matured and fertilized bovine oocytes were examined. Immature oocytes surrounded with compacted cumulus cells were cultured for 24 h in TCM199 supplemented with 10% FCS, 10 micrograms follicle-stimulating hormone (FSH)/ml and 10 micrograms luteinizing hormone (LH)/ml, 1 microgram oestradiol/ml, and 1 x 10(6) granulosa cells at 39 degrees C under 5% CO2 in air. In-vitro fertilization was performed with frozen-thawed, heparin-treated (100 micrograms/ml, 15 min) spermatozoa from 2 bulls. Oocytes were incubated with 2.5 x 10(6) spermatozoa/ml for 24 h and then cultured in one of 16 treatments for 7 days. Cleavage (2-8-cell) and development to blastocysts were recorded on Days 2 and 7, respectively, after the start of culture. SOF was superior to TCM199 for cleavage (P less than 0.01), development to blastocysts (P less than 0.001) and for proportion of cultured ova resulting in blastocysts with at least 60 or at least 100 nuclei (P less than 0.001). FCS was superior to HS for development to blastocysts (P less than 0.001) and 5% oxygen was superior to air for the proportion of ova reaching at least 60 cells (P less than 0.01). For cleavage and development to blastocysts, there was an interaction between serum and cells (P less than 0.01). In the presence of cells, ova preferred FCS, in their absence, serum had little effect.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1905352 TI - Evidence that gonadotrophin surge-attenuating factor exists in man. AB - This review article summarizes the evidence provided by in-vivo and in-vitro studies suggesting that the human ovary produces a nonsteroidal factor distinct from inhibin which participates in the control of gonadotrophin secretion from the pituitary. This factor has been called gonadotrophin surge-attenuating factor (GnSAF) and is defined as attenuating the endogenous surge in luteinizing hormone (LH) in superovulated women by reducing the pituitary response to LH-releasing hormone. In-vivo bioactivity of GnSAF has been detected during the follicular phase of superovulated cycles; in-vitro studies have shown activity of this factor in human follicular fluid. From a physiological point of view, a hypothesis is proposed that GnSAF attenuates the amplitude of the positive effect of oestradiol on gonadotrophin secretion during the follicular phase of the human menstrual cycle and therefore plays an important role in controlling ovulation. If GnSAF is isolated, it may have several clinical applications including contraception. PMID- 1905353 TI - Impact of season on seminal characteristics and endocrine status of adult free ranging African buffalo (Syncerus caffer). AB - Pituitary, gonadal and adrenal activity were compared in free-living, adult African buffalo bulls during the breeding and nonbreeding seasons. Frequent blood samples were collected for 2 h from anaesthetized bulls treated intravenously with saline, gonadotrophin-releasing hormone (GnRH, 200 micrograms), human chorionic gonadotrophin (hCG, 10,000 i.u.) or adrenocorticotrophic hormone (ACTH, 1.5 mg). Electroejaculates also were collected from anaesthetized bulls during the breeding and nonbreeding seasons. Pretreatment testosterone concentrations among bulls varied more during the breeding (0.17-23.0 ng/ml) than the nonbreeding (0.15-2.21 ng/ml) season. The variation within the breeding season was attributed to 8 of 25 bulls producing higher (P less than 0.05) serum testosterone (High-T; 16.28 +/- 2.03 ng/ml) and testicular LH receptor (1.53 +/- 0.22 fmol/mg testis) concentrations compared with their seasonal counterparts (Low-T; 0.95 +/- 0.26 ng/ml; 0.38 +/- 0.04 fmol/mg) or with all bulls during the nonbreeding season (0.90 +/- 0.27 ng/ml; 0.31 +/- 0.04 fmol/mg). The magnitude of GnRH- and hCG-induced increases in serum testosterone was similar (P greater than 0.05) between Low-T bulls and bulls during the nonbreeding season. In the High-T animals treated with GnRH or hCG, serum testosterone did not increase, suggesting that secretion was already maximal. Peak serum LH concentrations after GnRH were greater (P less than 0.05) in bulls during the nonbreeding than the breeding season; FSH responses were similar (P greater than 0.05). ACTH treatment did not increase serum cortisol concentrations above the 2-fold increase measured in bulls treated with saline, hCG and GnRH (P greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1905354 TI - Pituitary and ovarian responses to luteinizing-hormone-releasing hormone during pregnancy and after parturition in brown hares (Lepus europaeus). AB - Female hares were given an i.v. injection of 5 micrograms luteinizing-hormone releasing hormone (LHRH) between Days 7 and 19 (n = 21), 20 and 33 (n = 17) and 34 and 41 (n = 17) of pregnancy, and in the 3 days after parturition (n = 16). Whatever the stage of pregnancy, the LHRH injection induced a release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) and an acute secretion of progesterone; these hormonal responses increased significantly during pregnancy, to reach values similar to those observed in nonpregnant, nonpseudopregnant females during the breeding season in the 3 days after parturition. However, the release of LH remained monophasic in pregnant and post partum females, in contrast to the unmated females during the reproductive season, in which there was a biphasic profile. The proportion of ovulating females after LHRH treatment was approximately 60% at the beginning and end of pregnancy; and, after parturition, fell to 23% between Days 20 and 33. After Day 33, the pituitary response to LHRH was significantly higher in ovulating than in nonovulating females. At the beginning of pregnancy, 67% of females aborted after LHRH injection; after Day 20, the incidence of abortion decreased significantly and was 0% from Day 34. The amplitude and duration of progesterone secretion by the new corpora lutea resulting from ovulation after LHRH injection were similar to those of corpora lutea induced in nonpregnant females during the breeding season.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1905355 TI - Interactive effects of 1-octen-3-ol and carbon dioxide on mosquito (Diptera: Culicidae) surveillance and control. AB - Responses of natural populations of biting Diptera were studied at Everglades National Park, Fla., to three levels (0, 3.0, and 41.1 mg/h) of 1-octen-3-ol (octenol), four levels (0, 20, 200, and 2,000 ml/min) of carbon dioxide (CO2), and their combinations. Catches of mosquitoes (Aedes taeniorhynchus (Wiedemann), Culex [Melanoconion]) spp., Cx. nigripalpus Theobald, and Wyeomyia spp.) and one tabanid (Diachlorus ferrugatus (F.)) were affected significantly by CO2 and octenol. Significantly greater numbers of all taxa were collected as the level of CO2 was increased. The 3.0-mg/h release rate of octenol alone resulted in increased trap catches relative to no bait for all taxa except Cx. (Melanoconion) spp., whereas the 41.1-mg/h release rate alone generally reduced trap catches relative to either no bait or 3.0 mg/h octenol. The effect of CO2 and octenol was additive for Cx. (Melanoconion) spp. and D. ferrugatus and synergistic for Ae. taeniorhynchus. Six octenol-supplemented CO2 treatments produced mixed results for Cx. nigripalpus. PMID- 1905356 TI - The role of the SOS response in bacteria exposed to zidovudine or trimethoprim. AB - Trimethoprim was more potent than zidovudine as an inducer of the SOS response in Escherichia coli. The level of induction by each compound initially increased with rising drug concentration and then fell; this effect was less marked with zidovudine than with trimethoprim. The SOS response did not appear to be involved in the inhibition of bacterial multiplication as the MICs of trimethoprim or zidovudine for recA430 and lexA3 mutants, which are unable to induce the SOS response, were identical to the MICs for the parent strains. However, the bactericidal activity of each compound against strains deficient in the SOS response was reduced. This suggest that induction of the DNA repair system contributes to the bactericidal activity of the drugs. PMID- 1905357 TI - Effect of plastic catheter material on bacterial adherence and viability. AB - The kinetics of adherence of single isolates of Staphylococcus aureus, S. epidermidis, Pseudomonas aeruginosa and Escherichia coli to catheters made of polyvinyl chloride (PVC), Teflon, siliconised latex, polyurethane and Vialon was evaluated by a radiometric assay. Radiolabelled bacteria (10(8) cfu/ml) were incubated in vials containing 1-cm lengths of catheter for up to 3 days. The peak of maximal adherence to each biomaterial was reached after 24 h for P. aeruginosa and after 72 h for the other strains. Bacterial adherence to PVC and siliconised latex was significantly higher (2-6 times; p less than 0.05) than to the other biomaterials for all the strains. The lowest values of adherence were observed with polyurethane and Vialon for the staphylococci but with Teflon for E. coli and P. aeruginosa. Bacterial viability and growth was evaluated in eluates obtained from incubation of segments of each catheter in buffer for 24 h. None of the eluates affected the viability of the staphylococci. However, all of them, significantly increased the growth of E. coli and P. aeruginosa with the exception of the eluate from siliconised latex, in which the inoculum count was reduced to an undetectable level for E. coli. We conclude that bacterial adherence to catheters may depend in part on the nature of the biomaterial and that certain substances eluted from the catheters may affect the viability and growth of different micro-organisms. PMID- 1905358 TI - The stringent response blocks DNA replication outside the ori region in Bacillus subtilis and at the origin in Escherichia coli. AB - When the Bacillus subtilis dnaB37 mutant, defective in initiation, is returned to permissive temperature after growth at 45 degrees C, DNA replication is synchronized. Under these conditions, we have shown previously that DNA replication is inhibited when the Stringent Response is induced by the amino acid analogue, arginine hydroxamate. We have now shown, using DNA-DNA hybridization analysis, that substantial replication of the oriC region nevertheless occurs during the Stringent Response, and that replication inhibition is therefore implemented downstream from the origin. On the left arm, replication continues for at least 190 x 10(3) base-pairs to the gnt gene and for a similar distance on the right arm to the gerD gene. When the Stringent Response is lifted, DNA replication resumed downstream from oriC on both arms, confirming that DNA replication is regulated at a post-initiation level during the Stringent Response in B. subtilis. Resumption of DNA synthesis following the lifting of the Stringent Response did not require protein or RNA synthesis or the initiation protein DnaB. We suggest, therefore, that a specific control region, involving Stringent Control sites, facilitate reversible inhibition of fork movement downstream from the origin via modifications of a replisome component during the Stringent Response. In contrast, in Escherichia coli, induction of the Stringent Response appears to block initiation of DNA replication at oriC itself. No DNA synthesis was detected in the oriC region and, upon lifting the Stringent Response, replication occurred from oriC. Post-initiation control in B. subtilis therefore results in duplication of many key genes involved in growth and sporulation. We discuss the possibility that such a control might be linked to differentiation in this organism. PMID- 1905359 TI - In vivo interaction of Escherichia coli lac repressor N-terminal fragments with the lac operator. AB - Escherichia coli lac repressor is a tetrameric protein composed of 360 amino acid subunits. Considerable attention has focused on its N-terminal region which is isolated by cleavage with proteases yielding N-terminal fragments of 51 to 59 amino acid residues. Because these short peptide fragments bind operator DNA, they have been extensively examined in nuclear magnetic resonance structural studies. Longer N-terminal peptide fragments that bind DNA cannot be obtained enzymatically. To extend structural studies and simultaneously verify proper folding in vivo, the DNA sequence encoding longer N-terminal fragments were cloned into a vector system with the coliphage T7 RNA polymerase/promoter. In addition to the wild-type lacI gene sequence, single amino acid substitutions were generated at positions 3 (Pro3----Tyr) and 61 (Ser61----Leu) as well as the double substitution in a 64 amino acid N-terminal fragment. These mutations were chosen because they increase the DNA binding affinity of the intact lac repressor by a factor of 10(2) to 10(4). The expression of these lac repressor fragments in the cell was verified by radioimmunoassays. Both wild-type and mutant lac repressor N termini bound operator DNA as judged by reduced beta-galactosidase synthesis and methylation protection in vivo. These observations also resolve a contradiction in the literature as to the location of the operator-specific, inducer-dependent DNA binding domain. PMID- 1905360 TI - A simple method to generate non-trivial alternate alignments of protein sequences. AB - A major problem in sequence alignments based on the standard dynamic programming method is that the optimal path does not necessarily yield the best equivalencing of residues assessed by structural or functional criteria. An algorithm is presented that finds suboptimal alignments of protein sequences by a simple modification to the standard dynamic programming method. The standard pairwise weight matrix elements are modified in order to penalize, but not eliminate, the equivalencing of residues obtained from previous alignments. The algorithm thereby yields a limited set of alternate alignments that can differ considerably from the optimal. The approach is benchmarked on the alignments of immunoglobulin domains. Without a prior knowledge of the optimal choice of gap penalty, one of the suboptimal alignments is shown to be more accurate than the optimal. PMID- 1905361 TI - Minoxidil versus nitroglycerin: a prospective double-blind controlled trial in transcutaneous erection facilitation for organic impotence. AB - A new type of topically applied drug (minoxidil) to facilitate erection is presented. Minoxidil acts directly on arterial smooth muscles via relaxation. This drug (1 ml. of a 2% solution) was studied under strict laboratory conditions in a double-blind controlled trial on 33 patients (4 with neurogenic plus arterial, 10 with neurogenic and 19 with arterial impotence) and compared to placebo and nitroglycerin (2.5 gm. of a 10% ointment). The application sites were the penile shaft (nitroglycerin) or glans penis (minoxidil and placebo). Increases in diameter and rigidity were measured with the RigiScan device and arterial flow was evaluated by conventional Doppler sonography. Side effects were considered as well. This drug proved to be more active than nitroglycerin and placebo in increasing diameter, rigidity and arterial flow of the penis. The highest activity proved to occur in neurogenically impotent patients. Fewer side effects also were found with minoxidil than with nitroglycerin. For these reasons minoxidil is proposed as a long-term therapeutic agent for organic impotence. PMID- 1905362 TI - rTPA: why do we waste these hundreds of millions of dollars? PMID- 1905363 TI - [Pediatrics in the tropics]. AB - The authors attempt to give a short review of key problems of paediatrics in tropical countries. The contribution is based on their experience with teaching and as practicing paediatricians in Ethiopia. The profound differences of background and general conditions lead to different priorities of practical work as well as of teaching students (particularly from developing countries). Basic information on the children's situation in developing countries, where the vast majority of today's children live and are immediately affected by so-called global problems, should be known to all paediatricians. PMID- 1905365 TI - [Studies on manifestations of Rh-related hemolytic disease of the newborn in the years 1974-1989 in the Erfurt district]. AB - In the course of 13 years (1977-1989) 223 of 223,121 liveborn infants in the district of Erfurt suffered from haemolytic disease due to Rh-isoimmunization, 0.1 per cent died. An initial drop of morbidity from 1.6 to 0.6 of 1000 newborns was followed by stagnation and further increase during the last years. More than 50% of the affected babies were delivered by women who had to be protected from sensibilization by immune prophylaxis. The cause for the immunization were deliveries (75%), miscarriages and interruptions (23%). The most important reason for the insufficient decrease of the Rh-morbidity is the failure of immune prophylaxis in the case of ABO-incongruence between mother and child. Our results support the demands for a general immune prophylaxis without taking into consideration the main blood groups and the number and result of the pregnancy. The quantity of severe erythroblastosis (7 stillborn and 5 hydropic liveborn) demonstrates the necessity to improve the prenatal management of these babies. PMID- 1905364 TI - [Candida parapsilosis infection as a complication of long-term parenteral nutrition]. AB - In case of short bowel syndrome in infancy the total parenteral nutrition was complicated by catheter-associated Candida parapsilosis septicemia based on generalized enterococci infection. Specific problems in antifungal treatment are discussed. PMID- 1905366 TI - [Complicated diverticulosis of the small intestine simulating perforated stomach ulcer]. PMID- 1905367 TI - Electrophysiologic evaluation of cardiovascular agents in the isolated intact rabbit heart. AB - A modification of the Langendorff perfused rabbit heart is described. This model can be used to perform electrophysiologic studies in the isolated heart and is ideally suited for acute pharmacologic evaluation. His bundle electrograms were measured with a plunge electrode and allowed atrioventricular (AV) nodal physiology to be directly and precisely evaluated. Atrial conduction and refractoriness, atrioventricular node conduction and refractoriness, His-Purkinje conduction, and ventricular conduction and refractoriness could be accurately measured. Verapamil had a depressant effect on AV nodal conduction and refractoriness without affecting His--Purkinje conduction or myocardial refractoriness. Flecainide prolonged atrial conduction and His-Purkinje conduction with less effect on AV nodal physiology. The use of this isolated perfused rabbit heart model is an inexpensive and reliable technique for the evaluation of the electrophysiologic effects of pharmacologic agents on the conduction system of the heart. A major advantage of the isolated heart model is the absence of autonomic reflexes, which can confound studies performed in intact animals. PMID- 1905368 TI - A method to maintain normal respiratory and metabolic state in artificially respired rats. AB - Analysis of arterial blood gases (ABG) in awake, paralyzed, locally anesthetized, and artificially respired rats revealed the development with time of severe hypoxemia associated with metabolic acidosis despite adequate ventilation as assessed by normal PaCO2. These respiratory and metabolic disturbances may underlie the progressive deterioration experienced with this preparation frequently used in neuropharmacological experiments. We report here that the intravascular infusion of bicarbonated artificial plasma, associated with continuous positive pressure ventilation, prevents the deterioration of the respiratory and metabolic state in this preparation, which can be maintained within the range of that of the freely moving animal. This stabilized preparation may thus be highly suitable for neuropharmacological experiments extending for several hours. PMID- 1905370 TI - Validity of the in vitro system as a correlate of the in vivo model of RadLV lymphomagnesis. AB - Adult BL/6 mice are highly sensitive to lymphomagnesis by the radiation leukemia virus variant A-RadLV (80-100% T-cell lymphoma incidence after a latency of 70 110 days). This study shows that the in vivo elimination of T-cell subsets (including suppressor and cytotoxic T-cells) achieved by the repeated administration of cyclophosphamide, cyclosporin A, anti CD4 or anti CD8 mAb shortly after virus infection did not interfere with the lymphomagenic pathway. No reduction in the high lymphoma incidence or tumor latency was observed following the different treatments. Thus the suggestion on the basis of in vitro studies that the early phase of A-RadLV lymphomagenesis is associated with suppressor T-cells which abrogate a potential anti-tumor immune response has not been confirmed in these studies. PMID- 1905369 TI - Heterogeneity of the breakpoint localization in malignant cells with a 9p11 chromosomal abnormality. AB - The p11 band of the short arm of chromosome 9 is involved in various cytogenetic alterations occurring in several malignant diseases. Using probes isolated from the 9p11 band in the study of a case of alpha-heavy-chain disease (MAL) with t(9;14)(p11;q32), we studied the DNA from seven malignant cell samples, including four cases of acute lymphoblastic leukemia with tdic(9;12)(p11;p12). Using pulsed field electrophoresis analysis we demonstrated that the breakpoints were 3-300 kb distant from the original MAL breakpoint without clustering within the subset of leukemias with the tdic(9;12). PMID- 1905371 TI - [Hemophilia. A disappearing disease?]. PMID- 1905373 TI - [Lithium and hyperparathyroidism]. PMID- 1905372 TI - [A comparative therapeutic and multicenter trial of rifampicin and doxycycline versus streptomycin and doxycycline in human brucellosis]. AB - BACKGROUND: Comparison and evaluation of the efficacy and safety of two treatment schedules in human brucellosis. METHODS: A comparative, randomized, multicentric, open study of 45 days doxycycline plus rifampin in the initial 21 days (group A) versus 45 doxycycline plus streptomycin in the initial 14 days (group B). 42 were included in each group. The diagnosis of brucellosis was based on blood culture or consistent clinical findings and a Wright's serum agglutination titer of 1/160 or greater. Clinical and laboratory monitoring was carried out, including blood cultures on the days 7 and 48 and after 3, 6, and 12 months. RESULTS: 38 patients in each group were evaluable at the end of treatment. 3 group A patients and 1 group B patient had initial therapeutic failure. 31 group A patients and 35 group B patients could be followed up during 6 months or more (mean follow up of 10.5 and 11.5 months, respectively). 9 relapses (29%) developed in group A and 2 (6%) in group B (p less than 0.05). 22 patients of the 34 finally evaluated in group A (65%) were considered as cured, versus 33 of the 36 in group B (92%) (p less than 0.01). Side effects not requiring withdrawal of the treatment developed in 12 patients, without differences between the two groups. CONCLUSIONS: In the therapy of human brucellosis, the association of doxycycline (45 days) and rifampin (21 days) is less effective than the classical association of doxycycline and streptomycin. PMID- 1905374 TI - [Towards a cheap and easily available determination of glomerular filtration rate]. PMID- 1905375 TI - [Nitrate tolerance measured by exercise test. Comparison of 2 preparations]. PMID- 1905376 TI - [The concept of lung and heart-lung preservation within the scope of multiple organ procurement]. AB - Preservation of the lung is still one of the most challenging problems, because due to limited procurement time not all organs available can be used. The most common procurement technique is flush perfusion of the pulmonary artery system. Alternative methods in clinical use are either the autologous working heart-lung preparation or donor core-cooling (DCC). The own concept presented here, modified to the special demands of multi-organ-procurement, combines DCC and interstitial equilibration adapted to intracellular ion concentration. DCC is induced by extracorporeal circulation (ECC) using a transportable heart lung machine including a highly effective cooling system: cooling circuit based on two parallel heat exchangers with ice-water cooling produced by a high-pressure overflow of a low-temperature ice block (-40 degrees C). While cooling by ECC stepwise hemodilution is achieved by priming volume and incorporation of the cardioplegic solution (Bretschneider-HTK). The aim of equilibration is to lower the extracellular levels of sodium and calcium, and to increase the level of potassium. Additionally, the buffer capacity of donor blood is increased by the incorporated histidine-buffer system (alpha-stat). To avoid donor organ edema the time of ECC should be as short as possible. Using our system donor organ temperatures below 10 degrees C are reached within less than 30 min. In addition to ECC, lung surface cooling is achieved by external overflow with cold arterial blood (internal mammary artery). Besides lung preservation the main advantage of this concept is the profound precooling of all visceral organs before their individual flush perfusion. PMID- 1905377 TI - [In situ protection of the liver with Bretschneider HTK solution]. AB - Liver resections are usually performed under occlusion of the hepatoduodenal ligament (Pringle manoeuvre) in order to limit operative blood loss. The maximal ischemic tolerance, although individually different, is generally accepted to be 60 min. Resections of centrally located tumors require precise preparation, sometimes combined with vascular reconstructions. In such cases a prolonged ischemic time is inevitable. A save prolongation of the ischemic tolerance could be useful for extensive liver resections. In an experimental study in pigs ischemic tolerance of the liver was studied under hypothermic protection with the HTK solution of Bretschneider during 2 and 3 h. Deterioration of liver function was compared with a warm ischemia during 2 h. Results showed significantly less serum transaminase activities and better hepatic blood flow (ICG test) after an ischemia under protection with the HTK solution compared to a warm ischemia during 2 h. A prolonged ischemia during 3 h under protection with the HTK solution was well tolerated. First clinical applications of hypothermic hepatic protection during resection were successful. PMID- 1905378 TI - The impact of one staff nurse's research. PMID- 1905379 TI - Refusing nutrition and hydration: the Cruzan case. PMID- 1905380 TI - Physiological and perceptual responses to cycle and treadmill exercise during pregnancy. AB - We compared physiological and perceptual responses to non-weight bearing (cycle) and weight bearing (treadmill) exercise in 16 sedentary women throughout a normal term pregnancy. Subjects were recruited late in the first trimester (less than 13 wk gestation) and were studied at 4 wk intervals throughout pregnancy and 4 wk postpartum (PP). Exercise consisted of four 5 min protocols; two were performed on the cycle (C1 = 50 W; C2 = 75 W) and two on the treadmill (T1 = 66 m.min-1, 2.5% grade; T2 = 66 m.min-1, 12% grade). Measured variables included oxygen consumption (VO2), heart rate (HR), minute ventilation (VE), and ratings of perceived exertion (RPE, 10-point Borg scale). Absolute VO2 (ml.min-1) during cycle exercise increased (P less than 0.001) by 25 wk gestation, while relative VO2 (ml.kg-1.min-1) during treadmill walking was unchanged through late pregnancy and PP. This suggests that cycle exercise is not a true non-weight bearing exercise within a given group of women throughout gestation. Subjects' VO2max values were estimated at each test interval and found to increase (P less than 0.001) by 25-28 wk gestation. Heart rate and RPE responses to exercise remained constant throughout gestation and decreased (P less than 0.01) PP. Although they did not participate in a regular exercise program, it appears that our subjects experienced a mild aerobic training effect during late pregnancy. PMID- 1905381 TI - Predicting the minimal energy costs of human walking. AB - Preferred stride frequency (PSF) of human walking has been shown to be predictable as the resonant frequency of a force-drive harmonic oscillator (FDHO). The purpose of this study was to determine whether walking at the PSF and FDHO leads to minimal metabolic and mechanical costs. Subjects walked on a level treadmill at the PSF, FDHO, and frequencies above and below. Effects of stride length (SL) and speed (S) were assessed by two conditions, one in which SL was constant and the other in which S was constant. The predictability of PSF from resonance was replicated. Walking at the PSF and FDHO frequencies resulted in metabolic costs which were not significantly different (P greater than 0.05). A U shaped oxygen consumption curve was observed with the minimum at the PSF and FDHO conditions when S was constant. A two-component curve in which a breakpoint was observed was found in the SL constant condition. A significant increase in metabolic cost was observed above the PSF/FDHO (P less than 0.01). Internal work (power) values were not significantly different between walking frequencies for the S constant condition. In the SL constant condition, internal work values showed linear increases as frequency increased. It was concluded that PSF of walking arises from the interface of the resonance properties of the limbs as oscillators and the tendency of biological systems to self-optimize. PMID- 1905382 TI - DNA damage induced by 7,12-dimethylbenz[a]anthracene in the liver and the mammary gland of rats exposed to polycyclic aromatic hydrocarbon enzyme inducers during perinatal life. AB - The long-lasting modulating effect induced by the prenatal or neonatal exposure to phenobarbital (PB) and aroclor on the genotoxic activity of 7,12 dimethylbenz[a]anthracene (DMBA) in female Sprague-Dawley rats was studied. The effect was measured as DNA damage evaluated in the liver and in the mammary gland of 55-day-old animals, 4 and 24 h after an i.g. injection of 80 mg/kg of DMBA. PB was given per os, i.g. or in drinking water to pregnant females and by i.g. only to neonates or in adult progeny. Aroclor was injected i.g. in prenatal and in neonatal life, and a second dose was given in adult life. Under these experimental conditions it was shown that DNA damage kinetics caused by DMBA are modulated by exposure to PB and, to a minor extent, by aroclor. The amount and persistence of DNA damage were highest when PB was administered to neonates. An average 2-fold increase in the elution constants (K) of DNA in the liver and the mammary gland was observed 4 h after DMBA treatment, as compared to uninduced animals. Repeated enzyme induction by PB seems to reduce DMBA genotoxicity, as shown by a decrease in DNA damage and persistence in the liver and mammary gland. The inducibility of the monooxygenase enzyme system in perinatal life favouring metabolic activation or inactivation of polycyclic aromatic hydrocarbons might be critical in determining individual susceptibility of adult progeny to chemical carcinogenesis by DMBA. PMID- 1905383 TI - L-threonine as a symptomatic treatment for amyotrophic lateral sclerosis (ALS). AB - ALS is a fatal, neurological disease of unknown origin with no present cure. A recent pilot study has shown that L-threonine, an essential amino acid, may be effective in the symptomatic treatment of ALS. Relevant information discussing the potential role of L-threonine in the treatment of ALS is presented. PMID- 1905384 TI - Measuring and modifying hospital drug use. AB - OBJECTIVE: Various methods are available to quantitate medicinal drug use in hospitals. These represent a hierarchy of clinical specificity, complexity and cost of acquisition. Similarly, various strategies and methods are available to modify prescribing patterns. The objectives of this study are to illustrate these processes of measurement of drug use and modification of prescribing patterns using specific examples derived from practice at three major Australian teaching hospitals over 15 years. DESIGN, SETTING, MAIN OUTCOME MEASURES: Methods to measure and modify drug usage in the three hospitals are outlined and 12 examples are presented by specific drug or drug category. Each example includes details of the methods used to detect inappropriate drug use (pharmacy purchases, pharmacy issues, prescription analysis, clinical record review, performance and outcome assessment), the intervention strategies used (re-educative, persuasive, facilitative, power), the methods employed to alter drug prescribing and the relative effectiveness and cost-efficiency of the interventions. RESULTS: Readily available, relatively cheap quantitative methods provide significant information and an efficient basis for planning definitive studies, and substantial modification of prescription patterns is possible through the strategic use of limited manpower and resources. PMID- 1905385 TI - Branhamella (Moraxella) catarrhalis: pathogenic significance in respiratory infections. AB - OBJECTIVES: To assess the pathogenic significance of Branhamella catarrhalis isolates in patients with respiratory infections and to define the clinical characteristics of such patients. DESIGN AND SETTING: Respiratory specimens were assessed in a three-year prospective study performed in a Brisbane metropolitan hospital. Assessment of the pathogenic significance of isolates of B. catarrhalis was based on four predetermined criteria: (i) clinical evidence of respiratory infection based on history, examination and chest x-ray; (ii) isolation of B. catarrhalis as the sole potential pathogen; (iii) absence of antibiotic treatment in the previous two weeks; and (iv) subsequent clinical response to an antibiotic to which the isolate was sensitive. RESULTS: B. catarrhalis was identified in 118 respiratory samples, 92 (78%) being from patients less than 10 years old. Infection with B. catarrhalis was more commonly seen in winter months and was community-acquired in two-thirds of cases. Isolation of this organism was associated with a broad variety of upper and lower respiratory tract syndromes. Isolates were considered to be of pathogenic significance (all four above criteria satisfied) in 35% of cases and of possible significance (the first and fourth criteria satisfied) in a further 15% of cases. Isolates were more likely to be of pathogenic significance in older patients and in those with pre-existing cardiorespiratory disease; however, a number of serious infections were observed in previously-well children. Expectorated sputum and tracheal aspirates were more likely to yield a clinically significant isolate than nasopharyngeal aspirates. Production of beta-lactamase was demonstrated in 88% of isolates. CONCLUSION: B. catarrhalis causes respiratory infection more frequently than is generally appreciated. Isolation of this organism from the respiratory tract had pathogenic significance or possible pathogenic significance in 50% of our patients. If therapy is indicated in patients with respiratory infection caused by this organism, traditional beta-lactam regimens cannot be relied upon, as shown by the high rate of beta-lactamase production in this study; a tetracycline, erythromycin, a second or third generation cephalosporin, or the combination of a penicillin derivative and beta-lactamase inhibitor should be considered. PMID- 1905386 TI - [Brain circulation in residual cerebral damage. A Doppler ultrasound study]. AB - Transcranial Doppler recordings of flow velocities in 5 cerebral arteries were performed in children with cerebral palsy or with focal epileptic discharges. In 22 children with severe bilateral cerebral palsy as an average the flow velocities were 55% of the norm. In 8 of 10 children with spastic hemiplegia, the velocities were reduced at least in one artery of the affected side. 7 of 11 children with a mixed focus and 4 of 18 children with a pure epileptic focus in the EEG presented reduced velocities within the artery belonging to the focus. The results and other studies indicate a reduced cerebral blood flow in severe cerebral palsy with may be caused by vascular, metabolic, bioelectric or pharmacologic factors. PMID- 1905387 TI - A case of postanoxic encephalopathy with cortical action and brainstem reticular reflex myoclonus. AB - A patient with postanoxic encephalopathy, with both action- and stimulus sensitive reflex myoclonus, is described. The action myoclonus was multifocal and cortical in origin. In contrast, reflex myoclonus elicited by somaesthetic and auditory stimulation was generalised. The earliest reflex electromyograph activity was recorded in the sternocleidomastoid; myoclonic activity then spread up the brainstem and down the spinal cord, suggesting that this reflex myoclonus had its origin in the caudal brainstem. Stimulus sensitivity was greatest in the limbs. The bulbospinal motor pathways involved in the generalised reflex myoclonus were rapidly conducting, and this characteristic distinguishes this form of brainstem reflex myoclonus from that described in hyperekplexia. PMID- 1905388 TI - Tumor necrosis factor and c-fos expression in human peripheral-blood monocytes: expression is dependent on stage of in vitro differentiation. AB - The differentiation of monocytes and macrophages both in vitro and in vivo can be characterized by the modulation of specific functional and molecular phenotypes. We have determined in human peripheral-blood monocytes (HPBM) the role of in vitro differentiation on the expression of nonspecific tumoricidal activity, induction of soluble tumor necrosis factor (TNF) activity and TNF-specific mRNA transcription. HPBM were activatable by bacterial lipopolysaccharide (LPS; 1 microgram/ml) for nonspecific cytotoxicity to A375M (human malignant melanoma cell line) only during the first 24 h of in vitro differentiation. Activated supernatants of HPBM were found to be partially neutralizable (75 +/- 7%) by rabbit polyclonal anti-TNF antibody and, in freshly isolated HPBM, the release of soluble TNF activity determined by the L929 assay was found to occur only after activation with LPS. Maximal TNF release occurred at 8 h of LPS stimulation, and required both protein and RNA synthesis as evidenced by the ability of both actinomycin D and cycloheximide to inhibit its release. Neither control untreated HPBM nor recombinant interferon-gamma (rIFN-gamma; 1 U/ml)-treated HPBM alone released soluble TNF activity. Further in vitro culture determined that HPBM were activatable for TNF release out to 72 h of culture after which HPBM became resistant to LPS-mediated TNF release. The expression of TNF and c-fos mRNA was also determined during in vitro differentiation. Both TNF and c-fos mRNA were expressed in freshly isolated HPBM, and returned to baseline by 24 h of in vitro culture. Treatment of HPBM with LPS induced TNF transcription as late as 5 days of in vitro culture with maximal induction occurring during the first 48 h. rIFN gamma significantly induced TNF transcription at 24 h in the absence of soluble TNF activity, but did not increase transcription at later times. The expression of nonspecific cytolytic activity, the release of soluble bioactive TNF and the induction of TNF and c-fos mRNA are regulated in HPBM by differentiation determined processes. PMID- 1905389 TI - The aluminum content of parenteral solutions: current status. AB - Aluminum contaminates several chemical compounds that are administered intravenously to patients. The most highly contaminated are calcium and phosphate salts, followed by albumin and heparin. Parenteral administration of aluminum bypasses the gastrointestinal tract, which serves as a protective barrier to aluminum entry into the blood. In the past, parenteral administration of aluminum as a contaminant of water used in hemodialysis and of casein hydrolysate, the former source of protein in parenteral nutrition solutions, was associated with a low-turnover osteomalacic bone disease and, in the case of uremic patients, encephalopathy. Groups currently at risk for aluminum accumulation in tissue resulting from parenteral administration include premature infants receiving long term parenteral nutrition and patients receiving plasmapheresis therapy with albumin. Both groups may develop metabolic bone disease; the pathogenesis may involve aluminum. The Food and Drug Administration is currently considering regulation of aluminum in fluids used for parenteral nutrition. No changes are presently proposed with regard to albumin. PMID- 1905390 TI - [Treatment of glycogen storage diseases]. AB - This overview shows the present state of the art in the treatment of glycogen storage diseases (GSD) illustrated by some characteristic courses of glucose-6 phosphatase deficiency (GSD type I) and of phosphorylase b-kinase deficiency (GSD type VIa). In the majority of our patients suffering from GSD type I the combination of nocturnal gastric drip feeding (GDF) using oligosaccharides with frequent daytime meals using high amounts of glucose, it's polymers and low amounts of uncooked starch is better accepted and more effective than a round the clock diet using high amounts of uncooked starch without the use of GDF. In one of three patients suffering from GSD type VIa dextro-thyroxine has been shown to be very effective concerning linear growth velocity, liver size, hyperlipidaemia and hypertransaminasaemia. Finally, the need and availability of prenatal diagnosis is discussed in view of the rather limited therapeutical efficacy in most of the GSD. PMID- 1905391 TI - [Empty sella syndrome in childhood]. AB - 6 cases of the primary empty sella syndrome, 5 boys and 1 girl aged from 1 to 22 years, are being treated. The patients became suspicious due to a deficiency of pituitary hormones, whereby a lack of growth hormone was most common. 5 patients were short of growth; in provocative tests all 6 children showed either a partial or a complete deficiency of growth hormone. 2 patients had secondary hypothyroidism, 2 hypogonadotropic hypogonadism. Sceletal maturation was retarded between 2/12 and 4 4/12 years in all cases. All patients underwent a skull roentgenogram. An enlargement of the sella turcica was found in the case of one boy only. The findings of the other 5 children were inconspicious. For all patients the diagnosis was testified by a cranial computer-tomography. PMID- 1905392 TI - [Penoscrotal hypospadias with XXYY chromosome pattern]. AB - This is the report of a boy, 2 years and 4 months of age who presented with an penoscrotal hypospadia with normal appearing testes. Physical examination and routine laboratory tests revealed--besides a broad base of the nose and clinodactyly--no abnormality. The boy exhibits a normal speech development with retarded global intellectual development. Investigation of the hormon status revealed a disturbance of testosteron secretion and a hypergonadotropic hypogonadism. Chromosomal analysis in lymphocyte cultures revealed a XXYY karyotyp. This chromosomal pattern is seen in 3% of patients with Klinefelter syndrom; the estimated frequency is 1 in 25,000 population. A combination of an XXYY chromosomal pattern with a penoscrotal hypospadia has not been reported in the literature so far. PMID- 1905393 TI - Intergenerational equity and public spending. PMID- 1905394 TI - A human Lactobacillus strain (Lactobacillus casei sp strain GG) promotes recovery from acute diarrhea in children. AB - To determine the effect of a human Lactobacillus strain (Lactobacillus casei sp strain GG, Gefilac) on recovery from acute diarrhea (82% rotavirus), 71 well nourished children between 4 and 45 months of age were studied. After oral rehydration, the patients randomly received either Lactobacillus GG-fermented milk product, 125 g (10(10-11) colony-forming units) twice daily (group 1); Lactobacillus GG freeze-dried powder, one dose (10(10-11) colony-forming units) twice daily (group 2); or a placebo, a pasteurized yogurt (group 3) 125 g twice daily; each diet was given for 5 days, in addition to normal full diet otherwise free of fermented dairy products. The mean (SD) duration of diarrhea after commencing the therapy was significantly shorter in group 1 (1.4 [0.8] days) and in group 2 (1.4 [0.8] days) than in group 3 (2.4 [1.1] days); F = 8.70, P less than 0.001. After rehydration, each dietary group maintained a positive weight trend. The urinary lactulose-mannitol recovery ratios (means [95% confidence intervals]) on admission were 0.09 (0.03, 0.24) in group 1, 0.12 (0.07, 0.22) in group 2, and 0.08 (0.04, 0.18) in group 3; no significant alterations in intestinal permeability were observed at retesting after 2 days of realimentation. The result indicates that early nutritional repletion after rehydration causes no mucosal disruption and is beneficial for recovery from diarrhea. It is further suggested that Lactobacillus GG in the form of fermented milk or freeze-dried powder is effective in shortening the course of acute diarrhea. PMID- 1905395 TI - [Diagnostic value of detection of blood levels of lactate, pyruvate and 2,3 diphosphoglycerate in children with diabetes mellitus]. AB - Measurements were made of lactate, pyruvate and 2,3-diphosphoglycerate in 69 children admitted to the hospital in a state of diabetic ketoacidosis of different intensity. Depending on the intensity of metabolic abnormalities, the content of lactate and pyruvate was found to be increased, whereas that of 2,3 diphosphoglycerate to be lowered. Measurements of the content of lactate and the lactate/pyruvate ratio enables carrying out differential diagnosis between the ketoacidotic and lactacidotic varieties of diabetic coma. PMID- 1905396 TI - [Development of intestinal biocenosis in healthy and sick newborn infants]. PMID- 1905397 TI - Luminal glucose enhances transepithelial Na+ and fluid transports in rat lungs. AB - The effects of luminal glucose on transepithelial Na+ and fluid transports were investigated in rat lungs. Two preparations were used: isolated, perfused lungs and lungs in situ perfused with blood (cross-circulations), a situation more comparable to that existing in vivo. Unidirectional (efflux from air spaces, J(out)) and net (Jnet) Na+ fluxes and fluid absorption from air spaces were estimated in lungs filled with bicarbonate-buffered solutions containing 10 mmol/l of either mannitol, glucose or alpha-methyl-D-glucopyranoside, or 0.1 mmol/l phlorizin in the presence of glucose. In the presence of mannitol J(out) was estimated to be 7.8 +/- 1.02 pmol cm-2 s-1 in isolated lungs and 9.2 +/- 0.97 pmol cm-2 s-1 in lungs in situ, and Jnet 1.0 +/- 0.33 and 2.5 +/- 0.35 pmol cm-2 s-1, respectively. When glucose replaced mannitol J(out) (+ 30% + 40%), Jnet (+200% + 300%) and fluid absorption (+ 100% + 400%) were enhanced in both preparations. Substituting methyl glucoside for mannitol increased Na+ and fluid absorption rates to the same extent as glucose. Phlorizin, in the presence of glucose, reduced Na+ and fluid transports to values similar to those observed in the presence of mannitol. These changes did not result from modifications of the paracellular permeabilities (assessed with [3H]mannitol).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1905398 TI - Effects of environmental conditions on mitochondrial-rich cell density and chloride transport in toad skin. AB - Chloride flux across amphibian skin is usually passive, yet largely conductive; previous reports have suggested that aldosterone influences this pathway. The conductive Cl- pathway and its regulation were examined further, across the abdominal skin of toads (Bufo marinus) adapted to various environments. Short circuit current (Isc), total conductance (Gt) and Cl- influx (JCl) were measured in conditions such that there was net Cl- movement in absence of Na+ transport. In salt-deprived animals compared to salt-adapted ones, there was a significant increase in JCl (563 vs 200 pmol cm-2 s-1), aldosteronaemia (4.2 vs 1.1 nmol/l), as well as MRC density (1458 vs 851 mm-2). After adaptation to dilute Na2SO4 compared to MgCl2, JCl (631 vs 313 pmol cm-2 s-1) as well as the density of mitochondria-rich cells (MRC) (1306 vs 710 mm-2) practically doubled, while the toads' aldosteronaemia was lower (2.4 vs 10.8 mmol/l). In all groups of toads, JCl was matched by Isc, and there was a close correlation between Gt and JCl (r = 0.96), which confirms the conductive nature of transepithelial Cl- movement. Furthermore, the relationship between JCl and MRC density (r = 0.75) argues in favour of a role played by MRC on Cl- conductance of epithelial such as amphibian skin. As aldosterone injected for 1 week into NaCl-adapted toads did not influence MRC density and as aldosteronaemia was not correlated with Cl- conductance, this hormone does not emerge as the determinant of these parameters. PMID- 1905399 TI - The genomic organization of immunoglobulin VH genes in Xenopus laevis shows evidence for interspersion of families. AB - The complete genomic sequences of Xenopus laevis immunoglobulin heavy chain variable region (VH) genes comprising families IV-XI are reported. Using VH family-specific probes, linkage relationships for Xenopus VHI-VHXI have been determined. With the possible exceptions of VHIII and VHVII, Xenopus VH genes appear to be interspersed. When from two to five VH segments are identified in individual clones, the elements are found to be in the same relative transcriptional orientation. Although the relationships of promoter sequences, including the regulatory octamer, resemble those seen in other vertebrate VH genes, several Xenopus VH families are associated with additional 5' octamer sequences and octamer-like motifs. The similarities between the genomic organization of VH genes in Xenopus and higher vertebrates, indicate an early phylogenetic emergence of the mammalian-type of gene organization and regulation. PMID- 1905400 TI - Lack of a requirement for strict rotational alignment among transcription factor binding sites in yeast. AB - The MF alpha 1 gene of Saccharomyces cerevisiae is an alpha specific gene whose expression is regulated by two upstream activation sites (UASMF alpha 1S), which are the binding sites for activator proteins, MAT alpha 1 and MCM1. UASMF alpha 1 elements act in a synergistic fashion; lack of either element causes reduced expression levels that are 6- to 45-fold less than that of intact promoter in alpha cells. We investigated the effect of manipulating rotational alignments among transcription factor binding sites of MF alpha 1 on the expression of the gene. The expression level of MF alpha 1 decreased with the spacing between the two UASMF alpha 1S and no synergism was observed when the distance of the two elements was longer than 90 base pairs. No strict rotational alignment was required for their synergistic action. We also show that the spacing between UASMF alpha 1 elements and TFIID binding site, the TATA box, had little, if any, effect on MF alpha 1 expression. We chose a sufficient number of positions for UASMF alpha 1S to ensure that, in several of these positions, MAT alpha 1 and MCM1 were on the opposite side of the DNA helix with respect to the TATA box. PMID- 1905401 TI - Inactivation of Tetrahymena rRNA self-splicing by cis-platin proceeds through dissociable complexes. AB - The anti-cancer drug cis-diamminedichloroplatinum (II) (cis-DDP) reacted with Tetrahymena self-splicing rRNA ribozyme, causing loss of self-splicing activity and formation of a number of platinated RNA species. The formation of one distinct platinated product, migrating at an apparent size of 2400 nt, was closely associated with ribozyme inactivation. This platinated RNA was resistant to T1 ribonuclease digestion, suggesting the presence of inter-strand Pt cross links. The reaction rate of cis-DDP with the ribozyme followed first order kinetics and showed a saturation effect with increasing cis-DDP concentration, characteristic of an affinity-label type of interaction rather than bimolecular collision. The apparent KI for binding of cis-DDP to the ribozyme was 62 microM. Ribozyme treated with urea was not inactivated by cis-DDP, indicating that the native structure of the RNA is required for reaction with cis-DDP. Mg++, which binds to the ribozyme and causes conformational changes in the molecule, protected the ribozyme from inactivation by cis-DDP and also prevented the formation of platinated RNA. These results suggest that binding of cis-DDP to sites formed by certain secondary or tertiary structural elements of the RNA enhance the rate and the specificity of reaction of the reagent with the ribozyme. PMID- 1905402 TI - [Non-A, non-B hepatitis--epidemiologic and clinical aspects]. AB - In the years 1986-90 530 consecutive patients with acute hepatitis were hospitalized in the Department of Hepatology of the Institute of Infectious and Parasitic Diseases in Warsaw. Hepatitis A was diagnosed in 34 cases (6.4%), hepatitis B in 436 (82.3%), CMV infection in 5 (0.9%) and 55 cases (10.4%) were classified as hepatitis non-A, non-B. In 47 cases (85%) of non-A, non-B hepatitis in 8 (15%) the source of infection was unclear. In 50% of patients with parenteral exposure transaminases remained elevated for longer than 6 months, while all patients with no known exposure recovered. PMID- 1905403 TI - Differential antiproliferative activities of alpha- and gamma-interferon and tumor necrosis factor alone or in combinations against two prostate cancer xenografts transplanted in nude mice. AB - We have investigated the antiproliferative effects of recombinant human alpha- and gamma-Interferon (IFN) and recombinant human Tumor Necrosis Factor alpha (TNF) against the hormone-independently growing PC3 and DU145 prostatic tumor lines. Subcutaneous, peritumoral administration of the drugs was started 24 hours after subcutaneous implantation of 1-2 mm3 tumor pieces. IFN was given three times per week and TNF five times per week. IFN-alpha (dose-range 0.5-5 ng/gram bodyweight) had significant growth-inhibiting effects against the PC3 tumor, but showed no significant antitumor effects against the DU145 tumor. IFN-gamma monotherapy (dose-range 8-80 ng/gram bodyweight) was less effective than IFN alpha. 500 ng/gram TNF produced growth inhibition of both tumors, whereas the lower dose (50 ng/g) was only effective against the PC3 tumor. IFN-alpha and gamma combination treatment had significant antiproliferative effects against the PC3 tumor, but not against the DU145 tumor. Combinations of IFN-alpha and TNF were very effective against both xenografts; some combinations resulted in complete growth inhibition. IFN-gamma and TNF combinations also showed significant antitumor effects against both tumor lines. We therefore conclude that cytokine combination treatment may provide a new approach in the treatment of hormone-escaped prostatic tumors. PMID- 1905404 TI - An oral treatment for lead toxicity. AB - Chronic lead poisoning has traditionally been treated by parenteral agents. We present a case where a comparison of ethylene diaminetetra-acetic acid was made with 2,3-dimethyl succinic acid (DMSA) which has the advantage of oral administration associated with little toxicity and appeared to be at least as efficacious. PMID- 1905405 TI - A typhus-like illness caused by acute HIV seroconversion. AB - A patient is described in whom an acute human immunodeficiency virus seroconversion illness occurred following a trip to southern Africa. The presentation was strikingly similar to that of African tick typhus and could only be distinguished by serological testing. PMID- 1905407 TI - Glucuronidation of 7-hydroxy-4-methylcoumarin by microsomes from normal and diseased human livers. AB - Glucuronidation of 7-hydroxy-4-methylcoumarin (7-H-4-MC) by microsomal UDP glucuronosyltransferases from 12 human liver biopsy samples was studied. Glucuronidation rates were highest for livers with mild cholestasis while those for livers with mild fatty changes were similar to normal livers. The lowest rates were exhibited by livers showing primary or metastatic carcinoma on histological examination. Thus, glucuronidation of not only bile acids but also of other substrates such as 7-H-4-MC may be elevated in cholestasis. These results are also consistent with other studies stating that glucuronidation might be spared in certain mild hepatic diseases. PMID- 1905408 TI - [Morphology of the secondary capsule in hip joint endoprostheses and significance of substance abrasion. A study of autopsies]. PMID- 1905406 TI - Mechanisms of hydroperoxide-induced broncho- and vasoconstriction in isolated and perfused rat lung. AB - The mechanisms of hydroperoxide-induced broncho- and vasoconstriction were investigated in the perfused and ventilated rat lung. Hydrogen peroxide (500 microM), tertiary butylhydroperoxide (500 microM) and arachidonic acid (100 microM) induced similar profiles of broncho- and vasoconstriction which could be prevented by the inhibitor of cyclooxygenase, diclofenac (100 microM) but not by nordihydroguaiaretic acid (5 and 25 microM), an inhibitor of lipoxygenase. The hydroperoxides also caused a time-dependent increase in the levels of thromboxane and prostacycline, products of cyclooxygenase. Furthermore, the thromboxane agonist, U44069 (100 pmoles), caused a very rapid broncho- and vasoconstriction that was preventable by the thromboxane antagonist L655.240 (1 microM). L655.240 also inhibited hydrogen peroxide-induced broncho- and vasoconstriction. The phospholipase A2 inhibitors, quinacrine (100 microM) and dibucaine (100 microM), did not prevent hydroperoxide-induced broncho- and vasoconstriction. The Ca2+ chelator, EGTA, prevented hydroperoxide and arachidonic acid-induced lung constriction, although it did not inhibit the release of thromboxane. The infusion of arachidonic acid and hydroperoxides resulted in edema in the lung which was prevented by prior administration of diclofenac, indomethacin or L655.240. These results indicate that hydroperoxide-induced broncho- and vasoconstriction and lung edema are mediated by thromboxane, a product of cyclooxygenase. The mechanism of hydroperoxide-induced release of arachidonic acid is not clear but does not seem to involve Ca2+ nor the activation of phospholipase A2. PMID- 1905409 TI - 2-Bromolisuride, an ergot derivative, with dopamine antagonistic and serotonin agonistic properties. AB - The open-field test was used to study the involvement of dopaminergic and serotonergic mechanisms in the effects of 2-bromolisuride on locomotor activity in the rat. 2-Bromolisuride produced a dose-dependent inhibition of spontaneous locomotor activity. This is most likely due to an antagonistic action at postsynaptic dopamine receptors. Low doses of 2-bromolisuride potentiated apomorphine-induced hypermotility. This potentiating effect was not mediated by a blockade of presynaptic dopamine receptors, because it was not prevented by 6 OHDA lesion of the nucleus accumbens. The potentiating effect of 2-bromolisuride was completely blocked by the serotonin antagonists cyproheptadine and ritanserin. It is suggested that 2-bromolisuride possesses dopamine antagonistic and serotonin agonistic properties. PMID- 1905410 TI - The effects of the TRH metabolite cyclo(His-Pro) and its analogs on feeding. AB - Cyclo(His-Pro), or cHP, is a putative metabolite of thyrotropin-releasing hormone (TRH), and, like TRH, can inhibit food intake but requires higher doses. In attempts to improve the anorectic effects of cHP through modification of its structure, a number of its analogs were synthesized. These analogs or cHP itself were administered to rats either by intracerebroventricular (ICV) infusion or systemic injection, and their effects on food intake were measured. None of the synthetic analogs was more potent than cHP, although several analogs demonstrated comparable potencies to the parent compound. Interestingly, one cHP analog reversed the suppressive effect and stimulated feeding. This reversal, as well as the preservation of the anorectic effect by some but not all the analogs, suggests that the cHP effect on feeding does require specific structural features. PMID- 1905411 TI - Glucuronidation and sulfation in subcellular fractions and in the isolated perfused rabbit lung: influence of ethanol. AB - Glucuronidation and sulfation of 1-naphthol, 7-hydroxycoumarin, 4-nitrocatechol and phenolphthalein were studied in rabbit lung and liver. Pulmonary UDP glucuronyltransferase and sulfotransferase activities in subcellular fractions were approximately 20-50% of those determined in the liver. Ethanol did not markedly induce these enzymes in either tissue. Glucuronidation and sulfation of 1-naphthol and 7-hydroxycoumarin were also studied in the isolated perfused rabbit lung as an intact cell model. Neither glucuronidation nor sulfation of 1 naphthol was observed. The absence of conjugate formation was due neither to the presence of beta-glucuronidase and/or sulfatase, nor to alternative biotransformation pathways. About 35% of the initial 7-hydroxycoumarin was conjugated, the majority being sulfate conjugate (14.4 nmol/h) with only minor amounts (0.12%) of the glucuronide. These results indicate the importance of studying both whole organ and in vitro metabolism. PMID- 1905412 TI - Physiological and cytotoxic effects of Ca(2+) ionophores on Caco-2 paracellular permeability: relationship of 45Ca(2+) efflux to 51 Cr release. AB - The human intestinal cell line, Caco-2, and the Ca2+ ionophores, A23187 and ionomycin, were used to determine the interrelationships of 45Ca(2+) efflux, transepithelial electrical resistance (Rt), and [3H]-mannitol flux to changes in 51Cr release and lactate dehydrogenase (LDH) activity. Treatment of Caco-2 monolayers with ionomycin at concentrations of between 0.25 and 2.50 mumol/l showed similar 45Ca(2+) efflux rate constants and coefficients. Analysis of the control and ionomycin-induced 45Ca(2+) efflux values showed the data to best fit a three Ca(2+) compartmental model. All changes in Caco-2 Rt and [3H]-mannitol flux were reversible with no significant increases in 51Cr release with ionomycin concentrations of less than or equal to 2.5 mumols/l. Caco-2 monolayers treated with ionomycin at concentrations of between 5.0 and 50.0 mumols/l showed rapid non-exponential 45Ca(2+) effluxes with irreversible changes in Rt, [3H]-mannitol flux, and significant increases in 51Cr release. There was no changes in media LDH activity using either ionomycin or A23187 at concentrations of up to 50 mumols/l for 60 min. The results of our study show that: (1) disruption of Ca(2+) homeostasis in Caco-2 cells will occur with the addition of Ca(2+) ionophores at concentrations of greater than 2.50 mumols/l; (2) high concentrations (greater than 2.5 mumols/l) of ionomycin will cause non-exponential 45Ca(2+) efflux rates with irreversible changes in intracellular Rt and 14C-mannitol flux, and (3) early signs of Ca(2+) ionophore-induced damage can be detected by 51Cr release from Caco-2 cells into the media and not by changes in LDH media activity. PMID- 1905413 TI - [Comment on the article: "Occupationally-induced HIV infection in medical personnel" by J. Gruner]. PMID- 1905414 TI - The regulatory functions of CD4+ and CD8+ T-cell subsets in immune class regulation. PMID- 1905415 TI - Resident glomerular cells in glomerular injury: endothelial cells. PMID- 1905416 TI - Arachidonic acid metabolites in glomerular immune injury. PMID- 1905417 TI - Using routinely collected data for clinical research. AB - Clinical research involving prospective data collection in randomized controlled trials is not always feasible. Increasingly, hospitals are developing large clinical databases that are waiting to be mined. We have developed a computer program, ClinQuery, that facilitates such exploration and analysis. We have also shown in a series of studies that the use of clinical data is a powerful tool in health services research. In some cases, we have shown that coded data are inaccurate and that alternative clinical data are preferable. In other cases, a combination of clinical data and coded discharge diagnoses is preferable. PMID- 1905418 TI - Helping cancer patients fight infection. PMID- 1905420 TI - Clinical, serological, and immunogenetic studies of systemic sclerosis. PMID- 1905419 TI - [Detection of anti-Ro(SS-A) by using immunoimprint. Comparison with double diffusion in agar. Apropos of a series of 63 primary Gougerot-Sjogren syndromes]. AB - Among soluble anti-nuclear antigen auto-antibodies, anti-Ro(SS-A) were, for unknown reasons, difficult to detect by immunoimprint (II). The aim of this study was the development of a method of preparation of Ro(SS-A) antigen enabling greater sensitivity in the detection by II of the corresponding antibodies, then application of this method in a series of 63 cases of primary Sjogren's syndrome in order to study the clinical significance of anti-Ro(SS-A) antibodies. Ro(SS-A) antigen was prepared from human spleen and partially purified on DE-52 resin. The protein extract prepared reacted in II with reference anti-Ro(SS-A) and anti La(SS-B) antibodies. The series of 63 cases of primary Sjogren's syndrome (57 F, 6M) included 50 of extraglandular primary Sjogren's syndrome and 13 of isolated glandular primary Sjogren's syndrome. Twenty two cases of primary Sjogren's syndrome had anti-Ro(SS-A) (35%). Twenty patients had anti-Ro(SS-A) by II (32%) and 17 by double diffusion in agar (27%) (p = NS). Among 7 discordant sera, 2 were not detected by II. The incidence of anti-Ro did not differ statistically between the extraglandular (40%) and glandular (15%) primary Sjogren's syndrome groups. Patients were divided into two groups according to whether they did (n = 22) or did not (n = 41) produce anti-Ro(SS-A).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1905422 TI - [Inhibition of thrombocyte function by non-steroidal anti-rheumatic agents: a comparative study between diclofenac, acemetacin, mefenamic acid and ibuprofen]. AB - Non-steroidal antiinflammatory drugs (NSAID) interfere with the synthesis of prostaglandins by inhibiting cyclooxygenase. In blood platelets, this leads to a lack of thromboxane synthesis comparable to the congenital defect which is known to be associated with enhanced bleeding tendency, although the bleeding time may not be prolonged. The four NSAID diclofenac, acemetacin, ibuprofen, and mefenamic acid administered to healthy volunteers at the recommended dosage led to significant suppression of thromboxane synthesis; this effect was more pronounced with acemetacin and ibuprofen than with diclofenac. After intake of NSAID enhanced bleeding during surgery must be expected; in individuals with additional impairment of the hemostatic system (i.e. treatment with oral anticoagulants, mild haemophilia, von Willebrand's disease, mild thrombocytopenia), spontaneous bleeding may occur. PMID- 1905421 TI - [Ovarian hyperstimulation syndrome]. AB - The ovarian hyperstimulation syndrome is the most serious complication following ovulation induction. It is assuming greater clinical importance now that the indication for ovulation induction is no longer limited to anovulatory women but expands to other infertility problems. In its most severe manifestation the ovarian hyperstimulation syndrome consists of massive ovarian enlargement with multiple cysts, hemoconcentration, ascites, and pleural and pericardial effusion. There is no specific treatment and a reduction in the incidence of this iatrogenic syndrome can be achieved only by preventive measures. PMID- 1905423 TI - [Evaluation of short-term hospitalization in the improvement of specialized aid to children with bronchial asthma]. AB - The programmes of allergological examination and individual bronchospasmolytic therapy in children with severe asthma are discussed. These programmes are being realized at specialized departments of allergology where patients stay for two or three days during day-time. The catamnestic efficacy of such programmes is illustrated. PMID- 1905424 TI - [The role of peripheral vasodilators in the treatment of congestive heart failure in chronic cor pulmonale]. PMID- 1905425 TI - Biochemical analysis of class I and class II MHC antigens in cynomolgus macaques by one-dimensional isoelectric focusing. AB - To obtain a better estimate of major histocompatibility complex (MHC) polymorphism in the Old World macaque, Macaca fascicularis, class I and class II MHC proteins from 42 animals were analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and one-dimensional isoelectric focusing (1D-IEF). The panel represented both related and unrelated animals with a total of at least 30 serologically distinct haplotypes. Cells were sequentially immunoprecipitated with monoclonal antibody (mAb) W6/32 for class I and with mAb L243 for class II molecules, followed by neuraminidase treatment. Both sets of immunoprecipitates yielded 5-7 major bands on IEF. All bands present in offspring were present in at least 1 parent. Siblings which were serologically identical for class I and which were non-stimulatory in mixed lymphocyte culture (MLC) yielded identical IEF patterns for both class I and class II; in other sibling pairs which were serologically identical for class I antigens (Ag), IEF produced convincing evidence that the siblings were indeed nonidentical, or helped to verify that recombination had occurred within the MHC. Specific bands were found which correlated with class I specificities A8, A24, and B25 previously defined by serology. Comparison of serological and biochemical data will broaden our understanding of the MHC in Macaca fascicularis and will increase the potential use of this species in transplantation research, as a model of disease, and for comparative studies. PMID- 1905426 TI - Transfected trophoblast-derived human cells can express a single HLA class I allelic product. AB - The human trophoblast-derived JAR cell line, that does not express polymorphic HLA class I antigens even after IFN induction, can be stably transfected by genomic clones encoding the entire HLA-A2, -A3 and -B7 alpha-chain genes. The transfected genes were expressed at the cell surface in association with endogenous beta 2-microglobulin (shown by FCM analysis) as a single allelic product without reexpression of any endogenous class I gene (shown by 1D.IEF analysis). Furthermore, TNF-alpha and IFN-gamma, alone and synergistically, increase cell surface expression of transfected MHC class I/endogenous beta 2m heterodimers without induction of endogenous class I alpha-chain genes. These data show that the MHC class I-negative JAR human cell line might be used for transfections with the aim of establishing human cells expressing just one defined MHC class I allele for functional and regulatory studies. These findings are discussed in relation to the methylated status solely of endogenous class I alpha-chain genes in JAR cells and suggest that transfected class I genes are not regulated in the same fashion and, in particular, that constitutive and TNF/IFN inducible trans-acting regulatory factors able to bind to cis-promoter/enhancer sequences of class I DNA are likely to be present. PMID- 1905427 TI - Parameters of growth in primary cultures and cell lines established from Drosophila imaginal discs. AB - We have further characterised our tissue culture system for the growth in vitro of Drosophila imaginal disc cells, including the culture medium requirements for optimum growth and we have adjusted the protocol recommended for the initiation of cultures. Many imaginal disc fragments become organised into vesicles, and some of these secrete extracellular material into the lumen. Sensory axons differentiate in primary disc cultures, in the absence of bristle formation. The early stages of cell division to form a cell line are recorded. PMID- 1905428 TI - Role of the basilar artery in regulation of blood flow to the brain stem in rats. AB - Large arteries contribute to the regulation of cerebral blood flow. The goal of this study was to examine the effects of changes in diameter of the basilar artery on blood flow to the brain stem. We measured blood flow with laser-Doppler flowmetry in anesthetized rats. The topical application of 10(-6) M serotonin, which selectively constricts large arteries, reduced diameter of the basilar artery by 47 +/- 5% (mean +/- SEM, n = 6) but did not alter blood flow to the ventral brain stem (change in blood flow -2 +/- 5%). The topical application of 10(-8) M vasopressin, which affects both large and small vessels, decreased blood flow by 33 +/- 4% (n = 6). In rats with spontaneous vasomotion, the basilar artery showed rhythmic changes in diameter at a frequency of 4.0 +/- 0.1 cycles/min and an amplitude of 20 +/- 1% of mean diameter (n = 6). Blood flow to the ventral brain stem cycled at the same frequency as and in phase with changes in diameter of the basilar artery, with an amplitude of 15 +/- 1%. We conclude that constriction of the basilar artery may occur with no change in brain stem perfusion. The distinct changes in blood flow during spontaneous vasomotion suggest that vasomotion occurs in intraparenchymal arterioles as well as in the basilar artery. PMID- 1905429 TI - Effect of tissue plasminogen activator on intimal platelet accumulation in cerebral arteries after subarachnoid hemorrhage in cats. AB - Recombinant tissue plasminogen activator may be effective in preventing cerebral vasospasm after subarachnoid hemorrhage by resolving subarachnoid clots. We previously demonstrated that blood placed on the adventitial surface of cerebral arteries enhances intimal platelet accumulation, positively correlating with endothelial damage and other pathologic changes in vessel walls. In this study, we investigated the ability of a single bolus injection of tissue plasminogen activator to prevent platelet accumulation in cerebral vessels after subarachnoid hemorrhage. Subarachnoid hemorrhage was produced in cats by the transorbital intracisternal injection of 2.5 ml autologous arterial blood around the proximal part of the right middle cerebral artery. In 10 animals, 25 micrograms tissue plasminogen activator was injected at intervals of 10 (five cats) and 60 minutes (five cats) after subarachnoid hemorrhage. Intracisternal physiological saline (0.5 ml) was injected in six cats 10 minutes after subarachnoid hemorrhage. Platelets labeled with indium-111 were injected intravenously just before subarachnoid hemorrhage, and their radioactivity was measured in cerebral arteries at death. The results indicated that, after subarachnoid hemorrhage, early injection of tissue plasminogen activator inhibited intimal platelet accumulation, but later injection did not, although the extent of subarachnoid clot was reduced at both plasminogen injection times. PMID- 1905430 TI - Intracarotid saline infusion improves outcome from incomplete ischemia in rats. AB - Previous studies suggest that rheological changes associated with ischemia may produce postischemic hypoperfusion. We tested whether intracarotid or intravenous infusions of saline improve neurological outcome from incomplete cerebral ischemia in rats. Rats were anesthetized with 1.4% isoflurane in air, and ischemia was produced by unilateral carotid artery ligation combined with hemorrhagic hypotension to 30 mm Hg for 30 minutes. Intracarotid (n = 10) or intravenous (n = 10) saline infusion (0.3 ml/min) decreased hematocrit 20% compared with control rats (n = 10). Neurological outcome was significantly improved in rats infused with intracarotid (p less than 0.05) but not intravenous saline during ischemia without a change in brain temperature. Cerebral blood flow, measured in a separate study using laser Doppler flowmetry (n = 5), decreased 70% (p less than 0.01) during carotid ligation and hypotension but was not changed by intracarotid saline infusion (p greater than 0.30). These results show that perfusion of ischemic brain with saline improves outcome by factors not related to changes in hematocrit, brain temperature, or intraischemic tissue blood flow. PMID- 1905431 TI - Flecainide: what are we measuring? PMID- 1905432 TI - [Gastrostomy. Simplified technique and extended field of indications]. AB - The technique by which percutaneous access to the stomach for enteral nutrition is obtained is generally accepted in cases in which swallowing is defective and for aspiration in cases of gastro-intestinal retention. Experience with a gastrostomy tube developed in Denmark has provided inspiration to establish access by means of outpatient intervention. Since 1986, 15 patients with defective swallowing were treated as outpatients with percutaneous introduction of a gastrostomy tube without complications of the intervention or to subsequent management in nursing homes or their own homes. Replacement of the catheter was undertaken by the general practitioner or by renewed outpatient visits. In many of the patients, replacement of the catheter was performed by the caring staff. A narrow-bore tube was chosen primarily in order to reduce the risk of complications. Despite the narrow-bore tube, the effect of the decompression tube has proved satisfactory in five patients since 1986. The method is simple, the trauma minimal and it is well accepted by the patients. PMID- 1905435 TI - [A new method of cultivating Mycobacterium tuberculosis]. AB - The possibility is shown of microcultivation of Mycobacteria tuberculosis on semipermeable cellophane membranes covering solid nutrients. The new method of cultivation may be used for enhanced microbiological diagnosis of tuberculosis, for determination of drug resistance of the tuberculous pathogen as well as for assessment of the biological properties of Mycobacteria tuberculosis in live unstained culture. PMID- 1905434 TI - [Changes in plasma lipids, lipoproteins and utilization of energy substrates during continuous enteral nutrition with 50% medium chain triacylglycerols (Preciten MCT 50)]. AB - Enteral nutrition (EN) containing part of the energy substrates in the form of triacylglycerols with medium chain fatty acids (MCT) has a number of advantages in particular in patients with an impaired utilization of energy and impaired nutrient absorption from the small intestine. The increased MCT supply reduces the risk of the development of shock lung, consumption coagulopathy and has a very favourable effect in patients with severe catabolism associated with Crohn's disease. On the other hand EN containing MCT may produce also some undesirable effects such as deterioration of glucose utilization in the liver, changes, on the composition of plasma lipids and lipoproteins and an undesirable thermogenic effect. Investigations of the effect of EN containing 50% of fat in the form of MCT (Preciten MCT 50R, Sandoz Nutrition-Wander) indicate that even an energy supply corresponding to 1.7 X REE in the form of EN with 50% MCT does not lead to a statistically significant rise of REE, does not produce a marked thermogenic effect and the value of the respiratory quotient (RQ) does not increase significantly. Already after 8 days of EN significant changes occur in the spectrum of lipids and lipoproteins characterized by a decline of high density lipoproteins HDL3 (p less than 0.05). The parallel decline of low density lipoproteins LDL and VLDL, however, is the reason why adverse changes of the atherogenic index do not occur. PMID- 1905433 TI - Identification and characterization of a Hantavirus strain of unknown origin by nucleotide sequence analysis of the cDNA derived from the viral S RNA segment. AB - The genetic characterization of a serologically Hantaan-like virus but of unknown origin (termed DX) was carried out by molecular cloning and nucleotide sequencing of the corresponding cDNA of the viral S RNA segment. The S RNA was found to be 1765 nucleotides long with 3' and 5' termini being complementary for 24 bases. The virus messenger-sense RNA contains one major open reading frame (ORF) encoding 428 amino acids or a 50 kD polypeptide. A comparison of the DX S RNA segment to those of Sapporo rat, Hantaan, Puumala/Hallnas B1, and Prospect Hill viruses reveals 95.4, 71.3, 55.3, and 60.9% homology at the nucleotide sequence level, and 94.7, 80.1, 58.4, and 59.8% at the deduced amino acid sequence level. Thus Hantavirus strain DX is very closely related to Sapporo rat virus. We also analyzed the S RNA segments of these Hantaviruses for the presence of a second ORF encoding a potential nonstructural NSs protein. All potential second ORFs detected in the different S RNA segments differ substantially in length and position among the viruses, despite the high conservation of the nucleotide sequences and the overall structure of the nucleocapsid proteins. This suggests that the nucleocapsid protein is the only polypeptide encoded by Hantavirus S RNA segments, setting them apart from the other members of the Bunyaviridae family. PMID- 1905436 TI - Human liver sulphotransferase and UDP-glucuronosyltransferase: structure-activity relationship for phenolic substrates. AB - 1. Human liver sulphotransferase and UDP-glucuronosyltransferase were studied with phenol, methyl-, ethyl-, propyl-, butyl-, phenyl-, nitro-, amino-phenols and hydroxybenzoic acids as substrates. 2. The Michaelis-Menten constants (Km) and the maximum velocities of reaction (Vmax) of sulphotransferase and UDP glucuronosyltransferase for each substrate were measured. 3. The Km values for sulphotransferase varied over 5000-fold whereas they varied over 25-fold for UDP glucuronosyltransferase. 4. Sulphotransferase and UDP-glucuronosyltransferase have different structure-activity relationships with phenolic substrates. PMID- 1905437 TI - Occurrence of a cytochrome P-450-containing mixed-function oxidase system in the pond snail, Lymnaea stagnalis. AB - 1. The occurrence of an as yet unidentified cytochrome P-450 in the microsomal fraction of the digestive gland of the snail, Lymnaea stagnalis was studied. 2. Studies in vivo and in vitro (digestive gland homogenates or the 170,000g fraction) of the cytochrome P-450-mediated metabolism of substrates such as biphenyl, pentoxy- and ethoxy-resorufin and aminopyrine have been made. 3. Cytochrome P-450 concentration in the digestive gland calculated from CO difference spectra was 0.30 +/- 0.05 nmol/g tissue. This amount was not increased either by phenobarbital or by 3-methylcholanthrene. 4. Aniline binding spectra resembled normal type II spectra, while type I model substrates such as hexobarbital and 2,2'-dichlorobiphenyl showed type II- or reversed type I-like spectra. 5. O-Deethylation of 7-ethoxyresorufin did not occur, but 7 pentoxyresorufin O-depentylation activity (80.4 +/- 28.6 pmol resorufin/g per hour) and aminopyrine N-demethylation activity (375 +/- 96 pmol formaldehyde/g per minute) were demonstrated. 6. 4-Hydroxybiphenyl was the major metabolite of biphenyl, while minor amounts of 2-hydroxybiphenyl were formed (in vivo: 63.7 nmol 4-hydroxybiphenyl and 3.33 nmol 2-hydroxybiphenyl per snail per 24 h, after an oral dose of 778.2 nmol biphenyl; in vitro 118 +/- 21 pmol and 21 +/- 9 nmol, respectively (digestive gland homogenate/mg protein, per hour). 7. The results indicate that the isoenzymes involved in the observed MFO activities resemble isoenzymes P-450b/e. PMID- 1905438 TI - Pharmacist interventions improve fluid balance in fluid-restricted patients requiring parenteral nutrition. AB - Many intensive care unit (ICU) patients require parenteral nutrition (PN) and fluid restriction, making delivery of adequate nutrition difficult. We studied the effects of pharmacist interventions on fluid balance in fluid-restricted ICU patients requiring PN. Twenty patients were randomized to the treatment group (dextrose 70% injection [D70W] plus 15% amino acids for PN, 25-mL piggybacks, selected drugs added to the PN solution) or the control group (D70W plus 10% amino acids, 50- or 100-mL piggybacks). Each group contained 10 patients and they were not significantly different for age, gender, weight, hospital days, and serum albumin concentration. The duration (9.3 +/- 1.2 vs. 9.7 +/- 2.4 d) and doses of PN (29 +/- 6.8 vs. 28.7 +/- 6.9 kcal/kg/d; 1.1 +/- 0.3 vs. 1.1 +/- 0.4 g/kg/d protein) were similar between treatment and control groups. Mean fluid intake (3112 +/- 1146 vs. 3498 +/- 1111 mL/d), fluid balance (146 +/- 1581 vs. 708 +/- 1402 mL/d), and cumulative fluid balance (1358 vs. 6867 mL) were all significantly lower in the treatment group. Mean fluid output was similar between the two groups. Pharmacist interventions can significantly decrease intake and result in a better fluid balance in fluid-restricted ICU patients who require PN. PMID- 1905439 TI - Delirium in an elderly woman possibly associated with administration of misoprostol. AB - Misoprostol has been associated with adverse reactions, including gastrointestinal symptoms, gynecologic problems, and headache. Changes in mental status, however, have not been reported. We present a case in which an 89-year old woman in a long-term care facility became confused after the initiation of misoprostol therapy. The patient's change in mental status was first reported nine days after the initiation of therapy. Her delirium significantly improved after misoprostol was discontinued and her mental status returned to normal within a week. Because no other factors related to this patient changed significantly, the delirium experienced by this patient possibly resulted from misoprostol therapy. PMID- 1905440 TI - Aseptic meningitis and muromonab-CD3 therapy. PMID- 1905441 TI - Altretamine. AB - Altretamine is a National Cancer Institute-designated group C antineoplastic agent used in the treatment of advanced ovarian cancer. Altretamine is a highly lipid-soluble drug available only for oral administration as a capsule. The drug is activated through metabolic oxidation to intermediate methylol derivatives and formaldehyde. It is unclear which metabolite is the major species responsible for cytotoxicity or the primary mechanism of cytotoxicity. As a single agent in the treatment of ovarian cancer, altretamine demonstrates a response rate similar to other active agents in this disease (21-39 percent). The major utility of altretamine is in combination with other agents such as cyclophosphamide, doxorubicin, fluorouracil, melphalan, and cisplatin. However, few randomized trials have evaluated the contribution of altretamine in these multiagent combinations. Dose-limiting toxicities include gastrointestinal (nausea, vomiting, anorexia), hematologic, and neurotoxic (peripheral neurotoxicity). The therapeutic role of altretamine is limited because of a toxicity profile similar to that of cisplatin, one of the more active agents in ovarian cancer. Its use should be reserved for patients who are not candidates for more standard platinum based regimens. PMID- 1905442 TI - [Therapy-induced cerebro-renal oxalosis?]. AB - Report on three cases of a cerebro-renal oxalosis. The clinical picture was characterized by subacutely appearing coma and cerebral paroxysms. Death occurred due to break-down of cerebral regulation. In all three cases the post-mortem examination showed massive subendothelial depositions of double refractive crystals in the cerebral vessels, in particular in the stem ganglia regions and in the renal tubuli. The crystals showed several features typical for calcium oxalate. The clinical picture appears as an infrequent complication within intensive medicine, in connection with parenteral administration of xylit. Differential diagnosis, pathogenesis and possible cofactors are discussed. PMID- 1905443 TI - Influence of tissue acidification and halothane anesthesia on hepatic electrical and biochemical properties during ischemia. AB - In order to further corroborate the recent findings on liver ischemia after perfusion with solutions containing an additive of heptanol, that the intraischemic loss of cell-to-cell communication in protected livers can be detected by electrical impedance measurement (1), we tried to induce uncoupling in porcine liver by tissue acidification applying acidified protective solutions. Moreover, the effects of preischemic inhaling of high concentrations of the decoupling anesthetic halothane were examined in unprotected ischemic livers (2 5). Electrical impedance, biochemical analyses, and pH measurements were applied in parallel. In addition, typical time courses of impedance parameters of unprotected liver and skeletal muscle were compared, because the latter is devoid of gap junctions. In spite of overlapping side-effects of the respective uncoupling measure, the results suggest that the loss of cell-to-cell communication in the liver is associated with measureable effects on the electrical impedance. PMID- 1905444 TI - [Non-tropical sprue and chronic inflammatory rectal stenosis in a patient with abuse of ergotamine-containing suppositories]. AB - A 51 year old Yugoslavian patient was admitted to our hospital in reduced general condition with distinct hypocalcemia, osteomalacia, and with rectum stenosis. Our investigations led to the diagnosis of a malabsorption syndrome due to non tropical sprue. The most likely cause of the rectum stenosis is an abuse of ergotamine-containing suppositories for several years. A gluten-free diet and the interruption of the use of the suppositories improved her general condition remarkably. PMID- 1905445 TI - [Effect of food characteristics on rate of hemorrhagic complications and early results of endoscopic sclerosing treatment of esophageal varices]. AB - To evaluate the possible influence of the trauma of swallowing solids on the outcome and complication rate of endoscopic injection sclerotherapy we carried out a prospective randomized trial in 46 cirrhotics undergoing sclerotherapy because of recent or acute variceal bleeding. The patients were randomly assigned to mashed food (24 = group A) or normal solid food (22 = group B). Both groups were comparable according to age, sex, Child classes, size of the varices and patients undergoing emergency sclerotherapy (8 in each group). Duration of hospital care (A 26.6, B 27.3 days) (means), number of endoscopic studies (A 4.7, B 4.6), number of sclerotherapy sessions (A 2.4, B 2.5) and required amount of Polidicanol in each patient (A 62.7, B 56.4 ml) were not different. Variceal eradication was achieved in 13 cases in A, in 14 in B. III degrees varices remained in 6 patients in A (3 quit against advice before completing ST) and in 1 case in group B. Staple-gun transection and devascularization because of recurrent bleeding were necessary in 2 cases in A and in 1 case in B. Death occurred in 2 cases in A (liver failure), in 4 cases in B (3 cases of liver failure and in 1 case with recurrent bleeding, without operation because of hepatocellular carcinoma). Episodes of acute massive bleeding from varices or esophageal ulcers occurred 9 times in group A and 10 times in group B. Minor bleedings occurred 10 times in A and 9 times in B. Transfusion requirement was 110 units of packed red cells in A and 106 in B.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1905446 TI - Stable Listeria monocytogenes live vaccine candidate strains with graded attenuation on the mouse model. AB - Metabolic drift (antibiotics resistance) mutations were used to construct stable two (and three) marker vaccine candidate strains of the predominant Listeria monocytogenes serotypes 1/2a and 4b by stepwise selection. Derived from wild-type strains, spontaneous chromosomal streptomycin-resistant clones with their i.p. LD50 elevated from less than or equal to 10(5.0) c.f.u. to approximately 10(6.1) c.f.u. were used in the second step to isolate the rifampicin-resistant mutants with i.p. LD50 values ranging from 10(6.6) to 10(7.4). On i.p. immunization with fully tolerated doses (less than or equal to 1% LD50), these potential vaccine strains were found to protect not less than 95% of the mice against a lethal (approximately 100 LD50) challenge with the homologous wild-type strain. Further elevation of the i.p. LD50 to greater than 10(8.3) c.f.u. by means of a third attenuating fosfomycin-resistance marker resulted in overattenuation and reduced protective capacity. PMID- 1905447 TI - New trends in the use of Al(OH)3-conjugated endotoxins and their subunits from the S- and R-forms of Shigella dysenteriae serovar 1 for model vaccination purposes. AB - The lipopolysaccharides, lipopolysaccharide-protein complexes and their lipids A, isolated from Shigella dysenteriae 1, exhibited lethal toxicity (LD50 300-400 micrograms per mouse), pyrogenicity (0.01-1.0 microgram), activity in the Limulus test (10(-3)-10(-12) mg ml-1) and produced a positive local Shwartzman reaction. It was found that these substances bound to Al(OH)3 were capable of successfully protecting mice from challenge with both homologous and heterologous infections (up to 90% of mice survived a challenge with LD100), whereas immunization with substances with no biological carrier exhibited very low or zero protective effects. Furthermore, the positive cross-reactivity of lipids A in the agar immunodiffusion test confirms the wide applicability for vaccination purposes. PMID- 1905448 TI - [... with reference to patient safety...]. PMID- 1905449 TI - The determination of anthropometric cut-off points for protein-energy malnutrition using the maximum chi-squared statistical technique. AB - The Wellcome cut-off points for the classification of protein-energy malnutrition are arbitrary values. A simple technique, with the use of maximum chi-squared statistics, for the determination of cut-off points for anthropometric indicators for the assessment of malnutrition is presented. This technique has been applied to pre-school-age children in Lae, Papua New Guinea. In this population the cut off points for the anthropometric indicators related to age, of body weight, height, triceps skinfold, arm circumference and arm muscle circumference, have been determined as 87%, 90%, 97%, 93% and 100%, respectively, of the international standards. PMID- 1905450 TI - Photobleaching of astaxanthin and canthaxanthin. Quantum-yields dependence of solvent, temperature, and wavelength of irradiation in relation to packaging and storage of carotenoid pigmented salmonoids. AB - The quantum yield for the photobleaching of astaxanthin (the carotenoid of wild salmonoids) and of canthaxanthin (the closely related carotenoid used as a feeding additive for farmed salmonoids) has been determined for monochromatic light at different wavelengths and in different solvents. Astaxanthin is less sensitive to light than canthaxanthin. The photobleaching is strongly wavelength dependent, and the quantum yield for astaxanthin dissolved in chloroform at 22 degrees C is 3.2 x 10(-1) mol.Einstein-1 at 254 nm, 3.1 x 10(-2) at 313 nm, and 1.6 x 10(-6) at 436 nm, respectively. The quantum yields are less dependent on the nature of the solvent and show no simple correlation with oxygen solubility, i.e. for 366 nm excitation of astaxanthin the quantum yields are 6.1 x 10(-5) mol.Einstein-1 in acetone, 1.2 x 10(-4) in saturated vegetable oil, 1.9 x 10(-4) in chloroform, and 3.4 x 10(-4) solubilized in water, respectively. The photobleaching quantum yield provides an objective measure of the light sensitivity of the carotenoids in relation to the discolouration of carotenoid pigmented salmonoids. The quantum yield was also found to be independent of the carotenoid concentration and, in a homogenous solution, of light intensities. For astaxanthin solubilized in water, the quantum yield increases for low light intensities. Excitation of astaxanthin solubilized in water using visible light shows that the photobleaching quantum yield is independent of temperature, while excitation at 313 nm shows an increase in the quantum yield with increasing temperatures, corresponding to an energy of activation of 28 kJ.mol-1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1905451 TI - Pharmacokinetics and pharmacodynamics of different doses of Irtemazole in repeated application. AB - Irtemazole, a new uricosuric substance, was tested in 12 normouricemic subjects in doses between 6.25-37.5 mg applied twice daily for 7 days per os. The plasma uric acid level decreased in all subjects, to a constant level within 1-2 days with application of the higher doses, and within 2-3 days with application of the lower doses, and was maintained as long as irtemazole was given. The average decrease of plasma uric acid was 20.4% at a dose of 6.25 mg irtemazole, 22.7% at 12.5 mg, 42.0% at 25 mg, and 45.7% at 37.5 mg. The renal uric acid excretion and the uric acid clearance increased to a constant level within 1 day of irtemazole application. The initial levels of plasma uric acid, uric acid excretion, and uric acid clearance were reached after 1-2 days after cessation of irtemazole. Within 1 to 2 days after ingestion of irtemazole a constant plasma irtemazole level and renal irtemazole excretion were observed in all doses throughout the application period. One to 2 days after discontinuation of irtemazole it was no longer detectable in plasma and urine. No side effects were found. PMID- 1905452 TI - [A rare arthrosis of the metacarpophalangeal joints--a degenerative disease in heavy manual labor]. AB - We identified eight patients (10%) suffering from metacarpophalangeal (mcp) osteoarthritis in a group of 81 men doing hard manual labor for more than 10 years. There was no case of mcp osteoarthritis in a group of 65 men which had not performed hard manual labor. The most essential clinical symptom was mild to moderate pain in all cases, followed by deformities, stiffness, reduced subjective grip strength, decreased range of motion, and soft-tissue swelling, listed in order of decreasing frequency. In the first group, we found a higher frequency of other localizations of interphalangeal osteoarthritis. It seems remarkable that in three patients the osteoarthritis of the mcp joints was isolated, without degenerative changes of the other finger-joints. The typical localization of the mcp osteoarthritis was the second and the third fingers, most frequently of the right hand in patients with known right-handedness (but the finding lacks statistical significance). Radial, hook-like osteophytes, and ulnar, blunt-shaped osteophytes were recorded as morphologic characteristics. Extreme stress of the finger joints by intense gripping and handling of heavy tools, and microtrauma caused by vibrating tools are discussed as causative factors. PMID- 1905453 TI - [The genetic basis of suppression of tumors and metastases in Drosophila and man]. AB - The first causal relations between recessive gene mutation and malignancies were detected in a fly (Drosophila melanogaster). This is a recessive-lethal heredity. Tumour suppression was demonstrated in mouse cell hybrids in the late sixties. Tumour suppressor antigens are developed recently for Wilms tumour, retinoblastomas and colorectal cancer. PMID- 1905455 TI - Cost-effectiveness evaluation of measles immunization strategies on a college campus. AB - Since live rubeola vaccine became available in 1963, routine immunization of children at age 15 months has been the recommended strategy for eliminating measles in the United States. However, due to increasing measles outbreaks, especially among previously immunized populations, the Immunization Practices Advisory Committee (ACIP) recently recommended modifying the one-dose measles vaccination policy to a two-dose schedule, one at 15 months and one at age 5 or 6 years. To address the present college population, ACIP recommended vaccinating all college students who lack proof of immunity. We used the methods of decision analysis to examine the cost effectiveness of implementing such a program in a specific college population, namely, students at the University of California at Los Angeles (UCLA). We developed a model to examine three possible vaccination strategies: "wait," "screen," and "vaccinate all." Estimates of probabilities and cost were derived from several outbreaks at UCLA as well as statewide data. In the baseline case, the least expensive strategy is to wait until an outbreak occurs before implementing a vaccination program. The additional cost incurred by screening per measles case avoided is $122,871. However, using sensitivity analysis, we found that the overall cost of elective vaccination strategies is driven by the cost of the vaccine itself. If vaccine could be provided at a nominal cost to the university, a strategy of vaccinating all students without proof of immunity (by either history of two vaccinations or positive titer) would provide the high level of immunity needed to prevent outbreaks and still be most cost effective ($16,644 per measles case avoided). PMID- 1905454 TI - Functional respiratory chain studies in mitochondrial cytopathies. Support for mitochondrial DNA heteroplasmy in myoclonus epilepsy and ragged red fibers (MERRF) syndrome. AB - Mitochondrial respiratory chain function was investigated with polarographic and enzymatic studies, and correlated with immunoblot studies using a battery of probes against respiratory chain holocomplexes in a series of patients with myoclonus epilepsy and ragged red fibers (MERRF) syndrome. State III respiration rates in intact skeletal muscle mitochondria were normal in two cases, suggested site I deficiency in one case and a mid-respiratory defect in another. Immunological studies of complex I showed reduced levels of several subunits with the apparent absence of two bands (which at 45 and 42 kDa, coincide with the predicted electrophoretic mobility of the ND5 gene product) in one case. Complex I, III and IV composition was normal in the other three cases indicating no major disruption of complex assembly. A differing severity of skeletal muscle respiratory chain impairment in a group of unrelated patients with severe cerebral clinical involvement is best explained by uneven tissue distribution between brain and muscle of a heteroplasmic mtDNA mutation. The relationship between MERRF and mitochondrial encephalomyopathy, lactic acidosis and stroke like episodes (MELAS) encephalopathies is reappraised by extension of this hypothesis. PMID- 1905456 TI - Oxidative mechanisms underlying methyl mercury neurotoxicity. AB - Cerebellar granule cells from 5-12-day-old rats can be incubated in suspension at 37 degrees C for up to 3 hr with minimal decline in viability. Methyl mercury was found to produce time- and concentration-dependent cell killing with greater than 85% cell death after 3 hr exposure to a concentration of 20 microM. Previously characterized inhibition of protein and RNA synthesis as well as known methyl mercury-induced defects in cellular ATP production have been shown to be incapable of causing this degree of cell death. Here we report that methyl mercury induced a concentration-dependent increase in membrane lipoperoxidation and a rapid decline in reduced glutathione in this cerebellar neuronal preparation. Hydrogen peroxide at 5 mM was found to closely reproduce each of the cytotoxic effects manifested by methyl mercury suggesting that oxidizing conditions produced by methyl mercury may account for the observed cell death. Methyl mercury-induced lipoperoxidation was not the cause of cell death since malonaldehyde production could be blocked by alpha-tocopherol or EDTA without appreciable protecting against cell death. Significant protection from methyl mercury-induced cell death was observed, with EGTA, deferoxamine and KCN. We propose that oxidative events contribute to the toxic mechanism of action of methyl mercury in isolated cerebellar granule neurons. PMID- 1905457 TI - Evaluation of the effects of inhibition of monoamine oxidase and senescence on methamphetamine-induced neuronal damage. AB - The administration of high doses of methamphetamine causes long lasting damage to central dopaminergic and serotonergic neurons through a mechanism known to involve presynaptic, cytoplasmic stores of those transmitters and thought to be dependent upon a free radical reaction. The following studies were designed to determine if differential inhibition of the subtypes of monoamine oxidase would alter the magnitude of the methamphetamine induced neuronal damage. In addition, since monoamine oxidase type B increases with age, the effects of high dose administration of methamphetamine were evaluated in senescent mice. It was observed that inhibition of monoamine oxidase type A, and to a lesser degree, type B, increased the magnitude of methamphetamine-induced neuronal damage and that aged mice were more sensitive to the toxic action of methamphetamine. These results are interpreted with respect to the use of monoamine oxidase inhibitors in the treatment of Parkinson's disease. PMID- 1905458 TI - [Does total androgen suppression in advanced prostatic cancer induce a greater number of complete remissions? A phase II trial]. AB - The present Phase II study's main objective was to evaluate the rate of complete responses (CR) obtained through total androgenic suppression (TAS) in patients with disseminated prostate carcinoma. Twenty consecutive patients were recruited of which 19 were evaluable for response and toxicity. Treatment consisted in an association of orchiectomy or the analogous LH-RH Buselerin with the antiandrogenic Flutamide. There was 1 CR (5%) and 17 partial responses (PR). Sixteen patients with symptomatic disease had subjective improvement, usually during the first month of treatment. After an average follow-up of 20 months (range 7-29), 1 patient remains CR and 7 have regressed following PR, 4 of which have died. Tolerance was good, and side effects secondary to hypoandrogenism were frequent, although mild, requiring treatment discontinuation in 1 case. It is concluded that TAS is an excellent palliative approach in disseminated prostate carcinoma though the rate of CRs obtained is sensibly lower to that reported by Labrie (28.3%) and in the range of 0-8% achieved in most studies. It is questionable whether it will become standard therapy for metastatic prostate carcinoma. PMID- 1905459 TI - Immunosuppressive substances from blue-green algae. PMID- 1905460 TI - Lipoxygenase-inhibitory azomethines and benzoylhydrazones. II. Effects of phenylsubstituted azomethines on the antigen-induced contractions of guinea pig lung parenchymal strips and jejunum segments. PMID- 1905461 TI - CGP 28,238, a new potent nonsteroidal anti-inflammatory agent: its relation to arachidonic acid metabolism. PMID- 1905463 TI - Autoimmune haemolytic anaemia associated with low-titre anti-i cold agglutinins in a Nigerian. A case report. AB - A case of autoimmune haemolytic anaemia due to low-titre anti-i cold agglutinin in a Nigerian is described. The patient presented with chronic haemolytic anaemia with a positive direct antiglobulin test, the cells reacting with anticomplement (anti-C3). Further tests showed that the antibody was a low titre (1 in 512) cold anti-i antibody with a wide thermal amplitude. The case reported appears to be the first case of cold haemagglutinin disease in a Nigerian. PMID- 1905462 TI - Mammalian lipoxygenases--are they only involved in the arachidonic acid cascade? PMID- 1905464 TI - Chronic leg ulcers in sickle cell disease: experience in Ibadan, Nigeria. AB - The prevalence of chronic leg ulcers was investigated in 872 adults with sickle cell disease (SCD) (630 HbSS and 242 HbSC) at Ibadan, Nigeria. The incidence was 7.5% in HbSS and 1.7% in HbSC patients. The sex ratio in HbSS was 2:1 in favour of males, and three of the four HbSC were females. Ulcers were sited around the ankles in more than 70% of the patients. The duration of the ulcers varied from less than 1 year to more than 20 years. There was no bias for social class. Response to therapy, including autologous skin graft, was poor. PMID- 1905466 TI - The prevalence of infertility in a rural Nigerian community. AB - The prevalence of infertility in a rural Nigerian community is determined by a systematic random sampling of the population. The overall prevalent rate was 30.3%, giving indices of 9.2% for primary infertility and 21.1% for secondary infertility. Primary infertility is rare after the age of 30 years and acquired causes of infertility are responsible for the high prevalence rate. Genital infections (post-abortal and puerperal) are major contributory factors to the high rate of infertility. Liberal abortion laws, improved socio-economic status and elimination of harmful socio-cultural beliefs and practices would reduce the problem of infertility to the barest minimum in the developing countries. PMID- 1905465 TI - A health examination survey of morbidity in rural Nigeria. AB - A health survey to describe the morbidity pattern of a rural population in Nigeria was conducted among a 10% random sample of 1091 households in the Kainji Lake area of Nigeria. The diseases most frequently encountered were fevers, gastro-enteritis and chest infections, with prevalence rates of 50.2%, 37.1% and 10.0% respectively. Dental debris, conjunctival pallor, missing teeth and dental calculi were present in 65.8%, 59.1%, 32.2% and 24.1% respectively. The adult males were found to be significantly taller and heavier and with higher blood pressure than the females. Most of the health problems were attributed to various types of infection, but unhealthy social habits, lack of sanitation facilities and poor personal hygiene could have contributed to the overall morbidity in the population. Control of communicable diseases, community mobilization towards provision of basic sanitation facilities, good housing and dental hygiene were recommended to be included in health planning for the Kainji Lake area population. PMID- 1905467 TI - The prevalence of Gardnerella vaginalis, Trichomonas vaginalis and Candida albicans in the cytology clinic at Ibadan, Nigeria. AB - In a study of 2224 adult women from the cytology clinic of the University College Hospital, Ibadan, Nigeria, the prevalence of 'specific vaginal infection' (i.e. Gardnerella vaginalis, Trichomonas vaginalis and Candida albicans) was 14.5%. For individual organisms, the rates were 9.76% for G. vaginalis, 2.52% for T. vaginalis and 2.20% for C. albicans. About half of the patients were asymptomatic while others were referred from other clinics with vaginal discharge, cervical erosion, post-coital bleeding, intermenstrual bleeding and various other symptoms and signs. The infections were almost uniformly distributed in all age groups studied. Increasing promiscuity either as a result of increased mobility of husbands (due to economic depression) or increased use of contraception by older women was thought to be responsible for the persistence of these infections in those aged 45 years and above. In addition, Gardnerella vaginalis, Trichomonas vaginalis and Candida albicans infections can also be easily diagnosed from cervical cytology, by identification either of the organism or of characteristic cytological cellular changes. PMID- 1905468 TI - Ocular gun-shot injuries in Ibadan. AB - Twenty patients with eye injuries resulting from gun-shots were admitted to the University College Hospital, Ibadan, over a 10-year period. Three of the patients had involvement of both eyes, making a total of 23 eyes. Seven eyes had contusion injuries, while 16 had perforating injuries. Eight of the perforating group had primary evisceration, two refused evisceration and six had repair of corneal/corneo-scleral wounds. All seven eyes in the contusion group were treated conservatively and four retained a vision of better than 6/36. Seven out of the 20 patients were shot by someone else, six of whom were armed robbers. The other 13 patients were shooting animals while hunting, when the gun either backfired or exploded in their faces. PMID- 1905470 TI - Body temperature in the Nigerian neonate--comparison of axillary and rectal temperatures. AB - Body temperature was measured in 104 healthy full-term neonates of appropriate weights using the rectal and axillary routes simultaneously at 1, 2, 3, 5 and 7 min after placement of the thermometer. Normal body temperature in the Nigerian newborn, irrespective of the site where it was obtained, ranged from 35.9 degrees C to 37.5 degrees C. There was a strong positive correlation between axillary and rectal temperatures (r = 0.9). Prior to stabilization, mean rectal temperatures at every minute were significantly higher than axillary temperatures, (P less than 0.001). Although rectal temperatures stabilized earlier than axillary temperatures (3 min and 5 min respectively), the difference between mean stabilized temperature taken at the two sites was not significant (P greater than 0.05). This study provides normal reference data on body temperature in the Nigerian newborn. It is suggested that the axillary route be used more frequently when taking temperature in the newborn because of its safety and its good correlation with the rectal temperature readings. PMID- 1905469 TI - Mothers as agents of growth monitoring: implications for widespread community growth monitoring. AB - A total of 518 mothers, aged 18 to 45 years, were interviewed to study a variety of indicators and local standards used to assess the course of their children's growth. The features most frequently recognized by mothers as indicators of growth were related to maternal age, parity and educational status. The younger mothers (age less than or equal to 30 years and parity less than or equal to 3) used weight and health frequently to assess growth, while the older mothers recognized growth by comparison with other children and changes in mood (P less than 0.01). The latter two indicators were found to be a function of maternal experience. Unlike age and parity, age and education seemed to have no joint association with the various responses. We conclude and recommend that weight, health and stages of development are reliable and acceptable indices for community growth monitoring. PMID- 1905471 TI - Child abuse and neglect: a global phenomenon. AB - Child abuse and neglect are worldwide phenomena which seem to be assuming epidemic proportions in the U.S.A. Four conditions are usually considered under child abuse and these include physical abuse, physical neglect, sexual abuse and emotional maltreatment. The various predisposing factors to abuse or neglect of children in developed and developing countries are considered. The apparent low incidence of cases of child abuse in Nigeria may not be unrelated to our inability to recognize and report cases as they occur. The primary health physician therefore has a challenge to suspect, detect, treat promptly and report such cases. The urgent need for a multidisciplinary approach to the problem of child abuse and neglect in Nigeria is stressed. PMID- 1905472 TI - Low protein/high calorie dietary regimen in the management of chronic renal failure. A preliminary study of Nigerian patients. AB - The progression of renal failure was evaluated in seven patients with established chronic renal failure (mean serum creatinine 4.17 mg%), while on a supervised dietary regimen consisting of low protein of high biological value (20-30 g/day), and a high calorie content (3000 kcal/day) for a period of between 18 and 28 months. Five other patients with a comparable degree of chronic renal failure whose protein intake was unrestricted (evaluated to vary between 40 and 60 g per day) served as controls. In the study group, serum creatinine levels stabilized or improved in five, while a moderate rise was observed in two. In contrast, a considerable and significant rise in serum creatinine values was observed in all the controls. Two significantly different slopes (P less than 0.01) were also obtained from the linear regression analysis of the reciprocal of serum creatinine values against time, for the two groups. Our preliminary observation of a beneficial effect of this regimen in our patients is particularly relevant to the developing countries because of the high prevalence of chronic renal failure against the background of grossly inadequate facilities for maintenance dialysis or renal transplantation. PMID- 1905473 TI - Norplant: a new contraceptive. AB - Norplant is a new method of birth control recently approved for use in the United States. It consists of flexible Silastic capsules filled with levonorgestrel, which are inserted subdermally on the inside of the upper arm. Norplant provides a near steady-state level of levonorgestrel for five years. It has been used in many European, South American and Asian countries, and in clinical studies in the United States. Norplant has an excellent continuation rate by users, and it is highly effective. It causes minimal adverse effects other than irregular menstrual patterns. PMID- 1905474 TI - Serum lipid and apolipoprotein concentrations in healthy men on diets enriched in either canola oil or safflower oil. AB - This randomized, blind study measured changes in serum lipid and apolipoprotein concentrations in 16 men consuming 39 +/- 1% of energy (en%) as fat either from safflower- or canola-oil-based diets for 8 wk. Initially, the men were stabilized for 3 wk on a typical American (baseline) diet. Compared with baseline, the vegetable-oil-based diets reduced serum total cholesterol 9-15% (P less than 0.002), low-density-lipoprotein (LDL)-cholesterol 12-20% (P less than 0.002), and apolipoprotein B-100 21-24% (P less than 0.001). There were no significant changes from baseline to the end of the study in serum triglycerides, total high density-lipoprotein (HDL) cholesterol, HDL3 cholesterol, HDL2 cholesterol, or apolipoprotein A-I. These data suggest that even if total fat intake remains at 39-40 en%, many men show lowered LDL cholesterol if saturated fatty acid intake is minimized and that diets high in polyunsaturated fatty acids do not necessarily lower HDL-cholesterol concentrations. PMID- 1905475 TI - Lack of dose response by dietary n-3 fatty acids at a constant ratio of n-3 to n 6 fatty acids in suppressing eicosanoid biosynthesis from arachidonic acid. AB - This study evaluated whether it is the ratio of n-3 to n-6 fatty acids or the absolute amount of n-3 fatty acids in diets that determines the degree of inhibition of eicosanoid biosynthesis from arachidonic acid (AA). Rats were fed diets containing different doses of linolenic acid or menhaden oil for 3 mo. Constant ratios of n-3 to n-6 fatty acids were maintained by concomitant increases in safflower oil as the n-6 fatty acid source. Results showed that AA concentrations in liver, platelet, and lung phospholipids and concentrations of eicosanoids synthesized in tissues were significantly (P less than 0.05) suppressed both by linolenic acid and menhaden oil; however, there was a lack of a dose response within groups fed different amounts of the same dietary fat. These results indicate that the ratio of n-3 to n-6 fatty acids in the diets, rather than the absolute amount of n-3 fatty acids, is the determining factor in inhibiting eicosanoid biosynthesis from AA. PMID- 1905476 TI - Milk-induced malabsorption in malnourished African patients. AB - Fifty malnourished rural African patients were randomly assigned to whole milk (50 g lactose/L), acidified milk (24 g lactose/L), or a commercial lactose-free diet (LFD) as a constant nasogastric infusion for 3 d, starting at 2 L/d and increasing to 3 L/d if tolerated. During the first 2 d mild symptoms of intolerance developed in 63% of patients on whole milk, 37% on acidified milk, and 54% on LFD whereas severe intolerance, necessitating withdrawal, was encountered in 22% receiving whole milk and none receiving LFD. Stool weights and fat excretion on day 3 were greater (P less than 0.02) in the remaining milk-fed patients whereas nitrogen balance remained strongly positive in all three groups. Eighty-seven percent of patients were methane producers, and high excretion rates were associated with better milk tolerance. The results suggest that although undiluted cow milk will not form a suitable tube feed for malnourished African patients, products such as acidified milk may prove cost effective. PMID- 1905477 TI - Technical and clinical testing of a computerized indirect calorimeter for use in mechanically ventilated neonates. AB - Testing of a proprietary indirect calorimeter (MGM, Jr.) was performed by using nitrogen displacement and added carbon dioxide to simulate oxygen consumption (VO2), carbon dioxide production (VCO2), and the respiratory quotient (RQ; VCO2/VO2). Errors in measured VO2, VCO2, and RQ were less than or equal to 2.5% when VO2 and VCO2 were 4-43 mL/min and flow rate was 100-2000 mL/min. The relative error in predicted VO2 was increased as the inspired oxygen concentration (FiO2) was raised but the error was less than 4% when the value of FiO2 minus expired oxygen concentration (FeO2) was greater than or equal to 0.015 and the FiO2 was less than or equal to 0.6. Sixteen studies were performed on seven very-low-birth-weight (VLBW), mechanically ventilated infants aged less than or equal to 11 d. VO2 was 8.37 +/- 1.81 mL.kg-1.min-1, VCO2 was 8.15 +/- 2.03 mL.kg-1.min-1, and RQ was 0.969 +/- 0.061 (means +/- SD). The MGM, Jr. is accurate for studies of low-birth-weight infants on mechanical ventilators when VO2 and VCO2 are greater than or equal to 4 mL/min, flow rate is less than or equal to 3000 mL/min, and FiO2 is less than or equal to 0.6. Clinical testing resulted in values similar to previously published data but the variability was higher. PMID- 1905478 TI - Effect of early introduction of formula vs fat-free parenteral nutrition on essential fatty acid status of preterm infants. AB - Previous studies have used relative (%) values of plasma 18:2n-6 (18:2 omega-6) and the ratio of 20:3n-9 to 20:4n-6 (triene/tetrene) to indicate the essential fatty acid (EFA: 18:2n-6 and 18:3n-3) status of preterm infants. The extent to which these indices reflect milligrams per liter quantities of n-6 and n-3 long chain polyunsaturated derivatives of EFA (LCPs), required for cell membrane accretion, is unknown. Thus, 18:2n-6, the triene-tetrene ratio, and n-6 and n-3 LCPs were measured in plasma phospholipid of preterm infants' cord blood (n = 22) and of preterm infants fed formula (n = 12) or of preterm infants who received fat-free parenteral nutrition (n = 15) on postnatal day 3. Whether expressed as percent or milligrams per liter, 18:2n-6 was markedly higher and the triene tetrene ratio lower in infants fed formula than in infants who had received no lipid. However, concentrations of n-6 and n-3 LCPs were similar in the two groups of infants and significantly higher than cord values. In the absence of an exogenous lipid source, it is suggested that tissue stores of LCPs are released in response to birth. PMID- 1905479 TI - Home care cost-effectiveness for respiratory technology-dependent children. AB - We evaluated home care costs and the cost-effectiveness of home care vs alternative institutional care for respiratory technology-dependent children in a Medicaid Model Waiver Program. "Cost-savings" was measured as the difference between the established Medicaid reimbursable charges to enact an individualized care plan at a long-term care institution and the actual Medicaid reimbursements for home care. Ten patients--six dependent on mechanical ventilation and four with a tracheostomy who were receiving oxygen--were included in the analysis. The mean (+/- SD) annual home care costs were $109,836 +/- $20,781 for ventilator dependent children and $63,650 +/- $12,350 for oxygen-dependent patients with a tracheostomy, representing annual savings of approximately $79,000 per patient and $83,000 per patient, respectively. The largest portion of home care reimbursements was for nursing care, accounting for 69.0% and 59.0% of the two patient groups. The full program (50 patients) has the potential for a savings of $4 million per year. PMID- 1905480 TI - Osseous metaplasia occurring in a benign colonic polyp. PMID- 1905481 TI - Apical and basolateral membrane conductances in the TBM cell line. AB - Cultured cell lines present several advantages over whole organ or ex vivo isolated epithelium for the physiological and biochemical study of epithelial transport. We have developed a new technique allowing for simultaneous intracellular and transepithelial electrophysiological measurements in the epithelium formed by a cultured cell line grown on thin collagen membranes. This technique was applied to the TBM 18/23 (toad bladder origin) cell line. The transepithelial and basolateral membrane potentials were -30 +/- 11 and -72 +/- 8 (SD) mV (n = 36), respectively. With the use of the effect of amiloride, which partially blocked the apical membrane conductance, and circuit analysis, the apical and basolateral membrane conductances were estimated to 0.7 +/- 0.1 and 2.8 +/- 0.4 mS/cm2, respectively. A sodium-selective conductive pathway was demonstrated in the apical membrane, and a barium-sensitive K(+)-selective conductance was shown to be present in the basolateral membrane. The basolateral membrane conductance was not modified by sudden inhibition of sodium transport by amiloride, but it was significantly reduced after a long-term decrease of Na+ transport. The cultured TBM cell line appears to be a convenient model to investigate the regulation of membrane ionic conductances in tight epithelia. PMID- 1905482 TI - Na(+)-Ca2+ exchangers from rod outer segments and cardiac sarcolemma: comparison of properties. AB - The properties of the Na(+)-Ca2+ exchangers from cardiac sarcolemma (SL) and rod outer segments (ROS) were studied in parallel by measuring the Na+ gradient dependent Ca2+ uptake into SL or ROS vesicles. The ROS exchanger, but not the SL exchanger, has a striking specific dependence on K+. The ROS exchanger is stimulated by K+ with an apparent concentration at half-maximum of 1 mM. The addition of valinomycin, to produce an inside-positive membrane potential, stimulates the SL exchanger 1.8-fold and the ROS exchanger 1.2-fold. The Michaelis constant for half-maximal transport rate for Ca2+ and the maximal transport rate for the exchangers, in the absence of valinomycin, are estimated to be 20 microM and 8 nmol.mg-1.2.2 s-1 in SL and 5 microM and 1 nmol.mg-1.2.2 s 1 in ROS. Both exchangers are modulated by the same regulatory influences. For example, both are stimulated by proteases, phospholipase D, and intravesicular Ca2+. PMID- 1905483 TI - Stimulation of Ca2+ influx by endothelin-1 is subject to negative feedback by elevated intracellular Ca2+. AB - Endothelin-1 (ET-1) has been shown to require Ca2+ influx for activation of vascular smooth muscle in vivo, but in vitro models show that ET-1 mobilizes intracellular Ca2+ and is independent of extracellular Ca2+. We present data that suggest ET-1 modulates cellular responses through a dual mechanism involving both phosphatidylinositol turnover and Ca2+ channel activation. Addition of low concentrations of ET-1 (less than 10(-9) M) to serum-deprived quiescent Rat-1 cells stimulated Ca2+ influx while having little effect on diacylglycerol (DG) release or intracellular Ca2+ levels. In contrast, higher concentrations of ET-1 (greater than 10(-9) M) stimulated intracellular Ca2+ transients and release of inositol trisphosphate (IP3) and DG but did not activate Ca2+ uptake. Stimulation of Ca2+ influx at low [ET-1] could not be accounted for by depletion of intracellular IP3-sensitive pools. Neither the stimulation of Ca2+ influx at low [ET-1] nor the inhibitory actions of high [ET-1] could be mimicked by the activation of protein kinase C. We tested the hypothesis that elevated intracellular Ca2+ was inhibitory for Ca2+ influx. When intracellular Ca2+ transients were maintained below approximately 165 nM by chelation with BAPTA or BAPTA derivatives with altered affinity for Ca2+, Ca2+ influx was stimulated over the entire range of ET-1 concentrations. In addition, experimentally elevating intracellular Ca2+ levels with the tumor promoter thapsigargin abolished ET-1 stimulated Ca2+ influx. These data suggest that the biological consequences of ET 1 release may be determined by local concentration differences. Thus in vascular smooth muscle cells ET-1 may act either to mobilize intracellular Ca2+ or to promote Ca2+ influx, depending on the distance from the endothelial cell source in the vascular wall. The activation of different processes by low and high ET-1 concentrations may determine the physiological response to ET-1 stimulation in vivo. PMID- 1905484 TI - Toad urinary bladder epithelial cells contain an analogue of cytoskeletal protein 4.1. AB - Epithelial cell polarity and vectorial transport require cytoskeletal proteins that maintain local cell membrane structure and mediate cytoplasmic vesicle movement. The cytoskeleton of leaky epithelia, such as the intestinal mucosa and renal proximal tubule cells, has been extensively studied. However, cytoskeletal studies in tight epithelia such as the mammalian collecting duct and toad urinary bladder generally have been confined to ultrastructural investigation. Recent research in nonepithelial cell types has identified an interesting family of cytoskeletal proteins. Present in multiple cell types, these protein 4.1 analogues share a number of similar functional characteristics, yet are structurally diverse. They are multiply phosphorylated by several different kinases, and phosphorylation regulates their associations with other cytoskeletal constituents, integral membrane components, and cytoplasmic vesicles. Using a combination of immunochemical and immunofluorescent techniques, we have demonstrated that toad bladder epithelial cells contain a 65-kDa analogue of human erythrocyte protein 4.1. Toad bladder epithelial cell protein 4.1 is structurally similar to its erythrocyte counterpart and is phosphorylated. This protein 4.1 species is present throughout the toad bladder granular cell cytoplasm, suggesting that it participates in multiple granular cell functions. PMID- 1905485 TI - Role of glucocorticoid in the regulation of glycogen metabolism in skeletal muscle. AB - With the use of the hindlimb perfusion technique, the effect of glucocorticoid on the regulation of glycogen metabolism was studied in rat skeletal muscle. Rats were adrenalectomized (ADX) or sham operated (controls) 14 days before the study. The ADX animals were treated with either saline or corticosterone, and the hindlimbs were perfused at rest or during muscle contraction with saline or epinephrine (10(-7) M). In the resting state, the glycogen content was 33.0 +/- 1.9 mumol/g in the controls, and the activity ratios of glycogen phosphorylase (GPase) and glycogen synthase (GSase) were 0.27 +/- 0.03 and 0.15 +/- 0.02, respectively. Epinephrine treatment increased GPase activity (0.78 +/- 0.03) and decreased GSase activity (0.05 +/- 0.01), which resulted in decreased glycogen content (25.7 +/- 0.9 mumol/g; P less than 0.01). Adrenalectomy induced a 35% reduction in glycogen content but had no effect on the activities of basal enzymes. Under these conditions, however, epinephrine had no effect on GPase activity, had a diminished effect on GSase activity (0.11 +/- 0.01), and did not induce further glycogen breakdown. Corticosterone replacement normalized muscle glycogen content in ADX rats as well as the response of the enzymes to epinephrine. Muscle contraction resulted in a decrease in glycogen content (8.9 +/- 1.3 mumol/g) and in GPase activity (0.14 +/- 0.02) and an increase in GSase activity (0.25 +/- 0.01); this was not affected by adrenalectomy nor by epinephrine. In conclusion, these data indicate that glucocorticoid is essential for the effects of epinephrine on GPase activation. on GSase inhibition, and consequently on glycogen breakdown in resting muscle.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1905486 TI - Hormone secretion stimulated by ethanol-induced cell swelling in normal rat adenohypophysial cells. AB - Ethanol has been reported to affect endocrine functions, but its mechanism of action is unclear. To evaluate the hypothesis that cell swelling induced by ethanol permeation through the plasmalemma triggers hormone secretion, we studied the effect of ethanol on both hormone secretion and cell volume in acutely dispersed rat adenohypophysial cells under isotonic and hypertonic conditions. Isotonic ethanol caused a prompt cell swelling and an explosive secretory burst of prolactin and thyrotropin, which were proportional to the concentration of ethanol between 10 and 120 mM. The lowest effective dose of isotonic ethanol was 10 mM, which is below the plasma levels of legal intoxication (16 mM). Removal of medium Ca2+ enhanced the isotonic ethanol-induced increases in both cell volume and secretion. Hypertonic ethanol was ineffective in these effects. These data indicate that, in normal rat adenohypophysial cells, cell swelling caused by the rapid passage of ethanol through the plasmalemma is a potent mechanism for stimulating hormone secretion and this induced secretion is negatively modulated by extracellular Ca2+. PMID- 1905488 TI - Sulfation by human lung fibroblasts: SO4(2-) and sulfur-containing amino acids as sources for macromolecular sulfation. AB - Studies were carried out in human lung fibroblasts (IMR-90) to investigate 1) the relative contribution of two extracellular pools, inorganic sulfate and sulfur containing amino acids, to the intracellular fraction precipitable by trichloroacetic acid and 2) the possibility that the transport of these sulfur containing substrates at the plasma membrane may be a limiting step for macromolecular sulfation. Our studies indicate that the ability to use SO4(2-) released by intracellular catabolism of the sulfur-containing amino acid L cysteine differs from one cell system to another. In contrast to smooth muscle cells, in the human lung fibroblast, L-cysteine contributes significantly to the intercellular pool of SO4(2-) used for sulfation at extracellular [SO4(2-)] less than 100 microM. However, under physiological conditions with respect to SO4(2-) ([SO4(2-)]0 = 300 microM), L-cysteine does not contribute greater than 30% of the sulfate incorporated into the cellular fraction. Taurine (2-aminoethanesulfonic acid) inhibits SO4(2-) incorporation into the cell-associated macromolecular fraction. However, results suggest that the effect is not due to either SO4(2-) released by its catabolism or to an effect on SO4(2-) transport into the cell. The fact that the transport inhibitor 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid inhibits sulfate incorporation indicates that carrier-mediated sulfate transport at the cellular plasma membrane may be a limiting step for sulfate incorporation. In conclusion, under physiological conditions with respect to SO4(2-), inorganic sulfate is a major source of sulfate for sulfation in human lung fibroblasts and macromolecular sulfation may be limited by its transport into the cells. PMID- 1905487 TI - Myosin phosphorylation and calcium in tonic and phasic contractions of colonic smooth muscle. AB - The time dependence of lightly loaded shortening velocity, myosin phosphorylation, and changes in myoplasmic Ca2+ concentration ([Ca2+]i) were measured during tonic and phasic contractions of circular smooth muscle from the proximal colon of the dog. Shortening velocity was measured by quick release to a 10% afterload. Myosin phosphorylation was measured by an immunoblot method, and changes in [Ca2+]i were estimated by measuring fluorescence intensity at 550 nm in muscle strips loaded with fluo-3. During tonic contractions induced by 60 mM K+, phosphorylation increased monotonically from 0.11 +/- 0.011 to 0.29 +/- 0.015 mol Pi/mol light chain at 10 min. In contrast, lightly loaded shortening velocity increased rapidly within 10 s to 0.042 +/- 0.003 lengths/s and decreased exponentially to 0.013 +/- 0.001 lengths/s at 15 min. During transient contractions induced by 100 microM acetylcholine, phosphorylation increased from 0.16 +/- 0.03 to 0.30 +/- 0.06 mol Pi/mol light chain at 19 s. In contrast, shortening velocity increased to 0.068 +/- 0.015 lengths/s within 2.4 s and decreased significantly to 0.027 +/- 0.009 lengths/s at 22 s. Fluo-3 fluorescence increased in parallel with force during both tonic and transient contractions. In a smooth muscle that is able to contract both tonically and phasically we observed transient increases in shortening velocity without concurrent phosphorylation or [Ca2+]i transients. Therefore, there are factors in addition to myosin phosphorylation or changes in [Ca2+]i that regulate cross-bridge cycling rates in both tonic and phasic contractions. PMID- 1905489 TI - Exogenous prostacyclin does not sensitize arterial baroreceptors. AB - It has been shown that prostacyclin (PGI2) sensitizes cardiac receptors. However, the effects of PGI2 on arterial baroreceptors are not well understood. In rabbits anesthetized with alpha-chloralose (n = 12), we examined reflex changes in multiunit efferent renal sympathetic nerve activity (RSNA) during hypotension caused by intravenous PGI2 (0.1, 0.2, 0.5, 1.0, 2.0 micrograms/kg), nitroglycerin (NG; 5, 10, 20, 50, 100 micrograms/kg), and sodium nitroprusside (SNP; 5, 10, 20, 50, 100 micrograms/kg) before and after bilateral vagotomy. Before vagotomy, RSNA increased during hypotension caused by NG or SNP (P less than 0.01) but did not significantly change during comparable hypotension caused by PGI2. After vagotomy, PGI2 increased RSNA as much as NG or SNP. In another group (n = 6), we examined the changes in aortic pressure (AoP), multiunit afferent aortic nerve activity (ANA), and the aortic diameter (AoD) during hypotension caused by intravenous PGI2, NG, and SNP. The relationship between changes in AoP and those in ANA did not differ during hypotension caused by the three drugs. The relationship between changes in AoP and those in AoD and that between changes in AoD and those in ANA also did not differ. Finally, we examined changes in AoP, ANA, and AoD during ramp increases or decreases of AoP caused by intravenous angiotensin II or NG under background infusion of saline, PGI2, or SNP (n = 6). The relationship among these variables did not differ during infusion of PGI2 and SNP. These results suggest that PGI2 stimulates cardiac receptors with vagal afferents but does not sensitize arterial baroreceptors. PMID- 1905490 TI - Assessment of elastin and collagen contribution to aortic elasticity in conscious dogs. AB - The elastic behavior of total elastin (EE) and collagen (EC) and the recruitment of collagen fibers (FC) supporting wall stress at a given transmural pressure level were assessed in seven conscious dogs using descending thoracic aortic pressure (microtransducer) and diameter (sonomicrometer) measurements. Stress strain relationships values calculated at control and during bolus administration of angiotensin and nitroglycerin enabled quantification of angiotensin and nitroglycerin enabled quantification of elastic moduli of elastin (EE = 4.868 +/- 1.753 x 10(6) dyn/cm2; means +/- SD) and collagen (EC = 1,306 +/- 637 x 10(6) dyn/cm2) according to a biphasic model of elastin and collagen parallel arrangement. The FC was found to be 6.1 +/- 2.6% at a pressure level of 118 +/- 16 mmHg. Values for EE and EC were similar to those reported in in vitro studies and showed scarce variability. This approach provides a quantitative evaluation of elastin and collagen moduli in conscious animals and also permits the evaluation of FC, which may be of interest in studies of connective tissue diseases involving the aortic wall. PMID- 1905491 TI - Hyperpolarization of arterial smooth muscle induced by endothelial humoral substances. AB - A sandwich preparation was obtained by placing a segment of the endothelium-free guinea pig coronary artery over the intact carotid artery with the objective being to determine whether the endothelium-dependent hyperpolarization by acetylcholine chloride (ACh) is mediated by a humoral factor. ACh hyperpolarized the sandwiched coronary smooth muscle membrane, the amplitude being larger than that of the carotid artery and smaller than that of the intact coronary artery. When spontaneously active smooth muscles (stomach antrum or portal vein) were used as the donor tissue, no electrical signal was transducted to the overlying coronary smooth muscles. In the sandwiched coronary artery, the ACh-induced hyperpolarization was not inhibited by ouabain, indomethacin, or nitroarginine. Pinacidil hyperpolarized the coronary smooth muscle membrane; the responses were inhibited by glybenclamide but not by tetraethylammonium chloride (TEA). The ACh induced hyperpolarization was inhibited by TEA but not by glybenclamide. These results suggest that the ACh-induced hyperpolarization is mediated by an endothelium-derived humoral substance (endothelium-derived hyperpolarizing factor). Possible contribution of Ca-dependent K channels, but not ATP-sensitive K channels, to the endothelium-derived hyperpolarizing factor-induced hyperpolarization was considered. PMID- 1905492 TI - Convergence of sympathetic, vagal, and other sensory inputs onto neurons in feline ventrolateral medulla. AB - Responses of 80 neurons in rostral and caudal ventrolateral medulla to multiple sources of sensory input were assessed in cats anesthetized with alpha chloralose. Sixty-one of eighty-one neurons (76%) were excited by stimulation of the stellate ganglion, and one neuron exhibited inhibition followed by excitation. In response to vagal stimulation, 12% of the neurons were excited and 29% inhibited. Vagal stimulation reduced the responses of 13 of 39 (33%) neurons to sympathetic stimulation. Overall, one-third of the neurons responded to both sympathetic and vagal stimulation. There was no difference in proportion of responsive neurons in rostral versus caudal ventrolateral reticular formation. Cells were also tested for auditory, visual, and natural somatic stimuli. Ten percent of the neurons responded to all five stimuli, and another 25% responded to four stimuli. Twelve percent of neurons were unresponsive to any stimulus. Twenty cells were tested for responses to changes in blood pressure elicited with phenylephrine and nitroglycerin. Seven neurons were inhibited by increases or excited by decreases in pressure, four had the opposite responses, and nine were unresponsive. In general, blood pressure-sensitive cells exhibited comparable convergence of other inputs as the overall cell population. However, three times as many pressure-insensitive neurons received vagal input as did pressure sensitive neurons. In conclusion, neurons in the ventrolateral medulla, including the vasopressor and vasodepressor regions, receive and integrate convergent input from multiple sensory origins. Since the regions of the reticular formation studied are functionally heterogeneous, the precise functions of these neurons are not known. PMID- 1905493 TI - Endothelial albumin permeability is shear dependent, time dependent, and reversible. AB - Altered permeability of vascular endothelium to macromolecules may play a role in vascular disease as well as vascular homeostasis. Because the shear stress of flowing blood on the vascular wall is known to influence many endothelial cell properties, an in vitro system to measure transendothelial permeability (Pe) to fluorescein isothiocyanate conjugated bovine serum albumin under defined physiological levels of steady laminar shear stress was developed. Bovine aortic endothelial cells grown on polycarbonate filters pretreated with gelatin and fibronectin constituted the model system. Onset of 1 dyn/cm2 shear stress resulted in a Pe rise from 5.1 +/- 1.3 x 10(-6) cm/s to 21.9 +/- 4.6 X 10(-6) cm/s at 60 min (n = 6); while 10 dyn/cm2 shear stress increased Pe from 4.8 +/- 1.5 X 10(-6) cm/s to 50.2 +/- 6.8 X 10(-6) cm/s at 30 min and 49.6 +/- 8.9 X 10( 6) cm/s at 60 (n = 9). Pe returned to preshear values within 120 and 60 min after removal of 1 and 10 dyn/cm2 shear stress, respectively. The data show that endothelial cell Pe in vitro is acutely sensitive to shear stress. PMID- 1905494 TI - 31P-NMR study of normoxic and anoxic perfused turtle heart during graded CO2 and lactic acidosis. AB - We studied the effects of graded acidosis (both CO2 and lactic acid) and anoxia on intracellular pH (pHi) regulation, high-energy phosphates, and mechanical function of isolated perfused hearts of the turtle (Chrysemys picta bellii) at 20 degrees C using 31P-nuclear magnetic resonance (NMR) spectroscopy. During CO2 acidosis, anoxia had no effect on apparent nonbicarbonate buffer value (d[HCO3 ]/dpHi = 71 and 89 mM/pH in normoxia and anoxia, respectively) or on pHi regulation (dpHi/dpHe = 0.52 and 0.43 in normoxia and anoxia, respectively, where pHe is extracellular pH). During normoxic lactic acidosis, dpHi/dpHe was similar to the values observed in CO2 acidosis and averaged 0.55 overall. During anoxic lactic acidosis, however, similar regulation occurred over only a narrow range of pHe, and then dpHi/dpHe increased to greater than 1.0 at pHe less than 7.1. Creatine phosphate (CP), calculated as the area of the NMR peak, fell more in response to normoxic CO2 acidosis than to normoxic lactic acidosis; in anoxia, the fall in CP was further increased but to similar extreme levels (10-20% of control) in both acid perfusions. Cardiac output and maximum rate of pressure development each fell during acidosis in similar fashion in all protocols, and the responses were similar in normoxic and anoxic hearts. Heart rate, in contrast, decreased during acidosis, but this effect was more pronounced when hearts were anoxic. We conclude that the effect of acidosis on cardiac function can depend on the type of acidosis imposed. Based on the heart's insensitivity to anoxia alone, we suggest that anoxia may normally depress function indirectly via its effect on intracellular acid-base state. PMID- 1905495 TI - Acute phase response in exercise. II. Associations between vitamin E, cytokines, and muscle proteolysis. AB - Cytokines such as interleukin 1 (IL-1), tumor necrosis factor-alpha (TNF-alpha), and interleukin 6 (IL-6) mediate a variety of host responses to trauma and infection, including skeletal muscle proteolysis. This investigation assesses the influence of damaging eccentric exercise on in vitro production and plasma concentrations of cytokines and their relationship to muscle protein breakdown. In a double-blind placebo-controlled protocol, 21 male subjects took vitamin E supplements (800 IU/day) for 48 days, then ran downhill on an inclined treadmill. Twenty-four hours after this single session of eccentric exercise, endotoxin induced secretion of IL-1 beta was augmented 154% (P less than 0.01) in cells obtained from the placebo subjects, but no significant exercise-related changes were observed in cells from the vitamin E-supplemented subjects. TNF-alpha secretion was also significantly increased 24 h after exercise, but the response was not inhibited by vitamin E. In contrast, IL-6 secretion did not change after exercise, but dietary vitamin E supplementation significantly reduced IL-6 secretion throughout the 12-day period of observation (P = 0.023). Urinary 3 methylhistidine excretion correlated with mononuclear cell secretion of both IL-1 beta (P less than 0.05) and prostaglandin E2 (P less than 0.05), supporting the concept that these mononuclear cell products contribute to the regulation of muscle proteolysis. PMID- 1905496 TI - Model to facilitate studying oxygen and carbon dioxide transport. AB - A simple model has been constructed for microcomputer (PC) simulations involving basic cardiopulmonary principles of oxygen transport. Students can change parameters such as metabolic rate, blood hemoglobin concentration, barometric pressure, air composition, etc., and study parameter effects on blood gas concentrations and partial pressures. An important feature of the model program is that there are no negative feedback controls to maintain homeostasis. However, after a perturbation has been introduced, adjustments can be made to appropriate variables to correct for abnormal effects. For example, ventilation rate and blood hemoglobin concentration might be adjusted to compensate for low atmospheric oxygen. Because these do not change automatically in the model program, learning is enhanced when the student has to make the appropriate adjustments needed to correct disturbances in the blood gases that follow a perturbation. PMID- 1905497 TI - Fibrillary (immunotactoid) glomerulopathy. A possible role for kappa light chain in its etiology and/or pathogenesis. AB - The initial clinical manifestations, course, and immunopathologic findings of renal biopsies of nine patients with fibrillary glomerulopathy are reported. Their first symptoms and courses were variable, but proteinuria and renal failure were common. While some patients required hemodialysis soon after coming for treatment, others progressed to renal failure over several years. Three patients had monoclonal gammopathy; one of them had an isolated, transient, Bence-Jones proteinuria. The main pathologic features are glomerular enlargement, mesangial expansion, and mild hypercellularity. Congo red and thioflavin stains were negative. Kappa chain, either alone or with lambda chain and IgG, were the predominant immunoreactants. Ultrastructurally, the presence of coarse fibrils of 15-25 nm was characteristic, but there were also granular deposits in the capillary wall that occurred in a band-like pattern in the inner half of the glomerular basement membrane in a manner similar to the deposits seen in light chain deposit disease. The immunofluorescence and ultrastructural findings suggest that light chains (especially kappa) may be significant in the pathogenesis of fibrillary glomerulopathy and that there may be a relationship with light chain deposit disease. PMID- 1905498 TI - [Prenatal diagnosis of lysosomal storage disease in the USSR]. PMID- 1905499 TI - Effect of dihydrotestosterone on the rate of ethanol elimination in healthy men. AB - Testosterone (T) and, more potently, dihydrotestosterone (DHT), are in vitro inhibitors of hepatic alcohol dehydrogenase (ADH). An increase in the rate of ethanol disappearance (RED) in man has been observed after orchidectomy. We thus investigated the influence of DHT administration on RED in 10 healthy male volunteers. RED was estimated after an oral ethanol bolus (0.6 g/kg), before and after a 14-day treatment with DHT (2 x 125 mg per day percutaneously; Andractim, Besins iscovesco, France). A mean 11.5-fold increase in DHT levels and a 2.0-fold decrease in T values were observed after DHT administration, confirming the good compliance with treatment. RED was decreased after DHT (0.168 +/- 0.043 vs. 0.137 +/- 0.043 g/l/hr; mean +/- SD; p less than 0.01 using Wilcoxon's paired comparison test). These data are consistent with a DHT-induced inhibition of hepatic ADH in vivo. This could have a beneficial effect by decreasing acetaldehyde production in alcoholic patients, in whom marked hypoandrogenism frequently occurs. PMID- 1905500 TI - [Direct re-instillation through endotracheal intubation tubes during enteral nutrition for short bowel syndrome]. AB - Case report of a 65-year-old man, operated on for small bowel infarction. Only the initial 40 cm of the jejunum, and the last 10 cm of the ileum were vital and could be kept. The ileo-caecal valve and the colon were not resected. Two stomas were carried out: a left-sided jejunostomy, and a right-sided ileostomy. Enteral nutrition was attempted, but jejunal outflow increased. It was therefore decided to attempt re-instillation of jejunal juices directly to the ileum using two 33 CH endotracheal tubes connected with soft chest drain tubing. A bag was placed over the jejunal tube to collect any leakage. Semi-elemental enteral nutrition could then be successfully carried out, and parenteral feeding stopped. With this simple appliance, the patient was able to lead as normal a life as possible. After 42 days of such feeding, the patient had only lost 2 kg in body weight, and intestinal continuity was re-established. PMID- 1905502 TI - Analysis of anesthetic action on the potassium channels of the Shaker mutant of Drosophila. AB - Recent evidence suggest that exposure to volatile anesthetic agents causes a change in conductance through an undelineated potassium channel. With recently developed genetic and molecular techniques the Drosophila melanogaster (D.m.) genome can be manipulated to study the role that potassium ion channel function plays in anesthetic action. The IA potassium channel is encoded by the Shaker (Sh) locus on the X chromosome of D.m. Because this channel may be one of those involved in volatile anesthetic action, we tested the sensitivity to isoflurane in three Shaker strains with different degrees of dysfunctional IA conductance (Shnull greater than ShKS133 greater than Sh5). Anesthetic sensitivity was also examined in mutant strains of D.m. which express abnormalities either in other potassium channel conductances (eag, slo) or other ion conductances (para). The normally conducting wild type served as the control. Two-day-old adult D.m. were stimulated with a heat source during exposure to the volatile anesthetic isoflurane, and the number moving in response to the noxious stimulus was noted. After testing the Shaker and control strains at no fewer than 13 concentrations, the IC50S (isoflurane concentration in percent vol/vol at which 50% of the flies did not respond to the heat stimulus) were derived. The IC50 values for Sh 5 (0.89), Sh133 (1.29), and Shnull (1.37) were significantly different from the wild type (0.56). The rank order of insensitivity of these Shaker mutants corresponded to the extent of the alteration in IA conductance as established by previous studies in these mutants. Neither eag (0.66), para (0.48), nor slo (0.63) differed significantly from the wild type. These data suggest that the IA potassium channel plays a role in volatile anesthetic action. PMID- 1905501 TI - Misoprostol compared with sucralfate in the prevention of nonsteroidal anti inflammatory drug-induced gastric ulcer. A randomized, controlled trial. AB - OBJECTIVES: To compare the efficacy and frequency of adverse experiences of misoprostol and sucralfate in the prevention of gastric ulcers in patients receiving nonsteroidal anti-inflammatory drug (NSAID) therapy. DESIGN: A prospective, randomized, single-blind, multicenter trial. PATIENTS: Patients with osteoarthritis receiving treatment with ibuprofen, piroxicam, or naproxen and experiencing abdominal pain were eligible. INTERVENTIONS: Patients who were expected to receive at least 3 months of NSAID therapy and who did not have a gastric ulcer at the time of the initial screening endoscopy were randomized to receive misoprostol, 200 micrograms four times a day, or sucralfate, 1 g four times a day. A gastric ulcer was defined as a lesion of the gastric mucosa 0.3 cm or greater in diameter. Patients were followed clinically, and repeat endoscopies were performed after 4, 8, and 12 weeks. MAIN MEASUREMENT: The development of a gastric ulcer, which was regarded as a prophylaxis failure. RESULTS: Two hundred fifty-three patients were evaluable for efficacy analysis. A gastric ulcer developed in 2 of the 122 (1.6%, 95% CI, 0.3% to 6.4%) patients on misoprostol, compared with 21 of 131 patients on sucralfate (16%, CI, 10.4% to 23.7%). The difference in ulcer rates was 14.4% (CI, 10.4% to 19.5%; P less than 0.001). CONCLUSION: In patients receiving chronic NSAID therapy for osteoarthritis, treatment with misoprostol for 3 months was associated with a significantly lower frequency of gastric ulcer formation, compared with treatment with sucralfate (P less than 0.001). PMID- 1905503 TI - New mutants of Drosophila that are resistant to the anesthetic effects of halothane. PMID- 1905505 TI - Chromosome damage induced by ethanol. PMID- 1905504 TI - Formation of a 37 kilodalton liver protein-acetaldehyde adduct in vivo and in liver cell culture during chronic alcohol exposure. AB - With the use of antibodies that can recognize acetaldehyde adducts and the application of various immunological techniques, several protein-AAs have now been shown to form in vivo during chronic alcohol ingestion. These protein-AAs include the 37-kDa liver protein-AA, the CytP450IIE1-AA, hemoglobin-AA, two serum protein-AAs with molecular weights of 50 kDa and 103 kDa, and collagen type I protein-AA in liver. If acetaldehyde is the agent responsible for alcoholic liver injury, acetaldehyde toxicity in chronic alcohol ingestion must be linked to the ability of acetaldehyde to form adducts with proteins and perhaps other macromolecules. This is at least one mechanism of acetaldehyde-mediated liver injury. For proteins that serve critical functions, acetaldehyde adduct formation may alter their functions and thereby produce organ damage. Acetaldehyde adduct formation can also elicit humoral or cytotoxic immune responses and these responses may also lead to organ injury. PMID- 1905506 TI - Effects of insulin-like growth factor I and growth hormone in cultured human granulosa cells. AB - Human granulosa cells, obtained either from natural or stimulated cycles, were cultured, and the response to IGF-I and GH was analyzed. It was found that IGF-I alone stimulated thymidine incorporation in both types of granulosa cells. Furthermore, IGF-I alone and in combination with FSH or LH enhanced estradiol and progesterone production. In a limited series of experiments, GH in combination with FSH was found to stimulate steroidogenesis in granulosa cells obtained from natural, but not from stimulated, cycles. PMID- 1905507 TI - Contraceptive implants. PMID- 1905508 TI - Indications for GnRH agonists in an in vitro fertilization program. PMID- 1905509 TI - Synergistic effect of growth hormone and gonadotropins in achieving conception in "clonidine-negative" patients with unexplained infertility. AB - Based on preliminary reports by others and by us of a potentiating effect of growth hormone (GH) on human menopausal gonadotropin (hMG)-induced ovulation, a study using a randomized, prospective, cross-over protocol between GH + hMG/human chorionic gonadotropin (hCG) and hMG/hCG was undertaken. The study included patients with long-standing (2-11 years) unexplained infertility with a negative or reduced GH response to clonidine (up to 150 micrograms of clonidine orally). The first cycle was randomly assigned between GH/hMG/hCG (study cycle) and hMG/hCG alone (control cycle), and after an interval cycle the patient's treatment was crossed over. All patients who completed the study had previously undergone 1-20 attempts at ovulation induction for in vitro fertilization (IVF) and 5-40 cycles of ovulation induction for in vivo fertilization at three different medical centers. Three patients conceived on the combined GH/hMG cycle, with diminution in the hMG consumption needed for ovulation induction in the study cycles. Another patient with long-standing mechanical infertility underwent 11 abortive attempts at ovulation induction with hMG for IVF but has never achieved egg retrieval. On the GH/hMG/hCG ovulation induction cycle, three mature ova were retrieved as opposed to no response and cancellation of the "hMG only" cycle. Another patient with 11 years of primary infertility who had undergone 21 previous attempts at ovulation induction and had reached follicular aspiration in only three of those cycles conceived spontaneously on the first cycle after the GH/hMG/hCG IVF/ET cycle. All four pregnancies that have been achieved by now in seven GH/hMG-treated patients ended in cesarean deliveries of four normal male neonates. No correlation was found between the follicular fluid levels of insulin like growth factor I (IGF-I) and the fertilization rate in vitro. The peripheral IGF-I levels were significantly higher during the follicular phase of the study cycles than during the respective stage of the control cycles or the luteal phase of either cycle. A study of serum GH-binding protein (GH-BP) levels revealed gradual increases in the late follicular phase, in the luteal phase, and in early pregnancy. On the basis of this study and in keeping with earlier reports, we conclude that the addition of GH to hMG/hCG may serve as a contributory adjunct in selected patients. However, in contrast to others who could not find a correlation between the response to acute tests for GH release and the ovarian response to combined treatment, we conclude that the clonidine test can play a discriminatory role in identifying patients who may benefit from this innovative combination. PMID- 1905510 TI - Levonorgestrel-releasing intrauterine device. PMID- 1905511 TI - Intrauterine insemination. PMID- 1905512 TI - Alterations and reversibility of the effects of gossypol acetic acid on the intestinal uptake of end product nutrients in normal and protein calorie malnourished male rats. AB - The effects of gossypol acetic acid, an experimental male antifertility agent, 20 mg/kg body weight daily for 15 days and its subsequent withdrawal have been investigated on the intestinal uptake of certain end product nutrients, namely glucose, leucine, alanine and calcium, in normal and protein-calorie-malnourished (PCM) male albino rats. Gossypol feeding caused a reduction in body weight, intestinal weight and length, protein and nucleic acid contents in both normal and PCM animals. Serum parameters, e.g. total protein, albumin and globulin, also showed a decrease in PCM rats. PCM per se considerably elevated the uptake of nutrients but gossypol feeding inhibited the uptake of nutrients both in normal fed and malnourished animals. Gossypol caused a decrease in the Na(+)-dependent (active) glucose uptake while the Na(+)-independent (passive) process was not altered. The kinetic parameters of glucose uptake indicate that gossypol might be interfering with the transport/carrier protein of these nutrients as reduction in maximum uptake velocity (Jmax) of these systems was observed without, however, any change in the affinity constant (Kt). PMID- 1905513 TI - Production and properties of xylanases from thermophilic actinomycetes. AB - 30 strains of xylanolytic thermophilic actinomycetes were isolated from composted grass and cattle manure and identified as members of the genera Thermomonospora, Saccharomonospora, Microbispora, Streptomyces and Actinomadura. Screening of these strains for extracellular xylanase indicated that strains of Saccharomonospora and Microbispora generally were poor xylanase producers (0.5 1.5 U/ml) whereas relatively high activities were observed in cultures of Streptomyces and Actinomadura (4-12 U/ml). A preliminary characterization of the enzymes of strains of the latter genera suggested that xylanases of all the strains of Actinomadura exhibited higher thermostabilities than those of Streptomyces. To evaluate the potential of thermophilic Actinomadura for industrial applications, xylanases of three strains were studied in more detail. The highest activity levels for xylanases were observed in cultures grown on xylan and wheat bran. The optimal pH and temperature for xylanase activities ranged from 6.0 to 7.0 and 70 to 80 degrees C. The enzymes exhibited considerable thermostability at their optimum temperature. The half-lives at 75 degrees C were in the range from 6.5 to 17 h. Hydrolysis of xylan by extracellular xylanases yielded xylobiose, xylose and arabinose as principal products. Estimated by the amount of reducing sugars liberated the degree of hydrolysis was 55 to 65%. Complete utilization of xylan is presumably achieved by beta-xylosidase activities which could be shown to be largely cell-associated in the 3 Actinomadura strains. PMID- 1905514 TI - Fine-structural and chemical analyses on inner and outer sheath of the cyanobacterium Gloeothece sp. PCC 6909. AB - Cells of the unicellular cyanobacterium Gloeothece sp. PCC 6909 are surrounded by an inner (enclosing 1-2 cells) and an outer (enclosing cell groups) sheath. Using conventional Epon-embedding in combination with ruthenium-red staining, the inner and outer sheaths appeared similar and displayed multiple bands of electron-dense subunits. However, embedding in Nanoplast resin to avoid shrinkage led to the detection of two distinct zones (inner and outer zone) each with several distinct layers. The zone delimited by the electron-dense thick inner sheath layer, and the zone enclosed by the thin electron-dense outer sheath layer, are composed of a homogeneous material of little electron-contrast. Whereas the outer zone appears to be of even contrast, the inner zone is characterized by a distinct electron-transparent layer. Element distribution analysis revealed that the electron-transparent layer contained relatively large amounts of sulfur, carbon, and oxygen but only little nitrogen. Inner and outer sheath fractions were isolated by differential mechanical cell breakage and centrifugation. The outer sheath fraction was less hydrated than the inner one. The two fractions differed little in their contents of uronic acids, carbohydrate and protein, although the outer sheath fraction contained less sulfate. A soluble polysaccharide with a chemical composition similar to that of inner and outer sheath fractions was also obtained from the culture supernatant. PMID- 1905515 TI - Trajectory of aerosol droplets from a sprayed bacterial suspension. AB - Simulated droplet trajectories of a polydispersed microbial aerosol in a laminar air flow regimen were compared with observed dispersal patterns of aerosolized Bacillus subtilis subsp. niger spores in quasilaminar airflow. Simulated dispersal patterns could be explained in terms of initial droplet sizes and whether the droplets evaporated to residual aeroplanktonic size before settling to the ground. For droplets that evaporated prior to settling out, a vertical downwind size fractionation is predicted in which the microbial residue of the smallest droplets settles the least, and is found in the airstream at about sprayer height, and progressively larger droplet residues settle to progressively lower heights. Observations of spore particle size distributions downwind from a spray source support the simulation. Droplet and particle size distributions near the source had three size fractions: one containing large, presumably nonevaporated droplets of greater than or equal to 7 microns in diameter, and two smaller fractions, with diameters of 2 to 3 microns (probably the residue of droplets containing more than one spore) and 1 to 2 microns (probably the residue from single-spore droplets). As predicted by the simulation, the aerosol settled and progressed downwind, with the number of small droplets and particles increasing in proportion to the height and distance downwind. PMID- 1905516 TI - Product toxicity and cometabolic competitive inhibition modeling of chloroform and trichloroethylene transformation by methanotrophic resting cells. AB - The rate and capacity for chloroform (CF) and trichloroethylene (TCE) transformation by a mixed methanotrophic culture of resting cells (no exogenous energy source) and formate-fed cells were measured. As reported previously for TCE, formate addition resulted in an increased CF transformation rate (0.35 day-1 for resting cells and 1.5 day-1 for formate-fed cells) and transformation capacity (0.0065 mg of CF per mg of cells for resting cells and 0.015 mg of CF per mg of cells for formate-fed cells), suggesting that depletion of energy stores affects transformation behavior. The observed finite transformation capacity, even with an exogenous energy source, suggests that toxicity was also a factor. CF transformation capacity was significantly lower than that for TCE, suggesting a greater toxicity from CF transformation. The toxicity of CF, TCE, and their transformation products to whole cells was evaluated by comparing the formate oxidation activity of acetylene-treated cells to that of non-acetylene treated cells with and without prior exposure to CF or TCE. Acetylene arrests the activity of methane monooxygenase in CF and TCE oxidation without halting cell activity toward formate. Significantly diminished formate oxidation by cells exposed to either CR or TCE without acetylene compared with that with acetylene suggests that the solvents themselves were not toxic under the experimental conditions but their transformation products were. The concurrent transformation of CF and TCE by resting cells was measured, and results were compared with predictions from a competitive-inhibition cometabolic transformation model. The reasonable fit between model predictions and experimental observations was supportive of model assumptions. PMID- 1905517 TI - Characterization of the nisin gene as part of a polycistronic operon in the chromosome of Lactococcus lactis ATCC 11454. AB - The location and organization of the nisin locus in Lactococcus lactis ATCC 11454 were studied. Primer extension of in vivo mRNA transcripts of the gene that encodes the nisin prepropeptide sequence indicated the presence of a promoter at least 4 kb upstream from the nisin gene and that the mRNA has several processing sites. Restriction fragment patterns using rare-cutting enzymes, orthogonal pulsed-field clamped homogeneous electric field (CHEF) agarose gel electrophoresis, and hybridization with nisin gene probes showed that the nisin prepropeptide gene was located on a megabase-size restriction fragment, which was taken as proof of a chromosomal location. This is contrary to earlier reports, which had indicated that genes for nisin production were located on plasmids. There was no evidence of more than one chromosomal location or more than one copy of the nisin gene. The restriction patterns indicated that the size of the L. lactis genome is about 2,500 kb. The previously observed (G. W. Buchman, S. Banerjee, and J. N. Hansen, J. Biol. Chem. 263: 16260-16266, 1988) downstream open reading frame (ORF) was fully sequenced to reveal an 851-amino-acid coding region, an upstream putative mRNA processing site, and a putative rho-independent terminator. The ORF was analyzed for secondary structural features, and the sequence data bases were searched for homologies. The ORF contained many amphipathic helices, a C-terminal transmembrane helix, and homologies to some membrane-associated proteins. It lacked an N-terminal membrane insertion sequence and accordingly appears to be associated with, and anchored to, the cytoplasmic side of the membrane. An additional ORF that possessed a ribosome-binding sequence and tandem promoters, indicating the beginning of a new operon, was identified still farther downstream. The results were consistent with the nisin gene being part of a polycistronic operon with a size greater than 8.5 kb. PMID- 1905518 TI - Improved electroporation and cloning vector system for gram-positive bacteria. AB - A protocol for transformation of intact Enterococcus faecalis cells by electroporation was developed through a systematic examination of the effects of changes in various parameters, including (i) growth conditions; (ii) composition of the electroporation solution; (iii) electroporation conditions, such as field strength and resistance; (iv) size, concentration, and purity of DNA used for transformation; and (v) conditions used to select for transformants. Key features of this protocol include the use of exponential-phase cells grown in inhibitory concentrations of glycine and the use of an acidic sucrose electroporation solution. Frequencies of greater than 2 x 10(5) transformants per microgram of plasmid DNA were obtained for E. faecalis cells, whereas various strains of streptococci and Bacillus anthracis were transformed at frequencies of 10(3) to 10(4) transformants per microgram of plasmid DNA with the same protocol. A novel Escherichia coli-Streptococcus and Enterococcus shuttle cloning vector, pDL276, was constructed for use in conjunction with the electroporation system. This vector features a multiple cloning site region flanked by E. coli transcription termination sequences, a relatively small size (less than 7 kb), and a kanamycin resistance determinant expressed in both gram-positive and gram-negative hosts. Various enterococcal and streptococcal DNA sequences were cloned in E. coli (including sequences that could not be cloned on other vectors) and were returned to the original host by electroporation. The vector and electroporation system was also used to clone directly into E. faecalis. PMID- 1905519 TI - Mold flora and aflatoxin contamination of stored and cooked samples of pearl millet in the Paharia tribal belt of Santhal paragana, Bihar, India. AB - Stored and cooked samples of pearl millet (Pennesetum typhoides), which is regularly consumed as food by the Paharia tribe in the hilly regions of Santhal Pargana, Bihar State, India, that were harvested in January 1989 were analyzed for mold flora, natural occurrence of Aspergillus flavus and A. parasiticus, and incidence and levels of aflatoxin B1. Of the 22 fungal species isolated, A. flavus and A. parasiticus were the predominant species (63.8%) during the rainy season, followed by other species of Aspergillus, Penicillium, Fusarium, Rhizopus, Helminthosporium, and Curvularia. Screening of 169 A. flavus and A. parasiticus strains showed that 59 of them were toxigenic, producing various combinations of aflatoxins B1, B2, G1, and G2. The amounts of aflatoxin B1 ranged between 4 and 30 mg/100 ml of liquid medium. Analysis of stored and cooked samples also revealed a high incidence and alarming levels of naturally produced aflatoxin B1. Forty-nine of 75 stored and 16 of 38 cooked samples contained various combinations of aflatoxins. The levels of aflatoxin B1 ranged between 17 and 2,110 ppb in stored samples and 18 and 549 ppb in cooked samples. The correlation of insect damage with A. flavus and A. parasiticus incidence and quantity of aflatoxin B1 was found to be insignificant. PMID- 1905521 TI - Toxicity and toxins of natural blooms and isolated strains of Microcystis spp. (Cyanobacteria) and improved procedure for purification of cultures. AB - All samples of cyanobacterial blooms collected from 1986 to 1989 from Lake Kasumigaura, Ibaraki Prefecture, Japan, were hepatotoxic. The 50% lethal doses (LD50s) of the blooms to mice ranged from 76 to 556 mg/kg of body weight. Sixty eight Microcystis cell clones (67 Microcystis aeruginosa and 1 M. viridis) were isolated from the blooms. Twenty-three strains (including the M. viridis strain) were toxic. However, the ratio of toxic to nontoxic strains among the blooms varied (6 to 86%). Microcystins were examined in six toxic strains. Five toxic strains produced microcystin-RR, -YR, and -LR, with RR being the dominant toxin in these strains. Another strain produced 7-desmethylmicrocystin-LR and an unknown microcystin. This strain showed the highest toxicity. Establishment of axenic strains from the Microcystis cells exhibiting extracellularly mucilaginous materials was successful by using a combination of the agar plate technique and two-step centrifugation. PMID- 1905520 TI - Sequencing and expression of the Butyrivibrio fibrisolvens xylB gene encoding a novel bifunctional protein with beta-D-xylosidase and alpha-L-arabinofuranosidase activities. AB - A single gene (xylB) encoding both beta-D-xylosidase (EC 3.2.1.37) and alpha-L arabinofuranosidase (EC 3.2.1.55) activities was identified and sequenced from the ruminal bacterium Butyrivibrio fibrisolvens. The xylB gene consists of a 1.551-bp open reading frame (ORF) encoding 517 amino acids. A subclone containing a 1.843-bp DNA fragment retained both enzymatic activities. Insertion of a 10-bp NotI linker into the EcoRV site within the central region of this ORF abolished both activities. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of cytoplasmic proteins from recombinant Escherichia coli confirmed the presence of a 60,000-molecular-weight protein in active subclones and the absence of this protein in subclones lacking activity. With p-nitrophenyl-beta-D-xylopyranoside and p-nitrophenyl-alpha-L-arabinofuranoside as substrates, the specific activity of arabinosidase was found to be approximately 1.6-fold higher than that of xylosidase. The deduced amino acid sequence of the xylB gene product did not exhibit a high degree of identity with other xylan-degrading enzymes or glycosidases. The xylB gene was located between two incomplete ORFs within the 4,200-bp region which was sequenced. No sequences resembling terminators were found within this region, and these three genes are proposed to be part of a single operon. Based on comparison with other glycosidases, a conserved region was identified in the carboxyl end of the translated xylB gene which is similar to that of glucoamylase from Aspergillus niger. PMID- 1905523 TI - Restriction enzyme analysis of Listeria monocytogenes strains associated with food-borne epidemics. AB - Listeria monocytogenes (serotype 4b) has caused four major food-borne epidemics in North America. In this study, L. monocytogenes isolates from the Nova Scotia (Canada), Boston (Mass.), and Los Angeles (Calif.) outbreaks were examined by restriction enzyme analysis with the endonuclease HhaI. Human isolates (n = 32) from the 1981 Canadian outbreak were compared with a strain recovered from coleslaw, which was epidemiologically incriminated as the vehicle of infection. After HhaI digestion, 29 of 32 isolates exhibited the restriction enzyme pattern of the reference coleslaw isolate. The restriction enzyme patterns of the nine clinical isolates from the 1983 Massachusetts outbreak were identical to each other but differed from those of raw milk isolates recovered from sources supplying the pasteurizer. Isolates (n = 48) from the 1985 California outbreak were evaluated. The restriction enzyme patterns of the L. monocytogenes isolates from humans and from the suspect cheese samples were identical to those of four of five cheese factory environmental isolates. Isolates from each of these outbreaks exhibited a restriction enzyme pattern that was characteristic of that outbreak. The case with which restriction enzyme analysis can be applied to all serotypes of L. monocytogenes argues for its use in the epidemiology of L. monocytogenes. PMID- 1905522 TI - Aerobic mineralization of vinyl chloride by a bacterium of the order Actinomycetales. AB - A gram-positive branched bacterium isolated from a trichloroethylene-degrading consortium mineralized vinyl chloride in growing cultures and cell suspensions. Greater than 67% of the [1,2-14C]vinyl chloride was mineralized to carbon dioxide, with approximately 10% of the radioactivity appearing in cell biomass and another 10% appearing in 14C-aqueous-phase products. PMID- 1905524 TI - Researching and evaluating model geriatric mental health programs, Part II: Measurement of outcomes. AB - The second article in this three-part series on researching and evaluating geriatric mental health programs focuses on measurement of outcomes. Five issues are discussed: (1) specifying relevant outcome variables, (2) reliability of measures, (3) systematic biases in assessment, (4) validity of measures, and (5) evaluation of program costs. PMID- 1905525 TI - [Malt digestive system lymphomas and alpha heavy chain diseases. Histological and immunohistochemical study. Apropos of 3 cases]. AB - Malt lymphomas are lymphomas developed from mucosa associated lymphoid tissue and may involve many sites such as the gastrointestinal tract, salivary glands, thyroid gland lung, breast and female genital tract. Histologically, their diagnosis is based upon the existence of four elements: centrocyte-like cells that are responsible for lymphoepithelial lesions that are sometimes very difficult to demonstrate reactive or residual follicles and plasma cells. We study 2 cases of gastric Malt lymphoma and one of alpha heavy chain disease involving the small intestine and the stomach and we try to define the common features of Malt lymphoma, alpha chain disease and non-secretary IPSID, which all present the clinical tetralogy mentioned above. PMID- 1905526 TI - [Lymphoma and Schistosoma mansoni schistosomiasis. Report of 1 case]. AB - A Burkitt's type of lymphocytic lymphoma associated with Schistosoma mansoni intestinal schistosomiasis was diagnosed in a 14 year old Zairian girl. The literature concerning this association is reviewed and discussed and various pathogenic hypotheses are proposed. PMID- 1905527 TI - Does patient education in rheumatoid arthritis have therapeutic potential? PMID- 1905528 TI - Heterotopic ossification and peripheral nerve entrapment: early diagnosis and excision. AB - Heterotopic ossification can occur in neurologic disorders, burns, musculoskeletal trauma, and metabolic disorders. In addition to producing the complications of contracture, skin breakdown, and pain, it can cause peripheral nerve entrapment. Nerve entrapment due to heterotopic ossification may be misdiagnosed, and it is difficult to evaluate and treat without recurrence. Computed tomography is especially useful in localization before surgical release of the entrapped nerve. Resection of heterotopic ossification can be successful using disodium etidronate to decrease the risk of recurrence, and resection can improve range of motion and nerve function. Two case studies of nerve entrapment due to heterotopic ossification are presented with the results of computed tomography localization, successful resection, and long-term follow-up. Clinicians should be aware of this complication and the potential for rapid nerve injury. If heterotopic ossification is causing clinically significant peripheral nerve entrapment, early surgical treatment may be indicated, and may be successful. PMID- 1905529 TI - Predictors of functional outcome and resource utilization in inpatient rehabilitation. AB - Consecutive patients (n = 1,289) discharged from two inpatient rehabilitation facilities were prospectively examined to determine the extent to which rehabilitative outcomes, functionally based progress, and associated resource utilization (in terms of rehabilitation length of stay) can be concomitantly predicted using the Tufts/New England Medical Center functional assessment tool and bivariate and multivariate statistical comparisons. A high percentage (greater than 50%) of statistically significant associations between the predictor variables and seven outcome measures were seen. The R2s corresponding to these associations were generally small and resistant to enhancement by commonly accepted statistical manipulations. Consequently, they are, in general, of limited predictive value for determining functional prognosis or resource utilization among rehabilitation inpatients. Although functionally based predictors appear to be the best predictors of functional progress, their effectiveness as predictors of other domains (eg, discharge outcome and rehabilitation length of stay) is variable. The implication is that a prospective payment system using such an array of predictors and directed primarily at cost containment is likely to overlook potentially important gains in functional progress and patient outcome. Furthermore, the functionally based predictors, taken individually, varied in effectiveness as predictors among facilities, and, taken collectively, they varied in effectiveness as predictors for different diagnostic groupings within a facility. The inconsistency of predictions according to the various domains appears to further limit their application to a prospective payment model. PMID- 1905530 TI - Comparative induction of cytochrome P450IVA1 and peroxisome proliferation by ciprofibrate in the rat and marmoset. AB - Chronic ciprofibrate administration resulted in distinct differences in hepatic responses between the two species examined. In the rat, hepatomegaly was observed with the coordinate induction of carnitine acetyltransferase, peroxisomal beta oxidation and cytochrome P450IVA1 activities. The latter induction of cytochrome P450IVA1-dependent fatty acid hydroxylase activity was specific to this cytochrome P450 sub family, as ciprofibrate pretreatment resulted in an inhibition of the enzyme activities associated with the cytochrome P450 IIB and IA sub-families. Induction of mitochondrial enzymes were also noted in the rat, but at a substantially lower level than the microsomal and peroxisomal enzyme changes noted above. The majority of these enzyme changes were reversible in the rat after a 4-week, inducer-free period. In contrast, the marmoset displayed a different pattern of enzyme changes in response to ciprofibrate and at the high dose level, inhibition of microsomal fatty acid hydroxylase activity was observed in addition to no change in carnitine acetyltransferase activity. Although peroxisomal beta-oxidation activity was induced in the marmoset, the specific activity was 10-fold lower than in the rat, concomitant with only minimum changes in the liver: body weight ratio. Taken collectively, our data have demonstrated that the marmoset is relatively refractory to ciprofibrate-induced liver enzyme changes with the implication that the extrapolation of the associated hepatotoxicity clearly documented in rodents must be viewed with extreme caution in non-human primates. PMID- 1905531 TI - Collagen cross-linking in bovine gingiva. AB - Tissue samples from 5 different sites of 6 bovine mandibles were used to quantify collagen cross-links as moles cross-link per mole of collagen. Gingiva contained primarily 3 reducible cross-links, deH-DHLNL, deH-HHMD, and deH-HLNL, and relatively small amounts of non-reducible cross-links. The cross-link density varied from site to site within the same mandible. DeH-DHLNL showed the most significant increase from anterior to posterior; the content in the retromolar region was 3-fold greater than in the anterior lingual site. Histologically, the posterior samples, especially the retromolar gingiva, contained less mature (thinner) collagen bundles. These findings suggest that the maturity of bovine mandibular gingival collagen varies at different sites. PMID- 1905532 TI - Inhibition of the growth of Streptococcus mutans, Streptococcus sobrinus and Lactobacillus casei by oral peroxidase systems in human saliva. AB - Streptococcus mutans, Strep. sobrinus and Lactobacillus casei were grown in glucose-supplemented, sterilized, human whole saliva, adjusted to pH 5, 6 or 7. Components of the antibacterial peroxidase system--hypothiocyanous acid (HOSCN) and hypothiocyanite ions (OSCN-)--were generated by adding exogenous H2O2 to sterilized saliva containing endogenous peroxidases and thiocyanate (SCN-) ions. HOSCN/OSCN- generation was proportional to the amount of H2O2 added, and more HOSCN/OSCN- was detected in saliva at pH 7 than at pH 5. However, the growth of mutans streptococci and L. casei was inhibited at pH 5 by HOSCN/OSCN-, whereas no inhibition was found at pH 7. The findings show that (a) sufficient amount of HOSCN/OSCN- will inhibit the growth of cariogenic bacteria in human saliva at pH 5; (b) this amount of HOSCN/OSCN- can be generated in saliva by exogenously added H2O2; and (c) peroxidase systems have stronger antistreptococcal effects in human whole saliva than in phosphate buffer. PMID- 1905533 TI - Hippocampal modulation of nucleus accumbens: behavioral evidence from amphetamine induced activity profiles. AB - The experiments examined amphetamine-induced locomotion and stereotyped behavior in hippocampal-ablated and control rats for 30 days following surgery. Locomotor counts, stereotypy ratings, and locomotor-time profiles showed that d-amphetamine sulfate produced a selective enhancement of locomotion (cage crosses) at the expense of stereotyped behavior in hippocampal rats relative to normal control rats. This enhancement emerged over the first 2 weeks postsurgery. To examine the role of the striatum in this amphetamine-induced effect, combined hippocampal damage and 6-hydroxydopamine-induced damage of the nucleus accumbens or caudate putamen were used. These results suggested that amphetamine-enhanced locomotion of hippocampal rats is dependent upon the integrity of the nucleus accumbens and may reflect a change of nucleus accumbens activity relative to caudate-putamen activity. Together these findings suggest that the hippocampus may participate in the control of locomotion by projections that modulate the activity of the nucleus accumbens. PMID- 1905534 TI - Arachidonic acid suppression of fatty acid synthase gene expression in cultured rat hepatocytes. AB - Rat hepatocytes were maintained in a serum-free, hormonally defined medium supplemented with 50-500 microM albumin-bound 20:1 (n-9) vs 20:4 (n-6). The induction of fatty acid synthase mRNA by a mix of insulin/dexamethasone/T3 was inhibited in a dose dependent fashion by 20:4 (n-6). The abundance of beta-actin mRNA was not suppressed by 20:4 (n-6). The expression of fatty acid synthase was actually stimulated 2-fold by 20:1 (n-9). It would appear that the in vivo inhibition of fatty acid synthase gene expression by dietary polyunsaturated fatty acids is a specific hepatocelluar event. PMID- 1905535 TI - Cell lineage-specific expression of the MIPP gene. AB - The expression of the mouse IAP promoted placental (MIPP) gene was examined in the tissues of the 13.5 day mouse conceptus by Northern hybridization analysis. MIPP transcripts were found in total cellular RNA isolated from the placenta, parietal yolk sac, and visceral yolk sac, but not the embryo or amnion. Expression in the visceral yolk sac was confined to the visceral endoderm cell layer suggesting that the MIPP gene is specifically expressed in tissues derived from the trophectoderm and primitive endoderm cell lineages. The expression of IAP genes paralleled that of MIPP in all tissues studied except for the presence of IAP transcripts in the amnion. PMID- 1905536 TI - Human placental sialidase complex: characterization of the 60 kDa protein that cross-reacts with anti-saposin antibodies. AB - Sialidase isolated from human placenta is associated with several proteins including acid beta-galactosidase, carboxypeptidase, N-acetyl-alpha galactosaminidase, and others. These proteins are thought to form an aggregated complex during isolation of sialidase. One of the proteins of 60 kDa was recently identified by Potier et al. (Biochem. Biophys. Res. Comm. 173, 449-456, 1990) as a sialidase protein: this protein also cross-reacted with anti-prosaposin antibodies. We have isolated this protein and from the following evidence identified it as a heavy chain component of immunoglobulin G and not sialidase or a derivative of prosaposin. On gel filtration HPLC, sialidase activity and the 60 kDa protein were clearly separated from one another. The 60 kDa protein cross reacted not only with antibodies raised against human saposins A, C, and D, but also with second antibody (goat anti-rabbit immunoglobulin G antibody) alone. This 60 kDa protein strongly cross-reacted with anti-human immunoglobulin G antibodies. The sequence of the initial 15 amino acids from the N-terminus of the 60 kDa protein was identical to the sequence of an immunoglobulin G heavy chain protein Tie (gamma 1). PMID- 1905537 TI - Nucleoside uptake in macrophages from various murine strains: a short-time and a two-step stimulation model. AB - Kinetics of [3H]-uridine uptake by murine peritoneal macrophages (pM phi) is early altered after exposure to a variety of stimuli. Alterations caused by Candida albicans, lipopolysaccharide (LPS) and recombinant interferon-gamma (rIFN gamma) were similar in SAVO, C57BL/6, C3H/HeN and C3H/HeJ mice, and were not correlated with an activation process as shown by the amount of tumor necrosis factor-alpha (TNF-alpha) being released. Short-time exposure to all stimuli resulted in an increased nucleoside uptake by SAVO pM phi, suggesting that the tumoricidal function of this cell either depends from the type of stimulus or the time when the specific interaction with the cell receptor is taking place. Experiments with priming and triggering signals confirmed the above findings, indicating that the increase or the decrease of nucleoside uptake into the cell depends essentially on the chemical nature of the priming stimulus. The triggering stimulus, on the other hand, is only able to amplify the primary response. PMID- 1905538 TI - Phosrestins I and II: arrestin homologs which undergo differential light-induced phosphorylation in the Drosophila photoreceptor in vivo. AB - The 49-kDa phosphoprotein gene and Dmarrestin gene encode two distinct arrestin homologs in the Drosophila photoreceptor. We find that two DNA fragments representing the Dmarrestin gene hybrid-selected a mRNA the in vitro translation of which produced a protein corresponding to the 39-kDa phosphoprotein previously reported by us. We propose to name these phosphorylated homologs of arrestin phosrestin I (49-kDa protein) and phosrestin II (39-kDa protein or the Dmarrestin gene product). We find that phosrestins I and II follow different time courses of phosphorylation in vivo; in the time period (approximate seconds) during which 43% of phosrestin I became phosphorylated, the phosphorylated state of phosrestin II remained unchanged from that of the nonilluminated flies. These results indicate that phosrestins I and II probably occupy different functional roles in the Drosophila photoreceptor. PMID- 1905539 TI - The smg GDS-induced activation of smg p21 is initiated by cyclic AMP-dependent protein kinase-catalyzed phosphorylation of smg p21. AB - We have shown that smg p21B is phosphorylated by cyclic AMP-dependent protein kinase (protein kinase A) and that membrane acidic phospholipids such as phosphatidic acid and phosphatidylinositol markedly inhibit the smg GDS-induced activation of smg p21B. However, we show here that phosphatidic acid and phosphatidylinositol exhibit a less inhibitory effect on the smg GDS-induced activation of the phosphorylated form of smg p21B. Thus, in the presence of membrane acidic phospholipids, the smg GDS-induced activation of smg p21B is totally dependent on the protein kinase A-catalyzed phosphorylation of smg p21B. Since smg p21B is located on the membranes in resting cells, it is likely that the smg GDS-induced activation of smg p21B is initiated by the protein kinase A activation. PMID- 1905540 TI - Identification of amino acid substitutions in the lipopeptide surfactin using 2D NMR spectroscopy. AB - It is generally accepted that surfactin, being produced by various Bacillus subtilis strains, is a cyclic lipopeptide built from the heptapeptide L-Glu-L-Leu D-Leu-L-Val-L-Asp-D-Leu-L-Leu and a beta-hydroxy fatty acid with variable chain length of 13 - 15 carbon atoms. We investigated surfactin from Bacillus subtilis ATCC 21332 and OKB 105, dissolved in pyridine and methanol, with two-dimensional H NMR spectroscopy. In the NH-fingerprint region, 21 well resolved cross peaks are observed instead of the expected seven cross peaks for the given heptapeptide. We were able to assign all proton signals to 21 amino acids, to identify three heptapeptides, and thus to prove the existence of structural analogues of surfactin. In the major fraction A, the peptide sequence is as given above. In fractions B and C, the C-terminal leucine is replaced by valine and isoleucine, respectively. PMID- 1905541 TI - On the structure of human autoantibodies. PMID- 1905543 TI - Prognostic significance of acute epilepsia partialis continua. AB - We present 3 patients in whom epilepsia partialis continua was the presenting sign of an acute, rapidly evolving and catastrophic neurologic illness. Initial seizures were partial simple (i.e., eye deviation in one, finger twitching in one) which progressed to multifocal partial seizures. The course of the epilepsia partialis continua was 36-41 days. Prognosis was uniformly poor (i.e., death in 2, vegetative state in 1); therefore, epilepsia partialis continua in the context of an acute neurologic illness may herald a grim outcome. PMID- 1905542 TI - Epidemiology of absence epilepsy: EEG findings and their predictive value. AB - This population-based study of absence epilepsy comprised 97 children, ranging in age from newborns to 15 years. All had regular bilaterally synchronous and symmetric 2-4 Hz spike-and-slow wave discharges and absences with or without generalized tonic-clonic seizures (GTCS). Patients without GTCS tended to have long episodes of 2-4 Hz spike-and-slow wave discharges (greater than or equal to 10 sec), and simultaneous clinical correlates more frequently than those with GTCS. Posterior delta rhythm was found only in patients without GTCS. Focal abnormalities, albeit transient, were more frequent among patients with GTCS. The initial electroencephalogram was of some early predictive value in patients with only absences at the time of the initial registration. Brief episodes of 2-4 Hz spike-and-slow wave (less than 10 sec) without clinical correlates were associated with a slightly increased risk of future GTCS. PMID- 1905544 TI - Teaching correct and safe bedside procedures. PMID- 1905546 TI - Organic osmolytes in methanogenic archaebacteria. AB - Methanogenic archaebacteria have developed unique ways of dealing with osmotic stress. While several of them have transport systems capable of internalizing betaine, an osmolyte in many eubacteria, in general they have developed de novo synthesis of a novel series of beta-amino acids as compatible solutes. 13C-NMR spectroscopy has been the key tool in elucidating both the identity of these organic osmolytes and in investigating their dynamics. PMID- 1905545 TI - National policy perspectives. The Prospective Payment Assessment Commission: responsibilities and recent findings. PMID- 1905547 TI - Structural characteristics of methanogenic cofactors in the non-methanogenic archaebacterium Archaeoglobus fulgidus. AB - Archaeoglobus fulgidus is an extremely thermophilic, sulphate reducing archaebacterium thought to represent a biochemical missing-link between sulphur metabolizing bacteria and methanogenic bacteria. Whereas the phylogenetic position of A.fulgidus is closer to the sulphur-metabolizing bacteria, there is a partial overlap in the biochemical machinery of A.fulgidus with both groups of bacteria. In particular, the presence of a number of aberrant cofactors up to now thought to be involved exclusively in the process of methanogenesis in methanogenic archaebacteria, i.e. coenzyme F420, methanofuran and methanopterin, has been indicated by previous studies. Here we present evidence for the structural identity of the methanopterin cofactor of A.fulgidus with the methanopterin isolated from Methanobacterium thermoautotrophicum and show that this non-methanogenic bacterium contains two as yet unknown analogues of coenzyme F420. The levels of the various cofactors were determined in cultures grown either on formate or lactate as the carbon source and sulphate or thiosulphate as the sulphur source. PMID- 1905548 TI - Queuine metabolism and cadmium toxicity in Drosophila melanogaster. AB - Queuine can replace guanine in the anticodon of certain tRNAs and is a hypermodified guanine derivative that can be synthesized by bacteria but not by mice. The study demonstrates that Drosophila can incorporate dietary queuine into tRNA but cannot synthesize it de novo for this purpose. Since an earlier study had shown that dietary CdCl2 caused Drosophila to increase greatly the proportion of queuine-containing tRNA over non-queuine tRNA the ability of dietary queuine to counteract cadmium toxicity was evaluated. When queuine was present in the cadmium-containing medium more pupae matured into adults than when queuine was absent. Other studies had demonstrated that the transglycosylase enzyme, that catalyzes the replacement of guanine in the anticodon of tRNA by queuine, is present in Drosophila larvae but the tRNA is virtually devoid of queuine. This study shows that in the presence of dietary queuine the larval tRNA contains abundant amounts of queuine. Therefore, we postulate a significant role for bacteria in supplying queuine to Drosophila for its incorporation into tRNA and that the control of this process by Drosophila is passive, i.e. is not an essential feature in differentiation. PMID- 1905549 TI - Diagnostic usefulness of cerebrospinal fluid in multiple sclerosis. AB - Multiple sclerosis (MS) is one of the most common demyelinating diseases of the central nervous system affecting adults between the ages of 20 and 40 years. Clinically, it is characterized by episodes of exacerbations and remissions. Although the cause of MS is unknown, it is generally believed that one or more infectious agents triggers an autoimmune response that causes myelin destruction. There is no known cure for this disease; however, early diagnosis is helpful in the management of patients with MS. The diagnosis of MS is commonly made on the basis of established clinical criteria. No specific laboratory diagnostic test exists, but detection of abnormalities in cerebrospinal fluid (CSF) is a useful aid to support the clinical diagnosis of MS. This review describes the most common CSF abnormalities. These include (a) elevation of immunoglobulin G (IgG), IgG index and IgG synthesis rate; and (b) detection of oligoclonal IgG bands in the CSF by electrophoresis and isoelectric-focusing procedures. PMID- 1905550 TI - Effects of monoclonal antibodies on tissue-type plasminogen activator (t-PA) binding to lysine, fibrin and heparin and on fibrin-mediated enhancement of one chain t-PA amidolytic activity. AB - The effects of 4 monoclonal antibodies against human tissue-type plasminogen activator (t-PA) on binding of t-PA to lysine, fibrin, and heparin, and on fibrin mediated activation of one-chain t-PA-amidolytic activity were investigated. The association constants of the antibodies were determined in a direct assay to be equal to 0.125 l/nmol, 0.225 l/nmol, 0.4 l/nmol, and 0.5 l/nmol for mAB 5, mAB 16, mAB 25, and mAB 31, respectively. All 4 monoclonal antibodies inhibited binding of intact t-PA to lysine-Sepharose and fibrin, and they suppressed fibrin mediated activation of one-chain t-PA-amidolytic activity. Binding analysis demonstrated that mAB 25 inhibited t-PA binding to lysine-Sepharose and to fibrin as well as fibrin-mediated enhancement of one-chain t-PA-amidolytic activity in a competitive manner with inhibitor constants of 5 nmol/l, 3 nmol/l and 10 nmol/l, respectively. It was also shown that free lysine counteracts the association of t PA with the antibodies. Binding of t-PA to heparin is only moderately affected by the 4 antibodies. Since t-PA possesses two homologous kringle domains which contain fibrin (lysine) binding sites, the results underline the importance of a lysine binding site for fibrin binding by intact t-PA and show that the binding of the enzyme to fibrin and lysine is mediated by the same binding site of a kringle domain. The parallel effects of antibodies on fibrin binding and on fibrin-mediated enhancement of one-chain t-PA amidolytic activity proves that the site of fibrin binding is identical with the site of fibrin activation. The binding site of heparin apparently differs from lysine and fibrin binding sites. PMID- 1905551 TI - Global minimum energy conformations of thyrotropin releasing hormone analogs by simulated annealing. II. AB - Lowest conformational energy structures of seventeen thyrotropin releasing hormone analogs have been studied by simulated annealing. A surprising conformational similarity was observed for the peptide backbone. The possible role of each substituent in its biological activity is inferred. A composite hydrogen-bonding environment is proposed for the TRH with respect to receptor binding. PMID- 1905552 TI - Transient elevation of serum HIV antigen levels associated with intercurrent infection. PMID- 1905554 TI - Presence of HIV antigen p24 in the synovial fluid of a patient without antigenemia suffering from staphylococcal arthritis. PMID- 1905553 TI - Prevalence of HIV-1 p24 antigenemia in African and North American populations and correlation with clinical status. AB - Sera from 622 individuals and culture supernatants from three HIV-1 viral isolates were assayed for HIV-1 p24 antigen to investigate the frequency of p24 antigenemia in African and North American populations using three commercial HIV 1 p24 antigen assays (Coulter, Du Pont, and Abbott). The prevalence of p24 antigenemia in 89 hospitalized Zairian AIDS patients was significantly lower than in 47 clinically comparable AIDS patients in the USA (17 versus 48%, P less than 0.0001). Prevalence of p24 antigenemia in sera from 200 asymptomatic HIV-1 infected individuals was also lower in individuals from Zaire compared with 83 individuals in the USA (3.5 versus 7%). In African individuals, antigenemia prevalence increased with advanced clinical status: 8% in ambulatory AIDS patients, 17% in hospitalized AIDS patients and 18% in postmortem AIDS patients. Acid hydrolysis treatment of sera from 63 Zairian AIDS patients initially negative for p24 antigen showed an 11% positivity rate confirmed by neutralization, suggesting that immune complexing of p24 antigen may play a role in the observed lower p24 antigenemia rates reported for African individuals. PMID- 1905556 TI - Compensatory increase in lactase expression by enterocytes of neonatal pigs on a low energy intake. AB - A restricted energy intake in the immediate postnatal period has been found to result in a significant increase in the maximal expression of lactase by enterocytes from 2-week-old pigs. Although villus size was significantly reduced on a low compared with a high food intake, total villus lactase activity was unaffected because of the compensatory increase in lactase expression by individual enterocytes. PMID- 1905555 TI - Controlling HIV in Africa: effectiveness and cost of an intervention in a high frequency STD transmitter core group. AB - Since 1985, a population of over 1,000 predominantly HIV-positive female prostitutes residing in a low-income area of Nairobi, has been enrolled in a sexually transmitted disease (STD)/HIV control programme. The major elements of the programme include the diagnosis and treatment of conventional STD, and the promotion of condom use to prevent the transmission of HIV and other sexually transmitted infections. Using estimates of numbers of HIV-seropositive prostitutes, numbers of sexual contacts, susceptibility of clients to HIV, HIV transmission efficiency, rates of condom use and the basic reproductive rate of HIV infection in Kenya, we estimate that the programme is responsible for preventing between 6,000 and 10,000 new cases of HIV infection per year among clients and contacts of clients. The total annual operating cost of the programme is approximately US$77,000 or between US$8.00 and US$12.00 for each case of HIV infection prevented. Programmes to reduce the transmission of HIV and other sexually transmitted infections which are targeted at high-frequency STD transmitters, such as prostitutes, can be effective and relatively inexpensive to undertake. More such programmes should be developed and evaluated in different settings. PMID- 1905557 TI - Comparison of a single-injection technique and inulin clearance for determining glomerular filtration rate in the sheep. AB - Glomerular filtration rate (GFR) was assessed over a 2 h period by the clearance of inulin (Cin) and in the subsequent 2 h period by a single-injection technique using radiolabelled sodium iothalamate (Ciot) or chromium-EDTA (CEDTA). Regression analysis yielded a significant correlation (P less than 0.05) between the standard clearance technique and the single-injection method, with the relationship Ciot = -10.67 + 1.25Cin with a significant correlation coefficient of r = 0.71 (P less than 0.02). There was better agreement between clearance values of inulin measured on successive days than between values determined by the single-injection technique on successive days. Cin remains the method of choice in sheep. PMID- 1905559 TI - Long-term storage of concentrated tris-borate-EDTA electrophoresis buffers without precipitation. PMID- 1905558 TI - Gene deletions in the human immunoglobulin heavy chain constant region locus: molecular and immunological analysis. AB - Single and extensive multigene deletions have been described in the Ig CH immunoglobulin heavy-chain constant region genes, some of these encompassing up to 160 kilobases. To date six different multigene deletion haplotypes have been identified, designated I to VI according to the chronological order of their findings; deletion I (del G1-EP1-A1-GP-G2-G4), II (del EP1-A1-GP), III (del A1-GP G2-G4-E), IV (del EP1-A1-GP-G2-G4), V (del GP-G2-G4-E-A2), VI (del G1-EP1-A1-GP G2). Individuals were found either homozygous for one type of deletion or heterozygous for two different deletions, mainly in the Mediterranean area. The high level of consanguinity in the Tunisian population accounts for the high frequency of individuals homozygous for one or the other of these multigene deletions which involve highly homologous regions as hot spots of recombinations, outside of the switch sequences, in the Ig CH locus. In 15 cases out of 16, these multigene deletions have been observed in healthy people, although these individuals lacked several immunoglobulin subclasses and, even, one class. Such an immunological situation makes it possible to study the importance of these subclasses for the overall immunity, and to analyse the specific immune responses by the retained IgG and IgA subclasses. PMID- 1905561 TI - Fate of exogenous and endogenous prostaglandins D2 and E2 in the perfused rat liver. AB - The degradation of radiolabelled exogenous PGD2 and PGE2 was compared to that of endogenous labelled prostaglandins synthesized after stimulation with PMA in the perfused rat liver. With exogenous PGD2 and PGE2 the same degradation products were found in the perfused liver as in hepatocyte primary cultures. The major metabolite of PGD2 was dinor-PGD2 while tetranor-PGE1 was the main degradation product of PGE2. Some polar metabolites and tritiated water were also formed. The metabolites detected with endogenous prostaglandins were similar to those obtained with exogenous PGD2. Over 99% of the labelled prostaglandins were degraded in the recirculating perfusion within 40 min. In the open perfusion system, 95% of endogenous PGD2 was calculated to be degraded after a single passage through the liver, which suggests that hepatocytes play an important role in the removal of biologically active prostaglandins. PMID- 1905560 TI - Measurement of prostaglandin G/H synthase and lipoxygenase activity in the stomach wall by HPLC. AB - A method for the determination of prostaglandin G/H synthase and lipoxygenase activities in tissues was developed and employed with rat gastric mucosa samples. Tissues and microsomes were incubated in a buffer containing nonionic detergent and 1.32 mM arachidonic acid for 10 min. Following extraction with ethyl acetate, the oxidation products of arachidonic acid were derivatized with panacyl bromide. A reversed-phase column and a quaternary mobile phase were used to separate and quantitate the panacyl bromide esters of prostaglandin E2 and leukotriene C4/D4. Prostaglandin G/H synthase and lipoxygenase activities were determined in gastric mucosa and were 371 +/- 66 and 173 +/- pg/mg/min, respectively. PMID- 1905562 TI - Formation of ketodienoic fatty acids by the pure pea lipoxygenase-1. AB - A pure lipoxygenase from dried green pea seeds (isoenzyme 1) oxygenates linoleic acid to 9(S/R)-hydroperoxy-10E,12Z-octadecadienoic acid (9-HPODE) and 13(S/R) hydroperoxy-9Z,11E-octadecadienoic acid (13-HPODE). Furthermore (10E,12Z)-9-keto 10,12-octadecadienoic acid (9-KODE) and (9Z,11E)-13-keto-9,11-octadecadienoic acid (13-KODE) in a ratio of 1:1 were formed. Uv-spectroscopic measurements and HPLC data indicated a hydroperoxy fatty acid: keto fatty acid ratio of about 2:1. The product mixture formed from arachidonic acid was even more complex. 15-, 11-, 9- and 5-H(P)ETE1 and their corresponding keto derivatives have been detected. The chemical structures of the compounds have been identified by HPLC analysis, by uv- and ir-spectroscopy and gas chromatography/mass spectrometry of the native compounds and their hydrogenated derivatives. The data presented indicate that a pure lipoxygenase catalyzes the formation of both hydroperoxypolyenoic fatty acids and ketopolyenoic fatty acids from linoleic acid and arachidonic acid. The possible mechanism of the formation of the keto compounds is discussed. PMID- 1905563 TI - The construction of a monoclonal diagnostic system for the field detection of Vibrio cholerae. AB - An enzyme-based double monoclonal field diagnostic system detecting both serotypes of Vibrio cholerae has been developed. The system uses nitrocellulose as a solid support, 1.25% skimmed dried milk as blocking reagent, water as washing reagent, and alkaline phosphatase cross-linked to antibody by means of glutaraldehyde as detecting reagent. The sensitivity of the system was 10(5) vibrios/ml. The biotin-avidin system gave sensitivity an order of magnitude weaker. There were no cross-reactions with the range of other bacteria tested. PMID- 1905564 TI - [Severe otitis externa in a child. Apropos of a case]. PMID- 1905566 TI - Murine erythroid cell lines derived with c-myc retroviruses respond to leukemia inhibitory factor, erythropoietin, and interleukin 3. AB - The transforming potential of the c-myc gene is shown here, for the first time, to include murine erythroid cells. Continuously growing cell lines were reproducibly generated by infection of day 13 CBA fetal liver cells with novel recombinant c-myc retroviruses. By cytostaining, most cells resembled early erythroblasts, but certain lines also contained significant numbers of hemoglobinized cells. RNA analysis revealed substantial expression of the genes encoding beta-globin and the erythroid-specific transcription factor GF-1. Although apparently immortal, the lines were not initially transplantable. Thus, constitutive myc expression in early erythroid cells can enhance their self renewal capacity but is insufficient to fully transform them. The cell lines proliferated without the addition of exogenous factors, but their clonogenicity in semisolid medium was enhanced in the presence of erythropoietin, interleukin 3, and/or leukemia-inhibitory factor. In combination with either interleukin 3 or erythropoietin, leukemia-inhibitory factor also facilitated differentiation of certain lines. These results suggest that leukemia-inhibitory factor may have a previously unsuspected role in the regulation of erythropoiesis and could be considered as a possible therapeutic agent for the clinical management of erythroleukemia. PMID- 1905565 TI - Ischemic induction of protooncogene expression in gerbil brain. AB - Cerebral ischemia and reperfusion results in an active series of metabolic events, eventually leading to cell death. The expression of specific genes during cerebral ischemia and reperfusion may play an important, determinant role in the mechanisms controlling cellular processes. Ten minutes of bilateral carotid occlusion in the Mongolian gerbil was found to increase the messenger RNA for both the c-fos and c-jun protooncogenes. The changes in gene expression were detected in the regions of ischemia, specifically the cortex and striatum, and no increases were seen in either the brain stem or the cerebellum, which possess a separate circulation. Induction of protooncogene mRNA is correlated to the duration of ischemia, i.e., the longer the time of ischemia, the greater the increase in c-fos expression. Pretreatment of animals with pentobarbital reduced the effect of the ischemic insult and prevented the increase in c-fos mRNA. Analysis of the c-fos and c-jun proteins after ischemia demonstrated an increase in the formation of a functional transcriptional complex and association with the AP-1 binding region. These findings suggest that ischemic cell death and recovery in neurodegenerative disorders such as stroke may involve the regulated expression of these protooncogenes early in the pathway of ischemia. PMID- 1905567 TI - Electron microscopic localization of acridine orange binding to euchromatin in human neuroblastoma cells. AB - The purpose of the present study was to examine the distribution pattern of acridine orange (AO) chromatin interaction products (AOCI) in human neuroblastoma IMR-32 cells and to test whether AO labeling is correlated with BrdU incorporation, and immunohistochemical localization of DNA polymerase alpha, and human N-myc-gene product. Effects of aphidicolin, alpha-amanitin, and actinomycin D on visualization of AO binding to euchromatin and on N-myc-gene expression were also examined. About 25% of the cell nuclei in logarithmic growth phase were immunohistochemically demonstrated to be labeled with BrdU after incubation at 37 degrees for 30 min, indicating cells in DNA synthesis. Most of the cell nuclei showed positive immunoreactivity to DNA polymerase alpha, while human N-myc gene product was found in about 60-80% of the cell nuclei. Electron microscopic studies revealed that about 25% of neuroblastoma cells showed characteristic AOCI within cell nuclei. In the presence of aphidicolin, alpha-amanitin, and actinomycin D, positive cells for N-myc gene product decreased markedly. Percentages of AO positive cells and numbers of AOCI per cell nucleus also showed a marked decrease. But northern blot analysis demonstrated that the expression level of N-myc gene was only repressed by the transcriptional inhibitors alpha amanitin and actinomycin D. However, no repression was caused by aphidicolin. The present and previous studies of the authors suggest that the ultracytochemical AO method may be indicative for conformational changes of chromatin of cells confined to the cell cycle. Inhibitors of RNA and DNA synthesis then may change the conformational state of chromatin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1905568 TI - [Normal rabbit sera. An immunologic and immunohistologic study]. AB - Reported in this paper are results obtained from immunological and immunohistochemical studies into non-immune rabbit sera which were tested for various antimycobacterial antibodies. 11% of the sera were found to be positive by transmigration electrophoresis, while antibodies against mycobacteria were recorded from 94% of all rabbits by peroxidase-antiperoxidase (PAP), an immunohistological technique of higher sensitivity. Several owners had kept rabbits together with fowl, which was considered to be one of the causes of very high contamination of rabbit stock with mycobacterial antigens. Antimycobacterial antisera and control sera should be obtained from animals with no record of natural immunisation against mycobacteria, since this is the only way to avoid falsely positive reactions, primarily to the use of the immunohistological PAP technique. PMID- 1905569 TI - Rapid activation of phosphatidate phosphohydrolase in mesangial cells by lipid A. AB - Knowledge of rapid events in cell signaling initiated by lipid A, the core moiety of bacterial lipopolysaccharide, is limited. In the present study we have demonstrated that cis-parinaric acid (cis-PnA) rapidly labels 1,2-sn diacylglycerol (DAG) subsequent to labeling of phosphatidic acid (PA). Stimulation of microsomal membranes with lipid A decreased the level of PA labeled with cis-PnA within 5 s and increased the proportion of fluorescent label in DAG. Lipid A stimulation of DAG synthesis at 5-15 s was inhibited by incubation of mesangial cells with pertussis toxin prior to isolation of microsomal membranes. Inhibition of DAG formation was accompanied by an accumulation of the mass and fluorescent label in the cis-PnA-labeled phosphatidic acid pool. GTP gamma S caused a decrease in labeled PA and an increase in labeled 1,2-DAG. We conclude that the PA pool was enlarged via the lipid A sensitive lyso-PA acyl transferase (lyso-PA-AT) and was decreased by a phosphatidate phosphohydrolase to form DAG. The phosphatidate phosphohydrolase was at least partly regulated by a pertussis-sensitive G-protein. Lipid A or 1,2 dilinoleyl-PA, a product of lyso-PA-AT, induced cell activation as monitored by actin reorganization and cellular shape changes. Pretreatment of cells with pertussis toxin prevented the morphological changes normally induced by lipid A or 1,2-dilinoleyl-PA. In contrast, 1-oleoyl-2-acetylglycerol induced rapid actin reorganization and shape change, presumably bypassing the pertussis blockade. We propose that specific pools of PA and PA-derived DAG are key elements in rapid signaling in mesangial cells and are independent of the PI cycle and phospholipase C. PMID- 1905570 TI - Distal pocket polarity in ligand binding to myoglobin: structural and functional characterization of a threonine68(E11) mutant. AB - Site-directed mutagenesis studies have confirmed that the distal histidine in myoglobin stabilizes bound O2 by hydrogen bonding and have suggested that it is the polar character of the imidazole side chain rather than its size that limits the rate of ligand entry into the protein. We constructed an isosteric Val68 to Thr replacement in pig myoglobin (i) to investigate whether the O2 affinity could be increased by the introduction of a second hydrogen-bonding group into the distal heme pocket and (ii) to examine the influence of polarity on the ligand binding rates more rigorously. The 1.9-A crystal structure of Thr68 aquometmyoglobin confirms that the mutant and wild-type proteins are essentially isostructural and reveals that the beta-OH group of Thr68 is in a position to form hydrogen-bonding interactions both with the coordinated water molecule and with the main chain greater than C=O of residue 64. The rate of azide binding to the ferric form of the Thr68 mutant was 60-fold lower than that for the wild-type protein, consistent with the proposed stabilization of the coordinated water molecule. However, bound O2 is destabilized in the ferrous form of the mutant protein. The observed 17-fold lowering of the O2 affinity may be a consequence of the hydrogen-bonding interaction made between the Thr68 beta-OH group and the carbonyl oxygen of residue 64. Overall association rate constants for O2, NO, and alkyl isocyanide binding to ferrous pig myoglobin were 3-10-fold lower for the mutant compared to the wild-type protein, whereas that for CO binding was little affected.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1905571 TI - Dihydrofolate reductase: sequential resonance assignments using 2D and 3D NMR and secondary structure determination in solution. AB - Three-dimensional (3D) heteronuclear NMR techniques have been used to make sequential 1H and 15N resonance assignments for most of the residues of Lactobacillus casei dihydrofolate reductase (DHFR), a monomeric protein of molecular mass 18,300 Da. A uniformly 15N-labeled sample of the protein was prepared and its complex with methotrexate (MTX) studied by 3D 15N/1H nuclear Overhauser-heteronuclear multiple quantum coherence (NOESY-HMQC), Hartmann-Hahn heteronuclear multiple quantum coherence (HOHAHA-HMQC), and HMQC-NOESY-HMQC experiments. These experiments overcame most of the spectral overlap problems caused by chemical shift degeneracies in 2D spectra and allowed the 1H-1H through space and through-bond connectivities to be identified unambiguously, leading to the resonance assignments. The novel HMQC-NOESY-HMQC experiment allows NOE cross peaks to be detected between NH protons even when their 1H chemical shifts are degenerate as long as the amide 15N chemical shifts are nondegenerate. The 3D experiments, in combination with conventional 2D NOESY, COSY, and HOHAHA experiments on unlabelled and selectively deuterated DHFR, provide backbone assignments for 146 of the 162 residues and side-chain assignments for 104 residues of the protein. Data from the NOE-based experiments and identification of the slowly exchanging amide protons provide detailed information about the secondary structure of the binary complex of the protein with methotrexate. Sequential NHi-NHi+1 NOEs define four regions with helical structure. Two of these regions, residues 44-49 and 79-89, correspond to within one amino acid to helices C and E in the crystal structure of the DHFR.methotrexate.NADPH complex [Bolin et al. (1982) J. Biol. Chem. 257, 13650-13662], while the NMR-determined helix formed by residues 26-35 is about one turn shorter at the N-terminus than helix B in the crystal structure, which spans residues 23-34. Similarly, the NMR determined helical region comprising residues 102-110 is somewhat offset from the crystal structure's helix F, which encompasses residues 97-107. Regions of beta sheet structure were characterized in the binary complex by strong alpha CHi NHi+1 NOEs and by slowly exchanging amide protons. In addition, several long range NOEs were identified linking together these stretches to form a beta-sheet. These elements align perfectly with corresponding elements in the crystal structure of the DHFR.methotrexate.NADPH complex, which contains an eight stranded beta-sheet, indicating that the main body of the beta-sheet is preserved in the binary complex in solution. PMID- 1905572 TI - Purification and reconstitution of the high affinity choline transporter. AB - The high-affinity choline transporter has been solubilized from synaptosomal membranes by various detergents. The solubilized carrier protein has been incorporated into liposomes after removal of the detergent by dialysis. Using the reconstitution of choline transport activity as an assay, the components catalyzing choline translocation were purified from the detergent extract by ion exchange chromatography on a Mono-Q column followed by immunoaffinity chromatography. Monitoring the active fractions by sodium dodecylsulfate polyacrylamide gel electrophoresis and isoelectrofocussing gave one major protein with an apparent molecular weight of about 90,000 and an isoelectric point of pH 4.7. The isolated protein appeared to be heavily glycosylated as shown by lectin binding; upon treatment with endoglycosidase F the polypeptide was degraded to an apparent molecular weight of about 65,000. Accumulation of choline into liposomes reconstituted with the purified protein was driven by artificially imposed sodium gradients and inhibited by hemicholinium-3. PMID- 1905573 TI - Hydrophobic membrane thickness and lipid-protein interactions of the leucine transport system of Lactococcus lactis. AB - The effect of the phospholipid acyl chain carbon number on the activity of the branched-chain amino acid transport system of Lactococcus lactis has been investigated. Major fatty acids identified in a total lipid extract of L. lactis membranes are palmitic acid (16:0), oleic acid (18:1) and the cyclopropane-ring containing lactobacillic acid (19 delta). L. lactis membrane vesicles were fused with liposomes prepared from equimolar mixtures of synthetic phosphatidylethanolamine (PE) and phosphatidylcholine (PC) with cis mono unsaturated acyl chains. The activity of the branched-chain amino acid carrier is determined by the bulk properties of the membrane (Driessen, A.J.M., Zheng, T., In 't Veld, G., Op den Kamp, J.A.F. and Konings, W.N. (1988) Biochemistry 27, 865 872). PE acts as an activator and PC is ineffective. Counterflow and protonmotive force driven transport of leucine is sensitive to changes in the acyl chain carbon number of both phospholipids and maximal with dioleoyl-PE/dioleoyl-PC. Above the gel to liquid-crystalline phase transition temperature of the lipid species, membrane fluidity decreased with increasing acyl chain carbon number. Our data suggest that the carbon number of the acyl chains of PE and PC determine to a large extent the activity of the transport system. This might be relevant for the interaction of PE with the transport protein. Variations in the acyl chain composition of PC exert a more general effect on transport activity. The acyl chain composition of phospholipids determines the membrane thickness (Lewis, B.A. and Engelman, D.M. (1983) J. Mol. Biol. 166, 211-217). We therefore propose that the degree of matching between the lipid-bilayer and the hydrophobic thickness of the branched-chain amino acid carrier is an important parameter in lipid-protein interactions. PMID- 1905574 TI - The expression and localization of urokinase-type plasminogen activator and its type 1 inhibitor are regulated by retinoic acid and fibroblast growth factor in human teratocarcinoma cells. AB - Human Tera 2 embryonal carcinoma cells switch gradually from rapidly growing undifferentiated cells to almost nonproliferating cells during retinoic acid (RA) induced neuronal differentiation. This process is associated with the increased expression of type 1 plasminogen activator inhibitor (PAI 1) mRNA, and the secreted inhibitor is immobilized to the pericellular area. Furthermore, the differentiation is accompanied by a decrease in the amount of both the secreted tissue-type PA (tPA) and the mainly cell-associated urokinase-type PA (uPA) activity. In RA-differentiated cells, uPA becomes localized at the vinculin-rich cell-substratum adhesion sites. Fibroblast growth factor activity has been associated with various events during embryonal growth and with the regulation of proteolytic enzymes. A short-term treatment of the undifferentiated Tera 2 cells with basic fibroblast growth factor (bFGF) increases uPA mRNA levels and the cell associated uPA activity, whereas the secretory tPA activity decreases. bFGF induces PAI 1 mRNA expression in the undifferentiated cells, but unlike PAI 1 protein after RA-treatment, the inhibitor does not accumulate around the cells but is released in the medium. A similar exposure to bFGF has less effect on the RA-differentiated Tera 2 cells. Under these conditions bFGF treatment leads to an increase in the amounts of PAI 1 and uPA mRNAs, but no changes in the localization of these components can be seen. Differentiation of human embryonal carcinoma cells is thus connected with an altered response to bFGF. PMID- 1905575 TI - Pharmacokinetic studies of the nitroglycerin metabolites, 1,2- and 1,3- glyceryl dinitrates, in the rat. AB - 1,2- and 1,3-glyceryl dinitrates (1,2-GDN and 1,3-GDN) are the primary metabolites of glyceryl trinitrate, a commonly used anti-anginal agent. The goal of this study was to examine the pharmacokinetic properties of these metabolites in rats. Sprague-Dawley rats were infused intravenously with 0.25 or 2.0 micrograms min-1 of either 1,2- or 1,3-GDN for 70 min, during which steady state blood concentrations were achieved. Post-infusion blood samples were collected for 30 min. 1,2-GDN was found to possess slightly higher clearance (32.3 vs 20.8 ml min-1 kg-1) and volume of distribution (695 vs 454 ml kg-1) than 1,3-GDN; however, the two metabolites exhibited similar mean residence times (22.0 vs 21.8 min). Upon an 8-fold increase in the infusion rate, the pharmacokinetic parameters were not significantly altered for either 1,2- or 1,3-GDN. When each GDN was co-infused with an 8-fold higher dose of the other GDN, there were also no significant changes in the parameters. PMID- 1905576 TI - Supersensitivity to the reinforcing effects of cocaine following 6 hydroxydopamine lesions to the medial prefrontal cortex in rats. AB - The effects of neurotoxic lesions to the medial prefrontal cortex on both the acquisition and maintenance of intravenous cocaine self-administration were examined. In one experiment, acquisition of intravenous cocaine self administration (0.25, 0.5 or 1.0 mg/kg/infusion) was measured in separate groups of rats 14 days following either a sham or 6-hydroxydopamine lesion to the medial prefrontal cortex. For sham rats, the 1.0 and 0.5 mg/kg dose supported reliable self-administration as indicated by discriminative responding. These rats reliably chose a lever that resulted in the delivery of these doses of cocaine over an inactive lever. Reinforced response rates were reduced when 0.25 mg/kg was the available dose and there was a loss of discriminative responding for some of the rats suggesting that it was close to threshold for self-administration. For rats that sustained a 70% depletion of dopamine in the medial prefrontal cortex, the dose-response curve was an inverse function across the entire dose range tested. In contrast to the data from the control rats, lesioned rats had a high rate of reinforced responses and demonstrated good discrimination for all doses including 0.25 mg/kg/infusion, suggesting a supersensitive response to the initial reward effect of cocaine. Another group of rats was first screened for reliable cocaine self-administration (0.5 mg/kg/infusion) and then subjected to either the prefrontal cortical 6-hydroxydopamine or sham lesion. Dose-response curves for cocaine self-administration were compared 14 days following the infusions. The lesioned rats responded reliably for low doses of cocaine that were unable to maintain responding in sham rats. These data support the hypothesis that the medial prefrontal cortex plays an important role in cocaine self-administration. PMID- 1905577 TI - Ischemic neuronal injury in the rat hippocampus following transient forebrain ischemia: evaluation using in vivo microdialysis. AB - Neuronal vulnerability to ischemia in the rat hippocampus was investigated by the measurement of high potassium evoked overflow of neurotransmitters using in vivo microdialysis. Changes in the extracellular level of amino acids caused by high potassium (100 mM) stimulation were measured on the 5th day after 20 min of forebrain ischemia, and the ratio of stimulated to basal levels or the peak concentration following the stimulation were correlated to neuronal activities. The responses to high potassium stimulation of glutamate and aspartate were reduced to 35-40% of the control values on the 5th day after 20 min ischemia, whereas the responses of gamma-aminobutyric acid (GABA) and taurine were not reduced on the 5th day after the ischemia. These results suggest that excitatory amino acid neurons (glutamatergic and aspartatergic) are more vulnerable than inhibitory amino acid neurons (GABAergic and taurinergic) in the hippocampus. Histologically, hippocampal CA1 pyramidal cells, which are believed to be glutamatergic or aspartatergic, demonstrated a marked neuronal necrosis on the 5th days after 20 min ischemia. Biochemical features revealed by high potassium stimulation may be an expression of 'delayed neuronal death' in the hippocampal CA1 area. PMID- 1905578 TI - 6-[18F]fluoro-L-dopa metabolism in MPTP-treated monkeys: assessment of tracer methodologies for positron emission tomography. AB - 6-[18F]Fluoro-L-DOPA (FDOPA) is an L-DOPA analog that is used to assess the functional integrity of central dopaminergic systems in vivo with positron emission tomography (PET). FDOPA metabolites from putamen of normal and MPTP treated monkeys were characterized to correlate FDOPA metabolism changes with those of the endogenous dopamine system. In MPTP-lesioned putamen, 6 [18F]fluorodopamine and dopamine levels were less than 2% those of controls. Increases in endogenous dopamine metabolism were reflected by similar increases in 6-[18F]fluorodopamine metabolites. These results suggest that changes in the central dopamine system biochemistry can be monitored in vivo with FDOPA and PET. PMID- 1905579 TI - Mother-to-child transmission of HTLV-1. AB - Transmission of HTLV-I via mother's milk has been confirmed by epidemiological studies and by animal experiments using carrier mother's milk and a marmoset. The prevalence rates of HTLV-I carriers in children born of carrier mothers in endemic areas and ATL families were higher than in three control groups of young people. Also, the prevalence rates of carrier mothers who were traced from previously identified carrier children in three groups (two endemic areas and ATL family members) were extremely high. When HTLV-I antigen-positive lymphocytes were detected in carrier mother's milk, the child infection rate was higher than in the cases where antigen-positive cells could not be detected in mother's milk. The number of infected cells present in carrier mother's milk was calculated and the volume of milk given to the baby from delivery to weaning was estimated. Then, an equivalent amount of carrier mother's milk was inoculated into a marmoset orally and this marmoset seroconverted 2.5 months after the inoculation. A campaign to stop carrier mothers from giving their breast milk to their babies has been started in Nagasaki. So far, this trial has been shown to be successful in the prevention of mother-to-child infection. PMID- 1905580 TI - The suppressive effect of a synthetic retroviral peptide on the human IFN gamma production is abrogated by the combined stimulation with IL-1 and IL-2. AB - Certain retroviral envelope proteins and peptides have been shown to be highly immunosuppressive. Recently, we have demonstrated that a synthetic 17 amino acid peptide (CKS-17*) homologous to a highly conserved region in the transmembrane portion of the envelope of several human or animal retroviruses suppresses the production of human interferon-gamma (IFN gamma) by human peripheral blood leukocytes (PBL). In the present investigation, we studied the role of exogenous IL-1 or IL-2, and IL-1 plus IL-2 on the suppressive action of CKS-17* in the production of IFN gamma. The results showed that preculture of PBL with CKS-17* reduced the production of IFN gamma in a dose-dependent manner. The addition of IL-1 or IL-2 reduced, in part, this suppression of IFN gamma production. Full abrogation of the inhibition attributable to CKS-17, however, occurred only when PBL precultured with CKS-17* were recultured with staphylococcus enterotoxin A (SEA) together with exogenous IL-1 plus IL-2. These results show that the inhibition of IFN-gamma production by CKS-17* is reversible. The findings indicate that cytokines can modulate certain of the immunosuppressive actions attributable to retroviruses or their components and suggest that some cytokines influence immunosuppressive consequences of retroviral infection. PMID- 1905581 TI - Inhibitory effect of monocytes on "lymphokine activated killer" (LAK) cell activity. AB - The effects of placing activated monocytes in the presence of LAK cells was investigated. It was shown that the addition of monocytes to a preparation of rIL2-stimulated lymphocytes decreased LAK cell activity. This inhibition is enhanced in the presence of rIFN gamma. To analyze the mechanisms of inhibition, monocytes and lymphocytes were cultured separately, on opposite sides of a porous membrane which allowed the passage of molecules. Under such conditions, monocytes inhibited the activity of LAK cells to the same degree that a mixed culture does, suggesting a possible role of diffusible factor(s). Neither indomethacin nor PGE2 fully inhibited LAK cell activity, indicating that PGE2 is not the major monocyte derived factor inhibiting LAK cell activity. It was also demonstrated that LAK cells can kill monocytes, but that IFN gamma can protect the monocyte from the toxic effect. This protective mechanism may be responsible for enhancing the inhibitory activity of monocytes. PMID- 1905582 TI - Regulation of the expression of major histocompatibility complex class I genes in human colorectal cancer. AB - Products encoded by the major histocompatibility complex class I genes are down regulated in many tumors. The under-representation of HLA antigens in human tumors is usually associated with a poor prognosis. In this report, the expression of HLA genes in human colorectal carcinomas was studied using HLA-A and HLA-B locus-specific probes. Over 50% of the colorectal carcinomas studied showed a reduction in the amount of steady-state HLA mRNA. For some carcinomas, non-coordinated regulation of the HLA-A and HLA-B genes was observed. The HLA expression in some, but not all cases, could be enhanced by gamma-interferon. Over 60% of the colorectal carcinomas also expressed high level of the c-myc oncogene mRNA. However, no correlation could be made between the increase of c myc expression and the down-regulation of the HLA genes. PMID- 1905584 TI - Inhibition of lactate dehydrogenase isoenzyme associated with anaerobic respiration in schistosomiasis intermediate host snails. AB - Lactate dehydrogenase isoenzyme (LD5) which is associated with anaerobic respiration was inhibited to a certain degree in Biomphalaria alexandrina snails, the intermediate host for Schistosoma mansoni. Urea and thiourea were used as inhibitors. The effect of LD5 inhibition on the mortality rate of infected Biomphalaria alexandrina snails and on the susceptibility of the snails to the trematode infection was also studied. PMID- 1905585 TI - Detection of antigenic cyst wall elements in Colpoda inflata: an immunoelectron microscopic study and immunoblotting identification of cyst wall polypeptides. AB - By using an antiserum against isolated cyst walls from resting cysts of the ciliate Colpoda inflata, cyst wall polypeptides have been identified by immunoblotting test. Likewise, an immunoelectron microscopical study on both complete resting cysts and isolated cyst walls to localize the cyst wall proteins recognized by the antiserum, has been carried out. The immunoblotting test showed that three main polypeptide bands were recognized by the antiserum, with tentative molecular weights of 61, 66 and 70 kDa respectively. This methodology provides a better identification of cyst wall proteins after electrophoretic separation of cyst wall samples from ciliate resting cysts. PMID- 1905583 TI - Immunogenicity of a non-class I MHC expressing murine tumor transfected with the influenza virus hemagglutinin or murine interleukin-2 genes. AB - The transfection of murine SP1 tumor cells with the hemagglutinin (HA) gene of influenza virus results, after fluorescent-activated cell sorting (FACS), in the selection of high-HA-expressing cell lines called H4A and H4B. Both lines fail to grow in syngeneic animals at doses that result in 100% tumor take of non transfected tumor cells. Both grow in immunosuppressed mice. SP1 and H4A or H4B cells express few class I major histocompatibility complex (MHC) antigens but do express class II IAk antigens. H4A or H4B cells engender a cytotoxic T lymphocyte (CTL) response but cannot protect against a challenge with SP1 cells. This CTL response is inhibited by anti-CD4 but not anti-CD8 antibodies. Using FACS, we were able to select a population (called H5AK5) with high class-I MHC antigen expression. Like H4A and H4B, H5AK5 cells fail to grow in syngeneic animals but do grow in immunosuppressed mice. However, unlike H4A or H4B, H5AK5 can induce protection against a challenge with 1 x 10(5) SP1 cells. These studies indicate that the immunogenicity of HA-transfected SP1 cells may correlate with the cell surface expression of class II MHC antigens. However, HA-expressing SP1 cells seem able to induce a protective response against a parent SP1 cell challenge only if they also express class I MHC antigens. This view is supported by the observations that SP1 cells expressing murine interleukin-2 do not express class I MHC antigens, fail to grow in syngeneic animals, do grow in immunosuppressed mice but do not protect against a challenge with parental SP1 cells. PMID- 1905587 TI - The effect of AZT on in vitro lymphokine-activated killer (LAK) activity in human immunodeficiency virus type-1 (HIV-1) infected individuals. AB - Human immunodeficiency virus type-1 (HIV-1)-infected individuals exhibit functional impairment in various forms of cell-mediated cytotoxicities (CMC) at all stages of disease. The purpose of this study was to determine (i) if peripheral blood mononuclear cells (PBMC) obtained from HIV-1-infected patients could be stimulated in vitro to yield lymphokine-activated killer (LAK) activity; (ii) if non-MHC-restricted gp120-specific CMC could be preserved; and (iii) what effect zidovudine (AZT) would have on LAK activity. Fourteen asymptomatic HIV-1 seropositive adults and five healthy seronegative adults (controls) were evaluated. PBMCs were isolated and incubated in media or supplemented with IL-2 for 4 or 72 hr. Lysis of the NK resistant target cell line, Daudi, was similar for the control and experimental group. The increase in activity after stimulation was elevated to a similar degree in both seronegative and seropositive groups (P less than 0.001). LAK activity was significantly decreased (P = 0.011) when AZT was added to LAK cultures. In addition, virus production may not have been completely inhibited by AZT in LAK cultures. Thus, PBMCs from asymptomatic HIV-1-infected patients could be stimulated to yield LAK activity. However, AZT can impair LAK generation. It is unclear if LAK activation results in virus production that cannot be inhibited by AZT in this system. Further definition in other patient populations is required prior to applying this information to clinical trials. PMID- 1905586 TI - Induction of thymocyte proliferation by supernatants from a mouse thymic epithelial cell line. AB - The thymic stroma plays a critical role in the generation of T lymphocytes by direct cell-to-cell contacts as well as by secreting growth factors or hormones. The thymic epithelial cells, responsible for thymic hormone secretion, include morphologically and antigenically distinct subpopulations that may exert different roles in thymocyte maturation. The recent development of thymic epithelial cell lines provided an interesting model for studying thymic epithelial influences on T cell differentiation. Treating mouse thymocytes by supernatants from one of TEC line (IT-76M1), we observed an induction of thymocyte proliferation and an increase in the percentages of CD4-/CD8- thymocytes. This proliferation was largely inhibited when thymocytes were incubated with IT-76M1 supernatants together with an anti-thymulin monoclonal antibody, but could be enhanced by pretreating growing epithelial cells by triiodothyronine. We suggest that among the target cells for thymulin within the thymus, some putative precursors of early phenotype might be included. PMID- 1905588 TI - H-2K molecules positively select V beta 17a+ CD4(-)8+ T cells in bone marrow and thymic chimeras. AB - Population size of V beta 17a brightly positive cells among CD4(-)8+ thymocytes was analyzed in thymic chimeras as well as bone marrow (BM) chimeras in which SWR/J mice were used as BM donors and various strains of mice including H-2Kb mutant (bm) mice as recipients. It was shown that the proportion of V beta 17a+ CD4(-)8+ thymocytes was determined by H-2K molecules expressed on thymic epithelial cells. The highest proportion was observed in Ks and Kb thymuses, the intermediate proportion in Ks/q and Kk, and the lowest in Kq thymuses. Fine analysis of the H-2Kbm molecules involved in the positive selection revealed that the region important to the selection was located on the beta-pleated floor of antigen recognition site. According to the three-dimensional class I structure, this site appears not to be directly accessible to the T cell antigen receptor. Thus, the present finding suggests that the substitutions of amino acids at this site alter the shape and charge of the peptide binding site and eventually influence the positive selection of the V beta 17a+ T cell repertoire during differentiation. PMID- 1905590 TI - High mitomycin C concentration in tumour tissue can be achieved by isolated liver perfusion in rats. AB - To enable the treatment of hepatic metastasis with higher, theoretically more effective, doses of systemically toxic anticancer drugs, an isolated liver perfusion (ILP) technique was developed in WAG/Ola rats. First, in a toxicity study the maximally tolerated dose (MTD) of mitomycin C (MMC) was determined for a 25-min ILP and for hepatic artery infusion (HAI) after the administration of a bolus dose. The MTD in the ILP setting (4.8 mg/kg) was 4 times that using HAI (1.2 mg/kg). Subsequently, in a rat colorectal hepatic-metastasis model, concentrations of MMC in tumour, liver, plasma and perfusate were measured during a 25-min ILP to investigate the expected pharmacokinetic advantage of ILP. The mean plasma level determined after ILP (1.2 as well as 4.8 mg/kg MMC) was significantly lower (P less than 0.001) than that obtained following HAI. This may explain both the absence of severe systemic toxicity and the higher MTD in ILP-treated groups. No significant difference in mean tumour and liver tissue concentrations of MMC were found when the groups treated with 1.2 mg/kg drug via HAI vs ILP were compared. The mean MMC concentration in tumour tissue was significantly higher (almost 5 times; P less than 0.05) in rats treated by ILP with the MTD (4.8 mg/kg) than in those treated via HAI with the MTD (1.2 mg/kg). ILP of MMC can be safely performed using a dose 4 times higher than the MTD in the HAI setting, leading to an almost 5-fold concentration of MMC in hepatic metastasis. ILP of MMC may therefore represent a promising therapy for metastasis confined to the liver. PMID- 1905591 TI - A prospective comparison of class IA, B, and C antiarrhythmic agents in combination with amiodarone in patients with inducible, sustained ventricular tachycardia. AB - BACKGROUND: Clinical experience suggests that combinations of antiarrhythmic agents provide more effective control of ventricular tachyarrhythmias than does therapy with single agents. METHODS AND RESULTS: Antiarrhythmic and electrophysiological effects of three class I antiarrhythmic agents, one from each subclass A, B, and C, were assessed in single use and in combination with amiodarone in patients with inducible, sustained ventricular tachycardia that was not suppressed by monotherapy with these agents. Thirty-one patients underwent an electrophysiology test on four occasions: at baseline; after 2-4 days of treatment with quinidine, mexiletine, or encainide; after 2 weeks of treatment with 1,200 mg/day amiodarone; and last, after 2-4 days of treatment with both amiodarone and the previously tested class I agent. The combination of a class I agent and amiodarone prevented the induction of sustained ventricular tachycardia in only one of 31 (3%) patients. Ventricular tachycardia became hemodynamically stable in 11 of 31 (34%) patients because of a marked prolongation in the tachycardia cycle length. It increased from 323 +/- 39 to 423 +/- 84 msec (n = 11, p less than 0.01) by adding encainide to amiodarone therapy, and it showed a tendency to lengthen when quinidine was added to amiodarone (from 373 +/- 77 to 425 +/- 58 msec; n = 10, NS). Each class I agent increased amiodarone-induced depression in myocardial conduction, but the extent of the additional depression seemed to differ among the three subclasses. Ventricular refractoriness was increased by all class I agents when used in combination with amiodarone, although not by mexiletine or encainide when used alone. CONCLUSIONS: Class I antiarrhythmic agents slow ventricular conduction and increase ventricular refractoriness when used in combination with amiodarone. When amiodarone and class I drugs by themselves do not suppress the induction of ventricular tachycardia, the combination of amiodarone and a class I agent seldom results in noninducibility; however, it often lengthens the ventricular tachycardia cycle length and may render the ventricular tachycardia hemodynamically stable. PMID- 1905589 TI - Phorbol ester plus calcium ionophore induces release of arachidonic acid from membrane phospholipids of a human B cell line. AB - Binding of LA350, a lymphoblastoid human B cell line, by phorbol myristate acetate (PMA) plus a calcium ionophore, either ionomycin or A23187, produced unique alterations in the release of arachidonic acid (AA) from cellular phospholipids. After equilibrium labeling of cells with radioactive fatty acids, [14C]AA demonstrated a selective enhanced release from the cells in response to the binding of PMA plus calcium ionophore as compared to the release of [14C]stearic acid (STE), [3H]oleic acid (OLE) and [3H]palmitic acid (PAL). The major phospholipid sources of the released [14C]AA were shown to be phosphatidylcholine, phosphatidylethanolamine, and phosphatidylinositol. The participation of protein kinase C (PKC) in the enhanced synergistic release of [14C]AA was demonstrated by the inhibition of the release by the PKC inhibitor, staurosporine. Approximately 2-6% of the labeled AA liberated was converted to 5 hydroxyeicosatetraenoic acid by an endogenous 5-lipoxygenase. Therefore during cell activation the B cell is capable of liberating AA via a PKC-dependent mechanism, implicating AA and/or its metabolites in signal transduction. PMID- 1905593 TI - Effective thrombolysis without marked plasminemia after bolus intravenous administration of vampire bat salivary plasminogen activator in rabbits. AB - BACKGROUND: The use of recombinant tissue-type plasminogen activator (t-PA) in thrombolytic therapy is frequently associated with significant fibrinogenolysis. In contrast, recombinant vampire bat salivary plasminogen activator (Bat-PA) displays strict fibrin specificity, an attribute that could be desirable in a fibrinolytic agent. METHODS AND RESULTS: The efficacy and fibrin selectivity of Bat-PA was evaluated and compared with that of t-PA using a rabbit model of femoral arterial thrombosis. Administration of 8.1, 14, and 42 nmol Bat-PA/kg by bolus intravenous injection restored flow in 50%, 75%, and 80% of the rabbits, respectively. The incidence of reperfusion after bolus intravenous injection of 14 and 42 nmol t-PA/kg was 15% and 78%, respectively. The maximal femoral artery reperfusion flows were equivalent after treatment with 42 nmol Bat-PA/kg or 42 nmol t-PA/kg, but the time to reach maximal flow for Bat-PA was approximately one half that of t-PA. Furthermore, the rapid restoration of flow by 42 nmol Bat PA/kg, in contrast to equimolar t-PA, was accomplished without fibrinogenolysis and with only small decreases in the plasminogen and alpha 2-antiplasmin levels. Equipotent doses of Bat-PA and t-PA both resulted in approximate 2.5-fold increases in the template bleeding times of aspirin-pretreated rabbits. The clearance of Bat-PA from rabbits exhibited biexponential elimination kinetics; approximately 80% was cleared by the relatively slow beta phase (half-life of 17.1 minutes). Overall, Bat-PA was cleared approximately fourfold slower than t PA. CONCLUSIONS: Bolus intravenous administration of Bat-PA would facilitate prompt initiation of thrombolytic therapy, and the avoidance of plasminemia could result in fewer and less severe bleeding complications. PMID- 1905594 TI - Plasminogen activator inhibitor-1 suppresses endogenous fibrinolysis in a canine model of pulmonary embolism. AB - BACKGROUND: Plasminogen activator inhibitor-1 (PAI-1), the specific, fast-acting inhibitor of tissue-type plasminogen activator (t-PA), binds to fibrin and has been found in high concentrations within arterial thrombi. These findings suggest that the localization of PAI-1 to a thrombus protects that same thrombus from fibrinolysis. In this study, clot-bound PAI-1 was assessed for its ability to suppress clot lysis in vivo. METHODS AND RESULTS: Autologous, canine whole blood clots were formed in the presence of increasing amounts of activated PAI-1 (0-30 micrograms/ml). Approximately 6-8% of the PAI-1 bound to the clots under the experimental conditions. Control and PAI-1-enriched clots containing iodine-125 labeled fibrin (ogen) were homogenized, washed to remove nonbound elements, and delivered to the lungs of anesthetized dogs where the homogenates subsequently underwent lysis by the endogeneous fibrinolytic system. 125I-labeled fibrin degradation products appeared in the blood of control animals within 10 minutes and were maximal by 90 minutes. PAI-1 reduced fibrin degradation product release in a dose-responsive manner at all times between 30 minutes and 5 hours (greater than or equal to 76% inhibition at 30 minutes, PAI-1 greater than or equal to 6 micrograms/ml). PAI-1 also suppressed D-dimer release from clots containing small amounts of human fibrin (ogen). t-PA administration attenuated the effects of PAI 1, whereas latent PAI-1 (20 micrograms/ml) had no effect on clot lysis. Blood levels of PA and PAI activity remained unaltered during these experiments. CONCLUSIONS: The results indicate that PAI-1 markedly inhibits endogenous fibrinolysis in vivo and, moreover, suggest that the localization of PAI-1 to a forming thrombus is an important physiological mechanism for subsequent thrombus stabilization. PMID- 1905592 TI - Effect of diltiazem on symptomatic and asymptomatic episodes of ST segment depression occurring during daily life and during exercise. AB - BACKGROUND: Silent myocardial ischemia is an adverse prognostic marker in patients with coronary disease; however, controlled data on the effect of treatment are sparse and contradictory, and the relations among the occurrence of ST segment depression, drug efficacy, and heart rate are unclear. METHODS AND RESULTS: Sixty patients with stable coronary artery disease, a positive treadmill exercise test and asymptomatic ST segment depression on ambulatory electrocardiographic recording were assessed in a multicenter, double-blind, placebo-controlled, cross-over trial. Treadmill exercise tests and 72-hour electrocardiographic recordings were obtained at the end of two 2-week treatment periods with sustained-release diltiazem 180 mg b.i.d. or equivalent placebo. Episodes of asymptomatic ST depression decreased by 50% or more in 70% of the patients from a median number of 4.5 (range, 0-19) to 1.5 (range, 0-13) (p = 0.0001); their cumulative duration also decreased from 78.5 (range, 0-60) to 24.5 (range, 0-411) minutes (p = 0.001). No circadian variation was found in the efficacy of diltiazem. The occurrence of ischemic type ST segment depression was modulated by changes in heart rate rather than by absolute heart rate. Diltiazem also improved exercise test end points but to a lesser extent. Time to ST segment depression increased to 341 +/- 148 from 296 +/- 154 seconds (p = 0.005). Although less frequent with diltiazem administration (45 versus 54 patients, p less than 0.03), exercise-induced ST depression was more often asymptomatic (98% versus 72% of patients, p less than 0.0001). CONCLUSIONS: Diltiazem reduces the frequency and severity of ischemic type ST depression in patients with stable coronary artery disease. PMID- 1905595 TI - Concurrent hydralazine administration prevents nitroglycerin-induced hemodynamic tolerance in experimental heart failure. AB - BACKGROUND: Organic nitrates such as nitroglycerin and isosorbide dinitrate are useful in the treatment of congestive heart failure (CHF), but tolerance develops rapidly during continuous administration. Because combination therapy of nitrate and hydralazine has been shown to provide both short- and long-term benefit but nitrate alone produces hemodynamic tolerance, we questioned whether hydralazine can preserve the favorable preload effects of nitroglycerin. METHODS AND RESULTS: Using an in vivo model of nitroglycerin tolerance in the CHF rat, we examined the effects of hydralazine bolus dosing during continuous nitroglycerin infusion. Continuous infusion of nitroglycerin alone (10 micrograms/min) produced initial reductions in left ventricular end-diastolic pressure of 40-50%, which returned to baseline by 8 hours (tolerance development). Coadministration of hydralazine (2 x 0.1 mg) maintained the effects of nitroglycerin infusion on left ventricular end-diastolic pressure (45% reduction at 10 hours). This hydralazine dose alone reduced left ventricular peak systolic pressure by approximately 12 +/- 3% but had no effect on left ventricular end-diastolic pressure. Hydralazine dosing did not affect steady-state plasma concentrations of nitroglycerin or metabolites, and hydralazine was unable to prevent nitroglycerin tolerance induced in vitro. CONCLUSIONS: The beneficial interaction of hydralazine on the preload effects of nitroglycerin may explain the long-term clinical efficacy of hydralazine/nitrate combination in CHF. Our results also suggest that the mechanism of in vivo nitrate tolerance in CHF may be systemic rather than vascular in origin. PMID- 1905598 TI - Large vessel occlusion, cerebral infarction and thrombocytopenia in the "primary" antiphospholipid syndrome. Response to anticoagulation. AB - A 65-year-old white female without lupus developed concurrent thrombocytopenia and disturbed arterial circulation to the brain and lower leg (a minor stroke and lower leg gangrene, necessitating amputation). Laboratory studies disclosed high levels of anticardiolipin antibodies. Anticoagulant treatment restored circulation in the remaining leg and also normalized platelet levels. This case emphasizes the importance of searching for anticardiolipin antibodies in unexplained thrombotic events. PMID- 1905596 TI - Induction of c-fos and c-myc mRNA expression by immunoglobulin G from patients with Graves' disease in thyrotrophin-dependent rat thyroid cell line (FRTL5). AB - The present study was conducted to evaluate effects of autoantibodies in patients with Graves' disease on induction of c-fos and c-myc mRNA expression in rat thyroid cell line (FRTL5). IgG fractions were isolated from 11 patients with Graves' disease, and six healthy subjects, with protein A-Sepharose. FRTL5 cells which had been grown to subconfluency and deprived of TSH for a week were exposed to the IgG for an hour. Expression of c-fos and c-myc mRNAs was examined by the Northern blot method using nick-translated v-fos and c-myc probes. C-fos and c myc transcripts were induced by IgGs from two patients with Graves' disease, which displayed much higher activities in assays for TSH binding inhibitor immunoglobulins, thyroid stimulating antibodies and thyroid growth-stimulating immunoglobulins, assessed by measuring inhibition of 125I-TSH binding to the TSH receptor, cAMP production and 3H-thymidine incorporation in FRTL5 cells, respectively, compared with those in the remaining patients. The induction of c fos and c-myc mRNAs by IgG from a patient with Graves' disease was suppressed by preincubation with IgGs from two patients with primary myxoedema who were known to have a blocking type TSH-receptor antibody. These data suggest that the binding of the antibodies to the TSH-receptor followed by cAMP production is related to the induction of c-fos and c-myc mRNAs and, thus, to the growth of FRTL5 cells. To our knowledge, this is the first report demonstrating that autoantibodies induce proto-oncogene mRNA expression. PMID- 1905597 TI - Physical and surgical principles governing carbon dioxide laser surgery on the skin. AB - Although the physical principles governing the safe delivery of coherent radiation are well established, these rules are broken as often as they are followed. Few surgeons take advantage of the increased precision afforded by the rapid superpulse mode. Through a misdirected sense of caution, many surgeons use dangerously low power outputs and choose power densities in the carbonization range. Surface ablation is often undertaken with a beam geometry suited only to thermal incision, thereby producing an array of ridges and gutters that must be flattened by a raster technique. Each sequential pass of the laser adds to the amount of unnecessary thermal injury. Finally, some surgeons still try to control the laser in delicate situations through turning down beam power rather than through the strategy of prolonging reaction time with gated pulses. Of course, simple observation of correct physical principles does not guarantee a successful outcome. Strategies are also required to ensure dextrous beam delivery and to minimize thermal injury within adjacent tissue. As in other forms of surgery, the dermatologic surgeon must learn how to control bleeding, gain exposure, delineate geographic margins, and control the depth of destruction. When these lessons are assimilated, wounds heal rapidly, and results are indistinguishable from normal tissue. PMID- 1905600 TI - Aminoaciduria as a marker of acute renal transplant rejection--a patient study. AB - Over 12 months, urine samples were systematically collected from 40 children who underwent renal transplantation for the treatment of end-stage renal disease. Sequential determinations of the excretion of individual amino acids relative to that of creatinine were carried out on 15 subjects. Nine of these (including three who sustained episodes of acute rejection) retained a native kidney in situ, while in six patients (including three who underwent an episode of acute rejection) both native kidneys had been removed. In both subgroups, the amino acid/creatinine ratios of early morning urine samples were higher shortly before clinical manifestations of acute rejection became evident than in patients who, following renal transplantation, had stable kidney function, chronic graft rejection, or acute tubular necrosis, with one exception: a patient with one native kidney in-situ in whom acute tubular necrosis developed immediately after transplantation. The amino acids showing the greatest increase included Thr, Ser, Gly, and Ala. These values fell dramatically immediately prior to the clinical episode of acute rejection, with Thr, Ala, and Phe showing the most consistent changes. These alterations in urinary amino acid excretion occurred several days before changes in urinary protein excretion or the serum concentrations of urea and creatinine, and may have a role to play in the monitoring of renal transplant recipients. PMID- 1905599 TI - Glycosaminoglycans in the synovial fluids of patients with juvenile rheumatoid arthritis. AB - A simple method was used to isolate hyaluronic acid (HA) and sulfated glycosaminoglycans from synovial fluids obtained from children with juvenile rheumatoid arthritis (JRA) and from normal age-matched controls. The bulk of the glycosaminoglycans present in both normal and pathologic synovial fluids consisted of hyaluronic acid and chondroitin 6-sulfate. The diseased synovial fluids showed a sharp decrease in the concentration of glycosaminoglycans when compared with normal controls. These findings are similar to those reported for the synovial fluid of adult patients with rheumatoid arthritis. PMID- 1905601 TI - Can oxygen consumption in blood in vitro be detected by a change in PCO2? AB - The PO2 measured in a sample of blood can be misleadingly low, owing to consumption of oxygen in vitro in patients with leukemia. The purpose of this study was to determine whether a rise in PCO2 in such blood could be a useful indication of consumption of oxygen in vitro. Because of the non-bocarbonate buffer capacity of blood and the carriage of CO2, mainly as bicarbonate, we reasoned that the rise in PCO2 would be too small to be helpful. Hence the quantitative relationship between the consumption of oxygen and the production of CO2 in blood was determined. Other reactions yielding CO2 (the titration of lactic acid) were monitored. Consumption of oxygen was stimulated in blood of normals in vitro by adding methylene blue (100 mumol/L); in addition, blood from four patients with leukemia was studied without additions. The rate of consumption of oxygen at 22 degrees C was linear over 60 min; the respiratory quotient was close to unity. The rise in PCO2 was small even when the fall in PO2 was 60 mmHg. We conclude that a rise in PCO2 is not a reliable way to diagnose consumption of oxygen in blood in vitro as patients may hyperventilate, making it very difficult to recognize a small rise in PCO2. PMID- 1905602 TI - A controlled trial of the cost benefit of computerized bayesian aminoglycoside administration. AB - We studied the effect of a bayesian pharmacokinetic dosing program on the outcome of aminoglycoside therapy in patients with clinical infections. Patients were randomized to a control (dosing based on physician choice; n = 75) or experimental group (dosing based on the bayesian program; n = 72). Both groups used serum aminoglycoside concentration data when making dosing decisions. Improved response rates were seen in the experimental (60%; 42/68) compared with the control group (48%; 36/68). A higher, but not statistically significant, incidence of toxicity was found in the control (7/75; 9.7%) versus the experimental group (4/72; 5.1%). Mean length of total hospital stay was significantly longer for patients in the control group (20.3 days) compared with the experimental group (16.0 days) (p = 0.028). The variables from multivariate analysis with a significant impact on length of stay were patient group and length of aminoglycoside therapy. On the basis of a reduced length of stay, a potential cost savings of $1311 per patient can be achieved. PMID- 1905603 TI - Detection of light chain restriction in chronic B-lymphoid leukaemia and B-non Hodgkin's lymphoma. AB - The determination of immunoglobulin light chain restriction using monoclonal and polyclonal antibodies is a rapid method for the detection of a neoplastic B-cell population. Cytocentrifuge preparates of mononuclear blood cells from 42 patients with chronic B-lymphoid leukaemia and of lymph node aspirates from 24 patients with B-non-Hodgkin's lymphoma were examined using the alkaline phosphatase antialkaline phosphatase (APAAP) method. Monoclonal antibodies from different commercial sources and rabbit polyclonal antibodies were used in this study. Staining with polyclonal antibodies demonstrated light chain restriction in 65 cases. The leukaemic cells of a patient with hairy cell leukaemia did not express light chain immunoglobulins. Monoclonal antibodies from two manufacturers demonstrated monotypic staining for light chains in all cases with light chain immunoglobulins. Monoclonal antibodies from four manufactures failed to show monotypic light chains in 5, 21, 25 and 28 of the 65 cases. All investigated antibodies detected a similar percentage of light chain-positive lymphocytes in 10 healthy persons. We conclude that not all investigated monoclonal antibodies are suitable for detection of light chain restriction in B-non-Hodgkin's lymphomas and chronic B-lymphoid leukaemias. However, using selected monoclonal antibodies or rabbit polyclonal antibodies the APAAP method is very sensitive for detection of light chain restriction in these disorders. PMID- 1905605 TI - The role of monkeys in the biology of dengue and yellow fever. PMID- 1905604 TI - The effect of anticoagulants on the size of platelets in blood smears in the course of time. AB - In this study we measured platelet size in blood smears using the Kontron Mop Videoplan (Kontron Electronic Group, Weesp, Holland). The blood smears were prepared at different times after phlebotomy; samples were collected in three different anticoagulants and 100 consecutive platelets were measured in each smear. A number of platelet parameters were determined, some of which were based on the log normal distribution of the platelet area. We found that the size of platelets in blood smears is also dependent on the time after phlebotomy and the anticoagulant used. This may be important for the comparison of platelet areas, a characteristic of various disorders. Our data indicate that the optimal interval after phlebotomy for preparation of blood smears is 2-5 min. PMID- 1905606 TI - Statistical models for prediction of arterial oxygen and carbon dioxide tensions during mechanical ventilation. AB - The possibility of constructing statistical models for prediction of alveolar oxygen and carbon dioxide tensions has been investigated in 20 mechanically ventilated patients in acute respiratory failure (ARF). Linear multiple regression analysis using PaCO2 and PaO2 as dependent variables was used to construct (a) models for individual patients, (b) models for specific diagnostic groups and (c) general models (all patients). The coefficient of determination (R2) was highest for the individual patient models (0.38-0.99) and lowest for the general models (0.28-0.49). In order to achieve a high predictive accuracy, models matching individual patients should be constructed on the basis of initial invasive blood gas measurement. Statistically derived models may bring better understanding of the behaviour of factors influencing arterial gas tensions in ARF and may be of value in the management of patients on mechanical ventilation. PMID- 1905607 TI - Comparison of the cartilage proteoglycan core protein synthesized by chondrocytes of different ages. AB - Chondrocytes of different ages synthesize proteoglycans which have structural differences in both the chondroitin sulfate and keratan sulfate glycosaminoglycans. In order to ascertain whether age-dependent differences also occur in the core protein, the chick limb bud mesenchymal cell culture system was utilized to analyze newly synthesized proteoglycan core protein from undifferentiated mesenchymal cells (day 1 and 2), newly differentiated cartilage (day 4), mature cartilage (day 8), and senescent cartilage (day 16). The core protein synthesized at various times was identified by radiolabeling with [3H]leucine and [35S]sulfate immediately prior to extraction and purification. The sizes of the various core protein preparations were compared by electrophoresis on a 3% polyacrylamide gel after partial deglycosylation with chondroitinase AC and keratanase. The proteoglycans from day 4, 8, and 16 cultures each give rise to a single band of approximately 475,000 daltons. The proteoglycans from day 1 and 2 cultures also give rise to the 475,000 dalton band, but each contains several other components which produce a smear of high molecular weight material on the gel. The monomer proteoglycans were incubated with cyanogen bromide and the resultant peptides separated by electrophoresis on a 5-17.5% polyacrylamide gel. The peptide displays of core proteins synthesized on days 4, 8 and 16 are virtually identical in terms of the number and electrophoretic distribution of the core protein peptides. In contrast, proteoglycan core proteins from day 1 and day 2 cultures give rise to peptide displays which resemble those from older cultures in some respects but have distinct features as well. The absence of structural variation in the newly synthesized proteoglycan core proteins from cartilage of different ages suggests that the age-related changes in the structure of the intact proteoglycans result from differences in the glycosaminoglycan biosynthetic machinery rather than alterations in the acceptor molecule (i.e., the core protein). PMID- 1905608 TI - Age-related differences in the metabolism of proteoglycans in bovine articular cartilage explants maintained in the presence of insulin-like growth factor I. AB - Articular cartilage explants from bovine calf and steer were cultured for up to 19 days in medium with or without 20% fetal bovine serum (FBS) or insulin-like growth factor I (IGF-I). Lower concentrations of IGF-I were required for maximal stimulation of PG synthesis in calf than in steer. In calf, but not in steer, IGF I was as effective as 20% FBS in stimulating PG synthesis. The stimulation by IGF I or FBS was not accompanied at either age by alterations in the composition of the aggregating PGs nor by changes in the proportions of CS-rich and CS-poor PG subpopulations. In calf, IGF-I and FBS did not markedly alter the rate of turnover of either the 35S-PGs synthesized in vitro or the unlabeled PGs. In steer, explants cultured in the absence of IGF-I or FBS exhibited very fast rates of turnover and depletion of matrix PG with time; IGF-I and FBS were both effective in reducing the turnover rate of 35S-PGs and unlabeled PGs and in preventing PG depletion. PMID- 1905611 TI - Peripheral chemosensitivity assessed by the modified transient O2 test in female twins. AB - To evaluate genetic influence on the control of breathing in adult women, we measured, in healthy female twins, ventilatory responses to isocapnic progressive hypoxia and hyperoxic progressive hypercapnia, and the withdrawal response (the modified transient O2 test) which is considered to selectively reflect peripheral chemoreceptor activity. The withdrawal response was obtained as the magnitude of initial depression in ventilation induced by two breaths of O2 from steady-state hypercapnic hypoxia. Nine monozygotic twin pairs, aged 44 +/- SD17 years, and 7 dizygotic twin pairs, aged 39 +/- 8 years, were studied. Mean values for ventilatory responses to hypoxia and hypercapnia, and the withdrawal response were not different between MZ and DZ. The within-pair variance ratio (VDZ/VMZ) for the withdrawal response was significantly greater than one (p less than 0.05), although neither VDZ/VMZ for the hypoxic response nor that for the hypercapnic response was greater than one. These observations suggest that the peripheral chemosensitivity is influenced by genetic factors even in adult women, including aged subjects, when genetic influence is not apparent in the ventilatory responses to progressive hypoxia and hypercapnia. PMID- 1905609 TI - Implants of keloid and hypertrophic scars into the athymic nude mouse: changes in the glycosaminoglycans of the implants. AB - Studies have been made of the glycosaminoglycan (GAG) composition of implants of keloid and hypertrophic scars in athymic nude mice in order to evaluate these implants as a model for studies of causation and therapy of these abnormal human scars. Changes in weight of implanted tissue were also recorded. Pieces of keloid, hypertrophic scar or normal human skin were placed in subcutaneous pockets of athymic nude mice and left for various times up to 246 days. The uronic acid content of the scar implants did not change significantly until after 80 days when the level decreased; the uronic acid level of normal skin increased slightly during the 110 days studied. The initially high percentage of chondroitin-4-sulfate of keloid and hypertrophic scar tissue decreased in the implants (averaging a 50% decrease at 164 days for keloids and at 176 days for hypertrophic scars). The average weight of the scar implants increased slightly after implantation and then decreased when expressed either as wet or dry weight. The regression lines of weight on time indicated an average loss of 50% dry weight at 66 days for keloid implants and 68 days for hypertrophic scars. Normal human skin increased in net weight until 20 days and dry weight until 40 days and then decreased, losing about 20% of weight (either wet or dry) at 110 days. On the basis of the glycosaminoglycan changes, the model should be useful for short term studies of therapy and causation. PMID- 1905612 TI - Determination of the optimal pressure support level evaluated by measuring transdiaphragmatic pressure. AB - The purpose of this study was to determine the optimum pressure support (PS) in six patients with respiratory failure. Esophageal pressure (Pe), gastric pressure (Pg), airway pressure, and transdiaphragmatic pressure (Pdi), obtained by subtracting Pe from Pg, were measured using a newly developed multiluminal nasogastric catheter. For each patient, different PS levels were selected every 20 minutes, and measurements were made at each PS level. We defined the optimum PS level as the level that showed the minimum Pe value. Respiratory rate (RR) decreased and tidal volume (VT) increased with an increase in PS level. RR and VT at the optimum PS were 19.7 +/- 5.5 breaths per minute and 11.7 +/- 4.5 ml/kg, respectively. Pdi decreased linearly with increasing PS level in all patients. Mean Pdi at the optimum Ps was 4.2 +/- 1.2 cm H2O. Based on the relationship between Pdi and PS level, we constructed an equation to estimate the optimum PS level as follows: Optimum PS level = [( Pdi during T-piece mode] - 4)/0.8. We conclude that Pdi measurement is helpful for titrating the required PS level. PMID- 1905610 TI - Collagens of the chicken eggshell membranes. AB - An immunohistochemical analysis of the eggshell membranes shows the occurrence of type X collagen while type I collagen was not detected by using an appropriate monoclonal antibody with untreated shell membranes. A positive immuno-reaction for type I collagen was obtained after digestion of the shell membranes with pepsin. These observations indicate the possibility that type I collagen epitope was masked by type X collagen and that type X collagen may serve as an inhibitory boundary for biomineralization. PMID- 1905613 TI - Normal values and ranges for ventilation and breathing pattern at maximal exercise. AB - Assessment of the breathing pattern at maximal exercise in patients is limited because the range of ventilatory responses (minute ventilation; tidal volume; respiratory rate) at maximal exercise in normal humans is unknown. We studied 231 normal subjects (120 women; 111 men) equally distributed according to age from 20 to 80 years. Each subject performed a progressive incremental cycle ergometer exercise test to their symptom-limited maximum. Mean ventilation at the end of exercise (Vemax) was significantly higher in men (mean +/- SD, 97 +/- 25 L/min) than in women (69 +/- 22 L/min) (p less than 0.001). Minute ventilation at the end of exercise as a fraction of predicted maximal voluntary ventilation (Vemax/MVV) for all subjects was 0.61 +/- 0.14 (range, 0.28 to 1.02). There was no difference in Vemax/MVV between men (0.62 +/- 0.14) and women (0.59 +/- 0.14). Tidal volume at the end of exercise (Vtmax) was higher in men (2.70 +/- 0.48 L) than in women (1.92 +/- 0.41 L) (p less than 0.001). Any differences in Vtmax between men and women disappeared when Vtmax was corrected for baseline FVC. Respiratory rate at the end of exercise (RRmax) was 36.1 +/- 9.2 breaths per minute for all subjects. There was no difference in RRmax between men and women. The Vemax correlated best with carbon dioxide output at the end of exercise (r = 0.91; p less than 0.001) and with maximal oxygen uptake (r = 0.90; p less than 0.001) for all subjects. This study of a large group of subjects has demonstrated the wide range of possible breathing patterns which are adopted during exercise and has provided a wide range of "normal" responses which must be taken into consideration when maximal ventilatory data from exercise tests are analyzed. PMID- 1905614 TI - Pharmacologic elevation of blood inorganic phosphate in hypoxemic patients with COPD. AB - We have shown that in patients with COPD, myocardial efficiency during exercise is enhanced following acute elevations of plasma phosphate (Pi). A decrease in Hb O2 affinity (increase in P50) was not responsible for the improvement. We postulated that the physiologic benefit was due to the acute reversal of a subclinical myocardial Pi depletion. To further test this hypothesis in a chronic state, we studied nine stable hypoxemic (PaO2 = 64 +/- 2 mm Hg [+/- SEM]) patients with COPD over five weeks: two weeks at normal plasma Pi; and three weeks at elevated plasma Pi, induced by etidronate disodium (Didronel; 750 mg orally daily). Administration of etidronate disodium increased (p less than 0.05) plasma level of Pi (4.4 +/- 0.2 to 5.8 +/- 0.1 mg/dl), RBC level of Pi (3.1 +/- 0.2 to 4.1 +/- 0.2 mg/dl), RBC level of 2,3-DPG (16.2 +/- 1.1 to 21.3 g+/- 1.3 mumol/g of Hb) and P50 (23.7 +/- 0.5 to 26.0 +/- 0.8 mm Hg). At the end of the treatment, the widening of the C(a-v)O2 with exercise (7.1 +/- 0.8 to 8.9 +/- 0.6 ml/dl) was less pronounced than under control conditions (6.9 +/- 0.4 to 10.1 +/- 0.6 ml/dl; p less than 0.02); concomitantly, the crossover point (COP; the PaO2 below which a rightward-shifted Hb-O2 curve causes the C(a-v)O2 to become narrower rather than wider) increased (37 +/- 2 to 49 +/- 1 mm Hg). Indicators of myocardial work efficiency were not affected by etidronate disodium at rest or during exercise. We postulate that during exercise the potential beneficial effect of the rightward shift of the Hb-O2 curve upon cardiac function was negated by the fall of PaO2 to or below the COP level, a situation which would limit increases in tissue O2 extraction. PMID- 1905615 TI - Coronary thrombolysis with recombinant tissue plasminogen activator. Intracoronary vs intravenous administration. AB - We employed a canine model of coronary thrombosis, induced by injection of radioactive blood clot, via a catheter placed in the left anterior descending coronary artery, to compare effects of recombinant tissue plasminogen activator (rtPA) administered intravenously and administered directly into the coronary circulation. A control group did not receive rtPA. Compared with controls, both rtPA regimens induced coronary thrombolysis. However, compared with intravenous administration, rate and extent of coronary thrombolysis were increased with intracoronary administration. Most likely, the enhanced thrombolysis with intracoronary administration is explained by an increase in delivery of the drug to the thrombus. PMID- 1905616 TI - Respiratory patterns after cholecystectomy. Effects of posture and CO2 stimulation. AB - A marked reduction in the ratio of abdominal to rib cage motion has been observed after upper abdominal surgery. This study seeks to determine the effects on respiratory pattern of stimulation with CO2 and a change in posture from supine to semirecumbent posture (hips flexed, head of bed elevated at 30 degrees to the horizontal) in patients having undergone cholecystectomy. Canopy spirometry and respiratory inductive plethysmography were used to measure minute ventilation, tidal volume, and rib cage and abdominal motion in 14 otherwise healthy women, prior to elective cholecystectomy and on the first and third postoperative days. Preoperatively, the relative contribution of the chest wall compartment to tidal volume (Vc/VT) was increased both by moving from the supine to the semirecumbent posture and by stimulation with 4 percent inhaled CO2. On the first postoperative day, there was a reduction in abdominal motion. In contrast to what happened in the preoperative period, there was no change in the relative contribution of the rib cage and abdomen when the patients moved from the supine to semirecumbent position. With CO2 stimulation, there was a further increase in the already increased absolute tidal volume of the chest. On the third postoperative day, there was an increase in abdominal motion in the supine and sitting position and during 4 percent CO2 stimulation. These results demonstrate that the response to a change in posture and to 4 percent CO2 stimulation are markedly altered in the postoperative period by the reduction in abdominal motion. PMID- 1905617 TI - Ventricular tachycardia with congenital ventricular diverticulum. AB - A 24-year-old man presented with symptomatic, recurrent, sustained ventricular tachycardia (VT). He was found to have a basal inferior left ventricular diverticulum. His sustained VT was reproduced by programmed electrical stimulation and was unresponsive to procainamide, tocainide, propafenone, and flecainide. Endocardial mapping followed by resection and cryoablative surgery was performed. The patient had only one recurrence after 18 months, with subsequent control with procainamide for over 14 months. PMID- 1905618 TI - Defining the proper role for self-administered sublingual nitroglycerin. A survey of physicians and patients. AB - Within a half-year period, we encountered six cases of patients harmed by the adverse effects of self-administered nitroglycerin--syncope, delayed definitive medical care, and the worsening of nonischemic symptoms. We therefore surveyed 112 patients after a remote myocardial infarction, and 121 cardiologists and internists, regarding the use of sublingual nitroglycerin. Of the physicians, 84 percent routinely prescribed nitroglycerin to patients after a myocardial infarction, and 79 percent of the patients had the tablets available (83 percent of these, at all times). Most patients used the tablets less than once per month, and 37 percent of the patients who always carried nitroglycerin had not used it at all during the preceding year. Although 89 percent of the patients claimed to know when to use the drug, 57 percent had used it or would use it for symptoms such as dizziness, rapid heartbeat, or presyncope. All patients having nitroglycerin claimed it relieved their symptoms, even if the relief was only partial, the time elapsed until relief could not be specified, and the symptoms were of a type unlikely to be relieved by the drug. We suggest that the practice of routinely prescribing nitroglycerin to patients after a myocardial infarction should be reassessed. PMID- 1905619 TI - An analysis of sequential physiologic changes in hypoxic cor pulmonale during long-term oxygen therapy. AB - Physiologic changes were studied retrospectively in 37 patients with hypoxic cor pulmonale who died during long-term oxygen therapy (LTOT). The subjects were assessed during periods of clinical stability for each year on LTOT. At the onset of treatment, their mean age (+/- SEM) was 60.0 +/- 1.3 years, and at the time of death, they were aged 65.0 +/- 1.3 years. The median duration of LTOT was five years. For each year leading up to death, mean values of FEV1, PaO2, and PaCO2 were obtained. A rate of decline of FEV1 of 73 +/- 10 ml/yr was observed, and this was accompanied by a decline in PaO2 of 0.47 +/- 0.01 kPa/yr. Patients died with a mean FEV1 of 0.55 +/- 0.04 L and a PaO2 of 5.1 +/- 0.2 kPa. A small rise in PaCO2 occurred, on average 0.25 +/- 0.09 kPa/yr, throughout the study, but accelerating in many cases during the three years before death. Hypoxic cor pulmonale appears to be associated with a rapid deterioration in airway function, a steady decline in PaO2, and a slow rise in PaCO2 during the years leading up to death. These physiologic changes measured in a stable clinical state while breathing air appear to occur in spite of LTOT. The LTOT may merely prevent death from episodes of severe hypoxemia while the pathophysiologic changes in the lung progress. Hence the benefit to be expected from LTOT is only temporary. Generally, those patients with lower levels of FEV1 will obtain diminishing clinical benefit, inversely related to the severity of airflow obstruction at the time of commencement of LTOT. PMID- 1905620 TI - Direct mechanical ventricular actuation for cardiac arrest in humans. A clinical feasibility trial. AB - Direct mechanical ventricular actuation (DMVA) is a non-blood-contacting method of biventricular cardiac massage which may be applied expediently for total circulatory support. The purpose of this study was to assess the feasibility of DMVA application for patients suffering refractory cardiac arrest. Following informed consent, DMVA was applied in 22 patients. Vascular access for hemodynamic monitoring was possible in only 12 patients, whose outcomes serve as the basis for this report. The mean age of the patients was 48.2 +/- 4.2 years (seven men; five women). The average time from witnessed cardiac arrest to DMVA application was 81 +/- 9 minutes. Application took less than two minutes from the time of skin incision and resulted in immediate hemodynamic improvement. Systolic and diastolic blood pressures averaged 78 +/- 4 and 41 +/- 4 mm Hg, respectively, with a mean cardiac output of 3.14 +/- 0.18 L/min during a mean of 228 +/- 84 minutes of circulatory support (range, 25 minutes to 18 hours). In selected cases the device was temporarily removed for 2 to 3 minutes and open-chest cardiac massage (OCCM) performed at similar compression rates. DMVA increased arterial pressures 65 percent and cardiac output 190 percent compared to OCCM. Initial arterial pH (7.12 +/- 0.04) improved by the time the device was removed (7.24 +/- 0.05). Serum lactate levels decreased from 18.0 +/- 2.3 mumol/L to 14.9 +/- 2.9 mumol/L. Four patients were successfully defibrillated: two had inadequate cardiac function and died within 1 h, and two were successfully resuscitated, but later died from cardiac failure and respiratory insufficiency. Another patient regained normal neurologic function during DMVA and was successfully bridged to cardiopulmonary bypass for emergent coronary artery bypass grafting, but died later from myocardial infarction. There were only two complications: (1) a cardiac laceration during pericardiotomy (1/22 patients); and (2) a ventricular rupture during OCCM (1/22). No complication resulted from the device. We found DMVA to be a feasible method for acute cardiovascular stabilization in victims suffering refractory cardiac arrest. Human clinical trials employing earlier DMVA application are required to determine its resuscitative potential. PMID- 1905621 TI - Effect of aldose reductase inhibition on resistance to ischemic conduction block in diabetic subjects. AB - OBJECTIVE: To study the effect of aldose reductase inhibition with ponalrestat on resistance to ischemic conduction block (RICB) in diabetic subjects. RESEARCH DESIGN AND METHODS: Twenty-one healthy diabetic subjects without neuropathy were studied. Subjects were randomized to take either a double-blind trial of 600 mg ponalrestat or placebo once daily for 6 wk. The median nerve action potential (MNAP) and conduction velocity (NCV), before and after 20 min of forearm ischemia, were measured at the start and finish of the study. RESULTS: RICB (MNAP remaining after ischemia) decreased from 39.5 to 29.4% in the ponalrestat-treated group (P less than 0.05) and increased from 48.1 +/- 10.2 to 49.5 +/- 6.5% in the placebo-treated group. MNAP and NCV were unchanged in both groups. CONCLUSIONS: Aldose reductase inhibition with ponalrestat partly reverses RICB in diabetes, perhaps by improving nerve hypoxia or reducing nerve energy substrates. PMID- 1905623 TI - Soil sorption of 20 PCB congeners and six chlorobenzenes. AB - The soil sorption of six chlorobenzenes and 20 PCB congeners was studied by allowing aqueous trace solutions (ppb) of transformer fluids to equilibrate with 3-6 different soils. Linear relations were found between distribution constants and soil organic carbon content. Sorption was favored by a high degree of chlorination and the absence of ortho-substitution in the biphenyl. Sorption kinetics seemed to be first-order controlled (two steps) with rate constants in the order of many hours. We present correlations between sorption data and published physical data, which will be useful for modeling the transport and the fate of PCBs and chlorobenzenes in the environment. PMID- 1905622 TI - [Interactions between digitoxin, flecainide and prajmalium bitartrate?]. PMID- 1905624 TI - Cerebral hemisphere memory for manual object handling: an intracarotid Amytal study. AB - The memory capacity of the cerebral hemisphere for manual object handling was studied during preoperative, intracarotid Amytal testing for hemisphere speech and memory in 32 patients with intractable partial epilepsy. The tactile stereognostic memory was tested non-visually before and after amobarbital injection. Two common objects, one in each hand, were given to the patient with the request to identify each by manipulation, but not to name it. Before injection, object handling was carried out correctly by both hands. After injection, while the patient was hemiplegic, the dominant hemisphere executed the object handling correctly; the non-dominant hemisphere, however, did it less properly. Free verbal recall of the object presented before the injection was correct in 85%. The free verbal recall of the postinjection objects was much lower; 22% for the speech-dominant, and only 3% for the non-dominant hemisphere. Tactile, non-visual recognition gave a memory score of 41% for the speech dominant, and 13% for the opposite hemisphere. An epileptic lesion in the dominant hemisphere impaired the memory performance of that hemisphere compared to the non-lesioned group. PMID- 1905625 TI - AHR-12245: a potential anti-absence drug. AB - AHR-12245, 2-(4-chlorophenyl)-3H-imadazo[4,5-b]pyridine-3-acetamid, ethosuximide, Na valproate, phenytoin, and clonazepam were evaluated in mice and rats with a battery of well-standardized anticonvulsant test procedures. The results obtained indicate that the anticonvulsant profile of AHR-12245 is similar to that for ethosuximide and clonazepam. AHR-12245 is effective in nontoxic intraperitoneal doses in mice by the maximal electroshock seizure (MES), pentylenetatrazol (s.c. PTZ), bicuculline, and picrotoxin tests but ineffective against strychnine induced seizures; it is effective after nontoxic oral doses in both mice and rats by the s.c. PTZ test and ineffective by the MES test. The candidate antiepileptic substance was also ineffective against seizures induced in amygdala and corneally kindled rats. The PIs for AHR-12245 by the s.c. PTZ test were 4.5 to 12 times higher than those for the prototype agents, except that for clonazepam when administered orally in mice. The in vitro studies indicate that AHR-12245 is a weak inhibitor of benzodiazepine (BDZ) receptor binding but does inhibit adenosine uptake. These results indicate that AHR-12245 is a relatively nontoxic agent with a profile of anticonvulsant action which suggests it should be useful in generalized absence seizures. PMID- 1905627 TI - Production of neuropeptides by inflammatory cells within the granulomas of murine schistosomiasis mansoni. PMID- 1905628 TI - Accelerated cholesteryl ester transfer in patients with insulin-dependent diabetes mellitus. AB - Abnormalities in cholesteryl ester transfer (CET) may play a role in the development of diabetic arterial vascular complications. To assess this important step systematically in reverse cholesterol transport, we have studied 20 treated, clinically stable, normolipidaemic patients. Contrary to the impairment in CET described previously in NIDDM, the mass of CE transferred from HDL to VLDL + LDL was significantly greater in IDDM patients than in controls at 1,2, and 4 h (P less than 0.001). When the d less than 1.063 plasma fractions from IDDM subjects were combined with controls d less than 1.063 fractions, an accelerated CET response was observed which was identical to that found in intact IDDM plasma. This finding, which indicates that this disturbance in CET was associated with the acceptor lipoproteins, was confirmed when we found that it was reproduced by the addition of IDDM VLDL and not LDL to control d greater than 1.063 fractions. Changes observed in lipoprotein core lipid composition were consistent with accelerated CET occurring in IDDM in vivo: the TG/CE core lipid ratio was decreased in VLDL from six subjects (diabetic 9.5 +/- 0.8 vs control 12.9 +/- 3.4; P less than 0.1) and increased in their HDL (diabetic 0.55 +/- 0.11 vs control 0.42 +/- 0.04; P less than 0.025). No correlation was demonstrable between estimates of diabetic control (glycoalbumin, fasting glucose) and CET. These data indicate that CET may be abnormally increased in normolipidaemic IDDM patients. A defect of this type may be atherogenic because it increases the number of lipoprotein particles in plasma which resemble cholesteryl ester enriched chylomicron and VLDL remnants but whose normal receptor-mediated catabolism may be altered. PMID- 1905626 TI - Activity of antiseptics against biofilms of mixed bacterial species growing on silicone surfaces. AB - As part of a programme to establish the relative merits of antiseptics that are used as bladder instillations to control urinary tract infections in patients with indwelling catheters, the activity of five such formulations were tested against dense (10(9) cfu/cm2) mixed biofilms composed of Citrobacter diversus, Pseudomonas aeruginosa and Enterococcus faecalis growing on silicone discs. All three species were resistant to chlorhexidine (200 mg/l) and povidone-iodine (1% v/v) in the biofilm mode of growth, whereas these agents rapidly eliminated viable cells from urine suspensions of the mixed community. Lactic acid (1% v/v) produced a 1 log reduction of the biofilm population within 30 min of exposure. The mandelic acid (1% w/v) and mandelic acid (0.5% w/v)/lactic acid (0.5% v/v) mixture proved to be the most effective in eliminating the biofilm organisms. It is suggested that these latter solutions should now be tested for efficacy in bladder washouts against urinary tract infections in catheterized patients. PMID- 1905630 TI - Effect of low protein diet on the renal response to meat ingestion in diabetic nephropathy. AB - We measured the renal haemodynamic and proteinuric response to a meat meal (MM) in ten persistently proteinuric insulin-dependent diabetic patients in a randomized cross-over study of 3 weeks on low protein diet (LPD) or normal protein intake (NPD). On LPD, protein intake (0.64 +/- 0.05 vs 1.15 +/- 0.09 g kg 1 body weight (BW) per day, P less than 0.001), plasma urea (6.6 +/- 1.3 vs 11.0 +/- 2.0 mmol l-1, P less than 0.01) and urea appearance (0.06 +/- 0.01 vs 0.16 +/ 0.03 gN kg-1 body weight per day, P less than 0.001) were lower. Baseline glomerular filtration rate (GFR), renal plasma flow (RPF) and renal vascular resistance (RVR) were similar on the two diets and there were no significant average changes in these variables after the meat meal on either diet (NPD, before vs after MM: GFR: 67 +/- 11 vs 71 +/- 13 ml min-1 1.73 m-2; RPF: 479 +/- 70 vs 512 +/- 81 ml min-1 1.73 m-2; RVR: 181 +/- 45 vs 179 +/- 52 mmHg min-1 l 1); (LPD, before vs after MM: GFR: 64 +/- 10 vs 67 +/- 11 ml min-1 1.73 m-2; RPF: 506 +/- 60 vs 533 + 52 ml min-1 1.73 m-2; RVR: 151 +/- 28 vs 146 +/- 32 mmHg min 1 l-1). However, all patients with baseline GFR above 60 ml min-1 1.73 m-2 showed a GFR rise in response to the meat meal on both diets, while patients with lower baseline values tended to reduce their GRF.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1905629 TI - Decreased insulin secretory capacity and normal pancreatic B-cell glucose sensitivity in non-obese patients with NIDDM. AB - We investigated the dose-response characteristics of glucose-induced insulin release and the influence of hyperglycaemia on arginine-induced insulin secretion in eight non-obese subjects with NIDDM and in eight non-diabetic volunteers. Plasma C-peptide levels, achieved during 60 min hyperglycaemic clamps with and without the infusion of a primed continuous infusion of arginine (infusion rate 15 mg kg-1 min-1) during the last 30 min, were analysed with a modified Michaelis Menten equation. The insulin secretory capacity (Vmax) for glucose-stimulated insulin release showed a trend towards a negative correlation with the fasting blood glucose in the NIDDM subjects (r = 0.68, P = 0.6); it was lower than the Vmax of non-diabetic controls (2.2 +/- 0.2 vs 4.2 +/- 0.4 nmol l-1 respectively; P less than 0.001). The ED50 (half maximal stimulating blood glucose concentration) of the second-phase glucose-stimulated insulin release (determined from the plasma C-peptide levels at 60 min) was not significantly different from the ED50 of the controls (11.9 +/- 0.8 vs 13.3 +/- 1.9 mmol l-1 respectively; P greater than 0.2). Combined glucose-arginine stimulation significantly increased insulin release. The Vmax for both phases were significantly lower in NIDDM patients than in controls (2.3 +/- 0.2 vs 5.0 +/- 0.9 and 3.8 +/- 0.5 vs 8.5 +/- 0.9 nmol l-1 respectively; P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1905631 TI - Increased removal of remnants of triglyceride-rich lipoproteins on a diet rich in polyunsaturated fatty acids. AB - We studied the effect of two diets, one rich in polyunsaturated and the other in saturated fatty acids, on the postprandial processing of exogenous and endogenous triglyceride-rich lipoproteins (chylomicrons, very-low-density lipoproteins, and their remnants). For this purpose, 12 normolipidaemic young volunteers were fed, in a cross-over design of 9 days on each diet, either a diet rich in saturated fat (21% of their daily energy intake from saturated fat, 12% from monounsaturated fat, and 3% from polyunsaturated fat) or a diet rich in polyunsaturated fat (10% saturated fat, 9% monounsaturated fat, and 18% polyunsaturated fat) (P/S ratios 0.14 and 1.8, respectively). On the last day of each dietary period blood samples were drawn six times over a 24-h period for determination, by densitometric scanning of SDS gels, of the diurnal pattern of apoprotein B-48 and B-100 in the d less than 1.019 g ml-1 fractions, as estimates for the processing of chylomicrons and very-low-density lipoproteins. In addition to the usual decrease in the fasting and diurnal concentrations of total serum cholesterol and of cholesterol in the low-density lipoprotein fractions (between 15 and 21%), the diet rich in polyunsaturated fat resulted in 43% lower daily concentrations of chylomicrons and their remnants. This was due to differences in the clearance rate of chylomicrons and their remnants, rather than to differences in the absorption rate of exogenous fat. In addition, the concentrations of very low density lipoproteins and their remnants during the day were 20% lower on the diet rich in polyunsaturated fat.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1905632 TI - Acute effects of HMG-CoA reductase inhibitors on biliary lipids in patients with interrupted enterohepatic circulation. AB - HMG-CoA reductase inhibitors decrease serum cholesterol by inhibiting hepatic cholesterol synthesis, but their influence on biliary lipids is not well characterized. In the present study Pravastatin (80 mg) was administered as a single oral dose to 10 patients with external bile fistula, after 1 week of interruption of the enterohepatic circulation, in order to assess the effect of inhibition of hepatic cholesterol synthesis on biliary lipids in conditions of stimulated bile acid synthesis. Bile was collected every hour for 12 h. On the day before, the same procedure was applied with a placebo, and collected bile used as control. Pravastatin decreased both bile acid and phospholipid concentration to about 60% of basal values; this change was still significant after 10 h. Cholesterol concentration was also decreased to about 70% of basal values, but this change was significant only from the 5th to the 7th h. The per cent of cholic and chenodeoxycholic acid was not affected by the drug, but the ratio of glyco- to tauroconjugated bile acids was decreased to about half the initial values. Bilirubin concentration exhibited a late increase, suggesting a reduction in the bile flow. These results suggest that, in patients with interrupted enterohepatic circulation, biliary excretion of bile acids can be largely dependent on hepatic cholesterol synthesis. PMID- 1905633 TI - Predictability of low-density lipoprotein levels during apheretic treatment of hypercholesterolaemia. AB - The efficiency and efficacy of low-density lipoprotein (LDL) apheresis performed with a dextran sulphate cellulose (DSC) regenerating unit were tested in five familial hypercholesterolaemic patients. LDL apheresis was repeated four times at both bi-weekly and weekly intervals, processing one plasma volume each time. The efficiency of the procedure (i.e., the extent of lipoprotein removal) was nearly identical with both schedules. Efficacy parameters, i.e., decreases of plasma total and LDL cholesterol (TC and LDL-C) and apo B, were highly correlated (r greater than 0.96) with preapheresis levels, allowing an accurate prediction of the absolute lipid removal in the single individual. Plasma triglycerides, high density lipoprotein cholesterol, apo A-I and apo A-II recovered rather rapidly, reaching 91-96% of the pre-apheresis values in 48 hours; the recovery of TC, LDL C and apo B was much slower, with a relatively rapid early phase (80% recovery after about 7 days) followed by a successive slower rise. This pattern was highly reproducible in the single patient, allowing the definition of a simple mathematical model for an accurate (error less than 20%) prediction of the individual process. Based on this model one can design the treatment schedule necessary to maintain lipid levels within the desired range in the single individual. The hypolipidaemic efficacy of DSC apheresis appears, otherwise, not to be dependent upon the procedure per se, but on other individual factors, e.g. the amount of removable lipoproteins and the rate of lipid recovery; both can be predicted with sufficient accuracy. PMID- 1905634 TI - Sodium lithium countertransport is acutely influenced by heparin-induced extracorporal LDL precipitation. AB - Sodium lithium countertransport may be a genetic marker for arterial hypertension and for the risk of diabetic nephropathy in type 1 diabetic patients. Since various factors seem to influence the transport velocity including serum lipid alterations, erythrocytes of seven patients with severe hyperlipoproteinaemia who were chronically and intermittently treated with LDL apheresis were examined before and immediately after therapy. The LDL apheresis reduced sodium lithium countertransport significantly (0.383 vs 0.269, P less than 0.02). Therefore, we conclude that serum lipid composition must be considered when interpreting sodium lithium countertransport velocity. PMID- 1905635 TI - Modulation of neutrophil and monocyte function by recombinant human granulocyte macrophage colony-stimulating factor in patients with lymphoma. AB - Granulocyte macrophage colony-stimulating factor (GM-CSF) has been shown to inhibit the chemotaxis and enhance the oxidative burst response of human neutrophils in vitro. The present study describes the effect of recombinant GM CSF on the neutrophil and monocyte function in patients with lymphoma undergoing GM-CSF treatment. Patients with either Hodgkin's or non-Hodgkin's lymphoma were treated with various dosages (2-16 micrograms kg-1 body weight per day for 5 days) of rhGM-CSF by intravenous or subcutaneous route. Prior to and on day 5 of rhGM-CSF treatment, neutrophil and monocyte chemotaxis and chemiluminescence responses to f-Met-Leu-Phe, zymosan activated serum (ZAS) and opsonized zymosan (OZ) were determined. It was observed that chemotactic response of neutrophils to f-Met-Leu-Phe and ZAS was reduced, whereas the chemiluminescence response of both cell types to f-Met-Leu-Phe and zymosan was enhanced by up to 43-fold. rhGM-CSF treatment did not affect degranulation of the neutrophils as measured by release of vitamin B12 binding protein. Degree of modulation of neutrophil and monocyte function by rhGM-CSF was independent of rhGM-CSF dosages administered. These data suggest that phagocytic defence system may be enhanced by GM-CSF treatment and that this cytokine may be a useful therapeutic adjunct in compromised patients. PMID- 1905636 TI - Identification of a new mutation responsible for hepatoerythropoietic porphyria. AB - A deficiency in the activity of uroporphyrinogen decarboxylase (URO-D), the fifth enzyme of the haem biosynthetic pathway, is found in two hereditary diseases, familial porphyria cutanea tarda (PCT) and hepatoerythropoietic porphyria (HEP). Little is known about the genetic relationship between those two diseases and it has been postulated that HEP is the homozygous form of PCT. A URO-D cDNA was cloned from an HEP patient and the comparison between the mutant and the wild type sequences showed a single base difference within the coding sequence leading to the replacement of a glutamic acid by a lysine at codon 167 of the mutant protein. This replacement produced a protein which is rapidly degraded in the presence of cell lysate. On the basis of hybridization of synthetic oligomers to amplified genomic DNA, we demonstrated that this patient is homozygous for this single base mutation. In order to look for any relationship between HEP and PCT, we tested six unrelated patients with familial PCT and could not detect the codon 167 mutation in any of them. These results indicate an heterogeneity in the mutations responsible for the PCT and HEP phenotypes. PMID- 1905637 TI - Fish oil reduces ethanol-induced damage of the duodenal mucosa in humans. AB - Eight healthy volunteers were studied before and after 3 weeks of dietary supplementation with fish oil (10.5 g day-1, 18% (1.9 g) eicosapentaenoic acid). Duodenal mucosal lesions were induced by instillation of 40 ml ethanol (40%). Mean endoscopic lesion score was lower after fish oil treatment (1.62 +/- 0.32; mean +/- SEM) than before (3.25 +/- 0.31; P less than 0.01). Histologic lesion score fell from 22.75 +/- 1.98 before treatment to 13.50 +/- 1.51 after fish oil (P less than 0.01). Basal and pentagastrin-stimulated gastric acid output remained unaffected. Release of prostaglandin E2, 6-keto-prostaglandin F1 alpha, and thromboxane B2 from biopsy specimens of the duodenal mucosa in vitro was not significantly altered after fish oil ingestion. In the same in vitro system calcium ionophore A23187-induced release of total leukotriene C (LTC) increased from 10.6 +/- 1.5 ng g-1 mucosa 20 min before treatment to 30.4 +/- 3.2 ng after fish oil. High pressure liquid chromatography analysis showed that this increase was partly due to formation of LTC5 as after fish oil 28% of total LTC were identified as LTC5 whereas 72% were LTC4. We conclude that in humans fish oil reduces ethanol-induced damage of the duodenal mucosa without inhibiting gastric acid secretion or stimulating prostaglandin formation. It remains to be clarified if the changes in leukotriene formation are relevant for the mucosaprotective fish oil effect. PMID- 1905638 TI - Plasma noradrenaline in cirrhosis: a study of kinetics and temporal relationship to ascites formation. AB - The kinetics of plasma noradrenaline (NA) were studied in 14 patients with cirrhosis and ascites and 13 normal subjects. [3H]noradrenaline ([3H] NA) was infused intravenously to steady state and the spillover of NA into plasma and its clearance from plasma calculated. The increase in plasma NA in the cirrhotic patients was due to an increase in NA spillover (14.5 vs 3.9 nmol min-1m-2; P less than 0.001). NA plasma clearance was also increased in the cirrhotic patients (3.5 vs 2.11 min-1m-2; P less than 0.01). Plasma NA and dihydroxyphenylglycol (DHPG), a metabolite of NA of which a portion is formed after re-uptake of NA into sympathetic nerve endings, were then measured in 23 patients with cirrhosis and ascites, 17 patients with cirrhosis who had never had ascites, and 34 normal subjects. Both plasma NA and DHPG were significantly increased in the patients with ascites (NA 4.7, DHPG 14.7 nmol l-1 and in the patients with cirrhosis but no ascites (NA 3.8, DHPG 12.0 nmol l-1) compared with normal subjects (NA 1.9, DHPG 8.8 nmol 1-1). Therefore, the increase in plasma NA in cirrhosis is due to increased activity of the sympathetic nervous system rather than interference with the metabolism of NA or impaired neuronal uptake of NA. This increase appears to precede the development of ascites. PMID- 1905640 TI - Mechanisms of protein conservation during xylitol infusion after burn injury in rats: isotope kinetics and indirect calorimetry. AB - In order to study the mechanisms by which nutrients influence post-trauma metabolism, Sprague-Dawley rats received a 25% full-thickness burn and were randomly assigned to receive 12.5 g kg-1 bodyweight (BW) per day amino acids (AA) only, AA and 14.7 g hydrous glucose kg-1 BW per day or AA and 14.7 g hydrous xylitol kg-1 BW per day. After 4 days of hypocaloric feeding, rats receiving xylitol had a cumulative nitrogen balance of +213 +/- 82 mg N, which was significantly (P less than 0.001) better compared with either the AA with only 493 +/- 61 mg N or the AA and glucose group (P less than 0.01) with -160 +/- 101 mg N. During glucose infusion reduction of insulin-mediated fat oxidation was partially compensated by an increase in glucose oxidation. Xylitol infusions resulted in increased glucose oxidation compared with the amino acid only group without simultaneously reduced fat oxidation. Although glucose and xylitol are calorically similar, their protein sparing properties and metabolic action after injury cannot be based entirely upon their caloric equivalent. PMID- 1905639 TI - Hereditary hepatic porphyria due to homozygous delta-aminolevulinic acid dehydratase deficiency: studies in lymphocytes and erythrocytes. AB - Activities of delta-aminolevulinic acid (ALA) dehydratase and porphobilinogen (PBG) deaminase, and haem content were determined in EB-virus transformed lymphocytes from two patients with homozygous ALA dehydratase deficiency, and their family members to determine the expression of the specific gene defect in this cell type. ALA dehydratase activity, but not PBG deaminase activity or haem content, was markedly decreased in lymphocyte preparations from both patients with homozygous enzyme deficiency, and moderately decreased in subjects heterozygous for enzyme deficiency. Immunochemical quantitation of erythrocyte ALA dehydratase suggested the presence of a cross-reactive material in a patient with a late-onset of acute hepatic porphyria due to the homozygous enzyme deficiency. PMID- 1905642 TI - Cytokine interactions in experimental cutaneous leishmaniasis. II. Endogenous tumor necrosis factor-alpha production by macrophages is induced by the synergistic action of interferon (IFN)-gamma and interleukin (IL) 4 and accounts for the antiparasitic effect mediated by IFN-gamma and IL 4. AB - Tumor necrosis factor-alpha (TNF-alpha) strongly activates murine peritoneal macrophages (M phi) for killing of amastigotes from Leishmania major in the presence of low amounts of interferon-gamma (IFN-gamma). Recently, we found that IFN-gamma and interleukin 4 (IL 4) also synergistically enhance the antileishmanial potential of M phi. In this report, evidence is provided that the synergism of IFN-gamma and IL 4 is based on the ability of the lymphokines to induce the endogenous production of TNF-alpha. First, both IFN-gamma and IL 4 as single agents and in combination were potent inducers of TNF-alpha production by M phi infected with L. major amastigotes. Second, the synergistic effect of IFN gamma and IL 4 on parasite killing by M phi strongly correlated with their synergistic effect on the release of TNF-alpha. Third, the IFN-gamma/IL 4 mediated parasite elimination was completely abrogated not only in the presence of antibodies to IFN-gamma and IL 4, but also with an antibody specific for TNF alpha. Consistent with the conclusion that endogenously produced TNF-alpha accounts for the synergism of IL 4 with IFN-gamma is the finding that N omega monomethyl-L-arginine, an inhibitor of the L-arginine-dependent generation of microbicidal nitrogen intermediates, totally blocked the M phi activation induced by IFN-gamma combined with IL 4 as well as by IFN-gamma combined with TNF-alpha. These results underline the complex interplay of cytokines derived from lymphocytes and M phi and the role of TNF-alpha as pivotal factor for the induction of antileishmanial effector functions. PMID- 1905641 TI - Fluvoxamine-tricyclic antidepressant interaction. An accidental finding. PMID- 1905643 TI - Interleukin 4 induces CD8 alpha expression on T cell receptor V gamma 5 thymocytes. AB - It is generally accepted that most T cell receptor (TcR) gamma/delta cells are CD4-CD8-. After in vitro culture; however, a low percentage of these cells express the CD8 alpha subunit. We show here that addition of recombinant interleukin (IL) 4 to IL 2-cultured murine TcR V gamma 5 thymocytes induces the expression of CD8 alpha; CD8 beta is not expressed. Co-addition of the anti-IL 4 mAb 11B11 abrogates the induction of CD8 alpha expression, ruling out the possibility of a contaminant. Furthermore, we demonstrate that a substantial part of freshly prepared TcR V gamma 5 thymocytes express CD8 alpha. PMID- 1905644 TI - Fracture healing induces expression of the proto-oncogene c-fos in vivo. Possible involvement of the Fos protein in osteoblastic differentiation. AB - Here we report marked in vivo expression of the c-fos gene in the external soft callus (ESC) and periosteal hard callus (PHC) at the fracture site of adult rat tibia. Northern-blot analysis showed that the ESC expressed a high level of c-fos mRNA from post-fracture day 10 to day 28, the time when endochondral ossification progressed, and that the ossifying PHC also expressed c-fos mRNA. This c-fos expression was followed by sequential expression of the genes for alkaline phosphatase, osteopontin and osteocalcin, which are osteoblastic markers. Immunohistochemical analysis showed that the c-Fos protein was predominantly located in osteoblasts in the ossifying calluses. PMID- 1905645 TI - Reactivation of metal-requiring apoenzymes by phytochelatin-metal complexes. AB - The enzymatically inactive, metal-requiring apoforms of diamino oxidase and of carbonic anhydrase were reactivated by copper-and zinc-phytochelatin complexes, respectively. The level and the rate of reactivation effected by metal complexes consisting of poly(gamma-glutamylcysteinyl)glycine as well as by the respective free metal ion were compared. An efficient transfer of zinc and copper from phytochelatin-complexes to apoenzymes was observed in vitro. PMID- 1905646 TI - Subcellular distribution of enzymes involved in the biosynthesis of cyanelle murein in the protist Cyanophora paradoxa. AB - Cyanelle containing organisms, notably Cyanophora paradoxa, the best studied among them, are unique with respect to the occurrence of peptidoglycan (murein) within an eukaryotic cell. Enzyme activities involved in the biosynthesis of UDP N-acetyl-muramylpentapeptide could be localized within the cyanelle compartment. Some of the enzymes performing later steps of murein biosynthesis were detected in the postcyanelle supernatant rather than in the cyanelle lysate. This is taken to reflect a 'periplasmic' location of these enzymes that are partially liberated upon rupture of the cyanelle outer membrane. PMID- 1905647 TI - Atropine dissociates complexes of muscarinic acetylcholine receptor and guanine nucleotide-binding protein in heart membranes. AB - Complexes of muscarinic acetylcholine receptor and guanine nucleotide-binding protein (G protein) are formed in the presence of the agonist carbachol. The complexes remain stable after removal of agonist, and survive subsequent solubilization from cardiac membranes and purification. Dissociation of the receptor from the G protein occurs when the antagonist atropine is added following removal of agonist. This is the first direct demonstration of destabilization of receptor-G protein complexes by the binding of an antagonist. PMID- 1905648 TI - Talin binds to actin and promotes filament nucleation. AB - Platelet talin binds to actin in vitro and hence is an actin binding protein. By four different non-interfering assay conditions (fluorescence, fluorescence recovery after photobleaching, (FRAP), dynamic light scattering and DNase-I inhibition) we show that talin promotes filament nucleation, raises the filament number concentration and increases the net rate of actin polymerization but has no inhibitory effect on filament elongation. Binding of talin to actin occurs at a maximal molar ratio of 1:3 as determined by fluorescencetitration under G buffer conditions. The overall binding constant was approximately 0.25 microM. PMID- 1905649 TI - On the mechanism of rotenone-insensitive reduction of quinones by mitochondrial NADH:ubiquinone reductase. The high affinity binding of NAD+ and NADH to the reduced enzyme form. AB - NADH acts as an incomplete competitive inhibitor for 5,8-dioxy-1,4-naphtoquinone during its rotenone-insensitive reduction by mitochondrial NADH:ubiquinone reductase. NAD+ and ADP-ribose act as incomplete mixed-type inhibitors. Ki of NAD+ and NADH towards quinone are about one order less than towards ferricyanide. The bimolecular rate constant of the reduction of the enzyme by NADH in the quinone reductase reaction is about 2 times less than that of ferricyanide reductase reaction. These data indicate that the reduction site of 5,8-dioxy-1,4 naphtoquinone is close to NAD+/NADH and ferricyanide binding site. It seems that during the steady-state reduction of ferricyanide and 5,8-dioxy-1,4-naphtoquinone these oxidizers react with NADH:ubiquinone reductase reduced to different extents. PMID- 1905650 TI - Metaphase chromosomes from mammalian cells stimulate fusion of artificial phospholipid vesicles. AB - Isolated mitotic chromosomes are able to form complexes with phosphatidylcholine liposomes in the presence and absence of Ca2+ ions, in the latter case in the presence of polyamines. Interactions with chromosomes stimulates liposome fusion. The fusion is promoted by condensed and EDTA-decondensed chromosomes. PMID- 1905651 TI - Rat platelets are deficient in internal Ca2+ release and require influx of extracellular Ca2+ for activation. AB - Calcium fluxes were studied in fura-2-labeled rat platelets. Thrombin, ADP and ionomycin induced rapid mobilization of internally stored Ca2+, which resulted in only a moderate increase of cytosolic [Ca2+]i. Thrombin and ADP stimulated influx of extracellular Ca2+, which was monitored as uptake of 45Ca2+ and of Mn2+. With either agonist, the influx of Ca2+ magnified the initial increase of [Ca2+]i. Since responses of rat platelets were dependent on external [Ca2+], we conclude that Ca2+ influx complements the mobilization of internal stores to reach sufficiently high [Ca2+]i for full activation. A regulatory effect of protein kinase C modulators was observed on both agonist-induced elevation of [Ca2+]i and receptor-mediated Ca2+ entry. PMID- 1905652 TI - Critical care transport: aircraft and medicine. PMID- 1905653 TI - [Severe hypophosphatemia during cyclic enteral feeding]. PMID- 1905654 TI - Detection of neutral sugars in purified type G botulinum progenitor toxin and the effects of some glycolytic enzymes on its molecular dissociation and oral toxicity. AB - Arabinose and galactose were detected in purified type G botulinum toxin (Mr about 500,000) of Clostridium argentinense. The i.p. LD50/mg N of type G progenitor toxin was one-tenth, but the oral LD50/mg N twice that of type A-L toxin. The lysozyme-, endo-beta-galactosidase-, and N-glucanase-treated toxins each had a molecular mass of about 300,000. The oral toxicity of the endo-beta galactosidase or N-glucanase-treated toxin was one-fifth that of untreated progenitor toxin. On DEAE-Sephadex chromatography, the N-glucanase-treated toxin dissociated into two fractions, nontoxic and toxic. SDS-PAGE of the toxic fraction showed a single band with a Mr of about 150,000, and after dithiothreitol treatment, two bands with Mr of 100,000 and 50,000. PMID- 1905655 TI - Difficulties of molecular dissociation of Clostridium botulinum type G progenitor toxin. AB - Clostridium botulinum type G progenitor toxin was chromatographed on DEAE Sephadex and Q-Sepharose equilibrated with 0.05 M Tris-HCl buffer, pH 8.0, containing 0.2 M urea. The toxin was eluted in a single protein peak from DEAE Sephadex, but it was eluted in four protein peaks from Q-Sepharose; the third peak was toxic and the others were nontoxic. The third peak, appearing to be the toxic component, had a molecular mass of 150,000. In SDS-polyacrylamide gel electrophoresis, purified type G progenitor toxin migrated in six bands, with molecular masses of 150,000, 140,000, 58,000, 10,800, 10,600, and 10,400. Type G progenitor toxin may be composed of a toxin component with a molecular mass of 150,000 and a nontoxic component in a manner similar to progenitor toxins of other types. Type G toxic component, whether it was reduced or not, migrated in a single band to the same relative positions in SDS-PAGE; type A toxic component reduced with 2-mercaptoethanol migrated in two bands. PMID- 1905657 TI - Low copy number vectors for expression of fused genes to beta-galactosidase in Escherichia coli. AB - A series of six expression vectors, pXM184Lac.A, B, C, pXM184Z.A, B, C, based on the low copy plasmid pACYC184 that allow for expression of proteins fused to beta galactosidase in Escherichia coli is described. A level of 50,000 units of beta galactosidase is routinely observed and is easily identifiable on protein gels. This paper also reports the tight regulation of expression of the Trc promoter in these vectors using the LacIq repressor. PMID- 1905658 TI - Distinction between Clostridium botulinum type A strains associated with food borne botulism and those with infant botulism in Japan in intraintestinal toxin production in infant mice and some other properties. AB - Two strains of Clostridium botulinum type A associated with food-borne botulism and six strains associated with infant botulism in Japan were compared in intraintestinal toxin production in infant mice, in vitro toxin and hemagglutinin production, molecular sizes of the toxins, and some other properties. The infant botulism-associated strains, producing M toxin (Mr 300 kDa) but no hemagglutinin, showed significantly lower 50% infective doses in infant mouse intestines. The antigenicities of the toxin differed between the two groups, while the biochemical properties of the cultures did not. Besides infant botulism associated strains, this set of properties were found only in a strain isolated from honey of South American origin. PMID- 1905656 TI - Identity of hemolysins produced by Bacillus thuringiensis and Bacillus cereus. AB - A hemolysin (Bt-hemolysin) produced by Bacillus thuringiensis var. kurstaki HD-1 producing crystalline toxin(s) was purified by successive treatments of ammonium sulfate (45-65%) and column chromatography using DEAE-cellulose, Sephadex G-75 and KB-002 (a hydroxyapatite column for fast protein liquid chromatography). A hemolysin (Bc-hemolysin) produced by B. cereus HG-6A was also purified by the same procedure. The purified Bt-hemolysin and Bc-hemolysin, both of which are thiol-activated hemolysins, were biologically, physicochemically and immunologically identical. These findings provide further evidence of the similarity of B. thuringiensis, which is being used as a biological insecticide, to B. cereus, a toxigenic organism of food poisoning. PMID- 1905659 TI - Genetic transformation of various species of Enterococcus by electroporation. AB - A transformation system for Enterococcus faecalis was developed which uses untreated (i.e., non-protoplasted) cells and the electroporation technique. The optimized protocol resulted in transformation efficiencies of up to 4 x 10(6) transformants per microgram of plasmid DNA. All strains of E. faecalis tested could be transformed by this method, albeit with differing transformation efficiencies. Using the protocol optimized for E. faecalis we successfully transformed Enterococcus faecium, E. hirae, E. malodoratus and E. mundtii. PMID- 1905662 TI - The response to artificial selection from new mutations in Drosophila melanogaster. AB - Twenty generations of divergent selection for abdominal bristle number were carried out starting from a completely homozygous population of Drosophila melanogaster. All lines were selected with the same proportion (20%) but at two different numbers of selected parents of each sex (5 or 25). A significant response to selection was detected in eight lines (out of 40) and, in most cases, it could be wholly attributed to a single mutation of relatively large effect (0.5-2 phenotypic standard deviations). The ratio of new mutational variance to environmental variance was estimated to be (0.33 +/- 0.11) X 10(-3). The distribution of mutant effects was asymmetrical, both with respect to bristle number (85% of it was negative) and to fitness (most detected bristle mutations were lethal or semilethal). Moreover, this distribution was leptokurtic, due to the presence of major genes. Gene action on bristles ranged from additive to completely recessive, no epistatic interactions being found. In agreement with theory, larger responses in each direction were achieved by those lines selected at greater effective population sizes. Furthermore, the observed divergence between lines selected in opposite directions was proportional to their effective size, as predicted for mutations of large effect. PMID- 1905660 TI - Construction of scrA::lacZ gene fusions to investigate regulation of the sucrose PTS of Streptococcus mutans. AB - The scrA gene coding for sucrose EnzymeII of the phosphoenolpyruvate dependent phosphotransferase system previously isolated from Streptococcus mutans was fused in vitro to the promoterless lacZ' gene to monitor the expression of the scrA gene. The scrA::lacZ gene fusion was introduced back into S. mutans GS-5IS3 by two independent transformation procedures involving either linear or plasmid DNA to produce both scrA and scrA+ mutants. These mutants should prove useful for analyzing the regulation of sucrose transport in S. mutans. PMID- 1905661 TI - Molecular genetics of the Posterior sex combs/Suppressor 2 of zeste region of Drosophila: aberrant expression of the Suppressor 2 of zeste gene results in abnormal bristle development. AB - We report the molecular characterization of the Posterior sex combs-Suppressor 2 of zeste region of Drosophila melanogaster. The distal breakpoint of the Aristapedioid inversion divides the region into two parts. We have molecularly mapped the lesions associated with several loss of function mutations in the Polycomb group gene Posterior sex combs (Psc) proximal to this breakpoint. In addition, we have found that lesions associated with several loss of function mutations in the Suppressor 2 of zeste [Su(z)2] gene lie distal to this breakpoint. Since the breakpoint does not cause a loss of function in either gene, no essential sequences are shared by these two neighboring genes. There are three dominant gain of function mutations in the region that result in abnormal bristle development. We find that all three juxtapose foreign DNA sequences upstream of the Su(z)2 gene, and that at least two of these mutations (Arp1 and vgD) behave genetically as gain of function mutations in Su(z)2. Northern and in situ hybridization analyses show that the mutations result in increased accumulation of the Su(z)2 mRNA, which we argue is responsible for the bristle loss phenotype. PMID- 1905663 TI - Successful prevention of local and cutaneous hypersensitivity reactions to seminal fluid with intravaginal cromolyn. AB - Seminal fluid hypersensitivity usually is characterized by postcoital vulvovaginal itching, swelling, redness, with or without systemic signs and symptoms. Efforts to manage this condition have either met with poor patient acceptance or have not been uniformly successful. We describe a 23-year-old atopic woman with documented IgE-mediated local and cutaneous hypersensitivity to SF. Using a controlled, single-blind challenge method, pretreatment with intravaginal 4% cromolyn sodium in a water-based cream completely blocked both local and cutaneous immediate hypersensitivity reactions to SF in this highly sensitive patient. We believe this may represent an alternative and more desirable method of preventive management in such patients. PMID- 1905664 TI - Transcription of the Bacillus subtilis spoIIA locus. AB - The spoIIA operon encodes three genes, including the structural gene for a sporulation-induced sigma factor sigma F. We used deletion analysis of spoIIA lacZ fusions to define the location of the spoIIA promoter. We found that sigma H RNA polymerase transcribes spoIIA accurately in vitro and propose that sigma H directs transcription of spoIIA during sporulation. PMID- 1905665 TI - Cloning and nucleotide sequence of the major capsid protein from Lactococcus lactis ssp. cremoris bacteriophage F4-1. AB - The gene (mcp) coding for the major capsid protein (MCP) of the Lactococcus lactis ssp. cremoris bacteriophage F4-1 has been cloned and its nucleotide sequence determined. The mcp gene was localized, by Western blotting with rabbit antiserum against intact bacteriophage, within a 3.3-kb HindIII-Spe I fragment and the sequence of the entire region determined. The 35-kDa MCP is coded for by a 905-bp open reading frame preceded by a putative ribosome-binding site. Deletion analysis and N-terminal sequencing of the MCP confirmed the identification of the gene coding for this bacteriophage MCP. PMID- 1905666 TI - An SfiI restriction map of the Bacillus subtilis 168 genome. AB - A restriction map of 24 SfiI (GGCCN4/NGGCC) restriction fragments has been constructed for the Bacillus subtilis genome. The combined sizes of the fragments indicate a genome size of approx. 4.2 Mb. The SfiI fragments range in size from 7 730 kb. Genetic markers have been located on 19 of the SfiI fragments, and 69 genetic markers have been assigned to the SfiI restriction map. PMID- 1905667 TI - Gene-protein relationships in the flagellar hook-basal body complex of Bacillus subtilis: sequences of the flgB, flgC, flgG, fliE and fliF genes. AB - The nucleotide sequence of five genes from the major Bacillus subtilis chemotaxis locus has been determined. Four of these genes encode proteins that are homologous to the Salmonella typhimurium FlgB, FlgC, FlgG and FliF proteins. One gene encodes a protein that is homologous to the Escherichia coli FliE protein. The data from S. typhimurium and E. coli suggest that all of these proteins form part of the hook-basal body (HBB) complex of the bacterial flagella. The FlgB, FlgC and FlgG proteins are components of the proximal and distal rods. The FliF protein forms the M-ring that anchors the rod assembly to the membrane. The role of the FliE protein within the HBB complex has not yet been determined. The similarity between the B. subtilis and S. typhimurium proteins suggests that the structure of the M-ring and the rod may be similar in the two species. However, we observed some differences in size and amino acid composition between some of the corresponding homologues that suggest the basal body proteins may be organized slightly differently within B. subtilis. PMID- 1905669 TI - Role of oxygen free radicals in respiratory distress induced by arachidonic acid in the rat. AB - The purpose of our present study is the possible implication of oxygen free radicals in the respiratory distress induced in rats by intravenous administration of arachidonic acid (20 mg/kg). The respiratory frequency was measured and plasma TXB2 concentration was assayed by RIA from blood withdrawn 1 min after arachidonic acid administration. The substances studied were: SOD, catalase, mannitol, DMSO, BHT, imidazole. All the drugs, except imidazole, significantly protect the rats from the respiratory distress induced by arachidonic acid. SOD, catalase, BHT and imidazole inhibit whereas mannitol and DMSO increase the plasma levels of TXB2. We suggest that oxygen free radicals generated in the respiratory burst induced by arachidonic acid are mainly responsible for the consequent respiratory distress. PMID- 1905668 TI - Polymers of Cu/Zn superoxide dismutase produced by cross-linking with glutaraldehyde. AB - Soluble polymers of bovine Cu/Zn superoxide dismutase (EC 1.15.1.1) have been prepared using the homobifunctional cross-linking reagent, glutaraldehyde. A form of the enzyme, a tetramer, with a molecular weight of 64,000 has been purified by gel filtration. The functional properties of the tetramer have been investigated. Reconstitution with copper and zinc was required for full activity. After metal reconstitution, the specific activity of the tetramer was shown to be close to 90% that of the native dimeric enzyme. The serum half-life of the tetramer in rats was found to be increased by a factor of six when compared with native superoxide dismutase. The tissue distribution of the two forms was also found to be different with the tetramer accumulating predominantly in the liver. PMID- 1905671 TI - Oxidative stress responses in the unicellular cyanobacterium Synechococcus PCC 7942. AB - Oxidative stress responses were tested in the unicellular cyanobacterium synechococcus PCC 7942 (R-2). Cells were exposed to hydrogen peroxide, cumene hydroperoxide and high light intensities. The extent and time course of oxidative stress were related to the activities of ascorbate peroxidase and catalase. Ascorbate peroxidase was found to be the major enzyme involved in the removal of hydrogen peroxide under the tested oxidative stress. Catalase activity was inhibited in cells, treated with high H2O2 concentrations, and was not induced under photooxidative stress. Catalase was specifically induced in cells treated with cumene hydroperoxide. Superoxide dismutase activity increased under conditions generating superoxide, such as high light intensities. The induction of the antioxidative enzymes was light dependent and was inhibited by chloramphenicol. PMID- 1905670 TI - MPP+ toxicity in E. coli under aerobic and anaerobic conditions. AB - MPP+ and paraquat (PQ+2) are two structurally analogous and highly toxic pyridinium compounds. The mechanism of PQ+2 toxicity is best understood in the bacterial model system. While numerous studies, in a variety of systems, have indicated the causative role of free radicals and other oxygen-derived active species in PQ+2 toxicity, this question is yet unresolved in the case of MPP+. In this study we have used the E. coli model and have demonstrated that MPP+ is toxic to bacterial cells in a dose and time dependent modes. Additionally, it is shown that only in the presence of molecular oxygen, bacterial inactivation occurred. The protective effects of the chemical scavenger--mannitol--and of histidine are presented. These results are in complete accord with a free radical mechanism for MPP+ toxicity. PMID- 1905672 TI - Enteral feeding as sole treatment for Crohn's disease: controlled trial of whole protein v amino acid based feed and a case study of dietary challenge. AB - A controlled trial was performed to compare enteral feeding with either an amino acid based feed or a whole protein feed as sole treatment for active Crohn's disease. Twenty four patients were studied (nine with ileal, 11 with ileocolonic, and four with colonic disease). Both feeds proved effective; nine of 13 patients randomised to receive the amino acid based feed were in clinical remission within three weeks as defined by a simple activity index compared with eight of 11 treated with the whole protein feed. Patients in clinical remission were then crossed over onto the other feed. None of the six patients who were changed to the whole protein feed relapsed over the subsequent three week period compared with three of seven patients who were changed to the amino acid based feed. In responders the median serum C reactive protein concentration fell from 21 mg/l (range 9-82) on entry to 6 mg/l (range 3-19) at six weeks. Seven patients relapsed within eight months of starting solid food (mean 3.7 months), while nine were still in remission (follow up period 3-9 months, median six months). Detailed studies of staged reintroduction of food and permitted food additives were carried out over a four year period in a patient with extensive stricturing small bowel Crohn's disease who had been brought into remission by open treatment with enteral feeding. Carrageenan, other permitted emulsifiers, bread, meat, potatoes, oranges, refined sugar, dairy produce, flour, and rice were all reintroduced without any objective ill effect, but green vegetables provoked a clinical and biochemical relapse within one week of introduction. Remission was rapidly achieved by switching back to the enteral feed but reintroduction of the low residue diet that had been previously tolerated produced a brisk relapse. Clinical and biochemical remission was again achieved by a return to the enteral feed but relapse again occurred with reintroduction of the low residue diet. These studies confirm the therapeutic effect of enteral feeding in Crohn's disease. This effect does not seem to be due to avoidance of whole protein, but the very low residue of chemically defined enteral feeds may be important, particularly in patients with intestinal strictures. PMID- 1905673 TI - The effects of high dietary concentrations of sodium saccharin on in vivo metabolism of xenobiotics in rats. AB - The effect of feeding a diet containing 7.5% sodium saccharin on the conjugation of [14C]phenol has been studied during neonatal development in male and female rats using a two-generation protocol. Decreased formation of phenol sulphate was observed in the F1 saccharin-treated rats from 4 wk of age and this was compensated for by an increase in the formation of quinol glucuronide. This shift in the conjugation pattern of [14C]phenol, with an increase in oxidation, was not sex specific. The daily excretion of indican was significantly increased from 5 wk of age. Feeding a diet containing 7.5% sodium saccharin did not affect in vitro activities of the enzymes involved in the conjugation reactions, that is, aryl sulphotransferase and uridine-5'-diphosphate glucuronyltransferase. The incorporation of 5% cysteine into the diet of saccharin-treated rats for 1 wk prevented the change in conjugation of [14C]phenol observed in the saccharin treated animals. Absorption of sodium [35S]sulphate from the gastro-intestinal tract was not appreciably affected by a high dietary concentration of sodium saccharin. A high dietary concentration of saccharin affected the conjugation of 3-hydroxyanthranilic acid during neonatal development, possibly as a result of sulphate depletion. PMID- 1905674 TI - Effect of cyclooxygenase inhibitor on excessive sputum. AB - Indomethacin suppository and aspirin inhalation reduced the amounts of sputum in the patients with bronchiectasis and chronic bronchitis. A 67-year-old woman with bronchiectasis received indomethacin suppository to relieve the lumbar pain. After the start of indomethacin, a reduction in the amount of sputum was observed and the volume of sputum returned to pretreatment levels after the cessation of indomethacin. Levels of cyclooxygenase products in the sputum during indomethacin was also much lower than their levels after discontinuance of indomethacin. A 64 year-old man with chronic bronchitis was also administered inhaled aspirin to control the sputum volume. Both indomethacin suppository and aspirin inhalation reduced the amounts of sputum. In addition to these cases, a 31-year-old woman with bronchial asthma was tried to control the sputum production with indomethacin, but it had no effect on the sputum volume. It is suggested that these drugs may be useful in the treatment of excessive sputum in bronchiectasis and chronic bronchitis. PMID- 1905675 TI - [Production of hydroxy and oxo fatty acids by microorganisms as a model of adipocere formation]. AB - Microbial synthesis of hydroxy and oxo fatty acids was studied as one of the model of experimental adipocere formation. Conversion of various fatty acids into 10-hydroxy and 10-oxo fatty acids by Micrococcus luteus was also studied. Fatty acids possessing cis-9-unsaturated forms were converted into 10-hydroxy and 10 oxo fatty acids. On the other hand, enoic acids possessing trans-9-unsaturated form or the ones which do not have double bond at the 9 -carbon position were inactive as substrates. 10-Hydroxypalmitic and 10-hydroxystearic acids were converted into the corresponding 10-oxo fatty acids but the 10-oxo fatty acids were inactive as substrates. To study the mechanism of the formation of 10 hydroxy and 10-oxo fatty acids, the crude enzyme preparation from Flavobacterium meningosepticum solubilized by sonication was used. The mechanism of hydration and dehydrogenation was proved by gas chromatography-mass spectrometry of 10 hydroxy and 10-oxo fatty acids produced from oleic acid in the presence of D2O or H218O. These results indicate that oleic acid is hydrated to 10-hydroxystearic acid at first and then, the latter compound is dehydrogenated to 10-oxostearic acid. PMID- 1905677 TI - Lawmakers target long-term care insurance reform. PMID- 1905676 TI - Assessing the elements of biopsychosocial functioning. AB - New findings are reported on the validity and reliability of an equation designed to predict the functional level of psychiatric patients. The equation employs measures of aggravating stress, biomedical impairment, coping skills, directive power, and environmental supports to predict level of functioning. A study of 95 subjects (38 patients and 57 nonpatients) found that the equation was able to discriminate significantly between psychiatric patients and persons with no history of psychiatric treatment and between the condition of long-term patients at different stages in treatment. The authors review findings from other studies that show the usefulness of the functional level equation in comparing patient groups, predicting prognosis and amount of treatment needed, improving functioning, and preventing disorder. PMID- 1905678 TI - [ADP ribosylation of actin--a cytotoxic principle of bacterial toxins]. AB - The ADP-ribosylation of actin is the pathobiochemical mechanism by which various clostridial toxins affect the eukaryotic target cell. The toxins are binary in structure and consist of a binding component and an enzyme component with ADP ribosyltransferase activity. Probably endocytosis-mediated the binding component transfers the clostridial ADP-ribosyltransferase into the target cell, whereupon G-actin but not F-actin is ADP-ribosylated. The ADP-ribosylated actin is incapable of polymerization but binds to the barbed ends of actin filaments to inhibit polymerization of non-modified actin. Thereby the ADP-ribosylation of actin destroys the cellular architecture of the microfilament network. The ADP ribosylating toxins are novel tools to study the physiological functions of actin. PMID- 1905679 TI - Human immunodeficiency resulting from a maturational arrest of germinal center B cells. AB - Common variable immunodeficiency (CVI) is an acquired human disorder involving a striking and heterogeneous maturational defect of B lymphocytes. In this study, we used a recently developed VH gene utilization assay to analyze the abundance of developmentally restricted and unrestricted V genes in blood B cells from nine CVI patients. Unrestricted clones (bearing rearranged VH5, VH4, or VH6 genes) were present in normal abundance in this group of CVI patients. However, clones bearing VH3L, a subgroup of the VH3 family normally abundant in blood B cells but absent in B cells at the germinal center stage, were deficient in seven of nine CVI patients. Based on these findings and a reconsideration of previously reported B cell features in CVI, we propose that the disorder represents in most cases a maturational arrest of B cells at the germinal center stage. PMID- 1905680 TI - Identification of cytokines which enhance (CSF-1, IL-3) or restrict (IFN-gamma) growth of intramacrophage Listeria monocytogenes. AB - Murine peritoneal macrophages were isolated by adherence and their listericidal activity assessed in the presence or absence of selected cytokines. Untreated macrophages were not highly listericidal, showing moderate killing in the first 2 h after infection, and allowed progressive microbial growth thereafter (up to 9 h). Pre-treatment of cells with 10 to 100 U/ml of IFN-gamma allowed macrophages to develop sustained listericidal activity for the 9-h observation period, with a 2-log reduction of Listeria CFU per monolayer. Pulsing of cells with TNF-alpha alone did not result in enhanced microbicidal activity but TNF-alpha potentiated IFN-gamma-induced listericidal activity, resulting in high levels of killing when both cytokines were present. Conversely, macrophages pre-treated with interleukin 3 (IL-3) or colony-stimulating factor-1 (CSF-1) were found to be much more permissive for Listeria growth. Neither IL-3 nor CSF-1 abrogated IFN-gamma induced listericidal activity. Moreover, neither IL-3 nor CSF-1 had any effect on the ability of macrophages to develop a respiratory burst following Listeria infection, as judged by H2O2 release following in vitro infection. Overall, these results suggest that different cytokines may have opposing effects on intracellular microbial growth, and that the balance of cytokine production in vivo may determine the resistance or susceptibility of the infected host. PMID- 1905681 TI - Implications of a mental health intervention for elderly mentally ill residents of residential care facilities. AB - Unresolved issues of responsibility between mental health and aging systems low priority within the mental health system for serving older RCF residents, and little expectation for the facility to be a treatment environment, all contribute to gaps in service delivery to mentally ill boarding home residents. This article reports the results of a two-year mental health intervention in RCFs. Findings show little intervention impact, but revealed that residents treated were generally socially marginal with weak ego skills, rather than significantly mentally ill. A more intensive program that restructures the facility's milieu to offer planned normal life demands and that models structured programs like milieu treatment, in situ treatment for the younger mentally ill, and programs for developmentally disabled persons is suggested. PMID- 1905682 TI - An in vitro technique to assess oxygenator potential for respiratory failure therapies. AB - To assess microporous membrane oxygenators (MMO) for long-term respiratory support, an in vitro test of 4 days duration has been developed. The objective is to screen oxygenators before they undergo expensive animal trials. As a sensitive indicator of performance change, CO2 transfer rates (VCO2) are determined with fresh bovine blood at the start, after 48 hours and after 96 hours of perfusion. Blood is used only for gas exchange evaluation and is replaced with plasma in the intervening periods. Data are obtained at blood flow rates (QB) of 1.0, 1.5 and 2.0 l/min for gas: blood flow ratios (QG:QB) of 2:1 and 5:1. The test has been conducted on Bentley BOS-CM50 oxygenators (n = 10). With heated dry air ventilation there was no significant change in VCO2 with time for all QB and QG:QB combinations. Plasma leakage did not occur into the gas compartment of the MMO. Similar results were obtained with heated humidified air ventilation. The findings are in agreement with existing animal studies of 4-7 days duration. PMID- 1905684 TI - Israel's expenditure on health services. PMID- 1905683 TI - An outbreak of penicillin-resistant Neisseria gonorrhoea in southern Israel. AB - Since the early 1980s the incidence of gonorrhea has been declining worldwide, as well as in Israel. This decline has been attributed to the fear of AIDS. We report an outbreak of penicillin-resistant Neisseria gonorrhoea that occurred in the last quarter of 1988 and throughout 1989 in southern Israel. During 1987 and the first three-quarters of 1988 only 13 new cases were diagnosed, all penicillin sensitive. During the epidemic, 94 new cases were diagnosed, 41% of them penicillin resistant. In March 1989, ceftriaxone was substituted for penicillin for the treatment of gonococcal urethritis. The number of cases of penicillin resistant gonorrhea dropped dramatically. It is concluded that despite the AIDS panic, outbreaks of gonorrhea can still be encountered, as demonstrated in this study. PMID- 1905685 TI - The single-hospital county: is its hospital at risk? AB - This article focuses on a hospital group that has not received adequate attention in the literature: the sole provider of short-term, acute hospital care located in a county. In Tennessee, SPHs (single provider hospitals) are fewer in number but are present in more counties than multiprovider hospitals (MPHs). They are smaller in size, less labor and capital intensive, more likely to be a government hospital, and more likely to be in a rural area with low income and limited health care resources. SPHs operate with lower costs, charge patients less, and have lower revenue write-offs than MPHs. As a result, their cash flow is sufficient to fund their depreciation and they consistently earn modest returns. Between 1982 and 1988, a total of 16 hospitals failed in Tennessee but only 3 were SPHs. While SPHs have not been profitable enough to make them ideal candidates for takeover by major hospital systems, they are not a population that is unduly at risk. PMID- 1905686 TI - Disaggregated annual health services expenditures: their predictability and role as predictors. AB - Risk-based capitation payments are among the fastest growing modes of reimbursement for health insurance. There is ongoing debate about whether the usual underwriting factors such as age and sex are sufficient for establishing annual premiums. This study examines the predictability of disaggregated annual services expenditures and their potential as predictors. The results show that outpatient services are generally more predictable than inpatient services. According to elasticity calculations, prior-year own-expenditures are the strongest predictors of annual expenditures. Of the own-expenditure elasticities, those pertaining to total and outpatient charges are the largest. Among prior year cross-expenditure elasticities, outpatient drug and outpatient office visit expenditures are the greatest. PMID- 1905689 TI - Locally advanced (noninflammatory) carcinoma of the breast: results and comparison of various treatment modalities. AB - From 1968-1987 237 women with Stage III, noninflammatory breast cancer were treated with various modalities. Ninety-three (39%) had Stage IIIA tumors, and 144 (61%) had Stage IIIB, noninflammatory tumors (AJC, 1983 staging). Median follow-up was 5.4 years (range 2 to 22 years). No patients were lost to follow up. Thirty-five patients (15%) were treated with irradiation alone, 27 (11%) with irradiation and adjuvant systemic therapy, 80 (34%) with mastectomy and irradiation, and 95 (40%) with combined mastectomy, irradiation, and systemic therapy. Local/regional control by treatment at 5 and 10 years, respectively, was 31% and 31% for irradiation alone, 47% and 47% for irradiation and systemic therapy, 80% and 80% for irradiation and mastectomy, and 93% and 78% for irradiation, mastectomy, and systemic therapy (p less than .0001). Actuarial disease-free survival by treatment was 19% and 12% for irradiation alone, 25% and 18% for irradiation and systemic therapy, 34% and 20% for irradiation and mastectomy, and 41% and 31% for irradiation, mastectomy, and systemic therapy, at 5 and 10 years, respectively (p = .0001). Patients given systemic therapy and/or irradiation prior to mastectomy had a better local/regional control and DFS and actuarial survival, although not achieving statistical significance (p = 0.10). Of the triple modality group of patients, there were no chest wall failures with chest wall doses greater than 5040 cGy (p = 0.3). There were 40/237 (17%) grade 2 or greater treatment sequelae. The administration of chemotherapy significantly increased complications. PMID- 1905688 TI - Cytoplasmic influence on the expression of nuclear genes affecting life span in Drosophila melanogaster. AB - In earlier studies we have found that the difference between short and long life spans of two inbred strains of Drosophila melanogaster is controlled by nuclear major genes. The present study has revealed a cytoplasmic factor that influences the expression of the nuclear longevity genes. The factor shows a typical maternal inheritance and is considered to be an extranuclear gene, such as mitochondrial DNA (chondriome). This paper marks the discovery of two basic forms of inheritance, nuclear and extra-nuclear, in the genetics of life span of D. melanogaster. These findings suggest that further studies, including genetic engineering, on longevity and aging might enable direct manipulation of these characters. PMID- 1905687 TI - Home health patient classification system. AB - A patient classification system has been developed for use in a home health setting. It is easy to use and is readily adaptable for computerization. The reliability and validity of the system has been supported through use by nurses on approximately 1,000 home visits. After appropriate adaptations are made, it can be a useful tool in measuring nurse workload and in costing out nursing services. PMID- 1905691 TI - Pericarditis and myocardial infarctions after Hodgkin's disease therapy. AB - From 1971 to 1984, 499 patients with all stages of Hodgkin's disease received mediastinal irradiation at the Institut Gustave-Roussy by 25 MV photons from a linear accelerator. Thirty-five pericarditis (10-year cumulative incidence rate of 9.5%) and 13 myocardial infarctions (MI) (10-year cumulative incidence rate of 3.9%) were observed. In contrast, no cases were diagnosed in a parallel series of 138 Hodgkin's disease patients treated without mediastinal irradiation during the same period of time (p less than 0.005 for pericarditis, p less than 0.05 for MI). By multivariate analysis, the role of total radiation dose given to the mediastinum and that of fraction size were evaluated, adjusting for age, sex, mediastinal involvement, and type of chemotherapy. The pericarditis risk was significantly increased with total dose greater than or equal to 41 Gy (relative risk (RR) = 3.25, p = 0.006) and with dose per fraction greater than or equal to 3.0 Gy (RR = 2.0, p = 0.06). The myocardial infarction risk was not found to be related to total dose nor to fraction size in this series, possibly because of the small number of events. PMID- 1905690 TI - Radiotherapy alone for medically inoperable carcinoma of the cervix: stage IA and carcinoma in situ. AB - The objective of this study was to define the role of radiotherapy alone for medically inoperable patients with Carcinoma in Situ (CIS) and Stage IA carcinoma of the uterine cervix. At the Mallinckrodt Institute of Radiology, Radiation Oncology Center from January 1959 through December 1986 21 patients with CIS and 34 with Stage IA were treated. All patients had histologically proven disease. The average age was 56 years for CIS and 51 years for Stage IA patients. Therapy for patients with CIS consisted of a single intracavitary insertion with a uterine tandem and colpostats. The average radiation doses were 4612 cGy to point A, 9541 cGy to the surface of the cervix, and 5123 milligram-hours (mgh). Radiotherapy for Stage IA tumors was delivered with intracavitary irradiation alone in 13 (average doses were 5571 cGy to point A, 10,430 cGy vaginal surface dose, and 6488 mgh). The other 21 patients were treated with external beam and intracavitary irradiation. The average whole pelvis dose was 1443 cGy with an additional 2354 cGy boost to the parametria with a midline stepwedge shield. The average intracavitary doses were 5200 cGy to point A, 10234 cGy to the vaginal surface, and 6293 mgh. None of the patients with CIS developed recurrent disease and none had severe sequelae of therapy. Only one patient with Stage IA developed recurrent disease in the pelvis. None developed metastatic disease. The severe complication rate was 5.9% (2/34) for Stage IA and only occurred in those receiving intracavitary irradiation and external beam irradiation. We conclude that irradiation consisting of intracavitary implants alone is excellent treatment for patients with medically inoperable Stage IA and CIS of the cervix. PMID- 1905692 TI - Possible underestimation of the incidence rate of prostate cancer in Japan. AB - We adjusted the prostate cancer incidence rate in Japan for differences between Japan and the US in the proportion of latent prostate carcinoma identified at autopsy and of localized tumors among all carcinomas of the prostate. The adjusted incidence rate of prostate cancer in Japanese in Japan by this method is estimated to be between 24.9 and 33.3 per 100,000 population, based on incidence rates from the population-based cancer registries of Miyagi, Japan, and Los Angeles and Hawaii, USA. The rate estimated here is almost 3-4 times greater than the rate reported previously. The difference in the incidence rates of prostate cancer between Japanese in Japan and the US (32.2-49.8 per 100,000) may therefore be substantially smaller than previously thought. PMID- 1905693 TI - Hereditary low level of plasma ceruloplasmin in LEC rats associated with spontaneous development of hepatitis and liver cancer. AB - Both young (5 weeks old) and old (61-100 weeks old) hereditary hepatitis LEC rats showed a markedly low level of plasma ceruloplasmin (Cp) ferroxidase activity as compared with that of age-matched LEA and BN strain rats. This trait was genetically examined by the use of (BN x LEC) F1 hybrid and (F1 x LEC) backcross rats. The F1 hybrids never developed hepatitis and showed a similar level of Cp to that found in the parental BN rats. Among the backcross rats with about 1:1 segregation rate for hepatitis, affected rats had a remarkably decreased level of Cp, as found in LEC rats, whereas unaffected rats exhibited a similar level of Cp to that of BN, F1 and LEA rats. These results indicate that the low level of Cp is heritable in a single autosomal recessive mode in LEC rats. The observed tight link between the low Cp level and the hepatitis in LEC rats suggests that defective copper metabolism may be associated with the occurrence of hepatitis in LEC rats, since Cp is a copper-binding protein primarily involved in copper transport from the liver. PMID- 1905694 TI - Abnormal copper accumulation in non-cancerous and cancerous liver tissues of LEC rats developing hereditary hepatitis and spontaneous hepatoma. AB - We studied the copper concentrations in the non-cancerous and cancerous liver tissues of LEC rats with hereditary hepatitis and spontaneous hepatoma by atomic absorption spectrophotometry. Copper concentration in the non-cancerous livers of 29-month-old male LEC rats was comparable to that in the livers of LEC rats aged 2, 3 and 8 months whose hepatic copper concentrations were more than 40 times those of normal LEA rats. Copper concentration in spontaneously developed hepatocellular carcinomas of the 29-month-old male LEC rats was lower than that in the surrounding non-cancerous liver tissues, but was still more than 39 times that of 8-month-old male LEA rats. These findings suggest that in LEC rats an abnormal copper metabolism may be maintained during the process of hepatic carcinogenesis. PMID- 1905695 TI - Serum requirement for in vitro invasion by tumor cells. AB - The effect of fetal calf serum (FCS) on in vitro invasion by rat ascites hepatoma cells (AH130) was studied by using the in vitro invasion assay. Although the coculture of the highly invasive clone (MM1) of AH130 cells and the mesothelial cell layer or endothelial cell layer in modified minimum essential medium supplemented with 10% FCS resulted in extensive penetration of the layer by the tumor cells, the omission of FCS resulted in an almost complete elimination of the in vitro invasion. The in vitro invasiveness by human small cell lung cancer cells (OC10) was also remarkably reduced by the omission of FCS from the assay medium, suggesting a requirement of serum for the in vitro tumor cell invasion. When 10% FCS was added to the medium 2 h after the tumor cell seeding in FCS-free invasion assay system, penetration by MM1 cells was observed within an hour. This rate of penetration was almost the same as that when 10% FCS was added at the time of tumor cell seeding. FCS was also required for the penetration of a mesothelial cell monolayer by MM1 cells in a defined growth medium (SFM-101), in which MM1 cells were well maintained. The invasion-inducing activity appears to be independent of the growth-stimulating activity in serum. PMID- 1905696 TI - Smoking habits and carcinoma of the stomach: a case-control study. AB - Over a period of 8 years, a case-control study was carried out on smoking habits in 117 patients with carcinoma of the stomach and 234 controls, and a significant association of a particular method of smoking with the site of gastric carcinoma was found in the cancer patients. Furthermore, there was a highly significant difference in method of smoking between the cancer patients and the control group. The prevalence of smoking habit in the latter was 37%, of which 26% had swallowed the smoke regularly. In contrast, the incidence of smoking habit in the cancer patients was over 56%, of which 64% had swallowed the tobacco smoke. The difference is highly significant (P less than 0.001). The study also suggests that the distal part, in particular, the antrum of the stomach was affected more frequently among the smokers of the cancer patients who had swallowed the smoke regularly but the cardiac end seemed to be involved more often in the other groups of the cancer patients. These included 'never-smokers,' ex-smokers and those smokers who did not swallow the smoke (P less than 0.01). It is therefore concluded that the swallowing of tobacco smoke seems to influence the site of gastric carcinoma. The relative risk was six-fold higher among the smokers who did swallow the smoke compared with the 'never-smokers' of the control group. PMID- 1905698 TI - Induction of transplantable tumors by repeated subcutaneous injections of natural and synthetic vitamin E in mice and rats. AB - Natural vitamin E and synthetic vitamin E (dl-alpha-tocopheryl acetate) were tested for their tumorigenicity in rodents. Transplantable tumors, at the site of injection, were induced by repeated injections of these compounds in two strains of mice, NFS/N and C57BL/6N x C3H/He F1, and in a strain of rats, Fischer 344. Natural vitamin E was tumorigenic in both strains of female mice only when injected with soya oil. In contrast, dl-alpha-tocopheryl acetate alone was capable of inducing tumors in Fischer 344 rats. Only one out of 5 male NFS/N mice given dl-alpha-tocopheryl acetate developed a tumor. Therefore, Fischer 344 rats were more susceptible to tumor formation by dl-alpha-tocopheryl acetate than NFS/N mice. dl-alpha-Tocopheryl acetate with soya oil or with palm oil also resulted in the formation of transplantable tumors in NFS/N mice and Fischer 344 rats. There was no difference in the tumor incidence between mice treated with dl alpha-tocopheryl acetate alone and dl-alpha-tocopheryl acetate plus soya oil or palm oil. However, in rats, the incidence was lower for a group treated with dl alpha-tocopheryl acetate plus palm oil than for those with dl-alpha-tocopheryl acetate alone and with dl-alpha-tocopheryl acetate plus soya oil. PMID- 1905697 TI - Different effects of carbon tetrachloride on carcinogen-induced hepatocellular carcinoma and normal liver of the rat: lowered lipid peroxidation and accelerated necrosis in cancer. AB - To investigate molecular responses to lipid peroxidative stimuli in neoplastic cells, lipid peroxidation was induced in liver of rats bearing 3'-methyl-4 dimethylaminoazobenzene-induced hepatocellular carcinoma by injecting a high dose of carbon tetrachloride (CCl4), a strong lipoperoxidative reagent. Normal rat livers with or without CCl4 treatment served as controls. CCl4 administration markedly provoked fatty metamorphosis, visualized by oil red O staining, in normal livers while minimal fatty changes were seen in hepatocellular carcinomas, where necrosis was often observed instead. After CCl4 treatment, the thiobarbituric acid values (representing levels of lipid peroxides in the tissue) were increased two-fold in the untreated normal liver, but were unchanged in the cancer tissue. Levels of vitamin C, an acutely reactive antioxidant, measured by high-performance liquid chromatography were not influenced by the CCl4 injection in the cancer tissue whereas a significant decrease was evident in normal livers. The total fatty acid content, measured by gas chromatography, was significantly lower in the cancer tissue than in the normal liver while the ratio of polyunsaturated fatty acids (PUFAs) in total fatty acids was little changed. Resistance of hepatocellular cancer cells to fatty metamorphosis and their susceptibility to necrosis induced by free radicals may be due to the paucity of the target PUFAs in their cell membrane fraction, resulting in low levels of lipid peroxides. Peroxidation of PUFAs might act as a "shock absorber" against free radical-induced toxic cell death in normal cells. PMID- 1905699 TI - Promotion of BALB/3T3 cell transformation by the okadaic acid class of tumor promoters, okadaic acid and dinophysistoxin-1. AB - Okadaic acid and dinophysistoxin-1 are non-12-O-tetradecanoylphorbol-13-acetate (non-TPA)-type tumor promoters, which enhance chemically induced tumorigenesis on mouse skin through a different mechanism from that of TPA. In the present study, we examined the promoting effects of these okadaic acid class tumor promoters on a two-stage transformation using BALB/3T3 cells which was designed to simulate in vivo two-stage carcinogenesis. Cells were treated first with a low dose of the initiator 3-methylcholanthrene (MCA) and then with a test chemical. Okadaic acid and dinophysistoxin-1 significantly enhanced the MCA-induced cell transformation. Okadaic acid tetramethyl ether, an inactive compound, did not affect the transformation of MCA-treated cells. The okadaic acid class of tumor promoters failed to induce transformation without pretreatment by MCA. Okadaic acid did not show initiating activity in the two-stage transformation assay in which cells were treated first with okadaic acid and then with TPA. These results indicate that this transformation assay with BALB/3T3 cells is useful to predict tumor promoting activity of non-TPA-type as well as TPA-type tumor promoters, before long-term in vivo two-stage carcinogenesis experiments are carried out. PMID- 1905700 TI - Alteration of physiological activity of activated macrophages through L-arginine metabolism. AB - Our aim in this study was to define the effect of L-arginine on macrophages (M phi) in relation to the decay of tumoricidal activity of activated M phi. We found that the activated M phi retained their cytotoxicity when cultured in L arginine-deficient medium but not in conventional medium. Such a decline of tumoricidal activity was associated with increase of glucose consumption and concomitant lactate production, resulting in M phi death. Addition of glucose to the culture medium of activated M phi appeared to cause only a slight delay of the decrease of tumoricidal activity and M phi death. These events were also coincident with a decrease of electron transport activity in mitochondria. Cytological observation by electron microscopy clearly showed the structural alteration or destruction of mitochondria, which preceded the changes of other physiological and functional activities. These results demonstrate that the L arginine-dependent cytolytic activity against tumor target cells also impairs M phi functions and ultimately induces M phi death, which is primarily mediated by the inhibition of mitochondrial activity. PMID- 1905701 TI - Effects of lactogenic hormones on morphological development and growth of human breast epithelial cells cultivated in collagen gels. AB - We investigated the hormonal dependence of the growth and morphological development of human breast epithelial cells (HBEC) cultivated in collagen gels floating on serum-free medium. HBEC used had grown out from breast carcinoma tissue and from histologically non-malignant tissue fragments in the same mastectomy specimens. In the presence of all three lactogenic hormones, hydrocortisone (HC), insulin (INS), and prolactin (PRL), both carcinoma-derived and histologically non-malignant tissue-derived HBEC grew and formed cell masses with protruding tubule-like extensions that consisted of a multilayer of cells. Deletion of any one of the hormones from the medium had no effect on cell growth of HBEC derived from either tissue type. However, morphological development, especially the morphology of the tubule-like extensions, was altered in the histologically non-malignant tissue-derived HBEC by deletion of HC or INS, and by deletion of HC, but not INS, in the carcinoma-derived HBEC. The present results suggest that the carcinoma-derived HBEC have decreased responsiveness to INS as compared to that of HBEC derived from histologically non-malignant breast tissue. PMID- 1905702 TI - Immunohistochemical expression of blood group substances and related carbohydrate antigens in breast carcinoma. AB - In forty-one carcinomas and sixteen benign lesions (fibroadenoma and mastopathy) of the human breast, immunohistochemical expression of sialylated and non sialylated forms of both Lea and Lex, and the A, B, and H type 2 blood group substances were studied by using an indirect immunoperoxidase staining. In normal ductal epithelium and benign lesion of breast, Lewis-related antigens were mostly expressed. Breast carcinomas showed these antigens with the following frequencies: Lea, 31.7% (13/41); sialyl Lea, 56.1% (23/41); Lex, 46.3% (19/41); sialyl Lex, 68.3% (28/41); A/B/H type 2, 38.1% (16/41). Sialylated forms of Lea and Lex were observed more frequently than their respective non-sialylated forms in breast carcinomas. In both one normal epithelium and four carcinomas of breast with Le(a-b-) phenotype, the expressions of type 2 antigens were observed, while type 1 antigens were not consistently expressed. Although compatible expression was observed in all specimens of both normal epithelium and benign lesion of breast, twenty-four cases with the deletion of A and/or B antigens, six cases with H type 2 accumulation and one case with incompatible expression were demonstrated in breast carcinoma. Thirty-one breast carcinomas which showed the deletion of A/B/H type 2 expressed the Lewis-related antigens more frequently than nine cases which showed compatible expression. These results suggested that the activation of terminal fucosyltransferase and sialyltransferase as well as inactivation of some glycosyltransferases had occurred in cancer cell membrane, and sialyl Lex, defined by a new monoclonal antibody CSLEX1, may be useful as a tumor-associated antigen independent of Lewis blood group type in breast cancer. PMID- 1905703 TI - Potential value of cetylmannoside-modified liposomes as carriers of macrophage activators to human blood monocytes. AB - The present study was undertaken to examine the potential value of cetylmannoside modified multilamellar liposomes (Man-MLV) as carriers for transfer of macrophage activators to blood monocytes. Highly purified blood monocytes were isolated by centrifugal elutriation from healthy donors under endotoxin-free conditions. Freshly prepared monocytes phagocytosed Man-MLV to a lesser extent than monocyte derived macrophages, but they took up Man-MLV much more effectively than control liposomes without cetylmannoside (control MLV). Phagocytosis of Man-MLV, but not control MLV by monocytes was inhibited by addition of D-mannose, but not of D galactose. Desmethyl-muramyl dipeptide (norMDP) entrapped in Man-MLV was far more effective than norMDP entrapped in MLV in activating monocytes to the tumoricidal state. The effect of encapsulation of recombinant human macrophage colony stimulating factor (M-CSF) in Man-MLV on prolongation of survival of monocytes was examined. Blood monocytes that had been incubated for up to 21 days with Man MLV containing 5-20 U of M-CSF per ml were effective in prolonging monocyte survival, but monocytes that had been incubated in medium with less than 50 U/ml of M-CSF or with control MLV containing 5-10 U of M-CSF showed no increase of monocyte survival over that in medium alone. Addition of rabbit anti-M-CSF antiserum did not affect survival prolongation of monocytes by M-CSF encapsulated in Man-MLV. We conclude that liposomes modified with cetylmannoside are far more effective than unmodified liposomes as a carrier to deliver biological response modifiers to human blood monocytes. PMID- 1905704 TI - Expression of a rat ovary-independent mammary tumor-associated antigen defined by a monoclonal antibody, TAK-B1. AB - A monoclonal antibody, TAK-B1, was produced by immunization of BALB/c mice with mammary carcinoma induced in inbred Sprague-Dawley rats by treatment with 7,12 dimethylbenz[a]anthracene. TAK-B1 reacted with ovary-independent mammary carcinoma cells which had been transformed from ovary-dependent mammary carcinoma cells, but did not react with original mammary carcinoma cells or with cells from mammary glands exhibiting fibrocystic changes or normal mammary glands. However, TAK-B1 reacted not only with basal cells of the epidermis and epithelial cells of the bottom portion of crypts of the small intestine in adult rats, but also with basal cells of epidermis in skin and mesenchymal cells around developing hair follicles in fetuses. We therefore classify TAK-B1 as an ovary-independent rat mammary tumor-associated antigen. Immunoelectron microscopic examinations revealed that the antigen recognized by TAK-B1 was localized in the cell surface membrane of ovary-independent mammary carcinoma cells. Immunoprecipitation assay revealed that the antigen recognized by TAK-B1 was composed of M 220,000 protein and four other minor proteins. PMID- 1905705 TI - Establishment of drug resistance in human gastric and colon carcinoma xenograft lines. AB - We established multidrug-resistant human gastric and colon xenograft lines by means of intratumoral injections of four agents, doxorubicin (DXR), cisplatin (CDDP), 5-fluorouracil (5-FU) and mitomycin C (MMC), into subcutaneous SC1NU and SW480 tumors once a week or less. Such intermittent drug exposure is commonly used in clinical chemotherapeutic protocols. All xenograft lines acquired resistance to the injected drugs as evaluated by in vivo drug-resistance tests. Many of the drug-resistant lines showed various patterns of cross resistance to other drugs. In order to analyze the mechanism of resistance in vivo, we investigated the expression of drug resistance gene, which has been extensively studied in vitro. We used four complementary DNAs (cDNAs) for multidrug resistance (MDR1), glutathione S-transferase-pi (GST-pi), thymidylate synthase (TS) and dehydrofolate reductase (DHFR), as probes. We observed GST-pi, DHFR and TS mRNA expression at various levels, but MDR1 mRNA expression was found only in SW480/DXR by the method of poly (A+) RNA selection. Four resistant SW480 lines had higher TS mRNA expressions. Six resistant lines had stronger GST-pi mRNA expression. Five resistant lines had higher DHFR mRNA expression. Drug resistance genes related to the treated drug were also expressed in this in vivo model; MDR1 in SW480/DXR, GST-pi in SW480/CDDP and in SC1NU/CDDP and TS in SW480/5-FU. In contrast to in vitro resistant lines which have been reported as models of drug resistance, the expression of drug resistance genes in vivo was not always correlated to the acquisition of cross resistance. These resistant xenograft lines and the methods developed to induce drug resistance in vivo should be useful for studies on the mechanism of drug resistance in the clinical setting. PMID- 1905706 TI - Photodynamic cell killing effects and acute skin photosensitivity of aluminum chloro-tetrasulfonated phthalocyanine and hematoporphyrin derivative. AB - Aluminum-chloro-tetrasulfonated phthalocyanine (PC) showing an absorption peak at 678 nm was compared to hematoporphyrin derivative (HpD), a photosensitizer commonly used in the photodynamic therapy (PDT) of cancers. IN VITRO STUDIES: KK 47 cells were exposed to long-wavelength ultraviolet (UVA) or red light (greater than 600 nm, greater than 640 nm and greater than 660 nm) after drug sensitization. With UVA irradiation, a higher photodynamic cell killing effect was observed in the cells treated with HpD than with PC. However, with red light irradiation (both greater than 640 nm and greater than 660 nm) PC resulted in greater cell damage. PC was less toxic to KK-47 cells in the dark. In vivo studies: Using a gold vapor laser (GVL: 627.8 nm, 200 mW/cm2, 200 J/cm2), the photodynamic tumor response was determined in C3H/He mice bearing transplantable squamous cell carcinoma. No significant difference was observed in the tumor volume between the PC and HpD groups, except that the PC group (10.0 mg/kg body weight) showed a significantly higher remission rate (3/6) than the control group (0/10, P less than 0.05). Skin photosensitivity test: Skin photosensitivity was estimated by measuring changes in back skin thickness due to photosensitization. With UVA irradiation, a stronger skin reaction was observed in the HpD group, while with visible light irradiation there was no significant difference between the HpD and PC groups. Based on the superior cell killing effect with red light, reduced toxicity to the cells in the dark and mild skin reaction with UVA, PC may be a more promising photosensitizer for PDT. PMID- 1905707 TI - A cooperative randomized study on tegafur plus mitomycin C versus combined tegafur and uracil plus mitomycin C in the treatment of advanced gastric cancer. AB - A randomized controlled trial involving 13 institutions in Japan was conducted in order to compare the efficacy of tegafur plus mitomycin C (MMC) (Regimen A) and UFT (a combination of uracil and tegafur at a molar ratio of 4 to 1) plus MMC (Regimen B) for patients with advanced gastric cancer, who had not received any prior cancer chemotherapy. Regimen A (tegafur + MMC) consisted of 5 mg of MMC/m2/week given intravenously, and 500 mg of tegafur/m2/day given orally. Regimen B consisted of the same schedule of MMC and 375 mg of UFT/m2/day given orally. One hundred and eighty-six patients with primary gastric cancer were entered; 183 were eligible and 3 were ineligible for the study. A total of 169 were evaluable for efficacy of the treatment, including 90 patients with Regimen A and 79 with Regimen B. A response rate of 7.8% (7/90 cases) for Regimen A and one of 25.3% (20/79 cases) for Regimen B were obtained, indicating a significantly higher response rate for Regimen B according to the Criteria for Evaluating Efficacy of Chemotherapy/Radiation Therapy in the Treatment of Gastric Cancer (P = 0.004). Regarding side effects, no marked differences in either severity or incidence were observed between the two groups. The group assigned to Regimen B showed a significant survival advantage after adjustment for major prognostic factors using a proportional hazards model (P = 0.0398). Moreover, a close correlation of antitumor effect and survival duration was found when the above criteria were used. PMID- 1905709 TI - Spatiotemporal development of cochlear innervation and hair cell differentiation in the rat. AB - The apical cytoskeleton of cochlear hair cells is largely comprised of actin microfilaments and actin-associated proteins, of which fodrin is one of the most prominent. We studied the development of this mechanosensory apical portion of cochlear hair cells of the rat by fluorescence microscopy using rhodamine conjugated phalloidin to detect F-actin and an antibody against alpha-fodrin. An antibody against the 160 kDa neurofilament polypeptide was used for tracing nerve fibers. The first sign of differentiation of the mechanosensory region, actin containing stereocilia, was observed on the 19th gestational day in the inner hair cells of the basal coil. The appearance of expression of cytoskeletal actin in the cochlear hair cells proceeded gradientally from basal to apical coil and from inner to outer hair cells. Corresponding maturation sequences were observed in the development of fodrin immunoreactivity in the cuticular plates, but the first evidence of this reactivity was found one day later than the appearance of stereocilia in the hair cells at the same location. Also the penetration of neurofilament-positive neurites into the sensory epithelium followed the same kind of longitudinal and radial maturation gradients throughout the cochlea. Fibers were revealed beneath the sensory cells shortly before the first appearance of differentiation of their mechanosensory region. The results suggest that ingrowing nerve fibers may influence the timing of the apical cytoskeleton differentiation in cochlear hair cells or that both these processes could be controlled by the same external signals that are gradientally expressed throughout the cochlea. PMID- 1905710 TI - Concentrations of insulin-like growth factor I and steroids in follicular fluid of preovulatory bovine ovarian follicles: effect of daily injections of a growth hormone-releasing factor analog and(or) thyrotropin-releasing hormone. AB - To determine whether long-term administration of growth hormone (GH)-releasing factor (GRF) and(or) thyrotropin-releasing hormone (TRH) alters ovarian follicular fluid (FFL) concentrations of insulin-like growth factor-I (IGF-I), progesterone, and estradiol (E2), and follicular growth, Friesian x Hereford heifers (n = 47; 346 +/- 3 kg) were divided into the following four groups: control (vehicle; n = 11); 1 micrograms GRF (human [Des NH2 Tyr1, D-Ala2, Ala15] GRF [1-29]-NH2).kg-1 BW.d-1 (n = 12); 1 microgram TRH.kg-1 BW.d-1 (n = 12); or GRF + TRH (n = 12). Daily injections (s.c.) continued for 86 d. On d 89, heifers that had been synchronized were slaughtered and ovaries were removed. Follicles were grouped by magnitude of diameter into the three following sizes: 1 to 3.9 mm (small, n = 55), 4.0 to 7.9 mm (medium, n = 63), and greater than or equal to 8 mm (large, n = 71). Growth hormone-releasing factor and(or) TRH did not affect (P greater than .10) IGF-I concentrations in FFL of any follicle size group. Growth hormone-releasing factor increased (P less than .06) size (means +/- pooled SE) of large follicles (14.7 vs 13.0 +/- .6 mm). Growth hormone-releasing factor also increased (P less than .05) progesterone concentrations 4.4-fold above controls in FFL of medium-sized follicles but had no effect on progesterone in FFL of the small or large follicles. Thyrotropin-releasing hormone did not alter FFL progesterone or E2 concentrations in any follicle size group. We conclude that the GRF and(or) TRH treatments we employed did not affect intra-ovarian IGF-I concentrations, but GRF may alter steroidogenesis of medium-sized follicles and growth of large follicles. PMID- 1905711 TI - Cystitis glandularis occurring in neurofibromatosis. AB - A case of cystitis glandularis occurring concurrently with a neurilemmoma of low malignant potential in a patient with neurofibromatosis is presented. The co existence of these two conditions made it difficult to distinguish between local recurrence of the neurilemmoma and malignant change in the cystitis glandularis. Repeated biopsies were required to solve this problem. The pathological and radiological features are described. PMID- 1905708 TI - Conagenin, a low molecular weight immunomodulator produced by Streptomyces roseosporus. PMID- 1905712 TI - Characterization of Bacillus subtilis recombinational pathways. AB - Recombination in Bacillus subtilis requires the products of numerous rec loci. To dissect the various mechanisms which may be involved in genetic recombination, we constructed a series of isogenic strains containing more than one mutant rec allele. On the basis of their impairment in genetic exchange, the various loci (represented by specific rec alleles) were classified into different epistatic groups. Group alpha consists of rec genes represented by recB, recD, recF, recG, recL, and recR mutations, while group beta comprises the addA and addB mutations. Group gamma consists of the recH and recP mutations. These results suggest that B. subtilis has multiple pathways for genetic recombination and that the products of the genes within the alpha, beta, and gamma epistatic groups are involved in these alternative recombination pathways. The RecA protein is required in all three pathways of intermolecular recombination. PMID- 1905713 TI - In vitro deletion mapping of the viral strand replication origin of Pseudomonas bacteriophage Pf3. AB - The origin of viral strand replication of the filamentous bacteriophage Pf3 has been characterized in Escherichia coli by in vitro deletion mapping techniques. The origin region was functionally identified by its ability to convey replicative properties to a recombinant plasmid in a polA host in which the replication origin of the vector plasmid is not functional. The origin of Pf3 viral strand replication is contained within a DNA sequence of 139 bp. This sequence covers almost completely one of the intergenic regions of the Pf3 genome, and it specifies both replication initiation and termination functions. Although no nucleotide sequence homology is present between the Pf3 origin of viral strand replication and that of the E. coli filamentous phages Ff (M13, f1, and fd) and IKe, their map positions and functional properties are very similar. PMID- 1905714 TI - A highly thermostable neutral protease from Bacillus caldolyticus: cloning and expression of the gene in Bacillus subtilis and characterization of the gene product. AB - By using a gene library of Bacillus caldolyticus constructed in phage lambda EMBL12 and selecting for proteolytically active phages on plates supplemented with 0.8% skim milk, chromosomal B. caldolyticus DNA fragments that specified proteolytic activity were obtained. Subcloning of one of these fragments in a protease-deficient Bacillus subtilis strain resulted in protease proficiency of the host. The nucleotide sequence of a 2-kb HinfI-MluI fragment contained an open reading frame (ORF) that specified a protein of 544 amino acids. This ORF was denoted as the B. caldolyticus npr gene, because the nucleotide and amino acid sequences of the ORF were highly similar to that of the Bacillus stearothermophilus npr gene. Additionally, the size, pH optimum, and sensitivity to the specific Npr inhibitor phosphoramidon of the secreted enzyme indicated that the B. caldolyticus enzyme was a neutral protease. The B. sterothermophilus and B. caldolyticus enzymes differed at only three amino acid positions. Nevertheless, the thermostability and optimum temperature of the B. caldolyticus enzyme were 7 to 8 degrees C higher than those of the B. stearothermophilus enzyme. In a three-dimensional model of the B. stearothermophilus Npr the three substitutions (Ala-4 to Thr, Thr-59 to Ala, and Thr-66 to Phe) were present at solvent-exposed positions. The role of these residues in thermostability was analyzed by using site-directed mutagenesis. It was shown that all three amino acid substitutions contributed to the observed difference in thermostability between the neutral proteases from B. stearothermophilus and B. caldolyticus. PMID- 1905715 TI - Arg-X-Lys/Arg-Arg motif as a signal for precursor cleavage catalyzed by furin within the constitutive secretory pathway. AB - Many peptide hormones are produced from larger precursors by endoproteolysis at pairs of basic amino acids (e.g. Lys-Arg and Arg-Arg) within the regulated secretory pathway in endocrine cells. However, many other secretory and membrane proteins appear to be produced from precursors through cleavage at multiple, rather than paired, basic residues within the constitutive secretory pathway in non-endocrine cells. By surveying various precursors processed constitutively, we noticed that most of them have the consensus sequence, Arg-X-Lys/Arg-Arg (RXK/RR), at the cleavage site. When expressed in endocrine and non-endocrine cells, a precursor with the RXKR sequence was cleaved in both types of cells, whereas that with the Lys-Arg pair was cleaved only in the endocrine cells. When the RXKR precursor was coexpressed with furin and PC3, both of which are mammalian homologues of the yeast precursor-processing endoprotease Kex2, in non endocrine cells, enhancement of the precursor cleavage by furin but not by PC3 was observed. By contrast, when the Lys-Arg precursor was coexpressed with the two mammalian proteases in endocrine cells with no endogenous processing activity at dibasic sites, it was cleaved only by PC3. These results indicate that the basic pair and the RXK/RR sequence are the signals for precursor cleavages catalyzed by PC3 within the regulated secretory pathway and by furin within the constitutive pathway, respectively. PMID- 1905716 TI - Rhodopsin and the retinal G-protein distinguish among G-protein beta gamma subunit forms. AB - The beta gamma subunits of G-proteins are composed of closely related beta 35 and beta 36 subunits tightly associated with diverse 6-10 kDa gamma subunits. We have developed a reconstitution assay using rhodopsin-catalyzed guanosine 5'-3-O (thio)triphosphate (GTP gamma S) binding to resolved alpha subunit of the retinal G-protein transducin (Gt alpha) to quantitate the activity of beta gamma proteins. Rhodopsin facilitates the exchange of GTP gamma S for GDP bound to Gt alpha beta gamma with a 60-fold higher apparent affinity than for Gt alpha alone. At limiting rhodopsin, G-protein-derived beta gamma subunits catalytically enhance the rate of GTP gamma S binding to resolved Gt alpha. The isolated beta gamma subunit of retinal G-protein (beta 1, gamma 1 genes) facilitates rhodopsin catalyzed GTP gamma S exchange on Gt alpha in a concentration-dependent manner (K0.5 = 254 +/- 21 nM). Purified human placental beta 35 gamma, composed of beta 2 gene product and gamma-placenta protein (Evans, T., Fawzi, A., Fraser, E.D., Brown, L.M., and Northup, J.K. (1987) J. Biol. Chem. 262, 176-181), substitutes for Gt beta gamma reconstitution of rhodopsin with Gt alpha. However, human placental beta 35 gamma facilitates rhodopsin-catalyzed GTP gamma S exchange on Gt alpha with a higher apparent affinity than Gt beta gamma (K0.5 = 76 +/- 54 nM). As an alternative assay for these interactions, we have examined pertussis toxin-catalyzed ADP-ribosylation of the Gt alpha subunit which is markedly enhanced in rate by beta gamma subunits. Quantitative analyses of rates of pertussis modification reveal no differences in apparent affinity between Gt beta gamma and human placental beta 35 gamma (K0.5 values of 49 +/- 29 and 70 +/- 24 nM, respectively). Thus, the Gt alpha subunit alone does not distinguish among the beta gamma subunit forms. These results clearly show a high degree of functional homology among the beta 35 and beta 36 subunits of G-proteins for interaction with Gt alpha and rhodopsin, and establish a simple functional assay for the beta gamma subunits of G-proteins. Our data also suggest a specificity of recognition of beta gamma subunit forms which is dependent both on Gt alpha and rhodopsin. These results may indicate that the recently uncovered diversity in the expression of beta gamma subunit forms may complement the diversity of G alpha subunits in providing for specific receptor recognition of G-proteins. PMID- 1905717 TI - Isolation and characterization of GTP cyclohydrolase I from mouse liver. Comparison of normal and the hph-1 mutant. AB - GTP cyclohydrolase I, an enzyme that catalyzes the first reaction in the pathway for the biosynthesis of pterin compounds, was purified from of C3H mouse liver by 192-fold to apparent homogeneity, using Ultrogel AcA34, DEAE-Trisacryl, and GTP agarose gels. Its native molecular weight was estimated at 362,000. When the enzyme was subjected to electrophoresis on a denaturing polyacrylamide gel, only one protein band was evident, and its molecular weight was estimated at 55,700. The NH2-terminal amino acid of this enzyme was serine. These results indicate the enzyme consists of six to eight subunits. No coenzyme or metal ion was required for activity. This enzyme activity was inhibited by most of divalent cations and was slightly activated by potassium ion. The Km value for GTP was determined to be 17.3 microM. The temperature and pH optima for the activity were 60 degrees C and pH 8.0-8.5, respectively. The expected products, a dihydroneopterin compound and formic acid, were found in a molar ratio of 1.01. A polyclonal antiserum generated against the purified enzyme was used to compare GTP cyclohydrolase I from the hph-1 mutant and normal mouse. The hph-1 mutant liver contained only 8% of normal specific activity, but a normal amount of GTP cyclohydrolase I antigen as compared with the C3H mouse. Subunit molecular weight and electrophoretic behavior of GTP cyclohydrolase I from hph-1 mutant were not different from those of the enzyme from C3H mouse. These results suggest that the hph-1 mutation may involve alteration of the catalytic site but does not detectably alter the whole enzyme structure. PMID- 1905719 TI - Expression of a full-length cDNA coding for human intestinal lactase-phlorizin hydrolase reveals an uncleaved, enzymatically active, and transport-competent protein. AB - Lactase-phlorizin hydrolase (LPH) (EC 3.2.1.23/62) is a major intestinal microvillar membrane glycoprotein that digests lactose, the main carbohydrate of milk. To investigate structure/function relationships of LPH and to assess the impact of intracellular processing on the function of LPH and on its transport to the cell surface, we have expressed a full-length cDNA encoding LPH in mammalian COS-1 cells. Analysis of the expressed protein by immunoprecipitation with monoclonal anti-LPH antibodies and treatments with endo-beta-N acetylglucosaminidase H and sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed two polypeptides with apparent molecular masses of 215 and 230 kDa, representing the mannose-rich (pro-LPHh) and complex (pro-LPHc) glycosylated forms of the precursor. By contrast to pro-LPH in human enterocytes, the expressed pro-LPH in COS-1 cells does not undergo intracellular proteolytic cleavage to generate a form similar to the mature enzyme of the brush-border membrane. Intracellular cleavage, however, is not essential for the molecule to acquire its enzymatic activity since pro-LPH in COS-1 cells is enzymatically as active as LPH isolated from intestinal brush-border membranes. Indirect immunofluorescent staining of transfected cells demonstrated that pro-LPH is expressed at the cell surface. This was further corroborated by the sensitivity of the complex glycosylated form (pro-LPHc) to trypsin in the medium. Our results provide the first conclusive evidence that pro-LPH is an enzymatically active molecule and that the intracellular proteolysis of pro-LPH is not essential for the generation of transport-competent forms of LPH. PMID- 1905718 TI - Sequence and characterization of Bacillus subtilis CheB, a homolog of Escherichia coli CheY, and its role in a different mechanism of chemotaxis. AB - The Bacillus subtilis gene encoding CheB, which is homologous to Escherichia coli CheY, the regulator of flagellar rotation, has been cloned and sequenced. It has been verified, using a phage T7 expression system, by showing that a small protein, the same size as E. coli CheY, is actually made from this DNA. Despite the fact that the two proteins are 36% identical, with many highly conserved residues, they appear to play different roles. Unlike CheY null mutants, which swim smoothly, CheB null mutants tumble incessantly. However, a CheB point mutant swims smoothly, even in the presence of a plasmid bearing cheB, which restores the null mutants to wild type. Expression of CheB in wild type B. subtilis makes the cells exhibit more tumbling. Since both absence of CheB and presence of high levels of CheB cause tumbling, CheB appears to be required, in certain circumstances, for both smooth swimming and tumbling. Expression in wild type E. coli makes the cells smooth swimmers and strongly inhibits chemotaxis. PMID- 1905720 TI - Independent assembly and secretion of a dimeric adhesive domain of von Willebrand factor containing the glycoprotein Ib-binding site. AB - von Willebrand factor (vWF) is a multimeric glycoprotein that supports platelet adhesion on thrombogenic surfaces as part of the normal hemostatic response to vascular injury. We have employed a domain-specific expression strategy to analyze the biosynthetic processing steps and minimum structural requirements for assembly of the platelet receptor glycoprotein Ib-binding domain of vWF. A chimeric cDNA that codes for the vWF signal peptide and a segment of vWF internal primary sequence, residues 441-730, directs the secretion of a functional vWF fragment from mammalian cells. The recombinant molecule intrinsically assembles through intermolecular disulfide bond formation into a dimeric adhesive domain without contributions from other regions of vWF, including propeptide, previously indicated as essential for vWF multimer assembly. Prevention of N-linked glycosylation on the recombinant domain does not impair dimer formation or the ability to support platelet aggregation. These results identify a minimum structural element for vWF subunit assembly and provide new insights into the processing steps to produce vWF multimers and adhesive domains. PMID- 1905721 TI - Studies on the reduction of endogenously generated prostaglandin G2 by prostaglandin H synthase. AB - Prostaglandin H synthase oxidizes arachidonic acid to prostaglandin G2 (PGG2) via its cyclooxygenase activity and reduces PGG2 to prostaglandin H2 by its peroxidase activity. The purpose of this study was to determine if endogenously generated PGG2 is the preferred substrate for the peroxidase compared with exogenous PGG2. Arachidonic acid and varying concentrations of exogenous PGG2 were incubated with ram seminal vesicle microsomes or purified prostaglandin H synthase in the presence of the reducing cosubstrate, aminopyrine. The formation of the aminopyrine cation free radical (AP.+) served as an index of peroxide reduction. The simultaneous addition of PGG2 with arachidonic acid did not alter cyclooxygenase activity of ram seminal vesicle microsomes or the formation of the AP.+. This suggests that the formation of AP.+, catalyzed by the peroxidase, was supported by endogenous endoperoxide formed from arachidonic acid oxidation rather than by the reduction of exogenous PGG2. In addition to the AP.+ assay, the reduction of exogenous versus endogenous PGG2 was studied by using [5,6,8,9,11,12,14,15-2H]arachidonic acid and unlabeled PGG2 as substrates, with gas chromatography-mass spectrometry techniques to measure the amount of reduction of endogenous versus exogenous PGG2. Two distinct results were observed. With ram seminal vesicle microsomes, little reduction of exogenous PGG2 was observed even under conditions in which all of the endogenous PGG2 was reduced. In contrast, studies with purified prostaglandin H synthase showed complete reduction of both exogenous and endogenous PGG2 using similar experimental conditions. Our findings indicate that PGG2 formed by the oxidation of arachidonic acid by prostaglandin H synthase in microsomal membranes is reduced preferentially by prostaglandin H synthase. PMID- 1905722 TI - Structural basis for the decreased procoagulant activity of human factor VIII compared to the porcine homolog. AB - The stability of activated human and porcine factor VIII (fVIII) differ, but a direct comparison of their structural and functional properties has not been made. Highly purified, heterodimeric human recombinant and porcine plasma-derived fVIII were exchanged into a common buffer and some minor contaminants were removed by anion-exchange chromatography. The activations of human and porcine fVIII by thrombin were studied by a two-stage coagulation assay using human citrated plasma as the standard. The peak activation of porcine fVIII was 10-fold greater than human fVIII (1.1 x 10(6) unit/mg versus 1.1 x 10(5) unit/mg). The proteolytic fragmentation of fVIII by thrombin was evaluated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and was not different between human and porcine fVIII, yielding previously identified bands corresponding to fragments A1, A2, A3-C1-C2, and the B domain. Following activation by thrombin, human fVIII was subjected to cation-exchange (Mono S) high performance liquid chromatography at pH 6.0 under conditions that yields stable, heterotrimeric (A1/A2/A3-C1-C2) porcine fVIIIaIIa (Lollar, P., and Parker, C.G. (1990) Biochemistry 28, 666-674). Coagulant activity was recovered in a single peak that was less than 0.5% that of porcine fVIIIaIIa (1.2 x 10(4) unit/mg versus 2.6 x 10(6) unit/mg). Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the peak fraction revealed bands corresponding to the A3-C1-C2 and A1 fragments but only trace levels of the A2 fragment. In contrast, activation of human fVIII by thrombin followed by Mono S HPLC at pH 5.0 produced a peak with 10-fold greater activity (1.2 x 10(5) unit/mg) than at pH 6.0 and which contained significant amounts of the A2 fragment. We conclude that human fVIIIIIa, like porcine fVIIIIIa, is a heterotrimer and propose that its apparent decreased coagulant activity is due to weaker association of the A2 subunit. PMID- 1905723 TI - Low basal transcription of genes for tissue-specific collagens by fibroblasts and lymphoblastoid cells. Application to the characterization of a glycine 997 to serine substitution in alpha 1(II) collagen chains of a patient with spondyloepiphyseal dysplasia. AB - Cultured dermal fibroblasts were shown, using amplification of cDNA by the polymerase chain reaction, to produce very low levels of spliced transcripts from the COL2A1 gene that encodes the cartilage-specific alpha 1(II) chains of type II collagen. Cultured lymphoblastoid cells were also shown to produce very low levels of spliced transcripts from the COL1A1 and COL1A2 genes that encode the alpha 1(I) and alpha 2(I) chains of type I collagen, the COL2A1 gene that encodes type II collagen, and the COL3A1 gene that encodes the alpha 1(III) chains of type III collagen. Amplified cDNAs prepared from lymphoblastoid cells were used to identify previously characterized heterozygous mutations in the COL1A1 and COL1A2 genes from two patients with osteogenesis imperfecta and in the COL3A1 gene from a patient with the Ehlers-Danlos syndrome type IV. Amplified alpha 1(II) cDNA from fibroblasts and lymphoblastoid cells of a child with spondyloepiphyseal dysplasia congenita was also used to localize sequence mismatches using chemical modification of cDNA:cDNA heteroduplexes by hydroxylamine and cleavage with piperidine. The amplification products containing the mismatched region were sequenced and the mutation was shown to change the codon GGC for glycine 997 to AGC for serine in the triple helical domain of the alpha 1(II) chains. The corresponding region of the genomic DNA was sequenced and the heterozygous point mutation was shown to be in exon 48 of the COL2A1 gene. Allelic restriction mapping showed that neither parent carried the mutation in their leucocytes. This mutation emphasizes the importance of COL2A1 mutations in producing the spondyloepiphyseal dysplasia phenotype. The low basal rate of transcription ("illegitimate transcription"), splicing, and polyadenylation of tissue-specific mRNAs by cultured dermal fibroblasts and lymphoblastoid cells provides the opportunity to localize and sequence mutations in amplified cDNA in patients from whom affected tissue is unavailable. PMID- 1905724 TI - Gabaculine-resistant glutamate 1-semialdehyde aminotransferase of Synechococcus. Deletion of a tripeptide close to the NH2 terminus and internal amino acid substitution. AB - Glutamate 1-semialdehyde aminotransferase (GSA-AT) is the last enzyme in the C5 pathway converting glutamate into the tetrapyrrole precursor delta aminolevulinate in plants, algae, and several bacteria. Sequence analysis of the genes encoding GSA-AT in barley, Synechococcus, and Escherichia coli revealed 50 70% similarity in the primary structures of the proteins. The enzyme is inhibited rapidly by gabaculine when added in approximately stoichiometric amounts with the enzyme. A gabaculine-tolerant Synechococcus strain, GR6, was found to produce a GSA-AT less sensitive to the inhibitor. Accordingly, the mutant gene was isolated and sequenced. In comparison with the wild-type gene it contains a deletion of nine nucleotides (position 12-20) and a guanine to adenine substitution (position 743). This resulted in the loss of the amino acids serine, proline, and phenylalanine (position 5-7) close to the NH2 terminus of the enzyme and an exchange of Met-248 for isoleucine in the middle of the polypeptide chain. Wild type and mutant GSA-AT were expressed in E. coli and purified close to homogeneity. Although the specific activity of the mutant GSA-AT was only one fifth of the wild type, it displayed a 100-fold increased resistance to gabaculine. Peaks in the absorption spectrum of the purified recombinant GSA-ATs at 335 and 417 nm are typical of a transaminase containing a B6 cofactor. Incubation with substrate and with inhibitor induced spectral changes characteristic of other gabaculine-sensitive, B6-requiring enzymes. PMID- 1905725 TI - Eicosanoid forming enzyme mRNA in human tissues. Analysis by quantitative polymerase chain reaction. AB - The key enzymes in the formation of eicosanoids, including leukocyte 5 lipoxygenase (5LX), platelet 12-lipoxygenase (12LX), reticulocyte 15-lipoxygenase (15LX), prostaglandin G/H synthase cyclooxygenase, and leukotriene A4 (LTA) hydrolase have been studied extensively in recent years. Little is known, however, about the regulation of these enzymes at the gene level. We have developed a quantitative polymerase chain reaction (PCR) assay to quantify the mRNAs for these five enzymes, as well as for cytoplasmic beta-actin (bACT) mRNA. Human erythroleukemia (HEL) cells, which display megakaryocytic/erythroid characteristics, were selected as a source of RNA to characterize the assay. These cells expressed mRNA for bACT, LTA, cyclooxygenase, and 12LX (in decreasing order). mRNA for 5LX and 15LX was undetectable. Bronchoalveolar lavage fluid cells obtained from asthmatic patients, primarily alveolar macrophages, contained mRNA for bACT, LTA, 5LX, cyclooxygenase, and 15LX (in decreasing order). Treatment of HEL cells with phorbol 12-myristate 13-acetate or steroid administration to asthmatic patients apparently selectively regulated certain of these target genes. The utility of this assay in quantifying mRNA for the various target genes in blood cells, including platelets from patients with chronic myelogenous leukemia, has also been demonstrated. Studies on the regulation of genes for enzymes involved in the leukotriene and prostaglandin biosynthetic pathways, especially when only small tissue samples are available, will be facilitated with this approach. PMID- 1905726 TI - Crystal structure of activated ribulose-1,5-bisphosphate carboxylase complexed with its substrate, ribulose-1,5-bisphosphate. AB - The three-dimensional structure of the complex of ribulose-1,5-bisphosphate carboxylase from Rhodospirillum rubrum, CO2, Mg2+, and ribulose bisphosphate has been determined with x-ray crystallographic methods to 2.6-A resolution. Ribulose 1,5-bisphosphate binds across the active site with the two phosphate groups in the two phosphate binding sites of the beta/alpha barrel. The oxygen atoms of the carbamate and the side chain of Asp-193 provide the protein ligands to the bound Mg2+ ion. The C2 and the C3 or C4 oxygen atoms of the substrate are also within the first coordination sphere of the metal ion. At the present resolution of the electron density maps, two slightly different conformations of the substrate, with the C3 hydroxyl group "cis" or "trans" to the C2 oxygen, can be built into the observed electron density. The two different conformations suggest two different mechanisms of proton abstraction in the first step of catalysis, the enolization of the ribulose 1,5-bisphosphate. Two loop regions, which are disordered in the crystals of the nonactivated enzyme, could be built into their respective electron density. A comparison with the structure of the quaternary complex of the spinach enzyme shows that despite the different conformations of loop 6, the positions of the Mg2+ ion, and most atoms of the substrate are very similar when superimposed on each other. There are, however, some significant differences at the active site, especially in the metal coordination sphere. PMID- 1905727 TI - Regional and mechanistic differences in platelet-derived growth factor-isoform induced alterations in cytosolic free calcium in porcine vascular smooth muscle cells. AB - Three specific platelet-derived growth factor (PDGF) isoforms are thought to bind with differing affinities to two distinct PDGF receptors which undergo activation following dimerization. Recent evidence has been presented that marked differences exist between the ability of PDGF-AA versus PDGF-AB and PDGF-BB to stimulate alterations in second messengers in cultures of vascular smooth muscle cells (VSMC), a result which was thought to be due to low numbers of the A-type receptor in this cell type (Sachinidis, A., Locker, R., Vetter, W., Tatje, D., and Hoppe, J. (1990) J. Biol. Chem. 265, 10238-10243, 1990). In particular, PDGF BB and PDGF-AB but not PDGF-AA could elicit alterations in cytosolic free calcium (Ca2+i). However, because these studies were performed on large cell populations using biochemical assays of PDGF activity, a minor PDGF-AA-Ca(2+)-responsive population of cells might go undetected. To test this possibility, VSMC were isolated from either thoracic or abdominal pig aorta, and alterations in Ca2+i were monitored using Multiparameter Digitized Video Microscopy following stimulation with PDGF isoforms alone, or either before or after exposure of VSMC to 5 mM EGTA. PDGF-AA-responsive cells were found to exist only in cultures of thoracic VSMC, caused oscillations in Ca2+i, represented 20% of the PDGF-BB responsive cells, and were subsequently responsive to PDGF-BB. PDGF-BB elicited monophasic alterations in Ca2+i in both thoracic and abdominal VSMC. Prior addition of EGTA inhibited PDGF-AA but not PDGF-BB-induced alterations in Ca2+i. Addition of EGTA during PDGF-AA-induced Ca2+i oscillations inhibited subsequent oscillations in Ca2+i, while addition of EGTA at the peak of the PDGF-BB Ca2+ response resulted in a more rapid return of Ca2+i to prestimulation levels. These data suggest that regional differences in the distribution of PDGF-A- and B-type receptor exists in vivo, and that activation of the A- and B-type PDGF receptors results in distinct alterations in Ca2+i. PMID- 1905728 TI - Siiyama (serine 53 (TCC) to phenylalanine 53 (TTC)). A new alpha 1-antitrypsin deficient variant with mutation on a predicted conserved residue of the serpin backbone. AB - alpha 1-antitrypsin (alpha 1AT), a plasma serine protease inhibitor, increases the risk of precocious pulmonary emphysema in individuals when deficient. Although more than 25 years have passed since a deficiency in the serum level of alpha 1AT was reported, it is only recently that the consequence of the amino acid replacement which leads to the deficient state has been discussed in terms of the crystallographic structure of alpha 1AT and the amino acid residues conserved in the superfamily to which it belongs. Our case involved a 38-year-old Japanese male with alpha 1AT deficiency which was analyzed and identified as a new deficient variant. The serum alpha 1AT of the proband migrated to the S position of the reference serum which is more cathodal than M1, the predominant normal variant, when isoelectric focusing (pH 4.2-4.9) is performed by a combination of Western blotting and crossed immunoelectrophoresis. The new deficient variant is designated as Siiyama after his birthplace. Although liver biopsy specimen showed no apparent pathological findings, PAS-positive with diastase-resistant inclusion bodies and immunoreactive aggregates were detected in several hepatocytes. In addition, similar alpha 1AT mRNA transcript levels were observed in peripheral blood leukocytes from the proband and healthy subjects by Northern analysis. All the coding exons (exon Ic, II, III, IV, and V) of the alpha 1AT gene of the proband and his family were amplified by polymerase chain reaction and followed by direct sequencing. A single missense mutation, Ser53 (TCC) to Phe53 (TTC was identified in exon II of the proband's alpha 1AT gene. All his family examined were heterozygous at this base. Ser53 is one of the most conserved residues as predicted by Huber and Carrell (Huber, R., and Carrell, R. W. (1989) Biochemistry 28, 8951-8966) and is thought to contribute to the organization of the internal core element of the alpha 1AT molecule. The mutational matrix number of Ser to Phe substitution is -3, indicating that this change is evolutionally rare. In this regard, a possible explanation for the deficient state in alpha 1AT Siiyama is that the change from an uncharged polar to a nonpolar amino acid imposed on the conserved serpin backbone exerts severe effects on the integrity of the molecule, and hence alters the intracellular processing of alpha 1AT. PMID- 1905729 TI - The posttranslationally modified C-terminal structure of bovine aortic smooth muscle rhoA p21. AB - rhoA p21, a ras p21-like small GTP-binding protein, has the same C-terminal consensus motif of Cys-A-A-X (A is an aliphatic amino acid and X is any amino acid) as ras p21s, which is posttranslationally processed. We here determine the posttranslationally processed C-terminal structure of the rhoA p21 purified from bovine aortic smooth muscle. Incubation of rhoA p21-expressing insect cells with exogenous [3H]mevalonolactone caused the labeling of rhoA p21, suggesting that rhoA p21 is prenylated. Consistently, Raney nickel treatment of rhoA p21 released a geranylgeranyl moiety as estimated by gas chromatography/mass spectrometry. No lipid moiety was released by KOH or NH2OH treatment. Extensive digestion of rhoA p21 with Achromobacter protease I yielded a C-terminal peptide, Ser-Gly-Cys190, that lacked the three C-terminal amino acids predicted from the cDNA but was geranylgeranylated and carboxyl methylated at the cysteine residue. Bovine brain cytosol geranylgeranylated the bacterial rhoA p21 having the three C-terminal amino acids predicted from the cDNA but not the protein lacking the three C terminal amino acids. Bovine brain membranes methylated the synthetic C-terminal peptide with 10 amino acids of rhoA p21 which was geranylgeranylated at its C terminal cysteine residue but not the peptide which was not geranylgeranylated. These results suggest that rhoA p21 is first geranylgeranylated followed by removal of the three C-terminal amino acids and the subsequent carboxyl methylation of the exposed cysteine residue. PMID- 1905731 TI - Identification of two novel GTP-binding protein alpha-subunits that lack apparent ADP-ribosylation sites for pertussis toxin. AB - Molecular cloning of cDNAs encoding alpha-subunits of guanine nucleotide-binding regulatory proteins (G-proteins) has revealed the existence of nine species of alpha-subunits. We have identified two additional G-protein alpha-subunits, which we refer to as GL1 alpha and GL2 alpha, by isolating bovine liver cDNA clones that cross-hybridized at reduced stringency with bovine Gi1 alpha-subunit cDNA. The deduced amino acid sequences of GL1 alpha and GL2 alpha share 83% identity with each other and show 45-55% identity with those of other known G-protein alpha-subunits. Both GL1 alpha and GL2 alpha lack a consensus site for ADP ribosylation by pertussis toxin. Messenger RNA corresponding to GL2 alpha was detected in all tissues examined, but GL1 alpha mRNA was detected only in liver, lung, and kidney. Antiserum prepared against a synthetic pentadecapeptide corresponding to the deduced carboxyl terminus of GL2 alpha specifically reacted with a 40-kDa protein in mouse liver, brain, lung, heart, kidney, and spleen. The amount of the 40-kDa protein was highest in brain and lung. We suggest that GL1 alpha and GL2 alpha are new members of a subfamily of pertussis toxin-insensitive G-proteins. PMID- 1905730 TI - Mapping of the mastoparan-binding site on G proteins. Cross-linking of [125I Tyr3,Cys11]mastoparan to Go. AB - Mastoparan (MP) activates GTP-binding regulatory proteins (G proteins) by promoting GDP/GTP exchange through a mechanism similar to that of G protein coupled receptors (Higashijima, T., Burnier, J., and Ross, E. M. (1990) J. Biol. Chem. 265, 14176-14186). [Tyr3, Cys11]MP was synthesized and shown to have regulatory activity similar to that of mastoparan when assayed in the presence of dithiothreitol (DTT). Activation by [Tyr3,Cys11]MP in the absence of DTT was complex in its kinetics, concentration dependence, and dependence on detergents. [125I-Tyr3,Cys11]MP bound covalently to the alpha subunit of G proteins. Cross linking was blocked by mastoparan or [Tyr3,Cys11]MP. Cross-linking was enhanced by the addition of beta gamma subunits, but no cross-linking to beta gamma subunits was observed. Cross-linking was inhibited by incubation of Go with guanosine 5'-O-(thiotriphosphate) and Mg2+ and was reversed by incubation with DTT or 2-mercaptoethanol. Stoichiometry of labeling was consistent with the cross linking of one molecule of [125I-Tyr3,Cys11]MP/alpha subunit, and CNBr hydrolysis of the [125I-Tyr3,Cys11]MP-alpha o adduct yielded one major labeled peptide fragment of approximately 6 kDa. Amino acid sequencing of this CNBr fragment prepared from recombinant alpha o showed that cross-linking occurred at Cys3. No alpha o sequence was obtained from the same fragment prepared from bovine brain alpha o, which is blocked by a myristoyl group at Gly2. Regulation of Go by MP was eliminated by tryptic proteolysis of the amino-terminal region. These observations suggest that the amino-terminal region of G protein alpha subunits contributes to the mastoparan-binding site, which may also be the receptor binding site, and is involved in regulation of nucleotide exchange. PMID- 1905733 TI - Primary nursing and the role of the nurse preceptor in changing long-term mental health care: an evaluation. AB - The main aims of this action research study were to implement primary nursing in two long-term psychiatric rehabilitation/continuing-care wards and to investigate the effects of the intervention of the quality of nursing care provision. This evaluation took the form of a quasi-experimental time series analysis. A package of measures together with a number of peripheral indicators was used before primary nursing was introduced on each ward and again after primary nursing had become established. The results showed that the implementation of primary nursing led to nurses being more accountable for care, resident who were seen to be more self-sufficient and independent and wards which had an improved environment for care and rehabilitation. PMID- 1905732 TI - High-performance liquid chromatographic procedures for the quantitative analysis of 15 tetracycline derivatives in small blood samples. AB - Published high-performance liquid chromatographic (HPLC) methods for the determination of tetracyclines are modified to determine low levels of each of 15 tetracycline derivatives in small blood samples. The rapid and accurate methods are applicable to pharmacokinetic studies in small experimental animals. The chromatographic procedures allow run times ranging from 2.1-7.3 min using different reversed-phase materials as supports and eluents based on acetonitrile or isopropanol-diethanolamine-EDTA. Detection limits are estimated at 10-500 ng/mL according to the derivative analyzed. The extraction from plasma is based on acidic precipitation of the plasma proteins using trifluoroacetic acid (TFA). The recovery of 13 derivatives from spiked plasma samples (100 micrograms/mL) reached 85-94% (n = 5). The precision data, expressed as coefficient of variation, ranged between 2.1 to 9.1% within run (n = 10) and 4.3 to 11.0% between day (n = 8) respectively. PMID- 1905734 TI - Research. From clinical trial to health policy--research on urinary incontinence in the adult, Part I. PMID- 1905735 TI - An opinion piece: the consensus conference. PMID- 1905736 TI - Long-term enteral feeding: the British view. PMID- 1905737 TI - Acute effects of Parlodel-LAR and response to long-term treatment with bromocriptine in a patient with a follicle stimulating hormone-secreting pituitary adenoma. AB - A 68-year-old male patient presented with visual impairment due to a large pituitary tumor. After transsphenoidal adenomectomy the elevated serum FSH levels were lowered but not normalized. Deterioration of the vision was detected five years later and tumor regrowth was evidenced. The patient was treated with the long-acting and repeatable form of bromocriptine (Parlodel-LAR). Three days after the first intramuscular injection it already resulted in an important improvement of the visual field defects. Serum FSH concentration was suppressed during a prolonged period, but no change in the size of the pituitary adenoma was recorded on CT scan. Long-term oral treatment with bromocriptine resulted in a sustained suppression of the serum FSH levels, without further visual improvement, but with a significant reduction of the volume of the adenoma. The rapid and prolonged effect of Parlodel-LAR upon the FSH secretion, with a possible correction of the visual field defects and a reduction of the tumor mass, could make this medication appropriate as adjunctive treatment in some gonadotroph cell adenomas. PMID- 1905739 TI - Antibiotic resistance in long-term care facilities. PMID- 1905738 TI - Effect of gestational mastectomy on postpartum gonadotropin releasing hormone and thyrotropin releasing hormone-induced luteinizing hormone and prolactin response in first lactation Holstein cattle. AB - First lactation Holstein cows were divided into two treatment groups to evaluate thyrotropin releasing hormone (TRH, 0.25 microgram/kg body weight) and gonadotropin releasing hormone (GnRH; 200 micrograms) induced secretion of prolactin (PRL) and luteinizing hormone (LH) on days 7 and 16 postpartum. Disregarding treatment, LH response was greater (p less than 0.01) on day 16 than day 7 postpartum (7.5 +/- 0.3 ng/ml on day 7 vs 10.2 +/- 0.3 ng/ml serum on day 16). Mastectomized cattle had similar time for initiation of LH increase, but peak concentrations were achieved later. Peak PRL concentrations were reached 12 to 15 min after injection and returned to baseline within 2.5 h in both groups. However, intact cows had higher (p less than 0.01) mean serum PRL than the mastectomized cows for 1 h following injection. Peak PRL concentration was 83.3 +/- 17.6 ng/ml for mastectomized cows vs 128.0 +/- 24.7 ng/ml for intact cows. It appears that udder removal allows for greater pituitary responsiveness to GnRH but diminishes PRL response to TRH suggesting the mammary gland differentially affects pituitary secretion of LH and PRL. PMID- 1905741 TI - [Case posing a therapeutic problem due to gastrointestinal hemorrhage caused by a factor VIII inhibitor following antibiotic administration]. PMID- 1905740 TI - Characterization of antibodies to advanced glycosylation end products on protein. AB - Antibodies directed against advanced glycosylation end products (AGEs) formed during a Maillard reaction have been generated and characterized. Since protein bound AGEs recognized by the antibodies were labile to acid hydrolysis, the antibodies were further characterized by using the AGE-alpha-acetyl-L-lysine methyl ester (AGE-ALME) with a brown and fluorescent property as well as the AGE proteins. The antibodies reacted with fluorescent compounds, rather than brown pigment compounds, in the AGE-ALME. The fluorescent compounds in the AGE-ALME were separated into four fluorescent compounds by reversed-phase thin layer chromatography (TLC). Of the fluorescent compounds tested, compound 3 (Rf = 0.63), as designated on a TLC plate, showed the highest affinity for the antibodies. In addition, the antibody recognition to the cross-linked oligomers with fluorescence in the AGE-protein was investigated by using bovine pancreatic ribonuclease A (RNase), which is known as a model protein for studying AGE induced cross-linking. Fluorescence in the AGE-RNase existed in both of the oligomers and the monomer. The cross-linked oligomers exhibited higher affinity to the antibodies than did the monomer, which has a similar degree of fluorescent intensity. These results indicate that our antibodies against cross-linked protein-bound AGEs may serve as a useful tool to elucidate pathophysiological roles of advanced Maillard reaction in diabetic complications and aging processes. PMID- 1905742 TI - Heterotopic ossification in a finger following head injury. AB - A case of digital periarticular heterotopic ossification is described. Such cases are extremely rare and diagnosis may be delayed. Spasticity, possibly in association with minor trauma, may contribute to the development of the process. Little experience exists of the management of such problems and a mobile joint may be difficult to achieve. PMID- 1905743 TI - A morphologic study of unfertilized oocytes and abnormal embryos in human in vitro fertilization. AB - The morphology of human, unfertilized oocytes and abnormal embryos cultured in vitro for 48-72 hr was examined in an attempt to learn more about oocyte maturation and reproductive failure in in vitro fertilization (IVF). About 21% of the unfertilized oocytes were totally degenerated. The majority (56%) of the remaining oocytes was arrested at the metaphase II stage. They contained coherent chromosomal plates and had extruded the first polar body with nuclear material. About 13% of oocytes underwent spontaneous activation. In most of these cases the second polar body was retained and many subnuclei or one big nucleus was formed. Five percent of metaphase II oocytes penetrated by sperm were not activated, likely as a result of oocyte immaturity. The developmental ability of abnormal embryos was poor. Several one-cell-stage zygotes were arrested at the pronuclear stage or at mitosis of the first mitotic division. Polyspermic embryos, especially those which contained four or more pronuclei, did not divide or formed uneven, multinucleated blastomeres. However, some triploid and tetraploid embryos often appeared normal morphologically despite their lethal chromosomal abnormalities. PMID- 1905744 TI - Subconjunctival high dose plasminogen activator in rabbit filtration surgery. AB - The primary cause of failure in glaucoma filtration surgery is fibroblastic proliferation and subconjunctival fibrosis at the bleb site resulting in decreased aqueous flow. We evaluated New Zealand white rabbits in a masked, placebo controlled pilot study to determine the potential reduction of episcleral fibrosis at the surgical bleb site utilizing 0.3 mls of: balanced salt solution (n = 11); an inert gel delivery vehicle (n = 13); the gel delivery vehicle with incorporated recombinant tissue plasminogen activator (tpa; n = 14), 1 mg/ml. Statistical analysis of computer assisted area measurements from multiple histologic sections demonstrated a significant decrease in episcleral fibrosis in the t-PA group as compared to the two other groups (p less than 0.05). Results from the t-PA group did not demonstrate an effect on intraocular pressure. There was no clinical evidence of toxicity or healing complications in the t-PA group. PMID- 1905745 TI - Chronic illness and the physician-patient relationship: a response to the Hastings Center's "ethical challenges of chronic illness". AB - The following article is a response to the position paper of the Hastings Center, "Ethical Challenges of Chronic Illness", a product of their three year project on Ethics and Chronic Care. The authors of this paper, three prominent bioethicists, Daniel Callahan, Arthur Caplan, and Bruce Jennings, argue that there should be a different ethic for acute and chronic care. In pressing this distinction they provide philosophical grounds for limiting medical care for the elderly and chronically ill. We give a critical survey of their position and reject it as well as any attempt to characterize the physician-patient relationship as a commercial contract. We emphasize, as central features of good medical practice, a commitment to be the patient's agent and a determination to acquire and be guided by knowledge. These commitments may sometimes conflict with efforts to have the physician serve as an instrument of social and economic policies limiting medical care. PMID- 1905746 TI - Metabolic and behavioural consequences of the procedures of the doubly labelled water technique on white (MF1) mice. AB - The effects of the doubly labelled water technique (intraperitoneal injection, temporary food deprivation and blood sampling) on the energy expenditure, food intake and behaviour of 18 white (MF1) mice was investigated. There were no significant differences in mean energy expenditure or food intake between experimental and control animals, on which the techniques were not performed, over the first 24 h after manipulation. These data indicate that there are no direct metabolic consequences associated with the procedures. During the 100 min immediately after blood sampling, the behaviour of experimental animals involved significantly more grooming, mostly at the site of the blood sample wound, more feeding and more general activity, at the expense of resting, when compared with controls. Twenty hours later the behavioural differences were less marked, but still statistically significantly different, and reversed: experimental animals spent more time resting and less in general activity or feeding. The effects of the technique on the behaviour of white mice had trivial consequences for their daily energy expenditure. This may reflect the restricted behavioural repertoire of these captive animals within respirometry chambers. The effect on wild animals may be more profound and requires investigation. PMID- 1905747 TI - The shaker and shaking-B genes specify elements in the processing of gustatory information in Drosophila melanogaster. AB - Mutations that affect the physiological properties of neurones or the development of neuronal circuits are likely to have profound effects on sensory and motor pathways. We have examined the effects of mutations in two loci--the Shaker complex and shaking-B-on the taste pathway of Drosophila melanogaster Meigen at the behavioural and electrophysiological levels. The Shaker locus encodes a variety of A-type potassium channels that are likely to be tissue- and stage specific. Flies containing the different Shaker alleles examined exhibit a variety of defects in their gustatory responses to sucrose, NaCl and KCl. The firing patterns of the labellar chemosensory neurones in response to these stimuli are normal. This suggests that the channels encoded by the Shaker locus are probably not involved in taste transduction, but affect central gustatory circuits. The shaking-B locus affects neuronal connectivity, though its molecular nature is unknown. Mutants at this locus show increased thresholds for detection of sucrose and fructose and lack the attraction response to 0.1 mol l-1 sodium chloride that is exhibited by the wild-type fly. PMID- 1905748 TI - Sensitive competitive-binding ELISAs for quantifying free kappa and lambda light chains in cerebrospinal fluid. AB - Simple, sensitive, and fully standardized solid-phase enzyme-linked competitive binding immunoassays to quantify free kappa and lambda immunoglobulin light chains are described. The assays were developed to measure the concentration of free light chains in cerebrospinal fluid (CSF), in part because elevated levels of free kappa light chains have utility as a diagnostic marker for multiple sclerosis (MS). Polyclonal rabbit antibodies raised against pooled Bence Jones proteins are bound to solid-phase Staphylococcal protein A and used as the primary antisera in this assay. A pool of Bence Jones proteins isolated from the urine of 10 individuals with multiple myeloma are used as a biotin-labeled ligand and to develop a standard curve. The assays as described are sensitive to the low nanogram range and are specific for free kappa or lambda light chains. The assays were found to have acceptable precision, and results correlated highly with concentrations determined using competitive-binding radioimmunoassays previously described. PMID- 1905749 TI - Patient and procedure variables associated with complications following variceal sclerotherapy in children. AB - Variceal sclerotherapy has been performed in the pediatric population, but techniques and dosages of sclerosant recommended in the literature are largely empirical. Having accumulated much data through experience with sclerotherapy in children, we have identified patient and procedure variables associated with early and late complications. We reviewed our experience with 37 pediatric patients, ages 1-18, who underwent 150 sclerotherapy sessions. Sclerotherapy was associated with 12 early complications in 11 patients. Early complications were bleeding (five), respiratory problems (three), false channel formation (two), and gross hematuria (two). Four patients developed strictures. We identified the following variables associated with complications: for bleeding, platelet count less than 100,000/mm3; for respiratory complications and false channel formation, weight less than 12 kg; for false channel formation, dosage of sclerosant/kg/session greater than 1.75 ml/kg; for gross hematuria, total sclerosant/session greater than 20 ml. A need for more than six sclerotherapy sessions for obliteration of varices was associated with a greater frequency of stricture formation. Sclerotherapy can be performed safely in children. Patients less than 12 kg or with platelet counts less than 100,000/mm3 should be monitored carefully for respiratory complications and postprocedure bleeding. Sclerosant dosages greater than 1.75 ml/kg, or 20 ml total sclerosant, should be given with caution. PMID- 1905750 TI - Histologic findings are not correlated with disaccharidase activities in infants with protracted diarrhea. AB - Histologic assessment as well as information about the disaccharidase activity of the small intestinal mucosa can be useful in the management of patients with small intestinal mucosal damage. In an effort to determine whether the degree of small intestinal mucosal damage would be reflected in a corresponding reduction in disaccharidase activity, we compared small intestinal mucosal histology with the results of disaccharidase activity measured in per oral suction small intestinal biopsies obtained from 21 infants with protracted diarrhea. The degree of small intestinal mucosal damage was graded using a subjective score (i.e., 0 to 4+ damage) by a pathologist (P) and by a computer-assisted digitizing system (to assess villus surface area, VSA, and villus/crypt ratio, V/C) in a blinded fashion. The mean (+/- SD) age of the infants was 2.5 +/- 1.5 months, and the duration of diarrhea was 25.2 +/- 11.5 days. There was good correlation between the results obtained from the digitizing system and from the pathologist: VSA versus P, r = 0.695; V/C versus P, r = 0.791; p = 0.0004. All infants demonstrated some degree of small intestinal mucosal damage. The mean (+/- SD) values for P, VSA, and V/C were 2.2 +/- 1.3, 2.9 +/- 0.9, and 0.9 +/- 0.5, respectively. The mean values for lactase, sucrase, and maltase were 17.1 +/- 17.0, 71.1 +/- 54.0, and 224.3 +/- 233 mumol/min/g protein, respectively. No correlation was observed between the histologic scoring results and lactase, sucrase, or maltase measurements. Expressing the disaccharidase activities per unit wet weight of tissue did not improve the correlations. Log transformation of the data also failed to improve the correlations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1905751 TI - The use of cell-free antigens of Paracoccidioides brasiliensis in serological tests. AB - A simple and rapid method for extracting specific cell-free antigens (CFA) from the yeast form of Paracoccidioides brasiliensis grown on agar slants was developed. Extracts were analysed mainly by immunodiffusion (ID) tests, for the immunodiagnosis of paracoccidioidomycosis. Extracts were obtained from 2 to 7-day old cultures. The extract obtained after the third day, which contained 200-300 micrograms of protein/ml, gave the best ID reactions, with 100% sensitivity and specificity. The main precipitation band was intense and showed total identity with that formed by the specific 43 kDa glycoprotein. Other tests such as counterimmunoelectrophoresis and immunoelectrophoresis were also used successfully with CFA. The 3-day CFA extract showed a pattern of polypeptides in the 10-110 kDa range after SDS-polyacrylamide gel electrophoresis. Five components of 20, 43, 45, 55 and 70 kDa reacted on immunoblots with sera from patients with active chronic paracoccidioidomycosis. The specific diagnostic antigen of 43 kDa always predominated in all CFA preparations. The present method is thus very useful for the rapid production of an antigenic extract which can be readily characterized and used in the serodiagnosis of paracoccidioidomycosis. PMID- 1905752 TI - Urea production and recycling in neonates. AB - Urea represents 15% of the nitrogen in breast milk, but its functional significance is unclear. We have proposed that the urea may be utilised as a valuable source of nitrogen in neonates. We report the first measurements of urea kinetics in newborn, full-term infants. Six neonates received a continuous nasogastric infusion of 15N15N-urea over 24 hours. Urine was collected every 2 hours and the isotopic enrichment in urea was measured by mass spectrometry. Urea kinetics were calculated by the method of Jackson. The urea production rate was 17.3 mmol/kg/d (range, 15.6 to 19.2), but the urinary urea excretion rate, 3.5 mmol/kg/d (range, 1.2 to 4.9), was only 20% of production. Hence, 80% of urea produced was hydrolysed in the colon and the nitrogen made available for further metabolism. These data show that urinary urea excretion is a poor indication of urea production in the newborn and that there is substantial salvaging of urea nitrogen by the colon. PMID- 1905753 TI - Partition of energy metabolism in the surgical newborn. AB - Variations in energy expenditure (EE) and substrate utilization were investigated in 12 surgical neonates (body weight, 2.81 +/- 0.15 kg) receiving total parenteral nutrition (TPN) at an energy intake of 66.34 +/- 2.16 kcal/kg/d in a thermoneutral environment of 32 degrees C to 34 degrees C. Respiratory gas exchange was continuously recorded for 12 hours by a computerized, open-circuit indirect calorimeter. Physical activity was monitored on a modified Freymond scale. Urine was collected over 3 days, including the time of the calorimetry study to determine the urinary nitrogen excretion rate. Oxygen consumption, carbon dioxide production, nonprotein respiratory quotient, and EE were calculated according to the principles of indirect calorimetry for each 30-minute period and for the entire 12 hours. During the indirect calorimetry study the patients were receiving a fat-free TPN mixture consisting of 10% glucose and 2% amino acids (GL/AA) for 8 hours. The fat-free TPN was interrupted by an isocaloric and isovolemic infusion of intralipid 10% (IL) for 4 hours. The effect of physical activity on EE was evaluated separately according to the macronutrient intake (GL/AA for 8 hours v IL for 4 hours) and then combined throughout the 12 hours of intravenous alimentation. The neonates were resting during 80% of the 12-hour study time (range, 38% to 90%). The partition of EE expressed as mean +/- SEM in kcal/kg/d was: total EE 48.5 +/- 2.1; resting EE 43.9 +/- 1.6; energy cost of activity 4.6 +/- 1.3.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1905754 TI - Postural sway following inversion sprain of the ankle. AB - The single-limb sway of 20 individuals with a history of unilateral inversion ankle sprain was compared to that of a control group of 30 individuals without a history of ankle sprain. Using a force platform to obtain center-of-pressure data, the linear distance traveled (mm) and the mean power frequency, (Hz) of postural sway were calculated for each subject. The results of this study showed that postural sway amplitude was significantly greater in the injured group than in the control group. Contrary to previous investigations, this study indicates that individuals with a history of inversion ankle sprain are less stable in single-limb stance compared to a noninjured control group. This decreased stability is evident as much as 2 years following the injury. PMID- 1905755 TI - Electrophysiological effects of calcitonin gene-related peptide in bull-frog and guinea-pig atrial myocytes. AB - 1. Electrophysiological effects of calcitonin gene-related peptide (CGRP) on action potentials and corresponding transmembrane currents in single myocytes from bull-frog and guinea-pig atria were studied using a whole-cell voltage-clamp method. 2. CGRP at relatively low concentrations increased the height of the action potential plateau in a dose-dependent manner in both bull-frog and guinea pig myocytes. In addition, in bull-frog cells CGRP accelerated the early phase of repolarization, thus shortening the overall duration of the action potential. In contrast, in guinea-pig myocytes CGRP prolonged the action potential duration at all concentrations that were studied. 3. Voltage-clamp measurements demonstrated that CGRP increased transmembrane calcium current (ICa) in guinea-pig myocytes without a significant change in its voltage dependence. The ED50 value for this effect on ICa was 1.28 +/- 0.55 X 10(-8) M (n = 4). The time course of the inactivation of ICa was not affected by CGRP. 4. CGRP increased the delayed rectifier K+ current (IK) at relatively low concentrations in bull-frog atria, whereas relatively high concentrations were needed to increase IK in guinea-pig myocytes. This effect was observed even after complete inhibition of ICa. 5. CGRP had no significant effect on the inwardly rectifying background K+ current, IK1, even at very high concentrations. 6. Comparison of the time course of ICa augmentation in bull-frog and guinea-pig myocytes revealed an important difference in the effect of CGRP in these two types of cells. CGRP at maximal concentrations increased ICa transiently in bull-frog myocytes, whereas this response was sustained in guinea-pig myocytes. Isoprenaline (Iso) induced sustained increase in ICa in both species. When ICa was fully activated by Iso, CGRP at high concentrations strongly inhibited ICa in the bull-frog, whereas it had little effect on ICa in guinea-pig myocytes. 7. Intracellular application of GTP gamma S (guanosine 5'-O-(3-thiotriphosphate) 10(-4) M) greatly potentiated the CGRP effect on ICa; in contrast, GDP beta S (guanosine 5'-O-(2 thiodiphosphate), 2 x 10(-3) M) partially inhibited the CGRP-induced augmentation of ICa. Taken together, these results indicate that the stimulation of ICa by CGRP is mediated by a GTP-binding protein. 8. The observed dose-dependent changes in ICa and IK in bull-frog and guinea-pig myocytes can explain the different patterns of CGRP-induced changes in action potential shape in these two myocyte preparations. PMID- 1905756 TI - Incorporation of chelator into guinea-pig rods shows that calcium mediates mammalian photoreceptor light adaptation. AB - 1. The effects of steady light on the sensitivity and kinetics of the photocurrent response were studied in the rod photoreceptors of the guinea-pig, using suction pipette recordings of circulating current. 2. The sensitivity of the flash response decreased with increasing background intensity according to Weber's law. Ultimately for the brightest backgrounds saturation ensued. The recovery phase of the flash response was accelerated by steady light, while the early rising phase was little affected. 3. These results indicate that guinea-pig rods adapt to light in much the same way as do the rods and cones of lower vertebrates. 4. The role of cytoplasmic calcium concentration in this adaptation was studied by incorporation of the calcium chelator bis(o-aminophenoxy)ethane- N,N,N',N'-tetraacetic acid (BAPTA) into the rod cytoplasm. Superfusion with a solution containing the membrane-permeant acetoxymethyl ester resulted in progressive changes in the response to light. 5. BAPTA incorporation retarded the falling phase of the flash response, thereby increasing receptor sensitivity, but did not affect the early rising phase of the response. BAPTA also slowed the adaptation of the response to steady illumination. 6. These results indicate that cytoplasmic calcium concentration plays a similar role in the light adaptation of guinea-pig rods to that in the adaptation of the rods and cones of lower vertebrates. Calcium therefore appears to act as the messenger of light adaptation in mammalian rods. PMID- 1905758 TI - Renal artery aneurysm, hypertension and neurofibromatosis. PMID- 1905757 TI - Monoamine oxidase activity in rat and human odontoblasts: a microgasometric study. AB - The microgasometric method was used for determination of MAO activity in single odontoblasts isolated from rat and man. By using tyramine as a substrate, the presence of MAO in these cells was demonstrated. Both molecular forms of MAO, MAO A and MAO B, were found using specific inhibitors clorgyline and deprenyl. PMID- 1905759 TI - Peripheral parenteral nutrition. PMID- 1905760 TI - Streptonigrin and related compounds. 5. Synthesis and evaluation of some isoquinoline analogues. AB - A series of analogues of streptonigrin, in which the quinoline of ring B is replaced by isoquinoline and the substituted pyridine of ring C is replaced by phenyl, nitrophenyl, aminophenyl, or benzyl functions, have been prepared. Thus, 1-substituted isoquinoline-5,8-diones with 7-amino or 6-(alkylamino) groups were prepared. The various quinones were evaluated for antimicrobial activity against Bacillus subtilis and root-growth inhibitory activity against Lepidium sativum. The effect of specific structural changes on these activities was examined with streptonigrin for comparison. The necessity of an aminoquinone function for activity is confirmed. With regard to the antibacterial activity, the isoquinoline analogues appear to be less active compared to the quinoline derivatives. However, the higher degree of antibacterial activity of the 1 benzylisoquinolines and the 1-nitrophenylisoquinolines compared to the 1-phenyl isoquinolines is noteworthy. In contrast to the results seen with the antibacterial activity, most of the isoquinoline analogues showed activity comparable to, or even higher than, that of streptonigrin in the root-growth inhibition assay. The 1-nitrophenylisoquinolines again appear to be the most active. The equal or greater potency of the benzyl analogue in comparison with the phenyl analogue was unexpected and questions the need for the extended conjugation and the geometry required for metal binding as considered earlier. It also opens up new possibilities for structural variation. PMID- 1905762 TI - [Phosphoenolpyruvate:carbohydrate phosphotransferase systems in Enterococcus faecalis]. AB - A wild-type strain of Enterococcus faecalis and its mutants resistant to 2-deoxy D-glucose (2DG) were examined for the presence of phosphoenolpyruvate:carbohydrate phosphotransferase systems (PTSs) with 12 carbohydrates, which were utilized by the organism, as the substrates. The wild type strain possessed a constitutive mannose-PTS, which was reactive with glucose, mannose, glucosamine, 2DG and fructose. This activity was absent in the mutants. No independent glucose- or fructose-PTS was found in the mannose-PTS defective mutants. The mutants, however, showed a low level of a constitutive PTS activity with maltose, suggesting the existence of an independent maltose-PTS in the organism. Both wild-type and mutant strains possessed inducible lactose-, mannitol-, and trehalose-PTSs. Lactose-PTS was induced by either lactose or galactose in the parent, but only by lactose in the mutants. The lactose-PTS was not reactive with galactose, and no separate galactose-PTS was present. These observations suggest that the inducer for lactose-PTS, probably being galactose 6 phosphate, may not be formed from galactose in the organism when the constitutive mannose-PTS is lost by mutation. PMID- 1905763 TI - [Role of active oxygen on the progression of murine lupus nephritis]. AB - In order to study the role of active oxygen radicals on the progression of the immune-complex (IC) nephritis, we administered superoxide dismutase (SOD), catalase (CAT), and dimethylthiourea (DMTU) to (NZB x NZW) F1 mice from 8 weeks of age, 3 times a week. At 40 weeks of age, the urine protein of the control (n = 23) was 11.4 +/- 4.1 mg/day. SOD (n = 12), CAT (n = 6) and SOD + CAT (n = 5) groups were 1.5 +/- 0.4, 25.4 +/- 14.7, 0.7 +/- 0.1 mg/day, respectively. DMTU group (n = 12) showed significantly less proteinuria (0.6 +/- 0.1 mg/day, p less than 0.05) than control. Even if the injection was begun from the late stage of the disease, some effect was observed. Moreover, by DMTU, urinary excretion ratio of PGF1 alpha/TXB2 0.025 +/- 0.003 was higher than control 0.015 +/- 0.001 (p less than 0.05). These findings suggest that oxygen radicals may play an important role during the progression of lupus nephritis. Among the oxygen radical species, hydroxyl radical is considered to be the most pathogenetic factor in IC-mediated nephritis. PMID- 1905764 TI - Transmembrane signalling through G proteins. PMID- 1905761 TI - Changes in sodium-22 turnover and total body potassium in two-kidney, one-clip renovascular hypertension. AB - Changes in sodium-22 turnover and total body potassium (TBK) were studied during acute (within 2 weeks after clipping) and chronic (12-14 weeks after clipping) phases in two-kidney, one-clip (2k, 1c) hypertensive rabbits by using a whole body counter. Sodium-22 injected intravenously was eliminated more rapidly in hypertensive rabbits than in controls. The biological half-life (BHL) of sodium 22 was shorter in hypertensive rabbits during both acute (p less than 0.05) and chronic phases (p less than 0.001). A significant negative correlation was obtained between the BHL of sodium-22 and blood pressure (r = -0.588, p less than 0.05) in hypertensive rabbits. TBK decreased significantly at the chronic phase in hypertensive rabbits (p less than 0.05), while TBK showed no significant change in controls. Serum sodium and potassium did not change during the observation period. Increased plasma aldosterone concentration was observed during the acute phase in hypertensive rabbits. These results suggested that sodium retention was not a major factor in the acute and chronic phases of 2k, 1c hypertension in rabbits and that pressure natriuresis could explain, at least in part, the lack of sodium retention. Furthermore, there appears to be a derangement in the intracellular potassium metabolism which may be associated with the maintenance rather than the development of hypertension. PMID- 1905766 TI - [Immediate results of combined treatment of cancer of the colon using intensive methods of preoperative radiotherapy]. AB - Combined treatment with the use of intensive methods of preoperative radiotherapy was carried out in 41 patients with malignant tumors of the colon. Study of the specific features of the accomplished surgical interventions and the postoperative management of patients showed that short courses of irradiation on a betatron with energy of 25 MeV, given in 5 daily exposures to a total basic dose of 20 Gy or a single exposure to a basic dose of 7.5 Gy had no unfavourable effect on the performance of the operation and the patients' condition in the postoperative period. The immediate results of the operation were found to be good in all patients. PMID- 1905765 TI - Renal tubular arachidonic acid metabolism. PMID- 1905767 TI - Subrenal capsule assay using nude mice as a predictor of the response of the gastric cancer to chemotherapy. AB - Feasibility of utilizing human gastric cancers as first transplant generation xenografts in nude mice for determining tumor sensitivity to chemotherapeutic agents was demonstrated by applying subrenal capsule (SRC) assay. A total of 55 human gastric tumors from patients were tested in this assay. Mitomycin-C (MMC) and hexycarbamyl-5-FU (HCFU, 5-FU derivative) were selected for the treatment of these patients after surgery and also for this assay as first transplant. Evaluable rate of MMC in this assay was 92.7% and that of HCFU was 90.9%. Sensitivity of tumors to MMC was 25% and to HCFU was 32%. Correlation between response to chemotherapy of human tumors in patients and in nude mice was 78.6%. These results indicate that this assay could predict effective drugs for patients with gastric cancer. PMID- 1905768 TI - Intracellular recording from respiratory neurones in the perfused 'in situ' rat brain. AB - The study describes an arterially perfused in situ rat brain preparation, which uses an 'open circuit' flow of blood substitute with or without an oxygen carrier (2% perfluorotributylamine). The respiratory motor output was recorded from the phrenic and hypoglossal nerves, and could be maintained for up to 11 h from the start of perfusion (temperature of perfusate: 27-30 degrees C). The preparation allowed stable intracellular recordings from respiratory neurons in the brain stem and cervical spinal cord, and should be suitable for other studies which cannot be performed in standard whole animal models. The advantages of this approach compared with other in vitro or perfused in situ preparations are discussed. PMID- 1905769 TI - A tandem-lens epifluorescence macroscope: hundred-fold brightness advantage for wide-field imaging. AB - The design of a macroscope constructed with photography lenses is described and several applications are demonstrated. The macroscope incorporates epi illumination, a 0.4 numerical aperture, and a 40 mm working distance for imaging wide fields in the range of 1.5-20 mm in diameter. At magnifications of 1X to 2.5X, fluorescence images acquired with the macroscope were 100-700 times brighter than those obtained with commercial microscope objectives at similar magnifications. In several biological applications, the improved light collection efficiency (20-fold, typical) not only minimized bleaching effects, but, in concert with improved illumination throughput (15-fold, typical), significantly enhanced object visibility as well. Reduced phototoxicity and increased signal-to noise ratios were observed in the in vivo real-time optical imaging of cortical activity using voltage-sensitive dyes. Furthermore, the macroscope has a depth of field which is 5-10 times thinner than that of a conventional low-power microscope. This shallow depth of field has facilitated the imaging of cortical architecture based on activity-dependent intrinsic cortical signals in the living primate brain. In these reflection measurements large artifacts from the surface blood vessels, which were observed with conventional lenses, were eliminated with the macroscope. PMID- 1905770 TI - Hyperglycemic properties of serotonin receptor antagonists. AB - Several serotonin (5-HT) receptor antagonists with varying specificities for the 5-HT receptor types, were studied with regard to their effects on blood glucose levels in mice. The non-selective antagonists, metergoline and methysergide, proved to be hyperglycemic at doses commonly used to antagonize 5-HT receptors. In contrast, ritanserin (a 5-HT2 and 5-HT1c antagonist) and MDL 72222 (a 5-HT3 antagonist) were effective only at doses which surpassed the dose range considered to be selective for their respective receptors. The results suggest that 5-HT systems play a role in maintaining glucose homeostasis and that 5-HT1 receptors may be particularly important in this function. Furthermore, the inherent hyperglycemic properties of non-selective serotonin antagonists described here, are pertinent to studies using these agents to investigate glucose metabolism. PMID- 1905772 TI - Naloxone application to the ventrolateral medulla enhances the respiratory response to inspired carbon dioxide. AB - Previous studies have shown that systemic administration of the opiate antagonist naloxone potentiates the ventilatory response to inspired carbon dioxide. The present study was designed to localize the site of action of naloxone for increasing the respiratory chemosensitivity to inhaled carbon dioxide (CO2) in cats. Naloxone applied topically to the caudal chemosensitive area on the ventral medullary surface (VMS) during hypercapnic breathing produced a 75% greater increase in minute ventilation than hypercapnic breathing alone. Furthermore, hypercapnic breathing produced a 200% increase in neuronal activity of VMS chemosensitive cells; this was further increased 120% by naloxone. It is concluded that naloxone increases the sensitivity of neurons in the caudal respiratory chemosensitive area of cats to hypercapnia, and that endogenous opiates may act as modulators at VMS chemosensitive sites during hypercapnic breathing. PMID- 1905771 TI - Effect of 6-hydroxydopamine on murine hematopoietic stem cells: enhanced cytotoxicity on megakaryocyte colony forming units. AB - We examined the effect of catecholaminergic neurotoxin 6-hydroxydopamine (6-OHDA) on murine committed megakaryocyte progenitor cells, the megakaryocyte-colony forming unit (CFU-Meg). More mature cells of the megakaryocyte series have the capacity for active uptake of catecholamines, and we speculated that the CFU-Meg would also take up 6-OHDA and be selectively killed. CFU-Meg were much more sensitive to the effects of this agent than were granulocyte-macrophage colony forming units (CFU-GM) or spleen-colony forming units. Co-incubation with catalase, which would destroy hydrogen peroxide generated extracellularly by the autoxidation of 6-OHDA, ablated 6-OHDA toxicity towards CFU-GM, but also significantly reduced the effect on CFU-Meg. Mazindol, a selective dopamine uptake inhibitor did not alter 6-OHDA effect on either CFU-Meg or CFU-GM. Finally, CFU-Meg were no more sensitive to incubation with hydrogen peroxide than were CFU-GM. These data suggest that CFU-Meg, unlike their more mature progeny, do not actively concentrate 6-OHDA, and the excess toxicity of this agent towards CFU-Meg is probably due to increased sensitivity to autoxidation products of 6 OHDA, other than hydrogen peroxide, generated extracellularly. PMID- 1905773 TI - Assays for lupus anticoagulant: the sensitivity of different assays. AB - Fifty patients with systemic lupus erythematosus were studied for the presence of lupus anticoagulant using three different assays--kaolin clotting time, platelet neutralization test, and tissue thromboplastin inhibition test. Lupus anticoagulant could be detected in seven cases (14%) with the use of one test in cases with a partial prothrombin time with kaolin more than five seconds greater than normal. The detection rate rose to 20% (10 cases) when using all three tests, so a panel of three assays could identify lupus patients apparently at risk for thrombotic complications. PMID- 1905774 TI - EDTA, the traditional anticoagulant of haematology: with increased automation is it time for a review? PMID- 1905775 TI - Detection of cannabinoids in urine: a cost-effective low risk immunoassay procedure. AB - Using Syva EMIT reagents and a Cobas Bio centrifugal analyser we have developed a cost-effective assay for the detection of cannabinoids in urine. With this method, up to 1500 samples can be assayed with a single 100 test kit while maintaining acceptable precision. A mean CV of 6.1% was obtained for the concentration range 80-130 micrograms/l. The method is suitable for high-risk urines since heart treatment may be performed prior to analysis. There was no significant change in the measured concentration of cannabinoids in urine samples on storage in plastic containers, refrigerated or frozen, for up to seven weeks. PMID- 1905776 TI - Hepatic transport of the magnetic resonance imaging contrast agent Fe(III)-N-(3 phenylglutaryl)desferrioxamine B. AB - We have studied the hepatic transport of Fe(III)-N-(3 phenylglutaryl)desferrioxamine B (Fe-PGDF). Using 59Fe-PGDF in biliary cannulated rats we have shown that 32 +/- 2% of an iv bolus dose was excreted into the bile. In animals pretreated with a saturating dose of taurocholate, oxyphenonium, or bromosulfophthalein (BSP), 25 +/- 6%, 23 +/- 1%, or 1.6 +/- 0.8% of the dose, respectively, was excreted into the bile. Magnetic resonance images indicated that BSP blocked uptake of Fe-PGDF by the hepatocytes. Possible enterohepatic recycling of 59Fe-PGDF was investigated in linked rat experiments. All of the material excreted into the bile of the donor, 28 +/- 10% of the dose, was recovered in the gastrointestinal tract of the recipient, but none was found in its bile or urine. These results suggested that uptake of Fe-PGDF by the hepatocytes occurred via the BSP transporter and that no enterohepatic recycling of the contrast agent occurred. PMID- 1905778 TI - Implication of thromboxane in the pathogenesis of Kawasaki disease and a suggestion for using novel thromboxane synthetase inhibitors in its treatment. AB - Kawasaki disease, a mucocutaneous lymph node syndrome predominantly prevalent in children, presents with coronary artery aneurysms and thrombocytosis, and investigators have suggested use of anticoagulants in addition to platelet inhibiting drugs. In Kawasaki disease, hypersensitivity reactions due to antigen/antibody complexes (Arthus type III) may damage the vessel wall and induce arteritis, and antigens may be of microbial or viral origin. Since thromboxane has been implicated in the pathogenesis of Kawasaki disease, I suggest use of ginger and carbon dioxide, novel thromboxane synthetase inhibitors. Thromboxane synthetase inhibitors may act as anticoagulants, platelet inhibitors, anti-inflammatory agents, and agents with both antimicrobial and antiviral activity. PMID- 1905779 TI - Neonatal continuous insulin infusion: a survey of ten level III nurseries in Los Angeles county. PMID- 1905777 TI - Analysis of 23Na NMR spectra from isolated perfused hearts. AB - The 23Na NMR spectra obtained from isolated hearts perfused with buffer containing the paramagnetic shift reagent dysprosium triethylenetetraminehexaacetic acid, Dy(TTHA)3-, are complex and contain a number of overlapping peaks of different intensities. Spectra from rat, rabbit, guinea pig, and ferret hearts obtained during periods of control perfusion are similar and undergo similar changes when the hearts are subjected to periods of ischemia and reflow. The contributions from the intracellular, interstitial, vascular, and bath compartments to the multiple peaks in the spectra of rats hearts have been assigned. The significant contributions to these spectra of bulk magnetic susceptibility effects and incomplete mixing have been demonstrated through a series of modeling experiments. Since the spectra from hearts of different species are so similar, the peak assignments made for the rat are applicable to spectra from rabbit, guinea pig, and ferret hearts as well. This work provides a framework for quantitative analysis of the spectral changes which occur during conditions such as ischemia and reflow. PMID- 1905780 TI - Bacterial growth in iced and noniced formula for feeding premature infants: a pilot study. PMID- 1905781 TI - Relative contributions of MCM1 and STE12 to transcriptional activation of a- and alpha-specific genes from Saccharomyces cerevisiae. AB - We have examined the relative contributions of MCM1 and STE12 to the transcription of the a-specific STE2 gene by using a 367 bp fragment from the STE2 5'-noncoding region to drive expression of a reporter lacZ gene. Mutation of the MCM1 binding site destroyed MCM1.alpha 2-mediated repression in alpha cells and dramatically reduced expression in a cells. The residual expression was highly stimulated by exposure of cells to pheromone. Likewise, the loss of STE12 function reduced lacZ expression driven by the wild-type STE2 fragment. In the absence of both MCM1 and STE12 functions, no residual expression was observed. Thus, the STE2 fragment appears to contain two distinct upstream activation sequences (UASs), one that is responsible for the majority of expression in cells not stimulated by pheromone, and one that is responsible for increased expression upon pheromone stimulation. In further support of this idea, a chemically synthesized version of the STE2 MCM1 binding site had UAS activity, but the activity was neither stimulated by pheromone nor reduced in ste12 mutants. Although transcription of alpha-specific genes also requires both MCM1 and STE12, these genes differ from a-specific genes in that they have a single, MCM1 dependent UAS system. The activity of the minimal 26 bp UAS from the alpha specific STE3 gene was both stimulated by pheromone and reduced in ste12 mutants. These data suggest that at alpha-specific genes STE12 and MCM1 exert their effects through a single UAS. PMID- 1905782 TI - The indoleacetic acid-lysine synthetase gene of Pseudomonas syringae subsp. savastanoi induces developmental alterations in transgenic tobacco and potato plants. AB - The iaaL gene of Pseudomonas syringae subsp. savastanoi encodes an indoleacetic acid-lysine synthetase that conjugates lysine to indoleacetic acid. A chimaeric gene consisting of the iaaL coding region under the control of the 35S RNA promoter from cauliflower mosaic virus (35SiaaL) has been used to test if iaaL gene expression leads to morphological alterations in tobacco and potato. Transgenic tobacco plantlets bearing this construct have been shown to synthesize IAA-[14C]lysine when fed with [14C]lysine. In late stages of development, their leaves show an increased nastic curvature (epinasty) of the petiole and midvein, a finding suggestive of an abnormal auxin metabolism. The alteration is transmitted to progeny as a dominant Mendelian trait cosegregating with the kanamycin resistance marker. Transgenic potato plants harbouring the construct are also characterized by petiole epinasty. Moreover, 35SiaaL transgenic plants have an increased internode length in potato and decreased root growth in both tobacco and potato. An increased content of IAA-conjugates in leaf blade was found to correlate with the epinastic alterations caused by iaaL gene expression in tobacco leaves. These data provide evidence that IAA conjugation is able to modulate hormone action, suggesting that the widespread endogenous auxin conjugating activities are of physiological importance. PMID- 1905783 TI - Immunoglobulin VH genes of the goldfish, Carassius auratus: a re-examination. AB - Five VH-related genomic sequences from the goldfish, Carassius auratus, have been characterized. One of these sequences appeared to be a functional gene, and four to be pseudogenes. The main conclusions drawn from this study were that: (1) With minor exceptions, goldfish VH genes conform to the typical pattern of vertebrate VH genes in terms of their structure (they encode an intron-split hydrophobic leader, 3 framework and 2 complementarity-determining regions, and possess a typical 3' recombination signal sequence for VH to D joining) and regulatory sequences (possession of a typical upstream octameric promoter). (2) The sequences indicate that goldfish possess multiple families of VH sequences (at least three). Two of these families contain approximately 6 and 10 members, as judged from Southern blot hybridization experiments. (3) Goldfish VH gene families are distributed throughout the members of the species in the manner typical of that of VH families in other vertebrate species. Thus, this observation corrects the previous conclusion (Wilson et al., Proc. natn. Acad. Sci. U.S.A. 85, 1566-1570, 1988) that VH genes are discontinuously distributed in the goldfish population. PMID- 1905784 TI - A possible procedure for reducing the immunogenicity of antibody variable domains while preserving their ligand-binding properties. AB - It is proposed to reduce the immunogenicity of allogeneic antibody variable domains, while preserving ligand-binding properties, by reducing their antigenicity through replacement of the exposed residues in the framework regions which differ from those usually found in host antibodies. The results of a comparison of representative murine antibody sequences with those of human origin suggest that the number of residues that need to be replaced to "humanize" those antibodies could be small. PMID- 1905785 TI - Analysis of a whistle-blowing: the Imanishi-Kari affair. PMID- 1905786 TI - Acquired immunity and epidemiology of Schistosoma haematobium. AB - Human immune responses to schistosome infection have been characterized in detail. But there has been controversy over the relative importance of ecological factors (variation in exposure to infection) and immunological factors (acquired immunity) in determining the relationships between levels of infection and age typically found in areas where infection is endemic. Independent effects of exposure and age on the rates of reinfection with Schistosoma haematobium after chemotherapy have been demonstrated in the Gambia and Zimbabwe. This age effect could be the result of acquired immunity to infection. Indeed, allowing for variation in exposure and age, low rates of reinfection in the Gambia are correlated with high amounts of specific IgE antibodies--human IgE can kill S. mansoni schistosomulae in vitro. Further, animals can acquire immunologically mediated resistance to S. mansoni infection, although nonimmunological factors could also be involved. Acquisition of this immunity seems to be related to the cumulative effects of repeated infection and provides only partial protection. These characteristics are consistent with immuno-epidemiological data for both S. mansoni and S. haematobium infections of humans. We have now analysed age prevalence data for human infection with S. haematobium, and find patterns of variation that are indeed consistent with the epidemiological effects of acquired immunity predicted by mathematical models. PMID- 1905787 TI - Quantitative autoradiographic study of the postnatal development of adenosine A1 receptors and their coupling to G proteins in the rat brain. AB - Adenosine is now considered as a major regulatory agent in the mammalian central nervous system. Its actions are mediated by specific receptors which are coupled with an adenylate cyclase system via a G protein. The postnatal development of adenosine A1 receptors was studied by quantitative autoradiography using [3H]N6 cyclohexyladenosine, a potent receptor agonist in 42 rat brain structures. The coupling of these sites to G proteins was examined by measuring the effects of in vitro addition of guanylyl-5'-imidodiphosphate, a stable analogue of guanosine triphosphate, on N6-cyclohexyladenosine binding. [3H]N6-Cyclohexyladenosine specific binding was quite low at birth, around 10% of adult levels, and exhibited a rather homogeneous distribution pattern, except in thalamic nuclei. Data showed a sequential development of adenosine A1 receptors in relation to the time course of maturation of cerebral structures with a proliferation peak which paralleled rapid brain growth. The time period by which adult levels are reached differed according to the cerebral region studied. N6-Cyclohexyladenosine specific binding sites appeared to be functionally linked to G proteins in all structures and at all postnatal stages. However, the potency of guanylyl-5' imidodiphosphate to displace N6-cyclohexyladenosine binding was significantly lower before 5 days of age, suggesting functional changes during postnatal maturation in cerebral pathways modulated by adenosine. PMID- 1905788 TI - Differential effects of chronic ethanol consumptions or thiamine deficiency on spatial working memory in Balb/c mice: a behavioral and neuroanatomical study. AB - This study was aimed to compare the effects of either a thiamine deficiency or a chronic ethanol consumption on memory and on neuronal density within the median mammillary nucleus. Results showed that alcohol-treated (48 weeks) mice exhibited a behavioral impairment in a sequential alternation task characterized by a progressive decay of alternation rates as a function of the number of trials; such a deficit was not observed in controls and thiamine-deficient subjects. A quantitative analysis using histological sections showed an important reduction of neuronal density within the mammillary bodies following the alcohol treatment but not following thiamine deficiency. PMID- 1905789 TI - Endothelin induces a sustained rise in intracellular calcium in hippocampal astrocytes. AB - We report that the endothelins, a newly described family of vasoactive peptides, have a profound effect on intracellular calcium levels of cultured rat hippocampal astrocytes that resembles the effect of endothelin (ET) on vascular smooth muscle cells (VSMCs) in many respects. The astrocyte's response has two components that can be distinguished by their extracellular calcium requirement and time course. Within seconds of application, ET induces a transient calcium spike that corresponds to a release of calcium from internal stores. The second component follows immediately, is dependent upon extracellular calcium, and maintains an elevated intracellular calcium level for many minutes. Sustained elevations of intracellular calcium can dramatically alter astrocyte morphology and induce cell division in many other cell types. ET may serve these functions, and thus form a communication link between blood vessels and neurons through astrocytes. PMID- 1905790 TI - Enteral tube feeding: a clinical perspective on recent advances. PMID- 1905791 TI - The employee-safety and infection-control manual: guidelines for the ambulatory health care center. AB - The ambulatory health care center has an empirical need to maintain adequate policies and procedures designed to safeguard the health and physical safety of both clients and employees. Of particular concern is the health care worker's risk of injury or exposure to infection. This article discusses the development of a comprehensive employee-safety and infection-control manual. Such a manual can assist in the accreditation of an ambulatory health care center by a national accrediting organization, and can also serve as a risk-management tool. An example of a manual's table of contents, a specific policy/procedure, a waiver form regarding human immunodeficiency virus exposure, and a hepatitis B virus "vaccination status" form are provided. Additionally, two "quick-look" texts are presented as examples of fast reference guides for common safety practices and the treatment of the employee with a health-threatening exposure. PMID- 1905792 TI - Health promotion and disease prevention for the international traveler. AB - International travel is becoming increasingly popular with Americans, whether for business or pleasure. Approximately 10 to 15 million U.S. citizens travel abroad each year, and more than 8 million of these travel to developing nations. Travelers risk exposure to viral, bacterial and parasitic diseases not often encountered in the United States. Clients planning an international journey should be encouraged to obtain advice from their primary care practitioner. This article reviews the health care needs of the international traveler, including predeparture evaluation, required and recommended immunizations, and advice on disease-prevention measures. PMID- 1905793 TI - Immunohistolocalization of the carbonic anhydrase isozymes I, II and III in equine salivary glands. AB - The immunolocalization of carbonic anhydrase isozymes in equine salivary glands was investigated for assessment of their biologic functions. In parotid glands, duct segments showed reactivity with CA-I and CA-III. CA-III was selectively located in duct segments, particularly in the basal cells of the interlobular duct. Serous acinar cells were positive for CA-I and CA-II. In submandibular glands, CA-I and CA-II were present in serous demilune and duct segments. CA-II was selectively located in the duct segments, as also noted in the parotid gland. In sublingual glands, CA-I and CA-II were located in serous demilune, as also in the case of the submandibular gland. In the duct segments, all the isozymes considered in this study were found to be present. PMID- 1905794 TI - Meningocele or gliomatosis? PMID- 1905795 TI - On the pathogenesis of diabetic retinopathy. A 1990 update. AB - Although most investigators now agree that chronic hyperglycemia is the basis for diabetic retinopathy, this has not been proven definitively. Even if chronic hyperglycemia is the initial common pathway leading to retinopathy and other complications of diabetes, it appears to act by different mechanisms in different tissues. The enzyme, aldose reductase, may play a major role in the development of diabetic retinopathy, but contradictory evidence exists. At the present time, results of the only study of aldose reductase inhibition and diabetic retinopathy reported in humans were negative. Another mechanism worthy of consideration is nonenzymatic glycation (glycosylation) of proteins, but there is no direct evidence of a causal role in diabetic retinopathy. Several growth factors have been identified in the retina that may promote neovascularization, and at least two inhibitors may prevent the process. There is evidence to support a role for basic and, perhaps, acidic fibroblast growth factors in retinal vasoproliferation. Transforming growth-factor beta, a peptide produced by capillary pericytes and smooth muscle cells and activated by the interaction of these cells with vascular endothelial cells, appears to be an important inhibitor of neovascularization, as is the vascular basement membrane. PMID- 1905797 TI - Carbon dioxide laser surgery of oral leukoplakia. AB - Oral leukoplakia is a precancerous lesion of the oral mucosa. The risk of malignant transformation depends on the clinical and histologic classification and the location of the lesion. For a nonhomogeneous leukoplakia, this risk is 23.4% to 38.0%. In the presence of epithelial dysplasia, the possibility of malignant transformation is 36.3% to 43.0%. Leukoplakia is limited to the epithelium, so a selective removal of this part of the mucosa seems to be the best preventive treatment. Carbon dioxide laser surgery accomplishes a superficial removal by evaporation. A total of 70 patients with 103 oral leukoplakias were treated with carbon dioxide laser evaporation. This resulted in an excellent wound healing with virtually no scarring. The patients were followed up during a period of up to 12 years (mean 5.3 years), showing a cure rate of 90%. PMID- 1905796 TI - Antiretinal antibodies in serum of patients with age-related macular degeneration. AB - Antibodies, immunoreactive with normal human retinal proteins, were detected by Western immunoblot analysis in the sera of 30 patients with age-related macular degeneration (AMD). Sera from 14 of these patients demonstrated positive binding predominantly to a doublet protein of molecular weight between 58 and 62 kD. The sera from the remaining 16 patients and from 12 control subjects reacted either weakly or not at all with the doublet protein. No correlation was found with any specific type of AMD. The serum antibodies also immunocrossreacted with the same proteins from isolated photoreceptor outer segments; this was confirmed by indirect immunofluorescence on intact retinas. The crossreactivity of the serum antibodies with a protein of Mr 58 to 62 kD, the lower band present in the bovine purified neurofilament-68 kD preparation, suggests strongly that this protein may be a component of the neuronal cytoskeleton. However, it is not clear whether these autoantibodies play a direct role in the etiology of AMD or represent a nonspecific response to retinal damage. PMID- 1905798 TI - The evolution of the interstitial infiltrate in rejecting rat renal allografts: with particular reference to the production of gamma-interferon. AB - This study aimed to examine the evolution of the leucocytic infiltrate in rat renal allografts in the first 5 days of rejection. Immunohistology was used to assess the absolute numbers of infiltrating leucocytes in the rejecting allografts. The total infiltrate approximately doubled daily from day 1 through to day 4 (370 +/- 15 total leucocytes/mm2 of tissue on day 1 vs 5055 +/- 135 on day 4, p less than 0.05 for all days) and increased only a minor degree on day 5 (5485 +/- 535 leucocytes/mm2, p = n.s.). CD4 positive cells predominated until day 3, after which time CD8 positive cells greatly outnumbered CD4 positive cells (CD4:CD8 ratio day 3 1.83 vs day 5 0.53, p less than 0.05). Gamma-interferon was positive in T cells on day 2 (73% of all T cells) and was slightly positive on day 3 (5% of all T cells) but was negative on days 4 and 5. Activation markers such as IL-2Rs increased markedly from day 3. These findings favour a pivotal role for CD4 positive cells in the early phase of rejection and suggest that the early release of lymphokines by these cells is associated with the recruitment of CD8 positive cells to the allograft and the activation of those leucocytes present. PMID- 1905799 TI - Immediate vs. delayed treatment of group A beta-hemolytic streptococcal pharyngitis with penicillin V. AB - Three hundred six children with probable Group A beta-hemolytic streptococcal pharyngitis were enrolled in a randomized double blind trial to compare the effects of immediate vs. delayed treatment with oral penicillin V. Among the 229 culture-positive patients, 111 were randomly assigned to receive penicillin V immediately and 118 to receive a placebo for 48 to 52 hours followed by penicillin V. Patients were evaluated clinically for 48 to 52 hours following initiation of treatment. The Streptozyme test was used to measure acute to convalescent antibody titer. Both regimens resulted in a greater than 92% cure rate. Early treatment was associated with significantly fewer and milder signs and symptoms on Day 3 and a significantly lower rise in the antibody titer. On the other hand we found 8 (7%) relapses and 18 (16%) early and 14 (13%) late recurrences in this group; all were significantly higher than the corresponding numbers of 2 (2%), 6 (5%) and 4 (3%), respectively, in the late treatment group. This study shows the beneficial effect of early treatment with penicillin V on the clinical course of Group A beta-hemolytic streptococcal pharyngitis. This study also shows that delayed penicillin treatment may be associated with a lower incidence of subsequent Group A beta-hemolytic streptococcal pharyngitis. PMID- 1905800 TI - Hepatic abscess caused by a ventriculoperitoneal shunt. PMID- 1905801 TI - Eukaryotic start and stop translation sites. AB - Sequences flanking translational initiation and termination sites have been compiled and statistically analyzed for various eukaryotic taxonomic groups. A few key similarities between taxonomic groups support conserved mechanisms of initiation and termination. However, a high degree of sequence variation at these sites within and between various eukaryotic groups suggest that translation may be modulated for many mRNAs. Multipositional analysis of di-, tri-, and quadrinucleotide sequences flanking start/stop sites indicate significant biases. In particular, strong tri-nucleotide biases are observed at the -3, -2, and -1 positions upstream of the start codon. These biases and the interspecific variation in nucleotide preferences at these three positions have lead us to propose a revised model of the interaction of the 18S ribosomal RNA with the mRNA at the site of translation initiation. Unusually strong biases against the CG dinucleotide immediately downstream of termination codons suggest that they may lead to faulty termination and/or failure of the ribosome to disassociate from the mRNA. PMID- 1905802 TI - The impact of two-dimensional pulsed-field gel electrophoresis techniques for the consistent and complete mapping of bacterial genomes: refined physical map of Pseudomonas aeruginosa PAO. AB - The SpeI/DpnI map of the 5.9 Mb Pseudomonas aeruginosa PAO (DSM 1707) genome was refined by two-dimensional (2D) pulsed-field gel electrophoresis techniques (PFGE) which allow the complete and consistent physical mapping of any bacterial genome of interest. Single restriction digests were repetitively separated by PFGE employing different pulse times and ramps in order to detect all bands with optimum resolution. Fragment order was evaluated from the pattern of 2D PFGE gels: 1. Partial-complete digestion. A partial restriction digest was separated in the first dimension, redigested to completion, and subsequently perpendicularly resolved in the second dimension. 2D-gel comparisons of the ethidium bromide stain of all fragments and of the autoradiogram of end-labeled partial digestion fragments was nearly sufficient for the construction of the macrorestriction map. 2. Reciprocal gels. A complete restriction digest with enzyme A was run in the first dimension, redigested with enzyme B, and separated in the second orthogonal direction. The order of restriction digests was reverse on the second gel. In case of two rare-cutters, fragments were visualized by ethidium bromide staining or hybridization with genomic DNA. If a frequent and a rare cutter were employed, linking fragments were identified by end-labeling of the first digest. 3. A few small fragments were isolated by preparative PFGE and used as a probe for Southern analysis.--38 SpeI and 15 DpnI fragments were positioned on the map. The zero point was relocated to the 'origin of replication'. The anonymous mapping techniques described herein are unbiased by repetitive DNA, unclonable genomic regions, unfavourable location of restriction sites, or cloning artifacts as frequently encountered in other top-down or bottom up approaches. PMID- 1905803 TI - Camptothecin cytotoxicity in mammalian cells is associated with the induction of persistent double strand breaks in replicating DNA. AB - Camptothecin is a specific topoisomerase I poison and is highly cytotoxic to eukaryotic cells. In the present study, we show, using a pulse field gel electrophoresis assay, that camptothecin induces DNA double strand breaks (DSBs) specifically in newly replicated DNA. Camptothecin induces these replication associated DNA DSBs in a dose-dependent manner. At levels of the drug which are toxic to the cell, these breaks are long-lived, and still measurable 24 hr after treatment. Both camptothecin induced DSBs and cytotoxicity are prevented by co exposure with aphidicolin--a result which indicates that ongoing DNA synthesis is required for the production of DNA DSBs and cell killing. It has been proposed that camptothecin toxicity involves an interaction between the replication machinery and a drug-mediated topoisomerase I-DNA cleavable complex. The present work indicates, for the first time in mammalian cellular DNA, that one possible outcome of this interaction is a replication-associated DSB, a lesion which is likely to be highly cytotoxic. PMID- 1905806 TI - Premenstrual syndrome. Tailoring treatment to symptoms. AB - Despite the interest in premenstrual syndrome (PMS) taken by the media and the public in recent years, some women still do not recognize the cyclic nature of their symptoms. Thus, PMS continues to elude diagnosis. Dr Nader discusses the major categories of symptoms and when they occur, summarizes theories on the cause of PMS, and comments on how well these theories have been substantiated by testing. Choosing agents for treatment on the basis of symptoms to be controlled is also described. PMID- 1905804 TI - A labile repressor acts through the NFkB-like binding sites of the human urokinase gene. AB - Transcription of the human urokinase type plasminogen activator (uPA) gene in HeLa cells is induced by phorbol myristate acetate (PMA), interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF alpha). The response to these factors is rapid, independent of new protein synthesis and amplified in the presence of an inhibitor of protein synthesis, indicating the presence of a labile repressor. A DNA element, similar to the binding site for the transcription factor NFkB, is located around--1865 with respect to the start site of transcription in the uPA promoter and confers superinducibility by these agents in the presence of cycloheximide (CHX). A synthetic copy of this element confers superinducibility on a minimal uPA gene promoter and on the thymidine kinase (TK) gene promoter linked to the chloramphenicol acetyl transferase (CAT) gene. CHX alone does not increase transcription from these constructs in HeLa cells, although it superinduces the effects of PMA, IL-1 and TNF alpha. A second NFkB-like binding site located at around--1835 is not capable of conferring transcriptional activation under the same conditions. Our results suggest that maximal transcriptional activation of the uPA gene by PMA, IL-1 and TNF alpha requires the induction of NFkB activity and the decay of a short lived repressor protein, possibly IkB. PMID- 1905805 TI - Nucleotide sequence of ermFU, a macrolide-lincosamide-streptogramin (MLS) resistance gene encoding an RNA methylase from the conjugal element of Bacteroides fragilis V503. PMID- 1905807 TI - Treating the progressive stages of Parkinson's disease. AB - Parkinson's disease affects thousands of Americans, men and women equally and apparently with little regard to race. Its diagnosis depends largely on repeated clinical observations of representative signs, such as resting tremor, rigidity, bradykinesia, and gait disturbances. Patients progress through stages: Early disease involves only one limb or side and confers minimal disability, but advanced disease restricts patients to full care. Treatment is chosen on the basis of disease stage and patient response. Combination carbidopa-levodopa (Sinemet) is appropriate for any significant degree of disability, and other antiparkinsonian drugs and anticholinergic agents may be used as adjuncts. Electroconvulsive therapy, use of selegiline hydrochloride (Eldepryl), and surgery are still undergoing investigation but may hold promise. PMID- 1905808 TI - Simvastatin but not pravastatin inhibits the proliferation of rat aorta myocytes. AB - The in vitro effect of simvastatin and pravastatin, two competitive inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, on the proliferation of rat aortic smooth muscle cells was investigated. Simvastatin, but not pravastatin, inhibited the replication of arterial myocytes in concentrations ranging between 0.01 microM and 10 microM. The inhibition, evaluated as cell number and nuclear incorporation of [3H]thymidine, was dose-dependent and completely prevented by addition of mevalonate (100 microM), confirming the role of mevalonate or its products in regulating cell division and growth. The present results provide evidence that simvastatin, in addition to its effect on cholesterol biosynthesis, interferes in vitro with other processes involved in atherogenesis. PMID- 1905809 TI - Nitroglycerin absorption from transdermal systems: formulation effects and metabolite concentrations. AB - We recently compared plasma concentrations of nitroglycerin and its two dinitrate metabolites in 16 healthy male subjects after application of two controlled release transdermal formulations of the drug. Analysis of the resulting plasma concentration-time curves indicated that the two formulations did not produce equivalent concentrations of parent drug or either of the dinitrate metabolites during the initial period of dosing. In addition, both formulations produced concentrations of the two dinitrate metabolites that exceeded the concentration of the parent drug by severalfold. Even if the pharmacologic effect of the dinitrate metabolites is low compared to that of nitroglycerin, these higher concentrations may contribute to the effect of nitroglycerin. Scrutiny of the ratio of 1,2-glyceryl dinitrate to 1,3-glyceryl dinitrate in the 16 subjects confirmed previous observations that preferential formation of the 1,2-glycerol dinitrate metabolite may occur depending on the route of administration. This ratio may thus be indicative of the bioavailability of nitroglycerin following transdermal application. Additional data suggesting racial differences in nitroglycerin absorption after transdermal application are presented. PMID- 1905810 TI - Pharmacokinetics of once-a-month injectable microspheres of leuprolide acetate. AB - The pharmacokinetic parameters of leuprolide acetate, a potent analogue of LH-RH, were determined in rats and dogs after i.v. and s.c. dosing with leuprolide solution. The effective human dose of once-a-month injectable microspheres of leuprolide was estimated to be about 3.2 to 8.1 mg analogue/month using these parameters. After microsphere injection at three different doses in rat serum leuprolide concentrations were sustained for over 4 weeks, and the AUCs and mean serum levels were linearly correlated with the dose. The serum levels and urinary excretion of the analogue in rats after repeated s.c. injection of the microspheres every 4 weeks exhibited similar profiles after each injection; no changes of the absorption and excretion of the analogue after the repeated injection could be demonstrated. The serum levels of the analogue metabolite (M I) were 21% of the intact form 3 hr after injection of the microspheres but very low at the steady state after 1 to 4 weeks. PMID- 1905811 TI - Mutation and selection during the secondary response to 2-phenyloxazolone. AB - The most characteristic feature of the mouse antibody response to the hapten 2 phenyloxazolone is the recurrent expression of the light-chain variable region Igk-VO chi 1 gene in its germ-line or mutated configuration. The analysis of somatic mutants of the Igk-VO chi 1 gene reported here indicates that, as found during the primary response, hypermutation is also activated during the secondary response. Somatic mutations in the Igk-VO chi 1 gene increased in sequences obtained at day 14 and day 21 in the primary response and again in the secondary response at days 3, 5, and 7. The ratio of replacement to silent mutations also increased, particularly between days 5 and 7, suggesting that a stage of negative selection operates on new somatic mutants generated in the secondary response. Most Igk-VO chi 1 mutants isolated in the secondary response had the features of selected memory clones (i.e., they carried mutations known to increase binding affinity for the hapten). However, some clones had chain-termination codons, and others had mutations predicting a nonfunctional light chain. At least three and possibly five of these clones also expressed the mutation characteristic of the memory response to 2-phenyloxazolone (His-34----Asn-34/Gln-34). We conclude that after a second antigenic challenge, new somatic variants, including some leading to the loss of antigen binding, are generated by hypermutation of cells derived from the memory pool. PMID- 1905812 TI - G alpha 12 and G alpha 13 subunits define a fourth class of G protein alpha subunits. AB - Heterotrimeric guanine nucleotide-binding regulatory proteins (G proteins) are central to the signaling processes of multicellular organisms. We have explored the diversity of the G protein subunits in mammals and found evidence for a large family of genes that encode the alpha subunits. Amino acid sequence comparisons show that the different alpha subunits fall into at least three classes. These classes have been conserved in animals separated by considerable evolutionary distances; they are present in mammals, Drosophila, and nematodes. We have now obtained cDNA clones encoding two murine alpha subunits, G alpha 12 and G alpha 13, that define a fourth class. The translation products are predicted to have molecular masses of 44 kDa and to be insensitive to ADP-ribosylation by pertussis toxin. They share 67% amino acid sequence identity with each other and less than 45% identity with other alpha subunits. Their transcripts can be detected in every tissue examined, although the relative levels of the G alpha 13 message appear somewhat variable. PMID- 1905814 TI - Heterologously expressed serotonin 1A receptors couple to muscarinic K+ channels in heart. AB - In cardiac atrial cells, muscarinic acetylcholine receptors activate a K+ current directly via a guanine nucleotide-binding protein (G protein). Serotonin type 1A receptors may activate a similar pathway in hippocampal neurons. To develop a system in which receptor/G protein/K+ channel coupling can be experimentally manipulated, we have used a highly efficient recombinant vaccinia virus vector system to express human serotonin 1A receptors in primary cultures of rat atrial myocytes. The expressed 1A receptors activated the inwardly rectifying K+ conductance that is normally activated by the endogenous muscarinic acetylcholine receptors. Maximal responses to either agonist occluded further activation by the other agonist. The average activation time constants for serotonin were about 5 times slower than for acetylcholine. The data support suggestions that the intracellular signaling pathway from seven-helix receptors to G proteins and directly to ion channels is widespread in excitable cells. After a fraction of the G proteins are activated irreversibly by guanosine 5'-[gamma thio]triphosphate, subsequent transduction proceeds more efficiently. One possible interpretation is that multiple G-protein molecules are required to activate each channel. Vaccinia virus expression vectors are thus useful for expressing seven-helix receptors in primary cultures of postmitotic cells and have provided a heterologous expression system for the signaling pathway from seven-helix receptors to G proteins and directly to ion channels. PMID- 1905813 TI - G alpha 16, a G protein alpha subunit specifically expressed in hematopoietic cells. AB - Signal-transduction pathways mediated by guanine nucleotide-binding regulatory proteins (G proteins) determine many of the responses of hematopoietic cells. A recently identified gene encoding a G protein alpha subunit, G alpha 16, is specifically expressed in human cells of the hematopoietic lineage. The G alpha 16 cDNA encodes a protein with predicted Mr of 43,500, which resembles the G q class of alpha subunits and does not include a pertussis toxin ADP-ribosylation site. In comparison with other G protein alpha subunits, the G alpha 16 predicted protein has distinctive amino acid sequences in the amino terminus, the region A guanine nucleotide-binding domain, and in the carboxyl-terminal third of the protein. Cell lines of myelomonocytic and T-cell phenotype express the G alpha 16 gene, but no expression is detectable in two B-cell lines or in nonhematopoietic cell lines. G alpha 16 gene expression is down-regulated in HL-60 cells induced to differentiate to neutrophils with dimethyl sulfoxide. Antisera generated from synthetic peptides that correspond to two regions of G alpha 16 specifically react with a protein of 42- to 43-kDa in bacterial strains that overexpress G alpha 16 and in HL-60 membranes. This protein is decreased in membranes from dimethyl sulfoxide-differentiated HL-60 cells and is not detectable in COS cell membranes. The restricted expression of this gene suggests that G alpha 16 regulates cell-type-specific signal-transduction pathways, which are not inhibited by pertussis toxin. PMID- 1905815 TI - The type I human T-cell leukemia virus (HTLV-I) Rex trans-activator binds directly to the HTLV-I Rex and the type 1 human immunodeficiency virus Rev RNA response elements. AB - The Rex protein of the type I human T-cell leukemia virus (HTLV-I) is essential for the replication of this pathogenic retrovirus and, surprisingly, can also replace the function of the structurally distinct Rev protein of the type 1 human immunodeficiency virus (HIV-1). Rex action requires a 255-nucleotide viral RNA stem-loop structure termed the Rex RNA response element (RexRE) located in the 3' retroviral long terminal repeat. Rex function leads to the induced cytoplasmic expression of the incompletely spliced family of viral mRNAs that uniquely encode the HTLV-I structural and enzymatic proteins (Gag, Pol, and Env). Our studies now demonstrate that Rex acts by binding directly to the RexRE in a sequence-specific manner. These effects of Rex require the presence of a 10-nucleotide subregion of the RexRE that is essential for Rex function in vivo. Dominant-negative mutants of Rex also bind to the RexRE with high affinity, while a recessive-negative Rex mutant altered within its arginine-rich, positively charged domain fails to engage the RexRE. Analogously, both the wild-type and dominant-negative Rex proteins specifically bind to the structurally distinct HIV-1 Rev response element, a finding that likely underlies the respective stimulatory and inhibitory effects of these HTLV-I proteins in the heterologous HIV-1 system. However, consistent with their lack of amino acid homology, the binding sites for Rex and Rev within the HIV-1 Rev response element are distinct. PMID- 1905816 TI - Zygotic genes that mediate torso receptor tyrosine kinase functions in the Drosophila melanogaster embryo. AB - The developmental signal that specifies the fates of cells at the anterior and posterior termini of the Drosophila embryo is transmitted by the torso receptor tyrosine kinase. This paper presents the results of a genetic interaction test for zygotic loci that act downstream of torso in the terminal genetic hierarchy. Tests of 26 zygotic mutants with defects in terminal development indicate that at least 14 reside in this hierarchy. The phenotypes associated with these genes fall into three classes, each of which represents a distinct aspect of terminal development and evolution. Four of the genes have been molecularly cloned and their products include an intercellular communication factor and three kinds of transcription factors. PMID- 1905817 TI - Measurement of distinct immunochemical presentations of tau protein in Alzheimer disease. AB - The tau protein is a microtubule-associated protein that is normally located in nerve axons. In Alzheimer disease, it is a constituent of paired helical filaments (PHFs), which are the principal fibrous component of the characteristic neurofibrillary tangles. The tau protein, therefore, is abnormally sequestered in an insoluble form in PHFs in the cell body and dendrites in Alzheimer disease. We have used two monoclonal antibodies (mAbs) to selectively measure the levels of normal, soluble tau protein and of PHF-associated tau protein in the brain. mAb 423 binds to PHFs and recognizes a 12-kDa fragment of tau protein released by formic acid treatment of PHFs, but it does not recognize normal tau protein. In contrast, mAb 7.51 recognizes normal tau protein as well as the PHF core-derived tau fragment, but its epitope is concealed in the PHF-bound form. The differential binding properties for these two mAbs have enabled us in this study to quantify insoluble PHF-associated tau protein in the somatodendritic compartment as well as normal soluble tau protein in its predominantly axonal location. Our findings demonstrate that a distinct immunochemical presentation of tau protein recognized by mAb 423, a PHF-specific marker, can be used to quantify neurofibrillary pathology in Alzheimer disease independently of the presence of normal tau proteins. PMID- 1905818 TI - Isolation and characterization of a gene encoding a G-protein alpha subunit from Schizosaccharomyces pombe: involvement in mating and sporulation pathways. AB - The gpal gene of Schizosaccharomyces pombe, which encodes a protein homologous with the alpha subunits of mammalian guanine nucleotide-binding proteins (G proteins), was isolated by cross-hybridization using rat Gi1 alpha and Gx alpha cDNA. The deduced amino acid sequence was about 37% identical with rat Gi1 alpha and Gx alpha proteins and contained three conserved motifs commonly found in all GTP-binding proteins. Disruption of gpa1 was not lethal but conferred sterility and sporulation deficiency on Sch. pombe cells. Thus, the gene is essential for the sexual development and is probably coupled to mating-factor receptors. In contrast to Saccharomyces cerevisiae GPA1, which plays a negative role in mating factor signal transduction, Sch. pombe gpa1+ apparently has a positive function. A gpa1 transcript of 2.2 kilobases was detected in vegetatively growing cells. A 1.6-kilobase gpa1 transcript appeared in addition to the 2.2-kilobase transcript when cells were derepressed for mating or meiosis. PMID- 1905819 TI - Analysis of Kruppel control elements reveals that localized expression results from the interaction of multiple subelements. AB - The Drosophila gap gene Kruppel (Kr) displays a complex spatiotemporal pattern of expression during embryogenesis. Using P-element transformation experiments, we demonstrate that control elements guiding Kr expression in the central or in the anterior domain at the blastoderm stage are each composed of multiple subelements that interact synergistically. We provide evidence that bicoid (bcd) and hunch back (hb) gene products, as well as at least one other activator, are needed to activate Kr expression in the central domain. We localize and describe regulatory elements within the 4.1-kilobase region proximal to the Kr promoter that are responsible for expression in the ectoderm, mesoderm, amnioserosa, and nervous system. Finally, a protein instability motif encoded in the second exon appears to be important for resetting the dynamic Kr pattern. PMID- 1905821 TI - Chemiexcitation in the arachidonic acid cascade. AB - As investigated in neutrophils, the very weak luminescence accompanying the arachidonic acid cascade is associated with the lipoxygenase pathway. The emission is dramatically enhanced by energy transfer to chlorophyll a. The number of chlorophyll molecules excited to the fluorescent state per oxygen consumed, (the S1/O2 ratio), equal to the product of the quantum yields of chemiexcitation and of energy transfer, is 5.4 x 10(-6). The quantum yield of chemiexcitation is inferred to be higher than 1 x 10(-3). The two most likely chemiexcitation routes point to triplet conjugated carbonyls as the most likely candidates for the excited species that transfer to chlorophyll. As such the emission intensity may reflect the level of hydroperoxyeicosatetraenoic acid. This is the first case where addition of a biotic substrate to a cellular system results in substantial generation of electronic excited states without any drastic loss of cell viability. Whether the formation of excited states in the arachidonic acid cascade in neutrophils is accidental or has a biological role is an open question. PMID- 1905820 TI - Positive inotropic action of veratridine in rat atria: possible involvement of prostanoids. AB - Veratridine caused a positive inotropic action in the electrically driven left atria of rats. Quinacrine (a phospholipase A2 inhibitor), indomethacin (a cyclooxygenase inhibitor) and aspirin (a cyclooxygenase inhibitor), but not nordihydroguaiaretic acid (a lipoxygenase inhibitor), inhibited the response to veratridine. Verapamil and nifedipine also inhibited the response to veratridine. The positive inotropic effect of arachidonic acid was abolished by aspirin and indomethacin. However, the positive inotropic effect of PGF2 alpha was not affected by indomethacin, quinacrine or aspirin. PGE2, but not STA2 and PGI2, also caused the positive inotropic effect. However, the negative inotropic effect was observed in the presence of PGE1 and PGD2. Veratridine shifted the concentration-response curve of Ca2+ to the left in a Ca(2+)-free medium. Indomethacin only inhibited the veratridine-induced potentiation of Ca2+ responses. Veratridine increased the level of PGF2 alpha in the left atria and this action was completely inhibited by indomethacin, aspirin and quinacrine. Veratridine also increased the level of PGE2. These results imply that the positive inotropic action of veratridine is partly due to stimulation of the release of arachidonic acid leading to the increase in prostaglandins in rat atria. PMID- 1905822 TI - Intraventricular insulin reduces food intake and body weight of marmots during the summer feeding period. AB - The study presented below describes experiments that investigate the ability of insulin to inhibit food intake in awake, active marmots during the summer season. Our results suggest that increasing intraventricular insulin concentration during the summer active feeding period will cause a decrease in food intake and body weight of marmots. When infused with insulin into their lateral ventricles (Alzet #2002 minipumps), animals had significantly lower food intake as compared to their food intake during the control period. In addition, these animals lost body weight during the period of the insulin infusion. We suggest that during the summer when marmots are not hibernating and are actively feeding, brain insulin levels may play a role in regulating food intake. PMID- 1905823 TI - Reduced mortality of manic-depressive patients in long-term lithium treatment: an international collaborative study by IGSLI. PMID- 1905824 TI - Common sense, documentation, and the method of unrestricted exegesis: their value and limitations examined in four letters by Freud. PMID- 1905825 TI - Bringing the Holocaust home: the Freudian dynamics of Kubrick's The Shining. PMID- 1905826 TI - Listening: a communication. PMID- 1905827 TI - Gender specific dangers in the female dyad in treatment. PMID- 1905828 TI - A comparative study of Japanese and American group dynamics. PMID- 1905829 TI - Psychosis and malice. PMID- 1905830 TI - Freud and tragic affect: the pleasures of dramatic pain. PMID- 1905831 TI - [Protein-calorie malnutrition in people from Third-World countries and from here]. PMID- 1905832 TI - [Parkinson's disease and epilepsy]. AB - We report the case of a woman suffering from complex partial seizures who developed Parkinson's disease at the age of 58. Parkinsonian symptoms improved transitorily after complex partial seizures. Although this has been reported after generalized seizures, this case is, to our knowledge, the first description of improvement of parkinsonian symptoms following a complex partial seizure. PMID- 1905833 TI - [Contribution of pure FSH in ovulation induction excluding fertilization in vitro]. AB - The use of pure FSH reduces the likelihood of multifollicular development and increases the safety of ovulation induction without affecting the overall pregnancy rate. The authors propose a "slow" protocol, which is said to provide the same level of safety, but also to increase the number of pregnancies. PMID- 1905834 TI - [The use of LHRH analogs in ovulation induction]. AB - The use of LH-RH agonists is appropriate for the stimulation of ovulation. In contrast, in the case of induction of ovulation in a patient with deficient ovulation, suppression of influences of the hypothalamo-pituitary axis does not modify the pathological condition responsible for the ovulatory anomaly. PMID- 1905835 TI - [Post-hepatitis B, B-D and C cirrhosis]. AB - Three viruses are responsible for posthepatitic cirrhosis: hepatitis B virus, hepatitis D (also called delta) virus and hepatitis C virus formerly known as non A, non-B virus. Delta virus is a defective organism which can replicate only when coinfection with hepatitis B virus is present. These three viruses cause chronic active hepatitis which, after a period of 5 to 30 years, gives rise to posthepatitic cirrhosis. Chronic infections with these viruses account for more than 90 p. 100 of chronic active hepatitis in France and constitute a major cause of cirrhosis. Beside complications (hepatocellular insufficiency, portal hypertension, hepatocellular carcinoma) which are common to all types of cirrhosis irrespective of their origin, the course of posthepatitic cirrhosis is characterized by possible episodes of reactivation of chronic hepatitis and by a very high risk of hepatocellular carcinoma. Two kinds of treatment are now available: antiviral therapy (basically with interferon alpha) and liver transplantation. Antiviral therapy must, of course, be given before the stage of cirrhosis has been reached. Liver transplantation in these patients raises special problems due to recurrence of viral infection in the graft. Vaccination against hepatitis B virus, which also prevents the B-delta coinfection, must be systematic in populations at risk. PMID- 1905836 TI - Gamma globulin prophylaxis to reduce post-transfusion non-A, non-B hepatitis after cardiac surgery with cardiopulmonary bypass. AB - A prospective, randomized study of immune serum globulin (ISG) for prevention of post-transfusion hepatitis was performed on 196 patients (100 controls without gammaglobulin or placebo and 96 who received ISG) undergoing valve replacement or coronary artery bypass with extracorporeal circulation. The dose of ISG was 2 ml i.m. at premedication and 2 ml i.m. on postoperative day 3. Probable non-A, non-B hepatitis developed postoperatively in ten of the 100 controls and two of the 96 in the ISG group. Two ISG patients and three controls with non-A, non-B hepatitis still have increased serum aminotransferase values after 3-5 years, but liver biopsy revealed hepatitis, which histologically was very mild, in only two control and two ISG patients. Low-dose gamma globulin thus reduced the incidence of acute, probable non-A, non-B hepatitis in cardiac surgery with cardiopulmonary bypass. PMID- 1905837 TI - [An anthrax epidemic in Switzerland. Clinical, diagnostic and epidemiological aspects of a mostly forgotten disease]. AB - On average in Switzerland there is only one case of human anthrax every two years, and this is almost exclusively caused through contact with sick animals in agriculture. However, within less than 3 years, 25 workers in one textile factory have contracted this anthropo-zoonosis. 24 cases had cutaneous and one inhalation anthrax. The infection was imported in goat's hair from Pakistan. This almost unique industrial epidemic was due to various circumstances. In particular, the rarity of the illness contributed to a general lack of experience and therefore hindered recognition of the clinical symptoms. In addition, repeated attempts failed to identify the pathogenic agent conclusively. In most cases, the diagnosis was only confirmed retrospectively using the Russian allergen "Anthraxin"--an intracutaneous test unknown up to that time in human medicine in the West--and later also by EIA. All the patients recovered. The clinical picture, diagnosis and epidemiology of cutaneous anthrax are described in detail. The typical features are, in the beginning, a pruritic insect-bite-like pimple, then a painless ulcer surrounded by serous-hemorrhagic, often rapidly confluent vesicles and non-pitting edema. On the ground of the ulcer a black necrosis develops which is never colliquative but is transformed into the typical pitch black firmly adherent eschar. Lymphadenitis and lymphangitis are concomitant manifestations. The bacteriological findings and occupational history are decisive for the diagnosis. Anthrax spores can survive many decades. The vegetative organisms are highly susceptible to almost all antibiotics. The latter prevent the invasion of the anthrax bacilli and the toxinemia if administered in time, but they do not influence the development of the local lesions. For the detection of anthrax bacillus, sterile swabs should be soaked in the fluid of the vesicles. It must be done before beginning of any antibiotic treatment. For the examination of animal products, preparatory procedures are necessary to destroy contaminants that may be antagonistic to or overgrow Bacillus anthracis. PMID- 1905838 TI - [Inhalation anthrax in a textile worker: non-fatal course]. AB - The development of dyspnea, hematemesis, melaena and symptoms of shock following an apparently minor infection of the upper respiratory tract in a 37-year-old textile worker marked the onset of an acute threatening illness. Pleuracentesis revealed 3.8 l of hemorrhagic exudate. Chest x-rays showed a significant increase in mediastinal width. Conspicuous laboratory findings were hemoconcentration, anemia and leukocytosis, and increased serum activities for SGOT, SGPT and alkaline phosphatase. The infection occurred during an industrial epidemic of 24 cases of cutaneous anthrax, and the diagnosis of inhalation anthrax was based on the occupational exposure and a positive "Anthraxin" skin test which was later confirmed by EIA. The patient survived the usually fatal illness after treatment with antibiotics and prednisolone. PMID- 1905839 TI - Residues of chlorinated biphenyl congeners and pesticides in brain and liver of the oystercatcher (Haematopus ostralegis) in relation to age, sex and biotransformation capacity. AB - Polychlorinated biphenyl concentrations in brain and liver oystercatchers, Haematopus ostralegis, increased similarly in males and females until sexual maturation. The concentrations were higher in adult males than in subadults, but for females the concentrations were lower in adults than in subadults. Absolute PCB, dieldrin and DDE concentrations were higher in liver than in brain. Compared with these compounds, alpha-HCH was relatively enriched in brain. No significant relation between pesticide concentrations and age or sex could be established. Despite differences in absolute PCB concentrations, the PCB patterns were very similar between all categories of birds and between brain and liver of the same animals. Only in the brain of juvenile males were some congeners present in relatively higher concentrations than in the brain of subadults and adults. Oystercatchers are able to metabolize CB congeners with vicinal H-atoms in the meta and para positions irrespective of the number of ortho-chlorines present. However, their ability to metabolize congeners with vicinal H-atoms in the ortho and meta positions is limited. PMID- 1905840 TI - p53 mutations in human cancers. AB - Mutations in the evolutionarily conserved codons of the p53 tumor suppressor gene are common in diverse types of human cancer. The p53 mutational spectrum differs among cancers of the colon, lung, esophagus, breast, liver, brain, reticuloendothelial tissues, and hemopoietic tissues. Analysis of these mutations can provide clues to the etiology of these diverse tumors and to the function of specific regions of p53. Transitions predominate in colon, brain, and lymphoid malignancies, whereas G:C to T:A transversions are the most frequent substitutions observed in cancers of the lung and liver. Mutations at A:T base pairs are seen more frequently in esophageal carcinomas than in other solid tumors. Most transitions in colorectal carcinomas, brain tumors, leukemias, and lymphomas are at CpG dinucleotide mutational hot spots. G to T transversions in lung, breast, and esophageal carcinomas are dispersed among numerous codons. In liver tumors in persons from geographic areas in which both aflatoxin B1 and hepatitis B virus are cancer risk factors, most mutations are at one nucleotide pair of codon 249. These differences may reflect the etiological contributions of both exogenous and endogenous factors to human carcinogenesis. PMID- 1905841 TI - Top predators in the Southern ocean: a major leak in the biological carbon pump. AB - Primary productivity in the Southern Ocean is approximately 3.5 gigatons of carbon per year, which accounts for nearly 15 percent of the global total. The presence of high concentrations of nitrate in Antarctic waters suggests that it might be possible to increase primary production significantly and thereby alleviate the net accumulation of atmospheric carbon dioxide. An analysis of the food web for these waters implies that the Southern Ocean may be remarkably inefficient as a carbon sink. This inefficiency is caused by the large flux of carbon respired to the atmosphere by air-breathing birds and mammals, dominant predators in the unusually simple food web of Antarctic waters. These top predators may transfer into the atmosphere as much as 20 to 25 percent of photosynthetically fixed carbon. PMID- 1905842 TI - Identification of the envelope V3 loop as the primary determinant of cell tropism in HIV-1. AB - Cells of the monocyte-macrophage lineage are targets for human immunodeficiency virus-1 (HIV-1) infection in vivo. However, many laboratory strains of HIV-1 that efficiently infect transformed T cell lines replicate poorly in macrophages. A 20 amino acid sequence from the macrophage-tropic BaL isolate of HIV-1 was sufficient to confer macrophage tropism on HTLV-IIIB, a T cell line--tropic isolate. This small sequence element is in the V3 loop, the envelope domain that is the principal neutralizing determinant of HIV-1. Thus, the V3 loop not only serves as a target of the host immune response but is also pivotal in determining HIV-1 tissue tropism. PMID- 1905843 TI - Central venous catheters. Technique and experience at Red Cross War Memorial Children's Hospital, Cape Town, 1987-1990. AB - Central venous catheters can be of major benefit to children in whom prolonged intravenous access is required. For their everyday use, however, the known associated morbidity needs to be at an acceptably low level. Experience with 44 central venous catheters in 31 children (3318 catheter days over a 40-month period) is reported. The complication rate of catheter sepsis (0.3/100 catheter days), thrombosis (1 catheter), and technical problems (17, of which 6 required removal) justified catheter usage. Provided catheters are correctly inserted and the patients meticulously nursed, these catheters offer major advantages to infants and children requiring long-term intravenous access, particularly for parenteral nutrition. PMID- 1905844 TI - [Pseudo-allergy]. PMID- 1905845 TI - [Role of respiratory regulation in the formation of respiratory insufficiency in patients with chronic bronchitis]. PMID- 1905846 TI - Fibrin-dependent fibrinolytic activity during extracorporeal circulation. AB - Cardiopulmonary By-Pass (CPB) Surgery may at times induce a haemostatic defect, at present not too well understood, causing severe bleeding from the operative site and chest tube drain. We present here some data on antigen increase in tissue Plasminogen Activator (tPA) and D 2 Dimer (D2D) detected during CPB and apparently not compensated by enhanced Plasminogen Activator Inhibitor type 1 (PAI 1) activity. tPA concentration (antigenic) ranged around 6.15 ng/ml (SD 5.6) before thoracotomy and 5.8 g/ml (SD 4.74) 5-10 minutes after a heparin 250 IU/Kg bolus injection. During CPB, tPA increased to 20.34 ng/ml (SD 9.17) before protamine infusion, and 16.93 ng/ml (SD 8.13) after heparin neutralization. As the D2D went up to 2000-4000 ng/ml (before/after protamine) and it was not correlated by fibrinogen consumption or FDP production, we find these observations suggestive of fibrin-dependent fibrinolytic activity, as an acquired haemostatic defect developed during CPB. PMID- 1905847 TI - Thrombin decreases glycosaminoglycans content of endothelial cells in culture. AB - The effect of thrombin on the metabolism of glycosaminoglycans (GAG) in cultured bovine aortic endothelial cells was investigated. Incubation of confluent endothelial cell cultures with thrombin at 1.0 NIH U/ml for 8 h and above caused a significant decrease in the accumulation of [35S]sulfate-labeled GAG (35S-GAG) in the cell layer. After a 24 h incubation, thrombin at 0.5 U/ml and above decreased the accumulation of 35S-GAG in both cell layer and medium. The percentage of 35S-GAG released into the medium during the last 3 h of 24 h incubation was significantly increased by thrombin. In thrombin-treated cell layer, both heparan sulfate and the other GAG was significantly decreased at the same degree. The incorporation of both [3H]thymidine and [14C]leucine was significantly increased by thrombin. Gabexate mesilate, a serine protease inhibitor, suppressed the thrombin inhibition. From these results, it was suggested that thrombin decreased 35S-GAG in the endothelial cell layer without a nonspecific damage of the cells through mainly an inhibition of GAG production and additionally a stimulation of GAG release. PMID- 1905848 TI - Reproducibility of one-stage, two-stage and chromogenic assays of factor VIII activity: a multi-center study. AB - This study was aimed at assessing the reproducibility of Factor VIII assays between different laboratories using the same reagents. A total of 176 post-dose plasma samples were obtained from 8 Italian subjects with hemophilia-A treated with a single dose of Factor VIII concentrates. Three laboratories (in FRG, Italy, and Sweden) participated in the study. Frozen aliquots of each sample were dispatched to each of the laboratories, where the aliquots were assayed using the same one-stage, two-stage and chromogenic methods. The one-stage and the chromogenic methods were well reproducible between the three centers: pairwise correlation analyses yielded r-values ranging from 0.88 to 0.91 for the one-stage method and from 0.91 to 0.96 for the chromogenic method. The agreement between these two assays was less evident in samples with activity below 200 IU/L in which the one-stage gave, on average, higher Factor VIII concentrations than those provided by the chromogenic method. The two-stage method was not well reproducible, and the pairwise r-values ranged from 0.48 to 0.73. Our study emphasises the need to develop multi-center quality control programs to verify the reproducibility of Factor VIII assays. PMID- 1905849 TI - The platelet-reactivity-test--a useful "by-product" of the blood-sampling procedure? AB - Blood sampling demands the insertion of a needle into the blood-vessel thereby causing a destruction of the endothelial wall of the blood-vessel. The physiological reaction of platelets is the occlusion of endothelial lesions. Reaction of platelets induced by endothelial lesions lasts about 10 ms. Each blood sampling procedure should therefore activate platelets. A simple platelet test-system was designed following these considerations. Blood samples were collected twice, in EDTA-buffer and in EDTA-formalin-buffer. Activated (aggregated) platelets were fixed by formalin or dissolved in EDTA-buffer. Platelet-reactivity (PR) was calculated as quotient of the number of platelets remaining in the supernatant of both samples after centrifugation. The PR-index values strongly depended on the blood-sampling procedure. Standardization of the blood sampling procedure led to normal distributed PR-index-values in 110 healthy controls (0.98 +/- 0.09). PR-index-values remained constant during a period of 260 days. PR-index-values in 49 patients suffering from encephalomyelitis disseminata were 1.04 +/- 0.15 and 1.64 +/- 0.6 in 72 patients suffering from transitoric ischemic attacks. Differences between healthy controls and patients suffering from TIA's were significant (p less than 0.001). PMID- 1905850 TI - Fibrinogen does not protect von Willebrand factor against proteolysis by human cathepsin G. AB - The susceptibility of von Willebrand factor /vWF/ to digestion by human neutrophil cathepsin G in highly purified FVIII/vWF concentrate /BHS/ and in cryoprecipitate has been studied. In contrast to human neutrophil elastase, cathepsin G inactivates and degrades vWF not only in BHS but also in cryoprecipitate. Fibrinogen added in excess to purified FVIII/vWF concentrate does not protect vWF against cathepsin G proteolysis. Biological significance of this phenomena are discussed. PMID- 1905851 TI - The stimulatory effect of soluble fibrin on plasminogen activation by tissue plasminogen activator as studied by the Coa-set Fibrin Monomer test. AB - The stimulatory effect of various fibrin preparations on plasminogen activation by tissue plasminogen activator, was studied by the Coa-set Fibrin Monomer test (Kabi). Fibrin obtained by complete conversion of purified fibrinogen demonstrated a greater stimulatory effect on plasminogen activation than did equal amounts of fibrin obtained by partial conversion of fibrinogen. Soluble fibrin generated by treating human plasma with minute amounts of thrombin or bathroxobin, resembled partially converted purified fibrinogen. The plasminogen activating effect of completely converted fibrinogen was similar in thrombin and bathroxobin incubated samples. In preparations of partially converted fibrinogen and in plasma samples, bathroxobin digested fibrinogen expressed a more pronounced stimulatory effect on plasminogen activation than did thrombin digested specimens. The underlying mechanism for these differences are discussed. PMID- 1905852 TI - [Ambulatory coronary angiography. Organization--patient safety--economic benefits]. AB - 916 (63%) of 1,452 coronary angiographies performed at the University Hospital in Trondheim from 1988 to 1990 were done policlinically. The study shows that coronary angiography can be carried out safely on an outpatient basis, and that more than 50% of all patients admitted for a coronary angiography can be examined in this way. PMID- 1905853 TI - Hepatic energy metabolism during hypothermic storage and after reperfusion. Evaluation of the University of Wisconsin and the Bretschneider solutions. PMID- 1905854 TI - [Multiple recurrences of meningococcal infection]. PMID- 1905855 TI - [Sleep and epilepsy]. AB - The frequency of epileptiform discharges shows a wide intraindividual variability; it is influenced by the sleep-waking cycle and by the different stages of sleep: generalized seizures (tonic-clonic, tonic and myoclonic) are activated in nonrapid eye movement sleep, partial seizures tend to have more complex relationships with sleep states. Generally, sleep stages I and II and transit stages have an activating effect on discharges. Rapid eye movement sleep has an "anticonvulsive" effect and focalizes paroxysmal activity. Sleep recordings are useful for localizing a focus in temporal lobe seizures and for differentiation of epileptic seizures from non-epileptic seizure-like sleep disturbances. EEG after sleep deprivation should be used in patients suspected of suffering from epilepsy whose prior EEGs (including hyperventilation, photic stimulation and short sleep) were normal or yielded borderline abnormalities. Epileptiform discharges can--without clinical seizures--produce arousal reactions and sleep disturbances. PMID- 1905857 TI - [Possible complications of drug-induced asthma therapy]. PMID- 1905856 TI - [Thrombolysis in acute occlusion of cerebral blood vessels]. AB - Thrombolysis may achieve recanalization in cases of occlusion of the cerebral vessels. If therapy is initiated in good time, development of cerebral infarction may be at least partially prevented. Thrombolytic treatment was performed in 14 patients at the Wagner-Jauregg Hospital within a period of one year. Urokinase was given locally, while rtPA was applied locally and/or systemically. 4 patients had an occlusion of the internal carotid artery, 6 an occlusion of the middle cerebral artery, and 4 an occlusion of the basilar artery. Complete recanalization was achieved in 6 patients, partial recanalization in 4, and no recanalization in 4. The neurological outcome of the cases with complete recanalization was good with the exception of one patients who died. Partial recanalization resulted in a fair outcome in 2 patients, while the other 2 died. 3 out of the 4 patients in whom no recanalization was achieved died. Our findings show that this form of therapy may considerably improve the natural history of the disease, provided recanalization is achieved in good time. They encourage us to continue this form of therapy and to work at improving the therapeutic criteria. PMID- 1905858 TI - Influence of the codon following the initiation codon on the expression of the lacZ gene in Saccharomyces cerevisiae. AB - A set of 32 different codons were introduced in a lacZ expression vector (pPTK400) immediately 3' from the AUG initiation codon. Expression of the lacZ gene was determined in Saccharomyces cerevisiae by measuring the amount of beta galactosidase fusion protein using immuno-gel electrophoresis. A 5.3-fold difference in expression was found among the various constructs. It was found that there was no preference for a certain nucleotide in any position of the second codon and there was no distinct correlation between the level of tRNA corresponding to any particular second codon and expression. No correlation could be found between the local secondary structure and expression. When the overall codon usage in yeast and the codon usage in the second position of the mRNA is compared, there is no obvious significant difference in preference. This indicates that in yeast, in contrast to Escherichia coli, the codon choice at the beginning of the mRNA does not deviate from the one further downstream and is determined by the requirements for optimal translation elongation. Important determinants of the optimal context for an initiation codon in yeast therefore must be located mainly 5' from this codon. PMID- 1905859 TI - Quantitation of readthrough of termination codons in yeast using a novel gene fusion assay. AB - A simple quantitative in vivo assay has been developed for measuring the efficiency of translation of one or other of the three termination codons. UAA, UAG and UGA in Saccharomyces cerevisiae. The assay employs a 3-phosphoglycerate kinase-beta-galactosidase gene fusion, carried on a multicopy plasmid, in which the otherwise retained reading frame is disrupted by one or other of the three termination codons. Termination readthrough is thus quantitated by measuring beta galactosidase in transformed strains. Using these plasmids to quantitate the endogenous levels of termination readthrough we show that readthrough of all three codons can be detected in a non-suppressor (sup+) strain of S. cerevisiae. The efficiency of this endogenous readthrough is much higher in a [psi+] strain than in a [psi-] strain with the UGA codon being the leakiest in the nucleotide context used. The utility of the assay plasmids for studying genetic modifiers of nonsense suppressors is also shown by their use to demonstrate that the cytoplasmic genetic determinant [psi+] broadens the decoding properties of a serine-inserting UAA suppressor tRNA (SUQ5) to allow it to translate the other two termination codons in the order of efficiency UAA greater than UAG greater than UGA. PMID- 1905860 TI - [Feeding activity, spontaneous activity and body core temperature of saddle-back tamarins (Saguinus fuscicollis)]. AB - Eating behaviour and spontaneous activity (videometry) as well as deep body temperature (radiotelemetry) of 3 adult Saddle Back Tamarins (Saguinus fuscicollis) were investigated (singly housed, environmental temperature 28 degrees C, relative air humidity 60%, light 6:00-18:00 h, drinking-water and pelleted colony diet ad lib.). The experimental animals (1 female, 2 males; 3-8 years old), born in captivity, showed only some slight individual differences within their inborn species pattern, with regard to the 3 measured parameters. The monkeys were, like wild-living individuals, strictly light-active. They moved in the day-time nearly uninterrupted without special rhythm and slept remarkably deep through the whole night. Food intake occurred during the whole day with varying intensity. The body temperature of the 3 monkeys showed individual daytime-means between 38.8-39.9 degrees C, whereby the temperature fluctuated dependent on their moving activity with a range of about +/- 0.5 degrees C. At night the body temperature of the animals averaged between 35.9-36.6 degrees C. PMID- 1905861 TI - Changes in feeding behavior and plasma vasopressin concentration during water deprivation in goats. AB - To further characterize the suppression of feeding that normally accompanies water deprivation and to test whether vasopressin contributes to this hypophagia, food intake, meal patterns and plasma vasopressin concentrations were measured during 24 h or 72 h of water deprivation in pygmy goats. The effects of exogenous vasopressin and of a V1-receptor antagonist on feeding during water deprivation were also assessed. The hypophagia during water deprivation was primarily due to decreases in meal size. The plasma vasopressin concentration increased about 2.5 fold and 10-fold after 24 and 72 h of water deprivation, respectively. Plasma osmolality also increased (measured only after 72 h of water deprivation). Intraperitoneally (ip) injected vasopressin (1.5 micrograms/kg b. wt.) that previously reduced food intake in goats with ad lib, access to water (Meyer et al., 1989), failed to affect cumulative food intake in water deprived goats, but led to a transient increase in meal size. The V1-receptor antagonist (2.5 micrograms/kg b. wt., ip) did not affect cumulative food intake or meal patterns either. These findings indicate that endogenous vasopressin is not crucially involved in the hypophagia during water deprivation. The results are in line with the hypothesis that an abnormal prandial increase in the osmolality of the ruminal fluid is a major contributor to the hypophagia during water deprivation. PMID- 1905862 TI - Influence of various adjuvants on the synthesis of specific antibodies of chicken, sheep and rabbit following immunization with an hapten. AB - In order to obtain high amounts of specific antibodies against the hapten methylphosphoric acid, para-aminophenyl-1,2,2-trimethyl-propyldiester (MATP) different animals were immunized with MATP coupled to the carrier protein human serum albumin (MATP12-HSA) using several adjuvants. The best specific immune response in sheep, rabbit and chicken was reached with Freund's complete adjuvant with animal specific differences being tested by an ELISA. The adjuvants aluminium hydroxide (5% and 10%) and diphosphoryl lipid A showed no significant difference compared to the control group (NaCl with MATP12-HSA). In rabbits and chickens MATP12-HSA can be used to reach an immune response without the help of an adjuvant. PMID- 1905863 TI - Effect of perinatal anti-TCR2 treatment and thymectomy on serum immunoglobulin levels in the chicken. AB - Treatment of chickens as embryos and in the first six days after hatching with mg amounts of anti-TCR2 (alpha beta T cell antigen receptor) antibody plus thymectomy 6 to 8 days after hatching suppressed by more than 90% the TCR2 and TCR1 (TCR gamma delta) subpopulations in the blood. Thymectomy alone resulted only in a profound reduction (greater than 90%) of the absolute number of TCR1 cells, while the absolute number of TCR2 cells was reduced only by 65%. We were interested in the regulation of the immunoglobulin synthesis in these T cell deficient chickens. We determined serum IgG, IgM and IgA levels and found a profound selective reduction (by about 90% on average) of the serum IgA level in anti-TCR2 antibody treated plus thymectomized chickens. In chickens which had been thymectomized only, the serum IgA level was reduced on average only by about 60%. Serum IgG and IgM levels were not reduced in any group. Thus, there was a positive correlation of the serum IgA level and the absolute number of TCR2 cells in all groups. These results indicate that T cells which play a role in IgA specific isotype switching or in IgA B cell differentiation belong to the TCR2 subpopulation. PMID- 1905864 TI - Vitamin A (retinol and retinyl esters), alpha-tocopherol and lipid levels in plasma of captive wild mammals and birds. AB - Vitamin A (retinol and retinyl esters), vitamin E and lipids were determined in a wide variety of wild mammals and birds held in captivity. In mammals plasma levels of vitamin A were generally below 500 ng/ml and those of vitamin E were highly variable (0.1-2 micrograms/ml). In primates, vitamin E levels were 3 to 8 micrograms/ml. Whereas in Marsupialia, Chiroptera, primates, Rodentia, Proboscidea, Sirenia, Perissodactyla and Artiodactyla only retinol was found, retinyl esters (basically retinol palmitate/oleate) represented 10 to 50% of the total plasma vitamin A in some birds of the order Ciconiiformes and Falconiformes. Retinol levels in birds were higher compared to mammals (500-2,000 ng/ml). The same was true for lipids as well as for vitamin E levels (1-26 micrograms/ml) in the plasma of birds. PMID- 1905865 TI - The influence of thiourea on the development of the cultured quail embryo. AB - Although thyroid hormones are known to promote embryonic development, it is still questionable whether the hormones of the thyroid gland exert a stimulatory effect on the early embryo. In attempting to elucidate the thyroid function in this period, we tried to block the synthesis of thyroid hormones by thiourea and followed the embryogenesis under these conditions. The experiments were performed with cultured quail embryos (Coturnix coturnix japonica), which seemed especially suitable for those studies. The results demonstrate that thiourea causes a decrease of the survival rate, DNA-synthesis and of the excretion of uric acid into the allantoic liquid. Furthermore, it exerts an inhibitory effect on weight gain and developmental stages. On the basis of these results it seems very likely, that thyroid hormones exert a stimulatory effect on the development of quail embryos earlier than assumed previously. PMID- 1905866 TI - Concentrations and patterns of released pterins of various animal cell cultures. AB - Neopterin, biopterin, pterin, 6-hydroxymethylpterin and isoxanthopterin were determined in the supernatants of various animal cell cultures. The different cell lines showed distinct variations in the concentrations as well as in the pattern and total amount of the released pterins. In cells from the same organ but from diverse species differences in pattern and release were found. Cell lines derived from primates had a high release of neopterin. A further difference resulted from the origin of fetal or adult organs. Neoplastic cell lines showed different patterns of pterins, dependent on the type of tumour. Primary cultures from embryonic bovine lung had the highest total amount of released pterins in all cell lines examined. PMID- 1905867 TI - Osteopenia caused by ovariectomy in young female rats and prophylactic effects of 1,25-dihydroxyvitamin D3. AB - Young female rats were subjected to either bilateral ovariectomy or sham operation. One group of ovariectomized (ovx) animals was treated with the vitamin D metabolite 1,25(OH)2D3 after surgery. The effects of ovariectomy and 1,25(OH)2D3 treatment on different markers of bone formation (serum alkaline phosphatase, serum bone gla protein) and bone resorption (fasting urinary hydroxyproline) were determined. All rats were euthanized at 7 weeks post ovariectomy and their first lumbar vertebra were processed undecalcified for quantitative bone histomorphometry. A significant decrease in cancellous bone mass was noted in ovx compared with sham-operated rats. This bone loss was associated with increased biochemical markers of bone formation and bone resorption. Furthermore, ovariectomy led to elevated osteoblast perimeter and osteoid parameters as well as an increased osteoclast number. These data indicate that young growing rats develop osteopenia 7 weeks after ovariectomy which goes along with an accelerated bone turnover. Bone gla-protein, alkaline phosphatase and hydroxyproline can be useful markers in studies with ovx rats. Treatment with 1,25(OH)2D3 led to a lowered urinary hydroxyproline excretion and a significant decrease of osteoclast number whereas histomorphometrical indices of bone formation were nearly unchanged. Cancellous bone mass increased significantly in ovx rats treated with 1,25(OH)2D3 compared with non-treated rats. These results suggest that 1,25(OH)2D3 has a prophylactic effect with regard to bone loss in ovx rats which refers to a diminished bone resorption in the high bone turnover condition of ovx animals. PMID- 1905868 TI - [Genetic fingerprinting of inbred lines, outbred lines, transgenic individuals and 3T3 cells of Mus musculus with the probe B.E.S.T. MZ 1.3]. AB - DNA samples from different inbred strains and F1-hybrids, from two outbred strains and from transgenic animals of the species Mus musculus were tested according to the "DNA fingerprint" technique (Jeffreys et al., 1985) using the B.E.S.T.-probe MZ 1.3 (Fa. Biotest, Frankfurt) and the restriction endonuclease Hinf I. In addition, the same method was applied to two cell types i.e. BALB/3T3 clone A 31 and 3T3 B-SV40. The DNA fingerprinting technique with probe MZ 1.3 proved to be a reliable method for genetic monitoring of different strains of mice. All inbred strains tested as well as their substrains could be identified and distinguished from each other without any doubt. Congenic and transgenic individuals, however, were identical with their background strains. After several in vitro passages, cells from cultures showed the similar DNA configuration as the donor strains. Within outbred strains, it was possible to quantify heterozygosity by the configuration of the DNA-patterns. These results suggest that it might be appropriate to replace the mathematically estimated inbreeding coefficient by so-called identity-coefficient (IK), which would depend on the probe and the restriction endonuclease used (e.g. IKMZ 1.3/Hinf I). Using the MZ 1.3 probe, the DNA fingerprint technique allows a unique genetic identification of different strains of mice and offers, furthermore, the possibility to use a colour kit rather than the usual P-32 marker. PMID- 1905869 TI - Comparative evaluation of specific vaccines and immuno-modulators in disease control of beef cattle. AB - Two field trials were undertaken to evaluate specific vaccines and Biological Response Modifiers (B.R.M.) with regard to disease control of beef cattle. Clinical data and laboratory results strongly suggested a genetically determined resistance to transportation stress of some cattle breeds, with possible important consequences on the occurrence of multi-factor diseases. Plenty of calves showed detectable levels of serum interferon and a remarkable activation of at least some lymphocyte populations in the first days after arrival. In general, B.R.M.-treated cattle could better react against environmental pathogens, as evidenced by both clinical and laboratory findings. Several data emerged that even the efficacy of specific vaccines could be largely accounted for by a positive modulation of non-specific immunity; this latter feature can be mainly referred to adjuvants and/or some bacterial antigens. PMID- 1905870 TI - Adaptation to vestibular disturbances: some clinical implications. AB - A knowledge of the mechanisms used in adaptation to vestibular lesions is important for both diagnostic and therapeutic purposes. Here we discuss commonly encountered circumstances--habitual wearing of spectacles, unilateral or bilateral labyrinthine dysfunction--that call for adaptation. The context specificity of vestibular adaptation is emphasized because of its crucial role in designing programs of physical therapy. The pharmacological manipulation of plasticity, either purposeful facilitation, or inadvertent retardation, is an area of current investigation of direct clinical importance. Finally, the wide range of adaptive responses and strategies available to participate in the compensatory process is emphasized, so that they can be marshalled together to optimize vision and balance. PMID- 1905871 TI - Decisions after first seizure. AB - The probability of an intracerebral neoplasm occurring in patients presenting with first seizure was calculated using the data provided by four recent studies. After recording the history of the patients and performing clinical neurological examinations, the probability of a neoplasm was increased or reduced substantially, allowing rational decision to be made for further investigation or follow-up. The impact of conventional EEG on the probabilities was weak. Decision analysis can be used to improve diagnostic practices. PMID- 1905872 TI - Thrombolysis with recombinant tissue plasminogen activator in acute ischemic stroke: evaluation with rCBF-SPECT. AB - We treated five patients with hemispheric ischemic stroke with intravenous recombinant tissue plasminogen activator (rtPA), within 3-6 h after stroke onset. Regional cerebral blood flow was evaluated with single photon emission computed tomography (rCBF-SPECT) before and after treatment. One patient with aphasia and a moderately severe hemiparesis, who had a small flow deficit, was treated 5 h and 30 min after the onset of his stroke and had a prompt and complete recovery. The post treatment rCBF-SPECT showed normal flow. One patient with a very large flow deficit died of transtentorial herniation. In three other patient clinical condition remained unchanged, in one of them despite restoration of flow, demonstrated by transcranial doppler examination. In all these patients the rCBF SPECT remained abnormal. rCBF-SPECT is a valuable tool in the explanatory analysis of fibrinolytic treatment in ischemic stroke. PMID- 1905873 TI - Intracoronary recombinant tissue-type plasminogen activator in unstable angina: a pilot angiographic study. AB - The effectiveness of intracoronary (IC) recombinant thromboplastin activator (rt PA) was prospectively evaluated in seven patients with unstable angina and complex angiographic lesions or intracoronary filling defects (ICFD). There were four men and three women, with a mean age of 60 years. Three patients had multivessel disease and all patients had rest angina; none had evolving myocardial infarction. All patients were pretreated with aspirin and were given heparin. IC rt-PA was infused at the rate of 1 mg/min to a total of 50 mg, and angiographic changes were observed every 15 minutes. At 50 minutes, angiographic improvement was seen in two patients (28%), one of whom had complete and one of whom had partial resolution of ICFD. In two patients (28%) there was no change in the lesion, and three patients (42%) had worsening of the lesion appearance. In two of the latter, paradoxical closure was observed at the end of the infusion, and was treated successfully with ad hoc emergency angioplasty. This pilot study suggests that IC rt-PA at the dosage used may have variable effects on complex coronary lesions associated with unstable angina, and this may be of relevance in further trials evaluating IC thrombolysis in unstable coronary ischemic syndromes. PMID- 1905874 TI - Early left ventricular filling: an approach to its multifactorial nature using a combined hemodynamic-Doppler technique. AB - It has recently been shown that early left ventricular filling is a multifactorially determined phenomenon, the characteristics of which are highly dependent on relative changes in any of its determinants (left ventricular end systolic volume, the constant of isovolumic left ventricular pressure decay, left atrial pressure at the onset of mitral valve flow, and left ventricular and left atrial compliance). Thus changes in the pattern of filling do not necessarily reflect changes in diastolic properties; they might instead simply reflect changes in loading conditions. To define a clinically implemented approach where the contribution of each of the covariates of early filling to the filling process and their modification by load manipulation could be assessed, nine patients with ischemic heart disease underwent simultaneous assessment of micromanometer left ventricular pressure and two-dimensional echo-guided Doppler mitral flow velocity before and after administration of nitroglycerin (0.2 mg intravenously). Nitroglycerin induced a significant reduction in the early filling E wave (from 41 +/- 5 cm/sec to 32 +/- 7 cm/sec; p less than 0.002), whereas the late-filling A wave did not change (from 51 +/- 12 cm/sec to 55 +/- 9 cm/sec; p = 0.15), so that the E/A ratio decreased 27 +/- 16% (p = 0.016). End systolic volume, the constant of isovolumic left ventricular pressure decay, and left atrioventricular pressure crossover at the onset of mitral flow decreased (from 49 +/- 37 to 43 +/- 38 ml [p = 0.016], from 52 +/- 14 to 47 +/- 13 msec [p = 0.016], and from 19 +/- 10 to 12 +/- 7 mm Hg [p = 0.08], respectively), whereas left atrial compliance (defined as stroke volume/atrioventricular pressure crossover) and left ventricular compliance (computed as change in volume/change in pressure at early and late diastole) did not change (p = 0.15 and p = 0.38, respectively); the diastolic pressure-volume relationship, however, was displaced slightly leftward and markedly downward, suggesting relief of pericardial constraint. A multilinear regression analysis, performed with pooled data at baseline and during infusion of nitroglycerin in each patient, identified left atrioventricular pressure crossover at the onset of mitral flow as the only significant predictor (p less than 0.02) of peak E wave velocity in the circumstances considered. Thus the interaction among covariates of early left ventricular filling and the relationship between filling and diastolic left ventricular and left atrial properties can be addressed with relative ease by means of this clinically implemented approach, in an effort to sort out the contribution of each cofactor to such a complex event. PMID- 1905875 TI - Incidence of left ventricular thrombi formation after thrombolytic therapy with recombinant tissue plasminogen activator, heparin, and aspirin in patients with acute myocardial infarction. AB - To evaluate the prevalence of left ventricular thrombi after thrombolytic therapy, 144 consecutive patients with acute myocardial infarction (AMI) were prospectively studied with two-dimensional echocardiography 1 and 8 days after admission. Patients were treated 2.1 +/- 0.8 hours after the onset of symptoms. Thrombolytic protocol included 120 mg of recombinant tissue plasminogen activator (rt-PA), 5000 IU of heparin, followed by a continuous infusion of 25,000 IU/24 hours for at least 5 days, and 250 mg of aspirin a day. Seventy-six patients had AMI of the anterior wall; of these, seven (9.2%) developed left ventricular thrombi. The remaining 68 patients had infarctions of the inferior wall; of these, two (2.9%) developed left ventricular thrombi. Since anterior wall infarction not treated with thrombolytic therapy is associated with a 25% to 40% rate of left ventricular thrombi, we conclude that early thrombolytic therapy with rt-PA, heparin, and aspirin reduces the formation of left ventricular thrombus in AMI of the anterior wall. Apical left ventricular thrombi developed more frequently in patients with previous infarctions compared with those without (4 of 17 versus 4 of 127, p = 0.01). During the 12-month follow-up period, no patient in the study had manifestations of peripheral emboli. PMID- 1905876 TI - Safety and cost effectiveness of combined coronary angiography and angioplasty. AB - If coronary angioplasty can be safely performed at the time of the initial diagnostic catheterization, it may result in shorter hospitalization stays and lower overall costs. Combined coronary angiography and angioplasty was performed electively on 733 patients between January 1, 1984, and September 1, 1988. These patients were divided into three major subgroups based upon their indications for angioplasty: 444 (61%) procedures were performed for restenosis; 190 (26%) procedures were performed in patients for unstable angina; and 99 (13%) procedures were performed in patients without unstable angina or previous angioplasty. A subset of 219 patients from this study who underwent elective combined coronary angiography and angioplasty during 1986 were compared with a matched population of 191 patients from the angiography and angioplasty as separate procedures). The success and complication rates were similar for both of these groups. Patients who underwent the combined procedure were hospitalized for a mean of 4.6 days with average total charges of $11,128, compared with 8.0 days and $13,160 for patients undergoing separate procedures (p less than 0.001). Significant savings were also realized with respect to total contrast dose, fluoroscopic time, and total procedural time. Thus in informed patients with suitable coronary anatomy, the strategy of combined angiography and angioplasty may present an opportunity for decreasing hospitalization stay, reducing total charges for revascularization, and reducing radiation exposure without compromising the safety or effectiveness of the procedure. PMID- 1905877 TI - Tandem scanning confocal microscopy (TSCM) of normal and ischemic living kidneys. AB - Tandem Scanning Confocal Microscopy (TSCM) allows one to section optically into and record real-time images of living organs and tissues in a noninvasive fashion. In this paper, we will present some initial TSCM observations of subcapsular nephrons in the living, intact kidneys of Munich-Wistar rats and evaluate the nephron's responses to temporary ischemia and to intravenous infusion of mannitol. The rats were anesthetized with Inactin and a laparotomy performed to expose the kidneys. Using a TSCM equipped with a 20 x water immersion objective, we optically sectioned through the intact kidney capsule and recorded real-time images of living subcapsular glomeruli and uriniferous tubules. The proximal tubule brush border was highly reflective and allowed us to distinguish between the first and second segments of the proximal tubules as well as the distal tubules. Cellular elements of the blood could be seen passing rapidly through peritubular capillaries and individual glomerular capillary loops. With fluorescent filters in place, intravenously injected carboxyfluorescein was seen to pass through the glomerular capillary loops and then progressively through the different segments of the uriniferous tubules. Ligation of the renal artery resulted in rapid swelling of proximal tubule cells into the tubular lumens, loss of reflectiveness of the microvillous brush borders, and closure of the peritubular capillary spaces. Upon release of the ligature, the proximal tubule lumens again became patent, often opening up abruptly and in a zipper-like fashion down the length of the tubules. Increasing the glomerular filtration rate by intravenous infusion of mannitol resulted in increases in tubular luminal and perimeter dimensions. Mannitol also acted as an effective impermeant osmotic agent and prevented most of the cellular swelling which was otherwise seen in response to renal ischemia. PMID- 1905878 TI - A highly polymorphic dinucleotide repeat on the proximal short arm of the human X chromosome: linkage mapping of the synapsin I/A-raf-1 genes. AB - A compound (AC)n repeat located 1,000 bp downstream from the human synapsin I gene and within the last intron of the A-raf-1 gene has been identified. DNA data base comparisons of the sequences surrounding the repeat indicate that the synapsin I gene and the A-raf-1 gene lie immediately adjacent to each other, in opposite orientation. PCR amplification of this synapsin I/A-raf-1 associated repeat by using total genomic DNA from members of the 40 reference pedigree families of the Centre d'Etude du Polymorphisme Humaine showed it to be highly polymorphic, with a PIC value of .84 and a minimum of eight alleles. Because the synapsin I gene has been mapped previously to the short arm of the human X chromosome at Xp11.2, linkage analysis was performed with markers on the proximal short arm of the X chromosome. The most likely gene order is DXS7SYN/ARAF1TIMPDXS255DXS146, with a relative probability of 5 x 10(8) as compared with the next most likely order. This highly informative repeat should serve as a valuable marker for disease loci mapped to the Xp11 region. PMID- 1905879 TI - Three different frameshift mutations of the tyrosinase gene in type IA oculocutaneous albinism. AB - Mutations in the gene for the pigment-producing enzyme tyrosinase are responsible for type IA (tyrosinase-negative) oculocutaneous albinism (OCA). Most reported mutations have been single base substitutions. We now report three different frameshift mutations in three unrelated individuals with type IA OCA. The first individual has a single base deletion within a series of five guanidines, resulting in a premature stop codon in exon I on one allele and a missense mutation at codon 382 in exon III on the homologous allele. The second individual is a genetic compound of two separate frameshift mutations, including both the same exon I single base deletion found in the first individual and a deletion of a thymidine-guanidine pair, within the sequence GTGTG, forming a termination codon (TAG) in exon I on the homologous allele. The third individual has a single base insertion in exon I on one allele and a missense mutation at codon 373 in exon III on the homologous allele. The two missense mutations occur within the copper Bbinding region and may interfere with either copper binding to the enzyme or oxygen binding to the copper. These five different mutations disrupt tyrosinase function and are associated with a total lack of melanin biosynthesis. PMID- 1905880 TI - Efficacy of alternating therapy with oxamniquine and praziquantel to treat Schistosoma mansoni in children following failure of first treatment. AB - Two hundred children infected with Schistosoma mansoni were treated with either 20 mg/kg oxamniquine or 60 mg/kg praziquantel. Cure rates (about 85%) were similar as was the percentage reduction (80%) in egg counts in uncured children. Treatment with the alternative drug of children not cured with the first treatment resulted in negative stools in 11 of 12 cases examined one month after the second round of therapy. In order to minimize the risk of the development of drug resistance, our data suggest that infected patients be treated with one drug, and therapeutic failures with another. Evidence from experiments in mice with isolates obtained after failures of one treatment in children suggests that therapeutic failure does not necessarily indicate the presence of drug-resistant schistosomes. The value of using mice to assess drug resistance in schistosomes is questioned. PMID- 1905881 TI - Monitoring of intestinal transplant rejection. PMID- 1905882 TI - Current concepts of neurocutaneous disorders. AB - The neurocutaneous diseases are a loosely bound group of clinical entities that were initially considered to have dysplastic and/or neoplastic changes of the nervous system and skin, though other organ systems are frequently involved. During the last several decades a variety of additional diseases have been included in this disease category despite their not having any known cutaneous abnormality. The major neurocutaneous syndromes are considered in this review. PMID- 1905883 TI - Fluorescence detection in capillary zone electrophoresis using a charge-coupled device with time-delayed integration. AB - A fluorescence detection system for capillary zone electrophoresis is described in which a charged-coupled device (CCD) views a 2-cm section of an axially illuminated capillary column. The CCD is operated in two readout modes: a snapshot mode that acquires a series of images in wavelength and capillary position, and a time-delayed integration mode that allows long exposure times of the moving analyte zones. By use of the latter mode, the ability to differentiate a species based on both its fluorescence emission and migration rate is demonstrated for fluorescein and sulforhodamine 101. The detection limit for fluorescein isothiocyanate (FITC) is 1.2 X 10(-20) mol; detection limits for FITC amino acids are in the (2-8) X 10(-20) mol range. PMID- 1905884 TI - Comparative performance of 14-crown-4 derivatives as lithium-selective electrodes. AB - A series of neutral ionophore-based lithium-selective liquid-membrane electrodes have been prepared and the electrode performance compared with similar electrodes based on the lithium ionophores ETH 1810-ortho-nitrophenyl octyl ether (oNPOE) and ETH 2137-bis(1-butylpentyl) adipate (BBPA). By using a diamide substituted 14 crown-4 macrocycle, selectivities for Li+ in the presence of Na+ of log kpotLi,Na = -3.25 and -2.92 were obtained for diisobutylamide-oNPOE and di-n-butylamide oNPOE derivatives. The di-n-butylamide-oNPOE based electrode functioned satisfactorily in serum, exhibiting a fast response time (10-15 s), an acceptable lifetime of 50 d and minimal protein interference. PMID- 1905885 TI - Influence of changes in arterial carbon dioxide tension on the electroencephalogram and posterior tibial nerve somatosensory cortical evoked potentials during alfentanil/nitrous oxide anesthesia. AB - The effects of variation of arterial CO2 tension (PaCO2) on the electroencephalogram (EEG) and posterior tibial nerve somatosensory cortical evoked potentials (PTN-SCEP) during opioid/N2O anesthesia have not been well documented. We studied the effects of hypocapnia (PaCO2 approximately 23 mmHg) and hypercapnia (PaCO2 approximately 50 mmHg) during steady-state alfentanil/N2O anesthesia in 16 patients. EEG and PTN-SCEP were recorded continuously, while PaCO2 was altered in 15-min intervals by varying the inspired CO2 concentration. Hypocapnia caused significant increases in power in the delta, theta, and beta bands (P less than 0.01), with the greatest increase observed in the alpha band. Relative power increased in the alpha band but remained unchanged in the delta, theta, and beta bands. Median frequency and 95% spectral edge frequency were unaltered during hypocapnia. In contrast, hypercapnia caused a significant decrease of power in the alpha and beta bands, whereas delta and theta power remained unchanged. This was reflected in a significant decrease of the 95% spectral edge frequency, from 8.9 (6.7-11.6) to 7.0 (5.6-8.6) Hz. All EEG parameters returned to normal upon restoration of normocapnia. There was a significant negative correlation between power in the alpha band and end-tidal CO2 in all patients (r = 0.47 to -0.89). PTN-SCEP latencies and amplitudes were not significantly different from control values during hypocapnia and hypercapnia. It is concluded that variations in PaCO2 within the limits 20-50 mmHg produce substantial changes in the EEG power spectrum, especially in the alpha band (8-12 Hz), but do not alter PTN-SCEP. PMID- 1905886 TI - Confirmation of endotracheal tube placement: a miniaturized infrared qualitative CO2 detector. AB - STUDY OBJECTIVES: A miniaturized, infrared, solid-state, end-tidal CO2 detector was used to confirm emergency endotracheal tube (ETT) placement. DESIGN: This prospective, clinical study used a miniature, infrared, solid-state end-tidal CO2 detector to confirm ETT placement in an acute setting. SETTING: The ICU, emergency department, and hospital floor. TYPE OF PARTICIPANTS: There were 88 consecutive adult patients requiring 100 emergency intubations. MEASUREMENTS AND MAIN RESULTS: The indication for airway intervention was considered urgent in 79% and under arrest conditions in 21%. The mean number of intubation attempts was 1.83 (range, one to five) with difficulty of intubation of 6.48 and confirmation of 7.75, on a linear scale from 0 (lowest) to 10 (highest). Determination of ETT position revealed intratracheal intubation in 96% and esophageal intubation in 4%. Placement was confirmed by direct visualization or radiography in all cases. Sensitivity and specificity for ETT localization was 100% (P less than .0001). CONCLUSION: This hand-held infrared capnometer reliably confirms ETT placement under emergency conditions. PMID- 1905888 TI - Gastrostomy tube transmigration: a rare cause of small bowel obstruction. AB - A 77-year-old woman with an indwelling gastrostomy tube presented with a clinical picture of pneumonia and small bowel obstruction. During gastrostomy closure and performance of a feeding jejunostomy, inadvertent transmigration of the gastrostomy tube was found to be the etiology of the small intestinal obstruction. This case illustrates a rare complication of enteric feeding tubes. PMID- 1905887 TI - Cerebral dural sinus thrombosis. AB - Cerebral dural sinus thrombosis is an unusual syndrome in which a patient presents with a severe headache that may be associated with diverse neurologic and physical findings. The case of a 31-year-old woman with headache, vomiting, generalized tonic-clonic seizure, and subsequent dense hemiplegia is presented. The patient was diagnosed as having a cerebral dural sinus thrombosis, but only after the diagnosis was missed initially. The syndrome may be difficult to detect because it can mimic several other entities. There are several known or suspected predisposing factors. The syndrome, diagnostic modalities, and therapeutic options are reviewed. PMID- 1905889 TI - Hypercarbic ventilatory responses of human heart-lung transplant recipients. AB - To evaluate the effects of chronic pulmonary denervation on ventilatory control, we compared the hypercarbic ventilatory responses (HCVR) of 12 human heart-lung transplant recipients (HL) and 24 normal control subjects (C). The six male HL were subsequently compared with eight male heart transplant recipients (H), as well as the 12 male C. All subjects had normal spirometry, but lung volumes of both transplant groups were somewhat less than those of C. The HCVR of HL and C were indistinguishable (2.68 +/- 0.28 versus 2.71 +/- 0.22 L/min/mm Hg, respectively). The increment of mouth occlusion pressure (delta Pm0.1/delta CO2), however, was markedly greater in HL (P much less than 0.01). The three male groups also had equivalent HCVR, and again, the HL had an increased delta Pm0.1/delta CO2. HL men exhibited larger increments of VT and decreased frequency responses during CO2 rebreathing than did male C and H, although these differences were statistically significant only in the comparison between the transplant groups. We conclude that HL with normal spirometry have appropriate HCVR, despite pulmonary denervation. Pm0.1 responses of these subjects are increased, however, reflecting either a compensatory response to greater respiratory impedances or an occult alteration of ventilatory mechanics. Moreover, compared with subjects with similar pulmonary function, e.g., heart transplant recipients, the breathing pattern of HL during progressive hypercarbia is consistent with the absence of vagal-mediated inflation inhibition. PMID- 1905890 TI - Rewash bronchoalveolar lavage. AB - A significant limitation of standard bronchoalveolar lavage (BAL) technique is the inability to measure or calculate epithelial lining fluid (ELF) volume and, therefore, in vivo concentrations of substances in the ELF. We evaluated a new rewash BAL procedure with the radiolabeled tracer technetium pertechnetate (99mTcO4-) that theoretically should be immune to even exaggerated fluid shifts during BAL. To test this theory, we measured ELF volume in control sheep using isosmotic (280 mosm/L) hypoosmotic (140 mosm/L) and hyperosmotic (570 mosm/L) BAL solutions to induce exaggerated fluid shifts during the lavage procedure. The mean ELF volume of the lavaged lung segment was not significantly different for the three solutions (isosmotic, 1.7 +/- 0.8 ml; hypoosmotic, 1.1 +/- 1.2 ml; hyperosmotic, 2.1 +/- 1.6 ml). The slope of the 99mTcO4- disappearance curve, however, was significantly steeper for the hyperosmotic solution (-0.40 +/- 0.04%/min) compared with the other solutions (isosmotic, -0.14 +/- .01%/min; hypoosmotic, -0.12 +/- 0.07%/min). Calculation of ELF volume using sodium as an endogenous tracer gave consistently smaller values with each of the mannitol solutions (isosmotic, 0.21 +/- 0.30 ml; hypoosmotic, 0.02 +/- 0.03 ml; hyperosmotic, 0.18 +/- 0.18 ml). The failure of sodium to provide accurate estimates of the ELF volume may be due to complicated sodium movement in the lung and errors in our assumption of the initial concentration of sodium in the ELF fluid. We conclude that the rewash BAL technique with 99mTcO4- gives values of ELF volume that are not significantly affected by even exaggeration of the fluid flux that invariably accompanies BAL. PMID- 1905891 TI - Successful treatment of steroid-resistant double-lung allograft rejection with Orthoclone OKT3. AB - An 18-yr-old woman with cystic fibrosis who received a double-lung transplant developed a severe episode of acute lung rejection. Bronchoalveolar lavage and transbronchial biopsy were used to establish the diagnosis. The rejection was refractory to administration of high-dose pulse steroids. OKT3 therapy was successfully used to reverse this episode. This is the first case report of a steroid-resistant double-lung allograft rejection successfully treated with OKT3. PMID- 1905892 TI - Airway blood flow modifies allergic airway smooth muscle contraction. AB - We tested the hypothesis that airway perfusion modifies the contractile response of airway smooth muscle to allergen challenge by influencing the clearance of locally released spasmogens. In six intact, lightly sedated, sheep allergic to Ascaris suum, we measured tracheal mucosal blood flow (Qtr) with a soluble gas uptake method and tracheal dead space (Vtr), an index of airway smooth muscle tone, by helium dilution before and serially after local aerosol challenge with A. suum extract or ragweed extract (control). The former challenge was repeated during continuous intravenous infusion of either vasopressin or nitroglycerin, which by themselves had no effect on Vtr and decreased and increased Qtr, respectively. Ragweed had no effect on Qtr and Vtr, whereas A. suum increased mean (+/- SE) Qtr by 111 +/- 31% (p less than 0.05) and decreased mean Vtr by 15 +/- 2% (p less than 0.05) immediately after challenge, with Qtr returning to baseline by 40 min and Vtr by 80 min. Vasopressin infusion prevented the A. suum induced increase in Qtr and prolonged the decrease in mean Vtr (p less than 0.05). During nitroglycerin infusion, A. suum failed to alter Qtr or Vtr. Vasopressin and nitroglycerin had no effect on the contractile responses of tracheal smooth muscle to A. suum in vitro. These results indicate that the effects of vasopressin and nitroglycerin on antigen-induced airway smooth muscle contraction in vivo were due to alterations in airway blood flow rather than to alterations in the release of or airway smooth muscle responsiveness to chemical mediators. PMID- 1905893 TI - Endometrial receptivities after leuprolide suppression and gonadotropin stimulation: histology, steroid receptor concentrations, and implantation rates. AB - The effect of markedly supraphysiologic levels of E2 and P4 on the endometrium was assessed by examining endometrial histology, E2 and P4 receptor concentrations, and embryo implantation rates in IVF cycles with and without leuprolide use. Results suggest that 1) the high ovarian response common in leuprolide pretreated cycles can advance endometrial histology, but only up to a certain limit, 2) P4 greater than 25ng/ml or E2 greater than 200pg/ml on the day of transfer was associated with non-lagging endometria, 3) implantation rate in high response cycles is not impaired and may be increased, 4) earlier P4 supplementation in low response cycles may be beneficial, 5) extraordinarily high response (E2 greater than 5000pg/ml) may be detrimental to implantation, and 6) the optimal histology for implantation appears to be at least day 16. PMID- 1905894 TI - Tissue factors influencing growth and maintenance of endometriosis. AB - The unpredictable response of endometriosis to steroids and its recurrence after therapy, led us to hypothesize a possible further control of this pathology by factors other than steroids. The presence of estrogen, progesterone and epidermal growth factor receptors (ER, PR, EGFr) was evaluated using immunohistochemistry before and after therapy with Danazol or a gonadotropin-releasing hormone analogue (GnRHa), Buserelin. EGFr, ER and PR were present in 100% of endometrial specimens, and in 71%, 29% and 49% of endometriotic implants, respectively. Danazol and GnRHa reduced immunohistochemical staining for EGFr antisera in the endometrial and endometriotic specimens. About 21% of endometriosis were EGFr positive and ER negative, suggesting a potential role of epidermal growth factor in growth and maintenance of endometrial ectopia. PMID- 1905895 TI - Tamoxifen-stimulated growth of human endometrial carcinoma. AB - An estrogen receptor and progesterone receptor positive endometrial carcinoma (EnCa101) will grow in response to either estradiol or tamoxifen when transplanted into athymic mice. We have tested several antiestrogens with different properties to determine their ability to support endometrial tumor growth. Trioxifene, enclomiphene and nafoxidine are all as active as tamoxifen whereas the antiestrogen keoxifene, that has reduced estrogen-like properties, will partially inhibit tamoxifen-stimulated growth. Furthermore, the pure antiestrogen ICI 164,384 will block tamoxifen-stimulated growth without having any effect itself on tumor growth rate. Overall, the ability of antiestrogens to stimulate the growth of human endometrial carcinoma EnCa101 appears to be related to their intrinsic estrogenic activity. PMID- 1905896 TI - Nonsteroidal antiinflammatory drugs. PMID- 1905897 TI - Neutrophil proteinases. Caution signs in designing inhibitors against enzymes with possible multiple functions. PMID- 1905898 TI - [Pigmented nevus and cutaneous ossifications. Apropos of 125 cases of osteonevi]. AB - In a series of 86,400 pathological examinations 125 cases of pigmented naevus associated with one or several foci of cutaneous ossification were observed. This association, known as osteonaevus of Nanta, account for 1.4 p. 100 of all pigmented naevi. In our series of examinations, osteonaevus was the most frequent cause (62 p. 100) of the 201 skin ossifications observed, the other causes being keratinizing basal cell epithelioma (7 p. 100) and pilomatricoma (5.5 p. 100). The patients' mean age was 46 years (range: 21-80 years), and 81 p. 100 of them were women. In almost every case the lesions were located on the head. The clinical diagnosis was always pigmented naevus, but it coexisted with inflammatory changes in 8 cases, and an underlying induration could be perceived at palpation in 4 cases. In 123 or ou 125 cases the pigmented naevus was restricted to the dermis, junctional theques being present in only 2 cases. The number of ossified foci varied from 1 in 45 p. 100 of the cases to 2 to 4 in 91 p. 100, and in 1 patient up to 8 foci were visible on the same section plane. The lesions presented as compact balls (135 cases), or lamellated bone (126 cases), or spicules of unorganized bone formations. They varied in size from 0.5 mm for balls to 1.5 mm for elements with a central cavity. In the latter were rudiments of bone marrow with capillary vessels, osteoclasts, adipose cells and cells that could be regarded as having haemopoietic functions. All naevi contained hair follicles.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1905899 TI - Effects of irradiation on red cells stored in CPDA-1 and CPD-ADSOL (AS-1). AB - Red blood cells (pRBC) collected in citrate, phosphate, dextrose, adenine-formula 1 (CPDA-1) and citrate, phosphate, dextrose-adenine, manitol saline solution (CPD ADSOL [AS-1]) anticoagulants are increasingly being stored for variable periods in transfusion service inventories following irradiation. While anecdotal reports of increased K+ following irradiation and storage have recently appeared in the literature, concomitant in vitro biochemical changes resulting from differences in anticoagulants have not been reported. Utilizing two venipunctures, two units each of 225 mL of blood from five volunteers were collected in anticoagulant adjusted CPDA-1 and AS-1 bags. Within two hours of collection, each unit was equally divided. One of each pair was irradiated (2000 rads). Samples were analyzed on Days 0, 1, 3, 7, and every seven days to expiration. Irradiation resulted in a 2.3 fold increase in K+ during the first seven days of storage for both anticoagulants, although significantly greater K+ levels were observed in the CPDA-1 pairs compared to the AS-1 pairs. Comparison of glucose utilization, plasma free hemoglobin, 2,3-diphosphoglycerate (2,3-DPG) and lactate dehydrogenase between control and irradiated CPDA-1 and AS-1 pairs and between anticoagulants were documented. PMID- 1905900 TI - Relation between carcinogenesis, chromatin structure and poly(ADP-ribosylation) (review). AB - Poly(ADP-ribose) is a naturally occurring nuclear macromolecule resembling nucleic acids. It is synthesized from NAD+ on histones and a few other nuclear proteins. Its function, although not completely understood, might be to alter chromatin structure and to regulate the activity of proteins involved in the metabolism of DNA strand breaks such as ligase II, and topoisomerase I. In addition, poly(ADP-ribose) modifies proteins involved in gene expression such as acetylated histones. HMG proteins, and T antigen. The enzyme poly(ADP-ribose) polymerase responsible for this modification has the unique property of requiring nicks or free ends on the DNA for its activity and of being automodified. The automodified enzyme, presumably found at the vicinity of DNA strand breaks at damaged chromatin sites, could remove histones from DNA and attract enzymes that have an affinity for poly(ADP-ribose) such as ligase II or poly(ADP-ribose) glycohydrolase, the polymer-degrading enzyme. Alterations in chromatin structure alter gene expression and seem to be involved in repair, replication, and recombination and in changing DNA superhelical density, intermediate steps in molecular carcinogenesis. Experiments with cells in culture and laboratory animals show that inhibition of poly(ADP-ribosylation) alters transformation and tumorigenicity brought about by a great number of carcinogenic agents. Cancer can be caused by the accumulation of unrepaired DNA strand breaks in the cell accelerating gene rearrangements, deletions, insertions and amplifications. Repair of DNA strand breaks shows an absolute dependence upon the rapid synthesis and degradation of poly(ADP-ribose). The polymer has a very short half life indeed. Data are reviewed on changes in chromatin structure and function caused by histone and nonhistone poly(ADP-ribosylation). The link of this modification to transformation, tumorigenesis, development, replication and gene expression is examined. A model is proposed to explain the effect of poly(ADP-ribosylation) on chromatin structure at the molecular level. Mono- and oligo(ADP-ribosylated) histones present in nuclei under physiological conditions are proposed to functions, like acetylated histones, in maintaining chromatin loops into transcriptionally active structures. On the other hand, poly(ADP-ribosylated) histones and poly(ADP-ribosylated) enzymes such as DNA and RNA polymerases, suggested to be modified from in vitro studies, might only appear in cells that have been heavily damaged by carcinogen. Their function might be to remove histones from DNA in order to facilitate repair and to shut down transcription and replication. PMID- 1905901 TI - Influence of thiols and inhibitors of prostaglandin biosynthesis on the carcinogen-induced development of mammary lesions in vitro. AB - Mouse mammary gland undergoes physiological changes, comparable to that in the animal, under appropriate hormonal conditions in organ culture. Moreover, they form mammary lesions when exposed to the carcinogen, dimethylbenz(a)anthracene (DMBA) for a short duration. This organ culture system was utilized in the present of study to evaluate activity of two groups of potential chemopreventive agents. Activity of inhibitors of prostaglandin synthesis and thiols was determined at five concentrations. The average incidence of mammary lesions induced by DMBA was 60%, oltipraz oxithiazolidine, thioctic acid and N acetylcysteine were effective at different concentrations, whereas diallyldisulfide, sulfasalazine and ajoene were marginally effective. Within the inhibitors of prostaglandin synthesis category, aspirin, ibuprofen and indomethacin were effective, whereas dipyridamol, piroxicam and pentoxyphyllin were ineffective. The results correlated well with the known in vivo effects of these agents on chemically induced carcinogenesis of mammary gland. The study provides evidence for the use of mammary gland organ culture as a screening total system for prediction of effective chemopreventive agents against mammary carcinogenesis. PMID- 1905902 TI - Characterization of effective chemopreventive agents in mammary gland in vitro using an initiation-promotion protocol. AB - Mouse mammary glands respond to carcinogen stimulus to form mammary lesions in organ culture. Prevention of the formation of mammary lesion has been utilized as a test to evaluate the effectiveness of a variety of classes of agents. In the present study we determined whether the effective chemopreventive agents are active against initiation or the promotion phase of lesion development. Mammary glands were subjected to 24 hours exposure to 2 mg/ml dimethylbenz (a) anthracene (DMBA) followed by a 5 day exposure to 7,12-tetradecanoyl phorbol - 13 - acetate (TPA). This treatment protocol allows one to study initiation and promotion aspects of lesion development. Chemopreventive agents effective when present prior to the carcinogen were considered as anti-initiators, whereas agents effective when present after the DMBA treatment along with TPA were considered as anti-promoters. Within the chemopreventive agents evaluated, limonene, oltipraz, aspirin, curcumin and b-sitosterol were anti-initiators. Esculatin, thiolutin, silymarin, DHEA and a few others were found to be anti-promoters. Results presented in this report can be utilized to study the efficacy of these agents in vivo. PMID- 1905903 TI - Evidence for the functional similarity between tumour cell surface guanidinobenzoatase and tissue type plasminogen activator. AB - Tumour cells possess a cell surface protease referred to as guanidinobenzoatase (GB). The active centre of GB binds the fluorescent probe 9-amino acridine (9-AA) and this binding enables cells possessing active GB to be located by fluorescent microscopy. GB binding of 9-AA was inhibited by prior treatment of sections of tumour tissue with a specific polyclonal antibody recognising the tumour associated protease tissue plasminogen activator (t-PA). GB binding of 9-AA was also inhibited by prior treatment of sections of tumour tissues with PAI-I, a protein inhibitor of plasminogen activatory. We conclude from these studies and kinetic analyses that GB and t-PA are very similar both in structure and function. PMID- 1905904 TI - Effects of treatments with alpha-difluoromethylornithine and hyperthermia on the growth and polyamine metabolism of Harding-Passey murine melanoma. AB - The oral administration of alpha-difluoromethylornithine (DFMO), an enzyme activated inhibitor of ornithine decarboxylase (ODC), produced a marked decrease in the rate of growth of amelanotic Harding-Passey melanoma transplanted in mice. The half-life of this compound in Harding-Pasey melanoma was 30 min. A combined treatment of DFMO and hyperthermia did not show any synergistic effect on the inhibition of tumor growth, and no differences in the levels of tumor ODC, S Adenosylmethionine decarboxylase (SAMDC) and polyamines were observed between single and combination treatments. DFMO-treatment alone produced a decrease of about 80% in spermidine concentration in melanoma, while in other tissues such as kidney, the diminution of spermidine was only moderate. ODC activity was reduced greatly in the kidney and moderately in melanoma. However, the activity of SAMDC increased up to 30-fold in DFMO-treated melanoma, while only a moderate increase was observed in the renal enzyme. Melanoma tyrosinase activity did not increase with the treatment with DFMO. These results indicate that the inhibition of amelanotic Harding-Passey melanoma growth by DFMO is not caused by the stimulation of cell differentiation, and that in this system polyamine depletion caused by this drug does not produce an enhancement in the heat-induced cytotoxicity. PMID- 1905905 TI - Antitumor activity of 2-mercaptoethanesulfonate (mesna) in vitro. Its potential use in the treatment of superficial bladder cancer. AB - 2-Mercaptoethanesulfonate (mesna) is a nontoxic drug which upon intravenous and oral administration effectively prevents urothelial toxicity in cancer patients treated with oxazaphosphorines. Mesna is rapidly oxidized to dimesna in the blood. It is then taken up by kidney tubular cells in which it is reduced and excreted into the urine as mesna where it reacts with toxic metabolites. We have observed that mesna, but not dimesna, may inhibit growth of several human malignant cell lines in vitro. Some are extremely sensitive, whereas others are more or less resistant. It was found that 2/4 relatively resistant human bladder cancer cell lines turned sensitive upon repeated administrations of mesna and 5/5 cell lines appeared to be sensitive to mesna when grown in serum-free medium. The results seem to provide an explanation of the remarkable positive clinical effects of prolonged oral mesna treatment in patients with superficial bladder cancer. PMID- 1905906 TI - Size and frequency of the DNA fragments in the rearranged immunoglobulin heavy chain joining regions in the lymphocytic leukemias. AB - Four distinct groups of DNA fragments produced by the rearrangement of the joining regions of the immunoglobulin heavy chain gene were found after hydrolysis of the leukemic DNA with the EcoR I restriction enzyme. Three fragments were smaller than the genomic fragment (16 kb) and their average sizes were 9.6, 11.2, and 13.7 kb. The largest fragment was 18.7 kb. The fragment groups 2 and 3 (11.2 and 13.7 kb) were found in 65 per cent of the cases. There was no correlation between the fragment groups and the acute or chronic lymphocytic leukemia or B-cell lymphoma. PMID- 1905907 TI - Inhibition of DNA synthesis and oncogene expression in tumor cells by the biological factor DIF. AB - A regulatory factor isolated from the maternal part of bovine placentas (decidua inhibitory factor, DIF) inhibits the incorporation of thymidine into the DNA of a variety of animal and human tumors. The degree of inhibition is dependent on the concentration of the factor. Results indicate that signal transduction occurs via a Ca2+ mobilizing pathway after specific binding of the inhibitor to tumor cell surface receptors. On of the main consequences of DIF action is the inhibition of c-fos and c-myc expression and/or degradation. PMID- 1905908 TI - Cytochrome P-450 metabolism of arachidonic acid. AB - The cytochrome P-450 pathway of AA metabolism is widely distributed and gives rise to a diversity of products affecting basic biological mechanisms such as vascular reactivity and transport function in critical nephron segments. P-450-AA metabolites may participate in receptor-mediated signal transduction and may act as second messengers. The synthesis of P-450-AA products can be altered by pharmacologic probes and is affected by pathophysiological conditions. That this review has centered on the circulation and renal function should not be interpreted as minimizing the importance of P-450-AA metabolites in other organs and systems for, most assuredly, they will be shown to constitute an essential component of organ function in sites other than those addressed here. PMID- 1905909 TI - Neurofibromatosis. PMID- 1905910 TI - [Carcinoma and renal schistosomiasis]. AB - A case of a patient with renal schistosomiasis and clear cell renal carcinoma involving the same organ is reported herein. To our knowledge, the foregoing association has not been reported in the literature. PMID- 1905911 TI - Nutritional management of catabolic acute renal failure requiring renal replacement therapy. AB - Catabolic acute renal failure patients have a high incidence of morbidity and mortality despite advances in dialytic and lifesaving technologies. Malnutrition is a complicating factor in the treatment of these patients. Early and aggressive nutritional support may positively impact eventual outcome. Continuous renal replacement therapy (CRRT) enables delivery of this support. This article reviews nutritional support in acute renal failure for individuals undergoing these therapies. PMID- 1905912 TI - Composition of fat in enteral diets can influence outcome in experimental peritonitis. AB - An animal model of protracted acute peritonitis was used to study the effects on survival of different amounts and types of dietary fat. Guinea pigs (n = 132) were provided with gastrostomies and allowed to recover. Intraperitoneal osmotic pumps were then placed, allowing for effusion of viable bacteria during the next week. Three days after pump implantation, the animals were randomized to receive one of nine diets, differing only in fat content (3.5%, 14%, or 56% of total calories) and fat composition (100% Microlipid [primarily safflower oil, rich in linoleic acid], 100% MaxEPA [fish oil containing 35% omega-three fatty acids], or a 50:50 mixture of both oils). At the end of 2 weeks, survival rates were compared. Among all types of fat used, the level of fat did not affect outcome, with survival rates of 13% (6 of 45) at the low level of fat used, 30% (13 of 44) at the medium level, and 26% (11 of 43) at the high level (P greater than 0.10). However fat composition significantly influenced survival across all levels of fat, with a 39% (17 of 44) survival rate in the groups given equal amounts of Microlipid and MaxEPA, compared either to 21% (9 of 44) for the 100% Microlipid groups, or to 9% (4 of 44) for the 100% MaxEPA groups (p less than 0.05). A second experiment was performed with 58 animals fed five different mixtures of fats, all at 14% of total calories. Diets were made with fat ratios of 100:0, 75:25, 50:50, 25:75, and 0:100 Microlipid to MaxEPA. The survival rate in the 50:50 group was 83% (10 of 12), which is significantly higher than the survival rates with any of the others (p less than 0.05). It is concluded that the amount of fat in the diet does not strongly influence outcome in this model. However an equal mixture of safflower and fish oils significantly improves survival rates compared to diets made with single-oil preparations. PMID- 1905913 TI - Anti-tumor effect of L-methionine-deprived total parenteral nutrition with 5 fluorouracil administration on Yoshida sarcoma-bearing rats. AB - L-methionine-deprived total parenteral nutrition (methionine-deprived TPN), infusing amino acid solution devoid of L-methionine and L-cysteine by the method of TPN as an only protein source, showed enhancement of the effect of several anti-cancer agents. In this study the combined effect of the methionine-deprived TPN with administration of 5-fluorouracil (5-FU) was examined in Yoshida Sarcoma (YS)-bearing rats, from aspects of effects on the tumor metastasis and the host animal's life span, in the following four groups treated with: methionine deprived TPN with administration of 5-FU, methionine-deprived TPN without administration of 5-FU, L-methionine-contained TPN plus 5-FU, and L-methionine contained TPN without 5-FU. In the first experiment, TPN was continued for 8 days in the four groups, and the anti-cancer effect of methionine-deprived TPN and administration of 5-FU based on both the growth of the primary tumor at the implanted site and the tumor metastasis was studied from the view point of pathologic findings of animals killed immediately after these treatments. In experiment 2 the survival period was examined after these treatments for 10 days with subsequent oral feeding until death. The results were as follows: proliferation of YS, transplanted subcutaneously, was markedly suppressed; particularly hematogenous metastasis, characteristic in YS, was prominently blunted then obtained an apparent longer survival period in rats treated with the methionine-deprived TPN with administration of 5-FU. PMID- 1905914 TI - [Acute myocardial infarction: immediate coronary angioplasty for failure or contra-indications of thrombolytic therapy. Apropos of a series of 100 cases]. AB - One hundred patients admitted to a centre of interventional cardiology with acute myocardial infarction of less than 6 hours, underwent coronary angioplasty of first intention because of contra-indications to thrombolytic therapy (n = 20) or after thrombolytic therapy with streptokinase (n = 54), acylenzymes (n = 12) or tissue type plasminogen activator (n = 14). The indication of angioplasty were those of the TIMI (Thrombolysis in Myocardial Infarction) classification (occluded artery, TIMI grade 0) (n = 60) (suboccluded artery, TIMI grade 1) (n = 40). The criterion of success of angioplasty was an increase greater than 1 of TIMI grade. Reperfusion of the coronary artery was obtained by angioplasty in 95% of failures of thrombolysis and in 90% of patients with contra-indications to thrombolytic therapy. The early reocclusion rate at D1 was 2%. Repeat angioplasty at D1 was successful in both these cases and the arteries were still patent at D21. The reocclusion rate at the third week in 75 patients who underwent control coronary angiography was 5.3%. In patients with arterial occlusion, immediate angioplasty attained two objectives in the same procedure: a high rate of emergency myocardial reperfusion and a low rate of reocclusion. The average left ventricular ejection fraction (all arteries) significantly improved (+9.2% in absolute values) when the artery remained patent (p less than 0.001), especially when the initial ejection fraction was low. In the patients who had occluded arteries at control angiography at 3 weeks, the ejection fraction decreased (-4% in absolute values) (NS). The following complications were observed: 4 coronary artery dissections and haematomas at the site of femoral puncture in patients who had received thrombolytic therapy (10 drained surgically). The hospital mortality was 3% and global mortality after an average follow-up period of 19.6 months was 5%. Coronary angioplasty in acute myocardial infarction carries a low risk and seems to be beneficial in patients with contra-indications to or failure of thrombolysis. PMID- 1905915 TI - [Temporary caval filter allowing diagnosis and fibrinolytic therapy in patients suspect of massive pulmonary embolism]. AB - The authors propose a therapeutic strategy enabling diagnosis, treatment and prevention in the same clinical procedure based on a series of 8 patients presenting with signs of massive pulmonary embolism (acute cardiorespiratory distress, shock, loss of consciousness, and/or cardiac arrest). A removable vena cava filter is rapidly introduced percutaneously via a brachial, femoral or jugular vein, and opened in the inferior vena cava. Using the same catheter and without a second venous puncture, pulmonary angiography and cavography are performed by digitised angiography using a small quantity of contrast medium (40 ml, 12 ml/sec). The diagnosis of massive pulmonary embolism (index of pulmonary obstruction 70 to 90%) was confirmed in 6 out of the 8 cases. In 2 patients, the contrast medium passed from the right atrium into the left atrium and one of the patients developed hemiplegia. Thrombolytic drugs (rt-PA followed by Streptokinase) were injected via the same filter catheter. The dosage of rt-PA was 20 to 50 mg as a bolus followed by 50 mg in 2 hours. Streptokinase was then infused at a dose of 100,000 U/hour for an average of 36 hours (24-48 hours), followed by intravenous heparin and oral vitamin K antagonists. Two patients required blood transfusion for haemorrhage during the relay with heparin. The temporary caval filter was removed in all cases but 3 patients required a definitive filter because of the persistence of life-threatening venous thrombosis. Seven of the 8 patients survived their pulmonary embolism. This approach is rapid, saves time, and spares the patients from more invasive procedures. PMID- 1905916 TI - [Bilateral renal embolism during thrombolytic therapy with tissue-type plasminogen activator in a patient with thrombosis of the left ventricle]. AB - The authors report a case of bilateral renal embolism during thrombolytic treatment in the acute phase of myocardial infarction in a 77 year old patient in whom echocardiography had shown a left ventricular thrombus. After reviewing the literature, the risk of embolic complications of thrombolytic therapy would seem difficult to evaluate because of the difficulty of diagnosis, but they exist irrespective of the type of thrombolytic agent used. PMID- 1905917 TI - Screening corneal donors for transmissible disease. Safety, resources, and reason. PMID- 1905918 TI - The value of cordocentesis in management of patients with severe preeclampsia. AB - Severe preeclampsia affects placental function and causes fetal compromise. It is necessary to deliver the fetus at an appropriate time in order to minimize fetal mortality and morbidity. Cordocentesis was performed in 9 patients with severe preeclampsia (group 1) and 10 patients with other pregnancy complications (group 2). Intrauterine growth retardation occurred in 5 patients in group 1 and in only one patient in group 2. Blood gas parameters including pH, pO2 and O2 saturation were significantly lower for group 1, while pCO2 was significantly higher, as compared to group 2. For patients in group 1, non-invasive fetal surveillance successfully identified 5 patients with fetal compromise, who required immediate termination of pregnancy. All 5 of these patients had abnormal fetal blood gas analyses by cordocentesis. Fetal blood gas analysis was abnormal in 2 additional fetuses among the remaining 4 patients who exhibited normal findings by non invasive methods of fetal surveillance. These results suggest that cordocentesis is useful in identifying fetal compromise (fetal hypoxia/acidosis) prior to the onset of labor in high-risk patients, such as preeclampsia associated with intrauterine growth retardation. PMID- 1905919 TI - [Electron microscopic virus diagnosis in dogs, cats, calves, swine and foals in the year 1989]. AB - During 1989 fecal and gut samples of 598 dogs, 189 cats, 496 calves, 100 pigs and 66 foals with diarrhoea were investigated for virus by electron microscopy. In samples of dogs and cats Parvovirus was detected in 18.5% and 8.5% of the samples, respectively; Coronavirus was found in 14.9% and in 16.4% of the specimens. In samples of calves Coronavirus dominated with a detection rate of 37.5%, followed by Rotavirus with 10.7% and not clearly identifiable particles resembling Coronavirus (4.2%). In 7.1% of the specimens Rotavirus as well as Coronavirus was found. In 33% of specimens from piglets Coronavirus was detected. 10.6% of the faeces from foals contained Coronavirus-like particles. Between 1987 and 1989 the detection rate of Parvovirus in faeces from dogs and cats decreased from 24.2% to 18.6% and from 17.5% to 8.5%. Coronaviruses in calves, dogs and cats increased from 22.9% to 37.5%, from 5.6% to 14.9% and from 8.2% to 16.4% of the samples investigated. PMID- 1905920 TI - Role of serine biosynthesis and its utilization in the alternative pathway from glucose to glycogen during the response to insulin in cultured foetal-rat hepatocytes. AB - The role of serine as a possible intermediate of the alternative pathway from glucose to glycogen was investigated under basal and insulin-stimulated conditions in 18-day cultured foetal-rat hepatocytes because these cells cannot use pyruvate-derived metabolites [Bismut & Plas (1989) Biochem. J. 263, 889-895]. Incubation of cells with [U-14C]glucose for 24 h led to a release of labelled serine in the medium concomitantly with a net serine production (100 nmol/24 h per culture). The rate of [14C]serine formation (close to 3 nmol/h per culture) indicated that a large part of newly formed serine originated from glucose. When short-term experiments were performed at day 2, glycogen labelling from [U 14C]serine or [U-14C]glycine, which was increased 3-fold by insulin after 2 h, evidenced their participation as glycogenic precursors. When a double-isotope procedure with [U-14C,3-3H]glucose was used, the direct and the alternative pathways from glucose were found to contribute to glycogenesis by 75 and 25% respectively. Cycloserine (18 mM), a transaminase inhibitor, strongly inhibited glycogen labelling from [U-14C] serine while producing a 70% increase in glucose incorporation by the alternative pathway, in both the presence and the absence of insulin. The inhibitor had no effect on the direct pathway from glucose to glycogen. Supplementation with 1 mM-hydroxypyruvate, a serine-derived metabolite, did not affect direct glucose incorporation, whereas the alternative pathway was stimulated whether insulin was present or not. These results indicate that the sequence glucose----serine----glycogen is operative in cultured foetal hepatocytes. The alternative pathway interferes with hydroxypyruvate utilization, and is likely mediated by the serine aminotransferase pathway, independently of the acute glycogenic action of insulin. PMID- 1905921 TI - Purification and properties of a neurotensin-degrading endopeptidase from pig brain. AB - Neurotensin (NT) endopeptidase (EC 3.4.24.16) has been purified about 800-fold from pig brain by four sequential chromatographic steps depending on ion-exchange and hydrophobic interactions. Two types of preparation were studied: one from a Triton X-100-solubilized membrane fraction, and the other from the soluble fraction containing 90% or more of the total activity in the homogenate. NT endopeptidase activity was monitored by high-precision liquid chromatography of the two peptide products, characterized as NT-(1-10) and NT-(1-8), resulting from cleavage of the Pro10-Tyr11 and Arg8-Arg9 bonds respectively. As purification proceeded, from both membranes and cytosol, the yield of the two products achieved a constant ratio of 5:1 and this ratio was reproduced in repeated purifications. However, a distinct peptidase which hydrolysed exclusively at the Arg8-Arg9 bond was partially resolved from NT endopeptidase by chromatography on hydroxyapatite, and this activity was further purified and assigned to endopeptidase-24.15 (EC 3.4.24.15). SDS/PAGE of both preparations of neurotensin endopeptidase revealed a major band of apparent Mr 75000, and treatment of the membrane-associated form with N-Glycanase gave no evidence that the enzyme was a glycoprotein. The membrane-associated and cytosol forms of NT endopeptidase activities, monitored for both NT-(1-10) and NT-(1-8) products, were compared in their responses to 1,10-phenanthroline, EDTA, dithiothreitol (DTT) and some synthetic site-directed inhibitors of endopeptidase-24.15 or peptidyl dipeptidase A. The effects revealed no significant differences between the two preparations, nor did the reagents discriminate between the activities generating the two NT fragments. The partially purified form of endopeptidase-24.15 was also included in this comparison: while some responses were similar, this peptidase was distinguishable in its activation by DTT and its relative resistance to inhibition by EDTA. Both forms of NT endopeptidase were found to hydrolyse other substrates, including Boc-Phe-Ala-Ala-Phe-4-aminobenzoate, bradykinin and substance P (these at faster rates than neurotensin), as well as dynorphin A-(1 8) and luliberin. The bonds hydrolysed in these neuropeptides, as well as in angiotensins I and II and alpha-neoendorphin, were defined. These studies confirm that NT endopeptidase is distinct from endopeptidase-24.15. They further show that the former is a soluble enzyme, not an integral membrane protein, that it is not peptide-specific and that it might be more appropriately named. enzyme, not an integral membrane protein, that it is not peptide-specific and PMID- 1905922 TI - Anti-insulin effects of amylin and calcitonin-gene-related peptide on hepatic glycogen metabolism. AB - To evaluate the effects of amylin and calcitonin-gene-related peptide (CGRP) as anti-insulin agents in hepatic tissue, we have studied whether these two agents counteracted the action of insulin on glycogen metabolism in isolated rat hepatocytes. In this system insulin stimulates [14C]glucose incorporation into glycogen and activates glycogen synthase. Incubation of the cells with insulin in the presence of amylin or CGRP markedly blocked the insulin stimulation of these two parameters, whereas amylin or CGRP acting alone did not induce any effect. We also examined the ability of amylin and CGRP to modify the anti-glucagon effects of insulin. In the presence of 100 nM-amylin or -CGRP, 10 nM-insulin was almost unable to counteract the inactivation of glycogen synthase and the activation of phosphorylase induced by glucagon. In contrast, neither amylin nor CGRP modified the effect of glucagon on these two enzymes. Our results indicate that amylin and CGRP are able to impair the action of insulin on hepatic glycogen metabolism. PMID- 1905923 TI - Evidence for regulation of human platelet adenylate cyclase by phosphorylation. Inhibition by ATP and guanosine 5'-[beta-thio]diphosphate occur by distinct mechanisms. AB - 1. Incubation of human platelet membranes with guanosine 5'-[beta gamma imido]triphosphate (p[NH]ppG) causes a time-dependent increase in the activation of adenylate cyclase due to Gs (the stimulatory GTP-binding protein). Forskolin enhances adenylate cyclase activity but does not interfere with the process of activation. The activation follows first-order kinetics in both the presence and the absence of the assay components. 2. ATP in the presence or the absence of an ATP-regenerating system of phosphocreatine and creatine kinase inhibits activation. 3. Hydrolysis of ATP to ADP does not lead to receptor-mediated inhibition of adenylate cyclase acting via Gi (the inhibitory GTP-binding protein). The ADP analogue adenosine 5'-[beta-thio]diphosphate (ADP[S]) does not inhibit the activation process. 4. Phosphocreatine alone inhibits adenylate cyclase activation at concentrations above 1 mM. 5. Inhibition by phosphocreatine is not due to the chelation of free Mg2+ ions. 6. Inhibition by ATP and the other assay components occurs throughout the activation process, decreasing both the rate of activation and the maximum activity obtained. 7. Maximal activation of adenylate cyclase after prolonged incubation with p[NH]ppG slowly reverses in the presence of the assay components. 8. A 10-fold excess of the GDP analogue guanosine 5'-[beta-thio]diphosphate (GDP[S]) over p[NH]ppG inhibits the activation process completely, at all stages of the time course. 9. Preincubations in the presence and absence of ATP, cyclic AMP, phosphocreatine and creatine kinase show equal sensitivity to increasing GDP[S] concentration. These data show that the inhibition observed in the presence of ATP is not due to endogenous or contaminating guanine nucleotides, and suggest that phosphoryl transfer may regulate adenylate cyclase activity. PMID- 1905924 TI - Characterization of phospholipase A2 in monocytic cell lines. Functional and biochemical aspects of membrane association. AB - Phospholipase A2 activity was characterized in the human monocytic tumour-cell lines U937 and THP1. The enzyme showed an alkaline pH optimum and substrate specificity for arachidonoyl-phosphatidylcholine. The activation of phospholipase A2 required bivalent cations (Ca2+ greater than Mg2+ = Sr2+ greater than Ba2+). Investigation of the subcellular distribution of the enzyme revealed that the phospholipase A2 activity was shifted to the cytosol in the presence of EDTA, indicating that the association of the enzyme with the cellular membranes is Ca2+ (bivalent-cation)-dependent. Stimulation of THP1 cells for 2-4 h with the phorbol ester phorbol 12-myristate 13-acetate (PMA) activated cytosolic and membrane bound phospholipase A2. At this time, no effect of PMA on phospholipase A2 activity was observed in the less mature U937 cells. However, when both cell lines were induced to differentiate along the monocytic pathway by a 2-3-day treatment with PMA, the cells released significant amounts of arachidonic acid and prostanoids. Compared with undifferentiated control cells, these PMA differentiated cells showed a decrease in cytosolic phospholipase A2 activity and an increase in membrane-bound activity. Membrane-bound and cytosolic enzyme showed the same pH optimum, Ca(2+)-dependency and substrate specificity. These data indicate that membrane-bound and cytosolic phospholipase A2 activities represent one enzyme and that the membrane-bound form is the biologically active phospholipase A2. PMID- 1905925 TI - Structural requirements of position A alpha-157 in fibrinogen for the fibrin induced rate enhancement of the activation of plasminogen by tissue-type plasminogen activator. AB - The sequence fibrinogen-A alpha-(148-160) can mimic part of the fibrin-induced rate enhancement of the activation of plasminogen by tissue-type plasminogen activator. Previously we have reported that the lysine residue at position A alpha-157 is crucial. During our further investigations on A alpha-157 we found that lysine at position A alpha-157 may be replaced by glutamic acid. This unexpected finding prompted us to re-investigate the requirements of this position. We prepared analogues of A alpha-(148-160) in which the lysine residue at position A alpha-157 was replaced by lysine derivatives (acetyl-lysine, benzyloxycarbonyl-lysine and methanesulphonylethyloxycarbonyl-lysine), acidic residues (aspartic acid and glutamic acid), basic residues (arginine and ornithine), polar residues (glutamine and methanesulphonylethyloxycarbonylornithine), apolar residues (alanine, valine, norleucine and glutamic acid 4-nitrobenzyl ester) and glycine. These analogues were tested for their stimulatory activity. When aspartic acid, glutamic acid 4 nitrobenzyl ester or norleucine is present at position A alpha-157 in A alpha (148-160) virtually all stimulatory capacity is lost. With valine at position A alpha-157 the stimulatory activity is marginal. None of the other replacements at position A alpha-157 caused loss of rate-enhancing properties. From these results we conclude that for the rate-enhancing effect of A alpha-(148-160) the side chain of the amino acid residue at position A alpha-157 must fulfill certain requirements: there must be one (as in alanine) or no (as in glycine) carbon atom in the side chain, or at least two carbon atoms and a polar group (charged or uncharged) to which a rather bulky group (such as the benzyloxycarbonyl group) or a polar group (such as the methanesulphonylethyloxycarbonyl group) may be attached. The highest activity [even higher than native A alpha-(148-160)] was obtained with ornithine, methanesulphonylethyloxycarbonylornithine or methanesulphonylethyloxycarbonyl-lysine at position A alpha-157. PMID- 1905926 TI - Synthesis of divinyl protochlorophyllide. Enzymological properties of the Mg protoporphyrin IX monomethyl ester oxidative cyclase system. AB - The resolution and reconstitution of the Mg-protoporphyrin IX monomethyl ester oxidative cyclase system into a supernatant and a pellet fraction was accomplished by a procedure involving salt treatment followed by osmotic shock. Recombination of pellet and supernatant fractions was required for cyclase activity. This restoration effect could be demonstrated using either Mg protoporphyrin IX or Mg-protoporphyrin IX monomethyl ester as the cyclase substrate in the presence or absence of S-adenosylmethionine. Pretreatment of the pellet fraction with either 8-hydroxyquinoline or desferal mesylate inhibited cyclase activity, indicating that there is a heavy-metal-ion requirement in this fraction. The cyclase supernatant protein(s) was not internalized by Sephadex G 50 and did not bind to Blue Sepharose, suggesting that it has a molecular mass of over 30 kDa and that it does not bind the cofactor NADPH. The cyclase supernatant protein did bind to MgProtoMe2-bound Sepharose and could be eluted by raising the pH to 9.7 in the presence of 4 mM-n-octyl glucoside. The pH optimum of the cyclase was 9.0. About a 40-fold purification of the cyclase supernatant protein was achieved by a combination of (NH4)2SO4 fractionation and phenyl-Sepharose chromatography. PMID- 1905927 TI - Further studies on the localization of the reactive lysyl residue of pyruvate carboxylase. AB - We have shown the increase in the acetyl-CoA-independent activity of sheep liver pyruvate carboxylase following trinitrophenylation of a specific lysine residue (designated Lys-A) to be the result of a large stimulation of the first partial reaction and a slight stimulation of the second partial reaction catalysed by this enzyme. Like acetyl-CoA, the activators adenosine 3',5'-bisphosphate and CoA did not stimulate the catalytic activity of the trinitrophenylated enzyme in either the overall reaction or the first partial reaction. Conversely, trinitrophenylation had no effect on activation of the overall reaction and the second partial reaction by acetyl-phosphopantetheine. Protection experiments demonstrated that the presence of both acetyl-CoA and adenosine 3',5' bisphosphate decreased the rate of loss of activity during exposure of sheep liver pyruvate carboxylase to trinitrobenzenesulphonic acid (TNBS), whereas acetyl-phosphopantetheine did not. 5'-AMP and acetyl-dephospho-CoA did not protect the enzyme against loss of activity, whereas the presence of adenosine 2',5'-bisphosphate only slightly decreased the rate of modification. This suggests that Lys-A interacts with the adenosine nucleotide portion of the acetyl CoA molecule, specifically the 3'-phosphate moiety. Acetyl-CoA and adenosine 3',5'-bisphosphate were shown to protect pyruvate carboxylase from Saccharomyces cerevisiae against inhibition by TNBS. A [14C]acetyl-CoA-binding assay demonstrated that modification of Lys-A inhibits the binding of acetyl-CoA to S. cerevisiae pyruvate carboxylase, indicating that Lys-A is at or near the acetyl CoA-binding site. PMID- 1905928 TI - Site specificity in the interactions of synapsin 1 with tubulin. AB - Synapsin 1 is one of a family of phosphoproteins located on small synaptic vesicles (SSV) in the presynaptic terminal, and probably plays a critical role in the process of neuronal exocytosis by providing regulated linkages between SSV and the cytoskeleton. Two forms of synapsin 1 are produced from a single gene by differential mRNA splicing: 1a, 706 amino acid residues, and 1b, 670 residues. Synapsin 1 has two structural domains, a globular N-terminal head domain and an elongated tail domain. Electron microscopy of nerve terminals in situ and reconstitution studies in vitro indicates that synapsin 1 can interact with microtubules, microfilaments and brain spectrin. In vitro, synapsin 1 can bundle microtubules. This could either occur by synapsin 1 being at least bivalent for microtubules, or by univalent synapsin 1 molecules aggregating to form complexes that are more than univalent. To resolve this question, we have taken the approach of preparing defined fragments of synapsin 1 from each structural domain and analysing them for tubulin-binding activity. Our results show that there are tubulin-binding sites in both head and tail domains. We conclude that synapsin 1 monomers should be able to cross-link microtubules. PMID- 1905929 TI - Irreversible inactivation of beta-lactamase I from Bacillus cereus by chlorinated 6-spiroepoxypenicillins. AB - On incubation of the chlorinated 6-spiroepoxypenicillin anilides (I) and (II) [formula: see text] with beta-lactamase 1 from Bacillus cereus, three distinct processes are observed. The inhibitors act as (a) substrates, the turnover of which respectively results in a single product, namely 6-substituted 2(H)-3,4 dihydro-1,4-thiazine, (b) a transiently inhibited enzyme complex, and finally (c) an irreversibly inactivated enzyme complex. Although differing only in their stereochemistry at one centre, the anilide (K) is a more potent irreversible inactivator of beta-lactamase I than is compound (II). Analysis of irreversibly inactivated beta-lactamase I by isoelectric focusing and inspection of peptide fragmentation maps indicated that irreversible inactivation appears to be accompanied by covalent modification. These studies reveal that the chlorinated 6 spiroepoxypenicillin anilide (I) is a mechanism-based beta-lactamase inhibitor. PMID- 1905930 TI - Purification and N-terminal sequence of the p21rho GTPase-activating protein, rho GAP. AB - Eukaryotic cells contain numerous small-molecular-mass GTP-binding proteins, but the processes that they regulate are not known. Different members of this protein family appear to be associated with specific GTPase-activating proteins (GAPs), and we have previously reported the identification of a cytoplasmic GAP (rho GAP) that stimulates the GTPase activity of p21rho but not of other small-molecular mass GTP-binding proteins. We have now purified rho GAP 2000-fold from human spleen tissue using f.p.l.c. Electrotransfer of this 27.5 kDa protein on to an Immobilon-P transfer membrane followed by reconstitution of its enzymic activity confirmed its identity. Rho GAP was subjected to N-terminal sequence analysis and 15 amino acids were obtained. The sequence showed 53% identity with a region present in IRA1, a protein which stimulates the GTPase activity of RAS proteins in Saccharomyces cerevisiae. These results suggest that there is a family of sequence-related GAP proteins, which to date includes ras GAP and its yeast counterparts IRA1 and IRA2, rho GAP and the Neurofibromatosis gene product NF1. PMID- 1905931 TI - Human aortic proteoglycans of subjects from districts of high and low prevalence of atherosclerosis in China. AB - The contents of three species of proteoglycans (PGs), heparan sulfate PG(HSPG), chondroitin sulfate PG(CSPG) and dermatan sulfate chondroitin sulfate PG(DSCSPG), in human thoracic aortas of subjects from districts of high (Beijin, in North China) and low (Nanning, in South China) prevalence of atherosclerosis in China were quantitated. Higher aortic HSPG and DSCSPG (but lower DS) in samples from Nanning than those from Beijing might be implicated in the lower prevalence of atherosclerosis in the former. PMID- 1905932 TI - [Response of respiratory exchange ratio (R) to sinusoidal work load in humans]. AB - An examination was made of the response of respiratory exchange ratio (R), carbon dioxide output (VCO2) and oxygen uptake (VO2) to sinusoidal work load with periods (T) of 1-16 min in six healthy men to determine whether R response is sinusoidal. The influence of the ratio of the amplitude of VCO2 to that of VO2 and the phase lag between them on R response was also studied by computer simulation. The results and conclusions obtained are as follows: 1) With decrease in the period, the amplitudes of VO2 and VCO2 dropped exponentially, becoming least at T of 1 min (T = 1 min). In contrast, the amplitude of R was largest at T = 4 min and subsequently decreased progressively. 2) The peak amplitude of R at T = 4 min can be explained by the larger phase lag and relatively low of amplitude of VCO2 to VO2. 3) The smallest amplitude of R at T = 1 min was due not to the ratio of amplitude or phase lag, but to remarkably smaller amplitudes of VO2 and VCO2. 4) The phase lag of VO2 to sinusoidal work load was smaller than that of VCO2. Phase lag of R was considerably larger than that of VO2 or VCO2. 5) The response curve of VO2 and VCO2 is a sinusoidal curve with the same period as exercise. However, the response of R is not a real sinusoidal but a deformed biphasic curve with a high crest and low trough. The deformity is determined by the phase lag between VO2 and VCO2 response and also the ratio of amplitude of VCO2 to that of VO2. PMID- 1905933 TI - Synthetic peptides corresponding to sequences in HIV envelope gp41 and gp120 enhance in vitro production of interleukin-1 and tumor necrosis factor but depress production of interferon-alpha, interferon-gamma and interleukin-2. AB - Patients with human immunodeficiency virus (HIV) infections have aberrant production of a number of lymphokines and monokines. Envelope glycoproteins are believed to be important in HIV pathogenesis and may influence the production of these cytokines. Therefore, synthetic peptides corresponding to amino acid sequences 735-752 and 846-860 of glycoprotein gp41 and to amino acid sequence 304 328 of gp120 were investigated for their abilities to affect the production of the following cytokines by normal peripheral blood mononuclear cells in the presence of appropriate inducers: interferon (IFN)-alpha, IFN-gamma, interleukin (IL)-1, IL-2, and tumor necrosis factor (TNF). In contrast to cells and inducers alone (or in the presence of a control peptide), gp41 or gp120 synthetic peptides were able to depress the production of IFN-alpha, IFN-gamma and IL-2. In contrast, these peptides produced an elevation of the production of IL-1 and TNF. The effect of the gp41 peptides was more marked than that of gp120 peptides in most cases. These studies indicate that these HIV envelope glycoproteins may be directly responsible for aberrant lymphokine and monokine production in patients infected with this virus and therefore may be at least partially responsible for the pathogenesis of AIDS. PMID- 1905934 TI - Stimulation of adherent cells by addition of purified proteins of viral hemorrhagic septicemia virus to trout kidney cell cultures. AB - Purified proteins of the virus causing viral hemorrhagic septicemia in the trout were added to cultures on semisolid medium of leukocytes obtained from either healthy or immunized rainbow trout. Adherent cells were specifically stimulated by the glycoprotein of the viral spikes and, to a lesser extent, by the nucleoproteins. In contrast, a specific memory response was associated more with the nucleoproteins than with the glycoprotein when leukocytes from trout immunized with the virus were employed. These results suggest the necessity of employing both proteins in subunit vaccination trials and the possibility of using this assay to select the proper epitopes for genetically engineered proteins during subunit vaccine development. PMID- 1905935 TI - Infection of SCID mice with lactate dehydrogenase-elevating virus stimulates B cell activation. AB - Mice of the C.B-17 strain homozygous for the scid mutation (SCID mice) were infected with lactate dehydrogenase-elevating virus (LDV), and plasma samples obtained at intervals up to 42 days postinfection were analyzed for total immunoglobulins, anti-LDV antibodies, virus-specific immune complexes, and viremia levels. The mice responded to LDV infection with transient increases in total blood IgM, production of IgM-antigen complexes and IgM anti-LDV, as well as increased blood IgG2a. However, SCID mice failed to make a specific IgG2a anti LDV immune response, and their blood LDV levels were elevated about 100-fold relative to those of control mice. The results suggest a role for IgG antibodies in the regulation of viremia and demonstrate a viral pathway of B-cell differentiation in SCID mice. PMID- 1905936 TI - Predominant abnormality in cerebral glucose utilization in late-onset dementia of the Alzheimer type: a cross-sectional comparison against advanced late-onset and incipient early-onset cases. AB - Global cerebral blood flow and the cerebral metabolic rates of oxygen, CO2, glucose and lactate were studied in 11 patients aged 61-78 years who had been clinically diagnosed as suffering from incipient late-onset dementia of the Alzheimer type (DAT), and in 7 patients aged 66-83 years, in whom advanced late onset DAT had been diagnosed, using the Kety-Schmidt technique. In incipient late onset DAT, the predominant abnormality was a 45% reduction in cerebral glucose utilization, whereas cerebral blood flow and the cerebral metabolic rate of oxygen were diminished by only 17% and 18%, respectively. A severe imbalance between oxygen utilization and glucose utilization thus became obvious. In contrast, in advanced stages of late-onset DAT, this imbalance between oxygen and glucose utilization rates in the brain became smaller and smaller, and cerebral blood flow diminished markedly; these biological brain parameters finally all settled down at between 55% and 65% of the corresponding control values. The predominant abnormality in brain glucose utilization in incipient late-onset DAT may be associated with an impairment of its control mechanism(s), which are assumed to be either an influence of brain insulin action, or brain insulin receptor function, or both. PMID- 1905937 TI - Treatment with antioxidants does not prevent loss of dopamine in the striatum of MPTP-treated common marmosets: preliminary observations. AB - Administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to common marmosets causes a profound loss of dopamine and serotonin in the striatum. Additional daily systemic treatment of monkeys with the antioxidants ascorbic acid (100 mg/kg) and alpha-tocopherol (2,350 mg/kg) prior to, during and following administration of MPTP does not prevent the loss of dopamine and serotonin in the striatum, suggesting that these antioxidants are unable to protect dopaminergic neurones against neurotoxicity of MPTP. PMID- 1905939 TI - Instantaneous gene transfer from donor to recipient microorganisms via electroporation. AB - Simplified electroporation methodologies have been developed that reliably yield transformants with only minutes of effort. Neither DNA purification, cells in specific phase of growth, cell washing nor chilled cuvettes are required to obtain transformants. Electroporation can be used to transfer plasmid or chromosomal DNA directly from donor to recipient cells. This simplified direct method of electroporation has been demonstrated to work for both intra- as well as interspecies transformations using a variety of microorganisms. The use of electroporation to purify plasmid DNA was also investigated and found to be inferior to conventional plasmid isolation procedures. PMID- 1905938 TI - Risk-benefit assessment of drugs used for the treatment of menstrual disorders. AB - This article considers the benign yet debilitating conditions of menorrhagia, dysmenorrhoea and irregular menstrual bleeding. Surprisingly little has been reported in the literature concerning these common ailments which can detract from the quality of female life during the reproduction years. Both dysmenorrhoea and menorrhagia are subjective complaints, but despite accurate means of measuring menstrual blood loss such quantification is rarely performed. This lack of diagnostic accuracy is a cause for concern, especially as both medical and surgical treatment are not without risk. The therapeutic alternatives which are commonly prescribed in an attempt to rectify such menstrual disorders are discussed. These include the nonsteroidal anti-inflammatory agents, the combined oral contraceptives, danazol, progestogens, antifibrinolytics, haemostatics, luteinising hormone releasing hormone analogues and clomiphene. The results of clinical trials which have utilised these various agents are considered in terms of both the effectiveness of treatment and its potential adverse effects. PMID- 1905940 TI - [Multiple nerve root tumors and neurofibromatosis: contribution of magnetic resonance imaging]. AB - Three patients (two females and one male) with radiculospinal neurologic involvement secondary to different forms of neurofibromatosis are reported. The first two met the diagnostic criteria for NF-1, although case 2 had a posterior fossa meningioma, which is an uncommon finding in this group. The male patient had an apparently sporadic NF-2, with bilateral acoustic nerve neurinoma, multiple meningioma, multiple radicular neurinoma and an intraspinal tumor apparent in magnetic resonance imaging. In the three cases the whole central nervous system was evaluated with gadolinium-enhanced magnetic resonance imaging. A great number of radicular tumors, many of which were asymptomatic, were detected. In spite of the severity of the clinical features, the three patients showed a dramatic improvement after the surgical removal of the symptomatic tumors. The use of magnetic resonance is encouraged, owing to its high resolution and safety, for the assessment of incidence, character and localization of tumors in neurofibromatosis and to establish a good clinico-lesional correlation before surgery. This technique may help to a better understanding of the spectrum of abnormalities in each type of neurofibromatosis, thus facilitating the evaluation of this complex condition. PMID- 1905941 TI - Genomic Southern analysis with alkaline-phosphatase-conjugated oligonucleotide probes and the chemiluminescent substrate AMPPD. AB - We have used a chemiluminescent detection method to improve both the sensitivity and the speed of detection of human genes with oligonucleotide probes. A direct chemiluminescent substrate (AMPPD) was used in combination with an alkaline phosphatase-labeled oligonucleotide probe to detect the human tissue of plasminogen activator gene by Southern blot analysis. X-ray exposures obtained after 4 h were comparable to those obtained after 7 days with a 32P-labeled oligomer. After 16 h, the signal was 12 times greater than the 32P signal. The detection of the single-copy tissue plasminogen activator gene in 0.25 micrograms of human genomic DNA (76,000 molecules) was achieved. The improved sensitivity obtained by chemiluminescent detection should increase the usefulness of oligonucleotide probes in the direct Southern analysis of human genetic disorders. PMID- 1905942 TI - Effects of ethane-1-hydroxy-1, 1-diphosphonate on cell differentiation, and proteoglycan and calcium metabolism, in the proximal tibia of young rats. AB - The effects of ethane-1-hydroxy-1, 1-diphosphonate(EHDP) on cell differentiation, and on the metabolism of proteoglycan and calcium in the epiphyseal plate and metaphysis of rats were investigated through histology and autoradiograms of [35S]-sulfate, 45Ca, and [3H]-thymidine. Suppression of bone resorption in the metaphysis due to low dose EHDP administration was associated with a proliferation of osteoclasts with an increased number of nuclei. High dose EHDP induced enlargement of the hypertrophic zone of the epiphyseal plate and suppression of calcification of the cartilage matrix. This change had a significant association not only with the suppression of chondroitin sulfate synthesis and the degradation in the cartilage matrix, but also with the suppression of growth and differentiation of chondrocytes. Calcification was also inhibited in the metaphysis, and growth and differentiation from undifferentiated mesenchymal cells to osteoblasts, osteocytes, and osteoclasts were also suppressed by high dose EHDP. PMID- 1905943 TI - [The early diagnosis of intestinal ischemia by gammagraphic study]. AB - Intestinal wall necrosis without perforation was produced in six dogs. Another group of three dogs served as a control. The histologic findings, the degree of ischemia and scintigraphic images obtained after the infusions of autologous white blood cells labelled with indium-111 oxine were correlated. Positive scans were obtained in all the dogs with proven intestinal ischemia. Negative scans appeared in the dogs without ischemic insult and a false-positive scan were observed in a control dog with diarrhea. PMID- 1905944 TI - Health care economics and policy. AB - It is difficult to objectively and comprehensively measure the effects of the rheumatic diseases or their treatment. The concept of patient outcome measurement now encompasses many components: physical health, mental health, everyday functioning, general perceptions of well-being, treatment side effects, and cost versus-benefit. Accordingly, a major research effort has been directed toward developing methods for the measurement of health status and patient outcome in arthritis and other rheumatologic diseases. The intent of this effort is to produce standard measures for evaluating disease impact, treatment impact, and costs of care. Numerous questionnaire-based instruments have appeared for clinical researchers to use, but they are couched in unfamiliar jargon and use terms such as "indirect costs," "lost productivity," and "quality-of-life." As these articles appear in the literature and clinical investigators include such measures in their studies or clinical trials, a review of the terms and an evaluation of these measures appears timely. This report describes the present state of the art, emerging problems, and future directions. PMID- 1905945 TI - Acute aortic occlusion secondary to Aspergillus endocarditis in an intravenous drug abuser. AB - A 55-year-old black man, an intravenous substance abuser who had an acute arterial embolus to the distal aorta originating from his mitral valve, was noted on pathologic examination of the clot to have aspergillosis emboli. The infective endocarditis also resulted in emboli to the brain with subsequent death. PMID- 1905946 TI - Determination of released CD4 and CD8 antigens in the suction-blister fluid and horny-tissue extract in patients with psoriasis. AB - The amounts of soluble CD4 and CD8 antigens were measured in suction-blister fluid and extracts of horny tissue in patients with psoriasis. The levels of soluble CD4 and CD8 in the suction-blister fluid of lesional skin in psoriasis was significantly higher than from normal skin and the uninvolved skin in psoriasis. Levels of soluble CD4 and CD8 in the extracts of horny tissue in psoriasis were significantly higher than those from non-psoriatic skin. PMID- 1905947 TI - Anti-H IgM (kappa) autoantibody mediated severe intravascular haemolysis associated with malignant lymphoma. PMID- 1905948 TI - Molecular and endocrine characterization of a mutation involving a recombination between the steroid 21-hydroxylase functional gene and pseudogene. AB - The gene encoding steroid 21-hydroxylase activity, P450c21B, is located in the major histocompatibility complex (MHC) class III region, in close proximity to a highly homologous pseudogene, P450c21A. Recombinations between P450c21B and P450c21A have been shown to result in deficiency of 21-hydroxylase activity, the usual cause of congenital adrenal hyperplasia (CAH). A mutant P450c21 gene from a patient with simple virilizing CAH was identified and shown to be consistent with a recombination between P450c21A and P450c21B. Sequence analysis of the mutant gene showed the recombination site to be located between the first exon and the second intron. The mutant gene encodes a leucine instead of the normal proline at codon 31. This mutation resides on a chromosome bearing the HLA-B44 serotype. A comparison of mutations associated with HLA-B44 and that normally found with the HLA-Bw47 serotype suggests that the HLA-B44 mutations are of more ancient origin. The patient's homologous chromosome has a deletion of P450c21B. Endocrinological testing therefore allows for testing of the mutant gene in genetic isolation. Such testing demonstrated that the patient was capable of producing aldosterone and retaining sodium in response to a low-sodium diet, indicating that the mutant gene encodes an enzyme with partial 21-hydroxylase activity. PMID- 1905949 TI - Intrasubject variability in the pharmacokinetics of ethynyloestradiol. AB - Intrasubject and intersubject variability in the metabolism of ethynyloestradiol (EE) was assessed in a cross-over randomized study of 6 women who each received 3 months treatment with 50 micrograms EE and 50 micrograms EE with 250 micrograms levonorgestrel (LNG). Blood samples were collected at the end of each treatment month, assayed for EE and the half-life of elimination (Tel) and bioavailability (area under the serum concentration-time curve, AUC) calculated. Intrasubject variability for Tel and AUC varied markedly; the variability was random and not correlated with the formulation administered. The intrasubject variability for Tel and AUC was 31 and 17%, respectively, and intersubject variability 66 and 95%. The intersubject range of values was more than 3-fold for both Tel and AUC and the intrasubject range about 2-fold. The pharmacokinetics of EE were not influenced by LNG; mean values for Tel and AUC were 17.3 +/- 5.5 h and 11.1 +/- 3.8 ng/ml/h, respectively, when EE was administered alone compared with 16.4 +/- 4.8 h and 12.5 +/- 3.9 ng/ml/h when given with LNG. However, EE influenced the metabolism of LNG; Tel for LNG was 19.3 +/- 4.2 h when administered alone and significantly higher (30.0 +/- 11.2 h) when given with EE. There was no correlation between the rate of metabolism of EE and that of LNG. The intrasubject variability shown in this and other studies suggests that genetic factors are less important in intersubject variability than previously thought. Some implications of intrasubject variability are discussed. PMID- 1905950 TI - Detection of interferon-gamma mRNA in psoriatic epidermis by polymerase chain reaction. AB - Psoriatic skin lesions contain HLA-DR positive T lymphocytes, and other activation antigens, which suggest that the T cells may be producing lymphokines. Gamma interferon is produced by activated T cells, and its presence in psoriasis has been inferred by the lesional keratinocyte expression of 3 gamma interferon inducible proteins i.e. HLA-DR, intercellular adhesion molecule-1, and gamma-IP 10. To determine whether gamma interferon is being produced directly in psoriatic lesions, punch biopsies of normal and diseased skin were separated into epidermal sheets and dermal fragments. Total cellular RNA was isolated from each epidermal and dermal compartment, and reverse transcribed followed by amplification of the resultant DNA by polymerase chain reaction. The amplification process involved the use of 5' and 3' primers for gamma interferon, and tumor necrosis factor alpha, with beta-actin serving as a control. Gamma interferon mRNA, but not tumor necrosis factor alpha mRNA, was detectable in 4 of 5 psoriatic epidermal specimens. Neither mRNA was detectable in any normal skin dermal/epidermal specimens. Gamma interferon mRNA was also detectable in a single psoriatic dermal specimen. If reverse transcriptase was omitted, no polymerase chain reaction products were detected, indicating that the fragments detected were not derived from contaminating genomic DNA. These results indicate that gamma interferon mRNA can be extracted and successfully detected from human psoriatic lesional skin biopsies, using polymerase chain reaction technology. This molecular approach can easily be expanded to measure many other cytokines in both epidermal and dermal locations. The detection of gamma interferon in this clinical setting may be of particular pathophysiological significance because injection of gamma interferon has been reported to induce psoriatic lesions. PMID- 1905951 TI - Transforming potential is detectable in arteriosclerotic plaques of young animals. AB - The carcinogen-treated cockerel is a model for studying the early stages of arteriosclerotic plaque development. Carcinogen administration accelerates arteriosclerotic plaque development in cockerels, and transforming elements are present in DNA from advanced human plaques. In this study, we asked whether transforming elements could also be detected at early stages of plaque development in cockerels. NIH3T3 cells were transfected with DNA from plaques isolated from carcinogen-treated cockerels and from the healthy arterial wall underlying the plaques. Approximately 5 x 10(6) cells from each group were injected into nude mice. Tumors appeared in five of five mice in the plaque DNA group; no tumors appeared in mice from the healthy arterial wall group. All five plaque DNA-associated tumors hybridized to a cockerel genomic probe. Eight cockerel-specific bands were identified in EcoRI digests of first-round (primary) tumors. DNA from a primary tumor was tested in a second round of transfection. Five of five mice developed tumors after injection with these secondary transformants. All second-round tumors contained cockerel DNA, and a prominent cockerel-specific band (greater than 28 kb) was seen in EcoRI digests of all second-round tumors. In addition, a 5.2-kb band appeared prominently in one of five second-round tumors. No evidence was found for activation of the oncogenes Ha-ras, Ki-ras, src, or myc in the plaque-associated tumors. Similarly, DNA from plaque-associated tumors did not hybridize to probes for Marek disease virus, herpes simplex virus 1, or reverse transcriptase, suggesting that neither herpesviruses nor retroviruses are involved in the transforming activity of plaque DNA. These results indicate that transforming elements are a general property of arteriosclerotic plaques and are detectable in plaques of young animals. PMID- 1905952 TI - Activation of calpain I and hydrolysis of calpain substrates (actin-binding protein, glycoprotein Ib, and talin) are not a function of thrombin-induced platelet aggregation. AB - Calcium-activated neutral proteinase (calpain) has been shown to cleave proteins involved in the maintenance of cell structure. In human platelets, substrates of calpain include glycoprotein Ib (GPIb), actin-binding protein (ABP), and talin. GPIb-ABP complexes can be isolated in detergent extracts and are thought to represent membrane-cytoskeleton attachment sites. It has been hypothesized that the hydrolysis of GPIb-ABP by calpain is regulated by the extent of binding of this proteinase to the plasma membrane-cytoskeleton interface with platelet activation. Recently, another calpain substrate (talin) has been shown to redistribute from the cytoplasm to the plasma membrane-cytoskeleton interface as the result of thrombin stimulation. To investigate the intracellular distribution of calpain I, we employed the monoclonal antibody B27D8, specific for the heavy chain (catalytic subunit) of calpain I. Indirect immunofluorescent staining of resting human platelets revealed undetectable surface antigen. Permeabilization with Triton X-100, however, revealed a diffuse intracellular antigen consistent with a cytosolic distribution. To determine whether this antigen distribution reflected the proenzyme or the activated form of calpain I and to assess the degree of hydrolysis of ABP, GPIb, and talin, we employed B27D8 and murine monoclonal antibodies against ABP (1B3 and 3D1), GPIb (LJIb10), and rabbit polyclonal antibodies against talin (A2 and B11) in a quantitative immunotransblot assay. Examination of resting platelets revealed that calpain I existed as the 85-kd proenzyme form and that ABP, GPIb, and talin existed in their native intact forms. When platelets were aggregated with thrombin, autoproteolysis of calpain I occurred within the 30 seconds required to completely solubilize platelet aggregates in sodium dodecyl sulfate-containing buffer and not as a direct result of thrombin-induced activation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1905953 TI - Role of the hexapeptide disulfide loop present in the gamma-carboxyglutamic acid domain of human protein C in its activation properties and in the in vitro anticoagulant activity of activated protein C. AB - In order to examine whether the structural integrity of the hexapeptide disulfide loop (residues 17-22), present in the gamma-carboxyglutamic acid (gamma) domain of human protein C (PC), and common to all vitamin K dependent coagulation proteins, is necessary for its anticoagulant properties, we employed recombinant (r) DNA technology to generate two important variants that would address this issue. One such mutein contained aspartic acid for gamma-residue substitutions at sequence positions 19 and 20 ([gamma 19D, gamma 20D]r-PC) in the light chain of the mature protein, and the other possessed a serine for cysteine substitution at position 22 ([C22S]r-PC of the same light chain. A subpopulation of molecules of these mutant proteins, containing the maximum levels of gamma-residues in each, has been purified by fast-protein anion-exchange liquid chromatography and affinity chromatography on an anti-human PC column. A study of the kinetic characteristics of the inhibition by Ca2+ of the thrombin-catalyzed activation rates of these variants, and the corresponding stimulation by Ca2+ of the thrombin/thrombomodulin-catalyzed activation rates of the same recombinant PC molecules, demonstrated that higher concentrations of Ca2+ were required to display these effects, when compared to wild-type (wt) r-PC and human plasma PC. This suggested that the kinetically relevant Ca2+ site responsible for these effects on activation of PC, and known to be present in another domain of PC, was affected by both mutations in the gamma-domain. The recombinant PC variants were converted to their activated forms ([gamma 19D, gamma 20D]r-APC and [C22S]r-APC) and assayed for their Ca(2+)-dependent anticoagulant activities.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1905954 TI - Mechanistic coupling of transport and phosphorylation activity by enzyme IImtl of the Escherichia coli phosphoenolpyruvate-dependent phosphotransferase system. AB - Mannitol bound to enzyme IImtl could be trapped specifically by rapid phosphorylation with P-HPr. The assay was used to demonstrate transport of mannitol across the cytoplasmic membrane with and without phosphorylation of mannitol. The latter was 2-3 orders of magnitude slower. The fraction of bound mannitol molecules that was actually phosphorylated, the efficiency of the trap, was less than 50%. The efficiency was not very different for enzyme IImtl embedded in the membrane of vesicles with an inside-out orientation or solubilized in detergent. Subsequently, it is argued that the fraction of the bound mannitol molecules that was not phosphorylated dissociated into the cytoplasmic space. A model for the catalytic mechanism of enzyme IImtl is proposed on the basis of interpretations of the present experiments. The main features of the model are the following: (i) mechanistically, the coupling between transport and phosphorylation is less than 50%; (ii) in the physiological steady state of mannitol transport and metabolism, the coupling is 100%; (iii) phosphorylated enzyme IImtl catalyzes facilitated diffusion at a high rate; (iv) the state of phosphorylation of the cytoplasmic domain modulates the activity of the translocator domain; (v) the enzyme catalyzes phosphorylation of free cytoplasmic mannitol at least as fast as it catalyzes transport plus phosphorylation of free periplasmic mannitol. PMID- 1905955 TI - Functional equivalence of metarhodopsin II and the Gt-activating form of photolyzed bovine rhodopsin. AB - Absorption of a photon by the visual pigment rhodopsin leads to the formation of an activated conformational state, denoted rho*, which is capable of activating the visual G-protein, Gt. The bleaching of rhodopsin can be resolved into a series of spectrally distinct photointermediates. Previous studies suggest that the photointermediate metarhodopsin II (meta II, lambda max of 380 nm) corresponds to the physiologically active form rho*. In the studies reported herein, spectral and enzymological data were analyzed and compared so as to evaluate the temporal correspondence between meta II and rho*. This information was obtained by direct observation of the meta II and rho* decay times in parallel experiments utilizing identical preparations of urea-stripped, bovine retinal rod outer segment disk membranes at pH 8.0, 20 degrees C. Postflash spectra were deconvolved to resolve the meta II absorbance at 380 nm, and a decay time for the loss of meta II of 8.2 min (SD = 0.5 min) was obtained from fitting these data to a single-exponential decay process. The diminishing ability of bleached rhodopsin to activate Gt was measured by monitoring the level of catalyzed exchange of Gt-bound GDP for a nonhydrolyzable GTP analogue. Analysis of the decrease in the initial velocity of nucleotide exchange, measured at various postflash incubation times, yielded a rho* decay time of 7.7 min (SD = 0.5 min) when analyzed as a single-exponential process. The similarity of these decay times provides direct evidence that meta II and rho* are present over the same time regime, and further supports the equivalence of these two forms of photoactivated rhodopsin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1905956 TI - Orientation and linear dichroism of Mastigocladus laminosus phycocyanin trimer and Nostoc sp. phycocyanin dodecamer in stretched poly(vinyl alcohol) films. AB - The linear dichroism (LD) spectra of the C-phycocyanin (C-PC) trimer disks oriented in poly(vinyl alcohol) films (PVA) at room temperature and at 95 K were determined. Utilizing the known atomic coordinates of the chromophores (Schirmer, T., Bode, W. and Huber, R. (1987) J. Mol. Biol. 196, 677-695) and theoretical estimates of the orientations of the transition dipole moments relative to the molecular framework, the LD spectra were simulated using the pairwise exciton interaction model of Sauer and Scheer (Biochim. Biophys. Acta 936 (1988) 157 170); in this model, the alpha 84 and beta 84 transition moments are coupled by an exciton mechanism, while the beta 155 chromophore remains uncoupled. Linear dichroism spectra calculated using this exciton model, as well as an uncoupled chromophore (molecular) model, were compared with experimental LD spectra. Satisfactory qualitative agreement can be obtained in both the exciton and molecular models using somewhat different relative values of the theoretically estimated magnitudes of the beta 155 oscillator strength. Because the relative contributions of each of the chromophores (and thus exciton components) to the overall absorption of the C-PC trimer are not known exactly, it is difficult to differentiate successfully between the molecular and exciton models at this time. The linear dichroism spectra of PC dodecamers derived from phycobilisomes of Nostoc sp. oriented in stretched PVA films closely resemble those of the C-PC trimers from Mastigocladus laminosus, suggesting that the phycocyanin chromophores are oriented in a similar manner in both cases, and that neither linker polypeptides nor the state of aggregation have a significant influence on these orientations and linear dichroism spectra. The LD spectra of oriented phycocyanins in stretched PVA films at low temperatures (95 K) appear to be of similar quality and magnitude as the LD spectra of single C-PC crystals (Schirmer, T. and Vincent, M.G. (1987) Biochim. Biophys. Acta 893, 379-385). PMID- 1905957 TI - Purification and characterization of the recombinant human aldose reductase expressed in baculovirus system. AB - Large quantities of recombinant human aldose reductase were produced using Spodoptera frugiperda cells and properties of the enzyme were characterized. Direct purification of the recombinant aldose reductase by affinity column chromatography using Matrex gel orange A yielded a single 36 kDa band, similar in size to the purified human muscle aldose reductase, on a sodium dodecyl sulfate polyacrylamide gel after silver staining. The isoelectric point of the recombinant enzyme was 5.85 which is identical to the human muscle aldose reductase. Following the treatment with an acylamino-acid releasing enzyme, the blocked NH2-terminal amino acid was identified to be acetylalanine. The successive NH2-terminal sequence and that of the COOH-terminal peptide concurred with the expected translated sequence. Kinetic analyses of the recombinant enzyme activity for various substrates and the cofactor, NADPH, demonstrated a good agreement with the previously reported kinetic data on the purified human aldose reductase. A high concentration of (NH4)2SO4 elicited a significant increase in both Km and Kcat for DL-glyceraldehyde as well as D-glucose. Although IC50 values for most of the aldose reductase inhibitors with recombinant enzyme were found to fall within the comparable range of those obtained with nonhuman mammalian enzymes, the IC50 value for epalrestat was more than 10-fold higher in the recombinant enzyme. These results indicate that the recombinant human aldose reductase expressed in the baculovirus system possesses structurally and enzymatically similar properties as those reported for the native human enzyme and should serve as a superior enzyme preparation to nonhuman mammalian enzymes for the screening of the efficacy and potency of newly developed aldose reductase inhibitors. PMID- 1905958 TI - Collagen in the ageing human intervertebral disc: an increase in covalently bound fluorophores and chromophores. AB - Human disc tissue gradually changes in colour from white in the young to yellow brown in the elderly. It was investigated to what degree this colouration and an associated fluorescence (which are characteristic of the non-enzymic reaction products of sugars or oxidized lipids with proteins), were the result of covalent derivatives on the collagen and other extracellular matrix proteins. Annulus fibrosus was obtained from four subjects aged 19 to 92 years. Papain-solubilized samples of tissue showed increasing yellow colour and the glycation-related fluorescence with age. On chromatography of CNBr-digests of tissue, the yellow colour and fluorescence remained bound to the CNBr-peptide fragments of the collagen and other matrix proteins. One peptide, alpha 1(II)CB12 (from type II collagen), was selected for purification and shown to contain increasing amounts of the characteristic fluorescence with age. Sequencing by Edman degradation over 24 cycles confirmed the identity of the peptide, and by analysis of a portion of the PTH-derivatives showed fluorescence at cycle 11, a lysine residue. The results imply that much of the yellow colour and characteristic fluorescence that accumulate in ageing human discs are contributed by covalent adducts (possibly derived from non-enzymic reactions with carbohydrates or lipids) linked to the collagen and probably to other long-lived matrix proteins. The disc is perhaps particularly susceptible to such protein modifications because, being large and avascular, of its tendency to a low oxygen tension. Such modifications to structural proteins may contribute to the commonly observed degeneration and impaired material function of ageing disc tissue. PMID- 1905959 TI - [Nutritional support in patients with thoracic trauma. Usefulness of an enteral diet with a high fat content]. AB - The purpose of this study is to evaluate the effects and clinical tolerance of an enteral diet containing 55% "AET" in the form of fat and only 28% in the form of H. C. in a group of 17 polytraumatized patients admitted to the Intensive Care Unit with assisted ventilation as a result of thoracic traumatism. The average age of the patients was 36.6 +/- 17 years, and they remained in Intensive Care for more than 10 days. Energetic requirements were estimated at 1,800 +/- 180 Kcal per day. Enteral intake commenced on day 4.5 +/- 1.2 and 90% of the estimated requirements was achieved at 8.5 +/- 2.9 days. Average duration of the Enteral Nutrition was 15 +/- 3.7 days, Tolerance of the diet was considered good and problems due to intolerance leading to suspension of the diet were mainly related to worsening of the clinical condition. The volumen per minute expired per Kg of weight descended gradually and assisted ventilation was removed at 16 +/- 5.4 days, 5 patients died, mainly due to septic problems. There was a significant improvement in surviving patients with regard to levels of transferrin (p less than 0.01), prealbumin (p less than 0.001) and RBP (p less than 0.05), and no improvement was observed in the patients who had died. The nitrogenated balance was positive from the ninth day onwards in surviving patients, and remained negative in the patients who had died. In conclusion, this enteral diet with a high intake of fats, showed good tolerance and is beneficial in patients with thoracic traumas which require assisted ventilation. PMID- 1905960 TI - [Comparative study of two lipid emulsions in patients receiving total parenteral nutrition]. AB - INTRODUCTION: the use of lipid emulsions together with glucose as a calorie source in parenteral nutrition has undisputed advantages. Their isotony and high calorie content mean they are essential for peripheric parenteral nutrition and in parenteral nutrition of long duration they are important in providing essential fatty acids. OBJECTIVE: to determine the constant of elimination of two commercial lipid emulsions with similar compositions, and evaluate whether significant differences exist between them. MATERIAL, METHODS AND PATIENTS: 20 candidates for total parenteral nutrition were studied over a period of at least ten days. These patients showed no severe stress, sepsis or IRA. The patients received total parenteral nutrition for at least 3 days prior to commencing the study; 12 hours after initiation, total parenteral nutrition was administered, without lipids. Afterwards, one of the emulsions studied was infused centrally (in Y with the parenteral nutrition) at a rate of 0.15 g/kg/hour for 3 hours, 24 hours later, the other emulsion was infused under the same conditions. Commencing with one or the other was done at random, and both at 10%. Blood samples were taken at the following times:--10.0 (end of the infusion of the emulsion), 10, 30, 60 and 90 minutes, and the following parameters studied: total cholesterol (col), triglycerides (tg) and phospholipids (pl); tg, col ad pl of the VLDL, HDL and LDL, free fatty acids and lipoprotein lipase. The analytical methods employed were: ultracentrifugation with compressed air and precipitation with PEG-6000. RESULTS: significant differences were observed in the constant of elimination of total tg (2.54 +/- 0.73 in emulsion A compared to 2.8 +/- 0.66 in B), in the Kd of the VLDL tg (1.65 +/- 0.86 in A compared to 1.99 +/- 0.77 in B) and in the Kd of the VLDL P1 (0.98 +/- 0.53 in the case of A compared to 1.1 +/- 0.43 in emulsion B), no significant differences were found in the other parameters studied. The Student T was applied, and no lipase lipoprotein activity was observed. DISCUSSION: the differences found may perhaps be explained by the action of the emulgent on the intravascular metabolism of the fats. Although in both cases this is egg lecithin, the composition of this has not been studied in depth. Emulsion A = Intralipid (n. reg). Emulsion B = Tutolipid (n. reg.). PMID- 1905961 TI - [Modular enteral nutrition in pediatrics]. AB - INTRODUCTION: Modular Enteral Nutrition may be a substitute for Parenteral Nutrition in children with different pathologies. MATERIAL AND METHODS: Study of 4 children with different pathologies selected from a group of 40 admitted to the Maternal-Childrens Hospital "Valle de Hebron" in Barcelona, who received modular enteral nutrition. They were monitored on a daily basis by the Dietician Service. Modular enteral nutrition consists of modules of proteins, peptides, lipids, glucids and mineral salts-vitamins. RESULTS: 1.--Craneo-encephalic traumatisms with loss of consciousness, Feeding with a combination of parenteral nutrition and modular enteral nutrition for 7 days. In view of the tolerance and good results of the modular enteral nutrition, the parenteral nutrition was suspended and modular enteral nutrition alone used up to a total of 43 days. 2.--55% burns with 36 days of hyperproteic modular enteral nutrition together with normal feeding. A more rapid recovery was achieved with an increase in total proteins and albumin. 3.--Persistent diarrhoea with 31 days of modular enteral nutrition, 5 days on parenteral nutrition alone and 8 days on combined parenteral nutrition and modular enteral nutrition. In view of the tolerance and good results of the modular enteral nutrition, the parenteral nutrition was suspended. 4.- Mucoviscidosis with a total of 19 days on modular enteral nutrition, 12 of which were exclusively on modular enteral nutrition and 7 as a night supplement to normal feeding. DISCUSSION: We administered proteic intakes of up to 20% of the total calorific intake and in concentrations of up to 1.2 calories/ml of the final preparation, always with a good tolerance. CONCLUSIONS: Modular enteral nutrition can and should be used as a substitute for parenteral nutrition in children with different pathologies, thus preventing the complications inherent in parenteral nutrition. PMID- 1905962 TI - [Updated study of enteral nutritional diets sold in Spain]. AB - Due to the large number of enteral nutrition diets on the market in Spain, it is difficult to collect together all the information on the subject. This study sets out the criteria recommended by the Hospital of Alabama and the University of Birmingham in the evaluation of the information furnished by the laboratories that prepare the enteral nutrition diets. The study includes a compendium of the data provided by these laboratories with a view to simplifying the electron of the preparations. PMID- 1905963 TI - [Complications of TPN in gastrointestinal surgery patients]. AB - Retrospective study of a group of 77 patients subjected to gastrointestinal surgery, who received total parenteral nutrition (TPN) during the postoperative period, During the evolution of the nutrition, 76 cases with technical complications arose, one case of sepsis, 10 cases of metabolic complications and one patient with haematological complications (acute medular failure). Although a higher percentage of metabolic and haematological alterations not requiring medical or surgical treatment for correction was observed, these were indicative of the tendencies of the metabolic and haematological states of the patients. An analysis was also made of the variance, observing a direct relationship between the components of TPN and the variations of the metabolic and haematological values studied, However, these values did not correlate with the number of days during which the patients was on nutrition, and thus the technique and guidelines for administration are the most important factors which determine the presence or absence of complications during TPN. PMID- 1905964 TI - [Qualitative follow-up of parenteral nutrition. Results]. AB - The Bellvitge Hospital has a Parenteral Nutrition Unit which is centralized in the Pharmacy Department. Its mission is to prepare the nutritive mixtures for all patients who require them. Based on the diffusion of the nursing protocol (reviewed in 1986), one of the main objectives of this Unit is to define the problems arising during the administration of parenteral nutrition, and offer alternatives. Similarly, it is also necessary to offer regular information on the results of the follow-up, which can be used as a reference on a daily basis, and when compared with the quality level established, will permit us to determine where we are at all times, thus preventing us from falling into routines that will harm the service we offer. PMID- 1905965 TI - Effects of chlorpromazine on phosphatidylinositol turnover following thrombin stimulation of human platelets. AB - Thrombin stimulation of human platelets is known to result in phosphatidylinositol turnover (PI response), the activation of protein kinase C (C-kinase), and the release of arachidonic acid (AA). The authors studied the effects of chlorpromazine (CPZ) on these responses. At a concentration of 100 microM, CPZ inhibited the phosphorylation of 40,000-dalton protein through C kinase activation. CPZ failed to inhibit initial transient synthesis of 1,2 diacylglycerol (1,2-DAG) through the PI response, although it slowed the concurrent decreasing process. CPZ inhibited promotion of compensatory synthesis of phosphatidylinositol 4,5-bisphosphate (PIP2), and also inhibited the synthesis of phosphatidic acid (PA). These results suggest that phosphatidylinositol 4 monophosphate kinase and diacylglycerol kinase (DAG-kinase) may be inhibited by CPZ. CPZ also intensified the accumulation of inositol phosphates caused by the PI response, indicating possible inhibition of the phosphatases that metabolize these phosphates. Thus, CPZ partially inhibited the PI response. However, it appears likely that the inhibition of C-kinase activity by CPZ was not due to inhibition of 1,2-DAG production nor to direct inhibition of phospholipase C. CPZ also inhibited AA release. This action might be partially a result of the inhibitory effect of CPZ on PA production. PMID- 1905966 TI - Dynamic measurements of the platelet membrane glycoprotein IIb-IIIa receptor for fibrinogen by flow cytometry. I. Methodology, theory and results for two distinct activators. AB - Platelet aggregation, which occurs within seconds of activation, is generally considered to be mediated by fibrinogen binding to glycoprotein IIb-IIIa which becomes expressed as a fibrinogen receptor (FbR) on the activated platelet surface. This receptor expression has, however, only been measured to date at relatively long activation times (greater than 15 min). We have therefore developed a theoretical and experimental approach for determining FbR expression within seconds of platelet activation using flow cytometry. The fluorescently labeled IgM monoclonal antibody FITC-PAC1, was used to report on the GPIIb-IIIa receptor for Fb (FbR). Human citrated platelet-rich plasma (PRP; diluted 1:10) was incubated with adenosine diphosphate (ADP) or phorbol myristate acetate (PMA) for varying times (tau = 0-10 s, out to 60 min), followed by incubation with fluorescein isothiocyanate (FITC)-PAC1 antibody at saturating concentrations. The time course of FITC-PAC1 binding was then measured for these variously preactivated samples (different tau) from the mean platelet-bound fluorescence (Fl), determined for greater than or equal to 5 s of PAC1 addition by dilution quenching and determination of fluorescence intensity histograms with the FACSTAR or FACSCAN (Becton-Dickinson Canada, Mississauga, Ontario) flow cytometers. Both rapid, initial rate of increase in Fl (nu) (related to PAC1 on-rates) and maximal extent of increase (Flmax) were thus determined for different tau values. These measurements yield the rate of formation of FbR (k1), and both the rate (k2) and efficiency (alpha) of binding of PAC1 to FbR as a function of activator type and time of action. We have found that ADP appears to cause rapid, maximal expression of FbR within 1-3 s (k1 greater than 20 min-1), whereas PMA expresses FbR in a slow, biphasic manner (k1 - 0.01 and 0.2 min-1). However, k2 and alpha for maximal PMA activation are about two and three times greater, respectively, than for maximal ADP-activation. Moreover, k2 decreases with post ADP activation time. These differences are discussed in terms of altered FbR organization and accessibility. This kinetic approach can be widely used to analyze the dynamics and organization of molecules on cell surfaces by flow cytometry, including studies of size-dependent subpopulations (see Part II, Frojmovic, M., and T. Wong. 1991. Biophys. J. 59:828-837). PMID- 1905967 TI - Dynamic measurements of the platelet membrane glycoprotein IIb-IIIa receptor for fibrinogen by flow cytometry. II. Platelet size-dependent subpopulations. AB - Platelet aggregation has previously been shown to occur within 1 s of activation with 100 microM adenosine diphosphate (ADP) for both large (L) and small (S) platelet subpopulations, but L platelets were about twofold more sensitive and more rapidly recruited into microaggregates than were S platelets after correcting for differences in platelet surface area. Because platelet aggregation normally requires fibrinogen binding to glycoprotein IIb-IIIa receptors (FbR) expressed on the activated platelet surface, we wished to compare the kinetics and nature of FbR expression induced by ADP for L versus S platelets, and to measure size-dependent differences in FbR expression for platelets maximally activated with phorbol myristate acetate (PMA). We presented the theory and methodology in Part I (Frojmovic, M., T. Wong, and T. van de Ven. 1991. Biophys. J. 59:815-827) for measuring the rate of FbR expression (k1) and both the rate (k2) and efficiency (alpha) of binding of PAC1 to FbR as a function of activation conditions from the initial on-rate of FITC-PAC1 to FbR (V) and the maximal number of FbR expressed: these are measured, respectively, from the initial rate of increase in platelet-bound fluorescence (v) and the maximal increase in mean fluorescence (Flmax). We extended these analyses to L and S platelets, selected by electronic gating of forward scatter profiles (FSC), with corresponding fluorescence (Fl) histograms retrieved analytically. Platelet size (V) and surface area (SA), determined directly for cells separated with a cell sorter, were highly correlated with FSC, allowing v and Flmax values to be expressed per unit area of membrane for L:S comparisons. Surprisingly, ADP activation appeared to express all FbR within 1-3 s of ADP activation for both L and S platelets, whereas k1 was similar for PMA activation. In addition, L platelets maximally expressed two and three times more FbR per unit area than did S platelets when maximally stimulated, respectively, with ADP or PMA. Whereas k2 was independent of platelet size for a given activator, the efficiency of PAC1 binding (alpha), per unit area of membrane, was two times greater for L than for S platelets, for either ADP or PMA activation. Our data suggest that the FbR structure, its microenvironment, or its surface organization may vary with platelet size or activator type. Major reorganization of FbR and/or its environment appears to occur after approximately 5 min of ADP activation equally for both L and S platelets. A model is presented to account for size-dependent differences in FbR expression with implications for regulation of platelet aggregation. PMID- 1905968 TI - A critique of primary prevention of adolescent pregnancy. PMID- 1905969 TI - 17 beta-estradiol protects rats from osteopenia associated with administration of the luteinising hormone releasing hormone (LHRH) agonist, buserelin. AB - Bone loss associated with sustained administration of luteinising hormone releasing hormone (LHRH) agonists, such as buserelin, is attributed to estrogen deficiency. However, the possibility that the LHRH agonists themselves may contribute to the pathogenesis of bone thinning, has not been ruled out. The aim of the present study was to determine whether or not oral 17 beta-estradiol (300 micrograms/kg body wt/week) would fully prevent the osteopenic effect of buserelin (25 micrograms/kg body wt/day s.c.) in the rat. Four groups of animals with 45Ca-labelled skeletons were studied for 4 weeks: group 1, placebo controls; group 2, 17 beta-estradiol; group 3, buserelin; group 4, 17 beta-estradiol + buserelin. Buserelin alone lowered blood estradiol concentrations, increased bone resorption and reduced femur and total body calcium and 45Ca values. Total body calcium values (means +/- SD) were: (mg) 3405 +/- 176; 3250 +/- 282; 2813 +/- 133; 3156 +/- 452 in groups 1 to 4, respectively. Significant osteopenia was present only in group 3 (P less than 0.001). These results support the view that buserelin-mediated bone loss is due to estrogen deficiency. They do not indicate that LHRH agonists per se, play any role in causing bone thinning. PMID- 1905970 TI - [Presence of arrestin (S-antigen)-like proteins in vegetable cells]. AB - Arrestin (or S-antigen) is a protein that regulates phototransduction in photoreceptor cells of the retina. Homologous proteins have been recently detected in other, non-photosensitive, cells of vertebrates, where they are thought to be associated with other systems of signal transduction. Proteins crossreactive with retinal arrestin were detected in soluble cell extracts from Nicotiana tabacum and Chlamydomonas reinhardtii by immunoblotting using several antibodies against arrestin. Variations of the immunoreactive protein pattern were associated with the growth cycle of tobacco cells. These observations suggest that analogs of arrestin exist in the vegetal kingdom, where they could be involved in transduction processes. PMID- 1905971 TI - [SDS-PAGE analysis of surface proteins and antigens evidences high heterogenity in natural clones of Trypanosoma cruzi, correlated with isoenzyme variability]. AB - Surface protein and surface antigen patterns of 19 Trypanosoma cruzi laboratory clones, representing 17 different isozymic profiles (zymodemes), were compared by SDS-PAGE analysis. Surface protein patterns were found to be complex and heterogeneous. According to the number of common bands, we calculated similarity coefficients of surface protein patterns on the one hand, and of surface antigen patterns on the other hand, for 33 stock pairwise comparisons. In both cases, these coefficients were statistically correlated to the isozyme index of genetic identity. Such a correlation between independent genetic markers favours the clonal structure of T. cruzi natural populations previously evidenced. Moreover, we did not observe any notable differences in the surface antigen pattern among 4 T. cruzi cloned stocks precipitated by homologous as well as heterologous hyperimmune sera. The immunological significance of the molecular weight variability in surface antigen patterns among different zymodemes is discussed. PMID- 1905972 TI - [Urticating hairs of "brown-tail" moth (Euproctis chrysorrhoea L.) (Lepidoptera): preliminary studies in urban and laboratory]. AB - Urticating hairs of the brown-tail moth (Euproctis chrysorrhoea L.) are detectable in the air using apparatus designed for the collection of airborne microorganisms and pollen research studies. The hairs are produced by caterpillars and are distributed by air currents or via moths. They were collected in Bordeaux. In the laboratory a nycthemeral cycle of hair emission is observed and is correlated with the biological activities of these species. PMID- 1905973 TI - Immunoglobulin D benign monoclonal gammopathy. A case report. AB - The authors report a case, perhaps the first, of immunoglobulin D (IgD) benign monoclonal gammopathy. The patient, a 48-year-old black woman, initially had a 500 mg/dl IgD-lambda M-spike, hypercalcemia, and anemia. There was no bone pain, lytic bone lesions, or evidence of renal failure. The bone marrow showed 2.8% plasma cells with a diffuse (not nodular) IgD plasmacytosis and strong lambda predominance. Only trace amounts of free lambda light chains could be demonstrated by immunoelectrophoresis in serum and concentrated urine. The anemia responded quickly to iron therapy. Chemotherapy was not initiated. Over the 6+ years of follow-up, the patient has had no progression of clinical disease attributable to her IgD monoclonal gammopathy. The IgD M-spike has steadily decreased. PMID- 1905974 TI - Expression of common fragile sites on the X chromosome corresponds with active gene regions. AB - The expression of common chromosomal fragile sites on human chromosomes has been proposed to be a cytogenetic expression of gene activity. Distinctive patterns of expression of two common fragile sites on the human X chromosome were observed in females. The fragile site at Xp22.31, located in a band region that contains genes which escape X inactivation, was expressed on both X chromosomes. By contrast, the fragile site at Xq22.1, in a region assumed to be subject to X inactivation, was expressed almost exclusively on one X, the active X chromosome. These findings provide evidence that common fragile site expression only occurs in regions with active genes. PMID- 1905975 TI - Therapy of spontaneous lung metastasis of murine renal adenocarcinoma by systemic administration of liposomes containing the macrophage activator CGP 31362. AB - Current therapies for renal cell carcinoma have been limited by the unresponsiveness of metastatic disease to conventional treatments. Although the use of biological response modifiers as adjuvant therapy has generally not been successful against disseminated disease, in situ activation of macrophages to a tumoricidal state by liposome-encapsulated immunomodulators has been shown to eradicate metastatic cancer in murine tumor models. We, therefore, designed experiments to evaluate the ability of a new macrophage activator, CGP 31362, a synthetic bacterial cell wall analogue, to cause regression of spontaneous lung metastases in mice whose primary renal adenocarcinoma was removed by nephrectomy. Delivery of the CGP 31362 to the lungs was accomplished by its encapsulation in multilamellar phospholipid liposomes (MLV-CGP 31362). Therapy with repeated i.v. injections of MLV-CGP 31362 significantly reduced the number of lung metastases in nephrectomized mice. Therapeutic efficacy of MLV-CGP 31362 was influenced by the encapsulation ratio of CGP 31362 to total phospholipid, the dose of injected liposomes, and the frequency of administration. Optimal therapy was achieved by combining the use of i.v. MLV-CGP 31362 with the s.c. injection of recombinant murine gamma interferon. Administration of MLV-CGP 31362 prior to removal of the primary tumor and continuing postoperatively was superior to postoperative therapy alone. Several lines of evidence indicate that in situ activation of macrophages was responsible for the therapeutic effects of MLV-CGP 31362: (a) macrophages harvested from the lungs of treated mice had significant tumoricidal activity against cultured renal carcinoma cells, (b) activated macrophages, as defined by the MRP-14 marker, were present in lung tumor nodules of treated mice but not untreated mice, and (c) the in situ activation of alveolar macrophages was consistent with the in vivo deposition of 60% of radiolabeled MLV-CGP 31362 liposomes in the lungs following i.v. injection. The results reported here represent the first in vivo evaluation of MLV-CGP 31362 and offer additional evidence that macrophage combination with therapies that reduce tumor burden. PMID- 1905976 TI - [Method of multilocus enzyme electrophoresis for typing Neisseria meningitidis serogroup A in China and it's significance in epidemiology]. AB - A new, more perfect taxonomic method the multilocus enzyme electrophoresis has recently been developed to type Neisseria meningitidise serogroup A strains in China isolated from 1956-1987 and to study the epidemiological relationship of the types. 183 strains could be divided into 24 ET types, among which ETs, ET18 were found predominant in epidemics occurred in last two decades respectively. Different predominant ET types were found in different epidemic period and only one predominant ET type existed in each period. The cases and carriers occurred in the interepidemic stage and in some places. Their strains belonged to some endemic ET types. PMID- 1905977 TI - Development of cell polarity in budding yeast. AB - The development of cell polarity involves virtually every aspect of cell biology. Yeast are less complex than cells traditionally used for studies on cell polarity and are amendable to sophisticated genetic analysis. This has resulted in a growing number of molecular markers for yeast cell polarity and an increasingly well-defined progression of molecular events required for bud formation. Together, these factors provide a favorable context in which to understand how the interplay between a large number of processes can polarize a cell. Many genes required for morphogenesis have been identified, and genetic interactions provide evidence that the products of these genes function together. Studies on cell polarity development in S. cerevisiae have demonstrated a requirement for small GTP-binding proteins and have established functional relationships between temporally coincident events. With the continued identification and analysis of genes required for morphogenesis, and the pursuit of these studies on a cytological and biochemical level, studies on yeast will continue to contribute to our understanding of cell polarity development. PMID- 1905978 TI - Bacterial entry into eukaryotic cells. PMID- 1905979 TI - Entry of L. monocytogenes into cells is mediated by internalin, a repeat protein reminiscent of surface antigens from gram-positive cocci. AB - We report the identification of a previously unknown gene, inlA, which is necessary for the gram-positive intracellular pathogen Listeria monocytogenes to invade cultured epithelial cells. The inlA region was localized by transposon mutagenesis, cloned, and sequenced. inlA was introduced into Listeria innocua and shown to confer on this normally noninvasive species the ability to enter cells. Sequencing of inlA predicts an 80 kd protein, internalin. Two-thirds of internalin is made up of two regions of repeats, region A and region B, and the C terminus of the molecule is similar to that of surface proteins from gram positive cocci. Internalin has a high content of threonine and serine residues, and the repeat motif of region A has regularly spaced leucine residues. As evidenced by Southern blot analysis, inlA is part of a gene family. One of them is the gene situated directly downstream of inlA, called inlB, which also encodes a leucine-rich repeat protein. PMID- 1905980 TI - The regulatory light chain of nonmuscle myosin is encoded by spaghetti-squash, a gene required for cytokinesis in Drosophila. AB - Two independent approaches to understanding the molecular mechanism of cytokinesis have converged on the gene spaghetti-squash (sqh). A genetic screen for mitotic mutants identified sqh1, a mutation that disrupts cytokinesis, which was then cloned by transposon tagging. Independently, the gene that encodes the regulatory light chain of the biochemically defined nonmuscle myosin (MRLC-C) was also cloned. We show here that sqh encodes MRLC-C and that in sqh1 mutants, the level of stable light chain transcript is greatly reduced. Reversion by transposon excision or transformation with a wild-type copy of the sqh transcription unit rescues cytokinesis failure and other defects in sqh1. Vertebrate homologs of MRLC-C are phosphorylatable and regulate myosin activity in vitro. These studies provide genetic proof that MRLC-C is required for cytokinesis, suggest a role for the protein in regulating contractile ring function, and establish a genetic system to evaluate its function. PMID- 1905981 TI - Yeast BUD5, encoding a putative GDP-GTP exchange factor, is necessary for bud site selection and interacts with bud formation gene BEM1. AB - Cells of the yeast S. cerevisiae choose bud sites in an axial or bipolar spatial pattern depending on their cell type. We have identified a gene, BUD5, that resembles BUD1 and BUD2 in being required for both patterns; bud5- mutants also exhibit random budding in all cell types. The BUD5 nucleotide sequence predicts a protein of 538 amino acids that has similarity to the S. cerevisiae CDC25 product, an activator of RAS proteins that catalyzes GDP-GTP exchange. Two potential targets of BUD5 are known: BUD1 (RSR1) and CDC42, proteins involved in bud site selection and bud formation, respectively, that have extensive similarity to RAS. We also show that BUD5 interacts functionally with a gene, BEM1, that is required for bud formation. This interaction provides further support for the view that products involved in bud site selection guide the positioning of a complex necessary for bud formation. PMID- 1905982 TI - Functional cloning of BUD5, a CDC25-related gene from S. cerevisiae that can suppress a dominant-negative RAS2 mutant. AB - By searching for genes that behave like CDC25 of S. cerevisiae in their ability to counteract a dominant-negative RAS2 mutant in a wild-type RAS-dependent manner, we have isolated a CDC25-like homolog, BUD5. BUD5 is tightly linked to the MAT locus. Although overexpressed BUD5 cannot substitute for CDC25 function, we present evidence that its gene product can bind to the guanine nucleotide binding-deficient RAS2val19ala22 gene product and thereby counteract its dominant negative effect. We propose that BUD5 is a member of a family of CDC25-related genes that encode activators of RAS and RAS-like proteins. PMID- 1905983 TI - The HIV core protein p24 inhibits interferon-gamma-induced increase of HLA-DR and cytochrome b heavy chain mRNA levels in the human monocyte-like cell line THP1. AB - Cells from the human monocytic cell-line THP1 were incubated prior to activation with IFN-gamma or LPS with varying amounts of p24, the main product of the HIV gag gene and the major component of the virus core. The IFN-gamma-dependent increase of mRNA for HLA-DR and for the heavy chain of cytochrome b was markedly decreased by p24 but not by gp120. This effect was abrogated by anti-p24 antibodies. On the other hand, preincubation of THP1 cells with p24 did not affect the accumulation of the LPS-dependent mRNA for TNF alpha and IL1-beta. These results indicate that p24 at concentrations similar to those found in the serum of HIV-infected individuals specifically affects IFN-gamma-induced activation markers. PMID- 1905984 TI - Interferon-gamma-treated murine macrophages inhibit growth of tubercle bacilli via the generation of reactive nitrogen intermediates. AB - Murine peritoneal macrophages were isolated and their ability to restrict growth of a virulent Mycobacterium tuberculosis in response to IFN-gamma was assessed in various conditions. Doses of IFN-gamma ranging from 10 to 100 U stimulated high levels of antimycobacterial activity, as seen by inhibition of growth. Addition of catalase, superoxide dismutase, and other scavengers of reactive oxygen species before infection failed to abrogate this restriction of growth, suggestive of a lack of involvement of reactive oxygen species in this phenomenon. Addition of arginase before infection inhibited the bacteriostatic ability of IFN-gamma-pulsed macrophages as did addition of NG-monomethyl L arginine, an inhibitor of the synthesis of inorganic nitrogen oxide. In both cases, this inhibition was reversed by adding excess L-arginine in the medium. Moreover, nitrite production in macrophages was correlated with their ability to restrict tubercle bacilli growth. These results imply that nitric oxide or another inorganic nitrogen oxide is an important effector molecule in restricting growth of M. tuberculosis in IFN-gamma-pulsed murine macrophages. PMID- 1905985 TI - Adhesion characteristics of human interleukin 2-activated natural killer cells. AB - Culture of human monocyte-depleted peripheral blood mononuclear cells with recombinant IL2 (rIL2) induced adherence to plastic by 24 hr and subsequent proliferation in a subpopulation of lymphocytes with phenotypic and functional characteristics of activated natural killer (NK) cells. Purified human NK cells activated in the presence of IL2 for 24 hr upregulated the expression of the CD11c (p150.95) and CD11a antigen but not other cellular adhesion molecules (CAM). After further incubation with IL2, NK cells displayed upregulation of all of the antigens in the CD11/CD18 family of CAM. The process of adhesion was strictly dependent on culture in the presence of IL2, divalent cations, and active cellular metabolism. Adhesion also was dependent on expression of CAM on the cell surface, since monoclonal antibodies to CAM inhibited adhesion of activated NK cells to varying degrees (from 50 to 80%). An antibody (LeuM5) to the CD11c antigen (p150.95) gave the highest level of inhibition, and anti-CD11a (LFA-1) also was inhibitory, while anti-CD56 (NKH1) or anti-CD11b did not interfere with adhesion to plastic. Anti-CD11c was also the most effective in initiating the detachment of adherent-phase NK cells. Antibodies to CD18 or CD2 antigen also inhibited binding of NK cells to plastic. The blocking effects of anti-CD2 and anti-CD11a were additive in this system. On the surface of plastic adherent and motile NK cells, all CAM except the CD56 antigen had a polar or bipolar distribution, as determined by staining with anti-CAM antibodies. Surface antigens CD11b, CD11c, CD2, and CD18 on nonadherent NK cells were clustered at the cellular poles by both immunofluorescence and immunogold electron microscopy, whereas CD11a (LFA-1) and CD56 antigens were distributed diffusely. CAM, especially CD11c, were also detected in cytoplasmic granules by immunostaining in IL2-activated NK cells. Thus, CAM may be stored in granules, allowing for their rapid transfer to the cell membrane in response to activation. Our results indicate that CAM are upregulated in IL2-activated NK cells and that some of these molecules (e.g., CD11c) play an important role in the development of plastic adherence by a subpopulation of these cells. PMID- 1905986 TI - [Anatomopathologic diagnosis of parasitosis in Congo]. AB - In the part ten years, 9,650 anatomopathologic examinations have been carried out in the National Laboratory of Histopathology for Public Health in Brazzaville: 250 cases of parasitic infestation were diagnosed. In order of frequency were noted; 144 cases of bilharzia due to Schistosoma haematobium with 75 genito urinary localisations and 51 appendicular cases, 31 cases of onchocercosis with a majority of subcutaneous nodules (17), 17 cases of digestive helminthiasis all locate in the ileo-caecal-appendix and discovered during systematic appendicular exploration, 13 cases of colitic or recto-sigmoidal amebiasis. These results point out 68 cases of appendicular parasitism. This should be in favour of more systematic anatomopathological examination of the ileo-caecal appendix both in tropical and in temperate regions. PMID- 1905987 TI - Haemodynamic changes during the apnoea test for diagnosis of brain death. AB - Haemodynamic responses to the apnoea test for the diagnosis of brain death were investigated in nine patients with severe head injury or cerebrovascular disease. To prove apnoea, the ventilator was disconnected for ten minutes and oxygen was insufflated to avoid hypoxaemia. No respiratory movement was seen in any patient. Ten minutes after disconnecting the ventilator, PaCO2 was increased to 78 +/- 3 mmHg and pH was reduced to 7.17 +/- 0.02. Adequate oxygenation was maintained in all patients. Cardiac output increased from 4.8 +/- 0.7 to 5.7 +/- 0.8 L.min-1 (P less than 0.05), and mean pulmonary artery pressure increased from 11 +/- 1 to 17 +/- 2 mmHg (P less than 0.01). However, mean arterial pressure, heart rate, pulmonary artery wedge pressure and right atrial pressure did not change. Plasma catecholamines were measured in three patients. Plasma norepinephrine concentrations increased in all three patients but the changes in plasma epinephrine were minimal. These circulatory responses to acute hypercapnia were less than those reported in awake volunteers and in patients during general anaesthesia. However, since plasma norepinephrine concentration increased during the test, some sympathoadrenal response, probably of spinal origin, was present, and may have prevented the direct depressant circulatory effects of acute hypercapnia. In conclusion, the apnoea test did not produce haemodynamic disturbances when respiratory acidosis was limited to a pH 7.17 +/- 0.02 and PaCO2 60-80 mmHg. PMID- 1905988 TI - Pulmonary gas exchange and ventilation-perfusion relationships during hypocapnia and thoracotomy in anaesthetized dogs. AB - The effects of hypocapnia and thoracotomy, both individually and combined, on pulmonary gas exchange and distribution of ventilation-perfusion ratio (Va/Q) were studied in anesthetized and paralyzed mongrel dogs by the six inert gas elimination technique. Normocapnia (PaCO2 35 mmHg) and hypocapnia (PaCO2 20 mmHg) were produced sequentially by varying the inspired CO2 concentration. Thoracotomy was performed at the fourth intercostal space. When ventilation was changed from normocapnia to hypocapnia without thoracotomy, PaO2 decreased from 160 +/- 10 to 147 +/- 11 mmHg and Qs/Qt increased from 0.0 +/- 0.0 to 0.6 +/- 0.7%. However, no change was observed in perfusion distribution following thoracotomy during normocapnia, PaO2 decreased from 160 +/- 10 to 113 +/- 15 mmHg together with a shift of perfusion toward the low Va/Q region. However, no change was observed in Qs/Qt. When ventilation was changed from normocapnia to hypocapnia with thoracotomy, PaO2 decreased from 113 +/- 15 to 98 +/- 12 mmHg and Qs/Qt increased from 0.3 +/- 0.8 to 3.4 +/- 2.0%. After thoracotomy, a shift of perfusion toward the low Va/Q region was observed, which was probably responsible for the decrease in PaO2. The decrease in PaO2 during hypocapnia was due to an increase in the true shunt rather than the development of low Va/Q region. Hypocapnia combined with thoracotomy produced a further reduction of PaO2 and a greater increase in Qs/Qt. PMID- 1905989 TI - Pulmonary effects of continuous endotoxin infusion in the rat. AB - A major hindrance to the elucidation of the pathogenesis of the adult respiratory distress syndrome (ARDS) is the lack of an animal model consistent with the clinical course in humans. A continuous intravenous infusion of endotoxin (LPS) over a several day period was used to more closely parallel the clinical setting. Male Sprague-Dawley rats infused with LPS via indwelling right atrial catheters become tachypneic, lethargic and anorectic with a steady loss in body weight. Serial blood gas analyses demonstrate an early respiratory alkalosis followed by increasing acidosis and hypoxia. Lungs demonstrate 1) pulmonary leukoaggregation, 2) interstitial and intraalveolar edema, 3) Type I pneumocyte injury, 4) proliferation of Type II pneumocytes, and 5) thickening of the microvascular walls. Differential neutrophil count in bronchoalveolar lavage (BAL) fluid increased from 1% to a peak of 59.1% +/- 3.0% and protein content was elevated. A prolonged infusion of LPS in the rat produces a lung injury which mimics many of the pathophysiologic and histologic features associated with sepsis-induced ARDS in humans. PMID- 1905990 TI - [Indirect immunoperoxidase staining technique with frozen sections of schistosome for serodiagnosis of latent schistosomiasis]. AB - Indirect immunoperoxidase staining technique using frozen sections of adult worm as antigen (IIP-AWA) was carried out to detect antibodies against schistosome antigens (AWAb) for the diagnosis of existing infection of schistosomiasis in COPT positive cases. Sera from 229 COPT positive and 135 COPT negative cases in Shanghai County, where schistosomiasis had been eradicated for more than 5 years, were tested. Sera from 122 patients with positive stool hatching from an endemic area were served as positive controls. The positive rates of the three groups were 96.9%, 5.2%, and 100% respectively. The staining pattern of the worm sections was mainly diffused at serum dilutions 1:4 to 1:16. 149 sero-positive cases were treated with pyquiton (60 mg/kg.2d) and re-examined 1, 1.5, and 2.5 years post-treatment. The negative conversion rate of IIP-AWA was considerably higher than that of COPT (80% vs. 61.1%) at the first year, but no significant difference was observed after 2.5 years (85.5% vs. 83.6%). With the decreasing antibody titer, the staining pattern of worm sections changed from diffused to focal pattern, mostly in the gut. The results suggest that the presence of detectable AWAb in untreated patients or patients treated 2 years ago with pyquiton possibly indicate latent schistosomiasis. IIP-AWA is of practical value in screening populations for latent schistosomiasis in areas where the disease had been under control. PMID- 1905991 TI - Cryoprecipitate for uremic bleeding. PMID- 1905992 TI - Improved FACS-Gal: flow cytometric analysis and sorting of viable eukaryotic cells expressing reporter gene constructs. AB - The previously reported FACS-Gal assay (Nolan et al., Proc Natl Acad Sci USA 85:2603-2607, 1988) measures E. coli lacZ-encoded beta-galactosidase activity in individual viable eukaryotic cells for a variety of molecular and cellular biological applications. Enzyme activity is measured by flow cytometry, using a fluorogenic substrate, which is hydrolyzed and retained intracellularly. In this system, lacZ serves both as a reporter gene to quantitate gene expression and as a selectable marker for the fluorescence-activated sorting of cells based on their lacZ expression level. This report details the following improvements of the original assay: 1) use of phenylethyl-beta-D-thiogalactoside, a competitive inhibitor, to inhibit beta-galactosidase activity; 2) reduction of false positives by two-color measurements; and 3) inhibition of interfering mammalian beta-galactosidases by the weak base chloroquine. We found an exponential relationship between fluorescence generated by beta-galactosidase in this assay and the intracellular concentration of beta-galactosidase molecules. Finally, we report conditions for optimal loading of the substrate (FDG) and retention of the product, fluorescein. Under these conditions, we found uniform loading of FDG in all cells of a clone in individual experiments. Together, these improvements make FACS-Gal an extremely powerful tool for investigation of gene expression in eukaryotic cells. PMID- 1905993 TI - [Changes in amphibian behavior after transplantation into the brain of neural anlage cells from Drosophila]. PMID- 1905994 TI - [The effect of naloxone on brain development and behavior in Drosophila melanogaster]. PMID- 1905995 TI - [Percutaneous endoscopic gastrostomy]. PMID- 1905996 TI - [Relationship between reproductive and productive performance in poultry flocks]. AB - The author analyses the interrelationship between the hygienic prerequisites of reproduction and performance in poultry farming, with regard to their impact on human health. The main factors influencing the hatching rate of poultry eggs are reviewed along with their epizootiological and economic aspects, and the possibilities of the prevention of egg-transmitted diseases are discussed. PMID- 1905997 TI - Inhibition of NO3-, NH4+, and PO4(3-) uptake in Anabaena doliolum exposed to a petroleum oil. AB - The aqueous extract of Assam crude inhibited the uptake of NO3-, NH4+, and PO4(3 ) in Anabaena doliolum and the response was essentially concentration dependent. Inhibition was most severe for the uptake of NH4+ followed in decreasing order by PO4(3-) and NO3-. Uptake of nutrients was competitively inhibited as in all the cases oil extract did not change Vmax; however, apparent Km was increased. The nature of oil components competing with nutrient ions is not certain at present. Oil-induced inhibition of nutrient uptake in cyanobacteria might be reversed in eutrophic waters rich in nutrients. PMID- 1905998 TI - Influence of the feeding frequency on nutrient utilization in man: consequences for energy metabolism. AB - A study was conducted to investigate whether there is a diurnal pattern of nutrient utilization in man and how this is affected by meal frequency to explain possible consequences of meal frequency for body weight regulation. When the daily energy intake is consumed in a small number of large meals, there is an increased chance to become overweight, possibly by an elevated lipogenesis (fat synthesis and accumulation) or storage of energy after the meal. Thirteen subjects, two males and eleven females, were fed to energy balance in two meals per day (gorging pattern) and seven meals per day (nibbling pattern) over 2-day intervals. On the second day on each feeding regimen, the diurnal pattern of nutrient utilization was calculated from simultaneous measurements of oxygen consumption, carbon dioxide production and urinary nitrogen excretion over 3 h intervals in a respiration chamber. A gorging pattern of energy intake resulted in a stronger diurnal periodicity of nutrient utilization, compared to a nibbling pattern. However, there were no consequences for the total 24 h energy expenditure (24 h EE) of the two feeding patterns (5.57 +/- 0.16 kJ/min for the gorging pattern; 5.44 +/- 0.18 kJ/min for the nibbling pattern). Concerning the periodicity of nutrient utilization, protein oxidation during the day did not change between the two feeding patterns. In the gorging pattern, carbohydrate oxidation was significantly elevated during the interval following the first meal (ie from 1200 h to 1500 h, P less than 0.01) and the second meal (ie from 1800 h to 2100 h, P less than 0.05). The decreased rate of carbohydrate oxidation observed during the fasting period (from rising in the morning until the first meal at 1200 h), was compensated by an increased fat oxidation from 0900 to 1200 h to cover energy needs. In the nibbling pattern, carbohydrate and fat oxidation remained relatively constant during the active hours of the day.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1905999 TI - Somatic hypermutation of immunoglobulin kappa may depend on sequences 3' of C kappa and occurs on passenger transgenes. AB - We have compared the pattern of somatic mutation in different immunoglobulin kappa transgenes and suggest that an element(s) located between 1 kb and 9 kb 3' of C kappa is necessary for somatic hypermutation of the antibody V gene. The sequences of transgenic and endogenous Ig V regions were determined in antigen specific B cell hybridomas specific for 2-phenyloxazolone from independent lines of hyperimmunized transgenic mice. We analysed somatic mutation of the transgene both in hybridomas in which the transgenic kappa chain contributes to the antigen combining site as well as in hybridomas in which the transgene is a passenger with the expressed antibody being composed of endogenously-encoded heavy and light chains. In both cases, nucleotide changes in the transgene are correctly targeted to the V region and are absent from the C region. They accumulate at a similar rate to that in the endogenous Ig genes within the same cell and we find that, irrespective of whether or not the transgene kappa is directly selected by antigen, somatic mutation occurs at a similar rate and involves only single base substitutions. Furthermore, the pattern of mutations in passenger transgenes gives information about the intrinsic sequence specificities of the somatic hypermutation mechanism. PMID- 1906000 TI - Unidirectional theta replication of the structurally stable Enterococcus faecalis plasmid pAM beta 1. AB - Numerous bacterial replicons remain poorly characterized due to difficulties in localization of the replication origin. We have circumvented this problem in the characterization and fine mapping of the origin of plasmid pAM beta 1 by exploiting the Bacillus subtilis termination signal, terC. In terC-containing derivatives, theta-form molecules with two invariant endpoints accumulate. The endpoints, which correspond to plasmid origin and terC, were mapped with single nucleotide precision. Analysis of the replication intermediates of wild-type molecules by two-dimensional gel electrophoresis confirmed the location of the plasmid origin. Our results demonstrate that pAM beta 1 replication proceeds unidirectionally by a theta mechanism. This work confirms the use of termination signals to localize origins, suggests that termination in B. subtilis occurs by a mechanism similar to that of Escherichia coli and establishes that in addition to rolling circle replicating plasmids, Gram positive bacteria harbour plasmids which replicate by a theta mechanism. PMID- 1906001 TI - Unregulated expression of c-Jun or c-Fos proteins but not Jun D inhibits oestrogen receptor activity in human breast cancer derived cells. AB - We present evidence that oestrogen receptor activity in human MCF-7 breast cancer cells is reduced by over-expression of c-Jun or c-Fos proteins and to a lesser extent by Jun B overexpression. In contrast, overexpression of Jun D protein does not affect the activity of the oestrogen receptor. A region of c-Jun found to be required for repression of oestrogen receptor activity is located outside the DNA binding domain and is not conserved among the three Jun proteins. Finally, we suggest that c-Jun and c-Fos act independently to inactivate the oestrogen receptor. PMID- 1906002 TI - Cultured human fibroblasts contain a large pool of precursor beta 1-integrin but lack an intracellular pool of mature subunit. AB - Previous work has shown the presence of an important intracellular pool of beta 1 integrin subunit in human skin fibroblasts as detected with monoclonal antibody DH12 [De Strooper, B., Van der Schueren, B., Jaspers, M., Saison, M., Spaepen, M., Van Leuven, F., Van den Berghe, H. & Cassiman, J. J. (1989) J. Histochem. Cytochem. 37,299-307]. To analyze this more quantitatively, a radioimmunoassay with radioiodinated monoclonal antibody was developed. The total amount of specific binding sites for monoclonal antibody DH12 on skin fibroblasts was between 0.8-1.5 x 10(6)/cell. After permeabilizing the cells with digitonin, a threefold increase in specific binding was observed, which suggested that about 60% of the total amount of beta 1-subunit was localized intracellularly. From pulse/chase experiments, it was deduced that an important pool of precursor subunit, as defined by its sensitivity to endoglycosidase treatment, existed in fibroblasts. Since in steady-state-labeling conditions, at least three to four times more precursor than mature subunit was immunoprecipitated with monoclonal antibody DH12, we suggested that the intracellular pool of beta 1-integrin subunit is mainly precursor pool. This precursor pool contains a degradation compartment and a maturation compartment. Other investigators have found evidence for a recirculating pool of mature integrin in Chinese hamster ovary cells. Therefore, the presence of a recirculating pool of integrin in human fibroblasts was also considered. The data obtained with mAb DH12 showed that less than 10% of the surface pool of integrin was internalized by endocytosis. Since, however, cross linking of beta 1-integrins with polyclonal antibodies leads to rapid endocytosis of most of the integrin, it remains possible that the quantitatively small effect was actually an artefact induced by the divalent mAb. We conclude that the intracellular pool of beta 1-integrins observed in our previous studies consists of precursor and that in skin fibroblasts no mature beta 1-integrin is available intracellularly for rapid quantitative modulations at the cell surface. PMID- 1906003 TI - Polymorphic flecainide disposition under conditions of uncontrolled urine flow and pH. AB - The pharmacokinetics of R- and S-flecainide have been determined in five poor (PM) and five extensive (EM) metabolisers of sparteine/debrisoquine under conditions of uncontrolled urine flow and pH. The half-lives of R- and S flecainide in PMs (R 19.3 h; S 16.1 h) were approximately twice those observed in EMs (R 8.8 h; S 9.1 h). The apparent oral clearances of R- and S-flecainide were lower in PMs (R 313 ml.min-1; S 379 ml.min-1) than in EMs (R 783 ml.min-1; S 828 ml.min-1). The renal clearance, however, was comparable for both enantiomers in both EMs and PMs, and therefore the phenotypic differences in flecainide disposition observed must be due to differences in metabolic clearance. The nonrenal clearance of both enantiomers was significantly lower in poor (R 123 ml.min-1; S 201 ml.min-1) relative to extensive metabolisers (R 533 ml.min-1; S 586 ml.min-1). The partial clearance to the two major metabolites meta-O dealkylated flecainide (MODF) and the meta-O-dealkylated lactam of flecainide (MODLF) was significantly lower in poor (62 ml.min-1) than extensive (267 ml.min 1) metabolisers. The impairment in flecainide metabolism in poor metabolisers of sparteine/debrisoquine has therefore been confirmed. Under conditions reflecting the clinical situation the difference in disposition between EMs and PMs would be considerable. However, it may be predicted that at standard doses concentrations greater than 1000 ng.ml-1 would not be attained in the PMs studied.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1906005 TI - Glibenclamide relaxes vascular smooth muscle constriction produced by prostaglandin F2 alpha. AB - The present study has demonstrated: (1) glibenclamide can reduce resting tension in canine cerebral arteries but has no effect on resting tension in the rat aorta; (2) glibenclamide can relax prostaglandin F2 alpha-induced contractions in the rat aorta, and in canine femoral, mesenteric, renal, coronary, basilar and middle cerebral arteries; (3) the relaxation produced by glibenclamide in rat aorta is comparable to that of glyceryl trinitrate and stronger than that of papaverine; (4) canine femoral arteries are less sensitive to glibenclamide than the other arteries; (5) in cerebral arteries glibenclamide was as effective as papaverine, but less effective than glyceryl trinitrate; (6) the actions of glibenclamide on cerebral arteries are not mediated by cGMP as they were not blocked by methylene blue, an inhibitor of guanylate cyclase; (7) the effects of glibenclamide are not endothelium-dependent. The mechanism by which glibenclamide produces relaxation is not clear; while the drug is known to block ATP-dependent potassium channels, in vascular smooth muscle this would cause contraction, not dilation. The action of glibenclamide may be at the level of the receptor or the signal transduction process. PMID- 1906004 TI - Measurement of human cerebral monoamine oxidase type B (MAO-B) activity with positron emission tomography (PET): a dose ranging study with the reversible inhibitor Ro 19-6327. AB - Eight normal subjects (3 females and 5 males) were studied using intravenous L [11C] deprenyl and positron emission tomography. In a single blind study one subject received tracer alone, one subject received an oral pre-dose of 20 mg of L-deprenyl and 6 subjects received oral pre-doses of 10 to 50 mg of a novel reversible MAO-B inhibitor (Ro 19-6327). Dynamic PET scans beginning 12 h after the oral dose were collected over 90 min and arterial blood was continuously sampled. Data analysis was modelled for two tissue compartments and using an iterative curve fitting technique the value of the rate constant for irreversible binding of L-[11C] deprenyl to MAO-B (k3) in whole brain was obtained for each subject. The dose response curves obtained indicated that a dose of at least 0.48 mg.kg-1 of Ro 19-6327 was necessary for greater than 90% decrease in whole brain k3. Inhibition of MAO-B in platelets isolated from blood samples taken at the time of scanning correlated strongly with decrease in whole brain k3 (r = 0.949). The results indicate that PET can be used to determine the dose of Ro 19-6327 necessary to inhibit greater than 90% of brain MAO-B. This technique is an attractive alternative to traditional large scale patient-based dose-finding studies. Moreover it is shown that inhibition of platelet MAO-B can be used as a marker for central MAO-B inhibition with Ro 19-6327. PMID- 1906006 TI - Contraction and prostaglandin biosynthesis by myometrium from non-pregnant and pregnant rabbits in response to adenosine 5'-triphosphate. AB - In both non-pregnant and pregnant rabbit myometrial strips, adenosine 5' triphosphate (ATP) produced contractions in a concentration-dependent manner. Furthermore, ATP (100 microM and 1 mM) produced an initial rapid twitch-like contraction followed by augmented spontaneous motility. These contractile responses of strips from pregnant rabbits to ATP were more marked than those of strips from non-pregnant rabbits. The pD2 values for the contractile response to ATP were 5.20 and 6.70 in strips from non-pregnant and pregnant rabbits, respectively. Treatment with indomethacin did not affect the initial rapid twitch like contraction, but inhibited the augmented spontaneous motility. ATP also increased the synthesis of prostaglandins (PGs) and thromboxane B2 (TXB2) in a concentration-dependent manner in the following order: 6-keto-PGF1 alpha greater than PGE2 greater than PGF2 alpha greater than TXB2. The increase in the synthesis of cyclooxygenase products induced by ATP was more marked in strips from pregnant rabbits than in strips from non-pregnant rabbits. ATP and melittin stimulated arachidonic acid, phosphatidic acid and diacylglycerol formation in strips from both non-pregnant and pregnant rabbits. These results indicate that ATP stimulates PGs and TXB2 synthesis and phosphatidylinositol hydrolysis through an effect on P2-purinoceptors and consequently augments myometrial contractility in both non-pregnant and pregnant rabbits. PMID- 1906007 TI - Effects of lithium ion on ADP ribosylation of inhibitory GTP-binding protein by pertussis toxin, islet-activating protein. AB - Studies were made on the effects of Li+ on ADP ribosylation of inhibitory GTP binding (Gi) protein by islet-activating protein (IAP), pertussis toxin. The ADP ribosylation of 40-41 kDa proteins of the membranes of rat cardiac ventricular cells by IAP was reduced by the addition of a nonhydrolyzable analog of guanine nucleotide, GTP gamma S, indicating that these proteins included Gi protein. The addition of LiCl (0.5-10 mM) to the membrane fractions of the cells attenuated the ADP ribosylation of the Gi protein of the cell membranes by IAP dose dependently. The effects of LiCl were reversible. Of the monovalent ions tested, Li+ inhibited the ADP ribosylation of the protein by IAP most strongly. The effects of LiCl (2 mM) were observed even in the presence of 150 mM KCl. Moreover, LiCl decreased the ADP ribosylation of purified Gi protein by IAP. These results support that Gi proteins are one of the targets for the therapeutic effects of lithium. PMID- 1906008 TI - Lithium decreases Gs, Gi-1 and Gi-2 alpha-subunit mRNA levels in rat cortex. PMID- 1906009 TI - Effect of in vivo pre-treatment with oestradiol and either GnRH, GnRH agonistic analog or GnRH antagonistic analog on GnRH-stimulated secretion of LH in vitro. AB - In vivo treatment with GnRH or with GnRH agonistic analog (AG), but not with GnRH antagonistic analog (ANT), depleted the LH stores of the rat pituitary gland. This depletion was potentiated by oestradiol. Oestradiol augmented the in vitro LH response of the pituitary gland to GnRH. This augmenting effect of oestradiol became smaller with increasing rates of in vivo administration of GnRH or AG, but not with ANT. With respect to both depletion of the LH stores and suppression of the augmenting effect of oestradiol, AG ist about 20 times as potent as GnRH. PMID- 1906010 TI - L-tyrosine induces tyrosinase expression via a posttranscriptional mechanism. AB - Exposure of hamster amelanotic melanoma cells to L-tyrosine caused a time dependent increase of tyrosinase protein concentrations, tyrosinase activity and level of cell pigmentation. In contrast, Northern blot analysis using mouse tyrosinase cDNA showed a steady level of tyrosinase mRNA. Thus in hamster melanoma cells the stimulation of intracellular tyrosinase concentration by L tyrosine is mediated mainly via a posttranscriptional mechanism. PMID- 1906011 TI - Protein kinase C dependent and independent activation of phospholipase A2 under calcium ionophore (A23187) exposure in rabbit pulmonary arterial smooth muscle cells. AB - Exposure of rabbit pulmonary arterial smooth muscle cells to the calcium ionophore A23187, dose-dependently stimulates arachidonic acid (AA) release and phospholipase A2 (PLA2) activity. The protein kinase C (PKC) inhibitor, sphingosine does not prevents AA release and PLA2 activity caused by low doses of A23187. In contrast, sphingosine markedly prevents AA release and PLA2 activity caused by higher doses of A23187. PKC activity profile indicates that treatment of the cells with low doses of A23187 does not cause significant alteration of PKC translocation from cytosol to membrane whereas higher concentrations of the ionophore dose-dependently enhance PKC translocation from cytosol to membrane in the smooth muscle cells. PMID- 1906012 TI - An NAD-specific glutamate dehydrogenase from cyanobacteria. Identification and properties. AB - The unicellular cyanobacterium Synechocystis sp. PCC 6803 presents a hexameric NAD-specific glutamate dehydrogenase with a molecular mass of 295 kDa. The enzyme differs from the NADP-glutamate dehydrogenase found in the same strain and is coded by a different gene. NAD-glutamate dehydrogenase shows a high coenzyme specificity, catalyzes preferentially glutamate formation and presents Km values for ammonium, NADH and 2-oxoglutarate of 4.5 mM, 50 microM and 1.8 mM respectively. An animating role for the enzyme is discussed. PMID- 1906013 TI - A catalytic role for threonine-12 of E. coli asparaginase II as established by site-directed mutagenesis. AB - A threonine-12 to alanine mutant of E. coli asparaginase II (EC 3.5.1.1) has less than 0.01% of the activity of wild-type enzyme. Both tertiary and quaternary structure of the enzyme are essentially unaffected by the mutation; thus the activity loss seems to be the result of a direct impairment of catalytic function. As aspartate is still bound by the mutant enzyme, Thr-12 appears not be involved in substrate binding. PMID- 1906014 TI - Chemical and functional analysis of components of adenylyl cyclase from human platelets treated with phorbolesters. AB - Human platelets, prelabeled with [32P]phosphate were treated with tetradecanoylphorbol acetate (TPA) for 5 min at 37 degrees C. Phosphorylation of the components of adenylyl cyclase was determined in membranes using specific antibodies against G-proteins and the catalytic moiety. Less than 0.01 mol of [32P]phosphate/mol could be detected in immunoprecipitates using antibodies against sequences within the alpha-subunit of the GTP binding protein Gi. TPA, however, caused the incorporation of 0.67-1.1 mol of [32P]phosphate per mol of catalyst while 0.13-0.2 mol were found in the absence of TPA. Lack of modification of the alpha-subunit of Gi was also indicated by the results of reconstitution experiments with purified Gi alpha from bovine brain: adenylyl cyclase in membranes from untreated platelets was significantly more inhibited by added G1 alpha, than that from TPA treated cells. While beta, gamma-subunits were like-wise inhibitory no difference dependent on platelet-pretreatment could be observed. PMID- 1906015 TI - Expression of D-mannose binding sites on human spermatozoa: comparison of fertile donors and infertile patients. AB - OBJECTIVE: The hypothesis that defective expression of D-mannose binding sites (presumptive elements of the sperm-zona pellucida binding mechanism) is related to male infertility was tested. DESIGN: Experiments were performed on sperm samples from two groups of men classified, respectively, as fertile and infertile, based on their reproductive history. SETTING: The study was carried out in an andrologic laboratory of a University Hospital. PATIENTS, PARTICIPANTS: Fertile men were healthy sperm donors; infertile men were patients with fertility problems. INTERVENTIONS: D-mannose binding sites were visualized by fluorescence microscopy using a mannosylated neoglycoprotein probe. MAIN OUTCOME MEASURES: The hypothesis as reported in the objective section was formulated before data collection and was not modified thereafter. RESULTS: Sperm from fertile men displayed a characteristic pattern of changes in the expression of D-mannose binding sites during in vitro capacitation. This pattern was altered in sperm from infertile men. CONCLUSIONS: If the relationship between defective expression of D-mannose binding sites and decreased sperm fertilizing ability is validated by parallel tests of sperm-zona binding, it may be used for development of chemical tests replacing the current ones using human zonae pellucidae. PMID- 1906016 TI - Effect of a gonadotropin-releasing hormone agonist and gonadotropins on ovarian follicles in cynomolgus monkey: a model for human ovarian hyperstimulation. AB - STUDY OBJECTIVE: To examine the effect on large follicles (greater than or equal to 2 mm) of human menopausal gonadotropin (hMG) and buserelin acetate, a gonadotropin-releasing hormone agonist in monkeys. DESIGN: Experimental. SETTING: Reproductive research laboratory. ANIMALS: Fourteen cyclic cynomolgus monkeys receiving hMG alone for 8 days or buserelin acetate plus 8 (group 1), 12 (group 2), or 16 (group 3) days of hMG administration always starting from day 1 of the cycle. RESULTS: The different treatments were effective in over-riding the specific ovulatory quota of 1, and more large follicles developed in treatments involving long duration and higher doses of hMG. In buserelin acetate plus hMG treatments, the frequency of dissociated follicles and follicles in late atresia were, respectively, lower and higher than in hMG alone treatment. The numbers of recoverable mature oocytes (germinal vesicle breakdown) were similar to the numbers of such oocytes recovered after hyperstimulation performed for human in vitro fertilization and embryo transfer (IVF-ET). However, the number of mature oocytes enclosed in typically preovulatory follicles was very low because there were numerous dysmature follicles. CONCLUSION: These data suggest a deleterious effect of buserelin acetate plus hMG treatments on the recruitable follicles at the time when treatments start. The implications of these observations in the field of human IVF-ET are discussed. PMID- 1906018 TI - Growth hormone in serum of women during the menstrual cycle and during controlled ovarian hyperstimulation. AB - STUDY OBJECTIVE: To investigate the interrelationships between circulating levels of endogenous human growth hormone (hGH), gonadotropins, estradiol (E2), and progesterone (P). DESIGN: Retrospective. SETTING: Assisted reproductive technology center. PATIENTS: Nine normally cycling women from whom blood samples were drawn daily; 18 patients undergoing controlled ovarian hyperstimulation. RESULTS: During the menstrual cycle, average (+/-SE) hGH levels in serum ranged between 7.97 +/- 2.71 microIU/mL on day 11 and 2.11 +/- 0.38 microIU/mL on day 22. Serum hGH levels did not correlate with peripheral levels of follicle stimulating hormone (FSH), luteinizing hormone, P, or E2 and were related to the serum E2:FSH ratio (adhibited as an index of ovarian response to FSH) on cycle day 10 only. Levels of hGH in sera of patients undergoing controlled ovarian hyperstimulation were near 4 microIU/mL and were directly related to peripheral E2 levels at the time of induction of oocyte maturity. When corrected for differences in follicle number between stimulated patients, changes in serum E2 content were independent of respective hGH levels. CONCLUSION: The findings challenge speculation that endogenous peripheral hGH content might relate to ovarian responsiveness to FSH. PMID- 1906017 TI - Ovulatory dysfunction during continuous administration of low-dose levonorgestrel by subdermal implants. AB - OBJECTIVE: To study the endocrinologic profile of regularly menstruating users of levonorgestrel subdermal implants. DESIGN: Observational, prospective, case controlled comparative study. SETTING: The Family Planning Clinic of PROFAMILIA, in Santo Domingo, Dominican Republic. PATIENTS, PARTICIPANTS: Thirty one regularly cycling Norplant users and 12 nonhormonal contraceptors who volunteered to participate. INTERVENTIONS: Norplant contraceptive implants were inserted in 31 subjects between 13 and 77 months before this study. MAIN OUTCOME MEASURES: Follicle-stimulating hormone, luteinizing hormone, estradiol (E2), and progesterone (P) were serially assayed for one menstrual cycle. RESULTS: Almost half of the cycles among Norplant users were anovulatory; all the rest (55%) had some form of dysfunction: diminished gonadotropin surge, luteal phase insufficiency (low P levels and shortened luteal phase), and E2 profiles different from normal controls. CONCLUSIONS: Anovulation is clearly one of the main mechanisms of action of Norplant, but even in presumptive ovulatory cycles, the dysfunctions described possibly contribute to the high contraceptive effectiveness of Norplant. PMID- 1906019 TI - Avoidance of cancellation of potential hyperstimulation cycles by conversion to in vitro fertilization-embryo transfer. AB - OBJECTIVE: The study was undertaken to minimize the rate of ovarian hyperstimulation and to avoid cancellation of human treatment cycles in women treated with human menopausal gonadotropin (hMG) for induction of ovulation. SETTING: Patients were treated in the fertility clinic and in vitro fertilization unit of our institution, which is a government, university-affiliated hospital. PATIENTS: Ninety anovulatory patients were treated with hMG. Of these, 12 were at high risk for ovarian hyperstimulation. The criteria for potential ovarian hyperstimulation syndrome were rising excessive 17 beta-estradiol levels of greater than 1,500 pg/mL in the presence of multiple follicles with a mean diameter greater than 15 mm. These patients were transferred for continuation of treatment to our in vitro fertilization-embryo transfer (IVF-ET) unit. INTERVENTIONS: The patients underwent ova retrieval by the ultrasonically guided transvaginal approach. RESULTS: Of the 12 patients, 5 conceived (41.6%). Two patients had a mild ovarian hyperstimulation syndrome, and 1 had a moderate syndrome and was hospitalized for observation for 48 hours. CONCLUSION: In view of the results, we suggest that IVF-ET should be considered in cases in which ovarian hyperstimulation syndrome is imminent, rather than withhold human chorionic gonadotropin and cancelling the treatment cycle. PMID- 1906020 TI - The Lupron screening test: tailoring the use of leuprolide acetate in ovarian stimulation for in vitro fertilization. AB - STUDY OBJECTIVE: To evaluate the prognostic and therapeutic value of a Lupron (leuprolide acetate; Tap Pharmaceuticals, North Chicago, IL) screening test before ovarian stimulation for in vitro fertilization (IVF). DESIGN: Prospective. SETTING: Outpatient IVF program. PATIENTS: Eighty patients exhibited four early estradiol (E2) patterns. Patients with pattern A and B remained on a flare-up ovarian stimulation protocol. Patients with pattern C were randomized to three ovarian stimulation protocols. Patients with pattern D were treated with the flare-up protocol using a high pure follicle-stimulating hormone (FSH) dose. RESULTS: Patterns, A, B, C, and D occurred in 44%, 16%, 25%, and 15% of the patients, respectively. The E2 pattern recurred in 77% of subsequent IVF cycles. Pattern A and B patients achieved a 41% (23/56) and 22% (5/23) ongoing pregnancy rate (PR) per stimulated cycle. An early luteal phase Lupron protocol had the best ongoing PR per stimulated cycle (10/27, 37%) in patients with a pattern C response. Pattern D patients had a 20% (5/25) ongoing PR per stimulated cycle. CONCLUSION: The Lupron screening test allows prospective selection of stimulation protocols in ovulatory patients undergoing IVF. Early E2 patterns A and B should be treated with the flare-up protocol. Pattern C patients benefit from the luteal phase Lupron protocol and pattern D patients benefit from a high pure FSH flare up protocol. PMID- 1906021 TI - Relationship of follicle number, serum estradiol, and other factors to birth rate and multiparity in human menopausal gonadotropin-induced intrauterine insemination cycles. AB - OBJECTIVE: To determine the characteristics associated with pregnancy and multiple gestation after human menopausal gonadotropin intrauterine insemination (hMG-IUI). DESIGN: Prospective study of all patients undergoing hMG-IUI between January 1, 1984 and December 31, 1989. SETTING: University affiliated private clinic. PATIENTS: Four hundred twenty-four infertility patients undergoing 779 cycles of hMG-IUI. MAIN OUTCOME MEASURES: The relationship between estradiol (E2), number and size of follicles, age, and initial semen quality on pregnancy and multiple gestations in hMG-IUI cycles. RESULTS: The number of follicles greater than or equal to 12 mm was correlated with births and predicted all multiple births (r = 0.140, P less than 0.001). The corrected birth rate was 25.8% for age less than 35 and 14.0% for age greater than or equal to 35 when four or more follicles were greater than or equal to 12 mm. The uncorrected clinical pregnancy rate (PR) and birth rate were 12.8% and 10.5%, respectively. Decreased births were associated with tubal adhesions alone (P less than 0.03) or with endometriosis (P less than 0.002), more than four cycles of treatment (P = 0.01), initial sperm count less than 5 x 10(6) per mL (P less than 0.01), initial sperm motility less than 30% (P less than 0.002), and age greater than or equal to 35 (P less than 0.01). Estradiol was correlated with birth rate (r = 0.160, P less than 0.001), which increased from 3.6% when E2 was less than 500 pg/mL to 19.6% when E2 was greater than or equal to 2,500 pg/mL. CONCLUSIONS: The outcome of hMG-IUI is related to the number of follicles greater than or equal to 12 mm, to E2, and to age. Optimal PRs from hMG-IUI require mild ovarian hyperstimulation. PMID- 1906022 TI - Effects of Ca2+ and ionophore A23187 on protein synthesis in intact rabbit reticulocytes. AB - 1. Amino acid incorporation in intact rabbit reticulocytes was unaffected by depletion of Ca2+ with EGTA. 2. The Ca2+ ionophore A23187 strongly inhibited incorporation in reticulocytes incubated in 1 mM Ca2+ but not in EGTA. Polysomal profiles and average ribosomal transit times of cells treated with Ca2+ ionophore at 1 mM Ca2+ were characteristic of translational elongation block. 3. The behavior of reticulocytes with respect to Ca2+ and A23187 contrasts with that of nucleated cells possessing endoplasmic reticulum in which protein synthesis is inhibited at translational initiation by either Ca2+ depletion or by exposure to Ca2+ ionophore. PMID- 1906023 TI - The effect of aldose reductase inhibitors on glomerular prostaglandin production and urinary albumin excretion in experimental diabetes mellitus. AB - The effect of two structurally unrelated aldose reductase inhibitors, sorbinil and ponalrestat, on glomerular prostaglandin production and urinary albumin excretion was investigated in rats with diabetes induced by streptozotocin. It was found that both aldose reductase inhibitors, when administered from the time of induction of the diabetes, significantly decreased the raised urinary albumin excretion in the diabetic rats, although it remained elevated compared with non diabetic rats. Glomerular prostaglandin E and 6-keto-prostaglandin F1 alpha production was significantly increased in glomeruli obtained from the diabetic rats. Inhibition of aldose reductase caused a reduction in the raised glomerular prostaglandin production, although this remained above that observed in the non diabetic rats. Subsequent experiments were performed to determine whether the effects of the aldose reductase inhibitors could be explained by effects on glomerular filtration rate. It was found that ponalrestat, at a dose which markedly reduced urinary albumin excretion, did not significantly affect glomerular filtration rate in non-diabetic rats, rats with untreated streptozotocin-induced diabetes and rats with diabetes partially treated with low dose insulin. Glomerular sorbitol concentrations were significantly elevated in untreated diabetic rats as early as two weeks after the induction of diabetes. It is concluded that the administration of aldose reductase inhibitors from the time of induction of diabetes significantly reduces glomerular prostaglandin production and urinary albumin excretion. The latter effect is not due to an effect on glomerular filtration rate. Increased polyol pathway activity may account in part for the increased glomerular prostaglandin production and urinary albumin excretion in early experimental diabetes. PMID- 1906024 TI - Reduced glycogen synthase activity in skeletal muscle from obese patients with and without type 2 (non-insulin-dependent) diabetes mellitus. AB - In order to evaluate the importance of a defect in insulin mediated non-oxidative glucose metabolism and glycogen synthase activity in skeletal muscles in obese subjects with and without Type 2 (non-insulin-dependent) diabetes mellitus we studied: 10 lean and 10 obese control subjects and 12 obese diabetic patients using the euglycaemic hyperinsulinaemic clamp technique (basal, 20 mU.(m2)-1.min 1, 80 mU.(m2)-1.min-1) in combination with indirect calorimetry. Muscle biopsies were taken from m. vastus lateralis at each insulin level. We found that non oxidative glucose metabolism could be stimulated by insulin in all three groups (p less than 0.01). The values obtained at the highest insulin levels (around 140 microU/ml) were lower in both obese groups compared to the lean control subjects (118 +/- 21, 185 +/- 31, 249 +/- 14 mg.(m2)-1.min-1 (p less than 0.01]. Insulin stimulation of the glycogen synthase activity at a glucose-6-phosphate concentration of 0.1 mmol/l was absent in both obese groups, while activities increased significantly in the lean control subjects (19.6 +/- 4.2% to 45.6 +/- 6.8%, p less than 0.01). Glycogen synthase activities at the highest insulin concentrations only differed significantly between lean control subjects and obese diabetic patients (45 +/- 7% and 31 +/- 5%, p less than 0.05). We conclude that insulin resistance in peripheral tissues in obese subjects with and without Type 2 diabetes may be partly explained by a reduced insulin mediated non oxidative glucose metabolism and that this abnormality might be due to an absent insulin stimulation of glycogen synthase in skeletal muscles. This enzyme defect is correlated to obesity itself. PMID- 1906025 TI - Desmin expression in fibroblasts of murine periovular granuloma during liver Schistosoma mansoni infection. AB - We have studied the expression of the desmin gene, a muscle-specific intermediate filament protein in the granuloma cells of mouse liver infected with Schistosoma mansoni. In situ hybridization using a desmin DNA probe showed that fibroblastic cells in the granuloma strongly expressed desmin mRNAs, while in normal liver these cells did not express this mRNA to a detectable degree. The quantitative analysis of total RNAs demonstrated that the proportion of specific desmin mRNA increased from 14 to 18 weeks after infection and decreased at 20 weeks. The analysis of collagen gene expression indicated that the amount of type III collagen mRNAs was still increasing after 18 weeks from infection; in contrast, the amount of type I collagen mRNAs remained unchanged at that stage. A good correlation was observed between the detection of the specific mRNAs and the detection of both desmin and collagen molecules. Therefore, these data point to a coordinate induction of desmin and collagen gene expression during Schistosomal granuloma formation. They also suggest that the expression of the myofibroblast phenotype involves the induction of both genes. PMID- 1906026 TI - The decision to suggest screening lower gastrointestinal endoscopy: the effect of training. AB - Primary care residency directors in the Southeastern US were surveyed to obtain information on training in lower gastrointestinal endoscopy (LGIE). All residents in a sample of programs were asked to complete a similar questionnaire. Response was 77% for family practice residencies and 60% for internal medicine residencies. Significantly fewer (43%) internal medicine residents reported receiving training in either 35 cm or 60 cm LGIE than family practice residents (77%). When asked if they would suggest LGIE to screen an asymptomatic patient, 67% of family practice and 84% of internal medicine residents replied affirmatively. Those residents who had received training were significantly more likely to suggest screening LGIE. The screening decision was not influenced by the specialty of the physician who supervised the resident training. Out-of pocket cost to the patient was expected to be a major consideration in the screening decision, but this was not supported statistically. Greater availability of residency training in LGIE will likely increase its use in screening. PMID- 1906027 TI - Posttranslational cleavage of rat intestinal lactase occurs at the luminal side of the brush border membrane. AB - The intestinal sucrase-isomaltase precursor is cleaved at the brush border membrane by luminal proteases. Whether the lactase precursor also is cleaved by luminal proteases is uncertain. Lactase synthesis and processing was studied in 0 and 15-day-old rats after IP administration of [35S]methionine, and changes in precociously cortisone-induced sucrase-isomaltase were used as an internal control. Mucosal lactase and sucrase-isomaltase were separately immunoprecipitated and analyzed by autoradiography after electrophoresis. In both 0- and 15-day-old rats, mucosal lactase appeared as a 200K lactase precursor band at 30 minutes and as 200K and 225K lactase precursor bands at 60 minutes and was cleaved to form a 130K lactase band 120-240 minutes after labeling; sucrase isomaltase similarly appeared as 210K and 220K bands at 30-60 minutes and was cleaved to form 140K I and 120K S subunits by 240 minutes in day 15 rats. To determine the role of luminal proteases, intestinal segments were isolated in situ and the luminal contents were flushed 30 minutes after labeling. Unflushed segments were used as controls. Only lactase precursor and sucrase-isomaltase precursor were present 240 minutes after labeling in flushed intestinal segments, but lactase precursor and sucrase-isomaltase precursor were cleaved in unflushed segments. Addition of trypsin or elastase into the lumen of flushed segments resulted in partial cleavage of lactase precursor but not of sucrase-isomaltase precursor. Luminal contents collected from the small intestine of day 15 rats 120 and 240 minutes after labeling showed 35S-labeled 130K and 80K polypeptides in lactase immunoprecipitates. It is concluded that intestinal lactase is synthesized as lactase precursor and transported to brush border membrane and cleaved by luminal proteases, and the amino end polypeptide cleaved from lactase precursor is released into the lumen. PMID- 1906028 TI - Comparison of 1 or 3 MU of interferon alfa-2b and placebo in patients with chronic non-A, non-B hepatitis. AB - Ninety patients with histologically documented chronic non-A, non-B hepatitis were randomly allocated to receive SC injections of placebo or of 1 or 3 MU of recombinant interferon alfa-2b three times weekly for 24 weeks. Complete normalization of alanine aminotransferase levels occurred posttreatment in 43.3% of patients receiving 3 MU, in 20% of those receiving 1 MU, and in 6.7% of untreated patients (P less than 0.0005 vs. those treated with 3 MU). Alanine aminotransferase normalization was sustained for 6 months after therapy in 13.3% of the patients treated with 3 MU and in 3.3% of those given 1 MU or placebo. The decline of alanine aminotransferase levels following interferon therapy showed independent, positive correlations with female sex (P less than 0.03) and younger age (P less than 0.05). The Knodell's fibrosis score was strongly positively correlated with age (P less than 0.0001). It is concluded that 3 MU of interferon is a more effective dose than 1 MU for controlling disease activity in non-A, non B chronic hepatitis patients. Women and younger and noncirrhotic patients are more likely to respond. PMID- 1906029 TI - Antibiotic prophylaxis for prevention of spontaneous bacterial peritonitis? PMID- 1906030 TI - Nitroglycerin in the treatment of portal hypertension. PMID- 1906031 TI - Endoscopic management of gastric outlet obstruction. PMID- 1906032 TI - [Plasmapheresis in the treatment of cytostatic disease in patients with lymphogranulomatosis]. PMID- 1906033 TI - [Rational algorithm of primary Rhesus typing]. PMID- 1906034 TI - [An unified method of one-stage quantitative analysis of factors VIII and IX. I. (Results of the studies of the working group of the All-Union Problem-Solving Commission on "Pathology of hemostasis")]. PMID- 1906035 TI - Characterization of cDNAs encoding the polypyrimidine tract-binding protein. AB - The polypyrimidine tract of mammalian introns is recognized by a 62-kD protein (pPTB). Mutations in the polypyrimidine tract that reduce the binding of pPTB also reduce the efficiency of formation of the pre-spliceosome complex containing U2 snRNP. The PTB protein was purified to homogeneity by affinity chromatography on a matrix containing poly(U), and peptide sequence was used to isolate several cDNAs. Because a variety of cell types express mRNA complementary to these cDNAs, PTB may be a ubiquitous splicing factor. Three classes of cDNAs were identified, on the basis of the presence of additional sequences at an internal position. This variation in sequence probably reflects alternative splicing of the PTB pre mRNA and produces mRNAs encoding the prototype PTB protein, a form of PTB protein containing 19 additional residues, and a truncated form of PTB protein with a novel carboxyl terminus. A murine homolog of pPTB has been characterized previously as a DNA-binding protein. Sequence comparisons indicate that pPTB is distantly related to the hnRNP L protein and that these two proteins should be considered as members of a novel family of RNA-binding proteins. PMID- 1906036 TI - Characterization and molecular cloning of polypyrimidine tract-binding protein: a component of a complex necessary for pre-mRNA splicing. AB - alpha-Tropomyosin exons 2 and 3 are spliced in a mutually exclusive manner. Exon 3 is included as the default exon in the mRNA of most cell types, whereas exon 2 is only included in the mRNA of smooth muscle cells. The primary determinant for the default selection of exon 3 is the branchpoint/polypyrimidine tract. This element upstream of exon 3 clearly and effectively outcompetes the corresponding element upstream of exon 2. To identify trans-acting factors that bind to this important cis element, we used UV cross-linking to identify a 57-kD protein whose binding characteristics directly correlate with 3'-splice-site selection in cis competition splicing assays. This protein appears to be identical to polypyrimidine tract-binding protein. In this report we have used oligonucleotides derived from peptide sequences to isolate and sequence cDNA clones encoding this 57.2-kD protein. The primary sequence reveals a novel protein with significant homology to other RNA-binding proteins. Expression of the mRNA is detected in all tissues and cells examined, although its levels exhibit tissue-specific and developmental regulation. Using a biochemical complementation assay, we have found that this protein, along with a 100-kD protein, exists as part of a large complex that is required to rescue splicing from depleted nuclear extracts. PMID- 1906037 TI - [Functional state of experimental animals drinking water obtained by the method of hydration of carbon dioxide]. PMID- 1906038 TI - [Complex sanitary-microbiological criteria of evaluating the quality of water in increasing anthropogenic load]. AB - It has been established with the help of sanitary-hygienic, microbiological and statistical methods, that the increasing ++anthropogenic stress on water reservoirs induce quantitative and qualitative changes of water biocenosis under the conditions of intensive use of water reservoirs for economic purposes. It can produce unfavourable health effects on the population, as well as on the equilibrium of the local ecological microsystems. The necessity has been substantiated of the use of complex sanitary-microbiological criteria of the assessment of the quality of water objects to provide their epidemic safety, to preserve and rehabilitate the processes of ++self-purification of water under the conditions of technogenic exposures. PMID- 1906039 TI - [Activation of lipid peroxidation in the liver mitochondria and acute toxicity of chemical compounds]. AB - The effect of toxic substances on the functional state of liver mitochondria has been studied. It has been shown, that the contact of toxic substances with mitochondria lead to the reduction of the degree of association of oxidation with phosphorylation. EDTA in concentrations necessary to inhibit lipid peroxide oxidation prevents toxic effects. Preliminary antioxidant treatment of mitochondria prevents toxic damage of membranes. A close correlation has been established between chemical compounds toxicity and the concentration of antioxidants necessary for the prevention of toxic effects, as well as between chemical compounds toxicity and cumulation of malonic dialdehyde in mitochondria membranes. PMID- 1906040 TI - [Determining the level of lysine in the air]. PMID- 1906041 TI - [Levonorgestrel-releasing subcutaneous implants. First year's experience]. AB - This multicentric study was done in order to know the anticonceptive efficacy and side effects of subdermic implants liberating levonorgestrel, in Mexican women. Results analysis, at one year, of 246 women, at four medical centers of Mexican Institute of Social Security (IMSS), showed that this anticonceptive is highly efficacious, as there were no pregnancies in 2326 months of observation. The main side effects were: menstrual disorders in 34.8% of women; soreness in implantation site in 3.6%; headache in 13.4% and nausea, dizziness and vomiting in 11.6%. The most frequent causes for implant retirement were menstrual cycle alterations, and soreness at implantation site, with 7.3 and 3.5 respectively. The continuity rate at one year was 84.3, which was higher to what has been seen at the Institution with other temporal anticonceptive methods, so the implants may be considered as one more alternative in family planning methods. PMID- 1906042 TI - [Prophylactic use of antibiotics in cesarean section]. AB - The objective of this investigation was to determine the effectiveness of ampicillin administration as a prophylactic regime in patients undergoing cesarean section. A double blind randomized study compared a long course of ampicillin (7 days) to a short course of ampicillin (three doses) to placebo. Thirty one patients were included in the placebo group and sixty patients in the drug groups. Only one patient in the placebo group and one in the drug group developed infectious morbidity. There was no significant difference (p less than 0.001) between the placebo and ampicillin groups. PMID- 1906043 TI - [Endoscopic laser therapy. Indications, effectiveness and cost analysis in a medical department]. AB - Between June 1985 and December 1988, 297 endoscopic laser procedures were performed in 130 patients. The indications comprised hemostasis, coagulation of potentially bleeding lesions, palliative tumor therapy in the upper and lower gastrointestinal tract and in the tracheobronchial tree, eradication of adenomas after incomplete snare resection, and recanalization of benign esophageal/cardiac strictures and postoperative colonic stenoses. In addition, an endoscopically introduced biliary endoprosthesis was shortened. Treatment was highly effective, and the complication rate less than 1%. The average operating cost of the laser equipment was DM 80 per application, increasing to 430 DM when account was taken of the high purchasing price of the laser. PMID- 1906044 TI - Differences in the lectin-binding patterns of the periportal and perivenous endothelial domains in the liver sinusoids. AB - We have studied the distribution patterns of carbohydrate terminals on the endothelial surface of the mouse liver microvasculature. For this purpose, a wide battery of FITC lectins specific to glucose, mannose, galactose, fucose, N-acetyl neuraminic acid, N-acetyl-galactosamine and N-acetyl-glucosamine residues were incubated on liver cryostat sections or intraportally perfused under physiological conditions. All the resulting hepatic sections were examined under fluorescent microscopy and confocal laser scanning microscopy. With the exception of N-acetyl-galactosamine- and fucose-binding lectins, all the perfused lectins specifically bound to the microvascular wall as confirmed by blocking methods using their corresponding sugars. A wide range of binding was, however, observed among the lectins, and the latter were classified into four groups according to their affinities for the different segments of the hepatic microvasculature: (a) equal affinity for all segments (concanavalin A); (b) different affinities depending on acinar zone (wheat germ agglutinin, Ricinus communis toxin, phytohemagglutinin E, Erythrina cristagalli agglutinin and Pisum sativum agglutinin); (c) preferential binding to the sinusoidal network (Lathyrus odoratus, phytohemagglutinin); and (d) lectins that fail to bind to the hepatic microvasculature (N-acetyl-galactosamine- and fucose-binding lectins). Sinusoidal segment walls in acinar zone 1 expressed a higher concentration of certain lectin binding carbohydrate residues (N-acetyl-neuraminic acid, N-acetyl-galactosamine, galactose, mannose and glucose) than in acinar zone 3. The labeling patterns obtained through the incubation of liver sections or through in vivo perfusion with the different lectins did not always coincide. Only concanavalin A, wheat germ agglutinin and phytohemagglutinin E lectins proved to be concordant (i.e., they produced identical labeling patterns in both procedures).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1906045 TI - Purification of hepatocyte couplets by centrifugal elutriation. AB - An initial preparation of rat hepatocytes containing approximately 30% couplets was enriched by centrifugal elutriation. Of the couplets loaded onto the elutriator, 87% were eluted at medium flow rates of 60 to 80 ml/min at a rotor speed of 1,100 rpm; cells eluted in this range maintained a viability of more than 95%. Peak fractions were enriched in couplets to 84.5% +/- 2.5%. After elutriation, couplets retained the ability to secrete fluorescent cholephiles into sealed canalicular vacuoles. The preparation can now be used in hepatobiliary and hepatotoxicity studies not possible with preparations in which they are minor components. PMID- 1906046 TI - Thyrotropin-releasing hormone facilitates display of reproductive behavior and locomotor behavior in an amphibian. AB - In the amphibian brain, thyrotropin-releasing hormone (TRH) is present in many regions outside the hypothalamus. The functions of this extrahypothalamic TRH however are unknown. We sought to determine whether TRH or its metabolites altered reproductive behaviors (amplectic clasping behavior) or locomotor behaviors of the male South African clawed frog, Xenopus laevis. TRH-injected (100 micrograms; dorsal lymph sac injection) male Xenopus displayed significantly fewer amplectic clasp attempts and longer clasp durations than saline-injected controls. The TRH metabolites, TRH acid and histidylproline diketopiperazine, similarly altered clasping behavior. Several hormones released by TRH, including thyroid-stimulating hormone, melanocyte-stimulating hormone, prolactin, and dopamine, had no significant effect on clasp frequency or duration. Locomotor activity in Xenopus males was increased significantly after 15 min following TRH injection (150 micrograms); this effect persisted for at least 1 hr. The metabolites did not alter locomotion. These studies indicate that TRH can facilitate the display of two behaviors in the South African clawed frog. Effects of TRH on locomotor and reproductive behaviors thus appear in several vertebrate classes. These behavioral actions of TRH likely occur through different mechanisms or at different sites. PMID- 1906047 TI - Sequence of the variant thyroxine-binding globulin (TBG) in a Montreal family with partial TBG deficiency. AB - The variant thyroxine-binding globulin in a family from Montreal (TBG-M) has a reduced affinity for thyroxine, shows a slight cathodal shift on isoelectric focusing, and has an increased susceptibility to inactivation by heat and acid. We present the molecular basis for TBG-M, deduced by sequencing the entire 1245 bp coding regions and intron/exon junctions of the TBG gene of an affected hemizygous male. A single nucleotide substitution in the codon for amino acid 113 of the mature protein (GCC to CCC) was found, resulting in the replacement of alanine by proline. The mutation was confirmed by allele-specific amplification of genomic DNA from the propositus and three other affected family members. Since point mutations throughout the molecule have been shown to alter the properties of variant TBGs, and because amino acid substitutions with proline are known to impair stability and function of proteins, the replacement of alanine 113 by proline provides a logical explanation for the observed properties of TBG-M. PMID- 1906048 TI - The clinical phenotype of two patients with a complete deletion of the iduronate 2-sulphatase gene (mucopolysaccharidosis II--Hunter syndrome). AB - Two patients with a complete deletion of the iduronate-2-sulphatase (IDS) gene are described. In both patients, the resulting phenotype was that of very severe Hunter syndrome (mucopolysaccharidosis II). In addition, both had features not commonly seen in this disorder, e.g. early onset of seizures in one patient and ptosis in the other. It is speculated that loss of adjacent loci may contribute to the unusual findings and that the severe features present in both patients may represent contiguous gene syndromes. Further analysis of IDS cDNA from other patients with Hunter's syndrome may eventually enable phenotype to be predicted more accurately. PMID- 1906049 TI - Biological functions of the water-insoluble fraction of mouse seminal vesicle fluid. I. Suppression of the blastogenic response of lymphocytes. AB - The effects of the water-insoluble fraction of mouse seminal vesicle fluid (WIF SVF) on lymphocytes was investigated to clarify its role in reproductive immunity. WIF-SVF inhibited the blastogenic response of T-cells to concanavalin-A (Con-A), but it did not inhibit the blastogenic response of B-cells to lipopolysaccharide (LPS). Pretreatment of splenocytes with WIF-SVF did not suppress the blastogenic response of splenocytes to Con-A when treated cells were washed prior to culture. WIF-SVF did not inhibit the proliferation of Con-A activated splenocytes, the response of listeria-immune splenocytes to listerial antigen, or the proliferation of IL 2-dependent HT-2 cells, or the growth of tumour cells (Yac 1 cells, Ehrlich ascites carcinoma cells, EL-4 cells). A listerial antigen-specific immune response was not induced after mice were immunized with both listerial antigen and WIF-SVF. WIF-SVF is mainly composed of protein and its suppressive activity was enhanced by heating at 100 degrees C. These results suggest that WIF-SVF inhibits the responsiveness of T-cells to antigens or mitogens non-specifically at the initial stage. PMID- 1906050 TI - Molecular analysis of MHC-class-I alterations in human tumor cell lines. AB - Molecular characterization of HLA-class-I expression was investigated in human tumor cell lines at the protein and mRNA levels using locus-specific monoclonal antibodies (MAbs) and probes. Some cell lines exhibited a differential expression of HLA-A and HLA-B products and also showed differences in the inducibility of HLA-class-I genes by gamma-IFN. Thus, gamma-IFN stimulation induced predominantly HLA-B mRNA in the HeP-2 cell line, which showed imbalances in basal levels of HLA A and HLA-B expression. This unequal inducibility of HLA genes may imply that locus-specific regulatory mechanisms are involved in the expression of individual HLA products. The specific mechanism controlling the differential expression of HLA subsets appears to be independent of c-myc activity. Northern blot analysis found no relationship between c-myc mRNA levels and specific mRNA for HLA-A and HLA-B antigens. PMID- 1906051 TI - DNA binding of regulatory factors interacting with MHC-class-I gene enhancer correlates with MHC-class-I transcriptional level in class-I-defective cell lines. AB - Tumor cells frequently show a lack of surface class-I major histocompatibility complex (MHC) antigen expression. These molecules are key recognition structures for immune rejection of tumor cells and their absence at the surface of tumor cells could favor the progression of tumors. We have analyzed the transcriptional mechanisms that could lead to suppression of MHC-class-I expression in human tumor cell K562. The expression of MHC-class-I genes is highly controlled by regulatory factors interacting with an enhancer sequence upstream of MHC-class-I genes. In this report we show that DNA binding activity of 2 regulatory factors, KBFI and NF-kappa B, known to be essential for constitutive expression of MHC class-I genes, is deficient in nuclear extracts from K562 cells. Induction of class-I gene expression at the surface of tumor cells by interferon-gamma (IFN gamma) and tumor necrosis factor alpha (TNF-alpha) shows that TNF-alpha can act in synergy with IFN-gamma to induce DNA binding of both factors NF-kappa B and KBFI to the class-I gene enhancer and that this induction of transcriptional factors is correlated with enhancement of MHC-class-I mRNA transcription and cell surface antigen expression. PMID- 1906052 TI - Organization of the human HLA-class-II region. AB - A detailed map of the class-II region of the human MHC has been established by pulsed-field-gel-electrophoresis (PFGE) mapping and cloning in yeast-artificial chromosome (YAC) vectors. The map revealed CpG islands, which are frequently associated with genes, in the gaps between the known HLA-class-II genes. Using cosmid walking and chromosome jumping, we have cloned 3 of these islands and have identified 5 novel genes, named RINGI-5. This brief report summarizes our present knowledge of these genes. PMID- 1906053 TI - Cell lineage-specific and developmental stage-specific controls of MHC class-II antigen expression. AB - In this report we present evidence and we review data from our laboratory which indicate the genetic complexity of regulatory mechanisms controlling MHC class-II gene expression. The MHC class-II genes can be expressed in 2 ways: in a constitutive fashion, as in B cells, and in an inducible fashion, as in macrophages, endothelial cells and certain tumors. In both cases the regulatory controls are mainly exerted at transcriptional level as a result of interactions between cis-acting regulatory DNA elements and trans-acting factors. The constitutive class-II-gene expression in B cells is under the control of developmentally regulated trans-acting factors with activator function and encoded by a series of genes, the AIR genes, one of which has been mapped in the mouse on chromosome 16. Interestingly, these regulatory mechanisms are conserved across species for at least 70 million years, because murine AIR-gene products can complement AIR gene defects of human B-cell mutants. The constitutive B-cell phenotype behaves as a dominant trait up to the plasma cell stage in which class II-gene expression is lost because of the activation of suppressor factors which repress transcription and which, in turn, behave as a dominant trait in somatic cell hybrids between B cells and plasma cells. Thus positive and negative signals regulating class-II-gene expression may behave as dominant or recessive traits, depending upon the particular developmental stage of the cell in which they operate. The mechanisms controlling class-II expression in inducible cells are distinct from those mediating constitutive expression. Indeed, induction of these genes is not sufficient to complement AIR-gene defects in hybrids between macrophages and class-II-negative mutant B cells. In contrast, constitutive expression is dominant in hybrids between class-II-positive B cells and macrophages, suggesting that in uninduced cells class-II-gene activation does not take place more because of lack of activator factors than because of the presence of constitutive transcriptional suppressors. On the basis of these results, we propose a model for developmentally controlled MHC class-II-gene expression during ontogeny. PMID- 1906054 TI - Immunization by gamma-IFN-treated B16-F10.9 melanoma cells protects against metastatic spread of the parental tumor. AB - B16-F10.9 is a highly metastatic clone of the B16-F10 melanoma line, that expresses low levels of MHC class-I antigens. F10.9 cells transfected with H-2Kb are highly immunogenic and consequently exhibit a low metastatic phenotype. Treatment with gamma-IFN elevated H-2Kb and H-2Db cell surface expression of F10.9 cells to levels much higher than did transfection of these genes. Yet, following intravenous injection, the gamma-IFN treated cells generated high loads of lung metastases. However, when tested for their immunogenic effect, they elicited CTL and were sensitive to CTL. Immunization with both the positive transfectant KI and the gamma-IFN-treated F10.9 cells protected in vivo against metastatic spread of a subsequent transplant of parental F10.9 cells. The protection elicited by KI transfectants was more effective than the protection by gamma-IFN-treated cells. PMID- 1906055 TI - Tumor-specific immunity can be enhanced by transfection of tumor cells with syngeneic MHC-class-II genes or allogeneic MHC-class-I genes. AB - Mouse Sal sarcoma cells are lethal in the autologous A/J (KkDd) host. In order to improve the immune response to the Sal tumor, Sal cells have been transfected with syngeneic MHC-class-II or allogeneic MHC-class-I genes. MHC-class-II transfectants are uniformly rejected by the autologous host and immunization with them protects against subsequent Sal challenge. The improved immunity is probably the result of enhanced generation of tumor-specific Th cells. We hypothesize that class-II tumor cells trigger an improved Th-cell response because they directly present Sal tumor antigens in the context of class-II molecules to Th cells, by passing professional APC. Studies by others have demonstrated that antigen presentation requires an intracellular signal transmitted by the cytoplasmic domain of the APC class-II molecule. Sal cells expressing class-II antigens with truncated cytoplasmic domains are as malignant as wild-type Sal cells. These experiments therefore support the role of tumor-cell class-II molecules as antigen presentation elements, and demonstrate the requirement for intact class II molecules for tumor protection. Sal cells have also been transfected with allogeneic MHC-class-I genes. Although Kb-transfected cells are not rejected by A/J mice, Db-transfected Sal cells and Kb- plus Db-transfected cells are rejected. The Db transfectants effectively immunize A/J mice against subsequent Sal challenge. These experiments demonstrate that expression of certain allogeneic MHC-class-I genes can lead to tumor-specific immunity, and that such transfectants can protect against challenges of wild-type tumor cells. Transfection of tumor cells with syngeneic MHC-class-II or allogeneic MHC-class-I genes may therefore be a potential strategy for improving tumor-specific immunity in the autologous host. PMID- 1906056 TI - Class-I MHC expression in the mouse lung carcinoma, line 1: a model for class-I inducible tumors. AB - We have examined the expression and biological effects of class-I MHC molecules on the immune response to the line I lung carcinoma. The line I system is of interest because these tumor cells have very low constitutive levels of class-I molecules but can be induced to express levels found on spleen cells, by culturing the cells with agents such as dimethylsulfoxide (DMSO) or interferon gamma (IFN-gamma). This induction is significant immunologically, since induced cells can be lysed very effectively by cytotoxic T lymphocytes (CTL), whereas the uninduced cells cannot. CTL clones that are reactive with line I cells have been generated and used in vitro and in vivo, to examine the interactions of T cells with line I. We have shown that the expression of class I on tumor cells is induced in vivo by IFN-gamma, and that this induction is associated with the ability to reject the tumor. We will also introduce preliminary data concerning the mechanism of induction in which CTL appear to induce class-I MHC both in vitro and in vivo. The results are discussed in terms of a model which may be important generally for class-I inducible tumors. PMID- 1906057 TI - The postictal psychosis of epilepsy: investigation in two patients. AB - Patients with epilepsy have a higher incidence of psychosis. Epilepsy-related psychotic behaviors include a chronic interictal schizophreniform illness, an "alternating psychosis" which remits with seizure activity, and ictal or perictal psychotic behaviors. In addition, there is an uncommon and less understood psychosis characterized by brief psychotic episodes during the postictal period. This report describes two patients with postictal psychosis and correlates their behavior with the pattern of seizures, electroencephalographic discharges, and anticonvulsant and psychotropic medications. The findings suggest that postictal psychosis results from increased epileptiform activity and continued cerebral dysrhythmia, has a latency in onset and is not due to the immediate postictal delirium, and reflects an exacerbation of underlying psychopathological tendencies. This report further discusses the potential pathophysiological mechanisms and management of this disorder. PMID- 1906058 TI - Effect of vitamin E and fat source in sows' diets on immune response of suckling and weaned piglets. AB - Thirty-six 7-mo-old gilts were used to study the effects of dietary vitamin E and fat source (5% sunflower oil or animal fat) in pregnant and lactating sow diets on serum vitamin E concentration and on cell-mediated and humoral immune response in suckling and weaned piglets. Six gilts each received one of six diets throughout pregnancy and lactation. The basal diets (13 mg alpha-tocopherol/kg diet) were supplemented with dl-alpha-tocopheryl acetate to 48 and 136 mg alpha tocopherol/kg of feed (average analyzed values). After weaning (at 4 wk of age) all pigs received identical diets (20 mg of alpha-tocopherol/kg feed). One week after weaning, pigs were immunized (i.m. with ovalbumin and tetanus toxoid) and antibody production was measured. Blood samples were taken immediately after birth, at 1 wk after birth, at weaning, and at four weekly intervals after weaning. Samples were analyzed for alpha-tocopherol concentration, total number of leukocytes, T- and B-lymphocytes, lymphocyte stimulation with concanavalin A, lysozyme activity, and immunoglobulin concentrations. It was concluded that a high vitamin E level in the sow's diet increased serum vitamin E concentration of 1-wk-old pigs (P less than .05). Immune response against ovalbumin was increased (P less than .05) at 1 wk of age after immunization for weaned pigs from sows fed the high level of vitamin E. Also, the phagocytic measures of pigs at 1 wk of age were increased by the medium vitamin E level (P less than .05). Fat sources in the sow's diet had no consistent effect on the immunological measures of pigs. PMID- 1906059 TI - Growth performance of weanling pigs fed corn-soybean meal diets with or without dried whey at various L-lysine.HCl levels. AB - A total of 490 crossbred weanling pigs were used to evaluate the responses to and the subsequent interaction between dietary dried whey and crystalline L lysine.HCl on postweanling growth and feed efficiency at two periods postweaning. The experiment was conducted as a 2 x 5 factorial arrangement of treatments in a randomized complete block design to evaluate two levels of edible-grade dried whey (0 or 25%) and five dietary lysine levels ranging from 1.10 to 1.50% in .10% increments using a corn-soybean meal mixture as the basal feedstuff. Pigs were allotted by weight, litter, and sex to seven replicates at weaning (23 +/- 2 d) and fed their treatment diets for a 35-d period. Daily gain and feed intake were greater (P less than .01) for both the 0- to 21- and the 22- to 35-d periods when dried whey was fed; the relative magnitude of the response to dried whey was greatest during the initial 21-d period. Growth responses during the 0- to 21-d period were, however, independent of dietary lysine level, suggesting that dietary lysine at a level of 1.10% is not the limiting nutrient in a corn-soybean meal diet or a corn-soybean meal diet with dried whey. From 22 to 35 d postweaning a linear growth response to lysine level occurred when the dried whey diet was fed, but no response was detected when lysine was added to the corn soybean diet, resulting in a diet x lysine level interaction (P less than .10).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1906060 TI - Expression of ClpB, an analog of the ATP-dependent protease regulatory subunit in Escherichia coli, is controlled by a heat shock sigma factor (sigma 32). AB - Escherichia coli K-12 produces at least two ATP-dependent proteases, Lon (La) and Clp (Ti), the latter consisting of a regulatory subunit (ClpA) and a proteolytic subunit (ClpP). The gene clpB encoding an analog of ClpA had been found at 57 min on the E. coli chromosome. Cloning and examination of novel heat shock promoters led us to identify a major clpB promoter specifically controlled by a heat shock sigma factor, sigma 32 (the rpoH [= htpR] gene product). beta-Galactosidase synthesis from a PclpB-lacZ operon fusion was transiently induced upon temperature shift from 30 to 42 degrees C, and the induction depended on the rpoH function. Chromosomal clpB transcripts also increased upon temperature upshift and were totally absent in the rpoH deletion strain. In the in vitro transcription experiments, the clpB promoter was specifically recognized and transcribed by RNA polymerase-sigma 32. Nucleotide sequencing and determination of mRNA start sites permitted us to identify a major heat shock promoter located upstream of the clpB coding sequence. The results clearly indicate that clpB expression is under direct control of sigma 32. Since ClpP was recently shown to be a sigma 32-dependent heat shock protein, the present finding suggests the possibility that a potential ATP-dependent protease, ClpB-ClpP complex, plays an important role against thermal stress in E. coli. PMID- 1906061 TI - In vivo genetic exchange of a functional domain from a type II A methylase between lactococcal plasmid pTR2030 and a virulent bacteriophage. AB - The conjugative plasmid pTR2030 confers bacteriophage resistance to lactococci by two independent mechanisms, an abortive infection mechanism (Hsp+) and a restriction and modification system (R+/M+). pTR2030 transconjugants of lactococcal strains are used in the dairy industry to prolong the usefulness of mesophilic starter cultures. One bacteriophage which has emerged against a pTR2030 transconjugant is not susceptible to either of the two defense systems encoded by the plasmid. Phage nck202.50 (phi 50) is completely resistant to restriction by pTR2030. A region of homology between pTR2030 and phi 50 was subcloned, physically mapped, and sequenced. A region of 1,273 bp was identical in both plasmid and phage, suggesting that the fragment had recently been transferred between the two genomes. Sequence analysis confirmed that the transferred region encoded greater than 55% of the amino domain of the structural gene for a type II methylase designated LlaI. The LlaI gene is 1,869 bp in length and shows organizational similarities to the type II A methylase FokI. In addition to the amino domain, upstream sequences, possibly containing the expression signals, were present on the phage genome. The phage phi 50 fragment containing the methylase amino domain, designated LlaPI, when cloned onto the shuttle vector pSA3 was capable of modifying another phage genome in trans. This is the first report of the genetic exchange between a bacterium and a phage which confers a selective advantage on the phage. Definition of the LlaI system on pTR2030 provides the first evidence that type II systems contribute to restriction and modification phenotypes during host-dependent replication of phages in lactococci. PMID- 1906062 TI - Cloning of pectate lyase gene pel from Pseudomonas fluorescens and detection of sequences homologous to pel in Pseudomonas viridiflava and Pseudomonas putida. AB - Pectate lyase (PL) depolymerizes pectin and other polygalacturonates (PGAs) and is thought to play a role in bacterial invasion of plants. Production of PL by the soft-rotting pathogen Pseudomonas fluorescens CY091 is regulated by Ca2+. In the presence of Ca2+, this bacterium constitutively synthesizes PL in media containing glucose, glycerol, or PGA and excretes over 87% of total PL into culture fluids. In the absence of Ca2+, the organism fails to use PGA as a carbon source and produces very low levels of PL in media containing glucose or glycerol. Of the small amount of PL produced by the bacterium in Ca(2+)-deficient media, over 78% was detected within the cells, indicating that Ca2+ is critical not only for the production but also for the secretion of PL. The pel gene, encoding an alkaline PL (pI 10.0, Mr 41,000) was cloned and located on the overlapping region of a 4.3-kb SalI and a 7.1-kb EcoRI fragment. The 7.1-kb EcoRI fragment appears to contain a promoter for pel gene expression. A 1.7-kb SalI XhoI subfragment of the 4.3-kb SalI fragment was cloned into pUC18 to give pROTM2. Escherichia coli cells carrying pROTM2 produce 50 to 100 times more PL than do cells carrying other pectolytic constructs. Production of PL by E. coli (pROTM2) was not affected by carbon sources or by Ca2+. The pI and Mr of PL from E. coli corresponded to values for its counterpart from P. fluorescens. A 0.7-kb BglII-ClaI fragment encoding the pel structural sequence was used to detect pel homologs in various species of fluorescent pseudomonads. Homologous sequences were observed in 10 of 11 strains of P. fluorescens, P. viridiflava, and P. putida. The pel gene in fluorescent pseudomonads is well conserved and may exist and remain repressed in certain strains or species which exhibit nonpectolytic phenotypes under laboratory conditions. PMID- 1906063 TI - The gene encoding dinitrogenase reductase 2 is required for expression of the second alternative nitrogenase from Azotobacter vinelandii. AB - Under diazotrophic conditions in the absence of molybdenum (Mo) and vanadium (V), Azotobacter vinelandii reduces N2 to NH4+ by using nitrogenase 3 (encoded by anfHDGK). However, dinitrogenase reductase 2 (encoded by vnfH) is also expressed under these conditions even though this protein is a component of the V containing alternative nitrogenase. Mutant strains that lack dinitrogenase reductase 2 (VnfH-) grow slower than the wild-type strain in N-free, Mo-, and V deficient medium. In this medium, these strains synthesize dinitrogenase reductase 1 (a component of the Mo-containing nitrogenase encoded by nifH), even though this component is not normally synthesized in the absence of Mo. Strains that lack both dinitrogenase reductases 1 and 2 (NifH-VnfH-) are unable to grow diazotrophically in Mo- and V-deficient medium. In this medium, NifH- VnfH- strains containing an anfH-lacZ transcriptional fusion exhibited less than 3% of the beta-galactosidase activity observed in the wild type with the same fusion. Beta-Galactosidase activity expressed by VnfH- mutants containing the anfH-lacZ fusion ranged between 57 and 78% of that expressed by the wild type containing the same fusion. Thus, expression of dinitrogenase reductase 2 seems to be required for transcription of the anfHDGK operon, although, in VnfH-mutants, dinitrogenase reductase 1 appears to serve this function. Active dinitrogenase reductase 1 or 2 is probably required for this function since a nifM deletion mutant containing the anfH-lacZ fusion was unable to synthesize beta galactosidase above background levels. An anfA deletion strain containing the anfH-lacZ fusion exhibited beta-galactosidase activity at 16% of that of the wild type containing the same fusion. However, in the presence of NH4+, the beta galactosidase activity expressed by this strain more than doubled. This indicates that AnfA is required not only for normal levels of anfHDGK transcription but also for NH4+ -and, to a lesser extent, Mo-mediated repression of this transcription. PMID- 1906064 TI - Stationary-phase-inducible "gearbox" promoters: differential effects of katF mutations and role of sigma 70. AB - Many of the changes in gene expression observed when Escherichia coli cells enter stationary phase are regulated at the level of transcription initiation. A group of stationary-phase-inducible promoters, known as "gearbox" promoter, display a characteristic sequence in the -10 region which differs greatly from the consensus sequence for sigma 70-dependent promoters. Here we describe our studies on the gearbox promoters bolAp1 and mcbAp, responsible for the temporally regulated transcription of bolA and the genes involved in the synthesis of the peptide antibiotic microcin B17, respectively. Deletion analysis of mcbAp demonstrated that the stationary-phase-inducible properties of this promoter are found in a DNA fragment extending from -54 to +11 bp, surrounding the transcriptional start site, and are separable from DNA sequences responsible for the OmpR-dependent stimulation of transcription of mcbAp. In vitro transcription studies indicate that the RNA polymerase holoenzyme involved in the transcription of mcbAp contains sigma 70. In this and an accompanying paper (R. Lange and R. Hengge-Aronis, J. Bacteriol. 173: 4474-4481, 1991), experiments are described which show that the product of katF, a global regulator of stationary-phase gene expression and a putative sigma factor, is required for the expression of bolAp1 fused to the reporter gene lacZ. In contrast, mcbAp appears to be negatively regulated by katF. We discuss the implications of these results for postexponential gene expression and the role of gearbox sequences in the regulation of promoter activity. PMID- 1906065 TI - A functionally split pathway for lysine synthesis in Corynebacterium glutamicium. AB - Three different pathways of D,L-diaminopimelate and L-lysine synthesis are known in procaryotes. Determinations of the corresponding enzyme activities in Escherichia coli, Bacillus subtilis, and Bacillus sphaericus verified the fact that in each of these bacteria only one of the possible pathways operates. However, in Corynebacterium glutamicum activities are present which allow in principle the use of the dehydrogenase variant and succinylase variant of lysine synthesis together. Applying gene-directed mutagenesis, various C. glutamicum strains were constructed with interrupted ddh gene. These mutants have an inactive dehydrogenase pathway but are still prototrophic, which is proof that the succinylase pathway of D,L-diaminopimelate synthesis can be utilized. In strains with an increased flow of precursors to D,L-diaminopimelate, however, the inactivation of the dehydrogenase pathway resulted in a reduced formation of lysine, with concomitant accumulation of N-succinyl-diaminopimelate in the cytosol up to a concentration of 25 mM. These data show (i) that both pathways can operate in C. glutamicum for D,L-diaminopimelate and L-lysine synthesis, (ii) that the dehydrogenase pathway is not essential, and (iii) that the dehydrogenase pathway is a prerequisite for handling an increased flow of metabolites to D,L diaminopimelate. PMID- 1906066 TI - Lactococcal proteinase maturation protein PrtM is a lipoprotein. AB - The production of enzymatically active proteinase by lactococci requires the joint presence of a proteinase gene, prtP, and a gene encoding a maturation protein, prtM. A 32-kDa protein produced by Escherichia coli upon expression of the prtM gene under the direction of the T7 RNA polymerase promoter was purified and used to obtain PrtM-specific antibodies. With these antibodies, immunogold labeling of lactococcal cells revealed that PrtM was associated with the lactococcal cell envelope. Western blot (immunoblot) analysis of whole lactococcal cells and isolated membrane vesicles indicated that PrtM was a membrane-associated protein. Radiolabeling of Lactococcus lactis with [3H]palmitic acid showed that PrtM was a lipoprotein. Partial secretion of PrtM into the culture medium was observed after Cys-24, the target residue for lipid modification, was replaced by an Ala residue by means of site-directed mutagenesis. This mutation did not affect proteinase activity. PMID- 1906067 TI - A dominant interfering mutation (CYR3) of the Saccharomyces cerevisiae RAS2 gene. AB - The dominant cyclic AMP-requiring mutation CYR3 had been previously reported as a mutation in the regulatory subunit of cyclic AMP-dependent protein kinase. However, recharacterization revealed that the CYR3 mutation was a nonconditional dominant lethal mutation and was a missense allele of RAS2 which results from the substitution of aspartic acid for glycine at amino acid 22. PMID- 1906068 TI - Proteoglycan and glycosaminoglycan synthesis by cultured rat mesangial cells. AB - The synthesis of metabolically labeled proteoglycans and glycosaminoglycans from medium, cell layer and substrate attached material by rat glomerular mesangial cells in culture was characterized. The cellular localization of the labeled proteoglycans and glycosaminoglycans was determined by treating the cells with Flavobacterial heparinase. Of the total sulfated glycosaminoglycans, 33% were heparan sulfate; 55% of the cell layer material was heparan sulfate; 80% of sulfated proteins in the medium were chondroitin sulfate/dermatan sulfate. Putative glycosaminoglycan free chains of heparan sulfate and chondroitin sulfate were found in both the medium and cell layer; 95% of total proteoglycans and most (90%) of the putative heparan sulfate free chains were removed from the cell layer by the heparinase, whereas only 50% of the chondroitin sulfate and 25% of dermatan sulfate were removed. Large amounts of hyaluronic acid labeled with 3H glucosamine were found in the cell layer. In summary, approximately 60% of total sulfated glycoproteins was in the form of putative glycosaminoglycan free chains. Thus rat mesangial cells may synthesize large amounts of putative glycosaminoglycan free chains, which may have biological functions in the glomerulus independent of proteoglycans. PMID- 1906069 TI - [The alteration of eicosanoid levels in arterial blood and its relation to the pathologic status of acute myocardial infarction]. AB - The role of arachidonic acid in patients with acute myocardial infarction (AMI) was investigated. Plasma levels of thromboxane (TX) B2, 6-keto-prostaglandin F1 alpha (6KPG), leukotriene (LT) B4, LTC4, peptideLTs (LTC4 + LTD4 + LTE4) were evaluated in 19 AMI patients, 2 unstable angina (UA) patients and 12 normal controls. Blood samples were obtained from the femoral and pulmonary arteries. Further, plasma levels of LTC4 from the antecubital vein were determined in 14 AMI patients on admission and 10 healthy volunteers. Plasma levels of TXB2, LTB4, LTC4, peptideLTs from arterial blood significantly increased in AMI patients at the acute stage and one day after an attack of AMI compared with those of normal controls. TXB2, LTB4, LTC4, peptideLTs levels in UA patients were higher than those of normal controls. TXB2, LTC4 and peptideLTs levels on week after an attack of AMI significantly decreased compared with those at the acute stage, and these values decreased to normal control levels one month after an attack of AMI. LTB4 levels did not decrease one week after an attack of AMI but they significantly decreased one month after an attack compared with those at the acute stage. These values from the pulmonary artery were not significantly different from the values from the femoral artery obtained at the equivalent phases. Plasma levels of 6KPG did not show significant serial changes either. But the patients showing high levels of 6KPG in the acute stage showed lower levels of CPK and lower Wanger's QRS score than the patients showing low levels of 6KPG. Plasma LTC4 levels in the venous blood of 14 AMI patients were also significantly higher than those of healthy volunteers. Serum levels of lipid peroxide, alpha tocopherol and superoxide dismutase activity were also measured but did not show significant serial changes in AMI patients. These results in AMI patients suggest that LTB4, LTC4 and peptideLTs, which are lipoxygenase metabolites of arachidonic acid, play an important role in the pathogenesis of AMI attacks as well as TXB2 and 6KPG, which are cyclooxygenase metabolites of arachidonic acid. PMID- 1906070 TI - Interferon-beta specifically inhibits interferon-gamma-induced class II major histocompatibility complex gene transcription in a human astrocytoma cell line. AB - We established cultures of human astrocytes and astrocytoma cells from surgical specimens, to study regulation of class II major histocompatibility (MHC) complex antigen expression by interferons. Using these cultures we previously showed that expression of the class II MHC determinant HLA-DR could be induced by interferon gamma and this induction was inhibited by interferon-beta. In this report, we extend these observations by showing that the inhibitory effect of interferon beta on interferon-gamma induction of the class II MHC gene HLA-DR alpha was exerted at the transcriptional level, as documented by nuclear run-on experiments and confirmed with blot hybridization analysis. Astrocyte expression of intercellular adhesion molecule-1 (ICAM-1) was induced efficiently by interferon gamma, but not by interferon-beta, and induction of ICAM-1 expression by interferon-gamma could not be impaired by interferon-beta, suggesting that the suppressive effect on induction of HLA-DR was relatively gene-specific. Furthermore, interferon-beta did not antagonize interferon-gamma induction of HLA DR expression in human monocytes, suggesting that the inhibition observed in astrocytes was relatively tissue-specific. PMID- 1906071 TI - Immunoturbidimetric assay for estimating free light chains of immunoglobulins in urine and serum. AB - An immunoturbidimetric assay for the assessment of free kappa and lambda light chains of immunoglobulins was developed using a commercial polyclonal antiserum with reactivity towards epitopes on the light chains, which are not expressed when they are bound to heavy chains. The assay, on a centrifugal analyser, is simple and rapid. The limit of detection is 5 mg/l of free light chain, with an assay range of 5-120 mg/l, intrabatch precisions from 1.5-6.4%, and interbatch precisions from 6.5-8.9%. The assay was only slightly less sensitive than colloidal gold staining of cellulose acetate electrophoreses for the detection of Bence-Jones protein in urine. For the serial monitoring of response to chemotherapy in patients with myeloma, the assay correlated well with serum paraprotein estimates obtained by densitometric scanning of Ponceau stained cellulose acetate electrophoreses, but not with serum beta-2 microglobulin measurements, even after correction for the effects of creatinine. These assays may prove to be of use for the monitoring of tumour response in the treatment of Bence-Jones myeloma. PMID- 1906072 TI - Exaggerated and prolonged thyrotrophin releasing hormone (TRH) test responses in tertiary hypothyroidism. AB - A 60 year old man with panhypopituitarism due to a large meningioma and prolonged and exaggerated thyroid stimulating hormone (TSH) responses is described. Initial investigations showed a subnormal urinary free cortisol concentration, a low serum cortisol taken at 0900 hours, and a low free T4 concentration. The TSH was towards the upper end of the normal range. Subsequently pituitary function tests showed subnormal production of luteinising hormone in response to luteinising hormone releasing hormone (LHRH) and a short synacthen test with a low 30 minute cortisol value. Long synacthen testing showed a normal response at four days, confirming that the abnormalities were due to a pituitary or hypothalamic cause. A computed tomogram showed a large meningioma compressing the hypothalamus, pituitary, and temporal lobe. TRH testing showed a prolonged and exaggerated response, consistent with tertiary hypothyroidism. PMID- 1906073 TI - Practice guidelines and malpractice litigation: collision or cohesion? AB - Practice guidelines are standardized specifications for managing particular clinical problems and are intended to improve the outcomes of medical care by increasing adherence to standards of care. They are also meant to make medicine more cost-effective by eliminating unnecessary procedures. A relatively recent phenomenon, the practice guidelines now emerging will have implications for malpractice, which also intends to bring about better care. They will probably not revolutionize the procedures that courts use to determine negligence, but judges will integrate guidelines into their decision-making process. This development should be welcomed. Guidelines should prove to be useful as either inculpatory or exculpatory evidence of negligence. They are unlikely to generate much new litigation, although there is some potential for suits against those who issue guidelines, especially if guidelines are not revised as the technology of medical care changes. PMID- 1906074 TI - Cell kinetics of gastrointestinal tumors after different nutritional regimens. A preliminary report. AB - Forty-four cases of different untreated gastrointestinal tumors were studied with regard to cell kinetic activity. As a pilot experiment, we also determined the 3H TdR Labeling Index (LI) in 28 patients in basal conditions and after 15 days of nutritional manipulation with prevalently lipid-based or glucose-based feeding to ascertain whether selective nutritional regimens could affect tumor proliferation. Preliminary results from this study indicate that a kinetic perturbation is induced in tumor cells by nutritional manipulation. Lipid-based feeding seems to produce effects similar to those of chemical or physical anticancer agents, thus suggesting a possible supporting role of nutritional manipulation in cancer treatment strategy. PMID- 1906075 TI - The consensus workshops for the detection of autoantibodies to intracellular antigens in rheumatic diseases. AB - In 1988 and in 1989 consensus workshops were organized in order to define the interlaboratory concordance in detecting autoantibody specificities in selected sera from patients with rheumatoid disorders and to determine the possible causes of discrepancies. In total 20 sera were tested for the presence of antibodies against nRNP, Sm, Ro (SS-A), La (SS-B), Scl-70, centromeric antigens, ribosomal RNP and Jo-1. The methods used for detection by the 28 European laboratories who participated included immunofluorescence, counter-immunoelectrophoresis, immunodiffusion, immunoblotting and ELISA. The results showed that only a combination of two or more techniques was able to detect all specificities with an adequate efficiency. Recommendations to improve the efficiency of autoantibody detection and to standardize laboratory protocols are given. PMID- 1906076 TI - Measurement of antigen specific lymphocyte proliferation using 5-bromo deoxyuridine incorporation. An easy and low cost alternative to radioactive thymidine incorporation. AB - The classical in vitro assay for the determination of cell mediated immune responses is the lymphocyte transformation test (LTT) in which cell proliferation is measured by incorporation of radioactive labeled thymidine (3H-TdR). The LTT assay using 3H-TdR is less suited for modestly equipped laboratories as it is costly, laborious and involves the need to handle radioactive isotopes and specialized equipment. Here we describe an improved alternative LTT method which is capable of detecting specific cellular immune reactions (CMI) against (mycobacterial) antigens in vitro. This assay, the bromodeoxyuridine-ELISA LTT test, is simple, less expensive, reproducible and is as sensitive as the 3H-TdR test. The specific advantages of the test are a simple denaturation step and the fact that no radioactive isotopes are needed. The test is specifically suited for research laboratories in tropical countries which study CMI in those human infectious diseases where this arm of the immune response plays a pivotal role in the generation of immunity, e.g., in tuberculosis, leprosy and leishmaniasis. PMID- 1906077 TI - Identification of unique murine tumor associated antigens by tumor infiltrating lymphocytes using tumor specific secretion of interferon-gamma and tumor necrosis factor. AB - Stimulation of multiple CD8+ murine tumor infiltrating lymphocyte (TIL) lines and one TIL clone with the tumor of origin of the TIL induced at least three-fold more secretion of TNF and/or INF-gamma than was elicited by other syngeneic, methylcholanthrene (MCA) induced sarcomas. TIL which specifically secreted lymphokines were generated from three different sarcomas. Specific lymphokine secretion was a stable characteristic of the lines over time. IL-2 was necessary for maximal lymphokine secretion by TIL. These investigations demonstrate that lymphokine secretion by CD8+ lymphocytes derived from tumor bearing mice can be used to define unique tumor associated antigens on at least three different sarcomas and may be valuable in studies of the biologic nature of these antigens and of the adoptive immunotherapy of cancer. PMID- 1906078 TI - [A study on the beta-lactamase production for Neisseria gonorrhoeae and the sensitivity to various antibacterial agents]. AB - During the 10-year period from 1980 through 1989 using gonococci isolated in Sapporo, we studied beta-lactamase production capacity and the sensitivity of various antibacterial agents and obtained the following results. 1. The frequency of isolating beta-lactamase producing gonococci (PPNG) displayed a gradual tendency to increase during the first half of the 80's and reached a peak in 1985 of 23.9% (61/255). However, thereafter it tended to decline and in 1989 it was 6.3% (2/32). 2. The sensitivity to penicillin-type antibacterial agents was higher against PPNG than non-PPNG against PCG, ABPC, and AMPC displaying about a 7 level MIC90 so that it was quite sensitive. Against CVA/AMPC, SBTPC it showed a relatively favorable MIC90. Also, the sensitivity of PPNG against AMPC with 1984 as the boundary, thereafter the MIC distribution was observed to decline somewhat. 3. Against the monobactam-type injectable drug, AZT, both non-PPNG and PPNG showed a low MIC distribution and against SPCM both showed a relatively high MIC distribution of 3.13-25 micrograms/ml. 4. In regard to the sensitivity to cephem-type antibacterial agents, against such 3rd generation injectables as CZX, CFTM-PI, etc. it displayed a particularly low MIC distribution. 5. Against tetracycline and macrolide antibacterial agents, it displayed a relatively high MIC distribution. 6. Against new quinolone type antibacterial agents, regardless of being non-PPNG or PPNG, it showed a low MIC. PMID- 1906079 TI - [Studies on tsutsugamushi disease in Gifu prefecture. 4. Survey results in Ena and Takayama City, and the summary of the studies in the prefecture]. AB - Investigations of trombiculid mites and Rickettsia tsutsugamushi in wild rodents were made in Ena (Nov. 1988) and Takayama (May 1989) City. In the former area where no patient has been reported so far, Leptotrombidium pallidum (63.9%) was most predominant and no L. scutellare was found. A Karp-related rickettsia (11.1%) was isolated from wild rodents and 30% of them had antibody to R. tsutsugamushi (anti-Karp was prominent). The latter area where patients were reported in spring as well as in autumn, L. pallidum (22.4%) was one of the dominant species in spring. Karp-related strains were isolated from 37.5% of wild rodents. And the antibody possession rate was 50.0%. These data reconfirmed our hypothesis that the majority of patients in autumn were infected by L. scutellare and a part by L. pallidum. In spring in Takayama area, the vector was L. pallidum which possessed Karp-related strain(s). PMID- 1906080 TI - [Pulsatile release of gonadotropins in athletic women]. AB - In athletic women menstrual disorders such as luteal insufficiency, oligomenorrhea and amenorrhea are often seen. It has been suggested that such disorders may be related to hypothalamic-pituitary axis insufficiency caused by physical activity. To investigate the mechanism by which the disorder is promoted, episodic gonadotropin secretion was studied in 10 athletic women (normal ovulatory, 5; short luteal, 5) and 6 non-athletic controls. In the early follicular phase of the menstrual cycle, blood samples were obtained through an indwelling venous catheter at 15-minute intervals for 4 hours. The concentrations of luteinizing hormone (LH) and follicle-stimulating hormones (FSH) were measured by radioimmunoassay. The mean LH and FSH concentrations in the athletic groups were lower than those in the control group. LH pulse frequencies in the short luteal group were 2.8 +/- 0.2 times/four hours (mean +/- standard error) and decreased compared with that of the control group (3.7 +/- 0.2 times/four hours; p less than 0.001). The LH pulse amplitudes of all three groups were similar. Pulsatile FSH secretion was also observed in all the women. Dynamism of FSH was the same as that of LH except for low pulse amplitude in the athletic groups. These data suggest that hypothalamic-pituitary axis insufficiency, especially of hypothalamic origin may be caused by athletic activity. PMID- 1906081 TI - [A study on GTP-binding protein in the activation of phospholipase C and phospholipase A2 in cultured rat luteal cells]. AB - We have studied the possible involvement of the GTP-binding protein (G-protein) in the activation of phospholipase C and A2 in cultured rat luteal cells as a transducer of cell information. 1. Inositol phosphate production and arachidonic acid release in rat luteal cells by the stimulation of PGF2 alpha and GnRH receptors are dependent on GTP and therefore suggest the involvement of GTP binding protein. 2. When the cells were not treated with IAP, a membrane protein of 41K molecular weight was apparently labeled. The protein, with a molecular weight of 41K, which was obtained from cultured rat luteal cells without prior treatment with IAP is considered to be the alpha-subunit of GTP binding protein as reported in other cells. While alpha-subunit of G-protein was ADP-ribosylated in luteal cells too, the 41K protein from the cells pretreated with IAP was not found to be ADP ribosylated. 3. When such IAP pretreated luteal cells were stimulated by PGF2 alpha or GnRHa, the production of inositol phosphate and the release of arachidonic acid were observed with no suppression. 4. The results suggest the existence of some G-protein other than Gi between the receptor and phospholipases C and A2. PMID- 1906082 TI - Classification of amyloidosis by the detection of clonal excess of plasma cells in the bone marrow. AB - In 28 cases of amyloidosis, bone marrow was examined to determine whether detection of clonal excess of plasma cells could be used to distinguish immunoglobulin-derived amyloidosis from other forms of amyloidosis. Patients were selected from a group of 315 cases of biopsy-proved amyloidosis in which bone marrow aspiration and biopsy had been done. There was no detectable monoclonal immunoglobulin in the serum or in the urine in 28 patients. Of 13 patients with immunoglobulin-derived amyloidosis, a clonal excess of plasma cells in the bone marrow could be detected in 11 (sensitivity, 85%), even though no immunoglobulin could be found circulating in the serum or urine after immunofixation with two light chain antisera of different sources. The 15 remaining patients had other forms of amyloidosis; 14 had polyclonal populations of plasma cells in the bone marrow (specificity, 93%). The positive predictive value of clonal excess was 92% and its negative predictive value was 88%. We conclude that, in the subset of patients with amyloidosis who do not have a circulating M component in the serum or urine detection of a clonal excess of plasma cells is useful in characterizing the type of amyloidosis. Correct classification is important for appropriate assessment of prognosis and therapy for the group of patients. PMID- 1906083 TI - Stereospecificity of the products of the fatty acid oxygenases derived from psoriatic scales. AB - The principal in vivo oxygenase products of arachidonic acid and linoleic acid in psoriatic skin scales are 12-hydroxyeicosatetraenoic acid (R/S ratio = 5.7), 13 hydroxyoctadecadienoic acid (S/R = 1.9), and 9-hydroxyoctadecadienoic acid (R/S = 2.4). Definition of the enzymatic origin of these fatty acid derivatives is an important step in assessing their possible role in the pathogenesis of psoriasis. Psoriatic skin scales were incubated with radiolabeled arachidonic acid and linoleic acid and the monohydroxylated derivatives produced in vitro were characterized. The products of incubation with [3H]arachidonic acid were an enantiopure 15(S)-[3H]hydroxyeicosatetraenoic acid and a nonracemic mixture of the 12-[3H]hydroxyeicosatetraenoic acid steroisomers (R/S ratio = 4.5). An enantiopure 13(S)-[14C]hydroxyoctadecadienoic acid was produced from [14C]linoleic acid. No radiolabeled products were derived from incubations with heat-denatured scales. These results provide evidence for two distinct oxygenase activities that are preserved in psoriatic skin scales. One is that of an omega-6 oxygenase with strict (S) stereospecificity, consistent with the activity of a lipoxygenase. This enzyme activity appears to be similar to that of the 15 lipoxygenase which has been described in cultured human keratinocytes. The second activity is that of an arachidonic acid 12(R)-oxygenase that has not been observed in normal human epidermis but which appears to be expressed in psoriatic epidermis. PMID- 1906084 TI - Altered particle size distribution of apolipoprotein A-I-containing lipoproteins in subjects with coronary artery disease. AB - Plasma high density lipoproteins (HDL) can be separated into two subpopulations of apolipoprotein A-I-containing particles: those that also contain apoA-II [Lp(AI w AII)] and those that do not [Lp(AI w/o AII)]. These particles were isolated by immunoaffinity chromatography from 17 men (9 normolipidemic (NL), 8 hyperlipidemic (HL) with symptomatic coronary artery disease (CAD), from 17 NL men without any symptoms of CAD (healthy controls), and from 10 NL men with entirely normal coronary arteriograms (CAD-free controls). The distributions of particle size in these two subpopulations were determined by gradient gel electrophoresis and densitometric scanning. Approximately half of the Lp(AI w AII) particles in all subjects were distributed in the 8.2-9.2 nm interval. For patients with CAD, a greater fraction of the particles were small, in the 7.0-8.2 nm interval [33% in CAD vs. 26% in CAD-free controls (P less than 0.01) and 19% in healthy controls (P less than 0.0001)], and a smaller fraction of the particles were in the 9.2-11.2 nm interval (14% in CAD vs. 24% in CAD-free control (P less than 0.002) and healthy control groups (P less than 0.001). The Lp(AI w/o AII) of both control groups were primarily composed of two discrete subpopulations in the 8.2-9.2 nm and the 9.2-11.2 nm intervals. In CAD patients there were fewer particles in the 9.2-11.2 nm size interval (23% in CAD vs. 33% in CAD-free controls (P less than 0.005) and 36% in healthy controls (P less than 0.0001), and more particles in the smallest 7.0-8.2 nm size interval (32% in CAD vs. 23% in CAD-free controls (P less than 0.01) and 18% in healthy controls (P less than 0.001]. Thus, the spectrum of HDL particle sizes in patients with CAD tends to be shifted toward the smaller particle when compared with the two control groups. This was observed in both NL and HL patients with HDL cholesterol (CH) values in the normal range. As a group, CAD patients had lower HDL (42 +/- 7 mg/dl) and HDL2 (6 +/- 4 mg/dl) CH than healthy (HDL: 49 +/- 7, HDL2: 12 +/- 6 mg/dl) and CAD-free (HDL: 51 +/- 9, HDL2: 12 +/- 6 mg/dl) controls. When controls and patients were compared for their frequencies of abnormal HDL CH levels and particle sizes, abnormalities in HDL and HDL2 CH levels were not significantly more frequent (twofold) among CAD patients than among controls.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1906085 TI - Effects of thyroid status and fasting on hepatic metabolism of apolipoprotein A I. AB - Metabolism of apolipoprotein (apo)A-I was studied in normal and chow-fed hyperthyroid rats, in 24-h fasted untreated male rats, and in rats after thyroparathyroidectomy (TXPTX). Rats were made hyperthyroid by administration of T3 (9.6 micrograms/day) or T4 (30 micrograms/day) with an Alzet osmotic minipump. Hyperthyroidism produced a similar two- to threefold elevation in plasma levels of apoA-I in male or female animals. During treatment with T3, plasma levels of T3 ranged from 200 to 400 ng/dl and did not correlate with plasma apoA-I levels. The net mass secretion and synthesis ([3H]leucine incorporation) of apoA-I by perfused livers from male hyperthyroid rats was elevated, while secretion of albumin was not different than that of euthyroid rats. Furthermore, the incorporation of [3H]leucine into total perfusate and hepatic protein was not altered by hyperthyroidism. The effect of thyroid hormone on apoA-I synthesis, therefore, does not appear to be a general effect on protein synthesis. After longer periods of treatment (28 days) with T3 (9.6 micrograms/day), hepatic apoA I production decreased from that observed after 7 or 14 days of treatment, yet plasma apoA-I concentrations remained elevated. Plasma T3 decreased from 100 ng/dl to 40 ng/dl, in the hypothyroid rat resulting from TXPTX, but the plasma concentration of apoA-I did not change during the 2-week experimental period. The net secretion of apoA-I by livers from hypothyroid animals was depressed and albumin was uneffected compared to the euthyroid. Overnight fasting of euthyroid rats did not alter hepatic apoA-I secretion or plasma apoA-I levels, although under fasting conditions we had reported that hepatic output of apoB and E of VLDL is depressed. The addition of oleic acid to the perfusion medium, sufficient to stimulate VLDL production, did not affect net hepatic secretion of apoA-I by livers from euthyroid, hyperthyroid, or hypothyroid rats. In summary, hepatic synthesis of apoA-I appears to be controlled independently of other apo lipoproteins and secretory proteins (albumin). Hepatic apoA-I synthesis is sensitive to thyroid status, increased in the hyperthyroid and decreased in the hypothyroid state. The specific stimulation of hepatic synthesis and secretion of apoA-I in the hyperthyroid state, however, tends to normalize over an extended period, perhaps from compensatory effects of a hormonal nature. PMID- 1906086 TI - Secretion of pre-beta-migrating apoA-I by cynomolgus monkey hepatocytes in culture. AB - Cynomolgus monkey hepatocytes that had been stored frozen were thawed, established in culture, and used to study apoA-I secretion. Protein synthetic activity was low at first, but increased with time, approaching what appeared to be the constitutive levels of the intact liver by day 7. During the first week, cellular RNA levels increased from 5.3 +/- 0.3 to 18.6 +/- 1.0 micrograms/10(6) cells; albumin secretion rates increased from undetectable to 55.4 micrograms/10(6) cells per day; apoA-I mRNA levels increased from 174 +/- 12 to 564 +/- 145 ng/10(6) cells; and apoA-I secretion rates increased from undetectable to 2.11 +/- 0.27 micrograms/10(6) cells per day. Analysis of day 7 conditioned media by agarose electrophoresis, gradient gel electrophoresis immunoblotting, and column chromatography, showed that the apoA-I produced by the cells was present in three distinct forms. One had an apparent molecular mass greater than 1 million Da, migrated pre-beta, and accounted for 11 +/- 3 (mean +/ SD)% of the total; one had an apparent molecular mass of 104 kDa, had alpha migration, and accounted for 27 +/- 2% of the total; and one had an apparent molecular mass of 50 kDa, migrated pre-beta, and accounted for 46 +/- 9% of the total. These data support the proposition that the pre-beta-migrating, 50 kDa, apoA-I-containing particles identified in the plasma of cynomolgus monkeys are nascent hepatic HDL. PMID- 1906087 TI - Evidence for a dominant role of lipoxygenase(s) in the oxidation of LDL by mouse peritoneal macrophages. AB - It has been suggested that the oxidative modification of low density lipoprotein (LDL) is a key event in atherogenesis. Several mechanisms have been proposed to explain how different types of cells modify LDL. In this study we examine the relative contributions of superoxide anions and cellular lipoxygenase (LO) in the modification of LDL by macrophages. Superoxide dismutase (SOD) inhibited LDL oxidation by macrophages but only by 25%. Under the same conditions, several LO inhibitors (eicosatetraynoic acid (ETYA), piriprost, and A-64077) almost completely inhibited the modification of LDL by macrophages. SOD had a greater inhibitory effect on the modification of LDL by U937 cells and fibroblasts (32% and 64%, respectively) but again LO inhibitors had a much greater effect (79 to 100% inhibition). Incubation of [1-14C]linoleic acid with mouse peritoneal macrophages resulted in its conversion to a single more polar product coeluting with 13- and 9-HODE by reverse phase HPLC. When the cells were preincubated with LO inhibitors, formation of this product was significantly inhibited. It is concluded that the modification of LDL by macrophages is mediated in large part by lipoxygenase-type activity. PMID- 1906088 TI - A disialoganglioside of the globo-series from chicken skeletal muscle. AB - We have isolated a disialoganglioside of the globo-series from chicken pectoral muscle. The compound was obtained by extraction followed by ion-exchange and silicic acid column chromatography and judged to be pure by thin-layer chromatography in three solvent systems. The structure of the ganglioside was determined by carbohydrate and ceramide composition analysis, sequential exoglycosidase digestion, methylation analysis, and 500-MHz 1H-NMR spectroscopy to be: (formula; see text) Analysis of the ceramide moiety indicated d18:1 sphingosine as the long-chain base, and C16:0, C18:0, C18:1, and C20:0 as the prevalent fatty acids. This glycolipid is only the second ganglioside of the globo-series, and the first disialo member of the series, found in chicken muscle. PMID- 1906089 TI - Effect of administration of testosterone and gonadotrophin-releasing hormone (GnRH) antagonist on basal and GnRH-stimulated gonadotrophin secretion in orchidectomized monkeys. AB - The aim of the present investigation was to investigate the effects of testosterone on basal and gonadotrophin-releasing hormone (GnRH)-stimulated gonadotrophin secretion in the presence and absence of a GnRH antagonist in a non human primate model (Macaca fascicularis). Orchidectomized animals were used in order to avoid interference by testicular products other than testosterone involved in gonadotrophin feedback. Concomitant and delayed administration of testosterone at doses that provided serum levels either within the intact range (study 1) or markedly above that range (study 2) did not influence the suppression of basal gonadotrophin release induced by the GnRH antagonist during a 15-day period. To assess the possible effects of testosterone treatment at the pituitary level (study 3) GnRH stimulation tests (500 micrograms) were performed before and on days 8 and 15 of treatment with high-dose testosterone and GnRH antagonist alone or in combination. Testosterone alone abolished the gonadotrophin responses to exogenous GnRH observed under pretreatment conditions. With GnRH antagonist alone, an increased responsiveness (P less than 0.05) to GnRH was seen on day 8 and a similar response compared with pretreatment on day 15. Following combined treatment with GnRH antagonist and testosterone, GnRH induced gonadotrophin secretion was consistently lower compared with that after GnRH antagonist alone (P less than 0.05), but was increased compared with that after testosterone alone (P less than 0.05). Thus, in the presence of a GnRH antagonist the feedback action of testosterone on LH and FSH was diminished.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1906090 TI - Early postoperative basal serum GH level and the GH response to TRH in relation to the long-term outcome of surgical treatment for acromegaly: a report on 39 patients. AB - During a 10-year period 39 patients with acromegaly, aged 23-73 years, underwent selective adenomectomy via a trans-sphenoidal or transfrontal (one case) approach. Six to 12 months after the operation, the serum level of growth hormone (GH) was reduced to less than 5 micrograms l-1 in 28 patients (74%) in at least two of three random samples and/or suppressed to less than 3 micrograms l-1 during an oral glucose load, thus fulfilling the commonly used criteria for a successful operation. In 10 patients these criteria for adequate GH reduction were not fulfilled, but their median S-GH level was reduced from 38 to 11 micrograms l-1 (P less than 0.01) after the operation. Surgery was successful in 11 of 13 (85%) patients with a microadenoma (less than 10 mm in diameter), in 10 of 14 (71%) patients with an adenoma of diameter greater than 10 mm but still enclosed in the sella, and in seven of 11 (64%) patients with locally invasive tumours. Impaired pituitary function was observed in 23% of the patients after surgery, independent of tumour size. In one patient the postoperative period was complicated by a lethal intracranial infection. During follow-up for 1-10 years, four patients relapsed, after 1, 1.5, 6 and 9 years, respectively. Patients for whom surgery appeared to have been ineffective at the evaluation 6-12 months postoperatively, or who later relapsed were identified by early (within 7 d) postoperative serum GH with a sensitivity of 90%. The accuracy for identification of a satisfactory outcome of surgery was 85%, and the predictive value was 90%. The corresponding values for the GH response to TRH measured 6-12 months postoperatively were 47, 40 and 54%, respectively. It is concluded that the basal level of serum GH measured 1-7 d postoperatively has higher sensitivity and specificity than the GH response to TRH 6-12 months postoperatively for evaluation of the effect of surgery on GH overproduction, and that it has a higher predictive power with regard to the long-term outcome of surgery for acromegaly. PMID- 1906091 TI - Spreading depression increases immunohistochemical staining of glial fibrillary acidic protein. AB - Reactive astrocytosis is a process by which astrocytes respond to brain injury by showing an increase in glial fibrillary acidic protein (GFAP) staining that is associated with hypertrophy and/or hyperplasia of these cells. Because spreading depression (SD) is a perturbation uncomplicated by neuronal necrosis and is seen in both in vivo and in vitro neural structures, we sought to determine whether SD was a sufficient stimulus to induce enhanced GFAP staining. SD was elicited in anesthetized rats by application of KCI to parietal cortex for 3 hr; equimolar NaCI was applied to contralateral cortex. SD was confirmed by monitoring DC potentials in frontal neocortices. Animals were allowed to recover for 48 hr, and their brains were processed for semiquantitative and computer-based analyses of GFAP staining intensity. Experimental GFAP staining was referenced to contralateral control levels. Neocortical SD (13-37 SDs) was associated with a significant (p less than 10(-4)), 43% increase in GFAP staining intensity, which remained statistically greater than normal for more than 2 weeks. If SD was inhibited by combined hyperoxia and hypercarbia, only a nonsignificant (p greater than 0.20), 7% increase in GFAP staining was seen. Thus, SD may be a useful physiologic process with which to begin to explore the cellular mechanisms that induce the transformation of normal astrocytes into reactive species. PMID- 1906092 TI - The action of halothane on stimulus-secretion coupling in clonal (GH3) pituitary cells. AB - The effect of halothane on the physiological response to excitatory stimuli was assessed in clonal (GH3) pituitary cells. Halothane, at concentrations used to produce general anesthesia in animals (0.25-0.76 mM), inhibited thyrotropin releasing hormone (TRH)-induced prolactin (PRL) secretion. The sustained (extracellular calcium-dependent) phase of PRL secretion was 70 +/- 7% inhibited by the highest concentration of halothane tested (0.76 mM); 50% inhibition was produced by approximately 0.4 mM halothane. The early (largely inositol trisphosphate-mediated) phase of secretion was less sensitive to halothane; 0.76 mM halothane produced 18 +/- 2% inhibition of the early phase of secretion. Consistent with these observations, halothane inhibited (IC50 approximately 0.45 mM) the sustained phase of the TRH-induced rise in intracellular calcium ([Ca2+]i) to a greater extent than the initial [Ca2+]i peak. The sustained phase of the [Ca2+]i elevation was inhibited by 75 +/- 7% at the highest concentration of halothane tested (0.76 mM), whereas the peak [Ca2+]i was only inhibited by 14 +/- 5%, consistent with the observation that halothane did not inhibit TRH stimulated inositide hydrolysis in these cells. Halothane (0.5 mM) did not inhibit phorbol ester- or ionomycin-induced PRL secretion, indicating that halothane has inconsequential effects on the secretory apparatus. Halothane (0.5 mM) also inhibited KCl-induced PRL secretion by 50-80% and the corresponding KCl induced rise in [Ca2+]i by 68 +/- 6%. These data indicate that halothane inhibits secretagogue-stimulated PRL secretion by reducing the elevation of [Ca2+]i produced by calcium (Ca2+) influx.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1906093 TI - Increased amino acid transport into brain tumors measured by PET of L-(2 18F)fluorotyrosine. AB - The uptake of L-(2-18F)fluorotyrosine (F-Tyr), a newly synthetized amino acid tracer, was studied in 15 patients with various brain tumors by dynamic PET. The higher F-Tyr accumulation in tumors (mean 27% above contralateral tissue) was associated with two-fold transport rates into tumors, while the rate constants describing irreversible incorporation were decreased. The increased F-Tyr transport was not correlated to 68Ga-EDTA accumulation and cannot be explained by disruption of the blood-brain barrier. Kinetic analysis of 2-(18F)-fluoro-deoxy glucose accumulation in the same patients demonstrated that increased metabolic rates in tumors are mainly caused by altered phosphorylation rates while transport of glucose is less affected. Since F-Tyr transport rates clearly separated tumors from normal tissue and since F-Tyr accumulation was related to tumor grade, PET studies of F-Tyr uptake are of clinical value for diagnosis and classification of brain tumors. PMID- 1906094 TI - Postinjection L-phenylalanine increases basal ganglia contrast in PET scans of 6 18F-DOPA. AB - The sensitivity of 18F-DOPA positron emission tomography for imaging presynaptic dopamine systems is limited by the amount of specific-to-nonspecific accumulation of radioactivity in brain. In rhesus monkeys, we have been able to increase this ratio by taking advantage of the lag time between 18F-DOPA injection and the formation of its main metabolite, the amino acid 18F-fluoromethoxydopa, the entrance of which into brain is responsible for most of the brain's nonspecific radioactivity. By infusing an unlabeled amino acid, L-phenylalanine, starting 15 min after 18F-DOPA administration, we preferentially blocked the accumulation of 18F-fluoromethoxydopa by preventing its entrance into brain through competition at the large neutral amino acid transport system of the blood-brain barrier. This method appears as reliable as the original and more sensitive, as demonstrated by the comparison of normal and MPTP-treated animals under both conditions. PMID- 1906095 TI - Deficit reduction and healthcare expenditures. A macroeconomic perspective. AB - The federal budget deficit is one of the more serious problems facing the U.S. economy, and reductions in the deficit have been mandated by Congress. Using a macroeconomic perspective, the authors discuss the potential direct and indirect effects of deficit reduction on the healthcare industry. Strategies for nurse executives to deal with pressures resulting from a changing macroeconomy are addressed. PMID- 1906096 TI - Formulary policy for cholesterol reduction. PMID- 1906097 TI - Cefixime compared with amoxicillin for treatment of acute otitis media. AB - Cefixime was compared with amoxicillin for treatment of acute otitis media in a randomized trial. Results of tympanocentesis on day 3 to 5 of therapy were used as the major outcome. Total daily doses were 8 mg/kg of cefixime and 40 mg/kg of amoxicillin. One hundred twenty-six patients were randomly assigned to receive treatment; 64 cultures grew pathogens. Pathogens were eradicated from the middle ear after 3 to 5 days of therapy in 27 (79.4%) of 34 children given amoxicillin and 26 (86.7%) of 30 children given cefixime (p = 0.47). When Streptococcus pneumoniae cases were analyzed, bacteriologic cure occurred in 14 (93.3%) of 15 children given amoxicillin and 12 (75%) of 16 given cefixime (p = 0.333). When cases of Haemophilus influenzae infection were analyzed, significantly more cures occurred with cefixime (10/10, 100%) than amoxicillin (8/13, 62%) (p = 0.046). Pathogens associated with failure of amoxicillin therapy were H. influenzae (five cases, two beta-lactamase-positive), S. pneumoniae (one case), and Moraxella catarrhalis (one case, beta-lactamase-positive). The four failures with cefixime therapy were all in patients infected with S. pneumoniae. Rates of rash, diarrhea, and vomiting were the same in both groups and did not necessitate stopping therapy. We conclude the following: (1) Cefixime and amoxicillin were equivalent in overall clinical and bacteriologic efficacy for otitis media. (2) Cefixime was more efficacious than amoxicillin in treating H. influenzae otitis media and should be preferred when H. influenzae is the suspected etiologic agent. (3) Side effects of both drugs were mild and equivalent. PMID- 1906098 TI - Myopathy in human immunodeficiency virus-infected children receiving long-term zidovudine therapy. PMID- 1906099 TI - Neonatal short bowel syndrome. AB - In this retrospective study the management of infants who had undergone resection of more than 50% of the small bowel as newborn infants between 1970 and 1988 was analyzed to define prognostic factors. Small bowel resections were performed for atresia (36 cases), volvulus (22 cases), gastroschisis (10 cases), necrotizing enterocolitis (11 cases), and other disorders (8 cases). Patients were classified into two groups depending on the length of residual small bowel: group 1 (n = 35) had less than 40 cm of small bowel and group 2 (n = 51) had 40 to 80 cm of residual small bowel. Patients in group 2 had significantly better survival rates than those in group 1 (92.0% vs 66.6%; p less than 0.001). The patients in group 1 who were born after 1980, when home parenteral nutrition was introduced, had better survival rates than those who were treated before 1980 (95.0% vs 65.0%; p less than 0.01). The time required for acquisition of intestinal adaptation depended on the intestinal length (average, 27.3 months for group 1 and 14 months for group 2; p less than 0.01) and on the presence or absence of the ileocecal valve. Parenteral or supportive enteral nutrition, or both, ensured normal growth in both groups. We conclude that more than 90% of infants now survive after extensive small bowel resection with parenteral nutrition and that the remaining small intestine will adapt with time. Home-based parenteral nutrition allowed children to be treated in the best psychosocial environment. PMID- 1906100 TI - Effects of perinatal polychlorinated biphenyls and dichlorodiphenyl dichloroethene on later development. AB - OBJECTIVE: Determining whether early developmental effects of perinatal exposure to polychlorinated biphenyls (PCBs) or dichlorodiphenyl dichloroethene (DDE) persist. DESIGN: Cohort followed from birth; ages now 5 1/2 to 10 1/2 years. SETTING: General community. PARTICIPANTS: Volunteer sample of 859 children, of whom 712 had been examined with the McCarthy Scales of Children's Abilities at 3, 4, or 5 years; 506 sent report cards. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Neither transplacental nor breast-feeding exposure to PCBs or DDE affected McCarthy scores at 3, 4, or 5 years. There was no statistically significant relationship between poorer grades and PCB or DDE exposure by either route. CONCLUSIONS: The deficits seen in these children on the Bayley Scales of Infant Development through 2 years of age are no longer apparent. PMID- 1906101 TI - False-positive result of hepatitis C enzyme-linked immunosorbent assay in children with autoimmune hepatitis. PMID- 1906102 TI - Multicenter controlled trial comparing high-frequency jet ventilation and conventional mechanical ventilation in newborn infants with pulmonary interstitial emphysema. AB - One hundred forty-four newborn infants with pulmonary interstitial emphysema were stratified by weight and severity of illness, and randomly assigned to receive treatment with high-frequency jet ventilation (HFJV) or rapid-rate conventional mechanical ventilation (CV) with short inspiratory time. If criteria for treatment failure were met, crossover to the alternate ventilatory mode was permitted. Overall, 45 (61%) of 74 infants met treatment success criteria with HFJV compared with 26 (37%) of 70 treated with CV (p less than 0.01). Eighty-four percent of patients who crossed over from CV to HFJV initially responded to the new treatment, and 45% ultimately met success criteria on HFJV. In contrast, only 9% of those who crossed over from HFJV to CV responded well to CV (p less than 0.01), and the same 9% ultimately met success criteria (p less than 0.05). Therapy with HFJV resulted in improved ventilation at lower peak and mean airway pressures, as well as more rapid radiographic improvement of pulmonary interstitial emphysema, in comparison with rapid-rate CV. Survival by original assignment was identical. When survival resulting from rescue by the alternate therapy in crossover patients was excluded, the survival rate was 64.9% for HFJV, compared with 47.1% for CV (p less than 0.05). The incidence of chronic lung disease, intraventricular hemorrhage, patent ductus arteriosus, airway obstruction, and new air leak was similar in both groups. We conclude that HFJV, as used in this study, is safe and is more effective than rapid-rate CV in the treatment of newborn infants with pulmonary interstitial emphysema. PMID- 1906103 TI - Selective pulmonary vasodilation by low-dose infusion of adenosine triphosphate in newborn lambs. AB - The systemic and pulmonary vascular effects of adenosine 5'-triphosphate (ATP) were investigated in 12 newborn lambs during normoxia and during alveolar hypoxia (10% oxygen, 5% carbon dioxide, and 85% nitrogen). Lambs had catheters in the descending aorta, main pulmonary artery, and were studied after a 3-day recovery. We infused ATP or an equal volume of saline solution (control) into the right atrial line in doses ranging from 0.01 to 2.5 mumol/kg per minute. In normoxic lambs, ATP caused a significant decrease in pulmonary vascular resistance in doses of 0.08 to 2.5 mumol/kg per minute, and in systemic vascular resistance in doses of 0.3 to 2.5 mumol/kg per minute. Infusion of ATP in hypoxic lambs caused decreases in pulmonary artery pressure and pulmonary vascular resistance in all the doses tested. Systemic vascular resistance decreased, and cardiac output and heart rate increased in doses greater than 0.3 mumol/kg per minute in hypoxic lambs during ATP infusion. The effects of ATP in hypoxic lambs were not blocked by propranolol, indomethacin, or theophylline. Plasma ATP levels in left atrial blood samples did not change significantly during the infusion of ATP. We conclude that ATP is a vasodilator in lambs, and its effects are specific for pulmonary circulation at doses of less than or equal to 0.15 mumol/kg per minute. The vasodilator effects of ATP appear to be independent of P1 purinergic and beta adrenergic mechanisms, and of prostacyclin synthesis. PMID- 1906104 TI - [From nucleic acids to proteins]. AB - Since elucidation of structure of deoxyribonucleic acid (DNA) as genetic material, it was established that DNA makes ribonucleic acid, which makes protein according to the original information given in DNA base as base sequences. From these basic idea of genetic flow system there was emerged the word "protein engineering". According to this principle, engineering of h-lysozyme, RNase H and their relevant proteins was described. A triosephosphate isomerase barrel type protein was designed and expressed. PMID- 1906105 TI - Effect of IFN-gamma on the expression of MHC class I and class II antigens in a human malignant oral epithelial cell line. AB - This study examined the expression of major histocompatibility complex (MHC) antigens in the KB human carcinoma cell line. MHC class I antigens (HLA-ABC and beta 2microglobulin) were constitutively expressed but not significantly enhanced by interferon-gamma (IFN-gamma). By contrast, MHC class II antigens were absent or expressed minimally on unstimulated KB cells, but DR and DP were significantly stimulated in a non-coordinated pattern (HLA-DR greater than -DP greater than DQ) by IFN-gamma. PMID- 1906106 TI - Low incidence of toxicity from gold thiomalate in Hong Kong Chinese patients with rheumatoid arthritis. PMID- 1906107 TI - Additional nucleotide derivatives of mitosenes. Synthesis and activity against parental and multidrug resistant L1210 leukemia. AB - Cytidine 5'-monophosphate and 5'-ara-CMP conjugates of 2,7-diaminomitosene, with the phosphate groups linked to C-1, were prepared by treating mitomycin C with the appropriate nucleotides. 5'-UMP conjugates were prepared from mitomycin A, 7 (M-83), and 8 (BMY-25282) by similar procedures. A conjugate could not be prepared from mitomycin C and 6-MPRP, but a sulfur-linked derivative was made with 6-MP ribonucleoside. The corresponding 1-hydroxy-2-aminomitosenes were prepared from the parent mitomycin analogues for structure-activity comparisons. All compounds were tested against L1210 murine leukemia in the MTT tetrazolium dye assay. In general, the conjugates were less potent than the parent mitomycins; however 5'-ara-CMP conjugate 14 derived from mitomycin C was more potent than the parent compound or any mitomycin tested except mitomycin A. It also was more potent than ara-C. This result establishes the value of this approach to prodrugs, at least in cell culture. Against a multi-drug-resistant L1210 cell line, all of the conjugates derived from mitomycin C were more potent than the parent compound. 6-Mercaptopurine ribonucleoside conjugate 15 was more active against the resistant cells than it was against the parental cell line. PMID- 1906108 TI - Relative structure-inhibition analyses of the N-benzoyl and N-(phenylsulfonyl) amino acid aldose reductase inhibitors. AB - A number of N-benzoyl amino acids were synthesized and tested to compare structure-inhibition relationships with the isosteric N-(phenylsulfonyl) amino acid (PS-amino acid) aldose reductase inhibitors. Inhibition analyses with these series reveals that their kinetic mechanisms of inhibition are similar, but that significant differences in structure-inhibition relationships exist. For example, while the PS-alanines and PS-2-phenylglycines produce enantioselective inhibition (S greater than R), no consistent pattern of enantioselectivity is observed with the isosteric N-benzoylalanines and 2-phenylglycines. Also, N-methyl and N-phenyl substitution in the PS-amino acid series does not substantially alter inhibitory activity, while similar substitutions in the N-benzoyl series (particularly N phenyl) results in a significant increase in inhibitory activity. Proton NMR analysis of the N-benzoylsarcosines reveals that these compounds exist as a mixture of rotamers in solutions including the enzyme assay buffer and that the preferred conformer is one in which the carboxymethyl moiety is trans to the aromatic ring. Similar analyses with the N-benzoyl-N-phenylglycines demonstrate that these derivatives exist exclusively in the trans rotameric conformation in solution. No such N-substituent effects on conformation were observed in the PS amino acid series. These results suggest that the differences in structure inhibition trends between these structurally related series may result from the effect of substituents on preferred conformation. PMID- 1906109 TI - Structure-activity relationships for mitomycin C and mitomycin A analogues. AB - A set of 30 mitomycin C and mitomycin A analogues, including five new compounds, was screened against three different solid human tumor cell lines using the MTT tetrazolium dye assay. A statistically significant correlation among antitumor activity, quinone reduction potential (E1/2), and the logarithm of the partition coefficient (log P) was obtained, with the most easily reduced and the most lipophilic compounds being the most potent. When these analogues were separated into mitomycin C and mitomycin A subsets, the former gave a correlation only with E1/2, whereas the latter (which differ little in their E1/2 values) gave a correlation only with log P. These correlations are in contrast to those made in the P388 leukemia assay in mice wherein the most active mitomycin C and mitomycin A analogues were the most hydrophilic ones. When the same compounds were tested against P388 leukemia cells in the MTT assay, the results were the same as those of the solid tumor assays. Thus, the substantial differences in relative potencies of mitomycins are related not to the kind of tumor cell, but to the type of assay performed, cell culture versus whole animal. No correlation was found between antitumor potency in the cell culture systems and calculated relative DNA binding strengths, probably because the limiting factors in antitumor potency of mitomycins appear to be tumor cell uptake (log P) and/or bioreductive activation (E1/2). PMID- 1906110 TI - Molecular size and symmetry of Pseudomonas aeruginosa catabolic ornithine carbamoyltransferase. An X-ray crystallography analysis. AB - The catabolic ornithine carbamoyltransferase (EC 2.1.3.3) from Pseudomonas aeruginosa, that shows allosteric behaviour, and a mutant version of this enzyme has been crystallized in several different crystal forms. All of these have been characterized by X-ray diffraction methods. A 4.5 A resolution data set has been collected on a triclinic crystal. Analysis of the data using the self-rotation function shows that 12 monomers associate to form a particle with cubic 23 point group symmetry. PMID- 1906111 TI - High-dose chemotherapy with reinfusion of purged autologous bone marrow following dose-intense induction as initial therapy for metastatic breast cancer. AB - We assessed the toxicity and efficacy of high-dose chemotherapy consolidation with reinfusion of purged autologous bone marrow in women with metastatic breast cancer responding to a dose-intense outpatient regimen. Thirty women with hormone unresponsive metastatic breast cancer, previously untreated with adjuvant doxorubicin or with any chemotherapy for metastatic disease, were treated with cyclophosphamide, methotrexate, doxorubicin, fluorouracil, vincristine, and leucovorin for 16 weeks. Twenty-four patients responded to therapy; 8 showed a complete response, and 16 showed a partial response. These patients proceeded to the next phase of the protocol, ie, marrow harvest and treatment with 6000 mg/m2 cyclophosphamide and 800 mg/m2 thiotepa given over 4 days. Harvested marrow was purged with 100 micrograms/mL 4-hydroperoxycyclophosphamide, and all patients engrafted satisfactorily. The predominant side effects were myelosuppressive and gastrointestinal, and there were no deaths from toxic effects. Three of the 16 patients who showed a partial response after the outpatient phase of treatment achieved a complete response after high-dose therapy. The partial response seen in two more patients converted to a complete response at all sites except bone. The median time to disease progression for all patients in this study was 13 months, and the median survival was 22 months. Four of the original 30 patients remained without disease progression a median of 27 months from entry into the study. This study indicates that this dose-intense regimen can be safely administered, even with the use of purged marrow, with an acceptable toxicity profile. This approach results in a high response rate in women with metastatic breast cancer and could form the basis for a regimen to be tested in the high risk adjuvant setting. PMID- 1906112 TI - Ultrastructure of the cyst and life cycle of Sarcocystis sp. from wild sheep (Ovis musimon). AB - Sarcocystis sp. (Eimeriina: Sarcocystidae) is described as a heteroxenous coccidian with domestic dogs as an experimental definitive host and wild sheep (Ovis musimon) as natural intermediate hosts. Mature sarcocysts of this Sarcocystis sp. were examined by transmission electron microscopy. Sarcocysts in various muscle tissues were microscopic, had a thin primary cyst wall and septa and measured 81.0 x 30.5 microns. The cysts were located within muscle cells and were limited by a primary cyst wall (PCW). The cyst surface was highly folded forming densely packed projections. Between the PCW projections the surface of the cyst was marked with pit-like invaginations. The ground substance of the cyst formed a layer at the periphery of the cyst, filled the projections and formed septa which divided the cyst into compartments. Sarcocysts contained numerous bradyzoites that were 15.2 x 3 microns and few metrocytes 11.5 x 3.5 microns. Twelve days after ingesting Sarcocystis sp.-infected wild sheep meat, four dogs began passing sporocysts in their feces: two domestic cats did not pass oocysts or sporocysts after ingesting meat from the same animals. Sporocysts measured 14.8 x 9.9 microns. PMID- 1906113 TI - Serological evidence of California group and Cache Valley virus infection in Minnesota white-tailed deer. AB - Blood samples were obtained from 138 white-tailed deer (Odocoileus virginianus) harvested at three sites surrounding the greater Minneapolis-St. Paul, Minnesota, metropolitan area (USA) and tested for neutralizing antibody to Cache Valley virus and three California serogroup (Jamestown Canyon, La Crosse, trivittatus) viruses (Bunyaviridae). Deer at each site had neutralizing antibody to one or more California serogroup viruses and/or Cache Valley virus. The majority of adult deer (85%) had antibody to both a California serogroup virus and Cache Valley virus. Antibody prevalence varied significantly with age of the deer. Fawns had a significantly lower prevalence of antibody to either a California serogroup (17%) or Cache Valley virus (39%) than did older (greater than 1-yr old) deer (89% for a California serogroup virus and 91% for Cache Valley virus). The geometric mean titers of antibody in fawns to California serogroup (1:6) and Cache Valley viruses (1:17) were also less than that seen in older animals (1:11 and 1:28 for California serogroup and Cache Valley viruses, respectively). Of 76 older deer with antibody to the California serogroup, 91% had antibody specific for Jamestown Canyon virus. Jamestown Canyon is the primary California serogroup virus circulating in the suburban/rural Minneapolis-St. Paul area. Transmission occurs in an enzootic pattern similar to that documented in Indiana and Michigan. Cache Valley virus also appears to be enzootically transmitted in this area. However, the impact on domestic or wild animal populations is unknown. PMID- 1906114 TI - Brucella abortus in Bison. II. Evaluation of strain 19 vaccination of pregnant cows. AB - Protection against Brucella abortus induced abortion and infection provided by strain 19 (S19) vaccination was evaluated in American bison (Bison bison). Forty eight pregnant bison were manually inoculated (MI) with S19 vaccine, 44 were ballistically inoculated (BI) with an absorbable hollow pellet containing lyophilized S19, and 46 were manually injected with buffered saline as non vaccinated controls (NVC). All bison were Brucella spp. seronegative prior to the experiment, in the second trimester of pregnancy, and were randomly assigned to experimental groups. Approximately 60 days post-vaccination, abortions were observed in the vaccinated bison. Brucella abortus strain 19 was recovered from a bison that had recently aborted, her fetus, and from 11 of 12 other aborted fetuses. Fifty-eight percent (53 of 92) of vaccinated bison aborted, and no abortions were observed in the NVC bison. One cow aborted during her second post vaccinal pregnancy and S19 was identified from the dam and fetus indicating that chronic S19 infections can occur in bison. Positive antibody titers were present 10 mo post-vaccination in 73% (66 of 91) of the bison. Thirteen mo post vaccination, 30 MI vaccinates, 27 BI vaccinates, and 30 NVC bison were challenged during the second trimester of pregnancy with 1 x 10(7) CFU of B. abortus strain 2308 via bilateral conjunctival inoculation. Protection against abortion was 67% (P less than or equal to 0.0001) for vaccinated bison compared to 4% in NVC. Protection against B. abortus infection was determined to be 39% (P greater than or equal to 0.001) for vaccinates and 0% (zero of 30) for NCV. Persistent antibody titers, vaccine induced abortions, and chronic S19 infections indicate that the S19 vaccine doses used in this study are not suitable for pregnant bison. PMID- 1906115 TI - [Control of graft-versus-host disease and infection associated with immunosuppression]. AB - Graft-versus-host disease (GVHD) in leukemia patients following allogeneic bone marrow transplantation (BMT) has a lot of demerits but it also has a merit, namely graft-versus-leukemia effect. We reported the results of our recent trials on prevention, treatment and induction of GVHD, and prevention of viral infection after BMT. The results were as follows: 1) Twenty-four percent of patients who received prophylactic administration of cyclosporine and short term methotrexate still developed II degree-IV degree acute GVHD. 2) Patients with I degree or II degree acute GVHD showed good clinical courses. But, most patients with III degree GVHD gradually developed chronic GVHD. All patients with IV degree GVHD died of GVHD or infection. 3) Mizoribine and deoxyspergualin were effective for steroid-resistant GVHD. 4) Bestatin was administered to recipients who did not develop GVHD until day 30 after BMT. An interim report suggests that bestatin may induce chronic GVHD and suppress the relapse of leukemia. 5) Oral administration of gamma-globulin may prevent viral enteritis. Intravenous administration of anti cytomegalovirus monoclonal antibody may prevent cytomegalovirus pneumonia. PMID- 1906116 TI - [IgD-lambda multiple myeloma associated with bone marrow fibrosis]. AB - A few cases of multiple myeloma associated with myelofibrosis has been reported. In Japan, such cases have been less reported. We report a case of IgD-myeloma with remarkable marrow fibrosis. A 44-year-old female was admitted to our hospital because of back pain. On admission her peripheral blood revealed anemia and leukopenia. Serum immunoelectrophoresis revealed M-protein of IgD and serum IgD level remarkably increased to 5420 mg/dl. Bone marrow aspiration resulted in dry tap every three times and its biopsy at iliac bone showed remarkable infiltration of myeloma cell and remarkable increase of reticulin fiber with marked decrease of normal hematopoietic cells. Her liver and spleen were not palpable and tear drop cells of erythrocytes were not shown in peripheral blood. We could not find view of myelofibrosis with chronic myeloproliferative disorders. Multiple myeloma associated with myelofibrosis is a interesting syndrome as clinical signs and course. So further investigation must be needed. PMID- 1906117 TI - [Richter's syndrome with identical immunoglobulin gene rearrangements]. AB - A 75-year-old man was admitted to our hospital because of hepatosplenomegaly, generalized lymphadenopathy and lymphocytosis in February, 1989. The leukocyte counts were 93,200/microliters with 95% small lymphocytes which expressed surface membrane immunoglobulin (SmIg) M, D and kappa. Histological finding of the cervical lymph node was diffuse small cell lymphoma. A diagnosis of chronic lymphocytic leukemia (CLL) was made. He was followed up without chemotherapy. In January, 1990, he was re-admitted because of progressively enlarged lymph nodes and increased white blood cell counts, up to 183,200/microliters with 98% lymphocytes. He was treated with vincristine, cyclophosphamide, prednisolone. The leukocyte counts decreased to 5,000/microliters and lymph node swelling decreased in size. In April, 1990, generalized lymphadenopathy re-appeared. The biopsied lymph node specimen showed diffuse large cell non-Hodgkin lymphoma (NHL-DL). The lymph node cells were found to express SmIgM and kappa. The diagnosis of Richter's syndrome was made. DNA analysis using Southern blot method revealed identical immunoglobulin heavy and kappa chain gene rearrangements in the two neoplasms. These findings suggest that the CLL cells and the NHL-DL cells originate from the same clone in this case. PMID- 1906118 TI - Effects of sequential and combined immuno-endocrine therapies using OK-432 (Picibanil) and tamoxifen on the growth of 7,12-dimethylbenz [alpha] anthracene induced rat mammary carcinoma. AB - Effects of sequential and combined immuno-endocrine therapies using OK-432 (Picibanil) and tamoxifen (TAM) on the growth of 7,12-dimethylbenz [alpha] anthracene (DMBA)-induced carcinoma were examined in 128 female Sprague-Dawley (SD) rats. The rats were divided into six groups: control (no treatment), tamoxifen, OK-432, simultaneous immuno-endocrine OK-432 and TAM (OK-432 + TAM) therapy, two types of sequential immuno-endocrine therapy of the OK-432 and TAM groups [OK-432 (1 wk)----TAM (4 wk) and OK-432 (2 wk)----TAM (3 wk)]. Each group was treated consecutively for five weeks. The response rates in the TAM alone group, the [OK-432 (1 wk)----TAM (4 wk)] group and the [OK-432 + TAM (5 wk)] group were significantly higher than in the control group. When the results among the treated groups were compared, the response rate in the [OK-432 (1 wk)----TAM (4 wk)] group was significantly higher than in the OK-432 alone or TAM alone groups. The response rate in the [OK-432 (2 wk)----TAM (3 wk)] group, however, was lower than in the TAM alone group. The response rate in the OK-432 + TAM group was, moreover, not significantly superior to that in the TAM alone group. These results suggest OK-432 not to potentiate the antitumor effect of TAM since the response rate of the combined OK-432/TAM therapy was not always significantly superior to that of the TAM treatment. PMID- 1906119 TI - Pharmacological study of TA-0910, a new thyrotropin-releasing hormone (TRH) analog (IV): Effects on experimental memory impairment in mice and rats. AB - The effects of a new TRH analog, TA-0910, orally administered, on experimental memory impairments for the one-trial passive avoidance response in anoxic mice (light-dark box), active avoidance response in basal forebrain (BF)-lesioned rats (shuttle box), and delayed alternation task in scopolamine-treated rats (T-maze) were studied. In mice, TA-0910 (3-30 mg) administered 60 min before the retention trial dose-dependently prolonged the passive avoidance response latency reduced by CO2-exposure that was given immediately after the acquisition trial, but not when it was given 60 min before the acquisition or just after the anoxic treatment. In rats, TA-0910 (0.3-3 mg/kg) administered 40-60 min before the test trial, dose-dependently prevented the reduction in mean avoidance rate caused by BF-lesioning and elevated the scopolamine (0.1 mg/kg, i.p.)-induced reduction in percent correct choice level in the alternation task. TRH (30-300 mg/kg), on the other hand, produced no improvements in any of the above tests. These results suggest that TA-0910 improves impaired memory by correcting the retrieval process of memory. PMID- 1906120 TI - [State of the hypophyseal-gonadal system in patients with hypertension during long-term treatment with nadolol and anaprilin]. AB - The changes in hormone levels of the hypophyseal-gonadal system were studied during 6-month monotherapy with nadolol, 40-160 mg/day, or anaprilin, 80-240 mg/day, in 40 males with Stage II hypertensive disease. Serum levels of prolactin, luteinizing, follicle-stimulating, and testicular hormones, and estradiol were measured by radioimmunoassay at the end of control placebo, 2 week, 2- and 6-month therapy. The negative changes revealed in the hypophyseal gonadal system, as manifested by elevated prolactin and estradiol levels, diminished testicular hormone concentration, indicate that the levels of these hormones should be monitored in a long-term antihypertensive therapy with beta adrenoblockers. PMID- 1906121 TI - [Hemodynamic changes in patients with myocardial infarct complicated by acute left ventricular failure during combined nitroglycerin and dobutamine therapy]. AB - A total of 18 patients with acute myocardial infarction complicated by acute left ventricular failure were examined for their central hemodynamics. Intravenous nitroglycerin was shown to cause positive changes in central hemodynamic parameters, but it failed to normalize the hemodynamics in patients with baseline low blood pressure, as nitroglycerin induced a further reduction in blood pressure. A combined administration of nitroglycerin and dobutamine solutions contributes to hemodynamic normalization and is indicated for patients with acute myocardial infarction complicated by acute left ventricular failure at a baseline low blood pressure. PMID- 1906122 TI - [Use of laser-enzyme therapy in preparing purulent wounds for early plastic closure]. AB - The results of treatment of 370 patients with purulent soft tissue diseases have shown that laseroenzymotherapy of the suppurating wounds contributed to their rapid cleaning, maintenance of microbial colonization at a stable low level, activation of reparative processes. This permitted to prepare a wound surface for closure at the nearest days after the operation. PMID- 1906123 TI - [Complex treatment of rare giant malignant breast tumors]. PMID- 1906124 TI - [Changes in the microflora of burn wounds after local treatment]. PMID- 1906125 TI - Procedure for assessing the behavioral effects of novel anti-parkinsonian drugs in normal and MPTP-treated marmosets following central microinfusions. AB - Comparison between drug effects in MPTP- and non-MPTP-treated marmosets following intracerebroventricular (ICV) and intraputamen administration are given in the present report. Both side-effect profiles and the ability to reverse MPTP-induced hypokinesia were assessed using a variety of dopamine receptor agonists (quinpirole, PHNO, ADTN), cholinergic antagonists (scopolamine, secoverine, himbacine), a glutamate receptor antagonist (MK801) and a 5-HT receptor agonist (8-OH-DPAT). Our results show that direct infusion of agents into the putamen or via the ICV route can reverse parkinsonian-like symptoms in marmosets. Furthermore, chronic implantation of cannulae into the putamen or ventricles of nonhuman primates can be useful in assessing the therapeutic activity of agents that do not readily cross the blood-brain barrier. PMID- 1906126 TI - Saturation effects in phosphorus-31 magnetic resonance spectra of the human liver. AB - Phosphorus-31 liver spectra were recorded from 6 controls and 12 patients with liver disease using TR values of 0.5 and 5 s and a pulse angle of 45 degrees. One of the control subjects was also examined at seven TR values ranging from 0.5 to 20 s. Spectra from one additional patient were collected at TRs of 0.5, 1, and 2 s only. There was a significant increase in the mean ratio of peak areas phosphomonoesters (PME)/beta-ATP in 9 of the 13 patients and a decrease in phosphodiesters (PDE)/beta-ATP in 3 of the patients, compared with controls, at the longer TR values. The saturation factors for PME and PDE were greater than those for Pi and beta-ATP, and spectral abnormalities in disease were often more evident as the TR value was increased from 0.5 to 5 s. Acquisition parameters need to be chosen with a knowledge of the impact that saturation effects have on metabolite quantification and spectral contrast. PMID- 1906127 TI - Detection of antibodies to p24 and gp41 epitopes of HIV by ELISA using the recombinant core protein (p24) and envelope synthetic protein (gp41). AB - We have developed a system consisting of two separate ELISA, one designed to detect antibodies to HIV gag gene (p24) and the other to detect antibodies to HIV env gene (gp41). The antigen used in these ELISA was produced as recombinant DNA derived proteins expressed in E. coli for HIV gag gene (p24) and synthetic peptide for the HIV env gene (gp41). These HIV (env-gag) ELISA, that provide independent determinations of the antibody response to the core and envelope proteins, are highly specific and sensitive. In this work we have demonstrated that determinations of antibodies such as those to p24 and gp41 by HIV (env-gag) ELISA are among the criteria for a confirmation procedure, and sensitivity one (gp41) and/or both these determination should be equal or greater than the sensitivity of W.B. In addition, the procedure should be objective and standardized and the antigen source used should be different from that adopted in the "classical" W.B. and screening test. In view of these considerations, this HIV (env-gag) ELISA could be used as a reliable alternative to W.B. for confirmation of antibody detection. PMID- 1906128 TI - [The phenotypic study and numerical analysis of coryneform bacterial strains having a variation in peptidoglycan A4 gamma]. PMID- 1906129 TI - An improved method for the detection of differential survival between normal and xeroderma pigmentosum lymphoblastoid cell lines in culture with 4-nitroquinoline 1-oxide. AB - The effects of the UV-mimetic chemical 4-nitroquinoline-1-oxide (4-NQO) upon cell lines heterozygous or homozygous for the recessive mutant xeroderma pigmentosum (XP) were investigated. Human lymphoblastoid cell lines, which were established from 4 XP homozygote patients (XPL15, XPL17, XPL19 and XPL20). 2 XP heterozygote individuals (XPPL17 and XPML17) and 58 normal individuals, were cultured in the presence of 4-NQO at doses of 0, 2, 4 and 8 x 10(-6) M. Then the total cell number was counted and the viability of the cells was measured by the dye exclusion method using trypan blue and a newly devised fluorometric method with fluorescein diacetate. Results showed that 4-NQO affected, in increasing order of impairment, the cell lines: normal less than XP heterozygote less than XP homozygote. PMID- 1906130 TI - Differential repair of 1-beta-D-arabinofuranosylcytosine-detectable sites in DNA of human fibroblasts exposed to ultraviolet light and 4-nitroquinoline 1-oxide. AB - The extent of DNA excision repair was determined in dermal fibroblast strains from clinically normal and xeroderma pigmentosum (XP; complementation group A) human donors after single or combined exposures to 254-nm ultraviolet light and 4 nitroquinoline 1-oxide (4NQO). The repair was monitored by incubation of the treated cultures in the presence of 1-beta-D-arabinofuranosylcytosine (araC), a potent inhibitor of long-patch excision repair, followed by quantitation of araC accumulated DNA single-strand breaks (representing repair events) by velocity sedimentation analysis in alkaline sucrose gradients. The amount of repair in normal fibroblast strains increased as a function of UV fluence and reached a plateau at 15 J/m2; strand breaks were not detected when these same cultures were irradiated with as much as 60 J/m2 UV and incubated in the absence of araC, implying that an initial (incision) step is rate-limiting in the repair of UV damage. In normal fibroblasts (i) the incidence of araC-detectable lesions removed during fixed intervals following exposure to 4NQO (4 microM; 30 min) was approximately 2.5 times greater than that seen following irradiation with repair saturating fluences (greater than or equal to 15 J/m2) of UV-rays; and (ii) the amount of repair in cultures treated simultaneously with 4NQO (0.5-6 microM; 30 min) and a repair-saturating fluence of UV (20 J/m2) was found to approach the sum of that arising from exposure to each separately. The XP cells (XP12BE) exhibited a deficiency in the removal of araC-detectable DNA lesions following exposure to either of the carcinogens. Since araC is known to inhibit the repair of alkali-stable 4NQO-DNA adducts (i.e., lesions assumed to be removed by the UV like excision pathway) but not that of alkali-labile sites (i.e., DNA lesions operated on by the X-ray-like repair pathway), our results strongly imply that the multistep excision-repair pathway operative on UV photoproducts in human fibroblasts differs from that responsible for removing alkali-stable (araC detectable) 4NQO adducts by at least one step, presumably the rate-limiting incision reaction mediated by a lesion-recognizing endonuclease. PMID- 1906131 TI - Preferential repair of DNA damage on the transcribed strand of the human metallothionein genes requires RNA polymerase II. AB - To examine the possible role of transcription in directing repair of DNA damage in active genes, we compared repair of UV- and aflatoxin B1-induced damage on each strand of the human metallothionein (hMT) genes. Repair on the transcribed strand of an active hMT gene occurs at least 3 times faster than that on its nontranscribed strand. Both strands of inactive genes and both strands of a regulatory region 5' to an active gene are not repaired at this faster rate. Inducing higher levels of transcription with dexamethasone selectively increased the rate of repair on only the transcribed strand of the induced gene, while treatment of cells with alpha-amanitin eliminated the strand-selective repair. These results demonstrate that repair on the transcribed strand of a gene is independent of repair on the nontranscribed strand and that the transcriptional complex plays a role in directing repair to the transcribed strand of active genes. PMID- 1906132 TI - The use of EDTA-permeabilized E. coli cells as indicators of aflatoxin B1-induced differential lethality in the DNA repair host-mediated assay. PMID- 1906133 TI - Experimental mycetoma due to Streptomyces griseus in the laboratory mice. AB - A study was performed to investigate the ability of Streptomyces griseus to cause experimental mycetoma in the skin and in the foot pads of mice. The lesions appeared as palpable subcutaneous nodules discharging pale yellow cheesy pus and granules of S. griseus. The inoculated foot pads of the mice also developed nodular lesions which later became oedematous with bone destruction and fibrosis. PMID- 1906134 TI - Mycotoxin production on different cultivars and lines of broad bean (Vicia faba L.) seeds in Egypt. AB - One hundred different cultivars and lines of broad bean (Vicia faba L.) seed samples were inoculated with Aspergillus flavus Link (CMI 102135) to determine varietal differences which may support or resist aflatoxin production. Thin-layer chromatographic analysis of the chloroform extracts of the different seed samples revealed that 11 cultivars/lines were highly resistant to seed invasion and aflatoxin production while 9 cultivars/line showed partial resistance. The remaining 80 samples were susceptible to the establishment of A. flavus and aflatoxin accumulation. All the resistant cultivars/lines seed samples were inoculated also with three local isolates of fungi namely; Stachybotrys chartarum (Ehrenb. ex Link) Hughes, Aspergillus ochraceus Wilhelm, and Fusarium oxysporum Schlecht. The resistant seed samples were also resistant for colonization with these fungi and mycotoxin formation. PMID- 1906135 TI - Effect of low protein diet on chronic aflatoxin B1-induced liver injury in rhesus monkeys. PMID- 1906136 TI - Toxigenic Aspergillus flavus and aflatoxins in Sri Lankan medicinal plant material. AB - The fungal flora of 6 Asian medicinal plants, Aerva lanata (Linn.) Juss. Alyssicarpus vaginalis D.C., Tribulus terrestris Linn. Adhatoda vasica Nees., Centella asciatica (L.) Urb., Cardiospermum halicacabum Linn. was determined. After surface disinfection Aspergillus spp. were most frequently observed. Aspergillus flavus, isolated from Alyssicarpus vaginalis and Aerva lanata produced aflatoxins in culture. Aflatoxin B1 was also detected in a sample of Aerra lanata at a level of 0.5 micrograms/g. Plant material destined for medicinal use should be stored carefully prior to its use to prevent growth of naturally occurring toxigenic mold fungi. PMID- 1906137 TI - More views on Imanishi-Kari. PMID- 1906138 TI - Palaeoanthropology. Teeth, sex and species. PMID- 1906139 TI - Extreme sexual dimorphism in a Miocene hominoid. AB - Some Miocene hominoids may have been extremely sexually dimorphic for body size, inferred from the apparent dimorphism of dental and gnathic remains. But this has never been demonstrated convincingly for any fossil species because of small sample sizes, uncertainties about the number of species in most fossil samples, and the inability to reliably sex individual specimens. Here we demonstrate a case of extreme dental dimorphism, and presumed body-size dimorphism, in a Miocene hominoid sample in which these limitations have been overcome. Lufengpithecus lufengensis from the late Miocene site of Lufeng, China, was more dimorphic than the most dimorphic living hominoid, the orangutan, and may have been more dimorphic than any living anthropoid. PMID- 1906140 TI - v-Src and EJ Ras alleviate repression of c-Jun by a cell-specific inhibitor. AB - The AP-1 family of transcription factors, which includes the proto-oncogene products c-Jun and c-Fos, controls the stimulation of cellular genes by growth factors and the expression of oncogenes, including src and ras. Transcriptional activation by c-Jun is regulated by a cell-type-specific inhibitor that represses the activity of a transcriptional activation domain (A1) of c-Jun by operating through the adjacent negative regulatory region (delta). Here we show that cotransfection of the src or ras oncogene enhances the transcriptional activity of a GAL4:c-Jun hybrid that includes the delta-A1 region of c-Jun, suggesting that the DNA binding and dimerization domain of c-Jun is not required for stimulation by Src or Ras. Moreover, induction of c-Jun activity by Src and Ras occurs in cell lines containing the c-Jun inhibitor but not in a cell line lacking it. The region in c-Jun essential for the stimulatory action of these oncogenes maps to domain A1. These findings suggest the existence of signal transduction pathways that result in an increase in transcriptional activity of c Jun and AP-1 by disrupting the c-Jun:inhibitor interaction. PMID- 1906141 TI - [Fantasy and reality: fluvoxamine. International symposium, Fussen, 4 May 1991]. PMID- 1906142 TI - Prevention of vasospasm by clot removal and intrathecal bolus injection of tissue type plasminogen activator: preliminary report. AB - In this study, we evaluated the efficacy of postoperative intrathecal injections of tissue-type plasminogen activator (tPA) in preventing cerebral vasospasm in cases with a diffuse severe subarachnoid hemorrhage. All 10 cases were graded Group 3 according to the classification of Fisher and associates, and the CT number (Hounsfield number) of the subarachnoid clot was over 75. After clipping the aneurysm and removing the clot, three cisternal drainage catheters were inserted into both sylvian cisterns and the prepontine cistern, and continuous ventricular drainage was performed routinely. Postoperatively, tPA (0.5 mg/2.5 ml) was infused as a bolus into both basal cisterns and the lateral ventricle twice daily for about 6 days. Angiography and cerebral blood flow studies using single photon emission computed tomography were performed on Day 4 or 5 and between Days 7 and 10 after onset of the hemorrhage. To date, there have been no cases that have shown angiographic vasospasm or delayed ischemic neurological deficits. This preliminary study indicates that the intrathecal bolus injection of tPA produces a marked effect on vasospasm. PMID- 1906143 TI - Transoral decompression evaluated by cine-mode magnetic resonance imaging: a case of basilar impression accompanied by Chiari malformation. AB - Cine-mode magnetic resonance imaging provides simultaneous images of cerebrospinal fluid flow dynamics. A patient with a basilar impression accompanied by a Chiari malformation and von Recklinghausen's disease who underwent transoral decompression is reported. Preoperative cine-mode magnetic resonance imaging visualized an associated obstruction of cerebrospinal fluid pulsatile flow at the level of the foramen magnum. Tonsilar herniation (Chiari I malformation) and hydrocephalus were also present. Postoperatively, the obstruction of cerebrospinal fluid flow was resolved concomitant with the correction of the cervicomedullary angulation. On the basis of observations made by magnetic resonance imaging, the surgical treatment of basilar impression accompanied by Chiari malformation is briefly discussed. PMID- 1906144 TI - Subarachnoid hemorrhage from multiple neurofibromas of the cauda equina: case report. AB - The authors report a case of spinal subarachnoid hemorrhage caused by neurofibromas of the cauda equina. An examination of the literature revealing 13 similar cases and an analysis of this case showing three neurofibromas of the cauda equina prompted an hypothesis emphasizing the origin of bleeding and the difficulties associated with a correct diagnosis. PMID- 1906145 TI - An open trial of OKT3 in patients with multiple sclerosis. AB - We report our experience with treatment with Muromonab-CD3 (Orthoclone OKT3) of 16 patients with multiple sclerosis (MS) who were in a progressive phase of their disease (n = 13) or in an acute severe attack lasting longer than 1 month without recovery (n = 3). We induced acute severe T-cytopenia with OKT3. Fifteen patients completed treatment for 10 days. Side effects were common and severe and included hypotension, nausea and vomiting, diarrhea, fever, and myalgia. In two of two patients tested, there was a transient though major rise in the levels of interferon gamma and tumor necrosis factor in the first 12 hours of treatment. Nonetheless, we did not detect new clinical or MRI activity of MS during the period of treatment, although many patients deteriorated transiently in disability scores. At the conclusion of follow-up, only four patients had deteriorated by 1.0 or more points on the Expanded Disability Status Scale of Kurtzke (EDSS) (73% stabilization rate). Of those patients who deteriorated, two died of complications of MS (EDSS 10). Only two patients had clinical improvement at 1 year follow-up. The attendant toxicity of OKT3 makes it unlikely that it will play a major role in the treatment of MS. PMID- 1906146 TI - Localization of implanted dipoles by magnetoencephalography. AB - We attempted to validate the location of sources predicted by magnetoencephalography (MEG) by studying 19 specially designed dipole electrodes implanted in six patients with intractable partial seizures who were undergoing subdural electrode recording. We used a seven-channel magnetometer to measure the magnetic fields produced by passing through the dipoles a 40-microA, 5-msec square-wave pulse followed 40 msec later by a pulse of opposite polarity; 200 pulses were averaged for each magnetometer position. The actual dipole locations were measured from skull radiographs, and we based MEG localization on a spherical head model with the inclusion of volume currents. MEG estimates of the sources were within several centimeters (mean, 1.69 cm) of the measured locations. We conclude that MEG localization was promising. PMID- 1906147 TI - Modulation of MHC class II antigen expression in human myoblasts after treatment with IFN-gamma. AB - Some investigators have proposed myoblast transfer as a potential therapy for the treatment of Duchenne muscular dystrophy. Little is known about the immunobiology of myoblast transplantation. Transplantation rejection is mediated to a large extent by CD8+ T cells, which recognize alloantigens encoded by class I HLA genes, and by CD4+ T cells, which recognize alloantigens encoded by class II HLA genes. Gamma interferon (IFN-gamma) is a potent inducer of HLA class II molecules as well as beta 2-microglobulin, which is co-expressed with HLA class I. IFN gamma may be a critical cytokine involved in graft rejection. We purified human myoblasts by flow cytometry and incubated them in vitro for varying time periods with recombinant human IFN-gamma. The inducibility of HLA-DR and -DP molecules raises a note of caution concerning possible rejection phenomenon which might occur following myoblast transplantation. PMID- 1906148 TI - [Evaluation of esophageal function in surgically-treated patients]. AB - The authors report on their experience acquired in the surgical treatment of functional esophageal disease (achalasia, diffuse esophageal spasm, diverticula and gastroesophageal reflux). The authors affirm that a correct and meticulous functional study of the esophagus is fundamental for the adoption of precise surgical plotting, in order to circumvent all of the complications and failures described in Literature. Such an objective can be achieved intraoperatively thanks to myotomy and fundoplication with the aid of intraoperative manometry (IEM) that, when performed in the course of myotomy, circumvents the execution of incomplete procedures (incomplete myotomies). The same holds true in the case of anti-reflux plasty (Nissen's in particular) where IEM enables a plication that is neither too wide nor too narrow, too long, too short, but "calibrated". Then, instrumental probes are even more capable of assessing the effects of functional surgery, by enabling the documentation of perfect postoperative results. More precisely they make it possible to study patients presenting with motor disorders pre-operatively, as in the case of achalasia or diverticula, and to sanction their resolution postoperatively. In addition they enable documentation of the effectiveness of Nissen's fundoplication, performed either to prevent gastroesophageal reflux after myectomy or to treat primary reflux. This is made possible by studying not only the tone at a distance, but especially relaxation in the course of deglutition. Finally, pH-metry permits the documentation of the complete clearing of gastroesophageal reflux, even when physiologic and post prandial (hypercompetent Nissen). PMID- 1906149 TI - [Esophageal manometry and pH-monitoring: cost-benefit analysis]. AB - Functional tests of the esophagus have become increasingly popular over the last 10 years. Here we present a cost/benefit analysis model to evaluate the real contribution to diagnosis with reference to the cost of these tests. All of the patients referred to the digestive physiopathology laboratory at the Institute of Surgical Semiotics, from 1988 to 1990, were evaluated for gastroesophageal reflux disease (152 cases), dysphagia (27 cases) and chest pain (12 cases). The cost of each modified diagnosis was L. 508,250 in the first case, L. 315,772 in the second case and L. 262,446 in the third case. Additionally, concerning gastroesophageal reflux disease, the cost of medical therapy based on endoscopic diagnosis alone was compared to that of medical therapy guided by these functional tests. Hence it was demonstrated that it is economically advantageous to study functionally all of the symptomatic patients, except the cases of esophagitis, and patients with atypical symptoms or with mild symptoms and endoscopic esophagitis of the first degree. It is not worthwhile investigating patients with second, third or fourth degree esophagitis, regardless of the symptoms, and patients with typical severe symptoms and first degree esophagitis. These functional tests are economically practical in all cases in which morphologic alterations are either absent or minimal. PMID- 1906150 TI - [Ultrasonography in diseases of lymph nodes and soft tissues of the neck]. AB - A study of 55 patients affected by neoplasia of the head and neck or clinically evident laterocervical swellings was carried out in order to evaluate the diagnostic value of ultrasonography in the study of cervical lymph nodes and soft tissues, excluding thyroid or salivary pathologies. The analysis of results confirmed that, in line with previously published findings, ultrasonography is a reliable method of diagnosing lesions and correctly identifying the affected organ, but then it is considerably less reliable in defining the type of lesion. In view of this, it is reasonable to propose a more widespread use of ultrasonographically guided needle biopsy which, in addition to being a rapid and non-traumatic method, would allow precisely target samples to be taken from those lesions with a doubtful or unusual clinical or ultrasonic appearance. PMID- 1906151 TI - [Determination of free light chains in biological fluids by a latex test]. AB - A novel latex test for the detection and characterization of free light chains in different biological fluids is presented. Accuracy, reliability and sensitivity of the method are evaluated, by comparing experimental results with reference techniques for light chain detection. The assay is tested for quickness and easiness, in order to be routinely used in laboratories of Clinical Chemistry, Haematology, Nephrology and Radiology. PMID- 1906152 TI - Adjunctive leuprolide therapy does not improve cycle fecundity in controlled ovarian hyperstimulation and intrauterine insemination of subfertile women. AB - Problems arising from controlled ovarian hyperstimulation for intrauterine insemination, such as premature luteinization and asynchronous ovarian follicular development, are identical to those encountered with controlled ovarian hyperstimulation for in vitro fertilization (IVF) and gamete intrafallopian transfer (GIFT). It has been suggested that the adjunctive use of GnRH agonists for controlled ovarian hyperstimulation improves the efficiency of GIFT and IVF cycles. We hypothesized that adjunctive use of leuprolide acetate, a GnRH agonist, would have a similarly beneficial effect on cycle quality and cycle fecundity in subfertile women treated with controlled ovarian hyperstimulation and intrauterine insemination. We randomly assigned the first cycle of controlled ovarian hyperstimulation and intrauterine insemination for each of 97 subfertile women to include either human menopausal gonadotropins (hMGs) alone or hMGs following midluteal pre-treatment with leuprolide. If a pregnancy did not occur in the first cycle, the woman was given the other treatment in the second cycle. Although the cycles that included leuprolide required a larger amount of hMGs and more days of stimulation per cycle, the mean estradiol concentrations and numbers of follicles were not different. Despite prevention of premature luteinization with leuprolide, the cycle fecundity was not different between groups (0.11 with adjunctive leuprolide treatment and 0.22 with hMGs alone). We conclude that in unselected subfertile patients, the adjunctive use of leuprolide for controlled ovarian hyperstimulation and intrauterine insemination does not improve cycle fecundity compared with treatment cycles that do not include adjunctive leuprolide therapy. PMID- 1906153 TI - [First experiences with intraperitoneal chemotherapy]. AB - Four patients suffering from malignant ascites were treated with the following method: peritoneal lavage and consequent injection of Mitomycin-C (20 mg/body surface m2) was performed for six hours via a catheter put into the peritoneal cavity according to Seldinger's method. One patient died three weeks later because of involvement of other organs by the disease. The other patients have been followed-up ever since for 7, 4 and 3 months now. In their case there was no need for repeated intraperitoneal chemotherapy. There were no side-effects nor complications detected. PMID- 1906154 TI - Modulation of platelet-derived growth factor A- and B-chain/c-sis mRNA by tumor necrosis factor and other agents in adenocarcinoma cells. AB - Human Platelet Derived Growth Factors (PDGF) are potent mitogens for mesenchymal cells and encoded by two related genes, the A- (or 1-) and B- (or 2-) chain. The latter is known as the human homolog (c-sis) of the v-sis oncogene. We investigated the expression and cytokine-mediated regulation of PDGF A- and B chain mRNA in endoderm-derived cells, i.e. cultured human pancreatic adenocarcinoma cells. Northern blot analysis revealed that out of 14 cells lines 11 were positive for the A-chain and 10 for the B-chain. Tumor Necrosis Factor (TNF) -alpha and -beta, but not Interferon (IFN) -gamma, drastically upregulate the mRNA levels for PDGF B-chain and for the A-chain in a dose-dependent manner in nearly every pancreatic tumor cell line investigated (n = 6). With respect to the signal pathway stimulated by TNF, no evidence emerged for an activation of protein kinase A. The inhibition of protein kinase C by staurosporine (in the absence or presence of TNF) as well as its stimulation by PMA resulted in an increased mRNA level for the B-chain, indicating a functional role of PKC in this system. Furthermore, time course experiments and Cycloheximide treatment showed that the A- and B-chain mRNA are regulated by different mechanisms in transformed epithelial cells. Irrespective of these differences, the sum of their biological functions may contribute to the phenomenon of desmoplasia in pancreatic tumors by epithelial/mesenchymal interactions. PMID- 1906155 TI - HTLV-1 Tax induces expression of various immediate early serum responsive genes. AB - Human T-cell leukemia virus type 1 (HTLV-1) is an etiological agent of adult T cell leukemia (ATL). We showed here by mobility-shift assay that T-cell lines transformed with the virus contained high levels of AP-1 activities. Consistent with this result, these cell lines expressed increased levels of mRNAs encoding the AP-1 proteins, c-Fos, Fra-1, c-Jun, JunB, and JunD. Previously, transcription of the c-fos gene has been reported to be transactivated by the viral transcription factor, Tax1. By using the human T-cell line (JPX-9), in which expression of the Tax1 is inducible, we showed that expression of mRNAs for Fra 1, c-Jun, and JunD was also transactivated by Tax1. Moreover, Tax1 activated expression of two other transcription factors having zinc finger motifs, Egr-1 and Egr-2, in the same cells. The Tax1-inducible transcription factors identified here are encoded by the members of immediate early genes under the control of growth signals. Thus, Tax1 was suggested to replace growth signals, at least in part, by this mechanism. PMID- 1906156 TI - Tyrosine phosphorylation of GAP and GAP-associated proteins in lymphoid and fibroblast cells expressing lck. AB - The Ras GTPase activating protein (GAP) is a strong candidate for the protein that links protein-tyrosine kinases to the Ras mitogenic pathway. GAP and two associated proteins, p62 and p190, were shown to be phosphorylated on tyrosine in the LSTRA thymoma cell line, in which the p56lck tyrosine kinase is overexpressed as a result of retroviral promoter insertion. In NIH3T3 fibroblasts expressing specific oncogenic and transformation-defective variants of p56lck, we found that the tyrosine phosphorylation of GAP complexes required both enzymatic activation and myristylation of p56lck, and correlated with lck transforming activity. The interaction between p62 and p190 from lck-transformed fibroblasts and GAP could be reconstituted in vitro using bacterial TrpE fusion proteins containing GAP Src homology 2 (SH2) domains. In vitro complex formation was insensitive to the prior denaturation of SH2 ligands, suggesting that SH2-binding sites are formed by linear peptide sequences. These results suggest that the tyrosine phosphorylation of GAP, and its interactions with SH2-binding proteins, may be involved in fibroblast transformation by activated lck, and may participate in signal transduction and cellular transformation in lymphoid cells. PMID- 1906157 TI - Suppression of c-myc and c-myb is tightly linked to terminal differentiation induced by IL6 or LIF and not growth inhibition in myeloid leukemia cells. AB - Cell proliferation and differentiation are intimately related processes where the proto-oncogenes c-myc and c-myb have been implicated to play a role. Previously, we have shown that both c-myc and c-myb were induced in normal myeloid precursors when the cells were stimulated for growth, were expressed in the autonomously proliferating myeloid leukemic M1 cell line and were rapidly suppressed in both normal and M1 cells following induction of terminal differentiation associated with growth arrest. In order to distinguish molecular events associated with terminal differentiation versus those due to growth inhibition, as well as to increase our understanding of the role of the proto-oncogenes c-myc and c-myb in both of these cellular processes, in this work we have studied the expression of c-myc and c-myb in M1 cells induced for growth inhibition associated with terminal differentiation (via treatment with the physiological inducers IL6 or leukemia inhibitory factor mean value of LIF), partial differentiation (using IL1 or LPS) or no detectable differentiation properties (using IFN beta or IFN gamma). We show that, for all the treatments used in this study, down regulation of the proto-oncogenes c-myc and c-myb occurred only when M1 cells were stimulated to undergo terminal differentiation. In addition, we transfected the M1 cell line with a vector containing the c-myc gene under control of the beta actin promoter, so that c-myc was no longer down regulated by IL6 or LIF. Previously, we have shown that in the presence of the myeloid differentiation inducers IL6 or LIF, these M1myc cells were blocked at an intermediate stage of myeloid differentiation and continued to proliferate. In sharp contrast to their altered response to IL6 or LIF, M1myc cells were as responsive as the parental M1 cells to growth suppression by the different antiproliferative compounds which do not induce terminal differentiation. Thus, continued expression of c-myc had no effect on growth suppression induced by IL1, IFN beta, IFN gamma and LPS. Taken together, these results indicate that c-myc and c-myb down regulation is not necessary for growth suppression, but down regulation of c-myc is, and c-myb may be, essential for terminal differentiation. PMID- 1906158 TI - Co-regulated expression of junB and MHC class I genes in adenovirus-transformed cells. AB - The expression of the junB gene parallels the expression of the MHC class I genes in Adenovirus (Ad) transformed cells. In Ad12E1-transformed primary BRK cells both genes are transcriptionally repressed only when the 13S product of Ad12E1A is present. This indicates that repression of MHC class I and junB genes is a function of conserved region 3 (CR3) of the Ad12E1A protein. In Ad5-transformed BRK cells expression of these genes is unchanged. In established NRK cells, however, introduction of Ad12E1A does not cause repression of the MHC class I and junB genes, but in these cells Ad5E1A increases the expression of both MHC class I and junB. Using mutant Ad5E1A genes, it is shown that this activation is mediated by CR1. Introduction of a functional junB gene under the control of a heterologous promoter in Ad12E1-transformed BRK cells causes no increase in MHC class I expression. This demonstrates that the down-regulation of junB is not directly responsible for class I repression, but rather that both genes are coregulated by the Ad12E1 region. PMID- 1906159 TI - EGR3, a novel member of the Egr family of genes encoding immediate-early transcription factors. AB - We have previously described two cellular immediate-early genes, Egr-1 (mouse) and EGR2 (human) that encode zinc finger proteins. Here we report the characterization of a new member of the Egr family referred to as EGR3 (human). This cDNA clone was isolated using low stringency hybridization with the zinc finger domain of Egr-1. The EGR3 cDNA sequence predicts a 387 amino acid (a.a.) protein containing three Cys2-His2 zinc fingers nearly identical to those of Egr 1 and EGR2. This similarity has a functional consequence: EGR3 can activate transcription of a CAT gene linked to the sequence CGCCCCCGC, a cis element which is a target for Egr-1 and EGR2. We show that EGR3 is an immediate-early growth response gene induced by mitogenic stimulation of rodent and human fibroblasts and a monkey kidney epithelial cell line. The EGR3 gene has a single intron and maps to chromosome 8 at bands p21-23. PMID- 1906160 TI - Comparative trial of cefprozil vs. amoxicillin clavulanate potassium in the treatment of children with acute otitis media with effusion. AB - A total of 137 children with acute otitis media with effusion were randomly allocated to treatment with cefprozil (30 mg/kg/day divided into two equal doses), an investigational cephalosporin or amoxicillin clavulanate potassium (40 mg/kg/day divided into three equal doses) for 10 days. The most common pathogens obtained from middle ear cavities by tympanocentesis were Streptococcus pneumoniae (33%), Haemophilus influenzae (19.6%) and Moraxella catarrhalis (8.3%). Patients were scheduled for follow-up visits at midtreatment, at end of therapy and at 30 days. Of the 137 children 122 were evaluable. Five of 60 patients (8.3%) treated with cefprozil and 14 of 62 patients (22.5%) treated with amoxicillin clavulanate potassium were considered therapeutic failures because of persistence of symptoms and/or isolation of the original pathogen or superinfection (P = 0.05). Rates of relapse, reinfection and persistent middle ear effusion as documented by tympanogram were comparable in both groups. When persistent middle ear effusion was analyzed by pneumatic otoscopy, 64 of 103 affected ears (62.1%) treated with cefprozil and 80 of 105 affected ears (76.1%) treated with amoxicillin clavulanate potassium were abnormal (P = 0.04). Loose stools were more common in children treated with amoxicillin clavulanate potassium than in children treated with cefprozil (P = 0.0004). Based on the efficacy results from this study, the lower gastrointestinal side effects and the convenience of twice-a-day dosing, we believe that cefprozil in a dosage of 30 mg/kg/day divided every 12 hours represents a potential alternative for the treatment of acute otitis media with effusion in children. PMID- 1906161 TI - Comparison of 6 and 8 hourly tobramycin dosing intervals in treatment of pulmonary exacerbations in cystic fibrosis patients. AB - The efficacy and toxicity of a shortened tobramycin dosing interval in the treatment of exacerbations of Pseudomonas aeruginosa pulmonary infection in cystic fibrosis patients were evaluated prospectively. Patients ages 13 to 30 years received 34 treatment courses and were randomized by pairs to receive tobramycin administered either every 6 or 8 hours. Peak serum concentrations were adjusted to 8 to 10 micrograms/ml; thus a larger total daily dosage was administered to patients receiving tobramycin every 6 hours. The shorter dosing interval was associated with better pulmonary function at follow-up and significantly longer time before next hospital admission for a pulmonary exacerbation. During the study hospitalization there were no differences in pulmonary function tests, clinical score, sputum carriage of P. aeruginosa, toxicity or necessary length of hospitalization. A 6-hour tobramycin dosing interval was more efficacious than an 8-hour dosing interval in the treatment of cystic fibrosis patients. PMID- 1906162 TI - [Two types of reactions of somatotropic hormone to the thyrolyberin administration in adolescents with euthyroid enlargement of thyroid gland]. PMID- 1906163 TI - [Diagnosis and therapy of mucopolysaccharidosis in children]. PMID- 1906164 TI - Institutional yield on research: a case study. AB - This University of Pennsylvania School of Nursing study on the early discharge of very low birthweight infants led to a care model that saves over $18,000 per infant. The benefits to the institution as a whole, however, have been far greater. They include enhanced faculty and student recruitment as well as $700,000 in indirect cost recovery. PMID- 1906165 TI - Long-term biopsychosocial effects of interleukin-2 therapy. AB - This three-year project evaluates the biopsychosocial effects of interleukin-2 (IL-2) therapy on the first 45 patients treated with the therapy at the Moses Division of the Montefiore Medical Center in Bronx, NY, starting in April 1986. Therapy with IL-2 and lymphokine-activated killer (LAK) cells is a promising new development but requires an extensive amount of supportive care. Various important issues must be considered in planning the care of patients being treated with IL-2, including the effects of the treatment on quality of life, the cost of resources necessary for providing therapy, and the emotional effects of treatments. The instruments used to measure the various aspects of quality of life were the Sickness Impact Profile, the Inventory of Current Concerns, the Symptom Distress Scale, the Acute Physiology and Chronic Health Evaluation Scale, and the Therapeutic Intervention Scoring System. The researchers believe that, in addition to tumor response, the biopsychosocial and financial effects of treatment should be understood. PMID- 1906166 TI - Case report: topical DMSO for mitomycin-C-induced skin ulceration. AB - Mitomycin-C is a commonly used anticancer drug for patients with advanced anal, breast, colorectal, gastric, lung, or pancreatic cancers. Mitomycin-C can cause severe necrosis and ulceration when extravasated inadvertently into skin and soft tissues following IV drug administration. Local applications of heat, ice, and common antidotes such as glucocorticosteroids and hyaluronidase or sodium thiosulfate have failed to reduce the experimental toxicity of these vesicant reactions in mice. Plastic surgery with split-thickness skin grafting may be required to palliate local pain symptoms and loss of function, although some extravasations heal without any local treatment. This brief communication summarizes two case reports of the treatment of severe mitomycin-C venous extravasations using topical applications of dimethylsulfoxide (DMSO). Although the authors' experience represents the results of DMSO interventions in only two patients, the response to treatment in both patients was so pronounced that others may find this useful in their practice. PMID- 1906167 TI - Economics of hospice care. AB - As an institution providing care for patients who are dying, hospice has expanded significantly since the opening of the first hospice in the United States in 1974. Many changes have occurred in that time, including the maturation of hospices and the introduction of third-party reimbursement under Medicare. This article examines literature on hospice from an economic perspective; the focus is on the characteristics of the hospice "industry," demand for hospice care, hospice as a supplier of care, and the cost of hospice care. Two major gaps in the research are the failure to categorize hospices by the type of reimbursement received and the emphasis on expenditures for care to the exclusion of consideration of the cost of producing hospice care. PMID- 1906168 TI - Radiation-induced inframammary moist desquamation. PMID- 1906169 TI - Variation of quantitative and qualitative changes of enchondral ossification in heterozygous achondroplasia. AB - Whereas the radiologic features of achondroplasia--the most common type of skeletal dysplasia in adults--are clearly defined there is still some debate about the severity and the type of histologic changes. Earlier descriptions reported severe disturbance of enchondral ossification to be typical of achondroplasia: They are, however, misleading by dealing mostly with cases of lethal neonatal dwarfism (e.g. thanatophoric dysplasia). Newer findings confirmed that only minor, quantitative lesions are typical of heterozygous achondroplasia. But even in recent years some observers noted more severe changes of enchondral ossification. An extensive histologic skeletal survey in a newborn achondroplastic male revealed remarkable findings: It clearly showed that in addition to a generalized, but moderate narrowing of the zones of enchondral ossification focal severe changes were present in various epiphyseal plates including clusterlike arrangement of enlarged chondrocytes, vacuolization, premature calcification and important fibrosis of cartilagineous matrix with membranous ossification. Our findings thus enable us to reconcile the seemingly divergent statements made before. PMID- 1906170 TI - Percutaneous endoscopic gastrostomy in elderly patients. AB - Percutaneous endoscopic gastrostomy (PEG) was performed on 28 elderly patients (mean age 82 years) who were dysphagic and intolerant of naso-gastric feeding. Twenty-six patients were recovering from a stroke; the interval between the onset of stroke and PEG averaged 63 days. The procedure was successful and well tolerated by all patients. Nineteen (68%) still had a functioning PEG a median of 14 weeks after placement. One patient whose swallowing recovered had the tube removed 6 months after its insertion. Seven patients (25%) subsequently died from their underlying disease, a mean of 92 days following PEG. There was one procedure-related death from peritonitis. PEG is a useful alternative to surgical gastrostomy in selected elderly patients with dysphagia who are intolerant of naso-gastric feeding. PMID- 1906171 TI - Afferent vagal fibres and central cholinergic mechanisms are involved in the TRH induced reversal of haemorrhagic shock. AB - In a model of haemorrhagic shock causing the death of all saline-treated rats within 25.8 +/- 2.7 min after treatment, the intravenous injection of thyrotropin releasing hormone tartrate (TRH-T) at the dose of 4 mg/kg induces a prompt and sustained increase of arterial pressure and pulse amplitude, with survival of all rats. Bilateral vagotomy, atropine sulphate (2 mg/kg intraperitoneally) and hemicholinium-3 (20 micrograms/rat intracerebroventricularly) partially prevent the TRH-T-induced shock reversal, whereas atropine methylbromide has no effect. These data indicate that afferent vagal fibres, brain cholinergic neurons and central muscarinic receptors play a role in the mechanism of the anti-shock effect of TRH-T. PMID- 1906172 TI - Diuretic and natriuretic effects of sorbinil, an aldose reductase inhibitor. AB - The renal effects of sorbinil, an aldose reductase inhibitor that interferes with the conversion of glucose to sorbitol, were studied in rats and rabbits before and after fluid deprivation. The intracellular osmolar solute, sorbitol, is found in increasing concentrations from cortex to medulla in the kidney and may be involved in the urinary concentrating mechanism. Oral administration of sorbinil in the rabbit resulted in significant increases in urine flow rate and sodium excretion with a tendency toward decreased urine osmolality and increased potassium excretion both before and after water deprivation. When fluid intake was controlled in the rat study, significant increases in urine flow rate and sodium and potassium excretion and a significant decrease in urine osmolality occurred only in response to fluid deprivation. Thus, sorbinil has diuretic and natriuretic properties and may prevent the normal concentration of urine in the antidiuretic animal. PMID- 1906173 TI - Carbachol-activated muscarinic (M1 and M3) receptors transfected into Chinese hamster ovary cells inhibit trafficking of endosomes. AB - We examined the effects of isoproterenol and carbachol on fluid-phase endocytosis by Chinese hamster ovary (CHO) cells transfected with beta-adrenergic, M1, or M3 cholinergic receptors. Isoproterenol increased cAMP production and carbachol increased intracellular Ca, indicating successful expression of the receptor genes and coupling to typical signal transduction pathways. Carbachol inhibited the uptake of horseradish peroxidase (HRP) or Lucifer yellow (markers of fluid phase endocytosis) in both M1- and M3-containing cells but not in wild-type cells, whereas isoproterenol did not affect pinocytosis in cells transfected with beta-adrenergic receptors. Carbachol inhibited the transit of HRP from an exchangeable pool to a nonexchangeable pool by a latent process requiring minimally 5 min of incubation. During the latent period, only one peak of low density HRP-containing vesicles was found on Percoll gradients; after 5 min, HRP appeared in both high- and low-density vesicles. Carbachol-treated cells contained less HRP in the high-density fraction enriched in lysosomal markers. Early endosomes from CHO cells labeled for 5 min with HRP underwent fusion to make a more dense population of vesicles in the presence of ATP and KCl at 37 degrees C but not at 4 degrees C. The fused material contained increased levels of G proteins as detected either by ADP ribosylation with appropriate toxins or by immunoblotting with specific antibodies. These findings suggest that GTP binding proteins are internalized in endocytic vesicles and enter into a complex trafficking process involving fusion with other vesicular compartments. Trafficking of endosomes to these compartments is inhibited by activated M1 and M3 muscarinic receptors in CHO cells. PMID- 1906174 TI - Human chromosome 16 encodes a factor involved in induction of class II major histocompatibility antigens by interferon gamma. AB - Interferon gamma (IFN-gamma) induces expression of class II major histocompatibility complex (MHC)-encoded antigens in immunocompetent cells. To gain further insight into the mechanism of this induction, we prepared somatic cell hybrids between different human cell lines and a murine cell line, RAG, that does not express murine class II MHC antigens before or after treatment with murine IFN-gamma. Some of the resulting cell hybrids express murine class II MHC antigens when treated with murine IFN-gamma. This inducible phenotype is correlated with the presence of human chromosome 16. It has been shown previously that the induction of class I MHC antigens by human IFN-gamma in human-rodent hybrids requires the presence of species-specific factors encoded by chromosome 6, which bears the gene for the human IFN-gamma receptor, and chromosome 21, whose product(s) is necessary for the transduction of human IFN-gamma signals. In this report, we show that the induction of murine class II MHC antigens by human IFN-gamma in the human-RAG cell hybrids requires, likewise, the presence of human chromosomes 6 and 21, in addition to chromosome 16. In some of these hybrids, when all three of these human chromosomes were present, induction of cell-surface HLA-DR antigens was also observed. Our results demonstrate that human chromosome 16 encodes a non-species-specific factor involved in the induction of class II MHC antigens by IFN-gamma. PMID- 1906175 TI - Molecular structure of Bacillus subtilis aspartate transcarbamoylase at 3.0 A resolution. AB - The three-dimensional structure of Bacillus subtilis aspartate transcarbamoylase (ATCase; aspartate carbamoyltransferase; carbamoyl-phosphate:L-aspartate carbamoyltransferase, EC 2.1.3.2) has been solved by the molecular replacement method at 3.0 A resolution and refined to a crystallographic R factor of 0.19. The enzyme crystallizes in the space group C2 with unit cell dimensions a = 258.5, b = 153.2, and c = 51.9 A and beta = 97.7 degrees. The asymmetric unit is composed of three monomers related by noncrystallographic threefold symmetry. A total of 295 of 304 amino acid residues have been built into the monomer. The last 9 residues in the C terminus were not included in the final model. Each monomer consists of 34% alpha-helix and 18% beta-strand. Three solvent-exposed loop regions (residues 69-84, 178-191, and 212-229) are not well defined in terms of electron density. The catalytic trimer of ATCase from B. subtilis shows great similarity to the catalytic trimer in Escherichia coli ATCase, which was used in constructing the model for molecular replacement. The unliganded trimer from B. subtilis, which is not cooperative, resembles the T (inactive) state slightly more than the R (active)-state form of the E. coli trimer. However, certain regions in the B. subtilis trimer exhibit shifts toward the E. coli R-state conformation. PMID- 1906176 TI - C terminus of the small GTP-binding protein smg p25A contains two geranylgeranylated cysteine residues and a methyl ester. AB - smg p25A, also known as the rab3A protein, is a small GTP-binding protein that has been implicated in intracellular vesicle transport and the secretion of neurotransmitters. It has been shown to bind reversibly to membranes, though its cDNA-predicted sequence contains no obvious membrane-binding domains. However, smg p25A does contain a cDNA-predicted C-terminal Cys-Ala-Cys sequence at positions 218 through 220, which suggests that it may be posttranslationally modified. In the present study we used two different approaches to investigate this possibility. First, we incubated pheochromocytoma cells with [3H]mevalonolactone, examined the proteins that became labeled by two-dimensional gel electrophoresis, and demonstrated that two of these proteins exactly corresponded to smg p25A. Second, we purified smg p25A from bovine brain membranes and analyzed both the full-length protein and a proteolytically derived C-terminal peptide by a combination of high performance liquid chromatography and mass spectrometry. This approach revealed that the protein's C-terminal region is methyl-esterified and contains two geranylgeranyl groups linked via thioether bonds to Cys-218 and Cys-220. Since smg p25A is one of several small GTP-binding proteins that share a C-terminal Cys-Xaa-Cys consensus sequence (where Xaa is an unspecified amino acid), our results suggest that these proteins may be similarly geranylgeranylated and methyl-esterified. PMID- 1906177 TI - Normal pre-B cells express a receptor complex of mu heavy chains and surrogate light-chain proteins. AB - Precursors of B cells, which constitute a subpopulation of the lymphocytes in bone marrow, can be identified by their surface expression of nonimmunoglobulin markers and the absence of immunoglobulin kappa and lambda light chains. Most pre B cells synthesize mu heavy chains but, without light-chain partners, these undergo rapid cytoplasmic degradation. In the present study, we demonstrate that late stage pre-B cells, like their neoplastic counterparts, express low levels of a surface receptor composed of mu chains paired with a surrogate light-chain complex formed by Vpre-B and lambda 5-like proteins. The data define a previously suspected but unrecognized stage in normal pre-B-cell differentiation. Expression of a clonally diverse receptor renders this population of immature B-lineage cells potentially vulnerable to clonal selection by antigens and idiotypic interactions. PMID- 1906178 TI - The small GTP-binding protein rab4 is associated with early endosomes. AB - Small GTP-binding proteins of the rab family have been implicated as playing important roles in controlling membrane traffic on the biosynthetic and endocytic pathways. We demonstrate that a distinct rab protein, rab4p, is associated with the population of early endosomes involved in transferrin-receptor recycling. An antibody to human rab4p was found to detect a doublet of approximately 24-kDa proteins on immunoblots from various cell types. Seventy-five percent of these proteins were tightly membrane bound and could be released only by detergent treatment. Upon isolation of early endosomes, late endosomes, and lysosomes, by free-flow electrophoresis and Percoll density-gradient centrifugation, most (70%) of the rab4p was found to cofractionate with early endosomes and endocytic vesicles containing 125I-labeled transferrin. The rab proteins previously localized to the endoplasmic reticulum and/or Golgi apparatus were not found in these fractions. We also localized rab4p to transferrin-receptor-containing early endosomes by immunofluorescence after expression of rab4 cDNA. The association of rab4p with early endosomes and other vesicles involved in the intracellular transport of transferrin receptor suggests that rab4p may play a role in regulating the pathway of receptor recycling. PMID- 1906180 TI - Hepatic and renal conjugation (Phase II) enzyme activities in young adult, middle aged, and senescent male Sprague-Dawley rats. AB - Acetaminophen (APAP)-induced nephrotoxicity is age dependent in male Sprague Dawley rats: nephrotoxicity occurs at lower dosages of APAP in 12- to 14-month olds compared with 2- to 3-month olds. The mechanisms responsible for enhanced nephrotoxicity in 12-month-old Sprague-Dawley rats are not entirely clear, but may be related to age-dependent differences in APAP metabolism in liver and/or kidney. Major pathways of hepatic APAP metabolism include sulfation and glucuronidation; glutathione conjugation represents a pathway for detoxification of reactive oxidative APAP metabolites. The present studies were designed to quantify in vitro activity of three Phase II enzyme activities: glutathione S transferase using 1-chloro-2,4-dinitrobenzene as substrate, UDP-glucuronyl transferase using APAP as substrate, and sulfotransferase using APAP as substrate, in subcellular fractions of liver and kidney of 3-, 12-, 18-, and 30 month-old naive male Sprague-Dawley rats. In liver, glutathione S-transferase, UDP glucuronyl transferase, and sulfotransferase activities were not significantly different in rats from 3 through 30 months of age. Renal UDP glucuronyl transferase and sulfotransferase activities were similar in rats from 3 through 30 months of age. In contrast, renal glutathione S-transferase activity was characterized by a lower Km in 12- and 30-month olds when compared with 3 month olds. These data suggest that the reduced total systemic clearance of APAP in 12-month-old male Sprague-Dawley rats previously observed cannot be attributed to age-dependent differences in hepatic APAP metabolism. In addition, it is unlikely that differences in renal APAP metabolism contribute to age-dependent APAP nephrotoxicity. PMID- 1906179 TI - Expression of von Willebrand factor "Normandy": an autosomal mutation that mimics hemophilia A. AB - von Willebrand disease Normandy (vWD Normandy) is a recently described phenotype in which a mutant von Willebrand factor (vWF) appears structurally and functionally normal except that it does not bind to blood coagulation factor VIII. This interaction is required for normal survival of factor VIII in the circulation; consequently, vWD Normandy can present as apparent hemophilia A but with autosomal recessive rather than X chromosome-linked inheritance. A vWF missense mutation, Thr28----Met, was identified in the propositus in or near the factor VIII binding site. The corresponding mutant recombinant vWF(T28M) formed normal multimers and had normal ristocetin cofactor activity. However, vWF(T28M) exhibited the same defect in factor VIII binding as natural vWF Normandy, confirming that this mutation causes the vWD Normandy phenotype. The distinction between hemophilia A and vWD Normandy is clinically important and should be considered in families affected by apparent mild hemophilia A that fail to show strict X chromosome-linked inheritance and, particularly, in potential female carriers with low factor VIII levels attributed to extreme lyonization. PMID- 1906181 TI - Acute renal function in chronically sympathectomized deoxycorticosterone acetate treated miniature swine. AB - We recently validated a swine model in which chronic treatment with 6 hydroxydopamine (6-OHDA) produced an effective sympathectomy. These sympathectomized swine demonstrated a significantly attenuated hypertensive response when treated with deoxycorticosterone acetate (DOCA). Because renal nerve activity is elevated and important in controlling renal function and blood pressure in the DOCA swine model, we wanted to study the effect of chronic sympathectomy on acute renal hemodynamics and tubular function. Kidney function was assessed in 14 DOCA-treated miniature swine, 8 of which were sympathectomized by chronic treatment with 6-OHDA, while 6 served as controls. Effective renal sympathectomy in this model has been previously confirmed by a significant reduction (97%) of norepinephrine in renal cortical tissue. When anesthetized, mean arterial pressure and renal blood flow were similar between the two groups. Glomerular filtration rate was lower by 43%, urine flow rate by 71%, sodium excretion by 66%, and potassium excretion by 48% in the 6-OHDA DOCA animals. All of these parameters were significantly different from the intact DOCA controls. These results indicate that anesthetized, chronically sympathectomized swine exhibit decreased renal excretory function. The changes in renal function may have been due to the development of a tubular or glomerular supersensitivity to circulating antinatriuretic factors, since the 6-OHDA group had a 28% greater pressor response to the alpha-agonist phenylephrine and a significantly greater fall in mean arterial pressure in response to alpha-blockade with prazosin when compared with the controls. These changes in renal function may also explain why the 6-OHDA animals demonstrated a slight increase in mean arterial pressure in response to DOCA. Because acute renal denervation in DOCA-treated swine produces a diuresis and natriuresis, this study affirms that there may be important functional differences in acutely versus chronically denervated kidneys for which the implications under normal physiologic conditions are unknown. PMID- 1906182 TI - Further evidence for the inhibitory action of baclofen on a prolactin-releasing factor. AB - The mechanism of action of a specific gamma-aminobutyric acid B receptor agonist, beta-p-chlorophenyl-gamma-aminobutyric acid or baclofen, in its inhibitory action on prolactin release, was studied. Dose-response studies of the effect of baclofen on prolactin (PRL) secretion were performed in stressed male rats. Furthermore, the action of the drug was evaluated in (i) rats treated with haloperidol or alpha-methyl-p-tyrosine, (ii) stressed or suckled rats pretreated with sulpiride, and (iii) animals treated with serotonin, alone, or with alpha methyl-p-tyrosine. Baclofen showed a clear dose-dependent inhibition of prolactin secretion in males under stress. The drug was unable to inhibit the prolactin release induced by haloperidol or alpha-methyl-p-tyrosine, although it reduced the PRL secretion induced by serotonin. It also inhibited PRL release in sulpiride-pretreated stressed or suckled rats. These results suggest that the dose-dependent effect of baclofen on PRL secretion is the consequence of an inhibition exerted on the prolactin-releasing factor component of the neuroendocrine responses evoked by stress or suckling, possibly acting at the serotonergic system. PMID- 1906183 TI - Nerve growth factor-induced differentiation of human neuroblastoma cell lines. PMID- 1906184 TI - The role of interferon-gamma in the immunotherapy of neuroblastoma. PMID- 1906185 TI - Natural interleukin-2 and lymphokine activated killer cells in the treatment of neuroblastoma in vitro and in vivo. PMID- 1906186 TI - Naloxone and serotonin receptor subtype antagonists: interactive effects upon deprivation-induced intake. AB - Whereas opiate receptor antagonists generally act to inhibit food intake under a variety of physiological conditions in rats, agonists of some serotonin (5-HT) receptor subtypes appear to stimulate intake, and others appear to inhibit intake. The present study evaluated the effects of the general 5-HT receptor antagonist, methysergide (1-5 mg/kg), the 5-HT2 receptor antagonists, ketanserin (1-2.5 mg/kg) and ritanserin (1-2.5 mg/kg), and the 5-HT3 receptor antagonist, ICS 205930 (1-5 mg/kg) upon deprivation (24 h)-induced intake themselves, and upon the hypophagic properties of the general opiate receptor antagonist, naloxone (1-5 mg/kg). Whereas the high doses of methysergide (0.5-4 h, 34%) and ketanserin (0.5 h, 28%) significantly decreased deprivation-induced intake themselves, ritanserin and ICS 205930 were without effect. Naloxone produced dose dependent reductions in deprivation-induced intake (24-45%). Methysergide (1 mg/kg) significantly potentiated naloxone (5 mg/kg) hypophagia after 0.5 h. Significant potentiations of hypophagia occurred following pairing the 1 mg/kg ketanserin dose with the 1 and 5 mg/kg naloxone doses at 2 and 4 h respectively, and pairing the 2.5 mg/kg ketanserin and 1 mg/kg naloxone doses at 0.5 and 2 h. Whereas the 1 mg/kg dose of ritanserin eliminated naloxone (1 mg/kg) hypophagia over a 2-h time course, ritanserin failed to exert further effects in other dose conditions. The differences between ketanserin and ritanserin in their effects upon deprivation-induced feeding and naloxone hypophagia suggest that the former's antagonistic actions upon alpha-adrenergic receptors may be responsible for its effects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1906187 TI - Predicting costs and outcomes of neonatal intensive care for very low birthweight infants. AB - A geographically determined cohort of all infants of less than 1,500 g born in 1980 and 1981 were clinically followed up to age four to determine their disabilities which were classified as mild, moderate or severe. A quality adjustment coefficient, determined by the severity of the disability, was used to calculate the number of quality adjusted lives produced. The total cost of care for these children was assessed as the sum of hospital costs to age four (which were specifically determined) and an estimate of the life-time costs of care of disabled children from information provided by the Education and Social Service departments. A very poor predictive power of birthweight with cost was obtained with the ungrouped birthweight data, whereas clinical factors explained up to 60% of the variance of the initial hospital costs for survivors and up to 30% of the variance of life-time costs and the cost of quality adjusted lives produced. Rules for the allocation of resources based on discrimination by birthweight are flawed but the application of clinical discretion is important. PMID- 1906188 TI - Baseline sister chromatid exchange in human cell lines with different levels of poly(ADP-ribose) polymerase. AB - Poly(ADP-ribose) polymerase is a chromatin enzyme which adds long chains of ADP ribose to various acceptor proteins in response to DNA strand breaks. Its primary function is unknown; however, a role in DNA repair and radiation resistance has been postulated based largely on experiments with enzyme inhibitors. Recent reports of mutant cell lines, deficient in poly(ADP-ribose) polymerase activity, have supported previous studies with inhibitors, which suggests the involvement of poly(ADP-ribose) polymerase in maintaining baseline levels of sister chromatid exchanges. Mutant cells with even slightly depressed enzyme levels show large elevation of baseline sister chromatid exchanges. Since intracellular poly(ADP ribose) polymerase levels can vary greatly between different nonmutant cell lines, we surveyed levels of baseline sister chromatid exchange in normal and tumor human cell lines and compared them with endogenous levels of poly(ADP ribose) polymerase. Despite 10-fold differences in poly(ADP-ribose) polymerase, the baseline level of sister chromatid exchanges remained relatively constant in the different cell lines (0.13 +/- 0.03 SCE/chromosome), with no indication of a protective effect for cells with high levels of the enzyme. PMID- 1906189 TI - Pancreatic enhancement after low-dose infusion of Mn-DPDP. AB - Enhancement of the pancreas was demonstrated after low-dose (10 mumol/kg) infusion of a new contrast agent for magnetic resonance (MR) imaging, manganese dipyridoxal-diphosphate (Mn-DPDP). To the authors' knowledge, this has not been described previously. The enhancement reached a maximum of 98% +/- 13% (standard deviation) during a long period (greater than 6 hours). Mn-DPDP seems to have potential as a selective contrast agent in MR imaging of the pancreas. PMID- 1906190 TI - The determination of phantom and collimator scatter components of the output of megavoltage photon beams: measurement of the collimator scatter part with a beam coaxial narrow cylindrical phantom. AB - The separation of the total scatter correction factor Sc,p in a collimator scatter component, Sc, and a phantom scatter component, Sp, has proven to be an useful concept in megavoltage photon beam dose calculations in situations which differ from the standard treatment geometry. A clinically applicable method to determine Sc is described. Measurements are carried out with an ionization chamber, placed at a depth beyond the range of contaminant electrons, in a narrow cylindrical polystyrene phantom with a diameter of 4 cm of which the axis coincides with the beam axis. Sc,p is measured in a full-scatter phantom and Sp can be derived from Sc,p and Sc. In order to obtain a reliable separation, i.e. excluding the influence of contaminant electrons, measurements of Sc,p have been carried out at depths of 5 cm for photon beams with a quality index (QI) up to and including 0.75 and a depth of 10 cm with QI larger than 0.75. These depths are in accordance with recommendations given in recent dosimetry protocols. The consistency of the method was checked by comparing calculated and measured values of Sc,p for a set of blocked fields for a range of photon beam energies from 60Co up to 25 MV showing a maximum deviation of 2%. The method can easily be implemented in existing procedures for the calculation of the number of monitor units to deliver a specified dose to a target volume. PMID- 1906191 TI - [Consensus on control of arterial hypertension in Spain. Ministry of Health and Consumption]. PMID- 1906192 TI - Lipoprotein antigens of Mycobacterium tuberculosis. AB - Detergent phase separation and metabolic labelling have been used to screen for the presence of lipoproteins amongst the antigens of Mycobacterium tuberculosis. Both techniques indicated that four antigens, with subunit molecular weights of 19, 26, 27 and 38 kilodaltons (kDa), are lipoproteins. This finding is consistent with the presence of conserved cysteine residues characteristic of other bacterial lipoproteins within the amino terminal sequences of the 38 kDa and 19 kDa proteins. It is proposed that lipoproteins are involved in the induction of humoral and cellular immune responses to mycobacteria and have a functional role in the transport of nutrients through the mycobacterial cell wall. PMID- 1906193 TI - [Influence of location for jugular venous blood sampling to cerebral circulatory index (CCI)]. AB - When cerebral circulatory index (CCI) expressed as inverse of arterial-jugular venous oxygen content difference is measured, venous sampling at the internal jugular bulb needs to be done in order to avoid mixture with extra-cerebral perfusion blood. To estimate the validity of this point, difference of values calculated with blood obtained simultaneously at the jugular superior bulb, the inferior region and the cerebral sinus were examined in monkeys. As a result, no significant differences were found to result from location of the sampling, and significant correlation between PaCO2 and CCI was recognized. These findings supported the idea that CCI reflects the cerebral blood flow due to PaCO2 changes. PMID- 1906194 TI - [A case report of a thrombosed mitral prosthesis diagnosed by 111In-oxine platelets scintigraphy]. AB - The purpose of this report was to evaluate the efficacy of 111In-oxine labeled platelets scintigraphy for detection of thrombus in the prosthetic valve. A 50 year-old man underwent re-mitral valve replacement with a Bjork-Shiley prosthesis because of malfunction of the xenograft in a previous operation. Almost one year later, this patient suffered from peripheral embolism and sight disturbance. There was no evidence of a thrombosed valve although it was suspected. Cineradiography showed the valve almost fully open, and there were no abnormal sounds when the valve closed. 111In-oxine labeled platelets scintigraphy was performed for the detection of thrombus in the mitral position. Hot areas of high quality in the scintigram were demonstrated in the mitral position. As a result, Bjork-Shiley prosthesis was replaced with a Duromedics prosthesis. A small thrombus (10mm) surrounded by fresh tiny thrombi was found in a minor orifice of the Bjork-Shiley prosthesis. PMID- 1906195 TI - Effects of central and peripheral chemoreceptor stimulation on ventilation in the marine toad, Bufo marinus. AB - The contributions of central and peripheral chemoreceptors to respiratory control in lightly anesthetized Bufo marinus, were assessed by measuring the ventilatory responses to unidirectional ventilation (UDV) of the lungs at several concentrations of CO2 or O2, during intracranial perfusion (ICP) with hypercapnic acidic (5% CO2, pH 7.2) or hypocapnic alkaline (0% CO2, pH 8.3) mock CSF solutions. Peripheral chemoreceptor stimulation alone (hypoxia or hypercapnia during ICP with hypocapnic alkaline CSF) significantly increased breathing frequency and amplitude. ICP with hypercapnic acidic CSF further stimulated ventilation, primarily by significantly increasing the number of breaths/bout of breathing and decreasing the non-ventilatory time at all levels of peripheral ventilatory drive. When peripheral and central chemoreceptor stimulation was low toads were apneic. Stimulation of either central or peripheral chemoreceptors was sufficient to reinitiate breathing. Responses to ICP were greatest when perfusion was directed to the ventral medullary surface (VMS). These results suggest that the initiation of breathing and overall levels of breathing are functions of the combined afferent input from peripheral chemoreceptors and central CO2/pH sensitive chemoreceptors, located near the VMS. Stimulation of central chemoreceptors, however, produced longer duration bouts of rhythmic breathing than did peripheral chemoreceptor stimulation. PMID- 1906196 TI - Production of 13 plasma proteins by human testicular yolk sac tumor transplanted into nude mice. AB - Thirteen human proteins were found in plasma and cystic fluid of mice bearing human testicular yolk sac tumor. Six of them, alpha-fetoprotein, prealbumin, albumin, alpha 1-antitrypsin, hemopexin and transferrin, had been previously demonstrated to be produced by yolk sac tumors. The syntheses of the remaining seven, namely apolipoprotein A1, retinol-binding protein, alpha 2HS-glycoprotein, haptoglobin, apolipoprotein B, C5 component and anti-hemophilic factor, have been demonstrated for the first time. PMID- 1906197 TI - Pharmacologic profile of sulfamino-galactosaminoglycans. PMID- 1906198 TI - Structural features and binding properties of chondroitin sulfates, dermatan sulfate, and heparan sulfate. PMID- 1906199 TI - Selenium in rheumatic diseases. AB - Selenium is involved in several important biochemical pathways relevant to rheumatic diseases. Experimental and clinical studies suggest that selenium modulates the inflammatory and immune responses. Patients suffering from inflammatory rheumatic diseases often have low selenium levels, but this finding does not correlate with disease severity. Selenium supplementation needs stricter selection criteria and better ascertainment of dose to obtain a stimulatory or inhibitory effect relevant to the disease state. Prevention of marginal selenium deficiency by moderate supplementation might enhance host defense mechanisms. PMID- 1906200 TI - Challenges to equity in health and health care: a Zimbabwean case study. AB - The current economic crisis in Africa has posed a serious challenge to policies of comprehensive and equitable health care. This paper examines the extent to which the Zimbabwe government has achieved the policy of "Equity in Health" it adopted at independence in 1980, that is provision of health care according to need. The paper identifies groups with the highest level of health needs in terms of both health status and economic factors which increase the risk of ill health. It describes a series of changes within the health sector in support of resource redistribution towards health needs, including a shift in the budget allocation towards preventive care, expansion of rural infrastructures, increased coverage of primary health care, introduction of free health services for those earning below Z$150 a month in 1980, increased manpower deployment in the public sector and the reorientation of medical training towards the health needs of the majority. The implementation of equity policies in health have however been challenged by several trends and features of the health care system, these becoming more pronounced in the economic stagnation period after 1983. These include the reduction in allocations to local authorities, increasing the pressure for fees, the static nominal level of the free health care limit despite inflation, the continued concentration of financial, higher cost manpower and other resources within urban, central and private sector health care and the lack of effective functioning of the referral system, with high cost central quaternary facilities being used as primary or secondary level care by nearby urban residents. While primary health care expansion has clearly been one of the success stories of Zimbabwe's health care post 1980, the paper notes plateauing coverage, with evidence of lack of coverage in more high risk, socio-economically marginal communities. Measures to address these continuing inequalities are discussed. Their implementation is seen to be dependent on increasing the capacity and organisation of the poor to more strongly influence policy and resource distribution in the health sector. PMID- 1906201 TI - [Infection prophylaxis in the calf-fattening operation]. PMID- 1906202 TI - [The fully-automatic analytic system Vision in horse practice in comparison with Compur M 2000 CS]. AB - We describe the utilization of the Abbott Vision system in a horse clinic and a comparison with the Compur M 2000 CS (Bayer Diagnostics and Electronics). Discrepancies were found in respect to precision and accuracy of results. Both systems showed good practicability during routine operation but different cost effectiveness. PMID- 1906203 TI - Pharmacokinetics of intratracheally administered aflatoxin B1. AB - High concentrations of the carcinogen aflatoxin B1 (AFB1) are commonly found in respirable, airborne grain dusts, and inhaled AFB1 has been shown to be a risk factor for occupational pulmonary carcinogenesis. The fate of AFB1 exposure via the respiratory tract is therefore of interest in an evaluation of potential occupational risk. The pharmacokinetic disposition of intratracheally administered AFB1 was studied in male Sprague-Dawley rats. Blood and tissues were sampled at selected intervals for 3 weeks following administration of a single dose of grain dust-adsorbed or microcrystalline [3H]AFB1 (6 micro-Ci: microgramsg/kg). The blood concentration-time profiles from both groups best approximated a two-compartment open model with first-order absorption. The first order absorption rate constant was significantly less in the animals given dust adsorbed AFB1 than in those receiving microcrystalline AFB1 (0.083 vs -0.1060 min -1, respectively), although the first-order elimination rate constants for both groups were nearly identical (0.00928 and 0.00921 hr-1, respectively). Blood concentrations of the AFB1 metabolites AFM1, AFQ1, AFL, and AFP1 showed little differences among the two groups. The tissue concentrations of aflatoxins for the microcrystalline group were significantly greater at 3 hr in all tissues examined except for the trachea and lung in which those for the dust-adsorbed group were greater. At 3 days and 3 weeks, no significant differences between exposure groups were seen in any tissue except fat, where the amount of aflatoxins was greater for the dust-adsorbed group. AFB1 binding to DNA was significantly greater in the trachea and lung of the dust-adsorbed group compared to that in the microcrystalline group at 3 hr, whereas in the liver the AFB1-DNA binding in the microcrystalline group was significantly greater during this time. Thus, particle association of AFB1 increased the respiratory tract retention of this compound at early time intervals, which might be a factor in the reputed carcinogenic action of this compound in the respiratory tract. These findings may be useful as part of a comprehensive study to evaluate the disposition of AFB1 in individuals exposed to grain dusts laden with this carcinogen. PMID- 1906204 TI - High-dose immunoglobulin therapy in four patients with onyalai. AB - Onyalai, a form of immune thrombocytopenia in Africa, has a recorded death rate of 9.8% in the acute phase due to haemorrhagic shock or central nervous system bleeding. Four patients with active bleeding and a mean platelet count of 6 x 10(9)/litre were each treated with 0.67 g/kg intravenous globulin (Sandoglobulin) daily on 3 successive days. Clinical bleeding ceased within 3 d and all patients responded with a rise in the platelet count, which peaked at 19-21 d. No side effect was recorded. Intravenous globulin therapy may reduce the morbidity of the acute phase of onyalai. PMID- 1906205 TI - Recent developments in the nutritional management of diarrhoea. 1. Nutritional strategies to prevent diarrhoea among children in developing countries. AB - This paper discusses various ways in which diarrhoea may be prevented from occurring in children living in developing countries, where it is still a major cause of morbidity and mortality. Possible strategies include promotion of breastfeeding, dietary supplementation with vitamin A, zinc and iron, the prevention of protein-energy malnutrition as far as possible, and improvement in the standard of preparation and hygiene of available weaning foods, involving in particular the wider use of fermented foods. PMID- 1906206 TI - Natural killer cell activity in visceral leishmaniasis. PMID- 1906207 TI - Recent developments in the nutritional management of diarrhoea. 2. Chronic diarrhoea and malnutrition in The Gambia: studies on intestinal permeability. AB - Chronic diarrhoea and malnutrition in Gambian children is associated with persisting damage to the mucosa of the small intestine. Intestinal permeability tests suggest that mucosal status gradually deteriorates with age throughout the first year of life in tandem with increasingly severe growth faltering. The ability of the dual sugar permeability test to assess intestinal mucosal status frequently in a non-invasive way makes the technique a valuable tool for future studies into the aetiology of this syndrome. PMID- 1906208 TI - Pilot study of the potential use of leucocyte adherence to Schistosoma haematobium eggs as an indication of immunity to reinfection. PMID- 1906209 TI - Integrated maps of the Drosophila genome: progress and prospects. AB - A physical map of the Drosophila melanogaster genome is being assembled, consisting of ordered overlapping cosmid clones. The map is constructed in steps, separately for each chromosomal division. Gaps in this map are to be bridged with yeast artificial chromosome clones. Hybridization to previously cloned genes and extensive use of in situ hybridization to polytene chromosomes ensure that the cosmid map is firmly anchored to the wealth of available genetic and cytogenetic information. The intention is to make the physical map widely available as part of an overall, integrated genetic resource for the Drosophila research community. PMID- 1906210 TI - Compartmentalized gene expression during sporulation in Bacillus subtilis. AB - Two important features of endospore development in Bacillus subtilis--the compartmentalization of mother cell gene expression and the coordination of mother cell gene expression with forespore development--are governed by the highly regulated expression of the sigK gene, which encodes the mother cell specific RNA polymerase sigma factor sigma K. Compartmentalized expression of sigK is associated both with a chromosomal DNA rearrangement and with the restriction of sigK transcription to the mother cell. A third mode of sigK regulation, which occurs at the level of activation of the sigK gene product by proteolytic processing, serves to couple gene expression between the mother cell and forespore compartments of the developing sporangium. PMID- 1906211 TI - Spatial regulation of photosynthetic development in C4 plants. AB - Leaf development in C4 plants requires the morphological and functional differentiation of two photosynthetic cell types (bundle sheath and mesophyll). Photosynthetic reactions are split between bundle sheath and mesophyll cells, with each cell type accumulating a specific complement of photosynthetic enzymes. Current evidence suggests that in order to activate this cell-specific expression of photosynthetic genes, bundle sheath and mesophyll cells must interpret positional information distributed locally around each vein. PMID- 1906212 TI - Production of monoclonal antibody in plants. PMID- 1906213 TI - [Aztreonam, a new approach in the therapy of gonorrhea]. AB - The isolated gonococcal strains cultured from 99 patients (64 men and 35 women) with uncomplicated genital gonorrhoea were tested with regard to their susceptibility to aztreonam. No resistant strain was found. The bacteriological evaluation of 50 of these strains showed a minimum inhibitory concentration (MIC) of 0.0075 to 3.906 mcg/ml. Four of the tested strains were penicillinase producing strains of N. gonorrhoeae. 95 patients (95.9%) were cured after administration of a single dose of 1 g aztreonam by intramuscular injection. It was not possible to exclude reinfection of the 4 remaining patients. No side effects were reported. PMID- 1906214 TI - [Immunoturbidimetric determination of C-3 components of complement systems using nonlinear calibration]. AB - A method for the immunoturbidimetric analysis of the C-3-component in the complement system was elaborated by means of the antiserum Q-SwAHu/C3 USOL (SEVAG) Praha. A diluted human control serum USOL (SEVAG) Praha with declared values of plasma proteins was applied as a standard solution. The relation between concentration and absorption in an eight step calibration series is well described by a parabola of the 2nd degree. The precision in series and the accuracy of the method are mentioned. The proposed technique is in a relatively good correlation with the radial immunodiffusion according to MANCINI. PMID- 1906215 TI - [Hydrophobicity and microbial production. 1. Selection of oleophilic microorganisms and qualitative characterization by several ecologically and technologically relevant activities]. AB - From samples of different origin microorganisms were selected using the property of oleophily. All oleophilic isolates (30 strains are characterized in more detail) proved to be Gram-positive, nonsporogenic bacteria, obviously belonging to the group of coryneforms. They are growing on a broad spectrum of substrates, 11 strains are facultatively methylotrophic. They are utilizing methanol as well as n-alkanes and glucose without any supplines. 6 strains are able to degrade and decolorize triphenylmethane dyes, for example crystal violet and malachite green. Because of the degradative capacities, combined with the hydrophobic properties of the cell surface, the group of the oleophilic bacteria seems to be very promising in relation to the development of environmental technologies and ecological investigations. PMID- 1906216 TI - Characteristics of lactobacilli isolated from the chicken intestine. AB - Nine strains of lactobacilli isolated from different parts of the intestinal tract of chicken were studied to determine their taxonomy and cultural characteristics. The experimental scheme included physiological and biochemical tests, morphological observations and determination of fermentation products from glucose. All isolates were heterofermentative organisms assigned to the Lactobacillus fermentum species. The relevance of intestinal lactobacilli to the nutrition of chickens was discussed. PMID- 1906217 TI - Inhibition of growth hormone secretion by activin A in human growth hormone secreting tumour cells. AB - Effect of activin A on growth hormone secretion was studied in primary culture of 8 human GH-secreting adenomas, which were responsive to TRH in vivo. When studied in vitro, basal GH secretion was reduced in all cases when cells were pre incubated for 48 h with activin A at a concentration of 5 X 10(-9) mol/l or greater. Pretreatment of GH-secreting cells with 1 X 10(-9) mol/l activin A did not affect either basal secretion or cellular content of GH. These tumour cells also responded to TRH in vitro and the GH response to TRH was completely blocked in cells pretreated with activin A. Activin A slightly reduced the increase in cytoplasmic free calcium concentration induced by TRH. Furthermore, pretreatment of the cells with activin A attenuated GH secretion induced by A23187 or 12-O tetradecanoyl phorbol-4-acetate, agents which bypass receptor-mediated generation of second messengers. These results indicate that activin A inhibits GH secretion by directly acting on human GH-secreting cells and that activin A inhibits the action of TRH by acting on multiple steps in the messenger system. PMID- 1906218 TI - Laser labyrinthectomy in humans. AB - This paper describes the feasibility of labyrinthectomy of only the vestibular part using argon laser in humans. In animal experiments, the utricular and saccular maculae were completely destroyed using argon laser with the otoprobe of the HGM system via the oval window, following stapedectomy. The human utricular and saccular maculae can be approached in a similar manner. Several approaches to the nerves and ampullae of the anterior and lateral semicircular canals are discussed. The most appropriate method to abolish the function of the ampullae is to sever the ampullary nerves. This can be done through the widened oval window with the argon laser otoprobe. After laser application, the oval window is covered by a piece of perichondrium. A stapes prosthesis is placed on the long process of the incus. Laser singular neurectomy may be used to sever the nerve to the posterior ampulla. PMID- 1906219 TI - Gas diffusion in the middle ear. AB - The ex vacuo theory, claiming that in cases of middle ear underaeration air enters the middle ear through the Eustachian tube in diminished amounts while oxygen continues to leave it into the blood by diffusion as in normal condition, does not provide a complete explanation for the aeration problems encountered in middle ear pathology. This study shows that when atelectatic ears are politzerized (hyperinflated) with different gases, these gases disappear with a speed that correspond to the diffusion coefficient of the different gases. This finding together with the fact that the composition of middle ear gases is very similar to that found in the venous circulation suggests that it is a diffusional process of several gases from the middle ear into the blood and in the opposite direction that mainly determines the middle ear pressure. PMID- 1906220 TI - Compensatory mechanisms induced by high oropharyngeal airway resistance in rats. AB - Acid base balance changes were observed during 72 h following bilateral nasal obstruction in rats. Mouth breathing caused acute respiratory acidosis and marked aerophagia, leading to spontaneous death of the experimental animal 80 to 90 h postoperatively. Stenotic oropharyngeal airway, due to palatal-epiglottic approximation, is supposed to be responsible for respiratory insufficiency in the nose obstructed rats. The compensatory changes in respiratory mechanics caused by high oropharyngeal airway resistance, together with some possible reflex changes, may have caused either air swallowing or aspiration. As changes in acid base balance parameters did not show breakdown of the compensatory mechanisms during the first 72 h postoperatively, it is supposed that the increased air volume in stomach and guts, causing elevation of the diaphragm and paralytic ileus, contributed to the experimental animals' death. PMID- 1906221 TI - The role of DNA synthesis in the responses of fetal rat calvariae to cortisol. AB - To determine the extent to which the effects of cortisol on collagen synthesis in 21 day fetal rat calvariae are linked to its effects on cell replication, calvariae were cultured for 24-72 h with 0.1 and 1 microM cortisol in the presence or absence of 1 mM hydroxyurea (HU) or 30 microM aphidicolin (APC), inhibitors of DNA synthesis. The incorporation of [3H]proline into collagenase digestible protein (CDP) and [3H]thymidine into DNA were measured during the last 2 h of culture. At 24 h HU and APC decreased thymidine incorporation by greater than 90%, and this remained low for the duration of culture. In contrast, cortisol reduced thymidine incorporation by only 44% at 72 h. Although cortisol caused a 24 h stimulatory effect and a 48 and 72 h inhibitory effect on CDP labeling and the percentage of collagen being synthesized (PCS), HU, and APC had no effect on basal CDP labeling or PCS over the 72 h culture period. Cortisol caused parallel alterations in the steady-state levels of alpha-1(I) procollagen mRNA, suggesting that its effects occur at the pretranslational level. At 24 h HU and APC did not prevent the stimulatory effect of cortisol on CDP labeling and PCS. At 48 h the inhibitory effects of cortisol on CDP labeling and PCS were observed in the presence of APC but not in the presence of HU. At 72 h the inhibitory effects of cortisol on CDP labeling and PCS were still observed in the presence of HU and APC.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1906222 TI - Two classes of azo dye reductase activity associated with rat liver microsomal cytochrome P-450. PMID- 1906223 TI - Expression of a cDNA encoding rat liver DT-diaphorase in Escherichia coli. PMID- 1906224 TI - The role of hepatic metabolites of benzene in bone marrow peroxidase-mediated myelo- and genotoxicity. PMID- 1906225 TI - Lung vascular injury from monocrotaline pyrrole, a putative hepatic metabolite. AB - The pyrrolizidine alkaloid, monocrotaline (MCT), is a plant toxin that causes injury to the vasculature of the lungs and pulmonary hypertension in animals. To produce lung injury, MCT is bioactivated in the liver by cytochrome P450 monooxygenases to pyrrolic metabolites which travel via the circulation to the lungs, where they cause injury by unknown mechanisms. One putative metabolite of MCT is monocrotaline pyrrole (dehydromonocrotaline, MCTP), a moderately reactive, bifunctional alkylating agent. A single, iv injection of chemically synthesized MCTP into rats causes delayed and progressive lung vascular injury and pulmonary hypertension similar to that caused by MCT itself. Since pulmonary vascular endothelium is likely an important target of MCTP in vivo, the effects of MCTP on cultured endothelium were studied. A single application of MCTP to confluent monolayers of cultured endothelium from bovine pulmonary artery results in release of lactate dehydrogenase, some cell detachment from the growth surface and markedly altered morphology of remaining viable cells. These effects are dose dependent and, as in vivo, are delayed in onset (1-2 days) and progressive. In endothelial cells of porcine origin, these particular responses to MCTP are also apparent but much less pronounced. Inhibition of proliferation of cells plated at low density occurred in both cell types at nominal MCTP concentrations (0.5 micrograms/ml) that were not overtly cytotoxic. These results indicate that MCTP causes a direct, dose-dependent injury to pulmonary vascular endothelium in culture that is delayed and progressive and suggest a mechanism by which MCT may act in vivo to cause lung injury and pulmonary hypertension. PMID- 1906226 TI - Bisfuranoid mycotoxins: their genotoxicity and carcinogenicity. AB - Based on the mode of action of AFB1 and the activities of its biologically active intermediates, one may conclude that: 1. The mode of toxic action of the bisfuranoid mycotoxin is through epoxidation of the vinyl ether double bond of their dihydrobisfuran functionality. 2. The DNA and plasma albumin adducts formed in vivo may be useful in the molecular dosimetry of these environmental carcinogens. 3. There appears to be a linear correlation between the steady state levels of AFB1-FAPy-DNA adducts and the carcinogenicity of AFB1. Elucidation of the molecular basis of this correlation may shed light on the mechanism of AFB1 induced carcinogenesis. 4. Consistent appearance of AFB1-DNA adducts in the livers of liver cancer patients tested is supportive of the IARC conclusion that AFB1 is a human carcinogen involved in human primary liver cancer. PMID- 1906227 TI - Electrophilic sulfuric acid ester metabolites of hydroxy-methyl aromatic hydrocarbons as precursors of hepatic benzylic DNA adducts in vivo. PMID- 1906228 TI - Sulfur conjugates as putative pneumotoxic metabolites of the pyrrolizidine alkaloid, monocrotaline. PMID- 1906229 TI - Trapping of reactive intermediates by incorporation of 14C-sodium cyanide during microsomal oxidation. PMID- 1906230 TI - Physiological and toxicological roles of hydroperoxides. PMID- 1906231 TI - Comparison of 8-hydroxydeoxyguanosine and 5-hydroxymethyluracil as products of oxidative DNA damage. PMID- 1906232 TI - Biochemical effects and toxicity of mitoxantrone in cultured heart cells. PMID- 1906233 TI - Studies on biochemical determinants of quinone-induced toxicity in primary murine bone marrow stromal cells. PMID- 1906234 TI - Infection characteristics of Schistosoma japonicum in mice and relevance to the assessment of schistosome vaccines. PMID- 1906235 TI - Analgetic activity of SK&F 105809, a dual inhibitor of arachidonic acid metabolism. AB - The analgetic activity of inhibitors of 5-lipoxygenase (5-LO) and cyclooxygenase (CO) was investigated using rat Randall-Selitto (RS) hyperalgesia and mouse phenylbenzoquinone (PBQ)-induced abdominal constriction assays. Using the RS assay, the CO inhibitors indomethacin, naproxen, and ibuprofen all effectively reduced hyperalgesia; whereas, the inhibitors of leukotriene production, MK886 and phenidone were inactive. SK&F 105809, a dual inhibitor of 5-LO/CO, significantly reduced hyperalgesia. In the PBQ assay, CO inhibitors were active, SK&F 105809 was nearly as potent as naproxen, and MK886 and phenidone were found to be active. Thus, improved analgetic activity appeared to result from inhibition of 5-LO and CO; whereas, in the RS assay, only CO inhibitors and SK&F 105809 were clearly effective. These results suggest that dual inhibitors, and in particular, SK&F 105809 may be more efficient analgesic agents than selective CO inhibitors in clinical situations in which 5-LO products play a significant role. PMID- 1906236 TI - A new antiinflammatory agent (EGIS-5645) without gastrointestinal side-effect. AB - The compound EGIS-5645 is a potent antipyretic agent possessing analgesic and antiinflammatory properties. The drug is active in antiinflammatory models such as carrageenin oedema and adjuvant arthritis. EGIS-5645 shows practically no gastro-ulcerogenic effect. The molecule does not inhibit either prostaglandin biosynthesis or soybean lipoxygenase enzyme activity. PMID- 1906237 TI - Influence of an intravenous dose of aurothiomalate on the status of low-molecular mass endogenous metabolites in blood plasma: a proton nuclear magnetic resonance (NMR) study. AB - The effect of aurothiomalate on the status of a wide range of low-molecular-mass endogenous metabolites in blood plasma obtained from animals treated with an intravenous dose of this second-line agent (150 mg/kg) has been assessed by high field proton Hahn spin-echo NMR spectroscopy. As well as modulating the effective concentrations of NMR-detectable biomolecules, aurothiomalate induces a time dependent decrease in plasma levels of triacylglycerols with a corresponding elevation in the concentration of the ketone body 3-D-hydroxybutyrate, indicating an increased utilisation of fats for energy in rats treated with this 1:1 gold(I) thiolate complex. These observations may reflect the toxic side-effects that are associated with aurothiomalate treatment. PMID- 1906238 TI - Influence of disodium aurothiomalate on the activities of xanthine dehydrogenase and xanthine oxidase in endothelial cells. AB - The effect of aurothiomalate in modulating the conversion of xanthine dehydrogenase to its superoxide producing oxidase form in rat and human liver cytosolic preparations has been investigated. Low concentrations (10(-8)-10(-5) mol.dm-3) of this second-line agent were found to inhibit the conversion of the dehydrogenase to its corresponding oxidase form. High concentrations (10(-4) mol.dm-3), however, accelerated this conversion. It is possible that the influence of aurothiomalate on the relative proportions of xanthine dehydrogenase and xanthine oxidase is a reflection of the gold(I) blockage of critical thiol(ate) or sulphido ligands present in this enzymatic system. These effects may form the basis of aurothiomalate's anti-proliferative action on endothelial cells. PMID- 1906239 TI - [Clinical phase III study on TAP-144-SR, an LH-RH agonist depot formulation, in patients with prostatic cancer]. AB - A randomized controlled phase III clinical trial comparing TAP-144-SR (TAP) and diethylstilbestrol diphosphate was conducted for patients with prostatic cancer. Patients with Stage B, C, or D disease, who were previously untreated, were enrolled. TAP-144-SR 3.75 mg was administered subcutaneously at 4-week intervals for 12 weeks (a total of 3 injections) in the TAP-144-SR group, while 100 mg of diethylstilbestrol diphosphate was administered orally three times a day (before meals) for 12 weeks in the control group. A total of 141 patients were enrolled using a centralized telephone registration system. Four of these patients were ineligible, and there were 3 drop-outs who never received drugs because they withdrew their consents to participate in the trial. These 7 were excluded from the evaluation, and as a result, 134 patients (66 in the TAP group and 68 in the control group) were evaluable in safety and efficacy. Between the two groups, there were no significant differences in patient characteristics, except the age distribution. Clinical response rates (CR+PR) in evaluable patients according to the criteria of Japanese Prostatic Cancer Study Group were 54.5% in the TAP group and 47.1% in the control group. In addition, the rates according to the criteria for Evaluating the Direct Response to Chemotherapy in Solid Carcinomas and NPCP criteria were 7.6% in the TAP group and 8.8% in the control group and 18.2% in the TAP group and 20.6% in the control group, respectively. Using any of the three criteria, there were no significant differences in response rate between the two groups. The incidence of side effects was 64.1% in the TAP group and 95.4% in the control group; the incidence being significantly higher in the control group (p less than 0.001; chi 2-test). Therefore, the overall safety was significantly greater in the TAP group than in the control group (p less than 0.001; chi 2-test). On the basis of the efficacy and safety the clinical usefulness rate of TAP-144-SR was significantly higher than that of diethylstilbestrol diphosphate (p = 0.038; U-test). In conclusion, TAP-144-SR was confirmed to be more useful than diethylstilbestrol diphosphate as a standard drug for hormonal therapy of prostatic cancer. PMID- 1906240 TI - Catalase-negative listeria monocytogenes causing meningitis in an adult. Clinical and laboratory features. AB - A 63-year-old previously healthy woman presented with acute meningitis. Cultures of the cerebrospinal fluid yielded a serotype 1/2a isolate of Listeria monocytogenes that was biochemically typical in all respects, other than the reproducible lack of catalase production. During therapy, the patient developed oculomotor dysfunction that was attributed to an abscess in the internal capsule. This case report documents the existence of catalase-negative L. monocytogenes indicating that catalase production should not be a strict criterion for identification of Listeria. Furthermore, this clinical experience extends in vitro and experimental animal studies indicating that catalase production is not a necessary virulence factor for invasion by Listeria. PMID- 1906241 TI - EDTA-dependent leukoagglutination. PMID- 1906242 TI - Splenectomy for a case with Waldenstrom macroglobulinemia with giant splenomegaly. PMID- 1906243 TI - Medical imaging in cochlear implant candidates. AB - A retrospective study of preoperative radiographic surveys obtained in 85 cochlear implant patients was performed. A total of 90 cochlear implant patients were seen at our institution during the last 10 years. In three, the implant was placed at another institution. In two otosclerosis patients, no preimplant radiographic examination was obtained. Meningitis was the cause of deafness in 45 of 90 patients (50 percent); 28 of 40 pediatric age group patients (70 percent), and in 17 of 50 adult patients (34 percent). Thirty-three of 45 postmeningitis patients (73 percent) showed characteristic radiographic signs of sclerosing labyrinthitis or labyrinthitis ossificans. These signs were present in only one other patient who was deaf with unknown cause. Deformity of the inner ear sufficient to explain congenital deafness was noted in three cases; one Mondini deformity and two obliterated base of the cochlea (modiolus). Three otosclerosis patients who had preimplant radiographs, and one congenital syphilis patient showed classic radiographic signs of their respective diseases. Obliteration or stenosis of the round and/or the oval windows were observed in 26 cases drawn from all major etiologic groups. State-of-the-art high resolution, thin-section CT can demonstrate subtle changes that may be the only clue to the cause of deafness. MRI promises to be a useful technique to follow meningitis patients with membraneous labyrinth changes progressing to sclerosing labyrinthitis. PMID- 1906244 TI - Ganglion cell populations in labyrinthitis ossificans. AB - Ossification of the perilymphatic spaces of the inner ear is frequently found in patients with profound deafness who may be candidates for cochlear implantation. The ossification may be a hindrance in electrode insertion and has previously been considered a relative contraindication to implantation. The quantity of peripheral auditory elements remaining in a series of patients with labyrinthitis ossificans has not been reviewed. We performed a histopathologic study of 16 temporal bones with partial cochlear ossification of multiple etiologies. The organ of Corti and spiral ganglion were graphically reconstructed. The degree of obstruction was estimated for each millimeter of the scala tympani and scala vestibuli. A quantitative evaluation of the sensorineural elements of the inner ear (spiral ganglion cells, inner and outer hair cells, and peripheral auditory axons) was performed. The results were compared with 16 control patients with normal hearing and no evidence of cochlear ossification. Our results show that the greatest amount of damage is found in the organ of Corti with preservation of a significant number of spiral ganglion cells in most cases. A wide range of ganglion cells (6,310 to 28,196) was found in patients with labyrinthitis ossificans with the mean number of ganglion cells being 17,152. A profound sensorineural hearing loss was noted in all patients except one. Meningogenic labyrinthitis and otosclerosis were associated with the greatest loss of ganglion cells. The location of ossification could be correlated with the region showing loss of the organ of Corti. In the majority of patients, the location of ossification and fibrosis could not be correlated with the region of the spiral ganglion showing loss of ganglion cells. The implications of these findings for cochlear implantation is discussed. PMID- 1906245 TI - Introduction: use of tunnelled right atrial catheters in children with malignant diseases. PMID- 1906246 TI - Evaluation of a home intravenous antibiotic program in pediatric oncology. AB - We conducted a pilot program of home intravenous antibiotic therapy for the management of febrile neutropenic episodes in a population of children with cancer. During a 6-month period, 13 children/families participated in the successful treatment of 22 episodes of infection. A cost analysis of the program indicates that home therapy is considerably cheaper than in-hospital treatment. Although the program represents an incremental cost to the hospital, it does provide for more efficient health care delivery. Feedback from parents who participated was highly favorable. We believe that home intravenous antibiotic therapy is a safe and efficacious alternative to hospital management of children with malignant diseases admitted with fever and neutropenia. PMID- 1906247 TI - Cardiopulmonary function during long-term central venous catheterization. AB - A prospective study was performed in an ambulatory group of infants, children, and young adults with neoplastic disorders to determine the prevalence of significant cardiopulmonary complications during long-term central venous catheterization. A cohort of 20 consecutive patients who had central venous catheters in situ for a mean of 13.5 months underwent pulmonary function testing, chest radiography, ventilation perfusion lung scintigraphy, electrocardiography, and echocardiography. No significant complications were seen. Specifically, there was no evidence of localized thrombus formation or pulmonary emboli, and no indirect evidence of pulmonary hypertension. In addition, we reviewed retrospectively the autopsy reports of 15 patients who died with central venous catheters in place. Three of these patients had superficial endocardial reactions. One patient had a right atrial mural thrombus related to the catheter, but two other patients were noted to have left atrial mural thrombi. This study demonstrates that central venous catheters can be used safely on a long-term basis in ambulatory patients requiring frequent venous access for treatment of their neoplastic disorders. PMID- 1906248 TI - Is propofol cost-effective for day-surgery patients? AB - To attempt to justify the expense of using propofol for day-surgery, we have compared propofol with methohexitone for induction of anaesthesia for elective minor gynaecological procedures. Seventy healthy patients were randomised to receive either induction agent and postoperatively they were compared for recovery times, side-effects and patient appraisal the following day. The results showed that propofol was superior to methohexitone for most parameters, with small but statistically significant differences in response time, ambulation time, vomiting and drowsiness during recovery. There were minor differences in patient appraisal the next day. However, it is doubtful whether the advantages of propofol are sufficiently substantial to justify the expense of its routine use in preference to methohexitone and its place is a matter for individual judgement. PMID- 1906249 TI - Use of end-tidal CO2 sampling connector to administer bronchodilators into the anaesthetic circuit. PMID- 1906250 TI - Expression of transforming growth factor-beta, tumor necrosis factor-alpha, and leukemia inhibitory factor mRNAs in rodent and human hematopoietic cells. PMID- 1906251 TI - Synergism between interferon-gamma and colony-stimulating factor in the stimulation of clonogenic cell growth in acute myeloblastic leukemia. PMID- 1906252 TI - Characterization of a novel erythropoiesis-inhibiting human protein. AB - We have isolated an erythropoiesis-inhibiting protein, DIP (differentiation inhibiting protein), from the blood of a 60-year-old woman suffering from pure red cell aplasia. This protein inhibits the growth and differentiation of normal human and murine BFU-E, but not CFU-E, cells as well as dimethyl sulfoxide induced hemoglobin synthesis by Friend murine erythroleukemia cells. It appears that DIP primarily affects differentiation rather than proliferation, because it does not inhibit the proliferation of untreated Friend erythroleukemia cells. DIP seems to function like a recently described 45-kDa autocrine differentiation inhibiting protein factor (ADIF) which is secreted by tsAEV-transformed chicken erythroleukemia cells. Both proteins selectively block the differentiation of normal human and murine BFU-E cells as well as the differentiation (but not the proliferation) of Friend murine erythroleukemia cells. However, the human DIP is not an autocrine product of the patient's bone marrow cells, nor does it affect chicken erythroid cells. PMID- 1906253 TI - Negative regulation of cytokines. Inhibition of the production of interleukin-1 and tumor necrosis factor. PMID- 1906254 TI - Inhibition of major histocompatibility complex class I antigen shedding up regulates the surface expression of class I antigens on the lymphocyte cell surface. AB - Interferon-gamma induces the expression of major histocompatibility complex class I and class II gene products. Moreover, the density of MHC antigens present on the lymphocyte surface is regulated by exfoliation of the plasma membrane. To probe the cellular mechanisms involved in IFN-gamma-induced alteration of MHC antigen expression, we measured the effects of IFN-gamma on the rate of MHC antigen shedding and the biosynthesis of H-2Dd. Balb/c splenic lymphocytes were surface-iodinated with 125I and incubated in the presence and absence of up to 1000 U/ml IFN-gamma, or they were metabolically labeled with [35S]methionine with or without 500 U/ml IFN-gamma. Radioiodinated or 35S-labeled H-2Dd was quantified by immunoprecipitation of H-2Dd from detergent lysates of radiolabeled cells that were incubated with the appropriate antibody for 4-20 h at 37 degrees C. Monoclonal antibody 34-5-8 was employed as a specific probe for H-2Dd. Loss of radioiodinated H-2Dd from the cell surface was diminished by 75-90% at 12 h in tests of lymphocytes continuously cultured with IFN-gamma (compared to control, p less than 0.05). In contrast, the biosynthetic rate was unaffected during the initial 10 h of incubation. The net result of these changes was the early appearance of an increase in H-2Dd on the cell surface. This result was in accordance with data obtained by phenotyping the untreated and treated cells using double-antibody staining methods and fluorescence-activated cell sorter analysis. Our results suggest that IFN-gamma induces MHC expression by initially retarding the exfoliation of MHC antigens from the lymphocyte surface. Delayed effects on MHC expression may be, on the other hand, mediated by increased antigen biosynthesis. PMID- 1906255 TI - Down-regulation of bone marrow stem cell formation by T cell subsets. Effect of CD8+ cells on colony formation in peripheral blood and bone marrow. PMID- 1906256 TI - Leukemia inhibitory factor: does the cap fit? PMID- 1906257 TI - [The treatment of ketoacidosis in children and adolescents with diabetes (simultaneous major ketosis and severe hypoglycemia)]. AB - Ketoacidosis in pediatric diabetes mellitus remains an active problem. Although the authors have recorded no deaths among their own patients, fatal cases still occur in France and other countries, usually as a result of inappropriate therapy, sometimes based on mistaken immediate pathophysiologic interpretations of laboratory test results. A very simple protocol based on the author's extensive experience is proposed. Rehydration solutions (optimal sodium bicarbonate, isotonic saline for the first two hours, then 10% glucose solution with electrolytes infused at a fixed rate of 3 l/m2 body surface area) are given at the same time as insulin (22 units per liter in each infusion flask). This protocol is remarkably effective and gives rise to no complications. In extreme conditions, reagent strip assays of blood glucose levels and evaluation of acidosis by respiratory rate measurements would suffice to ensure appropriate monitoring. A simple method for treating hypoglycemia is also described. PMID- 1906258 TI - [Cefaclor versus penicillin V in staphylococcal infections in children]. AB - Although rheumatic fever virtually no longer occurs in France, pharyngitis due to group A beta-hemolytic streptococci (ABHS) remains a common pediatric problem. American studies have underscored the high rate of bacteriologic treatment failures and recurrences of ABHS pharyngitis. Furthermore, several comparative studies have demonstrated that cephalosporins provide better results on these two parameters. This prospective randomized study compared the effectiveness of penicillin V (50,000 to 100,000 IU/kg/day in three divided doses) and Cefaclor (20 to 40 mg/kg/day in three divided doses), each given for ten consecutive days. From September 1989 through October 1990, 117 children (mean age 5.7 years) were entered into the study. All study subjects were seen as outpatients and found to have ABHS pharyngitis on the basis of a rapid screening test and confirmatory bacteriologic studies. Cefaclor was given to 56 patients and penicillin V to 61. Reevaluation with a repeat bacteriologic study was performed in all patients at the end of the treatment period, or earlier in the event of new clinical manifestations, and towards D40. Among patients given penicillin V, bacteriologic failure rate at completion of therapy was 19.6%, clinical failure rate on D10 was 8%, and recurrence rate on D40 was 16.5%. Cefaclor exhibited greater bacteriologic and clinical effectiveness, with 3.4% bacteriologic failures on D10 (p less than 0.01), 1.7% clinical failures on D10, 8.9% clinical recurrences between D10 and D40, and an overall 10.6% rate of failure or recurrence (p = 0.05). PMID- 1906259 TI - Pharmacokinetics of 2',3'-dideoxyinosine (BMY-40900), a new anti-human immunodeficiency virus agent, after administration of single intravenous doses to beagle dogs. AB - The pharmacokinetics of 2',3'-dideoxyinosine (ddI) were investigated in four adult male beagle dogs that received 15-min infusions of 20-, 50-, and 100-mg/kg doses in a randomized crossover study design. Plasma and urine samples were collected for 10 and 24 h, respectively, and assayed for ddI by high-performance liquid chromatographic methods. The mean maximum concentrations of drug in plasma at the end of 15-min infusions for the 20-, 50-, and 100-mg/kg doses were 33.3, 90.0, and 202 micrograms/ml, respectively. Area under the concentration-time curve data deviated significantly from linearity. The mean total clearance for the low dose (250 ml/min) was significantly greater than that for the high dose (190 ml/min). Renal clearance, which averaged between 98 and 116 ml/min, was dose independent. Renal clearance implied that nonrenal clearance decreased at the high dose (92 ml/min) when compared with that of the low dose (134 ml/min). The average urinary recovery of ddI for the high dose (51.2% of dose) was significantly greater than that for the low dose (45.8%). The volume of distribution at steady state averaged between 7.6 and 10.5 liters and decreased with increasing dose; however, it was not statistically significant. The mean half-life and mean residence time were invariant with respect to dose and averaged between 0.94 and 1.07 h and 0.61 and 0.71 h, respectively. In this dose range, ddI pharmacokinetics are dose dependent. PMID- 1906260 TI - Characterization of a gyrB mutation responsible for low-level nalidixic acid resistance in Neisseria gonorrhoeae. AB - Nalidixic acid-resistant derivatives of Neisseria gonorrhoeae WR302 were identified and categorized into two classes on the basis of their susceptibilities to this antimicrobial agent. The MIC of nalidixic acid for the derivative strain MUG116 was fourfold greater than that for its isogenic parental strain WR302 (2 versus 0.5 micrograms/ml, respectively). MUG324 was significantly more resistant to nalidixic acid (greater than 64 micrograms/ml). The MICs of other antimicrobial agents known to interact with either the gyrA or gyrB gene products were determined. Although the nalidixic acid MIC for MUG116 increased, no significant increases in the MICs of other agents that interact with the gyrA gene product were seen. The MICs of all agents that interact with the gyrA gene product were significantly increased for MUG324. The gene that imparts low-level nalidixic acid resistance was cloned from strain MUG116. The DNA sequence of this gene was determined, and by comparing the deduced amino acid sequence with sequences of proteins in data bases, this protein was found to be approximately 70% homologous with the gyrB gene product of Escherichia coli. PMID- 1906261 TI - In vitro and in vivo evaluation of Ro 09-1428, a new parenteral cephalosporin with high antipseudomonal activity. AB - Ro 09-1428, a new parenteral cephalosporin with a catechol moiety attached at position 7 of the cephalosporin ring, showed high in vitro activity against Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Proteus vulgaris, and Streptococcus pyogenes, with MICs for 90% of strains tested (MIC90s) of less than or equal to 0.39 micrograms/ml. Morganella morganii, Providencia rettgeri, Citrobacter freundii, Haemophilus influenzae, Staphylococcus aureus, and Streptococcus pneumoniae were inhibited with MIC90s of less than or equal to 3.13 micrograms/ml. Serratia marcescens was less susceptible to Ro 09-1428, with a MIC90 of 25 micrograms/ml. The most distinctive feature of Ro 09-1428 was its potent activity against Pseudomonas aeruginosa and Acinetobacter calcoaceticus, with MIC90s of 0.39 and 6.25 micrograms/ml, respectively. Most of the ceftazidime resistant strains of P. aeruginosa, E. cloacae, and C. freundii were inhibited by Ro 09-1428, while those of S. marcescens were resistant at a concentration of 12.5 micrograms/ml. Ro 09-1428 was more active than ceftazidime against staphylococci. PBP 3 was the most sensitive target in E. coli and P. aeruginosa. The response to ferric iron in growth medium suggests that Ro 09-1428 may be taken up by transport mechanisms similar to those of other catechol cephalosporins. In accordance with its in vitro activity, Ro 09-1428 activity was equal to or greater than ceftazidime activity in efficacy against experimental septicemias in mice. The results indicate that Ro 09-1428 is a broad-spectrum cephalosporin with advantages over ceftazidime in its activity against P. aeruginosa, staphylococci, and ceftazidime-resistant strains of C. freundii and E. cloacae. PMID- 1906262 TI - Hyperoxia prolongs the aminoglycoside-induced postantibiotic effect in Pseudomonas aeruginosa. AB - The objective of this study was to determine whether hyperoxia enhances aminoglycoside activity against Pseudomonas aeruginosa. The existence of tobramycin-oxygen synergy was determined by using the in vitro postantibiotic effect (PAE). P. aeruginosa strains were incubated for 1 h in medium containing tobramycin at four times the MIC in the following gas mixtures: normoxia (21% O2), hyperoxia (100% O2, 101.3 kPa), or hyperbaric oxygen (100% O2, 274.5 kPa). Tobramycin was removed after 1 h and bacteria were incubated under normoxic conditions; growth rates were measured for 5 h. Exposure of three P. aeruginosa strains to hyperoxia prolonged the PAE of tobramycin approximately twofold compared with the PAE after exposure to normoxia (P less than 0.05). Exposure of P. aeruginosa ATCC 27853 to tobramycin and hyperbaric oxygen prolonged the time required for bacteria to increase 1 log10 CFU/ml compared with the time after exposure for this increase to occur in tobramycin-treated, normoxic or hyperoxic groups (P less than 0.02). Pulse-chase labeling of bacteria with L [35S]methionine, immediately after removal of tobramycin, showed that protein synthesis rates were decreased compared with those in controls (P = 0.0001). Moreover, in tobramycin-treated groups, hyperoxia and hyperbaric oxygen induced 2 and 16-fold decreases, respectively, in protein synthesis rates compared with normoxia; these results did not achieve statistical significance. In the absence of tobramycin, hyperoxia increased bacterial growth (134%; P less than 0.01) and protein synthesis (24%; not significant) compared with normoxia. Hyperbaric oxygen, however, delayed the growth recovery of bacteria (P less than 0.05). We conclude that hyperoxia enhances the bacteriostatic effects of tobramycin in a synergistic manner.+ PMID- 1906263 TI - Imipenem resistance in pseudomonas aeruginosa PAO: mapping of the OprD2 gene. AB - Carbapenem antibiotics have been shown to penetrate the outer membrane of Pseudomonas aeruginosa through a unique porin protein, OprD2. We mapped the OprD2 gene by conjugation using plasmid FP2 and by transduction using phage F116L. This gene maps between 71 and 75 min on the PAO1 chromosome. PMID- 1906264 TI - Comparative activity of cefepime, alone and in combination, against clinical isolates of Pseudomonas aeruginosa and Pseudomonas cepacia from cystic fibrosis patients. AB - The comparative in vitro activity and synergy of cefepime were evaluated with clinical isolates of Pseudomonas aeruginosa and Pseudomonas cepacia from cystic fibrosis patients. The activity of cefepime, both alone and in combination, was comparable to those of other antibiotics. The clinical efficacy of cefepime in cystic fibrosis patients merits investigation. PMID- 1906265 TI - [Oral administration of 1-hexylcarbamoyl-5-fluorouracil (HCFU) in repeated arterial bolus chemotherapy in metastatic liver cancer of humans--preliminary randomized trial]. PMID- 1906266 TI - A study of the effects of phorbol 12-myristate-13-acetate on cell differentiation of pure human melanocytes in vitro. AB - Pure human melanocyte cultures were established in a serum-free medium containing epidermal growth factor (10 ng/ml), hydrocortisone (10(-7) M), insulin (5 micrograms/ml), transferrin (10 micrograms/ml), cholera toxin (2 ng/ml), isobutylmethyl xanthine (10(-4) M) and bovine pituitary extract (30 micrograms/ml). To investigate the biological effects of PMA on melanocytes in vitro, the cells were incubated in media containing various concentration of PMA (including 0 nM, 85 nM and 170 nM), and grown continuously for 12 days without passage. The cells were observed for changes in cell morphology, cell cycle, cytoskeleton and HLA-DR expression. In addition, the effect of PMA on tyrosinase activity was also evaluated. The results revealed that the higher the PMA concentration, the higher the percentage of large irregularly shaped melanocytes. These large melanocytes were three to ten times the size of small bipolar or multipolar cells. A higher concentration of PMA was also associated with a higher percentage of melanocytes in the S and G2-M phases of the cell cycle and with a higher percentage of melanocytes as tetraploid and octaploid karyotypes. The cytoskeleton (vimentin) in the large irregularly shaped cells appeared disaggregated as compared with that in the usual dendritic cells with a compact distribution. HLA-DR was found to be expressed on some melanocytes growing in media containing PMA, appearing both in large dendritic cells and large irregularly shaped cells. None of the cells expressed HLA-DR when cultured in the absence of PMA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1906267 TI - Accidental exposure of children to polychlorinated biphenyls. AB - Children exposed to polychlorinated biphenyls (PCBs) while playing with parts of a capacitor had elevated serum concentrations of lower chlorinated PCBs, similar to Arochlor 1242. These levels declined over 11 months of followup to about half their initial values, from a mean of 12.9 to 6.3 ppb (parts per billion, ng/mL) among four children. In comparison, other persons in the same household and a reference group of persons seen in the same geographic area had serum levels of Aroclor 1242-like PCBs below the limit of detection (less than 5 ppb). All three groups--the children, household members, and geographic referents--also had higher chlorinated PCBs in their serum similar to Aroclor 1260 (HPCBs). HPCB concentrations were similar in these groups (approximately 2 ppb) and did not decline significantly. PMID- 1906268 TI - Neurobehavioral dysfunction in firemen exposed to polychlorinated biphenyls (PCBs): possible improvement after detoxification. PMID- 1906269 TI - Antioxidants stimulate endothelial cell proliferation in culture. AB - The effect of antioxidants on the proliferation of cultured endothelial cells (ECs) were studied. Probucol, a lipid-lowering drug with antioxidant properties, added to the growth medium stimulated the proliferation of ECs. D1-alpha tocopherol (tocopherol), a natural antioxidant, and butylated hydroxytoluene, a synthetic antioxidant also had the same effect on the proliferation of ECs. There was no significant difference in the content of thiobarbituric acid-reacting substances between the probucol-containing growth medium and control medium during the growth assay. Pretreatment of ECs with probucol or tocopherol also enhanced ECs proliferation in medium without any added antioxidants. The addition of free radical scavengers superoxide dismutase, catalase and mannitol to the growth medium did not enhance the proliferation of ECs. These findings indicate that the stimulatory effect on ECs proliferation of antioxidants in the growth medium appears to be unrelated to preventing free radical reactions in the medium itself, but rather may be related to the uptake of antioxidants by ECs. PMID- 1906270 TI - GTP-binding membrane proteins in activated and differentiating T cells. AB - We have earlier reported changes in the GTP binding of several membrane proteins including Gs alpha and Gi alpha during thymic differentiation of T cells. Using an [alpha-32P]GTP-photoaffinity labeling technique we have studied the pattern of GTP binding proteins in activated and resting T lymphocytes and in T cells induced to differentiate by TPA. The GTP binding proteins in mitogen-activated T cells resembled those seen in leukemia T cell lines. Treatment of Jurkat, but not of CCRF-CEM, T cells with TPA caused increased GTP-labeling of a 34 kDa protein and Gi alpha. The GTP labeling pattern in TPA-treated Jurkat cells resembled that in resting T lymphocytes. TPA induced de novo expression of functional TCR/CD3 on CCRF-CEM and downregulation of TCR/CD3 on Jurkat cells but these changes did not correlate with the altered GTP-labeling patterns. PMID- 1906271 TI - Organization of the mouse acid beta-galactosidase gene. AB - Overlapping murine genomic DNA fragments containing the entire cDNA sequence were isolated from a cosmid library prepared from the DBA/2J strain of mice. The gene is more than 80-kb long, consisting of 16 exons. All of the exon-intron boundaries have been defined. The organization of the gene is highly conserved between the murine and human genes at least for the several exons and introns for which information for the human gene is available [Morreau et al., J. Biol. Chem. 264:20655, 1989]. Primer extension and RNase protection experiments indicated the presence of three potential transcription initiation sites, which are preceded by GC-rich SP1 binding sites but without typical TATA or CAT boxes, as is often the case for genes coding for housekeeping proteins. Compared to the cDNA sequence from C57BL/6J mouse, there were five nucleotide polymorphisms in the protein coding region, two of which resulted in altered amino acids. PMID- 1906272 TI - Mapping the human CAS2 gene, the homologue of the mouse brown (b) locus, to human chromosome 9p22-pter. AB - Melanin biosynthesis is a multistep process with the first step being the conversion of L-tyrosine to L-Dopa catalyzed by the enzyme tyrosinase. The enzymes which catalyze the other steps of melanogenesis are not known. One murine pigmentation gene, the brown (b) locus, when mutated, leads to a brown or hypopigmented coat. The b-locus protein has been shown to display catalase activity. The human b-locus, therefore, is designated as CAS2. We used the mouse b-locus cDNA to isolate the human homologue, which in turn, was used to map the CAS2 locus to a human chromosome. The potential CAS2 protein codes for 527 amino acids containing a putative signal sequence and transmembrane domain. The CAS2 protein has primary and probably secondary structures similar to human tyrosinase. The CAS2 was mapped to human Chromosome 9 by somatic cell hybridization and, more specifically, to 9p22-pter by in situ hybridization. The assignment of CAS2 on the human Chromosome 9 extends this region of known homology on mouse Chromosome 4. PMID- 1906273 TI - Direct activation of GTP-binding proteins by venom peptides that contain cationic clusters within their alpha-helical structures. AB - Direct interactions of venom peptides that contained a cysteine-stabilized alpha helical motif within their internal molecules with alpha beta gamma-trimeric GTP binding proteins (G proteins) were studied in reconstituted phospholipid vesicles. Mast cell-degranulating (MCD) peptide stimulated the steady-state rate of GTP hydrolysis catalyzed by the reconstituted G proteins. Synthetic D-MCD peptide, the optical isomer of MCD peptide, was also effective in the activation of G proteins as L-MCD peptide. The stimulations by L- and D-peptides were both abolished in G proteins that had been ADP-ribosylated by pertussis toxin. Charybdotoxin also stimulated, though slightly, the GTPase activity of G proteins. Such a stimulation was, however, not observed upon the incubation of G proteins with other venom peptides such as apamin, sarafotoxin and endothelin. Thus, in comparison of the amino acid sequences of their venom peptides, the extent of the activation of G proteins appeared to be correlated with the number of basic amino acid residues around the alpha-helix. These results suggest that cationic clusters at one side of the alpha-helical surface are more important in the direct activation of G proteins than a specific, alpha-helical structure. PMID- 1906274 TI - N-glycolylneuraminic acid specific lectin from Pila globosa snail. AB - A N-glycolylneuraminic acid-specific lectin (PAL) has been purified from an albumin gland extract of the apple snail, Pila globosa. Purification is conducted on a bovine submaxillary mucin-Sepharose 4B affinity matrix followed by gel filtration on a Sepharose 6B column. The lectin agglutinates rabbit erythrocytes. The hemagglutination activity is dependent on Ca2+ concentration in a significant manner but with a remarkable behaviour. The lectin is a trimeric glycoprotein of native Mr 440 kDa with 25% carbohydrate and is composed of three nonidentical subunits of molecular weights 190, 145, and 105 kDa. It has a pI of 7.0. The lectin exhibits a unique and strict specificity toward N-glycolylneuraminic acid and this phenomenon discriminates it from other known sialic acid binding lectins. The uniqueness indicates the absolute need for a glycolyl substitution on the amino residue and of a glyceryl side chain on the exocyclic part and an axial -COOH group in neuraminic acid. The presence of an acetyl substitution on the exocyclic part impedes lectin-ligand interaction. PMID- 1906275 TI - A fluorescence study of the interactions of benzo[a]pyrene, cytochrome P450c and NADPH-cytochrome P450 reductase. AB - Fluorescence quenching of benzo[a]pyrene (BP) by cytochrome P450c was used to probe this substrate-enzyme binding interaction. Addition of NADPH-cytochrome P450 reductase, an essential electron carrier during P450 catalysis, resulted in increased quenching and thus strengthened binding of BP to P450c. This shows that the role of reductase extends beyond that of an electron transfer agent to influence substrate binding. Fluorescence titration measurements revealed that reductase and P450c formed a complex with an apparent KD of 13.7 +/- 0.9 nM. Reductase had no effect in the presence of an anti-P450c monoclonal antibody which inhibits BP hydroxylation, which suggests that this monoclonal antibody binds P450c near its reductase binding region. PMID- 1906276 TI - The CO2 laser in arthroscopy: potential problems and solutions. AB - The CO2 laser is the most commonly used laser in arthroscopic surgery. This device offers enhanced precision in both cutting and ablation, as well as improved accessibility of difficult to reach structures. However, the use of energy rather than mechanical devices, the lack of tactile feedback, and the necessary use of a gaseous environment can result in problems not encountered in conventional arthroscopic surgery. This article presents these problems and suggests solutions. PMID- 1906277 TI - Primary care teaching physicians' losses of productivity and revenue at three ambulatory-care centers. AB - This study reports two years of basic data concerning University of Illinois clerkship students, their teaching faculty, and their patients at three community health centers. Students from four classes (1985, 1986, 1987, and 1988) were studied in 1985 and 1986. The faculty were family physicians, internists, and pediatricians who provided 20% of the undergraduate medical education for the last 30 months of a four-year curriculum. The study's goal was to develop estimates of the primary care teaching physicians' productivity, to compare them with the productivity of physicians not involved in teaching, and to provide estimates of revenue shortfalls that occurred for the physicians who were teaching. The estimated productivity of the teaching physicians, working 29 hours a week in ambulatory-care settings, was lower by 30-40% when they were teaching medical students than the productivity of nonteaching physicians regionally and nationally. The average patient-care revenue loss for a full-time-equivalent faculty member per full-time-equivalent student for 1985 was estimated to be $27,531 (regional comparison) or $21,143 (national comparison). The corresponding figures for 1986 were $24,294 and $21,525, respectively. The study's results should be useful to those who are planning to establish ambulatory-care delivery systems and also to directors of existing ambulatory-care delivery systems who may be contemplating accepting medical students. PMID- 1906278 TI - Who cares for the elderly? PMID- 1906279 TI - A simple guide for product evaluation. PMID- 1906280 TI - Regulation of the immune response in lymphatic filariasis and onchocerciasis. AB - The persistence of microfilariae in the blood or skin accompanied by a prominent eosinophilia and elevated serum IgE levels are common features of human infection with filarial parasites. In this review Christopher King and Thomas Nutman discuss recent findings on the role of interleukin 4 (IL-4), IL-5 and gamma interferon (IFN-gamma) in the induction of these immediate hypersensitivity responses. They discuss the role of hypersensitivity in immunity, the development of immune tolerance to filarial antigens and suggest that could explain the impaired immune response of some individuals to filarial infections and the persistence of the microfilaremic state. PMID- 1906281 TI - Immunologic mechanisms in secretory otitis media-recent concepts (Part II). AB - Increasing evidence has been accumulated in the last few years associating immunological mechanisms in the pathogenesis of secretory otitis media. If immunological processes were found to be involved in both of the previously accepted experimental pathogenic models (Eustachian tube obstruction; microbiologically induced) of the disease, recently published data has provided evidence for a third, not Eustachian tube- or microbiological-dependent, exclusively immunological, experimental model. This suggests that immunological mechanisms are probably always involved in the pathogenesis of a disease that is known to be multifactorial in origin, and thus eventually make Immunology the single most important factor in secretory otitis media. In the present article these recent concepts are extensively reviewed by the authors. PMID- 1906282 TI - Ethanol drinking following 6-OHDA lesions of nucleus accumbens and tuberculum olfactorium of the rat. AB - Previous studies have shown that lesions of the dopaminergic system in the brain produced by an intracerebroventricular injection of the neurotoxin, 6 hydroxydopamine (6-OHDA), evoke significant changes in ethanol drinking. In the present experiments, dopaminergic systems of Sprague-Dawley rats were lesioned by 6-OHDA infused into either the tuberculum olfactorium or nucleus accumbens, two of the structures implicated in drug-related reinforcement. Prior to the lesion and immediately thereafter, tests for ethanol preference were undertaken in which water was offered in a self-selection situation together with ethanol which was increased in concentration from 3-30% over a 10-day interval. Following the circumscribed ablation of dopaminergic neurons within either the N. accumbens or tuberculum olfactorium, preference for ethanol increased significantly with absolute intakes exceeding 4.0 g/kg at the 7% concentration during the first postlesion drinking test. During the second postlesion preference test, the mean consumption of ethanol exceeded 6.0 g/kg at the 11% concentration and 4.0 to 5.0 g/kg at the 20 and 30 percent concentrations offered to the rats. When adjacent areas just dorsal or lateral to these structures were lesioned by 6-OHDA, no significant change in consumption of ethanol occurred. Thus, it is envisaged that one of the functional roles for the dopaminergic neurons of the N. accumbens and tuberculum olfactorium is to regulate the craving for a drug with addictive liability such as ethanol. As a result of an impairment of normal function of dopamine receptors or a perturbation in the release of this catecholaminergic neurotransmitter, ethanol becomes reinforcing upon repeated exposure. Thus, an addictive-like state consequently ensues. Finally, it is envisaged that the control mechanism underlying the function of the dopaminergic neurons in the medial-basal forebrain is functionally disinhibited in individuals that consume ethanol to the point of abuse. PMID- 1906283 TI - [Esthetic posterior restorations with the indirect method. 2]. PMID- 1906284 TI - [Esthetic posterior restorations with the indirect method. 1]. PMID- 1906285 TI - B-cell selection and tolerance. AB - The B-lymphocyte repertoire can be divided into a primary repertoire of virgin B cells and a secondary repertoire of antigenically experienced cells. Self tolerance requires that neither of these repertoires contains potentially active cells capable of high-affinity, anti-self antibody production. Recent work has proven that both the primary and the secondary repertoire can be functionally purged, and this mechanism may involve failure of appearance of anti-self clonotypes (clonal abortion) or defects in activation (clonal anergy). PMID- 1906286 TI - A specific and potent immunotoxin composed of antibody ZME-018 and the plant toxin gelonin. AB - Murine monoclonal antibody ZME-018 recognizes a 240 Kda glycoprotein present on the surface of most human melanoma cells and on over 80% of human biopsy specimens tested. Gelonin is a ribosome-inactivating plant toxin similar in nature and rivaling the activity of ricin A chain. ZME-018 was coupled to purified gelonin using the reagents SPDP and 2-iminothiolane. The ZME-gelonin conjugate was purified by S-300 Sephacryl and Blue Sepharose chromatography, removing unreacted gelonin and antibody, respectively. PAGE analysis showed that ZME was coupled to 1, 2, or 3 gelonin molecules. The ZME-gelonin conjugate was 10(6)-fold more active than gelonin itself in inhibiting the growth of log-phase human melanoma cells in culture. The immunoconjugate was not cytotoxic to antigen negative T-24 (human bladder carcinoma) cells. Treatment of melanoma cells with recombinant IFN-alpha or TNF substantially augmented the cytotoxicity of the immunoconjugate while treatment with IFN-gamma had a minor effect. Using the human tumor colony assay of melanoma cells obtained from fresh biopsy specimens, greater than 90% growth suppression was observed in 2 of 4 samples tested at a concentration of 250 ng/ml. In addition, 25% growth suppression was observed with a third sample tested, and no growth suppression was observed in 1 sample. Thus, clonogenic melanoma cells are sensitive in vitro to the cytotoxic activity of this immunotoxin at concentrations which we presume are pharmacologically relevant. PMID- 1906287 TI - Cost-effectiveness of antihypertensive drugs. Fact or fancy? PMID- 1906288 TI - Regulation of hepatic cholesterol metabolism in man. AB - The liver is a key element in regulating the amount of low density lipoprotein (LDL) cholesterol in plasma. The interference of cholestyramine treatment in the enterohepatic circulation of bile acids stimulates the activity of the rate limiting enzymatic step in bile acid biosynthesis (cholesterol 7 alpha hydroxylase). This increases demand for cholesterol which is met by enhanced cholesterol biosynthesis (through the enzyme 3-hydroxy-3-methylglutaryl coenzyme A [HMG CoA] reductase) and by an increased expression of LDL receptors. Inhibition of HMG CoA reductase activity by treatment with specific inhibitors such as pravastatin enhances LDL receptor binding activity. Combination of the two treatments results in a significant stimulation of LDL receptor expression and a drastic reduction in the concentration of plasma LDL cholesterol. Thus, selective interference with bile acid enterohepatic circulation and cholesterol biosynthesis may be utilised to regulate plasma lipoprotein metabolism. PMID- 1906289 TI - Interferon-alpha and tumor necrosis factor-alpha in serum of patients in various stages of HIV-1 infection. AB - Serum samples of 120 patients in different stages of chronic human immunodeficiency virus type 1 (HIV-1) infection, 11 patients with primary HIV-1 infection (PHI), and 49 HIV-1 seronegative homosexual men were analyzed for tumor necrosis factor-alpha (TNF-alpha), interferon-alpha (IFN-alpha), and HIV-1 p24 antigen. Increased levels of IFN-alpha and TNF-alpha were found in some, but not all, cases with PHI. During progressing disease IFN-alpha occurred in serum with increasing frequency and concentration. Raised levels of TNF-alpha were found in all stages of chronic infection, but were less common in patients with AIDS than were raised levels of IFN-alpha. The levels of the two substances were not correlated. There was a correlation between IFN-alpha, but not TNF-alpha, and the occurrence of HIV-1 p24 antigen in serum. These results suggest that IFN-alpha and TNF-alpha are induced by different agents during HIV-1 infection. The findings would be consistent with the hypothesis that IFN-alpha and TNF-alpha are counteracting forces that have important down- and upregulatory effects, respectively, on HIV-1 replication in vivo. PMID- 1906290 TI - Virucidal efficacy of various lens cleaning and disinfecting solutions on HIV-I contaminated contact lenses. AB - The virucidal efficacy of various commercially available contact lens care cleaning regimens on human immunodeficiency virus (HIV-1) contaminated contact lenses using either cursory or meticulous cleaning with a rubber policeman was evaluated. Levels of infectious HIV-1 remaining on individual contact lenses were determined by cultivating the lenses with target HUT-78 cells and subsequently analyzing the cultures for the production of HIV-1 p24 by antigen capture and for HIV-1 gag gene DNA content by the polymerase chain reaction. The data indicate that most of the lens care regimens tested, when coupled with meticulous rubbing, were capable of safely decontaminating the contact lenses, that is, they reduce the amount of infectious HIV-1 on the lenses by greater than a 10 log concentration (10(-10], relative to standard controls. Most tested lens care regimens, if properly followed, would virtually eliminate any chance of the lens serving as a vector for HIV. PMID- 1906291 TI - Cytogenetic and cellular characteristics of a human embryonal rhabdomyosarcoma cell line, RMS-YM. AB - A human tumour cell line, designated RMS-YM, was established from a childhood rhabdomyosarcoma. The monolayer cells were polygonal, round or spindle-shaped. The cells became multilayered and formed many focal piles when confluent. RMS-YM became stable with a doubling time of about 30 h and has been maintained for 104 passages to date. Tumourigenicity of the cells was confirmed by heterotransplantation into nude mice. Morphological features were similar to those of the primary tumour, and myofibrils were found by electron microscopy. The expression of desmin and human myoglobin, and high levels of striated muscle system specific enzymes were recognised. Chromosomal analysis revealed possible gene amplification in the form of homogeneously staining regions. Oncogene analysis was performed on the primary tumour and the cell line, but neither N-myc nor N-ras genes were amplified, nor were Ki-ras, Ha-ras or N-ras genes mutated at the 12th, 13th and 61st codons. The RMS-YM cell line may provide a system to identify novel genes which are amplified in rhabdomyosarcoma. PMID- 1906292 TI - Sera from patients with colon, breast and lung cancer induce resistance to lysis mediated by NK cytotoxic factors (NKCF). AB - Natural killer (NK) cells are involved in the antitumoral immunologic mechanism. These cells act through the release of cytotoxic molecules defined as NK cytotoxic factors (NKCF). Inhibitory factors of NK and NKCF mediated lysis have been described in in vitro assays. This study evaluates the induction of resistance to NKCF cytotoxicity by sera from 27 patients with colon, breast and lung cancer. Addition of these sera to the cytolytic assay where K562 cells and concentrated NKCF were used, induced resistance to NKCF mediated cytotoxicity in 21 cases (77%). The sera from the group with metastasis blocked NKCF lysis more markedly than the group with local tumours. However, no differences were observed when the groups with colon, breast and lung cancers were compared. This blocking effect was not found to be related to gamma interferon (IFN) levels. In a previous study, we described a tumour factor (NK-RIF) produced by human cell lines derived from metastatic adenocarcinomas. This factor blocked lysis of tumour target cells by NK cells. Consequently, it is proposed that the release of similar tumour factors with a capacity to induce resistance to NKCF may be involved in tumour growth and metastatic spreading in in vivo. PMID- 1906293 TI - Growth inhibition observed following administration of an LHRH agonist to a clonal variant of the MCF-7 breast cancer cell line is accompanied by an accumulation of cells in the G0/G1 phase of the cell cycle. PMID- 1906295 TI - Scutari Press: spreading the word. PMID- 1906294 TI - Success in a man's world. Interview by Alex Mathieson. PMID- 1906296 TI - Environmental issues: how green is my hospital? PMID- 1906297 TI - Conjunctival swabs: assessment of value. PMID- 1906298 TI - Quality of life: the patient's perspective. AB - The quality of life for long-term psychiatric patients in the community is an area of concern for those charged with their care. Variability in community mental health services suggests that those discharged from large psychiatric hospitals may experience a deterioration in life satisfaction. In this article, the authors describe a study designed to provide a baseline by which patients' perceptions of life in hospital could be comprehensively compared with community life after discharge. PMID- 1906299 TI - Preventing post-natal depression. AB - The plethora of anxieties and discomforts which can accompany women throughout pregnancy, childbirth and the early stages of motherhood may not be sufficiently addressed in 'traditional' parent-craft teaching. Debbie Okpala describes the small study she organised which aimed first to identify and then ameliorate the problems which, if left unattended, can predispose to the development of post natal depression. While wider conclusions cannot be drawn from her work, the success she achieved with this particular group of women stands as testimony to her perception and commitment. PMID- 1906300 TI - Proposal for change. PMID- 1906301 TI - Career development. Planning a study visit. PMID- 1906302 TI - RCN management. A positive environment. PMID- 1906303 TI - RCN management. Leadership is about change. PMID- 1906304 TI - Management. Entering the marketing age. PMID- 1906305 TI - Management. Independent perspectives. PMID- 1906306 TI - Management. Recruit, retain, return. PMID- 1906307 TI - Art as therapy: emotional rescue. Interview by Charlotte Alderman. PMID- 1906308 TI - 'Hilarium: joy de veal'. PMID- 1906309 TI - Focus on Wales. On extended loan only. Interview by Linda Thomas. PMID- 1906310 TI - Women in Europe: a successful Europe must close the gap. PMID- 1906311 TI - Using Doppler to diagnose leg ulcers. PMID- 1906312 TI - Family therapy in a rehabilitation hostel. PMID- 1906313 TI - ECG file. Continuous ECG monitoring. PMID- 1906314 TI - Why nurses leave the profession. Part 2. PMID- 1906315 TI - Patient education in coronary care. PMID- 1906316 TI - A pilot project for health care assistants. PMID- 1906317 TI - Fighting talk. PMID- 1906318 TI - AIDS focus. Sticks and stones break my bones. PMID- 1906319 TI - AIDS focus. Anguish in a land of smiles. PMID- 1906320 TI - AIDS focus. Nursing beliefs and pain management. PMID- 1906321 TI - AIDS focus. HIV roundup. PMID- 1906322 TI - Informatics for the uninitiated. PMID- 1906323 TI - Welsh focus. Shouts from the sidelines. PMID- 1906324 TI - Managing liver disease in adults. PMID- 1906325 TI - Community nursing: the case for an allergy service. PMID- 1906326 TI - Why nurses leave the profession. Part 3. PMID- 1906327 TI - Ethics: the nurse's role in relation to advocacy. PMID- 1906328 TI - Clinical environments can be both forbidding and foreboding for the client. PMID- 1906329 TI - Rationing health care. PMID- 1906330 TI - Lateral thinking. Interview by John Naish. PMID- 1906331 TI - Working parents: adopting unfair policies. PMID- 1906332 TI - A day in the life--ear waxing lyrical. PMID- 1906333 TI - Continuing education: a load of PREPP. PMID- 1906334 TI - Blacklisting: send off foul referees. PMID- 1906335 TI - Ethics: confidence trick? PMID- 1906336 TI - Quality care: nursing standards stranded. PMID- 1906337 TI - Peculiar practice nurses. PMID- 1906338 TI - ICN reports on nursing shortages and death-in-childbirth rates. PMID- 1906339 TI - Bladder cancer: long-term follow-up results of patients treated with radical radiation. AB - Carcinoma of the bladder is commonly treated for cure with external beam radiation. Whilst short-term results are associated with a good chance of disease control there is little information about the long-term results of such therapy. We present a retrospective review of the Princess Margaret Hospital experience in treating transitional cell carcinoma of the bladder and emphasis on the long-term follow-up of patients treated with radiotherapy (XRT). Between 1972 and 1980, 355 patients were treated with a radical course of external beam radiation. The overall survival was 20% at 10 years and the cause-specific survival was 32%. Radiation treatment resulted in a long-term bladder preservation in at least 25% of patients. The majority of long-term survivors without evidence of relapse were patients with T1 (solitary tumours), T2 and T3a tumours. This subgroup represents patients with disease favourable for treatment with radiation. Factors affecting response to the XRT and survival included T stage and tumour bulk. Radiation complications were frequent and were usually associated with local disease recurrence. PMID- 1906340 TI - Management of soft tissue sarcomas in Portsmouth 1965-1985. AB - This paper describes the results of combined surgical and radiotherapy management of 118 patients with soft tissue sarcoma referred to the Department of Radiotherapy and Oncology at Portsmouth between 1965 and 1985. After exclusion of paediatric rhabdomysarcomas, tumours of the gastrointestinal tract and patients who were referred for follow-up only, 109 patients were left for retrospective analysis: 23 patients had surgery only, 11 received a course of preoperative radiotherapy, 52 were irradiated postoperatively and 14 had only radiotherapy. A range of doses and fractionations was used. The total 5-year actuarial survival was 39.7%, the disease-free survival was 35.6%. After excluding Kaposi sarcomas, retroperitoneal tumours, patients with distant metastases or those too ill for radical therapy, the respective figures were 55.5% and 49.7%. If we also excluded patients, treated by radiotherapy only, or irradiated with gross postoperative disease, the figures were 62.7% and 57.3% respectively. Five-year actuarial local control in 68 patients irradiated either without surgery, or postoperatively, was 57.2%. In tumours smaller than 5 cm in diameter, 5-year survival was 86.7%, and local control was 93.3%. For large tumours over 10 cm in diameter, the respective values were 22.2% and 50%. The dose of 60 Gy was satisfactory, if the surgical procedure removed all macroscopical disease, but higher doses are recommended when there is clinically apparent residual disease. PMID- 1906341 TI - Molecular and cytogenetic analysis of tumors in von Recklinghausen neurofibromatosis. AB - Von Recklinghausen neurofibromatosis (NF1) is a common autosomal dominant disorder mapped to 17q11.2 and typically characterized by the occurrence of neural crest-derived tumors. The gene has recently been cloned using reverse genetics or "positional cloning" approaches. Its function, however, remains unknown. We have performed cytogenetic and molecular analyses on 9 malignant tumors from NF1 patients to look for loss of alleles or chromosome rearrangements involving chromosome 17 to test the hypothesis that the NF1 gene acts as a recessive "tumor suppressor" gene. Loss of alleles on this chromosome was detected for 3 of 9 malignant tumors. Two peripheral nerve sheath tumors showed allele loss at informative loci on both the long and short arms of chromosome 17. In contrast, a glioblastoma with focal gliosarcoma showed loss of heterozygosity on the short arm of chromosome 17 only, and not at loci on the long arm. One nerve sheath tumor was previously shown by direct sequence analysis to have a point mutation at the TP53 locus at 17p13. These data support a role for the TP53 gene or other genes on the short arm of chromosome 17 in at least some malignancies in NF1. Six other neurofibrosarcomas showed no allele loss at informative loci on chromosome 17. Cytogenetic analysis was performed on 7 tumors, including 2 with allele loss. The two tumors with allele loss showed abnormal karyotypes while all others were normal. Southern blot and pulsed-field gel analysis using probes within or closely linked to the NF1 locus detected no gross deletions or rearrangements in the tumors studied.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1906342 TI - Immunoglobulin gene rearrangements in acute lymphoblastic leukemia with the 9;11 translocation. AB - The recurring chromosomal 9;11 translocation [t(9;11) (p22;q23)] typically is associated with acute monoblastic leukemia, but a number of patients with acute lymphoblastic leukemia also have been reported to have the t(9;11). To investigate the cell lineage in the latter cases, we analyzed DNA from the leukemic cells of an 8-year-old girl with acute lymphoblastic leukemia and a t(9;11) for rearrangements of the immunoglobulin and T-cell receptor genes. Rearrangements of both immunoglobulin heavy-chain loci and of one lambda light chain gene were detected, as well as deletions affecting both alleles of the kappa light-chain genes; T-cell receptor genes were in germline configuration. These results provide further evidence that the 9;11 translocation is not limited to myeloid lineage leukemia and may be observed in acute lymphoblastic leukemia. PMID- 1906343 TI - Structural alterations in the 5' region of the BCL2 gene in follicular lymphomas with BCL2-MBR or BCL2-MCR rearrangements. AB - We report a new class of molecular lesions in the 5' region of the BCL2 protooncogene when it undergoes a t(14;18) translocation-associated rearrangement in the major break cluster (MBR) or minor break cluster (MCR) regions. Among 52 tumors assayed for BCL2 rearrangements using the MBR, MCR, and 5' probes, seven (six with MBR and one with MCR translocation breaks) showed aberrant bands in unique enzyme digests of DNA hybridized with the 5' probe. The aberrant bands in four tumors were in HindIII digests, in two they were in EcoRI digests, while the aberrant band in one was in a BamHI digest. The two EcoRI bands and two of the four HindIII bands were of identical sizes. Germline polymorphisms as the source of these bands was ruled out by appropriate control experiments. These results suggest that the bands were derived from point mutations or small deletions in the 5' region of BCL2. The significance of this alteration to BCL2 function in translocation-carrying tumors remains to be determined. PMID- 1906344 TI - Transcriptional deregulation of myc in IgH/myc 6;7 translocation carrying rat immunocytomas. AB - We have previously shown that the reciprocal translocation t(6;7) associated with the spontaneous immunocytoma of the Louvain rat (RIC) leads to the juxtaposition of myc to the IgH cluster. In 10 of 14 tumors investigated the breakpoints on the myc carrying chromosome were clustered in a 1.5 kb region 5' of the intact gene, proximal to the myc promoters. In this paper we describe the effect of the translocation on myc transcription in the RIC system. Run-on analysis showed transcriptional attenuation in the normal rat myc gene, similar to the situation in mice and humans. The attenuation was almost completely abrogated in the three immunocytomas studied. Sequence analysis of two tumors failed to reveal any structural changes within exon 1, as found by others in Burkitt's lymphoma. We also show that the transcriptional initiation of myc mRNA is changed in the RICs. In an established line of rat fibroblasts (Rat-2), the more distal myc promoter (P2) is the preferred site of initiation. In RIC, however, only 30% of transcripts were initiated from P2. We found that 40% of the transcripts were initiated from P1 and 30% from a novel promoter, designated P1a, located between P1 and P2. PMID- 1906345 TI - Polypeptide backbone resonance assignments and secondary structure of Bacillus subtilis enzyme IIIglc determined by two-dimensional and three-dimensional heteronuclear NMR spectroscopy. AB - The enzyme IIIglc-like domain of Bacillus subtilis IIglc (IIIglc, 162 residues, 17.4 kDa) has been cloned and overexpressed in Escherichia coli. Sequence specific assignment of the backbone 1H and 15N resonances has been carried out with a combination of homonuclear and heteronuclear two-dimensional and heteronuclear three-dimensional (3D) NMR spectroscopy. Amide proton solvent exchange rate constants have been determined from a series of 1H-15N heteronuclear single-quantum coherence (HSQC) spectra acquired following dissolution of the protein in D2O. Major structural features of IIIglc have been inferred from the pattern of short-, medium- and long-range NOEs in 3D heteronuclear 1H nuclear Overhauser effect 1H-15N multiple-quantum coherence (3D NOESY-HMQC) spectra, together with the exchange rate constants. IIIglc contains three antiparallel beta-sheets comprised of eight, three, and two beta-strands. In addition, five beta-bulges were identified. No evidence of regular helical structure was found. The N-terminal 15 residues of the protein appear disordered, which is consistent with their being part of the Q-linker that connects the C terminal enzyme IIIglc-like domain to the membrane-bound IIglc domain. Significantly, two histidine residues, His 68 and His 83, which are important for phosphotransferase function, are found from NOE measurements to be in close proximity at the ends of adjacent strands in the major beta-sheet. PMID- 1906346 TI - Alternatively folded states of an immunoglobulin. AB - Well-defined, non-native protein structures of low stability have been increasingly observed as intermediates in protein folding or as equilibrium structures populated under specific solvent conditions. These intermediate structures, frequently referred to as molten globule states, are characterized by the presence of secondary structure, a lack of significant tertiary contacts, increased hydrophobicity and partial specific volume as compared to native structures, and low cooperativity in thermal unfolding. The present study demonstrates that under acidic conditions (pH less than 3) the antibody MAK33 can assume a folded stable conformation. This A-state is characterized by a high degree of secondary structure, increased hydrophobicity, a native-like maximum wavelength of fluorescence emission, and a tendency toward slow aggregation. A prominent feature of this low-pH conformation is the stability against denaturant and thermal unfolding that is manifested in highly cooperative reversible phase transitions indicative of the existence of well-defined tertiary contacts. These thermodynamic results are corroborated by the kinetics of folding from the completely unfolded chain to the alternatively folded state at pH 2. The given data suggest that MAK33 at pH 2 adopts a cooperative structure that differs from the native immunoglobulin fold at pH 7. This alternatively folded state exhibits certain characteristics of the molten globule but differs distinctly from it by its extraordinary structural stability that is characteristic for native protein structures. PMID- 1906347 TI - Photodependent inhibition of rat liver NAD(P)H:quinone acceptor oxidoreductase by (A)-2-azido-NAD+ and (A)-8-azido-NAD. AB - Two photoaffinity analogues of NAD+, (A)-2-azido-NAD+ [nicotinamide 2 azidoadenine dinucleotide] and (A)-8-azido-NAD+ [nicotinamide 8-azidoadenine dinucleotide], have been synthesized, and their reactivities with the rat liver NAD(P)H:quinone acceptor oxidoreductase have been investigated. The reduce nicotinamide nucleotide probes, (A)-2-azido-NADH and (A)-8-azido-NADH, were shown to be substrates of the quinone reductase. This enzyme was inhibited by (A)-8 azido-NADH, were shown to be substrates of the quinone reductase. This enzyme was inhibited by (A)-2-azido-NAD+ and (A)-8-azido-NAD+ in a photodependent manner, and the inhibition of the enzyme could be prevented by the presence of nicotinamide nucleotide substrates during photolysis. (A)-2-Azido-NAD+ was demonstrated to be a more potent inhibitor than (A)-8-azido-NAD+. In addition, the photodependent inhibition by (A)-8-azido-NAD+ increased when menadione, the substrate of the enzyme, was present during the photolysis, while menadione protected the enzyme from the photodependent inhibition by (A)-2-azido-NAD+. These results indicate that these two NAD+ analogues can be used to identify the nicotinamide nucleotide binding site of this quinone reductase and that they probably bind to the enzyme in different fashions. PMID- 1906348 TI - [Cost-effectiveness of nutritional support]. PMID- 1906349 TI - [Cost-effectiveness of individualized enteral nutrition by a nutrition support team in laryngectomized cancer patients]. AB - The purpose of this study was to evaluate the effectiveness of a Nutritional Support Team (NST) in the control and follow-up of enteral nutrition (EN) in patients subjected to laryngectomy as a result of neoplasia. The study was performed on two groups of patients (A and B) who had been admitted into the Otorhinolaryngological Department, and who required EN by nasogastric tube during the postoperative period. Group A consisted of 20 patients in whom EN was based on standard guidelines, with a daily intake of 11.1 g of Nitrogen and 2.000 kcals. Group B included 23 patients who received EN individually, using NST with a daily intake of Nitrogen of between 8 and 21 g, and energy intake of between 2.000 and 3.000 kcals. The total cost of nutrition was calculated using the following partial costs: diet, administration, laboratory analysis and NST head responsible for follow-up of Group B. Individualized EN was more effective in nutritional terms than a standard diet in all patients. Using this form of treatment, positive Nitrogen balance were achieved, levels of seric albumin were maintained as well as weight, and complications were reduced. The average cost of nutrition per patient in Group B was 46.258 pesetas and in Group A, 43.963 pesetas. However, in the latter Group, there was an average additional weight loss of 4 kg per patient, and an increase in cost effectiveness ratio of 573 pesetas in weight gained in Group B compared to Group A. PMID- 1906350 TI - Development of a luminescence immunoassay for follitropin suitable for clinical routine. AB - We developed a luminescence immunoassay (LIA) for follitropin, based on the synthesis of a follitropin-N-(4-aminobutyl)-N-ethylisoluminol conjugate. The luminescence tracer was purified by gel chromatography. Antibody-bound and non bound tracer fractions were separated by using a second antibody reagent bound to magnetic particles. The assay can be performed within 24 hours and is sufficiently sensitive for the measurement of all clinically relevant follitropin concentrations including the subnormal range. PMID- 1906351 TI - Comparative thrombolytic properties of bolus injections and continuous infusions of a chimeric (t-PA/u-PA) plasminogen activator in a hamster pulmonary embolism model. AB - The recombinant chimeric plasminogen activator, rt-PA-delta FE/scu-PA-e, consisting of amino acids 1 to 3 and 87 to 274 of tissue-type plasminogen activator (t-PA) and amino acids 138 to 411 of single-chain urokinase-type plasminogen activator (scu-PA), has a markedly increased thrombolytic potency following its continuous intravenous infusion in animal models of venous thrombosis (Collen et al, Circulation, in press). In the present study, the thrombolytic potencies of intravenous bolus injections of rt-PA-delta FE/scu-PA e, of recombinant t-PA (rt-PA), and of recombinant scu-PA (rscu-PA), given alone or in combination, were compared with those of intravenous infusions in a hamster pulmonary embolism model. Dose-dependent clot lysis was obtained in the absence of systemic activation of the fibrinolytic system and fibrinogen breakdown. In bolus injection experiments, the maximal rate of clot lysis, expressed in percent clot lysis per milligrams per kilogram compound administered, was 120 +/- 10 for rt-PA, 54 +/- 8 for rscu-PA, and 2,100 +/- 500 for rt-PA-delta FE/scu-PA-e (P less than .01 v rt-PA or rscu-PA). Comparative results with continuous infusion over 1 hour were 270 +/- 64, 99 +/- 18, and 1,500 +/- 250 (P less than .01 v rt PA or rscu-PA) percent lysis per mg/kg compound infused for rt-PA, rscu-PA, and rt-PA-delta FE/scu-PA-e, respectively. Thus, rt-PA and rscu-PA are more potent when administered as an infusion than as a bolus, whereas rt-PA-delta FE/scu-PA-e is at least as potent when administered as a bolus. Combined bolus injections of rt-PA and rscu-PA had a 2.2-fold synergistic effect on clot lysis, but no synergism was observed with combined bolus injections or with combined infusions of rt-PA and rt-PA-delta FE/scu-PA-e, or of rscu-PA and rt-PA-delta FE/scu-PA-e. The present study thus shows that rt-PA-delta FE/scu-PA-e is much more potent for clot lysis than rt-PA or rscu-PA when administered as a bolus injection, but no synergistic interaction is observed between the chimera and either rt-PA or rscu PA. PMID- 1906352 TI - Interferon-alpha overrides the deficient adhesion of chronic myeloid leukemia primitive progenitor cells to bone marrow stromal cells. AB - Primitive blast colony-forming cells (BI-CFC) from chronic myeloid leukemia (CML) patients are defective in their attachment to bone marrow-derived stromal cells compared with normal BI-CFC. We investigated the effect of recombinant interferon alpha 2a (IFN-alpha) on this interaction between hematopoietic progenitor cells and bone marrow-derived stromal cells by culturing normal stromal cells with IFN alpha (50 to 5,000 U/mL). At 50 U/mL we found that: (1) the capacity of stromal cells to bind two types of CML primitive progenitor cells (BI-CFC and long-term culture-initiating cells) was increased; and (2) the amount of sulfated glycosaminoglycans (GAGs) in the stromal layer was increased. However, sulfated GAGs were not directly involved in binding CML BI-CFC, unlike binding by normal BI-CFC, which is sulfated GAG-dependent. Neuraminidase-treated control stromal cells bound an increased number of CML BI-CFC, reproducing the effect of IFN alpha, whereas the binding to IFN-alpha-treated stromal cells was unaffected by neuraminidase treatment. Thus, the enhanced attachment by primitive CML progenitor cells to INF-alpha-treated stromal cells might be due to changes in the neuraminic acid composition in the stromal cell layer. Our in vitro evidence may provide insights into the mechanism of action of IFN-alpha in vivo. Prolonged administration may alter the marrow microenvironment in some patients such that it can restrain the aberrant proliferation of Philadelphia chromosome (Ph) positive stem cells while permitting Ph-negative stem cells to function normally. PMID- 1906353 TI - Neuropeptide-Y innervation of the rat spleen: another potential immunomodulatory neuropeptide. AB - Neuropeptide-Y (NPY) is a 36 amino acid peptide that acts as a chemical messenger in the central and peripheral nervous systems. NPY often is found colocalized with the classical neurotransmitter norepinephrine (NE) and can potentiate the effects of this neurotransmitter postsynaptically in many systems. Using immunocytochemistry for NPY and specific lymphoid cell markers, we mapped the distribution of NPY-positive nerve fibers in the rat spleen. NPY-positive nerve fibers were present along the vasculature, trabeculae, and capsule, and also were found associated with specific lymphoid parenchymal compartments of the spleen, in close contact with lymphocytes and macrophages. These contacts were investigated further at the electron microscopic level. NPY-positive nerve terminals were found in close apposition with lymphocytes in the periarteriolar lymphatic sheath, and with lymphocytes and macrophages in the marginal zone. Previous studies have reported that postganglionic noradrenergic nerve fibers innervate specific lymphoid compartments of the rat spleen, with nerve terminals forming direct appositions with cells of the immune system. The possible colocalization of NPY and NE in these nerve fibers was investigated by chemical sympathectomy with 6-hydroxydopamine, followed by immunocytochemical labeling of NPY and tyrosine hydroxylase (TH), the rate-limiting enzyme in norepinephrine synthesis. Colocalization also was investigated by labeling for NPY with a fluorescent label, eluting the NPY, and staining for TH with diaminobenzidine as the label. These studies demonstrate that norepinephrine and NPY are colocalized in the postganglionic sympathetic nerve fibers of the rat spleen.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1906354 TI - [Indications for sonography and follow-up studies. Initial results of a prospective study]. AB - Ultrasonic examinations of the abdomen may result in expensive secondary imaging examinations. This prospective study was conducted in collaboration with the Zentralinstitut Koln. The first aim of our study was to compare the results of abdominal sonography in three different patient groups: The first group was comprised of patients referred for a medical check-up, the second group of patients referred because of upper abdominal pain and the third group of patients with generalized atherosclerosis. The second aim was to correlate sonographic findings (classified in three degrees of severity), with subsequently induced diagnostic procedures in the three groups. 2719 patients were enrolled, 2393 (88%) in group 1, 286 (11%) in group 2 and 40 (1%) in group 3. A total of 1792 abnormal findings were diagnosed. 65.6% of the findings in group 1, 65.7% in group 2 and 88% in group 3 were abnormal. Up to now, the findings led to a nearly equal number of subsequent diagnostic procedures in groups 1 and 2. The preliminary results show that abdominal sonography may be as effective in patients for a check-up as in patients referred because of a well-defined indication. Patients with defined abdominal symptoms show more abnormal sonographic findings than patients on a check-up. Higher costs resulting from subsequent examinations deserve critical assessment in the individual patient. PMID- 1906355 TI - Thrombotic thrombocytopenic purpura following allogeneic bone marrow transplantation. PMID- 1906356 TI - Aerosolized pentamidine for prevention of Pneumocystis pneumonia after allogeneic marrow transplantation. PMID- 1906357 TI - Exacerbation of inflammatory demyelinating polyneuropathy after bone marrow transplantation. AB - Two patients with hematologic malignancy and quiescent inflammatory demyelinating polyneuropathy developed severe exacerbations of polyneuropathy at the time of bone marrow transplantation. The clinical course in both patients was progressive despite therapy with immuno-suppressive agents, plasmapheresis, and high dose immunoglobulin. The polyneuropathy resulted in quadriplegia which contributed to the patients' deaths 175 and 48 days after transplantation. Sections of multiple peripheral nerves sampled post mortem in the first case revealed prominent demyelination with heavy infiltration of macrophages and lymphocytes. Immunohistochemical studies demonstrated that most of the lymphocytes were of the CD8+, cytotoxic/suppressor cell class and that many of the Schwann cells expressed class II (HLA-DR) antigen. This report suggests that bone marrow transplantation can exacerbate inflammatory demyelinating polyneuropathy. PMID- 1906358 TI - Performance of a commercially available field flatness device. PMID- 1906359 TI - Early abdominal complications following heart and heart-lung transplantation. AB - In the first 11 years of the heart and heart-lung transplantation programme at Papworth Hospital, Cambridge, 356 patients underwent heart transplantation, and 73 patients received both heart and lungs. Out of 429 patients 41 (9.5 per cent) developed abdominal complications within the first 30 days, and 20 of the 41 required surgery. The complications included pancreatitis (10), peptic ulceration (8), and pseudo-obstruction (8), in addition to colonic perforation and small bowel obstruction. When laparotomy was performed it was well tolerated. This paper supports the view that successful management of abdominal complications following transplantation requires prompt diagnosis and treatment. Where doubt exists in the presence of an acute abdomen, laparotomy is the appropriate way to establish a definitive diagnosis. PMID- 1906360 TI - Modulation of brown adipose tissue-mediated thermogenesis by lesions to the nucleus tractus solitarius in the rat. AB - Given that relatively little is known regarding the central control of brown adipose tissue (BAT)-mediated thermogenesis the present study assessed whether the direct pharmacological stimulation of beta- or alpha-adrenergic receptors located on the brown adipocytes would result in a typical thermogenic response following electrolytic lesions to the nucleus tractus solitarius (NTS). Bilateral electrolytic lesions to the NTS in the rat effectively disrupted the baroreceptor reflex arc. It was observed that the metabolic and temperature responses to either norepinephrine (1, 5, or 25 micrograms/kg/min) or to the beta-agonist isoproterenol (0.5 micrograms/kg/min) were significantly attenuated in the NTS lesioned rats relative to the control animals with an intact baroreflex. Conversely, the cardiovascular effects of norepinephrine or of the alpha-agonist phenylephrine (10 micrograms/kg/min) were enhanced in the NTS-lesioned animals. The results suggest that the functional capacity of the brown adipocytes was reduced following NTS lesions and points to an alteration in the ability of beta receptors to respond to pharmacological stimulation with a typical thermogenic response. PMID- 1906361 TI - Influence of Ca2+ on synaptic morphology of fish cone photoreceptors. AB - Isolated fish retinas were incubated with the Ca(2+)-ionophore A23187 at various Ca2+ concentrations. Computer reconstructions of the ultrastructure of cone synapses revealed pronounced reduction of the presynaptic surface (complete loss of the synaptic invaginations) in response to low intracellular Ca2+ (less than 10(-8) M). No obvious effect on synaptic morphology was noticed at Ca2+ greater than 10(-8) M. Ca(2+)-dependent exocytotic activity appears to be a major factor controlling the invaginated morphology of cone synapses. PMID- 1906362 TI - [Immunohistochemical localization of transforming growth factor-beta (TGF-beta) in smooth muscle tissue]. AB - Anti-TGF-beta antibodies were raised in rabbits against a C-terminal synthetic peptide whose amino acid sequence was chosen after human TGF-beta 1 primary sequence antigenic study by continuous epitope prediction. Immunopurified antibodies were used for an immunohistochemical localization in normal and pathological human tissues. Smooth muscular type tissue seems to be an elective target. PMID- 1906363 TI - [Contraceptive activity of RU486 and oral active prostaglandin combination]. AB - The most used medical method for early pregnancy interruption associates the antiprogestin RU486 (Mifepristone) and an intramuscularly injected prostaglandin (Sulprostone) (Silvestre et al., New Engl. J. Med., 322, 1990, pp. 645-648). Misoprostol, an orally active PGE1 synthetic derivative, showed the same efficacy as Sulprostone in a trial including 100 patients. The medical characteristics and potential of the new method are briefly discussed. PMID- 1906364 TI - [Quantitative imaging of the heterogeneity of membrane activation of mammalian neurons and glial cells]. AB - By using quantitative imaging with an ultra-high sensitivity, it was possible to observe the simultaneous action of multiple patches unevenly distributed over the membranes of neurons and glial cells in culture. We used a voltage-sensitive probe to stain vitally the cells. The instrumentation consisted of a liquid nitrogen cooled matrix of 222,530 photodetectors with a spatial resolution of 0.25 microns 2, a photodynamic range of 10(5), a detection level of a few tens of photons and a maximum time resolution of 500 microseconds. Electrical and pharmacological stimulations were applied to produce the activation of the cells which was accompanied by large variations of the level of fluorescence, giving a precise spatial localization of active domains over the soma-neuritic membranes. These images of fluorescent signals are interpreted as corresponding to the plasmalemmal localization of voltage-dependent channels. This finding, which had not been previously observed with voltage-sensitive probes in fluorescent dye imaging indicates the possibility of measuring the activity of independently functioning domains in single neurons. PMID- 1906365 TI - [Extra-bulbar primary olfactory projection in teleost fishes]. AB - Immunohistochemical investigations with anti-substance P antiserum demonstrate the existence of an extensive extrabulbar primary olfactory projection in several gymnotid teleost fish. This projection, never described before, originates in particular primary olfactory bundles which enter with the olfactory nerve into the olfactory bulb. While the bulk of the olfactory fibers end with glomeruli in the glomerular layer of the olfactory bulb, two particular bundles penetrate into the telencephalon and end, without forming glomeruli, in several telencephalic and diencephalic regions. A few fibers run as far as to the hypothalamus. In the light of these findings, the general notion that the primary olfactory projection is limited to the olfactory bulb and forms only glomeruli-like terminals, should be reconsidered. PMID- 1906366 TI - The effect of tricyclic antidepressants on cortex- and amygdala-kindled seizures in the rat. AB - The anticonvulsant effects of amitriptyline, imipramine, nortriptyline and desipramine were tested against focal and generalized seizures, triggered from either the amygdala or the cortex in fully kindled rats. Tests were administered on a 72- or a 24-hour schedule. Significant seizure suppression was achieved with only one drug, amitriptyline, and it occurred only at toxic or near-toxic doses. The differential, low-dose suppression of amygdala-kindled seizures, reported in earlier studies, was not seen in the present experiments. It may occur only in the short-interval test paradigms used by previous experimenters. PMID- 1906367 TI - DNR policy and CPR practice in geriatric long-term institutional care. PMID- 1906368 TI - High-dose melphalan with 6-hydroxydopamine-purged autologous bone marrow transplantation for poor-risk neuroblastoma. AB - Long-term results are presented of 28 patients who were diagnosed with neuroblastoma at more than 12 months of age and who received melphalan 180 mg/m2 (n = 6) or 240 mg/m2 (n = 22) to consolidate remissions of Stage IV disease or to control refractory disease. Twenty-four patients also received dianhydrogalactitol 180 to 240 mg/m2, and 11 received total body irradiation 450 to 600 cGy. Autologous bone marrow transplantation (ABMT) was performed with marrow that was unpurged (n = 2) or purged ex vivo (n = 26) with 6 hydroxydopamine (6-OHDA) 20 micrograms/ml plus ascorbate 200 micrograms/ml. The median time to an absolute neutrophil count of 500/microliters was 21 days and to self-sustaining platelet counts more than 20,000/microliters, 28 days. One patient required infusion of unpurged reserve marrow. Two groups of patients underwent ABMT: (1) 17 patients (Group I) who were in first remission a median of 7 months after diagnosis; and (2) 11 patients (Group II) who had refractory disease or were in second remission. For Group I, event-free survival was 29% at 12 months and 6% at 24 months post-ABMT. All Group II patients died of disease or ABMT-related toxicity. Overall, of the 28 patients, one is a long-term relapse free survivor; five died of ABMT-related toxicity; ten patients with tumors present at ABMT had progressive disease within 6 months of ABMT; and 12 patients with no measurable disease at ABMT relapsed 4 to 32 months (median, 12) post ABMT. Among the latter, six relapses involved the primary site, and six were restricted to distant sites. These results--in accord with the long-term outcome in other series--suggest that for neuroblastoma high-dose melphalan cannot be relied on to ablate residual disease or to salvage patients with refractory tumors. In addition, the pattern of relapse in several patients could be explained by infusion of incompletely purged autografts; this would support recent laboratory evidence that 6-OHDA/ascorbate is a suboptimal purging method. PMID- 1906369 TI - Intraoperative electron beam radiation therapy for retroperitoneal soft tissue sarcoma. AB - From December 1981 to December 1989, 20 patients with primary or recurrent retroperitoneal sarcoma received 4000 to 5000 cGy of external beam radiation therapy (EBRT) in conjunction with surgical resection and intraoperative radiation therapy (IORT). Seventeen of 20 patients underwent complete (14 patients) or partial (3 patients) resection. Three patients had shown evidence of metastases after EBRT by the time of surgery. The 4-year actuarial local control and disease-free survival rates of the 17 patients undergoing resection were 81% and 64%, respectively. Twelve patients received IORT at the time of resection for microscopic disease (10 patients) or gross residual sarcoma (2 patients). Of the ten patients receiving IORT for microscopic tumor, one patient has died of local failure and peritoneal sarcomatosis and two patients have died of distant metastases only. The remaining seven patients are disease-free. One patient treated for gross residual sarcoma has experienced a local failure 1 year after IORT and is without disease 7 years after salvage chemotherapy. The other patient treated for gross residual sarcoma has died of local failure. Five patients did not receive IORT at the time of resection because of the extensive size of the tumor bed. Three of these patients are disease-free with one patient alive with lung metastases and one patient dying of hepatic metastases. Aggressive radiation and surgical procedures appear to provide satisfactory resectability and local control with acceptable tolerance. PMID- 1906370 TI - Epidemiology of human listeriosis. AB - During the 1980s, investigation of several large epidemics of listeriosis confirmed that transmission of L. monocytogenes in food causes human disease. Progress in laboratory detection and subtyping of the organism has enhanced our ability to compare human and environmental isolates of L. monocytogenes. Transmission by foodborne organisms is now recognized as causing both epidemic and sporadic listeriosis. Continued study of dietary risk factors associated with listeriosis is needed in order to develop dietary recommendations for the expanding population at increased risk of disease. Current research application of new molecular methods to the study of L. monocytogenes may improve the ability to diagnose pregnancy-associated disease and permit the rapid detection and control of L. monocytogenes in the food supply. PMID- 1906372 TI - Gold labeling of urokinase plasminogen activator. Characterization and specific binding in cultured mammalian cells. AB - A colloidal gold-urokinase plasminogen activator complex (u-PAGC) was prepared and characterized. It was used as an ultrastructural marker to study binding sites for urokinase in human and dermal fibroblasts and bovine adrenal endothelial cells in culture. Both the preparation conditions for 15 nm in diameter gold particles and their labeling with urokinase molecules are reported. The complex was stable for at least 4 weeks and had efficient binding and biological activity. Colloidal gold conjugate was observed as single particles or small clusters scattered on the plasma membrane of the cells at 0 degree C and within vesicles in the cytoplasm after a few minutes at 37 degrees C. These data suggest that urokinase-gold complex is a useful marker for the specific labeling of urokinase binding sites. PMID- 1906373 TI - Electron microscopic localization of F-actin in acrosome reacted boar spermatozoa by means of a phalloidin-FITC complex. AB - An immunocytochemical study at the ultrastructural level has been performed in boar spermatozoa in order to clarify the aggregation state of actin before and after the acrosome reaction. A new phalloidin probe has been used to detect F actin: a phalloidin derivative conjugated with FITC, followed by incubation with an anti-FITC antibody. The protein A-gold technique was then applied for the localization of the antigenic sites. Gold particles were localized on the sperm surface only after the acrosome reaction which was induced by the ionophore A23187. PMID- 1906371 TI - Alginate synthesis by Pseudomonas aeruginosa: a key pathogenic factor in chronic pulmonary infections of cystic fibrosis patients. AB - Pulmonary infection by mucoid, alginate-producing Pseudomonas aeruginosa is the leading cause of mortality among patients suffering from cystic fibrosis. Alginate-producing P. aeruginosa is uniquely associated with the environment of the cystic fibrosis-affected lung, where alginate is believed to increase resistance to both the host immune system and antibiotic therapy. Recent evidence indicates that P. aeruginosa is most resistant to antibiotics when the infecting cells are present as a biofilm, as they appear to be in the lungs of cystic fibrosis patients. Inhibition of the protective alginate barrier with nontoxic compounds targeted against alginate biosynthetic and regulatory proteins may prove useful in eradicating P. aeruginosa from this environment. Our research has dealt with elucidating the biosynthetic pathway and regulatory mechanism(s) responsible for alginate synthesis by P. aeruginosa. This review summarizes reports on the role of alginate in cystic fibrosis-associated pulmonary infections caused by P. aeruginosa and provides details about the biosynthesis and regulation of this exopolysaccharide. PMID- 1906374 TI - L-deprenyl (selegiline) added to Sinemet CR in the management of Parkinson's disease patients with motor response fluctuations. AB - L-deprenyl (Eldepryl) added to Sinemet CR in the treatment regimens of seven patients with Parkinson's disease (PD) and therapeutic response fluctuations (RF) allowed a statistically significant reduction in total daily levodopa intake and an increase in the mean interdose interval. Trends were noted towards a reduction in the number of daily "off" periods and an increase in the portion of the waking day spent "on." Three patients suffered an increase in the intensity of their dyskinesias, and discontinued taking deprenyl. Four patients, all of whom reported improved functioning during "off" periods, have continued taking the combination. Sinemet CR and deprenyl can safely be used together in patients with advanced PD, and the combination may result in improved control of motor fluctuations in selected patients. PMID- 1906375 TI - Concentrations of pravastatin and lovastatin in cerebrospinal fluid in healthy subjects. AB - The capability of pravastatin and lovastatin, HMG-CoA reductase inhibitors likely to be taken chronically for hypercholesterolemia, to cross the blood-brain barrier was investigated in normal male volunteers. Lovastatin, which is lipophilic, was detected in cerebrospinal fluid (CSF) at concentrations that may have a pharmacologic effect. Pravastatin, which is hydrophilic, was not detected in CSF. It is concluded that pravastatin may have less potential for causing CNS related side effects than lovastatin. PMID- 1906376 TI - Microbial beta-glucanases different from cellulases. AB - The beta-glucans different from cellulose are the most abundant class of polysaccharides. They are found in microorganisms and higher plants as structural entities of cell wall, as cytoplasmic and vacuolar reserve materials, and as extracellular substances. Enzyme systems capable to hydrolyze beta-glucans are produced by different microorganisms. The occurrence and nature of beta glucanases and their substrates are reviewed. The regulation of biosynthesis of these enzymes, their properties, substrate and product specificities, mode of action and molecular cloning are described. The participation of beta-glucanases in the morphogenetic events of yeast cell is presented. The role and synergism of different types of 1,3-beta-glucanases in microbial cell wall lysis and the potential application for isolation of intracellular materials like proteins, carbohydrates, enzymes and as an analytical tool are discussed in the light of current knowledge. PMID- 1906377 TI - DT-diaphorase activity and mitomycin C sensitivity in non-transformed cell strains derived from members of a cancer-prone family. AB - Non-transformed skin fibroblasts derived from five members of a cancer-prone family and three unrelated healthy volunteers were assayed for their levels of activity of the quinone reductase DT-diaphorase and for their sensitivity to the antitumor quinone mitomycin C (MMC). Previous studies of skin fibroblasts derived from one afflicted member of this family (3437T) demonstrated increased resistance to MMC under aerobic exposure conditions and a reduced level of DT diaphorase. In the present study 3437T cells and a cell strain derived from another afflicted member of the cancer-prone family were found to be hyperresistant to the cytotoxic effects of MMC, and demonstrated negligible DT diaphorase activity (30 +/- 10 nmol/min/mg protein). Cell strains derived from the three other family members demonstrated intermediate DT-diaphorase activity (400-800 nmol/min/mg protein). Enzyme activities of 1800-6000 nmol/min/mg protein were measured in the three control cell strains. A protein that was reactive with a rabbit polyclonal antibody raised against rat DT-diaphorase and corresponded to the known mol. wt of DT-diaphorase was clearly evident in the three control cell strains, but absent in the two MMC-hyperresistant cell strains. This protein was present in intermediate amounts in the remaining members of the cancer-prone family. Southern analysis of DNA isolated from all eight cell strains and restricted with EcoRI demonstrated the presence of a DNA sequence of approximately 15 kb which hybridized to a rat DT-diaphorase cDNA probe. Northern analysis revealed the presence of an RNA species approximately 1200 bp in size, consistent with that for a human DT-diaphorase mRNA, in all cell strains derived from family members. A post-transcriptional defect would, therefore, appear to be responsible for the decreased enzyme activity observed in the resistant cell strains. These results suggest a role for DT-diaphorase in MMC bioactivation and that reduced levels of the protein may be causally related to the cancer-prone tendency of this family. PMID- 1906378 TI - Potent inhibitory effects of suicide inhibitors of P450 isozymes on 7,12 dimethylbenz[a]anthracene and benzo[a]pyrene initiated skin tumors. AB - A single dose of 1-ethynylpyrene (EP), 1-vinylpyrene (VP) or 2-ethynylnaphthalene (EN) was applied to the skin of SENCAR mice 5 min before an initiating dose of 7,12-dimethylbenz[a]anthracene (DMBA) or benzo[a]pyrene (B[a]P) and the development of skin tumors then promoted with biweekly topical applications of 12 O-tetradecanoylphorbol-13-acetate (TPA). The application of EP strongly inhibited the formation of skin tumors initiated by either DMBA or B[a]P in a dose dependent manner. Application of 44 pmol of EP inhibited tumor initiation by 10 nmol of DMBA approximately 25%; application of 440 nmol of EP inhibited tumor initiation by 200 nmol of B[a]P approximately 51%. A high single dose of EP (4.4 44 mumol) nearly eliminated skin tumor initiation by either 10 nmol of DMBA or 200 nmol of B[a]P. Application of VP also inhibited the formation of skin tumors initiated by either DMBA or B[a]P in a dose-dependent manner, but higher doses of VP than of EP were required to produce comparable inhibitions. Application of 44 nmol of VP inhibited tumor initiation by 10 nmol of DMBA approximately 30%; application of 4.4 mumol of VP inhibited tumor initiation by 200 nmol of B[a]P approximately 56%. Application of EN yielded contrasting results. EN inhibited the formation of skin tumors initiated by 10 nmol of DMBA, but the observed dose dependence was minimal; tumors were decreased about 40% by 3.3 mumol of EN and only about 65% by 132 mumol of EN. A high single dose of EN (132 mumol) increased both the mean number of tumors per mouse and the percentage of mice that developed tumors after initiation by 200 nmol of B[a]P. Topical application of 4.4 mumol of EP, 22 mumol of VP or 33 mumol of EN to the skin of SENCAR mice 5 min before a single initiation dose of 2.5 mumol of N-methyl-N'-nitro-N nitrosoguanidine (MNNG) had a minimal inhibitory effect (14-28%) on the development of skin tumors produced by subsequent biweekly promotion with TPA. A single dose of 44 mumol of EP or 132 mumol of EN followed by biweekly applications of TPA did not produce skin tumors; however, a dose of 44 mumol of VP followed by promotion with TPA produced a low but significant number of skin tumors.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1906379 TI - Benzo[a]pyrene diolepoxide-DNA adducts in alveolar macrophages of smokers. AB - The presence of benzo[a]pyrene diolepoxide (BPDE)-DNA adducts was investigated by synchronous fluorescence spectrophotometry in cells recovered by bronchoalveolar lavage from 39 individuals. Pulmonary alveolar macrophages constituted, on average, 90% of these cells. No adduct was detected in samples from non-smokers or ex-smokers, whereas 84.6% of samples from current smokers exhibited typical fluorescence peaks. The samples from four subjects who had stopped smoking during the last 6 months were also positive. A considerable variability was observed in the intensity of signals, which in positive samples was significantly correlated with the number of cigarettes currently smoked but not with the cumulative total of cigarettes smoked during a lifetime. In any case, part of the recorded quantitative variations could not be ascribed to the daily number of cigarettes but probably depended on interindividual variability in smoking habits or in toxicokinetics and metabolism. On the whole, detection of BPDE-DNA adducts in alveolar macrophages, compared to other surrogate cell populations, appears to represent a sensitive and specific biomonitoring tool, assessing the internal dose of inhaled benzo[a]pyrene in the proximity of target cells of the respiratory tract. Exploitation of this end-point in molecular epidemiology and cancer prevention studies warrants further investigation. PMID- 1906380 TI - Selective induction of rat urinary bladder tumors by simultaneous administration of 3,2'-dimethyl-4-aminobiphenyl (DMAB) and butylated hydroxyanisole or butylated hydroxytoluene is associated with increased DMAB-DNA adduct formation. AB - Modification of 3,2'-dimethyl-4-aminobiphenyl (DMAB) multi-organ carcinogenesis by simultaneous treatment with butylated hydroxyanisole (BHA) or butylated hydroxytoluene (BHT) was studied using young and old male F344 rats. Animals, 4 or 54 weeks old, were given DMAB (s.c. injection of 50 mg/kg body wt once a week for 10 weeks) along with BHA (2.0% in diet for 11 weeks) or BHT (1.0% in diet for 11 weeks). The experiments were terminated 55 weeks after the commencement. Combined administration of BHA or BHT with the carcinogen resulted in development of urinary bladder tumors in greater than 90% of both young and old rats thus treated, whereas no tumors were induced in animals given DMAB alone. In contrast, the appearance of preneoplastic lesions in the liver and pancreas was reduced by BHA or BHT treatment. Tumor development (less than 30% incidence) was also evident in the small and large intestines, prostate, preputial glands, skin/subcutis and ear duct, with no modification by BHA or BHT. No ageing effects were evident. The formations of DMAB-DNA adducts, evaluated by the enzyme-linked immunosorbent assay and immunohistochemical staining, correlated well with tumorigenesis in the urinary bladder, liver and pancreas. The selective enhancement of urinary bladder tumor induction by BHA and BHT appeared to be due to both increased DMAB-DNA adduct formation caused by metabolic alteration of DMAB in the liver and increased DNA synthesis in the urothelial cells. PMID- 1906381 TI - Mutagenicity of benzo[a]pyrene bay-region sulfonates. AB - The interaction between the sulfite anion and specific benzo[a]pyrene (B[a]P) derivatives produces a novel class of benzo[a]pyrene sulfonates. (+/-)-7,8,9 Trihydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene-10-sulfonate (B[a]PT-10-sulfonate) is formed in high yields in incubations containing (+/-)-7r,8t-dihydroxy-9t,10t epoxy-7,8,9,10-tetrahydrobenzo[a]pyre ne (anti-BPDE) and sulfite, and sulfite strongly enhances the mutagenicity of the diolepoxide toward Salmonella typhimurium under those conditions. Although B[a]PT-10-sulfonate itself shows little direct mutagenicity over a 1-20 microM concentration range, this reactive bay-region intermediate does enhance the mutagenicity of anti-BPDE in strains TA98 and TA100 by up to 280%. No significant enhancement was seen when up to 20 microM B[a]PT-10-sulfonate was used in concert with another direct-acting mutagen, N-acetoxy-acetylaminofluorene (N-AcO-AAF). The isomeric product derived from sulfite and (+/-)-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene (B[a]P-7,8-diol) is (+/-)-7,8,10-trihydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene-9-sulfonate (B[a]PT 9-sulfonate). Like B[a]PT-10-sulfonate, B[a]PT-9-sulfonate is not mutagenic to strains TA97, TA98 and TA100. This sulfonate exhibited little enhancing activity with anti-BPDE over a 1-20 microM concentration range, but did enhance the mutagenic response of strain TA98 to 0.2 microM N-Aco-AAF by up to 128%. Sulfite, anti-BPDE and B[a]PT-sulfonates were also examined for the ability to induce a forward mutation at the hgprt locus (8-azaguanine resistance) in strains of S.typhimurium. Sulfite caused a marked enhancement of forward mutation due to anti-BPDE in both TA98 and TA100. Surprisingly, concurrent administration of B[a]PT-10-sulfonate with anti-BPDE did not increase the number of mutant colonies. The extensive conversion of anti-BPDE to B[a]PT-10-sulfonate under conditions where sulfite enhances diolepoxide mutagenicity, when coupled with this enhancement of diolepoxide mutagenicity by B[a]PT-10-sulfonate in the reverse mutation assay, supports this novel B[a]P derivative as a mediator of the sulfite-dependent enhancement of B[a]P genotoxicity. Determining why this enhancing effect was not seen when selecting for mutation at the hgprt locus of S.typhimurium will require further study. PMID- 1906382 TI - A new family with chorioretinal dystrophy, spinocerebellar ataxia and hypogonadotropic hypogonadism (Boucher-Neuhauser syndrome). AB - A family is described in which two brothers have spinocerebellar ataxia, hypogonadotropic hypogonadism and chorioretinal dystrophy. This report provides further evidence to support the previous suggestion that this triad of manifestations represents a specific single-gene disorder, designated Boucher Neuhauser syndrome. Analysis of affected individuals shows that neurological signs usually develop during adolescence or young adulthood (range: early childhood-fourth decade) and are slowly progressive or non-progressive, whereas ophthalmologic manifestations have an age of onset which varies from the first to the sixth decade of life and a pronounced variability in progression. PMID- 1906383 TI - Effects of granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-2, interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha) and IL-6 on the production of immunoreactive IL-1 and TNF-alpha by human monocytes. AB - The effects of GM-CSF, IL-2, IFN-gamma, TNF-alpha and IL-6 on the production of IL-1 (both secreted and cell associated) and TNF-alpha by peripheral blood monocytes were studied. Monocytes were cultured for 20 h in suspension and in serum-free conditions which minimized background stimulation of monokine production. GM-CSF, IL-2 and TNF-alpha directly induced the production of cell associated IL-1 but little or no IL-1 or TNF-alpha secretion. Combination of GM CSF with IFN-gamma, IL-2 or TNF-alpha synergistically enhanced IL-1 secretion and had an additive effect on cell-associated IL-1 production. Combination of IL-2 with IFN-gamma or TNF-alpha also synergistically enhanced IL-1 secretion but the effect on cell-associated IL-1 production was less than additive. GM-CSF synergistically enhanced TNF-alpha secretion induced by IFN-gamma but not by lipopolysaccharide. GM-CSF did not enhance TNF-alpha secretion induced by IL-2 or TNF-alpha. In contrast, IL-2 synergistically enhanced TNF-alpha secretion induced by IFN-gamma. These results are discussed in relation to cytokine involvement in rheumatoid arthritis. PMID- 1906384 TI - Differential control of mesangial cell proliferation by interferon-gamma. AB - Rat mesangial cells were shown to be sensitive to recombinant interferon-gamma (IFN-gamma). IFN-gamma reduced thymidine uptake by these cells and inhibited cell proliferation. Incubation of the cells with 1000 U/ml IFN-gamma decreased thymidine uptake by up to 64% and cell numbers were decreased by 17%. The effects of IFN-gamma were dose and time dependent and were partially reversible by the anti-IFN-gamma monoclonal antibody DB-1. This lymphokine did not reduce incorporation of RNA and protein precursors however. Measurements of 3H-uridine and 3H-leucine incorporation indicated significant increases in RNA and protein synthesis (37% and 45%, respectively) on a per cell basis. The mitogenic effects of IL-1 and platelet-derived growth factor (PDGF) were also susceptible to IFN gamma-mediated inhibition but the mitogenic response to epidermal growth factor (EGF) was much less sensitive. We conclude that while IFN-gamma may act to modulate the mitogenic signals provided by some factors such as IL-1 and PDGF, the response to EGF appears to be unaffected. PMID- 1906385 TI - Naturally occurring anti-interferon-alpha 2a antibodies in patients with acute viral hepatitis. AB - The occurrence of antibodies against recombinant human interferon-alpha 2a (IFN alpha 2a) in patients with acute viral hepatitis (AVH) was examined by ELISA. Naturally occurring IgG anti-IFN-alpha 2a were found in 50% of patients with type A, 50% of those with type B and in 8.3% of those with non-A, non-B AVH. The corresponding frequencies of IgM antibodies were 80%, 30% and 33.3%, respectively. IgM anti-IFN-alpha 2a were found more frequently in patients with AVH type A than in normal control subjects (P less than 0.01). Anti-IFN-alpha 2a were detectable at the highest frequency 3 weeks after acute onset and then became negative. An absorption experiment revealed that IgM anti-IFN-alpha 2a did not cross-react with recombinant human IFN-alpha 2b. Immunoblotting analysis confirmed the binding of antibodies to IFN-alpha 2a. Sera positive for IgG and/or IgM anti-IFN-alpha 2a were unable to neutralize IFN-alpha 2a. The appearance of anti-IFN-alpha 2a was not correlated with disease severity. There was no evidence to suggest that anti-IFN-alpha 2a impaired the elimination of hepatitis virus. This is the first study to demonstrate the occurrence of anti-IFN-alpha 2a in patients with AVH. Detection of anti-IFN-alpha 2a may be useful for clarifying any underlying immune events in various diseases. PMID- 1906386 TI - A role for prostaglandins in the suppression of cutaneous cellular immunity and tumour development in benzo(a)pyrene- but not dimethylbenz(a)anthracene-treated mice. AB - Prostaglandins have been implicated in the immune suppression associated with the development of some tumours. Application of the prostaglandin synthetase inhibitor indomethacin, to murine skin prior to treatment with the chemical carcinogens benzo(a)pyrene (BP) or 7,12 dimethylbenz(a)anthracene (DMBA), restored contact sensitivity responses to 2,4-dinitrofluorobenzene in BP- but not DMBA-treated mice. However, indomethacin failed to restore antibody responses in either group of mice. Prolonged treatment with BP or DMBA led to cutaneous tumour formation. Indomethacin was found to delay the onset and reduce the size of tumours in BP- but not DMBA-treated mice. It is proposed that prostaglandin induced suppression of cellular cutaneous immunity may play a role in BP- but not DMBA-induced cutaneous carcinogenesis. PMID- 1906387 TI - Cardiovascular responses to nifedipine in anaesthetized rats with abnormal blood gas/pH levels. AB - 1. Blood pressure and pulse rate responses to intravenously (i.v.) administered nifedipine were studied in chloralose-anaesthetized rats subjected to hypoxaemia, hyperoxaemia, alkalosis, acidosis, hypocarbia with alkalosis, or hypercarbia with acidosis. 2. Ventilation with a gas mixture of 17% O2, 28% O2, or 23% O2 with 5% CO2 at a fixed stroke volume (10 mL/kg) and rate (80 strokes/min) induced hypoxaemia, hyperoxaemia or hypercarbia, respectively. Hypocarbia was induced by ventilation with 17% O2 at 160 strokes/min. Acidosis or alkalosis was produced by intravenous infusion of 1 mol/L HCl or 1 mol/L NaHCO3, respectively, in animals ventilated with room air. 3. There were significant decreases in blood pressure and pulse rate during acidosis, and increases in pulse rate during alkalosis and hypercarbia. No marked changes in these parameters were observed under the other experimental conditions. 4. The control animals showed a dose-dependent decrease in blood pressure without marked changes in pulse rate in response to nifedipine injection. 5. Significant reductions in the hypotensive effect of nifedipine were observed in rats subjected to alkalosis, acidosis, or hypercarbia. A similar tendency was also found during hypocarbia while the responses to nifedipine during hypoxaemia and hyperoxaemia were statistically the same as those in the controls. 6. It is concluded that alterations of blood pH reduce the hypotensive effect of nifedipine, and we suggest that blood pH changes probably play a more important role than PO2 or PCO2 abnormalities in altering the cardiovascular responses to nifedipine in hypoventilated or hyperventilated rats. PMID- 1906388 TI - Relationships among LH, FSH and prolactin secretion, storage and response to secretagogue and hypothalamic GnRH content in ovariectomized pony mares administered testosterone, dihydrotestosterone, estradiol, progesterone, dexamethasone or follicular fluid. AB - Thirty-five ovariectomized pony mares were used to study the relationships among luteinizing hormone (LH), follicle stimulating hormone (FSH) and prolactin (PRL) concentrations in blood (secretion), in pituitary (storage) and in blood after secretagogue administration, as well as the content of gonadotropin releasing hormone (GnRH) in hypothalamic areas, under various conditions of steroidal and nonsteroidal treatment. Five mares each were treated daily for 21 d with vegetable shortening (controls), testosterone (T; 150 micrograms/kg of body weight, BW), dihydrotestosterone (DHT; 150 micrograms/kg BW), estradiol (E2; 35 micrograms/kg BW), progesterone (P4; 500 micrograms/kg BW), dexamethasone (DEX; 125 micrograms/kg BW) or charcoal-stripped equine follicular fluid (FF; 10 ml). Secretagogue injections (GnRH and thyrotropin releasing hormone, TRH, at 1 and 4 micrograms/kg of BW, respectively) were given one d prior to treatment and again after 15 d of treatment. Relative to controls, treatment with T, DHT and DEX reduced (P less than .05) LH secretion, storage and response to exogenous GnRH, whereas treatment with E2 increased (P less than .05) these same characteristics. Treatment with P4 reduced (P less than .05) only LH secretion. Treatment with T, DHT, E2 and DEX reduced (P less than .05) FSH secretion, whereas treatment with P4 increased (P less than .05) it and FF had no effect (P greater than .1). All treatments increased (P less than .05) FSH storage, whereas only treatment with T and DHT increased (P less than .05) the FSH response to exogenous GnRH. Other than a brief increase (P less than .05) in PRL secretion in mares treated with E2, secretion of PRL did not differ (P greater than .1) among groups. Only treatment with E2 increased (P less than .01) PRL storage, yet treatment with T or DHT (but not E2) increased (P less than .05) the PRL response to exogenous TRH. Content of GnRH in the body and pre-optic area of the hypothalamus was not affected (P greater than .1) by treatment, whereas treatment with T, E2 and DEX increased (P less than .1) GnRH content in the median eminence. For LH, secretion, storage and response to exogenous GnRH were all highly correlated (r greater than or equal to .77; P less than .01). For FSH, only storage and response to exogenous GnRH were related (r = .62; P less than .01). PRL characteristics were not significantly related to one another. Moreover, the amount of GnRH in the median eminence was not related (P greater than .1) to any LH or FSH characteristic. PMID- 1906389 TI - Bovine pituitary, kidney, uterine and mammary gland extracts contain bovine mammary epithelium growth factors that synergise with IGF-I and fetal calf serum: indication for involvement of GTP-binding proteins. AB - Bovine mammary undifferentiated epithelial cells from young female calves, cultured in three-dimensional collagen gels in serum-free medium exhibited ultrastructural organization that resembled the in vivo situation. Extracts of bovine pituitary, kidney, uterus and mammary gland, stimulated cell proliferation in a dose-dependent manner. This mitogenic activity strongly synergised with the existant growth factors (GFs) in FCS and with IGF-I, while the addition of EGF had only minor effect. No synergistic manifestation was found with cholera toxin but pertussis toxin inhibited the growth-promoting activity of all four extracts. Other experiments indicated that this mitogenic activity does not result from prolactin, growth hormone or fibroblast growth factor. The present and former results, in which synergism between IGF-I and cholera toxin was demonstrated, suggest therefore, that the mitogenesis of normal mammary epithelial cells regulated by several tissue derived growth factors, consists of at least two pathways which are distinct from those activated by EGF and IGF-I. One of these pathways indicates involvement of pertussis toxin-sensitive GTP-binding proteins, and the other, activation of cholera toxin-sensitive adenylate cyclase. PMID- 1906390 TI - Ovarian follicle populations and ovulation rates of Finnish Landrace cross ewes in different nutritional states and associated profiles of gonadotrophins, inhibin, growth hormone(GH) and insulin-like growth factor-I. AB - Effects of ewe body condition and level of feed intake on ovarian follicle populations and ovulation rates were studied in three groups of 12 to 15 Finnish Landrace cross ewes. Ewes were fed to achieve target body condition scores of either 2.0 (low, LM) or 2.5 (moderate, MM) and then fed a complete pelleted ration for three weeks before study so that they maintained liveweight. Ewes of a third group were also fed to achieve condition scores of 2.5 and then fed ad libitum (MAL). Neither ewe body condition nor level of feed intake significantly affected either the number of large follicles (greater than or equal to 4 mm diameter) or the ovulation rate. The proportion of estrogenic follicles was lower in MM than LM ewes (0.77 vs. 0.96; P less than 0.05), but there was no difference in this proportion between MAL and MM ewes. Insulin-like growth factor-I (IGF-I) concentrations in the follicular fluid were unaffected by ewe body condition or level of feed intake despite significant treatment differences in circulating concentrations. Inhibin concentrations were higher in estrogenic follicles of LM compared with MM ewes, and this difference was reflected in circulating profiles. Treatment differences in LH profiles were not associated with any difference in follicle populations or ovulation rate. There were no consistent treatment effects on FSH concentrations. It is concluded that the roles of inhibin and IGF I in the control of follicle development cannot be adequately assessed on the basis of circulating concentrations alone and that there is a need to measure intrafollicular hormone profiles and associated effects on follicle physiology. PMID- 1906391 TI - A subdermal progestin implant for long-term contraception. The Medical Letter. PMID- 1906392 TI - Immune privilege and suppression of immunogenic inflammation in the anterior chamber of the eye. AB - Immunologic privilege of the anterior chamber has been associated with the capacity to induce a unique form of deviant systemic immunity after anterior chamber (AC) immunization. However, the capacity of privilege to suppress expression of immunity in the AC has not been examined. We studied the ability of the AC to sustain immunogenic inflammation after direct antigen challenge (delayed hypersensitivity-DH) in C57BL/6 mice primed to M tuberculosis (MT) antigens. Compared to subcutaneous and subconjunctival sites where primed mice demonstrated vigorous and significant DH, the anterior chambers of these mice failed to develop signs of inflammation unless toxic doses of antigen were injected. In an attempt to promote intraocular DH, the AC's of MT-primed mice were pre-treated with subinflammatory intracameral injections of IFN-gamma, a cytokine that antagonizes TGF-beta, recruits antigen presenting cells (APC) from the blood and activates resident APC precursors. It was observed that AC injection of IFN-gamma, followed 3 days later by AC challenge with 200 ng of MT, resulted in severe intraocular inflammation only in primed (but not naive) mice. We conclude that the normal mouse AC resists DH unless its immunosuppressive microenvironment is abolished, as in these experiments by IFN-gamma. We propose that impaired expression of cell-mediated immunity is an important component of immune privilege of the AC. PMID- 1906393 TI - Identification of 12(S)-hydroxyeicosatetraenoic acid in the young rat lens. AB - Evidence is presented indicating that young rat lens has the capacity to synthesize 12(S)-hydroxyeicosatetraenoic acid (12(S)-HETE) from exogenous arachidonic acid (AA). A 9,000 xg supernatant prepared from 15 day old rat lenses, when incubated with calcium and U-[14C]-AA, generated a radiolabelled product with a retention time identical to authentic unlabelled 12-HETE in two different HPLC solvent systems. Mass spectral analysis provided evidence that the metabolite was 12-HETE while chiral studies demonstrated the exclusive presence of the 12(S) isomer. Radiolabelled 12-HETE synthesis was inhibited by preincubating the 15 day old rat lens supernatant with 0.2 Mm curcumin, a mixed cyclooxygenase/lipoxygenase inhibitor. Radiolabelled 12(S)-HETE synthetic capacity was highest in the 4 day old rat lens, the earliest time period measured, and rapidly declined with age reaching negligible levels at about 4 months. These results suggest that the young rat lens possess the biosynthetic capacity to generate radiolabelled 12(S)-HETE from U-[14]C-AA. The profile of 12 HETE synthetic activity suggests a possible regulatory function of the hydroxylated AA metabolite in the developing lens. PMID- 1906394 TI - Inhibition of lymphocyte proliferation by resident ocular cells. AB - The mechanisms by which the eye maintains an immunosuppressive environment has been the subject of recent investigations. In this report we investigated the ability of resident ocular cells from the iris, choroid, and retina to inhibit lymphocyte responses in vitro. Our results demonstrate that single cell suspensions derived from iris and choroid to inhibit alloantigen induced lymphocyte proliferation. We show that this inhibition was mediated by soluble factors which are low (less than 10,000) and intermediate (10,000-30,000) molecular weight molecules. This capacity is limited to iris and choroid and is not demonstrable in cell preparations derived from the retina. We conclude from our studies that cells derived from iris and choroid are capable of regulating immune responses and suggest that these cells (or their soluble products) may play a role in the immunosuppressive environment of the eye. PMID- 1906396 TI - Changes in the T-lymphocyte subpopulation (CD+/CD8+) in the blood of patients following kidney transplant and during the acute rejection episode. AB - A study was made of changes in the ratio of CD4+/CD8+ in patients who had received cadaverous kidneys and who were under treatment with a combination of cyclosporin A + azathioprine + cor ticosteroids. The results showed that one month after the transparent there was a significant drop (P less than 0.05) in the immunoregulation index compared with the pretransplantation values. Throughout the whole period a correlation (r = -0.65, P less than 0.05) was found between the CD4+/CD8+ ratio and serum, creatinine. In recipients with acute rejection episode no significant difference was found between the CD4+/CD8+ values before the rejection episode (7 +/- 1 days and 3 +/- 1 days) and after it was diagnosed. The introduction of monoclonal antibodies specific for determinants in T-lymphocyte transplantation. Many authors have investigated changes in the CD4+ (helper inducer) to subpopulations (1) made possible immunological monitoring following the organ CDB+ (cytotoxic suppressor) ratio following the organ transplant (2, 3, 4, 5). Some reports (6, 7) have indicated that during rejection of a transplanted kidney there is a rise in the immunoregulation index (CD4+/CD8+), while other works (8, 9) failed to confirm this. Our work presents the dynamics of changes in the CD4+/CD8+ ratio in peripheral blood of recipients of cadaverous kidney transplants, and points to changes in the immunoregulation index before and during acute rejection episodes. PMID- 1906395 TI - Multiple forms of TGF-beta: distinct promoters and differential expression. AB - There are now five known distinct isoforms of TGF-beta with 64-82% identity. Of these, only TGF-beta 1, 2 and 3 thus far have been demonstrated to be expressed in mammalian tissues; TGF-beta 4 has been described only in chicken and TGF-beta 5 only in frog. Although the biological activities of these five isoforms of TGF beta are indistinguishable in most in vitro assays their sites of synthesis and localization in vivo are often distinct. Expression of the various isoforms is differentially controlled both in vivo, as in development, and in vitro after treatment of cells with steroids, such as oestrogen or tamoxifen, or with retinoids. To investigate the basis of these observations we have cloned and characterized the promoters for the human TGF-beta 1, 2 and 3 genes. Significant differences have been found: whereas the TGF-beta 1 promoter has no TATAA box and is regulated principally by AP-1 sites, both the TGF-beta 2 and 3 promoters have TATAA boxes as well as AP-2 sites and cAMP-responsive elements. Accordingly, TGF beta 1 gene expression is induced strongly by phorbol esters whereas that of TGF beta 2 and 3 is induced by forskolin, an activator of adenylate cyclase. Expression of TGF-beta 2 and 3 is often coordinately regulated in vivo in a pattern distinct from that of TGF-beta 1. PMID- 1906397 TI - Demonstration of transient bacterobilia by foreign body implantation in feline biliary tract. AB - The biliary tract of cats is known to be free of autochthonous bacteria above the sphincter of Oddi. In this experiment we investigated whether transient bacterobilia occurs in the biliary system under normal conditions. Polyethylene tubes and human cholesterol stones were implanted surgically into the gallbladder of cats. Sham cholecystostomy was performed as control operation. These cats were euthanized at two, six, and 12 weeks, and the implants were removed, cultured, and studied by scanning electron microscopy (SEM). Cultures and SEM also were undertaken for material scraped from the mucosal surface of the biliary tract from these animals. Colonization of bacteria on the polyethylene tubes and the gallstones was found six and 12 weeks after implantation. Adherent bacterial biofilms were demonstrated on the surfaces of these implants. This experiment showed that transient bacterobilia exists in the feline biliary tract. The foreign body implants have facilitated the adhesion of planktonic bacteria in the bile onto their surfaces and have initiated the formation of adherent biofilms within which these bacteria persisted until the system was sampled. PMID- 1906398 TI - Lithotripsy versus cholecystectomy for management of gallstones. A decision analysis by Markov process. AB - Extracorporeal shock-wave lithotripsy is a new treatment method that effectively distintegrates radiolucent gallstones and is associated with a low complication rate. Using the model of a Markov process for decision analysis, survival and costs under four possible strategies to treat gallstones were compared: expectant management with cholecystectomy (EC) or lithotripsy (EL) reserved for symptomatic gallstones; prophylactic cholecystectomy (PC) or lithotripsy (PL) for all gallstones. Life expectancy for the different strategies varies by few days. Only if high annual rates of pain and complication occurred in subjects with silent gallstones would both prophylactic procedures marginally increase life expectancy. Prophylactic cholecystectomy then would be more cost-effective than prophylactic lithotripsy. Expectant strategies remain much cheaper than prophylactic management over a broad range of probability values and procedural costs. Expectant use of lithotripsy costs less than cholecystectomy. A low success rate of lithotripsy would raise the direct costs of lithotripsy above those of cholecystectomy but leave total costs of both strategies in the same order of magnitude. Lithotripsy appears to be a feasible alternative to treat symptomatic but not asymptomatic gallstones. PMID- 1906399 TI - Roles of deoxycholate and arachidonate in pathogenesis of cholesterol gallstones in obese patients during rapid loss of weight. AB - Our aim was to examine the relationship between biliary deoxycholate and arachidonate in obese patients and the relationship of deoxycholate and arachidonate to the stimulation of biliary mucous glycoprotein among obese patients predisposed to cholesterol gallstones. Thirty-four obese patients predisposed to cholesterol gallstones by a weight-reducing diet (520 kcal/day) received placebo, ursodiol (1200 mg/day), or aspirin (1300 mg/day). Duodenal bile was collected prior to beginning the diet and at four weeks. There was no correlation between deoxycholate and arachidonate among the 34 patients before beginning the diet. With placebo, deoxycholate decreased while arachidonate and glycoprotein increased. With ursodiol, deoxycholate decreased while arachidonate decreased and glycoprotein did not change. With aspirin, there was no change in deoxycholate but a decrease in arachidonate and no change in glycoprotein. Our data do not support a role for biliary deoxycholate in the regulation of biliary arachidonate. Our data do support a role for arachidonate, but not deoxycholate, in the regulation of biliary glycoprotein during the formation of cholesterol gallstones. PMID- 1906400 TI - Secretion of lipid-poor nascent human apolipoprotein apoAI, apoCIII, and apoE by cell clones expressing the corresponding genes. AB - The human apolipoprotein apoAI, apoCIII, and apoE genes were placed under the control of the mouse metallothionein 1 promoter in a bovine papilloma virus vector that also contained the human metallothionein 1A gene. Following transfection of mouse C127 cells with the expression vector, cell clones resistant to Cd2+ were selected and found to express in high abundance specific apolipoprotein genes. Individual cell clones expressing apoAI, apoCIII, or apoE genes were used further to study the isoprotein composition and the flotation properties of the corresponding nascent apolipoproteins. It was found that the lipoproteins secreted by cell clones expressing the apoAI, apoCIII, and apoE genes consisted of the proapoAI disialylated form of apoCIII (apoCIIIS2) and mainly sialylated forms of apoE. Separation of the secreted apolipoproteins by density gradient ultracentrifugation resulted in limited flotation of nascent apoAI, apoE and apoCIII in the high density lipoprotein (HDL) fraction. Similar analysis in the presence of human serum increased the flotation of apoAI, apoE, and apoCIII to 6.5-, 4.5-, and 5.5-fold, respectively, and resulted in their redistribution to various lipoprotein fractions. HDL increased the flotation of apoAI to 12-fold and very low density lipoprotein (VLDL) increased the flotation of apoCIII and apoE to 6.5- and 5.5-fold, respectively. These findings suggest that in the cell system used, the majority of nascent apoAI, apoCIII and apoE is secreted in the lipid-poor form, which then associates extracellularly with preexisting lipoproteins. PMID- 1906401 TI - Separation of human alloalbumin variants by isoelectric focusing. AB - A technique for the separation of human alloalbumin variants by means of isoelectric focusing in the presence of 8M urea and 60 mM L-serine is described. The potential usefulness of this technique in the detection and classification of genetic heterogeneity at the albumin locus is demonstrated by the differentiation of three human alloalbumin variants of European origin. PMID- 1906402 TI - On the mechanism of transcellular lipoxin formation in human platelets and granulocytes. AB - Endogenous arachidonic acid was converted to lipoxins A4, B4 and (6S)-lipoxin A4, in ionophore-A23187-stimulated mixtures of human platelets and granulocytes, while no lipoxins were formed when these cells were incubated separately. However, pure platelet suspensions transformed exogenous leukotriene A4 to lipoxins, including lipoxin A4 and (6S)-lipoxin A4, but not lipoxin B4. This compound was produced exclusively in the presence of granulocytes. A common unstable tetraene intermediate in lipoxin formation, 15-hydroxy-leukotriene A4 [5(6)-epoxy-15-hydroxy-7,9,13-trans-11-cis-eicosatetraenoic acid], was indicated by trapping experiments with methanol. Thus, identical profiles of less polar tetraene-containing derivatives were formed from leukotriene A4 in platelet suspensions, from exogenous 15-hydroxyeicosatetraenoic acid in granulocyte suspensions and from endogenous substrate in mixed platelet/granulocyte suspensions. Evidence for the involvement of 12-lipoxygenase in platelet dependent lipoxin formation was obtained. Thus, lipoxin synthesis from leukotriene A4 and 12-hydroxyeicosatetraenoic acid production from arachidonic acid by human platelets was equally inhibited by 15-hydroxyeicosatetraenoic acid with 50% inhibition obtained at 7.0 microM and 8.2 microM, respectively. In experiments with subcellular preparations from platelets, lipoxin synthesis was observed in both the particulate and soluble fraction and was paralleled by the 12-lipoxygenase activity. Furthermore, lipoxin formation from leukotriene A4 in platelet sonicates was dose-dependently inhibited by exogenous arachidonic acid. Finally, 12-lipoxygenase-deficient platelets from a patient with chronic myelogenous leukemia were totally unable to produce lipoxins from exogenous or granulocyte-derived leukotriene A4. It is concluded that the transcellular lipoxin synthesis is dependent on the platelet 12-lipoxygenase and proceeds via the unstable intermediate, 15-hydroxy-leukotriene A4. This tetraene epoxide is transformed to lipoxin B4 by a granulocyte epoxide hydrolase activity or to lipoxin A4 and lipoxins A4/B4 isomers by enzymatic or nonenzymatic hydrolysis. PMID- 1906403 TI - Molecular analysis of a human interferon-inducible gene family. AB - Three functional members of the 1-8 gene family have been isolated on a single human genomic DNA fragment of less than 18 kb. The 1-8U and 1-8D genes are extremely similar; each is contained within a less than 2-kb fragment, has in its 5'flanking region two adjacent 14-base-pair sequences showing high similarity to interferon-stimulable response elements (ISREs) and has two highly related exons. The third gene (9-27) has a similar overall structure, shows substantial similarity to the 1-8s but has only one ISRE which is 3' of two CCAAT boxes not present in the 1-8U and D genes. The cDNA corresponding to the three genes share 120 nucleotides of identical sequence and show greater than 90% identity over 70% of the coding sequence. For the 1-8U and D genes the high similarity extends into the 5' non-coding and flanking regions. The open reading frames encode polypeptides that are likely to be of very similar structure. Antiserum to a conserved peptide detects a polypeptide(s) of about 14 kDa on PAGE which separates into three components on isoelectric focussing. The 9-27 and 1-8U genes are highly interferon-inducible the 1-8D gene is much less so. These differences are mimicked by the activities of the corresponding ISREs placed 5' of a marker gene in expression constructs. They presumably reflect differences in the interaction of the ISREs with the various interferon-inducible and constitutive factors that govern the interferon response. PMID- 1906404 TI - Hydroperoxides of alpha-ketols. Novel products of the plant lipoxygenase pathway. AB - Metabolism of [1-14C]linolenic acid, 13-hydroperoxy-8(Z),11(E),15(Z)-[1 14C]octadecatrienoic acid (13-HPOT) and 9-hydroperoxy-10(E),12(Z),15(Z)-[1 14C]octadecatrienoic acid (9-HPOT) was studied by enzyme preparations from flax, wheat and corn seeds, containing two enzymes of fatty acid metabolism, namely, lipoxygenase and hydroperoxide dehydrase. Along with the previously known products of the hydroperoxide dehydrase pathway, the radiolabel was incorporated into some more polar metabolites. These polar products 1 and 4, formed from 13 HPOT and 9-HPOT, respectively, were purified by reversed-phase and normal-phase HPLC, and investigated by ultraviolet spectroscopy, chemical-ionization and electron-impact mass spectrometry, and 1H-NMR. The data obtained suggest that metabolites 1 and 4 are 9-hydroperoxy-12-oxo-13-hydroxy-10(E),15(Z) octadecadienoic acid and 9-hydroxy-10-oxo-13-hydroperoxy-11(E),15(Z) octadecadienoic acid, respectively. 12-oxo-13-hydroxy-9(Z),15(Z)-[1 14C]octadecadienoic acid (12,13-alpha-ketol) and 9-hydroxy-10-oxo-12(Z),15(Z)-[1 14C]octadecadienoic acid (9,10-alpha-keto) are the direct precursors of metabolites 1 and 4, respectively. Metabolites 1 and 4 are formed from the corresponding HPOT precursors in two stages; (a) conversion of hydroperoxide into the alpha-ketol by hydroperoxide dehydrase and (b) the lipoxygenase oxidation of the alpha-ketol. Different lipoxygenases were found to oxidize alpha-ketols. Oxidation of the 3(Z)-buten-1-onyl moiety of alpha-ketols presents an unusual and previously unknown type of lipoxygenase reaction. PMID- 1906405 TI - The male reproductive organs in experimental Chagas' disease. I. Morphometric study of the vas deferens in the acute phase of the disease. AB - Amastigote forms of Trypanosoma cruzi (Bolivia strain) were detected in the sex organs of male mice 15 days after inoculation. The presence of the parasite close to the lumen of the seminiferous tubules and mixed with spermatozoa in the lumen of the epididymal duct suggests the possibility of transmission of Chagas' disease through coitus. Morphological analysis of the vas deferens revealed structural alterations compatible with the early form of chagasic esophagopathy. PMID- 1906406 TI - Induction of preovulatory luteinizing hormone surge and prevention of ovarian hyperstimulation syndrome by gonadotropin-releasing hormone agonist. AB - OBJECTIVE: To use gonadotropin-releasing hormone agonist (GnRH-a) instead of human chorionic gonadotropin (hCG) to induce oocyte maturation for in vitro fertilization (IVF). DESIGN: Pituitary and ovarian responses to GnRH-a and the outcome of IVF were studied prospectively. Data from patients injected with hCG were analyzed retrospectively. SETTING: Program of IVF at the Rambam (Governmental) Hospital, Haifa, Israel. PATIENTS AND INTERVENTIONS: One or two doses of buserelin acetate 250 to 500 micrograms were administered to six patients with moderate response (Estradiol [E2], 1,494 +/- 422 [+/- SD] pg/mL) and 8 patients with exaggerated response (E2, 7,673 +/- 3,028 pg/mL) to gonadotropin stimulation. Progesterone (P) and E2 were administered for luteal support. MAIN OUTCOME MEASURES: Gonadotropin-releasing hormone agonist effectively triggered luteinizing hormone (LH)/follicle-stimulating hormone (FSH) surge. Mature oocytes were recovered in all patients. Luteal E2 and P were lower than in patients injected with hCG. No signs of ovarian hyperstimulation syndrome were observed. RESULTS: Serum LH and FSH rose over 4 and 12 hours, respectively, and were significantly (P less than 0.05) elevated for 24 hours. Of all mature oocytes, 67% fertilized and 82% cleaved. Four pregnancies were obtained. CONCLUSIONS: A bolus of GnRH-a is able to trigger an adequate midcycle LH/FSH surge, resulting in oocyte maturation and pregnancy. Our preliminary results also suggest that it allows a more accurate control of ovarian steroid levels during the luteal phase and may prevent the clinical manifestation of ovarian hyperstimulation syndrome. PMID- 1906407 TI - Norplant implants: the mechanism of contraceptive action. AB - OBJECTIVE: To determine if fertilization occurs unnoticed among Norplant users who are ovulatory. DESIGN: Serial blood samples were obtained during 1 month from sexually active Norplant users experiencing regular menstrual bleeding patterns and a control group of noncontracepting women trying to conceive. The sequential blood samples were assayed for the presence of human chorionic gonadotropin (hCG). SETTING: All samples were obtained from women receiving contraceptive service and health care at the Center for Research and Services in Human Reproduction and Contraception, Santo Domingo, The Dominican Republic. Assays for hCG were performed at the Department of Biomedical Sciences, University of Tampere, Finland. PATIENTS, PARTICIPANTS: A total of 32 women using Norplant implants were enrolled in the treatment group, and 20 women of proven fertility who were attempting to conceive served as a control group. INTERVENTIONS: Duration of Norplant use was as follows: 4 in the 2nd year of use, 13 in the 3rd year, 11 in the 4th year, 3 in the 5th year, and 1 in the 7th year. MAIN OUTCOME MEASURE: The determination of pregnancy was based on the presence of hCG in the luteal phase, using a sensitive and specific immunoenzymatic assay that can detect dimeric hCG as early as 7 days after ovulation. RESULTS: Nine pregnancies were detected. All were in the control group trying to conceive. Six of these advanced to clinical pregnancies, and three did not proceed beyond the next expected menses. None of the Norplant users had evidence of hCG production, whether the observed cycles were anovulatory or ovulatory. The probability of finding no pregnancies in the ovulatory months at risk among Norplant users is between 1 in 50 and 1 in 150,000. The null hypothesis that Norplant users conceive at a natural rate can be rejected at the 0.05 level. CONCLUSION: Interruption of early pregnancy (menstrual abortion) does not play a role in the mechanism of action of Norplant contraceptive implants. PMID- 1906408 TI - Follicular size at the time of human chorionic gonadotropin administration predicts ovulation outcome in human menopausal gonadotropin-stimulated cycles. AB - OBJECTIVE: The objectives of this study were: (1) to correlate follicle size by transvaginal sonography with ovulation outcome in cycles of controlled ovarian hyperstimulation with human menopausal gonadotropins; (2) to determine if follicular size on the day of human chorionic gonadotropin (hCG) administration predicts the incidence of ovulation; and, if so, (3) to derive a mathematical model that predicts the number of expected ovulations in any given cycle of controlled ovarian hyperstimulation. DESIGN: A retrospective analysis. PARTICIPANTS: Forty-nine consecutive patients undergoing 122 cycles of controlled ovarian hyperstimulation were studied in a tertiary care setting. MAIN OUTCOME MEASURES: Follicular size and evidence of ovulation were determined sonographically. The main outcome measure was the rate of ovulation per follicle size. RESULTS: The percentages of follicles measuring less than or equal to 14 mm, 15 to 16 mm, 17 to 18 mm, 19 to 20 mm, and greater than 20 mm on the day of hCG administration that subsequently ovulated were 0.5%, 37.4%, 72.5%, 81.2%, and 95.5%, respectively. CONCLUSIONS: (1) Follicular size on the day of hCG administration correlates with the incidence of ovulation. (2) The expected number of ovulations in any given controlled ovarian hyperstimulation cycle can be predicted with 95% confidence using the accompanying equation. PMID- 1906409 TI - Immaturity and aneuploidy in human oocytes after different stimulation protocols. AB - OBJECTIVE: To study immaturity and aneuploidy in human oocytes after two different stimulation protocols. DESIGN: Retrospective. SETTING: Outpatient IVF clinic/laboratory. PATIENTS: One hundred forty-three patients of whom 65 were stimulated with clomiphene citrate (CC)/human menopausal gonadotropin (hMG) and 78 were stimulated with gonadotropin-releasing hormone agonist (GnRH-a)/hMG. Only patients with at least one oocyte unfertilized were included in this study. RESULTS: Stimulation with GnRH-a/hMG, as compared with CC/hMG stimulation, resulted in larger numbers of oocytes (P less than 0.00001), a higher fertilization rate (P less than 0.02), and oocyte retrieval at a later average cycle day (P less than 0.000005). Cytogenetic findings of immaturity were observed in 33.9% of unfertilized oocytes after CC/hMG stimulation, compared with only 17.8% after GnRH-a/hMG stimulation (P less than 0.0005). Aneuploidy findings were the same for both groups. CONCLUSION: In GnRH-a/hMG stimulation, oocytes approach the normal day of ovulation more closely. This may allow for better oocyte maturation and higher fertilization and pregnancy rates. PMID- 1906410 TI - Subcutaneous gonadotropin therapy in male patients with hypogonadotropic hypogonadism. AB - OBJECTIVE: The response to subcutaneous (SC) gonadotropin replacement therapy, using human chorionic gonadotropin (hCG) and human menopausal gonadotropin (hMG) or hCG alone, was evaluated in male hypothalamic hypogonadism. DESIGN: Sixteen patients with hypothalamic hypogonadism were treated with gonadotropins for induction of puberty and normalization of spermatogenesis. The results were analyzed retrospectively. SETTING: The study was carried out in a clinical endocrinology department providing tertiary care and in private practices of endocrinology. PATIENTS: Eight patients with idiopathic hypogonadotropic hypogonadism and eight patients with Kallmann's syndrome in prepubertal or early pubertal stages. INTERVENTIONS: Human chorionic gonadotropin and hMG were administered SC in individual dosages. MAIN OUTCOME MEASURES: Increase of serum testosterone (T), testicular volume, semen volume, and sperm count were evaluated. RESULTS: Normalization of serum T and complete sexual maturation was achieved in all patients. Spermatogenesis was induced in all but two patients. Seven patients showed normal findings in semen volume and sperm count, and two patients had semen quality close to normal. In five patients sperm count remained less than 10 x 10(6)/mL. CONCLUSIONS: The results obtained by SC gonadotropin replacement prove this mode of administration to be effective in stimulating steroidogenesis and spermatogenesis in hypogonadotropic males. PMID- 1906411 TI - GnRH agonists and ovarian hyperstimulation. PMID- 1906412 TI - Initiation of spermatogenesis and successful in vitro fertilization in an infertile male with panhypopituitarism; superiority of pulsatile LH-RH over gonadotropins? A case report. AB - This case report describes an infertile male patient with panhypopituitarism, presumably caused by traumatic breech delivery. Previous hMG/hCG treatment had failed to induce spermatogenesis. Initiation of the production of motile and morphological normal sperm, despite persisting significant oligozoospermia was established with s.c. pulsatile LH-RH treatment. Spermatogenesis could be maintained with i.m. hCG injections bi-weekly. Later, fruitful in vitro fertilization (IVF) resulted in the birth of a healthy daughter. PMID- 1906414 TI - A new approach to performing endoscopic sphincterotomy in the setting of a juxtapapillary duodenal diverticulum. PMID- 1906413 TI - [Cost-effectiveness of preventive treatment with misoprostol in non-steroidal anti-inflammatory agents related gastric ulcers]. AB - The prophylactic use of misoprostol for patients with osteoarthritis and abdominal pain receiving non steroid anti-inflammatory drugs has been shown to reduce the incidence of gastric ulcers by a factor of 15. We studied the direct medical expenses related to this treatment, as compared to no prevention. Considering only ulcers over 3 mm, a daily dose of 400 micrograms/day, with a compliance rate of 60 percent and a 40 percent rate of silent ulcers, prevention induced an extra cost of 131 FF per payor for 3 months. For the French illness fund, the extra cost was 54 FF while patient copayment was 77 FF. Prevention was calculated to prevent 84 gastric ulcers per 1,000 cases. Results are very dependent on the variability of clinical results, the price of the drug, but less on the cost of the ambulatory treatment of ulcer and on the rate of hospitalization. It was not possible to extrapolate results beyond 3 months. This model did not take into account indirect costs such as loss of work hours, as well as qualitative benefits of prevention such as better compliance to NSAIDs. These factors would improve the cost-effectiveness of treatment. Prevention by misoprostol should be compared with other antiulcer drugs which have not yet proven their preventive efficacy. PMID- 1906415 TI - Subcutaneous emphysema following PEG. PMID- 1906416 TI - DNA repair and the evolution of transformation in Bacillus subtilis. III. Sex with damaged DNA. AB - Natural genetic transformation in the bacterium Bacillus subtilis provides an experimental system for studying the evolutionary function of sexual recombination. The repair hypothesis proposes that during transformation the exogenous DNA taken up by cells is used as template for recombinational repair of damages in the recipient cell's genome. Earlier results demonstrated that the population density of transformed cells (i.e., sexual cells) increases, relative to nontransformed cells (primarily asexual cells), with increasing dosage of ultraviolet irradiation, provided that the cells are transformed with undamaged homologous DNA after they have become damaged. In nature, however, donor DNA for transformation is likely to come from cells that are as damaged as the recipient cells. In order to better simulate the effects of transformation in natural populations we conducted similar experiments as those just described using damaged donor DNA. We document in this report that transformants continue to increase in relative density even if they are transformed with damaged donor DNA. These results suggest that sites of transformation are often damaged sites in the recipient cell's genome. PMID- 1906417 TI - The independent distorting ability of the Enhancer of Segregation Distortion, E(SD), in Drosophila melanogaster. AB - Segregation distortion is a meiotic drive system, discovered in wild populations, in which males heterozygous for an SD chromosome and a sensitive SD+ homolog transmit the SD chromosome almost exclusively. SD represents a complex of three closely linked loci in the centromeric region of chromosome 2: Sd, the Segregation distorter gene; E(SD), the Enhancer of Segregation Distortion, required for full expression of drive; and Rsp, the target for the action of Sd, existing in a continuum of states classifiable into sensitive (Rsps) and insensitive (Rspi). In an SD/SD+ male which is Sd E(SD) Rspi/Sd+ E(SD)+ Rsps, the Sd and E(SD) elements act jointly to induce the dysfunction of those spermatids receiving the Rsps chromosome. By manipulating the number of copies and the position of the Enhancer region, I demonstrated that: (1) E(SD), whether in its normal position or translocated to the Y chromosome, is able to enhance the degree of Sd-caused distortion in a dosage-dependent manner; (2) even in the absence of Sd, the E(SD) allele in two doses can cause significant distortion, in Sd+ or Df(Sd)-bearing genotypes; (3) quantitative differences among Enhancers of different sources suggest allelic variation at E(SD), which could account at least in part for differences among wild SD chromosomes in strength of distortion; (4) E(SD)/E(SD)-mediated distortion, like that of Sd, is directed at the Rsp target, whether Rsp is on the second or the Y chromosome; (5) E(SD), like Sd, is suppressed by an unlinked dominant suppressor of SD action. These results show that E(SD) is independently capable of acting on Rsp and is not a simple modifier of the action of Sd. E(SD) provides an example of a trans-acting gene embedded in heterochromatin that can interact with another heterochromatic gene, Rsp, as well as parallel the effect of a euchromatic gene, Sd. PMID- 1906418 TI - Two modes of balancing selection in Drosophila melanogaster: overcompensation and overdominance. AB - Overdominance is often invoked to account for the extensive polymorphisms found in natural populations of organisms; overcompensation, however, may be equally or more important. Overcompensation occurs when limiting resources are better exploited by a genetically mixed than by a uniform population, and is often causally related to frequency-dependent selection. We have designed experiments to test whether overcompensation occurs in Drosophila melanogaster, using the Sod locus as a marker. Tests are made at each of two densities and two temperatures for cultures with desired genetic compositions. Both temperature and density have statistically significant effects on the per-female productivity of the cultures. More important, there are strong effects due to overcompensation. Cultures that are more polymorphic are also more productive than less polymorphic ones even when the level of individual heterozygosity is the same in all. There is also overdominance for the Sod locus: the heterozygotes are more productive than either homozygote at every temperature and density, and the differences are statistically significant in several cases. These results corroborate previous studies showing that overdominance may contribute to the maintenance of the Sod polymorphisms. Moreover, our results indicate that the significance of overcompensation as a mechanism to account for polymorphism in natural populations deserves further investigation. PMID- 1906419 TI - Isolation of Mn-SOD and low active Fe-SOD from Methylomonas J; consisting of identical proteins. AB - Cultures of Methylomonas J, an aerobic methylotrophic bacterium, were grown both in Mn-rich and Fe-rich media. Crude extracts of the cultures from the Mn-rich and Fe-rich medium showed a specific activity of 12.2 and 0.6 units/mg by a cytochrome c-xanthine oxidase method and 19.4 and 1.3 units/mg by an ESR method, respectively. We isolated Mn-SOD and Fe-SOD from the bacteria grown in the Mn rich and Fe-rich mediums, respectively. Specific activity and metal contents of the Mn-enzyme were 2,250 units/mg/g-atom Mn and Mn = 0.98 and Fe = 0.12 (g atoms/mol dimer), while those of the Fe-enzyme were 61 units/mg/g-atom Fe and Mn = 0.02 and Fe = 1.08. No difference of physicochemical properties of the Fe- and Mn-enzymes were detected. Furthermore, enzyme activity was restored by dialysis of an apoprotein obtained from the Fe-enzyme with either manganese sulfate or ferrous ammonium sulfate. PMID- 1906420 TI - On the mechanism of action of H2O2 in the cellular stress. AB - We propose a hypothesis according to which the reactive and reduced species of oxygen could be the intracellular inducers of the stress (or "heat-shock") response. This hypothesis is based on the following observations on Drosophila cells: a) the return to normoxia after 24 h anaerobiosis is sufficient to induce the synthesis of the "heat shock" proteins without elevation of temperature together with a rapid increase of O2 consumption; b) hydrogen peroxide introduced in the culture medium induces the early transcriptional activation of the "heat shock" genes (maximal after 5 minutes); c) hydrogen peroxide added to cellular extracts in vitro (thus acting as an intracellular metabolite) activates instantaneously the binding capacity of a "heat shock" factor to a DNA "heat shock" regulatory element. Thus, hydrogen peroxide, and possibly other reactive reduced species of oxygen, could trigger the onset of the stress (or "heat shock") response. PMID- 1906421 TI - [Problems with long-term therapy]. PMID- 1906422 TI - [Traveling with children--what should be considered?]. AB - A holiday shared by parents and children can be a delightful experience, provided the parents give due attention to the needs of their children dictated by age, mind, psychology and physique. If this is done, the children are more likely to look back on the holiday with pleasure rather than finding it a harrowing experience best forgotten. In particular in the case of very young and pre-school children, long journeys with young children are not a good idea, and may be associated with numerous disadvantages and health risks. The psychological and physical situation in to tropical and subtropical regions are discussed with respect to the planning of a suitable holiday. PMID- 1906423 TI - Hepatocellular ballooning after liver transplantation: a light and electronmicroscopic study with clinicopathological correlation. AB - The histopathological features of orthotopic liver grafts were studied in 107 serial specimens from 25 patients, to assess the prevalence, possible pathogenesis and prognostic implications of hepatocellular ballooning. Ballooned hepatocytes were found in 46 (54%) of 85 biopsies taken five or more days after transplantation from 16 patients. They were not found in any of the protocol biopsies taken at the time of the operation. Ballooning usually appeared in the second week after transplantation, and in most patients persisted to the time of the latest biopsy studied. The affected cells were always found in acinar zone 3, and sometimes also in other zones. Forty-four of the 46 biopsies with ballooning were taken during a period of clinical and biochemical cholestasis. In 13 of the 16 patients the degree of ballooning paralleled the severity of the cholestasis. Electronmicroscopy of affected hepatocytes showed conspicuous dilatation of the cisternae of the rough endoplasmic reticulum rather than the classical features of cholestasis. It was therefore concluded that ballooning was associated with but not directly caused by bile retention. There was no obvious association between ballooning and cellular rejection, sepsis, immunosuppressive therapy or parenteral nutrition. The most severe early ballooning was associated with serum transaminase levels over 1000 IU/l within 48 h of transplantation, suggesting that ischaemia was one of the pathogenetic factors. Hepatocellular ballooning did not in itself appear to have sinister short-term prognostic implications. PMID- 1906424 TI - Lymphocytes bearing the gamma delta T-cell receptor in normal human intestine and celiac disease. AB - Monoclonal antibodies to T-cell receptors were used to investigate the prevalence of the two distinct T-cell subpopulations (TCR alpha beta+ and TCR gamma delta+ cells) in the intestinal mucosa of children with celiac disease (gluten-sensitive enteropathy) as compared with normal intestinal mucosa. TCR gamma delta+ cells were rarely identified in the epithelium of human fetal or normal postnatal intestine and few were present in the lamina propria, whereas the number of distribution of TCR alpha beta+ cells closely resembled that of CD3+ cells. Compared with normal intestine, a significant increase in the number of CD3+, CD8+, TCR alpha beta+, and TCR gamma delta+ intraepithelial lymphocytes was present in celiac disease. Although the mucosal TCR gamma delta+ cells were less numerous than TCR alpha beta+ cells in celiac disease, there was a marked increase in the number of TCR gamma delta+ cells as compared with controls. The ligand recognized by the gamma delta T-cell receptor and the function of these cells have not been determined; however, these findings suggest a possible role for TCR gamma delta+ lymphocytes in mucosal immune responses and tissue injury as seen in celiac disease. PMID- 1906425 TI - Serum beta 2-microglobulin levels in asymptomatic HIV-1-infected subjects during long-term zidovudine treatment. AB - beta 2-microglobulin levels were determined in the serum of 18 initially asymptomatic HIV-1 p24 antigenaemic subjects who were treated with zidovudine (+/ acyclovir) and who were followed for 2 1/2 years. The median serum beta 2 microglobulin level at week 0 was 2.5 mg/l and decreased to 2.3 mg/l after 12 weeks of treatment (p = 0.001). A correlation was found between individual changes in serum beta 2-microglobulin levels and individual changes in serum p24 antigen levels during the first 48 weeks of treatment (p less than 0.05). Six out of 18 subjects progressed to AIDS after 60-126 weeks of treatment. In this group during a period of more than one year before disease progression median serum beta 2-microglobulin levels increased from 2.5 mg/l to 3.3 mg/l (p = 0.03) and median CD4+ cell counts decreased from 0.3 x 10(9)/l to 0.08 x 10(9)/l (p = 0.03), while in that period the pattern of serum p24 antigen levels was inconsistent. Although the variability in serum beta 2-microglobulin levels appeared to make this marker unsuitable for management decisions in individuals, a decline in beta 2-microglobulin levels was found to parallel a decline in p24 antigen levels during the early phase of zidovudine treatment. Moreover, after prolonged treatment, rising beta 2-microglobulin levels--in contrast to p24 antigen levels--were shown to have predictive value for disease progression. PMID- 1906426 TI - New genes in the class II region of the human major histocompatibility complex. AB - A detailed map of the class II region of the human major histocompatibility complex has been constructed by pulsed-field gel electrophoresis. This map revealed clusters of sites for enzymes that cut preferentially in unmethylated CpG-rich DNA often found at the 5' ends of genes. Three of these clusters have been cloned by cosmid walking and chromosome jumping. Analysis of the clones encompassing these regions through the use of zoo blots, Northern blots, and cDNA libraries resulted in the discovery of four novel genes. The D6S111E and D6S112E genes are centromeric to the HLA-DPB2 gene, while D6S113E and D6S114E are between HLA-DNA and HLA-DOB. Preliminary characterization of the new genes indicates that they are unrelated to the class II genes themselves, although D6S114E expression, like class II expression, is inducible with interferon. In addition, the HLA-DNA gene has been accurately positioned and oriented for the first time. PMID- 1906427 TI - Treatment with rIFN-gamma has no effect on cardiac allograft rejection. AB - The effect of recombinant rat interferon-gamma (rRIFN-gamma) on allograft rejection was studied in two rat heart transplantation models. Recipients were treated with rRIFN-gamma by intraperitoneal or intravenous injection, either by bolus or continuous infusion. Treatment was started after transplantation and continued during a period ranging from 4 to 10 days; dosages varied from 2.5 x 10(2) U/kg/day to 3 x 10(6) U/kg/day. Controls were infused with PBS. Treatment with rRIFN-gamma had no effect on allograft survival, irrespective of the route of administration, the dosage used or the duration of treatment. Higher dosages of rRIFN-gamma induced serious morbidity and mortality. In conclusion, systemic treatment of cardiac allograft recipients with rRIFN-gamma has no effect on graft rejection and is associated with serious toxicity and mortality when high dosages are used. PMID- 1906428 TI - Protective immunity to Schistosoma mansoni in mice is dependent on antibody and complement but not on radiosensitive leukocytes. AB - The role of complement in the control of the Schistosoma mansoni infection in mice was investigated in vivo. The number of schistosomula recovered from the lung 5 days post-infection was used as a parasitological criterion of immunity. A significant difference in worm burden was observed between normal and immune mice. In contrast, when cobra venom factor (CVF) was injected into normal or immune mice 3 h before challenge, a significant increase in worm burden was noticed compared to untreated mice. We also investigated the protective mechanisms in mice that had been exposed to 650 rads of 60Co gamma radiation before challenge infection. Our results show that gamma-irradiated immune mice, depleted of more than 90% of their circulating or tissue leukocytes, are still able to destroy most of the parasites of a challenge infection with cercariae, suggesting that the radiosensitive leukocytes are not essential in the effector mechanisms of this protective immunity to S. mansoni. These results provide evidence of a role for the complement system, in association with radioresistant effector cells, in protective immunity occurring in the first hours after infection with S. mansoni. PMID- 1906429 TI - Physiological dead space & arterial to end-tidal CO2 difference under controlled normocapnic ventilation in young anaesthetised subjects. AB - Physiological dead space and its components were determined in 27 young, otherwise healthy anaesthetised individuals before start of surgery. A squarewave inspiratory flow pattern and an end inspiratory pause (25 and 10% of cycle time respectively) were used at a respiratory rate of around 16 bpm with minute ventilation adjusted to maintain normocapnia. The physiological dead space was found to be 2.23 ml/kg with anatomical dead space forming 110.66 +/- 27.55 ml out of 125.55 +/- 27.06 ml. While VD alv was positively correlated to pause pressure, VD ant was correlated to age, weight, and body surface area. Mean arterial end tidal carbon dioxide difference was quite low (0.24 +/- 0.44 kPa). PMID- 1906430 TI - Tumoricidal activity and cytokine secretion by tumor-infiltrating macrophages. AB - Murine macrophages from different anatomical sites were compared for their ability to become tumoricidal and to secrete interleukin-1 (IL-1) and tumor necrosis factor (TNF) following stimulation in vitro by several biological response modifiers (BRM). Peritoneal macrophages (PM), alveolar macrophages (AM), and tumor-infiltrating-macrophages (TIM), isolated from B16F10 melanoma colonies in the lung, were incubated overnight with BRM [recombinant murine interferon gamma (rMulFN-gamma), lipopolysaccharide (LPS), muramyl dipeptide (MDP)], either alone or in combination. PM exhibited an increased cytotoxic response following incubation with LPS or rMuIFN-gamma but not with MDP. Both AM and TIM were induced to become tumoricidal following incubation with rMuIFN-gamma plus LPS or rMuIFN-gamma plus MDP but not after stimulation with any BRM alone; the level of cytotoxicity obtained with TIM incubated with rMuIFN-gamma plus LPS was slightly lower than that observed with PM or AM, while with rMuIFN-gamma plus MDP both AM and TIM had lower cytotoxicity than PM. Secretion of IL-I and TNF was observed in PM stimulated with LPS or MDP but not with rMuIFN-gamma. Likewise, secretion of IL-I by AM or TIM was also induced with LPS, although less than that obtained with PM. AM stimulated with LPS secreted larger amounts of TNF than PM while TIM secreted very low amounts of TNF. However, this result may be a consequence of the enzymatic isolation procedure used to obtain TIM since TNF secretion was also impaired in LPS-stimulated normal lung macrophages isolated by a similar enzymatic procedure, or enzyme-treated PM. Our results suggest that TIM obtained from lung metastases share certain functional characteristics with normal AM and respond to BRM in like manner with respect to induction of tumoricidal activity and cytokine secretion. PMID- 1906431 TI - HLA-class-I and -class-II expression on renal tumor xenografts and the relation to sensitivity for alpha-IFN, gamma-IFN and TNF. AB - In this study we evaluated the usefulness of the histocompatibility leucocyte antigen (HLA) class-I and class-II expression on renal-cell carcinoma (RCC) xenografts as predictive markers for response to cytokine therapy. Eight different RCC xenografts growing in BALBC nu/nu mice were treated with 0.5 or 5.0 ng/g recombinant human alpha- or gamma-interferon (IFN), or 500 ng/g recombinant human tumor necrosis factor (TNF). Modulation of HLA class-I, -II expression was evaluated immunohistochemically using the monoclonal antibodies (MAbs) W6.32 and B8.11.2 and at the mRNA level using the plasmids pDP001 and DR alpha 120. HLA class-I expression in all lines was upregulated by alpha- and gamma-IFN and was highest in the high-IFN-dose-treated tumors. TNF also stimulated HLA-class-I expression and up-regulated class-I expression still further when combined with IFN. Highest up-regulation of HLA-class-I in all tumors was measured in the alpha IFN-5.0/TNF-500-ng/g-treated mice, although this was not necessarily the treatment regimen resulting in the most pronounced effect on tumor growth. Hence, maximum upregulation of class-I antigens at a given regimen was not always indicative for the highest achievable anti-tumor effect. HLA-class-II expression which was present on only 3 of the untreated tumors was up-regulated by both alpha and gamma-IFN. TNF itself did not up-regulate class-II expression but enhanced the class-II expression on the alpha-IFN-treated tumors but not on the gamma-IFN-treated tumors. Irrespective of the basic expression level, inducibility of both HLA-class-I and -class-II antigens appear to be correlated to the direct effects on growth of renal-tumor xenografts towards alpha-IFN, gamma-IFN and TNF. Modulation of HLA antigens was studied in the nude mouse, hence T-cell-mediated effector mechanisms cannot explain the good correlation between inducibility and response. Nonetheless, our studies indicate that the extent of modulation of HLA-class-I and -II can serve as predictive marker for response to cytokine therapy, which may serve as a valuable criterion for inclusion of patients in cytokine treatment regimens. PMID- 1906432 TI - Randomized comparison of flecainide and cibenzoline in the conversion of atrial fibrillation. AB - The efficacy of oral cibenzoline (260 mg/day and 320 mg/day) and flecainide (200 mg/day and 300 mg/day) in the conversion of chronic atrial fibrillation to sinus rhythm were compared in 31 patients in a randomized order. If sinus rhythm was not restored on the 5th day of oral treatment with either cibenzoline or flecainide (phase of initial treatment) patients were switched to a second phase of treatment with the drug not given in the first phase after a washout phase of 3 days. Sinus rhythm was restored in 7/28 treatment trials with cibenzoline and in 7/23 treatment trials with flecainide (not significant). Trough levels of cibenzoline and flecainide in the plasma were not significantly different between patients in whom sinus rhythm was restored and patients with persisting atrial fibrillation. In patients successfully converted to sinus rhythm, long-term treatment was instituted with flecainide (n = 6) or cibenzoline (n = 6). Atrial fibrillation developed in 2 patients in each group of patients within 3 months. In all other patients, sinus rhythm was maintained during the follow-up period of 12 months. Non-cardiac side effects were observed in 2 patients during treatment with cibenzoline and flecainide respectively. With flecainide, one patient developed sinus arrest up to 5.6 seconds. PMID- 1906433 TI - In vitro deposition and clinical efficacy of two sodium cromoglycate inhalation powders. AB - In this study, the in vitro deposition as well as the clinical efficacy of two dry powder inhalation preparations containing 20 mg of disodium cromoglycate were evaluated. The preparations were Blacil and Lomudal administered either with I.S.F. or Spinmatic powder inhalers, respectively. The in vitro inhalation study was performed using the cascade impacted method. During the in vitro test, similar fractions of the drug doses were retained in both inhalation devices. A remarkably larger proportion of the pelletized drug powder from the Lomudal preparation was deposited in the imitated upper airway than from the Blacil preparation consisting of the mixture of micronized disodium cromoglycate particles and lactose as a carrier. On the other hand, a larger fraction of the drug dose was deposited in the imitated lung area after the administration of the Blacil preparation than from Lomudal. The clinical study was performed as an exercise test in sixteen asthmatic patients. The preparations tested were statistically equally effective. The decrease in all the values of the pulmonary function parameters (PEF, FEV1) was, however, smaller after the administration of disodium cromoglycate from Blacil than from Lomudal preparation. According to the results of this study, the cascade impaction test seems to be valuable for predicting the efficacy of inhalation powders. PMID- 1906434 TI - A comparison of metoprolol OROS with antenolol in the treatment of effort angina pectoris: a randomized double-blind study. AB - The antianginal efficacy of metoprolol OROS has been investigated in comparison with that of atenolol in a multicenter double-blind cross-over trial carried out in patients with stable effort angina. OROS (ORally OSmotic) is a new semi permeable delivery system with very slow osmotic release of the active drug, which is maintained at virtually constant plasma levels throughout the 24 hours. At the end of a 2-week run-in period, 53 patients with chronic coronary artery disease and documented ischemia during bicycleergometric exercise test were given, on double-blind condition, metoprolol OROS 21/285 and atenolol 100 mg in random order for 4 weeks each. On the last day of each cross-over period, patients underwent a bicycleergometric exercise test 24 hours after the last drug intake. The mean number of anginal attacks (2.54 during the 2-week run-in period) decreased under both metoprolol OROS (1.29 and 1.13 after 2 and 4 weeks of treatment, respectively) and atenolol (1.29 and 0.73 after 2 and 4 weeks of treatment, respectively), with no difference between the two beta-blockers. The same behaviour was observed as regards the nitroglycerin tablets consumption. The exercise test variables (i.e. duration of exercise, maximum workload and peak exercise values of systolic and diastolic blood pressure, heart rate and ST segment depression) did not differ between the two treatments and did not show a time-effect. The percentage of patients reporting adverse effects was low with both treatments. Two patients were withdrawn from the study during atenolol (gastralgia and heartburn, respectively), and one during metoprolol OROS (gastralgia).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1906435 TI - Effect of the novel triazinium zwitterion 1-methyl-3-phenyl-1,2,4-triazinium-5 olate on immunological responses and experimental brucellosis in mice. AB - The immunopharmacology of a novel triazinium zwitterion, designated JR-6, was studied in mice. Experiments show dose-response inhibition of antibody and delayed-type hypersensitivity (DTH) responses to sheep red blood cell antigens. Suppression of DTH was confirmed using trinitrochlorobenzene as a contact sensitizing antigen. Using a model of experimental brucellosis in mice, it was found that JR-6 caused suppression of specific antibody and DTH reaction, as well as spleen weight, but a statistically significant increase in viable counts of Brucella abortus was not observed. Extensive short-term toxicology studies showed reduction in lymphocyte and neutrophil counts, and slow weight gain of treated mice. However, organ histology, liver function tests and biochemical profiles were normal. PMID- 1906436 TI - Effects of TJ-9 Sho-saiko-to (kampo medicine) on interferon gamma and antibody production specific for hepatitis B virus antigen in patients with type B chronic hepatitis. AB - To examine whether Sho-saiko-to (kampo medicine) could modulate the immune response of immunocompetent cells to hepatitis B virus (HBV)-associated antigens, we investigated in vitro interferon gamma (IFN-gamma) and antibody (antibody to HB core and e antigens; anti-HBc and anti-HBe) production by peripheral blood mononuclear cells (PBMC) from eight patients with chronic active hepatitis (CAH) (four with HBeAg and four with anti-HBe) in the presence of recombinant HBcAg and purified HBeAg. IFN-gamma and antibody production were measured using ELISA and RIA, respectively. PBMC from both HBeAg and anti-HBe positive patients generated significantly increased IFN-gamma and antibody (anti-HBc and anti-HBe) production in the culture containing Sho-saiko-to (TJ-9) in a dose-dependent manner in comparison with those of medium alone culture. Similarly, when various concentrations of TJ-9 were added to the HBV antigen-stimulated cultures, TJ-9 was found to enhance both IFN-gamma and antibody production dose-dependently. These results indicate that TJ-9 is able to modulate both cellular and humoral immune responses specific for HBV-associated antigens. These findings also may account for, at least in part, the efficacy of TJ-9 treatment for type B chronic hepatitis. PMID- 1906437 TI - The involvement of protein kinase C, calcium, and 5-lipoxygenase in the production of tumor necrosis factor by a cloned interleukin-3 dependent cell line with natural cytotoxic activity. AB - The cloned interleukin-3 dependent cell line, M1-A5 was studied to determine whether protein kinase C, calcium mobilization, and 5-lipoxygenase activity were involved in the signal transduction pathways required for the production of TNF. TNF release was stimulated by 10 ng/ml phorbol myristate acetate (PMA), 2 microM calcium ionophore A23187, and 1 microgram/ml lipopolysaccharide (LPS) with synergism seen between PMA and A23187. All signals were blocked by phloretin and the PMA signal was blocked by H-7, both drugs acting as protein kinase C inhibitors. Desensitization of protein kinase C by PMA (1 microgram/ml for 24 h) provided evidence that both PMA- and LPS-stimulated TNF production were protein kinase C-dependent while A23187-stimulated TNF production was not. Both the calcium chelator, EGTA, and the intracellular calcium antagonist, TMB-8, inhibited TNF production stimulated by all agents, indicating that TNF stimulation by all agents was calcium dependent. Finally, the 5-lipoxygenase inhibitors, ketoconazole and L-656,224, but not the cyclo-oxygenase inhibitor ASA, inhibited TNF stimulated by all agents. These findings indicate that, although TNF production by M1-A5 cells can be stimulated either by a calcium/protein kinase C- or by a calcium-dependent signal, there is a convergence of signals at the level of 5-lipoxygenase activation. PMID- 1906438 TI - In vitro activation of murine bone marrow-derived macrophages with cisplatin and mitomycin-C. AB - Peritoneal macrophages from BALB/c mice after treatment for 24 h in vitro with cisplatin, lipopolysaccharide (LPS) or mitomycin-C were rendered significantly cytotoxic against L-929 tumor target cells. In a similar experiment none of these agents could induce tumoricidal activity of fresh non-adherent bone marrow cells (NABMC). NABMC when incubated in medium alone or in medium containing L-929 culture medium (L-929 CM), a form of macrophage colony stimulating factor (M CSF), for three days matured to macrophages which were positive for non-specific esterase staining. These bone marrow-derived macrophages cultured with medium alone did not respond to cisplatin. LPS or mitomycin-C for induction of tumoricidal activity whereas bone marrow derived macrophages with that were incubated with L-929 CM showed also significantly enhanced cytotoxicity after treatment with cisplatin, LPS and mitomycin-C. Culturing of NABMC with L-929 CM significantly enhanced cell survival as compared to the cells incubated in medium alone. These results suggest that bone marrow cells not only mature in L-929 CM but also are primed by L-929 CM for induction of tumoricidal activity. PMID- 1906439 TI - Analysis of antitumor effects of OK-432 against syngeneic mouse fibrosarcoma: combination effect of OK-432 and recombinant lymphokines. AB - OK-432, a streptococcal preparation with potent biological response modifying activities, had the ability to cure mice bearing BAMC-1 (fibrosarcoma) ascites when it was injected intraperitoneally five times, 2, 4, 6, 8, and 10 days after the tumor inoculation. Previously, it was shown that the OK-432 injection on day 2 was indispensable since only a minimal antitumor effect was obtained when an inflammation-inducing agent such as thioglycolate instead of OK-432 was injected on day 2, followed by four OK-432 injections on days 4, 6, 8 and 10. In the present study, the injection of OK-432 on day 2 and a subsequent injection of either IL-2 or IFN-gamma on day 4 or 6 showed a significant antitumor effect, achieving a complete cure in approximately 50% of mice treated, although none of the mice could be cured by a single injection of either OK-432, IL-2, or IFN gamma on day 2. Interestingly, however, the mice treated with an injection of a lymphokine (IL-2 or IFN-gamma) on day 2 followed by OK-432 on day 4 were not cured either. Peritoneal cells on day 12 in mice treated with OK-432 and either of the lymphokines contained pantropic killer cells, which were Thy-1+ and asialo GM1+ (AsGM1+). Moreover, the antitumor effect of the combined treatment was abolished when mice were pre-treated with anti-AsGM1. No significant antitumor effect was observed in athymic nu/nu mice. Together with our previous findings, these results indicate that lymphokines induced by OK-432 administration may account for some of its therapeutic effects and that these lymphokines may also facilitate the subsequent induction of specific killer cells. These results warrant further investigation on possible effective therapeutic protocols with the combined use of OK-432 and lymphokines. PMID- 1906440 TI - Attorney for Cruzans discusses legal 'odyssey'. AB - On December 11, 1983, 25-year-old Missourian Nancy Cruzan was in a serious car accident, pronounced dead at the scene by police then resuscitated by paramedics. On December 14, 1990, the gastrostomy tube which had kept Nancy alive since the accident was removed and she died 11 days later. The heartbreak, legal maneuvering and impassioned discussions of the 8 years between these events captured the attention of the nation. PMID- 1906441 TI - Low doses of TRH in amyotrophic lateral sclerosis and in other neurological diseases. AB - 30 subjects--23 with amyotrophic lateral sclerosis (ALS), 4 with Charcot-Marie Tooth atrophy, 2 with progressive spinal muscle atrophy and 1 with radiation myelopathy--were given chronic low-dose TRH therapy. The effects of treatment were assessed on the scale of Norris et al. (1974). The outcome of the study, in agreement with some and at variance with other studies, was that TRH induced a statistically significant neurological improvement in 17 of the 23 ALS patients but little or none in the other ALS patients and in patients with other neurological diseases. PMID- 1906442 TI - State of stupor from valproic acid during chronic treatment: case report. AB - We describe the case of a 26 years old woman in chronic therapy with phenobarbital, carbamazepine, valproic acid (VPA) and clonazepam who showed a hyperammonemic encephalopathy after an increase in dosage of VPA. Similar cases have been reported, but with acute-subacute onset and no correlation with the plasma levels of VPA. Our case suggests the possibility that this toxic effect occurs during chronic treatment too, when the dosage of VPA is increased. PMID- 1906443 TI - Dysrhythmias and blood pressure changes associated with thrombolysis. AB - Recent technologic advances facilitate salvage of viable myocardium before the process of myocardial infarction is complete. The aim of thrombolytic agents is to restore antegrade flow of blood in occluded coronary arteries. The process of reperfusion may be dysrhythmogenic because of the heterogeneous return of electrical activity in myocardial cells. This study examined the incidence and type of dysrhythmia occurrence and the associated changes in mean arterial blood pressure (MAP) during infusion of tissue-type plasminogen activator (TPA). A retrospective chart review of 41 subjects showed that 80% of subjects experienced dysrhythmias during TPA therapy. The most common dysrhythmia was sinus bradycardia, followed by idioventricular/accelerated idioventricular rhythm, ventricular premature beats, and ventricular tachycardia/fibrillation. There was a significant difference between MAP changes when there were no dysrhythmias and MAP changes when dysrhythmias occurred (p less than 0.05). The largest change in MAP (-22.71 mm Hg) was observed when dysrhythmias occurred in those subjects with blockage of the left anterior descending artery, although there was no statistically significant difference in changes in MAP among the groups of different sites of blockage (p greater than 0.05). PMID- 1906444 TI - Management of the patient with do not resuscitate status: compassion and cost containment. AB - An interdisciplinary approach to the management of patients with do not resuscitate status on a supportive care team is an alternative to traditional intensive care unit management. This approach focuses on the physical, psychological, and spiritual needs of the patient and family. We describe our experience with 131 patients managed by the supportive care team that resulted in humane care of dying patients and reduced hospital costs as evidenced by reduced Therapeutic Intervention Scoring System values. Although our goal is comprehensive terminal care, financial savings have resulted as well. We describe the elements of care that contribute to compassionate management and to reduced interventions and costs. This approach may have application in other critical care settings that are faced with the same challenges of providing humane care to hopelessly ill patients. PMID- 1906445 TI - Use of capnography in critically ill adults. AB - A major responsibility of the critical care practitioner is to assure adequate ventilation of the critically ill patient. The traditionally used methods for evaluating ventilation, such as physical examination and measurement of vital signs, are indirect. The most commonly used direct method, measurement of arterial carbon dioxide tension, is invasive and intermittent. Capnography provides the critical care practitioner with a continuous, noninvasive, and accurate assessment of ventilation. To interpret capnographic data, the practitioner must have a clear understanding of normal and abnormal patterns of carbon dioxide elimination in the lung. We review relevant respiratory physiology as a basis for understanding the value of capnography. The technology on which capnography is based is described with emphasis on methods of gas sampling, limitations of capnography, and features available on currently marketed instruments. Representative capnograms are presented and the data interpreted to enable the practitioner to determine when capnography is an appropriate monitor for the critically ill adult. PMID- 1906446 TI - Flow characteristics of enteral feeding with psyllium hydrophilic mucilloid added. AB - One therapy for managing diarrhea in patients in intensive care units who are receiving enteral nutrition is administration of psyllium hydrophilic mucilloid (PHM). This laboratory study was conducted to determine whether the addition of PHM (Metamucil) to enteral feeding formula (Entrition) adversely affected the flow characteristics of the feeding formula through a small-bore feeding tube. Descriptive data were obtained from 72 trials of feeding formula with varied infusion rates, formula osmolality and temperature, and PHM concentrations. Two thirds (n = 48) of the trials were successful (PHM did not clog the tubing and obstruct flow). The remaining one third of the trials (n = 24) were unsuccessful. Successful formula infusion was influenced by formula temperature and osmolality but not by infusion rate, PHM concentration, or flow interruption. If formula with PHM was followed by formula without PHM, the infusion was successful regardless of infusion rate or formula osmolality. Thus, the data from this laboratory study indicate that when therapeutic doses of PHM are prescribed, it is feasible for PHM to be mixed in room-temperature feeding formula and infused without clogging the feeding tube. PMID- 1906447 TI - Effect of a bulk-forming cathartic on diarrhea in tube-fed patients. AB - Diarrhea is a significant complication for the patient being tube-fed. The purpose of this study was to observe whether giving a bulk-forming cathartic to patients receiving enteral nutrition via nasogastric or nasoduodenal tube would result in firmer stools for these patients. Forty-nine patients in a large medical center were randomly assigned to either a control or an experimental group. During the 6-day study period 1 teaspoon (5 ml) of psyllium preparation was administered through the feeding tube three times a day. Data were analyzed by using the Mann-Whitney U test for nonparametric data. The hypothesis that giving a bulk-forming cathartic would lead to firmer stools was supported at an alpha level of less than 0.01. The results of this study suggest that use of a bulk-forming cathartic in tube-fed patients will significantly reduce the diarrhea associated with this type of feeding. PMID- 1906448 TI - Incidence of pulmonary aspiration in intubated patients receiving enteral nutrition through wide- and narrow-bore nasogastric feeding tubes. PMID- 1906449 TI - A monoclonal antibody reacting with platelets for monitoring thrombolysis. AB - Thrombus immunoscintigraphy with radiolabeled monoclonal antibodies are presently undergoing intense clinical evaluations. Reports on clinical trials of radiolabeled antifibrins are very encouraging and results of antiplatelet antibody evaluations are forthcoming. Animal studies with antiplatelet antibodies indicate that a diagnosis can be made within the critical "lytic window" of 4-6 h, and thus the imaging procedure may be used as an adjunct to thrombolytic therapy, i.e. screening of patients. We now report on a potentially new application of monoclonal antibodies, immunoimaging for monitoring thrombolysis. In vitro studies were performed with "standardized clots" incubated with 99mTc 50H.19 and re-incubated with streptokinase (SK), urokinase (UK) or recombinant tissue plasminogen activator (rt-PA). The decrease in clot-bound 99mTc 50H.19 activity after SK, UK or rt-PA incubation was proportional to the decrease in clot weight (r = 0.90-0.98). The direct effects of these thrombolytic agents on the labeled antibody and the possible interference of aspirin, warfarin and heparin in thrombus immunoimaging were also investigated. Aspirin, heparin and warfarin did not interfere with clot-binding of 99mTc 50H.19. Thrombolytic agents did not affect the stability of the radiolabel or immunoreactivity of 50H.19. These results indicate that 99mTc 50H.19 is a promising agent that may enable monitoring thrombolysis in addition to thrombus immunoimaging. PMID- 1906450 TI - Electron micrograph maps of divisions 51 through 60 of thin sectioned polytene 2R chromosome of Drosophila melanogaster. AB - The banding pattern of the distal half, i.e., the divisions 51 through 60, of the salivary gland 2R chromosome in Drosophila melanogaster was studied using thin section electron microscopy. This chromosome region contains 280 single and 157 double bands on the Bridges' revised light microscopic map. Most of the single bands were identified in thin sections; 34 bands were regarded as missing or they could not be reliably shown. In addition, about 20 new, mainly very faint single bands were found. 21 Bridges' double bands were found to be made up of two separate bands each in thin sections. PMID- 1906451 TI - Novel and potent gastrin and brain cholecystokinin antagonists from Streptomyces olivaceus. Taxonomy, fermentation, isolation, chemical conversions, and physico chemical and biochemical properties. AB - The discovery and physico-chemical characterization of three novel and minor virginiamycin M1 analogs as potent gastrin antagonists from a culture of a strain of Streptomyces olivaceus are described. These analogs are L-156,586, L-156,587 and L-156,588. They are, respectively, 15-dihydro-13,14-anhydro-, 13,14-anhydro- and 13-desoxy-analogs of virginiamycin M1. We also chemically converted virginiamycin M1 (via L-156,587) to L-156,586 and its unnatural epimer, L 156,906. These analogs are competitive and selective antagonists of gastrin and brain cholecystokinin binding at nanomolar concentrations. These are the most potent gastrin/brain cholecystokinin antagonists from natural products. The same compounds showed poor Gram-positive antibiotic activity versus virginiamycin M1. Structurally related Gram-positive antibiotics, griseoviridin and madumycin I, were inactive in gastrin and brain cholecystokinin binding at up to 100 microM. PMID- 1906452 TI - Metabolic products of microorganisms. 258. Enzymatic bromination of nikkomycin Z. AB - Two brominated nikkomycins were produced by enzymatic halogenation of nikkomycin Z in the presence of a nonheme bromoperoxidase isolated from Streptomyces aureofaciens Tu 24. The monobrominated and dibrominated nikkomycin Z derivatives were substituted at the hydroxypyridyl moiety of the N-terminal amino acid of nikkomycin Z at position C-6"' (ZBr) or C-4"' and C-6"' (ZBr2). The brominated nikkomycin Z derivatives had a decreased affinity to chitin synthase of Coprinus cinereus as compared to nikkomycin Z and exhibited a low inhibitory activity towards various fungi and yeasts. PMID- 1906453 TI - Secondary metabolites by chemical screening, 15. Structure and absolute configuration of naphthomevalin, a new dihydro-naphthoquinone antibiotic from Streptomyces sp. PMID- 1906454 TI - Influence of direction of body weight change on pattern of gonadotropin secretion in ovariectomized beef heifers of equivalent body weight. AB - Our hypothesis was that alterations in pattern of gonadotropin secretion induced by level of dietary energy intake are dependent on direction of BW change. Beef heifers were assigned to one of two treatments 21 d after ovariectomy: 1) increasing followed by decreasing BW (I-D; n = 9) or 2) decreasing followed by increasing BW (D-I; n = 9). Heifers assigned to the I-D treatment received 15.4 Mcal ME/d (HE) from wk 0 to 8 followed by 4.3 Mcal ME/d (LE) from wk 9 to 16. Heifers assigned to the D-I treatment received the LE diet for the initial 8 wk followed by the HE diet for the subsequent 8 wk. At 2-wk intervals blood samples were collected at 10-min intervals for 11 h to determine the pattern of secretion and(or) concentration of gonadotropins in circulation (LH and FSH) and pituitary responsiveness to administration of 750 ng and 50 micrograms of LHRH. Frequency of LH pulses increased (P less than .05) in a quadratic fashion with increasing ADG in heifers in both treatment groups. Amplitude of LH pulses decreased (P less than .05) in a linear fashion with increasing ADG in heifers in both treatment groups and magnitude of this decline was greater (P less than .05) in heifers receiving the D-I treatment. Amplitude of response to 750 ng of LHRH decreased (P less than .05) in a linear fashion with increasing ADG in heifers receiving the D I treatment but was unrelated to changes in ADG (P greater than .05) in heifers receiving the I-D treatment. When heifers in both treatment groups attained similar BW (P greater than .05; wk 14), amplitude of LH pulses, responsiveness to 750 ng of LHRH and mean concentration of FSH in serum were higher (P less than .05) in heifers receiving the I-D than in heifers receiving the D-I treatment. Thus, we accept the hypothesis that alterations in pattern of gonadotropin secretion in heifers fed diets with a low energy content are dependent on direction of BW change. PMID- 1906455 TI - Energy utilization and organ mass of Targhee sheep selected for rate and efficiency of gain and receiving high and low planes of nutrition. AB - Two experiments were conducted to examine changes in usage of energy and visceral organ mass in Targhee lambs selected on the basis of improved rate and efficiency of growth. In Exp. 1, Targhee ram lambs from a breeding line selected for improved growth rate and feed efficiency and a control line that was maintained without selection for 20 yr were provided with either a high (ad libitum) or low (maintenance) plane of nutrition. Rams were slaughtered and weights of the visceral organs were recorded. Analysis of variance, using a factorial model with BW as a covariant, was used to examine effects of lines of breeding, plane of nutrition, interaction between line of breeding and plane of nutrition, and days on feed. Weights of liver, kidneys, rumen, abomasum, and small and large intestines from lambs receiving a high plane of nutrition were, respectively, 39, 25, 12, 28, 40, and 31% greater than weights of those tissues in lambs receiving a low plane of nutrition. Ruminal weights were 13% greater for rams from the select line of breeding than for those from the control line. In Exp. 2, seven Targhee ewe lambs from the select line and eight from the control line were examined for differences in heat production and energy usage by indirect open circuit respiration calorimetry using a completely randomized design. Fasting heat production of lambs from the select line was 7.8% greater than that of lambs from the control line. Partial efficiencies of ME used for maintenance and tissue accretion were not different between lines of breeding.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1906456 TI - A serum-free medium for the culture of insect cells and production of recombinant proteins. AB - A low protein aqueous lipid supplement (Ex-Cyte VLE), in combination with pluronic polyol, is an effective replacement for fetal bovine serum for insect Sf 9 cells. Serum-free medium with lipid supplement and pluronic (SFM-LP) supported higher cell viability and maximum cell populations than serum-supplemented medium. No adaptation procedures are required when switching cells from serum containing medium to SFM-LP, and growth rates remain constant during continued passages in SFM-LP. The amounts of recombinant proteins produced, which is the major use for the Sf-9 cells, are better or equal in SFM-LP compared to serum supplemented medium. SFM-LP also supports growth of the TN-368 cell line but IPLB SF-21AE or IZD-Mb0503 lines grow poorly in this medium. PMID- 1906457 TI - Usefulness of intracoronary injection of acetylcholine as a provocative test for coronary artery spasm in patients with vasospastic angina. AB - In order to examine both the sensitivity and specificity of coronary artery spasm induced by intracoronary injection of acetylcholine in patients with vasospastic angina, incremental doses of acetylcholine (20, 30, and 50 micrograms) were injected directly into each coronary artery in 21 patients with variant angina (group A), in 28 patients with other types of vasospastic angina (group B), and in 20 patients without any significant coronary artery disease (group C). Coronary artery spasm was defined as severe vasoconstriction (greater than or equal to 90% of reduction in luminal diameter) with chest pain and/or ischemic changes in the electrocardiogram. Intracoronary injection of acetylcholine induced spasm of at least one coronary artery in 20 patients (95%) of group A, in 27 patients (96%) of group B, and in only 2 patients (10%) of group C. The low dose of acetylcholine (20 micrograms) induced coronary spasm more frequently in group A patients (81%) than in group B patients (43%) (P less than 0.05). ST segment elevation associated with anginal attacks was significantly (P less than 0.05) more frequent in group A (71%) than in group B (39%). When acetylcholine was injected separately into the left and right coronary arteries, spasm of both coronary arteries was observed in 7 out of 14 of group A (50%), in 8 out of 22 of group B (36%), and in none of the 20 of group C. We concluded that intracoronary injection of acetylcholine is a sensitive and reliable method for the induction of coronary spasm in patients with vasospastic angina as well as in those with variant angina. PMID- 1906458 TI - Metabolism of two Go alpha isoforms in neuronal cells during differentiation. AB - We have previously shown that undifferentiated N1E-115 neuroblastoma cells express only one isoform of Go alpha (pI = 5.8), whereas differentiated neuroblastoma cells expressed, in addition to this isoform, another Go alpha with a more acidic pI (5.55). Moreover, primary cultures of cerebellar granule cells, which are extremely well differentiated cells yielding a high density of synapses, expressed only a single Go alpha isoform with a pI of 5.55 (Brabet, P., Pantaloni, C., Rodriguez Martinez, J., Bockaert, J., and Homburger, V. (1990) J. Neurochem. 54, 1310-1320). In this report, using biosynthetic labeling with [35S]methionine and specific quantitative immunoprecipitation with a polyclonal antibody raised against the purified Go alpha protein, we have determined 1) the degradation rate of total Go alpha (sum of the two isoforms) in differentiated as well as in undifferentiated neuroblastoma cells and in cerebellar granule cells, 2) the degradation rates of each isoform in differentiated neuroblastoma cells. The t 1/2 for total Go alpha protein degradation was very different in the three neuronal cell populations and was 28 +/- 5 h (n = 5), 58 +/- 9 h (n = 5), and 154 +/- 22 h (n = 6) in undifferentiated, differentiated neuroblastoma, and granule cells, respectively. Using two-dimensional gel analysis of immunoprecipitates, we have also determined the individual t 1/2 for degradation of each Go alpha isoform in differentiated neuroblastoma cells, in which the two Go alpha isoforms were expressed. Results indicated that the two Go alpha isoforms exhibit similar t1/2 for degradation (49 +/- 5 h, n = 3). Thus, the t1/2 for degradation of the more basic Go alpha isoform is higher in differentiated neuroblastoma cells (49 +/- 5 h, n = 3) than in undifferentiated neuroblastoma cells (28 +/- 5 h, n = 5) which expressed only the more basic Go alpha isoform. It can be concluded that the degradation rate of the more basic Go alpha isoform is not a characteristic of the protein itself but depends on the state of the cell differentiation. The comparison between the t1/2 for degradation of the more acidic Go alpha isoform is differentiated neuroblastoma cells (51 +/- 6 h, n = 3) with that of cerebellar granule cells (154 +/- 22 h, n = 6) suggests that there is also a decrease in the degradation rate of the more acidic Go alpha isoform during differentiation.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1906460 TI - H218O isotope exchange studies on the mechanism of reduction of nitric oxide and nitrite to nitrous oxide by denitrifying bacteria. Evidence for an electrophilic nitrosyl during reduction of nitric oxide. AB - Reduction of NO and NO2-by whole cells of eight strains of denitrifying bacteria known to contain either heme cd1 or copper-containing nitrite reductases (NiRs) has been examined in the presence of H218O. All organisms containing heme cd1 NiRs exhibited relatively large extents of exchange between NO2- and H218O (39 100%), as monitored by the 18O content of product N2O. Organisms containing copper NiRs gave highly variable results, with Achromobacter cycloclastes and Pseudomonas aureofaciens exhibiting no 18O incorporation and Rhodopseudomonas sphaeroides and Alcaligenes entrophus exhibiting complete exchange between NO2- and H218O. Organisms containing heme cd1 NiRs exhibited significant but lower levels of exchange between NO and H218O than between NO2- and H218O, while organisms containing copper NiRs gave significantly higher amounts of 18O incorporation than observed for the heme cd1 organisms. These results demonstrate the existence of an NO-derived species capable of undergoing O-atom exchange with H218O during the reduction of NO. Trapping experiments with 15NO, 14N3-, and crude extracts of R. sphaeroides support the electrophilic nature of this intermediate and suggest its formulation as an enzyme nitrosyl, E-NO+, analogous to that observed during reduction of NO2-. The observation of lower levels of 18O incorporation with NO2- than with NO as substrate for A. cycloclastes and P. aureofaciens indicates that, for these organisms at least, a sequential pathway involving free NO as an intermediate is significantly less important than a direct pathway in which N2O is formed via reaction of two NO2- ions on a single enzyme. PMID- 1906459 TI - Evidence that the nonparenchymal cells of the liver are the principal source of cholesteryl ester transfer protein in primates. AB - Previous studies showed that 90% or more of the cholesteryl ester transfer protein (CETP) mRNA is contained in the liver of cynomolgus monkeys. The purpose of this study was to determine if the parenchymal cells (hepatocytes) were the hepatic cell type that contained that mRNA. The parenchymal and nonparenchymal cells were separated by standard methods, and the CETP, apoA-I, apoB, and apoE mRNA content of the preparation determined at each step in the purification process. ApoA-I and apoB are produced only in the parenchymal cells; apoE is produced by both cell types. The mRNA measurements showed that the CETP mRNA: apoA-I mRNA and the CETP mRNA: apoB mRNA ratios were more than 2500-fold greater in the nonparenchymal cell preparation than in the starting material, and that the purified parenchymal cell fraction was virtually devoid of CETP mRNA. In situ hybridization studies showed that, whereas the apoA-I mRNA signal was evenly distributed over the tissue section, the CETP mRNA signal was associated with the hepatic sinusoids, suggesting that it was the hepatic sinusoidal cells that were principally responsible for the high CETP mRNA levels in the liver. We conclude that the nonparenchymal cells are the principal source of CETP in the cynomolgus monkey. PMID- 1906461 TI - High affinity interactions between the Alzheimer's beta-amyloid precursor proteins and the basement membrane form of heparan sulfate proteoglycan. AB - High affinity interactions were studied between the basement membrane form of heparan sulfate proteoglycan (HSPG) and the 695-, 751-, and 770-amino acid Alzheimer amyloid precursor (AAP) proteins. Based on quantitative analyses of binding data, we identified single binding sites for the HSPG on AAP-695 (Kd = 9 x 10(-10) M), AAP-751 (Kd = 10 x 10(-9) M), and AAP-770 (Kd = 9 x 10(-9) M). It is postulated that the "Kunitz" protease inhibitor domain which is present in AAP 751 and -770 reduces the affinity of AAPs for the HSPG through steric hindrance and/or conformational alteration. HSPG binding was inhibited by heparin and dextran sulfate, but not by dermatan or chondroitin sulfate. HSPG protein core, obtained by heparitinase digestion, also bound to the beta-amyloid precursor proteins with high affinity, indicating that the high affinity binding site is constituted by the polypeptide chain rather than the carbohydrate moiety. The effects of various cations on these interactions were also studied. Our results suggest that specific interactions between the AAP proteins and the extracellular matrix may be involved in the nucleation stages of Alzheimer's disease type amyloidogenesis. PMID- 1906462 TI - Domain structure and domain-domain interactions of recombinant tissue plasminogen activator. AB - The melting of recombinant tissue plasminogen activator (rtPA) has been investigated by differential scanning calorimetry and fluorescence spectroscopy. At neutral pH, rtPA melts with only partial reversibility in a single sharp peak that can be deconvoluted into four transitions. By contrast, at acidic pH the melting process is spread over a broad range of temperature and is highly reversible. Under these conditions five transitions are resolved by deconvolution analysis. Additional measurements in 6 M guanidinium chloride reveal a sixth transition representing an extremely stable domain. Comparison of the melting curves of several fragments with those of the parent protein allowed all of the transitions to be assigned. The results indicate that rtPA is comprised of six independently folded domains. Two of these domains correspond to the two kringle modules whose thermodynamic properties are similar to those of the kringles in plasminogen. Two additional domains are formed by the epidermal growth factor (EGF)-like and finger modules, the latter of which is extremely stable, requiring the presence of a chemical denaturant for its melting to be observed. The serine protease module contains two more domains which at neutral pH melt cooperatively in a single transition but at low pH melt independently, accounting for the greater number of transitions observed there. Measurements with a 50-kDa fragment lacking the C-terminal half of the serine protease module and with a variant lacking the finger and EGF domains indicate that the serine protease domains interact strongly with and are stabilized by the finger and/or EGF domains in the intact protein. This interaction between domains located at opposite ends of the rtPA molecule produces a more compact structure. A better understanding of such interactions may enhance efforts to engineer plasminogen activators with improved thrombolytic properties. PMID- 1906463 TI - Interpretation of the spectra observed during oxidation of p-hydroxybenzoate hydroxylase reconstituted with modified flavins. AB - Oxidation of reduced p-hydroxybenzoate hydroxylase by oxygen in the presence of 2,4-dihydroxybenzoate and azide proceeds via three well established intermediates. Reconstitution of the apoprotein with either 8-thiophenyl-FAD, 8 fluoro-FAD, 8-chloro-FAD, or 8-sulfonyl-FAD does not alter this sequence of events. However, the peak positions of the intermediate spectra are somewhat shifted relative to those of native enzyme. Comparison of the spectra for intermediates II and III leads to the conclusion that the spectrum for intermediate II is a composite. One component is the spectrum of an intermediate III-like species, and the other appears to be related to the substrate. The substrate component is pH-dependent, having an absorbance maximum of 386 nm (extinction, approximately 6,000 M-1 cm-1) at pH 6.6 which shifts to approximately 430 nm (extinction, approximately 11-13,000 M-1 cm-1) at pH 9.2, with a pK of 7.9. The pH dependence for the spectrum of the substrate component combined with the pH independence of the intermediate III-like spectrum satisfactorily accounts for the pH dependence observed for intermediate II, including the fact that the high pH spectrum of native intermediate II is qualitatively quite different from that of 8-sulfonyl-FAD intermediate II. PMID- 1906464 TI - Location of the mycolyl ester substituents in the cell walls of mycobacteria. AB - The question of the precise location of mycolic acids, the single most distinctive cell wall entity of members of the Mycobacterium genus, has now been addressed. The free hydroxyl functions of the arabinogalactan component of the mycobacterial cell wall were O-methylated under conditions in which the mycolyl esters were not cleaved. Subsequent replacement of the mycolyl functions with O ethyl groups resulted in an acid- and base-stable differentially O-alkylated surrogate polysaccharide, more amenable to analysis. Complete hydrolysis, reduction, acetylation, and gas chromatography/mass spectrometry revealed the unexpected finding that the mycolyl substituents were selectively and equally distributed on the 5-hydroxyl functions of terminal- and 2-linked arabinofuranosyl (Araf) residues. Further analysis of the O-alkylated cell wall through partial acid hydrolysis, NaB[2H]4 reduction, pentadeuterioethylation, and gas chromatography/mass spectrometry demonstrated that the mycolyl units are clustered in groups of four on the previously recognized nonreducing terminal pentaarabinosyl unit [beta-Araf-(1----2)-alpha-Araf)2-3, 5-alpha-Araf. However, only about two-thirds of the available pentasaccharide units are so substituted. Thus, the antigenicity of the arabinan component of mycobacterial cell walls may be explained by the fact that about one-third of the pentaarabinosyl units are not mycolyated and are available for interaction with the immune system. On the other hand, the extreme hydrophobicity and impenetrability of the mycobacterial cell may be explained by the same motif also acting as the fulerum for massive esterified paraffin residues. New fundamental information on the structure of mycobacterial cell walls will aid in our comprehension of its impenetrability to antibiotics and role in immunopathogenesis and persistence of disease. PMID- 1906465 TI - Acquisition of the functional properties of the transferrin receptor during its biosynthesis. AB - The properties of the newly synthesized and partially glycosylated forms of the transferrin receptor were examined to determine which co- and post-translational modifications are necessary for the acquisition of transferrin binding activity and transport of the receptor to the cell surface. The nascent transferrin receptor containing core-glycosylated asparagine-linked oligosaccharides does not possess complete intersubunit disulfide bonds, sediments predominantly as a monomer in sucrose density gradients, and shows reduced binding to transferrin agarose. Within 20-30 min after synthesis, the transferrin receptor acquires the ability to bind to a transferrin-linked affinity column. Intersubunit disulfide bond formation occurs slowly throughout the transit of the receptor to the cell surface. These results indicate that core glycosylation of the receptor may be necessary but is not sufficient for the acquisition of the ability of the receptor to bind transferrin and that intersubunit disulfide bond formation is a post-translational event. Inhibition of complex carbohydrate synthesis by either swainsonine (1 micrograms/ml) or deoxynojirimycin (4 mM) does not inhibit the ability of this receptor to form intersubunit disulfide bonds or to be transported to the cell surface. The partially glycosylated receptor, however, does show an approximately 3-fold reduced affinity for transferrin. PMID- 1906466 TI - Inhibition of degradation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase in vivo by cysteine protease inhibitors. AB - 3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase is a key regulatory enzyme of cholesterol biosynthesis and is located in the endoplasmic reticulum (ER). A fusion protein, HMGal, consisting of the membrane domain of HMG-CoA reductase fused to Escherichia coli beta-galactosidase and expressed in Chinese hamster ovary (CHO) cells from the SV40 promoter, was previously constructed and was found to respond to regulatory signals for degradation in a similar fashion to the intact HMG-CoA reductase. Degradation of both HMG-CoA reductase and HMGal in CHO cells was enhanced by addition of mevalonate or low density lipoprotein (LDL). In this report we show that 2 cysteine protease inhibitors, N-acetyl leucyl-leucyl-norleucinal (ALLN) and N-acetyl-leucyl-leucyl-methioninal (ALLM), completely inhibit the mevalonate- or LDL-accelerated degradation of HMG-CoA reductase and HMGal and also block the basal degradation of these enzymes. It has been shown that in vitro these protease inhibitors inhibit the activities of Ca(2+)-dependent neutral proteases as well as lysosomal proteases, including cathepsin L, cathepsin b, and cathepsin D. However, the mevalonate-accelerated degradation of HMG-CoA reductase and HMGal is not affected by lysosomotropic agents, suggesting that the site of action of these inhibitor peptides in preventing the degradation is not the cathepsins. In brefeldin A-treated cells, where protein export from the ER is blocked, ALLN is still effective in inhibiting the degradation of HMG-CoA reductase and HMGal. These results indicate the involvement of non-lysosomal Ca(2+)-dependent proteases in the basal and the accelerated degradation of HMG-CoA reductase and HMGal. Enzymatic assays in vitro and immunoblot analyses have revealed calpain- and calpastatin-like proteins in CHO cells. The activities and the amount of these proteins do not change under conditions of enhanced degradation, indicating that the levels of these proteins are not subject to mevalonate regulation. PMID- 1906467 TI - The transition state regulator Hpr of Bacillus subtilis is a DNA-binding protein. AB - The synthesis of a variety of proteins, including the well characterized degradative enzymes, which occurs during the transition state between vegetative growth and the onset of sporulation in Bacillus subtilis is controlled by a class of molecules known as transition state regulators. One of these regulators is the product of the hpr gene, first identified by mutations affecting the synthesis of extracellular proteases. We have purified the Hpr protein and found that it binds specifically to DNA fragments carrying the promoters and the upstream regions of the alkaline (aprE) and neutral (nprE) protease genes of B. subtilis. DNase I protection experiments revealed that the Hpr protein is able to bind at four and two regions of the aprE and nprE promoters, respectively. We have also located two Hpr binding sites in the promoter region of a gene of unknown function which is nevertheless known to be developmentally regulated during the transition state and which occurs in the same operon as the gene encoding another transition state regulator, Sin. The location of one of the Hpr binding sites on the aprE gene occurs adjacent to a region to which the Sin protein binds. However, in mixing competition experiments we have shown that Hpr and Sin binding occurred independently, and no visible alterations of protected regions were detected. PMID- 1906468 TI - Effect of aspirin on heterotopic ossification after total hip arthroplasty in men who have osteoarthrosis. AB - The severity of heterotopic ossification was determined from the radiographs of eighty-three men in whom osteoarthrosis had been treated with a primary total hip arthroplasty with cement. The medical records of these patients were then reviewed, with the reviewer having no knowledge of the radiographic findings. A similar operative approach and technique had been used in all patients. There was no association between the amount of intraoperative loss of blood or the duration of the operation and the severity of formation of heterotopic bone. The over-all rate of occurrence of heterotopic ossification was 72 per cent. Of the fifty eight patients who had received aspirin throughout their course in the hospital, two (3 per cent) had severe ectopic ossification (grade III or IV8). In contrast, twelve (48 per cent) of the twenty-five patients who had received no aspirin or in whom aspirin had been discontinued so that anticoagulation could be begun had severe heterotopic ossification. The difference in the severity of the ossification between the two groups is significant (p less than 0.0001). PMID- 1906469 TI - Prevention of formation of heterotopic bone after total hip arthroplasty. PMID- 1906470 TI - Clinical and radiographic evaluation of total hip replacement. A standard system of terminology for reporting results. PMID- 1906471 TI - Heterotopic ossification about the hip after intramedullary nailing for fractures of the femur. PMID- 1906472 TI - Postoperative blood salvage in total hip and knee arthroplasty. A randomised controlled trial. AB - We undertook a prospective controlled clinical trial of 109 patients to determine whether postoperative blood salvage in patients undergoing total hip or knee arthroplasty decreased the need for transfusion with banked blood. The average amount of blood collected in our series was 493 ml, most of which was collected in the first four postoperative hours. In patients undergoing bilateral total knee arthroplasty, there was a 54% reduction in banked blood utilisation. None of our patients developed adverse effects from the reinfused material. The cost of collecting and processing wound drainage using the Haemolite cell washer was $175 per patient, regardless of the volume processed, compared to $125 for a unit of banked blood. By reducing the requirement for homologous transfusion, blood salvage diminishes the risks of transmission of HIV and hepatitis viruses. In those cases where the equivalent of two units of blood are reinfused, blood salvage saves money. However, due to the small amounts of blood collected in unilateral hip or knee arthroplasty, we do not recommend its routine application in these cases. PMID- 1906473 TI - Dysplasia epiphysealis capitis femoris. Meyer's dysplasia. AB - We made a prospective longitudinal clinical and radiological study of 18 children diagnosed as having dysplasia epiphysealis capitis femoris. Half the cases were bilateral. Boys were affected five times more often than girls. There were no symptoms or clinical signs in most but some of the bilateral cases had an inconsistent waddling gait. The imaging studies suggest that the cartilaginous proximal femoral epiphysis is hypoplastic, with delayed appearance of single or multiple ossification centres. Progressive improvement occurred and at an average age of five years and six months, there was complete fusion of all the ossific nuclei and normal density and texture of the epiphyseal bone. The end result was a round epiphysis with a slightly diminished height. The dysplasia is attributed to focal hypoplasia of the proximal femoral epiphysis. PMID- 1906474 TI - Synapsin I-mediated interaction of brain spectrin with synaptic vesicles. AB - We have established a new binding assay in which 125I-labeled synaptic vesicles are incubated with brain spectrin covalently immobilized on cellulosic membranes in a microfiltration apparatus. We obtained saturable, high affinity, salt- (optimum at 50-70 mM NaCl) and pH- (optimum at pH 7.5-7.8) dependent binding. Nonlinear regression analysis of the binding isotherm indicated one site binding with a Kd = 59 micrograms/ml and a maximal binding capacity = 1.9 micrograms vesicle protein per microgram spectrin. The fact that the binding of spectrin was via synapsin was demonstrated in three ways. (a) Binding of synaptic vesicles to immobilized spectrin was eliminated by prior extraction with 1 M KCl. When the peripheral membrane proteins in the 1 M KCl extract were separated by SDS-PAGE, transferred to nitrocellulose paper and incubated with 125I-brain spectrin, 96% of the total radioactivity was associated with five polypeptides of 80, 75, 69, 64, and 40 kD. All five polypeptides reacted with an anti-synapsin I polyclonal antibody, and the 80- and 75-kD polypeptides comigrated with authentic synapsin Ia and synapsin Ib. The 69- and 64-kD polypeptides are either proteolytic fragments of synapsin I or represent synapsin IIa and synapsin IIb. (b) Pure synapsin I was capable of competitively inhibiting the binding of radioiodinated synaptic vesicles to immobilized brain spectrin with a Kl = 46 nM. (c) Fab fragments of anti-synapsin I were capable of inhibiting the binding of radioiodinated synaptic vesicles to immobilized brain spectrin. These three observations clearly establish that synapsin I is a primary receptor for brain spectrin on the cytoplasmic surface of the synaptic vesicle membrane. PMID- 1906476 TI - Application of reversed-phase high-performance liquid chromatography to the separation of apolipoproteins A-IV, A-I and E from rat high-density lipoprotein. AB - Apolipoproteins A-IV, A-I and E from rat high-density lipoprotein (HDL) were successfully purified by reversed-phase high-performance liquid chromatography (RP-HPLC), using a method which we have previously developed for the separation of apolipoproteins A-IV, A-I and E from human lymph chylomicrons [T. Tetaz, E. Kecorius, B. Grego and N. Fidge, J. Chromatogr., 511 (1990) 147]. Since analytical-scale RP-HPLC indicated that the C apolipoproteins from rat HDL coeluted with both apo A-IV and apo A-I, delipidated rat HDL was first subjected to preparative-scale size-exclusion HPLC (HPSEC) on a Serva Si300 column, which effectively separated the C apolipoproteins from all but apolipoprotein E. Fractions from HPSEC which were enriched for apolipoproteins A-IV, A-I or E were directly applied to RP-HPLC on a TSK Phenyl-5PW column. This procedure yielded fractions containing apolipoproteins A-IV, A-I or E which were pure as assessed by N-terminal sequencing and silver staining of sodium dodecyl sulphate polyacrylamide gels. PMID- 1906477 TI - Why certification/accreditation? PMID- 1906475 TI - The primary structure of NG2, a novel membrane-spanning proteoglycan. AB - The complete primary structure of the core protein of rat NG2, a large, chondroitin sulfate proteoglycan expressed on O2A progenitor cells, has been determined from cDNA clones. These cDNAs hybridize to an mRNA species of 8.9 kbp from rat neural cell lines. The total contiguous cDNA spans 8,071 nucleotides and contains an open reading frame for 2,325 amino acids. The predicted protein is an integral membrane protein with a large extracellular domain (2,224 amino acids), a single transmembrane domain (25 amino acids), and a short cytoplasmic tail (76 amino acids). Based on the deduced amino acid sequence and immunochemical analysis of proteolytic fragments of NG2, the extracellular region can be divided into three domains: an amino terminal cysteine-containing domain which is stabilized by intrachain disulfide bonds, a serine-glycine-containing domain to which chondroitin sulfate chains are attached, and another cysteine-containing domain. Four internal repeats, each consisting of 200 amino acids, are found in the extracellular domain of NG2. These repeats contain a short sequence that resembles the putative Ca(++)-binding region of the cadherins. The sequence of NG2 does not show significant homology with any other known proteins, suggesting that NG2 is a novel species of integral membrane proteoglycan. PMID- 1906478 TI - A summer institute on computer applications for nursing management: background, curriculum, and evaluation. AB - Nursing managers are faced with a growing number of computer applications for nursing management, yet they may lack the educational preparation to assist them in using these technologies for problem-solving and decision-making. This article describes a Summer Institute on informatics applications for nursing management taught by an international and multidisciplinary team of faculty members, and offered at the University of Limburg (Maastricht, The Netherlands). A discussion of professional, scientific, and educational issues serves as the foundation for curriculum content and instructional format. Evaluation data from both offerings are reviewed and underscore the professional relevance and didactic quality of the Summer Institute. The Summer Institute is presented as a possible model of continuing education in computer applications for nursing management transferable to Western European and North American countries. PMID- 1906479 TI - Educating nurses in political process: a growing need. AB - If we are to advance the profession of nursing, we must educate nurses to become key participants in the formulation of health policy. If we fail to do this, others will make decisions that affect our practice without our input. A growing number of nurses are recognizing the need to increase our power, and we understand that political participation provides a pathway to power. We must continue to increase the number of nurses who are politically astute and active in order to achieve our goal. The most effective way to accomplish this is to educate large numbers of staff nurses for this vital role. This article suggests educational strategies and methods that can be utilized in continuing education programs to begin the political education process. PMID- 1906480 TI - Innovative approaches to inservice education. AB - The many challenges facing nursing educators today include meeting the regulatory agency education standards while reaching staff on a variety of shifts/schedules. This article describes a model for the development, implementation, and evaluation of required inservice education that meets this challenge. Creative teaching strategies are discussed that facilitate learning at the individual level, encourage staff participation at the unit level, and contain costs at the department level. PMID- 1906481 TI - An emergency pursuit game: a method for teaching emergency decision-making skills. AB - Continuing education programs are used to enhance nurses' emergency decision making knowledge and skills. Often, these programs are viewed as necessary but boring. An Emergency Pursuit game was developed to provide a novel, challenging, motivating, and cost-effective teaching/learning method. The game is played by teams of nurses who compete for points by answering questions concerning emergency drugs, cardiac arrhythmias, emergency policies and procedures, and non arrest medical emergencies. Many benefits are realized from a continuing educational program using the Emergency Pursuit game. Of greatest importance is the improved proficiency and performance by nurses during clinical emergency situations. PMID- 1906482 TI - The art of contracting with speakers: an overlooked strategy. AB - In producing quality continuing education courses, contracting with and establishing rapport with speakers is as important as marketing the course itself. Presented in this article are four phases of working with speakers: initial phase, midpoint phase, course presentation phase, and post-course phase. Not only do these phases assist the continuing education program staff in developing a highly organized and well-planned program, but also they offer numerous benefits to speakers so that they can feel comfortable with all arrangements. Thus, the learning atmosphere is one in which the speaker can relax and fully enjoy the continuing education experience. PMID- 1906483 TI - The continuing education needs of diabetes nurse educators. AB - The major caveat regarding this study is the low return rate. We suspect that this is due to the extensive nature of this lengthy questionnaire. A shorter questionnaire sent at the same time to another sample drawn from the same population produced a return rate higher than 50%. However, some benefits were derived from the study. The first is the extensive set of data obtained about both the continuing education needs and the practice patterns of this sample of diabetes nurse educators. (A longer report that includes information about how the nurses spend their time, the types of diabetes education they provide, and the size and scope of the diabetes patient education programs at their institution is available from the first author.) Second, it is reasonable to assume that the nurse educators who took the time to complete this lengthy questionnaire about their continuing education needs and practices are thoughtful consumers of continuing education. Their needs and preferences should be of concern to the individuals and organizations that provide continuing education to diabetes nurse educators. In summary, the nurses in this sample are highly educated and experienced diabetes educators. They indicated a strong desire for obtaining continuing education primarily in behavioral and psychosocial issues, but perceive that they are limited by a lack of financial support and time. PMID- 1906484 TI - Continuing education needs assessment of nursing leaders in the Latvian Republic, 1990. PMID- 1906485 TI - Providing continuing education for nurses in office practice settings: an Ob-Gyn example. PMID- 1906486 TI - Antimicrobial activity of Microgard against food spoilage and pathogenic microorganisms. AB - Microgard, a commercially available fermented milk product containing antimicrobial metabolites, was a potent inhibitor for Gram-negative bacteria such as Pseudomonas, Salmonella, and Yersinia when 1% concentration was incorporated into agar media. Gram-positive Bacillus cereus, Staphylococcus aureus, and Listeria monocytogenes were insensitive to Microgard. Kluyveromyces marxianus, an unidentified black yeast, and Penicillium expansum were partially suppressed, whereas Aspergillus niger and a yogurt spoilage yeast were tolerant to 5% Microgard. Optimum activity of Microgard was at pH 5.3 and below; the concentration that gave complete inhibition depended upon the number of bacteria present as well as the genus tested. Blood agar base reversed the antagonistic activity of Microgard against Pseudomonas putida compared with plate count agar. PMID- 1906487 TI - Effects of bovine somatotropin on physiologic responses of lactating Holstein and Jersey cows during hot, humid weather. AB - Thirty-one lactating Holstein and Jersey cows were used to determine the effects of daily injections of 0 or 20 mg of recombinant bST on physiologic responses during hot, humid weather. Body temperature was determined by measuring milk temperature at each milking. Jugular blood was sampled for serum analysis of selected hormones, blood metabolites, and fatty acids, and arterial blood was sampled for blood pH and blood gas analysis. Milk was characterized for fatty acid composition. Blood pH was unchanged, but partial pressure of blood CO2, blood bicarbonate, base excess, and total CO2 declined with administration of bST. Serum triglycerides increased 89% in cows receiving bST. Blood urea nitrogen tended to decline in cows receiving bST. Serum cortisol, triiodothyronine, and thyroxine did not change, but insulin-like growth factor-1 increased 128% with bST use. Reduced milk short-chain fatty acids, increased milk long-chain fatty acids, and increased blood serum C18:1 fatty acid content occurred in cows administered bST and probably reflected tissue mobilization. Cows administered bST in hot weather had higher milk temperatures. Alterations in physiologic and metabolic measures in association with higher milk temperature suggest an interaction of bST use with hot, humid weather and reflect the need to minimize the effects of heat stress. PMID- 1906488 TI - A novel anti-ENA antibody in sera of patients with childhood idiopathic thrombocytopenic purpura. AB - Circulating antibodies against certain extractable nuclear antigens (ENA) have been shown to have diagnostic and prognostic importance in connective tissue diseases. We described here an antibody against ENA found in the sera of patients with idiopathic thrombocytopenic purpura (ITP). The antigen, tentatively called WK according to the patients' initials, was distinct from U1 RNP/Sm, SSA/SSB, Scl 70, PCNA, PM-Scl, Jo-1, and Ku by immunodiffusion. On immunoblotting, the anti-WK serum recognized polypeptides of 99 kd, 98 kd, and 96 kd in rabbit thymus extracts and a 99 kd polypeptide in KB cell extracts. The anti-WK antibody was detected in the sera of 2 out of 360 ANA positive patients, both children with clinical features of ITP. One patient developed systemic lupus erythematosus eight years after the onset of ITP. PMID- 1906489 TI - Primary and secondary detoxification in severe flecainide intoxication. AB - Since experience with primary and secondary detoxification in severe flecainide intoxications is limited, 2 different cases of flecainide intoxications are reported. In the first case, with plasma concentrations of 6500 ng/ml (therapeutic range: 200-980 ng/ml), the patient survived with a pacemaker and catecholamine support. In the second case, hemoperfusion terminated the need for emergency resuscitation during the initial phase, but was unsuccessful 3 h later. Even with a lower plasma concentration the patient died. Both patients had rapid onset of symptoms due to the very good bioavailability of the drug. Although it may be a rare intoxication, it is dangerous because of its quick onset and its efficiency in altering the cardiac stability. We recommend the prophylactic use of a pacemaker and gastric suction. The usefulness of hemoperfusion has not yet been proven. PMID- 1906490 TI - Rapid infusion of Sandoglobulin in patients with primary humoral immunodeficiency. AB - We studied 16 patients with primary disorders of humoral immunity to determine the practicality of infusing intravenous gamma globulin at rates of infusion and concentrations higher than the 4 mg/kg/min and 6% currently recommended. In the first portion of the study, the concentration of Sandoglobulin was increased from 6% to 12%. In the second portion, the flow rate was increased to 5 mg/kg/min, and if no reactions occurred, the time of each successive infusion was decreased by 10 minutes until infusions were completed in 15 to 20 minutes or vasomotor reactions occurred. Thirteen of the 16 patients completed the study; six patients achieved reaction-free rates greater than 15 mg/kg/min, and the other patients achieved rates ranging from 7.1 to 12 mg/kg/min. Seven patients had infusion times less than 30 minutes, with four patients completing infusions in 15 minutes. In the 13 patients who completed the study, there were 14 reactions in 159 infusions, mostly fever and chills, and often at the end or after the infusion. Only one infusion could not be completed because of an adverse reaction. Three patients were not able to complete the study because of adverse reactions; there were seven reactions in 11 infusions in these three patients, although none of the reactions were considered serious. Overall, in this study, most immunodeficient patients (13/16) were able to tolerate infusion rates of Sandoglobulin two to 10 times higher than the standard rates now recommended. The maximal rate of infusion must be individualized, but for carefully selected patients, infusions of 400 mg/kg can be completed in 1 hour or less.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1906491 TI - Image and role of the consultant dietitian in long-term care: results from a survey of three Midwestern States. AB - Consultant dietitians and other health care professionals in three states were surveyed to determine the image and role of consultant dietitians in long-term care. Data were derived from telephone interviews with nursing home personnel in Illinois, Indiana, and Ohio. Chi 2 Analysis was used to determine whether health professionals' perceived image and job functions of consultant dietitians were significantly different from the perceptions of consultant dietitians. Overall, respondents held positive views of consultant dietitians. More than half of the respondents said the image of consultant dietitians had improved over the past 5 years. More than half of nursing directors, dietitians, dietary managers, and medical directors responded that consultant dietitians spent adequate time in facilities to do their jobs. Results of the study indicate that consultant dietitians believe that they are viewed by other health professionals as they actually are: competent, knowledgeable, well-respected, and involved in direct patient care functions. The next challenge is for more consultant dietitians to build on this base and become proactive, developing strong franchises and more opportunities for the profession. PMID- 1906492 TI - Screening for frailty: criteria and predictors of outcomes. AB - OBJECTIVE: To determine the reliability of rapid screening by clinically derived geriatric criteria in predicting outcomes of elderly hospitalized patients. DESIGN: Prospective cohort study of 985 patients screened at the time of hospital admission and followed for 1 year with respect to the outcomes of mortality, hospital readmission, and nursing home utilization. SETTING: Palo Alto Veterans Affairs Medical Center, a tertiary care teaching hospital. SUBJECTS: Male patients 65 years of age and older admitted to the Medical and Surgical services during the period from October 1, 1985 through September 30, 1986. RESULTS: Patients were grouped by specific screening criteria into three groups of increasing frailty: Independent, Frail, and Severely Impaired. Each criterion focused on a geriatric condition and was designed to serve as a marker for frailty. Increasing frailty was significantly correlated with increasing length of hospital stay (P less than 0.0001), nursing home utilization (P less than 0.0001), and mortality (P less than 0.0001). Multivariate analyses revealed that the clinical groups were more predictive of mortality and nursing home utilization than were age or Diagnosis-Related Groups (DRGs). Rehospitalization was unrelated to age, clinical group, or DRG, suggesting that utilization may not be driven by the clinical factors measured in this study. CONCLUSIONS: Rapid clinical screening using specific geriatric criteria is effective in identifying frail older subjects at risk for mortality and nursing home utilization. Our findings suggest that geriatric syndromes are more predictive of adverse outcomes than diagnosis per se. This well operationalized screening process is inexpensive as well as effective and could easily be introduced into other hospital settings. PMID- 1906493 TI - Growth hormone in youth and old age (the old and new deja vu) PMID- 1906494 TI - Thyrotropin-releasing hormone: further extraction studies and analysis by fast protein liquid chromatography and radioimmunoassay. AB - We describe the clinical application of a radioimmunoassay combined with fast protein liquid Chromatography (FPLC) for measuring TRH immunoreactivity (TRH-IR) in blood samples extracted previously with methanol or with Sep Pak C18 cartridges. Sensitivity of the RIA was 3 fmol/tube, displacement at 50% B/B0 was achieved by 55 fmol of unlabelled TRH. Our specific antibody K2B7 (km = 2.2 fM) showed no cross reaction with other peptides. No difference was observed between the mean values of TRH-IR in 19 euthyroid, 22 hyperthyroid, 18 hypothyroid and 10 hypophysectomised patients (45 +/- 17.8, 58 +/- 30, 40 +/- 22 and 36 +/- 12 fmol/ml, mean +/- SD, respectively), whereas TRH-IR was significantly lowered (p less than 0.05) in 6 euthyroid pancreatectomised patients (21 +/- 5 fmol/ml). The reversed phase FPLC analysis of the TRH-IR presented in the methanol extracts was shown to have the same retention time as synthetic TRH. TRH could not be measured in unextracted blood samples. TRH added in preincubated (60 min, at 37 C), before extraction, blood samples showed a loss of 83.4% of immunoreactivity. Our results demonstrate that this method is able to detect TRH-IR in human blood by whole methanol extraction and/or by Sep Pak C18 cartridges extraction. Furthermore the findings suggest that the main source of circulating TRH-IR may be of extrahypothalamic (pancreatic?) origin and that the basal peripheral TRH levels are not involved or they do not clearly represent a pathological condition. PMID- 1906495 TI - The sella turcica in Sheehan's syndrome: computerized tomographic study in 54 patients. AB - A CT scan study of the sella turcica and its contents was conducted in patients with Sheehan's syndrome with a search for correlation between the radiological data and the degree of endocrine insufficiency on one hand, and the time course of the disease on the other. Fifty-four patients with Sheehan's syndrome were included: 32 with complete anterior hypopituitarism, 22 with at least one spared pituitary function. Subgroups of equal size were obtained with a cut-off of 9 years evolution. The CT scan appearance of the pituitary was never normal in Sheehan's syndrome. The sella turcica was totally empty in 39 patients. A pituitary remnant was visible in 15 patients, more frequently in those with incomplete hypopituitarism (p less than 0.005) and those with short evolution (p less than 0.025). The size of this pituitary residue never exceeded one third of the normal pituitary gland. The pituitary stalk was always visualized. On the other hand, the size of the fossa was significantly (p less than 0.001) smaller in the patients, as compared to a 12-female control group, matched for age and number of pregnancies. Among the patients there was no difference when considering the disease duration nor the degree of hypopituitarism. An empty or partially empty sella of normal or reduced size is a constant feature of Sheehan's syndrome. The presence of a pituitary remnant is inversely correlated to the duration and extension of the disease. Arachnoid herniation alone does not induce a dilatation of the fossa. PMID- 1906496 TI - A clinical evaluation of an emergency procedures training program. AB - An emergency skills training program was undertaken in a long-term care setting to increase nursing knowledge about appropriate interventions. The program incorporated readiness activities and a walk-through laboratory approach to learning. Pre- and postcourse knowledge scores revealed improvements, as did a 3 month follow-up assessment of knowledge. Most of all, the response of staff to the program was overwhelmingly positive. PMID- 1906497 TI - Hospital-acquired diarrhea in adults: a prospective case-controlled study in Mexico. AB - OBJECTIVE: To know the incidence, etiology, risk factors, morbidity, and mortality of nosocomial diarrhea in adults. DESIGN: Nested case-control study, matched by service, length of stay, date of admission, and presence of leukopenia and/or the acquired immunodeficiency syndrome (AIDS). Cases were those who developed nosocomial diarrhea. Controls were those who did not develop nosocomial diarrhea during a comparative period nor during the next ten days. Stool samples were processed in search for parasites, yeasts, bacteria, and rotavirus. SETTING: Third-level referral center, in Mexico City, Mexico, for general internal medicine and surgical problems. PATIENTS: Eligible subjects were all new admissions to the hospital from November 1987 to September 1988. Reasons for exclusion were presence of chronic diarrheal disease or melena. There were 115 cases and 111 controls. RESULTS: Overall risk of acquiring nosocomial diarrhea was 5.5%, or 1.8 episodes per 100 patient-weeks. A potential pathogen was found in 59%. Yeasts and Entamoeba histolytica were the most frequently isolated pathogens. Mortality in cases was 18%, as compared with 5% in controls (p less than .01). Multivariate analysis showed enteral feeding, recent enemas, presence of Candida species, use of antacids/H2-blockers, and presence of nasogastric tubes as significant risk factors for nosocomial diarrhea. CONCLUSIONS: Diarrhea is a common complication in hospitalized patients. It occurs more often than previously suspected and is linked with a substantial mortality. The spectrum of etiologic agents is different from that reported in pediatric hospitals. Given that nosocomial diarrhea may constitute, at least, a marker of severity of illness, it should receive more attention in general hospitals. PMID- 1906498 TI - Fluoxetine, fluvoxamine and extrapyramidal tract disorders. PMID- 1906499 TI - In vivo kinetics and characterization of IFN-gamma-producing cells during a thymus-independent immune response. AB - Using immunohistochemical techniques, we studied IFN-gamma-producing cells (IFN gamma-PC) in vivo during immune responses to thymus-independent type-2 (TI-2) Ag. Detection of IFN-gamma-PC in cryostat sections of spleen-tissue was performed with an enzyme labeled mAb directed against IFN-gamma. After TNP-Ficoll immunization, IFN-gamma-PC and TNP-specific antibody-forming cells (TNP-AFC) displayed similar kinetics reaching a maximum number at day 5 to 7. The IFN-gamma PC were localized in the same compartment as TNP-AFC and a part of them in juxtaposition to TNP-AFC. Immunization with other TI-2 Ag resulted also in a significant increase of the number of IFN-gamma-PC. In a parallel experiment we found both in vivo and in an ELISA-spot assay a significant increase of the number of IFN-gamma-PC and IFN-gamma-spot-forming-cells, respectively, in spleens of mice 6 to 7 days after TNP-Ficoll immunization. Double staining of spleen sections for IFN-gamma and surface Ag revealed that 5 to 7 days after TNP-Ficoll immunization, +/- 40% of the IFN-gamma-PC expressed the MT4 Ag (CD4), +/- 50% the Lyt-2+ Ag (CD8) and +/- 10% the asialo-GM1 Ag (NK cell). This study represents the first description of the in vivo activity and characterization of IFN-gamma PC during a TI-2 immune response. Moreover, the presented data confirm suggestions from in vitro investigations that IFN-gamma and T cells may play a direct role in the in vivo regulation of a primary immune response against a TI-2 Ag. PMID- 1906500 TI - Tumor necrosis factor production in HIV-seropositive subjects. Relationship with lung opportunistic infections and HIV expression in alveolar macrophages. AB - We have evaluated the TNF production by alveolar macrophages (AM) in 43 HIV infected subjects in relation with 1) their clinical and biologic status; 2) the presence of lung opportunistic infections (OI); and 3) the expression of HIV by AM. This production was assessed in a standard chromium release test, using monocytic U937 cells as targets. The spontaneous TNF production by AM from patients without lung OI was higher than that from seronegative controls (p less than 0.02). This production by AM was similar to that of blood monocytes, suggesting that it was not related, in these subjects, to any particular lung status. The extent of TNF release by AM was correlated to the presence of a lymphocytic alveolitis (p less than 0.05), and not to the patients' clinical presentation nor to their CD4 cell count. Finally, AM from these subjects could be normally stimulated in vitro by IFN-gamma. On the other hand, it appeared that the spontaneous TNF release by AM shown in vitro to express HIV (p24+ AM) was significantly higher than that by their p24- counterparts (p less than 0.05) and by controls (p less than 0.01). In addition, contrasting with the marked increase of TNF release by p24- AM after their stimulation with IFN-gamma (p less than 0.001), p24+ AM appeared to be refractory to any stimulation by IFN, arguing for their activation in vivo. Finally, the spontaneous TNF release by AM was significantly increased during lung OI, compared with controls (p less than 0.01) as well as with AIDS patients without OI (p less than 0.01). In addition, the production of TNF by AM in these subjects was higher than that by the corresponding blood monocytes (p less than 0.02), suggesting a compartmentalization of this response within the lungs. In conclusion, it appears that the TNF production by AM of seropositive patients is highly related to the presence of lung OI as well as to the expression of HIV by these cells. In the context of the up-regulation of HIV expression induced by TNF in vitro, our data could suggest that the in vivo release of TNF by AM could participate in viral dissemination. Moreover, we hypothesize that the generation of activated AM refractory to any further stimulation could in turn lead to the development of additional pulmonary infections. PMID- 1906501 TI - An NF-kappa B-like transcription factor mediates IL-1/TNF-alpha induction of gro in human fibroblasts. AB - Normal human foreskin fibroblasts were used to examine transcriptional induction by IL-1 and TNF-alpha of the novel cytokine gro (melanoma growth-stimulating activity). Gro mRNA was expressed at levels 100-fold above background within 45 min of exposure to either IL-1 or TNF-alpha, in growing or serum-starved cells and a similar response was shown by IL-6. In contrast, as shown previously, gro mRNA was elevated only 10-fold by serum in starved but not in growing cells, similar to fos. Thus gro expression appears to be regulated by at least two signal transduction systems: a cytokine pathway, and a growth-related pathway. Three closely related gro genes (alpha, beta, and gamma) have been described. Their proximal 5' regulatory sequences presented here show close similarity in the region to -136, which includes the NF-kappa B site at -66 to -76 in gro alpha and gro gamma, and -64 to -74 in gro beta, and sequence diversity further upstream. Transient transfection of HeLa cells with CAT constructs localized the cytokine response to a region between -84 and -65 in gro beta. Gel retardation studies with FS-2 cells identified a cytokine-induced protein binding at the NF kappa B site in all three gro genes as shown by competition studies with a pair of oligonucleotides representing wild-type and mutant sequences of the NF-kappa B binding site. Neither serum nor PMA induced a detectable gel shift at NF-kappa B or upstream to position -723. These results demonstrate conservation of the cytokine response element, NF-kappa B, in the three genes, consistent with the conservation of sequence in this region; and suggest that differential expression of the three gro genes may depend upon interactions with other sites located in the divergent upstream region. PMID- 1906502 TI - IL-10: a novel cytotoxic T cell differentiation factor. AB - A previous report concluded that a new cytokine, designated IL-10, is a growth cofactor for thymocytes, spleen, and lymph node cells. In this report, we have focused on the effects of IL-10 on CD8+ spleen T cells. We first observed that IL 10 enhances the growth of CD8+ T cells to IL-2. We then investigated the effect of murine rIL-10 on the induction of murine effector CTL from CTL precursors (CTL p) using both bulk and filler cell-free limiting-dilution cultures. IL-10 alone could not induce Con A-activated FACS-sorted CD8+ T cells either to proliferate or to generate effector CTL. In combination with IL-2, however, IL-10 augmented the cytolytic activity of effector CTL generated from Con A-activated spleen CD8+ T cells in bulk cultures incubated for 5 days. In limiting-dilution cultures (using solid-phase anti-CD3 mAb as stimulus), IL-10, in combination with IL-2, substantially increased the CTL-p frequency and augmented the cytolytic activity per clone expanded from one CD8+ T cell when compared with cells cultured in IL-2 alone. Kinetic studies showed that IL-10 is required at both early and late culture stages for optimal generation of effector CTL. The potentiating effects of IL-10 on CTL function were neutralized by an anti-IL-10 mAb. These results indicate that IL-10 has direct effects on mature T cells, and suggest that IL-10 also functions as a cytotoxic T cell differentiation factor, which promotes a higher number of IL-2-activated CTL-p to proliferate and differentiate into effector CTL. In contrast, IL-10 did not enhance significantly the lymphokine activated killer cell activity of IL-2-grown CD8+ cytotoxic T cells. PMID- 1906504 TI - Microbial aetiology of otitis externa. AB - Microbiological samples were collected from the ears of patients with otitis externa for a period of 1 year. Altogether, 226 evaluable samples from 104 males and 122 females were received. The age range of the patients was similar to that of the Norwegian population. A wide variety of bacteria and fungi was isolated. The commonest isolates, excluding normal flora, were Staphylococcus aureus (34.1%), Pseudomonas aeruginosa (22.1%) and Streptococcus pyogenes (8.8%); 9.3% samples contained fungi. Of all samples, 15% showed a mixture of Gram-positive and Gram-negative, potentially pathogenic, bacteria. Infection due to Gram negative organisms alone was commoner in males, while the lack of any obvious microbial aetiology was more frequent in females. Isolation of S. aureus together with S. pyogenes was common but that of S. aureus together with S. pyogenes was common but that of S. aureus together with P. aeruginosa was unusual. In treated patients, the finding of streptococci and S. aureus was rare whereas that of P. aeruginosa or absence of growth was common. Otitis externa involving Gram positive bacteria seems to be more prevalent in our area than in that of other reported studies. PMID- 1906503 TI - Differential regulation of the tumor suppressor molecules, retinoblastoma susceptibility gene product (Rb) and p53, during cell cycle progression of normal human T cells. AB - We have activated resting human T lymphocytes to study the roles of the putative cell cycle control gene products, retinoblastoma susceptibility gene product (Rb) and p53, in regulating cell proliferation. After stimulation with phorbol, 12,13, dibutyrate and the calcium ionophore, ionomycin, which triggers a rapid entry of cells into G1 phase, we demonstrated Rb phosphorylation 24 h later, well before the onset of DNA synthesis. This finding, in contrast to reports using proliferating cell lines, implies that Rb phosphorylation is not a proximal event regulating the G1 to S transition. The production of p53 became detectable 3 to 6 h after addition of phorbol, 12,13,-dibutyrate and ionomycin, and peaked at 30 to 42 h. To further delineate the relationship of the synthesis and metabolism of the proteins to cell cycle progression, we used three agents to arrest progression of activated T cells at various points in the cell cycle. Aphidicolin arrested the cells at the G1/S boundary, whereas deferoxamine, an iron chelator, arrested the cells at an earlier stage of the cell cycle. Cyclosporin A blocked T cell activation at the earliest point in the cell cycle. In the presence of aphidicolin, Rb phosphorylation and p53 production proceeded normally whereas cyclosporin A inhibited both events. Although deferoxamine completely prevented Rb phosphorylation, p53 production was unaffected, suggesting a differential regulation of the two molecules. Our results place Rb phosphorylation and p53 production in the hierarchy of genetic events that are thought to regulate T lymphocyte progression through the cell cycle. PMID- 1906505 TI - Bacteraemia and fungaemia in adults with cystic fibrosis. AB - The incidence of bacteraemia and fungaemia was determined in 29 adults with cystic fibrosis (CF) during 50 consecutive admissions to hospital for management of infective exacerbations of pulmonary disease. Blood was drawn for aerobic, anaerobic and fungal cultures from all patients who were febrile on admission or who became febrile during treatment. The population included eight patients who had indwelling venous access systems in situ. The overall incidence of positive blood cultures in febrile patients was 3.5% [95% confidence interval (C.I.), 1 6%]. We recorded one case of Pseudomonas aeruginosa bacteraemia and two cases of Candida albicans fungaemia. The patient with P. aeruginosa bacteraemia died 5 days after isolation of the organism from her blood. The two patients with C. albicans bacteraemia had totally implantable venous access systems (TIVAS) in situ and both recovered following appropriate therapy. These observations suggest that bacteraemia is rare in patients with CF but that there is a significant risk of fungaemia in a susceptible minority. The implications of these findings, as they relate to management of infections and care of indwelling catheters in such patients, are discussed. PMID- 1906506 TI - Endophthalmitis caused by Neisseria meningitidis. PMID- 1906507 TI - Studies of the modulation of MHC antigen and cell adhesion molecule expression on human dermal microvascular endothelial cells. AB - Interactions between leukocytes and endothelial cells, particularly in the microvasculature, are important for the initiation and regulation of tissue inflammation. These interactions are regulated by the recognition of specific cell adhesion molecules (CAM) on both leukocytes and endothelial cells. In this study, we examined the modulation of cell surface expression of MHC antigens and the CAM intercellular adhesion molecule 1 (ICAM-1), lymphocyte function antigen 3 (LFA-3), and CD44 on human dermal microvascular endothelial cells (HDMEC) both grown in monolayers and differentiated into capillary-like structures on the basement membrane-like substrate matrigel. HDMEC grown in monolayers or differentiated on matrigel express comparable cell surface MHC class I, LFA-3, CD44, and ICAM-1. ICAM-1, but not LFA-3 or CD44, was increased in expression in a dose- and time-dependent manner by interleukin 1 (IL-1) alpha, tumor necrosis factor (TNF) alpha, lipopolysaccharide (LPS), or interferon (IFN) gamma. Comparable upregulation was observed both in cells grown in monolayers and cells differentiated on matrigel. IL-1 alpha, TNF alpha, and LPS increased ICAM-1 expression on average 100-200% whereas IFN gamma was somewhat less potent. Comparative studies with human umbilical vein endothelial cells (HUVEC) demonstrated consistently lower levels of ICAM-1 expression on HUVEC, but greater increases after cytokine stimulation. Pretreatment with dexamethasone or transforming growth factor (TGF) beta did not affect baseline expression of ICAM 1 or inhibit upregulation of ICAM-1 on HDMEC by IL-1 alpha, TNF alpha, LPS, or IFN gamma. Both IFN gamma and TNF alpha, but not IL-1 alpha increased MHC class I expression, whereas only IFN gamma induced the expression of HLA-DR on HDMEC. The effect of IL-1 alpha, TNF alpha, or IFN gamma was inhibited by antibody to the specific cytokine, but was unaffected by antibody to other cytokines. Additionally, IFN alpha or beta inhibited upregulation of HLA-DR by IFN gamma, but had no effect on the increased MHC class I or ICAM-1 expression mediated by this cytokine. These data demonstrate that the expression of CAM and MHC antigens on small vessel-derived endothelial cells is different from that observed on large-vessel HUVEC, is regulated by the presence of multiple cytokines operating via distinct pathways, and the expression and regulation of these proteins appear to be similar on cells that have been grown in monolayers to those morphologically differentiated into blood vessel-like structures. PMID- 1906508 TI - Southern analysis of the 230-kD bullous pemphigoid antigen gene in normal humans, animals, and patients with junctional epidermolysis bullosa. AB - To begin to characterize the 230-kD bullous pemphigoid antigen (BPA) gene, we performed Southern analysis on genomic DNA with probes derived from 7 kb of cDNA that spans most of the coding region of this hemidesmosomal plaque protein. When hybridized to a 1-kb fragment of this BPA cDNA, normal human genomic DNA digested with EcoRI, BamHI, PstI, HindIII, or EcoRV showed only a single band, which was unique for each enzyme, indicating a single human gene for BPA. To determine if a related gene exists in animals, we used probes covering the full 7 kb of cDNA for Southern analysis of genomic DNA from various vertebrates. A related gene was detected in other mammals (monkey, cow, dog, rabbit, mouse, and rat) but not in chicken, frog, or fish. Under these same hybridization conditions a probe for human beta-actin could detect an actin gene in all these species. Furthermore, immunofluorescence showed that an antibody raised against portions of the 230-kD BPA bound to the epidermal basement membrane of mammals but not that of a bird or amphibian. Finally, because most patients with junctional epidermolysis bullosa (JEB) have defective hemidesmosomes in ultrastructure, and probably function, we analyzed genomic DNA from these patients. No restriction fragment length polymorphisms (RFLP) were detected when the DNA from 11 normals and 8 JEB patients (representing 16 possible defective genes) was digested with BamHI, EcoRI, or PstI and hybridized to any part of the cDNA. These findings indicate that 1) there is a single BPA gene in humans; 2) a closely related gene exists in other mammals but not birds, amphibia, or fish; and 3) gross abnormalities of the BPA gene are not characteristic of JEB patients. PMID- 1906509 TI - Human nidogen gene: structural and functional characterization of the 5'-flanking region. AB - Nidogen is a sulfated multifunctional glycoprotein present in basement membranes. In this study, we have cloned the 5'-flanking region of the human nidogen gene. Initially, an approximately 35-kb DNA clone (NCos4) was isolated from a human cosmid genomic library. Southern hybridization of EcoRI-digested NCos4 allowed isolation of a 3.7-kb fragment, which was shown to contain a portion of intron 1, the entire exon 1, and approximately 0.9 kb of 5'-flanking sequences of the nidogen gene. Nucleotide sequencing of the 5'-flanking DNA revealed the presence of two canonic CCAAT consensus sequences in the antisense strand and a potential variant of the TATA motif, TATTT, in the sense strand. One putative AP-2 and six putative SP1 binding sites were also present. To test the functional promoter activity of the 5'-flanking genomic DNA, two nidogen promoter/CAT reporter gene constructs, with the promoter segment spanning from -864 to -1 and from -534 to 1, respectively, were developed and analyzed in transient transfections of human and mouse cell cultures. Both constructs showed clearly detectable promoter activity, and the activity of the larger construct could be up-regulated by 12-O tetradecanoyl phorbol 13-acetate up to 2.5 times. The results indicate that the nidogen promoter/CAT gene constructs developed in this study provide a means to examine the transcriptional regulation of nidogen gene expression in human diseases of the basement membrane zone. PMID- 1906510 TI - Metabolism of arachidonic acid by human epidermal cells depends upon maturational stage. AB - Synthesis of 12- and/or 15-HETE by human epidermal cells was investigated after separating basal cells from suprabasal epidermal cell layers. We found that the main metabolite of 3H-arachidonic acid (3H-AA), formed by freshly prepared upper epidermal layers (stratum granulosum and spinosum), upon RP-HPLC co-eluted with authentic 3H-12-HETE. A 3H-15-HETE co-eluting peak selectively occurred in chromatograms obtained from supernatants of fractions containing basal cells. Supernatants of freshly prepared suspensions rich in basal keratinocytes appeared to contain 3H-15-HETE as their main 3H-AA metabolite, by far exceeding the recovered amounts of 3H-12-HETE. Moreover, keratinocytes cultured for 1 week or longer were found to produce predominantly a 3H-AA metabolite co-eluting with 3H 15-HETE. In supernatants of cultured cells, little if any 3H-12-HETE was detectable. Cultured human skin fibroblasts were not found to produce relevant amounts of HETE. Genuine tissue rich in basal cells, i.e., cells of hair follicles, were found to form twice as much 3H-15-HETE as 3H-12-HETE (3H-15 HETE/3H-12-HETE-ratio = 1.9 +/- 0.8; n = 7). Apparently, different epidermal layers are able to produce a characteristic pattern of 3H-AA metabolites. 3H-15 HETE generation seems to be a marker for proliferating keratinocytes, whereas 3H 12-HETE formation appears to be typical for differentiating suprabasal epidermal cells. Our results may explain the heretofore varying patterns of AA-metabolites by keratinocytes reported in the literature. PMID- 1906512 TI - [Influence of low level antibiotics on Pseudomonas aeruginosa]. AB - Erythromycine (EM) and chrolamphenicol (CP), the inhibitors of protein synthesis, were quantitatively examined for the growth of Pseudomonas aeruginosa EA83 and its production of extracellular proteins. The minimal inhibitory concentration (MIC) of EM for the strain was higher than 100 micrograms/ml and that of CP was 100 micrograms/ml. The growth curve of EA83 was not influenced by adding 5 micrograms/ml of EM to the broth culture, but proteolytic activity and the total protein in the culture supernate went down to 60% of the control. Number of organisms in 20 hour culture was almost constant regardless of EM concentration ranging from 0 to 50 micrograms/ml, however, the suppression of proteolytic activity and total protein in the culture supernate was seen even at 1 micrograms/ml of EM concentration. The degree of suppression was inversely proportional to EM concentration. This phenomenon was also seen in the substitution of CP for EM. All extracellular proteins separated on SDS-PAGE decreased the amount as increasing EM in the culture media. These results suggested that EM inhibited the production of not only protease including elastase, but also any other extracellular proteins including well known pathogenic factors such as exotoxin A and phospholipase C. PMID- 1906511 TI - Specific high-affinity binding of fatty acids to epidermal cytosolic proteins. AB - Cytosol from rat, mouse, and human skin or rat epidermis was incubated with [3H]arachidonic acid, [14C]retinoic acid, [14C]oleic acid, [3H]leukotriene A4, [3H]prostaglandin E2 (PGE2) or [3H] 15-hydroxyeicosatetraenoic acid (15-HETE), and protein-bound ligands were separated using Lipidex-1000 at 4 degrees C to assess the binding specificity. The binding of oleic acid and arachidonic acid with rat epidermal cytosol was rapid, saturable, and reversible. Binding of oleic acid was competed out with the simultaneous addition of other ligands and found to be in the following order: arachidonic acid greater than oleic acid greater than linoleic acid greater than lauric acid greater than leukotriene A4 greater than 15-HETE = PGE1 greater than PGE2 = PGF2. Scatchard analysis of the binding with arachidonic acid, oleic acid, and retinoic acid revealed high-affinity binding sites with the dissociation constant in the nM range. SDS-PAGE analysis of the oleic acid-bound epidermal cytosolic protein(s) revealed maximum binding at the 14.5 kDa region. The presence of the fatty acid-binding protein in epidermal cytosol and its binding to fatty acids and retinoic acid may be of significance both in the trafficking and the metabolism of fatty acids and retinoids across the skin. PMID- 1906513 TI - [The infectivity of Enterococcus faecalis in experimental urinary tract infection in mice: II]. AB - The infectivity of Enterococcus faecalis was compared with that of Escherichia coli in the urinary tract in mice. The infectivity of E. faecalis in normal mice was found to be equal to that of E. coli. The mice previously treated with cyclophosphamide, carrageenin or alloxan as the immunosuppressive drug, and restricted water supply, were more susceptible to enterococcal infection than non treated ones. These data were confirmed with histological examinations. E. faecalis is a pathogenic organism in the urinary tract and therefore cautions should be given to the treatment in clinical practice. PMID- 1906514 TI - [Chronic process with Non-A and Non-B hepatitis disseminated from the intestine (appended 500 cases followed up for two years)]. AB - At present Non-A and Non-B hepatitis disseminated from the intestine in the world is believed to have a better prognosis and has no chronicity. From 1980-1986, this hepatitis has occurred in the south of Xinjiang. It was sporadic (1980-1985) and there was an outbreak (1986). Our study indicated that the results from 500 cases followed up for two years were different from the literature reported. 1. Patients with hepatomegaly were 11.2% at 7th months, 12.8% at 19th months and 45.3% at 28th months. At the same time there were 3 cases of splenomegaly and spider in each of the 19th month and 28th month. 2. Liver function test showed that gamma-GTP, BSP and gamma-globulins rose in different degrees among the 3-7 month cases. Reexamined at 19th months, 3.6% cases of both ZTT and SGPT were high. General proteins of 8% patients dropped. In 42% of the patients the globulins rose and the album in dropped. 3. Biopsy of the liver after 28th months demonstrated that it was in agreement with the pathologic changes found in chronic lobule hepatitis of CPH under the light microscope and electron microscope. PMID- 1906515 TI - Bacillus cereus pneumonia with empyema complicating aplastic anemia--a case report. PMID- 1906516 TI - [Recent studies on mammalian lipoxygenases]. PMID- 1906517 TI - Impaired venodilatation due to nitroglycerine in patients after heart transplantation. AB - The effect of nitroglycerin on forearm peripheral vessels was assessed in three groups of patients: in patients after orthotopic heart transplantation, in patients with severe heart insufficiency and a control group. The effect on arterioles was similar in all investigated groups, the most pronounced arteriodilatation being observed in fifth minute after the application. However, the effect on veins was different. Significant venodilatation was observed only in controls, while in the other groups was not present. Thus impairment in venodilatation was revealed in both the patients after heart transplantation and in patients with severe heart failure. PMID- 1906518 TI - Essential fatty acids in plasma of patients with leprosy. AB - We have investigated the fatty-acid composition of plasma phospholipids in 61 patients with leprosy of various clinical types with either a short or long duration of treatment. All patients had significantly decreased levels of linoleic acid and alpha-linoleic acid, the parent fatty acids of the n-6 and n-3 families, respectively. Patients with a treatment duration of more than 6 months had significantly low levels of arachidonic acid and eicosapentaenoic acid compared to controls or to patients with a treatment duration of less than 6 months. There were no differences in the fatty-acid composition between multibacillary patients and paucibacillary patients. We conclude that dietary supplementation with essential fatty acids may be indicated in patients with leprosy, particularly in those with a long treatment duration. PMID- 1906519 TI - Effect of enlarged adenoids on arterial blood gases in children. AB - The enlarged adenoid is a common disorder in children resulting in nasopharyngeal obstruction. Many authors suggest that increased nasal resistance to respiration may cause disturbances in the pulmonary ventilation and carry the risk of obstructive sleep apnoea and/or cardiopulmonary syndrome. This study comprised 30 children complaining of long-standing nasal obstruction due to enlarged adenoids. Adenoidectomy was performed and the arterial blood gases were measured before and one month after surgery. Twelve normal children were also included as controls. Statistical evaluation of the results showed that O2 saturation and arterial O2 tension (PaO2) were significantly low before the operation, and increased significantly after surgery. Arterial CO2 tension (PaCO2) was insignificantly low before operation, but decreased significantly after adenoidectomy. It was concluded that enlarged adenoid may be associated with ventilatory impairment which is reversible after adenoidectomy. PMID- 1906520 TI - The feeding pharyngostomy: an alternative approach to enteral feeding. AB - We present a six-year retrospective review of feeding pharyngostomies as performed in this department. The indications, technique and complications of this procedure are discussed. PMID- 1906521 TI - Role of lipid peroxidation in the inhibition of mononuclear cell proliferation by normal lipoproteins. AB - Stimulated peripheral blood mononuclear cells (PBMC) can oxidize normal lipoproteins, and sufficiently oxidized lipoproteins are cytotoxic. However, the role of lipid peroxidation in the inhibition of mitogen-stimulated PBMC proliferation by physiologic concentrations of normal lipoproteins is unclear. In the present investigation, normal low density lipoprotein (LDL) and very low density lipoprotein (VLDL) suppressed [3H]thymidine incorporation and gamma interferon production in concanavalin A-stimulated PBMC without causing cell death. This suppression was accompanied by parallel increases in lipid peroxidation products measured as thiobarbituric acid reactive substances (TBARS). In contrast, high density lipoprotein (HDL) failed to inhibit PBMC and TBARS remains low. Differences between the PBMC suppression from LDL, VLDL, and HDL were best accounted for by normalizing the lipoprotein concentrations by their total lipid content. Moreover, the antioxidants superoxide dismutase and butylated hydroxytoluene each substantially ameliorated the inhibition of PBMC caused by LDL, and reduced the levels of lipid peroxidation products that were generated. Altogether, these results suggest that reactive oxygen species generated by stimulated PMBC may cause oxidative alterations of normal lipoproteins that may, in turn, account for much of the previously reported inhibition of PBMC by normal lipoproteins. PMID- 1906522 TI - In vivo metabolism of apolipoproteins A-IV and A-I associated with high density lipoprotein in normolipidemic subjects. AB - The kinetics of apolipoprotein A-IV associated with high density lipoproteins (HDL) of plasma from fasting human subjects was followed for 15 days in five healthy normolipidemic volunteers. Purified apoA-IV and apoA-I were radioiodinated, respectively, with 125I and 131I, incubated in vitro with normal HDL, isolated at density 1.250 g/ml, and finally reinjected intravenously as HDL 125I-labeled apoA-IV and HDL-131I-labeled apoA-I. Blood samples were withdrawn at regular intervals for 15 days, and 24-h urine samples were collected. More than 93% (93.5 +/- 0.9%) of apoA-IV was recovered in apoA-I-containing lipoprotein particles after affinity chromatography on an anti-apoA-I column and 69.7 +/- 4.8% was bound to apoA-II in apoA-I:A-II particles separated on an anti-apoA-II column. 125I-labeled apoA-IV showed a much faster decay than 131I-labeled apoA-I for the first 5 days and thereafter the curves became parallel. Urinary/plasma ratios (U/P) for the 125I-labeled parallel. Urinary/plasma ratios (U/P) for the 125I-labeled apoA-IV were much higher than those for 131I-labeled apoA-I for the first days, but the U/P curves became parallel for the last 7 days, suggesting heterogeneity of apoA-IV metabolism. A heterogeneous multicompartmental model was constructed to describe the metabolism of lipoprotein particles containing apoA IV and apoA-I and to calculate the kinetic parameters, fitting simultaneously all plasma and urine data for both tracers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1906523 TI - Evaluation of a method for study of kinetics of autologous apolipoprotein A-I. AB - Apolipoprotein A-I (apoA-I) participates in transport of plasma cholesterol. Concentrations of apoA-I depend on the balance between production and fractional clearance. To elucidate factors influencing apoA-I levels, accurate estimates of apoA-I turnover rates may be valuable. We describe a method for isolation of autologous apoA-I and its use in turnover studies. Free apoA-I was isolated from high density lipoproteins (HDL) by treatment with guanidine hydrochloride. This free apoA-I was radioiodinated with 131I and injected into eleven subjects simultaneously with HDL labeled with 125I. Plasma die-away curves of free apoA-I (131I) and HDL apoA-I (125I) were compared; fractional clearance rates averaged 0.256 +/- 0.019 (SEM) and 0.254 +/- 0.017 pools/day, respectively. Although slight differences between the two die-away curves were noted for some of the patients, the differences were relatively small; for the group as a whole, average fractional catabolic rates were not significantly different. Thus, by isolation of autologous apoA-I under the conditions described, free apoA-I seemingly provides a valid method for estimating apoA-I turnover. PMID- 1906524 TI - Comparative survey of blood thyroxine binding proteins in turtles. AB - The nature of plasma thyroxine (T4) binding activity was surveyed in turtles; binding to [125I]T4 was measured on polyacrylamide gel electrophoresis--PAGE--and on minicolumns of Sephadex G-25. An electrophoretically distinct T4 binding protein was identified in all 8 species of Pseudemys studied and in 3 other genera (Chrysemys, Deirochelys, and Emyoidea) of the same family, Emydidae. Levels of this binding activity were highly variable among individuals, but they consistently showed a similar low relative mobility (Rf) compared to albumin, and a relatively low capacity was indicated by displacement with unlabeled T4. Two emydids (Terrapene, Clemmys) showed a similar slow migrating binding peak, but binding activity was low and not as easily displaced by unlabeled T4. T4 binding to albumins was minimal in most of these emydid species, even when binding to the higher affinity, low capacity component was low or displaced by unlabeled T4 (2.5 micrograms/ml). In contrast, there was no clear evidence for a similar high affinity, low capacity binding protein in any of the other 19 species representing 13 genera of 8 families from two suborders. In these species, binding activity on Sephadex G-25 was typically low and binding on PAGE was associated largely with albumin; binding levels for albumins were highly variable. In several nonemydids (from distant lineages), binding activity on Sephadex was elevated and PAGE showed a second binding protein distinct from albumin, but it had high capacity (not readily saturable). Thus, an evolutionary divergence in T4 transport proteins is suggested within Chelonia. PMID- 1906525 TI - Toward an understanding of the epithelial requirement for osteogenesis in scleral mesenchyme of the embryonic chick. AB - Explants of scleral tissue from chick embryos of H.H. stage 29-36 (6-10 days of incubation) were used to determine if the epithelial-mesenchymal interaction which initiates scleral bone formation is cell contact, extracellular matrix, or diffusion mediated. Transfilter tissue recombinations, in which explanted interacting tissues are associated across interposing Nuclepore filters of various pore sizes and thicknesses, were performed with scleral mesenchyme and epithelium. When filters with pore sizes which would allow the passage of cell processes and diffusible substances were used, osteogenesis was initiated in the scleral mesenchyme. When cell processes were blocked with thicker filters or smaller pore sizes, bone formation still occurred, indicating that a diffusible substance mediates this tissue interaction. Further support for a diffusion mediated interaction came from transfilter experiments using dialysis membranes to discriminate the size of the molecule(s), and Millipore filters to determine the distance over which these molecules travel. These experiments revealed that the scleral epithelial diffusible factor has a molecular weight of between 3500 and 6000 daltons, and acts over distances between 150 and 300 microns. PMID- 1906526 TI - Changes induced in astrocyte cathepsin D by cytokines and leupeptin. AB - Cathepsin D is widely, but unevenly, distributed among cells and is capable of degrading a number of neural peptides and proteins. The present study was undertaken to examine the level of cathepsin D in astrocytes that might be relevant to its induction in inflammatory demyelination. Primary astrocytes were cultured from neonatal rat cerebrums according to the method of McCarthy and de Vellis. Based on staining for cell markers, cultures were greater than 95% astrocytes and less than 3% microglia. Under serum-free conditions, leupeptin induced a 1.4- to 2.0-fold increase, maximal by 48 hours, in cathepsin D protein quantified by a radioimmunoassay. Cathepsin D enzymatic activity, inhibitable by pepstatin, also increased. Northern blot analysis demonstrated that leupeptin also increased cathepsin D mRNA expression. Kinetic analysis indicated that maximal cathepsin D mRNA levels are detected 24 h after stimulation with leupeptin. Exposure of astrocytes under the same conditions to rat recombinant interferon-gamma, human recombinant tumor necrosis factor-alpha, human recombinant interleukin-1 beta, lipopolysaccharide, calcium ionophore, or a combination of these reagents did not increase the level of cathepsin D above controls. These results indicate that astrocytic cathepsin D mRNA and protein can be induced by selected materials. Furthermore, the effects attributed to leupeptin as a proteinase inhibitor may be modified by its ability to increase cathepsin D activity. PMID- 1906527 TI - Interstitial 3-methoxytyramine reflects striatal dopamine release: an in vivo microdialysis study. AB - Previous ex vivo studies have provided indirect evidence that the dopamine (DA) metabolite 3-methoxytyramine (3-MT) may be a useful index of DA release in vivo. In the present study, in vivo microdialysis was utilized to assess directly the relationship between extracellular DA and 3-MT in the striatum of rats following a variety of pharmacological manipulations. Apomorphine, a DA receptor agonist, produced a rapid, transient decrease in both DA and 3-MT. Conversely, the DA receptor antagonist haloperidol produced a concomitant increase in extracellular DA and 3-MT. Increases in DA and 3-MT were also noted following the administration of the DA uptake inhibitor, bupropion. Local application of tetrodotoxin resulted in the complete elimination of measurable amounts of DA and 3-MT in the dialysate, gamma-Butyrolactone also greatly decreased DA and 3-MT. Finally, d-amphetamine produced a large increase in DA and 3-MT in animals that had been treated previously with gamma-butyrolactone. The Pearson correlation coefficients for DA and 3-MT following these manipulations ranged from 0.87 to 0.97. These data indicate that interstitial 3-MT is an accurate index of DA release. However, when compared with previous ex vivo findings, the present results also suggest that changes in tissue concentrations of 3-MT may not reliably reflect DA release following certain pharmacological manipulations. PMID- 1906528 TI - Inhibition of glutamate release by arachidonic acid in rat cerebrocortical synaptosomes. AB - The action of arachidonic acid on glutamate release in rat cerebrocortical synaptosomes was investigated. The Ca(2+)-dependent release of glutamate evoked by 4-aminopyridine (4-AP) was inhibited by arachidonic acid (0.5-10 microM), but the KCl-evoked release was not modified. The Ca(2+)-independent release of glutamate was insensitive to low concentrations of arachidonic acid, but higher concentrations of this free fatty acid (30 microM) induced a slow efflux of cytoplasmic glutamate. The decrease in the Ca(2+)-dependent release of glutamate by arachidonic acid was consistent with a reduction in both the depolarization and the subsequent rise in the cytoplasmic free Ca2+ concentration induced by 4 AP in the nerve terminal. The inhibitory action by arachidonic acid observed in glutamate release was reversed in the presence of the K(+)-channel blocker tetraethylammonium. PMID- 1906529 TI - The effects of bronchodilator-inhaler aerosol propellants on respiratory gas monitors. AB - Spurious readings from a mass spectrometer have been reported following the administration of aerosol bronchodilators. We quantified the response of various respiratory gas analyzers to the aerosol propellant of albuterol inhalant (Proventil). The mass spectrometer systems tested, two Advantage systems, a SARA system, and a Model 6000 Ohmeda system, all displayed artifactual readings in response to the albuterol propellant. Each metered dose of the Proventil brand of albuterol contains 4 ml of Freon 11 (trichloromonofluoromethane) and 11 ml of Freon 12 (dichlorodifluoromethane). The concentration of propellant was expressed in doses/L, where each liter of gas contains 0.4 vol % of Freon 11 and 1.1 vol % of Freon 12 per dose. In proportion to the concentration of albuterol propellant, the two Advantage systems showed substantial readings of isoflurane (%) when no isoflurane was present (13% and 16% per dose/L) and reduced readings of enflurane (-8% and -10% per dose/L) and carbon dioxide (CO2) (-3 and +5 mm Hg per dose/L). The SARA system showed substantial CO2 readings when no CO2 was present (5 mm Hg per dose/L) and displayed small enflurane readings (0.1% per dose/L) when no enflurane was present. The Model 6000 unit showed CO2 readings when no CO2 was present (5 mm Hg per dose/L). Neither the Raman spectrometer, the infrared spectrometers, nor the piezoadsorptive analyzer we tested showed an artifactual effect of albuterol propellant on any of its readings. Simulation and clinical tests demonstrated that a single dose of albuterol propellant into a breathing circuit at the onset of inspiration resulted in concentrations of 0.8 and 0.3 dose/L, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1906530 TI - Laboratory evaluation of the vital signs (ICOR) piezoelectric anesthetic agent analyzer. AB - The Vital Signs (ICOR) anesthetic agent analyzer, which measures anesthetic vapor concentration by a piezoelectric crystal technique, was evaluated by using standard-calibration gases to measure the accuracy, response time, gas interference, and water vapor dependence of the analyzer. The accuracy for the measurement of vapor concentration was better than 0.08 vol%. The reproducibility of repeated measures averaged 0.003 vol%. The offsets caused by other gases were 0.02 vol% for water vapor, 0.08 vol% for 70% nitrous oxide, and less than 0.01 vol% for oxygen and carbon dioxide. Response time (10 to 90%) was 475 ms. The agent analyzer may be well suited for monitoring volatile agent concentrations during anesthesia. PMID- 1906531 TI - Accuracy of end-tidal carbon dioxide tension analyzers. AB - Substantial mean differences between arterial carbon dioxide tension (PaCO2) and end-tidal carbon dioxide tension (PETCO2) in anesthesia and intensive care settings have been demonstrated by a number of investigators. We have explored the technical causes of error in the measurement of PETCO2 that could contribute to the observed differences. In a clinical setting, the measurement of PETCO2 is accomplished with one of three types of instruments, infrared analyzers, mass spectrometers, and Raman spectrometers, whose specified accuracies are typically +/- 2, +/- 1.5, and +/- 0.5 mm Hg, respectively. We examined potential errors in PETCO2 measurement with respect to the analyzer, sampling system, environment, and instrument. Various analyzer error sources were measured, including stability, warm-up time, interference from nitrous oxide and oxygen, pressure, noise, and response time. Other error sources, including calibration, resistance in the sample catheter, pressure changes, water vapor, liquid water, and end tidal detection algorithms, were considered and are discussed. On the basis of our measurements and analysis, we estimate the magnitude of the major potential errors for an uncompensated infrared analyzer as: inaccuracy, 2 mm Hg; resolution, 0.5 mm Hg; noise, 2 mm Hg; instability (12 hours), 3 mm Hg; miscalibration, 1 mm Hg; selectivity (70% nitrous oxide), 6.5 mm Hg; selectivity (100% oxygen), -2.5 mm Hg; atmospheric pressure change, less than 1 mm Hg; airway pressure at 30 cm H2O, 2 mm Hg; positive end-expiratory pressure or continuous positive airway pressure at 20 cm H2O, 1.5 mm Hg; sampling system resistance, less than 1 mm Hg; and water vapor, 2.5 mm Hg. In addition to these errors, other systematic mistakes such as an inaccurate end-tidal detection algorithm, poor calibration technique, or liquid water contamination can lead to gross inaccuracies. In a clinical setting, unless the user is confident that all of the technical error sources have been eliminated and the physiologic factors are known, depending on PETCO2 to determine PaCO2 is not advised. PMID- 1906532 TI - A randomized double-blind study of gallium nitrate compared with etidronate for acute control of cancer-related hypercalcemia. AB - Hypercalcemia is a major source of morbidity and mortality in patients with cancer. Gallium nitrate and the bisphosphonate, etidronate, are new agents that have recently become available for treatment of this disorder. To directly compare therapeutic effectiveness, we conducted a randomized, double-blind, multicenter study of gallium nitrate compared with etidronate for acute control of cancer-related hypercalcemia. Gallium nitrate was administered by continuous intravenous (IV) infusion at a dose of 200 mg/m2/d. Etidronate was administered as a 4-hour IV infusion at a dose of 7.5 mg/kg. Both drugs were given daily for 5 consecutive days. Eligible patients had persistent moderate-to-severe hypercalcemia (total serum calcium [corrected for serum albumin] greater than or equal to 12.0 mg/dL) after 2 days of hospitalization and IV hydration. Seventy one patients were randomized and treated. Twenty-eight of 34 patients (82%) who received gallium nitrate achieved normocalcemia compared with 16 of 37 patients (43%) who received etidronate (P less than .001). Patients who received etidronate required significantly greater amounts of IV fluids (P = .04) and more hypocalcemic drug treatment (P less than .05) during the poststudy period than patients who received gallium nitrate. Kaplan-Meier analysis showed a significantly longer median duration of normocalcemia for patients treated with gallium nitrate (8 days v 0 days, P = .0005). A significantly higher proportion of patients treated with gallium nitrate developed asymptomatic hypophosphatemia compared with patients treated with etidronate (97% v 43%, P less than .001). We conclude that gallium nitrate is highly effective and superior to etidronate for acute control of moderate-to-severe cancer-related hypercalcemia. PMID- 1906533 TI - Intracisternal recombinant tissue plasminogen activator after aneurysmal subarachnoid hemorrhage. AB - Fifteen patients undergoing surgery within 48 hours of aneurysm rupture were administered recombinant tissue plasminogen activator (rt-PA) directly into the basal subarachnoid cisterns after minimal surgical clot removal and aneurysm clipping. Preoperatively, 13 patients had diffuse or localized thick subarachnoid blood clots on computerized tomography (CT), and two had diffuse thin clots. The rt-PA was given as a single intraoperative injection of 7.5 mg (one patient), 10 mg (nine patients), or 15 mg (five patients). Postoperative cisternal drainage was employed in three patients. All patients except one demonstrated partial to complete cisternal clot clearance on CT scans within 24 hours after surgery. The patient who showed no clot reduction was the only patient in this series to develop symptomatic vasospasm and was the only fatality, dying 8 days after rupture. No vasospasm was seen on follow-up cerebral angiography in six of the 14 responding patients, and mild-to-moderate arterial narrowing was seen in at least one major cerebral artery in the remaining eight patients. Severe angiographic vasospasm was not seen, although the patient who died did not undergo repeat angiography. There was one major complication early in the series which seemed clearly related to treatment, and that was a large extradural hematoma occurring within several hours of craniotomy. Intrathecal fibrinolytic treatment appears effective in clearing subarachnoid clot and reducing vasospasm, and may be associated with acceptable risks if given to patients with large-volume subarachnoid hemorrhages at high risk for severe vasospasm. PMID- 1906534 TI - Phase I trial of tissue plasminogen activator for the prevention of vasospasm in patients with aneurysmal subarachnoid hemorrhage. AB - Recent laboratory studies have demonstrated that intracisternal administration of recombinant tissue plasminogen activator (rt-PA) can facilitate the normal clearing of blood from the subarachnoid space and prevent or ameliorate delayed arterial spasm. The results of a preliminary Phase I trial of intracisternal rt PA in 10 patients are reported with documented aneurysmal subarachnoid hemorrhage (SAH). All patients enrolled were classified as clinical Grade III or IV (according to Hunt and Hess) with thick clots or layers of blood in the basal cisterns and major cerebral fissures (Fisher Grade 3). Ventriculostomy and surgery for clipping of the aneurysms were performed within 48 hours of hemorrhage. In one patient, 10 mg rt-PA was instilled into the subarachnoid cisterns prior to closing the dura. In the remaining nine patients, a small silicone catheter was left in the subarachnoid space and rt-PA (5 mg in four cases or 1.5 mg (0.5 mg every 8 hours for three infusions) in five cases) was instilled 12 to 24 hours after surgery. Minor local bleeding complications were noted in all patients receiving 5 or 10 mg rt-PA. Oozing was noted at the operative incision site in four of five patients and at the ventriculostomy site in two patients. One patient developed a small epidural hematoma that was treated by delayed drainage. No bleeding complications were noted in the patients receiving the lower regimen of rt-PA (three infusions of 0.5 mg each). Serial coagulation studies demonstrated no evidence of systemic fibrinolysis. Analysis of cisternal cerebrospinal fluid samples revealed thrombolytic tissue plasminogen activator (t-PA) levels for 24 to 48 hours. Follow-up cerebral angiography 7 to 8 days after rupture disclosed mild to moderate spasm in nine patients, while one patient with hemorrhage from a posterior inferior cerebellar artery aneurysm had severe focal spasm of the vertebral arteries that was not symptomatic. These results suggest that postoperative treatment with rt-PA may be effective in reducing the severity of delayed cerebral vasospasm. The results of serial t-PA levels suggest that the lower dosage regimen with divided dosages at 8-hour intervals is well tolerated and that even lower dosages may be effective. Further studies are clearly indicated. PMID- 1906535 TI - Effect of intrathecal fibrinolytic therapy on clot lysis and vasospasm in patients with aneurysmal subarachnoid hemorrhage. AB - A prospective series of 30 patients with a single, angiographically verified aneurysmal subarachnoid hemorrhage (SAH) was studied for the effect of intrathecal thrombolytic therapy with recombinant tissue plasminogen activator (rt-PA) on outcome, angiographic vasospasm, and computerized tomography (CT) findings after surgery. The patients included fulfilled the following criteria: operation was performed by Day 3 after the hemorrhage, CT showed only blood in the basal cisterns, and the patient had a single aneurysm or multiple aneurysms that could be treated surgically at the same operation. The patients were divided into groups of 10, with patients receiving 3, 10, or 13 mg of rt-PA in a single intracisternal injection at the end of the operation. There were no differences between the treatment groups in overall outcome. One patient from the 3-mg rt-PA group developed a postoperative intracerebral hemorrhage, and one patient from the 10-mg rt-PA group had a postoperative epidural hematoma. There was one death in the 13-mg rt-PA group that was caused by inclusion of a segment of pericallosal artery in the clip. In all treatment groups a reduction was observed in the amount of blood seen on the postoperative CT scans compared to the preoperative CT scans. The reduction in SAH grade between the 10-mg and 13-mg rt PA groups was significant (p less than 0.05). The difference in the severity of angiographic vasospasm between the 3-mg and 13-mg rt-PA groups was also significant (p less than 0.05). PMID- 1906536 TI - Nutritional knowledge of nurses in long-term health care facilities. AB - Nurses practicing in long-term care facilities were surveyed on the adequacy of their nutrition education, nutrition knowledge, and general attitudes about the diet of elderly residents. While 78% of the 95 responding nurses reported taking a required nutrition course during their training, only 61% indicated the quantity of their nutrition education was sufficient and 66% indicated the quality of their education was sufficient. The mean nutrition knowledge score was 60% correct with 51 subjects scoring at this level or less. Since the nurse is such an important caregiver for the institutionalized elderly it is recommended that more emphasis be placed upon nutrition of the elderly in the nurses' education as well as the provision of more inservice training for practicing nurses utilizing the registered dietitian. PMID- 1906537 TI - Microbial aspects of failing osseointegrated dental implants in humans. AB - The subgingival microflora of 18 failing implants were examined for pathogenic periodontal microorganisms. Peptostreptococcus micros was recovered from 6 failing implants, Wolinella recta from 6, Fusobacterium species from 5, Candida albicans from 5, and Bacteroides intermedius from 4. Enteric rods or pseudomonads constituted a significant part of the microflora in 5 failing implants. Actinobacillus actinomycetemcomitans, nonpigmented Bacteroides species, Capnocytophage species, and staphylococci were detected in a few implant failures. The present study showed that a complex microflora comprising oral as well as primarily non oral organisms, and bacteria as well as yeasts, can be associated with failing implants. This great diversity in microbial composition and antimicrobial susceptibility among "peri-implantitis" isolates suggest that antimicrobial therapies for implant failures should not be implemented without a prior comprehensive microbiological analysis. PMID- 1906538 TI - Effects of the K+ channel activators, RP 52891, cromakalim and diazoxide, on the plasma insulin level, plasma renin activity and blood pressure in rats. AB - In normo- or hyperglycemic (i.v. infusion of 50 mg/kg/min glucose over 30 min) pithed rats, diazoxide (1 mg/kg/min i.v. over 20 min) significantly reduced plasma insulin content. By contrast, cromakalim, nicorandil or RP 52891 even at doses 40-fold higher than those producing the same hypotensive effect as diazoxide in intact anesthetized normotensive rats, failed to change insulin plasma levels. Glibenclamide (0.01-0.3 mg/kg i.v.) pretreatment antagonized dose dependently the hypoinsulinemic activity of diazoxide with an i.v. ED50 value of 49 +/- 1 microgram/kg. In pithed rats, diazoxide increased markedly plasma renin activity. This effect was almost inhibited completely by 20 mg/kg i.v., but not at all by a 1-mg/kg i.v. dose of glibenclamide. In pentobarbital-anesthetized rats, diazoxide (0.5-2 mg/kg/min i.v. over 20 min) produced decreases in mean carotid artery blood pressure which were antagonized dose-dependently by glibenclamide (5-20 mg/kg i.v.). This sulfonylurea (20 mg/kg i.v.) also prevented the hypotensive effects of several i.v. administered K+ channel activators (cromakalim, RP 52891 and nicorandil) but not those of numerous hypotensive agents such as acetylcholine, adenosine, bradykinin, clonidine, histamine, salbutamol, dihydralazine, papaverine, platelet aggregating factor, nitroglycerin, nitroprusside, nitrendipine and diltiazem. Although glibenclamide lowered plasma glucose levels, its blocking activity vis-a-vis the hypotension evoked by cromakalim was not affected when its hypoglycemic effects were reversed with an i.v. injection of glucose.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1906539 TI - L-cysteine selectively potentiates nitroglycerin-induced dilation of small coronary microvessels. AB - Nitroglycerin potently dilates large coronary arteries but has minimal effect on coronary resistance vessels. Thus, nitroglycerin is not likely to be converted to vasoactive intermediates in small coronary microvessels (less than 100 microns diameter). Because nitroglycerin biotransformation may involve sulfhydryl groups, the effect of L-cysteine on the dilation caused by nitroglycerin (1 nM to 10 microM) was examined in small (80-100 microns in diameter) and large (190-300 microns in diameter) porcine coronary microvessels. Vessels were pressurized in a no-flow state and preconstricted with acetylcholine, then visualized by means of an in vitro microvessel imaging apparatus. Under control conditions, nitroglycerin caused potent dilations of large coronary microvessels, while having minimal effects on small coronary microvessels [peak relaxations 90 +/- 3 vs. 20 +/- 7% (mean +/- S.E.M.) of preconstricted diameter, respectively]. L Cysteine (100 microM) markedly enhanced relaxations of small coronary microvessels (peak relaxation 96 +/- 2%), while having no effect on relaxations of large coronary microvessels. Ethacrynic acid, which alkylates sulfhydryl groups, markedly inhibited relaxations of large coronary microvessels (peak relaxation = 31 +/- 9%) yet had a minimal effect on the small relaxations of small coronary microvessels to nitroglycerin. Thus, when sulfhydryl groups are made available, small coronary microvessels are markedly responsive to nitroglycerin. This suggests that small coronary microvessels normally lack the reductive capacity to convert nitroglycerin to its active metabolites. Prussian blue stains of sulfhydryl groups in large and small coronary microvessels were qualitatively similar. Thus, small coronary microvessels do not lack sulfhydryl groups but may be deficient in a critical pool necessary for nitroglycerin biotransformation. PMID- 1906540 TI - Spinal antinociception by adenosine analogs and morphine after intrathecal administration of the neurotoxins capsaicin, 6-hydroxydopamine and 5,7 dihydroxytryptamine. AB - The effects of intrathecal pretreatment with the neurotoxins capsaicin, 6 hydroxydopamine and 5,7-dihydroxytryptamine on spinal antinociception by adenosine analogs (NECA, 5'-N-ethylcarboxamido adenosine and CHA, N6-cyclohexyl adenosine) and morphine were examined using the rat tail flick and hot plate tests. Pretreatment with 50 micrograms capsaicin for 7 to 11 days (which reduced substance P immunoreactivity in the superficial layers of the dorsal spinal cord) produced a slight increase in the action of NECA and CHA, and reduced the action on morphine in the hot plate test but not in the tail flick test. Pretreatment with 50 to 100 micrograms 6-hydroxydopamine for 7 to 14 days (which reduced spinal cord noradrenaline levels by 54-65%) reduced spinal antinociception by NECA and CHA but not that by morphine. Pretreatment with 50 micrograms 5,7 dihydroxytryptamine (which reduced spinal cord serotonin levels by 74-89%) had no effect on any agent. Acute pretreatment with 7.5-30 micrograms phentolamine reduced the spinal antinociceptive action of noradrenaline, NECA and CHA, primarily in the hot plate test. Phentolamine (30 micrograms) also reduced the action of morphine (hot plate greater than tail flick), but did not affect the action of L-baclofen. These results suggest that spinal antinociception by adenosine analogs: 1) occurs primarily at a postsynaptic site of action (capsaicin results), and 2) is dependent on release of endogenous noradrenaline and activation of spinal adrenergic receptors (6-hydroxydopamine and phentolamine results). The reduction in the effect of morphine by capsaicin (removes a source of adenosine release) and phentolamine (antagonizes the action of endogenously released adenosine) can be explained in terms of the adenosine release hypothesis of morphine action within the spinal cord. PMID- 1906541 TI - Inhibitory effect of cyclosporine A on the activity of oral hypoglycemic agents in rats. AB - Diabetic patients often have a kidney or pancreas allograft requiring cyclosporine A (CsA) to prevent transplant rejection. These patients usually take p.o. hypoglycemic agents to control their diabetes. Because of the reported adverse effects of CsA on glucose metabolism as well as its potential use in Type II diabetics, we were interested in evaluating the in vivo effect of CsA on the activity of p.o. hypoglycemic agents. We also wanted to determine if tolbutamide produced any adverse effects on the pharmacokinetics of CsA. Male, Holtzman rats were administered CsA (p.o.) followed 1 hr later with the hypoglycemic agent. Two hours later, blood samples were obtained to determine blood glucose levels. Animals treated with CsA alone produced a significant hyperglycemia. The hypoglycemic effects produced by tolbutamide and glyburide were inhibited in animals treated concomitantly with CsA. This inhibitory effect was not observed during the first 3 hr of CsA-treatment, could not be overcome by increasing the dose of the hypoglycemic agent and occurred using small doses. CsA did not, however, interfere with the activity of exogenous NPH insulin. Tolbutamide was found to have no effect on the acute pharmacokinetics of CsA. The distribution of CsA was similar to controls in all tissues studied except the liver in which CsA levels were less in tolbutamide-treated animals. These studies demonstrate that CsA interferes with the effects of p.o. hypoglycemic agents and, therefore, blood glucose levels should be monitored closely in Type II diabetic patients taking combinations of these drugs. PMID- 1906542 TI - Rh isoimmunization complicating a triplet gestation. A case report. AB - A case occurred of Rh isoimmunization complicating a triplet gestation. Management of that extremely rare situation required careful attention to the problems inherent in both multiple pregnancy and isoimmunization. Amniocentesis and frequent antepartum fetal monitoring were the cornerstones of therapy. PMID- 1906543 TI - SDS-PAGE and immunological analysis of different axenic Blastocystis hominis strains. AB - Consistent major differences were detected by SDS-PAGE, Western blotting and Ouchterlony immunodiffusion in four axenic and microscopically indistinguishable strains of the anaerobic human parasite Blastocystis hominis from different sources. It is concluded that at least two variants with different polypeptide patterns and antigens exist and the biological significance of these findings is discussed. PMID- 1906544 TI - Purification and characterisation of toxin B from a strain of Clostridium difficile that does not produce toxin A. AB - Most toxigenic strains of Clostridium difficile produce both toxin A and toxin B. The toxin produced by C. difficile strain 8864 was characterised and compared with those produced by C. difficile strain 10463. Toxin A was not detected by immunoassay in cultures from strain 8864 and all the cytotoxic activity produced by this strain was neutralised by antiserum to toxin B. Toxin B from strain 8864 was purified and compared with toxin B from strain 10463. The size of the purified subunits of toxin B from strain 8864 differed slightly from those of strain 10463 and there were small immunological differences. The effect on fibroblast cells was more like that of C. sordellii cytotoxin than of toxin B from strain 10463. These results suggest that C. difficile strain 8864 produces a modified toxin B and does not produce toxin A. PMID- 1906545 TI - Provisional identification of Haemophilus influenzae from sputum cultures within 1 h by rapid enzyme tests. AB - Possible Haemophilus influenzae colonies in cultures of sputum samples are currently identified by tests for dependence on X and V factors. This method requires further overnight culture and may give a relatively high number of false negative results. Identification of suspected H. influenzae colonies by a 5-min test for production of indole and beta-galactosidase followed by a 1-h porphyrin test was compared with tests for dependence on X and V factors. A commercially produced form of the rapid tests (Haemstrip, Lab M, Bury, Lancs) was used to test 252 potential haemophilus colonies from cultures of sputum samples on heated blood agar. Colonies that were beta-galactosidase-positive after 5 min were considered to be non-H. influenzae and those that were beta-galactosidase negative but indole-positive were considered to be H. influenzae. At this stage the test had a sensitivity of 99.4% and a specificity of 90.9%. After 1 h, only colonies that were beta-galactosidase- and porphyrin-negative were considered to be H. influenzae, the sensitivity was then 99.5% and the specificity 100%. Similar results were found with colonies from sputum cultures on selective heated blood agar containing bacitracin. The X and V dependence and Haemstrip results were in 97.6% agreement in a double blind test. Of 100 non-haemophilus colonies tested by Haemstrip, two pseudomonads could have been identified as H. influenzae by this method. The high positive predictive value of Haemstrip results depends partly on the initial recognition of potential haemophilus colonies. PMID- 1906546 TI - Phenylketonuria and anorexia nervosa. AB - A girl with phenylketonuria and mild mental retardation developed a behaviour disorder and anorexia nervosa at the age of 14. The anorexic symptoms disappeared at the age of 20, but the behaviour disorder worsened, leading to compulsory detention in a psychiatric hospital. Serum phenylalanine levels may have influenced the course of the disorder. PMID- 1906547 TI - Hemodynamic and metabolic effects of aortic unclamping following emergency surgery for traumatic thoracic aortic tear in shunted and unshunted patients. AB - Nine cases of traumatic aortic tear treated during 1986-1987 were reviewed. Two patients had functioning Gott shunts, six patients had simple crossclamp, and one patient had a Gott shunt placed which was nonfunctional. Anesthetic management was similar in all patients. Clamp times ranged in unshunted patients from 25 to 38 minutes, and in shunted patients from 42 to 50 minutes. The crossclamp time of the patient with the nonfunctional shunt was 42 minutes. Declamping was accompanied in unshunted patients by decreases in core temperature of up to 1 degree C and acute decreases in PaO2. Marked respiratory and metabolic acidosis occurred with declamping. Respiratory acidosis resolved within 30 minutes with hyperventilation, but metabolic acidosis persisted despite bicarbonate therapy (mean = 1.2 mEq/kg) up to 6 hours after declamping. Associated elevations in serum potassium resolved as pH returned to baseline. Acid-base and electrolyte abnormalities were less marked in patients who were shunted. PMID- 1906548 TI - A triazolodiazepine platelet activating factor receptor antagonist (WEB 2086) reduces pulmonary dysfunction during endotoxin shock in swine. AB - We wanted to determine the effects of WEB 2086, a platelet activating factor (PAF) antagonist, in lipopolysaccharide (LPS) shock in anesthetized pigs. In a randomized study, LPS from S. abortus equi, 2 micrograms/kg/h was given IV for six hours. Thirteen animals received LPS and WEB 2086, 10 mg/kg/h IV for 6.5 hours, beginning 30 minutes before LPS. Eleven septic controls received saline and LPS, three nonseptic controls received saline and WEB 2086, and three nonseptic controls received saline only. In six animals we investigated the effect of synthetic PAF in doses between 50 and 10,000 ng on arterial (AP) and pulmonary arterial (PAP) pressure before and during infusion of WEB 2086. The LPS induced rise in PAP was reduced by WEB 2086 (p = 0.01) but not the decrease in AP. The LPS-induced leukopenia, hypoxia, increase in airway pressure, and release of plasminogen activator inhibitor were reduced by WEB 2086. Platelet activating factor produced an increase in PAP and a biphasic response in AP. All PAF dose response curves were shifted to the right by WEB 2086. Platelet activating factor was a pulmonary hypertensive agent and contributed to the LPS-induced respiratory alterations. PMID- 1906549 TI - The antigen of hepatitis delta virus: examination of in vitro RNA-binding specificity. AB - The only known protein of hepatitis delta virus (HDV), the delta antigen, is found both within virus particles and within the nucleus of the infected cell, where it has one or more roles essential for RNA genome replication. Others have demonstrated that the antigen has the ability, in vitro, to specifically bind HDV RNA species. We report a further examination of this phenomenon, using partially purified recombinant protein, expressed as a fusion with the staphylococcal protein A. From Northwestern (RNA-immunoblot) analyses with both complete and various subdomains of HDV genomic and antigenomic RNAs, we found that a necessary feature for specific binding was that the RNA be able to fold to some extent into the so-called rodlike structure; this structure is a predicted intramolecular partial base-pairing of the circular RNA, with about 70% of all bases involved, so as to produce an unbranched rodlike structure. Six different subregions of the HDV rodlike structure, three on the genomic RNA and three on its complement, the antigenomic RNA, were tested and found to be sufficient for antigen binding. However, features in addition to the rodlike structure may also be necessary for specific binding, because we found that a similar structure present in the RNA of the potato spindle tuber viroid did not allow binding. PMID- 1906550 TI - Characteristics of fusion of respiratory syncytial virus with HEp-2 cells as measured by R18 fluorescence dequenching assay. AB - The characteristics of fusion of respiratory syncytial virus (RSV) with HEp-2 cells were studied by the R18 fluorescence dequenching assay of membrane fusion. A gradual increase in fluorescence intensity indicative of virion-cell fusion was observed when R18-labeled RSV was incubated with HEp-2 cells. Approximately 35% dequenching of the probe fluorescence was observed in 1 h at 37 degrees C. Fusion showed a temperature dependence, with significant dequenching occurring above 18 degrees C. The dequenching was also dependent on the relative concentration of target membrane. Thus, increasing the concentration of target membrane resulted in increased levels of dequenching. In addition, viral glycoproteins were shown to be involved in this interaction, since dequenching was significantly reduced by pretreatment of labeled virus at 70 degrees C for 5 min or by trypsinization of R18-labeled virions prior to incubation with HEp-2 cells at 37 degrees C. The fusion of RSV with HEp-2 cells was unaffected over a pH range of 5.5 to 8.5, with some increase seen at lower pH values. Treatment of HEp-2 cells with ammonium chloride (20 and 10 mM), a lysosomotropic agent, during early stages of infection did not inhibit syncytium formation or progeny virion production by RSV. At the same concentrations of ammonium chloride, the production of vesicular stomatitis virus was reduced approximately 4 log10 units. These results suggest that fusion of the virus with the cell surface plasma membrane is the principal route of entry. PMID- 1906551 TI - [Reactivity of sevoflurane with carbon dioxide absorbents--comparison of soda lime and Baralyme]. AB - The reactivity of sevoflurane with carbon dioxide absorbents, soda lime and Baralyme which are commercially available carbon dioxide absorbents, was studied. A closed circuit system which was made only for this investigation was set up without rubber. Sevoflurane 5% was circulated for 17 hours. The circulated gas was analyzed by gas chromatography (GC) and degradation products were identified by a gas chromatography-mass spectroscopy (GC-MS) as fluoromethyl 2-methoxy-2, 2 difluoro-1-(trifluoromethyl) ethyl ether, fluoromethyl 2-methoxy-2-fluoro-1 (trifluoromethyl) vinyl ether, and its isomer. These degradation products of sevoflurane from soda lime and Baralyme were the same substances. The rate of degradation by soda lime was 0.88% +/- 0.306, while that by Baralyme was 3.40% +/ 0.501. Baralyme decomposed sevoflurane about four times more than soda lime. There are two possible explanations for these results. One is the Baralyme contains more potassium hydroxide than soda lime. The other is that soda lime absorbs sevoflurane more because it contains more silica. PMID- 1906552 TI - [Effect of nitroglycerin and nicardipine on ICG excretion during halothane anesthesia]. AB - We evaluated the effect of nitroglycerin and nicardipine on ICG excretion during halothane anesthesia in man. Induced hypotension with nitroglycerin during halothane anesthesia produced a significant prolongation in ICG excretion. No such significant prolongation occurred in the patients who received nicardipine. The results suggest that a reduction in hepatic blood flow during anesthesia may be much less in patients who receive halothane with nicardipine than in those who receive halothane with nitroglycerin. PMID- 1906553 TI - [Primary amyloidosis vs. PCD-associated amyloidosis]. PMID- 1906554 TI - [Amyloid (senile) plaques in Alzheimer's disease brain]. PMID- 1906555 TI - [Clinical implications of the O-antigen serovar E and drug resistance in persistent Pseudomonas infection]. AB - We studied bacteriological parameters in patients with persistent Pseudomonas aeruginosa (PA) infection, including distribution of the PA O-antigen serovars, incidence of serovar conversion during treatment and relationship between these serovars and susceptibility to antibiotics. PA was identified using an automated bacterial identification system (Avantage Microbiology Center, Abbot Lab., USA) and the PA O-antigen serovar was performed with a monoclonal serovar diagnostic kit (Mei-Assay Pseudomonas Aeruginosa, Meiji Seika, Tokyo). Antibiotic susceptibility was evaluated by minimum inhibitory concentration according to the NCCLS method. The PA was isolated in 14.7% of the total of 1,900 isolates in our hospital from April, 1987 to March, 1988, and was most frequently isolated from urine specimens (51.9%), followed by sputum (40.0%). The serovar E was isolated in 57 (36.3%) of 157 PA strains tested, followed by the serovar B (21.0%) and G (17.8%). The serovar E was widely distributed in the wards of hematology (55.6%), neurosurgery (54.2%) and urology (42.3%). The serovar E showed high resistance rates to many antibiotics: 62.5% to piperacillin; 58.3%, cefsulodin; 58.3%, cefoperazone; and 70.8%, gentamicin. Serovar conversion during treatment was noticed in 8 of 24 patients with persistent PA infection. Three of 5 patients in whom the serovar had converted to the serovar E died. These results suggest that PA infection with the serovar E, especially with that converting from another serovar is an unfavorable prognostic sign. PMID- 1906556 TI - [The role of gamma-interferon in blister formation of bullous pemphigoid]. AB - Recently it has been reported that cell-mediated immune (CMI) reaction is related to the blister formation as well as the reaction of autoantibody against the basement membrane zone (BMZ-Ab) in bullous pemphigoid (BP). Previously we reported that T-cells infiltrated were producing gamma-interferon (IFN-gamma) and that high levels of IFN-gamma were detected in the blister fluids of BP. In the present study, in order to find the effect of IFN-gamma on the skin, we have done the organ culture of normal skin explants with IFN-gamma. The dermal-epidermal separation (DES) was histologically observed in skin explants which were incubated with high level of IFN-gamma after 24 hours. The DES was found to be located between the basal layer and the site of laminin and type IV collagen. It is considered that IFN-gamma alters the antigenicity and mediates to release some other cytokines in CMI reaction. In addition to these, IFN-gamma seems to directly work on the DES in normal skin. Around the DES of the skin explants, plasminogen activator was accelerated immunohistologically. The results suggest that IFN-gamma mediated by CMI response also plays an important role as well as the autoantibody in the blister formation of BP. PMID- 1906557 TI - [Isolation of urinary heparan sulfate and chondroitin sulfate and their inhibitory activity of calcium oxalate crystal growth]. AB - Urinary heparan sulfate (U-HS) and chondroitin sulfate (U-ChS) were isolated and partially purified using two steps of anion-exchange chromatography (DE-52 and Dowex 1 x 2). Uronic acid content of these urinary glycosaminoglycans (GAGs) and commercial heparan sulfate (C-HS) and chondroitin-6-sulfate (C-C6S) was as follows; U-HS: 22.4%, U-ChS: 32.0%, C-HS: 41.6%, C-C6S: 36.0%. The inhibitory activity of these GAGs on calcium oxalate crystal growth was examined using the crystal-seed system described by Koide et al. The influence of uric acid on the inhibitory activity of the GAGs was also studied. U-HS and U-ChS exhibited nearly equal inhibitory activity to their respective commercial preparations. The inhibitory activity of U-HS was stronger than that of U-ChS. Uric acid suppressed the inhibitory activity of both, and the degree of suppression was stronger in U ChS than in U-HS. The molecular weight of the urinary GAGs was compared to that of the commercial chondroitin-6-sulfate (C6S; m.w. between 40,000 and 80,000) by gel-filtration using Sephacryl S-300HR. C6S was eluted slightly behind the void volume. U-ChS was eluted much behind C6S. Therefore, the molecular weight of U ChS was thought to be much smaller than that of C6S. U-HS was eluted into two peaks; the first one at the void volume and the second one between the peaks of C6S and U-ChS. These findings indicate the possibility that part of U-HS exists in the form of proteoglycan. PMID- 1906559 TI - [Rational use of bed capacity in surgical clinic]. AB - Surgical activity can be intensified in the presence of 3 factors: optimal full time work of surgeons, the existence of one operating table per 20 surgical beds, and financial stimulation of the entire personnel for hospital-bed turnover. Calculation of optimal full-time work of surgeons is given in illustration. PMID- 1906558 TI - [Graded hypercapnia in the postoperative evaluation of central hemodynamics in cardiosurgical patients]. AB - 117 patients were examined in the early period after operation on an open heart (aortocoronary shunt and correction of acquired valvular heart diseases). The hemodynamic values were studied by direct methods with catheterization of the right parts of the heart and pulmonary artery. The catheter was introduced into the left atrium during the operation by transseptal puncture. In the absence of the latter, pulmonary capillary wedge pressure was measured. The loading volume test (LVT) was conducted by i.v. infusion of 200-800 ml solution. Graded hypercapnia (GH) was accomplished by stepped administration of 3-5% CO2 into the inspiration line or reducing minute lung ventilation. The study revealed different sensitivity of patients to CO2 and different variants of hemodynamic changes in response to hypercapnia. The underlying factors were; (1) venoconstriction, increased return to the heart, and realization of the Frank Starling mechanism; (2) arterial vasodilation and reduced left ventricular postload; (3) increased activity of the sympathoadrenal system (revealed by indirect data--increased heart rate and myocardial contractility). The resultant effect was determined by the initial state of circulation in the patient, the contribution of each of the named mechanisms, and the ratio of the central and peripheral effects of CO2. A hypercapnic functional-diagnostic test for appraising the vascular channel volemia and functional condition of the myocardium was elaborated on basis of the obtained data and approbated clinically. It was also shown that the diagnostic significance of LVT significantly increases under conditions of GH. PMID- 1906560 TI - [Changes in hemostasis indices in patients with gastrointestinal hemorrhages depending on treatment methods]. AB - The dynamics of changes in some values of the hemostatic system was studied on days 1, 3, and 7 after gastrointestinal hemorrhage (GIH) of ulcerous etiology during enteral (administration of an electrolyte-monomer solution through a tube) and parenteral (traditional administration of infusion solutions) treatment. In operated on patients with enteral correction marked hyperfibrinogenemia was revealed, as well as diminished blood fibrinolytic activity, prolonged thrombin time, and a positive ethanol test, which indicates the predominance of hypercoagulation changes in the blood. Patients who were not subjected to operation but were given enteral correction had marked thrombocytopenia, reduced tolerance of plasma to heparin in all test periods tendency towards reduction of the fibrinogen content during the whole week after the hemorrhage in normal values of fibrinolytic activity, positive ethanol and protamine sulfate tests, which is evidence of hypocoagulation shifts in the hemostatic system. Reduction of the 4th thrombocytic factor, a tendency towards diminution of plasma tolerance to heparin, normal fibrinogen level, reduced blood fibrinolytic activity, and negative ethanol and protamine sulfate tests were revealed in patients who did not undergo operation and were given the traditional parenteral treatment, which reflects the compensatory character of the blood coagulation system response to rapidly developing blood loss. Disorders of the hemostatic system were more marked in patients with GIH who were not operated on and were given enteral correction, who require additional therapy. PMID- 1906561 TI - Kinetic analysis of amyloid fibril polymerization in vitro. AB - We investigated the polymerization kinetics of murine senile amyloid fibrils (fASSAM) in vitro. When sonicated murine senile amyloid fibrils was incubated with its constituent monomer protein, the extension of amyloid fibrils was observed in an electron microscopic analysis. Quantitative fluorometric analysis with thioflavine T (Naiki H, Higuchi K, Hosokawa M, Takeda T: Anal Biochem 177:244, 1989) revealed that (a) extension of amyloid fibrils occurred by a pseudo-first-order exponential increase in the fluorescence of thioflavine T; (b) the rate of extension was maximal around pH 7.5, and was inhibited with the increase in KCl or NaCl concentration in the reaction mixture; (c) the rate of polymerization was proportional to the product of the murine senile amyloid fibrils number concentration and the constituent monomer protein concentration; (d) the net rate of extension was the sum of the rates of polymerization and depolymerization with the equilibrium association constant K of 5 x 10(7) M-1. These results show that amyloid fibril formation can apparently be explained by a first-order kinetic model: that is, extension of amyloid fibrils proceeds by consecutive association of precursor proteins onto the ends of existing fibrils. PMID- 1906562 TI - Transcranial Doppler-estimated versus thermodilution-estimated cerebral blood flow during cardiac operations. Influence of temperature and arterial carbon dioxide tension. AB - The ability of the noninvasive continuous transcranial Doppler technique to reflect changes in cerebral blood flow during cardiac operations was evaluated in seven adults. Middle cerebral artery blood flow velocity changes were compared with simultaneous thermodilution measurements of venous blood flow in the ipsilateral internal jugular vein during 11 preset stages of the procedure. Cerebral blood flow was varied by changes in arterial carbon dioxide tension and temperature. High-dose fentanyl-droperidol anesthesia and alpha-stat pH management were employed. To facilitate comparisons between the two methods, the individual awake values of middle cerebral artery flow velocity (45.1 +/- 3.3 cm/sec, mean +/- standard error of the mean) and jugular venous blood flow (382 +/- 37 ml/min) were normalized (100%). Cerebral metabolic rate for oxygen was calculated as the product of jugular arteriovenous oxygen content difference and middle cerebral artery flow velocity or jugular venous blood flow, respectively. The individual correlations between the two flow estimates varied between 0.76 and 0.87 (median 0.83), and the correlation of the combined data from all seven patients was 0.77 (p less than 0.0001). Variations in arterial carbon dioxide tension induced significant changes in the two flow estimates both during normothermia before cardiopulmonary bypass and at deep hypothermia (20 degrees C) during cardiopulmonary bypass. The significant arterial carbon dioxide tension changes had no significant effects either on Doppler- or thermodilution-estimated cerebral metabolic rate for oxygen. Deep hypothermia (20 degrees C) reduced Doppler- and thermodilution-estimated cerebral metabolic rate for oxygen to 22.0% +/- 3.9% and 20.6% +/- 6.9% of the awake levels, respectively. The study supports the validity of using middle cerebral arterial flow velocity changes as an estimate of changes in volume flow through the brain during cardiac operations. PMID- 1906563 TI - Nocturnal nasal ventilation for treatment of patients with hypercapnic respiratory failure. AB - We reviewed the Mayo Clinic experience with nocturnal nasal ventilation (NNV) and retrospectively assessed the clinical benefits, patient compliance, and complications. NNV had been instituted in 26 patients with daytime hypercapnia and nocturnal hypoventilation due to neuromuscular diseases or chronic obstructive pulmonary disease. After initiation of NNV, 21 of 26 patients continued to use this treatment regularly (81% compliance rate) and considered their life-style improved. In this subset of patients, the arterial partial pressure of carbon dioxide during unassisted breathing decreased from 64 +/- 13 to 51 +/- 7 mm Hg, and the arterial partial pressure of oxygen increased from 58 +/- 12 to 68 +/- 8 mm Hg. No significant change was noted in the forced vital capacity or maximal respiratory pressures. Four of the five patients in whom NNV had been discontinued cited discomfort related to the mask or severity and poor prognosis of the underlying illness as reasons for cessation of treatment. We conclude that NNV is well tolerated by most patients and may improve alveolar ventilation and arterial oxygenation in patients with chronic respiratory failure. PMID- 1906564 TI - Nursing home transfers and mean length of stay in the prospective payment era. AB - Under Medicare's Prospective Payment System (PPS), hospitals have incentives to discharge Medicare patients as quickly as medically feasible, but because of shortages of nursing home beds and differential long-term care arrangements, some hospitals may encounter difficulty placing patients in nursing homes, leading to hospital backup days. This study relied on Tobit and weighted least-squares analysis to examine the determinants of hospital mean length of stay and transfer rates to skilled and intermediate care homes for selected diagnosis-related groups (DRGs) with high levels of postacute service use. Hospitals in low bed supply areas were found to have proportionately fewer nursing home transfers and longer mean lengths of stay. Having swing beds or a long-term care unit led to speedier discharges and higher skilled nursing facility (SNF) transfers, especially for patients with hip or femur procedures or major joint and limb reattachment procedures (DRGs 209 and 210). The results suggest that Medicare should consider compensating hospitals for back-up days and that bundled payment experiments could reduce current inequities resulting from differential access to nursing home care. PMID- 1906565 TI - [Parenteral nutrition versus enteral nutrition. When and why?]. PMID- 1906566 TI - [Enterococcus faecalis bacteremia. Study of 113 cases]. PMID- 1906567 TI - A multi-dimensional analysis of three chemical quantities in the blood. AB - A three-dimensional model for the analysis of the three quantities pH, pCO2 and base excess (BE), as measured in arterial blood, is presented. Whereas the conventional analysis of these quantities relies on reference regions as established from the univariate distributions, treating the quantities as uncorrelated, the present model estimates the parameters of the three-dimensional reference region from a sample of observations, based on the assumption that the observations inside the reference region follow a multi-dimensional Gaussian distribution. For observations outside the reference region, reference directions are established, corresponding to the conventionally defined specific states of acid-base disturbances. This leads to a new classification model, the results of which are compared to those of the conventional model. PMID- 1906568 TI - Mechanism of the protective action of Bay-u-3405, a new specific thromboxane receptor antagonist, in arachidonate-induced sudden death. AB - Injection of sodium arachidonate (NaAr) intravenously at a dose of 2 mg/kg is uniformly lethal in rabbits within 3 min. This sudden death is characterized by a precipitous drop in mean blood pressure within 2 min after injection of NaAr, a marked decrease in the circulating platelet count, a significant increase in intratracheal pressure and in plasma thromboxane A2 (TxA2) concentration as measured by radioimmunoassay of its stable breakdown product, TxB2. Pretreatment with Bay-u-3405, a new specific thromboxane receptor antagonist, at a dose of 1 or 10 mg/kg dramatically protected rabbits against sudden death induced by injection of NaAr. All of the rabbits treated with either of these two doses of Bay-u-3405 survived, and their thrombocytopenia, elevated plasma TxB2 concentration and bronchoconstriction were significantly attenuated. However, administration of 0.1 mg/kg Bay-u-3405 exerted no protective effect in this lethal model. Bay-u-3405 was shown to be a potent and specific inhibitor of thromboxane-mimetic induced platelet aggregation in vitro. Our data clearly show that Bay-u-3405 is a very effective protective agent against NaAr-induced sudden death in rabbits, blocking all of the known deleterious effects of TxA2. PMID- 1906569 TI - Structural measures as predictors of injury basketball players. AB - The purpose of this study was to investigate the relationship between structure and injury in basketball players, with the goal of developing equations to predict injury. We examined 45 subjects who were participating in a community center basketball league. Each subject was measured prior to the season for bilateral weight, quadricep girth, calf girth, Q-angle of the knee, dorsiflexion of the ankle, forefoot varus, rearfoot valgus, and true and apparent leg length. All lower extremity injuries causing a game to be missed were recorded during the 16-game season. Average values for bilateral weight, quadricep girth, Q-angle, rearfoot valgus, and leg length measures for the injured players were all larger than the average for the non-injured players by at least one standard deviation. A logistic regression equation using three of the variables correctly predicted the injury status of 91% of the players. The three-variable equation was then used prospectively to predict injury status for members of a small college basketball team. Only one player missed a game due to injury, and the equation identified that player as the most likely to be injured. This study demonstrates a strong relationship between structural measures and lower extremity injury in basketball players. PMID- 1906570 TI - Immunohistochemical distribution of the collagen types IV, V, VI and glycoprotein laminin in the healthy rat, marmoset (Callithrix jacchus) and human gingivae. AB - The purpose of this study was to demonstrate the localization of collagen types IV, V and VI as well as the glycoprotein laminin in biopsies of healthy rat, marmoset (Callithrix jacchus) and human gingivae. The slices, after the use of indirect immunofluorescence (incubation with antibodies against these extracellular matrix components), showed the same distribution with the anti-type IV and laminin antibodies on the basement membranes of the epithelium, blood vessels and nerves. Collagen type V, as a filamentous, and collagen type VI, as microfibrillar components, were localized in a similar pattern in the different species. In contrast to the other species, collagen type VI could not be found near the basement membranes of vessels and nerves of the marmoset gingiva. This result shows differences between human and monkey tissues, but not between rat and human gingivae, and conforms the heterogeneity of collagen type VI in the various cell and tissue types. PMID- 1906571 TI - Of snakes and bugs: nosocomial infection associated with nutritional support. PMID- 1906572 TI - Infection control of parenteral nutrition solutions. AB - Microbial contamination of parenteral nutrition solutions is a preventable cause of in patients receiving nutrition support. The components of the parenteral nutrition solutions have variable microbial growth potential. Crystalline amino acid and dextrose solutions are poor growth media for bacteria but may support fungal growth. Lipid emulsions provide an excellent medium for growth of bacteria and fungal species. Total nutrient admixtures will support microbial growth better than standard parenteral nutrition solutions will but less well than will lipid emulsion alone. Control of infection related to contaminated infusate depends on compounding procedure, quality control, appropriate storage, and procedures to prevent in-use contamination. Guidelines are presented for the preparation and administration of parenteral nutrition infusates that will minimize microbial contamination. PMID- 1906573 TI - Enteral feeding and infection in the immunocompromised patient. AB - Evidence is accumulating that immunocompromised individuals are at an increased risk of infection from foodborne pathogens including Campylobacter jejuni, Listeria monocytogenes, Salmonella spp. Normal bacterial flora and contaminants of foods and enteral feeds can also result in nosocomial infection in susceptible individuals. Safe food handling, low-microbial diets, and measures to reduce bacterial contamination of enteral foods can reduce exposure to potential pathogens in the food supply. PMID- 1906574 TI - Catheter infection control in parenteral nutrition. AB - Catheter sepsis rates related to total parenteral nutrition are variable and depend on several patient-specific factors. These factors include the presence of immunosuppression or critical illness, the use of multiple intravascular catheters, and bacterial translocation. Catheter-related sepsis may present in the patient as fever, chills, change in mental status, hypotension, and leukocytosis. In patients with suspected catheter-related infection whose peripheral blood cultures do not grow the same organism as a blood culture drawn from the catheter, a guidewire exchange of the catheter has been shown to be effective. This technique should be considered a surgical procedure. Complications that are associated with guidewire exchange of central venous catheters are catheter malposition, embolism of air or septic thrombi, and cardiac arrhythmias. PMID- 1906575 TI - Nutrition and HIV infection: a review and evaluation of the extant knowledge of the relationship between nutrition and HIV infection. Center for Food Safety and Applied Nutrition. Food and Drug Administration. PMID- 1906576 TI - Identification of amino acid residues required for Ras p21 target activation. AB - The Krev-1 gene has been shown to suppress ras-mediated transformation in vitro. Both ras and Krev-1 proteins have identical effector domains (ras residues 32 to 40), which are required for biological activity and for the interaction of Ras p21 with Ras GTPase-activating protein (GAP). In this study, five amino acid residues flanking the ras effector domain, which are not conserved with the Krev 1 protein, were shown to be required for normal protein-protein interactions and biological activity. The substitution of Krev-1 p21 residues 26, 27, 30, 31, and 45 with the corresponding amino acid residues from Ras p21 resulted in a Krev-1 protein which had ras function in both mammalian and yeast biological assays. Replacement of these residues in Ras p21 with the corresponding Krev-1 p21 amino acids resulted in ras proteins which were impaired biologically or reduced in their affinity for in vitro GAP binding. Evaluation of these mutant ras proteins have implications for Ras p21-GAP interactions in vivo. PMID- 1906577 TI - Isolation and characterization of a new mutant human cell line unresponsive to alpha and beta interferons. AB - Previously we described human cell line 2fTGH, in which expression of guanine phosphoribosyltransferase is tightly controlled by the upstream region of interferon (IFN)-stimulated human gene 6-16. After mutagenesis of 2fTGH and selection with 6-thioguanine and IFN-alpha, we isolated 11.1, a recessive mutant that does not respond to IFN-alpha. We now describe U2, a second recessive mutant, selected similarly, that complements 11.1. U2 had no response to IFN alpha or IFN-beta, and its response to IFN-gamma was partially defective. Although many genes did respond to IFN-gamma in U2, the 9-27 gene did not and the antiviral response of U2 cells to IFN-gamma was greatly reduced. Band shift assays showed that none of the transcription factors normally induced in 2fTGH cells by IFN-alpha (E and M) or IFN-gamma (G) were induced in U2. However, extracts of untreated U2 cells gave rise to a novel band that was increased by treatment with IFN-gamma but not IFN-alpha. Band shift complementation assays revealed that untreated and IFN-gamma-treated U2 cells lack the functional E gamma subunit of transcription factor E and that IFN-alpha-treated U2 cells do contain the functional E alpha subunit. PMID- 1906578 TI - A general ampC active site oligonucleotide probe for gram-negative rods. AB - We have developed a 33 mer probe that hybridizes to the serine active site of the chromosomal ampC beta-lactamase gene of Pseudomonas aeruginosa and the Enterobacteriaceae. We tested this probe against a variety of Enterobacteriaceae, and a series of 23 P. aeruginosa by dot-blots and selected Southern blots. This probe is an alternative or supplement to enzyme studies for characterizing the class of a Gram-negative rod's beta-lactamase and is a useful tool for studies of Pseudomonas beta-lactamase regulation. PMID- 1906579 TI - A search for strain differences in response of mice to mutagenesis by thio-TEPA. AB - After treatment of mice with thio-TEPA Malashenko and colleagues found differences among inbred strains in yield of dominant lethals and of chromosome aberrations in bone marrow, which they attributed to genes affecting repair. An attempt was made to confirm this work by comparing yields of dominant lethals in different strains of females mated to the same strain of males. However, no differences were found, all strain combinations giving 42-49% dominant lethals after a dose of 2 mg/kg thio-TEPA to late spermatids. Thus, the existence of genetic differences in repair of thio-TEPA induced lesions between strains CBA and C57BL/6J and between C3H/He and 101/H is not confirmed. Possible reasons for the discrepant results are discussed. PMID- 1906580 TI - Stable DNA transfection of a wide range of trypanosomatids. AB - We have shown that the Leishmania major transfection vector pR-NEO (or derivatives thereof) can be introduced and stably maintained in four species complexes of pathogenic Leishmania (L. tropica, L. mexicana, L. donovani, L. braziliensis), and the genera Endotrypanum and Crithidia; transfection of Trypanosoma cruzi or Trypanosoma brucei was not successful. Quantitative plating assays showed that the transfection efficiencies were high in L. major and Leishmania amazonensis (5x10(-5)/cell) and about 10-fold less for Leishmania panamaensis and Crithidia. Leishmania donovani transfected with pR-NEO retained the ability to infect hamsters, and amastigotes recovered after 2 months yielded G418-resistant promastigotes which retained high levels of extrachromosomal pR NEO DNA. In promastigotes, the transfected DNA existed as extrachromosomal circles, and expressed the predicted 2.4-kb hybrid NEO/DHFR-TS mRNA bearing the trans-spliced miniexon. Large quantitative differences were observed only in Crithidia: relative to transfected Leishmania species, the copy number of pR-NEO was elevated 20-fold, while the levels of the NEO/DHRFR-TS mRNA or Escherichia coli beta-galactosidase (synthesized from the expression vector pX-beta GAL) were reduced 80 and more than 1000-fold, respectively. Thus, genetic signals derived from L. major DNA that mediate RNA expression or stability are recognized by the heterologous Leishmania species but less efficiently by Crithidia. These studies suggest that pR-NEO derived vectors may be applied to the study of genes expressed throughout the life cycle in a wide range of pathogenic trypanosomatids. PMID- 1906581 TI - AIDS drugs. DDI nears approval. PMID- 1906582 TI - Further studies on the action of 5-hydroxytryptamine on lumbar motoneurones in the rat isolated spinal cord. AB - Using the hemisected spinal cord of the neonate rat, the effects of altered external Ca, thyrotrophin-releasing hormone (TRH) and a number of antagonists were tested on depolarizations evoked by 5-hydroxytryptamine (5-HT). Responses of populations of motoneurones were recorded via a ventral root. 5-Hydroxytryptamine depolarizations were not Ca-dependent but were enhanced in amplitude in Ca-free solutions. Raised Mg reversed this enhancement. 5-Hydroxytryptamine depolarizations persisted in the presence of Mn (1.5-3 mmol/l). TRH depolarized motoneurones; there was no evidence of modulation of 5-HT responses on concurrent application of TRH. Ritanserin (0.1 mumol/l) had a modest blocking action on 5 hydroxytryptamine depolarizations reducing the maximum; 1 mumol/l ritanserin caused a greater antagonism which was unsurmountable (pIC50 5.2). Ritanserin (0.1 or 1 mumol/l) did not depress responses to noradrenaline (NA). Ketanserin (0.1 mumol/l) caused a blockade of slow onset, equilibrium with the receptors requiring 1 h. Blockade by 0.01, 0.1 and 1 mumol/l ketanserin was concentration dependent (pIC50 6.2). Ketanserin 1 mumol/l, but not at lower concentrations, depressed noradrenaline responses. Mianserin (0.1 mumol/l) also caused a blockade of slow onset; 0.1 or 1 mumol/l produced a flattening of the 5-hydroxytryptamine concentration-response curve but did not depress noradrenaline responses (pIC50 4.7). The pIC50 for spiperone was 8.0. DOI (10-100 mumol/l) had no detectable agonist action but at concentrations of 0.01 and 0.1 mumol/l it acted as an antagonist. Equilibration with the receptors occurred over 2 h. DOI (0.01 mumol/l) depressed 5-hydroxytryptamine but not noradrenaline responses; higher concentrations of DOI also depressed noradrenaline responses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1906583 TI - Comparison of cromakalim-induced relaxation of potassium precontracted rabbit, cat, and rat isolated cerebral arteries. AB - The effects of cromakalim were investigated in KCl-precontracted cat, rabbit, and rat isolated cerebral arteries with intact endothelium. Potassium induced contraction of all cerebral arteries studied, but exhibited marked vessel and species variation with no spasm to 20 or 30 mmol/l KCl in the rat basilar artery or 20 mmol/l KCl in the rabbit middle cerebral artery. On sustained tension to 20 mmol/l KCl, cromakalim induced concentration-related relaxation in the rabbit basilar artery and the cat basilar and middle cerebral arteries with Hill coefficients greater than unity. Cromakalim was more potent in the rabbit basilar artery precontracted with 20 or 30 mmol/KCl than in the rabbit middle cerebral artery or the cat basilar or middle cerebral artery. Elevation of the KCl concentration to 50 mmol/l inhibited cromakalim-induced relaxation and produced a decrease in the Hill coefficient. Preincubation of cerebral arteries with glibenclamide (100 nmol/l-1 mumol/l) produced concentration-related inhibition of the cromakalim-induced relaxation in the rabbit basilar, cat basilar, and cat middle cerebral arteries precontracted with 20 mmol/l KCl. The degree of rightward shift of concentration-effect curves by glibenclamide was calculated at the EC25, EC50, and EC75 levels. A good correlation was observed between the shifts at the EC50 and EC75 levels. However, the shift in concentration-effect curves for cromakalim produced at the EC25 level was markedly less than the EC50 or EC75 levels in the presence of 1 mumol/l glibenclamide. The pA2 values for glibenclamide calculated at the EC50 level were 6.6 +/- 0.09, 7.1 +/- 0.1, and 6.5 +/- 0.5 in the rabbit basilar, cat basilar, and cat middle cerebral artery, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1906584 TI - [The effects of insulin combined with glibenclamide on glucose and lipid metabolism in patients with Type II diabetes mellitus]. AB - We compared the effects of twice-daily insulin injections (n = 22) with combined insulin-glibenclamide therapy (n = 25) on glucose and lipid metabolism in 47 type II diabetic patients (age 69 (SD 9) years, BMI 25.5 (4.8) kg/m2, diabetes duration 9 (range 1-34) years) with secondary failure to sulphonylurea. After 6 months, weight gain averaged 4.2 kg (p less than 0.05), fasting blood glucose had decreased from 14.6 to 8.5 mmol/l (p less than 0.001), HbA1c from 10.9% to 8.1% (p less than 0.001). Twenty-one patients reached HbA1c levels less than 8.0%. Patients on insulin alone injected more insulin (42 vs 26 U daily, p less than 0.01). The decrease of fasting blood glucose and HbA1c was comparable in both groups (p less than 0.001). HDL-cholesterol increased (insulin: 1.10 to 1.24 mmol/l, combined therapy: 1.03 to 1.14 mmol/l, both p less than 0.01), while plasma triglycerides and NEFA decreased (p less than 0.01). Only in patients on insulin alone did total cholesterol decrease from 7.1 to 6.3 mmol/l (p less than 0.001), and LDL-cholesterol from 4.7 to 4.1 mmol/l (p less than 0.05). Apolipoproteins AI, AII and B did not show significant changes. Almost all patients reported improved wellbeing; no severe hypoglycaemias were observed. PMID- 1906585 TI - Metabolism of 99mTc-L,L-ethyl cysteinate dimer in healthy volunteers. AB - 99mTc-L,L-Ethyl cysteinate dimer (ECD) is a brain-perfusion imaging agent, which exhibits selective retention in brain and rapid renal excretion. The pharmacokinetics and metabolism of ECD were studied in vivo in healthy humans and its metabolism in vitro was evaluated in tissue from human brain. In vitro studies showed 99mTc-L,L-ECD to be metabolized to a polar 99mTc-complex. It has been shown previously that most of the activity of 99mTc retained in the brain of the monkey in vivo is in the form of a polar 99mTc complex (Walovitch, Hill, Garrity, Cheesman, Burgess, O'Leary, Watson, Ganey, Morgan and Williams, 1989). Whole body images of the distribution of 99mTc-L,L-ECD (10 mCi i.v.) in four adult males showed good uptake in brain, with slow elimination (6.8 +/- 0.3% injected dose [mean +/- SE] at 5 min), with less than 25% decrease in activity during 4 hr of imaging. Background areas in the head and lungs washed out rapidly, providing ideal imaging conditions. Elimination of 99mTc from venous blood was biphasic, with a plateau of activity between 2-15 min (7-8% injected dose) before a terminal phase, with a t1/2 of a few hours. Organic extraction of whole venous blood showed greater than 50% of the 99mTc-L,L-ECD to be in the form of polar metabolite(s) at 5 min. They were identified in the urine as the 99mTc ethylenediylbis-L-cysteine, monoethyl ester complex (ECM) and the 99mTc ethylenediylbis-L-cysteine complex (EC). These metabolites were excreted rapidly (75% injected dose in urine within 6 hr). The results of this study support the hypothesis that the selective retention in brain, rapid blood elimination and renal excretion of 99mTc-L,L-ECD is due to its metabolic transformation to polar end products. PMID- 1906586 TI - Absence epilepsy and the level of vigilance in rats of the WAG/Rij strain. AB - In man, a relationship exists between sleep-wake states and absence epilepsy. During wakefulness, spike-wave discharges predominantly occur when the level of vigilance is not high, while during sleep they have a preference to occur during slow-wave sleep. During this latter type of sleep, spike-wave discharges prevail in periods where slow-wave sleep is light. In a series of experiments, the WAG/Rij rat model for absence epilepsy was characterized with respect to the relationships between the level of vigilance, sleep-wake states and the occurrence of spike-wave discharges. In the first experiment, continuous recordings were made for a period of 48 h and a clear circadian rhythm was established for the number of spike-wave discharges. A maximum appeared during the middle of the dark period of the rat, whereas a minimum was detected directly after the onset of the light period, the time period during which deep slow-wave sleep predominates. The relationship of spike-wave discharges with states of vigilance was elaborated in a second study. Spike-wave discharges were mainly found during light slow-wave sleep, during passive wakefulness and in transition phases from sleep to wakefulness. During REM sleep no spike-wave discharges were found. In the last three experiments, the level of alertness was enhanced by various procedures as photostimulation, a learning task and deprivation of REM sleep. In all cases, an increase of alertness decreased the amount of epilepsy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1906587 TI - 1991 cervical screening recommendations: a working group report. AB - The Department of Health and the Cancer Society invited a working group to review the 1985 recommendations on cervical screening. Minor modifications have been made to the earlier recommendations in the light of more information about the effectiveness of different screening policies, and in the expectation that comprehensive cytology registers to ensure recall and follow up of abnormalities will be in place shortly. All women from the age of 20 up to 70 years should be offered cervical screening every three years. Any woman who has never had sexual intercourse or who has had a hysterectomy with complete removal of the cervical epithelium for a benign condition need not be screened. Women should have a second smear within one year if they have never had a smear before or if more than five years have passed since their last smear. But recall through the register should not be more frequently than three yearly for women with a history of normal smears. PMID- 1906588 TI - The costs and benefits of bone marrow transplantation. AB - The average direct costs of performing a bone marrow transplant (BMT), including the subsequent year, was found to be NZ$27,074 for 43 consecutive transplants. In 29 BMTs a full two year period of follow up was available and a quality of life analysis was carried out on these patients. It was calculated that 59 quality adjusted life years (QALYs) had been gained by the BMT procedure at the time of analysis. By combining these two analyses the cost of each QALY gained by BMT is NZ$13,272. The relatively low cost of BMT is partly due to the extremely low annual costs in second and subsequent years post BMT. In our patients this cost amounted to $195 per year. The costs and benefits of BMT compare very favourably with other complex medical procedures. PMID- 1906589 TI - Cost-effective, time-efficient charting. PMID- 1906590 TI - Generating home health agency information from billing data. PMID- 1906591 TI - Nutrition: its relationship to orthopedic infections. AB - The malnutrition of orthopedic surgical patients plays an important role in the development of complications, including infection. A high index of suspicion that malnutrition exists or will soon exist in patients who are subjected to significant stress, trauma, or surgery will lead the clinician to take measures to avoid further protein calorie deficits and replenish the patient's nutritional needs. There are many pathways in which malnutrition causes a propensity for infection, and these have been discussed. Meeting the patient's nutritional needs should avoid some of the complications of infections in orthopedic surgery. PMID- 1906592 TI - Enzyme polymorphism of freshwater fish trypanosomes and its use for strain identification. AB - Sixteen strains of trypanosomes isolated from the blood of 10 freshwater fish species (all but one from South Bohemia) were characterized by enzyme analysis using disc electrophoresis in 5% polyacrylamide gel. Six enzymes were selected: ADH, LDH, MDH, ME, G6PDH and GPI. The most variable were ADH and LDH, whereas MDH, G6PDH and GPI showed the same pattern in all strains analysed. Cluster analysis indicated a very high degree of similarity among strains, even those isolated from phylogenetically distant hosts. Moreover, no correlation between enzyme pattern and host species was found. PMID- 1906593 TI - In vivo regulation of S. japonica granuloma formation by an IL-2 antagonist. AB - The present study shows an in vivo role for interleukin-2 in the formation of hepatic granulomatous inflammation in murine Schistosoma japonicum infection. Mice which had been administered an inhibitor to interleukin-2 function during acute infection were noted to have reduced cell-mediated immune responses to ConA and S. japonicum soluble egg antigen (SEA). Lymphoid tissue from these treated mice also have reduced numbers of cells which could be activated by ConA to produce interleukin-2 mRNA as shown by in situ hybridization studies. Mice with less activated lymphocytes had, on the average, a 70% reduction in the granulomatous inflammation surrounding eggs deposited in hepatic tissues of acutely infected mice. The data demonstrate that IL-2 is a key factor in the generation of granulomatous inflammation in S. japonicum infection and suggest that a potential anti-pathology vaccine could be generated based on limiting the presence of IL-2 generated during acute infection. PMID- 1906594 TI - The transition from an aerobic to an anaerobic energy metabolism in transforming Schistosoma mansoni cercariae occurs exclusively in the head. AB - It has been shown that in intact cercariae of Schistosoma mansoni in water, both head and tail had an identical, aerobic energy metabolism. As long as the environment was water, glucose was mainly degraded to carbon dioxide by both head and tail whether or not these two were still connected to each other. Transfer of intact cercariae into a simple salt medium supplemented with glucose resulted in a very rapid transition towards a more anaerobic energy metabolism: the production of lactate and pyruvate increased, whereas the production of carbon dioxide remained more or less constant. A concomitant rise in temperature to 37 degrees C was not essential for this biochemical transition, but made it more pronounced. Experiments on isolated cercarial bodies and tails in a transforming medium demonstrated that the tail oxidized glucose to carbon dioxide, whereas bodies produced mainly pyruvate and lactate. The results showed that the metabolic transition towards a more anaerobic energy metabolism occurred only in the head and not in the tail of the cercariae. Loss of the tail was shown not to be a pre-requisite for this transition, nor did it by itself trigger a metabolic switch in the resulting cercarial body. PMID- 1906595 TI - Maturation of ventilatory responses to 1-minute exercise. AB - To test the hypothesis that ventilatory responses to exercise mature during growth in healthy children, we examined CO2 production (VCO2) and minute ventilation (VE) before, during, and for 10 min after 1-min bursts of cycle ergometry exercise. Ten children (range: 7-11 y old) and 13 adults (26-42 y old) exercised at work rates corresponding to 50 and 80% of the anaerobic or lactate threshold, 50% of the difference between anaerobic threshold and maximum O2 consumption, 100% of maximum O2 consumption, and 125% of maximum O2 consumption (125% max). Gas exchange was measured breath by breath. Children recovered faster from high-intensity (above anaerobic threshold) exercise as judged by the time constant of single exponential curve-fits to postexercise VCO2 [55 +/- 10 s (1 SD) at 125%. max in children compared with 92 +/- 17 s at 125% max in adults; p less than 0.001] and VE (58 +/- 10 s at 125% max in children compared with 125 +/ 37 s in adults, p less than 0.001). Although we found no significant difference between VCO2 and VE recovery times in children, VE was significantly slower than VCO2 in adults for high-intensity exercise. Moreover, recovery times in adults increased with work intensity but were independent of them in children. Whereas the CO2 costs [calculated as total CO2 produced above baseline per unit work done (mL.J-1)] increased with work intensity in adults, no similar significant relationship was observed in children.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1906596 TI - The effect of hematocrit alterations on cerebral vascular CO2 reactivity in newborn baboons. AB - To evaluate whether baseline hematocrit affects cerebral vascular reactivity to CO2, we studied the cerebral blood flow velocity in the internal carotid artery of newborn baboons, using a pulsed Doppler technique with direct imaging. Velocity responses to varying arterial CO2 tension (PaCO2) levels were first tested under baseline hematocrit (mean +/- SD, 35.9 +/- 4.7%), after hemodilution (hematocrit 20.3 +/- 2.7%), and after hemoconcentration (hematocrit 52.7 +/- 5.2%). The data were analyzed using multiple regression models, in which blood flow velocity values were the dependent variables, and PaCO2, hematocrit, and their interaction terms (product) were the independent variables. Models for the maximum systolic velocity, time-averaged mean velocity, and the end-diastolic velocity revealed a highly significant PaCO2 effect; with each mm Hg PaCO2 increase, the velocities increased between 2.9 and 3.6% (21.8-27% per 1 kPa). PaCO2 and hematocrit interaction terms were also highly significant and inversely related to velocity (negative slopes) in the maximum systolic velocity and time averaged mean velocity models, suggesting that when the hematocrit is high, the PaCO2-induced increase in flow velocity would be attenuated, and when the hematocrit is low, such a response would be accentuated. The hematocrit effect on PaCO2 reactivity was maximal on maximum systolic velocity and least on end diastolic velocity. Systolic velocity acceleration slope was significantly reduced when the hematocrit was high, and increased when the hematocrit was low. Based on these findings, we conclude that hematocrit is an important variable affecting the rate of kinetic energy change in the large vessels, thereby influencing cerebral vascular PaCO2 reactivity as assessed in Doppler studies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1906597 TI - Prognostic factors in childhood acute encephalitis. AB - We have studied the prognostic factors in 462 children, from 1 month to 16 years old, with acute encephalitis. Death occurred in 2.8% patients, 6.7% were severely damaged and 90.5% were cured with no or only minor sequelae. The risk of death or severe damage in patients less than 1 year of age was 5.0-fold (95% confidence limits, 2.2 to 11.6; P less than 0.001) greater than that of older children. When compared with those children whose level of consciousness had been normal before admission, children who had been disoriented before admission had a 3.9-fold (1.1 to 14.3, P less than 0.05) risk and those who had been unconscious had a 25.4 fold (7.3 to 88.1, P less than 0.001) greater risk of death or severe damage. The risk of death or severe damage in patients with herpes simplex virus encephalitis was 11.7-fold (3.8 to 35.8, P less than 0.001) and in patients with Mycoplasma pneumoniae encephalitis it was 7.0-fold (2.6 to 18.7, P less than 0.001) that of other children. All patients with none of the above mentioned risk factors were cured without any major sequelae. We conclude that specific attention should be paid to the youngest patients, especially to those with an impaired level of consciousness, and all available measures should be focused on early detection of herpes simplex virus or M. pneumoniae infection. PMID- 1906598 TI - Humidifiers and other symptomatic therapy for children with respiratory tract infections. PMID- 1906599 TI - [Psychosocial problems and needs of cancer patients]. AB - A Swedish-American epidemiological study of the psychosocial problems and needs of cancer patients have shown that the personal needs of such individuals are frequently ignored. The Swedish patients requested psychological support more often than the Americans, who instead reported a need for financial assistance. Swedish patients were very rarely offered psychiatric or psychological counselling, while many Americans felt that they had received good support from physicians and other medical personnel. Fourteen per cent of the Swedes and 2.7 per cent of the American patients had no-one to whom to turn for help. The article gives concrete recommendations for better psychosocial care of cancer patients. PMID- 1906600 TI - [More people get health care with payment per treatment]. PMID- 1906601 TI - Distinctive patterns of translational reinitiation in the lac repressor mRNA: bridging of long distances by out-of-frame translation and RNA secondary structure, effects of primary sequence. AB - In the early region of the Escherichia coli lac repressor mRNA, translational reinitiation events triggered by nonsense codons occur over long distances and in a distinctive pattern not explained by simple use of the next available initiator triplet. Defined fusions of the restart sites to the lacZ coding region have been used to explore the basis for these reinitiation patterns and to ask whether the sites can function in independent initiation at the 5' end of an mRNA. The results obtained confirm earlier indications that the restart sites may have little or no inherent capacity for binding free 30S ribosomes. The data also add to growing evidence that primary sequence elements are important determinants of reinitiation efficiency. On the basis of the reinitiation activities for nonsense sites throughout the early region of the mRNA, we suggest that out-of-frame restarts and RNA secondary structure bridge long distances between the point of termination and downstream restart codons. Such bridging mechanisms could serve more generally as a means of propagating translational activity across long polycistronic mRNAs. PMID- 1906602 TI - Viral RNA annealing activities of the nucleocapsid protein of Moloney murine leukemia virus are zinc independent. AB - The zinc fingers of retroviral gag nucleocapsid proteins (NC) are required for the specific packaging of the dimeric RNA genome into virions. In vitro, NC proteins activate both dimerization of viral RNA and annealing of the replication primer tRNA onto viral RNA, two reactions necessary for the production of infectious virions. In this study the role of the zinc finger of Moloney murine leukemia virus (MoMuLV) NCp10 in RNA binding and annealing activities was investigated through modification or replacement of residues involved in zinc coordination. These alterations did not affect the ability of NCp10 to bind RNA and promote RNA annealing in vitro, despite a complete loss of zinc affinity. However mutation of two conserved lysine residues adjacent to the finger motif reduced both RNA binding and annealing activities of NCp10. These findings suggest that the complexed NC zinc finger is not directly involved in RNA-protein interactions but more probably in a zinc dependent conformation of NC protein modulating viral protein-protein interactions, essential to the process of viral RNA selection and virion assembly. Then the NC zinc finger may cooperate to select the viral RNA genome to be packaged into virions. PMID- 1906603 TI - Multiple interdependent regulatory sites in the mouse c-fos promoter determine basal level transcription: cell type-specific effects. AB - Although the induction of the mouse c-fos promoter by growth factors and specific signal transduction pathways has been analyzed in some detail, the mechanisms involved in the control of basal level transcription remain largely elusive. In this study, we present evidence for the existence of at least 9 different elements, located between the putative TATA box and position -610, that figure in basal level transcription and represent protein binding sites in different cell types. A major regulatory site in F9END, NIH3T3 and HeLa cells is the CRE around position -60. Other sites, including the SRE, a NF1 site around position -165, a novel site downstream of the SRE and three new sites upstream of the SRE play different cell type-specific roles. In addition, we have identified two regions upstream of the SRE, which seem to have cell type-specific negative regulatory effects. We also find that the precise function of several of these sites depends on the presence or absence of other elements, indicating some form of interaction between different regulatory sites. Finally, we present evidence, that the block of c-fos transcription in F9EC cells is due to the lack of transregulatory proteins, which are induced during retinoic acid mediated differentiation. PMID- 1906604 TI - Cell-type specific multiprotein complex formation over the c-fos serum response element in vivo: ternary complex formation is not required for the induction of c fos. AB - At the serum response element (SRE) of the c-fos proto-oncogene a ternary complex with two proteins, ternary complex factor (p62TCF) and serum response factor (SRF) can be formed. Its formation has previously been suggested to be necessary for efficient induction of c-fos transcription by serum in mouse NIH 3T3 fibroblasts (1) and by phorbol esters, but not by serum, in mouse BALB/c 3T3 fibroblasts (2). It is shown here by genomic dimethyl sulfate (DMS) footprinting that this ternary complex is indeed formed in NIH 3T3 cells in vivo. However, cells were found, murine F9 teratocarcinoma stem cells, in which the pattern of protection and hyperreactivity is consistent with the absence of p62TCF in the protein complex in vivo, although inducibility of the endogenous c-fos gene is not impaired. Both in NIH 3T3 cells and in F9 cells a mutated c-fos promoter that binds SRF but fails to form a ternary complex, was inducible by serum and phorbol esters to the same extent as the wild-type promoter. The data suggest that ternary complex formation is not an absolute prerequisite for the transient induction of c-fos. Ternary complex formation rather appears to enhance overall promoter efficiency. A cell type specific component determines the formation of the multicomponent transcription factor complex in vivo. PMID- 1906605 TI - Identification of a novel murine IAP-promoted placenta-expressed gene. AB - We have cloned and characterized a novel cellular gene that is promoted by an intracisternal A-particle (IAP) LTR and expressed in the mouse placenta (mouse IAP promoted placental gene, MIPP). A 1067bp cDNA clone containing an IAP LTR U5 region duplicated in its 5' terminus and an ORF coding for a potential 202 amino acids protein was isolated from an 8.5 day old mouse embryo cDNA library. Sequence analysis of the 5' region of a genomic clone revealed the presence of a solo IAP LTR with the same U5 duplication, and primer extension analysis confirmed that transcription of the MIPP gene is under the control of the IAP LTR. Expression of the MIPP gene parallels that of IAP genes in normal mouse tissues with abundant transcripts present in the placenta and also in the myeloma MOPC-315. The MIPP-encoded protein is composed of four 48-amino acid repeat units and shares homology with a vaccinia virus gene product. MIPP-related sequences were also detected in higher eukaryotic genomes including human. PMID- 1906607 TI - A set of viral DNA decamers enriched in transcription control signals. AB - We studied the frequency distribution of oligonucleotides 10 bp long in a sample of 620 Kb of viral genomes, containing 102 sequences from GenBank, with the aim of detecting transcription control signals. Two thousand three hundred decamers had a frequency 10 times higher than the mean and were subjected to further statistical analysis. For each of the 2300 decamers (parents), we counted the individual frequencies of the 30 decamers differing from the parent by one base mutation (progeny) and then calculated two variance/mean chi squares for the progeny, with and without the parent. We then studied the distribution of the ratio between the two chi squares. Out of 2300 decamers, 10 times more frequent than average, 479 decamers had a chi square ratio of 1.9 or larger. In this final set, which corresponds to less than 0.05% of all possible decamers, 58 decamers were found to contain viral and eukaryotic transcription control elements, like NF-kB, Sp1 and others. Furthermore, this set contains an excess of signals of length 5, 6, 7, 8, 9 and 10, when compared to 150 random sets, bootstrapped from the same viral genomes. PMID- 1906606 TI - The AP-1 site is required for basal expression but is not necessary for TPA response of the human stromelysin gene. AB - We have studied the activity of the AP-1 site, a target for the Fos and Jun family of transcription factors, in the context of the human stromelysin promoter (-1303 to +4). In transiently transfected human HepG2, HeLa and fibroblast cell cultures, point-mutations in any position of the stromelysin AP-1 sequence TGAGTCA (-70 to -64) reduced both the basal level and TPA-induced expression from the stromelysin promoter. TPA-induction fold of the mutant promoters, however, was comparable to that of the wild-type promoter. Similarly, antisense c-Fos mRNA expression reduced basal activity but had no significant effect on the relative TPA-response of the stromelysin promoter. Further, in mouse F9 cells cotransfected with c-Fos and c-Jun expression plasmids, the transfected wild-type stromelysin promoter activity was increased 57-fold whereas no transactivation was detected for an AP-1 mutant stromelysin promoter. In gelshift assays, stromelysin promoter fragments (-101 to -11), containing the mutated AP-1 site, all failed to bind or compete for the in vitro synthesized Fos and Jun proteins. We interpret these data to suggest that the Fos and Jun proteins, or similar activity, and the AP-1 site are required for the basal level expression of the human stromelysin gene. Strikingly, these data also suggest that the stromelysin AP-1 site is not necessary for the TPA-response. PMID- 1906608 TI - An Alu polymorphism intragenic to the neurofibromatosis type 1 gene (NF1). PMID- 1906609 TI - Smile, it'll never happen. PMID- 1906610 TI - Misoprostol does not alter the pharmacokinetics of propranolol. AB - Twelve healthy volunteers took part in a randomised, double-blind, balanced, cross-over study to investigate the effect of misoprostol on the pharmacokinetics of propranolol. The subjects took propranolol 80 mg twice daily by mouth plus either misoprostol 400 micrograms twice daily or placebo by mouth for 14.5 days, followed by a 2-week washout period, followed by the alternate treatment for 14.5 days. Misoprostol had no significant effect on the t/2, Cmax or AUC of propranolol either after a single dose or at steady state. PMID- 1906611 TI - Testicular teratoma and peripheral neurofibromatosis. PMID- 1906612 TI - Hydrogen peroxide as an alternative hatching egg disinfectant. AB - The present study examined the effectiveness of H2O2 at different concentrations to disinfect broiler hatching eggshell surfaces and to maintain hatching potential. Under pure culture conditions, .50% H2O2 yielded over a 6 log kill in 30 s of three potential eggshell bacterial contaminants. Under higher H2O2 demands, such as occurs on eggshell surfaces, H2O2 concentrations of 5% (vol/vol) were required to disinfect the shell surfaces (approximately 5 log reduction). Hatchability of fertile eggs from a 44-wk-old flock was significantly increased by 2% following spraying 5% H2O2 in comparison to untreated controls. Level of contaminated eggs and "early-dead" embryos were significantly reduced in the H2O2 treated eggs. In comparison with formaldehyde fumigation, no significant difference in hatchability due to H2O2 treatment was detected in eggs from a 30- or 56-wk-old flock. Eggshell permeability, as measured by egg moisture loss in an incubator, was not significantly affected by H2O2 (5%) or formaldehyde fumigation when compared with untreated or water-sprayed control eggs. These results demonstrated that H2O2 compared favorably to formaldehyde as a hatching egg disinfectant without adversely affecting hatching potential. Under some conditions, H2O2 actually improved the hatching potential of fertile broiler eggs compared with hatchability of untreated eggs. PMID- 1906613 TI - Effects of dietary amino acid levels on performance and carcass composition of broilers 42 to 49 days of age. AB - Broilers were grown to 42 days on nutritionally complete diets. From 42 to 49 days in two trials, broilers were fed diets formulated to contain 70, 80, 90, 100, 110, or 120% of recommended amino acid (AA) values. In four additional trials, the same AA levels were fed; in addition, Met and Lys were added to diets formulated to contain 70, 80, and 90% to equal levels of the 110% AA diet. Body weight gain (BWG), feed consumption (FC), feed conversion (FCR), dressing percentage (DP), and abdominal fat (AF) were measured. From 42 to 49 days, dietary AA levels had little effect on BWG, DP, or AF of female broilers. When male broilers were fed diets containing less than 100% of the recommended AA levels, BWG was reduced and AF increased. Broiler FC increased and FCR decreased as the AA level of the diet decreased. The addition of Met and Lys to the 90% AA diet improved performance; however, the addition of Met and Lys to the 70% AA diet had no beneficial effect. Amino acid levels may be reduced in broilers diets fed from 42 to 49 days; however, male broilers are more sensitive than females to reductions in AA levels during this period. PMID- 1906614 TI - Care of the patient with MS. PMID- 1906615 TI - Management of gout. PMID- 1906617 TI - [The clinical value of Mycobacterium tuberculosis with different biological properties]. AB - The main biological properties (including viability, drug resistance and virulence) of Mycobacterium tuberculosis, identified in 180 newly-diagnosed patients with different forms of destructive pulmonary tuberculosis and living in Leningrad, North-Western and Extreme Northern regions, were studied as compared with those identified in 40 patients with chronic destructive pulmonary tuberculosis. The viability of M. tuberculosis by their growth and mass increase rates has a prognostic importance and should be taken into account in choosing an appropriate chemotherapy. The use of a standard method of absolute concentrations to determine the M. tuberculosis drug resistance is quite sufficient in clinical practice to introduce corrections into antituberculous chemotherapy. No correlation between M. tuberculosis virulence, and the course of tuberculous process and its treatment efficacy was found. PMID- 1906616 TI - Spirulina as a source of vitamin A. AB - Experiments were carried out to assess spirulina fusiformis-a blue green algae as a source of vitamin A in rats. In one experiment, the control rats were fed synthetic vitamin A and the experimental rats spirulina as the sole source of vitamin A. The liver vitamin A concentration of spirulina-fed rats of both sexes was found to be significantly higher than that of the control rats. In another experiment the absorption of carotenes from the solvent extract of spirulina and their availability (vitamin A value) as judged by the levels of vitamin A and carotene in plasma and liver were compared with those of synthetic beta-carotene or vitamin A in male rats. The absorption of beta-carotene from spirulina extract tended to be lower than that of crystalline beta-carotene at doses of 550 and 1100 micrograms of beta-carotene. The difference became insignificant at lower beta-carotene dose of 275 micrograms. Spirulina carotene-fed rats did not show a strict dose related increase in the liver or serum vitamin A concentration. The liver vitamin A storage and plasma levels of vitamin A of spirulina carotene-fed rats was much higher than expected. The results of the two studies reported suggest that the algae spirulina can be a valuable source of vitamin A. PMID- 1906618 TI - [The effect of an ozone-oxygen mixture on Mycobacterium tuberculosis and conditionally pathogenic microorganisms]. AB - The impact of a gaseous ozone-oxygen mixture (OOM) on Mycobacterium tuberculosis (MBT) and opportunistic microorganisms was studied. It was demonstrated that on 15- and 30-min exposure, OOM caused a significant decrease in the number of colonies of the grown microorganisms as compared with the control. The OOM mixture produced the highest effect of the MBT suspension, which is likely to be related to a greater surface of ozone contact with a cell than with a dense medium, and higher concentration of ozone and its highly active radicals that arise from a treatment process. After treatment with a gaseous mixture, 80-90% of the microbial cells lost their reproductive ability. The strains grown after OOM action retain drug sensitivity of the original strain. The results suggest that the use of a gaseous OOM mixture is promising in the treatment of tuberculosis to cleanse the destruction cavities and pleural empyemas, including those of nonspecific etiology. PMID- 1906619 TI - Inhibition of rabbit erythroid 15-lipoxygenase and sheep vesicular gland prostaglandin H synthase by gallic esters. AB - Gallic acid esters possessing a varying chain length of their alcohol moiety were tested for their inhibitory potencies on 15-lipoxygenase from rabbit reticulocytes and prostaglandin H synthase from sheep vesicular glands. Octyl gallate and decyl gallate proved to be the most powerful inhibitors of both enzymes showing concentrations of half-inhibition of about 0.25 mumol/l for the reticulocyte lipoxygenase and of about 25 mumol/l for the prostaglandin H synthase. PMID- 1906620 TI - [Trends in the development of lipoxygenase inhibitors]. PMID- 1906621 TI - Adaptive cytoprotection against alcohol injury in the rat stomach is not due to increased prostanoid synthesis. AB - This study evaluated the effects of 25% ethanol, a mild irritant, on endogenous prostanoid synthesis in the rat stomach before and after exposure to oral 100% ethanol. Rats received water or 25% ethanol orally. After 15 min, a portion of each group was sacrificed and the remaining animals treated with 100% ethanol prior to sacrifice one minute later. Microsomal membrane fractions were prepared from the glandular gastric mucosa in all groups and incubated with 14C arachidonic acid in the presence of cofactors. Endogenous mucosal prostanoid synthesis was analyzed by radiochromatography and results correlated with the presence or absence of gastric injury macroscopically. Prostanoids measured included PGI2, PGF2 alpha, PGE2, PGD2, PGA2, and thromboxane A2. Additional experiments were performed in like manner to those just described with the exception that indomethacin (5 mg/kg intraperitoneally) pretreatment was rendered. Stomachs exposed to water or 25% ethanol alone demonstrated a modest and equivalent level of synthesis of all prostanoids measured. Exposure to 100% ethanol (with and without mild irritant pretreatment) significantly increased prostanoid synthesis (especially PGI2, PGF2 alpha, and PGE2) compared with stomachs exposed to water or 25% ethanol alone; only mild irritant treated mucosa was protected from injury by 100% ethanol. Indomethacin pretreatment reversed the increased prostanoid synthesis in mucosa exposed to 100% ethanol, with or without mild irritant pretreatment, and partially reversed the protective effect of 25% ethanol. Other experiments using tissue slices in which perturbations in mucosal levels of prostanoids were measured by radioimmunoassay under identical experimental conditions exhibited similar results. These data dispute the notion that adaptive cytoprotection is mediated by increased endogenous prostanoid synthesis. The partial reversal of this process by indomethacin was most likely secondary to some other action of this agent, such as a reduction in gastric blood flow, rather than direct effects on prostanoid synthesis. PMID- 1906622 TI - Isoproterenol activation of prostaglandin production in guinea-pig airway muscle preparations from immature and mature animals. AB - The aim of this study was to evaluate the capacity of isoproterenol to activate the cyclooxygenase pathway in tracheal and bronchial tissues derived from immature (198 +/- 4 g, N = 12) and mature (997 +/- 28 g, N = 12) guinea-pigs. Immunoreactive PGE2 and PGF2 alpha were measured in bath samples obtained during resting tone and when tissues had been maximally contracted or relaxed. Results from these experiments showed that histamine contractions were significantly greater in tracheal than in bronchial preparations, an effect which was independent of age. Isoproterenol and theophylline were equiactive in relaxing basal tone of tracheal and bronchial tissues when data for each tissue type was compared with results in the different age groups. This effect was also independent of age. When results were normalized for tissue wet weights, the quantities of prostaglandins produced in tissues from mature guinea-pigs were less than those generated in similar tissues derived from immature animals. These data indicate significant modifications in basal prostaglandin production in tissues from immature and mature guinea-pigs. In addition, isoproterenol stimulated prostaglandin production in airways from immature and mature animals whereas theophylline did not alter the basal production. PMID- 1906623 TI - The influence of socio-economic status on prognosis of patients with cancer of the tongue after radiotherapy. PMID- 1906624 TI - Treatment response on CT scan in patients with brain metastases treated with irradiation. AB - To evaluate the role of CT scans in the assessment of response to therapeutic irradiation of brain metastases, CT findings of 64 patients were reviewed retrospectively. Enhanced tumor on CT scans disappeared in 21 patients, who survived significantly longer than those whose CT scans showed less than 50% regression (p less than 0.01). Ring contrast enhancement (ring CE) of the tumor on pre-RT CT scan did not seem to affect the patient's prognosis for survival. Tumors with ring-CE on pre- and post-RT CT scans, however, did not regress as much as those without ring-CE. Patients without ring-CE on pre- and post-RT CT scans tended to survive longer than those with ring-CE. This study suggests that tumor regression and the CE pattern on pre- and post-RT CT scans would be useful prognostic indicators for patients with brain metastases. PMID- 1906625 TI - Follow-up by 31P NMR spectroscopy of the energy metabolism of malignant tumor in rats during treatment. AB - The energy metabolism of tumors in rats was investigated by in vivo 31P-NMR spectroscopy. The effects of radiotherapy, chemotherapy or radiotherapy combined with 5-fluorouracil (5-FU) chemotherapy were evaluated by observing the changes of these spectra in chemically induced subcutaneous fibrosarcoma in rats. Two milligrams of DMBA in solution in olive oil were administered subcutaneously in the flank of 20 Wistar rats and 17 fibrosarcoma occurred. 31P NMR spectra were recorded with a Bruker Medspec 30/47 spectrometer using a surface coil positioned over the tumor. We did not observe significant changes in the spectra during tumor growth. Radiotherapy and 5-FU chemotherapy alone did not induce major changes in the 31P spectra. But the situation was completely different for animals receiving the therapeutic combination. A clear increase in the ratio of inorganic phosphate to total phosphorus signal was observed 48 h after the first irradiation session. The pH shifted concurrently to the acidic range. No effect on tumor regression was observed in the rats from the chemotherapy group, while regression was less than 50% in rats treated by irradiation only, and at least 80% in the combined group. PMID- 1906626 TI - [An evaluation of the sterilizing activity of paraformaldehyde]. AB - Sporocidal activity of paraformaldehyde tablets was assessed by means of the Association of Official Analytical Chemists technic which is required in Brazil to register this class of sanitizing substances by the Health Ministery. According to this methodology paraformaldehyde showed sterilizing activity at the 3% (3.0 g/cm3) concentration in 3 hour exposure period at 50 degrees C in the presence of relative humidity. PMID- 1906627 TI - [Congenital cardiac diverticulum originating from both ventricles]. AB - Congenital cardiac diverticuli are infrequent. More so, if one is specially restrictive with the criteria. Usually, they are not isolated but a part of a malformation syndrome that affects the medium thoraco-abdominal line and have an embryological explanation. We present a case of congenital cardiac diverticulum originating from both ventricles with a thoraco-abdominal malformation. We describe the clinical findings, the nuclear magnetic resonance, the echocardiography and cardiac catheterization. We comment the anatomy, the total diagnosis, therapy and complications. PMID- 1906629 TI - The effects of catecholamines on ventilation in rainbow trout during hypoxia or hypercapnia. AB - This study assessed the effects of experimentally elevated plasma catecholamine levels on gill ventilation in rainbow trout (Oncorhyncus mykiss) exposed to various external ventilatory stimulants. Trout were exposed to hypoxia (water PO2 (PwO2) = 90 Torr) or hypercapnia (water PCO2 (PwCO2) = 4.5 Torr) for 30 min. These conditions caused gill ventilation volume (Vw) to increase by 2.3- and 1.5 fold, respectively, but did not stimulate release of catecholamines into the blood. While the stimulus (hypoxia or hypercapnia) was maintained, fish were given a bolus injection (0.3 ml), followed by intra-arterial infusion (0.6 ml.h 1), of a catecholamine mixture (2 x 10(-5) mol.l-1 adrenaline + 5 x 10(-6) mol.l 1 noradrenaline) to mimic the physiological concentrations and ratios of these catecholamines observed under more severe hypoxic or hypercapnic conditions. In hypoxic fish, this treatment caused a significant, but transient (5 min) depression of ventilation while during hypercapnia, the administration of exogenous catecholamines caused a more prolonged hypoventilatory response. These hypoventilatory responses occurred despite a catecholamine-induced blood acidosis (a potential ventilatory stimulant). To assess the importance of initial Vw and/or blood respiratory status on catecholamine-mediated hypoventilation, these experiments were repeated under hyperoxic (PwO2 = 640 Torr) hyperoxic hypercapnic (PwO2 = 510 Torr, PwCO2 = 4.8 Torr) or normoxic (PwO2 = 151 Torr) conditions in which Vw was either depressed (3.9-fold during hyperoxia) or unaffected. Intra arterial infusion of catecholamines did not affect Vw under either of these experimental conditions. These results demonstrate that during a respiratory challenge, such as hypoxia or hypercapnia, physiologically relevant levels of circulating catecholamines can depress Vw and therefore do not support a stimulatory role for circulating catecholamines in the control of ventilation in fish. PMID- 1906628 TI - Modulation of equine tracheal smooth muscle contractility by epithelial-derived and cyclooxygenase metabolites. AB - The role of epithelium in the modulation of contractile responses to electrical field stimulation (EFS), acetylcholine (ACh), and KCl were studied in vitro in strips of equine tracheal smooth muscle (TSM). EFS with 0.5 ms pulses of voltage (70 V) resulted in frequency dependent contractions of equine TSM that were sensitive to tetrodotoxin (TTX) and atropine. In TSM without epithelium, preincubation with indomethacin significantly potentiated contractile responses to EFS. The potentiating effect of indomethacin on EFS contractions was abolished by the addition of 3 nM prostaglandin E2 (PGE2). ACh and KCl cumulative concentration-response curves were shifted to the left by removal of epithelium from equine TSM strips with a significant decrease in the 50% effective concentration (EC50) for both ACh and KCl. The mean EC50 (+/- SE) for ACh in TSM without epithelium was 0.51 +/- 0.09 microM vs 4.30 +/- 1.03 microM in TSM with epithelium. Similarly, the mean EC50 (+/- SE) for KCl in TSM without epithelium was 22.20 +/- 2.61 mM vs 32.35 +/- 2.66 mM in TSM with epithelium. The addition of indomethacin (3 microM) had no effect on the ACh concentration-response curves in TSM strips with or without epithelium. Our results suggest that in the equine airway there is (1) an epithelial-derived relaxant factor that modulates tracheal smooth muscle contractility postsynaptically, and (2) a nonepithelial-derived inhibitory factor, possibly PGE2, that modulates ACh release from nerves presynaptically. PMID- 1906630 TI - [Salmonella paratyphi A urinary infection in Schistosoma mansoni bilharziasis]. AB - The authors report a case of urinary tract infection caused by Salmonella paratyphi A in a patient with Schistosoma mansoni bilharziasis and describe the symbiotic relationship between these two micro-organisms. The association was not fortuitous: schistosomes behave as reservoirs of bacteria and can cause bacterial discharges followed by a long carrying period. PMID- 1906631 TI - [Anti-infective prophylactic measures in cesareans]. AB - Septic complications remain important in obstetrical surgery due to the serious threat they pose to life and the sequelae which they may leave. The authors have therefore attempted to identify which of the anti-infectious prophylactic treatments used in cesareans were the most effective. This analysis was based on cases in their unit seen from 1984 to 1988 and on a review of the literature. Of the patients who underwent a cesarean (9.4 percent out of 7,855 deliveries), 2 percent were infected, with and incidence of 0.65 percent serious infections (0.4 percent septicemia). On the basis of the literature, the following risk factors were identified: 1st cesarean, cesarean during labor, rupture of the membranes, surgical problem, anemia, obesity and low socio-economic level. The local fundamental and systemic prophylactic measures taken were special antibiotic prophylaxis in the patients with a risk of infection only. The short protocol, with a single injection of penicillin A or a first generation cephalosporin, after clamping the umbilical was preferable and, according to all the studies, had the advantage of avoiding the selection of resistance. PMID- 1906632 TI - Chronic evolution of acute hepatitis B: the significance of simultaneous infections with hepatitis C and D. Copenhagen Hepatitis Acuta Programme. AB - Seventy-six of 77 consecutive patients with hepatitis B surface antigen (HBsAg) positive acute hepatitis were reevaluated using anti-hepatitis C virus (HCV), anti-hepatitis D virus (HDV), and IgM anti-hepatitis B core (HBc) testing. Anti HCV and/or anti-HDV was found in 32 patients (42%). The presence of these markers was significantly associated with intravenous drug abuse (p less than 10(-6). Sixty-nine patients were IgM anti-HBc-positive, of whom two (3%) (95% confidence limits, 1-12%) became chronic HBsAg carriers with histologically verified chronic liver disease; both were anti-HCV and anti-HDV-negative. Among the remaining 67 IgM anti-HBc-positive patients 8 had HBV and HDV co-infection, 3 had HBV and HCV co-infection, and 1 had HBV, HCV, and HDV co-infection. Twenty-two had evidence of preceding or past HCV infection; two developed chronic active hepatitis in spite of HBsAg clearance. Seven patients with IgM anti-HBc negative. One was a chronic HBsAg carrier with HDV superinfection. One had subclinical acute HBV infection and became a chronic HBsAg carrier. In a further two patients reactivation of replication in a chronic HBV infection could not be disregarded. Three patients could not be classified; all had acute recent onset of symptoms, cleared HBsAg within 6 months, but lacked IgM anti-HBc. It is concluded that HCV and HDV superinfections in HBV carriers mimicking acute HBV infection with chronic evolution are rarely encountered in the present population in spite of high frequency of both HCV and HDV markers. PMID- 1906633 TI - Neisseria meningitidis with reduced sensitivity to penicillin: observations in 10 children. AB - 10/84 strains (11.9%) of Neisseria meningitidis isolated from blood and/or cerebrospinal fluid in children 1986-1987 had reduced sensitivity to benzylpenicillin (MICs 0.1-0.4 mg/l). Group C meningococci predominated among these strains. The clinical course was satisfactory in all cases regardless of the antibiotic treatment used, although the time to abatement of fever was prolonged compared to that of children infected with susceptible strains. PMID- 1906634 TI - Effect of lactic acid producing bacteria on the human intestinal microflora during ampicillin treatment. AB - 20 healthy volunteers participated in a double blind study concerning the effect of lactic acid producing bacteria on the intestinal microflora during ampicillin treatment. 10 volunteers received 500 mg ampicillin tablets t.i.d. together with capsules containing lactic acid producing bacteria (Lactobacillus acidophilus and Bifidobacterium bifidum) for 7 days, and the other 10 volunteers were given 500 mg ampicillin tablets together with placebo capsules t.i.d. for 7 days. Both groups of volunteers continued the intake of the capsules t.i.d. for another 14 days after the ampicillin administration had been completed. The number of enterococci, streptococci and corynebacteria decreased during ampicillin administration but returned to normal levels after 14 days. Yeasts increased during the antibiotic treatment but returned to the same levels as before treatment within 14 days. Escherichia coli strains were suppressed in most volunteers during ampicillin administration. The numbers of anaerobic gram positive cocci and rods decreased in most subjects during ampicillin treatment but were normalized within 2 weeks. Bacteroides strains were recovered in higher numbers in the lactic acid producing bacteria group compared to the placebo group. The volunteers receiving lactic acid producing bacteria were recolonized slightly faster than those having placebo. There were adverse effects observed in 3 subjects receiving ampicillin plus placebo. In the lactic acid producing bacteria group, one subject had diarrhoea on day 3 to on day 3 to day 7. PMID- 1906635 TI - Reflections on funding the National Health Service: from illusion to reality? AB - Opinions differ about how best we organise our services to promote and preserve it, meet their costs and apportion them between the individual and the state. The well-being of the NHS is imperilled and its development is impeded by underfunding, a state of affairs likely to persist as long as it depends exclusively on Exchequer monies. To break the impasse the public should reconsider its attitude to the imposition of health charges, the marketing of health services, and coll raboration between the NHS, public bodies and private groups. The able-bodied might well, within their means, bear some of the costs of the services they use. The NHS would profit from a rapprochement with private medicine. A more prompt and positive response by the NHS to clinical and social challenges might be facilitated if its ties to government were loosened and it was overseen by an independent agency. Free health is a Utopian ideal. In the real world the best we are likely to achieve is an up-to-date health service which gives a fair deal to patients, who are its raison d'etre, and to those who provide the money to pay for it; it should syncretise the art and science of medicine. PMID- 1906636 TI - Pseudogout associated with the use of cyclical etidronate therapy. AB - Recently the use of etidronate in a cyclical fashion has been shown to be of value in the treatment of osteoporosis. Like all bisphosphonates etidronate is structurally similar to pyrophosphate, further it is also known to interfere with phosphate handling by the kidney resulting in elevated plasma phosphate levels. This report describes the case of a patient with established osteoporosis who developed pseudogout associated with cyclical etidronate use. The possible mechanism responsible for this is discussed. PMID- 1906637 TI - Regulatory role of parasites: impact on host population shifts with resource availability. AB - Effects of infections by the ciliate Lambornella clarki on larval populations of its mosquito host Aedes sierrensis were examined in laboratory and field studies. When host populations developed with sufficient food, mortality from parasites was additive and reduced the number of emerging mosquitoes. For food-limited populations, mortality was compensatory or depensatory; emerging adults were as or more abundant with higher average fitness than those from uninfected control populations. When nutrients were scarce, parasitic infections relaxed larval competition and increased per capita food by reducing host abundance. Food limitation altered larval feeding behavior, reducing horizontal transmission and subsequent mortality from parasitism. PMID- 1906638 TI - [New galenic presentations]. PMID- 1906639 TI - [Prevalence and features of pre-B-cell acute lymphoblastic leukemia in Mexico: description of 9 patients]. AB - A group of 9 patients with pre-B cell acute lymphoblastic leukaemia (pre-B ALL) was identified prospectively within 209 patients with ALL. This variant of leukaemia was defined by the presence of heavy mu-chains in the cytoplasm of the malignant cells, and no surface immunoglobulins. Four patients displayed the CD10 (CALLA) antigen, in addition to cytoplasmic mu chains. A G-0 acute leukaemia (no blast cells in S-phase) was identified in two cases. Response to treatment of the patients was poor: Only four achieved complete remission; median survival was 24 weeks and the 40-week disease free survival was 20%. These figures are significantly worse than those obtained in patients with early-pre-B (CD10+) ALL. We conclude that the prevalence of pre-B ALL is low in our experience (4.6% of all patients with ALL) and that a poor outcome of treatment was related to it. PMID- 1906640 TI - Acquired auto-anti D in a patient with myelodysplastic syndrome. AB - Modification of blood group in the course of malignant haemopathy in an aged patients is described. To our knowledge, this is the first published case describing the appearance of autoantibody due to anti-D in a patient with Rh typing DCcee who has myelodysplastic syndrome in transition to acute leukaemia. We present a patient who developed acquired autoantibody to Rh locus as co phenomenon of myelodysplastic syndrome in transition to acute leukaemia. PMID- 1906641 TI - [Determination of t-PA and PAI-1: recommendations for the collection of samples]. PMID- 1906642 TI - Half-life of single-chain urokinase-type plasminogen activator (scu-PA) and two chain urokinase-type plasminogen activator (tcu-PA) in patients with acute myocardial infarction. AB - The pharmacokinetics of urokinase (two-chain urokinase-type plasminogen activator, tcu-PA) and single-chain urokinase-type plasminogen activator (scu-PA) were studied in 20 patients with acute myocardial infarction (AMI). Ten consecutive patients received 2.5 million units tcu-PA by bolus injection within 5 min during the first 6 h after AMI (group I). Ten further consecutive patients received 250,000 U tcu-PA within 5 min, followed by 4.5 million U scu-PA by intravenous infusion over 40 min (group II). An enzyme immunoassay was developed for urokinase antigen determinations, and a fibrin plate assay for determinations of fibrinolytic activity was applied. Using a 3-compartment model, in group I 98% of urokinase antigen were cleared with a half-life of 60.8 min. After scu-PA, urokinase antigen was cleared with half-lives (area under the curve in parentheses) of 6.9 min (74.8%), 26.5 min (23.6%), and 329.7 min (2.2%). The half disappearance times of fibrinolytic activity were 18 and 8 min in group I and II, respectively. A more pronounced decrease of plasminogen was observed after tcu PA. PMID- 1906643 TI - Modulation of cytoskeletal organization and cytosolic granule distribution by verapamil in amphibian urinary epithelia. AB - The present study examines the role of calcium in modulating epithelial cytomorphology by using verapamil, a calcium antagonist, and considering its effects on cytosolic granule distribution and exocytosis in toad urinary bladder. The effect of verapamil on the detection and distribution of microfilaments in toad urinary bladder using immunogold labeling techniques in toad urinary bladder epithelial cells was also examined. Verapamil, which inhibits antidiuretic hormone (ADH)-mediated water flow, increased the number, size and distribution of dense calcium-containing secretory granules in bladder epithelial cells. This calcium antagonist prevented granule exocytosis, such that, six-times the number of granules were present in verapamil-treated tissues. The normal cytomorphological changes that accompany the actions of ADH were attenuated by verapamil, including ADH-induction of microvilli. ADH increased the number of actin microfilaments as determined using protein A-gold by immunolabeling, whereas, verapamil treatment was unremarkable as compared to control. The results suggest that calcium may play a prominent role in mediating granule exocytosis and membrane fusion events that normally accompany hormone action. PMID- 1906644 TI - The role of chronic acanthosis and subacute inflammation in tumor promotion in CD 1 mice by petroleum middle distillates. AB - An initiation-promotion bioassay using CD-1 mice was conducted to examine the role of chronic acanthosis and inflammation in tumor promotion by petroleum middle distillates (MD). Test groups were initiated with 7,12 dimethylbenz[a]anthracene (DMBA). Promotion with MD consisted of twice weekly treatments for 25 weeks with either 25 or 50 microliters, 50 microliters + daily treatment with 15 micrograms dexamethasone, 50 microliters + postapplication washings, or 100 microliters. Three mice from each group were euthanized at 21 day intervals (24 total per group). The skin from interim euthanized mice was examined histopathologically for tumors, acanthosis, and subacute inflammation. Tumor incidence at study termination was as follows: 25 microliters (45%), 50 microliters (43%), 50 microliters + dexamethasone (0%), 50 microliters + washing (70%), and 100 microliters (81%). A correlation of greater than 0.93 was observed at all intervals between tumor incidence and cumulative group mean degrees of acanthosis in interim euthanized mice. The correlation between subacute inflammation at early through midstudy interval weeks and tumor incidence at study termination was poor. These results support the hypothesis that induction of a lasting, albeit mild, hyperplasia is an essential, but not sufficient requirement for tumor promotion. Furthermore, subacute inflammation does not appear to be a significant factor in tumor promotion by petroleum MD. PMID- 1906645 TI - Direct and microsomal activated aflatoxin B1 exposure and its effects on turkey peritoneal macrophage functions in vitro. AB - Sephadex-elicited turkey peritoneal exudate cells were used to establish adherent macrophage monolayers on glass coverslips in order to determine the effects of aflatoxin B1 (AFB1) on macrophages. Adherent macrophage monolayers were exposed to increasing doses of AFB1 (5, 10, 20, and 40 micrograms), either directly, or to 0.01, 0.1, 0.5, 1, and 5 micrograms of AFB1 in the presence of a chicken microsomal mixed function oxidase system (MFO). Cultures were incubated with the appropriate treatments for 1 hr, then washed and allowed to recover in fresh growth medium for 2 hr. Direct exposure of macrophages to AFB1 had no detrimental effect on macrophage adherence, percentage damaged, percentage phagocytic, and the number of antibody-coated or uncoated sheep red blood cells internalized per phagocytic macrophage when compared with the sham or solvent treated cultures. However, the addition of MFOs to the cultures treated with much lower doses of AFB1 resulted in significantly higher morphological alterations along with a reduction in cell adherence and phagocytic potential. Addition of piperonyl butoxide (a P450 inhibitor) abrogated AFB1-MFO induced alterations. Data collected in this study suggest that turkey macrophages are resistant to the direct exposure of AFB1 and that AFB1 induced alterations in macrophage effector functions are due to metabolic activation of AFB1 by MFOs. PMID- 1906646 TI - Cerebral hemorrhagic risk of aspirin or heparin therapy with thrombolytic treatment in rabbits. AB - We studied the incidence of cerebral hemorrhage in an animal model of embolic stroke to determine the safety of aspirin, heparin, and tissue plasminogen activator therapies. We occluded the middle cerebral arteries of rabbits with labeled blood clots and administered either tissue plasminogen activator, heparin, aspirin, tissue plasminogen activator plus aspirin, tissue plasminogen activator plus heparin, or saline at various times after stroke. Compared to saline controls, both the aspirin-only and the tissue plasminogen activator-plus aspirin groups had a significantly higher incidence of cerebral hemorrhage, whereas the heparin and tissue plasminogen activator combination groups did not. We conclude that aspirin antiplatelet therapy alone may increase the risk of hemorrhagic infarction, whereas heparin or tissue plasminogen activator therapy appears to be relatively safe. PMID- 1906647 TI - Interaction between free radicals and excitatory amino acids in the formation of ischemic brain edema in rats. AB - Both oxygen free radicals and excitatory amino acids have been implicated as important cellular toxins in ischemic brain. Recent in vitro studies suggest that there may be a mutual interaction between these two mediators. We explored the relation between oxygen free radicals and excitatory amino acids in the development of ischemic brain edema in vivo. Male Sprague-Dawley rats were treated with the free radical scavenger dimethylthiourea 1 hour before ischemia or with the excitotoxin antagonist MK-801 30 minutes before ischemia produced by occlusion of the middle cerebral artery. Groups of seven or eight animals were treated with vehicle, low-dose (375 mg/kg) dimethylthiourea, high-dose (750 mg/kg) dimethylthiourea, low-dose (0.5 mg/kg) MK-801, high-dose (2.0 mg/kg) MK 801, or both high-dose dimethylthiourea and low-dose MK-801. After 4 hours of ischemia, brain water content was determined. In eight vehicle-treated controls, mean +/- SEM water content of tissue in the center of the ischemic zone was 83.29 +/- 0.18%. A significant reduction of brain edema was observed in all drug treated groups: for example, 50.2% (p less than 0.001) in the high-dose dimethylthiourea group, 53.7% (p less than 0.001) in the low-dose MK-801 group, and 66.4% (p less than 0.001) in the combined dimethylthiourea and MK-801 group. Combined treatment with dimethylthiourea and MK-801 provided no significant additive effect over that resulting from treatment with MK-801 alone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1906648 TI - Parasitic infections, an uncommon risk of blood transfusion in the United States. PMID- 1906649 TI - Red cell transfusions in total knee and total hip replacement surgery. AB - To explore how red cell transfusions were used to support patients who underwent primary and revision hip and knee replacements classified within diagnosis related group (DRG) 209 (major joint and limb reattachment procedures), we studied abstracted patient discharge records from 151 United States hospitals in 1986. A total of 9684 units of whole blood and/or separated red cells was used to support 6472 patients. The transfusion use varied by surgical procedure, with patient gender as an influencing factor. Large proportions of patients underwent surgery without requiring transfusion. Among transfused patients, the majority received 1 to 3 units of red cells; however, a minority of patients required multiple transfusions, thereby utilizing a disproportionate share of the blood resource. Comparison of transfusion practice within the seven most active hospitals revealed significant differences (p less than or equal to 0.01) in the percentage of patients actually transfused, but not in the mean number of units of red cell components transfused per transfused patient. Similar findings emerged from comparison of transfusion practice when all hospitals were segregated into five hospital classes on the basis of orthopedic surgical service activity. These effects were seen for both total knee and total hip replacement procedures. It can be concluded that the lack of clearly defined criteria for transfusion contributed to the variations observed. PMID- 1906650 TI - Trypanosoma cruzi, the etiologic agent of Chagas' disease: status in the blood supply in endemic and nonendemic countries. PMID- 1906651 TI - The manufacture of factor VIII concentrates. PMID- 1906652 TI - [Ignition of the endotracheal tube during CO2 laser therapy of upper airway disorders]. AB - The patient had papillomas in larynx, trachea and the main bronchi and was treated with CO2-laser evaporation under general anaesthesia. He was intubated with a red rubber tube wrapped with aluminum tape and outermost with muslin strips. The muslin was soaked in water before intubation. After using the CO2 laser with 15W for 3-5 s a continuous smoke generation was seen. The muslin strips had glowed away. The fire was immediately extinguished with water and no damage to the airway had occurred. PMID- 1906653 TI - Safe and cost-effective methods of diving in contaminated water in the Midwest. PMID- 1906654 TI - Care of the elderly in north and west Belfast. AB - A survey of all elderly people aged 65 years and over from North and West Belfast receiving long-term care in residential and nursing homes, and in psycho geriatric and geriatric care was undertaken. A total of 967 subjects was studied and physical dependency and mental impairment documented. The high dependency of residents in geriatric and psycho-geriatric care was highlighted, with greater levels of dependency than among those receiving nursing home care. Professional assessment prior to admission should be common to all long-term care facilities and is essential if services for the projected demographic increase in numbers of very elderly people are to be provided, and inappropriate admission and expenditure avoided. PMID- 1906656 TI - Experimental bacterial prostatitis in rats. AB - Experimental acute bacterial prostatitis in rats was induced by four different routes of bacterial inoculation. The most simple and reproducible method of producing bacterial prostatitis was to instil the bacterial suspension into the prostatic urethra after the administration of an appropriate antibiotic to prevent associated pyelonephritis. PMID- 1906655 TI - Does a gonadotropin-releasing hormone analogue prevent cisplatin-induced spermatogenic impairment? An experimental study in the mouse. AB - The cytotoxic effect of cis-diamminedichloroplatinum II (cisplatin, CDDP) on spermatogenesis in BALB/C mice, and possible protection of the testes by leuprolide acetate (D-Leu-6 LHRH(1-9)-ethylamide, TAP-144, leuprolide), a synthetic gonadotropin-releasing hormone analogue, were examined. Temporary interruption of the pituitary-gonadal axis by the analogue and amelioration of the gonadal toxicity of cisplatin by reducing the cell division rate in spermatogenesis were expected. The results showed cisplatin to have a cytotoxic effect on spermatogenic cells in BALB/C mice. The administration of leuprolide had no effect on testicular weight or histological findings in the mouse testes. Pretreatment and simultaneous administration of leuprolide did not reduce the damaging effect of cisplatin on the testes in mice. This is at variance with a previously published report. PMID- 1906657 TI - High osmolality-low pH flush solutions improve renal transplant function in rats. AB - Although transplanting rat kidneys is an established microsurgical technique, inulin clearance is abnormally low, due to rejection and/or warm ischemia-induced damage. In the present studies, rejection was avoided by using inbred Brown Norway rats as donors and recipients. Donor kidneys were flushed with ice-cold solutions of various composition (saline, saline + 200 or 400 mM mannitol) and pHs (5.7, 6.4, and 7.4), and the kidneys were kept cold during transplantation into unilaterally nephrectomized recipients. Renal function was assessed by clearance techniques 1 week later. In control rats, with both native kidneys intact, the ratio of inulin clearance, left kidney to right kidney, was 0.99 +/- 0.02. In rats with a native right kidney and a transplanted left kidney that had been flushed with saline, the ratio was considerably lower (0.46 +/- 0.09). Adding 200 mM mannitol to the saline flush solution increased the ratio (0.89 +/- 0.09). In comparison, adding 200 mM mannitol and 5 mM phosphate buffer at pH 7.4 resulted in a somewhat lower ratio (0.80 +/- 0.09), whereas adding 200 mM mannitol and 5 mM phosphate buffer at pH 5.7 resulted in a higher ratio, one that was indistinguishable from control (0.97 +/- 0.09). Thus, in this latter group, the inulin clearances of the transplanted kidneys were identical to those of the contralateral native kidneys. PMID- 1906658 TI - In vitro sensitivity testing of human renal cell carcinoma with cytostatic agents and interferon alpha-2a. AB - Samples of 38 human renal cell carcinomas (RCC) were subjected to routine histopathological examination but also to in vitro sensitivity testing with mitomycin C, vinblastine and interferon Alpha-2a at various concentrations corresponding to serum titers recommended to be effective in vivo, employing a monolayer assay. Extending earlier in vitro studies, both tumor cell kill rates (TCKR) and proliferation rates (PR) were assessed. Following in vitro preparation the tumor cell cultures were simultaneously exposed to the anticancer drugs listed above. The proliferation rates were determined immunocytochemically using the monoclonal antibody Ki-67. Nine (23.7%) of the tumors investigated revealed temporary and limited response with respect to either TCKR or PR. Improvement of this percentage could only be obtained by increasing drug concentration to titers with toxicity intolerable for in vivo administration. The in vivo data presented correspond to clinical temporary and limited remissions in patients with metastatic RCC ranging up to 25%. PMID- 1906659 TI - Differential sensitivity of renal cell carcinoma xenografts towards therapy with interferon-alpha, interferon-gamma, tumor necrosis factor and their combinations. AB - Whereas cytokine therapy has proven efficacy in the treatment of metastatic renal cell carcinoma (RCC), many questions regarding the use of these drugs remain unanswered. In the present study we evaluated the antiproliferative effects of human recombinant alpha-interferon (IFN), gamma-interferon and tumor necrosis factor-alpha (TNF) on eight human RCC xenografts. In particular, the importance of the administration route, dosage and tumor load was investigated. Response to the cytokines differed widely amongst the different tumors. Of three tested routes of administration (i.v., i.p. and s.c. peritumoral), only the s.c. peritumoral route was effective against tumor growth. After 6 weeks of therapy consisting of 150 or 1,500 units IFN/g given s.c. peritumorally three times a week or 30,000 units TNF/g given five times a week, alpha-IFN treatment resulted in 2%-100% growth inhibition; gamma-IFN, in 7%-80%; and TNF, in 35%-75% as compared with the untreated control. Growth of five of eight tumor lines could be inhibited completely by combinations of IFN and TNF, whereby the tumor dimensions at the beginning of therapy were decisive for the results. In some cases IFNs had optimal doses; however, the antitumor effects of TNF were always dose-dependent. Our studies indicate that the doses at which the optimal direct effects of cytokines are measured are critically dependent on the tumor treated. Although direct effects are only one part of the mode of action of cytokines, our results indicate that dosage of cytokines may need individualisation. PMID- 1906660 TI - HIV-specific humoral and cellular immunity in rabbits vaccinated with recombinant human immunodeficiency virus-like gag-env particles. AB - Recombinant human immunodeficiency virus type-1 (HIV-1)-like gag-env particles produced in mammalian cells were inoculated into two New Zealand white rabbits. In parallel, two control rabbits were inoculated with the homologous HIV-1 virions inactivated by ultra violet light (uv) and psoralen treatments. The humoral and cellular immune responses to HIV-1 were evaluated for both groups of animals. Recombinant particles elicited humoral immunity that was specific for all the viral structural proteins. The antibodies recognized both denatured and nondenatured proteins. Moreover, the sera neutralized the in vitro infectivity of the homologous virus in CEM cells. Importantly, the recombinant particles also generated a T helper response by priming with the HIV proteins. Similar results were observed with inactivated virus immunization. Therefore, our results suggest that the recombinant HIV-like particles elicit functional humoral immunity as well as cellular immunity and represent a novel vaccine candidate for AIDS. PMID- 1906661 TI - [Endodontics in primary dentition]. PMID- 1906662 TI - A technique for the collection of reticular effluent of sheep. AB - Two sheep were equipped with rumen and omasal fistulae. A teflon tube with 1 mm outer diameter (OD) was permanently fixed between the abomasal fistula and the reticulo-omasal orifice. The effluent sampling tube was introduced through the abomasal cannula, through the omasal canal into the reticulo-omasal orifice by aid of the teflon tube. The technique allowed direct collection of reticular effluent from sheep. Intermittent flow of reticular effluent was observed. The moments of flow coincided with the end of the second phase of reticular contractions. From the flow pattern it was concluded that the motility of the reticulo-omasal orifice was not affected by the sampling procedure. From the similarities in the pH values, DM contents, and total protozoal counts in the effluent and in the reticular samples, it was concluded that representative samples of effluent could be obtained by the method. One animal was used for sampling for a period of eight months and then again 2 1/2 years later. A fraction of 97 to 98% of the DM present in the reticular effluent and in the reticular samples passed a sieve with 1 mm pore size. From the analyses of reticular content and reticular effluent it was concluded that the reticulo omasal orifice does not have a significant discriminating function for the selective passage of particles and protozoa into the omasum. PMID- 1906663 TI - Modification of the cutting thread technique for intestinal anastomoses using diathermy. AB - The author has modified a surgical technique, which was originally developed at the turn of the century, for the aseptic establishment of an intestinal anastomosis. The principle of this technique, known as the "cutting thread" principle, was that a loop of thread was introduced into the lumen of each of two approximated loops of intestine. After suturing the two loops of intestine together around the intraluminal parts of the thread, the latter was used as a "wire-saw" to create a stoma between the two intestinal loops. The author modified the method in such a way that the cutting could be performed with diathermy, thus avoiding the risk of uncontrollable traumatization which was inherent in the original technique. The author also used "steering" sutures which encircled the diathermy wire, preventing the wire from running "off the line". The cutting thread of the original method was replaced by a silver-plated copper wire, insulated with teflon except for a few mm in the middle and a few cm at each end. The stoma was cut with diathermy, using the uninsulated middle of the wire as an electrode. After testing in experimental animals, this technique appears to be of value in certain clinical operations, e.g. implantation of the small intestine into the caecum or colon following an ileal respective caecal resection in the horse. PMID- 1906664 TI - Effect of energy/protein ratio on productive performance and carcass composition of male broilers. AB - To minimize excessive carcass fatness of broiler chicken, a diet with a low energy/protein ratio (EPR 117 resulting from 2800 Kcal ME/kg and 24% crude protein) was fed between days 7-14 (E1), 7-21 (E2) or 21-35 (E3); the rest of the time, up to 49 days of age, the chicks were fed as the control group, with EPR's of 138, 162 and 181 according to age. The results indicate that the feeding of a ration with a low EPR at different ages did not importantly impair productive performance although treatments E2 and E3 produced lower live weights and a decreased feed conversion (P less than or equal to 0.03). Concerning carcass characteristics, there was a trend to lower abdominal fat content in all experimental groups as compared to the control group and a lower ether extract content in the edible part of broilers from treatments E2 and E3 (P less than or equal to 0.06). More research is needed to find a metabolic explanation for these feeding effects. PMID- 1906665 TI - An automated method for determination of total bile acid concentration in canine serum. AB - The purpose of the study was to evaluate an automated modification of the enzymatic method, Enzabile (Nycomed) for the determination of total bile acid concentration in canine serum. Evaluation of the automated method was accomplished by measuring the within-run and between-day variation, by assessment of accuracy, and by assessment of detectability of the method. The automated method was found to correlate well with the original Enzabile (Nycomed) method. The resulting regression equation was found to be: y = 5.81 + 1.09 x, r = 0.99. Also, the variations and the detection limit of the automated method were smaller, respectively lower, compared to the reference method. PMID- 1906666 TI - Cytogenetic characterization of mammary tumors in two domestic dogs. AB - Tumor cells of two cases of mammary neoplasms in dog were investigated cytogenetically. An 11-year-old cocker spaniel showed a marked X-chromosome in most metaphases (80%). In a 12-year-old poodle, tumor cells with the following abnormalities were found: trisomy 1, monosomy X and two marker chromosomes. PMID- 1906667 TI - Lobeline-induced hyperpnea in equids. Comparison with rebreathing bag and exercise. AB - In order to facilitate lung auscultation, a transitory hyperpnea may be obtained by lobeline administration, use of a rebreathing bag or exercise. The effect of these three methods on the pulmonary function were studied and compared in 5 healthy ponies. Respiratory airflow and tidal volume were measured with a pneumotachograph Nr. 5 and pleural pressure with the esophageal balloon catheter technique. Pulmonary function values were measured before, during and after the hyperpnea induced by (i) lobeline, (ii) rebreathing and (iii) exercise. Lobeline administration induced an hyperpnea due to both an increase in tidal volume and respiratory rate; this increase in ventilation lasted for about 90 s and was accompanied by a sharp rise in the respiratory peak airflows, especially the expiratory ones. The rebreathing method induced a less hyperpnea which lasted only 30 s. Lastly the hyperpnea after a light treadmill exercise was the longer in duration and intermediate between the preceding methods in intensity. PMID- 1906668 TI - Distribution of immunoglobulins during embryogenesis in the chicken. AB - Whereas the yolk of freshly-laid eggs contains only IgG, apart from traces of IgA, we were able to measure, on average, 0.145 mg/ml IgM and 0.207 mg/ml IgA in the yolk sac contents of 21-day-old chicken embryos. Up to the 14th embryonic day, IgG is exclusively contained in the yolk sac contents. It was not possible to demonstrate an increase in the amount of immunoglobulins present by comparing the amounts of IgM and IgA in freshly-laid eggs and in the yolk sac contents of 21-day-old embryos. The offspring of hens with experimentally-induced agammaglobulinemia did not begin with the production of the immunoglobulin isotypes IgG, IgM and IgA until after hatching. From these results the conclusion can be drawn that the immunoglobulins IgM and IgA are transferred from the egg white to the yolk sac contents during the last third of embryonic development. Embryonic synthesis of these immunoglobulins can be discounted as a result of this study. Synthesis was found to be initiated between the 2nd and 7th day of life for IgG, between the 2nd and 4th day of life for IgM and between the 6th and 13th day of life for IgA. PMID- 1906669 TI - Marrow storage techniques: a clinical comparison of refrigeration versus cryopreservation. AB - Fifty-three patients were evaluated for a comparison of the efficacy, safety, and cost efficiency of bone marrow (BM) transplanted after either refrigeration or cryopreservation. Thirty-eight patients had BM stored at 4 degrees C for an average of 3 days and 15 patients had cryopreserved BM stored for an average of 56 days. The average number of cells harvested was 3.8 x 10(8)/kg. The time to WBC recovery greater than 1 x 10(9)/l was 17 days refrigerated and 23 days for cryopreserved BM. The time to platelet recovery greater than 20 x 10(9)/l was 24 days for refrigeration storage and 51 days for cryopreserved BM. Four of 38 patients with refrigerated vs. 4/15 patients with cryopreserved BM experienced delayed engraftment (p less than 0.05). Refrigeration storage requires no special equipment, is cheaper than and presents a safe and viable alternative to cryopreserved BM in reconstituting hemopoiesis following high-dose chemo radiotherapy. PMID- 1906671 TI - Rebreathing during oxygen treatment with face mask. The effect of oxygen flow rates on ventilation. AB - The influence of different oxygen flow rates on ventilation and arterial blood gases was investigated in ten healthy volunteers during oxygen treatment with the Hudson mask. Respiratory parameters were calculated using inductive plethysmography calibrated against pneumotachography. The minute ventilation was greater when using the mask with oxygen flow rates less than 5 l/min compared to when no mask was used. With an oxygen flow rate of 3 l/min, minute ventilation was about 140% of minute ventilation without face mask. With 0 l/min, minute ventilation increased to about 160%. The increase in minute ventilation was mainly due to an increase in tidal volume. No change was seen, however, in PaCO2 with different oxygen flow rates. Secondary objective signs following an increase in respiratory work (changes in heart rate, systolic blood pressure and oxygen saturation) were not seen. We recommend 5 l/min as the lowest oxygen flow rate to be used during oxygen therapy with the Hudson mask, in order to avoid rebreathing and excessive respiratory work. PMID- 1906672 TI - The independent metabolic effects of enflurane anaesthesia and surgery. AB - The metabolic effects of enflurane anaesthesia (1MAC) in air/oxygen were investigated in six healthy unpremedicated women scheduled for total abdominal hysterectomy (TAH). The changes in acid-base status, CO2 production, and circulating concentration of total protein, albumin and a variety of metabolites (glucose, lactate, glycerol and alanine) were measured before and during a 2-h period of anaesthesia alone, during 1 h of anaesthesia plus surgery, and in the recovery period. The subjects were maintained normothermic (36.5 +/- 0.3 degrees C), and with an arterial SaO2 above 95% throughout the period of study. The circulating concentration of all metabolites changed little as a result of anaesthesia alone, but the glucose and lactate levels rose rapidly after the onset of surgery (P less than 0.05). Plasma albumin and total protein concentration decreased during the study, reaching values that were significantly lower than the pre-anaesthetic values (P less than 0.05). CO2 production decreased by 9% during anaesthesia and surgery, but returned towards preoperative values during recovery. This study provides no evidence of any significant effect of enflurane anaesthesia alone on human intermediary metabolism. Most of the changes in circulating metabolite concentrations observed during and after anaesthesia and surgery are likely to be due to the surgical stress. PMID- 1906670 TI - Myelodysplastic syndrome and acquired factor VIII inhibitor with severe subcutaneous haemorrhage. AB - A case of acquired haemophilia A presenting with extensive spontaneous bruising and anaemia is reported. The anaemia was due to myelodysplastic syndrome (FAB: refractory anaemia with ringed sideroblasts). A factor-VII:C-specific inhibitor was also found. Prednisone and pyridoxine were given, and the inhibitor became undetectable after 4 weeks of therapy, but the abnormal ringed sideroblasts still persisted on repeated bone marrow biopsy. PMID- 1906673 TI - Prolactin responses to thyrotropin-releasing hormone in multi-infarct dementia and senile dementia of the Alzheimer type. AB - The serum prolactin (PRL) responses to stimulation with thyrotropin-releasing hormone (TRH) (500 micrograms Protirelin) were compared in 14 patients with multi infarct dementia (MID) and 10 patients with senile dementia of the Alzheimer type (SDAT). Between the MID and the SDAT patients, there were no statistically significant differences in the median serum PRL concentrations, median changes in serum PRL concentrations or median proportional changes in serum PRL concentrations. Further, the serum PRL responses did not correlate with the GBS scale scores (degrees of dementia) or the GBS subscale scores (clinical profiles, including motor functioning, emotional functioning and intellectual functioning). In conclusion, the study does not support the hypothesis that serum PRL responses to TRH stimulation are of diagnostic value in differentiating between MID and SDAT. PMID- 1906674 TI - Lathyrism and western Pacific amyotrophic lateral sclerosis: etiology of short and long latency motor system disorders. PMID- 1906675 TI - Human immunoglobulin heavy-chain variable region genes: organization, polymorphism, and expression. PMID- 1906676 TI - Does age influence the bioactivity of follicle-stimulating hormone in men? AB - We measured follicle-stimulating hormone (FSH) by both standard radio-immunoassay (RIA) and bioassay (Bio) methods in 56 men, using a modification of a previously described in vitro granulosa cell bioassay for the determination of the bioactivity of FSH. Thirty-four were young (mean age 25 years), and 22 elderly (mean age 72). No interfering factors such as disease or alcoholism could be identified. The elderly men had higher RIA-FSH levels compared with the younger ones. Bio-FSH demonstrated a similar trend and therefore the Bio/Immuno ratio was practically constant (3.3 +/- 0.6 vs. 2.7 +/- 0.4). We conclude that the age associated decline in testicular function seen in normal ageing cannot be attributed to a chronic change in FSH activity. Not only is the RIA-FSH elevated among the elderly, it is of the same biological quality as in the younger men. The underlying cause for the testicular function decline is probably at the level of the testis itself. PMID- 1906677 TI - The association of age with dosage requirement for warfarin. AB - Two groups of patients have been studied in order to investigate the relationship between age and the effect of oral anticoagulant therapy. The first group comprised 364 patients aged 23-89 years who showed a stable anticoagulant effect on medium- or long-term warfarin therapy; in this group the elderly subjects were found to require, on average, a lower drug dose to maintain the same degree of anticoagulation. The second group comprised 130 patients aged 15-83 years who had received an initial standard oral dose of 10 mg of warfarin. No significant difference was found in the degree of anticoagulation achieved by 16 hours. Although the maintenance dose in elderly patients is somewhat lower than in younger, the same protocols can be used for the introduction of therapy. PMID- 1906678 TI - Bile duct diverticula and webs: nonspecific cholangiographic features of primary sclerosing cholangitis. AB - Biliary tree diverticula and webs are considered by several authors to be specific cholangiographic features of primary sclerosing cholangitis (PSC). Our experience suggested that these findings can be seen in patients without PSC. The purpose of this study was twofold: to establish whether diverticula and webs are indeed specific for PSC and to assess whether PSC can be accurately diagnosed without reference to diverticula or webs. We retrospectively reviewed 861 consecutive ERCP studies and found 32 cases of webs and/or diverticula. Using accepted cholangiographic, clinical, and histologic criteria, we diagnosed PSC in nine patients and excluded it in 21, with two instances of uncertain diagnoses. Webs and diverticula seen in PSC were cholangiographically indistinguishable from those in the group without PSC. All 21 patients without PSC had other biliary abnormalities, and were grouped by the predominant abnormality or finding believed to be associated with diverticulum or web formation: common duct stones or cholangitis (n = 11 patients), postoperative stricture (n = 4), bile duct stent and balloon dilatation (n = 3), malignant stricture (n = 2), and choledochoduodenostomy (n = 1). To assess cholangiographic diagnosis of PSC in these patients, a blinded reviewer studied the radiographs of the 30 patients with diverticula and/or webs who had confirmed diagnoses. By using established radiologic criteria alone (ignoring diverticula and webs), the correct diagnosis was made in 27, yielding a sensitivity of 89% and specificity of 91%. We conclude that the presence of diverticula and/or webs on a cholangiogram is a nonspecific finding and may be due to inflammation or trauma to the bile duct wall. Further, PSC can be distinguished from other abnormalities on the basis of findings other than diverticula and webs. PMID- 1906679 TI - Program for training staff pharmacists in total parenteral nutrition. AB - A staff development program in total parenteral nutrition (TPN) is described. A 12-week education and training program was developed at a community hospital to enable staff pharmacists (those with B.S. degrees) to become involved in the pharmacy-based TPN service that has been in effect at the institution since 1978. Before 1987, the TPN pharmacist had always held a Pharm.D. degree. In the first four weeks of the program the trainee is allotted two hours per day for required reading. During the final eight weeks, the trainee accompanies a TPN pharmacist on daily rounds. A proficiency examination is given after week 10. Upon successful completion of the program, the pharmacist serves as a nutritional support therapy consultant to physicians who wish to have their patients evaluated, treated, and monitored by the TPN service. A quality assurance program was developed to enable the clinical coordinator in charge of the service to identify areas where further inservice education might be indicated and to satisfy requirements of the Joint Commission. Six staff pharmacists have completed the training program and are allowed to write TPN orders and conduct TPN rounds. The program has expanded the clinical roles of the staff pharmacists and has been well received by the medical staff. The quality assurance monitoring indicates that the service is excellent. A staff development program was successful in training staff pharmacists to participate in TPN therapy. PMID- 1906680 TI - Fibrinolytic parameters in normotensive pregnancy with intrauterine fetal growth retardation and in severe preeclampsia. AB - In pregnancy a decrease in fibrinolytic activity, which is due to an increase in plasminogen activator inhibitor activity and plasminogen activator inhibitor type 1 and type 2, has been described. Because the placenta is a source of both type 1 and type 2 plasminogen activator inhibitor, we have studied them and other fibrinolytic parameters in a group of normotensive pregnant women with intrauterine fetal growth retardation and in two groups of women with preeclampsia, with or without intrauterine growth retardation. A significant increase in plasminogen activator inhibitor type 1 antigen and plasminogen activator inhibitor activity was observed in preeclampsia, with or without intrauterine growth retardation, but not in normotensive pregnancy with intrauterine growth retardation, when compared with normal pregnancy. Plasminogen activator inhibitor type 2 antigen levels showed a significant decrease in both groups of pregnant women (normotensive or preeclamptic) with intrauterine growth retardation when compared with pregnancies without intrauterine growth retardation. A significant correlation between plasminogen activator inhibitor type 2 levels and fetal weight has been observed in the clinical groups. PMID- 1906681 TI - Effects of maternally administered epidermal growth factor on placental permeability. AB - Epidermal growth factor is a well-studied modulator of epithelial membrane structure and function. Mammalian placentas are a rich source of epidermal growth factor receptors, but the role of epidermal growth factor in placental pathophysiologic conditions is unclear. To determine whether epidermal growth factor could affect mechanisms of placental transfer, we used an in situ rat placental perfusion model. Fourteen Sprague-Dawley rats that were 20 days pregnant were randomized to epidermal growth factor or placebo during placental transport experiments. We chose ethylenediaminetetraacetate tagged with chromium 51 as a marker of placental permeability. Epidermal growth factor treatment led to a dramatic increase of maternofetal clearances of chromium 51 ethylenediaminetetraacetate. We conclude that maternally administered epidermal growth factor has a potent action on placental permeability. PMID- 1906682 TI - Effect of clomiphene citrate treatment on endometrial estrogen and progesterone receptor induction in women. AB - A direct adverse effect of clomiphene citrate on the endometrium has been presumed, and interference with estrogen receptor-mediated endometrial estrogen receptor and progesterone receptor induction has been implicated as the mechanism responsible for an increased incidence of luteal phase deficiency in association with clomiphene citrate treatment. To clarify the net influence of clomiphene administration on endometrial steroid receptor induction, we studied five normal ovulatory women, in both a spontaneous and clomiphene-induced (150 mg/day, cycle days 5 to 9) ovulatory cycle. From cycle day 11 blood samples were obtained daily and urinary luteinizing hormone determinations were performed twice daily. Endometrial biopsy was performed on the day of the urinary luteinizing hormone surge and again 13 days after the surge. Serum levels of follicle-stimulating hormone and luteinizing hormone were determined by immunoradiometric assay, estradiol and progesterone by radioimmunoassay, and clomiphene citrate isomer concentrations in treatment cycles by reversed-phase high-performance liquid chromatography and fluorescence detection. Total, cytosolic, and salt-extracted nuclear endometrial estrogen receptor and progesterone receptor concentrations were determined by enzyme-linked immunoassay. Serum estradiol was threefold to fivefold higher (p less than 0.05) in clomiphene-induced than in spontaneous cycles 8 and 10 days before the luteinizing hormone surge, and progesterone was increased (p less than 0.05) from the day of the surge to end of the cycle. Serum enclomiphene rose to plateau between 12 and 6 days before the luteinizing hormone surge (4.1 +/- 0.8 ng/ml, mean +/- SE, n = 19) and fell thereafter to less than 1.0 ng/ml. Zuclomiphene levels increased rapidly between 14 and 8 days before the surge (53.9 +/- 2.8 ng/ml, mean +/- SE, n = 5) and then decreased gradually but remained elevated throughout the luteal phase (29.0 +/- 1.2 ng/ml, mean +/- SE, n = 33). Late luteal endometrial histology was abnormal in one of four available treatment cycle specimens, but the endocrine characteristics and number and subcellular distribution of estrogen receptor and progesterone receptor in the abnormal cycle were not different from those of normal, in-phase cycles.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1906683 TI - Costs and benefits of examining all placentas. PMID- 1906684 TI - Genetic control of susceptibility to diethylnitrosamine and dimethylbenzanthracene carcinogenesis in rats. AB - The susceptibility to cancer induction after a single dose of diethylnitrosamine in male rats and a single dose of dimethylbenzanthracene in female rats was examined in the grc- strain R16 and the grc+ strain ACP, both of which have the same major histocompatibility complex genes but differ in the grc region. No tumor-promoting regimens were used, and the animals were fed only laboratory chou. The R16 males developed liver cancer and the R16 females developed breast cancer, there also were malignancies in other organs in some animals. By contrast, the ACP males did not develop any malignancies, and the ACP females had a significantly lower prevalence of malignant tumors. Thus the susceptibility to cancer in these two strains of rats has a genetic basis associated with genes in the grc region, and is independent of the carcinogen used, the action of a promoter, and the sex of the animals. PMID- 1906685 TI - Bupropion, ECT, and dopaminergic overdrive. PMID- 1906686 TI - International collaboration in a cluster investigation. PMID- 1906687 TI - Facile detection of anatoxin-a in algal material by thin-layer chromatography with Fast Black K salt. AB - A method for facile high-capacity screening of algal samples for anatoxin-a (ANTX a), a potent neurotoxin of Anabaena flos-aquae, is presented. The method is based on in situ colour reaction of algal extracts containing ANTX-a on a thin-layer chromatographic plate with the diazonium reagent Fast Black K salt, and subsequent separation of the orange-red product. The product, shown to be a stable 3,3-dialkyltriazene, is derived from a reaction involving the aliphatic secondary amino group of ANTX-a. The detection limit for ANTX-a is 10 micrograms g-1 of lyophilized algal material, which is comparable to earlier methods using more complex instrumentation. PMID- 1906688 TI - Endrate or Amidate. PMID- 1906689 TI - [Obstetrical anesthesia of patients with disseminated lupus erythematosus]. AB - The anaesthetic management of pregnant women who suffered from systemic lupus erythematosus (SLE) was reviewed retrospectively. During the ten-year period studied, there were nineteen pregnancies in eighteen women (mean age 27 years) who had either SLE or an isolated lupus type anticoagulant (LAF). Four pregnancies were stopped before the third trimester, two spontaneously, and the other two because of the mother's condition. Of the fifteen remaining pregnancies, eight children were born with a weight less than 2,500 g. One child, birth weight 750 g, died after three days. None of the fourteen living children had neonatal lupus. Six epidural and twelve general anaesthetics were carried out for four abortions, nine Caesarian sections, and five deliveries. Epidural anaesthesia was often contraindicated by neurological and haemostatic complications of the SLE: recent meningitis, thrombocytopaenia, prolonged bleeding, anticoagulant therapy. In fact, management of SLE patients required extensive preanaesthetic clinical and paraclinical assessment, as all the systems may be involved in this condition; moreover, it may worsen during pregnancy (seven times in this series). The most frequent complications were cardiovascular, renal, and haematological. Possible intubation difficulties must also be looked for. A LAF was associated with a great number of venous thromboses. An isolated LAF does not contraindicate epidural anaesthesia, as long as there is no associated haemostatic defect, such as a thrombocytopaenia. Furthermore, the patient should not have had prolonged episodes of unexplained bleeding, or require anticoagulants. In the present series, epidural anaesthesia was contraindicated in three of the four patients with LAF. Finally, prevention of thromboembolism, postoperative infection and adrenal failure (in those patients with long-term steroid therapy) must be carried out. PMID- 1906690 TI - Bleeding complications following initiation of thrombolytic therapy for acute myocardial infarction: a comparison of helicopter-transported and nontransported patients. AB - STUDY OBJECTIVE: To evaluate the effect of helicopter transport of acute myocardial infarction (AMI) patients after initiation of thrombolysis on bleeding complications through hospital discharge. DESIGN: Prospectively identified incidence (cohort) study. SETTING: Air medical service of tertiary-care teaching hospital. TYPES OF PARTICIPANTS: Ninety-five consecutive AMI patients transported within 12 hours of the initiation of thrombolysis with recombinant tissue-type plasminogen activator were compared with 119 nontransported AMI patients treated in a similar manner. RESULTS: The transported and nontransported populations were similar with regard to age, sex, and infarct location. Transport was well tolerated with no episodes of cardiac arrest or cardioversion occurring during transport. Hypotension requiring fluids or increased pressors occurred in 18 patients. Bleeding complications of all types occurred in 43.2% of the transported and 49.6% of the nontransported patients, respectively (relative risk, 0.87; 95% confidence interval, 0.65 to 1.17). CONCLUSION: Helicopter transport of AMI patients after initiation of thrombolysis appears to be safe acutely and without a clinically significant increase in risk of bleeding complications through hospital discharge when accomplished by a highly skilled team. PMID- 1906691 TI - Cardiovascular effects of halothane anesthesia after diazepam and ketamine administration in beavers (Castor canadensis) during spontaneous or controlled ventilation. AB - Fourteen adult beavers (Castor canadensis) weighing 16.5 +/- 4.14 kg (mean +/- SD) were anesthetized for surgical implantation of radio telemetry devices. Beavers were anesthetized with diazepam (0.1 mg/kg) and ketamine (25 mg/kg) administered IM, which provided smooth anesthetic induction and facilitated tracheal intubation. Anesthesia was maintained with halothane in oxygen via a semiclosed circle anesthetic circuit. Values for heart rate, respiratory rate, esophageal temperature, direct arterial blood pressure, end-tidal halothane concentration, and end-tidal CO2 tension were recorded every 15 minutes during the surgical procedure. Arterial blood samples were collected every 30 minutes to determine pH, PaO2, and PaCO2. Values for plasma bicarbonate, total CO2, and base excess were calculated. Ventilation was spontaneous in 7 beavers and controlled to maintain normocapnia (PaCO2 approx 40 mm of Hg) in 7 others. Vaporizer settings were adjusted to maintain a light surgical plane of anesthesia. Throughout the surgical procedure, all beavers had mean arterial pressure less than 60 mm of Hg and esophageal temperature less than 35 C. Mean values for arterial pH, end-tidal CO2, PaO2, and PaCO2 were significantly (P less than 0.05) different in spontaneously ventilating beavers, compared with those in which ventilation was controlled. Respiratory acidosis during halothane anesthesia was observed in spontaneously ventilating beavers, but not in beavers maintained with controlled ventilation. All beavers recovered unremarkably from anesthesia. PMID- 1906693 TI - Fulminant hepatic failure associated with 2',3'-dideoxyinosine (ddI). PMID- 1906692 TI - Hemorrhagic events during therapy with recombinant tissue-type plasminogen activator, heparin, and aspirin for acute myocardial infarction. Results of the Thrombolysis in Myocardial Infarction (TIMI), Phase II Trial. AB - OBJECTIVES: To assess the effects of invasive procedures, hemostatic and clinical variables, the timing of beta-blocker therapy, and the doses of recombinant plasminogen activator (rt-PA) on hemorrhagic events. DESIGN: A multicenter, randomized, controlled trial. SETTING: Hospitals participating in the Thrombolysis in Myocardial Infarction, Phase II trial (TIMI II). INTERVENTIONS: Patients received rt-PA, heparin, and aspirin. The total dose of rt-PA was 150 mg for the first 520 patients and 100 mg for the remaining 2819 patients. Patients were randomly assigned to an invasive strategy (coronary arteriography with percutaneous angioplasty [if feasible] done routinely 18 to 48 hours after the start of thrombolytic therapy) or to a conservative strategy (coronary arteriography done for recurrent spontaneous or exercise-induced ischemia). Eligible patients were also randomly assigned to either immediate intravenous or deferred beta-blocker therapy. MEASUREMENTS: Patients were monitored for hemorrhagic events during hospitalization. MAIN RESULTS: In patients on the 100 mg rt-PA regimen, major and minor hemorrhagic events were more common among those assigned to the invasive than among those assigned to the conservative strategy (18.5% versus 12.8%, P less than 0.001). Major or minor hemorrhagic events were associated with the extent of fibrinogen breakdown, peak rt-PA levels, thrombocytopenia, prolongation of the activated partial thromboplastin time (APTT) to more than 90 seconds, weight of 70 kg or less, female gender, and physical signs of cardiac decompensation. Immediate intravenous beta-blocker therapy had no important effect on hemorrhagic events when compared with delayed beta-blocker therapy. Intracranial hemorrhages were more frequent among patients treated with the 150-mg rt-PA dose than with the 100-mg rt-PA dose (2.1% versus 0.5%, P less than 0.001). The extent of the plasmin-mediated hemostatic defect was also greater in patients receiving the 150-mg dose. CONCLUSIONS: Increased morbidity due to hemorrhagic complications is associated with an invasive management strategy in patients with acute myocardial infarction. Our findings show the complex interaction of several factors in the occurrence of hemorrhagic events during thrombolytic therapy. PMID- 1906694 TI - Induction of beta-lactamase production in Pseudomonas aeruginosa biofilm. AB - Imipenem induced high levels of beta-lactamase production in Pseudomonas aeruginosa biofilms. Piperacillin also induced beta-lactamase production in these biofilms but to a lesser degree. The combination of beta-lactamase production with other protective properties of the biofilm mode of growth could be a major reason for the persistence of this sessile bacterium in chronic infections. PMID- 1906695 TI - Invalidity for Pseudomonas aeruginosa of an accepted model of bacterial permeability to beta-lactam antibiotics. AB - The accepted model for the penetration of beta-lactam antibiotics into gram negative bacteria is that proposed by Zimmermann and Rosselet (Antimicrob. Agents Chemother. 12:368-372, 1977). The model assumes (i) that diffusion of the antibiotic molecules across the outer membrane obeys Fick's law and can be characterized by a permeability constant for any given combination of organism and drug, (ii) that drug hydrolysis within the periplasm obeys Michaelis-Menten kinetics, and (iii) that a steady state is rapidly attained between drug uptake and hydrolysis. The model has allowed accurate prediction of antibiotic MICs for Escherichia coli strains from a knowledge of their beta-lactamase production and permeability characteristics. It has been suggested that the model is inappropriate for Pseudomonas aeruginosa, but attempts to confirm this have been bedevilled by experimental difficulties in estimating permeability coefficients for this species. In the present study, we tested a prediction of the model that the overall resistance of P. aeruginosa transconjugants containing a plasmid encoded beta-lactamase should continue to depend partly on permeability. Transconjugants with PSE-4 beta-lactamase were constructed in host strains with widely different levels of intrinsic, presumably impermeability-determined resistance. Contrary to the prediction of the model, all the transconjugants developed identical overall levels of resistance to substrate beta-lactams, such as azlocillin and cefoperazone, irrespective of the initial levels of intrinsic resistance of the recipient strains. We conclude that the model is inappropriate for P. aeruginosa, and possible explanations for the organism's behavior are discussed. PMID- 1906696 TI - In vitro activities of sparfloxacin, tosufloxacin, ciprofloxacin, and fleroxacin. AB - The in vitro activity of sparfloxacin was compared with those of tosufloxacin, ciprofloxacin, and fleroxacin against 730 bacterial isolates representing 49 different species. Sparfloxacin and ciprofloxacin had similar spectra of activity, but sparfloxacin was less active against Pseudomonas aeruginosa and more active against many gram-positive cocci and anaerobic bacteria. Tosufloxacin MICs were generally 8- to 16-fold lower than those for sparfloxacin or ciprofloxacin. All four fluoroquinolones were active against nalidixic acid susceptible strains of the family Enterobacteriaceae (MIC for 90% of the isolates [MIC90], less than or equal to 0.25 micrograms/ml) but nalidixic acid-resistant strains were less susceptible (MIC90, greater than or equal to 4.0 micrograms/ml). Against Pseudomonas aeruginosa isolates, MIC90s were 1.0 micrograms/ml for tosufloxacin, 2.0 micrograms/ml for ciprofloxacin, and 4.0 micrograms/ml for sparfloxacin. Against Enterococcus faecalis, sparfloxacin and ciprofloxacin MIC90s were 1.0 and 2.0 micrograms/ml, respectively. MIC90s for ciprofloxacin-susceptible Staphylococcus aureus were 0.016 micrograms/ml for tosufloxacin, 0.06 micrograms/ml for sparfloxacin, and 0.5 micrograms/ml for both ciprofloxacin and fleroxacin. With four species of gram-negative bacilli, mutants resistant to two to four times the sparfloxacin MIC occurred spontaneously at frequencies of 10(-7) to 10(-9): single-step high-level resistance was not observed. In vitro-selected sparfloxacin-resistant mutants displayed cross resistance to other quinolones, as did clinical isolates of ciprofloxacin resistant S. aureus. Tosufloxacin MICs with broth microdilution methods were four to eightfold greater than those obtained with agar dilution methods. The two procedures gave comparable results when sparfloxacin or ciprofloxacin was being tested. PMID- 1906697 TI - Behavior of Listeria monocytogenes inoculated into raw tomatoes and processed tomato products. AB - Rates of death and growth of Listeria monocytogenes inoculated onto raw whole and into chopped tomatoes stored at 10 and 21 degrees C were not influenced by prior treatment of tomatoes with chlorine or packaging under an atmosphere of 3% O2 and 97% N2. Growth of the pathogen occurred in whole tomatoes held at 21 degrees C but not at 10 degrees C, while death occurred in chopped tomatoes stored at these temperatures. Likewise, growth patterns of mesophilic aerobic microorganisms, psychrotrophic microorganisms, and yeasts and molds on whole and chopped tomatoes were essentially unaffected by chlorine and modified atmosphere packaging treatments. Populations of L. monocytogenes inoculated into commercially processed tomato juice and sauce and held at 5 degrees C remained constant for 14 days. A gradual decrease in the number of viable L. monocytogenes cells was observed in juice and sauce held at 21 degrees C. In contrast, the organism died rapidly when suspended in commercial tomato ketchup at 5 and 21 degrees C. Unlike low-acid raw salad vegetables such as lettuce, broccoli, asparagus, and cauliflower on which we have observed L. monocytogenes grow at refrigeration temperatures, tomatoes are not a good growth substrate for the organism. Nevertheless, L. monocytogens can remain viable on raw whole and chopped tomatoes and in commercial tomato juice and sauce for periods extending beyond their normal shelf-life expectancy. PMID- 1906698 TI - Influence of CO2 and low concentrations of O2 on fermentative metabolism of the ruminal ciliate Polyplastron multivesiculatum. AB - The effects of ruminal concentrations of CO2 and oxygen on the end products of endogenous metabolism and fermentation of D-glucose by the ruminal entodiniomorphid ciliate Polyplastron multivesiculatum were investigated. The principal metabolic products were butyric, acetic, and lactic acids, H2, and CO2. 13C nuclear magnetic resonance spectroscopy identified glycerol as a previously unknown major product of D-[1-13C]glucose fermentation by this protozoan. Metabolite formation rates were clearly influenced by the headspace gas composition. In the presence of 1 to 3 microM O2, acetate, H2, and CO2 formation was partially depressed. A gas headspace with a high CO2 content (66 kPa) was found to suppress hydrogenosomal pathways and to favor butyrate accumulation. Cytochromes were not detected (less than 2 pmol/mg of protein) in P. multivesiculatum; protozoal suspensions, however, consumed O2 for up to 3 h at 1 kPa of O2. Under gas phases of greater than 2.6 kPa of O2, the organisms rapidly became vacuolate and the cilia became inactive. The results suggest that fermentative pathways in P. multivesiculatum are influenced by the O2 and CO2 concentrations that prevail in situ in the rumen. PMID- 1906699 TI - Behavior of Listeria monocytogenes in wiener exudates in the presence of Pediococcus acidilactici H or pediocin AcH during storage at 4 or 25 degrees C. AB - Exudative fluids were collected from packages of five brands of all-beef wieners and inoculated to contain 10(4) to 10(5) CFU of a three-strain (Scott A, V7, and 101M) mixture of Listeria monocytogenes per ml. Listeriae were inactivated (decrease of 0.61 to 3.8 log10 CFU/ml) in all five exudates held at 4 degrees C for 29 days. L. monocytogenes grew (increase of 1.7 to 3.6 log10 CFU/ml) in two of five exudates held at 25 degrees C for 6 days. Exudate was inoculated with a derivative of Pediococcus acidilactici H (designated JBL1095) or treated with pediocin AcH (a bacteriocin) as a novel approach to control the growth of L. monocytogenes in wiener exudates. Initially, pediocin AcH caused rapid death (decrease of 0.74 log10 CFU/ml in 2 h) of L. monocytogenes in exudate held at 4 degrees C, but thereafter the inactivation was similar to that in control exudate (L. monocytogenes only) or exudate containing L. monocytogenes plus JBL1095. At 25 degrees C, L. monocytogenes grew in the presence of JBL1095 during the first 64 h of incubation, but thereafter the numbers of the pathogen decreased appreciably (5.84 log10 CFU/ml in 3 days). In the presence of pediocin AcH, there was a gradual decrease in numbers of L. monocytogenes throughout the storage period at 25 degrees C. These data indicate that added biopreservatives can potentiate and amplify the intrinsic listeriostatic or listericidal activity of wiener exudate. PMID- 1906700 TI - Behavior of Listeria monocytogenes during fabrication and storage of experimentally contaminated smoked salmon. AB - Experiments were carried out to examine the behavior of Listeria monocytogenes in the course of fabrication and storage of smoked salmon. In three trials, raw salmon fillets were surface inoculated with L. monocytogenes, marinated, smoked at 26 to 30 degrees C, and stored at 4 or 10 degrees C for up to 30 days. At different times during the fabrication and storage, samples were taken and, by means of the three-tube most probable number (MPN) method, quantitatively analyzed for the concentration of L. monocytogenes. The initial Listeria levels in the raw fillets were 10(4) MPN/g in trial 1, 10(1) MPN/g in trial 2, and 10(2) MPN/g in trial 3. During the fabrication, neither an increase nor a decrease of the inoculated quantities was observed. During the storage, however, a significant growth was measured in two of three trials; in trial 1, a 2.5 log10 MPN/g increase and in trial 3, an increase of even 4.5 log10 MPN/g. In the second trial, the Listeria level remained about the same. The results indicate the importance of preventing pre- and postprocessing contamination of L. monocytogenes in raw and smoked salmon. Because a significant increase of L. monocytogenes was measured during storage, there might be an increasing risk of infection for the consumer by storing such fish for a long time. PMID- 1906701 TI - [Pharmacokinetic approach to the improvement of clinical predictability in the preclinical test for antitumor agents]. AB - Clinical predictability of preclinical test for antitumor agents has not been significantly improved even after the use of a human tumor/nude mouse model. Such different antitumor activities between preclinical and clinical tests probably due to the fact that therapeutic used in both tests usually each maximum tolerated dose (MTD), are pharmacokinetically not equivalent. Therefore, we introduced a new concept of "clinically equivalent dose (CED)", which can reproduce in the nude mouse the blood level of a given drug observed with human patients received its therapeutic dose. Treatment of human tumors implanted in the nude mice with CEDs of several drugs exhibited much better correlation with their clinical efficacies than those with MTDs. The feasibility of use of CED predicted by animal scale-up procedure as a therapeutic dose in the preclinical test was discussed. PMID- 1906702 TI - Imidazo[4,5-b]pyridine derivatives of potential tuberculostatic activity. Part 1: Synthesis and quantitative structure-activity relationships. AB - New derivatives of imidazo[4,5-b]pyridine and 9H-dipyrido-[1,2-a:3',2' d]imidazole were synthesized. Antibacterial activity against Mycobacterium tuberculosis of selected compounds was determined. These data were combined with the corresponding bioactivity data previously generated for two other series of imidazo[4,5-b]pyridines. Analysis of Quantitative Structure-Activity Relationships [QSAR] was carried out using nonempirical structural descriptors. Hydrophobicity of the agents studied was found decisive for their activity. A QSAR equation was derived allowing rational design of active derivatives. PMID- 1906703 TI - Short-bowel syndrome in children. Quality of life in an era of improved survival. AB - A number of disorders in childhood can result in short-bowel syndrome (small bowel length, less than 100 cm). Improved care has increased survival in patients with short-bowel syndrome, but the quality-of-life factors associated with such improved survival have not been examined, to our knowledge. Sixteen consecutive pediatric patients with short-bowel syndrome (bowel length range, 22 to 98 cm) were followed up for 2 to 10 years. The original diagnoses were as follows: necrotizing enterocolitis (n = 6), multiple intestinal atresias (n = 4), extensive aganglionosis (n = 2), meconium peritonitis (n = 2), and midgut volvulus (n = 2). The range of initial hospitalization was from 62 to 395 days, and 13 of 16 patients have required readmission (two to 14 times). All patients required multiple operations (range, two to 14 operations), including combinations of venous access, adhesiolysis, tapering enteroplasty, reversed intestinal segments, and pull-through procedure. Nine of 16 patients received home total parenteral nutrition, and 12 of 16 patients required home elemental diets, usually via pump feedings. Fifteen patients (94%) survived. Two survivors are deaf, and one of these has mild developmental delay. Seven survivors (age range, 6 to 10 years) attend a regular school, four while receiving total parenteral nutrition or an elemental diet. Ten of 15 survivors are off all nutritional support (including the child with a 22-cm small bowel), with four others weaning. The presence or absence of an ileocecal valve did not affect outcome. Modern nutritional support methods provide excellent survival and quality of life for children with short-bowel syndrome. PMID- 1906704 TI - [Analysis of the regulation of IgG production to Cryptomeria japonica pollen antigen]. AB - Genetic control of the immune response to Cryptomeria japonica pollen antigen (CPAg) in humans was analyzed using 72 unrelated healthy adults. The 72 were classified into a low responder group and a high responder group by using purified CPAg. Significant associations were found between IgG low responsiveness to purified CPAg and possession of HLA-DQw3. Relative risks for the two groups were 4.80. Peripheral blood lymphocytes from low responders revealed a specific IgG response to CPAg when the CD8+ T cell fraction was depleted. Thereby, low response due to the presence of CPAg-specific CD8+ suppressor T cells was suggested. PMID- 1906705 TI - [Use of personal protective equipment by pathologists and legal physicians working with particularly dangerous infectious diseases]. AB - The possibility of pneumosuit use constructed in the Institute to protect the pathology department staff at the hospitals for infectious diseases from HIV virus was studied. The suit is a hose-type suit for protection of respiratory organs and skin using the ventilated underhood space and autonomic air supply. Both the detailed description of this suit and its disinfection scheme developed and tested by authors are presented. The comparative physio-hygienic assessment of pneumosuit and standard antiplaque suit demonstrated a number of advantages of the former during 2 hours work at pathology department. The authors recommend the pneumosuit as an equipment for the protection of skin and respiratory organs of pathologists and legal physicians working with particularly dangerous infections. PMID- 1906706 TI - Childhood infectious diseases and immunisations update. AB - The author concentrates on the current childhood immunisation schedule, and on those preventable childhood infections that are still common. He also focuses on their incubation periods and on their infectivity. PMID- 1906707 TI - Insulin stopwork. PMID- 1906708 TI - Proteoglycans synthesized by an osteoblast-like cell line (UMR 106-01). AB - The proteoglycans synthesized by an osteoblast-like cell line of rat origin (UMR 106-01) were defined after biosynthetic labelling with [35S]sulphate and [3H]glucosamine. Newly synthesized labelled proteoglycans were characterized by differential enzymic digestion in combination with analytical gel filtration and SDS/PAGE. UMR 106-01 cells were found to synthesize three major species of proteoglycan: a large chondroitin sulphate proteoglycan of Mr approximately 1 x 10(6), with a core protein of Mr approximately 350,000-400,000; a small chondroitin sulphate-containing species of Mr approximately 120,000 with a core protein of Mr 43,000; and a heparan sulphate proteoglycan of Mr approximately 150,000, with a core protein of Mr approximately 80,000. Over 70% of the newly synthesized intact proteoglycan species are associated with the cell layer of near-confluent cells; however, accessibility to trypsin digestion suggests an extracellular location. Chemical characteristics of the proteoglycans and preliminary mRNA hybridization indicate that the small chondroitin sulphate proteoglycan is probably PG II (decorin). The large chondroitin sulphate proteoglycan is most likely related to a hyaluronate-aggregating species from fibroblasts (versican), and the heparan sulphate proteoglycan bears striking similarities to cell-membrane-intercalated species described for a number of cell types. PMID- 1906709 TI - Asparagine-linked glycoprotein biosynthesis in rat epididymis. Presence of a mannosidase II-like enzyme. AB - Previous studies from this laboratory using p-nitrophenyl alpha-D-mannoside (p NPM) as substrate provided no evidence for the presence of mannosidase II in the rat epididymis [Skudlarek & Orgebin-Crist (1988) J. Reprod. Fertil. 84, 611-617]. However, rat epididymal epithelial cells cultured in the presence of swainsonine, an inhibitor of mannosidase II, produce abnormally processed N-linked glycoproteins containing hybrid-type oligosaccharides instead of complex-type [Tulsiani, Skudlarek & Orgebin-Crist (1990) Biol. Reprod. 43, 130-138], a result providing indirect evidence for the presence of mannosidase II-like enzyme in rat epididymis. In the studies described here, we present evidence for the occurrence of this processing enzyme in rat epididymal Golgi membranes. This enzyme is an integral Golgi membrane component. Like liver mannosidase II, the epididymal enzyme cleaves alpha 1,3- and alpha 1,6-linked mannosyl residues from GlcNAcMan5GlcNAc. However, unlike liver mannosidase II, the epididymal enzyme shows no activity towards the synthetic substrate, p-NPM. The epididymal mannosidase cross-reacts with liver anti-(mannosidase II) antibody, a result suggesting that the two enzymes share a common antigenic site(s). Immunoblotting studies following resolution of liver and epididymal Golgi membranes on SDS/PAGE show that, whereas the liver mannosidase II was resolved as a doublet of Mr 120,000 and 122,000, only the Mr 120,000 band was observed in the epididymal Golgi membranes. Immunoblotting of the Golgi-rich fractions, resolved under non denaturing conditions, showed different patterns of charge and/or size isomers from the two tissues. These studies demonstrate tissue-specific differences in processing enzymes with similar function. PMID- 1906710 TI - Failure of [32P]ADP-ribosylation by pertussis toxin to determine Gi alpha content in membranes from various human tissues. Improved radioimmunological quantification using the 125I-labelled C-terminal decapeptide of retinal transducin. AB - The quantitative determination of pertussis-toxin-sensitive guanine-nucleotide binding proteins (G-proteins) in cell membranes is still a problem. Pertussis toxin-catalysed [32P]ADP-ribosylation strongly relies on the substrate quality of the alpha-subunits and is influenced by the concentration of nucleotides, beta gamma-subunits, the physicochemical properties of the membranes influencing the availability of Gi alpha for pertussis toxin, and covalent modification of Gi alpha. Quantification of immunoreactive material on Western blots can be only imprecisely performed by two-dimensional densitometry. In order to generate a method for quantification of pertussis-toxin-sensitive G-proteins in membranes we have developed a fast and sensitive radioimmunoassay. The C-terminal decapeptide of retinal transducin alpha (KENLKDCGLF) was 125I-labelled and used as tracer. Polyclonal antiserum (DS 4) was raised against this peptide. Gi alpha proteins were determined by competition of solubilized membranes for 125I-KENLKDCGLF binding to DS 4 using dilutions of retinal transducin alpha as standard. The interassay variation was less than 10%, with a sensitivity of 2.5 micrograms/ml. The density of Gi alpha was highest in human adipose tissue, followed by HL60 cells, lung, mononuclear leucocytes, thrombocytes and left ventricular myocardium. A striking difference was observed between the density of Gi alpha and the amount of incorporation of [32P]ADP-ribose into the 40 kDa membrane proteins by pertussis toxin in the same samples. This is also demonstrated by comparison of the weak [32P]ATP-ribosylation of pertussis toxin substrates with the density of immunoreactive Gi alpha on Western blots in tissues such as lung. This study shows that the Gi alpha content can be exactly determined by a sensitive and fast radioimmunoassay using iodinated synthetic peptide homologues of Gi alpha proteins. Radioimmunological quantification of Gi alpha might be able to detect the 'true' Gi alpha content of membranes without being hampered by influences on the [32P]ADP-ribosylation reaction. It is concluded that this newly developed method may become an important tool for studying expression of Gi alpha proteins in a variety of tissues or cell types, and for precisely quantifying the changes caused by pathological conditions. PMID- 1906711 TI - Structural and functional characterization of Factor VIII-delta II, a new recombinant Factor VIII lacking most of the B-domain. AB - A recombinant Factor VIII (Factor VIII-delta II) consists of a unique polypeptide chain of 165 kDa deleted from the major part of the B-domain and from the cleavage site at Arg-1648-Glu-1649 found in plasma-derived Factor VIII. It was expressed in mammalian cells in serum-free medium containing von Willebrand factor and purified by a one-step immunopurification. The recombinant Factor VIII was characterized as a single active peak when subjected to f.p.l.c., in contrast with the plasma-derived molecule. Its coagulant activity was decreased in the presence of EDTA, suggesting that a bivalent ion is required, as for plasma derived Factor VIII. The activation by thrombin and the inactivation by activated protein C were studied and the resulting molecular forms were analysed by f.p.l.c. and SDS/PAGE. The results clearly demonstrate that, despite the structural differences between plasma-derived and recombinant Factor VIII, activation and inactivation of Factor VIII-delta II generate proteolysed complexes similar to that described for plasma-derived Factor VIII. Thus this deleted recombinant Factor VIII, which is processed similarly to plasma-derived Factor VIII, should be normally integrated in the regulation system of Factor X activation in the blood-coagulation cascade. PMID- 1906712 TI - Agonist-induced Ca2+ influx in human neutrophils is secondary to the emptying of intracellular calcium stores. AB - Emptying of the intracellular calcium stores of human neutrophils, by prolonged incubation in Ca(2+)-free medium, by treatment with low concentrations of the Ca2+ inophore ionomycin, or by activation with cell agonists, increased the plasma-membrane permeability to Ca2+ and Mn2+. The chemotactic peptide formylmethionyl-leucyl-phenylalanine and the natural agonists platelet-activating factor and leukotriene B4 released different amounts of calcium from the stores and induced Ca2+ (Mn2+) uptake, the rate of which correlated inversely with the amount of calcium left in the stores. The increased Mn2+ uptake induced by these agonists was persistent in cells incubated in Ca(2+)-free medium, but returned to basal levels in cells incubated in Ca(2+)-containing medium, with the same time course as the refilling of the calcium stores. The calcium-stores-regulated Mn2+ influx, including that induced by agonists, was prevented by cytochrome P-450 inhibitors. We propose that agonist-induced Ca2+ (Mn2+) influx in human neutrophils is secondary to the emptying of the intracellular stores which, in turn, activates plasma-membrane Ca2+ channels by a mechanism involving microsomal cytochrome P-450, similar to that described previously in thymocytes [Alvarez, Montero & Garcia-Sancho (1991) Biochem. J. 274, 193-197]. PMID- 1906713 TI - Differential role of apolipoprotein AI-containing particles in cholesterol efflux from adipose cells. AB - Cholesterol efflux was studied in cultured Ob1771 adipose cells after preloading with LDL cholesterol. Exposure to particles containing apo AII (LpAI) and particles containing apo AI and apo AII (LpAI:AII) isolated from native human plasma, and from HDL2 or HDL3, showed that only LpAI were able to promote cholesterol efflux, despite the fact that both kinds of particles were able to bind to receptor sites within the same range of concentrations (apparent Kd values between 10 and 25 micrograms/ml). During this long-term exposure, LpAI:AII demonstrated a concentration-dependent inhibition (10-60 micrograms/ml) of LpAI mediated cholesterol efflux from adipose cells under conditions where LpAI:AII did not deliver cholesterol to the cells and where no net change in the distribution of apo AI between LpAI and LpAI:AII was observed. The antagonizing and modulating role of LpAI:AII in preventing cholesterol efflux mediated by LpAI appears not to be related to the lipid composition and cholesterol content of the particles but, rather, appears dependent upon the presence of apo AI in LpAI particles and apo AII in LpAI:AII particles. The actual concentrations of these particles in the interstitial fluid bathing peripheral cells might be critical for the in vivo occurrence of cholesterol efflux. PMID- 1906715 TI - Solvent abuse, toluene acidosis and diabetic ketoacidosis. AB - Solvent abuse in adolescents and young adults has been reported to cause a metabolic acidosis with a normal or increased anion gap (Streicher et al., 1981; Voights & Kaufman, 1983, Anonymous, 1988). We report a particularly severe clinical problem produced by the combination of toluene intoxication and diabetic ketoacidosis. PMID- 1906714 TI - Variation at the apo AI/CIII/AIV gene complex is associated with elevated plasma levels of apo CIII. AB - A number of studies have reported that a variant allele (S2) of the apo AI/CIII/AIV complex is associated with high plasma lipid levels in some populations and furthermore that the frequency of this allele is 2-5-fold higher in patient groups with premature coronary heart disease compared to control groups. This study shows in the healthy "English" population that the S2 allele is associated with elevated plasma apo CIII levels but not with low apo AI levels. In addition, it shows that the allele is associated with elevated plasma levels of apo B in men. Regression analysis shows in both men and women that apo CIII levels are positively correlated with plasma triglyceride levels and moreover that they are a stronger predictor of this parameter than apo AI, B or AIV. Apo CIII levels are also an independent predictor of total plasma cholesterol and HDL-cholesterol levels in males and females, respectively. Together these data suggest that a genetic predisposition to develop elevated plasma levels of apo CIII, alone or in combination with elevated plasma apo AIV levels, is the primary defect responsible for the association of the S2 allele with hyperlipidemia and/or premature CHD. PMID- 1906716 TI - Physical properties and clinical efficacy of two sodium cromoglycate inhalation aerosol preparations. AB - In this study, the particle size distribution and the droplet characteristics of the delivered aerosol cloud were first determined for two disodium cromoglycate inhalation aerosol preparations obtained from different manufacturers. In addition, the in vitro deposition properties and the clinical efficacy of these preparations were compared. The evaluation of the in vitro deposition was performed using a cascade impactor. The clinical efficacy was monitored by measuring the peak expiratory flow (PEF) values after the exercise test in fifteen asthmatic patients. The particle size and the spray characteristics of these two inhalation aerosol preparations were similar; the results of the in vitro test confirmed their similar physical properties. Both disodium cromoglycate preparations clearly alleviated the bronchoconstriction after the exercise test. According to the results of the clinical trial, supported by the laboratory scale studies, both disodium cromoglycate aerosols are of equal value in asthma inhalation therapy. PMID- 1906717 TI - Pulpal pressure and bond strengths of SuperBond and Gluma. AB - The effects of storage under a simulated pulpal pressure on the shear bond strength of SuperBond and Gluma were evaluated using extracted, unerupted human teeth. Also evaluated was the effect of dentin position both vertically (i.e., superficial versus deep) and horizontally (center versus pulp horns) in the presence or absence of a pulpal pressure. Thirty-two cm of H2O pressure had no effect on the 24 hour shear bond strength of SuperBond C & B. There was also no significant difference in the bond strength of SuperBond to superficial versus deep dentin or central dentin versus dentin directly over pulp horns. The bond strengths of SuperBond ranged from 16.3-19.1 MPa. Gluma bonds were less than half as strong as those obtained with SuperBond C & B. Although there was no effect of dentin position on Gluma bond strength, in the presence of a pulpal pressure, the strength of the bonds fell in deep dentin especially over pulp horns. This testing protocol may prove of value in screening new dentin bonding systems. PMID- 1906718 TI - Microleakage of Class II silver glass ionomer/composite restorations. AB - This in vitro study examined the marginal integrity of Class II lesions using three restorative techniques. Class II preparations (MO and DO) were placed in 30 teeth. Half had the cervical margin placed 1 mm below the CEJ, the remaining had cervical margins 2 mm above the CEJ. The preparations were randomly restored using three techniques: 1) Glass ionomer liner and posterior composite resin; 2) Glass ionomer silver cermet placed in the proximal box to the contact area and the remainder restored with posterior composite resin; 3) Glass ionomer silver cermet only. All 30 teeth were loaded with 17 kg, thermocycled and stored in 37 degrees C solution for 30 days. The teeth were again loaded, immersed in 2% basic fuchsin solution for 24 hours, sectioned and photographed. Microleakage was calculated, according to the depth of dye penetration. Results demonstrated Techniques 1 and 2 to have less marginal leakage than Technique 3 when preparations remained in enamel and Techniques 1, 2 and 3 when preparations were below the CEJ. The chi-square test indicated a statistically significant difference between restoration technique and marginal microleakage (P less than 0.001). PMID- 1906719 TI - How long should patients with Salmonella typhi or Salmonella paratyphi be followed-up? A comparison of published guidelines. AB - Records were examined for 242 individuals infected with Salmonella typhi or S. paratyphi identified in Birmingham between 1981 and 1988, with a total of 335 person years of follow-up. Of these cases 77 and 78 per cent respectively were followed beyond the point at which surveillance would have ceased under guidelines published by the American Public Health Association and by the Public Health Laboratory Service for England and Wales. Under these two sets of guidelines only seven (3.8 per cent) and eight (4.3 per cent) cases respectively had subsequent positive faecal or urine cultures over a median of 335 and 295 days of additional follow-up. After 0, 1, 2, 3, 4 and 5 prior consecutive negative sets of cultures obtained at weekly intervals the likelihood of the next set of cultures being positive was 26, 9, 5, 2.2, 2.4 and 0 per cent respectively. Only 38 (1.7 per cent) of 2184 follow-up urine cultures were positive; these results did not influence duration of follow-up. Only 26 (2.6 per cent) of 1002 contacts were infected; the yields of the first, second and third sets of cultures were 1.5, 0.6 and 0.5 per cent respectively. PMID- 1906720 TI - Information needs in a provider market: a case-study of ENT. AB - In the light of the White Paper Working for patients, this study addresses two questions: first, whether the current pattern of service use is a valid surrogate for the assessment of the service needs of a population; second, given that information systems which will provide accurate cost per case information are several years from being implemented, what differences might be made to a specialty budget by the adjustment of case costs by use of different case-mix measures. ENT has been chosen as a case study because of its relative 'market potential'. The study addresses the first question by examining the variations in the current level and type of service use across Districts in a Region. The large variation in utilization across Districts, both in total and for different degrees of case complexity, suggests that the current pattern of service use is a poor indicator of need. The second part of the study examines a Unit which has large inflows of complex patients. Adjusting for case-mix, however, produces a comparatively small effect on the overall specialty budget, whether the adjustment is made using the BUPA schedule of surgical procedures or using diagnosis-related groups. In the light of these results, it is suggested that the current emphasis on accurately costing case-mix could be misplaced, and that more resources should be diverted to scrutinizing the appropriateness of service use to health needs and priorities, in line with the aims of the NHS reforms. PMID- 1906721 TI - Potential impacts on health of atmospheric change. PMID- 1906722 TI - Length of stay in general medical beds; implications for the NHS White Paper of variance within one performance indicator. AB - Data over several years have shown that the average length of stay in general medical beds in the Royal Preston Hospital is approximately 20 per cent above regional average. To investigate this we carried out a prospective study of 259 successive medical admissions to the hospital. We also carried out a retrospective study of routine data from the Korner episode system (KES) for the specialties of general medicine and geriatrics, using standardization techniques. After correcting for age and diagnostic group, the average length of stay in the hospital was close to the regional average. It is concluded that difference between districts in respect of age and diagnostic group can cause substantial difference in average length of stay. Future contracts between purchasing and providing health service authorities will need to take such difference into account if valid comparisons are to be made between two or more apparently similar alternatives. PMID- 1906723 TI - Serum sulfate concentration and the anion gap in hemodialysis patients. AB - First-of-the-month predialysis serum sulfate (SO4) and other blood chemistry values were measured prospectively for 5 to 7 months in 14 patients undergoing single pass chronic tri-weekly maintenance hemodialysis with bicarbonate dialysate. Blood was also obtained predialysis and again immediately postdialysis from seven patients (five of whom also participated in the chronic study). As expected, the patients manifested a high anion gap (AG) metabolic acidosis. Serum SO4 was only moderately stable from month to month (the average coefficient of variation was 0.30; correlation between the serum SO4 value of month one and months two and five were r = 0.59, p = 0.026; and r = 0.38, p = 0.182, respectively). The ratio of mean serum SO4 to mean AG (5.0 +/- 0.4 [SE] mEq/L divided by 19.1 +/- 0.5 mEq/L) was 0.26. Although there was a statistically significant correlation between the serum SO4 and the blood urea nitrogen (BUN), there was no such correlation between SO4 and AG. A single hemodialysis reduced serum SO4 by 54% (from 3.5 +/- 0.5 mEq/L to 1.6 +/- 0.1 mEq/L), but there was no correlation between the change in SO4 and the change in AG. The authors concluded that SO4 contributes importantly to the elevated AG in patients receiving chronic hemodialysis. Single pass bicarbonate hemodialysis temporarily reduces, but does not normalize, both the serum SO4 and the AG of such patients. PMID- 1906724 TI - In vivo distribution and cytokine gene expression by enriched mouse LAK effector cells. AB - Lymphokine activated killer (LAK) cells administered in combination with interleukin 2 (IL2) can mediate antitumor activity in tumor-bearing mice and advanced cancer patients. Relatively little is known about the mechanism by which adoptively transferred LAK cells plus IL2 mediate these antitumor effects in vivo, and it remains unclear to what extent the actual LAK effector cells can accumulate in tumors. In the present study, enriched cytolytic LAK effector cells were obtained by fractionation of bulk LAK cell cultures on Percoll density gradients. About 95% of the total lytic activity was recovered from the 55% of cells isolated in fraction 2 (Fr2). The cells recovered in Fr2 are mostly large, proliferating lymphoblasts that express either the NK-associated surface markers NK1.1 (38%) or LGL-1 (31%), or the cytotoxic T cell phenotype, Lyt2 (39%). The cytolytic lymphoblasts obtained from Fr2 were radiolabelled with either 111Indium Oxine (111InOx) which labels all cells in the population, or with 125Iododeoxyuridine (125IUdR) which labels only proliferating cells, and injected iv into mice bearing murine renal cancer (Renca). 111InOx-labeled Fr2 cells migrated mostly to spleen (28%) and liver (35%), with approximately 5% of the injected label detectable in the Renca-bearing kidney by 24 hrs. In contrast, Fr2 cells labeled with 125IUdR, which labels only the proliferating blasts thought to include the actual effector cells, exhibited a very different localization pattern. 125IUdR-Fr2 cells were retained in the lungs at higher levels than were 111InOx-Fr2 cells and very little label was detectable in liver (6%), spleen (3%), or tumor bearing kidney (2%) at 24 hrs. These results suggest that most of the large, proliferating lymphoblasts are cleared from the body by 24 hrs and very few localize into even large tumors. Subsequently, Northern blot analyses performed on bulk LAK cells revealed a potent induction of mRNA for TNF alpha by 6 hrs and for IFN gamma by 48 hrs. The intensity of gene expression for both cytokines was increased in Fr2 as compared to the unfractionated bulk LAK cells or to non-cytolytic cells obtained from Fr3. Overall, these results suggest that at least some of the antitumor effects mediated by LAK cells occur by the release of cytokines that synergize with exogenous IL2 for the activation of host effector cells. PMID- 1906725 TI - The synergistic effects of gamma interferon and clofazimine on phagocyte function: restoration of inhibition due to a 25 kilodalton fraction from Mycobacterium tuberculosis. AB - A 25 kDa glycolipoprotein from Mycobacterium tuberculosis has been shown to inhibit phagocyte functions associated with antimicrobial activity. These include the intracellular killing ability, reduction of nitro blue tetrazolium, hydrogen peroxide production and lysosyme release of polymorphonuclear leukocytes and peripheral blood monocytes. The present study undertook to investigate the synergistic effects of gamma interferon and clofazimine on restoring the inhibitory activities of the 25 kDa glycolipoprotein on these phagocyte functions. Gamma interferon and clofazimine at concentrations of 25 units/ml and 0.3 micrograms/ml acted synergistically by completely restoring all these systems. Independent use of these agents were unable to affect phagocyte functions or to restore the inhibition caused by the 25 kDa mycobacterial component. These studies indicate the possible use of these two phagocyte priming agents for the immunotherapy of tuberculosis. PMID- 1906726 TI - Randomised trial of epirubicin alone versus 5-fluorouracil, epirubicin and mitomycin C in locally advanced and metastatic carcinoma of the pancreas. AB - Sixty-nine unselected patients with locally advanced and metastatic carcinoma of the pancreas, who had not received previous chemotherapy or radiotherapy were randomised to receive either 5-fluorouracil, epirubicin and mitomycin C (FEM) or epirubicin. Survival was not significantly different in the two arms. Toxic reactions (WHO grade greater than 3) in the FEM and epirubicin arm respectively included nausea (2), (4), severe alopecia (1) (3) and leucopenia (1), (5), none of these were statistically significant. We therefore suggest that combination chemotherapy should not be used in preference to single agent chemotherapy as standard treatment for locally advanced or metastatic cancer of the pancreas. PMID- 1906727 TI - Increased epidermal growth factor receptor gene expression by gamma-interferon in a human breast carcinoma cell line. AB - The interferons are a group of naturally occurring proteins that inhibit the growth of tumours in vivo and many transformed cell lines in vitro. The mechanisms of action of interferon, however, remain unclear. The IFN induced inhibition of growth of many epithelial cancer cell lines is associated with changes in Epidermal Growth Factor Receptor (EGFR) binding or expression. Therefore, we examined the effect of IFN treatment on the expression of EGFR in a human breast carcinoma cell line, MDA 468. We have found the IFN-gamma inhibited, in a dose dependent fashion, the growth of MDA 468 cells. IFN decreased cell surface binding of 125I-EGF to EGFR by changing receptor number rather than affinity. However, total cellular receptor protein, as measured by immunoprecipitation with monoclonal antibodies, was increased in IFN-treated cells. The half-life of the metabolically labelled receptor was unchanged by treatment with IFN. Increased amounts of EGFR mRNA were observed in MDA 468 cells treated with IFN-gamma for 3 days. The levels of mRNA increased with time in culture, reaching a peak of four times control values after 5 days of treatment. This effect was observable with as little as 10 U ml-1 of IFN-gamma. Treatment of the cells with Actinomycin D to inhibit new RNA synthesis suggested that the stability of EGFR mRNA was not enhanced in IFN-gamma treated cells. The increase in receptor mRNA induced by IFN was not inhibited by cycloheximide. These data suggest IFN-gamma can increase expression of EGFR mRNA and protein in MDA 468 cells. Increased expression of EGFR mRNA and protein by IFN-gamma is associated with inhibition of cell growth. PMID- 1906728 TI - Effectiveness of isolated liver perfusion with mitomycin C in the treatment of liver tumours of rat colorectal cancer. AB - Dose limiting systemic toxicity prevents sufficient exploitation of the steep dose response relationship of most anticancer agents. In our rat liver tumour model (the CC531 colorectal carcinoma), isolated liver perfusion allows administration of higher doses of mitomycin C than hepatic artery infusion, while systemic toxicity remains minimal. To determine the temporal pattern of mitomycin C induced cytokinetic changes, we analysed flow cytometric DNA histograms of CC531 liver tumours from rats treated with high dose mitomycin C (3.2 mg kg-1) via hepatic artery infusion and sacrificed at different time intervals after treatment. Between 12 and 36 h after treatment, the fraction of cells in late S and G2/M phase had markedly increased. The effects of administration of the respective maximally tolerated doses of mitomycin C in isolated liver perfusion and via hepatic artery infusion on progression of tumour cells through the cell cycle and on gross tumour growth were compared. Isolated liver perfusion with mitomycin C resulted in a significant increase in the proportion of cells in mid and late S, and in some accumulation of cells in early S and G2/M phase at 24 and 48 h after treatment. In contrast, after hepatic artery infusion a significant increase of the fraction of cells in G2/M phase was observed at 24 h after treatment. Monitoring tumour growth after isolated liver perfusion five out of seven rats showed a complete tumour remission, while after hepatic artery infusion only a minimal growth delay was detected. This study demonstrates that isolated liver perfusion in the rat CC531 liver tumour model allows the administration of a well-tolerated dose of mitomycin C being high enough to induce a marked DNA synthesis inhibition and even complete tumour remission. PMID- 1906729 TI - Basal cell nuclear size in experimental oral mucosal carcinogenesis. AB - It has been suggested that the size of the nuclei of epithelial basal cells can be used in predicting the likelihood of malignant transformation of epithelium. This proposition was assessed in rat palatal epithelium after the carcinogen 4 nitroquinoline-1-oxide had been applied to the epithelium for varying periods of time. No consistent alterations in basal cell nuclear size, including area, perimeter, diameter and regularity of form were found with routine light microscopy as the epithelium passed through various stages of dysplasia to carcinoma. This finding casts doubt on the value of using a variation of basal cell nuclear size as a predictor of malignant transformation. PMID- 1906730 TI - DNA base composition of Rickettsia tsutsugamushi determined by reversed-phase high-performance liquid chromatography. AB - The DNA base composition of Rickettsia tsutsugamushi was determined by reversed phase high-performance liquid chromatography and compared with that of Rickettsia rickettsii. The G+C contents were 28.1 to 30.5 mol% for R. tsutsugamushi and 32.1 mol% for R. rickettsii. PMID- 1906731 TI - Genome sizes of mammalian and avian Ureaplasmas. AB - The sizes of the genomes of 12 Ureaplasma strains isolated from six mammalian and one avian species, as determined by pulsed-field gel electrophoresis, varied from 760 to 1,170 kilobase pairs (470 to 723 megadaltons); and these values encompassed the values for the genomes of Ureaplasma urealyticum strains. Variation of at least 54% in the genome sizes restricts the usefulness of this taxonomic criterion for the genus Ureaplasma. PMID- 1906732 TI - The type strain(s) of Listeria monocytogenes: a source of continuing difficulties. AB - The type strain of Listeria monocytogenes differs from wild-type L. monocytogenes strains in more characteristics than just the previously reported deficiency in hemolytic activity and virulence in the murine infection model. The type strain from the American Type Culture Collection (strain ATCC 15313) produces lecithinase, is hemolytic on rabbit (but not sheep) blood agar, lacks motility, and shows limited cytopathogenic effects on Caco-2 monolayers, whereas the type strain from the Special Listeria Culture Collection (strain SLCC 53) is unable to produce lecithinase, is nonhemolytic on rabbit or sheep blood agar, is motile, and shows no cytopathogenic effects on Caco-2 monolayers. PMID- 1906733 TI - Male endocrine functions in workers with moderate exposure to lead. AB - Evidence for the effect of occupational exposure to lead on the male endocrine system is conflicting. This study evaluated the primary (testicular) and secondary (hypothalamo pituitary testicular) effects of exposure to lead in 122 current lead workers and 49 non-exposed workers. The mean current blood lead concentration was 35.2 (range 9.6-77.4) micrograms/dl in the exposed workers, and 8.3 (range 2.6-14.8) micrograms/dl in the non-exposed workers. Concentrations of plasma luteinising hormone (LH) and follicle stimulating hormone (FSH) were both significantly higher in the exposed workers, but testosterone (T) was not significantly different between the two groups. In older exposed workers, however (greater than or equal to 40 years), plasma T concentrations were significantly lower, but LH and FSH concentrations were not significantly different. Compared with non-exposed workers, those exposed for less than 10 years had significantly raised LH and FSH and normal T concentrations whereas those exposed for 10 or more years had significantly lower T, and normal LH and FSH concentrations. The concentrations of LH and FSH showed a moderate increase in relation to blood lead concentrations in the range of 10 micrograms/dl to 40 micrograms/dl and thereafter reached a plateau or declined. No apparent trend for plasma T concentrations occurred. No significant difference in prolactin (PRL) concentration was noted. It is concluded that moderate exposure to lead was associated in dose related fashion with small but measurable changes in male endocrine functions that reflected both primary and secondary effects of lead on the testes and the hypothalamo pituitary testicular axis. PMID- 1906734 TI - Effect of nitrate tolerance and dipyridamole on the response to SIN1 in the human isolated saphenous vein. AB - The relaxant effects of nitroglycerin (NTG) and SIN1 on human vena saphena magna were studied in vitro. Nitrate tolerance was produced after incubation of the preparation with nitroglycerin (NTG 10 microM for 10 minutes). Vessels precontracted by serotonin (0.25 microM) and made tolerant to NTG exhibited a slight but significant shift (p less than 0.01) to the right of the dose-response curve to SIN1 (EC50 increased from 1.12 +/- 0.21 microM to 2.74 +/- 0.32 microM). The maximal relaxation was unaltered. On the contrary, there was a marked attenuation of the maximal relaxation to NTG in the nitrate-tolerant preparation (maximal relaxation decreased from 73 +/- 2% to 35 +/- 1%). Dipyridamole, a phosphodiesterase (PDe) inhibitor, significantly potentiated the responses to SIN1 on control rings (EC50 = 57.1 +/- 1.8 nM), and on NTG-tolerant rings it reversed the responsiveness to SIN1 (EC50 = 88.9 +/- 9.2 nM), which suggests that nitrate tolerance may be partially due to an increase in PDe activity. In conclusion we have demonstrated a slight cross-tolerance between SIN1 and NTG on human vena saphena magna. Nevertheless, after induction of in vitro NTG tolerance, the attenuation of responses to SIN1 is much less pronounced that the alteration of NTG relaxations. PMID- 1906735 TI - The effects of pretreatment with nitroglycerin on ischemic left ventricular dysfunction during coronary angioplasty. AB - To evaluate the degree to which nitroglycerin reduces myocardial ischemia and dysfunction induced by transient coronary occlusion, 19 patients were studied during coronary angioplasty of the left anterior descending coronary artery. After a control occlusion of 60 seconds, 0.2 mg nitroglycerin was administered intravenously and the occlusion was repeated for 60 seconds. Before and during the occlusion period, pulmonary capillary wedge pressure was measured, the intracoronary ECG was recorded, and ventricular volumes, ejection fraction, and regional systolic shortening were obtained by digital subtraction angiography. Nitroglycerin caused a significant fall in pulmonary capillary wedge pressure before (10 vs. 7 mmHg) and at 60 seconds occlusion (18 vs. 14 mmHg), but did not significantly delay the rise in wedge pressure (37 vs. 44 seconds). End-systolic left ventricular volume at 60 seconds of occlusion was reduced by nitroglycerin (77 vs. 68 ml), whereas regional shortening of the ischemic segments remained unchanged (22 vs. 23%). Nitroglycerin did not delay the onset of ischemic ST segment elevation (14 vs. 14 seconds) and had no effect on the changes of ST elevation in the intracoronary ECG (1.9 vs. 1.9 mV). These findings suggest that intravenous nitroglycerin reduces filling pressure and slightly improves left ventricular global function during acute coronary occlusion. Nitroglycerin, however, has little effect on ischemia-induced regional dysfunction and on ST segment elevation in the intracoronary ECG. PMID- 1906736 TI - Ischemia-reperfusion arrhythmias and lipids: effect of human high- and low density lipoproteins on reperfusion arrhythmias. AB - The effect of high- and low-density lipoproteins separated from human serum on the postischemic reperfusion arrhythmias was investigated. The hearts were perfused by working heart mode with Krebs Henseleit bicarbonate buffer containing arachidonic acid (1 microgram/ml) for 5 minutes. Whole heart ischemia was induced by the use of a one-way ball valve, and hearts were perfused for 15 minutes followed by 20 minutes of reperfusion. Physiologic concentrations of high- and low-density lipoproteins were constantly infused through the atrial route during ischemic perfusion. Coronary effluent was collected via pulmonary artery cannulation for subsequent radioimmunoassay of thromboxane B2 and 6-keto prostaglandin F1 alpha, the major stable metabolites of thromboxane A2 and prostacyclin, respectively. The incidence of ventricular arrhythmias during reperfusion was 6/6 (100%), 1/6 (17%), and 6/6 (100%) in control, high-density lipoprotein and low-density lipoprotein infusion groups, respectively. There was no significant difference in coronary flow among the three groups throughout the perfusion. Both thromboxane B2 and 6-keto-prostaglandin F1 alpha increased significantly during ischemia compared with preischemic values in all groups of hearts. However, the ratio of these two parameters varied in control and low density lipoprotein infusion groups during ischemia, while there was no significant change in the high-density lipoprotein infusion group. These results provide the possibility that arachidonate metabolites may be involved in the regulation of ischemia-reperfusion arrhythmias and that high-density lipoprotein that was infused during ischemia markedly inhibits the incidence of ischemia reperfusion-induced ventricular arrhythmias, due in part at least, to stabilizing the arachidonate metabolites during ischemic perfusion. PMID- 1906737 TI - The effects of several pharmacologic agents upon postischemic recovery. AB - Using an isolated working rat heart model, the effects of DL-verapamil, ryanodine, gabexate mesilate (FOY), recombinant human superoxide dismutase (RH SOD), and coenzyme Q10 upon myocardial protection were evaluated. Under conditions of normothermic ischemia, all these compounds, except RH-SOD, when added to the St. Thomas' cardioplegic solution at an optimal concentration, showed beneficial effects upon functional recovery and enzyme leakage. In contrast, the above compounds, except ryanodine and FOY, failed to improve the protective properties of the St. Thomas' cardioplegic solution under conditions of hypothermic ischemia. Our results indicate that calcium overload via the calcium channel and calcium-induced calcium release from sarcoplasmic reticulum (SR) may contribute to the onset of ischemic-reperfusion injury. However, under conditions of hypothermic ischemia, calcium-induced calcium release from SR plays a dominant role in calcium overload. Furthermore, intracellular calcium overload may activate proteases and result in the acceleration of myocardial injury. PMID- 1906738 TI - Analysis of sequences in domain II of Pseudomonas exotoxin A which mediate translocation. AB - Pseudomonas exotoxin (PE) contains 613 amino acids that are arranged into 3 structural domains. PE exerts its cell-killing effects in a series of steps initiated by binding to the cell surface and internalization into endocytic vesicles. The toxin is then cleaved within domain II near arginine-279, generating a C-terminal 37-kDa fragment that is translocated into the cytosol where it ADP-ribosylates elongation factor 2 and arrests protein synthesis. In this study, we have focused on the functions of PE which are encoded by domain II. We have used the chimeric toxin TGF alpha-PE40 to deliver the toxin's ADP ribosylating activity to the cell cytosol. Deletion analysis revealed that sequences from 253 to 345 were essential for toxicity but sequences from 346 to 364 were dispensable. Additional point mutants were constructed which identified amino acids 339 and 343 as important residues while amino acids 344 and 345 could be altered without loss of cytotoxic activity. Our data support the idea that domain II functions by first allowing PE to be processed to a 37-kDa fragment and then key sequences such as those identified in this study mediate the translocation of ADP-ribosylation activity to the cytosol. PMID- 1906739 TI - A fluorescence lifetime study of virginiamycin S using multifrequency phase fluorometry. AB - Using multifrequency phase fluorometry, fluorescence lifetimes have been assigned to the different protolytic forms of the antibiotic virginiamycin S. These lifetimes are 0.476 +/- 0.005 ns for the uncharged form, 1.28 +/- 0.2 and 7.4 +/- 0.2 ns for the zwitterionic form, 1.19 +/- 0.01 ns for the negatively charged form, and 1.9 +/- 0.1 ns for the double negatively charged form. The assignments are based on lifetime measurements as a function of pH, volume percent ethanol, and excitation wavelength. Excited-state proton transfer is taken into account. It is complete at pH values lower than 1, and no fluorescence of the fully protonated charged form is observed. At pH 8, an excited-state pK* increase is calculated, but proton association is too slow to cause excited-state proton transfer. The addition of divalent cations, at pH 9.4, increases the lifetime of the negatively charged form to a value dependent upon the specific nature of the cation (7.58 +/- 0.06 ns for Mg2+, 6.54 +/- 0.02 ns for Ca2+, and 3.74 +/- 0.05 ns for Ba2+). Monovalent cations do not influence the lifetimes, indicating that their binding to the macrocycle does not influence the fluorescent moiety. The model compound 3-hydroxypicolinamide shows an analogous behavior, but the retrieved lifetime can differ significantly. PMID- 1906740 TI - Interaction between virginiamycin S and ribosomes is partly provided by a salt bridge with a Mg2+ ion. AB - Type B streptogramins, such as virginiamycin S (VS), are cyclic hexadepsipeptides, inhibiting protein synthesis in prokaryotes. L-Thr connects a 3-hydroxypicolinyl residue (3-OH-Pic) to the peptide lactone ring. The fluorescence intensity of 3-OH-Pic is strongly increased by chelation to alkaline earth cations or binding to ribosomes. Similar behavior of the ribosome-VS complex and the VS-Mg chelate provides strong evidence for the presence of a VS Mg chelate within the ribosomal binding site. Different models involving the ribosome binding of either members of the VS-Mg2+ chelate or both have been tested by fluorescence lifetime measurements, equilibrium titrations, and stopped flow spectrofluorometry. Our data strongly suggest that (a) the interaction between VS and the ribosome is partly provided by a salt bridge between suitable acceptor atoms of the ribosome and the 3-OH-Pic residue, (b) Mg2+ can be exchanged by Mn2+ without dissociation of the ribosome-VS complex, (c) Mg2+ coordinates to the negative form of the 3-OH-Pic residue, probably via an interaction with the phenolate oxygen and the amide carboxyl group, and (d) the picolinyl residue is essential for the biological activity, as indicated by the lack of activity when the latter is replaced by a serine derivative. PMID- 1906741 TI - Two-dimensional magnetization exchange spectroscopy of Anabaena 7120 ferredoxin. Nuclear Overhauser effect and electron self-exchange cross peaks from amino acid residues surrounding the 2Fe-2S* cluster. AB - Hyperfine 1H NMR signals of the 2Fe-2S* vegetative ferredoxin from Anabaena 7120 have been studied by two-dimensional (2D) magnetization exchange spectroscopy. The rapid longitudinal relaxation rates of these signals required the use of very short nuclear Overhauser effect (NOE) mixing times (0.5-20 ms). The resulting pattern of NOE cross-relaxation peaks when combined with previous 1D NOE results [Dugad, L. B., La Mar, G. N., Banci, L., & Bertini, I. (1990) Biochemistry 29, 2263-2271] led to elucidation of the carbon-bound proton spin systems from each of the four cysteines ligated to the 2Fe-2S* cluster in the reduced ferredoxin. Additional NOE cross peaks were observed that provide information about other amino acid residues that interact with the iron-sulfur cluster. NOE cross peaks were assigned tentatively to Leu27, Arg42, and Ala43 on the basis of the X-ray coordinates of oxidized Anabaena 7120 ferredoxin [Rypniewski, W.R., Breiter, D.R., Benning, M.M., Wesenberg, G., Oh, B.-H., Markley, J.L., Rayment, I., & Holden, H. M. (1991) Biochemistry 30, 4126-4131]. Three chemical exchange cross peaks were detected in magnetization exchange spectra of half-reduced ferredoxin and assigned to the 1H alpha protons of Cys49 and Cys79 [both of whose sulfur atoms are ligated to Fe(III)] and Arg42 (whose amide nitrogen is hydrogen-bonded to one of the inorganic sulfurs of the 2Fe-2S* cluster). The chemical exchange cross peaks provide a means of extending assignments in the spectrum of reduced ferredoxin to assignments in the spectrum of the oxidized protein.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1906743 TI - Initiation of chondroitin sulfate biosynthesis: a kinetic analysis of UDP-D xylose: core protein beta-D-xylosyltransferase. AB - The nature of the primary signals important for the addition of xylose to serines on the core protein of the cartilage chondroitin sulfate proteoglycan has been investigated. The importance of consensus sequence elements (Acidic-Acidic-Xxx Ser-Gly-Xxx-Gly) in the natural acceptor was shown by the significant decrease in acceptor capability of peptide fragments derived by digestion of deglycosylated core protein with Staphylococcus aureus V8 protease, which cleaves within the consensus sequence, compared to the similar reactivity of trypsin-derived peptide fragments, in which consensus sequences remain intact. A comparison of the acceptor efficiencies (Vmax/Km) of synthetic peptides containing the proposed xylosylation consensus sequence and the natural acceptor (deglycosylated core protein) was then made by use of the in vitro xylosyltransferase assay. The two types of substrates were found to have nearly equivalent acceptor efficiencies and to be competitive inhibitors of each other's acceptor capability, with Km = Kiapparent. These results suggest that the artificial peptides containing the consensus sequence are analogues of individual substitution sites on the core protein and allowed the kinetic mechanism of the xylosyltransferase reaction to be investigated, with one of the artificial peptides as a model substrate. The most probable kinetic mechanism for the xylosyltransferase reaction was found to be an ordered single displacement with UDP-xylose as the leading substrate and the xylosylated peptide as the first product released. This represents the first reported formal kinetic mechanism for this glycosyltransferase and the only one reported for a nucleotide sugar:protein transferase. PMID- 1906742 TI - Heteronuclear 2D NMR studies of an engineered insulin monomer: assignment and characterization of the receptor-binding surface by selective 2H and 13C labeling with application to protein design. AB - Insulin provides an important model for the application of genetic engineering to rational protein design and has been well characterized in the crystal state. However, self-association of insulin in solution has precluded complementary 2D NMR study under physiological conditions. We demonstrate here that such limitations may be circumvented by the use of a monomeric analogue that contains three amino acid substitutions on the protein surface (HisB10----Asp, ProB28--- Lys, and LysB29----Pro); this analogue (designated DKP-insulin) retains native receptor-binding potency. Comparative 1H NMR studies of native human insulin and a series of three related analogues--(i) the singly substituted analogue [HisB10- --Asp], (ii) the doubly substituted analogue [ProB28----Lys; LysB29----Pro], and (iii) DKP-insulin--demonstrate progressive reduction in concentration-dependent line-broadening in accord with the results of analytical ultracentrifugation. Extensive nonlocal interactions are observed in the NOESY spectrum of DKP insulin, indicating that this analogue adopts a compact and stably folded structure as a monomer in overall accord with crystal models. Site-specific 2H and 13C isotopic labels are introduced by semisynthesis as probes for the structure and dynamics of the receptor-binding surface. These studies confirm and extend under physiological conditions the results of a previous 2D NMR analysis of native insulin in 20% acetic acid [Hua, Q. X., & Weiss, M. A. (1991) Biochemistry 30, 5505-5515]. Implications for the role of protein flexibility in receptor recognition are discussed with application to the design of novel insulin analogues. PMID- 1906744 TI - Linkage of thioredoxin stability to titration of ionizable groups with perturbed pKa. AB - The highly conserved, buried, Asp 26 in Escherichia coli thioredoxin has a pKa = 7.5, and its titration is associated with a sizable destabilization of the protein [Langsetmo, K., Fuchs, J., & Woodward, C. (1991) Biochemistry (preceding paper in this issue)]. A fit of the experimental pH dependence of thioredoxin stability to a theoretical expression for the pH/stability relation in proteins agrees closely with a pKa value of 7.5 for Asp 26. The agreement between the experimental and theoretical changes in protein stability due to substitution of Asp 26 by alanine is also good. The local structure in the vicinity of Asp 26 in the low-pH crystal structure (with uncharged Asp 26) is hydrophobic, indicating that the aspartate would be highly destabilized. In theoretical calculations, the desolvation penalty for deprotonating Asp 26 in this environment is similar to the total protein folding energy. As a consequence, the Asp 26 pKa would be much greater than 7.5, and/or the protein might not fold. This suggests that a compensating process partially stabilizes the Asp 26 carboxyl group when it is charged. A simple model for this proposed, whereby the Lys 57 side chain rotates to form a salt bridge with Asp 26 when it is deprotonated. PMID- 1906745 TI - Hemodynamic response to OKT3 in orthotopic heart transplant recipients: evidence for reversible myocardial dysfunction. AB - The murine-derived monoclonal antibody OKT3 has been shown to be a useful immunosuppressive agent in transplant recipients; but it may cause cardiac instability and hemodynamic findings similar to those seen in septic shock after a first dose. Eight patients who received orthotopic heart transplants and were randomized to OKT3 therapy for immunosuppression were evaluated with serial hemodynamic and radionuclide monitoring for an 8-hour period during the first dose of OKT3. Cytokines including tumor necrosis factor-alpha, interleukin-1 and 2, and interferon-gamma were measured hourly to determine the potential mechanism of action of OKT3. All patients tolerated OKT3, although most had symptoms- pyrexia, chills, dyspnea, nausea and vomiting, and fever--within an hour after the dose. All patients exhibited a biphasic hemodynamic response to the first dose of OKT3. The initial hemodynamic response was characterized by a hyperdynamic phase with involvement in cardiac function as measured by cardiac output and ejection fraction. Left ventricular ejection fraction increased from 68% +/- 10% to 79 +/- 11% and was accompanied by increases in right ventricular ejection fraction and increases in cardiac index from 2.1 +/- 1.1 to 3.8 +/- 1.3 L/min/m2. The increase in ejection fraction was accompanied by a significant decrease in systemic vascular resistance index, from 2190 +/- 740 to 1608 +/- 573 dyne.sec.cm-5. The improvement in left ventricular ejection was caused by a significant decrease in end-systolic volume index (18 +/- 9.5 to 11 +/- 7 ml/m2). This occurred within the first 2 hours after OKT3 and was followed by cardiac index and ejection fraction returning to baseline in the next 2 to 3 hours.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1906746 TI - Some aspects of changed histopathologic appearance of acute rejection in cardiac allografts after prophylactic application of OKT3. AB - The histopathologic findings of therapy-requiring acute rejection in the cardiac allograft observed in endomyocardial biopsy specimens taken from patients under prophylactic administration of OKT3 show certain differences in comparison with the classic description of acute rejection. These differences are characterized above all by a distinctly reduced cellularity of the infiltrates, with a relative decrease of T cells, as well as edema and retrogressive changes, up to necroses of myocytes with marked fragmentation; some patients also have increased vascular reactions. Furthermore, an earlier occurrence of and an increased frequency of changes corresponding to the so-called lymphoma-like lesions ("Quilty" effect) were observed in patients who received immunosuppressive prophylaxis with OKT3. The changed histopathologic findings of therapy-requiring acute rejection under prophylactic application of OKT3 may, to a certain extent, explain the discrepant results reported by different transplant groups with respect to the frequency of rejection episodes and the time when the first episode of therapy-requiring rejection occurs after heart transplantation. PMID- 1906747 TI - Effect of recombinant interferon gamma and interleukin-2 and of a monoclonal antibody against interferon gamma on the rat immune response against heart allografts. AB - We studied the effect of rat rec-IFN-gamma, human rec-IL-2, and an IgG1 monoclonal antibody (DB1) directed against rat IFN-gamma on allograft survival in the rat in various experimental conditions. The DB1 monoclonal antibody did not prolong heart allograft survival in the (LEW/BN)F1 to LEW combination, even when used at high doses (2 mg/rat x 9 days). Rec-IFN-gamma induced major histocompatibility antigen expression in vivo, but its administration had no effect on the graft survival either of untreated LEW recipients of (LEW x BN)F1 heart allografts or of donor blood-transfused LEW recipients. In addition, rec IFN-gamma alone had no effect on graft survival in cyclosporine-treated rats. In contrast, rec-IL-2 shortened heart allograft survival both in untreated and in cyclosporine-treated recipients. Rec-IFN-gamma partially reversed the effects of rec-IL-2 in cyclosporine-treated rats. The data suggest that in vivo administration of IFN-gamma in allograft recipients may have a suppressor effect, in addition to the postulated augmenting effect on the immune response by increasing MHC antigen expression. PMID- 1906748 TI - Cytochrome b5 and a recombinant protein containing the cytochrome b5 hydrophobic domain spontaneously associate with the plasma membranes of cells. AB - Both cytochrome b5, isolated from rabbit liver microsomes, and LacZ:HP, a recombinant protein consisting of enzymatically active Escherichia coli beta galactosidase coupled to the C-terminal membrane-anchoring hydrophobic domain of cytochrome b5, were shown to spontaneously associate with the plasma membranes of erythrocytes and 3T3 cells. Association was promoted by low pH values, but proceeded satisfactorily over several hours at physiological pH and temperature. About 150,000 cytochrome b5 molecules or 100,000 LacZ:HP molecules could be associated per erythrocyte. These proteins were not removed from the membrane by extensive washing, even at high ionic strength. After incubation with fluorescently labeled cytochrome b5 or LacZ:HP, cells displayed fluorescent membranes. The lateral mobility of fluorescently labeled cytochrome b5 and LacZ:HP was measured by photo-bleaching techniques. In the plasma membrane of erythrocytes and 3T3 cells, the apparent lateral diffusion coefficient D ranged from 1.0.10(-9) to 8.10(-9) cm2 s-1 with a mobile fraction M between 0.4 and 0.6. The lateral mobility of these proteins closely resembled that reported for lipid anchored proteins and was much higher than that reported for Band 3, an erythrocyte membrane-spanning protein with a large cytoplasmic domain. These results suggest that the hydrophobic domain of cytochrome b5 could be employed as a universal, laterally mobile membrane anchor to associate a variety of diagnostically and therapeutically useful recombinant proteins with cells. PMID- 1906749 TI - Active hexose transport across cultured human Caco-2 cells: characterisation and influence of culture conditions. AB - Human Caco-2 cells (passage 80 to 100) were seeded onto collagen-coated Millipore filter assemblies and these were maintained in culture either (a) floated on the surface of the medium or (b) submerged within the body of the medium. Structural and functional assessments were made over a 30-day period. After seeding, all cells assumed a flattened, squamous configuration and rapidly became confluent. Cells submerged within the medium formed polarised monolayers with well developed junctional complexes, abundant apical microvilli and increasing levels of alkaline phosphatase activity. Cells grown floated on the surface of the medium formed complex multilayers in which polarisation was confined to the surface layer. Junctional complexes and apical microvilli were similar to those seen in submerged monolayers but alkaline phosphatase activities were higher. Transepithelial electrical resistance increased rapidly from day 1, as the layers became confluent. Electrical resistance was higher and short-circuit current and potential differences were lower across monolayers than across multilayers. After 10 days in culture, the addition of D-glucose to the apical bathing solution, of all cell layers, caused a rapid rise in short-circuit current and potential difference. These changes were sodium-dependent and phlorizin-sensitive. Galactose and 3-O-methylglucose induced similar changes and the affinity constants for these hexoses ranked in the order reported for rat jejunum (Km glucose 2.44 +/- 0.52 mM; Km galactose 8.05 +/- 1.33 mM; Km 3-O-methylglucose 22.0 +/- 5.2 mM). Culture conditions had a marked effect on hexose maximum transport rates (glucose Vmax: submerged 2.94 +/- 0.20 microA/cm2; floated 9.94 +/- 0.82 microA/cm2, P less than 0.05) but affinity constants were unchanged. Apical to basolateral mannitol fluxes, used as an index of paracellular permeability, decreased from day 1 to day 5 and then remained steady. Fluxes across monolayers and multilayers were not significantly different. We conclude that sodium-dependent hexose transport occurs in cultured Caco-2 cell layers grown on permeable supports. Culture conditions, however, have a marked effect on both cell layer structure and function, and should be an important factor when considering Caco-2 cells as an in vitro model of enterocyte function. PMID- 1906750 TI - Prehemolytic effects of hydrogen peroxide and t-butylhydroperoxide on selected red cell properties. AB - To provide further understanding of how oxidative damage affects red cell membrane function, the effects of low levels of two different types of oxidants on selected red cell properties have been studied. Hydrogen peroxide (H2O2), an example of a water soluble oxidant, and t-butylhydroperoxide (tBHP), a hydrophobic hydroperoxide, were compared with respect to their effects on membrane permeability, membrane mechanical properties and binding of autologous serum antibodies to the cell surface. Whereas H2O2 treatment resulted in a dose dependent increase in membrane permeability to potassium that was evident after one hour of oxidant exposure, cells treated with tBHP at doses up to 5 mumol/ml cells showed no immediate change in cation permeability. H2O2 also caused a marked decrease in membrane deformability, whereas tBHP-treated cells showed minimal loss of deformability. However, tBHP treatment did result in a dose dependent increase in the susceptibility of the membrane to fragmentation under high shear stress. With exclusion of treated samples that bound excess rabbit anti-spectrin antibody, indicating exposure of intracellular components, neither agent promoted the binding of autologous serum antibody in amounts comparable to that found in vivo on high density or some pathologic red cells. Taken together, the results suggest that tBHP and H2O2 cause damage to human red cells by distinct oxidative mechanisms which do not lead directly to substantive generation of binding sites for autologous serum antibodies. PMID- 1906751 TI - Localization and activity of renal carbonic anhydrase (CA) in CA-II deficient mice. AB - A null allele at the mouse Car 2 locus was induced by ethylnitrosurea; mice homozygous for the new allele lack the carbonic anhydrase (CA)-II isoenzyme. The expression of this genetic lesion was investigated by: (1) using tissue fractionation techniques to determine localization and activity of CA in the kidney, and (2) examining renal response to CA inhibition in CA-II deficient mice (CAD), in normal (N) mice and in heterozygous litter mates (LM). N and LM mice had CA activity in proximal tubule brush border membranes and cytosol. CA activity was also localized to membranes and cytosol of the outer medullary region. CAD mice lacked cytosolic activity but had normal CA activity in all membranes examined. All membrane associated CA had 2-8-fold lower sulfonamide sensitivity than cytosolic CA. These inhibition characteristics suggest that the membrane enzyme is CA-IV. Baseline urinary excretion of Na+, K+, and HCO3- was similar in all groups. Urine pH and Cl- excretion were higher and titratable acid output was lower in CAD mice. Inhibition of CA (methazolamide, 25 mg/kg) led in all groups to equivalent increments of urine pH, urine flow, and HCO3-, Na+, and K+ excretion. Cl- excretion was unchanged. Thus the extent of the genetic deficiency of CA-II mice extends to the kidney cytosol but does not alter membrane localization or levels of CA, probably CA-IV. The similar response to CA inhibition in CAD mice suggests that CA-IV, the membrane bound isoenzyme is the important isoenzyme in proximal tubule HCO3- reabsorption. PMID- 1906752 TI - Aldosterone and chloride conductance of amphibian skin. AB - Chloride influx (JCl) across the skin of toads maintained in dilute MgCl2 or Na2SO4 was determined after overnight incubation with(out) aldosterone, and related to mitochondria-rich cell (MRC) density of the preparations. Adaptation to MgCl2 vs. Na2SO4 was reflected by higher plasma aldosterone in the former group (17 vs. 3 nmol/l, respectively) while JCl was lower, even after overnight incubation (172 vs. 318 pmol cm-2 s-1). Incubation with aldosterone induced a more pronounced increase in JCl in the case of Na2SO4- vs. MgCl2-adapted toads (delta JCl: 242 vs. 25 pmol cm-2 s-1, respectively), which could be related to difference in MRC density between these two groups (1078 vs. 615 cells/mm2, respectively). On the other hand, the in vitro effect of aldosterone on Na+ transport (assessed by Isc) was equally pronounced in both groups, and thus independent of MRC density. These data suggest that aldosterone, rather than being involved in MRC proliferation, stimulates Cl- conductance by influencing the functional state of MRC. PMID- 1906753 TI - [Septic arthritis caused by Streptococcus agalactiae in a patient with liver cirrhosis]. PMID- 1906754 TI - [Phenotypic characteristics of 100 strains belonging to the mesophilic aeromonas group isolated from feces]. AB - Phenotypic characteristics of 100 strains pertaining to the group of mesophilic aeromonas isolated in feces of patients with diarrhea (23 A. hydrophila, 34 A. sobria, 19 A. caviae, and 24 considered atypical because produced a the negative esculin reaction and a positive gas formation from glucose [TSI]). The percentages obtained in the different biochemical tests support the hypothesis that in this group there is a taxonomic complexity. We observed variations in the following tests: LDC, arabinose, Voges-Proskauser, lactose, and motility and hemolytic activity. We compared manual and automatic procedures in detecting esculinase and beta-galactosidase activity (ONPG). The study of constitutional enzymatic activity by means of API ZYM system can not be used to differentiate the distinct species although the enzyme beta-glucosidase is detected preferentially in A. hydrophila. PMID- 1906755 TI - Branhamella catarrhalis peritonitis in CAPD: an avoidable complication? PMID- 1906756 TI - Cytoskeletal origins in sulfur-metabolizing archaebacteria. AB - Several of the thermophilic acidopholic sulfur-metabolizing archaebacteria lack rigid cell walls. Their irregular shapes were maintained by an internal mechanism, presumably a cytoskeleton. Apparently this is an adaptation for respiration upon elemental sulfur, which requires cell contact since sulfur is insoluble in water. Also, we speculate that there could be additional functions of the cytoskeleton, such as prevention of osmotic cell lysis, thermal stabilization of enzymes, and improvements in metabolic efficiency through specific enzyme positioning. Such a well-developed cytoskeleton, evolving first in thermophilic archaebacteria, could have been a preadaptation for the evolution of eukaryotic cells. PMID- 1906757 TI - On the evolution of the karyorelict ciliate life cycle: heterophasic ciliates and the origin of ciliate binary fission. AB - Karyorelict ciliates have near diploid somatic nuclei (macronuclei) incapable of division. If selective pressure favors nuclear division, how could such macronuclei have evolved? I propose that they initially evolved in the context of a diplophase stage that consisted entirely of a non-dividing trophont that was terminated by the induction of meiosis. The diploid macronucleus then differentiated, functioned and was destroyed in the absence of cell division. Such a life cycle would necessarily be heterophasic, i.e. with alternating haploid and diploid generations. I call these ancestors heterophasic ciliates. I further propose that the ability of this diploid trophont to undergo binary fission arose de novo. Ciliate binary fission would then be a derived characteristic, which possibly evolved indepedently in more than one heterophasic ciliate lineage. A progression of steps, leading to the reduction of the haplophase and the generation of the karyorelict life cycle, is proposed. The shared possession of nuclear dimorphism with non-dividing macronuclei, conjugation, and a putative heterophasic ancestry invites further investigation of the phylogenetic relationship between heterokaryotic foraminifera and karyorelict ciliates. PMID- 1906758 TI - [The NMR tomographic findings in von Recklinghausen's disease with extensive neurofibromas]. PMID- 1906759 TI - [The anti-ischemic action of a perfluorocarbon emulsion (PFCE) on the canine myocardium]. AB - On the 60th minute after inducing the acute ischemia in the canine myocardium by the occlusion of the left anterior descending coronary artery, the animals were intravenously infused with perfluorochemical emulsion (PFCE), its salt composition (SC) or 4% surface-active substance (SAS), proxanol, at a dose of 10 ml/kg. Two hours after infusion, the occlusion was removed (reperfusion). The arterial pO2 was maintained at 120 mm Hg. Analysis of the blood flow, oxygen supply, acid-alkali balance, ECG, as well as creatine phosphokinase activity, measured in the ischemic area, has shown that PFC emulsion is capable of reducing ischemic damage and preventing reperfusion-induced myocardium injury. Thus, the presence of perfluorochemicals in the PFC emulsion is an essential factor in its ischemia-protective effect. PMID- 1906760 TI - [The lymphocyte acetylcholinesterase activity in rats poisoned by pesticides]. AB - The experiments carried out present the evidence of acetylcholinesterase activity of Wistar rat lymphocytes. It was shown that splenocytes and thymocytes had significantly different levels of the enzyme activity. Peroral administration of phosphor-organic pesticide antio (phormothion) 1/100 and 1/20 LD50 induced the dose-dependent inhibition of splenocyte acetylcholine-esterase activity after 2 months of treatment. It suggests the relation of the immunosuppressive action of pesticide with the interference into the neuromediator mechanisms regulating the lymphoid cell function. PMID- 1906761 TI - [Polymer-metal complexes of the Mycobacterium protein antigen prevent the dissemination of postvaccinal infection in the T-deficiency state]. AB - Primary obtained triple highly immunogenetic complex consists of nonimmunogenic protein antigen, isolated from the BCG, nontoxic polyelectrolyte and bivalent cuprum ions. Immunization with this complex provides high immunoprotection in the experimented B mice (T-deficit mice) from lethal dissemination BCG. Inoculation of single components of the complex has no protection. Result of these experiments suggest that antigen-polyelectrolyte complexes obtained on the basis of nonimmunogenic protein fraction of the tuberculosis bacilli show the properties of a thymus-independent immunization preparations, and provide immune defense in the T-cell deficit of the immune system. PMID- 1906762 TI - Disinfection of endoscopic equipment. AB - Patients undergoing endoscopy are at risk of infection from the use of contaminated equipment. Dangers arise from the transmission of organisms from one patient to another and from the introduction of opportunist organisms which colonize endoscopic equipment on storage and can lead to sepsis and death in those who are immunocompromised and at ERCP. Staff are in danger from needle stick injury and sensitivity to aldehyde disinfectants. These risks can be eliminated by careful attention to disinfection techniques. The most important part of endoscope disinfection is thorough mechanical cleaning first, followed by 5-10 min total immersion of the instrument and all channels in 2% glutaraldehyde (or the equivalent). At the end of the endoscopy list, following the disinfection protocol, all equipment should be dried internally and externally prior to storage. Staff must be fully aware of the risks of infection in endoscopy, be protected from hepatitis B by vaccination, and be fully trained in disinfection techniques. Glutaraldehyde should be used only in closed systems or in well ventilated areas with the operator protected from direct contact from splashing and fumes. Institutions should designate an individual to be responsible for preparing, monitoring and overseeing disinfection procedures within the endoscopy room and for ensuring that regular microbiological testing of equipment (including automatic disinfecting machines) is undertaken. PMID- 1906764 TI - Alzheimer's disease and the beta amyloid gene. PMID- 1906763 TI - Iron-mediated induction of the SOS responses by hydrogen peroxide. PMID- 1906765 TI - Body concentration of caesium-137 in patients from Western Isles of Scotland. AB - OBJECTIVES: To compare caesium-137 concentrations in patients from the Western Isles Health Board, Glasgow area, and other parts of the Scottish mainland, and to investigate the source of 137Cs in patients from the Western Isles. DESIGN: Study of hypertensive patients having electrolyte concentrations measured, including 137Cs. Interview by questionnaire of island subjects about intake of foods likely to contain radiocaesium and the source of these foods. Measurement of 137Cs and 134Cs in food, urine, and vegetation. SETTING: Scottish mainland and Western Isles, 1979-86. All measurements before Chernobyl nuclear accident. PATIENTS: 413 consecutive patients referred to the blood pressure unit for investigation of hypertension. 60 from the Western Isles, including 44 from North Uist; 32 from North Uist participated in the dietary analysis. MAIN OUTCOME MEASURES: Concentration of radiocaesium in the body, urine, food, and vegetation. Islanders' consumption of local produce. RESULTS: Patients from the Western Isles had five times higher body concentrations of 137Cs (median 2.54 (interquartile range 1.25-3.73)) Bq/gK) than did patients from around Glasgow (0.47 (0.26-0.66) Bq/gK) and other parts of the Scottish mainland (0.42 (0.24-0.71) Bq/gK). Islanders often consumed local milk and mutton, but ate local fish rarely. 137Cs and 134Cs were present in coastal (21.6 Bq/kg 137Cs, 0.25 Bq/kg 134Cs) and moorland (135.9, 0.65 Bq/kg) grasses and in islanders' urine (2.01, 0.013 Bq/l). Lower concentrations (0.336, 0.004 Bq/l), were found in the urine of Glasgow controls (p less than 0.001 for both isotopes). CONCLUSIONS: Islanders have excess body 137Cs concentrations, most of which probably comes from local milk and lamb. The radioactivity is not above the recommended safety limit. The presence of 134Cs suggests that nuclear reprocessing is the source of some of the radiocaesium. PMID- 1906766 TI - Cost effectiveness of cardiac defibrillation by general practitioners. PMID- 1906767 TI - Pinacidil inhibits the ryanodine-sensitive outward current and glibenclamide antagonizes its action in cells from the rabbit portal vein. AB - Pinacidil, a potassium-channel opener, inhibited the ryanodine-sensitive oscillatory outward potassium current induced by Ca released from an intracellular store. Glibenclamide, a blocker of the ATP-sensitive K-channel, prevented the action of pinacidil, suggesting the presence of an additional site (to K channels) for the vasodilator actions of pinacidil at which glibenclamide can act as an antagonist. PMID- 1906768 TI - Human vascular smooth muscle cells inhibit platelet aggregation when incubated with glyceryl trinitrate: evidence for generation of nitric oxide. AB - 1. The effect on platelet aggregation of glyceryl trinitrate in the presence of cultured vascular smooth muscle cells was determined turbidometrically. U46619 (a thromboxane mimetic) was used as agonist and experiments were performed in the presence of aspirin. Inorganic nitrite production from glyceryl trinitrate by vascular smooth muscle cells was also measured, to provide an indirect index of nitric oxide synthesis. 2. The combination of vascular smooth muscle cells together with glyceryl trinitrate, at concentrations that had little effect individually, profoundly inhibited platelet aggregation. 3. The inhibitory effect on platelet aggregation of vascular smooth muscle cells together with glyceryl trinitrate was markedly attenuated by haemoglobin, an inhibitor of nitric oxide. 4. These results show that vascular smooth muscle cells inhibit platelet aggregation when exposed to glycerol trinitrate and suggest that this is due to generation of nitric oxide from glyceryl trinitrate by vascular smooth muscle. PMID- 1906769 TI - Effects of early experience on c-fos gene expression in the chick forebrain. AB - The expression of c-fos mRNA was studied by blot and in situ hybridisation in the forebrains of young chicks subjected to different types of experience-dependent stimulation. Exposure to one hour of activity in a rich visual environment produced a significant increase in forebrain c-fos mRNA in 1-day or 2-day-old chicks; this increase was most marked in cerebellum and medial forebrain- especially intermediate medial hyperstriatum ventrale (IMHV) regions. Levels of c fos mRNA were not elevated in birds which had been accommodated to the enriched environment for 2 days, suggesting that the novelty of presented stimuli play a critical role in the c-fos induction. Training chicks on a one-trial passive avoidance task was followed by 2- to 2.5-fold increases in c-fos mRNA in both left and right IMHV and lobus parolfactorius (LPO) 30 min after the learning experience. Occlusion of one eye during training resulted in an asymmetrical expression of c-fos in the hemisphere contralateral to the open eye. Therefore c fos is induced in the chick forebrain during learning and its activation cannot be attributed to 'stress', arousal or intensity of sensory stimulation alone. These observations support the hypothesis that c-fos expression in the brain is related to the acquisition of new experience. PMID- 1906770 TI - Synaptogenesis in the rat suprachiasmatic nucleus: a light microscopic immunocytochemical survey. AB - MabQ155, a monoclonal antibody against synaptophysin, has been used to conduct a light microscopic survey of synaptogenesis in the suprachiasmatic nucleus of the perinatal rat. Synaptophysin is an integral component of synaptic vesicle membranes which is expressed in growth cones and growth cone filopodia as well as in mature synapses. With the light microscope, mabQ155 immunoreactivity in growth cones can be distinguished from that in presynaptic terminals on the basis of the size of immunoreactive puncta. The current study presents a qualitative and quantitative analysis of synaptogenesis from the day of birth (P0) to postnatal day 10 (P10). In our quantitative analysis we have used daily intervals during the first postnatal week, distinguished between growth cones and presynaptic terminals, and divided the suprachiasmatic nucleus into sampling regions that are related to the progress of synaptogenesis. Our data demonstrate regional differences in synaptogenesis within the suprachiasmatic nucleus (SCN), document the temporal progression from the penetration of growth cones to the appearance of mature synapses, and provide information about gradients of synaptogenesis in the nucleus during development. PMID- 1906771 TI - The crayfish neuronal cytoskeleton: an investigation of proteins having neurofilament-like immunoreactivity. AB - We have evaluated the possibility that proteins similar to mammalian neurofilament proteins (NFPs) are present in crustacean neurons. A panel of monoclonal antibodies (mAbs), raised against mammalian NFP, was used to identify candidate proteins. The degree to which these proteins are similar to mammalian NFPs was further evaluated using the following criteria: tissue specificity, recognition by the neurofilament-specific Bodian silver strain, recognition by the intermediate filament-specific Pruss mAb, and insolubility following detergent-extraction. Three candidate polypeptides were identified by mAb screening: a very high molecular weight polypeptide (Mr greater than 300 kDa), a 40 kDa polypeptide, and a group of 4 bands at Mr = 66-84 kDa. Although all of these polypeptides were recognized by one or more anti-NFP mAb, not one of them was found exclusively in neuronal tissue, not one was stained by the NFP-specific Bodian method, and all were soluble under conditions in which mammalian NFPs are insoluble. As a result of this thorough evaluation, we conclude that crayfish neurons do not contain neurofilament-like proteins. Although not closely related to mammalian neurofilaments, the very high molecular weight crayfish polypeptide which was strongly labeled by a commercially available anti-NF-M mAb (clone NN18) during the mAb screening, may be a novel cytoskeletal protein. The evidence for this conclusion comes from immunocytochemical labeling experiments. Indirect immunofluorescence labeling of this protein differentially labeled axons, such that labeling intensity of specific axons was proportional to the relative concentration of cytoskeletal organelles in those axons. Labeling of neuronal cell bodies delineated a fibrous network throughout the cytoplasm, and intensely labeled microtubule-rich regions of cytoplasm which are characteristic of larger neuronal somata. Immunogold labeling and electron microscopic analysis of the distribution of this protein revealed that the NN18-clone antibody bound to an antigen located on microtubule side-arms. PMID- 1906772 TI - Nutritional problems of the elderly. AB - Malnutrition is common in elderly persons living in institutions and in the community. In many cases, the problem arises from a highly individual constellation of interacting physiologic, economic, and psychosocial causes that have the common effect of reducing nutrient intake. Protein-calorie and micronutrient undernutrition added to the normal effects of aging can undermine functional independence and diminish the quality of life of the elderly. The spectrum of the elderly is extremely broad, and, consequently, nutritional assessment and support must be highly individualized to be effective. A multidisciplinary approach focusing on prompt identification and treatment of correctable causes of undernutrition is most effective. There is a wide range of support modalities, from simple supplemental foods to total parenteral nutrition, any of which may be used successfully in an elderly patient, provided that the necessary care is taken to define the goals of therapy and to provide patient assessment and monitoring. PMID- 1906773 TI - Predominant expression of lambda light chain in adult cases with non-T-cell acute lymphocytic and chronic myelogenous leukemia in lymphoid blast crisis. AB - The authors investigated cytoplasmic immunoglobulins of the leukemic cells from 20 adult cases with non-T-cell acute lymphocytic leukemia (ALL) and from three cases with chronic myelogenous leukemia in lymphoid blast crisis using immunoelectron microscopy. They also studied these cases using various monoclonal antibodies. Of the 23 examined cases, nine were negative for both heavy and light chains of immunoglobulins; the authors defined these as common ALL. Two cases were positive for the mu chain but were negative for light chains; the authors defined these as pre-B-cell ALL. The remaining 12 cases were positive for either kappa or lambda light chains; these were defined as B-cell ALL. Of the 12 cases positive for light chains, 11 were positive for the lambda chain. Seven cases of the 11 positive cases for the lambda chain were negative for heavy chains. Eleven cases were positive either for both My4 and My9 or for one of the two antibodies. From these results, the authors conclude the following: (1) the ratio of pre-B cell ALL among non-T-cell ALL cases (two of 23 cases) was lower in adults than in children; (2) of the light chain-positive cases, the lambda light chain-positive cases predominated (11 of 12 cases); (3) heavy chain-negative, lambda chain positive cases (seven cases) were observed; and (4) one half of the leukemia cases showed dual phenotypes of B-cell and myeloid cell lineages. PMID- 1906774 TI - Diffuse large cell lymphoma occurring in a patient with Waldenstrom's macroglobulinemia. Evidence for the two different clones in Richter's syndrome. AB - The authors report a 60-year-old man with Richter's syndrome, or diffuse large cell lymphoma (DLCL) occurring in a patient with either chronic lymphocytic leukemia (CLL) or Waldenstrom's macroglobulinemia (WM). Surface marker analysis revealed that the WM showed mu kappa surface immunoglobulin (Ig) chains, and that the DLCL showed mu lambda Ig chains. Flow cytometric DNA analysis demonstrated DNA content differences between WM and DLCL, the former diploid and the latter aneuploid. The current study suggests that Richter's syndrome derives from two independent B-cell malignancies. PMID- 1906775 TI - Pathologic changes associated with androgen deprivation therapy for prostate cancer. AB - Prostate glands exposed to androgen deprivation with leuprolide +/- flutamide were evaluated for pathologic changes which might be related to therapy. Comparing pretreatment and posttreatment tissue by visual discrimination using light microscopic study revealed treatment-related alterations in the size and distribution of neoplastic glands in 60% of cases. Quantitative measurements documented glandular changes in an even greater percentage of cases. Although distinctive, the histologic pattern was not specific for leuprolide/flutamide. The absence of appreciable degeneration and necrosis in tumor cells suggests that this type of androgen deprivation may act through suppression rather than ablation of prostatic cancers. The relationship between treatment-related histologic effects and initial tumor grade and clinical stage as well as expression of prostate-specific antigen was studied. Accurate histologic assessment of leuprolide/flutamide-treated prostate glands should not be a problem so long as specimens are thoroughly examined and drug-related variations in tumor morphologic features are appreciated. PMID- 1906776 TI - Serum poly(A)polymerase levels in rats during induction of mammary carcinoma with 7,12-dimethylbenz[a]anthracene. AB - Levels of activity of poly(A)polymerase (polynucleotide adenylyl transferase), the enzyme responsible for the addition of poly(A) tracts to the 3'-termini of eukaryotic mRNAs were assayed in the serum of rats during induction of mammary carcinoma by intragastric administration of 7,12-dimethylbenz[a]anthracene (DMBA, 10 mg/rat). An appreciable rise in the levels of poly(A)polymerase coincided with the growth of palpable DMBA-induced mammary carcinoma, which then dropped sharply 2 weeks later when the tumor incidence reached its peak of 65%. PMID- 1906777 TI - Malignant mesothelioma: the antiproliferative effect of cytokine combinations on three human mesothelioma cell lines. AB - Tumour necrosis factor (TNF) combined with gamma-interferon (IFN gamma) is known to have antiproliferative effects on many tumour cells, both in vitro and in vivo. We investigated whether human mesothelioma cells would respond in a similar way. Mesothelioma cell lines established from primary tumours did not respond significantly in vitro to either TNF or IFN gamma alone but were inhibited by combinations of TNF and IFN gamma at concentrations as low as 5 ng/ml. In contrast, a mesothelioma cell line established from a metastatic tumour was sensitive to IFN gamma both alone and in combination with TNF but not to TNF alone. We also looked at the responses of one primary tumour cell line and the metastatic tumour cell line to alpha-interferon (IFN alpha) both alone and in combination with TNF. Both cell lines were sensitive to IFN alpha but were more sensitive to the THF/IFN alpha combination. We conclude that these low dose combinations of cytokines are worth further investigation in the development of mesothelioma therapy. PMID- 1906778 TI - Pharmacodynamics of mitomycin C in cultured human bladder tumors. AB - The effects of mitomycin C (MMC) concentration and exposure time on the inhibition of tumor cell labeling index (LI) were studied using surgical bladder tumor samples from 14 patients. The bladder tumors were cultured as 1-mm3 fragments on collagen gels. LI was determined by incorporation of [3H]thymidine and autoradiography. All tumors responded to MMC. However, the sensitivity varied significantly between tumors. At a 2-h exposure, the concentrations required for 50 and 90% inhibition (IC50 and IC90) ranged from 0.237 to 14.9 and 2.76 to 74.5 micrograms/ml, respectively. There was an inverse correlation between MMC activity and tumor LI; the IC values were higher for the more rapidly proliferating tumors. Exposure time had a pronounced effect on MMC activity. Shortening the exposure time from 2 to 0.5 h increased the IC50 3-fold, while prolonging the exposure time from 2 to 24 h decreased the IC50 6-fold. To determine the minimum concentration and exposure time necessary to reduce tumor LI by 90%, the data for 6 tumors were computer fitted to the pharmacodynamic relationship Cn x T = k. The analysis showed that, on average, a 2.5-h exposure of 3 micrograms/ml was needed for 50% inhibition and a 7-h exposure of 8 micrograms/ml was needed for 90% inhibition. A comparison of the IC values of MMC determined in this study with the literature values determined using monolayer and spheroid cultures of established human bladder tumor cell lines showed that the drug activity in cultured tumor fragments ranged from 7- to 5300-fold lower than that in established cell lines. In summary, our data demonstrate a heterogeneity in the response of bladder tumors from individual patients to MMC, a decreased sensitivity to MMC with increasing tumor proliferation, and that drug concentration and exposure time are critical determinants of MMC activity. PMID- 1906780 TI - Enhancement of metastatic potential by gamma-interferon. AB - Preincubation of murine colon 26 colon adenocarcinoma cells with gamma-interferon (IFN-gamma), but not alpha-interferon, produced a significant increase in experimental pulmonary metastases in syngeneic BALB/c and T-cell-deficient BALB/c nude mice. The enhancement was seen after as little as 1 h of exposure to 1 unit/ml of IFN-gamma and persisted for at least 72 h following removal of the cytokine. IFN-gamma exerted its effects by increasing the pulmonary retention of cells during the first 6 h following tumor cell injection. During this period all cells visualized in the lung were trapped in pulmonary capillaries. The enhancement was not due to modulations in class I major histocompatibility complex surface antigen expression; nor was it due to alterations in cell size, adhesion to components of the extracellular matrix in vitro, heterotypic or homotypic adhesion, sensitivity to lysis by activated peritoneal macrophages, osmotic fragility, enhancement of surface class II major histocompatibility complex antigen expression, or enhancement of intercellular adhesion molecule-1 (ICAM-1). Colon 26 was completely resistant to natural killer cell-mediated lysis in vitro, and IFN-gamma did not modulate the ability of colon 26 to form conjugates with isolated splenocytes. In vivo elimination of anti-asialo GM1 + cells increased pulmonary metastasis, and in such mice, there was no longer a difference in metastatic potential between control and IFN-gamma-treated cells. We conclude that low doses of IFN-gamma generated at the site of the tumor by host-infiltrating cells or during cytokine therapy could enhance the survival of tumor cells in the circulation and enhance their metastatic potential. PMID- 1906779 TI - Phase I evaluation of combination therapy with interleukin 2 and gamma interferon. AB - Recombinant interleukin 2 (IL-2) is a potent inducer of lymphokine-activated killer (LAK) activity directed against autologous and allogeneic tumors; these effects are mediated by CD3-negative, CD56-positive, and CD16-positive lymphocytes. Although IL-2 therapy has been associated with clinical responses, particularly in patients with renal cell carcinoma and melanoma, these responses have occurred with high, toxic doses of this cytokine. Since gamma-interferon (IFN-gamma) potentiates LAK activity in vitro and in animal models, we initiated a dose-escalating Phase I trial of IFN-gamma and IL-2 in patients with advanced cancer. Patients were treated three times weekly (Monday, Wednesday, and Friday) for 6 weeks with bolus injections of IL-2; each dose was preceded 2 h earlier by a s.c. injection of IFN-gamma. Patients were treated with IFN-gamma at 0.01, 0.05, 0.1, or 0.25 mg/m2/dose. At each IFN-gamma dose, cohorts of at least three patients were treated with IL-2 at 1, 2.5, 5.0, or 7.5 x 10(6) Cetus units/m2 dose. Patients with clinical responses continued therapy three times weekly, while those with stable disease at 6 weeks were then treated twice weekly. A total of 41 patients were treated, all with Eastern Cooperative Oncology Group performance status 0 or 1. All patients were evaluable for toxicity. Dose limiting toxicities were cumulative fatigue and constitutional symptoms. One documented transmural myocardial infarct occurred. The maximally tolerated dose combination, based on analysis of IL-2 dose intensity, was 0.1 mg IFN-gamma/m2 and 7.5 x 10(6) Cetus units IL-2/m2 per dose. Two partial responses and two minor responses were observed. Treatment was not associated with dose-associated changes in peripheral blood lymphocyte phenotype, but there was a trend favoring IFN-gamma dose-associated rises in IL-2 induction of natural killer and LAK activity by treated patients' lymphocytes. Analysis of the cumulative effects of therapy on induction of natural killer and LAK activity by measurement of the median area under the curve of activation showed clear evidence of IFN-gamma and IL-2 dose-associated changes. The IL-2 dose effects on cell lysis were monotone, while the optimal IFN-gamma dose appeared to be 0.1 mg/m2/dose, with a bell shaped dose-response curve described previously for other effects of this cytokine. Using this novel statistical method of evaluating the biological effects of treatment, the optimal biological dose was identical to the maximally tolerated dose.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1906781 TI - Effect of glibenclamide on extracellular potassium accumulation and the electrophysiological changes during myocardial ischaemia in the arterially perfused interventricular septum of rabbit. AB - STUDY OBJECTIVE: The aim was to study the effects of glibenclamide on the rate of rise of extracellular potassium concentration ([K+]o) and the electrophysiological changes that occur during myocardial ischaemia. DESIGN: The study was performed in isolated, arterially perfused interventricular septa from the rabbit. Six septa were treated with glibenclamide 10(-6) mol.litre-1 and there were six untreated controls (vehicle only). [K+]o and electrophysiological variables were compared before and during a 30 min period of global zero flow ischaemia. MEASUREMENTS AND MAIN RESULTS: Prior to ischaemia, the extracellular potassium concentrations measured using potassium sensitive valinomycin electrodes were similar in the control and glibenclamide groups being 4.0 (SEM 0.1) and 4.0 (0.1) mmol.litre-1 respectively. [K+]o rose during ischaemia in both groups, and at 30 min was 13.3 (0.7) mmol.litre-1 in the control group. The increase in the glibenclamide group was less marked, reaching 9.2 (0.5) mmol.litre-1 (p less than 0.0005; unpaired t test). Glibenclamide had no electrophysiological effects prior to ischaemia. However, during ischaemia the decrease in action potential amplitude, action potential duration (APD), maximum upstroke velocity of the action potentials (dV/dtmax), and the extent of resting membrane potential (Em) depolarisation were less in the glibenclamide group than in the controls. The effective refractory period (ERP) progressively shortened over the 30 min of ischaemia in both groups, to a similar extent. When taken in conjunction with the relative changes in action potential duration the degree of post-repolarisation refractoriness (ERP-APD) that developed was less in the glibenclamide group than in the controls. CONCLUSIONS: Glibenclamide attenuated the ischaemic rise in [K+]o, with preservation of both membrane potential and action potential amplitude, duration, and upstroke velocity together with less post-repolarisation refractoriness. These effects could be potentially antiarrhythmic in acute myocardial ischaemia. PMID- 1906782 TI - Inhibition by barium and glibenclamide of the net loss of 86Rb+ from rabbit myocardium during hypoxia. AB - STUDY OBJECTIVE: The aim was to determine the effects of barium ions and glibenclamide on the hypoxia induced K+ efflux from rabbit myocardium. DESIGN: Experiments were performed on the isolated interventricular septum of the rabbit perfused with a physiological solution through the septal artery. The stimulation rate was 90 beats.min-1 and the temperature 32 degrees C. The flux of 86Rb+ was used as a surrogate of K+ fluxes. EXPERIMENTAL MATERIAL: Septa were obtained from adult male New Zealand white rabbits. MEASUREMENTS AND MAIN RESULTS: The uptake of 86Rb+ by the septum could be fitted to a single exponential curve with a rate constant of 0.024(SEM 0.001) min-1 (n = 14). Washout experiments were performed in which septa were labelled with 86Rb+ and then perfused with unlabelled solution for 60 min. The rate constants for the efflux of 86Rb+ were similar and were 0.022(0.001) min-1 (n = 13) for radioactivity in the tissue and 0.029(0.001) min-1 (n = 13) for radioactivity in the effluent. These rate constants were similar to those reported previously for 42K+. Septa were labelled for 150 to 180 min with 86Rb+ and then perfused with a hypoxic substrate free solution for 15 min followed by reoxygenation. The net loss of 86Rb+ was calculated to be equivalent to 4.00(0.20) mmol.kg-1 wet tissue of K+ (n = 8) and in washout experiments (n = 6) this loss was shown to be due to increased efflux. Ba2+, 0.1 mM and 1.0 mM, added at the onset of hypoxia decreased net tissue loss of 86Rb+ by 64(6)% (n = 5) and 97(1)% (n = 6) respectively (both p less than 0.01). Glibenclamide (0.1 mM) decreased tissue net loss by 52(3)% (n = 6, p less than 0.01). CONCLUSIONS: Part of hypoxia induced net K+ loss in this preparation can be attributed to activation of ATP sensitive K+ channels but other mechanisms are also involved. PMID- 1906783 TI - Determination of Fura-2 dissociation constants following adjustment of the apparent Ca-EGTA association constant for temperature and ionic strength. AB - The accurate calibration of Fura-2 fluorescence in living cells is dependent upon the apparent dissociation constant (Kd) of Fura-2 for Ca2+. If Ca-EGTA calibration buffers are used to construct an in vitro calibration curve, then the calculated value of the apparent Ca-EGTA association constant (K'CaEGTA) will have an important influence on the Kd of Fura-2 and thus the calculated free [Ca2+] in cells. In order to simulate experimental conditions, the individual proton and Ca2+ association constants for EGTA in these experiments were adjusted for both ionic strength and temperature using a semi-empirical form of the Debye Huckel limiting law and the Van't Hoff isochore, respectively, as described by Harrison and Bers. The modified individual binding constants were then employed in the calculation of K'CaEGTA using the SPECS computer program of Fabatio. At pH = 7.05, ionic strength = 0.15 M, temp = 20 degrees C, K'CaEGTA = 3.232 x 10(6) M 1; at pH = 6.84, temp = 36 degrees C, K'CaEGTA = 1.652 x 10(6) M-1. These values differed substantially from those obtained with unadjusted individual association constants. Calibration buffers of varying [Ca2+] were prepared using the corrected values of K'CaEGTA, and Fura-2 fluorescence ratios were measured during superfusion of these buffers in the experimental chamber at both 20 degrees C and 37 degrees C. The Kd of Fura-2 for Ca2+ was determined to be 236 nM at 20 degrees C and 285 nM at 37 degrees C, utilizing the value of K'CaEGTA adjusted by the method of Harrison and Bers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1906784 TI - Ammonium ions mobilize calcium from an internal pool which is insensitive to TRH and ionomycin in bovine anterior pituitary cells. AB - The effects of NH4Cl on cytoplasmic free calcium concentration ([Ca2+]i) and pH (pHi) in single bovine anterior pituitary cells were determined using fluorescence imaging microscopy. Addition of NH4Cl (10-40 mM) in the presence of 1 mM extracellular calcium ([Ca2+]e) increased [Ca2+]i to a peak which then fell to a sustained plateau, returning to resting levels upon removal of NH4Cl. In medium containing 0.1 microM [Ca2+]e, or in 1 mM [Ca2+]e medium containing 0.1 microM nitrendipine, the plateau was absent leaving only a transient [Ca2+]i spike. NH4Cl also increased pHi and this, like the [Ca2+]i plateau, remained elevated during the continued presence of NH4Cl. In medium containing only 0.1 microM [Ca2+]e, to preclude refilling of internal stores by entry of external calcium, repeated exposures to NH4Cl induced repeated [Ca2+]i transients. In contrast, only the initial exposure to thyrotropin releasing hormone (TRH; 20-500 nM) caused a [Ca2+]i rise but, after an additional exposure to NH4CI, TRH responses re-emerged in some cells. Pre-treatment with the calcium ionophore ionomycin abolished the rise caused by TRH, but neither TRH nor ionomycin pretreatment affected the response to NH4Cl. Neither acetate removal nor methylamine increased [Ca2+]i in medium containing 0.1 microM [Ca2+]e, although in both cases pHi increased. We conclude that in bovine anterior pituitary cells NH4Cl raises [Ca2+]i by two independent pathways, increasing net calcium entry and mobilizing Ca2+ from a TRH-insensitive calcium store. PMID- 1906785 TI - Fos-Jun heterodimers and Jun homodimers bend DNA in opposite orientations: implications for transcription factor cooperativity. AB - Association of Fos and Jun with the AP-1 site results in a conformational change in the basic amino acid regions that constitute the DNA-binding domain. We show that Fos and Jun induce a corresponding alteration in the conformation of the DNA helix. Circular permutation analysis indicated that both Fos-Jun heterodimers and Jun homodimers induce flexure at the AP-1 site. Phasing analysis demonstrated that Fos-Jun heterodimers and Jun homodimers induce DNA bends that are directed in opposite orientations. Fos-Jun heterodimers bend DNA toward the major groove, whereas Jun homodimers bend DNA toward the minor groove. Fos and Jun peptides encompassing the dimerization and DNA-binding domains bend DNA in the same orientations as the full-length proteins. However, additional regions of both proteins influence the magnitude of the DNA bend angle. Thus, despite the amino acid sequence similarity in the basic region Fos-Jun heterodimers and Jun homodimers form topologically distinct DNA-protein complexes. PMID- 1906787 TI - Massive overdoses with sustained-release lithium carbonate preparations: pharmacokinetic model based on two case studies. AB - Clinically significant delayed absorption after lithium overdose has been reported previously without adequate explanation. We have studied two patients after they took massive intentional lithium overdoses. The first patient presented shortly after ingesting 74 g of lithium carbonate. Pharmacokinetic analysis with a multicompartmental model of 29 serum lithium concentrations during 300 h (including hemodialysis) established absorption and elimination kinetics. Lithium absorption was both slow (peak concentration 33 h after the initial overdose) and delayed (a second peak occurred at 148 h, 30 h after initiation of oral tube feedings). The delayed absorption of a large fraction of lithium implicated a gastrointestinal drug reservoir. Study of the pharmacokinetics in a second patient, who ingested 98 g of lithium carbonate, provided additional evidence of an endogenous reservoir. This patient's medical management was guided by experience gained from the initial case. Appropriate management for a predicted endogenous drug reservoir may have shortened intensive care and hospitalization. In treating overdoses of sustained-release drug preparations, clinically significant delayed absorption triggered by enteral fluids must be considered as a contributor to delayed absorption. PMID- 1906786 TI - Inhibition of mitomycin C's aerobic toxicity by the seleno-organic antioxidant PZ 51. AB - Mitomycin C (MMC) is a bioreductive alkylating agent that is capable of generating oxygen radicals. Porfiromycin (PM) is an analog to MMC that generates oxygen radicals at a significantly lower level than the parent compound. Under aerobic conditions, the toxicity of MMC to EMT6 cells is 2.5-fold that of PM, whereas hypoxically the two are equitoxic. In the present studies, the protective effect of PZ-51 in combination with NAC was assessed against the dose-dependent toxicity of either MMC or PM under both aerobic and hypoxic conditions. Aerobically, the PZ-51 and NAC combination inhibited the toxicity of MMC at concentrations of between 0.25 and 2 microM but had no effect on PM toxicity. Under hypoxic conditions, the PZ-51 and NAC combination had no effect on either MMC or PM toxicity. These findings support a role for oxygen radical generation in the aerobic toxicity of MMC at clinically relevant doses. PMID- 1906789 TI - Immunohistochemical detection of renal carbonic anhydrase of patients with recurrent urolithiasis. AB - In renal exploratory excisions the isoenzyme C of the carbonic anhydrase was detected in 51 operative treated patients with recurrent urolithiasis and in 6 patients with ren mobilis or stenosis of the ureteral pelvic junction by using the immunohistochemical PAP-method. In the distal tubules and collecting ducts there is an alternating occurrence of cells with small and those with strong reactivity. This correlates with the distribution of mean or principal (P-, small reaction) and intercalated (I-, strong reaction) cells. The number of carbonic anhydrase rich cells and the degree of their cytoplasmic reaction to this enzyme seem to correlate with the ability of the urine to acidify. The patients were divided into four groups according to the mean urine pH estimated for a period of two weeks. The third group with predominantly acid urine (pH less than 5.8) showed a significantly increased number of carbonic anhydrase rich cells (mean = 63% +/- 6, n = 18) as compared to the first group (controls) without urolithiasis and normal urine (pH 5.8-6.8, mean = 46% +/- 8, n = 6) or the second group with urolithiasis and normal urine (pH 5.8-6.8, mean = 46% +/- 8, n = 28). The fourth group with predominant alkaline urine (pH greater than 6.8) showed a significantly decreased number of intercalated cells (mean = 42% +/- 16, n = 5) in comparison to the third group. Indeed, the difference with the control group is not significant but the cytoplasmic reaction of I-cells decreases distinctly in comparison to all other groups. PMID- 1906788 TI - Multicenter evaluation of new enzyme-linked immunoassays of follitropin and lutropin in serum or plasma. AB - Results from a multicenter evaluation of two new enzyme-linked immunosorbent assays [Enzymun-Test for follitropin (FSH) and lutropin (LH)] are presented and compared with results from 11 other commercial immunoassays, radioactive as well as nonradioactive. Enzymun-Test FSH and LH assays are suitable for automated systems and manual applications. The tests were reproducible (CV less than 5%), highly specific, and sensitive enough (less than 0.5 int. unit/L) to measure the hormones directly in almost all patients' samples, except for LH measurements in prepubertal children. We did not find interference by heterophilic antibodies or other factors. A comparison of assays for FSH found very good agreement among all modern two-site assays; competitive immunoassays almost invariably yielded systematically lower results for FSH, probably because of the heterogeneity of the International Reference Preparation (2nd IRP FSH, 78/549). For LH also we found good agreement, with no systematic differences among the various reagents. Guidelines for reference values with the new reagents are given. PMID- 1906790 TI - Pneumonia caused by Mycoplasma pneumoniae infection. AB - The features characterizing pneumonia due to Mycoplasma pneumoniae are described. Typical cases, along with chest radiographs of laboratory-documented cases, are presented. PMID- 1906791 TI - The lack of interaction between temafloxacin and combined oral contraceptive steroids. AB - In view of the considerable debate concerning the possible failure of contraception in women taking broad spectrum antibiotics, we have examined a group of 12 women aged 22-32 in a controlled study. Each woman had been on long term therapy with oral contraceptive steroids (OCS) containing ethynylestradiol (EE2) and levonorgestrel (Ng) for at least 6 months and all were in good general health. Blood samples were taken about 11.0 hours after dosing with their OCS on days 5, 6, 7 and 8 of their contraceptive cycle, for measurement of EE2, Ng, FSH and LH by radioimmunoassay. In addition blood samples were taken on days 19, 20 and 21 of the contraceptive cycle for assay of progesterone concentrations in plasma. The study was repeated in the next cycle of use of their OCS during which they took temafloxacin, a broad spectrum quinolone antibiotic in a dose of 600 mg twice daily for 7 days starting on day 1 of the cycle. All women completed the study satisfactorily as judged by diary cards, tablet counts and plasma temafloxacin concentrations. In the early part of the study some nausea and headaches were seen due to taking temafloxacin on an empty stomach but these effects were not seen when the antibiotic was later given with food. There was no evidence of any interaction between temafloxacin and the OCS. The plasma concentration of EE2 was 61.4 +/- 21.1 pg/ml in the control cycle and 68.5 +/- 26.6 pg/ml in the temafloxacin cycle.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1906792 TI - Morphometric study of the human endometrium following continuous exposure to levonorgestrel released from vaginal rings during 90 days. AB - The effects of vaginal devices releasing levonorgestrel (LNG) at a constant rate of approximately 20 micrograms/24 hrs on the human endometrium were studied in a group of 69 normally menstruating women during a period of 90 days of continuous use. Peripheral blood samples were withdrawn three times weekly starting at day 10 of a pretreatment (control) cycle and then three times weekly from day 60 to 90 of the treatment period. The levels of LNG, estradiol, progesterone and sex hormone binding globulin (SHBG) were analyzed by radioimmunoassay techniques. Endometrial biopsies were obtained in the luteal phase of the pretreatment cycle and on day 84-87 of the treatment period. Increased bleeding occurred in most subjects exposed to the LNG-releasing device; the mean number of bleeding and spotting days was 26.4 +/- 8.9 S.D. which exceeded that found in their control cycle. Morphometric analyses of the endometrial biopsies using 9 quantitative indices, revealed highly significant changes in glands and stroma following the use of the LNG-releasing vaginal device. Irrespective of the circulating steroid levels, the administration of LNG significantly diminished the glandular diameter (p less than 0.001), reduced the volume density of the glands (p less than 0.001) and of the glandular epithelium (p less than 0.001). and modified the ratio glandular epithelium: glands (p less than 0.001). It is concluded that levonorgestrel released at a rate of 20 micrograms/24 hrs, induces characteristic changes in the histologic structure of the human endometrium. Although no simple correlation has been found between any of the endometrial indices and the numbers of bleeding/spotting days or bleeding days, the changes as such may represent biochemical alterations which could be predisposing factors for intermenstrual bleeding and spotting. To prove a causal relationship between morphological and biochemical changes and changes in bleeding patterns, further in-depth studies may be required. PMID- 1906793 TI - Endometrial vascular features prior to and following exposure to levonorgestrel. AB - A study of endometrial vasculature, mast cell numbers and tissue levels of tissue plasminogen activator (tPA) prior to and following exposure to levonorgestrel (20 micrograms/day) administered via a vaginal ring was undertaken. Following exposure to levonorgestrel, significantly fewer arterioles were present in the endometrium. During the early secretory phase of the control cycle, a positive correlation was found between mast cell numbers and progesterone levels. Levonorgestrel-exposed biopsies had significantly higher numbers of vessels with endothelial gaps and haemostatic plugs when compared with early secretory endometrium and significantly higher numbers of haemostatic plugs when compared with mid-late secretory endometrium. During the early secretory phase, the numbers of vessels possessing haemostatic plugs positively correlated with the peripheral blood levels of oestradiol and the number of contracted endothelial cells showed a positive correlation with progesterone levels. In mid-late secretory biopsies, the numbers of vessels with contracted endothelial cells were found to correlate negatively with oestradiol levels and the difference in the levels of contracted endothelial cells between the mid-late secretory endometrium and levonorgestrel-exposed endometrium correlated positively with progesterone levels of post-treatment cycles. PMID- 1906794 TI - Lysosomal enzymes in the human endometrium: a biochemical study in untreated and levonorgestrel-treated women. AB - The activities of four lysosomal enzymes, i.e. N-acetyl-beta-hexosaminidase, acid phosphatase, alpha-D-mannosidase and alpha-L-fucosidase have been measured in extracts of endometrial biopsies from untreated and levonorgestrel-treated women of fertile age. Values were compared with protein and DNA content, as well as with lactate dehydrogenase activity, used as reference constituents. In parallel, organ cultures were established from the same endometrial specimens and the release of lysosomal enzymes into the medium was followed. The human endometrium possesses a rich lysosomal equipment, comparable to that found in the human liver. In the untreated cycles, the activities of lysosomal enzymes show a coordinate response to the hormonal changes, decreasing by about 40% from the proliferative to the mid-late secretory phase. Long-term levonorgestrel treatment causes a marked cytoplasmic atrophy, as shown by decreased protein content and lactate dehydrogenase activity, whereas DNA content remains unchanged. In contrast, N-acetyl-beta-hexosaminidase, one of the most active lysosomal enzymes studied, shows a higher specific activity upon levonorgestrel. In both untreated and treated endometria, the organ cultures provide biochemical evidence for a higher release of N-acetyl-beta-hexosaminidase than of lactate dehydrogenase, indicating active secretion of the lysosomal enzyme. During levonorgestrel treatment, there was no correlation between clinically recognized spotting bleeding patterns and lysosomal enzyme content in, or release from, the endometrium. PMID- 1906795 TI - The human calbindin D28k (CALB1) and calretinin (CALB2) genes are located at 8q21.3----q22.1 and 16q22----q23, respectively, suggesting a common duplication with the carbonic anhydrase isozyme loci. AB - The genes encoding calbindin D28k (CALB1) and calretinin (CALB2), two closely related calcium-binding proteins, were mapped by in situ hybridization to the 8q21.3----q22.1 and 16q22----q23 regions of the human genome, respectively. These localizations match the chromosomal regions where the carbonic anhydrase isozyme gene cluster (CA1, CA2, CA3) and the related gene CA7 have been described, respectively. This suggests a common duplication o the calbindin/calretinin and the carbonic anhydrase ancestral genes. PMID- 1906796 TI - Chromosomal assignment of four rat genes coding for the spermatid-specific proteins proacrosin (ACR), transition proteins 1 (TNP1) and 2 (TNP2), and protamine 1 (PRM1). AB - The genes for proacrosin, protamines, and transition proteins are exclusively expressed in haploid spermatogenic cells. From the analysis of mouse x rat cell hybrids which segregate rat chromosomes, the rat gene for proacrosin (ACR) was assigned to chromosome 7, that for transition protein 1 (TNP1) to chromosome 9, and the genes for transition protein 2 (TNP2) and protamine 1 (PRM1) to chromosome 10. PMID- 1906797 TI - Possibility of ideal blood glucose control by a new oral hypoglycemic agent, N [(trans-4-isopropylcyclohexyl)-carbonyl]-D-phenylalanine (A-4166), and its stimulatory effect on insulin secretion in animals. AB - N-[(trans-4-isopropylcyclohexyl)-carbonyl]-D-phenylalanine (A-4166) revealed a new mode of hypoglycemic action with a more rapid onset and a shorter duration of action than the sulfonylureas (SUs). Hypoglycemic mechanisms and glycemic control benefits were demonstrated in laboratory animals. The stimulatory effect of A 4166 on insulin release, in fasting dogs with a cannula into the portal vein, was more rapid than that of tolbutamide after oral administration. A-4166 stopped the stimulation of insulin secretion very quickly, whereas tolbutamide maintained an elevation in plasma insulin levels for at least 6 hours. In the case of A-4166, a counter-regulatory glucagon response was observed during recovery from hypoglycemia, but it was significantly inhibited by tolbutamide. Hyperglycemia induced by glucose loading was rapidly inhibited by A-4166 in normal rats, in genetically diabetic KK mice and in STZ-induced non-insulin-dependent diabetes mellitus (NIDDM) rats. Also, repeated administration of A-4166 for 2 weeks enhanced insulin secretion in the same manner as a single administration in normal rats. In conclusion, A-4166 is a new type of oral hypoglycemic agent, having a rapid and short-term insulin secretory effect and no suppressive effect on the hypoglycemia-induced glucagon response. Oral therapy with A-4166 would be beneficial in supplementing endogenous insulin secretion and would exert ideal glycemic control in NIDDM patients. PMID- 1906798 TI - Effect of epidemic influenza on ketoacidosis, pneumonia and death in diabetes mellitus: a hospital register survey of 1976-1979 in The Netherlands. AB - The influence of epidemic influenza on hospitalizations because of influenza, pneumonia and diabetic acidosis in patients with diabetes mellitus was investigated. Data on the weekly incidence of influenza-like illness were obtained from the Continuous Morbidity Registration and the cumulative data on hospitalizations in short-stay hospitals were obtained from the National Medical Registration. Patients with duodenal ulcer were used as a control population. Epidemic elevations of influenza infections were observed in 1976 and 1978. The estimated relative risk for hospitalization because of influenza infection was 1.1 and 1.0 for the two non-epidemic years 1977 and 1979, respectively. For the epidemic years 1976 and 1978 this risk was calculated to be 5.7 and 6.2, respectively. An increased relative risk was also noted for pneumonia; being 25.6 for both epidemic years. The estimated relative risk of dying during hospitalization rose from 30.9 in 1977 to 91.8 in 1978. The number of hospitalizations for ketoacidosis was 50% higher in 1978 than in the other three years. During the epidemic years, 25.7% of patients hospitalized for pneumonia died, while this percentage was 14.6% in the non-epidemic years (P less than 0.05). Differences in mortality due to diabetic acidosis were similar: 25.4% in epidemic and 14.7% in non-epidemic years (P less than 0.01). During the 1978 epidemic, one out of every 1300 patients with diabetes mellitus was hospitalized because of pneumonia. It is estimated that 1 of every 260 patients with IDDM was hospitalized for diabetic acidosis. It is concluded that patients with diabetes mellitus have indeed a very high influenza-associated morbidity. PMID- 1906799 TI - [Listeriosis in malignant diseases]. AB - Listeriosis occurred in two patients, a 46-year-old woman and a 41-year-old man, in the course of an underlying malignant disease. The woman had a metastasizing pancreatic apudoma, requiring partial pancreas resection with splenectomy. After the end of cytostatic treatment she developed headaches and fever up to 40 degrees C. Listeria monocytogenes was demonstrated in the blood and cerebrospinal fluid. She went into coma on the day after hospital admission and, despite antibiotic administration, she died on the fourth day of treatment. The 41-year old man was suspected of having an angioimmunoblastic lymphoma. Severe haemolytic anaemia (haemoglobin 4.4 g/dl) was treated with glucocorticoids, massive blood transfusions and splenectomy, at first without success. During immunosuppressive treatment with prednisone and cyclophosphamide the haemoglobin rose. But he was still feverish with nocturnal sweating. Neurological symptoms of motor aphasia, cranial nerve deficits and incomplete hemiparesis rapidly developed. Computed tomography revealed a focus in the internal capsule. Blood culture grew Listeria. The focal encephalitis healed with minor sequelae after antibiotic treatment. Both patients had hypogammaglobulinaemia, but no granulocytopenia. It is stressed that listeriosis should be included in the differential diagnosis in cases of septicaemia or cerebral infection occurring in the course of malignant disease. PMID- 1906800 TI - [Hemostatic disorders in acute and chronic leukemias. Pathogenesis and therapy]. PMID- 1906802 TI - Antimitogenic effects of dexamethasone in chemically transformed mouse fibroblasts. AB - Dexamethasone (a synthetic glucocorticoid) inhibited the entry into the S-phase of quiescent chemically transformed mouse fibroblasts (BP-A31) stimulated with 12 O-tetradecanoyl 13-acetate (TPA; a protein kinase-C activator) or with basic fibroblast growth factor. The basal rate of DNA synthesis was also strongly reduced by dexamethasone. In contrast, the mitogenic activity of insulin (acting via the insulin-like growth factor-I receptor) was little or not at all affected by dexamethasone. The antimitogenic activity of dexamethasone was enhanced when the steroid was included in the culture medium 24 h before the addition of mitogens. The effects of dexamethasone were glucocorticoid specific, partially reversed by the antiglucocorticoid RU 486, and prevented by cycloheximide (suggesting the involvement of glucocorticoid-induced protein synthesis in the antimitogenic activity of dexamethasone). Under the conditions of exponential growth in serum-free medium as well as in the presence of TPA, dexamethasone arrested the proliferation of sparsely seeded cells after a delay of 24-48 h. The BP-A31 cells are known to be constitutively competent and express at quiescence certain genes related to the G0/G1 transition in the original nontransformed A31 cell line. Of the transcripts corresponding to these genes, dexamethasone caused a rapid elimination of the JE mRNA, coding for a protein of the family of cytokines. The cell content of c-jun mRNA was also strongly reduced in the cells incubated at quiescence with dexamethasone (in the absence of mitogen). The presence of TPA along with dexamethasone prevented the elimination of c-jun, but not of JE mRNA. Short (30-min; together with the inducers) or long (24-h) treatment of the cells with dexamethasone did not prevent the induction of the c fos gene expression by either TPA or basic fibroblast growth factor, indicating that dexamethasone does not interfere with mitogenic signal transduction. We conclude that in TPA-stimulated cells, the antiproliferative effect of dexamethasone is not due to interference with the expression of the c-jun gene, but may be related to the decreased level of the JE cytokine mRNA as well as to the synthesis of growth inhibitory protein(s). PMID- 1906801 TI - Photoperiodic differences in in vitro pituitary gonadotropin basal secretion and gonadotropin-releasing hormone responsiveness in the golden hamster. AB - In order to examine pituitary gonadotropin secretion and responsiveness to GnRH after photic-induced changes in reproductive condition, an in vitro pituitary perifusion system was established for male golden hamster tissue. Anterior pituitaries from adult males which had been maintained on 14 h light:10 h dark (long days) or 6 h light:18 h dark (short days) for 10 weeks were perifused using an Acusyst perifusion system. Perfusates from unstimulated tissue (basal secretion) and from tissue stimulated with hourly pulses of GnRH (25, 50, or 100 ng/ml) were assayed for LH and FSH by RIA. Tissue from short-day animals had lower basal LH secretion than tissue from long day animals, but there were no significant photoperiodic differences for GnRH-stimulated LH secretion. In contrast, there were no photoperiodic differences in basal FSH secretion, but tissue from short-day animals secreted more FSH than tissue from long-day animals when stimulated with GnRH. Bioactivity of a small number of perfusate samples was assessed using in vitro rat granulosa cell and mouse Leydig cell assays for FSH and LH, respectively, and did not show any photoperiodic differences in LH or FSH bioactivity for GnRH-stimulated tissue. These studies indicate that the pituitaries of gonadally regressed hamsters are capable in vitro of responding to GnRH with similar or greater levels of gonadotropin release compared to pituitaries from animals with functional gonads. Therefore, it appears that the lowered serum gonadotropin levels seen in vivo in gonadally regressed animals are not due to a reduction in intrinsic pituitary sensitivity to GnRH. PMID- 1906803 TI - Effect of immunoneutralization of neuropeptide Y on gonadotropin and prolactin secretion in normal mice and in transgenic mice bearing bovine growth hormone gene. AB - Immunoneutralization of endogenous neuropeptide Y (NPY) with specific antibodies was used to evaluate the possible physiological role of this neuropeptide in the regulation of gonadotropin and PRL secretion in the mouse. Because regulation of anterior pituitary function can be profoundly altered by chronic GH excess, we felt it was also of interest to have examined the effects of immunoneutralization of NPY in transgenic mice expressing bovine (b) GH gene with mouse metallothionein-I promotor. Intact or castrated transgenic and normal (nontransgenic) littermate adult male mice were injected with control rabbit serum or anti-NPY rabbit serum (anti-NPY). Blood samples were obtained 24 h later for hormone measurements. In intact transgenic mice expressing bGH gene, plasma LH levels were reduced and plasma PRL levels were increased, as compared to their normal littermates. Plasma levels of FSH were similar in normal and transgenic animals. Injection of anti-NPY increased plasma LH levels significantly in both intact normal and intact transgenic mice. However, plasma levels of FSH and PRL were increased significantly after anti-NPY treatment only in intact normal mice. In both normal and transgenic males, castration lead to the expected increase in plasma FSH and LH levels, whereas plasma levels of PRL remained unaltered. Administration of anti-NPY to castrated animals was followed by a significant increase in circulating LH levels in both transgenic and normal mice, whereas plasma levels of PRL were not changed. The results suggest that NPY plays a physiological role in the control of gonadotropin and PRL release in the adult male mouse, and that expression of the bGH gene in transgenic mice is associated with altered role of endogenous NPY in the control of pituitary function. PMID- 1906804 TI - Recombinant expression of human follistatin with 315 and 288 amino acids: chemical and biological comparison with native porcine follistatin. AB - Follistatin is a glycosylated monomeric protein originally isolated from ovarian follicular fluid based on its ability to specifically inhibit pituitary FSH release. To further explore the physiological role of follistatin, we have expressed recombinant human follistatins with 315 (rhFS-315) and 288 (rhFS-288) amino acids in Chinese hamster ovary cells under the control of the simian virus 40 promoter. The two types of FS originated from alternatively spliced mRNAs and rhFS-315 differed from rhFS-288 by having an extra 27-amino acid sequence at the carboxyl-terminal. The yield of the purified rhFS-315 and rhFS-288 after a single step of affinity chromatography on an activin-coupled Affi-Gel column was 3-5 mg/liter conditioned medium. Using the rhFS-315 and rhFS-288 as molecular mass markers, Western blotting with FS carboxyl-terminal-specific antibodies demonstrated that the majority of native FS isolated from porcine ovarian follicular fluid was neither FS-315 nor FS-288, but was composed of 300 amino acids in various forms of glycosylation. This finding is consistent with our earlier results obtained from tryptic peptide fragment analysis of native FS. Only a very small percentage (less than 1%) of native porcine FS was FS-288. In cultures of rat anterior pituitary cells, rhFS-315 (ED50, 115.2 +/- 16.2 pM) is equipotent to native porcine FS (ED50, 86.7 +/- 14.1 pM) on the suppression of FSH release, but, surprisingly, rhFS-288 (ED50, 9.6 +/- 2.2 pM) is 8-10 times more potent than the native protein, similar to the potency of inhibin-A (ED50, 8.6 +/- 0.9 pM). Interestingly, when the in vivo FSH-suppressing activity of rhFS 288 was compared to that of inhibin-A in 1-week ovariectomized adult rats, it was found that rhFS-288 was more potent and longer acting than inhibin-A. Hence, these results indicate that FS-288 is probably one of the most potent natural FSH suppressors. PMID- 1906805 TI - Rapid augmentation of prolactin cell number and secretory capacity by an estrogen induced factor released from the neurointermediate lobe. AB - 17 beta-Estradiol (E2) has been shown to exert an acute stimulatory effect on PRL secretion via an indirect action involving the neurointermediate lobe (NIL). In the present study we used a reverse hemolytic plaque assay to determine whether this effect was manifested as an augmentation of the number of PRL secretors and/or an increase in the amount of hormone released per PRL cell. Cultures of anterior pituitary (AP) and NIL cells from ovariectomized rats were cultured overnight, exposed to the treatment (E2 or vehicle) for 3 h, and then subjected to a reverse hemolytic plaque assay that was carried out in the presence or absence of TRH. Concurrent exposure of AP cells to E2 and NIL cells evoked an 11 12% increase in the overall proportion of PRL-secreting cells. This was true when the AP and NIL cells were incubated as a mixed culture and when the two cell types were maintained in the same petri dish but on separate plastic supports, and TRH did not significantly influence this response. The effect of E2 on the number of PRL secretors was negated when NIL cells were not present throughout the experiment or when they were removed from the cultures just before commencement of E2 treatment. Simultaneous treatment with E2 and NIL cells also significantly augmented the sizes of PRL plaques produced under basal conditions by AP cells. Taken together, these results demonstrate that E2 stimulates NIL cells to release an activity that enhances PRL secretion in two ways: 1) by recruiting additional PRL cells into the secretory pool, and 2) by augmenting the secretory capacity of individual PRL cells. PMID- 1906806 TI - Endogenous opioids mediate the nocturnal prolactin surge in the pregnant rat. AB - Endogenous opioids stimulate PRL release in the rat during proestrus, stress, and lactation. This study investigated the potential role of opioids in regulating the daily nocturnal PRL surges that occur during the first half of pregnancy. On day 8 of pregnancy, infusion of naloxone (NAL; 0.25, 1.0, or 2.0 mg/10 min), an opioid receptor antagonist, from 0100-0400 h blocked the nocturnal surge in a dose-dependent manner. PRL remained at basal levels throughout the infusion when the highest dose of NAL was used. A PRL surge was still present in this group, but its delayed onset occurred 1 h after termination of the NAL infusion. In another experiment NAL was used to determine whether opioids are needed to maintain the nocturnal surge or only to initiate the surge. On day 8 of pregnancy, infusion of NAL (2.0 mg/10 min) was started at 0300 h, after initiation of the surge had occurred, and was continued until 0600 h. After 1 h of infusion, PRL levels were less than 20 ng/ml, compared to more than 200 ng/ml in controls (P less than 0.002) and remained low. A PRL surge occurred approximately 2-3 h after the infusion was discontinued, at a time when the surge was completed in controls (P less than 0.01). Experimental animals did not differ in their surges relative to controls on the next day when no infusion was given. Another set of experiments was performed to determine whether blockade of endogenous opioids inhibited the nocturnal PRL surge by stimulating tuberoinfundibular dopamine (TIDA) neurons. Day 8 pregnant rats infused with NAL (2.0 mg/10 min) from 0100-0400 h demonstrated no nocturnal PRL surge. Subsequently, the medial basal hypothalamus in NAL-treated animals and saline controls was incubated in vitro with the DOPA decarboxylase inhibitor brocresine (100 microM). The greater amount of resultant DOPA accumulation in the stalk median eminence of NAL-treated animals reflected increased TIDA neuronal activity compared to that in SAL-infused controls. Similar results were obtained when rats were treated in vivo with the DOPA decarboxylase inhibitor NSD 1015 (25 mg/kg BW) just before termination of the NAL infusion. Based on these results, we conclude that endogenous opioid peptides are essential in initiating and maintaining nocturnal PRL surges in pregnant rats. Moreover, opioids appear to exert their effects by decreasing TIDA neuronal activity. PMID- 1906807 TI - Continuous infusion with implantable pumps: expanding the radiologist's role. AB - Drug infusion systems attract increasing attention as biomedical technology offers miniaturized devices for targeted delivery of therapeutic substances on an outpatient basis. We have used a totally implantable, subcutaneous pump, externally programmable by radiofrequency link, learning the technique of implantation and management and using various imaging modalities for the diagnosis and control of complications. The procedure for implanting systems for continuous intrathecal analgesia and systemic intravenous chemotherapy is described. Our experience of the latter is made up of 296 implants in 290 patients. The selected infusion pump proved reliable and acceptable to patients and the quality of life, given the reduced drug toxicity, more than good. The complications were few both in frequency and in severity. The setting-up of a long-term infusion system, when major surgery is not needed, can fall within the interventional radiologist's field, partly because of a good cost-benefit ratio. PMID- 1906808 TI - A nationwide collaborative study on the long-term effects of bromocriptine in patients with Parkinson's disease. The fourth interim report. AB - The interim results of the nationwide collaborative study on the long-term effects of bromocriptine in patients with Parkinson's disease are reported. Four years ago, two prospective clinical studies were started to evaluate the long term effects of bromocriptine in Parkinson's disease. The first was to investigate the long-term effects of bromocriptine monotherapy and the second to see the long-term effects of a combination therapy of bromocriptine with levodopa. Patients who had never been treated with levodopa were placed on bromocriptine monotherapy, and those who had been treated with levodopa for not more than 5 years were allocated randomly to either the combination or the levodopa group. Two hundred and eighty-six patients were enrolled in the former study and 416 in the latter. Among the 286 patients, 164 continued for further observation at the end of the fourth year, and 74 of them were still being treated with bromocriptine monotherapy. However, in 78, levodopa had to be added. Among the 416 patients in the second study, 216 were allocated to the combination group and 200 to the levodopa control group. At the end of the fourth year, 130 in the former and 140 in the latter group remained for further observation. In all three groups, a gradual loss of efficacy was noted. The rate of efficacy loss appeared largest in the monotherapy group and smallest in the combination group. Effects on tremor and rigidity are still maintained, but effects on akinesia and gait were lost by the end of the fourth year in all groups. Wearing-off and dyskinesias seem to be better managed by the combination therapy. The incidence of wearing-off was very small in the monotherapy group. No serious side effects were encountered except for 1 patient who died of pulmonary fibrosis in the combination group. PMID- 1906809 TI - Accumulation and spatial location of aldose reductase mRNA in a lens tumor of an alpha A-crystallin/SV40 T antigen transgenic mouse line. PMID- 1906810 TI - Biogenesis of secretory granules. Implications arising from the immature secretory granule in the regulated pathway of secretion. AB - In endocrine cells the regulated secretion of hormones, peptides, enzymes and neurotransmitters into the external medium occurs when mature secretory granules fuse with the plasma membrane. Secretory granules form at the trans-Golgi network (TGN) by envelopment of the dense-core aggregate of regulated secretory proteins by a specific membrane. The secretory granules initially formed at the TGN, referred to here as immature secretory granules, are morphologically and biochemically distinct from mature secretory granules. The functional similarities and differences between the immature secretory granule and the mature secretory granule, and the events involved in the maturation of the secretory granules are briefly discussed. PMID- 1906811 TI - Antithrombin Cambridge II, 384 Ala to Ser. Further evidence of the role of the reactive centre loop in the inhibitory function of the serpins. AB - Four unrelated individuals have been identified with an identical antithrombin variant, associated in one of them with episodes of recurrent venous thromboses. In each case, the plasma antithrombin concentration was normal and the only function abnormality was a minor but consistent decrease in the heparin-induced thrombin inhibition suggesting a mutation at or near the reactive centre of the molecule. Amplification and direct sequencing of exon 6 showed a G----T mutation at nucleotide 1246, which corresponds to a substitution of a serine for an alanine at residue 384. This is one of a series of conserved alanines that form the stalk to the reactive centre loop. The observed changes in this variant are compatible with recent structural studies that infer that mobility of this stalk with partial re-entry into the A-sheet of the molecule is necessary for optimal inhibitory activity. PMID- 1906812 TI - Heterologous in vitro transcription from two archaebacterial promoters. AB - A cell-free extract of Sulfolobus shibatae is able to specifically initiate transcription in vitro at the promoter of the plasmid-encoded gene for the major gas vesicle protein of Halobacterium halobium and at the promoter for the transcript T4 of the temperate H. halobium phage phi H. The corresponding promoter from the virulent phage mutant phi HL1 yields enhanced transcription in the heterologous system, in agreement with strongly increased in vivo expression. PMID- 1906814 TI - Amino acid sequence determination of the novel forms of Go alpha purified from bovine brain membranes. AB - Previously we have reported that there are at least four different forms of Go alpha in bovine brain membranes which can be distinguished by their elution profiles from Mono Q column and their immunological reactivities. The four alpha subunits are referred to as alpha o1, alpha o2, alpha o3 and alpha o4 in their elution orders from the column. Partial amino acid sequences of the purified alpha o1 and alpha o2 were determined and compared with the predicted sequences of two classes of Go alpha cDNAs, termed Go alpha-1 and Go alpha-2. There were at least two unique fragments corresponding with the predicted amino acid sequence of the Go alpha-2 cDNA but different from that of the Go alpha-1 cDNA upon tryptic digestion of alpha o1- or alpha o2-subunit. The alpha o3- and alpha o4 subunits, but not alpha o1-and alpha o2-subunits, were recognized by an antibody raised against a unique amino acid sequence predicted from Go alpha-1 cDNA. These results suggest that alpha o1,2 subunits and alpha o3,4 subunits are encoded by Go alpha-2 cDNA and Go alpha-1 cDNA, respectively. PMID- 1906813 TI - Comparison of mammalian, chicken and Xenopus brain-derived neurotrophic factor coding sequences. AB - We have used the polymerase chain reaction (PCR) to amplify and clone coding sequences of the mature region of brain-derived neurotrophic factor (BDNF) from monkey, rat, chicken and Xenopus genomic DNA. Consistent with previous reports, the predicted amino acid sequences obtained in this manner from monkey and rat were identical to other mammalian BDNF sequences. The chicken and Xenopus BDNF sequences are also highly conserved, but contain 7 and 8 amino acid substitutions, respectively, compared to mammalian BDNF. Comparison of these sequences with the homologous NGF and NT3 coding regions provides further insight into amino acid residues that may be responsible for the different receptor specificities of these factors. PMID- 1906815 TI - Intranasal estradiol administration to oophorectomized women. AB - An open, dose-finding study into the effects of a new intranasal 17 beta estradiol formulation using dimethyl-beta-cyclodextrin as a solubilizer was conducted in nine hysterectomized and oophorectomized patients with symptoms of estrogen deficiency. After nasal delivery of 0.34 mg estradiol in three patients, concentration-time curves of estradiol in serum and its metabolite estrone in plasma were established. High initial estradiol serum levels were found in the order of 5 nmol/l. Estrone/estradiol ratios were below unity, whereas, in contrast, estrone/estradiol ratios after oral administration of estradiol are known to exceed unity. Biological activity, as reflected by suppression of FSH and LH, was manifest. In nine patients symptoms of estrogen deficiency were assessed by a questionnaire. After 3 and 6 months of treatment, a clinically and statistically significant decrease (P less than 0.01) of the total score according to this questionnaire was found compared to the beginning of the study. Thus nasal delivery of estradiol using this cyclodextrin formulation has potential for further clinical evaluation. PMID- 1906816 TI - Coding difficulties in behavioral observation. PMID- 1906817 TI - Meeting needs through integrated care. PMID- 1906818 TI - The single entry model: success through cooperation. PMID- 1906819 TI - A simplified approach to facility accreditation. PMID- 1906820 TI - Hospitals and continuing care: maintaining partnerships. PMID- 1906821 TI - Technology assessment in continuing care. PMID- 1906822 TI - The effects of 2,4-dithiobiuret on sensory and motor function. AB - 2,4-Dithiobiuret (DTB) exposure causes a delayed onset muscle weakness in rats that has been attributed to depressed neuromuscular transmission. The present study compares the effects of DTB on both sensory and motor function in rats. Adult male Long-Evans hooded rats were exposed to saline, 0.25, 0.5, or 1.0 mg/kg/day DTB, ip, for 5 consecutive days (Days 1-5). Body weights were monitored throughout the experiment. Motor activity was measured for 1 hr in figure-eight mazes on Days 0, 6, 13, and 27. Forelimb and hindlimb grip strength were assessed on Days 6, 13, and 27. Auditory thresholds were determined for 5- and 40-kHz tones using reflex modification of the startle response on Days 0, 7, 14, and 28. Visual function was examined on Day 6 in animals exposed at 0.5 mg/kg/day using flash- and pattern-elicited visual evoked potentials (FEPs and PEPs, respectively). Thermal sensitivity was measured using the hot plate procedure. All motor endpoints were decreased in a dosage- and time-dependent manner; the higher the dosage the longer the effects lasted. There were no effects on any measure of sensory function with the exception of peak N2 of the FEP. Both the amplitude and latency of FEP N2 were altered by DTB exposure. Decreases in body weight were maximal on Day 9 at 1.0 mg/kg/day (20% from control), but recovered by Day 22. Motor activity was suppressed on Day 6 only, whereas grip strength measures were decreased on both Days 6 and 13. Auditory thresholds were not significantly altered; however, baseline startle amplitude was decreased at the highest dosage on Days 7 and 14, but recovered by Day 28. Hot plate latencies were not altered by DTB treatment. These data demonstrate that DTB produces a reversible impairment of motor function, without altering auditory, thermal, or pattern visual function. FEP N2, which is thought to arise from activity generated in the superficial layers of visual cortex, was diminished by DTB treatment, indicating that DTB can alter the function of the CNS, although effects on the motor system are more pronounced. PMID- 1906823 TI - Effects of juvenile hormone mimics on larval development and metamorphosis of Drosophila melanogaster. AB - To determine if prolonged larval exposure to juvenile hormone (JH) could influence the decision to metamorphose, Drosophila melanogaster larvae were reared from hatching on medium containing either of the JH mimics, methoprene or 2-[1-methyl-2-(4-phenoxyphenoxy)-ethoxy]-pyridine (S31183). The latter was 23 times more active as a JH mimic in the white puparial assay (ED50 = 0.22 pmole). Larval development and pupariation were unaffected except at 1000 ppm methoprene and 10 ppm or higher S31183 where larval life was prolonged with increased mortality in the second instar. Adult eclosion was prevented by concentrations greater than 1 ppm methoprene and 0.1 ppm S31183. At low concentrations only adult abdominal development was affected, but at the higher concentrations an increasing percentage was blocked at the pupal stage. This latter effect was considerably diminished when the treatment was begun in the mid second instar. The methoprene-resistant mutations, Met1 and Met2, were 10 and 6 times more resistant to S31183 in the white puparial assay and about 20 times more resistant in the larval feeding experiments than the wild-type, indicating that the effects seen are typical of JH. These studies suggest that excess JH may affect adult development of imaginal structures if present at the onset of postembryonic cell proliferation of the imaginal discs or histoblasts. Thus, commitment for adult differentiation must occur early during this proliferative phase. PMID- 1906824 TI - Improved methods for purification of an enterotoxin produced by Bacillus cereus. AB - An enterotoxin (ET) produced by Bacillus cereus was purified by ammonium sulfate precipitation followed by chromatography on SP-Sephadex C-25, chromatofocusing, and gel filtration on Sephacryl S-300. Purified ET was electrophoretically homogeneous with a molecular mass of 45,000 and with an isoelectric point of 5.5. It showed vascular permeability activity in rabbits, was lethal to mice, and caused fluid accumulation in mouse ligated intestinal loops. It showed cytotoxicity to Vero cells, but did not show any hemolytic or phospholipase C activities. These biological activities were found to be easily inactivated by heating at 56 degrees C for 5 min, by digestion with trypsin and pepsin, and by exposure to pH below 3.0 or higher than 11. PMID- 1906826 TI - Consultation-liaison psychiatry in western Europe. The European Consultation Liaison Workgroup. AB - Consultation-liaison psychiatry (C-L) services have developed throughout Europe, largely as a result of individual local initiative. Reviews by contributors from 14 countries reveal similarities in national approaches and in the problems caused by inadequate resources, lack of recognition from psychiatric colleagues, and difficulties in integrating C-L with comprehensive systems of psychiatric care, which are mainly oriented toward community care. National C-L organizations and a recently established European Workgroup have focused attention on the clinical importance of C-L and the need to define national and local policies for its clinical role, staffing, and other resources. There is considerable and increasing interest in European C-L research. PMID- 1906825 TI - Functional analysis of exotoxin A-related protein of Pseudomonas aeruginosa lacking residues 225-412. AB - The crystal structure of the exotoxin A (ETA) of Pseudomonas aeruginosa showed that this protein is folded into three distinct domains. Domain I (Ia and Ib), the amino-terminal domain, is the receptor-binding domain of ETA and domain III, the carboxy-terminal domain, is responsible for the ADP-ribosyl transferase activity of the toxin. To elucidate the function(s) of domains 1b and II in the intoxication process and to define the region of the domain III necessary for ADP ribosylating activity, a defined deletion in the structural gene of P. aeruginosa ETA encompassing residues 225-412 was constructed and an ETA-related product DeID, (from which all of domains II and Ib were deleted) was expressed. The ETA related protein did not penetrate sensitive cells, but retained the same specific activity to ADP-ribosylate elongation factor-2 as wild-type toxin. This suggests that domain II is necessary to allow toxin internalization by sensitive cells and that the absence of domain Ib does not interfere with enzymic activity. The domain strictly involved in ADP-ribosylation activity encompasses residues 412 613. PMID- 1906827 TI - Effects of naphthalene metabolites on cultured cells from eye lens. AB - Naphthalene is toxic to the eye and results in opacification of the lens. To investigate the metabolic events that may be occurring in the lens epithelial cells, a cell line of lens from a transgenic mouse was incubated with various metabolites of naphthalene. Naphthoquinone at 50 microM was toxic to most cells with a depletion of glutathione levels noted within 6 h of incubation. At 10 microM, naphthoquinone caused an increase in specific activity of the enzyme DT diaphorase. This enzyme is thought to be a defense against quinones since semiquinone formation is thought to be lessened. Naphthalene-1,2-dihydrodiol at 50 microM also caused an increase in the specific activity of the DT-diaphorase, while at 10 microM no apparent change occurred in the cells. Although there was evidence of metabolic alterations in the cells with the metabolites of naphthalene, the protein profile by two-dimensional gel electrophoresis did not change and there was no indication of an increase in carbonyl formation in the soluble proteins of the cells. These experiments indicate that the metabolites of naphthalene can cause alteration in the metabolism of the lens cells but may not cause apparent changes in the major proteins within the lens epithelium. PMID- 1906828 TI - An in vitro bacterial model of cytotoxicity to living cells caused by dopamine and 6-hydroxydopamine oxidation at physiological pH. AB - The cytotoxicity of dopamine (DA) and 6-hydroxydopamine (6-OHDA) on living cells, in vitro, has been previously deeply investigated in neuroblastoma cells. This study was designed to explore the possibility to use bacteria as targets for studying DA and 6-HODA cytotoxicity. Both DA and 6-HODA oxidize when added to bacteriological media. The rate of autoxidation of 6-HODA was greater than DA within the first hours. The oxidation-dependent cytotoxicity caused bacterial growth-inhibition and killing at concentration of 10(-4)M. All the bacterial strains tested were slightly more susceptible to DA than to 6-HODA. Antioxidants (sodium metabisulfite, cysteine) prevented the oxidation and abolished the growth inhibitory activity. The addition of exogenous catalase protected the cells against the effect of the oxidation of both the catecholamines up to the concentration of 5 mM, while the addition of exogenous superoxide dismutase protected the cells only at the minimal inhibitory concentrations. Taking into account that some of the results obtained are similar to those previously reported using neuroblastoma cells as targets, the use of bacteria for studying oxygen toxicity from these catecholamines seems to be a potentially useful model system. PMID- 1906829 TI - Abnormal permeability precedes the development of a gluten sensitive enteropathy in Irish setter dogs. AB - Intestinal permeability to 51Cr-EDTA was examined during the development of gluten sensitive enteropathy in dogs bred from affected Irish setters and reared on a normal wheat containing diet. Comparisons were made with litter mates reared on a gluten free diet and with a control group of age matched, clinically healthy Irish setters reared on the normal diet. Studies at 4, 6, 8, and 12 months of age were correlated with morphometric and biochemical examinations of peroral jejunal biopsy specimens. Permeability was increased at all ages in the group fed gluten free diet compared with control dogs, although there were no differences in villus height, intraepithelial lymphocyte density, and alkaline phosphatase activity. At four months, permeability in the normal diet group was greater than in controls, although comparable with that in the gluten free diet group. Permeability in the normal diet group increased further in conjunction with the development of partial villus atrophy and reduced alkaline phosphatase activity, and by 12 months permeability was significantly greater than in their gluten free diet litter mates and the control dogs. The findings suggest that an underlying permeability abnormality may be involved in the pathogenesis of gluten sensitive enteropathy in Irish setter dogs. PMID- 1906830 TI - [Local administration of low-dose estriol and vital Lactobacillus acidophilus in postmenopause]. AB - A randomized double-blind trial with 15 postmenopausal women led to a remarkable result. Local treatment with vaginal tablets just containing 0.03 mg estriol proved to be equivalent to the widely used dosage of 0.5 mg. The test drug Gynoflor E induced significant proliferation of the vaginal epithelium and thus offers the basis for a complete restoration of the vaginal environment. Simultaneously given Lactobacillus acidophilus can be implanted successfully and thus an acid vaginal milieu can be restored. PMID- 1906831 TI - Perineural fibrosis of superficial peroneal nerve complicating ankle sprain: a case report. AB - The peroneal nerve is susceptible to traction injury during inversion ankle sprains. Previously, these traction lesions have been identified only at the fibular neck and popliteal fossa level. This report illustrates a previously unreported condition of perineural fibrosis of the superficial peroneal nerve at the level of the ankle following an inversion ankle sprain. Perineural fibrosis should be considered in the differential diagnosis of patients with persistent pain after ankle sprain. PMID- 1906832 TI - Isolation and properties of a Lyt-2.1-negative mutant of a Lyt-2.1/Lyt-2.2 CTL line. PMID- 1906834 TI - Rapid fluorescent focus inhibition test for rabies antibody estimation using murine neuroblastoma cell line. AB - A rapid fluorescent focus inhibition test (RFFIT) for rabies antibody estimation has been standardized in which murine neuroblastoma cell line, Neuro-2A and tissue culture microtiter plates were used. Serum samples from 105 human beings, 30 canines, 7 rabbits and 4 monkeys were tested by RFFIT. Of these, 33 human and 20 canine sera were also tested by the mouse neutralization test (MNT). Twelve human sera were tested by RFFIT, MNT and ELISA. There was 94 per cent correlation between the results obtained by RFFIT and MNT, while in 6 per cent of the sera tested, the RFFIT was found to be more sensitive than the MNT. PMID- 1906833 TI - Circulating immune complexes in healthy, HIV-antibody positive subjects. AB - The components of the circulating immune complexes (CICs) were characterised in asymptomatic HIV seropositive individuals. Forty four of 214 individuals (20.56%) showed the presence of CICs. Specific HIV anti-HIV CICs were detected in 33 of them (75%). The isotypic specificity of antibodies found to these CICs was measured. IgG and IgA immunoglobulin classes were detected in CICs. PMID- 1906835 TI - Modulation of mycotoxin and nitrosamine carcinogenesis by indole-3-carbinol: quantitative analysis of inhibition versus promotion. AB - The value of chemopreventive agents for reducing human response to mycotoxins and N-nitrosamines remains uncertain, especially since many such agents also can act as tumour promoters. Indole-3-carbinol (I3C) from cruciferous vegetables can inhibit DNA adduction and hepatocarcinogenesis induced by aflatoxin B1 (AFB1) or N-nitroso-diethylamine in trout if given before and with the carcinogen but promotes carcinogenesis when given after initiation. Similar results have been obtained with I3C and AFB1 in rats. In detailed studies using 10,000 trout, inhibition of AFB1 carcinogenesis was found to be saturable at high doses of I3C, approximately proportional to dose of I3C through the range of human intake and, within this range, quantitatively predicted by I3C-mediated reduction of AFB1-DNA adduction in liver. In a second study, post-initiation promotion of AFB1 carcinogenesis was approximately proportional to I3C dose, increased with duration of exposure, decreased with delayed onset of exposure, and reduced but still significant when I3C was given on alternate months or weeks or twice per week only. Hence, promotion by this common component of cruciferous vegetables required prolonged exposure but not necessarily on a daily basis. PMID- 1906836 TI - Effect of long-term feeding of nivalenol on aflatoxin B1-initiated hepatocarcinogenesis in mice. AB - Nivalenol, a trichothecene, occurs widely in cereals and foods; our current two year feeding trial has revealed no tumorigenic activity in female mice. To investigate whether dietary nivalenol modulates the development of aflatoxin B1 (AFB1)-initiated hepatocarcinogenesis, one-week old C57Bl/6 x C3H F1 mice were injected intraperitoneally with 6 mg/kg bw AFB1 and six weeks later fed diets containing 0, 6 or 12 ppm nivalenol for one year. Male mice in all three groups developed hepatocellular carcinomas and adenomas, while the incidences in females were 31% in those given AFB1 alone and 20% and 0 in those given AFB1 with 6 and 12 ppm nivalenol, respectively. These findings indicate that dietary nivalenol suppresses AFB1-initiated hepatocarcinogenesis in female mice, presumably by acting on the promotion step. PMID- 1906837 TI - Aflatoxin B1-DNA binding and aflatoxin B1-glutathione conjugation with isolated hepatocytes from rats and hamsters. AB - Binding of aflatoxin B1 (AFB1) to DNA and AFB1-glutathione conjugation during the metabolism of AFB1 have been examined with freshly isolated hepatocytes from male Fischer rats and Syrian hamsters. Even though there was no significant difference in cytochrome P450 and glutathione contents, there were marked differences in the metabolism of AFB1 (33 nM) in hepatocytes from these two species. Thus, AFB1-DNA binding was six-fold higher in the rat than in hamster hepatocytes, whereas AFB1 glutathione conjugation was 12-fold higher in hamster than in rat hepatocytes. The addition of 0.5 mM diethylmaleate had no significant effect in rats, whereas its presence produced a nine-fold increase in AFB1-DNA binding with 85% inhibition of thiol conjugation in hamster hepatocytes. Styrene oxide (1 mM) produced 50% and 25-fold increases in AFB1-DNA binding in rat and hamster hepatocytes, respectively, with corresponding decreases in thiol conjugation. Triethyltin bromide (50 microM) inhibited both processes by 50% in rat hepatocytes, whereas it produced a nine-fold increase in AFB1-DNA binding with a concomitant decrease in thiol conjugation in hamster hepatocytes. These results suggest that glutathione S-transferases play a more significant role in modulating AFB1-DNA binding in hamster than in rat hepatocytes. PMID- 1906838 TI - Lack of promoting ability of snuff in rats initiated with 4-nitroquinoline-N oxide. AB - In an experiment to evaluate the carcinogenicity and promoting capacity of snuff, a reservoir was created in the lower lip of male Sprague-Dawley rats. Groups of 30 rats were treated with snuff only (twice a day on five days a week), propylene glycol (solvent) three times weekly for four weeks, painting of the hard palate with 4-nitroquinoline-N-oxide (4-NQO) three times weekly for four weeks followed by snuff, 4-NQO only for four weeks, or cotton pellets only (twice a day on five days a week). The experiment was continued up to 108 weeks. High levels of tobacco-specific nitrosamines were found in the snuff (a commercial US brand). Rats treated with snuff only, 4-NQO followed by snuff and 4-NQO only had a significantly higher number of squamous-cell tumours and hyperplastic squamous lesions of the lip, oral and nasal cavity and forestomach than solvent or untreated controls. The total number of neoplasms was significantly higher in rats treated with snuff only and with 4-NQO followed by snuff in comparison to the other groups. Thus, snuff and 4-NQO by themselves can induce benign and malignant tumours. Snuff appears to have a general tumorigenic effect but lacked promoting ability after initiation with 4-NQO. PMID- 1906839 TI - Inhibitory effect of ellagic acid on genotoxicity induced by aflatoxins B1 and G1. PMID- 1906840 TI - Protection of mice from lethal endotoxemia by use of an ornithine-containing lipid or a serine-containing lipid. AB - The effects of an ornithine-containing lipid [alpha-N-(3-acyloxyacyl)-ornithine (Orn-L)] or a serine-containing lipid [alpha-N-(3-acyloxyacyl)-serine (Ser-L)] from Flavobacterium meningosepticum on lethal endotoxemia in mice were examined. When 500 micrograms of Orn-L was intravenously administered 1 h before intravenous administration of a lethal dose of endotoxin, none of the mice died. The protective effect of Ser-L was weaker than that of Orn-L. Light and electron microscopic studies demonstrated that necrosis of hepatocytes caused by endotoxin was prevented by pretreatment with Orn-L. Furthermore, Kupffer cells were activated morphologically 1 h after the administration of Orn-L or Ser-L, and the liposomes of the lipoamino acids were incorporated into phagolysosomes in activated Kupffer cells. The activity of tumor necrosis factor in sera of endotoxin-treated mice was decreased markedly by pretreatment of mice with Orn-L. In vitro, the lipoamino acids suppressed endotoxin-induced tumor necrosis factor generation but did not suppress tumor necrosis factor generation induced by zymosan and whole cells of Staphylococcus aureus. These results suggested that Orn-L and Ser-L can be used as specific blocking agents against endotoxin. The blocking mechanism may be antagonistic, because of the structural similarities between the lipoamino acids and endotoxin lipid A. PMID- 1906841 TI - Effect of mycobacteria on sensitivity to the cytotoxic effects of tumor necrosis factor. AB - Unlike Mycobacterium leprae, Mycobacterium tuberculosis is not found inside cells other than macrophages and polymorphonuclear cells in vivo, yet previous work has revealed that in vitro it readily enters all cell lines tested. Moreover, these cells are not killed by the intracellular mycobacteria. We report here that when fibroblasts take up live (but not killed) M. tuberculosis H37Rv, they develop greatly increased sensitivity to the toxic effects of tumor necrosis factor (TNF) whether the cell line is inherently sensitive to TNF or not. Ultrasonically disrupted M. tuberculosis also has this property. The increased sensitivity is seen in the absence of metabolic inhibitors, although addition of emetine, an inhibitor of protein synthesis, causes the effect to manifest itself earlier and at a lower concentration of TNF. In contrast, infection with Mycobacterium bovis bacillus Calmette-Guerin induces little or no increased sensitivity to TNF, whereas Mycobacterium avium and M. tuberculosis H37Ra have intermediate sensitivities. We discuss the possibility that virulent tuberculosis strains produce a factor which distorts the normal protective function of TNF, rendering it toxic to host tissues and leading to the classical immunopathology of tuberculous lesions. PMID- 1906842 TI - Roles of complement and complement receptor type 3 in phagocytosis of Listeria monocytogenes by inflammatory mouse peritoneal macrophages. AB - Listeria monocytogenes is a facultative intracellular bacterium that is phagocytosed by and can proliferate within cells of the mononuclear phagocyte system. However, the receptors used by macrophages to internalize this organism have not been identified. In the experiments described here, the contributions of serum complement component C3 and macrophage complement receptor type 3 (CR3) to opsonization and phagocytosis of L. monocytogenes by mouse inflammatory peritoneal macrophages were studied. An assay which allowed the distinction of adherent versus internalized bacteria was used to show that following mixing of L. monocytogenes with inflammatory macrophages, greater than 95% of the bacteria bound were internalized by these phagocytes. When immunofluorescent antibodies to C3 and immunoglobulin were used, C3 but not immunoglobulin was detected on L. monocytogenes following incubation in normal serum or ethylene glycol-bis(beta aminoethyl ether)-N,N'-tetracetic acid-Mg(2+)-chelated serum. When macrophages were incubated with 5% serum and L. monocytogenes in a standard assay, approximately 80% of the phagocytosis was inhibited by heat-inactivated serum or by the addition of F(ab')2 anti-C3 antibody. The role of macrophage CR3 was demonstrated by the ability of anti-CR3 monoclonal antibody M1/70 to decrease phagocytosis to the same levels as those seen with heat-inactivated serum. These experiments indicated that in the presence of normal serum, L. monocytogenes is phagocytosed by inflammatory macrophages primarily because CR3 on these cells binds to C3 deposited on the bacterial surface. PMID- 1906843 TI - Selective induction of metabolic activation programs in peritoneal macrophages by lipopolysaccharide substructures. AB - The structural elements of Salmonella typhimurium lipopolysaccharides (LPS) that are able to stimulate peritoneal macrophages to produce increased amounts of prostaglandin E2, ornithine, and citrulline, agents known to modulate immune responses, are described. Two different incomplete lipid A structures which lack the carbohydrate portion, the nonhydroxylated fatty acids lauric acid and myristic acid (lipid A precursor IB), and additional palmitic acid (lipid A precursor IA) stimulated increased prostaglandin E2 synthesis but were unable to augment ornithine and citrulline production at concentrations of up to 0.5 microgram/ml. Acyl-deficient smooth LPS containing lipid A precursors IA and IB substituted by the complete carbohydrate region were able to augment prostaglandin E2 and ornithine production but failed, even at a high concentration (0.5 microgram/ml), to stimulate citrulline production. Moreover, Re glycolipids and smooth intact LPS containing the lipid A region with 3 acyloxyacyl residues possessed all of the structural requirements to induce increased prostaglandin E2, ornithine, and citrulline synthesis. Finally, all of the LPS structures, including lipid A precursors IA and IB stimulated, in combination with gamma interferon, production of citrulline with similar efficiencies. These results demonstrate that LPS contains various substructures including regions of the carbohydrate and lipid A structure that can deliver signals for the activation of peritoneal macrophages. Signals for partial activation of macrophages to produce prostaglandins and ornithine can be delivered by acyl-deficient LPS structures. In contrast, full activation of macrophages to produce citrulline requires an additional signal that is delivered by 3-acyloxyacyl residues of the lipid A region or gamma interferon. PMID- 1906844 TI - Role of tumor necrosis factor in macrophage leishmanicidal activity in vitro and resistance to cutaneous leishmaniasis in vivo. AB - Recombinant human tumor necrosis factor (TNF) and purified murine TNF were both able to activate macrophages to destroy intracellular Leishmania major in vitro. In addition, parasitizing macrophages with L. major markedly increased the ability of the cells to produce TNF. Finally, when mice were vaccinated with an avirulent form of L. major, the animals produced large amounts of TNF but no gamma interferon in response to infection with virulent L. major. Treating these mice with a neutralizing anti-TNF antibody led to partial but not complete inhibition of the resistant state, which suggests that factors other than TNF and gamma interferon contribute to resistance to L. major. PMID- 1906845 TI - Activities of purine catabolism related enzymes in zinc deficiency: relationship to T-lymphocyte dysfunction and hyperammonemia. AB - The activities of liver, muscle, and red blood cell enzymes involved in the degradation of purine were assayed in zinc deficient (ZD), pair-fed control (PF) and ad libitum-fed control (Ad lib) rats. Diets (1.5 ppm of zinc in ZD diet and 110 ppm in control diet) were fed to rats for 6 weeks after which they were sacrificed and tissues isolated for several assays. Results indicated a significant increase in the concentration of plasma NH3 (P less than .0005) and uric acid (P less than .05), and a decrease in the concentration of blood urea nitrogen (BUN) (P less than .025) in ZD rats compared to both control groups. The activities of liver and red blood cell (RBC) nucleoside phosphorylase (NPase) were lower (P less than .025) in ZD rats. Activity of 5'adenosine monophosphate deaminase (AMPDA) was higher in liver (P less than .0001) and muscle (P less than .01) in ZD groups vs. controls. Activity of hypoxanthine polyribosyl transferase (HPRT) in liver was higher (P less than .005) in ZD group compared to controls. The present findings could be viewed from two aspects: first, they provide an insight into the specific role of zinc on T-lymphocyte function which is believed to be mediated by the regulatory effect of zinc on the enzyme nucleoside phosphorylase and, second they provide a possible mechanism for hyperammonemia observed in zinc deficient human subjects and experimental animals. PMID- 1906846 TI - Immunohistochemical staining for chondroitin sulphate and keratan sulphate. An evaluation of two monoclonal antibodies. AB - Immunohistochemical staining with commercially available antibodies against chondroitin sulphate (clone CS-56) and keratan sulphate (clone 1/20/5-D-4) was compared with two conventional histochemical methods for the demonstration of glycosaminoglycans, namely Alcian Blue with varying pH and critical electrolyte concentrations, and a modified PAS stain. The antibodies were tested on sections from both frozen and fixed, paraffin embedded human material from umbilical cord, skin, and bronchus. The results showed immunostaining to function equally well on frozen and routine sections, and to be superior to Alcian Blue and PAS with regard to morphological detail. Thus, reactivity with anti-chondroitin sulphate was demonstrated in vessel walls, in small nerves, in the basal membrane zone of the skin, in perichondrium, and in and around chondrocytes. Reactivity with anti keratan sulphate occurred in chondroid matrix and in perichondrial tissue; however, some cells of the bronchial epithelium and mucous glands also exhibited positivity. PMID- 1906847 TI - A new form of specific targeting cancer immunotherapy using anti-tumor monoclonal antibody-conjugated lymphokine-activated killer cells. AB - Cross-linking of effector T cells to target cancer cells augments their tumor lytic activities. Here we describe a new method of conjugating lymphokine activated killer (LAK) cells with cancer-specific monoclonal antibody. The LAK cells were biotinylated, treated with avidin, and conjugated with biotinylated monoclonal antibody. These monoclonal antibody-conjugated LAK cells showed specifically enhanced killing activities against anti-tumor antibody-reactive cancer cells, and cold target cells specifically inhibited their activities. PMID- 1906849 TI - Promoting effect of sodium chloride solution mist on the induction of papillomas on Syrian hamster tracheal mucosa following administration of diethylnitrosamine. AB - The promoting effect of NaCl solution mist was studied in the induction of papillomas on Syrian hamster trachea following single subcutaneous injection of diethylnitrosamine (DEN). Sixty male hamsters were divided into three groups. Group A; Exposure to a 5% NaCl solution mist for 32 weeks following single subcutaneous injection of DEN at a dose of 3 mg/100 g body weight. Group B; Subcutaneous DEN injection alone. Group C; Exposure to the NaCl mist for 32 weeks alone. Total numbers of papillomas on the trachea in each group were 107 in group A, 64 in group B, and 0 in group C (P less than 0.05 between group A and B, P less than 0.01 between either groups A or B and C). Comparing the incidence of large papillomas with a diameter of more than 2 mm, that in group A hamsters was significantly greater than that of group B (22 large papillomas vs. 8 large papillomas, P less than 0.01). No difference in the effects on the epithelial cells of the nasal cavity, the bronchial or the alveolar cells in the lung was recognized between groups A and B. The hamsters in group C were not observed to have any changes in any of the respiratory organs. Inhalation of NaCl solution mist is considered to have a promoting effect on the induction of papillomas in the hamster trachea following DEN injection. PMID- 1906848 TI - Work-related bladder cancer risks in male Japanese workers: estimation of attributable fraction and geographical correlation analysis. AB - One hundred and forty-nine relative risks (RRs) on occupations and bladder cancer were extracted from 27 case-control studies and geometric means were calculated for 27 occupations as summary RRs. Those in high risk occupations, among whom the summary RRs significantly exceeded unity, were found to be petroleum workers (RR = 3.51), dye workers (RR = 3.38), machinists (RR = 2.76), drivers (RR = 2.22), rubber workers (RR = 2.19), printers (RR = 2.12), clothing/tailors (RR = 2.10), wood workers/carpenters (RR = 1.70), miners (RR = 1.68), textile workers (RR = 1.63), mechanics (RR = 1.54), engineers (RR = 1.54), leather workers (RR = 1.49), painters (RR = 1.48) and chemical workers (RR = 1.44). The estimated numbers of male bladder cancers in 1980 in the high risk and other occupations were 820 and 2065 cases, respectively. The estimated number of work-related bladder cancer was 548 cases, the attributable fraction being 19% in active employees and 12% in the entire population. The geographical distribution of male bladder cancer deaths in Japan was positively correlated with the distributions of workers in the transport/communications industry and in tertiary industries including services, wholesale, retail, finance and insurance, whereas it was negatively correlated with the distribution of workers in the agricultural industry. These findings suggest that workers in certain industries may be at high risk of bladder cancer, but lifestyle modification associated with urbanization and industrialization could be an alternative explanation. PMID- 1906850 TI - Modifying effects of various chemicals on preneoplastic and neoplastic lesion development in a wide-spectrum organ carcinogenesis model using F344 rats. AB - Modifying potentials of various chemicals on tumor development were investigated in a wide-spectrum organ carcinogenesis model using male F344/DuCrj rats. The animals were treated with N-nitrosodiethylamine (100 mg/kg body weight, ip, single injection at the commencement of the study), N-methyl-N-nitrosourea (20 mg/kg body weight, ip, 4 times during weeks 1 and 2) and N-bis(2 hydroxypropyl)nitrosamine (0.1% in drinking water, during weeks 3 and 4) for multi-organ initiation and then were given one of 14 test chemicals including 6 hepatocarcinogens, 7 non-hepatocarcinogens and 1 non-carcinogen, or basal diet for 16 weeks. All rats were killed at the end of week 20, and the major organs were carefully examined for preneoplastic and neoplastic lesions. Immunohistochemical demonstration of glutathione S-transferase-positive foci was also used for quantitative assessment of liver preneoplastic lesion development. Modifying effects were shown for 11 out of 14 test agents in the liver, forestomach, glandular stomach, lung, urinary bladder or thyroid, 7 of them targeting more than two organs. This was the first demonstration to our knowledge that clofibrate possesses enhancing potential for urinary bladder carcinogenesis and an inhibiting effect on thyroid carcinogenesis. Caprolactam showed no effect in any organ, in agreement with its established inactivity. The results indicated that the system could be reliably applied as a medium-term multiple organ bioassay for assessment of the modification potential of test agents in unknown target sites. PMID- 1906851 TI - Time- and dose-dependent induction of invasive urinary bladder cancers by N-ethyl N-(4-hydroxybutyl)nitrosamine in B6C3F1 mice. AB - A sequential investigation of N-ethyl-N-(4-hydroxybutyl)nitrosamine (EHBN) bladder carcinogenesis was performed in male B6C3F1 mice maintained ad libitum on tap water containing 0.025% EHBN for 4, 12, 20, 28 and 36 weeks. A total of 81 invasive tumors, comprising 55 squamous cell carcinomas (SCCs) (68%), 25 transitional cell carcinomas (TCCs) (31%) and 1 adenocarcinoma (1%) were found. Of these, 23 (22 SCCs and 1 TCC) demonstrated invasion to the prostate, 3 metastasized to the lung, and 2 spread by peritoneal seeding. The anaplastic grade and extent of invasion of the SCCs significantly exceeded those of the TCCs. The results suggested a histogenetic pathway from simple dysplasia through papillary or nodular dysplasia and/or carcinoma in situ to eventual development of invasive carcinomas. PMID- 1906852 TI - Sex differences in o-phenylphenol and sodium o-phenylphenate rat urinary bladder carcinogenesis: urinary metabolites and electrolytes under conditions of aciduria and alkalinuria. AB - F344 male and female rats were administered 1.25% o-phenylphenol (OPP) or 2% sodium o-phenylphenate (Na-OPP) in combination with 3% NaHCO3 or 1% NH4Cl for 8 weeks and changes in the urinary bladder histopathology and the urinary components were examined. Administration of OPP with NaHCO3 resulted in marked urothelial hyperplasia in the urinary bladder of male rats, the response being less pronounced in females. OPP alone exerted no proliferative effect and NaHCO3 induced only slight hyperplasia in males. Na-OPP alone induced mild hyperplastic lesions only in males, this being completely prevented by concomitant administration of NH4Cl. The findings thus demonstrated a clear correlation between hyperplastic response and reported carcinogenic potential of these treatments. Of the urinary factors examined, increases in levels of pH and sodium ion concentration were positively associated with proliferative lesions especially in males, although the findings failed to explain the sex difference. Urinary concentrations of non-conjugated forms of OPP metabolites were also not directly correlated with the development of hyperplasias. Thus, changes in individual urinary factors presumably affect urothelial proliferation in combination rather than separately. The presence of OPP metabolites, including 2 phenyl-1,4-benzoquinone, in the urine may be unimportant in the OPP urinary carcinogenesis even under conditions of alkalinuria and high sodium ion concentration. PMID- 1906853 TI - Cytosolic-nuclear tumor promoter-specific binding protein: association with the 90 kDa heat shock protein and translocation into nuclei by treatment with 12-O tetradecanoylphorbol 13-acetate. AB - Suspension-cultured HeLa cells possess a cytosolic-nuclear tumor promoter specific binding protein (CN-TPBP) which lacks protein kinase C activity. This CN TPBP existed in cytosol of HeLa cells, but translocated into nuclear fraction of the cells after treatment of the cells with 12-O-tetradecanoylphorbol 13-acetate (TPA). The translocation of CN-TPBP induced by TPA became apparent within 10 min after the treatment with TPA, and was completed within 3 h. CN-TPBP bound TPA with the association constant of 1.4 x 10(10) M-1, and also bound teleocidin B, debromoaplysiatoxin, and thapsigargin in a mutually competitive manner. The binding affinity order of synthetic analogs of teleocidin B correlated with the adhesion-inducing potency order of the compounds toward human leukemia cell line HL-60. The apparent molecular weight of CN-TPBP under non-denaturing conditions was estimated to be 66-68 kDa. CN-TPBP forms a complex with the 90 kDa heat shock protein, and the complex was stabilized by the presence of molybdate. These characteristics of CN-TPBP are similar to those of the nuclear receptors of glucocorticoid and dioxin. These findings suggested that CN-TPBP acts as a nuclear receptor for tumor promoters, and that tumor promoters may exert their biological effects by binding to CN-TPBP. PMID- 1906854 TI - Methylation and expression of human pepsinogen genes in normal tissues and their alteration in stomach cancer. AB - In normal human tissues, pepsinogen A mRNA was expressed only in the fundic mucosa of the stomach, whereas pepsinogen C mRNA was expressed in all regions of the stomach mucosa and also in the proximal duodenal mucosa. The distributions of these mRNAs were consistent with those of pepsinogens A and C in the gastroduodenal mucosa. Methylation analysis of DNAs from normal tissues with methylation-sensitive restriction enzymes, HpaII and HhaI, revealed that pepsinogen A and C genes are hypomethylated in tissues producing pepsinogens A and C, suggesting a role of DNA methylation in the regulation of the differential expression of the genes for the two human pepsinogens during normal differentiation. In stomach cancer tissues and cancer cell lines, the expressions of the pepsinogen genes were decreased or lost, in good accordance with their pepsinogen productions. No gross structural changes of the pepsinogen genes were observed in these cancers, but the methylation patterns of the pepsinogen genes were found to be altered in different ways in different cancers. The functional significance of the altered methylation is unknown; however, these results suggest that considerable heterogeneity of the methylation patterns occurs in human stomach cancers. PMID- 1906855 TI - Characterization of a 54 kDa, alpha 1-antitrypsin-like protein isolated from ascitic fluid of an endometrial cancer patient. AB - A protein factor which stimulated [3H]thymidine uptake into free hepatocytes prepared from normal mouse liver was detected in the ascitic fluid of gynecological cancer patients. The factor was subsequently further purified from the ascitic fluid of an endometrial cancer patient by DEAE-Sephacel, Sephadex G 150 and Phenyl-Sepharose CL-4B column chromatographies, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) showed a single protein band of 54,000 Da, designated tentatively as 54K ascitic protein (54K-AP). 54K-AP was similar to human alpha 1-antitrypsin (alpha 1-AT) in terms of SDS-PAGE and immunological behavior, but was slightly different in terms of amino acid sequence and isoelectric point. Although 54K-AP inhibited the activities of bovine trypsin and alpha-chymotrypsin as did human alpha 1-AT, 54K-AP inhibited the plasminogen activator released from human endometrial cancer Ishikawa cells more efficiently than alpha 1-AT. Because, in contrast to normal serum, the serum from the endometrial cancer patients stimulated [3H]thymidine uptake into hepatocytes, the possibility arises that 54K-AP could be produced by the cancer host as a defence mechanism against the cancer. PMID- 1906857 TI - Toxicological and tumoricidal evaluations of a new platinum complex, (-)-(R)-2 aminomethylpyrrolidine(1,1-cyclobutanedicarboxylato+ ++)platinum( II) monohydrate, in rats. AB - The toxicities and antitumor activity of a new anticancer platinum compound, (-) (R)-2-aminomethylpyrrolidine(1,1-cyclobutanedicarboxylato++ +) platinum(II) monohydrate (DWA2114R), were examined in rats by single intravenous injection in comparison with those of cis-diammine(1,1-cyclobutanedicarboxylato)platinum(II) (CBDCA) and cis-diamminedichloroplatinum(II) (CDDP). The lethal dose (LD) of DWA2114R (100 mg/kg) or CBDCA (80 mg/kg) caused a slight decrease in body weight (less than 10%) and no significant change in the levels of blood urea nitrogen and urinary sugar and protein. In contrast, a sub-LD level of CDDP (8 mg/kg) seriously decreased body weight (20%) and markedly elevated the levels of these nephrotoxicity parameters. Monitoring the numbers of peripheral blood cells for 3 weeks after the drug injection revealed that all three drugs showed severe thrombocytopenia, moderate leukopenia and slight anemia. However, CBDCA induced the most severe thrombocytopenia among these drugs. The number of platelets was reduced by 60% in rats injected with a half LD of CBDCA. A moderate reduction in platelet count (35-43%) was caused by an equitoxic dose of DWA2114R or CDDP, but abated about 3 days faster than that caused by CBDCA. Interestingly, only CDDP caused an irreversible anemia. Each drug showed a potent antitumor activity at weakly toxic doses against Walker 256 carcinosarcoma transplanted intramuscularly into rats. These results indicate that DWA2114R could be a promising new platinum anticancer agent with an improved toxicity profile. PMID- 1906856 TI - Rapid growth and spontaneous metastasis of human germinal tumors ectopically transplanted into scid (severe combined immunodeficiency) and scid-nudestreaker mice. AB - Xenograft acceptance, growth and spontaneous metastasis of ectopically transplanted human germinal tumors were compared among scid mice, athymic nude mice and F2 hybrids constructed from scid and nude mice, in relation to the impairments of T and B cell functions in these mice. In scid mice which are deficient in T and B cell functions, human yolk sac tumor (YST-2) that originated from the ovary grew to enormous sizes in 100% of the animals after both subcutaneous and intraperitoneal transplantation, while only half (59.1% and 51.9%) of the subcutaneous and none of the intraperitoneal transplants were accepted in usual athymic nude mice (BALB/c-nu/nu and CD1-nu/nu). The YST-2 grew rapidly in scid mice, developing 3 to 10 times larger tumors compared to nude streaker (AKR/J-nustr/nustr) and usual nude mice, respectively. Furthermore, ectopically transplanted tumors spontaneously metastasized to distant organs (mostly to the lung) in scid mice (but less frequently in leaky scid mice), while metastases have never been found in nude mice. Although a xenograft of human classic (typical or pure) seminoma of the testis has never been established in nude mice, it grows slowly in one-third (36.4%) of scid mice and very rapidly in all of scid-nustr (scid/scid; nustr/nustr) double mutant mice. Spontaneous metastases of xenografted seminomas were also observed in distant organs (lymph node, lung, liver, spleen, and kidney). The metastastic distribution of the two human germinal tumors in scid and scid-nustr mice mimics that found in human. These results (xenograft acceptance, growth of transplanted tumors and degree of metastatic spread) were compatible with the level of T and B cell impairments indicated by FACS analysis, as well as mitogen responses, serum IgG and morphological features of the thymus. PMID- 1906859 TI - Late quinolone resistance in Pseudomonas aeruginosa. PMID- 1906858 TI - Kinin-generating cascade in advanced cancer patients and in vitro study. AB - The role of the bradykinin-generating system in the pathogenesis of cancer was explored by simultaneously measuring plasma prekallikrein (PK), the precursor of kallikrein, which is the major enzyme responsible for kinin generation, and plasma kininogens (KNG), which are precursors of kinin, in patients with various cancers. The mean value of plasma PK in healthy volunteers was 2.5 +/- 0.5 (mean +/- SD) units/mg plasma protein and that in cancer patients (all stage IV) was 1.7 +/- 0.7 units/mg plasma protein. The mean value of plasma KNG in healthy volunteers was 12.5 +/- 2.0 ng kinin equivalents/mg plasma protein and that in cancer patients was 10.9 +/- 2.8 ng. These data showed that plasma PK and plasma KNG values were significantly lower in cancer patients compared with healthy volunteers (P less than or equal to 0.005 for PK; 0.0005 less than P less than or equal to 0.005 for KNG; n = 28 for healthy subjects; n = 29 for cancer patients). These data appear to indicate that conversion of PK to kallikrein would probably occur with concomitant consumption of KNG by newly generated kallikrein for kinin generation in cancer patients. Early stage cancer patients showed little difference from healthy volunteers. For the in vitro study, activation of purified Hageman factor (HF) and PK was examined by using cancer cell lines and virus-transformed cells that produced plasminogen activator (PA) at a high rate. Both HF and PK were activated in the presence of plasminogen. Diploid cell lines and primary fibroblasts, which did not produce PA, activated neither HF nor PK. Taking all these data together, we conclude that kinin generation does occur in the plasma of patients with advanced cancer, and that one of the initiation mechanisms of the kinin-generating cascade appears to be mediated by plasmin and to depend on cancer cell-derived PA activity. PMID- 1906860 TI - An evaluation of the susceptibility patterns of gram-negative organisms isolated in cancer centres with aminoglycoside usage. AB - This study in 12 cancer treatment centres across the United States was designed to evaluate the potential for increased resistance to amikacin with unrestricted use. An initial 3-month baseline period during which the use of amikacin was restricted and that of tobramycin and gentamicin unrestricted was followed by a period of at least 12 months when amikacin was the primary aminoglycoside. Resistance of Gram-negative bacilli to these aminoglycosides from hospitalized patients was monitored and compared for the two periods. Amikacin usage increased from a mean of 20.1% to a mean of 83.9% of aminoglycoside patient-days. A reduction in the use of tobramycin and gentamicin were observed with means of 66.1 and 10%, and 13.9 and 6.1%, respectively for the two periods. Resistance to amikacin was 0.85% at baseline and 1.3% at end-point which was not clinically significant (P = 0.614). Baseline resistance was 6.5 and 7.6%, while final resistance was 2.6 and 4.8%, respectively for tobramycin (P = 0.001) and gentamicin (P = 0.052). PMID- 1906861 TI - Clinical and pharmacokinetic study of a single daily dose of amikacin in paediatric patients with severe gram-negative infections. AB - The efficacy and safety of a single 20 mg/kg daily dose of amikacin was studied in an open, uncontrolled trial in 56 infants and children. Most of the patients suffered from severe Gram-negative infection which had failed to respond to previous antibacterial therapy. Amikacin was given in combination with a beta lactam antibiotic in 43 cases, with other antibiotics in five cases and monotherapy in eight cases. Pseudomonas aeruginosa was the most frequently isolated organism (27 cases). Clinical results were satisfactory in 98% of the infections treated. Two patients died, one from the infection and the other 8 weeks after therapy from unrelated causes. Amikacin serum concentrations were high during the first hour after iv infusion, low after 8 h and undetectable at 24 h. Nephrotoxicity and ototoxicity was not detected in any patient. Amikacin when used as a single daily dose in combination with a beta-lactam antibiotic was effective and safe in treating infants and children with severe Gram-negative infection. PMID- 1906862 TI - Single daily dosing of amikacin in an in-vitro model. AB - The pharmacodynamics of amikacin given as a single daily dose was compared with standard divided dosing in an in-vitro model of infection. This model allows the exposure of log phase bacteria to changing concentrations of antibiotics that simulate the kinetics of the drugs in human patients. Two strains of Pseudomonas aeruginosa, one sensitive and one resistant to azlocillin were studied (MICs for amikacin were 16 and 8 mg/l respectively). Simulated drug regimens included: amikacin 400 mg q 8 h; amikacin 1.2 g q 24 h; and azlocillin 4 g q 12 h. Each regimen alone and both combinations of amikacin plus azlocillin were studied. With both amikacin regimens initial rapid killing was followed by regrowth of resistant subpopulations. Azlocillin alone produced minimal killing of the resistant strain and moderate killing with ultimate bacteriostasis of the susceptible strain. Bacterial regrowth was prevented with both combination regimens with the single daily dose of amikacin plus azlocillin producing the most rapid and complete killing, especially of the azlocillin resistant strain. These data support further clinical studies of single daily dosing of aminoglycosides. PMID- 1906863 TI - Efficacy of once- and thrice-daily dosing of aminoglycosides in in-vitro models of infection. AB - The bactericidal efficacy of amikacin, isepamicin and netilmicin was studied against Pseudomonas aeruginosa and Serratia marcescens over a treatment period of 30 h using two one-compartment in-vitro models with differently designed culture compartments. High bacterial inocula were exposed to fluctuating drug concentrations, simulating human serum concentrations (t1/2 = 2 h) during clinical treatment. The same daily dose was administered as 1 h infusions given every 8 h or every 24 h, resulting in peak concentrations of 8 and 24 mg/l for netilmicin, and 24 and 72 mg/l for amikacin and isepamicin, respectively. Once daily dosing was more bactericidal during initial treatment in the in-vitro models (P less than 0.01) and at least as effective as thrice-daily dosing in preventing bacterial regrowth, despite a prolonged period of subinhibitory drug concentration before administration of the second dose. Lower ratios of peak concentration to MIC were needed to achieve bactericidal activity (greater than 99.9% reduction of cfu) after 24 h treatment against S. marcescens compared with P. aeruginosa (P less than 0.01). All nine regimens providing peaks of at least four times the MIC were bactericidal against S. marcescens after 24 h exposure. In contrast, a bactericidal effect against P. aeruginosa occurred only during two of six experiments with peaks of four to nine times the MIC. Similar results were obtained in both in-vitro models of infection. These data suggest insufficient intrinsic activity of the aminoglycosides studied for single drug treatment of P. aeruginosa in the absence of host-defence mechanisms. PMID- 1906864 TI - Comparative kinetics and efficacy of amikacin administered once or twice daily in the treatment of systemic gram-negative infections. AB - In an open randomized study the safety, efficacy and kinetics of a twice-daily amikacin (7.5 mg/kg bd) regimen (group A) was compared with a once-daily dosage (15 mg/kg) schedule (group B). Thirty patients were enrolled in each group. They were suffering from urinary tract infections (37), respiratory tract infections (17), soft-tissue infections (3), exacerbation of chronic prostatitis (1), acute cholangitis (1) and abdominal abscess (1). Aggravating factors were present in 77% and 60% of the groups respectively. The pathogens isolated included strains of various Enterobacteriaceae (53) and Pseudomonas aeruginosa (10) In 76.7 vs 97% (P less than 0.05) the clinical result was satisfactory with pathogen eradication in 80 vs 86.7%. However, there were proportionately more patients in the 7.5 mg/kg bd regimen with respiratory tract infection (40 vs 13%) and fewer patients with urinary tract infections (40 vs 80%). Mild and transient nephrotoxicity and ototoxicity was observed in five and three patients respectively. More patients in group B had amikacin trough concentrations less than or equal to 5 mg/l and peak levels greater than 40 mg/l (P less than 0.001) as well as serum bactericidal titres greater than or equal to 1:16 (P less than 0.05) without significant serum amikacin accumulation over time. It is concluded that amikacin administered once daily is well tolerated and provides better serum bactericidal activity than the twice-daily regimen. PMID- 1906865 TI - Synergistic post-antibiotic effect of amikacin and beta-lactam antibiotics on Enterococcus faecalis. AB - The in-vitro post-antibiotic effect (PAE) of amikacin alone and in combination with ceftazidime, ceftriaxone and piperacillin was studied for two strains of Enterococcus faecalis using a bioluminescent assay of bacterial ATP. The two strains of E. faecalis were resistant to amikacin, ceftazidime and ceftriaxone but sensitive to piperacillin. The bacterial cultures were incubated with the beta-lactam antibiotics for 1 h and concentrations of amikacin between 2-64 mg/l were then added. Thereafter, incubation continued with the combinations for one more hour. After dilution, regrowth was monitored by measuring bacterial ATP every hour. Increasing concentrations of amikacin (2-64 mg/l), ceftazidime (8-32 mg/l) and ceftriaxone (32-128 mg/l) resulted in little or no PAE (0-0.3 h) on these strains. PAEs of 0.5 to 1.6 h resulted from exposure to piperacillin (4-32 mg/l). In combination amikacin and piperacillin increased the PAE to 5.5 h. A synergistic PAE was also seen when the enterococci were exposed to amikacin combined with ceftazidime or ceftriaxone in concentrations close to the MICs of the latter antibiotics. PMID- 1906866 TI - The rpsD gene, encoding ribosomal protein S4, is autogenously regulated in Bacillus subtilis. AB - Although the mechanisms for regulation of ribosomal protein gene expression have been established for gram-negative bacteria such as Escherichia coli, the regulation of these genes in gram-positive bacteria such as Bacillus subtilis has not yet been characterized. In this study, the B. subtilis rpsD gene, encoding ribosomal protein S4, was found to be subject to autogenous control. In E. coli, rpsD is located in the alpha operon, and S4 acts as the translational regulator for alpha operon expression, binding to a target site in the alpha operon mRNA. The target site for repression of B. subtilis rpsD by protein S4 was localized by deletion and oligonucleotide-directed mutagenesis to the leader region of the monocistronic rpsD gene. The B. subtilis rpsD leader exhibits little sequence homology to the E. coli alpha operon leader but may be able to form a pseudoknotlike structure similar to that found in E. coli. PMID- 1906867 TI - Analysis of transcriptional control of the gerD spore germination gene of Bacillus subtilis 168. AB - The gerD locus of Bacillus subtilis comprises a single gene whose function is essential for the germination of B. subtilis spores in media containing asparagine, glucose, and fructose. The expression of gerD has been characterized by using a chromosomal lacZ fusion to the gerD promoter. The promoter is switched on at the same time as the synthesis of glucose dehydrogenase, 2.5 h after sporulation has been initiated in the developing forespore. The gerD gene is not expressed in spoIIB or spoIIIA, -IIIB, -EIII, -FIII, or -IIIG mutants, but it is expressed in spoIIIC and -IIID and spoIVA mutant backgrounds. The in vivo transcriptional start point of the gene has been mapped by primer extension analysis, and sequences upstream from the start point show considerable homology with the promoter consensus sequences recognized by RNA polymerase containing the forespore-specific sigma factor sigma G (E sigma G). gerD is transcribed in vitro by E sigma G with a similar if not identical start point to that found in vivo, and expression of the gene can be rapidly induced in vegetative cells following the induction of sigma G synthesis. These results indicate that gerD is another member of the sigma G regulon, which includes a number of genes expressed only in the forespore compartment of sporulating cells of B. subtilis. PMID- 1906869 TI - Expression of the iap gene coding for protein p60 of Listeria monocytogenes is controlled on the posttranscriptional level. AB - Expression of the iap gene of Listeria monocytogenes encoding a major extracellular protein (p60) was analyzed. Different start sites for transcription of the iap gene were identified by primer extension analysis in L. monocytogenes and in a recombinant Escherichia coli clone. The mutant RIII of L. monocytogenes represents a member of the frequently occurring L. monocytogenes R mutants, which form cell chains and produce greatly reduced amounts of p60. However, the concentrations of iap-specific mRNA were similar in mutant RIII and the wild-type strain. The introduction of additional copies of the iap gene from wild-type L. monocytogenes led to an equal increase of iap mRNA in both strains, but overexpression of protein p60 was only observed in the wild-type strain. The nucleotide sequences of both iap genes and their 5' noncoding regions were identical in all parts that are essential for efficient transcription of the iap gene, translation of the iap-specific mRNA, and transport of the p60 protein. These data suggest that the expression of the iap gene in L. monocytogenes is controlled on the posttranscriptional level by a specific factor that is defective in mutant RIII. PMID- 1906870 TI - Isolation and characterization of catabolite repression control mutants of Pseudomonas aeruginosa PAO. AB - Independently controlled, inducible, catabolic genes in Pseudomonas aeruginosa are subject to strong catabolite repression control by intermediates of the tricarboxylic acid cycle. Mutants which exhibited a pleiotropic loss of catabolite repression control of multiple pathways were isolated. The mutations mapped in the 11-min region of the P. aeruginosa chromosome near argB and pyrE and were designated crc. Crc- mutants no longer showed repression of mannitol and glucose transport, glucose-6-phosphate dehydrogenase, glucokinase, Entner Doudoroff dehydratase and aldolase, and amidase when grown in the presence of succinate plus an inducer. These activities were not expressed constitutively in Crc- mutants but exhibited wild-type inducible expression. PMID- 1906872 TI - Replacement recombination in Lactococcus lactis. AB - In the pUC18-derived integration plasmid pML336 there is a 5.3-kb chromosomal DNA fragment that carries the X-prolyl dipeptidyl aminopeptidase gene (pepXP). The gene was inactivated by the insertion of an erythromycin resistance determinant into its coding sequence. Covalently closed circular DNA of pML336 was used for the electrotransformation of Lactococcus lactis. In 2% of the erythromycin resistant transformants the pepXP gene was inactivated by a double-crossover event (replacement recombination) between pML336 and the L. lactis chromosome. The other transformants in which the pepXP gene had not been inactivated carried a Campbell-type integrated copy of the plasmid. Loss of part of the Campbell-type integrated plasmid via recombination between 1.6-kb nontandem repeats occurred with low frequencies that varied between less than 2.8 x 10(-6) and 8.5 x 10(-6), producing cells with a chromosomal structure like that of cells in which replacement recombination had taken place. PMID- 1906868 TI - Genetic and physical analyses of the growth rate-dependent regulation of Escherichia coli zwf expression. AB - Growth rate-dependent regulation of the level of Escherichia coli glucose 6 phosphate dehydrogenase, encoded by zwf, and 6-phosphogluconate dehydrogenase, encoded by gnd, is similar during steady-state growth and after nutritional upshifts. To determine whether the mechanism regulating zwf expression is like that of gnd, which involves a site of posttranscriptional control located within the structural gene, we prepared and analyzed a set of zwf-lacZ protein fusions in which the fusion joints are distributed across the glucose 6-phosphate dehydrogenase coding sequence. Expression of beta-galactosidase from the protein fusions was as growth rate dependent as that of glucose 6-phosphate dehydrogenase itself, indicating that regulation does not involve an internal regulatory region. The level of beta-galactosidase in zwf-lac operon fusion strains and the level of zwf mRNA from a wild-type strain increased with increasing growth rate, which suggests that growth rate control is exerted on the mRNA level. The half life of the zwf mRNA mass was 3.0 min during growth on glucose and 3.4 min during growth on acetate. Thus, zwf transcription appears to be the target for growth rate control of the glucose 6-phosphate dehydrogenase level. PMID- 1906871 TI - Anaerobic regulation of transcription initiation in the arcDABC operon of Pseudomonas aeruginosa. AB - The arcDABC operon of Pseudomonas aeruginosa encodes the enzymes of the arginine deiminase pathway, which is inducible under conditions of oxygen limitation and serves to generate ATP from arginine. The 5' end of arc mRNA extracted from anaerobically grown cells was determined by S1 and primer extension mapping. The transcription initiation site was located upstream of the arcD gene and 41.5 bp downstream of the center of the sequence TTGAC....ATCAG. This sequence, termed the ANR box, is similar to the consensus FNR recognition site of Escherichia coli. Transcription of the arc operon in P. aeruginosa was strongly decreased by a deletion of the TTGAC half site or by a mutation in the anr gene, which is known to code for the FNR-like regulatory protein ANR. During a transition from aerobic to anaerobic growth conditions, the concentrations of arc mRNAs and the levels of the ArcD and ArcA proteins rose in a parallel fashion. Mutational analysis of the arc promoter region led to the conclusion that the distance between the ANR box and the -10 promoter region is important for promoter strength, whereas the -35 region does not appear to be critical for arc promoter function. These findings and previous results indicate that anaerobic induction of the arc operon occurs at the level of transcription and requires the ANR box in cis and the ANR protein in trans. PMID- 1906873 TI - Effects of mutant small, acid-soluble spore proteins from Bacillus subtilis on DNA in vivo and in vitro. AB - alpha/beta-type small, acid-soluble spore proteins (SASP) of Bacillus subtilis bind to DNA and alter its conformation, topology, and photochemistry, and thereby spore resistance to UV light. Three mutations have been introduced into the B. subtilis sspC gene, which codes for the alpha/beta-type wild-type SASP, SspCwt. One mutation (SspCTyr) was a conservative change, as residue 29 (Leu) was changed to Tyr, an amino acid found at this position in other alpha/beta-type SASP. The other mutations changed residues conserved in all alpha/beta-type SASP. In one (SspCAla), residue 52 (Gly) was changed to Ala; in the second (SspCGln), residue 57 (Lys) was changed to Gln. The effects of the wild-type and mutant SspC on DNA properties were examined in vivo in B. subtilis spores and Escherichia coli as well as in vitro with use of purified protein. Both SspCwt and SspCTyr interacted similarly with DNA in vivo and in vitro, restoring much UV resistance to spores lacking major alpha/beta-type SASP, causing a large increase in plasmid negative supercoiling, and altering DNA UV photochemistry from cell type to spore type. In contrast, SspCAla had no detectable effect on DNA properties in vivo or in vitro, while SspCGln had effects intermediate between those of SspCAla and SspCwt. Strikingly, neither SspCAla nor SspCGln bound well to DNA in vitro. These results confirm the importance of the conserved primary sequence of alpha/beta-type SASP in the ability of these proteins to bind to spore DNA and cause spore UV resistance. PMID- 1906874 TI - Primary structure, expression in Escherichia coli, and properties of S-adenosyl-L methionine:uroporphyrinogen III methyltransferase from Bacillus megaterium. AB - A Bacillus megaterium DNA fragment encoding S-adenosyl-L methionine:uroporphyrinogen III methyltransferase (SUMT) activity was subcloned and sequenced. The encoded polypeptide showed more than 43.5% strict homology to Pseudomonas denitrificans SUMT (F. Blanche, L. Debussche, D. Thibaut, J. Crouzet, and B. Cameron, J. Bacteriol. 171:4222-4231, 1989). The B. megaterium polypeptide was overexpressed in Escherichia coli, partially purified, and shown to exhibit, like P. denitrificans SUMT, substrate inhibition at uroporphyrinogen III concentrations above 0.5 microM, suggesting a common regulation for aerobic cobalamin-producing organisms. PMID- 1906875 TI - Deamination of deoxycytidine nucleotides by the obligate intracytoplasmic bacterium Rickettsia prowazekii. AB - Thymidylate biosynthesis via the methylation of dUMP is required for DNA replication in Rickettsia prowazekii, an obligate intracytoplasmic bacterium. In theory, dUMP synthesis could occur either by the deamination of deoxycytidine nucleotides or by the reduction of uridine nucleotides. Accordingly, the incorporation of both radiolabeled cytidine and uridine into the thymidylate of R. prowazekii was examined. After DNA hydrolysis and high-performance liquid chromatography, it was determined that 85% of the rickettsial thymidylate was derived from cytidine and the remaining 15% was derived from uridine. These findings were supported by the identification of a dCTP deaminase activity in extracts of R. prowazekii. Extracts of R. prowazekii deaminated 1.7 +/- 0.3 nmol of dCTP/min/mg of protein (a value calculated to suffice for rickettsial growth), and no measurable activity was observed with dCMP as the substrate. PMID- 1906876 TI - In vitro identification of a soluble protein:geranylgeranyl transferase from rat tissues. AB - The gamma subunit of mammalian trimeric G proteins has been shown previously to be modified in vivo on a cysteine residue situated at the carboxyl-terminal sequence-Cys-Ala-Ile-Leu-COOH by a 20-carbon prenyl moiety geranylgeranyl (Mumby, S. M., Casey, P. J., Gilman, A. G., Gutowski, S., and Sternweis, P. C. (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 5873-5877; Yamane, H. K., Farnsworth, C. C., Xie, H., Howald, W., Fung, B. K-K., Clarke, S., Gelb, M. H., and Glomset, J. A. (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 5866-5872). A biotinylated peptide acceptor comprising the eight carboxyl-terminal amino acids of the gamma subunit and tritiated geranylgeranyl diphosphate were utilized to monitor a protein:prenyl transferase activity in rat organs of varying age. The transferase activity was dependent upon the presence of divalent metal ions and maximal activity was achieved with either 1 mM ZnCl2 or 20 mM MgCl2. Activity was shown to be linear with respect to time, protein concentration, substrate concentration, and the pH optimum was 7.5. Protein:geranylgeranyl transferase activity was detected in all rat organs studied with the highest specific activity in brain S100. No activity was detected in the membrane fraction. The specific activity in brain, liver, kidney, and heart increased with age. Radioactivity incorporated into the peptide acceptor from both [1 3H]geranylgeranyl diphosphate and [5-3H]mevalonate by 21-day-old rat brain S100 was released by treatment with methyl iodide, and in both cases, analysis of the cleavage products by reversed phase high performance liquid chromatography showed a peak of radioactivity co-eluting with a geranylgeraniol standard which was well resolved from a farnesol standard. This indicated that the rat brain S100 contained not only the protein:geranylgeranyl transferase but also geranylgeranyl synthetase activity and that the peptide acceptor was specific for geranylgeranyl under the conditions tested. PMID- 1906877 TI - Molecular characterization of a unique von Willebrand disease variant. A novel mutation affecting von Willebrand factor/factor VIII interaction. AB - von Willebrand factor (vWF) plays a central role in blood coagulation, mediating the adhesion of the initial platelet plug to the subendothelium, and serving as the carrier for factor VIII (FVIII) in the circulation. In previous studies, we have mapped the epitope for an anti-vWF monoclonal antibody which inhibits the interaction between FVIII and vWF to a region spanning Thr78 to Thr96 of the mature protein (Bahou, W.F., Ginsburg, D., Sikkink, R., Litwiller, R., and Fass, D. N. (1989) J. Clin. Invest. 84, 56-61). We now report the identification of a mutation within this region of vWF that results in decreased FVIII binding. Sequence analysis of polymerase chain reaction amplified platelet vWF mRNA from a von Willebrand disease (vWD) patient with a disproportionately low FVIII level identified a single nucleotide substitution (G----A), resulting in the conversion of Arg91----Gln. Recombinant vWF carrying this substitution showed decreased binding to FVIII compared with wild-type vWF or vWF carrying a polymorphic substitution in the same region (Arg89----Gln). These observations suggest a critical role for Arg91 in the interaction of vWF with FVIII and identify the molecular mechanism for a variant of vWD associated with unusually low FVIII levels. PMID- 1906878 TI - Structure of a fucose-branched chondroitin sulfate from sea cucumber. Evidence for the presence of 3-O-sulfo-beta-D-glucuronosyl residues. AB - The structure of a unique focose-branched chondroitin sulfate isolated from the body wall of a sea cucumber was examined in detail. This glycosaminoglycan contains side chain disaccharide units of sulfated fucopyranosyl units linked to approximately one-half of the glucuronic acid moieties through the O-3 position of the acid. The intact polysaccharide is totally resistant to chondroitinase degradation, whereas, after defucosylation, it is partially degraded by the enzyme. However, only after an additional step of desulfation, the chondroitin from sea cucumber is almost totally degraded by chondroitinase AC or ABC. This result, together with the methylation and NMR studies of the native and chemically modified polysaccharide, suggest that besides the fucose branches, the sea cucumber chondroitin sulfate contains sulfate esters at position O-3 of the beta-D-glucuronic acid units. Furthermore, the proteoglycan from the sea cucumber chondroitin sulfate is recognized by anti-Leu-7 monoclonal antibody, which specifically recognizes 3-sulfoglucuronic acid residues. In analogy with the fucose branched units, the 3-O-sulfo-beta-D-glucuronosyl residues are resistant to chondroitinase degradation. Regarding the position of the glycosidic linkage and site of sulfation in the fucose branches, our results suggest high heterogeneity. Tentatively, it is possible to suggest the preponderance of disaccharide units formed by 3,4-di-O-sulfo-alpha-L-fucopyranosyl units glycosidically linked through position 1----2 to 4-O-sulfo-alpha-L-fucopyranose. Finally, the presence of unusual 4/6-disulfated disaccharide units, together with the common 6-sulfated and non-sulfated units, was detected in the chondroitin sulfate core of this polysaccharide. PMID- 1906879 TI - Biosynthetic maturation of an ascites tumor cell surface sialomucin. Evidence for O-glycosylation of cell surface glycoprotein by the addition of new oligosaccharides during recycling. AB - Previous biosynthetic studies of the ascites 13762 rat mammary adenocarcinoma cell surface sialomucin ASGP-1 (ascites sialoglycoprotein-1) showed that it is synthesized initially as a poorly glycosylated immature form, which is converted to a larger premature form (t1/2 30 min) and more slowly to the mature glycoprotein (t1/2 greater than 4 h). In the present study O-glycosylation of ASGP-1 polypeptide is shown to occur in two phases: an early phase complete in less than 30 min, which corresponds to the synthesis of the premature form, and a later phase that continues for hours and corresponds to the synthesis of the mature form. Pulse-chase labeling studies indicate that 95% of the ASGP-1 has moved to the cell surface in 2 h. Since transit to the cell surface is faster than the slow phase of addition of new oligosaccharides, some new oligosaccharides must be added after ASGP-1 has reached the cell surface. Initiation of new oligosaccharides on cell surface ASGP-1 was demonstrated directly using a biotinylation procedure to identify cell surface molecules. Glucosamine labeling of biotinylated ASGP-1 was shown to occur on galactosamine residues, which are linked to the polypeptide, establishing the addition of new oligosaccharides to the cell surface molecules. Finally, resialylation studies indicate that ASGP-1 rapidly recycles through a sialylating compartment. From these results we propose that ASGP-1 reaches the cell surface in an incompletely glycosylated state and that additional oligosaccharides are added to the glycoprotein in a second process involving recycling. PMID- 1906880 TI - Thermostable alanine racemase of Bacillus stearothermophilus. Construction and expression of active fragmentary enzyme. AB - Limited proteolysis studies on alanine racemase suggested that the enzyme subunit is composed of two domains (Galakatos, N. G., and Walsh, C. T. (1987) Biochemistry 26, 8475-8480). We have constructed a mutant gene that tandemly encodes the two polypeptides of the Bacillus stearothermophilus enzyme subunit cleaved at the position corresponding to the predicted hinge region. The mutant gene product purified was shown to be composed of two sets of the two polypeptide fragments and was immunologically identical to the wild-type enzyme. The mutant enzyme, i.e. the fragmentary alanine racemase, was active in both directions of the racemization of alanine. The maximum velocity (Vmax) was about half that of the wild-type enzyme, and the Km value was about double. Absorption and circular dichroism spectra of the fragmentary enzyme were similar to those of the wild type enzyme. An attempt was made to separately express in Escherichia coli a single polypeptide corresponding to each domain, but no protein reactive with the antibody against the wild-type alanine racemase was produced. Therefore, it is suggested that the two polypeptide fragments can fold into an active structure only when they are co-translated and that they correspond to structural folding units in the parental polypeptide chain. PMID- 1906881 TI - Mobilization of calcium by inositol trisphosphates from permeabilized rat parotid acinar cells. Evidence for translocation of calcium from uptake to release sites within the inositol 1,4,5-trisphosphate- and thapsigargin-sensitive calcium pool. AB - D-myo-Inositol (1,4,5)-trisphosphate ((1,4,5)IP3)-induced Ca2+ release and subsequent Ca2+ reuptake were investigated in saponin-permeabilized rat parotid acinar cells. Following the rapid release of Ca2+ by (1,4,5)IP3, Ca2+ was resequestered. The sequential addition of submaximal concentrations of (1,4,5)IP3 resulted in sequential Ca2+ release. However, when the cells were challenged with the poorly metabolized (1,4,5)IP3 analogues, (1,4,5)IPS3 or (2,4,5)IP3, or under conditions where the metabolism of authentic (1,4,5)IP3 was reduced, Ca2+ reuptake again occurred, but sequestered Ca2+ was not released by subsequent additions of (1,4,5)IP3. The sequestered Ca2+ was, however, released by thapsigargin, an agent which inhibits active Ca2+ uptake into the (1,4,5)IP3 sensitive pool. Furthermore, the rate of thapsigargin-induced release was significantly increased in the continued presence of an (1,4,5)IP3 stimulus. Thus, Ca2+ reuptake apparently occurred into the (1,4,5)IP3- and thapsigargin sensitive Ca2+ store and (1,4,5)IP3 continued to influence the permeability of this pool to Ca2+ during Ca2+ reuptake. In contrast to the findings in permeabilized cells, Ca2+ reuptake did not occur in the sustained presence of (1,4,5)IP3 in intact parotid cells. We conclude that cell permeabilization reveals a kinetic, and presumably structural, separation of Ca2+ uptake and release sites within the (1,4,5)IP3-regulated intracellular organelle. PMID- 1906883 TI - Kinetics for formate dehydrogenase of Escherichia coli formate-hydrogenlyase. AB - Kinetic parameters of the selenium-containing, formate dehydrogenase component of the Escherichia coli formate-hydrogenlyase complex have been determined with purified enzyme. A ping-pong Bi Bi kinetic mechanism was observed. The Km for formate is 26 mM, and the Km for the electron-accepting dye, benzyl viologen, is in the range 1-5 mM. The maximal turnover rate for the formate-dependent catalysis of benzyl viologen reduction was calculated to be 1.7 x 10(5) min-1. Isotope exchange analysis showed that the enzyme catalyzes carbon exchange between carbon dioxide and formate in the absence of other electron acceptors, confirming the ping-pong reaction mechanism. Dissociation constants for formate (12.2 mM) and CO2 (8.3 mM) were derived from analysis of the isotope exchange data. The enzyme catalyzes oxidation of the alternative substrate deuterioformate with little change in the Vmax, but the Km for deuterioformate is approximately three times that of protioformate. This implies formate oxidation is not rate limiting in the overall coupled reaction of formate oxidation and benzyl viologen reduction. The deuterium isotope effect on Vmax/Km was observed to be approximately 4.2-4.5. Sodium nitrate was found to inhibit enzyme activity in a competitive manner with respect to formate, with a Ki of 7.1 mM. Sodium azide is a noncompetitive inhibitor with a Ki of about 80 microM. PMID- 1906882 TI - A mutation in the human apolipoprotein A-I gene. Dominant effect on the level and characteristics of plasma high density lipoproteins. AB - Epidemiologic and genetic data suggest an inverse relationship between plasma high density lipoprotein (HDL) cholesterol and the incidence of premature coronary artery disease. Some of the defects leading to low levels of HDL may be a consequence of mutations in the genes coding for HDL apolipoproteins A-I and A II or for enzymes that modify these particles. A proband with plasma apoA-I and HDL cholesterol that are below 15% of normal levels and with marked bilateral arcus senilis was shown to be heterozygous for a 45-base pair deletion in exon four of the apoA-I gene. This most likely represents a de novo mutation since neither parent carries the mutant allele. The protein product of this allele is predicted to be missing 15 (Glu146-Arg160) of the 22 amino acids comprising the third amphipathic helical domain. The HDL of the proband and his family were studied. Using anti-A-I and anti-A-II immunosorbents we found three populations of HDL particles in the proband. One contained both apoA-I and A-II, Lp(A-I w A II); one contained apoA-I but no A-II, Lp(A-I w/o A-II); and the third (an unusual one) contained apoA-II but no A-I. Only Lp(A-I w A-II) and (A-I w/o A-II) were present in the plasma of the proband's parents and brother. Analysis of the HDL particles of the proband by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed two protein bands with a molecular mass differing by 6% in the vicinity of 28 kDa whereas the HDL particles of the family members exhibited only a single apoA-I band. The largely dominant effect of this mutant allele (designated apoA-ISeattle) on HDL levels suggests that HDL particles containing any number of mutant apoA-I polypeptides are catabolized rapidly. PMID- 1906884 TI - Voltage-dependent modulation of ion binding and translocation in the cardiac Na(+)-Ca2+ exchange system. AB - The transport of Na+ and Ca2+ ions in the cardiac Na(+)-Ca2+ exchanger can be described as separate events (Khananshvili, D. (1990) Biochemistry 29, 2437 2442). Thus, the Na(+)-Na+ and Ca(2+)-Ca2+ exchange reactions reflect reversible partial reactions of the transport cycle. The effect of diffusion potentials (K(+)-valinomycin) on different modes of the Na(+)-Ca2+ exchanger (Na(+)-Ca2+, Ca(2+)-Ca2+, and Na(+)-Na+ exchanges) were tested in reconstituted proteoliposomes, obtained from the Triton X-100 extracts of the cardiac sarcolemmal membranes. The initial rates of the Nai-dependent 45Ca-uptake (t = 1 s) were measured in EGTA-entrapped proteoliposomes at different voltages. At the fixed values of voltage [45 Ca]o was varied from 4 to 122 microM, and [Na]i was saturating (150 mM). Upon varying delta psi from -94 to +91 mV, the Vmax values were increased from 9.5 +/- 0.5 to 26.5 +/- 1.5 nmol.mg-1.s-1 and the Km from 17.8 +/- 2.5 to 39.1 +/- 5.2 microM, while the Vmax/Km values ranged from only 0.53 +/- 0.08 to 0.73 +/- 0.17 nmol.mg-1.s-1.microM-1. The equilibrium Ca(2+) Ca2+ exchange was voltage sensitive at very low [Ca]o = [Ca]i = 2 microM, while at saturating [Ca]o = [Ca]i = 200 microM the Ca(2+)-Ca2+ exchange became voltage insensitive. The rates of the equilibrium Na(+)-Na+ exchange appears to be voltage insensitive at saturating [Na]o = [Na]i = 160 mM. Under the saturating ionic conditions, the rates of the Na(+)-Na+ exchange were at least 2-3-fold slower than the Ca(2+)-Ca2+ exchange. The following conclusions can be drawn. (a) The near constancy of the Vmax/Km for Na(+)-Ca2+ exchange at different voltages is compatible with the ping-pong model proposed previously. (b) The effects of voltage on Vmax of Na(+)-Ca2+ exchange are consistent with the existence of a single charge carrying transport step. (c) It is not yet possible to clearly assign this step to the Na+ or Ca2+ transport half of the cycle although it is more likely that 3Na(+)-transport is a charge carrying step. Thus, the unloaded ion-binding domain contains either -2 or -3 charges (presumably carboxyl groups). (d) The binding of Na+ and Ca2+ appears to be weakly voltage-sensitive. The Ca(2+)-binding site may form a small ion-well (less than 2-3 A). PMID- 1906885 TI - Interaction of glutathione transferase from horse erythrocytes with 7-chloro-4 nitrobenzo-2-oxa-1,3-diazole. AB - 7-Chloro-4-nitrobenzo-2-oxa-1,3-diazole reacts with two thiol groups of the dimeric horse erythrocyte glutathione transferase at pH 5.0, with strong inactivation reversible on dithiothreitol treatment. The inactivation kinetic follows a biphasic pattern, similar to that caused by other thiol reagents as recently reported. Both S-methylglutathione and 1-chloro-2,4-dinitrobenzene protect the enzyme from inactivation. Analysis of the reactive SH group containing peptide gives the sequence Ala-Ser-Cys-Leu-Tyr, identical with that of the peptide that contains the reactive cysteine 47 of the human placental transferase. In the presence of glutathione, the enzyme is not inactivated by this reagent, but it catalyzes its conjugation to glutathione. At higher pH values, 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole reacts with 2 tyrosines/dimer and lysines, as well as with cysteines. Reaction with lysine seems essentially without effect on activity; whether the reactive tyrosines are important for activity could not be determined using this reagent only. However, 2 tyrosines among the 4 that are nitrated by tetranitro-methane are important for activity. PMID- 1906886 TI - The effect of glycoprotein IIb-IIIa receptor occupancy on the cytoskeleton of resting and activated platelets. AB - The platelet integrin, glycoprotein IIb-IIIa (GPIIb-IIIa), serves as the receptor for fibrinogen. This study examined what effect GPIIb-IIIa receptor occupancy had on the cytoskeleton of resting and activated platelets. Triton X-100-insoluble residues (cytoskeletons) were isolated from resting washed platelets incubated with either 500 microM RGDS or 500 microM RGES and examined for protein content. RGDS did not increase the amount of GPIIb-IIIa associated with the cytoskeletal residues which sedimented at either 15,800 x g or 100,000 x g. To determine the effect of receptor occupancy on the formation of the activated platelet cytoskeleton, stirred and nonstirred RGDS-treated platelets in plasma were activated with ADP. Triton X-100-insoluble residues were isolated and examined for both protein content and retention of GPIIb-IIIa. Further, morphological studies were performed on the RGDS-ADP-stimulated platelets. The results of this study suggest that 1) RGDS peptide receptor occupancy does not lead to GPIIb-IIIa linkage to the cytoskeleton, 2) ADP-stimulated platelet shape change, polymerization of actin, and association of myosin with the cytoskeleton are unaffected by RGDS peptide receptor occupancy. 3) RGDS inhibits an aggregation dependent incorporation of ABP, alpha-actinin, talin, and GPIIb-IIIa into the Triton-insoluble residue. PMID- 1906887 TI - The influence of oxidatively modified low density lipoproteins on expression of platelet-derived growth factor by human monocyte-derived macrophages. AB - Platelet-derived growth factor (PDGF) is secreted by several cells that participate in the process of atherogenesis, including arterial wall monocyte derived macrophages. Macrophages in human and non-human primate lesions have recently been demonstrated to contain PDGF-B chain protein in situ. In developing lesions of atherosclerosis, macrophages take up and metabolize modified lipoproteins, leading to lipid accumulation and foam cell formation. Oxidatively modified low density lipoproteins (LDL) have been implicated in atherogenesis and have been demonstrated in atherosclerotic lesions. The effects of the uptake of various forms of modified LDL on PDGF gene expression, synthesis, and secretion in adherent cultures of human blood monocyte-derived macrophages were examined. LDL oxidized in a cell-free system in the presence of air and copper inhibited the constitutive expression of PDGF-B mRNA and secretion of PDGF in a dose dependent fashion. Oxidatively modified LDL also attenuated lipopolysaccharide induced PDGF-B mRNA expression. These changes were unrelated to the mechanism of lipid uptake and the degree of lipid loading and were detectable within 2 h of exposure to oxidized LDL. The degree of inhibition of both basal and lipopolysaccharide-induced PDGF-B-chain expression increased with the extent of LDL oxidation. Monocyte-derived macrophages exposed to acetylated LDL or LDL aggregates accumulated more cholesterol than cells treated with oxidized LDL, but PDGF expression was not consistently altered. Thus, uptake of a product or products of LDL oxidation modulates the expression and secretion of one of the principal macrophage-derived growth factors, PDGF. This modulation may influence chemotaxis and mitogenesis of smooth muscle cells locally in the artery wall during atherogenesis. PMID- 1906888 TI - Binding of tissue-type plasminogen activator by the mannose receptor. AB - Previous studies have shown that tissue-type plasminogen activator (t-PA) in blood is cleared by the liver partially through a mannose-specific uptake system. The present study was undertaken to investigate, in a purified system, whether t PA is recognized by the mannose receptor which is expressed on macrophages and liver sinusoidal cells. The mannose receptor was isolated and purified from bovine alveolar macrophages and migrated as a single protein band at Mr 175,000 on polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. Ligand blotting revealed that this protein specifically bound t-PA. The t-PA receptor interaction was further characterized in a binding assay, which showed saturable binding with an apparent dissociation constant of 1 nM. t-PA binding required calcium ions and was negligible in the presence of EDTA or at acid pH. Mannose-albumin was an effective inhibitor, whereas galactose-albumin did not have a significant effect. From a series of monosaccharides tested, D-mannose and L-fucose were the most potent inhibitors, N-acetyl-D-glucosamine was a moderate inhibitor, whereas D-galactose and N-acetyl-D-galactosamine were ineffective. t PA, deglycosylated by endoglycosidase H, did not interact with the receptor. It is concluded that the mannose receptor specifically binds t-PA, probably through its high mannose-type oligosaccharide. PMID- 1906890 TI - Resolution of a low molecular weight G protein in neutrophil cytosol required for NADPH oxidase activation and reconstitution by recombinant Krev-1 protein. AB - Activation of the membrane-associated NADPH oxidase in intact human neutrophils requires a receptor-associated heterotrimeric GTP-binding protein that is sensitive to pertussis toxin. Activation of this NADPH oxidase by arachidonate in a cell-free system requires an additional downstream pertussis toxin-insensitive G protein (Gabig, T. G., English, D., Akard, L. P., and Schell, M. J. (1987) (J. Biol. Chem. 262, 1685-1690) that is located in the cytosolic fraction of unstimulated cells (Gabig, T. G., Eklund, E. A., Potter, G. B., and Dykes, J. R. (1990) J. Immunol. 145, 945-951). In the present study, immunodepletion of G proteins from the cytosolic fraction of unstimulated neutrophils resulted in a loss of the ability to activate NADPH oxidase in the membrane fraction. The activity in immunodepleted cytosol was fully reconstituted by a partially purified fraction from neutrophil cytosol that contained a 21-kDa GTP-binding protein. Purified human recombinant Krev-1 p21 also completely reconstituted immunodepleted cytosol whereas recombinant human H-ras p21 or yeast RAS GTP binding proteins had no reconstitutive activity. Rabbit antisera raised against a synthetic peptide corresponding to the effector region of Krev-1 (amino acids 31 43) completely inhibited cell-free NADPH oxidase activation, and this inhibition was blocked by the synthetic 31-43 peptide. An inhibitory monoclonal antibody specific for ras p21 amino acids 60-77 (Y13-259) had no effect on cell-free NADPH oxidase activation. Activation of the NADPH oxidase in intact neutrophils by stimulation with phorbol myristate acetate caused a marked increase in the amount of membrane-associated antigen recognized by 151 antiserum on Western blot. Thus a G protein in the cytosol of unstimulated neutrophils antigenically and functionally related to Krev-1 may be the downstream effector G protein for NADPH oxidase activation. This system represents a unique model to study molecular interactions of a ras-like G protein. PMID- 1906889 TI - Denaturation of proteins during heat shock. In vivo recovery of solubility and activity of reporter enzymes. AB - Using beta-galactosidase and luciferase as reporter enzymes, we have previously shown that enzymatic inactivation occurring during a heat shock is concomitant with protein insolubilization (Nguyen, V. T., Morange, M., and Bensaude, O. (1989) J. Biol. Chem. 264, 10487-10492). In this paper, we observe that pretreatment of cells with D2O and glycerol, compounds known to stabilize protein structure, leads to a parallel decrease of protein inactivation and insolubilization, suggesting that these two phenomena result most probably from heat-induced protein denaturation. We found that heat shock-promoted inactivation and insolubilization are not irreversible processes, since even in the absence of protein synthesis, beta-galactosidase solubility and luciferase solubility and activity are recovered in vivo after a heat treatment. Cognate heat shock proteins might be involved in this renaturation process. PMID- 1906891 TI - Interleukin-1 alpha stimulates prostaglandin biosynthesis in serum-activated mesangial cells by induction of a non-pancreatic (type II) phospholipase A2. AB - Enhanced prostaglandin (PG) biosynthesis is a hallmark of inflammation, and interleukin-1 (IL), a proinflammatory cytokine, is a potent stimulus of PG production. We investigated the mechanisms of IL-1 alpha-enhanced PG synthesis in serum-stimulated mesangial cells. The rIL-1-stimulated increase in PGE2 synthesis was dose- and time-dependent and inhibited by both cycloheximide and actinomycin D. Phospholipase (PL) activity was increased 5- to 10-fold in acid extracts of rIL-1-treated cells as measured by arachidonate release from exogenous [14C]arachidonyl-phosphatidyl-ethanolamine. This induced phospholipase activity was Ca(2+)-dependent and inhibited by the PLA2 inhibitors, aristocholic acid, 7,7 dimethyl-5,8-eicosadienoic acid, and p-bromophenacylbromide, but not by the 1,2 diacylglycerol lipase inhibitor RHC 80267. The rIL-1-stimulated PLA2 had an alkaline pH optimum, and phosphatidylethanolamine was preferred over phosphatidylcholine as substrate. The PLA2 activity increased by rIL-1 was inhibited in cells coincubated with cycloheximide and was measurable after 6 h. A sensitive and specific solution hybridization assay demonstrated a coordinate time-dependent induction of non-pancreatic PLA2 mRNA expression which was increased at least 6-fold by 24 h. In whole cells, IL-1 had no effect on basal [3H]arachidonic acid release but vasopressin (1 microM)-stimulated release was potentiated 2- to 3-fold, suggesting that IL-1 may prime cells for increased PG synthesis via increased PLA2 activity. Thus IL-1 directly stimulates, as well as primes cells for, enhanced PG synthesis, in part, by increasing PLA2 activity through new synthesis of a non-pancreatic (Type II) PLA2. PMID- 1906892 TI - Nucleotide deletion resulting in frameshift as a possible cause of complete thyroxine-binding globulin deficiency in six Japanese families. AB - Complete T4-binding globulin deficiency (TBG-CD) is inherited in an X-linked fashion. A nucleotide substitution has been shown to cause this hereditary condition in caucasians of French Canadian origin. Heterogeneity in molecular mechanisms for TBG-CD has also been reported. Genomic DNA from a Japanese male exhibiting TBG-CD was subjected to polymerase chain reaction, and the generated DNA fragments were sequenced. A single nucleotide deletion was found in the first base of the codon for amino acid 352 of the common-type TBG molecule. This mutation causes a frameshift in translation and premature termination. Compared with common-type TBG, the mutated polypeptide results in 1) 22 different amino acids on its carboxy-terminus, 2) a 22-amino acid truncation, and 3) the absence of a potential N-linked glycosylation site. These alterations may lead to profound changes in the secondary and tertiary structures of the molecule. To ascertain the presence of this nucleotide deletion in the genomic DNA of affected subjects, a mutated primer was designed which together with the nucleotide deletion produced a new endonuclease restriction site in the polymerase chain reaction fragment. Results revealed the presence of the mutation in genomic DNA of the subject, and his mother was shown to have both mutant and normal alleles. The same mutation was also detected in five other unrelated families carrying TBG CD. This mutation may be frequent in Japanese subjects with TBG-CD. PMID- 1906893 TI - Comparison of transdermal to oral estradiol administration on hormonal and hepatic parameters in women with premature ovarian failure. AB - Five women with premature ovarian failure were studied in a randomized cross-over design to compare the biochemical effects of transdermal to oral estradiol administration when used in doses appropriate for endometrial preparation in a donor oocyte program. Patients randomly received increasing dosages of oral micronized or transdermal estradiol for 4 week, with progesterone added in the last 2 weeks, to mimic a normal hormonal cycle. Serum samples were assayed throughout treatment and compared to those from normally cycling premenopausal controls. In general, serum estradiol remained within the normal range in both treatment groups, whereas peak serum estrone levels were 10-fold higher in the orally treated group than those in the transdermally treated group. Serum levels of sex hormone-binding globulin, thyroid binding globulin, and renin substrate were all significantly elevated by day 14 in the orally treated patients and unchanged in the transdermal subjects. While plasminogen was unaltered by either route of administration, antithrombin-III levels fell with both treatments. Changes in gonadotropin levels were similar in both groups, with suppression of FSH by the end of the simulated cycles, but not into the normal premenopausal range. In conclusion, both estrogen replacement regimens provided near-normal serum estradiol profiles. However, despite the relatively high doses necessary to mimic a hormonally normal cycle, the transdermal route did not significantly alter the hepatic parameters studied, suggesting that this route of administration may have less adverse hepatic effects. PMID- 1906894 TI - Increased induction of HLA-DR by interferon-gamma in cultured fibroblasts derived from patients with Graves' ophthalmopathy and pretibial dermopathy. AB - We investigated the effects of several cytokines on HLA-DR expression in cultured fibroblasts derived from retroocular connective tissue and pretibial and abdominal skin of patients with Graves' ophthalmopathy (GO) and pretibial dermopathy (PTD), as well as from normal individuals. We hypothesized that differences in response to cytokines between fibroblasts from various anatomical areas might play a role in the site-selective involvement of the extrathyroidal manifestations of Graves' disease. HLA-DR expression in fibroblasts was quantitated by scanning densitometry of whole cell lysates subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting. Direct immunofluorescence of cell monolayers was also performed. We hypothesize that unique characteristics of these fibroblasts may play a role in GO and PTD. Cultured retroocular, pretibial, and abdominal fibroblasts from patients with Graves' disease as well as from normal individuals did not express HLA-DR spontaneously. Treatment in vitro with interferon-gamma (IFN gamma; 100 U/mL) for 5 days induced HLA-DR by 50- to 80-fold (P less than 0.0001) in fibroblasts from all sites and subjects studied. However, IFN gamma-induced HLA-DR expression was significantly greater in retroocular (P less than 0.005) and pretibial (P less than 0.0005) fibroblasts from patients with GO and PTD than in fibroblasts obtained from the same anatomical sites of normal individuals. Further, retroocular and pretibial fibroblasts from patients with GO and PTD responded to IFN gamma more vigorously than did abdominal fibroblasts from these same patients (P less than 0.0001). IFN gamma-induced HLA-DR expression was enhanced by concomitant treatment with tumor necrosis factor-alpha (100 U/mL). In contrast, treatment of retroocular fibroblasts with transforming growth factor-beta (10 ng/mL), epidermal growth factor (1 ng/mL), or interleukin-6 (IL-6; 100 U/mL) significantly attenuated IFN gamma-induced HLA-DR reactivity by 40-59% (P less than 0.05). Incubation of retroocular fibroblasts with tumor necrosis factor alpha, IL-1 alpha (10 U/mL), IL-2 (10 U/mL), IL-6, granulocyte-macrophage colony stimulating factor (100 U/mL), epidermal growth factor, and transforming growth factor-beta alone did not affect HLA-DR expression. These results indicate that several cytokines can influence HLA-DR expression in cultured fibroblasts. The enhanced induction of HLA-DR by IFN gamma in retroocular and pretibial fibroblasts compared with that in abdominal fibroblasts may partially explain the selective involvement of the retroocular connective tissue and pretibial skin in fully expressed Graves disease. PMID- 1906895 TI - Hormone-responsive adenylyl cyclase in the human fallopian tube. AB - Hormone-responsive adenylyl cyclase (AC) activity in biopsies from normal human Fallopian tubes was studied. Enzyme activity with a Km of 0.15 mmol/L and a maximum velocity of 13.8 pmol/mg.min in the basal condition was demonstrated. The addition of prostaglandin E1 (PGE1), PGE2, PGF2a, vasoactive intestinal polypeptide, isoproterenol, and terbutaline increased enzyme activity, with no change in the Km. Maximum stimulation of AC activity was obtained with PGE1, resulting in a 2- to 8-fold increase in AC activity. The response of AC to PGE1 revealed a possible topographical variation, with lowest responses to PGE1 in the isthmus. No such segmental variation in AC activity and response was seen after stimulation with PGF2a, vasoactive intestinal polypeptide, or isoproterenol. PMID- 1906896 TI - Evidence for existence of immunoglobulins that block ovarian granulosa cell growth in vitro. A putative role in resistant ovary syndrome? AB - The sera of 26 patients with premature ovarian failure were examined in order to detect immunoglobulin-G (IgGs) that can block FSH-induced in vitro granulosa cell DNA synthesis via, a Feulgen cytochemical bioassay system. The IgGs of four patients with polycystic ovary-like disease, five postmenopausal women, and four eumenorrheic women served as controls. Ovarian growth blocking IgGs were found in 21 of the 26 premature ovarian failure (POF) cases. The few cases characterized by the absence of follicles (streak ovaries) and the controls were negative. The ovarian blocking IgGs were far more prevalent in the POF cases than anti cytoplasmic ovarian antibodies detected by an indirect immunofluorescence assay (only one of the 26 POF patients was positive). Our data hence confirm earlier expressed views that immune mechanisms are involved in a high proportion of patients with POF. PMID- 1906897 TI - Pregnancy in patients with mild thyroid abnormalities: maternal and neonatal repercussions. AB - A prospective study was undertaken during pregnancy in 120 euthyroid women presenting with mild thyroid abnormalities (TA): 11 with a past history of thyroid disorder, 44 with goiter, 20 with nodules, and 45 with thyroid autoantibodies. The aims of the study were to assess whether the pattern of thyroid alterations during gestation was different in women with TA compared to that in healthy control pregnant subjects and to evaluate possible obstetrical and neonatal repercussions. The overall prevalence of underlying subtle thyroid abnormalities in the cohort was 17%, probably as the result of the environmental moderately low iodine intake. Despite the intrinsic heterogeneity of the four groups of women with TA, the adaptation of the thyroid to the stress of pregnancy was different from that of the control subjects. Noteworthy were 1) the marked elevation of serum thyroglobulin in women with past history of thyroid disorder, goiter and thyroid nodules; 2) the increase in goiter size in a third of the goitrous women, associated with biochemical evidence of functional stimulation of the gland; 3) the indirect evidence of partial thyroidal autonomy in goitrous patients; and 4) the increase in the number and size of thyroid nodules during gestation. Taken together, the data indicated that pregnancy was associated with a greater thyroidal risk in patients with TA compared to healthy subjects. In relation to thyroid autoimmunity, most patients remained euthyroid during gestation, but in a few cases, TSH was elevated at delivery, suggesting diminished thyroidal reserve. Also, 40% of newborns from mothers with thyroid autoimmunity had elevated thyroid peroxidase antibody titers at birth, and there was a highly significant correlation between maternal and neonatal thyroid peroxidase antibody titers. Finally, thyroid autoimmunity was clearly associated with an increased risk of spontaneous abortion (13.3 vs. 3.3%; P less than 0.001). Thyroid function in newborns from mothers with TA was normal and not different from that in controls; similarly, obstetrical features were similar in patients with TA and control subjects. In conclusion, pregnancy is associated with a greater thyroidal risk in women with TA, thereby emphasizing a potential link between pregnancy and thyroid disorders. It is recommended that patients with known, even subtle, thyroid abnormalities be closely monitored during pregnancy, in particular those with a goiter, nodules, or thyroid autoimmunity, especially in areas with a moderately low iodine intake, where the prevalence of mild thyroid disturbances is high. PMID- 1906898 TI - Enterococcal meningitis in an HIV positive haemophilic patient. AB - A 25 year old, human immunodeficiency virus (HIV) seropositive, severe haemophilic patient was treated for suspected Pneumocystis carinii infection with high dose intravenous cotrimoxazole and subsequently with prednisolone. When he improved he was discharged on oral treatment only to return two days later, extremely unwell, with headaches, fever, sweats, tachycardia and hypotension. A lumbar puncture showed modest neutrophil pleocytosis but despite empirical antibiotic treatment with intravenous benzylpenicillin and cefuroxime he continued to deteriorate. Culture of cerebrospinal fluid subsequently grew Enterococcus faecalis that was resistant to trimethoprim and sensitive to ampicillin, rifampicin, and vancomycin. After a change in treatment to intravenous ampicillin and rifampicin he dramatically improved. Enterococcal meningitis is rare in adults but important to recognise and treat appropriately in view of its high mortality and relative resistance to antibiotics. In our case the combination of HIV infection and previous treatment with antibiotics or steroids, or both, were probable predisposing factors. PMID- 1906899 TI - Is managed care the future dental care delivery system? PMID- 1906900 TI - Organized dentistry's role in cost containment. PMID- 1906901 TI - [The effect of a cationic surface-active substance (catamine AB) on the physiological-morphological properties of B. cereus and E. coli]. AB - Catamine AB (0.05-0.5%) promotes transfer of B. cereus st 96, and E. coli st. 906 cell cultures into metabolic rest. Detergent-treated cells have no energetic metabolism and autolytic processes, have high light-scattering coefficient, and peculiar ultrastructural organization. Viable cells can be observed in the detergent-treated cell suspension after 1 year of incubation. Difference in action of different catamine AB concentrations on stationary and exponential B. cereus cells has been revealed. PMID- 1906902 TI - Proarrhythmia, cardiac arrest and death in young patients receiving encainide and flecainide. The Pediatric Electrophysiology Group. AB - The potential for proarrhythmic responses to the class IC sodium channel-blocking drugs encainide and flecainide has not been well described in young patients. Therefore, data were retrospectively collected from 36 institutions regarding 579 young patients who were administered encainide or flecainide for treatment of supraventricular tachycardias (encainide 86 patients, flecainide 369 patients) or ventricular arrhythmias (encainide 21 patients, flecainide 103 patients) to assess the frequency of proarrhythmia, cardiac arrest and death during therapy (adverse events). The two drugs were similar in regard to efficacy (flecainide 71.4%, encainide 59.8%) and rate of proarrhythmic responses (flecainide 7.4%; encainide 7.5%). However, patients receiving encainide more frequently experienced cardiac arrest (encainide 7.5% vs. flecainide 2.3%, p less than 0.05) or died during treatment (encainide 7.5% vs. flecainide 2.1%, p less than 0.05). Detailed data were provided for 44 patients experiencing one or more adverse events. Patient age, previous drug trials, concomitant therapy and days of inpatient monitoring were similar for patients receiving encainide or flecainide. However, echocardiographic left ventricular shortening before treatment was lower among patients receiving encainide (0.23 +/- 0.09) than among those receiving flecainide (0.34 +/- 0.06, p less than 0.05). Plasma drug concentrations were rarely elevated. Cardiac arrest (12 patients) and deaths (13 patients) occurred predominantly among patients with underlying heart disease, particularly among patients receiving flecainide for supraventricular tachycardia (8.3% vs. 0.3%, p less than 0.001). Fifteen patients with an ostensibly normal heart and normal ventricular function experienced proarrhythmia during treatment for supraventricular tachycardia, but only 3 of the 15 had a cardiac arrest or died. The relatively high incidence of adverse events should be considered when contemplating treatment with encainide or flecainide, particularly among patients with underlying heart disease. PMID- 1906903 TI - Encainide and flecainide in children: separating the wheat from the chaff. PMID- 1906904 TI - Depression of factor XII-dependent fibrinolytic activity characterizes patients with early myocardial reinfarction after recombinant tissue-type plasminogen activator therapy. AB - Twenty patients with acute myocardial infarction treated with recombinant tissue type plasminogen activator (rt-PA) had endogenous factor XII-dependent fibrinolytic activity levels measured throughout the hospital period and those levels were prospectively correlated with the incidence of recurrent myocardial infarction until 8 weeks after hospital discharge. Within the follow-up period, recurrent myocardial infarction was observed in 8 patients, whereas the remaining 12 patients showed no clinical evidence of recurrence. The patients in the reinfarction group were characterized by a more pronounced depletion of and sustained lower levels of factor XII-dependent fibrinolytic activity than were the patients with no reinfarction (p less than 0.05). The decrease in fibrinolytic activity during rt-PA therapy was significantly associated with a depletion of functional alpha 2-antiplasmin, the primary plasmin inhibitor. These results indicate that, paradoxically, coronary thrombolysis with rt-PA involves depletion of endogenous factor XII-dependent fibrinolytic activity levels, which constitutes a risk for early myocardial reinfarction. PMID- 1906905 TI - Alleviation of cocaine-induced coronary vasoconstriction by nitroglycerin. AB - Cocaine induces vasoconstriction of epicardial coronary arteries in patients with and without coronary artery disease, and this vasoconstriction is particularly marked in segments narrowed by atherosclerosis. To assess the effect of nitroglycerin on cocaine-induced coronary vasoconstriction, computer-assisted quantitative analysis was performed on non-diseased and diseased coronary artery segments in 23 patients (18 men, 5 women, aged 43 to 65 years) 1) at baseline, 2) after administration of intranasal saline solution (in 8 patients) or 2 mg/kg of cocaine (in 15 patients), and then 3) after administration of sublingual placebo (in 6 patients) or 0.4 or 0.8 mg of nitroglycerin (in 9 patients) in the 15 patients given cocaine. In response to cocaine administration, coronary artery cross-sectional area decreased 22 +/- 7% (mean +/- SD) in non-diseased segments (p less than 0.05) and 45 +/- 18% in diseased segments (p less than 0.02). The magnitude of vasoconstriction was greater (p = 0.01) in the diseased segments. Sublingual nitroglycerin abolished the vasoconstriction in both non-diseased and diseased segments. Thus, nitroglycerin alleviates cocaine-induced vasoconstriction in patients with coronary artery disease. PMID- 1906906 TI - Retrograde coronary venous administration of recombinant tissue-type plasminogen activator: a unique and effective approach to coronary artery thrombolysis. AB - Recent studies of interventional therapy by way of the coronary venous system have demonstrated that it can protect acutely ischemic myocardium. To evaluate the efficacy of coronary venous retroinfusion compared with systemic intravenous administration of recombinant tissue-type plasminogen activator (rt-PA), 14 dogs were studied with a copper coil-induced thrombus in the left anterior descending coronary artery. The rt-PA (24,000 fluorescence units/kg) was administered continuously, either intravenously (n = 8) or retrogradely (n = 6), for 30 min beginning 60 min after coronary occlusion. Thrombolysis was determined by repetitive coronary angiography. All dogs were killed 3 h after termination of rt PA infusion and infarct size was measured by the triphenyltetrazolium chloride staining technique. Complete thrombolysis occurred in five of the six dogs in the retroinfusion group and four of the eight dogs in the systemic intravenous infusion group. Partial lysis was achieved in two dogs treated by intravenous infusion. Lysis did not occur in one dog treated with retroinfusion and in two dogs treated with intravenous infusion. Time to thrombolysis was 13.4 +/- 2.3 min in the retroinfusion group versus 27.8 +/- 4.8 min in the intravenous group (p less than 0.001). Myocardial functional recovery in the ischemic zone measured by two-dimensional echocardiography 60 min after reperfusion was significant only in the retroinfusion group (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1906907 TI - The effects of ammonium sulphate and urea upon egg hatching and miracidial survival of Schistosoma mansoni. AB - The effects of various concentrations of ammonium sulphate and urea on egg hatching and miracidial survival of S. mansoni were tested in order to determine if the use of these fertilizers in the ricelands of the Republic of Cameroon could affect the transmission of schistosomiasis. Results indicate that hatching of eggs and survival of miracidia varied with concentrations of tested chemicals and times of exposure. Exposure of S. mansoni eggs to 0.20%-1.00% ammonium sulphate or to 0.50%-4.00% urea reduced their ability to hatch and produce miracidia. A chemical concentration of 1.00% ammonium sulphate or 4.00% urea was found to be sufficient to produce complete inhibition of hatching. High concentrations of both chemicals not only inhibited miracidial emergence but also may be ovocidal. Results obtained from miracidial survival tests indicated that LC5, LC50 and LC95 values for ammonium sulphate were 0.07%, 0.80% and 10.61% after 2 hours of exposure; 0.03%, 0.16% and 0.90% after 4 hours of exposure; and 0.30%, 0.20% and 0.40% after 6 hours of exposure respectively. Similar statistical analyses revealed that the LC5, LC50 and LC95 values for urea were 0.22%, 1.90% and 16.25% after 2 hours of exposure; 0.28%, 0.57% and 1.14% after 4 hours of exposure; and 0.13%, 0.27% and 0.57% after 6 hours of exposure respectively. Although the two fertilizers exerted some adverse effects on S. mansoni eggs and miracidia at relatively high concentrations, neither of them was found to be of practical value. Ammonium sulphate and urea concentrations effective in killing S. mansoni eggs and miracidia were about one to two orders of magnitude greater than the actual field application rates. PMID- 1906908 TI - Simultaneous visualization of LDL receptor distribution and clathrin lattices on membranes torn from the upper surface of cultured cells. AB - We have developed a method for simultaneous visualization by electron microscopy of both the distribution of cell surface receptors and architectural features of the inner membrane surface, such as clathrin-coated pits. Electron microscope grids were covered with formvar and coated with poly-L-lysine. These grids were then placed on a piece of buffer-impregnated cellulose acetate membrane filter maintained at 4 degrees C on an ice bath. Cells of interest were grown on glass coverslips and incubated with either a ligand-gold or an antibody-gold conjugate specific for the membrane determinant of interest. The coverslip with gold labeled cells was then overlaid on the grids and pressure was applied. When the grid was removed, large areas of the upper cell surface, which had labeled determinants, remained adherent to the formvar support. With the proper staining, both the gold particles and internal membrane features could be seen at the same time in the electron microscope. This method is rapid, does not require extensive experience with electron microscopic technique, and permits viewing of membrane samples that are large enough to perform quantitative analysis of gold distribution in relation to membrane specializations. PMID- 1906909 TI - A tetramethylbenzidine/tungstate reaction for horseradish peroxidase histochemistry. AB - Tracing of neuroanatomical pathways commonly involves the histochemical demonstration of horseradish peroxidase, using the chromogen tetramethylbenzidine. A new modification of this reaction using ammonium paratungstate stabilizer retains high sensitivity while permitting the reaction to be performed at pH 6.0 in isotonic solutions. The reaction product resists solvents, allowing Nissl-stained sections to retain their peroxidase labeling. With subsequent stabilization by diaminobenzidine, the tissue is suitable for electron microscopic study and is compatible with post-embedding immunocytochemistry. PMID- 1906910 TI - Meningococcal disease in the United States--1986. Meningococcal Disease Study Group. AB - Active surveillance for invasive meningococcal disease was conducted during 1986 and 1987 in six areas of the United States with a total population of approximately 34 million persons. The incidence of meningococcal disease was 1.3:10(5). The highest incidence of disease among the surveillance areas was in Los Angeles County (1.65:10(5). Neisseria meningitidis serogroups B and C caused about equal amounts of disease, which reflects a recent increase in the incidence of group C disease. Group C caused more than half of the cases of meningococcal disease in Los Angeles and Tennessee but less than one-third of the cases in Missouri and Oklahoma. Multilocus enzyme electrophoresis demonstrated that a group of closely related isolates of N. meningitidis was prevalent in Los Angeles during the surveillance period and was associated with an increased incidence of meningococcal disease there. PMID- 1906911 TI - Variation in class 5 protein expression by serogroup A meningococci during a meningitis epidemic. AB - Serogroup A meningococci were isolated from patients and healthy carriers in The Gambia between 1982 and 1988. The class 5 proteins expressed by these bacteria were identified by electrophoretic migration and by serologic tests. Three protein serologic groupings (seroclasses) called A (protein 5a), B (proteins 5b, 5d, or 5e), and C (protein 5c or 5C) were found among 331 bacterial isolates. The number of class 5 proteins expressed per isolate varied from none to four, with a median of two. The class 5 protein composition differed for certain paired isolates obtained from the nasopharynx, blood, and cerebrospinal fluid of diseased patients and for certain pairs of sequential isolates from the nasopharynx of healthy carriers; the medical relevance of this variation remains unclear, although the 5C protein was preferentially isolated from the nasopharynx and the 5a protein from diseased patients. The data show that a large proportion of healthy carriers in The Gambia were exposed to bacteria expressing each of the three seroclasses and that many people were exposed to bacteria expressing each of the three seroclasses and that many people were exposed to two or all three seroclasses during the epidemic of 1982-1983. PMID- 1906912 TI - Plasma neutrophil-activating peptide-1/interleukin-8 and neutrophil elastase in a primate bacteremia model. AB - A hyperdynamic sepsis model was set up in seven adult baboons to evaluate neutrophil-activating peptide-1/interleukin (IL)-8 (NAP-1/IL-8), IL-1 beta, IL-6, tumor necrosis factor-alpha (TNF alpha), and IFN-gamma in plasma. By continuous intravenous administration of 10(10) cfu/kg live Escherichia coli over 8 h with additional infusion therapy (less than or equal to 50 ml/kg/h), endotoxin plasma levels of 2.7-22.3 ng/ml were observed. In plasma the kinetics of NAP-1/IL-8 and IL-6 were similar to those of IL-1 at the end of the experiment (8 h) (peak median values, 34, 4197, and 230 ng/ml, respectively). Differences were greatest for IL-6. Monocyte activation during sepsis was confirmed by elevated plasma neopterin levels (91-139 mumol/mmol of creatine). Granulocyte activation was evident from both incipient neutropenia and the massive release of neutrophil elastase into the plasma as measured by a new immunoassay (peak level, 374 ng/ml). Thus, in primate bacteremia, early TNF release is followed by a concomitant increase of NAP-1/IL-8 with plasma kinetics similar to those of IL-6 and IL-1 and accompanied by massive activation of neutrophils. PMID- 1906914 TI - Elevated levels of soluble CD8 and soluble CD25 in patients with human T cell leukemia virus type I-associated myelopathy and adult T cell leukemia. PMID- 1906913 TI - Effect of Candida albicans plus histamine on prostaglandin E2 production by peripheral blood mononuclear cells from healthy women and women with recurrent candidal vaginitis. AB - The in vitro production of prostaglandin E2 (PGE2) by peripheral blood mononuclear cells (PBMC) in response to viable Candida albicans, histamine, and C. albicans plus histamine was examined. With PBMC from 10 healthy women, C. albicans but not histamine induced PGE2 at a low level (100 pg/ml). However, C. albicans plus histamine acted synergistically to stimulate PGE2 production (448 pg/ml). PBMC from 8 of 10 women with recurrent candidal vaginitis also produced maximal levels of PGE2 in the presence of C. albicans plus histamine. Production of tumor necrosis factor by PBMC from patients and controls was unaffected by histamine in both the presence and absence of C. albicans. However, unlike the controls, PBMC from six of the patients who were atopic and from two nonatopic patients spontaneously released PGE2 in vitro. Addition of 4 or 10 units/ml interferon-gamma inhibited spontaneous and C. albicans-induced PGE2 production by PBMC. These data reinforce the evidence that immediate hypersensitivity responses may be involved in the etiology of recurrent candidal vaginitis. PMID- 1906915 TI - Evidence of a correlation between CA15.3 and prolactin serum levels after TRH administration in women with gross cystic breast disease. PMID- 1906916 TI - [Augmentative effect of sizofiran on the immune functions of regional lymph nodes in patients with cervical cancer]. AB - Twenty mg of sizofiran (Schizophyllum glucan: SPG) was i.m. administered one day prior to surgery, or the same dose was injected 8 days and one day before surgery to 40 patients with cervical cancer and 15 with a benign tumor. Frozen sections of fresh pelvic lymph nodes from these patients obtained during surgery were stained by the ABC (Avidin-biotin-peroxidase complex) method with several monoclonal antibodies to define the surface phenotype of mononuclear cells. SPG led to a great increase in the number of cells stained with interleukin-2 receptor (IL-2R) and Leu 3a antibodies, mainly in PC, but with only a slight increase in the number of cells stained with Leu 2a, 7, 11, and M3 antibodies. This augmenting effect was more prominent in patients receiving two SPG injects that in those with a benign tumor. These results suggest that stimulus with some antigen (cancer antigen in the present study) may be required to induce immuno augmentation by SPG which has no antigenicity. Interestingly, the above augmenting effects could be seen even in metastatic lymph nodes from advanced cervical cancer patients. SPG was thus revealed to be a potent biological response modifier leading to augmented helper T (Th) cell functions of pelvic lymph nodes in cervical cancer patients, among which an enhanced IL-2/IL-2R system was noted. PMID- 1906917 TI - Purine analogs as chemotherapeutic agents in leishmaniasis and American trypanosomiasis. AB - The metabolic pathways for purines in parasitic protozoans differ significantly from the corresponding pathways in human beings. Leishmania and Trypanosoma cruzi have particular enzymatic reactions that have relevance for chemotherapy. Certain purine analogs are metabolized by the parasites to nucleotides and aminated to the analogs of adenine nucleotides. These halt protein synthesis and cause the break-down of RNA. The most important purine analogs with respect to chemotherapeutic potential are the pyrazolo [3,4-D]-pyrimidines. The prototype, allopurinol, is nontoxic to human beings and is aminated to adenine nucleotide analogs by the organism. Studies in vitro and in vivo have demonstrated its antiparasitic action and led to its development as a chemotherapeutic agent for diseases caused by these organisms. Clinical investigations now have demonstrated the therapeutic efficacy of allopurinol in cutaneous leishmaniasis caused by Leishmania braziliensis and in chronic Chagas' Disease. PMID- 1906918 TI - Role of 5-lipoxygenase products of arachidonic acid in cell-to-cell interaction between macrophages and natural killer cells in rat spleen. AB - In the present study we performed experiments to reveal the role of 5 lipoxygenase products of arachidonic acid in cell-to-cell interaction between rat peritoneal macrophages and spleen natural killer (NK) cells. Peritoneal macrophages were found to significantly enhance NK cell activity. It was found that the enhancing activity of macrophages was significantly inhibited by the ingestion of highly purified eicosapentaenoic acid-ethyl ester (EPA-E). But direct cytotoxic action of macrophage on target cells (YAC-1) was unchanged by the ingestion of EPA-E. In addition, the depressed enhancing activity of EPA enriched macrophages (EPA macrophages) was partially, but significantly, restored by the addition of either 10(-10) M leukotriene B4 (LTB4) or 10(-12) M 5 hydroperoxyeicosatetraenoic acid (5-HPETE). The partial restoring effect of 10( 10) M LTB4 was further significantly enhanced by the addition of 5-HPETE. In contrast 5-hydroxyeicosatetraenoic acid (5-HETE) had no modulatory effect on the depressed activity of EPA macrophages. LTB4, 5-HPETE, and 5-HETE had no direct effect on NK cell activity itself. Significantly less amounts of LTB4 and 5-HETE were produced in EPA macrophages as compared with that in control macrophages. The present study indicates that macrophage modulatory action on NK cells can be partly mediated by LTB4 and 5-HPETE, which are produced in macrophages. PMID- 1906920 TI - Archaebacterial ether lipid diversity analyzed by supercritical fluid chromatography: integration with a bacterial lipid protocol. AB - A strategy has been developed for archaebacterial lipid analysis which provides three times the information to describe archaebacterial isolates and is compatible with simultaneous eubacterial/eukaryotic lipid analysis of environmental samples. Eubacterial and micro-eukaryotic biomass, community structure, and nutritional status have been routinely defined in environmental samples by lipid analysis. Lipid profiles are also useful in eubacterial identification and taxonomy. Polar lipid or whole cell ester-linked fatty acids are generally analyzed by gas chromatography-mass spectroscopy. Archaebacteria are characterized by their ether-linked membrane lipids. There is, however, less diversity in the side chains of archaebacterial membrane lipids as compared the eubacterial ester-linked membrane lipids. The information content of the archaebacterial lipid profile was increased by separately analyzing the polar lipid, glycolipid, and lipid-extracted residue fractions. Identification and quantification were performed by supercritical fluid chromatography. Results are presented for three species of methanogens and four thermoacidophile isolates, and compared with a literature review. PMID- 1906919 TI - High density lipoprotein subpopulations from galactosamine-treated rats and their transformation by lecithin:cholesterol acyltransferase. AB - It is known that an acute hepatotoxicity is produced in rats by intraperitoneal administration of galactosamine; a consequence of this treatment is a marked deficiency of lecithin:cholesterol acyltransferase (LCAT) activity in the plasma compartment. In this study high density lipoprotein (HDL) from galactosamine treated rats was isolated, resolved into subpopulations, and characterized. In contrast to HDL from control rats, which elutes from gel filtration columns as a single peak and has a diameter of 13.1 nm, HDL from the galactosamine-treated animals was found to elute in five major zones with diameters of 7.8-35 nm. Characterization of these subpopulations has revealed that the larger fractions are enriched in apolipoprotein E, phospholipid, and cholesterol, but contain little cholesteryl ester, while the smallest two fractions contain mainly apolipoprotein A-I, are enriched in phospholipid, and have 50-60% of their cholesterol in the ester form. Incubation of HDL from treated rats with a source of LCAT activity plus low and very low density lipoproteins caused transformation of these subpopulations into a species which, by size and composition, was essentially identical to control rat HDL. In addition, when the subpopulations were individually incubated with purified human lecithin:cholesterol acyltransferase and bovine serum albumin, there was a similar convergence toward a moderate particle size approximating control rat HDL. Cross-linking studies showed that incubation with LCAT activity reduced the heterogeneity of the treated rat HDL. We conclude that the galactosamine treatment induces a complex mixture of HDL that bears strong similarities to the small, apoA-I rich and large, apoE-rich particles seen in LCAT deficiency or secreted by hepatic cells in culture. Furthermore, these species appear to coalesce in the presence of the d greater than 1.21 g/ml fraction of control serum to yield a fairly homogeneous population that resembles control rat HDL in size, composition, and apoprotein content. PMID- 1906921 TI - Mutations in CD8 that affect interactions with HLA class I and monoclonal anti CD8 antibodies. AB - The T cell co-receptor, CD8, binds to the alpha 3 domain of HLA class I (Salter, R.D., R.J. Benjamin, P.K. Wesley, S.E. Buxton, T.P.J. Garrett, C. Clayberger, A.M. Krensky, A.M. Norman, D.R. Littman, and P. Parham. 1990. Nature [Lond.]. 345:41; Connolly, J.M., T.A. Potter, E.M. Wormstall, and T.H. Hansen. 1988. J. Exp. Med. 168:325; and Potter, T.A., T.V. Rajan, R.F. Dick II, and J.A. Bluestone. 1989. Nature [Lond.]. 337:73). To identify regions of CD8 that are important for binding to HLA class I, we performed a mutational analysis of the CD8 molecule in the immunoglobulin (Ig)-like variable domain. Our mutational analysis was based on our finding that using a cell-cell adhesion assay murine CD8 (Lyt-2) did not bind to human class I. Since the interaction of human CD8 with HLA class I is species specific, we substituted nonconservative amino acids from mouse CD8 and analyzed the ability of the mutated CD8 molecules expressed in COS 7 cells to bind HLA class I-bearing B lymphoblastoid cells, UC. Mutants with the greatest effect on binding were located in a portion of the molecule homologous to the first and second hypervariable regions of an antibody combining site. In addition, a panel of 12 anti-CD8 monoclonal antibodies were used to stain the 10 CD8 mutants, and amino acids that affected antibody binding were localized on the crystal structure of the Bence-Jones homodimer, REI. Support for an Ig-like structure of CD8 can be found in the pattern of substitutions affecting antibody binding. This work supports the similar tertiary structure of the CD8 alpha-terminal domain and an Ig variable domain. PMID- 1906923 TI - Professional liability costs in the eighties. PMID- 1906922 TI - Role of transferrin, transferrin receptors, and iron in macrophage listericidal activity. AB - It is not yet known what properties distinguish macrophages which can kill facultative intracellular bacteria, such as Listeria monocytogenes, from those which cannot. Listeria is an organism which requires iron for growth, yet macrophage listericidal mechanisms are also likely to be iron dependent. We show here that resident peritoneal macrophages and thioglycollate-elicited macrophages cannot kill listeria, but proteose peptone-elicited and FCS-elicited macrophages can. All these cell populations phagocytose listeria. Transferrin receptor expression is low on resident cells, intermediate on peptone- and FCS-elicited cells, and high on thioglycollate-elicited cells. Transferrin transports iron into cells via the transferrin receptor: thus, iron content of resident cells is low, of peptone- and FCS-elicited cells is intermediate, and of thioglycollate elicited cells is high. Moreover, antibody to transferrin, which prevents it binding its receptor, inhibits listericidal macrophages from killing this bacterium. Finally, nonlistericidal cells with high transferrin receptor expression and high intracellular iron become listericidal if they are incubated with apotransferrin, an iron-free ligand which prevents iron uptake by cells. These data suggest that macrophages must have enough available intracellular iron to support listericidal mechanisms, but too much iron favors growth of the bacterium, which no longer can be killed by the macrophage. PMID- 1906924 TI - The Coke factor. PMID- 1906925 TI - A localization index for distinction between extracellular and intracellular antigens of Mycobacterium tuberculosis. AB - A series of mycobacterial antigens were quantified by immunoelectrophoresis, enzyme-linked immunosorbent assays, or SDS-PAGE with immunoblotting using antisera against purified mycobacterial antigens. The antigens showed a characteristic distribution profile. Some had a marked quantitative dominance in the culture fluid while others had a marked dominance in sonicates of whole washed bacilli. The majority of the antigens tested could thus be located and grouped as either secreted or cytoplasmic in terms of a localization index (LI) which is described. A 5-week-old Mycobacterium tuberculosis culture fluid preparation with a low degree of lysis was valuable in the delineation of localization indexes. The various secreted antigens showed a great span in LI values, from 5 to 1000. This variation may express different degrees of secretion efficiency or differences in tendency to adhere to the bacterial surface. The identification of proteins as extracellular or cytosolic according to their LI values was in agreement for cultures of M. tuberculosis with a low degree of lysis and cultures of M. bovis BCG and M. bovis AN-5 with significant lysis of the bacterial cells. PMID- 1906927 TI - Genetic and biochemical characterization of Bacillus subtilis 168 mutants specifically blocked in the synthesis of the teichoic acid poly(3-O-beta-D glucopyranosyl-N-acetylgalactosamine 1-phosphate): gneA, a new locus, is associated with UDP-N-acetylglucosamine 4-epimerase activity. AB - The resistance spectrum to bacteriophage phi 3T of different Bacillus subtilis 168/W23 strains hybrid for wall teichoic acids suggested that poly(3-O-beta-D glucopyranosyl-N-acetylgalactosamine 1-phosphate), a so-called minor teichoic acid of strain 168, forms part of the receptor for this phage, and a serologically related group of phages. A representative sample of 25 mutants specifically resistant to phi 3T, obtained from a mutagenized culture by direct selection, were all found to have a greatly reduced galactosamine content. Relevant mutations in these strains were shown by PBS1 transduction and transformation to belong to two linkage groups; a minority, associated with an atypical colony morphology, were localized between sacA and purA, whereas the majority mapped between gtaB and tagB1 (formerly tag-1), a region containing all known genes involved in the synthesis of the major wall teichoic acid, poly(glycerol phosphate). The former mutations mapped in a new locus, gneA, characterized by a deficiency in UDP-N-acetylglucosamine 4-epimerase, while the latter ones, as well as the previously identified pha-3 (Estrela et al., 1986, Journal of General Microbiology 132, 411-415), map is a locus named gga. They are likely to affect membrane-bound enzymes involved in the synthesis of the galactosamine-containing teichoic acid. A possible biological role of this polymer is discussed. PMID- 1906926 TI - Genes concerned with synthesis of poly(glycerol phosphate), the essential teichoic acid in Bacillus subtilis strain 168, are organized in two divergent transcription units. AB - Insertional mutagenesis has revealed that a 22 kbp segment from the hisA region of the Bacillus subtilis 168 chromosome (310 degrees on the genetic map) contains at least six independent transcription units, all apparently devoted to production of cell envelope components. Genes concerned with synthesis of poly(glycerol phosphate), poly(groP), an essential cell wall polymer in B. subtilis 168, are organized in two divergently transcribed operons denoted tagABC and tagDEF. Nucleotide sequence analysis indicates that three of these six genes encode extremely basic polypeptides. The deduced products of the tagABC operon may be involved in poly(groP) assembly and export, whereas those of the tagDEF operon, which are very hydrophilic, are more likely to be implicated in poly(groP) precursor biosynthesis. The first gene of the tagDEF operon encodes glycerol-3-phosphate cytidylyltransferase (Pooley et al., 1991, Journal of General Microbiology 137, 921-928) and its deduced product has significant homology with cholinephosphate cytidylyltransferase from yeast. There is also substantial homology between the deduced products of tagB in the tagABC operon and tagF in the tagDEF operon. PMID- 1906928 TI - Genes involved in meso-diaminopimelate synthesis in Bacillus subtilis: identification of the gene encoding aspartokinase I. AB - Thermosensitive mutants of Bacillus subtilis deficient in peptidoglycan synthesis were screened for mutations in the meso-diaminopimelate (LD-A2pm) metabolic pathway. Mutations in two out of five relevant linkage groups, lssB and lssD, were shown to induce, at the restrictive temperature, a deficiency in LD-A2pm synthesis and accumulation of UDP-MurNAc-dipeptide. Group lssB is heterogeneous; it encompasses mutations that confer deficiency in the deacylation of N-acetyl-LL A2pm and accumulation of this precursor. Accordingly, these mutations are assigned to the previously identified locus dapE. Mutations in linkage group lssD entail a thermosensitive aspartokinase 1. Therefore, they are most likely to affect the structural gene of this enzyme, which we propose to designate dapG. Mutation pyc-1476, previously reported to affect the pyruvate carboxylase, was shown to confer a deficiency in aspartokinase 1, not in the carboxylase, and to belong to the dapG locus, dapG is closely linked to spoVF, the putative gene of dipicolinate synthase. In conclusion, mutations affecting only two out of eight steps known to be involved in LD-A2pm synthesis were uncovered in a large collection of thermosensitive mutants obtained by indirect selection. We propose that this surprisingly restricted distribution of the thermosensitive dap mutations isolated so far is due to the existence, in each step of the pathway, of isoenzymes encoded by separate genes. The biological role of different aspartokinases was investigated with mutants deficient in dapE and dapG genes. Growth characteristics of these mutants in the presence of various combinations of aspartate family amino acids allow a reassessment of a metabolic channel hypothesis, i.e. the proposed existence of multienzyme complexes, each specific for a given end product. PMID- 1906929 TI - Effect of respiratory syncytial virus infection on mice with protein malnutrition. AB - Respiratory syncytial virus (RSV) pulmonary infection was produced in BALB/c mice fed protein-deficient diets in an effort to understand the severity of viral pneumonia in infants in developing countries. As in previously published experiments with Sendai virus, animals on the deficient diet became clinically malnourished, and certain aspects of their cell-mediated immunity were altered. The course of RSV infection in protein-deprived mice was essentially identical to that in normally nourished animals. The titer of virus recovered from lung homogenates over time, as well as the histologic picture of bronchiolitis, were identical under all experimental conditions. This model, unlike that of Sendai virus infection, fails to demonstrate an effect of protein malnutrition on RSV infection. PMID- 1906930 TI - Dichotic listening failure in dysphoric neuropsychiatric patients who endorse multiple seizure-like symptoms. AB - In the present investigation, the dichotic word listening performance of a sample of 25 dysphoric neuropsychiatric patients who endorsed multiple partial seizure like symptoms was compared with that of matched samples of normal controls and patients with mood disorders who did not endorse multiple seizure-like symptoms. Eighty percent of the patients who endorsed multiple episodic phenomena failed the dichotic listening task, compared with 8% of normal controls and 28% of patients with typical mood disorders. After treatment with carbamazepine, a subsample of polysymptomatic patients manifested significantly fewer seizure-like symptoms. This clinical improvement was typically associated with markedly improved dichotic listening performance in most cases. The results are consistent with our previous hypothesis that "subclinical" electrophysiological dysfunction may severely disrupt the normal transmission and processing of auditory information. Because it is sensitive to this type of presumed cerebral dysfunction and relatively specific, impaired dichotic listening performance is likely to be a useful clinical marker for this complex neuropsychiatric syndrome. PMID- 1906931 TI - Mitochondrial encephalomyopathies: a correlation between neuropathological findings and defects in mitochondrial DNA. AB - Neuropathological studies were carried out in two patients with mitochondrial encephalomyopathies in whom the underlying lesions in muscle mitochondrial DNA (mtDNA) and respiratory enzyme complexes have been investigated. The first, a man with Kearns-Sayre syndrome, died at the age of 49 years. Autopsy showed an old parietal lobe infarct, diffuse spongiform leukoencephalopathy of cerebral and cerebellar white matter and mild spongiform change in deep grey matter and brainstem nuclei. Heteroplasmy of skeletal muscle mitochondrial DNA with a 3.5 kb mtDNA deletion in one of two mtDNA populations was found. The second case, a woman, suffering from myoclonic epilepsy, cerebellar ataxia, bilateral sensorineural deafness, several 'stroke-like' episodes died at age 52. At autopsy, an old infarct was seen in the L internal capsule. Severe loss of neurons and gliosis were found in the dentate nuclei, moderate changes in the red nuclei and inferior olivary nuclei and mild changes in the substantial nigra and locus coeruleus. In both patients, skeletal muscle biopsy showed numbers of ragged-red fibres and intramitochondrial paracrystalline inclusions at electron microscopy. A defect in the synthesis of the ND5 subunit of the respiratory complex I was suggested in the second patient in whom a diagnosis of MELAS was made. PMID- 1906932 TI - Hyperprolactinemia in multiple sclerosis. AB - In order to clarify endocrine abnormalities due to hypothalamic involvement in multiple sclerosis (MS), serum prolactin levels were measured in 27 patients with MS and 22 healthy subjects. The presence of hypothalamic lesions was also studied by magnetic resonance imaging (MRI). Serum prolactin levels were found to be significantly higher in MS patients than in healthy controls in both sexes. Although only one patient had galactorrhea, one-third of the MS patients had mild to moderate hyperprolactinemia, which was a 4-13-fold increase over the mean value of healthy subjects. The results of thyrotropin-releasing hormone, sulpiride, L-DOPA and bromocriptine loading tests suggested a hypothalamic dysfunction, rather than pituitary prolactinoma in MS patients. Four of eight patients with hyperprolactinema had diencephalic hypothalamic lesion(s) contiguous with the third ventricle on the brain MRI, while none of the normoprolactinemic patients had any lesions in the diencephalon. All relapsing remitting patients with hyperprolactinemia showed a rise in prolactin levels in the acute stage of the relapse and a decrease during the recovering stage and the following remission phase. Our findings suggest that latent hyperprolactinemia due to hypothalamic dysfunction occurs frequently in MS patients in relapse. The increase of serum prolactin is considered to be a sensitive indicator for hypothalamic lesions in MS. PMID- 1906933 TI - Stroke-like episodes in familial mitochondrial encephalomyopathy: clinical and biochemical aspects. AB - Acute episodes of focal neurological dysfunction are a well-recognized complication of the mitochondrial encephalomyopathies. Because of rapid remission, biochemical tests and other diagnostic procedures are mostly performed after the acute phase. We report the case of a patient suffering from mitochondrial disease manifesting primarily with seizures, progressive deafness and dementia, who experienced multiple stroke-like episodes. Other members of the family with evidence of mitochondrial dysfunction are presented briefly. EEG and biochemical findings in the acute stage are correlated with clinical symptoms, showing characteristics distinct from the chronic illness. The possible involvement of dietary factors in the provocation of stroke-like episodes is discussed and regulation of glucose intake suggested as a strategy in the prevention of stroke-like episodes. PMID- 1906934 TI - Modeling zidovudine therapy: a cost-effectiveness analysis. AB - Zidovudine (ZDV), the first FDA-approved therapy for HIV/AIDS, poses a dilemma to the policymaker. On the one hand, ZDV extends the life of HIV-infected persons, producing a clear benefit. On the other hand, some fear that prolonging the lives of infected individuals may contribute to the increased spread of the virus and to a steep rise in the overall costs of AIDS to society. To address this issue, we present a simple model of ZDV therapy against a backdrop of HIV transmission in a population of sexually active, gay men. We find no basis for the fear of dramatic increases in the incidence of AIDS or its associated costs among gay men due to widespread ZDV distribution. On the contrary, our analysis suggests that ZDV therapy is cost-effective, particularly when it is accompanied by modest efforts to promote behavior change and prevention. PMID- 1906935 TI - A double blind randomized parallel trial of intramuscular methotrexate and gold sodium thiomalate in early erosive rheumatoid arthritis. AB - In a double blind study 57 patients with active erosive rheumatoid arthritis without malalignment or deformities (median disease duration 13 months) were randomly treated with 50 mg gold sodium thiomalate (GSTM) or 15 mg methotrexate (MTX) intramuscularly for 6 months. In the GSTM group, 5/28 patients had to be withdrawn because of side effects; in 2/28 the dose was reduced. In the MTX group, 2/29 were withdrawn, one was lost to followup. The number of swollen joints improved by over 6 in 18/26 (MTX) and in 15/21 (GSTM). Five clinical variables and the sedimentation rate improved significantly in both groups without significant intergroup differences. The radiographs of hands, wrists and forefeet (32 joints evaluated according to Larsen) showed a radiological progression in 11/26 (MTX) and in 8/20 patients (GSTM); however, the deterioration of the mean Larsen index was not significant. While there was no significant difference in effectivity, tolerability was better in the MTX group. PMID- 1906936 TI - Effect of interferon-gamma on B lymphocytes of patients with systemic lupus erythematosus. AB - We studied the effect of interferon-gamma (IFN-gamma) on B cells in systemic lupus erythematosus (SLE). Low density B cells, which were fractionated on density gradients of Percoll, increased, and high density B cells decreased in number in SLE. Proliferative response of the high density B cells to interleukin 4 was reduced by IFN-gamma in normal controls, but not in SLE. IgG production of whole B cells induced by interleukin 2 or phytohemagglutinin induced T cell factors was enhanced by IFN-gamma in both normal controls and SLE in which activated B cells were thought to be increased in number. Therefore, IFN-gamma may be one of the factors which promote polyclonal B cell activation in SLE. PMID- 1906937 TI - A novel autoantibody reactive with a 48 kDa tRNA associated protein in patients with scleroderma. AB - We identify 4 patients with progressive systemic sclerosis (PSS) possessing a previously undescribed serum anti-tRNA Ab (anti-Wa antibody). These sera yielded identical precipitin lines under double immunodiffusion using calf thymus extract and supernatant of pig spleen homogenate as antigen sources. Furthermore, all 4 sera were found to react with a 48 kDa protein using immunoblotting. This protein was subsequently found to be associated with tRNA when immunoprecipitation was conducted. In a survey of autoimmune patients' sera, anti-Wa Ab was observed in 3% (4 of 130) of patients with PSS, but not in other systemic rheumatic diseases. None of the 4 patients with PSS with anti-Wa Ab had myositis except that one patient complained of mild myalgia. PMID- 1906938 TI - Intestinal mucosal permeability in inflammatory rheumatic diseases. I. Role of antiinflammatory drugs. AB - Using the 51Cr-EDTA resorption test, gut permeability was measured in 129 patients with inflammatory joint diseases and in 97 control patients (42 patients with no inflammatory rheumatic disorders taking antiinflammatory medication and 55 healthy controls). Thirty-two patients (30 arthritis and 2 control patients) taking nonsteroidal antiinflammatory drugs (NSAID) as well as corticosteroids were excluded from statistical analysis. The intake of NSAID significantly increased gut permeability in controls but not in the arthritis groups. The same applied to corticosteroid intake. This could be due to the restricted number of arthritis patients who had never taken antiinflammatory drugs or to a disease related increased permeability. There was no statistically significant difference in altered gut permeability between patients taking NSAID and patients taking corticosteroids. Our findings suggest that drug induced alteration of gut permeability may not only be accounted for by an inhibition of mucosal cyclooxygenase activity, but that other enzymatic pathways in the arachidonic cascade might be implicated. PMID- 1906939 TI - Intestinal mucosal permeability in inflammatory rheumatic diseases. II. Role of disease. AB - Gut permeability as measured by the 51Cr-EDTA resorption test was determined in 56 patients with rheumatoid arthritis (RA), 73 patients with spondyloarthropathies (SpA), 18 patients with inflammatory bowel disease (IBD) and 97 controls (42 patients with no inflammatory rheumatic diseases and 55 healthy controls). Gut permeability was found to be increased in the 3 patient groups, partially due to the intake of antiinflammatory drugs. When only patients not taking these drugs were considered, an increased gut permeability was found in patients with SpA and IBD. In patients with RA gut permeability could not be evaluated as they were all taking antiinflammatory medication. Ileocolonoscopy with biopsies of the gut was performed in 62 of the 73 patients with SpA and disclosed subclinical gut inflammation in 21. No difference in gut permeability was found between patients with or without gut inflammation. However, when the type of gut inflammation was considered, a significant increase of gut permeability was found in patients with chronic gut inflammation compared with patients presenting acute lesions. Our findings again suggest that the chronic gut inflammation seen in SpA is fundamentally different from acute gut inflammation and possibly related to the gut inflammation of IBD. PMID- 1906940 TI - Antigenicity and accessory cell function of human articular chondrocytes. AB - It is postulated that chondrocytes may be actively involved in the pathogenesis of inflammatory joint diseases, presumably by providing tissue specific antigens that may initiate or sustain autoimmune reactions. To investigate whether chondrocytes may also function as accessory cells in ongoing immune processes, mixed leukocyte-chondrocyte cultures and antigen presentation assays were studied. Freshly isolated and short term cultured HLA class II antigen (Ia) negative as well as gamma-interferon treated Ia positive chondrocytes were weakly or not stimulatory to allogeneic or autologous resting lymphocytes derived from either normal donors or patients with rheumatoid arthritis. In an antigen presenting system using tetanus toxoid, the majority of chondrocyte preparations tested induced an antigen driven response in HLA matched allogeneic or autologous resting T cells which, however, was much less when compared to blood monocytes. In contrast, using activated T cells derived from tetanus toxoid specific T cell lines, an efficient antigen presenting capacity could be demonstrated in both Ia positive and initially Ia negative chondrocytes. Interestingly, the latter population had acquired Ia antigens upon incubation with the T cell line. PMID- 1906941 TI - Regulation of the F plasmid traY promoter in Escherichia coli K12 as a function of sequence context. AB - TraJ and SfrA are, respectively, plasmid and host (Escherichia coli)-encoded proteins normally required for F plasmid traY promoter function. Beginning with plasmids in which a traY-lacZ fusion gene, designated phi (traY'-'lacZ)hyb, and lacY are expressed from the F plasmid traY promoter, we isolated mutants in which lac gene expression was SfrA or TraJ-independent. A total of 45 of 50 SfrA independent isolates obtained after 2-aminopurine mutagenesis proved to have chromosomal mutations, whereas four out of four isolates obtained without mutagenesis had plasmid mutations. All of 17 isolates selected for TraJ independent expression after mutagenesis had plasmid mutations. By restriction endonuclease digestions, 25 of 26 SfrA-independent and TraJ-independent plasmid mutations were insertions. Four of the former and three of the latter were examined further. By sequence analysis, all seven proved to be IS1 or IS2 insertions defining five insertion sites between base-pairs -49 and -82 with respect to the major traY transcription initiation site. In two cases, the same insertion allele was obtained from the two selection schemes. All three of the mutants selected for TraJ-independent gene expression manifested SfrA-independent expression as well, and levels of beta-galactosidase in different plasmid mutant strains lacking TraJ and SfrA were indistinguishable. By primer extension analysis, transcription initiation sites for traY mRNA synthesis were unaltered by the mutations. Replacing the tra sequence upstream from base-pair -78, without genetic selection, increased beta-galactosidase activity in the absence of TraJ and SfrA greater than tenfold. Activity increased two- to threefold more in a traJ+ sfrA mutant strain, and fivefold more in a traJ+ sfrA+ strain. Activity was unaltered in an sfrA+ strain without TraJ. By primer extension analysis, the traY promoter was utilized under all conditions. The data indicate that regulation of traY promoter activity is strongly dependent on sequence context. PMID- 1906942 TI - Neutron diffraction studies of the structure of filamentous bacteriophage Pf1. Demonstration that the coat protein consists of a pair of alpha-helices with an intervening, non-helical surface loop. AB - The structure of filamentous bacteriophage Pf1 has been studied using neutron diffraction from magnetically oriented gels of native and specifically deuterated phage. These methods have been used to determine the positions of the two methionine, two tyrosine and six isoleucine residues of the coat protein. Combined with the positions of the five valine residues previously determined, they represent one third (15 of 46) of the residues of the coat protein. These 15 amino acid residue positions have been used as the basis for constructing a model for the protein consisting of two alpha-helices with an intervening surface loop. The first helix extends from near the amino terminus to Ile12. The second helix extends from Lys20 to at least Met42, and may contain a bend between Ile32 and Val35. The two helices are tilted by about 15 degrees relative to one another, and are positioned in such a way that they appear to be bound end-to-end by main chain hydrogen bonds. The intervening, non-helical loop, made up of Thr13 to Met19, connects the two helices without disrupting the pattern of main-chain hydrogen bonding, but does not result in a bend in the otherwise continuous helical structure. This model is used to predict the approximate positions of all amino acid residues in the Pf1 protein coat, providing a basis for further understanding of a number of viral properties including the symmetry transitions, the non-isomorphism of heavy-atom derivatives, and the protein-protein and protein-DNA interactions in the virion. PMID- 1906943 TI - Inhibition of human fetal brain acetylcholinesterase: marker effect of neurotoxicity. AB - Human fetal brains were obtained after medical termination of pregnancy at 8-10 wk from informed patients. A definite regionalization of AChE was found in the brain of the fetus, with cerebellum recording the highest and cerebral hemisphere the lowest activity. Optimum conditions for the cerebellar AChE activity were determined with respect to molarity of the buffer, pH, temperature, and concentrations of substrate (acetylthiocholine iodide), activators (NaCl, MgCl2), and thiol indicator (dithiobisnitrobenzoic acid). In vitro inhibition of cerebellar AChE with two commercial pesticides, Metacid-50 (O,O-dimethyl p nitrophenyl phosphorothioate) and carbaryl (N-methyl naphthyl-1-carbamate), were compared with pure anticholinesterase agents, diisopropylfluorophosphate (DFP) and physostigmine (eserine). In general, organophosphates are more neurotoxic than carbamate compounds, as evidenced by higher degree of AChE inhibition by DFP and Metacid-50 as compared to eserine and carbaryl. Assays were also done with psychotropic drugs by employing the procedure of in vitro AChE inhibition kinetics, and it was found that psychotropic drugs are less potent than organophosphate and carbamate compounds. Results indicate that pure and commercial organophosphates and carbamates and psychotropic drugs are all able to significantly alter the AChE activity. Thus exposure of the mother to these environmental toxicants may adversely affect the fetal neural functions. PMID- 1906944 TI - Effect of nerve growth factor on C-1300 murine neuroblastoma tumor growth and catecholamine content in neonatally sympathectomized mice. AB - The in situ C-1300 murine neuroblastoma (MNB) tumor model was used to investigate the influence of exogenously administered nerve growth factor (NGF) on tumor growth and tissue catecholamine concentration in mice sympathectomized with 6 hydroxy-dopamine (6-OHDA) on postnatal days 4-10. Mice were implanted with 1 x 10(6) disaggregated MNB cells 3 days after termination of 6-OHDA administration. NGF (12-15 micrograms/mouse/day) treatment was initiated at the time of MNB cell implantation and continued until sacrifice of the animal. The time interval between tumor cell implantation and detection of palpable tumor (tumor onset time), transverse tumor diameter, tumor weight, tumor weight to body weight ratio, and tumor catecholamine concentration were determined. Neonatal sympathectomy caused a decrease in myocardial norepinephrine concentration of 88% compared with vehicle-treated animals as well as a significant reduction in total body and organ weight. Average body, brain, heart, and spleen weights were decreased 31%, 16%, 25%, and 42%, respectively, below control values. The daily injection of NGF, from the time of MNB tumor implantation to sacrifice, did not prevent these effects of chemical sympathectomy from being expressed. Tumor onset time following implantation of MNB cells was significantly increased in neonatally sympathectomized mice and was not altered by treatment with NGF. In contrast, the decrease in MNB tumor growth rate observed in sympathectomized mice was reversed by administration of NGF. Mean tumor weight and mean tumor to body weight ratio were 89% and 115% of comparable control values, respectively, in sympathectomized mice receiving exogenous NGF.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1906945 TI - Differential taurine uptake in central and peripheral regions of goldfish retina. AB - The transport system of taurine was investigated in fragments of goldfish retina prepared from the total tissue and from concentric regions: center and periphery. A high-affinity, saturable, sodium-dependent system was demonstrated in the three types of fragments. The Km for one-site analysis was similar in the two regions and the total retina. The analysis for two sites revealed a significant higher Km for the high-affinity site in fragments from the central region. The maximal uptake rate was higher in the central zone than in the total retina or the periphery. The Hill slopes obtained from saturation experiments of fragments of total retina, center, and periphery were similar to one other and near to 1. The slope of the time course uptake was intermediate for total retina and higher in the center than in the periphery. Hypotaurine and beta-alanine were found to inhibit taurine uptake, but GABA was a weak inhibitor. The values of Ki for hypotaurine by one- and two-site analysis were lower in the central region. The disruption of photoreceptors by shaking did not modify significantly the uptake of the amino acid. Remotion of endogenous taurine by dialysis of central and peripheral fragments increased the uptake in the periphery, but not in the center. The differences observed among the three samples revealed less affinity and high capacity for taurine uptake in the center, plus a higher sensitivity of inhibition. In addition, the peripheral zone had a greater affinity for taurine, and the maximal velocity of the entrance seems to be inhibited by the higher concentration of the amino acid in this zone. These observations may reflect differences between proliferating and non-proliferating regions of the retina (i.e., periphery and center). PMID- 1906946 TI - Adult paratesticular sarcomas: a review of 21 cases. AB - We reviewed 21 patients more than 16 years old who were seen with a diagnosis of paratesticular sarcoma from 1958 to 1987. Of the patients 14 presented with primary disease and 7 with recurrent disease. The survival of the primarily treated patients was 58% at 5 years, calculated by the product limit method. Of the 14 patients with primary disease 13 had grade 3/4 or 4/4 sarcoma and 13 of 14 underwent initial radical orchiectomy. In addition, 6 of the 14 patients underwent an adjuvant operation or radiotherapy to the groin, or groin and scrotum, and none had local relapse. Some patients also had chemotherapy. Three patients underwent adjuvant retroperitoneal node dissection and 2 had microscopically positive nodes. All 3 patients remain without relapse. Six patients had relapse: 2 locally, 2 in the retroperitoneal nodes and 2 with distant metastases. Only 1 patient (with scrotal recurrence) was salvaged. Of the 7 patients referred with recurrent disease none was salvaged. In this series there is a 2 of 14 (14%) risk of local failure and a 4 of 14 (28%) risk of retroperitoneal relapse after radical orchiectomy. Since salvage has not proved successful, patients with rhabdomyosarcoma, intermediate or high grade malignant fibrous histiocytoma, or fibrosarcoma should be considered for adjuvant retroperitoneal node dissection. All patients should undergo adjuvant dissection or irradiation of the ipsilateral pelvic and groin nodes, and scrotum. PMID- 1906947 TI - Guidelines for the scientific review of enteral food products for special medical purposes. Prepared for the Center for Food Safety and Applied Nutrition, Food and Drug Administration. PMID- 1906949 TI - [Post-transfusion viral hepatitis]. PMID- 1906948 TI - [Blood type incompatible in pregnancy secondary to blood transfusion]. PMID- 1906950 TI - [Blood groupings and antibody screening in Japanese Red Cross Blood Centers]. PMID- 1906951 TI - [Laboratory tests in Japanese Red Cross Blood Centers to prevent transfusion transmitted diseases]. PMID- 1906952 TI - [MSBOS and T & S--their significance and practice]. PMID- 1906953 TI - [Emergency blood transfusion and massive blood transfusion]. PMID- 1906954 TI - [A study on the mechanisms whereby apolipoprotein A-1 (apo A-1) inhibits cholesterol crystal nucleation in human gallbladder bile]. AB - The aim of the present study was to determine the mechanisms whereby apo A-1 retards cholesterol crystal nucleation in human gallbladder bile. Ten human gallbladder bile samples were sterilely collected from patients with gallstones at surgery, subsequently applied on gel permeation chromatography to separate various lipid particles. A non-micellar fraction coeluted with apo A-1 was ultrastructurally characterized by transmission electron microscopy (TEM). As results, that fraction containing very little or no apo A-1, 400-600 A in diameter, showed rapid transformation, i.e. rouleau formation, multilamellar formation and consequently microcrystal formation, whereas those rich in apo A-1, 200-400 A in diameter, showed very little transformation for 7 days. Those data indicated that apo A-1 stabilizes non micellar fraction by forming an apo A-1 and lipid complexed particle, resulting in prolonged cholesterol crystal nucleation. PMID- 1906955 TI - Bovine brain coated vesicles contain guanine nucleotide regulatory proteins. AB - Binding of [3H]guanosine triphosphate (GTP) with a high affinity was found to be present in the coated vesicle fraction prepared from bovine cerebral cortex. The binding was saturable and displaced by 1 microM of GTP, guanosine diphosphate and guanosine 5'-(3-O-thio)triphosphate. Incubation of the vesicles with islet activating protein and [32P]NAD resulted in ADP-ribosylation of a 39,000-41,000 dalton polypeptide. Antibodies to the alpha-subunit of stimulatory guanine nucleotide regulatory proteins (G-proteins) immunoblotted 52,000- and 45,000 dalton polypeptides. The results indicated that stimulatory and inhibitory G proteins are contained in a fraction of the bovine brain coated vesicles. PMID- 1906956 TI - The relationship between juxtapapillary duodenal diverticula and the presence of bacteria in the bile. AB - A total of 432 patients with gallstone disease were studied with respect to the existence of juxtapapillary duodenal diverticula and their relationship to the presence of bacteria in the bile. A total of 63 patients were found to have diverticula with an incidence of 14.6 per cent, being significantly higher in the elderly group aged 60 years or older (p less than 0.01), and no sex difference was noted. Among the patients with diverticula, positive bacterial cultures of bile were recognized at a significantly higher frequency, being found in 49 of the 63 patients (77.8 per cent; p less than 0.01), and the probability of bilirubinate stones was also higher, being found in 35 of 37 patients (94.6 per cent; p less than 0.01). The presence of a diverticulum bore significant relation to a higher positive bile bacterial culture (p less than 0.05), dilation of the common bile duct (p less than 0.05), and elevation of the bile duct pressure (p less than 0.05), even when the conditions were divided into cholecystolithiasis or choledocholithiasis. It was suggested that the presence of a diverticulum affected the flow in the bile duct by narrowing it from the outside and chronically stimulating the papilla, inducing biliary tract infection and/or the formation of gallstones. As the surgical procedures for juxtapapillary duodenal diverticula, including its indications, have not been established, long term follow up investigations seem necessary. PMID- 1906957 TI - The influence of stromal cells on the MTT assay (I)--In vitro chemosensitivity of the tumor and stromal cells to mitomycin C. AB - To clarify the influence of stromal cells on the 3-(4,5-dimethyl-2-thiazolyl)-2,5 diphenyl-2H tetrazolium bromide assay (MTT assay), a gastric carcinoma cell line (KATO-III) and a human fibroblast cell line (IMR-90) were subjected to a colorimetric assay, in which the chemosensitivity KATO-III was found to be highly sensitive to mitomycin C at 10 micrograms/ml, whereas IMR-90 was insensitive to mitomycin C at the same concentration. When the mixtures of these two cell lines were tested by the assay, a mixture of more than 25 per cent stromal cells reduced the sensitivity of KATO-III to mitomycin C. This suggested that the stromal cells in fresh surgical specimens might reduce the apparent sensitivity of the tumor cells. PMID- 1906958 TI - The influence of stromal cells on the MTT assay (II)--Study on the nude mouse system. AB - A fresh surgical specimen from colon carcinoma was tested by the 3-(4,5-dimethyl 2-thiazolyl)-2,5-diphenyl-2H tetrazolium bromide assay (MTT assay) and transplanted into nude mice. After 5 transfers in male BALB/c nude mice, the xenograft was then tested again by the MTT assay. It was found that the in vivo chemosensitivity pattern of the xenograft was essentially identical to that of the in vitro fresh surgical specimen, whereas the sensitivity of the xenograft was increased. To exclude the stromal cells from the nude mouse, anti-BALB/c serum was added to the primarily cultured colon carcinoma xenograft, and its chemosensitivity to mitomycin C (MMC) assessed. Although the sensitivity of the serum-treated group to MMC was slightly higher than that of the untreated group, the dose-response curves of the tumor cells to MMC were similar to each other. Thus, the chemosensitivity pattern of tumor cells seemed to be stable with or without normal cells, although the sensitivity itself was reduced by the presence of normal cells. PMID- 1906959 TI - [Effect of intravenous administration of aspisol on hemostasis and pain syndrome in patients with progressive angina]. PMID- 1906960 TI - [A case of Recklinghausen's disease]. PMID- 1906961 TI - Static and dynamic accuracy required of gas concentration measuring instruments. AB - The dynamic and static accuracy required of gas concentration measuring instruments for the measurement of physiological parameters is discussed. Static accuracy is examined using error sensitivity analysis of a range of physiological measurements requiring gas concentration information. From this an acceptable static accuracy of +/- 0.1 per cent volume/volume is established as an acceptable accuracy. Dynamic accuracy is examined using an idealised exhaled carbon dioxide curve. By considering the contribution of various features in the curve to the power spectrum of the curve a 'rule of thumb' for acceptable dynamic bandwidth of acceptable bandwidth = 4 (heart rate/60) + 5 Hz where heart rate is in beats min 1, is developed. PMID- 1906962 TI - A randomized, controlled trial of an attending staff service in general internal medicine. AB - This study, a prospective, randomized trial comparing two inpatient staffing models, was undertaken to compare clinical and financial outcomes for general medicine inpatients assigned to resident (teaching) or staff (nonteaching) service. Key outcome measures included: 1) length of stay; 2) total charges; 3) laboratory, radiology, pharmacy, and supplies charges; 4) in-hospital mortality and mortality within 6 months of admission; and 5) 15-day readmission rate. The study took place at Henry Ford Hospital, a 937-bed urban teaching hospital in Detroit, Michigan; the subjects included all general internal medicine patients admitted to a single nursing unit of Henry Ford Hospital between October 1, 1987 and September 30, 1988. When the unit was fully staffed and operational, patients admitted to the Staff Service had a 1.7-day lower average length of stay than patients admitted to the Resident Service (P greater than 0.005), lower average total charges of $1,681 (P greater than 0.01), and significantly lower laboratory and pharmacy charges. No statistically significant differences in mortality rates or readmission rates were found. Even though personnel costs are invariably higher on an attending service, this staffing arrangement can be financially viable because of more efficient patterns of care. Shorter length of stay may be translated either into cost savings or increased revenues in order to offset higher salary costs. Teaching hospitals may wish to consider an attending service as one way to reduce house officer work loads, offer more opportunities for training in ambulatory settings, and adjust to a smaller pool of applicants for residency positions. PMID- 1906963 TI - [A routine vocal cord examination in throat surgery is not justified]. PMID- 1906964 TI - [Ambulatory angiography saves money and shortens waiting time]. PMID- 1906965 TI - A model for asymmetric septum formation during sporulation in Bacillus subtilis. AB - Many differentiation processes in both prokaryotes and eukaryotes begin with an asymmetric division, producing 'daughter' cells that differ in size and developmental fate. This is particularly obvious in the well-studied prokaryotic life cycles of Caulobacter and Bacillus. In no system, however, is the mechanism of asymmetric division understood. Here I propose a model for the mechanism of asymmetric division during sporulation in Bacillus subtilis. The model explains both the timing and asymmetric localization of spore-septum formation. It also explains the morphological phenotypes of various asporogenous (spo) mutants. PMID- 1906966 TI - Origin of tetracycline efflux proteins: conclusions from nucleotide sequence analysis. AB - The sequences of six tetracycline efflux proteins and three transport proteins which have some resemblance to them were compared. The tetracycline efflux proteins fall into three families: (i) those encoded by pBR322, RP1, and Tn10 (Escherichia coli); (ii) pT181 (Staphylococcus aureus) and pTHT15 (Bacillus subtilis); and (iii) tet347 (Streptomyces rimosus). There is global sequence homology within each of the first two families, but there is none between the families. The pT181/pTHT15 family shares close homology with the N-terminal half of the methylenomycin A efflux protein (Streptomyces coelicor), while tet347 resembles the C-terminal half. Portions of the N-terminal half of the Tn10 encoded protein show significant resemblance to portions in the N-terminal half of the pT181/pTHT15 family, but this sometimes occurs among transport proteins which do not have a common substrate. Tetracycline efflux proteins, therefore, appear to have arisen on at least two, or possibly three, separate occasions, probably from other transport proteins. PMID- 1906967 TI - Regulation of the chlA locus of Escherichia coli K12: involvement of molybdenum cofactor. AB - The chlA locus encodes functions required for the biosynthesis of the molybdopterin part of the molybdenum cofactor. Mutants, carrying gene fusions at the chlA locus, which place beta-galactosidase expression under the control of the chlA promoter, have been isolated employing lambda placMu1 as the mutagen. The mutants exhibited beta-galactosidase expression which was greatly enhanced when grown anaerobically. Secondary mutations at the chlB, D, E or G loci did not affect the high level of expression. The fnr gene product was not required for the anaerobic expression. Bacteriophage lambda transducing phages were isolated which carried the phi(chlA-lac) mutations and were used to construct chlA+/phi(clA-lac) merodiploids. The merodiploids exhibited a much lower level of expression but showed the same characteristics as strains carrying lac fusions to the single chromosomal chlA locus. Genetic evidence is presented which strongly suggests that the molybdenum cofactor is a repressor of chlA expression. The anaerobic enhancement of chlA expression is mediated via a mechanism that is distinct from the molybdenum cofactor effect. PMID- 1906969 TI - Pleiotropic changes resulting from depletion of Era, an essential GTP-binding protein in Escherichia coli. AB - Phenotypic analysis of a temperature-sensitive era mutant strain indicates that Escherichia coli cells depleted of Era undergo many physiological changes. At 43 degrees C, a completely non-permissive temperature, growth is arrested because of loss of the gene and depletion of the Era protein. Depletion of Era at 43 degrees C results in depressed synthesis of heat-shock proteins DnaK, GroEL/ES, D33.4 and C62.5, lack of thermal induction of ppGpp pool levels, and increased capacity for carbon source metabolism through the citric acid cycle. Thus, in addition to inhibition of cell growth and viability, loss of Era function results in pleiotropic changes including abnormal adaptation to thermal stress. PMID- 1906970 TI - Replication mutants of Staphylococcus aureus macrolide-lincosamide-streptogramin B resistance plasmid pT48. AB - Copy-number mutants of Staphylococcus aureus macrolide-lincosamide-streptogramin B (MLS) resistance plasmid pT48 were isolated by their resistance to the non inducing macrolide, tylosin. One mutant plasmid, pcopD3, showed a three- to five fold cis-dominant increase in copy number, and nucleotide sequence analysis revealed that the mutant had a single base change within the replication region. All other pT48 mutants examined had the unusual phenotype of increased plasmid multimerization and elevated copy number. These mutants were effective in trans and DNA sequencing showed that plasmids with this phenotype were deleted in one of two ways. The deletions caused similar alterations to the C-terminus of the wild-type pT48 Rep protein. The two types of mutant Rep proteins terminate with the same pentapeptide sequence: Ala-Asn-Glu-Ile-Asp. The multimerization phenotype of these mutants can be explained by defective termination of rolling circle type replication. PMID- 1906968 TI - L-pilin variants of Neisseria gonorrhoeae MS11. AB - Phase- and antigenic variation of pilin expression in Neisseria gonorrhoeae is based on the genetic exchange between silent pilin genes (pilS) and the pilin expression locus (pilE). Similarly, the non-piliated L-variants of strain MS11, which show an increased resistance to certain antibiotics, are the result of recombination with the pilE locus. However, this recombination is atypical in that pilE(L) carries a tandem arrangement of a complete pilin gene and additional partial pilin genes under the control of the same pilE promoter. Since the two pilin gene copies are tandemly arranged and are often in the same translational frame, oversized pilin molecules are produced, which do not assemble into pili. The tandem gene copies introduced in a pilE(L) locus originate from silent loci where they are already joint. Upon reversion to the P+ phenotype the L-variants lose one pilin gene copy from the pilE(L) in a process reminiscent of the deletion events that otherwise lead to the formation of the non-revertible and non-piliated Pn mutants of MS11 gonococci. Thus deletion of pilin genes from pilE can be regarded as a third mechanism of pilin variation in gonococci. PMID- 1906972 TI - Identification and activation of latent transforming growth factor beta. PMID- 1906971 TI - Construction and expression of transforming gene resulting from fusion of basic fibroblast growth factor gene with signal peptide sequence. PMID- 1906973 TI - Increased poly(ADP-ribose)polymerase activity in cells infected by human immunodeficiency virus type-1. AB - Poly(ADP-ribose)polymerase is a chromatin-bound enzyme which is activated by free DNA ends and is therefore stimulated by a variety of DNA-damaging agents. The enzyme transfers the ADP moiety of NAD to nuclear proteins to create protein bound ADP-ribose polymers. Under conditions favouring an accelerated poly(ADP ribose) polymer formation, the enzyme may exhaust cellular NAD pools. At the same time, or shortly thereafter ATP levels drop and cell viability eventually declines. As a series of chemical and physical agents which may play a role in activating latent HIV-1 infection or favouring HIV-1 replication, have a DNA damaging activity, we investigated the behaviour of poly(ADP-ribose)polymerase activity in various types of HIV-1-infected cells. The results obtained show that HIV-1-infected cells to possess an increased poly(ADP-ribosol)ating activity together with an accentuated fragmentation of cellular DNA which are associated with the time course of HIV-1 replication. These data give circumstantial support to the hypothesis that a NAD-depdendent cellular suicide response to DNA damage, could play a role in the death of HIV-1 infected cells. In this respect, the impared immunocompetence of HIV-1-infected patients could bear some resemblance to immune attribution that sometimes accompanies some inborn errors affecting DNA precursor metabolism and DNA integrity. PMID- 1906974 TI - The safety and cost-effectiveness of low osmolar contrast media. PMID- 1906975 TI - Aflatoxin B1 alters central and systemic tryptophan and tyrosine metabolism: influence of immunomodulatory drugs. AB - Semi-chronic exposure of ICR male Mice to Aflatoxin B1 (AFB1) in non-toxic doses results in elevated lung tryptophan (TRP) levels without change in serotonin (5 HT) or 5-hydroxyindole-3-acetic acid (5-HIAA) levels. This change is organ specific in that TRP levels are not altered in spleen, duodenum, heart or central nervous system (CNS). Acute (48 hour) flunixin treatment decreases lung TRP levels and reverses the AFB1 mediated increase in lung TRP levels. On the other hand, flunixin treatment decreases CNS TRP levels in control mice but not in AFB1 treated mice. Aflatoxin B1 treated mice have an increase in splenic serotonin (5 HT) content. Acute (48 hour) treatment of mice with E. coli lipopolysaccharide (LPS) also increases splenic 5-HT, and AFB1 treatment followed by LPS have a slightly additive effect on spleen 5-HT content. Treatment of mice with LPS increases heart 5-HT, an effect which is not altered in AFB1 pretreated mice. Both LPS and AFB1 per se increases lung TYR levels although the combination of treatments is not significantly different from the control value. Flunixin treatment increases lung tyrosine (TYR) levels, an effect which is not altered by AFB1 pretreatment. Acute treatment with either LPS or flunixin decreases the CNS TRP/TYR ratio; pretreatment with AFB1 prevents those changes in the CNS TRP/TYR ratio. Central nervous system catecholamines are reduced in AFB1 pretreated mice. However, CNS catecholamine changes in AFB1 treated mice are normalized by vitamin E supplementation during the treatment period. PMID- 1906977 TI - Purification and properties of a rat liver phenobarbital-inducible 4 hydroxybiphenyl UDP-glucuronosyltransferase. AB - A phenobarbital-inducible rat hepatic microsomal UDP-glucuronosyltransferase (UDPGT) that catalyzes the glucuronidation of 4-hydroxybiphenyl (4-HBP) has been purified to homogeneity. This UDPGT has an apparent subunit molecular weight of 52,500, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The 4-HBP UDPGT was shown to catalyze the glucuronidation of 4 HBP, 4-methylumbelliferone, and p-nitrophenol but did not react with testosterone, androsterone, morphine, chloramphenicol, 4-hydroxycoumarin, or 7 methoxycoumarin. The apparent Km of 4-HBP UDPGT for 4-HBP was determined to be 0.26 mM and for UDPGA was 1.0 mM. Upon treatment with endoglycosidase H, the 4 HBP UDPGT underwent about a 2000-dalton decrease in subunit molecular weight, suggesting that this protein is N-glycosylated. Additionally, this protein demonstrated immunoreactivity with antibodies raised in rabbit against rat 17 beta-hydroxysteroid and 3 alpha-hydroxysteroid UDPGTs. This work describes the purification and characterization of a 4-HBP UDPGT from rat liver microsomes and, furthermore, provides evidence that suggests that this UDPGT is different from another UDPGT previously shown to react with 4-HBP and chloramphenicol. PMID- 1906976 TI - Differences in the developmental expression of rabbit cytochromes P-450 2E1 and 2E2. AB - The alcohol-inducible CYP2E subfamily in rabbits contains two genes; CYP2E1 encodes the cytochrome earlier termed P-450 3a, and CYP2E2 encodes a cytochrome that is 97% identical in amino acid sequence to cytochrome P-450 (P-450) 2E1. In the present studies, the ontogenic expression of these two cytochromes was examined. In liver, P-450 2E2 mRNA is detectable immediately after birth and reaches slightly greater than the adult level at 2 weeks of age; in contrast, P 450 2E1 mRNA is not detectable until day 14 and increases rapidly to approximately twice the adult level at 5 weeks of age. P-450 2E protein is present in liver immediately after birth, coincident with the appearance of P-450 2E2 mRNA, peaks at 2 weeks, and then, despite the continued elevation in P-450 2E mRNA, decreases to the adult level at 5 weeks. In kidney, P-450 2E2 mRNA is not detectable at any age; P-450 2E1 mRNA, however, is present at 1 week, and the level increases to about half the adult level at 5 weeks of age. P-450 2E protein in this tissue is elevated at 2 weeks, relative to mRNA levels, and reaches approximately half the adult level at 5 weeks. The lack of close correlation between mRNA and protein levels in the liver and kidney of newborn rabbits indicates that the posttranscriptional control of P-450 2E enzyme levels that predominates in adult animals is also operative during the neonatal period. Monooxygenase activities with ethanol and p-nitrophenol as substrates reflect the developmental increase in P-450 2E protein, as well as the appearance and levels of spectrally detectable P-450, cytochrome b5, and NADPH-P-450 reductase in hepatic microsomes. The expression of P-450 2E2, but not P-450 2E1, in early neonates suggests that these two closely related cytochromes may have functional differences that are important during the first few weeks of life. PMID- 1906978 TI - Solubilization of a guanine nucleotide-sensitive form of the P2Y-purinergic receptor. AB - P2Y-Purinergic receptors were solubilized from turkey erythrocyte plasma membranes with the nonionic detergent digitonin. Adenosine 5'-O-(2 [35S]thiodiphosphate) ([35S]ADP beta S) labeled a single population of soluble high affinity sites (Kd = 12.9 nM; Bmax = 4.5 pmol/mg of protein) in an equilibrium binding assay; adenine nucleotide analogs competitively inhibited [35S]ADP beta S binding with a rank order of potency consistent with that for P2Y purinergic receptors. Radioligand binding to solubilized P2Y-purinergic receptors was noncompetitively inhibited by guanine nucleotides with a rank order of potency that was in agreement with the potency order observed for guanine nucleotide-mediated inhibition of [35S]ADP beta S binding in purified turkey erythrocyte plasma membranes. The rate constant for dissociation of [35S]ADP beta S from solubilized receptors was increased 2.3-fold by guanosine 5'-O-(3 thiotriphosphate) (GTP gamma S). Plasma membrane P2Y-purinergic receptors were labeled with [35S]ADP beta S or covalently labeled with the photoaffinity probe 3'-O-(4-benzoyl)benzoyl adenosine 5'-[alpha-32P]triphosphate ([alpha-32P]BzATP) before solubilization and gel filtration chromatography on Superose 12. [35S]ADP beta S- or [alpha-32P]BzATP-labeled species eluted as a single peak of radioactivity of apparent Mr greater than or equal to 300,000. Incubation of the Mr greater than or equal to 300,000 protein species with GTP gamma S before rechromatography resulted in loss of labeling of proteins by [35S]ADP beta S and a shift in apparent size of the covalently [alpha-32P]BzATP-labeled species to a single peak of radioactivity of approximate Mr 70,000. These results suggest that a P2Y-purinergic receptor-guanine nucleotide regulatory protein complex is stable to membrane solubilization with digitonin, even in the absence of prebound agonist. PMID- 1906980 TI - Analysis of immunoglobulin heavy chain delta transcription termination in the production of delta S or delta M mRNA. AB - mRNA encoding secreted immunoglobulin is synthesized either by termination of transcription 3' to secreted terminus sequences and 5' to the membrane terminus sequences or by cleavage of a pre-mRNA transcript containing both secreted and membrane sequences at the appropriate polyadenylation site 5' to the membrane sequences. In vitro "run-on" transcription analysis was used to examine the delta transcription termination patterns in resting membrane IgD expressing B lymphocytes, in KWD2, an IgD-secreting hybridoma, and in TEPC 1017, an IgD secreting plasmacytoma. In resting B cells, transcription terminated in a region 4 to 7 kilobases 3' to the delta M exons. Transcription in the secreting cells continued through the delta M exons, but terminated at more upstream sites. Additionally, an increased loading of polymerases in the region of the delta S exon and its 5' flanking sequence was detected in the secreting cells and was particularly pronounced in TEPC 1017. It is hypothesized that this peak correlates with high delta S mRNA production. PMID- 1906979 TI - Inhibition of arachidonate biosynthesis in hepatoma tissue culture cells by 11 deoxycorticosterone-induced factor. AB - In this work it was demonstrated that the incubation of hepatoma cultured cells (HTC 7288 c) with 11-deoxycorticosterone (DOC) ranging from 0 to 10(-4) M concentration provoked a dose-dependent inhibition in the conversion of [1-14C] eicosatrienoic acid to arachidonic acid. This steroid also produced an increase in the uptake of exogenous 20:3 (n-6) acid. The depressive effect evoked by DOC on delta 5 desaturating activity was reflected on the fatty acid composition changes of the hepatoma cells. The delta 5 desaturase activity was inhibited by a soluble factor that would be induced by the hormone and that was present in the cytosol fraction from DOC-treated cells, corresponding to a low molecular mass below 25 kDa. Presently we report that an 11-beta-OH group on the steroid molecule is not an essential requirement for the production of a delta 5 desaturase inhibitory factor. PMID- 1906981 TI - Early occurrence of immunoglobulin isotype switching in human fetal liver. AB - A cDNA library prepared from a human fetal liver of the first trimester of gestation was screened with Ig C mu, C gamma, C kappa and C lambda probes. Ten heavy chain clones were isolated and characterized by restriction mapping and partial sequencing. The absence of Ig light chain clone and the presence of pre-B specific lambda-like transcripts suggest that the immune compartment of this cDNA library was mostly derived from pre-B cells. Three transcripts of mu, gamma 2 and gamma 4 isotypes contained a V-D-J-C region with an open reading frame and used members of the VHIV, VHIII and VHI families, respectively. Seven clones were derived from sterile transcripts, one C mu and six C gamma. In addition to C mu exons, the sterile mu transcript contained the 5' flanking germline region. By contrast, the gamma sterile transcripts used a 5' sequence that was spliced from the I gamma 1 region onto the first C gamma 1 exon. In addition several of these transcripts were derived from alternative splicing. The simultaneous expression of both sterile and functional gamma transcripts suggests that the switch mechanism operates in normal fetal liver very early in ontogeny. PMID- 1906982 TI - Antibodies of different specificities are self-binding: implication for antibody diversity. AB - Antibodies of the S107/T15 germline family possess variable region structures which allow them to form specific complexes. We extended the investigation of the immunochemical properties of self-binding antibodies (autobodies) to mutant antibodies: U4, which binds DNA, and U10, which has no identified antigenic specificity. U4 differs from the germline S107/TEPC15 autobody by one substitution in the variable heavy chain, which results in a loss of phosphorylcholine binding. Like TEPC15, U4 and U10 are also self-binding. While self-binding of the wild-type TEPC15 antibody is inhibited by free hapten phosphorylcholine self-binding of the anti-DNA antibody U4 is inhibited by DNA and by free nucleotides. The self-binding locus of U4 and U10 was further investigated using peptides derived from the variable region. A 22 residue peptide from the CDR2/FR3 variable heavy chain sequence of the TEPC15 germline structure specifically inhibits self-binding in solid-phase assays. Peptides from unrelated antibodies have no effect on self-binding. The finding of antibodies with identical specificities which are self-binding or not self-binding demonstrates the existence of a novel kind of antibody repertoire diversity controlled by variable sequence structures. PMID- 1906983 TI - Processing fate of protein antigen attached to IgD or MHC molecules on normal B lymphocytes using heterocrosslinked bispecific antibodies. AB - We have studied the internalization, processing and presentation of hen egg lysozyme (HEL) attached to surface IgD (sIgD) or MHC molecules on normal murine B cells, using heterocrosslinked bispecific antibodies (HBA). Nearly all HEL attached to sIgD was internalized within one hour, with at least a portion rapidly entering a chloroquine-sensitive, acidic environment. Degradation and presentation of HEL to hybridoma T cells began several hours after internalization. Degraded HEL was found in the medium after about 6 hr incubation, but at no time were significant amounts of HEL peptides found within the cells. When HEL was attached to class I or class II MHC molecules, its rate of internalization was low. The fraction of antigen bound to MHC molecules that was inside the cell was always low, even at later stages of culture, but the internalized antigen was located in an acidic environment. Degradation and presentation of HEL internalized via MHC molecules followed internalization. No difference was observed in the processing fate of HEL attached to class I or class II MHC molecules. These results suggest that the rate limiting step in antigen processing and presentation is antigen degradation, when the antigen is bound to sIgD, and internalization when bound to MHC molecules. The slow and steady processing of bound or internalized antigen could provide a sustained presence of antigen on the B cell surface and enhance the potential for its presentation to T cells. PMID- 1906984 TI - [Glycine-dependent cryotransformation of Bacillus anthracis by DNA of various plasmids]. AB - The possibility of the 1,8-60,0 Md plasmids DNA transfer into the cells of different Bacillus anthracis strains has been established. A number of parameters of the procedure has been optimized. The including of PEG6000 into the cryomixture in the final concentration 10% has been demonstrated to be vital for increase in transformants yields. Under the described conditions the maximal efficiency of transformation (1,2.10(3)) has been registered for the DNA of the plasmid pUB110. The efficiency of the process decreased concomittant with the size of the transformed plasmids representing 2-4.10(-1) for the plasmid perlicon pXO2 (60 Md). The plasmids obtained by Bacillus anthracis cells retained the functional and structural stability. PMID- 1906985 TI - [Cloning the gene of beta-galactosidase from the industrial strain of Streptococcus lactis 111 in E. coli cells and conjugated transfer of this gene to Streptococcus thermophilus cells]. AB - The ability of the industrial strains of Streptococcus lactis to synthesize the enzyme beta-galactosidase was studied. Five strains among sixteen were found to produce high levels of the enzyme. The beta-galactosidase gene in the most active strain Streptococcus lactis 111 was shown to be located on the 50 kb conjugative plasmid. The plasmid was transferred by conjugation into Streptococcus thermophilus cells and subsequently the gene for beta-galactosidase was studied in transconjugants. The beta-galactosidase gene from Streptococcus lactis 111 was subcloned in Escherichia coli cells on the plasmid pBR322. The gene was localized on the 4.8 kb BgIII fragment of DNA. Following the restriction of DNA by the Sau3A the gene was subcloned on the birepliconed plasmid vector pCB20 capable of replication in the Gram-negative as well as Gram-positive microorganisms. The recombinant derivatives of pCB20 were isolated that carry the beta-galactosidase gene on the DNA fragments of different size. PMID- 1906986 TI - [Study of the dependence of gene expression of plague pathogen plasmid 65MD on the host bacterium genome]. AB - The conjugative cointegrate containing Yersinia pestis 65 Md plasmid coding for the production of traction I antigen and mouse toxin has been transferred into Yersinia pseudotuberculosis, Yersinia enterocolitica and Escherichia coli cells. Analysis of the transconjugants obtained has confirmed the connection of the genetical determinants for the mentioned bacterial products with the 65 Md plasmid. The similar level of fra and tox-genes expression has been found in Yersinia cells while fraction I was not produced in Escherichia coli CA cells. The data on the increased synthesis of fraction I at 40 degrees C as compared with the one at 37 degrees C has been obtained. In some cases the production remained at the same level characteristic of the 37 degrees C. The possibility of formation of different Yersinia Fra+ recombinants in the mixed natural epizootic foci and their role in epizootic infections are discussed. PMID- 1906987 TI - Perioperative total parenteral nutrition in surgical patients. AB - BACKGROUND: We undertook this study to test the hypothesis that perioperative total parenteral nutrition (TPN) decreases the incidence of serious complications after major abdominal or thoracic surgical procedures in malnourished patients. METHODS: We studied 395 malnourished patients (99 percent of them male) who required laparotomy or noncardiac thoracotomy. They were randomly assigned to receive either TPN for 7 to 15 days before surgery and 3 days afterward (the TPN group) or no perioperative TPN (the control group). The patients were monitored for complications for 90 days after surgery. RESULTS: The rates of major complications during the first 30 days after surgery in the two groups were similar (TPN group, 25.5 percent; control group, 24.6 percent), as were the overall 90-day mortality rates (13.4 percent and 10.5 percent, respectively). There were more infectious complications in the TPN group than in the controls (14.1 vs. 6.4 percent; P = 0.01; relative risk, 2.20; 95 percent confidence interval, 1.19 to 4.05), but slightly more noninfectious complications in the control group (16.7 vs. 22.2 percent; P = 0.20; relative risk, 0.75; 95 percent confidence interval, 0.50 to 1.13). The increased rate of infections was confined to patients categorized as either borderline or mildly malnourished, according to Subjective Global Assessment or an objective nutritional assessment, and these patients had no demonstrable benefit from TPN. In contrast, severely malnourished patients who received TPN had fewer noninfectious complications than controls (5 vs. 43 percent; P = 0.03; relative risk, 0.12; 95 percent confidence interval, 0.02 to 0.91), with no concomitant increase in infectious complications. CONCLUSIONS: The use of preoperative TPN should be limited to patients who are severely malnourished unless there are other specific indications. PMID- 1906988 TI - Cystic fibrosis from bench to bedside. PMID- 1906989 TI - Cardiac arrhythmia suppression trial. PMID- 1906991 TI - Antigen shared by HeLa-like human cell line and gastric mucosa. AB - An antigen of human gastric mucosa immunologically related to the antigen of established HeLa-like cell lines (CL-GMA) is described. In gel-immunodiffusion test the antigen was revealed in 10/10 samples of normal gastric mucosa (including all parts of stomach), in 15/16 samples of cancer patients' gastric mucosa 5-10 cm distant from tumor and in 2/2 samples of ulcer patients' mucosa 5 10 cm distant from the ulcer. However, the antigen was undetectable at a distance 1-2 cm from ulcer. Homogenates of 39 embryonic organs and tissues were screened for the presence of CL-GMA. CL-GMA was detected in 7/7 samples of gastric mucosa. The antigen was revealed in trace amounts in 1/4 samples of small intestine mucosa and in 1/4 samples of spleen. Screening of 66 human tumors revealed CL-GMA in 13/16 samples of gastric cancer and in trace amounts in 2 tumors of non stomach localization (larynx and rectum). Analysis of aceton-fixed paraffin sections by means of immunofluorescence revealed be CL-GMA in all parts of stomach. CL-GMA localized in the basal area of high columnar epithelial cells. The antigen was almost or totally undetectable in poorly differentiated adenocarcinomas of stomach and in tumors of other localization. We could not detect CL-GMA in the sera of various cancer patients by means of immunodiffusion and/or dot-blotting. PMID- 1906990 TI - Formation of beta-amyloid protein deposits in brains of transgenic mice. AB - Deposits of beta-amyloid are one of the main pathological characteristics of Alzheimer's disease. The beta-amyloid peptide constituent (relative molecular mass 4,200) of the deposits is derived from the beta-amyloid precursor protein (beta-APP) which is expressed in several different isoforms. The two most prevalent beta-APP isoforms are distinguished by either the presence (beta APP751) or absence (beta-APP695) of a Kunitz serine protease inhibitor domain. Changes in the abundance of different beta-APP messenger RNAs in brains of Alzheimer's disease victims have been widely reported. Although these results have been controversial, most evidence favours an increase in the mRNAs encoding protease inhibitor-containing isoforms of beta-APP and it is proposed that this change contributes to beta-amyloid formation. We have now produced an imbalance in the normal neuronal ratio of beta-APP isoforms by preparing transgenic mice expressing additional beta-APP751 under the control of a neural-specific promoter. The cortical and hippocampal brain regions of the transgenic mice display extracellular beta-amyloid immunoreactive deposits varying in size (less than 5-50 microns) and abundance. These results suggest that one mechanism of beta-amyloid formation may involve a disruption of the normal ratio of neuronal beta-APP isoform expression and support a direct relationship between increased expression of Kunitz inhibitor-bearing beta-APP isoforms and beta-amyloid deposition. PMID- 1906993 TI - [Magnetic resonance tomography markers of tuberous sclerosis without cortical tubera]. PMID- 1906992 TI - [EEG, CCT and MRT in patients after mild and moderate craniocerebral trauma. A study of 102 patients]. PMID- 1906994 TI - [Epileptic prodromal manifestations and episodic affective symptoms: nonspecific complaints or non-convulsive status epilepticus?]. AB - Subjective unspecific complaints presage in some patients with epilepsy a following overt epileptic seizure. It has to be considered whether these epileptic prodromal states are simple partial seizures (epileptic aura) or a status epilepticus non convulsivus. Three patients with epilepsy of different classification and etiology were studied. Their interictally occurring unspezific complaints, the clinical examination and EEG with simultaneous videorecording were documented. In these three cases the results led to the conclusion that the epileptic prodromal states were the expression of a status epilepticus non convulsivus. The management and possible therapeutic intervention are discussed. PMID- 1906996 TI - Hurler's disease with diastematomyelia. AB - A case of Hurler's disease is reported in a child with a gibbous deformity of the lumbar vertebrae L1/L2 and a localized diastematomyelia of the spinal cord at L1/L3. The association of an enzyme disorder affecting connective tissue with spinal cord dysraphism has not been reported before, and may be fortuitous. However, as each condition is rare, the occurrence of both gibbous deformity due to Hurler's and diastematomyelia in the same child, makes it unlikely to be a chance association. We suggest that defective neurulation in this case may be related to mesodermal damage associated with mucopolysaccharidosis. PMID- 1906995 TI - Cyclosporine-induced alterations in the hypothalamic hypophyseal gonadal axis in transplant patients. AB - We evaluated the response of 20 male patients, 13 cadaveric kidney and 7 heart transplant recipients, to the administration of 100 micrograms GnRH (gonadotropin releasing hormone) and 500 micrograms TRH (thyrotropic-releasing hormone). All of the heart transplant recipients and 7 of the kidney transplant patients were receiving a combination of cyclosporine, azathioprine and prednisone; while the 6 remaining kidney transplant patients received azathioprine and prednisone. The patients receiving cyclosporine had decreased plasma levels of prolactin, and manifested a blunted response to TRH administration for prolactin and TSH. The heart transplant patients had a blunted response of LH and FSH to the administration of GnRH. The levels of testosterone were found to be low in all patients regardless of the immunosuppressant therapy. Despite the low testosterone levels, no increment in the concentration of LH or FSH was present. Intramuscular administration of HCG (human chorionic gonadotropin) (Ayerst Laboratories, New York, N.Y.) failed to increase the testosterone concentration in 5 of 6 patients with renal transplants, 3 taking cyclosporine and 3 taking azathioprine. This study suggests that cyclosporine has a selective effect on the hypothalamus and/or hypophysis, resulting in lower baseline levels of plasma prolactin and a pituitary insensitivity to TRH administration. In addition, FSH and LH were low or normal in the presence of low testosterone levels, suggesting that the hypothalamic pituitary gonadal axis is impaired. Furthermore, there may be a direct toxic effect of the immunosuppressant medications on the gonads, manifested as lower testosterone levels and inability to respond to the administration of HCG. PMID- 1906997 TI - [Effects of flecainide in patients with non-sustained ventricular tachycardia and impaired left ventricular function]. AB - Anti-arrythmia efficacy and effects on left ventricular function of flecainide have been evaluated in 9 patients with symptomatic non sustained ventricular tachycardia (NSVT) and left ventricular ejection fraction (LVEF) lower than 30%, respectively detected by Holter monitoring and radionuclide angiocardiography in basal conditions. Seven to eleven days after starting flecainide therapy (100 mg b.i.d.), Holter and radionuclide angiocardiography were repeated. In 56% of patients a ventricular premature beats (VPB) reduction more than 70% was obtained and total VPB suppression was achieved in 33% of patients. Total suppression of NSVT was obtained in 67% of patients; LVEF did not show significant changes. Thus, antiarrhythmic efficacy of flecainide resulted in agreement with the previous reports, whereas no patient developed signs or symptoms of heart failure or pro-arrhythmia. PMID- 1906999 TI - Oral sorbent suppresses accumulation of albumin-bound indoxyl sulphate in serum of haemodialysis patients. AB - Serum indoxyl sulphate, which is markedly accumulated in haemodialysis patients, cannot be removed efficiently by haemodialysis due to its albumin-binding property. To determine whether an oral adsorbent (AST-120) can decrease its serum concentration, AST-120 was administered to haemodialysis patients. The patients given AST-120 showed significantly reduced serum concentration of indoxyl sulphate as compared to control haemodialysis patients, even though the serum concentrations of urea nitrogen and creatinine did not decrease significantly in the patients treated with AST-120. The haemodialysis patients with generalised pruritus showed an amelioration of itching after administration of AST-120. These results showed that AST-120 was effective in reducing the serum concentration of albumin-bound indoxyl sulphate in haemodialysis patients by adsorption of indole, a precursor of indoxyl sulphate, in the intestines, and that it relieved itching in haemodialysis patients with generalised pruritus. PMID- 1906998 TI - [Evaluation of the efficacy and tolerability of quinapril monotherapy in mild and moderate arterial hypertension]. AB - The aim of this single blind, placebo controlled study is to evaluate the efficacy and safety of quinapril in mild to moderate hypertension. Thirty-six patients (from 32 to 64 years old, mean 54.8 +/- 8.84) with diastolic blood pressure (DP) greater than or equal to 96 mmHg and less than or equal to 114 mmHg were enrolled. After a two week wash-out, a placebo was administered for two weeks and than for 12 weeks 20 mg of quinapril u.i.d. At the eighth week if DP was not less than less than or equal to 94 mmHg 40 mg of quinapril was administered. Blood pressure was evaluated at the onset of the study, at the beginning of every step and every 4 weeks. Mean DP and systolic pressure were respectively 159.17 +/- 11.43 and 101.14 +/- 4.39 at the enrolling time, 159.72 +/- 9.41 and 101.86 +/- 3.45 after the wash-out period, 152.78 +/- 9.22 and 98.33 +/- 2.9 after the placebo period, 150 +/- 9.34 and 95.28 +/- 3.52, 144.72 +/- 8.89 and 92.22 +/- 4.32, 140.25 +/- 8.21 and 88.24 +/- 5.27 after 4, 8, 12 weeks of treatment. PMID- 1907001 TI - Distinct cellular expression of pertussis toxin-sensitive GTP-binding proteins in rat cerebellum. AB - Immunohistochemical localization of pertussis toxin-sensitive GTP-binding proteins in rat cerebellum was investigated using antibodies raised against purified G alpha o and synthetic peptides corresponding to specific sequences of G alpha i1, G alpha i2 and G alpha o was detected mostly in the molecular layer but not in the cell body of the Purkinje cells. G alpha i1 and G alpha i2 were found predominantly in the molecular layer and in addition in the cell body of the Purkinje cells. G alpha i3 was not detected in rat cerebellum. Immunoblot analysis demonstrated that in the cerebellum membrane G alpha 0 was most abundant and surprisingly the amount of G alpha i2 was much higher than that of G alpha i1. Thus, each pertussis toxin substrate was found to be expressed differently in rat cerebellum. The different patterns of expression imply that each subtype of GTP-binding proteins may have a specific function in modulating the neuronal activity in rat cerebellum. PMID- 1907000 TI - Asymptomatic autoimmune thyroiditis and thyroid dysfunction in Alport's syndrome. A report of three families. AB - The purpose of this study was to investigate the significance of serum antithyroid antibodies in Alport's syndrome. Thyroid microsomal and thyroglobulin antibodies were assessed in three families with Alport's syndrome for a total of 11 patients and 17 healthy relatives, as well as in 40 haemodialysis patients and in 40 healthy subjects. Thyroid function tests, including the measurement of serum total thyroxine (TT4), total triiodothyronine (TT3), free thyroxine (fT4) and free triiodothyronine (fT3) concentrations, and thyrotropin-releasing hormone (TRH) stimulation tests were performed in all patients and subjects. Among patients with Alport's syndrome, five (45%) had elevated titres of thyroid microsomal antibodies and eight (73%) had positive titres of thyroglobulin antibodies, whereas only one healthy relative (6%) had circulating antithyroid antibodies. Fine-needle aspiration biopsy of the thyroid demonstrated a lymphocytic infiltration that indicated the existence of asymptomatic autoimmune thyroiditis in all five patients with elevated thyroid microsomal antibody titres. The prevalence of antithyroid antibodies in healthy subjects and in haemodialysis patients was 7.5% and 12.5% respectively. Functional tests demonstrated a thyroid dysfunction in four of five patients with asymptomatic autoimmune thyroiditis. Two patients had evidence of subclinical hypothyroidism. Two other patients, both with end-stage renal failure, showed a blunted TSH response to TRH, increased fT4 and elevated borderline fT3. The present study indicates that elevated titres of serum antithyroid antibodies may be detected in patients with Alport's syndrome. These patients are at risk of developing asymptomatic autoimmune thyroiditis and thyroid dysfunction. Subclinical hypothyroidism and, perhaps, preclinical hyperthyroidism may be found in these patients. PMID- 1907002 TI - Contributions of low-threshold calcium current and anomalous rectifier (Ih) to slow depolarizations underlying burst firing in human neocortical neurons in vitro. AB - The slow depolarization that underlies the voltage-dependent burst-firing behavior of human neocortical neurons is mediated by a low-threshold calcium conductance in concert with the anomalous rectifier current, Ih. The slow depolarization could be elicited by depolarization from negative membrane potentials or as a rebound following hyperpolarization. The rebound depolarization was time- and voltage-dependent. Most of the slow depolarization was blocked by inorganic calcium blockers. The remainder of the depolarization and the 'sag' in the hyperpolarizing voltage responses were blocked by extracellular Cs+. PMID- 1907003 TI - Prevention by interleukin-1 of intracisternally injected thyrotropin-releasing hormone (TRH)-induced gastric mucosal lesions in rats. AB - We have recently found that interleukin-1 (IL-1) acts in the central nervous system to potently inhibit gastric acid and pepsin secretion in rats. In the present study, we examined the effects of IL-1 on the development of gastric mucosal lesions induced by intracisternal (i.c.) thyrotropin-releasing hormone (TRH), a neuropeptide known to centrally stimulate gastric secretion. Pretreatment with i.c. injected IL-1 (10 ng/rat) significantly suppressed the severity of TRH-induced gastric erosions. On the other hand, the same dose of i.c. injected IL-1 failed to exert a cytoprotective action for the gastric mucosa against orally administered absolute ethanol. These results suggest that IL-1 has an anti-ulcer effect mainly through its inhibitory action on gastric secretion. PMID- 1907004 TI - [Competition between cleavage nuclei in Drosophila]. AB - Distribution of tissues of XX and XO genotype in gynandromorphs resulting from elimination of unstable ring X-chromosome during initial cleavage divisions was studied. Predominantly XX-nuclei proved to give rise to cell nuclei in tissues of cranial and caudal regions of mosaics. XX nuclei are proposed to be more migrationally active than XO nuclei. PMID- 1907005 TI - Auditory screening of infants. AB - Within the last 20 years, infant hearing screening has progressed from a laudable goal to a state-mandated reality in many areas of the United States. The high risk register provides a means by which history and neonatal physical examination can be used to identify the infant at risk for hearing loss. Two procedures (crib O-gram and auditory brainstem-evoked response) have been the most common methods of screening for hearing loss in the newborn or in intensive care nurseries. Evoked cochlear emissions reportedly are identifiable in 90 to 100% of normal hearing infants. This observation has lead to the use of evoked otoacoustic emissions as a hearing screening procedure with infants. PMID- 1907006 TI - Cost-benefits in orthopaedic technology by using thermoplastics in developing countries. PMID- 1907007 TI - [Current trends in the treatment of diabetic ketoacidotic coma in children (lecture)]. PMID- 1907008 TI - [Changes in the secretion of gonadoliberin, gonadotropins, and ovarian hormones in rats under chronic exposure to low concentrations of methylmethacrylate]. AB - Chronic influence of small concentrations of methylmethacrylate in inhalations (at the level of a maximum permissible dose of 50 mg/m3 and in its 10-fold excess) after short-term enhancement of the hypothalamo-hypophyseo-gonad system (in one month after exposure to a dose at maximum permissible concentration) is quickly followed by suppression of its function. The use of methylmethacrylate for 4 months revealed a decrease in ovarian mass, the blood level of progesterone and a rise of secretion of FSH and LH with a simultaneous decrease in the level of gonad-releasing hormone in the mediobasal hypothalamic structures. It indicates primary gonad damage of the reproductive system and preservation of a normal reaction of the hypothalamohypophyseal factor, responding by activation on the feedback principle. In 4 months a high embryotoxic and teratogenic effect of methylmethacrylate was observed. PMID- 1907009 TI - Removal of an inter-domain hydrogen bond through site-directed mutagenesis: role of serine 176 in the mechanism of papain. AB - A mutant of papain, where an inter-domain hydrogen bond between the side chain hydroxyl group of a serine residue at position 176 and the side chain carbonyl oxygen of a glutamine residue at position 19 has been removed by site-directed mutagenesis, has been produced and characterized kinetically. The mutation of Ser176 to an alanine has only a small effect on the kinetic parameters, the kcat/Km for hydrolysis of CBZ-Phe-Arg-MCA by the Ser176Ala enzyme being of 8.1 x 10(4) /M/s compared with 1.2 x 10(5) /M/s for papain. Serine 176 is therefore not essential for the catalytic functioning of papain, even though this residue is conserved in all cysteine proteases sequenced. The pH-activity profiles were shown to be narrower in the mutant enzyme by up to 1 pH unit at high ionic strength. This result is interpreted to indicate that replacing Ser176 by an alanine destabilizes the thiolate-imidazolium form of the catalytic site Cys25 His159 residues of papain. Possible explanations for that effect are given and the role of a serine residue at position 176 in papain is discussed. PMID- 1907010 TI - Synthesis and biological activity of some 4-substituted pyrimidines and fused pyrimidines. AB - The synthesis of 4-beta-cyanoethylthiopyrimidine 2 and 4-chloropyrimidine 8a was chieved from 4-mercapto-5-acetylpyrimidine (1a). Also the synthesis of thienopyrimidine-7,7-dioxide 6, 4-arylaminopyrimidines 9a-e, 4-alkoxypyrimidines 11a, b, pyrimidoquinazoline 10, thienopyrimidines 19a, b and tetrazolopyrimidine 18 was described. PMID- 1907011 TI - [The immunosuppressive action of contents of Oscillatoria redekai van GOOR (Cyanphyceae)]. PMID- 1907012 TI - Responses to accelerated heavy ions of spores of Bacillus subtilis of different repair capacity. AB - Inactivation, mutagenesis of histidine reversion and the involvement of DNA repair were studied in spores of Bacillus subtilis irradiated with heavy ions at LBL, Berkeley and GSI, Darmstadt. Five groups of ions (from boron to uranium) were used with residual energies from 0.2 MeV/u up to 18.6 MeV/u; in addition, carbon ions were used with a residual energy of 120 MeV/u. Action cross sections of both inactivation and mutagenesis show a similar dependence on ion mass and energy: for lighter ions (Z less than or equal to 10), the lethal response is nearly energy independent (Z = 10) or decreasing with energy (Z less than or equal to 6); these light ions, up to 18.6 MeV/u, induce hardly any mutations. For heavier ions (Z greater than or equal to 26), the lethal as well as the mutagenic responses increase with ion mass and energy up to a maximum or saturation. The efficiency of DNA repair to improve survival and the mutagenic efficiency per lethal event, both, increase with ion energy up to a saturation value which, depending on strain and endpoint, either roughly coincides with the X-ray value or is smaller than that after X-ray treatment. For repair based on recombination events, the increase in the survival effects with ion energy is more pronounced than for that based on repair replication. At energies of 1 MeV/u or below, neither DNA repair nor mutation induction appear to be significant. The results support previous suggestions on the importance of the radial distribution of the energy around the ion track in biological action cross section and the evidence that the entire core of the spore represents the sensitive site in responses to heavy ions. PMID- 1907013 TI - [Ossification of the Achilles tendon. Description of 3 cases]. PMID- 1907014 TI - [Anti-Pseudomonas aeruginosa (Pa) antibiotic therapy and cystic fibrosis]. PMID- 1907016 TI - Home intravenous antibiotic therapy: new technologies. PMID- 1907015 TI - Phase II study of intra-arterial fluorouracil and mitomycin-C for liver metastases of colorectal cancer. AB - Effectiveness, toxicity and complications of 5-fluorouracil (FU) and mitomycin-C (MMC) treatment were analyzed in 30 patients with metastatic colorectal cancer confined to the liver. The treatment schedule was FU 2.0-2.5 g/day for 5 days followed by MMC 10 mg/m2 every 2 h on day 6 to a maximum total dose of 60 mg. Treatment courses were repeated every 6 weeks and were given on an outpatient basis via external pump and arterial port systems. In 30 fully evaluable patients, one complete response, 17 partial responses (overall response rate 60%), and stabilization of disease in 8 patients (26%) were obtained for a median duration of 13 months. Median overall survival was 18.2 months (25.5 months for responding patients, 15 months for nonresponders). Grade 1-2 toxicity (WHO classification) consisted of leukopenia (23%), mucositis (20%), nausea/vomiting (16%), and abdominal pain (10%). Two patients (7%) developed severe mucositis. No life-threatening side effects were observed; in particular, there was no sclerosing cholangitis or chemical hepatitis. Catheter-related problems (occlusion, displacement, rupture, infection) occurred in 10 patients (33%) at a median follow-up time of 12 months. We conclude that intra-arterial FU and MMC constitute an effective, safe, and nontoxic treatment in metastatic colorectal cancer confined to the liver. Catheter-related problems are the most important factors limiting treatment. PMID- 1907017 TI - Strategies and needs for nutritional support in cancer surgery. AB - Nutritional therapy in tumor patients undergoing surgery should be regarded as a supportive therapy. They render the operation tolerable or even feasible, and they have a positive effect on postoperative progress and wound healing. Malnourished patients definitely profit from nutritional therapy. However, the effectiveness of a nutritional regimen should not be overestimated: postoperative progress, wound healing, and complication rate depend not only on nutritional status but also on the nature of the operation, age, and preoperative treatment. As a rule, parenteral feeding is superior to enteral feeding directly after surgery. Enteral nutritive regimens are to be favored when long-term feeding is indicated: in this case the advantages of this type of feeding prevail. PMID- 1907018 TI - Nutritional support of patients with advanced cancer. PMID- 1907019 TI - Percutaneous endoscopically guided gastrostomy in patients with head and neck cancer. AB - In 212 patients with tumors in the head and neck region the nutritional status prior to, during, and following radiotherapy, was determined by body measurements and biochemical and immunological parameters. In 165 orally fed patients the nutritional parameters deteriorated rapidly under radiation and afterwards recovered only slowly and incompletely, 31 patients requiring PEG during radiotherapy. By contrast, 47 patients with a poor initial status who had a prospectively performed percutaneous endoscopically guided gastrostomy (PEG) experienced an amelioration of their nutritional status even before radiotherapy ended. The subjective status of the patients was assessed using the Padilla quality of life index. Here, too, the PEG patients had significantly worse initial values than the orally fed patients. As with the objective indicators of nutritional status a significant deterioration was seen in the orally fed patients during radiotherapy, while the scores of the PEG patients remained constant. We consider early institution of a carefully monitored enteral feeding by PEG useful for stabilizing the nutritional status of patients with tumors in the head and neck region, and therefore recommend, when aggressive multimodal therapy is planned-and particularly if primary malnutrition is already obvious prophylactic performance of PEG prior to the start of therapy. PMID- 1907020 TI - Energy metabolism changes and oxidative attack after hepatic arterial embolization and chemoembolization in thioacetamide-induced cirrhotic livers. AB - Hepatic energy metabolism and oxidative attack were studied after transcatheter arterial embolization (TAE) and chemoembolization (TAC) of the left and median lobes of the liver using thioacetamide (TAA)-induced cirrhotic rats. TAE was carried out using gelatin sponge (1.5 mg/cm3) dissolved in saline solution (SS). TAC was performed by adding mitomycin C (MMC) (1.6 mg/kg body weight) to the previous embolic solution. The energy charge (EC) of embolized lobes decreased from 0.86 to 0.78 and 0.74 1 h after TAE and TAC, respectively, but was restored 3 h later. Adenosine 5'-triphosphate (ATP) and total adenine nucleotide content (TAN) of embolized and non-embolized lobes was also temporarily decreased. Total hepatic blood flow (THBF) of embolized and chemoembolized lobes was reduced in almost 50%, and it took 1 week to become normalized. After TAC (3 and 6 h, respectively), total glutathione (TGSH) content was reduced from 7.02 mumol/g of liver to around 4.5 mumol/g, and malondialdehyde (MDA) content increased from 196.94 nmol/g of liver to values above 300 nmol/g. TAE in cirrhotic livers did not induce any changes in these parameters. In conclusion, after TAE and TAC the hepatic energy metabolism is temporarily altered by ischemia. TAC-induced oxidative attack, in addition to ischemia and MMC, could be one of the mechanisms explaining the effectiveness of this therapy. PMID- 1907021 TI - [Multiple calcifications and ossifications of tendons]. AB - Multiple calcifications and ossifications of tendons are, as a rule, associated with similar lesions of other articular and/or periarticular structures. The nature and multiplicity of these lesions gives them an unquestionable diagnostic and nosological value. Multiple calcifications are part of the apatite arthritis or of diffuse articular chondrocalcinosis. Multiple ossifications of tendons often suggest Forestier's disease and ankylosing spondylitis. PMID- 1907022 TI - Alzheimer's research moves to mice. PMID- 1907023 TI - Controls for lesions of the nigrostriatal dopamine system. PMID- 1907024 TI - DDI approval gets uneasy welcome. PMID- 1907025 TI - Dimerization of human growth hormone by zinc. AB - Size-exclusion chromatography and sedimentation equilbrium studies demonstrated that zinc ion (Zn2+) induced the dimerization of human growth hormone (hGH). Scatchard analysis of 65Zn2+ binding to hGH showed that two Zn2+ ions associate per dimer of hGH in a cooperative fashion. Cobalt (II) can substitute for Zn2+ in the hormone dimer and gives a visible spectrum characteristic of cobalt coordinated in a tetrahedral fashion by oxygen- and nitrogen-containing ligands. Replacement of potential Zn2+ ligands (His18, His21, and Glu174) in hGH with alanine weakened both Zn2+ binding and hGH dimer formation. The Zn(2+)-hGH dimer was more stable than monomeric hGH to denaturation in guanidine-HCl. Formation of a Zn(2+)-hGH dimeric complex may be important for storage of hGH in secretory granules. PMID- 1907027 TI - [Lupus anticoagulants and antiphospholipid antibodies]. PMID- 1907026 TI - Visual motion commands for pursuit eye movements in the cerebellum. AB - Eye movements that follow a target (pursuit eye movements) facilitate high acuity visual perception of moving targets by transforming visual motion inputs into motor commands that match eye motion to target motion. The performance of pursuit eye movements requires the cerebellar flocculus, which processes both visual motion and oculomotor signals. Electrophysiological recordings from floccular Purkinje cells have allowed the identification of their firing patterns during generation of the image velocity and image acceleration signals used for pursuit. Analysis with a method based on a behavioral model converted the time-varying spike trains of floccular Purkinje cells into a description of the firing rate contributed by three visual motion signals and one oculomotor input. The flocculus encodes all the signals needed to guide pursuit. PMID- 1907028 TI - Pathogenesis of hepatic steatosis during total parenteral nutrition. AB - The hepatic toxicity of TPN that is seen clinically appears to be multifactorial in origin. Most patients develop a combination of hepatic steatosis with evidence of cholestasis and abnormalities in liver function. The model that we have studied is one of pure hepatic steatosis since, on repeated study, these rats do not develop any liver function abnormalities. It is unclear whether this is related to the fact that these are short-term experiments, that rat livers respond differently from humans, or that rats do not have gallbladders. It has not been possible to carry these experiments out beyond 3 weeks since the rats develop bacterial colonization of the central lines as well as evidence of line sepsis. thus confounding the issue of hepatic toxicity being due to the TPN or to sepsis. One hypothesis is that hepatic steatosis is an early marker of liver toxicity and that prevention or reversal of hepatic steatosis may protect the liver from further abnormality. Insulin and glucagon seem to play a critical role in the development of TPN-associated hepatic steatosis. Specifically, an elevated portal venous insulin-glucagon molar ratio appears to be the primary stimulus and any treatment that lowers this ratio should diminish hepatic steatosis. The use of glucagon as a treatment modality is new. We have found no evident side effects of low dose glucagon in rats when it is added to the TPN solution. Glutamine has received much attention recently as a nutritional pharmacological agent in ameliorating some of the intestinal complications of parenteral nutrition and is well tolerated when administered appropriately. Intravenous lipid administration is an important nonprotein calorie source, especially when a high dextrose base cannot be used, and plays a role as well in preventing the development of hepatic steatosis. Thus, it is suggested that the clinical treatment of hepatic steatosis during TPN can be safely performed using any one, or a combination, of these modalities and without having to discontinue the TPN infusions. Since we observed no deterioration of liver function in rats receiving TPN for up to 2 weeks, we cannot completely relate these findings and recommendations to the hepatic dysfunction seen clinically with the use of TPN. Additional study will be required before this can be conclusively determined. PMID- 1907029 TI - Dose rate in irregularly shaped high energy photon beams. AB - A quick method of calculating the dose-rate distribution in irregularly shaped beams is presented. This method is partly based on the Cunningham model. The proposed modifications make it possible to avoid the scatter functions in favor of direct use of tissue-phantom ratios and field size coefficients. The problem has been evaluated for photons generated by 10 and 23 MV linacs. The calculated dose rates have been compared with measured ones, and good accuracy has been achieved. PMID- 1907030 TI - Maintenance of superior mesenteric arterial perfusion prevents increased intestinal mucosal permeability in endotoxic pigs. AB - Lipopolysaccharide increases intestinal mucosal permeability to hydrophilic compounds such as chromium 51-labeled edetate (51Cr-EDTA). We sought to determine whether this phenomenon is partly mediated by lipopolysaccharide-induced mesenteric hypoperfusion. We assessed permeability in an isolated segment of ileum by measuring plasma-to-lumen clearances (C) for two probes, 51Cr-EDTA and urea, and expressing the results as a ratio (CEDTA/CUREA). In control pigs (n = 6) resuscitated with Ringer's lactate (RL), mucosal permeability was unchanged during the 210-minute period of observation. In pigs (n = 7) infused with lipopolysaccharide (50 micrograms/kg) and similarly resuscitated with RL, mesenteric perfusion (Qsma) decreased significantly and permeability increased progressively and significantly. When endotoxic pigs (n = 6) were resuscitated with a regimen (RL plus hetastarch plus dobutamine) that preserved normal Qsma, lipopolysaccharide-induced mucosal hyperpermeability was prevented. Resuscitation of endotoxic pigs (n = 6) with RL plus hetastarch provided intermediate protection against both mesenteric hypoperfusion and increased permeability. These data suggest that diminished Qsma contributes to impaired ileal mucosal barrier function in experimental endotoxicosis. PMID- 1907032 TI - Oral-TPN-induced bacterial translocation and impaired immune defenses are reversed by refeeding. AB - Although certain defined diets have been shown to promote bacterial translocation (BT), the ability to reverse diet-induced BT has not previously been investigated. Furthermore, little is known about the effects of defined diets on host immune defenses. To address these questions, we measured BT and immune reactivity in rats fed a normal diet or enteral elemental (ORAL-TPN) diet. After 7 days on the elemental or normal diet, the rats were killed, and BT and mitogen responsiveness to concanavalin A and phytohemagglutinin were measured. In separate experiments, the effects of these diets on in vivo host defenses was measured with a Staphylococcus aureus abscess model. Additional experiments were performed to determine the time required to reverse ORAL-TPN-induced BT and impairment of host immune defenses by reinstituting normal feedings. Administration of the ORAL-TPN diet for 7 days was associated with BT to the mesenteric lymph node complex of all animals, decreased blastogenic response of blood and splenic lymphocytes to mitogens, and decreased ability to control an in vivo infectious challenge with S. aureus. Each of the derangements was reversed by the reinstitution of normal feedings. In summary, the enteral administration of an elemental diet for 7 days is associated with disruption of the gut microflora, BT, and the development of an immunocompromised state, all of which can be reversed by refeeding the animals a normal diet. PMID- 1907031 TI - Modulation of splanchnic vascular sensitivity to angiotensin II. AB - We studied whether the diminished splanchnic vascular response to angiotensin II infusion in portal hypertension could be related to elevated levels of prostacyclin (PGI2). The changes in superior mesenteric artery resistance (RSMA) and systemic vascular resistance (RSYS) during angiotensin II infusion were measured by Doppler flow probe in normal rabbits (NL) and portal hypertensive rabbits (PHT), and in NL and PHT after cyclooxygenase blockade (CO) and after CO and during continuous PGI2 infusion at 300 ng/kg/min. Angiotensin II infusion in NL caused a disproportionately greater increase in RSMA than in RSYS (p less than 0.01). In PHT, angiotensin II response of RSMA was reduced from NL (p less than 0.05). CO dramatically improved the splanchnic response to angiotensin II in PHT animals, but did not significantly alter the RSMA response in NL. PGI2 in NL, NL + CO, and PHT + CO quantitatively established the splanchnic vascular hyporesponsiveness to angiotensin II seen in PHT. We conclude that PGI2 will directly diminish splanchnic response to angiotensin II in NL, and CO will ablate differences in splanchnic response between NL and PHT to angiotensin II. This strongly implies that much of the observed decrease in angiotensin II response in PHT is mediated by PGI2 and that the differences between NL and PHT vascular response is in part the result of circulating vasodilatory substances. PMID- 1907033 TI - Place of phenytoin in treatment of resistant epilepsy. AB - A retrospective therapeutical follow-up of 64 therapy-resistant epileptics treated by phenitoin (DPH) is made chronically. In the study 232 treatment periods of at least two years' duration were analyzed. Distribution of DPH therapeutic combinations was evaluated according to the type of epilepsy, seizure form, seizure frequency, elements of patient compliance, and results of serum level measurements. According to the author's opinions DPH is still one of the most effective agents in the treatment of resistant epilepsy, but in most cases as a constant component of antiepileptic bitherapy. Its pharmacokinetic features and optimal dosage show great individual variability, larger than that of other drugs and, in cases of combined drug regimens, interactions may more frequently be expected. PMID- 1907035 TI - Beyond catastrophic insurance: the future of public funding for long-term care. PMID- 1907034 TI - Community acquired pneumonia: aetiology and prognostic index evaluation. AB - A 10 month prospective study of all adults admitted to Waikato Hospital with community acquired pneumonia was performed to assess aetiology, mortality, hospital stay, and the value of a prognostic index based on that obtained from a British Thoracic Society study. The 92 patients in the survey had a mean age of 56 (range 13-97) years. A microbiological diagnosis was established in 72%; Streptococcus pneumoniae (33%), Mycoplasma pneumoniae (18%), and influenza A virus (8%) were the most common microorganisms. Other causative organisms were Legionella pneumophila (4 cases), Staphylococcus aureus (3), Klebsiella pneumoniae (2), Haemophilus influenzae (2), Nocardia brasiliensis (1), and Acinetobacter calcoaceticus (1). Chlamydia sp, influenza B virus and adenovirus were each found in one case; all were cultured on nasopharygeal aspirates. Aspiration was considered to be the underlying cause in five patients, two with epilepsy and one with pseudobulbar palsy. Five of the six deaths that occurred were in patients over 75 years of age and the other was 69. In four of the six the established causative organisms were Chlamydia sp (1), K pneumoniae (1), and S aureus (2). Patients had a 16 fold increased risk of death if they had two or more of the following on admission: a respiratory rate of 30/minute or more, diastolic blood pressure of 60 mm Hg or less, and either confusion or a plasma urea concentration greater than 7.0 mmol/l. PMID- 1907036 TI - Operating a financially viable Alzheimer's disease treatment unit. PMID- 1907037 TI - Planning long-term care services: a guide for acute care hospitals. PMID- 1907038 TI - Private long-term care insurance: will it work? PMID- 1907039 TI - Cost-effectiveness analysis of family planning programs in rural Bangladesh: evidence from Matlab. AB - The Family Planning Health Services Project in Matlab is often seen as more expensive than similar activities carried out by the government of Bangladesh. At the same time, it as been observed that the project is much more effective. The alleged high cost of the project is said to make it difficult to replicate throughout the nation. Previously, the true costs of the project had not been documented. This study systemically examines the cost of the project and assesses its cost-effectiveness. An experimental design framework is used as a basis for understanding the cost-effectiveness of the project, although a sensitivity analysis lends further support to the relative efficiency of the approach undertaken in Matlab. Although in the aggregate, the Matlab Project is more expensive than the government's family planning program, it is also more effective, generating enough output to offset the extra costs of the intensified delivery system. PMID- 1907041 TI - Termination of immune privilege in the anterior chamber of the eye when tumor infiltrating lymphocytes acquire cytolytic function. AB - Minor H incompatible P815 tumor cells form progressively growing intraocular tumors when injected into the anterior chamber of eyes of BALB/c mice (an immunologically privileged site), but these tumor cells are promptly rejected when injected into the subconjunctival space. In both circumstances, the tumor inoculation site acquires significant numbers of DBA/2-specific precursor cytotoxic T cells (pTc) but only at the subconjunctival site do fully functional cytotoxic T cells (Tc) emerge, and their emergence coincides temporally with rejection of the tumor graft. In the present study, we wished to determine whether pTc can differentiate into Tc within the anterior chamber of the eye and whether the failure of BALB/c mice to reject intraocular P815 tumors is related to this putative block in pTc differentiation. It was previously shown that P815 tumor cells injected into the eyes of MHC-incompatible C57BL/6 mice are able to grow transiently within the anterior chamber and that they are eventually rejected. We have examined the local cytotoxic T cell responses during and after the transient phase of immune privilege that is extended to MHC-incompatible tumor grafts in eyes of C57BL/6 mice. Our results indicate that termination of immune privilege (rejection of the tumor implant) coincides with the detection of fully functional Tc within the tumor-containing eye. Circumstantial evidence suggests that these tumors are infiltrated with DBA/2-specific pTc during the phase of progressive tumor growth and that it is these infiltrating cells that differentiate in oculi into the Tc that effect graft rejection. These findings support the hypotheses that immune privilege in the anterior chamber of the eye is an actively maintained process that suppresses terminal differentiation of pTc and that privilege is abolished if conversion of pTc to Tc is accomplished. PMID- 1907040 TI - Beneficial effect of cyclosporine pretreatment in canine liver ischemia. Enzymatic and electronmicroscopic studies. AB - The effect of cyclosporine on hepatic ischemia was investigated. Hepatic ischemia was produced for 90 min in mongrel dogs. Experimental dogs were divided into three groups as follows: group A (control group), group B (CsA pretreatment group), group C (CsA posttreatment group). CsA was administered at a dose of 10 mg/kg body weight/day for 3 days in the pre- or postoperative period. Survival rates were 61.5% in group A, 84.6% in group B, and 30.8% in group C. Enzymatic activity such as aspartate aminotransferase and lactate dehydrogenase was highest in group C, lowest in group B, and intermediate in group A. Opposite results were obtained for serum albumin concentrations. The mechanisms of the effect was investigated using a 60-min hepatic ischemia model. Serum levels of beta glucosidase and beta-galactosidase in group B were lower than those in group A and group C. Electronmicroscopic specimens taken at 16 h after 60-min hepatic ischemia demonstrated that the extent of ischemic injury was mildest in group B. The present study demonstrated a beneficial effect on hepatic ischemia of CsA administered for 3 days prior to the ischemia. One of the mechanisms for this beneficial effect could be the stabilization of lysosomal membranes. These results suggest that CsA should be administered to a donor before organ harvesting for liver transplantation because of this beneficial effect. PMID- 1907042 TI - The use of myocytes as a model for developing successful heart preservation solutions. AB - The development of a successful method to preserve the heart for relatively long periods (24-48 hr) requires demonstrating successful orthotopic transplantation and long-term survival after preservation. There are, however, multiple variables that may affect the quality of heart preservation, and it is nearly impossible to systematically study all the variables in this complicated model. One model that may be useful to study how preservation parameters affect heart cell preservation is the isolated myocyte preparation. In this study myocytes were isolated from the rabbit heart and the effects of up to 24 hr cold storage on viability measured to determine if this would be a suitable preservation model. Myocytes were stored in various preservation solutions including; EuroCollins (EC), two cardioplegic solutions (Stanford [ST] and Bretschneider solution [HTK]) and the University of Wisconsin solution (UW) with or without the addition of polyethylene glycol. The viability of myocytes was judged by measuring the effects of preservation and rewarming after preservation on cellular morphology (percent rod-shaped cells), ATP concentration, and LDH release. Myocytes preserved in the cardioplegic solutions were least well preserved after 12 and 24 hr storage, as judged by the loss of rod-shaped morphology and lower ATP concentration. Preservation in EC resulted in a decrease in the percent rod shaped cells after 12 hr and 24 hr storage that was greater than obtained in the UW solutions. The best preservation of myocyte morphology and highest content of ATP was obtained in myocytes stored in the UW solutions, especially those containing PEG. The myocyte model of heart preservation shows a loss of cell integrity that is related to the preservation solution (HTK greater than ST greater than EC greater than UW-PEG) and these results are similar to what has been shown in the past with other models of heart preservation. Thus the myocyte model appears to be a useful method to test how many preservation solutions and preservation variables affect heart cell metabolism. In the future, results from these types of studies may find use in developing improved heart preservation solutions for testing in the orthotopic transplant model. PMID- 1907043 TI - In vitro inhibition of platelet aggregation by the liver with UW solution as the preservation fluid. AB - The influence of UW preservation fluid in comparison with that of Euro-Collins and Bretschneider solutions on collagen, adenosine diphosphate and ristocetin induced platelet aggregation was investigated in vitro using platelet-rich plasma of 4 healthy volunteers. The concentrations of the solutions tested were comparable to those that may be used in the transplant situation. 2UW solution inhibited ADP and collagen-induced platelet aggregation--an effect that could be attributed mainly to adenosine and secondarily to penicillin in UW solution- whereas ristocetin-induced aggregation was not affected. Euro-Collins and Bretschneider solutions did not alter platelet aggregation. The inhibition of platelet aggregation by UW may, on the one hand, contribute to bleeding complications after reperfusion and, on the other hand, be responsible for the observed lower incidence of hepatic artery thrombosis. PMID- 1907044 TI - Six-hour porcine liver storage without flushing or perfusion. AB - Livers from normal porcine donors were preserved by surface cooling only, without flushing or perfusion, for periods up to 24 hr. All recipients of livers stored for 6 hr survived until sacrifice at 7 days. In a separate, similar group, survival up to 21 days was noted. Only 2 of 6 recipients survived after 9-hr liver storage, but one of these lived for greater than 120 days. No animals survived longer than 2 days after transplantation of livers stored for 12 or 24 hr. The changes in plasma levels of aspartate aminotransferase of recipients of 6 hr surface-cooled livers were not significantly different from AST levels of recipients of livers stored in University of Wisconsin or Euro-Collins solution as observed in previous studies in this laboratory. At sacrifice after 7 days, there was no histologic evidence of damage after surface cooling. In the light of recent reports of evidence of endothelial and reticuloendothelial damage caused by flushing solutions, it is suggested that surface cooling of the liver may provide adequate preservation for 6 hr in appropriate circumstances. Further studies will be needed to confirm that this method of preservation is applicable to livers removed from brain-dead donors and that it does not cause endothelial damage. PMID- 1907045 TI - Epidemiological observations on theileriosis following field immunisation using infection and treatment. AB - Thirty-seven high grade cattle were immunised against Corridor disease (Theileria parva lawrencei infection) on a farm with a history of heavy and often lethal theilerial challenge. Nineteen cattle were immunised by treating with two doses of long-acting oxytetracyclines given at 20 mg/kg on days 0 and 4 after sporozoite stabilate inoculation, while the other 18 were treated with naphthoquinone buparvaquone, given as a single dose of 2.5 mg/kg simultaneously with stabilate inoculation. All the cattle underwent subclinical theilerial reactions with all but two developing high antibody titres on the IFAT test against T. parva schizont antigen by day 35 after the immunisation. Both buparvaquone and long-acting oxytetracycline appeared equally effective in the immunisation. To date, 26 months later, only two cases of theileriosis parasitologically characteristic of T. p. parva have been reported in the immunised cattle. Following the two cases, investigations showed that when uninfected Rhipicephalus appendiculatus nymphal ticks were deliberately fed on healthy resident cattle on the farm, the resultant adult ticks transmitted acute and lethal theilerial infections to five out of five susceptible cattle. The resultant infections were parasitologically characteristic of T. p. parva infections. Furthermore, the monoclonal antibody profiles of schizont infected cell lines from these infections appeared to be characteristic of T. p. parva. It was thus concluded that resident cattle on the farm could be a potential source of T.p. parva infection which had broken through the immunity of T.p. lawrencei immunised cattle and could constitute a reservoir of theilerial infection for ticks and hence to susceptible stock on the farm. PMID- 1907046 TI - Gross, histologic, cytochemical, and immunocytochemical study of medullary thyroid carcinoma in sixteen dogs. AB - The gross, histomorphologic, cytochemical, and immunocytochemical findings in 16 dogs with medullary thyroid carcinoma were evaluated. Grossly, the neoplasms were encapsulated, firm, lobulated, and grey-white to tan. The typical histologic pattern was groups or sheets of round to polygonal cells with fibrovascular stroma, which was thickened and hyalinized in places. Variants of clear cell (two dogs), giant cell (one dog), and oxyphil cell (one dog) types were also seen. In all 16 dogs, Grimelius-stained sections of the neoplasms revealed intracytoplasmic silver granules; ten tumors contained amyloid and four contained mucin. Immunohistochemically, the neoplasms reacted to AE1/AE3 (n = 13), S-100 protein (n = 5), neuron specific enolase (n = 14), synaptophysin (n = 11), calcitonin (n = 16), somatostatin (n = 4), gastrin (n = 7), and serotonin (n = 6). Only one neoplasm was positive for vimentin. None of the neoplasms reacted to antibodies for neurofilaments, thyroglobulin, insulin, glucagon, or adrenocorticotrophic hormone. Eleven neoplasms contained multiple (two to four) peptides, in various combinations. It was concluded that in dogs, gross and histologic features can be used to distinguish medullary thyroid carcinoma from other thyroid malignancies. Cytochemical and immunocytochemical studies with neuron specific enolase, synaptophysin, and calcitonin can be used to establish the diagnosis of medullary thyroid carcinoma in dogs. PMID- 1907047 TI - Pathology of experimental Schistosoma mansoni infection in the eastern woodchuck (Marmota monax). PMID- 1907048 TI - Anthrax in wildlife in the Luangwa Valley, Zambia. AB - An abnormally high mortality among hippos (Hippopotamus amphibius) in the Luangwa River valley between June and November 1987 and estimated to number more than 4000 deaths was attributed to anthrax. Several other species, particularly Cape buffalo (Syncerus caffer) and elephant (Loxodonta africana), appear to have been affected. A smaller outbreak of anthrax in hippos occurred between August and September 1988, approximately 100 km up-river. A field study was arranged in August 1989 to assess the extent of environmental contamination by Bacillus anthracis and the risks to people in the area, to study possible methods of control and to equip local laboratory staff for continued monitoring of the disease. The study confirmed the enzootic status of the region. The characteristics of the outbreaks of anthrax in 1987 and 1988, and the results of the field study are described. PMID- 1907049 TI - Ovidip as a scab-approved sheep dip. PMID- 1907050 TI - Comparative studies on the vector capacity of the different stages of Amblyomma variegatum Fabricius and Hyalomma rufipes Koch for Congo virus, after intracoelomic inoculation. AB - Groups of nymphs and adults of Hyalomma rufipes and larvae, nymphs and adults of Amblyomma variegatum were infected by intracoelomic inoculation with Congo virus at concentrations of 10(3.5)LD50 (Group A), 10(1.5)LD50 (Group B) and 10(0.5)LD50 (Group C). The infection rates for the different groups were: Groups A, 92-100% for all stages of ticks, except for adult H. rufipes which had 87%; Group B, 56.8, 68.1 and 50.7% for larvae, nymphs and adults of A. variegatum, respectively, and 96.3 and 84.4% for nymphs and adults of H. rufipes, respectively; Group C, 0% for larvae, nymphs and adults of A. variegatum and 8 and 1.7%, respectively, for nymphs and adult adult of H. rufipes. The 1-5% infection threshold was 10(0.5)LD50 for nymphs of H. rufipes and a dose greater than this for all the other stages of the two species of ticks. The 50% infection threshold was 10(1.5)LD50 for larvae and adults of A. variegatum, but less than 10(1.5)LD50 for nymphs of A. variegatum and nymphs and adults of H. rufipes. Peak virus titres obtained for H. rufipes were 10(6.0) for Group A and B nymphs and 10(3.0) for Group A and B adults, and 10(1.0) each for Group C nymphs and adults. For A. variegatum, the peak titres for Groups A, B and C were, respectively, 10(1.0), 10(0.8), and 0 for nymphs and 10(1.5), 10(0.6) and 0 for adults. Sera from 100% (24/24) of rabbits used to feed adult H. rufipes and from 65% (31/48) used to feed nymphs and adult A. variegatum were positive for compliment fixation antibody to Congo virus at a titre of 1:8 from Days 15-35 postattachment of ticks. Viremia in rabbit was detected in 12.5% (3/25) of rabbits used to feed adult H. rufipes. PMID- 1907051 TI - Swainsonine-induced high mountain disease in calves. AB - Swainsonine, an indolizidine alkaloid in the locoweeds (certain species of the Astragalus and Oxytropis genera), was fed to young Holstein bull calves in their milk at high elevation (3090 m), and the incidence of high mountain disease (HMD) was compared with locoweed-fed and control calves. Five of 5 calves fed swainsonine and 5 of 5 calves fed fresh Oxytropis sericea showed outward signs of HMD, which included edema under the jaws, throat area and brisket and gross and microscopic lesions of HMD and locoweed poisoning. Grossly there were HMD lesions, including congestion of the liver, right ventricular hypertrophy, and dilatation and excessive fluid in the thoracic and abdominal cavities. Microscopically, the severe centrilobular lesions in the liver, edema of the pulmonary artery, severe edema and/or fibrosis of the roof of the right atrium were suggestive of HMD. The mild to moderate neurovisceral cytoplasmic foamy vacuolation of selected tissues and cerebellar neuroaxonal dystrophy in all calves fed swainsonine and locoweed were indicative of locoweed poisoning. In control calves, 1 of 6 showed equally severe outward, gross, and microscopic lesions of HMD, but none had any lesions indicative of locoweed poisoning. The ratio of right ventricle to left ventricle wall weights were significantly higher (P = 0.033) for the swainsonine-fed calves (1.4) and the locoweed-fed calves (1.3) compared to the controls (0.9). Scores indicating the severity of HMD from observations prior to necropsy were significantly higher for the swainsonine and locoweed-fed calves compared to controls (P = 0.032).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1907052 TI - [Study of oligohemoglobin solutions in vitro and in vivo]. AB - Solutions of oligohemoglobins (OHb) with middle molecular mass 100 x 10(3) = 400 x 10(3), obtained after polycondensation of hemoglobin with glutaric aldehyde as well as oligohemoglobin modified with pyridoxal-5-phosphate, were studied in vivo and in vitro (plethoric administration, isovolemic metabolic substitution, hemorrhagic shock; at a dose of 0.5-1.8 g/kg of body mass; dogs, rabbits, rats). With increase of the OHb molecular mass period of its circulation in blood was elevated; blood plasma protected OHb from autooxidation; half-life of OHb was about 12-18 hrs in isovolemic metabolic substitution and in hemorrhagic shock and about 5 hrs--in plethoric administration. During circulation molecular mass selection of OHb occurred, where low molecular fraction decreased and high molecular fraction--accumulated; sign and value of human erythrocyte charge were similar both in OHb solutions with concentration up to 5% and in physiological solution. PMID- 1907053 TI - [Use of 4-methylumbelliferryl-alpha-L-iduronide and 4 trifluoromethylumbelliferryl-alpha-L-iduronide for detecting alpha-L-iduronidase deficiencies in human tissue and for rapid prenatal diagnosis of Hurler disease]. AB - Activity of alpha-L-iduronidase was studied in leukocytes of healthy persons, of patients with Hurler disease and of heterozygous carriers of the disease where 4 methylumbelliferyl-alpha-L-iduronide and 4-trifluoromethylumbelliferyl-alpha-L iduronide were used as substrates. 4-Trifluoromethylumbelliferyl-alpha-L iduronide proved to be also a specific substrate of alpha-L-iduronidase and enabled to detect the enzyme deficiency in patients with Hurler disease as well as a decrease of the enzymatic activity in heterozygous carriers of the disease. Using these two substrates prenatal diagnosis of Hurler disease was carried out in fetus which exhibited absence of the enzymatic activity in cell culture from amniotic fluid. The diagnosis was corroborated after analysis of alpha-L iduronidase activity in liver and kidney tissues of the fetus. 4 Trifluoromethylumbelliferyl-alpha-L-iduronide was very effective in express detection of alpha-L-iduronidase deficiency immediately in tissue slices as well as in placenta which is of importance in prenatal diagnosis of Hurler disease. PMID- 1907054 TI - [The formation of infectious scrapie-like structures in the persistence of the agent of amyotrophic leukospongiosis in a brain cell culture]. AB - Electron microscopic analysis of specimens from guinea-pig brain cell cultures infected with amyotrophic leucospongiosis agent (belonging to "unconventional" viruses) revealed accumulation in the culture fluid of abnormal filamentous structures similar to scrapie-associated fibrils (SAF) differing in morphology. Most of these SAF-like structures 10-15 nm in diameter contained helically wound protofilaments with a repeat at certain intervals (50-150 nm). When these structures were inoculated into guinea-pig brain astrocyte cultures they produced dystrophic-destructive changes in some (25%) astrocytes, and their intracerebral inoculation to guinea pigs produced an experimental disease. The abnormal SAF like structures were reisolated from the brains of the inoculated animals which indicated the relationship between these structures and infectivity. PMID- 1907055 TI - Serological investigations for Chagas' disease in Trinidad. AB - A total of 512 sera was examined, using the indirect fluorescent antibody test, for antibodies to Trypanosoma cruzi. No positive reactions were detected even for samples from individuals with related cardiac symptoms. These findings suggest that there is little or no human transmission of T. cruzi occurring in the island of Trinidad. PMID- 1907056 TI - [Ineffectiveness of diltiazem in Duchenne muscular dystrophy: a placebo controlled double-blind study]. AB - In a randomized double-blind study the clinical efficacy of the calcium channel blocker, diltiazem was compared to that of a placebo on the clinical course of Duchenne's dystrophy (DMD) over a 12-month period. Altogether 30 patients, mostly in an advanced state of the disease, were evaluated. The 17 patients in the diltiazem group received 90-360 mg diltiazem per day according to their body weight; the 13 patients of the placebo group received the equivalent amount of a placebo. No significant difference was detected between the two groups regarding muscular power, muscle state, muscular functional ability (Vignos), serum myoglobin and serum creative phosphokinase. PMID- 1907057 TI - Identification of mycobacteria in routine. PMID- 1907058 TI - Determination of lysine damage and calculation of lysine bio-availability in several processed foods. AB - By analyzing lysine and furosine the amount of inactivated lysine in several food systems was determined and the values for available lysine and total lysine were calculated. Considerable heat damage was found in heated cereal products, and in heated milk products, including several formula for children and hospitalized patients. Some products contained more inactivated lysine than available lysine. This may have consequences for the nutrition in low protein consuming populations and leads to errors in predicting the protein quality, e.g., by the recently proposed "Protein Digestibility Corrected Amino Acid Score". PMID- 1907059 TI - Arachidonic acid metabolism: role in inflammation. AB - Arachidonic acid is oxygenated and further transformed into a variety of products which mediate or modulate inflammatory reactions. The cyclo-oxygenase pathway, which is inhibited by nonsteroidal anti-inflammatory drugs, produces vasodilator prostaglandins such as PGE2 and prostacyclin (PGI2) and also thromboxane A4, a potent platelet aggregating agent. Recent work has demonstrated the importance of products formed via various lipoxygenase-catalyzed reactions. Leukotrienes are formed by initial oxygenation at C-5 followed by further transformation to an unstable epoxide intermediate, leukotriene A4 (LTA4). The intermediate can be converted into LTB4 by hydrolysis and into LTC4 by conjugation with glutathione. The formation of the leukotriene, LTA4, is catalyzed by a 5-lipoxygenase possessing both lipoxygenase and LTA4-synthase activities. Unlike other lipoxygenases, this enzyme requires multiple stimulatory factors for maximal activity. These include Ca2+, ATP, and three non-dialyzable cellular components. The cDNAs for human 5-lipoxygenase and LTA4-hydrolase have recently been cloned and the amino acid sequences for the enzymes have been deduced. LTC4 and its metabolites, LTD4 and LTE4, increase vascular permeability and contract airway smooth muscle. Leukotriene B4 causes adherence of neutrophils to endothelial cells and is a potent chemotactic agent. It also stimulates release of lysosomal enzymes and generation of superoxide anion in neutrophils. Oxygenation of arachidonic acid at C-12 and C-15 generates products (5S, 12S-DHETE and 14,15 DHETE) which can modulate various neutrophil functions. A new group of arachidonic acid-derived products was recently discovered. These compounds (lipoxins), formed by oxygenation at C-5 and C-15 and additional reactions, contain a conjugated tetraene structure and three alcohol groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1907061 TI - Detomidine reduces the plasma catecholamine, but not cortisol concentrations in horses. AB - Single doses of the alpha 2-adrenergic sedative-analgesic drug, detomidine (10 micrograms/kg, n = 7; 20 micrograms/kg, n = 9), were administered IV to adult horses. Plasma concentrations of adrenaline, noradrenaline, the catecholamine metabolites 3,4-dihydroxyphenylglycol (DHPG) and 3,4-dihydroxyphenylacetic acid (DOPAC), and cortisol were determined before the medication and 30 minutes after it. The plasma concentrations of noradrenaline and the catecholamine metabolites decreased significantly after administration of both 10 micrograms/kg and 20 micrograms/kg of detomidine. Plasma adrenaline level had a tendency to decrease, but plasma cortisol levels were not influenced. The findings suggest a reduction in sympatho-adrenal activity in horses treated with detomidine. PMID- 1907060 TI - [Liver rupture in peliosis hepatis]. PMID- 1907062 TI - Radiology of the avian skull. AB - A standard radiographic anatomy of the skulls of three genera of birds (Psittacines, Accipitrines, Passerines) is worked out and illustrated by drawings. The African grey parrot is described as a standard. All detectable anatomical structures are identified and set into relationship to discernable structures in cockatoos (Cacatua galerita galerita), common buzzards (Buteo buteo) and mynah birds (Gracula religiosa). PMID- 1907063 TI - Serotonin levels in the hen ovarian follicles after methallibure (I.C.I 33, 828) treatment. AB - The purpose of the present study was to examine the effect of methallibure (MLB), a non-steroid inhibitor of pituitary gonadotrophic activity on serotonin (5-HT) levels in the wall of preovulatory follicles (F1-F4) in the domestic hen. 5-HT was determined spectrofluorometrically. Hens were treated with MLB (10 mg/hen per os) twice a day for 3 successive days. 5-HT was determined in F1-F4 (F1 greater than F2 greater than F3 greater than F4) follicles of the control group, on the next day (MLB-1 group) and 6 days following cessation of MLB administration (MLB 6 group). During MLB treatment egg production was inhibited in all hens. In the MLB-6 group, five hens out of seven took up egg laying on the sixth day after MLB administration. Within each examined group there were no significant differences in 5-HT concentration between F1-F4 follicles. In comparison to the control, MLB caused a significant (P less than 0.01-0.05) increase of 5-HT concentration in F1 (MLB-1 group) and F4 (both MLB-groups). The results obtained indicate that there is a relationship between pituitary activity and 5-HT levels in the preovulatory follicles of the domestic hen. PMID- 1907064 TI - Chronic hepatitis in three young standard poodles. AB - The finding of a morphological similar type of chronic hepatitis in three young and related Standard Poodles is reported. The chronic hepatitis had some resemblance to lobular dissecting hepatitis that is a rare hepatobiliary disorder predominantly described in Standard Poodles, but it could not be concluded whether or not this was actually the diagnosis. However, as the finding of a morphological similar type of chronic hepatitis in three related dogs is rather uncommon, a common genetic or environmental background might be involved in the etiopathogenesis of the disease. PMID- 1907065 TI - Urinary excretion of purines in sheep with experimental orotic aciduria. AB - Urinary excretion of uric acid, hypoxanthine, allantoin, and urea was measured in sheep (Polish Merino, about 20 kg b.w.) with experimental orotic aciduria. The 240 min infusion of 6-azauridine solution into the jugular vein induced a highly significant increase of urinary orotic acid, uric acid and hypoxanthine excretion. No differences were found in relation to excretion of allantoin and urea in examined sheep. It was calculated that renal clearance of uric acid and hypoxanthine increased significantly in response to 6-azauridine infusion. Intravenous infusion of sodium orotate evoked a highly significant elevation of renal urate clearance. No significant change in renal urea clearance was observed. The data suggest that competition between the renal transport of orotate and actively transported purine compounds (uric acid and hypoxanthine) occurs. PMID- 1907066 TI - Haemodynamic effects of change in position and respiration mode during a standard halothane anaesthesia in ponies. AB - The effects of change in position and respiration modes were studied in 5 experimental ponies during a standard halothane anaesthesia. A marked cardiovascular depression (decrease in mean arterial blood pressure, cardiac output, stroke volume and left ventricle work) occurred in recumbent, spontaneously breathing ponies. No significant differences were found between right and left lateral recumbency. The most pronounced cardiovascular depression was observed in the dorsal position. Sternal recumbency appeared to be slightly beneficial (higher systemic blood pressure and arterial oxygenation). Peripheral resistance tended to decrease in the lateral positions (peripheral vasodilatation) but increased slightly in dorsally recumbent ponies. The mean pulmonary artery pressure decreased significantly in the dorsal position. Pulmonary resistance increased slightly in the laterally and the sternally positioned ponies, suggesting a pulmonary vasoconstriction. On the other hand, pulmonary resistance decreased in dorsal recumbency. Arterial oxygenation decreased progressively during anaesthesia but remained always above standing control values. Hypoventilation (increase in arterial carbon dioxide to +/- 60 mm Hg) was observed in all positions. Controlled intermittent positive pressure ventilation (I.P.P.V.) induced a further decrease of all cardiovascular parameters although no significant differences in cardiac indexes were found regarding the spontaneous breathing protocol. In ventilated ponies the greatest cardiovascular depression was again observed in dorsal recumbency. Peripheral resistance increased slightly in the sternally positioned ponies. A gradual time dependent increase in pulmonary resistance was observed. Apparently, the arterial oxygenation improved slightly in all positions (especially the sternal posture) when I.P.P.V. was applied. PMID- 1907067 TI - Standing oestrus, ovarian function and early pregnancy in virgin and repeat breeder heifers. AB - Seventeen virgin heifers (VH) and 14 repeat breeder heifers (RBH) were inseminated in spontaneous oestrus during a total of 86 oestrous cycles. Pregnancy was checked either by non-surgical embryo collections 14 or 17 days after ovulation or by real time ultrasonography 20-26 days after ovulation. The two categories of heifers were compared with respect to duration of standing oestrus, ovarian function and plasma progesterone levels after insemination and during early pregnancy. The results indicate that the duration of standing oestrus was longer in RBHs than in VHs. Ovulation disturbances occurred and were more common among the RBHs than among the VHs. Disturbances in the development of the corpus luteum were noted in both categories of heifers, the RBHs having less luteal tissue volume than the VHs. In general, plasma progesterone levels did not differ significantly between the two categories of heifers. Despite the strict control of oestrus and ovulation as well as additional AI when necessary in this study, a poorer pregnancy result for the RBHs than for the VHs was seen. PMID- 1907068 TI - Influence of age on antisecretory factor inhibition of enterotoxin action in the pig small intestine. AB - The effect of age on antisecretory factor (ASF) inhibition of cholera toxin (CT) and E. coli STa enterotoxin-induced fluid secretion in pig jejunum was investigated in vivo. Comparison was made between 2 week and 8 week old animals. ASF inhibited (P less than 0.05) CT-induced fluid secretion by up to 90% in the 8 week animals (from 18.4 +/- 5.87 mg/mg loop dry weight to 0.74 +/- 0.54 mg/mg loop dry weight). There was no effect of ASF on CT-secretion in the 14 day pigs suggesting that there is a minimum age before ASF is effective. ASF had no significant effect on net fluid transport after STa challenge in pigs from either age group. However, the predominant action of STa was to inhibit absorption and this would not be affected by ASF. PMID- 1907069 TI - Ovine polioencephalomalacia associated with dietary sulphur intake. AB - Fifty-six female crossbred two-month-old lambs were housed in individual cages, and fed a basic ration of barley (59%), soybean meal (5%), and alfalfa (32%) prepared to meet NRC nutrient requirements. Four percent of the diet contained a standard salt mix to which the factors inorganic sulphur (S) and thiamine (B1) were added. Four treatment groups were used: low sulphur and normal thiamine (0.19% S, 13.7 mg/kg B1) low sulphur and high thiamine (0.19% S, 243 mg/kg B1), high sulphur and normal thiamine (0.63% S, 13.7 mg/kg B1), high sulphur and high thiamine (0.63% S, 243 mg/kg B1). All animals had free access to water and were offered 1 kg/animal/day of diet for 14 weeks, when necropsy was undertaken. Seven lambs fed unsupplemented (normal B1) diets containing added sulphur developed clinical symptoms of polioencephalomalacia (PEM) between the 3rd and 7th week of the trial. Morbidity (P less than 0.013) and mortality (P = 0.08) differences were attributed to S administration. None of the B1 supplemented lambs developed clinical signs of PEM. Body weight and relative organ weights did not differ among treatment groups. Serial sections of all brains were examined grossly and microscopically. Nonparametric statistical analysis revealed sulphur related effects in the cerebrum, midbrain and hindbrain (P less than 0.0001), no thiamine related effects or interaction between the factors were seen, except in the amygdaloid body. It was concluded that inorganic sulphur was associated with polioencephalomalacia, and that dietary thiamine may decrease the severity of lesions in some affected areas of the central nervous system. PMID- 1907070 TI - [The effect of the iron content in the culture medium on the nature of the protein spectrum in Neisseria meningitidis]. AB - The protein spectra of Neisseria meningitidis, strain A 208, in the process of its cultivation on solid culture medium based on peptone agar under the conditions of the surplus or deficiency of ions of trivalent iron in the medium. The creation of iron deficiency by the introduction of two iron-binding admixtures, desferol and diethylenetriaminepentaacetic acid (DTPA), was found to lead to the production of two additional proteins with molecular weights of 72 kD and 36-37 kD by meningococcal cells. Of these two admixtures, DTPA more readily stimulated the production of low-molecular protein with a molecular weight of 36 37 kD. This protein was found to be noticeably labile, while protein with a molecular weight of 72-73 kD showed no such lability. As the result of the cultivation of meningococci in iron-deficient medium, the content of protein in microbial residue was 2- to 3-fold greater than that obtained by the cultivation of meningococci in culture medium with the surplus of iron in the form of ferric nitrate. PMID- 1907071 TI - [The ultrastructural organization of Brucella L forms and revertant cultures]. AB - The submicroscopic organization of Brucella cells in the process of L transformation and reversion has been studied. As revealed in this study, at its initial stages L-transformation is accompanied by the loss of cell-wall peptidoglycan and by considerable polymorphism of Brucella cells. Further stages are characterized by the presence of a great number of closed annular membrane structures both in the cytoplasm and outside the cells. At late stages of L transformation the destruction of the cytoplasm and the cells has been found to occur. In revertant cultures the restoration of the cell wall has been noted. PMID- 1907072 TI - [The determination of the location of basic protein I in the Rickettsia prowazekii cell]. PMID- 1907073 TI - Six cases of massive feto-maternal bleeding causing intra-uterine fetal death. AB - Six patients in whom intra-uterine fetal death (IUFD) near term resulted from massive feto-maternal hemorrhage are reported. Two of the mothers were Rh negative, which necessitated the administration of large volumes of anti-D. In order to detect such patients, the Kleihauer-Betke test should be performed in all cases of IUFD of unknown etiology. PMID- 1907074 TI - Thyrotropin-releasing hormone has stimulatory effects on ventilation in humans. AB - Thyrotropin-releasing hormone (TRH) stimulates pituitary thyrotropin synthesis and release and also regulates autonomic nervous system functions by acting as a neuromodulator and neurotransmitter. In experimental animals a stimulation of ventilation by thyrotropin-releasing hormone was shown when applied at central nervous system sites that affect respiratory motor output. It was the goal of our study to investigate the respiratory properties of thyrotropin-releasing hormone on basal and stimulated (i.e. CO2-rebreathing) conditions following systemic thyrotropin-releasing hormone application in healthy humans. Thyrotropin releasing hormone (200 micrograms, 400 micrograms intravenous) initiated a rapid short lasting rise of minute volume, ventilatory air-flow and alveolar oxygen tension under steady state breathing (P less than 0.001). Breathing frequency was less affected, heart rate rose concomitantly (P less than 0.001). While breathing with increasing concentrations of carbon dioxide, minute volume was higher under thyrotropin-releasing hormone than under placebo alone. Further effects (e.g. nausea, dizziness, palpitations) mostly appeared later than respiratory changes and thus may not be responsible for their initiation. Our findings prove systemic thyrotropin-releasing hormone to be a strong respiratory stimulant in man. Response in respiratory output was also accompanied by central nervous system effects (e.g. dizziness, restlessness, augmented vigilance). The mode of thyrotropin-releasing hormone effects on respiration after peripheral administration is still speculative. An augmented sympathetic output or a direct receptor mediated action at central nervous system sites may be responsible, while a peripheral effect cannot be excluded. PMID- 1907075 TI - Carbohydrate ingestion during prolonged running exercise results in an increase of serum cortisol and decrease of gonadotrophins. AB - We tested the hypothesis that improved availability of energy through carbohydrate ingestion could counteract the documented suppression of pituitary gonadal function during prolonged exercise. Nine trained males repeated twice a 36 kilometre running exercise with two weeks interval. During the tests the subjects ingested in a randomized single-blind fashion a total of 1050 millilitres of carbohydrate and placebo solutions. The total amount of ingested carbohydrate was 105 grams. Venous blood samples were taken before the exercise (sample A), immediately after exercise (B), and 2 hours later (C). In the B samples plasma glucose was 14% higher (P less than 0.01) and serum cortisol 13% higher (P less than 0.05) in the carbohydrate than in the control trial. In contrast, the level of LH was 18% (P less than 0.05) and that of FSH 11% lower (P less than 0.05) in the carbohydrate than in the placebo trial. Serum testosterone concentration did not differ between the treatment groups. We conclude that carbohydrate ingestion does not counteract the exercise-associated suppression of gonadotrophin secretion, but results in paradoxical increase of serum cortisol and decrease of LH and FSH, in comparison to placebo-treated controls. The higher cortisol level in carbohydrate group may be secondary to higher insulin levels. PMID- 1907076 TI - Estrogen and diphosphonate treatment provide long-term protection against osteopenia in ovariectomized rats. AB - The goal of this study is to determine whether the previously observed, short term protective effect of estrogen and diphosphonate compounds against osteopenia in ovariectomized (OVX) rats can be maintained for an entire year. Sham-operated control and OVX rats were treated intermittently with vehicle alone, estrogen, or the diphosphonate compounds etidronate disodium (EHDP) and risedronate (NE-58095) for 360 days after surgery. Their proximal tibiae and first lumbar vertebrae were processed undecalcified for quantitative bone histomorphometry. Both skeletal sites in vehicle-treated OVX rats were characterized by decreased cancellous bone volume and increases in most cellular and fluorochrome-based indices of bone formation and resorption. Treatment of OVX rats with estrogen or diphosphonate compounds depressed bone turnover and provided nearly complete protection against cancellous bone loss. Long-term EHDP treatment induced a moderate mineralization defect, as indicated by increased absolute osteoid volume and a high proportion of osteoid surfaces devoid of adjacent osteoblasts. In contrast, NE-58095 had minimal effects on bone mineralization. These findings indicate that diphosphonate compounds and estrogen provide long-term protection against tibial and vertebral osteopenia in OVX rats. They further indicate that diphosphonate compounds merit consideration as an alternative to estrogen for the prevention of postmenopausal bone loss. PMID- 1907077 TI - The immediate and long-term effects of mannitol and glycerol. A comparative experimental study. AB - A prolonged experimental situation of focal vasogenic oedema, producing mild intracranial hypertension, was developed. The aim was to study the immediate and long-term effects of repeated infusions of mannitol and glycerol on intracranial pressure (ICP) and cerebral blood flow (CBF). Eighteen goats were operated on twice to implant: an epidural latex balloon in each cerebral hemisphere to measure ICP; an electromagnetic flowmeter around both internal maxillary arteries (the only cerebral blood input), after tying the extracranial branches, to measure the CBF; and two femoral catheters to measure blood pressure (BP) and for intravenous infusion (IV). Three groups of 6 goats each were formed: A) control; the BP and bilateral ICPs and CBFs were recorded under basal conditions and every 4 hours for 3 days after a cold injury (CI) was provoked; B) 20% mannitol solution 1 g/kg body weight injected every 12 hr starting at 24 hr post-CI; and C) 10.1% glycerol solution 0.5 g/kg body weight, administered as mannitol. Glycerol, as compared to mannitol, presents the following major differences among its immediate post infusion effects: a lesser decrease in ICP, but no rebound phenomenon; lesser elevation of BP; CBF increases more gradually and constantly. Long-term effects with mannitol consisted of a rebound phenomenon observed in ICP during the last 12 hr. In all 3 groups, it was observed that CBF increases in relation to the ICP level. PMID- 1907078 TI - Role of amphipathic helixes in HDL structure/function. AB - In a recent analysis we classified amphipathic helix domains into a minimum of seven distinct classes. Four amphipathic helix classes are found in lipid associating proteins: apolipoproteins, certain polypeptide hormones, polypeptide venoms and antibiotics, and certain complex transmembrane proteins. Three amphipathic helix classes are involved in both intra- and intermolecular protein protein interactions: calmodulin-regulated protein kinases, coiled-coil containing proteins that include the so-called leucine zipper, and globular helical proteins. Three central hypothesis have been developed in our studies of the apolipoprotein class of amphipathic helixes: 1) The "Snorkel" hypothesis proposes that when the amphipathic helix is associated with phospholipid, amphipathic basic residues extend toward the polar face of the helix to insert their charged residues into the aqueous milieu: thus the entirety of the uncharged van der Waals' surface of the amphipathic helix is buried within the lipid. 2) We have formulated a hypothesis that Glutamyl residues located at positions 78 and 111 in apolipoprotein A-I on the nonpolar face of two amphipathic helical domains are critical to LCAT activation. 3) The hinged-domain hypothesis was proposed to explain the structural basis for the quantization of HDL subspecies, protein-protein interactions in HDL, and the HDL disc to sphere transformation. PMID- 1907079 TI - Conformational properties of apolipoproteins studied by computer graphics. PMID- 1907080 TI - Origin of cholesterol and bile acids in the diverted bile of two patients with total small bowel resection. PMID- 1907082 TI - Lipoprotein A-I containing particles. PMID- 1907081 TI - HDL metabolism in HDL deficiency associated with familial hypertriglyceridemia: effect of treatment with gemfibrozil. AB - Plasma high density lipoproteins (HDL) and their major proteins--apolipoprotein (apo) AI and apo AII--are subnormal in most patients with familial hypertriglyceridemia. However, the pathophysiology of low plasma apo AI and apo AII is unclear. The kinetic parameters (turnover) of HDL apo AI and apo AII were studied in six lean patients with primary HDL deficiency associated with familial hypertriglyceridemia and normolipidemic healthy controls. The radioactivity decay curve of 125I labelled HDL was used for assessment of kinetics. Mean plasma apo AI and apo AII were significantly lower (p less than 0.001) in patients than normals (70.4 +/- 2.7 v 106.9 +/- 7.0; 24.2 +/- 1.6 v 39.2 +/- 0.9 mg/dl, respectively). The mean fractional catabolic rates (FCR) obtained from plasma 125I-HDL, apo AI, apo AII radioactivity decay curves and by Berson and Yalow's method (urine/plasma radioactivity ratios) were significantly greater (p less than 0.05) in patients than in controls (0.387 v 0.299; 0.391 v 0.309; 0.361 v 0.275; 0.272 v 0.207/d; respectively). The synthetic rates (SR of apo AI and apo AII were significantly lower in patients than in controls (11.12 v 14.17 mg/kg body weight/d. p less than 0.05; 3.53 v 4.68 mg/kg body weight/d, p less than 0.05, respectively). Each patient was also investigated for HDL and triglyceride metabolism immediately before and after 8 wk of gemfibrozil (1200 mg/d) treatment. Gemfibrozil significantly increased plasma HDL cholesterol, apolipoprotein (apo) AI, and apo AII by 36%, 29%, and 38% from baseline, respectively. Plasma TG decreased by 54%. Gemfibrozil increased synthetic rates of apo AI and apo AII by 27% and 34%, respectively, without changing the FCR.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1907083 TI - [Transurethral incision and fulguration of bladder diverticulum]. AB - We treated 8 patients with bladder diverticula transurethrally. All four quadrants of the diverticular neck which acts as a sphincter and traps residual urine in the diverticulum was incised and the diverticular mucosa was fulgurated until the diverticulum was effaced. The diverticula had markedly shrunk in 2 cases and had totally disappeared in 3. Followup was incomplete in 3 cases. We found that transurethral incision and fulguration of the bladder diverticulum, in combination with transurethral treatment for the bladder outlet obstruction, is a safe, effective and less complicated method. PMID- 1907084 TI - Streptococcal pharyngitis. PMID- 1907086 TI - Combination thrombolytic therapy: a comparison of simultaneous and sequential regimens of tissue plasminogen activator and urokinase. AB - Coronary angioplasty following unsuccessful tissue plasminogen activator (t-PA) therapy for acute myocardial infarction has been associated with a high incidence of subsequent reocclusion of the infarct-related artery, and a relatively high in hospital mortality. In contrast, the combination of t-PA and urokinase, when given intravenously prior to coronary angiography, appears to be associated with a low incidence of post-rescue angioplasty reocclusion. In order to determine whether intraprocedural urokinase, given at the time of rescue coronary angioplasty for failed t-PA therapy, improves long-term patency of the infarct vessel to the same extent as preangiographic, combination t-PA/urokinase therapy, three thrombolytic treatment strategies were retrospectively compared. The first group included 86 patients undergoing rescue angioplasty after t-PA monotherapy (t-PA alone). The clinical and angiographic outcomes of these patients were compared with those of 24 patients who received intravenous or intracoronary urokinase during rescue angioplasty following unsuccessful t-PA therapy (sequential t-PA/urokinase therapy), and with those of 34 patients undergoing rescue coronary angioplasty following unsuccessful therapy with the combination of intravenous t-PA and urokinase (simultaneous therapy). There was no difference in postangioplasty patency rate of the infarct-related artery between the three groups. However, the sequential t-PA/urokinase regimen was associated with a subsequent reocclusion rate that was lower than the rate that occurred in the t PA monotherapy group but higher than the rate in the simultaneous t-PA/urokinase group (13 versus 29 versus 2%, respectively; p = 0.003).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1907085 TI - Coronary artery thrombolysis: comparison of approved agents. AB - Three agents approved for the lysis of thrombi in coronary arteries--alteplase, anistreplase and streptokinase--have undergone critical clinical experimental trials in Europe and the United States. Global comparison of their efficacy shows that alteplase is slightly more effective (71 percent) in restoring patency than anistreplase (60 percent) and streptokinase (58 percent). Streptokinase and anistreplase are allergenic, and repeat administration is not feasible in the short-term, a distinct advantage for alteplase. More accurate dosing of thrombolytic agents and skillful use of aspirin and heparin improve the efficacy of thrombolytic therapy but can also increase the risk of bleeding. A recanalization rate of 90 percent or more could be achieved if the thrombolytic agent is administered within the first hour after thrombosis. Administration this soon after the development of thrombosis may be possible if the agent is given outside the hospital by practicing physicians or, perhaps, paramedics. PMID- 1907088 TI - Indices of reperfusion in patients with acute myocardial infarction using characteristics of the CK-MB time-activity curve. AB - The purpose of this study was to identify indices of coronary artery reperfusion in patients treated with thrombolytic therapy for acute myocardial infarction (AMI) by means of characteristics from the serum creatine kinase (CK) isoenzyme MB time-activity curve. Frequent blood sampling as performed in three groups with a first AMI: 29 patients treated with intravenous thrombolytic therapy who had a patent infarct-related artery with normal flow (TIMI-3) at acute catheterization (reperfusion group); four patients with a persistently closed infarct-related artery (no reperfusion group); and 44 patients who did not receive any therapy aimed at coronary reperfusion (no thrombolytic therapy group). In the latter group we prospectively estimated that 25% would have spontaneous reperfusion. A physiologically based computer-calculated multi-compartment method was used to determine the characteristics of the serum CK-MB time-activity curve. In addition to demonstrating an earlier increase, a shorter time to peak of serum CK-MB and a lower estimated infarct size in the reperfusion group (p = 0.025 to 0.00001), the appearance rate constant (k1) and time from estimated initial increase to peak of CK-MB in the blood stream (tRP) were significantly different from those values in the no thrombolytic therapy group (p less than 00001). A cutoff level indicating reperfusion if k1 was greater than 0.185 or tRP was less than 16.5 hours demonstrated overlapping values between these two groups in only four patients (k1), two patients (tRP), and six patients with a combination.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1907087 TI - Coronary bypass surgery improves global and regional left ventricular function following thrombolytic therapy for acute myocardial infarction. TAMI Study Group. AB - Coronary bypass surgery was performed prior to hospital discharge in 303 (22%) of 1387 consecutive patients enrolled in the TAMI 1 to 3 and 5 trials of intravenous thrombolytic therapy for acute myocardial infarction. Bypass surgery was of emergency nature (less than 24 hours from treatment with intravenous thrombolytic therapy) in 36 (2.6%) and was deferred (greater than 24 hours) in 267 (19.3%) patients. The indications for bypass surgery included failed angioplasty (12%); left main or equivalent coronary disease (9%); complex or multivessel coronary disease (62%); recurrent postinfarction angina (13%); and refractory pump dysfunction, mitral regurgitation, ventricular septal rupture or abnormal predischarge functional test (1% each). Although patients having bypass surgery were older (59.5 +/- 9.8 versus 56.0 +/- 10.2 years, (p less than 0.0001), had more extensive coronary artery disease (46% with three-vessel disease versus 11%, (p less than 0.0001), had more frequent diabetes mellitus (19% versus 15%, (p = 0.048), had more prior infarctions (p less than 0.0001), had more severe initial depression in global left ventricular ejection fraction (48.0 +/- 11.9% versus 51.8 +/- 11.9%, p = 0.0002), and regional infarct zone (-2.7 +/- 0.94 versus -2.5 +/- 1.1 SD/chord, p = 0.02) and noninfarct zone function (-0.36 +/- 1.8 versus 0.43 +/- 1.6 SD/chord, p less than 0.0001) than patients not having coronary bypass surgery, no difference in the incidence of death in hospital (7% surgical versus 6% nonsurgical) or death at long-term follow-up of hospital survivors (7% surgical versus 6% nonsurgical) was noted between groups. Surgical patients demonstrated a greater degree of recovery in left ventricular ejection fraction (3.4 +/- 9.8% versus 0.16 +/- 8.5%, p = 0.036) and infarct zone regional function (0.71 +/- 1.1 versus 0.34 +/- 0.99 SD/chord, p = 0.001) when immediate (90 minutes following initiation of thrombolytic therapy) and predischarge (7 to 14 days after treatment) contrast left ventriculograms were compared than did patients who received only intravenous thrombolytic therapy with or without coronary angioplasty. These data suggest a beneficial influence of coronary bypass surgery on left ventricular function and possibly on the clinical outcome of patients initially treated with intravenous thrombolytic therapy for acute myocardial infarction. PMID- 1907089 TI - Serial antiarrhythmic drug treatment to maintain sinus rhythm after electrical cardioversion for chronic atrial fibrillation or atrial flutter. AB - The sequential use of different types of antiarrhythmic drugs may improve arrhythmia prognosis in chronic atrial fibrillation or flutter after successful electrical cardioversion. The rationale for serial treatment is that the arrhythmogenic mechanism may vary between patients, leading to different responses to 1 specific drug. To investigate this issue prospectively, 127 patients having chronic fibrillation or flutter exclusively, underwent serial drug treatment with flecainide (stage I) followed by sotalol or, if contraindicated, quinidine (stage II) and eventually amiodarone (stage III). Stages II and III were entered after electrical recardioversion for a recurrence during stages I or II, respectively. Calculated on an actuarial basis, the 2-year cumulative percentage of patients free of the arrhythmia increased from 31% after stage I to 63% at the end of serial treatment. To reach this result, a mean of 1.8 +/- 0.8 cardioversions per patient were needed, with 53 patients progressing to stage II and 34 to stage III. Sixteen patients stopped serial treatment prematurely and 15 patients were considered to have intractable atrial fibrillation at the end of stage III. Incidence of proarrhythmia was low. Multivariate analysis disclosed that an older age, in combination with a large number of previous episodes of arrhythmia, a long previous duration of arrhythmia and presence of mitral valve disease, were predictive for medical refractoriness during serial treatment. It is concluded that serial treatment may improve arrhythmia prognosis in atrial fibrillation or flutter, with an acceptable incidence of proarrhythmic events. PMID- 1907090 TI - Comparison of three species of dietary fish: effects on serum concentrations of low-density-lipoprotein cholesterol and apolipoprotein in normotriglyceridemic subjects. AB - Limited information is available comparing the effect of different species of fish on serum low-density-lipoprotein-cholesterol (LDL-C) and apolipoprotein B (apo B) concentrations. We fed 21 normotriglyceridemic males diets containing different species of fish (200 g Dover sole, Chinook salmon, or sablefish) for 18 d in a three-period crossover design. Concentrations of apo B and LDL-C rose on the salmon and sablefish diets compared with the sole diet (P = 0.02 for apo B, 0.08 for LDL-C). These increases were parallel to each other: apo B rose 14% and LDL-C rose 16% on the salmon diet and 17% and 14%, respectively, on the sablefish diet compared with the diet consumed before the study. These results suggest that the consumption of fish with a moderate amounts of n-3 fatty acids may cause a deleterious rise in LDL-C and apo B concentrations in normotriglyceridemic males. PMID- 1907091 TI - Protein-metabolism kinetics and energy-substrate utilization in infants fed parenteral solutions with different glucose-fat ratios. AB - The relative effect of glucose and lipids on whole-body protein-metabolism kinetics was assessed in seven infants undergoing parenteral feeding. Protein intake was kept constant and nonprotein energy was either provided as glucose alone or as an isoenergetic glucose-lipid mixture according to a randomized crossover trial. Protein metabolism and energy-substrate utilization were assessed by a primed, constant L-[13C]leucine infusion, combined with indirect calorimetry. There was a significant difference in the pattern of energy substrate utilization according to regime. Protein turnover (11.3 +/- 0.7 vs 9.8 +/- 0.4 g.kg-1.d-1; P less than 0.05), protein breakdown (8.4 +/- 0.6 vs 7.1 +/- 0.4 g.kg-1.d-1; P less than 0.05), and amino acid oxidation rates (2.7 +/- 0.4 vs 1.4 +/- 0.5 g.kg-1.d-1; P less than 0.05) were higher for the glucose than the glucose-lipid treatment, whereas protein-synthesis rates did not significantly differ. These results suggest that the nature of energy substrates delivered to parenterally fed infants may affect protein metabolism. PMID- 1907092 TI - One-minute endoscopy room test for Helicobacter pylori: interference with 2% glutaraldehyde. PMID- 1907093 TI - Review of duodenal diverticula. AB - Duodenal diverticula occur in 2-5% of patients undergoing barium studies of the upper intestinal tract. Duodenal diverticula are classified into two types: extraluminal or intraluminal. Usually of little clinical significance, they can cause obstruction, cholelithiasis, ascending cholangitis, ulcers, and hemorrhage, and may perforate. Associated intestinal tract malformations have been reported in 40% of patients with intraluminal duodenal diverticula. Diagnosis is made by endoscopy or upper gastrointestinal series. In symptomatic cases, extraluminal diverticula are amenable to surgery, whereas intraluminal diverticula may be either surgically or endoscopically resected. Imaging of the biliary tree should be performed prior to any intervention. PMID- 1907094 TI - Light chain composition of serum granulocyte binding immunoglobulins. AB - Serum granulocyte binding IgG, IgM, and the light chain composition of granulocyte binding immunoglobulins were measured in 58 adult subjects, including 8 normal individuals, 6 with Felty syndrome, 6 with chronic idiopathic neutropenia, 32 with B-cell chronic lymphocytic leukemia (CLL), and 6 with multiple myeloma. An abnormal kappa/lambda ratio of granulocyte binding immunoglobulins was detected in 12 of 32 patients with CLL. Neutropenia in patients with CLL did not correlate with an abnormal kappa/lambda ratio or excess granulocyte binding IgG, but did correlate with granulocyte binding IgM (P less than 0.02). Eight of the 12 patients (5 with chronic idiopathic neutropenia and 3 with Felty syndrome) with an immune neutropenia without underlying neoplastic disorder had light chain restricted granulocyte binding immunoglobulins. Of all patients' sera with light chain restriction, 76% were of lambda light chain isotype. Thus, the frequent detection of light chain restriction of granulocyte binding immunoglobulins is not a reflection of malignancy but is suggestive of the somatic mutation of immunoglobulin light chain genes. PMID- 1907095 TI - Successful treatment of a patient with postpartum factor VIII inhibitor with recombinant human interferon alpha 2a. AB - A patient who had developed a postpartum inhibitor to factor VIII and who did not respond to repeated therapy with steroid and high-dose intravenous gammaglobulin G was treated with one short course of low-dose recombinant interferon alpha 2a (rhIFN) s.c. Within 7 weeks from the start of rhIFN treatment, the inhibitor disappeared. It remains undetectable 8 months after therapy. PMID- 1907096 TI - Enhanced expression of poly(ADP-ribose) synthetase gene in malignant lymphoma. AB - Over-expression of cellular protooncogenes has been proposed to function in the initiation and maintenance of malignancies. In order to distinguish malignant lymphoma from reactive proliferative diseases, we surveyed the expression levels of three protooncogenes(c-myc, c-fos and c-myb) in malignant lymphoma and reactive proliferative diseases. An increased level of c-myc or c-fos mRNA was observed in one case, respectively, out of three malignant lymphomata. The other cases exhibited no enhancement in protooncogenes. These oncogenes are critically regulated during differentiation, but the half-life of c-myc mRNA was very short, and the level of the mRNA decreased to the initial level very quickly. Thus, the high level of the expression of these oncogenes may not always be maintained in all malignant cells. We then examined the level of mRNA for poly(ADP-ribose) synthetase in those cases. An enhanced expression for the synthetase gene was observed in all five malignant lymphomata tested, but no increase in the level of the mRNA was observed in any reactive proliferative cases or normal lymph nodes. These results suggest that enhanced expression of poly(ADP-ribose) synthetase gene seems to be a common characteristic of protopathic malignant lymphoma. By using the characteristics of malignant lymphoma, the level of mRNA for the synthetase may be applicable for differential diagnosis of malignant lymphoma from several pathologically indistinguishable diseases. PMID- 1907098 TI - Lack of response to commercial factor VIII concentrate in hemophilia A. PMID- 1907097 TI - Anticardiolipin antibodies (ACA) are most often not associated with lupus-like anticoagulant (LLAC) in human immunodeficiency virus (HIV) infection. AB - Anticardiolipin antibodies (ACA) and lupus-like anticoagulant (LLAC) have been studied in a group of 142 non-hospitalized and a group of 72 hospitalized HIV infected patients. We observed a variable frequency of ACA positivity ranging from 7.7% to 30.3% according to the groups of patients and the isotype of immunoglobulin fraction containing ACA activity. None of the patients investigated presented a prolongation of the activated partial thromboplastin time (APTT) compatible with the presence of a LLAC. Some patients presented a weak anticoagulant activity only detected by the tissue thromboplastin inhibition (TTI) test. No positive correlation was found between this latter test and ACA. We conclude that, like in syphilitic patients, ACA present in HIV infected patients are most often not associated with LLAC. PMID- 1907099 TI - Interaction of sodium ascorbate with stainless steel particulate-filter needles. PMID- 1907100 TI - Availability of dideoxyinosine. PMID- 1907101 TI - High circulating levels of interleukin-6 in patients with septic shock: evolution during sepsis, prognostic value, and interplay with other cytokines. The Swiss Dutch J5 Immunoglobulin Study Group. AB - PURPOSE AND PATIENTS: We measured the serum concentrations of interleukin-6 (IL 6) in 70 patients with established septic shock caused predominantly by gram negative bacteria. The aims of the study were to determine whether and for how long IL-6 was detectable in the circulation of these patients, to assess whether IL-6 levels were associated with patients' outcomes, and, finally, to examine the interplay between IL-6, tumor necrosis factor (TNF), interleukin-1 beta (IL-1 beta), and interferon-gamma (IFN-gamma). RESULTS: IL-6 was detected in 64% of the patients at study entry but in only 18% on Day 1 and 2% on Day 10. Serum levels of IL-6 were higher (median: 3.5 ng/mL, range: less than 0.1 to 305 ng/mL) in patients dying of fulminant septic shock than in those surviving (median: 0.5 ng/mL, range: less than 0.1 to 135 ng/mL; p = 0.003) or in those with a transient reversal of shock but who ultimately died of a relapse of shock (median: less than 0.1 ng/mL, range: less than 0.1 to 12.5 ng/mL; p = 0.005). However, no cutoff values of IL-6 confidently predicted the outcome of an individual patient. The serum concentrations of IL-6 measured at study entry correlated with the duration of survival (r = -0.51, p = 0.004) and with the levels of TNF-alpha (r = 0.53; p less than 0.0001) but not with the levels of either IL-1 beta (r = 0.01, p = 0.90) or IFN-gamma (r = 0.06, p = 0.60). CONCLUSIONS: These results indicate that circulating levels of IL-6 are detectable in a majority of patients with gram-negative septic shock. Concentrations of IL-6 peaked near the onset of shock and rapidly decreased to undetectable levels within approximately 24 hours in most patients. Levels of IL-6 measured at study entry correlated with levels of TNF and with patients' outcomes. Yet, IL-6 does not appear to be a clinically useful laboratory test for predicting the outcome of an individual patient. PMID- 1907102 TI - Smooth muscle adenosine A1 receptors couple to disparate effectors by distinct G proteins in pregnant myometrium. AB - We have previously shown that adenosine, acting at an A1 receptor, contracts the smooth muscle of virgin guinea pig uterus (M. A. Smith, I. L. O. Buxton, and D. P. Westfall. J. Pharmacol, Exp. Ther. 247: 1059-1063, 1988) and is not coupled to the expected inhibition of adenylate cyclase (M. A. Smith, J. L. Silverstein, D. P. Westfall, and I. L. O. Buxton. Cell. Signal. 1: 357-365, 1989). To probe the importance of contractile actions of adenosine in uterine smooth muscle and to further characterize the signal transduction pathway involved in A1-receptor action, we have studied the adenosine receptor and its coupling in pregnant guinea pig myometrium. Adenosine agonist and antagonist radioligands bind to saturable sites of the A1 subtype homogeneously distributed in the smooth muscle of pregnant guinea pig uterus. Agonist competition of antagonist radioligand binding in both the absence and presence of guanine nucleotide reveals high and low agonist affinity states of the receptor. Pretreatment of tissues with pertussis toxin (PTx) shifts the high-affinity sites to a lower affinity but does not affect low-affinity sites, whereas agonist competition in the presence of guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) is indistinguishable from the control, which is consistent with coupling of A1 receptors to both PTx-sensitive and PTx-insensitive GTP-binding proteins. Adenosine receptor inhibition of adenylate cyclase activity is prevented after pretreatment of the tissue with PTx, whereas increased inositol phosphate production is not. The data presented here are consistent with coupling of the A1 receptor to dual effectors in the pregnant state of the smooth muscle. The unique action of an A1 receptor to contract mammalian smooth muscle and the appearance, only in the pregnant state, of coupling to adenylate cyclase inhibition suggest a role for adenosine in parturition biology. PMID- 1907103 TI - Absorption of lactose from colon of newborn piglet. AB - Piglets in three age groups (1-3, 9-11, and 16-25 days after birth) were used for in vivo colonic perfusions. Studies compared an isosmolar (312 mosM) with a high osmolar (551 mosM) solution and two equimolar substrates (with hexose concentrations of 73.1 mM), lactose and glucose-galactose. From the isosmolar perfusates, lactose absorption was 0.43 +/- 0.04 in the 18-20 day olds and 1.04 +/- 0.2 mumol.cm-1.min-1 in the 1-3 day olds; absorption from the glucose galactose solution was negligible in all age groups (less than 0.05 +/- 0.05 mumol.cm-1.min-1). From the high osmolar perfusate, lactose absorption also exceeded that of glucose and galactose. In a third set of perfusion studies, the concentration of lactose was varied between 15 and 240 mM perfusate. Five-day-old animals absorbed 67% more lactose than 18-day-old animals; the right colon absorbed 57% more than the left. Lactose absorption, correlated with its concentration in the perfusate (r = 0.99), was nonsaturable at concentrations up to 240 mM, and was correlated with the uptake both of sodium (r2 = 0.59 for young and 0.64 for older neonates) and of chloride (r2 = 0.55 for young and 0.31 for older neonates). The results suggest that lactose may be removed from the colon without apparent cleavage by beta-galactosidase. PMID- 1907104 TI - Selective inhibition of vasoconstrictor responses by platelet-activating factor in rat kidney. AB - We examined the effect of platelet-activating factor (PAF) on renal vascular reactivity in the pentobarbital sodium-anesthetized male Wistar rat. Intrarenal infusion of C16-PAF at hypotensive (2.5 ng.min-1.kg-1) or nonhypotensive (0.5 ng.min-1.kg-1) doses caused renal vasodilation and dose dependently antagonized the renal vasoconstrictor responses of intrarenal boluses of angiotensin II (ANG II) greater than norepinephrine (NE) greater than vasopressin (AVP). PAF infusion at the high dose did not alter non-receptor-mediated renal vasoconstriction induced by intrarenal KCl injection. The inhibitory effect of PAF on agonist induced renal vasoconstriction was accentuated by eicosanoid synthesis inhibition (indomethacin or dexamethasone), unaffected by dopamine-receptor blockade (haloperidol) but was totally abolished by PAF receptor antagonism (L-659,989). In contrast, intrarenal infusion of a calcium channel antagonist (nimodipine) or an intracellular calcium channel antagonist (TMB-8) equally inhibited the renal vasoconstrictor responses of ANG II, NE, and AVP. Thus PAF can cause renal vasodilation in the rat kidney and dose-dependently antagonizes the renal vasoconstrictor responses of ANG II greater than NE greater than AVP. The inhibitory effect of PAF on renal vasoconstrictor responses is mediated by PAF receptors and does not appear to be due to a nonspecific membrane effect, reduction in calcium mobilization, or the release of vasodilatory eicosanoids or dopamine. PMID- 1907105 TI - Responses to renin inhibition in conscious primates. AB - A method for the measurement of renal clearances was adapted in a novel manner to the conscious marmoset. Twenty-four hours before an experiment, animals underwent surgery for placement of both femoral arterial and venous catheters. A catheter was also implanted into the urinary bladder through the abdominal wall. The urinary catheter consisted of two tubes. One tube was connected to a pump, which removed the urine, while the other tube remained open to prevent the formation of a vacuum inside the bladder. Using this technique, we kept renal clearances stable for at least 3 h. All catheters were removed the day after the clearance experiment, and the bladder was reconstructed using microsurgical techniques. The bladder operation did not appear to produce lasting anatomical or functional changes, since the animals were able to void spontaneously and, after 3 mo, the bladder had regained its normal size and shape. Reimplantation of both the vessel and bladder catheters at this time allowed for an additional study of renal clearances within the same animals. Administration of the renin inhibitor CGP 29287 (1 mg/kg) to furosemide-pretreated conscious marmosets lowered blood pressure and increased renal blood flow. Glomerular filtration rate remained unchanged by CGP 29287, leading to a fall in the effective filtration fraction. Urinary volume and urinary sodium excretion also were unchanged by the renin inhibitor. We describe a novel method for the study of renal clearances in a small conscious primate and suggest that the renin-angiotensin system plays an important role in the control of renal function in the sodium-depleted marmoset. PMID- 1907106 TI - Renal blood flow response to angiotensin II infusions in conscious pregnant rabbits. AB - Renal blood flow (RBF) was measured in conscious rabbits while nonpregnant and during pregnancy using chronically implanted ultrasonic transit-time flow probes. The effects of the cyclooxygenase inhibitor meclofenamate (5 mg/kg) and the angiotensin-converting-enzyme inhibitor captopril (5 mg/kg) on basal RBF and on RBF responses to systemic angiotensin II infusions (2.5-80 ng.kg-1.min-1) were determined. Basal RBF declined (P less than 0.001 to P less than 0.005) with meclofenamate by 9-16% in pregnant (n = 7) and by 10% in nonpregnant (n = 7) rabbits. Captopril increased (P less than 0.05 to P less than 0.01) RBF by 9-11% in pregnant (n = 5) and by 12% in nonpregnant (n = 5) rabbits. There was no effect of the vehicle (normal saline) on RBF. The reduction in RBF (% from baseline) in response to infused angiotensin II was attenuated in pregnant compared with nonpregnant rabbits. Pretreatment with meclofenamate enhanced the renal vasoconstrictor action of angiotensin II in a similar fashion in both pregnant and nonpregnant rabbits. Captopril or saline did not alter the RBF responses to angiotensin II infusions. Mean arterial pressure was lower in pregnant (78 +/- 3 mmHg, n = 7) vs. nonpregnant (88 +/- 5 mmHg, n = 10) rabbits, suggesting lower total peripheral resistance. The data indicate 1) chronically implanted ultrasonic flow probes can be an effective tool for monitoring RBF in conscious rabbits, 2) prostaglandins and the renin-angiotensin system influence basal RBF in conscious rabbits, and 3) the renal vasoconstrictor effect of angiotensin II is blunted in pregnant rabbits and this attenuated response appears to be independent of prostaglandins. PMID- 1907107 TI - LTD4 and bradykinin evoke endothelium-dependent relaxation of the renal vein: dissimilar mechanisms. AB - This study's goals were to define the vasomotor effects of the peptide leukotriene (LT)D4 on norepinephrine (NE)-contracted isolated rings of canine renal vein (RV) and to compare these influences with those of bradykinin (BK). Canine RV rings were connected to isometric force transducers and bathed in Krebs Ringer bicarbonate buffer containing indomethacin (10-5M). LTD4 and BK evoked dose-dependent decreases in tone of NE-contracted RV rings that were abolished by physical removal of the endothelium. Relaxation of the RV ring produced by glyceryl trinitrate (GTN) was slightly enhanced or unaltered after endothelium denudation. Reduced human hemoglobin (Hb, 10(-6) M), NG-monomethyl-L-arginine (L NMMA, 300 microM) and methylene blue (MB, 10(-6) M) had no effect on LTD4-induced venomotor relaxation, whereas they significantly decreased the vasorelaxant effect of BK. In contrast, endothelium-dependent relaxation of renal arterial rings produced in response to both LTD4 and BK was markedly attenuated in the presence of either reduced Hb (10(-6)M) or MB (10(-6) M). MB significantly attenuated venorelaxant responses to GTN (10(-8) to 10(-6) M). The ATP-sensitive K(+)-channel blocker glybenclamide (10(-6)M) inhibited relaxation of the RV induced by cromakalim (5 x 10(-8)M) but had no effect on LTD4-evoked relaxation. These data indicate that endothelium-dependent relaxation of the RV elicited by BK is dependent on "classic" endothelium-derived relaxing factor (EDRF) considered to be nitric oxide (NO) or an unstable nitroso compound that ultimately liberates the NO radical.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1907108 TI - Vascular responses of umbilical-placental circulation to vasodilators in fetal lambs. AB - It has been suggested that the umbilical-placental circulation is maximally vasodilated under normal conditions. To test this hypothesis, we investigated the effect of vasodilators on umbilical-placental vascular resistance. In nine chronically instrumented fetal lambs, catheters were placed in the descending aorta, umbilical artery, umbilical vein, and inferior vena cava. Umbilical placental blood flow was measured by an electromagnetic flow probe placed around the common umbilical artery. Forskolin and nitroglycerin both dilated the umbilical-placental circulation, causing a dose-dependent decrease in umbilical placental resistance to approximately 80% of baseline, indicating that the umbilical-placental circulation has some dilatory reserve. Both the adenosine 3',5'-cyclic monophosphate and the guanosine 3',5'-cyclic monophosphate mechanisms, which are directly stimulated by forskolin and nitroglycerin, respectively, are functional in the umbilical-placental circulation. However, the vasodilators prostacyclin and adenosine, which act through specific cell membrane receptors, have no effect on the umbilical-placental resistance. The inability of these agents to dilate the umbilical-placental circulation could be due to a lack of the appropriate receptors in the umbilical-placental vasculature. PMID- 1907110 TI - Branhamella catarrhalis and croup: toxicity in the upper respiratory tract. AB - Branhamella catarrhalis has gained increasing recognition as a pathogen in the respiratory tract. During the past 18 years, since its transfer from the genus Neisseria, it has been associated with infection in cavities of the respiratory tract (sinuses and middle ear). It has been recognized as playing a role in laryngitis. Its isolation in large numbers from the surface and core of acutely and chronically infected tonsils indicates a possible role in these infections. Croup (two patients reported here) can now be added to this list. The toxic potential of B catarrhalis, its movement from commensal to pathogen for the upper respiratory tract, and the pathogenic mechanisms by which this has occurred are reviewed. PMID- 1907109 TI - Trypanosomatid isolates from Honduras: differentiation between Trypanosoma cruzi and Trypanosoma rangeli. AB - With the aim of identifying and differentiating Trypanosoma cruzi from Trypanosoma rangeli, culture epimastigotes from 30 Honduran trypanosomatid isolates were analyzed by susceptibility to complement lysis, reactivity to lectins, reactivity to monoclonal antibodies specific for T. cruzi, and isoenzymatic electrophoretic patterns. Using these four methodologies, 27 of the 30 trypanosomatid isolates, as well as 5 clones, were identified as T. cruzi, whereas the remaining three isolates were classified as T. rangeli. None of the isolates presented mixed trypanosome species. Results indicate that both trypanosomatid species circulate in Honduras and that any of the four methods employed may be used to reliably differentiate T. cruzi from T. rangeli. PMID- 1907111 TI - Continuous measurement of intraarterial pHa, PaCO2, and PaO2 in the operating room. AB - Miniaturized sensors based upon the principles of optical fluorescence can measure the pH, PCO2, and PO2 of liquid or gas media. A prototype of a three component fiberoptic sensor has been developed for intraarterial application by CDI, 3M Health Care, Irvine, California. We report the first study of this continuous intraarterial monitor in patients undergoing surgical procedures under general anesthesia. Fourteen patients participated in the study. The fiberoptic sensor was calibrated before insertion and then passed through an existing 18 gauge radial artery cannula. Blood samples were drawn at frequent intervals through the same cannula for in vitro blood gas analysis. For each of the 87 arterial blood gas samples obtained, the in vitro values of pHa, PaCO2, and PaO2 were compared with simultaneous readings from the fiberoptic sensor. For pHa, the mean error (error = fiberoptic value minus in vitro value) or "bias" of the fiberoptic data was -0.032 and the standard deviation of error or "precision" was 0.042. For PaCO2, the bias was -3.8 mm Hg and the precision was 4.7 mm Hg. For PaO2, the bias was -9.0 mm Hg and the precision was 23.3 mm Hg. For PaO2 values less than 175 mm Hg, the bias was -8.5 mm Hg and the precision was 8.3 mm Hg. Expressed in terms of percentage errors, the bias +/- precision values were 11.5% +/- 13.3% for PaCO2, and -6.2% +/- 10.0% for PaO2. The duration of the surgical procedures ranged from 1.6 to 8 h with an average of 4.2 h.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1907112 TI - The relationship between the arterial to end-tidal PCO2 difference and hemoglobin saturation in patients with congenital heart disease. AB - In right-to-left (RL) intracardiac shunting, the venous blood that is added to the oxygenated blood in the left heart is both poor in oxygen and rich in carbon dioxide. Thus, any given degree of arterial desaturation is associated with an obligatory arterial to end-tidal carbon dioxide tension difference (PaCO2- PETCO2). This paper presents a theoretical analysis of the relationship between PaCO2-PETCO2 and arterial hemoglobin saturation (SaO2) in cyanotic heart disease. Using the shunt equation as a starting point, a curvilinear, negative correlation between PaCO2-PETCO2 and SaO2 can be demonstrated. The slope of the regression of PaCO2--PETCO2 against SaO2 is shown to be positively correlated to Hb concentration, PaCO2, and the respiratory quotient R. The slope of the regression is also slightly increased at relatively high SaO2s and at high inspired oxygen fractions, although these latter factors are of lesser significance. However, in addition to the above primary effects of RL shunting, secondary effects may occur if pulmonary perfusion is reduced sufficiently to cause "alveolar hypoperfusion," which also creates an alveolar dead space. Primary and secondary effects are additive. This theoretical analysis is illustrated with a study of 27 children with congenital heart disease. Their lungs were ventilated with a Servoventilator 900 C, and carbon dioxide single-breath tests were obtained on-line with the use of a computerized system based on the Siemens-Elema carbon dioxide analyzer 930. Blood was sampled for PaCO2 measurement and arterial Hb saturation was measured by pulse oximetry (SpO2).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1907113 TI - Pulmonary vasoregulation by cyclooxygenase metabolites and angiotensin II after hypoperfusion in conscious, pentobarbital-anesthetized, and halothane anesthetized dogs. AB - The authors investigated the extent to which endogenously produced metabolities of the cyclooxygenase pathway and angiotensin II modulate the pulmonary vascular response to increasing pulmonary blood flow after a period of systemic and pulmonary hypotension and hypoperfusion (defined as posthypoperfusion) in conscious, pentobarbital-anesthetized, and halothane-anesthetized dogs. The authors tested the hypothesis that vasodilator metabolites of the cyclooxygenase pathway offset the vasoconstrictor influence of angiotensin II to prevent pulmonary vasoconstriction posthypoperfusion. Baseline and posthypoperfusion pulmonary vascular pressure-cardiac index (P/Q) plots were constructed by stepwise inflation and deflation, respectively, of a hydraulic occluder implanted around the inferior vena cava to vary Q. In intact (no drug), conscious dogs, the pulmonary vascular P/Q relationship posthypoperfusion was not altered significantly compared with baseline. In contrast, after cyclooxygenase inhibition, active flow-independent pulmonary vasoconstriction (12-17%; P less than 0.01) was observed posthypoperfusion, and this response was abolished entirely by angiotensin converting-enzyme inhibition. During pentobarbital anesthesia, significant pulmonary vasoconstriction (27%; P less than 0.01) occurred posthypoperfusion in the no-drug condition. However, the magnitude of the posthypoperfusion vasoconstriction was not increased by cyclooxygenase inhibition, nor was it reduced by converting-enzyme inhibition. During halothane anesthesia, pulmonary vasoconstriction was not observed posthypoperfusion in the no-drug condition, but it was unmasked (8-13%; P less than 0.05) by cyclooxygenase inhibition and attenuated partially by converting-enzyme inhibition. These results indicate that cyclooxygenase metabolites and angiotensin II exert opposing vasodilator and vasoconstrictor effects, respectively, on the pulmonary circulation of conscious dogs posthypoperfusion. These competing mechanisms are active during halothane anesthesia but are abolished during pentobarbital anesthesia. PMID- 1907114 TI - Nasal provocation test with lysine acetylsalicylate in aspirin-sensitive patients. AB - The authors have studied nasal provocation testing (NPT) with aspirin in 45 aspirin-sensitive patients (40 affected by nasal polyposis) and in 38 aspirin tolerant patients (27 affected by nasal polyposis). The test was positive in 37.7% of aspirin-intolerant subjects, but only in 7.9% of subjects in the control group (P less than .01). PMID- 1907115 TI - Airborne infection. Theoretical limits of protection achievable by building ventilation. AB - Of 67 office workers 27 (40%) had documented tuberculin skin test conversions after an estimated 4-wk exposure to a coworker with cavitary tuberculosis. Worker complaints for more than 2 yr before the tuberculosis exposure prompted investigations of air quality in the building before and after the tuberculosis exposure. Carbon dioxide concentrations in many parts of the building were found to be above recommended levels, indicating suboptimal ventilation with outdoor air. We applied a mathematical model of airborne transmission to the data to assess the role of building ventilation and other transmission factors. We estimated that ventilation with outside air averaged about 15 feet 3/min (cfm) per occupant, the low end of acceptable ventilation, corresponding to CO2 levels of about 1,000 ppm. The model predicted that at 25 cfm per person 18 workers would have been infected (a 33% reduction) and at 35 cfm, a level considered optimal for comfort, that 13 workers would have been infected (an additional 19% reduction). Further increases in outdoor air ventilation would be impractical and would have resulted in progressively smaller increments in protection. According to the model, the index case added approximately 13 infectious doses (quanta) per hour (qph) to the office air during the exposure period, 10 times the average infectiousness reported in a large series of tuberculosis cases. Further modeling predicted that as infectiousness rises, ventilation would offer progressively less protection. We conclude that outdoor air ventilation that is inadequate for comfort may contribute to airborne infection but that the protection afforded to building occupants by ventilation above comfort levels may be inherently limited, especially when the level of exposure to infection is high. PMID- 1907116 TI - Capsaicin inhibits airway hyperresponsiveness but not lipoxygenase activity or eosinophilia after repeated aerosolized antigen in guinea pigs. AB - To evaluate the role of tachykinins in airway hyperresponsiveness following repeated aerosolized antigen challenge in guinea pigs, we treated 12 guinea pigs with capsaicin (105.6 mg cumulative dose given subcutaneously over 5 days) after sensitization to ovalbumin (OA) and before three repeated OA aerosol challenges per wk for 4 to 5 wk. Ten guinea pigs received identical OA sensitization and challenges without capsaicin treatment, and four of eight nonsensitized controls received capsaicin followed by saline challenges. Capsaicin treatment did not alter antibody responses to OA as assessed by passive cutaneous anaphylaxis, nor did it alter lipoxygenase products from OA-stimulated bronchial tissue in vitro. Capsaicin completely inhibited the increased pulmonary resistance (RL) to acetylcholine produced by repeated aerosolized OA, whereas it did not alter baseline RL or acetylcholine responses of controls. Capsaicin did not alter airway eosinophilia induced by repeated aerosolized OA. We conclude that neuropeptides play an important role in antigen-induced airway hyperresponsiveness without altering antibody levels, lipoxygenase mediator production, or airway eosinophilia. PMID- 1907117 TI - Senile dementia: a threshold phenomenon of normal aging? A contribution to the functional reserve hypothesis of the brain. AB - Neurochemical investigations with normal aging brains show that in the first 70 years of life no major changes of the glycolytic pathway can be observed. Only in the following decades does a significant decrease of brain metabolic turnover occur. Changes in nerve cell size, one of the most relevant parameters in evaluating a diffuse nerve cell atrophy, appear in the brain cortex not earlier than between 85 and 94 years of age; a 21% nerve cell shrinkage is the mean. The results demonstrate that a significant decrease in turnover of the glycolytic pathway is followed by a significant but moderate shrinkage of the nerve cells after a delay of 10-15 years. Similar investigations in brains from senile demented subjects demonstrate that the change in glycolytic turnover is much more a quantitative than a qualitative phenomenon. In comparison with age-matched controls a decrease in glycolytic turnover of more than 60% is observed. Morphometric investigations of the nerve cell sizes in the brain cortex of senile demented subjects showed a decrease of 45-55% when compared with age-matched controls. When normal aging is compared with senile dementia it seems that old age dementia is a threshold phenomenon which starts if the glycolytic turnover drops below 50% of its value in young healthy adults. Physiological aging, however, stays within the range of the reserve capacity of normal brain performance. In conclusion, it seems that the exhaustion of the functional reserve capacity may shift an aging brain into a dementia syndrome. PMID- 1907118 TI - Monoclonal B-cell proliferative disorders and aging. PMID- 1907119 TI - [Pharyngoesophageal diverticula. Results of a series of 41 diverticulectomies]. AB - The aim of this study was to evaluate the short-term results of surgical treatment of pharyngoesophageal diverticulum (POD). From 1970 to 1988, 41 patients underwent diverticulectomy for POD and in 10 cases, myotomy was associated. Patients were divided into two groups: group I (10 cases) in which patients required nutritional and/or respiratory preparation before surgery; group II (31 cases) in which patients underwent surgery without delay. In group I, the mean age was 79.8 years and the delay before diagnosis and treatment was 80.6 months versus 66 years and 34.6 months in group II. In group I, all patients presented with weight loss and suffered from pulmonary infections. Mortality in this series was 3 patients (7.3%) and 4 complications occurred. In group I, mortality was 2 patients (20%) and 3 complications occurred (30%), while in group II, mortality was one patient (3.2%) and one complication occurred (p less than 0.05). Long-term results showed 90% of good results. Local complications might be avoided by perfect surgical procedure. The mortality can be explained by the patients' previous status and the long history of disease. PMID- 1907120 TI - Feedback of laboratory usage and cost data to clinicians: does it alter requesting behaviour? AB - In a 1 year prospective study we evaluated the effect of feedback of laboratory data on the requesting behaviour of physicians in general medicine. Data on within-hours and out-of-hours clinical chemistry laboratory usage and revenue expenditure for inpatients and outpatients, expressed in terms of clinical workload, were supplied monthly to a group of three consultant physicians in general medicine. With these data the physician could monitor his performance over a period of time and compare it with that of his peers. Two consultants in general medicine who received no information served as controls. Over a period of 6 months, there was a 25%, 13% and 18% decrease in tests (P less than 0.01), requests (P less than 0.05) and revenue expenditure (P less than 0.01) per outpatient visit, respectively, in the intervention group of physicians following the introduction of feedback when compared to their baseline period and to the control group. The decrease (P less than 0.01) was in the commonly requested and 'seemingly cheap' tests. There was no significant change in laboratory use and expenditure on inpatients. The feedback of laboratory data was acceptable to the physicians, raised their awareness of laboratory usage and costs and decreased laboratory workload and expenditure. PMID- 1907122 TI - A specific assay for serum intestinal alkaline phosphatase utilizing fluorescein labelled monoclonal antibody and antifluorescein antibody coupled to magnetic particles. PMID- 1907121 TI - Enzymatic measurement of 3-hydroxybutyrate in extracts of blood without neutralization. PMID- 1907124 TI - Levels of environmental pollutants in male and female flounder (Platichthys flesus L.) and cod (Gadus morhua L.) caught during the year 1988 near or in the waterway of Glomma, the largest river of Norway. I. Polychlorinated biphenyls. AB - Levels of polychlorinated biphenyls, PCBs, in liver samples of 111 and 121 flounder (Platichthys flesus L.) and cod (Gadus morhua L.), respectively, were determined gas chromatographically by quantification of 9 individual PCB congeners. The congeners were 28, 52, 101, 118, 153, 138, 180, 170, and 209 (IUPAC numbering system, Ballschmiter and Zell 1980). The fish were caught during 1988 at 5 different stations near or in the Glomma estuary, in the Hvaler archipelago, Norway. The mean level of the sum of the congeners, 1,050 ng/g, found in cod was 3 times higher than the corresponding level found in flounder (361 ng/g). The influences on the variation in PCB levels of sex, season, and distance from the Glomma outlet and waterway were investigated using 1-, 2-, and 3-way ANOVA. The main effects of these factors as well as their possible interactions were considered. An expected decreasing PCB pollution gradient from the mouth of Glomma was found for cod, while PCB levels in flounder seemed to be less dependent on sampling site. However, the sexes in both fish species exhibited a different pattern in their PCB levels. The PCB levels in female cod were significantly affected by the season of sampling, with PCB levels in September/October significantly greater than the corresponding levels in June and November/December. No such effect was found for male cod. In flounder, a significant station effect on the PCB levels was found for females only, and a decreasing PCB pollution gradient was found to be significant. The interactions between the three factors station, season, and sex were different in the two species.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1907123 TI - Response of xenobiotic metabolizing enzymes of rainbow trout (Oncorhynchus mykiss) to the mono-ortho substituted polychlorinated PCB congener 2,3',4,4',5 pentachlorobiphenyl, PCB-118, detected by enzyme activities and immunochemical methods. AB - The mono-ortho-substituted polychlorinated PCB congener 2,3',4,4',5' pentachlorobiphenyl (PCB-118) was administered i.p. (30 mg/kg body weight) to gonadally immature rainbow trout (Oncorhynchus mykiss), of both sexes. In liver microsomes prepared from fish killed 4 days after administration, the cytochrome P450-dependent monooxygenase activities of 7-ethoxyresorufin O-deethylase (EROD), aryl hydrocarbon hydroxylase (AHH), and aldrin epoxidase (AE) were measured. In addition, NADPH-cytochrome c reductase (NCCR) was analyzed, and the content of a specific cytochrome P450 isozyme was determined with Western blotting and an enzyme-linked immunosorbent assay (ELISA) using rabbit anticod P450IA1 IgG. The monooxygenase parameters EROD and AHH were significantly induced to 558 and 268%, respectively, of the corresponding control values, while NCCR and AE activities were not affected. The antibodies to cod P450IA1 recognized a single protein band (Mr = 58,000 D) in the rainbow trout liver microsomes. The ELISA absorbance of this protein in the PCB-118 treated fish was 401% of the corresponding value in the controls. These results demonstrate that PCB-118 is an effective inducer of the subfamily cytochrome P450IA1 in rainbow trout liver microsomes. PMID- 1907125 TI - Human exposure to polychlorinated biphenyls in Greater New Bedford, Massachusetts: a prevalence study. AB - A study was conducted in the community of Greater New Bedford, Massachusetts, from 1984 through 1987 to assess the prevalence of elevated levels of polychlorinated biphenyls (PCBs) in the serum of individuals aged 18 to 64 years who had resided in the area for at least 5 years. Eight hundred and forty subjects were interviewed, examined, and tested in a cross-sectional sample of the towns of Acushnet, Dartmouth, and Fairhaven and the city of New Bedford. Serum PCBs were measured to estimate the extent of human exposure. Because of documented environmental contamination by PCBs in the New Bedford area, and the practice of recreational fishing in the harbor for food, a significant number of persons with elevated serum PCB levels were expected to be identified. Instead, the prevalence of elevated serum PCBs in the sample was found to be typical of "unexposed" urban populations in the United States. Only 1.3% of the subjects had serum PCB levels greater than 30 ppb. The same percentage was observed among males (n = 391) and females (n = 449). The geometric means of PCB levels were 4.3 ppb among males (Range = 0.50-60.9) and 4.2 ppb among females (Range = 0.38-154). We conclude that the prevalence of elevated serum PCBs is low in the population of Greater New Bedford. PMID- 1907127 TI - N-[4-(3H-1,3,4-oxadiazoline-2-thion-5-yl)phenyl]-N'-substituted thioureas: synthesis and antimicrobiological activities. PMID- 1907126 TI - [Effect of the calcium channel blockers on rotation induced by apomorphine and amphetamine in rats lesioned with 6-hydroxydopamine]. AB - We have studied the effects of calcium channel blockers cinarizine, flunarizine, nicardipine, nifedipine, verapamil and diltiazem on the motor anomalies which can be found in rats with unilateral nigrostriated lesion due to 6-OH-DA. All of them reduce rotation induced by apomorphine according to this order: nifedipine greater than nicardipine greater than diltiazem greater than flunarizine greater than verapamil greater than cinarizine. No effects on rotation induced by amphetamine have been observed. Our data suggest that calcium channel blockers cause dopamine receptor blockade but they do not modify the calcium-non-depending releasing of dopamine induced by amphetamine. PMID- 1907129 TI - The treatment of low grade cerebral astrocytomas by radiotherapy in Queensland. AB - The records of 108 adult patients with supratentorial low grade astrocytoma presenting between 1/1/80 and 31/12/87 were examined for the following factors which might affect survival: patient age, extent of surgical resection, site of tumour, tumour grade, radiation field size and radiation dose. Univariate analysis showed that patient age, field size and radiation dose were significant prognostic factors, but with multivariate analysis only patient age and radiation field size were significant independent variables. It is possible that field size is a proxy variable for tumour size. PMID- 1907128 TI - Adjuvant post-operative radiotherapy in rectal cancer: results from the ANZ Bowel Cancer Trial (Protocol 8202). AB - In July 1982 the Gastrointestinal Section of The Clinical Oncological Society of Australia began a multicentre randomized trial to assess the value of post operative pelvic radiotherapy in the local control of stage B and C carcinoma of the rectum. Patients who had undergone a potentially curative resection were randomized either to no further treatment (NO RT) or to pelvic radiotherapy (RT), 45 Gy in 25 fractions (plus a perineal boost of 5 Gy in 2 fractions after abdomino-perineal resection). The trial was prematurely terminated in December 1985 owing to slow accrual after 70 patients had been randomized: 36 patients to RT and 34 patients to NO RT. Two patients in each group were found to be ineligible after randomization and, for a variety of reasons, thirteen patients who were randomized to RT did not receive that treatment. The incidence of post operative complications were comparable in both groups, indicating that radiotherapy produced no additional problems. Radiotherapy-related morbidity comprised mainly diarrhoea (grade 1 = 2/21; grade 2 = 5/21; grade 3 = 0/21; grade 4 = 1/21). There were no deaths due to radiotherapy and only one patient, with grade 4 diarrhoea, failed to complete the prescribed course of radiotherapy. After an average follow-up period of 52 months there were 15 local recurrences, 8 in the RT group and 7 in the NO RT group, giving an actuarial 2 year local recurrence rate of 16%. There was no difference in the time to local recurrence, either by randomization group (p = 0.50) or by actual treatment received (p = 0.91).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1907130 TI - The role of radiotherapy in the control of midbrain tumours. AB - This study examined 37 patients who were referred to the Queensland Radium Institute between 1980 and 1989 with tumours of the midbrain to determine if there were any factors which were associated with an improved prognosis. In those patients in whom histology was available, the grade of the tumour was of importance. High grade tumours had a shorter survival than low grade tumours. There was a dose response effect with increasing survival as the dose increased from less than 45Gy up to 50Gy. There were no deaths beyond two years, implying that two year survival is an indicator of long term survival. PMID- 1907132 TI - Use of membrane vesicles to estimate the numbers of system y+ and system L amino acid transporters in human erythrocytes. AB - We have used equilibrium values for L-leucine and L-lysine uptake by right-side out vesicles to estimate the membrane abundance (sites/cell) of Na(+)-dependent amino acid transport systems L and y+ in human erythrocytes. All of the intravesicular space was accessible to L-leucine, as judged by comparisons with uridine uptake via the equilibrative nucleoside transporter (10(4) sites/cell). In contrast, only 28% of the total intravesicular space was accessible to L lysine uptake via system y+. Since human erythrocyte membranes generate an average of approximately 1000 vesicles/cell, these data provide evidence that system L is a relatively high-abundance membrane transport protein in human erythrocytes, while system y+ is present in smaller amounts (approximately 300 copies/cell). Calculated turnover numbers for L-lysine transport by system y+ at 37 degrees C are 24 s-1 for zero-trans influx and 150 s-1 for equilibrium exchange influx. PMID- 1907131 TI - The isolation and characterization of mutant alleles at a new X-linked locus, mex, affecting NADP(+)-dependent enzymes in Drosophila melanogaster. AB - The isolation and characterization of mutant alleles in a regulatory gene affecting NADP(+)-dependent enzymes are described. The locus, mex, is at position 26.5 +/- 0.74 on the X chromosome of Drosophila melanogaster. The newly isolated mutant allele, mex1, is recessive to either the mex allele found in Oregon-R wild type individuals or that found in the cm v parental stock in which the new mutants were induced. The mex1 mutant allele is associated with statistically significant decreases in malic enzyme (ME) specific activity and ME specific immunologically cross-reacting material (ME-CRM) in newly emerged adult males. During this same developmental stage in males, the NADP(+)-dependent isocitrate dehydrogenase specific activity increases to statistically significant levels. Females of the mex1 mutant strain show statistically significant elevated levels of the pentose phosphate shunt enzymes, glucose-6-phosphate dehydrogenase and 6 phosphogluconate dehydrogenase. Isoelectric focusing and thermolability comparisons of the active ME from mutant and control organisms indicate that the enzyme is the same. Developmental profiles of mex1 and control strains indicate that this mutant allele differentially modulates the levels of ME enzymatic activity and ME-CRM during development. PMID- 1907133 TI - On the reaction of wheat lipoxygenase with arachidonic acid and its oxygenated derivatives. AB - Lipoxygenase was purified from wheat kernels by means of ammonium sulfate precipitation, gel chromatography on Sephadex G-200 and anion exchange chromatography on DEAE-Sephadex A-50. Arachidonic acid was mainly converted by the wheat lipoxygenase to 5D-hydroperoxy-6E,8Z,11Z,14Z-eicosatetraenoic acid (5D8 HPETE) with other HPETE isomers including 8-HPETE being minor products. At higher concentrations of lipoxygenase, multiple oxygenation products such as 5,15 dihydroxyeicosatetraenoic acid (5,15-diHETE) and, to a lower extent, 8,15-diHETE and lipoxin isomers were detected after reduction of the hydroperoxy derivatives primarily formed. Similar results were obtained with 5D8- or 15L8 hydroxyeicosatetraenoic acid as substrate. Moreover, evidence was obtained for leukotriene A4 synthase activity of the wheat lipoxygenase. PMID- 1907134 TI - Flavin-containing monooxygenase: a major detoxifying enzyme for the pyrrolizidine alkaloid senecionine in guinea pig tissues. AB - Evidence based on optimal pH, thermal stability, and enzyme inhibition data suggests that the NADPH-dependent microsomal N-oxidation of the pyrrolizidine alkaloid senecionine is carried out largely by flavin-containing monooxygenase in guinea pig liver, lung, and kidney. In contrast, the hepatic microsomal conversion of senecionine to the pyrrole metabolite (+/-)-6,7-dihydro-7-hydroxy-1 hydroxymethyl-5H-pyrrolizine (DHP) is catalyzed largely by cytochrome P450. However, the rate of senecionine N-oxide formation (detoxication) far exceeded the rate of DHP formation (activation) in guinea pig liver microsomes over a range of pHs (pH 6.8 to 9.8). In guinea pig lung and kidney microsomes, N-oxide was the major metabolite formed from senecionine with little or no production of DHP. The high rate of detoxication coupled with the low level of activation of senecionine in liver, lung, and kidney may help explain the apparent resistance of the guinea pig to intoxication by senecionine and other pyrrolizidine alkaloids. PMID- 1907135 TI - Crystallization and preliminary x-ray diffraction studies of recombinant rabbit interferon-gamma. AB - Two different crystal forms of recombinant rabbit IFN-gamma were obtained under different crystallization conditions. The first, a tetragonal form with space group P43212 or P41212, was obtained through vapor phase equilibration using the sitting drop rods technique with ammonium citrate as the major precipitating agent. The unit cell dimensions of this crystal form are a = b = 82.1 A and C = 116.3 A. These crystals diffract to 2.8 A resolution and contain a dimer in the asymmetric unit. A second crystal form was obtained by the batch method at pH 8.0 using sodium chloride as the precipitating agent. The crystals are hexagonal, space group P6122 or P6522, and with unit cell dimensions of a = b = 58.0 A and c = 169 A. This form contains monomer in the asymmetric unit and diffracts to greater than 2.7 A resolution. Both forms appear to be eminently suitable for further analyses and crystal structure solution. PMID- 1907136 TI - Kinetic determination of talin-actin binding. AB - Smooth muscle talin prepared from chicken gizzard binds to skeletal muscle actin in vitro. The stoichiometry of 1:3 for talin:fluorescent labelled G-actin was confirmed by steady state titration and viscosity measurements under non polymerizing conditions. The binding constant (Kd) of talin and G-actin was determined by continuous fluorescence titration and gave a value of approx 0.3 microM. The association rate constant of talin and fluorescent labelled G-actin of approx 7 x 10(6) M-1 x s-1 was ascertained by the stopped flow method; the dissociation rate constant was calculated at approx 2-3 s-1. PMID- 1907137 TI - Expression of a mouse tyrosinase cDNA in 3T3 Swiss mouse fibroblasts. AB - 3T3 Swiss mouse fibroblast cell lines expressing tyrosinase, the critical enzyme in melanin synthesis, have been established by co-transfection of a mouse tyrosinase cDNA and a G418-resistance gene. Of sixty-three clones isolated, four are brown in colour, presumably due to synthesis of melanin. Expression of both the tyrosine hydroxylase and dopa oxidase activities of tyrosinase by these pigmented clones has been demonstrated directly by enzyme assays. Electron microscopic studies suggest that the brown pigment is located in membrane-bound cytoplasmic vesicles. PMID- 1907138 TI - Carbon dioxide-induced hypoxia causes selective loss of rat brain protein kinase C-gamma. AB - Protein kinase C purified from the brains of rats killed by decapitation contained isozymes -alpha, beta and -gamma, whereas brain from animals killed by CO2-anoxia contained only the -alpha and -beta forms. Immunoblotting experiments established that exposure to CO2 resulted in a selective loss of protein kinase C gamma protein. PMID- 1907139 TI - The effects of beta-mercaptoethanol and sodium dodecyl sulfate on the Humicola insolens beta-glucosidase. AB - Hydrolysis of p-nitrophenyl-beta-D-glucoside by the beta-glucosidase of a thermophilic and cellulolytic fungus, Humicola insolens was stimulated by two fold in the presence of high concentrations of beta-mercaptoethanol. This enzyme did not have any free sulfhydryl groups and high concentrations of beta mercaptoethanol (5% v/v) reduced all of the three disulfide bonds present in the enzyme. In contrast, the hydrolysis of cellobiose and cellulose polymers was inhibited by 50% under the same conditions. Sodium dodecyl sulfate (1% w/v) even in combination with beta-mercaptoethanol did not show any significant effects on this enzyme. These unusual properties suggest that this enzyme may be of significant importance for understanding the structure of the enzyme. PMID- 1907140 TI - Methylparathion, carbaryl and aldrin impact on nitrogen metabolism of prawn, Penaeus indicus. AB - Changes in hepatopancreas, muscle and gill tissue nitrogen metabolic profiles were studied in a penaeid prawn, Penaeus indicus, following its exposure to sublethal concentrations of methylparathion, carbaryl and aldrin. In all the insecticide exposed prawn tissues, Ammonia levels were significantly increased and a shift in the nitrogen metabolism towards the synthesis of urea and glutamine was observed. Inhibition of glutamate oxidation to ammonia and alpha ketoglutarate by glutamate dehydrogenase suggests a mechanism whereby hyperammonemia is reduced by minimizing the addition of further ammonia to the already existing elevated ammonia pool. Increased alanine and aspartate aminotransferases demonstrates the onset of gluconeogenesis. Mechanisms to detoxify the ammonia by enhancing the synthesis of urea and glutamine at the cellular level was observed in the selected tissues pave way for the survivability of prawns in insecticide polluted environs. PMID- 1907141 TI - Histidine decarboxylase measurement in brain by 14CO2 trapping. AB - A method for measuring histidine decarboxylase (HDC) in crude rat brain homogenates was developed by modification of existing 14CO2-trapping methods. The addition of EDTA to tissue homogenates and assay buffer reduced non-enzymatic decarboxylation, and improved assay sensitivity and reliability. Addition of polyethylene glycol (molecular weight 300, PEG300) to the homogenizing buffer increased enzyme stability, permitting storage of crude homogenates. Studies of time course, tissue dilution and blanks showed that up to 8 mg of tissue could be assayed successfully with a 3.5-hr incubation. S-alpha-Fluoromethylhistidine (FMH) and alpha-hydrazinohistidine, specific inhibitors of HDC, induced concentration-dependent reductions of enzyme activity by up to 90%, whereas inhibitors of other decarboxylases had little or no effect. Kinetic studies of the enzyme in crude homogenates yielded Km and Vmax values similar to those found previously with other HDC methods, although a poor fit was found to a single enzyme model. When determined by the new method, the distribution of HDC in seven regions of the rat brain agreed well with previous results. The method is rapid, simple to perform, and requires no specialized equipment other than a scintillation counter. PMID- 1907142 TI - Amine oxidase activities in rat breast cancer induced experimentally with 7,12 dimethylbenz(alpha)anthracene. AB - The activities and distribution of monoamine oxidase (MAO) and semicarbazide sensitive amine oxidase (SSAO) in solid breast tumour induced in the rat by treatment with 7,12-dimethylbenz(alpha)anthracene (DMBA) were studied. The mammary tumours were classified according to anatomopathological criteria into: the benign fibroadenoma (FAD) and the malignant adenocarcinoma (ADC) and infiltrant adenocarcinoma (I-ADC). The proportions of total MAO (15%) and SSAO activities (85%) did not change with malignancy. However, an increasing degree of malignancy was associated with an increase in MAO-A activity and a decrease in MAO-B and SSAO activities. Kinetic constants were calculated for SSAO and for each MAO form separately, using specific substrates. The Km values did not change significantly with the degree of malignancy, but Vmax values for MAO-A increased whereas Vmax for SSAO and MAO-B diminished with malignancy. The dependence of SSAO activity on protein concentration indicated the presence of endogenous reversible inhibitory material in extracts from the more malign tumours. This inhibitor was associated with the microsomal fraction and was not removed by dialysis. It was also present in detergent-solubilized extracts, suggesting that the phenomenon might be due to an association of the enzyme itself producing an inactive species. PMID- 1907143 TI - Rat adult hepatocytes in primary pure and mixed monolayer culture. Comparison of the maintenance of mixed function oxidase and conjugation pathways of drug metabolism. AB - The stabilities of several drug oxidation and conjugation pathways in adult rat hepatocytes were investigated in two systems: a primary pure culture lasting 3 days and a primary mixed culture (hepatocytes co-cultured with epithelial cells) lasting 10 days. The cytochrome P450 content in hepatocytes drastically declined within 48 hr in both culture systems. Cytochrome P450-dependent mixed function oxidase was measured by the O-dealkylation of ethoxyresorufin (EROD) and of pentoxyresorufin (PROD). UPD-glucuronosyl transferase (UDP-GT) activity was measured using 1-naphthol and morphine as substrates. In both culture systems, the activities of enzymes belonging to the 3-methylcholanthrene-inducible family, namely EROD and 1-naphthol UDP-GT, were much better maintained than those of PROD and morphine UDP-GT, which belong to the phenobarbitone-inducible family: in pure cultures, EROD and 1-naphthol UDP-GT activities declined to 60% of initial values within 3 days; in mixed cultures, EROD activity was stable throughout the 10 day culture period, whereas that of 1-naphthol UDP-GT was stable until day 4 but had declined to 70% of the initial value by day 8. In contrast, PROD and morphine UDP GT activities declined to approx. 30% of the initial values within 2 days in both culture systems, and had dropped to approx. 10% of the initial value within 8 days in mixed culture. Reduced glutathione (GSH) levels fluctuated, but remained high throughout culture. GSH conjugation declined to 40% of initial values within 3 days in pure culture, whereas it remained relatively constant in mixed culture. Comparison of these two culture systems therefore showed that although the inclusion of epithelial cells did prolong hepatocyte viability, there was a change in relative enzyme activities in both systems, suggesting a shift towards a more de-differentiated drug metabolism pattern. PMID- 1907144 TI - Effects of hexamethylene bisacetamide on induction of monocytic differentiation of human U-937 myeloid leukemia cells. AB - The present studies have examined the effects of hexamethylene bisacetamide (HMBA) on the human U-937 monocytic cell line. HMBA treatment was associated with: (1) decreases in U-937 cell proliferation, (2) increases in nonspecific esterase activity and cell surface antigen expression consistent with monocytic differentiation, (3) decreases in c-myc gene expression, and (4) induction of tumor necrosis factor (TNF) transcripts. Treatment of U-937 cells with HMBA was also associated with increases in phospholipase A2 activity and increases in the release of arachidonic acid and its metabolites. Dexamethasone, an agent previously shown to inhibit monocytic differentiation, had no detectable effect on the down-regulation of c-myc, but blocked the induction of TNF expression. Taken together, the results demonstrate that HMBA induces monocytic differentiation of U-937 cells and that this effect is sensitive, in part, to dexamethasone. PMID- 1907145 TI - Differential expression and ciprofibrate induction of hepatic UDP glucuronyltransferases for thyroxine and triiodothyronine in Fischer rats. PMID- 1907146 TI - Conjugation of 1-naphthol in the gastric mucosa of guinea pigs. AB - 1-Naphthol was conjugated in tissue pieces of the gastric wall to naphthol glucuronide (85%) and naphthol sulfate (15%). There was no regioselectivity in different parts of the stomach. In separated gastric mucosal cell populations, the activities of both transferases were highest in the mucous cell fraction (apparent Vmax of glucuronidation: 0.83 nmol/mg protein/min; apparent Vmax of sulfation: 0.11) with only little, or no activity in chief cells and parietal cells. Immunohistochemically glucuronosyltransferase 1 was predominantly localized in surface mucous cells. In conclusion, the gastric mucosa is an important organ for phase II biotransformation. PMID- 1907147 TI - Sensitization enhances the adenylyl cyclase responsiveness in alveolar macrophages. Changes induced at post-receptor level. AB - Using membrane fractions (MF) from guinea pig alveolar macrophages (AM), we investigated the effects of sensitization and antigen challenge on the stepwise activation of adenylyl cyclase considering receptor binding, G-protein coupling and direct stimulation of the enzyme. Receptor binding studies, using [125I]ICYP as the beta-adrenoceptor specific ligand, show that neither receptor number (Bmax) nor receptor affinity constants (Kd values) were affected by sensitization or antigen challenge. Using forskolin as a direct stimulant of AC, alterations in the enzymatic activity of AC could be excluded. Pretreatment of the different MF with cholera toxin (CT, a toxin which eliminates GTPase activity) and subsequent stimulation of AC with GTP, shows an increased responsiveness in MF from sensitized and antigen challenged AM. In addition, pretreatment of MF from naive AM with increasing doses of CT results in a maximal AC response at the higher concentrations used (50-100 micrograms/mL), an effect not observed in MF from sensitized and antigen challenged AM. In these MF, the AC response still increases after pretreatment with such doses of CT. These data suggest that the enhanced AC responsiveness in AM, induced by sensitization and antigen challenge, results from alterations in alpha s-subunits. PMID- 1907149 TI - Glucuronidation of 3'-azido-3'-deoxythymidine catalyzed by human liver UDP glucuronosyltransferase. Significance of nucleoside hydrophobicity and inhibition by xenobiotics. AB - The enzymatic glucuronidation of 3'-azido-3'-deoxythymidine (AZT) catalyzed by human liver microsomal UDP-glucuronosyltransferase (EC 2.4.1.17, UDPGT) was inhibited by a number of nucleoside analogs. The inhibitory potency of these nucleoside analogs correlated with their hydrophobicity (r2 = 0.90, N = 13). Since similar results were obtained with solubilized UDPGT (r2 = 0.87, N = 7), the affinity of the nucleosides for UDPGT was probably being assessed rather than the ability of the compounds to access the membrane-bound enzyme. Three homologous inhibitors, 3'-azido-2',3'-dideoxyuridine (AzddU), 5-ethyl-AzddU, and 5-propyl-AzddU, were also studied as substrates of UDPGT. The substrate efficiency (Vmax/Km) of these three compounds and AZT also correlated with their hydrophobicity (r2 = 0.94). Sixteen drugs that are structurally unrelated to nucleosides also inhibited the glucuronidation of AZT. The mechanism of inhibition was competitive for seven compounds tested. Ki values were estimated from Dixon plots for nine other less soluble inhibitors; their mechanism of inhibition was assumed to be competitive. Since the peak physiological drug concentrations of the tested inhibitors are considerably less than their Ki values, none of these compounds are expected to strongly inhibit AZT glucuronidation in humans. However, the rank order of these drugs with respect to their inhibitory potential is probenecid greater than chrloramphenicol greater than naproxen greater than phenylbutazone much greater than other drugs tested. PMID- 1907150 TI - Antihypertensive and haemodynamic properties of the potassium channel activating (-) enantiomer of cromakalim in animal models. AB - The present studies describe the blood pressure lowering, and some other haemodynamic effects, of the potassium channel activator, BRL 38227 ((-) enantiomer of cromakalim, CAS 94470-67-4) in various animal models. BRL 38227 was a potent antihypertensive agent following oral administration to conscious spontaneously hypertensive rats, SHR, (0.038, 0.075 and 0.15 mg/kg), renal hypertensive cats (0.035 and 0.05 mg/kg) and renal hypertensive dogs (0.05 and 0.1 mg/kg). The (+) enantiomer of cromakalim (BRL 38226) was without effect on blood pressure in the conscious rat and cat confirming the stereospecific mode of action of this potassium channel activator. Tachycardia accompanied the antihypertensive effect of BRL 38227 in these models and in the rat this effect could be abolished by pretreatment with atenolol (conscious SHR), diltiazem, verapamil, propranolol and alinidine (anaesthetised rats). In addition to reflex tachycardia, BRL 38227 also increased plasma renin activity and aldosterone levels in the conscious renal hypertensive cat. In both the anaesthetised normotensive cat (0.001 mg/kg/min i.v.) and dog (0.0025 to 0.02 mg/kg i.v.) BRL 38227 lowered blood pressure and total peripheral resistance while increasing cardiac output via increased heart rate and stroke volume in the cat and via increased heart rate alone in the dog. BRL 38227 reduced renal vascular resistance in both conscious (0.01, 0.015 and 0.02 mg/kg p.o.) and anaesthetised (0.001 mg/kg/min i.v.) cats and the effect was maintained despite marked reductions in blood pressure. In the anaesthetised dog, BRL 38227 was a potent coronary arterial dilator and this effect was also maintained in the face of marked blood pressure lowering activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1907151 TI - Hormone replacement therapy prevents coronary artery disease in ovariectomized cholesterol-fed rabbits. AB - The prevention of coronary artery disease in women is of considerable importance. We have therefore investigated the influence of oestrogen monotherapy and oestrogen-progestogen replacement therapy on coronary artery disease using a simple morphometric method. We studied sixty-three cholesterol-fed rabbits for nineteen weeks. They were randomized to either ovariectomy (51 rabbits) or a sham operation (12 rabbits). The ovariectomized rabbits were randomized to receive either 17 beta-estradiol, 17 beta-estradiol plus norethisterone acetate, 17 beta estradiol plus levonorgestrel, or placebo. The rabbits with the sham operation received placebo. The hormone therapies reduced the development of coronary artery disease compared to placebo (p less than 0.0001). Furthermore, the coronary artery disease was attended by atherosclerosis in the more distal parts of the coronary arteries (p less than 0.0001), the thoracic aorta (p less than 0.0001) and the abdominal aorta (p less than 0.0001), and by a reduced relative heart weight (p less than 0.05). We conclude that coronary atherosclerosis can be determined quantitatively by morphometry in rabbit arteries. Estradiol monotherapy reduces coronary atherosclerosis in cholesterol-fed rabbits and the addition of norethisterone acetate or levonorgestrel does not attenuate this beneficial effect. PMID- 1907148 TI - A comparison of the decarbamoylation rates of physostigmine-inhibited plasma and red cell cholinesterases of man with other species. AB - Plasma and red cells from a variety of animal species were used to demonstrate that there is a relationship between the decarbamoylation rates of physostigmine inhibited plasma and red cell cholinesterases in vitro and the effectiveness of carbamate pretreatment against nerve agent poisoning reported in the literature. Decarbamoylation rates were faster in the non-human primates than in the guinea pig, and carbamate pretreatment is more effective in these species than in the guinea-pig. The data for the decarbamoylation rates of physostigmine-inhibited enzymes suggests that the non-human primates are the best animal model for extrapolation of protection studies from animal species to man. Control values for red cell acetylcholinesterase (AChE) activity (mumol/min/mL blood) using acetylthiocholine (1 mM) were higher in the human (4.98) and the rhesus monkey (4.14) than in the marmoset (0.84) and the guinea-pig (0.83). Plasma cholinesterase (ChE) activity (mumol/min/mL plasma) using butyrylthiocholine (10 mM) was highest in the rhesus monkey (9.29), intermediate in human (5.10) and guinea-pig (6.06), and lowest in the marmoset (4.07). There was a species difference in the relative activity of AChE: ChE in blood, human (65:35), rhesus monkey (45:55), marmoset (30:70) and guinea-pig (20:80). The rate of recovery of red cell AChE and plasma ChE activities, following incubation of whole blood with physostigmine (1 x 10(-7) M), was in the order human greater than rhesus monkey greater than marmoset greater than guinea-pig. During the incubation of red cells with physostigmine there was little recovery of AChE activity for 3-4 hr in any species. During the incubation of plasma with physostigmine there was complete recovery of ChE activity by 2-3 hr in the human and rhesus monkey and a significant recovery by 3 hr in the marmoset and guinea-pig. This suggests that a component of plasma, possibly ChE, was responsible for the degradation of physostigmine, presumably by hydrolysis. There was a marked species difference in the decarbamoylation rates of physostigmine-inhibited enzyme. In the red cell the t1/2 values (min) were 14.8 (human), 21.2 (rhesus monkey), 17.9 (marmoset) and 31.9 (guinea-pig). In the plasma the t1/2 values (min) were 11.2 (human), 32.9 (rhesus monkey), 44.1 (marmoset) and 52.4 (guinea-pig). PMID- 1907152 TI - Wernicke's encephalopathy in an autopsy material obtained over a one-year period. AB - In a material comprising 279 consecutive autopsies obtained over a one-year period there were four cases of Wernicke's encephalopathy (WE), of which three were inactive (chronic) and one was active (acute). The latter was not related to chronic alcoholism. Our findings show that WE may be regularly present in a routine autopsy series. In only one case was WE suspected clinically and none of the cases revealed macroscopic brain changes indicative of WE. We therefore suggest that sections of the mammillary bodies should be taken routinely to detect all possible cases of WE. PMID- 1907153 TI - Immunization against serogroup B meningococci. Opsonin response in vaccinees as measured by chemiluminescence. AB - One hundred and thirteen healthy volunteers were immunized twice (six weeks apart) with four different doses (12.5, 25, 50 and 100 micrograms, measured as protein content) of an outer membrane vesicle vaccine from a serogroup B meningococcal strain (44/76, B:15:P1.16) complexed to serogroup C meningococcal polysaccharide and/or Al(OH)3 i.e. 12 different vaccines. Serum opsonic activity against the serogroup B strain was measured using a chemiluminescence method. A significant rise in serum opsonic activity was demonstrated in 84 volunteers (74%) six weeks after the first injection and in 97 (86%) six weeks after the second. All vaccinees with low preimmunization values (less than 25 mVs) experienced a significant increase in opsonic activity. A dose-related response was most evident for the vaccines containing adjuvant, and these vaccines were associated with a maximum response six weeks after the second injection, while the vaccines without Al(OH)3 induced a peak response six weeks after the first injection. The postimmunization opsonic activity was similar to that found in convalescent sera, indicating that the vaccines may protect against serogroup B meningococcal disease. PMID- 1907154 TI - Selective transmission of mitochondrial DNA in heteroplasmic lines for intra- and interspecific combinations in Drosophila melanogaster. AB - The transmission of mitochondrial DNA (mtDNA) was investigated in the heteroplasmic lines of Drosophila melanogaster at 19 degrees C and at 25 degrees C. The selective transmission of one type of mtDNA was dependent on the temperature at which the lines were maintained. In heteroplasmic lines for an intraspecific combination induced by germ-plasm transplantation using D. melanogaster as a germ-plasm donor, the proportion of donor mtDNA decreased in four out of five lines examined, the decreasing rate of which being greater at 25 degrees C than at 19 degrees C. Donor mtDNA was lost by the 20th generation at 25 degrees C. For an interspecific combination using D. mauritiana as a germ-plasm donor, the proportion of donor mtDNA increased and endogenous mtDNA was replaced with donor mtDNA at 25 degrees C. But donor mtDNA was almost lost at 19 degrees C by the 14th generation in all four lines examined. Possible mechanisms involved in the temperature-dependent modes of mtDNA transmission are discussed. PMID- 1907158 TI - Specimen collection for virological tests. PMID- 1907156 TI - Spaceflight: galactic nursing. PMID- 1907157 TI - Childhood arthritis: Still's disease. PMID- 1907159 TI - Nursing models: caring in relation to Orem's theory. PMID- 1907155 TI - Nitrous oxide sedation causes post-hyperventilation apnoea. AB - We have studied, in six normal subjects, the effect of nitrous oxide sedation on the ventilatory pattern and oxygen saturation using pulse oximetry (SpO2) after hyperventilation to an end-tidal carbon dioxide partial pressure (PE'CO2) of 3 kPa. This value of PE'CO2 was shown to be less than the apnoeic threshold of all these subjects when their ventilation vs PE'CO2 response curves were plotted. All subjects became apnoeic when told to relax following hyperventilation while breathing 75% nitrous oxide for 90 s. Apnoea was defined as cessation of breathing for 20 s or more. The mean duration of apnoea was 78 s (range 29-130 s). All subjects demonstrated arterial desaturation (mean SpO2 75%, range 44 87%). In contrast, following hyperventilation with air, no apnoea was seen in any subject, although there was some evidence of desaturation (mean SpO2 92.5%, range 88-98%). It was concluded that subjects who are sedated with nitrous oxide behave similarly to those who are anaesthetized rather than to those who were fully conscious, in that they become apnoeic below the apnoeic threshold point. The reduction in SpO2 after hyperventilation was explained almost entirely by apnoea and may explain abnormalities of respiratory control and hypoxaemia in patients recovering from general anaesthesia or sedation accompanied by hypocapnia. This mechanism may be of importance in obstetric patients after breathing Entonox, when apnoea and hypoxaemia may reduce oxygen delivery to the fetus. PMID- 1907161 TI - The crucial importance of good nurse/client communication. PMID- 1907160 TI - Evaluating primary nursing. Part 2. PMID- 1907162 TI - Tradimus. Further education: bettering one's self? PMID- 1907164 TI - Tradimus. International: getting into a state. PMID- 1907163 TI - Tradimus. International: French connections. PMID- 1907165 TI - Tradimus. Educational innovation: Project Centurion. PMID- 1907166 TI - Tradimus. Communication: the missing link. PMID- 1907167 TI - Tradimus. Just imagine. PMID- 1907168 TI - Tradimus. Nursing class heroes: shake some action. PMID- 1907169 TI - Tradimus. Nursing class heroes: Project 2000 is. PMID- 1907170 TI - Green Paper: consulting on health. Interview by Derek Hand. PMID- 1907171 TI - Me and my teddy bear. PMID- 1907172 TI - Developing countries. Nicaragua: a good example in health. PMID- 1907173 TI - An incontinence helpline service. PMID- 1907174 TI - Chemotherapy-induced hair loss. PMID- 1907175 TI - Computers in nursing: expert systems in nursing. PMID- 1907177 TI - Conversion course for enrolled nurses. PMID- 1907178 TI - Nursing knobbly knees. PMID- 1907179 TI - Multi-faceted ethics. PMID- 1907176 TI - Evaluating primary nursing. Part 3. PMID- 1907180 TI - PREPP: prepared for the worst? PMID- 1907181 TI - Working fathers: man about the house. PMID- 1907182 TI - Nursing development? PMID- 1907183 TI - Coping with infertility. PMID- 1907184 TI - HIV in prison: a double life sentence? PMID- 1907185 TI - A role for nurses in sports injuries. PMID- 1907186 TI - Epidemiology: nuclear power and childhood leukaemia. PMID- 1907187 TI - Staff retention: why nurses leave the profession. Part 1. PMID- 1907188 TI - Mentorship in nurse management. PMID- 1907189 TI - Caring for sick buildings. PMID- 1907190 TI - Quality care: outpatient object lesson. PMID- 1907191 TI - Communication: speak no evil. PMID- 1907192 TI - Working parents: a sick situation. PMID- 1907193 TI - Skill mix: stretching shrinking nurses. PMID- 1907194 TI - Legal notes: Risk-taking: a nurse's duty. PMID- 1907196 TI - Happy birthday sweet 2000. PMID- 1907195 TI - Project 2000 plus one. PMID- 1907197 TI - Urinary leukocyte esterase screening for asymptomatic sexually transmitted disease in adolescent males. AB - The objective of this study was to evaluate the effectiveness of urinary leukocyte esterase on random urine specimens as a screening test for chlamydial and gonococcal urethral infections in asymptomatic males. Random urine specimens were obtained on 106 consecutive asymptomatic adolescent males during intake physical examination at a residential vocational training program. Results of urinary leukocyte esterase were compared to those of urethral cultures for Chlamydia trachomatis and Neisseria gonorrhoeae. Five subjects had positive chlamydia cultures, three subjects had positive gonococcal cultures, and one patient had positive cultures for both organisms. Sixteen subjects had leukocyte esterase tests reported as "trace" or greater. When compare to positive culture results for either Chlamydia or gonorrhea, urinary leukocyte esterase activity had a sensitivity of 78%, specificity of 91%, and positive predictive value of 44%. A random urine specimen for urinary leukocyte esterase activity is a cost effective screening method for chlamydial and gonococcal urethral infections in asymptomatic adolescent males. PMID- 1907198 TI - First catch urine sediment for Chlamydia trachomatis and Neisseria gonorrhoeae culture in adolescent males with pyuria. AB - Traditionally, only symptomatic males or those with a history of exposure are tested for sexually transmitted diseases (STDs). Since urethral infections with Chlamydia trachomatis and Neisseria gonorrhoeae are frequently asymptomatic, a practical, sensitive, and acceptable screening method is desirable. Fifty sexually active males with pyuria (age 13 to 22 years old) diagnosed with 1+ or 2+ leukocyte esterase (LE) dipstick on first catch urine (FCU) were further evaluated by culture of urethral swabs and centrifuged FCU samples for N. gonorrhoeae and C. trachomatis. Eighty-six percent had one or more positive cultures: 17 (34%) N. gonorrhoeae, 18 (36%) C. trachomatis, and 8 (16%) both organisms. FCU culture for N. gonorrhoeae had a 100% sensitivity, specificity, and positive and negative predictive value when compared to urethral swab cultures. FCU culture for C. trachomatis had a 32% sensitivity, 95% specificity, 89% positive predictive value, and a 53% negative predictive value compared to urethral culture. On the basis of the results of this study, one urethral swab can be eliminated when evaluating male adolescents for urethritis by using spun FCU culture for N. gonorrhoeae. Continued efforts should be made to develop optimal tests to detect STDs which are reliable and encourage compliance in this high-risk group. PMID- 1907199 TI - Distribution and purification of aspartate racemase in lactic acid bacteria. AB - The distribution of aspartate racemase (EC 5.1.1.13) in various kinds of bacteria demonstrated that the enzyme occurs in lactic acid bacteria, such as Streptococcus species and Lactobacillus species. The enzyme from Streptococcus thermophilus IAM10064 was more thermostable than that from Streptococcus lactis IAM1198 which contained the enzyme most abundantly among the lactic acid bacteria we examined here. We purified the enzyme about 3400-fold to homogeneity from cell free extract of S. thermophilus, which is composed of two identical subunits with a molecular weight of 28,000 as a homodimer. The enzyme utilizes specifically aspartate as a substrate, but not alanine and glutamate. Maximal reaction velocity was observed at 37 degrees C and around pH 8.0. The sequence of the NH2 terminal amino acids of the enzyme was determined to be Met-Glu-Asn-Phe-Phe-Ser Ile-Leu-Gly-XXX-Met-Gly-Thr-Met-Ala-Thr-Glu-Ser- Phe-. PMID- 1907200 TI - Localization, isolation and properties of three NADPH-dependent aldehyde reducing enzymes from dog kidney. AB - Three kinds of NADPH-dependent aldehyde reducing enzymes were present in the dog kidney. Aldose reductase was located in the inner medulla region and aldehyde reductase in all regions of the renal cortex, outer medulla and inner medulla. In addition, a new reductase designated tentatively as high-Km aldose reductase, which was converted into an aldose reductase-like enzyme, was present in the inner medulla region of the kidney. Aldose reductase, aldehyde reductase and high Km aldose reductase were purified to homogeneity from each region of the dog kidney. The molecular weight of aldose reductase was estimated to be 38,500 by SDS-polyacrylamide gel electrophoresis and the isoelectric point was found to be 5.7 by chromatofocusing. Aldose reductase had activity for aldo-sugars such as D xylose, D-glucose and D-galactose as substrates and utilized both NADPH and NADH as coenzymes. Sulfate ions resulted in over 2-fold activation of aldose reductase. All aldehyde reductases from the three regions had the same properties. The molecular weights and isoelectric points of aldehyde reductases were 40,000 and 6.1, respectively. The aldehyde reductases were inactive for D hexose, utilized only NADPH as coenzyme and were not affected by sulfate ions. High-Km aldose reductase had a molecular weight of 38,500 and an isoelectric point of 5.4. It had activity for aldo-sugars, but showed much higher Km and lower kcat/Km values than aldose reductase. Sulfate ions inhibited high-Km aldose reductase. It was converted into an aldose reductase-like enzyme by incubation in phosphate buffer at pH 7.0. The three kinds of enzymes were strongly inhibited by the known aldose reductase inhibitors. However, aldehyde reductase and high-Km aldose reductase were, in general, less susceptible than aldose reductase. PMID- 1907201 TI - A senescence up-regulated protein: the rat thyroxine-binding globulin (TBG). AB - Thyroxine-binding globulin (TBG), the major carrier of thyroid hormones in human serum, was thought to be absent in most species, including rodents. We demonstrated recently that in fact the rat possesses a TBG gene, virtually non expressed in young adults, but actively transcribed during post-natal development. We now find that the TBG gene is also increasingly re-expressed during senescence. Evidence is presented suggesting that physiologically decreased thyroid hormone levels, characteristic of neonates and of ageing rats, might constitute a common factor inducing up-regulation of TBG in both developmental and ageing processes. Rat TBG is to our knowledge the first biochemical 'positive' (i.e. increasing) marker of non-pathological senescence, expressed at both biosynthetic and bloodstream levels. PMID- 1907202 TI - Activation of human plasma prekallikrein by Pseudomonas aeruginosa elastase in vitro. AB - Human plasma prekallikrein, precursor of the bradykinin-generating enzyme, was activated in a purified system under a near physiological condition (pH 7.8, ionic strength I = 0.14, 37 degrees C) by Pseudomonas aeruginosa elastase which is a tissue-destructive metalloproteinase. Compared with that, Pseudomonas aeruginosa alkaline proteinase poorly activated it with a rate as low as less than one-twentieth of that of elastase. The activation by elastase was blocked with a specific inhibitor of elastase, HONHCOCH(CH2C6H5)CO-Ala-Gly-NH2 (10 microM). Generation of kallikrein-like amidolytic activity was also observed in plasma deficient in Hageman factor by treatment with elastase, but was not in plasma deficient in prekallikrein. The kallikrein-like activity generated in Hageman factor deficient plasma as well as the generation process itself was indeed inhibited by anti-human prekallikrein goat antibody. These results suggest that the pathological activation of the kallikrein-kinin system might occur under certain clinical conditions in pseudomonal infections. PMID- 1907203 TI - Molecular parameters that control the association of low density lipoprotein apo B-100 with chondroitin sulphate. AB - The association of low density lipoprotein (LDL) with proteoglycans of the arterial intima, in particular chondroitin 6-sulphate proteoglycans, may contribute to LDL accumulation during atherogenesis. We studied the interactions of apolipoprotein B-100 (apo B-100) peptide segments and model peptides with chondroitin 6-sulphate. The ability of these peptides to inhibit complex formation between LDL and chondroitin 6-sulphate was used as a measurement of the interaction. Results from earlier studies suggest that surface located segments of apo B-100 are responsible for the interaction of LDL with heparin and chondroitin sulphate-rich arterial proteoglycans. Therefore 16 hydrophilic apo B 100 peptides were selected for studies and synthesized with a peptide synthesizer. These synthetic peptides were 7 to 26 amino acids long. Four of the peptides inhibited the association of LDL with chondroitin 6-sulphate, namely apo B segments 4230-4254, 3359-3377, 3145-3157 and 2106-2121. The 3359-3377 segment was the most efficient. A common feature between the interacting peptides was an excess of positively charged side chains and based on these results we synthesized nine model peptides that shared sequence characteristics with the interacting apo B-100 peptides. Five of these: RSGRKRSGK, RSSRKRSGK, RGGRKRGGK, RSRSRSRSR and RGRGRGRGR were shown to block the LDL-chondroitin-6-sulphate association, RSRSRSRSR being the most effective. The results suggest that the optimal association of the peptides with chondroitin 6-sulphate is obtained with a minimal chain length of nine amino acids and a minimum of five positive charges and that flexibility in the binding region is important. PMID- 1907205 TI - [The effect of DNAse I on bacterial growth depending on the cultivation conditions and on the physiological characteristics of the inoculate]. AB - The stimulating effect of DNAase 1 on Escherichia coli reproduction has been studied depending on the content of slowly growing cells in the inoculation culture in the phase of delayed growth. Three cell fractions of E. coli have been obtained using the stepwise separation of the population in terms of buoyant density in the phase of delayed growth. In contrast to fractions I and II the fraction III contains cells with delayed growth, permeable to exogenous DNAase 1 and sensitive to the action of this enzyme. The faster growth of bacterial cells has been shown to be caused by the direct ferment action on the slowly growing cells. The autometabolites and autolysates don't take part in this process. PMID- 1907204 TI - Transduction of the bradykinin response in human fibroblasts: prolonged elevation of diacylglycerol level and its correlation with protein kinase C activation. AB - Stimulation of quiescent human fibroblasts with the peptide mitogen bradykinin (BK) led to a biphasic elevation in cellular 1,2-diacylglycerol (DAG), as estimated by either measurement of total DAG mass or [3H]arachidonate incorporation. A rapid initial transient that peaked 15 s after BK addition was followed by a decline to near basal levels then a second rise to a plateau phase during which DAG levels remained elevated for less than or equal to 45 min. The source of the initial DAG transient appeared to be primarily polyphosphoinositides as these phospholipids were rapidly hydrolyzed after BK addition. This transient correlates well temporally with previous observations of the kinetics of inositol trisphosphate accumulation and intracellular free [Ca2+] observed in the same cells. Cultures preincubated with [3H]myristic acid incorporated label predominantly into the phosphatidylcholine (PC) pool. Subsequent addition of BK under these conditions caused only a relatively slow accumulation of [3H]DAG to a plateau level, without an initial transient. Together with the observation that PC was found to decrease upon BK stimulation, these observations suggest that the late phase of DAG accumulation may involve breakdown of other phospholipids including PC. To investigate the consequences of DAG elevation we examined the phosphorylation of an acidic 80 kDa protein, whose phosphorylation is solely dependent on the activation of protein kinase C (PK-C). The 80 kDa fibroblast protein could be immunoprecipitated by an antibody to bovine brain "myristoylated and alanine-rich C-kinase substrate" (MARCKS) and phosphopeptide maps of brain and fibroblast MARCKS were similar. Stimulation of [32P]-prelabeled fibroblasts with serum, BK, vasopressin, or 12-O-tetradecanoyl phorbol acetate, but not epidermal growth factor or calcium ionophores, resulted in the rapid phosphorylation of MARCKS. With BK or serum this phosphorylation showed an initial transient peak at less than 1 min then rose again to a plateau level that was sustained for less than or equal to 45 min. Removal of BK resulted in a rapid decline in MARCKS phosphorylation. These studies show that the biphasic DAG signal in BK-stimulated human fibroblasts correlates well with the state of activation of PK-C. However, the persistent activation of PK-C does not appear to require continued high levels of Ca2+. PMID- 1907207 TI - Molecular biology of the Rh antigens. AB - The RBC Rh antigens are of large clinical importance, but until recently have been poorly understood at a molecular level. The Rh polypeptides are a family of nonglycosylated Mr 30- to 32-Kd transmembrane proteins that are core structural components of the Rh antigens and have been purified and partially characterized biochemically. Rh polypeptides are present in RBCs from normal humans and other mammalian species and are probably required for normal membrane integrity, because they appear to be missing from the RBCs of the rare Rhnull individuals that express several membrane defects. The Rh polypeptides contain an exofacial free sulfhydryl that is important for Rh antigenic reactivity and several intracellular sulfhydryls that appear to be palmitylated, but most of the molecule appears to reside between the leaflets of the phospholipid bilayer. The cDNA coding for a 416-amino acid Rh polypeptide was recently isolated but was not found to share sequence homology with any known protein, and Northern analysis indicated that Rh is erythroid specific. The Rh antigens within the native membranes are thought to exist as a complex of Rh polypeptides and multiple other membrane components, including certain Rh-related glycoproteins. While it is thought that this assembly may be important for the Rh antigenic reactivity, the structural basis of this remains to be established. While the physiologic role of Rh is yet to be defined, several clues indicate that it may play a role in the organization of membrane phospholipids or synthesis or membrane expression of various glycoproteins. While our knowledge of Rh is still very incomplete, recent research has significantly advanced the molecular understanding of these important blood group antigens. PMID- 1907208 TI - Pulmonary tuberculosis, human immunodeficiency virus type-1 and malnutrition. AB - In rural Haiti we measured and compared the muscle protein and calorie reserves (anthropometrics) as well as the visceral protein reserves (serum albumin, tuberculin sensitivity) in 56 HIV (human immunodeficiency virus type-1) seropositive and 108 HIV seronegative pulmonary tuberculosis patients. Results in patients were also compared to the results of the same measurements made in 160 age, sex and residence matched HIV seronegative controls without tuberculosis. Tuberculosis patients, regardless of HIV status, had significantly reduced muscle protein and calorie reserves compared to controls. The serum albumin was significantly lower in HIV seropositive tuberculosis patients (21.0 g/l) compared to HIV seronegative tuberculosis patients (26.9 g/l) and the serum albumin in both tuberculosis groups was significantly lower than in controls (41.3 g/l). The lower the serum albumin in the tuberculosis patients the greater the likelihood of a negative tuberculin test. HIV seropositive tuberculosis patients were significantly more likely to be tuberculin negative than HIV seronegative tuberculosis patients. Tuberculosis is associated with significant malnutrition. Worse malnutrition in tuberculosis patients co-infected with HIV suggests that the effect of the two pathogens on nutrition is additive or, alternatively, that tuberculosis patients who are particularly malnourished are at increased risk for HIV. PMID- 1907206 TI - [Patient oriented, prospective comparative study of three different pump systems for artificial enteral nutrition]. AB - In a prospective cross-over study involving 30 patients, three different pump systems for artificial enteral nutrition were compared: the Nutromat, Flexiflo, and Frenta systems. Depending upon the degree of acceptance, a controlled sequence of priority of the pump systems was established. In addition, 12 functions and features of the different systems were scored using a scoring key (scores: +2, +1, +/- 0, -1, -2). The Nutromat was adjudged the best system by 53% of the patients, the Flexiflo system was preferred by 30%, and the Frenta system by 17%, of the patients. In the average overall rating of functions and features, the Nutromat scored 1.3 ("good"), the Flexiflo 0.8 ("satisfactory"), and the Frenta system 0.4 ("adequate"). All in all, more than half the patients assessed the Nutromat as the most pleasant and also best pump system. PMID- 1907209 TI - Characterization of prominent protein antigens from mycobacteria. AB - Detailed analysis of mycobacterial proteins originally identified by their prominent interaction with the host immune system reveals a number of interesting biochemical characteristics. M. tuberculosis antigens with molecular weights of 71, 65 and 12 kilodaltons (kD) belong to highly conserved heat shock protein families. A group of closely related antigens with molecular weights around 30 kD are major secreted antigens which share the ability to bind to fibronectin. Antigens with molecular weights of 38 kD and 19 kD are probably lipoproteins with a role in nutrient transport, while the 23 kD antigen is the superoxide dismutase enzyme of M. tuberculosis. It is anticipated that further studies along these lines will generate information of importance to the understanding of the lifestyle of mycobacteria in vivo and also to the elucidation of immune mechanisms in mycobacterial disease. PMID- 1907210 TI - Disposable end tidal carbon dioxide detectors. PMID- 1907211 TI - Assessment of blood echogenicity as an alternative measure to erythrocyte sedimentation rate. AB - OBJECTIVE: To determine the relation between erythrocyte sedimentation rate and blood echogenicity and whether measurement of erythrocyte sedimentation rate could be replaced by measurement of blood echogenicity in monitoring acute phase reactions. DESIGN: Simultaneous measurement of echogenicity of flowing blood and erythrocyte sedimentation rate in blood samples and comparison of results. SETTING: A radiological department in a university hospital. SUBJECTS: 83 patients with a suspected venous thrombosis and 36 healthy volunteers. MAIN OUTCOME MEASURES: Correlations between the erythrocyte sedimentation rate, packed cell volume, and echogenicity of flowing blood. RESULTS: Blood echogenicity correlated poorly with the packed cell volume, but strongly correlated with the erythrocyte sedimentation rate (when the packed cell volume was within reference limits) (correlation coefficient = 0.73). Blood samples with a greatly raised erythrocyte sedimentation rate were highly echogenic. Only one of the 30 samples with an erythrocyte sedimentation rate below 10 mm in first hour had a higher echogenicity than the least echogenic sample of the 19 with a sedimentation rate above 30 mm in first hour. CONCLUSIONS: Echogenicity of flowing blood correlates with the erythrocyte sedimentation rate and its measurement may compete with conventional methods for evaluating the long term changes in acute phase reactions. Also, it has the added advantage that non-invasive in vivo measurements of blood echogenicity may become possible. PMID- 1907212 TI - Interictal psychopathology in epilepsy. Prevalence and pattern in a Nigerian clinic. AB - An unselected sample of 204 epileptic patients attending a neurological out patient clinic in Abeokuta, Nigeria, was evaluated for psychiatric morbidity using the CIS. Thirty-seven percent emerged as psychiatric cases, almost a third of these being cases of psychosis. Patients with partial seizure of temporal lobe origin were the most psychiatrically impaired, while those with partial seizure of non-temporal lobe origin the least. These findings are broadly similar to those reported for epileptic populations in other studies. However, in spite of the relatively high prevalence of major psychiatric disorders among these patients, their impairments were more likely to remain 'hidden' and untreated than those in similar patients in developed countries. PMID- 1907213 TI - Possible role for G-proteins in behavioral sensitization to cocaine. AB - The role of G-proteins in behavioral sensitization to cocaine was examined by injecting pertussis toxin (PTX) into the A10 dopamine cell group. The capacity of acute cocaine to increase motor activity and dopamine release in the nucleus accumbens was significantly augmented in rats pretreated 14 days earlier with PTX. These data suggest that injection of PTX into the A10 dopamine cell group produces a long-term alteration in mesolimbic dopamine function, and implicates A10 dopamine neurons and G-proteins in the development of behavioral sensitization. PMID- 1907214 TI - Morphological transformation of microglia in vitro. AB - Isolated microglia underwent in vitro morphological transformation to ameboid, rod-shaped and ramified forms in response to several cytokines, factors from astrocytes, or factors which affect macrophage function. These morphological transformations were reversible. Examination of the enzymatic activity, superoxide anion formation and proliferative activity of these transformed microglia indicated that the ameboid forms were activated, rod-shaped microglia were proliferating, and the ramified forms were resting microglia. PMID- 1907215 TI - Responses of the basilar artery to products released by platelets during chronic hypertension. AB - The goal of this study was to determine whether responses of the basilar artery to products released by platelets are altered during chronic hypertension. The diameter of the basilar artery was measured using intravital microscopy in normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) (6 8 months old) in response to adenosine 5'-diphosphate (ADP), serotonin, and the thromboxane analogue, U-46619. Dilatation of the basilar artery in response to nitroglycerin was also examined in WKY and SHR. Topical application of ADP (10 and 100 microM) produced only minimal changes in diameter of the basilar artery in WKY (3 +/- 1% and 1 +/- 1%, respectively) and SHR (-0.5 +/- 2% and -2 +/- 3%, respectively) (P greater than 0.05 vs WKY). Nitroglycerin, however, produced potent vasodilatation in WKY and SHR. Constriction of the basilar artery in response to serotonin was potentiated in SHR compared to WKY. Serotonin (0.1 and 1.0 microM) constricted the basilar artery by 11 +/- 2% and 20 +/- 2%, respectively, in WKY and by 29 +/- 3% and 40 +/- 3%, respectively, in SHR (P less than 0.05 vs WKY). In contrast, the thromboxane analogue (U-46619) (0.1 and 1.0 microM) produced similar constriction of the basilar artery in WKY (13 +/- 1% and 18 +/- 2%, respectively) and in SHR (14 +/- 3% and 21 +/- 6%, respectively). Thus, augmented vasoconstriction during chronic hypertension was specific for serotonin. Next, we examined the role of the cyclooxygenase pathway in responses of the basilar artery to ADP and serotonin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1907216 TI - Further indication that distinct dopaminergic subsets project to the rat cerebral cortex: lack of colocalization with neurotensin in the superficial dopaminergic fields of the anterior cingulate, motor, retrosplenial and visual cortices. AB - The extent of neurotensin (NT) colocalization in the different dopamine (DA) terminal fields of the rat cerebral cortex has been investigated and compared to previous data obtained in man (Gaspar et al., J. Comp. Neurol., 279 (1989) 249 271). Both innervations were revealed with single- or double-labeling immunocytochemical methods. Tyrosine hydroxylase (TH) was used as a specific marker of DA fibers after lesioning the noradrenergic system either with 6 hydroxydopamine (6-OHDA) at birth or DSP4 in adulthood. Three classes of afferents were observed which had a different regional and laminar distribution. First, a dense meshwork of finely dotted NT-positive varicosities occupied restricted areas of the limbic system: the granular retrosplenial and the deep entorhinal cortices and the subicular complex. These NT projections contained no double-labeled fibers and did not correspond to a mixed NT/TH pathway. Secondly, the mixed NT/DA projections identified previously in the prefrontal cortex (Studler et al., Neuropeptides, 11 (1988) 95-100), extended in fact rostrocaudally in layer VI of the whole cerebral cortex and formed small cluster like groupings in layers II-III of the medial and lateral entorhinal cortex. In all these areas, the mixed NT/TH projections constituted approximately half of the DA terminals. Finally, the DA projections to the superficial layers of the anterior cingulate, motor, retrosplenial and visual cortices, were not colocalized with NT. The DA innervation of layers I-III of the rat anterior cingulate cortex displays striking similarities with that observed in the cingulate, primary motor, premotor and supplementary motor cortices in man: highest regional and laminar density of DA afferents and lack of colocalization with NT. It might thus represent a valuable model for understanding the pharmacology of the DA system besides the mixed DA/NT pathway which does not seem to have a counterpart in the human cerebral cortex. By contrast, that part of the NT innervation of the limbic system which is not colocalized with DA in rat, appears to represent the major fraction of the cortical NT innervation in man. PMID- 1907217 TI - Quantitative localization of human brain monoamine oxidase B by large section autoradiography using L-[3H]deprenyl. AB - The distribution of monoamine oxidase B (MAO-B) in the human brain was studied by quantitative autoradiography using L-[3H]deprenyl as a ligand. Two postmortem brains from patients without any known neurological diseases were used in this study. Cryosections of 100 microns thickness were taken on tape/paper and transferred to gelatinized glass plates. The sections were incubated with 10 nM L [3H]deprenyl for 1 h and exposed to a film at 4 degrees C for 4 weeks. The autoradiograms were analyzed by computerized densitometry. High L-[3H]deprenyl binding was observed in caudate nucleus, putamen, cingulate gyrus and insula cortex. Moderate to low binding was seen in globus pallidus, temporal and parietal cortex and in various thalamus nuclei. Occipital cortex showed the lowest binding among the cortex regions and white matter the lowest among all the regions studied. All the regions in case 2 (aged 67) showed higher degree of binding when compared with case 1 (aged 58), which is in agreement with previous results showing an increase in MAO-B activity with age. When the specific binding of L-[3H]deprenyl was plotted against the MAO-B activities estimated biochemically in punches from the same areas, a high positive correlation was found. PMID- 1907218 TI - Propagation of transient Ca2+ increase in sea urchin eggs upon fertilization and its regulation by microinjecting EGTA solution. AB - Upon fertilization, the concentration of intracellular Ca2+ (Cai) in sea urchin eggs increased up to 3 microM when measured with fura-2, a fluorescent Ca indicator and the increase in Cai traversed from the sperm entry point as a wave over the entire egg at the mean propagation velocities of 5.0 microns/sec in C. japonicus egg and 5.3 microns/sec in H. pulcherrimus egg. However, the velocity was not uniform; i.e., it was rapid in the vicinity of the sperm entry point and the opposite point, but slow in the central region of the egg. Microinjecting a Ca-EGTA buffer and an IP3 solution into the C. japonicus egg induced the transient Cai increase more rapidly than that upon fertilization, due perhaps to the diffusion of the injectates. In order to investigate Ca2+ release during Cai increase upon fertilization, EGTA solutions were microinjected into unfertilized or fertilizing eggs. Microinjecting 100 mM EGTA (final concentration of 1 mM) not only suppressed the transient Cai increase, but also reduced the increased Cai rapidly, and never induced egg activation after insemination, whereas 10 mM EGTA (final concentration of 0.1 mM) did not significantly affect the Cai increase or the activation. Ca2+ released upon fertilization was estimated to be 150-170 microM in the egg cytoplasm from the amount of microinjected EGTA and fura-2. It was concluded that although more than 150 microM of Ca2+ was released intracellularly upon fertilization, Cai increased to only a few microM because most of the released Ca2+ was sequestered by intracellular Ca2+ binding substances. PMID- 1907219 TI - Segregation of modified bacteriorhodopsin aggregations in reconstituted vesicle membrane induced by the change of thermodynamical parameters. AB - It was clearly shown that the change in thermodynamical parameters could cause the segregation of membrane protein aggregations in the phospholipid membrane. At first, reconstituted vesicles were prepared with a membrane protein, bacteriorhodopsin and a constituent phospholipid of biomembranes, L-alpha dimyristoyl phosphatidylcholine. When the temperature of the suspension was decreased or the osmotic pressure was increased by adding poly(ethylene glycol) to this vesicle suspension at 23 degrees, the circular dichroism spectra showed a typical band indicating bacteriorhodopsin trimer formation implying their aggregation. This suggests that the aggregation of trimers proceeded by adding poly(ethylene glycol) into vesicle suspension, just as it proceeded by decreasing the temperature. Next, vesicles were prepared with fluorescein isothiocyanate labeled bacteriorhodopsin, photoemissive bacteriorhodopsin and L-alpha dimyristoyl phosphatidylcholine. The excitation energy transfer between the two modified proteins was measured by fluorescence spectroscopy. In this case, however, when poly(ethylene glycol) was added into the suspension, the yield of the excitation energy transfer decreased. This result indicates that modified proteins aggregate separately in a segregated form in the vesicle membrane. PMID- 1907220 TI - Rapid, low-cost, two-step method to screen for urinary schistosomiasis at the district level: the Kilosa experience. AB - The operational and diagnostic performance of a two-step method for the cost effective screening of urinary schistosomiasis was investigated in the Kilosa District of east-central Tanzania. In the first step a simple questionnaire was administered to 15,073 primary schoolchildren by their class teachers over a 4 week period. The answers to the questionnaires had a high negative predictive value for schistosomiasis, and this permitted the safe exclusion of schools where the risk of the disease was low. In the second step, the head-teachers of the 49 high-risk schools and of 26 low-risk schools were instructed on the use of reagent sticks to detect haematuria. Each head-teacher then performed this test on 80 children selected at random in their schools (5750 children were screened within 6 weeks). Crosschecks of the results in 18 schools confirmed the reliability of the head-teachers' testing and their findings were therefore used to prepare an epidemiological map of the district and to arrange for treatment of positive children. This two-step approach relied entirely on the existing school system and permitted screening of a rural district of area 15,000 km2 (population, 350,000) over a 4-month period at a cost of only US$3000. PMID- 1907222 TI - Presence of carcinogenic heterocyclic amines in urine of healthy volunteers eating normal diet, but not of inpatients receiving parenteral alimentation. AB - For estimation of human exposures to carcinogenic heterocyclic amines, the amounts of four compounds, 3-amino-1, 4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P 1), 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2), 2-amino-1-methyl-6 phenylimidazo[4,5-b]pyridine (PhIP) and 2-amino-3,8-dimethylimidazo[4,5 f]quinoxaline (MeIQx), in human urine were measured. Twenty-four hour urine specimens were collected from ten healthy volunteers eating normal diet (five males and five females) and three inpatients (two males and a female) receiving parenteral alimentation, and the levels of the four heterocyclic amines were measured by HPLC after partial purification by treatment with blue cotton and ion exchange column chromatography. Trp-P-1, Trp-P-2, PhIP and MeIQx were detected in the 24 h urine samples of all healthy volunteers at levels of 0.04-1.43 ng, 0.03 0.68 ng, 0.12-1.97 ng and 11-47 ng respectively. As 1.8-4.9% of an oral dose of MeIQx is reported to be excreted unchanged in the urine, the daily exposure of humans to MeIQx was estimated to be 0.2-2.6 micrograms/person. The four heterocyclic amines were not detected in the urine of parenterally fed inpatients. These results indicate that humans are continually exposed to carcinogenic heterocyclic amines in food, and these compounds may not be formed endogenously. PMID- 1907221 TI - Experimental chemotherapy of Trypanosoma cruzi infection: persistence of parasite antigens and positive serology in parasitologically cured mice. AB - Mice infected with Trypanosoma cruzi, but parasitologically cured after specific chemotherapy, continued to exhibit positive indirect immunofluorescence serological tests 3-6 months after the therapy. Treatment of trypanosome antigens with monospecific antisera produced in rabbits, and examination by immunoelectron microscopy following peroxidase labelling disclosed the presence of membrane deposits in cell processes in the spleens of the mice. Similar deposits were observed in the external membranes of T. cruzi amastigotes in the spleens of acutely infected mice, but not in normal control mice. No reaction occurred in tissues not previously treated with the monospecific anti-T. cruzi serum. Positive cells in treated and cured mice, as well as in the not cured or untreated control mice, were located in germinal centres of the splenic white pulp and presented long and branching cytoplasmic processes, which are indicative of dendritic cells of the lymphoid follicles of the spleen. PMID- 1907223 TI - Induction of tumors in the Japanese house musk shrew, Suncus murinus (Insectivora), by dimethylbenz[a]anthracene. AB - The carcinogenic effect of 7,12-dimethylbenz[a]anthracene (DMBA) was examined in the virgin female Japanese house musk shrew, Suncus murinus (family: Soricidae, order: Insectivora). Leukemia, musk gland tumors, pilosebaceous tumors and sarcomas were induced in the DMBA-treated shrews, whereas none of the controls developed any tumors up to 50 weeks of age. DMBA emulsion was administered i.p. at a dose of 1.25 or 2.5 mg once a week, with either four or eight doses being given from 8 weeks of age. Leukemia developed in 100% (9/9), 50% (5/10), 56% (5/9) and 0% (0/10) of the animals treated with a total dose of 20 mg (8 x 2.5 mg), 10 mg (8 x 1.25 mg), 10 mg (4 x 2.5 mg) and 5 mg (4 x 1.25 mg) of DMBA respectively. Leukemia was of the lymphatic and/or mast cell type, and the spleen was the organ invariably involved. A dose-dependent effect of DMBA was not observed for pilosebaceous and musk gland tumors. When 1 mg of DMBA powder was dusted into the subcutaneous tissue at 4 weeks of age, sarcomas developed at the dusted site (69%; 9/13). PMID- 1907224 TI - Stimulatory effect of thapsigargin, a non-TPA-type tumor promoter, on arachidonic acid metabolism in the murine keratinocyte line HEL30 and on epidermal cell proliferation in vivo as compared to the effects of phorbol ester TPA. AB - The effect of thapsigargin (Tg), a non-12-O-tetradecanoylphorbol-13-acetate (TPA) type skin tumor promoter, on arachidonic acid and prostaglandin E2 (PGE2) formation in HEL30 keratinocytes and on epidermal DNA synthesis in vitro and in vivo (mouse skin) was investigated and compared with that of the phorbol ester TPA. On a molar basis Tg was 30-fold more potent in inducing the arachidonic acid/PGE2 release than TPA. Applied together, the two agents showed a strong synergistic action. The response critically depended on the presence of Ca2+ in the extracellular medium. While the TPA-induced release was mediated by protein kinase C (PKC) the Tg-induced release was not. In contrast to TPA (1 microM), which is a stimulator of HEL30 DNA synthesis, Tg (0.1-1 microM) inhibited DNA labeling in vitro due to a pronounced cytotoxic effect. TPA did not exhibit such an effect. In vivo both agents were practically equipotent in inducing epidermal DNA synthesis and hyperplasia with TPA having an approximately 10-fold higher irritating potential than Tg. It is concluded that the hyperplasiogenic and tumor promoting effect of Tg in vivo is due to cytotoxicity causing cell death and regenerative hyperproliferation. Thus, Tg-induced skin tumor promotion seems to resemble tumor promotion by mechanical skin wounding, whereas TPA evokes a more specific, i.e. PKC-mediated response. Since despite these mechanistic differences both agents induce an immediate release of arachidonic acid/PGE2 in keratinocytes, this response may be considered to provide an in vitro parameter for irritancy and tumor promotion. PMID- 1907225 TI - Synergistic enhancement of thyroid tumor induction by 2,4-diaminoanisole sulfate, N,N'-diethylthiourea and 4,4'-thiodianiline in male F344 rats. AB - Three thyroid carcinogens, 2,4-diaminoanisole sulfate (DAAS), N,N' diethylthiourea (DETU) and 4,4'-thiodianiline (TDA), were simultaneously administered in the diet to male F344 rats at one-third the concentration of the reported TD50 levels (610, 200 and 46 p.p.m. respectively) for 52 weeks. The resultant incidence of thyroid adenocarcinomas in the combined treatment group (18/18: 100%) was significantly higher than those in each individual treatment group (DAAS, 0/21; DETU, 1/21; TDA, 2/20). Hepatocellular carcinomas (9/18, 50%) and lung adenomas (6/18, 33%) were also induced by the combined treatment, the incidences being higher than in the TDA group (3/20, 15% and 4/20, 20% respectively) to which these tumors were limited in the three groups treated with single chemicals. Thus, the results indicated that the three carcinogens exert apparent synergism in thyroid carcinogenesis when administered simultaneously. PMID- 1907226 TI - Separation and identification of N4-(guanosin-7-yl)-4-aminoquinoline 1-oxide, a novel nucleic acid adduct of carcinogen 4-nitroquinoline 1-oxide. AB - A novel nucleic acid adduct of the carcinogen 4-nitroquinoline 1-oxide, N4 (guanosin-7-yl)-4-aminoquinoline 1-oxide, was separated and identified after RNA was treated with activated 4-hydroxyaminoquinoline 1-oxide. This is the first report of a 7-arylaminated guanine adduct produced by arylaminating carcinogens. PMID- 1907227 TI - Arachidonic acid elicits endothelium-dependent release from the rabbit aorta of a constrictor prostanoid resembling prostaglandin endoperoxides. AB - This study was designed to investigate the mediator(s) of endothelium-dependent arterial constrictor responses evoked by arachidonic acid in vitro. A segment of descending rabbit thoracic aorta was isolated and perfused (1-2 ml/min) with oxygenated Krebs' bicarbonate buffer. Changes in the vascular smooth muscle contracting activity of the aortic effluent were detected by superfusion bioassay using either strips of rabbit aorta or rings of dog saphenous vein, both denuded of endothelium and exposed to indomethacin (10 microM). Arachidonic acid (5-50 micrograms) injected into the inflow of the perfused aorta caused a dose-related increase in the vascular smooth muscle-contracting activity of the aortic effluent, whereas arachidonic acid added directly into the aortic effluent did not. The arachidonic acid-induced elevation of vascular smooth muscle-contracting activity in the aortic effluent was not apparent when indomethacin (10 microM) was added to the aortic inflow to inhibit cyclooxygenase, when the endothelium of the perfused aorta was removed by rubbing, or when the thromboxane A2/prostaglandin H2 receptors of the vascular tissues used for bioassay were blocked with an antagonist (1 microM SQ29548), and was unaffected when an inhibitor of thromboxane synthase (10 microM CGS 13080) was added to the aortic inflow. This effect of arachidonic acid was accompanied by release of prostaglandin H2 (measured as prostaglandin F2 alpha after reduction with SnCl2) in amounts sufficient to elicit contraction of the vascular tissues used for bioassay and was attenuated when a reducing agent (2 mM FeCl2) that converts prostaglandin H2 to 12-heptadecatrienoic acid was added to the aortic effluent. Collectively, these observations suggest that arachidonic acid stimulates endothelium-dependent release from the perfused aorta of a prostanoid that contracts vascular smooth muscle via interaction with thromboxane A2/prostaglandin H2 receptors. The study also suggests that the prostanoid responsible for the vascular smooth muscle-contracting activity of the aortic effluent is a prostaglandin endoperoxide(s) rather than thromboxane A2. PMID- 1907229 TI - Respiratory and circulatory analysis of CO2 output during exercise in chronic heart failure. AB - BACKGROUND: The output of carbon dioxide (VCO2) is controlled by both hemodynamics and ventilation. To understand VCO2 in patients who have chronic heart failure (CHF), we studied 14 patients who had New York Heart Association functional class III failure by measurements of hemodynamics, ventilation, and arterial and venous blood gases at rest and at 50 W of cycle ergometry exercise. METHODS AND RESULTS: Fick principle analysis of VCO2 showed that because of a limited increase in cardiac output, CHF patients widened their venoarterial CO2 content difference from 4.9 +/- 3.5 ml/dl at rest to 11.1 +/- 4.0 ml/dl with exercise (p less than 0.05). This increase in CO2 content difference was achieved with no change in venous CO2 content (from 54.3 +/- 3.3 ml/dl at rest to 54.5 +/- 4.8 ml/dl at exercise, p = NS); however, there was a decrease of arterial CO2 content (from 49.4 +/- 3.7 ml/dl at rest to 43.4 +/- 2.3 ml/dl with exercise, p less than 0.05). Modeling of the CO2 tension-content relation showed that there would have been a small, nonproportional increase of venous CO2 content as venous CO2 tension increased from 43.2 +/- 1.8 mm Hg at rest to 55.3 +/- 4.2 mm Hg during exercise (p less than 0.05); however, the development of metabolic acidosis during exercise entirely blunted the increase of CO2 content. In contrast, both the shape of the tension-content relation and the acidosis of exercise further influenced the decrease of arterial CO2 content as arterial CO2 tension decreased from 37.0 +/- 2.9 mm Hg at rest to 32.0 +/- 3.4 mm Hg during exercise (p less than 0.05) as a result of excess ventilation. CONCLUSIONS: In CHF patients during exercise, the circulatory limitations imposed by a low cardiac output on VCO2 are compensated by a widened venoarterial CO2 content difference. The content difference is not widened through an increase of venous CO2 content but rather by a decrease of arterial CO2 content caused by arterial hypocapnia and metabolic acidosis. PMID- 1907228 TI - A prospective, randomized trial comparing combination half-dose tissue-type plasminogen activator and streptokinase with full-dose tissue-type plasminogen activator. Kentucky Acute Myocardial Infarction Trial (KAMIT) Group. AB - BACKGROUND: The potential benefits of combination thrombolytic agents in the treatment of myocardial infarction remain uncertain. In a small pilot study, we demonstrated that combining half-dose tissue-type plasminogen activator (t-PA) with streptokinase (SK) achieved a high rate of infarct vessel patency and a low rate of reocclusion at half the cost of full-dose t-PA. METHODS AND RESULTS: We designed a prospective trial in which 216 patients were randomized within 6 hours of myocardial infarction to receive either the combination of half-dose (50 mg) t PA with streptokinase (1.5 MU) during 1 hour or to the conventional dose of t-PA (100 mg) during 3 hours. Acute patency was determined by angiography at 90 minutes, and angioplasty was reserved for failed thrombolysis. Heparin and aspirin regimens were maintained until follow-up catheterization at day 7. Acute patency was significantly greater after t-PA/SK (79%) than with t-PA alone (64%, p less than 0.05). After angioplasty for failed thrombolysis, acute patency increased to 96% in both groups. Marked depletion of serum fibrinogen levels occurred after t-PA/SK compared with t-PA alone at 4 hours (37 +/- 36 versus 199 +/- 66 mg/dl, p less than 0.0001) and persisted 24 hours after therapy (153 +/- 66 versus 252 +/- 75 mg/dl, p less than 0.0001). Reocclusion (3% versus 10%, p = 0.06), reinfarction (0% versus 4%, p less than 0.05), and need for emergency bypass surgery (1% versus 6%, p = 0.05) tended to be less in the t-PA/SK group. Greater myocardial salvage was apparent in the t-PA/SK group as assessed by infarct zone function at day 7 (-1.9 SD/chord versus -2.3 SD/chord after t-PA alone, p less than 0.05). In-hospital mortality (6% versus 4%) and serious bleeding (12% versus 11%) were similar between the two groups. CONCLUSIONS: These results suggest that a less expensive regimen of half-dose t-PA with SK yields superior 90-minute patency and left ventricular function and a trend toward reduced reocclusion compared with the conventional dose of t-PA. PMID- 1907230 TI - Cutis laxa: autosomal dominant inheritance in five generations. AB - Cutis laxa is described in three cases: a 17-year-old man, his mother and his maternal grandmother. The onset of skin symptoms occurred from puberty to early adulthood. The skin was loose-hanging, wrinkled and without elasticity. X-ray examination showed numerous gastrointestinal diverticulae in the two older patients, and both had been operated on for abdominal hernia and genital prolapse. There were no cardiopulmonary symptoms. Histopathological investigation showed a reduction in the amount of elastic tissue in the dermis, but normally localized and ultrastructurally normal components. The family history revealed clinically similar cases in at least five generations, consistent with autosomal dominant inheritance. PMID- 1907231 TI - HIV-p24-antigen-bearing macrophages are only present in brains of HIV seropositive patients with AIDS-encephalopathy. AB - The central nervous system of HIV-seropositive patients with and without AIDS encephalopathy was investigated by immunocytochemistry using the monoclonal antibody to the HIV-1 p24 core protein. Numerous p24-immunopositive mono- and multinucleated macrophages could only be detected in patients with typical histological pictures of an AIDS-encephalopathy. These findings allow the supposition that AIDS-dementia is a result of a relatively late infiltration of HIV-infected macrophages from the bloodstream into the brain and is not due to an impairment of neuronal and/or glial cells infected by HIV during the early stage of the disease. PMID- 1907232 TI - Spontaneous bacterial peritonitis due to Neisseria meningitidis serogroup Z in an infant with liver failure. PMID- 1907233 TI - Effect of anti-sensitive toothpastes on opened dentinal tubules and on two dentin bonded resins. AB - Treatment of dentin hypersensitivity will become of increasing importance in the daily practice of dentistry. The goal of any therapy should be the closure of opened dentinal tubules. The present study made an SEM evaluation of the effect of anti-sensitive toothpastes on root dentin with regard to the superficial changes and possible penetration by toothpaste particles. Further, the study performed an evaluation of the wear-resistance of two dentin-bonded resins during brushing, using the same anti-sensitive toothpastes. Having induced coverage of the dentinal tubules with the toothpastes (Sensodyne, Emoform and Macleans Sensitive), no particles were found within the tubules. The application of dentin bonded resins seems an alternative solution for treating dentin hypersensitivity. PMID- 1907234 TI - Pharmacokinetics and pharmacodynamics of glyburide in young and elderly nondiabetic adults. AB - The pharmacokinetics and pharmacodynamics of glyburide were studied in elderly and young nondiabetic adults. Healthy nondiabetic men and women 18-40 years of age (young subjects) and 60-85 years of age (elderly subjects) were recruited. After an overnight fast, the subjects were given a baseline glucose tolerance test (GTT). The next day, again after a fast, each subject was given a 5-mg oral tablet of glyburide, and the GTT was performed one hour later. Serum glucose, serum insulin, and plasma glyburide concentrations were determined. Twenty elderly (mean +/- S.D. age, 65.7 +/- 5.3 years) male (n = 10) and female (n = 10) volunteers and 15 young (22.3 +/- 4.5 years) male volunteers were enrolled. Compared with the young subjects, the elderly subjects had slower glyburide absorption, as determined from a lower peak plasma concentration and smaller area under the plasma concentration-time curve from zero to four hours (AUC0-4). The elderly subjects also had a lower glyburide elimination rate constant and higher volume of distribution and a 52% higher free fraction. There was no difference in the glyburide AUC0-24 or AUC0-infinity or in oral clearance between the groups. The elderly group had greater increases in serum glucose and insulin concentrations after the baseline GTT. After glyburide administration, the elderly group had a smaller fractional decrease in the glucose AUC0-3 from the baseline GTT result than the young subjects. Linear regression analysis of the relationship between the fractional change in glucose concentration and the glyburide AUC0-4 showed significantly different slopes between the two groups. The aging process appears to affect the pharmacokinetics and pharmacodynamics of glyburide. PMID- 1907235 TI - Intermittent flow expiratory ventilation: new technique of limited excursion pulmonary ventilation. PMID- 1907237 TI - [Hair zinc and copper concentration in patients with epilepsy]. AB - The concentration of zinc and copper in the hair of 55 patients with epilepsy was determined. The hair copper levels in patients with epilepsy were significantly lower than those in the normal control group (P less than 0.001). The hair zinc levels in female patients were significantly lower than those in the normal control group (P less than 0.05). In the following patients: (1) with generalized seizure, (2) with the disease course 0-5 years, (3) EEG showed heavy or middle abnormality, (4) had epileptic attacks within one year before the sample was taken, the zinc levels were also significantly lower compared with controls (P less than 0.05). Antiepileptic drugs had more effect on hair zinc than on copper. The increase in the hair zinc and copper and zinc: copper ratio seems to show the efficiency of drugs. PMID- 1907236 TI - Differential mechanisms governing segregation of a univalent in oocytes and spermatocytes of Drosophila melanogaster. AB - In tricomplex heterozygotes in Drosophila melanogaster three metacentric autosomes (the TRI chromosomes) appear as a trivalent in meiosis while one autosome consisting of two homologous arms attached to the same centromere (a compound) behaves as an obligatory univalent. Cytological analysis of meiosis of tri-complex heterozygotes indicates that in oocytes the univalent compound behaves non-independently in relation to segregation of the trivalent. The compound is distributed preferentially to the same pole as one TRI chromosome. In spermatocytes the compound is distributed at random. In some oocytes the directed segregation is shown to be due to a disjunctional interaction between the compound and one partner of the trivalent at the same time as the other two chromosomes of the trivalent are separating from each other. The basic difference between the segregational mechanisms in the two sexes is discussed with a review of evidence indicating that in males segregation is determined by physical linkage that produces a stable orientation of the homologues at metaphase I. On the other hand, both genetic and cytological evidence indicate that in females a physical linkage (a chiasma) is non-essential for maintenance of co-orientation and stability after the onset of prometaphase. Genetic and cytological evidence support the hypothesis that disjunction is predetermined by non-random arrangement of the centromeric regions of chromosomes in the chromocentre - a suprachromosomal organization characteristic of maturing oocytes. PMID- 1907238 TI - [A population-based study on types of viral hepatitis]. AB - The epidemiological features of various types of acute viral hepatitis in 5 regions of Sichuan Province (211,639 population) from Feb. 16, 1987 to Feb. 15, 1988 were studied. The results of the study showed that the incidence of acute viral hepatitis was 167.74 per 100,000 and the proportion of HA, HB, NANBH, HEB, HCM, MIXED infection in all the patients was 24.51%, 38.31%, 24.51%, 3.38%, 3.38%, and 5.92 respectively. There was an incidence of 14.93% for multiple infections. Large incidence differences in these regions (from 110.30 per 100,000 to 299.95 per 100,000) were noted. The sex ratio (male: female) for acute viral hepatitis was 1.75:1. There was a peak attack rate of HA in 0-19 age group. The incidence of HB in 20-39 age group was obviously higher than those in other age groups. For NANBH, attack rate was relatively high in 5-19 age groups. There were no significant age-differences for HEB, HCM and mixed infections. PMID- 1907239 TI - [Ocular histopathology and ultrastructure in mucopolysaccharidosis-I]. AB - The ocular histopathology of type I mucopolysaccharidosis was studied with histochemical, ultrahistochemical, and ultrastructural techniques. The latter method showed extensive intracellular accumulation of fibrillogranular vacuoles in virtually every ocular tissue. Ultra-histochemistry proved that the fibrillogranular material was acid mucopolysaccharide. The pathologic mechanism of scleral thickening, retinal pigment epithelial degeneration, and glaucoma were discussed. PMID- 1907240 TI - [Monoclonal gammopathy]. PMID- 1907242 TI - Metaraminol-induced reversal of acute myocardial ischaemia associated with hypotension and refractory to intravenous nitroglycerin. AB - In seven patients, acute myocardial ischaemia associated with ST segment elevation (5.7 +/- 1.6 mm, mean +/- SEM) and arterial hypotension (systolic blood pressure 57 +/- 9 mmHg), was reversed within 9 min (mean time to reversal 274 +/- 45 s) by the intravenous administration of metaraminol (1.9 +/- 0.2 mg). This myocardial ischaemia was refractory to nitroglycerin and, in every patient, the increases in blood pressure induced by metaraminol (to a mean systolic blood pressure of 191 +/- 22 mmHg) preceded reversal of the ECG changes. It is suggested that, in some patients, transmural myocardial ischaemia of recent onset associated with hypotension can be reversed by transiently increasing blood pressure with metaraminol. PMID- 1907241 TI - Cost-utility analysis of thrombolytic therapy. AB - An analysis of the cost-effectiveness of thrombolytic therapy was performed, based on 3- to 5-year follow-up data, from 533 patients randomized to receive conventional therapy or intracoronary streptokinase. At the 3-year follow-up, mortality was 22% in the former group and 14% after thrombolysis. The estimated average gain in life years by thrombolytic therapy was 3.4, whereas this figure was only 1.6 years in patients with inferior wall infarction, and 5.1 years in patients with anterior wall infarction. The lifetime costs for conventional therapy, estimated as ECU 15,110, were increased by ECU 5530 when thrombolytic therapy was applied, including direct treatment costs and the additional costs of extra coronary bypass surgery and PTCA. After correction for quality of life, and discounting future costs and future events at 5% year-1, the additional costs for each life year were ECU 2940 for all patients treated. This was broken down into ECU 7030 and ECU 2000 for patients with inferior and anterior wall infarction respectively. These figures compare favourably with other modes of cardiovascular therapy. Thrombolytic therapy does not substantially increase the need for bypass surgery or PTCA. It is very cost-effective, and its application should not be limited by economic resources. PMID- 1907243 TI - Effects of intracoronary nitroglycerin on lumen diameter during early follow-up angiography after coronary excimer laser atherectomy. AB - The incidence of coronary vasospasm during and following excimer laser atherectomy is considerable. The aim of this study was to investigate vasoconstriction of the target vessel during early follow-up angiography. In 50 patients an angiogram was performed 24 hours after intervention. Nineteen patients were treated with stand-alone laser atherectomy (group I), another 19 with laser and additional balloon angioplasty (group II) and 12 with balloon angioplasty alone (group III). Lumen diameter and percent stenosis before and after intracoronary application of 0.1 mg nitroglycerin were determined. The differences were compared between groups I, II and III, and for patients with (N = 14) and without (N = 24) vasospasm during laser atherectomy. There was a significant increase in lumen diameter, of 0.17 +/- 0.28 mm, after nitroglycerin in group I, of 0.18 +/- 0.29 mm in group II (P = 0.02) and of 0.03 +/- 0.21 mm in group III (ns). In patients with vasospasm during laser atherectomy the average increase in lumen diameter was 0.28 +/- 0.24 mm (P less than 0.01), and in patients without vasospasm 0.12 +/- 0.29 mm (P = 0.09). We conclude that one day after coronary excimer laser atherectomy intracoronary nitroglycerin significantly affects lumen diameter at the site of previous stenosis, an effect undetectable after balloon angioplasty. Thus, vasoconstriction after excimer laser ablation seems to be a common phenomenon and is prolonged in patients with vasospasm during the previous intervention. PMID- 1907245 TI - Affordable health insurance. PMID- 1907244 TI - [The effect of glibenclamide on the spontaneous evolution of genetically determined diabetes mellitus in C57BL/KsJY db+/+db mice]. AB - The study was carried out on 25 mice of the mutant C57BL/KsJY line carrying the autosomal-recessive gene db (diabetes) in the homozygous state with basal normo- and hyperglycemia by the beginning of the treatment with glybenclamide (the latent and manifest stages of insulin-independent diabetes mellitus). It was found that long-term oral administration of the drug in the therapeutic dose (20 micrograms per mice a day for 3-3.5 months) enhanced the genetically determined disturbances of glucose homeostasis and the insulin-producing apparatus of the pancreas irrespective of the stage of spontaneous diabetes genesis. The development of the organ-specific autoimmune reactions directed to antigens of the pancreatic islands was found. PMID- 1907246 TI - Role of glycation in modification of lens crystallins in diabetic and nondiabetic senile cataracts. AB - To assess the significance of glycation, nonenzymatic browning, and oxidation of lens crystallins in cataract formation in elderly diabetic patients, we measured three distinct products of glycation, browning, and oxidation reactions in cataractous lens crystallins from 29 diabetic patients (mean +/- SD age 72.8 +/- 8.8 yr) and 24 nondiabetic patients (age 73.5 +/- 8.3 yr). Compounds measured included 1) fructoselysine (FL), the first stable product of glycation; 2) pentosidine, a fluorescent, carbohydrate-derived protein cross-link between lysine and arginine residues formed during nonenzymatic browning; and 3) N epsilon-(carboxymethyl)lysine (CML), a product of autoxidation of sugar adducts to protein. In diabetic compared with nondiabetic patients, there were significant increases (P less than 0.001) in HbA1 (10.2 +/- 3.1 vs. 7.1 +/- 0.7%), FL (7.6 +/- 5.4 vs. 1.7 +/- 1.2 mmol/mol lysine), and pentosidine (6.3 +/- 2.8 vs. 3.8 +/- 1.9 mumol/mol lysine). The disproportionate elevation of FL compared with HbA1 suggests a breakdown in the lens barrier to glucose in diabetes, whereas the increase in pentosidine is indicative of accelerated nonenzymatic browning of diabetic lens crystallins. CML levels were similar in the two groups (7.1 +/- 2.4 vs. 6.8 +/- 3.0 mmol/mol lysine), providing no evidence for increased oxidative stress in the diabetic cataract. Thus, although the modification of lens crystallins by autoxidation reactions was not increased in diabetes, the increase in glycation and nonenzymatic browning suggests that these processes may acclerate the development of cataracts in diabetic patients. PMID- 1907247 TI - Tissue-specific effects of aldose reductase inhibition on fluorescence and cross linking of extracellular matrix in chronic galactosemia. Relationship to pentosidine cross-links. AB - Chronic experimental hyperglycemia mediated by galactose has been shown to induce browning and cross-linking of rat tail tendon collagen that could be duplicated in vitro by nonenzymatic galactosylation. To investigate the nature of these changes, Sprague-Dawley rats were placed on a 33% galactose diet without and with sorbinil for 6 and 12 mo. Collagen-linked fluorescence and pentosidine cross links increased with age and galactosemia in tail tendons (P less than 0.001) and skin but were essentially unresponsive to aldose reductase inhibition (ARI). In contrast, tendon breaking time in urea, a likely parameter of cross-linking, was markedly improved (P less than 0.001) by ARI. Fluorescence that was inhibited by sorbinil treatment was increased in pepsin and proteinase K digest of aortic tissue from galactosemic rats (P less than 0.001), but impaired enzymatic digestibility was not observed. Systolic blood pressure as potential consequence of aortic stiffening was not increased in galactosemia. These data suggest that fluorescence in skin and tendon might be in part due to advanced glycosylation and pentosidine formation because these were not decreased by ARI. However, they also suggest that nonfluorescent cross-links may also be forming because, in contrast to fluorescence, tail tendon breaking time was partly corrected by ARI. Thus, it appears that extracellular matrix changes in chronic galactosemia are complex, being partly attributable to advanced glycosylation and partly to polyol pathway activation. PMID- 1907248 TI - Ca(2+)-calmodulin-dependent phosphorylation of islet secretory granule proteins. AB - The effect of Ca2+ and calmodulin on phosphorylation of islet secretory granule proteins was studied. Secretory granules were incubated in a phosphorylation reaction mixture containing [32P]ATP and test reagents. The 32P-labeled proteins were resolved by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the 32P content was visualized by autoradiography, and the relative intensities of specific bands were quantitated. When the reaction mixture contained EGTA and no added Ca2+, 32P was incorporated into two proteins with molecular weights of 45,000 and 13,000. When 10(-4) M Ca2+ was added without EGTA, two additional proteins (58,000 and 48,000 Mr) were phosphorylated, and the 13,000-Mr protein was absent. The addition of 2.4 microM calmodulin markedly enhanced the phosphorylation of the 58,000- and 48,000-Mr proteins and resulted in the phosphorylation of a major protein whose molecular weight (64,000 Mr) is identical to that of one of the calmodulin binding proteins located on the granule surface. Calmodulin had no effect on phosphorylation in the absence of Ca2+ but was effective in the presence of calcium between 10 nM and 50 microM. Trifluoperazine and calmidazolium, calmodulin antagonists, produced a dose dependent inhibition of the calmodulin effect. 12-O-tetradecanoylphorbol 13 acetate, a phorbol ester that activates protein kinase C, produced no increase in phosphorylation, and 1-(5-isoquinoline sulfonyl)-2-methyl piperazine dihydrochloride, an inhibitor of protein kinase C, had no effect. These results indicate that Ca(2+)-calmodulin-dependent protein kinases and endogenous substrates are present in islet secretory granules. PMID- 1907249 TI - Inhibition of diabetes-associated complications by nucleophilic compounds. AB - Mono- and diaminoguanidine inhibited ambient glucose-induced glycosylated end product formation of albumin and collagen 125I-labeled albumin covalent binding in vitro. Diaminoguanidine was a stronger inhibitor than monoaminoguanidine. These compounds also inhibited rat eye lens aldose reductase activity in vitro noncompetitively with respect to NADPH with Ki = 30.6 mM for monoaminoguanidine and Ki = 12.5 mM for diaminoguanidine. When administered daily for 98 days at a dose of 25 mg/kg body wt i.p., both compounds lowered eye lens sorbitol and aldose reductase activity in normoglycemic and alloxan-induced diabetic rats. Again, diaminoguanidine was a better inhibitor. Daily long-term administration of mono- and diaminoguanidine (25 mg/kg body wt i.p.) inhibited and prevented experimental diabetes-induced lens opacity in rats, respectively. It appears that diaminoguanidine has a better therapeutic potential in controlling diabetic complications. PMID- 1907250 TI - von Willebrand factor and development of diabetic nephropathy in IDDM. AB - We tested the hypothesis that dysfunction of vascular endothelium, indicated by an increase in plasma level of von Willebrand factor (vWF), is present in patients with insulin-dependent diabetes mellitus (IDDM) who develop diabetic nephropathy (DN). DN was classified as absent (urinary albumin excretion [UAE] rate less than 15 microgram/min), incipient (UAE rate 15-200 micrograms/min), or clinical (UAE rate greater than 200 micrograms/min). We followed a cohort of 59 patients for a median of 3 yr. At baseline, 52 patients had no DN, 6 had incipient DN, and 1 had clinical DN. At follow-up, 38 patients had no DN (group 1). Incipient DN had developed in 14 patients and worsened in 3 patients. Clinical DN had worsened in 1 patient. Together, these 18 patients comprised group 2. A decrease in UAE was observed in the remaining three patients with incipient DN at baseline (group 3). In group 1, vWF--measured by immunoelectrophoresis and expressed as a percentage of normal--increased slightly (median 10%, range -43 to 145, P = 0.009). In group 2, vWF increased in all patients (median 80%, range 14 to 206 [corrected], P = 0.0002 vs. baseline and group 1). In group 3, vWF decreased (median -19%, range -44 to -18). After correction for possible confounders, i.e., age, varying duration of follow-up, and initial level of vWF, the difference in vWF change between groups 1 and 2 remained significant (P = 0.009). Poor glycemic control at baseline, estimated by glycosylated hemoglobin, was a significant predictor of increases in vWF in both group 1 and groups 1 and 2 combined.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1907251 TI - [The role of serum proteins in maintaining human calcium homeostasis]. PMID- 1907253 TI - Elevation of serum interleukin-6 concentration precedes acute-phase response and reflects severity in acute pancreatitis. AB - Experimental studies have shown that interleukin-6 induces all major acute-phase proteins in the liver, including C-reactive protein. In 50 patients with acute pancreatitis, the serum concentrations of interleukin-6 and C-reactive protein were determined daily during the first week of hospitalization. Patients were divided into three groups according to clinical criteria: mild pancreatitis (less than or equal to 1 complication; n = 25), severe pancreatitis (greater than or equal to 2 complications; n = 15), and lethal outcome (n = 10). Patients with mild disease showed initially slightly elevated levels of interleukin-6 (22.0 +/- 9.8 U/mL) that decreased to low levels within 4 days (5.0 +/- 1.0 U/mL). In patients with severe pancreatitis, serum concentrations of interleukin-6 were initially clearly elevated (35.0 +/- 7.5 U/mL) and remained slightly elevated until day 7 (13.0 +/- 2.0 U/mL). Patients with lethal outcome had markedly elevated initial interleukin-6 concentrations (61.0 +/- 15.0 U/mL) that decreased but were still elevated at day 7 (26.0 +/- 2.5 U/mL). In all three groups, C reactive protein concentrations followed the course of interleukin-6 concentrations by 1 day. There was a positive correlation between maximal interleukin 6 concentrations and maximal increases in the serum concentrations of C-reactive protein (r = 0.66). At days 1 and 2, increased (greater than 15 U/mL) interleukin-6 concentrations (positive predictive value, 91%; negative predictive value, 82%) predicted a severe or lethal course of the disease more accurately than elevated [greater than 0.10 g/L (greater than 10 mg/dL)] C-reactive protein concentrations (positive predictive value, 67%; negative predictive value, 79%). In conclusion, elevated serum concentrations of interleukin-6 followed by increased levels of C-reactive protein reflect the severity of acute pancreatitis. PMID- 1907252 TI - Human platelet/erythroleukemia cell prostaglandin G/H synthase: cDNA cloning, expression, and gene chromosomal assignment. AB - Platelets metabolize arachidonic acid to thromboxane A2, a potent platelet aggregator and vasoconstrictor compound. The first step of this transformation is catalyzed by prostaglandin (PG) G/H synthase, a target site for nonsteroidal antiinflammatory drugs. We have isolated the cDNA for both human platelet and human erythroleukemia cell PGG/H synthase using the polymerase chain reaction and conventional screening procedures. The cDNA encoding the full-length protein was expressed in COS-M6 cells. Microsomal fractions from transfected cells produced prostaglandin endoperoxide-derived products which were inhibited by indomethacin and aspirin. Mutagenesis of the serine residue at position 529, the putative aspirin acetylation site, to an asparagine reduced cyclooxygenase activity to barely detectable levels, an effect observed previously with the expressed sheep vesicular gland enzyme. Platelet-derived growth factor and phorbol ester differentially regulated the expression of PGG/H synthase mRNA levels in the megakaryocytic/platelet-like HEL cell line. The PGG/H synthase gene was assigned to chromosome 9 by analysis of a human--hamster somatic hybrid DNA panel. The availability of platelet PGG/H synthase cDNA should enhance our understanding of the important structure/function domains of this protein and its gene regulation. PMID- 1907255 TI - Role of parenteral nutrition in Crohn's colitis. PMID- 1907254 TI - Estimation of risk of transmission of non-A, non-B hepatitis by needlestick injury. PMID- 1907256 TI - Liver macrophage-mediated cytotoxicity toward mastocytoma cells involves phagocytosis of tumor targets. AB - Macrophage-mediated cytotoxicity toward tumor cells usually involves extracellular lysis of the targets. In this study, we report that liver macrophages from rats treated with lipopolysaccharide (5 mg/kg, intravenous) also kill certain tumor cell targets by phagocytosis. Liver macrophages were coincubated with P815 mouse mastocytoma cells for 24 to 72 hr at an effector/target ratio of 10:1. Macrophage phagocytosis was characterized by flow cytometry and by light and electron microscopy. For flow-cytometric studies, P815 cells were prelabeled with the fluorescent dye 1,1'-dioctadecyl-3,3,3',3' tetramethyl-indocarbocyanine perchlorate. We found that coincubation of macrophages with labeled targets resulted in a time-dependent increase in macrophage-associated fluorescence, reaching a maximum at 72 hr. This correlated with light-microscopic observations of increased numbers of tumor cells in the macrophages and enhanced macrophage surface area and density. Electron microscopic studies revealed that the initial event in the phagocytic process involved the capture of P815 cells by the pseudopodia of the macrophages. Target cells were then surrounded by lamellipodia, internalized in phagosomes and destroyed. These data, together with previous studies, provide evidence for multiple mechanisms of cytotoxicity mediated by activated liver macrophages. PMID- 1907257 TI - Inhibition of DNA repair and the enhancement of cytotoxicity of alkylating agents. AB - DNA damage was evaluated by flow cytometric (FCM) analysis of cells treated with L-phenylalanine mustard (L-PAM) and stained with anti-DNA monoclonal antibody (MAb) F7-26. DNA damage was rapidly repaired, as indicated by the loss of DNA immunoreactivity after removal of L-PAM. Two types of drug combinations were found to inhibit DNA repair. Combinations containing inhibitors of DNA polymerase (ara-C, aphidicolin) or these inhibitors and hydroxyurea inhibited DNA repair in A2780/PAM and A549 cells. The inhibition of DNA repair by combinations of DNA damaging agents thioTEPA or cisplatin and DNA polymerase inhibitors is a novel observation based on the specificity of DNA damage assay with MAb F7-26. Combinations containing thioTEPA or cisplatin inhibited DNA repair in A549 but not in A2780/PAM cells. Drug combinations which inhibited DNA repair also significantly enhanced cell killing by L-PAM. Cell survival in cultures treated with L-PAM and efficient inhibitors was 2 to 3 orders of magnitude lower than was expected for additive survival. ThioTEPA and cisplatin play a dual role in combination chemotherapy by inducing DNA damage and inhibiting repair of DNA damage. FCM analysis of DNA repair may be a useful component of drug evaluation and could be applied to determine cell-type specific sensitivity to inhibitors of DNA repair. PMID- 1907258 TI - Effect of physical exercise on in vitro production of interleukin 1, interleukin 6, tumour necrosis factor-alpha, interleukin 2 and interferon-gamma. AB - The present study was designed to examine the effect of physical exercise on production of interleukin-1 (IL-1), interleukin-6 (IL-6), tumour necrosis factor alpha (TNF-alpha), interleukin-2 (IL-2) and interferon-gamma (IFN-gamma). Ten young, healthy volunteers underwent 60-min bicycle exercise at 75% of maximal oxygen uptake (VO2max). Blood samples were collected before and during the last minutes of exercise, as well as 2 h and 24 h later. Blood mononuclear cells (BMNC) were stimulated in vitro with either bacterial lipopolysaccharide or phytohaemagglutinin, and the supernatants were tested for the above-mentioned cytokines using bioassays as well as ELISA techniques. The production of IL-6 increased significantly 2 h after exercise, furthermore the production of IL-1 alpha and IL-1 beta was enhanced, although only borderline significant. TNF alpha, IL-2 and IFN-gamma did not fluctuate in relation to exercise. The increased amounts of IL-1 and IL-6 in the supernatants generated from a fixed number of BMNC are most likely explained by the increased percentage and absolute number of blood monocytes 2 h after exercise. IL-2 and IFN-gamma are mainly produced by CD4+ and CD16+ cells. During exercise the CD4+ subset decreases, while the CD16+ subset increases. The finding of unchanged production of IL-2 and IFN-gamma was therefore expected. PMID- 1907259 TI - Manganese dipyridoxyl diphosphate. Effect of dose, time, and pulse sequence on hepatic enhancement in rats. AB - We used an animal model to investigate the hepatic enhancement characteristics of manganese dipyridoxyl diphosphate (MnDPDP) related to time, dose, and pulse sequence. The contrast doses selected were in the human tolerance range. Using an SE 300/15 pulse sequence, maximum mean hepatic enhancement of 45% (8 mumols/kg) and 58% (12 mumols/kg) over baseline was seen during a plateau maintained between 5 and 50 minutes postinjection in the 8 mumols/kg group, and between 10 and 90 minutes in the 12 mumols/kg group. This plateau was followed by a very gradual decline in hepatic enhancement. Using either 4 or 8 mumols/kg, there was a significant increase in postcontrast hepatic intensity on all relatively T1 weighted pulse sequences (spin echo [SE] 300/15, inversion recovery [IR] 1400/20/400, gradient echo [GE] 47/13/80 degrees, and GE 60/20/30 degrees) except GE 47/13/80 degrees at 4 mumols/kg. At 8 mumols/kg there was superior enhancement, with IR 1400/20/400 and SE 300/15, but at 4 mumols/kg there was no consistently superior sequence. None of the relatively T2-weighted pulse sequences (SE 2000/50, SE 2000/100, or GE 100/30/20 degrees) demonstrated a significant change in hepatic intensity using either dose of contrast. The data suggest that the best combination of dose, pulse sequence, and time for hepatic imaging with MnDPDP is 8 mumols/kg using heavily T1-weighted sequences 5 to 60 minutes following contrast administration. PMID- 1907260 TI - Gelman Sciences Safe protective mouthpieces. PMID- 1907261 TI - Forma Scientific CO2 incubators. PMID- 1907262 TI - Cloning and DNA sequence of amiC, a new gene regulating expression of the Pseudomonas aeruginosa aliphatic amidase, and purification of the amiC product. AB - Using in vitro-constructed deletions and subcloned DNA fragments, we have identified a new gene, amiC, which regulates expression of the inducible Pseudomonas aeruginosa aliphatic amidase activity. The DNA sequence of the gene has been determined, and an open reading frame encoding a polypeptide of 385 amino acids (molecular mass, 42,834 Da) has been identified. A search of sequence libraries has failed to find homologies with other published sequences. The amiC translation termination codon (A)TGA overlaps the initiation codon for the downstream amiR transcription antitermination factor gene, implying that the amiCR operon is coordinately regulated. Disruption of the amiC open reading frame by insertion and deletion leads to constitutive amidase synthesis, suggesting that AmiC is a negative regulator. This is confirmed by the finding that a broad host-range expression vector carrying amiC (pSW41) represses amidase expression in a series of previously characterized P. aeruginosa amidase-constitutive mutants. The AmiC polypeptide has been purified from PAC452(pSW41), and N terminal amino acid sequencing has confirmed the gene identification. PMID- 1907263 TI - In situ studies on incorporation of nucleic acid precursors into Chlamydia trachomatis DNA. AB - Chlamydiae are obligate intracellular bacteria that are dependent on eukaryotic host cells for ribonucleoside triphosphates. The purpose of the present study was to determine whether Chlamydia trachomatis obtains deoxyribonucleotides from the host cell. The study was aided by the finding that host and parasite DNA synthesis activity could be distinguished by their differing sensitivities to aphidicolin and norfloxacin. Results from isotope incorporation experiments indicated that any nucleobase or ribonucleoside that could serve as a precursor for host DNA synthesis could also be utilized by C. trachomatis for DNA replication. C. trachomatis utilized only those precursors which the host cell converted to the nucleotide level. Pyrimidine deoxyribonucleotides were efficient precursors for host DNA synthesis; however, they were not used by C. trachomatis. On the other hand, purine deoxyribonucleosides are rapidly catabolized by host cells, it is necessary to regulate their metabolism to determine whether they serve as direct precursors for C. trachomatis DNA synthesis. This was partially achieved by using a hypoxanthine-guanine phosphoribosyltransferase-negative cell line and using deoxycoformycin and 8-aminoguanosine as inhibitors of (deoxy)adenosine deaminase and purine nucleoside phosphorylase, respectively. The results indicated that purine deoxyribonucleosides are efficiently utilized for host cell DNA synthesis even if degradation pathways are inhibited and salvage to ribonucleotides is minimized. In sharp contrast, the purine deoxyribonucleosides were utilized by C. trachomatis as precursors for DNA synthesis only when host catabolic pathways and salvage reactions were intact. High-pressure liquid chromatographic analysis of nucleotide pools extracted from host cells pulsed with radiolabeled precursors suggests that infected cells transport and phosphorylate all deoxynucleosides as effectively as mock-infected control cultures. In aggregate, these results show that chlamydiae do not take up deoxyribonucleotides from the host cells. PMID- 1907264 TI - Engineering a Bacillus subtilis expression-secretion system with a strain deficient in six extracellular proteases. AB - We describe the development of an expression-secretion system in Bacillus subtilis to improve the quality and quantity of the secreted foreign proteins. This system consists of a strain (WB600) deficient in six extracellular proteases and a set of sacB-based expression vectors. With the inactivation of all six chromosomal genes encoding neutral protease A, subtilisin, extracellular protease, metalloprotease, bacillopeptidase F, and neutral protease B, WB600 showed only 0.32% of the wild-type extracellular protease activity. No residual protease activity could be detected when WB600 was cultured in the presence of 2 mM phenylmethylsulfonyl fluoride. By using TEM beta-lactamase as a model, we showed that WB600 can significantly improve the stability of the secreted enzyme. To further increase the production level we constructed an expression cassette carrying sacY, a sacB-specific regulatory gene. This gene was placed under the control of a strong, constitutively expressed promoter, P43. With this cassette in the expression vector, an 18-fold enhancement in beta-lactamase production was observed. An artificial operon, P43-sacY-degQ, was also constructed. However, only a partial additive enhancement effect (24-fold enhancement) was observed. Although degQ can stimulate the production of beta-lactamase in the system, its ability to increase the residual extracellular protease activity from WB600 limits its application. The use of the P43-sacY cassette and WB600 would be a better combination for producing intact foreign proteins in high yield. PMID- 1907265 TI - Cofactor requirements of BamHI mutant endonuclease E77K and its suppressor mutants. AB - A mutant BamHI endonuclease, E77K, belongs to a class of catalytic mutants that bind DNA efficiently but cleave DNA at a rate more than 10(3)-fold lower than that of the wild-type enzyme (S. Y. Xu and I. Schildkraut, J. Biol. Chem. 266:4425-4429, 1991). The preferred cofactor for the wild-type BamHI is Mg2+. BamHI is 10-fold less active with Mn2+ as the cofactor. In contrast, the E77K variant displays an increased activity when Mn2+ is substituted for Mg2+ in the reaction buffer. Mutations that partially suppress the E77K mutation were isolated by using an Escherichia coli indicator strain containing the dinD::lacZ fusion. These pseudorevertant endonucleases induce E. coli SOS response (as evidenced by blue colony formation) and thus presumably nick or cleave chromosomal DNA in vivo. Consistent with the in vivo result, the pseudorevertant endonucleases in the crude cell extract display site-specific partial DNA cleavage activity. DNA sequencing revealed two unique suppressing mutations that were located within two amino acid residues of the original mutation. Both pseudorevertant proteins were purified and shown to increase specific activity at least 50-fold. Like the wild-type enzyme, both pseudorevertant endonucleases prefer Mg2+ as the cofactor. Thus, the second-site mutation not only restores partial cleavage activity but also suppresses the metal preference as well. These results suggest that the Glu-77 residue may play a role in metal ion binding or in enzyme activation (allosteric transition) following sequence-specific recognition. PMID- 1907266 TI - AlgR, a response regulator controlling mucoidy in Pseudomonas aeruginosa, binds to the FUS sites of the algD promoter located unusually far upstream from the mRNA start site. AB - Strong transcriptional activation of algD, a key event in the overproduction of alginate and establishment of mucoidy in Pseudomonas aeruginosa, depends on the functional algR gene. The predicted gene product of algR shows homologies to response regulators from bacterial signal transduction systems. The algR gene was overexpressed in Escherichia coli, its product (AlgR) was purified by utilizing its apparent affinity for heparin, and its sequence was verified by partial amino acid sequence analysis. AlgR was found to interact directly with the algD promoter. Deletion mapping analysis, in conjunction with mobility shift DNA binding assays, indicated the presence of three regions within the algD promoter capable of specifically binding AlgR. A relatively weak interaction was observed with the algD promoter fragment containing the region immediately upstream of the algD mRNA start site (-144 to +11). However, when fragments spanning regions located very far upstream from the algD mRNA initiation site (-533 and -332) were used, strong specific binding was observed. These regions were separated by a DNA segment not binding AlgR and spanning positions -332 to -144. DNase I footprinting analysis further established the presence of discrete AlgR binding sites overlapping with FUS, the far-upstream sites required for full induction of algD transcription and its environmental modulation. There were two distinct binding sites: RB1, spanning nucleotides -479 to -457, and RB2, spanning nucleotides -400 to -380. Both of these sequences shared a highly conserved core region, ACCGTTCGTC. These results established a direct interaction of AlgR with the algD promoter and revealed an arrangement of binding sites highly unusual for response regulators of the AlgR type. PMID- 1907268 TI - Cysteine, even in low concentrations, induces transient amino acid starvation in Escherichia coli. AB - Cysteine, in concentrations down to 0.04 micrograms/ml, induces transient amino acid starvation in Escherichia coli growing in minimal medium. The duration depends on the concentration and is 5 min at 2 micrograms of cysteine per ml. At low cysteine concentrations, threonine and isoleucine almost completely abolish the starvation. PMID- 1907269 TI - Chemical modification of an ecotropic murine leukemia virus results in redirection of its target cell specificity. AB - An ecotropic virus was chemically modified in order to determine whether its target cell specificity could be altered. We hypothesized that chemical coupling of galactose residues to a virus might permit specific infection of hepatocytes mediated by asialoglycoprotein receptors unique to these cells. To test this hypothesis, we took advantage of the fact that: 1) artificial asialoglycoproteins can be created by chemical coupling of lactose to proteins; and 2) viruses that are ecotropic have a narrow species specificity. An ecotropic, rodent-specific, replication-defective murine leukemia virus containing the gene for beta galactosidase was chemically modified with lactose to contain 5.9 mumol of lactose per mg of viral RNA. Modified and unmodified viruses were incubated for 5 days with HepG2, a human hepatoma line that possesses asialoglycoprotein receptors, and SK Hep1, a human cell line that does not. As expected from the ecotropism, unmodified virus did not produce beta-galactosidase activity in either cell type. Modified virus did not produce beta-galactosidase activity in SK Hep1 cells. However, modified virus did produce beta-galactosidase activity, 71.2 units/mg of cell protein, in the human receptor (+) HepG2 cells. Interestingly, modification of the virus also resulted in decreased enzyme activity in previously susceptible host rodent cells. Competition with modified virus by an excess of an asialoglycoprotein completely prevented development of enzymatic activity in HepG2 cells. Histochemical treatment of cells with 5-bromo 4-chloro-3-indoyl beta-D-galactoside to detect in situ beta-galactosidase activity demonstrated that only HepG2 cells treated with modified virus were positive and that 36% of these cells were stained after 5 days. These data indicate that chemical modification of a virus can result in a redirection of the infectivity of the virus toward hepatocyte-derived cells mediated by the presence of asialoglycoprotein receptors. PMID- 1907267 TI - rbcR [correction of rcbR], a gene coding for a member of the LysR family of transcriptional regulators, is located upstream of the expressed set of ribulose 1,5-bisphosphate carboxylase/oxygenase genes in the photosynthetic bacterium Chromatium vinosum. AB - An open reading frame, rbcR, was identified 226 bp upstream of rbcAB, i.e., the ribulose 1,5-bisphosphate carboxylase genes expressed in the phototrophic purple bacterium Chromatium vinosum. Several features reveal that rbcR encodes a member of the LysR family of transcriptional regulators, in which an anomalous content of lysine and arginine residues (Lys/Arg anomaly) was found. The expression of rbcR in Escherichia coli as a protein fused to the N-terminal region of beta galactosidase led to reduced expression of rbcAB. Thus, rbcR is likely to encode a trans-acting transcriptional regulator of rbcAB expression in C. vinosum. PMID- 1907270 TI - Unique characteristics of superoxide dismutase of a strictly anaerobic archaebacterium Methanobacterium thermoautotrophicum. AB - The superoxide dismutase (SOD) gene of Methanobacterium thermoautotrophicum (Takao, M., Oikawa, A., and Yasui, A. (1990) Arch. Biochem. Biophys. 283, 210 216), a strictly anaerobic archaebacterium, was expressed in Escherichia coli. The gene product accounted for more than 30% of the host's soluble protein. The purified protein was an active iron-containing tetrameric SOD with specific activity similar to known manganese-containing SODs (MnSODs) of aerobic archaebacteria. Although M. thermoautotrophicum SOD is an iron-containing SOD (FeSOD), it resembles MnSODs in amino acid sequence as judged by criteria distinguishing FeSODs from MnSODs. Moreover, M. thermoautotrophicum SOD is resistant to azide and hydrogen peroxide as MnSODs are, suggesting that its evolution is distinct from known eubacterial FeSODs. PMID- 1907271 TI - GTPase-deficient G alpha i2 oncogene gip2 inhibits adenylylcyclase and attenuates receptor-stimulated phospholipase A2 activity. AB - The GTPase activity of a G protein alpha subunit functions as a timer to control the lifetime of the activated conformation of the protein. Expression of the GTPase-deficient Gi2 alpha subunit oncogene, gip2 (alpha i2Q205L), in Chinese hamster ovary cells inhibited the stimulation of adenylylcyclase and altered the calcium regulation of the Gi2-phospholipase A2 (PLA2) effector complex. The phenotypic consequence of the activated alpha i2 mutant on hormonal stimulation of PLA2 varied depending on the cytoplasmic calcium transient elicited by different Gi2-linked receptors. The stimulation of PLA2 by thrombin, which mobilized calcium only from internal stores, was markedly attenuated in gip2 expressing cells. In contrast, the attenuation of the PLA2 response to ATP, a purinergic agonist which mobilizes calcium from both extracellular space and internal stores, was significantly less than that observed for thrombin. Ionomycin, a calcium ionophore, stimulated PLA2 activity in clones which expressed gip2 to a level similar to that observed in wild-type Chinese hamster ovary cells. Thus, the dominant GTPase-deficient gip2 polypeptide will constitutively inhibit adenylylcyclase but differentially modulate enzymes regulated by calcium and coupled to Gi2. PMID- 1907272 TI - A highly conserved sequence of the Arg-Gly-Asp-binding domain of the integrin beta 3 subunit is sensitive to stimulation. AB - The Arg-Gly-Asp (RGD)-binding domain of GPIIb-IIIa has been localized in a fragment of the GPIIIa subunit that includes the sequence between amino acids 109 and 171. To examine, in a platelet membrane environment, the activated versus nonactivated status of this domain, we have produced a monoclonal antibody against a synthetic peptide (residues 109-128) located within the RGD-binding region on GPIIIa. This kappa-IgM, named AC7, was specific for GPIIIa peptide 109 128 and interacted only with activated platelets. Fibrinogen, RGDF peptide, and the fibrinogen phi chain decapeptide LGGAKQAGDV inhibited the binding of AC7 to ADP-stimulated platelets. AC7 IgM and "small fragments" inhibited fibrinogen binding and platelet aggregation in a dose-dependent fashion. Induction of AC7 binding by D33C, a monoclonal antibody recognizing the GPIIb 426-437 sequence and stimulating fibrinogen binding, indicated that the GPIIb 426-437 and the GPIIIa 109-128 sequences were both involved in a stimulation-dependent conformational modification of the receptor. AC7 was able to recognize beta subunits other than GPIIIa on leucocyte surfaces but only after cell fixation with glutaraldehyde. The results are consistent with the implication of the RGD-binding domain in receptor ligand interaction on the platelet surface and its conformational modification and exposure upon receptor induction. PMID- 1907273 TI - The novel tungsten-iron-sulfur protein of the hyperthermophilic archaebacterium, Pyrococcus furiosus, is an aldehyde ferredoxin oxidoreductase. Evidence for its participation in a unique glycolytic pathway. AB - The anaerobic archaebacterium, Pyrococcus furiosus, grows optimally at 100 degrees C by a fermentative-type metabolism in which H2, CO2, and organic acids are end products. The growth of this organism is stimulated by tungsten, and, from it, a novel, red-colored, tungsten-iron-sulfur protein, abbreviated RTP, has been purified (Mukund, S., and Adams, M. W. W. (1990) J. Biol. Chem. 265, 11508 11516). RTP (Mr approximately 85,000) contained approximately 1W, 7Fe, and 5 acid labile sulfide atoms/molecule and exhibited unique EPR properties. The physiological function of the protein, however, was unknown. We show here that RTP is an inactive form of an aldehyde ferredoxin oxidoreductase (AOR). The active enzyme was obtained by rapid purification under anaerobic conditions using buffers containing dithiothreitol and glycerol. AOR catalyzed the oxidation of a range of aliphatic aldehydes with an optimum temperature for activity above 90 degrees C, but it did not oxidize glucose or glyceraldehyde 3-phosphate, nor reduce NAD(P), and its activity was independent of CoA. The active (AOR) and inactive (RTP) forms of the enzyme were indistinguishable in their contents of metals and acid-labile sulfide and in their EPR properties. The latter are though to originate from two nonidentical and spin-coupled iron-sulfur clusters, whereas the tungsten in this enzyme, which was not detectable by EPR, appears to be present as a novel pterin cofactor. Inhibition and activation studies indicated that AOR contains a catalytically essential W-SH group that is not present in RTP, the inactive form. AOR is a new type of aldehyde-oxidizing enzyme and is the first aldehyde oxidoreductase to be purified from an archaebacterium or a nonactogenic anaerobic bacterium. Its physiological role in P. furiosus is proposed as the oxidation of glyceraldehyde to glycerate in a unique, partially nonphosphorylated, glycolytic pathway that generates acetyl-CoA from glucose without the participation of nicotinamide nucleotides. PMID- 1907274 TI - Unique glycosylation of three keratan sulfate proteoglycan isoforms. AB - Recent work demonstrates isoforms of bovine corneal keratan sulfate proteoglycan containing structurally unique core proteins of 25 and 37 kDa (Funderburgh, J., and Conrad, G. (1990) J. Biol. Chem. 265, 8297-8303). In the current study, two forms (37A and 37B) of the 37-kDa protein were separated by ion-exchange chromatography after removal of keratan sulfate with endo-beta-galactosidase. Keratan sulfate linkage sites in core proteins were labeled with UDP [3H]galactose using galactosyltransferase. Labeled proteins were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and analyzed by tryptic digestion and reversed-phase chromatography. The 37A protein has three keratan sulfate-linkage sites, and the 37B and 25-kDa proteins each contain one linkage site. Reversed-phase tryptic maps of the three proteins differed in total peptide profile and in glycosylated peptides labeled with periodate-[3H]-NaBH4. Tryptic mapping of the two 37-kDa isoforms after deglycosylation showed differences in total tryptic peptides, in peptides labeled with [14C]iodoacetic acid, and in peptides recognized by antibodies to a mixture of the 37-kDa cores. Antibody to a synthetic peptide with N-terminal sequence obtained from mixed 37-kDa cores reacted exclusively with the 37B isoform. These results show that bovine corneal keratan sulfate proteoglycan has three different core proteins each with distinct glycosylation and unique primary structure. PMID- 1907275 TI - Subhemolytic doses of Escherichia coli hemolysin evoke large quantities of lipoxygenase products in human neutrophils. AB - Polymorphonuclear leukocytes (PMN) have been identified as preferred target cells for Escherichia coli hemolysin in human blood (Bhakdi, S., Greulich, S., Muhly, M., Eberspacher, B., Becker, H., Thiele, A., and Hugo, F. (1989) J. Exp. Med. 169, 737-754). Leukotriene and 5-hydroxyeicosatetraenoic acid generation was investigated in human PMN challenged with E. coli hemolysin in the absence or presence of free arachidonic acid or eicosapentaenoic acid (EPA). In the absence of exogenous free fatty acids, E. coli hemolysin (0.01-10 hemolytic units/ml) induced moderate generation of leukotriene B4 (LTB4) and its omega-oxidation products. The presence of free arachidonic acid (10 microM) during E. coli hemolysin (0.1 hemolytic unit/ml) challenge evoked the generation of large quantities of these products (greater than 100 pmol/1.5 x 10(7) PMN). In parallel, large amounts of 5-hydroxyeicosatetraenoic acid and nonenzymatic LTA4 hydrolysis products appeared. Product release peaked or plateaued 5-10 min after E. coli hemolysin challenge. The presence of exogenous EPA upon E. coli hemolysin challenge resulted in the exclusive generation of LTB5 and metabolites, LTA5 decay products and 5-hydroxyeicosapentaenoic acid. Dose and time dependences corresponded to those with arachidonic acid provision, and the total of EPA derived products surpassed that of arachidonic acid metabolites in corresponding experiments approximately 2-fold. Increasing the time between free fatty acid provision and E. coli hemolysin challenge resulted in a rapid decline in the generation of arachidonic acid or EPA metabolites. Thus, subhemolytic doses of E. coli hemolysin evoke marked PMN eicosanoid generation that is dependent on exogenous free fatty acid supply, with total amounts approximating those found in calcium ionophore-stimulated neutrophils. PMID- 1907276 TI - Expression, assembly, and processing of an active plant ferredoxin-NADP+ oxidoreductase and its precursor protein in Escherichia coli. AB - The flavoprotein ferredoxin-NADP+ reductase (FNR) catalyzes the final step of the photosynthetic electron transport chain, i.e. the reduction of NADP+ by ferredoxin. A cloned FNR cDNA from a pea library (Newman, B., and Gray, J. (1988) Plant Mol. Biol. 10, 511-520) was used to construct plasmids which express the apoenzyme in Escherichia coli. Two recombinant vectors were prepared, one containing the sequence corresponding to the mature enzyme and another including, in addition, the sequence of the transit peptide that directs FNR to the chloroplast. These proteins were expressed as fusion products to the NH2-terminal portion of beta-galactosidase. In both cases, a 35-kDa immunoreactive polypeptide was the major product, suggesting that the proteins were processed in vivo. NH2 terminal sequence determination of the purified recombinant proteins indicate cleavage at positions -1/-2 with respect to the normal processing site in chloroplasts. The processed enzymes showed enzymatic activities and spectral properties that were similar or identical to those of native plant FNR. When a La protease-deficient E. coli strain was used as a host, the expressed FNR precursor was found to be poorly processed, associated to bacterial pellets, and showed no detectable FNR activity. The overall results indicate that acquisition of the native enzyme conformation and assembly of the prosthetic group takes place in the bacterial host, generating an enzyme that is, as far as studied, indistinguishable from plant FNR. PMID- 1907277 TI - Role of threonine 190 in modulating the catalytic function of malate dehydrogenase from a thermophile Thermus flavus. AB - Random mutagenesis of malate dehydrogenase from a thermophilic bacterium, Thermus flavus AT-62, had revealed that a Thr190----Ile replacement near the essential catalytic residue His187 caused marked modulation of the catalytic properties. For further exploration of a role of the residue at this position, this residue was substituted with each of the other amino acids by site-directed mutagenesis. Most of the mutations except for substitution with Ser caused increases in Km for oxaloacetate and increases Ki for oxaloacetate of 2-110 times. Substitution with His or Pro was characterized by the complete loss of substrate inhibition, along with a marked increase in Km for oxaloacetate. Kinetic analyses of the native and altered malate dehydrogenases at various pHs revealed that both Km and Ki for oxaloacetate decreased proportionally to the decrease in pH from 8.40 to 5.75, whereas kcat was nearly constant within the pH range. Apparent shifts of the optimum pH values toward acidity observed with most of the altered malate dehydrogenases were attributed to the increase in Ki, which facilitated the release from the substrate inhibition at a lower pH. Replacement of Thr310, a possible counterpart with which Thr190 forms a hydrogen bond, by Ile caused changes in the catalytic properties similar to those of the Thr190-substituted enzymes. These results suggest that not only the loss of the hydrogen bond between Thr190 and Thr310 but also properties of the residues introduced at position 190 cause modulation of the catalytic properties, probably through dislocation of the loop structure that contains the catalytic residue His187. PMID- 1907278 TI - Catalytic triad residue mutation (Asp156----Gly) causing familial lipoprotein lipase deficiency. Co-inheritance with a nonsense mutation (Ser447----Ter) in a Turkish family. AB - We studied the molecular basis of familial Type I hyperlipoproteinemia in two brothers of Turkish descent who had normal plasma apolipoprotein C-II levels and undetectable plasma post-heparin lipoprotein lipase (LPL) activity. We cloned the cDNAs of LPL mRNA from adipose tissue biopsies obtained from these individuals by the polymerase chain reaction and directional cloning into M13 vectors. Direct sequencing of pools of greater than 2000 cDNA clones indicates that their LPL mRNA contains two mutations: a missense mutation changing codon 156 from GAU to GGU predicting an Asp156----Gly substitution and a nonsense mutation changing the codon for Ser447 from UCA to UGA, a stop codon, predicting a truncated LPL protein that contains 446 instead of 448 amino acid residues. Both patients were homozygous for both mutations. Analysis of genomic DNAs of the patients and their family members by the polymerase chain reaction, restriction enzyme digestion (the GAT----GGT mutation abolishes a TaqI restriction site), and allele-specific oligonucleotide hybridization confirms that the patients were homozygous for these mutations at the chromosomal level, and the clinically unaffected parents and sibling were true obligate heterozygotes for both mutations. In order to examine the functional significance of the mutations in this family, we expressed wild type and mutant LPLs in vitro using a eukaryotic expression vector. Five types of LPL proteins were produced in COS cells by transient transfection: (i) wild type LPL, (ii) Asp156----Gly mutant, (iii) Ser447----Ter mutant, (iv) Gly448 ---Ter mutant, and (v) Asp156----Gly/Ser447----Ter double mutant. Both LPL immunoreactive mass and enzyme activity were determined in the culture media and intracellularly. Immunoreactive LPLs were produced in all cases. The mutant LPLs, Asp156----Gly and Asp156----Gly/Ser447----Ter, were devoid of enzyme activity, indicating that the Asp156----Gly mutation is the underlying defect for the LPL deficiency in the two patients. The two mutant LPLs missing a single residue (Gly448) or a dipeptide (Ser447-Gly448) from its carboxyl terminus had normal enzyme activity. Thus, despite its conservation among all mammalian LPLs examined to date, the carboxyl terminus of LPL is not essential for enzyme activity. We further screened 224 unrelated normal Caucasians for the Ser447----Ter mutation and found 36 individuals who were heterozygous and one individual who was homozygous for this mutation, indicating that it is a sequence polymorphism of no functional significance. Human LPL shows high homology to hepatic triglyceride lipase and pancreatic lipase.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1907279 TI - Actin, troponin C, Alzheimer amyloid precursor protein and pro-interleukin 1 beta as substrates of the protease from human immunodeficiency virus. AB - We show here for the first time that actin, troponin C, Alzheimer amyloid precursor protein (AAP), and pro-interleukin 1 beta (pro-IL-1 beta), are substrates of the protease encoded by the human immunodeficiency virus (HIV) type 1. As has been seen in other non-viral protein substrates of the HIV protease, the presence of Glu residues in the P2' position appears to play an important role in substrate recognition. Three of the four bonds cleaved in actin, two of the three in troponin C, and all of the bonds hydrolyzed in AAP and pro-IL-1 beta have a P2' Glu residue. In fact, Glu residues are accommodated in all positions from P4 to P4' surrounding the scissile bond in substrates of the HIV proteases, and as many as 4 adjacent Glu residues were seen in one of the bonds cleaved in AAP. This study of non-viral protein substrates has also revealed unexpected amino acids such as Gly, Arg, and Glu in the scissile bond itself rather than the more conventional hydrophobic amino acids. The HIV-2 protease hydrolyzed actin in a manner similar to that of the HIV-1 enzyme, but its cleavage of troponin C was distinct in that it split a bond adjacent to a triplet of Glu residues in P2, P3, and P4 that was refractory to the HIV-1 enzyme. Documentation of cleavage sites in the several important cellular proteins noted above has extended our understanding of the features in a substrate that are recognized by these multi sub-site proteases of retroviral maturation. Moreover, the present work adds to an accumulating body of evidence which demonstrates that these enzymes can damage crucial structural and regulatory cellular proteins if ever their activity is expressed outside the viral particle itself. PMID- 1907280 TI - Single chain urokinase. Augmentation of enzymatic activity upon binding to monocytes. AB - Cellular migration typically requires cell surface-associated urokinase-type plasminogen activator (u-PA) and plasminogen, both of which are present as proenzymes. Because each active enzyme can activate the other zymogen, the mechanism by which the initial proteolytic event of this two-zymogen system occurs is unclear. A mutant of single chain u-PA that could not be cleaved to the more active two-chain u-PA was used to demonstrate that (i) u-PA in its single chain form exhibits a reactive active site serine, (ii) the enzymatic activity of this molecule is augmented 100-fold upon binding to the u-PA receptor on monocytes as compared with the enzymatic activity of the same number of molecules in the fluid phase, and (iii) the molecule thus bound and active remains in the single-chain form. This is likely an important mechanism for the initiation and control of cell surface-associated fibrinolysis. PMID- 1907281 TI - Nucleotide sequence, transcriptional analysis, and expression of genes encoded within the form I CO2 fixation operon of Rhodobacter sphaeroides. AB - In Rhodobacter sphaeroides, many of the structural genes encoding enzymes of the Calvin cycle are duplicated and grouped within two separate clusters. In this study, the nucleotide sequence of a 5627-base pair region of DNA that contains the form I Calvin cycle gene cluster has been determined. The five open reading frames are arranged in the order, fbpA prkA cfxA rbcL rbcS and are tightly linked and oriented in the same direction. The results of insertional mutagenesis studies suggest the genes are organized within an operon. Consistent with this proposal, the cfxA gene has been tentatively identified as a gene encoding the Calvin cycle enzyme, aldolase. Measurement of the activities of various Calvin cycle enzymes in the insertion mutants showed that inactivation of genes within one CO2 fixation cluster affected expression of genes within the second cluster, revealing a complex regulatory network. PMID- 1907282 TI - Human lysosomal protective protein has cathepsin A-like activity distinct from its protective function. AB - The protective protein was first discovered because of its deficiency in the metabolic storage disorder galactosialidosis. It associates with lysosomal beta galactosidase and neuraminidase, toward which it exerts a protective function necessary for their stability and activity. Human and mouse protective proteins are homologous to yeast and plant serine carboxypeptidases. Here, we provide evidence that this protein has enzymatic activity similar to that of lysosomal cathepsin A: 1) overexpression of human and mouse protective proteins in COS-1 cells induces a 3-4-fold increase of cathepsin A-like activity; 2) this activity is reduced to approximately 1% in three galactosialidosis patients with different clinical phenotypes; 3) monospecific antibodies raised against human protective protein precipitate virtually all cathepsin A-like activity in normal human fibroblast extracts. Mutagenesis of the serine and histidine active site residues abolishes the enzymatic activity of the respective mutant protective proteins. These mutants, however, behave as the wild-type protein with regard to intracellular routing, processing, and secretion. In contrast, modification of the very conserved Cys60 residue interferes with the correct folding of the precursor polypeptide and, hence, its intracellular transport and processing. The secreted active site mutant precursors, endocytosed by galactosialidosis fibroblasts, restore beta-galactosidase and neuraminidase activities as effectively as wild-type protective protein. These findings indicate that the catalytic activity and protective function of the protective protein are distinct. PMID- 1907283 TI - Isolation and characterization of developmentally regulated chondroitin sulfate and chondroitin/keratan sulfate proteoglycans of brain identified with monoclonal antibodies. AB - A panel of monoclonal antibodies prepared to the chondroitin sulfate proteoglycans of rat brain was used for their immunocytochemical localization and isolation of individual proteoglycan species by immunoaffinity chromatography. One of these proteoglycans (designated 1D1) consists of a major component with an average molecular size of 300 kDa in 7-day brain, containing a 245-kDa core glycoprotein and an average of three 22-kDa chondroitin sulfate chains. A 1D1 proteoglycan of approximately 180 kDa with a 150-kDa core glycoprotein is also present at 7 days, and by 2-3 weeks postnatal this becomes the major species, containing a single 32-kDa chondroitin 4-sulfate chain. The concentration of 1D1 decreases during development, from 20% of the total chondroitin sulfate proteoglycan protein (0.1 mg/g brain) at 7 days postnatal to 6% in adult brain. A 45-kDa protein which is recognized by the 8A4 monoclonal antibody to rat chondrosarcoma link protein copurifies with the 1D1 proteoglycan, which aggregates to a significant extent with hyaluronic acid. A chondroitin/keratan sulfate proteoglycan (designated 3H1) with a size of approximately 500 kDa was isolated from rat brain using monoclonal antibodies to the keratan sulfate chains. The core glycoprotein obtained after treatment of the 3H1 proteoglycan with chondroitinase ABC and endo-beta-galactosidase decreases in size from approximately 360 kDa at 7 days to approximately 280 kDa in adult brain. In 7-day brain, the proteoglycan contains three to five 25-kDa chondroitin 4-sulfate chains and three to six 8.4-kDa keratan sulfate chains, whereas the adult brain proteoglycan contains two to four chondroitin 4-sulfate chains and eight to nine keratan sulfate chains, with an average size of 10 kDa. The concentration of 3H1 increases during development from 3% of the total soluble proteoglycan protein at 7 days to 11% in adult brain, and there is a developmental decrease in the branching and/or sulfation of the keratan sulfate chains. A third monoclonal antibody (3F8) was used to isolate a approximately 500-kDa chondroitin sulfate proteoglycan comprising a 400-kDa core glycoprotein and an average of four 28-kDa chondroitin sulfate chains. In the 1D1 and 3F8 proteoglycans of 7-day brain, 20 and 33%, respectively, of the chondroitin sulfate is 6-sulfated, whereas chondroitin 4-sulfate accounts for greater than 96% of the glycosaminoglycan chains in the adult brain proteoglycans.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1907284 TI - Limunectin. A phosphocholine-binding protein from Limulus amebocytes with adhesion-promoting properties. AB - A protein that binds to and precipitates with pneumococcal C-polysaccharide and a phosphocholine (PC) derivative of bovine serum albumin has been affinity purified from Limulus amebocytes. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis reveals that the isolated protein consists of a single polypeptide chain of approximately 50 kDa. It is an intracellular protein localized in the secretory granules of amebocytes according to immunogold staining. Although it shares the PC-binding property with C-reactive protein isolated from Limulus and other animal species, it differs from C-reactive protein in that the latter binds to PC only in the presence of Ca2+, whereas the newly isolated protein binds to PC in a Ca(2+)-independent manner. In this respect, the newly isolated PC-binding protein resembles the antibodies to PC of mouse myelomas. The gene coding for this protein has been isolated. The gene sequence predicts a protein of 54 kDa with an unusual structural feature: it consists almost entirely of 10 contiguous segments, 45 amino acids in length, with extensive homology. Some limited sequence homologies were found between the 54-kDa protein and segments of vitronectin, gelatinase, and collagenase. It binds to bacterial cells, fixed amebocytes, and a number of extracellular matrix molecules. Due to its structural and some functional similarities to other adhesion molecules, the Limulus 54-kDa protein was named "Limunectin." PMID- 1907285 TI - Endocytosis of the ASGP receptor H1 is reduced by mutation of tyrosine-5 but still occurs via coated pits. AB - The clustering of plasma membrane receptors in clathrin-coated pits depends on determinants within their cytoplasmic domains. In several cases, individual tyrosine residues were shown to be necessary for rapid internalization. We have mutated the single tyrosine at position 5 in the cytoplasmic domain of the major subunit H1 of the asialoglycoprotein receptor to alanine. Expressed in fibroblasts cells, the mutant protein was accumulated in the plasma membrane, and its rate of internalization was reduced by a factor of four. The residual rate of endocytosis, however, was still significantly higher than that of resident plasma membrane proteins. Upon acidification of the cytoplasm, which specifically inhibits the formation of clathrin-coated vesicles but not uptake of the fluid phase marker Lucifer yellow, residual endocytosis was blocked. By immunoelectron microscopy mutant H1 could be directly demonstrated in coated pits. The fraction of wild-type and mutant H1 present in coated pits as determined by immunogold localization correlated well with the respective rates of internalization. Thus, mutation of tyrosine-5 only partially inactivates recognition of H1 for incorporation into coated pits. PMID- 1907286 TI - Effects of protein I of Neisseria gonorrhoeae on neutrophil activation: generation of diacylglycerol from phosphatidylcholine via a specific phospholipase C is associated with exocytosis. AB - Upon engagement of chemoattractant receptors, neutrophils generate inositol trisphosphate and diacylglycerol (DG) by means of a phosphatidylinositol-specific phospholipase C (PI-PLC) which is regulated by a GTP-binding protein(s). We have previously reported (Reibman, J., H. M. Korchak, L. B. Vosshall, K. A. Haines, A. M. Rich, and G. Weissmann. 1988. J. Biol. Chem. 263:6322-6328) a biphasic rise in DG after exposure of neutrophils to the chemoattractant FMLP: a rapid (less than or equal to 15 s) phase ("triggering") and a slow (greater than or equal to 30 s) phase ("activation"). These derive from distinct intracellular lipid pools. To study the source of rapid and slow DG, we have used a unique probe, protein I, a porin that is the major outer membrane protein of Neisseria gonorrhoeae. Treatment of neutrophils with protein I inhibits exocytosis and homotypic cell adhesion provoked by FMLP without inhibiting assembly of the NADPH oxidase responsible for O2-. generation. DG turnover in PMN labeled with [3H]arachidonate and [14C]glycerol was profoundly altered by protein I. Whereas the rapid peak of DG was only modestly diminished (FMLP vs. FMLP plus protein I = DG labeled with [3H]arachidonic acid (3H-a.a.-DG): 142 +/- 14% SEM vs. 125 +/- 22%; DG labeled with the glycerol backbone with [14C]glycerol (D-14C-G): 125 +/- 10% SEM vs. 107 +/- 8.5% SEM), the slow rise in both 3H-a.a.-DG and D-14C-G was essentially abolished. Moreover, treatment of neutrophils with 4-4'-diisothiocyanatostilbene 2,2'-disulfonic acid (DIDS), which, like protein I, inhibits exocytosis without affecting O2-. generation also inhibited slow DG. However, protein phosphorylation and dephosphorylation (47phox, 66phox) were unaffected in the absence of slow DG. To determine the source of the slow DG, we have analyzed radiolabeled phospholipid (PL) turnover after FMLP +/- protein I (P.I.). Treatment of PMN with FMLP (0.1 microM) resulted in breakdown of phosphatidylcholine (PC), beginning at 30 s, and reaching a nadir at 60 s (3H-PC = 59 +/- 10.2% SEM of resting, 14C-PC = 57 +/- 6.4%). Protein I (0.25 microM) significantly inhibited PC turnover after FMLP ([3H]PC = 95 +/- 5.6% and [14C]PC = 86 +/- 8.4% of resting at 60 s), but failed to alter the metabolism of 3H- or 14C-phosphatidylinositol after FMLP (91 +/- 19.6 and 88 +/- 16.5% vs. 92 +/- 9.2 and 91 +/- 16% at 60 s).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1907288 TI - Direct evidence for spatial and temporal regulation of transforming growth factor beta 1 expression during cutaneous wound healing. AB - The expression of transforming growth factor (TGF beta 1) protein in human and porcine skin has been analyzed by immunohistochemistry with two polyclonal antibodies (anti-CC and anti-LC) following cutaneous injury. The anti-LC antibody binds intracellular TGF beta 1 constitutively expressed in the nonproliferating, differentiated suprabasal keratinocytes in the epidermis of normal human skin, while the anti-CC antibody does not react with the form of TGF beta 1 present in normal skin as previously shown. TGF beta 1 may play a role in wound healing as suggested by its effect on multiple cell types in vitro and its acceleration of wound repair in animals. We have evaluated the natural expression and localization of TGF beta 1 protein in situ during initiation, progression, and resolution of the wound healing response in two models of cutaneous injury: the human suction blister and the dermatome excision of partial thickness procine skin. Anti-CC reactive TGF beta 1 in the epidermis is rapidly induced within 5 minutes following injury and progresses outward from the site of injury. The induction reflects a structural or conformational change in TGF beta 1 protein and can be blocked by the protease inhibitor leupeptin or by EDTA, suggesting a change in TGF beta 1 activity. One day post-injury anti-CC reactive TGF beta 1 is present in all epidermal keratinocytes adjacent to the wound including the basal cells. This corresponds temporally to the transient block of the basal keratinocyte mitotic burst following epithelial injury. Three to 4 days post injury anti-CC reactive TGF beta 1 is localized around the suprabasal keratinocytes, in blood vessels, and in the papillary dermis in cellular infiltrates. The exclusion of TGF beta 1 from the rapidly proliferating basal cells and its extracellular association with suprabasal keratinocytes may represent physiological compartmentation of TGF beta 1 activity. Anti-CC staining is strong in the leading edge of the migrating epithelial sheet. The constitutive anti-LC reactivity with suprabasal keratinocytes seen in normal epidermis is neither relocalized nor abolished adjacent to the injury, but anti-LC staining is absent in the keratinocytes migrating within the wound. As the wound healing response resolves and the skin returns to normal, anti-CC reactive TGF beta 1 disappears while constitutive anti-LC reactive TGF beta 1 persists. Thus, changes in the structure or conformation of TGF beta 1, its localization, and perhaps its activity vary in a spatial and temporal manner following cutaneous injury and correlate with physiological changes during wound healing. PMID- 1907289 TI - Heavy metals induce expression of the TPA-inducible sequence (TIS) genes. AB - We previously cloned a set of primary response genes, which we call TIS (TPA Inducible Sequence) genes, from a cDNA library prepared from Swiss 3T3 cells treated with tetradecanoyl phorbol acetate (TPA) and cycloheximide. TPA, polypeptide growth factors, and serum induce TIS gene expression in 3T3 cells. We now report that cadmium and zinc elevate mRNA levels for the TIS genes, including TIS28 (c-fos), in Swiss 3T3 cells. The time-course of TIS gene mRNA accumulation after metal exposure is delayed in comparison to the accumulation of TIS gene mRNA after treatment with TPA and growth factors. Cadmium induction of the TIS gene message accumulation is blocked by actinomycin D. Moreover, cadmium treatment does not significantly stabilize TIS gene messages. TIS gene induction by metal is a primary response; TIS8, which encodes a zinc-finger transcription factor, and TIS28 (c-fos) can be induced in the presence of cadmium and cycloheximide, an inhibitor of protein synthesis. Down-regulation of protein kinase C does not attenuate TIS gene induction by heavy metals. PMID- 1907287 TI - Disruption of the actin cytoskeleton after microinjection of proteolytic fragments of alpha-actinin. AB - Alpha-actinin can be proteolytically cleaved into major fragments of 27 and 53 kD using the enzyme thermolysin. The 27-kD fragment contains an actin-binding site and we have recently shown that the 53-kD fragment binds to the cytoplasmic domain of beta 1 integrin in vitro (Otey, C. A., F. M. Pavalko, and K. Burridge. 1990. J. Cell Biol. 111:721-729). We have explored the behavior of the isolated 27- and 53-kD fragments of alpha-actinin after their microinjection into living cells. Consistent with its containing a binding site for actin, the 27-kD fragment was detected along stress fibers within 10-20 min after injection into rat embryo fibroblasts (REF-52). The 53-kD fragment of alpha-actinin, however, concentrated in focal adhesions of REF-52 cells 10-20 min after injection. The association of this fragment with focal adhesions in vivo is consistent with its interaction in vitro with the cytoplasmic domain of the beta 1 subunit of integrin, which was also localized at these sites. When cells were injected with greater than 5 microM final concentration of either alpha-actinin fragment and cultured for 30-60 min, most stress fibers were disassembled. At this time, however, many of the focal adhesions, particularly those around the cell periphery, remained after most stress fibers had gone. By 2 h after injection only a few small focal adhesions persisted, yet the cells remained spread. Identical results were obtained with other cell types including primary chick fibroblasts, BSC-1, MDCK, and gerbil fibroma cells. Stress fibers and focal adhesions reformed if cells were allowed to recover for 18 h after injection. These data suggest that introduction of the monomeric 27-kD fragment of alpha actinin into cells may disrupt the actin cytoskeleton by interfering with the function of endogenous, intact alpha-actinin molecules along stress fibers. The 53-kD fragment may interfere with endogenous alpha-actinin function at focal adhesions or by displacing some other component that binds to the rod domain of alpha-actinin and that is needed to maintain stress fiber organization. PMID- 1907290 TI - Responses of growth cones to changes in osmolality of the surrounding medium. AB - The possible involvement of osmotically generated hydrostatic pressure in driving actin-rich extensions of the cell surface was examined using cultures of chick neurons. Estimation of the excess internal osmotic pressure of chick neural tissue by vapor pressure deficit osmometry, and of the excess internal hydrostatic pressure in cultured chick neurons using a calibrated pressure pipette, gave upper limits of 10 mosM and 0.1 atmosphere (1 atmosphere = 101325 Pa), respectively. Increases in the osmolality of the medium surrounding cultured neurons by addition of sucrose, mannitol or polyethylene glycol by amounts that should eliminate any internal pressure not only failed to arrest the growth of filopodia but caused them to increase in length up to twofold in 3-5 min. Lamellipodia remained unchanged following hyperosmotic shifts of 20 mosM, but higher levels caused a small decrease in area. Reduction of osmolality by the addition of water to the culture fluid down to 50% of its normal value failed to show any detectable change in either filopodial length or lamellipodia area. These observations argue against an osmotic mechanism for growth cone extension and show that the growth of filopodia, in particular, is unlikely to be driven by osmotically generated hydrostatic pressure. In contrast to the short-term effects on growth cone morphology, the slower elongation of the neuritic cylinder showed a consistent osmotic response. Growth rates were reduced following addition of osmolytes and increased in rate (as much as sixfold) following addition of water to the culture medium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1907291 TI - Determination of glibenclamide and its two major metabolites in human serum and urine by column liquid chromatography. AB - A simple reversed-phase liquid chromatographic method for the measurement of low concentrations of glibenclamide (glyburide) and its two major metabolites, 4 trans- and 3-cis-hydroxyglibenclamide, in human serum and urine has been developed. The compounds were extracted with n-hexane-dichloromethane (1:1). The UV detection wavelength was 203 nm. The minimum detectable serum level of glibenclamide was 1 ng ml (2 nM), and the relative standard deviation was 8.9% (n = 9). When maximum sensitivity was desired the metabolites were chromatographed separately. Metabolites in urine were measured by the same method after five-fold sample dilution. The utility of the method was tested on a healthy volunteer who ingested 3.5 mg of glibenclamide. The parent drug was present in the serum for at least 18 h, and the metabolites in the urine for at least 24 h. PMID- 1907292 TI - Determination of melatonin and monoamines in rat pineal using reversed-phase ion interaction chromatography with fluorescence detection. AB - A method is reported for the ion-interaction, reversed-phase separation of 24 compounds (chiefly monoamines) arising from the metabolism of tyrosine and tryptophan. These compounds were separated as two groups. The first group comprised 3,4-dihydroxyphenylethylene glycol, tyrosine, 3-methoxy-4-hydroxyphenyl glycol, 5-hydroxytryptophan, norepinephrine, 3,4-dihydroxyphenylacetic acid, epinephrine, 5-hydroxyindole-3-acetic acid, homovanillic acid, 5 hydroxytryptophol, dopamine, tryptophan. N-acetylserotonin, N-acetyltryptophan, 5 methoxytryptophan and serotonin. The mobile phase consisted of a 6.8:93.2 (v/v) mixture of acetonitrile and an aqueous solution containing 0.16 M ammonium phosphate, 0.06 M citric acid, 0.15 mM disodium EDTA, 10 mM dibutylamine and 6 mM sodium 1-octanesulphonate at pH 4.50. The second group of compounds comprised 6 hydroxymelatonin, 5-methoxyindole-3-acetic acid, indole-3-acetic acid, 5 methoxytryptamine, tryptamine, 5-methoxytryptophol, melatonin and tryptophol. The mobile phase consisted of a 16:84 (v/v) mixture of acetonitrile and an aqueous solution containing 0.05 M ammonium phosphate, 0.05 M citric acid, 0.15 mM disodium EDTA, 25 mM dibutylamine and 5 mM sodium 1-octanesulphonate at pH 5.30. Detection was by fluorescence measurement (lambda ex = 280 nm, lambda em = 340 nm). The proposed method exhibited linear calibration over the biochemically significant concentration range, with detection limits in the 10-200 pg range. Excellent precision for peak areas and retention times was observed, even over a period of 24 h. The applicability of amperometric detection (at 0.72V) is also demonstrated. The method is applied to the determination of monoamines in individual rat pineals. Low nanogram levels of tyrosine, norepinephrine, 5 hydroxyindole-3-acetic acid, tryptophan, serotonin and 6-hydroxymelatonin, and picogram levels of 5-hydroxytryptophan, 5-hydroxytryptophol, 5-methoxyindole-3 acetic acid, indole 3-acetic acid, 5-methoxytryptophol and melatonin were indicated in most of the samples. PMID- 1907293 TI - Statewide collaborative planning: benefits and challenges. AB - This article shares some of the past and present collaborative experiences of Kentucky providers in statewide planning for nursing continuing education (CE). Some of the ingredients for successful statewide planning, as well as the barriers, will be discussed. PMID- 1907294 TI - Benefits and costs of continuing nursing education: an analytical survey. AB - Federal and statutory requirements demand and professional associations, health care agencies, and individual nurses expect benefits from nurses' participation in continuing nursing education (CNE). These benefits include: competence; improved quality of care; personal benefits, such as self-satisfaction; and social benefits, such as shorter hospital stays for patients. However, it is not clear from the literature whether CNE provides what is expected. Also, the costs of CNE are not clear. In this research, 244 registered nurses rated the benefits and identified the costs of CNE via a mailed survey. Personal benefits, accruing to the individual nurse, were rated highest and economic benefits were rated lowest. All cost data were positively skewed (many low costs). Opportunity cost (time lost from work) was higher than either direct (tuition) or indirect (travel, books/supplies, child care, and meals) cost. Employers were found to pay more of the cost of CNE than the individual nurse. No significant relationships were identified between the costs and the benefits of CNE. PMID- 1907295 TI - A tiger by the tail: tackling barriers to differentiated practice. AB - Nurses in South Dakota are moving forward with new models for nursing practice. Consensus-building efforts led to the development of a conference focused on differentiated nursing practice. The Nominal Group Process was an effective tool for the identification of strategies to implement new models of nursing practice. The concept of differentiated practice has significant implications for continuing nursing educators as they work with existing nurses to create a new pattern for nursing. PMID- 1907296 TI - Distance education: joining forces to meet the challenge. AB - This paper describes a unique initiative between Manitoba Health and Brandon University to meet the current challenge of distance education for community health nurses employed by Manitoba Health. In November 1988, a strategy paper was approved, allowing Manitoba Health to contract with Brandon University to facilitate access to university courses. Incentives to encourage Manitoba Health employees to take advantage of these courses included reimbursement for work time and travel and hotel costs to attend associated laboratory sessions provided at off-campus sites (distance education). These incentives provided employees with evidence of tangible support for continuing education. This pioneering venture between two complex organizations demonstrated commitment to further education as well as the ability to initiate a collaborative enterprise. PMID- 1907297 TI - Self-instructional posters: one way to save time and money. AB - Getting staff to continuing education programs can be difficult due to time, staffing, and cost restraints. A self-instructional module combined with a teaching poster format has had a favorable response from participants. This format has the capability of reaching a higher number of participants and is both time- and cost-effective. PMID- 1907298 TI - The ethical dilemma. AB - Nursing leaders need to respect the professional contributions of other nurse colleagues. Therefore, it is very important that a presenter deliver only material for which he or she has the rights. To preserve good relationships between the two teachers, the first teacher needs to respect the colleague's material, while also clarifying his or her rights to teach the material. PMID- 1907299 TI - Incorporating the affective component into an AIDS workshop. AB - Caring for persons infected with the human immunodeficiency virus (HIV) and with acquired immunodeficiency syndrome (AIDS) will be a growing challenge for nurses in the years to come. It the nursing profession is to meet this challenge, continuing education will be essential. This article presents an approach to using a range of community and academic resources in the provision of continuing education. The 1-day program described includes updated information on HIV etiopathogenesis, clinical spectrum, epidemiology, transmission, prevention, and research, and gives participants an opportunity to explore their feelings and attitudes toward providing care for persons with HIV. PMID- 1907300 TI - Inhibition of Clostridium tyrobutyricum by bacteriocin-like substances produced by lactic acid bacteria. AB - Lactic acid bacteria were selected for their inhibitory activity against Clostridium tyrobutyricum under conditions that eliminate the effects of lactic acid and hydrogen peroxide. Four strains were isolated belonging to the species Lactococcus lactis ssp. lactis. The sensitivity of the inhibitory substances to pronase and trypsine indicates that they are proteins or peptides different from nisin. Their resistance to phospholipase D indicates that they are also different from lactostrepcin. The inhibitory substances are produced during the exponential phase of growth. Their activity is bactericidal and directed toward some strains of Clostridium tyrobutyricum, Lactobacillus helveticus, and Streptococcus thermophilus, but strains used as dairy starters, Lactobacillus lactis, Streptococcus thermophilus, and Propionibacterium shermanii, are not all affected by the inhibition. PMID- 1907301 TI - Injury and death of frozen Listeria monocytogenes as affected by glycerol and milk components. AB - A cell suspension of Listeria monocytogenes strain Scott A in phosphate buffer solution alone or with added glycerol, milk fat, lactose, or casein was frozen and stored at -18 degrees C. At suitable intervals, samples of cell suspensions were thawed at 35 degrees C and plated on suitable media to distinguish between surviving injured and noninjured cells of L. monocytogenes. Glycerol (2 or 4%) protected L. monocytogenes from death and injury during frozen storage for up to 6 mo; however, when 2% glycerol was present, 30 min of frozen storage had to elapse after completion of freezing before protection against death was evident. During short-term (2 wk or less) frozen storage, lactose, milk fat, and casein, each at 2%, provided better protection to L. monocytogenes than did 2% glycerol. During long-term frozen storage, milk components, each at 2%, protected L. monocytogenes against death and injury, but less than that provided by glycerol. Protection by lactose and milk fat against death during frozen storage was observed during 4 wk and against injury during 5 mo and 4 wk of frozen storage, respectively. Protection by casein against death and injury occurred during frozen storage for up to 6 mo. Salts that simulate milk ultrafiltrate provided almost no protection to L. monocytogenes during freezing and frozen storage. Increasing the concentration of milk fat from 2 to 4% resulted in almost no change in death of L. monocytogenes, but in a decrease in injury only during the first 24 h of frozen storage.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1907302 TI - Strains and suspending menstrua as factors affecting death and injury of Listeria monocytogenes during freezing and frozen storage. AB - Cell suspensions of Listeria monocytogenes strains V7, California, and Ohio in phosphate buffer solution, tryptose broth, or milk were frozen and stored at -18 degrees C. At appropriate intervals during storage, a sample was thawed at 35 degrees C and surface-plated on suitable media to allow colony formation by noninjured or noninjured plus injured cells. Degrees of death and injury were calculated from the data. Cells of L. monocytogenes were more resistant to death and injury when they were suspended in milk or tryptose broth rather than phosphate buffer solution. There was a significant (two-way ANOVA) difference in resistance to death and injury during frozen storage among strains of L. monocytogenes suspended in tryptose broth. The difference was nonsignificant when the cells were suspended in phosphate buffer solution or milk. Listeria monocytogenes strain Ohio was more resistant to death and injury during frozen storage when cells were suspended in tryptose broth rather than milk. The opposite was true for strains V7 and California. Death and injury of L. monocytogenes strains V7, California, and Ohio suspended in phosphate buffer solution were 98.7, 97.9, and 91.2% and 77.5, 51.6, and 70.2%, respectively, after 4 wk of frozen storage. The values were 67.3, 91.6, and 42.3% and 44.4, 65.6, and 32.6%, respectively, when cells were suspended in tryptose broth, and they were 37.8, 40, and 60.7% and 10.8, 66.8, and 46%, respectively, when cells were suspended in milk. PMID- 1907303 TI - Antigenic homology among gram-negative organisms isolated from cattle with clinical mastitis. AB - This study examined the degree of serologic homology among mastitis pathogens. Antibodies were raised against the Rc mutant, Escherichia coli O111:B4 (strain J5) and affinity purified against lipopolysaccharide derived from the Ra mutant, Salmonella typhimurium TV119. These antibodies reacted with a battery of unrelated Gram-negative bacteria in whole cell ELISA. Bacteria with strong cross reactions included a heterologous, smooth E. coli, Salmonella dublin, S. typhimurium, Salmonella newport, and Pseudomonas aeruginosa. Recognition of Klebsiella pneumoniae and Bordetella bronchisepticum was observed, but reactions were weaker than with the other isolates. The reduced recognition of these isolates probably reflects a masking effect of the bacterial capsule and variations in lipopolysaccharide structure. The polyclonal antibody did not recognize a Gram-positive isolate, Staphylococcus aureus. These immunoglobulins were then tested using whole cell ELISA against a panel of bacteria recovered from the mammary glands of cattle with clinical mastitis. Marked reactivity was noted against a variety of Gram-negative pathogens. Gram-positive isolates had lower recognition by Gram-negative core antigen specific immunoglobulin. The results suggest immunization with rough mutant bacteria may have broad application in the prevention of coliform mastitis. PMID- 1907305 TI - Nonrandom use of J alpha gene segments. Influence of V alpha and J alpha gene location. AB - TCR genes (alpha, beta, gamma, and delta) undergo rearrangement during development in the thymus. The repertoire of alpha beta and gamma delta cells is shaped first by genetic processes that control rearrangement and expression and then by intercellular processes that "select" cells expressing only particular receptors. In this report, alpha chain transcripts from different stages of ontogeny were examined to determine the influence of V and J gene location on the thymic repertoire. J alpha gene segments were not used equally by V alpha genes. The frequency of J alpha use, and thus the alpha chain repertoire, was influenced by at least three factors: the location of the V gene, the location of the J gene, and the age of the animal. V genes that are proximal to the J alpha region preferentially use the most 5' J alpha gene segments. In contrast, a V alpha gene that is distal to the J alpha region was rarely joined to these same 5' J alpha gene segments in thymocytes from adult animals. We suggest that the data are most easily explained by the frequent occurrence of secondary rearrangements in which a V alpha J alpha rearranged gene would be replaced by the joining of a flanking V alpha gene to a flanking J alpha gene segment. Finally, the evidence suggests that there may be differences in the extent of secondary rearrangements between fetal and adult animals. PMID- 1907304 TI - Autoantibody-encoding kappa L chain genes frequently rearranged in lambda L chain expressing chronic lymphocytic leukemia. AB - Patients with kappa L chain expressing chronic lymphocytic leukemia (CLL) frequently have leukemia cells reactive with a murine mAb, designated 17.109. Raised against a monoclonal IgM rheumatoid factor autoantibody, this mAb recognizes a major kappa-L chain-associated cross reactive Id, designated 17.109 CRI. Molecular studies reveal that the 17.109-CRI in CLL is a serologic marker for expression of a conserved kappa L chain V region gene (V Kappa gene) of the V Kappa 3 subgroup, designated Humkv325. We isolated an upstream gene fragment of Humkv325 to examine for Ig gene rearrangements of this and other closely related V Kappa 3 genes by Southern analyses. Consistent with Humkv325 encoding the 17.109-CRI, we find that the genomic DNA from all 17.109-reactive leukemia cell populations have gene rearrangements that are detected using this probe. In addition, we observe V Kappa 3 gene rearrangements frequently in the genomic DNA of lambda L chain-expressing leukemia cells. Of the genomic DNA from 33 lambda-L chain-expressing CLL samples, 8 (24%) had additional nongerm-line bands detected with the Humkv325 probe. Consistent with these bands representing Ig gene rearrangements, the additional band in each but one sample also hybridized with probes specific for the J Kappa region and/or the kappa-deleting element. Using the polymerase chain reaction (PCR), we examined the genomic DNA from all lambda L chain-expressing CLL for V Kappa 3 gene rearrangements to J Kappa and/or Kde. PCR on each DNA sample with V Kappa 3 gene rearrangements detected by Southern analysis generated gene fragments that hybridized specifically with oligonucleotides corresponding to framework or CDR of the Humkv325 gene. Nucleic acid sequence analyses of representative samples confirmed that these DNA contained abortive Humkv325 gene rearrangements. PCR for rearranged V Kappa 3 genes in the DNA of other lambda-L chain-expressing CLL either did not generate any PCR product or produced fragments that failed to hybridize with all Humkv325 oligonucleotide probes. Nucleic acid sequence analyses of the latter demonstrated that these represent abortive V Kappa gene rearrangements involving another conserved V Kappa 3 gene, designated Vg. These studies indicate that Humkv325 and Vg frequently may undergo Ig gene rearrangement independent of their expression. As such, the frequent use of Humkv325 in CLL may be secondary, in part, to an enhanced propensity of this V Kappa 3 gene to undergo genetic rearrangement during B cell ontogeny. PMID- 1907306 TI - Restricted T cell expression of IL-2/IFN-gamma mRNA in human inflammatory disease. AB - It has been difficult to demonstrate functionally distinct T cell populations in humans on the basis of cytokine secretion. As previous investigators have examined the T cell cytokine profile from immunized animals, we examined whether Th1 or Th2 type T cells could be identified in the peripheral blood or cerebrospinal fluid (CSF) immune compartments from subjects with or without inflammatory diseases. Using limiting dilution analysis and growth with PHA and IL-2/IL-4, we directly cloned a total of 177 T cells from the peripheral blood and CSF of seven subjects, four with inflammatory disease and three control subjects, and examined the cytokine message profile after stimulation with ionomycin and PMA. We found that most clones from both the peripheral blood and CSF express IL-1, IL-2, IL-4, IFN-gamma, or TNF-alpha cytokine mRNA after activation with ionomycin and PMA. All T cell clones tested produced TNF-alpha mRNA, and all but 14 produced IFN-gamma mRNA. As reported previously, Th0 cells, which produced IFN-gamma, IL-2, IL-4, and IL-5 mRNA, were found in most subjects. In striking contrast, Th1 cells, which expressed IL-2 and IFN-gamma but not IL-4 or IL-5 mRNA, were present in both peripheral blood and CSF of subjects with inflammatory disease but not found in peripheral blood or CSF of subjects without systemic inflammation. Th2 cells, expressing IL-4 and IL-5 but not IFN-gamma or IL-2 mRNA, were not found in any subject. These data present the first evidence for Th1 T cell clones in humans that may be associated with systemic inflammation. PMID- 1907307 TI - Reversal of defective IL-6 production in lipopolysaccharide-tolerant mice by phorbol myristate acetate. AB - The development of LPS tolerance has been suggested to be mediated by an inhibition of cytokine synthesis. Here we have studied serum IL-6 and TNF levels in mice after LPS administration. Repeated administration of LPS (35 micrograms daily for 4 days) to mice induced a refractoriness (tolerance) to subsequent administrations of LPS in terms of induction of circulating IL-6 and TNF. To investigate the mechanism by which LPS down-regulates its own induction of cytokine synthesis and the relationship between IL-6 and TNF production, we attempted to revert the inhibition of IL-6 and TNF production using agents like PMA or IFN-gamma, previously reported to activate macrophage production of cytokines. Pretreatment with PMA (4 micrograms, 10 min before LPS) partially restored IL-6 production in LPS-tolerant mice given 2 micrograms LPS. On the other hand, PMA did not restore TNF induction in LPS-tolerant mice, even when administered with high doses of LPS (up to 200 micrograms). A similar reversal of LPS resistance to IL-6, but not TNF, induction by PMA was observed in genetically LPS-resistant C3H/HeJ mice. IFN-gamma also restored, although to a lesser extent than PMA, IL-6 production. However, unlike PMA, IFN-gamma could also partially restore TNF production in LPS-tolerant mice, although only when LPS was administered at high doses. By contrast with PMA, IFN-gamma was clearly more active in restoring TNF synthesis than that of IL-6. Similar results were obtained in genetically LPS-unresponsive C3H/HeJ mice. These data suggest that different mechanisms are implicated in the inhibition of IL-6 and TNF synthesis in LPS-tolerant mice and that part of this inhibition can be overcome by PMA or IFN-gamma. PMID- 1907309 TI - Activation by bacterial lipopolysaccharide causes changes in the cytosolic free calcium concentration in single peritoneal macrophages. AB - Variations in the cytosolic free Ca2+ concentration [( Ca2+]i) upon LPS exposure were studied in single rat peritoneal macrophages loaded with fura-2 under carefully controlled conditions. Of a total of 60 cells examined, 47% responded to LPS (1 microgram/ml) with an increase in [Ca2+]i. Macrophages were heterogeneous with regard to the LPS response, with individual cells exhibiting single rapid and transient increases in [Ca2+]i, multiple transients, or slower and more sustained variations. In 62% of the responding cells, a second exposure to LPS elicited a [Ca2+]i rise, although usually to a slightly lower peak value. Thus, rapid desensitization to LPS does not occur in the majority of these macrophages. EGTA did not abolish the response of those cells that exhibited a single rapid transient in [Ca2+]i, indicating that the source of the initial [Ca2+]i rise was the intracellular stores. There was no obvious correlation between the type of response to LPS and the initial morphologic features (rounded vs polarized) of the cells. Our present work shows unequivocally that LPS induces increases in macrophage [Ca2+]i and, thereby, lends substantial support to the hypothesis that [Ca2+]i is a second messenger in LPS-mediated activation of the macrophage. PMID- 1907308 TI - Amino acid sequence of the FV region of a human monoclonal IgM (NOV) with specificity for the capsular polysaccharide of the group B meningococcus and of Escherichia coli K1, which cross-reacts with polynucleotides and with denatured DNA. AB - The complete amino acid sequences of the VH and VL regions of a biologically significant Ig, IgMNOV, were determined. IgMNOV is reactive with the capsular polysaccharide of the group B meningococcus and of Escherichia coli K1. As reported earlier, it cross-reacts completely with polynucleotides poly(A) and poly(I) and to a lesser extent with denatured DNA and protects newborn rats against infection with E. coli K1, and is equal in potency to the standard horse anti-group B meningococcal serum. The reduced and alkylated chains were sequenced directly, identifying the L chain as lambda-subgroup II and the mu-H chain as subgroup III. The complete sequence of the VL region was determined by sequencing peptides generated by cleavage with Staphylococcus aureus protease, chymotrypsin, and trypsin. The H chain was cleaved with cyanogen bromide followed by enzymatic cleavages to obtain a large part of the VH region sequence. The structure was completed by sequencing tryptic peptides of the Fab fragment and by mass spectrometric analysis. PMID- 1907310 TI - In vivo molecular analysis of lymphokines involved in the murine immune response during Schistosoma mansoni infection. I. IL-4 mRNA, not IL-2 mRNA, is abundant in the granulomatous livers, mesenteric lymph nodes, and spleens of infected mice. AB - Using Northern Blot analysis, the endogenous levels of IL-4 and IL-2 mRNA in the spleens, mesenteric lymph nodes, and granulomatous livers of male CBA/J mice in the acute phase of infection with Schistosoma mansoni have been quantified. High levels of IL-4 mRNA were detected in all three tissues from infected mice, whereas none was detected in tissues from normal, uninfected, age-matched mice. Isolation of the granulomas from the livers of infected mice and subsequent extraction of total RNA from these lesions resulted in a 70-fold enrichment of IL 4 message compared with the whole, unseparated granulomatous liver tissue. Hence, the predominant source of the IL-4 mRNA detected in livers from infected mice appears to be the schistosome egg-induced granulomas within these livers. In contrast, IL-2 mRNA was never detected in any of these tissues from either infected or normal mice. Control experiments were performed that ruled out the possibility that this inability to detect IL-2 mRNA was due to a difference in the efficacy of the IL-4 and IL-2 probes or due to a selective lability of IL-2 message. These data imply that IL-4-producing, Th2 lymphocytes are active in and possibly integral to the granulomatous, delayed-type hypersensitivity response characteristic of this infection, and directly challenges the current hypothesis that delayed-type hypersensitivity responses are exclusively mediated by Th1 lymphocytes. PMID- 1907311 TI - High energy radiation: high tech warfare against cancer. PMID- 1907312 TI - Brain microvessel 12-hydroxyeicosatetraenoic acid is the (S) enantiomer and is lipoxygenase derived. AB - 12-Hydroxyeicosatetraenoic acid (12-HETE) production from arachidonic acid by cerebral microvessels isolated from perfused adult murine brain was reduced by the lipoxygenase inhibitors baicalein, esculetin, gossypol, nordihydroguaiaretic acid, and quercetin. Except for quercetin and gossypol, the IC50 did not exceed 10 microM. Each inhibitor, except baicalein, also decreased microvessel prostaglandin production when present in concentrations above their IC50 value for 12-HETE. In contrast, inhibitors of the cytochrome P450 monooxygenase system, clotrimazole, metyrapone, and proadifen (SKF-525A), had little effect on microvessel 12-HETE production. Chiral phase HPLC analysis revealed that only the (S) enantiomer of 12-HETE was formed. The major microvessel metabolite of eicosapentaenoic acid co-eluted with 12-hydroxyeicosapentaenoic acid (12-HEPE) on reverse-phase HPLC and the (S) enantiomer of 12-HEPE on chiral phase HPLC. Furthermore, like 12-HETE, 12-HEPE production was blocked by lipoxygenase inhibitors. These studies demonstrate that brain microvessels produce only the (S) enantiomeric 12-hydroxy derivatives of both arachidonic acid and eicosapentaenoic acid by the action of a lipoxygenase that can be selectively inhibited by baicalein. Since arachidonic acid and eicosapentaenoic acid are available to cerebral blood vessels in certain pathological settings, these 12 hydroxy acid lipoxygenase products may mediate some of the cerebrovascular dysfunction that occurs following stroke, brain trauma, or seizures. PMID- 1907313 TI - Dietary (n-3) fatty acids alter fatty acid composition and prostaglandin synthesis in rat testis. AB - The objective of this study was to determine the efficacy of linolenic acid [18:3(n-3)], compared with the long-chain (n-3) fatty acids in fish oil, in suppressing arachidonic acid [20:4(n-6)] metabolism in rat testis. Six groups of rats were fed three levels of 18:3(n-3) or fish oil, and the fatty acid composition of testis parenchyma lipids and prostaglandin (PG) I2 synthesis by tunica were determined after 12 wk. Levels of docosapentaenoic acid [22:5(n-6)], the major 22-carbon fatty acid in rat testis lipids, were significantly depressed compared with the control by both linolenic acid and fish oil; however, testis weights were not affected significantly. Arachidonic acid levels also were depressed significantly in testis lipids by dietary (n-3) fatty acids, but the decreases were not as pronounced as those observed in other tissues. The synthesis of PGI2 was significantly reduced compared with the control by (n-3) fatty acid feeding, but there were no differences among the experimental groups. Both 18:3(n-3) and the longer-chain (n-3) fatty acids from fish oil reduce levels of 20:4(n-6) and 22:5(n-6) in testis lipids and the capacity of the tunica to synthesize PGI2, but these fatty acids seem to cause no defect in testicular development as indicated by weight. PMID- 1907314 TI - Protein quality and quantity influence free amino acid levels in the brain and serum of rats during lactation. AB - Diets containing 11 or 21% protein supplied by wheat, wheat + lysine + threonine or casein + methionine were fed to pregnant rats from conception until d 4 or 8 of lactation. Dams then were decapitated, serum was collected and brains and left inguinal-abdominal mammary glands were quickly excised and weighed. Serum and brains were frozen in liquid nitrogen and stored at -70 degrees C. Free amino acids in either serum or brain were not significantly different on d 8 as compared with d 4 of lactation. Increasing dietary protein quality or quantity increased concentrations of most essential amino acids in serum and brain. Changes in the concentrations of nonessential amino acids in serum or brain associated with increases in protein quality or quantity were variable. For all 16 amino acids measured, brain free amino acids were highly correlated with serum levels. In this experiment, pup growth varied from 0.3 g/d for the offspring of dams fed 11% wheat to 1.4 g/d for the offspring of dams fed 21% wheat + lysine + threonine. Concentrations of lysine and threonine in the brain were more than twice as high under the latter as compared with the former condition, but differences in all other amino acids among the dietary groups were small, ranging from -20% for glycine to +21% for leucine and isoleucine. PMID- 1907315 TI - Magnesium deficiency affects plasma lipoprotein composition in rats. AB - Weanling rats were pair-fed for 8 d with control and Mg-deficient diets containing 960 and 30 mg of Mg/kg, respectively. The marked reduction in plasma Mg levels indicated that the rats fed the Mg-deficient diet were indeed deficient. In the Mg-deficient rats the percent composition of triglycerides in VLDL, LDL and HDL was elevated and that of protein was reduced. Although the proportion of cholesterol was reduced in LDL and HDL, that of phospholipid was decreased only in HDL. Magnesium deficiency induced a decrease in the percent composition of apolipoprotein (apo) E and a relative increase in the apo C for VLDL. In HDL from Mg-deficient rats, the proportion of apo AI was higher than normal, apo AIV was lower than normal and apo E was virtually absent. The percent composition of oleic and linoleic acids was increased but that of stearic and arachidonic acids was depressed in both VLDL and HDL derived from Mg-deficient rats compared with pair-fed controls. Whether these alterations in lipoprotein profile contribute to hyperlipoproteinemia or are the results of the metabolic changes that produce hyperlipoproteinemia remain to be determined. PMID- 1907316 TI - Threonine concentration in the prepyriform cortex has separate effects on dietary selection and intake of a threonine-imbalanced diet by rats. AB - Dietary selection and intake of a threonine-imbalanced diet were evaluated after increasing the concentration of the dietary limiting amino acid in the prepyriform cortex. Selection against the threonine-imbalanced diet in favor of a protein-free diet was reversed when 2 or 4 nmol threonine was injected bilaterally into the prepyriform cortex. However, intake of the threonine imbalanced diet was significantly increased only after injection of 2 nmol threonine. The reduced intake of the threonine-imbalanced diet, compared to the basal diet, after injection of 4 nmol threonine was not the result of an excess in the concentration of amino acid (or nitrogen) injected into the PPC because intake of the threonine-basal diet was not reduced when 4 nmol threonine was administered. Intake of the threonine-imbalanced diet was also increased after injection of 2 nmol threonine plus 2 nmol isoleucine but not after injections of 2 nmol isoleucine. The changes in food intake when an imbalanced diet is fed appear to be the result of at least two separable responses: recognition of a diet as having an amino acid imbalance, as indicated by dietary choice, and reduction in food intake. The results of this study indicate that changing the concentration of the dietary limiting amino acid in the prepyriform cortex influenced dietary selection and food intake separately. PMID- 1907317 TI - Comparison of acellular and whole-cell pertussis-component diphtheria-tetanus pertussis vaccines in infants. The APDT Vaccine Study Group. AB - In a multicenter, double-blind, randomized, longitudinal study, 252 children received licensed Lederle diphtheria-tetanus toxoids and pertussis vaccine adsorbed (DTP) at 2, 4, and 6 months of age, and 245 children received a DTP vaccine with the Lederle/Takeda acellular pertussis component (APDT) at the same ages. Both groups of children received APDT vaccine at 18 months of age. After each of the first three immunizations, APDT vaccine recipients had fewer local and systemic reactions than did DTP vaccinees. Reactions after the 18-month APDT vaccination were minimal in severity regardless of the vaccine previously received. Antibody responses to lymphocytosis-promoting factor and agglutinogens were more pronounced in DTP recipients; however, APDT recipients had a better serologic response to filamentous hemagglutinin, and responses to the 69K protein were equivalent. This APDT vaccine produces fewer reactions than the standard whole-cell DTP vaccine. The protective significance of the serologic responses to the APDT vaccine is unknown, but the greater response to filamentous hemagglutinin and equivalent response to the 69K protein compared with those to DTP vaccine seem promising. PMID- 1907318 TI - Early bacteriologic, immunologic, and clinical courses of young infants with cystic fibrosis identified by neonatal screening. AB - To understand better the events associated with the initiation of lung disease in young children with cystic fibrosis (CF), we prospectively performed a longitudinal study examining the early bacteriologic, immunologic, and clinical courses of 42 children with CF diagnosed after identification by neonatal screening. Serial evaluations included history and physical examination, chest radiographs, throat cultures for bacteria, and determinations of serum immunoglobulin levels and circulating immune complexes. At a mean follow-up age of 27 months, 19% of the children had serial throat cultures positive for Pseudomonas aeruginosa; the first positive culture was found at a mean age of 21 months. In three infants the initial P. aeruginosa isolates were mucoid. As determined by typing with a DNA probe, serial P. aeruginosa isolates from each patient were identical over time but were genetically distinct from isolates recovered from other patients. Of 11 infants with P. aeruginosa, nine (82%) had previous isolates of Staphylococcus aureus or Haemophilus influenzae; all had received prior antibiotic therapy. In comparison with other infants with CF, children with P. aeruginosa grown on serial throat cultures more frequently had daily cough (p less than 0.01), lower chest radiograph scores (p less than 0.05), and elevated levels of circulating immune complexes (p less than 0.01). None of the study infants had persistent hypogammaglobulinemia or hypergammaglobulinemia. We conclude that (1) S. aureus and H. influenzae remain the isolates most frequently recovered from infants with CF; (2) initial recovery of P. aeruginosa by throat culture is often preceded by the onset of chronic respiratory signs; (3) elevations of circulating immune complexes can occur early, often after the initial recovery of P. aeruginosa; and (4) early P. aeruginosa isolates are genetically distinct, demonstrating the lack of cross-colonization in this newborn population. PMID- 1907319 TI - Deficient human immunodeficiency virus type 1-specific cytotoxic T cell responses in vertically infected children. AB - Cytotoxic T lymphocyte (CTL) responses to human immunodeficiency virus type 1 (HIV-1) gag proteins were studied prospectively in 17 children (12 infected) born of mothers with HIV-1 seropositivity and in five pediatric patients with hemophilia infected by transfusion of HIV-1-contaminated factor VIII concentrate. B lymphoblastoid cells infected with vaccinia virus vectors expressing HIV-1 gag gene products were combined with autologous peripheral blood mononuclear cells to detect circulating CTLs. Effector cells were defined by monoclonal antibody mediated, complement-dependent cytolysis. Circulating HIV-1 gag-specific cytotoxic responses were detectable in 4 of 5 HIV-1-infected pediatric hemophilic patients, and were similar in magnitude to those previously described in adults. In contrast, circulating HIV-1 gag-specific cytolysis was detectible in only 3 of 12 vertically infected children. Depletion data revealed that the majority of detectible gag-specific cytolysis was CD8 T cell-mediated. No apparent relationships between CD4 T cell counts, CD8 T cells counts, or serum p24 antigen levels and CTL responses were seen. Deficient CTL development may, in part, explain the more rapid onset of symptomatic disease following vertical HIV infection. PMID- 1907320 TI - Need for the lead mobilization test in children with lead poisoning. AB - We evaluated the recommendation of the Centers for Disease Control, that children with moderate lead poisoning undergo the lead mobilization test (LMT) to determine the need for a full course of chelation treatment. Current criteria for selection for this test include a blood Pb concentration (bPb) between 25 and 55 micrograms/dl and an erythrocyte protoporphyrin level greater than 35 micrograms/dl. To determine whether the eligibility criteria could be refined to a smaller group of patients, we compared bPb determinations obtained on the day of the LMT in 198 children with moderate Pb poisoning to the results of the LMT. We found that children with bPb less than 25 micrograms/dl were unlikely to respond to the test dose of calcium disodium ethylenediamine tetraacetate with a Pb diuresis (24/25 patients had low urinary Pb excretion on the LMT). In contrast, 88% of children with bPb greater than or equal to 40 micrograms/dl were likely to excrete sufficient Pb to indicate the need for a full course of chelation. We conclude that the LMT is indicated for children with bPbs between 25 and 40 micrograms/dl. Children with bPb between 40 and 55 micrograms/dl may receive chelation therapy without having an LMT, if the performance of the LMT is not practical. Patients with levels less than 25 micrograms/dl should be followed clinically and removed from further Pb exposure. PMID- 1907321 TI - Myocardial infarction in a girl with primary antiphospholipid syndrome. PMID- 1907322 TI - Localization of tissue plasminogen activator on experimental microthrombi in rats. Microautoradiographic observations. AB - The localization of tissue plasminogen activator (t-PA) on microthrombi in various organs of disseminated intravascular coagulation rats (DIC rats) was investigated by using microautoradiographic technique. After the injection of [125I]fibrinogen, experimental DIC rats induced by the infusion of thrombin for 1 h were submitted to microautoradiograms (MARGMs) of some major organs. The radioactivity of [125I]fibrin thrombi, which were observed as silver grains, was localized in the glomeruli and parts of small vessels in the kidney. In the liver, microthrombi were seen in sinusoid vessels and on Kupffer cells. In addition, many microthrombi were noted in small vessels in the lung and marginal zones in the spleen. Two min after the intravenous administration of [125I]t-PA to DIC rats, many silver grains were observed on each MARGM of the kidney, lung, liver and spleen showing the formation of microthrombi. From the identical results with the observations of MARGMs after the injection of [125I]fibrinogen, we confirmed that t-PA was highly accumulated to microthrombi formed in small vessels of the organs. The scattered silver grains were widely observed on the hepatocytes. This result suggested that t-PA bound to the parenchymal cell surface might be transported into the hepatocytes by receptor-mediated endocytosis. On the other hand, when [125I]urokinase plasminogen activator [( 125I]u-PA) was administered intravenously to DIC rats, many silver grains were observed on MARGM of the proximal tubules in the kidney but not seen on MARGMs of the glomeruli in the kidney, nor in the lung, liver, and spleen. This observation suggested that u-PA might not have a characteristic to accumulate to thrombi. PMID- 1907323 TI - New fluorogenic substrates containing bimane system for ribonuclease T1. AB - As a part of the development of organic fluorescent reagents, bimane derivatives were coupled to guanosine 3'-monophosphate, and they were shown to be useful fluorogenic substrates for the assay of ribonuclease T1. PMID- 1907325 TI - A comparison of two insecticidal shampoos in the treatment of head louse infection. AB - The efficacy and tolerability of a phenothrin liquid shampoo was compared with a carbaryl shampoo in 50 children with head lice infection. Twenty-five children were treated with a phenothrin liquid shampoo and 25 with a carbaryl shampoo. Each treatment was applied on three occasions at three-day intervals. Reinspection two weeks after initiation of treatment revealed two apparent treatment failures in the carbaryl group and one in the phenothrin group. No side effects were reported for either treatment. It is concluded that phenothrin liquid shampoo is a safe and effective treatment for head louse infection and is therefore a useful addition to those insecticides currently employed. PMID- 1907324 TI - Oxidative degradation of an antitumor (1-3)-beta-D-glucan, grifolan. AB - A (1-3)-beta-D-glucan, grifolan (GRN), recovered from the peritoneal cavity after 1 d from i.p. injection contained a significant amount of anionic metabolite(s) having lower Mr than the parent GRN. In parallel with this observation, GRN induced peritoneal exudate cells exhibiting a higher level of oxidative burst than the non-stimulated, resident peritoneal cells. Chemical oxidation of GRN by active oxygen species such as (a) ascorbic acid-CuSO4, (b) hydrogen peroxide, (c) hydrogen peroxide-CuSO4, or (d) hypochlorous acid also produced anionic as well as lower Mr degradation products. Under these experimental conditions the structural changes were remarkable and in the order of a less than b less than c less than d. The products formed under the conditions (a) and (b) retained significant antitumor activity but those of (c) and (d) lost the activity. However, oxidation product(s) of curdlan, an antitumor inactive (1-3)-beta-D glucan having no branch, by condition (d) induced significant antitumor activity. These results suggested that oxidative degradation of (1-3)-beta-D-glucans produced some temporary active metabolites and then gradually changed to the inactive form. However, these active metabolites contribute less than the parent glucan on the whole activation mechanisms of the host by (1-3)-beta-D-glucans. PMID- 1907326 TI - Reversible computerized tomographic lesion following childhood seizures. AB - Recently reversible computerized tomographic (CT) lesions following seizures have been reported, mostly in adult subjects. Focal CT lesions following seizures were recorded in 20 children. The distribution of the lesions was parietal in 17, frontal in two, occipital in one, and temporo-parietal in one. Multiple simultaneous lesions were observed in one child. Plain scan revealed evidence of cerebral oedema in 16 patients (mild 10, moderate four, and severe two). Enhanced scan showed a ring lesion in 12, hyperdense focus in five, and non-enhancing (hypodense) lesion in two children (excluding one child who had multiple lesions; three rings and one dense focus). These subjects were treated with anti-epileptic drugs only. Repeat CT scans yielded a complete resolution in 12 and a significant resolution in eight. It is concluded that in children with seizures, reversible CT demonstrable focal abnormalities may occur. PMID- 1907327 TI - Factors which influence child health with specific reference to nutrition in Siaya district western Kenya. PMID- 1907328 TI - Protein energy malnutrition and cerebral malaria. PMID- 1907329 TI - The effects of extracorporeal shock wave lithotripsy on renal growth, function and arterial blood pressure in an animal model. AB - The long-term effects of extracorporeal shock wave lithotripsy (ESWL*) on children treated for renal calculi are unclear. To study the long-term bio effects of this mode of treatment on the immature animal we evaluated 30 New Zealand white rabbits at 7 weeks of age for weight, serum blood urea nitrogen and creatinine, and arterial blood pressure after which they underwent left nephrectomy. Each group of 5 rabbits received ESWL of varying levels (500 to 3,000 shock waves) to the remaining right kidney using the Northgate SD3 lithotriptor (spark gap mediated). One control group received no shock waves. At maturity (16 weeks) the aforementioned parameters were measured again, and the kidneys and any grossly abnormal adjacent organs were examined. We found no significant change in total animal growth, renal growth, renal function or perirenal organs in the post-ESWL groups versus the control group. All post-ESWL groups had an increase in mean arterial blood pressure versus the control group with 3 of 6 groups showing significant increases (p less than 0.05). Histological renal changes, seen at all energy levels of ESWL delivered, included interstitial fibrosis, tubular atrophy, glomeruli destruction, capsular thickening, perivascular fibrosis and mild arteriole wall thickening. Changes were proportional to the number of shocks received. We conclude that ESWL delivered to immature animals does not significantly affect renal growth and function but it can cause significant permanent histological renal changes even at low doses and may result in an increase in adult mean arterial blood pressure. PMID- 1907330 TI - Massive cystic ureteral diverticula in infancy. AB - We report 2 cases of massive abdominal distension due to a mid ureteral diverticulum. In a 1-year-old boy the mid ureteral diverticulum was associated with an atrophied chronically scarred kidney. In a female newborn the diverticulum was associated with an upper pole ureter of a completely duplicated system. To our knowledge this type of ureteral diverticulum has not been reported previously. PMID- 1907331 TI - The effect of oxyphenonium bromide and oxybutynin hydrochloride on detrusor contractility and reflux in children with vesicoureteral reflux and detrusor instability. AB - In a prospective study the effects of the anticholinergic drugs oxyphenonium bromide and oxybutynin hydrochloride on detrusor contractility and reflux were studied. Although anticholinergic properties are claimed of both drugs, only oxybutynin hydrochloride proved to decrease detrusor contractility and the degree of reflux, probably due to a direct spasmolytic effect on the detrusor. Therefore, in cases of reflux and detrusor instability treatment with oxybutynin hydrochloride is recommended. PMID- 1907333 TI - [Thrombolytic treatment of retinal arterial occlusions with plasminogen activator]. AB - Tissue-type plasminogen activator (rt-PA), a gene-technologically manufactured fibrinolytic compound, has been employed successfully for treatment of cardial and peripheral arterial vascular occlusions. The advantage of this compound is its lytic effect. It selectively displays its effect in therapeutic dosage on fresh thrombuses, showing only minimal influence on physiological clotting as such. Two patients with stop of the retinal arterial bloodflow in videofluorescence angiography were treated with short term lysis with 100 mg rt PA, the onset of therapy was 7 and 6.5 hours after loss of vision. Already during the infusion of the compound reperfusion was achieved. Inspite of the relatively late onset of treatment, the visual fields of both patients improved. We assume lytic therapy with rt-PA to be an effective therapy for patients with retinal arterial occlusion, if applied within the first eight hours after acute loss of vision. The number of patients who could potentially benefit from this therapy is limited considering the high rate of spontaneous reperfusion before the first eye exam in 84% of the cases and considering the manifold contraindications for this therapy: 35% of the patients above 70 years of age, 56% of the patients with arterial hypertension (RR 160/100 and above) as well as 10% of the patients treated with Coumarine-derivatives should not undergo lysis. Only 43% of the patients with occlusion of central retinal artery and 21% of the patients with occlusion of retinal branch arteries received the first eye exam within the first 8 hours after the occlusion. PMID- 1907334 TI - [Computer-assisted parenteral feeding]. PMID- 1907332 TI - [Economic effectiveness of conservative and surgical methods of treatment of duodenal ulcer in young patients]. AB - The work evaluates the results of treatment of duodenal ulcer in 152 young patients. The state's financial losses connected with their treatment by various methods are counted up. Prolonged nonoperative treatment was applied in 52 patients (group I), organ-preserving operations were carried out in 100 patients (group II). Group I patients felt much worse, most of them suffered from annual recurrences of the disease, 21% underwent various operative interventions later due to the development of complications. Good and excellent results were recorded in 86% of group II patients. It was established that not only are the clinical results better in group II patients, but the economical losses in timely performance of organ-preserving operations are half those in prolonged nonoperative therapy. PMID- 1907335 TI - Different phenotypic expression of Fabry disease in female monozygotic twins. PMID- 1907336 TI - Sanfilippo B disease: a re-examination of a particular sibship after 12 years. AB - A particular sibship, with mild and severe types of Sanfilippo B disease within the same family, was re-examined after 12 years. The phenotypes of the mild and of the severe patients were maintained, specifically the mental retardation. Cultures of lymphoblasts from the mild patient were established and proteins were electrophoresed in native conditions and then immunoblotted with specific antibody. Two bands of 182,000 and 131,000 Da were found, comigrating with the enzyme from normal lymphoblasts and the enzyme from normal urine. The data are discussed in relationship to the molecular defect underlying alpha-N acetylglucosaminidase deficiency and to the ability of the antiserum to react with normal, mutant, monomeric and multimeric forms of the enzyme. PMID- 1907337 TI - A specific fluorogenic assay for N-acetylgalactosamine-4-sulphatase activity using immunoadsorption. AB - A method combining immune capture and enzyme detection by fluorochemistry has been developed for the diagnostic assay of N-acetylgalactosamine-4-sulphatase (4 sulphatase). The procedure uses a monoclonal antibody 4-S 4.1 to immunoadsorb 4 sulphatase specifically from complex protein samples containing other sulphatases, and 4-methylumbelliferyl sulphate to detect captured 4-sulphatase. The assay provides an accurate and simple method for the diagnosis of Maroteaux Lamy syndrome (Mucopolysaccharidosis type VI). PMID- 1907339 TI - To treat or not to treat, this is the real question. PMID- 1907340 TI - Gene transfer into human leukemia cell lines by electroporation: experience with exponentially decaying and square wave pulse. AB - The efficiency of gene transfer into human leukemia cell lines by electroporation was investigated. For both transient expression (beta-galactosidase gene) and stable transformation (neomycin resistance gene), the transfer efficiency into leukemia cell lines using a square wave pulse was superior to that using an exponentially decaying wave. The transfer rate of pMoZtk (containing beta galactosidase gene) into K562 by electroporation using a square wave was approximately 5%, compared with 1% by an exponentially decaying pulse. Whereas the transfer rate of pMAM-neo into K562 by electroporation using an exponentially decaying pulse was less than 10(-5), a square wave generated much more efficient introduction rate of nearly 10(-3). In the other leukemia cell lines also, some square wave yields were better than exponential yields and all square wave yields were at least as good as the exponential yields. PMID- 1907338 TI - A feasibility study of the SDI test for the evaluation of gastrointestinal cancer sensitivity to anticancer drugs. AB - The succinic dehydrogenase inhibition (SDI) test has been widely used to evaluate the sensitivity of cancer cells to anticancer agents. Recently, the techniques for tissue culture have progressed; the ability to make formazan has improved with the use of methylthiazol tetrazolium bromide (MTT) instead of triphenyl tetrazolium chloride (TTC) in this assay. Therefore, we modified the SDI test in order to evaluate the drug response to gastrointestinal cancer and applied it in a clinical study. In this assay, the optimal concentration levels of mytomycin-C and Adriamycin for the clinical materials are 10 micrograms/ml, that is, 10 times higher than for the cancer cell line, and that of Cisplatin is 30 micrograms/ml, for Cisplatin is unstable in the culture medium. To evaluate its antitumor effect, it was found necessary to expose the cancer cells to 5-fluorouracil (5 FU) for 3 days. We applied this assay for the clinical materials; the evaluable rate of this assay is 83.3%. The peculiarity of this assay is its high evaluable rate. These results suggest that this test may be useful for clinical application. PMID- 1907341 TI - Chronic lymphatic leukaemia: an investigation of HLA antigen frequencies and white cell differential counts in patients, relatives and controls. AB - Histocompatibility antigen (HLA) frequencies in chronic lymphatic leukaemia (CLL) patients and control subjects were compared with respect to disease susceptibility and prognosis. Additionally, HLA and full blood count data were compared in relatives of 25 patients and 31 controls. We found no association of HLA with susceptibility although the presence of HLA B12, alone or in combination with HLA A2, indicated better prognosis. Relatives HLA identical with the patients showed no evidence of white cell disorder when compared with haplo- or non-identical relatives, or controls. As a group, however, relatives of patients had fewer lymphocytes than relatives of controls. PMID- 1907342 TI - Laboratory diagnosis of von Willebrand's disease. AB - The laboratory diagnosis of von Willebrand's disease (vWD) has become much more difficult because of the identification of numerous variant forms of vWD. The biologic and pathologic variability in individual patients necessitates a comprehensive assessment. Patients with classic type I vWD may be easily identified by using the bleeding time, activated partial thromboplastin time, platelet count, von Willebrand antigen, and ristocetin cofactor tests. In patients with variant forms of vWD, however, multimeric analysis of both platelet and plasma von Willebrand factor may be necessary. Furthermore, more than one assessment may be needed to detect an abnormal result in many of the aforementioned tests. PMID- 1907343 TI - Treatment of von Willebrand's disease. AB - Early recognition that plasma infusions could correct the prolonged bleeding time and factor VIII deficiency in von Willebrand's disease (vWD) prompted major research efforts. Identification of the factor VIII molecule, its components, and its functions has provided critical information about replacement requirements to prevent or control bleeding. Plasma and cryoprecipitate have been the mainstay of therapy. Until recently, lyophilized coagulation factor concentrates had little usefulness in treating vWD. Current factor VIII concentrates prepared by monoclonal or recombinant technology (or both) are devoid of von Willebrand factor. Desmopressin has been a revolutionary synthetic agent useful in numerous patients with mild or moderately severe vWD. In many patients, however, desmopressin is ineffective. Only a few currently available factor VIII concentrates contain biologically active von Willebrand factor and can be used to prepare patients for surgical procedures or to stop hemorrhage. Inhibitors of von Willebrand factor arise de novo or in patients with vWD. Management with activated prothrombin complex concentrates or removal of antibody with protein A columns has been successful. Despite current technologic advances, not all patients with vWD can be successfully treated. Many problems with vWD continue to be unresolved. PMID- 1907345 TI - Presence of human immunodeficiency virus DNA in laser smoke. AB - Concentrated tissue culture pellets infected with human immunodeficiency virus (HIV) containing 1 x 10(7) cells/ml were vaporized by means of a carbon dioxide laser. The vaporous debris resulting from the laser's impact were evacuated through sterile silastic tubing, then bubbled through sterile culture medium (RPMI) positioned in series with a commercial smoke evacuator. No HIV DNA was detected in the culture medium flask. Tissue culture studies of the silastic collection tubing revealed p24 HIV gag antigen in 3 of 12 tube segments at the end of 1 week and in 1 of 12 tube segments at 2 weeks. No sustained infection of HIV cultured cells was observed at the 28th day. Polymerase chain reaction (PCR) analysis of particulate debris obtained from the silastic collection tubing was positive from proviral HIV DNA in both immediately sampled and day 14 cultured material. PMID- 1907344 TI - Structure and function of von Willebrand factor: relationship to von Willebrand's disease. AB - This review summarizes the current knowledge of the structure and function of von Willebrand factor and of the pathophysiologic features, diagnosis, classification, and treatment of von Willebrand's disease, the most common congenital bleeding disorder in humans. Specific regions of the von Willebrand factor subunit that are of functional importance have been identified. The structure of these functional domains of von Willebrand factor, as known to date, is described. A classification of von Willebrand's disease, based on the definition of structural and functional abnormalities of the molecule and initial characterization of genetic mutations, is discussed. With more precise characterization of molecular abnormalities, more selective therapeutic intervention for specific subtypes of von Willebrand's disease should eventuate. PMID- 1907346 TI - Diabetes prevention in BB rats by inhibition of endogenous insulin secretion. AB - Chronic prophylactic exogenous insulin treatment commenced in young diabetes susceptible BB rats has been shown to prevent type I diabetes. This study was undertaken to examine whether this diabetes protection resulted from inhibition of beta-cell insulin secretion by exogenous insulin administration or from either a metabolic (chronic hypoglycemia) or immune effect of this treatment. We compared the effects of prophylactic exogenous insulin treatment with those of an insulin secretion inhibitor, diazoxide, an oral hypoglycemic agent, glyburide, and, water alone as controls in randomly divided BB diabetes-prone littermates treated from age 30 to 150 days. These experiments confirmed that exogenous insulin can prevent type I diabetes in the BB rat. Diazoxide, which inhibits endogenous insulin secretion while causing hyperglycemia (rather than hypoglycemia with insulin), also offered protection from diabetes. In contrast, the oral hypoglycemic agent glyburide, which increased insulin secretion, but decreased plasma glucose during the early part of the experiment, did not affect the incidence of diabetes. The lymphocyte subpopulations were unaffected by these treatments. These data support the hypothesis that decreased beta-cell activity is responsible for the protection against the immune beta-cell destruction. PMID- 1907347 TI - Effects of hyperinsulinemia and hyperglycemia on insulin receptor function and glycogen synthase activation in skeletal muscle of normal man. AB - Insulin receptor function, glycogen synthase activity, and activation by phosphatases were studied in biopsies of human skeletal muscle under conditions of hyperglycemia and/or hyperinsulinemia for 150 minutes. Twenty-one healthy volunteers underwent either (A) a hyperinsulinemic, euglycemic clamp (serum insulin, 160.0 +/- 7.7 mU/L; plasma glucose, 4.9 +/- 0.1 mmol/L; n = 9), (B) a hyperglycemic clamp during normoinsulinemia (serum insulin, 18.1 +/- 3.3 mU/L; plasma glucose, 12.9 +/- 0.2 mmol/L; n = 6), or (C) a combined hyperinsulinemic, hyperglycemic clamp (serum insulin, 158.3 +/- 15.0 mU/L; plasma glucose, 11.4 +/- 0.8 mmol/L; n = 6). During all studies, the endogenous insulin secretion was inhibited with somatostatin. Insulin binding and kinase activity of insulin receptors solubilized from vastus lateralis muscle biopsies were unaffected by hyperglycemia and/or hyperinsulinemia. Hyperinsulinemia activated the muscle glycogen synthase with a decrease in the half-maximal activation constant (A0.5) for glucose-6-phosphate (G6P) from 0.53 +/- 0.04 to 0.21 +/- 0.02 mmol/L (study A, P less than .02) and from 0.53 +/- 0.06 to 0.19 +/- 0.05 mmol/L (study C, P less than .03). In addition, the rate of glycogen synthase activation by phosphatases increased from 0.078 +/- 0.017 to 0.134 +/- 0.029 U/min/mg protein (study A, P less than .03) and from 0.082 +/- 0.013 to 0.145 +/- 0.033 U/min/mg protein (study C, P = .05). Hyperglycemia during normoinsulinemia did not affect A0.5 or phosphatase activity. In conclusion, (1) hyperinsulinemia for 2 1/2 hours increases glycogen synthase activity and activation by phosphatases independently on the glycemia; and (2) insulin receptor binding and basal and insulin stimulated receptor kinase activity are not modified during short-term hyperinsulinemia and/or hyperglycemia. PMID- 1907349 TI - Effects of a brain-enhanced estrogen delivery system on tail-skin temperature of the rat: implications for menopausal hot flush. AB - The menopause results from the decreasing production of ovarian estrogens/progestins. This loss of ovarian hormones in 75-85% of women leads to a number of brain-mediated steroid-withdrawal symptoms, the most frequent being hot flushes. Thus, replacement therapy with a brain-enhanced estrogen delivery system (E2-CDS) with sustained release of estradiol (E2) in the brain may be more effective in the treatment of menopausal symptoms than currently used estrogens. The present study was designed to evaluate the effects of E2-CDS vs. E2, on the tail-skin temperature (TST) surge associated with administration of naloxone to morphine-dependent rats, an animal model for menopausal hot flush. Ovariectomized rats received a single or multiple doses of E2-CDS at 1.0 mg/kg body weight or E2 (0.5 mg pellet) weekly for 1 or 3 weeks before temperature recording. The mean maximal elevation in TST of the control animals was 6.4 +/- 0.2 degrees C. A single injection of E2-CDS attenuated the naloxone-induced rise in TST by 25%, while multiple injections resulted in significant attenuation of the rise in TST (3.4 +/- 0.6). By contrast, multiple implants of E2 pellet (3 pellets over 3 weeks) did not affect the surge of TST. Plasma E2 levels in animals treated with E2-CDS were slightly increased to 13 pg/ml for single-injected and to 44 pg/ml for multiple-injected rats. However, the E2-pellet treatment produced plasma E2 levels that were 2-fold greater than the E2 levels produced by multiple injections of E2-CDS. Plasma gonadotropins (LH and FSH) were significantly suppressed with the E2-pellet as well as the single and multiple E2-CDS treatment. Plasma prolactin levels were significantly elevated by E2 pellet and multiple injections of E2-CDS. The kinetic profiles of E2-CDS metabolites in plasma indicated an apparent t1/2 = 8 h for E2-Q+ and 3 h for E2. Collectively, these data support the view that E2-CDS may be potentially useful in the treatment of vasomotor hot flushes. PMID- 1907348 TI - Cyclic fluctuations in human serum lipid and apolipoprotein levels during the normal menstrual cycle: comparison with changes occurring during oral contraceptive therapy. AB - The influence of menstrual cycle phases and hormonal contraception on serum lipid and apolipoprotein (apo) levels was investigated in a group of normally menstruating young women. The study period covered a normal menstrual cycle (pretherapy), the fourth cycle of treatment with a triphasic oral contraceptive (OC) preparation, and the cycle immediately following interruption of therapy (cycle 5, posttherapy). Cycle phases were defined on the basis of serum hormone levels and basal body temperature determinations. Significant differences in cholesterol (free and esterified) levels were observed during the menstrual phase of both the normal menstrual cycle (lower) and the OC cycle (higher), when compared with the other phases. Triglycerides, which were higher under OCs, fluctuated similarly throughout the two cycles, but phase differences did not reach statistical significance. Apo AI and apo B were both higher under OCs, and apo B followed a trend similar to cholesterol during the two cycles. During the first month after discontinuation of OCs, cholesterol levels returned progressively to baseline values, while triglycerides were only partially decreased. We conclude that cyclic fluctuations in lipid levels do occur under the influence of both endogenous and exogenous sex hormones. PMID- 1907350 TI - [The adhesion of microorganisms to metal-containing carbon sorbents]. PMID- 1907352 TI - Comutagenic and coclastogenic effects of selenium in vitro and in vivo. AB - The comutagenic activity of selenium was investigated using in vitro and in vivo techniques, including the liquid suspension modification of the standard Salmonella/microsome mutagenicity assay, the metaphase analysis of chromosome aberrations in CHO cells and in mouse bone marrow as well as the micronucleus assay in mouse bone marrow. 4 h growth of S. typhimurium TA1535 in a nutrient broth containing 2.9 x 10(-5) M but not 1.16 x 10(-5) M Na2SeO3 caused an up to 10-fold increase of the number of N-methylnitrosourea (MNU, 2.0-2.5 mM)-induced his+ revertants and an up to 2-fold elevation of N-methyl-N'-nitro-N nitrosoguanidine (MNNG, 1.48 x 10(-5))-induced mutation rate. Pretreatment of bacteria with Na2SeO3 alone had no effect on the spontaneous mutation level. The combined treatment of CHO cells with MNNG (1.25 x 10(-5) M) or tobacco smoke (TS, 2-3 puffs generated by a cigarette inhalation machine) plus Na2SeO3 (0.58-1.16 x 10(-5) M) starting 2 h and 4 h before the MNNG or TS treatment respectively resulted in a 2-3-fold increase in the percent of metaphases with chromosome aberrations. Furthermore, treatment for 7-14 days of male BDF1 (C57Bl x DBA2) or CC57W mice with Na2SeO3, added to the drinking water at a concentration of 10 ppm, potentiated by 2-3 times the chromosome-damaging activity of urethane (0.5 1.0 g/kg, i.p.) in mouse bone marrow, as measured by the formation of micronuclei or chromosome aberrations. In addition, Na2SeO3 increased up to 43.8% the number of micronucleated polychromatic erythrocytes (MNPCE) induced by mitomycin C (MMC, 1.5 mg/kg, i.p.) in BDF1 mouse bone marrow. Treatment of mice with Na2SeO3 alone had no effect on the spontaneous level of MNPCE. All these findings are consistent with a comutagenic and coclastogenic activity of selenium both in prokaryotes and in eukaryotes, in vitro as well as in vivo after pretreatment of target cells with the trace element. PMID- 1907351 TI - Enhancer mediated suppression of epsilon heavy-chain gene expression in a murine IgE-producing hybridoma. AB - In vitro co-culture of IgE-secreting hybridoma cells (B53) with spleen cells harvested from mice with established B53 tumours results in a specific, T cell dependent suppression of epsilon-chain expression in the B53 cells. The role of immunoglobulin enhancers in the suppression of IgE synthesis in B53 cells was examined by transfecting B53 cells with CAT expression vectors containing the immunoglobulin heavy- or kappa light-chain intron enhancers or a Rous sarcoma virus (RSV) LTR. When epsilon-chain expression of transfected cells was suppressed in vitro. CAT expression was also suppressed in cells transfected with vectors containing the immunoglobulin heavy-chain gene enhancer, but not in cells transfected with vectors containing the kappa enhancer or RSV LTR. Thus, the T cell-dependent suppression of IgE synthesis in B53 cells correlates with a specific inactivation of the immunoglobulin heavy chain enhancer, strongly suggesting that T cell-mediated suppression of Ig synthesis can normally occur through specific repression of Ig enhancer function. This represents a new regulatory pathway involved in the control of IgE synthesis and is the first indication that the enhancer mediated expression of Ig genes in B cells can be modulated through T cell-dependent processes. PMID- 1907353 TI - Quantitative analyses of the induction of chromosome aberrations and sister chromatid exchanges in human lymphocytes exposed to gamma-rays and mitomycin-C in combination. AB - Most chemicals are S-dependent and are potent inducers of SCE, but do not produce chromosome-type aberrations in the first metaphases after exposure. Ionizing radiation, which is an S-independent agent, produces chromosome-type aberrations, especially dicentrics and rings, but inefficiently produces chromatid-type aberrations. A series of experiments has been performed to investigate whether cytogenetic damage induced by ionizing radiation (gamma-rays) might be assessed separately from that induced by the alkylating chemical, mitomycin C (MMC), when human lymphocytes were exposed to these 2 agents in combination. Whole-blood cultures of human lymphocytes in G0 phase were exposed to gamma-rays and MMC in combination or separately. Cytogenetic analyses were done for both chromosome aberrations (CA), analyzed in cultures incubated for 56 h without BrdUrd, and sister-chromatid exchanges (SCEs) in cultures incubated for 72 h with BrdUrd. The frequency of chromosome-type aberrations (dicentrics and rings) increased with increasing doses of gamma-rays from 0.5 to 4.0 Gy. The dose-response relationships were the same with or without concomitant treatment with MMC (10( 6) M). Although the SCE frequency increased with increasing doses of MMC, the increase was nearly the same as when cells were treated with both MMC and gamma rays (2 Gy). There was no interaction between MMC and gamma-rays concerning these 2 endpoints. PMID- 1907354 TI - Prevention of HIV-1 IIIB infection in chimpanzees by CD4 immunoadhesin. AB - The first step in infection by the human immunodeficiency virus (HIV) is the specific binding of gp120, the envelope glycoprotein of HIV, to its cellular receptor, CD4. To inhibit this interaction, soluble CD4 analogues that compete for gp120 binding and block HIV infection in vitro have been developed. To determine whether these analogues can protect an uninfected individual from challenge with HIV, we used the chimpanzee model system of cell-free HIV infection. Chimpanzees are readily infected with the IIIB strain of HIV-1, becoming viraemic within about 4-6 weeks of challenge, although they do not develop the profound CD4+ T-cell depletion and immunodeficiency characteristic of HIV infection in humans. CD4 immunoadhesin (CD4-IgG), a chimaeric molecule consisting of the N-terminal two immunoglobulin-like regions of CD4 joined to the Fc region of human IgG1, was selected as the CD4 analogue for testing because it has a longer half-life than CD4, contributed by the IgG Fc portion of the molecule. In humans, this difference results in a 25-fold increased concentration of CD4-IgG in the blood compared with recombinant CD4. Here we report that pretreatment with CD4-IgG can prevent the infection of chimpanzees with HIV-1. The need for a preventative agent is particularly acute in perinatal HIV transmission. As recombinant CD4-IgG, like the parent IgG molecule, efficiently crosses the primate placenta, it may be possible to set up an immune state in a fetus before HIV transfer occurs, thus preventing infection. PMID- 1907355 TI - The high cost of failure. Prisoners with and without HIV infection. PMID- 1907356 TI - [Faster treatment of acute myocardial infarct by administration of alteplase (rt PA) prior to hospitalization]. PMID- 1907357 TI - [Intensive care for newborn infants: a needs assessment]. PMID- 1907358 TI - Productivity and cost-effectiveness measures: factors in decision making. PMID- 1907359 TI - The physician and the poor. PMID- 1907360 TI - Leaving a loved one in untrained hands. PMID- 1907361 TI - In vitro DNA binding activity of Fos/Jun and BZLF1 but not C/EBP is affected by redox changes. AB - The leucine zipper family of proteins have a DNA binding domain composed of a leucine zipper dimerisation interface and a basic DNA binding structure. We show here that redox changes affect the in vitro DNA binding ability of a select subset of leucine zipper proteins. The bacterially expressed DNA binding domains of Fos/Jun and BZLF1 are unable to bind DNA under non-reducing conditions whereas binding of the C/EBP DNA binding domain is unaffected. Sensitivity to redox state is due to the presence of a conserved cysteine residue in the basic DNA binding motif of Fos, Jun and BZLF1 but not C/EBP. Under non-reducing conditions an intermolecular disulphide bridge is formed between the cysteine residues of each basic motif within a dimer, which prevents DNA binding. We show that oxidation of these C residues can be achieved enzymatically, using glutathione peroxidase, and that DNA binding protects them from oxidation. These data raise the possibility that intracellular changes in the redox state may differentially regulate the activity of leucine zipper family members. In addition the loss of DNA binding activity under non-reducing conditions has implications for the purification methods used to isolate proteins of the leucine zipper family for structural analysis. PMID- 1907362 TI - Morphine-6-glucuronide: effects on ventilation in normal volunteers. AB - The respiratory responses to intravenous morphine sulphate (0.12 mg/kg), morphine 6-glucuronide (M6G: 0.03 mg/kg) and placebo were assessed in 6 healthy volunteers, using a single blind randomised crossover design. Five of these subjects underwent an additional study of M6G at 0.06 mg/kg. Respiratory rate, minute volume and end-tidal CO2 were continuously measured using a low resistance non-rebreathing circuit, a mass spectrometer and a dry gas meter. The ventilatory responses to CO2 exposures (5.5% for 4 min) were assessed 40 and 20 min before, and 20, 40 and 80 min after drug administration. Following placebo and M6G (at both doses) no change in end-tidal CO2 occurred whilst the subjects were breathing air, whereas following morphine a significant rise was seen (P less than 0.05). Morphine reduced the ventilatory response to 5.5% CO2 at all times tested (P less than 0.05) and M6G (at both doses) reduced the response to CO2 at 20 and 40 min after administration, but to a lesser degree than did morphine (P less than 0.05). PMID- 1907363 TI - Kwashiorkor: the hypothesis that incriminates aflatoxins. PMID- 1907364 TI - Antiretroviral treatment for children with human immunodeficiency virus infection. PMID- 1907366 TI - Analysis of chromosomal replicons in early embryos of Drosophila melanogaster by two-dimensional gel electrophoresis. AB - Chromosomal DNA replication units in early embryos of D.melanogaster were studied using two-dimensional gel replicon mapping techniques. DNA was prepared from nuclei encapsulated into agarose beads. This method substantially improved preservation of replication intermediates more than standard DNA preparation methods, and allowed us to detect replication intermediates for even single-copy chromosomal regions without their selective enrichment. Analysis with tandem repeats of histone genes indicated that DNA replication initiates at multiple locations on the repeating unit. The initiation sites were not localized to a defined site, but rather distributed throughout the repeating unit. DNA replication on a single-copy chromosomal region was also suggested to initiate at numerous sites, probably with little regard for the specific DNA sequences. PMID- 1907365 TI - The tyrosinase-related protein-1 gene has a structure and promoter sequence very different from tyrosinase. AB - We have determined the exon structure of the mouse tyrosinase-related protein-1 (TRP-1) gene. The gene is only 15kb in length, but contains seven introns, in contrast to the tyrosinase gene which is almost 100kb long with only four introns. Only two introns are located in homologous positions in both genes. Intron I of TRP-1 has three alternative 5' splice sites clustered within 21bp, which all splice to the same 3' site. Intron V has a very unusual 5' splice site, which has the dinucleotide GC rather than the conventional GT. We show that as little as 370bp of 5'-flanking DNA is sufficient to direct cell-specific expression of the chloramphenicol acetyl transferase gene. The flanking DNA of TRP-1, unlike tyrosinase, does not contain a TATA box or a CCAAT box. Both mouse genes, however, share an 11bp sequence, also found in human tyrosinase, which we suggest may be a melanocyte-specific promoter element. PMID- 1907367 TI - Random-primed cDNA synthesis facilitates the isolation of multiple 5'-cDNA ends by RACE. PMID- 1907368 TI - Childhood scleromyositis: an overlap syndrome associated with PM-Scl antibody. AB - Fourteen patients with childhood scleromyositis followed from 1 to more than 10 years experienced concomitant sclerodermoid and dermatomyositis features, variably expressed at one time or another during the course of the disease. The most characteristic features were myalgia-myositis, arthralgia-arthritis, puffy, atrophic, sclerotic fingers, and Raynaud's phenomenon. This overlap syndrome was the most frequent sclerodermoid condition in children, differing from both systemic scleroderma and dermatomyositis. The course of the disease was protracted and rather benign, and PM-Scl antibody was an important diagnostic and prognostic marker. We present criteria for diagnosis of scleromyositis and its differentiation from systemic scleroderma, dermatomyositis, and Sharp overlap syndrome. PMID- 1907369 TI - Immunologic markers of systemic scleroderma in children. AB - This study was performed on seven children with systemic scleroderma, three with the diffuse and four with the limited type. All three patients with diffuse scleroderma had high titers of clumpy pattern antinucleolar antibody on HEp-2 cells. The course of the disease was severe, and two children died. Four children with limited scleroderma had mild disease, and Scl-70 antibody, an immunologic marker that in adults is associated mostly with diffuse scleroderma. In one child Scl-70 antibody and anticentromere antibody coexisted, although previously the two were believed to be mutually exclusive. This study shows that limited scleroderma of childhood with slight cutaneous involvement may be associated with the Scl-70 marker. The findings in 10 adults in whom Raynaud's phenomenon developed in childhood and indurations appeared some years later, point to the significance of careful observation of these children, with repeated testing for immunologic markers of SSc. An important new finding is the association of different types of systemic sclerodermas with specific immunologic markers. PMID- 1907370 TI - Macromelanosomes as morphologic markers in childhood neurofibromatoses. PMID- 1907371 TI - A stimulatory GDP/GTP exchange protein for smg p21 is active on the post translationally processed form of c-Ki-ras p21 and rhoA p21. AB - We have purified a stimulatory GDP/GTP exchange protein for smg p21A and -B, ras p21-like small GTP-binding proteins (G proteins), cloned its cDNA, and named it GDP dissociation stimulator (smg p21 GDS). We show here that smg p21 GDS is active not only on smg p21A and -B but also on c-Ki-ras p21 and rhoA p21, all of which are post-translationally processed. Furthermore, we show that smg p21 GDS is inactive on the post-translationally unprocessed form of these proteins and on the post-translationally unprocessed form of c-Ha-ras p21 and smg p25A. All of the small G proteins recognized by smg p21 GDS have a cDNA-predicted C-terminal "CAAX" motif (where C is cysteine, A is an aliphatic amino acid, and X is any amino acid) and a polybasic region upstream of this motif. These results suggest that smg p21 GDS is at least active on a group of small G proteins having these unique C-terminal structures. Moreover, they suggest that the C-terminal post translational processing of these small G proteins, by farnesylation or geranylgeranylation of the C-terminal cysteine residue, removal of amino acids in positions denoted "AAX", and carboxyl methylation of the exposed cysteine residue, is important for the smg p21 GDS action. PMID- 1907373 TI - Avian osteoclasts as estrogen target cells. AB - Although in vivo effects of 17 beta-estradiol (estrogen) on bone turnover have been shown to occur mainly through influences on osteoclast-mediated bone resorption, the mechanism by which estrogen reduces bone resorption is unclear. To approach this question, we have examined authentic osteoclasts for evidence of a direct osteoclast response to estrogen in vitro. Highly purified (greater than (90%) viable avian osteoclasts from birds maintained on a low calcium diet were obtained using an osteoclast-specific monoclonal antibody coupled to magnetic beads. Isolated cells were either analyzed directly for estrogen receptor (ER) levels or cultured to assess the biological effects of estrogen. Northern blot analysis revealed a 5.2-kilobase mRNA that hybridized with a cDNA to human ER mRNA in the osteoclasts. An anti-human ER antibody recognized proteins of 66 kDa and 140 kDa in osteoclast extracts by Western blot analysis. The 66-kDa size is in close agreement with the reported size of the human ER. Nuclear binding of estrogen to intact viable osteoclasts was steroid-specific and saturable, with 5662 +/- 1420 molecules bound per nucleus (mean +/- SEM). In vitro estrogen responses in osteoclasts included a dose-dependent decrease in resorption as well as an increase in nuclear protooncogene mRNA levels. These observations indicate that osteoclasts are capable of directly responding to estrogen in vivo. PMID- 1907372 TI - Mutations in 16S rRNA that affect UGA (stop codon)-directed translation termination. AB - Site-directed mutagenesis was performed on a sequence motif within the 3' major domain of Escherichia coli 16S rRNA shown previously to be important for peptide chain termination. Analysis of stop codon suppression by the various mutants showed an exclusive response to UGA stop signals, which was correlated directly with the continuity of one or the other of two tandem complementary UCA sequences (bases 1199-1204). Since no other structural features of the mutated ribosomes were hampered and the translation initiation and elongation events functioned properly, we propose that a direct interaction occurs between the UGA stop codon on the mRNA and the 16S rRNA UCA motif as one of the initial events of UGA dependent peptide chain termination. These results provide evidence that base pairing between rRNA and mRNA plays a direct role in termination, as it has already been shown to do for initiation and elongation. PMID- 1907375 TI - Expression of the human apolipoprotein A-I gene in transgenic mice alters high density lipoprotein (HDL) particle size distribution and diminishes selective uptake of HDL cholesteryl esters. AB - Transgenic mice carrying the human apolipoprotein (apo) A-I gene (HuAITg mice) were used to examine the effects of overexpression of the human gene on high density lipoprotein (HDL) particle size distribution and metabolism. On a chow diet, control mice had HDL cholesterol and apo A-I levels of 49 +/- 2 and 137 +/- 12 mg/dl of plasma, respectively. HuAITg mice had HDL cholesterol, human apo A-I, and mouse apo A-I levels of 88 +/- 2, 255 +/- 19, and 16 +/- 2 mg/dl, respectively. Nondenaturing gradient gel electrophoresis revealed control mouse plasma HDL to be primarily monodisperse with a particle diameter of 10.2 nm, whereas HuAITg mouse plasma HDL was polydisperse with particles of diameter 11.4, 10.2, and 8.7 nm, which correspond in size to human HDL1, HDL2, and HDL3, respectively. In vivo turnover studies of HDL labeled with [3H]cholesteryl linoleyl ether (representing the cholesteryl ester pool) and 125I-apo A-I were performed. In control animals, the fractional catabolic rate (FCR) for HDL cholesteryl ester (0.197 +/- 0.010 pool/hr) was significantly (P less than 0.0005) more than the apo A-I FCR (0.118 +/- 0.006 pool/hr). In the HuAITg mice, the HDL cholesteryl ester FCR (0.124 +/- 0.008 pool/hr) was the same as the apo A I FCR (0.126 +/- 0.010 pool/hr). There were no significant differences between control and HuAITg animals in the sites of tissue removal of HDL cholesteryl ester, with the liver extracting most of the injected radioactivity. Control and HuAITg animals had comparable liver and intestinal cholesterol synthesis and LDL FCR. In conclusion, HuAITg mice have principally human and not mouse apo A-I in their plasma. This apparently causes a change in HDL particle size distribution in the transgenic mice to one resembling the human pattern. The replacement of mouse by human apo A-I also apparently causes the loss of the selective uptake pathway of HDL cholesteryl esters present in control mice. These data imply that apo A-I primary structure has a profound influence on HDL particle size distribution and metabolism. PMID- 1907374 TI - Altered antigen receptor signaling in anergic T cells from self-tolerant T-cell receptor beta-chain transgenic mice. AB - T-cell tolerance to the minor lymphocyte-stimulating antigen Mls-1a in a T-cell receptor (TcR) V beta 8.1 transgenic line of mice is maintained by both clonal deletion and clonal anergy. Approximately 20-50% of peripheral CD4+ (but not CD8+) T cells isolated from these mice are anergic and fail to proliferate following TcR ligation. We have examined key events in T-cell signaling in peripheral T cells isolated from these mice. In this report, we show that the anergic CD4+ T cells did not mobilize calcium or express receptors for interleukin 2 (IL-2) following TcR ligation. However, the cells retained viability and functional potential because stimulation with phorbol 12-myristate 13-acetate and ionomycin bypassed the block in receptor-mediated signaling and induced IL-2 receptor expression and proliferation of the anergic cells. PMID- 1907376 TI - Dosage compensation of the Drosophila pseudoobscura Hsp82 gene and the Drosophila melanogaster Adh gene at ectopic sites in D. melanogaster. AB - Measurements were made of the amounts of larval RNA transcribed from the autosomal Adh gene of Drosophila melanogaster and the X chromosomal Hsp82 gene of Drosophila pseudoobscura carried on the same P-element transposon inserted at various sites in the D. melanogaster genome. Both genes were fully compensated at sites in euchromatic regions of the X chromosome but neither was compensated at a site in the centric beta-heterochromatin of the X chromosome. No compensation of the D. pseudoobscura Hsp82 gene was found at any of 10 autosomal insertion sites tested. The compensation behavior of the transposed genes was, therefore, not determined by closely linked sequences but instead was determined in each case by their new chromosomal environment. PMID- 1907377 TI - Analysis of the enhancer element that controls expression of sevenless in the developing Drosophila eye. AB - The sevenless gene encodes a protein-tyrosine kinase receptor expressed in a complex pattern during the development of the Drosophila melanogaster eye. We have previously shown that this pattern is regulated transcriptionally by an enhancer located in the body of the sevenless gene. Here we extend our analysis of the sevenless enhancer, defining a 475-base-pair fragment that contains elements necessary for the correct qualitative and quantitative expression of the sevenless gene. Within this fragment are sequence elements conserved in the sevenless gene of a distantly related Drosophila species and protected from DNase I digestion by nuclear extracts isolated from adult heads and imaginal discs. Partial deletions of the 475-base-pair fragment result in preferential loss of expression in different subsets of cells. These results suggest that the normal pattern of expression is generated by the combined action of separate cell specific regulatory elements. PMID- 1907378 TI - Modulation of keratinocyte biology by gamma interferon: relevance to cutaneous wound healing. PMID- 1907380 TI - Pediatric thoracic surgery. PMID- 1907381 TI - Unusual varieties of diaphragmatic herniae. AB - Unusual varieties of diaphragmatic herniae can be classified into two major groups, congenital and acquired. The late-presenting Bochdalek herniae often present difficulties in diagnosis which may lead to inappropriate treatment. The prime example is the herniated stomach, which is mistaken for a tension pneumothorax. Strangulation is a rare, but an important, complication of Bochdalek herniae. A number of techniques for closure of large diaphragmatic defects are described with recommendation of those procedures which can be performed rapidly and effectively in a critically ill infant. The literature concerning eventration is confusing due to different definitions of the condition by different authors. It may be difficult to distinguish preoperatively between this condition and congenital diaphragmatic hernia with a sac. Such distinction is often not important as the decision for intervention is based on evaluation of clinical and radiological considerations. The majority of Morgagni herniae are asymptomatic and only rarely does strangulation supervene. There is a small group of infants with Morgagni hernias who present in early infancy with respiratory symptoms. Paralysis of the diaphragm due to phrenic nerve palsy recovers spontaneously in the majority of patients. The selective use of diaphragmatic plication for this condition is widely accepted, but the decision and appropriate timing for surgical intervention is often difficult. The results of surgery are very good both in the early postoperative period and also on long-term follow-up. The diagnosis of traumatic diaphragmatic hernia is often overlooked in the presence of other major injuries. The danger of strangulation of contents of this hernia is ever present and repair should be undertaken without delay once the diagnosis is made. PMID- 1907379 TI - Thyroid releasing hormone test in schizophrenic patients with post-psychotic depression. AB - 1. TSH response to TRH was assessed in 25 patients meeting operationalized criteria for the post-psychotic depression syndrome and in an age and sex matched control group of 34 primary depressed patients. 2. A blunted TSH response was observed in 36% of the patients with post-psychotic depression. 3. The rate of blunted TSH response was similar for patients with secondary post-psychotic depression to those patients with primary depressions. 4. Demographic and clinical parameters did not distinguish those post-psychotic depressed patients who had a blunted response from those who did not. 5. A blunted TSH response to TRH did not predict which patients were more likely to have a favorable response when adjunctive imipramine was added to their on-going fluphenazine decanoate and benztropine regimen. PMID- 1907382 TI - An approach to the management of chest wall deformities. AB - Chest wall deformities are seen frequently in children and adolescents. Fortunately, the deformity is usually mild and the only therapeutic requirement is patient and family reassurance. If the deformity is more severe, consideration must be given to surgical correction. Although sophisticated studies have shown that cardiopulmonary function may be limited by funnel chest, the findings are rarely of clinical significance and, therefore, with few exceptions, operations will be performed for cosmetic and/or psychological reasons. In order to be able to manage patients with chest wall deformities appropriately, clarity of thinking is essential in relation to classification, symptomatology and treatment options. Before reaching a final decision regarding operation, several interviews may be required. In order to assess the final result, long-term follow-up is mandatory. PMID- 1907383 TI - Unusual problems in oesophageal surgery in childhood. AB - Unusual problems in oesophageal surgery in childhood include problems seen both frequently and infrequently. The former includes oesophageal atresia, peptic oesophagitis and corrosive oesophagitis; the latter includes such conditions as neonatal rupture of the oesophagus, explosive rupture of the oesophagus, achalasia of the cardia, pharyngo-oesophageal fibromatosis, nasogastric intubation stricture and stricture in the immunologically compromised patient. Examples of all of these conditions have been presented and reference has also been made to a wide variety of other conditions which have been reported in the literature. Because diagnostic delay is relatively common it is important for the paediatric surgeon carefully to evaluate the symptom of dysphagia when it is present and appreciate the fact that although organic disease in childhood is relatively uncommon there are many conditions which demand diagnosis and appropriate treatment. PMID- 1907384 TI - Magnetic resonance imaging as a new diagnostic criterion in paediatric airway obstruction. AB - Magnetic resonance imaging of the trachea was performed in 21 children with congenital or acquired narrowing of the trachea or main bronchi. Diagnosis included aortic arch anomalies, innominate artery compression, pulmonary artery compression and tracheomalacia. All patients were examined after bronchoscopy. The demonstration of the trachea and the surrounding tissue and vessels on MR images enables the cause of tracheal compression and the degree and location of collapse to be evaluated. MRI is a modality well suited to characterizing tracheal narrowing without employing ionizing radiation or intravenous contrast medium. All MRI examinations were carried out with the patient under general anaesthesia so as not to risk pulmonary deterioration during sedation. In the cases presented MRI is the diagnostic step of choice after tracheobronchoscopy and broadens the diagnostic potential in extrinsic tracheal or bronchial stenosis in paediatric patients. PMID- 1907385 TI - Tracheal stenosis by innominate artery compression in infants: surgical treatment in 35 cases. AB - This is a report on 35 cases of innominate artery compression of the trachea and its surgical correction by means of aortotruncopexy. Diagnostic procedures of choice were tracheoscopy and magnetic resonance imaging, which offers representative images of inspiration and expiration, shows the anatomical relations between aortic arch and trachea and reveals the extent of tracheal compression. Surgical treatment is indicated if narrowing of the tracheal lumen exceeds 70%. By fixation of the aortic arch and the proximal innominate artery to the back of the sternum, tracheal compression is relieved. There was no unsuccessful operation in the 35 children. One late death occurred from cardiac failure, unrelated to tracheal compression. PMID- 1907386 TI - Indication and results of thoracic surgical procedures in premature infants. AB - This analysis concerns three groups of malformations: Congenital diaphragmatic hernia, patent ductus arteriosus, and oesophageal atresia. We registered a total mortality rate for all congenital diaphragmatic hernias and defects of 28.5%; the rate in full-term neonates was 27.6% and in premature infants 33.6%. Of 65 infants with a patent ductus arteriosus and a birth weight less than 1500 g, 14 died (21.5%). In most cases death was caused by sepsis. Among the 159 patients with oesophageal atresia who were treated in our hospital, 58 were premature infants. During the last 20 years, the total mortality rate among our patients was 28.9%. We had a mortality rate of 44.8% in premature infants and of 19.8% in full-term neonates. An analysis of the last 10 years showed a survival rate of 97% in healthy infants (group A in Waterston's classification). In group C, the most disadvantageous group (premature infants, severe anomalies), the rate was 61%. PMID- 1907387 TI - Nursing perspectives in the management of infants and children requiring thoracic surgery. AB - Nurses who care for infants and children undergoing thoracic surgery must function and make decisions which take into account a multiplicity of complex data. This necessitates a background of knowledge, skill and intuition which guides their nursing practice. The principles of holistic care in which the total needs of the infant and child are met within the context of the family are seen as an important approach to patient care. Selected perspectives in the care of infants with congenital and acquired thoracic anomalies are discussed, in particular infants with congenital diaphragmatic hernia and oesophageal atresia. The preparation of children for chest surgery and the postoperative nursing management are outlined and include aspects of pain management, physiotherapy and chest drain care. PMID- 1907388 TI - Progress in pediatric surgery. Historical aspects. AB - Although thoracic afflictions may be traced to the prehistoric age, successful thoracic surgery was a development of the late nineteenth and early twentieth centuries. From 1543 to 1661, Vesalius, Servetus, Harvey and Malpighi established the dynamic anatomy of the pulmonary system. Boyle, Hooke, Black and Lavoisier elaborated upon the respiratory gases between 1660 and 1794. Although the drainage of empyema had been known since Hippocratic times, the underwater seal drainage bottle to prevent pneumothorax was not invented until 1872. At the turn of the century, Sauerbruch delayed the development of thoracic surgery for 30 years by opposing the use of positive pressure ventilation, which had not only been known to the ancients but also in clinical practice since the mid-1800s. Once positive pressure ventilation was established, routine successful thoracic surgery still had to await the development of safe blood transfusion by Landsteiner (1900, 1940) and the availability of antibiotics discovered by Chain, Florey and Waksman in the 1940s. Techniques and instrumentation were then developed for the safe and routine surgery of specific thoracic organs. PMID- 1907389 TI - Influence of anatomy and physiology on the management of oesophageal atresia. AB - Anatomical and physiological considerations specific to newborn infants with congenital thoracic abnormalities directly affect the timing and nature of surgical intervention during the neonatal period. This paper uses oesophageal atresia as an example of a common neonatal thoracic condition to highlight the way in which these considerations have influenced the approach to their surgical management. The type of surgical approach employed during thoracotomy determines the likelihood of subsequent chest wall deformity: an intercostal approach is preferable to rib resection. Multiple thoracotomies adversely affect the chest wall appearance and lung function. In premature infants with respiratory distress syndrome early surgical closure of the tracheo-oesophageal fistula is advantageous, and gastrostomy alone often prolongs the ventilatory difficulties. The upper oesophagus can be extensively mobilized with little danger to its blood supply, whereas the lower oesophagus, because it receives a segmental supply, is more vulnerable to ischaemia. The severity and distribution of tracheomalacia is reflected in its symptomatology. Tracheomalacia often coexists with gastro oesophageal reflux, which should be corrected by a fundoplication if respiratory symptoms persist or an oesophageal stricture develops. The numerous factors producing heat loss in the newborn during thoracotomy are discussed. It is clear that an understanding of the anatomy and physiological changes which occur in the neonate is required if these infants are to be treated effectively and safely. PMID- 1907390 TI - Cervical, cervicomediastinal and intrathoracic lymphangioma. AB - Lymphangiomas result from abnormal development of the lymphatic system, with obstruction to lymph drainage from the affected area. The neck is the most common site (25%). In this study, we review the literature of lymphangioma in the neck and thorax and have undertaken detailed analysis of 52 children with cervical lymphangioma treated during the 20 years 1969-1988. Cervicomediastinal lymphangioma is uncommon (4%) and lesions confined to the thorax are rare, with none in our series. Neck lymphangiomas occur in early childhood with half being diagnosed at birth and almost 90% before school age. All have a mass. Two-thirds are asymptomatic; sudden enlargement, inflammation, infection, feeding difficulties and respiratory symptoms occur in the remainder. Pharyngeal and laryngeal involvement, usually associated with large infiltrating lesions, results in acute airways obstruction. The respiratory symptoms caused by mediastinal extensions are usually less dramatic. Lymphangiomas have a characteristic appearance on ultrasound examination and CT scan. These investigations are mandatory for an undiagnosed intrathoracic mass and when there is clinical suspicion of mediastinal extension of cervical lymphangioma but should be obtained for neck swellings only when the clinical diagnosis is in doubt. The recommended treatment is surgical excision which can be achieved with no mortality and little morbidity. An initial period of observation is justified for asymptomatic cervical lesions because there is a small incidence (6%) of spontaneous regression. Cervicomediastinal lymphangiomas can be removed at one operation using a neck incision combined with median sternotomy. The surgeon must preserve vital structures (especially vagus, recurrent laryngeal and phrenic nerves) and should not necessarily attempt total removal of all lymphangiomatous tissue. Massive infiltrating cervical lesions pose a particular challenge and may require multiple operations over many years before a satisfactory result with good-quality survival is attained. PMID- 1907391 TI - Intralobar pulmonary sequestration. AB - Intralobar pulmonary sequestration is a rare congenital anomaly, comprising a mass of non-functioning lung tissue, without normal bronchial and vascular connections. The condition has two distinct clinical presentations: 1. In the 1st year of life, it may present as the site of a significant arterio-venous shunt, and then is usually associated with other cardiac anomalies, becoming defined in the course of appropriate cardiovascular investigations. 2. In older children, the condition becomes manifest because of persistent radiological changes and inadequate response to treatment, following one or more bouts of respiratory infection. Occlusion of the shunt or removal of the sequestration is the definitive management; the importance of the condition relates to the need to consider the diagnosis in evaluating the clinical presentations indicated above. PMID- 1907392 TI - Mediastinal masses in childhood: a review from a paediatric pathologist's point of view. AB - From 1970 to 1989, 121 children with mediastinal masses of various sorts were seen in the Department of Pathology, Royal Children's Hospital, Melbourne. The series is considered representative of the true incidence of these conditions in the state of Victoria, which had an average paediatric population during the time of this series of 900,000 children. The commonest cause of a mediastinal mass was NHL (36 cases). This was followed by HD (24 cases), then neuroblastoma and ganglioneuroma (16 and 9 cases respectively), duplication cysts (10 cases), teratomas (7 cases), neurofibroma (4 cases) and lymphangioma (3 cases). A great variety of rare conditions made up the remainder of the series and included mediastinal abscess, thymic cyst, pericardial cyst, accessory lobe of lung, plasma cell granuloma, fibromatosis, paravertebral Ewing's tumour, carcinoid tumour and neurofibrosarcoma. Presentation of the children with NHL was often acute with respiratory distress, while the child with HD was usually older and symptoms were more often systemic than local. The surgeon's role in diagnosis of these most frequently encountered mediastinal masses can be crucial and biopsy when indicated must be carried out with great care to produce material that is adequate for diagnosis and for the performance of cell marker studies and chromosome analysis. Neuroblastoma (NBL) and ganglioneuroma (GN) together were the third largest group. Children with neuroblastoma were usually young; 15 of the 18 cases were less than 2 years old. One-third of the infants with neuroblastoma presented with paraplegia and one-third with respiratory symptoms including wheeze, stridor and respiratory difficulty. Three children had Horner's syndrome. Prognosis of children with thoracic neuroblastoma is very good and contrasts with the poor outlook for those with abdominal neuroblastoma. Stage at presentation is probably the most important single prognostic variable. Ganglioneuroma presents at a later age than neuroblastoma and symptoms may be present for a long time or may be completely absent. Catecholamines, usually raised in neuroblastoma, are mostly normal in ganglioneuroma. Duplication cysts were the next most frequent group. Symptoms can often be acute and life threatening, although in three of our ten cases the cyst was an incidental finding on chest X-ray. However, only three of our patients had a normal respiratory examination. Teratomas were usually large and more often benign than malignant. Excision is the mandatory treatment and is usually curative. Although teratomas in young infants are often cellular and composed of many immature tissue types, their behaviour is benign.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1907393 TI - Extract and compounds obtained from Mandevilla velutina inhibit arachidonic acid induced ear oedema in mice, but not rat stomach contraction. AB - This study was designed to analyse the effect of crude extract (CE) and some pure compounds isolated from M. velutina on arachidonic acid (AA)-induced ear oedema in mice. The effect of these compounds on contractions in the rat stomach induced by AA and prostaglandin E2 (PGE2) was also investigated. The CE given orally to mice (50-400 mg/kg) 1h before inhibited the ear oedema in a dose-dependent manner, with a maximal inhibition (MI) of 56%. Given topically, compound MV8612 (200-600 mg/ear) isolated from this plant inhibited the oedema in a concentration dependent manner with a MI of 66%, while compounds MV8608 and MV8610 (100-600 mg/ear) caused less inhibition, MI 29% and 39% respectively. Compound MV8612, given i.p. (3-30 mg/kg) 30 min before, also caused a dose-dependent inhibition of AA-induced ear oedema (MI of 60.5% compared with 28% and 49% for MV8608 and MV8610). Indomethacin (0.25-1.0 mg/ear) applied topically had no effect, but orally (1-10 mg/kg) gave MI of 66%. Phenidone given orally (10-100 mg/kg) gave a MI of 30% but it was very potent topically (0.5-2 mg/ear) (MI 66%). Nordihydroguaiaretic acid applied either topically (0.5-2.0 mg/ear) or orally (10 100 mg/kg) caused MI of 63% and 47%, respectively. BW 755C, orally (10-100 mg/kg), inhibited the AA-induced oedema in a dose-dependent manner (MI 48%), but was less effective when applied topically (0.25-1 mg/ear) (MI 32%). In the rat stomach preparation, compounds MV8608 and MV8612 (0.1-20 micrograms/ml) had no significant effect on contractions to AA or PGE2, while indomethacin (0.01-3 micrograms/ml) potently inhibited AA contraction, but had no effect on the PGE2 response. These results indicate that MV8608 and MV8612 exhibit both a topical and a systemic anti-inflammatory profile, presumably by a mechanism not related to inhibition of cyclooxygenase. PMID- 1907394 TI - Nutrients and immune responses. AB - A wide spectrum of nutritional deficiencies, ranging from trace elements to protein, can impair normal immunologic functions. Repletion of deficient nutrients generally will restore the immune response. Under some experimental conditions, single nutrient supplementation boosts immunity; however, some mega dose therapies have been shown to suppress the immune response. Adequate nutrition is essential for maintaining the integrity of the immune system. PMID- 1907395 TI - Nutritional aspects of juvenile rheumatoid arthritis. AB - This article focuses on the factors contributing to increased risk for malnutrition in juvenile rheumatoid arthritis patients, the methods of identifying and treating nutritional problems (including protein-energy malnutrition and obesity), and outlines national statistics demonstrating that the pediatric rheumatic patient population is nutritionally underserved. The dietitian, in conjunction with the interdisciplinary treatment team, should be involved in the initial evaluation of all juvenile rheumatoid arthritis patients to facilitate early detection of nutritional problems and initiate nutritional intervention strategies. PMID- 1907396 TI - Endoscopic visualization of aspergilloma. PMID- 1907397 TI - [Nutritional support of the patient with AIDS]. PMID- 1907398 TI - [Nutrition of the burn patient]. PMID- 1907399 TI - Nutritional effects on response of children in developing countries to respiratory tract pathogens: implications for vaccine development. AB - Malnutrition and respiratory disease commonly occur together, and the immunologic defects caused by malnutrition may affect clinical responses and the impact of vaccines. These defects include impaired maturation and function of T lymphocytes, diminished secretory immune responses, poor humoral antibody responses to polysaccharide antigens, deficient complement activity (especially the alternative pathway), and impaired antimicrobial mechanisms by phagocytic cells. In addition, protein-energy malnutrition often leads to very high serum levels of IgE as a result of altered T cell regulation of IgE production and may contribute to IgE-mediated pathologic responses to respiratory syncytial virus or parainfluenza virus infection. Correction of these deficits may improve host response to infection and enhance vaccine-related protection. Both vitamin A and iron deficiency states have been epidemiologically associated with increased morbidity due to respiratory infection. The impact of preventive therapy with either vitamin A or iron is still uncertain, but such therapy has the potential for diminishing the incidence of respiratory infections and their consequences. PMID- 1907400 TI - Excessive fear of PCBs. PMID- 1907401 TI - Density-dependent natural selection and trade-offs in life history traits. AB - Theories of density-dependent natural selection state that at extreme population densities evolution produces alternative life histories due to trade-offs. The trade-offs are presumed to arise because those genotypes with highest fitness at high population densities will not also have high fitness at low density and vice versa. These predictions were tested by taking samples from six populations of Drosophila melanogaster kept at low population densities (r-populations) for nearly 200 generations and placing them in crowded cultures (K-populations). After 25 generations in the crowded cultures, the derived K-populations showed growth rate and productivity that at high densities were elevated relative to the controls, but at low density were depressed. PMID- 1907402 TI - "Primary" gonococcal meningitis. AB - A 39-year-old man had meningitis, which subsequently proved to be due to Neisseria gonorrhoeae. This report describes the second known case of primary gonococcal meningitis. This disease mimics meningococcal meningitis closely, and the diagnosis can only be made by careful bacteriologic study. PMID- 1907403 TI - Urogenital infection due to meningococcus in men and women. AB - The authors report six cases of acute urethritis and three cases of acute cervicitis caused in all instances by Neisseria meningitidis group B. The patients, five heterosexual men, one homosexual man, and three female prostitutes were seen at a venereal clinic in Mexico City. All of them were initially diagnosed as having gonorrhea. Treatment with procaine-penicillin G cured all cases, both clinically and bacteriologically. These experiences reinforce the need to distinguish N. meningitidis from N. gonorrhoeae in the setting of sexually transmitted diseases. PMID- 1907404 TI - Clinical and microbiologic features of urethritis in men in Toulouse, France. AB - On hundred twenty-six men who attended a hospital microbiology laboratory and 99 men who attended a private laboratory in Toulouse, France, for symptoms of urethritis were examined during 1988, for evidence of urethral pathogens. The following incidences were found: Neisseria gonorrhoeae: 24 (10.7%); Chlamydia trachomatis: 58 (25.8%); Ureaplasma urealyticum: 46 (20.4%); Gardnerella vaginalis: 21 (9.3%); Haemophilus parainfluenzae: 21 (9.3%); Streptococcus agalactiae: 15 (6.7%); Candida albicans: 10 (4.4%); and Trichomonas vaginalis: 4 (1.8%). The prevalence of these microorganisms was similar in the two groups of patients. No pathogen was isolated from 71 patients (31.6%). Mixed infections with at least two pathogens were found in 49 men (21.8%). Another goal of this study was to determine the relative prevalence of urethral pathogens in relation to clinical findings. N. gonorrhoeae was isolated significantly more often in patients who had a urethral discharge (P less than .05) that contained five or more polymorphonuclear cells per high-power field (PMN/HPF) (P less than .001). G. vaginalis was isolated significantly more often in patients who did not have an urethral discharge (P less than .05) and in men with less than five PMN/HPF (P less than .05). Isolation of C. albicans was significantly associated with pruritus (P less than .05) and balanitis (P less than .001). Like the clinical features, the gram-stained urethral smear was of limited value in diagnosis and therapeutic decision-making regarding non-gonococcal urethritis. In contrast, this study underlines the importance of full identification of urethral isolates in the management of urethritis in men. PMID- 1907405 TI - Bacteriologic studies on Neisseria gonorrhoeae isolated in Sapporo, Japan: investigation of beta-lactamase production and auxotypes. AB - The authors studied the annual incidence of isolation of penicillinase-producing Neisseria gonorrhoeae (PPNG) strains among the total number of strains of N. gonorrhoeae (1,401 strains) that were isolated in Sapporo, Japan during 1980 1989. During the first half of the 1980s, there was a tendency for PPNG to increase, and the peak incidence was 23.9% in 1985. Thereafter, the incidence of PPNG decreased to an isolation rate of 6.3% in 1989. In addition, the auxotypes of 592 of 1,401 isolated strains of Neisseria gonorrhoeae were studied during three periods: 1980-1985, 1986-1987, and 1988-1989. Among the 592 strains, 315 strains were tested for sensitivity to the action of amoxicillin. In the 1988 1989 period, the auxotype showed an increasing incidence of the auxotype that requires arginine, hypoxanthine, and uracil (i.e., AHU), whereas the proto- and pro-types decreased in incidence. The AHU strains showed higher sensitivity to amoxicillin administration compared with the proto- and pro-strains. PMID- 1907406 TI - Central nervous system monitoring. What helps, what does not. AB - The ICU monitoring of CNS function can make a difference in the clinical outcome. No single technique addresses the multiple issues that arise in the ICU setting, especially for the polytrauma patient. Multimodality approaches combining assessment of cerebral blood flow, electrophysiologic parameters, and intracranial pressure, when appropriate, with cardiac and respiratory monitors are being developed at a number of traumatology centers world wide. Experience needs to be gained to establish the best combination of these modalities. Pending this, selected use of intracranial pressure monitoring combined with EEG and transcranial Doppler ultrasound provides reliable immediate assessment and ongoing monitoring of CNS structures. PMID- 1907407 TI - Nutritional support in the critically ill surgical patient. AB - Aggressive nutritional support in the critically ill surgical patient is essential if improved outcome is to be realized. An understanding of the metabolic alterations of trauma and sepsis provides the foundation for a nutritional prescription for the individual patient. Careful nutritional assessment; titration of fluid, electrolytes, and micronutrients; provision of adequate calories and nitrogen to meet metabolic needs; and the selective use of specialized formulations are important components of nutritional management in the ICU. PMID- 1907408 TI - Quality assurance in the surgical intensive care unit. Where it came from and where it's going. AB - The early history of QA is one of stunning achievements. Men and women led by a vision of what hospital health care should be brought about fundamental changes in the structure of hospitals and medical schools. These successes required lifetimes of work and enormous capital (Flexner's war chest would have amounted to billions of 1990 dollars). A second wave of reform included the creation of credentialing committees, tissue committees, and infection control efforts. Although less dramatic in their impact, these efforts have had measurable influence on the outcome of health care and, under the joint administration of local hospitals and the JCAHO, continue to guarantee excellence in health care. The most recent attempts at quality assurance, driven at least in part by a federal mandate to control costs, have been much more modest in their success. Committed groups working within a sound theoretical framework have had great difficulty monitoring and evaluating centrally a process as decentralized as health care. The regularity with which new fashions in QA have appeared underscores the frustration felt with this approach. If the quality of health care is to be monitored centrally, reliable measures of quality will be required. No one knows if such measures actually exist. The absence of objective evidence that quality has been improved by these efforts suggests that little has been accomplished, perhaps because all easily attainable improvements had already been implemented. The basic concept of a centrally monitored hospital structure within which provision is made for ongoing observation and innovation by those actually involved in the care of patients retains the advantages of central monitoring and local invention. It is a model that will be hard to improve on. We should persist in our efforts, but fundamental advances are unlikely. In the end, quality is only doing everything the best it can be done. The best quality assurance requires an excellent hospital in which a well-trained and committed staff has a central mandate and local purview to do the best possible job. Two thousand years after Hammurabi's minions busied themselves determining the appropriate punishment for various medical misadventures, the Greek Hippocrates advocated a less complex approach to the same problem. He suggested that the quality of health care could be best guaranteed by administering an oath to physicians, exhorting them simply to do what was best for their fellow men. This approach has seen us through two millennia and, however variable its results, may not be easily improved on. PMID- 1907409 TI - Identity of a biliary metabolite formed from monocrotaline in isolated, perfused rat liver. AB - A pneumotoxic pyrrolic metabolite, previously isolated from the bile when rat liver was perfused with the pyrrolizidine alkaloid, monocrotaline, has been identified as 7-glutathionyl-dehydroretronecine. The metabolite showed a TLC spot and HPLC peak corresponding with the latter compound, and a procedure for replacing the thioether group with an ethoxy group converted the metabolite to dehydroretronecine 7-ethyl ether, confirming that the glutathionyl moiety was attached to the 7-position of dehydroretronecine. The same metabolite was detected in bile from rat liver perfused with retrorsine, which is a diester alkaloid similar to monocrotaline, whereas it was not formed from heliotrine, an alkaloid lacking the 7-ester function. PMID- 1907410 TI - Enhancement of cell-mediated cytotoxicity by Clostridium difficile toxin A: an in vitro study. AB - Cells from the immune system exhibiting cytotoxic activity are able to kill tumor or infected cells in a major histocompatibility complex-restricted (cytotoxic lymphocytes) or non-restricted (natural killer cells) manner. In order to exert such a cytotoxicity they have to bind the target cell and release cytotoxic factors able to induce target cell death. Treatment of human peripheral blood mononuclear cells with toxin A from Clostridium difficile induced an enhancement of the cytotoxic efficiency of these effector cells. Morphological analysis of effector/target cell pairs seems to suggest that this could be related to an increased ability of cytotoxic effectors to establish close and intertwined contacts with target cells. These contacts involve adhesion molecules and lead to the formation of a "closed chamber" which probably improves the efficacy of lytic factors and results in an increased cytotoxicity. PMID- 1907411 TI - Lipoxygenase-mediated secretory effect of canatoxin the toxic protein from Canavalia ensiformis seeds. AB - Canatoxin was shown to induce serotonin release from rabbit platelets and rat brain synaptosomes, as well as to release insulin from isolated pancreatic islets. All these effects were dose-dependent and were inhibited by lipoxygenase inhibitors, such as nordihydroguaiaretic acid and esculetin, but not by indomethacin, a cyclooxygenase inhibitor. The data suggest that canatoxin-induced secretory effect results from the activation of the lipoxygenase pathway which would elicit exocytosis. Thus, canatoxin might be a useful tool for the study of biological events that involve lipoxygenase mediation. PMID- 1907413 TI - [Total hip alloplasty. The long-term economical consequences]. AB - A cost-effectiveness analysis concerning total hip arthroplasty was undertaken in 1984. The analysis included 86 patients submitted to operation in Odense and Svendborg Hospitals. After a follow-up period of five years, revision had proved necessary in one patient but no re-operations were undertaken on account of deep infection or aseptic loosening of the implants. The annual accumulated netto cost of total hip arthroplasty including the costs of readmission was calculated to be approximately 23,000 Danish crowns (2,000 pounds). This must be compared with a lasting marked improvement in the quality of life resulting from operation. PMID- 1907412 TI - Isolation of two toxic heptapeptide microcystins from an axenic strain of Microcystis aeruginosa, K-139. AB - Two toxic heptapeptides were isolated from an axenic Microcystis aeruginosa strain, K-139. Using mainly a non-destructive NMR method, we determined the structure of the major toxin to be 7-desmethylmicrocystin LR which lacks an N methyl group of the dehydroalanine moiety of microcystin LR. The minor toxin was deduced to be 3,7-didesmethylmicrocystin LR. The chromatographic and NMR analyses of 7-desmethylmicrocystin LR were compared with those of 3-desmethylmicrocystin LR. PMID- 1907414 TI - Large-scale preparation of a highly purified solvent-detergent treated factor VIII concentrate. AB - Large-scale adaptation of a recently reported glycine precipitation method for the production of factor VIII (FVIII) concentrate is described. Scaling up of the method required some modification including the addition of aluminum hydroxide to the glycine buffer to reduce the level of contaminating proteins in the final preparation and the use of centrifugation to replace filtration by glass beads. Furthermore, the resultant product was virus inactivated by incorporation of the organic solvent and detergent technique. At industrial level, the modified method gave a good recovery of FVIII activity (230 IU/l plasma) with high purity (4 IU/mg protein). The final product, after virus inactivation and lyophilization, yielded 185 IU of FVIII activity per liter of starting plasma and was considered to be suitable for clinical evaluation. PMID- 1907416 TI - Successful treatment of severe Rh iso-immunization with immunosuppression and plasmapheresis. AB - Nine patients with severe Rh iso-immunization were treated by plasma exchange combined with immunosuppression. Apart from 3 abortions, previous pregnancy losses consisted of 7 intra-uterine and 5 neonatal deaths. Only 2 patients had had no previous pregnancy loss. Differences in the optical density of the amniotic fluid of 8 patients fell into the upper Liley zone. There was one intra uterine death due to abruptio placentae but no neonatal deaths. When the outcome of the pregnancy immediately preceding the treatment pregnancy was compared to the treatment pregnancy, the fetal loss was reduced from 6 to 1. No adverse fetal effects were encountered. PMID- 1907415 TI - Hepatitis C virus antibodies in high-risk Saudi groups. AB - The recombinant-based enzyme immunoassay developed by Ortho Diagnostic System for the detection of antibodies of hepatis C virus (HCV) was used to determine the extent of exposure to HCV in healthy Saudi subjects (500 males; 260 females) without liver disease and with no history of percutaneous exposure to blood and in Saudis who are considered at high risk for contracting the disease: hemophiliacs (28), thalassemics (78), hemodialysis patients with renal failure (65) and patients with sexually transmitted diseases (STD) (220). The results show that HCV is endemic in the Saudi population with an overall frequency of 5.3% in healthy Saudi adults which is at least 5 times higher than what has been reported from Western Europe and the United States. Seropositivity rate in the high-risk groups ranges from 15.9% in patients with STD to 78.6% in hemophiliacs. These data underscore the urgent need for routine anti-HCV screening of blood donations in order to reduce the frequency of postransfusion non-A, non-B hepatitis and its sequelae in the Saudi population. PMID- 1907417 TI - Seminoma: a review of 15 years experience. AB - We retrospectively reviewed the Charleston Area Medical Center (CAMC) experience with 54 patients diagnosed with seminoma between 1970 and 1986. The median age at diagnosis was 37.5 years (range 20-79). The highest percentage of seminomas occurred between the ages of 30 and 39 (50 percent). Treatment was primarily orchiectomy and radiotherapy since most patients presented with localized disease. The five year survival rate was 100 percent for stage I, 86 percent for stage II, and 75 percent for stage III. Sixteen of 18 (89 percent) stage I patients survived at least 10 years. Of the 12 patients who died, two (16 percent) died of recurrent seminoma, six of cardiovascular disease, and four of a second primary malignancy. The excellent five and 10-year survival rates in stage I seminoma treated with surgery and radiotherapy in this series is similar to others. PMID- 1907418 TI - [Identification of twenty-eight species mycobacteria with their cellular fatty acids by capillary gas chromatography]. AB - Cellular fatty acid (FA) of 28 species of mycobacteria were analysed by capillary gas chromatography (GC). There were more than sixty volatile FA before C12:0 have no any difference between species both in quality and quantity. The identification scheme of Mycobacterium based on cellular FA was presented here. According to this scheme, all the tested species could be divided into 8 groups by the FA peak height order of C18:1, C18:0 and TBSA which were quite stable; after that, 17 species (60%) might be identified to species level with help of some distinctive FA such as C19:0, C21:0. Most pathogenic bacteria could be separated by the scheme (M. tuberculosis, M. bovis and some complexes). This scheme was also demonstrated to be objective rationality by computer cluster analysis with cellular FA components. PMID- 1907420 TI - Effects of rice bran fibre and cholestyramine on the faecal excretion of Kanechlor 600 (PCB) in rats. AB - 1. As rice bran fibre binds Kanechlor 600 (PCB), the present study was conducted to determine whether the fibre stimulates rat faecal excretion of PCB in vivo. 2. In rats fed diets containing rice bran fibre, lignin and cholestyramine, the faecal excretion of PCB was increased. Total PCB excreted in rat faeces for groups fed diets of 10% (w/w) rice bran fibre, 10% fibre plus 5% lignin, 5% cholestyramine and 10% fibre plus 5% cholestyramine were 3.4, 3.7, 2.2 and 5.4 times as much, respectively, as that of control rats. The greatest effect on the faecal excretion of PCB was thus obtained with rice bran fibre plus cholestyramine. 3. In rats fed these diets, PCB concentration of the small intestine was significantly decreased to 25-50% of that of controls. PCB of spleen in rats fed diets of 10% fibre, 10% fibre plus 5% lignin and 10% fibre plus 5% cholestyramine also decreased to 50% of that of controls. However, PCB of other tissues were not affected. PMID- 1907419 TI - Metabolism of pravastatin sodium in isolated rat hepatocytes. II. Structure elucidation of the metabolites by n.m.r. spectroscopy. AB - 1. The structures, including stereochemistry, of the two major metabolites of pravastatin sodium in an isolated rat hepatocyte system, i.e. the 4'a alpha glutathione conjugate (CM-1) and the 3',5'-dihydrodiol (CM-2), were determined by one- and two-dimensional n.m.r. spectroscopy. 2. The structures of two synthetic pravastatin epoxides, possible precursors of the metabolites, were also established. 3. One of the synthetic epoxides, 4'a beta, 5' beta-epoxide was converted to the pravastatin metabolite, 4'a alpha-glutathione conjugate (CM-1) by a rat liver cytosol system and is proposed as the common metabolic intermediate between pravastatin sodium and the metabolites, CM-1 and CM-2. PMID- 1907421 TI - Biosynthesis and characterization of glucuronide metabolites of fluphenazine: 7 hydroxyfluphenazine glucuronide and fluphenazine glucuronide. AB - 1. To expedite direct studies on phase II metabolites of fluphenazine, pure fluphenazine or 7-hydroxyfluphenazine were incubated with a rabbit hepatic microsomal immobilized enzyme system. After purification and recrystallization a high yield (60%) of 7-hydroxy-beta-D-O-glucuronyl-fluphenazine was obtained. 2. The structure of this glucuronide was proven unambiguously by mass spectrometry (fast atom bombardment, daughter ion analysis, electron impact, chemical ionization) and 1H-n.m.r. and 13C-n.m.r. spectroscopy. The phenolic ether glucuronide was the sole product of the reaction. 3. There was no evidence of conjugation at the primary alcohol group of the side-chain of fluphenazine, or of the formation of quaternary ammonium-linked glucuronides with either of tertiary aliphatic nitrogen atoms of the side-chain. 4. Incubation of fluphenazine with the immobilized enzyme system gave a poor yield (less than 1%) of the aliphatic ether glucuronide as reaction product, consistent with a low susceptibility of the side-chain primary alcohol function of fluphenazine to glucuronidation. PMID- 1907423 TI - [Evaluating thyroid gland function in patients with protein anomalies]. AB - The euthyroid hyperthyroxinemia (EHT) is characterized on the one hand by a normal basal THS or TRH-TSH response but also by high plasma values of total thyroxine (TT4) on the other. However if only TT4 is assessed, "hyperthyroidism" may be diagnosed erroneously. EHT may be caused by an increase of specific thyroxine binding proteins which may be hereditary (permanent) or acquired (transient). The most frequent disturbance is due to an estrogen induced increase of thyroxine binding globulin (TBG) in the course of pregnancy, anticonceptive drugs or estrogen treatment. The albumin associated HT (FDH syndrome), first reported in 1979, has autosomal dominant traits. 144 patients with FDH syndrome were observed during the period between 1984 and 1990, i.e. 7% (1986) of all hyperthyroid patients explored. Family screening is required to prevent unjustified treatment. Additionally existing disturbances of thyroid function as well as other protein binding anomalies may both cause problems in differential diagnosis. Prealbumin associated hyperthyroxinemia (PAAH), first published in 1982, may be due to an inherited increase in affinity, but may also be the consequence of a true elevation of prealbumin plasma concentration in the course of an islet cell cancer; both conditions are extremely rare. Nearly as rare are patients with plasma autoantibodies directed against T4 and/or T3 (5 cases); yet, a reverse T3 autoantibody could be observed in merely 1 case. By means of our modified radio-thyroxine-agarosegel-iceelectrophoresis all such protein anomalies may be diagnosed and differentiated in 1 procedure. Moreover, all other types of EHT must be taken into consideration by differential diagnosis. PMID- 1907422 TI - [Dose and time dependence of hemodynamic tolerance development during intravenous nitrate therapy in acute myocardial infarct]. AB - Intravenous nitroglycerin therapy during acute myocardial infarction has beneficial effects on infarct size, infarct complications, and mortality. Numerous dosage formulas for the continuous administration of nitrates are currently used, although several studies have demonstrated the rapid development of tolerance during long-term treatment in patients with ischemic heart disease. The dose and dosage of a continuous nitrate application in the clinical setting of acute myocardial infarction has thus yet to be resolved. This study investigated the hemodynamic effects of a 60-h, low- (33 micrograms/min) vs high- (133 micrograms/min) dose intravenous nitroglycerin (NTG) infusion in 16 patients with uncomplicated acute myocardial infarction. In group I (33 micrograms/min NTG; n = 8) the initial nitrate effect on the pulmonary capillary pressure (PCP control: 14 +/- 1.5; 4 h: 7 +/- 0.9; 60 h: 7 +/- 0.8; mean +/- SEM; all values in mm Hg) and mean pulmonary artery pressure (PAPM-control: 23 +/- 2.3; 4 h: 15 +/- 1.3; 60 h: 14 +/- 1.3) remained unchanged for 60 h. In group II (133 micrograms/min NTG; n = 8) an almost complete loss of the initial effect on PCP (control: 15 +/- 1.6; 4 h: 5 +/- 1.4; 60 h: 12 +/- 1.3) and PAPM (control: 25 +/- 2.0; 4 h: 14 +/- 1.8; 60 h: 20 +/- 1.3) was observed. In contrast to high-dose application the low-dose NTG-infusion induced comparable acute hemodynamic effects that were not attenuated by tolerance development. PMID- 1907424 TI - [Cerebral cortex and psychiatry]. PMID- 1907425 TI - Mouse kidney histamine N-methyltransferase: assay conditions, biochemical properties and strain variation. AB - Histamine N-methyltransferase (HNMT) catalyzes the N tau-methylation of histamine and structurally-related compounds. Levels of HNMT activity in the human red blood cell are regulated by inheritance. The inbred mouse is an ideal laboratory animal in which to study the genetics of inherited traits. Therefore, HNMT activity was measured in renal homogenates of A/J mice to establish optimal assay conditions and to determine the properties of mouse kidney HNMT as a first step toward testing the hypothesis that large strain-related variations in HNMT activity might exist among inbred strains of mice. Apparent Km values for histamine and S-adenosyl-L-methionine, the two cosubstrates for the reaction, were 26 and 1.7 microM, respectively. IC50 values for the inhibition of mouse kidney HNMT by amodiaquine and S-adenosyl-L-homocysteine were 1.67 and 11.8 microM, respectively. HNMT activity levels were then measured under optimal assay conditions in renal preparations from male animals of eleven inbred mouse strains chosen because of the availability of recombinant inbred (RI) animals derived from the parental strains. Average values for renal HNMT activity varied among strains by less than two-fold and ranged only from 26.2 +/- 0.51 (mean +/- SEM) units/mg protein in AKR/J mice to 39.1 +/- 2.58 units/mg protein in C57BL/6J animals. Renal HNMT activities in females of the three strains in which both sexes were studied were 11-13% higher than were those in renal tissue from males of the same strain. In summary, the properties of HNMT in the mouse kidney are similar to those of HNMT in other species, but strain variation in levels of enzyme activity among the 11 inbred mouse strains studied was insufficient for these animals to be used in biochemical genetic experiments. PMID- 1907426 TI - Inhibitory effects of gamma-interferon on bradykinin-induced bone resorption and prostaglandin formation in cultured mouse calvarial bones. AB - The effects of mouse recombinant gamma-interferon (gamma-IFN) and indomethacin on bone resorption stimulated by bradykinin, Lys-bradykinin, Met-Lys-bradykinin, des Arg9-bradykinin and prostaglandin E2 (PGE2) have been studied using cultures of neonatal calvarial bones and analyzing the release of 45Ca from prelabelled bones as a parameter of bone resorption. In addition, the effects of gamma-IFN and indomethacin on formation of PGE2 in bone cultures stimulated by bradykinin was analyzed. Indomethacin (1 mumol/l) totally abolished bradykinin (1 mumol/l) induced 45Ca release. The inhibitory effect of indomethacin could be fully reversed by addition of PGE2 (1 mumol/l). gamma-IFN (1000 U/ml) almost totally inhibited 45Ca release stimulated by bradykinin (1 mumol/l), but the inhibitory effect could only be partially overcome by PGE2. gamma-IFN and indomethacin also inhibited the stimulatory effects of Lys-bradykinin, Met-Lys-bradykinin and des Arg9-bradykinin (1 mumol/l) on 45Ca release. The stimulatory effects of PGE2 (1 mumol/l) on radioactive calcium mobilization was partially inhibited by gamma-IFN (1000 U/ml), whereas indomethacin (1 mumol/l) was without effect. The inhibitory effect of gamma-IFN on 45Ca release stimulated by bradykinin and PGE2 was dose dependent with threshold for action at 3-30 U/ml. Comparative dose-response curves showed that gamma-IFN was most potent as inhibitor of bradykinin induced 45Ca release. Bradykinin (1 mumol/l) significantly stimulated PGE2 formation by a mechanism that was completely inhibited by indomethacin (1 mumol/l). gamma-IFN (1000 U/ml) partially inhibited the stimulatory effect of bradykinin on PGE2 formation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1907427 TI - Plasma histamine and clinical tolerance to infused histamine in normal, atopic and urticarial subjects. AB - Five subjects with a recent history of urticaria (U), five atopic (A) subjects and a non-atopic (NA) control group were given intravenous infusions of histamine starting at 0.05 micrograms/kg/min, increasing by 0.05 micrograms/kg/min every 30 minutes to a maximum of 0.35 micrograms/kg/min. Plasma histamine levels were monitored every 15 minutes. The infusion was stopped when an objective clinical endpoint was reached, involving either evidence of peripheral vasodilatation (rise of skin temperature by at least 1 degree C) or a 20% fall of peak expiratory flow rate. There were no significant differences in resting plasma histamine in the three groups. Those with urticaria reached the clinical endpoint at a lower infusion rate than non-atopic subjects (U 0.22 +/- 0.02 micrograms/kg/min; A 0.26 +/- 0.02 micrograms/kg/min; NA 0.32 +/- 0.2 micrograms/kg/min. p less than 0.008) they also received a lower total histamine dose (U 1.12 +/- 0.33 mg; A 1.42 +/- 0.38 mg, NA 2.2 +/- 0.51 mg, p less than 0.008). Atopic subjects with a history of asthma, eczema or rhinitis also tolerated histamine poorly, some subjects reaching a clinical endpoint while the plasma histamine level was still relatively low (U 1.52 +/- 0.4 ng/ml, A 0.85 +/- 0.19 ng/ml, NA 1.4 +/- 0.44 ng/ml, p = 0.05). After the histamine infusion was stopped, the fall in the blood level of histamine was slower in urticarial subjects than in the other two groups, with a half-life of 6.2 +/- 1.3 min (A 3.0 +/- 1.2 min, NA 4.0 +/- 0.7 min, p less than 0.02). There were thus differences in the metabolism of histamine in our non-atopic urticarial subjects and increased histamine sensitivity in atopic subjects which require further study. PMID- 1907428 TI - Adjuvant therapy of stage II breast cancer treated with CMFVP, radiation therapy and VATH following lumpectomy. A pilot trial. AB - A pilot study was undertaken to assess the feasibility, toxicity, and efficacy of combined radiation therapy and chemotherapy in the adjuvant treatment of node positive. Stage II patients with breast carcinoma who had undergone lumpectomy. Therapy consisted of three phases, starting with a six-week CMFVP (cyclophosphamide, methotrexate, 5-fluorouracil, vincristine, prednisone) induction, followed by radiation therapy to the breast, and concluding with four cycles of VATH (vinblastine, Adriamycin, thiotepa, Halotesin). Twenty-seven patients were entered with an average age of 51.5 years (median 50 yrs) and a mean follow-up of 46.2 months. Twenty-three patients (85.2%) are alive and 19 (70.3%) disease free. There were no ipsilateral local recurrences. Cosmetic results were good to excellent in 26/27 patients. The doses of VATH were not compromised by the prior therapy. The regimen was found to be tolerable and is a reasonable approach in the adjuvant treatment of this particular patient population. PMID- 1907429 TI - Red blood cell alloimmunization complicating plasma transfusion. AB - Well-known adverse effects of plasma transfusion include viral transmission, allergic complications, and rare anaphylactic reactions. In making clinical decisions to transfuse plasma, a seldom-considered complication is that of red blood cell (RBC) alloimmunization. The authors report a patient in whom strong IgM and IgG anti-E and weak IgG anti-JKa RBC antibodies developed 15 days after infusion of two units of fresh-frozen plasma for volume expansion. These antibodies are potentially hemolytic. This case underscores the importance of considering risks of plasma infusion. Plasma should not be used casually, especially for indications for which alternate therapies, such as crystalloid and colloid solutions, are available. PMID- 1907430 TI - Hospital-based skilled nursing facilities to the rescue. PMID- 1907431 TI - Treatment of compound fractures. AB - Management of compound fractures remains a challenge to the surgeon. Methods to decrease patient morbidity include early fracture stabilization and sequential debridement. External fixation remains the standard; however, early internal fixation in low-grade injuries may be an acceptable option. Early soft tissue coverage is critical. The use of prophylactic parenteral antibiotics has decreased the incidence of acute infection and chronic osteomyelitis. Supplemental use of local antibiotic polymethyl methacrylate (PMMA) beads appears to further diminish the morbidity in high-grade open fractures. PMID- 1907433 TI - [The potentials of combined chemotherapy in disseminated ovarian cancer]. PMID- 1907434 TI - Capnography and sticking valves in the circle system. PMID- 1907432 TI - Arteriographic findings in EDTA chelation therapy on peripheral arteriosclerosis. AB - In a randomized, double-blind, controlled study, 153 patients with claudication were each given either 20 infusions of Na2EDTA or 20 infusions of saline. Walking distances and ankle/brachial indices were measured before, during, and after treatment. In 30 patients, angiograms and transcutaneous oxygen tensions were obtained before, during, and after treatment. The patients' subjective evaluations of the effect of treatment were also recorded. It is concluded that EDTA chelation therapy has no effect in patients with intermittent claudication in the legs caused by arteriosclerosis. PMID- 1907435 TI - Diagnostic methods for the determination of iduronic acid in oligosaccharides. AB - A high-performance liquid chromatography (HPLC) method with pulsed amperometric detection (PAD) was used for the determination of the acid hydrolysis products of L-iduronic acid containing oligosaccharides isolated from biological sources. This HPLC-PAD method was compared with gas chromatographic (GLC) methods. Since acid hydrolysis of oligosaccharides can produce a number of products, several uronic acid derivatives were prepared by chemical synthesis. These well characterized standards in conjunction with mass spectrometry allowed for the identification of most of the products of methanolysis or hydrolysis of glycosamino-glycans, which included chondroitin sulfates A and B (dermatan sulfate), heparin, and hyaluronic acid. (4 M) HCl in methanol 100 degrees C for 24 h was found to be optimum for GLC and 1 M aqueous HCl for 4 h at 100 degrees C for HPLC-PAD. All of the monosaccharides, hexosamines, and uronic acids could be separately identified in a single chromatographic step using either technique. Good resolution, high sensitivity (low microgram samples) and rapid analysis makes these methods particularly useful for the determination of small amounts of glycosaminoglycans and other glycoconjugates found in samples isolated from biological sources. These two techniques are specifically designed to allow the qualitative determination of the carbohydrate content and composition of samples whose carbohydrate composition and content is completely unknown. PMID- 1907436 TI - Use of nitrocellulose membrane to activate and measure insect prophenol oxidase. AB - A method for the activation and measurement of insect prophenol oxidase using nitrocellulose membrane is presented. Using this method we were able to conveniently activate both crude and purified prophenol oxidase from insects belonging to three different orders. This rapid method allows for prophenol oxidase activation, in the absence of a prophenol oxidase-activating system, and in the presence of high ionic strength, protease inhibitors, or chelator. PMID- 1907437 TI - Simultaneous measurement of metabolic heat rate, CO2 production, and O2 consumption by microcalorimetry. AB - This study describes methods and equipment for measurement of metabolic heat rates of cells and tissues under conditions that provide simultaneous determinations of the flux rates of both O2 and CO2. Isothermal measurement of metabolic heats are conducted in a sealed ampule. A trapping solution is employed to absorb metabolic CO2. Absorption of CO2 produces heat at a rate proportional to the rate of CO2 production. Under these conditions, O2 consumption by the tissue results in a decrease in the partial pressure of O2 within the sealed ampule. The decrease in pressure can be monitored with a pressure sensor and related to O2 consumption rates. The combined measurements of heat rates, CO2, and O2 fluxes provide important information on bioenergetic efficiency of cell metabolism. These data can also suggest possible shifts in metabolic pathways or substrate sources as cells develop, or are exposed to effectors, inhibitors, and environmental factors. PMID- 1907438 TI - Prevalence of nosocomial infection in long-term-care Veterans Administration medical centers. AB - Prevention and control of nosocomial infections are major goals of institutional risk-management programs. However, variations in criteria and denominator parameters make comparison of rates across settings difficult. This study addressed those problems by reporting criteria used to identify infections and applying the same denominator across long-term-care facilities. Findings demonstrated a 9.8% prevalence rate for nosocomial infections in four long-term care VA facilities. Most of the identified infections were consistent with Centers for Disease Control definitions of nosocomial infections. The most frequent indicators of nosocomial infections that did not fully meet those definitions were (1) documented symptoms, (2) antibiotic therapy, and (3) physician diagnosis. PMID- 1907439 TI - Indigenous multiresistant bacteria from flowers in hospital and nonhospital environments. AB - The microbial flora of 60 vase water samples from cut flowers obtained from several environments, including a hospital, were examined in this study. Forty one different bacterial species were identified, including 12 species of Pseudomonas. The mean total aerobic bacterial count per 500 ml of vase water was 4.5 x 10(8) organisms, and high levels of antibiotic resistance were found. To ascertain the origin of the bacteria found on the flowers as well as their growth patterns, natural cut flowers were compared with sterilized cut flowers in tap water over time. Although the density of organisms was similar, the flora in vase water of sterilized flowers consisted almost entirely of aerobic spore formers while mixed flora of gram-negative bacteria, staphylococci, aerobic spore formers, and fungi were isolated from natural flowers. Our results indicate that the multiply-resistant microbial flora found in vase water is indigenous to flowers, rather than originating from the environment in which they are placed, and that such water is a reservoir of large numbers of multiresistant organisms. PMID- 1907440 TI - Tissue plasminogen activator release and plasminogen activator inhibitor levels in coronary artery disease. AB - Unstable angina and Q wave myocardial infarction are associated with intraluminal coronary thrombosis, a process to which impaired fibrinolysis may contribute. The authors examined the extrinsic fibrinolytic system, including tissue plasminogen activator antigen, plasminogen activator inhibitor activity and antigen, and euglobulin clot lysis time before and after venous occlusion in 56 patients undergoing coronary angiography for chest pain syndromes and in 16 healthy controls. Fibrinolysis variables were similar (with greater than 95% confidence) in the patients with thrombus-associated coronary syndromes as compared with those with chest pain syndromes not due to coronary thrombosis. These fibrinolytic variables were also similar to those in patients without coronary artery disease and in healthy controls. Their data suggest that defective fibrinolysis is not involved, at least systemically, in the pathogenesis of thrombus-associated coronary artery syndromes. PMID- 1907442 TI - Hepatitis C from a needlestick injury. PMID- 1907441 TI - Hepatitis C in hospital employees with needlestick injuries. PMID- 1907443 TI - Incidence and prevention of conjunctival contamination with blood during hazardous surgical procedures. AB - The incidence and risks of conjunctival contamination with patients' blood during a range of otolaryngological surgical procedures was assessed. Risks were found to be highest in three groups of procedures; tracheostomy, operations preceded by local anaesthetic injections and procedures involving the use of the air drill. A simple and effective method of protection using spectacles with large plain lenses is presented. PMID- 1907444 TI - Gastro-oesophageal reflux in mechanically ventilated preterm infants. AB - Long duration oesophageal pH recordings were performed on 42 mechanically ventilated and parenterally fed preterm infants for a mean (SD) of 94 (28) hours. Their mean (SD) gestational age was 31.5 (2.6) weeks and birth weight 1514 (448) g. Their mean postnatal age was 19 (10) hours at the onset of pH recording, which was performed with the babies supine. The mean hourly values for the total number of episodes of gastro-oesophageal reflux (GOR) was 2.3 (2.7), for acid GOR 1.2 (1.4), and for acid GOR longer than 5 minutes 0.08 (0.09). The time the pH was greater than 4 (the reflux index) was 3.5 (3.3)% and the mean airway pressure was 6.6 (5.1) cm H2O. Fifteen infants had a reflux index above 5%. GOR patterns were not significantly correlated to birth weight, gestational age, postconceptional age, ventilatory patterns, and duration of mechanical ventilation. We concluded that the reproducibility of the reflux index was low because the median of the absolute differences was 1% when two consecutive 12 hour periods were compared and reached 2.5% when the two periods were separated by 96 hours. A second 24 hour pH recording was performed in 30 of the 42 patients after weaning from the ventilator and at a time when patients were asymptomatic and enterally fed. Compared with the late postprandial period of the second pH recording, the first recording showed an increase in the number of episodes of GOR and a decrease in reflux index, without any difference in the number of episodes of acid GOR. PMID- 1907446 TI - A pound of prevention when there isn't a cure. PMID- 1907445 TI - Electroporation and conjugal plasmid transfer to members of the genus Aquaspirillum. AB - Electroporation methods and conjugal matings were used to transfer several plasmid vectors to Aquaspirillum dispar and Aquaspirillum itersonii. The incompatibility P class plasmid RP4 was conjugally transferred from Escherichia coli HB101 to these spirilla, and the transconjugants subsequently donated the molecule to plasmid-free E. coli and A. dispar strains via conjugal matings. High voltage electrotransformation was used to transfer plasmids pUCD2, pSa151 and RP4 to A. dispar and A. itersonii, at efficiencies as high as 3 x 10(4) transformants per micrograms plasmid DNA. RP4 DNA isolated from spirillum hosts, but not RP4 from E. coli cells was successfully transferred to A. dispar and A. itersonii by electrotransformation, suggesting that modification and/or restriction activity may be present in these Aquaspirillum species. PMID- 1907447 TI - A prospective study of incisional time, blood loss, pain, and healing with carbon dioxide laser, scalpel, and electrosurgery. AB - Carbon dioxide laser incisions are reported to be less painful, less bloody, and less prone to seroma formation and to heal better than scalpel or electrosurgical incisions. We compared all three modalities in a prospective randomized study of cholecystectomy incisions. Time required for the incision and incisional blood loss was less with electrosurgery than with the carbon dioxide laser or scalpel. Postoperative pain and wound healing, however, were the same for all three techniques. The carbon dioxide laser appears to offer no advantage over conventional means of making a standard incision. PMID- 1907449 TI - [Schistosomal meningoradiculitis: clinico-laboratory study of 3 treated cases]. PMID- 1907448 TI - Monoclonal antibodies to three strains of hantaviruses: Hantaan, R22, and Puumala. AB - Thirty hybrid cell lines that produce monoclonal antibodies to three strains of hantaviruses have been generated and characterized. One clone specific to Hantaan 76-118 strain, four clones specific to Rattus strains and one clone specific to Puumala virus have been identified. Most of the monoclones produced antibodies specific to nucleoproteins. Only two monoclones were found to produce glycoprotein specific, neutralizing antibodies. The immunofluorescent (IFA) staining patterns of the monoclonal antibodies show consistent correlation with viral protein specificities as described for other hemorrhagic fever viruses. Cross-reactivity studies with hantaviruses tested demonstrate conserved antigenic sites on nucleoproteins among these hantaviruses tested. Puumala specific monoclones, produced for the first time, reveal both conserved and strain specific sites on the viral nucleoproteins of the Scandinavian virus. PMID- 1907450 TI - Restricted expression of cardiac myosin light chain 2A gene in muscular dystrophic condition. AB - In order to understand the mechanism of defective myofibrilogenesis in muscular dystrophy, we have used the genomic cloned DNA specific for myosin light chain 2A (MLC 2A) to check its expression. The fusion of a partial digest of lambda LC5, containing the upstream sequence of MLC 2A gene with the expression vector of PSVOCAT has already been reported. Using this CAT-fused recombinant containing 1.6 kb of MLC 2A gene, we were able to detect the promoter activity in normal heart cells, H9C2 cell line whereas a restricted expression of MLC 2A gene was noticed in muscular dystrophic muscle cells from heart and skeletal. We have also measured the transient transfection efficiency by contransfecting with the plasmid LacZ. Simultaneous assay of beta-galactosidase and CAT in the cell extract was performed. With beta-galactosidase as control, we confirmed that the promoter activity of MLC 2A gene is inhibited in muscular dystrophy though there is a normal rate of transfection occurred. PMID- 1907451 TI - [Hybrid human lymphokine genes. I. Design of recombinant plasmids coding hybrids of immune interferon and human tumor necrosis factor]. AB - Recombinant plasmids coding for hybrid proteins between human interferon gamma and human tumour necrosis factor alpha or beta have been constructed using site directed mutagenesis. The genes were fused via a synthetic oligonucleotide linker coding for tetrapeptide Pro-Val-Gly-Pro. The fused genes were expressed in Escherichia coli under control of early promoters of bacteriophage T7. E. coli cells harbouring the plasmids with the hybrid genes gave rather high level of the fused proteins biosynthesis. The hybrid recombinant proteins proved to be unstable in E. coli cells. PMID- 1907452 TI - Immuno-electronmicroscopic demonstration of alpha and beta components of group B streptococcal protein antigen c. AB - Affinity purified and absorbed monospecific antibodies against the protein type antigen c components c alpha and c beta were used in immuno-electronmicroscopic studies. As demonstrated with protein A gold particles the c alpha specific antibodies reacted with the c alpha antigen, the c beta specific antibodies with the c beta antigen. The respective antigens were distributed over the whole surface of the bacterial cells, mainly at the outermost layer of the cell wall. PMID- 1907453 TI - Effect of sub-minimal inhibitory concentrations of ciprofloxacin and fleroxacin on the bacterial capsular antigen and opsonophagocytosis by human polymorphonuclear leukocytes. AB - We have studied the effect of sub-minimal inhibitory concentrations (sub-MIC) of ciprofloxacin and fleroxacin on capsulated (K+) and non-capsulated (K-) Gram negative bacilli (Escherichia coli O1:K1, O7:K1, O1:K-, O7:K-, and Klebsiella oxytoca) as well as on Staphylococcus aureus and we investigated the interaction of antibiotic pretreated bacteria with human serum and polymorphonuclear leukocytes (PMN). Following overnight growth in the presence of 1/2 MIC of the antibiotics, bacteria were opsonized in human serum and incubated with PMN. Opsonophagocytosis was quantified as the ratio of uptake by PMN of radioactively labeled bacteria. Ciprofloxacin and fleroxacin enhanced the phagocytosis rate of E. coli K+ strains (control 5-10%; 1/2 MIC of ciprofloxacin and fleroxacin 70 80%) of K. oxytoca (control O-2%; 1/2 MIC of ciprofloxacin and fleroxacin 35-40%) as well as of Staph. aureus (control 5-10%; 1/2 MIC of the antibiotics 35-40%). Opsonophagocytosis of K- strains was not altered. The enhancement of opsonophagocytosis was a complement dependent process. Exposure of capsulated E. coli to ciprofloxacin as well as to fleroxacin resulted in decreased amounts of the capsular antigen. PMID- 1907454 TI - Effects of antisurfactant antibodies on the course of mild respiratory distress syndrome. AB - The role of surfactant-associated proteins in surfactant function was studied by selectively blocking these proteins with monoclonal antibodies. Four monoclonal antibodies, M1, M2, M3, and M4 were identified and their reactivities examined by Western blot analysis. M1, M2, and M4 bind, respectively, 8-, 10- and both 10- and 34-kD proteins. M3 antibody did not recognize a protein as assayed by this technique. These antibodies were then administered intratracheally to adult rats that had been partially depleted of lung surfactant by broncholavage. None of these antibodies had any deleterious effect on pulmonary function. On the other hand, M4 antibody significantly improved gas exchange. Possible mechanisms by which antibody may effect such improvement are discussed. PMID- 1907455 TI - Nucleotide sequence of the lipase gene lip2 from the antarctic psychrotroph Moraxella TA144 and site-specific mutagenesis of the conserved serine and histidine residues. AB - The lip2 gene from the antarctic psychotroph Moraxella TA144 was sequenced. The primary structure of the Lip2 preprotein deduced from the nucleotide sequence is composed of 433 amino acids with a predicted Mr of 47,222. This enzyme contains a Ser-centered consensus sequence and a conserved His-Gly dipeptide found in most lipase amino-terminal domains. These sequences are involved in the lipase active site conformation since substitution of the conserved Ser or His residues by Ala and Gln, respectively, results in the loss of both lipase and esterase activities. Structural factors that would allow proper enzyme flexibility at low temperatures are discussed. It is suggested that only subtle changes in the primary structure of these psychrotrophic enzymes can account for their ability to catalyze lipolysis at temperatures close to 0 degrees C. PMID- 1907456 TI - Analysis of aversively conditioned learning and memory in rats recovered from pyrithiamine-induced thiamine deficiency. AB - Rats that had recovered from pyrithiamine-induced thiamine deficiency (PTD) were trained on tasks motivated by escape from mild footshock. On postmortem examination, the PTD model showed two consistent lesions: a bilaterally symmetrical lesion of the medial thalamus, which was centered on the internal medullary lamina (IML), and a lesion centered on the medial mammillary nuclei. PTD rats with IML lesions were impaired in learning a spatial nonmatching-to sample (NMTS) task that was mastered without error by controls and PTD animals without IML lesions. These same animals were able to perform as well as controls on discrimination tasks based on either place or visual (light-dark) cues, although they made more errors than controls in reaching criterion in the initial place discrimination problem. These findings are consistent with findings from appetitively motivated tasks that PTD rats with IML lesions have an impaired capacity for working memory but not for reference memory. PMID- 1907457 TI - Impairment of olfactory, auditory, and spatial serial reversal learning in rats recovered from pyrithiamine-induced thiamine deficiency. AB - Rats that had recovered from pyrithiamine-induced thiamine deficiency (PTD) were compared with controls for spatial, auditory, and olfactory serial reversal learning (SRL); spatial matching to sample (MTS); auditory go-no-go discrimination; and open-field exploration. PTD rats made more errors reaching criterion for SRL in all modalities but showed normal transfer effects between problems. PTD rats were also impaired in learning the go-no-go and MTS tasks and showed consistent alterations in exploratory activity. It is argued that the PTD rat, like human Korsakoff patients, have impairments of learning and memory (but spared capacity for reference memory) that extend across sensory modalities. Postmortem analyses showed normal indices of cortical cholinergic, noradrenergic, dopaminergic, and serotonergic function and consistent bilateral lesions of the thalamus, which were centered on the internal medullary lamina, and the medial mammillary nucleus. PMID- 1907458 TI - Response latency and accuracy on a pretrained nonmatching-to-sample task in rats recovered from pyrithiamine-induced thiamine deficiency. AB - Rats were trained for 1,345 spatial nonmatching-to-sample (NMTS) trials, matched, assigned to pyrithiamine-induced thiamine deficiency (PTD) or control treatments, recovered, and re-tested for 400 trials of NMTS. The PTD model produced two bilaterally symmetrical lesions: one of medial thalamus that was centered on the internal medullary lamina (IML) and another involving the mammillary bodies. PTD rats with complete IML lesions showed a sharp drop in performance that persisted throughout posttreatment training. PTD rats with IML sparing were impaired immediately after treatment but improved to a level comparable to that of controls. For all animals, NMTS accuracy decreased for longer latency responses. PTD animals differed from controls primarily in the low frequency and inaccuracy of their short-latency (0-2.9 s) responses. The improvement of the PTD rats with IML sparing was marked by an increase in both the number and accuracy of short latency responses. PMID- 1907460 TI - Inhibition of HIV-1 replication and NF-kappa B activity by cysteine and cysteine derivatives. AB - HIV-1 proviral DNA contains two binding sites for the transcription factor NF kappa B. HIV-1-infected individuals have, on average, abnormally high levels of tumour necrosis factor alpha (TNF alpha) and abnormally low plasma cysteine levels. We therefore investigated the effects of cysteine and related thiols on HIV-1 replication and NF-kappa B expression. The experiments in this report show that cysteine or N-acetylcysteine (NAC) raise the intracellular glutathione (GSH) level and inhibit HIV-1 replication in persistently infected Molt-4 and U937 cells. However, inhibition of HIV-1 replication appears not to be directly correlated with GSH levels. Cysteine and NAC also inhibit NF-kappa B activity as determined by electrophoretic mobility shift assays and chloramphenicol acetyl transferase (CAT) gene expression under control of NF-kappa B binding sites in uninfected cells. This suggests that the cysteine deficiency in HIV-1-infected individuals may cause an over-expression of NF-kappa B-dependent genes and enhance HIV-1 replication. NAC may be considered for the treatment of HIV-1 infected individuals. PMID- 1907459 TI - Zidovudine in the management of primary HIV-1 infection. AB - Eleven subjects who presented with a clinical illness characteristic of primary HIV-1 infection were treated with 1 g zidovudine daily for a median period of 56 days (range, 28-111 days). Primary HIV-1 infection was confirmed in each subject by seroconversion and virus isolation. The acute phase of the illness resolved a median of 4 days (range, 3-14 days) from commencement of zidovudine. Six subjects reported symptoms that may have been side-effects of zidovudine, the most common being nausea in four subjects and headache in two. Treatment was discontinued in one subject who had persistent headache and nausea. Haemoglobin, haematocrit and erythrocyte counts decreased and mean corpuscular volume increased significantly during the treatment. None of the subjects developed anaemia and none required dose modification or blood transfusion as a result of haematological side effects. There were no significant differences in the granulocyte count or the lymphocyte count during any week of treatment when compared with baseline levels. There were no significant differences in T-cell subset numbers of the subjects during treatment compared with a group of historical controls. HIV-1 was isolated from several subjects during and after termination of zidovudine treatment. The results of this investigation indicate that zidovudine is a safe drug to administer to people with primary HIV-1 infection. There was no clear evidence, however, of any clinical benefit in terms of resolution of the acute illness and no indication that the treatment would prevent development of persistent infection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1907461 TI - Direct quantification of HIV-1 infectivity for monocyte--macrophages using an infectious focus assay. AB - Monocyte--macrophages are important target cells and reservoirs for HIV. The existing methods for the quantification of infectious virus in HIV stocks are not totally satisfactory for use with macrophage cultures. We have developed an infectious focus assay for the direct quantification of virions infectious for human peripheral blood monocyte-derived macrophages adhering to plastic microtitre plates. The combination of an HIV-1 p24-antigen-specific monoclonal antibody and a beta-galactosidase-linked second antibody resulted in a sensitive and very specific assay. With 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside as substrate, the assay proved to be as sensitive as p24 antigen quantification in culture supernatants. PMID- 1907463 TI - Detection of HIV-1 RNA in factor VIII concentrate. PMID- 1907462 TI - HIV-1 seropositivity and mortality at University Hospital, Kinshasa, Zaire, 1987. AB - This study examines the impact of HIV-1 infection and AIDS on 500 of 563 consecutive deaths at University Hospital, Kinshasa, Zaire, in late 1987. HIV-1 seroprevalence was 31% for the entire population and 43% for the 247 adults. Forty-two (38%) of the 110 HIV-1-seropositive adult deaths occurred in those between the ages of 25 and 34 years. The mean age of death for seropositives was 36 years, 7.5 years less than seronegative deaths. AIDS and AIDS-associated diagnoses such as cryptococcal meningitis, chronic diarrhea and pneumonia accounted for 42% of all adult deaths and 74% of all HIV-1-seropositive adult deaths. Seventeen per cent of 50 sera initially negative by enzyme-linked immunosorbent assay (ELISA) were ultimately found to be HIV-1-seropositive by Western blot or p24 antigen testing. The data indicate that HIV-1 infection and AIDS contribute significantly to adult mortality in Kinshasa population and that sensitivity of ELISA tests decreases in terminal HIV-1 infection. PMID- 1907464 TI - The ethics of nontreatment of patients with cancers of the head and neck. AB - There are three levels at which nontreatment decisions for patients with cancers of the head and neck might be made: not doing further diagnostic procedures when the data gained would not make a significant difference to treatment decisions; not continuing aggressive therapy when its benefits are outweighed by the ensuing burdens and harms; and, at the policy level, not providing costly aggressive therapy at all because of the number of patients with unmet, more basic needs. These three levels of nontreatment decisions are discussed in light of ethical theory, briefly introduced. Arguments are made in favor of nontreatment decisions at the two clinical levels mentioned above, but against a policy decision to ration treatment for patients with cancers of the head and neck. PMID- 1907465 TI - [Galactosialidosis--clinical feature]. PMID- 1907466 TI - [Neuropathology of galactosialidosis]. PMID- 1907467 TI - [Ocular findings in galactosialidosis]. PMID- 1907468 TI - [Effects of thyrotropin-releasing hormone (TRH) on status epilepticus in rats]. AB - Recent studies have demonstrated that intramuscular administration of thyrotropin releasing hormone (TRH) or its analogue improves various clinical aspects of intractable epilepsy such as Lennox-Gastaut syndrome, West syndrome, and myoclonus epilepsy. Other clinical studies reported efficient property of intravenous TRH against status epilepticus. However, it is also true that intravenous TRH produces epileptic seizures in patients with epilepsy or organic brain damage. Thus, the utility of intravenous TRH for the treatment of status epilepticus seems to be equivocal. To further explore the problem in this regard, we examined the effect of TRH on limbic status epilepticus in rats. Thirty-eight male Wistar rats weighing 180-220g were used. Status epilepticus was induced by intracerebral injection of a combination of 200 micrograms of dibutyryl-cAMP (db cAMP) and 67.2ng of ethylenediaminetetraacetic acid (EDTA) into the amygdala (AM) through an implanted cannula. 30 min later, TRH or vehicle (distilled water) was administered intravenously (i.v.) or intracerebroventricularly (i.c.v.). Although 3 mg/kg of TRH (n = 9), when injected i.v., did not alter the pattern of electroclinical ictal responses induced by db-cAMP/EDTA, 25 mg/kg (n = 5) and 50 mg/kg (n = 5) of TRH significantly exaggerated EEG and/or behavioral ictal seizures, beginning immediately after the injection and lasting for more than 30 min. With 50 mg/kg of TRH, the exaggerated seizure patterns were followed by marked suppression of electroclinical seizures. 50 micrograms of i.c.v. TRH (n = 5), like higher doses of i.v. TRH, caused a slight, but not a significant, build up of electroclinical ictal seizures, beginning immediately after the injection and lasting for about 30 min.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1907470 TI - MR imaging of spinal neurofibromatosis. AB - The MR findings in 7 patients with neurofibromatosis involving the spine were evaluated. Six patients had paraspinal tumors at multiple levels. In 4 they were bilateral. Five patients had multiple intraspinal lesions, frequently with growth through the neural foramen. In one patient paraspinal tumors were found in the lumbar sacral plexus and in another bony dysplasia and meningoceles but no tumors were disclosed. In 2 patients the lesions were associated with bilateral acoustic neuromas and multiple intracranial meningeomas. In one of these a spinal meningeoma with signal characteristics close to spinal cord was found. The other tumors had a signal that was equal to or slightly lower than the spinal cord and slightly higher than muscle on T1-weighted images. On T2-weighted images the tumors had a markedly increased signal compared to surrounding tissue. In 3 patients with tumors larger than 4 cm the signal intensity was inhomogeneous with decreased signal in the center on T2-weighted images, indicating the presence of increased fibrous tissue. Gadolinium-DTPA was given to one patient with marked increase in intensity of small tumors on T1-weighted images. The study shows that MR imaging is the modality of choice for evaluating most aspects of spinal and paraspinal neurofibromatosis. PMID- 1907469 TI - [Analysis of L-threo-3, 4-dihydroxyphenylserine effect on motor and psychological symptoms in Parkinson's disease]. AB - Improvement of motor and psychological symptoms by L-DOPS (L-threo-3,4 dihydroxyphenylserine) in totally 20 cases with Parkinson's disease (PD), including 5 cases of juvenile or early onset parkinsonism (JP) and one case of pure akinesia was analysed. Improvement was obtained in about two thirds of the cases on symptoms of freezing in gait, difficulty of postural control, depressive mood and bradyphrenia. Severity of freezing in gait and that of the depressive mood were graded in five stage (from 0 to 4) scale and the improvement was evaluated by A (three stage improvement), B (two stage improvement), C (one stage improvement) and D (no change or worsened). Improvement of psychological symptoms was seen parallel to that of motor symptoms. It seems important that marked effect on both motor and psychological symptoms was obtained mostly in PD cases but not in the cases of JP. In MMPI test, depressive score (D) and hypochondriac score (Hs) were normalized in PD cases but not changed in JP, indicating differences in psychological traits between two groups. It was suggested that JP is a condition of mainly DA deficiency in nigro striatum but PD presents wider spectrum of symptoms covering both DA and NE deficiency. Importance of the role of aging of the brain in each individual patient is discussed and interpreted in relation to the difference of clinical pictures. PMID- 1907471 TI - Percutaneous gastrostomy. A clinical and experimental study. AB - Fluoroscopic percutaneous gastrostomy for the purpose of nutrition was performed in 28 patients with the aid of a specially designed gastrostomy set. No major complications were reported. Exchange to Foley catheter was performed after 7 days and could be used without complications for the patients' remaining life span. In order to evaluate the formation of a gastrocutaneous tract, an experimental study with the same instruments as in clinical practice was performed in 13 rabbits. Within one week a gastrocutaneous tract was formed, which was possible to dilate for insertion of a balloon catheter of larger size. The described procedure is a simple and time-saving method for a percutaneous gastrostomy in debilitated patients with dysphagia. PMID- 1907473 TI - Growth of Escherichia coli and Salmonella typhimurium on high-pH beef packed under vacuum or carbon dioxide. AB - A strain each of Escherichia coli and Salmonella typhimurium, were inoculated onto samples of high-pH (greater than 6.0) beef. Samples were packaged under vacuum or CO2 and stored at 8, 10, 12, 15, 20 or 30 degrees C. In vacuum packs, E. coli and S. typhimurium grew at all storage temperatures. At temperatures between 8 and 12 degrees C inclusive, both organisms grew at rates less or no more than those of the spoilage flora after significant lag periods. At temperatures of 15 degrees C or above, growth rates were equal to or greater than those of the spoilage flora, and lag periods were insignificant. In CO2 packs, neither organism grew at 8 degrees C, and S. typhimurium did not grow at 10 degrees C. Subsequent tests showed that E. coli did not grow at 9 degrees C, nor S. typhimurium at 11 degrees C. At 12 degrees C, both organisms grew, after prolonged lags, at rates markedly slower than that of the spoilage flora. At 15 degrees C, their growth rates were similar to that of the spoilage flora. At higher temperatures, both organisms grew without significant lags at rates greater than that of the spoilage flora. PMID- 1907472 TI - Antibacterial activity of Lactobacillus sake isolated from dry fermented sausages. AB - Lactic acid bacteria isolated from Spanish dry fermented sausages were screened for antagonistic activities under conditions that eliminated the effects of low pH and hydrogen peroxide. From 720 isolates tested 119 were inhibitory to Lactobacillus fermentum CECT285. The isolates showing the largest inhibitory activity exhibited an antagonistic effect against several other lactobacilli and the selected foodborne pathogens Staphylococcus aureus and Listeria monocytogenes. Comparison of the antimicrobial spectra of the supernatants suggested that the inhibitory compounds were not identical. The isolates were tentatively characterized as Lactobacillus sake. One of the isolates, L. sake 148 was chosen for further study. The compound excreted by L. sake 148 was active against various lactobacilli and several Gram-positive foodborne bacteria, but not against the Gram-negative bacteria tested. The antagonistic effects were almost eliminated by treatment with proteases, whereas they were heat resistant and bacteriostatic rather than bacteriocidal. PMID- 1907474 TI - Adaptation of Listeria in liquid egg containing sucrose resulting in survival and outgrowth. AB - Survival of Listeria species was tested in liquid egg products such as albumen, yolk, whole egg and whole egg containing 25% sucrose. At an incubation temperature of 4 degrees C Listeria survived in all products, and even increased slightly in yolk, whole egg and whole egg containing 25% sucrose. However, at 20 22 degrees C, in whole egg containing sucrose, a rapid an dramatic decrease in numbers of Listeria was observed. Following this initial decrease, an increase in the numbers of Listeria was observed. The ability to grow in liquid egg containing sucrose was maintained upon reinoculation into a freshly prepared product. However, this property disappeared after subculturing in brain heart infusion broth. The significance of these findings is discussed. PMID- 1907475 TI - The effect of Pediococcus damnosus and Pediococcus pentosaceus on the growth of pathogens in minced meat. AB - The antibacterial effects of one strain of Pediococcus damnosus and two strains of Pediococcus pentosacaeus against Clostridium perfringens, Listeria monocytogenes, Salmonella infantis and Yersinia enterocolitica were investigated. Growth inhibition studies were conducted in juice from minced meat incubated at +6 degrees C and +15 degrees C for various periods after the inoculation with pediococci. Inhibitory effects were seen for all bacteria tested. PMID- 1907476 TI - Magnesium in normal and neoplastic cell proliferation: state of the art on in vitro data. AB - Information about the involvement of Mg2+ in all biochemical processes that participate in cell proliferation is reviewed in order to define the role of this divalent cation in normal and pathological growth. The lack of conclusive data about cell Mg2+ homeostasis does not suggest any definitive model for its role in the control of cell proliferation. On the other hand, new important information about its absolute requirement in crucial steps of cell activation that can, beside other functions, trigger cell division, strongly support the involvement of Mg2+ in the control of cell proliferation. Studies on the growth of cells in vitro, however, while confirming the indispensible requirement for Mg2+ in extracellular media, do not completely clarify the mechanism(s) or the exact phase/point of the cell cycle where Mg2+ exerts its regulation. Furthermore, the observation that tumour cells grown in culture are influenced by external divalent cations confirms the involvement of Mg2+ in cancer as well as in normal cell proliferation. The proposed explanations (theories, hypotheses) are described and discussed. PMID- 1907478 TI - TV programme disclaims use of zidovudine. PMID- 1907479 TI - Community nursing: joint enterprise. PMID- 1907477 TI - Platelet-associated IgG in pediatric HIV infection. AB - Hematologic abnormalities, including thrombocytopenia, are seen in HIV infection. We have previously reported elevated platelet-associated IgG (PAIgG) in thrombocytopenia in children associated with human immunodeficiency virus (HIV). In this study we prospectively monitored 40 HIV-infected infants and children to determine the significance of elevated PAIgG levels as they relate to thrombocytopenia. We also examined platelet eluates for the presence of HIV antibody and antigen. Of 16 patients with thrombocytopenia, 15 (93.7%) had elevated PAIgG. Of 24 patients with normal platelet counts, 21 (87.5%) had elevated PAIgG. On follow-up, none of the children with normal platelet counts and elevated PAIgG levels developed thrombocytopenia. Examination of the platelet eluates was negative for HIV antibody or P24 antigen. Although the sensitivity of an elevated PAIgG level in predicting thrombocytopenia is 93%, its specificity is only 13%. Elevated PAIgG levels are therefore not causally related to the development of thrombocytopenia in children. PMID- 1907480 TI - Casualty in action. Interview by Norah Casey. PMID- 1907481 TI - Chronic urinary catheter blockage. AB - Catheter blockage is a common complication of long-term urinary catheterisation which causes distress to the patient and presents management problems for both nursing and medical practitioners. Jennifer Kohler-Ockmore's study aimed to investigate some of the factors which may cause catheter blockage and how they may be overcome. Fifty-four patients, resident in the community, were monitored over a period of six months. The findings revealed that patients were divided into two groups, those with and those without catheter blockage. The only factors identified which differentiated these patients were urinary pH and the incidence of proteus organisms in the urine. The presence or history of bladder stones was also noted among patients who presented with chronic episodes of blockage. PMID- 1907482 TI - Nutrition and the surgical patient. AB - The importance of surgical patients' nutritional status has been clearly established, yet inadequate dietary provision continues to be common in surgical units. Susan Holmes describes the metabolic response to surgery and offers guidance on how the nutritional needs of these vulnerable patients can be met. PMID- 1907483 TI - The advanced nurse practitioner. Part 2. PMID- 1907484 TI - Education: designing a conversion course. AB - Luxmi Narainsingh Gopee describes the development of a conversion course for enrolled nurses in Warwickshire which draws heavily on established academic theory and recommendations from statutory bodies. The first intake of students commenced in June 1990, and while formal evaluations of its effectiveness will not be possible until this cohort has completed the course, initial indications are very encouraging. PMID- 1907485 TI - Community nursing: before I leave town. PMID- 1907487 TI - Malice in wonderland. PMID- 1907486 TI - Community care: over the community fence. PMID- 1907488 TI - A French letter. PMID- 1907489 TI - Community care--for the better? PMID- 1907490 TI - Working mothers--going for the juggler. PMID- 1907491 TI - The GTP-binding Sar1 protein is localized to the early compartment of the yeast secretory pathway. AB - SAR1, the yeast gene which encodes a novel type of small GTP-binding protein, has been shown to be required for protein transport from the endoplasmic reticulum (ER) to the Golgi apparatus. To further the understanding of the function of its product, a lacZ-SAR1 hybrid gene was constructed and a polyclonal antibody was raised against the hybrid protein. This antibody specifically recognizes the SAR1 gene product (Sar1p) as a 23-kDa protein in the yeast cell lysate. We examined the subcellular localization of Sar1p using this antibody. In wild-type cells, Sar1p was predominantly recovered in a rapidly sedimenting membrane fraction that includes the ER. The soluble form of Sar1p was also detected when the protein was overproduced. Immunofluorescence microscopy with the anti-Sar1p antibody showed perinuclear staining that was exaggerated in the ER-accumulating sec18 mutant. Membrane association of Sar1p was shown to be very light. Sar1p was not extracted from the membrane by treatment with alkaline sodium carbonate, and only 1% deoxycholic acid solubilized Sar1p completely. From these results, we suggest that Sar1p is firmly located on the ER membrane where it regulates the ER-Golgi traffic. PMID- 1907492 TI - Galactose effects on enterocyte differentiation in the mouse jejunum. AB - The present work investigates the ability of galactose to affect enterocyte differentiation during normal development in vivo. Energy intake has also been varied to take account of the fact that galactose is poorly metabolized in mice. Brush-border lactase, alpha-glucosidase, dipeptidylpeptidase-IV, aminopeptidase N, alkaline phosphatase and microvillus length were measured as markers of enterocyte differentiation in mice fed diets containing galactose (G diet), corn oil (E diet) or galactose + corn oil (G + E diet). Maintaining mice on a G instead of E diet reduced brush-border lactase activity and enterocyte migration rates; alpha-glucosidase, dipeptidylpeptidase-IV, aminopeptidase N and microvillus length expression increased and alkaline phosphatase activity remained unchanged. Feeding the G + E diet restored enterocyte migration rates, lactase, aminopeptidase N and dipeptidylpeptidase-IV activities to values found in mice fed the E diet. Galactose stimulation of alpha-glucosidase and microvillus length expression was, however, fully maintained in mice fed the G + E diet. Present results show that enterocyte differentiation is affected independently by varying dietary galactose and energy levels; that galactose effects always increase and energy effects usually decrease expression of enterocyte components and that energy stimulation of lactase activity is exceptional. PMID- 1907493 TI - Characterization of cytosolic pertussis toxin-sensitive GTP-binding protein in mastocytoma P-815 cells. AB - We have characterized a soluble pertussis toxin (PT)-sensitive GTP-binding protein (G-protein) present in mouse mastocytoma P-815 cells. 65% of total ADP ribosylation of PT substrate having a molecular mass of 40 kDa on SDS polyacrylamide gel electrophoresis in cell homogenate was detected in the supernatant after centrifugation at 100,000 x g for 90 min. [32P]ADP-ribosylation of cytosolic PT substrate was significantly enhanced on the addition of exogenous beta gamma complex. The molecular mass of the cytosolic PT substrate was estimated to be about 80 kDa on an Ultrogel AcA 44 column, but the beta gamma complex was not detected in the cytosol by using the anti-beta gamma complex antibody. Furthermore, the cytosolic PT substrate was found to have some unique properties: [35S]GTP gamma S binding was not inhibited by GDP and [32P]ADP ribosylation was not affected by GTP gamma S treatment. Only after the cytosolic PT substrate had been mixed with exogenous beta gamma complex, did it copurify with exogenous beta gamma complex by several column chromatographies including an Octyl-Sepharose CL-4B column. The PT substrate was identified as Gi2 alpha by Western blot analysis and peptide mapping with S. aureus V8 protease. These results suggest that Gi2 alpha without beta gamma complex exists with an apparent molecular mass of about 80 kDa in the cytosolic fraction of P-815 cells. PMID- 1907495 TI - [Adhesiveness in Neisseria meningitidis. A virulence factor?]. AB - The role of adhesivity as a factor of virulence in cases of N. meningitidis has not yet been established. Unlike other bacteria in which the presence of adhesivity reflects an enhanced virulence, a high capacity of adherence is associated with a low virulence and invasive capacity in cases of meningococcus. In order to gain more insight into the knowledge of this phenomenon we have studied the adhesivity of 109 strains of N. meningitidis to human pharyngeal epithelial cells. Twenty nine out of the 109 strains were isolated from blood or spinal fluid of patients with meningococcal infection (meningitis or septicemia), whereas the remaining 80 strains were obtained from pharyngeal smears of healthy carriers. The adhesivity was measured as the number of meningococci adhered to 50 epithelial cells according to Craven's scale. Strains of healthy carriers showed a greater adhesivity than that of patients (p less than 0.001). The relevance of the pharyngeal area in the evaluation of the adhesive capacity is in accordance with the hypothesis that meningococcal adhesivity decreases when the microorganism crosses the pharyngeal epithelium. The results would support the concept that the virulence of N. meningitidis is related to its adhesiveness. PMID- 1907494 TI - Homologous and unique G protein alpha subunits in the nematode Caenorhabditis elegans. AB - A cDNA corresponding to a known G protein alpha subunit, the alpha subunit of Go (Go alpha), was isolated and sequenced. The predicted amino acid sequence of C. elegans Go alpha is 80-87% identical to other Go alpha sequences. An mRNA that hybridizes to the C. elegans Go alpha cDNA can be detected on Northern blots. A C. elegans protein that crossreacts with antibovine Go alpha antibody can be detected on immunoblots. A cosmid clone containing the C. elegans Go alpha gene (goa-1) was isolated and mapped to chromosome I. The genomic fragments of three other C. elegans G protein alpha subunit genes (gpa-1, gpa-2, and gpa-3) have been isolated using the polymerase chain reaction. The corresponding cosmid clones were isolated and mapped to disperse locations on chromosome V. The sequences of two of the genes, gpa-1 and gpa-3, were determined. The predicted amino acid sequences of gpa-1 and gpa-3 are only 48% identical to each other. Therefore, they are likely to have distinct functions. In addition they are not homologous enough to G protein alpha subunits in other organisms to be classified. Thus C. elegans has G proteins that are identifiable homologues of mammalian G proteins as well as G proteins that appear to be unique to C. elegans. Study of identifiable G proteins in C. elegans may result in a further understanding of their function in other organisms, whereas study of the novel G proteins may provide an understanding of unique aspects of nematode physiology. PMID- 1907496 TI - [Infections caused by Corynebacterium group 2]. PMID- 1907497 TI - [Bacteremia and spontaneous peritonitis caused by N. meningitidis serogroup B in a cirrhotic patient. Measurement of the levels of complement]. PMID- 1907498 TI - [Resistance to pyrazinamide in tuberculosis patients]. PMID- 1907499 TI - Evaluation on HIV serology and immune-stimulation on patients in Tanzania. AB - Antibodies against human immunodeficiency virus, other infectious agents and neopterin levels were determined in 253 patients in a rural area of North-West Tanzania. Seroprevalence for HIV was 3.2%. In one case serology was positive for HIV-1 and HIV-2 antibodies and questions whether there was a real double infection or a cross reaction not only concerning core region proteins but also transmembrane protein. The specificity in the diagnosis of HIV-infection is markedly increased with newer serological methods using recombinant peptides but did not improve sensitivity on African sera. Neopterin was determined as a sensitive indirect marker for the activation of T-cells and is therefore correlated with the susceptibility of HIV infection and with progression of disease. High seroprevalence rates for various infectious agents were determined and may explain the high rate of elevated neopterin levels in 80% of the Africans. Neopterin levels were even higher in HIV patients. Viral p24 antigen was found only in two persons, one of whom had no antibodies detectable. PMID- 1907500 TI - Gonorrhoea and urogenital chlamydial infection in female prostitutes in Tegucigalpa, Honduras. AB - The prevalence of gonorrhoea and urogenital chlamydial infection was investigated in female prostitutes in Tegucigalpa, Honduras. Epidemiological data were recorded according to a standardized questionnaire. The median age of the prostitutes was 27 years and the median period of prostitution was 2-4 years. Most of the women (91%) had no occupation other than prostitution and 57% of them had not even completed primary school. In 233 cases when both gonococcal culture and chlamydial antigen detection with a commercial EIA kit were performed the prevalence of gonorrhoea was 25% (59) and that of chlamydial infection 31% (72). Both diseases were recorded in 9%. The women who had been prostitutes for 2 years or longer had gonorrhoea (P less than 0.01) or chlamydial infection (P less than 0.05) less frequently than those who had practised prostitution for a shorter time period. Among 70 different gonococcal isolates from 241 prostitutes, 40 (57%) belonged to serogroup W II/III. Most (83%) of the 30 W I isolates were beta lactamase producing (PPNG) like 42% of the W II/III isolates. All non-PPNG isolates, except one had decreased susceptibility to benzylpenicillin (MIC greater than or equal to 0.125 mg/l) and all isolates were susceptible to spectinomycin. Four out of five isolates from the throat were PPNG and the fifth had a benzylpenicillin MIC of 0.5-2.0 mg/l. PMID- 1907501 TI - Early aggressive management of cryptosporidial infection in AIDS. AB - We report two cases of cryptosporidiosis in patients with the acquired immunodeficiency syndrome (AIDS) which responded to early intervention with intravenous zidovudine and total parenteral nutrition (TPN). PMID- 1907502 TI - [Interaction of phosphorylase kinase with thin filament proteins of rabbit skeletal muscles]. AB - The binding of phosphorylase kinase to thin filaments and their effects on the enzyme activity as well as the contribution of the enzyme to contractile protein phosphorylation have been studied. The data obtained suggest that the kinase binding to thin filaments is controlled by the regulatory proteins, troponin and tropomyosin. The bulk of the enzyme is bound to the F-actin-tropomyosin-troponin complex which activates the enzyme in a far greater degree than each of its constituent components. Ca2+ and ATP control the kinase binding to F-actin. ATP increases the enzyme binding 6-fold; Ca2+ decrease the S0.5 value for F-actin 5 fold. In acetone powder extracts phosphorylase kinase phosphorylates thin filament-bound phosphorylase b, troponin T and troponin I as well as 51-58 kDa and 114 kDa proteins. These results suggest that phosphorylase kinase plays a role in the mechanism of synchronization of glycogenolysis and muscle contraction rates. PMID- 1907503 TI - [Effect of o-benzoquinone derivatives on free radical processes, induced in rat liver microsomes by carbon tetrachloride]. AB - The effect of o-benzoquinones on free radical reactions stimulated in rat liver microsomes was studied by using 14C-labeled CCl4. It was found that o benzoquinones decrease the amount of 14C from CCl4 covalently bound to proteins and lipids. This effect may be due to both decontamination of free radical products of CCl4 metabolism and to inhibition of their synthesis by a shunt via the NADPH-dependent electron transport chain of microsomes. There is evidence that under conditions of ClC4 poisoning the protective effect of o-benzoquinones correlates with their ability to inhibit the covalent binding. It is concluded that covalent binding plays the key role in CCl4 hepatotoxicity. PMID- 1907504 TI - [Effect of temperature and pH on the stability and catalytic activity of the serine proteinase from Bacillus subtilis strain 72]. PMID- 1907505 TI - [Isolation of GTP-binding Gs-protein liberated from human erythrocyte membranes under the action of fluoride ions]. AB - Human erythrocyte membranes were incubated in the presence of sodium fluoride. After centrifugation at 30,000 g for 30 min the supernatant was able to stimulate the catalytic subunit of adenylate cyclase. The stimulatory factor was purified from the supernatant of fluoride-treated membranes by three subsequent chromatographic steps including DEAE-Sephacel ion-exchange chromatography in the absence of detergent, gel-filtration on Ultrogel AcA 44 in the presence of 1% sodium cholate and phenyl-Sepharose CL/4B hydrophobic chromatography. The final preparation showed approximately 120-fold purification in stimulatory activity over the initial extract and contained two polypeptides (Mr 42 kDa and 36 kDa). The stimulator activity of the preparation was inhibited by 60% by beta gamma subunits of the GTP-binding protein of bovine brain membranes, G0. The data obtained suggest that the regulatory GTP-binding stimulatory protein of adenylate cyclase, GS, dissociates from human erythrocyte membranes as a result of fluoride ion treatment. PMID- 1907506 TI - [O2 uptake and CO2 production during total intravenous propofol-alfentanil anesthesia under steady-state conditions. Is O2 uptake a parameter for assessing the depth of anesthesia?]. AB - Depending on surgical and anaesthesiological procedures, anaesthesia leads to a reduction of O2 uptake (VO2), CO2 production (VCO2) and resting energy expenditure (REE). A controversial discussion on the degree of metabolic depression has continued in the literature fueled by a lack of studies in patients under standardised conditions. The goal of this study was to evaluate whether O2 consumption and/or CO2 production can be correlated to various depths of anaesthesia and whether VO2 could be a parameter to control narcosis. 12 patients (ASA I-II) scheduled for urological surgery of the lower abdomen, were given total intravenous anaesthesia with propofol and alfentanil. During a 60 minutes period the patients were first anaesthesized with an ED50 and then titrated to a dosage correlating with an ED95. The premedicated but awake patients each showed a REE which was about 10% below the calculated basal metabolism. Steady-state general anaesthesia led to an approximately 30% reduction of VO2, VCO2 an REE. Patients with adequate anaesthesia revealed no changes in oxidative metabolism with increased or decreased depth of anaesthesia. VO2 as a leading parameter proves to be problematic. It is useful as a measure for insufficient depth of general anaesthesia but fails to indicate overshooting anaesthesia depth. PMID- 1907507 TI - Conformational preference and ligand binding properties of DNA junctions are determined by sequence at the branch. AB - Four-arm DNA branched junctions are stable analogues of Holliday recombinational intermediates. A number of four-arm DNA junctions synthesized from oligonucleotides have now been studied. Gel mobility or chemical footprinting experiments on several immobile four-arm junctions indicate that in the presence of Mg2+, they assume a preferred conformation consisting of two helical domains, each formed by stacking a particular pair of arms on each other. We show here that a junction we designate as J1c that has the same chemical composition as one we have previously studied in detail, J1, but is formed from the four strands complementary to those of the latter, exhibits the reverse stacking preference. The pattern of self-protection of the strands of J1c exposed to Fe(II).EDTA induced scission reveals that twofold symmetry is preserved, but the opposite pair of strands preferentially cross over. Moreover, the Fe(II).EDTA scission profiles of J1c indicate that this junction exhibits a weaker bias as to which strands cross over than is observed in J1. The preference for the dominant species in J1 is 1.3 times greater than in J1c at 4 degrees C and in the presence of 10 mM Mg2+, based on chemical reactivity data. This is confirmed by a cleavage experiment using the resolvase enzyme, endonuclease I, from bacteriophage T7. This difference could reflect either sequence-dependent differences in the equilibrium among isomers, or in the structure of these junctions. Chemical footprinting experiments using the probes MPE.Fe(II) and (OP)2Cu(I) show that the high-affinity ligand binding site in immobile junctions is determined by junction geometry. PMID- 1907508 TI - Cost effectiveness of a training program for dementia carers. AB - An intensive 10-day residential training program for dementia carers has previously been shown to be associated with increased patient survival at home and decreased psychological morbidity in carers (Brodaty & Gresham, 1989). Results from a further follow-up, about 39 months after entry into the trial, were even more impressive. Patients whose carers had trained in the program had much higher adjusted rates of survival at home (53% versus 13%) and, unexpectedly, fewer deaths (20% versus 41%) than those whose carers did not have training. Patients whose carers had delayed training achieved intermediate results (31% surviving at home and 21% dying). These results were achieved with an average saving of $A7,967 ($U.S.5975) per patient over the first 39 months. PMID- 1907509 TI - Amino acid composition of band 3 protein from red blood cells of normal and epileptic children. AB - Amino acid analyses of the band 3 protein purified from erythrocyte membranes of control and epileptic children showed that no major structural abnormalities of this protein could be linked with the red blood cell membrane alterations previously described in child epilepsy and, consequently, the molecular basis of these alterations should be looked for elsewhere. PMID- 1907510 TI - The molecular basis of resistance to the herbicide norflurazon. AB - We have cloned and sequenced a gene, pds, from the cyanobacterium Synechococcus PCC7942 that is responsible for resistance to the bleaching herbicide norflurazon. A point mutation in that gene, leading to an amino acid substitution from valine to glycine in its polypeptide product, was found to confer this resistance. Previous studies with herbicide-resistant mutants have indicated that this gene encodes phytoene desaturase (PDS), a key enzyme in the biosynthesis of carotenoids. A short amino acid sequence that is homologous to conserved motifs in the binding sites for NAD(H) and NADP(H) was identified in PDS, suggesting the involvement of these dinucleotides as cofactors in phytoene desaturation. PMID- 1907512 TI - Primary structure of the psbN-psbH-petC-petA gene cluster of the cyanobacterium Synechocystis PCC 6803. PMID- 1907511 TI - Nucleotide and derived amino acid sequence of the cyanogenic beta-glucosidase (linamarase) from white clover (Trifolium repens L.). AB - The nucleotide sequence and derived amino acid sequence of two different beta glucosidase cDNA clones were determined. One clone (TRE104) was identified as the cyanogenic beta-glucosidase by homology with the N-terminal and internal peptide amino acid sequence of the purified enzyme. The biological function of the other beta-glycosidase (TRE361) is not known. Co-segregation of genomic restriction fragments uniquely identified by each cDNA clone shows that these two genes are linked in the white clover genome. Both TRE104 and TRE361 fragments co-segregate with cyanogenic beta-glucosidase activity. Extensive homology was found between the white clover beta-glucosidase sequences and a group of prokaryote and mammalian beta-glycosidases. This group of sequences has no homology with a separate set of beta-glucosidase genes isolated from fungi and the thermophilic bacterium Clostridium thermocellum. PMID- 1907513 TI - Levels of organochlorine pesticides and polychlorinated biphenyls (PCBs) in human milk and serum collected from lactating mothers in the northern Adriatic area of Yugoslavia. PMID- 1907514 TI - Pesticide transmission in fabrics: effect of particulate soil. PMID- 1907515 TI - Correlation between burrowing capability and AChE activity in the earthworm, Pheretima posthuma, on exposure to carbaryl. PMID- 1907516 TI - Serum osteocalcin levels are decreased in patients with acute viral hepatitis. AB - In 16 patients with acute viral hepatitis and 32 sex- and age-matched control subjects the serum levels of osteocalcin, a biochemical parameter of bone formation, as well as the serum levels of parathyroid hormone, 25-hydroxyvitamin D, calcium and phosphorus were measured. The serum levels of osteocalcin (P less than 0.0001) and parathyroid hormone (P less than 0.0001) were significantly lower when measured at the time of maximal aminotransferase levels in the patients with hepatitis than in the control subjects. In contrast, the serum levels of calcium and 25-hydroxyvitamin D were similar in the patients and the controls. In nine patients with acute hepatitis measurements of the biochemical bone metabolism parameters were performed after normalization of the liver enzymes. In these patients a significant increase of serum osteocalcin levels towards normal values (P less than 0.0005) was found, parathyroid hormone levels tended to increase. Our data suggest an alteration of bone metabolism in patients with acute viral hepatitis. Bone formation as reflected by serum osteocalcin levels seems to be decreased in acute hepatitis and returns to normal after recovery from hepatitis. PMID- 1907517 TI - A critical evaluation of monkey models of amnesia and dementia. AB - In this review we consider various models of amnesia and dementia in monkeys and examine the validity of such models. In Section 2 we describe the various types of memory tests (tasks) available for use with monkeys and discuss the extent to which these tasks assess different facets of memory according to present theories of human memory. We argue that the rules which govern correct task performance are best regarded as a form of semantic rather than procedural memory, and that when information about stimulus attributes or reward associations is stored long term then that knowledge is semantic. The demonstration of episodic memory in monkeys is problematic and the term recognition memory has been used too loosely. In particular, it is difficult to dissociate episodic memory for stimulus events from the use of semantic memory for the rule of the task, since dysfunction of either can produce impairment on performance of the same task. Tasks can also be divided into those which assess memory for stimulus-reward associations (evaluative memory) and those which tax stimulus-response associations including spatial and conditional responding (non-evaluative memory). This dissociation cuts across the distinction between semantic and episodic memory. In Section 3 we examine the usefulness of the classification of tasks described in Section 2 in clarifying our understanding of the contribution of the temporal lobes and the cholinergic system to memory. We conclude that evaluative and non-evaluative memory are mediated by separate parallel systems involving the amygdala and hippocampus, respectively. PMID- 1907518 TI - Drug metabolizing enzymes in the brain and cerebral microvessels. AB - Several families of brain parenchyma and microvessel endothelial cell enzymes can metabolize substrates of exogenous origin. This xenobiotic metabolism includes functionalization and conjugation reactions and results in detoxication, but also possibly in the formation of pharmacologically active or neurotoxic products. The brain is partially protected from chemical insults by the physical barrier formed by the cerebral microvasculature of endothelial cells, which prevents the influx of hydrophilic molecules. These cells provide also, as a result of their drug metabolizing enzyme activities, a metabolic barrier against penetrating lipophilic substances. The involvement of these enzymatic activities in neurotoxic events, probably responsible for neuronal dysfunctioning and/or death, neurodegenerative diseases and normal aging, is discussed. PMID- 1907519 TI - Acquired hypoprothrombinaemia and lupus anticoagulant: response to steroid therapy. AB - An iliac crest bone marrow aspiration in a 24-year-old man was followed by severe haemorrhage into the iliopsoas muscle. A lupus anticoagulant and severe hypoprothrombinaemia, as well as clinical and laboratory pointers to suggest the presence of a systemic lupus erythematosus-like syndrome, were demonstrated. Therapy with prednisone was commenced following recurrent severe epistaxis. His prothrombin time, activated partial thromboplastin time and prothrombin activity improved promptly and his bleeding ceased. The lupus anticoagulant is commonly encountered in the laboratory, but acquired hypoprothrombinaemia is extremely rare. The condition is reviewed and its treatment discussed. PMID- 1907520 TI - [Arrhythmogenic risk of antiarrhythmic drugs: study with class Ic drugs during myocardial ischemia]. AB - The effects of three Ic antiarrhythmic drugs were investigated in anaesthetized, open-chest pigs, in a left ventricular area under pacing at constant high (180/min) rate, outside and during an ischaemia produced by temporary complete occlusion of the left anterior descending coronary artery, 1-1.5 cm from its origin. In addition to surface ECG, conduction time and monophasic action potential were recorded in the contractile fibres. Measurement of effective refractory period was added outside the periods of ischaemia. In this event, flecainide and propafenone, in 2.5 mg/kg dose, and cibenzoline, in 2.0 mg/kg dose, i.v. injected, lengthened considerably (50 to 90%) conduction time, but did not affect or hardly affected monophasic action potential and effective refractory period. During ischaemia, they did not hinder the abbreviation of monophasic action potential (30%) and reduced to a large extent (about 120 to 25 s) the onset time of fibrillation. The profibrillatory effect of Ic antiarrhythmic drugs, certainly more pronounced than those of other antiarrhythmic drugs, might be explained by their potent action on depolarization of the contractile fibres coincident with an almost total absence of action on repolarization. PMID- 1907521 TI - [Orientation and stretching of DNA chains during pulsed field gel electrophoresis]. AB - The quantitative analysis of the decay of birefringence accompanying gel electrophoresis leads to the characterization of two phenomena respectively attributed to alignment of the tube and to overstretching of the chain in its tube. The major contribution to the molecular orientation is given by the overstretching which relaxes according to a stretched exponential law. The other process, slow, is characterized by a reptation time and a mean orientation factor in good agreement with the biased reptation model without overstretching. PMID- 1907522 TI - [Long-term induced effects by only one treatment with ketoconazole on rat tumoral pituitary cells (GH3/B6 strains)]. AB - Ketoconazole, an imidazole is a powerful antimycotic that has recently been used in the treatment of endocrinological and lipid metabolism disorders as well as in anti-cancer chemotherapy. When rat mammosomatotropic cells are treated for 30 hrs., this drug produces different effects depending on whether cells are normal or tumoral (GH3/B6). A dose of 10 microM had no effect in normal cells, however, in tumoral cells it had dramatic effects: (i) 50% of the cells are killed and those which survive no longer proliferate and they secrete GH but not PRL; (ii) they respond to GHRH in a dose-dependent manner, while normal cells do not under similar culture conditions; (iii) the lipid composition of the membrane is modified as indicated by the increase in arachidonic acid turn-over and the dramatic change in the distribution of its metabolites. For the moment we cannot explain these data. PMID- 1907523 TI - [Increase by FSH hormone and depression by testosterone of the diffusional coupling between Sertoli cells from immature rat testis in primary culture]. AB - Previous studies have suggested that FSH promotes the intercellular coupling of Sertoli cells from immature rat testis in primary culture ([1], [2]). In order to test this hypothesis, we have investigated the diffusional coupling between Sertoli cells in primary culture with the FRAP technique. The coupling is low in unstimulated cells but increases in the presence of FSH. This effect is not reversed by returning to the control medium. Testosterone decreases this coupling, an effect which is reversed by a new exposure to FSH. Taken together these data show that FSH initiates diffusional coupling in Sertoli cells and that testosterone antagonizes this effect. PMID- 1907524 TI - Toxic effects of drugs used in the ICU. Nitroprusside, nitroglycerin, and angiotensin-converting enzyme inhibitors. AB - Sodium nitroprusside causes cyanide poisoning at currently recommended infusion rates. Serum thiocyanate concentrations are of no value in detecting cyanide poisoning caused by nitroprusside. Methemoglobinemia in those patients receiving intravenous nitroglycerin may seriously impair oxygen delivery and is not always accompanied by cyanosis in anemic patients. Angiotensin-converting enzyme inhibitors are responsible for a plethora of adverse effects, including renal insufficiency, hypotension, angioedema, cough, and increased insulin sensitivity. PMID- 1907525 TI - Toxicities of parenteral nutrition in the critically ill patient. AB - Critically ill patients have unique nutritional substrate requirements. Although important advances have been made in understanding these requirements in the face of pathophysiologic and biochemical alterations induced by stress or trauma, nutrition-associated toxicities still occur. The importance of these toxicities to the critically ill patients cannot be over-stated. Many of these toxicities can be avoided by conservative use of selected nutrition substrates in specific subsets of the critically ill population. Practitioners must continue to anticipate and recognize parenteral nutrition-associated toxicities, however, as well as delineate any toxicity from the progression or exacerbation of disease. PMID- 1907526 TI - Molecular study in von Recklinghausen neurofibromatosis (NF1). AB - The von Recklinghausen neurofibromatosis (NF1) gene has been mapped to the pericentromeric region of chromosome 17 and various DNA markers have been identified in this region. We have performed a genetic analysis using an anonymous DNA marker, HHH202 (D17S33), tightly linked to the NF1 gene in seven NF1 Italian families. Only one family was fully informative for the HHH202/RsaI polymorphism. In this family this marker can be used for presymptomatic and prenatal diagnosis. However, it is necessary to use additional flanking markers in order to increase informativeness and to obtain better diagnostic accuracy. PMID- 1907527 TI - Nitrendipine does not impair long-term glucose control in hypertensive noninsulin dependent diabetic patients. AB - The subjects, 15 noninsulin-dependent diabetic hypertensive patients (mean age, 61 years) and 15 nondiabetic hypertensive patients (mean age, 60 years), received placebo for four weeks and then 20 to 40 mg of nitrendipine once daily for 24 weeks. At the end of the placebo period their blood pressures were greater than or equal to 160 mmHg systolic or greater than or equal to 95 mmHg diastolic. Blood pressures declined significantly during treatment in both patient groups; after 24 weeks, 13 of 15 diabetic patients and 12 of 15 nondiabetic patients were normotensive (diastolic blood pressure less than 90 mmHg). Meanwhile, heart rate, indices of glycemic control (serum glucose, hemoglobin A1c, fructosamine, and C peptide levels), and serum lipids (cholesterol, high-density cholesterol, triglycerides, apolipoprotein A1 and B levels) did not change. It is concluded that nitrendipine does not impair glucose or lipid metabolism in diabetic hypertensive patients. PMID- 1907528 TI - Effects of polydextrose on serum lipids, lipoproteins, and apolipoproteins in healthy subjects. AB - The subjects were 61 healthy volunteers who received 15 gm of polydextrose daily for two months. A significant increase in the incidence of soft feces and diarrhea and in the volume of feces was reported during polydextrose treatment. These had returned to normal one month after treatment. Serum levels of total cholesterol, triglycerides, and low-density lipoprotein cholesterol did not change during treatment. Levels of apolipoprotein (apo) A-I and A-II were significantly lowered at one month and high-density lipoprotein cholesterol (HDL C) and apo A-I were significantly decreased at two months; these returned to normal after treatment. Levels of HDL2-C decreased and HDL3-C levels increased significantly during treatment. The results indicate that polydextrose selectively affected the metabolism of HDL and its major proteins, apo A-I and A II. PMID- 1907529 TI - [Study on periodically prevalent feature for epidemic cerebrospinal meningitis in China]. AB - A study on periodically prevalent feature for epidemic cerebrospinal meningitis (ECM) in China was carried out by means of cluster analysis of multilocus enzyme electrophoresis, as well as chromosomal DNA fingerprinting and subserotyping of outer membrane protein class 1 of Neisseria meningitidis group A. Two hundred strains tested were isolated from the patients for ECM and carriers during the 1960s to 1980s in 17 provinces and municipalities. Overall analysis on the bacterial types of the strains above mentioned and data of morbidity of this disease for recent 40 years was undertaken. The research results indicated that ECM really possessed the feature of cyclic prevalence in China, the cyclic epidemics were caused by the different predominant types of Neisseria meningitidis group A and the strains of predominant types could be periodically spread. Every epidemic was basically spread from the north to the south of China. However, the patterns of cyclic epidemic of this disease were not uniform in the country. The above study has established the preliminary base to reveal the prevalent mechanism for ECM by use of molecular biological methods in China. PMID- 1907530 TI - Cytokine production by peripheral blood mononuclear cells in IgA nephropathy. AB - The regulation of cytokine production and T cell proliferation by other cytokines is mandatory in mediating inflammatory responses but the full understanding is far from complete. We have previously reported increased production of IL-2 and IL-2 receptors (IL-2R) in IgA nephropathy. The present study was undertaken to examine other cytokine production during T cell activation in IgA nephropathy. Peripheral blood mononuclear cells (PBMC) from 17 IgA nephritic patients and 14 controls were cultured with phytohaemagglutinin and phorbol myristate acetate for 48 h for maximal cytokine production. IL-2Rs and IL-4 receptors (IL-4Rs) expressed on cultured PBMC were studied by a radioimmunoassay using monoclonal antibodies against these receptors. Although the total cellular IL-2R expression and percentages of T helper and T suppressor cells did not differ between the patients and controls, there was a significant increase in activated T helper cells expressing IL-2R in patients with IgA nephropathy. The total cellular IL-4R expression was elevated in IgA nephritic patients (P less than 0.005). IL-2 production by PBMC was raised in IgA nephritic patients compared with controls (P less than 0.05) but no difference in IL-4 or IL-6 production was observed. The interferon-gamma production by PBMC was significantly increased in patients with IgA nephropathy (P less than 0.025). No correlation was observed between individual cytokine levels. Our data suggest there are selective increases in cytokine production in IgA nephropathy. PMID- 1907531 TI - Recombinant interferon-gamma inhibits the expression of IL-4 receptors on human lymphocytes. AB - Interferon gamma (IFN-gamma) has been shown to inhibit many of the activities of IL-4, including the induction of IgE synthesis and the proliferation of T cell clones. Here we demonstrate that IFN-gamma is able to inhibit the expression of IL-4 receptors on peripheral blood lymphocytes from both normal healthy donors and from patients with chronic lymphocytic leukaemia. Inhibition was shown to be dose-dependent and did not affect the binding affinity of the receptor as shown by Scatchard analysis. IFN-gamma was unable to displace labelled IL-4 from its membrane receptor, which demonstrates that IFN-gamma and IL-4 do not compete for the same membrane binding protein. The ability of IFN-gamma to down-regulate IL-4 receptors may be important in controlling certain immune responses. PMID- 1907532 TI - Cellular origins of human polymeric and monomeric IgA: enumeration of single cells secreting polymeric IgA1 and IgA2 in peripheral blood, bone marrow, spleen, gingiva and synovial tissue. AB - Using modified ELISA and spot-ELISA, which permit the parallel determination of heavy chain subclass and the presence of covalently linked J chain, we analysed IgA found in cell culture supernatants or secreted by individual cells from peripheral blood, spleen, bone marrow, gingiva and synovial tissue, with respect to its polymeric or monomeric IgA form (pIgA, mIgA) and IgA1 or IgA2 subclass. The ELISA for determination of J chain in tissue culture supernatants was specific and highly sensitive (detection limit in pg). The results demonstrated that IgA1-producing cells predominated in the tissues examined, and that J chain could be detected in association with the majority of IgA1 and IgA2 secreted by individual cells. With respect to the frequency of cells secreting polymeric, J chain-containing IgA, only 20-30% of cells from the bone marrow were engaged in the synthesis of PIgA. In other tissues the frequency of cells secreting pIgA1 and pIgA2 was considerably higher. Peripheral blood mononuclear cells secreting pIgA2 were easily inducible during stimulation with T cell-dependent pokeweed mitogen, whereas Epstein-Barr virus-transformed cells secreted preferentially mIgA1. When the frequencies of pIgA-, pIgA1- or pIgA2-secreting cells (determined by spot-ELISA technique) from different tissues were correlated with the proportion of pIgA to mIgA (and IgA subclasses) secreted in tissue culture supernatants, data obtained suggest that many individual IgA-producing cells could be engaged in simultaneous secretion of mIgA and pIgA. PMID- 1907533 TI - Strain differences in mouse cellular responses to Mycobacterium lepraemurium and BCG subcutaneous infections. II. Production of interleukins 2, 4, and 6 and of interferon-gamma by draining lymph node cells. AB - C57BL/6, BALB/c, and CBA mice were infected either by Mycobacterium bovis BCG or by M. lepraemurium (MLM). Interleukins (IL) 2, 4 and 6 and interferon-gamma (IFN gamma) were measured in the supernatants of draining lymph node cells (DLN) or control lymph node cells from uninfected mice, restimulated in vitro by the heat killed infecting Mycobacterium. Uninfected lymph node cells did not develop any IL4, IL2, and IFN-gamma response to BCG and MLM. A significant IL6 response to BCG was observed, with CBA being the best producer and C57BL/6 the weakest. BCG infected mice, which controlled the BCG infection, displayed variable patterns of lymphokine response to BCG according to the strain. C57BL/6 DLN cells produced more IL6 and IFN-gamma than IL2, whereas BALB/c mice produced more IL2. CBA secreted lymphokines with a similar pattern to that of BALB/c but in lower amounts. IL4 was not detected in any supernatant. MLM-infected mice displayed variable susceptibilities to MLM infection: C57BL/6 was resistant, BALB/c was susceptible after an initial efficient control, and CBA was fully susceptible. In each strain the lymphokine response to MLM was much lower than that triggered by BCG, but the pattern was similar. Thus, C57BL/6 DLN cells still produced significants amounts of IL2, IL6, and IFN-gamma, whereas BALB/c secreted IL2 alone and CBA did not produce any detectable lymphokine. IL4 was again not detected in any supernatant. The failure of BALB/c and CBA strains to develop IFN gamma and IL6 responses to MLM might contribute to their low resistance to this infection. PMID- 1907534 TI - Hurler syndrome with special reference to histologic abnormalities of the growth plate. AB - Hurler syndrome is a mucopolysaccharide disorder resulting from an heritable deficiency in alpha-L-iduronidase, an enzyme required in the catabolism of heparan sulfate and dermatan sulfate glycosaminoglycan (GAGs). The resultant intracellular accumulation of GAG leads to disruption of the intracellular and extracellular environment and dysfunction of multiple organ systems. Among the most noted manifestations of this disease is disproportionate short trunk dwarfism, which develops during the first years of life. Histochemical and electron-microscopic observations on a 30-month-old child with Hurler syndrome showed marked irregularities in chondrocyte orientation within the growth plate, along with disruption of the normal columnar architecture. Vacuolization with enlargement of the cellular border was the characteristic ultrastructural finding. An heritable abnormality in the enzymatic degradation of structural glycosaminoglycans leads to profound disruption of the normal mechanisms of growth and development. PMID- 1907535 TI - Bromovinyldeoxyuridine (BVDU) and trifluorothymidine (TFT) in dendritic corneal ulceration: a double blind controlled study. AB - Fifty patients with corneal dendritic ulceration were randomly entered into a double blind clinical trial comparing BVDU eyedrops with TFT eyedrops. Of those receiving TFT 100% healed in a mean time of 6.7 days, while 92% of those receiving BVDU healed in a mean time of 8.7 days. There was no statistical difference between the two groups in terms of numbers healed, but BVDU was significantly slower in terms of days to heal. After a mean follow-up period of 7.5 months there has been one recurrence in each group. PMID- 1907536 TI - Prediction of maximum exercise tolerance in patients with COPD. AB - Exercise tolerance in patients with COPD is difficult to predict from measurements of lung function. We examined multiple physiologic and psychosocial variables in an attempt to predict exercise performance in a group of patients with COPD enrolled in a clinical trial of pulmonary rehabilitation. A total of 119 patients (FEV1 = 1.41 +/- 0.64 L) were divided randomly into either a study group (group A, n = 58) or validation group (group B, n = 61). Stepwise multiple regression in group A revealed that peak oxygen uptake (peak VO2) was predicted best by the following equation: Peak VO2 (L/min) = (0.0327 x DCO) + (0.0040 x MVV)-(0.0156 x peak-exercise VD/VT) + (0.0259 x resting VE) + 0.848; r = 0.90; SE = 0.233 L/min. This equation was then cross-validated in group B. It demonstrated excellent validity: measured peak VO2 (L/min) = (1.13 x predicted peak VO2) 0.0891; r = 0.90; SE = 0.239 L/min. We conclude that exercise tolerance was predicted reasonably well from measurements of lung function and gas exchange in this group of patients with COPD. However, the variability of the prediction would limit its usefulness in individual patients. PMID- 1907537 TI - Persistence of respiratory abnormalities four years after the onset of toxic oil syndrome. AB - We studied a random sample of 436 subjects with TOS aged 18 to 60 years, to assess the prevalence of respiratory involvement four years after onset of the syndrome. Clinical evaluation together with chest roentgenograms, electrocardiogram and functional respiratory tests were carried out. Respiratory involvement occurred in 390 (89.4 percent) individuals and was the most common abnormality detected, followed by neurological disorders in 289 (66.3 percent), osteoarticular symptoms in 171 (39.2 percent), psychiatric disorders in 96 (22 percent), hepatic involvement in 91 (20.9 percent), and sclerodermatous sequelae in 89 (20.4 percent). Among patients with respiratory involvement, dyspnea and cough were the most common complaints. Decreased VC was observed in 151 (34.6 percent) patients and reduced transfer factor of CO in 95 (21.8 percent) patients. Airway obstruction and alveolar hypoventilation were observed only in nine (2.1 percent) patients. Six (1.4 percent) patients suffered from pulmonary artery hypertension. PMID- 1907538 TI - Intermittent short-term negative pressure ventilation and increased oxygenation in COPD patients with severe hypercapnic respiratory failure. AB - With the aim of testing a method that allows increasing concentrations of oxygen to be administered to patients with severe hypoxemia and hypercapnia while avoiding the risk of increasing respiratory acidosis, we studied 17 male patients with advanced chronic obstructive pulmonary disease (COPD) and severe hypercapnic respiratory failure. During 6 h and on one day only, all patients were given intermittent negative pressure ventilation (INPV) together with oxygenation starting at a concentration of 24 percent and increasing to 30 percent. Using this procedure, it was possible to raise arterial PaO2 to safe levels (from 47.2 +/- 3 mm Hg to 61.5 +/- 6 mm Hg, p less than 0.001) without increasing hypercapnia, and a significant drop in PaCO2 levels (from 74.4 +/- 9 mm Hg to 65.6 +/- 12 mm Hg, p less than 0.005) was even observed. One hour after INPV ended, the mean values of PaO2, PaCO2, oxygen saturation, and pH were also significantly better than prestudy values. We conclude that INPV and oxygen therapy with increasing oxygen flow could constitute an alternative option to intubation and mechanical ventilation in cases of severe hypercapnic respiratory failure due to advanced COPD. PMID- 1907539 TI - [A comparison between glibenclamide and glipizide in the treatment of type II diabetes]. AB - This study enrolled 36 newly-diagnosed patients with NIDDM, who were divided into two groups, the glibenclamide group and the glipizide group. In each group there were 18 cases, and both group were equal in average age and duration, steam bread tolerance test, GHbA1 and 6 hematological targets were made in both groups before and after administration with glibenclamide or glipizide. The results were as follows: (1) The hypoglycemic effect of glibenclamide was slightly great than that of glipizide. (2) VWF decreased significantly after administration with glibenclamide for 4 months. But in glipizide, only the length of thrombosis formation in vitro was greatly shortened. Thus glibenclamide was better than glipizide, in postponing and reducing microangiopathy complication. PMID- 1907540 TI - Cytocidal and filamentous response of Escherichia coli cells exposed to low concentrations of hydrogen peroxide and hydroxyl radical scavengers. AB - The hydroxyl radical scavengers thiourea, ethanol, and dimethyl sulfoxide significantly reduced the killing of Escherichia coli elicited by low concentrations of H2O2 (resulting in mode 1 killing) when treatments with the oxidant and the scavengers were performed in a complete growth medium (K medium) but not in M9 salts. In addition, thiourea efficiently prevented the toxic response to high concentrations of H2O2 (resulting in mode 2 killing) under both exposure conditions. Sod A cells, which do not respond with a bimodal pattern of toxicity when challenged with increasing concentrations of H2O2, were markedly protected by thiourea against the lethal action of various levels of the oxidant (which in the wild-type strain result in either mode 1 or mode 2 killing) under conditions of treatments in both K medium and M9 salts. In some experiments, wild type cells were challenged with a low concentration of H2O2 (in the absence or presence of hydroxyl radical scavengers) and then postincubated in fresh K medium for various time intervals. It was found that scavengers were able to inhibit the filamentous response generated by exposure to the oxidant in K medium. Both the length and the number of filaments were markedly reduced. Treatment in M9 salts resulted in a limited number of very short filaments, and this response was slightly reduced by the scavengers. PMID- 1907541 TI - Implications for persistent chlamydial infections of phagocyte-microorganism interplay. AB - In vitro models of Chlamydia trachomatis inhibition by cytokines, human-monocyte derived macrophages (HMDM) and human polymorphonuclear leukocytes (HPMN) are discussed in an attempt to delineate the molecular basis of parasite-host cell interplay in persistent and chronic chlamydial infection. Interferon gamma (IFN) has been found to reversibly inhibit chlamydial growth at an early stage in the replicative cycle, while tumor necrosis factor (TNF) has a more profound effect on chlamydial growth resulting in production of aberrant reticulate bodies and enhancement of production of prostaglandin E2 (PGE2). Chlamydia trachomatis (serovar L2) replicate in HMDM while serovar K has been found to be restricted in these cells. Chlamydiae are killed by HPMN but the cell walls persist undegraded, inducing production of oxygen radicals which can be demonstrated to induce DNA strand scissions in HeLa target cells. Evidence is accumulating that chlamydia specific serum IgA antibodies may serve as a noninvasive serological marker for diagnosis of a number of acute and persistent Chlamydia trachomatis infections. PMID- 1907543 TI - Pharyngeal carriage of Moraxella (Branhamella) catarrhalis in healthy adults. PMID- 1907542 TI - Role of gamma interferon in Toxoplasma gondii infection. AB - Toxoplasma gondii has emerged as an important pathogen in the ever increasing numbers of patients with disorders of the immune system. Better understanding of the mechanisms of resistance of the host against this protozoan is important for development of safe, effective alternative treatment regimens for toxoplasmosis. Gamma interferon is the cytokine that plays a central role in protection against Toxoplasma gondii. The purpose of this review is to highlight the current knowledge of the role of gamma interferon in Toxoplasma gondii infection. PMID- 1907544 TI - In vitro activity of aztreonam, cefotaxime, ceftazidime and imipenem combined with ciprofloxacin against gram-negative bacilli and compared with amikacin combinations against Pseudomonas aeruginosa. PMID- 1907545 TI - A case of Tsutsugamushi disease probably contracted in Africa. PMID- 1907547 TI - Oxidant stress and carcinogenesis. PMID- 1907548 TI - High-dose intravenous glutathione in man. Pharmacokinetics and effects on cyst(e)ine in plasma and urine. AB - Parenteral glutathione has therapeutic potential for targeted delivery of cysteine equivalents. Thus, high doses of reduced glutathione (GSH) protect from the nephrotoxic and urotoxic effects of cisplatinum and oxazaphosphorines. In order to elucidate the underlying mechanisms the kinetics and the effect of glutathione on plasma and urine sulphydryls were studied in 10 healthy volunteers. Following the intravenous infusion of 2 g m-2 of glutathione the concentration of total glutathione in plasma increased from 17.5 +/- 13.4 mumol l 1 (mean +/- SD) to 823 +/- 326 mumol l-1. The volume of distribution of exogenous glutathione was 176 +/- 107 ml kg-1 and the elimination rate constant was 0.063 +/- 0.027 min-1 corresponding to a half-life of 14.1 +/- 9.2 min. Cysteine in plasma increased from 8.9 +/- 3.5 mumol l-1 to 114 +/- 45 mumol l-1 after the infusion. In spite of the increase in cysteine, the plasma concentration of total cyst(e)ine (i.e. cysteine, cystine, and mixed disulphides) decreased, suggesting an increased uptake of cysteine from plasma into cells. Urinary excretion of glutathione and of cyst(e)ine was increased 300-fold and 10-fold, respectively, in the 90 min following the infusion. The present data suggest that the concentration of sulphydryls in the urinary tract and, more importantly, the intracellular availability of cysteine increase markedly following parenteral glutathione. The high intracellular concentration of cysteine may protect against cisplatinum and oxazaphosphorine toxicity either directly or indirectly by supporting the synthesis of glutathione. PMID- 1907546 TI - Fluoroquinolones in the treatment of cystic fibrosis: a critical appraisal. AB - While the appropriate usage of antibiotics in cystic fibrosis patients is still a matter of debate, the introduction of oral antipseudomonal antibiotics such as fluoroquinolones represents an eagerly awaited addition to the therapeutic armamentarium. Ciprofloxacin is the single agent most often studied and used in this population for treatment of pulmonary exacerbations. Altered pharmacokinetics of fluoroquinolones have been described in cystic fibrosis patients as for other drugs, and a higher dosage than usual is recommended. Open clinical trials have shown good efficacy of ciprofloxacin in acute infection. A few comparative trials have demonstrated that ciprofloxacin is as effective clinically as conventional intravenous agents. As with other agents, a lack of correlation between clinical improvement and bacteriologic evaluation has been observed. Ciprofloxacin (and possibly ofloxacin) are considered useful alternatives to parenteral agents in therapy of cystic fibrosis patients older than 18 years of age with exacerbations of pulmonary infection. Intermittent therapy with ciprofloxacin alternating with other conventional treatment appears to be a rational approach; clinical trials evaluating the alternation of fluoroquinolones with intravenous anti-pseudomonal therapy are necessary. Considering the potential for emergence of resistance and the not completely elucidated implication of increasing MICs during ciprofloxacin therapy, the duration of treatment should be limited to 2 to 4 weeks. In older children (12 to 18 years old), ciprofloxacin provides an alternative to intravenous agents when clinically justifiable. In view of the possibility of fluoroquinolone associated arthropathy in younger children, ciprofloxacin should be used judiciously when no alternative agents are available or in life-threatening situations. PMID- 1907549 TI - Are leucocyte-derived free radicals involved in ischaemia in human legs? AB - Leucocyte-derived free radicals were monitored in 30 stage II peripheral vascular disease (PVD) patients in an open placebo-controlled study. Linked to a transcutaneous oxygen pressure (TcPO2) monitor, they performed two consecutive standard treadmill tests (5 min, 2 km h-1, 12% slope) before and after 15-days treatment with placebo or a leucocyte-derived free radical scavenger (Piroxicam, 20 mg day-1), the second test being carried out at the TcPO2 half-recovery time. Blood samples were collected at baseline, at the maximum walking times and the TcPO2 half recovery times. The total and differential leucocyte counts, the percentage of cells with pseudopodia or cytoplasmatic irregularities, the filterability rates (using a positive pressure Nuclepore filter system) of the main leucocyte subfractions and plasma oxidant activity were monitored. Compared with values before treatment and with the placebo-treated group Piroxicam therapy significantly (P less than 0.001) reduced the final half-recovery time, the percentage of cells with pseudopodia and the level of plasma oxidant activity (P less than 0.01) and kept the granulocyte filterability rate stable, showing leucocyte-derived free radicals are involved in peripheral ischaemia. PMID- 1907550 TI - Peripheral and hepatic insulin sensitivity in healthy elderly human subjects. AB - Insulin resistance has been reported in normal ageing but discrepancies between such studies may be related to compounding factors such as body composition and exercise patterns. We employed a two-step hyperinsulinaemic euglycaemic clamp to assess peripheral and hepatic tissue insulin sensitivity and glucose recycling in 13 elderly (E) and 14 young (Y) healthy subjects controlling for the above factors. There was no difference in basal hepatic glucose production (E: 2.36 +/- 0.06, Y: 2.47 +/- 0.1 mg kg-1 min-1; P = 0.4). At step 1 (insulin infusion 15 mU kg-1 h-1) glucose turnover was similar (E: 2.65 +/- 0.13, Y: 2.88 +/- 0.22 mg kg 1 min-1; P = 0.4) but hepatic glucose production was lower in the elderly group (0.20 +/- 0.16 vs 0.64 +/- 0.10 mg kg-1 min-1; P = 0.03). At step 2 (insulin infusion 50 mU kg-1 h-1) glucose turnover was similar (E: 7.60 +/- 0.24, Y: 8.05 +/- 0.34 mg kg-1 min-1; P = 0.3) and hepatic glucose production was equal but negative (E: -1.35 +/- 0.18, Y: -1.34 +/- 0.22 mg kg-1 min-1; P = 0.9). Glucose recycling did not differ between the groups at any stage. Similar serum insulin levels were achieved in both groups at each step. Decreased glucose tolerance was confirmed in E with a higher 2 h blood glucose after an OGTT (5.3 +/- 0.4 vs 4.1 +/- 0.3 mmol l-1; P = 0.03) but incremental insulin response was similar (E: 3236 +/- 289, Y: 3586 +/- 463 mU l-1 min-1; P = 0.5). We conclude that changes in hepatic tissue insulin sensitivity do not cause the deterioration in glucose tolerance observed with age. A small reduction in both peripheral tissue insulin sensitivity and late insulin secretion may be responsible. PMID- 1907551 TI - Plasma volume changes during hypoglycaemia: the effect of autonomic blockade. AB - To investigate the role of the autonomic nervous system in changes in blood volume and composition induced by acute hypoglycaemia in man, seven healthy subjects participated in three experiments on separate days: insulin-induced hypoglycaemia with concomitant alpha-adrenoceptor blockade; insulin-induced hypoglycaemia with total autonomic blockade (alpha-adrenoceptor blockade combined with beta-adrenoceptor blockade and atropine); and insulin-induced hypoglycaemia without any autonomic blockade. In the experiments without autonomic blockade the peripheral venous hematocrit increased, plasma volume decreased, intravascular albumin content decreased and the transcapillary escape rate of albumin increased. In both experiments with autonomic blockade the increase in venous haematocrit was abolished, yet plasma volume decreased, intravascular albumin content decreased and the transcapillary escape rate of albumin increased in these experiments. Thus, the changes in plasma volume and composition in response to hypoglycaemia are due to the combined actions of adrenaline and of insulin. PMID- 1907552 TI - Thermogenic responses to noradrenaline are unaltered following energy supplementation in chronically energy-deficient human subjects. AB - A group of chronically undernourished labourers underwent a period of controlled supplementary feeding (3.35 MJ per day) over a period of 12 weeks. Thermogenic responses to Noradrenaline (NA) (0.15 microgram kg-1 fat-free mass per min) were assessed (1) before supplementation (2) during the 12th week of supplementation and (3) 12-16 weeks following the cessation of supplementation. There were significant changes in anthropometric indices and basal metabolic rates (BMR) during the three stages of the study; however, these were not accompanied by significant changes in the thermogenic responses to NA. PMID- 1907553 TI - Spinal and forearm bone mass in relation to ageing and menopause in healthy Italian women. AB - Most studies concerning bone status have been performed in Nordic and Anglo-Saxon countries and few data are available on southern European populations. We performed a cross-sectional study on spine and forearm bone mass in 234 healthy Italian women and related the results to age and time since menopause. Forearm bone mass does not decline in premenopausal age, whereas, as far as the spine is concerned, a significant reduction appears 3 years before the mean age of menopause; in both cases, the occurrence of menopause accounted for an accelerated phase of bone loss. In postmenopausal women both spine and forearm bone mass show a stronger correlation with years since menopause than with age. According to a linear exponential model, the rate of spinal bone loss per year since menopause is around 4% in the first 3 years which slows down to around 2% in the 5th year; the corresponding rates of forearm bone loss are 2% and 1.3%, respectively. PMID- 1907554 TI - Effect of human recombinant erythropoietin on anaemia and dialysis efficiency in patients undergoing continuous ambulatory peritoneal dialysis. AB - The effect of long-term treatment with human recombinant erythropoietin (rHuEPO) has been studied in nine end-stage renal disease patients on continuous ambulatory peritoneal dialysis (CAPD). RHuEPO was administered subcutaneously twice weekly in rising doses starting with 50 Ukg-1 body weight. After 3 months of rHuEPO haemoglobin increased from 77.7 +/- 3.2 to 112.7 +/- 5.6 g l-1 (P less than 0.03), haematocrit rose from 22.8 +/- 1.2 to 30.3 +/- 1.7% (P less than 0.01). A consistent decrease in ferritin concentration was observed during this time (P less than 0.05). After 12 months of rHuEPO treatment and increased oral iron supplementation the rises of haemoglobin and haematocrit remained stable without other significant haematological changes. The rHuEPO-induced rise in haematocrit was associated with an increased peritoneal ultrafiltration (UF) without change in diuresis and body weight. UF improved from 128 +/- 28 ml 4 h-1 dwell time to 273 +/- 45 ml 4 h-1 (P less than 0.03) within 3 months of rHuEPO treatment, and remained stable during the following study period (month 12: 253 +/- 43 ml 4 h-1, P less than 0.05). The rise in UF resulted in improved peritoneal clearances of creatinine, urea, potassium, and phosphate (P less than 0.05, month 3). No change was observed in serum urea, creatinine, calcium, and potassium. Serum phosphate increased throughout the first 6 months of rHuEPO (P less than 0.05). No severe adverse effects of rHuEPO treatment could be observed. The present results demonstrate that long-term subcutaneous administration of rHuEPO is effective in correcting renal anaemia in CAPD patients and may improve dialysis efficiency by increased peritoneal ultrafiltration. PMID- 1907555 TI - Suppression of proliferation of human epidermal keratinocytes by 1,25 dihydroxyvitamin D3. Analysis of its effect on psoriatic lesion and of its mechanism using human keratinocytes in culture. AB - Psoriasis is a genetically determined chronic disease of the skin, and an accelerated proliferation of epidermal keratinocytes is one of the pathophysiological characteristics of psoriatic lesion. Recently, it was reported that topical administration of 1,25-dihydroxyvitamin D3 was effective for psoriasis. Our study was done to investigate the effect of 1,25-(OH)2-D3 on cell kinetics on human epidermal keratinocytes as a possible mechanism of its effect on psoriasis. After 24-h application of 1 microgram g-1 1,25-(OH)2-D3 ointment to psoriatic lesion, the number of mitotic keratinocytes decreased. When the cultured human keratinocytes were exposed to 10(-8) mol l-1 1,25-(OH)2-D3 for more than 9 days, inhibition of cell proliferation was noted. DNA distribution analysis by flow cytometry showed a decrease in cells in the S phase, and increase in 2c cells. This indicates blockade of the cell cycle in the G1 phase. The cell cycle time was not extended as a result of 1,25-(OH)2-D3-treatment. PMID- 1907556 TI - Thyroid function tests in patients with acquired immune deficiency syndrome and healthy HIV1-positive out-patients. AB - The thyroid function tests as well as evidence of thyroiditis were studied in 18 male patients with acquired immune deficiency syndrome (AIDS) and 12 healthy HIV1 positive persons compared with an age-matched control group. Serum total thyroxine was not significantly different between the groups, but both serum total triiodothyronine, triiodothyronine uptake test, and free thyroid hormone indices showed significantly decreasing values from HIV1-positive healthy persons to AIDS patients compared with controls (P value from less than 0.05 to less 0.001). Serum TBG was elevated in HIV1-positive subjects and in patients with AIDS, with a significant inverse correlation with the T3-uptake test (Spearman's rho = 0.657, P less than 0.01). There was no correlation between thyroxine binding globulin and the other measured variables. The serum level of thyrotropine was not significantly different in the groups, whereas serum thyroglobulin was significantly lowered in the AIDS group. There was no correlation between thyroid function variables and survival time, hepatic function and ratio of T-helper to T-suppressor cells. No evidence of thyroiditis was observed. In conclusion thyroid tests showed an atypical outcome in HIV1 positive patients with or without AIDS compared with the pattern normally seen in non-thyroid illness, and should, therefore, caution the interpretation of the biochemical changes when diagnosing abnormal thyroid function in these patients. PMID- 1907557 TI - Increased insulin-stimulated glucose uptake by exercised human muscles one day after prolonged physical exercise. AB - We evaluated whether the increased peripheral insulin sensitivity often reported after physical exercise is generalized or limited to the active musculature. Substrate exchange in leg (previously active) and forearm (previously inactive) were measured by catheterization technique basally and during a hyperinsulinaemic euglycaemic clamp (2 mU insulin kg-1 BW min-1) in nine healthy men before and 1 day after 3-h exercise (50% VO2max). One day after exercise basal glucose uptake was unchanged in the leg, while it was decreased in the forearm (-61%, P less than 0.01) compared with the pre-exercise condition. Glucose uptake during hyperinsulinaemia was increased in the leg (+31%, P less than 0.05), but not in the forearm. Basal lactate release by the leg was increased by the exercise, while lactate release by the forearm was decreased, significantly only during the clamp. These results indicate that local and not systemic factors are responsible for the changes in insulin sensitivity observed in the recovery from physical exercise. PMID- 1907558 TI - Doppler echocardiographic analysis of cardiac flow during the Mueller manoeuver. AB - The inspiration against a closed airway, the Mueller manoeuver, leads to a negative intrathoracic pressure. It is controversially discussed whether this is causing an augmentation of right heart murmurs. There is only limited knowledge on the temporal relationship of the negative intrathoracic pressure with right and left ventricular filling and stroke volume. To investigate this relationship, the flow through the mitral, aortic, tricuspid and pulmonary valves was studied continuously by Doppler echocardiography during a standardized Mueller manoeuver in 15 healthy subjects (age 45 +/- 10 years). Five heart beats after the initiation of the manoeuver, flow through the mitral and aortic valve decreased 12.2 +/- 7.2% (P less than 0.001) and 10.1 +/- 6.6% (P less than 0.001), respectively. A transient increase of 15.1 +/- 9.2% (P less than 0.001) in tricuspid flow was followed by a 14.3 +/- 9.8% (P less than 0.005) increase of flow through the pulmonary artery. Ten heart beats after the initiation of the Mueller manoeuver, flow through the pulmonary artery again reached baseline, while tricuspid flow remained below baseline values. In contrast to previous studies, our results indicate that the Mueller manoeuver causes a small and transient increase in right ventricular stroke volume which is unlikely to cause a marked augmentation in right heart murmurs. PMID- 1907559 TI - The influence of gestational age on bilirubin conjugation in newborns. AB - Unconjugated, mono- and diconjugated bilirubin levels were determined in serum soon after birth, and followed up for several days. Fourteen preterm neonates were studied with a gestational age below 33 weeks (n = 7) or between 34 and 37 weeks (n = 7), respectively, as well as 19 full-term newborns either untreated (n = 9) or treated by phototherapy (n = 10). Bilirubin and its derivatives were analysed by alkaline methanolysis and spectrometry after separation by thin-layer chromatography. In normal full-term neonates total and unconjugated bilirubin reached peak levels at days 2-4. Thereafter, a decline of 11% per day was detectable. Monoconjugates in serum amounted to 3.1 +/- 1.1% of total pigment and remained at that level. The relative amount of diconjugates increased from 0.55 +/- 0.25% (2-4th postnatal day) to 1.62 +/- 0.99% (9-13th day of life). The rapid decline of unconjugated bilirubin paralleled by an increase of diconjugates are an expression of the maturation process for bilirubin conjugation. The premature neonates with less than 33 weeks gestation exhibited an increase of unconjugated serum bilirubin up to the 4-5th postnatal day, the decline thereafter amounted 2% per day. The fraction of 2.3 +/- 1.1% monoconjugates was small and exhibited only a moderate increase in the follow up. In contrast diconjugates were undetectable or very low and remained at this level. These results suggest the presence of a more severe immaturity as well as a slower maturation process of bilirubin conjugation in preterm newborns.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1907560 TI - Hyperaluminaemia in critically ill patients: role of antacid therapy and impaired renal function. AB - A significant rise in serum concentrations of aluminum was demonstrated in 23 patients prophylactically treated with the antacid magaldrate, whereas no increase in serum aluminium was observed in another 26 critically ill patients, in whom the use of antacids was avoided. In parallel, urinary excretion rates of aluminum rose to values close to maximum 72 h after antacid therapy had been started. Hyperaluminaemia was most marked in patients with acute renal failure undergoing continuous haemofiltration, but a significant increment in serum aluminium was also noted in patients with impaired renal function in the predialytic state. In the latter group and in patients with normal renal function there was a significant negative correlation between urinary excretion rates of aluminium and creatinine clearance after 48 h of treatment suggesting an enhancement of gastrointestinal absorption of aluminium in the presence of chronic renal failure. Maximum serum concentrations of aluminium did attain critical values in some patients with acute renal failure, but no overt signs of aluminium toxicity were noted. However, in light of both, possible subtle toxicity and enhanced absorption of aluminium in critically ill patients with renal failure, the prophylactic use of antacids in this setting should be re evaluated cautiously. PMID- 1907561 TI - Role of thyrotropin-releasing hormone in acid secretory response induced by lowering of body temperature in the rat. AB - Acid secretory and mucosal ulcerogenic responses to hypothermia (36-24 degrees C) were examined in anesthetized rats, and the role of thyrotropin-releasing hormone (TRH) in these responses was investigated. Lowering of body temperature (less than 32 degrees C) induced acid hypersecretion and damage in the gastric mucosa. These responses reached a maximum at a body temperature of 28 degrees C and were completely abolished by bilateral cervical vagotomy and significantly inhibited by intracerebroventricular (i.c.v.) administration of TRH antiserum (10 microliters/rat). TRH (10 micrograms/rat) given i.c.v. to the normothermia rat, caused an increase of acid secretion with a pattern similar to those observed during hypothermia. The blood levels of thyroid-stimulating hormone rose significantly during exposure of cold, and this response preceded the onset of acid hypersecretion and lesion formation. Thus, lowering of body temperature induces vagal-dependent gastric acid secretion, probably mediated by TRH released in response to cold exposure, and may be an important element in the etiology of stress ulceration. PMID- 1907562 TI - Improved coronary thrombolysis by tissue-type plasminogen activator in the presence of BAY U 3405. AB - The effect of BAY U 3405 (3 mg/kg i.v.) was tested on recombinant tissue-type plasminogen activator (rt-PA)-induced thrombolysis of an experimentally induced coronary thrombosis in anaesthetized dogs. BAY U 3405, given immediately before an rt-PA infusion, reduced time to reperfusion by more than 50% compared with vehicle-treated controls (P less than 0.01). After cessation of the rt-PA infusion, BAY U 3405 reduced the reocclusion rate compared to controls (P less than 0.05). These results show that BAY U 3405 improves rt-PA-induced coronary thrombolysis in a canine model. PMID- 1907563 TI - Inhibition of prolactin secretion by endothelin-3 is pertussis toxin-sensitive. AB - The effect of pertussis toxin (PTX) pretreatment on endothelin-3 (ET-3)-mediated inhibition of prolactin secretion from primary cultures of rat anterior pituitary cells was examined. Monolayer cultures of anterior pituitary cells were treated with either 20 ng/ml PTX dissolved in media or with media alone (control) on the third day of culture. Exactly 24 h after PTX pretreatment, cells were challenged with either 100 nM ET-3 dissolved in media or media alone (control) for 4 or 48 h. ET-3 significantly (P less than 0.01) inhibited prolactin secretion in both the 4 and 48 h incubations. However, if the cells had been previously treated with PTX, ET-3 did not significantly affect prolactin secretion. These data suggest that a PTX-sensitive G protein mediates ET-3-induced inhibition of prolactin secretion and that ET-3 may invoke a signal transduction mechanism in the lactotroph which is distinct from those described in other cell types. PMID- 1907564 TI - Effects of hypophysectomy on pro-thyrotropin-releasing hormone concentrations in rats. AB - The effects of hypophysectomy on pro-thyrotropin-releasing hormone (pro-TRH) and TRH concentrations in the rat hypothalamus, cerebrum, cerebellum and brain stem, stomach and eye were studied. The hypophysectomy was performed via ear route and the rats were used for experiments at seven days after the operation. The hypophysectomized rats were administered T4 (500 micrograms/kg), T3 (100 micrograms/kg), TRH (1.0 mg/kg), or bovine TSH (1.25 IU/kg) was injected ip, and five rats in each subgroup were decapitated at four hours after the injection. Pro-TRH, TRH, TSH and thyroid hormone were measured by their radioimmunoassays. Immunoreactive pro-TRH (ir-pro-TRH) concentrations in the hypothalamus increased significantly after hypophysectomy, while its concentrations in the other tissues showed no changes. The immunoreactive TRH (ir-TRH) concentrations in the hypothalamus decreased significantly after hypophysectomy, but its concentrations did not change in the other tissues. In the hypophysectomized rats, ir-pro-TRH concentrations in the hypothalamus decreased significantly after T4 or T3 injection and tended to decrease after TRH or TSH injection. The ir-TRH concentrations in the hypothalamus increased significantly after T4, T3, TSH or TRH injection in the hypophysectomized rats. However, ir-pro-TRH and ir-TRH concentrations in the other tissues did not change after these hormone injections. The findings suggest that hypophysectomy stimulates TRH synthesis and release in the hypothalamus, and that pro-TRH synthesis in the tissues except the hypothalamus may not be regulated with thyroid hormone. PMID- 1907566 TI - Two years treatment with almitrine bismesylate in patients with hypoxic chronic obstructive airways disease. AB - Eighty nine patients with hypoxic chronic obstructive airways disease (COAD) were enrolled into the 1 year Vectarion International Multicentre Study-VIMS in 4 centres, Sheffield (UK), and Antwerp, Liege and Namur (Belgium). At the end of the year the remainder were invited to continue taking placebo or almitrine bismesylate (100-200 mg daily) in the same double blind manner for a further 12 months. In the almitrine treated patients mean arterial oxygen tension (Pao2) at the end of the treatment period improved from 7.5 (0.5) kPa to 8.2 (1.3) kPa (p less than 0.01) and arterial carbon dioxide tension (Paco2) fell from 6.1 (0.8) kPa to 5.8 (0.9) kPa (p less than 0.01). Forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and measurements of breathlessness were unchanged. In the placebo treated group changes in the above variables were not significant. Twenty nine patients withdrew from the almitrine group with seven deaths and six cases of peripheral neuropathy, and 22 patients withdrew from the placebo group with six deaths and two cases of peripheral neuropathy. Death rates between the groups were not significantly different. In conclusion, 2 yrs of almitrine treatment (100-200 mg daily) leads to a persistent slight improvement in PaO2 and PaCO2 but no benefit in survival was demonstrated. Patients in this study had a high incidence of drug related side-effects. Lower dose schedules should be investigated. PMID- 1907565 TI - Effect of chronic clonidine administration on GH secretion in adult human subjects. AB - It is well known that the acute administration of clonidine, an alpha 2 adrenergic agonist commonly used as an antihypertensive drug, stimulates GH secretion, likely via hypothalamic growth hormone releasing hormone (GHRH) release. Conversely, evidences of a hyperactivity of GHRH-GH-somatomedin C (SMC) axis during chronical administration of clonidine are controversial. In this study, GH and SMC levels have been evaluated in 16 hypertensive patients chronically treated with clonidine. The subjects were randomized to receive either TRH or saline with the aim of evaluating the non specific GH response to TRH as compared to spontaneous fluctuations during a control test. In basal conditions, GH and SMC concentrations in clonidine treated patients were similar to those observed in an age and sex matched group of normal untreated subjects. An abnormal increase in plasma GH occurred in 5 out of the 10 patients who received TRH, while plasma GH did not show significant variations during testing in the subjects who received saline. It is suggested that chronical administration of clonidine does not induce an hyperactivity of GHRH-GH-SMC axis as estimated by plasma GH and SMC concentrations, but may induce a disorder in hypothalamic control of GH secretion, possibly implicated in the abnormal GH responsivity to TRH. PMID- 1907567 TI - Inverse regulation of glucose transporter Glut4 and G-protein Gs mRNA expression in cardiac myocytes from insulin resistant rats. AB - The present study examined the mRNA levels of glucose transporter Glut4 and G protein Gs alpha-subunit in isolated ventricular myocytes from lean and genetically obese (fa/fa) Zucker rats and streptozotocin-diabetic rats. In obese animals the amount of transcripts coding for Glut4 increased to 122 +/- 6% of lean controls, whereas the mRNA coding for Gs alpha-subunit decreased by 42 +/- 12%. An unaltered level of Gs mRNA was observed in insulin deficient rats. When cardiomyocytes from normal rats were treated with insulin, the Glut4 transcript level increased by 48 +/- 5%, whereas the Gs mRNA level decreased by 55 +/- 8%. The findings suggest that insulin may act as a potential regulator of Glut4 and Gs mRNA expression in the cardiac cell. PMID- 1907568 TI - Presence of an acyl carrier protein in NADH:ubiquinone oxidoreductase from bovine heart mitochondria. AB - The amino-acid sequence of a subunit of NADH:ubiquinone oxidoreductase from bovine heart mitochondria has been determined and is closely related to those of acyl carrier proteins that are involved in fatty acid biosynthesis in Escherichia coli and plants. Evidence for the presence of covalently attached pantetheine-4' phosphate in the bovine protein has been obtained by determination of the molecular mass of the isolated subunit by electrospray mass spectrometry, before and after incubation of the protein at alkaline pH under reducing conditions. This decreased the molecular mass from 10,751.6 to 10,449.4, a difference of 302.2 mass units; the value calculated from the protein sequence with one covalently attached pantetheine-4'-phosphate is 10,449.8. The acyl group which is removed by alkaline reduction, appears to be attached via a thioester linkage. By analogy with the bacterial protein it is likely that the attachment site of the pantetheine-4-phosphate is serine-44, which is found in a highly conserved region of the sequence. At present the function of the acyl carrier protein in mitochondrial complex I is not understood. PMID- 1907569 TI - Cyanobacteria contain a mitochondrial complex I-homologous NADH-dehydrogenase. AB - Thylakoid and cytoplasmic membranes of the cyanobacterium Synechocystis sp. PCC 6803 were purified by sucrose gradient centrifugation. Both membranes oxidize NADH in a rotenone-sensitive reaction. Antibodies prepared against psbG/ndhK and ndhJ fusion proteins detect the corresponding polypeptides in both membrane preparations. This demonstrates that a NADH-dehydrogenase, homologous to the mitochondrial NADH-ubiquinone-oxidoreductase (complex I of the respiratory chain) is present in cyanobacteria. The NADH-dehydrogenase can be solubilized with the detergent beta-D-dodecylmaltoside. Sedimentation analysis of the solubilized enzyme on a sucrose gradient indicates that it is a multisubunit protein complex. PMID- 1907570 TI - Determination of the branch location of extra N-acetyllactosamine units in sialo N-linked tetraantennary oligosaccharides. AB - An approach is presented for the determination of the branch location of 1 or 2 extra N-acetyllactosamine units in sialo N-linked carbohydrate chains from glycoproteins. Tetraantennary oligosaccharides containing extra N acetyllactosamine units were digested with endo-beta-galactosidase, followed by treatment with N-acetyl-beta-glucosaminidase, yielding products which could be analysed by 1H-NMR spectroscopy, thereby giving conclusive data about the location of the extra units in the intact structures. PMID- 1907571 TI - Molecular basis for different rates of recovery from inactivation in the Shaker potassium channel family. AB - The two alternative carboxyl-termini of Shaker K+ channels strongly influence the rates of inactivation and of recovery from channel inactivation. We show that this distinct inactivation behaviour is due to an alanine/valine amino acid replacement within the Shaker carboxyl-terminus at a site that occurs within the proposed membrane spanning segment S6. PMID- 1907572 TI - The limited applicability of thrombolysis. PMID- 1907573 TI - Thrombolysis in critical ischaemia. PMID- 1907574 TI - [Bonding of fragments in coronal fractures]. AB - The coronal fractures of the upper incisors for traumatic injuries represent the 8% of the total dental trauma. The use of new dentinal adhesive have permitted to obtain new interesting development in dental traumatology and dental aesthetic, like the possibility of the utilization of the dental fragment, of the incisor broken for a trauma. The new dentinal adhesive is the Gluma (Bayer). The Author describes the technique, the times, some particulars and step by step all the method to obtain good final results. The Author described complicated and uncomplicated crown fractures, fractures with several fragments and corono radicular fractures with reattachment of the fragment. The long distances results (3 years) of 48 cases are presented. Finally are presented all the advantages compared to the traditional methods with the composites materials. PMID- 1907575 TI - [Dental tissue-composite bonding. SEM study]. AB - The Authors investigated the different operative methods effects in the transition zone between human fresh teeth calcified tissues and a composite material. Morphological observations, done by means of standard and back scattered scanning electron microscopy, demonstrated the Gluma adhesion system efficiency towards enamel and dentin if manufacturing's applying systems are carefully followed, by showing a structure with no solutions of continuity between tooth and restoration. PMID- 1907576 TI - Biochemical characterisation of mitochondrial and lysosomal particles in foetal and neonatal rats. AB - 1. The sedimentation coefficients of the mitochondria are larger in the foetal as compared to the adult rats. For cytochrome oxidase, the values are respectively 18.700 x 10(3) and 13,550 x 10(3) S. 2. Lysosomal sedimentation coefficients are smaller in the foetal as compared to the adults. For beta galactosidase, the values are respectively 5.090 x 10(3) and 10.430 x 10(3) S. 3. It is concluded that the mitochondria are larger and the lysosomes smaller in size in the foetus as compared to the adults. 4. The external membrane of neonatal mitochondria and the membrane of foetal and neonatal lysosomes are more resistant to osmotic swelling. PMID- 1907577 TI - Molecular cloning of human beta 1,4-galactosyltransferase and expression of catalytic activity of the fusion protein in Escherichia coli. AB - 1. Three groups of cDNA clones (total of six) for human UDP-galactose: beta N acetylglucosamine galactosyltransferase (4 beta GT) were obtained by screening of a fetal liver library in lambda gt11 with an affinity purified anti4 beta GT antibody. 2. One group of clones (three clones) reacted with two distinct anti4 beta GT murine monoclonal antibodies. 3. Nucleotide sequence of this group of clones were similar to published sequence for human 4 beta GTcDNA, except the 74 nucleotides at the 5'-end. 4. Partially purified fusion protein encoded by this group of clones showed all the catalytic properties of 4 beta GT, although the cDNA was partial and the protein was probably unglycosylated. PMID- 1907578 TI - Inhibition of thymidylate synthase by glyceraldehyde 3-phosphate. AB - 1. A number of common metabolites which had carbonyl and/or phosphate groups were tested for their ability to alter the activity of thymidylate synthase from Lactobacillus casei. Glyceraldehyde 3-phosphate was found to be an effective inhibitor of thymidylate synthase. 2. Glyceraldehyde 3-phosphate reversibly inhibited thymidylate synthase with a K1 of 12-13 microM; the inhibition was competitive with dUMP and noncompetitive with 5,10-methylenetetrahydrofolate which is consistent with an ordered addition of substrates. PMID- 1907579 TI - Calmodulin- and Ca2(+)-insensitive fatty acid methyltransferase from RINm5F cells. Inhibition by trifluoperazine and W7. AB - 1. Methylation of endogenous lipids by homogenates of rat insulinoma cells was studied. 2. 3H-methyl groups (38 pmol/mg protein per 10 min) from [3H-methyl]S adenosyl-L-methionine were incorporated into endogenous lipids, mainly (greater than 80%) into the neutral lipid fraction. 3. The reaction was sensitive to heat, was almost abolished by S-adenosyl-L-homocysteine, but insensitive to the addition of EGTA (5 mM), Ca2+ (5-100 microM) and/or calmodulin (15 microns). 4. At concentrations relevant for calmodulin antagonistic activity strong inhibition by W7 and trifluoperazine (25-100 microM each), but not by CGS 9343B (10 microM), was observed. 5. Calmodulin antagonists of phenothiazine- and sulfonamide-type appear to block the fatty acid methyltransferase in a way unrelated to calmodulin. PMID- 1907580 TI - Developmentally regulated alternative splicing of Drosophila myosin heavy chain transcripts: in vivo analysis of an unusual 3' splice site. AB - The 3' penultimate exon (exon 18) of transcripts from the muscle myosin heavy chain (MHC) gene of Drosophila melanogaster is excluded from mRNAs of embryonic and larval muscle, while it is included in mRNAs of adult thoracic muscles. By transforming organisms with the MHC gene 5' end, linked in-frame to the MHC gene 3' end, we were able to generate correct tissue-specific expression of this minigene and stage-specific splicing of exon 18, indicating that all the cis acting sequences necessary for alternative splicing are contained within the construct. The 3' splice site that precedes exon 18 is unusually purine-rich, may form a stem-loop structure with the 5' splice site following exon 18, and is conserved relative to the splice site of an alternative exon of the Drosophila alkali myosin light chain gene. We converted the MHC gene 3' splice junction to a consensus splice site and also inserted the branchpoint and 3' splice site of a constitutively spliced intron in its place. These alterations had no effect on the splicing pathway in vivo, ruling out the possibility that the unusual splice junction, or secondary structures that involve this splice junction, directly regulate alternative splicing of exon 18. PMID- 1907581 TI - Glycoproteins from Bufo arenarum vitelline envelope with fertility-impairing effect on homologous spermatozoa. AB - When spermatozoa from Bufo arenarum are incubated with molecules extracted from the vitelline envelopes of homologous oocytes, they lose their fertilizing capacity. Those molecules are glycoproteins, and the elimination of mannoside residues from them results in activity loss, while digestion of the proteic moiety did not alter their biological effect. Sepharose-concanavalin A columns were used to purify the glycoproteins, since the active fraction binds to the column. The fertility-impairing effect observed does not seem to be mediated by an acrosome reaction-inducing effect. PMID- 1907582 TI - Immunocytochemical and biochemical characterization of guanine nucleotide-binding regulatory proteins in mammalian spermatozoa. AB - Polyclonal antisera directed against conserved and subtype-specific peptide sequences of the alpha-subunits of guanine nucleotide-binding regulatory proteins (G proteins) were used to characterize the nature of mammalian sperm G proteins and to determine whether their localization was consistent with their proposed roles in mediating ZP3-induced acrosomal exocytosis. Mouse and guinea pig sperm exhibit positive immunofluorescence in the acrosomal region using an antiserum directed against a peptide region common to all alpha-subunits of G proteins (G alpha). The immunofluorescence disappears after sperm have undergone the acrosome reaction, suggesting that the immunoreactive material is associated with the plasma membrane/outer acrosomal membrane region overlying the acrosome. The presence of G proteins in this region is confirmed by the presence of a Mr 41,000 substrate for pertussis toxin (PT)-catalyzed [32P]ADP-ribosylation in purified plasma membrane/outer acrosomal membrane hybrid vesicles obtained from acrosome reacted guinea pig sperm. Immunoprecipitation and polyacrylamide gel electrophoresis of PT-catalyzed [32P]ADP-ribosylated protein(s) using anti peptide antisera generated against sequences unique to Gi alpha 1, Gi alpha 2, and Gi alpha 3 confirm the existence of all three Gi subtypes in mouse sperm extracts. Indirect immunofluorescence using an antiserum directed against a peptide region present in Gz alpha, a PT-insensitive G protein, demonstrates positive immunoreactivity in the postacrosomal/lateral face region of the mouse sperm head. This immunoreactivity is retained during acrosomal exocytosis in response to solubilized ZP and then disappears subsequent to this exocytotic event. These data demonstrate that Gi protein alpha-subunits are present in the acrosomal region of mammalian sperm, consistent with their postulated role in regulating ZP3-mediated acrosomal exocytosis, and that PT-insensitive Gz alpha is found in a region of the sperm head distinct from that of the Gi alpha subunits. PMID- 1907583 TI - Organ-specific patterns of gene expression in the reproductive tract of Drosophila are regulated by the sex-determination genes. AB - The sex-determination genes of Drosophila act to repress the developmental pathway for the internal somatic reproductive organs of the opposite sex. By misregulating this pathway during preadult development, the organ-specific expression pattern of the glucose dehydrogenase gene (Gld) in the reproductive tract of adult flies has been changed without a concomitant sexual transformation of the reproductive organs. Misregulation of the tra, tra-2, and dsx genes leads to very similar patterns of ectopic expression of Gld. The induced ectopic patterns of Gld expression at the adult stage occur in a small subset of organs which all normally express the Gld gene during their morphogenesis. These ectopic patterns are irrevocably set during late larval-early pupal development. The normal pattern of Gld expression in several other Drosophila species is quite similar to the ectopic patterns which we have generated in D. melanogaster, suggesting that the interspecific variation in Gld expression may result from variation in the expression of the sex-determination genes. PMID- 1907584 TI - Identification of laminin domains involved in branching morphogenesis: effects of anti-laminin monoclonal antibodies on mouse embryonic lung development. AB - We recently found that polyclonal antibodies to laminin, a basement membrane related glycoprotein, inhibited murine lung morphogenesis when added to organ cultures of mouse embryonic lung. Using a series of monoclonal anti-laminin antibodies with previously characterized subunit specificity (termed AL-1, AL-2, AL-3, AL-4, and AL-5), the deposition and functional involvement of different laminin domains in the developing lung were investigated. By immunohistochemistry the antibodies' reactivity was largely localized to the basement membrane, but was also present diffusely in the extracellular matrix throughout the mesenchyme. Organ cultures of lung explants from Day 12 embryos were cultured for 3 days in the presence of 50-100 micrograms/ml of each antibody or in the presence of the same concentration of immunoglobulins G and M, laminin-neutralized antibody, or medium alone. Cultures were monitored by phase-contrast microscopy, light microscopy, and immunofluorescence. Although all antibodies penetrated the tissues in culture, only two of them inhibited branching activity. These two antibodies were AL-1, which binds on or near the cross region of laminin, and AL 5, which binds to the lateral short arms at the globular end regions of the B chain of laminin. Inhibition of branching with these two antibodies was dose dependent and statistically significant for the two concentrations used. AL-2, AL 3, AL-4, laminin-neutralized antibodies and control immunoglobulins did not alter lung morphogenesis. The two domains of laminin that promote lung branching morphogenesis have been reported by others to promote the attachment of a variety of cells and/or bind heparin. These domains of laminin may promote branching morphogenesis by facilitating cell attachment and, consequently, cell proliferation. PMID- 1907585 TI - Increased intracellular calcium mobilization in platelets from patients with type 2 (non-insulin-dependent) diabetes mellitus. AB - Enhanced platelet functions have been reported in patients with diabetes mellitus. Our recent study demonstrated that phosphoinositide turnover is increased in platelets from diabetic patients. In the present study, we evaluated the abnormality in platelet intracellular calcium mobilization in patients with Type 2 (non-insulin-dependent) diabetes mellitus using fura-2, a fluorescent calcium indicator. Washed platelets were prepared from six diabetic patients with increased platelet aggregation rates (DM-A group), seven diabetic patients with normal platelet aggregation rates (DM-B group), and eight age-matched healthy control subjects. The basal intracellular free calcium concentrations in platelets were similar among the three groups. Thrombin (0.025-0.1 U/ml) induced a dose-dependent increase in intracellular calcium in both the presence and the absence of extracellular calcium. This increase in the presence of extracellular calcium, which depends on calcium influx and release, was significantly higher in the DM-A group than in the DM-B and control groups. However, there was no significant difference between the control group and the DM-B group. In the absence of extracellular calcium, thrombin-induced calcium increase, which depends only on calcium release, was also significantly enhanced in the DM-A group. Furthermore, the calcium increase stimulated by platelet-activating factor (10 nmol/l) with and without extracellular calcium was significantly higher in the DM-A group than in the other groups. Additionally, calcium ionophore A23187 (100 nmol/l) caused a significantly higher calcium increase in the DM-A group with extracellular calcium, while the calcium increase without extracellular calcium showed no significant difference among the three groups. These observations suggest that enhanced intracellular calcium mobilization due to increased calcium influx and release may be closely related to platelet hyperfunctions in diabetes mellitus. PMID- 1907586 TI - Safe and effective tube feeding of bedridden elderly. AB - An increasing number of patients with swallowing disorders due to stroke, head trauma, degenerative neurologic diseases, and other causes are surviving for prolonged periods with tube feeding of commercial formulas as their sole source of nutritional support. Reviewed in this article are the indications, methods, strategies for formula selection, complications, and outcomes of tube feeding in the long-term care patient. PMID- 1907587 TI - Quantification of noncyclooxygenase derived prostanoids as a marker of oxidative stress. AB - Recently, we discovered there is a unique class of prostaglandin F2-like compounds that are formed in vitro from arachidonoyl-containing lipids in plasma by a free radical-catalyzed mechanism. More recent studies have elucidated that these prostanoids are also produced in vivo in humans by a similar noncyclooxygenase mechanism. Levels of these PGF2 compounds detected by a mass spectrometric assay in normal human plasma and urine range from approximately 5 50 pg/mL and 500-3000 pg/mg creatinine, respectively. Circulating levels of the compounds were shown to increase by as much as 200-fold in animal models of free radical-induced lipid peroxidation. These results suggest that quantification of these prostanoids may provide a new approach to assess oxidative stress in vivo in humans. Potential advantages of this approach are that the mass spectrometric assay has a high degree of sensitivity, accuracy, and specificity and the assay can be used to quantitate these compounds in a variety of biological fluids. In addition, quantification of these compounds is of interest because these compounds possess biological activity. Disadvantages of the assay are the potential of ex vivo formation of these compounds in biological fluids containing lipids and, further, these compounds must be differentiated from PGF2 compounds that are formed via the cyclooxygenase enzyme. In addition, because the levels of these compounds in normal human plasma and urine are relatively high, assaying these compounds in circulating plasma and urine may be somewhat insensitive for the detection of increased production at isolated sites of oxidant injury within the body, in which case sampling near localized sites of their formation may be required.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1907588 TI - Failure of recombinant activated factor VII during surgery in a hemophiliac with high-titer factor VIII antibody. AB - Recombinant activated factor VII (rFVIIa) was used before and after inguinal hernioplasty to prevent bleeding in a patient with hemophilia A complicated by a high-potency antifactor VIII inhibitor. rFVIIa (75 micrograms/kg) was given before and after surgery, first by bolus infusions at intervals of 2-3 h for 47 h and then by continuous intravenous infusion at a rate of 38 micrograms/h for an additional period of 12 h. Although no undue bleeding was observed during and for the first 26 h after surgery, the patient subsequently developed wound bleeding and hematomas that necessitated blood transfusion and infusion of porcine factor VIII. This case indicates that rFVIIa is not always successful in patients with antifactor VIII inhibitor and that more experience is needed to establish the optimal doses at surgery. PMID- 1907589 TI - Anticardiolipin antibodies in patients with venous thrombosis. AB - The levels of anticardiolipin antibodies (ACA) and lupus anticoagulant (LAC) were measured in 266 consecutive unselected patients with a history of venous thrombosis. 19 (7.1%) had elevated levels of IgG- or IgM-ACA. The prevalence of LAC was 1 of 266 (0.4%) in the whole patient group and 1 of 19 (5.3%) in the ACA positive group. Patients with elevated ACA levels did not differ from those with normal ACA with regard to age at the first thrombosis, risk of recurrence, presence of arterial thrombosis, and other clinical features. 8 out of 19 (42.1%) patients with elevated ACA levels also had elevated levels of antinuclear antibodies, but only 1 fulfilled the criteria of systemic lupus erythematosus. These data indicate that in some patients with elevated ACA, autoimmune processes may be present. The clinical significance of elevated ACA levels is uncertain. PMID- 1907590 TI - Separation of lupus anticoagulant from anticardiolipin antibodies by ion-exchange and gel filtration chromatography. AB - Separation of lupus anticoagulant from anticardiolipin antibodies in the serum of a patient containing both antibodies is described. A simple two-step procedure utilizing diethylaminoethylcellulose ion-exchange chromatography followed by Sepharose CL-4B gel filtration chromatography allowed the separation of IgM from IgG isotype. Lupus anticoagulant was found to be exclusively IgM, whilst anticardiolipin antibodies were IgG. This is apparently the first report that anticardiolipin antibodies and lupus anticoagulant can be different isotypes and adds to the increasing evidence that they are separate entities. PMID- 1907591 TI - Intra- and postoperative fibrinolysis in patients undergoing cardiopulmonary bypass surgery. AB - The influence of cardiopulmonary bypass (CPB) on fibrinolytic activity was assessed in 100 patients with valvular heart disease or atrial septal defects. Euglobulin fibrinolytic activity (EFA), tissue type plasminogen activator (t-PA) activity, plasminogen activator inhibitor 1 (PAI-1) activity, plasminogen, alpha 2-antiplasmin (alpha 2-AP), fibrinogen degradation products (FDP), and D-dimer were measured pre-, intra-, and postoperatively. There were significant increases in EFA and t-PA activity (p less than 0.002), and decreases in plasminogen and alpha 2-AP (p less than 0.0001) intraoperatively with respect to baseline values. t-PA activity decreased significantly after surgery (p less than 0.002), whereas PAI-1 activity showed a marked increase shortly after operation and on postoperative day 1 (p less than 0.0001). FDP and D-dimer levels were significantly increased both intra- and postoperatively, the latter showing higher values (p less than 0.01 and p less than 0.0001, respectively). This study shows that there is an activation of the fibrinolytic system, as a result of the increased activation of plasminogen and decreased levels of plasmin inhibitors, during CPB surgery followed by a postoperative fibrinolytic shutdown. PMID- 1907592 TI - Increased incidence of euthyroid and hyperthyroid goiters independently of thyrotropin in patients with acromegaly. AB - The incidence of palpable goiters, the thyroid functional state and thyroid radioisotope uptake was analyzed retrospectively in 80 patients with acromegaly and 80 patients with prolactinomas. 71% of all patients with acromegaly had an enlargement of the thyroid (goiter); 49% of them had diffuse and 39% nodular goiters. The incidence of goiters in patients with prolactinomas from the same iodine deficient geographic region was only 35% (82% diffuse and 18% nodular). 17.5% of acromegalic patients underwent thyroid surgery before diagnosis of growth hormone excess. 17.5% of acromegalic patients with goiters had autonomous areas in their thyroids and 5% were clearly hyperthyroid. Goiters developed slightly more often in females (74%) than in males (67%). The mean preoperative growth hormone level was higher in acromegalic patients with goiter. The incidence of goiters was positively correlated with the documented time of elevated growth hormone concentration in serum. Two patients with exaggerated response of thyrotropin (TSH) (delta TSH greater than 20 mU/l) to the application of thyrotropin-releasing hormone (TRH) had no goiters. On the other hand most patients (61%) with goiters had a low TSH-response to TRH (delta TSH less than 10 mU/l) representing in part occult autonomy of thyroid function. No patient with prolactinoma has had previous thyroid surgery nor thyroid autonomy. One patient with prolactinoma suffered from Graves' disease and none of the acromegalic patients had this disease. We finally conclude that the elevation of growth hormone leads to increased incidence of euthyroid and hyperthyroid (autonomous) goiters independently of the influence of TSH. PMID- 1907593 TI - Conversion of inpatient mental health benefits to outpatient benefits. PMID- 1907594 TI - Changes in psychiatric inpatient treatment of children and youth in general hospitals: 1980-1985. AB - Changes in the prevalence of inpatient psychiatric treatment of children and youth in short-term general hospitals between 1980 and 1985 were investigated. During that period, the locus of treatment of mental illness among children and youth shifted dramatically away from specialized facilities to general hospitals without psychiatric units. Among general hospitals without psychiatric units, the number of inpatient psychiatric episodes treated increased dramatically, patients' average length of stay almost doubled, and the total days of care provided more than tripled. The increased care was paid for primarily by Medicaid and commercial insurance. Total days of care for drug and alcohol problems among children and youth in general hospitals decreased substantially. The results suggest that general hospitals may be relying on psychiatric treatment to supplement revenues that were limited by Medicare's prospective payment system, which became effective during the period under study. PMID- 1907595 TI - Intrasellar cavernous angioma in neurofibromatosis. AB - A case of neurofibromatosis complicated by a large intrasellar (pituitary) cavernous angioma is reported. Vascular abnormalities, consisting of smooth muscle cell proliferation in the intima of the intermediate and small arteries, were also observed in branches of the renal and pulmonary arteries. An association between neurofibromatosis and intracranial cavernous angioma is discussed. PMID- 1907596 TI - Detection of human spermatid-specific transcripts in peripheral blood lymphocytes of males and females. AB - We describe the detection of ectopic ("illegitimate") transcripts of the proacrosin and protamine 2 genes, which are specific for human spermatogenesis, in non-cultured peripheral blood lymphocytes. After specifically-primed reverse transcription of total lymphocyte RNA, these rare transcripts can be directly visualised after two rounds of polymerase chain reaction with nested primers. Sequence and restriction analyses of the corresponding fragments have confirmed that transcripts of proacrosin and protamine 2 are present in the lymphocytes not only of males, but also of adult females. PMID- 1907597 TI - Interaction between inhibin and melatonin on secretion of rat pituitary gonadotrophins. AB - In presence of melatonin, the suppression of FSH levels by inhibin is reduced (31%) as compared to inhibin given alone (51%) to adult male rats. Likewise, inhibin decreases the prolactin enhancement following melatonin administration. These experiments demonstrate interaction of inhibin and melatonin on the secretion of pituitary gonadotrophins. PMID- 1907598 TI - Immunological abnormalities in pediatric AIDS. AB - HIV infection of a fetus from an infected mother has severe immunological implications because it destroys still immature immune system. The abnormalities observed are precocious in the infants. When the infection occurs in perinatal period, clinical and immunological manifestations can present themselves at the age of 2-5 years. Two patterns of HIV infection can be distinguished. Humoral immunodeficiency is present in a high proportion of patients and leads to repeated bacterial infections and progression of the disease. Immunoglobulin substitution therapy improves clinical manifestations and can help to avoid viral replication. PMID- 1907599 TI - Economic evaluation of a support program for caregivers of demented elderly. AB - An economic evaluation was undertaken concurrently with a randomized trial comparing a Caregiver Support Program (CSP) with existing conventional community nursing care for those caring for elderly relatives at home. The differences in resource consumption were compared with changes in caregiver quality of life, as measured by the Caregiver Quality of Life Instrument (CQLI). A 20% difference from baseline in the CQLI favored the experimental (CSP) group, although this did not reach conventional levels of statistical significance. A comparison of improvement in quality of life with costs implies an incremental cost per quality adjusted life year gained of Canadian $20,000 for the CSP, which compares favorably with other health care interventions. Further, larger studies are required to confirm this result. PMID- 1907600 TI - Cost comparison of parenteral estrogen and conventional hormonal treatment in patients with prostatic cancer. AB - The present study compares the cost of antitumor therapy and adverse cardiovascular effects during the first year of treatment with oral estrogens, nonoral estrogens, or surgical castration in patients with prostatic cancer. We found a much higher cost for patients treated with orchidectomy and oral estrogens than for patients treated with nonoral estrogens. Twenty-five percent of the patients treated with oral estrogen suffered cardiovascular complications, compared to none of the patients treated by orchidectomy or nonoral estrogens. The initial cost of orchidectomy as compared to nonoral estrogen treatment was shown not be balanced within the expected survival time of patients with advanced prostatic cancer. Furthermore, surgical castration causes psychological trauma to the patient. We recommend parenteral estrogen therapy as a low-cost therapeutic regimen in patients with prostatic cancer. PMID- 1907601 TI - In vitro and in vivo regulation of tumor antigen expression by human recombinant interferons. AB - In vitro treatment with either type I or type II interferon (IFN) can selectively enhance the expression of several tumor antigens, such as the carcinoembryonic antigen (CEA) and the tumor-associated glycoprotein-72 (TAG-72) in different human carcinoma cell lines and result in enhanced level of monoclonal antibody (MAb) binding to the cell surface. In vivo animal studies demonstrated that treatment of athymic mice with a type I interferon [i.e. interferon-alpha (A)] significantly increased the expression of a 90 kDa tumor antigen which improved the targeting of a MAb to the carcinoma xenograft. More recent studies reported that in vitro IFN treatment of human adenocarcinoma cells isolated from human malignant serous effusions selectively increased the expression of TAG-72 and CEA. One can envision that the ability of these cytokines to upregulate the level of expression of human tumor antigens presents an important experimental model in which to study the regulation of markers often correlated with epithelial cell differentiation. In addition, the increase of selective MAb-defined antigens may also be exploited in an adjuvant setting to localize higher amounts of MAbs to the tumor cell surface and, thereby, improve the effectiveness of a MAb for tumor diagnosis and, possibly, therapy. PMID- 1907602 TI - Sleep-induced periodic breathing and apnea: a theoretical study. AB - To elucidate the mechanisms that lead to sleep-disordered breathing, we have developed a mathematical model that allows for dynamic interactions among the chemical control of respiration, changes in sleep-waking state, and changes in upper airway patency. The increase in steady-state arterial PCO2 accompanying sleep is shown to be inversely related to the ventilatory response to CO2. Chemical control of respiration becomes less stable during the light stage of sleep, despite a reduction in chemoresponsiveness, due to a concomitant increase in "plant gain" (i.e., responsiveness of blood gases to ventilatory changes). The withdrawal of the "wakefulness drive" during sleep onset represents a strong perturbation to respiratory control: higher magnitudes and rates of withdrawal of this drive favor instability. These results may account for the higher incidence of periodic breathing observed during light sleep and sleep onset. Periodic ventilation can also result from repetitive alternations between sleep onset and arousal. The potential for instability is further compounded if the possibility of upper airway occlusion is also included. In systems with high controller gains, instability is mediated primarily through chemoreflex overcompensation. However, in systems with depressed chemoresponsiveness, rapid sleep onset and large blood gas fluctuations trigger repetitive episodes of arousal and hyperpnea alternating with apneas that may or may not be obstructive. Between these extremes, more complex patterns can arise from the interaction between chemoreflex-mediated oscillations of shorter-cycle-duration (approximately 36 s) and longer-wavelength (approximately 60-80 s) state-driven oscillations. PMID- 1907603 TI - Inspiratory muscle relaxation rate after voluntary maximal isocapnic ventilation in humans. AB - We have investigated whether the capacity of the inspiratory muscles to generate pressure and flow during a ventilatory load is related to changes in inspiratory muscle relaxation rate. Five highly motivated normal subjects performed voluntary maximal isocapnic ventilation (MIV) for 2 min. Minute ventilation and esophageal, gastric, and transdiaphragmatic pressures were measured breath by breath. We observed that ventilation, peak inspiratory and expiratory pressures, and inspiratory flow rate declined from the start of the run to reach a plateau at 60 s that was sustained for the remainder of the exercise. In a subsequent series of studies, MIV was performed for variable durations between 15 and 120 s. The normalized maximum relaxation rate of unoccluded inspiratory sniffs (sniff MRR, %pressure loss/10 ms) was determined immediately on stopping MIV. Sniff MRR slowed as the duration of MIV increased and paralleled the decline in inspiratory pressure and ventilation observed during the 2-min exercise. No further slowing in MRR occurred when ventilation became sustainable. We conclude that, during MIV, the progressive loss of ventilation and capacity to generate pressure is associated with the early onset and progression of a peripheral fatiguing process within the inspiratory muscles. PMID- 1907604 TI - High-frequency ventilation in dogs with three gases of different densities. AB - Dogs were ventilated with a high-frequency oscillation device varying the frequency (5-15 Hz), the tidal volume (25-100 ml), and the resident gas (He, N2, SF6). Tidal volume was measured with a body plethysmograph. Blood gases were measured after a quasi-steady state was established. The kinematic viscosity of the breathing gas mixture, which changed by 1,700%, was found to have little effect on arterial PO2 and PCO2. The results are consistent with findings in a branched model that consisted of tubes with a diameter of 1 cm and with the theory of Taylor-type diffusion in turbulent flow. In addition, experiments were performed reducing and increasing the equipment dead space. This resulted in changes of PO2 and PCO2 that were appreciably less than those resulting from variations of tidal volume of the same magnitude. PMID- 1907605 TI - Differential respiratory effects of HCO3- and CO2 applied on ventral medullary surface of rats. AB - To estimate whether H+ is the unique stimulus of the medullary chemosensor, ventilatory effects of HCO3- and/or CO2 applied on the ventral medullary surface using an improved superfusion technique and of CO2 inhalation were compared in halothane-anesthetized spontaneously breathing rats. Superfusion with low [HCO3-] acid mock cerebrospinal fluid (CSF) (normal Pco2) induced a significant increase in ventilation, with an accompanying reduction in endtidal Pco2 (PETco2). High [HCO3-]-alkaline CSF depressed ventilation. Changes in Pco2 of superfusing CSF, on the other hand, had no significant effect despite the similar changes in pH. Simultaneous decrease in [HCO3-] and Pco2 of mock CSF with normal pH also maintained stimulated respiration. CO2 inhalation during superfusion with various [HCO3-] solutions caused further increase in ventilation as PETco2 increased. The results suggest that the surface area of the rat ventral medulla contains HCO3- (or H+)-sensitive respiratory neural substrates which are, however, little affected by CO2 in the subarachnoid fluid. A CO2 (or CO2-induced H+)-sensitive chemosensor responsible for the increase in ventilation during CO2 inhalation may exist elsewhere functionally apart from the HCO3- (or H+)-sensitive sensor in the examined surface area. PMID- 1907606 TI - Stimulation of secretion into human and feline airways by Pseudomonas aeruginosa proteases. AB - We have investigated the effect of elastase and alkaline protease from Pseudomonas aeruginosa on airway secretion into the trachea of anesthetized cats and from human bronchial mucosa in vitro. Secretory macromolecules were radiolabeled biosynthetically with two precursors in the cat, [3H]glucose and [35S]sulfate, and with [35S]-sulfate only in human tissue. Both enzymes (2.6 x 10(-9) to 1.3 x 10(-6)M elastase and 8 x 10(-9) to 2.4 x 10(-6)M alkaline protease) released radiolabeled macromolecules in a concentration-dependent manner from the two preparations. Purified elastase, 1.3 x 10(-6)M, released radiolabeled macromolecules (delta 3H = +397 +/- 72%, delta 35S 225 +/- 40% over control, P less than 0.001) and periodic acid-Schiff- (PAS) reactive glycoconjugates (delta PAS = +4.1 +/- 0.96 micrograms/min or +102 +/- 20%; P less than 0.01) from cat trachea, as did alkaline protease, 2.4 x 10(-6)M (delta 3H = +356 +/- 57%, delta 35S = +176 +/- 25%, delta PAS = +7.5 +/- 1.3 micrograms/min or 194 +/- 36%, P less than 0.001). Increases in 3H exceeded those of 35S, suggesting surface epithelium as the main source of secretion. Inhibition of enzyme activity abolished secretory effects. Both enzymes also stimulated secretion from human bronchus (e.g., with elastase, 1.3 x 10(-6)M: delta 35S = +331 +/- 67%, delta PAS = +4.3 +/- 0.92 micrograms/min or +131 +/- 24%, P less than 0.001; with alkaline protease, 2.4 x 10(-6)M: delta 35S = +220 +/- 67%, delta PAS = +12.7 +/- 3.2 micrograms/min or +575 +/- 245%, P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1907607 TI - Corticosteroid and thyrotropin-releasing hormone effects on preterm sheep lung function. AB - Four groups of twin sheep fetuses were catheterized at 121 days of gestational age and intravenously infused with saline, 0.75 mg.kg-1.h-1 cortisol for 60 h, five intermittent bolus injections of 5 micrograms/kg thyrotropin-releasing hormone (TRH) at 12-h intervals, or both hormones before delivery at 128 days. At birth, the lambs were randomized to receive surfactant or no treatment. Surfactant treatment improved lung function of all the groups. Corticosteroids alone and in combination with TRH improved compliance and gas exchange as well as pressure-volume curves. Corticosteroids alone dramatically decreased the recovery of intravenously administered radiolabeled albumin in the lung tissue and air space and improved the pulmonary response to surfactant treatment. There were no additional effects of TRH when given with corticosteroids on lung function or albumin leak. There were no changes in alveolar surfactant-saturated phosphatidylcholine pool sizes after any hormone treatment. The single significant effect of combined corticosteroid and TRH treatment was a fivefold increase in surfactant protein A in alveolar lavage fluid relative to all other groups. PMID- 1907608 TI - Sensitive immunoradiometric assay for the detection of Paracoccidioides brasiliensis antigens in human sera. AB - In the present study we report the standardization of an immunoradiometric assay (IRMA) for detection of Paracoccidioides brasiliensis circulating antigens that could be useful in the diagnosis and prognosis of paracoccidioidomycosis. For this purpose we studied the reactivities of P. brasiliensis and other mycotic antigens with rabbit polyclonal anti-P. brasiliensis antibodies (immunoglobulin G) in order to evaluate the sensitivity and specificity of an IRMA for detecting P. brasiliensis antigens. The results were compared with those obtained by the double immunodiffusion test, the standard technique for the serodiagnosis of paracoccidioidomycosis. By using the immunoglobulin G fraction of rabbit antisera (900 ng per well), it was possible to detect up to 3.6 ng (0.12 micrograms/ml) of cellular antigen and 360 ng (12 micrograms/ml) of metabolic antigen in contrast to the double immunodiffusion test that could detect only 12 micrograms (1.2 mg/ml) of both antigens. IRMA was shown to be feasible and very sensitive and may therefore help, together with clinical data, in establishing early diagnosis and assessing disease activity. It could also allow the study of relationships between P. brasiliensis circulating antigens and host defense mechanisms during the disease. PMID- 1907609 TI - Detection of enterococcal high-level aminoglycoside resistance with MicroScan freeze-dried panels containing newly modified medium and Vitek Gram-Positive Susceptibility cards. AB - Both conventional and modified MicroScan Type 5 panels and Vitek Gram-Positive Susceptibility cards were compared with agar dilution screen plates for their abilities to detect high-level resistance to gentamicin and streptomycin in 235 enterococcal isolates, including 167 Enterococcus faecalis and 63 E. faecium isolates. The modified Type 5 panels contained dextrose-phosphate broth instead of Mueller-Hinton broth in their high-level-resistance screen wells. The sensitivities for detection of gentamicin and streptomycin high-level resistance were 100 and 100% (E. faecalis) and 100 and 94% (E. faecium) for the modified MicroScan panels, 100 and 89% (E. faecalis) and 100 and 98% (E. faecium) for the conventional MicroScan panels, and 81 and 86% (E. faecalis) and 85 and 94% (E. faecium) for the Vitek cards. All specificities were 100% except for the Vitek cards with streptomycin, where it was 96%. Isolates that showed resistance on the streptomycin agar screen plates were rescreened on plates containing 32,000 micrograms/ml to detect ribosomally mediated resistance. For all three systems, every failure to detect streptomycin high-level resistance occurred in isolates with enzymatic, not ribosomal, resistance. The modified MicroScan Type 5 panels are a suitable method for detecting enterococcal high-level resistance to gentamicin and streptomycin. The Vitek cards are too insensitive for this purpose. PMID- 1907610 TI - Comparison of the new MicroScan Pos MIC Type 6 panel and AMS-Vitek Gram Positive Susceptibility Card (GPS-TA) for detection of high-level aminoglycoside resistance in Enterococcus species. AB - We compared the MicroScan Pos MIC Type 6 panel and AMS-Vitek Gram Positive Susceptibility Card (GPS-TA) to agar dilution screen plates for the detection of high-level aminoglycoside resistance in 182 enterococcal isolates. The specificity of the two commercial systems was 100%, with the exception of one susceptible isolate found to be streptomycin resistant by the Vitek system. The MicroScan and Vitek systems had comparable sensitivities for the detection of gentamicin resistance (90 and 95% respectively) and streptomycin resistance (85 and 78%, respectively). These results suggest that screening tests such as agar dilution screen plates, broth dilution, or disk diffusion should continue to be used to detect high-level gentamicin and streptomycin resistance. PMID- 1907611 TI - Nosocomial acquisition of Pseudomonas aeruginosa by cystic fibrosis patients. AB - During a 4-year period, at least 12 of 40 patients with cystic fibrosis (CF) who were newly colonized with Pseudomonas aeruginosa had acquired it at CF recreation camps, clinics, or rehabilitation centers. After introduction of hygienic precautions at the CF clinic, only a single episode of nosocomial transmission of P. aeruginosa was detected at the CF ward during the subsequent 2 years. PMID- 1907612 TI - Genotypic identification of pathogenic Mycobacterium species by using a nonradioactive oligonucleotide probe. AB - Commercial DNA hybridization assays (Syngene, Inc., San Diego, Calif.) utilizing alkaline phosphatase-labeled oligonucleotide probes for the identification of Mycobacterium tuberculosis complex and M. avium complex (MAC) were evaluated with 261 isolates of mycobacteria. On the basis of biochemical criteria, the test for MAC was 98% specific and more sensitive (95 of 99, 95%) than Gen-Probe (88 of 99, 89% sensitivity); the major difference in sensitivity noted between the two systems was related to the hybridization of seven MAC strains to the SNAP X probe. The M. tuberculosis complex probe correctly identified all 62 isolates of M. tuberculosis and all 11 isolates of M. bovis, for a sensitivity of 100%. There were two discrepant reactions with mycobacteria other than M. tuberculosis complex isolates. PMID- 1907613 TI - Effector mechanisms in organ-specific autoimmunity. I. Characterization of a CD8+ T cell line that mediates murine interstitial nephritis. AB - To further investigate mechanisms of cell-mediated tissue destruction in an organ specific autoimmune disease, we have established and characterized a nephritogenic CD8+ T cell line. This target antigen-specific effector T cell line, M52, was derived from bulk populations of CD8+ T cells isolated from susceptible animals immunized to produce anti-tubular basement membrane (alpha TBM) disease. Our studies show that M52 retains the phenotypic and functional characteristics of nephritogenic T cells induced in vivo. M52 mediates antigen specific delayed-type hypersensitivity (DTH) responses to the target antigen 3M 1, it is cytotoxic to 3M-1-expressing renal tubular epithelial cells in vitro, and it adoptively transfers interstitial nephritis to naive syngeneic recipients. Clonal analysis of these nephritogenic CD8+ T cells reveals distinct functional phenotypes within the M52 cell line. We have isolated a cytotoxic CD8+ clone, M52.26, which is not DTH-reactive to 3M-1, and multiple DTH-reactive clones which mediate less efficient cytotoxicity to 3M-1-expressing target cells. Cytofluorographic analysis of four randomly selected clones reveals alpha beta T cell receptor expression. Further characterization of these functionally distinct CD8+ T cell clones will help to define their respective roles in mediating tubular epithelial cell injury and the inflammatory lesion of autoimmune interstitial nephritis. PMID- 1907614 TI - ATP-dependent K+ channels modulate vasoconstrictor responses to severe hypoxia in isolated ferret lungs. AB - In normo- and hypoglycemic ferret lungs, the pulmonary vascular response to severe hypoxia (PiO2 less than or equal to 10 mmHg) is characterized by an initial intense vasoconstriction followed by marked vasodilation, whereas in hyperglycemic lungs, vasodilation is minimal, causing vasoconstriction to be sustained. In contrast, the response to moderate hypoxia is characterized by a slowly developing sustained vasoconstriction which is unaffected by glucose concentration. To determine the role of ATP-dependent K+ (KATP) channels in these responses, we examined the effects of cromakalim, which opens KATP channels, and glibenclamide, which closes them. During steady-state vasoconstriction induced in isolated ferret lungs by moderate hypoxia, cromakalim caused dose-dependent vasodilation (EC50 = 7 x 10(-7) M) which was reversed by glibenclamide (IC50 = 8 x 10(-7) M), indicating that KATP channels were present and capable of modulating vascular tone. During severe hypoxia in hypoglycemic lungs [( glucose] less than 1 mM), glibenclamide markedly inhibited the secondary vasodilation. Raising perfusate glucose concentration to 14 +/- 0.4 mM had the same effect. As a result, initial vasoconstrictor responses were well sustained. However, neither glibenclamide nor hyperglycemia affected vasoconstrictor responses to moderate hypoxia or KCl, indicating that effects during severe hypoxia were not due to nonspecific potentiation of vasoconstriction. These findings suggest that in the ferret lung (a) severe hypoxia decreased ATP concentration and thereby opened KATP channels, resulting in increased K+ efflux, hyperpolarization, vasodilation, and reversal of the initial vasoconstrictor response; and (b) hyperglycemia prevented this sequence of events. PMID- 1907615 TI - Activation of human monocyte--derived macrophages with lipopolysaccharide decreases human immunodeficiency virus replication in vitro at the level of gene expression. AB - Activation of T lymphocytes infected with the human immunodeficiency virus-1 (HIV 1) results in enhancement of viral replication mediated in part by activation of cellular NF kappa B capable of binding directly to sequences in the viral long terminal repeat, or LTR. Together with CD4+ T cells, macrophages constitute a major target for infection by HIV-1. Unlike lymphocytes, however, stimulation of mononuclear phagocytes is not associated with cell division and proliferation. Human monocyte-derived macrophages transfected with HIV-LTR-CAT constructs demonstrated down-regulation of CAT activity after stimulation with bacterial lipopolysaccharide (LPS) that mapped to a region distinct from NF kappa B binding sites. In contrast, fresh monocytes and the promonocytic U937 cell line both demonstrated up-regulation of HIV-LTR-CAT expression by LPS. Differentiation of U937 by PMA to establish a nondividing phenotype resulted in down-regulation of transfected HIV-LTR-CAT activity by LPS similar to that in mature macrophages. Human monocyte-derived macrophages infected with HIV-1 in vitro demonstrated a decrease in viral p24 release after incubation in LPS that was comparable to the negative regulation that occurred in the transient transfection assays. Factors controlling HIV replication may differ in dividing and nondividing hematopoietic cells and may contribute to restricted viral expression in nondividing cells. PMID- 1907616 TI - Lysosomal alpha-N-acetylgalactosaminidase deficiency, the enzymatic defect in angiokeratoma corporis diffusum with glycopeptiduria. AB - Recently a novel case of angiokeratoma corporis diffusum with glycoaminoaciduria was described in a 46-yr-old Japanese woman. Known causes of the cutaneous manifestation were eliminated by enzyme analyses, and further characterization of the accumulated urinary O-linked sialopeptides revealed identity to those excreted by patients with an infantile neuroaxonal dystrophy due to lysosomal alpha-N-acetylgalactosaminidase deficiency. Investigation of the alpha-N acetylgalactosaminidase activity and protein in the proband revealed less than 2% of normal activity and the absence of detectable immunoreactive enzyme protein, findings comparable to those in the patients with infantile neuroaxonal dystrophy and alpha-N-acetylgalactosaminidase deficiency. In addition, the proband's unaffected offspring had half-normal levels of alpha-N-acetylgalactosaminidase activity, consistent with this enzymatic deficiency being the primary metabolic defect in this autosomal recessive trait. Ultrastructural examination of skin and blood cells from the adult proband revealed the presence of prominent lysosomal inclusions containing diffuse amorphous and filamentous material. In contrast, these morphologic findings were not observed in the nonneural tissues from patients with infantile neuroaxonal dystrophy and alpha-N-acetylgalactosaminidase deficiency. These studies document the occurrence of two forms of alpha-N acetylgalactosaminidase deficiency and sialopeptiduria, a severe infantile-onset form of neuroaxonal dystrophy without angiokeratoma or visceral lysosomal inclusions and an adult-onset form characterized by angiokeratoma, extensive lysosomal accumulation of sialoglycopeptides and the absence of detectable neurologic involvement. PMID- 1907617 TI - Immunoblotting and culture positive endocarditis. AB - Serum samples from patients with endocarditis due to Streptococcus mutans, Streptococcus pneumoniae, Streptococcus agalactiae, Streptococcus lactis and a "nutritionally" variant streptococcus were immunoblotted against antigenic extracts from all five species. In S mutans endocarditis there was an endocarditis specific pattern of IgM against bands of 220, 200, and 190 kilodaltons. In S pneumoniae IgM against antibody of a molecular weight greater than 150 kilodaltons was specific to endocarditis. In S agalactiae IgM against bands at 82, 71, and 66-67 kilodaltons was endocarditis specific. In S lactis endocarditis specific IgM was present against antigenic bands at 105, 66, 61 and 58 kilodaltons. With the "nutritionally" variant streptococcus it was impossible to distinguish between cases of endocarditis and controls. PMID- 1907618 TI - Laboratory detection of ciprofloxacin resistant Neisseria gonorrhoeae. AB - During 1989 and 1990 strains of Neisseria gonorrhoeae with reduced susceptibility to ciprofloxacin were isolated in laboratories across the United Kingdom. Treatment failures were associated with some of these infections. These strains were detected by quantitative susceptibility testing because the zone of inhibition around 5 micrograms ciprofloxacin discs shows little decrease in size even with those that are the most resistant. This study determined that strains with reduced susceptibility to ciprofloxacin (MIC of greater than or equal to 0.05 mg/l) produced no zone of inhibition around a commercially available disc containing 30 micrograms of nalidixic acid. Ciprofloxacin sensitive (MIC of less than 0.05 mg/l) strains, however, grew with a large zone (greater than 21 mm) around this disc. These observations suggest that laboratories could adopt this disc test to detect those strains for which ciprofloxacin is not appropriate treatment. PMID- 1907619 TI - Hepatitis C virus and transfusion transmitted liver disease. PMID- 1907620 TI - Immature lymphocytes in transient erythroblastopenia of childhood. PMID- 1907621 TI - Breast abscess following central venous catheterization. AB - We describe a case of late perforation of the right internal mammary vein by a central venous catheter inserted via the left subclavian vein. This resulted in extravasation of parenteral nutritional fluid and breast abscess formation. Delay in reaching the diagnosis was experienced in this case and in two cases previously reported. The clinical presentation was similar in all three cases with good early function of the catheters followed by symptoms of chest pain and signs of inflammation in the breast contralateral to the site of insertion of the central venous catheter. Confirmation of correct placement of the central venous catheter must be sought in any patient who develops these symptoms or signs so that the delay in diagnosis we experienced can be avoided. This may be obtained by a lateral or oblique chest radiograph or by contrast studies if preferable. PMID- 1907622 TI - Non-invasive pulmonary blood flow measurement by means of CO2 analysis of expiratory gases. AB - Two different methods of CO2-derived non-invasive assessment of the pulmonary blood flow were evaluated. The principle of the formula, as proposed by Gedeon et al., is based on a rapid change in arterial CO2 content and subsequent changes in endtidal PCO2 and CO2 elimination. Both methods were compared to thermodilution cardiac output in 44 postoperative patients after CABG. The first method consisted of a short period of hyperventilation followed by hypoventilation. Comparison with the thermodilution cardiac output showed a low correlation coefficient: using a measured arterial--end-tidal PCO2 difference (E) r = 0.397 was found. Entering a fixed E of 0.53 kPa resulted in r = 0.454. These disappointing figures may be explained by procedural mistakes. The second method, based on partial rebreathing by means of adding an additional dead space of 220 ml for 30-45 s, correlated very well with the thermodilution findings. Correlation coefficients of r = 0.925 (measured E) and r = 0.925 (fixed E) were found. Considering the simplicity of the method, the additional dead space approach seems to be an easy and reliable way to determine pulmonary blood flow. PMID- 1907624 TI - Building a professional environment in long-term care. The role of clinical career development. AB - 1. To be successful, an organizational career development program must include a differentiation of the responsibilities for which the various parties (employer, employee, career counselor) will be held accountable. 2. Project outcomes revealed that the career mobility program was attractive to nursing personnel and facility management personnel alike. However, it was more attractive to nonlicensed than licensed personnel. 3. Of the staff who participated and were promoted, the majority remained in their jobs. The program was most successful in enhancing retention with personnel who received within-level promotions. 4. The process of career development requires collaboration and support from all levels of leadership and staff throughout the organization. A career development program, including a career mobility program with a strong career counseling component, can serve as a catalyst in professionalizing the long-term care work environment. PMID- 1907623 TI - Chronic exposure to glibenclamide impairs insulin secretion in isolated rat pancreatic islets. AB - We investigated the effect of 24 h exposure to 100 nmol/l glibenclamide on insulin secretion in isolated rat pancreatic islets. The insulin content was similar in control islets and in islets preincubated with 100 nmol/l glibenclamide for 24 h. In islets preexposed to glibenclamide: 1) the subsequent response to a maximal glibenclamide stimulatory concentration (10 mumol/l, 1 h at 37 C) was greatly reduced in comparison to control islets (0.69 +/- 0.20% vs 2.16 +/- 0.41%; mean +/- SE; n = 14; p less than 0.001); 2) the response to 100 mumol/l tolbutamide stimulation was also reduced (0.55 +/- 0.15% vs 2.38 +/- 0.44%; n = 8; p less than 0.001); 3) the response to 16.7 mmo/l glucose, both in the presence or in the absence of 1 mmol/l IBMX, a phosphodiesterase inhibitor, was also diminished by about 50% (1.79 +/- 0.39% vs. 3.22 +/- 0.42%; n = 14, p less than 0.001). In glibenclamide pretreated islets, blunted responses to stimuli were confirmed also by dynamic studies using a perifusion system. The effect of glibenclamide preincubation was fully reversible: when islets cultured in the presence of glibenclamide were transferred to a glibenclamide-free medium for further 24 h, insulin release in response to glibenclamide stimulation returned to control values. We conclude that prolonged exposure of rat pancreatic islets to glibenclamide induces a reversible desensitization to a variety of metabolic stimuli. The inhibition by prolonged glibenclamide exposure of a common pathway in the mechanism of insulin release is one possible explanation for these results. PMID- 1907625 TI - Disinfection practices for endoscopes and other semicritical items. AB - OBJECTIVE: To determine the disinfection practices employed by North Carolina hospitals for endoscopes and other semicritical patient care items and to discuss minimally acceptable disinfection procedures for these items. DESIGN: A survey questionnaire was mailed to all North Carolina hospitals to identify their disinfection practices, and a literature review was conducted to ascertain studies that evaluated disinfection techniques for certain semicritical items. PARTICIPANTS: Questionnaires were returned by 107 of 167 (64%) North Carolina acute-care hospitals. RESULTS: Most hospitals (91%) used a glutaraldehyde-based disinfectant (59%, 2% glutaraldehyde; 29%, 0.13% glutaraldehyde-0.44% phenol 0.08% phenate; 3%, either); half (51%) of the hospitals immersed the endoscope into disinfectant for greater than or equal to 20 minutes, but 44% immersed for less than or equal to 10 minutes; nearly all hospitals (97%) disinfected endoscopes at room temperature. Hospitals rinsed the endoscope with sterile water (16%), tap water (54%), tap water followed by alcohol rinse (27%), or other (2%); 58% of the hospitals treated endoscopes from patients infected with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or Mycobacterium tuberculosis differently (81%, ethylene oxide [ETO] sterilization; 10%, increased exposure time; 10%, other). Twenty percent of the hospitals used an automated washer for processing endoscopic instruments. Rigid endoscopes (e.g., arthroscopes, laparoscopes) were primarily high-level disinfected (57%), ETO sterilized (17%), or either (13%). The disinfection strategies for other semi critical items (e.g., applanation tonometers, cryosurgical instruments, and diaphragm fitting rings) were highly variable for the responding hospitals. CONCLUSIONS: This survey indicated the presence of a wide variety of practices for handling semicritical patient care items, many of which are inconsistent with current recommendations. To help establish minimally acceptable disinfection procedures for some patient care instruments (e.g., arthroscopes, laparoscopes, tonometers), the scientific literature was reviewed and recommendations were made. PMID- 1907626 TI - Listeria. PMID- 1907627 TI - Detection of glomerular anionic sites in post-embedded ultra-thin sections using cationic colloidal gold. AB - We detected glomerular anionic sites in fixed, LR Gold-embedded ultra-thin tissue sections using cationic colloidal gold. Manual and computer-assisted quantitation were compared, and the influence of pH and glycosaminoglycan-degrading enzymes on site expression was examined. Both quantitation methods produced similar results. Alteration of pH within a narrow range (pH 2.5-3.0) markedly affected the staining pattern. At pH 2.5, epithelial and endothelial glycocalyx and regular sites restricted to the lamina rara externa were stained. At pH 3.0 and above, glycocalyx was unstained but intracellular and nuclear staining was present; glomerular basement membrane (GBM) and mesangial matrix sites were abundant. After chondroitinase ABC or hyaluronidase digestion, GBM staining was eliminated at pH 2.0 and reduced at pH 7.0 (p less than 0.001), suggesting that degraded sites are associated with chondroitin sulfate or hyaluronic acid. By contrast, prolonged heparitinase I digestion was ineffective at either pH. Digestion of purified substrates revealed crossreactivity of heparitinase towards chondroitin sulfate and of chondroitinase towards hyaluronic acid. Since tissue sites were reduced by chondroitinase but not heparitinase, we suggest that degradation is due to hyaluronidase activity of chondroitinase and the anionic sites are associated with hyaluronic acid. However, the influence of pH indicates that lamina rara externa sites are structurally distinct from other GBM anionic sites. PMID- 1907628 TI - A new technique, requiring small amounts of cells, for the parallel study of chemiluminescence and phagocytosis via different receptors in the same cell population. AB - An assay permitting the parallel assessment of phagocytosis and chemiluminescence in the same cell population has been developed. The method is based on the phagocytosis of fluorescein isothiocyanate-conjugated yeast particles, either unopsonized or opsonized with complement factor C3 or IgG, by purified cells in suspension in a luminometer. Only a small number of cells (2 x 10(4)-1 x 10(5)) is required, and the reproducibility is high. Moreover, the technique permits phagocytosis to be related to oxygen-dependent killing activity in the same cell population. Since phagocytosis, degranulation and oxygen radical formation as a consequence of well-defined receptor recognition mechanisms can be characterized in very small cell populations, the method is suitable for monitoring the phagocytic function of cells from extravascular sites. PMID- 1907629 TI - [Regulation of arachidonate cascades by protein kinase C action]. PMID- 1907630 TI - [Structure and biological activities of LIF/D-factor]. PMID- 1907631 TI - [Necessity and schedule of infusion therapy in water-electrolyte imbalance]. PMID- 1907632 TI - [Infusion therapy of water-electrolyte imbalance]. PMID- 1907633 TI - [Parenteral hyperalimentation therapy of water-electrolyte imbalance]. PMID- 1907634 TI - [A case of allergic granulomatous angitis with factor VIII inhibitor]. PMID- 1907635 TI - Electron microscopic visualization of actin filaments in the early embryo of Drosophila melanogaster: the use of phalloidin and tropomyosin. AB - Various specimen preparations for thin-section electron microscopy were tested to better preserve and visualize actin filaments in the cortex of the early embryos of Drosophila melanogaster. When embryos were treated with phalloidin prior to fixation, many actin filaments were observed in their cortex comparable to the staining with fluorescently labeled phalloidin in light microscopy. Then we used various fixatives containing phalloidin. As far as we examined, actin filaments were best preserved in the specimen fixed with 2.5% glutaraldehyde, 2% paraformaldehyde in 0.1 M sodium phosphate buffer or in 0.1 M PIPES buffer (1 mM EGTA and 1 mM MgCl2) containing 10 microM phalloidin and 0.1% saponin. When embryos were glycerinated and then treated with tropomyosin before fixation, actin filaments were well visualized as thicker, uniform-sized filaments, though the number of filaments decreased probably owing to glycerination. This suggests that, like heavy meromyosin and its subfragment-1, this protein may protect actin filaments from being disrupted by chemical fixation. Using these improved fixation procedures, we successfully examined the distribution of actin filaments in the Drosophila embryo cortex during cellularization. These methods may be applicable to stabilize labile actin filaments in other types of cells. PMID- 1907636 TI - Regulation of the oxidative stress response by the hpr gene in Bacillus subtilis. AB - Bacillus subtilis mutants with null mutations in the spo0 A gene are resistant to oxidative stress during the exponential phase of growth. This resistance phenotype can be suppressed by mutations in the abrB gene, or in the hpr gene. Both of these gene products are negative regulatory proteins which are over produced in a spo0 A strain, and the over-production of the hpr gene product results from over-production of the abrB gene product. The results suggested that the resistance to oxidative stress in a spo0 A strain is due to the lack of a protein directly controlled by the hpr negative regulator. Other mutations in the spo0 A gene conferring resistance to ethanol stress (eth) or suppressors of sporulation phenotypes (sof) had no effect on the sensitivity to oxidative stress of strains bearing them. PMID- 1907637 TI - Bacillus licheniformis APase I gene promoter: a strong well-regulated promoter in B. subtilis. AB - The 5' regulatory region and the portion of the structural gene coding for the amino-terminal sequence of alkaline phosphatase I (APase I) were isolated from Bacillus licheniformis MC14 using a synthetic oligodeoxynucleotide deduced from the amino acid sequence of the enzyme. The DNA sequence analysis of this region revealed an open reading frame of 129 amino acids containing the amino-terminal sequence of the mature APase protein. The protein sequence was preceded by a putative signal sequence of 32 amino acid residues. The predicted amino acid sequence of the partial APase clone as well as the experimentally determined amino acid sequence of the enzyme indicated that B. licheniformis APase retains the important features conserved among other APases of Bacillus subtilis, Escherichia coli, Saccharomyces cerevisiae, and various human tissues. Heterologous expression studies of the promoter using a fusion with the lacZ gene indicated that it functions as a very strong inducible promoter in B. subtilis that is tightly regulated by phosphate concentration. PMID- 1907638 TI - Identification of aecA mutations in Bacillus subtilis as nucleotide substitutions in the untranslated leader region of the aspartokinase II operon. AB - Recent genetic mapping of the aspartokinase II (lysC) operon of Bacillus subtilis [M. Petricek. L. Rutberg & L. Hederstedt (1989) FEMS Microbiology Letters 61, 85 88; N.Y. Chen. J. J. Zhang & H. Paulus (1989) Journal of General Microbiology 135, 2931-2940] has shown its chromosomal location to be close to the aecA locus, the mutation of which leads to highly increased levels of aspartokinase II. In order to examine the relationship between lysC and aecA, we have cloned the control regions of the lysC operon from several independent aecA mutants and determined their nucleotide sequences. The nucleotide sequences of the aecA mutants differed from the wild-type sequence by the substitution of one or two nucleotides at two widely separated sites in the transcribed leader region of the lysC operon. To confirm that the observed nucleotide changes are indeed responsible for the AecA phenotype and not simply the reflection of sequence polymorphisms in different B. subtilis strains, we introduced the same nucleotide substitutions as those observed in the aecA strains into the leader region of the wild-type lysC operon by oligonucleotide-directed mutagenesis. The expression of the mutagenized genes was analysed after transcriptional or translational fusion to lacZ in a single-copy integration vector. The levels of beta-galactosidase were greatly elevated by the nucleotide substitutions, with similar increases observed in transcriptional and translational fusions. The high level of expression of beta-galactosidase in the lysC'-lac'Z strains with nucleotide substitutions corresponding to the aecA mutations was resistant to repression by L-lysine but was completely abolished by the inactivation of the lysC promoter.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1907639 TI - Trial of a negative ion generator device in remediating problems related to indoor air quality. AB - It has been suggested that supplementation of indoor air with negative ions can improve air quality. This study examined the effects of a "negative ion generator" device on air contaminants and symptom reporting in two office buildings. Separate sets of functional and nonfunctional negative ion generators were monitored using a double blind, crossover design involving two 5-week exposure periods. There were no detectable direct or residual effects of negative ion generator use on air ion levels, airborn particulates, carbon dioxide levels, or symptom reporting. Symptom reporting declined at both sites initially and appeared to be consistent with placebo effect. Job dissatisfaction was an apparent contributor to symptom reporting, with a magnitude comparable to presumed effects of air quality. Further testing of such devices is needed before they should be considered for office air quality problems. PMID- 1907640 TI - Mechanisms of photodynamic effects of furocoumarins. AB - The photosensitizing action of furocoumarins on biological systems occurs by both an oxygen-independent pathway, which involves the photoaddition of the sensitizer to nucleic acids, proteins and lipids, and an oxygen-dependent pathway, which includes furocoumarins in the category of photodynamic sensitizers. The photodynamic action of furocoumarins, as studied using isolated biomolecules, human erythrocytes and human skin, appears to involve both activated oxygen species (singlet oxygen, superoxide anion, and hydroxyl radicals) and radical species formed by electron transfer from or to photoexcited furocoumarins. Another oxygen-dependent process involves the formation of photo-oxidized furocoumarin derivatives, which can react in the dark with several substrates (in particular, membrane components), causing an irreversible damage of cells. The latter type of process is temperature dependent. The relative importance of the different photosensitization mechanisms under various experimental conditions is discussed. PMID- 1907641 TI - Activity of thiols as singlet molecular oxygen quenchers. AB - Singlet molecular oxygen O2(1 delta g) arising from the thermodissociation of the endoperoxide of 3,3'-(1,4-naphthylidene) dipropionate (NDPO2) was used to assess the quenching ability of various thiols and related compounds in sodium phosphate buffer in D2O at 37 degrees C. The overall quenching ability decreases in the sequence ergothioneine, methionine, cysteine, beta,beta-dimethyl cysteine (penicillamine), mercaptopropionylglycine, mesna, glutathione (GSH), dithiothreitol, N-acetyl cysteine and captopril. Cystine, glutathione disulphide, dimesna, methionine sulphone and methionine sulphoxide have no quenching effect. Comparison of the rate constants for physical (kq) with chemical (kr) quenching by thiols indicates that chemical reactivity accounts fully for their ability to quench O2(1 delta g), and pD dependence indicates that the thiolate anion reacts with O2(1 delta g). Loss of thiol groups, as exemplified by GSH, is not affected by the free radical scavengers superoxide dismutase and mannitol. However, sodium azide, a scavenger of O2(1 delta g), completely prevents NDPO2-induced thiol depletion. Depletion of GSH by NDPO2 is accompanied by the formation of its disulphide, sulphinate, sulphonate, sulphoxide and other products. PMID- 1907642 TI - Photodynamic therapy of brain tumours--post-operative "field fractionation". PMID- 1907643 TI - Photodynamic therapy for ocular tumors. PMID- 1907644 TI - Potential of photodynamic therapy in the treatment of pharyngeal tumours: the clinical point of view. PMID- 1907645 TI - Photochemical and photobiological properties of 4,8-dimethyl-5'-acetylpsoralen. AB - The photochemical and photobiological properties of 4,8-dimethyl-5' acetylpsoralen (AcPso), proposed for the photochemotherapy of some skin diseases, were investigated. The photoreaction of AcPso with DNA is weaker in the presence of air than in a nitrogen atmosphere, in terms of total photobinding and DNA cross-linking; when UVA irradiation is performed in air, AcPso behaves as a monofunctional reagent. The quenching effect of oxygen is related to the high capacity of AcPso to produce singlet oxygen. Furthermore, it is demonstrated that AcPso photoadducts are better producers of singlet oxygen than free AcPso in solution. Using DNA sequencing methodology, two modes of DNA photosensitization by AcPso are shown, these lead to the formation of photoadducts mainly at T residues (and at C to a lesser extent) and to photo-oxidized G residues probably via singlet oxygen. Chemical or enzymatic cleavage were used as probes in these experiments. A rapid assay for the detection of the photodynamic effect of a photosensitizer on DNA, involving oxygen, is also described. Finally, the cytotoxicity and genotoxicity of AcPso on E. coli WP2 cells appear to be related to its ability to form photoadducts, in particular cross-links, rather than to its capacity to produce singlet oxygen. PMID- 1907646 TI - Preparative, analytical and fluorescence spectroscopic studies of sulphonated aluminium phthalocyanine photosensitizers. AB - Fluorescence spectroscopic studies were carried out on aluminium phthalocyanine with defined numbers (mono, di, tri and tetra) of sulphonate groups. Selective sulphonation was achieved using one of two synthetic methods to prepare a mixture of components which were separated using reverse-phase liquid chromatography. Fluorescence lifetimes were measured in methanol and buffer solution using time correlated single-photon counting with picosecond laser excitation; the lifetime shows little variation with the number of sulphonate groups. Using steady state excitation, fluorescence quantum yields were determined for the tetrasulphonated component (phi F = 0.51) and, for comparison, unsulphonated aluminium phthalocyanine. PMID- 1907647 TI - Photoprotection by melanin. AB - This paper is an attempt to summarize the current state of information on melanin and epidermal melanin pigmentation (EMP) as photoprotective agents. The chemistry and biochemistry of melanin (the particle) and its interaction, in its various forms, with UV radiation are considered. Methods of attenuation of UV radiation are discussed in terms of structure and chemical constituents. Photoprotection by constitutive and facultative pigmentation is reviewed with minimum erythema dose (MED) as the end point. The issue of acclimatization to UV radiation is discussed in terms of UVB phototherapy for psoriasis. Finally, skin cancer is considered as an end point and the reduction of its incidence with pigment level is discussed. It is concluded that whilst EMP provides protection, its extent depends on the end point chosen for evaluation. MED is a convenient photobiological end point but is rather insensitive, whereas skin cancer is sensitive but impractical for laboratory studies. Our current state of knowledge of melanin lacks information on its absorption and scattering coefficients and its refractive index. Methods for the quantitative measurement of EMP are also urgently required. PMID- 1907648 TI - Dark interaction of 5-methoxypsoralen and 8-methoxypsoralen with erythrocyte ghosts: a fluorescence and circular dichroism study. AB - The dark interaction of 5-methoxypsoralen (5-MOP) and 8-methoxypsoralen (8-MOP) with plasma membranes was studied using human erythrocyte ghosts as a model. In the presence of ghosts, modifications of the fluorescence characteristics of 5 MOP were observed, together with a quenching of the fluorescence of the tryptophan (Trp) residues of membrane proteins (up to 25%). Moreover, the appearance of an induced circular dichroism indicates that 5-MOP is located in a chiral environment. In contrast, only slight effects were observed in the case of 8-MOP. It is concluded that 5-MOP molecules are located partly within chiral protein sites of the membrane in such a way that a Forster energy transfer can occur from the Trp residues to the psoralen molecules. PMID- 1907649 TI - Changes in cell cycle distribution of V79 Chinese hamster fibroblasts after irradiation at different wavelengths. AB - Changes in cell cycle distribution of V79 Chinese hamster fibroblasts were investigated at different wavelengths between 254 and 313 nm. The fluences applied led to surviving fractions of 0.61. In all cases, the S fraction was temporarily increased within 8-12 h after irradiation, whereas the G1 fraction was decreased. The maximum deviations from the initial values did not significantly depend on the wavelength. PMID- 1907650 TI - A preliminary study of tumour detection by a pH-dependent fluorescent probe in vivo. PMID- 1907651 TI - Phototoxicity induced by nalidixic and oxolinic acids: decrease in cell survival of chick embryo fibroblasts and Hep-2 cells. AB - The phototoxic effects of nalidixic and oxolinic acids were evaluated in two types of cultured cells: chick embryo fibroblast and Hep-2 (human laryngo carcinoma cell line). In order to evaluate the phototoxicity induced by nalidixic and oxolinic acids, both cell types were irradiated for 5 min in the presence of each drug. The results showed an inverse relationship between cell survival and the concentration of the drug added to the culture medium. The concentrations of nalidixic and oxolinic acids necessary to induce a phototoxic effect were in the range of therapeutic blood levels. Both chick embryo fibroblasts and Hep-2 cells were more sensitive to the phototoxic effect induced by nalidixic acid than oxolinic acid. PMID- 1907652 TI - Ozone holes and biological consequences. PMID- 1907653 TI - Sarcocystis canis n. sp. (Apicomplexa: Sarcocystidae), the etiologic agent of generalized coccidiosis in dogs. AB - Sarcocystis canis n. sp. is proposed for the protozoon associated with encephalitis, hepatitis, and generalized coccidiosis in dogs. Only asexual stages are known in macrophages, neurons, dermal, and other cells of the body. The parasite is located free in the host cell cytoplasm without a parasitophorous vacuole; schizonts divide by endopolygeny. Schizonts are 5-25 x 4-20 microns and contain 6-40 merozoites. Merozoites are approximately 5-7 microns x 1 micron and do not contain rhoptries. The parasite is PAS-negative and reacts with Sarcocystis cruzi antiserum but not with Toxoplasma gondii, Neospora caninum, or Caryospora bigenetica antisera in an immunohistochemical test. PMID- 1907655 TI - Clinostomum attenuatum (Digenea) from the eye of Bufo marinus. AB - Two specimens of the cane toad, Bufo marinus, were found with single worm infestations of the eye. One worm was excysted in the eye chamber, the other still encysted in the choroid layer; both worms were identified as Clinostomum attenuatum. This finding is both a new host record and a new site of development for this amphibian parasite. PMID- 1907654 TI - The lesions and prevalence of Trypanosoma cruzi in opossums and armadillos from southern Louisiana. AB - The prevalence of Trypanosoma cruzi in 48 opossums and 98 armadillos from southern Louisiana was studied. Sixteen opossums (33.3%) and 1 armadillo (1.1%) were positive for T. cruzi by blood culture. Hearts from 45 opossums and the tissues from the 1 blood culture-positive armadillo were available for histopathological examination. Although histopathology revealed T. cruzi pseudocysts in 6 opossums, 2 were not positive on blood culture. Therefore, 18 opossums (37.5%) were positive for T. cruzi. Twenty-two of 45 opossums had histological evidence of myocarditis. No lesion typical of infection with T. cruzi was observed in the armadillo tissues. These results substantiate that the opossum is a current reservoir host of T. cruzi infection in southern Louisiana and that armadillos may be of relatively minor importance. PMID- 1907656 TI - The skunk Conepatus chinga as new host of Trypanosoma cruzi in Argentina. AB - We report the first systematic epidemiological research carried out in Argentina on the skunk Conepatus chinga. Forty-nine animals were captured in the settlements of Amama, Trinidad, and nearby forested areas located in the Department of Moreno, Province of Santiago del Estero, between April 1985 and May 1989. Isolation of parasites was done through xenodiagnosis, and their identification as Trypanosoma cruzi was achieved by biological and biochemical criteria. The isolate was highly virulent and pathogenic in inoculated C3H mice. Prevalence was 4.1% (2 of 49). Two facts account for a possible domestic source of infection: both infected skunks were captured near Trinidad, in an area that had never been treated with insecticides, and electrophoretic isoenzyme patterns of the parasites isolated from the skunks were identical to those found in humans. Because extensive deforestation probably would increase the distribution area of C. chinga, further investigation should be performed to evaluate the epidemiological role of this wild mammal. PMID- 1907657 TI - Rorschach changes in long-term and short-term psychotherapy. AB - Over a period of several years, repeat Rorschach testing was done with two groups of patients receiving outpatient psychotherapy, a long-term group (n = 88) engaged in intensive, dynamically oriented psychotherapy and a short-term group (n = 88) involved in behavioral or gestalt therapy. Rorschach protocols were obtained at the beginning of the treatment and on three subsequent occasions, 1 year, 2 1/2 years, and 4 years later, when most of the long-term and all of the short-term patients had completed their therapy. The findings demonstrate generally beneficial effects of psychotherapy, greater change in long-term than in short-term therapy, and the validity of the Rorschach for measuring these effects and changes. PMID- 1907658 TI - Characterization of the aqueous decomposition products of (+)1,2-bis(3,5 dioxopiperazinyl-1-yl)-propane (ICRF-187) by liquid chromatographic and mass spectral analysis. AB - High-performance liquid chromatography (HPLC) and fast atom bombardment mass spectrometry (FAB-MS) were employed to separate and identify the aqueous decomposition products of (+)1,2-bis(3,5-dioxopiperazinyl-1-yl)-propane (ICRF 187; 1), a drug active against several forms of human cancer and which also has recently been shown to display potent cardioprotective activity in patients treated with the antitumor antibiotic doxorubicin. Two reversed-phase HPLC columns were used to separate the hydrolysis products of 1, a Waters muBondapak phenyl column and an LKB Spherisorb ODS2 column. Incubation of 20 microM 1 in phosphate-buffered saline (PBS) at 37 degrees C for 21 h resulted in 47% decomposition, with three hydrolysis products detected (compound 2, Waters column retention time (RT) = 3.7 min, observed monoisotopic protonated molecular ion (MH+) m/z value of 305.1; compound 3, RT = 4.1 min, MH+ m/z value of 287.1; compound 4, RT = 4.8 min, MH+ m/z value of 287.1). The RT and MH+ m/z values for 1 were 17.1 min and 269.1, respectively. Based on the FAB-MS data, 2 corresponds to ICRF-198, the polar diacid diamide derivative of 1, while peaks 3 and 4 represent the monoacid monoamide derivatives of 1. Using B/E linked scan daughter FAB-MS analysis, 3 displayed a prominent fragment with a m/z value of 160, indicating that it corresponds to the monoacid monoamide derivative of 1, with the methyl group adjacent to the hydrolyzed ring. Compound 4, displaying a fragment with a m/z value of 142 in its B/E linked scan daughter ion spectrum, corresponds to the monoacid monoamide derivative of 1, with the methyl group adjacent to the closed ring. PMID- 1907659 TI - Selective effects of acute and chronic ethanol exposure on neuropeptide and guanine nucleotide stimulated phospholipase C activity in intact N1E-115 neuroblastoma. AB - The influence of acute and chronic ethanol exposures on the coupling of neurotensin and bradykinin receptors to phospholipase C was determined in intact N1E-115 cells. Phospholipase C was monitored by the formation of total [3H]inositol phosphates in the presence of lithium in cells prelabeled with [3H]inositol. Acute exposure to ethanol over a range of 50 to 200 mM inhibited the stimulation of [3H]inositol phosphate formation elicited by neurotensin and bradykinin. In cells chronically exposed to 100 mM ethanol for 7 days, neither basal- nor neurotensin-stimulated [3H]inositol phosphate formation differed significantly from those of control (untreated) cells. In contrast, the [3H]inositol response to bradykinin was significantly inhibited in cells chronically exposed to ethanol. Because chronic ethanol exposure had no parallel effects on either the specific binding of [3H]bradykinin or the stimulation of [3H]inositol phosphate formation by the stable GTP analog, guanine 5'-(y thiotriphosphate), it is suggested that chronic ethanol impairs the ability of bradykinin receptors to activate the guanine nucleotide binding protein associated with phospholipase C. In addition, because chronic ethanol had no effect on the inositol phosphate response to neurotensin, it is proposed that certain types of receptor-guanine nucleotide binding protein interactions are more vulnerable than are others to disruption by chronic ethanol treatment. PMID- 1907660 TI - Biotransformation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in primary cultures of mouse astrocytes. AB - Astrocytes are likely to be a main locus for the metabolic bioactivation of the neurotoxicant 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In this study, a detailed analysis of MPTP metabolism was conducted in primary cultures of mouse astrocytes. A constant rate of conversion of 1.22 nmol/mg of protein per hr was observed when astrocyte cultures were incubated in the presence of 250 microM MPTP for 4 days. Three metabolites were detected as products of this conversion: 1-methyl-4-phenyl-2,3-dihydropyridinium ion (MPDP+), 1-methyl-4-phenylpyridinium ion (MPP+) and MPTP N-oxide. Production of MPP+ and MPTP N-oxide occurred at constant rates of 0.68 and 0.43 nmol/mg of protein per hr, respectively, whereas the level of MPDP+ remained quite stable and relatively low throughout the time of incubation. Both clorgyline, an inhibitor of monoamine oxidase (MAO) type A, and deprenyl, a MAO B inhibitor, blocked MPTP conversion to MPDP+ and MPP+; quantitative analysis of the effects of these two inhibitors revealed that MAO A and MAO B contribute to a similar extent to MPP+ production in astrocyte cultures. MAO inhibition did not result in an increased production of MPTP N oxide and, in fact, the level of this metabolite was reduced markedly in the presence of 100 microM clorgyline. Formation of MPTP N-oxide was probably dependent upon the activity of the flavin-containing monooxygenase because: 1) it was blocked completely by thiobenzamide, a competitive substrate for this microsomal enzyme and 2) it was increased in the presence of n-octylamine, a known positive effector for flavin-containing monooxygenase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1907661 TI - Studies of concanavalin A in nonobese diabetic mice. I. Prevention of insulin dependent diabetes. AB - Concanavalin A (Con A) administered in vivo inhibited the development of insulin dependent diabetes mellitus (IDDM) in nonobese diabetic mice. By experimental day 310 only one of 10 Con A-treated animals had developed IDDM compared to six of 11 cohort controls receiving buffered saline and 65% of colony controls. Treatment consisted of an initial 70-day course of Con A at a dose of 10 micrograms/g b. wt., i.p. in sterile saline every other day. After two deaths occurred in the Con A group, treatment was stopped at day 70. The remaining animals were given two 1 week booster doses beginning on experimental days 118 and 189. The single animal in the Con A group that eventually developed IDDM at day 293 had not received an injection for 107 days. Histological examination revealed peri-islet lymphocytosis but no islet infiltration in the Con A group. Surviving control animals showed both peri-islet and islet infiltrates. One-week Con A treatment significantly suppressed in vitro responses of spleen cells to Con A and allogeneic lymphocytes. The treatment increased the frequency of "blast-sized" cells in vivo and decreased the CD4+/CD8+ ratio among resting splenocytes. It is concluded that polyclonal T cell activation by Con A provides protection against autoimmune diabetes in nonobese diabetic mice concomitant with phenotypic and morphologic lymphocyte changes. PMID- 1907662 TI - Comparison of patient-controlled analgesia and epidural morphine for postcesarean pain and recovery. AB - A greater awareness of the advantages and limitations of new methods of administering postcesarean analgesia would help the obstetrician care for the recovering patient. Patient-controlled analgesia and epidural morphine are two new modalities for postoperative pain relief. The purpose of this prospective investigation was to compare their effectiveness, safety, side effects, patient satisfaction and cost. During an eight-month period, 161 women undergoing cesarean delivery were assigned to receive narcotics by either epidural morphine (76 patients) or patient-controlled analgesia (85 patients) using a combined continuous infusion and demand dosing of meperidine. The demographic characteristics of the two groups were similar. Mild or no pain was reported with similar frequencies in both groups. No reduced respiration or undesired sedation was seen in either group. The postoperative times before sitting at the bedside, ambulating, tolerating clear liquids and leaving the hospital were also comparable. No complications were encountered with patient-controlled analgesia, but pruritus and alarms from apnea monitors occurred commonly in the epidural morphine group. The costs to the patient were similar for the two groups. Patient controlled analgesia using a combined continuous infusion and demand dosing is an acceptable alternative to epidural morphine after cesarean delivery. PMID- 1907663 TI - The effect of aurothiomalate on the oxidative burst of polymorphonuclear leukocytes varies with the quantity of drug in myocrisin ampoules. AB - The antirheumatic drug, sodium aurothiomalate (GSTM), is not a well defined substance and chemical changes occur in the heat sterilization of the commercial ampoules (Myocrisin). In a comparison of the pharmacological properties of Myocrisin with freshly prepared solutions of GSTM, their effects on the chemiluminescence of polymorphonuclear leukocytes (PMN) activated by phorbol myristate acetate (PMA) were studied. Chemiluminescence was measured in the presence of GSTM from solid material and from Myocrisin ampoules. Myocrisin from 1 and 5 mg ampoules and GSTM in fresh solutions heated at 95 degrees C for 30 min inhibited chemiluminescence, whereas Myocrisin from the higher strength (10-50 mg) ampoules and GSTM in unheated solutions showed no effect at low concentrations and enhancement of chemiluminescence at higher concentrations. Since the gold complexes present in the different strength Myocrisin ampoules do not have identical biological effects, the use of GSTM in investigational studies should involve consideration of its source. PMID- 1907664 TI - Dispensability of parts of histones and the molecular clock. PMID- 1907665 TI - The molecular evolution of ZFY-related genes in birds and mammals. AB - We report the isolation and nucleotide sequence determination of clones derived from five ZFY-related zinc-finger genes from birds and mammals. These sequences are analyzed with reference to the previously published human genes, ZFX and ZFY, and mouse genes, Zfx, Zfa, Zfy-1, and Zfy-2. The analysis indicates that ZFY related genes are highly conserved in birds and mammals, and that the rate of nucleotide substitution in the Y-linked genes is not as high as predicted. However, the mouse Zfy-1 and Zfy-2 genes are markedly divergent members of the ZFY gene family; we suggest this relates to X-inactivation of the mouse gene Zfx. PMID- 1907666 TI - Eukaryotic origins: string analysis of 5S ribosomal RNA sequences from some relevant organisms. AB - Using the PHYLOGEN tree-forming programs, we evaluate the published 5S rRNA sequences in certain of the files in the Berlin DataBank in an attempt to identify the connection between archaebacteria and the eukaryotic protists. These programs are based on methods of string analysis developed by Sankoff and others. Their discriminatory power is derived from their continuous realignment of sequences through repeated assessment of insertions and deletions as well as substitutions. The programs demonstrate that even these small molecules (ca. 120 bases) retain substantial records of evolutionary events that occurred over a billion years ago. The eukaryotes seem to have been derived from ancestors near the common origins of the halobacterial and Methanococcales groups. Identifying what might have been a primordial eukaryote is more difficult because several of the species considered as early derivatives from the common root are isolated species with large genetic differences from each other and from all other extant forms that have been sequenced. The ameboid, flagellated, and ciliated protists seem to have emerged nearly simultaneously from an ancient cluster, but the sarcodinid protozoa have preference as the group of most ancient origin. The euglenozoa and the ciliates are of later derivation. Our ability to tease plausible trees from such small molecules suggests that the mode of analysis rather than the size of the molecule is often a major limitation in the reconstruction of acceptable ancient phylogenics.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1907667 TI - A fast unbiased comparison of protein structures by means of the Needleman-Wunsch algorithm. AB - A fast dynamic programming algorithm for the spatial superposition of protein structure without prior knowledge of an initial alignment has been developed. The program was applied to serine proteases, hemoglobins, cytochromes C, small copper binding proteins, and lysozymes. In most cases the existing structural homology could be detected in a completely unbiased way. The results of the method presented are in general agreement with other studies. Applying our method, the different alignment results obtained by other authors for serine proteases and cytochromes C can be classified in terms of different alignment parameters such as gap penalties or cut-off length. Limitations of the method are discussed. PMID- 1907668 TI - FDA 'pushing envelope' on AIDS drug. PMID- 1907669 TI - A regional prospective study of in-hospital mortality associated with coronary artery bypass grafting. The Northern New England Cardiovascular Disease Study Group. AB - OBJECTIVE: A prospective regional study was conducted to determine if the observed differences in in-hospital mortality rates associated with coronary artery bypass grafting (CABG) are solely the result of differences in patient case mix. DESIGN-Regional prospective cohort study. Data including patient demographic and historical data, body surface area, cardiac catheterization results, priority of surgery, comorbidity, and status at hospital discharge were collected. This study presents data for 3055 CABG patients between July 1, 1987, and April 15, 1989. SETTING: This study includes data from all surgeons performing cardiothoracic surgery in Maine, New Hampshire, and Vermont; the data were collected from five regional medical centers. PATIENTS: Data were collected from all consecutive isolated CABG surgery patients during the study period. MAIN OUTCOME MEASURES: Crude and adjusted in-hospital mortality rates associated with CABG. MAIN RESULTS: The overall crude in-hospital mortality rate for isolated CABG was 4.3%. The rate varied among centers (range, 3.1% to 6.3%) and among surgeons (range, 1.9% to 9.2%). Predictors of in-hospital mortality included increased age, female gender, small body surface area, greater comorbidity, reoperation, poorer cardiac function as indicated by a lower ejection fraction, increased left ventricular end diastolic pressure and emergent or urgent surgery. After adjusting for the effects of potentially confounding variables, substantial and statistically significant variability was observed among medical centers (P = .021) and among surgeons (P = .025). CONCLUSION: We conclude that the observed differences in in-hospital mortality rates among institutions and among surgeons in northern New England are not solely the result of differences in case mix as described by these variables and may reflect differences in currently unknown aspects of patient care. Understanding this variation requires a detailed understanding of the processes of care. PMID- 1907670 TI - Differences in mortality from coronary artery bypass graft surgery at five teaching hospitals. AB - OBJECTIVE: To measure hospital- and surgeon-specific mortality rates for patients with coronary artery bypass graft (CABG) surgery and to examine possible reasons for any differences. DESIGN: Cohort study using hospital discharge abstracts and itemized bills. SETTING: Five major teaching hospitals in Philadelphia, Pa. PATIENTS: Consecutive sample of all 4613 patients over a 30-month period. MAIN OUTCOME MEASURE: In hospital mortality rates. RESULTS: We observed differences in hospital mortality rates for patients who underwent coronary artery catheterization and CABG surgery during the same admission (diagnosis related group 106) but not for patients who underwent only CABG surgery during the admission (diagnosis related group 107). There were threefold differences in surgeon-specific mortality rates. The hospital mortality rates for coronary artery catheterization and CABG surgery during the same admission changed during the study and coincided with moves of surgeons among study hospitals. Our measures of illness severity did identify patients who were more likely to die, but differences in severity of illness did not explain differences in hospital- or surgeon-specific mortality rates. Patient mortality rates were not associated with the volume of procedures performed by individual surgeons. We found inconclusive evidence for an association with surgeons' clinical skills, and to a lesser extent, with the hospital's volume of procedures and the hospital's organization and staffing. A greater intensity of hospital services was not necessary for a lower mortality rate. CONCLUSIONS: We conclude that studies of CABG mortality should examine mortality rates by diagnosis related group, collect data from more than 1 year, examine associations with surgeons' clinical skills, include information on hospital organization and staffing, and cautiously explore more efficient ways of providing care. PMID- 1907671 TI - Cost and benefit of secondary prophylaxis for Pneumocystis carinii pneumonia. AB - OBJECTIVE: To determine the relative cost and benefit of aerosolized pentamidine and the combination product of sulfamethoxazole and trimethoprim sulfate as secondary prophylaxis for Pneumocystis carinii pneumonia. DESIGN: A Markov-based cost-benefit analysis was performed. Drug efficacies, toxicities, and mortality rates were drawn from the current literature. SETTING: Hypothetical. PATIENT POPULATION: Patients infected with the human immunodeficiency virus who had had at least one episode of P carinii pneumonia. INTERVENTIONS: Regimen 1 required the use of aerosolized pentamidine as the sole first-line prophylactic agent in all patients. Regimen 2 required the use of sulfamethoxazole-trimethoprim in all patients who had no history of a toxic reaction to the drug; only patients with a history of toxic effects and those who developed toxic effects while receiving the drug would receive aerosolized pentamidine. Regimen 3 required that no secondary prophylaxis be given. MAIN OUTCOME MEASURES: Net cost, median patient survival, and 5-year survival for each regimen and for regimens 1 and 2 compared with regimen 3. MAIN RESULTS: Regimen 2 was dominant, with a net cost of $6332 per patient and a median survival of 2.050 years. Compared with no prophylaxis, regimen 2 resulted in a savings of $16,503 per patient and a 0.696-year increase in median survival. Compared with regimen 1, regimen 2 resulted in a savings of $2904 and a 0.067-year increase in median survival. CONCLUSIONS: Secondary prophylaxis for P carinii saves money and extends survival. Current data suggest that sulfamethoxazole-trimethoprim should be given whenever it can be tolerated. Use of aerosolized pentamidine as a first-line agent would result in a modest increase in cost and a decrease in life expectancy. PMID- 1907672 TI - Setting health care priorities in Oregon. PMID- 1907673 TI - Nutritional influence on the plasma and urine-free alkaline ribonuclease levels in severe trauma victims. AB - The significance of free alkaline ribonuclease (RNase) activity as a criterion of protein metabolism and nutrition in traumatized man is evaluated in this report. Plasma and urinary levels of RNase were measured in severely injured, hypermetabolic patients and in normal controls. Significant increases in the plasma and urinary RNase levels were seen in these polytrauma victims and they were positively correlated. Plasma RNase levels were also significantly related to blood urea nitrogen and daily urinary nitrogen excretion. Urinary clearance of RNase was increased by 220% in trauma victims, although the creatinine clearance was not affected by trauma. In a subgroup of eight patients who were fed intravenously (1.4 times basal energy expenditure calories and 250-300 mg of N per kilogram per day) for 6 days, the daily excretions of urinary RNase, nitrogen, 3-methylhistidine, creatinine, and catecholamines were measured. There was a significant negative correlation between daily urine RNase and nitrogen balance. A general increase in all the metabolic parameters on the first day of feeding was seen, suggesting a nutritional stress superimposed on the trauma induced metabolic stress. Excretion of RNase, 3-methylhistidine, and creatinine peaked on the first day of feeding and then decreased. The normal levels could not be reached even after 6 days of adequate nutrition. The results suggest that RNase levels could be used as a biomarker of protein metabolism. PMID- 1907674 TI - Effect of taurine on total parenteral nutrition-associated cholestasis. AB - A decrease in the formation/secretion of bile has been well documented in animals on total parenteral nutrition (TPN). Either an excess or an imbalance of amino acids (AA) has been most often implicated. In view of recent work showing that taurine promotes bile flow, bile acid secretion, and protects against hepatotoxic bile acids, the effect of adding taurine (15 mg/dL) to an AA solution was examined in guinea pigs on TPN for 3 days. The TPN-taurine group had a larger bile flow than the group without taurine and had bile acid secretory rates (BASR) similar to those of controls who were on saline by central catheter and had free access to food. Bile composition showed an increase in the secondary bile acid, 7 ketolithocholate and a concomitant decrease in chenodeoxycholate (CDC) in both experimental groups. Taurine led to a reversal of the usual predominance of glycine over taurine conjugated bile acids as well as to increases in HCO3 in cholesterol secretion. In response to a challenge with a large load of CDC, the TPN-taurine animals increased their BASR beyond those observed in the two other groups. These observations suggest that the addition of taurine to TPN solutions could play a role in the prevention of altered biliary function associated with AA solutions. PMID- 1907675 TI - Prospective study on the efficacy of branched-chain amino acids in septic patients. AB - The metabolic response to sepsis is characterized by increased proteolysis and gluconeogenesis, reduced protein synthesis, and negative nitrogen balance. The effects of a solution with a high proportion of branched-chain amino acids (BCAA) on the nutritional state of septic patients were evaluated. Eighty patients with peritonitis were divided into two groups of 40 patients; group 1 was administered a solution with 22.5% BCAA and group 2 with 45% BCAA. The following parameters were evaluated: anthropometrics, creatinine/height index, urinary 3 methylhistidine, nitrogen balance, stress index, albumin, prealbumin, transferrin, retinol binding protein, lymphocytes, delayed cutaneous sensitivity tests, studies of hepatic function, and plasma aminogram. In group 2 a more positive nitrogen balance, a greater drop in the stress index, a rise in plasma prealbumin and retinol binding protein levels, an increase in the creatinine/height index, and a more marked fall in the urinary excretion of 3 methylhistidine were found. When solutions with a high BCAA content were administered, there was an increase in the plasma concentrations of these amino acids in the BCAA/aromatic amino acid quotient and a decrease in the aromatic amino acids. Plasma concentrations of leucine and valine achieved very high, potentially toxic, levels at 15 days when solutions with high BCAA content were used. It is concluded that solutions with BCAA are advisable for use in the septic patient in the increased protein catabolic phase, where positive nitrogen balance, a reduction in muscle protein catabolism, and faster recovery of muscle and visceral protein were obtained. PMID- 1907676 TI - Liver dysfunction associated with long-term total parenteral nutrition in patients with massive bowel resection. AB - Sixteen patients with massive bowel resection receiving long-term home total parenteral nutrition (HTPN) for 31 to 145 months were reviewed for evidence of liver disease. Patients were divided into three groups: group 1 with duodenocolostomy (n = 3), group 2 with an estimated 15-43 cm residual small bowel (n = 7), and group 3 with an estimated 55-120 cm residual small bowel (n = 6). Two patients in group 1 developed liver cirrhosis; one was diabetic and died of sepsis and liver failure at the 88th month on HTPN; the other died of lung cancer at the 46th month on HTPN. The third patient, followed for 33 months, had transient severe liver function abnormalities associated with a blood transfusion. In groups 2 and 3, only one patient (with a history of probable liver disease before HTPN) developed biopsy-proven cirrhosis at the 60th month of HTPN. All four patients with clinically apparent liver disease developed persistent elevation of serum aspartate aminotransferase (AST) early in HTPN. Four other patients (all in group 3) with abnormal AST values in the early phase of HTPN normalized them later; they did not develop clinical liver disease over a mean follow-up time of 110 months (range, 39-152). None of the remaining eight patients (seven in group 2 and one in group 3) had significant liver function test abnormalities and none developed clinical liver disease over a mean follow up period of 72 months (range, 39-120).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1907677 TI - Energy expenditure and substrate utilization in the course of renutrition of malnourished children. AB - Energy expenditure (EE) and substrate utilization in the course of renutrition of malnourished children is not well understood in children receiving total parenteral nutrition (TPN). The aim of this study was to evaluate, during protein glucose renutrition, EE and substrate utilization and the relationship between EE and growth and/or protein metabolism. Seven malnourished children were studied during the first 3 weeks of TPN. Weight-for-height = 81.4 +/- 8.0%, with an initial weight of 4.5 +/- 3.3 kg. Caloric support was progressively increased according to a preestablished protocol. Every 7 days the following were determined: (1) EE at 3 different 3-hour intervals per day using an open circuit indirect calorimetric system, (2) anthropometrically defined fat free mass (FFM), and (3) 24-hour urinary 3-methylhistidine (3-M-His) and protein balance. Compared to initial values, EE increased 13% at day 7 and 36% at day 14. A negative relationship was found between the amount of perfused glucose and lipid utilization (r = -0.82; p less than 0.0001). EE per kilogram of total body FFM changes during renutrition were more than EE changes per kilogram of total body weight. There was a relationship between EE and weight gain (r = 0.62; p less than 0.005) and a positive relationship between EE and protein gain (r = 0.48; p = 0.012) and 3-M-His excretion (r = 0.51; p less than 0.026).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1907678 TI - Early enteral nutrition after brain injury by percutaneous endoscopic gastrojejunostomy. AB - Twenty-seven patients in a series of 52 patients with severe brain injury (Glasgow Coma Scale score less than or equal to 8) underwent insertion of intestinal feeding tubes at the bedside. The technique required endoscopy with externalization of gastric and intestinal ports through the abdominal wall. Feedings were begun through the intestinal tube with Vital HN within 4 hours of its insertion with simultaneous gastric decompression via the gastric tube. Tubes were placed 2.3 (range 0-5) days after injury. Full caloric intake (3020 kcal/24 h) was achieved by 6.8 (range 2-8) days after injury to 4.2 (range 2-8) days after placement of the feeding tube. Only 1 patient failed to tolerate feedings immediately after tube insertion. Technical inability to insert the tubes occurred in 3 patients and the intestinal tube migrated into the stomach in 2 patients; diarrhea occurred in only 1 patient. With this technique, it was possible to deliver an average daily intake of 1.2 g/kg of protein in 8-day balance periods beginning at the time of tube insertion. These data included 3- to 4-day periods in which feedings were steadily increased. In 16 patients in whom nitrogen balance was measured for 8-day balance periods, average nitrogen balance was -5.7 (range -11.3 to +3.5) g/24 h. The reduction in nitrogen loss by this technique appears equal to or superior to either gastric feeding or TPN. This technique provides the ability to enterally feed a high proportion of brain injured patients (except those in barbiturate coma) very early after injury using a bedside procedure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1907680 TI - Lack of predictive value of the APACHE II score in hypoalbuminemic patients. AB - The APACHE II score predicts mortality in severely ill patients. This score does not account for the serum albumin level. Ninety-three patients (28 with serum albumin levels less than 2.5 g/dL [group I] and 65 with serum albumin levels greater than or equal to 2.5 [group II]) were retrospectively reviewed. Patients were comparable in age, APACHE II score, and compliance with required protein needs. Patients with severe hypoalbuminemia had nearly double the death rate of patients with mildly low or normal albumin concentrations (54% compared with 29%). The death rate in the severely hypoalbuminemic patients was 5.1-fold higher than would be predicted by their APACHE II score. The death rate in those patients with mildly low or normal albumin levels had only a 1.9-fold higher rate than would be predicted by their APACHE II score. It is concluded that severe hypoalbuminemia increases the risk of death significantly higher than would be predicted by the APACHE II score. APACHE II score is not as accurate in a severely hypoalbuminemic population. PMID- 1907679 TI - Bile acid conjugation pattern in the isolated perfused rat liver during infusion of an amino acid formulation. AB - The influence of the taurine-containing amino acid mixture Trophamine on the pattern of bile acid conjugation was examined in the isolated perfused rat liver using cholic acid as the bile acid substrate. In all experiments, greater than 97% of the cholic acid appearing in bile was conjugated with taurine or glycine. The pattern of taurine and glycine bile acid conjugation, however, was dependent on the availability of taurine in the perfusate medium. Thus, in the absence of Trophamine infusion, the percentage of cholic acid conjugated with taurine (ie, taurocholate) declined throughout the course of the cholic acid infusion. Trophamine infusion increased the ratio of biliary taurocholate/glycocholate by 4.5-fold over that observed in the absence of the amino acid infusion. Increasing the amount of taurine in Trophamine by 2- or 5-fold resulted in a 1.8- and 4.3 fold increase, respectively, in the taurocholate/glycocholate ratio over that observed during the Trophamine infusion. Infusion of taurine alone, at an equimolar concentration of taurine as that in Trophamine, resulted in a similar taurocholate/glycocholate ratio as that observed during the Trophamine infusion. These data indicate that taurine availability, even in the presence of high concentrations of glycine and other amino acids in Trophamine, appears to be the most important factor in determining the pattern of bile acid conjugation in the isolated perfused rat liver. PMID- 1907681 TI - Comparative effects of an elemental and a complex enteral feeding formulation on the absorption of phenytoin suspension. AB - The effect of an elemental formula (Vivonex TEN) and a lactose-free complex formula (Ensure) on the oral absorption of a single dose of phenytoin suspension was determined in 10 normal volunteers. Following an overnight fast, subjects were randomly administered 400 mg of phenytoin suspension alone, phenytoin plus Vivonex TEN (unflavored), and phenytoin plus Ensure. The enteral feedings were given every 4 hours throughout the first 24 hours. Serum phenytoin concentrations were obtained over the 72-hour period following drug administration. No statistical difference in area under the curve (AUC), time to peak phenytoin concentration, or peak phenytoin concentration was observed during the three treatment phases. These data suggest that the two enteral feeding formulations investigated do not interfere with nor enhance or accelerate phenytoin absorption as determined by a single-dose study. PMID- 1907682 TI - Obligatory negative nitrogen balance following spinal cord injury. AB - Obligatory nitrogen losses due to paralysis in the spinal cord-injured (SCI) patient prevent positive nitrogen balance (NB) regardless of the calorie and protein intakes. Ten patients with SCI and 20 controls with nonspinal cord injury (NSCI) matched for time, sex, age, and injury severity score (ISS) were admitted to our Level I trauma center. In both groups, total nutritional support was delivered within 72 hours of admission based on predicted energy expenditures (PEE = Harris-Benedict equation x 1.2 x 1.6) and 2 g of protein/kg of ideal body weight (IBW). Subsequent changes in nutrient delivery were based on NB. No SCI patient established positive NB during the 7-week period following injury despite an average delivery of 2.4 g of protein/kg IBW and 120% of the PEE at the time of peak negative NB (-10.5). In six SCI patients, an average increase of 25% in delivered protein and 12% in delivered calories over a 1-week period effected no change in average NB (-7.4 vs -6.8). Indirect calorimetry in five SCI patients showed that calorie intakes were 110% more than average measured energy expenditures. In contrast, 17 of 20 NCSI patients achieved positive NB within 3 weeks of admission. They required an average delivery of 2.3 g of protein/kg IBW and 110% of PEE to reach positive NB. These data demonstrate the phenomenon of obligatory negative NB acutely following SCI. Aggressive attempts to achieve positive NB in these patients will fail and result in overfeeding. PMID- 1907683 TI - Home parenteral nutrition for patients with inoperable malignant bowel obstruction. AB - The use of home parenteral nutrition (HPN) in patients with inoperable malignant bowel obstruction (IMBO) is controversial. The efficacy, safety, and indications for HPN in these patients is uncertain, and its benefit is difficult to demonstrate. The records of 17 patients (9, ovarian cancer; 4, colon cancer; 4, other) with IMBO receiving HPN managed by the Nutrition Support Team (NST) at Yale-New Haven Hospital from 1980 to 1989 were reviewed. Median survival was 53 days and was longest in the two patients with appendiceal carcinomatosis (208 and 159 days), intermediate in patients with colon cancer (median 90 days), and shortest in patients with ovarian cancer (median 39 days). Survival was unrelated to age or sex. All patients died of their underlying disease; 82% of deaths occurred at home. Only one treatment-related complication requiring readmission occurred. Fourteen patients and their families (82%) perceived their therapy as highly beneficial or beneficial. The NST agreed with this assessment in 11 patients but did not share this perception in three patients. These three patients had a short duration of HPN (less than 25 days) or minimal rehabilitation. It is concluded that HPN for patients with IMBO is associated with a low complication rate, may be most beneficial for those patients with gastrointestinal tract primary tumors, and is usually perceived by patients and care providers as beneficial. HPN has palliative benefit and facilitates compassionate home care for carefully selected patients with IMBO. PMID- 1907684 TI - Clinically significant pneumatosis intestinalis with postoperative enteral feedings by needle catheter jejunostomy: an unusual complication. AB - We evaluated the incidence of clinically significant pneumatosis intestinalis and intestinal necrosis with the use of needle catheter jejunostomy in 217 consecutive patients who had undergone complicated abdominal operations or selected bariatric procedures. The needle catheter jejunostomy was used to deliver immediate postoperative nutrition, maintenance, and replacement fluids, and selected medications. In this group, no serious complications requiring surgical intervention were related to the use of needle catheter jejunostomies. Clinically significant pneumatosis intestinalis was encountered in two of 217 patients (1%). With the needle catheter jejunostomy in place, both patients improved rapidly when enteral feedings were discontinued and parenteral antibiotics were administered. None of the 217 patients developed ischemic intestinal necrosis. We conclude that 1) clinically significant pneumatosis is a rare complication of enteric feeding via needle catheter jejunostomy when the intrajejunal feeding is begun with a diluted, hypoosmolar solution with stepwise increases in osmolality, and 2) patients who do develop clinically significant pneumatosis (n = 2) seem to respond rapidly to a temporary stoppage of enteral feedings and administration of parenteral antibiotics. PMID- 1907685 TI - Osmotic diarrhea induced by sugar-free theophylline solution in critically ill patients. AB - It is widely accepted that early enteral nutrition is beneficial to critically ill patients. Diarrhea is a common problem in this setting and is often erroneously ascribed to enteral feedings. More often medications cause the diarrhea. Multiple cases of severe diarrhea associated with the use of a sugar free theophylline solution (SFTS) were discovered by a nutrition support team. SFTS may induce an osmotic diarrhea because it contains sorbitol. A 55-year-old man admitted for a dissecting aneurysm was started on isotonic formula enteral feedings and within a day of starting SFTS developed severe diarrhea. The sorbitol-induced osmotic diarrhea persisted for 36 of his 83 days of hospitalization with direct cost for the evaluation of this diarrhea being $4,250. His prolonged hospitalization cost $166,200. A retrospective review of 20 consecutive patients receiving SFTS revealed that 15 patients had diarrhea for 2 or more consecutive days compared with 20 patients receiving iv aminophylline, of whom only two patients had diarrhea. Furthermore, SFTS was administered to healthy volunteers and a prominent breath hydrogen response was noted. The polyalcohol sorbitol is used as a sweetner in "sugar-free" products and not quantified on labeling because it is considered an inactive ingredient. Nutritionists should be aware that medicinal solutions can contain enough sorbitol to create a laxative effect which is an easily reversible cause of diarrhea in enterally fed patients. PMID- 1907686 TI - Nutrition and alcoholic liver disease. AB - While the rate of malnutrition is relatively modest in alcoholic patients without alcoholic liver disease, the rate of malnutrition is virtually 100% in patients with alcoholic hepatitis and/or alcoholic cirrhosis. The reasons for malnutrition in the alcoholic hepatitis patient include various factors such as anorexia, poor diet, malabsorption, and altered metabolic state. When the patient is hospitalized, the malnutrition frequently worsens because of fasting for tests, continued anorexia, and complications such as gastrointestinal bleeding. Patients with severe acute hepatitis appear to be both hypermetabolic and hypercatabolic, whereas data are much more conflicting concerning patients with more stable liver disease. Most studies suggest that patients with alcoholic liver disease require at least 60 g of protein per day to maintain positive nitrogen balance. Consistent alterations in plasma amino acid profiles occur in alcoholic liver disease, and specialized nutritional formulations have been devised to correct this amino acid profile with the intent of improving overall nutritional status, hepatic encephalopathy, and mortality. The effects of nutritional support (including use of specialized products) on outcome, on acute hepatic encephalopathy, and on chronic or latent portal systemic encephalopathy are reviewed. PMID- 1907687 TI - Enteral feeding in the early postoperative period. PMID- 1907688 TI - Incorporating tracer-tracee differences into models to improve accuracy. AB - The ideal tracer for metabolic studies is one that behaves exactly like the tracee. Compounds labeled with isotopes come the closest to this ideal because they are chemically identical to the tracee except for the substitution of a stable or radioisotope at one or more positions. Even this substitution, however, can introduce a difference in metabolism that may be quantitatively important with regard to the development of the mathematical model used to interpret the kinetic data. The doubly labeled water method for the measurement of carbon dioxide production and hence energy expenditure in free-living subjects is a good example of how differences between the metabolism of the tracers and the tracee can influence the accuracy of the carbon dioxide production rate determined from the kinetic data. PMID- 1907689 TI - Lymphocytic interstitial pneumonia associated with a marked increase in monoclonal IgM-kappa-type rheumatoid factor and serum CA19-9. AB - A 62-year-old Japanese female was admitted due to dyspnea. She showed a marked increase in CA19-9 (maximum, 192,000 U/ml) and monoclonal IgM-kappa type rheumatoid factor (RF) activity. The patient died of respiratory failure 3 months later. Autopsy findings revealed an infiltration of IgM-kappa-positive plasma cells in the pulmonary interstitium, and therefore a diagnosis of lymphoid interstitial pneumonia (LIP) was made. The bronchoepithelial cells were stained with monoclonal antibody-reactive with CA 19-9 antigen. This is the first documented LIP, associated with a marked increase in monoclonal IgM-kappa type RF and CA19-9 in the serum. PMID- 1907690 TI - Adenosine deaminase activity and free IL-2 receptor levels in serum from patients with mycoplasma pneumonia. AB - Adenosine deaminase (ADA) activity and free interleukin (IL)-2 receptor levels were assayed in serum samples from patients with mycoplasma and bacterial pneumonia to evaluate the usefulness of these parameters in distinguishing between these diseases at an early stage. Serum ADA and free IL-2 receptor levels in patients with mycoplasma pneumonia (32.4 +/- 9.2 U/l, 960 +/- 204 U/ml) were significantly higher than those in patients with bacterial pneumonia (12.5 +/- 3.3 U/l, 425 +/- 86 U/ml) and in healthy controls (14.0 +/- 3.4 U/l, 286 +/- 49 U/ml) (p less than 0.001). Of the 20 mycoplasma pneumonia cases, 19 showed increased levels of ADA over 20.8 U/l; in 17 of the 19, the increase of ADA was seen before the elevation of the specific antibody to Mycoplasma pneumoniae. In contrast, serum ADA levels in all 20 cases of bacterial pneumonia were lower than 20.8 U/l. There results indicate that assays for serum ADA and free IL-2 receptor levels are useful in distinguishing between bacterial and mycoplasma pneumonia at an early stage. PMID- 1907691 TI - Kappa/lambda ratios of IgG, IgA and IgM in the cerebrospinal fluid of patients with Guillain-Barre syndrome. AB - The kappa/lambda (kappa/lambda) ratios of IgG, IgA and IgM in the cerebrospinal fluid (CSF) and in the sera of 10 patients with Guillain-Barre syndrome were analyzed. The kappa/lambda ratios of IgG, IgA and IgM in the CSF and in the serum were not significantly different between the acute and the late stages of Guillain-Barre syndrome nor between Guillain-Barre syndrome and the normal controls. In the CSF, however, the concentration of albumin, IgG, IgA and IgM in the acute phases of Guillain-Barre syndrome were significantly higher than in the normal controls. These results suggest that in Guillain-Barre syndrome, the increase of immunoglobulins may not be due to intrathecal synthesis and therefore there are no significant changes in the kappa/lambda ratios in the CSF. PMID- 1907692 TI - Non-Hodgkin's lymphoma accompanied by autoimmune hemolytic anemia with anti-e autoantibody. AB - A 43-year-old male with non-Hodgkin's lymphoma accompanied by autoimmune hemolytic anemia (AIHA). His blood group was group B, CcDEe. Alloantibody was absent in his serum, but autoantibody, a combination of IgG and C3d type which showed anti-e specificity, was present. Although transient improvement of AIHA was achieved by treatment with 60 mg/day of prednisolone, subsequent worsening of the anemia resulted in the patient's death. Identification of blood group specific autoantibodies may be beneficial in such a case for blood transfusion. PMID- 1907693 TI - Nephrotic syndrome associated with generalized amyloidosis and IgM-monoclonal proteinemia. AB - A 67-year-old woman was admitted for nephrotic syndrome. In spite of the lack of lymphadenopathy, hepatosplenomegaly and serum hyperviscosity, remarkable monoclonal IgM-proteinemia was demonstrated. Amyloid kidney was shown by renal biopsy. However, in the bone marrow and other organs, neither proliferation nor invasion of monoclonal immunoglobulin-producing cells was revealed by immunohistological investigations of the specimens biopsied or examined at autopsy, excluding Waldenstrom's macroglobulinemia. Immunosuppressive chemotherapy with cyclophosphamide, vincristine and prednisolone was effective in reducing serum IgM, but could not slow the progression of renal failure. This case suggested the association of generalized amyloidosis with excessive IgM proteinemia caused by a non-malignant mechanism. PMID- 1907695 TI - [Balloon occlusion pulmonary angiography and anticoagulant-antithrombotic therapy in ARDS-associated pulmonary vascular thrombosis]. AB - Balloon occlusion pulmonary angiography was used to assess the frequency of pulmonary vascular thrombosis in five patients suffering from ARDS of diverse causes. Pulmonary hypertension, elevated pulmonary vascular resistance and disseminated intravascular coagulation were observed in all patients. Pulmonary artery filling defects (PAFD) were found in four of five patients. The results suggest that PAFD can be detected in a large proportion of patients in ARDS. It was therefore speculated that the detection of PAFD is a sign of severe lung injury. Urokinase, heparin and protease inhibitor were infused to test the potential reversibility of pulmonary vascular thrombosis in four patients. After infusion, we found angiographic evidence of clearing of obstruction in arteries in three of four patients. We conclude that anticoagulant-antithrombotic therapy can improve hemodynamics in ARDS-associated pulmonary vascular thrombosis. PMID- 1907694 TI - [Interleukin-2 receptor expression in pulmonary granulomatous diseases]. AB - Interleukin-2 receptor expression (IL-2R) on monocytes and alveolar macrophages (AM) was determined in patients with sarcoidosis and pulmonary tuberculosis. In sarcoidosis and tuberculosis, IL-2R on monocytes was detectable, while it was undetectable in healthy controls. IL-2R on AM in sarcoidosis and tuberculosis was significantly increased as compared to healthy controls. IFN-gamma, which has been shown to be increased in sarcoidosis and tuberculosis as compared to healthy controls, induced IL-2R on monocytes in healthy controls, suggesting that IFN gamma is at least in part responsible for the induction or enhancement of IL-2R on monocytes or AM in sarcoidosis and tuberculosis. Phorbol myristate acetate which is known to be protein kinase C (PKC) activator induced IL-2R on monocytes, and PKC inhibitor, H7, inhibited IFN-gamma-induced IL-2R on monocytes in healthy controls. Calcium ionophore, A23187, induced IL-2R on monocytes and calmodulin antagonist, W7, inhibited IFN-gamma-induced IL-2R on monocytes. Based on these results, it seems that not only the PKC pathway but also the calcium-calmodulin pathway is involved in IFN-gamma-induced IL-2R. PMID- 1907696 TI - [Immunohistochemical analysis of granulomatous lung lesion in primary pulmonary cryptococcosis]. AB - Immunohistochemical analysis was performed in a case of pulmonary cryptococcosis that showed granulomatous pneumonia. The patient had no immunologic defects or other diseases. To cryostat sections, the immunocytes in granulomatous lesion were examined by application of monoclonal antibodies for T-lymphocytes, B lymphocyte, macrophage series cells, lymphokines containing gamma interferon (gamma IFN), interleukin 1 (IL-1) and interleukin 2 (IL-2), and interleukin 2 receptor (IL-2R). CD2+ cells, CD3+ cells and CD4+ cells were in and around the granulomas. On the other hand, CD8+ cells were around the granulomas. In granulomatous lesions, the CD4/CD8 ratio was 2.0. Some T-lymphocytes were considered as activated lymphocytes showing OKDR+, IL-2+, gamma IFN+ or IL-2R+. The lymphoid cells that aggregated near the granulomas were B-lymphocytes showing CD21+, CD24+, s-IgD+, s-IgM+, OKDR+. According to these results they were mature B lymphocytes. Alveolar macrophages (AMs) were CD11+, CD36+, IL-1+, OKDR+. Epithelioid cells were CD4+, CD11+, CD36+, OKDR+, IL-1+, IL-2R+. CD1+ cells showing dendritic forms were scattered in granulomas. They were recognized to be Langerhans giant cells. These results suggest that in pulmonary cryptococcosis the formation of epithelioid cell granulomas is mainly induced by CD4+ cells (helper/inducer T-lymphocytes). Additionally, Langerhans giant cells and mature B lymphocytes may be related to humoral immunity in pulmonary cryptococcosis. PMID- 1907697 TI - [A case of lung sarcoidosis which was clinically difficult to distinguish from hypersensitivity pneumonitis]. AB - A case of pulmonary sarcoidosis (stage III), in which the abnormal chest shadow disappeared within two weeks was reported. A 35-year-old male was admitted for further examination of bronchial asthma. He stayed overnight at home after he received inhalation provocation test of sulpyrin. Returning to the hospital, he had a fever (38 degrees C) with diffuse small nodular shadows on the chest roentgenogram. The onset and clinical features of the disease suggested hypersensitivity or drug induced pneumonitis rather than sarcoidosis. Bronchoalveolar lavage fluid (BALF) analysis showed an increase of total cell counts and lymphocytes. The surface marker of lymphocytes in BALF revealed that the CD4/8 ratio was remarkably elevated to 6.2. Both transbronchial lung and scalene node biopsy specimens revealed numerous non-caseous granulomas, and a diagnosis of sarcoidosis was confirmed. The chest infiltrates disappeared spontaneously within two weeks. This case was reported because of its rare natural course as stage III pulmonary sarcoidosis. PMID- 1907698 TI - Polymyxin B reduces cecal flora, TNF production and hepatic steatosis during total parenteral nutrition in the rat. AB - Hepatic complications are common in patients receiving total parental nutrition (TPN) and who have no underlying liver disease. In the present study we examined the hypothesis that endotoxin (LPS) or possibly TNF derived from the overgrowth of intestinal gram-negative bacteria is responsible for TPN-associated hepatic steatosis, and that bowel decontamination and specific anti-LPS activity of polymyxin B will reduce fatty infiltration of the liver during TPN. Forty-five male Sabra rats underwent jugular vein cannulation, were placed in metabolic cages, and were randomized into five groups. Group I was continuously infused with normal saline and allowed food ad lib, while group II-V were continuously infused with a TPN formula containing 4.25% amino acids and 25% dextrose for a total of 36 calories and 3.0 g protein per 100 g body weight/day. In addition, groups III-IV were also treated by oral polymyxin B while Groups IV and V received a combination of neomycin, metronidazole, and vancomycin (NMV). Thus, Group III received polymyxin B, Group IV received both polymyxin B and NMV, while Group V received NMV only. On Days 7-8 of the study, all animals were sacrificed and spontaneous production of TNF by peritoneal macrophages, bacterial translocation to mesenteric lymph nodes, culture of the cecum, and fat, triglyceride, and cholesterol contents of the liver were determined. All groups infused with TPN exhibited higher levels of total fat, triglycerides, and cholesterol compared to the free feeding control group (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1907699 TI - Diltiazem restores IL-2, IL-3, IL-6, and IFN-gamma synthesis and decreases host susceptibility to sepsis following hemorrhage. AB - Various beneficial effects of calcium channel blockers on cell and organ function following endotoxic shock, organ ischemia, and reperfusion have been reported; however, it is not known whether these agents have any salutary or deleterious effects on immune responses after low-flow conditions. Therefore, the aim of this study was to determine (a) the effect of hemorrhage on lymphocyte IL-2, IL-3, IL 6, and IFN-gamma synthesis, and (b) whether diltiazem has any salutary or adverse effects on these parameters when administered following hemorrhage and resuscitation. To study this, C3H/HeN mice were bled to a mean blood pressure of 35 mm Hg, maintained at that level for 60 min, and resuscitated with shed blood plus twice that volume of Ringer's lactate. Immediately following resuscitation mice received either diltiazem (2400, 800, or 400 micrograms/kg body wt), or an equivalent volume of saline. The mice were sacrificed 24 hr later, splenic lymphocytes were obtained, and their capacity to produce lymphokines was assessed. The results indicated that in the vehicle-treated animals, hemorrhage significantly decreased (P less than 0.05) IL-2, IL-3, IL-6, and IFN-gamma synthesis by 82 +/- 19%, 64 +/- 28%, 71 +/- 11%, and 86 +/- 14%, respectively. However, diltiazem (400 but not 2400 micrograms/kg) treatment after hemorrhage restored lymphocyte capacity to produce IL-2, IL-3, IL-6, and IFN-gamma (P less than 0.05). Additional groups of animals were subjected to sepsis by cecal ligation and puncture 3 days following hemorrhage.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1907701 TI - [Unclear statement for measurement of glomerular filtration]. PMID- 1907700 TI - Valve extension with glutaraldehyde-preserved autologous pericardium. Results in mitral valve repair. AB - Preliminary experimental studies in our laboratory have shown that autologous pericardium treated with glutaraldehyde prevents late deterioration and calcification of the tissue. For this reason, glutaraldehyde-treated autologous pericardium has been used in a series of 64 patients who underwent operations for leaflet extension of the mitral valve between 1980 and 1989. Ages ranged from 2.5 to 60 years (mean 19 +/- 15). The causes of mitral valve insufficiency were rheumatic fever (69%), bacterial endocarditis (17%), congenital (8%), endomyocardial fibrosis (4.5%), and trauma (1.5%). The autologous tissue was fixed in a 0.62% glutaraldehyde solution for 15 minutes and rinsed in saline for an additional 15 minutes. Patching techniques varied depending on the site and the extent of the lesion. Associated mitral valve repair techniques (Carpentier's techniques) were mandatory in all patients. The period of follow-up extended from 6 months to 9 years (mean 3.1 +/- 2.5 years). There were no operative deaths in this series, and there was one late death (2%). In the six patients (12%) who underwent reoperation, there has been no case of calcification of the pericardial patch. Postoperative mitral valve function was assessed by bidimensional color Doppler echocardiographic techniques. Mitral valve insufficiency was trivial or absent in 80% of the patients. This experience permits us to conclude that leaflet extension is a simple and safe technique in valve reconstruction, allowing repair of mitral valves that otherwise would need to be replaced. It permits use of an adult-size prosthetic ring in children. Glutaraldehyde-treated autologous pericardium is the material of choice for this type of repair. PMID- 1907702 TI - [Time for an efficiency assessment system for patients with schizophrenia]. PMID- 1907703 TI - [Too little health care for invested money. Estimation of costs of coronary angiography]. PMID- 1907704 TI - Effects of interleukin-1 beta on secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) by cultured rat anterior pituitary cells. AB - Interleukin-1 beta (IL-1 beta) at doses of 0.15 and 1.5 nM significantly inhibited FSH secretion and stimulated LH secretion by cultured rat pituitary cells after 24-72 hr incubation whereas 15 pM of IL-1 beta was not effective. Treatment with IL-1 beta for 12-48 hr did not affect intracellular content of FSH. However, treatment with 0.15 and 1.5 nM of IL-1 beta for 72 hr significantly suppressed intracellular content of FSH whereas various doses of IL-1 beta incubated with the cells for 12-72 hr showed no effect on the intracellular content of LH. Pretreatment with IL-1 beta for 48 hr inhibited both GnRH-mediated LH and FSH secretions by the pituitary. The secretion of FSH and LH mediated by an activator of protein kinase C, phorbol 12-myristate 13-acetate, was also significantly suppressed by pretreatment with IL-1 beta for 48 hr. These results suggest that (a) IL-1 beta has opposite effects on the secretion of LH and FSH and (b) pretreatment with IL-1 beta suppresses GnRH-mediated stimulation of LH and FSH by the pituitary and this suppressive effect of IL-1 beta may involve the suppression of a protein kinase C-dependent mechanism. PMID- 1907705 TI - The role of polyols in cerebral cell volume regulation in hypernatremic and hyponatremic states. AB - To clarify the role of the sugar polyols, sorbitol and myo-inositol, in cerebral cell volume regulation, we studied the effect of sorbinil, an inhibitor of aldose and aldehyde reductase, on the size of the cerebral water compartments in rats with hypernatremia, hyponatremia and normonatremia. Experimental animals were pretreated with sorbinil, while comparison rats received the drug vehicle. Rats were made hypernatremic for 96 h by water deprivation and injections of hypertonic saline, while hyponatremia was provoked over 48 h by daily administration of 5% dextrose in water and vasopressin. Sorbinil treatment was continued throughout the hyper- and hyponatremic periods. The severity of hypernatremia and hyponatremia was similar in sorbinil-treated and corresponding vehicle-treated rats. Brain electrolyte content and the size of the cerebral intracellular water compartment were comparable in sorbinil-treated rats vs. controls under hypernatremic and hyponatremic conditions. Sorbinil reduced the cerebral sorbitol content by approximately 50%, irrespective of the serum Na+ concentration. In contrast, sorbinil had no effect on brain myo-inositol content which rose by 114% during chronic hypernatremia (P less than 0.0001). Cerebral levels of myo-inositol did not decline in hyponatremic rats. We conclude that (1) sorbitol is not an essential cerebral osmolyte; and (2) myo-inositol is involved in the maintenance of brain cell volume during severe hypernatremia but not under hyponatremic conditions. PMID- 1907707 TI - Methyl-branched octanoic acids as substrates for lipase-catalyzed reactions. AB - Hydrolyses of racemic methyl-branched octanoic acid thiolesters are described using six commercial lipases as catalysts. Branching at positions 2, 4 and 5 greatly reduced activity; branching at the 3-position virtually eliminated activity. The reactivities of the racemic branched thiolesters relative to the unbranched ester were very similar for each lipase preparation examined. In reactions involving configurationally pure 2-methyloctanoic acids, the S enantiomer reacted faster both in esterification of aliphatic alcohols and in hydrolyses of aliphatic alcohol esters with all of the lipases examined. Stereobiases in hydrolyses of the octanoic acid esters branched at other positions were low and variable. In sharp contrast to the hydrolyses of the thiolesters of 2-methyloctanoic acid, two aryl esters of 2-methyloctanoic acid catalyzed by R. miehei lipase hydrolyzed with a bias for the R-configuration. A view of the ester-enzyme complex is offered to explain the relative rates of reaction of the racemic esters. PMID- 1907706 TI - The effect of dietary n-3 polyunsaturated fatty acids on HDL cholesterol in Chukot residents vs muscovites. AB - Native Chukot Peninsula residents, in contrast to Muscovites, consume a diet rich in n-3 polyunsaturated fatty acids. This dietary peculiarity is reflected in differences in plasma lipid and apolipoprotein contents. The Chukot residents have lower contents of total cholesterol, triglyceride, LDL (low density lipoprotein) cholesterol and apolipoprotein B, but higher HDL (high density lipoprotein) cholesterol levels than do Muscovites. The apolipoprotein A-I levels were identical in both groups. A higher HDL cholesterol to apolipoprotein A-I ratio was determined in the coastline Chukot residents (0.52 +/- 0.01) than in Muscovites (0.43 +/- 0.01; p less than 0.01). In contrast to Muscovites, the coastline Chukot residents also had higher n-3 and lower n-6 polyunsaturated fatty acid percentages in plasma and erythrocyte lipids, and lower phosphatidylcholine and higher sphingomyelin or phosphatidylethanolamine levels in HDL2b and HDL3. The higher HDL cholesterol levels in the plasma of the coastline Chukot residents appears to reflect the higher cholesterol-scavenging capacity of their HDL. We conclude from this study that the regular consumption of dietary n-3 polyunsaturated fatty acids by the coastline Chukot residents decreased LDL cholesterol transfer from plasma to peripheral cells, and enhanced cholesterol efflux from cellular membranes toward HDL. PMID- 1907708 TI - The use of a Markov process to simulate and assess follow-up policies for patients with malignant disease: surveillance for stage I nonseminomatous tumors of the testis. AB - Using a Markov process to simulate and assess surveillance policies for stage I nonseminomatous germ cell tumors, the authors analyzed costs and effectiveness for the various policies that have been used clinically. They found no real differences in effectiveness, defined as probability of surviving two years, between the policies. There were significant differences in costs. The model is used to suggest schedules that might be more cost-effective than those currently employed. The model suggests that computed tomographic scanning of the abdomen may not be essential to the effectiveness of surveillance protocols. PMID- 1907709 TI - Cost-effectiveness concepts and the CE plane. PMID- 1907710 TI - The efficacy of diagnostic imaging. AB - The authors discuss the assessment of the contribution of diagnostic imaging to the patient management process. A hierarchical model of efficacy is presented as an organizing structure for appraisal of the literature on efficacy of imaging. Demonstration of efficacy at each lower level in this hierarchy is logically necessary, but not sufficient, to assure efficacy at higher levels. Level 1 concerns technical quality of the images; Level 2 addresses diagnostic accuracy, sensitivity, and specificity associated with interpretation of the images. Next, Level 3 focuses on whether the information produces change in the referring physician's diagnostic thinking. Such a change is a logical prerequisite for Level 4 efficacy, which concerns effect on the patient management plan. Level 5 efficacy studies measure (or compute) effect of the information on patient outcomes. Finally, at Level 6, analyses examine societal costs and benefits of a diagnostic imaging technology. The pioneering contributions of Dr. Lee B. Lusted in the study of diagnostic imaging efficacy are highlighted. PMID- 1907712 TI - Glucose-alanine relationship in diabetes in human pregnancy. AB - We have previously reported a decrease in gluconeogenesis from alanine in normal pregnant women at term gestation as compared with nonpregnant women. In the present study, the effect of diabetes on alanine metabolism was examined in five gestationally diabetic (GDM) women and seven women with type I (insulin dependent) diabetes (IDDM) during the third trimester of pregnancy. The hemoglobin A1c (HbA1c) concentrations in all subjects were within normal range, indicating good metabolic control. After an overnight fast, each subject was infused simultaneously with L-[2,3, 13C2]alanine and D-[6,6,2H2]glucose tracers as prime constant rate infusion. Plasma alanine and glucose isotopic enrichments were measured by gas chromatography-mass spectrometry. Alanine and glucose turnover rates were quantified by tracer dilution. In five subjects, the contribution of alanine carbon to CO2 was quantified by respiratory calorimetry and by measurement of 13C enrichment of expired CO2. Data from 15 previously reported normal pregnant subjects were used for comparison. The rate of alanine turnover was similar in the GDM and IDDM subjects and was not different from the normal subjects (GDM, 4.6 +/- 1.9; IDDM, 5.4 +/- 2.5; normals, 4.4 +/- 0.8 mumol/kg.min, mean +/- SD). The rate of glucose turnover was significantly reduced (P less than .05) in IDDM as compared with GDM and normal subjects (IDDM, 8.1 +/- 0.8; GDM, 11.5 +/- 3.5; normals, 12.2 +/- 2.2 mumol/kg.min). The contribution of alanine C to glucose C and expired CO2 was similar in the three groups. These data demonstrate that rigorous metabolic control results in normal glucose and alanine metabolism in diabetic pregnancy during fasting.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1907711 TI - Comparative effects of omega-3 and omega-6 polyunsaturated fatty acids on protein metabolism in rats bearing the mammary adenocarcinoma. AB - The comparative effects of diets containing 20% (wt/wt) of either fish oil (FO) or safflower oil (SO) on protein synthesis and catabolism were determined in rats bearing the 7,12-dimethylbenz(a)anthracene (DMBA) 13762 mammary adenocarcinoma in vivo using a 6-hour constant infusion of L-(1-14C)-leucine. Tumor-bearing animals fed FO had significantly lower tumor growth rate (36 +/- 0.5 v 53 +/- 0.7%/d, P less than .05), total tumor protein synthesis (Ts) (1.25 +/- 0.1 v 1.85 +/- 0.1 mumol/h, P less than .05), and tumor protein concentration (12.0 +/- 0.5 v 14.0 +/- 0.7%/d, P less than 0.01). Tumor fractional synthetic rate and total protein breakdown rate of the tumor were unaffected by FO feeding. Both tumor-bearing and saline-control animals fed FO had significantly (P less than .01) lower liver fractional synthetic rate and total protein breakdown rate, and higher liver total protein compared with SO-fed rats. Muscle protein kinetics were unaffected by either treatment or diet. Whole body protein kinetics were not affected by dietary treatment, but the presence of tumor significantly (P less than .001) reduced whole body flux, synthesis, breakdown, and oxidation. Chronic FO feeding for 7 weeks significantly (P less than .001) lowered omega-6 polyunsaturated fatty acids (omega-6 PUFAs) and significantly elevated omega-3 polyunsaturated fatty acids (omega-3 PUFAs) (P less than .001) in both plasma phospholipid and triglycerides. The present study indicates that dietary FO can modulate mammary tumor growth in a manner that reflects changes in protein metabolism in both host and tumor tissues. PMID- 1907713 TI - Microbial lipids and stable foam formation in the activated sludge process. AB - The presence of fats and oils in sewage has been related to the formation of stable foams in activated sludge treatment systems. Foam forming microbes can utilise and, in some cases, store lipid substrates. Since surface lipids would confer the hydrophobicity necessary for flotation on the sludge biomass, the extractable lipids in foaming and non-foaming biomass samples were examined. Both pure mono-cultures and sludge samples were used. The results showed that, whilst there were some differences in the lipid profiles of the mono-cultures, the different sludge types did not show any significant pattern or variation which could be used as a lipid-based explanation for foam formation. PMID- 1907714 TI - Pseudomonas aeruginosa resistant to aminoglycosides: an assessment of the currently used methods of disk diffusion and dilution susceptibility. AB - In recent years, a number of clinical microbiology laboratories have isolated Pseudomonas aeruginosa with the unusual aminoglycoside disk diffusion result of resistance to both amikacin and gentamicin but susceptibility to tobramycin (ArGrTs). A total of 27 isolates of P. aeruginosa reported to have this resistance pattern was retested by the standard National Committee for Clinical Laboratory Standards disk diffusion procedure; twenty strains (74%) were confirmed to be ArGrTs. These twenty isolates were further examined for susceptibility to those aminoglycosides by agar dilution and both micro- and macrodilution methods. Only 25, 25 and 24% of the isolates appeared to be ArGrTs by agar, broth microdilution, and broth macrodilution testing respectively. Most of the remaining isolates were resistant to all three aminoglycosides when tested by broth dilution and resistant only to gentamicin when tested by agar dilution. The percentages of strains resistant to any particular aminoglycoside by agar dilution, broth microdilution and broth macrodilution, respectively were 44, 79 and 69 for amikacin, 95, 91 and 100 for gentamicin, 100, 100 and 100 for netilmicin, 28, 85 and 91 for sisomicin, and 11, 54 and 46 for tobramycin. These results indicate that strains showing the unusual aminoglycoside antibiogram are less susceptible to aminoglycosides in general and should probably be considered borderline resistant to all aminoglycosides. The efficacy of aminoglycosides in the treatment of infections produced by these strains is unknown. PMID- 1907715 TI - Kinetics of the extracellular proteinase production by the proteolytic biovar of Enterococcus faecalis in complex media and skim milk. PMID- 1907716 TI - Kinetic maturation of an immune response. AB - Is the affinity maturation of antibodies under thermodynamic or kinetic control, or both? We compared the physical constants of hapten binding by antibodies from 2-phenyl-5-oxazolone-specific hybridomas from primary, secondary and tertiary responses. In addition to an increase in equilibrium constant, there was a shift in the antibody repertoire after the primary response towards an immunoglobulin family with an extremely high on-rate constant. This shift occurred in spite of the average or below-average affinity of this group of antibodies. This is consistent with B-lymphocyte proliferation being subject to a kinetic selection, with a premium on binding target antigens rapidly, in parallel with a thermodynamic selection based on binding tightly. PMID- 1907717 TI - Release factors and the genetic code. PMID- 1907718 TI - Making antibody fragments using phage display libraries. AB - To by-pass hybridoma technology and animal immunization, we are trying to build antibodies in bacteria by mimicking features of immune selection. Recently we used fd phage to display antibody fragments fused to a minor coat protein, allowing enrichment of phage with antigen. Using a random combinatorial library of the rearranged heavy (VH) and kappa (V kappa) light chains from mice immune to the hapten 2-phenyloxazol-5-one (phOx), we have now displayed diverse libraries of antibody fragments on the surface of fd phage. After a single pass over a hapten affinity column, fd phage with a range of phOx binding activities were detected, at least one with high affinity (dissociation constant, Kd = 10(-8) M). A second pass enriched for the strong binders at the expense of the weak. The binders were encoded by V genes similar to those found in anti-phOx hybridomas but in promiscuous combinations (where the same V gene is found with several different partners). By combining a promiscuous VH or V kappa gene with diverse repertoires of partners to create hierarchical libraries, we elicited many more pairings with strong binding activities. Phage display offers new ways of making antibodies from V-gene libraries, altering V-domain pairings and selecting for antibodies with good affinities. PMID- 1907719 TI - Transformation suppressor activity of a Jun transcription factor lacking its activation domain. AB - The oncoprotein c-Jun is thought to be a mediator of ras transformation as both its synthesis and activity as a transcription factor are stimulated by ras expression. But c-Jun co-operates with ras in transformation assays, suggesting that they act along different pathways (reviewed in ref. 4). Here we show by means of a dominant-negative mutated transcription factor that c-Jun potentially in conjunction with other factors that interact with it is necessary for transformation by ras. The mutant Jun lacks an activation domain and blocks stimulation of transcription by several oncoproteins, including Ras, v-Src, polyoma middle T, c-Jun and c-Fos, as well as by the tumour promoter 12-O tetradecanoylphorbol-13-acetate (TPA). The inhibition is specific for motifs that bind Jun: activation of an NF-kappa B/Rel motif is not affected. This Jun mutant acts as an anti-oncogene in ras-transformed cells, generating non-transformed revertants that have acquired anchorage and density-dependent growth, as well as reduced tumorigenicity in vivo. Mutants of other transcription factors designed to inhibit transformation will enable us to study their role in signal transduction. PMID- 1907720 TI - Adenosine receptors mediate a pertussis toxin-insensitive prejunctional inhibition of noradrenaline release on a papillary muscle model. AB - The effects of adenosine receptor agonists and antagonists on field-stimulated release of radioactivity from superfused guinea-pig papillary muscles preincubated with [3H] noradrenaline were studied. N6-cyclopentyladenosine (CPA), N6-(R-phenylisopropyl)-adenosine, and 5'-N-ethylcarboxamidoadenosine caused concentration-dependent inhibition of evoked overflow with a rank order of potency typical for interaction of the compounds with the A1-subtype of adenosine receptors. Maximum inhibition was 80%. The A1-selective antagonist 8-cyclopentyl 1,3-dipropyl-xanthine (DPCPX) induced a rightward shift of the concentration response curve for CPA with a pA2 of 8.35. However, DPCPX per se had no effect on stimulation-evoked tritium overflow. On the other hand, in the presence of 4 nitrobenzylthioinosine (2 mumol/l) and deoxycoformycin (1 mumol/l), inhibitors of adenosine uptake and deamination, respectively, DPCPX produced a concentration dependent increase in overflow with a pD2 of 8.1. Pretreatment of the animals with pertussis toxin caused a substantial reduction in the activity of toxin sensitive G proteins, as indicated by a lack of [32P]ADP ribosylation in a ventricular membrane preparation. Nevertheless, the inhibitory effect of the adenosine receptor agonists on stimulus-evoked overflow remained unaffected. These results are compatible with the existence of inhibitory prejunctional adenosine receptors in guinea-pig papillary muscle, which appear to be coupled to a pertussis toxin-insensitive G protein. The role of endogenous adenosine in occupying these receptors seems minimal under basal conditions. PMID- 1907721 TI - [Benefit of the serological screening program for syphilis in pregnant women in Amsterdam in the period 1985-1989]. AB - The results of the serological syphilis screening programme for pregnant women in the region of Amsterdam in the period 1985-1989 are described. In addition, a cost-benefit analysis was done to determine useful effects of the programme. Every GP and obstetrician routinely takes blood samples from pregnant women to determine the blood group, rhesus factor and syphilis serology. In the period 1985-1989, a total of 37,520 serum samples were screened for syphilis in the Amsterdam region by the Central Laboratory of the Blood Transfusion Service (until mid-1986) and by the Regional Public Health Laboratory of the Municipal Health Service (from mid-1986). In 55 women (0.15%) both the Treponema pallidum haemagglutination assay (TPHA) and the venereal disease research laboratory (VDRL) tests were positive. Further evaluation of these 55 women ultimately brought to light 10 women with positive syphilis serology who had not been treated and consequently might infect their child with Treponema pallidum. Considering the various transmission percentages of the bacterium from mother to foetus, which depend on the stage of the maternal infection, the screening programme has prevented two cases of congenital syphilis. This brings the cost benefit ratio of the syphilis screening programme for the region of Amsterdam to 1:6.2. In view of these findings there is no reason to reconsider the current screening practice in Amsterdam. PMID- 1907722 TI - [Polychlorobiphenyls in human milk, adipose tissue, plasma and umbilical cord blood; levels and correlates]. AB - In a longitudinal study involving 17 women, PCB concentrations (PCBs 138, 153 and 180) were determined in cord blood (17 newborns), breast milk (10 women), maternal adipose tissue (8 women), maternal plasma collected during the last trimester of pregnancy (17 women) and maternal plasma collected 10 days post partum (7 women). Significant correlations were found (p less than 0.05) between PCB levels in cord blood, breast milk and adipose tissue and maternal plasma collected before birth, and between breast milk and maternal plasma collected post partum. In 2 vegetarian women the PCB levels in maternal plasma and cord blood were significantly lower than in the other women (p less than 0.05). If in future studies the PCB levels observed prove to be detrimental to child development, these correlations may offer the possibility of identifying a group of newborns at risk for occurrence of developmental defects due to PCB exposure before birth. PMID- 1907723 TI - Effects of inhibition of monoamine oxidase on the levels of 5-S-cysteinyl adducts of catechols in dopaminergic regions of the brain of the guinea pig. AB - The occurrence of 5-S-cysteinyl adducts of dopamine (DA), 3,4 dihydroxyphenylacetic acid (DOPAC) and 3,4-dihydroxyphenylalanine (DOPA) in brain tissue, appears to reflect in vivo autoxidation of DA, DOPA and DOPAC, respectively. In the striatum and in the limbic system of guinea pig, the levels of DOPAC and 5-S-cysteinyl-DOPAC were markedly reduced after treatment with pargyline (75 mg/kg, i.p., 17 hr) and pargyline plus reserpine (75 mg/kg, i.p., 17 hr plus 5 mg/kg, i.p., 18 hr) compared to controls. However, the depletion of 5-S-cysteinyl adduct was less severe than that of DOPAC, suggesting a slower turnover of the adduct. Dopamine and 5-S-cysteinyl-DA increased significantly and to the same extent in the striatum, after pargyline alone. In the limbic system DA was significantly increased, whereas no change was found for levels of 5-S cysteinyl-DA. 5-S-Cysteinyl-DOPA decreased significantly in the striatum after treatment with pargyline plus reserpine and non-significantly after pargyline alone. The data are compatible with a slight inhibitory effect of MAO inhibition on catechol autoxidation. This effect was, however, overridden by the increased level of DA. PMID- 1907724 TI - [Central venous catheterization via exposure of the axillary vein in long-term total parenteral nutrition. Technical notes]. PMID- 1907725 TI - Rhabdomyolysis associated with lithium-induced hyperosmolal state. PMID- 1907726 TI - Inhibition of pertussis toxin catalyzed ADP-ribosylation of G-proteins by membrane depolarization in rat brain synaptoneurosomes. AB - Rat brainstem synaptoneurosomes at resting and depolarization potentials were subjected to ADP-ribosylation in the presence of pertussis toxin (PTX). Subsequent [32P]ADP-ribosylation of synaptoneurosomal membranes revealed labeling of a 39-kDa protein band which reacted with antibodies to the alpha-subunit of G proteins, mainly Go. ADP-ribosylation of the G-proteins was completely achieved in synaptoneurosomes at resting potential ( [K+] = 4.7 mM). In the depolarized synaptoneurosomes, however, the higher the membrane potential the lower the extent of ADP-ribosylation achieved (46% and 11% in K+ concentrations of 50 and 100 mM, respectively). A similar effect of membrane depolarization on PTX catalyzed ADP-ribosylation was expressed in the functional coupling between G protein activation and changes induced in the muscarinic receptor affinity. These findings may indicate a depolarization-induced inhibition of PTX-catalyzed ADP ribosylation of G-proteins. PMID- 1907727 TI - Protein analysis of Theileria sergenti/buffeli/orientalis piroplasms by two dimensional polyacrylamide gel electrophoresis. AB - Proteins of the piroplasms of Theileria sergenti, T. buffeli and T. orientalis were analysed by two-dimensional polyacrylamide gel electrophoresis. Protein spot patterns of T. buffeli and T. orientalis were identical except for a few minor proteins, whereas spot patterns of two T. sergenti stocks were differentiated from those of T. buffeli and T. orientalis by a characteristic set of proteins including a major protein of molecular weight 33-34 kDa. This result indicates that Japanese T. sergenti can be phenotypically distinguishable from European and Australia Theileria species; T. orientalis and T. buffeli. PMID- 1907728 TI - Theileria parva: influence of vector, parasite and host relationships on the epidemiology of theileriosis in southern Africa. AB - The protozoan parasite Theileria parva, transmitted by the ixodid tick Rhipicephalus appendiculatus, is the cause of East Coast fever (ECF) and the related syndromes of Corridor disease and January disease in cattle of eastern, central and southern Africa. It is likely that buffalo (syncerus caffer) are the natural host of T. parva. In eastern and southern Africa, there exists both buffalo-adapted and cattle-adapted T. parva. Disease caused by buffalo-adapted parasites is called Corridor disease, and that caused by cattle-adapted parasites is termed East Coast fever. In eastern Africa, it has been shown experimentally that buffalo-adapted T. parva can, after serial passage in cattle, become adapted to cattle, in which it can then be maintained and cause ECF. This adaptation has been termed transformation. The transformation of buffalo-adapted T. parva to a cattle-adapted parasite has not been reported in southern Africa, and ECF, eradicated from South Africa, Swaziland and southern Mozambique by 1960, has not reappeared in the subcontinent. This paper discusses the possible reasons for this, and hypothesizes that vector population dynamics and the susceptibility of the vector population to infection with T. parva are among the most important factors which influence the expression of ECF as a disease entity, and the likelihood of transformation occurring. It also considers the possibility that disappearance of ECF from southern Africa resulted from the extinction, as a result of vigorous control measures and unfavourable climatic conditions, of non diapausing populations of R. appendiculatus that may have been introduced from eastern Africa with cattle imported in 1901. PMID- 1907729 TI - Bloodstream Trypanosoma cruzi parasites from mice simultaneously express antigens that are markers of acute and chronic human Chagas disease. AB - Several recombinant Trypanosoma cruzi proteins previously isolated were used as antigens to analyse antibody specificities present in sera from human infections. Some parasite proteins such as SAPA (Shed Acute Phase Antigen) are antigenic early after infection. Others, like antigens 1 and 30, are antigenic mainly during the chronic phase of the infection. To understand why different proteins are antigenic at different periods of infection, specificities of antibodies present in the sera of infected mice were compared with the antigens expressed by parasites collected directly from blood. Parasites collected during the acute parasitaemia peak expressed not only antigen SAPA, but also antigens 1 and 30. However, only antibodies against SAPA were frequently observed during the early period and also in the chronic phase of murine infection. Long-lasting antibodies against SAPA were detected regardless of the mouse and parasite strains used. Furthermore, all 8 recombinant clones detected in a T. cruzi expression library with pooled sera from acutely infected mice were homologous to the SAPA gene. These results show that even though parasites from the acute parasitaemia peak in mice may express simultaneously several proteins known to be antigenic, only antibodies against SAPA were consistently detected. PMID- 1907730 TI - Response of cerebral blood volume to changes in arterial carbon dioxide tension in preterm and term infants. AB - The response of cerebral blood volume (CBVR) to a small induced change in arterial carbon dioxide tension was studied by near-infrared spectroscopy in 17 newborn infants born from 26 wk of gestation to term. All 17 infants were undergoing mechanical ventilation but had apparently normal brains. The CBVR per kPa change in arterial carbon dioxide tension within the range 3.9 to 9.6 kPa was calculated from the change in total cerebral Hb concentration ([TCHb]) using the equation: delta CBV = delta [TCHb] x 0.89/[H] where [H] is the large vessel Hb concentration. A least-squares regression line with 95% confidence limits was derived for CBVR against gestational age. A highly significant linear increase in CBVR was found: mean CBVR from the regression increased from 0.07 mL.100 g-1.kPa 1 at 26 wk to 0.51 mL.100 g-1.kPa-1 at 40 wk. PMID- 1907732 TI - Management--input to outcome. PMID- 1907731 TI - Refeeding enhances intestinal repair during an acute enteritis in infant rabbits subjected to protein-energy malnutrition. AB - We examined the effects of refeeding during an acute bacterial enteritis on small intestinal repair in infant rabbits subjected to protein-energy malnutrition and in noninfected and infected dietary controls. Malnutrition was induced by litter expansion at 7 d of age. Randomly selected litters from both dietary groups were infected on d 17 with Yersinia enterocolotica. Inflammation and intestinal damage were observed in the jejunum and ileum at the "acute stage" of infection in 23-d old animals from both dietary groups, as evidenced by an inflammatory infiltrate, blunted villi, and reduced disaccharidase activities. In addition, ileal glucose stimulated Na+ absorption was depressed. On d 24, a 7-d period of ad libitum refeeding of breast milk and rabbit feed was initiated in randomly selected litters of infected-malnourished animals and all dietary controls. Mucosal repair was nearly complete at 31 d of age in infected dietary controls and in the infected-malnourished animals that were refed, as demonstrated by the recovery of segmental mucosal mass and ileal glucose-stimulated Na+ transport in association with the resolution of inflammation and diarrhea. Only mucosal disaccharidase activities remain depressed. In contrast, in 31-d-old infected-malnourished animals subjected to ongoing nutrient deprivation, severe intestinal damage persisted as evidenced by increased mortality, ongoing intestinal inflammation, mucosal hypoplasia, depressed disaccharidase activities, and reduced glucose stimulated Na+ transport. We conclude that a refeeding regimen introduced during an acute bacterial enteritis is well tolerated and promotes recovery of intestinal mass, structure, and function in malnourished infant rabbits and dietary controls. PMID- 1907733 TI - Inhibition of mouse skin tumor-initiating activity of DMBA by chronic oral feeding of glycyrrhizin in drinking water. AB - Licorice (Glycyrrhiza glabra), a Mediterranean plant, has been used as an antidote, demulcent, and elixir folk medicine for generations in China. The main water-soluble constituent of licorice is glycyrrhizin (GL), which has been shown to possess several pharmacological properties. In this study, we show that oral feeding of GL to Sencar mice resulted in substantial protection against skin tumorigenesis caused by 7,12-dimethyl-benz [a]anthracene (DMBA) initiation and 12 O-tetradecanoylphorbol-13-acetate (TPA) promotion. The latent period prior to the onset of tumor development was considerably prolonged in GL-fed animals compared with animals not fed GL and resulted in significant decrease in the number of tumors per mouse, during and at the termination of the experiment. Oral feeding of GL in drinking water also resulted in inhibition in the binding of topically applied [3H]benzo[a]pyrene and [3H]DMBA to epidermal DNA. The possible mechanism(s) of the antitumor-initiating activity may be due to the involvement of GL as inhibitor of the carcinogen metabolism followed by DNA adduct formation. Our results suggest that GL possesses considerable antitumorigenic activity and could prove useful in protecting some forms of human cancer. PMID- 1907734 TI - Effect of dietary kelp on lipid peroxidation and glutathione peroxidase activity in livers of rats given breast carcinogen DMBA. AB - In our previous study of female rats, a diet containing 2% of powdered fronds of Laminaria religiosa (kelp) had a remarkable inhibitory effect on mammary tumorigenesis induced by orally given 7,12-dimethylbenz[a]anthracene (DMBA). In this study, the effect of the dietary kelp on lipid peroxidation and glutathione peroxidase (GSH-Px) activity in the liver was studied in the same experimental system. Two separate short- and long-term experiments were carried out on rats fed a diet with 2% kelp. DMBA (20 mg/kg body wt) was given to each animal 7 days after feeding began in short-term experiment and 27 days later in long-term experiment. Livers of all rats were obtained for quantitative determination and for histopathologic observation. Lipoperoxide in livers of the kelp-fed rats was of normal value, almost the same as that of untreated control rats; however, lipoperoxide in livers of control rats was significantly higher than in the other two groups in both experiments. A marked fatty change in livers of control rats was demonstrated in hepatic cells in peripheral zones of lobules in long-term experiment but not in short-term experiment. In long-term experiment, the amounts of GSH-Px and selenium in livers of kelp-fed rats were slightly less than those in untreated control rats but more than those in control rats. There was a more intense positive reaction in the hepatic cells in the peripheral zones of the lobules in the kelp-fed and untreated rats and a less-intense positive reaction in control rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1907736 TI - Different effects of paraquat on microsomal lipid peroxidation in mouse brain, lung and liver. AB - Paraquat stimulates NADPH-Fe(2+)-dependent microsomal lipid peroxidation in mouse brain and strongly inhibits it in the liver. In lung microsomes, the lipid peroxidation was stimulated by paraquat at 10(-4) M, but not at higher doses. An antioxidant action of paraquat seemed to account, at least in part, for the lack of stimulation in lung microsomes, but it was inappropriate to explain the result in hepatic microsomes. There was no apparent correlation between the effects of paraquat on the lipid peroxidation and on the activity of NADPH-cytochrome P-450 reductase, the enzyme which initiates redox cycling of paraquat, resulting in generation of active oxygen species. In fact, the effect of paraquat on the lipid peroxidation was independent of paraquat radical production, an intermediate in the cycle. However, the inhibitory potency of N-ethylmaleimide on NADPH cytochrome P-450 reductase activity paralleled that on the lipid peroxidation stimulated by paraquat in brain and lung. These findings indicate that the effect of paraquat on microsomal lipid peroxidation differs among the organs and that other factors, besides NADPH-cytochrome P-450 reductase, might be involved in the stimulation of lipid peroxidation by paraquat. PMID- 1907735 TI - Sustained pharmacological activities in rats following single and repeated administration of once-a-month injectable microspheres of leuprolide acetate. AB - Once-a-month injectable microspheres of leuprolide acetate prepared with copoly(DL-lactic/glycolic acid) using an in-water drying method were assessed for duration of the analogue release and pharmacological effects in rats after a single or repeated injection. The periodic challenge test revealed that a single injection of the microspheres caused a dramatic and persistent suppression of the ability of the pituitary-gonadal system to secrete gonadotropin and testosterone for over 5 weeks. The complete recovery of these functions was observed 10 weeks after the injection. The repeated injection of the microspheres at intervals of 2 or 4 weeks achieved persistent suppression of steroidogenesis after an initial transient flare-up and beneficially avoided the "acute-on-chronic response." This depot formulation is expected to assure patient compliance and produce stronger therapeutic effects than the daily solution. PMID- 1907737 TI - TRH-induced tachyphylaxis: present in the smooth muscle but not in the cardiorespiratory effects. AB - The development of tachyphylaxis to the pressor, tachycardiac, ventilatory and smooth muscle effects of thyrotropin-releasing hormone (TRH) was studied. Subsequent administrations of increasing doses of TRH (0.1-1000 nmol/kg intracerebroventricularly), at 20 min. intervals in urethane-anesthetized rats dose-dependently increased the mean arterial blood pressure, heart rate and minute ventilation volume. At all doses the effect on mean arterial blood pressure was apparent at least 20 min. after each injection whereas at low doses (0.1-1 nmol/kg) the duration of the effects on heart rate or minute ventilation volume were shorter. The cardiorespiratory effects of TRH 10 nmol/kg intracerebroventricularly did not subside completely within an observation period of 1 hr. However, a repeated administration of TRH at 1 hr resulted in the levels of mean arterial blood pressure, heart rate and minute ventilation volume not statistically different from the peak levels of the first injection. While the cardiorespiratory effects of TRH were long-lasting, the TRH induced inhibition of the contractions of the rat duodenal smooth muscle lasted only 12-18 sec. The TRH treated duodenal preparation responded normally to noradrenaline but remained unresponsive to further administrations of TRH until washed extensively. When the medium after cessation of the TRH response was transferred into another chamber with an untreated preparation, a full response was resulted. Inhibitors of TRH metabolism, bacitracin, EDTA and iodoacetamide, did not prolong nor enhance the response. Likewise, a stable TRH-analogue MK-771 did not produce any longer response than TRH. It is concluded that no tachyphylaxis was produced to the neurally mediated pressor, tachycardiac or ventilatory effects of TRH.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1907738 TI - Behavioural and biochemical effects of subchronic treatment with raclopride in the rat: tolerance and brain monoamine receptor sensitivity. AB - Male Sprague-Dawley rats were treated with the dopamine (DA) D2 receptor blocking agent raclopride 0.5 or 8.0 mg kg-1 subcutaneously (1.0 and 16.0 mumol kg-1, respectively), twice daily for 21 days. The animals treated with raclopride gained weight at the same rate as saline controls, and gross observation did not indicate any behavioural abnormalities due to the subchronic raclopride treatment. Possible changes in brain DA receptor sensitivity due to prolonged blockade of DA receptors were evaluated in behavioural and biochemical models. There were no effects on locomotor activity, as observed by means of photobeam equipped activity cages, 24 hr or 72 hr after withdrawal of 0.5 or 8.0 mg kg-1 subchronic raclopride treatment. Twenty-four hr after withdrawal of the raclopride treatment there was an increased post-synaptic DA receptor sensitivity as evidenced by increased behavioural and biochemical responses to apomorphine, and by an attenuated response to acute raclopride treatment, 0.1 mg kg-1. Thus, there was an increase in locomotor activity by the apomorphine treatment in animals pretreated with the 8 mg kg-1 dose, as compared to the response obtained in saline controls. Furthermore, the suppression of locomotor activity in saline controls produced by acute raclopride treatment was dose-dependently antagonized by the raclopride pretreatment and this also applied to the increase in striatal DOPAC levels produced by acute raclopride treatment. Finally, there was an increased DA receptor sensitivity presynaptically as evidenced by an enhanced effect on striatal DOPA levels by apomorphine in rats treated with NSD 1015 and reserpine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1907739 TI - [Sleep-related respiratory disorders: from syndromes to risk factors]. AB - In the past, sleep related breathing disorders (SRBD) have been described rather heterogeneously in terms of complex diseases, syndromes. During the past ten years, the relevant pathogenetic mechanisms of most of the SRBD could be defined, and data concerning their epidemiology were collected. Epidemiology and dangerousness being relevant criteria, the obstructive sleep apnea syndrome must be regarded as the most considerable SRBD. According to ICSD, the prevalence of a manifest obstructive sleep apnea syndrome is estimated at 1% of the entire population at least. Our measurings have shown that more than 10% of the middle aged (20 to 60 years) male population suffer from 10 and more mixed obstructive apneas per hour of sleep. In this group, also the other pathogenetic factors for the obstructive sleep apnea syndrome, namely hyperventilation and fragmentation of sleep due to central arousal reactions, are found. All these patients snore, and there is a broad transition from primary snoring, which has no effects on the cardiovascular system and the blood gases, via obstructive snoring up to inter apneic snoring. With the help of today's technical equipment, it is possible to determine the role of subclinical SRBDs in terms of risk factors, e.g. for cardiovascular diseases. We expect a plain contribution to the clearing up of instances of arterial hypertonus, early invalidity, and mortality. PMID- 1907740 TI - [Studies on the influence of releasing hormones TRH and CRH on respiratory regulation]. AB - Patterns of neuroanatomical distribution of Thyrotropin-releasing hormone (TRH) and Corticotropin-releasing hormone (CRH) and of their receptors in brain areas of humans and of animals suppose a regulating function of both peptides on regulation of respiration. In experimental animals TRH induces rhythmical and synchronous firing of defined neurons of nucleus tractus solitarii. In fetal sheep, endogenous and exogenous CRH promotes maturation of breathing rhythm genesis. In own human studies we demonstrated a modulation of respiration in healthy test-subjects - predominantly a stimulation of respiration - by systemic TRH and CRH. This effect persists also during hypercapnia, as we showed in patients and in 12 healthy test subjects while re-breathing CO2: when compared to placebo, CRH i.v. (200 micrograms. Bissendorf, Hannover, FRG) induces a significant (p less than 0.0001) shift of the ventilatory response curve to the left (petCO2 vs minute volume). Stimulation of respiration by CRH is independent of activation of the pituitary-adrenal axis. At present two analogues of CRH are available for application in humans (as a diagnostic of endocrinological disorders): human CRH and ovine CRH. Both analogues are comparably effective in stimulation of ventilation although sequence of effects is different in both analogues. We also evaluated the effect of CRH in 10 aged patients who were under prolonged respirator therapy after major abdominal surgery; both human and ovine CRH (100-200 micrograms i.v.) induced a profound and long lasting stimulation of ventilation under assisted respirator therapy. Vigilance was also markedly increased in all patients and thus was of therapeutic value. CRH also has a potential to alter sleep architecture in healthy and in diseased persons.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1907741 TI - [Follow-up study of patients with sleep-related respiration disorders without obstruction of the upper airways (central apnea)]. AB - This is a report on 16 patients with central asphyxia. All patients had respiratory global insufficiency. The period of observation was 3.5 years. In all cases deterioration of the blood gases took place. All patients died due to right heart failure. Implantation of a diaphragm pacer caused an increase of pO2 during sleep. PMID- 1907742 TI - Induction of experimental murine granuloma formation against Schistosoma japonicum eggs produced by in vitro ova deposition, in vitro tissue extraction, or lyophilization. AB - Fresh eggs, laid by Schistosoma japonicum adult worms in vitro or recovered from tissue after trypsin digestion, as well as non-viable lyophilized eggs were injected into mice via the cecal vein. The freshly laid eggs induced a marked, maximal reaction at 2 weeks after implantation. This reaction was indistinguishable from that seen early in naturally infected mice. Lyophilized eggs induced granulomas only one-tenth the size of those formed around freshly laid eggs. Maximal granulomatous reactivity was not seen until the 4th week after implantation and the intensity of cellular reactivity and associated histopathological change was much lower than that observed with freshly laid eggs. Reactions against live, tissue-extracted eggs were quantitatively and temporally intermediate between those observed against laid and those surrounding lyophilized eggs. The results suggests that these differences in granuloma formation are due to variable quantities of locally produced cytotoxic materials and/or antigen that stimulate immune reactions of different intensities. PMID- 1907743 TI - Decrease of liver glycogen content in golden hamsters infected with plerocercoids of Spirometra erinacei. AB - Liver glycogen content decreased in golden hamsters experimentally infected with plerocercoids of Spirometra erinacei. The activity of glycogen synthase a decreased significantly in infected animals, whereas that of glycogen phosphorylase a was not significantly affected. These observations suggest that changes in glycogen content were not attributable to increased glycogenolysis, but rather resulted from suppressed glycogenesis. Plasma immunoreactive insulin (IRI) concentrations in infected animals were slightly lower than those in controls, but the differences were not statistically significant. Plasma glucagon concentrations were significantly higher in infected animals. These results suggest that the suppression of glycogen synthase activity in S. erinacei infected hamsters was attributable to enhanced levels of glucagon and that enhanced secretion of glucagon was caused by parasite-induced hypoglycemia. PMID- 1907744 TI - Role of the forebrain in oculomotor function. PMID- 1907745 TI - The prefrontal cortex and its relation to behavior. AB - The prefrontal cortex is critical for temporal organization of behavior. It mediates cross-temporal sensory-motor contingencies, integrating motor action (including speech) with recent sensory information. It performs this role through cooperation of two cognitive functions represented in its dorsolateral areas: short-term memory (STM) and preparatory set. Supporting data have been obtained from monkeys performing delay tasks, which epitomize the principle of cross temporal contingency. In a given trial, the animal performs an act contingent on a sensory cue given a few seconds or minutes earlier. During the delay between cue and response, cells in dorsolateral prefrontal cortex show sustained activation. Two cell categories can be identified in tasks in which cue and response are spatially separate. Cells of the first participate in STM: Their activation tends to diminish as the delay progresses; in some, the activation level depends on the particular cue received. Similar cells are found elsewhere in cortex. Cells of the second category seem to take part in preparation of motor response: Their activation tends to increase in anticipation of it and may be attuned to the particular movement the cue calls for. This cell type is rare outside of frontal cortex. The temporally integrative function of the prefrontal cortex is probably based on local interactions between "memory" and "motor-set" cells, as well as on neural associations between prefrontal cortex and posterior cortical areas. PMID- 1907746 TI - [Sex-determination in Drosophila melanogaster: mechanism of sex-specific splicing]. PMID- 1907747 TI - [A ras guanine nucleotide exchange factor and ras-mediated signal transduction]. PMID- 1907748 TI - Analytic representation of the backscatter correction factor at the exit of high energy photon beams. AB - In high energy X-ray beams, the dose calculated near the exit surface under electronic equilibrium conditions is generally overestimated since it is derived from measurements performed in water with large thickness of backscattering material. The resulting error depends on a number of parameters such as beam energy, field dimensions, thickness of overlying and underlying material. We have systematically measured for four different energies and for different combinations of the above parameters, the reduction of dose due to the lack of backscatter. This correction is expressed as a multiplicative factor, called "Backscatter Correction Factor" (BCF). This BCF is larger for lower energies, larger field sizes and larger depths. The BCF has been represented by an analytical expression which involves an exponential function of the backscattering thickness and linear relationships with depth, field size and beam quality index. Using this expression, the BCF can be calculated within 0.5% for any conditions in the energy range investigated. PMID- 1907749 TI - Stimulation of rat adrenal medulla can induce differential changes in the peptide and mRNA levels of chromogranins, neuropeptides and other constituents of chromaffin granules. AB - The levels of various components of chromaffin granules were determined in rat adrenals after treatment with several stimulants. After reserpine the levels of calcitonin gene-related peptide (CGRP), neuropeptide Y (NPY) and chromogranin B but not those of chromogranin A and secretogranin II were elevated. On the other hand, the mRNA of chromogranins A, B and secretogranin II were significantly increased. Treatment with oxotremorine or nicotine (multiple injections for 2 or 3 days) induced analogous changes for peptide and mRNA levels, however, the increases were smaller and for the mRNA less consistent. A single injection of oxotremorine or nicotine raised only the levels of CGRP and NPY and of the NPY mRNA whereas those of the chromogranins and their respective mRNAs remained unaltered. Amongst the membrane proteins only the levels of dopamine beta hydroxylase are increased after prolonged stimulation, whereas those of cytochrome b-561, carboxypeptidase H and synaptin/synaptophysin (SYN) remain unaltered. Thus, the biosynthesis of chromaffin granules can be regulated in quite sophisticated patterns. PMID- 1907750 TI - Is TNF alpha involved in early susceptibility of Trypanosoma cruzi-infected C3H/He mice? AB - Early wasting and subsequent mortality may occur in mice of some inbred strains following infection with Trypanosoma cruzi. It was hypothesized that TNF alpha/cachectin might be involved in this process. Thus, sera collected from mice of strains differing in their susceptibility or resistance to Trypanosoma cruzi infection were checked for the presence and level of TNF alpha, a cytokine able to exert acute toxic effects. C3H/HeJ or C3H/HePas (susceptible), BALB/c (intermediate) and C57BL/6 (resistant) mice were infected with the CL or Colombian strain of Trypanosoma cruzi, and TNF activity was measured in the sera during the acute phase of the infection. Only serum collected from infected C3H/He mice contained TNF activity. However, TNF activity could be measured in serum of all strains, following LPS infection, indicating that the infection was able to prime macrophages of infected mice to secrete TNF alpha. The TNF alpha/cachectin release in the sera of C3H mice may play a role in the early wasting and death of these mice after Trypanosoma cruzi infection. PMID- 1907751 TI - Chagas' disease: Trypanosoma cruzi vs. the host immune system. 36th forum in immunology. PMID- 1907752 TI - Chagas' disease: Trypanosoma cruzi vs. the host immune system. PMID- 1907753 TI - Pathogenesis of Chagas' disease. PMID- 1907754 TI - Macrophage activation and resistance to Trypanosoma cruzi infection. PMID- 1907755 TI - Natural anti-Gal antibodies prevent, rather than cause, autoimmunity in human Chagas' disease. PMID- 1907756 TI - Immunological aspects of the morbidity of human Chagas' disease. PMID- 1907757 TI - [Hereditary lysosomal diseases in Mexico. III. Laboratory diagnosis of sphingolipidosis]. AB - Enzymatic determinations of the levels of lysosomal enzymes in serum or leukocytes samples have been carried out for the diagnosis of 7 sphingolipidosis. This methodology has allowed us to study 49 homozygotes and 33 close relatives at risk for the carrier state of a particular sphingolipidosis. So far we have diagnosed: 21 Gaucher's disease patients, 17 metachromatic leukodistrophy, 4 Niemann-Pick, 4 GM2 gangliosidosis, 2 Fabry and one GM1 gangliosidosis. Limitations in the performance and interpretation of the levels of the defective enzyme in heterozygotes, homozygotes and those variants not detected with the assays described are discussed. PMID- 1907758 TI - [Efficacy and costs of treatment with ceftriaxone compared to ampicillin gentamycin in acute pyelonephritis]. PMID- 1907759 TI - Bacteremia and septic arthritis caused by Moraxella catarrhalis. AB - Moraxella catarrhalis was isolated from blood from a 41-year-old man who had a 24 hour history of increasing pain in and swelling of the left knee. No history of trauma, arthropathy, fever, chills, cough, or chest pain was noted. What is believed to be the first case of bacteremia caused by M. catarrhalis that was associated with septic arthritis is described in this report. The case presented suggests the pathophysiology of this rare condition. One previous case of septic arthritis caused by M. catarrhalis without documented bacteremia has been reported. PMID- 1907760 TI - The use of recombinant factor VIII in the management of hemophilia. AB - Recombinant factor VIII is currently in the late stages of clinical trials. The available studies indicate that the product is safe and well-tolerated, and appears to be free of virus diseases such as HIV and hepatitis infections. Based on these early studies, recombinant coagulation factors appear to have enormous promise and potential for transfusion medicine. The synthesis of large quantities of safe material may lead to the development of techniques for daily administration of factor VIII aimed at the prevention of joint and soft tissue bleedings. There is also the promise of decreased costs, as techniques for the efficient synthesis of recombinant proteins are refined further. PMID- 1907761 TI - Role of prostaglandin E2 on defective interferon-gamma production during type B acute viral hepatitis. AB - Interferon-gamma (IFN-gamma) and prostaglandin E2 (PGE2) production was evaluated in cultured peripheral blood mononuclear cells taken from patients with type B acute viral hepatitis at the onset of symptoms, at 1st and 2nd week of disease, and from healthy controls. Concanavalin A-stimulated cells cultured for 24, 48 and 72h showed significantly higher IFN-gamma levels compared to basal release in both groups, whereas no statistically significant differences were found in most experimental conditions as regard PGE2 synthesis. No differences were found in IFN-gamma production by comparing patients with acute viral hepatitis to the control group, whereas PGE2 was significantly increased during the disease. IFN gamma and PGE2 levels did not show any significant change in acute viral hepatitis during the follow-up. A statistically significant correlation was found only in control group between IFN-gamma and PGE2 levels in unstimulated cultures. PGE2 seems to play a central role in regulating interferon production during viral infection. This may suggest a new therapeutic approach in viral hepatitis utilizing a combination of interferon and prostanoid inhibitory substances, above all in patients who do not respond to interferon therapy alone. PMID- 1907762 TI - Increase of plasma tissue-plasminogen activator antigen levels after induced abortion. AB - We previously reported that plasma thrombotic activity is transiently increased immediately after induced abortion. However, changes in the fibrinolytic system have not yet been studied. Plasma tissue-plasminogen activator (t-PA) antigen levels were studied before and after abortion induced during the first trimester of pregnancy. Compared with the preoperative level (1.68 +/- 0.15 ng/ml), t-PA level was significantly increased (2.78 +/- 0.55 ng/ml, p less than 0.01) 15 min after the induced abortion, while it almost returned to the preoperative values (2.09 +/- 0.40 ng/ml) 2h later. This finding suggests that fibrinolytic activity is transiently increased immediately after the induced abortion, acting as a defense mechanism against thrombosis. PMID- 1907763 TI - Protein kinase C regulates MHC-class II expression on endothelial cells. AB - Cultured endothelial cells (EC) were negative for class II antigen in native state, whereas 49% of the endothelial cells began to express this antigen after 24 h of interferon-gamma (IFN-gamma) stimulation. IFN-gamma induced relatively slowly the elevation of class II antigen on endothelial cells, since it took more than 10 h before the first signs of mRNA signal of class II were detected. Class II antigen instead began to appear during 16-20 h after the initiation of IFN gamma treatment. Committed step analysis revealed that IFN-gamma could not be washed away at any time point without affecting the number of class II positive cells after a 24-h incubation period. Protein kinase C (PKC) activator phorbol-12 myristate-13-acetate (PMA) could partially mimic IFN-gamma effect in inducing class II expression on endothelial cells. PMA together with another PKC activator arachidonic acid (AA) induced class II expression on endothelial cells as well as IFN-gamma. The crucial role of activation of PKC in the IFN-gamma induced class II expression can also be demonstrated by using PKC inhibitors in combination with IFN-gamma. PKC inhibitor H7 was able to decrease almost totally IFN-gamma induced class II induction both on the mRNA as well as on the protein level. PKC activation has often been linked to its translocation from the cytosolic compartment to the inner surface of the plasma membrane. IFN-gamma induced a transient 2.4-fold increase in the membrane-associated PKC in endothelial cells within 10 min after the initiation of the stimulus. Taken together these data show that IFN-gamma requires a long time before class II induction. The regulation of class II expression occurs at transcriptional level and requires de novo protein synthesis as shown by cycloheximide inhibition. PMID- 1907764 TI - In situ hybridization of interferon-gamma producing peripheral blood mononuclear cells. AB - Individual interferon-gamma (IFN-gamma) producing cells in activated human peripheral blood mononuclear cells (PBMC) were characterized by in situ hybridization using [35S]-labelled antisense RNA probes. The proportion of positive cells expressing IFN-gamma mRNA varied according to the substances used for stimulation. IFN-gamma mRNA expressed a relatively low percentage of 1-8% PBMC after a single stimulus with mitogens or OKT-3 antibody and 20-30% of the cells were identified to synthesize IFN-gamma mRNA after stimulation with PHA + P MA + OKT-3 antibody. The expression of IFN-gamma mRNA and production of the lymphokine was dependent on accessory cells. If accessory cells were replaced by recombinant interleukin-1 (IL-1) plus interleukin-6 (IL-6), then T-cell proliferation to phytohaemagglutinin (PHA) could be partially restored and measurable amounts of IFN-gamma were detected. The addition of interleukin-2 (IL 2) or phorbol-12-myristate-13-acetate to T cells stimulated with PHA, IL-1 and IL 6 did not restore the production of IFN-gamma to an extent comparable to that produced by T cells stimulated in the presence of accessory cells. In further studies, depletion of T-cell subsets showed that CD3+, CD4+, CD8+, CD29+ and CD45RA+ cells were involved in IFN-gamma production after mitogenic stimulation. In conclusion, our data demonstrate that IFN-gamma production is dependent on signals from accessory cells and IFN-gamma is synthesized by only a small proportion of T cells, that did not belong to a unique population, characterized by conventional cellular surface antigens. PMID- 1907765 TI - Reduced CD4 and CD8 expression in human thymuses treated with soluble CD4. AB - Recent data suggest that accessory molecules like CD4 and CD8 act as co-receptors in intrathymic T-cell development. Soluble CD4 (sCD4) molecules offer a novel experimental approach to investigate the relevance of CD4 interaction with its putative intrathymic receptor for T-cell maturation. We attempted to inhibit binding of surface CD4 on thymocytes to its intrathymic receptor competitively by introduction of human sCD4 into human thymus tissue cultures. Our results demonstrate that sCD4, while not affecting peripheral T-cell responses as shown in control experiments, significantly affects intrathymic development of T lymphocytes. Immature CD4CD8 double positive (DP) thymocytes responded with reduced expression of both CD4 and CD8 molecules. This phenomenon could be followed up to the stage of single positive (SP) thymocytes: density of CD4 molecules on CD4 SP thymocytes and, even more interestingly, CD8 expression on CD8 SP cells, were reduced, indicating that the effect observed in immature DP thymocytes persists during their further development. Beyond that, analysis of T cell receptor (TCR) expression in the low density CD4CD8 DP population revealed a slight decrease of alpha beta-TCR surface expression, suggesting a possible role of CD4 engagement in the generation of TCR in man. Since sCD4 is considered a therapeutical agent in HIV infections, these findings are not only of basic but also of clinical interest. PMID- 1907766 TI - Tumour necrosis factor-alpha induces neutrophil-mediated injury of cultured human endothelial cells. AB - We investigated the ability of TNF-alpha to mediate damage of endothelial cells in the presence of neutrophils, by measuring detachment of cultured human umbilical vein endothelial cells (HUVEC). Endothelial cell detachment was increased from 5% to about 75% by the presence of 1-10 ng/ml TNF-alpha during incubation with neutrophils, whereas negligible endothelial cell lysis was observed as measured by 51Cr release. TNF-alpha was compared with the cytokines IL-1 alpha and IFN-gamma and with PMA and LPS. Both TNF-alpha and PMA appeared to be strong triggers for neutrophil-induced endothelial cell detachment, whilst reduced injury was seen after addition of IL-1 alpha and LPS. IFN-gamma did not induce endothelial cell detachment, but potentiated the effect of both TNF-alpha and IL-1 alpha. TNF-alpha-induced endothelial cell detachment was neutrophil dependent, since pre-incubation of neutrophils, but not pre-incubation of endothelial cells with TNF-alpha, caused endothelial cell detachment. Thus, TNF alpha-induced increase in neutrophil-adhesiveness of HUVEC was found not to be essential for endothelial damage. Pre-incubation of neutrophils in suspension with TNF-alpha induced rapid activation, followed by nearly complete deactivation of neutrophils, as measured by their capacity to induce detachment of endothelial cells after removal of TNF-alpha. These results indicate that local presence of TNF-alpha might be critical in tissue or organ damage during early, neutrophil mediated inflammatory processes, independent of enhanced adhesiveness of endothelium for neutrophils. PMID- 1907767 TI - Impaired balance of interleukin-4 and interferon-gamma production in infections with Schistosoma mansoni and intestinal nematodes. AB - In chronic infection with Schistosoma mansoni, IL-4 and IFN-gamma are co modulated in opposite directions. This was shown when testing sera and cell culture supernatants from 31 Brazilian patients with schistosomiasis before, and three months after treatment with praziquantel. Thorough examinations were undertaken to account for polyparasitism with intestinal nematode infections involving tissue migrating larval stages that may induce analogous changes. Controls free of S. mansoni included a group (n = 17) matching the schistosomiasis patients' parasitation by intestinal nematodes and a group (n = 16) free of helminths other than T. trichiura. Serum IL-4 was greater than 20 pg/ml in 81% of schistosomiasis patients but in only 35 and 25%, respectively, of controls with and without intestinal nematodes. IL-4 data correlated inversely with the mitogen-induced IFN-gamma synthesis. Generation of IL-4 in response to phorbol esters was related to the intensity of infection by schistosomes and intestinal nematodes. The parasitological status three months after therapy with either praziquantel or mebendazole revealed a dichotomy: whereas the ratio of IFN gamma to IL-4 generated in vitro was identical in uninfected controls and in patients who cleared the parasites, failure to eliminate the parasites was associated with lower IFN-gamma/IL-4 ratios generated in vitro. PMID- 1907768 TI - [Post-transfusional hepatitis. Preliminary study]. AB - In Venezuela post-transfusional hepatitis (PTH) data is unknown. We studied, prospectively, 147 patients who received blood transfusions (1 to 48 different blood components). They were screened for HBsAg (Ortho HBsAg Elisa Test System), anti HBc (Ortho HBc Elisa Test System and CORZYME, Abbott Laboratories) and amino transferases (Doles), before and after transfusions. Only the last 36 patients were tested for anti HCV (Ortho HCV antibody Elisa Test)R from the beginning. The test were performed at 2, 7, 12 and 24 weeks subsequently in the negative recipients. PTH for type B virus was 3.8% (5/131), and for NANBH 2.7% (3/110). In both groups those recipients who had more transfusions had the greatest incidence of PTH. We conclude that anti HBc and ALT must be done in all blood donors to prevent the occurrence of PTH either B virus or NANBH. We suggest also, to include anti HCV screening in blood donors as a mean to make blood transfusion safer. PMID- 1907769 TI - A prospective trial comparing Biobrane, Duoderm and xeroform for skin graft donor sites. AB - Many new dressings have been introduced for use on split-thickness skin graft donor sites in an effort to reduce pain at the donor site and decrease healing time, while maintaining a low infection rate and cost. To assess these factors in two such dressings, Biobrane (temporary wound dressing) (Winthrop) and Duoderm (hydrocolloid dressing) (Convatec), we compared them with a conventional fine mesh gauze dressing, xeroform, in a prospective, randomized study of 30 donor sites in the same number of patients. Wounds were considered healed when they were 100 per cent re-epithelialized and required no further dressings. Patient self-assessment of pain was quantified on a scale of zero to ten, with ten being the most severe pain. Donor sites dressed with xeroform had a healing time of 10.5 days, which was significantly better (p less than 0.05) than Duoderm (15.3 days) or Biobrane (19.0 days), although the protocol for Duoderm use (wound visualization at seven day intervals) extended the apparent healing times in this group. Duoderm was the most comfortable dressing (0.53 grade) when compared with Biobrane (1.44) and xeroform (2.41, p less than 0.05). No infections occurred in donor sites dressed with xeroform, but two developed in patients using Biobrane. One patient with a Duoderm dressing had a donor site infection during a drug related neutropenic reaction. Xeroform was the least expensive dressing to use ($1.16 per patient), followed by Duoderm ($54.88 per patient) and Biobrane ($102.57 per patient). The results of our study confirm the usefulness of xeroform as a donor site dressing as it promotes relatively rapid healing, is easy to use and is inexpensive. We found Duoderm to be ideal for smaller donor sites when pain could be significantly reduced with minimal increase in cost. Biobrane is too costly and the infection rate too high for it to be used routinely as a skin graft donor site dressing. PMID- 1907770 TI - Disturbance of basal and stimulated serum levels of intact parathyroid hormone in primary hyperparathyroidism. AB - In patients with primary hyperparathyroidism, measurements were made of basal and stimulated levels of intact parathyroid hormone (PTH). The basal PTH values were elevated in all but six of 89 patients and provided clear separation towards normal individuals (n = 75) and patients with hypercalcemia of other origin (n = 34). The PTH value correlated with the serum calcium concentration in hyperparathyroidism and with the weight of excised parathyroid adenomas but not with that of chief cell hyperplasias. A constant ethylenediaminetetraacetic acid infusion during 60 minutes of induced essentially linear reductions of plasma ionized calcium concentrations, averaging 0.02 mmol/L/10 minutes, which were associated with swift, curvilinear, elevations of PTH levels that reached a plateau after 10 to 20 minutes. The increment in serum PTH level correlated with the basal PTH value both in patients with hyperparathyroidism and controls. However, in proportion to the much greater glandular mass in the patients with hyperparathyroidism, the secretion of PTH was relatively reduced. The findings support the value of the intact PTH assay in the differential diagnosis of hypercalcemia and show that PTH secretion in vivo is extremely sensitive to hypocalcemic stimulation, that the pathological parathyroid tissue in hyperparathyroidism is characterized by a reduction of hormone release per unit weight, and that the hormone secretion in hyperparathyroidism operates closer to its maximal capacity than under normal circumstances. PMID- 1907771 TI - Molecular forms of plasminogen activator inhibitor-1 (PAI-1) and tissue-type plasminogen activator (t-PA) in human plasma. AB - Molecular forms of plasminogen activator inhibitor-1 (PAI-1) and tissue-type plasminogen activator (t-PA), identified by gel filtration and specific immunoassays, were studied in plasma from subjects with normal and elevated PAI-1 levels before and after in vitro or in vivo addition of t-PA. In normal plasma, PAI-1 occurs in three molecular forms, a Mr greater than 700 KDa inactive form of heterogeneous composition, an active 450 KDa form containing PAI-1/vitronectin complex and an inactive peak at Mr 50 KDa containing free PAI-1. Stimulation of platelets results in a significant increase of the 50 KDA form and a slight increase of the 450 KDa form. Patients with increased PAI activity levels have an increase of both the 450 KDa and the 50 KDa forms, whereas patients with thrombotic thrombocytopenic purpura have an increased 50 KDa form. In normal plasma, collected in the presence or absence of D-Phe-Pro-Arg-CH2Cl, t-PA occurs primarily as a Mr greater than 700 KDa form containing t-PA/PAI-1 complex. Addition of high concentrations of t-PA (70 ng/ml) to plasma in vitro or t-PA injection in vivo, results in t-PA inhibitor complexes, including t-PA/ alpha 2 antiplasmin. It is concluded that in subjects with increased PAI-1 levels in plasma, PAI-1 may occur as high molecular weight complexes with vitronectin of which 450 KDa was the most important part and as a 50 KDa inactive form; t-PA circulates primarily in complex with inhibitors. Thus, some of the molecular interactions between PAI-1, t-PA and vitronectin, previously demonstrated in purified systems in vitro, also occur in plasma. PMID- 1907772 TI - Disruption of the blood-brain barrier in open and closed cranial window preparations in rats. AB - The goal of this study was to determine whether the severity of disruption of the blood-brain barrier during acute hypertension is similar in open and closed cranial window preparations. Intravital fluorescent microscopy and fluorescein labeled albumin were used to evaluate disruption of the blood-brain barrier under control conditions and during acute arterial hypertension in 10 rats equipped with an open cranial window and in six rats equipped with a closed cranial window. Permeability of the blood-brain barrier was quantified by calculating the clearance of fluorescein-labeled albumin and by counting the number of microvascular leaky sites under control conditions and during acute hypertension. Pressure in cerebral venules and intracranial pressure were measured in rats equipped with an open cranial window and a closed cranial window, respectively, under control conditions and during acute hypertension. In rats equipped with an open cranial window, arterial pressure increased from 118 +/- 6 to 189 +/- 3 mm Hg (mean +/- SEM) and pial venous pressure increased from 7 +/- 1 to 22 +/- 3 mm Hg during acute hypertension induced with 30 micrograms/kg/min phenylephrine for 5 minutes. In addition, the clearance of fluorescent albumin increased from 0.11 +/- 0.03 to 1.2 +/- 0.4 ml/sec x 10(-6) and the number of microvascular leaky sites increased from 0 to 25 +/- 1 during phenylephrine infusion. In rats equipped with a closed cranial window, arterial pressure increased from 122 +/- 5 to 187 +/- 7 mm Hg and intracranial pressure increased from 3 +/- 1 to 12 +/- 1 mm Hg during the intravenous infusion of 30 micrograms/kg/min phenylephrine for 5 minutes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1907773 TI - [Developments in the care (of the aged) and rights of family and volunteers]. PMID- 1907775 TI - Sarcoptic mite hypersensitivity and skin lesions in slaughtered pigs. AB - The association between papular skin lesions in slaughtered pigs and hypersensitivity to Sarcoptes scabiei var suis was examined in experimental and field studies, and by the retrospective analysis of monitoring records obtained at slaughter. A causal role for S scabiei was indicated by the production of lesions in experimentally infested pigs, by increased clinical mange in herds having high lesion scores, and by a reduction in the severity of lesions after the implementation of more intensive mange control measures. The specificity of the lesions as an indicator of sarcoptic mite hypersensitivity was estimated to be 0.92 from experimental data and 0.79 from field data. Generalised lesions were rare in mange free pigs, indicating that such lesions were highly specific (1.0 from experimental data, greater than 0.98 from field data) for mange. The assessment of the severity of the lesions in samples of slaughtered pigs appears to be a useful aid to assessing the severity of sarcoptic mange in pig herds. PMID- 1907774 TI - [The adaptive response to mitomycin C exposure in the hyper-radioresistant mutant Escherichia coli Gamr444]. AB - Adaptive response to mitomycin C (MC) (lethal effect and recovery of molecular mass of DNA) in hyper-radioresistant mutant Escherichia coli Gamr444 have been investigated. This mutant is more resistant to MC than parent strain E. coli K12 AB1157. Adaptation of Gamr444 mutant to MC in nonlethal concentrations increases its resistance to MC in lethal concentrations with dose modification factor (DMF) 2.4 at the LD90 level. During the adaptation of this mutant to methyl-methane sulfonate (MMS) its resistance to this agent increases with DMF by 2.2 and resistance to MC with DMF by 1.5 times. During the adaptation of Gamr444 mutant to MC its resistance to MMS increases with DMF by 1.5 times. Adaptive response to MC abolishes by chloroamphenicol treatment during the adaptation. Adaptive response to nitrogen mustard (HN2) in E. coli Gamr444 is absent (HN2 induces cross-links in DNA as MC). Degradation of DNA following the formation of cross links in DNA takes place. Adaptation to MC in Gamr444 mutant leads to restoration of DNA molecular mass which is more quicker than in the case without adaptation. Adaptive restoration of DNA molecular mass after the MC treatment is absent in E. coli K12 AB1157. The repair of cross-links in DNA after the treatment of HN2 in Gamr444 mutant takes place with equal rate both in the case of adaptation to HN2 and in the case without adaptation. It is proposed, that under the treatment of MC in E. coli Gamr444 the ada-alkA-dependent adaptive response takes place. This adaptive response is connected with alkylation of O6-guanine and elimination of the product by O6-alkyl-DNA-alkyltransferase. Partial recA-dependency of the adaptive response to MC allows to suggest the participation of another inducible system. The nature of this system is unknown. PMID- 1907776 TI - Rapid presumptive identification of type B P multocida from haemorrhagic septicaemia. PMID- 1907778 TI - Health access report. The evolution of nursing reimbursement in the USA. PMID- 1907777 TI - Suppression of cell-mediated immunity by purified aflatoxin B1 in broiler chicks. AB - The effect of purified aflatoxin B1 on cell-mediated immunity (CMI) in broiler chicks was assessed using doses of 0.3 and 1 mg/kg feed from hatching to 6 weeks of age. Total lymphocyte and T lymphocyte counts and the 2,4-dinitrofluorobenzene skin sensitivity test, graft-versus-host reaction and nitroblue tetrazolium salt reduction tests were used to evaluate CMI. Both doses of aflatoxin B1, including the apparently nontoxic dose of 0.3 mg/kg feed, caused a significant (P less than 0.05) decline in CMI. The functional activity of splenic macrophages was decreased significantly (P less than 0.05) by both doses of the toxin. PMID- 1907779 TI - [Gas chromatograms of fatty acids from Rickettsia and their similarities]. AB - Fatty acid compositions of 7 strains of Rickettsia were analyzed by a on-line GC/MS system. These strains were R. prowazekii E, R. conorii Simko, R. rickettsii R, R. sibirica Barbash and 246, R. sinkiangensis Jinghe, and R. heilungkiangensis 54. The samples were purified by means of the concentrated salt-ether method. There were about 50 peaks in the fatty acid profiles, and 16 of these peaks were determined, i.e. C22:0, C19:0, C18:0, C18:1, C18:2, C17:0, C16:0, C16:1, 3-OH C14:0, C15:0, C14:0, C13:0, 2-OH-C12:0, C12:0, 2-OH-C10:0, and C11:0. The major fatty acids were the saturated straight chain acids (e.g. C16:0, C18:0, C14:0) and the unsaturated straight chain acids (e.g. C18:1, C18:2, C16:1). Similarities of fatty acid profiles of tested strains were discriminated by the improved Kulik Vincent method. The result showed that the KV's coefficient of strains Jinghe and 246 was 97.0%, and the KV's coefficient of strains 54 and the others was 81.6 94.6%. PMID- 1907780 TI - [Length of stay, diagnostic classification, treatment outcome and discharge status of patients living alone or not of German federal hospitals]. AB - To assume that the length of stay in hospital depends on whether a patient lives alone or not belongs to conventional wisdom in social epidemiology. In the DTI (diagnosis- and therapy) index of Infratest Health Research a randomly selected number of patients of German acute hospitals was asked whether they were living alone or not. Measuring the average length of stay in hospital and the average success of treatment with these data, only a marginal effect of the variable "social situation" remains after correcting for age. The social situation is a very influential variable, however, when considering where patients are released to. A much greater margin of male and female geriatric patients of acute hospitals leave the hospital to go into institutions of long term care and into other hospitals. The social situation proves to be less important within the acute hospital, but to have a severe influence in the process of leaving it. PMID- 1907781 TI - Variations in total bile acid concentration in serum of dogs after a test meal. AB - The purpose of this study was to examine the variations in total serum bile acid (SBA) concentration following oral administration of corn oil (3.0 ml per kg body weight) to six fasted healthy dogs using a previously validated automated method (JENSEN, 1991) for the determination of SBA concentration. The preprandial SBA concentration was 2.22 mumol/l (0.64-6.41 mumol/l) (median, 0.025-0.975 fractiles). In the 2-6 hours postprandial period, all the SBA concentrations were significantly different from the preprandial value, but not significantly different from each other. For the total 2-6 hours postprandial period the SBA concentration was 7.89 mumol/l (1.39-22.24 mumol/l). From these results it may be suggested that the reference range for the preprandial SBA concentration in dogs is 0.64-6.41 mumol/l, and that the reference range for the postprandial SBA concentration in a blood sample obtained 2 hours after oral administration of corn oil is 1.39-22.24 mumol/l. PMID- 1907782 TI - Evaluation of fasting and postprandial total serum bile acid concentration in dogs with hepatobiliary disorders. AB - The fasting and 2 h postprandial total serum bile acid concentrations (FSBA and PSBA), alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, bilirubin (Total), and retention of bromosulphthalein were determined in a group of dogs with various hepatobiliary disorders as well as in a group of dogs with other diseases than hepatobiliary disorders. Although FSBA and PSBA were generally elevated in cases of hepatobiliary disorders, no distinction between different disease groups could be made based solely on FSBA and PSBA. FSBA and PSBA were found to be relatively sensitive and specific parameters compared to the other hepatic tests. PSBA tended to be superior to the other parameters investigated in terms of sensitivity, specificity, positive predictive value, and negative predictive value. PMID- 1907784 TI - Effects of temperature, pH and blood storage on osmotic fragility of duck erythrocytes. AB - The osmotic fragility of duck erythrocytes at different pH and temperatures and during blood storage was studied. The fragility increased in acidic solution and also as the temperature increased. However, storage of blood decreased the fragility of duck erythrocytes. PMID- 1907783 TI - Pharmacokinetics of ticarcillin and ticarcillin-probenecid in sheep. AB - Serum concentrations of ticarcillin were measured serially over a period of 12h in a cross over trial involving 6 healthy adult ewes after intravenous and intramuscular (IM) administration of 40 mg ticarcillin per kg body weight. Probenecid (40 mg/kg) was also administered IM immediately before the IM administration of 40 mg/kg ticarcillin. Pharmacokinetic values after intravenous administration were: half-life of elimination (T 1/2 beta) = 0.90 +/- 0.09 h; volume of distribution at steady state (Vdss) = 456.8 +/- 106.6 ml/kg, total body clearance (CIB) = 614.5 +/- 81.2 ml/h/kg. Ticarcillin persisted in serum at greater than or equal to 1.5 micrograms/ml for 4 hours. Pharmacokinetic and bioavailability values after intramuscular administration were: half-life of absorption (T 1/2 ab) = 8.08 +/- 1.98 min; T 1/2 beta = 0.96 +/- 0.07 h. Peak serum concentration (Cmax) was 31.11 +/- 6.02 micrograms/ml at 0.50 h (Tmax), bioavailability (F) was 0.82 +/- 0.09. After ticarcillin was administered IM together with probenecid the T 1/2 ab was 33.9 +/- 13.7 min, the T 1/2 beta 2.66 +/- 0.65 h, Cmax = 44.87 +/- 5.58 at 1.33 +/- 0.44 h, and F = 1.25 +/- 0.23. PMID- 1907785 TI - The inhibition of the reticular groove reflex in sheep by clonidine. AB - Intravenous clonidine, an alpha-2 adrenoreceptor agonist, at 2 micrograms.kg-1 and 4 micrograms.kg-1, inhibited the activation by oral copper sulphate of the reticular groove reflex in adult sheep. The plasma concentration of xylose after oral dosing was used as an indicator of groove activation. The inhibition was prevented by prior injection of an alpha-2 antagonist, idazoxan. Indirect evidence of prolongation of intestinal transit time was found with the lower dose of clonidine. Idazoxan injected alone appeared to increase the absorption of xylose. PMID- 1907786 TI - Concentrations of nuclear progesterone receptors in endometrium of virgin and repeat breeder heifers after embryo transfer. AB - The present study aimed to correlate the repeat breeder syndrome in the bovine with an impaired or suboptimal uterine progestational response. Concentrations of nuclear (i.e. transformed) receptors for progesterone (PRn) were determined with a binding and exchange method in endometrial samples from virgin (VH) and repeat breeder (RBH) heifers 15 days post oestrus. The heifers were recipients of Day 7 demi-embryos collected from donors with normal fertility and transferred 8 days prior to tissue sampling. Results were compared with both the type of heifer, the condition of the embryo present within the uterus and the temporal relationship to the hormone plasma levels. The binding data for PRn indicated that a single class of high-affinity, low-capacity sites existed. The amount of PRn in VH endometria holding embryonic structures was significantly greater than in RBH, but no statistical differences were found in their plasma progesterone levels. PRn concentrations were also higher in the uterine horn in which an elongated (greater than 15 mm), morphologically normal embryo was present, when compared to cornua with small (less than 5 mm) embryos, regardless of recipient group. Furthermore, in endometria with an elongated embryo in the lumen, the relative amount of PRn was significantly greater in VH than in RBH. The present results indicate that the RBH recipients of Day 7 demi-embryos by Day 15 have fewer numbers of specific receptors for maternal progesterone, which could explain in part the poorer development of the transferred embryos compared with that in virgin heifers. PMID- 1907787 TI - In vivo fertilizing capacity of deep frozen boar semen packaged in plastic bags and maxi-straws. AB - Pooled ejaculates from six fertile boars were frozen under controlled conditions in Teflon FEP-film plastic bags (5 ml) and maxi-straws (2.5 ml) using 3% glycerol as cryoprotectant. The percentages of both post-thaw motility and normal apical ridges were significantly higher (P less than 0.001) for the bags (54.5 and 75%) than for the maxi-straws (40.1 and 59.4%) respectively. For evaluation of the in vivo fertilizing capacity of the frozen-thawed spermatozoa, 26 gilts were inseminated once 24 h after the first observation of standing reflex in their second oestrus, with 5 ml of semen (containing 5 billion spermatozoa) reconstituted in 80 ml of BTS from either bags or maxi-straws. Ova were recovered from the oviducts/uteri 2-4 days following insemination and examined for cleavage and sperm binding to the zona pellucida (ZP). Significantly higher rates (P less than 0.02) of fertilized ova were found in the bag-inseminated (75%) than in maxi straw inseminated gilts (63%); and similarly their ova had significantly more spermatozoa in the ZP, irrespective of whether they were fertilized or nonfertilized. This study confirmed that the plastic bags are suitable and may be used for packaging single insemination doses of deep frozen boar semen for routine A.I. work. PMID- 1907788 TI - Statistical evidence for a link between bronchopneumonia and disseminated focal nephritis in pigs. AB - An investigation on the occurrence of different pneumonia types and their possible concurrence with other pluck organ disorders was made on 6,565 pigs presented at slaughter. The frequency of disseminated focal nephritis in a bronchopneumonia group and a non-bronchopneumonia residual group, respectively, was found to differ significantly from the mean frequency of nephritis in all pig plucks examined. The number of lesioned kidneys in each of 28 samples contributing to the bronchopneumonia group and in each of 8 samples contributing to the residual group was regressed group-wise on the number of individual plucks examined in each sample; the correlation coefficient for each of these two groups was calculated. These calculations showed a highly significant link between bronchopneumonia and disseminated focal nephritis. The histopathological and bacteriological examination of some lung and kidney lesions representing the bronchopneumonia group substantiated this finding. It is concluded that the two diseases are connected through dissemination, and that Pasteurella multocida is the organism involved in the majority of cases. PMID- 1907789 TI - Gross, microscopic and ultrastructural lesions of protoporphyria in Limousin calves. AB - The gross, microscopic and ultrastructural lesions associated with the genetic disease, protoporphyria, in Limousin cattle were studied in detail. The clinical signs and lesions were most severe in young animals. In the liver, the lesions consisted of portal fibroplasia, bile ductule hyperplasia, parenchymal cell swelling, and pigment accumulation. Maltese cross-like crystals were evident under polarized light. Ultrastructurally, there were large secondary lysosomes comprised of electron-dense granules associated with lipid droplets in hepatocytes. Phagocytic cells in the dermis also contained large heterogeneous secondary lysosomes. PMID- 1907790 TI - [The pathology and pathogenesis of experimental Mycoplasma hyorhinis infection of piglets with and without thermomotoric stress. 1. Pathologico-anatomic, histologic and immunomorphologic study results]. AB - The effect of an experimental Mycoplasma (M.) hyorhinis infection (3 times intranasal instillation of 3-5 ml bouillon with 10(7) Colony forming units [CFU]/ml) in combination with a standard thermomotoric stress (swim-test) was studied in piglets using pathomorphological, immunomorphological and microbiological methods. The 92 piglets were divided into the following 5 groups: swimmers with infection (S-I; n = 19); swimmers without infection (S; n = 19); control piglets with infection (K-I; n = 21); controls without infection, but direct (K1; n = 16) or indirect contact (K2; n = 17) with experimentally infected animals. The experimental or spontaneous infection (direct or aerogenous infection) with M. hyorhinis caused in 30.4% of the piglets an acute or subacute, catarrhal-purulent bronchopneumonia with an interstitial component. Incidence and intensity of pneumonia were significantly higher in the groups with thermomotoric stress (independent from the mode of infection) than in the non-stressed groups. The M. hyorhinis pneumonia was characterized by a limited expansion and a trend to restitution. The causal agent (M. hyorhinis) was demonstrated with immunomorphological methods (immunofluorescence and PAP) in the ciliary zone of the nasal, tracheal and especially on the bronchial mucosa, and occasionally in the bronchioles and alveoli. PMID- 1907791 TI - [The epidemiology of neonatal meningitis]. AB - The epidemiological features of meningitides in newborns have been studied and criteria making it possible to distinguish the cases of intrauterine and postnatal infection have been proposed. The overwhelming majority of these infections has been found to occur due to hospital infections caused by enterobacteria and nonfermenting bacteria. In meningitides of this etiology the sources of infection are newborns colonized by these microorganisms. Infection is transmitted through everyday contacts through the hands of the medical staff. Besides, moist environmental objects serve as the additional reservoir of infection. PMID- 1907792 TI - [A radioimmunological method for determining IgA-class antimeningococcal secretory antibodies in human saliva]. AB - The data on the content of secretory IgA antibodies to group A Neisseria meningitidis protein antigen in the saliva of persons, both having had contact with N. meningitidis culture and having had no such contact, are presented. The results were obtained by the method of radioimmunoassay, developed specially for the determination of N. meningitidis protein antigen. PMID- 1907793 TI - [The protective activity of 2 normal immunoglobulin preparations for intravenous administration in experimental Pseudomonas aeruginosa infection]. AB - The antibody levels in 18 batches of the preparations of human immunoglobulin, Immunovenin and Immunovenin-Intact, for intravenous injection were determined in the enzyme immunoassay with the use of the mixture of P. aeruginosa lipopolysaccharide antigens of seven immunotypes. The average antibody titers in these preparations were identical. The preparations were found to have protective action against P. aeruginosa experimental infection in mice. PMID- 1907794 TI - Distributions of fibronectin, laminin, type I and IV collagens and carbonic anhydrase isozyme III during bovine ruminal epithelial development. AB - The present study describes the immunohistochemical distributions of extracellular matrices and the carbonic anhydrase isozyme III (CA-3) in the bovine ruminal epithelium during fetal development. Fibronectin (FN), laminin and type I and IV collagens were distributed in the ruminal subepithelial mesenchymal regions with nonspecific regionality during the gestational periods. At stages after about 59 cm crown-rump length (CRL), FN of the epithelial basement membrane disappeared, and CA-3 appeared in the basal epithelial cells of the root of the ruminal papillae, suggesting that the functional differentiation of the ruminal epithelium might start at around 59 cm CRL in bovine fetuses. PMID- 1907796 TI - Exocytosis in pheochromocytoma cells after exposure to a high concentration of potassium. AB - An electron-microscopic study revealed exocytosis of electron-dense granules in rat pheochromocytoma (PC12) cells after 1-min exposure to a high concentration of potassium medium. Numerous omega profiles indicative of the exocytosis were seen in the surface membrane of the PC12 cells. Most omega profiles showed clear or did not contain the granule contents. Sometimes, the granular, flocculent or dense materials were seen within the omega profiles that were exposed directly to the extracellular medium. Moreover, noncoated or coated omega profiles were observed. Coated vesicles were also visible under the surface membrane. The present study suggests that PC12 cells retain the exocytotic release mechanism for catecholamines. PMID- 1907795 TI - Isolation and culture of human decidual capillary endothelial cells in serum-free medium supplemented with human uterine angiogenic factor. AB - Human decidual capillary endothelial (HDCE) cells, obtained from decidual fragments of legally induced first-trimester terminations of pregnancies, were cultured in a serum-free medium supplemented with human uterine angiogenic factor (HUAF). The method of isolating the cells from the decidual tissue is described. Identification of the decidual endothelial cells was based on light- and electron microscopic observations as well as on antifactor VIII immunoperoxidase-staining technique. The HDCE cell culture in the serum-free medium lasted for 25 weeks through eight subcultures. The cells frozen in glycerin yielded 80% viability after thawing. Electron-microscopic observations of the monolayer demonstrated Weibel-Palade bodies, desmosomes and tight junctions. HUAF is mitogenic to HDCE at 10-100 ng/ml. The dependency of HDCE cells grown in culture on HUAF may explain in part the mechanism involved in the dynamic vascular expansion occurring during gestation. PMID- 1907797 TI - A correlative study of the freezing patterns in rat myocardium using scanning and transmission electron microscopes. AB - Rat myocardial tissue, both fresh and chemically fixed, was quench frozen in melting Freon 22 at rates that resulted in in the formation of large ice crystals. The material was studied with both scanning and transmission electron microscopy. Particular attention was paid to the characteristic freezing patterns within the myofibrils and mitochondria, and to features exposed by such freezing that might otherwise remain obscured. The freezing patterns found in tissue subjected to different processes were compared with the ultrastructure of unfrozen, chemically fixed counterparts. Ice-crystal cavities in the contractile material varied considerably along the length of a given myofiber in which the freezing front had progressed in parallel with the long axis of the myofibers. It is suggested that the intercalated disc functioned as a barrier to the freezing process. Ice generally compressed and distorted the contractile material beyond recognition, although the positions of the Z-bands remained evident and in register. Most single-fixed mitochondria were devoid of visible ice-crystal cavities, and the cristae generally remained intact. On the other hand, ice crystal cavities were commonly seen between cristae of double-fixed mitochondria. No signs of perforations were seen in lipid bilayer membranes. Numerous strand like connections between mitochondria as well as between mitochondria and the myofibrillar surface, which were believed to be sarcotubules, were made visible by the slow freezing process. Other strands, transverse to the myofibrils, connecting adjacent Z-bands and joining Z-bands to the sarcolemma, were interpreted as cytoskeletal elements. These strands, together with what apparently were SR tubules, exhibited high resistance to the stresses associated with the formation of ice-crystals. PMID- 1907798 TI - [Unilateral heterotropia of the cerebral cortex]. AB - The case of a slight epileptic 30-year-old woman with heterotopic gray matter diagnosed by TC and NMR is described. The seizures of left jacksonian type begun at the age of 3, and stopped at the age of 12. In 1986 the seizures of atonic akinetic type reappeared and continued until now at an average of 2 for year without obstacle for her job of employer. Cerebral computed tomography and magnetic resonance imaging showed a neuronal migration anomaly with nodular masses of gray matter in the right temporo-parietal area, characteristic image of gray matter heterotopia. PMID- 1907799 TI - Pyruvate dehydrogenase deficiency due to a 20-bp deletion in exon II of the pyruvate dehydrogenase (PDH) E1 alpha gene. AB - A 20-bp deletion in the last exon of the pyruvate dehydrogenase (PDH) E1 alpha gene was found in a severely affected female patient diagnosed with PDH deficiency. PDH-complex activity in the patient's fibroblasts was 22% of that in normal controls. The mutation was characterized using PCR techniques with both patient cDNA and genomic DNA, followed by sequencing of the products. E1 beta cDNA sequence was found to be the same as that in controls. The deletion causes a frameshift and the occurrence of a premature stop codon. Western blot analysis revealed an extra band migrating just above the PDH E1 beta band. Northern blot analysis showed normal levels of both E1 alpha and E1 beta message when probed with the respective cDNAs. However, a larger intermediate-size transcript was observed for this patient in the E1 beta blot. The 20-bp deletion was not found in either parent's genomic DNA, and hence we conclude that the mutation must have occurred de novo, either in the germ-line cells or immediately following fertilization. PMID- 1907801 TI - Utility of a transdermal delivery system for antihypertensive therapy. Part 1. AB - A retrospective evaluation of patient-level Medicaid claims data from two states was undertaken to discern the fiscal utility of transdermally delivered clonidine versus both the oral formulation of clonidine and oral formulations of eight other antihypertensive agents. In the first phase of our two-part study, we compared paid claims data (n = 1,135) from Florida for transdermal and oral clonidine. Multivariate regression analysis was used to evaluate the incremental impact of six variables on health-care expenditures in the first year after patients were given a diagnosis of hypertension. These variables were: age, gender, prior utilization of medical services, regimen complexity, and dosage formulation. Patients prescribed transdermal clonidine experienced a significant (p less than or equal to 0.001) increase in prescription expenditures and significant reductions in the use of physician (p less than or equal to 0.05), laboratory (p less than or equal to 0.10), and hospital (p less than or equal to 0.05) services. Moreover, savings were maximized (p less than or equal to 0.001) where multi-drug regimens incorporated the transdermal delivery system. In the second phase of our study we compared paid claims data (n = 8,894) from South Carolina for transdermal clonidine and for nine oral antihypertensive agents: atenolol, captopril, clonidine, diltiazem, enalapril, metoprolol, prazosin, terazosin, and verapamil-SR. Once again, regression analysis was used, this time to evaluate the incremental impact of five variables on health-care expenditures in the first year post diagnosis: age, gender, prior utilization of medical services, regimen complexity, and Medication Possession Ratio (MPR), an index of compliance. The data from part 2 of our study revealed that patients assigned a b.i.d. oral antihypertensive agent experienced a significant reduction (p less than or equal to 0.05) in MPR and a significant (p less than 0.05) increase in health-care expenditures when compared to patients prescribed the transdermal delivery system and to patients prescribed once-daily oral medications. These data confirm previous findings concerning the impact of complicated dosing regimens on compliance in hypertensive patients. In this two-part paper we report the data from both phases of our study. PMID- 1907800 TI - Human beta-galactosidase gene mutations in GM1-gangliosidosis: a common mutation among Japanese adult/chronic cases. AB - Molecular analysis of the human beta-galactosidase gene revealed six different mutations in 10 of 11 Japanese GM1-gangliosidosis patients. They were the only abnormalities in each allele examined in this study. A 165-nucleotide duplication (positions 1103-1267) was found in two infantile patients, producing an abnormally large mRNA; one patient was probably a homozygote, and the other was a heterozygote of this mutation. The other two infantile patients had different mutations; a 123 Gly(GGG)----Arg(AGG) mutation in one patient and a 316 Tyr(TAT)- --Cys(TGT) mutation in the other. A 201 Arg(CGC)----Cys(TGC) mutation, eliminating a BspMI site, was detected in a late-infantile/juvenile patient; the restriction-site analysis of amplified genomic DNA confirmed his heterozygosity for this mutation. A 51 Ile(ATC)----Thr(ACC) mutation was found in all five adult/chronic patients examined in this study. It created a SauI site, and restriction-site analysis confirmed that four patients were homozygous mutants. The other was a compound heterozygote for this mutation and another 457 Arg(CGA)- --Gln(CAA) mutation. These mutant genes expressed markedly decreased or completely deficient enzyme activities in beta-galactosidase-deficient human fibroblasts transformed by adenovirus-SV40 recombinants. We conclude that gene mutations are heterogeneous in GM1-gangliosidosis but that the 51 Ile(ATC)--- Thr(ACC) mutation is common among the Japanese adult/chronic cases. Genotype phenotype correlations in GM1-gangliosidosis are briefly discussed. PMID- 1907802 TI - Utility of a transdermal delivery system for antihypertensive therapy. Part 2. PMID- 1907803 TI - Small area analysis of hospital discharges for musculoskeletal diseases in Michigan: the influence of socioeconomic factors. AB - PURPOSE: The rise in health care costs has occasioned a number of initiatives in an attempt to reduce the rate of increase. Despite the growth of health maintenance organizations and preferred provider organizations and the introduction of Medicare's prospective payment system, health care costs have continued to increase. Coincident with these efforts, a number of researchers have shown that there exists wide variation in age-adjusted hospital discharge rates, which translate into significant variation in per capita expenditures. Much of the focus on the reasons for hospital admission variability has been on physician practice variation. If most of the variation in hospital discharge rates is due to physician practice style, then payment systems can be developed (e.g., capitation) that limit physician practice variation without harming patients. We examined socioeconomic factors in Michigan communities to assess their association with hospital discharge rates for patients with musculoskeletal diseases. PATIENTS AND METHODS: Data on hospital discharges from 1980 and 1987 were taken from the Michigan Inpatient Data Base. All admissions from the major diagnostic category 8, diagnosis-related group (DRG) 209-256 were included. Zip code-specific hospitalization data were grouped into small geographic areas or hospital market communities (HMCs). Discharge rates were calculated, and profiles of the socioeconomic characteristics of each of the HMCs were developed. A Poisson regression model with an extrasystematic component of variance was used to analyze the association of HMC socioeconomic characteristics with age-adjusted hospital use. RESULTS: We found that four socioeconomic variables, average annual income per capita, percent of the population with four years of college, percent of the population living in an urban area, and percent of families with incomes below the poverty line, explained 26.6% (R2) of the variation in overall hospital discharge rates (p less than 0.001). Moreover, we found that the ability of the model to explain variability was influenced by the type of disease, and that these socioeconomic variables had a consistent effect across the range of DRGs. Finally, we noted that, over the period of 1980 to 1987, socioeconomic factors remained important in explaining hospital use despite the dramatic changes in the delivery of care over this period. CONCLUSION: Socioeconomic factors play a significant role in explaining the observed variation in hospital discharge rates for musculoskeletal diseases. Models utilizing only physician practice variation to account for the population-based differences in discharge rates are overly simplistic. In order to ensure that vulnerable subsets of the population are not harmed by the introduction of cost-containment strategies based on simplistic models, more attention must be paid to the socioeconomic and epidemiologic factors related to hospital use. PMID- 1907804 TI - Prenatal lesions in an ovine fetus with GM1 gangliosidosis. AB - Sheep affected with ovine GM1 gangliosidosis are normal at birth and develop clinical signs, initially ataxia, commencing at approximately 5 months of age, which progresses rapidly to recumbency. Superovulation and embryo transfer techniques were applied to a flock of carrier sheep of ovine GM1 gangliosidosis to increase the numbers of carrier and affected animals. A recipient ewe with 3 at-risk fetuses died at 4 months of gestation (normal ovine gestation is 5 months), and spectrofluorimetric assay of cerebral lysosomal beta-galactosidase of the fetuses showed that 2 were carriers and one was an affected fetus. The affected fetus had marked cytoplasmic enlargement and vacuolization of central and peripheral nervous system neuronal soma and of hepatocytes and renal epithelial cells. Lectin histochemistry indicated abnormal storage of complex carbohydrates, with terminal saccharide moieties consisting of beta-galactose, N acetylneuraminic acid, and N-acetylgalactosamine. This case underlines the need for prenatal initiation of therapy and also demonstrates that vacuolization alone is not the cause of clinical signs in this lysosomal storage disease in that clinical signs do not commence until at least 5 months after vacuolization is histologically apparent. PMID- 1907806 TI - Injuries among young soccer players. AB - We registered all new injuries among 496 male youth soccer players, aged 12 to 18 years, during the course of one year. The incidence of injury was 3.7 injuries per 1000 hours of soccer per player. The incidence increased with age, and at the higher ages within the youth players, approached the incidence rate of senior players (age greater than or equal to 18 years). Seventy percent of the injuries were located in the lower extremities, particularly the knee (26%) and ankle (23%). Back pain occurred in 14% of players. Fractures, which accounted for 4% of injuries, were most often in the upper extremities. We conclude that youth soccer is a relatively low-risk sport with an injury pattern that differs slightly from that of senior players. PMID- 1907805 TI - Hyperexpression of interferon-gamma-induced MHC class II genes associated with reorganization of the cytoskeleton. AB - Class I and class II major histocompatibility complex (MHC) gene products are key recognition units in the induction and regulation of the immune response. Expression of class I and class II may be constitutive or inducible by cytokines such as interferon-gamma (IFN-gamma). A key step in the induction of MHC genes is recognition of IFN-gamma by its membrane receptor. The work described here examines the regulation of the occupied IFN-gamma receptor by the cytoskeleton. To do this the authors have used the fungal metabolites dihydrocytochalasin B (DHCB) and cytochalasin D (CD), substances that bind to actin filaments and thereby disrupt the cytoskeleton. The authors have studied the effect of DHCB and CD on IFN-gamma-induced MHC gene expression in 143 B cells, a human osteosarcoma derived cell line. Herein the authors demonstrate that alterations in the cytoskeleton induced by DHCB and CD can lead to increases in IFN-gamma-induced MHC gene expression. Dihydrocytochalasin B added up to 3 hours after IFN-gamma results in a threefold to sixfold increase in levels of class II mRNA while producing minimal enhancement of class I gene expression. In contrast, glyceraldehyde-3-phosphate dehydrogenase mRNA expression was unaltered by IFN gamma or by the cytochalasins. The increased amount of class II mRNA can be accounted for by a concomitant increase in transcription rate of this gene. Studies using 125I-IFN-gamma demonstrate that the occupied IFN-gamma receptor associates with a Triton X-100 insoluble fraction of 143 B cells and that DHCB and CD markedly inhibit this association. The results described here provide evidence that is consistent with the hypothesis that the activity of the occupied IFN-gamma receptor may be modulated by interactions with the cytoskeleton of the cell. This receptor may be one of a group of plasma membrane receptors that are sensitive to the action of cytochalasins after ligand binding. PMID- 1907807 TI - Syndesmotic ankle sprains. AB - In this study we reviewed ankle sprains in a professional football team over a 6 year period. Fifteen players who sustained syndesmotic ankle sprains were compared with 28 players who sustained significant lateral ankle sprains. Players with syndesmotic sprains missed significantly more games and practices and they received substantially more treatments than players with lateral ankle sprains. Physical examination findings, results of radiographic evaluations, and etiologic factors are discussed. The external rotation stress test, a clinical method for diagnosis of this type of sprain at the time of injury, is described. Results of this study clearly demonstrate a prolonged recovery time for syndesmotic ankle sprains. Physicians and trainers who are aware of this injury can differentially diagnose these two types of sprains in the early postinjury period by the method described. PMID- 1907808 TI - Schistosoma mansoni tropomyosin: production and purification of the recombinant protein and studies on its immunodiagnostic potential. AB - A cDNA that encodes Schistosoma mansoni tropomyosin, except for 10 amino acids at the amino terminus, has been cloned into a pOTSNCO plasmid vector. Induced expression resulted in a constant level of recombinant protein production. The recombinant S. mansoni tropomyosin was purified from preparative SDS-PAGE gel and by a combination of 20% ammonium sulfate fractionation and fast protein liquid chromatography-ion-exchange chromatography. The purified recombinant S. mansoni tropomyosin was tested as an immunodiagnostic reagent in Western blot and enzyme linked immunosorbent assays. Sera from individual patients with chronic S. mansoni infection, but not S. haematobium, S. japonicum, parasitic infections other than schistosomiasis, and without infection reacted with the recombinant tropomyosin. The species specificity of S. mansoni tropomyosin suggests that further study of its potential as an immunodiagnostic reagent is warranted. PMID- 1907809 TI - Inhibitory activity against Plasmodium vivax sporozoites induced by plasma from Saimiri monkeys immunized with circumsporozoite recombinant proteins or irradiated sporozoites. AB - Two Saimiri monkey vaccine trials have been conducted comparing four recombinant Plasmodium vivax circumsporozoite proteins and irradiated sporozoites. Only a small number of animals immunized with certain recombinants or irradiated sporozoites became fully protected against sporozoite challenge. Preimmunization and postimmunization plasma samples obtained from 30 monkeys on the day of challenge were tested in an in vitro assay based on sporozoite development into exoerythrocytic stages in primary cultures of Saimiri monkey hepatocytes. The percentage of inhibition was determined by comparison of the number of exoerythrocytic stages developing from sporozoites preincubated with a preimmunization and a postimmunization plasma sample of each animal. The plasma samples of the day of challenge of nearly all the immunized animals had a variable, but significant inhibitory effect, when compared with the corresponding preimmunization sample. We found no correlation between the degree of in vitro inhibition of liver stage development, and the in vivo protection against sporozoite challenge of individual animals. The variable results of the incubation of sporozoites with "normal" plasma of different animals indicates that the in vitro results were affected by plasma factors unrelated to anti sporozoite antibodies. PMID- 1907811 TI - Flow injection analysis of lactose using covalently immobilized beta galactosidase, mutarotase, and glucose oxidase/peroxidase on a 2-fluoro-1 methylpyridinium salt-activated Fractogel support. AB - Milk samples were analyzed for their lactose content using flow injection analysis and incorporating immobilized beta-galactosidase or beta galactosidase/mutarotase and glucose oxidase/peroxidase bioreactors. These enzymes were immobilized, under mild conditions, on to a 2-fluoro-1 methylpyridinium salt-activated Fractogel support. The use of a phosphate buffer (0.15 M) was found to facilitate the rapid mutarotation of alpha-D-glucose and hence could obviate the need for the more expensive mutarotase. The chromogenic agents of choice for monitoring the reaction were 3-methyl-2-benzothiazolinone hydrazone and 3-dimethylaminobenzoic acid. Linearity was observed over the concentration range 16-160 micrograms/ml using lactose standards (r = 0.996). Between 30 and 40 milk samples/h can be analyzed. Comparisons are made with existing HPLC and alkaline methylamine methods for a range of milk matrices. The FIA method consistently gives the lowest standard deviations and coefficient of variation for the various milk matrices analyzed. PMID- 1907810 TI - [A clinical score system for children with ARDS]. AB - In a retrospective study we developed a simple acute respiratory distress syndrome (ARDS) scoring system in order to analyze the severity of ARDS as precisely as possible. From March 1983 to May 1990, 17 children with ARDS were admitted and treated at the pediatric intensive care unit of the University Hospital of Graz. The ARDS score was evaluated as a predictor of outcome. The score is based on four variables: mean airway pressure, oxygenation index, additional number of organ system failure and a radiological score, each of which was assigned a score between 0 and 3 (Table 3). The score was recorded on admission or immediately after respiratory failure and after 24, 48 and 72 h. The patients were divided into survivors and non-survivors. After 24 h of mechanical ventilation the ARDS score was 7.16 +/- 0.79 in survivors and 10.4 +/- 0.4 points in non-survivors (P less than 0.0006). Similar differences were found after 48 and 72 h of therapy. In addition, the predictive power of the ARDS score after 24 h was tested at a level of 8 points. The sensitivity and the positive predictive value were 90%, while specificity and negative predictive value were 85.7%. The correct prediction was 88.2%. We conclude that this simple ARDS score can be an useful prognostic factor in patients with ARDS. PMID- 1907812 TI - Immobilized artificial membrane chromatography: rapid purification of functional membrane proteins. AB - A solid-phase membrane mimetic system, denoted as immobilized artificial membranes (IAM), has been developed and utilized as a novel high-performance liquid chromatography (HPLC) matrix for the first step in the rapid purification of functional membrane proteins. IAM phases consist of monolayers of amphiphilic membrane lipid molecules covalently bonded to a rigid silica particle. These monolayers of lipids have proved remarkably effective for the chromatography of biomolecules. Several cytochrome P450 isozymes, an extremely important family of hydrophobic membrane proteins with a labile heme catalytic center, have been partially purified in functional conformations from rat liver, kidney, and adrenal microsomes on IAM supports. Functionality of purified P450 and P450 reductase has been demonstrated by optical difference spectroscopy, by carbon monoxide binding, and by reconstitution of enzymatic activity in vitro. Other membrane proteins, including rat liver plasma membrane NADH oxidase and ferricyanide oxidoreductase have also been partially purified by IAM HPLC. The methods for purification of these proteins are described. PMID- 1907814 TI - Bioassay for siderophore utilization by Candida albicans. AB - A convenient plate assay which is sensitive to medium pH has been developed to evaluate potential siderophores of Candida albicans. Adding a siderophore to a filter paper disk on chemically defined Lee's agar (final pH 7.2) seeded with the test strain reversed the growth inhibitory effects of the supplemented (25-100 micrograms/ml) iron chelator ethylenediaminedi(o-hydroxyphenylacetic acid), to provide a zone of growth stimulation. This bioassay has been used to demonstrate the structure-activity relationships of ferrichrome and several water-soluble hydroxamate peptide building blocks of this natural siderophore. Of all compounds so evaluated, ferrichrome exhibited the best activity. PMID- 1907813 TI - A solid-phase assay for beta-1,4-galactosyltransferase activity in human serum using recombinant aequorin. AB - We have developed a sensitive and rapid solid-phase assay for the serum enzyme UDPGal:beta-D-GlcNAc beta-1,4-galactosyltransferase (beta 1,4-GT) (EC 2.4.1.38) that employs the recombinant bioluminescent protein aequorin as the enzyme label for product detection. The substrate for beta 1,4-GT is a neoglycoprotein, bovine serum albumin containing covalently attached GlcNAc residues (GlcNAc-BSA), and it was immobilized by adsorption in microtiter plate wells. Serum samples were added to each well along with saturating levels of UDPGal and Mn2+. Galactosylation of the neoglycoprotein acceptor by the serum beta 1,4-GT produces the N acetyllactosamine derivative Gal beta 1, 4GlcNAc-BSA. The product formed is quantified by adding the biotinylated plant lectin Ricinus communis agglutinin-I, which binds specifically to N-acetyllactosamine, followed by the addition of streptavidin and the biotinylated aequorin. Aequorin produces a flash of light in response to Ca2+ and is detectable to 10(-19) mol in a luminometer. Using this assay, the beta 1,4-GT activity in human serum and the activity of a semipurified beta 1,4-GT are linear with time and serum concentration over a wide range. The reaction is dependent on UDPGal and Mn2+, is highly reproducible with a low background, and can be performed in a few hours. Assays employing aequorin have a wider range of linearity than those employing horseradish peroxidase as an enzyme label. These results demonstrate that the assay for beta 1,4-GT is useful for determining activity in heterogeneous samples and also demonstrate the utility of the recombinant protein aequorin for solid-phase assay methods. PMID- 1907815 TI - A method for preparing skeletal muscle fiber basal laminae. AB - Previous attempts to prepare skeletal muscle basal laminae (BL) for ultrastructural analyses have been hampered by difficulties in successfully removing skeletal muscle proteins and cellular debris from BL tubes. In the present study we describe a two phase method which results in an acellular muscle preparation, the BL of which are examined by light, transmission electron, and scanning electron microscopy. In the first phase, excised rat extensor digitorum longus muscles are subjected to x-radiation and then soaked in Marcaine to inhibit muscle regeneration and to destroy peripheral muscle fibers. The muscles are then grafted back into their original sites and allowed to remain in place 7 14 days to allow for maximal removal of degenerating muscle tissue with minimal scar tissue formation. In the second phase, the muscle grafts are subjected sequentially to EDTA, triton X-100, DNAase, and sodium deoxycholate to remove phagocytizing cells and associated degenerating muscle tissue. These procedures result in translucent, acellular muscle grafts which show numerous empty tubes of BL backed by endomysial collagenous fibers. These preparations should be useful for morphological analyses of isolated muscle BL and for possible in vitro studies by which the biological activity of muscle BL can be examined. PMID- 1907816 TI - Modifications by halothane of responses to acute hypoxia in systemic vascular capacitance, resistance, and sympathetic nerve activity in dogs. AB - To examine the effects of halothane on segmental vascular responses to hypoxia, we used cardiopulmonary bypass with venous outflow divided into three compartments (splanchnic, coronary, and "other") in dogs anesthetized with pentobarbital sodium. The reservoir volume changes represented the inverted changes in systemic blood volume (SBV). In addition, sympathetic efferent nerve activity (SENA) was simultaneously recorded from the ventral ansa subclavian nerve. Experiments were done in two groups: severe hypoxia (PO2 of 19 mm Hg) and moderate hypoxia (PO2 of 50 mm Hg). Hypoxia provoked a significant decrease in SBV of 22.3 +/- 3.1 mL/kg and 10.5 +/- 1.6 mL/kg during severe and moderate hypoxia, respectively. Two percent end-tidal halothane attenuated the decrease in SBV to 10.3 +/- 1.3 mL/kg during severe hypoxia, and 1% halothane attenuated the decrease to 3.7 +/- 1.4 mL/kg during moderate hypoxia. Subsequent chemoreceptor denervation in the presence of 1% halothane completely abolished the moderate hypoxia-induced decrease in SBV. In the presence of halothane, vascular resistance during hypoxia was significantly less than that during control conditions. Sympathetic efferent nerve activity increased significantly during severe and moderate hypoxia by about 180% and 55%, respectively. During severe hypoxia, halothane did not cause any change in the response of SENA, whereas during moderate hypoxia, halothane tended to decrease SENA, but not significantly, and subsequent chemoreceptor denervation completely abolished the increase in SENA. Coronary resistance showed a hypoxia-induced reduction that was not influenced by halothane. These results suggest that acute hypoxia causes a decrease in SBV dependent on the severity of hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1907817 TI - Reliability of capnography in identifying esophageal intubation with carbonated beverage or antacid in the stomach. AB - To evaluate the reliability of capnography in identifying esophageal intubation in the presence of a carbonated beverage in the stomach, we first investigated the amount of CO2 released from different carbonated beverages and antacids in a simulated stomach; next we measured the end-expired CO2 level during esophageal ventilation with a carbonated beverage in the stomachs of six swine. CO2 levels of approximately 20% were consistently observed in all carbonated beverages. The CO2 levels obtained with sodium bicarbonate, Maalox, and sodium citrate were 19.3%, 2.0%, and 0%, respectively. CO2 waveforms were observed during esophageal ventilation in five of six animals after intragastric administration of a carbonated beverage. An end-expired CO2 level of 2.5% or more was observed in two swine. The highest end-expired CO2 level measured was 5.3%. We conclude that although capnography is convenient and effective, it lacks all the attributes of an ideal monitor for detecting esophageal intubation. PMID- 1907818 TI - Reflection of CO2 laser radiation from laser-resistant endotracheal tubes. AB - To assess the possibility of indirect damage by CO2 laser reflection from specialized or modified tracheal tubes, four different tracheal tubes were studied. They were (1) a Rusch red rubber tracheal tube wrapped with 3M No. 425 aluminum foil tape, (2) a Rusch red rubber tracheal tube wrapped with Venture copper foil tape, (3) a polyvinylchloride tracheal tube wrapped with Laser-Guard protective coating, and (4) a Mallinckrodt Laser-Flex tracheal tube. The tracheal tubes were straightened and centered within cardboard cylinders and the laser set to 40 W was aimed to reflect from the tracheal tubes onto the cardboard. The times to combustion perforating the cardboard cylinders because of laser reflection were 1.41 +/- 0.54 (mean +/- SD), 1.73 +/- 0.93, 3.70 +/- 2.18, and 9.26 +/- 3.40 s for tracheal tubes 1, 2, 3, and 4, respectively. The differences between the times to combustion with tracheal tubes 3 and 1, 3 and 2, 4 and 1, 4 and 2, and finally, 4 and 3 were statistically significant. We conclude that the Laser-Guard-wrapped polyvinylchloride tracheal tube and the Mallinckrodt Laser Flex tracheal tube were less reflective of incident CO2 laser radiation than the copper or aluminum-foil-wrapped red rubber tracheal tubes. PMID- 1907820 TI - [Bladder bilharziasis: report of a case]. AB - Herein we describe a case of vesical bilharziasis in a Spanish patient who became infected during a trip to an endemic area. The characteristic features of the disease and particularly its relationship to squamous type bladder tumors are discussed with a special focus on treatment with Praziquantel. PMID- 1907819 TI - Differential toxinogenesis in the genus Pichia detected by an anti-yeast killer toxin monoclonal antibody. AB - The differential toxinogenesis of 25 isolates belonging to species of the potential yeast killer genus Pichia that were previously classified in the genus Hansenula was comparatively demonstrated by two serologic techniques (indirect immunofluorescence and double immunodiffusion) by using a monoclonal antibody against a yeast killer toxin produced by a selected strain of Pichia anomala (UCSC 25F). The killer phenotypes of the Pichia isolates were evaluated by their ability to kill each other. The results, although of insufficient taxonomic value for a reliable separation of either species or genera, attest to the genomic heterogeneity for the killer character in the genus Pichia as well as the presumptive dual killer/sensitive identity for each single isolate. PMID- 1907821 TI - Net ultrafiltration may not eliminate backfiltration during hemodialysis with highly permeable membranes. AB - Backfiltration of dialysis solution can occur during hemodialysis with highly permeable membranes. A method has recently been developed for determining backfiltration rates in vitro at low dialysate flow rates by measuring changes in the local dialysate concentration of a marker macromolecule via sampling ports added to the hemodialyzer housing. In the present study, the influence of net ultrafiltration on backfiltration rates was determined for five commercial dialyzers containing membranes with different water permeabilities. In vitro experiments were performed (n = 3) using freshly donated whole blood at blood flow rates of 200 and 340 ml/min and at a dialysate flow rate of 100 ml/min. At zero net ultrafiltration, backfiltration rates increased with increasing membrane water permeability and ranged from 0.9 to 6.9 ml/min. At a net ultrafiltration rate of 10 ml/min, backfiltration was eliminated for dialyzers containing membranes with water permeabilities of less than 30 ml/h/mm Hg but remained significant for dialyzers with higher membrane water permeabilities. Therefore, despite a significant net ultrafiltration rate, backfiltration may still occur during hemodialysis with highly permeable membranes. PMID- 1907822 TI - Modulation of corneal wound healing after excimer laser keratomileusis using topical mitomycin C and steroids. AB - A 193-nm excimer laser system was used to create deep stromal ablations in seven New Zealand white rabbits and shallow ablations in three. Eyes were randomized for treatment with topical mitomycin C, steroids, and erythromycin; topical steroids and erythromycin; or topical erythromycin only. All treatment regimens were instituted twice daily for 14 days. All eyes reepithelialized normally within 3 to 5 days. During 10 weeks of follow-up, all eyes developed moderate reticular subepithelial haze without significant differences among treatment groups. Results of light, fluorescence, and electron microscopic examination showed anterior stromal scarring and markedly reduced new subepithelial collagen formation in the group treated with mitomycin C, corticosteroids, and erythromycin. Focal abnormalities of Descemet's membrane and endothelial abnormalities were present in all treatment groups. Combination therapy with topical steroids, mitomycin C, and erythromycin to control the corneal wound healing response after refractive laser surgery appears promising and warrants further study. PMID- 1907823 TI - Viral hepatitis A to E. An update. AB - The authors' aim is to present a survey of the current understanding of viral hepatitis with emphasis on hepatitis B and C and the mechanisms of prevention. Abbreviations used in this article are shown in Table 1. An overview of viral hepatitis A to E is provided in Table 2. PMID- 1907825 TI - Pharmacology of the pyrroloimidazole, SK&F 105809--II. Antiinflammatory activity and inhibition of mediator production in vivo. AB - SK&F 105809 [2-(4-methylsulfinylphenyl)-3-(4-pyridyl)- 6,7-dihydro-[5H] pyrrolo[1,2,a] imidazole] demonstrated unique antiinflammatory activities in murine models that are resistant to selective cyclooxygenase (CO) inhibitors. Both edema and inflammatory cell infiltration induced by the topical application of arachidonic acid to the mouse ear were decreased by SK&F 105809 (ED50 values of 44 mg/kg, p.o.). Polymorphonuclear leukocyte (PMN) infiltration following the intraperitoneal injection of either monosodium urate crystal or carrageenan was inhibited with ED50 values of 64 and 72 mg/kg, p.o., respectively. These inflammatory responses were unaffected by the selective cyclooxygenase inhibitor naproxen. SK&F 105809 also inhibited leukotriene B4 (LTB4) and prostaglandin E2 production in vivo in arachidonic acid-induced inflammatory exudates (ED50 values of 41 and 15 mg/kg, p.o., respectively). The inhibition of LTB4 production preceded the inhibition of PMN infiltration. The impact of inhibition of both 5 lipoxygenase (5-LO) and CO was seen with platelet-activating factor-induced vascular permeability which was inhibited markedly by SK&F 105809. However, the 5 LO inhibitor, phenidone, only strongly inhibited when coadministered with the selective CO inhibitor, indomethacin. In spite of a short half-life (14-18 min) for both SK&F 105809 and the active metabolite SK&F 105561 [2-(4- methylthiophenyl)-3-(4-pyridyl)-6,7-dihydro-[5H]-pyrrolo[1,2-a] imidazole], the pharmacological activity lasted at least 1.5 hr. The biochemical evidence of inhibition of interleukin-1 (IL-1) production and 5-LO and CO activity, in vitro, by the metabolite (SK&F 105561) seen in the companion paper (Marshall PJ, Griswold DE, Breton J. Webb EF, Hillegass LM, Sarau HM, Newton J Jr, Lee JC, Bender PE and Hanna N, Pharmacology of the pyrroloimidazole, SK&F 105809--I. Inhibition of inflammatory cytokine production and of 5-lipoxygenase- and cyclooxygenase-mediated metabolism of arachidonic acid. Biochem Pharmacol 42: 813 824, 1991) and inhibition of the fluid and cellular phases of the inflammatory response, in vivo, by SK&F 105809 suggest that this compound possesses a unique profile of activity. PMID- 1907824 TI - Pharmacology of the pyrroloimidazole, SK&F 105809--I. Inhibition of inflammatory cytokine production and of 5-lipoxygenase- and cyclooxygenase-mediated metabolism of arachidonic acid. AB - SK&F 105809 [2-(4- methylsulfinylphenyl)-3-(4-pyridyl)-6,7-dihydro-[5H] pyrrolo[1,2- a] imidazole] was determined to be a prodrug for the sulfide metabolite SK&F 105561 [2-(4- methylthiophenyl)-3-(4-pyridyl)-6,7-dihydro-[5H] pyrrolo[1,2-a] imidazole] which inhibited interleukin-1 (IL-1) production in vitro and both 5-lipoxygenase (5-LO) and prostaglandin H (PGH) synthase activities in vitro and ex vivo. SK&F 105561 inhibited partially purified 5-LO with a half-maximal concentration (IC50) of 3 microM. This inhibition was reversible, independent of preincubation time, and dependent on the concentration of the substrate arachidonic acid. SK&F 105561 also inhibited purified PGH synthase with the potency dependent on the level of peroxidase activity. The IC50 was 100 microM in the absence of peroxidase activity, whereas an IC50 of 3 microM was observed in the presence of peroxidase activity. Using human monocytes, SK&F 105561 inhibited A23187-stimulated prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) production with IC50 values of 0.1 and 2 microM, respectively. In addition, IL-1 production by lipopolysaccharide-stimulated human monocytes was also inhibited (IC50 2 microM). Oral administration of SK&F 105809 to rats resulted in a dose-related generation of SK&F 105561 and in the inhibition of thromboxane B2 and LTB4 production ex vivo with a half-maximal dose (ED50) of 15 and 60 mg/kg, respectively. SK&F 105561 showed weak inhibitory activity on 12 lipoxygenase with an IC50 of greater than 200 microM. Neither SK&F 105561 nor SK&F 105809 inhibited the stimulated-turnover of arachidonic acid-containing phospholipids in human monocytes or the activity of cell-free phospholipases A2 and C. Moreover, neither SK&F 105561 nor SK&F 105809 antagonized the binding of LTB4 or leukotriene D4 to membrane receptors. From these results, SK&F 105561, the active principle of SK&F 105809, acts as an inhibitor of both inflammatory cytokine and eicosanoid production. PMID- 1907826 TI - [Pharmacokinetics and local availability of mitomycin. The influence of vasoconstriction and chemoembolization]. AB - The influence of the vasopressin-pro-drug glycylpressine (GP) and of a chemoembolisation with Spherex starch-particles (SP) on the availability of mitomycin (CAS 50-07-7, mitomycin C, MMC) was investigated in 30 patients with liver metastases, MMC administration was performed after blocking of the common hepatic artery by different concentrations of SP and after different time intervals of GP. The comparison of plasma-levels after bolus injection without GP and after administration of MMC after 2, 5 and 15 min of vasoconstriction and after chemoembolisation with 450 mg or 900 mg SP, respectively, showed a remarkable reduction in the systemic circulation of MMC in the blood vessel system at about 40% (GP) and 45% (SP). A statistically significant influence on the pharmacokinetics of MMC with regard to CO, Vd, T 1/2zp, AUC and Cl(tot) was found, but not in t1/2el, t1/2biol and Vl. Both methods cause a distinctly accelerated diffusion of MMC into the tissue of the tumor region by change of the hemodynamics, leading to lowered side-effects. Thus the clinical picture was improved by MMC. PMID- 1907827 TI - [Amalgam bonding. An important change in operative dentistry. 2]. PMID- 1907828 TI - A head immobilization system for radiation simulation, CT, MRI, and PET imaging. AB - An aquaplast mask/marker immobilization system for the routine radiation therapy treatment of head and neck disease is described. The system utilizes a commercially available thermoplastic mesh indexed and mounted to a rigid frame attached to the therapy couch. The apparatus is designed to permit CT, MRI, and PET diagnostic scans of the patient to be performed in the simulation and treatment position utilizing the same mask, thereby facilitating image correlation. Studies employing weekly simulation indicate that patient treatment position movement can be restricted to 3 mm over the course of treatment. This easily constructed system permits rapid mask formation to be performed on the treatment simulator, resulting in an immobilization device comparable to masks produced with vacuum-forming techniques. Details of construction, verification, and central axis CT, MRI, PET markers are offered. PMID- 1907829 TI - The use of an universal wedge for asymmetric fields. AB - Beam collimators on newer linear accelerators may be collimated asymmetric to the central axis. The asymmetric beam has a non-flat profile adjusted to yield fields whose half widths are not symmetric about the central axis. While some treatment planning systems modify their programs to mimic the nonuniformity, ideally it is preferred to have a flat profile under the open beam. We have developed a universal wedge that can be used to flatten the field for a variety of jaw sizes and positions and energies for the Varian 2100C. The wedge flattens the field to +/- 3% over 80% of the field. PMID- 1907830 TI - Electron beam effective source surface distances for a high energy linear accelerator. AB - The design of the Varian Clinac 1800 linear accelerator electron applicator system does not allow clearance for all head and neck patients to be treated at the standard calibration distance of 100 cm. Discrepancies have been found between dose calculations using the inverse square law for extended distances and their measured data. A 4 X 4 cm2 applicator at an energy of 9 MeV, for example, had dose differences of 13 and 23% at distances of 105 and 110 cm SSD. Because of these discrepancies, effective source surface distances (SSDeff) were determined for all the standard electron energies and applicators of a Clinac 1800. These effective source surface distances ranged from 41.6 cm to 92.6 cm for the 4 X 4 cm2 cone/6 MeV electron beam through the 25 X 25 cm2 cone/20 MeV electron beam. A summary of these distances and an analysis of the clinical use of both a best fit SSDeff and a common SSDeff for patient dosimetry calculations is presented. PMID- 1907831 TI - Technical and therapeutic aspects of dynamic stereotactic radiosurgery. AB - A treatment procedure that results in a uniform dose in a single fraction over the entire treatment volume while minimizing the dose to other tissues has been developed to treat intracranial lesions such as arteriovenous malformations (AVMs). This technique is called dynamic stereotactic radiosurgery. Its main characteristic is simultaneous and continuous gantry and couch motion during the treatment procedure. It employs an isocentrically mounted linear accelerator as the source of radiation. Target localization is determined by digital subtraction angiography and CT. From results obtained in other centres, this technique has shown that an AVM less than 2.5 cm in diameter has an 85% chance of being completely obliterated within two years after a single treatment of stereotactic radiosurgery. This technique is suitable for those patients with inoperable, surgically inaccessible lesions, or whose current medical profile shows them to be high-risk candidates for surgical intervention. PMID- 1907832 TI - Antibiotic resistance among enterococci: current problems and management strategies. PMID- 1907833 TI - Using sodium chloride step gradients to fractionate DNA fragments. AB - A method is described for the separation of DNA fragments by ultracentrifugation through a sodium chloride step gradient. The gradients are quickly and easily prepared and require a five- to six-hour centrifugation. Fractionated samples of DNA may be directly examined by agarose gel electrophoresis, then further analyzed by Southern transfer and hybridization. A simple ethanol precipitation followed by several ethanol washes yields fragments that ligate efficiently to vector DNA. The method has been applied to separate chromosomal DNA restriction fragments as well as bacteriophage lambda arms from insert DNA. PMID- 1907834 TI - Evaluation of a follow-up system in a county health department's immunization clinic. AB - We designed a pilot follow-up system using two mailed reminders and evaluated it for use in the immunization clinic of a relatively large county health department in Washington State. Compliance with the recommended interval for DTP immunizations increased by 33.9% in the group of children receiving two postcard reminders compared to the control group. Over half of the respondents (52%) in the control group and 28% in the intervention group reported that transportation barriers and clinic problems prevented their return. PMID- 1907835 TI - [A neuroanatomical study of the vestibular efferent system, III: the origin and pathway of the axons]. AB - We have studied the vestibular efferent fibers pathway, after scratching the peripheral vestibular receptors and horseradish peroxidase injection, and TMB or DAB processing. We have proved the existence of a differentiated bundle in the main vestibular pathway, this bundle crosses the areas where the efferent somas have been situated, some of this fibers have been seen crossing the midline. It has not been possible to connect the efferent somas with the fibers. PMID- 1907836 TI - Overnight studies in severe chronic left heart failure: arrhythmias and oxygen desaturation. AB - Overnight studies were performed in 10 patients with severe chronic left heart failure (New York Heart Association grades III and IV) without pulmonary disease and in eight controls. Transcutaneous oxygen (Po2) and carbon dioxide tensions (Pco2) and oxygen saturation were measured and the electro-cardiogram was recorded. During sleep mean oxygen saturation fell to 92.7% (minimum 86.1%) from 95.1% when awake. During the night oxygen saturation was below 95% for 62% of the time, below 90% for 6% of the time, and below 85% for 1% of the time. In four patients there were oxygen desaturation dips (a fall of greater than 4% in oxygen saturation from a stable baseline that lasted greater than 30 s) with concurrent increases in Pco2. Two patients had bradycardia during the dips: in one there was non-sustained ventricular tachycardia during the dips and in the other there was ST depression (greater than 0.1 mV at 80 ms after the J point) during a dip. In the controls the fall in mean oxygen saturation from 95.4% when they were awake to 94.4% when they were asleep was less than the fall in patients with heart failure and there were no desaturation dips or arrhythmias. Thus patients with severe heart failure had episodes of oxygen desaturation during sleep, some of which were associated with arrhythmia. Such episodes may be related to the increased risk of sudden death in chronic heart failure. PMID- 1907837 TI - Syndrome X and hyperventilation. AB - The cardiorespiratory responses to exercise and forced hyperventilation were measured in 17 unselected patients with syndrome X (angina, positive exercise test, normal coronary arteriogram, no other cardiovascular disease) and compared with those in 15 healthy subjects. Forced hyperventilation produced hypocapnia and metabolic alkalosis but no chest pain or electrocardiographic change. Patients with syndrome X showed reduced maximum oxygen consumption with an increased respiratory exchange ratio at peak exercise, confirming that exercise was limited by skeletal muscle perfusion--and thus that the increase in cardiac output with exercise is limited in syndrome X as in heart failure. Arterial carbon dioxide tension (PCO2) homoeostasis during exercise was normal but the ventilatory cost of carbon dioxide excretion was increased in syndrome X (as in heart failure). End tidal PCO2 measurements correlated only poorly with arterial PCO2 in individual patients with syndrome X, providing a possible explanation for previous reports, based on end tidal PCO2 of inappropriate hyperventilation. Patients with syndrome X did not show inappropriate hyperventilation but they did show hyperventilation that was appropriate to maintain normal arterial PCO2 in the face of reduced cardiac reserve. PMID- 1907838 TI - Interindividual variability in the glucuronidation and sulphation of ethinyloestradiol in human liver. AB - 1. Glucuronidation and sulphation of ethinyloestradiol (EE2) was studied in human liver. Microsomal glucuronyltransferase activity was measured in 110 livers whose donors were 71 women and 39 men. Enzyme activity ranged between 12.6 and 242 pmol min-1 mg-1 protein, i.e. over a 19-fold range and the mean (+/- s.d.) glucuronyltransferase activity was 96.8 +/- 47.9 pmol min-1 mg-1 protein. 2. Cytosolic sulphotransferase activity was measured in 138 livers whose donors were 90 women and 48 men. Enzyme activity ranged between 14.4 and 98.2 pmol min-1 mg-1 protein, i.e. over a 7-fold range, and the mean (+/- s.d.) sulphotransferase activity was 43.7 +/- 18.6 pmol min-1 mg-1 protein. 3. Human liver glucuronyltransferase and sulphotransferase activities showed a unimodal distribution pattern. Enzyme activities were neither sex-related nor age dependent. Sulphotransferase activity did not correlate with glucuronyltransferase activity (n = 80) suggesting that the two enzymes are independently regulated. The ratio of specific glucuronyltransferase to sulphotransferase activity ranged between 0.15 and 8.0 (mean +/- s.d., 2.44 +/- 1.51) and was unimodally distributed. PMID- 1907840 TI - Lithium does not alter the renal response to a pressor dose of tyramine in man. AB - Renal clearance of lithium has been used as a marker of proximal tubular function in man. Recently, lithium pre-treatment has been shown to interfere with the natriuretic actions of some natriuretic agents in man. We have therefore investigated the effects of oral lithium carbonate (500 mg) on the natriuretic response to a pressor dose of tyramine (15 micrograms kg-1 min-1) in six normal volunteers. Lithium had no effect on baseline sodium excretion, nor did it affect the tyramine-induced increase in blood pressure and subsequent natriuresis. These results show that oral lithium carbonate (500 mg) does not appear to interfere with the pressure natriuretic response to tyramine in man. PMID- 1907839 TI - Pharmacokinetic interaction between propranolol and the HMG-CoA reductase inhibitors pravastatin and lovastatin. AB - 1. Single oral 20 mg doses of the HMG-CoA reductase inhibitors pravastatin and lovastatin, with and without concomitant propranolol (40 mg twice daily), were administered to 16 healthy male subjects participating in a randomized, four-way crossover study. 2. Serum concentrations of total and active inhibitors were measured by bioassay and concentrations of pravastatin, two pravastatin metabolites and lovastatin acid were measured by gas chromatography/mass spectrometry. 3. Coadministration of propranolol with pravastatin reduced the mean area under the serum concentration-time curve (AUC) of total inhibitors by 23%, of active inhibitors by 20% and of pravastatin by 16%. 4. Coadministration of propranolol with lovastatin also resulted in decreases in the mean serum AUC of total inhibitors by 18%, of active inhibitors by 12% and of lovastatin acid by 13%. 5. These decreases in systemic drug concentrations may reflect enhanced drug first-pass hepatic clearance in the presence of propranolol. 6. The clinical significance of these changes is likely to be small. PMID- 1907842 TI - [Diverticulosis of the small intestine. Observations on a complicated case]. AB - Small bowel diverticula, particularly the jejunal ones, are a rare disease with a poor and vague symptomatology. Sometimes detected by change under X-ray examinations or at surgery, they do not need any surgical treatment: only clinical and X-ray controls are required. Prophylactic resection of symptomatic low jejunal diverticula is controversial: patient's age and status will affect the indication to surgical treatment. Jejunal diverticulosis may generate serious, though not dramatic, symptoms: intestinal obstruction, inflammatory complications, haemorrhage, perforation of the diverticula are the most frequent emergencies which require an immediate surgical procedure. A clinical case is here reported. PMID- 1907841 TI - Ponalrestat does not cause a protein binding interaction with warfarin in diabetic patients. AB - Ponalrestat (Statil, ICI; Prodiax, Merck Sharp and Dohme) is an aldose reductase inhibitor which is highly protein bound. Ponalrestat markedly displaced warfarin from its protein binding in vitro at a concentration of 500 micrograms ml-1, but not at a concentration of 50 or 100 micrograms ml-1. Twelve diabetic patients (six males), age range 38-65 years, in receipt of chronic stable warfarin therapy, were given ponalrestat (600 mg daily) for 2 weeks in an open trial. A matching placebo tablet was administered for 1 week before and after the active treatment period. Patients were seen ten times (four times during the ponalrestat phase), and during the ponalrestat phase, plasma samples were also taken before and at 3 h after the daily dose of ponalrestat. At none of the visits was there any significant change in prothrombin ratio (INR), plasma total or unbound warfarin concentrations, or percentage protein binding of warfarin. No clinical complications of combination treatment were detected. The maximum ponalrestat concentration observed in the patients was approximately 100 micrograms ml-1. We conclude that no significant interaction between these drugs occurs at the doses of ponalrestat studied. PMID- 1907843 TI - Long term follow-up of patients with advanced prostatic cancer treated with nasal buserelin. AB - Sixty one men, with advanced prostatic cancer, were entered on a trial using a nasally administered gonadotropin-releasing hormone analogue agonist, buserelin, as first line treatment. This is the first trial to use intranasal buserelin without primary injections and without antiandrogens. No 'flare' phenomenon was observed. The only side effects were hot flashes (69%) and decreased libido (25%). The response rate of 82%, with a median response duration of 16 months, compares favourably to responses reported with orchidectomy or estrogens. Serum testosterone, FSH and LH were monitored at regular intervals. Mean serum testosterone baseline values of 15 nmol/L decreased to castrate levels, and remained low while patients were on study. It is concluded that intranasal buserelin is an effective, simple and safe method to achieve androgen deprivation and is an alternative to orchidectomy in the treatment of advanced prostatic cancer. PMID- 1907844 TI - 1H and 15N resonance assignments of oxidized flavodoxin from Anacystis nidulans with 3D NMR. AB - Proton and nitrogen-15 sequence-specific nuclear magnetic resonance assignments have been determined for recombinant oxidized flavodoxin from Anacystis nidulans (169 residues, Mr 19,048). Assignments were obtained by using 15N-1H heteronuclear three-dimensional (3D) NMR spectroscopy on a uniformly nitrogen-15 enriched sample of the protein, pH 6.6, at 30 degrees C. For 165 residues, the backbone and a large fraction of the side-chain proton resonances have been assigned. Medium- and long-range NOE's have been used to characterize the secondary structure. In solution, flavodoxin consists of a five-stranded parallel beta sheet involving residues 3-9, 31-37, 49-56, 81-89, 114-117, and 141-144. Medium-range NOE's indicate the presence of several helices. Several 15N and 1H resonances of the flavin mononucleotide (FMN) prosthetic group have been assigned. The FMN-binding site has been investigated by using polypeptide-FMN NOE's. PMID- 1907845 TI - Conformation and disulfide bond formation of the constant fragment of an immunoglobulin light chain: effect of truncation at the C-terminal region. AB - Constant fragments with different carboxyl terminals, CL(109-211), CL(109-207), and CL-(109-200), were prepared by limited carboxypeptidase P or Y proteolysis of the constant fragment, CL-(109-214), of a type lambda immunoglobulin light chain, and their conformations and stabilities, and formation of the disulfide bond from the reduced fragments, were studied. No change in conformation or stability was observed on removal of three residues from the C-terminal end. Removal of seven or more residues from the C-terminal end destabilized the CL fragment. The rate of disulfide bond formation from reduced CL(109-207) was about 7 times faster than that for CL(109-214). These findings suggest that elongation of the polypeptide chain at least beyond the 207th residue is necessary for folding of the CL fragment into a definite conformation. PMID- 1907846 TI - A water-mediated salt link in the catalytic site of Escherichia coli alkaline phosphatase may influence activity. AB - Escherichia coli alkaline phosphatase catalyzes the hydrolysis of a wide variety of phosphomonoesters at similar rates, and the reaction proceeds through a phosphoenzyme intermediate. The active site region is highly conserved between the E. coli and mammalian alkaline phosphatases. The three-dimensional structure of the E. coli enzyme indicates that Lys-328, which is replaced by histidine in all mammalian alkaline phosphatases, is bridged to the phosphate through a water molecule. This water molecule is also hydrogen bonded to Asp-327, a bidendate ligand of the one of the two zinc atoms. Here we report the use of site-specific mutagenesis to convert Lys-328 to both histidine and alanine. Steady-state kinetic studies above pH 7.0 indicate that both mutant enzymes have altered pH versus activity profiles compared to the profile for the wild-type enzyme. At pH 10.3, in the presence of Tris, the Lys-328----Ala enzyme is approximately 14-fold more active than the wild-type enzyme. At the same pH in the absence of Tris the Lys-328----Ala enzyme is still 6-fold more active than the wild-type enzyme. Both mutant enzymes have lower phosphate affinities than the wild-type enzyme at all pH values investigated. Pre-steady-state kinetics at pH 5.5 reveal that the Lys 328----Ala enzyme behaves very similar to the phosphate-free wild-type enzyme.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1907847 TI - A mammalian tryptophanyl-tRNA synthetase shows little homology to prokaryotic synthetases but near identity with mammalian peptide chain release factor. AB - Determination of the amino acid sequence of beef pancreas tryptophanyl-tRNA synthetase was undertaken through both cDNA and direct peptide sequencing. A full length cDNA clone containing a 475 amino acid open reading frame was obtained. The molecular mass of the corresponding peptide chain, 53,728 Da, was in agreement with that of beef tryptophanyl-tRNA synthetase, as determined by physicochemical methods (54 kDa). Expression of this clone in Escherichia coli led to tryptophanyl-tRNA synthetase activity in cell extracts. The open reading frame included two sequences analogous to the consensus sequences, HIGH and KMSKS, found in class I aminoacyl-tRNA synthetases. The homology with prokaryotic and yeast mitochondrial tryptophanyl-tRNA synthetases was low and was limited to the regions of the consensus sequences. However, a 90% homology was observed with the recently described rabbit peptide chain release factor (eRF) [Lee et al. (1990) Proc. Natl. Acad. Sci. 87, 3508-3512]. Such a strong homology may reveal a new group of genes deriving from a common ancestor, the products of which could be involved in tRNA aminoacylation (tryptophanyl-tRNA synthetase) or translation termination (eRF). PMID- 1907848 TI - Calcium retards NH2OH inhibition of O2 evolution activity by stabilization of Mn2+ binding to photosystem II. AB - Calcium is required for oxidation of water to molecular oxygen by photosystem II; the Ca2+ demand of the reaction increases upon removal of 23- and 17-kDa extrinsic polypeptides from detergent-derived preparations of the photosystem. Employing the manganese reductant NH2OH as a probe to examine the function of Ca2+ in photosystem II reveals that (1) Ca2+ slows the rate of NH2OH inhibition of O2 evolution activity, but only in photosystem II membranes depleted of extrinsic proteins, (2) other divalent cations (Sr2+, Cd2+) that compete for the Ca2+ site also slow NH2OH inhibition, (3) Ca2+ is noncompetitive with respect to NH2OH, (4) in order to slow inhibition, Ca2+ must be present prior to the initiation of NH2OH reduction of manganese, and (5) Ca2+ appears not to interfere with NH2OH reduction of manganese. We conclude that the ability of Ca2+ to slow the rate of NH2OH inhibition arises from the site in photosystem II where Ca2+ normally stimulates O2 evolution and that the mechanism of this phenomenon arises from the ability of Ca2+ or certain surrogate metals to stabilize the ligation environment of the manganese complex. PMID- 1907850 TI - Conversion of arginine to lysine at position 70 of human dihydrofolate reductase: generation of a methotrexate-insensitive mutant enzyme. AB - Arginine-70 of human dihydrofolate reductase (hDHFR) is a highly conserved residue which X-ray crystallographic data have shown to interact with the alpha carboxylate of the terminal L-glutamate moiety of either folic acid or methotrexate (MTX). The rationale for this study was to introduce a conservative amino acid residue change at position 70 (Arg----Lys) which might function as a titratable group and, thus, reveal possible quantitative changes in ligand binding and kinetic parameters as a function of pH. Such a mutant enzyme (R70K) has been constructed and expressed by using site-directed mutagenesis techniques. This substitution has a dramatic effect on the binding of MTX, which displays a 22,600-fold increase in the dissociation constant (KD) at pH 7.5 compared to that of the reported wild-type enzyme value. At this pH, the KD value for dihydrofolate (FAH2) for the R70K enzyme shows only a 7-fold increase over that for the wild-type hDHFR. The pH profiles of the Michaelis and dissociation constants for FAH2 and KD values for MTX for the mutant enzyme all show a 7-8 fold increase from pH 7.5 to 8.5 as compared to its wild-type counterpart. The binding of NADPH or the nonclassical inhibitor trimetrexate (TMQ) to either the wild-type or the mutant enzyme does not show such pH-dependent characteristics. Thus, since FAH2 and MTX interact with the guanidinium side chain of arginine-70 in the wild-type hDHFR, the replacement of this residue with a lysine in the R70K mutant appears to have resulted in the introduction of a titratable group with a perturbed pKa value of ca. 8.3.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1907849 TI - Regulation of c-jun gene expression in HL-60 leukemia cells by 1-beta-D arabinofuranosylcytosine. Potential involvement of a protein kinase C dependent mechanism. AB - 1-beta-D-Arabinofuranosylcytosine (ara-C) is an effective chemotherapeutic agent that incorporates into DNA and results in DNA fragmentation. Recent work has demonstrated that ara-C transiently induces expression of the c-jun immediate early response gene. The present studies in HL-60 myeloid leukemia cells extend these findings by demonstrating that the increase in c-jun mRNA levels at 6 h of ara-C treatment is regulated by a transcriptional mechanism. In contrast, the subsequent down-regulation of c-jun expression is controlled by a posttranscriptional decrease in the stability of the c-jun transcripts. Previous work in phorbol ester treated cells has indicated that c-jun expression is regulated by the activation of protein kinase C. The present results demonstrate that protein kinase C activity is increased in ara-C-treated cells. This increase was maximal at 60 min and remained detectable through 6 h of ara-C exposure. Moreover, the induction of c-jun transcripts by ara-C was inhibited by the isoquinolinesulfonamide derivative H7, but not by HA1004, suggesting that this effect is mediated by protein kinase C. Ara-C-induced c-jun expression was also inhibited by staurosporine, another inhibitor of protein kinase C. Taken together, these results indicate that the cellular response to ara-C includes the activation of protein kinase C and that ara-C potentially induces c-jun transcription by a protein kinase C dependent signaling mechanism. PMID- 1907851 TI - Inactivation mechanism of tetrameric beta-galactosidase by gamma-rays involves both fragmentation and temperature-dependent denaturation of protomers. AB - The radiation inactivation method is widely used to estimate the molecular size of membrane-bound enzymes, receptors, and transport systems in situ. The method is based on the principle that exposure of frozen solutions or lyophilized protein preparations to increasing doses of ionizing radiations results in a first-order decay of biological activity proportional to radiation inactivation size of the protein. This parameter is believed to reflect the "functional unit" of the protein defined as the minimal assembly of structure (protomers) required for expression of a given biological activity. We tested the functional unit as a concept to interpret radiation inactivation data of proteins with Escherichia coli beta-galactosidase, where the protomers are active only when associated in a tetramer. Gamma-Irradiation of beta-galactosidase at both -78 and 38 degrees C followed by quantitation of the residual unfragmented promoter band by SDS polyacrylamide gel electrophoresis yielded the protomer size, indicating that only one protomer is fragmented by each radiation hit. By following the enzyme activity as a function of dose it was found that only the protomer that has been directly hit and fragmented at -78 degrees C was effectively inactivated. In contrast, at 38 degrees C, it was the whole tetramer that was inactivated. beta Galactosidase cannot have two different functional units depending on temperature. The inactivation of the whole beta-galactosidase tetramer at 38 degrees C is in fact related to protomer fragmentation but also to the production of stable denatured protomers (detected by gel-filtration HPLC and differential UV spectroscopy) due to energy transfer from fragmented protomers toward unhit protomers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1907852 TI - Oxygen equilibrium properties of highly purified human adult hemoglobin cross linked between 82 beta 1 and 82 beta 2 lysyl residues by bis(3,5-dibromosalicyl) fumarate. AB - We investigated oxygen equilibrium properties of highly purified human adult hemoglobin cross-linked between lysine-82 beta 1 and lysine-82 beta 2 by a fumaryl group, which is prepared by reaction of the CO form with bis(3,5 dibromosalicyl) fumarate. The cross-linked hemoglobin preparation isolated by the previous purification method, namely, gel filtration in the presence of 1 M MgCl2 followed by ion-exchange chromatography, was found to be contaminated with about 20% of an electrophoretically silent impurity that shows remarkably high affinity for oxygen. This impurity was separated from the desired cross-linked hemoglobin by a newly developed purification method, which utilizes a difference between the authentic hemoglobin and the impurity in reactivity of the sulfhydryl groups of cysteine-93 beta toward N-ethylmaleimide under a deoxygenated condition. After this purification procedure, the oxygen equilibrium properties of purified cross linked hemoglobin in the absence of organic phosphate became very similar to those of unmodified hemoglobin with respect to oxygen affinity, cooperativity, and the alkaline Bohr effect. The functional similarity between the cross-linked hemoglobin and unmodified hemoglobin allows us to utilize this cross-linking for preparing asymmetric hybrid hemoglobin tetramers, which are particularly useful as intermediately liganded models. Previous studies on this type of cross-linked hemoglobin should be subject to reexamination due to the considerable amount of the impurity. PMID- 1907854 TI - Reengineering the catalytic lysine of aspartate aminotransferase by chemical elaboration of a genetically introduced cysteine. AB - The active-site essential catalytic residue of aspartate aminotransferase, Lys 258, has been converted to Cys (K258C) by site-directed mutagenesis. This mutant retains less than 10(-6) of the wild-type activity with L-aspartate. The deleted general base was functionally replaced by selective (with respect to the other five cysteines in wild type) aminoethylation of the introduced Cys 258 with (2 bromoethyl)amine following reversible protection of the nontarget sulfhydryl groups at different stages of unfolding. The chemically elaborated mutant (K258C EA) is 10(5) times more reactive than is K258C and has a kcat value of approximately 7% of that of wild type (WT). Km and KI values are similar to those for WT. The acidic pKa controlling V/KAsp is shifted from 7.3 (WT) to 6.0 (mutant). V/K values for amino acids are approximately 3% of those found for WT, whereas they are approximately 20% for keto acids. The value of DV increases from 1.6 for WT to 3.4 for the mutant, indicating that C alpha proton abstraction constitutes a more significant kinetic barrier for the latter enzyme. A smaller, but still significant, increase in D(V/KAsp) from 1.9 in WT to 3.0 in the mutant shows that the forward and reverse commitment factors are inverted by the mutation. The acidic limb of the V/KAsp versus pH profile, is lowered by 1.3 pH units, probably reflecting the similar difference in the basicity of the epsilon NH2 group in gamma-thialysine versus that in lysine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1907853 TI - Intramolecular semiquinone disproportionation in DNA. Pulse radiolysis study of the one-electron reduction of daunorubicin intercalated in DNA. AB - The one-electron reduction of daunorubicin, a quinonic antitumor antibiotic, intercalated in DNA was studied by pulse radiolysis using carboxyl radicals as reductants. The reaction's first stage is the daunorubicin semiquinone formation (k = 1.9 x 10(8) mol-1.dm3.s-1) in a way entirely consistent with a simple competition between .COO- disproportionation and the drug reduction. The semiquinone drug disappears by a first-order reaction (k = 1340 s-1) producing the hydroquinone form. This reaction leads to an equilibrium similar to the one without DNA and the equilibrium constant is very close to its value free in water (Kc approximately 25). In addition, the stoichiometry of the first-order reaction is the one of a dismutation process. Therefore, it appears that the disproportionation occurs along an intramolecular path across DNA. This migration takes place under our experimental conditions, over a distance of ca. 100 base pairs, with a mobility of ca. 4.4 X 10(-11) m2.V-1.s-1, similar in magnitude to an excess electron mobility in doped organic polymers. PMID- 1907855 TI - Hepatobiliary delivery of polyaminopolycarboxylate chelates: synthesis and characterization of a cholic acid conjugate of EDTA and biodistribution and imaging studies with its indium-111 chelate. AB - A conjugate in which the steroid nucleus of cholic acid was linked to EDTA via an 11-atom spacer was obtained by reacting the succinimidyl ester of cholic acid with the amine formed by reaction of a benzyl isothiocyanate derivative of EDTA with N-(tert-butoxycarbonyl)ethylenediamine and subsequent deprotection. Potentiometric titration studies with model complexes showed that the EDTA moiety retained the ability to form 1:1 chelates of high thermodynamic stability, although formation constants were some 3-4 log K units lower for complexes of the conjugate than for the analogous chelates with underivatized EDTA. A complex formed between the cholic acid-EDTA conjugate and 111InIII was clearly rapidly into the liver when injected iv into mice, with subsequent excretion from the liver into the gastrointestinal tract being complete within 1 h of injection. Radioscintigraphic imaging studies conducted in a rabbit given the 111In-labeled conjugate also showed early liver uptake followed by rapid clearance from the liver into the intestine, with good visualization of the gallbladder in images obtained at 20-25 min postinjection. It is concluded that conjugation to cholic acid provides a useful means for the hepatobiliary delivery of EDTA chelates that otherwise exhibit predominantly extracellular distribution and renal clearance. PMID- 1907856 TI - Multicentre evaluation of the blood gas-electrolyte-analyser "BGE". AB - A multicentre evaluation of the blood gas-electrolyte-haematocrit-analyser BGE (Fa. Instrumentation Laboratory), following as far as possible the ECCLS guidelines for multicentre evaluation of blood gas analysers, was performed by three laboratories. The rules of the evaluation protocol were extended to the electrolyte and haematocrit determinations. The BGE proved to be easy to operate and maintain. The stability of the measuring system was good. The within-run imprecision of all electrodes was excellent. The same applies to the between-day imprecision, except for the calcium measurements. The systematic deviation of the gas electrodes was very small. Comparison studies revealed clinically significant deviations only for ionized calcium. Some suggestions for further improvements are made. PMID- 1907857 TI - Time-dependent changes in gonadotropin synthesis following gonadectomy in the frog, Rana pipiens. AB - Anterior pituitary glands from frogs gonadectomized (gonadx) for various periods (0-90 days) were labeled in vitro with 35S-methionine. Shortly (7-10 days) after gonadx, plasma levels and the in vitro basal pituitary secretion of LH and FSH are elevated compared to values in sham-operated frogs. However, LH and FSH become dissociated in long-term (over 40 days) gonadx frogs; FSH remains elevated while LH returns to sham levels. Gth (gonadotropin: LH and FSH) synthesis shows a similar pattern. Gth synthesis becomes elevated after gonadx, but returns to sham levels after 80 days. In short-term (15 days) gonadx females, LH and FSH each comprise approximately the same percentage of counts immunoprecipitated. In contrast, in long-term (90 days) gonadx females, nearly 100% of Gth synthesis can be accounted for solely by FSH; LH synthesis is barely or not detectable. Although the elevated in vitro secretion rate of LH and FSH following gonadx diminishes within 24 h in culture, Gth synthesis remains elevated. This study demonstrates that although the pattern of Gth secretion and synthesis generally parallel each other following gonadx, these two cellular processes can be dissociated from one another. Furthermore, it appears that in frogs, not only the secretion, but also the synthesis, of LH and FSH may be under independent regulation. PMID- 1907858 TI - Bicarbonate: carbon-dioxide regulation of sperm capacitation, hyperactivated motility, and acrosome reactions. AB - The bicarbonate: CO2 (HCO3-:CO2) concentration dependencies of hamster sperm motility, spontaneous acrosome reactions, and zona penetration (used to assay the zona-induced acrosome reaction) were examined. A cross-over experimental design was used to segregate effects on early stages of capacitation, spanning the first 5 h of incubation, from those on acrosome reactions and zona penetration during the last 1 h. After 5 h, HCO3-:CO2 concentrations were increased, decreased, or kept the same for 1 h. Compared to no HCO3-:CO2, as little as 2.9 mM: 0.6% HCO3 :CO2 increased the sperm motility index (MI) by 2.7-3.6 times. When HCO3-:CO2 was continuously present, both progressive and hyperactivated motility were stimulated by HCO3-:CO2 in a dose-dependent manner by 3-4 h, well before completion of capacitation. Stimulation of acrosome reactions or zona penetration, by addition of HCO3-:CO2 to sperm for 1 h late in capacitation, depended mainly on levels of HCO3-:CO2 present earlier in capacitation. When 25 mM: 5% HCO3-:CO2 was added only at 5 h, responses were significantly lower than with sperm treated continuously with the same concentration of HCO3-:CO2, being 2.5 times lower for MI, 2 times lower for acrosome reactions, and 6.3 times lower for zona penetration. In contrast, decreasing HCO3-:CO2 to suboptimal levels after 5 h did not decrease any 6-h sperm responses significantly. The average maximal and one-half maximal preincubation HCO3- concentrations for all responses were 34.2 +/- 1.0 and 9.2 +/- 0.3 mM, respectively. Zona penetration and hyperactivation were highly correlated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1907859 TI - Seasonal changes in plasma concentrations of immunoreactive inhibin and testicular activity in male Japanese monkeys. AB - Seasonal changes in plasma immunoreactive (ir-) inhibin, testosterone, LH, and FSH concentrations were examined in five sexually mature male Japanese monkeys (Macaca fuscata fuscata) housed indoors individually, to explore the reproductive cyclicity in the male. Blood samples were collected monthly throughout one year, and testicular size, semen volume, and number of sperm in the semen were ascertained at the same time in the same animals. Semen samples were obtained by penile electrostimulation. The results showed a clear seasonal increase in all parameters: plasma ir-inhibin, testosterone, testicular size, semen volume, and total number of sperm in the liquid portion of the semen during the autumn and winter months in synchrony with the natural breeding season. In contrast, plasma LH and FSH remained unchanged throughout the year, although plasma FSH tended to increase during the breeding season concomitant with an increase in plasma ir inhibin. A significant positive correlation between FSH and ir-inhibin was observed in two of five monkeys. The positive correlations between plasma ir inhibin and testicular activities during both the developing and regressing phases of the testicular cycle indicate that plasma ir-inhibin is a useful indicator of testicular activity as well as an indicator of Sertoli cell function in the Japanese monkey. PMID- 1907860 TI - Zebra chorionic gonadotropin: partial purification and characterization. AB - Six samples of pregnant zebra (z) serum from the first and second trimesters of pregnancy were analyzed by RIA and shown to have chorionic gonadotropin levels comparable to that of the mare (0.9-5.3 micrograms/ml); first trimester levels in most cases were higher than second trimester levels. A pool of the sera (10 ml) was fractionated by methods previously employed for the purification of equine (e) and donkey (d) chorionic gonadotropin to achieve a concentration of the zebra chorionic gonadotropin (zCG). A yield of 1.0 mg of glycoprotein was obtained. HPLC analysis of the material indicated the content of zCG to be about 7%. Its molecular size as judged by Ve/Vo values is smaller than eCG, greater than ovine LH, and about the same as equine LH. The zCG was tested in RIAs for LH and eCG, radioreceptor assays (RRA) for LH and FSH, and the rat testis Leydig cell assay for LH. Comparisons were made with equine and donkey chorionic gonadotropin, and equine and zebra LH. The results, preliminary because the preparation is not of high purity, showed that zCG is bioactive as an LH; immunologically similar to eCG, eLH, dCG, and zLH; and competes in RRAs for LH but not FSH receptors. It differs, therefore, from eCG and eLH--which have high levels of intrinsic FSH activity, and is more like dCG, dLH, and zLH--all of which have minimal if any FSH activity. PMID- 1907861 TI - The superovulation of synchronous adult rats using follicle-stimulating hormone delivered by continuous infusion. AB - The estrous cycles of adult female rats were synchronized with an LHRH agonist on the morning of Day -4 (Day 0 = day of mating). On Day -2, animals received s.c. implants of continuous-infusion osmotic minipumps containing different doses of an FSH preparation (Folltropin) in combination with hCG at various ratios of hCG:FSH or were given single injections of eCG in doses ranging from 15 IU to 60 IU. Rats infused with the optimal dose (3.4 U/day) of FSH ovulated 44.1 +/- 5.4 oocytes/rat while rats treated with the most effective dose (60 IU) of eCG ovulated only 20.5 +/- 4.3 oocytes/rat on the morning of Day 1. The inclusion of hCG in pumps at ratios from 0.188:1 to 0.75:1 (hCG:FSH) had no significant effect on ovulation rate. The importance of synchronization of estrus in successful superovulation was demonstrated by the finding that only 70% of the unsynchronized animals ovulated (29.1 +/- 4.8 oocytes/rat) whereas 95% of the synchronized animals ovulated (51.0 +/- 3.6 oocytes/rat). Oocyte viabilities were assessed by determining fertilization rates and embryonic development in vivo following mating with fertile males. In rats superovulated by use of the FSH regimen, 92% (39.0 +/- 4.1) of the recovered embryos were 1-cell zygotes on Day 1, 89% (36.3 +/- 5.6) were at the 2-cell embryo stage of development on Day 2, and 88% (28.8 +/- 2.2) were at the morula and blastocyst stages on Day 5 following mating on Day 0. The high ovulation rates and oocyte viability in rats receiving infusions of Folltropin following estrus synchronization offer a reliable method for superovulation of adult rats. PMID- 1907863 TI - In vitro effects of epidermal growth factor, insulin-like growth factor-I, fibroblast growth factor, and follicle-stimulating hormone on hamster follicular deoxyribonucleic acid synthesis and steroidogenesis. AB - Preantral (stages 1-6) and antral (stages 7-10) follicles from proestrous hamsters were exposed for 24 h to 1, 5, 10, 50, and 100 ng/ml of epidermal growth factor (EGF), insulin-like growth factor-I (IGF-I), and fibroblast growth factor (FGF) and 1 microCi [3H]thymidine to determine the rate of DNA replication. FSH (100 ng/ml) was used as a positive control. Synergism was also studied by using suboptimal doses of growth factors (1 ng/ml) and FSH (5 ng/ml). Optimal doses (50 ng/ml) of EGF, IGF-I, and FGF, and 100 ng/ml FSH significantly enhanced follicular DNA replication, whereas suboptimal doses of FSH, EGF, and IGF-I affected only a few preantral stages, and FGF was totally ineffective. FGF significantly inhibited DNA synthesis induced by a suboptimal dose of EGF but did not affect IGF-I-induced DNA replication. Paradoxically, a combination of suboptimal doses of all three growth factors significantly (p less than 0.05) stimulated DNA synthesis for all stages; FSH (5 ng/ml) had no additive effect. FSH significantly stimulated follicular progesterone (P4), androstenedione (A), and estradiol-17 beta (E2) accumulation, but significant P4 accumulation from stages 3-10 was observed only after optimal EGF exposure; A and E2 accumulations were unaffected by any of the growth factors. These results indicate that EGF, IGF-I, and FGF stimulate DNA replication to hamster preantral and antral follicles, and may play roles as intraovarian factors regulating folliculogenesis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1907862 TI - Plasma sex steroid-binding protein in mature heifers: effects of reproductive status, nutritional level, and porcine growth hormone, and estradiol-17 beta treatments. AB - In heifers, the specific 5 alpha-dihydrotestosterone (5 alpha-DHT) binding to sex steroid-binding protein (SBP) was 53 nM in midluteal phase and was 20% lower (p less than 0.05) in early luteal phase. In ovariectomized heifers on a high (H) or a low (L) energy diet, SBP bound testosterone with high specificity and estradiol 17 beta (E2) with a lower specificity; the affinity constant with 5 alpha-DHT was similar in the two groups independent of diet (Ka = 1.0 and 1.3 x 10(9) x M-1 for H and L heifers, respectively). Electrophoretic mobility of SBP was not affected by undernutrition. The specific 5 alpha-DHT binding to SBP in anestrous heifers compared to heifers in early luteal phase was 17% lower 18 days after cessation of ovarian activity (p less than 0.05) and 35% lower after 78 days of anestrus (p less than 0.001). Specific 5 alpha-DHT binding to SBP was 33% lower (p less than 0.001) in L heifers than in H heifers (40 nM). Porcine growth hormone (pGH) and E2 injections increased specific 5 alpha-DHT binding to SBP in both H and L heifers, but the effect depended on diet. Simultaneous injections of pGH and E2 increased specific binding in H heifers (p less than 0.02), whereas it had no effect in L heifers. We conclude that SBP binding capacity varies with ovarian activity in heifers and that nutritional status is one factor of regulation of SBP binding capacity because it affects binding and modifies the SBP response to stimulating factors such as pGH and E2. PMID- 1907864 TI - Cellular localization of ovarian prostaglandin endoperoxide synthase during pseudopregnancy in the rat. AB - The specific cellular localization of prostaglandin endoperoxide (PGH) synthase, the enzyme responsible for initiating the conversion of arachidonic acid to prostaglandins, was studied throughout pseudopregnancy in the rat. Pseudopregnancy was induced by administration of eCG (20 IU) to immature, 27-day old rats followed by hCG injection (10 IU) on Day 29. Animals were necropsied on Days 1 (Day 1 = 1 day post hCG), 5, 9, and 13 of pseudopregnancy. Ovaries were removed and processed for cellular identification of PGH synthase by immunohistochemistry. Immunoreactive PGH synthase was distributed throughout the CL at each of the 4 different days of pseudopregnancy, with the majority of the luteal cells exhibiting varying degrees of staining. The connective tissue centrum of the CL, however, lacked PGH synthase immunoreactivity. Quantitative assessment of the immunostaining distribution was accomplished with a computer based image analysis program (Kontron IBAS). Results are expressed as the percentage of a digitized luteal area that contained intense immunoreactivity between Day 1 (0.6 +/- 0.2% immunoreactive area) and Day 5 (16.8 +/- 2.7%) of pseudopregnancy. The area of luteal immunostaining was similar on Day 5 and Day 9 (16.8 +/- 2.7% and 14.7 +/- 2.0%, respectively) followed by a decrease (p less than 0.05) in immunoreactivity on Day 13 (9.1 +/- 2.2%). The region of the CL adjacent to the germinal epithelium had an increase (p less than 0.01) in PG synthase staining distribution compared to the region of the CL adjacent to the ovarian medulla on all days of pseudopregnancy except Day 1. These findings demonstrate that PGH synthase is present in the rat CL throughout pseudopregnancy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1907865 TI - Cell-attached patch clamp study of the electropermeabilization of amphibian cardiac cells. AB - Potential gradients imposed across cell or lipid membranes break down the insulating properties of these barriers if an intensity and time-dependent threshold is exceeded. Potential gradients of this magnitude may occur throughout the body, and in particular in cardiac tissue, during clinical defibrillation, ablation, and electrocution trauma. To study the dynamics of membrane electropermeabilization a cell-attached patch clamp technique was used to directly control the potential across membrane patches of single ventricular cells enzymatically isolated from frog (Rana pipiens) hearts. Ramp waveshapes were used to reveal rapid membrane conductance changes that may have otherwise been obscured using rectangular waveshapes. We observed a step increase (delta t less than 30 microseconds) or breakdown in membrane conductance at transmembrane potential thresholds of 0.6-1.1 V in response to 0.1-1.0 kV/s voltage ramps. Conductance kinetics on a sub-millisecond time scale indicate that breakdown is preceded by a period of instability during which the noise and amplitude of the membrane conductance begin to increase. In some cells membrane breakdown was observed to be fully reversible when using an intershock interval of 1 min (20-23 degrees C). These findings support energetic models of membrane electropermeabilization which describe the formation of membrane pores (or growth of existing pores) to a conducting state (instability), followed by a rapid expansion of these pores when the energy barrier for the formation of hydrophilic pores is overcome (breakdown). PMID- 1907867 TI - End-tidal CO2 monitoring for patients receiving epidural opiates. PMID- 1907866 TI - Gd3+ vibronic side band spectroscopy. New optical probe of Ca2+ binding sites applied to biological macromolecules. AB - A new spectroscopic technique is presented for obtaining infraredlike spectra of the binding sites of Ca2+ and other metals in biological macromolecules. The technique, based on the Ca(2+)-like binding properties of Gd3+, utilizes vibronic side bands (VSB) that appear in Gd3+ fluorescence. In the fluorescence spectrum of Gd3+, the separation in photon frequency between a VSB and its electronic origin at approximately 32,150 cm-1 (approximately 311 nm) is a direct measure of the vibrational frequency of a ligand coordinated to Gd3+ ion. As a consequence, the VSB are uncomplicated by molecular vibrations distant from the Gd3+ binding site. The vibrational spectra resulting from the VSB of Gd3+ coordinated to a Ca2+ binding protein, a phospholipid, and DNA are presented. PMID- 1907868 TI - IPPV plus low-flow intermittent oxygen insufflation (end-exhalation to beginning inhalation) does not improve CO2 elimination. AB - It has been previously reported that continuous insufflation of low-flow O2 (0.05 to 0.20 L/kg/min), both supracarinally and subcarinally, in addition to intermittent positive-pressure ventilation (IPPV) (IPPV + O2 at a specific flow rate) caused progressive hemodynamic deterioration in patients. As demonstrated in a subsequent mechanical lung model, the hemodynamic deterioration was most probably due to lung hyperexpansion. The purpose of this study was to test the hypothesis that the O2 retarded the outflow of gas from the lung during exhalation and that if the insufflation were limited to the period of time from the end of tidal exhalation (EE) to the beginning of the next IPPV tidal inspiration (BI), lung hyperexpansion would not occur. The use of intermittent O2 in addition to IPPV was studied in both a mechanical lung model and in patients under general anesthesia; the mechanical lung model permitted direct examination of lung volume, and the patient study allowed determination of gas exchange effects. In the mechanical lung model and in the patients, a wide range of EE-BI O2 flow rates were used; respectively, 1 to 40 L/min and 0.05 to 0.20 L/kg/min. In the mechanical lung model, lung pressure and volume at EE and end-inspiration did not increase as long as the O2 flow was kept at or below 10 L/min. In the patients, airway pressure and hemodynamics did not change appreciably, but there was also no increase in CO2 elimination.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1907869 TI - Partial conservation of the 5' ndhE-psaC-ndhD 3' gene arrangement of chloroplasts in the cyanobacterium Synechocystis sp. PCC 6803: implications for NDH-D function in cyanobacteria and chloroplasts. AB - The psaC gene, which encodes the 8.9 kDa iron-sulfur containing subunit of Photosystem I, has been sequenced from Synechocystis sp. PCC 6803 and shows greater similarity to reported plant sequences than other cyanobacterial psaC sequences. The deduced amino acid sequence of the protein encoded by the Synechocystis psaC gene is identical to the tobacco PSA-C sequence. In plants psaC is located in the small single-copy region of the chloroplast genome between two genes (designated ndhE and ndhD) with similarity to genes encoding subunits of the mitochondrial NADH Dehydrogenase Complex I. The 5' ndhE-psaC-ndhD3' gene arrangement of higher plants is only partially conserved in Synechocystis. An open reading frame (ORF) upstream of the Synechocystis psaC gene has 85% identity to the tobacco ndhE gene. Downstream of psaC there is a 273 bp ORF with 48% identity to the 5' portion of the tobacco ndhD gene (1527 bp). psaC, ndhE and the region of similarity to ndhD are present in a single copy in the Synechocystis genome. Part of the wheat ndhD gene was sequenced and used as a probe for the presence of the 3' portion of the ndhD gene. The wheat ndhD probe did not hybridize to Synechocystis or Anabaena sp. PCC 7120 genomic DNA, but did hybridize to Oenothera chloroplast DNA. These results indicate the complete ndhD gene is absent in two cyanobacteria, and raises the question of what role, if any, the ndhD gene product plays in the facultative heterotroph Synechocystis sp. PCC 6803. PMID- 1907870 TI - Two antiviral proteins, gp35 and gp22, correspond to beta-1,3-glucanase and an isoform of PR-5. PMID- 1907871 TI - Transgene expression variability (position effect) of CAT and GUS reporter genes driven by linked divergent T-DNA promoters. AB - Forty-five individually transformed clonal tobacco callus lines were simultaneously assayed for both chloramphenicol acetyltransferase (CAT) and beta glucuronidase (GUS) activity resulting from expression of introduced reporter genes driven by the adjacent and divergent mannopine (mas) promoters. Excluding lines in which one or both of the enzyme activities was essentially zero, the activities of the reporter genes varied by as much as a factor of 136 (CAT) and 175 (GUS) between individual transformants. Superimposed upon the high degree of inter-clonal expression variability was an intra-clonal variability of 3-4-fold. The observed degree of intra-clonal reporter gene activity may be more extreme because of the regulatory characteristics of the mannopine promoters, but must still be addressed when considering the limitations of reporter gene-based analysis of transgene function and structure. There was no consistent correlation between the expression levels of the introduced CAT and GUS genes since the ratio of GUS to CAT activities (nmol min-1 mg-1) within individual lines varied from 0.05 to 49. Even divergent transcription from two directly adjacent promoter regions (both contained within a 479 bp TR-DNA fragment) is insufficient to guarantee concurrent expression of two linked transgenes. Our quantitative data were compared to published data of transgene expression variability to examine the overall distribution of expression levels in individual transformants. The resulting frequency distribution indicates that most transformants express introduced transgenes at relatively low levels, suggesting that a potentially large number of Agrobacterium-mediated transformation events may result in silent transgenes. PMID- 1907873 TI - Membrane surface antigen expression on neutrophils: a reappraisal of the use of surface markers for neutrophil activation. AB - Neutrophil research relies largely on studies with highly purified cells. Yet the isolation procedures induce changes in surface expression of several proteins. We used a large panel of monoclonal antibodies (MoAbs) to characterize in detail the phenotypic changes during isolation and stimulation of human neutrophils. Centrifugation on density gradients appears to be the crucial step that causes an increase in expression of antigens not detectable on neutrophils in whole blood samples (cytochrome b558 recognized by MoAb 7D5; and CD10) or expressed at significantly lower levels (CD11a, CD11b, CD11c, CD13, CD16, CD45, and CD67). Other antigens were unaffected by the density gradient centrifugation step (CD32, CD54, CD58, Leu-8, HLA class I). Upregulation of antigens was also determined by stimulation of purified neutrophils. Upregulation of CD63 was an excellent marker for release from azurophil granules. We subsequently related the surface antigen expression to functional activities of purified neutrophils. From these experiments, we concluded that 7D5-as "early activation" marker--does not necessarily discriminate between primed or resting neutrophils with respect to NADPH oxidase activity. PMID- 1907872 TI - Post-transcriptional regulation by light of the biosynthesis of Euglena ribulose 1,5-bisphosphate carboxylase/oxygenase small subunit. AB - In Euglena gracilis, the amounts of the mature small subunit of ribulose-1,5 bisphosphate carboxylase/oxygenase (Rubisco) increase during cell greening, while an analysis of the transcripts, performed at different stages of chloroplast development, shows no difference in the amounts of the corresponding mRNA. Pulse chase experiments followed by immunoprecipitation show a significant increase in the rate of synthesis of the large molecular weight precursor (which consists of a transit peptide followed by eight small subunits) beginning after 12 h of illumination. Nevertheless, its half life does not change significantly during the chloroplast development. The results presented strongly suggest that the regulation of the expression of the Rubisco small subunit occurs at the translational level. PMID- 1907875 TI - Percutaneous endoscopic gastrostomy. AB - Percutaneous endoscopic gastrostomy is a useful alternative to long-term nasogastric feeding or surgical gastrostomy for dysphagic patients. It is simple to perform and is relatively safe. PMID- 1907874 TI - Successful allogeneic bone marrow transplantation in a 6.5-year-old male for severe aplastic anemia complicating orthotopic liver transplantation for fulminant non-A-non-B hepatitis. AB - We report the case of a 6.5-year-old male who received an unrelated orthotopic liver transplant for hepatic failure and encephalopathy following non-A-non-B hepatitis and subsequently developed severe aplastic anemia. For treatment of his aplastic anemia, he received a successful marrow transplant from his 9-year-old genotypically HLA-identical sister following conditioning with cyclophosphamide 200 mg/kg and anti-thymocyte globulin 90 mg/kg. Significant veno-occlusive disease of the liver and graft-versus-host disease did not occur. The patient remains alive without clinical chronic active hepatitis or need for blood product therapy. His hematocrit is 36%, white blood cell count 9.7 x 10(3)/mm3, and platelet count 1.7 x 10(5)/mm3 almost 2 years after marrow transplantation. PMID- 1907876 TI - Euthanasia of mink (Mustela vison) by means of carbon dioxide (CO2), carbon monoxide (CO) and nitrogen (N2). AB - The time periods and the behavioural pattern of mink euthanized with carbon dioxide (CO2), 100% and 70%, carbon monoxide (CO), 4%, and nitrogen (N2), 100%, are described. The time between the placement of the animal in a glass box and the first symptoms of incoordination (phase I), the period of loss of consciousness (phase II), and, finally, the coma phase until cessation of respiration (phase III) using three groups each of 10 pastel male mink each were recorded. Phase I times ranged from 14 s for CO2, 31 s for N2, and 49 s for CO. In phase II, the difference was even more pronounced, being 5 s for CO2, 15 s for CO, and 45 s for N2. In phase III, the time was 58 s for N2, 134 s and 151 s for CO2 and CO respectively. Hence, the critical period from the time when the animals were placed in the glass box till unconsciousness occurred (phase I and II) was 19 s for CO2, 64 s for CO, and 76 s for N2. The total course of euthanasia was 153 s for CO2, 215 s for CO, and 134 s for N2. The following minimum times will be required before it can be judged to be safe to remove the animals: CO2 and N2: 5 min, and for CO: 6.5 min. In a supplementary experiment, involving a mixture of 70% CO2 and 30% atmospheric air, it was not possible within the allotted time to kill adult male mink.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1907877 TI - A factor analysis of the human's corpus callosum. AB - We have recently developed a computer program for measuring midsagittal sections of the human corpus callosum, similar to one used for the rat. Callosal area, perimeter, axis length, and 99 widths for 104 subjects were entered into a factor analysis in order to define regional clusters. Seven width factors were obtained. Regional widths were found to be sensitive to Sex X Handedness interactions in the anterior body, with right-handed females and left-handed males being larger. In the posterior body males had wider callosa than females. A further analysis within the 'isthmus' region compared consistent and non-consistent right-handed males and females. Consistent right-handed males and both female groups had smaller callosa than non-consistent right-handed males. These findings confirmed the use of consistency of handedness as an important independent variable with respect to human callosal morphology. PMID- 1907878 TI - Magnetic resonance imaging of rat brain following in vivo disruption of the cerebral vasculature. AB - Intravenous administration of hyperosmotic mannitol into rats produced a disruption of the blood-brain barrier (BBB). This was visualized by T1 weighted magnetic resonance (MR) imaging following intravenous administration of the MR contrast agent gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA). Following administration of the Gd-DTPA there was an increase in signal intensity corresponding to the cerebral cortex. There was also an increase in signal intensity in features corresponding to the lateral ventricles. However, there was no increase in signal intensity within the striatum indicating that the vasculature within the striatum was resistant to disruption by the hyperosmotic mannitol. The tumors formed by C-6 glioma cells were isointense with rat brain on precontrast MR images. Following intravenous administration of Gd-DTPA, in a representative rat, the tumor was visualized as areas of high signal intensity. There was no enhancement of normal brain by Gd-DTPA. Thus, the tumor had different vascular properties than the host brain with respect to permeability of the contrast agent. Furthermore, Gd-DTPA did not enter the normal brain via the tumor. Thirty days following unilateral injection of kainic acid (KA: 5 nmol) into rat striatum, the shrinkage of the lesioned striatum and the concomitant enlargement of the lateral ventricles was visible on the precontrast MR images. Following administration of Gd-DTPA, there was no enhancement of any regions of the brain. Therefore, the structural perturbations of the striatum produced by KA lesions were not accompanied by disruption of the BBB. These studies demonstrate that MR imaging represents a useful technique for investigating in vivo the perturbation of the cerebral vasculature in rat models of neuropathologies. PMID- 1907879 TI - Outcomes of admission to a psychogeriatric service. AB - There is an increasing demand in Canada for improved care of elderly patients with psychiatric disorders. We report one year's experience, with a one year follow-up, of 130 consecutive admissions to the psychogeriatric service at Alberta Hospital, Edmonton. Approximately one-half of the patients came from the community and one-half from long term care institutions; 3 % were admitted via an acute care hospital. The median age was 76 years (range from 43 to 92). Aggression (45%) and wandering (29%) were the most common problems. Dementia was diagnosed in 58% and depression in 19% of patients; 17% had medical problems which precipitated or exacerbated the presenting symptoms. The median length of stay was 92 days (range from one to 365 days); patients admitted from long term care facilities were hospitalized for a longer period of time than those admitted from the community. The mortality rate was 16% in the hospital and five percent at one year follow-up. Approximately one-half of the patients were discharged back to their original residence. These results suggest that even very severely disturbed behaviour can be managed successfully and that a close link between medical diagnostic and treatment services is important. Innovations between these services and long term care facilities may reduce the need for prolonged hospitalization. PMID- 1907880 TI - SAD chart revisited. PMID- 1907881 TI - Evidence for the elevation of serum carcinoembryonic antigen and tumor-associated glycoprotein-72 levels in patients administered interferons. AB - Sera were collected from 111 patients diagnosed with adenocarcinoma or nonadenocarcinoma malignancies who received different schedules of interferon (IFN)-gamma or IFN-beta ser alone or in combination. Serum carcinoembryonic antigen (CEA) and tumor-associated glycoprotein-72 (TAG-72) antigen levels were measured to determine whether interferon could enhance the tumor shedding and, thereby, the serum level of either tumor antigen. Less than 10% of the sera samples from patients diagnosed with nonadenocarcinoma malignancies (e.g., hairy cell leukemia, melanoma) had positive titers of TAG-72 or CEA, and interferon neither increased nor resulted in the appearance of either tumor antigen in those sera. In contrast, 59.2% and 75.4% of the patients with adenocarcinoma had positive serum levels of TAG-72 and CEA, respectively, prior to interferon. IFN gamma and IFN-beta ser alone or in combination significantly increased serum TAG 72 or CEA in approximately 65% of those patients. The results suggest that interferon administration to patients with adenocarcinoma can result in increased serum levels of selected tumor-associated antigens used in the diagnosis of malignancy. These preliminary findings may be important in the development of new strategies to obtain more sensitive tumor antigen serum assays for the diagnosis and monitoring for disease progression of adenocarcinoma. PMID- 1907882 TI - Differences in the regulation of intracellular calcium in normal and neoplastic keratinocytes are not caused by ras gene mutations. AB - The development of resistance to terminal differentiation is an early event in epidermal neoplasia. Altered differentiation can be detected in vitro since normal epidermal cells are induced to differentiate in medium with Ca2+ greater than 0.1 mM while neoplastic epidermal cells and keratinocytes transduced with a v-rasHa gene are resistant to Ca2+. In normal epidermal cells, the elevation of extracellular Ca2+ (Cao) from 0.05 to 1.2 mM causes a biphasic intracellular Ca2+ (Cai) response in which a transient (10 min) peak of 4-5-fold over basal values is followed by a sustained (greater than 24 h) 2-fold increase in steady-state Cai. The transient peak in Cai is dependent on a serum component and independent of Cao, while the sustained plateau is directly dependent on Cao. The transient peak responding to a serum factor is lost in normal cells after 24 h in 1.2 mM Ca2+, a time when these cells are differentiating. Two neoplastic keratinocyte cell lines, SP-1 and 308, which produce benign tumors in vivo, also have a biphasic Cai response to an increase in Cao. In these cells, the transient peak is also serum dependent and amplified to 10-fold over basal values. However, the plateau value is not sustained and returns to basal values by 8 h, independent of Cao. Furthermore, 308 cells remain sensitive to the serum-induced Cai transient after 24 h in 1.2 mM Ca2+. To determine whether the activating c-rasHa mutation in 308 and SP-1 cells was responsible for the altered Cai regulation, a v-rasHa gene was introduced into normal keratinocytes by a defective retrovirus. This also produces the papilloma phenotype in vivo. Recipient cells were resistant to Ca(2+)-induced terminal differentiation although they did not proliferate in 1.2 mM Ca2+. The Cai profile in response to 1.2 mM Ca2+ was identical in normal and v rasHa keratinocytes, and these cells lost the serum-induced transient Cai peak after 24 h. Thus, the activation of the c-rasHa gene in 308 or SP-1 cells is probably not solely responsible for the altered Cai response in neoplastic cell lines. Sustained physiological elevation of Cai may be relevant to the loss of proliferative potential in both normal and v-rasHa keratinocytes in 1.2 mM Ca2+. In addition, v-rasHa-mediated or activated c-rasHa-mediated changes in a complementary pathway may contribute to the block in terminal differentiation in neoplastic cells. PMID- 1907883 TI - Bladder wall penetration of intravesical mitomycin C in dogs. AB - We examined the kinetics of penetration of mitomycin C (MMC) in the dog bladder wall after intravesical instillation of 20 mg/40 ml, a dose used in patients. Bladder tissues were harvested and concentration-depth profiles were established by analysis of thin tissue slices cut parallel to the urothelial surface of the bladder. Tissue concentrations after a dwell time of 5-7 min were similar to those after 30-120 min. In tissues harvested 60 and 75 min after removal of the dose, MMC was not detected in 5 of 6 samples and was less than 1 micrograms/g at the mucosa in the remaining sample, suggesting a rapid "washout" of the drug. The rapid equilibrium between the drug in urine and bladder tissue indicates that the duration of exposure of the bladder wall tissue was approximately equal to the dwell time of intravesical therapy. Tissue concentrations declined log-linearly with respect to the depth of penetration. The concentration immediately underneath the urothelium (C0) showed considerable intra- and interanimal variability. Bladder distention appeared to increase C0 by several fold. C0 ranged from 2 to 275 micrograms/g wet tissue weight, with a median value of 24 micrograms/g, or 11 micrograms/g when two animals with distended bladders were excluded. MMC concentrations in 3 different sites of the same bladder varied up to 5-fold. Within the capillary-perfused mucosa and muscularis (between 50 and 2000 microns from the urothelial surface), concentrations decreased by 50% for each 500-microns distance. The median concentration at 2000 microns was 1 microgram/g (n = 24). At 2000-3000 microns, tissue concentrations in most (18 of 24) specimens either declined to an asymptotic value or were lower than the detection limit of 0.1 microgram/g. Concentrations in the bladder contents were 200-500 micrograms/ml, the average tissue concentration from 50 to 3000 microns was 10 micrograms/g, and plasma concentrations were less than 0.1 microgram/ml. This supports the therapeutic advantage of intravesical therapy of high local drug concentrations while minimizing systemic exposure. A comparison of the urine concentration and C0 indicated a 30-fold decline in concentration across the urothelium. This suggests the importance of the urothelium as a barrier to MMC absorption. A separate study in our laboratories showed that 16 micrograms/ml of MMC was needed to produce a 90% inhibition of the labeling index of explants of human bladder cancers located in the urothelium (Ta tumor, TNM classification), 25 micrograms/ml in the lamina propria (T1 tumors), and 43 micrograms/ml in the muscle layer (T2 tumors).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1907885 TI - Association of hematuria and mycobacterial infection. AB - Hematuria has been noted to be a presenting symptom of urinary tuberculosis. In the last few decades because of the decreasing incidence of tuberculosis in the United States, the association of tuberculosis and hematuria has been neglected. Now that the incidence of tuberculosis is again on the rise, it is timely to remind the medical community of this association. We present 3 children with hematuria associated with positive tuberculin tests. Mycobacterium tuberculosis was cultured from the urine of one patient. Mycobacterium avium-intracellulare was cultured from a second patient. All 3 patients showed clearing of their hematuria with antituberculosis therapy. A tuberculin test should once again be considered part of the standard work-up of hematuria. PMID- 1907884 TI - Promoting effect of snuff in rats initiated by 4-nitroquinoline-N-oxide or 7,12 dimethylbenz(a)anthracene. AB - A canal was surgically created in the lower lip of male Sprague-Dawley rats and used as a reservoir for moist snuff. A total of 230 animals were randomized into six groups, five containing 40 rats and one containing 30 rats. After 2 wk of recuperation, the animals were treated as follows. Group I was initiated with 7,12-dimethylbenz(a)anthracene 3 times/wk for 4 wk followed by cotton pellet administration. Group II was initiated with 7,12-dimethylbenz(a)anthracene for 4 wk followed by snuff twice a day, 5 days/wk. Group III received snuff twice a day, 5 days/wk. Groups IV and V were initiated with 4-nitroquinoline N-oxide 3 days/wk for 4 wk. Thereafter Group IV received a cotton pellet, and Group V rats were treated with snuff twice a day, 5 days/wk. Group VI received a cotton pellet once a day, 5 days/wk. Treatment of all groups continued for a maximum of 104 wk. Group V rats had a significantly lower mean survival time than did the other groups because of the development of lip sarcomas in 66% of the rats as compared with 23% in Group II and 26% in Group III. One rat in each of Groups IV and VI developed lip sarcomas. The incidence of sarcomas in Group V as compared with the other groups is statistically significant (P less than 0.05 to 0.001). Spindle cell proliferation, a possible precursor lesion of lip sarcoma, was found in five rats of Group II, seven of Group III, and four of Group V. These results show that snuff has strong promoting capability with regard to the development of lip sarcomas after 4-nitroquinoline N-oxide initiation, but not after 7,12 dimethylbenz(a)anthracene initiation. Snuff by itself caused three squamous carcinomas of the palate, two squamous cell papillomas of the lip, and ten lip sarcomas (in 38 rats as compared with one lip sarcoma in 30 control rats), showing snuff to be carcinogenic for the lip and oral cavity. PMID- 1907886 TI - Synaptophysin immunoreactivity in the mammalian endocrine pancreas. AB - Synaptophysin, a major membrane glycoprotein of small presynaptic vesicles in neurons, has also been found in microvesicles of endocrine cells, e.g., of the endocrine pancreas. In the present study, the endocrine pancreas in 9 mammalian species (man, dog, mink, bovine, rabbit, guinea pig, rat, mouse, gerbil) has been investigated immunohistochemically for synaptophysin immunoreactivity. Synaptophysin-positive cells have been identified and localized on semithin plastic sections. Our study demonstrates that, in all species examined, all pancreatic endocrine cell types are consistently synaptophysin-positive independent of their location within the tissue, or the conditions of tissue processing. In addition, a few cells that cannot be hormonally identified show synaptophysin immunoreactivity. Hence, synaptophysin appears to be a regular constituent of all pancreatic endocrine cells in mammals. In several species, a subpopulation of endocrine cells, consisting of glucagon-containing and/or pancreatic-polypeptide-containing cells, exhibits a significantly higher degree of synaptophysin immunoreactivity. In the gerbil, this heterogeneity can readily be detected from the day of birth onwards. Our findings indicate that closely related endocrine cell types may differ with respect to the content of synaptophysin. PMID- 1907888 TI - Study in vitro of the phagocytic function of Sertoli cells in the rat. AB - Aspects of the interaction between residual bodies/cytoplasts from elongated spermatids (RB/CES) and Sertoli cells were studied in vitro. Highly enriched Sertoli cells (91%: experiment A), very highly enriched Sertoli cells (greater than 96%: experiment B), as well as peritubular cells were isolated from testes of 20-day-old rats by means of hypotonic treatment. Isolated Sertoli cells and peritubular cells were also prepared from 45-day-old rats (experiment C). RB/CES were isolated by centrifugal elutriation from testes of rats aged 90-120 days. The kinetics of adhesion of RB/CES to Sertoli cells were similar in all experiments. FSH accelerated binding of RB/CES but markedly reduced the number of RB/CES phagocytosed. Co-culture of the highly enriched Sertoli cells from experiments A and C with isolated peritubular cells did not change the kinetics of adhesion of RB/CES. However, when the contamination of Sertoli cells by peritubular cells was at a minimum (experiment B), addition of peritubular cells induced a slight but significant stimulation of the binding of RB/CES. Transmission electron microscopy revealed the following events within 24 h of co culture: adhesion of the RB/CES to microvilli of Sertoli cells; internalization of RB/CES; lysis of the membrane of RB/CES; total digestion. Therefore, FSH and peritubular cells modulate the interaction in vitro between Sertoli cells and RB/CES, and the different steps of residual body disposal can be reproduced in co culture. The co-culture model described in this study provides a useful system for the study of phagocytic activity by Sertoli cells. PMID- 1907887 TI - Myofibrillar and cytoskeletal assembly in neonatal rat cardiac myocytes cultured on laminin and collagen. AB - Neonatal rat cardiomyocytes were cultured on extracellular matrix components laminin and collagens I + III to examine effects of extracellular matrix on the assembly of cytoskeletal proteins during myofibrillogenesis. Myofibril assembly was visualized by immunofluorescence of marker proteins for myofibrils (f-actin for I bands and alpha-actinin for Z bands), focal adhesions (vinculin), and transmembrane extracellular matrix receptors (beta 1 integrin) as cells spread for various times in culture. By 4 h in culture, f-actin appeared organized into nonstriated stress-fiber-like structures while alpha-actinin, vinculin and beta 1 integrin were localized in small streaks and beads. Subsequently, striated patterns were observed sequentially in the intracellular cytoskeletal components alpha-actinin, vinculin, f-actin, and then in the transmembrane beta 1 integrin receptor. These data support an earlier model for sarcomerogenesis in which stress-fiber-like structures serve as initial scaffolds upon which alpha-actinin and then vinculin-containing costameres are assembled. This sequential and temporal assembly was the same on both laminin and collagens I + III. A quantitative difference, however, was apparent on the 2 matrices. There was an increased appearance on collagens I + III of rosettes (also called podosomes or cortical actin-containing bodies in other cells) which consisted of an f-actin core surrounded by alpha-actinin, vinculin and beta 1 integrin rims. The increased incidence of rosettes in neonatal myocytes on collagens I + III suggests that these cytoskeletal complexes are involved in recognition and interaction with extracellular matrix components. PMID- 1907889 TI - Role of neurogenic genes in establishment of follicle cell fate and oocyte polarity during oogenesis in Drosophila. AB - Oogenesis in Drosophila involves specification of both germ cells and the surrounding somatic follicle cells, as well as the determination of oocyte polarity. We found that two neurogenic genes, Notch and Delta, are required in oogenesis. These genes encode membrane proteins with epidermal growth factor repeats and are essential in the decision of an embryonic ectodermal cell to take on the fate of neuroblast or epidermoblast. In oogenesis, mutation in either gene leads to an excess of posterior follicle cells, a cell fate change reminiscent of the hyperplasia of neuroblasts seen in neurogenic mutant embryos. Furthermore, the Notch mutation in somatic cells causes mislocalization of bicoid in the oocyte. These results suggest that the neurogenic genes Notch and Delta are involved in both follicle cell development and the establishment of anterior posterior polarity in the oocyte. PMID- 1907890 TI - Isolation of coactivators associated with the TATA-binding protein that mediate transcriptional activation. AB - A key step in the regulation of transcription involves interactions between promoter-selective factors and various components of the transcriptional apparatus. Here we report the requirements for transcriptional activation directed by NTF-1, a developmentally regulated transcription factor in Drosophila. Reconstituted transcription with fractionated Drosophila basal factors reveals that activation by NTF-1 requires factors present in the endogenous TFIID fraction that are distinct from the purified TATA-binding protein (TBP). Glycerol gradient sedimentation and immunoprecipitation analyses indicate that TFIID is a multiprotein complex containing TBP and at least six tightly bound TBP-associated factors (TAFs). Preparations of TBP lacking TAFs after fractionation with denaturants no longer support activation by NTF-1 but retain basal level activity. Addition of immunopurified and renatured TAFs to free TBP restores the ability of NTF-1 to activate transcription without influencing basal transcription. These results suggest that one or more of the TAF polypeptides confer coactivator function. PMID- 1907892 TI - Differentiation of species and strains among filamentous fungi by DNA fingerprinting. AB - We have analyzed 11 strains and clones, representing five species (Penicillium janthinellum, P. citrioviridae, P. chrysogenum, Aspergillus niger, Trichoderma harzianum) and three genera of filamentous fungi, for the presence of hypervariable loci in their genomes by hybridization with simple repeat oligonucleotides and the DNA of phage M13. The oligonucleotide probes (CT)8, (GTG)5 and (GACA)4, as well as M13 DNA, are informative probes for fingerprinting in all genera and species tested. The probe (GATA)4 produced informative fingerprints only with the genomic DNA of A. niger. There was no similarity between the fingerprints originating from fungi of different genera and also little similarity between the fingerprints of different species belonging to the same genus. Fingerprints of strains of the same species differed only slightly from each other. Fingerprints of clones originating from one strain were identical. The results indicate that DNA fingerprinting is a powerful method to differentiate species and strains of filamentous fungi. PMID- 1907891 TI - RNA recognition by Tat-derived peptides: interaction in the major groove? AB - Replication of human immunodeficiency virus requires binding of the viral Tat protein to its RNA target sequence TAR; peptides derived from Tat bind to a TAR "contact site" spanning 5 bp and a trinucleotide pyrimidine bulge. We find that high affinity binding requires a U residue in the bulge loop and 2 specific adjacent base pairs. Other bulged RNAs bind in a lower affinity nonspecific manner; sequence-specific binding requires a bulge loop of more than 1 nucleotide. Reaction with diethyl pyrocarbonate indicates that one effect of the bulge is to make the otherwise deep and narrow RNA major groove accessible. A model consistent with these data involves local distortion of A-form geometry at the bulge, which bends the helix and permits protein binding and interactive access in the RNA major groove. PMID- 1907893 TI - rps10, unreported for plastid DNAs, is located on the cyanelle genome of Cyanophora paradoxa and is cotranscribed with the str operon genes. AB - rps10, encoding the plastid ribosomal protein S10, is a nuclear gene in higher plants and green algae, and is missing from the large ribosomal protein gene cluster of chlorophyll b-type plastids that contains components of the prokaryotic S10, spc and alpha operons. The cyanelle genome of Cyanophora paradoxa is shown to harbor rps10 as another specific feature of its organization. However, this novel plastid gene is not contiguous with the genes of the "S10" operon, but is adjacent to, and cotranscribed with, the str operon, a trait also found in archaebacteria. PMID- 1907895 TI - Lethal(1) aberrant immune response mutations leading to melanotic tumor formation in Drosophila melanogaster. AB - Using P element-mediated mutagenesis we have isolated 20 X-linked lethal mutations, representing at least 14 complementation groups, which exhibit melanotic tumor phenotypes. We present the systematic analysis of this interesting group of lethal mutations that were selected for their visible melanotic or immune response. The lethal and melanotic tumor phenotypes of each lethal(1) aberrant immune response (air) mutation are pleiotropic effects of single genetic lesions. Lethality occurs throughout the larval and early pupal periods of development and larval development is extended in some air mutants. The air mutant lethal syndromes include abnormalities associated with the brain, haematopoietic organs, gut, salivary glands, ring glands, and imaginal discs. Additional characterization of the melanotic tumor mutations Tuml and tu(1)Szts have indicated that the melanotic tumor phenotype is similar to that observed in the air mutants. These studies have led to the proposal that two distinct classes of melanotic tumor mutations exist. Class 1 includes mutants in which melanotic tumors result from "autoimmune responses" or the response of an apparently normal immune system to the presence of abnormal target tissues. The Class 2 mutants display obvious defects in the haematopoietic organs or haemocytes, manifested as overgrowth, and the resulting aberrant immune system behavior may contribute to melanotic tumor formation. PMID- 1907894 TI - Monoclonal and oligoclonal gammopathies in heart-transplant recipients. AB - Immunoglobulin abnormalities in serum from 76 heart-transplant recipients were examined by cellulose acetate and agarose gel electrophoresis. Monoclonal components were typed by immunofixation. IgG, IgA, and IgM and total kappa and lambda light chains were quantified by immunonephelometry. We confirm that both monoclonal and oligoclonal immunoglobulin banding are common in serum from these patients. Of the 149 serum samples examined, 21 (15%) had one monoclonal component and 53 (35%) had two or more. These monoclonal immunoglobulins were generally present at a low concentration and were transient. The class of immunoglobulins most commonly involved was IgG (about sevenfold more numerous than IgM); monoclonal IgA components and free light chains were not detected. The nephelometric kappa/lambda and heavy chain/light chain ratios were poor indicators of these abnormalities. Immunoglobulin abnormalities were not correlated with the sex and age of recipients, the pre-existing cardiopathy, the time since transplantation, or plasma concentrations of cyclosporine, but did correlate with plasma immunoglobulin concentration, biopsy findings, and viral infections, especially cytomegalovirus (CMV). A monoclonal IgG purified from a patient with a high titer of anti-CMV antibodies did not react with CMV antigens. The origin of these immunoglobulin abnormalities is unclear. Our data suggest that the presence of monoclonal or oligoclonal banding in heart-transplant recipients is of limited prognostic significance. PMID- 1907896 TI - Differential expression and isozymic composition of sn-glycerol-3-phosphate dehydrogenase in tissues from variant lines of Drosophila melanogaster. AB - The tissue-specific expression and isozymic composition of Drosophila sn-glycerol 3-phosphate dehydrogenase (GPDH) (EC 1.1.1.8) have been determined for a high activity control line and two variant lines that alter either the temporal or systemic expression of GPDH through a reduction in rates of polypeptide synthesis. The temporal variant exhibits a reduction in enzyme levels in all larval tissues and in the adult abdomen, while levels of activity in the adult thorax are equal to the control line. Isozymic analyses of these tissues demonstrate that it is the GPDH-3 species that is reduced in a temporal and tissue-specific manner. In contrast, the systemic variant demonstrates a uniform reduction of all isozymic species in each tissue and developmental stage. Analyses of the tissues of F1 hybrid offspring of each variant line and appropriately marked electrophoretic variants demonstrate that the tissue specific effects observed are due to cis-acting elements that are tightly linked to the structural gene. PMID- 1907897 TI - Maternal immunization to prevent fetal and neonatal infection. PMID- 1907898 TI - Tc-99m HMPAO SPECT of the brain in a patient with striopallidodentate calcifications. AB - CT scan in a 52-year-old woman, admitted because of grand mal seizure, showed striopallidodentate calcifications due to postoperative hypoparathyroidism. This patient report stresses the possibility of cortical metabolic involvement in this disorder, as shown on Tc-99m HMPAO brain SPECT, despite the absence of cognitive defects. PMID- 1907899 TI - Function of the carbohydrates in contact site A glycoprotein of Dictyostelium discoideum affected by tunicamycin. AB - 1. The relationship between glycosylation of contact site A (csA) of 80 kDa with two types of N-linked carbohydrates, I and II, and EDTA-resistant cell contact of Dictyostelium was investigated by tunicamycin treatment. 2. Carbohydrate I glycosylation, involved in a shift of csA from 66 to 80 kDa, was more sensitive to tunicamycin than carbohydrate II glycosylation in its shift from 53 to 66 kDa. 3. The appearance of csA of 80 kDa corresponded to that of EDTA-resistant cell contact. Carbohydrate I may be essential for EDTA-resistant cell contact. 4. In starved cells treated with tunicamycin, only 4-8% of moieties labeled with wheat germ agglutinin in carbohydrate II were modified. PMID- 1907900 TI - Polyol pathway in tissues of spontaneously diabetic Chinese hamsters (Cricetulus griseus) and the effect of an aldose reductase inhibitor, ONO-2235. AB - 1. Sorbitol and fructose levels were significantly elevated in the lens, the sciatic nerve, the retina and the kidney of diabetic Chinese hamsters and inositol level was significantly decreased in the lens and sciatic nerve of diabetics. 2. The activity of an aldose reductase in the kidney was not different between normal and diabetic Chinese hamsters. 3. An aldose reductase inhibitor (ONO-2235) had no effect in sorbitol, fructose and inositol contents of all these tissues from diabetic Chinese hamsters. 4. These results suggest that diabetic Chinese hamsters produce polyol accumulation in tissues but that there is a clear species-specific difference to inhibition of aldose reductase. PMID- 1907901 TI - Post-cardiac transplant reactivation of Chagas' disease diagnosed by skin biopsy. AB - Reactivation of Chagas' disease in immuno-compromised hosts may represent a recognizable clinical syndrome that can be diagnosed by examination of skin biopsy specimens of characteristic lesions resembling ordinary bacterial cellulitis. This syndrome appears to result in significant morbidity, which can be avoided with the institution of prophylactic therapy for Chagas' disease. An awareness of this complication of immunosuppression is of paramount importance for the thousands of asymptomatic persons infected with Chagas' disease currently living in the United States and abroad. PMID- 1907902 TI - Action of actinomycin D on glycosidase levels in the small intestine of hamsters. AB - Actinomycin D affects a number of functions of the epithelial cells of the small intestine. Maltase, saccharase and lactase levels in the small intestine of hamsters treated with various dosages of actinomycin D over various periods of time, differed from those observed in control animals: administration of 0.25 micrograms/g body weight, gave rise to a statistically significant increase in the maltase and saccharase levels measured after 4 h and a statistically significant reduction in the lactase levels measured after 8 h; administration of 1.5 micrograms/g body weight reduced the activity of all three enzymes at all times post-administration, the decrease being statistically significant for maltase after 2 and 8 h. PMID- 1907903 TI - [Opioid peptides in cerebrospinal fluids of epileptic patients]. AB - By means of RIA, the contents of Leu-enkephalin, Met-enkephalin, and Beta endorphin in CSF of 32 epileptic patients and 24 controls were determined. It was found that the mean Leu-enkephalin content in CSF of the epileptic patient group was significantly higher than that of the control group (P less than 0.01), whereas the mean contents of Met-enkephalin and Beta-endorphin in CSF showed no significant change as compared with those of the control group. The increase of Leu-enkephalin was not related to such factors as type of seizure, age of onset, length of time after the last seizure, taking of antiepileptic drugs, and abnormality in cranial CT manifestation. This suggested that endogenous opioid peptides might take part in the neurochemical mechanism of human epilepsy, and leu-enkephalin could play an important role in the development of epileptic episodes. PMID- 1907904 TI - Carbaryl-induced thyroid dysfunction in the freshwater catfish Clarias batrachus. AB - Freshwater female catfish, Clarias batrachus, were exposed to sublethal concentrations of carbaryl (12 mg/liter for 96 hr and 5 mg/liter for 16 days) during the prespawning and spawning phases of their annual reproductive cycle. The effects on the levels of thyroxine (T4) and triiodothyronine (T3), the T3/T4 ratio, and the extrathyroidal conversion of T4 to T3 were studied in serum, pharyngeal thyroid, and anterior and posterior kidney. Carbaryl exposure for 96 hr suppressed T4 but elevated T3 and the T3/T4 ratio in serum during both phases of experimentation. However, 16 days exposure caused a decline in T4 as well as in T3 and in the T3/T4 ratio. In the pharyngeal thyroid, carbaryl increased T4 as well as peroxidase activity and decreased T3 and the T3/T4 ratio. Its treatment for 96 hr did not elicit any change in the parameters studied in the anterior kidney, whereas in the posterior kidney it suppressed the levels of T4 and T3, peroxidase activity, and the T3/T4 ratio. However, carbaryl exposure for 16 days provoked increases in T4 and peroxidase activity but decreases in T3 and the T3/T4 ratio in anterior kidney. In posterior kidney, it did not change T4 and peroxidase activity, but decreased T3 and the T3/T4 ratio. It also stimulated extrathyroidal conversion of T4 to T3. PMID- 1907905 TI - Intracranial, intraaxial, space-occupying lesions in patients with intractable partial seizures: an anatomoclinical, neuropsychological, and surgical correlation. AB - Fifty of approximately 250 patients evaluated for intractable partial seizures were shown to have a space-occupying lesion detected with radiographs and/or neuroimaging. Twenty-eight males and 22 females had a mean age at seizure onset of 13 years and a mean duration of seizures of 11 years. All patients had closed circuit television with EEG monitoring and complete neurologic and neuropsychological assessment. Findings were correlated with lesion location and surgical data. Twenty-seven lesions (54%) were located in the temporal lobe. Thirty-five lesions (70%) were neoplastic. All patients with temporal lobe lesions had complex partial seizures, as did 74% of patients with extratemporal lesions. A good correlation between clinical seizure characteristics and lesion localization was found with the temporal, occipital, and frontal lesions but not with the parietal lesions. Sixty-six percent of patients had focal interictal EEG findings. Lateralization corresponded to the side of the lesion in 64% and was localized to the region of the lesion in 30%. Lateralized ictal EEGs occurred in 58% of patients, corresponding with the side of the lesion in all but one patient. Abnormal findings on neuropsychological testing were congruent with lesion lateralization in 56% of patients and were localized to the region in 26%. Thirty-nine of 47 patients who underwent a subtotal lobectomy to include the lesion are seizure-free after greater than or equal to 1 year of follow-up, and five others are markedly improved. PMID- 1907906 TI - Surgical versus medical treatment for epilepsy. II. Outcome related to social areas. AB - We conducted a retrospective parallel cohort study comparing surgical and medical treatment for epilepsy. The surgical group contained all 201 patients treated with resective surgery for epilepsy in Norway since the first operation in 1949 until January 1988. The 185 patients in the control group, medically treated only, were closely matched for year of treatment, age at treatment, sex, seizure type, and neurologic deficit before treatment. Between 75 and 95% of the survivors (median 17 years after treatment) completed two questionnaires on their social situation. Although surgical treatment improved the seizure situation (about one-fourth had some neurologic deficit), a considerably smaller long-range influence on different social aspects was observed. There were no significant differences between the two groups in educational status, social pensions, social status, marital status, fertility, dependency in residential situation, the need for aid in daily activities of living (ADL), or the need for being looked after, when we controlled for pretreatment status. In all, 25.3% of the surgically treated patients and 8.5% of the controls were not receiving anti-epileptic drugs (AEDs) at the time of investigation (Mann-Whitney U test, two-tailed p = 0.0011). A considerably higher proportion of the surgically treated (53.2%) than control patients (24.2%) claimed that the treatment had improved their "working ability" (Mann-Whitney U test, two-tailed p less than 0.0001), but this resulted in significant improvements in the actual working situation only for those in regular education or work before treatment (chi 2 = 6.514, p = 0.038). PMID- 1907907 TI - Double-blind study of Gabapentin in the treatment of partial seizures. AB - Forty-three patients completed a double-blind, placebo-controlled study of Gabapentin (GBP) as add-on therapy in partial and secondarily generalized seizures. All patients were followed for an initial 3-month baseline period, after which they were randomly allocated to receive either a placebo or 900 or 1,200 mg/day GBP for 3 months. A statistically significant difference in seizure frequency from the baseline to the treatment phase was noted between patients receiving placebo and GBP 1,200 mg, in whom seizure frequency decreased 57%. The GBP dosage of 900 mg appeared to be ineffective. A close relationship was observed between the serum GBP concentrations and the GBP dosage based on the seizure frequency. Serum GBP concentrations greater than 2 micrograms/ml resulted in a lower frequency of seizures. The adverse effects were minor and consisted mainly of transient drowsiness. GBP appears to be effective in the treatment of partial epileptic seizures in a dosage-related manner. PMID- 1907909 TI - The role of technical, biological and pharmacological factors in the laboratory evaluation of anticonvulsant drugs. III. Pentylenetetrazole seizure models. AB - Although seizure models using systemic administration of the chemoconvulsant pentylenetetrazol (PTZ) for induction of generalized clonic seizures in rodents are widely employed to identify potential anticonvulsants, the important role of diverse technical, biological and pharmacological factors in interpretation of results obtained with these models is often not recognized. The aim of this study was to delineate factors other than sex, age, diet, climate, and circadian rhythms, which are generally known. For this purpose, experiments with 8 clinically established antiepileptic drugs were undertaken in the following PTZ models: (1) the threshold for different types of PTZ seizures, i.e., initial myoclonic twitch, generalized clonus with loss of righting reflexes, and tonic backward extension of forelimbs (forelimb tonus), in mice; (2) the traditional PTZ seizure test with s.c. injection of the CD97 for generalized clonic seizures in mice; and (3) the s.c. PTZ seizure test in rats. In rats, in addition to evaluating drug effects on generalized clonic seizures, a ranking system was used to determine drug effects on other seizure types. When drugs were dissolved in vehicles which themselves did not exert effects on seizure susceptibility, the most important factors which influenced drug potencies were: (1) bishaped dose response curves, i.e., a decline in anticonvulsant dose-response at high doses of some drugs, leading to misinterpretations of drug efficacy if only a single high drug dosage is tested; (2) effects of route of PTZ administration (i.v. infusion vs. s.c. injection) on estimation of anticonvulsant potency; (3) species differences in drug metabolism; (4) differences in drug potencies calculated on the basis of administered doses compared to potency calculations based on 'active' drug concentrations in plasma; (5) qualitative and quantitative species differences in drug actions; (6) endpoints used for PTZ tests; (7) misleading predictions from PTZ seizure models. Analysis of anticonvulsant drug actions indicated that myoclonic or clonic seizures induced by i.v. or s.c. PTZ might be suitable for predicting efficacy against myoclonic petit mal seizures in humans, but certainly not to predict efficacy against absence seizures. Tonic seizures induced by PTZ were blocked by drugs, such as ethosuximide, which exert no effect on tonic seizures in humans. In order to reduce the variability among estimates of anticonvulsant activity in PTZ seizure models, the various factors delineated in this study should be rigidly controlled in experimental situations involving assay of anticonvulsant agents. PMID- 1907908 TI - Effects of pyrethroid insecticides on hepatic microsomal enzymes in rats. AB - The effects of pyrethroid insecticides on hepatic microsomal enzymes were studied in rats. Animals were treated orally with cypermethrin (80 mg/kg), deltamethrin (15 mg/kg), and permethrin (100 mg/kg), as a solution in soyabean oil, for 1 to 20 days. The content of cytochromes P-450 and b5, activity of NADPH cytochrome P 450 reductase, glutathione S-transferase, aniline 4-hydroxylase, p-nitroanisole O demethylase in microsomes, the activity of glutathione S-transferase, and the level of sulfhydryl groups in cytosol were determined. Also the relative liver weight was measured. Only few changes in the investigated parameters were ascertained. These changes have an irregular and transient character. On the whole, the action of pyrethroids on microsomal enzymes results in a slight induction. PMID- 1907910 TI - A serial study of regional cerebral blood flow before and after hemispherectomy in a child. AB - Hemimegalencephaly (HME) is a severe unilateral brain malformation the prognosis of which may be improved by hemispherectomy. HME also provides a unique opportunity to compare normal and pathological hemispheric function in the same patient. We performed a serial functional cerebral imaging study in a child suffering from a neuropathologically confirmed left HME. He was hemispherectomized at 11 months because of intractable epilepsy; this led to cessation of seizures and dramatic psychomotor improvement. Regional cerebral blood flow (rCBF) was studied at 1, 7, 10, 12 and 25 months with single photon computed tomography (SPECT) using 133-Xenon and with simultaneous EEG recording. At one month of age SPECT was performed ictally. During left EEG discharges, rCBF was 40% higher on the left hemisphere than on the right, even in occipital and frontal regions, usually immature at this age. A crossed cerebellar hyperperfusion was also found. At 7 and 10 months, SPECT was performed interictally; rCBF was 45% lower in the left hemisphere than in the right. During follow-up, global and regional CBF values showed normal levels and normal maturation in the right hemisphere except for a mild and transient decrease observed one month after hemispherectomy. SPECT provides an additional procedure for studying hemispheric function in vivo. Serial SPECT imaging may be useful for the preoperative and postoperative evaluation in unilateral cerebral malformation. PMID- 1907911 TI - The ontogeny of diversification at the immunoglobulin heavy chain locus in Xenopus. AB - Since the larval and adult antibody responses are distinct and restricted in the clawed toad Xenopus, it offers a near ideal model for studying the ontogeny of antibody repertoires and the mechanisms involved. Immunoglobulin heavy chain (IgH) cDNA clones and B cell IgH DNA clones from various larval and adult libraries have been analysed in isogenic Xenopus. Some features are similar in adults and tadpoles, while others differ and explain the particularities observed previously at the protein level. Among the similarities we found are: (i) the mode of rearrangements (there are approximately 50% abortive events in B cells from both stages), (ii) VH family usage (10 of 11 known VH families are expressed proportionally to the number of VH elements per family), and (iii) JH usage (of the eight to nine Xenopus JH elements, two are used in approximately 70% of the VH regions in both stages of development). We found that there is relatively higher membrane exon expression in tadpoles compared with adults; and that most of the differences come from the diversification of CDR3 through DH usage and N diversification. Unlike in mammals, Xenopus DH elements are used with a remarkable flexibility with inversion, fusions and usage in different reading frames, but tadpoles show a strong bias for the usage of only a few DH elements and of a preferred reading frame. There is N diversification, which further increases CDR3 heterogeneity, in adult Xenopus but virtually none in tadpoles. These observations can account for the fact that larval antibody responses are less heterogeneous than those of adults. PMID- 1907912 TI - Muscle-specific accumulation of Drosophila myosin heavy chains: a splicing mutation in an alternative exon results in an isoform substitution. AB - We show that the molecular lesions in two homozygousviable mutants of the Drosophila muscle myosin heavy chain gene affect an alternative exon (exon 9a) which encodes a portion of the myosin head that is highly conserved among both cytoplasmic and muscle myosins of all organisms. In situ hybridization and Northern blotting analysis in wild-type organisms indicates that exon 9a is used in indirect flight muscles whereas both exons 9a and 9b are utilized in jump muscles. Alternative exons 9b and 9c are used in other larval and adult muscles. One of the mutations in exon 9a is a nonsense allele that greatly reduces myosin RNA stability. It prevents thick filament accumulation in indirect flight muscles and severely reduces the number of thick filaments in a subset of cells of the jump muscles. The second mutation affects the 5' splice site of exon 9a. This results in production of an aberrantly spliced transcript in indirect flight muscles, which prevents thick filament accumulation. Jump muscles of this mutant substitute exon 9b for exon 9a and consequently have normal levels of thick filaments in this muscle type. This isoform substitution does not obviously affect the ultrastructure or function of the jump muscle. Analysis of this mutant illustrates that indirect flight muscles and jump muscles utilize different mechanisms for alternative RNA splicing. PMID- 1907913 TI - The doublesex proteins of Drosophila melanogaster bind directly to a sex-specific yolk protein gene enhancer. AB - The doublesex (dsx) gene of Drosophila melanogaster encodes both male-specific and female-specific polypeptides, whose synthesis is regulated by alternative sex specific splicing of the primary dsx transcript. The alternative splicing of the dsx mRNA is the last known step in a cascade of regulatory gene interactions that involves both transcriptional and post-transcriptional mechanisms. Genetic studies have shown that the products of the dsx locus are required for correct somatic sexual differentiation of both sexes, and have suggested that each dsx product functions by repressing expression of terminal differentiation genes specific to the opposite sex. However, these studies have not shown whether the dsx gene products function directly to regulate the expression of target genes, or indirectly through another regulatory gene. We report here that the male- and female-specific DSX proteins, expressed in E.coli, bind directly and specifically in vitro to three DNA sequences located in an enhancer region that regulates female-specific expression of two target genes, the yolk protein genes 1 and 2. This result suggests strongly that dsx is a final regulatory gene in the hierarchy of regulatory genes controlling somatic sexual differentiation. PMID- 1907914 TI - Properties of the elongation factor 1 alpha in the thermoacidophilic archaebacterium Sulfolobus solfataricus. AB - The elongation factor 1 alpha (aEF-1 alpha) was purified to homogeneity from the thermoacidophilic archaebacterium Sulfolobus solfataricus by chromatographic procedures utilising DEAE-Sepharose, hydroxyapatite and FPLC on Mono S. The purified protein binds [3H]GDP at a 1:1 molar ratio and it is essential for poly(Phe) synthesis in vitro; it also binds GTP but not ATP. These findings indicate that aEF-1 alpha is the counterpart of the eubacterial elongation factor Tu (EF-Tu). Purified aEF-1 alpha is a monomeric protein with a relative molecular mass of 49,000 as determined by SDS/PAGE and by gel filtration on Sephadex G-100; its isoelectric point is 9.1. The overall amino acid composition did not reveal significant differences when compared with the amino acid composition of eubacterial EF-Tu from either Escherichia coli or Thermus thermophilus, of eukaryotic EF-1 alpha from Artemia salina or of archaebacterial EF-1 alpha from Methanococcus vannielii. The close similarities between the average hydrophobicity and the numbers of hydrogen-bond-forming or non-helix-forming residues suggest that common structural features exist among the factors compared. aEF-1 alpha shows remarkable thermophilic properties, as demonstrated by the rate of [3H]GDP binding which increases with temperature, reaching a maximum at 95 degrees C; it is also quite heat-resistant, since after a 6-h exposure at 60 degrees C and 87 degrees C the residual [3H]GDP-binding ability was still 90% and 54% of the control, respectively. The affinity of aEF-1 alpha for GDP and GTP was also evaluated. At 80 degrees C Ka' for GDP was about 30-fold higher than Ka' for GTP; at the same temperature Kd' for GDP was 1.7 microM and Kd' for GTP was 50 microM; these values were 300-fold and 100-fold higher, respectively, than those reported for E. coli EF-Tu at 30 degrees C; compared to the values at 0 degree C of EF-Tu from E. coli and T. thermophilus or EF-1 alpha from A. salina, pig liver and calf brain, smaller differences were observed with eukaryotic factors.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1907915 TI - Central neurofibromatosis. Case report and review of the literature. AB - An unusual case of central neurofibromatosis associated with a unilateral acoustic neuroma, multiple intracranial meningiomas, spinal neurofibroma and visceral involvement is presented. The progressive clinical course of this syndrome is described and discussed with a review of the relevant literature. PMID- 1907916 TI - Differential in situ expansion and gene expression of CD4+ and CD8+ tumor infiltrating lymphocytes following adoptive immunotherapy in a murine tumor model system. AB - In previous reports, we demonstrated that adoptively transferred T cells homed to the tumor site (among other sites) and that amplification of immune responses occurred in situ leading to the generation of cytotoxic CD8+ tumor-infiltrating lymphocytes (TIL) and macrophages. The present report extends these findings and shows that following adoptive immunotherapy (AIT) of mice bearing the immunogenic transplanted methylcholanthrene-induced rhabdomyosarcoma (MCA/76-9) there was a differential expansion of CD4+ and CD8+ TIL, the numbers peaking on days 6 and 8, respectively. At this time, CD8+ TIL accounted for the majority of Thy-1+ cells. Northern analyses of RNA extracted from positively selected (by panning) Thy-1+, CD8+ and CD4+ TIL isolated 8 days after AIT indicated the following: in five separate experiments, CD4+ cells expressed three- to sixfold more interleukin (IL)2 mRNA and six- to eightfold more IL6 mRNA than CD8+ cells, while CD8+ TIL expressed three- to sixfold more IL2 receptor (IL2R) mRNA and four- to sixfold more interferon-gamma mRNA than CD4+ cells. TIL cultured in 10% fetal bovine serum failed to release IL2 over a 24-h period, whereas both IL6 and interferon gamma activities were demonstrable. The level of IL2R mRNA expression was reflected by a vigorous proliferative response of CD8+ TIL to exogenous recombinant IL2 and only a low response by CD4+ cells suggesting that most of the CD4+ TIL were in the resting stage. This was confirmed when it was shown that the incubation of panned CD4+ TIL with IL2 supplemented with irradiated spleen cells and "spent" 76-9 tumor culture supernatant (as a source of antigen) induced expansion of TIL resulting in a population consisting of greater than 90% CD4+ TIL. The overall data suggest that the relatively deactivated state of the CD4+ TIL at this particular time reflects the status of the rejection process in terms of the absence or low concentration of stimulating tumor-associated antigen. PMID- 1907918 TI - Framework peptides from kappa IIIb rheumatoid factor light chains with binding activity for aggregated IgG. AB - Most monoclonal human rheumatoid factors (RF) and some RF from rheumatoid patient's synovia are restricted in their light chains, using predominantly the kappa IIIb subfamily. Very few sequence differences are found between these light chains. Light chains with similar variable region framework sequences are also found in some mouse monoclonal RF derived from mice stimulated with lipopolysaccharide or secondarily immunized with protein antigens. There are two likely explanations for this restriction in framework sequences between the two species: (a) the sequences are important for the immunoregulation of RF production or (b) the sequences are concerned with the antibody binding specificity of the RF. We have examined overlapping octapeptides from the kappa IIIb light chain variable region and show that some framework peptides have the ability to bind aggregated IgG. Replacement of amino acids within the peak binding peptide have indicated the critical amino acids necessary for binding. PMID- 1907917 TI - The human immunoglobulin kappa locus. Characterization of the duplicated O regions. AB - Two large regions of the human immunoglobulin kappa locus, the so-called O regions, have been characterized on cosmid and phage lambda clones. The two regions are very similar but not identical duplicates belonging to the C kappa proximal (p) and the distal (d) copies of the kappa locus. The Op and Od regions comprise contigs of 90 and 120 kb, respectively, and contain 20 V kappa genes and pseudogenes which have been sequenced. Three pairs of V kappa genes were found to be practically identical in the duplicates while allotypic differences, at least for two of the genes, are considerable. The similarities between the duplicate genes may be related to the fact that the two copies of the kappa locus are arranged in a palindrome-like fashion with the 5' sides of the O regions pointing towards each other (C kappa J kappa B Lp Ap Op-Od Ad Ld). This may have contributed to equalizing the sequences. Beyond Op and Od no further V kappa genes were found within about 80 kb. Instead, repetitive DNA sequences have been localized there, the structures of which suggest that they may have been involved in the evolution of the V kappa gene-containing regions. The V kappa pseudogene containing W regions, that had been transposed in evolution from the short to the long arm of chromosome 2 by a pericentric inversion, may have been derived from the O regions according to structural homologies between defined sections of the O and W regions. PMID- 1907919 TI - Components of an antigen-/T cell receptor-independent pathway of lymphokine production. AB - The general way to induce the synthesis of lymphokines by T cells is the stimulation through the T cell receptor (TcR) complex which results in an increase of intracellular [Ca2+] and in the activation of a tyrosine kinase as well as of protein kinase C. Lymphokine production induced via the TcR is inhibited by the immunosuppressive drug cyclosporin A (CsA). However, an alternative pathway of lymphokine production exists. Several T lymphocyte clones can synthesize interferon-gamma (IFN-gamma), granulocyte-monocyte colony stimulating factor, and small amounts of interleukin (IL3) when stimulated with syngeneic or allogeneic accessory cells (AC) plus IL2. In contrast to the TcR pathway the alternative pathway does not require a rise of intracellular [Ca2+] and is insensitive to the effects of CsA. In this report we provide evidence for the involvement of T cell-stimulating factor (TSF)--a probably novel murine cytokine--in the alternative pathway of lymphokine production. It is shown that fixation of the AC with carbodiimide or treatment of the AC with UV light greatly reduces their capacity to induce (in combination with IL2) the synthesis of IFN gamma by T cells. This function is restored by addition of TSF. Moreover, TSF alone (without IL2) in combination with fixed AC can induce the synthesis of substantial amounts of IFN-gamma. Furthermore, TSF in combination with IL2 can stimulate freshly isolated spleen cells to produce IFN-gamma. The target cell resides probably in the non-B cell, non-T cell population. PMID- 1907921 TI - Clonal expansion precedes anergy and death of V beta 8+ peripheral T cells responding to staphylococcal enterotoxin B in vivo. AB - Staphylococcal enterotoxin B (SEB) selectively stimulates T cells bearing T cell receptor V beta 8 domains and hence provides a useful model to study immunity and tolerance in vivo. We show here that V beta 8+ T cells in both CD4+ and CD8+ subsets expand dramatically (fivefold) in lymphoid tissues of mice 2-4 days following injection with SEB. This initial clonal expansion, which is accompanied by a transient hyper-reactivity to SEB, is followed by a rapid decrease in V beta 8+ cells and a concomitant induction of specific non-responsiveness which persists for at least 30 days. Selective death of V beta 8+ cells occurs during this latter phase. Taken together, our data indicate that clonal expansion, anergy and death can occur as sequential stages of an immune response in vivo. PMID- 1907920 TI - Production of interleukin 2 and interleukin 4 by immune CD4-CD8+ and their role in the generation of antigen-specific cytotoxic T cells. AB - In this report we investigated the production and role of interleukin (IL)2 and IL4 in the generation of antigen-specific cytotoxic T cells (CTL). We used as our model the ultraviolet-light-induced epithelial tumor 1591, a highly immunogenic regressor tumor which evokes a strong cell-mediated immune response leading to rejection. We show that IL2 and IL4 are differentially required for the development of optimal cytolytic activity to the 1591 tumor in primary and secondary in vitro splenic cultures. First, anti-IL2 receptor monoclonal antibody (mAb) significantly decreased specific cytotoxicity in both primary and secondary splenic mixed lymphocyte-tumor cell culture (MLTC) cultures, but anti-IL4 mAb inhibited the cytotoxic responses only secondary and not primary cultures. Second, when supernatants from MLTC were tested for lymphokine activity, primary cultures produced only IL2 while secondary cultures produced both IL2 and IL4. Splenic cells were then depleted of CD4+ cells by negative selection, or enriched for CD8+ cells by positive selection, and tested for lymphokine production and requirements. CD8+ cells could not generate significant CTL activity in primary cultures, but could in secondary MLTC. The addition of mAb to either IL2 or IL4 significantly inhibited the generation of CTL by CD8+ cells in these secondary MLTC.CD8+ cells were also found to produce both IL2 and IL4 in secondary MLTC by functional and Northern blot analysis. The production of IL2 and IL4 by CD8+ cells occurs during different phases of culture, with IL2 being produced early (days 1 and 2) and IL4 late (days 3-5). In addition, the requirement of CD8+ cells for both IL2 and IL4 is unique for that lymphokine. These results suggest that both IL2 and IL4 are both produced and required by CD8+ cells during secondary MLTC, and suggest an additional cellular source of IL4 production besides CD4+ T cells during antigen-specific CTL responses. PMID- 1907922 TI - Buprenorphine and morphine cause antinociception by different transduction mechanisms. PMID- 1907923 TI - Increased ion traffic through non-specific cation pathways in the ageing human lens. Evidence from radiotracer fluxes studies. AB - 86Rb efflux studies were carried out on normal human lenses in vitro. The data confirmed previous studies showing that 86Rb efflux increases with age. Removal of Ca2+ from the lens perifusate increased 86Rb efflux at all ages. The fractional increase above baseline was highest in the younger lenses, while the net increase of the 86Rb efflux induced by a Ca(2+)-free medium increased with age. This study supports the idea that Ca(2+)-sensitive, non-specific cation channels are present in the human lens and that their contribution to membrane permeability increases as the lens ages. PMID- 1907924 TI - Polyol accumulation in cultured human lens epithelial cells. AB - Human lens epithelial (HLE) cells in tissue culture accumulated significant levels of galactitol when they were cultured for 72 hr in medium containing 30 mM D-galactose. Polyol accumulation was accompanied by the appearance of vacuoles as seen by transmission electron microscopy. The number and size of intracellular vacuoles increased when the culture period was extended to 7 days. In addition, polyol accumulation was accompanied by loss of myoinositol. None of these changes occurred in cells exposed to 30 M L-galactose which is not a substrate for aldose reductase. The accumulation of galactitol, intracellular vacuole formation and loss of myoinositol observed in D-galactose-exposed cells were prevented by the inclusion of the aldose reductase inhibitor, sorbinil, in the culture medium. Comparison of the relative efficacies of two aldose reductase inhibitors indicate that AL 1576 is nearly 20 times more potent than sorbinil in inhibiting the human lens enzyme. It is concluded that vacuole formation in HLE cells is due to the osmotic effect of polyol formation brought about by the action of aldose reductase and that the etiology of human diabetic cataract may also involve the polyol pathway. PMID- 1907925 TI - Efficacy of recombinant human macrophage colony-stimulating factor in combination with whole-body hyperthermia in the treatment of mice infected with the polycythemia-inducing strain of the Friend virus complex. AB - Macrophage colony-stimulating factor (M-CSF, CSF-1) and whole-body hyperthermia (WBH) were evaluated, alone or in combination, for their capability to influence disease progression in mice inoculated with the polycythemia-inducing strain of the Friend virus complex (FVC-P). DBA/2 mice were injected i.v. with FVC-P and were treated with 20 micrograms/dose M-CSF s.c. twice a day for 5 days beginning 6 days after injection of FVC-P and/or with WBH (between 38.8 degrees C and 40.2 degrees C) given on days 5 and 12 after FVC-P injection. Fourteen days after viral inoculation, mice were sacrificed and spleen cells evaluated for: 1) spleen focus-forming virus (SFFV), by the spleen focus-forming unit assay (SFFU); 2) SFFV mRNA and genomic DNA using, respectively, Northern and Southern analysis with a B-E-SFFV DNA probe; and 3) natural killer (NK) cell activity, by 51Cr release assay. Treatment with M-CSF or WBH alone had a small effect on SFFU numbers but little or no effect on SFFV mRNA expression and SFFV-specific DNA. However, dramatically decreased levels of SFFU and SFFV mRNA and specific DNA fragments were observed in mice treated with M-CSF in combination with WBH, and NK cell activity was restored to normal. These results suggest the possibility that M-CSF may have a therapeutic effect in combination with WBH in the in vivo treatment of certain hematologic malignancies and/or retroviral infections. PMID- 1907927 TI - Non-lymphoid blast crisis of CML with rearrangement of immunoglobulin and T-cell receptor delta genes. AB - We report a patient with chronic myeloid leukaemia (Philadelphia-positive with M BCR rearrangement) in transformation whose blast cells had myelomonocytic morphology, absent terminal deoxynucleotidyl transferase expression and non lymphoid cell surface markers (CD10-, CD19-, CD33+, CD14+, CD11+). Leukaemia cell DNA showed rearrangement of both immunoglobulin heavy chain and T-cell receptor delta genes. Such rearrangements may be a feature of a small proportion of patients with non-lymphoid transformation of CML as they are in a minority of cases of de novo acute non-lymphoblastic leukaemia. PMID- 1907926 TI - Functional enhancement of intrastriatal dopamine-containing grafts by the co transplantation of sciatic nerve tissue in 6-hydroxydopamine-lesioned rats. AB - Peripheral nerve "bridges" demonstrate the ability to facilitate axonal growth and regenerate adult and fetal central nervous system tissue. The purpose of this study was to determine if co-grafted peripheral nerve tissue could enhance the ability of fetal dopamine (DA) cell transplants to reinnervate host striatum that had been denervated unilaterally. Male Fisher-344 rats were unilaterally lesioned with 6-hydroxydopamine to eliminate the nigrostriatal DA pathway. A total of 31 rats demonstrated a pattern of rotation indicative of a greater than 98% depletion in DA. Rats were kept as nongrafted controls (n = 6), grafted with sciatic nerve (PN) minces (n = 6), grafted with fetal ventral mesencephalon (VM; n = 10), or co-grafted with VM and PN minces (n = 9). All groups were then tested for changes in apomorphine-induced rotational behavior. The PN control group showed no significant differences in rotation when compared to pregrafting levels and to the lesioned nongrafted group. Both the VM-grafted group and the VM-PN co grafted group showed significant (P less than 0.01, one-way ANOVA) decreases in rotations beginning at 1.5 weeks postgrafting. There was a progressive decrease in rotations up to 12 weeks, the last test point examined. Interestingly, the co graft group revealed a significantly greater decrease in rotation (P less than 0.05) than the VM group beginning at 5 weeks and continuing out to the 12-week test point. Histological and immunocytochemical studies showed good survival of both PN and VM grafts. The augmented recovery could not be accounted for by increased DA cell survival or host brain DA reinnervation in the co-graft group. Taken together, these findings suggest that PN tissue enhances the ability of fetal VM grafts to reinnervate host brain. PMID- 1907928 TI - [Interferon-alpha and gamma product in peripheral blood of patients with thyroid diseases]. AB - To investigate the immunological process in various thyroid disease, we measured interferon-alpha, -gamma (IFN-alpha,-gamma, natural killer (NK) activity, and lymphocyte subsets in the peripheral blood of 27 patients with Basedow's disease (BD) (M:F = 9:18), 8 with Hashimoto's thyroiditis (HT) (2:6), 5 with idiopathic hypothyroidism (1HT) (1:4), and normal controls (C). IFN-alpha, -gamma levels were measured by bioassay with Dye-uptake method, and NK activity was measured by the LDH method. The mean +/- SD levels of IFN-gamma in BD, HT, IHT, and C (N = 217) were 173.9 +/- 88.0, 288.0 +/- 134.9, 120.4 +/- 38.0 and 173.9 +/- 88.01U/ml, respectively. The IFN-gamma level was higher in HT (p less than 0.05) than in controls, and lower in BD (p less than 0.02). Moreover, this IFN-gamma level did not correspond with the titers of thyroid hormones; TSH, anti-microsome antibody, and anti-TSH-receptor antibody in peripheral blood. However, IFN-alpha levels and NK activity in the patients of every group were similar to those in controls. The ratios of lymphocyte subsets of peripheral blood were measured by cytofluorometry with monoclonal antibodies. The mean +/- SD levels of T cells in BD, HT, IHT and C were 75.9 +/- 7.0, 83.4 +/- 7.2, 85.2 +/- 5.7, 82.3 +/- 5.8%, and those of B cells were 17.5 +/- 6.1, 10.9 +/- 4.2, 8.0 +/- 5.8, 10.9 +/- 5.0%, respectively. The ratio of T cells was higher in IHT (p less than 0.05) and lower in BD (p less than 0.01) than in controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1907929 TI - Quantitative determination of aflatoxin B1 in chick liver. AB - A method for the rapid and quantitative determination of aflatoxin B1 from small quantities of liver, around 1-2 g, is described. The extraction procedure involves acidification to pH 2 of the aqueous liver homogenates, extraction with chloroform: acetone and HPLC-fluorimetric detection after derivatization with trifluoroacetic acid. Quantitative recovery of aflatoxin B1 from chick liver was achieved and detection at levels of 0.2-1 ppb was proved feasible. The aflatoxin B1 concentration in chick liver after oral administration is also shown. PMID- 1907930 TI - Relationship between aldose reductase inhibiting activity and anti-cataract action of various non-steroidal anti-inflammatory drugs. PMID- 1907931 TI - Naproxen: an aldose reductase inhibitor and potential anti-cataract agent. PMID- 1907932 TI - Influence of metabolic disturbances of diabetes mellitus on serum CA 19-9 tumor marker. AB - CA 19-9 is a monoclonal antibody-defined tumor marker expressed by exocrine pancreas. It has been shown that exocrine atrophy was associated with deficiency. Hyperamylasemia has been described during ketoacidosis. Our study aimed at investigating the relationships between CA 19-9 and metabolic control of diabetes. Study was performed on 51 adult consecutive diabetic patients (21 type 1 and 30 type 2), with ketoacidosis or hyperosmolarity (group A, n = 15), poor glycaemic control (group B, n = 19), or good control (group C, n = 17). Serum CA 19-9 and metabolic parameters were evaluated on day 1 and day 30. Analysis of variance showed a very significant global difference between groups for CA 19-9 (p less than 0.0001); group A (66.1 +/- 11.4 u/ml) significantly differed from group B (36.4 +/- 4 u/ml) (p less than 0.01) and group C (22.4 +/- 2.8 u/ml) (p less than 0.001). Simple regression showed a significant correlation between CA 19-9 and fasting blood glucose (r = 0.6, p less than 0.001), plasma creatinine level (r = 0.37, p = 0.01), bicarbonate (r = 0.47, p = 0.001) and HbA 1c (r = 0.33, p = 0.032). The Ca 19-9 decrease on day 30 paralleled the improvement of glycaemic control. We conclude that CA 19-9 in diabetic patients is raised in acute metabolic situations and correlated very well with blood glucose concentration. A careful interpretation of this tumor marker assay is required when screening for pancreatic carcinoma among diabetic patients. CA 19-9 could be a useful and sensitive marker for the severity of exocrine damage and functional cellular disorders following metabolic disturbances in diabetes. PMID- 1907933 TI - Role of gastric mucosal blood flow in cytoprotection. AB - We compared the effects of graded doses of misoprostol (50-200 mg), omeprazole (12.5-50 mg), cimetidine (6.25-50 mg) and sucralfate (50-200 mg) on gastric mucosal blood flow as measured by laser Doppler flowmetry and gastric mucosal injury induced by ethanol. The results demonstrated that sucralfate, misoprostol and omeprazole, but not cimetidine, increased gastric mucosal blood flow in a dose-dependent manner and protected the mucosa against ethanol damage. The peak and summation blood flow were significantly greater with sucralfate than with misoprostol and omeprazole, but the degree of mucosal protection was similar. These results indicate that the increase in gastric mucosal blood flow, an action which is common to the three drugs, plays an important role in gastric mucosal protection, but other factors are also involved. PMID- 1907934 TI - Relationship between interferon-gamma, indoleamine 2,3-dioxygenase, and tryptophan catabolism. AB - Interferons have been shown to be potential anti-cancer agents and to inhibit tumor cell growth in culture. The in vivo mechanism of the anti-proliferative effect may be direct or indirect through the immune system; however, in vitro a primary mechanism of cytotoxicity is through the depletion of tryptophan. In particular, interferon-gamma (IFN-gamma) induces an enzyme of tryptophan catabolism, indoleamine 2,3-dioxygenase (IDO), which is responsible for conversion of tryptophan and other indole derivatives to kynurenine. The inhibitory effect of interferon on many intracellular parasites such as Toxoplasma gondii and Chlamydia trachomatis is by the same mechanism. Elevated kynurenine levels have been found in humans in a number of diseases and after interferon treatment, and the enzyme is induced in rodents after administration of interferon inducers, or influenza virus. IDO induction also occurs in vivo during rejection of allogeneic tumors, indicating a possible role for this enzyme in the tumor rejection process. The gene for IDO has been cloned and shown to be differentially regulated by IFN-alpha and IFN-gamma. IDO induction has been correlated with induction of GTP-cyclohydrolase, the key enzyme in pteridine biosynthesis. A direct role for IDO in pteridine synthesis has not been shown, and this parallel induction may reflect coordinate regulation of genes induced by IFN-gamma. A possible role for IDO in O2-radical scavenging and in inflammation is discussed. PMID- 1907936 TI - Molecular mechanisms of sleep-wake regulation: roles of prostaglandins D2 and E2. AB - Although sleep-wake cycles are repeated every day and night and almost one-third of our lifetime is spent sleeping, the molecular mechanisms of sleep-wake regulation have remained little understood. Recent experimental evidence indicates that prostaglandins (PG) D2 and E2 are probably two of the major endogenous sleep-regulating substances, one promoting sleep and the other wakefulness, in rats, dogs, rabbits, monkeys, and probably in humans as well. Preliminary evidence indicates that the sites of action of PGD2 and E2 are located in the sleep and wake centers in or near the preoptic area and posterior hypothalamus, respectively. PMID- 1907935 TI - Role of B cell antigen processing and presentation in the humoral immune response. AB - In the 25 years since it was first indicated that lymphocyte subpopulations must interact during the generation of a humoral immune response, there has been an explosion of data on the molecular mechanism of this interaction. It has been demonstrated that T cells recognize a processed antigen fragment presented by a major histocompatibility complex molecule on the surface of an antigen-presenting cell. The minimal peptides required for T cell recognition of several proteins have been determined, the molecular genetics of many of the cell surface molecules involved have been defined, and the three-dimensional structure of the T cell receptor and the major histocompatibility antigens have been deduced. Several cell types have been found to act as antigen-presenting cells, although the roles of these populations in vivo remain unclear. However, it is clear that there must be a physical interaction between a B cell and a T cell before the B cell can respond to a T-dependent antigen. This interaction requires processing and presentation of the antigen by the B cell. Therefore this review focuses on antigen processing and presentation by resting B cells, one of the key steps in initiation of a humoral immune response. PMID- 1907937 TI - [Electropharmacological test with class-I C drugs in paroxysmal supraventricular re-entrant tachycardia: is a negative result with a drug predictive of the ineffectiveness of other drugs of the same class?]. AB - Propafenone and flecainide, both I C class drugs, are first choice in the treatment of paroxysmal supraventricular reciprocating tachycardia. The aim of this study was to check whether a negative or paradoxical electropharmacological test with one of the two drugs was predictive of an equally negative or paradoxical test with the other drug. Thirty patients with disabling paroxysmal supraventricular reciprocating tachycardia, 16 M, 14 F, mean age 30.6 +/- 16 years, were studied with serial electropharmacological tests using esophageal approach. The reentry circuit was sustained by an anomalous pathway in 25 patients (83.5%) whereas it was idionodal in the other 5 (16.5%). Propafenone was tested in 13 patients (43.5%, group A) after flecainide had resulted negative or paradoxical in the first test. In 17 patients (56.5%, group B) flecainide was tested after propafenone had resulted negative or paradoxical. The second drug tested was also ineffective in 14 of the 30 patients (group A + group B) while it had positive results in 16 patients. Specifically, propafenone was positive in 6 of the 13 patients (group A) in whom flecainide had been negative, and flecainide was positive in 10 of the 17 patients (group B) with acute negative or paradoxical propafenone test. These "acute" results were confirmed in steady state with esophageal study and in the follow-up (21.9 +/- 9.3 months). CONCLUSIONS: 53.5% of the patients who are "non responders" to the electropharmacological test with one of the two drugs (propafenone or flecainide) may be "responders" to the other drug. Thus the ineffectiveness of one of the two drugs is not predictive of ineffectiveness of the other. PMID- 1907938 TI - [Continuous pulsatile subcutaneous gonadotropin stimulation in polycystic ovary syndrome: a therapeutic alternative]. AB - In order to improve the ovarian response to exogenous gonadotropins and to reduce the risk of the ovarian hyperstimulation syndrome and of multiple pregnancies, human menopausal gonadotropin (hMG) was administered by continuous pulsatile subcutaneous (s.c.) infusion via a portable pump. The effectiveness of pulsatile hMG treatment was first demonstrated in a control group comprising 7 females with regular ovulatory cycles, who underwent gonadotropin ovarian superovulation and subsequent IVF/GIFT procedures for tubal or male factor. All pulsatile s.c. hMG cycles were ovulatory and one clinical pregnancy was achieved. In this group, ovarian response was similar following intramuscular (i.m.) and pulsatile s.c. hMG therapy, with a marked reduction of preovulatory serum levels of oestradiol in the pulsatile s.c. hMG cycles. In a prospective study, 11 patients with overt polycystic ovary syndrome (PCO) who failed to ovulate in response to clomiphene, received i.m. hMG ovarian superovulation treatment in 19 cycles and pulsatile s.c. hMG in 21 cycles. Following i.m. hMG treatment, only 10 cycles were ovulatory; 7 cycles had to be cancelled for impending ovarian hyperstimulation syndrome. Following pulsatile s.c. hMG treatment, 15 cycles were ovulatory, only 3 treatment cycles had to be disrupted for multifollicular ovarian response. Both modes of treatment were similar in terms of requirement of hMG ampoules, number of preovulatory follicles, preovulatory serum levels of oestradiol and duration of the preovulatory oestradiol rise. The total duration of hMG treatment was significantly increased following pulsatile s.c. hMG. It is concluded, that in overt PCO syndrome, continuous pulsatile s.c. administration of hMG is an effective method to induce follicular maturation and to achieve ovulations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1907939 TI - Effects of vanadate in testicular capsule of the rat. AB - 1. The effects of sodium orthovanadate (vanadate. 10(-5) to 3 x 10(-4) M) on testicular capsule of the rat, and the modifications of these effects by the calcium chelator EGTA (2mM), the calcium entry blockers verapamil (5 X 10(-5) M), nifedipine (10(-5 M) and diltiazem (5 x 10(-5) M), the (Na+ + K+)-ATPase inhibitor ouabain, the Na+/Ca2+ exchange inhibitor amiloride, and the calmodulin antagonists trifluoperazine (10(-4) M) and W-7 (5 x 10(-5) M) have been studied. 2. Vanadate induced contraction of the rat testicular capsule in a dose-dependent way (ED50: 82.8 +/- 7.4 x 10(-6) M). 3. The contraction induced by vanadate (3 and 30 x 10(-5) M) were abolished by EGTA and not modified by verapamil, nifedipine, flunarizine or diltiazem. 4. Amiloride (1 and 5 x 10(-5) M), but not ouabain (5 x 10(-5) and 10(-4) M), inhibit in a dose-dependent way the contraction induced by two doses of vanadate (3 and 30 x 10(-5) M). 5. Trifluoperazine and W-7 significantly inhibit the contraction of testicular capsule to 3 and 30 x 10(-5) M vanadate. PMID- 1907940 TI - Expression of a retinoic acid response element-hsplacZ transgene defines specific domains of transcriptional activity during mouse embryogenesis. AB - Treatment with retinoic acid (RA) is known to produce complex teratogenic effects in vertebrates, and its presence in the developing embryo as an endogenous substance has led to the suggestion that RA might be a natural morphogenetic agent. Although our understanding of the molecular mechanism of RA action has improved considerably with the identification of nuclear receptors for RA (RARs) and RA-responsive genes, the exact relationship between the proposed morphogenetic activity of RA and its teratogenic effects remains to be characterized. Here, we show that a RA response element (RARE) present in the RAR beta gene can direct specific spatial and temporal expression of an hsplacZ transgene during mouse embryogenesis. In the early embryo, the transgene is expressed in a specific anterior-posterior domain that is completely obliterated by treatment of pregnant mice with teratogenic doses of RA. The expression of the transgene becomes more restricted as organogenesis progresses and mimics closely the reported expression of the RAR beta gene. These results suggest that, in vivo, some of the morphogenetic effects of RA could be mediated through localized transcriptional activity controlled by the various RARs. The specific pattern of expression of the RAREhsplacZ transgene does not correlate with the proposed sites of action of RA as defined by its teratogenic effects but does support a role for RA in early anterior-posterior patterning along the body axis. PMID- 1907941 TI - The rel-associated pp40 protein prevents DNA binding of Rel and NF-kappa B: relationship with I kappa B beta and regulation by phosphorylation. AB - The product of proto-oncogene Rel associates with a number of cellular proteins. We have studied the effect of one of them, a phosphoprotein of 40 kD (pp40), on the DNA-binding activity of the Rel protein. We demonstrate that purified pp40 not only inhibits the binding of Rel, but also NF-kappa B (p50-p65) heterocomplex to DNA. Additionally, I kappa B beta, but not I kappa B alpha, also prevented the binding of Rel to the kappa B site. I kappa B beta and pp40 are related proteins because (1) they share a number of common tryptic peptides, (2) their inhibitory effect on DNA binding can be abolished by preincubation with pp40-specific antiserum, and (3) labeled I kappa B beta can be immunoprecipitated with pp40 antibodies. pp40 is part of the Rel complex present in the cytoplasm and nuclear extracts of WEHI-231 cells. The activity of pp40 to inhibit the DNA binding of Rel and NF-kappa B is modulated by phosphorylation. PMID- 1907943 TI - [Indication for, technique and results of reconstruction of traumatic defects of the bony orbital floor]. PMID- 1907942 TI - [Primary correction of orbital fractures using PDS-foil]. PMID- 1907944 TI - [Long-term results following orbital comminuted fractures with special reference of orbital floor reconstruction using an absorbable PDS-plate]. PMID- 1907945 TI - [Animal experiments for the determination of in-vivo absorption of PDS osteosynthesis material]. PMID- 1907946 TI - Prostate--a novel target for evaluation of FSH modulating peptides. AB - Effects of prostatic inhibin peptide and its synthetic fragments on FSH biosynthesis by the human pituitary and prostate, were examined in vitro. The results showed that FSH biosynthesis by prostatic tissue is modulated by these peptides in a similar fashion to that observed at the pituitary level. PMID- 1907947 TI - Effect of chromium on growth of Pseudomonas aeruginosa. AB - Tolerance level to trivalent chromium-Cr(salen)(H2O)2+ and hexavalent chromium K2Cr2O7 was assessed in P. aeruginosa isolated from tannery effluent soil. It could tolerate 80 and 100 ppm in liquid cultures and up to 100 and 200 ppm in plate count agar in the presence of trivalent and hexavalent chromium respectively. Unadapted cells took a longer time to grow than adapted cells in the presence of K2Cr2O7. Chromium influenced the cellular contents, morphology and respiration of P. aeruginosa. The chosen trivalent salt of chromium was more toxic than the hexavalent one. PMID- 1907948 TI - Morphological evidence for two types of idiopathic 'Sertoli-cell-only' syndrome. AB - Biopsies of testicular specimens taken from 41 patients that were diagnosed as having idiopathic Sertoli-cell-only syndrome were classified into two types, A and B, on the basis of histological and immunohistochemical findings. Thirty eight specimens that were classified as type A exhibited seminiferous tubules of small diameter and with tubular wall hyalinization, but containing normal adult type Sertoli cells. The other three specimens that were classified as type B showed no seminiferous tubular wall hyalinization, and their Sertoli cells had vimentin distribution localized in the subnuclear cytoplasm and had a pseudostratified lining, features resembling the appearance of fetal Sertoli cells. In one patient with a seminoma, a comparative study of the same testis prior to and post-irradiation was undertaken. Judging from this, postpubertal depletion of the germ cell population was considered to be responsible for the tubular atrophy observed in type A. Type B testes, though small in number, were characterized by a morphology distinct from the type A, but their pathogenesis remains unknown. PMID- 1907949 TI - [The HBsAG negative, anti-HBc/anti-HBS positive patient]. PMID- 1907950 TI - Therapeutic response of herpes simplex virus-induced corneal edema to trifluridine in combination with immunosuppressive agents. AB - Herpetic stromal disease often is treated with combinations of antiviral agents and corticosteroids. The addition of steroids to the antiviral treatment regimen frequently increases the efficacy of therapy in patients; however, many complications may arise as a result of corticosteroid therapy. Using a rabbit model, the effects of trifluridine (F3TdR) on corneal edema and stromal disease were examined when combined with each of three immunosuppressive agents. The therapeutic response was evaluated by classifying eyes as either responsive or unresponsive based on the maximum corneal thickness attained during therapy. The data indicate that about 56% of the eyes responded to therapy with 1% F3TdR alone even when therapy was initiated after signs of stromal inflammation had begun to appear and epithelial disease was resolving. Combination of F3TdR with 0.125% prednisolone acetate significantly increased the proportion of responsive eyes to about 78%. Therapy with F3TdR combined with topical 5% cyclosporine A was no better than F3TdR alone, and combination with 0.2% deoxycoformycin and 0.4% 2' deoxyadenosine significantly decreased the proportion of responsive eyes. These data further document that the responses of stromal disease to therapy must be evaluated on an eye-by-eye basis because the distribution of the data may not be Gaussian in nature. Eyes with corneal edema and stromal disease induced by herpes simplex viral (HSV) infection may respond to therapy with antiviral agents alone, but others require steroid. Still others do not respond to combined therapy. Combining the responses of all eyes in a given treatment group to obtain a "population mean" may be misleading.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1907951 TI - The Christine Busalacchi case. PMID- 1907952 TI - Carcinoma of the tonsillar fossa: a nonrandomized comparison of irradiation alone or combined with surgery: long-term results. AB - The results of therapy are reported in 296 patients with histologically proven epidermoid carcinoma of the tonsillar fossa; 127 were treated with irradiation alone (5,500 to 7,000 cGy), 133 with preoperative radiotherapy (2,000 to 3,000 cGy) or were initially planned for preoperative irradiation but treated with radiotherapy alone, and 36 with postoperative irradiation (5,000 to 6,000 cGy). The operation in all but 4 patients consisted of an en bloc radical tonsillectomy with ipsilateral lymph node dissection. Actuarial 5-year no evidence of disease (NED) was as follows: survival rates for patients with T1 tumors, 76%; T2, 54%; T3, 45%; and T4, 20%. Patients with no cervical lymphadenopathy or with a small metastatic lymph node (N1) had better relapse-free survival (60% to 70% at 5 years) than those with large or fixed lymph nodes (30% to 40%). Primary tumor recurrence rate in the T1-T2 groups was about 20% in patients treated with irradiation and surgery and 30% for those treated with irradiation alone (difference not statistically significant), 30% in patients with stage T3 lesions in all treatment groups, and 33% in patients with T4 disease treated with surgery and postoperative irradiation compared to 52% with irradiation alone (p = 0.03). The overall recurrence rate in the neck was about 20% for the N0 patients, 25% for N1, and 30% for those with N2 and N3 cervical lymph nodes in the 4 treatment groups. The incidence of contralateral neck recurrences was about 8% with the various treatment modalities.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1907953 TI - Swallowing recovery following anterior tongue and floor of mouth surgery. AB - Videofluoroscopic and clinical data are presented for postsurgical recovery of tongue and hyoid activity during swallowing. Comparison is made to normal controls. Postsurgery, but prior to radiotherapy, both the lingual propulsive gesture and hyoid velocity were slower than normal. These features of the swallow had returned to the normal range following radiotherapy. The general sequencing of swallowing events, and the relationship of the end of the tongue propulsion to anterior hyoid motion were normal in those patients able to swallow. In this patient group, postsurgical radiotherapy did not prevent continued recovery of swallowing function sufficient for oral nutrition. PMID- 1907954 TI - A high activity carbonic anhydrase isoenzyme (CA II) is present in mammalian spermatozoa. AB - Human and rat spermatozoa were stained for different carbonic anhydrase (CA) isoenzymes using specific antisera to human CA I, II and VI in conjunction with the immunofluorescence technique. The spermatozoa of both species were found to contain only CA II, which was located principally in the postacrosomal region of the human spermatozoa and in the acrosomal cap region of the rat spermatozoa. The presence of CA II could be confirmed by immunoblotting, which revealed a 29 K polypeptide in both the human and rat spermatozoa. No CA I or VI-specific fluorescence could be detected in the spermatozoa of either species. The immunoblottings were also negative. The results show mammalian spermatozoa to contain the high activity carbonic anhydrase isoenzyme II. Its presence is probably linked to hydration of CO2 produced by active energy metabolism and thereby to the maintaining of an adequate intraspermatozoal bicarbonate concentration as required for the maintenance of sperm motility. PMID- 1907955 TI - Selective, quantitative detection of cadmium and/or zinc by use of BTAN (2 aminobenzothiazolylazo-beta-naphthol). AB - BTAN (Sumi Y et al. (1982) Histochemistry 73:481) was investigated as a histochemical Cd/Zn chelator. Cd-BTAN exhibits a main peak about 635 nm, while Zn BTAN exhibits a main peak about 644 nm. The isobestic wavelength for Cd-BTAN and Zn-BTAN is 638 nm. The microscopical detection limit for Cd is about 25 amol/microns 2, and for Zn about 5 amol/microns 2. The relation between metal and bound chelator is fairly linear at a BTAN concentration more than 10-fold the metal concentration. Histochemical localization was fair to good, with a crystal size of up to 0.2-0.3 micron. The chelate was unaffected by hydrophilic and largely also by hydrophobic mounting media. The original staining procedure proved erratic and was modified. Posttreatment with oxine to selectively demonstrate Cd in the presence of Zn (Sumi Y et al. 1982) seriously reduced the staining intensity. Post-treatment for 8-15 min with HCl, 0.5 mol/l, in 50% ethanol removed Cd-BTAN completely with little reduction of Zn staining intensity, even from sites with 5x as much Cd as Zn. It is concluded that BTAN permits direct quantitative detection of (Zn + Cd). Provided certain precautions are taken quantitative detection of Zn and quantitation of Cd in mixed Zn/Cd sites is possible by microphotometry of the stained section before and after differentiation for 8-15 min with the HCl/50% ethanol medium. PMID- 1907956 TI - Ultrastructural demonstration of neurohaemal contacts in the internal zone of the median eminence of the Mongolian gerbil (Meriones unguiculatus): correlation with synaptophysin immunohistochemistry. AB - Electron microscopy of the median eminence (ME) of the Mongolian gerbil (Meriones unguiculatus) revealed that, unlike most other mammalian species, abundant neurohaemal contacts were present not only in the external zone (EZ), but also in the internal zone (IZ) up to the subependymal layer. In the IZ, nerve terminals with dense core vesicles and/or small clear vesicles abutted on the outer basal lamina of the perivascular space of portal capillaries, alternating with tanycyte processes. In addition to these neurohaemal contacts, several layers of vesicle filled varicosities surrounded the portal vasculature. An analysis of serial thin sections showed that the latter varicosities could also reach the perivascular basal lamina or contact it through small extensions in other planes of section. Apparently at least some of the nerve terminals making neurohaemal contacts were en passant in nature. A correlative investigation of synaptophysin (a major integral membrane protein of small synaptic vesicles) immunoreactivity at the light microscopical level demonstrated a conspicuously dense immunostaining around portal capillaries in both EZ and IZ of the proximal and distal ME (neural stalk). Since this perivascular accumulation of immunoreactivity coincides precisely with the ultrastructural accumulation of vesicle-filled axons which establish numerous neurohaemal contacts, it is concluded that this pattern of synaptophysin immunostaining indicates sites of neurohaemal contacts at the light microscopical level. During postnatal development, the perivascular concentration of synaptophysin immunoreactivity in the IZ appeared concomitantly with the early postnatal expansion of long portal capillary loops into the IZ.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1907957 TI - Variables associated with the development of complications from radiosurgery of intracranial tumors. AB - Between 5/21/86 and 11/1/89, we treated 64 recurrent or inoperable intracranial tumors in 60 patients (40 primary, 24 metastatic) with stereotactic radiosurgery using a modified 6 MeV linear accelerator at the Joint Center for Radiation Therapy. Patients were followed until death or 1/1/90. The median follow-up was 8 months (2-43 months). Fourteen patients experienced complications from 12 hours to 7 months (median 3 months, but only two patients more than 4 months) following radiosurgery. To determine variables related to complication, we calculated integral dose-volume histograms for 61/64 lesions and the surrounding CT-defined normal tissue. We excluded 16 lesions in 15 patients for follow-up less than 4 months (12 patients) or insufficient treatment information (3 patients). The variables for which higher values were associated with significantly more toxicity in a univariate score test were: a) tumor dose inhomogeneity (p less than 0.00001), b) maximum tumor dose (p = 0.00002), c) number of isocenters (p = 0.00002), d) maximum normal tissue dose (p = 0.00005) and e) tumor volume (p = 0.0001). These variables were all highly correlated with tumor dose inhomogeneity (coefficients of rank correlation 0.75-0.81). Tumor dose inhomogeneity had a much higher loglikelihood in a logistic model than any other single variable and a higher loglikelihood than any other two variables combined. None of the 21 patients with metastatic lesions experienced a complication. When we excluded the metastatic lesions, the above five variables remained significant in univariate tests. The mean tumor dose, number of treatment arcs, total degrees of arc, tumor location, previous radiotherapy, tumor geometry, pretreatment performance status, collimator size, and age were not significantly associated with toxicity. We conclude that radiosurgery of intracranial tumors is associated with a low risk of complications for lesions less than 10cc treated with a single isocenter to maximum tumor doses less than 25 Gy with tumor dose inhomogeneity less than 10 Gy, but that treatment of larger lesions will require new treatment strategies which reduce the tumor dose inhomogeneity associated with multiple isocenter treatments. PMID- 1907958 TI - Long-term follow-up of radiotherapy for pituitary adenoma: the absence of late recurrence after greater than or equal to 4500 cGy. AB - Recent literature has suggested that late recurrence of pituitary adenoma after radiotherapy is common. We hypothesized that late failures might be a result of inadequate dose (less than 4500 cGy). To investigate, we analyzed 105 patients treated at our institution between 1965 and 1986 (analysis, 2/89). The minimum observation time was greater than or equal to 5 years in 58% and greater than or equal to 10 years in 30% of the patients. All patients received megavoltage radiotherapy (range, 4200-5500 cGy; mean, 4821 cGy) at a mean dose per fraction of 172 cGy; 100 patients received greater than or equal to 4500 cGy tumor dose. Twenty-nine patients received radiotherapy alone, and 76 had postoperative radiotherapy after frontal craniotomy (20 patients) or transsphenoidal hypophysectomy (56 patients). At presentation, 71% of patients had extrasellar disease, 57% had visual field deficits, and 50% had endocrinopathy. Of patients treated postoperatively, 74% had gross residual disease. Four local failures occurred at 13, 16, 57, and 64 months after postoperative radiotherapy, all within the irradiated volume (tumor doses of 4700, 4715, 5000, and 5100 cGy). All four patients had presented with moderate to extensive extrasellar disease with visual field defects. Two of the four remain free of second recurrence at 7 and 13 years after salvage transsphenoidal hypophysectomy. The local control rate with radiotherapy (product-limit method) at 10 years was 100% in the radiotherapy alone group and 92% in the postoperative radiotherapy group (95% for all patients). To prevent bias, seven patients who received bromocriptine, none of whom demonstrated a recurrence, were censored from the local control analysis at the initiation of the drug. No patient in this study suffered recurrence greater than 64 months after radiotherapy, with 31 patients (none with bromocriptine) observed 10 to 21 years. We conclude that treatment of pituitary adenoma with greater than or equal to 4500 cGy in 25 fractions can result in a high (greater than or equal to 90%) probability of stable long-term control. PMID- 1907959 TI - Chiasmal gliomas: results of irradiation management in 57 patients and review of literature. AB - Fifty-seven patients with optic gliomas, treated by megavoltage radiotherapy between May 1970 and March 1986, are retrospectively analyzed. The mean follow-up was 7.5 years (2.5-16.5). At presentation, 46% were under 10 years old, 40% had neurofibromatosis, and 51% had neurological and/or endocrinological signs. Twenty one tumors (37%) were confined to the optic chiasm, and 36 tumors (63%) extended to the hypothalamus, the posterior optic tract, or the adjacent brain. Two among the 16 biopsy-proven tumors were high grade gliomas. Delivered tumor doses were 40 to 60 Gy in 5 to 7 weeks. Forty-nine patients were alive (five with tumor evolution) and eight had died (five from the tumor, one from cerebrovascular complication, two from intercurrent disease). Overall actuarial survival was 83.5% at 5 and 10 years. Control of the disease in 53 evaluables patients was: complete response in 8 (15%), partial response in 25 (46%), and no progression in 12 (22%). Progressive disease was observed in three patients and signs evocative of recurrence in five others. Stabilization of visual impairment or improvement of vision was recorded in 93% of patients who were evaluable. A critical review of the literature is presented and complications discussed. Radiotherapy seems thus effective in chiasmal gliomas and must be delivered in cases of rapidly developing symptoms visual, neurological, or endocrine. PMID- 1907960 TI - Treatment planning for stereotactic radiosurgery of intra-cranial lesions. AB - Stereotactic radiosurgery of intra-cranial lesions is a treatment modality where a well defined target volume receives a high radiation dose in a single treatment. Our technique delivers this dose using a set of non-coplanar arcs and small circular collimators. We use a standard linear accelerator in our treatments, and the adjustable treatment parameters are: isocenter location, gantry arc rotation interval, couch angle, collimator field size, and dose. The treatment planning phase of the treatment determines these parameters such that the target volume is sufficiently irradiated, and dose to surrounding healthy tissue and critical, dose-limiting structures is minimized. The attachment of a BRW localizing frame to the patient's cranium combined with CT imaging (and optionally MRI or angiography) provides the required accuracy for localizing individual structures in the treatment volume. The treatment is fundamentally 3 dimensional and requires a volumetric assessment of the treatment plan. The selection of treatment arcs relies primarily on geometric constraints and the beam's eye view concept to avoid irradiating critical structures. The assessment of a treatment plan involves isodose distributions throughout the volume and integral dose-volume histograms. We present the essential concepts of our treatment planning approach, and illustrate these in three clinical cases. PMID- 1907961 TI - An anterior appositional electron field technique with a hanging lens block in orbital radiotherapy: a dosimetric study. AB - A technique for orbital radiotherapy is presented consisting of an anterior, appositional electron beam with a hanging lens block. The beam was modified by introducing two 1.6 mm thick plastic spoilers, at about 3 cm and 15 cm from the lens, to boost in-scattering of electrons under the block. The 9 mm diameter, 2 cm long stainless steel cylindrical block was suspended 0.5-1.0 cm above the eye. We performed film, TLD (Thermo Luminescent Dosimetry), and diode dosimetry to determine the dose fill-in behind the lens. The introduction of the spoilers dramatically changed the dose distribution. The maximum dose under the block increased from 66% to 85% of the open field dose. Moreover, the dose to the posterior surface of the globe directly underneath the block, at a depth of 3 cm, increased from 48% to 76% of maximum dose, while the dose to the lens was still below 20%. This is a simple and easily reproducible treatment and is an improvement on a previously described technique. The dose distribution is adequate for cases where the target volume surrounds and is posterior to the globe. PMID- 1907962 TI - Optimal treatment for salivary gland tumors. PMID- 1907963 TI - Double-blind comparison of bupropion and fluoxetine in depressed outpatients. AB - BACKGROUND: This study was undertaken to compare the efficacy and safety of bupropion and fluoxetine. METHOD: Moderately to severely depressed outpatients who fulfilled the DSM-III-R criteria for nonpsychotic major depressive disorder and had a score of 20 or more on the Hamilton Rating Scale for Depression (21 item) participated in this two-center study. Following a 1-week placebo phase, patients were randomly assigned to receive either bupropion or fluoxetine for 6 weeks of double-blind treatment. Weekly efficacy assessments included Hamilton Rating Scale for Depression, Hamilton Rating Scale for Anxiety, Clinical Global Impressions-Severity, and Clinical Global Impressions-Improvement. Vital signs and adverse experiences were also assessed weekly. RESULTS: A total of 61 patients were randomly assigned to receive bupropion (225-450 mg/day) and 62 were randomly assigned to receive fluoxetine (20-80 mg/day). The mean daily dose at the end of the study was 382 mg/day for the bupropion treatment group and 38 mg/day for the fluoxetine treatment group. There were no statistically significant differences between treatments on any of the efficacy variables. On the basis of a 50% or greater reduction in the HAM-D scores, 63% (N = 37) of the bupropion-treated and 58% (N = 35) of the fluoxetine-treated patients were categorized as responders, and on the basis of CGI scores, 68% (N = 40) of the bupropion-treated and 58% (N = 35) of the fluoxetine-treated patients were rated as much or very much improved. HAM-A scores decreased by 59% for both treatment groups. The incidence of treatment-emergent adverse events was low with no statistically significant differences between treatments. Twenty-six percent (N = 16) of the bupropion-treated and 29% (N = 18) of the fluoxetine-treated patients prematurely discontinued treatment. CONCLUSION: Both bupropion and fluoxetine demonstrated similar efficacy in relieving depression and accompanying symptoms of anxiety, and both exhibited a similar, favorable safety profile. PMID- 1907964 TI - The use of selegiline in Alzheimer's patients with behavior problems. AB - BACKGROUND: Currently there is no regimen for managing the inappropriate behavior seen in Alzheimer's disease that does not cause significant patient sedation. Preliminary evidence suggests selegiline may be effective in behavioral modification without the adverse effects observed with other regimens. The purpose of this study was to document the efficacy of selegiline in Alzheimer's patients with behavior problems. METHOD: Eight Alzheimer's patients (6 women and 2 men) ranging in age from 50 to 82 years (mean +/- SD = 74.0 +/- 10.5) were enrolled in this single-blind study. Patients received selegiline 10 mg each day for 8 weeks. Prior to drug administration and at the end of Weeks 1, 2, 4, 6, and 8, patients were evaluated for behavior (BEHAVEAD), cognitive function (Mini Mental State Examination), and caregiver stress (Caregiver Burden Scale). RESULTS: Of eight enrolled patients, five were available for analysis. No statistically significant differences were found between mean baseline and mean 8 week scores for any of the three tests. However, clinical significance was noted by improvement in cognition (orientation and recall), caregiver stress, and behavior. Behavior was noted to improve in the areas of paranoid and delusional ideation, hallucinations, activity disturbances, anxiety, and phobias. CONCLUSION: These data suggest that some Alzheimer's patients with behavior problems may benefit from selegiline therapy. PMID- 1907965 TI - Tinnitus related to bupropion treatment. PMID- 1907966 TI - The amino acid sequences of two 13 kDa polypeptides and partial amino acid sequence of 30 kDa polypeptide of complex I from bovine heart mitochondria: possible location of iron-sulfur clusters. AB - Mitochondrial NADH:ubiquinone oxidoreductase (complex I) is the most complicated system in the respiratory chain. It consists of many subunits, some of which hold iron-sulfur clusters, but structural information is still limited. The amino acid sequences of two 13 kDa polypeptides, 13 kDa-A and 13 kDa-B polypeptides, of iron sulfur protein fraction (IP) of bovine heart mitochondrial complex I were determined by a combination of protease digestion, Edman degradation, and carboxypeptidase digestion. The 13 kDa-A polypeptide was composed of 96 amino acids with a molecular weight of 10,536. The 13 kDa-B polypeptide consisted of 114 amino acids and had an acetylated amino terminus. The molecular weight of this protein was calculated to be 13,130 including the acetyl group. These proteins had no obvious sequence similarity to other known proteins. The partial amino acid sequence of 30 kDa-B polypeptide of IP was also determined to reveal a characteristic arrangement of cysteine residues that could be involved in iron sulfur cluster formation. PMID- 1907967 TI - Drug-induction decreases the mobility of cytochrome P-450 in rat liver microsomes: protein rotation study. AB - Effect of drug-induction on the rotation of cytochrome P-450 and on lipid fluidity in rat liver microsomes was examined. Rotational diffusion of cytochrome P-450 was examined by observing the decay of absorption anisotropy, r(t), after photolysis of the heme.CO complex by a vertically polarized laser flash. Analysis of r(t) was based on a "rotation-about-membrane normal" model. Microsomal lipid fluidity was measured by observing fluorescence anisotropy of DPH incorporated in the lipid bilayer. The absorption anisotropy decayed within 2 ms to a time independent value. Rotational diffusion of cytochrome P-450 was dependent on the drug-induction with PB, MC, and PCB when compared with non-induced CON microsomes. The observed values for the normalized time-independent anisotropy r(infinity)/r(0) are r(infinity)/r(0) = 0.41 (CON-microsomes), 0.54 (PB microsomes), 0.52 (MC-microsomes), and 0.57 (PCB-microsomes). The average rotational relaxation time phi = 580-690 microseconds was almost unchanged over all microsomes presently examined. A significantly high value of r(infinity)/r(0) = 0.41-0.57 implies the co-existence of mobile and immobile populations of cytochrome P-450. Based on the assumption that the heme tilts about 55 degrees from the membrane plane for all species of P-450s besides P-450PB, 59% (CON microsomes), 46% (PB-microsomes), 48% (MC-microsomes), and 43% (PCB-microsomes), respectively, of the cytochrome P-450 in microsomes is calculated to be mobile. Upon drug-induction the microsomal membrane was fluidized to some extent as judged by the steady-state fluorescence anisotropy of 0.156 for CON-microsomes and 0.139-0.148 for drug-induced microsomes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1907968 TI - Inhibition of homoserine dehydrogenase I by L-serine in Escherichia coli. AB - We have reported that a major cause of growth inhibition of Escherichia coli by L serine is its inhibition of homoserine dehydrogenase I (HDH I), which is involved in the biosyntheses of threonine and isoleucine [Hama, H., Sumita, Y., Kakutani, Y., Tsuda, M., & Tsuchiya, T. (1990) Biochem. Biophys. Res. Commun. 168, 1211 1216]. However, Patte et al. reported that L-serine does not inhibit HDH I [Patte, J.-C., Truffa-Bachi, P., & Cohen, G.N. (1966) Biochim. Biophys. Acta 128, 426-439]. In studies on the reason for these discrepant results, we found that the concentration of K+ and the pH in the assay mixture strongly influenced the inhibitory effect of L-serine. L-Serine strongly inhibited the HDH I activities in both the forward and reverse reactions between aspartate semialdehyde and homoserine at a physiological K+ concentration (100 to 200 mM) and physiological pH (7.5) for E. coli cells. On the other hand, two well-known inhibitors of HDH I, L-threonine and L-cysteine, strongly inhibited the activity regardless of the K+ concentration and pH. PMID- 1907969 TI - Fluorescence quenching studies on the characterization of energy generated at the NADH:quinone oxidoreductase and quinol oxidase segments of marine bacteria. AB - Generation of membrane potential (inside-positive) and delta pH (inside-acidic) at two kinds of NADH:quinone oxidoreductase segments, the Na(+)-motive segment and another segment, of Vibrio alginolyticus was examined by monitoring the quenching of fluorescence of oxonol V and that of quinacrine, respectively, with inside-out membrane vesicles. Transient generation of membrane potential at the segment occurred when ubiquinone-1 was added in the presence of KCN and NADH. The membrane potential was resistant to a proton conductor, carbonylcyanide m chlorophenylhydrazone, indicating that the membrane potential was generated specifically at the Na(+)-motive segment. On the other hand, neither membrane potential nor delta pH was generated at another segment. The Na(+)-motive segment did not generate delta pH, indicating that only Na+ is extruded at this segment. Furthermore, generation of membrane potential and delta pH at the NADH:quinone oxidoreductase segment of V. anguillarum was examined by using the fluorescence quenching technique. This segment of the bacterium was also found to generate delta psi by the extrusion of Na+ but not H+. These results revealed that the fluorescence quenching technique is useful for the rapid identification and characterization of the respiratory segment involved in Na+ translocation. PMID- 1907971 TI - Definition of a consensus sequence for peptide substrate recognition by p44mpk, the meiosis-activated myelin basic protein kinase. AB - Synthetic peptides have been used to define the consensus amino acid sequence for substrate recognition by the meiosis-activated myelin basic protein (MBP) kinase (p44mpk), which was purified from maturing sea star oocytes. This protein kinase shares many properties with the mitogen-activated microtubule-associated protein 2 kinase (p42mapk) in vertebrates. Recently, Thr-97 in the tryptic fragment KNIVTPRTPPPSQGK of bovine MBP was identified as the major site of phosphorylation by p44mpk (Sanghera, J. S., Aebersold, R., Morrison, H. D., Bures, E. J., and Pelech, S. L. (1990) FEBS Lett. 273, 223-226). Synthetic peptides modeled after this sequence revealed that the presence of a proline residue C-terminal (+1 position) to the phosphorylatable threonine (or serine) residue was critical for recognition by p44mpk. Although not essential, a proline residue located at the 2 position enhanced the Vmax of peptide phosphorylation. Basic, acidic, and non polar residues were equally tolerated at the -1 position. The presence of an amino acid residue at position -3 also increased peptide phosphorylation. Thus, the optimum consensus sequence for phosphorylation by p44mpk was defined as Pro-X (Ser/Thr)-Pro, where X is a variable amino acid residue, but ideally not a Pro. Peptides that included this sequence were phosphorylated by p44mpk with Vmax values approaching 1 mumol.min-1.mg-1 and with apparent Km values of approximately 1 mM). Pseudosubstrate peptides in which the phosphorylatable residue was replaced by valine or alanine were weak inhibitors of p44mpk (apparent Ki values of approximately 3 mM). Over 40 distinct protein kinases contain Pro-X-(Ser/Thr)-Pro sequences including the human receptors for insulin and epidermal growth factor, and kinases encoded by the human proto-oncogenes abl, neu, and raf-1, and Schizosaccharomyces pombe cell cycle control genes ran-1 and wee-1. Multiple putative sites were also identified in rat microtubule associated protein-2, human retinoblastoma protein, human tau protein, and Drosophila myb protein and RNA polymerase II. PMID- 1907970 TI - Characterization of threonine transport into a kidney epithelial cell line (BSC 1). Evidence for the presence of Na(+)-independent system asc [corrected]. AB - The transport routes for threonine in a primate kidney epithelial cell line (BSC 1) grown as monolayer in continuous cell culture were studied. We discovered at least four different transport systems for threonine uptake. The Na(+)-dependent route shows biphasic kinetics with a low and high affinity parameter. The apparent kinetic constants for Km1 and Km2 were 0.3 and 36 mM with apparent Vmax values of 6.3 and 90 nmol/mg protein/min, respectively. The high affinity, low Km component resembles system ASC activity, with respect to substrate selectivity. The Na(+)-independent route also exhibits biphasic kinetics. A high affinity component (apparent Km of 1.0 mM, and apparent Vmax of 7.2 nmol/mg protein/min) is sensitive to inhibition by leucine and the aminoendolevo-rotatory isomer of 2 aminobicyclo[2,2,1]heptane-2-carboxylic acid, suggesting participation by system L. The low affinity component (apparent Km of 10.2 mM, and apparent Vmax of 71 nmol/mg protein/min) was specifically inhibited by threonine, serine, and alanine and could be assigned to system asc. The discrimination between system L and asc is based upon differences in pH sensitivity, trans stimulation, and Ki values. In addition, the effects of harmaline, a suspected sodium transport site inhibitor, have been studied. Harmaline noncompetitively inhibited Na(+)-dependent threonine uptake but had no effect on Na(+)-independent transport of threonine. This report is the first to present evidence for the presence of system asc in renal epithelial cells. The physiological and biochemical significance of our findings are discussed. PMID- 1907972 TI - Expression and characterization of human factor IX. Factor IXthr-397 and factor IXval-397. AB - Factor IXLong Beach has a single amino acid substitution at 397 (Ile to Thr) in the catalytic domain which results in severe hemophilia B. Recent investigations have shown that the substitution of threonine for isoleucine at 397 may affect a part of the macromolecular substrate binding site. Because threonine has a hydroxyl group in its side chain, it is possible that this hydroxyl group makes new hydrogen bonds and disturbs the substrate binding site. We used three techniques: molecular biology, which includes site-directed mutagenesis and recombinant protein expression in tissue culture; computer-aided kinetic data analysis; and molecular modeling to study this mutation site. We have produced two mutant factor IX molecules that have isoleucine 397 replaced by valine or threonine. Factor IXwild type and the two mutants (factor IXVal and factor IXThr) were expressed in human kidney cells and purified using a conformation-specific monoclonal antibody column. After the activation by factor XIa, these three molecules were able to bind p-aminobenzamidine and increase its fluorescence intensity in a similar manner. Factor IXVal and factor IXwild type had indistinguishable activities in an activated partial thromboplastin time (aPTT) assay and similar kinetic parameters with factor X as a substrate. Factor IXThr had only 5% clotting activity compared with normal factor IX, a slightly lower Km and significantly reduced kcat, using factor X as a substrate. We developed energy-refined (AMBER v.3.1) computer models of the three factor IX molecules based on previous work. Three factor IXa models (Ile, Val, or Thr at 397) with a fragment of the factor X activation site were used to predict the effect of the mutation at 397 and evaluate the significance of the new hydrogen bond thought to form between the side chain hydroxyl group of threonine 397 and the carbonyl oxygen of tryptophan 385. This new hydrogen bond would affect the position of an amide proton of adjacent glycine 386 which has been proposed to make a hydrogen bond with a backbone carbonyl oxygen of the P3 residue of factor X. In addition to the new hydrogen bond, there is significant movement in the side chain of tryptophan 385 between the factor IXawild type-factor X model and the factor IXaThr-factor X model that could interfere with substrate binding. This movement could be caused by the change in the molecular volume, the orientation of the side chain at 397, and the new hydrogen bond. PMID- 1907973 TI - Sec12p-dependent membrane binding of the small GTP-binding protein Sar1p promotes formation of transport vesicles from the ER. AB - Sec12p is an integral membrane protein required in vivo and in vitro for the formation of transport vesicles generated from the ER. Vesicle budding and protein transport from ER membranes containing normal levels of Sec12p is inhibited in vitro by addition of microsomes isolated from a Sec12p-overproducing strain. Inhibition is attributable to titration of a limiting cytosolic protein. This limitation is overcome by addition of a highly enriched fraction of soluble Sar1p, a small GTP-binding protein, shown previously to be essential for protein transport from the ER and whose gene has been shown to interact genetically with sec12. Furthermore, Sar1p binding to isolated membranes is enhanced at elevated levels of Sec12p. Sar1p-Sec12p interaction may regulate the initiation of vesicle budding from the ER. PMID- 1907974 TI - Reconstitution of GTP-binding Sar1 protein function in ER to Golgi transport. AB - In the yeast secretory pathway, two genes SEC12 and SAR1, which encode a 70-kD integral membrane protein and a 21-kD GTP-binding protein, respectively, cooperate in protein transport from the ER to the Golgi apparatus. In vivo, the elevation of the SAR1 dosage suppresses temperature sensitivity of the sec12 mutant. In this paper, we show cell-free reconstitution of the ER-to-Golgi transport that depends on both of these gene products. First, the membranes from the sec12 mutant cells reproduce temperature sensitivity in the in vitro ER-to Golgi transport reaction. Furthermore, the addition of the Sar1 protein completely suppresses this temperature-sensitive defect of the sec12 membranes. The analysis of Sar1p partially purified by E. coli expression suggests that GTP hydrolysis is essential for Sar1p to execute its function. PMID- 1907975 TI - Vinculin is essential for muscle function in the nematode. AB - Actin filaments in the body wall muscle of the nematode Caenorhabditis elegans are attached to the sarcolemma through vinculin-containing structures called dense bodies, Z-line analogues. To investigate the in vivo function of vinculin, we executed a genetic screen designed to recover mutations in the region of the nematode vinculin gene, deb-1. According to four independent criteria, two of the isolated mutants were shown to be due to alterations in the deb-1 gene. First, antibody staining showed that the mutants had reduced levels of vinculin. Second, the sequence of each mutant gene was altered from that of wild type, with one mutation altering a conserved splice sequence and the other generating a premature amber stop codon. Third, the amber mutant was suppressed by the sup-7 amber suppressor tRNA gene. Finally, injection of a cloned wild type copy of the gene rescued the mutant. Mutant animals lacking vinculin arrested development as L1 larvae. In such animals, embryonic elongation was interrupted at the twofold length, so that the mutants were shorter than wild type animals at the same stage. The mutants were paralyzed and had disorganized muscle, a phenotype consistent with the idea that vinculin is essential for muscle function in the nematode. PMID- 1907976 TI - Phosphorylation determines the binding of microtubule-associated protein 2 (MAP2) to microtubules in living cells. AB - The influence of phosphorylation on the binding of microtubule-associated protein 2 (MAP2) to cellular microtubules was studied by microinjecting MAP2 in various phosphorylation states into rat-1 fibroblasts, which lack endogenous MAP2. Conventionally prepared brain MAP2, containing 10 mol of endogenous phosphate per mol (MAP2-P10), was completely bound to cellular microtubules within 2-3 min after injection. MAP2 prepared in the presence of phosphatase inhibitors, containing 25 mol/mol of phosphate (MAP2-P25), also bound completely. However, MAP2 whose phosphate content had been reduced to 2 mol phosphate per mol by treatment with alkaline phosphatase in vitro (MAP2-P2) did not initially bind to microtubules, suggesting that phosphorylation of certain sites in MAP2 is essential for binding to microtubules. MAP2-P10 was further phosphorylated in vitro via an endogenously bound protein kinase activity, adding 12 more phosphates, giving a total of 22 mol/mol. This preparation (MAP2-P10+12) also did not bind to microtubules. Assay of the binding of these preparations to taxol stabilized tubulin polymers in vitro confirmed that their binding to tubulin depended on the state of phosphorylation, but the results obtained in microinjection experiments differed in some cases from in vitro binding. The results suggest that the site of phosphate incorporation rather than the amount is the critical factor in determining microtubule binding activity of MAP2. Furthermore, the interaction of MAP2 with cellular microtubules may be influenced by additional factors that are not evident in vitro. PMID- 1907977 TI - Stabilities of dobutamine, dopamine, nitroglycerin and sodium nitroprusside in disposable plastic syringes. AB - The solutions of dobutamine hydrochloride (5 mg/ml), dopamine hydrochloride (4 mg/ml), nitroglycerin (1 mg/ml) and sodium nitroprusside (1 mg/ml) in dextrose 5% injection were stable for 24 h when stored at 25 degrees C in 60-ml plastic syringes. For sodium nitroprusside, the syringes must be wrapped with aluminium foil (provided by the manufacturer), otherwise the loss in potency is very high (22%). There was no change in the pH values of dobutamine and dopamine solutions as well as sodium nitroprusside solutions in the prewrapped syringes. However, the pH value of nitroglycerin solutions decreased to 4.3 from 4.6 and that of sodium nitroprusside solutions in unwrapped syringes from 4.2 to 3.5; these solutions had discoloured. The chromatogram also showed new peaks from the products of decomposition. The physical appearances of the other solutions did not change. PMID- 1907978 TI - The actions of NSAIDs. AB - The ability of aspirin and related drugs to inhibit prostaglandin biosynthesis accounts for many effects of NSAIDs but does not completely explain their efficacy against inflammation. An additional mechanism may be disruption of the intracellular signal pathways responsible for activation of inflammatory cells- notably, neutrophils. PMID- 1907980 TI - Topical 2% mupirocin versus 2% sodium fusidate ointment in the treatment of primary and secondary skin infections. PMID- 1907979 TI - Hypophysiotrophic TRH-producing neurons identified by combining immunohistochemistry for pro-TRH and retrograde tracing. AB - To determine hypophysiotrophic thyrotropin-releasing hormone (TRH)-producing neurons in the rat hypothalamus, we employed a combination of the immunohistochemistry for TRH prohormone (pro-TRH) and the retrograde tracing of neurons that project to the median eminence (ME) by injecting biotinylated wheat germ agglutinin (WGA) into the ME. In intact rats, immunoreactive pro-TRH positive neurons occurred in the parvicellular paraventricular nucleus (parvi PVN), basal part of the anterior and lateral hypothalamus, perifornical area and dorsomedial nucleus, especially accumulating in the parvi-PVN. Twenty-four hours after injection of the WGA into the middle portion of the ME, we found neurons that incorporated the lectin in the anterior periventricular area, the PVN, and the arcuate nucleus. When we examined serial sections consecutively stained with anti-WGA, anti-pro-TRH, and anti-WGA, most of the pro-TRH-labeled neurons in the medial parvi-PVN and a part of the neurons in the anterior periventricular area and in the anterior, lateral, and dorsal parvi-PVN appeared to incorporate WGA. These neurons may correspond with the hypophysiotrophic TRH-synthesizing neurons in the rat hypothalamus. PMID- 1907981 TI - Juvenile xanthogranulomas with inconspicuous or absent foam cells and giant cells. PMID- 1907982 TI - Symphalangism and multiple neurofibromas. PMID- 1907983 TI - Preventive home visits to elderly people by community nurses in The Netherlands. AB - This study aims at a description of the current position of preventive home visits to the elderly by community nurses in The Netherlands. Over a period of 8 weeks, a representative sample of 108 community nurses and 49 community nursing auxiliaries at 47 different locations paid a total number of 215 preventive home visits to elderly people. Clients' characteristics, the nature of care delivered by the nurse, and the length of the home visit were recorded for each home visit. The results suggested that community nurses and nursing auxiliaries spent very little time on preventive home visits. During the home visits, both types of nurses tried to increase the self-care agency of the elderly by giving education or advice. Furthermore, community nurses often paid more attention to the assessment and examination of existing or emerging self-care deficits of the elderly people visited than nursing auxiliaries. In spite of the fact that the importance of preventive care for the elderly is recognized, resources are scarce. It is therefore recommended that more research be carried out on the cost effectiveness of preventive home visits. PMID- 1907984 TI - Routine programmed electrical stimulation in survivors of acute myocardial infarction for prediction of spontaneous ventricular tachyarrhythmias during follow-up: results, optimal stimulation protocol and cost-effective screening. AB - Of 3,286 consecutive patients treated for acute myocardial infarction, electrophysiologic testing was performed in 1,209 survivors (37%) free of significant complications at the time of hospital discharge to determine their risk of spontaneous ventricular tachyarrhythmias during follow-up. Sustained monomorphic ventricular tachycardia was inducible by programmed electrical stimulation in 75 (6.2%). Antiarrhythmic therapy was not routinely prescribed regardless of the test results. During the 1st year of follow-up, 14 infarct survivors (19%) with inducible ventricular tachycardia experienced spontaneous ventricular tachycardia or fibrillation in the absence of new ischemia compared with 34 (2.9%) of those without inducible ventricular tachycardia (p less than 0.0005). During the extended follow-up period (median 28 months) of those with inducible ventricular tachycardia, 19 (25%) had a spontaneous electrical event; 37% of these first events were fatal. These results suggest that the most cost effective strategy for predicting arrhythmia will be obtained by restricting electrophysiologic testing to infarct survivors whose left ventricular ejection fraction is less than 40% and using a stimulation protocol containing four extrastimuli. Electrophysiologic testing is the single best predictor of spontaneous ventricular tachyarrhythmias during follow-up in infarct survivors. The majority (94%) with a negative test benefit from the more reliable reassurance that all is well, whereas the 25% risk of electrical events in those with inducible ventricular tachycardia justifies a prospective trial of effective prophylactic antiarrhythmic interventions. PMID- 1907985 TI - Alternative lipid sources for enteral and parenteral nutrition: long- and medium chain triglycerides, structured triglycerides, and fish oils. AB - This article reviews current investigations of the use of alternative lipid sources to enhance the metabolic and immune functions of hospitalized patients. Conventional lipids have been implicated as the cause of a variety of iatrogenic side effects in critically ill hospitalized patients, and long-chain triglycerides of the omega-6 family have been shown to be potentially detrimental to immune function. Alternative lipids (fish oils, medium-chain triglycerides, and structured triglycerides) have been proposed as substitutes for conventional long-chain, polyunsaturated omega-6 fatty acids. Unlike long-chain triglycerides, medium-chain triglycerides are more rapidly cleared from the blood and are completely oxidized for energy. However, medium-chain triglycerides contain no essential fatty acids. On the other hand, structured triglycerides offer the advantages of long-chain triglycerides (essential fatty acids) and of medium chain triglycerides (rapid clearance and oxidation). Fish oils, which contain long-chain polyunsaturated omega-3 fatty acids, appear to be anti-inflammatory and to affect immune function differently from the omega-6 long-chain triglycerides. PMID- 1907986 TI - Carotid chemosensory timing effects on cervical sympathetic discharges in the cat. AB - The hypothesis that respiratory phase-related sympathetic nerve activity would manifest timing effect of carotid chemosensory input with respect to the central respiratory drive was tested in the anesthetized, paralyzed and artificially ventilated cats which were also vagotomized and tracheostomized. Preganglionic cervical sympathetic nerve fibers (PSNF) which were clearly responsive to carotid chemosensory stimulation were selected for the test. Simultaneously with the PSNF, phrenic nerve (PN) and internal intercostal expiratory nerve (IICEN) activities were also recorded. In most instances, carotid chemosensory discharges were monitored in order to register the precise timing of its input to the brain stem. Timed stimulation of carotid chemoreceptors was elicited by bolus injections of cyanide (10-20 micrograms), nicotine (10-20 micrograms) and CO2 saturated saline (0.2-0.5 ml) into the base of the common carotid artery. Two types of PSNFs were identified: type I discharged only in synchrony with the PN activity (13/47) and type II fired independently of, but entrained to, PN activity (34/47). Type I displayed characteristic timing effects of carotid chemoreflex on PN discharges. However, the sympathetic activity did not share the after-discharge of PN which persisted beyond the carotid chemoreceptor stimulation. Type II did not manifest any timing effect of carotid chemoreflex with respect to PN and IICEN activities. These results suggest the following model of carotid chemoreflex effects on sympathetic neuron activities: a group is exclusively gated by the properties of central respiratory drive whereas the other is not gated but entrained by it in the spontaneously breathing anesthetized cat. PMID- 1907987 TI - Microcomputer applications for primary health care in developing countries. AB - This article explores some ways in which computer technology can be harnessed to strengthen primary health care planning and management, make more efficient use of scare health resources, and maximize the beneficial impact on health of local, district, and national health systems in both developing and developed countries. PMID- 1907988 TI - Aging. AB - Many issues are emerging as a consequence of the aging of modern populations. Developed as well as developing countries need to define the policies and programs that will reduce the burden of aging populations on societies and their economies, ensure the availability of health and social services for older persons, and promote their continuing participation in a socially and economically productive life. The situation is more challenging for developing countries, which must add new priorities to the scarce resources of their health and social programs when they still have to deal with the problems of their younger population. The World Health Organization is collaborating with the member states to find solutions that are adequate to their own situation. Promotion of research that will provide policymakers with data on the actual needs of their aging population is the main objective of the WHO international research program on aging. PMID- 1907989 TI - Microfilament assembly is required for antigen-receptor-mediated activation of human B lymphocytes. AB - The mechanisms responsible for initiating the conversion of globular to filamentous actin (assembly) after stimulation of B lymphocytes and the role of these cytoskeletal changes in cell activation are incompletely understood. We investigated the molecular basis of the signals leading to actin polymerization and concentrated on the involvement of guanosine triphosphate (GTP)-binding regulatory proteins, and protein kinase C (PKC). In addition, we related these early events to later events in B-cell activation, including cell proliferation. Cross-linking the Ag receptor with Staphylococcus aureus Cowan I (SAC) or anti IgM antibodies, or stimulation of PKC with phorbol ester induced a time- and concentration-dependent increase in the filamentous actin content of B cells. Inhibition or depletion of PKC resulted in decreased actin assembly induced by anti-IgM, SAC, and PMA, suggesting that the signal for polymerization is generated distally to PKC activation. Pertussis toxin pretreatment inhibited the responses to anti-IgM and SAC but not PMA, and direct stimulation of permeabilized cells with GTP gamma S induced microfilament assembly, indicating the involvement of a GTP-binding protein for receptor-mediated events. Disruption of actin polymerization with botulinum C2 toxin or cytochalasin D inhibited the assembly of actin and [3H]TdR incorporation induced by all stimuli. We conclude that human B cell activation by receptor-mediated stimuli results in actin polymerization by signaling pathways coupled to GTP-binding proteins. These changes in the cytoskeleton may be involved in the transduction of messages leading to responses such as proliferation in B lymphocytes. PMID- 1907990 TI - Role of a thymic stromal cell clone in inducing the stage-specific differentiation of various subpopulations of double negative thymocytes. AB - The monolayer of a thymic stromal cell clone termed MRL104.8a induced the differentiation of adult double negative (DN) thymocytes (CD3-4-8-) through a CD3 4-8+ intermediate into CD3- (or dull) 4+8+ stages. DN thymocytes were separated into three subpopulations depending on their cell-surface expression of Pgp-1 and IL-2R, namely, Pgp-1+IL-2R-, Pgp-1-IL-2R+, and Pgp-1-IL-2R-. The present study investigated the requirements of the MRL104.8a monolayer for inducing the differentiation of these DN thymocyte subpopulations. The following were revealed: i) the MRL104.8a monolayer failed to induce the differentiation of a Pgp-1+IL-2R- subpopulation; ii) whereas a Pgp-1-IL-2R+ subpopulation did not express either CD4 or CD8 Ag when cultured in medium, culturing this subpopulation on the thymic stromal cell monolayers resulted in the expression of CD8 but not CD4 Ag; and iii) a Pgp-1-IL-2R- DN subpopulation obtained through less extensive treatments with anti-CD4 and anti-CD8 antibodies in the presence of C before sorting procedures spontaneously differentiated into double positive cells in medium. In contrast, most of DN cells with the same phenotype obtained through extensive anti-CD4 and -CD8 treatments before sorting failed to express CD4 and/or CD8 Ag in medium but could differentiate through a CD3-4-8+ into more mature stages only when they were cultured on the thymic stromal monolayer. These results indicate differential requirements of thymic stromal cells for the differentiation of various DN subpopulations with qualitatively distinct phenotypes and different magnitudes (very low vs almost zero levels) of CD4/CD8 expression. PMID- 1907991 TI - Cross-linkage of Ly-6A/E induces Ca2+ translocation in the absence of phosphatidylinositol turnover and mediates proliferation of normal murine B lymphocytes. AB - Ly-6A/E is a phosphatidylinositol (PI)-linked membrane protein whose expression is induced or upregulated on normal murine T and B cells by IFN-gamma. Cross linkage of Ly-6A/E expressed on normal murine T cells stimulates Ca2+ translocation, and in the presence of a protein kinase C (PKC) activator, lymphokine secretion, and cellular proliferation. Utilizing an anti-Ly-6A/E mAb, we studied the effect of cross-linking Ly-6A/E on IFN-gamma-treated resting B cells, for Ca2+ translocation, PI turnover, and cellular proliferation. Since these events are known to be stimulated by cross-linkage of B cell membrane (m)Ig, we compared the changes mediated through these respective membrane proteins. We show that cross-linkage of B cell Ly-6A/E stimulates a large, rapid, and sustained increase in the concentration of intracellular free calcium ([Ca2+]i) comparable in magnitude, though somewhat delayed, relative to that observed after cross-linking of mIg. Cross-linkage of B cell Ly-6A/E does not, however, stimulate detectable PI turnover, in contrast to PI turnover induced by ligation of mIg. Both the Ly-6A/E- and mIg-mediated increase in [Ca2+]i occur through mobilization of internal Ca2+ stores as well as entry of Ca2+ into the cell from the extracellular compartment. Ly-6A/E-mediated Ca2+ translocation appears to be under the regulation of PKC in that short term pretreatment of B cells with the PKC activator, PMA, inhibits the Ly-6A/E- as well as the mIg mediated increase in [Ca2+]i, whereas prolonged exposure to PMA, under conditions that lead to depletion of PKC, results in an augmentation in Ca2+ translocation after ligation of either Ly-6A/E or mIg. Co-capping studies indicate that Ly-6A/E and mIg cap independently in the B cell membrane, thus suggesting that the Ly 6A/E-induced effects on Ca2+ translocation are not mediated through simultaneous modulation of mIg. Anti-Ly6A/E, by itself, does not stimulate an increase in [3H]thymidine incorporation by IFN-gamma-treated resting B cells, but induces a striking increase in the presence of PMA. By contrast, anti-Ig by itself stimulates significant increases in [3H]thymidine incorporation that is inhibited by PMA. Thus, Ly-6A/E is a potent mediator of B cell activation that may use a signal transduction system in quiescent B cells that is distinct from that of the Ag receptor. PMID- 1907992 TI - Role of Mls-1 locus and clonal deletion of T cells in susceptibility to collagen induced arthritis in mice. AB - The role of T cell-mediated and humoral immunity to type II collagen has been well documented in collagen-induced arthritis (CIA). Previous work from our laboratory has indicated that genomic deletions of TCR V beta genes may play a role in CIA resistance in mice. This indicated a selectivity of TCR usage by autoreactive T cells in CIA in mice. Certain strains of mice, although having a normal genomic V beta TCR repertoire, can show clonal deletion of peripheral T cells that bear specific V beta gene products in their TCR. These clonally deleted T cells are reactive with self-Ag such as minor lymphocyte stimulation (Mls) Ag. An Mls-congenic strain, BALB.D2.Mlsa, which differs only at the Mls-1 a locus from BALB/c (Mls-1b), was used to examine the effect of clonal deletion of Mls-1a-reactive T cells in CIA. These two strains were crossed to three CIA susceptible strains, B10.RIII (H-2r, Mls-1b), DBA/1 (H-2q, Mls-1a), and B10.Q (H 2q, Mls-1b), and the crosses were injected with type II collagen. A significantly decreased incidence of arthritis was observed in the (BALB.D2.Mlsa x B10.Q)F1 hybrids, compared with (BALB/c x B10.Q)F1 hybrids, upon immunization with chick type II collagen. The BALB.D2.Mlsa cross mice also had significantly lower levels of antimouse collagen antibodies. Flow cytometric analysis confirmed the clonal deletion of Mls-1a-reactive V beta 8.1, V beta 6, V beta 7, and V beta 9 subsets in the (BALB.D2.Mlsa x B10.Q)F1 hybrids. The study of H-2q/d mice in (BALB.D2.Mlsa x B10.Q) x B10.Q back-crosses demonstrated a significant correlation between CIA resistance and Mls-1a locus. On the other hand, B10.RIII crosses showed only a modest decrease in CIA incidence in the presence of Mls-1a. As expected, all the DBA/1 crosses had an equal incidence of CIA, which was somewhat less than that seen in DBA/1 mice themselves. These studies point out that the Mls-1a locus could play a role in decreasing CIA incidence by clonal deletion of T cells bearing specific V beta TCR, which may be involved in the pathogenesis of CIA. The influence of the clonal deletion of T cells on CIA, and hence the usage of specific V beta TCR by autoreactive anti-type II collagen T cells, however, depends not only on the source of the type II collagen and the MHC class II molecules involved but also on other background genes in mice. PMID- 1907993 TI - Abnormal regulation of IFN-gamma secretion in vitamin A deficiency. AB - T lymphocytes from vitamin A-deficient (A-) mice show a decreased ability to stimulate B lymphocytes for Ag-specific secondary IgG1 responses in vivo and in vitro. Experiments reported here traced the molecular basis for this functional defect to an overproduction of IFN-gamma by A- CD4+ T cells compared with cells from A-sufficient (A+) mice. Secretion of IL-2 and IL-4 by cells from A- and A+ mice was equivalent. Retinoic acid supplementation in vitro decreased IFN-gamma secretion from A- T cells, indicating that IFN-gamma production is retinoid responsive. Adding IFN-gamma neutralizing antibodies to cultures established with cells from immune A- mice substantially increased IgG1 production, whereas IL-4 addition moderately increased IgG1 production. Adding retinoic acid to the cultures either at initiation, or 48 h later, fully restored IgG1 production by A cultures to the level of A+ control cultures. These results are consistent with a role for vitamin A in negatively regulating IFN-gamma secretion. PMID- 1907994 TI - Reconstitution of a deficiency of AKR mouse macrophages for their response to lipid A activation for tumor cytotoxicity by complement subcomponent C1q: role of IFN-gamma. AB - C5-deficient AKR mouse macrophages were initially found to be refractory to activation by lipid A to mediate tumor cytotoxicity for P815 mastocytoma or L1210 mouse leukemia targets as compared with responsive C3H mouse macrophages. The lower level of tumor cytotoxicity by lipid A-activated AKR macrophages correlated with lower levels of cytotoxic nitric oxide generation as measured by nitrite end product accumulation. The refractory state of AKR macrophages was unexpectedly found to be independent of their C5 deficiency in that IFN-gamma reconstituted their response to activation by lipid A coincident with an increase in C1q mRNA synthesis. AKR macrophages were augmented in their lipid A activation by exogenous soluble C1q in the absence of IFN-gamma, which corresponded with an increased production of nitric oxide by C1q-reconstituted macrophages. In contrast, responsive C3H mouse macrophages with sufficient levels of C1q synthesis were inhibited by exogenous soluble monomeric C1q in their lipid A activation. Both AKR and C3H macrophages plated over immobilized C1q were inhibited in their lipid A activation for tumor cytotoxicity and nitric oxide generation. Our results provide evidence that C1q modulates macrophage activation by lipid A for nitric oxide-mediated tumor cytotoxicity under the influence of IFN-gamma, which stimulates C1q synthesis and secretion. These findings strongly suggest that macrophage synthesis of C1q, but not C5, is a prerequisite for their activation by lipid A. PMID- 1907995 TI - A single amino acid substitution in an MHC class I molecule allows heteroclitic recognition by lymphocytic choriomeningitis virus-specific cytotoxic T lymphocytes. AB - Class I molecules of the MHC bind foreign and endogenous peptides allowing recognition by the TCR on CTL. The recognition and killing of cells infected with lymphocytic choriomeningitis virus (LCMV) depends on the recognition of LCMV peptides bound to class I MHC. Mutations in class I MHC molecules have enabled the delineation of regions in the class I molecule important for binding peptides and for interaction with the TCR. We have constructed a library of class I mutants using saturation mutagenesis and report a phenotypic change resulting from a single amino acid substitution that results in the heteroclitic (increased) killing of LCMV-infected cells. This amino acid change, asparagine to serine at position 30, is in a conserved region of the class I molecule contacting the alpha 3 domain. This mutation does not result in increased expression of the class I molecule on the cell surface, does not affect the binding of CD8, and does not affect allogeneic recognition. Cold target experiments show that this heteroclitic killing is due to increased recognition by CTL. These data point toward a critical function for this region of the class I molecule in the binding of peptides or their presentation to CTL. PMID- 1907996 TI - Control of T cell responses to staphylococcal enterotoxins by stimulator cell MHC class II polymorphism. AB - The bacterial toxic mitogens or superantigens are a family of related proteins that elicit potent T cell proliferative responses. These responses require APC that express MHC class II proteins, but they are not MHC restricted and they do not depend on a processing step, presumably because these mitogens bind directly to MHC class II molecules. These mitogens stimulate T cells by interacting in an unknown way with the portion of the TCR encoded by certain V beta gene segments. In this paper, we explore the importance of MHC class II polymorphism in T cell responses to staphylococcal enterotoxins. We find that certain MHC molecules present SEB to V beta 8-bearing T cells far better than others. These data suggest that one route of host defence against bacterial toxic mitogens may be to alter MHC class II molecules so that stimulation is inhibited. PMID- 1907997 TI - Predominance of nonproductive rearrangements of VH81X gene segments evidences a dependence of B cell clonal maturation on the structure of nascent H chains. AB - Ig H chain V regions using the VH81X gene segment were PCR amplified from genomic DNA obtained from either splenic B cells or surface (s)Ig- bone marrow cells of BALB/c mice. Sequence analysis demonstrated that 93% of VH81X containing H chain V region genes in splenic B cells were rearranged nonproductively. Furthermore, 74% of rearrangements of VH81X among sIg- bone marrow cells were nonproductive. This contrasts with previous results obtained for rearrangements of members of the VH36-60 gene segment family among sIg- cells wherein, as a consequence of extensive clonal expansion after productive H chain V gene rearrangement, 80% of rearrangements were productive. The low proportion of productive rearrangements of VH81X is interpreted as indicating that most productive rearrangements of VH81X cannot facilitate clonal expansion, which would support the hypothesis that selection for clonal expansion and maturation is dependent on the amino acid sequence of nascent H chains. Additionally, because most productive rearrangements of VH81X cannot facilitate clonal maturation but do appear to mediate allelic exclusion, these processes are likely to be regulated independently. PMID- 1907998 TI - Mechanism of cytolytic T lymphocyte killing of a low class I-expressing tumor. AB - Many tumors have been shown to express minimal levels of class I MHC Ag, which makes them more resistant to recognition and lysis by cytolytic T lymphocytes. Line 1, a BALB/c spontaneous lung carcinoma, normally expresses very low levels of class I Ag, but expression can be increased 50-fold by treatment with agents such as DMSO or IFN-gamma. Because class I Ag serve as restricting elements for cytolytic T cell recognition of tumor Ag, we wished to determine if cytotoxic T lymphocytes could play a role in the immune response to this type of class I low, but inducible, tumor. After immunization in vivo and restimulation of splenic cells in vitro we were able to generate T cell clones that lysed line 1 cells induced to express high levels of class I, but did not lyse uninduced, low class I expressing line 1 cells in short term (6-h) 51Cr release assays. Paradoxically, incubation of the T cells with uninduced class I low line 1 cells for a few days resulted in complete destruction of the tumor cells. We demonstrate that the T cells, stimulated by the tumor cells, produce IFN-gamma, which in turn induces class I expression on the line 1 cells making them susceptible to lysis by the T cell clone. This suggests that a positive feedback reaction can occur in generating a response to this and perhaps other inducible tumor cell lines. PMID- 1908000 TI - Combination therapy with ciprofloxacin plus azlocillin against Pseudomonas aeruginosa: effect of simultaneous versus staggered administration in an in vitro model of infection. AB - The effect of dose scheduling on the pharmacodynamics of simulated human doses of ciprofloxacin (200 mg intravenously [iv] every 12 h) and azlocillin (4 g iv every 12 h) alone or in combination against Pseudomonas aeruginosa was studied in a two compartment in vitro kinetic model of infection. Studies with the two drugs in combination were compared using simultaneous or staggered (first doses of each drug were administered 6 h apart) dosing schedules. Bacterial regrowth and resistance were prevented by all combination dosing schedules; however, the simultaneous regimen consistently provided the greatest extent of killing for all strains, particularly in those initially resistant to ciprofloxacin. These enhanced effects of the combination were corroborated by an increase in the peak and duration of bactericidal activity in the analogous "serum" compartment of the model. These data show the potential usefulness of simultaneous dosing of an antipseudomonal beta-lactam with ciprofloxacin against P. aeruginosa. PMID- 1907999 TI - Defective presentation of endogenous antigens by a murine sarcoma. Implications for the failure of an anti-tumor immune response. AB - MHC class I-restricted CTL play a central role in the immune response against methylcholanthrene (MCA)-induced sarcomas in mice. We, therefore, hypothesized that MCA-induced tumors may evade immune recognition by failing to present Ag to CD8+ CTL. Of a number of previously described MCA-induced sarcomas, one, MCA 101, fails to induce CTL, is nonimmunogenic, and grows rapidly and lethally in nonimmunosuppressed recipients. To better understand the nonimmunogenicity of MCA 101 we examined its ability to present foreign Ag to CTL. Unlike immunogenic sarcomas, MCA 101 failed to present endogenously synthesized influenza virus Ag to influenza virus-specific CTL. The deficiency in presentation of endogenous Ag by MCA 101 was attributed to a markedly reduced rate of synthesis of class I molecules because up-regulation of class I synthesis by IFN-gamma greatly increased the presentation of influenza A virus Ag. Despite low levels of cell surface class I expression, MCA 101 presented exogenous peptide Ag to anti influenza CTL with efficiency similar to immunogenic MCA sarcoma cell lines. These findings could not be attributed to deficiencies in class I assembly or transport, as has been suggested by others who have studied mutant cells with defective Ag presentation. Furthermore, our studies suggest that some tumor cells can escape recognition by CTL and subsequent immune eradication by suppressing presentation of endogenous Ag. PMID- 1908001 TI - Effect of polymyxin B on experimental shock from meningococcal and Escherichia coli endotoxins. AB - Meningococcemia is the most frequent cause of septic shock in healthy children. To determine whether polymyxin B (PMB) might improve mortality from meningococcal shock, its protective activity was evaluated in rabbits challenged with an LD90 of meningococcal lipooligosaccharide (LOS) and compared with an LD80 of Escherichia coli O111:B4 lipopolysaccharide (LPS). PMB (5 mg/kg) administered intravenously 30 min before meningococcal LOS challenge had no significant effect on heart rate, mean arterial pressure, serum bicarbonate, serum tumor necrosis factor (TNF) levels, or survival relative to controls. However, PMB premixed with LOS in vitro increased serum bicarbonate levels (P less than .05) and improved 24 h survival (P less than .05). In contrast, PMB given before E. coli LPS challenge increased serum bicarbonate levels, decreased TNF levels, and improved 24-h survival (all, P less than .05). In vitro studies confirmed that PMB at 10 micrograms/ml neutralized E. coli LPS but not meningococcal LOS activity. Thus, pretreatment with PMB apparently protects rabbits against shock induced by E. coli LPS but not by meningococcal LOS. PMID- 1908002 TI - Cytokines and the pathogenesis of neuroborreliosis: Borrelia burgdorferi induces glioma cells to secrete interleukin-6. AB - Lyme disease is a multisystemic disease caused by a tickborne spirochete, Borrelia burgdorferi. Neuroborreliosis is characterized by intrathecal production of antibodies specific for the spirochete. This suggests that spirochetal infection of the central nervous system produces conditions that support the maturation of B lymphocytes to immunoglobulin-secreting cells. Interleukin 6 (IL 6) stimulates B cell differentiation into antibody-secreting cells. The present study was undertaken to determine whether B. burgdorferi can stimulate cells of central nervous system origin to secrete IL-6. C6 rat glioma cells cultured with spirochetes induced secretion of IL-6 activity. Peak stimulation was achieved at 24 h with 25 spirochetes per glioma cell. Glioma cells were also stimulated to produce IL-6 by interleukin 1 and tumor necrosis factor. That very few spirochetes are found in Lyme disease patients suggests that biologic amplification factors derived from the organism or the host, or both, are responsible for the pathogenesis of this disease. IL-6 can now be added to the growing list of such factors. PMID- 1908003 TI - Kinetics of the biosynthesis of complement subcomponent C1q by murine macrophages: effects of stimulation by interferon-gamma. AB - The effects of interferon-gamma (IFN-gamma) on the kinetics of biosynthesis of complement subcomponent C1q by mouse inflammatory peritoneal macrophages were determined. Stimulation of macrophages with various concentrations of IFN-gamma produced a dose-dependent increase in C1q mRNA accumulation which was detected as early as 3 h and sustained through 24 h, as determined by Northern blot analysis. A corresponding early increase in the extracellular accumulation of functional C1q was detected in culture supernatants after 3-9 h stimulation of macrophages with IFN-gamma that was sustained for 24-48 h as determined by a complement hemolytic assay. Autoradiographic analysis of [35S]methionine-labeled secretory C1q confirmed the protracted dose-dependent secretion of C1q by IFN-gamma stimulated macrophages during 24-48 h of culture. Western blot analysis of macrophage lysates indicated no significant changes in endogenous C1q levels following stimulation with IFN-gamma either after 3-9 h or 24-48 h when both C1q mRNA and extracellular accumulation were at their peak. Our results indicate that IFN-gamma promotes early and protracted mRNA accumulation and secretion of C1q by macrophages without intracellular accumulation, presumably due to the rapid rate of secretion of newly synthesized C1q. It is apparent that priming of macrophages with IFN-gamma provides a rapid and abundant source of secretory C1q for potential interaction with various macrophage triggering agents which also bind C1q. PMID- 1908004 TI - Uptake of extracellular Ca2+ is a requirement for production of interferon-gamma by cord blood mononuclear cells. AB - We studied the response of adult peripheral and cord blood mononuclear cells (MNCs) to graded concentrations of phytohemagglutinin (PHA) to characterize the requirements for proliferation and interferon-gamma (IFN-gamma) production. As the concentration of PHA was decreased, the proliferative response of both adult and cord blood MNCs decreased in parallel. At high concentrations of PHA (a: 120) cord blood MNCs display normal high proliferation but IFN-gamma production was greatly diminished compared with adult MNCs. Addition of the calcium ionophore, A23187, to PHA-stimulated adult MNCs had no effect on proliferation or IFN-gamma production at any of the concentrations of PHA tested. Furthermore, A23187 alone had no effect on proliferation or IFN-gamma secretion. Similarly, the addition of A23187 to PHA-stimulated cord-blood MNCs had no effect on proliferation. However, when A23187 was added to high dose (1:120) PHA-stimulated cord blood MNCs IFN gamma production increased to levels comparable with adult PHA-stimulated MNCs. A similar pattern of response was seen when exogenous calcium chloride was added in place of A23187. PMID- 1908006 TI - c-fos mRNA, Fos, and Fos-related antigen induction by hypertonic saline and stress. AB - The induction of c-fos mRNA was assessed using Northern blots and in situ hybridization in adult rats administered hypertonic saline (HS) and isotonic saline (IS). HS induced c-fos mRNA in magnocellular paraventricular nucleus (PVNm), parvocellular paraventricular nucleus (PVNp), supraoptic nucleus (SON), and lamina terminalis (LMT). This occurred within 5 min, peaked at 30-60 min, and disappeared by 180 min. Fos protein, detected using a specific monoclonal antibody, was maximal at 1-2 hr and disappeared 4-8 hr after HS administration. This confirms observations showing that the c-fos gene response is transient even in the presence of a continuing stimulus. In contrast, Fos-like immunoreactivity (FLI), detected using two polyclonal antisera, was observed in PVNm, PVNp, SON, and LMT for 1-24 hr during continuous osmotic stimulation. Moreover, FLI was observable in these structures for 7 d in rats administered HS and allowed to drink water ad libitum beginning 24 hr later. At times greater than 8 hr, FLI presumably represents Fos-related antigens (FRA), proteins immunologically and functionally related to Fos, whose expression is much more prolonged than authentic Fos following the osmotic stimulus. In addition to induction of c-fos expression in regions specifically involved in osmotic regulation, HS injections also induced c-fos in many other forebrain regions. In order to assess the induction of c-fos mRNA due to the "stress" of the injections, rats injected with isotonic saline were compared to uninjected controls. Isotonic saline injections induced c-fos mRNA in the PVNp, anterior hypothalamus, suprachiasmatic nucleus, cingulate gyrus, neocortex, ventral lateral septal nucleus, piriform cortex, hippocampal pyramidal and dentate granule neurons, paraventricular and intralaminar thalamic nuclei, bed nuclei of stria terminalis, cortical and medial amygdaloid nuclei, and other structures. In accord with other work, we interpret this pattern of c-fos expression to result from the stress of handling and injections. Since Fos and FRA probably bind to the promoters of target genes and regulate their expression, they likely mediate biochemical changes in the cells activated by the osmotic and stressful stimuli. Whereas the Fos signal is transient, FRA may act on target genes for the duration of the stimulus or longer. PMID- 1908007 TI - Radiocesium levels in humans over a four-year period. AB - Following the Chernobyl accident, Austria was one of the most contaminated Western European countries. Predictions of internal dose in humans due to this contamination were based on the average activities in major dietary products and average consumption rates. We have measured the amount of radiocesium in human adult muscle samples obtained at forensic autopsies within a limited area in Southern Austria over a period of 4 yr. From the measurements, we have estimated a mean individual effective dose equivalent of 252.2 muSv (25.2 mrem) due to internal exposure to radiocesium during this 4-yr period. This estimate, based on actual measurements, is approximately 25% of the predicted dose and is less than 50% of the dose received in the body from naturally occurring potassium-40. Comparisons of radiocesium activities measured in muscle tissues with data obtained after nuclear weapons tests and whole-body countings are given. PMID- 1908005 TI - Muscle mitochondrial DNA in encephalomyopathy and ragged red fibres: a Southern blot analysis and literature review. AB - Various mitochondrial DNA abnormalities have been described in patients with encephalomyopathies. We performed Southern blot analysis of skeletal muscle mitochondrial DNA in nine adult patients with clinical features and ragged red fibres suggesting mitochondrial dysfunction. Two patients with encephalomyopathy and two with the MERRF syndrome (myoclonus epilepsy with ragged red fibres) had the normal PvuII restriction pattern of muscle mitochondrial DNA. In contrast, mitochondrial DNA deletion was observed in two of six patients with ophthalmoplegia. One suffered from typical Kearns-Sayre syndrome and the other from isolated external ophthalmoplegia. None of these patients had affected relatives. The detection of mitochondrial DNA deletion in external ophthalmoplegia and their site and size support previously reported data. PMID- 1908008 TI - Managing end-stage renal disease. PMID- 1908009 TI - Segregation and sporadic cases in families with Hunter's syndrome. AB - Segregation analysis on five samples of families with Hunter's syndrome (158 cases overall) shows that the mutant allele segregates in agreement with Mendelian expectations for an X linked recessive disease, but the proportion of sporadic cases is significantly lower than expected under mutation-selection equilibrium. Heterogeneity among the samples is apparent, but it is caused entirely by a sample of Ashkenazi families, whose segregation pattern has previously been interpreted as supporting the hypothesis of prenatal selection in favour of the pathological allele. Conversely, our joint analysis of the five samples by a maximum likelihood approach does not suggest segregation distortion. Possible reasons for the apparent lack of sporadic cases include the effect of ascertainment bias. PMID- 1908010 TI - Sanfilippo syndrome type D in two adolescent sisters. AB - We report on two adolescent sisters with Sanfilippo syndrome type D with some clinical features different from other cases previously described. They are the oldest cases reported to date and provide new clues about the course of the disease. Enzymatic and immunological characterisation of the patients' fibroblasts indicated deficiency of N-acetylglucosamine-6-sulphate sulphatase (GlcNAc-6S sulphatase). However, Northern blot analysis showed apparently normal mRNA encoding GlcNAc-6S sulphatase. These findings suggest that abnormal translation or premature degradation may be responsible for the enzyme defect in these cases of Sanfilippo syndrome type D. PMID- 1908011 TI - Elemental composition of pyroantimonate precipitates analysed by electron spectroscopic imaging (ESI) and electron energy-loss spectroscopy (EELS) in vitellogenic ovarian follicles of Drosophila. AB - Ca2+ was precipitated with potassium antimonate in vitellogenic follicles of the fruit fly Drosophila melanogaster and the distribution of the precipitates formed was studied by electron microscopy. The microvilli of the oolemma in mid- and late vitellogenic follicles were lined with precipitates. The chemical composition of the precipitates was analysed by electron spectroscopic imaging (ESI). The images produced by inelastically scattered electrons at specific ionization edges were compared, and the non-specific background signals were subtracted by an image processing system. The presence of Ca2+, antimony and oxygen in the precipitates formed could be demonstrated. The elemental composition of the precipitates and of yolk spheres was also analysed by electron energy-loss spectroscopy (EELS). With respect to the precipitates, signals at the calcium L2,3-edge, the oxygen K-edge and the antimony M4,5-edge were recorded without deconvolution and background subtraction. The yolk spheres, which were free of precipitates, gave the characteristic signal of the nitrogen K-edge. The applied techniques combine good ultrastructural resolution with the possibility of analysing the elemental composition of histochemical reaction products and cellular structures. PMID- 1908012 TI - Improved preservation of phospholipid-rich multilamellar bodies in conventionally embedded mammalian lung tissue--an electron spectroscopic study. AB - Different conventional methods of tissue processing were studied to determine the extent to which phospholipid-rich multilamellar bodies of pulmonary alveolar epithelial type II cells of the pig were preserved. Prolonged treatment with half saturated aqueous uranyl acetate yielded excellent results on the stabilization of the multilamellar substructure, irrespective of whether glutaraldehyde paraformaldehyde or glutaraldehyde-tannic acid was used as a primary fixative. The lamellar periodicities were observed to be 5.5-6.1 nm. Differences in the phosphorus distribution among several types of lipid bodies of alveolar epithelial type II cells were studied by means of electron spectroscopic imaging and electron energy-loss spectroscopy. Multilamellar bodies gave phosphorus signals which were significantly higher than those obtained from granular regions of composite bodies, whereas homogeneous bodies gave phosphorus signals which were even lower than those obtained from mitochondria, endoplasmic reticulum membranes or ribosomes. PMID- 1908013 TI - Complete physical map of the Bacillus subtilis 168 chromosome constructed by a gene-directed mutagenesis method. AB - All the SfiI sites and most of the NotI sites were located precisely on the chromosome of Bacillus subtilis 168 by a novel method, termed gene-directed mutagenesis. The stepwise elimination of these restriction sites by this method allowed not only the physical connection of the restriction fragments but also the accurate determination of the position of the restriction sites themselves. The resulting physical map of the 4165 x 10(3) base-pair B. subtilis chromosome has been correlated with the genetic map by determination of the exact location of known genes. The complete physical map provides a rapid and accurate way for mapping of new genes as well as analysis of large DNA rearrangements on the chromosome. The novel strategy is, in principle, applicable to the analysis of the genome of other organisms. PMID- 1908014 TI - Identification and characterization of Drosophila melanogaster paramyosin. AB - Paramyosin, a major structural component of thick filaments in invertebrates has been isolated, purified and characterized from whole adult Drosophila melanogaster extracts and a specific polyclonal antibody against it has been prepared. Paramyosin has been identified on the basis of several criteria, including molecular weight, alpha-helicity, species distribution, capability of fiber formation in vitro and sequence. We have used the immunopurified polyclonal antibody to isolate eight clones from a lambda gt11 expression library of Drosophila 1 to 22 h embryo cDNA. The largest clone (pJV9) has been sequenced and encodes the coiled-coil region of D. melanogaster paramyosin that is 47% identical to Caenorhabditis elegans paramyosin. Indirect immunofluorescence in semi-thin sections of adult flies show fluorescence mainly in tubular muscle. Freshly prepared tubular myofibrils decorated with the immunoabsorbed antibody show the A region in the sarcomere as the specific localization of paramyosin. The amount of paramyosin in tubular synchronous muscles of insects appears to be five times higher than in fibrillar insect muscles. There are at least three paramyosin isoforms as shown by isoelectrofocusing separation. The more acidic and less abundant form is phosphorylated as shown by 32P in vivo labeling experiments in adult flies. The developmental pattern of expression of Drosophila paramyosin is presented. This mesoderm-specific protein, immunologically undetectable during gastrulation and early phases of germ band formation, progressively increases during organogenesis to the adult stage. Interestingly, it is also expressed as a major maternal product in the insoluble cytoskeletal fraction of the mature oocyte. PMID- 1908015 TI - Conformation and mobility of the RNA-binding N-terminal part of the intact coat protein of cowpea chlorotic mottle virus. A two-dimensional proton nuclear magnetic resonance study. AB - Two-dimensional proton nuclear magnetic resonance (n.m.r.) experiments were performed on the coat protein of cowpea chlorotic mottle virus (molecular mass: 20.2 kDa) present as dimer (pH 7.5) or as capsid consisting of 180 protein monomers (pH 5.0). The spectra of both dimers and capsids showed resonances originating from the flexible N-terminal region of the protein. The complete resonance assignment of a synthetic pentacosapeptide representing this N terminus made it possible to interpret the spectra in detail. The capsid spectrum showed backbone amide proton resonances arising from the first eight residues having a flexible random coil conformation, and side-chain resonances arising from the first 25 N-terminal amino acids. The dimer spectrum showed also side-chain resonances of residues 26 to 33, which are flexible in the dimer but immobilized in the capsid. The n.m.r. experiments indicated that the conformation of the first 25 amino acids of the protein in dimers and capsids is comparable to the conformation of the synthetic peptide, which alternates among extended and helical conformations on the n.m.r. time-scale. It is suggested that the alpha helical region, situated in the region between residues 10 and 20, binds to the RNA during assembly of the virus particle. PMID- 1908016 TI - The Adh genomic region of Drosophila ambigua: evolutionary trends in different species. AB - The study of individual genes is essential to a comprehensive understanding of genome evolution. The wealth of information on alcohol dehydrogenase (Adh) in Drosophila makes this gene particularly suitable for such analysis. We have characterized more than 4 kb of the genomic Adh region in Drosophila ambigua and compared this region to Drosophila mauritiana and Drosophila pseudoobscura. The presence of two genes, Adh and 3'ORF (open reading frame), has been confirmed and some of their essential features have been inferred from primary structural analysis. Inter- and intraspecific comparisons have led us to support that both genes may have diverged from an ancient precursor. They appear to be evolving independently, and show a species-specific pattern. The Adh in the obscura group species lacks amino acids three and four when compared to the species of the melanogaster group and has accumulated most of its amino acid replacements in the third exon. Neither characteristic is observed when any other group species are compared, which suggests that these may be particular features of the evolution of the obscura group. The 3'ORF is highly conserved among the three species analyzed, although variability in the length of the third exon and the nucleotide substitution rate, which is much higher than in Adh, are worth noting. According to our data, both mutation/fixation rates and the distribution of mutations vary over time, which makes it difficult to predict the evolutionary dynamics of specific genome regions. PMID- 1908017 TI - Evolutionary relations between subtypes of telomere-associated repeats in Chironomus. AB - Telomere-associated DNA in Chironomus pallidivittatus contains tandemly repeated 340-bp units. We show that they are distributed among several subtypes of which we have characterized two, M1 and D1, with regard to base sequence, homogeneity, and intertelomeric distribution. Each subpopulation is highly homogeneous and the two subtypes have identical consensus sequences throughout 90% of their lengths. In the remaining part the homology is only about 60%. Each subpopulation has its specific intertelomeric distribution and there is no difference in the degree of homogenization within and between telomeres. The repeat unit contains two pairs of subrepeats embedded in linker DNA. This provides a model that makes it possible to relate the two subtypes to each other with regard to evolutionary history. The difference between the two subtypes is due to mutations that have occurred in only one of them, D1, resulting in a decreased similarity between one of its pairs of subrepeats. This type of repeat unit is therefore believed to be derived from the other, M1. The local decrease in similarity between M1 and D1 suggests that homogenization between them occurs by gene conversion. PMID- 1908018 TI - Cloning and sequencing of bovine apolipoprotein E complementary DNA and molecular evolution of apolipoproteins E, C-I, and C-II. AB - Apolipoprotein (apo) E, a major protein component of plasma lipoproteins, is a physiological ligand for the low density lipoprotein (LDL) receptor as well as for a specific apoE receptor; it is therefore an important modulator of lipoprotein metabolism. In this study we cloned and sequenced bovine apoE complementary DNA. Comparison of nucleotide substitution rates shows that apoE is less conservative than apoA-I and evolves about 30% faster than an average mammalian protein. Although apoE is not a conservative protein, several regions have been well conserved among all eight mammalian sequences now available. These include a 33-amino-acid block immediately upsteam from the third intron/exon junction and the LDL receptor binding region. We have also compared published apoC-I and apoC-II sequences. Both proteins are less conservative than apoE. In particular, apoC-I shows no well-conserved region except for a small region in the common 33-amino-acid block, suggesting that the function of apoC-I does not have stringent structural requirements. On the other hand, in apoC-II the region encoded by exon 4, which consists of the last 29 amino acids of the polypeptide, has been rather well conserved, probably because this region is important for the activation of lipoprotein lipase and chylomicron and very low density lipoprotein metabolism. PMID- 1908020 TI - The compositional properties of human genes. AB - The present work represents the first attempt to study in greater detail previously proposed compositional correlations in genomes, based on a body of additional data relating to gene localizations as well as to extended flanking sequences extracted from gene banks. We have investigated the correlations that exist between (1) the GC levels of exons of human genes, and (2) the GC levels of either intergenic sequences or introns associated with the genes under consideration. In both cases, linear relationships with slopes close to unity were found. The similarity of the linear relationships indicates similar GC levels in intergenic sequences and introns located in the same isochores. Moreover, both intergenic sequences and introns showed GC levels 5-10% lower than the corresponding exons. The above findings considerably strengthen the previously drawn conclusion that coding and noncoding sequences (both inter- and intragenic) from the same isochores of the human genome are compositionally correlated. In addition, we find linear correlations between the GC levels of codon positions and of the intergenic sequences or introns associated with the corresponding genes, as well as among the GC levels of codon positions of genes. PMID- 1908019 TI - Evolution of the rat kallikrein gene family: gene conversion leads to functional diversity. AB - Kallikrein-like simple serine proteases are encoded by closely related members of a gene family in several mammalian species. Molecular cloning and genomic Southern blot analysis after conventional and pulsed-field gel electrophoresis indicate that the rat kallikrein gene family comprises 15-20 members, probably closely linked at a single locus. Determination of the nucleotide sequences of the rGK-3, -4, and -6 genes here completes sequence data for a total of nine rat kallikrein family members. Comparison of the rat gene sequences to each other and to those of human and mouse kallikrein family genes reveals patterns of relatedness indicative of concerted evolution. Analysis of nucleotide sequence variants in kallikrein family members shows that most sequence variants are shared by multiple family members; the patterns of shared variants are complex and indicate multiple short gene conversions between family members. Sequence exchanges between family members generate novel assortments of variants in amino acid coding regions that may affect substrate specificity and thereby contribute to the diversity of enzyme activity. Furthermore, small sequence exchanges also may play a role in generating the diverse patterns of tissue-specific expression of rat family members. These analyses indicate an important role for gene conversion in the evolution of the functional diversity of these duplicated genes. PMID- 1908021 TI - Correlations between the compositional properties of human genes, codon usage, and amino acid composition of proteins. AB - We have analyzed the correlation that exists between the GC levels of third and first or second codon position for about 1400 human coding sequences. The linear relationship that was found indicates that the large differences in GC level of third codon positions of human genes are paralleled by smaller differences in GC levels of first and second codon positions. Whereas third codon position differences correspond to very large differences in codon usage within the human genome, the first and second codon position differences correspond to smaller, yet very remarkable, differences in the amino acid composition of encoded proteins. Because GC levels of codon positions are linearly correlated with the GC levels of the isochores harboring the corresponding genes, both codon usage and amino acid composition are different for proteins encoded by genes located in isochores of different GC levels. Furthermore, we have also shown that a linear relationship with a unit slope and a correlation coefficient of 0.77 exists between GC levels of introns and exons from the 238 human genes currently available for this analysis. Introns are, however, about 5% lower in GC, on average, than exons from the same genes. PMID- 1908023 TI - Average values of a dissimilarity measure not requiring sequence alignment are twice the averages of conventional mismatch counts requiring sequence alignment for a variety of computer-generated model systems. AB - A measure of sequence similarity, dt, not requiring prior sequence alignment gave correct results for a variety of computer-generated model sequences without and with gaps for all degrees of substitution, s. Measure d was the squared Euclidean distance between vectors of counts of t-tuplets of characters in the two sequences. In models without gaps and without Needleman-Wunsch alignment, average d was very closely equal to twice average conventional mismatch counts, m. In these models one of each of the conditions on the Jukes-Cantor model was violated in turn: (1) both descendant lineages receive the same number of substitutions, (2) all sites are equally likely to be substituted, (3) all different replacement characters are equally likely to be chosen, and (4) all original characters are equally likely to be substituted. In Jukes-Cantor models with gaps Needleman Wunsch alignment was necessarily performed, a procedure that generally produced incorrect values of m. For these models average d was found to be very closely equal to twice the average m estimated from the known value of s using the inverted Jukes-Cantor formula. PMID- 1908022 TI - Strand-specific nucleotide composition bias in echinoderm and vertebrate mitochondrial genomes. AB - The gene organization of starfish mitochondrial DNA is identical with that of the sea urchin counterpart except for a reported inversion of an approximately 4.6-kb segment containing two structural genes for NADH dehydrogenase subunits 1 and 2 (ND 1 and ND 2). When the codon usage of each structural gene in starfish, sea urchin, and vertebrate mitochondrial DNAs is examined, it is striking that codons ending in T and G are preferentially used more for heavy strand-encoded genes, including starfish ND 1 and ND 2, than for light strand-encoded genes, including sea urchin ND 1 and ND 2. On the contrary, codons ending in A and C are preferentially used for the light strand-encoded genes rather than for the heavy strand-encoded ones. Moreover, G-U base pairs are more frequently found in the possible secondary structures of heavy strand-encoded tRNAs than in those of light strand-encoded tRNAs. These observations suggest the existence of a certain constraint operating on mitochondrial genomes from various animal phyla, which results in the accumulation of G and T on one strand, and A and C on the other. PMID- 1908024 TI - Morphology and antibody recognition of synthetic beta-amyloid peptides. AB - To elucidate the relationship between amyloid fibril formation in Alzheimer disease (AD) and the primary structure of the beta-amyloid protein (beta-AP), we investigated the ability of peptides sharing sequences with beta-AP to form fibrils in vitro and to recognize anti-beta-amyloid antisera. The peptides, which were synthesized using a FMOC solid phase procedure and purified by HPLC, consisted of residues 6-25 from the putative aqueous domain, residues 22-35, which overlaps the putative aqueous and transmembrane domains, and residues 1-38 and 1-40 representing nearly the full length of beta-AP. Electron microscopy of negative-stained or thin-sectioned preparations revealed that the peptides assembled into fibrils having different morphologies, some of which resembled in situ AD amyloid. Peptide 6-25 fibrils had diameters of 50-80 A and occasionally showed a central groove suggestive of constituent filaments. Cross sections of the fibril showed a penta- or hexameric arrangement of globular subunits with diameters of 25-30 A. Peptide 22-35 fibrils were helical, with a pitch of 1,100 A and a width of 120 A at its greatest and 50-60 A at its narrowest. The fibrils formed by peptides 1-38 and 1-40 were 70-90 A in diameter. When the peptide assemblies were singly oriented by sedimentation or doubly oriented in a magnetic field, their X-ray diffraction patterns all showed reflections typical of a cross beta pleated sheet conformation. The patterns differed mainly in their small angle equatorial intensity, which arises from the packing of fibrils having different widths. Antiserum raised to either native amyloid or to synthetic peptide beta-(1-28) was highly reactive in an inhibition-ELISA assay to beta-(6 25) and beta-(1-38), but not to beta-(22-35), and immunostained beta-(1-40) on Western blots. These studies show that the beta-(6-25), beta-(1-38) and beta-(1 40) peptides can assemble into cross-beta fibrils that retain epitopes characteristic of AD amyloid. PMID- 1908025 TI - Transfer of 45Ca and 36Cl at the blood-nerve barrier of the sciatic nerve in rats fed low or high calcium diets. AB - Unidirectional fluxes of 45Ca, 36Cl, and of [3H]mannitol from blood into the sciatic nerve and cerebral cortex were determined from 5- and 15-min uptakes of these tracers after an intravenous (i.v.) bolus injection in awake rats. Rats were fed diets for 8 wk, that had either a low (0.01% wt/wt), normal (0.67%), or high (3%) Ca content. Plasma [Ca] was 32% less and 11% more in rats fed low (LOCA) and high Ca diets (HICA), respectively, than in rats fed a normal Ca diet (CONT). The mean permeability-surface area product (PA) of 45Ca at the blood nerve barrier was about eightfold higher than at the blood-brain barrier in the same animals and did not differ significantly between groups (greater than 0.05). Mean PA ratios of 45Ca/36Cl for the blood-nerve and blood-brain barriers in CONT rats, 0.52 +/- 0.04 and 0.40 +/- 0.02, respectively, were not significantly different from corresponding ratios in LOCA and HICA groups, and corresponded to the aqueous limiting diffusion ratio (0.45). Our results show no evidence for concentration-dependent transport of Ca over a plasma [Ca] range of 0.8-1.4 mmol/liter at the blood-nerve barrier of the rat peripheral nerve, and suggest that Ca and Cl exchange slowly between nerve and blood via paracellular pathways. PMID- 1908026 TI - The management of otolaryngological problems in the mucopolysaccharidoses: a retrospective review. AB - The mucopolysaccharidoses are rare, genetically transmitted metabolic disorders that affect children early in life. These potentially life-threatening diseases almost invariably involve the auditory apparatus and the upper respiratory tract. Thus, the otolaryngologist is frequently involved in the care of these patients. This paper presents a 10-year retrospective review of the management of these patients at the Hospital for Sick Children. Data concerning auditory and upper respiratory pathology are presented. Results indicate that persistent serous otitis, sensorineural hearing loss, and upper respiratory obstruction leading to sleep apnea, are frequent findings in these patients. Specific recommendations are made with regard to appropriate otolaryngologic intervention in children affected with these diseases. PMID- 1908027 TI - Molecular cloning and characterization of a complete Chinese hamster provirus related to intracisternal A particle genomes. AB - We report here the nucleotide sequence of a full-length Chinese hamster genomic proviral element, CHIAP34. CHIAP34 is 6,403 bp long with long terminal repeats of 311 bp at each end. The genetic organization of CHIAP34 was determined by comparison with intracisternal A particle (IAP) genetic elements from the mouse and Syrian hamster. Extensive homology at the nucleotide and deduced amino acid sequence levels was observed between CHIAP34 and the mouse and Syrian hamster IAP elements. CHIAP34 may represent a defective Chinese hamster IAP genetic element. The gag gene consists of 837 codons, of which 558 codons are in a single long open reading frame followed by several frameshifts. The pol gene begins with a -1 frameshift and consists of a long open reading frame of 753 codons followed by a short open reading frame of 103 codons. The putative env region contains multiple termination codons in all reading frames. CHIAP34 is representative of the predominant retroviral elements in the Chinese hamster ovary cell genome present at around 80 copies per haploid genome. PMID- 1908028 TI - Respiratory syncytial virus infection in anti-mu-treated mice. AB - BALB/c mice were depleted of B cells by anti-mu treatment to investigate the pathogenesis of respiratory syncytial virus (RSV) infection in the absence of antibody. Termination of RSV replication after primary infection occurred with the same kinetics in anti-mu-treated mice as in phosphate-buffered saline (PBS) treated controls. Yet, when rechallenged, anti-mu-treated mice were more permissive to RSV replication than PBS-treated controls. Anti-mu-treated mice also experienced greater illness than PBS-treated controls during both primary infection and rechallenge. Passive transfer of RSV-specific immune serum to anti mu-treated mice before rechallenge reconstituted complete protection from RSV replication and diminished illness. Thus, RSV-specific antibody is not required to terminate RSV replication in primary infection, but without antibody, only partial immunity against rechallenge is induced. While it is unknown whether the mechanism is a direct effect on RSV titer or modulation of the illness-causing cellular immune response, the presence of RSV-specific antibody reduces illness in both primary RSV infection and rechallenge of mice. PMID- 1908031 TI - Pharmacological manipulation of gastrocnemius muscle blood flow in an animal model of reperfusion injury. AB - Despite technically satisfactory surgery for acute lower limb ischaemia reperfusion injury may result in failure of limb salvage and the need for amputation. An animal model using the rat hind limb has been developed which demonstrates this complication. A tourniquet was applied to one hind limb for 6 h and then released. Gastrocnemius muscle blood flow in both hind limbs was assessed using radiolabelled microspheres and a perfusion index calculated between the revascularized and normal hind limbs and the results compared with similar measurements in control animals and rats with a tourniquet still in situ (ischaemic). Following 10 min the median perfusion index in reperfused animals was significantly less than that in control animals (0.12 +/- 2 inter-quartile range 0.02-0.43) versus 1.05 (0.68-1.18), P less than 0.01) but similar to the results in rats with a tourniquet still in situ [0.04 (0.00-0.07), ns], thus demonstrating low reflow following tourniquet release. After 120 min revascularization a phase of relative reperfusion occurred with perfusion indices becoming higher than those in animals with a tourniquet in situ (0.48 (0.11-0.70) versus 0.02 (0.01-0.07), P less than 0.05) but remaining lower than those in control rats [0.97 (0.79-1.13), P less than 0.05]. Finally after 240 min, reperfusion injury occurred with perfusion being similar to that in animals with a tourniquet applied [0.05 [0.01-0.38) versus 0.03 (0.00-0.07), ns] and less than that in the normal rats [1.01 (0.73-1.16), P less than 0.01].(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1908030 TI - Unsuspected osteomyelitis in diabetic foot ulcers. Diagnosis and monitoring by leukocyte scanning with indium in 111 oxyquinoline. AB - OBJECTIVE: The prevalence of osteomyelitis in diabetic foot ulcers is unknown. Early diagnosis of this infection is critical, as prompt antibiotic treatment decreases the rate of amputation. We therefore assessed the prevalence of osteomyelitis in 35 diabetic patients with 41 foot ulcers. We compared results of roentgenograms, leukocyte scans with indium In 111 oxyquinoline, and bone scans with the diagnostic criterion standards of bone histologic and culture findings. Leukocyte scans were repeated at 2- to 3-week intervals during antibiotic treatment. DESIGN: Cohort study. SETTING: Institutional and private, ambulatory and hospitalized patients. PATIENTS: Consecutive sample of 54 diabetic patients. Thirty-five patients with 41 foot ulcers were included. RESULTS: As determined by bone biopsy and culture, osteomyelitis was found to underlie 28 (68%) of 41 diabetic foot ulcers. Only nine (32%) of the 28 cases were diagnosed clinically by the referring physician. Underscoring the clinically silent nature of osteomyelitis in these ulcers, 19 (68%) of 28 occurred in outpatients, 19 (68%) of 28 occurred in ulcers not exposing bone, and 18 (64%) of 28 had no evidence of inflammation on physical examination. All patients with ulcers that exposed bone had osteomyelitis. Of the imaging tests, the leukocyte scan had the highest sensitivity, 89%. In patients with osteomyelitis, the leukocyte scan image intensity decreased by 16 to 34 days of antibiotic treatment and normalized by 36 to 54 days. CONCLUSION: The majority of diabetic foot ulcers have an underlying osteomyelitis that is clinically unsuspected. Leukocyte scans are highly sensitive for diagnosing osteomyelitis in diabetic foot ulcers and may be useful for monitoring the efficacy of antibiotic treatment. We recommend that diabetic patients with foot ulcers that expose bone should be treated for osteomyelitis. Diabetic patients with foot ulcers that do not expose bone should undergo leukocyte scanning, which eliminates the risk of bone biopsy in diagnosing osteomyelitis and allows for the diagnosis and treatment of this well-known but often silent precursor of lower extremity amputation. PMID- 1908029 TI - In vivo activation of human immunodeficiency virus type 1 long terminal repeat by UV type A (UV-A) light plus psoralen and UV-B light in the skin of transgenic mice. AB - UV irradiation has been shown to activate the human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) in cell culture; however, only limited studies have been described in vivo. UV light has been categorized as UV-A (400 to 315 nm), -B (315 to 280 nm), or -C (less than 280 nm); the longer wavelengths are less harmful but more penetrative. Highly penetrative UV-A radiation constitutes the vast majority of UV sunlight reaching the earth's surface but is normally harmless. UV-B irradiation is more harmful but less prevalent than UV-A. In this report, the HIV-1 LTR-luciferase gene in the skin of transgenic mice was markedly activated when exposed to UV-B irradiation. The LTR in the skin of transgenic mice pretreated topically with a photosensitizing agent (psoralen) was also activated to similar levels when exposed to UV-A light. A 2-h exposure to sunlight activated the LTR in skin treated with psoralen, whereas the LTR in skin not treated with psoralen was activated after 7 h of sunlight exposure. The HIV-1 LTR-beta-galactosidase reporter gene was preferentially activated by UV-B irradiation in a small population of epidermal cells. The transgenic mouse models carrying HIV-1 LTR-luciferase and LTR-beta-galactosidase reporter genes have been used to demonstrate the in vivo UV-induced activation of the LTR and might be used to evaluate other environmental factors or pharmacologic substances that might potentially activate the HIV-1 LTR in vivo. PMID- 1908033 TI - Leprosy and acquired factor VIII inhibitor: a case report. PMID- 1908032 TI - Possible role of acrolein in 4-hydroperoxycyclophosphamide-induced cell damage in vitro. AB - Unlike "conventional" oxazaphosphorines such as cyclophosphamide (CP) and ifosfamide, a relatively new drug termed 4-hydroperoxy-CP (4-HC) degrades spontaneously in water yielding phosphoramide mustard considered to be the activated cytotoxic metabolite. During this degradation a toxic, volatile factor termed acrolein is also formed. In order to examine the possible role of this compound in 4-HC-induced inhibition of tumor cell growth in vitro, 8 different established human tumor cell lines were cultured in the presence of 4-HC or equimolar concentrations of acrolein. It was observed that the cell lines differed widely with respect to sensitivity to these compounds. However, each individual cell line exhibited virtually identical sensitivities to both 4-HC and acrolein. The observation that 2-mercaptoethansulfonate (mesna), which is highly reactive with acrolein but not with phosphoramide mustard, could markedly reduce the cytotoxic activity of 4-HC indicates that acrolein may play an important role in 4-HC induced cell damage in vitro. PMID- 1908034 TI - Serum ferritin concentration in subacute thyroiditis. AB - Serum concentration of ferritin was measured in 20 patients (19 women, one man) with untreated (thyrotoxic phase) subacute thyroiditis, 32 patients (21 women, 11 men) with untreated Graves' disease, 17 patients (all women) with euthyroid Hashimoto's thyroiditis, 12 patients (all women) with hepatitis A (HAV), eight patients (all women) with pneumonia, and 59 normal controls (30 women, 29 men). In female patients with subacute thyroiditis, the serum concentration of ferritin was 163.6 +/- 116.3 micrograms/L (after log transformation, 2.12 +/- 0.31 micrograms/L, mean +/- SD), which was significantly higher than values in female Graves' disease (P less than .05), Hashimoto's thyroiditis (P less than .001), pneumonia (P less than .05), and healthy subjects (P less than .001), being 97.9 +/- 71.9 micrograms/L (after log transformation, 1.85 +/- 0.42 micrograms/L), 51.6 +/- 53.0 micrograms/L (after log transformation, 1.48 +/- 0.50 micrograms/L), 88.2 +/- 56.3 micrograms/L (after log transformation, 1.86 +/- 0.30 micrograms/L), and 25.2 +/- 7.4 micrograms/L (after log transformation; 1.16 +/- 0.10 micrograms/L), respectively, but was not significantly different with HAV, being 368.3 +/- 514.0 micrograms/L (after log transformation, 2.32 +/- 0.47 micrograms/L). In a male with subacute thyroiditis, the serum concentration of ferritin was 521.8 micrograms/L (after log transformation, 2.72 micrograms/L), which was higher than +/- 3 SD and +/- 1 SD of the levels in healthy males (93.0 +/- 55.9 micrograms/L; after log transformation, 1.89 +/- 0.27 micrograms/L) and male Graves' disease patients (257.0 +/- 195.5 micrograms/L; after log transformation, 2.28 +/- 0.38 micrograms/L), respectively. Elevated serum ferritin concentration significantly declined with treatment by either aspirin or prednisolone (paired t test, P less than .001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1908035 TI - Effects of exercise and ethanol ingestion on platelet thromboxane release in healthy men. AB - We studied the effects of repeated bicycle exercises and ethanol ingestion (1.5 g/kg) on platelet aggregation and thromboxane (TxB2) release in 10 healthy male volunteers. After a bicycle exercise performed in the morning, the adenosine diphosphate (ADP)-induced platelet aggregation and the aggregation-associated thromboxane release were found to be decreased in fasting men. In contrast, after ingestion of fruit juice and a second exercise at noon, platelet aggregation and thromboxane release were increased. These latter changes were negligible when ethanol was ingested together with fruit juice. A third exercise, performed in the evening, again caused a decrease in the aggregation and associated thromboxane release during the control session, but provoked an increase during the ethanol session. Exercise increased the urinary excretion of 2,3-dinor-6-keto PGF1 alpha. Changes in the plasma arachidonic acid (AA) concentration probably influenced the platelet thromboxane release. The results suggest that both physical exercise and ingestion of ethanol in fruit juice influence the ADP stimulated platelet thromboxane release. PMID- 1908036 TI - Combined treatment with chenodeoxycholic acid and pravastatin improves plasma cholestanol levels associated with marked regression of tendon xanthomas in cerebrotendinous xanthomatosis. AB - We studied the effect of chenodeoxycholic acid (CDCA) and a competitive HMG-CoA reductase inhibitor, pravastatin, on clinical symptoms and sterol metabolism in a 36-year-old Japanese man with cerebrotendinous xanthomatosis (CTX). He had marked tendon xanthomas and mild dementia, with obvious electroencephalographic (EEG) abnormalities. He was treated for 2 years with CDCA alone (0.6 g/d) and then for a further year with the combination of pravastatin (10 mg/d) and CDCA (0.6 g/d). For the following year, he was given pravastatin alone, and then was returned to combined treatment again. The plasma cholestanol level before treatment was 3.12 mg/dL, which was 20 times above the control level. After CDCA alone, the plasma cholestanol was reduced to 1.96 mg/dL, and this was further reduced to 0.92 mg/dL by combination therapy with CDCA and pravastatin. However, after the discontinuation of CDCA, his cholestanol levels returned to the pretreatment levels despite the continuing of pravastatin treatment. When the combination therapy was restarted, his cholestanol level was once again markedly reduced. His clinical symptoms showed a close association with the plasma cholestanol level; the xanthomas regressed remarkably and the mental retardation improved in association with normalization of EEG findings during treatment with CDCA alone or in combination with pravastatin. However, during treatment with pravastatin alone, his tendon xanthomas enlarged again and slow waves reappeared on the EEG. Because inhibition of cholesterol synthesis by treatment with the HMG-CoA reductase inhibitor alone was not effective in causing a reduction of cholestanol, the increase in plasma cholestanol levels in CTX may not have been solely due to increased cholesterol synthesis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1908037 TI - The adhesion of protein A-bearing Staphylococcus aureus organisms to soluble staphylococcal-antigens-coated HeLa cells mediated by specific antibodies. AB - The adhesion of staphylococcal protein A (SpA)-bearing Staphylococcus aureus Cowan I organisms to HeLa cells was enhanced by pretreatment of HeLa cells with staphylococcal extracellular antigens and antibodies to them. The adhesion of HLj, an SpA-poor mutant derived from Cowan I, to HeLa cells was not enhanced by the same pretreatment of HeLa cells. Furthermore, the enhanced staphylococcal adhesion was inhibited by soluble SpA. The antigen(s) responsible for the enhanced staphylococcal adhesion was(were) heat stable. Pretreatment of HeLa cells with the mixture of staphylococcal extracellular antigens and antibodies to them also enhanced the adhesion of Cowan I. Similarly the adhesion of Cowan I was enhanced by pretreatment of HeLa cells with extracellular antigens of Pseudomonas aeruginosa and antibodies to them. These results indicated that cell-bound SpA mediated the binding of S. aureus to immune complexes composed of extracellular bacterial products and antibodies to them bound to the surface of HeLa cells, and suggested another role of cell-bound SpA as a co-adhesin with other factors in infections due to S. aureus. PMID- 1908039 TI - Demonstration and characterization of the cell wall carbohydrate and protein antigens from Clostridium botulinum type E Saroma. AB - Two different cell wall antigens, carbohydrate (CHO) and protein (P), from Clostridium botulinum type E Saroma were extracted with sodium dodecyl sulfate (SDS) and purified by chromatography on DEAE-Sepharose CL-6B and Sephadex G-75 or G-100. The CHO antigen was composed of glucose, galactose, glucosamine, galactosamine, alanine and phosphorus with a molar ratio of 1.5:1.5:0.25:0.25:1:1. The P antigen was an acidic protein with a molecular weight of 60 kDa, in which the major amino acids were aspartate, glutamate and serine, while the minor ones were cysteine and methionine. Thin sections of the intact or SDS-extracted cells of the organism demonstrated that the cell wall was composed of a two-layered structure, an inner layer about 20 nm thick and an outer layer about 10 nm, and by the extraction with SDS, the outer layer disappeared from the cell surface, leaving the inner layer. Immunogel diffusion tests demonstrated that either CHO antigen or P antigen was common among the nonproteolytic strains of C. botulinum. PMID- 1908038 TI - Platelet aggregation induced by strains of various species of coagulase-negative staphylococci. AB - Major species of coagulase-negative staphylococci (CNS) were tested for their ability to induce platelet aggregation in rabbit platelet-rich plasma (PRP). Among 11 species of CNS tested, a majority of the strains of 10 species of CNS (S. epidermidis, S. simulans, S. capitis, S. hyicus, S. sciuri, S. cohnii, S. xylosus, S. hominis, S. haemolyticus, S. warneri) caused induction of the platelet aggregation and serotonin release, while S. saprophyticus did not show such activity. The addition of aspirin (10 mM) or quinacrine (1 mM) to PRP resulted in no remarkable effect on the platelet aggregation induced by these strains and it was shown that the platelet aggregation did not require arachidonate pathways. Complement system components were shown to be one of the plasma factors required for platelet aggregation by ten strains of each species of CNS. The bacterial substance participating in the platelet aggregation by ten species of CNS tested was indicated to be heat-stable and trypsin-resistant, while the activity of a strain of S. epidermidis was susceptible to trypsin. PMID- 1908040 TI - Comparative characterization of inducible and virulent Vibrio parahaemolyticus bacteriophages having unique head projections. AB - Phage TP1, induced from Vibrio parahaemolyticus K-20 pilot strain by mitomycin C, exhibited a unique hexagonal head with knob-like projections which covered the whole capsid and a noncontractile tail. The appearance of this phage was very similar to those of phages VP3 and VP6, isolated from seawater. The host range of phage TP1 was similar to those of phages VP3 and VP6. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) of the three phage particles revealed almost identical patterns with four major polypeptides with apparent approximate molecular masses: 78, 42, 37 and 34.5 kDa. On the basis of HindIII digestion patterns on agarose gel electrophoresis, the lengths of phage TP1 and VP3 DNAs were estimated to be about 65 kilobase pairs (kbp) and that of VP6 DNA was about 74 kbp. The digestion patterns of all three phage DNAs by DraI, BamHI and MspI were very similar. The DNAs of TP1 and VP3 exhibited almost the same digestion patterns with HindIII and EcoRI, whereas the digestion patterns of VP6 DNA were significantly different from those of the former. From these findings, it seems likely that virulent phage VP3 is originated from a lysogenic phage, probably TP1, of V. parahaemolyticus. PMID- 1908041 TI - Susceptibility of newly established mouse strain MPS to Mycoplasma pneumoniae infection. AB - A newly established mouse strain, MPS, which is more sensitive to Mycoplasma pulmonis than ICR, ddY and other mouse strains was examined for its susceptibility to Mycoplasma pneumoniae. In experimental infections with M. pneumoniae, it was observed that M. pneumoniae attached to tracheas of MPS mice, and M. pneumoniae cells were isolated from tracheas and lungs of MPS mice even after four weeks of infection, while no mycoplasmas were isolated from ICR and ddY mice after one week of infection. Specific antibodies against M. pneumoniae were also observed by the Western blotting in the sera of MPS mice infected with M. pneumoniae. Although any lung lesion could not be observed in this work, this newly established mouse strain MPS may be useful for experiments of M. pneumoniae infection, especially for the analysis of strain differences in susceptibility to M. pneumoniae infection. PMID- 1908042 TI - Analysis of the tdh gene cloned from a tdh gene- and trh gene-positive strain of Vibrio parahaemolyticus. AB - A variant of the gene (tdh) encoding thermostable direct hemolysin (TDH) was cloned from the chromosome of Vibrio parahaemolyticus AQ3860, which gave positive results in the hybridization tests with the tdh gene probe and the trh (tdh related hemolysin) gene probe and showed a low level of reaction in an enzyme linked immunosorbent assay for TDH. Nucleotide sequence analysis of the cloned gene (tdh5) provided no evidence that tdh5 is evolutionally closer to the trh gene than the other tdh genes. The tdh5 gene was flanked by 40 base-pair sequences constituting perfect inverted repeats, which may suggest association of the tdh5 gene with insertion sequence-like structure. These results suggest that the tdh5 gene and the trh gene were not originally produced by gene duplication in AQ3860 but rather that one of the two genes moved into AQ3860 from an external source. PMID- 1908043 TI - [Personal experience in the immunomodulation of immunothrombocytopenic purpura in children using high doses of i.v. immunoglobulin]. AB - Twenty-three child patients with immunothrombocytopenic purpura ITP were treated with high doses of immunoglobulins for intravenous application. The dose applied was 400 mg/kg during five consecutive days. The immunological status of all patients was determined previously, and beside the normal values of the IgG serum, a deficit of the IgG2 subclass was discovered in 12 patients. The therapy effect was satisfactory in 19 patients, and 4 had an absence of a satisfactory response to therapy. There was an interesting observation that all patients with a good response to therapy had a deficit of the IgG2 subclass, while with all the other patients without a satisfactory response to therapy the, IgG2 subclass had normal values. On the basis of the results observed it can be concluded that i.v. immunoglobin therapy in high doses has it's place in the immunothrombocytopenia treatment of children, and especially of patients with an IgG2 subclass deficit. PMID- 1908044 TI - Rotational kernels for conformal therapy. AB - Conformal therapy treatment planning involves determining an irradiation strategy to deliver a dose distribution which is optimized for a given tumor volume. A technique proposed by Brahme restricts the search for the optimal treatment strategy to x-ray distributions in which points within the target volume are irradiated uniformly under rotation of the beam source around the patient. The dose distribution in this case may be calculated as a convolution of an irradiation weighting distribution with an invariant kernel. A procedure is described for calculating three-dimensional kernels to be used for clinical treatment planning with x rays produced by an electron accelerator. The convolution kernel is calculated as the sum of pencil beams irradiating the center of a cylindrical phantom uniformly from all angles. The shape of the kernel at points off the center of the phantom is investigated by means of numerical calculations which support the assumption that the kernel is invariant with respect to position within the phantom. The calculated kernels are verified by comparison with experimentally measured rotational arc dose distributions. PMID- 1908045 TI - Sensitivity of helium beam-modulator design to uncertainties in biological data. AB - The goal in designing beam-modulating devices for heavy charged-particle therapy is to achieve uniform biological effects across the spread-peak region of the beam. To accomplish this, the linear-quadratic model for cell survival has been used to describe the biological response of the target cells to charged-particle radiation. In this paper, the sensitivity of the beam-modulator design in the high-dose region to the values of the linear-quadratic variables alpha and beta has been investigated for a 215-MeV/u helium beam, and implications for higher LET beams are discussed. The major conclusions of this work are that, for helium over the LET range of 2 to 16 keV/mu, uncertainties in measuring alpha and beta for a given cell type which are of the order of 20% or less have a negligible effect on the beam-modulator design (i.e., on the slope of the spread Bragg peak); uncertainties less than or equal to 10% in the dose-averaged LET at each depth are unimportant; and, if the linear-quadratic variables for the tumor differ from those used in the beam-modulator design by a constant factor between about 0.5 and 3, then the resultant nonuniformity in the photon-equivalent dose delivered to the tumor is within +/- 25%. It is also shown that for any ion, if the nominal values of alpha or beta used by the beam-modulator design program differ from their actual values by a constant factor, then the maximum errors possible in the beam-modulator design may be characterized by two limiting depth dose curves such that the ratio of the dose at the proximal end of the spread Bragg curve to the dose at the distal end of the spread peak is given by alpha distal/alpha prox for the steepest curve, and square root of beta distal/beta prox for the flattest curve. PMID- 1908046 TI - Design of beam-modulating devices for charged-particle therapy. AB - The computer modeling program used to design beam-modulating devices for charged particle therapy at Lawrence Berkeley Laboratory has been improved to allow a more realistic description of the beam. The original program used a single calculated Bragg peak to design the spread Bragg peak. The range of this curve was shifted so that Bragg curves of varying ranges could be superimposed. The new version of the program allows several measured Bragg curves with different ranges to be used as input, and interpolates between them to obtain the required data for the superposition calculation. The experimental configuration for measuring these input curves simulated therapy conditions. Seven beam-modulating propellers with spread Bragg-peak widths ranging from 2.2 to 14.4 cm were designed and constructed for a 215-MeV/u helium beam using this new design program. Depth-dose distributions produced by these new propellers were in good agreement with predicted distributions, and these propellers are currently being used clinically. PMID- 1908047 TI - Radiosurgery with unflattened 6-MV photon beams. AB - One of the major drawbacks to doing stereotactic radiosurgery with a linear accelerator is the long time required to deliver the target dose. Single fractions of 25 Gy delivered at the isocenter and at depth in the skull may require beam times in excess of 15 min for a typical linear accelerator with a maximum dose rate of 250 cGy/min in tissue. In an effort to decrease the treatment time for this technique, the flattening filter has been removed from an AECL Therac-6 linear accelerator and the characteristics of the resulting beam have been measured. Flatness is acceptable for the field sizes used with this technique and the dose rate is increased by a factor of 2.75. PMID- 1908049 TI - [Congenital hemiplegia and epilepsy. The significance of disorders of the cortical architectonics]. PMID- 1908048 TI - Semianalytical expressions for (L/rho)(air)med and P(repl) for electron beams. AB - The tables of the mean restricted collision mass stopping power ratios for water, polystyrene and acrylic relative to air given in the AAPM TG-21 protocol have been fitted to an expression with 20 coefficients using the depth in the phantom and the mean incident electron energy as two independent variables. Using these expressions, the calculated values agree with the tabulated values within +0.5% in 85% of the cases and within +/- 1.0% in 95% of the cases. For each of the four cylindrical chamber inner diameters, given in the protocol, the electron fluence correction Prepl has been fitted to an expression with four coefficients using the mean electron energy at depth z as an independent variable. PMID- 1908050 TI - [Encephalopathies with neonatal onset and suppression-burst type EEG pattern]. PMID- 1908051 TI - Differentiation of Mycobacterium tuberculosis and Mycobacterium bovis BCG by a polymerase chain reaction assay. AB - Mycobacterium tuberculosis and Mycobacterium bovis are closely related species which carry different numbers of the repetitive DNA element IS6110. A polymerase chain reaction assay was developed to assess the copy number of IS6110 in a strain and thereby differentiate these two important human pathogens. PMID- 1908052 TI - In vitro and in vivo analysis of somatic and germline mutability of 2-amino-N6 hydroxyadenine in Drosophila melanogaster. AB - Two complementary assays were employed to examine the mutagenicity of 2-amino-N6 hydroxyadenine (AHA) in Drosophila melanogaster. A lambda phage-based shuttle vector system, utilizing the supF transfer RNA gene of Escherichia coli, questioned the mutagenicity of AHA in established cell cultures derived from somatic tissue while the standard sex-linked recessive lethal assay measured mutational events in vivo. Consistent with studies in other systems, AHA appears strongly mutagenic when cells are exposed directly. Conversely, in vivo studies suggest that AHA is not a strong mutagen. Further studies will determine if AHA is weakly or not mutagenic in vivo and, using the supF system, what the nature of the mutational events at the molecular level is. PMID- 1908053 TI - The mutagenicity of 2-amino-N6-hydroxyadenine to L5178Y tk +/- 3.7.2C mouse lymphoma cells: measurement of mutations to ouabain, 6-thioguanine and trifluorothymidine resistance, and the induction of micronuclei. AB - 2-Amino-N6-hydroxyadenine (AHA) was tested in the mouse lymphoma L5178Y tk +/- assay using the microtitre cloning technique over concentrations from 0.005 micrograms/ml-1 (100% viability) to 6 micrograms/ml (10% viability) as measured by cloning efficiency immediately after treatment. At low, non-toxic concentrations (0.005-0.25 micrograms/ml) a dose-related linear increase in the frequency of ouabain-resistant mutants was seen, in addition to an increase in 6 thioguanine- and trifluorothymidine-resistant mutants. No consistent induction of micronucleated cells was observed in this concentration range. Toxic concentrations (20-90% kill) induced a dose-related increase in micronuclei, while the frequency of ouabain-resistant mutants fell (although it was still highly significantly above the control value). These results suggest that the mechanism of action of AHA depends on the concentration, with point mutations being induced at low, non-toxic doses and detectable chromosome breakage occurring only at higher doses. Both large-colony and small-colony trifluorothymidine-resistant mutants were induced at all concentrations. The utility of using multiple genetic end-points in one cell line and the importance of dose range selection for risk assessment and an understanding of the mode of action of test substances is underlined. PMID- 1908054 TI - Acrolein genotoxicity in Drosophila melanogaster. I. Somatic and germinal mutagenesis under proficient repair conditions. AB - The genotoxicity of acrolein in D. melanogaster was investigated using 2 different SMART assays, the eye spot and wing spot tests, and 2 germinal tests, the sex-linked recessive lethal (SLRLT) and sex chromosome loss (SCLT) tests. For the 2 latter, exposure by feeding as well as injection was used. The results indicate that: (i) acrolein is mutagenic in the SLRLT when injected but not when fed; (ii) the SCLT did not reveal clastogenic effects; (iii) acrolein had genotoxic effects in both SMART assays; (iv) we also had several indications that acrolein is metabolized into a second genotoxic product. PMID- 1908055 TI - Report of a comparative study of DNA damage and repair assays in primary rat hepatocytes with five coded chemicals. AB - We report the results of a collaborative study for the detection of chemical induced DNA damage in primary cultures of rat hepatocytes. The methods include the detection of unscheduled DNA synthesis (UDS) with either autoradiography (5 laboratories) or liquid scintillation counting (2 laboratories) and the assessment of DNA single-strand breaks with the alkaline elution assay (1 laboratory). Interlaboratory standardization was omitted in order to prove the agreement of the assays under routine conditions. Five coded chemicals were tested. For 4 chemicals (2-acetylaminofluorene, thiourea, glycerine and potassium chloride) the UDS data were consistent in all laboratories, thus indicating a high consensus of the test systems applied in the different laboratories. Those 3 chemicals that were not expected to elicit genotoxic activity (thiourea, glycerine, and potassium chloride) yielded negative results in all laboratories. 2-Acetylaminofluorene, a known DNA-damaging agent in hepatocytes, gave strongly positive responses in all laboratories. In contrast, N-nitrosodiphenylamine led to equivocal responses. PMID- 1908056 TI - Stability of tk-/- mutants of L5178Y mouse lymphoma cells in Fischer's medium. AB - The phenotypic stability of over 2000 large- and small-colony trifluorothymidine resistant (TFTres) variants of L5178Y/tk(+/-)-3.7.2C cells has been examined. All except 4 of 488 spontaneously arising small-colony variants analyzed (0.8%) retained the TFTres phenotype when rechallenged with TFT after growth for several generations in its absence. All of 558 spontaneous large-colony variants, and 440 small-colony or 487 large-colony variants arising from 13 different mutagens showed similar stability. These results attest to the completeness of TFT selection in the mouse-lymphoma assay when used at 1 microgram/ml in Fischer's medium supplemented with heat-inactivated serum and, together with previous cytogenetic and molecular studies, justify considering essentially all such TFTres variants as stable mutants. The implications of these results for those versions of the mouse lymphoma assay that fail to optimize the recovery and scoring of small-colony mutants is discussed. PMID- 1908058 TI - Catabolic illness. Strategies for enhancing recovery. AB - After injury, infection, extensive chemotherapy, and other critical illnesses, both protein and fat are lost from the body. Although minor alterations in body composition are probably of little clinical importance, losses of body protein of 10 percent or more contribute to morbidity and debility. This catabolic response can be modified and recovery can be accelerated by a variety of approaches. First, the inflammatory response can be reduced; second, specific nutrients can be provided to support the patient's tissue requirements during catabolic illness; and third, growth factors can be used to enhance protein synthesis and tissue repair. These approaches, whether used alone or in combination, will reduce the loss of body protein, which should accelerate recovery, shorten the length of hospitalization, and reduce convalescence. PMID- 1908057 TI - X-linked recessive nephrolithiasis with renal failure. AB - BACKGROUND AND METHODS: Nephrolithiasis may occur as a consequence of a number of hereditary disorders. We describe a large kindred from northern New York with hereditary nephrolithiasis accompanied by urinary concentrating defects, nephrocalcinosis, renal insufficiency, and renal wasting of potassium, phosphate, calcium, and uric acid. The pattern of inheritance was established by examining the patients and their records and interviewing family members. Selected members of the family were evaluated in detail, with measurements of erythrocyte cation fluxes and carbonic anhydrase (carbonate dehydratase) activity. RESULTS: The kindred consisted of 162 family members from six generations. All nine affected persons were male and appeared to have inherited the disease from their mothers. No affected man transmitted the gene to a son, but the daughters of affected men were carriers. The patients presented in childhood with calcium nephrolithiasis and proteinuria, with progression to nephrocalcinosis, urinary concentrating defects, and renal insufficiency. Renal biopsies revealed tubular atrophy, interstitial fibrosis, and glomerulosclerosis; the characteristic features of other forms of hereditary nephritis were absent. Abnormalities in the renal excretion of calcium, phosphate, potassium, and uric acid were found only in the adult members of the kindred, although renal biopsies were abnormal even in younger members. In one patient who has had a renal transplant for seven years, the disease has not recurred. CONCLUSIONS: This kindred manifested an X-linked recessive nephrolithiasis with renal failure, a new form of hereditary renal disease. Most of the identifiable physiologic abnormalities occurred after the development of nephrolithiasis and renal insufficiency and may not be of pathogenetic importance. PMID- 1908059 TI - Inhaled pentamidine and prevention of Pneumocystis pneumonia. PMID- 1908060 TI - Failure of prophylaxis with dapsone in patients taking dideoxyinosine. PMID- 1908061 TI - Feedback of follicle-stimulating hormone to inhibit luteinizing hormone and stimulate follicle-stimulating hormone release in ovariectomized rats. AB - Injection of ovine follicle-stimulating hormone (o-FSH) into the third cerebral ventricle significantly suppressed plasma luteinizing hormone (LH) release in conscious, unrestrained ovariectomized rats. Intraventricular injection of o-FSH (0.5 microgram) significantly lowered the plasma levels of LH by 70 min and decreased pulse frequency, whereas the pulsatile release of FSH was unchanged during the 180-min duration of the experiment. In a 12-hour experiment, the suppression of LH release reached the maximum within 3 h (p less than 0.001), followed by a return of plasma LH level to initial values 6-8 h after intraventricular injection of o-FSH at doses of 0.5, 4 and 8 micrograms. Plasma levels of FSH were not significantly changed by the low dose of o-FSH (0.5 microgram), but there was a delayed elevation of plasma FSH during the 8-12 h after intraventricular injection of o-FSH at higher doses (4 and 8 micrograms). On the other hand, plasma prolactin was unchanged after intraventricular injection of o-FSH. Since the pituitary responsiveness to synthetic LH-releasing hormone (LHRH) was unimpaired at the end of the sampling and incubation with o FSH suppressed the release of LHRH from median eminence terminals, these data indicate that FSH acts intrahypothalamically to suppress LHRH release. The late elevation of plasma FSH may be the result of enhanced release of FSH-releasing factor or of a delayed, direct effect of the hormone on the gonadotropes to increase release of FSH.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1908062 TI - Studies of growth hormone secretion in calorically restricted dogs: effect of cholinergic agonists and antagonists, glucose and thyrotropin-releasing hormone. AB - The effect of caloric restriction (CR) on the growth hormone (GH) response to compounds reportedly capable of acting via somatostatinergic influences, i.e. cholinergic agonist or antagonist drug, glucose or thyrotropin-releasing hormone (TRH), administered alone or combined with GH-releasing hormone (GHRH), was evaluated in dogs. Eight beagle dogs, aged 4-5 years, underwent a 26-day period of increasing CR; they were evaluated either under basal conditions or starting from day 13 of CR, according to a schedule which allowed the mean length of CR to be similar among individual tests. CR resulted in a significant increase in basal GH levels, and starting from day 13 in a significant decrease in plasma somatomedin C levels; plasma glucose levels were significantly diminished on day 13 of CR and then remained unaltered. Administration of GHRH (GHRH1-44, 2 micrograms/kg, i.v.) induced a rise in plasma GH levels strikingly higher during CR than under basal conditions. Pyridostigmine (2 mg/kg orally), a muscarinic cholinergic agonist reportedly capable of restraining hypothalamic release of somatostatin (SS), enhanced the GH response to GHRH under basal conditions, but failed to do so during CR. Conversely, pirenzepine (0.6 mg/kg, i.v.), a muscarinic cholinergic antagonist, abolished the GHRH-induced GH rise under basal conditions, but only reduced it during CR. Only by doubling the dose of pirenzepine was complete inhibition of the GHRH-induced GH rise effected. Glucose alone (2 g/kg, p.o.) failed to modify basal GH secretion either before or during CR, but significantly inhibited the GHRH-induced GH rise either before or during CR.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1908063 TI - Ossified mucin-secreting choroid plexus adenoma: case report. AB - This is the first report of a fully documented case of an ossified mucin producing benign choroid plexus tumor. This was a chance finding in a man who complained only of posttraumatic low back discomfort. The ossification of the tumor appears to have been therapeutic. Mucin production may be a defense mechanism. PMID- 1908064 TI - Accurate stereotactic injection by radially curved injection needles. AB - A method has been developed for planning, constructing, and inserting radially curved injection needles for stereotactic surgery in primates. The stereotactic coordinates of the top of a guide tube and the targeted site, together with sagittal and coronal projections of the slant of the guide tube, are provided for the computer, which calculates the length, curvature, and rotational angle at which a curved injector should be inserted through the guide tube to reach the site. Development of the method included a test surgery in which curved injectors were lowered through one set of guide tubes and straight injectors through another set, targeted on the same points in the brain. Formulas used by the programs are presented, and the source code for the software is available on request. PMID- 1908065 TI - Metabolic anatomy of the focal epilepsy produced by cessation of chronic intracortical GABA infusion in the rat. AB - Cessation of chronic (5 days), unilateral infusion of GABA into the somatomotor cortex of rats induces focal epileptic spikes which remain limited to the infused site and never evolve into generalized seizures. We have considered this finding as a new model of focal epilepsy and named it "GABA withdrawal syndrome". In the present study, we have measured local cerebral glucose utilization in order to map the cortical and subcortical regions involved in the GABA withdrawal syndrome. Local cerebral glucose utilization increased two- to three-fold in a 1 1.5 mm diameter area, involving all the cortical layers at the GABA-infusion site. This hypermetabolic area contained a central (1-2 mm diameter) hypometabolic zone showing neuronal depopulation in some animals. Except for the epileptic focus, the hemisphere ipsilateral to the infusion site was slightly hypometabolic. However, there was a large increase (three- to five-fold) in some ipsilateral thalamic nuclei (posterior oralis, ventralis postero-lateralis, centralis lateralis, ventralis lateralis and reticularis thalami nucleus). The local cerebral glucose utilization of the contralateral cortex and thalamus were unchanged. The present results confirm the focal nature of the epileptogenic syndrome produced by stopping chronic, intracortical GABA infusion. These results are markedly different from those described in the penicillin focal epilepsy model. Our data also show that specific ipsilateral thalamic relays may, by an as yet unknown mechanism, play a role in maintaining paroxysmal activity during the GABA withdrawal syndrome. PMID- 1908066 TI - c-FOS-like immunoreactivity in rat brainstem neurons following noxious chemical stimulation of the nasal mucosa. AB - It has previously been shown that noxious and non-noxious peripheral stimuli induce c-fos expression in spinal dorsal horn neurons. In the present study we have examined the expression of c-fos in brainstem neurons following noxious chemical stimulation of the respiratory region of the nasal mucosa. In urethane anaesthetized rats we injected mustard oil or applied CO2 pulses to the right nasal cavity. In control animals we applied paraffin oil or a continuous flow of air. A further group of control animals was anaesthetized and not subjected to any experimental treatment. Two hours after the first stimulus the rats were perfused with 4% phosphate-buffered paraformaldehyde. Brainstem sections were incubated with primary antiserum against the FOS protein and processed according to the ABC method. Only the mustard oil-treated rats had obvious signs of rhinitis and displayed FOS-positive cells in laminae I and II of the subnucleus caudalis and in the subnucleus interpolaris of the trigeminal brainstem nuclear complex as well as in the medullary lateral reticular nucleus. These areas are known to be involved in the processing of nociceptive information. Although CO2 pulses applied to the nasal mucosa are known to evoke pain sensations in man we did not observe any FOS-positive neurons in trigeminal and reticular brainstem areas of CO2-treated rats. This lack of c-fos expression probably results from the fact that unlike mustard oil, CO2 did not induce any apparent inflammatory reactions. In all animals c-fos expression was found in the nucleus of the solitary tract and in the area postrema. Staining in these areas might partly result from factors related to anaesthesia, changed respiration parameters and stress. Since the mustard oil-treated rats displayed the highest levels of immunoreactivity in the nucleus of the solitary tract and in the area postrema, additional effects specifically related to nociceptive input are very likely. PMID- 1908067 TI - c-JUN-like immunoreactivity in the CNS of the adult rat: basal and transynaptically induced expression of an immediate-early gene. AB - An immunocytochemical study of dorsal root ganglia, spinal cord and medulla oblongata was performed with antisera against the c-jun proto-oncogene encoded protein. The c-JUN-like immunoreactivity was restricted to the cell nucleus. In the CNS of untreated rats a basal c-JUN-like immunoreactivity was present in the nuclei of two types of neurons: motor and autonomic. Labelled nuclei could be seen in many motoneurons of the ventral horn of the entire length of spinal cord and the lower medulla oblongata, as well as in the area of the nucleus hypoglossus, the dorsal motor nucleus of nucleus vagus, nucleus ambiguus, nucleus facialis, nucleus abducens and motor nucleus of nucleus trigeminus. Additionally, labelled nuclei were found in the preganglionic sympathetic and preganglionic parasympathetic cells of the nucleus intermediolateralis and nucleus intercalatus in the spinal cord. In the medulla oblongata we found a cluster of cells with c JUN-like immunoreactivity in an area between the dorsomedial part of the oral nucleus spinalis trigeminalis and the lateral border of the knee of facial nerve. Additionally, a second cluster of c-JUN-like immunoreactivity cells was visible between the ventromedial part of the oral nucleus spinalis trigeminalis and the lateral border of the rostral nucleus facialis. Examination of the characteristics of all cell groups with a basal c-JUN-like immunoreactivity in the spinal cord and lower brainstem revealed an overlapping distribution with cholinergic cell groups. Basal c-JUN-like immunoreactivity was also seen in the dorsal root ganglion cells. We examined the factors which can effect the expression of the c-JUN protein. Maximal expression of c-JUN-like immunoreactivity was observed after electrical stimulation of primary afferents. Stimulation of sciatic nerve at a strength sufficient to recruit A delta- and C fibres produced c-JUN-like immunoreactivity in many nuclei of the ipsilateral dorsal horn of the lumbar spinal cord. c-JUN-like immunoreactivity was first detectable at 30 min following the end of stimulation, reached a maximum after 1 h, remained unchanged for another 1 h and declined to the basal level after 16 h. The distribution of c-JUN-like immunoreactivity in the lumbar cord coincided with the region of termination of sciatic nociceptive afferents. Contralateral c-JUN like immunoreactivity appeared after 4 h. After noxious mechanical stimulation of the plantar hindpaw c-JUN-like immunoreactivity occurred in the spinal area of termination of nociceptive afferents of the tibial nerve. Noxious stimulation did not provoke additional c-JUN-like immunoreactivity in dorsal root ganglia.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1908068 TI - Ascites and pleural effusions associated with endometriosis. AB - We report a case of ascites and bilateral pleural effusions associated with an endometrioma in a 26-year-old woman of Chinese descent. She had a right salpingo oophorectomy and partial omentectomy performed, and she received leuprolide acetate depot injections after the operation. We believe this is the first description of use of a GnRH agonist to treat this rare condition. PMID- 1908069 TI - Treatment of adenomyosis with long-term GnRH analogues: a case report. AB - Presented here is the first reported case of biopsy-proved adenomyosis treated medically with long-term GnRH analogue. Uterine volume, as calculated by serial ultrasound measurements, was reduced by 65% after 4 months and remained small several months after discontinuation of therapy. Size reduction was accompanied by amenorrhea and relief of severe dysmenorrhea. Though not proposed as a substitute for surgery, GnRH analogue may be useful as a surgical adjuvant or for temporary reduction of symptoms. PMID- 1908070 TI - New contraceptive causes controversy. PMID- 1908072 TI - Annual meeting of the American Academy of Otolaryngology--Head and Neck Surgery Foundation, Inc. Kansas City, Missouri, September 22-26, 1991. 1991 official program and abstracts. PMID- 1908073 TI - A double lumen catheter for gastro-jejunal tube: feeding of debilitated infants. PMID- 1908071 TI - [Comparative study of acetate and bicarbonate hemodialysis in children with chronic uremia]. AB - Comparative studies on 5 children suffering from chronic uremia were performed regarding the efficacy of acetate and bicarbonate hemodialysis. Clinical symptoms, acid-base and blood gas analysis, serum osmolality, blood pressure and EEG were examined. On authors experience the patients tolerated better the bicarbonate dialysis. Laboratory data and blood pressure were found to be closer to the normal values too. The abnormality of EEG made after bicarbonate dialysis were not so expressed than that of acetate dialysis. On the basis of this examinations the authors suggest the bicarbonate hemodialysis in uremic patients with severe cardiovascular and/or neurological complications. PMID- 1908074 TI - [Radiotherapy of intracranial germinomas]. AB - Between 1978 and 1988, 28 patients with intracranial germinoma, verified or presumed, were treated with radiation. The diagnosis was made based on histology in 6 cases, on cerebrospinal fluid (CSF) cytology in 2 cases and on clinical (response to radiation) and radiological findings in the remaining 20 cases. The target volume was the primary site plus whole brain in 23 cases, whole brain in 4 cases and the primary site only in 1 case. Whole spinal irradiation was undertaken for 14 patients, including 9 patients of high risk group, i.e., with positive findings in CSF cytology, suspected subarachnoid space seeding, multifocal tumors, infiltration to the ventricular wall or previous surgery for the tumor. The average dose was 52.8 Gy to the tumor, 28.7 Gy to the whole brain and 21 Gy to the spinal axis. Five and ten-years survival rate were 100% and 96%, respectively. No intracranial recurrence or spinal metastasis has been found so far. Therefore no spinal irradiation seems to be unnecessary for non-high risk group of patients. Approximately 20 Gy should be sufficient, if spinal irradiation is to be indicated for high risk group. The dose for the primary tumor and whole brain could have been diminished to 40 Gy and 20 Gy, respectively. PMID- 1908075 TI - Multi-subunit proteins on the surface of filamentous phage: methodologies for displaying antibody (Fab) heavy and light chains. AB - The display of proteins on the surface of phage offers a powerful means of selecting for rare genes encoding proteins with binding activities. Recently we found that antibody heavy and light chain variable (V) domains fused as a single polypeptide chain to a minor coat protein of filamentous phage fd, could be enriched by successive rounds of phage growth and panning with antigen. This allows the selection of antigen-binding domains directly from diverse libraries of V-genes. Now we show that heterodimeric Fab fragments can be assembled on the surface of the phage by linking one chain to the phage coat protein, and secreting the other into the bacterial periplasm. Furthermore by introducing an amber mutation between the antibody chain and the coat protein, we can either display the antibody on phage using supE strains of bacteria, or produce soluble Fab fragment using non-suppressor strains. The use of Fab fragments may offer advantages over single chain Fv fragments for construction of combinatorial libraries. PMID- 1908077 TI - PREPP-ared for take-off (post-registration education practice project). PMID- 1908076 TI - cDNA cloning of the murine 30-kDa protein homologous to the 32-kDa subunit of human replication protein A. PMID- 1908078 TI - Demonstration of P29, an oestrogen receptor-associated tumor marker, in human term placenta. AB - A Mr29,000 serine phosphoprotein (P29) related to oestradiol receptor was studied in human term placenta with the use of a specific monoclonal antibody (D5). D5 was used with two different methods, immunohistochemistry and immunoradiometry. For immunohistochemistry, an indirect immunoperoxidase method was chosen to detect P29 in methacarn-fixed, wax-embedded sections. P29 was mostly confined to the syncytiotrophoblast surrounding placental villi, staining being positive in both cytoplasm and nuclei. The stroma of villi was negative. Content of P29 was uniformly high in crude placental cytosol, as measured by immunoradiometry assays. Specificity of D5 against P29 in placenta was tested by an immunoblotting technique. This showed a single band corresponding to a molecular weight of 29 kDa. The biological meaning of the finding is unknown at present. PMID- 1908079 TI - Potential for increasing high-density lipoprotein cholesterol, subfractions HDL2 C and HDL3-C, and apoprotein AI among middle-age women. AB - BACKGROUND: Studies have shown high-density lipoprotein cholesterol (HDL-C) to be a strong predictor of cardiovascular disease (CVD) risk. METHODS: Determinants of HDL-C and apoprotein AI concentrations were evaluated cross-sectionally in 1987 among 429 women, ages 45-54, from a population-based study of CVD risk factors through menopause (the Healthy Women Study, University of Pittsburgh). RESULTS: Subjects were healthy and not taking hormone replacement therapy. Results showed levels of HDL-C (mg/dl) to range from 23 to 117, HDL2-C from 0 to 53, HDL3-C from 16 to 66, and apoprotein AI from 87 to 204. Multivariate analyses which included age, cigarettes/day, alcohol intake (g/day), physical activity (Paffenbarger questionnaire), body mass index (BMI), and waist/hip ratio (WHR) showed that women who smoked greater than or equal to 20 cigarettes a day, reported little or no alcohol intake, expended less than 500 kcal/week, and were in the highest quintile of BMI and WHR had, on average, 33 mg/dl lower HDL-C than slender, nonsmoking women who drank moderately and exercised. HDL2-C showed a similar pattern, whereas the HDL3-C concentration had only a modest association with these factors. HDL-C was somewhat lower among women who had stopped menstruating than among premenopausal women. The apoprotein AI level was associated with alcohol intake (positively) and BMI (negatively). CONCLUSION: Theoretically, by raising their HDL-C by 10 mg/dl, women could reduce their CVD risk by as much as one-third (based on results from the Framingham Heart Study). As CVD is the leading cause of death among postmenopausal women, the potential impact of such a reduction in risk would be large. PMID- 1908081 TI - [Clinical forms of tuberculosis of the internal genital organs in women and the principles of their ambulatory observation]. PMID- 1908080 TI - Effect of cost on the self-administration and efficacy of nicotine gum: a preliminary study. AB - METHODS. One hundred six smokers seen in a family practice received brief physician advice and a prescription for nicotine gum. Smokers were randomly assigned to pay $20, $6, or $0/box of nicotine gum and followed for 6 months. RESULTS. Decreased cost increased the incidence of obtaining gum, the amount of gum used, and the incidence of long-term use (P less than 0.05). Decreased cost also increased cessation attempts and 1-week cessation (P less than 0.05) and appeared to increase abstinence at 6-month follow-up (19% vs 6% vs 8%, P less than 0.10). Cost-benefit estimates suggest that an insurance plan, HMO, etc., would recoup any costs in subsidizing nicotine gum and perhaps incur a net financial gain. PMID- 1908082 TI - [Comparative study of the effect of preservatives on the viability of the Mycobacterium populations]. AB - A radioisotope method was applied to study preservative properties of the transportation medium and the cultural one-- chlorhexidine bigluconate was used at varying exposures. Advantages of the transportation medium over 0.2% chlorhexidine bigluconate were demonstrated using Academia H37Rv and Bov-8 strains for the purpose. PMID- 1908083 TI - [Identification of Mycobacterium and Mycobacterium tuberculosis]. AB - The identification results of 3530 Mycobacterium strains isolated from a clinical material from tuberculosis patients are presented. 3219 (91.17%) of the strains are classified AS M. tuberculosis and 331 (8.83%) as nontuberculous, containing, generally, M. fortuitum group. (96 or 2.71% of the cases). Most of the nontuberculous mycobacteria had no clinical value. Mycobacteriosis caused by these mycobacteria was diagnosed in 6 patients. Biochemical identification tests allowed one to specify the species of 19 Mycobacteria. Out of 738 environmental inoculations, mycobacteria were isolated in 43 (5.82%) cases, including 42 (97.68%) nontuberculous strains. PMID- 1908084 TI - Mutants of Agrobacterium tumefaciens with elevated vir gene expression. AB - Expression of Agrobacterium tumefaciens virulence (vir) genes requires virA, virG, and a plant-derived inducing compound such as acetosyringone. To identify the critical functional domains of virA and virG, a mutational approach was used. Agrobacterium A136 harboring plasmid pGP159, which contains virA, virG, and a reporter virB:lacZ gene fusion, was mutagenized with UV light or nitrosoguanidine. Survivors that formed blue colonies on a plate containing 5 bromo-4-chloro-3-indolyl beta-D-galactoside were isolated and analyzed. Quantification of beta-galactosidase activity in liquid assays identified nine mutant strains. By plasmid reconstruction and other procedures, all mutations mapped to the virA locus. These mutations caused an 11- to 560-fold increase in the vegetative level of virB:lacZ reporter gene expression. DNA sequence analysis showed that the mutations are located in four regions of VirA: transmembrane domain one, the active site, a glycine-rich region with homology to ATP-binding sites, and a region at the C terminus that has homology to the N terminus of VirG. PMID- 1908085 TI - Production of interferon gamma, interleukin 2, interleukin 4, and interleukin 10 by CD4+ lymphocytes in vivo during healing and progressive murine leishmaniasis. AB - The expression of interleukin (IL) 2, IL-4, IL-10, and interferon gamma (IFN gamma) by lymphocyte subsets was examined during infection of resistant C57BL/6 and susceptible BALB/c mice with the protozoan parasite Leishmania major. CD4+ and CD8+ T lymphocytes and B lymphocytes were isolated from the lymph nodes draining infectious lesions, and their RNA was examined for lymphokine transcripts. Distinct patterns of CD4+ cell cytokine expression were apparent: C57BL/6 CD4+ cells contained IFN-gamma and IL-2 mRNA, whereas BALB/c CD4+ cells expressed IL-4 and IL-10 message. CD8+ cells contributed little lymphokine expression during disease, but B cells were a major source of IL-2 mRNA in both strains of mice. BALB/c mice made resistant by treatment with anti-CD4 antibody at the time of infection repopulated lymph nodes with CD4+ cells that expressed IL-2 and IFN-gamma. Protective treatment with anti-IL-4 antibody in vivo also resulted in the appearance of CD4+ cells with increased IFN-gamma and diminished IL-4 and IL-10 expression. These data establish CD4+ cells as the primary source of IFN-gamma in healing mice and of IL-4 and IL-10 during progressive infection and confirm that the spectral extremes of this disease are characterized by the presence of CD4+ cells expressing Th1 or Th2 phenotypes in vivo. PMID- 1908087 TI - Embryonic stem cells lacking a functional inhibitory G-protein subunit (alpha i2) produced by gene targeting of both alleles. AB - The alpha i2 subunit of the inhibitory heterotrimeric guanine nucleotide-binding proteins is highly conserved in mammals and is expressed in all cell types, but its exact function is not yet defined. We have investigated the role of this protein by producing embryonic stem (ES) cells lacking a functional alpha i2 gene. These alpha i2-null cell lines regulate adenylyl cyclase and grow and differentiate in vitro the same as wild-type ES cells. Homologous recombination was used to sequentially inactivate both copies of the alpha i2 gene. The first allele was inactivated by insertion of a neomycin-resistance gene. We modified the hygromycin B-resistance gene for improved expression in ES cells and used this gene to inactivate the remaining normal allele. The techniques used should be generally applicable to other genes whether or not they are expressed in ES cells. PMID- 1908086 TI - Gamma-interferon promotes proliferation of adult human astrocytes in vitro and reactive gliosis in the adult mouse brain in vivo. AB - Reactive gliosis is a characteristic response of astrocytes to inflammation and trauma of the central nervous system. To investigate whether soluble factors (cytokines) from inflammatory mononuclear cells that accumulate at lesion sites can provide the cellular signals to initiate gliosis and to identify such cytokines, we have tested and found that supernatants derived from subsets of activated human T lymphocytes (CD8+ or CD4+) are potent mitogens for cultured human adult astrocytes. This effect is blocked by a neutralizing antibody to gamma-interferon (IFN). Recombinant IFN alone can induce proliferation of human adult astrocytes in vitro and increase the extent of trauma-initiated gliosis in the adult mouse brain. The astrocyte proliferation-inducing activity of supernatants of glial cultures treated with IFN can be completely blocked with IFN-neutralizing antibody, suggesting that the proliferative effect does not require intermediary cytokines or cells. These results implicate IFN as an important mediator of the gliosis observed in pathologic conditions of the adult central nervous system associated with infiltrating lymphocytes. PMID- 1908089 TI - Glucagon induces disaggregation of polymer-like structures of the alpha subunit of the stimulatory G protein in liver membranes. AB - The hydrodynamic behavior of G alpha s, the alpha subunit of the stimulatory guanine nucleotide-binding regulatory protein (G protein), in octyl glucoside extracts of rat liver membranes was investigated. As was previously shown for G proteins similarly extracted from brain synaptoneurosomes, G alpha s behaved as polydisperse structures with S values higher than that of heterotrimeric G proteins. At concentrations of guanosine 5'-[gamma-thio]triphosphate (GTP[gamma S]) greater than 100 microM, incubation with membranes led to smaller structures having S values in the range of 4-5 S. Incubation of liver membranes with glucagon also caused a marked increase in structures having these S values; glucagon action required the presence of low concentrations of GTP[gamma S] (maximal, 10 microM), was rapid (within 10 sec), and was not observed with vasopressin, angiotensin II, or glucagon-(19-29). When G alpha s in its membrane bound form was [32P]ADP-ribosylated by cholera toxin and the treated membranes were extracted with octyl glucoside, greater than 35% of the labeled G alpha s was found in material that sedimented through sucrose gradients and contained relatively low levels of immunoreactive G alpha s. Glucagon selectively converted the apparently large molecular weight structures to the 4-5 S structures in the presence of GTP[gamma S], even at 1 mM (the maximal effect of the nucleotide alone), when incubated with the toxin-treated membranes. These findings suggest that the glucagon receptor selectively interacts with polymer-like structures of G alpha s and that activation by GTP[gamma S] results in disaggregation. The role of the beta and gamma subunits of G proteins in the hormone-induced process is not clear since the polymer-like structures extracted with octyl glucoside are devoid of beta and gamma subunits. PMID- 1908088 TI - Selection of unrelated donors for bone marrow transplantation is improved by HLA class II genotyping with oligonucleotide hybridization. AB - As the demand for donors for bone marrow transplantation increases, the use of HLA-matched, genetically unrelated donors represents a promising strategy. It is well documented that the clinical outcome of bone marrow transplantation is directly dependent on optimal matching for HLA class I and class II specificities. Molecular studies have revealed the existence of a much larger number of HLA class II alleles than was anticipated, many of which cannot be recognized by routine serological typing. Currently this "hidden" polymorphism represents a major limitation to the generalized use of unrelated donors for bone marrow transplantation. It has recently become possible, however, to identify HLA allelic polymorphism directly at the DNA level by hybridization with sequence specific oligonucleotide probes ("HLA oligotyping") after amplification of DNA by polymerase chain reaction. In this study, we have investigated whether donor recipient pairs that are fully matched for HLA by serology are truly HLA-DR, -DQ, and -DP identical and to what extent class II differences influence the primary mixed lymphocyte culture. We show that HLA oligotyping, performed on 50 pairs of HLA class I and II serologically matched individuals, can indeed reveal phenotypically relevant allelic differences at either DRB or DQB loci in 56% of these pairs and can therefore improve HLA class II typing and the choice of bone marrow donors quite significantly. Oligotyping for DRB/DQB/DPB polymorphism also allows prediction of a positive mixed lymphocyte culture, as established in 31 donor/recipient combinations, and even detection of polymorphic differences that were not revealed by this test. This approach is well suited for accurate HLA typing of large pools of bone marrow donors and was successfully applied to select fully matched donors for bone marrow transplantation. PMID- 1908090 TI - Genetic analysis of microtubule motor proteins in Drosophila: a mutation at the ncd locus is a dominant enhancer of nod. AB - The nod (no distributive disjunction) and the ncd (non-claret disjunctional) mutations are both female-specific, recessive meiotic mutations in Drosophila melanogaster. Mutations at either locus show high frequencies of nondisjunction at meiosis I and both have been shown to encode kinesin-like proteins. Unlike the ncd mutation, which affects all chromosome pairs, the nod mutation affects only the disjunction of nonexchange chromosomes. Although both the nod and ncd mutations are fully recessive, females doubly heterozygous for nod and ncd mutations show levels of X and fourth chromosome nondisjunction that are 6- to 35 fold above those observed in control females. Exchange between chromosomes can suppress this effect; thus, only nonexchange chromosomes segregating via the distributive system are sensitive in double heterozygotes. Since the phenotype of double heterozygotes mimics that of the nod mutation, we infer that ncd is a dominant enhancer of nod. Failure of ncd to fully complement nod reveals the chromosome segregation machinery to be dosage sensitive. The probability that the distributive system will fail is enhanced in females simultaneously haploinsufficient at the nod and ncd loci. PMID- 1908091 TI - Antibodies to poly[(2----8)-alpha-N-acetylneuraminic acid] and poly[(2----9) alpha-N-acetylneuraminic acid] are elicited by immunization of mice with Escherichia coli K92 conjugates: potential vaccines for groups B and C meningococci and E. coli K1. AB - Meningitis and other systemic infections caused by group B Neisseria meningitidis and Escherichia coli K1 remain important problems. The capsular polysaccharides (CPs) of these pathogens (poly[(2----8)-alpha-N-acetylneuraminic acid] or poly(alpha 2-8NeuNAc] are identical and are virulence factors and protective antigens for both. CP vaccines for these pathogens are not available because poly(alpha 2-8NeuNAc) alone, as a complex or a conjugate, is poorly immunogenic. Because oligomers of poly(alpha 2-8NeuNAc) in fetal brain and other tissues bind antibodies in vitro, it has been suggested that antibodies to this CP might be pathologic. We synthesized conjugates of this CP with tetanus toxoid under conditions that avoid lactone formation. Using this scheme, we also synthesized conjugates of group C meningococcal CP (poly[(2----9)-alpha-N-acetylneuraminic acid] or poly(alpha 2-9NeuNAc] and of E. coli K92 CP [poly(alpha 2-8, alpha 2 9NeuNAc)]. When injected s.c. in saline into mice, conjugates of poly(alpha 2 8NeuNAc) or poly(alpha 2-9NeuNAc) elicited homologous antibodies. E. coli K92 conjugates elicited both poly(alpha 2-8NeuNAc) and poly(alpha 2-9NeuNAc) antibodies. Both components of the conjugates expressed T-dependent immunologic properties under conditions and dosages acceptable for clinical evaluation. Poly(alpha 2-8NeuNAc) antibodies elicited by the homologous or the K92 conjugates had lower binding activities at 37 degrees C than at 22 degrees C. "Natural" poly(alpha 2-8NeuNAc) antibodies were present in almost all matched pairs of human maternal and cord sera; most cord levels were higher than in corresponding maternal sera. These findings suggest that increased levels of poly(alpha 2 8NeuNAc) IgG antibodies elicited by our conjugates will confer protective immunity to group B meningococci and E. coli K1 and will not be pathologic. PMID- 1908092 TI - Transforming growth factor beta stimulates urokinase-type plasminogen activator and DNA synthesis, but not prostaglandin E2 production, in human synovial fibroblasts. AB - Transforming growth factor beta (TGF-beta) is usually associated with matrix formation and tissue repair; in contrast, cellular expression of the serine proteinase, urokinase-type plasminogen activator (u-PA) is often correlated with tissue remodeling, as well as with cell migration and transformation. We report here that purified recombinant human TGF-beta (greater than or equal to 300 pg/ml) can stimulate rapidly (within 2 h) the u-PA activity of nonrheumatoid synovial fibroblast-like cells. As for interleukin 1 (IL-1), u-PA mRNA levels are raised in response to TGF-beta, but unlike IL-1, no increase in prostaglandin E2 levels occurs. In contrast to a number of other examples in the literature, in which these two cytokines have opposing actions, TGF-beta can potentiate the action of optimal concentrations of IL-1 in enhancing u-PA expression. These effects of TGF-beta are similar to those of all-trans-retinoic acid. In addition, synovial fibroblast DNA synthesis was stimulated by TGF-beta. Because TGF-beta has been detected in the synovia of patients with rheumatoid arthritis and has been shown to reduce the collagenase levels and proliferation of synovial fibroblast-like cells, it has been proposed by others to be involved beneficially in the reparative processes occurring in arthritic lesions. However, on the basis of our findings, we propose alternative functions for this cytokine--namely, roles in the destructive events as well as in the synovial hyperplasia observed in rheumatoid joints. PMID- 1908093 TI - Mutant LexA proteins with an increased rate of in vivo cleavage. AB - LexA repressor of Escherichia coli is inactivated by a specific cleavage reaction that requires activated RecA protein in vivo. This cleavage reaction can proceed in vitro in the presence of activated RecA or as an intramolecular RecA independent reaction, termed autodigestion, that is stimulated by alkaline pH. Here we describe a set of LexA mutant proteins that undergo a greatly increased rate of specific cleavage in vivo, compared with wild-type LexA. Efficient in vivo cleavage of these mutant proteins also took place without RecA. Several lines of evidence suggest that cleavage occurred via a mechanism similar to autodigestion. These mutations changed Gln-92, which lies near the cleavage site, to tyrosine, phenylalanine, or tryptophan. The latter mutation increased the rate of cleavage approximately 500-fold. These findings imply that the rate of wild type LexA cleavage has been optimized during evolution to make the SOS system properly responsive to DNA-damaging treatments. Availability of these mutants will aid in the understanding of rate-limiting steps in intramolecular reactions. PMID- 1908094 TI - Duplication of the gamma-globin gene mediated by L1 long interspersed repetitive elements in an early ancestor of simian primates. AB - Regions surrounding the single gamma-globin gene of galago and the duplicated gamma 1- and gamma 2-globin genes of gibbon, rhesus monkey, and spider monkey were sequenced and aligned with those from humans. Contrary to previous studies, spider monkey was found to have not one but two gamma-globin genes, only one of which (gamma 2) is functional. The reconstructed evolutionary history of the gamma-globin genes and their flanking sequences traces their origin to a tandem duplication of a DNA segment approximately 5.5 kilobases long that occurred before catarrhine primates (humans, apes, and Old World monkeys) diverged from platyrrhines (New World monkeys), much earlier than previously thought. This reconstructed molecular history also reveals that the duplication resulted from an unequal homologous crossover between two related L1 long interspersed repetitive elements, one upstream and one downstream of the single ancestral gamma-globin gene. Perhaps facilitated by the redundancy resulting from the duplication, the gamma-globin genes escaped the selective constraints of embryonically functioning genes and evolved into fetally functioning genes. This view is supported by the finding that a burst of nonsynonymous substitutions occurred in the gamma-globin genes while they became restructured for fetal expression in the common ancestor of platyrrhines and catarrhines. PMID- 1908095 TI - Gene sequences suggest inactivation of alpha-1,3-galactosyltransferase in catarrhines after the divergence of apes from monkeys. AB - The glycosylation enzyme alpha-1,3-galactosyltransferase (alpha 1,3GT; UDPgalactose:beta-D-galactosyl-1,4-N-acetyl-D-glucosaminide alpha-1,3 galactosyltransferase, EC 2.4.1.151) displays a unique pattern of distribution in mammals. It synthesizes an abundance of Gal(alpha 1-3)Gal(beta 1-4)GlcNAc-R (alpha-galactosyl) epitopes within the Golgi apparatus of cells of nonprimate mammals, prosimians, and New World monkeys (platyrrhines). The catarrhines, which include Old World monkeys, apes, and humans, lack this enzyme activity because of the inactivation of the alpha 1,3GT gene. In contrast, the catarrhines produce large amounts of antibodies, designated anti-Gal, against the alpha-galactosyl epitope. The inactivation of the alpha 1,3GT gene in ancestral catarrhines was probably the result of an intensive evolutionary pressure for alteration in the makeup of cell surface carbohydrates (i.e., suppression of alpha-galactosyl epitope expression) and for the production of the anti-Gal antibody. To determine the period in which the alpha 1,3GT gene was inactivated in ancestral catarrhines, comparative sequencing of a 370-base-pair region of this gene was performed by polymerase chain reactions with DNA of various primates. The data suggest that alpha 1,3GT inactivation occurred rather late in the course of catarrhine evolution (less than 28 million years ago), as separate events in apes and in Old World monkeys, after the two groups diverged from each other. PMID- 1908097 TI - Analysis of active renin heterogeneity. AB - Active renin is a heterogeneous enzyme that can be separated into multiple forms with high-resolution isoelectric focusing. The isoelectric heterogeneity may result from differences in glycosylation between the different forms. In order to determine the relationship between active renin heterogeneity and differences in composition or attachment of oligosaccharides, two separate experiments were performed: (i) Tunicamycin, which interferes with normal glycosylation processing, increased the proportion of relatively basic renin forms secreted into the incubation media by rat renal cortical slices. (ii) Endoglycosidase F, which enzymatically removes carbohydrate from some classes of glycoprotein, similarly increased the proportion of relatively basic forms when incubated with active human recombinant renin. In addition, further studies with inhibitors of human renin activity revealed that the heterogeneous renin forms were similarly inhibited by two separate renin inhibitors. These results are consistent with the hypothesis that renin isoelectric heterogeneity is due in part to differences in carbohydrate moiety attachment and that the heterogeneity of renin does not influence access of direct renin inhibitors to the active site of renin. PMID- 1908096 TI - Molecular characterization of severe hemophilia A suggests that about half the mutations are not within the coding regions and splice junctions of the factor VIII gene. AB - Hemophilia A is an X chromosome-linked disorder resulting from deficiency of factor VIII, an important protein in blood coagulation. A large number of disease producing mutations have been reported in the factor VIII gene. However, a comprehensive analysis of the mutations has been difficult because of the large gene size, its many scattered exons, and the high frequency of de novo mutations. Recently, we have shown that nearly all mutations resulting in mild-to-moderate hemophilia A can be detected by PCR and denaturing gradient gel electrophoresis (DGGE). In this study, we attempted to discover the mutations causing severe hemophilia A by analyzing 47 unselected patients, 30 of whom had severe hemophilia and 17 of whom had mild-to-moderate disease. Using DGGE as a screening method, we analyzed 99% of the coding region, 94% of the splice junctions, the promoter region, and the polyadenylylation site of the gene. We found the mutation in 16 of 17 (94%) patients with mild-to-moderate disease but in only 16 of 30 (53%) patients with severe hemophilia A. Since DGGE after computer analysis appears to detect all mutations in a given fragment, the lower-than-expected yield of mutations in patients with severe disease is likely not due to failure of the detection method; it is probably due to the presence of mutations in DNA sequences outside the regions studied. Such sequences may include locus controlling regions, other sequences within introns or outside the gene that are important for its expression, or another gene involved in factor VIII expression that is very closely linked to the factor VIII gene. PMID- 1908098 TI - Temporal effect of prolactin on the activities of lactose synthetase, alpha lactalbumin, and galactosyl transferase in mouse mammary gland explants. AB - The onset of the prolactin (PRL) stimulation of lactose synthesis is between 4 and 8 hr after adding PRL to cultured mouse mammary tissues. The synthesis of lactose is catalyzed by the enzyme lactose synthetase, which is composed of two parts, alpha-lactalbumin and galactosyl transferase. In time-sequence studies, it was found that the activity of galactosyl transferase is enhanced by PRL in concert with the onset of the PRL stimulation of lactose synthesis. In contrast, the earliest detectable effect of PRL on alpha-lactalbumin activity occurred 24 hr after adding PRL to the cultures. It is, therefore, apparent that the rate limiting component for the PRL stimulation of lactose synthesis in cultured mouse mammary tissues is galactosyl transferase activity. PMID- 1908099 TI - Bioactivity of plasma prolactin in ovariectomized, diethylstilbestrol-treated Long-Evans and Holtzman rats after thyrotropin-releasing hormone or bromocriptine administration. AB - The objective of this study was to determine the effects of thyrotropin-releasing hormone (TRH) and bromocriptine on plasma levels of biologically active prolactin in ovariectomized, diethylstilbestrol (DES)-treated rats. Female Long-Evans and Holtzman rats were ovariectomized and each was given a subcutaneous implant of diethylstilbestrol (DES). One week later, groups of DES-treated rats were fitted with indwelling intra-atrial catheters, and 2 days later blood samples were withdrawn before and at 1, 2, 5, 10, and 20 min after intravenous administration of TRH (250, 500, or 1000 ng/rat). Blood samples were obtained from other groups at 4 weeks of DES treatment by orbital sinus puncture under ether anesthesia before and at 30, 60, and 120 min after bromocriptine administration (2.5 mg/rat sc). Plasma was assayed for prolactin by conventional radioimmunoassay (RIA) and by Nb2 lymphoma bioassay (BA). Holtzman rats released significantly more prolactin following TRH than did Long-Evans rats when the RIA was used to measure prolactin. However, when the BA was used to assay prolactin in the same samples, the Long-Evans rats released more prolactin than did the Holtzman rats. In addition, the ratio of the BA to RIA values was significantly increased in both strains following TRH, but the greatest increase was observed in the Long-Evans rats, in which the ratio was 4.5 at the peak of the TRH-induced rise in plasma prolactin. Gel filtration chromatography of plasma obtained at 5 min after TRH treatment in Long-Evans rats revealed large molecular forms of prolactin with BA to RIA ratios of 4-5. In addition, monomeric prolactin had a BA to RIA ratio of 2. Bromocriptine treatment reduced prolactin levels in both strains, but the effect was more rapid in Holtzman than in Long-Evans rats. In addition, bromocriptine treatment of Holtzman, but not Long-Evans, rats significantly reduced the BA to RIA ratio of plasma prolactin. The results indicate that TRH and bromocriptine affect the release of biologically active prolactin to a greater extent than prolactin detected by antibody in the RIA, and that Long Evans and Holtzman rats respond to these secretagogues differently with regard to BA to RIA comparisons. PMID- 1908100 TI - Triacylglycerol lipase mediated release of arachidonic acid for prostaglandin synthesis in rabbit kidney medulla microsomes. AB - The effect of triarachidonin on the synthesis of prostaglandins in rabbit kidney medulla microsomes was examined. Medulla microsomes were incubated with triarachidonin in 0.1 M--Tris/HCl buffer (pH 7.0) containing reduced glutathione and hydroquinone and the formed prostaglandin E2, prostaglandin F2 alpha and prostaglandin D2 were measured by high-pressure liquid chromatography using 9 anthryldiazomethane for derivatization. The addition of triarachidonin (1-10 microM) stimulated prostaglandin formation in a dose-dependent manner. Under our incubation conditions rabbit kidney medulla was found to produce prostaglandin E2 mainly. When arachidonic acid, instead of triarachidonin, was added to the incubation mixture of microsomes, the identical profile of prostaglandin products was obtained. When the pH of the reaction mixture was changed from 7.0 to 8.0, the rate of triarachidonin-induced prostaglandin E2 formation was approximately 60% of that observed at pH 7.0. Studies utilizing Ca2+ and EGTA revealed that triacylglycerol lipase of kidney medulla is independent of Ca2+. The addition of epinephrine made the stimulatory effect of triarachidonin on prostaglandin E2 formation more pronounced. These results suggest that epinephrine-activated triacylglycerol lipase is present in the renomedullary microsomes, and this enzyme activity is a potential mediator of release of arachidonic acid for prostaglandin synthesis in the kidney medulla. PMID- 1908102 TI - Changes in thromboxane A2 generation and plasma lipid pattern in pseudomenopause induced by gonadotropin releasing hormone (GnRH) analogue buserelin. AB - An increased risk of cardiovascular disease has been found in postmenopausal women in comparison to premenopausal women. The aim of this study was to investigate platelet function, blood clotting and plasma lipid levels in 12 women with a condition of hypoestrogenism, similar to the postmenopausal status induced by treatment with the GnRH analogue buserelin for uterine leiomyoma. Platelet aggregation in whole blood and platelet-rich plasma (PRP), serum thromboxane (TX) B2 production, fibrinopeptide A (FPA) plasma levels and plasma lipid pattern were measured before and after 13 weeks of buserelin treatment. No changes of platelet aggregability were found either in whole blood or PRP. Serum TXB2 generation increased significantly after 13 weeks of therapy (p less than 0.001). No signs of increased thrombin generation were found, as indicated by unchanged FPA plasma levels. Total cholesterol plasma levels were found increased after 13 weeks, LDL cholesterol levels showed a tendency to increase although not significantly. HDL cholesterol and triglyceride concentrations were unaffected. The changes of arachidonic acid metabolism and lipid pattern suggest that buserelin treatment may induce a condition of increased thrombotic risk even if the lack of enhanced thrombin generation and increased platelet aggregability indicates that no blood clotting activation occurs. PMID- 1908101 TI - Effects of protein synthesis inhibition on PGE2 production in rabbit colonic explants cultured in vitro. AB - Colonic mucosal biopsies cultured for 6 h in the presence of cycloheximide (CH) showed a dose-dependent inhibition of protein synthesis but a biphasic PGE2 production pattern with an increase in both basal and A23187 stimulated PGE2 release at 0.2 microM. At 10 microM CH both protein synthesis as well as basal and PMA induced PGE2 production was inhibited by 90% whereas A23187 stimulated release showed a 50% decrease. At a dose of 100 microM, CH totally blocked also A23187 stimulated PGE2 release without much further decrease in protein synthesis. The effects of 10 microM CH were time-dependently reversible. In biopsies loaded with 3H-arachidonic acid (AA), 10 microM CH had no apparent effect on phospholipase A2 activity, nor could exogenous AA overcome the CH inhibition of basal PGE2 release. No inhibition of prostaglandin synthetase (PS) activity was found in homogenates of biopsies treated with 10 microM CH for 6 h. No direct effect of CH (up to 1 mM) was seen in control homogenates. It is concluded that at least one step in the PGE2 production is protein synthesis dependent. The effect is however not due to a limitation in the enzymes of the major PS system but more likely to one of its co-factors. This factor only plays a role in the intact cell and its importance seems to be reduced during A23187 conditions possibly due to altered cell status and/or other sources of PS. Commonly used high doses (100 microM) of CH give unspecific effects unrelated to inhibition of protein synthesis. PMID- 1908103 TI - Modelling approach for separating blood time-activity curves in positron emission tomographic studies. AB - A modelling approach is developed to generate the full time course of an injected radiotracer and its labelled metabolites in plasma/blood, based on measurements of the total radioactivities in withdrawn plasma/blood samples. A compartmental model is used to describe the conversion of an injected tracer to its metabolites in the body. The model equation is formulated with the total radioactivity concentration curve as the input function. The utility and characteristics of the approach in quantitative positron emission tomographic (PET) studies are shown with two examples. In the first example, using the tracer 6-[18F]fluoro-L-dopa (FDOPA), the approach is shown to derive the full time course of plasma FDOPA and its metabolites. In the second example of dynamic 15O oxygen PET, the approach is used to solve a deconvolution problem to give separated time-activity curves of 15O oxygen and 15O water in blood. The modelling approach improves the separation of blood/plasma time-activity curves and leads to better quantitative interpretation of PET results. PMID- 1908104 TI - Absorbed dose to technicians due to induced activity in linear accelerators for radiation therapy. AB - Absorbed dose to the trunk and to the hands of technicians working with accelerators for radiotherapy have been measured with TL dosimeters for seven different accelerators. The contribution from induced activity in the accelerator and from radiation transmitted through the walls of the treatment room have been estimated separately. The total annual absorbed dose to the trunk and to the hands have been estimated to be 2 mGy, of which the induced activity contributes one-third (0.7 mGy). The exposure of the technicians was found to be dominated by radiation penetrating the walls of the treatment room. For one accelerator the absorbed dose rate in the treatment room was measured continuously between 0.5 min and 48 h after end of treatment. Immediately after irradiation with high energy photons the radiation is dominated by 28Al and 62Cu T1/2 = 2.3 and 9.7 min respectively) and later by radionuclides with longer half-lives, 187W and 57Ni (T1/2 = 24 and 36 h respectively). Due to these radionuclides the radioactivity in the accelerator will build up and the technicians will therefore be irradiated every time they enter the treatment room and not only directly after a treatment with high-energy photons. PMID- 1908105 TI - Comparison of the panicogenic effect of cholecystokinin 30-33 and carbon dioxide in panic disorder. AB - 1. Twenty-two patients who met DSM-III-R criteria for panic disorder received either cholecystokinin 30-33 (25 micrograms i.v.) or 33% carbon dioxide. 2. The principal outcome measures of the study included the number and sum intensity of panic symptoms and the incidence of panic attacks. 3. The incidence of panic attacks tended (P = .07) to be higher with cholecystokinin 30-33 than with carbon dioxide. Nevertheless, patients who panicked within each group did not differ significantly with regard to the number and sum intensity of symptoms or symptom profile. 4. That cholecystokinin 30-33 and 35% carbon dioxide induced panic attacks which were qualitatively and quantitatively similar suggest that these agents might act on distinct systems that have a final common target or a final common mechanism of action. PMID- 1908107 TI - [Prostaglandin production by growth factors and its biological activity]. PMID- 1908106 TI - Deamination of 2-propyl-1-aminopentane and 2-[(2-propyl)pentylamino] acetamide by amine oxidases: formation of valproic acid. AB - 1. 2-Propyl-1-aminopentane and 2-[(2-propyl)pentylamino]acetamide are deaminated by rat liver monoamine oxidase (MAO) and aorta semicarbazide-sensitive amine oxidase (SSAO). 2. The deaminated product, 2-propylpentaldehyde, is further converted to valproic acid in vitro as well as in vivo. 3. The anticonvulsant action of these two compounds could not be substantiated, because both drugs at relatively low doses caused distinct tremor in mice and rats. 4. Both compounds also potentiate the convulsant effect induced by mercaptopropionic acid. PMID- 1908108 TI - [Interleukin-6 and its receptor]. PMID- 1908109 TI - [Atherosclerosis and growth inhibitors]. PMID- 1908110 TI - In vitro effects of arachidonic acid on the prostaglandin synthesizing system in gastric mucosa. AB - Self-destruction of the prostaglandin cyclooxygenase has been suggested to be an important factor in the regulation of endogenous prostaglandin synthesis. The present study was done in order to define the role of this substrate-induced inactivation in the regulation of prostaglandin synthesis in gastric mucosa. In tissue homogenate, the prostaglandin synthesizing capacity is rapidly inactivated at 37 degrees C, even in the absence of exogenous arachidonic acid. It was shown that this inactivation can be prevented both by EDTA as a chelator of calcium ions and by tetracaine, a specific inhibitor of the phospholipase A2. Additional exogenous arachidonic acid again inactivated prostaglandin synthesis in a dose dependent manner. In contrast, the prostaglandin synthesizing capacity in organ cultured mucosal biopsies is well preserved, although the release of endogenous substrate was activated by extracellular calcium and Ca-ionophore A23187. Furthermore, even at high concentrations of exogenous arachidonic acid present in the culture medium, the synthesizing capacity in intact biopsies was only slightly and reversibly reduced. These large differences between intact biopsies and cell free tissue preparations point to very efficient mechanisms controlling the substrate availability for the cyclooxygenase system both from endogenous and exogenous sources in intact gastric mucosa. PMID- 1908111 TI - [Economic evaluation of interventions in public health: potentials and limitations]. AB - One of the main principles of economic evaluation refers to the scarcity of resources. So, choices must and will be made concerning the commitment of these resources to one use instead another. Economic evaluation can assume different methodological forms regarding the kind and complexity of programme to be assessed and the issue of outcome valuation, but each analytic technique compares the resources consumed by different relevant alternatives with the health improvements and other consequences arising from them. From a pragmatic point of view, four types of economic evaluation can be distinguished associated with different measurement and valuation of consequences: cost-minimization, cost effectiveness, cost-utility and cost-benefit analysis. A first step of economic appraisal is definition and description of each competing alternative. Then, there are difficulties associated with measurement and valuation of both costs and effectiveness of alternatives. The assessment of public health interventions poses some special problems in terms of time profiles of cost and consequences. Most of the costs of a health programme incurred in the present while benefits will come later in the future. Therefore, cost and consequences must be discounted to reflect the existence of time preference. The last important point concerns the assessment of health consequences. Ideally, evaluation of efficacy takes the form of a well controlled randomized trial designed for this purpose. But, in many situations, this approach is not relevant, appropriate or feasible and efficacy appraisal must be developed on the basis of available data and "realistic" assumptions. So, every evaluation will contain some degree of uncertainty or imprecision and a sensibility analysis must be performed in order to test sensitivity of the results to alternative assumptions and uncertainty. PMID- 1908112 TI - [Calcium dependence of the contractile response of the aorta in the rat, rabbit and guinea pig and in the human uterine artery]. AB - The influence of extracellular Ca2+ on the contraction produced by noradrenaline (NA) (3 x 10(-6) M), KCl (60 mM) and BaCl2 (30 mM) on human uterine arteries (AUH) and aortic strips from rats, rabbits and guinea-pigs have been studied. The vessels were cut spirally and incubated in Krebs solution containing 2.5 mM Ca2+ (KN), 0 mM Ca2+ (K-0Ca) or 0 mM Ca2+ + 3 mM EDTA (K-EDTA). Both phases (fast and slow) of the response of aortic strips to NA and of the AUH to NA, KCl and BaCl2 were significantly smaller in solutions without Ca2+. Only in rabbit aortic strips the slow phase was significantly more reduced than the fast phase. Overall, the contractions of the rat aortic strips were most resistant to the absence of extracellular Ca2+. These results confirm the variability of the responses of blood vessels from different vascular beds and species to the removal of extracellular Ca2+. PMID- 1908113 TI - Characterization of gram-positive broad host-range plasmids carrying a thermophilic replicon. AB - The cryptic plasmid pBC1 (1.6 kb) isolated from Bacillus coagulans Zu1961 was genetically marked with the genes for chloramphenicol and ampicillin resistance (CmR and ApR) from the Escherichia coli plasmid pJH101. The recombinant vector obtained (pCP49, 7.0 kb) replicated and expressed CmR in B. subtilis and CmR and ApR in E. coli. Different shuttle vectors for Gram+ bacteria were also constructed by inserting pBC1 into the Staphylococcus aureus plasmid pC194. The smallest of these, pLM6 (2.8 kb), containing essentially pBC1 and the chloramphenicol acetyl transferase gene from pC194, replicated in B. subtilis at a copy number of 60. By electroporation, these plasmids were introduced and stably maintained in B. subtilis, B. amyloliquefaciens, S. aureus, S. carnosus and Lactobacillus reuteri. PMID- 1908114 TI - [Non-invasive measurement of cardiac output by the CO2 rebreathing method and its reliability in clinical practice]. AB - A Commercially available, non-invasive system for estimation of cardiac output by the CO2-rebreathing method (Sensormedicus MMC4400) was evaluated to determine its reliability in clinical practice. Values of cardiac output were obtained at rest and during mild to moderate bicycle ergometer work in patients with ischemic heart disease or hypertension. Cardiac output measured by the CO2-rebreathing method was significantly correlated with that measured simultaneously by dye dilution or thermodilution methods. Cardiac output values determined by the CO2 rebreathing method were the same as those obtained by the two invasive methods in reproducibility. When cardiac output and Vo2 were normalized for body weight, they were significantly correlated with each other. This result was obtained both by the CO2-rebreathing method, and by the two invasive methods. These results indicate that MMC4400 will provide a value for cardiac output substantially the same as that obtained by using more laborious invasive methods. Clinical use of the CO2-rebreathing method has been limited by technical difficulties. However, the recently developed non-invasive cardiac output measurement system (MMC4400) uses a microcomputer to analyze the results, and the operator can determine the values for cardiac output easily. Furthermore, it simultaneously measures VO2, VCO2 and VE, so the operator can estimate the measured values for cardiac output with background information on ventilatory gas analysis. Determination of cardiac output through the use of the CO2-rebreathing method is suitable particularly for exercise studies, and it is expected to be a useful device, in the near future, for evaluating cardiac function of patients with primary cardiac diseases. PMID- 1908115 TI - Helicobacter pylori and chronic active inflammation of the duodenum and stomach in duodenal ulcer patients treated with ranitidine, misoprostol, or an acid neutralizing agent. AB - Biopsy specimens from the stomach and duodenum of 45 duodenal ulcer patients treated with ranitidine, misoprostol, or an antacid were examined. During 4 weeks of treatment the duodenal ulcer healed in 31 patients. The treatment regimens showed no significant effect on the amount of Helicobacter-like structures (HLS) or the presence of active inflammation, either in the stomach or in the duodenum. All patients had chronic active antral gastritis before and after treatment. HLS were found histologically in 91.7% of all antral specimens, in 94.2% of the gastric corpus specimens, in 15.9% of the duodenal bulb specimens, and in 0.9% from the lower duodenal knee. The frequency of chronic active gastritis was clearly lower in the gastric corpus than in the antrum, whereas the occurrence of HLS was about the same. This may indicate a higher resistance of the gastric corpus mucosa to H. pylori. PMID- 1908116 TI - Malnutrition in hemodialysis patients. AB - Twenty-nine hemodialysis patients were studied to evaluate different laboratory measures in assessing muscle protein stores and detecting protein malnutrition. Arm muscle circumference (AMC) was used as a reference for somatic protein stores. AMC correlated with serum complement C3, plasma histidine, isoleucine, leucine, methionine and threonine concentrations as well as with body mass index. The lowest quartile of AMC was found most reliably by measuring plasma methionine, histidine, leucine and isoleucine concentrations. Protein malnutrition was detected in five patients (17%). They had significantly lower serum prealbumin and plasma leucine concentrations than the others. In the follow up of 3 years every malnourished patient died, three from septic infection. Of the others only seven died, none from infection. The analysis of plasma essential amino acid and serum prealbumin concentrations had an important role in assessing muscle protein stores as well as the protein nutrition status in hemodialysis patients. Patients with malnutrition should be detected in view of their unfavourable prognosis. PMID- 1908117 TI - Air pollution benefit-cost assessment. PMID- 1908118 TI - Concurrent processing and complexity of temporally encoded neuronal messages in visual perception. AB - The intrinsic neuronal code that carries visual information and the perceptual mechanism for decoding that information are not known. However, multivariate statistics and information theory show that neurons in four visual areas simultaneously carry multiple, stimulus-related messages by utilizing multiplexed temporal codes. The complexity of these temporal messages increases progressively across the visual system, yet the temporal codes overlap in time. Thus, visual perception may depend on the concurrent processing of multiplexed temporal messages from all visual areas. PMID- 1908119 TI - Recombinant factor VIII: an introduction. PMID- 1908120 TI - Genetic characterization of recombinant BHK-21 cells expressing factor VIII. PMID- 1908121 TI - Production and characterization of recombinant factor VIII. PMID- 1908122 TI - Preclinical and in vitro studies of recombinant factor VIII. PMID- 1908123 TI - Design of clinical studies with recombinant factor VIII. The rFactor VIII Clinical Trial Group. PMID- 1908124 TI - The pharmacokinetics of recombinant factor VIII. The rFactor VIII Clinical Trial Group. PMID- 1908125 TI - Clinical safety of recombinant factor VIII. The rFactor VIII Clinical Trial Group. AB - The safety of rFVIII has been studied in patients with severe or moderate hemophilia A in a noncontrolled observation study. A total of 40 patients participated in the study. Thirteen patients were included in stage I and 40 patients in stage II. Patients were treated at 11 centers in North America and Europe. As the results show, rFVIII is a substance with only a few unspecific side effects. Because of the constantly investigated infusion, vital signs and laboratory tests like hematology tests, serum chemistries, and urinalyses an elevation of the transaminases was found in 3 patients, which would not be correlated to rFVIII, as these patients had had in the past hepatitis B and probably non-A non-B hepatitis. Further studies with more patients will show whether these results can be confirmed. PMID- 1908127 TI - Immunologic safety of recombinant factor VIII. The rFactor VIII Clinical Trial Group. PMID- 1908128 TI - Comments on the development of inhibitor antibodies in patients using recombinant factor VIII concentrates. PMID- 1908126 TI - Comments on adverse reactions with recombinant factor VIII. PMID- 1908129 TI - Clinical efficacy of recombinant factor VIII. The rFactor VIII Clinical Trial Group. AB - This investigation has been an ongoing, multistage evaluation of the pharmacokinetics, safety and efficacy of a factor VIII concentrate prepared through recombinant DNA technology. In vivo activity of the rFVIII has been comparable to that of pdFVIII including half life and in vivo recovery. Recombinant factor VIII is safe and effective for prophylaxis and treatment of hemophilic bleeding episodes. Efficacy of rFVIII appears comparable with that of pdFVIII concentrates. Infusions were well tolerated with infrequent adverse reactions. As with any new product, the verdict regarding induction of inhibitors to factor VIII awaits evaluation of sufficient numbers of patients and passage of adequate observation time. PMID- 1908130 TI - A summary of the world-wide clinical investigations of recombinant factor VIII. PMID- 1908131 TI - The current status of recombinant human factor VIII. PMID- 1908132 TI - The need for recombinant factor VIII: historical background and rationale. PMID- 1908133 TI - Primary health services in Ecuador: comparative costs, quality, and equity of care in Ministry of Health and rural social security facilities. AB - This study of costs, quality and financial equity of primary health services in Ecuador, based on 1985 data, examines three assumptions, common in international health, concerning Ministry of Health (MOH) and Social Security (SS) programs. The assumptions are that MOH services are less costly than SS services, that they are of lower quality than SS services, and that MOH programs are more equitable in terms of the distribution of funds available for PHC among different population groups. Full costs of a range of primary health services were estimated by standard accounting techniques for 15 typical health care establishments, 8 operated by the MOH and 7 by the rural SS program (RSSP), serving rural and peri-urban populations in the two major geographical regions of Ecuador. Consistent with the conventional premise, MOH average costs were much lower than RSSP costs for several important types of services, especially those provided by physicians. Little difference was found for dental care. The lower MOH physician service costs appeared to be attributable primarily to lower personnel compensation (only partially offset by lesser productivity) and to greater economies of scope. Several measures of the quality of care were applied, with varying results. Based on staff differences and patterns of expenditures on resource inputs, notably drugs, RSSP quality appeared higher, as assumed. However, contrary to expectation, a questionnaire assessment of staff knowledge and procedures favored the MOH for quality. Program equity was judged in terms of per capita budgeted expenditures (additional measures, such as the likelihood of receiving necessary care, would have required household survey data beyond the scope of this program-based study). The results support the assumption of greater MOH financial equity, as its program reveals less variation in budgeted expenditures between different population groups covered. Additional evidence of equity, using other indicators, would be helpful in future research. The paper's findings have policy implications not only for Ecuador's health sector but also for policy-makers in other countries at similar levels of socioeconomic development. These implications are spelled out in order to guide officials wrestling with issues of efficiency, quality, and equity as they search for the best use of scarce resources to promote health. PMID- 1908134 TI - Relative costs and cost-effectiveness of extracorporeal shock-wave lithotripsy versus percutaneous nephrolithotomy in the treatment of renal and ureteric stones. AB - This paper presents empirical data from the United Kingdom National Health Service on the comparative mean hospital costs per patient of first generation extracorporeal shock wave lithotripsy (ESWL) and percutaneous nephrolithotomy (PCN) in the treatment of kidney stones. These results were subjected to a sensitivity analysis and related to evidence on the health effects of the two approaches to treatment. The hospital costs of PCN were found to be lower than for ESWL in the empirical comparison and in most but not all the scenarios developed in the sensitivity analysis. The direction of the comparison was reversed when a high throughput was assumed for ESWL and a significantly higher per diem cost for PCN than ESWL. The relative cost-effectiveness of the two modes of treatment depended on whether successful treatment was defined in terms of rendering the patient free of stones (the traditional endpoint of treatment) or the rate at which patients returned to their normal activities. PMID- 1908135 TI - [Malnutrition in old age: the importance of multi-dimensional evaluation]. AB - Protein-energy malnutrition is a frequent, but often overlooked problem in geriatric patients. To prevent malnutrition and its severe complications, a systematic strategy for identifying signs, symptoms and risk factors of malnutrition is required. In this review we present a plan for a multidimensional nutritional workup, including functional nutritional assessment. Special aspects of malnutrition management in geriatric patients are discussed (e.g. dementia, tube-feeding, environmental aspects). Use of available diagnostic and therapeutic measures for preventing malnutrition may lead to improved quality of life in many geriatric patients. PMID- 1908136 TI - [Malnutrition in old age--results of the Bethany nutrition study]. AB - One of the nutritional problems in elderly people is undernutrition, which is multifactorial in origin: The causes cannot only be seen in poor nutrition. Physical handicaps such as problems with chewing and swallowing, difficulties to cut food, immobility and mental restrictions are responsible for reduced food intake and malnutrition. Psychic and socio-economic problems such as depression, life events and loneliness may reduce appetite; poverty also contributes to the risk of undernutrition. As a result of our investigations of 300 geriatric patients, physical handicaps with influence on nutrient intake such as immobility or chewing problems were found in nearly 50% of all cases; undernutrition was observed in 22% of the patient group. In a group of 50 apparently healthy women aged 75 or older, the frequency of risk factors as well as the frequency of malnutrition was remarkably lower. These results confirm the thesis that, in most of the cases, undernutrition is related to medical problems and to the simultaneous presence of several of the above-mentioned risk factors. As a conclusion, treatment and prevention of malnutrition have to consider individually the elderly person's complete life situation. Present risk factors have to be removed, if possible; even better would be to avoid them. PMID- 1908137 TI - Effects of hypercapnia and hypocapnia on respiratory resistance in normal and asthmatic subjects. AB - The effects of hypercapnia and hypocapnia on respiratory resistance were studied in 15 healthy subjects and 30 asthmatic subjects. Respiratory resistance (impedance) was measured with the pseudo-random noise forced oscillation technique while the subjects rebreathed from a wet spirometer in a closed respiratory circuit in which end tidal carbon dioxide tension (PCO2) could be controlled. Hypercapnia was induced by partially short circuiting the carbon dioxide absorber, and hypocapnia by voluntary hyperventilation. The circulating air was saturated with water vapour and kept at body temperature and ambient pressure. A rise of end tidal PCO2 of 1 kPa caused a significant fall in respiratory resistance in both normal and asthmatic subjects (15% and 9% respectively). A fall of PCO2 of 1 kPa did not cause any significant change in impedance in the control group. In the asthmatic patients resistance increased by 13%, reactance fell by 45%, and the frequency dependence of resistance rose 240%. These findings confirm that hypocapnia may contribute to airway obstruction in asthmatic patients, even when water and heat loss are prevented. PMID- 1908138 TI - Effect of negative pressure ventilation on arterial blood gas pressures and inspiratory muscle strength during an exacerbation of chronic obstructive lung disease. AB - The effects of intermittent negative pressure ventilation have been studied in 20 patients with chronic obstructive pulmonary disease during an exacerbation of their disease. Measurements of arterial blood gas tensions and maximal inspiratory pressure (MIP) were performed before and after six hours of negative pressure ventilation or standard treatment (control day) given in random order on two consecutive days. After negative pressure ventilation the mean (SD) value of MIP increased from 68.1 (21.5) to 74.8 (20) cm H2O;* arterial oxygen tension (PaCO2) fell from 60.6 (12.2) to 50.9 (8.9) mm Hg* but PaO2 changed little (from 48.4 (7.4) to 47.6 (8.2) mm Hg). There were no significant changes on the control day in arterial blood gas tensions (PaO2 47.8 (8.1) and 48.9 (9.4) and Paco2 59.8 (10.9) and 57.5 (8.06) mm Hg) or in MIP (69.4 (22.4) and 70.9 (22.9) cm H2O). Six patients tolerated negative pressure ventilation poorly and these patients showed less improvement after negative pressure ventilation. Our results suggest that intermittent negative pressure ventilation can increase alveolar ventilation in patients with an exacerbation of chronic obstructive lung disease, particularly in those who tolerate the procedure well. Most subjects showed a fall in PaCO2 and an increase in MIP. The fact that PaO2 was unchanged despite the fall in PaCO2 suggests that gas exchange may deteriorate with negative pressure ventilation in these patients. PMID- 1908139 TI - Detection of platelet desensitization in pregnancy-induced hypertension is dependent on the agonist used. AB - The aggregation of platelets from women with pregnancy-induced hypertension (P.I.H.), or with normal pregnancies, in response to arachidonic acid, ADP, collagen or platelet activating factor (PAF) was examined. No differences in platelet aggregation between the normotensive and hypertensive women were detected when arachidonic acid or collagen were used to stimulate in vitro platelet aggregation. Higher concentrations of ADP and PAF were required to aggregate platelets from women with P.I.H. compared with platelets from normotensive controls. Platelets from women with normotensive pregnancies (n = 80) aggregated maximally in response to 20 nM PAF without exception. Reversible aggregation by platelets from women with P.I.H. (n = 25) was observed at the same concentration of PAF; again, this was found in all subjects tested. These results indicate that PAF at a concentration of 20 nM can clearly demonstrate differences in aggregation of platelets from women with normotensive pregnancy and women with P.I.H. PMID- 1908140 TI - Thrombolysis with an Escherichia coli-produced recombinant plasminogen activator (BM 06.022) in the rabbit model of jugular vein thrombosis. AB - The recombinant plasminogen activator BM 06.022 consists of the kringle 2 and the protease domains of human t-PA and is unglycosylated because of the expression in Escherichia coli. The thrombolytic and pharmacokinetic properties as well as the hemostasis effects of BM 06.022 were investigated in the rabbit model of jugular vein thrombosis. The thrombi were 125I-fibrin labeled. Intravenous bolus injection of 50, 100, 200, and 400 kU/kg BM 06.022 or 400, 800, and 1600 kU/kg alteplase over 15 s to six rabbits/dose produced a dose-dependent increase of thrombolysis determined 2 h post injection. The dose-response curve of BM 06.022 was located left compared with that of alteplase. The effective dose of 50% thrombolysis (ED50) obtained by half-logarithmic regression analysis was 163 kU/kg (= 0.28 mg/kg) for BM 06.022 and 871 kU/kg (= 1.09 mg/kg) for alteplase. At equipotent doses (50% thrombolysis), the residual concentration of fibrinogen was 74.2% and 76.5%, that of plasminogen 66.7% and 69.4%, and that of alpha 2 antiplasmin 47.3% and 46% for BM 06.022 and alteplase, respectively. Pharmacokinetic analysis for plasma activity at a dose of 400 kU/kg revealed a half-life of 18.9 +/- 1.5 min for BM 06.022, whereas alteplase was distributed with a half-life of 2.1 +/- 0.1 min, accounting for 86.7 +/- 1.9% of the total AUC, followed by a beta-phase with a half-life of 13.8 +/- 0.9 min. Plasma clearance of BM 06.022 was 4.7 +/- 0.7 ml min-1 kg-1 compared with 20 +/- 1.2 ml min-1 kg-1 for alteplase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1908141 TI - Stimulation of tissue-type plasminogen activator synthesis by retinoids in cultured human endothelial cells and rat tissues in vivo. AB - Tissue-type plasminogen activator (t-PA) and its inhibitor, plasminogen activator inhibitor 1 (PAI-1), play an important role in regulating the fibrinolytic capacity of plasma. Both t-PA and PAI-1 are synthesized by the endothelium. We report that retinoic acid (vitamin A acid) and other retinoids rather specifically stimulate the production of t-PA by cultured human umbilical vein endothelial cells. Effective retinoids induced a dose-dependent (range: 0.01-50 microM) increase in the production of t-PA of maximally about six-fold, while simultaneously causing no or only a small increase (less than two-fold) of PAI-1. The effects on t-PA synthesis were apparent by 4-8 h, and reached maximal values after about 24-48 h of incubation with retinoid. The retinoid effect on t-PA production was accompanied by increased t-PA mRNA levels, without any parallel change in PAI-1 or GAPDH mRNA concentrations. The study also shows that modifications at the carboxyl group of retinoic acid are associated with a decrease in stimulatory potency. The stimulatory pathway appears to be identical for all retinoids but distinct from a pathway by which another strong inducer, sodium butyrate, induces t-PA synthesis in endothelial cells. The induction of t PA by retinoids might involve protein kinase C (PKC) as judged by an experiment using a specific PKC inhibitor. The effect of retinoids on the fibrinolytic system in vivo was assessed by feeding rats with a vitamin A deficient diet or a diet with excess of vitamin A or other retinoids.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1908142 TI - A new intra arterial rt-PA dosage regimen in peripheral arterial occlusion: bolus followed by continuous infusion. PMID- 1908143 TI - Distribution of HLA-DRB1, -DQA1 and -DQB1 alleles and DQA1-DQB1 genotypes among Norwegian patients with insulin-dependent diabetes mellitus. AB - We have studied 87 unrelated Caucasian insulin-dependent diabetes mellitus (IDDM) patients and 181 healthy controls by oligotyping for 20 DRB1, eight DQA1 and 13 DQB1 alleles, and established their DR-DQ haplotypes and DQ genotypes. An increase of DRB1 alleles encoding DR4 was found among IDDM patients, but the distribution of DR4 subtypes did not differ among DR4-positive IDDM patients and controls. The frequency of certain DRB1-DQA1-DQB1 haplotypes and DQA1-DQB1 genotypes was significantly increased among IDDM patients. Taken together, the data suggest that IDDM is primarily associated with several (at least five) different DQ alpha beta heterodimers. PMID- 1908144 TI - Prevention of 1,2-dibromo-3-chloropropane (DBCP)-induced kidney necrosis and testicular atrophy by 3-aminobenzamide. AB - The poly(ADP-ribosyl)transferase inhibitor, 3-aminobenzamide (3-ABA), reduced morphological evidence of 1,2-dibromo-3-chloropropane (DBCP)-induced DNA damage determined by alkaline elution. The DBCP plasma, kidney, and testis tissue doses determined between 1 and 8 hr after a single intraperitoneal injection were somewhat higher with than without 3-ABA pretreatment. Furthermore, the amount of DBCP metabolites covalently bound to macromolecules was reduced to about 20-30 percent of control, indicating that 3-ABA may have an effect on the formation/detoxication of reactive DBCP metabolites. Inhibitors of replicative DNA synthesis such as hydroxyurea or stimulation of DNA replication by nephrectomy did not affect the cytotoxicity, neither did inhibitors of DNA repair such as beta-cytosine arabinoside and beta-lapachone. PMID- 1908145 TI - Suppression of the in vitro humoral immune response of mouse splenocytes by 7,12 dimethylbenz[a]anthracene metabolites and inhibition of immunosuppression by alpha-naphthoflavone. AB - Exposure to 7,12-dimethylbenz[a]anthracene (DMBA) has been demonstrated by numerous investigators to result in suppression of both humoral and cell-mediated immune responses of mice and cultured splenocytes. The mechanism(s) of this DMBA induced immunosuppression, however, is not well characterized. PAHs must be converted to reactive metabolites via cytochrome P450-dependent monooxygenase systems to exert their carcinogenic and mutagenic effects. Thus, we have hypothesized that immunosuppression seen upon exposure to DMBA may also be mediated by its reactive metabolites. The objective of this study was to determine if DMBA metabolites can suppress the in vitro, T-dependent humoral immune response to sheep red blood cells. Compounds were evaluated in the in vitro plaque-forming cell (PFC) response at concentrations of 10(-9) to 10(-5) M. DMBA and benzo[a]pyrene (B[a]P) were also evaluated for their ability to suppress the in vitro PFC response. Addition of either of these PAHs to splenocyte cultures produced a concentration-dependent suppression of the PFC response, in which B[a]P was found to be 17.5-fold more potent than DMBA. These results are in contrast to those found in vivo, where DMBA has been shown to be more potent than B[a]P at suppressing humoral immunity. The 3,4-diol metabolite of DMBA produced a concentration-dependent suppression (10(-8) to 10(-5) M) of the in vitro PFC response and was found to be 65-fold more potent than the parent compound DMBA. In contrast, the 5,6-diol metabolite of DMBA had no effect on the PFC response or cell viability. Both the 3-OH-DMBA and 7-hydroxymethyl-12-methyl benz[a]anthracene (7-OHMe-12-Me-BA) metabolites were found to be immunosuppressive at concentrations of 10(-6)M. Furthermore, suppression by 7 OHMe-12-Me-BA was observed at concentrations as low as 10(-8) M. Immunosuppression by the 7-Me-12-OHMe-BA and the di-OHMe-BA metabolites was only observed at high (10(-5) M) concentrations. The cytochrome P450 inhibitor, alpha naphthoflavone (ANF), was utilized to determine if cytochrome P450-mediated metabolism is involved in DMBA-induced suppression of the in vitro PFC response. ANF (10(-5) M) reversed the DMBA-induced immunosuppression seen at 10(-5) M and attenuated the immunosuppression at 3 x 10(-5) and 10(-4) M. The results of these studies demonstrate that several metabolites of DMBA which can be generated by the cytochrome P450-dependent monooxygenase systems are immunosuppressive in the in vitro PFC response assay. Furthermore, the cytochrome P450 inhibitor, ANF, was able to reverse DMBA-induced immunosuppression.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1908147 TI - Intestinal permeability and bacterial translocation following small bowel transplantation in the rat. AB - In addition to its role in absorbing nutrients, the intestinal mucosa provides an important barrier against toxins and bacteria in the bowel lumen. The present study evaluated gut barrier function following orthotopic (in continuity) intestinal grafting in rats. Graft histology, intestinal permeability, and bacterial translocation to the grafted mesenteric lymph nodes, the host's liver, and the host's spleen were assessed on the 3rd, 5th, and 7th postoperative days. The study group received no immunosuppression after allotransplantation. The two control groups included rats with isografts and rats with cyclosporine-treated allografts. On the 7th POD, the study animals had moderate transmural inflammation due to rejection, with normal histology in the isografts and CsA treated allografts; increased intestinal permeability, measured by urinary excretion of oral 51Cr-EDTA (P less than 0.01); and increased number of bacteria in the MLN and spleen (P less than 0.05). The number of bacteria in the MLN and spleen of the study group positively correlated with the changes in intestinal permeability (P less than 0.05). Rejection of the orthotopic intestinal graft leads to increased intestinal permeability and bacterial translocation from the lumen of the graft to the host's reticuloendothelial system. Measures to improve gut barrier function and antibiotic therapy during rejection episodes may help reduce the incidence of septic complications after intestinal grafting. PMID- 1908146 TI - Toxicokinetics of inhaled 1,3-butadiene in monkeys: comparison to toxicokinetics in rats and mice. AB - 1,3-Butadiene is a potent carcinogen in mice and a weaker carcinogen in rats. People are exposed to butadiene through its industrial use--largely in rubber production (over 3 billion pounds of butadiene were produced in 1989)--and because it is common in the environment, occurring in cigarette smoke, gasoline vapor and in the effluents from fossil fuel incineration. Epidemiological studies have provided some evidence for butadiene carcinogenicity in people. Differences in the uptake and metabolism of inhaled butadiene between rodents and primates, including people, might be reflected in differences in its toxicity. In order to compare uptake and metabolism in primates to that in rodents--for which data were already available--we exposed cynomolgus monkeys (Macaca fascicularis) to 14C labeled butadiene at concentrations of 10.1, 310 or 7760 ppm for 2 hr. Exhaled air and excreta were collected during exposure and for 96 hr after exposure. The uptake of butadiene as a result of metabolism was much lower in monkeys than in rodents. For equivalent inhalation exposures, the concentrations of total butadiene metabolites in the blood were 5-50 times lower in monkey than in the mouse, the more sensitive rodent species, and 4-14 times lower than in the rat. If the toxicokinetics of butadiene in people is more like that of the monkey than that of rodents, then our data suggest that people will receive lower doses of butadiene and its metabolites than rodents following equivalent inhalation exposures to butadiene. This has important implications for assessing the risk to humans of butadiene exposure based on animal studies. PMID- 1908149 TI - Chronic intracellular protozoan infections and kidney transplantation. PMID- 1908148 TI - OKT3 F(ab')2 fragments--retention of the immunosuppressive properties of whole antibody with marked reduction in T cell activation and lymphokine release. AB - Recent studies in mouse and man indicate that the first dose response to anti-CD3 mAbs likely results from in vivo T cell activation and concomitant lymphokine release. One approach toward amelioration of these effects involves the use of nonactivating digest fragment preparations of anti-CD3 mAbs. In the present study whole and F(ab')2 fragments of OKT3 were prepared and assayed for their immune activating and -suppressing effects on human peripheral blood mononuclear cells. Immunosuppressive effects were evaluated by quantitation of TCR modulation and coating, and by inhibition of CTL activity. Whole mAb and F(ab')2 fragments both effectively coated the TCR complex. However, whole mAb was more efficient at modulating the TCR complex, suggesting that modulation is enhanced by FcR interactions. Whole and F(ab')2 fragments of OKT3 were equally efficacious in suppressing CTL activity. Immune activation was evaluated by quantitation of proliferation, activation marker expression (IL-2R and Leu-23), and lymphokine release (TNF-alpha, gamma-IFN, and GM-CSF). Rigorously purified F(ab')2 preparations demonstrated minimal T cell activation, suggesting TCR and macrophage FcR crosslinking as necessary. Whole OKT3 mAb induced expression of IL 2R and Leu-23 activation markers on the majority of CD4+ and CD8+ cells at mAb concentrations as low as 1 ng/ml, whereas F(ab')2 fragments induced detectable, but markedly reduced expression of these markers only at mAb concentrations greater than or equal to 100 ng/ml. Similarly, whole mAb induced release of TNF alpha, gamma-IFN, and GM-CSF at low mAb concentrations, whereas F(ab')2 fragments induced detectable (though markedly reduced) levels of TNF-alpha only. However, increasing degrees of contamination with whole antibody resulted in increasing mitogenic potency of the F(ab')2 preparation, which in some cases, was actually enhanced compared with that observed with whole mAb alone. In conclusion, these studies indicate that OKT3 F(ab')2 digest fragments are markedly less potent than whole mAb in inducing T cell activation, yet they retain significant immunosuppressive effects. However, meticulous purification of F(ab')2 digest fragment preparations will likely be required to avoid T cell and macrophage activation following in vivo administration. PMID- 1908150 TI - Treatment with OKT3 and cyclosporine for acute allograft rejection. AB - In summary, we believe that our experience with concomitant use of OKT3 and either reduced-dose CyA for treatment of renal allograft rejections or full-dose CyA therapy for treatment of liver allograft rejection is both safe and possibly more effective in reversing allograft rejection than use of the antibody alone. This strategy has also allowed us to use this MAb therapy without incurring the untoward consequence of the development of hightiter anti-OKT3 antibodies that could preclude its subsequent reuse. PMID- 1908151 TI - Contributions by Paul S. Russell toward the future application of xenografting. PMID- 1908152 TI - Reversal of allograft rejection using the monoclonal antibody, Campath-1G. PMID- 1908153 TI - Neopterin, amyloid A, C-reactive protein, gamma-interferon, and interleukin-2 receptor in diagnosis of posttransplantation rejection. PMID- 1908154 TI - Comparison of CyA, OKT3, and ATG immunoprophylaxis in human liver transplantation. PMID- 1908156 TI - Ciguatera fish poisoning: treatment with intravenous mannitol. AB - Intravenous mannitol was given to 16 patients with acute ciguatera fish poisoning requiring hospital admission. Thirteen patients (81%) presented with sensory and neuromuscular symptoms; paraesthesiae and pain and weakness in the lower limbs were predominant features. Mannitol had little effect upon gastrointestinal manifestations, but a marked reduction was observed in the expected duration of neurological symptoms. Although these results are empirical and uncontrolled, they suggest that mannitol infusion may be effective in altering the clinical course of acute ciguatera fish poisoning. PMID- 1908155 TI - Preoperative prophylactic OKT3 vs RATG. A randomized clinical study in heart transplant patients. PMID- 1908157 TI - Ultrastructural localization of synaptophysin to the secretory granules of normal glucagon and insulin cells in human islets of Langerhans. AB - Immunogold labeling of the pancreatic islets in humans by means of monoclonal antibodies to synaptophysin resulted in a distinct localization of gold particles to the secretory granules of glucagon-immunoreactive cells. The same type of immunoreactivity was noted with antiserum to chromogranin A. Glucagon immunoreactivity was concentrated in the dense central core of the secretory granules. Some immunoreactivity for synaptophysin was also found in the secretory granules of the insulin-producing cells, although it was weaker in this location. PMID- 1908158 TI - Biological properties of RB51; a stable rough strain of Brucella abortus. AB - A rifampin-resistant mutant of Brucella abortus, designated RB51, was derived by repeated passage of strain 2308 on Trypticase soy supplemented with 1.5% agar and varying concentrations rifampin or penicillin. The RB51 colonies absorbed crystal violet and RB51 cell suspensions autoagglutinated, indicating a rough type colonial morphology for this strain. No O-chain component was detected in lipopolysaccharide (LPS) extracted from RB51 on SDS-PAGE gels stained with silver. Western blot analysis with the monoclonal antibody BRU 38, which is specific for the perosamine homopolymer O-chain of smooth Brucella LPS, indicated that the LPS of RB51 is highly deficient in O-chain when compared with the parenteral smooth strain 2308 or rough strain 45/20. Biochemically, RB51 resembles parental strain 2308 in its ability to utilize erythritol. Intraperitoneal inoculation of RB51 into mice results in a splenic colonization which is cleared within four weeks post infection. RB51 does not revert to smooth colony morphology upon passage in vivo (mice) or in vitro. Mice infected with RB51 produce antibodies against B. abortus antigens including class 2 and 3 outer membrane proteins but not against the O-chain. Furthermore, rabbits, goats and cattle hyperimmunized with sonicates of RB51 develop antibodies to B. abortus cellular antigens but do not develop antibodies specific for the O-chain. Immunization of mice with 1 x 10(8) viable RB51 organisms confers significant protection against challenge with virulent B. abortus strain 2308. PMID- 1908159 TI - Controlling acute Escherichia coli mastitis during the periparturient period with recombinant bovine interferon gamma. AB - The efficacy of recombinant bovine interferon (rBoIFN)-gamma against experimentally induced Escherichia coli mastitis during the periparturient period was investigated. Dairy cows intramammarily treated with rBoIFN-gamma 24 h before the E. coli challenge had fewer infected quarters, lower clinical scores, and infections of shorter duration when compared to placebo-treated animals. All rBoIFN-gamma treated cows survived the experimental E. coli challenge. However, placebo treated cows had a 42% mortality rate attributed to coliform mastitis within 3 days of the challenge. Results from this study suggest that intramammary infusion of rBoIFN-gamma can prevent the rapid, unrestricted growth of E. coli within the mammary gland and inhibit the subsequent development of an unlimited inflammatory response under experimental conditions. It is likely that controlling severe local inflammatory reactions may also decrease the pathological alterations to mammary parenchymal tissue that often accompanies acute coliform mastitis during the periparturient period. The potential for prophylactic treatment of perinatal dairy cows with rBoIFN-gamma to regulate the rate, severity, and duration of naturally occurring coliform mastitis during periods of heightened susceptibility is discussed. PMID- 1908161 TI - [Effect of thrombolytic therapy in acute myocardial infarct on incidence of ventricular late potentials]. AB - The aim of thrombolytic therapy for acute myocardial infarction is reperfusion of the infarction-related vessel. Ventricular late potentials detected by signal averaging have been demonstrated to be related to slow and inhomogeneous conduction within damaged cardiac tissue. In 75 patients with first myocardial infarction the effect of thrombolysis on ventricular late potentials was studied. Reperfusion of the infarction-related vessel could be demonstrated by coronary angiography in 53 (71%) patients. In 22 patients (29%) there was no reperfusion. In the 53 patients with successful thrombolysis the incidence of late potentials was significantly lower (9%) than in the 22 patients without reperfusion (50%). The lower incidence of late potentials may demonstrate improved ventricular electrical stability. PMID- 1908163 TI - Determination of coplanar polychlorinated biphenyl congener residues in food using HPLC fractionation. AB - An analytical method is described for determining the residues of coplanar PCB congeners exhibiting toxicological relevance, in foods of animal origin and human milk. The unsophisticated procedure, convenient for routine analyses, includes extraction and saponification of lipids, isolation of the unsaponifiable matter and its cleanup on a small silica gel column, fractionation using HPLC on a special carbon column and gas-chromatographic analysis with capillary columns and electron capture detection (ECD). PMID- 1908160 TI - Distribution patterns of apolipoproteins A1, A2, and B in the wall of atherosclerotic vessels. AB - Atherosclerotic vessels were analysed histochemically for distribution, quantity, and composition of apolipoprotein (Apo) types in the vascular wall. The specimens comprised all stages of atherosclerosis, from very discrete intimal changes to complicated lesions. The vessel specimens were marked with antibodies against human Apo A1, A2, and B. Apo A1 can be demonstrated in even the earliest stage of atherosclerosis, and increases with the progression of the disease. In the initial stage, Apo A1 is found first in lumen-adjacent layers of the intima, and is evident in deeper layers of the wall as the disease progresses. Arteries of muscular type show accumulation of Apo in an earlier stage (or in greater quantity at the same stage) than arteries of elastic type. At all stages, the amount of Apo A1 always exceeds that of A2 and B. In the intima, Apo B is higher than Apo A2, the media contains hardly any Apo B, and the adventitia has less B than A2. Within the intimal layer, Apo A1 and A2 are found in an intracellular (mainly in foam cells) or in an extracellular location, according to the stage of atherosclerosis. Apo B is almost exclusively extracellular; only cases of advanced atherosclerosis show some intracellular localization (mostly in foam cells), visualized as electron dense lamellar organelles, probably of lysosomal origin. In the media, Apo A1 and A2 are accumulated in intracellular deposits, whereas the extracellular storage of Apo A1, A2 and B is observed only in cases with the most severe damage. Our investigations suggest that the accumulation of apolipoproteins in the vascular wall is affected not only by insudation from the plasma, but also by neosynthesis and/or metabolism by locally derived cells or cells immigrating in the process of atherosclerosis. The presence of Apo A1 and A2 in the vessel wall is now documented, and their role at this site apparently differs from that in the plasma. PMID- 1908162 TI - Oral immunization of mice with temperature-sensitive Pseudomonas aeruginosa enhances pulmonary clearance of the wild-type. AB - DBA/2J mice were immunized daily for 3 days per os with 10(8)-10(9) colony forming units (c.f.u.) of two different temperature-sensitive (TS) mutants of Pseudomonas aeruginosa. At varying times after the final immunization the animals were exposed to aerosols of the parental immunotype 1, and the ability of the immunized and control mice to clear their lungs of the wild-type (WT) challenge was measured 4 h later. The number of c.f.u. remaining in the lungs of mice immunized with one mutant, D/1/8, was significantly less (p less than 0.01) than the number remaining in the lungs of control mice and mice immunized with a second TS mutant, E/9/9. PMID- 1908165 TI - [The adhesive properties of meningococci from serogroups A, B and C]. AB - The adhesive properties of 261 meningococcal strains have been studied by the methods of the hemagglutination test, the test of adhesion on buccal epithelial cells and electron microscopy. The study has revealed that adhesive properties can be observed in the strains of all groups under study (A, B and C) isolated from patients and carriers, including those isolated from the nasopharynx, blood and liquor, adhesive properties occurring in newly isolated strains with greater frequency than in museum ones. The simultaneous use of all three above-mentioned methods increases the possibility of the detection of meningococcal strains with adhesive activity. PMID- 1908164 TI - Contribution to the mode of action of univalent gold. AB - Au+ binds to the collagen structure and, therefore, the authors studied the kinetics of the interaction between sodium gold thiosulphate (SGTS) and C1q complement subcomponent, the structure of is partially collagenous. The kinetics was evaluated densitometrically and compared with that of collagen and SGTS. On the basis of those results, the effect of SGTS upon collagen type-II-induced arthritis (CIA) was investigated in Wistar rats. SGTS (20 mg per kg of body weight weekly) was administered i.m. starting i) with the first immunization dose, ii) with the second immunization dose, and iii) after the onset of arthritis. Regardless of the timing of drug administration the manifestation of arthritis was decreased, but the decrease was more expressed in the first two groups. It was concluded that SGTS administration is capable of inhibiting CIA, provided that the drug is applied sufficiently early. Since formation of antibodies to type-II collagen remained unaffected, it is feasible that the mode of action of gold complexes is based mainly on blocking the activation of complement system. PMID- 1908166 TI - [The immunological status indices of monkeys inoculated with a meningococcal B vaccine]. AB - The method for the determination of bacterial antibodies to group B meningococci was worked out. The method was used for the determination of antibodies to group B meningococcal vaccine produced in the USSR. The dynamic study of antibodies to protein, polysaccharide and lipopolysaccharide antigens of group B meningococci was made by the method of the enzyme immunoassay (EIA), and the safety of the vaccine was studied by the determination of autoantibodies active against brain tissue antigens. The data thus obtained were indicative of the immunological activity of group B protein-polysaccharide vaccines, manifested by the capacity for stimulating bactericidal antibodies whose level increased 8- to 10-fold after the immunization of monkeys in 2 and 3 injections. Similarity in the dynamics of the formation of bacteriolysins and antibodies to protein antigen, as determined in EIA, was noted. The vaccine was found to stimulate no cytotoxic anticerebral antibodies in the glia migration test, which was indicative of the safety of group B meningococcal vaccine. PMID- 1908167 TI - [The ultrastructural characteristics of the interaction of Legionella pneumophila with the infusorian protozoon Tetrahymena pyriformis]. AB - In this work the morphological features of the interaction of L. pneumophila virulent strain and T. pyriformis have been studied on the submicroscopic level in the time course of the process. The study has shown the process of the destruction of the bacterial population and the penetration of individual intact Legionella cells from the phagosome into the endoplasm of T. pyriformis after 6-9 hours of interaction in the form of the budding of the phagosome and further multiplication of Legionella in the endoplasm. As revealed in this study, T. pyriformis have two types of phagosomes characterized by different variants of the destruction of Legionella. In T. pyriformis lysosomes-like granules, mitochondria and the granular endoplasmatic network take part in the process of interaction. The process of interaction has been found to end by day 7 in the death of all protozoal cells taking part in interaction. PMID- 1908168 TI - Human endometrial epithelial cells grown on collagen in serum-free medium. Estrogen responsiveness and morphology. AB - The aim of the study was to explore the possibility of using human endometrial epithelial cells in serum-free culture as a sensitive assay for hormonal effects on the human endometrium. Glands were isolated following enzymatic digestion of the endometrial tissue and plated on a collagen matrix. The epithelial cells were grown in either medium containing serum or in supplemented serum-free medium. No morphologic difference was found between cells grown in these two media for up to 5 days, using either light or scanning electron microscopy. Secretion of prostaglandin F2 alpha (PGF2 alpha) in response to estradiol was not lower in serum-free medium than in medium containing serum for the first 2 days of culture, whereas secretion declined after prolonged incubation in the serum-free medium. This response to estradiol was clearly dose-dependent, and it was further enhanced by addition of arachidonic acid, the precursor for prostaglandin synthesis, to the medium. Co-culture of endometrial stromal cells did not influence the secretion of PGF2 alpha by epithelial cells. We conclude that the secretion of PGF2 alpha from primary cultures of human endometrial epithelial cells grown on collagen in serum-free medium can be used for a limited period as an assay of estrogenic effects on the human endometrium. PMID- 1908169 TI - Equine follicle-stimulating hormone action in cultured Sertoli cells from rat, sheep and pig. AB - Using a suspension of seminiferous tubule cells, we had previously shown that equine FSH is superactive in the male rat, i.e. that it exhibits a higher biological potency than expected from its binding activity. In this work we investigated equine FSH superactivity in rat, pig and sheep, by comparing in each species the equine FSH with the homologous FSH, both for their binding activities (in a radioreceptor assay using a testicular membrane fraction) and for their in vitro biological potencies (in a plasminogen activator assay using a Sertoli cell enriched population cultured on plastic). In the rat, the binding activity of equine FSH was identical to that of rat FSH, and the biological potency of equine FSH was 47 times higher than that of rat FSH. Hence, superactivity of equine FSH was confirmed in the rat. In the pig, equine FSH was not superactive, since it exhibited binding activity and biological potency identical to those of porcine FSH. In the sheep, the binding activity of equine FSH was 6 times higher than that of ovine FSH, and its biological potency was also higher (14 times). Therefore, equine FSH cannot be considered superactive in this species. In conclusion, equine FSH superactivity is closely related to the species from which Sertoli cells are isolated. PMID- 1908170 TI - Changes in the vitreous body pH of pigs after retinal xenon photocoagulation. AB - In an unpaired study, in vivo measurements of pH in vitreous were performed on normal pig eyes and pig eyes treated with retinal xenon photocoagulation. In one group (n = 7) the mean vitreal pH was 7.29 at a mean arterial pH of 7.41. In the other group (n = 8) two to three weeks after retinal xenon photocoagulation, a significant increase in mean vitreal pH of 0.06 to 7.35 (P less than 0.01) was observed at a similar arterial pH. Induced hypercapnia resulted in a decrease in pH vitr. and induced hypocapnia in an increase, with similar changes in pH art. The respiratory pH changes were similar in the two groups. These findings allow one to assume that, as a result of retinal photocoagulation, a change in the retinal metabolism is induced, either by a change in the relationship between aerobic and anaerobic metabolism or as a result of a general reduction of the metabolic activity. PMID- 1908171 TI - Heterotopic ossification following total hip arthroplasty: a review. AB - Heterotopic ossification is the most frequent complication of total hip arthroplasty. When formed in the para-articular tissues, it may cause pain and restriction of hip motion. The present article extensively reviews the current literature on heterotopic ossification following total hip arthroplasty with regard to epidemiologic factors, clinical presentation and possible pathogenesis. Preventive measures are emphasized. Postoperative treatment with radiation and nonsteroidal antiinflammatory drugs have yielded good results in the prevention of heterotopic ossification. On the other hand, biophosphonates were ineffective. In comparison with radiation therapy, prophylaxis with nonsteroidal antiinflammatory drugs gave better results. Further research is still needed to define the most effective and safe medication regimen. PMID- 1908172 TI - Bilateral intradeltoid ossification: a cause of glenohumeral abduction contracture. AB - A case of bilateral glenohumeral abduction contracture is presented. Two features are unique: intradeltoid ossification and progressive deformity without recent trauma. A review of the literature is given. PMID- 1908173 TI - Coeliac disease, folic acid deficiency and epilepsy with cerebral calcifications. AB - Two cases of focal occipital epilepsy with cerebral calcifications poorly responsive to antiepileptic treatment are described. In both cases coeliac disease was diagnosed and folic acid deficiency documented. A gluten-free diet and a brief supplementation with folic acid lead to a complete EEG and clinical normalization in one case and to a significant improvement of EEG and seizure control in the other. PMID- 1908175 TI - Dynamic changes of myometrial activity, levels of PGF2 alpha and E2 in rabbits after insertion of four types of IUDs. AB - Myometrial activity, levels of PGF2 alpha and E2 in uterine flushings were measured in rabbits before and after insertion of four types of IUDs. The results showed that IUDs could increase the uterine contraction during the early stages of insertion. Thereafter, the uterine activity tended to be stable. The sequences of uterine contractility generally were: Cu-IUD greater than SS-IUD greater than LNG-Cu-IUD greater than LNG-IUD. The measurement of prostaglandins, determined by RIA, indicated that the concentrations of PGF2 alpha and E2 in Cu-IUD and SS-IUD groups were higher than those of controls for the early phase of insertion, which was not found after four months of use. Our results suggested that hyperactivity of the uterus in the early stage after insertion of IUDs might be relevant to side-effects like expulsion and pain. Copper released by Cu-IUD stimulates the uterine activity partially through increasing PGF2 alpha and E2 contents. In rabbits wearing LNG-IUD or LNG-Cu-IUD, both PGF2 alpha and E2 levels were low. The relatively low uterine mechanical and electrical activities were also observed in these two groups. Based on these data, it is concluded that development of LNG-Cu-IUD is feasible for reducing expulsion of IUDs. PMID- 1908174 TI - Inhibition of estrogen biosynthesis in the rat ovary by anordrin. AB - The delay in appearance of vaginal cornification associated with administration of anordiol (de-esterified anordrin) in the post-ovulatory period was confirmed. Ovarian tissue incubated in vitro for 2 h on the day which, in normal cycles, would be the day of proestrus produced negligible amounts of estradiol even in the presence of androstenedione and human menopausal gonadotropin, despite the appearance of apparently mature follicles in the ovaries. Ovaries of untreated rats produced significant amounts of estradiol when androstenedione was present. Continued incubation for 3 days resulted in significant estradiol production by ovaries of anordiol-pretreated rats in the presence of androstenedione, but less than that of ovaries of control rats. Granulosa cells of immature rats pretreated with diethylstilbestrol (DES) were unaffected by pretreatment with anordrin, whether anordrin was given before or after DES treatment. Taken together, the results indicate that anordiol inhibits development of the capacity for estrogen secretion in maturing follicles without affecting structural development, but that follicles that grow under the influence of high concentrations of estrogen (DES) are unaffected by the presence of anordrin (which is rapidly converted to anordiol in vivo). The latter result suggests that DES treatment bypasses the anordiol-sensitive step in follicular maturation. PMID- 1908176 TI - Management of IUD-associated menorrhagia in female rhesus monkeys (Macaca mulatta). AB - The study was undertaken to evaluate the effect of antifibrinolytic agents (epsilon-aminocaproic acid, EACA; tranexamic acid, AMCA), anti-inflammatory drugs (indomethacin, IND; ibuprofen, IBU; naproxen, NAP) and root extract of the plant Boerhaavia diffusa (BD) on menstrual cycle length (MCL), duration of menstrual flow (DMF), menstrual iron loss (MIL) and activity of uterine tissue plasminogen activator (tPA) in IUD-fitted monkeys. Premature onset of menstruation was observed in IUD-fitted monkeys (26.0 +/- 0.7 days, mean +/- SE) as compared to controls (28.7 +/- 0.4 days). No noteworthy change was observed in the MCL of drug treated monkeys as compared to IUD-fitted monkeys. An increase of 155%, 123.2%, and 288% was observed in the DMF, MIL and tPA activity after IUD insertion as compared to controls. Antifibrinolytic agents reduced the DMF, MIL and activity of tPA in IUD-fitted monkeys up to 117.4%, 116.4%, and 254%, whereas anti-inflammatory drugs caused a decrease only up to 69%, 95.1%, and 138%, respectively. Conclusively, root extract of B. diffusa treated IUD-fitted monkeys showed noticeable reduction in their DMF (124%), MIL (120.8%) and tPA activity (272%). PMID- 1908177 TI - Short-term and long-term effects of Norplant-2 on plasma lipoproteins and glucose tolerance. AB - Twenty-five women using the levonorgestrel-containing contraceptive implant, Norplant-2, were studied longitudinally, to see the effects on lipid profile, glucose tolerance and hepatic transaminases with short-term (12 weeks) and long term (18 to 24 months) use of Norplant-2 [corrected]. Total lipids, cholesterol, phospholipids, triglycerides and their subfractions were evaluated. There was a significant increase in LDL-cholesterol after 12 weeks of use (p less than 0.05), which did not persist at 18-24 months follow-up. The HDL-cholesterol, HDL/LDL cholesterol ratio, phospholipids, other lipid fractions, hepatic transaminases and glucose tolerance did not alter significantly following short-term or long term use of Norplant-2. PMID- 1908178 TI - Hormonal changes associated with bleeding during low dose progestogen contraception delivered by Norplant subdermal implants. AB - The main side effect associated with the use of Norplant contraceptive implants is a disruption of the menstrual bleeding pattern. To explore the relationship between bleeding and hormonal changes, we analyzed the estradiol (E2) and progesterone (P) patterns that preceded bleeding episodes or that corresponded to periods of amenorrhea in 103 cycles observed among 82 women using Norplant subdermal implants. Five different bleeding patterns were defined: 'normal' (24 45 day cycles), oligomenorrhea (46-90 day cycles), amenorrhea (over 90 day cycles), irregular/frequent bleeding (less than 25 day cycles), and prolonged bleeding (continuous bleeding/spotting for more than 10 days). All 'normal' cycles were associated with a rise followed by a fall in E2 levels preceding bleeding. In half of the 'normal' cycles (28/54), a rise and fall of P was also observed. The same pattern was found in oligomenorrheic cycles, but only two of 12 cycles had a rise and fall of both E2 and P. None of the subjects with amenorrhea had luteal activity. Six of the nine amenorrheic cycles displayed persistently low E2 levels (below 75 pg/ml). The remaining three had a moderate elevation in E2 levels during the sampling period. Sixty percent of the subjects who showed irregular/frequent bleeding (15/25) had low E2 levels (less than 75 pg/ml), without luteal activity, and bleeding occurred without clear evidence of a further drop in E2 levels. In the remaining 40%, bleeding was preceded by a rise and drop of E2 without luteal activity, with the exception of one women, who exhibited a rise and fall of both E2 and P. Samples were obtained in only three subjects during continuous bleeding. One had low E2 levels, and the remaining two bled continuously, in spite of having E2 levels in the normal range. We conclude that ovarian hormones continue to influence endometrial shedding during the use of Norplant contraceptive implants. PMID- 1908179 TI - Factors associated with the acceptance of Norplant or IUD among women with similar socio-demographic characteristics. AB - The purpose of this study was to identify factors that explain why women who consulted at the same clinic, went through the same counseling procedure and who had no contraindications for using Norplant decided to use another long-acting method, the IUD. Subjects were women who consulted at the Family Planning Clinic, State University of Campinas Hospital. One hundred Norplant acceptors and 100 IUD acceptors were interviewed at home, by trained interviewers who were not related to the clinic. Four out of five Norplant acceptors and all IUD acceptors had learned about the method chosen before attending the clinic. Results suggest that among IUD users there were more women who did not like the idea of taking a hormone or medicine to prevent pregnancy, while Norplant acceptors were more willing to try new experiences. Half the Norplant acceptors had learned about the method through TV, compared to 12% of IUD acceptors. Counseling at the clinic was not a determining factor, though it is important to clarify clients' doubts. PMID- 1908180 TI - Underutilization of thrombolytic therapy in eligible women with acute myocardial infarction. PMID- 1908181 TI - Effects of luminal eccentricity on spontaneous coronary vasoconstriction after successful percutaneous transluminal coronary angioplasty. PMID- 1908182 TI - Effects of sulfonylureas on adipocyte and skeletal muscle insulin action in patients with non-insulin-dependent diabetes mellitus. AB - The effect of glibenclamide treatment on insulin action in isolated fat cells was studied in eight moderately obese patients with non-insulin-dependent diabetes mellitus (NIDDM). Insulin receptor binding and the effect of insulin on glucose transport and lipogenesis were determined before and after 3 months of glibenclamide therapy. At the end of the treatment period, mean daytime plasma glucose concentrations were reduced (10.8 +/- 0.4 versus 7.0 +/- 0.3 mmol/L, p less than 0.001) whereas mean daytime plasma insulin level was increased (40 +/- 12 versus 71 +/- 9 mU/L, p less than 0.001). Adipocyte insulin receptor binding as well as basal glucose transport and metabolism were unaffected by drug treatment. In contrast, insulin-stimulated glucose transport and lipogenesis were both significantly enhanced (p less than 0.05). These findings are comparable to those of another study involving seven moderately obese subjects with NIDDM who had biopsies of the lateral vastus muscle taken for measurement of insulin receptor function and glycogen synthase activity before and during 2 months of gliclazide treatment. In that study insulin receptors purified with wheatgerm agglutinin showed unchanged insulin binding and receptor kinase activity. Moreover, gliclazide had no impact on maximal glycogen synthase activity. However, under physiologic hyperinsulinemic conditions gliclazide therapy was associated with an increased sensitivity of glycogen synthase for its allosteric activation by glucose-6-phosphatase (p less than 0.04). In conclusion, sulfonylurea treatment of NIDDM enhances insulin-stimulated peripheral glucose utilization in part through a potentiation of insulin action on adipose tissue glucose transport and lipogenesis and skeletal muscle glycogen synthase. PMID- 1908183 TI - Increased fibrinolytic potential induced by gliclazide in types I and II diabetic patients. AB - This study examined the effect of gliclazide on tissue-type plasminogen activator (t-PA)-related fibrinolysis in 23 Type I diabetic patients without residual beta cell function and 17 Type II diabetic patients initially treated with tolbutamide. The Type I diabetic patients received gliclazide for a period of 6 months; the Type II diabetic patients were shifted from tolbutamide to gliclazide. In Type I diabetic patients, after 2-3 months of treatment with gliclazide, we observed a significant increase in plasma concentrations of total t-PA antigen that remained stable until discontinuation of the drug (p less than 0.0002), whereas the plasma concentrations of plasminogen activator inhibitor (PAI) did not change significantly during the study. Next, we investigated the possibility of gliclazide inducing t-PA-related fibrinolysis in a subset of Type II diabetics without detectable concentrations of t-PA during treatment with tolbutamide. The concentrations of active t-PA increased significantly 3 months after a change in treatment to gliclazide, and active t-PA again decreased in one patient to undetectable levels after 12 months with gliclazide. Moreover, the plasma concentrations of total t-PA antigen increased significantly (p less than 0.02) in this group of diabetic patients while PAI remained unchanged. The changes in t-PA-related fibrinolysis could not be related in either Type I or Type II diabetics to changes in metabolic state evaluated by blood glucose, HbA1c, cholesterol, triglycerides, or apolipoproteins A and B. We conclude that gliclazide has the potential to exert extrametabolic non-insulin-mediated effects on t-PA-related fibrinolysis in diabetic patients. PMID- 1908184 TI - The gliclazide poster world in Lisbon, 1989. PMID- 1908185 TI - Enhanced sensitization after cordocentesis in a rhesus-isoimmunized pregnancy. AB - It has been suggested that the optical density at 450 nm may be an unreliable predictor of the severity of fetal anemia in the midtrimester of pregnancy; therefore fetal blood sampling, rather than amniotic fluid evaluation, should be performed in all isoimmunized pregnancies with elevated maternal antibody titers in the midtrimester. Potential complications of such an approach are discussed and an alternative plan of management is offered. PMID- 1908186 TI - Two cationic amino acid transport systems in human placental basal plasma membranes. AB - Transport of cationic amino acids in basal (fetal facing) plasma membranes was investigated by characterization of L-[3H]lysine and L-[3H]arginine uptake in membrane vesicles isolated from term human placentas. At least two Na(+) independent systems were present. Lysine concentration dependence data were fit by a two-system model with Km values of 1.0 +/- 0.8 and 223 +/- 57 microM and Vmax values of 0.06 +/- 0.03 and 24.0 +/- 5.8 pmol.mg protein-1.min-1. In the presence of either 10 mM L-leucine or Na+ plus 10 mM L-homoserine, the data were fit by single system models with kinetic parameters similar to the higher and lower Km systems seen in the absence of inhibitors. Uptake of 10 or 20 microM L lysine in the absence of Na+ showed the higher Km system was inhibited completely by L-arginine, L-homoarginine, and L-histidine. In the presence of Na+, the higher Km system was inhibited completely by L-alanine, L-homoserine, L-leucine, L-phenylalanine, and L-norleucine. The lower Km system was inhibited completely by L-arginine, L-homoarginine, L-histidine, L-leucine, and L-methionine. Time course studies of uptake demonstrated that uptake by either system alone filled the total vesicular space. The basal membrane of human placental syncytiotrophoblast possesses two transport systems for lysine and arginine, resembling the ubiquitous y+ system and the bo,+ system previously described in mouse blastocysts. The higher Vmax of the y+ system suggests that in utero it may mediate transfer of cationic amino acids from the syncytiotrophoblast to the fetus. The role of the high-affinity low-capacity bo,+ system remains to be determined. PMID- 1908187 TI - Adenine nucleotide synthesis in exercising and endurance-trained skeletal muscle. AB - Strenuous exercise leads to increased efflux of purine nucleoside and base that should necessitate recovery of adenine nucleotides by either the de novo synthesis or salvage pathway. De novo synthesis of adenine nucleotide was measured in quiescent and contracting muscle of sedentary and exercise-trained rats using an isolated perfused hindquarter preparation. Synthesis rates were assessed by measuring the incorporation of [1-14C]glycine into adenine nucleotide in muscles of both resting and stimulated hindlimbs after 1 h of either low- or high-energy demand isometric contractions. In nonstimulated sedentary and trained muscles, rates of de novo synthesis were similar. The effect of muscle contractions on de novo synthesis varied among muscle fiber types. Contracting, nonfatigued fast-twitch muscle sections showed significant declines in de novo synthesis in both sedentary and trained groups. Rates in slow-twitch red fibers and fatigued fast-twitch white fiber sections were not different from rest. Supplementing the perfusate with 5 mM ribose caused de novo synthesis to rise three- to fourfold in each of the fiber sections. However, the response in synthesis rates due to exercise was similar with or without ribose supplementation. De novo synthesis does not increase during exercise but exhibits an unchanged or reduced rate depending on the expected energy balance within the cell. This would occur if the energy state of muscle exerts significant control over de novo synthesis of adenine nucleotide. PMID- 1908188 TI - Effects of extracellular pH, CO2, and HCO3- on ketogenesis in perfused rat liver. AB - Effects of extracellular pH, CO2, and HCO3- on ketone body production from octanoate were studied in perfused livers from fasted rats. pH was adjusted to 7.1-7.5 by varying perfusate [HCO3-] and [CO2], where brackets denote concentration. At constant 25 mM [HCO3-], total production of beta hydroxybutyrate (beta-OHB) + acetoacetate (AcAc) was constant from pH 7.1 to 7.5. However, the [beta-OHB]/[AcAc] ratio decreased from 1.60 to 1.00 when pH decreased from 7.3 to 7.1; there was no change at pH 7.4. At constant [CO2], decreasing pH from 7.4 to 7.1 did not alter either total ketogenesis or the [beta OHB]/[AcAc] ratio. This suggests that high [CO2] rather than low pH was responsible for the alteration in the redox ratio. At constant pH of 7.4, variations in [HCO3-] between 15 and 25 mM did not influence total ketogenesis or the [beta-OHB]/[AcAc] ratio. However, increasing [HCO3-] from 25 to 35 mM decreased the [beta-OHB]/[AcAc] ratio from 1.76 to approximately 1, again without affecting total ketogenesis. At constant 1.75 mM [CO2], increasing [HCO3-] from 25 to 35 mM also reduced the [beta-OHB]/[AcAc] ratio from 1.63 to approximately 1, suggesting that the effect of high [HCO3-] on this redox ratio can be ascribed to HCO3- itself. It is concluded that high [CO2] or [HCO3-] decreases the mitochondrial [NADH]/[NAD+] ratio in hepatocytes, resulting in a decreased [beta OHB]/[AcAc] ratio. PMID- 1908189 TI - Misoprostol attenuates acetic acid-induced increases in mucosal permeability and inflammation: role of blood flow. AB - The objectives of this study were 1) to quantify the effects of misoprostol (Miso; prostaglandin E1 analogue) on acetic acid-induced increases in mucosal permeability and inflammation; 2) to determine what effect acetic acid, Miso, or the combination of Miso plus acetic acid has on colonic blood flow; and 3) to assess whether the protective effect of Miso may be attributable to its vasodilatory properties. We found that intrarectal administration of acetic acid produced a 6.4-fold increase in colonic myeloperoxidase activity (an index of granulocyte infiltration), an 8.2-fold increase in mucosal permeability, a 1.6 fold increase in colonic weight, and a 6.8% decrease in body weight 48 h after enema. Miso pretreatment significantly attenuated the increases in colonic myeloperoxidase activity, mucosal permeability, and colon weight as well as prevented the loss of body weight. In a different series of experiments, we found that blood flow in the descending, transverse, and ascending colon increased 2.5- to 3.5-fold immediately after the acetic acid enema; however, it returned to control values at 1 and 4 h after enema. Miso pretreatment, followed by acetic acid, resulted in a further increase (2.5-fold) in blood flow in the descending colon 1 h after enema compared with acetic acid alone. This Miso-induced increase in blood flow at 1 h could not account for its protective effect inasmuch as colonic mucosal permeability (i.e., injury) in Miso-pretreated animals was not significantly different from values obtained in animals pretreated with vehicle and then given the enema. PMID- 1908191 TI - Monitoring of tidal carbon dioxide in spontaneously breathing patients using a mainstream analysing monitor. PMID- 1908190 TI - Acupuncture and transcutaneous stimulation analgesia in comparison with moderate dose fentanyl anaesthesia in major surgery. Clinical efficacy and influence on recovery and morbidity. AB - The efficacy of acupuncture and transcutaneous stimulation analgesia, supplemented by small doses of fentanyl (mean 1.2 micrograms/kg, SD 1.7) was compared with moderate-dose fentanyl anaesthesia (mean 22.9 micrograms/kg, SD 2.8) in 29 patients who underwent surgery for retroperitoneal lymph node dissection. The present study describes the anaesthetic techniques and comparison of haemodynamics, demand for analgesics after surgery, recovery and blood gases, restoration of urinary and bowel functions, convalescence in terms of self reliance and the postoperative course in respect of fatigue and morbidity. A more rapid return of consciousness, an absence of hypercapnia and a smaller decrease in pH were observed in patients who received acupuncture and transcutaneous stimulation (p less than 0.05). No clinically relevant disadvantages attributable to the method were demonstrated. PMID- 1908192 TI - Lumbar epidural diamorphine following thoracic surgery. A comparison of infusion and bolus administration. AB - Twenty-two patients received a single dose of diamorphine 5 mg through a lumbar epidural catheter before thoracic surgery. The patients were transferred after surgery to a high dependency unit where they were allocated randomly to receive either an infusion of epidural diamorphine at a rate of 1 mg/hour (group 1) or bolus doses of epidural diamorphine 5 mg on demand (group 2). There was no statistically significant difference between the groups in visual analogue pain scores in the first 18 postoperative hours. Arterial carbon dioxide tension was elevated in both groups and was consistently higher in group 1 than in group 2, with a statistically significant intergroup difference 12 hours after operation. Respiratory rate was not a useful index of respiratory depression. The commonest nonrespiratory side effect was urinary retention, but the incidences of this and other minor side effects were similar in the two groups. PMID- 1908193 TI - Assessment of threonine metabolism in vivo by gas chromatography/mass spectrometry and stable isotope infusion. AB - The fractional contributions (FC) of threonine to glycine and 2-ketobutyrate (KB) fluxes in fed pigs have been assessed by the constant infusion of L-[1-13C] threonine. The analysis of the enantiomeric purity of labeled threonine by gas chromatography/mass spectrometric (GC/MS) analysis is reported as the N-TFA isopropyl ester derivative. The commercially available [1-13C]threonine comprised 98.7% of the L-enantiomer, enriched at 99 atom percentage excess (APE), and 1.3% of L-allo-threonine contaminant, also enriched at 99 APE. The enantiomeric purity of threonine in plasma of pigs infused for 10 h with [1-13C]threonine showed that the L-allo contaminant did not accumulate. The t-butyl dimethylsilyl derivatives of threonine, glycine, and 2-aminobutyrate (ABA) were used to measure the enrichment of these compounds in plasma and liver samples by GC/MS/selected ion monitoring analysis. Analyses were performed on between 1 and 5 nmol of each amino acid extracted from biological fluids and a 1:10 split injection. GC/MS parameters were assessed with standards at similar quantities and found to be satisfactory; e.g., injection of 1-10 nmol of glycine did not significantly alter the slope and the precision of the standard curve. The coefficient of variation of enrichment determination was less than 10% for standards enriched at 0.4 APE or more and biological samples enriched at 0.6 APE or greater. Within-animal coefficients of variation for four plasma samples obtained at equal intervals between 8 and 10 h of [1-13C]threonine infusion were 4, 21, and 24% for threonine, ABA, and glycine, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1908195 TI - Direct stimulation of poly(ADP ribose) polymerase in permeabilized cells by double-stranded DNA oligomers. AB - Poly(ADP ribosyl)ation, a post-translational modification of nuclear proteins catalyzed by poly (ADP ribose) polymerase, is an immediate response of most eukaryotic cells to DNA strand breaks and has been implicated in DNA repair and other cellular phenomena associated with DNA strand breakage. Poly(ADP ribose) polymerase activity levels have been frequently assayed by incubating permeabilized cells with radioactively labeled NAD+ as substrate. In such assays enzyme activation has routinely been achieved indirectly by prior exposure of living cells to carcinogens or by adding DNase I to permeabilized cells, thereby introducing strand breaks in chromosomal DNA. Here we show that, as an alternative method, the direct activation of purified poly(ADP ribose) polymerase by double-stranded oligonucleotides (N. A. Berger and S. I. Petzold, 1985, Biochemistry 24, 4352-4355) can be adopted for permeabilized cell systems. The inclusion of a palindromic decameric deoxynucleotide in the reaction buffer stimulated the enzyme activity in permeabilized Molt-3 human lymphoma cells up to 30-fold (at 50 micrograms/ml [corrected] oligonucleotide concentration) in a concentration-dependent manner. The activating effect of oligonucleotides was also evident when ethanol-fixed HeLa cells were postincubated with NAD+ to allow poly(ADP ribose) synthesis to occur in situ, which was detected as specific anti poly (ADP ribose) immunofluorescence. We conclude that double-stranded oligonucleotides can be conveniently used as chemically and stoichiometrically well-defined poly (ADP ribose) polymerase activators in permeabilized or ethanol fixed mammalian cells. PMID- 1908194 TI - Quantitative analysis of polymerase chain reaction (PCR) products using primers labeled with biotin and a fluorescent dye. AB - PCR primers covalently labeled with biotin and a fluorescent dye allow immobilization and separation of the products which can be quantitatively analyzed subsequently. The procedure we have developed circumvents electrophoretic separation and radioactive labeling. Exact quantitative analysis of reaction products is feasible during the logarithmic phase of amplification when Taq polymerase is not limiting, as it is during the plateau phase of the reaction. With appropriate standardization the procedure can be used for routine diagnostic purposes. PMID- 1908196 TI - Novel trifunctional carrier molecule for the fluorescent labeling of haptens. AB - We developed a novel trifunctional carrier molecule for the synthesis of hapten fluorophore conjugates as reporter molecules in immunoassays. This carrier eliminates some of the disadvantages associated with currently used fluorophore labeling procedures including high nonspecific binding. The backbone of the carrier consists of the 21 amino acid residues of the insulin A-chain molecule. This polypeptide provides a single site (terminal amino group) for covalent coupling of the hapten, three carboxyl groups for the attachment of fluorophores, and four sulfhydryl groups for derivatization with hydrophilic residues to compensate for the hydrophobic effect of the attached fluorophores. The sites for fluorophore attachment are 4, 17, and 21 amino acids away from the hapten attachment site. This spatial separation minimizes quenching of the fluorescence signal due to interaction of the fluorophores with each other and with the attached hapten. In this study, 2,4-dinitrophenol (DNP) was selected as model hapten, fluorescein as label, and S-sulfonate groups as hydrophilic residues. The properties of the DNP-insulin A-chain-fluorescein conjugate (DNP-Ins-Fl) were compared to those of a DNP derivative labeled with a single fluorescein moiety via a small lysine spacer (DNP-Lys-Fl). The DNP-Ins-Fl conjugate exhibited a 3 fold lower nonspecific adsorption to immobilized non-immune IgG contributing to an approximately 3-fold more efficient displacement from the binding sites of an immobilized monoclonal anti-DNP antibody by the antigen DNP-lysine. Furthermore, at equimolar concentrations the DNP-Ins-Fl generated a 2.6-fold higher fluorescent signal than DNP-Lys-Fl.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1908197 TI - Selective removal of molybdenum traces from growth media of N2-fixing bacteria. AB - A new method for the selective removal of traces of molybdenum from growth media of N2-fixing bacteria (Rhodobacter capsulatus and Klebsiella pneumoniae) was developed. This method is based on the filtration of nutrient solutions through a layer of activated carbon (pulverized charcoal). The adsorption of Mo (molybdate) to activated carbon was optimal if a charcoal suspension (50 g/liter) was degassed by boiling before use and if the pH of the solutions, which had to be purified, was adjusted to values between 1.5 and 4. In this pH region no or only negligible amounts of other metal ions were adsorbed. The activated carbon method was compared with other Mo-eliminating procedures, including 8 hydroxyquinoline/dichloromethane extraction, Chelex 100 chromatography, and treatment with Mo-starved Azotobacter vinelandii cells. The activated carbon filtration appeared to be the most effective, specific, and rapid method. Whereas the untreated Rhodobacter growth medium was contaminated with 1.2 ppb Mo, as analyzed by inductively coupled plasma mass spectrometry (ICP-MS), the activated carbon-treated medium was below the ICP-MS detection limit (less than 0.05 ppb). A similarly effective removal of Mo impurities was obtained by the Azotobacter treatment. Even at low optical densities (2-5 at 436 nm) Mo traces were removed very rapidly within 10-15 min. However, because the Mo uptake/Mo adsorption capacity of A. vinelandii depended on freshly cultivated cells and on the growth phase at which the cells were harvested, this microbiological method was generally more time-consuming and less reproducible than the activated carbon method.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1908198 TI - Methicillin-resistant Staphylococcus aureus: colonization and infection in a long term care facility. AB - OBJECTIVE: To assess methicillin-resistant Staphylococcus aureus (MRSA) colonization, transmission, and infection over a 1-year period in a long-term care facility with endemic MRSA. DESIGN: Monthly surveillance for MRSA colonization of nares, perineum, rectum, and wounds. SETTING: Long-term care facility attached to an acute care Veterans Affairs medical center. PATIENTS: All 341 patients in the facility had monthly surveillance cultures for 1 year. OUTCOME MEASUREMENTS: Colonization and infection with MRSA. MAIN RESULTS: The monthly MRSA colonization rate was 23% +/- 1.0%; colonization occurred most commonly in the nares and wounds. Poor functional status was associated with MRSA colonization. Most patients (65%) never acquired MRSA; 25% of patients were already colonized at admission to the facility or at the start of the study, and only 10% of newly admitted patients acquired MRSA while in the facility. These latter patients acquired several different strains in a pattern of acquisition similar to that generally seen within the facility. In the course of 1 year, only nine patients who acquired MRSA had a roommate with the same phage type; no clustering was evident, and none of these patients developed infection. Nine other patients (3%) developed MRSA infection; five of these patients required hospitalization, but none died as a result of infection. CONCLUSIONS: In the long term care facility in which our study took place, MRSA was endemic, and the infection rate was low. In such settings, the cost effectiveness of aggressive management of MRSA (widespread screening for MRSA and eradication with antimicrobial agents) needs to be assessed. PMID- 1908200 TI - Oral ofloxacin therapy for invasive external otitis. AB - The clinical efficacy and safety of orally administered ofloxacin (400 mg twice daily) were evaluated in 24 adult patients (17 men and 7 women; mean age, 65.8 years) with pseudomonal invasive external otitis (IEO). The patients were divided into two groups: group A, (n = 9) suffering from a mild form of IEO, and group B (n = 15), suffering from a more severe form of the disease. Diabetes mellitus was the main underlying disease in these patients. Pseudomonas aeruginosa was the only pathogen in 18 infected ears and part of the polymicrobial flora in an additional 6. Cure was observed in 83.3% of the patients. Two of the cured patients required more than one course of ofloxacin treatment. Development of P aeruginosa resistant to ofloxacin (n = 3) and severe allergic reaction (n = 1) required the discontinuation of ofloxacin therapy. Other side effects such as nausea, arthralgia, and vaginal itching were minimal. Oral administration of ofloxacin seems to be an effective, convenient, relatively safe, and economical therapy of IEO caused by the susceptible organism. PMID- 1908201 TI - Immunohistochemical localization of spleen-type prostaglandin D synthetase in rat nasal mucosa. AB - Using the specific antibody of spleen-type prostaglandin D synthetase, we investigated the immunohistochemical localization of this enzyme in rat nasal mucosa. The excised tissues were fixed with 4% paraformaldehyde and immunohistochemically stained by the peroxidase-antiperoxidase method. Formalin resistant connective tissue mast cells were positive for spleen-type prostaglandin D synthetase. PMID- 1908199 TI - Nasopharyngeal flora in the first three years of life in normal and otitis-prone children. AB - Nasopharyngeal carriage of the three major middle ear pathogens (Streptococcus pneumoniae, nontypeable Hemophilus influenzae, and Moraxella catarrhalis) was evaluated prospectively in a group of 110 children followed up for the first 3 years of life. The findings suggested that nasopharyngeal carriage of middle ear pathogens increases significantly during respiratory illness among the general population of young children; however, otitis-prone children demonstrated a tendency to carry nontypeable H influenzae at an unusually high rate even during health. This propensity to carry nontypeable H influenzae might explain why nontypeable H influenzae is a major cause of recurrent or chronic otitis media. PMID- 1908202 TI - Linoleic acid chyloportal partition and metabolism during its intestinal absorption. AB - 1-14C linoleic acid intestinal absorption and simultaneous biochemical events were followed up on rats under vascular perfusion and on main mesenteric lymphatic duct fistulated rats. 1-14C linoleic acid was introduced in the duodenum alone in doses from 1.2 to 90 mumol or in the presence of oleic acid and monopalmitin (30/30/30 mumol/mumol/mumol). Mesenteric portal venous blood and chyle, respectively, were collected continuously for 1 and 6 h after the infusions. Blood-labeled lipid recovery varied from 4.7 to 2.2% of the 14C linoleic acid infused as the 14C linoleic acid dose infused increased, and dropped to 1.8% with the mixed lipid infusate. Lymph-labeled lipid recovery increased from 25.7 to 31.8% of the 14C linoleic acid infused as the dose infused increased, and rose to 48.1% with the mixed lipid infusate. The oxidation of 1 14C linoleic acid remained low: 0.8-3% of the infused radioactivity. A desaturation and elongation of 14C linoleic acid into 14C arachidonic acid was detected and discussed. We can conclude that the linoleic lymph absorption pathway remained preferential in our experimental conditions, simultaneous to a low rate of oxidation and an eventual ability for the enterocyte to convert this essential fatty acid arachidonic acid. PMID- 1908204 TI - Typing of human, animal, food, and environmental isolates of Listeria monocytogenes by multilocus enzyme electrophoresis. AB - In order to elucidate some aspects of the epidemiology of listeriosis in Switzerland, 181 strains of Listeria monocytogenes isolated from humans, animals, food, and the environment have been analyzed by multilocus enzyme electrophoresis at 21 enzyme loci. The clone responsible for several recent food-borne outbreaks in Switzerland and in North America (marked by electrophoretic type 1 and serovar 4b) has been found frequently among strains isolated from animals. Thus, animals may represent a major source of diffusion of this clone in the environment and in food, in which it has been found only sporadically, however. Two other unrelated clones (including strains belonging to serovars 1/2b and 1/2c) have often been isolated from meat but not from animals. These findings indicate that contamination of meat with L. monocytogenes might originate mainly from the environment in which it is processed rather than from animals themselves. This could explain the differences in the distribution of L. monocytogenes serovars isolated from meat and from animals. PMID- 1908205 TI - Methanogenic bacteria as endosymbionts of the ciliate Nyctotherus ovalis in the cockroach hindgut. AB - Production of methane in the hindgut of the cockroach Periplaneta americana was found to vary, depending on the feeding regimen. Methane production was positively correlated with the numbers of the ciliate Nyctotherus ovalis living in the cockroach hindgut. Defaunation of the cockroaches by means of low concentrations of metronidazole (Flagyl) resulted in a quick drop of methane production. Addition of the methanogenic substrates acetate and formate to isolated hindguts stimulated methane production. Inside the ciliate cells, autofluorescing bacteria could be demonstrated which were presumed to be methanogens. Electron microscopy revealed that the bacteria resembled Methanobrevibacter and that they were closely associated with organelles which contained infolded membranes and which were presumably hydrogenosomes. PMID- 1908203 TI - Rapid confirmation of Listeria monocytogenes isolated from foods by a colony blot assay using a digoxigenin-labeled synthetic oligonucleotide probe. AB - An oligodeoxyribonucleotide probe based on the sequence of a 321-bp internal fragment of the msp gene encoding a major secreted polypeptide of Listeria monocytogenes was labeled with digoxigenin by using terminal deoxynucleotidyl transferase. The specificity of the digoxigenin-labeled probe was determined by dot blot assays. The probe reacted with all strains of L. monocytogenes tested (12 of 12 strains representing five serotypes). The probe did not react with any other Listeria species or with other gram-positive bacteria (Brochothrix, Erysipelothrix, Corynebacterium, Rhodococcus, Lactobacillus, Leuconostoc, Bacillus, Staphylococcus, and Streptococcus). The probe was used to develop a colony blot assay for the rapid confirmation of L. monocytogenes on Listeria selective agars which had been streaked with food enrichment cultures. Forty eight food samples were tested by conventional culture and DNA colony blot assay. The sensitivity and specificity of the DNA colony blot were 100 and 97%, respectively. PMID- 1908206 TI - Role of flagella in adhesion of Pseudomonas fluorescens to tendon slices. AB - Tendon slices were used as model surfaces to investigate the role of flagella in the adhesion of Pseudomonas fluorescens to meat. The slices were introduced into a specially designed flow chamber, which was then filled with a suspension of the organism, and the tendon surface was observed at a x640 magnification. The same events that occur during the colonization of glass surfaces (apical adhesion of cells with rotation around the contact point, longitudinal adhesion, detachment of apically and longitudinally adherent cells) were also observed on tendon. Mechanical removal of the flagella resulted in no change in the contact angles with 0.1 M saline or alpha-bromonaphthalene, in the electrophoretic mobility, or in the adhesion of the organism to hydrophobic and ion-exchange resins. In addition, cells from which flagella had been mechanically removed still adhered extensively to tendon. Nevertheless, under comparable conditions (bacterial concentration, contact time), flagellated cells adhered to tendon in larger numbers than did deflagellated cells. This was entirely due to the ability of the motile flagellated cells to reach tendon in greater numbers than deflagellated cells. PMID- 1908207 TI - Bioluminescence assay for estimating the hydrophobic properties of bacteria as revealed by hydrophobic interaction chromatography. AB - The luciferin-luciferase bioluminescence method was used to estimate the number of bacteria retained in neutral and amphiphilic gels and those in the eluate to determine the hydrophobic surface properties of bacteria by using hydrophobic interaction chromatography. Good correlations were found between viable counts and ATP content for Escherichia coli, Pseudomonas fragi, and Listeria monocytogenes. ATP determination was more rapid than viable counts for characterizing the relative hydrophobicity of L. monocytogenes. Quantitative estimations of adsorption of L. monocytogenes on octyl-Sepharose indicate that this microorganism is hydrophilic. PMID- 1908209 TI - Inhibition of food-borne bacterial pathogens by bacteriocins from lactic acid bacteria isolated from meat. AB - Ten strains of bacteriocin-producing lactic acid bacteria were isolated from retail cuts of meat. These 10 strains along with 11 other bacteriocin-producing lactic acid bacteria were tested for inhibitory activity against psychotrophic pathogens, including four strains of Listeria monocytogenes, two strains of Aeromonas hydrophila, and two strains of Staphylococcus aureus. Inhibition due to acid, hydrogen peroxide, and lytic bacteriophage were excluded. The proteinaceous nature of the inhibitory substance was confirmed by demonstration of its sensitivity to proteolytic enzymes. Eight of the meat isolates had inhibitory activity against all four L. monocytogenes strains. Bacteriocin activity against L. monocytogenes was found in all of the strains obtained from other sources. Activity against A. hydrophila and S. aureus was also common. PMID- 1908208 TI - Factors influencing inclusion body formation in the production of a fused protein in Escherichia coli. AB - Different parameters that influenced the formation of inclusion bodies in Escherichia coli during production of a fused protein consisting of protein A from Staphylococcus aureus and beta-galactosidase from E. coli were examined. The intracellular expression of the fused protein was controlled by the pR promoter and its temperature-sensitive repressor. The induction temperature, the pH of the cultivation medium, and changes in the amino acid sequence in the linker region between protein A and beta-galactosidase had a profound effect on the formation of inclusion bodies. At 42 degrees C, inclusion bodies were formed only during the first hours after induction, and thereafter all the recombinant protein that was further produced appeared in a soluble and active state. Production at 39 and 44 degrees C resulted in inclusion body formation throughout the production period with 15 to 20% of the produced recombinant protein appearing as inclusion bodies. Cultivating cells without control of pH caused inclusion body formation throughout the induction period, and inclusion body formation increased with decreasing pH, and at least part of the insoluble protein was formed from the pool of soluble fusion protein within the cell. Changes in the amino acid sequence in the linker region between the two parts of the fusion protein abolished inclusion body formation. PMID- 1908211 TI - Inhibition of trichloroethylene oxidation by the transformation intermediate carbon monoxide. AB - Inhibition of trichloroethylene (TCE) oxidation by the transformation intermediate carbon monoxide (CO) was evaluated with the aquifer methanotroph Methylomonas sp. strain MM2. CO was a TCE transformation intermediate. During TCE oxidation, approximately 9 mol% of the TCE was transformed to CO. CO was oxidized by Methylomonas sp. strain MM2, and when formate was provided as an electron donor, the CO oxidation rate doubled. The rate of CO oxidation without formate was 4.6 liter mg (dry weight)-1 day-1, and the rate with formate was 10.2 liter mg (dry weight)-1 day-1. CO inhibited TCE oxidation, both by exerting a demand for reductant and through competitive inhibition. The Ki for CO inhibition of TCE oxidation, 4.2 microM, was much less than the Ki for methane inhibition of TCE oxidation, 116 microM. CO also inhibited methane oxidation, and the degree of inhibition increased with increasing CO concentration. When CO was present, formate amendment was necessary for methane oxidation to occur and both substrates were simultaneously oxidized. CO at a concentration greater than that used in the inhibition studies was not toxic to Methylomonas sp. strain MM2. PMID- 1908210 TI - Isolation and characterization of a lipolytic bacterium capable of growing in a low-water-content oil-water emulsion. AB - A unique lipolytic bacterium was isolated in a selective growth system consisting of 99% triglycerides and a 1% water phase. The bacterium, termed Pseudomonas aeruginosa YS-7, was able to grow in an environment of low water content and could also survive amphipathic, osmotic, and matrical water stress in a triglyceride-rich culture. The isolated strain was identified as P. aeruginosa on the basis of standard physiological, biochemical, and serological assays. The strain is a gram-negative motile rod, aerobic, pigment forming, and capable of growing at 42 degrees C. It is highly tolerant of high concentrations of the cationic detergent cetyltrimethylammonium bromide and of the fatty acid salts derived from bacterial hydrolysis of the oil. Growth of the bacterium in a pure culture in a 99% triglyceride medium lasted until most of the water was evaporated or consumed. Growth was accompanied by triglyceride hydrolysis, which continued to occur even after growth saturation until the water was totally depleted. No loss of viability was observed when the culture was maintained under water-depleted conditions for an additional 40 h. A second cycle of bacterial growth and triglyceride hydrolysis was immediately initiated upon the addition of 1% (vol/vol) water to the culture. Lipase activity was stable regardless of changes in culture conditions. The isolated strain is uniquely resistant to severe water stress in a triglyceride-rich medium or under cold acetone precipitation compared with 12 other microbial strains, including bacteria and yeasts. Among these 12, only the lipolytic strains grew in the 99% triglyceride medium, but they reached a cell mass fourfold smaller than that of P. aeruginosa YS-7.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1908212 TI - [Sensitivity test of anti-tumor agents. 2. Application of MTT assay]. AB - Mosmann's method for measuring the number of viable cells, examination of their growth and function by tetrazolium test, "MTT assay", is widely thought to be reliable. For the purpose to establish a rapid, accurate, in vitro drug sensitivity test, MTT assay was applied and evaluated for clinical application. Based on Mosmann's original MTT assay, optimal and adequate conditions for (1) the number of the cells examined at the starting of cultivation, (2) concentration of anti-tumor agents, doxorubicin, cisplatin, mitomycin C, L phenylalanine mustard, (3) incubation time with anti-tumor agents, were determined using established cell lines, T-24, RMUG, HeLa, Vero, P 388, and Colon 26 in 96 well microplates. Conclusions are as below: (1) Number of the cells in each well of microplate is 1 x 10(3)-1 x 10(6) cells/ml, that seemed to be theoretically and technically adequate. (2) Anti-tumor agents should be added at the peak plasma concentration. (3) Incubation for 4 to 5 days is preferable. (4) HCl-isopropanol seemed to be advantageous compared to 10% sodium dodecyl sulfate for solubilization of MTT formazan crystal. (5) Results of MTT assay and colony assay were well correlated. PMID- 1908213 TI - [Chemosensitivity test for gastric cancer by in vitro MTT assay]. AB - In vitro MTT assay was applied for examining chemosensitivity with 104 samples; 56 primary tumors, 31 lymph node, 9 liver, and 8 peritoneal metastases, obtained from 87 patients with advanced gastric carcinoma. The rate of effectiveness of various anticancer drugs were as follows; etoposide, 87.7%; cisplatin, 55.1%; mitomycin C, 51.5%; pirarubicin, 50.0%; aclarubicin, 48.8%; carboquone, 31.8%; doxorubicin, 20.3%; and 5-fluorouracil, 12.9%. Etoposide was found to be most effective against gastric carcinoma in this test. Concerning with the metastatic lesions, liver metastases were resistant to all tested drugs. On the other hand, peritoneal metastases were sensitive to etoposide, mitomycin C, and pirarubicin. The results indicate heterogeneity of the chemosensitivity between primary and metastatic lesions, and it was supposed that etoposide might be useful against human gastric cancer. PMID- 1908214 TI - [A long-term survival case of advanced gastric cancer undergoing radical gastrectomy by second-look operation after successful chemotherapy (CDDP, MMC, 5 FU)]. AB - A 55-year-old woman with gastric cancer underwent laparotomy and was found to have an unresectable tumor characterized by S3 (invasion of the pancreas), N3, P0 and H0. She was then treated by combined administration of cisplatinum, mitomycin C and 5-fluorouracil. A remarkable response (CR) was confirmed by upper gastrointestinal roentgenography and endoscopy. Upon reoperation about 8 weeks after chemotherapy, a successful radical total gastrectomy with R2 (partially R3) lymphnode dissection was performed. Histological examination of the specimens, including the stomach and lymphnodes, revealed no cancer cells in any region (pCR). She had been given UFT and PSK for 4 years 4 months after reoperation. She has lived for 5 years 2 months after reoperation without any signs of recurrence or metastases. PMID- 1908215 TI - Legal myths about terminating life support. AB - There are a number of myths about what the law permits concerning the termination of life support, some of which spring from a fundamental misconception of what law is. A serious misunderstanding of the law can lead to tragic results for physicians, health care institutions, patients, and families. These misunderstandings are (1) anything that is not specifically permitted by law is prohibited; (2) termination of life support is murder or suicide; (3) a patient must be terminally ill for life support to be stopped; (4) it is permissible to terminate extraordinary treatments, but not ordinary ones; (5) it is permissible to withhold treatment, but once started, it must be continued; (6) stopping tube feeding is legally different from stopping other treatments; (7) termination of life support requires going to court; and (8) living wills are not legal. PMID- 1908216 TI - Renal colic. Utility of the plain abdominal roentgenogram. AB - We conducted a retrospective cohort study of 85 consecutive symptomatic patients to evaluate the sensitivity, specificity, and predictive value of plain abdominal roentgenography (PAR) compared with clinical evaluation alone in diagnosis and treatment of renal colic. With a positive intravenous pyelogram and/or actual stone retrieval used as the gold standard, 72 patients had documented stones. The calculated sensitivity and specificity for PAR were 58% (95% confidence interval, 47% to 69%) and 69% (95% confidence interval, 44% to 94%), respectively. In this population with a stone prevalence of 85%, the positive predictive value of PAR was 91%. A clinical scoring system based on signs and symptoms fared as well as PAR (sensitivity, 73%; specificity, 46%; and positive predictive value, 88%). The strategy of clinical scoring followed by selective use of intravenous pyelography was more cost-effective than strategies using PAR. We conclude that the PAR has low sensitivity and specificity and improves the predictive value only marginally, and its routine use is not cost-effective. PMID- 1908217 TI - [Study of the medial mamillary nucleus of the human hypothalamus in fresh cadavers]. AB - Morpho-functional state of the medial mamillary nucleus of the posterior hypothalamus in patients who had died from various diseases at the age of 18 to 80 years were studied by methods of quantitative histochemistry on the material of early necropsies. Nuclear changes were revealed depending on the age, type of main disease, character of thanatogenesis. The common and the earliest changes were those of microcirculatory bed resulting in the disturbance of interrelationships in the system neuron--neuropil--vessel. PMID- 1908218 TI - Sulphated glycosaminoglycan synthesis by developing rat submandibular gland secretory units. AB - This study examined the profile of S-GAGs synthesized by presecretory and secretory units isolated from rats at 17, 18 and 21 days in utero and 1, 6 and 35 days after birth. The units were incubated for 2 h in medium containing [35S] sodium sulphate and then processed and analysed. Secretory units from 17-day embryonic presecretory units produced a S-GAG profile composed of approx. 73% chondroitin sulphate and 26% heparan sulphate. When cells of the embryonic units undergo cytodifferentiation to become secretory cells (18 days in utero), there is a major change in the relative amounts of S-GAG synthesized with 54% of the S GAG produced being heparan sulphate and 41% chondroitin sulphate. There is a progressive increase in the relative amount of heparan sulphate produced and a concomitant decline in chondroitin sulphate as the secretory compartment of the gland matures. By 35 days after birth, the secretory units produced a S-GAG profile that was greater than 85% heparan sulphate and less than 10% chondroitin sulphate. The ratio of heparan sulphate/chondroitin sulphate production was 0.36 by 17-day embryonic presecretory units and shifted to 9.1 by 35-day postnatal units. PMID- 1908219 TI - Characterization of the solubilized glibenclamide receptor in a hamster pancreatic beta-cell line, HIT T15. AB - The glibenclamide receptor, a putative ATP-sensitive K+ channel in the hamster pancreatic beta-cell line HIT T15, was solubilized by using the zwitterionic detergent CHAPS. [3H]Glibenclamide binding was dependent on the incubation time and on the concentration of soluble membrane protein. Over 80% of [3H]glibenclamide bound could be displaced with 1 microM non-labelled glibenclamide. The curve relating specific binding to the concentration of [3H]glibenclamide (1-20 nM) showed saturation kinetics. Scatchard analysis suggested a single class of non-interacting binding sites with a Kd of 3.3 nM and a Bmax. of 90 fmol/mg of protein. [3H]Glibenclamide binding to solubilized membranes was inhibited by glibenclamide, tolbutamide and meglitinide. The relative potency of these agents on binding of [3H]glibenclamide to solubilized membranes was similar to that observed with microsomal preparations and paralleled their effects on K-ATP channel activity, measured as 86Rb efflux. These data show that the sulphonylurea receptor in the pancreatic beta-cell can be solubilized in an active form retaining specificity for sulphonylureas. ADP, which inhibits [3H]glibenclamide binding to microsomal preparations or intact HIT beta-cells, did not inhibit binding to the solubilized receptor. Incubation of intact HIT beta-cells with 125I-glibenclamide derivative followed by exposure to u.v. light resulted in covalent labelling of a peptide of 65 kDa on SDS/PAGE. The extent of labelling increased with 125I-glibenclamide derivative concentration (1 20 nM) and was inhibited in the presence of excess unlabelled glibenclamide. PMID- 1908220 TI - Active-site serine mutants of the Streptomyces albus G beta-lactamase. AB - By using site-directed mutagenesis, the active-site serine residue of the Streptomyces albus G beta-lactamase was substituted by alanine and cysteine. Both mutant enzymes were produced in Streptomyces lividans and purified to homogeneity. The cysteine beta-lactamase exhibited a substrate-specificity profile distinct from that of the wild-type enzyme, and its kcat./Km values at pH 7 were never higher than 0.1% of that of the serine enzyme. Unlike the wild-type enzyme, the activity of the mutant increased at acidic pH values. Surprisingly, the alanine mutant exhibited a weak but specific activity for benzylpenicillin and ampicillin. In addition, a very small production of wild-type enzyme, probably due to mistranslation, was detected, but that activity could be selectively eliminated. Both mutant enzymes were nearly as thermostable as the wild-type. PMID- 1908221 TI - Glutamine transport by basolateral plasma-membrane vesicles prepared from rabbit intestine. AB - L-Glutamine, a major energy substrate for intestinal epithelial cells, can be extracted from intraluminal contents across the brush-border membrane and from arterial blood via the basolateral membrane. The purpose of the present study was to characterize glutamine transport by the basolateral membrane of rabbit epithelial cells. Transport of glutamine by isolated basolateral-membrane vesicles was mediated by both Na(+)-dependent and Na(+)-independent carriers. Tests were performed to distinguish glutamine uptake by likely transport agencies, including Systems A, ASC, N, IMINO, NBB, L and asc. The Na(+)-dependent glutamine uptake was strongly inhibited by an excess of 2-(methylamino)isobutyric acid (MeAIB), and glutamine was equally effective in inhibiting MeAIB transport. The reciprocal inhibition analysis, as well as a sensitivity to increased H+ concentration, indicates that Na(+)-dependent glutamine transport across the basolateral membrane is mediated by System A. The saturable Na(+)-independent glutamine transport was markedly inhibited by 2-aminobicyclo-[2,2,1]-heptane-2 carboxylic acid ('BCH') and insensitive to changes in assay pH, suggesting uptake via System L rather than System asc. The presence of a Na(+)-dependent carrier to mediate active transport of glutamine across the basolateral membrane is probably essential to ensure a continuous supply of this vital substrate to the enterocyte in the post-absorptive state. PMID- 1908222 TI - Homodimer and heterodimer subunits of human prostate acid phosphatase. AB - Human prostatic acid phosphatase (PAP) isoenzymes, designated PAP-A and PAP-B, were isolated from human seminal plasma by sequential affinity chromatography on concanavalin A and L(+)-tartrate, a classic inhibitor of PAP. Both the major PAP A and the minor PAP-B isoenzymes exhibited a similar molecular mass (100 and 105 kDa respectively), multiple pI values (5.05-5.35 and 5.05-5.12), and substrate and inhibitor specificity. Immunological characterization revealed that PAP-B possesses distinct antigenic determinants, in addition to the common sites shared with PAP-A. SDS/PAGE indicated that both isoenzymes are composed of two subunits of 50 kDa each. At high salt concentration, PAP-B dissociated completely into single subunits of 50 kDa, whereas PAP-A remained intact at 100 kDa. PAP-B was resolved by reverse-phase h.p.l.c. into three components, designated alpha, beta and gamma, each of 50 kDa, at a molar ratio of approx. 2:1:1. PAP-A contained a single component of molecular mass 50 kDa. The single component of PAP-A and the alpha component of PAP-B possessed identical amino acid compositions and N terminal sequences, which were different from those of the beta and gamma components. These results indicate that human PAP contains three isoforms, alpha 2, alpha beta and alpha gamma. PAP-A, the major isoenzyme, is a homodimer consisting of two identical subunits (alpha 2), and PAP-B, the minor isoenzyme, is a mixture of two heterodimers, consisting of non-identical subunits (alpha beta and alpha gamma). PMID- 1908223 TI - The mechanism of tyrosinase-catalysed oxidative decarboxylation of alpha-(3,4 dihydroxyphenyl)-lactic acid. AB - Mushroom tyrosinase, which is known to catalyse the conversion of o-diphenols into o-benzoquinones, has been shown to catalyse the oxidative decarboxylation of 3,4-dihydroxymandelic acid [Sugumaran (1986) Biochemistry 25, 4489-4492]. To account for this unusual reaction, a quinone methide intermediate has been proposed. Since all attempts to trap this intermediate ended in vain, mechanistic studies were designed to support the formation of this transient product. Replacement of the alpha-proton in 3,4-dihydroxymandelic acid with a methyl group generates alpha-(3,4-dihydroxyphenyl)-lactic acid, the enzymic oxidation of which should produce 3,4-dihydroxyacetophenone as the end product if the oxidative decarboxylation proceeds through the quinone methide intermediate. Accordingly, chemically synthesized alpha-(3,4-dihydroxyphenyl)-lactic acid on enzymic oxidation produced 3,4-dihydroxyacetophenone as the major isolatable product. Non steady-state kinetic analysis of the enzyme reaction attested to the transient formation of the conventional quinone product. Thus the enzymic oxidation of alpha-(3,4-dihydroxyphenyl)-lactic acid seems to generate the conventional quinone, which, owing to its instability, is rapidly decarboxylated to yield the transient quinone methide. The coupled dieneonephenol re-arrangement and ketol enol tautomerism transforms the quinone methide into 3,4-dihydroxyacetophenone. PMID- 1908225 TI - A kinetic study of irreversible enzyme inhibition by an inhibitor that is rendered unstable by enzymic catalysis. The inhibition of polyphenol oxidase by L cysteine. AB - A kinetic study of the irreversible inhibition of an enzyme by an inhibitor that is depleted in the medium by its reaction with the product of enzymic analysis was made. The model is illustrated by the study of the inhibition of catecholase activity of polyphenol oxidase by L-cysteine. The inhibition is characterized by an initial lag period followed by a concomitant decrease in enzymic activity expressed when the steady state is reached, both kinetic parameters being modulated by enzyme, substrate and inhibitor concentrations. There is no analytical solution to the non-linear differential-equation system that describes the kinetics of the reaction, and so computer simulations of this dynamic behaviour are presented. The results obtained show that the system here studied presents kinetic co-operativity for a target enzyme that follows the simple Michaelis-Menten mechanism in its action on the substrate. PMID- 1908226 TI - Stoichiometric studies of beta-alanine transporters in rabbit proximal tubule. AB - The coupling ratio for the transport of beta-alanine and Na+, H+ and Cl- in luminal membrane vesicles isolated from proximal convoluted tubules (pars convoluta) and proximal straight tubules (pars recta) of rabbit kidney was examined. Indirect evidence indicates that 1 H+ and approx. 2 Na+, 1 Cl- (Na(+) dependent, high-affinity) or 1 Na+ (Na(+)-dependent, low-affinity) are co transported with beta-alanine in the pars convoluta. In pars recta, the two Na(+) dependent transporters exhibited the same stoichiometric properties respectively as in pars convoluta. PMID- 1908224 TI - Interactions of ricin with sinusoidal endothelial rat liver cells. Different involvement of two distinct carbohydrate-specific mechanisms in surface binding and internalization. AB - We have investigated the interactions of the plant toxin ricin with sinusoidal endothelial rat liver cells (EC). In these cells, ricin can be bound and internalized via either cell surface galactosyl residues or mannose receptors. Binding and uptake via galactosyl residues and mannose receptors was studied in the presence of mannan (1 mg/ml) and lactose (50 mM) respectively. Whereas most of the ricin binding was accounted for by cell surface galactosyl residues, uptake of ricin via mannose receptors was much more efficient than uptake via galactosyl residues. Internalized ricin is subject to extensive retroendocytosis (recycling to the cell surface from an early endocytic compartment). Retroendocytosis occurs after internalization of ricin via either pathway and to a much greater extent than for other glycoproteins taken up via mannose receptors of the EC. Hyperosmolarity (150 mM-sucrose), which is known to inhibit endocytosis from coated pits, strongly inhibited ricin uptake via mannose receptors, but had less effect on uptake via galactosyl residues. This suggests that only part of the galactose-specific uptake takes place from coated pits. Protein synthesis in EC was very sensitive to ricin [concn. causing half-maximal inhibition (IC50) = 1.3 x 10(-13) M]. Mannan was slightly more effective than lactose in protecting the EC protein synthesis from ricin toxicity. PMID- 1908228 TI - Drosophila chorion genes: cracking the eggshell's secrets. AB - The chorion genes of Drosophila are amplified in response to developmental signals in the follicle cells of the ovary prior to their transcription. Their expression is regulated both temporally and spatially within this tissue. They thus serve as models both for the regulation of DNA replication and of developmental transcription. The regulatory elements for DNA amplification have been delineated. Their analysis reveals that amplification is mediated by several regulatory regions and initiates at defined origins within the chorion cluster. Proteins involved in amplification are being identified both by mutations affecting amplification and by DNA binding studies. Regulatory elements for temporal as well as spatial control of chorion gene expression have been characterized, and two candidate transcription factor genes have been cloned. PMID- 1908227 TI - The human carbonic anhydrase I gene has two promoters with different tissue specificities. AB - Primer extension and S1 nuclease analysis of human carbonic anhydrase I (HCA1) mRNA transcripts in erythroid and non-erythroid tissues show that the HCA1 gene has two promoters with different tissue specificities, separated by 36 kb of DNA. The promoter of the HCA1 gene which is active in non-erythroid tissue shows strong sequence similarity with a similar region in the mouse CA1 gene, but has two equally used transcription start sites. PMID- 1908229 TI - Isolated hepatocytes are capable of excreting aflatoxin metabolites. AB - The intra- and extra-cellular concentrations of AFB1, AFM1, AFP1, AFQ1 and their conjugates were quantitatively determined after 60 min of incubation with [3H] AFB1 (1500 pmol/10(8) cells). Comparing the total concentrations of water-soluble conjugates, the eight fold greater amounts found in the medium (718 pmol) than in the cell (86 pmol) indicate that these detoxication products were excreted soon after they were formed. When the cells were perturbed with butylated hydroxyanisole (BHA), a noncompetitive inhibitor of the mixed-function oxidases, accumulations of intracellular AFB1 and extracellular AFB1 were observed. In a cell-free microsomal system, the AFB1 was metabolized at a slower rate than in intact cells. When the activation of AFB1 is blocked, the accumulation of intracellular AFB1 and decreased internalization of AFB1 suggest that AFB1 uptake, translocation of AFB1 from site of entry to site of actions, oxidation by cytochrome P-450-dependent monoxygenase, metabolic detoxication and conjugation reactions, and excretion of water soluble metabolites are linked. PMID- 1908230 TI - Selective inhibition of NADH-CoQ oxidoreductase (complex I) of rat brain mitochondria by arachidonic acid. AB - The effects of arachidonic acid on the enzyme complexes in the electron transport system were investigated using submitochondrial particles from rat brain. Arachidonic acid irreversibly inhibited NADH-CoQ oxidoreductase (complex I) activity, but had no effect on the activities of succinate-CoQ oxidoreductase (complex II), CoQH2-cytochrome c oxidoreductase (complex III), cytochrome c oxidase (complex IV), ATPase (complex V), glutamate dehydrogenase, and malate dehydrogenase up to 50 microM. The inhibition was dose-dependent with an IC50 value of 110 nmol/mg protein. The Lineweaver-Burk plot revealed that the inhibition by arachidonic acid was noncompetitive against CoQ with a Ki value of 33 microM and uncompetitive against NADH with a Ki value of 22 microM. PMID- 1908231 TI - The 717Val----Ile substitution in amyloid precursor protein is associated with familial Alzheimer's disease regardless of ethnic groups. AB - Alzheimer's disease (AD) is a devastating neurological disorder and the leading cause of dementia among aged individuals. The human amyloid beta protein, which is a cleavage product of amyloid precursor protein (APP), is a major component of the amyloid deposited in the brain of patients with AD. By using PCR direct sequencing of exon 17 (encoding part of the beta protein) of the APP gene, we have found that a Japanese AD patient harbours a C to T substitution, responsible for a valine to isoleucine change at position 717, heterogeneously. The mutation is exactly the same as that found in a Caucasian AD family by Goate et al. (1). Furthermore, the mutation was shown to co-segregate with AD in his family. These results suggest that the Val----Ile change in the APP causes AD, regardless of ethnic background. PMID- 1908232 TI - The plasminogen activator inhibitor-1 binding site in the kringle-2 domain of tissue-type plasminogen activator. AB - We have shown that synthetic peptides containing the amino acid sequence Asn-Arg Arg-Leu, derived from the amino acid sequence of the inner loop of the kringle-2 domain of tissue-type plasminogen activator (tPA), inhibited complex formation between two chain tPA and plasminogen activator inhibitor-1 (PAI-1) by binding to PAI-1. This binding was reversible and was inhibited by not only tPA but also by enzymatically inactive tPA. Quantitative analyses of the interaction of PAI-1 with the peptide containing the Asn-Arg-Arg-Leu sequence indicated that the PAI-1 binding site residues in the inner loop of the kringle-2 domain and is preferentially expressed in two chain tPA. PMID- 1908233 TI - Glycosylation sites identified by detection of glycosylated amino acids released from Edman degradation: the identification of Xaa-Pro-Xaa-Xaa as a motif for Thr O-glycosylation. AB - Here we report the use of automated Edman degradation of covalently linked glycopeptides to identify positively the sites of O- and N-glycosylation. The O glycosidic linkage of carbohydrate to the hydroxy amino acids Ser and Thr is a major form of post-translational modification. However, unlike Asn-linked glycosylation, which is identified by the consensus sequence Asn-Xaa-Thr/Ser, no simple motif conferring O-linkage to Thr and Ser has been described. After sequencing glycopeptides derived from two cell surface glycoproteins, a Thr-O glycosylation motif of Xaa-Pro-Xaa-Xaa, where at least one Xaa = Thr(Sac), has been defined. This motif predicts the site(s) of Pro- associated Thr-O glycosylation in O-glycosylated proteins, although it is clear that there are also other forms of Thr-O-glycosylation not associated with Pro. PMID- 1908234 TI - Biphasic rise caused by extracellular ATP in intracellular calcium concentration in bovine adrenocortical fasciculata cells. AB - We examined the effect of extracellular ATP on intracellular calcium concentration ([Ca2+]i) in bovine adrenocortical fasciculata cells. The suspended cells and the monolayer cells on coverslips were loaded with fura2. We found that ATP caused a rapid transient rise [Ca2+]i in dose-dependent manner in the presence of extracellular Ca2+ and that the rise in [Ca2+]i caused by ATP was biphasic. We did not observe the second phase in the absence of extracellular Ca2+. These results suggest that the first rise in [Ca2+]i caused by ATP is due to Ca2+ release from intracellular Ca2+ stores and subsequent rise due to Ca2+ influx across the plasma membrane. Furthermore, we found that the first phase of the monolayer cells consisted of two peaks. So it is possible that Ca2+ release from intracellular Ca2+ stores caused by ATP is induced by two different manners in adrenocortical fasciculata cells. In addition, monolayer cells are more useful than suspended ones in the examination of Ca2+ mobilization in adrenocortical fasciculata cells. PMID- 1908235 TI - Selective in vitro inhibition of human MOLT-4 T lymphoblasts by the novel purine nucleoside phosphorylase inhibitor, CI-972. AB - CI-972 (2,6-diamino-3,5-dihydro-7-(3-thienylmethyl)-4H-pyrrolo[3,2- d]pyrimidin-4 one monohydrochloride, monohydrate) is a competitive inhibitor of PNPase (E.C. 2.4.2.1., Ki = 0.83 microM) entering clinical trials as a T cell-selective immunosuppressive agent. Neither CI-972 (less than or equal to 50 microM) nor dGuo (less than or equal to 10 microM) inhibited [3H]Thd uptake by human MOLT-4 (T cell) or MGL-8 (B cell) lymphoblasts, but in the presence of 10 microM dGuo, the IC50 for CI-972 decreased to 3.0 microM for MOLT-4 but remained at greater than 50 microM for MGL-8. Inhibition of MOLT-4 growth was associated with an increase in dGTP that was dependent on CI-972 concentration and inhibited by 2' deoxycytidine. Growth could not be restored by hypoxanthine or adenine. No alterations in GTP pools were noted in MOLT-4, and neither GTP nor dGTP were altered in MGL-8. PMID- 1908236 TI - Characterization of mucin-type oligosaccharides with the sialyl-Le(a) structure from human colorectal adenocarcinoma cells. AB - Oligosaccharides with the sialyl-Le(a) structure have been isolated on an affinity column of a monoclonal antibody, MSW 113, from mucin-type glycoproteins derived from the surfaces of SW 1116 and LS 180 cells, and their secretions. The oligosaccharides were polydisperse with respect to molecular size, the oligosaccharides derived from glycoproteins in culture media being larger than those in cell lysates, as assessed by gel filtration. Some of the oligosaccharides were susceptible to degradation by endo-beta-galactosidase (E. freundii), as judged from the change in the gel filtration pattern. These results indicate that oligosaccharides with the sialyl-Le(a) structure derived from mucin type glycoproteins produced by human colonic cancer cells are extremely large in size and complex in structure, and that some of them contain the poly-N acetyllactosamine structure. PMID- 1908237 TI - 17R(18S)epoxyeicosatetraenoic acid, a cytochrome P-450 metabolite of 20:5n-3 in monkey seminal vesicles, is metabolized to novel prostaglandins. AB - Eicosapentaenoic acid (20:5n-3) is metabolized by cytochrome P-450w3 of monkey seminal vesicles to 17R(18S)epoxy-5,8,11,14-eicosatetraenoic acid (17R(18S)EpETE). PGH synthase is abundant in this tissue. Racemic 17(18)EpETE was therefore investigated as a substrate of PGH synthase. The main products were identified as two diastereoisomers of 17(18)epoxyprostaglandin E2, which were formed in a 4:5 ratio. The structures were confirmed by authentic material. The natural epoxide enantiomer can thus be metabolized to novel 17R(18S)epoxyprostaglandins. PMID- 1908238 TI - Structural and immunological evidence for the identity of prolyl aminopeptidase with leucyl aminopeptidase. AB - Prolyl aminopeptidase (EC 3.4.11.5) has been assumed to be a unique enzyme catalyzing specifically the removal of unsubstituted NH2-terminal L-prolyl residues from various peptides and to be distinct from leucyl aminopeptidase (EC 3.4.11.1). In the present study, prolyl aminopeptidases were purified to apparent homogeneity from pig small intestine mucosa and human liver and their NH2 terminal amino acid sequences were determined together with that of pig kidney leucyl aminopeptidase. The NH2-terminal 24-residue sequence of pig intestinal prolyl aminopeptidase was shown to be identical with that of pig kidney leucyl aminopeptidase. The NH2-terminal sequence of human liver prolyl aminopeptidase was also shown to be very similar to that of pig kidney leucyl aminopeptidase. Further, pig intestinal prolyl aminopeptidase and pig kidney leucyl aminopeptidase were immunologically indistinguishable. These lines of evidence strongly suggest that prolyl aminopeptidase is identical with leucyl aminopeptidase. PMID- 1908239 TI - Modulation of gene expression by high and low density lipoproteins in human vascular smooth muscle cells. AB - Low density lipoprotein and its oxidized form has been implicated in the process of arteriosclerosis which involves growth-related events in the smooth muscle cells of the arterial wall. The induction of so-called early-growth response genes e.g. c-myc and c-fos can serve as an indicator for these growth-related events. In cultured human vascular smooth muscle cells, both LDL and HDL3 were individually capable of stimulating c-myc and c-fos expression in a concentration dependent manner. However, when they were used in combination, depending on the proportion of HDL3 to LDL, c-fos but not c-myc expression was less pronounced than with the single components. In contrast to HDL3 and LDL alone, a combination of the two lipoproteins also blunted both the expression of autoinduced transforming growth factor beta transcripts and the transforming growth factor beta-induced increase of c-fos mRNA. It is concluded that a) the inhibition of transforming growth factor beta autostimulation by HDL3 plus LDL may involve reduced AP-1 activity via a reduction of c-fos expression by the lipoprotein combination and b) the ratio HDL3:LDL might influence the pathogenesis of arteriosclerosis via growth-related events in the arterial wall. PMID- 1908240 TI - L-arginine stimulates an endogenous ADP-ribosyltransferase. AB - An ubiquitous biochemical pathway known to synthesize nitric oxide (NO) from L arginine has been identified in many cell types. Recent studies indicate that besides activating soluble guanylate cyclase NO is likely to have effects unrelated to the known signal transduction pathway. Activation of the soluble NO synthase stimulates an endogenous ADP-ribosylation of a predominant 39 kDa protein, known to be activated by NO releasing agents. This is demonstrated using the cytosolic fraction of rat cerebellum and HL-60 cells. The ADP-ribosylation is suppressed by the known NO synthase inhibitors N-nitro-L-arginine and N-methyl-L arginine. These observations indicate that NO derived from its physiological precursor L-arginine activates an endogenous ADP-ribosyltransferase. PMID- 1908241 TI - Transforming growth factor-beta modulates eicosanoid metabolism in osteogenic osteosarcoma cells. AB - The metabolites of cycloxyegenase and lipoxygenase pathways are known to play an important role in the bone metabolism involving osteoclast and osteoblast interaction, bone resorption and morphogenesis. The recently discovered growth factor TGF-beta is abundant in bone and some of its intracellular and extracellular effects depend on de novo synthesis of eicosanoids. However, the effect of TGF-beta on the synthesis and the release of eicosanoid by bone cells is essentially unknown. In the present study we have identified the main eicosanoid metabolites produced by osteogenic osteosarcoma cell-line SAOS1 and investigated how production and release of these is affected by TGF-beta. We found that the leukotriene C4 is the main metabolite produced by these cells and that TGF-beta induces concentration-dependent, quantitative and qualitative alterations in eicosanoid production and release by human osteogenic osteosarcoma cells SAOS1. PMID- 1908242 TI - Arachidonate supports hydrolysis of phosphatidylinositol by neutrophil cytosolic phospholipase C: relation to NADPH oxidase. AB - NADPH oxidase is a superoxide-generating, membrane-bound complex activated in stimulated phagocytes or in a reconstituted system consisting of membranes, cytosolic components and arachidonate or SDS. To delineate mechanism of oxidase activation in the cell-free system, hydrolysis of phosphoinositides in the combined membrane-cytosol oxidase mixture was investigated. Arachidonate promoted hydrolysis of membrane-[3H]-phosphatidylinositol by cytosolic phospholipase C. PI hydrolysis was similarly supported by other unsaturated fatty acids and by SDS. Unlike activation of the NADPH oxidase, PI hydrolysis required the presence of calcium ions. Implications of these findings to the mechanism of NADPH oxidase activation are discussed. PMID- 1908243 TI - Changes in carbonic anhydrase may be the initial step of altered metabolism in hypertension. AB - Carbonic anhydrase (CA) is a well characterized pH regulatory enzyme in most of the tissues in the body. Changes in activities of CA have been associated with altered metabolism, especially in diabetes mellitus. Insulin resistance and hyperinsulinemia are common in hypertension. To investigate the possible role of CA, we measured the CA activity spectrophotometrically using p-nitrophenyl acetate as a substrate and acetazolamide, the specific inhibitor, in erythrocytes from normotensive and essential hypertensive subjects. Further, to evaluate the insulin action on CA, we used two different hemolysates; (i) insulin applied into hemolysate and (ii) hemolysate from insulin treated erythrocytes in vitro before the determination of CA activity. Two different levels of CA activities were obtained in these patients. CA activities were much lower (mean +/- SD, 0.88 +/- 0.19 U/min/mL) and higher (mean +/- SD, 1.77 +/- 0.23 U/min/mL) in patients than the normotensive controls (mean +/- 1 SD, 1.41 +/- 0.1 U/min/mL). These differences in both the groups were statistically significant (p less than 0.001). Similarly, total esterase activities in patients were (1.41 +/- 0.27 U/min/mL) that was 30% less in low activity group and (2.47 +/- 0.25 U/min/mL) that was 22% more in higher activity group in comparison with those from normotensives (2.02 +/- 0.17 U/min/mL). The relative percent of CA activities of insulin treated erythrocytes from normotensives and hypertensives were 11% and 18% higher than without insulin (p less than 0.05). No difference was observed when insulin was applied in the hemolysate. We conclude that essential hypertensive patients are associated with altered CA activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1908244 TI - The effect of estramustine derivatives on microtubule assembly in vitro depends on the charge of the substituent. AB - Estramustine, and derivatives of estramustine with a charged substituent at position 17 on the estrogen moiety, have been investigated for their effects on bovine brain microtubules in vitro. The negatively charged estramustine phosphate has been found previously to be a microtubule-associated protein (MAP)-dependent microtubule inhibitor [Wallin M, Deinum J and Friden B, FEBS Lett 179: 289-293, 1985]. In the present study the binding of estramustine phosphate to MAP2 and tau was investigated. Both these MAPs were found to have two to three binding sites for estramustine phosphate which is compatible with the reported number of basic amino acid repeats of these MAPs, considered to be the ultimate tubulin binding domains. The Kd for the binding of estramustine phosphate to MAP2 was estimated to be 20 microM at 4 degrees, and for the binding of tau, 200 microM. The rate of dissociation was very low (T1/2 greater than 2 hr), which indicates that the binding of estramustine phosphate may stabilize the protein-drug complex by changing the protein conformation. Two new negatively charged estramustine derivatives, estramustine sulphate and estramustine glucuronide, were found to be similar MAP-dependent microtubule inhibitors. The concentration for 50% inhibition of assembly was 100 microM for the sulphate derivative, the same as found previously for estramustine phosphate, and 250 microM for the more bulky estramustine glucuronide. A positively charged derivative, estramustine sarcosinate, did not inhibit microtubule assembly or alter the composition of the coassembled MAPs. The morphology of the microtubules was, however, affected. The uncharged estramustine bound to both tubulin and MAPs, but no effects were seen on microtubule assembly, the composition of coassembled MAPs or the microtubule morphology. Our results suggest that only negatively charged estramustine derivatives have a MAP-dependent microtubule inhibitory effect. The two new negatively charged derivatives could therefore be valuable tools in the study of tubulin-MAP interactions. The results also confirm that these interactions between tubulin and MAPs are mainly electrostatic. PMID- 1908245 TI - The role of Ha-ras oncogenes in growth factor independence in rat mammary carcinoma cells. AB - To determine if activation of the c-Ha-ras-1 gene is involved in the acquisition of growth factor independence in 7,12-dimethylbenz[a]anthracene (DMBA)--and N nitrosomethylurea (NMU)--induced rat mammary carcinomas, three strategies were used. First, Ha-ras DNA from growth factor-independent DMBA-induced rat mammary tumor cells was amplified using the polymerase chain reaction and examined for the presence of mutations in the first and second exons of Ha-ras-1 by restriction fragment length polymorphism analysis, allele-specific oligonucleotide hybridization, and direct sequencing. No mutations were found in the codon 12/13 or codon 61 regions of the Ha-ras-1 gene. Second, a similar analysis of an NMU-induced mammary carcinoma showed that it harbored an activating mutation in codon 12 of Ha-ras-1. When analyzed for growth factor requirements, these cells were found to express limited growth potential in all media tested, in contrast to growth factor-independent cells, which proliferated extensively in the presence or absence of exogenous growth factors. Third, growth factor-dependent rat mammary tumor cells and spontaneously immortalized rat normal mammary epithelial cells were transfected with an activated form of the Ha ras-1 (T24) gene, and the growth factor requirements of the transfected cells were examined. The ras-transfected cells retained the growth factor requirements of the normal cells. In addition, ras-transfected cells were transplanted into syngeneic rats and nude mice, and no tumors developed after 6 mo in vivo. These results indicate that, in rat mammary tumor cells, neither growth factor independence in vitro nor transplantability are directly mediated by Ha-ras oncogenes. The results also suggest that ras activation and growth factor independence may be associated with independent pathways to malignancy in rat mammary tumorigenesis. PMID- 1908246 TI - The use of rabbit polyclonal antibodies for the isolation of carcinogen-adducted DNA by immunoprecipitation. AB - Polyclonal rabbit antibodies elicited against DNA with high levels of (+/-) 7r,8t dihydroxy-9t,10t-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE-I) adducts were used to isolate DNA fragments modified by this carcinogen. DNA treated in vitro with different concentrations of BPDE-I was used as substrate in double-antibody immunoprecipitation reactions. The IgG fraction from immune rabbit serum (primary antibody) was reacted with single-stranded plasmid DNA bearing BPDE-I adducts, and the complexes were immunoprecipitated using goat antirabbit-IgG as secondary antibody. DNA was isolated from the immunoprecipitated pellet, blotted onto nitrocellulose or nylon, and hybridized with 32P-labeled sequences homologous to a fragment of the plasmid DNA used in the assay. The recovery of both DNA and adducts in the immunoprecipitated pellet increased with the level of carcinogen adduction of the DNA. The immunoprecipitation reaction appeared to be more efficient for fragments of DNA containing a high number of adducts. The amount of 32P-hybridizing material recovered by immunoprecipitation was virtually identical to the amount added to the reaction in DNA samples that contained three adducts per 10(3) nucleotides. PMID- 1908247 TI - The cost of treating pressure ulcers in a long-term care facility. AB - Although there is rising concern with the cost of pressure ulcer treatment, actual expenditures have not been quantified in many settings. A retrospective research design was used to describe the costs incurred by an 830-bed long-term care facility to treat 240 pressure ulcers over a five-year period. The total cost was $116,416 for the study period. The mean cost of treatment was $5.35/pressure ulcer/day. These costs are substantially lower than the costs of pressure ulcer treatment in acute care. Further study to compare treatment costs with prevention costs would provide useful information on the cost benefits of prevention. PMID- 1908248 TI - A probable defect in the beta-oxidation of lipids in rats fed alcohol for 6 months. AB - Studies on fatty acid oxidation were made in rats fed for 6 months on a liquid diet containing 15% total calories as ethanol. After 6 months, a marked diminution was observed in the in vivo production of 14CO2 from labeled palmitate and octanoate in the ethanol-fed animals compared to their pair-fed isocaloric controls not receiving alcohol. Similar results were obtained in 14CO2 formation from 14C-fatty acids using liver mitochondria from these ethanol-fed rats after 6 months. The effect on octanoate beta-oxidation was larger than that for palmitate. Addition of purified acyl CoA dehydrogenase complexes and additional electron transfer flavoprotein complex to the mitochondria suggested that the ethanol-fed animals could have been deficient in the medium-chain acyl CoA dehydrogenase complex. PMID- 1908249 TI - Drinking of high concentrations of ethanol versus palatable fluids in alcohol preferring (P) rats: valid animal model of alcoholism. AB - A genetically based animal model of alcoholism has been characterized in Wistar derived rats in terms of their preference (P rats) or lack of preference (NP rats) for 10% ethanol over water. The present experiments were designed to determine: 1) whether a 10% solution of ethanol is the optimal concentration for differentiation of these lines; 2) what concentrations of ethanol are maximally preferred by P and NP rats; and 3) whether highly palatable fluids presented simultaneously with each rat's preferred solution of ethanol would alter the patterns of drinking by either the P or NP or both lines of rats. A three-bottle procedure was used to establish preference for ethanol in the presence of water as well as highly palatable solutions. The results showed that, when concentrations ranging from 3-30% were presented over a 12-day test interval, the mean absolute intake of ethanol of the P rats was 6.7 g/kg per day, with a maximum intake of 10.9 g/kg per day at the 25% concentration. These levels of intake were significantly higher than the 4.3 g/kg per day consumed during the presentation of the commonly used constant concentration of 10%. Similarly, the mean absolute intake of ethanol by the NP rats was also elevated significantly at concentrations of 15-30% (2.0 g/kg per day) above that consumed at the 10% concentration (0.4 g/kg).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1908250 TI - The formation of a paracrystalline structure from muscle F-actin and oligolysine. AB - At very low ionic strength (gamma less than 0.05) oligohomopolymers of lysine cause lateral association of muscle F-actin filaments into ordered structures which appear at low magnification in electron-micrographs as rigid needles. At higher magnification these aggregates display regular quasicrystalline patterns. The structures dissolve reversibly when the ionic strength is raised suggesting that F-actin filaments are crosslinked by oligolysine due to electrostatic forces. PMID- 1908251 TI - The corticospinal tract attains a normal configuration in the absence of myelin: observations in jimpy mutant mice. AB - The corticospinal projection was examined in dysmyelinated, jimpy mice and in unaffected littermates following cortical injections of either wheat germ agglutinin conjugated to horseradish peroxidase or biocytin. Corticospinal axons in both phenotypes traverse the medulla within a well-defined pyramidal tract, decussate within several fascicles at the spinomedullary junction, and extend down the spinal cord in a compact bundle in the ventral-most part of the dorsal funiculus. Very few labeled fibers are seen separated from the main bundle. This normal configuration of the corticospinal tract is attained despite the virtual absence of CNS myelin in jimpy mice. It seems unlikely then that the myelin normally present in fiber bundles adjacent to this relatively late emerging projection can significantly influence pathway selection during its development. PMID- 1908253 TI - Synaptophysin is sorted from endocytotic markers in neuroendocrine PC12 cells but not transfected fibroblasts. AB - The targeting of synaptophysin, a major synaptic vesicle protein, in transfected nonneuronal cells has important implications for synaptic vesicle biogenesis, but has proved controversial. We have analyzed four transfected cell types by differential centrifugation and velocity gradient sedimentation to determine whether synaptophysin is targeted to endosomes or to synaptic vesicle-like structures. Synaptophysin was recovered only in vesicles that sedimented more rapidly than synaptic vesicles. The synaptophysin-containing vesicles were labeled if a surface-labeled cell was warmed to 37 degrees C, comigrated with transferrin receptor-containing vesicles on velocity and density gradients, and could be completely immunoadsorbed by anti-LDL receptor tail antibodies. These data demonstrate that synaptophysin was targeted to the early endocytotic pathway in the transfected cells and are inconsistent with the suggestion that synaptophysin expression induces a novel population of vesicles. Targeting of synaptophysin to early endosomes implicates their role in synaptic vesicle biogenesis. PMID- 1908252 TI - The A5 antigen, a candidate for the neuronal recognition molecule, has homologies to complement components and coagulation factors. AB - The A5 antigen is a neuronal cell surface protein of Xenopus presumed to be involved in the neuronal recognition between the optic nerve fibers and the visual centers. Analyses of cDNA clones revealed that the A5 antigen is a class I membrane protein containing two different internal repeats in the extracellular segment. The first repeat bears homology to domain III of complement components C1r and C1s, and the second repeat is homologous to the C1 and C2 domains of coagulation factors V and VIII. The mRNA for the A5 antigen was present in retinal ganglion cells and visual center neurons. Nonneuronal cells in the peripheral and central nervous systems did not express the mRNA for the A5 antigen. PMID- 1908254 TI - Aldehyde tanning: the villain in bioprosthetic calcification. AB - Preservation of bioprosthetic valves may play a role in valvular calcification. Subcutaneous implants in rats were used to test the effect of different preservation solutions. Fifty male Sprague-Dawley rats were divided into five groups. Fresh bovine pericardium was treated in one of five ways: group A: 99.5% glycerol for 1 week; group B: as group A, then normal saline wash and 0.25% formaldehyde storage for 24 h; group C: as group A, then normal saline wash and 4% formaldehyde storage for 24 h; group D: as group A, then normal saline wash and 0.625% glutaraldehyde storage for 24 h; group E: 0.625% glutaraldehyde and 4% buffered formaldehyde storage. Treated bovine pericardium was cut into 1-cm2 pieces and washed for 30 min with normal saline before implantation. In each animal, three pieces were implanted in the subcutaneous tissue of the back. After 70 days, retrieved specimens were examined grossly, and X-ray densitometry, calcium analysis, and histological examinations were carried out. The results showed that glycerol-treated tissue (group A) had less calcification (calcium 6.92 +/- 4.46 micrograms/mg dry weight) than other groups: group B (calcium 323.12 + 63.56 micrograms/mg dry weight); group C (calcium 240.65 + 13.47 micrograms/mg dry weight); group D (calcium 232.29 + 13.01 micrograms/mg dry weight). These differences were markedly significant (p less than 0.0001). It appears that aldehydes play an important role in the calcification of bioprosthetic valves. Experience with glutaraldehyde- and glycerol-treated pericardium in valvular applications in sheep support these observations. PMID- 1908256 TI - [Therapeutic trial in a family with late cerebellar atrophy]. PMID- 1908255 TI - [Complex I (NADH coenzyme-Q-reductase) deficiency, MELAS syndrome and hypertrophic cardiomyopathy]. AB - A 24-year-old male had a deficiency of the complex I (NADH coenzyme-Q-reductase) of the mitochondrial respiratory chain, which clinically presented as a mitochondrial encephalomyopathy, with lactic acidosis and stroke-like episodes (MELAS syndrome). The encephalopathic episodes were preceded by migraine and were characterized by focal deficit signs, motor partial seizures and hypodense areas in the CT scan. An echocardiographic diagnosis of hypertrophic cardiomyopathy without intracavitary thrombi was made. It is suggested that hypertrophic cardiomyopathy is caused by the mitochondrial abnormalities that have been reported in the myocardium, and that migraine and cerebral infarctions are associated with abnormalities in the mitochondria from the endothelium and smooth muscle fibres of the cerebral small arteries and arterioles. PMID- 1908257 TI - [Application of ambulatory cassette EEG system to the polysomnography in childhood epilepsy]. AB - Using an ambulatory cassette EEG system (Oxford Medilog 9000), polysomnography was performed in 25 cases of children with epilepsy and 25 normal children. The results revealed decreases in REM sleep and REM density in intractable epilepsy. An increase of slow waves was observed during REM sleep in severe myoclonic epilepsy in infancy or its adjacent group, and this result was more clearly demonstrated by an EEG auto analysis with fast Fourier transform. This above ambulatory cassette EEG system will be utilized more easily for polysomnography, and contribute to the research not only of the pathophysiology of epilepsy but also of the sleep mechanism itself. PMID- 1908258 TI - [A case of facioscapulohumeral muscular dystrophy with infantile spasms, sensorineural deafness and retinal vessel abnormality]. AB - We report an 18-year-old female with facioscapulohumeral dystrophy (FSHD), who had sensorineural deafness, retinal vessel abnormality, mental retardation, and epilepsy. She had infantile spasms at 6 months of age. Muscle atrophy and weakness of facial muscles were first noticed at 3 years of age. From 10 years of age, she had rapidly progressive generalized muscle weakness especially of facial, neck and truncal muscles with marked lordosis. Although mental retardation is commonly complicated with FSHD, infantile spasms or epilepsy has never been reported. Not only mental retardation but epilepsy may be one of the central nervous system symptoms in a systemic disorder, FSHD. PMID- 1908259 TI - [Cerebral blood flow changes in a patient recovered from hypocarbia]. AB - The changes of cerebral blood flow velocity (CBFV) and pulsatility index (PI) in anterior cerebral artery were examined by cranial color Doppler ultrasonography while a patient recovered from hypocarbia. As arterial PCO2 was elevated, PI was decreased and color imaging of CBF from basilar artery to anterior cerebral artery were improved in sagittal view. Hypocarbia is considered to induce the constriction of the cerebral vessels and the decrease of CBF in premature infants. PMID- 1908260 TI - [Exacerbation of partial seizures in a case with heterotopic gray matter using antiepileptic drugs]. AB - A two-year-old, right-handed girl was admitted to our hospital with a history of partial seizures. The first seizure, conjugated eye movements and head turning to the right, occurred at the age of 24 months. Later, she suffered from several seizures daily at the age of 34 months. At the age of 35 months, she was admitted to our hospital. On admission her neurological examination was normal. EEG showed a left parietal spike focus. A computed tomographic scan showed a small hyperdense area in the left parietal lobe without contrast enhancement. She was treated with carbamazepine (CBZ : 6 mg/kg/day). When seizures occurred several times within an hour, intravenous or rectal administration of diazepam (DZP : 0.3 mg/kg/dose) was added. However, she complained of sleepiness. The seizures occurred more frequently than before, 50 to 80 times daily, and became secondarily generalized. We thought that the exacerbation of the seizures resulted from the somnolence caused by DZP and CBZ. Consequently, these drugs were discontinued, and phenytoin was begun. She has since been free of seizures for two years. Approximately one year after the discontinuance of DZP and CBZ, heterotopic gray matter and abnormal gyri involving the left parieto-temporal lobe were found by magnetic resonance imaging (MRI). MRI is useful for detecting small heterotopic gray matter. To summarize this case, one should consider the possibility that excessive polytherapy induces seizures, particularly in patients with structural brain abnormalities such as heterotopic gray matter. PMID- 1908261 TI - Horizontal-cell gap junction in the goldfish retina: area and density of particles as revealed by complementary freeze replicas. AB - Aiming at a morphological evaluation of horizontal cell gap junctions under intraocularly injected dopamine and 6-OH-dopamine influences as compared with those in the light and dark periods, the percentage of the junctional areas was computed by planimetry, and the distribution density of connexon particles by visual counting, on complementary freeze-replica electron micrographs. The outer plexiform layer was tentatively divided into the external-horizontal-somatic, intermediate-mixed-fibrous and internal-axon-terminal sublayers. The total number of connexon particles per cell seemed relatively unchanged, because the density of the particles was lower in the light period and after the dopamine treatment than in the dark and after the 6-OH-dopamine treatment; the percentage of the junctional area was conversely greater in the former than in the latter. The mode of response of the gap junction was presumed to occur in parallel with each of the sublayers after the chemical interference. PMID- 1908262 TI - A method for the demonstration of NADPH-diaphorase activity in anuran species using unfixed retinal wholemounts. AB - The presence of NADPH-diaphorase enzyme has been previously revealed in fixed mammalian retinal tissue (Sagar, 1986). Fixed retinae of Bufo marinus and Xenopus laevis failed to yield selective staining when reacted for NADPH-diaphorase. Satisfactory staining of retinal neurons was attained when the histochemical reaction was carried out in unfixed retinal wholemounts. The applied method included the following steps: 1) Dissection of the fresh retina and the separation of the neural retina from all other coats of the eye ball, including the vitreal tissue; 2) pretreatment with 300 mM sucrose in phosphate buffer; 3) incubation with NADP, malic acid and nitroblue tetrazolium in phosphate buffer (pH 7.6); and 4) fixation of the tissue in 10% buffered formaldehyde overnight followed by whole mounting. For control, fixed and unfixed rabbit and human retinae were also reacted for NADPH-diaphorase according to the above method. In these species specific staining was achieved only with fixed tissues. The possible implications of revealing NADPH-diaphorase enzyme activity in fixed mammalian and non-fixed anuran tissues are discussed. PMID- 1908263 TI - NADPH-diaphorase positive neurons in the retina of Bufo marinus: selective staining of bipolar and amacrine cells. AB - Unfixed retinal tissues of adult Bufo marinus were reacted for NADPH-diaphorase histochemistry that resulted in selective staining of populations of bipolar and amacrine cells. The number of stained bipolar cells in the retina was estimated to be 233,600 +/- 38,900 (mean +/- S.D.). These cells were non-uniformly distributed across the retina with the highest density of 4,308 cells/mm2 along the visual streak decreasing to lowest density of 1,378 cells/mm2 at the dorsal and ventral poles of the retina. The stained bipolar cells represented a morphologically uniform population. The number of labelled amacrine cells in the retina amounted to 3,116 +/- 405 including 251 cells that were displaced into the ganglion cell layer. Labelled amacrine cells were also unevenly distributed; with no stained cells in the retinal centre from where the density increased steadily to 72 cells mm2 in the retinal periphery. NADPH-diaphorase positive amacrine cells were classified on the basis of their dendritic arborization pattern into three morphological types: 1) narrow-field cells both at the periphery and the centre of the retina; 2) wide-field amacrine cells, and 3) amacrines with eccentric medium-sized dendritic field. The results of this study provide evidence for the presence of NADPH-diaphorase containing neurons in the anuran retina. Furthermore, this is the first report on the selective staining of bipolar cells for NADPH-diaphorase in the vertebrate retina. PMID- 1908264 TI - Immunocytochemical localization of synaptophysin (protein p38) and synapsin I in nerve terminals of rat neurohypophysis. AB - Synaptophysin and synapsin I, the synaptic vesicle-associated proteins, were demonstrated immunocytochemically in nerve terminals of the neurohypophysis of rats. Although both are associated with microvesicles 50-60 nm in diameter, they are not localized on or around the large neurosecretory granules nor the clear vacuoles, 100-200 nm in diameter. These findings strongly suggest that the microvesicles in the nerve terminal of the neurohypophysis are, for the most part, not the structures involved in the retrieval of the limiting membranes of the released neurosecretory granules, but rather typical synaptic vesicles. The clear vacuoles, which are negative for synaptophysin and synapsin I, are considered to be related to the retrieval of the limiting membranes of the released neurosecretory granules. PMID- 1908265 TI - Nutrition and the use of metabolic assessment in the ventilator-dependent patient. AB - Nutritional support is an important aspect of care in hospitalized patients, especially those receiving mechanical ventilation. While nutritional assessments can help guide the clinician in determining appropriate caloric intake requirements and refeeding schedules, few tools exist to evaluate the consequences of over- or underfeeding. Metabolic assessment using indirect calorimetry is a new method of nutritional assessment for use at the bedside of the weaning patient. The data obtained from a metabolic assessment can be used to adjust formulas and total caloric intake as well as differentiate between dead space and elevated carbon dioxide production as reasons for persistent hypercarbia. PMID- 1908266 TI - [Feeding jejunostomy using a G.I.A]. PMID- 1908267 TI - Pensions for nurses. PMID- 1908268 TI - Romania: fingers through the bars of a cot. PMID- 1908270 TI - UKCC: behind the scenes. PMID- 1908269 TI - Social benefits: sorting out rules and benefits. PMID- 1908271 TI - Asthma education and prophylaxis. PMID- 1908272 TI - Management of viral hepatitis. PMID- 1908273 TI - Health education in psychiatry. Part 1. PMID- 1908274 TI - Computers as an aid in nurse education. PMID- 1908275 TI - Opportunity afforded by junior doctors' hours being reduced. PMID- 1908276 TI - Mental health: needles and CPNs. PMID- 1908277 TI - Cardiology update. The moon's a balloon. PMID- 1908278 TI - Cardiology update. Coronary angioplasty. PMID- 1908279 TI - Cardiology update. Development of balloon angioplasty. PMID- 1908280 TI - Cardiology update. The cutting edge. PMID- 1908281 TI - Cardiology update. Restenosis after coronary angioplasty. PMID- 1908282 TI - Cardiology update. A new synthetic blood product. PMID- 1908283 TI - Cardiology update. Endovascular stents. PMID- 1908284 TI - Virginia Bottomley: a woman's place is in the 'House'. Interview by Norah Casey. PMID- 1908285 TI - 'Wipers or bust'. PMID- 1908286 TI - Focus on East Anglia. Sense of adventure. Interview by Linda Thomas. PMID- 1908287 TI - Advances in hormone replacement therapy. PMID- 1908288 TI - The advanced nurse practitioner. Part 1. PMID- 1908289 TI - Health education in psychiatry. Part 2. PMID- 1908290 TI - Starving night nurses. PMID- 1908291 TI - Cancer nursing. Grasping the opportunities. PMID- 1908292 TI - Cancer nursing. A society for all nurses. PMID- 1908293 TI - Cancer nursing. Video teaching aid for European nurses. PMID- 1908295 TI - Cancer nursing. Standards in cancer care. PMID- 1908294 TI - Cancer nursing. Communicating with cancer patients. PMID- 1908296 TI - HIV testing: to test or not to test. PMID- 1908297 TI - A critical view of nursing: a caring profession? PMID- 1908298 TI - The Clay column. Paradise lost. PMID- 1908299 TI - Paediatric bone marrow transplants. PMID- 1908300 TI - Helping to ease pain therapeutically. PMID- 1908302 TI - Acquiring minimal counselling skills. PMID- 1908301 TI - Future trends in infection control. PMID- 1908303 TI - Coming of age. PMID- 1908304 TI - Staff retention: learning the wrong lesson. PMID- 1908306 TI - Orthopaedic nursing. Preparing for advanced practice. PMID- 1908305 TI - Lateral nursing: Renaissance general nurse. PMID- 1908307 TI - Orthopaedic nursing. The Society newsletter. PMID- 1908308 TI - Orthopaedic nursing. United we stand. PMID- 1908309 TI - High-dose cytostatic agents in allogeneic bone marrow transplantation: comparison of the engraftment promoting potential. AB - We investigated the potential of various cytostatic agents for preventing graft rejection following allogeneic bone marrow transplantation. LEW rats received a lethal dose (35 mg/kg) of busulfan followed by injection of 1 x 10(8) F1(CAP x LEW) marrow cells, which are unable to induce a graft-versus-host reaction in LEW recipients. Rejection of the marrow graft was assessed by monitoring haematocrit and granulocyte counts. Due to its weak immunosuppressive activity, busulfan by itself is unable to allow engraftment of allogeneic marrow. Therefore, agents administered in addition to busulfan can be tested for their capacity to prevent marrow graft rejection. 120 mg/kg of cyclophosphamide, 20 mg/kg of ACNU and 240 mg/kg of ifosfamide completely prevented rejection of the allogeneic marrow. Maximum doses of BCNU applicable in conjunction with busulfan reduced the rejection rate to 12% (30 mg/kg) and 17% (40 mg/kg), whereas the antitumour agents thiotepa, melphalan, and carboplatin exhibited a very limited engraftment promoting potential in this experimental setting. Thus, BCNU (carmustine), ACNU (nimustine), and ifosfamide might be suitable candidates for conditioning of allogeneic bone marrow graft recipients. PMID- 1908310 TI - Activation of class I HLA expression by TNF-alpha and gamma-interferon is mediated through protein kinase C-dependent pathway in CML cell lines. AB - The combination of tumour necrosis factor alpha (TNF alpha) and gamma-interferon induced transcription of class I HLA genes in chronic myelogenous leukaemia (CML) cell lines through the formation of a complex between nuclear proteins and the transcriptional enhancers associated with these genes. Although gamma-interferon or TNF-alpha stimulated expression of class I HLA antigens in the EM2 and K562 CML cell lines when used alone, the effect of the combination of TNF-alpha and gamma-interferon was greater than that observed with either agent alone. The induction of class I HLA expression by gamma-interferon and TNF-alpha was inhibited completely by the isoquinoline sulfonamide H7, an inhibitor of protein kinase C. We conclude that the enhancement of the gamma-interferon induced transcriptional activation of class I HLA gene expression by TNF-alpha involves a protein kinase C-dependent pathway. PMID- 1908312 TI - Refractory chronic pure red cell aplasia (PRCA) treated with vincristine and daunorubicin. PMID- 1908313 TI - Immunoprophylaxis for rhesus disease--expensive but worth it? PMID- 1908311 TI - T cell-mediated inhibition of erythropoiesis in aplastic anaemia: the possible role of IFN-gamma and TNF-alpha. AB - The inhibitory activity of T cells on autologous erythroid colony-forming units (CFU-E) (T cell inhibitory activity) in patients with aplastic anaemia (AA) was investigated. In 11 (32.4%) out of 34 AA cases, T cell inhibition on autologous CFU-E growth was greater than that in normal individuals. In order to evaluate the mechanism of this inhibitory activity, T cell surface markers, interferon (IFN) production in peripheral blood mononuclear cell (PBMNC) liquid culture, and cytokine levels such as IFN and tumour necrosis factor-alpha (TNF-alpha) in CFU-E clot cocultured with T cells, were measured in a portion of the patients. In five patients investigated for IFN production in PBMNC liquid culture, all produced statistically more IFN activity than normal individuals under phytohaemagglutinin (PHA-P) stimulation (P less than 0.01) with no relation to T cell inhibitory activity. In only one patient whose T cells displayed increased CD8 and HLA-DR antigen (CD8+HLA-DR+) and inhibitory activity, a significant amount of IFN-gamma was observed in CFU-E clot cocultured with T cells, and the addition of anti-IFN gamma antibody to the coculture resulted in recovered CFU-E colony growth. These results suggest that IFN-gamma production by T cells may explain, at least in part, the pathogenesis of haematopoietic defects in AA. In other patients however, T cell inhibitory activity neither correlated to the T cell subpopulations (CD4+/CD8+, CD8+HLA-DR+), IFN production in PBMNC liquid culture, nor to IFN and TNF-alpha levels in CFU-E clot culture. The roles played by cytokines other than IFN and TNF-alpha on haematopoietic precursor cells require further evaluation in a larger sample of patients with AA. PMID- 1908314 TI - The use of the GnRH analogue buserelin for IVF--does it improve fertility? AB - OBJECTIVE: To determine the effect of a short course of the GnRH analogue buserelin and human menopausal gonadotrophin (hMG), for ovarian stimulation in our IVF programme, on reproductive endocrinology and pregnancy rates compared with conventional clomiphene citrate and hMG treatment. DESIGN: Prospective randomized allocation to one of two ovulation stimulation regimens. SETTING: Fertility clinic. SUBJECTS: 373 infertile couples with various factors associated with their subfertility. All the women were less than 46 years of age and had normal menstrual cycles. INTERVENTION: The first group (n = 151) was given clomiphene citrate (CC) from days 2-6 of the menstrual cycle and hMG from day 5 onwards (CC/hMG). The second group (n = 222) was given buserelin from days 1-3 and hMG from day 2 (buserelin/hMG). MAIN OUTCOME MEASURES: Concentration of plasma luteinizing hormone (LH), oestradiol (E2) and progesterone, number of ovulatory follicles induced and the occurrence of pregnancy. RESULTS: Plasma LH, E2 and progesterone concentrations were reduced in the late follicular phase after buserelin/hMG compared with CC/hMG. Buserelin/hMG promoted the development of more follicles than CC/hMG. The overall pregnancy rate after buserelin/hMG was not significantly different from that following CC/hMG treatment. CONCLUSION: The chance of pregnancy is not improved by the short-term use of buserelin with hMG, provided adequate follicular phase management is maintained. PMID- 1908316 TI - Gorlin's syndrome and von Recklinghausen's disease occurring in one family. AB - A family is presented in which both Gorlin's Syndrome (Basal Cell Naevus Syndrome) and von Recklinghausen's neurofibromatosis have been inherited. The features and treatment of these syndromes are discussed and the management of families with these diseases is considered. PMID- 1908315 TI - Interferon-gamma and tumour necrosis factor induce expression of major histocompatibility complex antigen on rat retinal astrocytes. AB - Cultured rat retinal astrocytes were tested by indirect immunofluorescence staining for their ability to express class I and II major histocompatibility complex (MHC) antigens under basal culture conditions and after three days of stimulation with two recombinant cytokines, rat interferon-gamma (IFN-gamma) and human tumour necrosis factor alpha (TNF alpha). Under basal culture conditions low levels of class I antigens were detected on a small percentage of cells, but there was no visible class II. IFN-gamma and TNF alpha stimulation enhanced class I expression. TNF alpha had no effect on class II expression, whereas IFN-gamma induced the expression of class II in a dose dependent manner. These findings suggest that retinal astrocytes might play a part in immunological events occurring in the retina. PMID- 1908318 TI - Rapid and simultaneous determination of zidovudine and its glucuronide metabolite in plasma and urine. Application to the pharmacokinetic interaction of zidovudine and probenecid in the monkey. PMID- 1908317 TI - A simple photokinetic method for the determination of nitroprusside in biological and pharmaceutical samples. AB - A simple method has been developed for the determination of nitroprusside in human serum and pharmaceutical preparations. The new method is based on the strong inhibitory effect of nitroprusside on the photochemical reduction of phloxin by ethylenediaminetetra-acetic acid. The rate measurements are accomplished very simply by measuring the time needed for the absorbance to be reduced to 1/10th of its initial value. Optimal conditions for the determination of nitroprusside at concentrations of 15-200 ng ml-1 are described. PMID- 1908319 TI - [Substrate specificity of the serine proteinase from Bacillus subtilis, strain 72]. AB - A comparative study of the hydrolysis of various p-nitroanilide substrates (Z-A2 A1-pNA, Z-A3-A2-A1-pNA, and Z-A4-A3-A2-A1-pNA, where A1-An are various amino acid residues, Z is the benzoyloxycarbonylic group and pNA is the p-nitroanilide group), catalyzed by serine proteinase from Bacillus subtilis strain 72, was carried out. It was found that depending on the substrate structure, the hydrolysis may involve both the peptide-p-nitroaniline and the amino acid-amino acid bonds. A kinetic analysis of substrate hydrolysis occurring simultaneously at these two bonds was carried out. The physico-chemical meaning of the kinetic parameters of the given scheme was determined. The quantitative estimation of the enzyme specificity with respect to both hydrolyzing bonds can be found by using the parameters calculated during the analysis of the kinetic curve of p nitroaniline production. It was found that according to their specificity the amino acid residues at position A1 can be arranged in the following order: L-Leu greater than P-Phe greater than L-Ile greater than L-Ala. The beta-branched amino acid residues, L-Val and L-Ile, do not bind to subsite S1. If these residues occupy position A1, the substrate splitting occurs exclusively between residues A1 and A2. The tetrapeptide N-protected p-nitroanilide substrates are also hydrolyzed at this bond. Partial hydrolysis of the amino acid-amino acid bond between residues A1 and A2 occurs in two cases: i) when residue A1 is loosely bound to subsite S1 and/or, ii) when residue A2 is firmly bound to subsite S1. PMID- 1908320 TI - [Gangliosides modulate lipoxygenase oxidation in human lymphocytes]. AB - Using reverse phase high performance chromatography with UV-detection, the arachidonic acid cascade in human peripheral blood lymphocytes (PBL) was studied. It was found that PBL oxidized arachidonic acid via the lipoxygenase pathway, 12 hydroxyeicosatetraenoic acid (12-HETE) being the major metabolite of endogenous arachidonic acid. Exogenous arachidonic acid added to human PBL suspensions increased 12-HETE synthesis 5-7 times. In another experimental series the effects of gangliosides (GD3, GM1 and GM3) on lipoxygenase-catalyzed oxidation of arachidonic acid in human lymphocytes were investigated. All the gangliosides tested stimulated PBL to secrete 12-HETE both from endogenous and exogenous arachidonic acid. In most cases the stimulating effect of GD3 was much more apparent that those of GM1 and GM3. PMID- 1908322 TI - Induction of leukemia inhibitory factor secretion by interleukin-1 in a human T lymphoma cell line. AB - The control of leukemia inhibitory factor (LIF) secretion by interleukin-1 (IL-1) was studied in the HSB2 human T lymphoma cell line. We show that in the presence of phytohemagglutinin (PHA), the addition of IL-1 in the culture medium induced a strong increase in the level of secreted LIF, as detected with the DA1.a test cell line. Subclones of the HSB2 cell line obtained by limiting dilution, and selected for their high level of LIF secretion, after phorbol myristate acetate (PMA) treatment, were more carefully analyzed. In the same conditions of stimulation, a 50X increase in the amount of secreted LIF was observed with the 2B3 subclone, whereas the 3C2 subclone gave a very weak signal in response to the stimulation. Several other chemical reagents and a panel of recombinant cytokines including IL-2, -3, -4, -5, and -6, granulocyte monocyte colony-stimulating factor (GM-CSF), monocyte-CSF (M-CSF), tumor necrosis factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma) were tested for their induction of LIF secretion. None of the other tested components was as potent as IL-1 (100 U/ml) and 1% PHA. A half maximal response was obtained with a concentration of 15-20 pM IL-1. PMID- 1908321 TI - Cure with low-dose total-body irradiation of the hematological disorder induced in mice with the Friend virus: possible mechanism involving interferon-gamma and interleukin-2. AB - The effects of split low-dose total-body irradiation (TBI; 150 cGy) on production of interferon (IFN)-gamma and Interleukin-2 (IL-2) and on the growth characteristics of erythroid progenitor cells (BFU-E) have been assessed in normal mice, normal mice receiving TBI only, mice infected with the polycythemia inducing strain of the Friend virus complex (FVC-P), and FVC-P infected mice receiving 150 cGy TBI on days 5 and 12. It was found that lymphocytes from the spleens of TBI-treated mice previously infected with FVC-P produced in response to phytohemagglutinin (PHA) and concanavalin A (Con A) stimulation up to 15 times greater amounts of IFN-gamma than cells from untreated FVC-P-infected mice. IL-2 production in Con A-stimulated spleen cell cultures also increased when cells were isolated from FVC-P-infected mice treated by low-dose TBI compared to untreated FVC-P-infected mice. TBI treatment was associated with greater than 99% ablation of "erythropoietin-independent" BFU-E colony formation. The results suggest that the cure of FVC-P-infected mice by low-dose TBI may result from activation of the IFN-gamma system and IL-2 production. PMID- 1908323 TI - Glycogen and enzymes of glycogen metabolism in rat embryos and fetal organs. AB - Glycogen content and the enzymes of glycogen metabolism have been measured in the postimplantation rat embryo over a period ranging from 9.5 to 18.5 days of gestation. The earliest periods studied were at days 9.5 and 10.5 of gestation, when the yolk sac becomes vascularized and heart beat is first established. The next intervals were at days 10.5-11.5 when vascular connections via the allantoic placenta are formed. At 14.5 and 18.5 days of development, 4 entire organs were analyzed; heart, liver, kidney and brain. The metabolic apparatus of glycogen metabolism was concentrated in the embryo at 10.5 days, then the heart region, and in the heart itself at later stages. PMID- 1908324 TI - Internal jugular venous oxygen saturation does not reflect sagittal sinus oxygen saturation in piglets. AB - Can blood samples from the internal jugular vein (IJ) be used reliably in place of sagittal sinus (SS) samples in the calculation of cerebral oxygen extraction? To test this question we compared the O2 saturation (Sat) of blood samples drawn from SS, IJ vein, and pulmonary artery (MV) during hypercarbia, eucarbia and hypocarbia in 7 paralyzed, ventilated piglets. Cerebral blood flow was assessed by measuring unilateral internal carotic artery blood flow (ICABF), determined by an electromagnetic flow probe placed around the common carotid artery after ligation of the external carotid artery. During hypocarbia, eucarbia and hypercarbia SatSS (37.3 +/- 9.3, 48.9 +/- 10.2, 70.8 +/- 11.8%, respectively) was significantly different from SatIJ (54.8 +/- 8.9, 54.5 +/- 9.0, 62.0 +/- 15.1%) and SatMV (55.9 +/- 5.5, 58.7 +/- 5.3, 53.5 +/- 11.2%). The mean slope of the SatSS vs. PaCO2 regression lines was +0.583 +/- 0.303%/mm Hg, significantly greater than the mean slope of the regression lines for SatIJ vs. PaCO2 (+0.087 +/- 0.310%/mm Hg) or SatMV vs. PaCO2 (-0.112 +/- 0.230%/mm Hg). The relationship of ICABF vs. PaCO2 (mean slope = 0.444 +/- 0.294 ml/min/mm Hg) was statistically significant, while the relationship of cardiac output (determined by an electromagnetic flow probe placed around the pulmonary artery) vs. PaCO2 (mean slope = 0.470 +/- 1.617 ml/min/mm Hg) was not. We conclude that blood samples from the IJ do not reliably reflect cerebral venous blood and cannot be substituted for SS samples in piglets. It is most probable that the substitution of IJ for SS blood is not valid in piglets because the IJ receives venous effluent from noncerebral tissue. PMID- 1908325 TI - Effect of maternal administration of thyrotropin-releasing hormone or DN1417 on functional and morphologic fetal rabbit lung maturation and duration of survival after premature delivery. AB - Though maternal treatment with thyrotropin-releasing hormone (TRH) for prevention of hyaline membrane disease has been utilized, precise mechanisms of TRH in accelerating fetal lung maturation remain unclear. We studied the effect of maternally administered TRH or DN1417 (an analog of TRH) on functional and morphologic fetal rabbit lung maturation and the duration of survival after premature delivery. Because DN1417 retains the neurotransmitter but not the neuroendocrine effects of TRH, this study enables us to determine which of these effects was responsible for enhancement of lung maturation. TRH or DN1417 (0.2 mg/kg/dose) or saline was injected intravenously into New Zealand White rabbit does 48, 36, 24, 12 and 2 h prior to sacrifice on day 27 of gestation. Functional pulmonary maturity was assessed by pressure-volume hysteresis, and morphologic maturity was assessed by histologic technique. Maternal administration of TRH or DN1417 enhanced both functional and morphologic fetal lung maturation as well as the duration of neonatal survival after premature delivery. We propose that the effect of TRH in fetal lung maturation is due to neurotransmitter rather than neuroendocrine effects. PMID- 1908326 TI - Apolipoprotein A-I-containing lipoproteins in human umbilical cord blood. Relation to proapolipoprotein A-I and lecithin:cholesterol acyltransferase. AB - Lipids, apolipoproteins, lipoproteins, as well as lipoproteins containing both apo A-I and apo A-II (Lp A-I:A-II) or apo A-I but no apo A-II (Lp A-I), proapolipoprotein (proapo) A-I and the activity of lecithin:cholesterol acyltransferase (LCAT), were investigated in umbilical cord sera of 67 term human neonates (30 females and 37 males). Lp A-I and Lp A-I:A-II were present in umbilical cord sera with levels of 0.26 +/- 0.1 and 0.33 +/- 0.15 g/l, respectively. Furthermore, the absolute amount of proapo A-I was lower in cord blood than in adult plasma, but in view of the lower apo A-I levels in umbilical cord sera it comprised 10.48 +/- 3.86% of total apo A-I and was thus significantly higher than in adult plasma (7.1 +/- 0.9%). Proapo A-I was highly correlated with HDL cholesterol and apo A-I. Total serum LCAT activity was about 50% of adult plasma and was highly correlated with Lp A-I, but not with Lp A-I:A II. We conclude that human umbilical cord serum contains both Lp A-I and Lp A-I:A II particles and that the LCAT activity is predominantly related with the Lp A-I subfraction. The higher percentage in umbilical cord sera of proapo A-I may indicate a higher turnover of apo A-I or a lower activity of the proapo A-I cleaving enzyme which is still not identified. PMID- 1908327 TI - Effect of blood transfusion on acid base, glucose and electrolyte status in very low birth weight infants. AB - The effect of citrate phosphate dextrose (CPD) blood transfusion on the acid base, glucose and electrolyte status of VLBW infants was studied in infants aged 1-7, 8-20 and greater than 20 days; a 4th group composed of infants greater than 20 days subjected to a second transfusion was also studied. All the infants remained clinically well during and after the transfusion. Only the infants in the group 1-7 days experienced a significant fall in ionic Ca and PO2. No significant change in all the other parameters studied was observed. In the other groups of infants studied, the changes observed were not significant, and became less with increasing age and repeat transfusion. VLBW infants apparently tolerate CPD blood transfusion well. PMID- 1908328 TI - Blockade of cholinergic muscarinic receptors by pirenzepine and GHRH-induced GH secretion in the acute and recovery phase of anorexia nervosa and atypical eating disorders. AB - In view of the important role played by the cholinergic system in the neural regulation of growth hormone (GH) secretion, the ability of pirenzepine, a selective antagonist of muscarinic cholinergic receptors, to blunt the GH response to GH-releasing hormone (GHRH) was studied in adolescent females with anorexia nervosa in the acute (AN-AP) five AN-AP patients, administration of GHRH 1-40 (1 microgram/kg IV) evoked a significantly higher GH response than in controls at established intervals, whereas in eight AN-RP and seven AED patients it was higher than in controls at only one (150-min) and two (150-min, 180-min) time intervals, respectively. In the AN-AP patients, pretreatment with pirenzepine (0.6 mg/kg IV) only partially blocked the GH response to GHRH, whereas in the same AN-AP patients tested during recovery, and in AN-RP and AED patients, the drug completely suppressed the GH response to GHRH, as it did in controls. In view of pirenzepine's mechanism of action, these findings are best explained by the existence in the hypothalamus of AN-AP patients of a cholinergic hypertone and/or a diminished somatostatinergic function. Evaluation of the clinical and hormonal characteristics of the anorectic patients studied would indicate that factors other than undernutrition and its biological consequences, which subside in the recovery stage of the disease and are not present in AED patients, contribute to the anomalous GH response pattern of AN-AP patients. PMID- 1908329 TI - Differential actions of corticosterone on luteinizing hormone and follicle stimulating hormone biosynthesis and release in cultured rat anterior pituitary cells: interactions with estradiol. AB - Previous in vivo studies from our laboratory suggested that glucocorticoids antagonize estrogen-dependent actions on LH secretion. This study investigated whether corticosterone (B) may have similar actions on gonadotropin biosynthesis and secretion in vitro. Enzymatically dispersed anterior pituitary cells from adult female rats were cultured for 48 h in alpha-modified Eagle's medium containing 10% steroid-free horse serum with or without 0.5 nM estradiol (E2). The cells were then cultured for 24 h with or without B in the presence or absence of E2. To evaluate hormone release, 5 x 10(5) cells were incubated with varying doses of GnRH (0, 10(-11)-10(-7) M) or pulsatile GnRH (10(-9) M; 20 min/h) for 4 h. Cell and medium LH and FSH were measured by RIA. To evaluate LH biosynthesis, 5 x 10(6) cells were incubated for an additional 24 h with 10(-10) M GnRH, 60 microCi 3H-glucosamine (3H-Gln), 20 microCi 35S-methionine (35S-Met), and the appropriate steroid hormones. Radiolabeled precursor incorporation into LH subunits was determined by immunoprecipitation, followed by SDS-PAGE. Continuous exposure to GnRH stimulated LH release in a dose-dependent manner, and this response was enhanced by E2. B by itself had no effect on LH release, but inhibited LH secretion in E2-primed cells at low concentrations of GnRH (10(-10) M or less). Total LH content was not altered by GnRH or steroid treatment. Similar effects of B were observed in cells that were given a pulsatile GnRH stimulus. In contrast to LH, E2 or B enhanced GnRH-stimulated FSH release at the higher doses of GnRH, while the combination of E2 and B increased basal and further augmented GnRH-stimulated release. Total FSH content was also increased in the presence of B, but not E2 alone, and was further augmented in cells treated with both steroids. There were no effects of the steroids on the magnitude of FSH release in response to GnRH pulses, but the cumulative release of FSH was greater in the E2 + B group compared to controls, indicating an increased basal release. Independent of E2, B suppressed the incorporation of 3H Gln into LH by more than 50% of control, with only subtle effects on the incorporation of 35S-Met.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1908330 TI - The peripubertal golden hamster and the transition between daily and estrous cycle hormone rhythms. AB - Transitional patterns of LH, FSH, and progesterone (P4) in the circulation were studied in peripubertal female golden hamsters. A daily rhythm, with afternoon surges of these hormones, is typical of the immature female, whereas 4-day rhythms characterize the estrous cycle of the adult. Blood samples were collected repeatedly from maturing individuals at either 1400 or 1700 h. Each animal was examined daily for the appearance of regular vaginal estrous cycles as indicated by a mucous exudate on the morning of ovulation. Between Days -10 and -5 relative to first vaginal estrus (FVE), afternoon surges of LH, FSH, and P4 were often observed. From Days -5 to -1 relative to FVE, afternoon surges of LH and FSH were less frequent, but P4 retained the daily rhythmicity until Day -2. A 4-day pattern of LH secretion, but not of FSH or P4, was established prior to FVE. To determine whether or not ovulations were occurring prior to the appearance of external vaginal estrous cycles, reproductive tracts were collected from 26-34 days of age and examined for evidence of ovulation. Of 124 females, concordance between the record of daily vaginal examinations and the examinations of the ovaries and oviducts was found in 103 cases (83%). The development of ovarian follicles was correlated with FVE in peripubertal hamsters by unilateral ovariectomy. Antral follicles were found only in the last 3 days prior to vaginal estrus. PMID- 1908331 TI - Effect of estrogen administration on endogenous and luteinizing hormone-releasing hormone-induced luteinizing hormone secretion and follicular development in the lactating sow. AB - The objectives of this study were to investigate whether estradiol treatment during lactation modifies 1) the patterns of endogenous LH, FSH, and prolactin (PRL) release; 2) the sensitivity of the pituitary to exogenous injections of LHRH; and 3) the responsiveness of the ovarian follicles to gonadotropin. Plasma LH, FSH, and PRL were determined in samples taken repeatedly from 18 sows on Days 24-27 of lactation. Ovaries were then recovered, and follicular development was assessed by measuring the follicular diameter (FFD) and follicular fluid estradiol-17 beta concentration (FFE) of the ten largest follicles dissected from each ovary. Sows were randomly allocated to one of four treatments: 1) Group C (4 sows) received no treatment; 2) Group LHRH (5 sows) received 800 ng of LHRH every 2 h throughout the sampling period; 3) Group E2 (4 sows) received subcutaneous implants containing estradiol-17 beta 24 h after start of sampling; 4) Group LHRH + E2 (5 sows) were administered a combination of LHRH and estradiol-17 beta implants. Between-animal variability for plasma LH, FSH, and PRL was considerable. LH concentration and LH pulse frequency increased (p less than 0.05) after LHRH treatment in the LHRH and LHRH + E2 groups; however, an acute inhibition of LH secretion was observed in the latter group immediately after estradiol implant application. In the absence of LHRH treatment, estradiol caused chronic inhibition of LH secretion. Follicular development was greater in the LHRH and LHRH + E2 groups compared to the C and E2 groups (p less than 0.05 for both FFD and FFE).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1908332 TI - Effects of steroid administration on pituitary luteinizing hormone and follicle stimulating hormone in ovariectomized pony mares in the early spring: pituitary responsiveness to gonadotropin-releasing hormone and pituitary gonadotropin content. AB - These experiments tested the hypothesis that administration of steroid hormones to ovariectomized (OVX) mares during the vernal transition to the breeding season would influence LH and FSH secretion. Circulating gonadotropin concentrations, response to exogenous GnRH, and pituitary gonadotropin content were monitored. Experiments 1 and 2 were conducted, beginning 10 March, and 3 February, respectively, utilizing a total of 30 long-term OVX pony mares. In experiment 1, mares were administered vehicle (n = 5) or estradiol-17 beta (E2, n = 5, 5 mg/3 ml sesame oil), twice daily for 16 days. Blood samples were collected daily for assessment of circulating LH and FSH concentrations. On Day 10 of treatment, 400 micrograms GnRH were administered to all mares. LH increased significantly over days of treatment in the estradiol-treated group, but pituitary response to GnRH tended to be less than in control mares. Circulating FSH tended to decline over days of treatment in estradiol-treated mares, and the pituitary response to GnRH was significantly reduced. Pituitary LH, but not FSH, was increased on Day 16 of treatment with estradiol. In experiment 2, 20 OVX mares received, twice daily, vehicle (n = 5), E2, n = 5; 5 mg), progesterone (P4, n = 5; 100 mg), or progesterone plus estradiol (P4/E2, n = 5; 100 + 5 mg). Treatment continued for 14 days. GnRH (100 micrograms) challenges were administered on Days 6 and 13 of treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1908333 TI - [Total parenteral nutrition of neurosurgical patients following elective midline surgery]. AB - The authors report on their results of total parenteral nutrition (TPN) which was performed in a group of 11 comatose patients following elective neuro-surgery of different midline lesions (e.g. tumours, aneurysms of the anterior communicating artery). Carbohydrates were administered from day 1 postoperatively in a dose of 18-24 kcal/kg BW/day. Amino acids were given as a commercially available 12.5% solution (1.4-1.83 g/kg BW/day). Daily routine laboratory values were measured as well as levels of total serum protein, albumin, prealbumin, and retinol-binding protein. Free amino acids in plasma were measured on the day of operation and on day 3, 5, and 7 postoperatively. Renal nitrogen loss was high with maximal values up to 30 gm/day. By TPN cumulative nitrogen balance remained positive until day 2 and was reduced to -61.8 g at the end of the study period. Short-lived serum proteins remained normal. Free FAA's in plasma increased steadily with their highest levels on day 5 and 7 (twice the normal range). Besides slight elevation of liver enzymes and mild hyperglycaemia, no severe changes were observed in routine laboratory parameters. The authors conclude that severe catabolism is a common feature in comatose patients after elective midline surgery and is comparable to catabolism following brain injuries. TPN is well indicated in this group as it preserves visceral protein levels and reduces nitrogen loss without severe side effects. PMID- 1908334 TI - In vitro cytokine release by activated murine peritoneal macrophages: role of prostaglandins in the differential regulation of tumor necrosis factor alpha, interleukin 1, and interleukin 6. AB - Distinct subpopulations of macrophages or differently activated macrophages display various functions in immune reactions. Some of their activities depend on specific sets of factors (i.e., cytokines and eicosanoids) produced by activated macrophages. We have studied the ability of murine (CBA/ca) peritoneal macrophages to selectively release tumor necrosis factor alpha (TNF-alpha), interleukin 1 (IL-1), and IL-6. We have found that the priming of cells (Mo) with different stimulants (thioglycolate vs. LPS) induces the release of particular cytokines by reactivated macrophages. The increased release of TNF-alpha correlates with lower levels of IL-1 and IL-6. We have also found that prostaglandin E2 (PGE2) and prostacyclin (PGI2) have opposing effects on the production of two of these cytokines. The release of TNF-alpha is inhibited by prostaglandins, whereas increased levels of PGE2 and PGI2 correlate with higher levels of IL-6. PMID- 1908335 TI - EM analysis of Drosophila chorion genes: amplification, transcription termination and RNA splicing. AB - We have used the electron microscope to examine ultrastructurally several events occurring during the biogenesis of two very abundant chorion (eggshell) mRNA molecules in the follicle cells of Drosophila melanogaster--namely, selective gene amplification, transcription initiation and termination, and RNA processing. We find that the highly transcribed s36 and s38 genes are positioned in the central region of large, multi-forked amplified DNA structures. Transcript morphology is consistent with the known presence of a small intron at the 5' end of each gene. Mature transcripts are associated with spliceosomes, demonstrating that splice site selection occurs co-transcriptionally but that splicing is completed after transcript release from the template. We have also mapped the termination sites for the genes. The two genes exhibit efficient termination very near their poly(A) sites--within a 210 bp region for s36 and a 360 bp region for s38. PMID- 1908336 TI - Human anti-murine immunoglobulin responses and immune functions in cancer patients receiving murine monoclonal antibody therapy. AB - In our institution, over 200 patients with gastro-intestinal tract carcinomas have been treated with monoclonal antibodies (MAbs) including CO 17-1A. In one clinical trial, MAbs were administered in combination with gamma interferon. Natural killer cell cytotoxicity (NK) and antibody-dependent cell-mediated cytotoxicity (ADCC) were studied in patients before treatment. Very low NK and ADCC activities were measured in metastatic cancer patients. NK cell lysis was enhanced during gamma-interferon treatment, associated with a modification of the Fc receptor expression, but no changes in the ADCC reactivities of leukocytes were noticed. Monoclonal antibodies were circulating for one to four weeks after a single dose infusion, independent of the patients' immune responses toward the administered MAb. Sixty-three percent of the patients mounted an anti-mouse immunoglobulin response. Anti-idiotypic antibodies were detected in 70% of the responding patients. Variations in the anti-mouse Ig responses were dependent on the therapeutic protocol. The immune responses were composed of IgM, IgA, and IgG (mainly IgG1, often associated with IgG2 and/or IgG3). In patients receiving MAbs together with gamma-interferon, development of the anti-mouse Ig responses were delayed with an increase in the anti-isotypic component and a decrease in the anti-idiotypic component as compared to patients treated with MAb alone. No correlation could be established with clinical results. PMID- 1908337 TI - Characterization of WR-1065 absorption in the rat small intestine. AB - A circulating in situ rat small intestine absorption model was used to study the lumenal metabolism and absorption of [14C]WR-1065. WR-1065 was found to be more tissue reactive and toxic than its phosphorylated form, ethiofos, at equimolar perfusate concentrations. The disappearance profiles of the radiolabeled drug and free WR-1065 indicate that WR-1065 is extensively metabolized in the intestinal lumen prior to absorption. Coadministration of disodium ethylenediaminetetraacetic acid enhances the absorption of the free thiol although not to the same extent as seen with ethiofos. Perfusion of WR-1065 in citrate buffer decreased lumenal degradation of the drug but resulted in decreased absorption. The total material converted to WR-1065 portal blood profiles following ethiofos and WR-1065 perfusion were altered possibly due to distribution and metabolism differences. This study coupled with earlier work completed on ethiofos have increased our understanding of the significant barriers to absorption observed following oral administration of these compounds. PMID- 1908338 TI - Metabolism of 14C-2',3'-dideoxyinosine by the in situ perfused rat liver preparation. AB - The metabolism and biliary excretion of 14C-dideoxyinosine (14C-ddI) has been investigated using the in situ perfused rat liver (PRL) preparation. After 2 h of perfusion through the liver, approximately 70-75 per cent of the total 14C radiolabel was recovered in the perfusion medium, less than 1 per cent was excreted in bile and 15-18 per cent was retained in the liver. Hepatic clearance of ddI was 1.5 +/- 0.1 ml min-1 and half-life for the elimination of ddI from the medium was 22.9 +/- 2.0 min (n = 3). Hepatic extraction was estimated to be 7.5 per cent. HPLC analysis of the effluent perfusate indicated that ddI was metabolized to hypoxanthine, xanthine, uric acid, and to a polar metabolite which was tentatively identified as allantoin. Approximately 60-65 per cent of the ddI dose was converted to allantoin after 2 h of perfusion. Of the other three metabolites, uric acid levels increased to 20-30 per cent of the dose after 45 min and declined to about 5 per cent of the dose by the end of the perfusion period. Levels of hypoxanthine and xanthine were low and both compounds were not detected in the perfusate after 45 min post-infusion. In bile, the major peak, which accounted for about 50 per cent of the 14C-radiolabel co-eluted with the putative metabolite, allantoin (0.4 per cent of the dose). Uric acid (0.06 per cent of the dose) was the only other metabolite detected in bile. These results suggest that biliary excretion is a minor pathway for the elimination of ddI. Furthermore, ddI is rapidly cleared and metabolized by the liver to hypoxanthine, xanthine, uric acid, and to allantoin. PMID- 1908339 TI - Changes in cerebrospinal fluid pressure and spinal cord perfusion pressure prior to cross-clamping of the thoracic aorta in humans. AB - Little is known about what influences cerebrospinal fluid pressure (CSFP) during anesthesia prior to aortic cross-clamping (AXC). Therefore, this study measured the effect of anesthetic induction, of various drugs administered during the course of surgery prior to AXC, and of hemodynamic changes on CSFP, and calculated spinal cord perfusion pressure (SCPP = mean arterial pressure [MAP] - CSFP) in 11 patients undergoing surgery on the descending thoracic aorta. A lumbar drainage catheter was placed to facilitate drainage of CSF and to measure CSFP. Anesthesia was induced with fentanyl, 50 micrograms/kg, and midazolam, 1 mg, using a pancuronium-metocurine mixture for neuromuscular blockade. Data were collected prior to and after (1) anesthetic induction, (2) mannitol to augment diuresis, (3) sequential use of sodium nitroprusside (SNP) and isoflurane (ISO) to lower MAP by 20%, (4) drainage of spinal fluid, (5) intrathecal injection of papaverine (IP), and (6) AXC. Statistical comparisons of recorded data were made using the least squares mean method and Friedman test. Linear regression was used to test for correlation between CSFP and hemodynamics. Anesthetic induction affected neither hemodynamics nor CSFP. Mannitol significantly increased heart rate, central venous pressure (CVP), pulmonary capillary wedge pressure (PCWP), cardiac output (CO), and CSFP (P less than 0.05). SNP or ISO altered neither CVP, PCWP, CO, nor CSFP, which remained elevated at the postmannitol infusion level. ISO, unlike SNP, caused a significant decrease in SCPP (P less than 0.005). Subsequent drainage of 20 mL of CSF improved SCPP (P less than 0.05). IP did not have any effect on hemodynamics or CSFP. CSFP showed a strong correlation with CVP (r = 0.86).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1908340 TI - Hepatic veno-occlusive disease post-bone marrow transplantation in children conditioned with busulfan and cyclophosphamide: incidence, risk factors, and clinical outcome. AB - We performed a retrospective analysis of the incidence, risk factors, and clinical outcome of hepatic veno-occlusive disease (VOD) in 50 children prepared for bone marrow transplantation with busulfan (16 mg/kg) and cyclophosphamide (200 mg/kg). The overall incidence of VOD was 28% (14/50). The incidence of VOD among patients transplanted for leukemia was 36% (14/39). In contrast, no patient transplanted for a genetic disease developed VOD. Neither patient age, sex, remission status, type of graft (i.e. allogeneic or autologous), past history of liver disease nor pretransplant liver function tests were associated with an increased risk of VOD. In addition, 23 of 50 patients had pretransplant samples available for antihepatitis C virus (HCV) testing; 3/23 were reactive (two of nine patients with VOD and one of 14 patients without VOD were positive for anti HCV). We found a high incidence of pleural effusion in patients with VOD (7/14), an association that has previously not been described. VOD was manageable and resolved in all patients. PMID- 1908341 TI - Brain injury: analysis of outcome in a post-acute rehabilitation system. Part 2: Subanalyses. AB - The basic findings of brain-injured patients who underwent treatment within a co ordinated system of post-acute brain-injury rehabilitation programmes have already been reported. The changes in function during the course of treatment by this post-acute sequence of rehabilitation were obtained and reported. A defined total population of N = 192 was examined, with exclusions for appropriate causes (e.g. patients seen only for evaluation) producing a study population of N = 173; of these, follow-up was achieved in 145 cases, a follow-up rate of 83.8%. Time from date of injury to date of admission, severity of deficit at time of admission to programme, and other appropriate independent variables were used to characterize the population. A single-blind interview methodology was employed in obtaining dependent measures of outcome at 6, 12 or 24 month periods post discharge. Measures of outcome included residential status, level of productivity activity, and hours per day of attendant care or supervision required. In the work reported in this paper dependent variables are analysed for various subgroups of the total population. The subgroups analysed are: patients with traumatic brain injury only; mild moderate and severe grades of disability; and comparisons of outcomes at 6 months, 1 year, and 2 years post-discharge from treatment. The results are presented in terms of percentage change in dependent measures from point of admission to follow-up. Appropriate parametric and non parametric statistical analyses of significance are carried out. Additionally, an analysis of cost associated with treatment, and some analysis of cost-benefit is provided. The results document substantial improvements in function during post acute rehabilitation for both traumatic brain injury and brain dysfunction of other etiologies. Significant improvements are seen to occur in all grades of severity of dysfunction examined, and such improvements are robust and persist without evidence of decrement over the 2-year follow-up period. In addition, economic considerations suggest the potential for the recouping of costs of treatment within a reasonable period of time. PMID- 1908342 TI - Compulsory psychiatric treatment in the community. I. A controlled study of compulsory community treatment with extended leave under the Mental Health Act: special characteristics of patients treated and impact of treatment. AB - Following in-patient psychiatric treatment under Section 3 of the Mental Health Act, some patients have in the past remained on Section after discharge, and subsequently the Section has been renewed while the patient remained 'on leave'. People treated thus with 'extended leave' probably resemble closely those who would be placed on a community treatment order if this were available. A group of these extended-leave patients was compared with a control group, matched for age, sex and diagnosis, selected by consultant psychiatrists as not requiring treatment using a community treatment order. The two groups showed very few differences, but the extended-leave patients more commonly had a history of recent dangerousness and non-compliance with psychiatric treatment. Use of extended leave improved treatment compliance, reduced time spent in hospital, and reduced levels of dangerousness. PMID- 1908343 TI - Day care in an inner city. I. Characteristics of attenders. AB - The socio-demographic and clinical characteristics of patients attending psychiatric day care in an inner-urban catchment area were assessed using structured techniques. The overall prevalence of the use of day care was high (164 per 100,000 total population), and 86% of attenders were in prolonged psychiatric contact. Of those in prolonged contact, the clinical and social morbidity of 68 attenders at National Health Service day hospitals was strikingly similar to that of 42 attenders at other units. Users of a 'community mental health centre' and two work centres were less disabled than attenders at other day units. Implications of these results for the organisation of day services and training of staff are discussed. PMID- 1908344 TI - Day care in an inner city. II. Quality of the services. AB - Seven units providing psychiatric day care to residents of an inner-city area were surveyed. The extent to which the clinical and special problems of attenders were adequately managed by the services was measured using a 'needs-assessment' technique. Units differed in the proportion of clinical and social problems that were rated as 'unmet needs', although the extent of 'unmet need' was not clearly related to the morbidity of attenders at a unit or the available staffing. PMID- 1908345 TI - An innovative method for neuraxis radiotherapy using partial transmission block technique. AB - Whole CNS (neuraxis) radiotherapy is an important part of therapy for certain CNS tumours which seed via the CSF. Many, if not the majority, of these predominantly young patients are cured but the neuropsychometric, neuroendocrine and growth morbidity of neuraxis radiotherapy on children by conventional methods may be considerable; patients receiving such therapy at an early age often are eventually in the educationally subnormal category. Recent radiobiological data support the concept that all aspects of CNS radiation tolerance are heavily dependent on daily fraction size. We describe a new radiotherapy technique that allows lower daily fraction sizes to be delivered to the neuraxis without prejudicing the total dose to the neuraxis or primary area and without prolonging the overall treatment time. Published radiobiological data support the concept that all the major morbidities attributed to conventional neuraxis radiotherapy will be reduced by the currently described technique without reducing tumour control rates. PMID- 1908346 TI - Treatment of recurrent urethral strictures using clean intermittent self catheterisation. AB - The treatment of urethral strictures has been greatly improved by the use of the optical urethrotome. However, there remains a group of patients with recurrent strictures for whom the alternatives remain long-term dilatation/urethrotomy or urethroplasty. Over the last 3 years we have treated 65 such patients using clean intermittent self-catheterisation as a method of self-dilatation. This has resulted in a dramatic decrease in the number of operations performed on these patients, with no significant reduction in urinary flow rate over an average follow-up period of 20 months. The method offers the possibility of long-term cure and should be offered to all all such patients, reducing still further the number of patients who require urethroplasty. PMID- 1908347 TI - Streptococcus bovis septicaemia associated with uncomplicated colonic carcinoma. PMID- 1908348 TI - Inhibition of glucuronidation of benzo(a)pyrene phenols by long-chain fatty acids. AB - Long-chain fatty acids inhibit glucuronidation of benzo(a)pyrene phenols in perfused liver; therefore, this study was designed to investigate interactions of fatty acids with beta-glucuronidase, glucuronosyl transferase, and energy supply. In beta-glucuronidase-deficient C3H/He mice, infusion of oleate (250 microM) increased the release of free benzo(a)pyrene phenols from 14 to 33 nmol/g/h and decreased release of glucuronides into the perfusate from 25 to 17 nmol/g/h. Rates of accumulation of glucuronides in the liver were also diminished from 11 to 4 nmol/g/h after infusion of oleate (250 microM). Fatty acids did not affect the release of benzo(a)pyrene metabolites into bile, and the ratio of free phenol to glucuronide production was increased from 0.57 to 1.30. A similar trend was observed in livers from DBA/2 mice that have beta-glucuronidase. Rates of hydrolysis of benzo(a)pyrene-O-glucuronide were not altered in isolated microsomes by addition of oleoyl coenzyme A (CoA) or octanoyl CoA (10- approximately 100 microM). Thus, we conclude that fatty acids do not alter glucuronidation by acting on beta-glucuronidase. The concentration of cofactors (UDP-glucuronic acid, UDP-glucose, and adenine nucleotides) involved in hepatic conjugation was not altered by infusion of concentrations of oleate (300 microM) that inhibited glucuronidation in perfused livers. When oleate concentrations were increased to 600 microM, UDP-glucuronic acid and UDP-glucose decreased 44 and 49%, respectively, and the ATP:ADP ratio declined concomitantly. Oleoyl CoA inhibited UDP-glucuronosyl transferase noncompetitively (half-maximal inhibition, 10 microM) in microsomes with 3-hydroxy-benzo(a)pyrene or p-nitrophenol as substrate. In contrast, octanoyl CoA was a very poor inhibitor of transferase activity. Inhibition of the transferase by oleoyl CoA was increased markedly by treatment with detergents (Triton X-100), i.e., half-inhibition of glucuronosyl transferase was obtained with about 2 microM oleoyl CoA. Inhibition of UDP glucuronosyl transferase by oleoyl CoA was also increased in a dose-dependent manner by albumin, possibly due to increasing access of the CoA derivative to the enzyme. Collectively, these data indicate that fatty acids diminish glucuronidation via the formation of acyl CoA compounds that inhibit UDP glucuronosyl transferase noncompetitively. PMID- 1908349 TI - Effect of the Bowman-Birk protease inhibitor on the expression of oncogenes in the irradiated rat colon. AB - In this study, we tested the influence of i.p. Bowman-Birk protease inhibitor (BBI) administration on oncogene expression in unirradiated and irradiated rat colonic mucosa. Total cellular RNA was collected from the colonic mucosa, and the levels of c-myc, c-fos, c-Ha-ras, c-EGFR, and c-actin mRNA were examined by standard dot and Northern blot analyses. The data demonstrate that BBI is capable of preventing radiation-induced overexpression of c-myc and c-fos without interfering with the constitutive expression of these 2 genes. It was also determined that BBI did not interfere with either radiation-induced overexpression of c-Ha-ras and c-EGFR or the constitutive expression of c-Ha-ras, c-EGFR, or c-actin. The data demonstrate that the anticarcinogenic BBI selectively inhibits the overexpression of c-myc and c-fos while not affecting crypt cell proliferation. These results suggest that a protease is involved in the pathway for enhanced c-myc and c-fos expression and that protease inhibitors such as BBI can interrupt this pathway. PMID- 1908350 TI - Inhibition of 7,12-dimethylbenz(a)anthracene-induced mammary tumors and DNA adducts by dietary selenite. AB - The present studies were designed to examine the influence of dietary selenite supplementation on the initiation phase of 7,12-dimethylbenz(a)anthracene (DMBA) induced mammary carcinogenesis and to correlate selenite-induced changes in the binding of DMBA metabolites to rat mammary cell DNA with the ultimate tumor incidence. Diets formulated to contain selenium, as sodium selenite at 0.1, 0.5, 1, 2, or 4 micrograms/g were fed for 2 weeks prior to and 2 weeks following treatment with DMBA (5 mg/kg body weight). Food intake and weight gain did not differ among treatments. Tumor incidence correlated inversely to the quantity of selenium consumed (r = -0.99). Final tumor incidences were 52, 32, 24, 14, and 10% for rats fed 0.1, 0.5, 1, and 4 micrograms selenium/g, respectively. In a separate group of rats fed a diet containing 4 micrograms selenium/g during both the initiation and promotion stages the final tumor incidence was 4.8%. Selenite supplementation for 2 weeks markedly depressed the occurrence of individual and total DMBA-DNA adducts. The final mammary tumor incidence correlated positively with total DMBA-DNA adducts (r = 0.99). These studies clearly demonstrate that selenite can inhibit the initiation stage of mammary carcinogenesis. This reduction in tumor incidence is likely due to a reduction in carcinogen metabolism and ultimately adduct formation. PMID- 1908351 TI - Tumor progression of murine epidermal cells after treatment in vitro with 12-O tetradecanoylphorbol-13-acetate or retinoic acid. AB - Tumor-promoting or antipromoting agents potentially may act directly on initiated squamous epithelial cells or indirectly through effects on normal keratinocytes or immune cells. The purpose of this study was to examine direct effects by comparing in vitro and in vivo treatment of initiated cell populations with 12-O tetradecanoylphorbol-13-acetate (TPA) or retinoic acid. Keratinocytes were initiated by treatment in vitro with 7,12-dimethylbenz[alpha]anthracene. Replicate cultures of a cloned initiated cell line were exposed to TPA or retinoic acid with acetone as control. After an equivalent number of population doublings, cultured cell sheets were transplanted as skin grafts to athymic nude mice. Replicate grafts from each in vitro treatment group were then treated with TPA or retinoic acid for 8 months. Promotion was quantified by tumor incidence (graft sites with tumor per total sites) and by tumor growth rate. The findings were as follows: (a) TPA increased tumor incidence whether it was applied in vitro or in vivo; (b) TPA in vitro favored more progressive tumors than TPA in vivo; (c) stages of malignant progression from cloned keratinocytes treated in vitro were histologically identical to those following treatment of skin in vivo, including papilloma, dysplastic invasive papilloma, squamous cell carcinoma, and metastasis to lymph node and lung; (d) retinoic acid treatment in vivo reduced tumor incidence and tumor growth rate in initiated cells previously exposed to TPA but not in cells previously exposed to retinoic acid. The results indicated the following: (a) direct effects of TPA on initiated keratinocyte populations were a significant component of tumor promotion; (b) factors in vivo modified the TPA response toward less progressive growth; and (c) the effect of retinoic acid was modulated by prior treatment history. PMID- 1908352 TI - Effect of inflammatory cytokines on the adherence of tumor cells to endothelium in a murine model. AB - We have demonstrated that pretreatment of mouse brain microvascular endothelial cells (MBE) with tumor necrosis factor-alpha (TNF), IL-1, or LPS augmented the binding of P815 mastocytoma cells in vitro. The effect of these agents was dose and time dependent. PMA was able to mimic the influence of these factors to a limited degree. The effect of TNF on endothelium was accompanied by the appearance of changes in the expression of proteins isolated from endothelial cell membranes. The adherence of tumor cells to endothelium was not inhibited by RGD-containing peptides but could be decreased by preincubation of endothelium with high concentrations of FCS. Our data suggest that cytokines regulate the synthesis of endothelial adhesion proteins which may be involved in tumor cell adherence leading to metastasis. These results raise the possibility that cytokines may exert paradoxical effects in vivo, i.e., a cytotoxic effect that reduces tumor mass accompanied by a metastasis-enhancing effect that actually promotes dissemination of the remaining tumor cells. Definition of the molecular events involved in tumor cell-endothelial cell interactions may lead to strategies for minimizing the latter effect in therapeutic settings. PMID- 1908353 TI - Mouse Hepa-1 tumor is rejected by H-2Db-restricted CTL despite decreased MHC class I antigen expression. AB - It has recently been hypothesized that tumor cells with reduced levels of MHC class I antigens are more susceptible to NK-mediated lysis and are rejected by NK cells, whereas tumor cells with normal levels of class I are rejected by tumor specific CTL. We have tested this hypothesis using a mouse hepatoma system. The Hepa-1 tumor is a spontaneous H-2Kb loss variant that arose from the BW7756 tumor, when BW7756 was adapted to growth in culture. Our studies have shown that despite the loss of H-2Kb antigen, Hepa-1 is not more susceptible to NK lysis than its H-2Kb-transfected variants. These studies also suggested that NK cells were not responsible for rejection of the Hepa-1 tumor. The Hepa-1 tumor, therefore, appears to contradict the hypothesized linkage of MHC levels and NK susceptibility. Because NK cells are not involved in immunity to this tumor, we have sought to identify the effector cell responsible for Hepa-1 rejection. Cytotoxic T lymphocyte assays demonstrate that in vitro, Hepa-1 cells are lysed by Hepa-1-specific H-2Db-restricted CD4-CD8+ T lymphocytes. Footpad assays demonstrate that in vivo, Hepa-1 rejection requires CD4+CD8- and CD4-CD8+ Hepa-1 primed splenocytes. These results indicate that immunity to Hepa-1 is T cell mediated. Hepa-1 is therefore an example of an unusual tumor in that down regulation of MHC class I antigen expression is associated with increased CTL susceptibility. PMID- 1908354 TI - ATP-regulated K+ channels protect the myocardium against ischemia/reperfusion damage. AB - The role of ATP-regulated K+ channels in protecting the myocardium against ischemia/reperfusion damage was explored using glibenclamide and pinacidil to block and activate the channels, respectively. Electrical and mechanical activity of arterially perfused guinea pig right ventricular walls was recorded simultaneously via an intracellular microelectrode and a force transducer. The preparations were subjected to either 1) 20 minutes of no-flow ischemia with or without glibenclamide (1 and 10 microM) followed by reperfusion, or 2) 30 minutes of no-flow ischemia with or without pinacidil (1 and 10 microM) followed by reperfusion. No-flow ischemia for 20 minutes produced changes in electrical and mechanical activity that were completely reversed on reperfusion; resting membrane potential declined by 13 +/- 1.2 mV, action potential duration at 90% repolarization (APD90) decreased by 62%, and developed tension fell by greater than 95%, but resting tension did not change significantly. Glibenclamide (10 microM) had no effect on activity during normal perfusion, but during ischemia, resting membrane potential fell slightly further (17 +/- 1.8 mV) and APD90 declined by only 24%. Developed tension declined more slowly and to a lesser extent, but resting tension rose significantly between 10 and 20 minutes of ischemia. Reperfusion of glibenclamide-treated tissues elicited arrhythmias (extrasystoles and tachycardia), and the preparations failed to recover mechanical function. Glibenclamide at 1 microM produced qualitatively similar effects, albeit less severe. After 30 minutes of no-flow ischemia in untreated tissues, resting tension increased by approximately 130% during the no-flow period. Reperfusion caused arrhythmias (extrasystoles, tachyarrhythmias, and fibrillation) and failed to restore resting or developed tension to preischemic levels. Pinacidil at 1 microM did not affect electrical or contractile function, but at 10 microM it had a negative inotropic effect, decreasing APD90 and developed tension by 5% and 18%, respectively. Both concentrations of the drug caused a faster and greater decline in APD90 during the no-flow period. Resting tension did not change during 30 minutes of no-flow ischemia in the presence of pinacidil, and reperfusion led to 85% and complete recovery of electrical and mechanical activity at 1 and 10 microM, respectively. The data indicate that glibenclamide enhances whereas pinacidil reduces myocardial damage caused by ischemia/reperfusion. The results are consistent with the hypothesis that activation of ATP-regulated K+ channels during ischemia is an important adaptive mechanism for protecting the myocardium when blood flow to the tissue is compromised. PMID- 1908355 TI - Sulfonylureas, ATP-sensitive K+ channels, and cellular K+ loss during hypoxia, ischemia, and metabolic inhibition in mammalian ventricle. AB - Sulfonylurea derivatives glibenclamide and tolbutamide are selective blockers of ATP-sensitive K+ (KATP) channels. However, their ability to prevent cellular K+ loss and shortening of action potential duration during ischemia or hypoxia in the intact heart is modest compared with their efficacy at blocking KATP channels in excised membrane patches. In the isolated arterially perfused rabbit interventricular septum, the increase in unidirectional K+ efflux and shortening of action potential duration during substrate-free hypoxia were effectively blocked by glibenclamide, but only by very high concentrations (100 microM); during hypoxia with glucose present, glibenclamide was only partially effective at reducing K+ loss. During total global ischemia (10 minutes), up to 100 microM glibenclamide or 1 mM tolbutamide attenuated shortening of action potential duration but only reduced [K+]0 accumulation by a maximum of 32 +/- 6%. In isolated patch-clamped guinea pig ventricular myocytes in which the whole-cell ATP-sensitive K+ current was activated by exposure to the metabolic inhibitors, glibenclamide (up to 100 microM) and tolbutamide (10 mM) were only partially effective at blocking the whole-cell ATP-sensitive K+ current (maximum block, 51 +/- 10% and 50 +/- 9%, respectively), especially when ADP was included in the patch electrode solution. In inside-out membrane patches excised from these myocytes, glibenclamide blocked unitary currents through KATP channels with a Kd of 0.5 microM and a Hill coefficient of 0.5 in the absence of ADP at the cytosolic membrane surface, but block was incomplete when 100 microM ADP (+2 mM free Mg2+) was present. ADP had a similar effect on block of KATP channels by tolbutamide. These findings suggest that free cytosolic [ADP], which rises rapidly to the 100 microM range during early myocardial ischemia and hypoxia, may account for the limited efficacy of sulfonylureas at blocking ischemic and hypoxic cellular K+ loss under these conditions. PMID- 1908356 TI - [Localization of antigen and antibodies in the liver and intestine of mice with Schistosoma japonicum]. AB - Indirect fluorescent antibody test was used to localize the antigen in the livers and intestines of mice with Schistosoma japonicum. No antigen was detected 4 weeks p.i.. There was a significant rise in antigen level 6 weeks p.i. which reached peak level 10-12 weeks p.i., the GMRT being 512 and 483, respectively. The eggs in the tissues showed strong fluorescent reaction 6 weeks p.i.. The mean diameter of schistosome egg granulomas in the livers and intestines of infected mice was remarkably enlarged 6 weeks after infection. The mean diameter of egg granulomas in the livers was markedly larger than that in the intestines. The antibodies were localized in the livers and intestines of infected mice as shown by the direct fluorescent antibody test (DFAT) and IFAT. The results indicated that the levels of IgG, IgM and IgA antibodies appeared 6 weeks p.i. which went on a significant increase at the 10-12 weeks. The IgG antibody level was higher than that of other two antibodies. It is suggested that the IgG may be the main antibody in the immunologic response of Sj egg granulomas. PMID- 1908357 TI - [Observation on the production of interleukin-1 and interleukin-2 and response to interleukin-2 in patients with schistosomiasis]. AB - The ability of adherent and nonadherent peripheral blood mononuclear cells (PBMC) from forty patients with schistosomiasis to produce IL-1 and IL-2 was studied. The results indicated that ConA-stimulated nonadherent-PBMC from patients exhibited a decreasing ability to produce IL-2 compared with controls (P less than 0.001), and that their ConA-activated blast cells expressed a smaller number of cell surface IL-2 receptor since IL-2 adsorption to the patient cells was lower than that to the normal cells (P less than 0.01). On the other hand, IL-1 production by LpS-stimulated adherent-PBMC from the patients was in agreement with that from the normal controls (P greater than 0.05). From above results, it seems that human organism following infection of Schistosoma japonicum might display a sort of suppressive phenomenon in the production of and the response to IL-2. PMID- 1908358 TI - [Preliminary study of naturally occurring anti-idiotypic antibodies in schistosomiasis japonica]. AB - In this study, naturally occurring anti-idiotypic antibodies in sera from patients with schistosomiasis japonica were demonstrated by using McAb (5B5H) ELISA. McAb 5B5H against Schistosoma japonicum soluble egg antigen (SEA) was purified by precipitation with 50%, 40% and 33% saturated (NH4)2SO4 and coupled to CNBr-activated Sepharose 4B (Pharmacia). 5B5H column was loaded with sera from two patients with schistosomiasis japonica and then the bound material was eluated with 3M KCNS. The resulting eluate was further characterized with McAb ELISA and complement fixation test in order to minimize the possible interference of circulating antigen-antibody complex. The results showed that the eluate contained mainly anti-Id antibodies. In the competitive 5B5H-ELISA tests, SEA markedly inhibited the interaction of 5B5H (Id) and anti-Id anti-bodies, suggesting that the relevant idiotype is within or adjacent closely to antigen binding site of anti-SEA molecule. The anti-Id antibodies were detected using 5B5H-ELISA in patients with schistosomiasis japonica from A and B areas, positive rate of 35.1% (13/37) and 60% (18/30) was obtained respectively. No cross or false reactions were found with sera from patients with fasciolopsiasis buski (0/15), clonorchiasis sinensis (0/15) and normal group of students (0/54) with the exception of one out of 20 patients with paragonimiasis westermani. PMID- 1908359 TI - Glomerular filtration rate: a comparison between Cr-EDTA clearance and a single sample technique with a non-ionic contrast agent. AB - An algorithm for the calculation of the glomerular filtration rate (GFR) from a single-point determination of the serum concentration of the non-ionic contrast medium iohexol has been evaluated. The algorithm is based upon the assumption that the distribution volumes of iohexol and 51Cr-EDTA are similar. It includes correction factors for non-immediate mixing and irregular extracellular distribution during the elimination phase. The calculated GFR from single-point determinations of iohexol obtained at 180, 200, 220 and 240 min after injection of 5 mL of this compound (300 g iodine/L) were compared with the results from simultaneously performed 51Cr-EDTA clearance in 98 patients. The single-point iohexol clearance values calculated from the different sampling times showed a coefficient of correlation of more than 0.95 to 51Cr-EDTA clearance. PMID- 1908360 TI - Immunoglobulin A subclass distribution in serum from patients with the acquired immunodeficiency syndrome. AB - Immunoglobulin levels are elevated in the acquired immune deficiency syndrome (AIDS) and one class, IgA, has been suggested as a marker of disease progression. IgA is composed of two subclasses, IgA1 and IgA2; circulating IgA1 is roughly 85% of the total in healthy individuals. We have attempted to determine if the subclass distribution in the serum of AIDS patients is similar to that of healthy subjects. IgA subclasses were measured by end-point radial immunodiffusion (RID). Sera from 27 AIDS patients and 27 controls who approximated the age and sex composition of the AIDS group were studied. Total IgA by RID, i.e., the sum of IgA1 and IgA2, correlated well with IgA determined by rate nephelometry (n = 51; r = 0.918; p less than 0.0001). Total IgA (IgAT), IgA1 and IgA2 were significantly elevated in the AIDS group (p less than 0.0001, p = 0.0001 and p = 0.033, respectively). However, the AIDS patients had a roughly equivalent percent IgA1 of total (87.2 +/- 7.6%) as the control group (85.0 +/- 6.1%). The subclass distribution is not altered in AIDS patients, and serum concentrations of IgA subclasses do not reflect possible alterations in secretory IgA which might be expected because of recurrent mucosal infections in these patients; nor is the subclass distribution altered due to clearance of predominantly IgA1-bearing immune complexes. PMID- 1908361 TI - Light chain ratios of serum immunoglobulins in disease. AB - We have determined the individual kappa (kappa)/lambda (lambda) ratios of serum IgG, IgA, and IgM in normal subjects and patients with rheumatoid arthritis, systemic lupus erythematosus, hepatic cirrhosis and IgA nephropathy--40 in each group. Serum samples were first screened by agarose electrophoresis to exclude paraproteinaemia. Concentrations of IgG, IgA, and IgM were determined by enzyme linked immunosorbent assay (ELISA). The kappa and lambda chain concentrations of each immunoglobulin class were assayed by an ELISA method first developed by us for the determination of kappa/lambda ratios. Our results showed that kappa/lambda ratios of serum IgA and IgM were significantly different from that of IgG in normal subjects and the 4 groups of patients studied (p less than 0.01). The kappa/lambda ratios of individual immunoglobulins in patients with rheumatoid arthritis, systemic lupus erythematosus and liver cirrhosis were similar to those of normal subjects. However, patients with IgA nephropathy displayed a distinctly lower IgA kappa/lambda ratio, suggesting a unique antibody response in the immunopathogenesis of this disease. PMID- 1908362 TI - Quantitation of serum apolipoprotein A-I, A-II, B, C-II, C-III and E in healthy Japanese by turbidimetric immunoassay: reference values, and age- and sex-related differences. AB - Serum apolipoproteins (Apo) A-I, A-II, B, C-II, C-III and E were determined in healthy Japanese subjects (male 1,603, female 1,800, aged 4-95 yr) by the turbidimetric immunoassay, with six kinds of automated instruments, and the commercial reagent kits with standards. There was a high degree of interlaboratory comparability of analytical values among the 15 participating laboratories. The reference values were calculated for adult males and females (male 677, female 467, aged 21-60 yr). Apo A-I and E levels were significantly higher and Apo C-II and C-III were significantly lower in females than in males. Furthermore, serum Apo A-I and A-II tended to decrease, and Apo B to increase with age. Apo C-II, C-III and E tended to decrease after 60 yr of age. PMID- 1908363 TI - N-acetyl-beta-D-glucosaminidase (NAG) isoenzymes release from human monocyte derived macrophages in response to zymosan and human recombinant interferon gamma. AB - Secretion of N-acetyl-beta-D-glucosaminidase (NAG) isoenzymes by human blood monocyte-derived macrophages in response to zymosan and human recombinant interferon-gamma was studied. Macrophages were found to release NAG in response to zymosan, but interferon-gamma has no effect on secretion. Isoenzyme separation by isoelectric focusing demonstrates that non stimulated and zymosan or interferon-gamma treated macrophages release predominantly NAG B and, to a lesser extent, NAG A isoenzymes. In all these conditions, the intracellular intermediate form NAG I could not be detected in the media. Thus, activated macrophages may not be the source of NAG intermediate forms I and P in pathological or maternal serum. In contrast, macrophages could contribute to a significant elevation of urinary activity and NAG B excretion in response to inflammatory conditions. PMID- 1908364 TI - Effects of calcium on light-activated GTP-binding proteins in squid photoreceptor membranes. AB - 1. At least two distinct G-proteins are activated by light in squid photoreceptor membranes, a 45,000 mol. wt cholera toxin substrate and a 40,000 mol. wt pertussis toxin substrate. 2. The light-stimulated GTPase activity is partially inhibited by pretreatment with either toxin and abolished by treatment with both toxins. 3. At 24 degrees C, a free calcium ion concentration of 1 microM inhibits GTPase activity of both toxin substrates and ADP ribosylation by pertussis toxin. 4. This calcium sensitivity of squid G-proteins may be important in interpretation of experimental results on the phosphoinositide or other signalling pathways in squid visual transduction. PMID- 1908365 TI - Dolichol levels during development and ageing of Drosophila melanogaster. AB - 1. Dolichol levels in the fruit fly, Drosophila melanogaster were determined at the larva and pupa stages and in 1, 10, 20 and 30-day-old flies. 2. Free dolichol increased from 1.2 micrograms/g wet weight in the larvae to 14.9 micrograms/g in 30-day-old flies, while total dolichol increased from 3.4 micrograms/g in the larvae to 21.2 micrograms/g at 30-days-old. 3. Dolichol released after saponification is primarily from dolichyl fatty acid ester, which accounts for up to 65% of the total dolichol. 4. The major dolichol homologs, which remain relatively constant throughout development and ageing in D. melanogaster, are C 80, C-85 and C-90, which represent approximately 7%, 60% and 33%, respectively. PMID- 1908366 TI - Comparison of bovine, sheep and goat milk lactoferrins in their electrophoretic behavior, conformation, immunochemical properties and lectin reactivity. AB - 1. The biochemical properties of bovine, goat and sheep lactoferrin were compared. Molecular weights of the three lactoferrins were estimated to be 78,000 to 80,000 as determined by SDS-PAGE. By IEF, microheterogeneity was observed for all of them. 2. Partial antigenic identity was observed between bovine lactoferrin and goat or sheep lactoferrin by immunodiffusion method. 3. CD spectra at the u.v. region of the three lactoferrins suggested their similar secondary and tertiary structural profiles. 4. Reactivities with peroxidase conjugated lectins showed that the carbohydrate compositions of the three ruminants' lactoferrin were the same but not identical with that of human lactoferrin. PMID- 1908367 TI - Remarks on reliability of rectal biopsy in the assessment of cure following treatment of schistosomiasis japonica. PMID- 1908368 TI - Studies on small intestinal mucosal morphology lactase activity and lactose hydrolysis rate in childhood with diarrhea. AB - Small intestinal mucosal morphology, lactase activity and lactose hydrolysis were examined by peroral intestinal biopsy and intraluminal perfusion of the small intestine in 28 patients with acute and chronic diarrhea. This study shows that lactase deficiency and mucosal damage are more common in childhood diarrhea, and there are positive correlations among intestinal morphology, lactase activity and lactose hydrolysis. A small bowel biopsy is useful both in establishing the diagnosis and guiding dietary treatment for infants with chronic diarrhea. The pathophysiologic mechanism of diarrhea is also discussed. PMID- 1908369 TI - Regulation of the pituitary gonadotrope by gonadotropin-releasing hormone: multiple intracellular effectors. AB - Gonadotropin-releasing hormone (GnRH) stimulates synthesis and release of the pituitary gonadotropins luteinizing hormone (LH) and follicle stimulating hormone (FSH). Other actions of GnRH include gonadotrope sensitization and desensitization as well as stimulation of GnRH receptor synthesis. Gonadotropin release initiated by increased intracellular calcium is a result of calcium mobilization from intracellular stores and influx of extracellular calcium through receptor-operated channels. Increases in intracellular calcium and the presence of both calmodulin and calmodulin binding-proteins in pituitary suggests that formation of Ca(2+)-calmodulin complexes and subsequent alteration of calmodulin-binding protein activity are likely important intermediate steps in the signaling pathway of LH release. Although activation of protein kinase C is not necessary for GnRH-stimulated LH release or gonadotrope desensitization, it appears to be essential for GnRH effects on LH beta gene expression. Therefore gonadotrope responses are apparently mediated by multiple intracellular signaling mechanisms. PMID- 1908370 TI - [2-Pfeiler acetabulum fracture with central hip dislocation and ipsilateral femoral neck fracture in epileptic seizure]. PMID- 1908371 TI - [The kinetics of plasma coagulation fibrinolysis levels in acute myocardial infarction before and after treatment with intravenous urokinase]. AB - The levels of tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor (PAI) and other substances of coagulation-fibrinolysis, such as fibronectin (Fn) and von willebrand factor (vWF) as well as the activity content of antithrombin-III(AT-III) in plasma were determined in 20 patients with acute myocardial infarction (AMI). In 11 of them these measurements were carried out before and after the treatment with urokinase (UK1000 000 IU). The results suggested that the function of coagulation-fibrinolytic system was disturbed in AMI. Thrombolytic treatment with UK could interfere and improve the stabilization of fibrinolytic activity in the body, but these actions last only short time. Some substances of coagulation showed change with UK treatment. PMID- 1908372 TI - [A multiclinic double-blind, comparative clinical trial on misoprostol in the treatment of duodenal ulcer]. AB - A clinical trial of misoprostol, an analog of PGE1 produced by G.D. Searle & Co., on treatment of duodenal ulcer was carried out in five hospitals in Beijing, Shanghai, and Guangzhou. Totally 94 cases were treated with misoprostol 200 micrograms q.i.d. for 4 weeks. A parallel comparison was made, using cimetidine 200 mg q.i.d. A double-blind, double-dummy study was conducted. The result showed that the therapeutic efficacy of misoprostol in duodenal ulcer is similar to that of cimetidine. The ulcer healing rate in four weeks being 60.7% and 67.9% respectively, while the overall effectiveness rate being 77.7% and 80.2%. There was no statistically significant difference between the two medication groups. The side effect of misoprostol is mainly mild diarrhea (6.4%), but it disappears despite the continued use of medication. To our impression, misoprostol represents a new therapeutic approach for treatment of peptic ulcer in addition to acid controlling H2 blockers. PMID- 1908373 TI - [The effect of intravenous alimentation on protein synthesis after major operation]. AB - The whole body protein was found to decline by 16.4% in patients after radical gastrectomy without IVN support, and the levels of visceral proteins, such as serum albumin, C-reactant and fibronectin, also obviously decreased. If IVN support was given after operation, the whole body protein synthesis was 57.7% higher than that in the controlled group. The blood levels of visceral proteins were also elevated, with a significant difference in the fibronectin concentration in IVN group as compared with either preoperative or controlled value. PMID- 1908374 TI - [Surgical treatment of traumatic epilepsy]. AB - Fifteen patients with traumatic epilepsy were treated surgically. Cortico electroencephalography was used during the operation. Meningo-encephalo cicatrix was found in 8 patients, scar formation in brain parenchyma in 4, meningoencephalocele in 2, and porencephalia in 1. Seven of the 15 patients were examined by CT, showing more accurate localization of pathological changes. Seizure subsided in 8 patients. Anti-epileptic drugs were still used in 4 patients, but the frequency and severity of epileptic attack were obviously decreased. There was no operative mortality. The indications, techniques of the operation and the postoperative management were discussed. PMID- 1908375 TI - Regulation of rat hypothalamic preprogrowth hormone-releasing factor messenger ribonucleic acid by dietary protein. AB - To further evaluate nutrient regulation of GRF synthesis, we measured hypothalamic preproGRF messenger (m) RNA in food-deprived rats refed diets varying in nutrient composition by nuclease protection analysis. Adult male Sprague-Dawley rats were allowed free access to food (Fed), food deprived for 72 h (72-h FD), or 72 h FD then refed for 72 h with either a normal (NF) diet or isocaloric diets containing no protein (PF), carbohydrate (CF), or fat (FF). Seventy-two-hour FD rats displayed the expected 80% reduction in hypothalamic preproGRF mRNA. Upon refeeding, levels were normalized in rats refed NF, CF, or FF diets. In contrast, preproGRF mRNA in rats refed a PF diet was similar to that in 72-h FD rats. Rats refed a PF diet failed to gain weight and consumed less food than animals refed NF, CF, or FF diets. However, the lack of the GRF response to the PF diet was due to protein deprivation rather than caloric restriction, since hypothalamic preproGRF mRNA returned to 66% of Fed values in rats refed an equivalent amount (grams per day) of a NF diet. In 72-h FD rats refed isocaloric diets containing 4%, 8%, or 12% protein, preproGRF mRNA was restored to Fed values in a protein concentration-dependent manner being completely restored by the 12% diet. A lack of dietary protein was sufficient to regulate hypothalamic preproGRF mRNA since feeding rats a PF diet without prior food deprivation resulted in 70% reduction in preproGRF mRNA, whereas CF and FF diets were without effect. These data indicate that decreased hypothalamic preproGRF mRNA expression in 72-h FD rats occurs as a result of dietary protein deprivation. PMID- 1908376 TI - Control of gonadotropin secretion in the ovine fetus. III. Effect of castration on serum follicle-stimulating hormone levels during the last trimester of gestation. AB - Gonadal involvement in fetal FSH regulation was examined by studying FSH levels in 13 female (7 castrate and 6 sham control) and 13 male (8 castrate and 5 sham control) chronically catheterized ovine fetuses operated upon in utero at 106-115 days gestation (term = 147 days). These fetuses had been studied previously for pulsatile LH secretion every 2-7 days over a 2- to 38-day period until fetal delivery or death. From each study day, 3 1-h spaced blood samples (1.5-2.0 ml) were taken for FSH determination by RIA (NIH FSH-S8 standard), and the results were averaged. The overall mean was then calculated for each fetus. In female fetuses, there was no significant difference in mean serum FSH levels between castrates [53.4 +/- 5.0 ng/ml (+/- SEM)] and controls (52.5 +/- 14.4 ng/ml). In contrast, serum FSH levels in the eugonadal males were significantly (P less than 0.001) lower (23.4 +/- 8.0 ng/ml) than those in castrate males (56.9 +/- 7.1 ng/ml, a value comparable to those observed in both female groups). Mean serum FSH levels declined significantly (P less than 0.001) in castrate fetuses of both sexes after 125 days (61.5 +/- 5.6 vs. 42.4 +/- 7.7 ng/ml in females; 64.1 +/- 6.1 vs. 51.5 +/- 8.6 ng/ml in males). In the males, the FSH decline did not reach sham control levels, which remained unchanged with advancing gestation. Moreover, mean serum FSH levels were significantly higher in a group of 4 male fetuses (62.2 +/- 13.7 ng/ml) castrated at 121-130 days gestation compared to values in 3 age-matched sham castrate controls (22.1 +/- 2.6 ng/ml; P less than 0.001). The increment in serum FSH levels in castrate compared to sham castrate male fetuses demonstrates an important role for the fetal testis in FSH regulation from 106 days gestation until term. The lack of a detectable castration effect on the relatively high serum FSH levels in eugonadal females indicates that the fetal ovary does not play a similar role and suggests that in females, FSH is secreted in a functionally castrate mode. The decline in FSH levels after 125 days in castrate fetuses of both sexes may result at least in part from the previously reported coincident rise in circulating levels of feto-placental sex steroids and/or PRL.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1908377 TI - Regulation of transepithelial electrical resistance in two-compartment Sertoli cell cultures: in vitro model of the blood-testis barrier. AB - The effects of FSH, testosterone (T), and incubation temperature on the development of inter-Sertoli cell (Sc) tight junctions were investigated in vitro by using repetitive measurements of transepithelial electrical resistance (TER). Control cultures developed stable TER of 100-145 omega cm2 during the initial 3-4 days of incubation at either 33 or 36.5 C, suggesting the formation of simple but continuous tight junctions. The presence of FSH (200 ng/ml) at 33 C delayed the onset of TER development by 3-5 days. The addition of FSH at the time of stable TER (day 5) resulted in a rapid (24 h) decrease of TER to 35-40 omega cm2, which returned to the control level during the subsequent 5-7 days. T alone (0.001-10 microM) caused an early and dose-dependent increase in TER to 165-240 omega cm2. In mono-layers incubated at 36.5 C, the continuous presence of FSH resulted in a dose-dependent increase in TER, which stabilized at 260-380 omega cm2 after 4-6 days. At this temperature, the addition of FSH on day 5 caused a rapid drop of TER similar to that observed at 33 C. This drop could not be prevented by antiproteases (aprotinin, epsilon-aminocaproic acid, or 10% fetal bovine serum) and was followed by an increase in TER up to 260-300-omega cm2. The Sc monolayers developed FSH-induced TER of 230-280 omega cm2 at 33 C, but only after several days of culture at 36.5 C. The effects of T at 36.5 and 33 C were similar, but the maximal TER values were significantly higher (290-380 omega cm2) at 36.5 C. The concomitant presence of T and FSH at 36.5 C resulted in the highest TER levels (580-1200 omega cm2) within 4-6 days, suggesting the synergistic effect of the two hormones on TER development. Dihydrotestosterone was more effective than T when used together with FSH, whereas estradiol had no effect. The different patterns of TER did not result from differences in Sc number or metabolic activity and probably reflected developmental and/or maturational changes in the inter-Sc tight junctions. It is concluded that FSH, T, and temperature play a role in the development of high TER by Sc monolayers (formation of tight junctions) in vitro. FSH and T appear to regulate TER via separate pathways and to cooperate by a yet unknown synergistic mechanism.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1908378 TI - Efficacy of adrenaline, lignocaine-adrenaline and isoprenaline as a test dose in halothane-anaesthetized lambs. AB - It has been shown that an epidural test dose with adrenaline does not always detect an intravascular injection in halothane-anaesthetized children. To ascertain whether test dosing with other agents might be more useful, we sought to determine if and at what dose levels three different intravenous drugs (adrenaline, isoprenaline and 1% lignocaine with 1/200,000 adrenaline) produced an increase in heart rate (HR) in halothane-anaesthetized lambs. Eight 2-week-old lambs were anaesthetized with 1% halothane in oxygen. The lambs were intubated and ventilated in order to maintain end-tidal and arterial CO2 within normal limits; HR and blood pressure before and 15-180 s after the injection of four increasing doses of each drug were recorded. The same set of measurements was repeated after the intravenous injection of atropine 10 micrograms kg-1. Adrenaline-containing doses produced a more sustained increase in HR (P less than 0.05, ANOVA) at lower doses of adrenaline when atropine was injected first. This increase did not occur in all lambs, and dysrhythmias were manifest in some. Isoprenaline always produced a significant increase in HR without dysrhythmias whether atropine was given or not. We conclude that in halothane-anaesthetized lambs, isoprenaline is a more reliable indicator of intravascular injection than adrenaline. PMID- 1908379 TI - Meningococcal chest infections in a general hospital. AB - In the course of one calendar year (1989-1990), 46 specimens of respiratory secretions (from 44 patients) cultured in the microbiology department of a large district general hospital in The Netherlands were found to yield Neisseria meningitidis. Twenty-eight of the 46 samples yielded pure cultures of meningococci and 18 yielded other recognised respiratory pathogens as well. Only one patient had pneumonia, whereas 19 had acute respiratory infections and 18 acute purulent exacerbations of chronic bronchitis. The remaining patients, who had a variety of symptoms, all had purulent sputum. Only 8 of the 44 patients were under 40 years of age; 21 were aged more than 60 years. Serological grouping and subtyping showed a predominance of group B strains (in 24 of 44 patients) and 13 strains were non-groupable. The importance of recognising or overlooking meningococci in cultures of respiratory secretions is discussed. PMID- 1908380 TI - Characterization of Neisseria meningitidis serogroup A strains from an outbreak in France by serotype, serosubtype, multilocus enzyme genotype and outer membrane protein pattern. AB - In an attempt to determine the epidemiological relationship between cases of infection caused by Neisseria meningitidis serogroup A in France between August 1987 and December 1988, and an outbreak which occurred in Mecca in August 1987, markers such as serotype, serosubtype, multilocus enzyme genotype and outer membrane protein (OMP) pattern were used to characterize the bacterial isolates. From a total of 28 cases, 20 strains were isolated. Sixteen isolates, including one which undoubtedly originated from the Mecca epidemic, were homogenous (serotype 4, serosubtype P1.9, multilocus enzyme genotype of clone III-1, identical OMP pattern). Four isolates had a different OMP pattern with little or no P1 protein, no P4 and no P6. Two of these isolates belonged to other clones (I.1 and group I) and they were considered to be unrelated to the Mecca epidemic strains. The origin of the remaining two isolates was not clear. It is concluded that the majority of the Neisseria meningitidis serogroup A strains recently isolated in France originate from the Mecca epidemic. PMID- 1908381 TI - Activity of some antiseptics against urinary tract pathogens growing as biofilms on silicone surfaces. AB - The activity of chlorhexidine, mandelic acid and a mandelic/lactic mixture were tested against biofilms of four species of gram-negative nosocomial organisms that commonly infect the catheterized urinary tract. Cells growing on silicone discs were exposed to concentrations of agents used in bladder instillation. Citrobacter diversus biofilms proved to be sensitive to all three agents. Pseudomonas aeruginosa, Proteus mirabilis and Klebsiella pneumoniae all survived well in chlorhexidine but their viability was significantly reduced by the mandelic acid formulations. These results suggest that bladder instillations of mandelic acid or mandelic/lactic acids would be more effective than chlorhexidine in eliminating biofilms from catheter surfaces. PMID- 1908383 TI - Rapid diagnosis of tuberculous meningitis with a dot enzyme immunoassay to detect antibody in cerebrospinal fluid. AB - A simple dot enzyme immunoassay (Dot-EIA) was carried out to detect antibody to Mycobacterium tuberculosis antigen 5 in cerebrospinal fluid (CSF) specimens from 40 patients with a clinical diagnosis of tuberculous meningitis (TBM). The assay gave a positive reaction in all ten patients with culture proven TBM. In 30 culture negative patients with TBM, the assay was positive at a titre of 1:16 in 18 patients. In 40 patients with non-tuberculous neurological diseases (control group) the assay was negative at a titre of 1:16. The Dot-EIA had an overall sensitivity of 70% and a specificity of 100% in the diagnosis of TBM. This assay could be used as a rapid screening test to establish the diagnosis of TBM, particularly in patients in whom bacteriological investigations for Mycobacterium tuberculosis in CSF specimens are negative. PMID- 1908382 TI - Activity of antiseptics against biofilms of mixed bacterial species growing on silicone surfaces. AB - As part of a programme to establish the relative merits of antiseptics that are used as bladder instillations to control urinary tract infections in patients with indwelling catheters, the activity of five such formulations were tested against dense (10(9) cfu/cm2) mixed biofilms composed of Citrobacter diversus, Pseudomonas aeruginosa and Enterococcus faecalis growing on silicone discs. All three species were resistant to chlorhexidine (200 mg/l) and povidone-iodine (1% v/v) in the biofilm mode of growth, whereas these agents rapidly eliminated viable cells from urine suspensions of the mixed community. Lactic acid (1% v/v) produced a 1 log reduction of the biofilm population within 30 min of exposure. The mandelic acid (1% w/v) and mandelic acid (0.5% w/v)/lactic acid (0.5% v/v) mixture proved to be the most effective in eliminating the biofilm organisms. It is suggested that these latter solutions should now be tested for efficacy in bladder washouts against urinary tract infections in catheterized patients. PMID- 1908385 TI - A comparison of buccal nitroglycerin and sublingual nitroglycerin in the prophylaxis and treatment of exertional (situation-provoked) angina pectoris. AB - Suscard is a buccally administered formulation which provides rapid introduction of nitroglycerin directly into the systemic circulation and, by virtue of its sustained-release properties, may confer protection against anginal attacks for several hours. Its efficacy has been established in angina pectoris and more recently its usefulness has been extended to include the management of unstable angina and acute heart failure. Buccal nitroglycerin combines the possibilities of short-term treatment and more extended prophylaxis. In a multicentre double blind study the efficacy of buccal nitroglycerin and sublingual nitroglycerin were compared in patients with proven chronic stable exercise-induced angina as regards anginal attacks and capacity for physical activity. The conclusion is that the two formulations of nitroglycerin have a comparable effect in the treatment of acute attacks of angina pectoris. Buccal nitroglycerin has many advantages when used prophylactically. This is documented by less frequent anginal attacks and a more prolonged duration of effect resulting in an increased physical activity. PMID- 1908384 TI - One-year follow-up after recombinant tissue plasminogen activator administered to patients with acute myocardial infarction. AB - Of 106 patients seen within 4 h of chest pain with 107 episodes of acute myocardial infarction, nine died before or during hospitalization mainly from cardiogenic shock, and four died during the next year, three were sudden deaths. The 93 survivors were reviewed at a mean of 53 (range 49-70) weeks after infarction. Of these 93, 18 had had attempted angioplasty (successful in 12) and 15 had had coronary artery bypass grafting (including one patient who had coronary artery bypass grafting performed after unsuccessful angioplasty). The remaining 61 patients continued on medical therapy only. During the one-year follow-up two patients suffered reinfarction and a further 22 had one or more cardiac admissions, mostly for chest pain. At review, 22 patients had angina (16 New York Heart Association Grade I or II) and five dyspnoea (all NYHA Grade II). Forty-three patients were taking oral nitrates, 53 were receiving calcium antagonists, 54 were using betablocking agents and 73 used anti-platelet agents. However, many of these patients continued on anti-anginal therapy prophylactically after their myocardial infarction, without continuing chest pain. Thus after recombinant tissue plasminogen activator therapy and following hospital discharge the mortality rate for patients with acute myocardial infarction was four out of 97 (4.1%) and reinfarction rate among survivors was two out of 93 (2.2%). Although the incidence of cardiac symptoms was low this may be partly due to the high incidence of angioplasty and coronary artery grafting, together with the use of anti-anginal agents. PMID- 1908386 TI - BAY P 1455, a thiazolylaminobenzimidazole derivative with gastroprotective properties in the rat. AB - The antiulcer activity of BAY P 14551 a thiazolylaminobenzimidazole derivative, was evaluated in different experimental ulcer models and its antiulcer activity was compared to that of different reference drugs. The overall activity of the compound was equal to or more potent than that of reference antiulcer drugs, such as pirenzepine, cimetidine and carbenoxolone, but it was not as potent as rioprostil. The ED50 values (expressed as mumol/kg p.o.) were 68 (confidence limits: 51-91) for indomethacin-induced ulcers, 21 (confidence limits: 13-31) for stress-induced ulcers and 1260 mumol/kg p.o. (confidence limits: 412-3800) for ulcers induced by absolute ethanol. The compound had no activity against cysteamine-induced duodenal ulcers and lost its cytoprotective activity in adrenalectomised rats. Since inhibition of gastric acid secretion was seen, if at all, only with the higher doses, the gastro-protective action of BAY P 1455 seemed not to be due to an antisecretory effect, but more likely to a gastroprotective action as hypothesised for prostaglandins. PMID- 1908387 TI - Central administration of ibuprofen failed to block the anorexia induced by interleukin-1. AB - Interleukins are synthesized by inflammatory cells and are thought to be involved in the anorexia associated with severe infection. In the present study, the possible involvement of prostaglandins in the anorexia caused by interleukin-1 was investigated. Recombinant human interleukin-1 beta (IL-1 beta). 17 ng/rat, injected into the third cerebroventricles significantly suppressed food intake and reduced the body weight gain in rats deprived of food for 18 h. Central administration of ibuprofen (IBP, 5-500 microgram/rat), a selective cyclooxygenase blocker, failed to attenuate the feeding suppression and body weight loss induced by IL-1 beta injection, although central administration of 50 microgram IBP blocked the increase of body temperature caused by central IL-1 beta. The data obtained suggest that a peripheral prostaglandin synthesizing system may play an important role in the anorexia caused by IL-1 beta. PMID- 1908388 TI - Inhibition by thyrotropin-releasing hormone of epileptic seizures in spontaneously epileptic rats. AB - The effects of thyrotropin-releasing hormone (TRH) were investigated on absence like seizures, which are characterized by the sudden appearance of 5-7 Hz spike wave-like complexes in the cortical and hippocampal EEG, and on tonic convulsions of spontaneously epileptic rats (SER; zi/zi, tm/tm), a double mutant obtained by mating zitter homozygote (zi/zi) with tremor heterozygote rats (tm/+). TRH (5 and 10 mg/kg i.v.) inhibited the appearance of both absence-like seizures and tonic convulsions of SER without inducing obvious changes in the background EEG. The inhibitory effects were seen 5-20 min after injection of 10 mg/kg TRH and were antagonized by pretreatment with haloperidol (0.5 and 1.0/kg i.p.), although haloperidol alone did not affect the seizures. These results suggest that TRH has an antiepileptic effect in the genetically defined animal model, SER, and that the effect is mediated by the central dopaminergic system. PMID- 1908389 TI - Effect of chronic ritanserin or clorgyline on amine and metabolite levels in rat frontal cortex. AB - As part of an investigation of ritanserin-induced receptor down-regulation, monoamine and metabolite levels in rat frontal cortex were measured following chronic ritanserin (2 mg/kg per day) or clorgyline (10 mg/kg per day) administration. Clorgyline increased 5-hydroxytryptamine (5-HT) by 83%, noradrenaline (NA) by 54%, and dopamine (DA) by 16% and decreased 5 hydroxyindoleacetic acid (5-HIAA) by 28%, homovanillic acid (HVA) by 57% and 3,4 dihydroxyphenylacetic acid (DOPAC) by 67%. All these changes were statistically significant (P less than 0.001) except for the increase in DA. Ritanserin increased 5-HT by 30%, NA by 33% and DA by 26% and decreased 5-HIAA by 22%, HVA by 23% and DOPAC by 40%; however, only the increases in 5-HT and NA reached statistical significance (P less than 0.05). Monoamine oxidase (MAO) activity in cortical homogenates was also measured following the chronic ritanserin and clorgyline regimens and also following ritanserin administration in vitro. Chronic clorgyline and ritanserin inhibited MAO activity by 60 and 39%, respectively. In vitro, ritanserin administration at concentrations of less than 10(-6) M had no effect on MAO activity but at doses higher than 10(-6) M, MAO activity was inhibited in a dose-dependent manner from 18 +/- 0.5% at 3 x 10(-6) M to 63 +/- 9% at 10(-4) M. Thus, ritanserin appears to act as an MAO inhibitor in addition to being a 5-HT2 antagonist and this may be related to its ability to induce 5-HT2 receptor down-regulation. PMID- 1908390 TI - Sarcoma-180 cells and human colorectal tumor cells under in vitro hypoxic conditions are more sensitive to mitomycin C and carboquone. AB - The effects of oxygen concentration on the chemosensitivity of mouse sarcoma-180 (S-180) cells and human colorectal cancer tissues to mitomycin C (MMC) or carboquone (CQ) were determined in vitro, since evidence had been obtained that these drugs are more effective in HeLa cells. The results were as follows: (a) S 180 cells exposed to various concentrations of MMC or CQ for 2 h under conditions of normal aeration (about 20%) or hypoxia (5.0% and 0%) were then maintained under normal conditions of aeration for 3 days. Change of viability was assessed by succinate dehydrogenase (SD) activity. With exposure of the cells to MMC or CQ, under anoxic conditions (O2:0%), SD activity decreased to a greater extent than seen in the control cells. The value for CQ was from 61.5% to about 36.2%. (b) The decrease in the SD activity of 20 colorectal cancer tissues kept under conditions of anoxia was compared with findings under normally aerated conditions, following exposure to 30 microM of MMC or 1.6 microM of CQ. On exposure to MMC or CQ under anoxic conditions, SD activity decreased significantly, compared with normally aerated conditions (P less than 0.001 for MMC; P less than 0.05 for CQ). As colorectal cancer is less sensitive than other tissues to various chemotherapeutic agents, we recommend that MMC and CQ be prescribed to treat patients with these malignant lesions. PMID- 1908391 TI - Topics in parenteral nutrition for the 1990s. AB - Research and development in parenteral nutrition delivery systems, infection control, and new therapeutic agents promise to optimize the use of parenteral nutrition for the 1990s. Nurses must integrate these new technologies into patient care and apply research findings to clinical practice. Critical care nurses are at the forefront of these changes because of their unique position as expert clinicians at the bedside of the patients most in need of nutritional interventions. PMID- 1908392 TI - Combined radioprotection by preirradiation peroral cystamine and postirradiation glucan administration. AB - The possibilities of combined radioprotection, using preirradiation peroral cystamine and postirradiation intraperitoneal glucan administration in sublethally and lethally whole-body gamma-irradiated mice were investigated. The results demonstrated at least additive radioprotective effects of both agents, manifested in the enhancement of postirradiation haemopoietic recovery and increased survival of irradiated mice. The effects appear to depend on the sequential cell protection mediated by cystamine and enhanced haemopoietic repopulation induced by glucan. PMID- 1908393 TI - Intracellular ratio between monovalent cations (Na+/K+), and transcriptional activity of genes in tumour cells. AB - The effects of the intracellular Na+/K+ ratio on transcriptional activity of ribosomal, c-fos, beta-actin and histone genes of Ehrlich ascites tumour cells and P-388 leukaemia cells have been investigated. Optimum values of the Na+/K+ ratio for selective transcription of genes are shown, they are in accordance with the Na+/K+ ratio and mRNA content of respective genes during the cell cycle. Differential activation and repression of these genes do not correlate with the total synthesis rate of RNA during the cell cycle. The data indicate a selective nature of the action of monovalent cations on gene expression during the cell growth. PMID- 1908394 TI - [Changes of immunosorption properties in the blood and its components at various times after UV-irradiation]. AB - Immunosorption activity in reference to antirhesus antibodies, of UV-irradiated Rh-positive preserved blood as well as of red blood cell pack and leucocytic thrombocytic suspension prepared from this blood, was studied in varying terms after irradiation. The whole blood and red blood cell pack immunosorption activity significantly increased immediately after irradiation. The effect lasted during two days. The sorption capacity of leucocytic-thrombocytic suspension remained unchanged immediately after irradiation, and two days later it was almost lost. PMID- 1908395 TI - Amphibian prolactins: activity in the eft skin transepithelial potential bioassay. AB - The effects of purified prolactins isolated from frogs (fPRL; Rana catesbeiana) and newts (nPRL; Cynops pyrrhogaster) were compared with those of ovine prolactin (oPRL) and thyrotropin releasing hormone (TRH) in the eft (Notophthalmus viridescens) skin transepithelial potential (TEP) bioassay. At total doses as low as 0.4 micrograms/animal, both fPRL and nPRL were as effective as oPRL in reducing eft skin TEP. By contrast, TRH at total doses as high as 400 micrograms/animal was ineffective in altering eft skin TEP. These data provide the first direct evidence that amphibian PRLs can exert significant physiological control over salamandrid integumental sodium transport. PMID- 1908396 TI - Purification and characterization of a cell wall hydrolase encoded by the cwlA gene of Bacillus subtilis. AB - A cell wall hydrolase of Bacillus subtilis was prepared from Escherichia coli cells harboring a plasmid containing the B. subtilis cwlA gene and purified by hydroxyapatite column chromatography and HPLC through TSK-gel G3000SWXL. In contrast to the molecular mass of 29,919 Da deduced from its nucleotide sequence, the purified CWLA is a 23 kDa protein. Characterization of the specific substrate bond cleaved by CWLA indicated the enzyme is an N-acetylmuramyl-L-alanine amidase. A 32-kDa precursor protein was detected on zymography of a crude cell homogenate. Some of the enzymatic properties of CWLA are also described. PMID- 1908397 TI - Mutational analysis of the Drosophila miniature-dusky (m-dy) locus: effects on cell size and circadian rhythms. AB - A mutational analysis has been performed to explore the function of the Drosophila melanogaster miniature-dusky (m-dy) locus. Mutations at this locus affect wing development, fertility and behavior. The genetic characterization of 13 different mutations suggests that m and dy variants are alleles of a single complex gene. All of these mutations alter wing size, apparently by reducing the volume of individual epidermal cells of the developing wing. In m mutants, epidermal cell boundaries persist in the mature wing, whereas they normally degenerate 1-2 hr after eclosion in wild-type or dy flies. This has permitted the direct visualization of cell size differences among several m mutants. Mutations at the m-dy locus also affect behavioral processes. Three out of nine dy alleles (dyn1, dyn3 and dyn4) lengthen the circadian period of the activity and eclosion rhythms by approximately 1.5 hr. In contrast, m mutants have normal circadian periods, but an abnormally large percentage of individuals express aperiodic bouts of activity. These behavior genetic studies also indicate that an existing "rhythm" mutation known as Andante is an allele of the m-dy locus. The differential effects of certain m-dy mutations on wing and behavioral phenotypes suggest that separable domains of function exist within this locus. PMID- 1908398 TI - Rescue from the abnormal oocyte maternal-effect lethality by ABO heterochromatin in Drosophila melanogaster. AB - The euchromatic maternal-effect mutation abnormal oocyte (abo), of Drosophila melanogaster interacts with regions of heterochromatin known as ABO, which reside on the X, Y and second chromosomes. Here, we show that survival of progeny from abo females depends in part upon the maternal dosage of ABO heterochromatin. A comparison was made of the recovery of genotypically identical progeny from abo mothers bearing sex chromosomes of various ABO contents. The results show that the recovery of daughters was decreased if mothers were ABO-/ABO-. However, no decrease was observed if mothers were ABO+/ABO-. In addition, the survival of daughters was greater when they received an ABO-X chromosome from an ABO-/ABO+ mother rather than the father. We suggest that these results reflect a complementation or interaction between the ABO-deficient X and the ABO heterochromatin in the maternal genome. This proposed interaction could occur early in oogenesis in the mother or prior to completion of meiosis I in the fertilized egg. To determine if zygotic dosage of ABO heterochromatin might also be important at very early stages of embryogenesis, we examined the timing of zygotic rescue by paternally donated ABO heterochromatin using a second mutation, paternal loss (pal). Homozygous pal males produce progeny which lose paternally derived chromosomes during the early zygotic divisions. Zygotes that have lost a paternal sex chromosome in a fraction of their nuclei will be mosaic for the amount of ABO heterochromatin. By monitoring the recovery of pal-induced mosaics from abo and abo+ females, we could determine the temporal and spatial requirements for ABO function. Results show that the survival of progeny from the abo maternal-effect lethality was increased if ABO heterochromatin was present prior to the pal-induced loss event. Analysis of mosaic patterns did not reveal a specific lethal focus. We conclude from these results that ABO heterochromatin serves its vital function prior to completion of the early cleavage divisions in progeny of abo mothers. PMID- 1908399 TI - [Clastogenic effect of thiophosphamide in spermatogonia of inbred strains of mice]. AB - Sensitivity of spermatogonia of 11 mouse inbred strains to induction of chromosome damages by thiophosphamide (thioTEPA) was studied. Metaphase chromosome preparations were made 24 h after treatment with thioTEPA (at 2.25 mg/kg, i/p). With respect to frequency of cells with chromosome damages, strains were ranked as follows: A/Sn (17.5 + 4.4%) greater than 101/H greater than TPS greater than WR = C57BL/6 = AKR = NZB greater than CBA/Lac greater than C3H/Sn greater than MRL greater than BALB/c (5.0 + 2.2%). This distribution does not coincide with that for sensitivity of bone marrow cells, though the data support, in general, the estimations obtained earlier for strains' mutability. Comparison of the data presented with those from literature demonstrates that the sensitivity to clastogenic effect of thioTEPA (and other alkylating agents) correlates neither with spontaneous level of SCE, nor with unscheduled DNA synthesis, nor with radiosensitivity of inbred mice. The frequency of induced chromosome aberrations in spermatogonia is relatively low and spermatogonia cannot substitute bone marrow cells as a test system when assaying chemical mutagens. PMID- 1908400 TI - [Genetic structure of the Mongols as derived from the ABO, MN, Rh, EsD, GLO1, PGM1, AcP, 6-PGD, Hp, Gc, Tf, C'3 and ChE2 loci]. AB - According to integral characterization of gene frequencies of the investigated loci AB0, MN, Rh, GLO1, PGM1, EsD, AcP, 6-PGD, Hp, Tf, Gc, C'3 and ChE2, Mongolian population has high level of polymorphism, with the exception of haplotypes R" (cdE) and Ry(CdE) at the Rh locus and TfB0-1 at the Tf locus. The data on biochemical and immunological polymorphic gene markers analysed in the population of Mongolia show that the Mongolians have some distinctive features, in comparison with the mean-in-the-world characteristics: high frequencies of the B genes at the AB0 locus; D, E, R1 and R2 at the Rh locus; GLO11, PGDc, TfDChi, E2(C5+), PGM1(1+); low frequencies of the genes A(AB0), R0(Rh), AcPc, Hp1, Gc2, C'3F, PGM 1(2-); the rest of the genes at the above-mentioned loci and the genes of the locus MN have the mean-in-the-world frequencies. PMID- 1908401 TI - Immunoglobulin heavy-chain joining genes in the rat: comparison with mouse and human. AB - We have cloned by the polymerase chain reaction a 2.1-kb fragment carrying heavy chain joining (JH) gene segments and a part of the JH-C mu intron of the rat. Sequencing showed that the rat genome has four functional JH segments and that only a slight divergence has occurred after the separation of rat and mouse. A systematic sequence comparison between the two species and human revealed an additional JH pseudogene in rat and mouse 5' of JH1 which has not been described so far. The implications in evolutionary terms are discussed. In addition, we give an assessment of the misincorporation rate of the Taq polymerase. PMID- 1908402 TI - Optimization of the signal-sequence cleavage site for secretion from Bacillus subtilis of a 34-amino acid fragment of human parathyroid hormone. AB - We have effected the secretion from Bacillus subtilis of a 34-amino acid (aa) fragment of human parathyroid hormone (PTH,1-34), using a Bacillus amyloliquefaciens neutral protease signal sequence. The secretion efficiency depended on the aa sequence near the signal-sequence cleavage site. We constructed a series of gene fusions encoding different pairs of aa between the signal sequence and PTH,1-34. There was a correlation between those polypeptides which were efficiently secreted and the potential for a beta-turn in the region just beyond the signal-sequence cleavage site. Based on this correlation, we constructed a gene fusion which specified Gly rather than Ala at the C terminus of the signal sequence, thus creating a beta-turn potential at the end of the signal sequence. The change provided a slight increase in secretion efficiency. PMID- 1908404 TI - Basic physics of electron beam therapy. PMID- 1908403 TI - Genomic organization of the human-amyloid beta-protein precursor gene. PMID- 1908405 TI - Electron beam: the management of head and neck cancer. PMID- 1908406 TI - Intraoral cone for carcinoma of the oral cavity. PMID- 1908407 TI - Electron arc therapy of the chest wall for breast cancer: rationale, dosimetry, and clinical aspects. PMID- 1908409 TI - The 'boost' in the treatment of early-stage breast cancer: electrons versus interstitial implants. PMID- 1908408 TI - Breast cancer: chest wall hyperthermia-electron beam therapy. PMID- 1908410 TI - Management of vulvar cancer. PMID- 1908411 TI - Treatment of orbital lymphoid tumors with electron beams. PMID- 1908413 TI - Surgical aspects of intraoperative radiation therapy. PMID- 1908412 TI - Electron beam therapy in children. PMID- 1908414 TI - Surgical aspects of intraoperative electron beam therapy. PMID- 1908415 TI - Apparatus, technique and dosimetry of intraoperative electron beam therapy. PMID- 1908416 TI - Intraoperative radiation therapy for pancreatic, biliary and gastric carcinoma: the US experience. AB - The experience with pancreatic, biliary and gastric cancer in the US has demonstrated that IORT is technically a feasible and therapeutically relatively safe modality. However, much research remains to be done. The toxicity in humans of single large dose radiation to normal tissue has not been firmly established. Clinical studies must be able to demonstrate the efficacy of IORT as well as a therapeutic advantage for this approach. IORT is potentially a very effective adjuvant therapy in treating tumors which are technically difficult to treat surgically or which have a high rate of recurrence following radical surgery. The combination of surgery and IORT may improve local control of the tumor by removing gross disease and identifying areas of potential risk for recurrence. Regional and distant failure, however, remains a problem. Because of this, future investigations are underway to combine chemotherapy with IORT, surgery and EBRT. The effectiveness of IORT needs to be established with prospective randomized trials. The appeal of this procedure is demonstrated by its rapidly growing popularity, and this very appeal requires that the value of the procedure be determined. PMID- 1908417 TI - Intraoperative radiation therapy for carcinoma of the stomach and pancreas. PMID- 1908418 TI - Intraoperative radiotherapy in gastric and pancreatic carcinoma: a European experience. PMID- 1908420 TI - Treatment planning in electron beam therapy. PMID- 1908419 TI - Indications for and results of intraoperative irradiation for locally advanced colorectal cancer. PMID- 1908421 TI - Intraoperative radiotherapy in thoracic tumors. PMID- 1908422 TI - Intraoperative radiation therapy for prostatic cancer. PMID- 1908423 TI - Intraoperative electron beam therapy in the community environment. PMID- 1908424 TI - Radiobiological aspects of electron beams. PMID- 1908426 TI - Total skin electron beam therapy in the management of mycosis fungoides. PMID- 1908425 TI - External beam electron therapy: pitfalls in treatment planning and deliverance. PMID- 1908427 TI - Electron beam and x-rays in the treatment of epithelial skin cancer: dosimetric considerations and clinical results. PMID- 1908429 TI - Zinc(II) inhibits the release of thyroid and glucocorticoid receptors from chromatin of cultured GC cells. AB - The effect of Zn(II) on the association of thyroid and glucocorticoid hormone receptors with chromatin was studied in chromatin from cultured GC cells. Chromatin was incubated at 0-4 degrees C in 20 mM Tris, pH 7.4. When buffers contained 0.15 M NaCl, the release of T3 receptors from chromatin was time dependent; 50% of T3 receptors were released after 30 min incubation. Receptor release appeared relatively specific since less than 10% of chromatin protein and DNA, and less than 13% of chromatin zinc were released under these conditions. Addition of Zn(II) inhibited receptor release; one-half maximal inhibition occurred at 1 microM ZnCl2. Cd(II) and to a lesser extent Co(II) had similar but smaller effects. Addition of EDTA prevented this effect of Zn(II); EDTA alone enhanced receptor release. Zn(II) also inhibited the release of glucocorticoid receptors from chromatin in similar incubations. Our findings suggest that Zn(II) increases the association of hormone receptors with chromatin and, thereby, may influence receptor function. PMID- 1908428 TI - [An injury of the liver caused by ischemia-reperfusion in rat liver]. AB - Cellular damage of various organs by ischemia following reperfusion is assumed to be at least in part due to lipid peroxidation in biomembranes, and oxygen-derived free radicals play a major role. The level of lipid peroxides in liver tissue increased during 90-min ischemia. When reflow of hepatic blood was allowed, a greater increase in the lipid peroxides was observed. Similar increases were obtained in several serum markers (GOT, GPT and LDH) during the period of ischemia or ischemia-reperfusion. In addition, levels of cytochrome p-450 and NADPH cyt. c reductase activity decreased in proportion to the decrease in microsomal proteins during ischemia or ischemia-reperfusion. On the other hand, superoxide dismutase in blood was significantly increased by ischemia reperfusion. Rats died within 2 days after liver ischemia of 90 min, while all animals subjected to 30-min ischemia survived. Histopathological examinations indicated that extensive coagulation with erythrocytes occurred and the extent was dependent on the time of ischemia. The liver injury by ischemia-reperfusion could be a useful experimental model for studying liver injury induced by free radicals, for developing hepatoprotective drugs, or for investigating liver transplantation. PMID- 1908430 TI - Influence of lysine acetyl-salicylate on glucose and arginine stimulated insulin release in man. AB - In order to determine the influence of acute inhibition of prostaglandin synthesis on insulin release in man, the influence of lysine acetyl-salicylate (0.9 g) on glucose- and arginine-stimulated insulin release was studied in eight volunteers. No significant differences were found in plasma C-peptide levels between the salicylate and the control study days during administration of arginine (0.5 g/kg; 30 min) nor during a hyperglycemic clamp (glucose level 17 mMol/L; 60 minutes). These studies indicate that acute administration of salicylate does not change insulin release in man. PMID- 1908431 TI - Effect of pravastatin on newly-secreted very low density lipoprotein composition in rats. PMID- 1908432 TI - Sequence of prolactin effects on phospholipid synthesis in Nb2 node lymphoma cells. AB - In Nb2 node rat lymphoma cells, the effects of prolactin (PRL) on the rates of incorporation of several precursors into neutral lipids, phospholipids and proteins were determined. The onset of the PRL stimulation of radiolabeled precursor incorporation into lipids occurred between 1 and 4 hours after PRL addition to Nb2 cells; precursors employed included [14C]-acetate, [3H]-glycerol, [32P]O4, [3H]-choline, [3H]-ethanolamine, [3H]-serine and [3H]-myoinositol. No effects were observed during the initial 60 min of culture with PRL. The effects on precursor incorporation that occur after 1 hr of PRL exposure are likely related to the stimulation of cell growth by PRL. In cells that were prelabeled with the radiolabeled precursors and subsequently incubated with PRL, PRL had no effect on the metabolism of the radiolabeled phospholipids or the accumulation of phospholipid products until several hours after hormone addition. We would conclude from these studies that the initial (60 min) effect of PRL on Nb2 node lymphoma cells does not likely use a signal transduction mechanism that involves products derived from the cellular phospholipids. PMID- 1908434 TI - Light- and electron-microscopical study of a case of gold salt-induced hepatotoxicity. AB - A 56-yr-old woman with long-standing rheumatoid arthritis exhibited jaundice, pruritus and abdominal discomfort after 8 yr of periodic gold sodium thiomalate injections amounting to a cumulative dose in excess of 2.5 gm. Histopathological examination of the liver biopsy specimen showed submassive loss of parenchyma, collapse of reticulin and mixed cellular inflammatory infiltrates. Macrophages contained dark granules, which displayed the characteristics of aurosomes when examined by transmission electron microscopy and electron microprobe analysis. It is likely that hepatocellular injury occurred when the lysosomal storage capacity for gold was exceeded. PMID- 1908433 TI - Effects of aldose reductase inhibitor (ONO-2235) on human erythrocyte sorbitol concentrations in 75 g oral glucose tolerance tests. AB - In order to evaluate the effects of the aldose reductase inhibitor, ONO-2235, on the short-term response of human erythrocyte sorbitol to hyperglycemia in vivo, eleven diet-treated Type 2 (non-insulin-dependent) diabetic patients were studied twice in 75 g oral glucose tolerance tests - with and without ONO-2235 (200 mg p.o.) premedication. The erythrocyte sorbitol concentrations increased with the increments of blood glucose and erythrocyte glucose concentrations in the test performed without ONO-2235. The erythrocyte sorbitol response in the test performed with administration of ONO-2235 30 min prior to glucose load was lower than that in the test performed without ONO-2235 (F = 5.782, P less than 0.05). No significant differences were found between the two tests in blood glucose and erythrocyte glucose concentrations (F = 0.092, P = 0.761; F = 0.029, P = 0.860, respectively). It is concluded that human erythrocyte sorbitol concentrations change promptly in response to rapid changes in erythrocyte glucose concentrations and that administered ONO-2235 is effective in inhibiting the human erythrocyte sorbitol pathway in man. PMID- 1908435 TI - Monoclonal antibodies raised against the idiotype of the murine B cell lymphoma, BCL1 act primarily with heavy chain determinants. AB - Anti-idiotypic antibodies can be used as probes to distinguish neoplastic cells from their normal counterparts. In addition they have been used in the passive therapy of B cell tumors. In this report we describe a panel of 7 rat monoclonal antibodies raised against idiotypic determinants carried by the IgM molecule of the BCL1 lymphoma. The majority (6/7) of these antibodies recognize private idiotypic determinants that are carried on the isolated mu heavy chain of the molecule, and do not require the lambda chain for reactivity. This is unusual for antibodies raised against the idiotype of the whole immunoglobulin molecule, which normally require both chains for reactivity. The antibodies do not, however, bind peptides corresponding to the complementarity determining regions of the mu heavy chain of BCL1. The antibodies perform well in complement mediated cytotoxicity, and, in at least one case, are effective in the passive immunotherapy of BCL1 lymphoma. PMID- 1908436 TI - Effect of protein calorie malnutrition on in vitro incorporation of (U-C14) glucose in brain of young rhesus monkeys. AB - Twelve young rhesus monkeys weighing 1.5-2.0 kg were acclimatised for a month in the animal house of the Institute. After acclimatization 6 monkeys were placed on a protein calorie deficient diet and remaining 6 on normal diet. The deficiency state was indicated by reduction in body weight, significant decrease in serum albumin, lack of physical activity and shedding of fur. At this stage, animals of both groups were sacrificed and brains were removed. Cerebrum was separated, blotted on filter paper and weighed. In vitro incorporation of (U-C14)-glucose was done for 2 hr in approximately 300 mg cerebrum. Incorporation of this precursor was determined in cerebrum, lipids, its fractions and proteins in both groups. There was increased incorporation of (U-C14)-glucose into tissue, gangliosides, free fatty acids and esterified cholesterol but no significant change in myelin marker lipids and proteins in PCM group was noticed as compared to age matched controls. PMID- 1908437 TI - In vivo suppression of pituitary and circulatory follicle stimulating hormone by human seminal plasma inhibin. AB - Human seminal plasma inhibin (HSPI), of prostatic origin, has been shown to bring about a dose dependent suppression in pituitary and circulatory FSH concentrations in intact rats. No significant changes in LH levels either in pituitary or in circulation were observed at the doses used. This has further been substantiated by an immunocytochemical staining. A marked reduction in staining intensity for FSH was observed in the pituitary of inhibin treated rats as compared to the controls. None of the purified inhibin peptides from other sources have so far been reported to act on pituitary FSH in vivo. This study thus, for the first time demonstrates an in vivo effect of inhibin (HSPI) on pituitary FSH concentration and secretion. PMID- 1908438 TI - Chemopreventive efficacy of betel leaf extract and its constituents on 7,12 dimethylbenz(a)anthracene induced carcinogenesis and their effect on drug detoxification system in mouse skin. AB - Effects of topically applied betel leaf extract (BLE) and its constituents. beta carotene, alpha-tocopherol, eugenol and hydroxychavicol on 7,12 dimethylbenz(a)anthracene (DMBA) induced skin tumors were evaluated in two strains of mice. BLE, beta-carotene and alpha-tocopherol, significantly inhibited the tumor formation by 83, 86, 86% in Swiss mice and 92, 94 and 89% in male Swiss bare mice respectively. Hydroxychavicol showed 90% inhibition in Swiss bare mice at 24 weeks of treatment. Eugenol showed minimal protection in both strains of mice. The mean latency period and survivors in BLE, beta-carotene, alpha tocopherol and hydroxychavicol treated groups were remarkably high as compared to DMBA alone treated group. Intraperitoneal injection of betal leaf constituents showed a significant effect on both glutathione and glutathione S-transferase levels in the Swiss mouse skin. PMID- 1908439 TI - Electrophysiological and histopathological changes in peripheral nerves of postnatally undernourished and rehabilitated young rhesus monkeys. AB - Nerve condition velocity of ulnar and tibial nerves and qualitative histology of ulnar nerve were studied in young rhesus monkeys. Motor nerve condition velocity of both the nerves and amplitude of sensory response of ulnar nerve were significantly decreased in even moderate protein calorie malnourished (PCM) group of monkeys. Increased paranodal gap, segmental demyelination, thin myelinated fibres and prominent Schmidt Lanterman Clefts were also observed in PCM group. There was complete recovery in motor nerve conduction velocity in the nerves of both limbs while partial in amplitude of sensory response in proximal segment of ulnar nerve on nutritional rehabilitation of 10-12 weeks. PMID- 1908440 TI - NAD(P)H:quinone oxidoreductase (DT-diaphorase) activity and mRNA content in normal and neoplastic mouse lung epithelia. AB - DT-diaphorase (DTD) is a flavoprotein which catalyzes obligate two-electron reduction of a diverse group of substrates. We have reported previously that non tumorigenic mouse lung alveolar type-II pneumocytes have high DTD activity, while cell lines derived from lung tumors do not. In contrast, other investigators, using human lung tissue, reported increased DTD activity in tumors compared with normal tissue. We therefore investigated DTD associated with mouse lung neoplasia in vivo as well as in vitro. Pulmonary tumors had far less DTD activity compared with normal mouse lung. Correspondingly, a tumorigenic mouse lung cell line which arose as a spontaneous transformant of a normal cell line had very low DTD activity compared with non-tumorigenic lung cells. DTD-specific mRNA levels were also much higher in normal cell lines than in neoplastic ones. DTD was localized histochemically in type-II pneumocytes in situ, but was not observed by this technique in normal bronchiolar epithelia or in tumor cells. These data show that, unlike what has been observed in human lung cancer, a marked decrease in DTD content and activity accompanied mouse lung tumorigenesis in vivo and neoplastic transformation in vitro. PMID- 1908441 TI - Functional characterization of tumor-infiltrating lymphocytes, lymph-node lymphocytes and peripheral-blood lymphocytes from patients with breast cancer. AB - Mononuclear cell infiltration is frequently seen within human solid tumors. Effector cells within the tumor site usually fail to exhibit cytotoxic or natural killer activity when freshly isolated; however, they develop potent and sometimes specific cytotoxicity after expansion in IL2. Thus, local tumor environment may influence lymphocyte function. In our study, we disaggregated human breast-cancer and lymph-node tissue to obtain lymphocyte-enriched cell fractions. Besides phenotypic analysis, functional characterization with regard to proliferation and cytokine production of tumor-infiltrating lymphocytes (TIL), peripheral-blood lymphocytes (PBL) and lymph-node lymphocytes (LNL) was the aim of our study. TIL showed an enrichment of CD8+ cells with a corresponding decrease in CD4+ cells in comparison with PBL and LNL. In response to PHA, TIL showed decreased 3H thymidine uptake, but TIL were significantly stimulated by rhIL2. TIL produced low levels of IL2, TNF and IFN gamma upon mitogen/phorbol ester stimulation, while PBL produce high levels of TNF and IFN gamma but low levels of IL2. Under the same experimental conditions, LNL produce high levels of TNF and IL2 but low levels of IFN gamma. Mitogen-mediated TNF secretion was increased after addition of autologous tumor cells in TIL and LNL, whereas IFN gamma secretion tended to be suppressed. Our results indicate different patterns of activities of TIL, LNL and PBL from breast-cancer patients. PMID- 1908442 TI - Severe cachexia in mice inoculated with interferon-gamma-producing tumor cells. AB - Nude mice were inoculated with CHO/IFN-gamma cells, a line of Chinese hamster ovary tumor cells, that had been genetically engineered to produce murine IFN gamma. Severe cachexia, as evident from body weight loss and reduced food intake, occurred in these mice, but not in those injected with CHO/control cells, i.e. the original, non-IFN-gamma-producing line. The essential role of IFN-gamma in the pathogenesis of cachexia was confirmed by the demonstration that monoclonal antibodies (MAbs) against IFN-gamma, given prior to injection of the tumor cells, prevented cachexia. In addition to IFN-gamma, the presence of the tumor cells was also required for cachexia to develop. As evident from pair-feeding experiments, reduced food intake could only partially account for the rapid and extensive body weight loss. Cachexia was characterized by a marked reduction in the amount of interscapular fat tissue. Injected tumor cells exclusively invaded intraperitoneal adipose tissue and elicited an inflammatory cell infiltrate, indicating that interscapular fat loss was due to humoral factors. Our data suggest that, among the humoral factors responsible for cancer-associated cachexia, IFN-gamma plays a prominent role. PMID- 1908443 TI - Comparison of the serum and tissue concentrations of cefuroxime from cefuroxime axetil and phenoxymethylpenicillin in patients undergoing tonsillectomy. AB - In the study described, the pharmacokinetics of two oral betalactams, cefuroxime axetil and phenoxymethylpenicillin, were compared with respect to their penetration into tonsil tissue. Seventeen patients were given cefuroxime axetil 500 mg single dose and 16 patients were given phenoxymethylpenicillin 650 mg single dose, at different time intervals before tonsillectomy. The tonsils were freeze-dried and the drug concentrations in serum and tissue determined by a high performance liquid chromatographic method. Cefuroxime axetil showed a slightly better penetration ratio (mean 35%, median 32%) than phenoxymethylpenicillin (mean 31%, median 24%) however the difference was not statistically significant. The bioavailability of cefuroxime axetil was low due to being administered in the fasting state. The relatively low penetration ratios of both drugs into samples of whole tissue can be explained by the localization of betalactam antibiotics primarily in the extracellular fluid, with low penetration into normal cells. Both drugs were found to reach concentrations in tonsil tissue above the minimum inhibitory concentration for Group A beta-haemolytic streptococci after a single oral dose. In addition to streptococci, Haemophilus influenzae and beta-lactamase producing Staphylococcus aureus were isolated in a significant number of the tonsils. These bacteria may play a pathogenic role, but this was not investigated. PMID- 1908444 TI - Pharmacokinetics of 2',3'-dideoxyadenosine in dogs. AB - The pharmacokinetics of 2',3'-dideoxyadenosine (ddAdo) and 2'-3'-dideoxyinosine (ddIno) were determined after intravenous bolus administration and long-term intravenous infusion of ddAdo in dogs. ddAdo was rapidly deaminated to ddIno and ddAdo plasma concentrations were only a fraction of ddIno concentrations. The total body clearance of ddAdo exceeded the literature value for the cardiac output of the dog, indicating an extremely rapid metabolism, and the existence of extrahepatic metabolism. Urinary excretion of unchanged ddAdo was a minor route of elimination (approximately 1%). The pharmacokinetics of ddIno was determined assuming complete conversions of ddAdo to ddIno. ddIno elimination was dose dependent with total body clearance ranging from 4 to 55 ml/min/kg in individual animals. The plasma half-life was approximately 30 min after most routes of administration, but increased to approximately 60 min in two animals receiving a large intravenous dose of 500 mg/kg. ddIno penetrated into the cerebrospinal fluid to a limited extent, reaching concentrations of 3-11% of those in plasma. Urinary excretion of unchanged ddIno accounted for approximately 20% of the administered dose of ddAdo, while uric acid and hypoxanthine were minor urinary metabolites. Concentrations exceeding the in vitro minimal viral inhibitory concentration (2.4 micrograms/mL) could be safely maintained in plasma for a 10 day period. Infusions which gave cerebrospinal fluid concentrations of 12 to 17 micrograms/mL resulted in dose limiting myelosuppression and intestinal toxicity, after less than 10 days of infusion. Orally administered ddAdo was absorbed as ddIno, with bioavailabilities ranging from 28 to 93% in experiments where no emesis occurred. These studies indicate the rapid in vivo conversion of ddAdo to ddIno, and support the selection of ddIno over ddAdo for further drug development. PMID- 1908445 TI - Blood hypercoagulability secondary to experimental cerebral ischemia in the rabbit: influence of a hyperdyslipemia induced by an atherogenic diet. AB - Within the framework of a research carried out at the Neurological Institute of Pavia on experimental cerebral ischemia some biohumoral determinations were done on two groups of rabbits: one kept on a standard diet and the other on an atherogenic diet to induce dyslipemia. The aim was to find out whether induced ischemia produces an activation of the hemocoagulation processes and whether hyperdyslipemia constitutes an aggravating factor. In the animals on a standard diet there was a statistically significant increase in factor X A and a nonsignificant increase in parameter (r + k) on TEG (thromboelastogram) and of factor VIII C after embolization. In the hyperdyslipemic group the changes were definitely more marked and, in the case of factor VIII C and parameter (r + k), statistically significant, accompanied by slight variations in APTT and factor IX pointing in the same direction. We discuss the meaning of our findings. PMID- 1908446 TI - [Disseminated cicatricial pemphigoid]. AB - The authors describe a typical case of a rare disease, disseminated cicatricial pemphigoid. At the site of the subepidermal bulla excessive scarring in seen. Electron microscopic examination reveals elastic fibrin deposition and incipient vacuolation under the basement membrane. The indirect immunoperoxidase study shows increased numbers of positive Langerhans cells, which support their antigen presenting role. PMID- 1908447 TI - The use and acquisition of surgical laser technology. PMID- 1908448 TI - CO2 lasers. PMID- 1908449 TI - Clinical effects of pulsatile CO2 laser delivery. AB - In this article, we discuss the two most commonly used pulsatile laser-delivery modes, Superpulse and Pulser, and compare their effects with each other, as well as with Continuous Wave (CW) delivery. In addition, because a firm understanding of basic laser-tissue interactions is key to knowledgeably and sensibly using lasers, regardless of the delivery mode, we present an overview of some basic principles; readers interested in a greater level of detail should consult other sources for a fuller understanding of the issues. We also discuss current clinical perceptions surrounding the use of pulsatile modes and considerations in selecting a mode to achieve the desired effects. Although some of the concepts in this article may apply to lasers using other wavelengths, the emphasis here is primarily on CO2 lasers. PMID- 1908450 TI - Detection and identification of Listeria monocytogenes in cooked sausage products and in milk by in vitro amplification of haemolysin gene fragments. AB - Recent outbreaks of listeriosis have emphasized the urgent need for rapid and reliable detection methods for Listeria spp., especially in food. Haemolysin production is a major factor in the pathogenesis of listeriosis and the polymerase chain reaction (PCR) was used to amplify two specific DNA fragments of the alpha- and the beta-haemolysin genes. The amplification system specifically recognized L. monocytogenes strains. The detection limit determined with pure cultures was 10 bacteria when estimated with alpha-haemolysin primers. In the analysis of 50 samples of cooked sausage products, bacterial colonies suspected to be Listeria spp. were isolated by conventional methods from six samples. PCR analysis identified three of six as L. monocytogenes. Subsequent serotyping showed perfect agreement with the PCR results. Since enrichment is the most time consuming step in conventional methods a PCR procedure which allows the direct detection of L. monocytogenes in milk was developed. Pasteurized milk was artificially contaminated with various levels of L. monocytogenes. The detection limit was determined to be 10 bacteria/10 ml milk and direct detection and identification of L. monocytogenes took less than two working days. These results show that this haemolysin gene amplification system is very rapid and reliable and therefore avoids cumbersome and lengthy cultivation steps. PMID- 1908451 TI - The effects of some halogen-containing compounds on Bacillus subtilis endospores. AB - Sodium hypochlorite (NaOCl) and sodium dichloroisocyanurate (NaDCC) were more active against Bacillus subtilis 8236 spores in both viability and in germination and outgrowth studies than were polyvinylpyrrolidone-iodine (PVP-I) and Lugol's solution. Of the two chlorine compounds studied NaOCl proved to be the more active. The two iodine-containing compounds gave contrasting results with the Lugol's solution demonstrating increased antibacterial activity with increasing available iodine concentration. The antibacterial behaviour of PVP-I, however, reflected the more complex nature of aqueous iodine-surfactant mixtures. Initially, non-complexed iodine concentration (the active species) increased with increasing total available iodine concentration, resulting in increasing antibacterial activity. However, due to changes in the physical properties of the mixture, a maximum concentration of non-complexed iodine was reached so that a further increase in total available iodine resulted in a decrease in non complexed iodine concentration and consequently a decrease in the antibacterial activity of the solution was observed. A greater inhibitory effect was observed in subsequent germination and outgrowth studies when spores were pre-treated with respective biocide than when untreated spores were added to germination media containing biocide at t = 0. This may reflect a combination of different contact times plus the neutralizing effect of the germination media on such halogen compounds. PMID- 1908452 TI - Determination of penicillin G residues in edible animal tissues by liquid chromatography. AB - An improved method has been developed for the determination of benzyl penicillin in animal tissues. Tissues are fortified with a known amount of penicillin V (internal standard) and extracted with water. The extract is deproteinized with sulfuric acid and sodium tungstate, filtered, and concentrated on a conditioned C18 solid phase extraction column. Penicillin V and benzyl penicillin are then eluted from the column with 1 mL 60% acetonitrile-35% water-5% 0.2M phosphate buffer solution and derivatized with 1 mL 1,2,4-triazole-mercuric chloride solution at 65 degrees C for 30 min. An aliquot of this sample is analyzed by reverse phase liquid chromatography with UV detection at 325 nm. The limit of detection is 5 micrograms/kg (ppb) penicillin G (8.4 IU/kg) in liver, kidney, and muscle tissues). PMID- 1908453 TI - A resuscitation/selection system for rapid determination of Salmonella in foods. AB - A resuscitation medium was developed consisting of a trypticase soy broth base supplemented with 0.5% yeast extract, 0.25% sodium pyruvate, 0.01% sodium thioglycollate, and 0.1% chicken fat. After a resuscitation period of 4 h, the medium was made selective by addition of either sodium thiosulfate, bile salts and iodine, or sodium selenite and L-cystine. The now selective medium was incubated for 16 h. The presence or absence of Salmonella was determined by the Salmonella-Tek antibody-based detection kit. The present system was compared with a method of the Bacteriological Analytical Manual (BAM) for naturally contaminated foods. Nineteen egg products were screened; 3/19 were positive using the BAM method, 9/19 were positive using the present system. Seventeen chicken samples were assayed; 10/17 were positive using the BAM method; 13/17 were positive using the present system. Of 8 pepper samples, 4/8 were positive using the BAM method; 6/8 were positive using the present system. Of 8 spice samples, 6/8 were positive using the BAM method, 7/8 were positive using the present system. Of 6 onion products sampled, 5/6 were positive using the BAM method; 6/6 were positive using the present system. PMID- 1908454 TI - Rapid immunochemical screening method for aflatoxin B1 in human and animal urine. AB - A method has been developed to determine the presence of aflatoxin B1 in the urine of animals (including humans) by utilizing commercial immunochemical kits that can be used in the field. Urine is treated with diatomaceous earth and filtered to clarify the sample; 2-3 ppb aflatoxin B1, corresponding to about 300 ppb in the ingested feed/food, can be detected in the filtered urine without further purification. To improve sensitivity, the urine filtrate is passed through a C18 solid phase column to extract the aflatoxin. The column is washed with acetonitrile-water (15 + 85) and water, aflatoxin B1 is eluted with methanol water (7 + 3), and water is added to the eluate, which is then tested for aflatoxin with the test kit. The limit of detection is 0.2 ppb, reflecting consumption of 40 ppb or more aflatoxin in the feed/food. When the initial sample volume is adequate, purification through the C18 column step is usually sufficient. For limited sample volumes, the eluate from the C18 column is mixed with water, added to an immunosorbent affinity column, and washed with water to remove excess sample matrix and impurities. Aflatoxin B1 is eluted with acetonitrile. The extract is evaporated under nitrogen and the residue is redissolved in methanol-water (25 + 75). At this purification stage, the limit of detection is reduced to 0.05 ppb. PMID- 1908455 TI - Vasoactive intestinal peptide hydrolysis by antibody light chains. AB - This paper describes evidence for hydrolysis of a neuropeptide, vasoactive intestinal peptide (VIP), by light chains purified from the IgG of a human subject positive for VIP binding antibodies. Purified IgG was digested with papain, resultant fragment antigen binding (Fab) fragments were reduced with 2 mercaptoethanol and alkylated with iodoacetamide, and light chains were purified by chromatography on immobilized antibodies to light chains and immobilized antibodies to heavy chains. Non-immunoglobulin components were undetectable in the light chain preparation, judged by sodium dodecyl sulfate-electrophoresis and Western blotting with anti-heavy and anti-light chain antibodies. The light chains hydrolyzed VIP with specific activity 32-fold greater than that of Fab, the pH optimum for light chain-mediated VIP hydrolysis was 7.0-7.5, and the hydrolytic activity was saturable (Vmax, 0.19 pmol/min/microgram light chains; substrate concentration at Vmax/2,380 nM). PMID- 1908456 TI - Fluoride is not an activator of the smaller (20-25 kDa) GTP-binding proteins. AB - Effects of aluminum, magnesium, and fluoride (AMF) on members of both the trimeric G protein and smaller (20-25 kDa) monomeric GTP-binding protein families were examined. The dissociation of GDP from G proteins was blocked by AMF but was unchanged with the addition of AMF to any of six of the monomeric GTP-binding proteins. Biochemical activities and properties of one of the smaller GTP-binding proteins, ADP-ribosylation factor, were also found to be unaffected by AMF. It is concluded that the ability of AMF to activate the trimeric G proteins is not shared by the smaller GTP-binding proteins and thus should prove to be a useful discriminator between cellular activities regulated by these two families of regulatory proteins. PMID- 1908458 TI - Arachidonic acid release from diacylglycerol in human neutrophils. Translocation of diacylglycerol-deacylating enzyme activities from an intracellular pool to plasma membrane upon cell activation. AB - We have studied the capacity of human neutrophils to release arachidonic acid from diacylglycerol, employing 1-stearoyl-2-[1-14C]arachidonoyl-sn-glycerol and 1 [1-14C]stearoyl-2-arachidonoyl-sn-glycerol as exogenous substrates. We have found that arachidonic acid is removed from diacylglycerol by the sequential action of two enzymes. First, the sn-1 position is split by 1-diacylglycerol lipase activity, and then, arachidonic acid is released from the resulting 2 monoacylglycerol by a 2-monoacylglycerol lipase. The specific activity of the 2 monoacylglycerol lipase, using 2-[1-14C]arachidonoyl-sn-glycerol as exogenous substrate, was at least 9-fold higher than that of 1-diacylglycerol lipase, indicating that the action of the 1-diacylglycerol lipase is the rate-limiting step in arachidonic acid release from diacylglycerol. Postnuclear supernatants from A23187-treated cells showed a 2.5-fold increase in both lipase activities. The arachidonic acid-releasing diacylglycerol lipase system showed an optimum pH of 4.5 and was not inhibited by EGTA or stimulated by Ca2+, Mg2+, Mn2+, Zn2+, or Co2+. However, arachidonic acid release was inhibited by Hg2+, suggesting the involvement of sulfhydryl groups in catalytic activity. The subcellular distribution of both 1-diacylglycerol lipase and 2-monoacylglycerol lipase activities was examined in resting and A23187-treated human neutrophils by fractionation of postnuclear supernatants on continuous sucrose gradients. Both lipases were localized mainly in the membrane of gelatinase-containing granules, which were resolved from cytosol, plasma membrane, phosphasomes, and specific and azurophilic granules. When neutrophils were stimulated by the calcium ionophore A23187, a drastic shift of the 1-diacylglycerol lipase and 2-monoacylglycerol lipase toward the plasma membrane was detected. This shift was due to fusion of gelatinase-containing granules with the plasma membrane upon neutrophil stimulation. As a result of the membrane fusion process, the capacity to release arachidonic acid from diacylglycerol was increased. This translocation from the membrane of gelatinase-containing granules to the plasma membrane may play an important role in regulating the diacylglycerol level in stimulated human neutrophils. PMID- 1908457 TI - Two glycogen synthase isoforms in Saccharomyces cerevisiae are coded by distinct genes that are differentially controlled. AB - In previous work, we identified a Saccharomyces cerevisiae glycogen synthase gene, GSY1, which codes for an 85-kDa polypeptide present in purified yeast glycogen synthase (Farkas, I., Hardy, T.A., DePaoli-Roach, A.A., and Roach, P.J. (1990) J. Biol. Chem. 265, 20879-20886). We have now cloned another gene, GSY2, which encodes a second S. cerevisiae glycogen synthase. The GSY2 sequence predicts a protein of 704 residues, molecular weight 79,963, with 80% identity to the protein encoded by GSY1. Amino acid sequences obtained from a second polypeptide of 77 kDa present in yeast glycogen synthase preparations matched those predicted by GSY2. GSY1 resides on chromosome VI, and GSY2 is located on chromosome XII. Disruption of the GSY1 gene produced a strain retaining about 85% of wild type glycogen synthase activity at stationary phase, while disruption of the GSY2 gene yielded a strain with only about 10% of wild type enzyme activity. The level of glycogen synthase activity in yeast cells disrupted for GSY1 increased in stationary phase, whereas the activity remained at a constant low level in cells disrupted for GSY2. Disruption of both genes resulted in a viable haploid that totally lacked glycogen synthase activity and was defective in glycogen deposition. In conclusion, yeast expresses two forms of glycogen synthase with activity levels that behave differently in the growth cycle. The GSY2 gene product appears to be the predominant glycogen synthase with activity linked to nutrient depletion. PMID- 1908459 TI - Determination of and corrections to sequences of turkey and chicken troponins-C. Effects of Thr-130 to Ile mutation on Ca2+ affinity. AB - Reported differences in the primary structures of chicken muscle troponin C (Wilkinson, J.M. (1976) FEBS Lett. 70, 254-256) and recombinant protein deduced from a chick muscle cDNA (Reinach, F.C. and Karlsson, R. (1988) J. Biol. Chem. 263, 2371-2376) have been reinvestigated. The complete amino acid sequence of turkey muscle troponin C has also been elucidated. Residue 100, originally reported as Asp in the chicken muscle protein, is shown to be Asn in all three structures. The three amino acid sequences are identical except as follows: 1) the blocked NH2-terminal Ala at residue 1 of the chicken protein is replaced by nonblocked Met-Ala in the recombinant protein and by nonblocked Pro in turkey troponin-C; 2) residue 130 is Thr in both avian muscle proteins but Ile in the recombinant protein; 3) Asp-133 in the chicken muscle and recombinant troponins-C is replaced by Glu in the turkey protein; 4) residue 99, originally identified as Glu in the x-ray structure of the turkey protein, is shown to be Ala in all three proteins. Calcium titration of the metal-induced conformational transition of the protein as monitored by far UV CD measurements indicated a significant decrease in Ca2+ affinity of the high-affinity sites in the case of the recombinant protein as compared with the chicken muscle protein. Both pairs of sites showed high cooperativity. That this decreased Ca2+ affinity could be attributed to different amino acid residues at position 130 and not to the differences at the NH2 termini was confirmed by site-specific mutation of Ile-130 to Thr in the recombinant protein. The mutated recombinant protein now titrated identically to the chicken muscle protein. Thr-130, whereas over 21 A from the metal of sites III and IV, is involved in a hydrogen bonding network with structured water and the NH2-terminal region of helix G. PMID- 1908460 TI - Specific inhibition of protein kinase A in granulosa cells abolishes gonadotropin regulation of the proopiomelanocortin promoter. AB - Gonadotropins (follicle-stimulating hormone (FSH), luteinizing hormone, and human chorionic gonadotropin) and beta-adrenergic agonists have been shown to stimulate expression of the proopiomelanocortin (POMC) gene in ovarian granulosa cells. The current studies investigate the intracellular mechanisms by which gonadotropins regulate gene expression. Primary cultures of rat granulosa cells were transfected with the plasmid POMC-CAT-150, which expresses the chloramphenicol acetyltransferase (CAT) reporter gene under the regulation of the rat POMC 5' flanking region. CAT activity was stimulated by treatment of the cells with either 20 ng/ml FSH or 1 microM isoproterenol. To assess the role of protein kinase A (ATP:protein phosphotransferase; EC 2.7.1.37) in the gonadotropin and adrenergic response, an expression vector, MtR-AB, encoding a mutant RI regulatory subunit was cotransfected with POMC-CAT-150. The mutant protein kinase A regulatory subunit encoded by MtR-AB lacks functional cAMP-binding sites but effectively binds and specifically inhibits the catalytic activity of protein kinase A. The results of this analysis demonstrated that gonadotropin and adrenergic agonist stimulation of the POMC-CAT reporter construct in primary cultures of rat granulosa cells were abolished by cotransfection with MtR-AB; whereas a control SV40-promoter construct was unaffected by either gonadotropin treatment or cotransfection with MtR-AB. Basal expression directed by the POMC promoter was also decreased by cotransfection with the MtR-AB, implying that basal expression from the POMC promoter may also depend on protein kinase A. Deletion analysis of the POMC sequence indicated regions (-40 to -33 and +4 to +63) important for basal and FSH-stimulated expression. These studies suggest that both gonadotropin and adrenergic stimulation of the POMC promoter are mediated by protein kinase A and that regions proximal to the promoter are essential for gonadotropin-regulated expression from the promoter. PMID- 1908461 TI - Structural organization of the pigment cell-specific gene located at the brown locus in mouse. Its promoter activity and alternatively spliced transcript. AB - The pigment cell-specific gene, located at the brown (b) locus in mouse, has been cloned and characterized. Its gene product is required for the formation of black melanin rather than brown, although its exact function remains to be elucidated. We thus tentatively named it b-locus protein in this report. The b-locus protein gene is about 18 kilobase pairs long and organized into 8 exons and 7 introns. Functional analysis of its promoter region suggests that the nucleotide residues 38/154 is sufficient to direct the pigment cell-specific transcription in melanoma whole cell extracts. On the other hand, we were unable to detect its transcripts in HeLa whole cell extracts. Sequence comparison with the promoter region of the tyrosinase gene, another pigment cell-specific gene, reveals that two elements of the b-locus protein gene (-33/-24 and 18/28) are also conserved in the tyrosinase gene at equivalent positions, suggesting that these two elements may be involved in their pigment cell-specific transcription. Furthermore, we have cloned a cDNA, pMT3, coding for an isoform of b-locus protein from a cDNA library of mouse B16 melanoma cells. Sequence analysis of pMT3 reveals a deletion of 103 base pairs, which corresponds to the 5'-end of the exon 8 of the b-locus protein gene, indicating that pMT3 represents a mRNA species generated by alternative splicing. Since this deletion changes the reading frame and eliminates the transmembrane domain of b-locus protein, the pMT3-type mRNA may code for a soluble isoform. Such an isoform, consisting of 553 amino acids, differs only in its carboxyl terminus and is larger than b-locus protein by 16 amino acids. Using transient expression assays, we confirmed that such an isoform is able to react with anti-b-locus protein monoclonal antibody, TMH-1, suggesting that a b-locus protein isoform may have some function in pigmentation. PMID- 1908462 TI - Alterations in mRNA levels, expression, and function of GTP-binding regulatory proteins in adipocytes from obese mice (C57BL/6J-ob/ob). AB - Messenger RNA levels for the alpha subunit of G-proteins expressed in adipocytes of lean and obese (ob/ob) mice were compared with relative levels of the encoded proteins. Using both toxin labeling and Western blots, expression of Gs alpha, Gi alpha-1, and Gi alpha-3 was decreased by approximately 2-fold in adipocytes of obese mice, while levels of Gi alpha-2 did not differ between the phenotypes. The decreases in Gi alpha-1 and Gs alpha in the obese mouse were attributed to decreased mRNA levels for these proteins. Similar mRNA levels for Gi alpha-3 were noted in both phenotypes, but Gi alpha-2 message was increased 2-fold in the obese mouse. Inhibitory regulation of adipocyte adenylylcyclase through G proteins was evaluated by comparing the ability of R-PIA to inhibit isoproterenol stimulated responses between the phenotypes. In spite of the decrease in Gi alpha 1 and Gi alpha-3 in adipocytes from obese mice, R-PIA inhibited adenylylcyclase, cAMP-dependent protein kinase, and lipolysis in similar fashion in both phenotypes. The GTP analog, Gpp(NH)p also inhibited forskolin-stimulated adenylylcyclase in a comparable manner, but the magnitude of the inhibition was slightly less in adipocyte membranes from obese mice. In contrast, the decrease in expression of Gs alpha was translated into substantially poorer activation of isoproterenol-stimulated responses in the obese mouse. The concentration of isoproterenol producing half-maximal activation of adenylylcyclase, protein kinase, and lipolysis did not differ between the phenotypes, but the maximal responses were much lower in cells from obese mice. Similar lipolytic potential in isolated adipocytes from each phenotype and similar total forskolin-stimulated cyclase activity in adipocyte membranes from each phenotype suggest that decreased expression of Gs alpha may contribute to the characteristic alteration in mobilization of triglycerides noted in adipocytes from obese mice. PMID- 1908463 TI - Inactivation of mRNA cap-binding protein complex in Drosophila melanogaster embryos under heat shock. AB - We have studied the role of Drosophila 35-kDa cap-binding protein (CBP) and CBP complex in the mechanism of messenger RNA discrimination established in heat shocked Drosophila embryos. Drosophila 35-kDa CBP is functionally equivalent to the mammalian eucaryotic initiation factor (eIF)-4E and CBP complex, which includes eIF-4E, might be the counterpart of mammalian eIF-4F. By using anti-eIF 4E antibodies, we found that although translation of the bulk of normal messengers in Drosophila lysates was very dependent on eIF-4E, the mRNAs for the heat shock proteins (hsps) (particularly hsp70 mRNA and with the exception of hsp83 mRNA) were translated almost independently of this factor, suggesting that they may have unstructured leaders. Accordingly, hsp70 mRNA and, to a lesser extent, the mRNAs for the small hsps were found to be more resistant to inhibition by K+ than normal and hsp83 mRNAs. Moreover, Drosophila CBP complex was able to rescue partial but specifically the synthesis of normal proteins when added to a lysate from heat-shocked embryos. However, no significant effect was obtained by Drosophila eIF-4E or eIF-2. Consistent with these results, we found a great decrease in the amount of the CBP complex purified from heat-shocked embryos as compared with normal ones, whereas the amounts of free eIF-4E purified from either source were similar. Together, the above results suggest that some modification leading to the disruption of Drosophila CBP complex may account, at least to some extent, for the mRNA discrimination established in heat-shocked Drosophila embryos. PMID- 1908464 TI - Involvement of calcium in the mevalonate-accelerated degradation of 3-hydroxy-3 methylglutaryl-CoA reductase. AB - 3-Hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase), the rate limiting enzyme in the biosynthesis of cholesterol and isoprenoids, is subject to rapid degradation which is regulated by mevalonate (MVA)-derived metabolic products. HMG-CoA reductase is an integral membrane protein of the endoplasmic reticulum, the largest nonmitochondrial pool of cellular Ca2+. To assess the possible role of Ca2+ in the regulated degradation of HMG-CoA reductase, we perturbed cellular Ca2+ concentration and followed the fate of HMG-CoA reductase and of HMGal, a fusion protein consisting of the membrane domain of HMG-CoA reductase and the soluble bacterial enzyme beta-galactosidase. The degradation of HMGal mirrors that of HMG-CoA reductase, demonstrating that the membrane domain of HMG-CoA reductase is sufficient to confer regulated degradation (Skalnik, D.G., Narita, H., Kent, C., and Simoni, R.D. (1988) J. Biol. Chem. 263, 6836 6841; Chun, K.T., Bar-Nun, S., and Simoni, R.D. (1990) J. Biol. Chem. 265, 22004 22010). In this study we show that the MVA-dependent accelerated rates of degradation of HMG-CoA reductase and HMGal in cells maintained in Ca(2+)-free medium are 2-3-fold slower than the rate of degradation in cells grown in high (1.8-2 mM) Ca2+ concentration. This effect is reversed upon addition of Ca2+ to the medium. Furthermore, when cells maintained in high Ca2+ are treated with 1 microM ionomycin, the MVA-dependent accelerated degradation of HMG-CoA reductase and HMGal is also reduced about 2-3-fold. This inhibition is not due to a Ca(2+) dependent uptake or incorporation of MVA into sterols, since these processes are not affected in the absence of external Ca2+. In addition, cobalt, a known antagonist of Ca(2+)-dependent cellular functions, totally abolishes (IC50 = 520 microM in the presence of 1.8 mM extracellular Ca2+) the MVA-accelerated degradation of HMGal. These results suggest that Ca2+ plays a major role in the regulated degradation of HMG-CoA reductase. PMID- 1908465 TI - Synthetic fragments of the CD4 receptor cytoplasmic domain and large polycations alter the activities of the pp56lck tyrosine protein kinase. AB - In CD4+ T cells, the src-like tyrosine kinase pp56lck is associated with the CD4 receptor and cross-linking of CD4 results in the activation of this enzyme. The mechanism responsible for this activation is not known, although there is evidence that the activities of the src family of enzymes are regulated by tyrosine phosphorylation. Here we report that pp56lck-catalyzed angiotensin II phosphorylations are activated 20-fold in vitro by synthetic peptides reproducing portions of the murine CD4 cytoplasmic domain. This activation is described by a dissociation constant of about 2 microM. The pp56lck-catalyzed phosphorylation of other peptide substrates are effected less and in one case not at all by the peptide modulators, indicating that these CD4 sequences alter the substrate specificity of pp56lck. In contrast, peptides reproducing sequences from the CD8 receptor have a charge and size similar to the CD4 peptides, yet are vastly less effective at modulating pp56lck activities. High ionic strengths inhibit the CD4 peptide-induced modulation of pp56lck phosphotransferase activities, suggesting that charge-charge interactions are important for this process. In addition, the modulation of pp56lck activities by peptides reproducing the CD4 cytoplasmic domain are reproduced by polycations significantly larger than the CD4 cytoplasmic domain but not by those of similar size. The modulations both by CD4 peptides and the polycations do not depend on enzyme tyrosine phosphorylations. PMID- 1908466 TI - Arthropathy of the ankle in hemophilia. AB - Seventy-five patients who had hemophilia were followed clinically and roentgenographically to assess the prevalence of hemarthrosis and the prevalence and severity of arthropathy of the ankle. The mean age of the patients at the time of follow-up was twenty-two years and seven months. The patients were divided into four age-groups: less than ten years (eleven patients), ten to nineteen years (twenty-one patients), twenty to thirty years (twenty-four patients), and more than thirty years (nineteen patients). Intra-articular bleeding occurred more frequently in the joints of the lower extremities than in the joints of the upper extremities. During the second decade of life, hemarthroses occurred more often in the ankle than in the knee. A history of recurrent bleeding into the ankle joint, chronic synovitis, and overgrowth of the medial portion of the distal tibial epiphysis was associated with an early onset of arthropathy. In older patients, compression arthrodesis of the ankle joint was helpful in eliminating pain, recurrent bleeding, and equinus deformity. PMID- 1908467 TI - Characterization of aggregating proteoglycans from the proliferative, maturing, hypertrophic, and calcifying zones of the cartilaginous physis. AB - The introduction of a new microanalytical approach has made it possible to investigate the molecular structure and content of proteoglycans within the extracellular matrix of the physis when the volumes of the matrix and the cells change before mineralization of the extracellular matrix. By using extracts of serial frozen sections with a combination of gel chromatography and chemical, radioimmunoassay, and morphometric analyses, we demonstrated that, in the bovine fetal physis, the content of large aggregating proteoglycans reaches a maximum in the extracellular matrix of the hypertrophic zone, in the region where calcification begins, at the time when calcification starts. Morphometric analyses revealed that, at this time, the volume of matrix is reduced to a minimum. There was no evidence that the remaining proteoglycans were reduced in size, nor was aggregation changed at the time when calcification was initiated. Thus, contrary to earlier reports, there is no indication that these molecules need to be degraded and removed for calcification to begin, although a progressive loss of proteoglycans clearly occurs as the volume of the matrix is reduced.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1908469 TI - Cytoplasmic and transmembrane domains of integrin beta 1 and beta 3 subunits are functionally interchangeable. AB - Integrin beta subunits combine with specific sets of alpha subunits to form functional adhesion receptors. The structure and binding properties of integrins suggest the presence of domains controlling at least three major functions: subunit association, ligand binding, and cytoskeletal interactions. To more carefully define structure/function relationships, a cDNA construct consisting of the extracellular domain of the avian beta 1 subunit and the cytoplasmic and transmembrane domains of the human beta 3 subunit was prepared and expressed in murine 3T3 cells. The resulting chimeric beta 1/3 subunit formed heterodimers with alpha subunits from the beta 1 subfamily, could not interact with alpha IIb from the beta 3 subfamily, was targeted to focal contacts, and formed functional complexes within the focal contacts. A second cDNA construct was prepared that coded for an avian beta 1 subunit without a transmembrane or cytoplasmic domain. This subunit was not found in association with an accompanying alpha subunit, nor was it found expressed on the cell surface. Instead, it accumulated in vesicles within the cytoplasm and was eventually shed from the cell. The results from studies of the behavior of these two cDNA constructs demonstrate that the transmembrane and cytoplasmic domains play no role in alpha subunit selection, that the cytoplasmic domain of beta 3 is capable of functioning in the context of alpha subunits with which it is not normally paired, and that both integrin subunits must be membrane associated for normal assembly and transport to cell surface adhesive structures. PMID- 1908468 TI - NGF-induction of the metalloproteinase-transin/stromelysin in PC12 cells: involvement of multiple protein kinases. AB - In previous work, we found that nerve growth factor (NGF) induced expression of the mRNA transcript encoding the metalloproteinase transin/stromelysin in PC12 cells. Transin was found, moreover, to be a "late" gene product whose expression correlated with neurites extension. In this study, various aspects of the NGF intracellular signaling pathway in PC12 cells are investigated. We show that the protein kinase inhibitor staurosporine, but not various other kinase inhibitors, specifically blocked the NGF induction of transin. Preliminary characterization of this staurosporine-sensitive kinase suggest that it does not correspond to a tyrosine kinase, nor various serine kinases, and that it is involved both at the transcriptional and posttranscriptional levels of transin gene regulation. In contrast to these effects of staurosporine, various activators of protein kinases C and A augmented the NGF induction of transin. Similar effects of these kinase inhibitors and activators were also observed with the expression of various immediate-early genes that have been proposed to mediate the transcriptional effects of NGF, including c-fos and c-jun. These data suggest, therefore, that the NGF induction of transin mRNA expression involves multiple protein kinases acting at a number of postreceptor regulatory steps in the NGF signaling pathway. PMID- 1908470 TI - Stage-specific assays for coated pit formation and coated vesicle budding in vitro. AB - Internalization of biotin-S-S-125I-transferrin (125I-BSST) into semiintact A431 cells were assessed by two different criteria which have allowed us to distinguish partial reactions in the complex overall process of receptor-mediated endocytosis. Early events resulting in the sequestration of ligand into deeply invaginated coated pits were measured by inaccessibility of 125I-BSST to exogenously added antibodies. Later events involving coated vesicle budding and membrane fission were measured by resistance of 125I-BSST to reduction by the membrane impermeant-reducing agent, MesNa. Acquisition of Ab inaccessibility occurred very efficiently in this cell-free system (approximately 50% of total cell-associated 125I-BSST became inaccessible) and could be inhibited by anti clathrin mAbs and by antibodies directed against the cytoplasmic domain of the transferrin-receptor. In contrast, acquisition of MesNa resistance occurred less efficiently (approximately 10-20% of total cell-associated 125I-BSST) and showed differential sensitivity to inhibition by anti-clathrin and anti-transferrin receptor mAbs. Both partial reactions were stimulated by ATP and cytosol; indicating at least two ATP-requiring events in receptor-mediated endocytosis. The temperature dependence of both reactions was similar to that for 125I-BSST internalization in intact cells with no activity being observed below 10 degrees C. Morphological studies using gold-labeled ligands confirmed that internalization of transferrin receptors into semiintact A431 cell occurred via coated pits and coated vesicles and resulted in delivery of ligand to endosomal structures. PMID- 1908471 TI - Reconstitution of clathrin-coated pit budding from plasma membranes. AB - Receptor-mediated endocytosis begins with the binding of ligand to receptors in clathrin-coated pits followed by the budding of the pits away from the membrane. We have successfully reconstituted this sequence in vitro. Highly purified plasma membranes labeled with gold were obtained by incubating cells in the presence of anti-LDL receptor IgG-gold at 4 degrees C, attaching the labeled cells to a poly L-lysine-coated substratum at 4 degrees C and then gently sonicating them to remove everything except the adherent membrane. Initially the gold label was clustered over flat, clathrin-coated pits. After these membranes were warmed to 37 degrees C for 5-10 min in the presence of buffer that contained cytosol extract, Ca2+, and ATP, the coated pits rounded up and budded from the membrane, leaving behind a membrane that was devoid of LDL gold. Simultaneous with the loss of the ligand, the clathrin triskelion and the AP-2 subunits of the coated pit were also lost. These results suggest that the budding of a coated pit to form a coated vesicle occurs in two steps: (a) the spontaneous rounding of the flat lattice into a highly invaginated coated pit at 37 degrees C; (b) the ATP, 150 microM Ca2+, and cytosolic factors(s) dependent fusion of the adjoining membrane segments at the neck of the invaginated pit. PMID- 1908473 TI - Leukemia inhibitory factor: a biological perspective. AB - The notion that a single hormone may exert a broad range of effects has become well established. As such, leukemia inhibitory factor (LIF) is a prime example. LIF was initially described, purified, and genetically cloned on the basis of its ability to induce the differentiation and suppress the clonogenicity of the monocytic leukemia cell line, M1. Subsequently, it has become apparent that in vitro LIF inhibits the differentiation of pluripotential ES cells, stimulates the synthesis of hepatic acute-phase proteins, induces a switch in neurotransmitter phenotype from adrenergic to cholinergic, suppresses adipocyte lipoprotein lipase activity, and results in an increase in bone resorption. Moreover, elevation of LIF levels in vivo has a number of patho-physiological consequences, many of which parallel those effects observed in vitro. The challenge that lies ahead is to determine whether other sites of LIF action exist and to define more clearly the physiological role LIF plays in vivo. A major mechanism of cell-cell communication is by the production and secretion of polypeptide hormones by one cell type, which act either systemically or locally, via interaction with specific receptors on the surface of responsive cells. Recently, it has become apparent that hormones initially described and named, on the basis of a specific action, in many cases exert a spectrum of effects on a broad range of cell types. Moreover, the effects exerted are often mimicked closely by other hormones. Hormones that act in a pleiotropic manner are, for example, transforming growth factor-beta (TGF-beta), the various fibroblast growth factors (FGFs), interleukin 6 (IL-6), and leukemia inhibitory factor (LIF). This review will focus on the various biological effects ascribed to LIF. PMID- 1908474 TI - CBF measured by Xe-CT: approach to analysis and normal values. AB - Normal reference values and a practical approach to CBF analysis are needed for routine clinical analysis and interpretation of xenon-enhanced computed tomography (CT) CBF studies. We measured CBF in 67 normal individuals with the GE 9800 CT scanner adapted for CBF imaging with stable Xe. CBF values for vascular territories were systematically analyzed using the clustering of contiguous 2-cm circular regions of interest (ROIs) placed within the cortical mantle and basal ganglia. Mixed cortical flows averaged 51 +/- 10ml.100g-1.min-1. High and low flow compartments, sampled by placing 5-mm circular ROIs in regions containing the highest and lowest flow values in each hemisphere, averaged 84 +/- 14 and 20 +/- 5 ml.100 g-1.min-1, respectively. Mixed cortical flow values as well as values within the high flow compartment demonstrated significant decline with age; however, there were no significant age-related changes in the low flow compartment. The clustering of systematically placed cortical and subcortical ROIs has provided a normative data base for Xe-CT CBF and a flexible and uncomplicated method for the analysis of CBF maps generated by Xe-enhanced CT. PMID- 1908472 TI - Muscle abnormalities in Drosophila melanogaster heldup mutants are caused by missing or aberrant troponin-I isoforms. AB - We have investigated the molecular bases of muscle abnormalities in four Drosophila melanogaster heldup mutants. We find that the heldup gene encodes troponin-I, one of the principal regulatory proteins associated with skeletal muscle thin filaments. heldup3, heldup4, and heldup5 mutants, all of which have grossly abnormal flight muscle myofibrils, lack mRNAs encoding one or more troponin-I isoforms. In contrast, heldup2, an especially interesting mutant wherein flight muscles are atrophic, synthesizes the complete mRNA complement. By sequencing mutant troponin-I cDNAs we demonstrate that the molecular basis for muscle degeneration in heldup2 is conversion of an invariant alanine residue to valine. We finally show that degeneration of heldup2 thin filament/Z-disc networks can be prevented by eliminating thick filaments from flight muscles using a null allele of the sarcomeric myosin heavy chain gene. This latter observation suggests that actomyosin interactions exacerbate the structural or functional defect resulting from the troponin-I mutation. PMID- 1908475 TI - Determination of L-3,4-dihydroxyphenylalanine in biological fluids and tissues. PMID- 1908476 TI - Determination of human urinary hyaluronic acid, chondroitin sulphate and dermatan sulphate as their unsaturated disaccharides by high-performance liquid chromatography. AB - A method for the determination of hyaluronic acid (HA), chondroitin sulphate (CS) and dermatan sulphate (DS) was developed. HA, CS and DS were converted to the corresponding unsaturated disaccharides by digestion with chondroitinase ABC and/or chondroitinase AC-II and determined by high-performance liquid chromatography with fluorimetric detection using 2-cyanoacetamide as a post column derivatization reagent. The calibration graphs for the unsaturated disaccharides were linear over the range 2 ng - 2 micrograms for each unsaturated disaccharide. This method was applied to the analysis of normal human urine. PMID- 1908477 TI - Capillary gas chromatographic-electron-capture assay for the aldose reductase inhibitor imirestat in lens and plasma. AB - A sensitive and selective gas chromatographic-electron-capture assay was developed for the determination of the aldose reductase inhibitor imirestat in lens and plasma. The method involves solid-phase extraction of drug and internal standard from the plasma specimen or lens sample homogenate using "Baker"-10 SPE extraction columns followed by derivatization with pentafluorobenzyl bromide and further purification. Derivatives of drug and internal standard were separated on a fused-silica capillary column and analyzed using a 63Ni electron-capture detector. The limit of detection was 2.5 ng per lens or ml of plasma. The method was used to evaluate the pharmacokinetics of imirestat in human subjects and to quantitate imirestat in animal lens tissue following topical ocular administration. PMID- 1908478 TI - Effect of superovulation with human menopausal gonadotropins on growth hormone levels in women. AB - GH synthesis and secretion are influenced by several factors, including age, body weight, and sex steroid hormones. Endogenous and exogenous estrogens influence the circulating levels of GH. The purpose of the present investigation was to define the relationship between serum GH and estradiol levels during the follicular phase in women with normal ovulatory menstrual cycles compared with that in women undergoing superovulation with human menopausal gonadotropins (hMG) alone or hMG plus GnRH agonists during treatment for infertility. Serum GH and estradiol levels were determined by immunoassay in eight women during the follicular phase of a spontaneous natural cycle (group I). Thirty women underwent ovulation induction with hMG alone (group II), and 30 women received GnRH agonists followed by hMG (group III). During the follicular phase estradiol levels increased gradually in group I and reached a peak estradiol level of 1.19 +/- 0.2 nmol/L (mean +/- SEM). As expected, estradiol levels rose faster and reached higher levels in groups II and III (5.44 +/- 0.62 and 8.73 +/- 0.91 nmol/L, respectively). Whereas serum GH levels increased minimally in group I, reaching a peak level of 2.54 +/- 1.15 nmol/L, serum GH concentrations increased markedly after day 8 in groups II and III, reaching peak levels of 8.70 +/- 1.58 and 7.54 +/- 1.12 nmol/L, respectively (P less than 0.01). Basal to peak GH levels were higher in groups II and III than in group I. In summary, there are modest increases in GH levels during the follicular phase of the normal menstrual cycle, but the levels are markedly increased during superovulation with hMG or hMG plus GnRH agonists, and parallel increases in estradiol levels. PMID- 1908479 TI - Maturation of hypothalamic-pituitary-gonadal function in normal human fetuses: circulating levels of gonadotropins, their common alpha-subunit and free testosterone, and discrepancy between immunological and biological activities of circulating follicle-stimulating hormone. AB - The recent availability of both cordocentesis, a low risk and effective technique for fetal blood sampling, and ultrasensitive/highly specific two-site immunofluorometric assays (IFMA) for pituitary and chorionic glycoprotein hormone (I-LH, I-FSH, and I-CG) measurement prompted us to study the maturation of hypothalamic-pituitary-gonadal function in 114 normal human fetuses (49 females and 65 males) from 17-40 weeks gestation. The subjects were selected from 216 consecutive cordocenteses carried out for rapid karyotyping and diagnosis of fetal infection or hematological disorders. In addition, FSH bioactivity (B-FSH) was measured by rat Sertoli cell aromatase induction assay, glycoprotein hormone alpha-subunit (alpha-SU) by RIA, and circulating free testosterone (fT) by direct analog technique. No significant cross-reactions were recorded in the different measurement methods. In particular, alpha-SU did not interfere in any IFMA, and CG cross-reactivity in LH IFMA was 0.5%. Circulating I-LH, I-FSH, and B-FSH levels at 17-24 weeks gestation were significantly higher in female than in male fetuses (I-LH, 48 +/- 4 vs. 6.3 +/- 0.7 U/L; I-FSH, 35 +/- 2 vs. 0.7 +/- 0.1 U/L; B-FSH, 131 +/- 17 vs. 43.4 +/- 5.4 U/L). During the last weeks of gestation, a significant decrease in I-LH and I-FSH levels was seen in both female and male fetuses (I-LH, 0.24 +/- 0.05 and 1.0 +/- 0.3 U/L; I-FSH, 0.45 +/- 0.1 and 0.5 +/- 0.1 U/L), while serum B-FSH remained elevated, but the previously recorded difference between sexes disappeared (54.3 +/- 7.2 and 58.7 +/- 7.3 U/L). Circulating I-CG and alpha-SU levels at midgestation were elevated in both female and male fetuses (I-CG, 117 +/- 29 and 191 +/- 44 U/L; alpha-SU, 143 +/- 16 and 105 +/- 9 micrograms/L, respectively) and decreased thereafter (I-CG, 42 +/- 9 and 26 +/- 6 U/L; alpha-SU, 60 +/- 15 and 37 +/- 6 micrograms/L). Serum fT levels at midgestation were significantly lower in females than in males (4.3 +/- 0.9 vs. 10.0 +/- 0.8 pmol/L) and increased until term, when the difference between sexes disappeared (16.2 +/- 1.8 vs. 17.6 +/- 1.6 pmol/L).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1908480 TI - Analysis of the copulsatility of anterior pituitary hormones. AB - We have used combinatorial algebra and computer simulations to calculate expected means, variances, and probabilities of hormone-peak coincidences in 2 or more endocrine pulse series. We illustrate application of this conditional probability analysis to pulsatile LH, FSH, and/or PRL data. We observed that 1) serum LH and FSH pulses in 14 young men were randomly associated on different days (P greater than 0.10), but highly synchronized on any given day (P less than 0.0001); 2) serum LH and FSH (P less than 0.0001), LH and PRL (P = 0.023), and FSH and PRL (P = 0.0003) peaks were significantly coupled in healthy postmenopausal women; and 3) the number of triple coincidences among LH, FSH, and PRL release episodes in postmenopausal women significantly exceeded chance expectations (P less than 0.0001). We conclude that suitable statistical coincidence analysis can offer an informative tool with which to evaluate nonrandom event concordance in endocrine investigations, such as clinical studies of the temporally coordinated release of anterior pituitary hormones. PMID- 1908481 TI - Titrating luteinizing hormone surge requirements for ovulatory changes in primate follicles. I. Oocyte maturation and corpus luteum function. AB - The amplitude and duration of the midcycle LH surge required for ovulatory maturation of the follicle and its enclosed oocyte in primates are unknown. To titrate periovulatory LH requirements, female rhesus monkeys received human gonadotropins (FSH with/without LH) for 9 days beginning at menses to promote the development of multiple preovulatory follicles. The next day, animals (n = 4 6/group) received: 1) no ovulatory stimulus; 2) 1000 IU hCG, im; 3) one injection of 100 micrograms GnRH, sc (GnRH-1); 4) three injections of GnRH (GnRH-3) at 3-h intervals (0800, 1100, and 1400 h); or 5) two injections of 50 micrograms GnRH agonist (GnRHa), sc, 8 h apart (0800 and 1700 h) to induce ovulatory maturation. Follicles were aspirated 27 h after the hCG or initial GnRH/GnRHa injection or on days 8 and 10 in animals receiving no ovulatory stimulus. Nuclear maturity of oocytes was evaluated as a marker for reinitiation of meiosis. Estradiol and progesterone levels were determined in daily serum samples by RIA. Levels of LH( like) bioactivity were measured at selected intervals after hCG injection and within 24 h of GnRH/GnRHa treatment. In all groups, estradiol continuously rose to similar peak levels on day 10. The hCG treatment markedly elevated circulating LH-like bioactivity for up to 3 days. In GnRH-1, bioactive LH increased to 433.1 +/- 170.2 ng/mL (mean +/- SEM; n = 3) within 1-2 h, but then decreased to baseline (4.9 +/- 1.5 ng/mL) within 6 h. GnRH-3 and GnRHa treatment extended the interval of elevated bioactive LH to 8 and 14 h, respectively. There was no difference in the peak levels of LH(-like) bioactivity reached after hCG, GnRH, or GnRHa injection. Functional luteal phases were absent in monkeys receiving no ovulatory stimulus, whereas hCG treatment increased progesterone levels to 101 +/ 9 nmol/L (n = 6) and elicited functional luteal phases of 11.8 +/- 0.4 days. In contrast, only one animal in the GnRH/GnRHa groups (i.e. one GnRH-3 monkey) displayed elevated progesterone levels in the luteal phase. Of the total cohort of oocytes aspirated from follicles, a greater (P less than 0.05) proportion were classified as being in metaphase I or II of meiosis after hCG treatment (86%) compared to no ovulatory stimulus (13%), GnRH-1 (0%), GnRH-3 (43%), and GnRHa (12%). Thus, GnRH elicits a transient LH surge that can be extended by GnRH-3 or GnRHa in stimulated cycles of monkeys.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1908482 TI - Titrating luteinizing hormone surge requirements for ovulatory changes in primate follicles. II. Progesterone receptor expression in luteinizing granulosa cells. AB - The events in granulosa cells that are initiated by the midcycle LH surge during luteinization of the primate follicle are poorly defined. This study was designed 1) to determine whether an ovulatory dose of hCG can induce progesterone receptors (PR) in macaque granulosa cells, and if so, 2) to begin titrating gonadotropin requirements for PR expression and progesterone production by luteinizing granulosa cells. Rhesus monkeys were treated with human FSH and LH for up to 9 days to stimulate the growth of multiple follicles. The next day, animals (n = 4-5/group) received: 1) no ovulatory stimulus; 2) 1000 IU hCG, im; 3) one injection of 100 micrograms GnRH, sc (GnRH-1); 4) three injections of GnRH (GnRH-3) at 3-h intervals (0800, 1100, and 1400 h); or 5) two injections of 50 micrograms GnRH agonist (GnRHa), sc, 8 h apart (0800 and 1700 h). Granulosa cells obtained by follicle aspiration 27 h after the hCG or initial GnRH/GnRHa injection or on days 8 or 10 from animals receiving no ovulatory stimulus were processed for indirect immunocytochemistry using a monoclonal antibody to human PR (JZB39). Specific staining for PR, determined by comparing cells incubated with PR antibody vs. a nonspecific antibody, was undetectable in granulosa cells from monkeys without an ovulatory stimulus. In contrast, the majority (64 +/- 5%) of cells from hCG-treated animals stained intensely for PR. In the GnRH/GnRHa groups, granulosa cells from only one animal (i.e. one GnRH-3 monkey) showed positive staining for PR. During 24-h culture in Ham's F-10 medium containing 10% monkey serum, basal progesterone production by cells from the hCG-treated group (2163 nmol/L.8 x 10(4) cells) was higher than that by cells from the no ovulatory stimulus/GnRH-1/GnRH-3/GnRHa groups (60, 111, 194, and 332 nmol/L, respectively). However, granulosa cells from the hCG-treated group were less responsive to hCG in vitro in terms of enhanced progesterone production (2 times control levels) than cells from the other four groups (up to 30 times control levels). This study provides direct evidence that an ovulatory dose of hCG induces PR expression in granulosa cells of luteinizing follicles during stimulated cycles in rhesus monkeys. However, repeated injections of GnRH/GnRHa that produced surge levels (greater than 100 ng/mL) of endogenous LH for up to 14 h failed to induce PR expression or progesterone production by granulosa cells. Thus, an extended LH surge more typical of that in the normal menstrual cycle (48-50 h) may be necessary for PR expression and luteinization of granulosa cells in primate follicles. PMID- 1908483 TI - Localized irradiation of testes with carcinoma in situ: effects on Leydig cell function and eradication of malignant germ cells in 20 patients. AB - Twenty men (median age, 31 yr) previously treated for unilateral testicular cancer received localized irradiation in a dose of 20 Gray in 10 fractions for carcinoma in situ of the remaining testis. Follow-up testicular biopsies performed 3 (n = 19) and 24 (n = 14) months after the treatment showed in all cases a Sertoli cell-only pattern. Hormonal evaluation was performed before as well as 3, 12, 24, and 36 months after radiation treatment. Endocrine parameters were followed for a median of 30 months (3-36 months). Baseline serum testosterone values decreased during the follow-up period from 13.3 +/- 6.0 to 10.8 +/- 6.4 nmol/L (mean +/- SD), although the decrease was not statistically significant (P = 0.06). Serum LH values increased during the first 3 months of follow-up from 10.4 +/- 5.4 to 15.6 +/- 7.3 IU/L (P less than 0.0001) and then remained unchanged. Significant decreases in GnRH- and hCG-stimulated testosterone levels also indicated an impairment of Leydig cell function. FSH levels increased (P less than 0.0001) during the first 3 months of follow-up from 21.8 +/- 11.1 to 33.2 +/- 13.2 IU/L. We conclude that localized irradiation of 20 Gray eradicated carcinoma in situ germ cells. Development of a second testicular cancer has until now been prevented. Leydig cell function was partially impaired by the radiation dose given. PMID- 1908484 TI - Sex steroid control of gonadotropin secretion in the human male. I. Effects of testosterone administration in normal and gonadotropin-releasing hormone deficient men. AB - The precise sites of action of the negative feed-back effects of gonadal steroids in men remain unclear. To determine whether testosterone (T) administration can suppress gonadotropin secretion directly at the level of the pituitary, the pituitary responses to physiological doses of GnRH were assessed in six men with complete GnRH deficiency, whose pituitary-gonadal function had been normalized with long term pulsatile GnRH delivery, before and during a 4-day continuous T infusion (15 mg/day). Their responses were compared with the effects of identical T infusions on spontaneous gonadotropin secretion and the response to a 100 micrograms GnRH bolus in six normal men. Both groups were monitored with 15 h of frequent blood sampling before and during the last day of the T infusion. In the GnRH-deficient men, the first three GnRH doses were identical and were chosen to produce LH pulses with amplitudes in the midphysiological range of our normal men (i.e. a physiological dose), while the last four doses spanned 1.5 log orders (7.5, 25, 75, and 250 ng/kg). The 250 ng/kg dose was always administered last because it is known to be pharmacological. In the GnRH-deficient men, mean LH (P less than 0.02) and FSH (P less than 0.01) levels as well as LH pulse amplitude (P less than 0.05) decreased significantly during T infusion, demonstrating a direct pituitary-suppressive effect of T and/or its metabolites. Mean LH levels were suppressed to a greater extent in the normal than in the GnRH-deficient men (58 +/- 15% vs. 28 +/- 7%; P less than 0.05). In addition, LH frequency decreased significantly (P less than 0.01) during T administration in the normal men. These latter two findings suggest that T administration also suppresses hypothalamic GnRH release. T was unable to suppress gonadotropin secretion in one GnRH deficient and one normal man. In both groups, the suppressive effect of T administration was present only in response to physiological doses of GnRH. Because the pituitary- and hypothalamus-suppressive effects of T could be mediated by its aromatization to estrogens, five GnRH-deficient and five normal men underwent identical T infusions with concomitant administration of the aromatase inhibitor testolactone (TL; 500 mg, orally, every 6 h). As an additional control, four GnRH-deficient and four normal men received TL alone. TL administration completely prevented the effect of T administration to suppress gonadotropin secretion in both the normal and GnRH-deficient men, and mean LH levels increased significantly in both the GnRH-deficient (P less than 0.01) and the normal (P less than 0.001) men who received TL alone. The increase in mean LH levels was greater (P less than 0.01) in the normal men who received TL alone than in the normal men who received T plus TL, thus revealing a direct effect of androgens in normal men. Measurements of T and estradiol production rates in three men demonstrated that TL effectively blocked aromatization.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1908485 TI - Sex steroid control of gonadotropin secretion in the human male. II. Effects of estradiol administration in normal and gonadotropin-releasing hormone-deficient men. AB - Although prior studies have suggested that estrogens exert their negative feedback effect at the pituitary level in men, these conclusions have been based on models that evaluate changes in LH pulse amplitude and frequency and, therefore, only provide indirect information concerning the site of action of estrogens. To assess whether estradiol (E2) inhibits gonadotropin secretion directly and solely at the pituitary level in men, we determined the pituitary responses to physiological doses of GnRH in six men with complete GnRH deficiency, whose pituitary-gonadal function had been normalized with long term pulsatile GnRH delivery, before and during a 4-day continuous E2 infusion (90 micrograms/day). To deduce whether E2 has an additional inhibitory effect on hypothalamic GnRH secretion, their responses were compared with the effects of identical E2 infusions on spontaneous gonadotropin secretion and the responses to a 100-micrograms GnRH bolus in six normal men. Both groups were monitored with 15 h of frequent blood sampling before and during the last day of the E2 infusion. In the GnRH-deficient men, the first three GnRH doses were identical and chosen to produce LH pulses with amplitudes in the midphysiological range of values in our normal men (i.e. a physiological dose), while the last four doses spanned 1.5 log orders (7.5, 25, 75, and 250 ng/kg). The 250-ng/kg dose was always administered last because it is known to be pharmacological. In the GnRH deficient men, mean LH and FSH levels as well as LH pulse amplitude all decreased significantly (P less than 0.02) during E2 infusion, demonstrating a direct pituitary-suppressive effect of E2. Mean LH (P less than 0.01) and FSH (P less than 0.05) levels and LH pulse amplitude (P less than 0.01) also decreased significantly in the normal men. The degree of suppression of mean LH (52 +/- 3% vs. 42 +/- 12%) and FSH (49 +/- 10% vs. 37 +/- 10%) levels was similar in the two groups. These results provide direct evidence that E2 inhibits gonadotropin secretion at the pituitary level in men and suggest that the pituitary is the most important, and possibly the sole, site of negative feedback of estrogens in men. PMID- 1908486 TI - Follicular arrest during the midfollicular phase of the menstrual cycle: a gonadotropin-releasing hormone antagonist imposed follicular-follicular transition. AB - The functional dependency of the dominant follicle on pulsatile gonadotropin inputs was evaluated by using a GnRH antagonist as a probe. Hormonal dynamics, particularly the relationship of FSH, estradiol, and inhibin, during and after the withdrawal of GnRH receptor blockade achieved by treatment with Nal-Glu GnRH antagonist (50 micrograms/kg, im) for 3 days in the midfollicular phase of the cycle (days 7-9) were ascertained. Daily blood samples were obtained for LH, FSH, estradiol (E2), progesterone, and immunoreactive inhibin (i-INH) measurements by RIA during 2 consecutive (control and treatment) cycles in 12 women. In 5 women, LH pulsatility was assessed by 10-min blood sampling for 12 h before, during, and after Nal-Glu treatment. The administration of Nal-Glu prolonged both follicular phase (14.0 +/- 0.5 vs. 19.7 +/- 0.8 days; P less than 0.0001) and total cycle length (28.1 +/- 0.5 vs. 34.1 +/- 1.2 days; P less than 0.0001). Gonadotropin suppression (50-60%) was achieved, as reflected by a marked decrease in mean LH levels (14.3 +/- 1.9 to 5.4 +/- 0.5; P less than 0.01) and LH pulse amplitude (5.5 +/- 0.7 to 2.4 +/- 0.3 IU/L; P less than 0.01) in response to Nal-Glu antagonist. The number of LH pulses was reduced (36%), but pulses remained discernible. Concentrations of FSH (10.8 +/- 1.4 to 5.9 +/- 0.4 IU/L; P less than 0.05), E2 (322.7 +/- 71.9 to 84.8 +/- 7.7 pmol/L; P less than 0.01) and i-INH (284.0 +/- 25.9 to 164.4 +/- 7.5 U/L; P less than 0.01) decreased concomitantly. Within 24-48 h of the last injection of Nal-Glu, all hormones had returned to pretreatment levels. This was followed by normal functional expression of follicular growth and maturation, as reflected by an increase in E2 and i-INH levels, timely ovulation, and normal luteal function. These findings indicate that an approximately 50% decline in gonadotropin support to the dominant follicle leads to functional arrest, but not demise, of the developing follicle(s) without triggering new folliculogenesis. The follicular apparatus retained its ability to reinitiate its original functionality once appropriate gonadotropin inputs were reinstated. PMID- 1908487 TI - The source of inhibin secretion during the human menstrual cycle. AB - The source of inhibin secretion during the human menstrual cycle was investigated in two ways. The concentration of inhibin was compared in samples obtained from the ovarian and peripheral veins of 41 women undergoing hysterectomy. In 13 of the women, the corpus luteum was enucleated at operation and the peripheral concentration of inhibin measured at intervals for 24 h. Inhibin was assayed by a heterologous RIA using an antiserum raised against 31 kilodalton bovine inhibin. The concentrations of estradiol and progesterone in the peripheral and ovarian veins were similar to those previously reported. During the early follicular phase, the geometric mean inhibin concentrations were found to be significantly higher in both the right and left ovarian veins than the peripheral vein (180.4 and 157.7 vs. 78.7 U/L: P less than 0.02) but no difference was found in the late follicular phase between the vein draining the dominant ovary and the contralateral ovarian vein (231.1 vs. 193.4 U/L: NS). The inhibin concentrations in the veins draining the ovary bearing a corpus luteum were, however, significantly higher than those in the contralateral ovarian veins during the mid (409.1 vs. 203.6 U/L: P less than 0.02) and late (287.1 vs. 153.2 U/L: P less than 0.01) luteal phases. After enucleation of the corpus luteum, the inhibin concentration fell from the level seen before lutectomy (134.4 U/L) to 80.0 U/L at 24 h (P less than 0.01). This study demonstrates conclusively that the human corpus luteum secretes inhibin. No increase in inhibin secretion was seen from the dominant follicle in the late follicular phase. This casts doubt on the hypothesis that the selective suppression of FSH during the follicular phase is due to inhibin from the dominant follicle. PMID- 1908488 TI - Establishing pregnancies after follicular stimulation for IVF with clomiphene citrate and human menopausal gonadotrophin only. AB - Data are presented on establishing pregnancies by IVF during 1987 using only clomiphene citrate and human menopausal gonadotrophin for follicular stimulation. Of the 562 patients undergoing follicular stimulation, 80% reached oocyte recovery and 70% had at least one conceptus replaced. Patients having one or more (up to a maximum of four) conceptuses replaced demonstrated a significant increase in the establishment of pregnancies from one to two (14-29%: P = 0.035) and from two to three conceptuses (29-42%: P = 0.037). There was a significant decline in pregnancies when four conceptuses were replaced compared with three (P = 0.004). The data were also analysed according to the cause of infertility, specifically tubal, endometriosis, unexplained infertility and male factors only. After the replacement of conceptuses, the incidence of implantation and abortion was not significantly different. The incidence of pregnancy declined significantly after 35 years (26%) compared with women under 31 years (43%; P = 0.043). Of 129 women having three conceptuses replaced, in those greater than 35 years (63 patients) 23 (37%) became pregnant whereas in those less than 31 years (65 patients), 34 (52%; P = 0.05) became pregnant. Twenty-two per cent of stimulated cycles resulted in an endogenous LH surge and the incidence of patients having three conceptuses replaced in this group was lower than those in the HCG group (P = 0.007). Fertilization per oocyte was also significantly reduced (P less than 0.001) in patients with an LH surge. In total, 2824 oocytes were recovered and 57% fertilized with 54% of patients having three conceptuses replaced.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1908489 TI - Studies on the influence of gonadotrophin levels in the early follicular phase on the ovarian response to stimulation. AB - The gonadotrophic regulation of folliculogenesis has been extensively investigated but little attention has been paid to the influence of early follicular phase levels of endogenous FSH and the FSH/LH ratio when planning ovulation stimulation therapy for IVF. The influence of these factors was investigated in the three studies reported in this paper. A fixed schedule of ovulation stimulation therapy which employed standard treatment regimens, irrespective of the ovarian response, was used to eliminate variation due to treatment factors. Cycles were pretreated with an oestrogen-progestogen contraceptive pill or a progestogen (norethisterone). It was found that both oestrogen-progestogen and progestogen alone decreased the plasma FSH level, although the FSH/LH ratio was significantly reduced only by oestrogen progestogens. In clinical IVF studies, oestrogen-progestogen pretreatment was associated with a significant reduction in the preovulatory concentration of oestradiol in plasma and the number of aspirated follicles, compared to norethisterone. The administration of FSH for 2 days following oestrogen progestogen pretreatment and prior to the fixed schedule of ovulation stimulation normalized ovarian steroidogenesis and follicular development. Early follicular phase supplementation with FSH had no influence on progestogen pretreated cycles. The final experiment investigated the influence of FSH/LH levels in the early follicular phase on the outcome of ovarian stimulation. The preovulatory oestradiol concentration was reduced when baseline FSH/LH levels were low compared with when these values were high. Administration of FSH for 2 days in the early follicular phase improved the preovulatory level of oestradiol when baseline FSH/LH was low but had no effect when baseline FSH/LH levels were high.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1908490 TI - Interferon-gamma secretion by in vivo activated cytotoxic T lymphocytes from the blood and cerebrospinal fluid during mumps meningitis. AB - Functional studies of cerebrospinal fluid T lymphocytes during acute viral infections of the nervous system are rare. Recently, we had the opportunity to investigate the requirements for interferon-gamma (IFN-gamma) production of human in vivo activated (primary) cytotoxic T lymphocytes (CTL) generated during acute viral meningitis. Two HLA-B7-restricted, CD4-, CD8+ CTL clones from cerebrospinal fluid of one patient with mumps meningitis were studied. Although lytic activity was restricted by HLA-B7, the clones produced similar amounts of IFN-gamma when stimulated with HLA-matched and mismatched mumps virus-infected target cells. In addition, peripheral blood mononuclear cells of infected patients secreted significant amounts of IFN-gamma when incubated with autologous or allogeneic (HLA-A/B-mismatched) mumps virus-infected target cells. T cells capable of lytic activity and IFN-gamma secretion could only be isolated from venous blood during the initial phase of the infection. We suggest that the ability of human in vivo activated CTL to secrete INF-gamma early during the course of inflammation and in a HLA-unrestricted fashion is important for the elimination of viruses invading the central nervous system. PMID- 1908491 TI - Carbonic anhydrase II expression in fibrous astrocytes of the sheep. AB - Immunohistochemical expression of carbonic anhydrase isoenzyme II (CAII) was demonstrated in a population of fibrous astrocytes in a young lamb and an adult sheep. Such cells were identified by co-expression of CAII and glial fibrillary acidic protein, nuclear morphology and their contribution of glial fibrillary acidic protein reactive processes to the glial limitans. Similar cells were not identified in neonatal lambs. As in man and mouse, CAII was also expressed in choroid plexus epithelium occurring in neonate, young and adult sheep brain. In contrast, however, to man and mouse, CAII was not expressed in sheep oligodendrocytes. PMID- 1908492 TI - Prognostic signs in the evolution of premature thelarche by discriminant analysis. AB - Since premature thelarche (PT) can be a first sign of precocious puberty (PP), the aim of our study was to identify simple items in the course of the first 6 months of follow-up that could help predict if PT would evolve to PP. Thirty-two girls with PT were studied. First evaluation included bone age (BA), basal estradiol, FSH, LH and prolactin. GnRH was performed in 15 subjects and BA was checked at 6 month intervals in 30. Based on clinical outcome after a mean follow up of 33.4 +/- 16.5 (SD) months, patients were divided into 2 groups: Group I (G I) included subjects whose breast development either remained unchanged, increased or regressed; Group II (G-II) included subjects who progressed to PP. The multivariate combination of the items which was able to best discriminate between the two groups was chosen in predicting the evolution of PT. The items considered included four variables available at the time of diagnosis [chronological (CA) at onset less than 3 years, basal FSH, basal LH and BA/CA ratio] and two additional variables after a 6-month follow-up (delta BA/delta CA and growth velocity); 88% of G-I and 14% of G-II had CA less than 3 yr. Basal FSH levels were elevated in both G-I (7.6 +/- 3.0 mIU/ml) and G-II (12.1 +/- 4.1) with respect to controls (2.6 +/- 1.2); however, approximately 20% of G-I had low FSH levels. Basal LH levels were consistently higher in G-II (8.0 +/- 1.3 mIU/ml) than in G-I (2.9 +/- 1.5) or controls (2.8 +/- 1.2). Although initial BA was advanced (greater than 2SD) in 21% of G-I and in all of G-II, an acceleration of BA was seen only in G-II. The mean growth velocity of G-I (44.1 +/- 31.5%) was significantly less than G-II (92 +/- 32%; p less than 0.0025). With the help of the discriminant equations derived from data obtained at diagnosis and during the first 6 months of follow-up, all subjects with isolated premature thelarche could be sharply distinguished from those who subsequently progressed to precocious puberty.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1908494 TI - Regulation of breathing at birth. AB - The factors which regulate the transition to lung gas exchange in the newborn are not well understood. The transition begins within seconds of birth with the newborn's first breath and is largely complete by 30 min of age at which time breathing is continuous, and arterial blood gas tensions and pH approach stable newborn values. Experiments indicate that sensory stimulation caused by cutaneous cooling or sciatic nerve stimulation can result in the initiation of breathing within seconds. Thus, massive sensory stimulation of the newborn caused by labour and delivery probably plays an important role in promoting the rapid onset of lung ventilation. Any delay in the onset of lung gas exchange causes a rise in arterial PCO2 and fall in pH which would stimulate breathing probably via stimulation of the central chemoreceptors. Since an impairment of CO2 elimination is usually observed after birth, a rise in arterial PCO2 likely stimulates breathing in the newborn. However, this impairment is transient and is usually corrected within 30 min to 2 h of age. Recent experiments suggest that placental perfusion inhibits the fetal central respiratory system and that this effect may be mediated by a placentally-produced respiratory inhibitor. Thus, withdrawal of a respiratory inhibitor from the circulation may play an important role in maintaining breathing in the newborn after sensory stimulation wanes and arterial PCO2 returns to normal fetal levels. PMID- 1908493 TI - Altered growth hormone response after growth hormone releasing hormone administration in chronic renal failure. AB - Eleven chronic renal failure patients and 11 matched controls, received growth hormone GHRH (1 microgram/kg iv) or TRH (400 microgram iv) on separate occasions, immediately before undergoing hemodialysis. GHRH-induced GH peak in uremics (22.7 +/- 5.2 micrograms/l) was not different from that obtained in control subjects (16.0 +/- 4.3 micrograms/l). However, the uremic patients did not show the habitual post-peak fall, remaining GH levels over 10 micrograms/l till the end of the test. Differences between the two groups were significant (p less than 0.05). Uremic patients showed PRL values higher than in controls, however their TRH induced PRL peak (20.6 +/- 6.6 micrograms/l) was not different from that of controls (26.5 +/- 3.0 micrograms/l). Again chronic renal failure patients showed PRL plasma values abnormally elevated till the end of the test. Differences between the two groups were significant (p less than 0.05). Administration of placebo to a different group of seven uremic patients did not alter GH and PRL plasma levels. This sustained secretion of both GH and PRL in uremia could be attributed to reduced kidney clearance. However, when subjects were examined individually both the GHRH- and the TRH-induced hormonal peaks and the subsequent fall were not different in both groups. Unlike with controls, in uremic patients GHRH-stimulated GH and TRH-stimulated PRL/GH peaks were dispersed throughout the 120 min period. In controls GH and PRL peaks clustered around 15-30 min. The peak dispersion created a false impression of flattened curves or sustained hypersecretion in uremia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1908495 TI - Immunization against Schistosoma mansoni by using Trichinella spiralis and Trichinella pseudospiralis antigens. AB - The antigenic fraction of a cell free homogenate of each of Trichinella spiralis and T. pseudospiralis were prepared to be used for induction of immunity against S. mansoni in albino mice. The results of the study showed that immunization with either of the two antigens induced reduction in worm load ranging from 80.48% to 87.86% in the different groups of the study. Reduction in tissue egg count was also reported: Liver egg count was reduced from 69.47% to 100%. Intestinal egg count reduction ranged from 73.83% to 99.78%. There was also reduction in egg excretion as evidenced by diminution in stool egg count. Liver granulomas were less in number and size and showed accelerated reaction together with inhibition of fluorescence. These findings were more manifest in animals given T. spiralis than T. pseudospiralis antigen. PMID- 1908496 TI - Endodyogony and cyst formation of Sarcocystis gongyli (Trinci 1911) from the skink Chalcides ocellatus. AB - The heteroxenous life cycle of S. gongyli comprising both the skink Chalcides ocellatus (intermediate host) and the snake Spalerosophis diadema, herewith the process of cyst formation was followed by means of light and electron microscopy after experimental infection. Following migration of the merozoites to muscle fibres, they changed into globular metrocytes, meanwhile a parasitophorous vacuole enclosing them. As development proceeded the wall of the parasitophorous vacuole is thickened in the form of striated protrusions as well as the metrocytes underwent endodyogony producing large numbers of banana-shaped merozoites in the centre of the cyst. Mature microscopic sarcocyst appeared at 120 days p.i, and these were characterized by presence of stalky leaf-like protrusions in their primary cyst wall. Asexual multiplication of metrocytes occurred through endodyogony in which always the mother metrocyte produced two opposite merozoites. PMID- 1908497 TI - Ecto and endoparasites in two primary schools in Qualyob City, Egypt. AB - Ecto and endoparasites are still one of the public health problems in Egypt. This is particularly true among school students who are exposed to the parasitic infections or infestations by autoinfection or by contagious. In this paper, two primary schools were selected in Qualyob City, Qualyobia Governorate (in the Nile Delta). Examination of 486 school children (6-12 years old) revealed pediculosis (16.04), schistosomiasis (8.8%), amoebiasis (7.81%), giardiasis (9.05%), taeniasis saginata (0.41%), ascariasis (9.05%), enterobiasis (0.9%) and hymenolepiasis nana (9.87%). It was found that ectoparasites (lice) represented 17.8% of the total parasites detected in the children. Endoparasites transmitted by autoinfection represented 43.02%, those transmitted by skin penetration represented 9.84%, those transmitted by meat consumption represented 0.45% and by other modes of infection represented 28.8%. It was concluded that school children are the group of individuals at risk. They spend long time outside their homes in a crowd area. Besides, they convey the parasites, particularly those transmitted by contagious and autoinfection to their family members. PMID- 1908498 TI - Study of some aspects of cell mediated immune response in bilharzial children on a field level. AB - S. mansoni patients with active intestinal mansoniasis with or without hepatosplenomegaly were divided into 3 groups. The first was treated by praziquantel therapeutic course, second by an initial full dose of praziquantel to be followed by suppressive doses, and third received initial loading praziquantel dose and followed by the suppressive dose at monthly intervals. School children infected with S. haematobium were divided into 5 groups: The first received oral metrifonate therapeutic course followed by its prophylactic course monthly, second with full dose of oral praziquantel, third with metrifonate orally every month, fourth half dose of praziquantel orally every month, fifth received oral metrifonate curative course every 2 weeks for 3 doses every 6 months, repetition of such therapy was carried out 6 monthly for non cured cases. Non-bilharzial children were studied and divided into six groups. The first was given an oral monthly praziquantel prophylactic dose. The second received the same prophylactic praziquantel doses given at 3-monthly intervals. The third was given an oral placebo in the form of vitamin B complex tablets at 3 monthly intervals. The fourth received oral monthly therapeutic dose of metrifonate. The fifth was given oral monthly prophylactic doses of praziquantel. The sixth was given oral placebo in the form of 2 vitamin B-complex tablets monthly. For every individual whole blood leucocyte % phagocytosis and tuberculin test were performed. In cases infected with S. mansoni the mean percent phagocytosis was only markedly reduced in hepatosplenic cases of groups P-1, P-2 and P-3 during praziquantel treatment. Tuberculin reactivity was not changed following such therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1908499 TI - Histochemical studies on rectal mucosa in active intestinal schistosomiasis. AB - Thirty patients suffering from active intestinal S. mansoni infection, were classified into 3 groups. The first group: 13 cases with early active intestinal schistosomiasis without hepatosplenomegaly. The second group: 11 cases with hepatosplenomegaly and the third group: 6 cases with splenomegaly and ascites. Also 10 normal individuals were included as a normal control group. Histopathological examination of rectal mucosa showed hyperaemia with extravasation of blood in early cases and granulomatous lesions in the second group with hepatosplenomegaly. The structural changes were severe in the late ascitic group. In this group the rectal mucosal glands showed distorted irregular tubular branching in addition to the granulomatous and the fibrous reactions. Histochemical studies including periodic acid schiff, alkaline phosphatase and acetyl cholinestrase reactions were done. Using the periodic acid shiff stain, the goblet cells showed strong reaction for neutral mucin in cases of group I (early cases) and group II (late hepatosplenomegalic cases). In group III (late ascitic cases) the goblet cells were faintly stained. A notable difference was observed between the lightly and heavily infected patients of this group. No alkaline phosphatase reactivity could be identified in rectal crypts of patients and controls. Alkaline phosphatase reactivity was sharply localised in S. mansoni egg shell. There was obvious decrease in the acetyl cholinesterase stained nerve fibres in the rectal mucosa of all studied patients. The decrease was more in chronic and heavily infected cases rather than in the acute and lightly infected ones. PMID- 1908500 TI - Schistosomiasis affection of the kidney as a possible cause of renal stone formation. AB - Nowadays, renal stone is one of the medical complaints. Many theories have been suggested to account for its formation. The present work aimed to find out a correlation between schistosomiasis affection of the kidney and the formation of renal stones. Three groups of patients with renal stones were selected. They had Schistosoma mansoni infection (1st group), with Schistosoma haematobuim infection (2nd group) and Schistosoma free (3rd group or control). The results showed pathological changes in the kidney biopsied materials, particularly the glomerulus, ranging from periglomerular fibrosis to complete atrophy and lymphoid follicles in the interstitium. Sometimes, distal-tubular atrophy was seen. The serum and tissue immunoglobulins, particularly the IgA, in schistosomiasis patients were above normal as compared to control ones. It is concluded that the schistosomiasis affection of the kidney, and the resulting immunopathological changes were factors predisposing, in one way or another, to the formation of renal stones. PMID- 1908501 TI - Estimation of serum and tissue immunoglobulins level in some colonic disorders. AB - The immunoglobulins level, were estimated in the sera of 51 patients with different colonic disorders and 12 controls. In 27 of them, tissue immunoglobulin level were estimated. In bilharzial patients there was significant increase in the serum level of IgG, IgM and IgE. IgA and IgD showed no change. IgA containing cells were (87.5%), IgG (50%) and IgM (16.7%). In patients with amoebic colitis, there was significant increase in serum IgG and IgE. IgA and IgD showed significant decrease while IgM was within normal limits. Tissue IgA and IgG were detected in all acses. IgM containing cells were detected in 2 cases. In patients with irritable bowel syndrome (I.B.S.), there was significant high levels of IgM and IgE. IgG showed significant low level, while IgG and IgA showed no change. Tissue IgA were detected in (70%), IgG in (10%) and IgM in (20%). In patients with ulcerative colitis (U.C.), there was significant high levels of IgM and IgE. IgD showed significant low level, while IgG and IgA showed no change. Tissue IgA, IgG and IgM were detected in all cases. In patients with Crohn's disease, the 3 immunoglobulins were detected. PMID- 1908502 TI - The role of rodents as reservoirs for some diseases in new reclaimed areas in north Sinai. AB - In a trial to determine the role of Sinai rodents as reservoirs to rickettsial diseases, the IFA technique was used to detect the presence of R. typhi and spotted fever group in blood of some commensal and wild rodent species collected in Sinai during the last five years (1985-1989). Out of 277 Rattus spp. collected in El Arish (47.3%) were positive to R. typhi and only (5.9%) of 35 Mus musculus were positive to R. typhi. As for Gerbillus spp. only (1.5%) of 206 animals were positive for R. typhi. The positive cases of spotted fever group were (34.6%) in Rattus spp. and (18.8%) in Gerbillus spp. PMID- 1908503 TI - Vaccine induced immunity to Schistosoma mansoni: spleen cell proliferative responses before and after challenge in BALB/c mice given irradiated or normal schistosomula. AB - Spleen cell proliferative responses in BALB/c mice were assessed at varying intervals after vaccination or primary infection and subsequent cercarial challenge. Mice were vaccinated with 500 50-Krad-irradiated Schistosoma mansoni schistosomula or infected with 20 normal schistosomula. Prior to challenge, splenic responses in the two test groups to phytohemagglutinin (PHA) declined progressively while schistosomula (SMA)-driven responses increased. After challenge, PHA responses increased in both groups on day 3 then declined to significantly lower levels compared to normal controls. On day 3 after challenge, SMA responses in vaccinated mice were vigorous, and greater than twice the responses in infected mice. Thereafter, responses in vaccinated mice declined while responses in infected mice increased on days 7 through 25 but dropped markedly by day 39. For the infected group, in vitro depletion of plastic adherent cells or Lyt 2.2+ lymphocytes resulted in augmented SMA responses 3 days post-challenge by greater than 400% and greater than 100%, respectively. Depletion of either cell population in the vaccinated group had no significant effect. Protection assessed by total worm burdens showed a reduction of 62% in vaccinated mice and 43% reduction in infected mice. The post-challenge results indicate that these two models of anti-schistosomula immunity differed in the dynamics of their splenocyte antigen-specific proliferative responses. These findings may contribute to an understanding of the mechanisms by which resistance to S. mansoni is induced. PMID- 1908504 TI - [Diagnosis and therapy of pneumonia caused by gram-negative bacillus including legionella]. PMID- 1908505 TI - Local curative treatment of rectal cancer by radiotherapy alone. PMID- 1908506 TI - Source of tubercle bacilli in cervical lymph nodes: a prospective study. AB - A prospective study searching for associated mycobacterial infection of the upper aerodigestive tract in patients with cervical tuberculous lymphadenitis (TBLN) was carried out. One hundred and thirteen patients with a clinical suspicion of cervical TBLN were included. All patients had a physical examination of the upper aerodigestive tract. Routine endoscopy and biopsy of the nasopharynx were performed. All of them had surgery to the cervical lymph node. Seventy-five patients had histologically confirmed cervical TBLN. Culture of the lymph node specimen showed Mycobacterium tuberculosis in 68 (90 per cent). In 45 (60 per cent) patients with cervical TBLN the primary foci of infection could not be found. Twenty-nine (39 per cent) had radiographic evidence of active or healed pulmonary tuberculosis. Sputum culture from two patients showed Mycobacterium tuberculosis. Five patients (six per cent) had tuberculous nasopharyngitis. In one of them (one per cent) the tuberculous nasopharyngitis was primary as no other evidence of mycobacterial infection was found. In the present study, mycobacterial infection of other parts of the upper aerodigestive tract was not found. PMID- 1908507 TI - The interaction between CD8+ cytotoxic T cells and Leishmania-infected macrophages. AB - Leishmania is resident within the macrophages of its vertebrate host. In any intramacrophage infection, where the pathogen is present in a form capable of mediating cell to cell transmission, the contribution of a cytotoxic T cell response to protective immunity is questionable. This study presents data from an in vitro model designed to elucidate the outcome of an interaction between CD8+, cytotoxic T cells and infected macrophages. Experiments were conducted with an H 2d-restricted, cytotoxic CD8+ T cell clone and Leishmania parasites present in mixed macrophage cultures, with the parasites confined to either histocompatible BALB/c macrophages, or incompatible CBA macrophages. Initial experiments indicated that the viability of Leishmania was unaffected by the lysis of its host macrophage by cytotoxic T cells. However, extended experiments showed that the parasites were killed between 24 and 72 h. The same results were obtained regardless of whether the parasites were resident in the target, BALB/c, macrophages or the bystander, CBA, macrophages. Addition of neutralizing, anti IFN-g antibody to the cultures ablated most of the leishmanicidal behavior, indicating that parasite death was attributable to macrophage activation, resulting from cytokine secretion from the T cells following the initial recognition event. PMID- 1908508 TI - The role of clonal selection in the pathogenesis of an autoreactive human B cell lymphoma. AB - To study the association of autoimmunity and human B cell neoplasia, we have established a model of a B cell lymphoma which expresses a pathogenic autoantibody of defined specificity. The Ig VH gene expressed in this neoplasm was analyzed longitudinally using clinical specimens taken from the splenic lymphoma (S) at diagnosis and from lymph node relapses 3 and 4 yr later (N3 and N4). Southern analysis and oligonucleotide hybridization experiments demonstrated that clonally related predominant and minor tumor cell populations were present in S at diagnosis, and that the minor population became the predominant population in the relapse specimens, N3 and N4. Although the Ig specificity and idiotype were the same at diagnosis and at both relapses, analysis of the expressed VH gene sequences showed 14 base changes between S and N3, and 2 further changes at N4. Little sequence heterogeneity was observed at each sampling time, indicating that the ongoing mutation frequency was low. The relevant germline precursor VH gene was determined from autologous germline DNA and compared to the expressed genes. Based on the pattern of shared and unshared mutations, we were able to establish the genealogic relationship of the germline VH gene and the expressed clonotypes of S, N3 and N4. Taken together, the findings from Southern blotting, oligonucleotide hybridization, and sequence analysis permit us to describe a molecular aspect of tumor progression, "clonotypic shift", wherein subpopulations of the malignant clone, marked by different V gene clonotypes, emerge and predominate at different time points in the evolution of the lymphoma. Furthermore, the sequential and nonrandom pattern of the VH mutations, correlated with the observed conservation of autospecificity and idiotype, implies that clonal selection may have influenced the pathogenesis of the lymphoma. PMID- 1908509 TI - Regulation of Trypanosoma cruzi infections in vitro and in vivo by transforming growth factor beta (TGF-beta). AB - The effects of transforming growth factor beta (TGF-beta) on interferon gamma mediated killing of the intracellular protozoan parasite Trypanosoma cruzi and on the course of T. cruzi infection in mice were investigated. Spleen cells from mice with acute T. cruzi infections were found to produce elevated levels of biologically active TGF-beta in vitro, and the possibility that TGF-beta may mediate certain aspects of T. cruzi infection was then addressed. When mouse peritoneal macrophages were treated with TGF-beta in vitro, the ability of IFN gamma to activate intracellular inhibition of the parasite was blocked. This occurred whether cells were treated with TGF-beta either before or after IFN gamma treatment. TGF-beta treatment also blocked the T. cruzi-inhibiting effects of IGN-gamma on human macrophages. Additionally, treatment of human macrophages with TGF-beta alone led to increased parasite replication in these cells. The effects of TGF-beta on T. cruzi infection in vivo were then investigated. Susceptible C57BL/6 mice developed higher parasitemias and died earlier when treated with TGF-beta during the course of infection. Resistant C57BL/6 x DBA/2 F1 mice treated with TGF-beta also had increased parasitemias, and 50% mortality, compared with no mortality in infected, saline-treated controls. A single dose of TGF-beta, given at the time of infection, was sufficient to significantly decrease resistance to infection in F1 mice and to exacerbate infection in susceptible C57BL/6 mice. Furthermore, a single injection of TGF-beta was sufficient to counter the in vivo protective effects of IFN-gamma. We conclude that TGF-beta, produced during acute T. cruzi infection in mice, is a potent inhibitor of the effects of macrophage activating cytokines in vivo and in vitro and may play a role in regulating infection. PMID- 1908510 TI - Antibodies that are specific for a single amino acid interchange in a protein epitope use structurally distinct variable regions. AB - We have analyzed how the immune system generates antibodies that are specific for analogues of an epitope on the influenza virus hemagglutinin (HA) that differ solely by the presence of Asp or Gly at amino acid 225. Most antibodies induced in response to HA(Asp225) use one of a few closely related variable (V) region structures that are encoded by characteristic VH/Vk gene segment combinations. Remarkably, none of these VH/Vk combinations was induced in response to HA(Gly225). Instead of modifying the HA(Asp225)-specific V regions by junctional variation or somatic mutation to recognize the altered epitope, new VH/Vk combinations were used. The expression of unique VH/Vk combinations appears to confer exquisite specificity to the selection of HA-specific B cells from the pre immune repertoire. PMID- 1908511 TI - Bacterial entry and intracellular processing of Neisseria gonorrhoeae in epithelial cells: immunomorphological evidence for alterations in the major outer membrane protein P.IB. AB - The fate of the major outer membrane protein of the gonococcus, P.IB, during the adherence, entry, and intracellular processing of the bacteria in infected epithelial cells was investigated using post-embedding immunoelectron microscopy. Various domains of the P.IB molecule were probed at different stages in the infection. These studies revealed that P.IB epitope exposure remained unaltered during the initial attachment of the bacteria to the host cells. In contrast, upon secondary attachment of the bacteria to the eukaryotic cells, apparent zones of adhesion were formed between the gonococci and the host cell membrane, which were characterized by loss of a defined P.IB epitope. These zones of adhesion with the altered P.IB immunoreactivity continued to exist and increased in number during cellular penetration, suggesting that they were essential to bacterial invasion into the eukaryotic cells. After bacterial entry, two classes of gonococci could be recognized; morphologically intact, P.IB-positive bacteria and disintegrated organisms that showed a change in, and, in a later stage, a complete loss of P.IB immunoreactivity. The intracellular alterations in the P.IB antigen could be prevented by treatment of the host cells with the lysosomotropic agent chloroquine. These observations point to a mechanism by which a subpopulation of intracellular gonococci can escape the epithelial cell defense by preventing or resisting exposure to host cell proteolytic activity. PMID- 1908512 TI - Cell-cell adhesion mediated by CD8 and human histocompatibility leukocyte antigen G, a nonclassical major histocompatibility complex class 1 molecule on cytotrophoblasts. AB - The lymphocyte differentiation marker CD8 acts as a coreceptor with the T cell receptor (TCR) during recognition of peptide presented by major histocompatibility complex (MHC) class I molecules. The functions of CD8 in the TCR complex are thought to be signaling through the association of CD8 with the protein tyrosine kinase p56lck and adhesion to MHC class I through the alpha 3 domain. While the ability of the CD8 alpha/alpha homodimer to bind to classical MHC class I molecules has been shown, it is unclear whether CD8 can also bind nonclassical molecules. Of particular interest is human histocompatibility leukocyte antigen (HLA)-G which is expressed on placental cytotrophoblast cells. These cells do not express HLA-A, -B and -C molecules. In this report, we demonstrate that CD8 can bind to HLA-G. It is possible, therefore, that a cell bearing CD8 may interact with HLA-G-expressing cells. PMID- 1908513 TI - Neutrophil-mediated dissolution of infected host cells as a defense strategy against a facultative intracellular bacterium. AB - The rate of growth of Listeria monocytogenes in the livers of mice infected intravenously with a lethal or sublethal inoculum of this facultative intracellular bacterium is greatly increased if neutrophils and other host cells are prevented from accumulating at foci of infection during the first 24 h by treatment with a monoclonal antibody (5C6) specific for the type 3 complement receptor of myelomonocytic cells. A histological examination of the livers of control mice showed that the accumulation of neutrophils at infectious foci resulted in the focal destruction of infected hepatocytes. In contrast, failure of neutrophils to accumulate at these sites in 5C6-treated mice allowed Listeria to multiply extensively in hepatocytes without destroying them. The results indicate that neutrophils play an important role in early defense against listeriosis in the liver by destroying infected hepatocytes, thereby reducing the opportunity for Listeria to multiply in permissive cells. In this way, neutrophils serve to break the chain of cell-to-cell spread of infection. PMID- 1908514 TI - Injection of inositol trisphosphorothioate into Limulus ventral photoreceptors causes oscillations of free cytosolic calcium. AB - Limulus ventral photoreceptors contain calcium stores sensitive to release by D myo-inositol 1,4,5 trisphosphate (InsP3) and a calcium-activated conductance that depolarizes the cell. Mechanisms that terminate the response to InsP3 were investigated using nonmetabolizable DL-myo-inositol 1,4,5 trisphosphorothioate (InsPS3). An injection of 1 mM InsPS3 into a photoreceptor's light-sensitive lobe caused an initial elevation of cytosolic free calcium ion concentration (Cai) and a depolarization lasting only 1-2 s. A period of densensitization followed, during which injections of InsPS3 were ineffective. As sensitivity recovered, oscillations of membrane potential began, continuing for many minutes with a frequency of 0.07-0.3 Hz. The activity of InsPS3 probably results from the D stereoisomer, since L-InsP3 was much less effective than InsP3. Injections of 1 mM InsP3 caused an initial depolarization and a period of densensitization similar to that caused by 1 mM InsPS3, but no sustained oscillations of membrane potential. The initial response to InsPS3 or InsP3 may therefore be terminated by densensitization, rather than by metabolism. Metabolism of InsP3 may prevent oscillations of membrane potential after sensitivity has recovered. The InsPS3 induced oscillations of membrane potential accompanied oscillations of Cai and were abolished by injection of ethyleneglycol-bis (beta-aminoethyl ether)-N,N' tetraacetic acid. Removal of extracellular calcium reduced the frequency of oscillation but not its amplitude. Under voltage clamp, oscillations of inward current were observed. These results indicate that periodic bursts of calcium release underly the oscillations of membrane potential. After each burst, the sensitivity of the cell to injected InsP3 was greatly reduced, recovering during the interburst interval. The oscillations may, therefore, result in part from a periodic variation in sensitivity to a constant concentration of InsPS3. Prior injection of calcium inhibited depolarization by InsPS3, suggesting that feedback inhibition of InsPS3-induced calcium release by elevated Cai may mediate desensitization between bursts and after injections of InsPS3. PMID- 1908515 TI - Some highlights of virus research in 1990. PMID- 1908516 TI - Molecular cloning and sequence analysis of the genome of chicken anaemia agent. AB - The replicative form (RF) DNA of chicken anaemia agent (CAA) was isolated and cloned into bacterial plasmids. After religation of the cloned CAA DNA and transfection into MDCC-MSB1 cells, the DNA could induce c.p.e. characteristic of that caused by CAA, and an antigen was produced which gave positive immunofluorescence when detected with an anti-CAA serum. Sanger sequencing of the 2298 bp genome revealed several open reading frames (ORFs); the major ORF encoded a polypeptide of 51.8K. In SDS-PAGE of CAA viral particles a 50K protein has been reported as the only detectable viral protein. The genomic region downstream of the major ORF had several predicted GC-rich inverted repeats, a poly(A) signal and four copies of an 18 bp repeat element. Database searches did not reveal any sequence with homology to the viral genomic DNA, nor to the amino acid sequence of any of the ORFs, apart from the N-terminal 40 amino acids of the major ORF which showed a limited similarity to the structure of protamines. PMID- 1908517 TI - The potato leafroll luteovirus 17K protein is a single-stranded nucleic acid binding protein. AB - The potato leafroll luteovirus protein of Mr 17K (pr17), which is encoded by an open reading frame on the 3' half of the viral genome, was expressed by using bacterial expression vector systems. Fusion proteins were obtained for the full length viral protein as well as its N-terminal acidic (GST/pr17N) and C-proximal (GST/pr17C) basic domains and used in nucleic acid-binding studies. Filter-bound as well as soluble pr17 bound to single-stranded RNA or DNA. The binding domain was shown to reside in the basic C-proximal part of the polypeptide, whereas the N-terminal acidic domain did not show any affinity for nucleic acid. These biochemical properties of pr17 together with its structural features suggest a regulatory role for this protein during virus replication. PMID- 1908518 TI - Cost-effective resuscitation education. AB - Resuscitation education, offered by the American Heart Association, recently has expanded to include three pediatric courses. Nurse educators face internal and external constraints as they attempt to secure funding for these new programs. The Pediatric Resuscitation Course described in this article offers an innovative approach to programming and facilitates funding through the use of an integrated curriculum teaching format. This format reduces program cost without sacrificing valuable resuscitation education. PMID- 1908519 TI - Documentation of blood for transfusion. PMID- 1908520 TI - Use of sperm viability and acrosomal status assays in combination with immunofluorescence technique to ascertain surface expression of sperm antigens. AB - Sperm antigens are being sought for the development of prototype contraceptive vaccines. For vaccine-induced antisperm antibodies to inhibit the function of viable sperm, target antigens must be expressed on the sperm surface before, during or after the acrosome reaction. The purpose of this study was to develop an approach to detect accurately surface binding of antibodies to viable acrosome intact or acrosome-reacted sperm, and to confirm sperm surface binding characteristics of a panel of antisperm monoclonal antibodies submitted to the World Health Organization Antifertility Vaccines Task Force. Monoclonal antibodies were tested using a combination of carboxyl-fluorescein diacetate (CoFDA) sperm viability, and rhodamine immunofluorescence assays to ascertain surface binding to viable membrane-intact human sperm, and, in parallel studies, with a combination of fluorescein isothiocyanate (FITC) conjugated Pisum sativum agglutinin (PSA) and rhodamine immunofluorescence assays to ascertain the acrosomal status of antibody-positive sperm. Only 14 out of 32 antibodies that were previously considered to be surface-reactive were confirmed to be positive with these methods. Five were positive on unfixed viable (CoFDA-labelled) fresh sperm in this study, and 9 different antibodies were positive on unfixed acrosome reacted sperm. We conclude that this multifaceted approach is more accurate and informative than previous techniques used for detection of sperm surface antigens such as radioimmunoassay, standard immunofluorescence, sperm agglutination assays and enzyme-linked immunosorbent assays, which can give false positive results due to the presence of contaminating non-sperm cells, insoluble seminal plasma material, or permeabilized non-viable sperm. Furthermore, the combination of assays employed in this study does not depend on sperm motility, as do the immunobead and sperm immobilization assays, and provides information about the acrosomal status of antibody-positive cells. PMID- 1908521 TI - Naphthosultam derivatives: a new class of potent and selective 5-HT2 antagonists. AB - A series of 2-(aminoalkyl)naphth[1,8-cd]isothiazole 1,1-dioxides was synthesized and examined in various receptor binding tests. Most compounds demonstrated high affinity for the 5-HT2 receptor with moderate to high selectivity. A member of this series, compound 24 (RP 62203), displays high 5-HT2 receptor affinity (Ki = 0.26 nM), which is respectively more than 100 and 1000 times higher than its affinity for alpha 1 (Ki = 38 nM) and D2 (Ki greater than 1000 nM) receptors. This compound is a potent orally effective and long lasting 5-HT2 antagonist in the mescaline-induced head-twitches test in mice and rats. PMID- 1908522 TI - Syntheses of tolrestat analogues containing additional substituents in the ring and their evaluation as aldose reductase inhibitors. Identification of potent, orally active 2-fluoro derivatives. AB - A series of aldose reductase inhibitors were prepared which were analogues of the potent, orally active inhibitor tolrestat (1). These compounds (5, 7, 9, and 10) have an extra substituent on one of the unoccupied positions on the naphthalene ring of 1. Primary amide prodrugs of several members from the series 5 and 7, namely 6 and 8, respectively, were also prepared. These compounds were evaluated in two in vitro systems: an isolated enzyme preparation from bovine lens to assess their intrinsic inhibitory activity and an isolated sciatic nerve assay to determine their ability to penetrate membranes of nerve tissue. These compounds were also evaluated in vivo as inhibitors of galactitol accumulation in the lens, sciatic nerve, and diaphragm of galactose-fed rats. In general, compounds in series 5, 7, 9, and 10 were potent inhibitors of bovine lens aldose reductase. 2 Halo-substituted analogues from the series 5, 7, and 9 exhibited high activity in the nerve of the 4-day-galactose-fed rat, and in several instances, the primary amide prodrug 8 enhanced the in vivo potency of the respective carboxylic acid 7. Two 2-fluoro-derivatives, 8a and 9a, had especially high activity in vivo and were chosen for additional studies. These compounds were found to be approximately equipotent to tolrestat in the sciatic nerve of the galactose-fed rat and the STZ rat, as judged by their ED50's in these assays. Although primary amide analogue 8a did not have intrinsic inhibitory activity toward aldose reductase, it was metabolized to an active form in vivo and also in vitro within the sciatic nerve. PMID- 1908524 TI - Environmental contaminants and the reproductive success of lake trout in the Great Lakes: an epidemiological approach. AB - Epidemiological criteria were used to examine the influence of environmental contamination on reproductive success of lake trout (Salvelinus namaycush) in the Laurentian Great Lakes. Most of the information was obtained from lake trout eggs collected in southeastern Lake Michigan and reared in the laboratory. Two separate end points that measure reproductive success--egg hatchability and fry survival--were used in the evaluation. Strong evidence for maternally derived polychlorinated biphenyls causing reduced egg hatchability were observed for the time order, strength of association, and coherence criteria. Equally strong evidence for organic environmental contaminants, also of maternal origin, causing a swim-up fry mortality syndrome were presented for the strength of association, specificity, replication, and coherence criteria. The epidemiological approach for demonstrating cause-and-effect relations was useful because of the difficulty in demonstrating definite proof of causality between specific environmental contaminants and reproductive dysfunction in feral fish. PMID- 1908523 TI - Targeting 5'-deoxy-5'-(methylthio)adenosine phosphorylase by 5'-haloalkyl analogues of 5'-deoxy-5'-(methylthio)adenosine. AB - A series of 5'-haloalkyl-modified analogues of 5'-deoxy-5'-(methylthio)adenosine (MTA), a nucleoside byproduct of polyamine biosynthesis, has been synthesized: 5' deoxy-5'-[(2-monofluoroethyl)thio]adenosine (10), 5'-deoxy-5'-[(2 chloroethyl)thio]adenosine (4), 5'-deoxy-5'-[(2-bromoethyl)thio] adenosine (5), and 5'-deoxy-5'-[(3-monofluoropropyl)thio]adenosine (13). On the basis of their abilities to serve as substrates of MTA phosphorylase prepared from mouse liver, several of these analogues were characterized for their growth inhibitory effects in MTA phosphorylase-containing (murine L5178Y and human MOLT-4) and MTA phosphorylase-deficient (murine L1210 and human CCRF-CEM) leukemia cell lines. The MTA phosphorylase-containing tumor cell lines, especially of human origin, were found to be more sensitive to treatment by these analogues. Of the analogue series, 10 was the most potent inhibitor of growth in each of the cell lines tested. The analogues, especially compound 10, displayed a reduced capacity to alter polyamine pools relative to MTA, mechanistically indicating a decreased potential for interactions at sites other than MTA phosphorylase. The results indicate that of the analogues tested, compound 10 displayed the best inhibitor/substrate interaction with MTA phosphorylase, which, in turn, correlated with more potent growth inhibition in tumor cell lines containing MTA phosphorylase. Overall, this supports the concept that MTA phosphorylase plays a role in the activation of such analogues. PMID- 1908525 TI - The case for a cause-effect linkage between environmental contamination and development in eggs of the common snapping turtle (Chelydra S.serpentina) from Ontario, Canada. AB - Concentrations of polychlorinated biphenyls (PCBs), dibenzo-p-dioxins, and dibenzofurans, organochlorine pesticides, and their metabolites were measured in eggs of the common snapping turtle (Chelydra s.serpentina) collected from four wetlands on the shorelines of Lakes Ontario, and Erie, and one control location in central Ontario, Canada. Snapping turtle eggs from these sites were also artificially incubated to determine hatching success, and incidence of deformities in embryo and hatchling turtles. The hypothesis that elevated incidences of egg death and/or deformities of hatchling turtles would occur in populations with high concentrations of organochlorine contaminants in eggs was tested. The results were elevated using epidemiological criteria. Unhatched eggs and deformities occurred at significantly higher rates in eggs from Lake Ontario wetlands. Two of three sites from Lake Ontario had substantially higher levels of PCBs, dioxins, and furans compared to eggs from Lake Erie and the control site. It could not be shown that contamination of eggs preceded the occurrence of poor development of eggs, although excellent hatching success and low numbers of deformities in eggs from the control site were considered representative of development in healthy eggs. The statistical association between contaminant levels in eggs and poor development of these eggs supported the hypothesis that eggs from sites with the greatest contamination had the highest rates of abnormalities. PCBs were the most strongly associated chemicals, although possible effects due to the presence of other chemicals in eggs was a confounding factor. The deformities and rates of unhatched eggs were similar to those occurring in other vertebrates collected from highly contaminated areas of the Great Lakes. There were several chemicals present in the eggs that can cause similar reproductive effects in other species; therefore a specific chemical effect was not identified. Results were coherent with known statistical and biological information. Theoretical and factual evidence of PCB contamination in wild-caught snapping turtles supported and hypothesis. However, lack of controlled studies of reproductive effects of polychlorinated hydrocarbons upon this species hindered the agreement of all factual and theoretical evidence with the hypothesis. PMID- 1908526 TI - Cause-effect linkages between chemicals and populations of mink (Mustela vison) and otter (Lutra canadensis) in the Great Lakes basin. AB - Following outbreaks of reproductive failure in commercial ranching operations, laboratory experiments showed that mink are extremely sensitive to organochlorine chemicals, particularly PCBs and dioxins. The purpose of this paper is to test the hypothesis that, since wild mink are exposed to these compounds through consumption of Great Lakes fish, they might exhibit reproductive dysfunction and population declines. The otter, another piscivorous animal, should show the same effects. The available information is reviewed according to five epidemiological criteria. Harvest data are presented as a surrogate for the population status of mink and otters in certain locations around the Great Lakes. Data from Ohio show that the mink harvest between 1982 and 1987 from contaminated counties bordering Lake Erie was consistently lower (380 animals per year) than those from counties removed from Lake Erie (850 animals per year), suggesting an effect of chemicals on the status of mink populations. Preliminary studies from Ontario also suggest that mink harvest is lower in potentially "high PCB exposure areas" compared with lower exposure areas. Evidence is also presented on the harvest data for otters taken from four New York State counties adjacent to Lake Ontario and the St. Lawrence River. The harvest data from these four counties show that between 1960 and early 1970 otter harvest remained stable but has since increased. Increased harvest is consistent with improved water quality in Lake Ontario during the past 15 yr. Data relating to strength of association between chemicals and populations of mink and otter are weak and need to be further analyzed. The specificity of the effects of the chemicals on mink reproduction and mortality is well established from toxicological experiments, but there is poor resolution of the information on effects using field data. The strongest case for a causal relationship comes from consideration of the coherence criterion. In conclusion, before a causal link can be drawn between the status of mink and otter populations and exposure to organochlorine chemicals from the Great Lakes, a large amount of research and data analysis needs to be undertaken. PMID- 1908527 TI - Effects of organochlorine chemicals on the reproductive outcome of humans who consumed contaminated Great Lakes fish: an epidemiologic consideration. AB - Three sets of studies of the impacts of human exposure to PCB contaminated fish from the Great Lakes basin--the Michigan Sports Fisherman Cohort, the Michigan Maternal/Infant Cohort, and the Wisconsin Maternal/Infant Cohort-were evaluated using the epidemiologic criteria of Susser (1986). The studies were compared against each other, and against comparable data from other geographic locales. A total of seven major categories of exposure sequelae were evaluated. These ranged from the effects of primary exposure to contaminants upon maternal health status, to effects from secondary intrauterine fetal exposure, including alterations in birth size and gestational age, changes in neonatal health status, and effects persisting into early infancy. Results of the evaluations suggest that the causal hypothesis may be strongly affirmed for the relationship between PCB exposure and alterations in both neonatal health status and in health status in early infancy may be affirmed with reasonable certainty. While the evidence from the Michigan Maternal/Infant Cohort related to maternal exposure to PCB and infant size at birth and gestational age affirms the causal hypothesis, studies from other geographic locales tend only to be supportive. Analytic differences are likely responsible for this variation, but epidemiologically, the composite rating must be regarded as indeterminate. The relationship with observed alterations in maternal health status, composite activity ranking, and McCarthy Memory Scale deficits were also classified as indeterminate. No evidences of obvious negation were seen, although one portion of a study was disqualified because of incoherence. PMID- 1908528 TI - The roles of extracorporeal shock wave lithotripsy and percutaneous nephrostolithotomy in the management of pyelocaliceal diverticula. AB - Various combinations of extracorporeal shock wave lithotripsy (ESWL*) and percutaneous nephrostolithotomy were used in the treatment of 40 stone-containing caliceal diverticula in 39 patients (16 men and 23 women). Only 1 of 26 patients (4%) treated with ESWL as a single modality became stone-free, although 9 (36%) became asymptomatic. Ten patients undergoing ESWL primarily eventually required percutaneous nephrostolithotomy due to persistence of symptoms and all became stone-free. A total of 14 patients underwent a percutaneous approach as a single modality, and the diverticula in 13 of these patients became stone-free, although 2 patients did have residual parenchymal fragments. Therefore, 21 of 24 patients (87.5%) became completely free of stones using the percutaneous approach. All patients managed with percutaneous nephrostolithotomy became free of symptoms. The complex nature of access during percutaneous nephrostolithotomy favors a 1 stage approach with direct puncture into the stone-containing diverticulum. Simultaneous fulguration of the diverticulum at percutaneous nephrostolithotomy is favored, since all 17 patients in whom this technique was used had complete obliteration of the diverticulum on followup contrast studies. These data suggest that caliceal diverticula should be managed with percutaneous nephrostolithotomy, since ESWL monotherapy is unlikely to produce a stone-free or symptom-free status. PMID- 1908529 TI - A randomized comparative study of the prophylactic use of trimethoprim sulfamethoxazole versus netilmycin-metronidazole in transrectal prostatic biopsy. AB - An open randomized study was done to compare the prophylactic value of single doses of netilmycin-metronidazole versus trimethoprim-sulfamethoxazole in the prevention of postoperative infections associated with transrectal prostatic biopsy. Of 117 patients enrolled in the study 101 were evaluated and of these patients 47 received netilmycin-metronidazole and 54 received trimethoprim sulfamethoxazole. The bacteremia rate in the netilmycin-metronidazole group was 28% (13 of 47 patients) with a 95% confidence interval of 18 to 42% and in the trimethoprim-sulfamethoxazole group it was 37% (20 of 54) with a confidence interval of 26 to 50% (p = 0.43). None of the patients with bacteremia was symptomatic. Urinary tract infection rates were greater in the netilmycin metronidazole group: 17% (8 of 47 patients) versus 2% (1 of 54) in the trimethoprim-sulfamethoxazole group, p = 0.01. Trimethoprim-sulfamethoxazole (cotrimoxazole) is a better choice as an antimicrobial prophylaxis for patients undergoing transrectal prostatic biopsy. PMID- 1908530 TI - Complications following external beam radiation therapy for prostate cancer: an analysis of patients treated with and without staging pelvic lymphadenectomy. AB - We reviewed the treatment morbidity associated with definitive high energy external beam radiotherapy in 289 consecutive patients with clinically localized prostate cancer (stages A2 to C) treated from 1984 to 1988 inclusively. All patients were treated with 18 mv. photon beams via a 4-field box technique. Radiation doses ranged from 5,858 to 6,900 cGy., with a mean dose of 6,456 cGy. and a median dose of 6,400 cGy. A total of 65 patients underwent extraperitoneal pelvic staging lymphadenectomy before radiotherapy. Complications noted in 42 patients were mild (generally trivial) in 23 and moderate in 19 (6.6%). There were no severe complications. The actuarial incidence of moderate complications was 9% at 5 years. Only 6 patients experienced symptoms for longer than 6 months. The risk of complications was not increased in patients who had undergone prior lymph node dissection, and only 2 of 65 had mild lymphedema, which resolved in both cases. We conclude that high energy external beam radiation for prostate cancer can be delivered with a low risk of serious complications, even in patients who have undergone extraperitoneal staging pelvic lymphadenectomy, provided the patients are treated to limited fields with high energy photons and at doses limited to 6,800 cGy. or less. PMID- 1908531 TI - Fibrinolytic parameters in spermatozoas and seminal plasma. AB - Urokinase-type (u-PA) and tissue-type plasminogen activator antigen (t-PA) as well as plasminogen activator-inhibitor activity were determined in seminal plasma and lysates of the respective spermatozoas in 67 ejaculate of males in infertile marriage without genito urinary pathology. U-PA was determined by a competition RIA, t-PA by an ELISA and PAI by a spectrophotometric assay. 15 patients showed normozoospermia, 11 azoospermia and 41 oligoasthenoteratozoospermia (OAT-syndrome). In lysates of spermatozoas, significantly higher levels of both plasminogenactivators and PAI were found in patients with OAT syndrome as compared to those exhibiting normozoospermia. Whereas PAI was absent in the seminal plasma of normozoospermic ejaculate, patients with azoospermia (180 +/- 13 mU/ml.) and OAT-syndrome (60 +/- 5 mU/ml.) showed high PAI levels. The similarly high values of t-PA (190.8-227.8 ng./ml.) and u-PA (19.4-32 ng./ml.) in the same compartment confirm their predominantly prostatic origin and seem to have no influence on the quality of the ejaculate. PMID- 1908532 TI - [The ventilatory response to CO2 during end-expiratory negative extra-thoracic pressure and PEEP]. AB - The effects of end-expiratory negative extra-thoracic pressure (EENETP) and PEEP on the ventilatory response to CO2 were studied in seven healthy volunteers. The changes in functional residual capacity during EENETP -20 cmH2O and PEEP 5 cmH2O were 13.9 and 12.9 ml.kg-1, respectively. The slopes of CO2 response (minute ventilation/end-tidal CO2) during ZEEP, EENETP and PEEP were 0.913, 0.622, 0.693 l.min-1.mmHg-1, respectively. The slopes during EENETP and PEEP were significantly decreased. These results indicate that EENETP and PEEP could worsen the CO2 response in patients with respiratory failure, especially, with chronic obstructive pulmonary disease in which functional residual capacity is increased. PMID- 1908534 TI - Nitroglycerine tolerance. PMID- 1908533 TI - [Interferon-induced protection of renal cell cancer cell lines to lymphokine activated killer (LAK) cells and effect of acid treatment on their susceptibility. Its relevance to expression of major histocompatibility complex class I antigens on tumor cells]. AB - Renal cell cancer (RCC) cell lines, ACHN and KRC/Y, with or without exposure to interferons (IFNs), were examined for their susceptibility to lymphokine activated killer (LAK) cells in relation to modulation of major histocompatibility complex (MHC) class I antigens on tumor cells. Flow cytometric analysis demonstrated constitutional expression of class I antigen on both cell lines, which was enhanced by IFN-alpha and -gamma, and was reduced by acid treatment at pH 3. A 4-h 51Cr-release cytotoxicity assay demonstrated that pretreatment of both cell lines with IFN-alpha and -gamma decreased their susceptibility to LAK cells. Although an inverse correlation between class I antigen expression and susceptibility to LAK cells has been reported by others, IFN and acid treatment demonstrated that the degree of class I antigen expression did not correlate with the susceptibility to LAK cells. These results suggest that clinically administered IFNs might induce protection of RCC to LAK cells, and that decrease of susceptibility might depend upon a mechanism different from the enhancement of class I antigens which is frequently expressed on RCC. PMID- 1908535 TI - [25 years progress in tubercule bacillus research--report of tuberculosis panels in silver jubilee of the Japan-U.S. Cooperative Medical Science Program]. PMID- 1908536 TI - [A study on drug resistance of newly admitted pulmonary tuberculosis patients. Part 1. Prevalence of drug resistance according to the sensitivity test at local laboratories, and its trend over 25 years in Japan. Tuberculosis Research Committee, (Ryoken)]. AB - As a part of the epidemiological surveillance for the resistance to anti tuberculosis drugs in pulmonary tuberculosis patients, successive surveys of the prevalence of resistance to tuberculosis drugs were conducted by Tuberculosis Research Committee "Ryoken". The prevalence of drug resistance according to the sensitivity test at local laboratories was reported as follows from the results of the ninth survey conducted in 1982. 1. In 1957, the percentage of the patients without history of previous chemotherapy among the newly admitted patients to hospital was only 17.8%, but it increased in each survey reaching 64.2% in 1982. 2. According to the results of sensitivity tests at local institutions, the prevalence of initial resistance to at least one of SM, INH and/or PAS was 13.6%, and that to each of the drug was 8.8%, 4.2% and 5.1%, respectively. 3. Prevalence of acquired resistance to at least one of SM, INH and/or PAS among newly admitted patients with history of previous treatment was 54.0% in 1957, and it increased in each survey reaching 65.4% in 1963. Since then, it decreased gradually, and became 40.1% in 1982. Decrease in the prevalence of acquired resistance was statistically confirmed. PMID- 1908537 TI - [Study of detailed conditions in DNA probe test by use of Gen-Probe Rapid Diagnostic System for identification of Mycobacterium avium complex and Mycobacterium tuberculosis complex]. AB - In order to improve feasibility of technical procedures in Gen Probe Rapid Diagnostic System (Gen Probe Inc., San Diego, CA, U.S.A.) for identification of Mycobacterium avium complex (MAC) and M. tuberculosis complex (MTC), we studied several test conditions in the DNA probe testing, such as stability of test bacterial suspension, optimal duration of bacterial cultivation, the number of organisms in test bacterial suspension required for accurate determination, and so on. With respect to concentration of organisms (MAC and MTC) in test bacterial suspension (0.1ml), we found that 5-fold dilution as well as 5-fold condensation of the standard bacterial suspension (McFarland No.1) gave substantially the same result as in the case where bacterial suspension at the standard concentration was used. This indicates that the test bacterial suspensions (0.1ml) containing either 1.5 X 10(7)-5 X 10(8) of MAC or 3 X 10(5)-8 X 10(6) of MTC are available for the DNA probe testing. Test bacterial suspension at McFarland No.1 prepared from fresh cultures (3-4 week-old) could be stored either at -80, -20 or 4 degrees C at least for 17 weeks without significant loss of reactivity to M. avium, M. intracellulare and MTC DNA probes. In this case, stability of DNA probe reactivity was preserved in the following order: MTC, M. avium and M. intracellulare. Concerning the age of bacterial cultures, at least 16-week-old cultures of MAC and MTC after initial appearance of cell growth on 1% Ogawa's egg media were sufficiently reactive to either MAC or MTC DNA probe. In this case, MTC showed most stable reactivity during the course of long-term cultivation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1908539 TI - [Study of the effectiveness of nitroglycerin infusion in patients with unstable stenocardia]. PMID- 1908538 TI - [Signs of thrombin formation in venous occlusion in patients with ischemic heart disease and the role of the protein C activation system in its utilization]. AB - Elevated levels of fibrin peptide A were found in venous occlusion only in the patients unconsuming C protein, which indicates that there is a relationship between the thrombin production processes during venous occlusion and the C protein system functioning, the anticoagulant function of the endothelium in particular. Moreover, this makes it possible to employ the standard venous occlusion test to make an integral assessment of endothelial function. PMID- 1908541 TI - [Hormonal changes in transient cerebral ischemia in young women]. AB - Examination of 20 females aged 24-45 showing transient disturbances of cerebral circulation included measurement of serum concentrations of FSH, LH and estradiol at varying phases of the menstrual cycle. It was found out that estradiol and LH levels fell during the ovulation peak of the menstrual cycle. Transient defective circulation in the brain of young women is thought to result from anovulation, predominantly low-estrogen menstrual cycle. Attenuation of sexual function seems to promote transient disturbances of cerebral circulation. PMID- 1908540 TI - [Nutrition disorders in patients with acute calculous cholecystitis]. AB - The study of 226 patients with acute calculous cholecystitis provided arguments in favour of I. V. Davydovsky ideas on pyoresorptive fever: there was suppuration, resorption, protein loss. Anthropometric parameters remained stable in the presence of hypoalbuminemia, hypovolemia. Hypoproteinemia is attributed to stress evident from high cortisol level in the plasma from hospitalized patients. These shifts in nutritional status are unfavorable for forthcoming surgery. Transcutaneous transhepatic puncture and laparoscopy of the gall bladder are able to correct unwanted effects and prepare the patients for radical surgery. PMID- 1908542 TI - [IgM myeloma: a report of 2 cases]. AB - The IgM myeloma is a rare type of multiple myeloma (MM) with some features which differentiate it from other immunologic types of myeloma and from Waldenstrom macroglobulinemia (WM). Two patients with IgM myeloma in whom the only clinical feature of the disease was the development of bone lesions and general deterioration are reported. In none of the cases an M component was detected in proteinogram. A bone marrow proliferation of plasma cells was discovered in both, which it was accompanied with dura mater infiltration in one of them. The type of secreted immunoglobulin was IgM lambda in the first case and kappa in the second. Both patients had a poor clinical course after the diagnosis and died due to infective complications. Emphasis is made on the need to differentiate this condition from WM due to their different prognosis and therapy. PMID- 1908543 TI - Effects of topical dihydroergocristine on intraocular pressure, aqueous humor dynamics and pupil diameter in conscious rabbits. A comparative study with timolol and pilocarpine. AB - This work comparatively studies the effects of dihydroergocristine, timolol and pilocarpine on intraocular pressure and pupil diameter in conscious rabbits. Intraocular pressure was measured by applanation tonometry and the pupil diameter by a photographic technique. In anesthetized rabbits, changes in tonographic facility of aqueous humor outflow and rate of aqueous humor formation were evaluated. Dihydroergocristine reduced the intraocular pressure more than timolol and much more than pilocarpine. The ocular hypotensive effect of dihydroergocristine was accomplished by a great reduction in aqueous humor formation, which surpasses the decrease in aqueous humor outflow, while timolol mainly reduced aqueous humor formation and pilocarpine increased aqueous humor outflow. Pupil diameter remained unchanged on dihydroergocristine, whereas timolol induced a slight mydriasis and pilocarpine provoked a clear myosis. Effects of dihydroergocristine might result in blockade of alpha-adrenoceptors in ciliary body, although available data about pretreatment with either metoclopramide or domperidone suggest that dopamine DA2-receptors might participate in ocular hypotensive effect of ergot derivatives. PMID- 1908544 TI - A drug for prevention of anthracycline-induced cardiac toxicity. PMID- 1908545 TI - [Non-invasive intermittent self-ventilation as therapy of chronic respiratory failure]. AB - Noninvasive intermittent ventilation (NIV) is performed as controlled mechanical ventilation to put the inspiratory muscles at rest and to normalize the arterial blood gases. As access to the airways an individual nasal mask was used. weaning from tracheostoma ventilation had failed after 74 days on average. 27 patients were treated, when hypercapnic ventilatory failure had not improved within three weeks of conventional therapy (eight patients with kyphoscoliosis, 15 COPD, six neuromuscular disease, three sequelas of tbc). During NIV, there was an increase in inspiratory muscle force, indicated by an increase in maximal inspiratory mouth occlusion from 42 to 58 cm H2O (p less than 0.01). With this increase in muscular force, spontaneous minute volume increased, resulting in an increase in pO2 from 56 to 70 mm Hg (p less than 0.001) and a decrease in pCO2 from 53 to 43 mm Hg (p less than 0.001), as well as an increase in exercise capacity. NIV therefore can improve hypercapnic ventilatory failure effectively. It can be used early in chronic respiratory failure, during weaning from mechanical ventilation, allowing the early and costsaving discharge from the ICU. PMID- 1908546 TI - [Changes in fecal composition, intestinal transit, bile acid metabolism and intestinal fermentation in long-term nutrition with high molecular weight formula diet]. AB - Treatment with formula diets becomes more and more popular in many patients. The influence of those diets on gut functions is as yet poorly known. We studied in ten healthy volunteers the effects of a high molecular liquid diet. Despite of a sufficient energy supply the volunteers lost significantly weight which may be related to an acceleration of small bowel transit (60 +/- 9 min vs. 31 +/- 5 min; control vs. diet period). Whole gut transit did not change significantly (52 +/- 3 h vs. 56 +/- 3 h). The fecal excretion of bile acids decreased significantly (293 +/- 35 mg/24 h vs. 151 +/- 10 mg/24 h) which was particularly due to a decrease of primary bile acids. The serum bile acid concentrations behaved in a similar way (total bile acids: 3.19 +/- 0.66 mumol/l vs. 1.71 +/- 0.21 mumol/l). Neither the determination of unconjugated serum bile acids nor hydrogen breath testing did indicate increase of bacterial growth. In conclusion, chronic nutrition with formula diets causes significant changes of gut functions. PMID- 1908547 TI - A 10-year report of patients in a prolonged respiratory care unit. AB - The author statistically analyzes 542 patients who were hospitalized in the Prolonged Respiratory Care Unit of Bethesda Lutheran Medical Center in St. Paul, Minnesota, between 1979 and 1989. A demographic description of the patients, an analysis of discharge status, and a discussion of reimbursement for care are presented. It is apparent from this analysis that: 1) there is a large number of patients who will require chronic ventilator support, 2) weaning of "unweanable" patients can occur in selected cases and can be most expeditiously accomplished in specialized units, 3) these specialized units are cost effective, and early transfer from the DRG-reimbursed ICUs would benefit not only the patient but also the reimbursing agent and referral hospital, 4) specialized, adequately funded centers for unweanable patients need to be developed, and 5) further studies and education concerning the imprudent use of ventilators must be implemented by the appropriate physician organizations. PMID- 1908548 TI - Inhibitory GTP-binding regulatory protein Gi3 can couple angiotensin II receptors to inhibition of adenylyl cyclase in hepatocytes. AB - Angiotensin II can inhibit hormone-stimulated adenylyl cyclase in intact hepatocytes or in hepatic membrane preparations. Because the response can be blocked by pertussis toxin, the object of the present study was to determine which of the known variants of Gi can couple angiotensin II receptors to inhibition of adenylyl cyclase. The potential candidates were identified by probing RNA isolated from rat hepatocytes with cDNAs specific for the alpha subunits of known toxin-sensitive guanine nucleotide-binding regulatory proteins (G proteins). Hepatocytes contained no detectable RNA for the Go or Gi1 alpha subunits and similar levels of RNA coding for the Gi2 and Gi3 alpha subunits. To determine whether Gi3 could couple angiotensin receptors to inhibition of cyclase, membranes were prepared from hepatocytes whose G proteins were fully ADP ribosylated with pertussis toxin, and the Gi3 holoprotein purified from rabbit liver was reconstituted into the membranes. The nature of the Gi3 reconstituted into the membrane was assessed by immunoblotting with antibodies specific for the Gi alpha subunits. Reconstitution of 6-10 pmol of Gi3/mg of membrane protein into the toxin-treated membranes restored the ability of 10 nM angiotensin II to inhibit adenylyl cyclase. Because pertussis toxin has nonspecific effects, an assay was developed to measure the interaction of the angiotensin receptor with reconstituted G proteins in normal membranes. In the presence of Mg2+, guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) caused a reduction of the affinity of the angiotensin II receptor for 125I-angiotensin II that was stable to washing and the detergents used to reconstitute G proteins into the membranes. Using this protocol to activate G proteins and "uncouple" receptors, the ability of the GDP liganded form of Gi to restore high affinity binding was examined. Reconstitution of about 10-15 pmol of oligomeric Gi3/mg of membrane protein restored both the high affinity state of the angiotensin II receptor and the ability of GTP gamma S to shift the affinity to a lower state. The same shift in receptor affinity could be accomplished by reconstituting the Gi3 alpha subunit, resolved free of beta gamma subunits, into the membranes. Reconstitution of up to 50 pmol of Gs/mg of membrane protein had no effect on angiotensin II receptor affinity. The results suggest that a major form of Gi in hepatocytes is Gi3 and that it can couple angiotensin receptors to inhibition of adenylyl cyclase. PMID- 1908549 TI - Selective inhibition of glucuronidation by 2,2,2-triphenylethyl-UDP in isolated rat hepatocytes: conjugation of harmol, 3,3',5-triiodothyronine, and N-hydroxy-2 acetylaminofluorene. AB - 2,2,2-Triphenylethyl-UDP (TPEU) was synthesized as an analogue of the transition state of the glucuronidation reaction catalyzed by UDP-glucuronosyltransferase; it contains both a uridine and an acceptor substrate moiety. It inhibits rat liver microsomal UDP-glucuronosyltransferase [Eur. J. Biochem. 188:309-312 (1990)]. In the present work, TPEU was tested as an inhibitor of glucuronidation in intact rat hepatocytes. Two phenols (harmol and 3,3',5-triiodothyronine) and a hydroxamic acid (N-hydroxy-2-acetylaminofluorene) were used as substrates for glucuronidation. The glucuronidation of these substrates was strongly decreased by TPEU at 0.3-5 mM. Up to 5 mM TPEU did not kill the cells, as shown by unimpaired trypan blue exclusion at the end of the incubation. When glucuronidation was inhibited, the sulfation of harmol increased, as did the production of reactive species generated from N-hydroxy-2-acetylaminofluorene that bind to cellular macromolecules. This indicates that a decreased substrate consumption by loss of glucuronidation leads to increased conversion by competing pathways. The results show, therefore, that TPEU is an effective inhibitor of glucuronidation in this cellular system in vitro. PMID- 1908550 TI - Analysis of age-associated alteration in the synthesis of HMG nonhistone proteins of the rat liver. AB - HMG proteins were extracted with 5% PCA or 0.35 M NaCl from whole tissue, nuclei or chromatin of the liver of young (19 weeks) and old (118 weeks) male rats. They were resolved on acetic acid-urea polyacrylamide gel. The electrophoretic patterns of the major HMG proteins 1, 2, 14 and 17 of both ages are similar. The in vitro synthesis of HMG 1 and 2 decreases, but that of HMG 14 and 17 increases considerably in the liver of old rats. The synthesis of different HMG proteins is modulated differentially by spermine, butyrate, dexamethasone and 3 aminobenzamide in the liver of young and old rats. These findings suggest that HMG proteins contribute to alterations in the organization of chromatin and expression of genes during aging. PMID- 1908551 TI - Leukemia inhibitory factor and interleukin-6 trigger the same immediate early response, including tyrosine phosphorylation, upon induction of myeloid leukemia differentiation. AB - Leukemia inhibitory factor (LIF) and interleukin-6 (IL-6), two multifunctional cytokines lacking structural homology and binding to distinct receptors, share interesting functional similarities, which include induction of hematopoietic differentiation in normal and myeloid leukemia cells, induction of neuronal cell differentiation, and stimulation of acute-phase protein synthesis in hepatocytes. Structural information on the LIF receptor is not yet available, whereas recent cloning of the IL-6 receptor has shown it to be bipartite, with a signal transducing subunit that lacks sequence homology to known protein kinases and produces second messengers of unknown nature. The molecular nature of the mechanisms which LIF and IL-6 use to induce cell differentiation is not known. To address this issue, we took advantage of a clone of M1 myeloblastic leukemia cells capable of being induced for terminal differentiation by both LIF and IL-6 directly activate the same set of immediate early response genes upon induction of M1 myeloid differentiation. At least two mechanisms of gene activation, one transcriptional and the other posttranscriptional, are shown to be involved. It is also shown that the LIF and IL-6 immediate early response, at suboptimal cytokine concentrations, is additive. Using a variety of protein kinase activators and inhibitors, we have shown that the intracellular signalling pathways for both LIF and IL-6 are distinct from those of known second messengers and involve protein phosphorylation, notably tyrosine phosphorylation of a 160 kDa protein, as an essential step(s) in the immediate early activation of MyD gene expression. These observations indicate that the functional similarities of LIF and IL-6 as inducers of cell differentiation prevail at the level of the complex differentiation immediate early response and implicate common mechanisms of signal transduction for LIF- and IL-6-induced differentiation. PMID- 1908552 TI - Specific binding of chloroplast proteins in vitro to the 3' untranslated region of spinach chloroplast petD mRNA. AB - A detailed analysis of RNA-protein complex formation in the 3' untranslated region of spinach chloroplast petD mRNA has been carried out. Five chloroplast proteins that interact with petD RNA in this region, which contains an inverted repeat sequence capable of forming a hairpin structure, have been identified. A 33-kDa protein recognizes specifically the double-stranded stem of the hairpin structure; mutations that disrupt base pairing at the base of the stem reduce or eliminate protein binding. A 57-kDa protein recognizes specifically an AU-rich sequence motif that is highly conserved in petD genes of different higher plant species. The 57-kDa protein and possibly the 33-kDa protein form stable complexes with petD RNA in vitro and may interact with each other. In addition, their interaction with petD RNA is highly sensitive to heparin. The three other proteins, of 100, 32, and 28 kDa, display little sequence or structural binding specificity apart from their preference for uridine-rich sequences. They also interact with the 3' untranslated regions of other chloroplast RNAs such as those of psbA and rbcL. The functions of these proteins in the regulation of petD gene expression, including possible roles in transcription termination and RNA stability, are discussed. PMID- 1908553 TI - The jun and fos protein families are both required for cell cycle progression in fibroblasts. AB - The expression of different members of the Jun and Fos families of transcription factors is rapidly induced following serum stimulation of quiescent fibroblasts. To determine whether these proteins are required for cell cycle progression, we microinjected affinity-purified antibodies directed against c-Fos, FosB, Fra-1, c Jun, JunB, and JunD, and antibodies that recognize either the Fos or the Jun family of proteins, into Swiss 3T3 cells and determined their effects in cell cycle progression by monitoring DNA synthesis. We found that microinjection of anti-Fos and anti-Jun family antibodies efficiently blocked the entrance to the S phase of serum-stimulated or asynchronously growing cells. However, the antibodies against single members of the Fos family only partially inhibited DNA synthesis. In contrast, all three Jun antibodies prevented DNA synthesis more effectively than did any of the anti-Fos antibodies. PMID- 1908556 TI - An open pilot study of bupropion and psychotherapy for the treatment of cocaine abuse in methadone-maintained patients. PMID- 1908554 TI - Assessment of the transcriptional activation potential of the HMG chromosomal proteins. AB - Chromosomal proteins HMG-14, HMG-17, and HMG-1 are among the most abundant, ubiquitous, and evolutionarily conserved nonhistone proteins. Analysis of their structure reveals features which are similar to those of certain transcription factors. The distribution of charged amino acid residues along the polypeptide chains is asymmetric: positive charges are clustered toward the N-terminal region, while negative charges are clustered toward the C-terminal region. The residues in the C-terminal region have the potential to form alpha helices with negatively charged surfaces. The abilities of HMG-14, -17, and -1 to function as transcriptional activators were studied in Saccharomyces cerevisiae cells expressing LexA-HMG fusion proteins (human HMG-14 and -17 and rat HMG-1) which bind to reporter molecules containing the beta-galactosidase gene downstream from a lexA operator. Fusion constructs expressing deletion mutants of HMG-14, -17, and -1 were also tested. Analysis of binding to the lexA operator with in vitro synthesized fusion proteins shows that there are more sites for HMG-14, -17, and 1 binding than for LexA binding and that only the fusion constructs which contain the C-terminal, acidic domains of HMG-17 bind the lexA operator specifically. None of the LexA-HMG fusion protein constructs elevate the level of beta galactosidase activity in transfected yeast cells. Thus, although HMG-14, -17, and -1 are structurally similar to acidic transcriptional activators, these chromosomal proteins do not function as activators in this test system. PMID- 1908557 TI - Aminoalkylindoles (AAIs): a new route to the cannabinoid receptor? PMID- 1908555 TI - A codon change in beta-tubulin which drastically affects microtubule structure in Drosophila melanogaster fails to produce a significant phenotype in Saccharomyces cerevisiae. AB - The relative uniformity of microtubule ultrastructure in almost all eukaryotic cells is thought to be a consequence of the conserved elements of tubulin sequence. In support of this idea, a mutation in a beta-tubulin gene of Drosophila melanogaster, occurring at a highly conserved position, produces U shaped microtubules, suggesting a defect in either nucleation or packing during assembly (M. T. Fuller, J. H. Caulton, J. A. Hutchens, T. C. Kaufman, and E. C. Raff, J. Cell Biol. 104:385-394, 1987, and J. E. Rudolph, M. Kimble, H. D. Hoyle, M. A. Subler, and E. C. Raff, Mol. Cell. Biol. 7:2231-2242, 1987). Surprisingly, we find that introducing the same mutation into the sole beta-tubulin gene of Saccharomyces cerevisiae has virtually no consequences for microtubule structure or function in that organism. PMID- 1908558 TI - Sustained release injectable naltrexone microcapsules. PMID- 1908559 TI - Sensitization to cocaine produced by injection of pertussis toxin into the A10 dopamine region. PMID- 1908560 TI - Immune effects of opiates in test tubes and monkeys. PMID- 1908561 TI - Response to Ptashne. PMID- 1908562 TI - Regulation of fast inactivation of cloned mammalian IK(A) channels by cysteine oxidation. AB - Modulation of neuronal excitability by regulation of K+ channels potentially plays a part in short-term memory but has not yet been studied at the molecular level. Regulation of K+ channels by protein phosphorylation and oxygen has been described for various tissues and cell types; regulation of fast-inactivating K+ channels mediating IK(A) currents has not yet been described. Functional expression of cloned mammalian K+ channels has provided a tool for studying their regulation at the molecular level. We report here that fast-inactivating K+ currents mediated by cloned K+ channel subunits derived from mammalian brain expressed in Xenopus oocytes are regulated by the reducing agent glutathione. This type of regulation may have a role in vivo to link metabolism to excitability and to regulate excitability in specific membrane areas of mammalian neurons. PMID- 1908563 TI - Co-engagement of CD8 with the T cell receptor is required for negative selection. AB - Although it is established that the CD8 and CD4 co-receptors are involved in T lymphocyte recognition and activation in the periphery, it is less clear whether these molecules participate in thymic selection events. Analysis of thymic selection in mice transgenic for T cell-receptor genes or for major histocompatibility complex (MHC) genes, or mice injected with antibodies against CD8, CD4 or MHC molecules, is consistent with the participation of CD8 and CD4 in thymic selection. But antibody-mediated crosslinking of surface receptors in thymic organ cultures has indicated that CD8 is not involved in thymic deletion. We show here that mice transgenic for a mutant MHC class I molecule that cannot interact with CD8 do not delete CD8-dependent T cells reactive with the wild-type molecule. This finding unequivocally establishes that for negative selection in the thymus, CD8 must interact with the same MHC class I molecule as the T cell receptor. PMID- 1908564 TI - Cell-surface receptor for ecotropic murine retroviruses is a basic amino-acid transporter. AB - The complementary DNA sequence encoding the cell-surface receptor for ecotropic host-range murine retroviruses (ecoR) shows that it contains 622 amino acids and 14 hydrophobic potentially membrane-spanning sequences. Because this receptor occurs on many or all murine cells and is probably essential for viability of cultured fibroblasts, its normal function might be to transport an essential metabolite. We expressed ecoR in Xenopus laevis oocytes by injecting RNA transcribed from the cloned cDNA. These oocytes specifically bound the gp70 envelope glycoprotein from an ecotropic murine leukaemia virus. An inward current was recorded electrophysiologically when a mixture of amino-acids was applied: this resulted from a stereoselective, saturable uptake of lysine, arginine and ornithine; it was independent of sodium and not substantially altered by gp70. Cysteine and homoserine were also taken up, but sodium was necessary for their transport. These properties of ecoR correspond to those of the y+ amino-acid transporter. Our results demonstrate the subversion of a ubiquitous cell membrane protein, in this case a basic amino acid transporter, for use as a retroviral receptor. PMID- 1908565 TI - Influence of aging on the acute depletion of reduced glutathione induced by electrophilic agents. AB - A severe age-dependent depletion of reduced glutathione (GSH) occurs in rat forebrain at 1-3 h from intraperitoneal injection of the electrophilic agents cyclohexene-1-one and cycloheptene-1-one. Chronic pretreatment with central dopamine agonists (i.e., ergot alkaloids; particularly, dihydroergocriptine) partially counteracts the GSH depletion induced in 15-month-old forebrains by the prooxidants tested. In contrast, chronic pretreatment with a vasodilator agent (i.e., papaverine) magnifies the GSH depletion. PMID- 1908566 TI - Privatisation--is it a viable option? PMID- 1908567 TI - Annual meeting of the American Academy of Otolaryngology--Head and Neck Surgery Foundation, Inc. Kansas City, Missouri, September 22-26, 1991. Instruction course program. PMID- 1908568 TI - Annual meeting of the American Academy of Otolaryngology--Head and Neck Surgery Foundation, Inc. Kansas City, Missouri, September 22-26, 1991. Abstracts. PMID- 1908569 TI - Closed-wound drainage systems. The Solcotrans Plus versus the Stryker-CBC ConstaVAC. AB - Ninety-six patients (63 females and 33 males) who underwent total joint arthroplasty or spinal reconstructive surgery were randomized to receive either a Solcotrans Plus or a Stryker-CBC ConstaVAC closed-wound drainage system. A binomial test showed that the Stryker-CBC ConstaVAC system was significantly preferred over the Solcotrans Plus system for ease of use, as reported by nurses. However, Solcotrans Plus was more cost-effective because a larger volume of blood shed by a patient could be reinfused while maintaining the standards of the American Association of Blood Banks. The difference in the occurrence of side effects between the two systems was not statistically significant. PMID- 1908570 TI - Disseminated infection with Pseudallescheria boydii in a patient with chronic granulomatous disease: response to gamma-interferon plus antifungal chemotherapy. PMID- 1908571 TI - Mixed mycobacterial infection of cervical lymph nodes. PMID- 1908573 TI - Selection of medical devices. PMID- 1908572 TI - Calcitonin-gene-related peptide activates the muscarinic-gated K+ current in atrial cells. AB - A high density of nerve fibers containing calcitonin-gene-related peptide (CGRP) is present in the atria. Recently CGRP was reported to open ATP-sensitive K channels in arterial smooth muscle cells. This study examines whether CGRP activates a similar K+ channel in cardiac cells. In voltage-clamped whole cells loaded with GTP and ATP, CGRP reversibly evoked an inwardly rectifying K+ current. To identify the K+ channel that gives rise to this current, three types of K+ channel (resting, ATP-sensitive and acetylcholine-activated) were examined. CGRP failed to activate or inhibit the ATP-sensitive or the resting K+ channel. However, CGRP (0.1-1 microM) caused activation of single channels with kinetics similar to that of the muscarinic K+ channel (35-40 pS conductance and approx. 1 ms mean open time in symmetrical 140 mM K+). In excised, inside-out (CGRP in pipette) or in outside-out (GTP in pipette) patches, the K+ current was activated by perfusion with GTP or CGRP, respectively, suggesting that CGRP activated the muscarinic K+ channel via GTP-binding protein. Treatment with pertussis toxin inhibited the activation of the K+ channel, suggesting that CGRP receptor may be coupled to a Gi or a Go type of GTP-binding protein. Together with previous findings, these results suggest that CGRP modulates several types of ion channels to produce its cellular effects. PMID- 1908574 TI - Trauma to elbows, knees, and ankles. AB - In summary, the emergency department or office-based physician should distinguish first between inflammation and injury. A clinical diagnosis of fracture should be made before obtaining and reading films. Comparison views help to resolve doubt. A neurologic examination should be documented before undertaking reduction. Finally, if in doubt, a splint for 24 to 48 hours until an orthopedic opinion is available causes no harm. PMID- 1908575 TI - Congenital histiocytosis. A heterogeneous group of diseases, one presenting as so called congenital self-healing histiocytosis. AB - Three cases of congenital histiocytic disorders--generalized Langerhans cell histiocytosis, generalized juvenile xanthogranuloma and so-called congenital self healing histiocytosis are compared using histiochemical, immunohistochemical and ultrastructural methods. The results showed a typical morphological pattern of Langerhans cell histiocytosis (S 100+, CD 1+, alpha-mannosidase +) with an unusual self-healing cutaneous phenomenon. The congenital self-healing histiocytosis showed a non-Langerhans cell immunophenotype (CD 14+, CD 1-, S 100 ) and morphological appearance resembling the evolutive "early" stage of juvenile xanthogranuloma. A diffuse cellular positivity of alpha-mannosidase in juvenile xanthogranuloma and congenital self-healing histiocytosis differed from a typical perinuclear globular positivity of this enzyme in Langerhans cell histiocytosis. It is concluded that congenital self-healing histiocytosis may in some cases be of non-Langerhans cell type and under this term a clinically characteristic syndrome of histiocytic proliferation of Langerhans cells or tissue histiocytes may be included. PMID- 1908576 TI - Distribution of endogenous viruses in some commercial chicken layer populations. AB - The distribution of endogenous virus (ev) genes was studied in five commercial layer lines; four were brown-egg types and one was White Leghorn. The DNA samples were obtained from nine birds of each line and digested with SacI and BamHI endonucleases. The DNA fragments were separated by gel electrophoresis, and Southern blots were prepared and examined for the presence of ev genes following hybridization with the labeled recombinant plasmid pRAV-2 and autoradiography. Almost all fragments were present in more than one line, suggesting that each line has drawn a random assortment of ev genes from the same common pool, possibly as a founder effect. A great degree of polymorphism is shown by the ev genes in the lines investigated. Most fragments were present at low or intermediate frequencies. Very few fragments were present in only one line or in only one bird. This suggests that de novo integration of ev genes at new sites is a relatively rare event. Very few fragments were present at high frequencies, and none of the fragments, except for the BamHI internal fragments, were present in all birds of all lines. Considering that ev genes are present in the wild progenitor of the domestic chicken, the lack of fixation of any ev genes in the chicken genome is remarkable. It is proposed that ev genes have general deleterious effects in the chicken (hence, the lack of fixation), but those ev genes that have been retained in the chicken genome have favorable effects under some circumstances with consequent equilibrium at low to intermediate frequencies. It is speculated that the retained ev genes may represent sites of favorable mutation via insertional mutagenesis and, hence, a potential route to the cloning of genes of economic importance in poultry. PMID- 1908577 TI - The relationship between dietary crude protein and dietary lysine requirement by broiler chicks on diets with and without the "ideal" amino acid balance. AB - Experiments were designed with groups of broiler chickens to test whether the requirement for dietary lysine was related to the CP content of diets that had either a surplus or the recommended requirement of critical amino acids. Diets of equal energy were formulated using a summit and basal diet to obtain a range of CP contents from 14 to 26% (Experiment 1) with surplus critical amino acids or from 12 to 25% (Experiment 2) with the "ideal" amino acid balance. In both experiments at each CP level, there was an optimum lysine content for weight gain and feed conversion ratio (FCR). Diets with ideal amino acid balances gave less of a response as measured by growth rate and FCR than those with surpluses. Combining all data gave a significant improvement in both weight gain and FCR with increasing intake of dietary lysine. It would appear that because performance was highest on diets with the highest crude protein, there may be a requirement for CP per se. Alternatively, because all diets contained substantial amounts of synthetic amino acids, broilers may have a requirement for amino acid peptides that is not met by free amino acids. PMID- 1908578 TI - Influence of virginiamycin on growth and efficiency of large white turkeys. AB - Efficacy of virginiamycin (22 mg/kg) in combination with no drug, amprolium, carbarsone, halofuginone, or monensin, was studied. Male and female turkeys were raised to market age in five experiments conducted from 1983 to 1987. Body weights and feed:gain responses to virginiamycin for males and females were positive and significant (P less than .05). Virginiamycin resulted in mean 5.2 and 6.3% body weight responses and 3.3 and 2.2% feed:gain responses for males at 19 or 20 wk of age and for females at 16 or 17 wk of age, respectively. Mortality rates were low in all studies, and were not influenced by virginiamycin. In a processing study, virginiamycin in combination with halofuginone did not affect shrinkage, yield, or market grade. Feed was utilized by males and females 3.9 and 3.0%, respectively, more efficiently than expected with dietary virginiamycin, compared with results predicted by a simulation modeling technique. Profitability was considerably greater with dietary virginiamycin using actual data than with simulated feed consumption data. PMID- 1908579 TI - Dietary modification of yolk lipid with menhaden oil. AB - Due to the numerous proposed cardiovascular benefits associated with consumption of omega-3 fatty acids, marketing of an egg enriched by omega-3 fatty acid may benefit the egg producer. Effects on yolk composition of a standard laying hen diet enriched with 3% menhaden oil (test diet), versus an isocaloric (control) diet containing no added fat, were evaluated for 18 wk. Dietary menhaden oil did not alter egg production, egg weight, total yolk fat, or yolk cholesterol. However, yolk contents of omega-6 and omega-3 fatty acids were influenced by diet. Arachidonic acid decreased and eicosapentaenoic acid increased in eggs from hens fed the test diet following 1 wk of dietary treatment. Docosahexaenoic acid and linolenate increased in eggs from hens fed the test diet at 2 and 3 wk of the trial, respectively. These alterations in yolk composition resulted in a decrease in the ratio of omega-6 to omega-3 fatty acids from 18 for eggs from hens fed the control diet to 3 for eggs from hens fed the test diet. At Weeks 14 and 18, hens (n = 10 per diet) were killed and necropsied. No change in gross scoring of hepatic lipidosis was observed. Histologically, significantly greater scores for hepatocellular lipid infiltration were recorded for liver sections from hens fed menhaden oil than for control hens. Increased microscopic hepatic lipid infiltration observed with dietary omega-3 administration may have significance for flocks predisposed to fatty liver syndrome and may also provide a unique system in which to study the effects of dietary omega-3 fatty acids on liver lipid metabolism. PMID- 1908580 TI - Novel arachidonate metabolites generated by cytochrome P450-dependent mono oxygenases. AB - Cytochrome P450-dependent arachidonic acid (AA) metabolism by medullary thick ascending limb of the loop of Henle (mTALH) cells, corneal epithelium and other transporting epithelia, such as those of the intestines, generate metabolites which affect Na(+)-K(+)-ATPase activity, vasomotion and, thereby, organ function. Further, these novel AA metabolites contribute to the control of blood pressure in the SHR through participation in the local control of blood flow and in the regulation of extracellular fluid volume. PMID- 1908581 TI - Picroliv protects against monocrotaline-induced hepatic damage in rats. AB - Monocrotaline, a pyrrolizidine alkaloid, caused changes in most of the biochemical parameters in rats 12 days after a single dose of 120 mg/kg. These included significantly increased activities of hepatic succinate dehydrogenase, acid ribonuclease, acid phosphatase, gammaglutamyl transpeptidase and 5' nucleotidase and decreased in the activities of glucose-6-phosphatase and cytochrome P450. The levels of DNA, RNA and glycogen in liver and albumin and protein in serum decreased while serum bilirubin increased. The histopathological changes in liver were characterized by diffused hepatocyte alterations in the form of ballooning, granular cytoplasm, indistinct cell outlines, nuclear changes, focal necrosis, and vascular damage. When picroliv, a standardized iridoid glycoside fraction of Picrorhiza kurroa, was administered orally in a dose of 25 mg/kg simultaneously with monocrotaline, alterations in most of the biochemical parameters along with the histopathological changes in liver caused by monocrotaline were prevented. PMID- 1908582 TI - Chronic nicotine treatment enhances the depressor responses to arachidonic acid in the rat. AB - The depressor responses to intravenous injections of arachidonic acid, prostacyclin (PGI2), prostaglandin E2 (PGE2) and sodium nitroprusside were studied in chronically nicotine-treated rats. Arachidonic acid, PGI2, PGE2 and sodium nitroprusside decreased the diastolic blood pressure dose-dependently in the control animals. The vasodepressor effect of arachidonic acid was significantly enhanced in rats given nicotine 5 and 25 micrograms/ml in their drinking water for 10 days but remained unchanged in the animals treated with 1 microgram/ml nicotine for 10 days or given 1 mg/kg i.v. nicotine 10 min before administration of arachidonic acid. Indometacin abolished arachidonic-acid induced depressor responses in both the control and nicotine-treated rats. Hypotension induced by PGI2, PGE2 and sodium nitroprusside was of similar magnitude in the control and nicotine-treated animals. It is suggested that the enhancement by chronic nicotine treatment of depressor responses to arachidonic acid could be due to changes in the formation and/or removal of its vaso-active metabolites (i.e. prostacyclin and/or thromboxane A2). PMID- 1908583 TI - Protective effects of misoprostol on carbon tetrachloride-induced liver damage in the rat. AB - Effects of misoprostol on histologic and biochemical alterations caused by CCl4 were investigated in the rat. Misoprostol protected against CCl4-induced liver injury. A close correlation occurred between biochemical data and morphological changes. This hepatoprotective effect was observed only when misoprostol was given 30 min before CCl4. PMID- 1908585 TI - Piecing together the crazy quilt of prenatal care. AB - The failure to provide adequate prenatal care for low-income pregnant women in the United States and the effects of this failure on infant mortality are well known. Many studies have identified institutional barriers against access to care as a major cause. To overcome these barriers, Public Health District V, South Central Idaho, has created a comprehensive prenatal health care model that has almost tripled participation in its program during the first year of implementation and increased it again significantly during the second year. This decentralized pregnancy program has succeeded in getting all of the physicians offering obstetrical care in the district to serve low-income pregnant clients on a rotating basis. The new program provides pregnancy testing as well as financial screening services. Also, it has combined support services into one-stop-shopping clinics that include an innovative expansion of the Women, Infants and Children (WIC) Program of the U. S. Department of Agriculture. WIC food vouchers help attract clients into the prenatal care system and keep them coming. Enrichment of the duties of the public health nurse provides case coordination that pulls together the patchwork of medical and support services for the pregnant client. PMID- 1908584 TI - Effects of ritanserin on aversive classical conditioning in humans. AB - According to one formulation of the behavioural functions of 5HT, aversive conditioned stimuli mediate their behavioural and emotional effects through activation of 5HT projections from dorsal raphe nucleus to receptors of the 5HT2 family in amygdala and elsewhere. To test this theory in humans, groups of ten normal volunteers received placebo, the 5HT2 lc antagonist ritanserin (10 mg PO) and no pill. Ritanserin had no effect on skin conductance level, variability (spontaneous fluctuations) or habituation to a sequence of ten neutral tones. After a conditioning trial in which tone 11 was followed by an aversive white noise, skin conductance responses to a further ten tones were enhanced. This effect was abolished by ritanserin. The results indicate a selective involvement of 5HT2/lc receptors in modulating aversively conditioned skin conductance responses. PMID- 1908586 TI - Is battered women's help seeking connected to the level of their abuse? AB - A total of 289 abused women who sought assistance in several battered women's agencies were interviewed. Of these abused women, 70 percent reported a delay of more than a year in seeking help from the agency, even though many of them reported having experienced severe or life threatening abuse. There was no association between the severity of abuse and the time lapsed in seeking help from an agency, indicating that women exposed to severe, life-threatening physical abuse frequently delay help seeking. Increased attention to barrier to help seeking among battered women and approaches to increasing the accessibility of services for battered women seem warranted. PMID- 1908587 TI - Nutrition and health services needs among the homeless. AB - This review discusses nutrition and related health problems among homeless Americans, summarizes recent information, and identifies needs for services and future research. The nature of homelessness today provides a context for the discussion. Many homeless persons eat fewer meals per day, lack food more often, and are more likely to have inadequate diets and poorer nutritional status than housed U.S. populations. Yet many homeless people eligible for food stamps do not receive them. While public and private agencies provide nutritious food and meals for homeless persons, availability of the services to homeless persons is limited. Many homeless people lack appropriate health care, and certain nutrition related health problems are prevalent among them. Compared with housed populations, alcoholism, anemia, and growth problems are more common among homeless persons, and pregnancy rates are higher. The risks vary among homeless persons for malnutrition, nutrition-related health problems, drug and alcohol abuse, and mental illness. For example, among homeless persons, fewer heads of families than single adults are substance abusers, and mental illness varies in prevalence among single men, single women, and parents in homeless families. Homeless persons need improved access to food, nutrition, and health services. More nutrition education needs to be available to them and to service providers. Use of representative samples and validation of self-reported nutrition and health data will help future investigators to clarify the relationships between the characteristics of the homeless and their nutritional status. PMID- 1908588 TI - Financing geriatric programs in community health centers. AB - There are approximately 600 Community and Migrant Health Centers (C/MHCs) providing preventive and primary health care services principally to medically underserved rural and urban areas across the United States. The need to develop geriatric programs within C/MHCs is clear. Less clear is how and under what circumstances a comprehensive geriatric program can be adequately financed. The Health Resources and Services Administration of the Public Health Service contracted with La Jolla Management Corporation and Duke University Center on Aging to identify successful techniques for obtaining funding by examining 10 "good practice" C/MHC geriatric programs. The results from this study indicated that effective techniques included using a variety of funding sources, maintaining accurate cost-per-user information, developing a marketing strategy and user incentives, collaborating with the area agency on aging and other community organizations, and developing special services for the elderly. Developing cost-per-user information allowed for identifying appropriate "drawing card" services, negotiating sound reimbursement rates and contracts with other providers, and assessing the financial impact of changing service mixes. A marketing strategy was used to enhance the ability of the centers to provide a comprehensive package of services. Collaboration with the area agency on aging and other community organizations and volunteers in the aging network was found to help establish referral networks and subsequently increase the number of elderly patients served. Finally, development of special services for the elderly, such as adult day care, case management, and health education, was found to increase program visibility, opportunities to work with the network of services for the aging, and clinical utilization. PMID- 1908589 TI - The feasibility of collecting drug abuse data by telephone. AB - An evaluation was made of the use of telephone survey methods to collect illicit drug use data. Using data from a national survey that collects data by personal interviews, marijuana and cocaine use prevalence rates among households with telephones and those without were compared in order to assess coverage errors in telephone surveys. Drug use rates were substantially higher among households without telephones, with 24.9 percent of those living in households without telephones reporting use of marijuana in the past year, compared with only 9.4 percent of persons living in households with telephones. Trends in drug use were divergent, with substantial decreases in use occurring between 1985 and 1988 in households with telephones, but not in those without. National prevalence patterns and trends among households with telephone appear to be consistent with national patterns and trends in the total household population, because about 93 percent of the population lives in households with telephones. However, surveys conducted by telephone were found to produce underestimates of illicit drug use prevalence. In a 1988 national telephone survey, estimated rates of past year use were 5.2 percent for marijuana and 1.4 percent for cocaine. Comparable data from a personal visit survey (including only households with telephones and reedited and reweighted to control for differences in data collection protocols) were 8.0 percent for marijuana and 3.1 percent for cocaine use. Comparisons with several other telephone surveys collecting illicit drug use data showed similar results. Based on these results, researchers are advised to use caution in using telephone surveys to produce drug use prevalence estimates. PMID- 1908591 TI - Resting pulse rate of children and young adults associated with blood pressure and other cardiovascular risk factors. AB - Few researchers have investigated the resting pulse rate of children and young adults as a risk factor or indicator for subsequent cardiovascular morbidity in a representative sample of the total population. Data from the first National Health and Nutrition Examination Survey for persons ages 6-24 years revealed mean resting pulse rates that declined with age until ages 12-16, were higher in females than males, and in whites than blacks. At ages 12-17 and 18-24, blood pressure and body temperature showed consistent, independent, positive associations with pulse rate in whites. However, relatively little of the overall variation in pulse rate was explained by measured variables in multivariate regression analyses. Mother-child, age-specific correlation coefficients for pulse and blood pressure were generally positive. Further research is needed on the associations of resting pulse rate with sex, race, and blood pressure and with subsequent cardiovascular morbidity. PMID- 1908590 TI - Differences in hypertension prevalence among U.S. black and white women of childbearing age. AB - Hypertension and its sequelae complicate pregnancy and can result in poor perinatal outcomes. Overall, U.S. blacks are more likely to be hypertensive than whites, but the degree to which this is true among women of childbearing age (including teenagers) is unknown. Using data from the second National Health and Nutrition Examination Survey (NHANES II), the authors describe hypertension prevalence rates for 422 black and 2,700 white reproductive-age women. The authors present observed data and also predicted prevalence rates derived by modeling the odds of hypertension using logistic regression statistical techniques. They find that black-white differences in hypertension prevalence are negligible among teenagers, but they are pronounced in the older reproductive ages. They estimate that twice the proportion of black women relative to white are hypertensive during pregnancy. Their results suggest that differential rates of hypertension between black and white women may contribute to the persistent excess infant mortality among blacks, but conclusive results cannot be determined from these data. These data are also valuable for the design and evaluation of screening, intervention, and followup programs for hypertensive disease among young women. PMID- 1908592 TI - A study guided by the Health Belief Model of the predictors of breast cancer screening of women ages 40 and older. AB - In late 1987, a total of 852 Rhode Island women ages 40 and older were interviewed by telephone (78 percent response rate) to measure their use of breast cancer screening and to investigate potential predictors of use. Predictors included the women's socioeconomic status, use of medical care, a provider's reported recommendations for screening, and the women's health beliefs about breast cancer and mammography. The Health Belief Model guided the construction of the interview questions and data analysis. Logistic regression was used to identify leading independent predictors of breast cancer screening according to contemporary recommendations: reporting that a medical provider had ever recommended a screening mammogram (odds ratio [OR] = 18.77), having received gynecological care in the previous year (OR = 4.92), having a regular source of gynecological care (OR = 2.63), having ever had a diagnostic mammogram (OR = 2.32), and perceiving mammography as safe enough to have annually (OR = 1.93). The findings suggest that programs intended to increase the use of breast cancer screening should include "inreach" and "outreach" elements; inreach to patients with established patient-provider relationships, by assuring that physicians recommend screening to all eligible patients, and outreach to all eligible women, by helping them overcome barriers to effective primary care, and by promoting mammography, emphasizing its effectiveness and safety. The findings also suggest that socioeconomically disadvantaged women, who are less likely to be screened than other women, should become special targets of inreach and outreach interventions. PMID- 1908593 TI - Interpretative views on Hispanics' perinatal problems of low birth weight and prenatal care. AB - From a public health perspective, there is a need to recognize that Hispanics, and in particular Mexican Americans, are a very heterogeneous group. They represent all shades of acculturation, education, income, and citizenship status. As this minority group continues to increase in numbers, pertinent information about their perinatal health problems in the context of their sociocultural characteristics will be required. This review examines critically the recent literature related to low birth weight and prenatal care and suggests alternative ways to address these perinatal health issues. Low birth weight is examined in the context of the problem of intrauterine growth retardation and the potential mechanisms and consequences of different types of growth limitation in utero which have not been studied in this population. The use of prenatal care by Mexican American women and its association with birth weight is examined as an indication of maternal behavior or as a health care intervention. The implications for public health policy are discussed in relation to the identification, interpretation, and evaluation of these perinatal health issues in this minority population. PMID- 1908595 TI - Childhood injury prevention in a suburban Massachusetts population. AB - A controlled population-based study of a childhood injury prevention program in four suburban Massachusetts communities was able to demonstrate a 15.3 percent decrease in injury rates for children ages 0-5 years. A substantial improvement was seen in the relative risk for injury in the intervention as compared with control communities. The major intervention was a pediatric counseling program taking place within a context of various community education efforts. Process data on patient satisfaction and physician compliance, and educational and behavioral outcomes from previously reported studies, when combined with injury incidence data in this report, support the hypothesis that physician counseling may be an important factor in the favorable results observed in these suburban communities. These data also suggest that a decrease in injury incidence may be possible when interactive physician counseling takes place within the context of community education programs. A comprehensive strategy that includes technological, legislative, and educational activities is suggested as the optimal approach to childhood injury prevention. PMID- 1908594 TI - The association of prenatal nutrition and educational services with low birth weight rates in a Florida program. AB - Nutrition services and education, provided as components of normal prenatal care, have a key role in preventing preterm delivery and low birth weight (LBW). To determine the influence of these components on a woman's risk of having a LBW infant, the authors examined groups of patients who were receiving the services. Bivariate analyses were made of 9,024 prenatal charts of single births. Most women received nutrition education, prescriptions for nutrient supplements, screenings for anemia, and dietary assessments. A greater proportion of the women at high risk received the interventions than did women at lower risk. The presence of educational components and assays for anemia were associated with a lower risk of a LBW delivery in the total group and in the high risk groups. PMID- 1908596 TI - Followup study of possible HIV seropositivity among abusers of parenteral drugs in 1971-72. AB - Serum specimens obtained from a nationwide sample of parenteral drug abusers (PDAs) during the period 1971-72 had previously been screened for human immunodeficiency virus (HIV) antibodies. Some specimens were considered to be positive to both ELISA and Western blot (WB) analysis. These findings have been a topic of controversy, since HIV was not thought to have penetrated at-risk populations at such an early date. This study was a followup of those PDAs with apparent seropositivity to WB analysis. Of 10 persons followed, only one death (in 1985) was documented, and postmortem findings were inconsistent with HIV infection. Eight of the remaining PDAs were traced and found to be alive and well in 1989. Fresh specimens were obtained from the two persons with the strongest 1971-72 WB staining and were found to be both ELISA and WB negative on retesting. Their T-cell parameters were within normal limits. We concluded that the earlier WB results were most likely false positives and that definitive evidence of HIV infection in the U.S. addict population as early as 1971-72 is still lacking. PMID- 1908597 TI - Comparison of examination fees and availability of routine vision care by optometrists and ophthalmologists. AB - A national telephone survey of eye care practitioners shows that the average fee for routine eye examinations was less among optometrists than ophthalmologists. The average wait for the earliest appointment was 5 days for optometrists and 20 days for ophthalmologists. Weekend and evening appointments were also more obtainable among optometrists. The study did not determine what tests were included in the routine examination of each practitioner. Optometrists are licensed to use diagnostic drugs in all 50 States and prescribe therapeutic drugs for the treatment of ocular diseases in 25 States. Legislation that would update State laws permitting doctors of optometry to prescribe and use pharmaceutical agents for the treatment of eye diseases has been introduced in many of the remaining States. Supporters of bills permitting therapeutic pharmaceutical optometry contend that these changes would ensure the availability of quality eye care at significant savings, since optometric fees are generally lower than ophthalmological fees. In addition, it has been argued that optometrists are equitably distributed geographically and are more likely to have weekend and evening office hours, thus enabling increased patient access to eye care. When considering cost-effectiveness and accessibility, this study may provide information to those States considering changes in the scope of optometric licensure. PMID- 1908598 TI - Designing an AIDS information campaign to reach intravenous drug users and sex partners. AB - Intravenous drug users are currently the second largest group to have developed the acquired immunodeficiency syndrome in the United States and Europe. Clearly, health communication plays an important role in the development of AIDS prevention programs directed at IV drug users. However, few public information campaigns have been developed to reach IV drug users or their sexual partners. In a recent campaign directed at these groups, the selection of messages to be used was based both on theory and on research into multi-media public information campaigns. The attempt was made to communicate basic facts about AIDS etiology and prevention. This included information that needle sharing and unprotected sex could spread the human immunodeficiency virus (HIV) that causes AIDS, while bleaching needles and using condoms properly could reduce the risk of infection. A step-by-step diagram on how to bleach needles was provided. Posters, pamphlets, billboards, and out-reach workers were used to spread the word in inner-city neighbors, and coverage of the campaign was sought in the news media. Strategies incorporating practical and theory-based suggestions for future campaigns on IV drug use and AIDS are discussed. PMID- 1908599 TI - AHCPR begins new survey on cost and use of AIDS health, social services. PMID- 1908600 TI - Hypoxia following voluntary hyperventilation during exercise in man. AB - The importance of carbon dioxide in the control of ventilation during exercise was tested by emptying CO2 stores by voluntary hyperventilation. Healthy subjects were studied after 3 min hyperventilation down to an end-tidal PCO2 of about 20 mmHg on a background of steady exercise at 75 W. Control runs were performed when the hyperventilation was made isocapnic by the addition of CO2. Following hypocapnic hyperventilation, there was a period when ventilation fell below control and this was accompanied by a fall in end-tidal PO2 (minimum 48 mmHg) and oximeter reading (minimum 73%). Ventilation rapidly returned to baseline following isocapnic hyperventilation and hypoxia was not seen. A mathematical simulation suggested that brain PCO2 recovered more slowly than arterial PCO2 and that at the times that ventilation was depressed central chemoreceptor PCO2 would have been low. We conclude that CO2 provides a crucial drive for maintaining adequate ventilation during steady exercise and that the central chemoreceptor may be involved. PMID- 1908601 TI - A plague of plaques. PMID- 1908602 TI - [Health insurance and use of diagnostic related groups]. AB - One of the ways to improve measures aimed at population health protection may be the development of insurance medicine in our country. This is a system of curative and preventive measures realized through insurance payments made by citizens and on the basis of target payments by employers, employees and state grants. The international experience of insurance medicine indicates that the existing principle of grouping diseases according to the basic diagnosis no longer provides the effective use of resources and not precisely enough assess to the outcomes of hospital performance. The search of ways to solve this problem led to the necessity of using the method of assessing financial and economic activities of curative and preventive institutions on the basis of diagnosis related groups of diseases (DRG) which unite the cases of similar diseases having approximately the same technology of examination and treatment of patients and consequently the same cost of treatment. This system originated in the USA and is widely used in many countries of Western Europe. With the help of DRG system health institutions can acquire more full information on the results of treatment, costs of treatment and prospects for development. The introduction of DRG system permits to improve the financial and economic performance of institutions and to collaborate with organizations realizing health insurance programmes. PMID- 1908603 TI - [WHO has to beg for more funds]. PMID- 1908604 TI - Oral almitrine in treatment of acute respiratory failure and cor pulmonale in patients with an exacerbation of chronic obstructive airways disease. AB - The effects of oral almitrine bismesylate, a respiratory stimulant that acts on peripheral arterial chemoreceptors, was studied in patients with chronic obstructive airways disease and hypoxaemic cor pulmonale. Twenty three patients admitted to hospital with an acute exacerbation of ventilatory failure were randomised to receive either almitrine 100 mg twice a day reducing to 50 mg twice a day over 48 hours or placebo in addition to conventional treatment. On admission the mean (SE) values for blood gas tensions were PaO2 4.8 (0.3) and PaCO2 7.7 (0.3) kPa in the 12 patients who received almitrine and PaO2 4.9 (0.1) and PaCO2 7.6 (0.3) kPa in the 11 who received placebo. After three hours of oxygen therapy at 1 1/min there was a similar rise in PaO2 in both groups, 6.4 (0.2) kPa in those receiving almitrine and 6.6 (0.4) kPa in those receiving placebo. After 24 hours of oxygen therapy values of PaO2 were again similar at 6.3 (0.8) kPa and 6.7 (2.2) kPa respectively. Arterial blood gas tensions improved during the study in those who survived but no significant differences were apparent between the two groups. There were six deaths, five in the almitrine group and one in the placebo group. There were no differences between the groups in respiratory rate, results of spirometry, oxygen requirement, or degree of dyspnoea (on visual analogue scale). The results did not show any benefit from oral almitrine in patients with acute respiratory failure secondary to chronic obstructive airways disease. Plasma almitrine concentrations, however, were often below the optimum therapeutic range, suggesting impaired drug absorption. PMID- 1908607 TI - An unusual yet strongly conserved flavoprotein reductase in bacteria and mammals. AB - The recent determination of the amino acid sequences of the Bacillus megaterium cytochrome P-450 and the flavoprotein component of Salmonella typhimurium NADPH sulfite reductase revealed that these enzymes contain a flavoprotein moiety remarkably similar to mammalian NADPH-cytochrome P-450 reductase. The presence of this oxidoreductase in these very different enzymes suggests that this flavoprotein arose early in evolution and was utilized as an enzymological building block. The multi-domain structure of the reductase further suggests that it arose through a fusion of genes encoding simple flavin electron-transport proteins. PMID- 1908606 TI - The induction of divergent gonadotropin secretion in vitro by variations in luteinizing hormone releasing hormone pulse regimen. AB - The effects of luteinizing hormone releasing hormone (LHRH) pulse amplitude, duration, and frequency on divergent gonadotropin secretion were examined using superfused anterior pituitary cells from selected stages of the rat estrous cycle. Cells were stimulated with one of five LHRH regimens. With low-amplitude LHRH pulses (regimen 1) in the presence of potentially estrogenic phenol red, LH response in pituitary cells from proestrus 1900, estrus 0800, and diestrus 1,0800 were all significantly larger (P less than 0.05) than the other stages tested. In the absence of phenol red, responsiveness at proestrus 1900 was significantly larger than proestrus 0800, proestrus 1500, and estrus 0800 (P less than 0.01, 0.05, and 0.05, respectively); other cycle stages tested were smaller. No significant differences were observed between cycle stages for follicle stimulating hormone (FSH) secretion in the presence or absence of phenol red. Because pituitary cells at proestrus 1900 were the most responsive to low amplitude 4 ng LHRH pulses, they were also used to study the effects of LHRH pulses of increased amplitude or duration and decreased frequency. Increasing the amplitude (regimen 2) or the duration (regimens 3 to 5) increased FSH secretion; this effect was greatest with regimens 3 and 5. When regimens 3 and 5 were studied in pituitary cells obtained at proestrus 1500, FSH was significantly increased by both regimes, but most by regimen 5; furthermore, LH release was significantly reduced. When regimens 3 and 5 were studied in pituitary cells obtained at estrus 0800, FSH release was elevated most significantly by regimen 5. Thus, variations in LHRH pulse regimen were found to be capable of inducing significant divergence in FSH release from superfused anterior pituitary cells derived from specific stages of the estrous cycle. PMID- 1908605 TI - Aetiology of community acquired pneumonia in Valencia, Spain: a multicentre prospective study. AB - A year long multicentre prospective study was carried out in the Valencia region of Spain, to determine the cause of community acquired pneumonia. The study was based on 510 of 833 patients with pneumonia. Of these, 462 were admitted to hospital, where 31 patients died. A cause was established in only 281 cases--208 of bacterial, 60 of viral, and 13 of mixed infection. The most common microorganisms were Streptococcus pneumoniae (14.5%), Legionella sp (14%), Influenza virus (8%), and Mycoplasma pneumoniae (4%). There was a higher incidence of Legionella sp than in other studies. PMID- 1908608 TI - Selegiline (Eldepryl) for Parkinson's disease. PMID- 1908609 TI - Immunogenetics of the HLA system. AB - The study of the HLA system was primarily initiated to understand the basis for the histocompatibility between recipients and tissue donors. HLA typing methods are being continuously improved and biochemical and molecular typing, in particular, are expected to provide precise typing of the HLA system. Conventional HLA typing methods can define antigen specificities, while biochemical and molecular methods will provide direct allele typing that is based on the actual sequence polymorphism. The precise tissue typing will definitely improve the outcome of transplantation. Structural studies have revealed the highly polymorphic nature of the HLA system and given insight to understanding the molecular basis of the HLA polymorphism. One big immunological puzzle remaining to be answered is how T-cell receptor molecules recognize peptide antigen in conjunction with the HLA molecule. The crystallization of the T-cell receptor molecule, an experiment currently underway, will eventually reveal the structural basis of the trimolecular interaction. PMID- 1908610 TI - Lactobacillus casei subspecies casei endocarditis--a case report. AB - Lactobacillus sp., generally considered to be a harmless indigenous bacteria of the mucous membrane, occasionally causes serious infections. Lactobacillus endocarditis is a very rare disease, and no case has been reported in Korea. Gram positive bacilli were isolated from blood cultures of a 41-year-old man with clinically suspected subacute bacterial endocarditis. The patient had a dental procedure 3 months prior to the infection. The isolate was identified as L. casei subsp. casei based on the cultural characteristics and gas liquid chromatography of metabolic products. The patient was treated with ampicillin and improved. When Lactobacillus is isolated from the blood of an endocarditis patient, the significance should be seriously considered. PMID- 1908611 TI - Severe iatrogenic ergotism: incidence and clinical importance. AB - Ergot's derivatives are widely used to treat and prevent migraine and, associated with heparin, for the prevention of deep vein thrombosis. During a five-year period, 7 patients have been admitted in our hospital for severe vasospasm of one or several extremities due to ergot's derivatives. All patients presented with acute severe ischemia of the lower limb requiring iv infusion of vasodilator drugs. Ergotamine tartrate was the responsible drug in four patients and dihydroergotamine(DHE)-heparin in three patients. Intravenous administration of sodium nitroprusside (n = 6) relieved vasospasm in all but one of the patients within hours to days and no amputation was required. Ankle or great toe to arm systolic pressure index was normalized in the majority of the patients after treatment. A sympathectomy was performed in two patients which did not improve the clinical course. Distal necrosis developed in two patients (DHE-heparin). It is concluded that incidence of severe ergotism is less than 0.5/100,000/year in Geneva. This contrasts with the high prevalence (15%) of subclinical ergotism reported by others. No amputation was required in this series in spite of severe and prolonged vasospasms. Subclinical ergotism most probably precedes for weeks the onset of severe vasospasm, which calls for close monitoring of patients taking ergot's derivatives. PMID- 1908612 TI - Relaxation of sheep urethral muscle induced by electrical stimulation of nerves: involvement of nitric oxide. AB - Isolated smooth muscle preparations from the sheep urethra responded to electrical field stimulation with contraction when basal tension was low (5-6 mN), but with relaxation when the preparations were contracted with noradrenaline (NA), clonidine, or prostaglandin F2a. No relaxant response could be elicited in high K+ (124 mM) contracted preparations. Electrically induced relaxations had a threshold of less than 1 Hz and a maximum at 8 Hz. Both contractant and relaxant responses were abolished by tetrodotoxin, indicating that they were caused by transmitters released from nerves. The amplitude of the relaxant responses showed a highly significant correlation to the tension induced by noradrenaline. A coefficient (R/T) was calculated relating relaxation to noradrenaline-induced tension. In this way it is possible to separate the effect of drugs on muscle tension (non-specific effect) from their action on the electrically induced relaxation (specific effect). Chemical sympathectomy with 6-OHDA did not significantly modify the relaxant response to 6 Hz in noradrenaline contracted strips, as evaluated by the R/T coefficient. The electrically induced relaxation was not affected by hexamethonium, propranolol, phentolamine, muscarinic receptor blockade, cocaine, indomethacin, or methysergide. Both nifedipine and Bay K 8644 inhibited significantly the response induced by electrical stimulation, decreasing its maximum. Nifedipine, but not Bay K 8644, significantly reduced the level of tension induced by noradrenaline, and its effect, evaluated by the R/T coefficient, was an increase in the electrically induced relaxation, whereas Bay K 8644 had a significant inhibitory effect.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1908613 TI - Regulation of glutathione transferase P gene during hepatocarcinogenesis of the rat. PMID- 1908614 TI - Transcriptional and translational regulation of the expression of the l(2)gl tumor suppressor gene of Drosophila melanogaster. AB - By structural, biochemical and molecular genetic analyses, we have investigated the different mechanisms that control the expression of the lethal(2) giant larvae gene, a tumor suppressor gene of Drosophila melanogaster. Transcription of the l(2)gl gene is controlled by two highly identical promoters that result from the duplication of the 2.8 kb proximal portion of the gene. These two repeats are 96% homologous. Reverse genetic analysis has shown that each promoter can drive gene expression. In addition to the promoters, both repeats express two or three exons according to the pattern of splicing. The most distal exon in the second repeat is required because it contains the ATG initiating codon at the beginning of the open reading frame. The 3' untranslated region appears to contain motifs that specifically destabilize the transcript. Deletion of this region results in the formation of more stable mRNAs. The l(2)gl gene is characterized by an unusual codon usage that may reflect an enhanced translation efficiency by moderating the strength of pairing between codons and anticodons and may therefore increase the expressivity of this gene. Analysis of the spatio-temporal expression of the l(2)gl transcripts and proteins has shown that transcripts and proteins are produced ubiquitously during early embryogenesis, at a time when expression of the gene is required for preventing tumorigenesis. In the second half of embryogenesis, l(2)gl expression becomes restricted to tissues that do not show any phenotypic alteration in mutant animals. The l(2)gl protein exhibits two distinct intracellular localizations. It is preferentially found free in the cytoplasm but can become associated with the inner face of the plasma membrane where it is restricted to domains facing contiguous cells. In particular, the l(2)gl protein is absent from the basal and apical domains of the plasma membrane. The aim of the current research is directed towards understanding the functional relevance of the l(2)gl protein binding to the plasma membrane and its role in the control of cell proliferation and differentiation. PMID- 1908615 TI - Ca(2+)-dependent phosphorylation of synapsin I as a possible regulatory mechanism of neurosecretion. AB - Phosphorylation of homogeneous synapsin I isolated from human brain by Ca2+, phospholipid-dependent protein kinase (protein kinase C) from the same source was studied. The inhibitory effect of calmodulin on this process was demonstrated. The kinetics of activation of synapsin I phosphorylation by acidic phospholipids, phosphatidylserine and phosphatidylinositol, in the absence and presence of phosphatidylinositol-4,5-bisphosphate and diacylglycerol was compared. The proteolytic effect of degradation of the synapsin I molecule phosphorylated by Ca2+, calmodulin-dependent protein kinase II was revealed. No proteolysis of synapsin phosphorylated under similar conditions either by protein kinase C or cAMP-dependent protein kinase was detected. In view of the process specificity, the physiological significance of the observed effect is suggested. The inter relationship between two ways of neurosecretion regulation is discussed: an earlier known, conventional way, mediated by synapsin I phosphorylation by Ca2+, calmodulin-dependent protein kinase II, and another one, mediated by synapsin I phosphorylation by protein kinase C. The modulating role of polyphosphoinositides in the PK C-dependent way of regulation is considered. PMID- 1908616 TI - Inhibitory effect of curcumin and some related dietary compounds on tumor promotion and arachidonic acid metabolism in mouse skin. AB - Topical application of curcumin, the major yellow pigment in turmeric and curry, has a potent inhibitory effect on 12-O-tetradecanoylphorbol-13-acetate (TPA) induced tumor promotion in mouse skin. The structurally related compounds chlorogenic acid, caffeic acid and ferulic acid are less potent inhibitors. Curcumin is a potent inhibitor of TPA-induced ornithine decarboxylase activity and inflammation in mouse skin whereas chlorogenic acid, caffeic acid and ferulic acid are only weakly active or inactive. Curcumin is a potent inhibitor of arachidonic acid-induced inflammation in vivo in mouse skin, and this compound is also a potent inhibitor of epidermal lipoxygenase and cyclooxygenase activity in vitro. Although chlorogenic acid is only weakly active as an inhibitor of epidermal lipoxygenase activity and TPA-induced ear inflammation, it is more active than caffeic acid and ferulic acid. The inhibitory effects of curcumin, chlorogenic acid, caffeic acid and ferulic acid on TPA-induced tumor promotion in mouse skin parallel their inhibitory effects on TPA-induced epidermal inflammation and epidermal lipoxygenase and cyclooxygenase activities. Examination of the structural features of curcumin required for its biological activity indicate that free hydroxyl groups on the benzene rings are not required for inhibition of TPA-induced ornithine decarboxylase activity and inflammation in mouse skin. PMID- 1908617 TI - [Quantitative study of rat diabetic cataract, by the relaxation times of nuclear magnetic resonance]. AB - The prophylactic effects of a new aldose reductase inhibitor (ARI), FR74366 on streptozotocin-induced rat diabetic cataract were examined by means of proton nuclear magnetic resonance (1H-NMR) relaxation time. We compared the findings with the histological finding, and it was recognized that longitudinal and transverse relaxation times (T1, T2) were prolonged before the histological changes appeared. The ARI, FR74366, prevented histologic changes and had detected by the 1H-NMR method. The results showed that 1H-NMR could be useful in the early detection of human diabetic cataract and the evaluation of the effectiveness of anti-cataract agents, for example, AR inhibitors. PMID- 1908618 TI - Breath hydrogen excretion or plasma acetate levels during the lactulose tolerance test? AB - Since both acetate and hydrogen are produced by colonic bacterial fermentation, the clinical utility of the measurement of either parameter in nine subjects for the lactulose tolerance test was tested. The fasting plasma acetate concentration (mean +/- s.d., mmol/l) of 0.11 +/- 0.06 increased to peak levels between 150 min (0.23 +/- 0.12) and 180 min (0.23 +/- 0.09), both P less than 0.01, after ingesting 20 g lactulose. In one subject with previous gastrectomy and intestinal hurry, the peak was at 30 min. Mean post-lactulose acetate levels (0.21 +/- 0.09) were higher than fasting levels (P less than 0.03). Breath hydrogen excretion exhibited a similar trend. Indeed, a significant correlation (rs 0.39, P less than 0.01) was demonstrated between the acetate and hydrogen values. It is therefore concluded that patients for the lactulose breath test show fairly similar changes in plasma acetate and breath hydrogen excretion after lactulose ingestion. Either measurement could thus be used in assessing colonic fermentation in humans. PMID- 1908619 TI - Oral soft tissue malignancies in Ibadan, Nigeria. AB - Eighty-nine primary malignant neoplasms of the oral and oro-pharyngeal tissues excluding bone and salivary gland tissue were studied over a period of 21 years. They constituted 0.4% of the total number of neoplasms seen at the University College Hospital, Ibadan, over that period and contribute only a small proportion, in contrast to the widely held view that oral tumours are very common in Africa. Squamous cell carcinoma was the commonest type of lesion seen and the commonly affected sites were palate, gum (gingiva), tongue, lip and floor of mouth, in that order. The incidental overall male:female ratio is 2.4:1, and it varied for site and type of tumour. In general, the older male is most affected and the peak incidence of the malignancies occurred in the 51-60 years age group. PMID- 1908620 TI - Angiotensin converting enzyme inhibitors in cardiovascular and renal disease in Africans: a review. AB - The discovery and clinical availability of ACE inhibitor drugs is a triumph of rational drug development and a land-mark in biochemical pharmacology and hypertension research. The clinical pharmacological properties and haemodynamics of the clinically available drugs, captopril and enalapril, are reviewed, as is their therapeutic efficacy in African patients with essential and renal hypertension and chronic congestive heart failure. ACE inhibitors act as balanced arteriolar vasodilators and venular dilators and do not excite a reflex tachycardia in contrast to other vasodilator drugs. Their efficacy is, at least in part, dependent on plasma renin activity, which is low in Blacks and in Africans. Consistent with this, is the poor response to ACE inhibitor monotherapy of essential hypertension in controlled studies in Africans. However, the compensatory neuroendocrine activation which occurs in malignant hypertension, renal failure and congestive heart failure and concurrent diuretic therapy appears to enhance the clinical response to ACE inhibitors in African patients. PMID- 1908621 TI - Comparison of the urinary excretion time profile of amodiaquine in albino rabbits by fluorometric and high-performance liquid chromatographic methods. AB - Fluorometric and high-performance liquid chromatographic (HPLC) methods have been used to study the urinary excretion time profile of amodiaquine in albino rabbits after single oral (18.5 mg) and i.v. (9 mg) administration. There was no significant difference between the total mean values obtained for the two methods (P greater than 0.05). Although the HPLC method is more selective, one can still rely on the fluorometric method to measure urine concentrations of amodiaquine for therapeutic drug monitoring where toxicological conditions are not taken into consideration. PMID- 1908622 TI - The collodiaphyseal angle of the femur in adult Nigerians. AB - An investigation was conducted on 256 people, consisting of 138 men and 118 women in Ile-Ife, Oyo State, Nigeria, to determine the variation of collodiaphyseal angle (CDA) of the femur with the transverse and vertical diameters of the head of the femur, with the neck, upper shaft diameter and lower shaft diameter of the femur. The effects of sex and geographical location on CDA were also considered. It was observed that the mean CDA of the mean was greater than that of the women. The mean CDA of the right femur is generally greater than of the left femur in each sex. CDA significantly correlates negatively with the diameters of the head of the femur and with the diameters of the shaft, but positively with the neck. CDA exhibited regional variation in the female Nigerian population. Mean CDA of females in Ile-Ife, South-West Nigeria seemed greater than that of females in Calabar, South-East Nigeria. But mean CDA in the males is not different. CDA in Nigerians seemed greater than the CDA reported for the other countries and races. This might be due to different cultural habits of physique exhibited by the different races. PMID- 1908623 TI - Socio-cultural factors in adolescent septic illicit abortions in Ilorin, Nigeria. AB - One hundred and ninety-two adolescents (aged 12-18 years) with septic illicit abortions were interviewed to assess socio-cultural factors associated with illegally induced septic abortions at Ilorin, Nigeria. They were mostly unmarried schoolgirls who were ignorant of contraception. Inadequate parental supervision contributed largely to unplanned pregnancies, while poor economic state of these patients influenced the occurrence of illegal septic abortions. Wide-spread availability of an acceptable family-life education, with improved socio-economic state of the adolescents would most probably reduce the socio-cultural factors favouring illicit septic induced abortions in this community. PMID- 1908624 TI - Maternal weight and weight gain during pregnancy--can the arm circumference be used as surrogate? AB - A survey among pregnant Nigerian women attending an antenatal clinic showed a strong correlation between the arm circumference and weight. The sensitivity and positive predictive value of mid-arm circumference less than 23 cm for first trimester weight of less than 45 kg was 85.7% and 54.5% respectively. In the second trimester, these values for mid-arm circumference of less than 24 cm and weight less than 50 kg were 55.6% and 32.3% respectively. The specificity was high, ranging up to 99.4%. The value of the screening was found to be higher amongst primigravidas. Mid-arm circumference was however found to be insensitive for monitoring of weight gain during pregnancy. Strips based on this principle may be useful as a screening tool especially for low cadre health workers to identify pregnant women considered nutritionally at risk. PMID- 1908625 TI - The formation of acetate from ethanol with and without prior chlorpropamide intake in diabetic and non-diabetic subjects. AB - It has been suggested that raised post-ethanol plasma acetaldehyde levels, from inhibition of aldehyde dehydrogenase, underlie the liability to chlorpropamide, alcohol flushing (CPAF). We tested the hypothesis that acetate formation from acetaldehyde, the reaction catalysed by that enzyme, was also likely to be affected by chlorpropamide (CP) medication. In six healthy non-diabetic 'non flushers', fasting acetate (Ac +/- s.d. mmol/l) was 0.22 +/- 0.12, and increased by 0.47 +/- 0.14 to peak levels by 30 min after intake of 40 ml dry sherry, which increased plasma ethanol (mmol/l) levels to 10.2 +/- 6.0. After 5 days of CP (250 mg daily), fasting Ac (0.17 +/- 0.05) and increase to peak of Ac and ethanol after 40 ml sherry (0.56 +/- 0.12 and 8.9 +/- 7.2 respectively), were not changed (P n.s.). There was no correlation between Ac and ethanol at any time point. When the studies were repeated in five non-insulin-dependent diabetic 'flushers', both on regular CP medication and after 3 days without CP, there was again no significant difference in fasting and post-ethanol Ac levels between the two studies (fasting 0.18 +/- 0.04 v. 0.17 +/- 0.02, and increase to peak 0.62 +/- 0.13 v. 0.72 +/- 0.18, P n.s.). These results indicate that the conversion of ethanol to acetate is unaffected by CP medication, and furthermore that post ethanol acetate levels do not predict liability to CPAF. PMID- 1908626 TI - Tropical surgical abdominal emergencies: acute intestinal obstruction. AB - In a prospective evaluation of acute intestinal obstruction in emergency surgery, 3550 consecutive patients were studied. In the vast majority of patients (75%), obstruction was due to the external hernia, the inguinal hernia being by far the commonest type. However, the ascaris worm in children, volvulus of the sigmoid colon in adults, and intussusception in both children and adults, were significant causes of the disorder, and together accounted for 18% of the patients. Obstruction by the ascaris worm is easy to diagnose (by stool microscopy), and effective treatment (with antihelminthics) is readily available and cheap. A large number (90%) of the volvulus patients required resection for gangrene of the colon, thus arguing a strong case in support of laparotomy and inspection of the colon whenever feasible. A significant (41%) proportion of intussusception cases were adult, and in 33% of this group the lesion was associated with a tumour of the small bowel. The chief reason for death (10%) was late reporting to hospital. PMID- 1908627 TI - Influence of mucin on serum and connective tissue protein binding to Staphylococcus aureus isolated from nasal carriage and clinical sources. AB - A total of 89 Staphylococcus aureus strains were tested for [125I]-labelled fibronectin (Fn), type I (Cn-I), type II (Cn-II), type IV (Cn-IV) collagens and laminin (Lm) binding, and nasal carriage isolates (54 strains) demonstrated higher degree of interaction than clinical isolates (35 strains). Strains belonging to nasal carriage group, after preincubation with mucin demonstrated a significant decline in binding to Fn (39.4%), Cn-I (44.7%), Cn-IV (42.0%) and Lm (43.5%) compared with inhibition of binding of clinical isolates to Fn (13.3%), Cn-I (8.0%), Cn-IV (9.8%) and Lm (11.2%). S. aureus strain Nig-6 demonstrated a mucin concentration (in the range 0.01 to 100 mg/ml) dependent decrease of [125I] labelled serum and connective tissue protein binding. Mucin concentrations of 100, 150, 175 and 250 micrograms/ml when incubated with 10(9) cells, caused 50% displacement of [125I]-labelled Lm, Cn-I, Cn-IV and Fn uptake respectively. Mucin interaction with bacterial cells seems probably important in the pathomechanism of staphylococcal adhesion and colonization. PMID- 1908628 TI - Body temperature in apparently healthy African children under 10 years of age. AB - Body temperature was determined weekly for a period of 3 weeks in 346 healthy children aged 5 months to 10 years. Individual axillary temperatures in the 346 children ranged from 35.05 degrees C to 37.28 degrees C and fell into normal distribution curve. This study has thus determined normal body temperatures in Nigerian children and will serve as reference data for future comparison. PMID- 1908629 TI - Reduction of myocardial infarct size by poloxamer 188 and mannitol in a canine model. AB - Poloxamer 188 has been reported to inhibit thrombosis, decrease whole blood viscosity, and improve perfusion of damaged tissue. Mannitol has free radical scavenging capabilities that might contribute to myocardial salvage after ischemia. Because these agents appear to work in different ways, we studied their cardioprotective properties when they were used separately and in combination. After 75 minutes of left anterior descending coronary artery (LAD) occlusion, dogs received poloxamer 188 (48 mg/kg), mannitol (0.5 gm/kg), or both intravenously during an additional 15 minutes of LAD occlusion and for 45 minutes of reperfusion, whereas control dogs received an equal volume of saline solution. After surgery the animals were maintained for 24 hours and then killed. Areas of myocardial infarction (MI) and risk of infarction (R) were calculated by means of planimetric analysis of slices of myocardium stained with 1.5% triphenyltetrazolium and 0.5% Evans blue dye. The ratio of MI/R (mean +/- standard error of the mean) were: control, 25.6 +/- 1.8% (n = 10); poloxamer 188, 12.7 +/- 2.0% (n = 10); mannitol, 10.6 +/- 2.5% (n = 11); and poloxamer 188 plus mannitol, 8.0 +/- 4.1% (n = 10). Measurement of microvascular blood flow indicated a similar 86% to 91% reduction of blood flow to the area at risk in all treatment groups. Consequently both poloxamer 188 and mannitol appear to increase salvage of ischemic myocardium and a combination of the two may be more effective than either agent alone. PMID- 1908630 TI - Efficacy of slow-release nifedipine on myocardial ischemic episodes in variant angina pectoris. AB - To evaluate the efficacy of slow-release nifedipine (a single dose of 20 mg given at 10 P.M. or 2 doses of 20 mg at 10 P.M. and 6 A.M.) on ischemic episodes in patients with variant angina, a single-blind crossover study with ambulatory electrocardiographic monitoring was performed in 15 patients (13 men and 2 women, mean age 63 years). In all, there were 646 ischemic episodes detected with ambulatory electrocardiographic monitoring during the study period, and 618 episodes of them occurred during placebo periods with a circadian variation. Sixty-nine percent of the episodes in placebo periods were asymptomatic. The number of anginal attacks, nitroglycerin tablets taken, ST-segment elevation and the total ischemic duration significantly decreased during nifedipine therapy compared with results after the placebo therapy period, respectively (p less than 0.01 or 0.05). Twenty-eight ischemic episodes occurred during nifedipine therapy when the plasma level of nifedipine was low. Thus, asymptomatic ischemic episodes more frequently occur than symptomatic episodes and the administration of slow release nifedipine is highly effective in suppressing not only symptomatic but also asymptomatic myocardial ischemia in patients with variant angina. The timing of the administration of slow-release nifedipine is an important factor in suppressing ischemic episodes. PMID- 1908631 TI - Omega-3 fatty acids in health and disease and in growth and development. AB - Several sources of information suggest that man evolved on a diet with a ratio of omega 6 to omega 3 fatty acids of approximately 1 whereas today this ratio is approximately 10:1 to 20-25:1, indicating that Western diets are deficient in omega 3 fatty acids compared with the diet on which humans evolved and their genetic patterns were established. Omega-3 fatty acids increase bleeding time; decrease platelet aggregation, blood viscosity, and fibrinogen; and increase erythrocyte deformability, thus decreasing the tendency to thrombus formation. In no clinical trial, including coronary artery graft surgery, has there been any evidence of increased blood loss due to ingestion of omega 3 fatty acids. Many studies show that the effects of omega 3 fatty acids on serum lipids depend on the type of patient and whether the amount of saturated fatty acids in the diet is held constant. In patients with hyperlipidemia, omega 3 fatty acids decrease low-density-lipoprotein (LDL) cholesterol if the saturated fatty acid content is decreased, otherwise there is a slight increase, but at high doses (32 g) they lower LDL cholesterol; furthermore, they consistently lower serum triglycerides in normal subjects and in patients with hypertriglyceridemia whereas the effect on high-density lipoprotein (HDL) varies from no effect to slight increases. The discrepancies between animal and human studies most likely are due to differences between animal and human metabolism. In clinical trials eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in the form of fish oils along with antirheumatic drugs improve joint pain in patients with rheumatoid arthritis; have a beneficial effect in patients with ulcerative colitis; and in combination with drugs, improve the skin lesions, lower the hyperlipidemia from etretinates, and decrease the toxicity of cyclosporin in patients with psoriasis. In various animal models omega 3 fatty acids decrease the number and size of tumors and increase the time elapsed before appearance of tumors. Studies with nonhuman primates and human newborns indicate that DHA is essential for the normal functional development of the retina and brain, particularly in premature infants. Because omega 3 fatty acids are essential in growth and development throughout the life cycle, they should be included in the diets of all humans. Omega-3 and omega 6 fatty acids are not interconvertible in the human body and are important components of practically all cell membranes. Whereas cellular proteins are genetically determined, the polyunsaturated fatty acid (PUFA) composition of cell membranes is to a great extent dependent on the dietary intake.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1908632 TI - Oral nutrition in patients receiving home cyclic parenteral nutrition: pattern of substrate utilization. AB - Patients receiving cyclic home parenteral nutrition (PN) often have a significant oral caloric intake. This study describes the metabolic use of fuels, as assessed by indirect calorimetry, in eight stable, ambulatory, noncancerous, adult patients receiving glucose-based PN with (PN + oral) or without (PN only) a self selected oral intake. Patients' weight was 91 +/- 2% (mean +/- SE) of ideal body weight, and fat mass was 22 +/- 5 and 31 +/- 2% of actual body weight in males and females, respectively. Under the PN-only regimen, providing 104 +/- 5% of predicted basal energy expenditure (BEE), patients were in equilibrium for energy and nitrogen balances. Oral supplementation (absorbed oral intake 80 +/- 5% of BEE) was associated with positive energy and nitrogen balances but also with nearly continuous net fat synthesis. We conclude that the glucose-based PN + mixed oral regimen enables the patients to face the increased energy requirements of everyday ambulatory life but is not associated with an optimal body composition in long-term PN patients. PMID- 1908633 TI - Cysteine usage increases the need for acetate in neonates who receive total parenteral nutrition. AB - The addition of cysteine (as cysteine HCl) to a total parenteral nutrition (TPN) solution enhances calcium and phosphate solubility because cysteine lowers the pH of the solution. To determine whether adding cysteine to TPN solutions affected the acid-base homeostasis of infants and increased their need for acetate to obviate acidosis, we studied two groups of neonates--those receiving TPN before (group C) and after (group NC) the addition of cysteine. Measurements were made before and during the first 2 wk of TPN administration. We measured the pH of our standard TPN solution with and without the addition of cysteine. Serum carbon dioxide was significantly lower in group C despite a significantly greater intake of acetate in group NC. In the in vitro study the addition of cysteine to the TPN solution lowered the pH from 5.5 to 5.1. Newborns who received TPN solutions to which cysteine was added had lower serum carbon dioxide values and a greater need to receive acetate than did newborns who received TPN solutions without cysteine. PMID- 1908634 TI - ASCN/ASPEN Working Group on Standards for Aluminum Content of Parenteral Nutrition Solutions report. PMID- 1908635 TI - Improved neutrophil separation from anti-D-treated Rh(D)-positive whole blood by a discontinuous gradient method. AB - Neutrophil separation in Rh(D)-positive whole blood with a discontinuous gradient method (Ficoll 1077-1119 and sodium diatrizoate) was improved by adding anti-D reagent to ethylene diaminetetraacetic acid anticoagulated blood (1 drop/mL). The mean yield was raised more than two times (x2.6) without red blood cell contamination. Anti-D reagent did not impair neutrophil viability, purity, nitroblue tetrazolium-formazan production, or shape change response to N-formyl methionyl-leucinyl-phenyl-alanine. PMID- 1908636 TI - A variant form of thrombasthenia. AB - We encountered two siblings with abnormal bruising since infancy. Studies revealed functional platelet defects characterized by a lack of platelet aggregation and adenosine triphosphate release on exposure to adenosine diphosphate and collagen as well as variable responses with ristocetin (at concentrations of less than or equal to 1.25 g/L) and arachidonic acid. In addition, little or no platelet aggregation was observed after exposure to hexadimethrine bromide (Polybrene), the calcium ionophore A23187, and the thromboxane/endoperoxide analogue U46619. The membrane proteins IIIa and Ib were present, as determined with monoclonal antibody testing, and no platelet associated IgG was found. Platelet analysis with routine electron microscopy and ultrastructural cytochemistry revealed normal morphologic features and no deficiencies in the number of alpha granules dense bodies and other organelles. The platelet abnormality may represent a new variant of thrombasthenia. PMID- 1908637 TI - Galactose metabolism and reproductive history in women with type 1 neurofibromatosis. AB - To explore a possible relationship between neurofibromatosis and abnormalities of galactose metabolism, we examined the activity and characteristics of red cell galactokinase and galactose-1-phosphate uridyl transferase in 14 white women with type 1 neurofibromatosis and in 28 control women. Women with NF1 had a significantly lower activity of galactokinase and were more likely to have the 3 band pattern on electrophoresis of their transferase enzyme known as the Duarte variant. In addition, we found that women with NF1 were more likely to have reproductive histories suggestive of hypogonadism, including irregular menses, infertility, ovarian cysts, and early menopause. We conclude that abnormalities of galactose metabolism may be linked to abnormalities of both germ cell and neural crest development. PMID- 1908638 TI - The Lazarus Project: the politics of empowerment. AB - The problems associated with institutionalized care of the frail elderly are complicated and require interdisciplinary problem solving. This paper explains the conceptual framework and initial implementation of the Lazarus Project, a pilot project in a nursing home that offers an alternative governing philosophy for residential living. The framework is a community model based on democratic governance, which empowers those who work and live within the nursing home facility. Implementing a community model in an institution is a political process that requires an awareness of power relationships and structures. Strategies for institutional change are directed at alteration of the hierarchical power structures so that power is shared and decision making collaborative. PMID- 1908639 TI - Cromakalim and pinacidil dilate small mesenteric arteries but not small cerebral arteries. AB - Small elevations in external K+ hyperpolarize and dilate small cerebral arteries. The hyperpolarization and dilation to K+ are blocked by barium (less than 0.1 mM). Since membrane hyperpolarization appears to be an important mechanism for dilation of these small cerebral arteries, we investigated the effects of the hyperpolarizing vasodilators, cromakalim and pinacidil, on isolated pressurized rat cerebral arteries (diameter of 158 +/- 5 microns at 50% of the systolic blood pressure). Cromakalim and pinacidil, which are potent relaxants of a variety of muscle types, were without effect on posterior cerebral arteries at concentrations that completely dilate similarly sized rat mesenteric arteries (diameter 134 +/- 6 microns at 50% of the systolic blood pressure). The mesenteric artery dilation to cromakalim and pinacidil was reversed by glibenclamide. However, unlike the cerebral arteries, mesenteric arteries did not exhibit a barium-sensitive dilation to external K+. Thus it appears that there may be differences in the types of K+ channels that are activated by dilating mechanisms in small cerebral and mesenteric arteries. PMID- 1908640 TI - Endothelin effects in isolated, perfused lamb lungs: role of cyclooxygenase inhibition and vasomotor tone. AB - We have determined the sites of action of endothelin-1 (ET) in the lamb pulmonary circulation. The influence of cyclooxygenase inhibition and baseline vasomotor tone on ET effects was also studied. Lungs of 14 lambs (6-9 wk of age, 12.1 +/- 0.6 kg body wt) were isolated and perfused with blood. Group I lungs (n = 5) were untreated, group II lungs (n = 5) were treated with indomethacin to inhibit cyclooxygenase, and group III lungs (n = 4) were treated with indomethacin and a thromboxane A2 analogue, U-46619, to elevate vasomotor tone. All lungs were perfused with constant flow in zone 3, with left atrial and airway pressures being 8 and 6 cmH2O, respectively. We measured pulmonary arterial pressure and, by the micropuncture servo-null method, pressures in 20- to 50-microns diameter subpleural venules, both before and after each dose of ET was infused (50, 100, 250, and 500 ng/kg). Group I lungs, with high baseline vasomotor tone, exhibited a biphasic response to ET; 50-100 ng/kg of ET dilated both arteries and veins, whereas 500 ng/kg of ET constricted both arteries and veins. In group II lungs with low vasomotor tone, all doses of ET caused constriction of arteries only. In group III lungs (indomethacin treated with elevated vasomotor tone), 50-100 ng/kg of ET caused dilation of arteries and veins, whereas 500 ng/kg of ET induced constriction, this time only in arteries. We conclude that ET has both dilator and constrictor effects in arteries and veins of isolated, perfused lamb lungs. ET-induced arterial and venous dilation is dependent on initial vasomotor tone but not on cyclooxygenase metabolites.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1908641 TI - Effects of 12-HETE on isolated dog renal arcuate arteries. AB - 12-Hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE) is one of the major noncyclooxygenase eicosanoids formed in vascular tissue. The vasoactive effects of the cytochrome P-450 product, 12(R)-HETE and the lipoxygenase product, 12(S) HETE, on isolated, perfused renal arcuate arteries of the dog were investigated using videomicroscopy. R and S refer to stereoconfiguration of the hydroxy group at the twelfth position of this fatty acid structure. Cumulative doses of 12(R) HETE produced a concentration-dependent vasoconstriction (n = 9) with a threshold dose of 10(-9) M. At a concentration of 3 x 10(-7) M, 12(R)-HETE reduced vascular diameter by 63 +/- 8 microns (from 306 +/- 17 microns), which was 37 +/- 6% of the maximal vasoconstrictor response to norepinephrine (10(-6) M). The effects of 12(R)-HETE were not altered by indomethacin (10(-6) M, n = 8). The vasoconstrictor response was associated with depolarization of vascular smooth muscle from -47 +/- 1 (15 cells) to -32 +/- 1 mV (12 cells). 12(S)-HETE was also a vasoconstrictor (n = 6), but the threshold concentration for vasoconstriction was 10(-8) M. Small renal arteries obtained from ischemic-injured, but not normal, kidneys produced a metabolite when incubated with arachidonic acid, which coeluted with a 12-HETE standard using reverse-phase high-pressure liquid chromatography. The rate of synthesis of this 12-HETE-like metabolite by renal arteries obtained from ischemic-injured and normal kidneys averaged 1.2 +/- 0.4 (n = 9) and 0.1 +/- 0.1 (n = 7) pmol.h-1.mg tissue-1, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1908642 TI - 2,5-anhydro-D-mannitol acts in liver to initiate feeding. AB - We determined the site at which the fructose analogue 2,5-anhydro-D-mannitol (2,5 AM) acts to increase food intake in rats. Rats began eating sooner and ate more food during hepatic portal than during jugular infusions of 2,5-AM (50, 100, or 150 mg/h). After rats were intubated with 2,5-[14C]AM (1.15 microCi in 200 mg/kg), significant quantities of radioactivity were found in liver but not in brain. Hepatic vagotomy prevented the eating response to 200 mg/kg 2,5-AM without altering the effect of the analogue on plasma fuels. These results indicate that low doses of 2,5-AM act in the liver to increase food intake and suggest that the signal for feeding generated in the liver is transmitted to the brain through the hepatic vagus nerve. Taken together, this work provides the strongest evidence to date that a signal initiating feeding behavior originates in the liver. PMID- 1908643 TI - Sodium-dependent magnesium transport across in situ perfused rat placenta. AB - Placentas of anesthetized rats were perfused in situ on the fetal side to study mechanisms of Mg2+ transport. The perfusate was a Mg(2+)-free Krebs-Ringer, and the unidirectional transfer of Mg2+ from maternal plasma to this Ringer was compared with that of 45Ca and 51Cr-EDTA, the latter being employed as a paracellular diffusional marker. Placental perfusion with amiloride (0.5 mM) or ouabain (1 mM) both rapidly (4 min) reduced maternal-fetal clearance (Kmf) for Mg2+ but had no effect on Kmf for 45Ca. In contrast, perfusion of the carbonic anhydrase inhibitor acetazolamide (1 mM) did not affect Kmf for Mg2+ or 45Ca. Placental perfusion with a Na+-free Ringer reduced Kmf for both Mg2+ and 45Ca, although the latter response was delayed. Kmf for 51Cr-EDTA was increased by amiloride and was unaffected by perfusion of ouabain, acetazolamide, or Na+-free Ringer, indicating that the effects of these treatments on Kmf of Mg2+ do not reflect nonspecific effects on placental permeability. These data suggest that maternal-fetal transfer of Mg2+ across the perfused rat placenta is Na+ dependent. PMID- 1908644 TI - Microdialysis of norepinephrine into preoptic area of guinea pigs: characteristics of hypothermic effect. AB - This study was designed to characterize the previously described hypothermic action of norepinephrine (NE) microdialyzed into the medial preoptic area (MPO) of conscious guinea pigs. To this end, the effects on core temperature (Tco) of isotonic pyrogen-free saline (PFS), hypotonic PFS, inactive (oxidized) NE (hypertonic), 5-hydroxytryptamine (5-HT, 10 and 20 micrograms/microliter), PFS with or without 2.4 mM Ca2+, 10 micrograms/microliters NE with Ca2+, and various doses of NE (0.05-60 micrograms/microliters) were compared in a series of studies at an ambient temperature (Ta) of 24 degrees C. The Tco responses to 10 micrograms/microliters NE in a cold (15 +/- 2 degrees C) and a warm (31 +/- 1 degrees C) Ta and during the night in the dark in Ta 24 degrees C were also measured. Bromophenol blue (0.2%) was microdialyzed to assess the extent of diffusion of these dialysates. A stain was found in the MPO, which increased in density but did not spread beyond this region over 3 h of continuous microdialysis. Neither PFS nor the hypotonic and hypertonic solutions had any obvious effect on Tco. Similarly, neither dose of 5-HT evoked a thermal response. Ca2+ added to either PFS or NE did not alter the usual Tco responses to these two solutions. NE induced dose-dependent hypothermia in Ta 24 degrees C. NE microdialyzed in Ta 15 degrees C also produced Tco falls, but these responses were smaller than those in 24 degrees C. NE had no effect in the warm Ta. During the night, NE elicited similar Tco falls, but their recoveries after dialysis ended were slower than during the day.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1908645 TI - A5 noradrenergic unit activity and sympathetic nerve discharge in rats. AB - Unit recording experiments were designed to determine whether A5 noradrenergic neurons contribute to the generation of the splanchnic sympathetic nerve discharge (SSND) of halothane-anesthetized rats. Neurons (presumed A5 cells) were selected on the following bases: location in the ventrolateral tegmentum rostrolateral to facial nucleus (FN), antidromic (AD) activation from thoracic spinal cord, and complete inhibition by clonidine (10-15 micrograms/kg iv). These cells (n = 59) had low rates of spontaneous firing (1.4 +/- 0.2 spikes/s) and slow conduction velocities (2.6 +/- 0.2 m/s). The AD activation of seven of eight neurons was abolished within 1 h after intraspinal microinjection of 6 hydroxydopamine (4 micrograms), but the drug failed to affect the AD responses of eight sympathoexcitatory cells located caudal to the FN (control cells). The terminal fields of 16 A5 area neurons were found in the intermediolateral cell column of the spinal cord. Most neurons (63%, 37/59) were inhibited by raising arterial pressure and by train stimulation of the aortic depressor nerve (ADN, 47%, 9/20). A few cells responded to ADN stimulation but not to arterial pressure elevation or vice versa. The discharge of the cells was correlated to the SSND and preceded a peak of SSND by 69 +/- 6 ms (12/29 in intact and 3/9 in debuffered rats). We conclude that 40% of A5 cells may have a visceral vasomotor sympathoexcitatory function. PMID- 1908646 TI - Developmental changes in adenylyl cyclase and GTP binding proteins in brown fat. AB - During the perinatal period, norepinephrine (NE)-stimulated adenylyl cyclase activity increased in interscapular brown adipose tissue (IBAT) membranes and then declined to adult levels by 23 days postpartum. The developmental patterns of NE- and NaF-stimulated activities were identical, indicating that the developmental increase in transmitter-stimulated activity resulted from the increased interaction of alpha-subunit of guanine nucleotide-binding stimulatory protein of adenylyl cyclase (Gs alpha) with the catalytic subunit (C). This increased Gs alpha-C interaction was the result of an increase in Gs alpha specific activity, as assessed in cyc- reconstitution assays, as well as an increased C activity, as assessed by forskolin-Mn(2+)-stimulated adenylyl cyclase activity. Although adenylyl cyclase activity increased during the perinatal period, total Gs alpha levels significantly declined because of the loss of the small-molecular-mass form of Gs alpha. Thus the ratio of large to small form of Gs alpha increased threefold and might have contributed to the perinatal increase in activity. Gi alpha-like proteins, as assessed by pertussis toxin-catalyzed [32P]ADP ribosylation, declined dramatically after birth. However, this loss of Gi alpha did not contribute to developmental changes in adenylyl cyclase activity because pertussis toxin treatment failed to alter NE-stimulated activity. In contrast to G alpha subunits, there were no changes in membrane levels of G beta subunits. PMID- 1908647 TI - DNA synthesis is reduced in selected fetal tissues during prolonged hypoxemia. AB - The effects of 24 h of reduced maternal uterine blood flow (RUBF) on relative DNA synthesis rates in different tissues and on blood glucose and lactate concentrations were studied in fetal sheep. In six sheep, RUBF was induced for 24 h, whereas in another six sheep (controls), uterine blood flow was not reduced. To estimate DNA synthesis rate, [3H]thymidine (1 mCi/kg) was injected intravenously into each fetus 8 h before the end of the 24-h experimental period. Fetal arterial oxygen saturation decreased from 59.1 +/- 3.3 to 25.7 +/- 5.6% after 1 h of RUBF and remained significantly reduced for the duration of the experiment. Fetal blood lactate concentrations were significantly increased by RUBF from 14.3 +/- 6.5 to 57.8 +/- 12.4 mg/dl at 1 h and remained elevated, whereas fetal blood glucose concentrations were not affected. A 24-h period of RUBF did not significantly alter fetal body weights, tissue weights, tissue-to body weight ratios, or tissue DNA content. Over the last 8 h of the 24-h experimental period, RUBF was found to significantly reduce the relative rate of DNA synthesis (as assessed by [3H]thymidine incorporation into DNA) in the lung (104.7 +/- 26.6 vs. 17.1 +/- 3.1 dpm/micrograms DNA), quadriceps muscle (92.8 +/- 20.7 vs. 14.4 +/- 5.3 dpm/micrograms DNA), and thymus gland (87.5 +/- 7.1 vs. 32.9 +/- 12.2 dpm/micrograms DNA). Relative DNA synthesis rates in the fetal liver, kidney, small intestine, cerebral cortex, cerebellum, placenta, thyroid gland, and adrenal gland were not significantly affected by RUBF. In this study, we have shown that DNA synthesis was greatly reduced in selected fetal tissues (lung, quadriceps muscle, and thymus gland) by a 24-h period of RUBF, although it is not known why a reduction was only observed in these tissues. PMID- 1908648 TI - The cost of medical care for injuries to children. AB - STUDY OBJECTIVES: To estimate the mean cost of initial medical treatment for a variety of injury types and injury causes and project the national cost of initial medical care for injuries to children. DESIGN: We combined injury incidence data from the Massachusetts Statewide Childhood Injury Prevention Project (SCIPP) with a claims data set (1987 charges) from the Health Data Institute, Lexington, Massachusetts. SETTING AND STUDY POPULATION: SCIPP incidence data were obtained from hospital emergency department and inpatient facilities for a population of 87,000 Massachusetts children 0 to 19 years old between 1979 and 1982. Health Data Institute charge data for children were derived from insurance claims for 3% of all privately insured patients throughout the United States. RESULTS: The estimated mean cost of initial hospitalization for injury was $5,094, while ED care was $171. Projected annual cost for initial medical care of injury to children for the nation was $5.1 billion, which was about equally divided between cases seen in EDs and those requiring inpatient care. Although there was little difference in mean cost between the genders, mean cost increased with age. Because of both a higher injury incidence and a greater mean cost per injury, the projected initial cost of injuries to teenagers 15 to 19 years old was much higher than that of younger children. CONCLUSION: Expenditures for medical care of injured children, particularly adolescents, are great. The prevention of childhood injuries should become a higher priority in the United States. To improve the quality of national estimates of the incidence and cost of injury, a national surveillance system for nonfatal injuries should be developed. Such a system should include information on the major causes of injury and their costs. PMID- 1908649 TI - ABO and Rh(D) blood group frequencies in the Ards Peninsula, northeastern Ireland: evidence for the continuing existence of a major politico-religious boundary. AB - Data are presented on the ABO and Rh(D) frequencies of 1685 individuals living in the Ards Peninsula, northeastern Ireland. Previous investigations based on surname analysis and linguistic studies showed a basic north-south population divide that could be traced back at least to the early seventeenth century. The current survey indicates the continuation of this divide, which is coincident with known patterns of religious persuasion. PMID- 1908651 TI - [Clinical studies on preoperative continuous intra-arterial chemotherapy in the treatment of malignant soft tissue tumors]. AB - Preoperative continuous intra-arterial chemotherapy combined with surgery in the treatment of malignant soft tissue tumors has been used since 1971 in our clinic. We treated thirty-eight patients, and twenty-five of them underwent preoperative intra-arterial chemotherapy and surgery. The diagnoses were liposarcoma (5), synovial sarcoma (4), rhabdomyosarcoma (2), angiosarcoma (2), malignant schwannoma (2), malignant lymphoma (2) and 8 other types of tumors. From the standpoint of local failures, there was only one recurrent case. Eighteen patients are alive now without evidence of disease. The 10-year cumulative survival rate for cases treated with intra-arterial chemotherapy was 69.5%, as compared with 24.9% of cases without intra-arterial chemotherapy. Therefore we conclude that preoperative continuous intra-arterial chemotherapy is a very effective method in the treatment of malignant soft tissue tumors. PMID- 1908650 TI - [Effect, recurrence and prognosis of intra-arterial infusion chemotherapy with anticancer agents for advanced breast cancer--especially, the significance of tumor blood vessels]. AB - Between January 1977 and March 1991, 86 patients of Stage III and Stage IV breast cancer were treated by intra-arterial infusion chemotherapy (IAIC) in Sapporo Medical College. The 5- and 10-year overall survival rates of Stage III b were: infusion group 53.1% and 53.1%, non infusion group 50.1% and 16.7%, respectively. A significant difference was seen in the 10-year survival rate (p less than 0.05). The 5- and 10-year overall survival rate of Stage III b histologically effective group was 67.3% and non-effective group 31.8%. A significant difference was seen between these two groups (p = 0.0241). A significant difference was seen between n2 positive Stage III b infusion group and non-infusion group in 7-year survival rate (p less than 0.01). The ischemic effect on tumor cells by degeneration changes of the blood vessels was important for the histological effect. Pre-operative angiography helped in the choice of anticancer agents. The sufficient adjuvant chemo-endocrine therapy will assure a good prognosis for IAIC treated Stage III b breast cancer patients. PMID- 1908652 TI - [Continuous hyperthermic peritoneal perfusion (CHPP) therapy in advanced gastric cancer]. AB - In CHPP therapy for advanced gastric cancer, a perfusate containing 20 mg CDDP and 8 mg MMC in 1,000 ml physiologic saline warmed at 47 degrees C was infused at a constant rate of 200 ml/min into the pouch of Douglas. The intraperitoneal temperature at the supra-pancreatic region was around 39.0 degrees C. To obtain a more stable and higher intraperitoneal temperature, the infusing rate was increased to 400 ml/min. This yielded a 3 degrees C higher temperature (42 degrees C) at the same measuring site. However, the temperature recorded at various intraperitoneal sites did not always reach such an effective range. The maximal plasma concentrations of MMC determined during CHPP at the 200 and 400 ml/min infusion were 0.09 +/- 0.03 and 0.11 +/- 0.03 microgram/ml, and those of CDDP 1.6 +/- 0.4 and 1.7 +/- 0.3 microgram/ml, respectively, all of which were not significantly different. When an intraperitoneal dosage of 20 mg MMC was given to 3 patients, the portal venous blood, at 10 min after the administration, produced a 1.7 times higher concentration of the agent than did the peripheral venous blood. This discrepancy between the two concentrations was much smaller than found by other investigators in animal experiments. PMID- 1908653 TI - [Circadian-rhythm of tumor growth in non-vascularized tumor]. AB - Circadian-Rhythms of tumor growth rates of Walker-256 implanted in the dorsum side of hind paw of Wistar rats (Male 5-6 weeks age) were observed. Tumor size was measured at 7 A.M. and 7 P.M. The tumor growth rate was determined by the following method. Rday = T (P.M.)/T (A.M.). Rnight = T (A.M.)/T (previous P.M.). Rday and Rnight: Tumor growth rate during day and night, respectively. T: Tumor size. The tumor growth rate, for those less than 750 mm3 in size and in which tumor vessels did not form yet, was 0.10 +/- 0.5 on Rday, 0.29 +/- 0.12 on Rnight (p less than 0.05). Tumors of more than 1,500 mm3 forming tumor vessels did not show a significant difference in the degree of the tumor growth rate (Rday: 0.14 +/- 0.07; Rnight: 0.212 +/- 0.05) (p greater than 0.05). Tumors in which vessels were injured and showed microvascular disturbance due to MMC (A. i) or thermochemotherapy using warmed physiological saline injected into tumor vessels after chemotherapy, were damaged on Rday and enhanced on Rnight for 3-7 days after these kinds of treatment. The tumor in unformed tumor vessels or damaged types showed, rapid size increase at night. Therefore, the Circadian-Rhythm tumor vessels in microtumor or damaged tumor may be treated with antimetabolic agents such as 5-FU at night for inhibition of microtumor or micrometastatic tumor. PMID- 1908654 TI - [Hepatic arterial infusion chemotherapy and loco-regional treatment and irradiation of pancreas tumor in non-resectable pancreas cancer with liver metastases]. AB - This study seeks to evaluate arterial infusion chemotherapy and radiotherapy for non-resectable pancreatic cancer with liver metastases. Arterial infusion to the liver was performed in 24 patients, 15 of whom received arterial infusion to the pancreas and 9 of whom underwent irradiation for pancreas tumor (40-50 Gy). However, arterial infusion to the liver alone did not prolong survival, but loco lesional therapy for the pancreas tumor improved quality of life and resulted in good local control. The survival of the two treatment groups (arterial infusion to the liver combined with loco-regional treatment to the pancreas versus systemic chemotherapy) was statistically different (median 7 months versus 3 months, p less than 0.01). Arterial infusion to the pancreas decreased liver metastases as the first site of failure. These results suggested that arterial infusion to both liver and pancreas combined with irradiation for the pancreas tumor are effective in increasing survival time and improving the quality of life. PMID- 1908655 TI - [Clinical evaluation of intra-peritoneal hyperthermic perfusion under hypothermic general anesthesia for advanced gastric cancer]. AB - Right after surgery, intra-peritoneal hyperthermic perfusion (IPHP) was performed under hypothermic general anesthesia for 41 gastric cancer patients with peritoneal dissemination or serosal invasion. The control group consisted of 40 patients given surgery alone. With respect to the direct antitumor efficacy of IPHP, there were no cancer cells in the peritoneal lavage from Douglas' pouch and, ascitic effusion disappeared in all patients with peritoneal dissemination. The 1- and 3-year survival rates for the IPHP group were 68% and 39%, whereas those of the control group were 30% and 0%, respectively. The survival rates for the IPHP group were better than those for the control group, with a statistically significant difference of p = 8.1 x 10(-7). As to prevention of recurrence, the incidence of peritoneal dissemination for the IPHP group was lower at p = 0.002 than the control group. PMID- 1908656 TI - [Prevention of peritoneal dissemination after colorectal surgery--significance of MMC administration in abdominal cavity]. AB - Peritoneal lavage cytology during surgery was done in 287 patients with colorectal cancer. Positive cytologic specimens were obtained from 21 patients. Of 13 patients who had free cancer cells in peritoneal cavity but no peritoneal dissemination macroscopically, 5 patients received intraperitoneal administration of 20 mg of MMC dissolved in 500 ml of saline. Peritoneal dissemination occurred in 0/5 (0%) of the MMC treated group and in 5/8 (63%) of the untreated group (p less than 0.05). Our results indicate that intraperitoneal administration of MMC (20 mg) is an effective method of preventing peritoneal dissemination after resection of colorectal cancer. PMID- 1908657 TI - [Effect of intraarterial noradrenaline-induced hypertensive chemotherapy of hepatic metastasis in gastric cancer]. AB - Four patients with hepatic metastasis of gastric cancer (one synchronous, three metachronous), received intraarterial noradrenaline-induced hypertensive chemotherapy. The outlet of the indwelling catheter was placed in the proper hepatic artery in two patients, in the thoracic aorta in one patient and in both places in one patient. When the systolic blood pressure rose 50 percent above the level in the untreated state, mitomycin C via the catheter was administered for 10 minutes. Partial remission was found in 2 patients, NC in one patient and PD in another. One patient showing PR died of a relapse of hepatic metastasis 8 months after treatment. Another patient with PD died of multiple bone metastases after 12 months. The two other patients are alive 19 months after treatment. Intraarterial noradrenaline-induced hypertensive chemotherapy is one of the useful treatments of choice for hepatic metastasis of gastric cancer. PMID- 1908658 TI - [Continuous infusion chemotherapy using an infusional port in colorectal cancer with liver metastases]. AB - Chemotherapy for colorectal cancer with liver metastases following surgical operation for primary tumor should be selected following surgical intervention. Continuous infusion chemotherapy using an infusional port was selected for unresectable metastasis due to colorectal cancer in our department. The catheter was placed in the hepatic artery through a gastroduodenal by operative procedure. 5-fluorouracil (5-FU) and mitomycin C (MMC) were used as chemotherapeutic agents. After MMC was given at 10 mg/body by bolus, administration of 5-FU was continuously infused at 250 mg/day for 2 weeks, followed by a 2-week interval. Drug administration was done by implanted pump hepatic arterial infusion. Seventeen of the patients with liver metastasis underwent this chemotherapy from 1986 through 1990. Results of the infusion chemotherapy were as follows. Value of serum CEA decreased until two courses were given in all cases. In 11 cases, the tumor size on CT was remarkably smaller. In these patients, however, there were many complications due to the catheter used for catheter replacement, drug leakage, drug extravasation and so on. We concluded that although this chemotherapy was very effective, the method should be improved in terms of the material, the location of catheter tip and the like. PMID- 1908659 TI - [Intra-arterial infusion chemotherapy using an implantable reservoir in the treatment of hepatic metastases in colorectal cancer]. AB - With colorectal cancer, the therapeutic outcome for multiple hepatic metastasis extending to the bilateral lobe, even when various chemotherapies are administered, is extremely poor. For multiple hepatic metastases at our clinic, from November, 1985, through February, 1991, we used an implantable reservoir to administer intra-arterial infusion chemotherapy and reviewed the results. We treated 16 patients with hepatic metastases of colorectal cancer, H2 in 3 cases and H3 in 13 cases. When we used the reduction rate of the tumor diameter as seen by CT scan as a criteria for antitumor effectiveness, 1 case was CR and 3 cases were PR, for an efficacy rate of 25.0%. Changes in the serum CEA level were related to antitumor effectiveness. Among the evaluable cases, the 1-year survival rate was 60.0%, which was significantly more favorable than the 20.0% obtained in the systemic chemotherapy group (p less than 0.05). Given the above, although there are a few problems such as the kind and dose of drugs, the use of intra-arterial infusion chemotherapy with an implantable reservoir to treat hepatic metastases of colorectal cancer permits a form of chemotherapy providing a better QOL out of hospital. PMID- 1908660 TI - [Effects and complications of continuous hepatic arterial infusion chemotherapy using implantable reservoir for liver metastases from colorectal cancer]. AB - Continuous arterial infusion chemotherapy using implantable reservoir was performed for unresectable liver metastases from colorectal cancer and the therapeutic effects, side effects and complications were evaluated. Eleven patients were treated with four kinds of arterial infusion courses that mainly consisted of 5-FU. The arterial infusion courses were discontinued in 2 patients because of nausea and vomiting, and in one patient because of diarrhea. The catheters were dislocated in 2 patients and another 2 developed fistulous between the hepatic artery and bile duct. Three patients developed duodenal ulcer. Serum CEA was reduced in 4 patients (36%). After all, response rate was 9% (1/11). The one-year survival rates of all cases and cases treated with more than 4 courses were 36.3% and 80.0%, respectively. PMID- 1908661 TI - [Experimental study on local attachment of Beriplast P membrane including MMC]. AB - We studied the effect of Beriplast P membrane including MMC (2 mg/ml) on human gastric carcinoma implanted in nude mouse (OSS) as a example of a shallow but broad lesion as with an early-stage local recurrence of rectal cancer and superficial gastric cancer. As a result, the resected tumor contact Beriplast P membrane including MMC after 3 days showed continuous necrotic lesions, from 1 to 2 mm in depth. No side effect was observed in nude mice. These results indicated that Beriplast P membrane including MMC is a useful chemotherapy against local cancerous lesion. PMID- 1908662 TI - [Arterial infusion chemotherapy combined with biochemical modulation in cancer patients]. AB - Both arterial infusion chemotherapy and biochemical modulation are effective for unresectable and recurrent cancer patients. Thus, we tried to combine these methods and studied their combined efficacy in 30 cancer patients. Overall effectiveness was 40% with this method. The efficacy of each regimen, such as beta-MF and CF, was approximately 36.4% and 66.7%, respectively. The effectiveness of cannulation into the proper hepatic artery and aorta was 48.6% and 16.7%, respectively. In this study, there were no serial or severe side effects. These findings suggested that arterial infusion chemotherapy in combination with biochemical modulation was a safe and effective method for treating cancer patients. PMID- 1908663 TI - [The efficacy of intra-arterial infusion chemotherapy in patients with metastatic liver tumors]. AB - The efficacy of intra-arterial infusion chemotherapy for the treatment of liver metastasis was investigated in 28 colorectal cancer patients, 3 gastric cancer patients and 5 breast cancer patients between April 1986 and May 1991. 1. The long-term intra-arterial infusion chemotherapy was a simple and safe method in cancer patients. 2. We examined the serial serum CEA level in cancer patients and found that the serial change in CEA level correlated well with response to chemotherapy. The efficacy of this treatment was approximately 60% in colorectal cancer, 30% in gastric cancer, 80% in breast cancer. Intra-arterial infusion chemotherapy may be an effective treatment for the patients with liver metastasis from colorectal cancers and breast cancers. 3. In 8 colorectal cancer patients, the serum CEA level decrease to half of the pretreatment level. However, in all cases it increased significantly within 6 months postoperatively. Almost the same trend was observed in two cases of breast cancer. Our results suggest that we should give careful consideration to the resistance to anti-cancer drugs and develop a new protocol in order to obtain further satisfactory results. PMID- 1908664 TI - [A study on hepatic arterial infusion for metastatic liver tumor]. AB - This study was designed to evaluate whether hepatic arterial infusion is effective in terms of response rate and survival time of patients with unresectable liver metastasis from colorectal and gastric cancer. In 19 patients with liver metastasis from colorectal cancer, one patient had a CR, 3 had a PR or MR and the remainder showed NC or PD, with an overall response rate of 16.7%. The response rate was higher in men than in women as well as in patients with metachronous liver metastasis. The dose schedules showed no effectiveness in patients with histologically well-differentiated adenocarcinoma. However, there was a statistical difference in survival time according to the response. The overall response rate in 7 patients with liver metastasis from gastric cancer was 42.9% with one patient achieving CR, 2 patients PR and the others PD. As a result, hepatic arterial infusion of antitumor regimen was an effective method for inoperable metastatic liver cancer. PMID- 1908665 TI - [Therapeutic effect of transarterial infusion immunochemotherapy for metastatic liver cancer]. AB - In order to improve therapeutic efficacy for metastatic liver cancer, intermittent transarterial administration of BRM in combination with anticancer drugs was performed by use of reservoir apparatus. A total of 22 patients (12 cases of gastric cancer, 6 of colon cancer, 2 of pancreas cancer, 1 of gall bladder cancer and 1 of biliary tract carcinoid) were treated according to the following schedule: both 10 mg of ADM (or MMC) and 0.5 KE (or 1.0 KE) of OK-432 were administered on day 1 and 40 x 10(4) JRU of recombinant interleukin 2 (r-IL 2) on day 4, 7 and 11. The treatment was repeated as many times as possible. In terms of direct antitumor effect and decrease of tumor marker, the response rate was 43% (6 cases out of 14) and 75% (9 cases out of 12), respectively. As for performance status, improvement, no change and deterioration were seen in 4 cases, 8 cases and 3 cases, respectively. Even though 13 patients died, 8 of them survived more than 300 days. In the case of gastric cancer patients with liver metastasis, 50% survival time of 12 cases was 334 days, while that of 30 cases, who were administered anticancer drugs only systemically, was 144 days. In 3 cases the decrease in the size of tumors located in both liver and the other metastases also was seen. Every case developed high grade fever, but an antifebrile was effective. Otherwise severe side effects were not seen. These results indicated that intermittent arterial infusion immunochemotherapy was feasible for the treatment of metastatic liver cancer. PMID- 1908666 TI - [Long-term arterial infusion chemotherapy combined with external irradiation therapy for unresectable pancreatic cancer--a case report]. AB - A 66-year-old man was referred to our hospital with complaints of intractable abdominal and back pain, and diagnosed to have carcinoma of the pancreatic body. At laparotomy, he was assessed as unresectable because of cancer invasion of the superior mesenteric artery and abdominal aorta. Therefore two catheters connected to an implantable access device were placed in both the gastroduodenal and splenic arteries, in addition to gastrojejunostomy and chemical splanchnicectomy, followed by postoperative external irradiation therapy. The histological examination of the specimen obtained operatively confirmed that the lesion was moderately differentiated adenocarcinoma. Also the nuclear DNA analysis, carried out cytofluorometrically, showed diploid pattern. After discharge from our hospital, the man was treated by intra-arterial infusion chemotherapy in the outpatient department every two weeks. He lived a nearly normal life with satisfactory quality for two years until he died of GI-bleeding. In addition to the fact that the biological aggressiveness of the carcinoma cells assessed by DNA ploidy was relatively low, the combined modality therapy including pain control might benefit patients. PMID- 1908667 TI - [Clinical evaluation of intra-operative pelvic hyperthermochemotherapy combined with operation for rectal cancer]. AB - In order to prevent local recurrence, intra-operative pelvic hyperthermochemotherapy (IOPHC) combined with surgery for rectal cancer has been performed. In this study, we evaluated the clinical effect of IOPHC in 20 patients who were given IOPHC, compared with 13 patients who underwent curative surgery without IOPHC (control group). The IOPHC procedure was as follows: After rectal amputation, the pelvic cavity was filled with a physiological saline containing 40 micrograms/ml of MMC. Then, the physiological saline was warmed and maintained by the apparatus (heater) we devised at 45 degrees C for 90 minutes. Local recurrence occurred in 2 cases of IOPHC group (2/20:10.0%), and in 3 cases in the control group (3/13:23.1%). On the other hand, distant metastases developed approximately at the same rate in the IOPHC group (4/20:20.0%) and control group (2/13:15.4%). Thus, IOPHC is a feasible approach to reduce local recurrence of rectal cancer. PMID- 1908668 TI - [Intraperitoneal administration of cis-platin with arterial infusion chemotherapy of advanced and recurrent gastric cancer]. AB - Arterial infusion therapy was used for 97 patients with AMF therapy. Forty were unresectable, 30 non-curatively resected and 22 recurrent gastric cancers. 5 fluorouracil (5-FU) was administered by arterial continuous infusion, adriamycin (ADM) and mitomycin C (MMC) by bolus infusion in the hospital, and continuous arterial 5-FU infusion and ADM low dose intermittent bolus infusion chemotherapy (AF therapy) was used for outpatients. The clinical effectiveness was evaluated. One year cumulative survival rate of primary case by Kaplan Meier method was 21.6%, and that of recurrent gastric cancer was 4.5%. The median survival periods were 7 months in primary cases and 4 months in recurrent cases. In primary cases, the arterial infusion therapy was more effective in non-curatively resected cases than in unresectable ones. Intraperitoneal administration of cisplatin with AF intraarterial infusion therapy (AF-CDDP therapy) was applied in 11 cases with 9 primary and 2 recurrent cases. The clinical effectiveness of each was evaluated. One-year cumulative survival rate of primary case by Kaplan-Meier method was 28.6% and the median survival periods were 10 months. AF-CDDP therapy was considered more effective for unresectable gastric cancer with carcinomatous peritonitis. In conclusion, our method is considered to be advantageous in the treatment of carcinomatous peritonitis of gastric cancer patients. PMID- 1908669 TI - [CDDP-ip PMUE therapy in gastric cancer cases with liver metastasis]. AB - To reduce liver metastasis and prevent carcinomatous peritonitis, we employed CDDP-ip PMUE therapy in gastric cancer cases with liver metastasis exceeding P0H2S2. Therapy consisted of cis-diammine-dichloroplatinum-ip (CDDP-ip), mitomycin C (MMC), uracil and futraful (UFT) and etoposide. From January 1990 to March 1991, primary lesions were resected in 6 gastric cancer cases with liver metastasis exceeding H2. On the basis of therapy, subjects were classified into 2 groups and the therapeutic effects were compared between them. One group was composed of 3 patients who were placed on CDDP-ip PMUE therapy beginning the 14th day after gastrectomy. The other group was composed of 3 patients who received only UFT oral administration (300 mg/body). As a rule, the following was the CDDP ip PMUE therapy schedule: CDDP intraperitoneal administration (75 mg/m2) and MMC intravenous injection (10 mg/body) on day 1; etoposide intravenous injection (30 mg/body) on days 2 to 6; and consecutive UFT oral administration (300 mg/body). One case showed MR in a metastatic liver lesion, but treatment proved ineffective in the other cases. Although the 2 patients in the CDDP-ip PMUE therapy group, surviving 315 and 216 days, respectively, died of primary disease and hepatic insufficiency due to an increase in metastatic liver lesions, the third patient has been in good condition for 175 days. This therapy was thought to have prolonged survival. The post-operative survival period in the group of patients receiving only UFT oral administration ranged from 36 to 243 days, with all patients dying of primary disease. The main adverse effects of this therapy (i.e., digestive symptoms, leukopenia, and thrombocytopenia) were slight and transient in all cases. Because the subjects studied were gastric cancer cases exceeding H2, the present investigation resulted in the increase of metastatic liver lesions, a problem to be studied in future. PMID- 1908670 TI - A scanning electron microscope study of microcorrosion casts of the microvasculature of the marmoset palate, gingiva and periodontal ligament. AB - In the hard palate, sagittally oriented capillary loops, 8-10 microns in diameter and 70-250 microns high, extended perpendicularly from a subcapillary plexus to the connective tissue papillae. These loops formed a well-delineated vascular spine beneath the rugal crests. Capillary loop density was estimated to be 200 270/mm2 on the rugal crest, 75-160/mm2 on the rugal slopes and 70-140/mm2 in the trough. In the gingiva, the crevicular loop system was separated by a gap from the vestibular, palatal and col loop systems. Anastomoses occurred between these systems at a deeper level. The crevicular circular plexus varied from 1 to 4 vessels. Apical to the gingival margin the buccal vasculature was composed of occluso-apically orientated loops draining towards the vestibular sulcus. The capillary loops were 60-120 microns high near the gingival margin, compared with 40-60 microns near the mucogingival junction. The mucogingival margin was demarcated by a change in capillary orientation. The periodontal ligament contained mainly postcapillary-sized venules, 10-25 microns in diameter, orientated occluso-apically. Capillary loops, 50-100 microns long and directed at right angles to the root surface, occurred in the cervical third. These microvascular patterns of the marmoset are different from those of the mouse and rat. PMID- 1908671 TI - The pH of gingival crevices and periodontal pockets in children, teenagers and adults. AB - Gingival crevice and periodontal pocket pH, measured directly with glass micro electrodes, was near neutral at most sites in most individuals (mean pH 6.92 +/- 0.03 SEM, 69 subjects). Periodontal state ranged from healthy to periodontitis but neither clinical evidence of gingivitis at a site nor pocket depth were associated with crevicular pH different from that at healthy sites. This finding contradicts earlier reports that gingivitis is associated with a crevicular pH as alkaline as pH 9.06. Metallic antimony electrodes as used by earlier investigators were found to give pH readings that were too high by as much as 1.5 pH units in the presence of organic reducing agents of the type produced by oral bacteria within gingival crevices. In contrast, glass micro-electrodes respond only to hydrogen ions and thereby provided accurate measurements of pH even in the presence of organic reducing agents. Loss of CO2 to the atmosphere from biological fluids that are bicarbonate buffered resulted in a shift to alkaline pH by as much as 1 pH unit. As a result, only measurements taken within gingival crevices or periodontal pockets can provide accurate measurements of crevice or pocket pH. PMID- 1908672 TI - Plasminogen activator in human periodontal health and disease. AB - Plasminogen activators, proteases associated with the fibrinolytic system, also play a major part in extravascular processes such as tissue remodelling, cell migration and activation of prohormones, growth factors and other proteases. It is likely that plasminogen activators participate in the pathophysiology of periodontal disease. Plasminogen activator has been identified in human gingival crevicular fluid in a concentration 100-fold greater than in plasma. The local activity of plasminogen activator in gingival tissues was examined and changes detected in its distribution in relation to the extent of disease. Frozen sections from human gingival biopsies were overlaid on fibrin-coated slides; tissue-type plasminogen activator activity was found in all samples. Focal activity was observed in healthy tissue, originating from the most superficial cells of the junctional epithelium. Biopsies of clinically healthy sites obtained 6 weeks after treatment for periodontitis also showed epithelial plasminogen activator activity localized to this area. In contrast, in diseased tissue the entire epithelium lining the periodontal pocket showed activity. This differential pattern of activity in health and disease is consistent with the hypothesis that plasminogen activator is a modulator of periodontal homeostasis. PMID- 1908673 TI - Muromonab-CD3. PMID- 1908675 TI - Lipoxygenases from soybeans and rabbit reticulocytes: inactivation and iron release. AB - Various inactivation methods were applied to lipoxygenases from soybean (isoenzyme 1) and rabbit reticulocytes to compare the inactivation behaviour of both enzymes and to elucidate the state of the iron which is known to be involved in the catalytic reaction of lipoxygenases: 1. Titration of the enzyme with mercury compounds shows that there are one or two SH groups responsible for the loss of activity in the presence of mercury. The SH groups seem not to be involved in the tight iron binding. 2. Inactivation by chelating agents such as o phenanthroline or batho-phenanthroline sulfonic acid occurs only in the presence of reducing agents (mercaptoethanol and ascorbic acid). Our data support a co oxidation mechanism. The complexation of iron by chelators is not the rate limiting step. Both lipoxygenases show a very similar behaviour in this respect despite the fact that the reticulocyte enzyme requires the addition of trace amounts of copper ions for efficient inactivation. 3. Release of iron from the enzyme is also achieved by denaturation with guanidinium hydrochloride (Gu-HCl). In all cases, inactivation and release of iron were irreversible processes. 4. A sequence comparison for both animal and plant lipoxygenases shows strongly conserved amino acids, especially histidines and hydrophobic residues, which possibly may be involved in iron complexation and substrate binding. PMID- 1908676 TI - [Comparison between alpha-amylase from B. amyloliquefaciens and B. licheniformis]. AB - Two sequence-homologous alpha-amylases from B. amyloliquefaciens and B. licheniformis were studied with respect to their stability against heat denaturation and were compared with respect to common structure-stabilizing principles. The investigated alpha-amylases were isolated from culture broth of B. amyloliquefaciens and B. licheniformis. The molecular parameters (molecular weight and isoelectric point) are similar. The thermostability was determined by changes of the protein structure (changes of the fluorescence emission spectra). At pH 5.0 the thermostable alpha-amylase from B. licheniformis showed a rate of denaturation which was achieved by the thermolabile alpha-amylase from B. amyloliquefaciens at a temperature 15 degrees lower. The alpha-amylase from B. licheniformis exhibits a marked stability also at the alkaline pH-range in contrast to the alpha-amylase from B. amyloliquefaciens. From measurements in the presence of EDTA and Ca2+ follows that both enzymes are stabilized by binding of calcium ions. An analysis of preferred amino acid exchanges between the two sequence-homologous alpha-amylases showed correspondences and differences to the well-known diagram of ARGOS. Possibly an increased thermic stability can already be achieved by special amino acid exchanges without significant changes in the protein structure. PMID- 1908677 TI - Drug-acetaldehyde interactions during ethanol metabolism in vitro. AB - Acetaldehyde, at concentrations occurring in vivo was found to avidly react in vitro with several clinically relevant drugs. The greatest reactivity was observed for the hydrazine and hydrazide-containing drugs, hydralazine and isoniazid, respectively. Substantial reactivity was also evidenced for the amine containing penicillins cyclacillin and ampicillin and for the cephalosporins cephalexin, cephradroxyl and cephradine. However, the virtual lack of reactivity of the amine-containing penicillanic and cephalosporanic acids reveals a major role of the acyl groups of these antibiotics in their reactivity towards acetaldehyde. The presence of moieties which increase the electron density of the amine group appears to favour the molecule reactivity. Amongst several phenylethylamines tested, dopamine and noradrenaline were the most active in forming adducts with acetaldehyde. It is suggested that in vitro binding of acetaldehyde to the above-mentioned drugs could lead in vivo to decreased drug bioavailability, and conceivably the adducts formed may mediate some of the side effects associated with simultaneous drug and alcohol ingestion. PMID- 1908674 TI - Adrenergic agents, but not triiodo-L-thyronine induce c-fos and c-myc expression in the rat heart. AB - We have examined the expression of two nuclear-acting oncogenes, c-fos and c-myc in the rat heart following administration of hormones implicated in the development of cardiac hypertrophy. A single injection of norepinephrine (2.5 micrograms/kg to 2.5 mg/kg) led to transient increases in the levels of both c fos and c-myc mRNA. The response was sequential: elevated levels of c-fos mRNA were first observed 15 min after treatment and peaked at 1 h whilst c-myc mRNA levels increased 30 min after treatment and peaked at 2 h. The response of both cellular oncogenes to norepinephrine was reduced significantly by alpha blockade but beta blockade was less effective. Administration of triiodo-L-thyronine (0.25 mg/kg), a level known to promote cardiac hypertrophy, did not produce elevated levels of c-fos or c-myc mRNA. In an initial study, it was possible to demonstrate induction of c-fos and c-myc in rat hearts perfused in vitro with medium containing 2 x 10(-7) M norepinephrine. These results provide support for the notion that c-fos and c-myc expression may play a transducing role in the development of adrenergic-mediated, but not thyroid hormone-mediated cardiac hypertrophy. PMID- 1908678 TI - [Intestinal microsporidiosis. 3 cases in HIV seropositive patients]. AB - Three cases of intestinal microsporidiosis are reported, in acquired immunodeficiency syndrome patients, with a chronic diarrhea. The first case is associated with an intestinal cryptococcosis and with a cytomegalovirus infection and the second case was diagnosed on ileal biopsy specimen. Since the first description of Enterocytozoon bieneusi in 1985. 49 cases of intestinal microsporidiosis are reported in the literature, all in AIDS patients and the frequency of this infection is probably underrated. Prospective studies find it in 6 to 30% of cases. This parasite must be suspected in HIV seropositive patients with clinically chronic unexplained diarrhea or with intestinal atrophy. PMID- 1908680 TI - Rhabdomyolysis in children: a 3-year retrospective study. AB - The case reports of 4 pediatric patients illustrate the complex clinical scenarios in which childhood rhabdomyolysis/myoglobinuria occurs. Children ranged in age from 8-18 years. Presumed etiologies of rhabdomyolysis/myoglobinuria included Neisseria sepsis, exertion-related episodes, dialysis disequilibrium, and diabetic ketoacidosis. No child developed respiratory or renal failure. all children were discharged with normal muscle power, indicating the benign nature of this disease and the importance of aggressive management. PMID- 1908679 TI - Carnitine deficiency associated with ornithine transcarbamylase deficiency. AB - An infant with X-linked recessive ornithine transcarbamylase deficiency is described who also had severe deficiency of plasma and liver carnitine during normoammonemic periods. Treatment with L-carnitine (100 mg/kg/day) for 12 months decreased the frequency of hospitalizations for hyperammonemia, although it did not alter his neurologic status. This report demonstrates that persistent carnitine deficiency may be present in patients with ornithine transcarbamylase deficiency even when plasma ammonia is normal. Carnitine evaluation and supplementation may be important in the treatment of patients with this metabolic disorder. PMID- 1908681 TI - Pressure reduction mattresses. Guidelines for evaluating clinical use and cost effectiveness. PMID- 1908682 TI - Plasma thyrotropin concentration in the male pig: profile from birth to puberty and the effect of season and social environment in the young adult. AB - Plasma thyrotropin (TSH) secretion was studied in crossbred (Landrace x Large White) immature and young adult Landrace male pigs. Levels of TSH were low over the first 9 wk post-natally and were maximal at 12 wk of age. Thereafter, hormone levels declined and by 16 wk returned to values similar to those at 7 wk. In addition, a transient increase in TSH was noted at 22 wk. A second experiment involved 2 groups of young adult boars housed either in a socially non restrictive environment (adjacent to estrual females) or a socially restrictive environment (not in direct physical contact with females). TRH stimulated secretion of TSH and the magnitude of this response was affected by month; minimum and maximum responses were found in May and August respectively. There was an effect of social environment on TRH-induced TSH secretion; during February and August, the magnitude of the TSH response to TRH was lower in socially restricted than in socially non-restricted boars. PMID- 1908683 TI - Frontal lobe seizures: no evidence of self-injury. PMID- 1908684 TI - Cytochalasin D treatment induces meiotic resumption in follicular sheep oocytes. AB - Ovine cumulus-enclosed oocytes collected from antral follicles (3-5 mm in diameter) were cultured in vitro with 2 x 10(6) granulosa cells/ml in the presence or absence of gonadotropins or in the presence of cytochalasin D (CD). The maturation rate was assessed after 24 h of culture. In the control group, in the presence of gonadotropins (follicle-stimulating hormone-luteinizing hormone (FSH-LH; -10 micrograms/ml) 100% of the oocytes reached metaphase II. Whereas intercellular junctions were no longer present after 6-7 h of culture, germinal vesicle breakdown (GVBD) occurred by the same time. In contrast, in the absence of gonadotropin, the majority of the oocytes (59%) remained blocked in GV stage. The inhibition exerted by the granulosa cells on meiotic resumption was overcome when the cumulus-oocyte complexes (COCs) were incubated in CD (5 micrograms/ml) for 6 h at the beginning of the culture. Under these conditions, 85% of the oocytes matured with extrusion of the first polar body. Cytological analysis by cytofluorescence (NBD phallacidin) and electron microscopy showed that, after 6 h of treatment, CD provoked a redistribution of the microfilaments, mainly in the cumulus cells and to a lesser extent in the oocyte cortex. Intercellular junctions disappeared concomitantly with a significant decrease of the intercellular transport of tritiated uridine. The initiation of GVBD occurred at the same time. These results indicate that the resumption of meiosis was correlated with a loss of both junctional complexes (intermediate and gap junctions) between the cumulus cells and the oocyte. PMID- 1908685 TI - Guinea pig proacrosin is synthesized principally by round spermatids and contains O-linked as well as N-linked oligosaccharide side chains. AB - Proacrosin is the zymogen precursor of acrosin, a sperm protease believed to play an essential role in fertilization. In this study, we used primary cultures of guinea pig spermatogenic cells to examine the temporal appearance and mechanisms of synthesis and processing of proacrosin during acrosome development. Following [35S]methionine incorporation and immunoprecipitation, cultured spermatogenic cells were found to synthesize two forms of proacrosin (Mr 54,000 and 57,000). Proacrosin was synthesized mainly by round spermatids. By immunoblotting, proacrosin became very prominent in round spermatids and persisted throughout spermiogenesis. Pulse-chase experiments demonstrated that the Mr 54,000 form of proacrosin was converted to the Mr 57,000 form, presumably reflecting posttranslational processing of carbohydrate side chains. When spermatogenic cells were cultured in the presence of tunicamycin, the synthesized proacrosin had an Mr of 54,000. However, in vitro translation of mRNA extracted from guinea pig testis followed by immunoprecipitation indicated that the core polypeptide of proacrosin has an Mr of 44,000. Guinea pig spermatogenic cells incorporated glucosamine and fucose into the oligosaccharides of proacrosin. Treatment of guinea pig testis proacrosin with N-glycosidase or O-glycosidase reduced the Mr by 3-7%. These results indicate that proacrosin is synthesized by postmeiotic cells and the enzyme contains N- and O-linked oligosaccharides. PMID- 1908686 TI - Interferon-gamma activates rat alveolar macrophages for anticryptococcal activity. AB - Cryptococcus neoformans is a pathogenic yeast causing disease predominantly in immunosuppressed patients. C. neoformans is acquired by the pulmonary route, where the alveolar macrophage (AM) is a resident mechanism of host defense. The ability of rat AM to be activated by products of the immune response for enhanced anticryptococcal effect has not previously been demonstrated. Rat AM could be activated in vitro for anticryptococcal activity by medium conditioned by concanavalin A-stimulated splenic lymphocytes. A monoclonal antibody that neutralizes interferon-gamma (IFN-gamma) inhibited the macrophage-activating activity of lymphokine-containing medium (LCM). Further, recombinant IFN-gamma activated AM for anticryptococcal activity. The concentration of IFN-gamma in LCM, determined by enzyme-linked immunosorbent assay, was equivalent to the range of concentrations of recombinant IFN-gamma which activated AM. Thus, IFN-gamma was necessary and sufficient for optimal macrophage activation by medium conditioned by proliferating lymphocytes. Lipopolysaccharide could not enhance the anticryptococcal activity produced by optimal concentrations of LCM or IFN gamma but did augment the effects of submaximal stimulation. Both LCM and recombinant IFN-gamma increased the percentage of macrophages with cell associated cryptococcus, suggesting that activation of AM enhanced the adhesion or uptake of cryptococcus. We speculate that inadequate availability of lymphokines such as IFN-gamma may result in the immunodeficient state in hosts unable to generate an appropriate response to cryptococcal antigens. Administration of lymphokines such as IFN-gamma to immunosuppressed hosts might circumvent the defect in cell-mediated immunity. PMID- 1908687 TI - Reduced activity of acetylcholinesterase in canine tracheal smooth muscle homogenates after active immune-sensitization. AB - Previous investigations have suggested that immune-sensitization increases airway smooth muscle responsiveness to cholinomimetic stimulation by reducing the rate of degradation of acetylcholine. To examine the hypothesis that increased cholinomimetic responsiveness of tracheal smooth muscle (TSM) caused by immune sensitization results from inhibition of acetylcholinesterase (AChase) activity, we developed a method for direct measurement of AChase activity in homogenates of TSM obtained from mongrel dogs actively sensitized in vivo to ragweed pollen extract (n = 7) and sham-sensitized littermate controls (n = 7). For both sensitized and control specimens, saturation of AChase was obtained at approximately 3.12 mM substrate (acetylthiocholine); however, maximal enzyme activity in homogenates of ragweed-sensitized tissues was significantly less (0.862 +/- 0.088 absorbance units/min/mg protein [AU/min/mg]) compared to control homogenates (1.590 +/- 0.129 AU/min/mg; P less than 0.001). Kinetic analysis (Eadie-Hofstee plot) indicated similar Michaelis constants (Km) for AChase from ragweed-sensitized (0.360 +/- 0.063) and control (0.336 +/- 0.062) homogenates (P = NS). The concentration of physostigmine eliciting half-maximal inhibition (Ki) of AChase activity also was similar for tissues from sensitized (-7.92 +/- 0.032 log M) and control animals (-7.86 +/- 0.012 log M; P = NS). Pretreatment with selected mediators of anaphylaxis (10(-4) M histamine, 10(-6) M serotonin, 10(-5) M prostaglandin E2, 10(-6) M prostaglandin F2 alpha, and 10(-7) M leukotriene D4) did not affect AChase activity. Our data demonstrate reduced AChase activity in homogenates of canine TSM after active immune-sensitization in vivo. This corresponds to functional augmentation of cholinomimetic contraction in actively sensitized tissues. PMID- 1908688 TI - Purification and level of expression in bronchoalveolar lavage of a human polychlorinated biphenyl (PCB)-binding protein: evidence for a structural and functional kinship to the multihormonally regulated protein uteroglobin. AB - A human lung polychlorinated biphenyl (PCB)-binding protein was purified by sequential chromatography of lavage fluid incubated with the tritium-labeled, high-affinity ligand, 4,4'-bis(methylsulfonyl)-2,2',5,5'-tetrachlorobiphenyl. From sodium dodecyl sulfate polyacrylamide gel electrophoresis gradient gels, it was evident that a single band with an approximate molecular weight of 13 kD was present in the eluate from the final chromatographic step. Antibodies raised against the human lung PCB-binding protein detected a single band of corresponding size in lavage fluid in immunoblotting experiments. Furthermore, the antibodies detected significantly higher levels of the lung PCB-binding protein in lavage fluid from nonsmokers as compared to smokers. The purified protein was sequenced, and an alignment of the obtained aminoterminal amino acid residues of the human lung PCB-binding protein to uteroglobin and to a rat lung PCB-binding protein revealed an overall positional identity of approximately 45%. The amino acids suggested to participate in ligand binding of uteroglobin were extensively conserved in the PCB-binding proteins. Thus, we conclude that we have purified and raised antibodies against a human lung PCB-binding protein and that it has a structural as well as a functional kinship to the steroid-binding and multihormonally regulated rabbit protein uteroglobin. PMID- 1908689 TI - Signal transduction in human alveolar macrophages: diminished chemotactic response to FMLP correlates with a diminished density of Gi proteins and FMLP receptors. AB - Alveolar macrophages (AM) migrate less well in response to chemotactic ligands than do monocytes and neutrophils. The response of monocytes and neutrophils to chemotactic ligands is mediated at least in part by pertussis toxin-sensitive guanine nucleotide binding proteins (Gi proteins). Whether this is also true in AM is uncertain. We hypothesized that decreased chemotaxis by AM was due in part to diminished Gi protein and/or chemotactic receptor density in AM. G proteins are heterotrimers made up of alpha, beta, and gamma subunits; the predominant pertussis toxin-sensitive Gi proteins are those containing alpha i2 or alpha i3 subunits. Pertussis toxin pretreatment (0.5 microgram/ml) significantly reduced AM, monocyte, and neutrophil chemotaxis to N-formyl-L-methionyl-L-leucyl-L phenylalanine (FMLP) and human zymosan-activated serum (P less than 0.05). However, as previously noted, AM chemotaxis was much less than that observed in monocytes and neutrophils. Immunoblots using antibodies that are specific for alpha i2 and alpha i3 showed that AM contained approximately 3-fold less alpha i2 and approximately 10-fold less alpha i3 per microgram of plasma membrane protein than did monocytes or neutrophils. Similar results were obtained in immunoblots made using antibodies to common alpha subunit determinants and to the beta 36 subunit. A comparable approximately 4-fold reduction in density of receptors for [3H]FMLP was found in AM compared to neutrophils. The diminished density of Gi proteins and FMLP receptors was not due to a generally decreased density of plasma membrane proteins in AM, since the density of the membrane-associated tyrosine kinase hck was similar in AM, monocytes, and neutrophils.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1908690 TI - Analysis of circulating immune complexes (CIC) in tuberculosis: levels of specific antibody and antigens in CIC and relationship with serum antibody. AB - Eighty sera from tuberculosis (TB) patients, 16 Indian and 10 American control sera were analyzed by ELISA for relative titres of antibody against mycobacterial antigens. Levels of specific antibody and mycobacterial Ag in circulating immune complexes (CIC) isolated from these sera were also studied. All these parameters were found to be elevated in TB sera as compared to control sera. Maximum increase was however noted in CIC specific antibody titres. A good correlation was observed between serum and CIC levels of specific antibody (r = 0.72) and between specific antigen (Ag) and antibody (Ab) levels within CIC (r = 0.64). In a few of the TB sera examined, CIC specific Ab contributed less than 1% to the Ab titres in sera. In order to examine the differences between different subgroups within TB patients, a statistical analysis of variance was performed. Sex of the patients had no effect on any parameter. Sputum-positive patients had significantly higher levels of CIC Ag and Ab than the sputum-negative patients, although no significant difference occurred in respect to serum Ab. All three parameters were significantly higher in patients on chemotherapy as compared to fresh untreated cases. The relevance of these observations to the development of a CIC-based immunodiagnostic assay for TB is discussed. PMID- 1908691 TI - Phagocytosis of enteric Campylobacter by human and murine granulocytes. AB - The phagocytosis of enteric Campylobacter strains by murine and human granulocytes was studied in vitro. The number of fluorescein isothiocyanate labelled bacteria per granulocyte was determined microscopically. The phagocytic index is strain-dependent, ranging from 0.05 to 0.4 bacteria per granulocyte. Human granulocytes phagocytose Campylobacter sp. with a twofold higher effectivity than murine cells. Opsonization with immune sera increased phagocytosis 11.6-fold; flagella-defective mutants were phagocytosed without opsonization with 3.3-fold higher effectivity than the isogenic mother strain. Stimulation and phagocytosis of granulocytes by 14 clinical isolates of Campylobacter sp. was monitored by measuring the oxidative burst and phagocytosis. Stimulation of granulocytes varied from 0.4 to 1.8 (relative units) and phagocytosis ranged from 0.03 to 0.68 bacteria per granulocyte. No statistically significant correlation among bio- or serovars and the degree of stimulation and phagocytosis was observed. PMID- 1908692 TI - In Lactococcus lactis subsp. cremoris SK110 protein, instead of lipoteichoic acid, reacts with the group-N-specific antiserum. AB - The reaction between cell-surface components, isolated from two Lactococcus lactis subsp. cremoris strains, with their Group-specific antiserum were studied. No reaction between purified lipoteichoic acid and the antiserum was observed. Both strains, however, did belong to the lactococci (Group-N streptococci), as was demonstrated by the positive reaction between the antiserum and an acid- (Lancefield) or alkaline-extract. Experiments with proteolytic enzymes demonstrated the involvement of protein in the antigenic material in the latter reaction. PMID- 1908693 TI - Characterization of a soluble ferric reductase from Neisseria gonorrhoeae. AB - An NADH-dependent ferric reductase was identified in extracts of Neisseria gonorrhoeae. Enzyme activity was measured in an assay using ferrozine as the ferrous iron acceptor. Ferric reductase activity was enhanced by Mg2+ and flavine nucleotides. The enzyme reduced both citrate- and diphosphate-bound ferric iron as well as ferric hydroxide (Imferon). However, no activity was observed with either 30%-iron-saturated transferrin or with the gonococcal iron-binding protein, Fbp. The ferric reductase was found primarily within the cytoplasmic cell fraction. The soluble ferric reductase was purified 110-fold by ammonium sulfate precipitation, gel and anion-exchange chromatography. Results obtained following gel chromatography and SDS/polyacrylamide gel electrophoresis suggested that the enzyme had a molecular mass of about 25 kDa. PMID- 1908694 TI - Inhibition of phosphatidic acid production and lysophospholipid formation in collagen-stimulated human platelets by staurosporine, a protein kinase inhibitor. AB - To investigate a possible regulatory role of protein kinase C (PKC) on collagen induced phospholipase activity, human platelets were prelabelled with either [3H] arachidonic acid or [14C]stearic acid and stimulated with collagen (2 micrograms/ml) in the presence or absence of the protein kinase inhibitor, staurosporine (1 microM). The collagen-induced release of [3H]arachidonic acid and formation of [14C]stearoyl-labelled lysophospholipids was inhibited by prior incubation with staurosporine, as was the formation of 3H-labelled thromboxane B2, thereby suggesting inhibition of the collagen-induced phospholipase A2 activity. The degradation of phosphatidylinositol (PI) and elevation of phosphatidic acid (PA) in platelets prelabelled with either radiotracer were also completely blocked by staurosporine pretreatment, indicating a suppression of collagen-stimulated phospholipase C activity. Suppressed phospholipase C activity may have been due to diminished thromboxane A2 formation since treatment with the dual cyclo-oxygenase/lipoxygenase inhibitor, BW755C, also resulted in an inhibition of the collagen-stimulated loss of 14C-labelled PI and rise in PA by 75-80%. Our results suggest that protein kinase, possible PKC, may be involved in the regulation of these phospholipases in collagen-stimulated human platelets. PMID- 1908696 TI - Toxic marine and freshwater algae: an occupational hazard? PMID- 1908695 TI - Role of Ca2+ in t-PA production by human embryonic lung diploid fibroblast, IMR 90 cells, stimulated by proteose peptone. AB - Proteose peptone (p.peptone) remarkably induced tissue plasminogen activator (t PA) activity in the conditioned medium of confluently cultured human embryonic lung diploid fibroblast, IMR-90 cells, in a dose-dependent manner. t-PA activity correlated well with the amount of t-PA antigen found in the conditioned medium of IMR-90 cells stimulated by p.peptone. t-PA production by IMR-90 cells stimulated by p.peptone was dependent on extracellular Ca2+ concentration and maximum t-PA production required approximately 3.6 mM extracellular Ca2+. Conversely, elimination of Ca2+ from the culture medium by EGTA, Ca2+ chelate agent, strongly inhibited t-PA production induced by p.peptone. t-PA production induced by p.peptone was inhibited in a dose-dependent manner by Verapamil, which inhibits Ca2+ uptake through the slow channels and also by W-7, an inhibitor of calmodulin. These results suggested that influx of extracellular Ca2+ into IMR-90 cells was caused by p.peptone and induced t-PA production by the cells. PMID- 1908697 TI - Effect of person. 1966. PMID- 1908698 TI - A novel autoantibody reactive with carbonic anhydrase in sera from patients with systemic lupus erythematosus and Sjogren's syndrome. AB - Carbonic anhydrase (CA) is an extremely basic zinc metalloenzyme with a wide phyletic distribution, and the enzyme is important for the regulation of acid base status. A novel autoantibody reactive with carbonic anhydrase was demonstrated. Several different classes of CA are known in mammals. Using the immuno blotting method and and immun-dot analysis, we found this autoantibody to be reactive with CA in the sera from patients with Sjogren's syndrome (20.8%), including a patient with Sjogren's syndrome and renal tubular acidosis, and in patients with systemic lupus erythematosus (31.6%). The autoantibody varied in the extent of its cross-reactivity among human CA I (or B), human CA II (or C), bovine CA I, bovine CA II, rabbit CA, and dog CA. The titers continued to float and tended to parallel disease activity. Positive reactivity of autoantibody was observed on eccrine sweat glands and the distal tubules of the kidney by the indirect immunofluorescent method. PMID- 1908700 TI - Orientation of carotenoids in the outer membrane of Synechocystis PCC 6714 (cyanobacteria). AB - The orientation of outer membrane carotenoids from Synechocystis PCC 6714 and Synechococcus PCC 6307 was studied by linear dichroism spectrophotometry. Uniaxially oriented, tilted outer membrane films revealed a significant linear dichroism after rotating the polarization vector of the incident light beam, indicating a predominant orientation of the carotenoid transition moments perpendicular to the outer membrane plane. Values for the reduced dichroism at the absorbance maxima presented a linear correlation to a function of the tilt angle (sin2 alpha). PMID- 1908699 TI - Utilization of ileal digestible amino acids by growing pigs: threonine. AB - An experiment was conducted to determine the utilization of ileal digestible threonine by growing pigs. Three threonine-deficient diets (0.22 g ileal digestible threonine/MJ digestible energy (DE] were formulated using cottonseed meal, meat-and-bone meal and soya-bean meal respectively, as the only source of threonine in the diet. An additional three diets were formulated with supplements of threonine to confirm that threonine was limiting in the first three diets. The growth performance and retention of threonine by pigs given the six diets over the 20-45 kg growth phase was then determined. Growth rates (g/d) of the pigs given the three diets formulated to 0.22 g ileal digestible threonine/MJ DE were significantly different (P less than 0.001): cottonseed meal 417, meat-and-bone meal 452, soya-bean meal 524 (SED 13.6). The response of pigs to the addition of threonine confirmed that threonine was limiting in these diets. Crude protein (nitrogen x 6.25) deposited by the pigs (g/d) was significantly higher (P less than 0.001) for those given soya-bean meal (75), relative to meat-and-bone meal (62) and cottonseed meal (47) (SED 3.3). The proportion of ileal digestible threonine retained by pigs given the three protein concentrates was: cottonseed meal 0.44, meat-and-bone meal 0.59, soya-bean meal 0.64 (SED 0.024). These results indicate that values for the ileal digestibility of threonine in protein concentrates are unsuitable in dietary formulations as the assay does not reflect the proportion of threonine that can be utilized by the pig. It appears that, with heat-processed meals, a considerable proportion of the threonine is absorbed in a form(s) that is (are) inefficiently utilized. PMID- 1908701 TI - Dilution of activated glutaraldehyde solution in an automatic endoscope washer. PMID- 1908702 TI - Intron A (interferon-alpha-2b recombinant) for injection/Schering-Plough Corporation. AB - Intron A (Interferon-alpha-2b Recombinant) for injection, a product by Schering Plough Corporation, is a recombinant DNA, genetically engineered copy of a naturally occurring protein which acts as an antiviral agent. This product is now approved in the United States for the treatment of chronic non-A, non-B hepatitis, also known as hepatitis C. Intron A represents an important advance in the treatment of chronic hepatitis non-A, non-B/C because until now, although many other drugs have been tried, there has been no effective treatment. PMID- 1908703 TI - Glutaraldehyde use in endoscopy: a Canadian review. AB - Endoscopy units in 27 large teaching hospitals in Canada were surveyed to ascertain which solution was being used to soak endoscopic equipment. The purpose of this survey was to discover if staff in endoscopy units were experiencing side effects as a result of exposure to the soaking solutions. The type of solution used, the use of washing machines and the addition of ventilation are examined in relation to the side effects experienced. The results of the survey showed that five solutions were being used by GI units to soak and clean scopes. All five of the solutions contained some glutaraldehyde, and side effects were reported by staff using all five solutions. The use of washing machines and additional ventilation at some of the hospitals may have had an effect on the number of side effects experienced, but the results could not be used to determine their effect conclusively. PMID- 1908704 TI - Carboxymethyl-substituted bifunctional chelators: preparation of aryl isothiocyanate derivatives of 3-(carboxymethyl)-3-azapentanedioic acid, 3,12 bis(carboxymethyl)-6,9-dioxa-3,12-diazatetradecanedioic++ + acid, and 1,4,7,10 tetraazacyclododecane-N,N',N",N'''-tetraacetic acid for use as protein labels. AB - 3-(Carboxymethyl)-3-azapentanedioic acid (NTA), 3,12-bis(carboxymethyl)-6,9-dioxa 3,12-diazatetradecanedioic acid (EGTA), and 1,4,7,10-tetraazacyclododecane N,N',N",N'''-tetraacetic acid (DOTA) structures having a 4-nitrophenyl substituent attached via an alkyl spacer to the methylene carbon atom of one carboxymethyl arm of the chelator were obtained by alkylation of 4 nitrophenylalanine with bromoacetic acid (NTA), by reductive alkylation of 1,8 diamino-3,6-dioxaoctane with (4-nitrophenyl)-pyruvic acid followed by alkylation with bromoacetic acid (EGTA), and by alkylation of the trimethyl ester of 1,4,7,10-tetraazacyclododecane-N,N',N"-triacetic acid with the methyl ester of alpha-bromo-4-(4-nitrophenyl)pentanoic acid and subsequent saponification (DOTA). The nitrophenyl-substituted chelators were converted to the corresponding amines by hydrogenation then reacted with thiophosgene to give the protein-reactive aryl isothiocyanate derivatives. PMID- 1908705 TI - Diazo- and azido-functionalized glutaraldehydes as cross-linking reagents and potential fixatives for electron microscopy. AB - The synthesis of diazo and perfluorophenyl azide (PFPA) functionalized glutaraldehydes 7 and 13a-d as new cross-linking reagents for bioconjugation and potential fixatives for electron microscopy is reported. A key step is the generation of the 1,5-dialdehyde structures by oxidative cleavage of the corresponding cyclopentene epoxide using HIO4 in aqueous tetrahydrofuran. A model reaction between 3-substituted glutaraldehyde 14 and 6-aminohexanoic acid resulted in the formation of pyridinium ion containing products with UV spectra comparable to those observed with glutaraldehyde itself. Thus modification of glutaraldehyde in the 3-position most probably did not significantly change its reactivity with amines under chemical-fixation conditions. Fixation of red blood cells by 7 demonstrates that as a fixative, 7 is comparable to glutaraldehyde. PMID- 1908706 TI - Characterization of antibody-chelator conjugates: determination of chelator content by terbium fluorescence titration. AB - Fluorescence titrations were performed by adding varying mole ratios of terbium(III) to antibody conjugates formed by benzyl isothiocyanate derivatives of three different polyaminopolycarboxylate chelators (NTA, EDTA, and DTPA) and the results compared to values for average chelator content obtained by cobalt-57 binding assays. For two different murine monoclonal antibodies, the average chelator content obtained by terbium fluorescence titration correlated closely with that measured by the cobalt-57 binding assay. It is concluded that lanthanide fluorescence titrations provide a useful alternative to radiometal binding assays for the determination of chelator content in protein-chelator conjugates. PMID- 1908707 TI - Monoclonal antibodies EBU-141 (CDw75) and EBU-65 allow reliable distinction between mature and pre-B-cell tumors in suspension and on tissue sections. AB - Two new monoclonal antibodies, EBU-65 and EBU-141, were raised by immunization with plasma cell line U-266. Both antibodies strongly react with B lymphocytes in immunofluorescent staining as well as on paraffin-embedded sections. More than 200 leukemias and lymphomas were tested, and for both antibodies reactivity was found only with "mature" B-cell tumors but not with precursor B-cell leukemias. None of the non-B-lineage hematolymphatic tumors tested was stained by EBU-141 or EBU-65. A subpopulation of T lymphocytes particularly present in nonmalignant pleural effusions was detected by EBU-65 additionally. Although EBU-141 was clustered as CDw75 and EBU-65 as "unique," a close relationship of the staining pattern was found and both antibodies react with a sialyltransferase. In particular, CDw75 antibody EBU-141 was demonstrated to be very useful for immunophenotyping of B-cell neoplasias, while EBU-65 reacted with most multiple myelomas and a subgroup of "activated"-appearing T cells. PMID- 1908708 TI - Serum erythropoietic inhibitors in patients with pure red cell aplasia. AB - Inhibitory mechanisms of erythropoiesis in 20 patients with pure red cell aplasia (PRCA) were investigated using the technique of in vitro hematopoiesis and an assay for human parvovirus. Complement-dependent serum inhibitors against late erythroid progenitors (CFU-E) were demonstrated in seven of 19 patients examined, and complement-dependent inhibitors against early erythroid progenitors (BFU-E) were demonstrated in three of these seven patients. Nonspecific and complement independent inhibitors against CFU-E were thought to be associated with the etiology of PRCA in one patient. Human parvovirus-mediated erythropoietic suppression was demonstrated in a patient with complete remission of acute lymphoblastic leukemia complicated with marrow erythroid aplasia, whose serum showed a perfect inhibition against erythroid progenitor cells. T-cell-mediated erythroid suppression was not demonstrated in the patients examined. These findings reveal that erythroid aplasia is associated with complement-dependent serum erythropoietic inhibitor in some patients (36.8% in the present study) with PRCA, but it is difficult to identify the mechanism of erythroid aplasia in more than half of the patients with PRCA. In addition, our present study discovered the presence of parvovirus-mediated marrow pure red cell aplasia in one adult patient with acute lymphoblastic leukemia. PMID- 1908709 TI - Purification and characterization of a bovine pregnancy-associated glycoprotein. AB - A 67000 Mr bovine pregnancy-associated glycoprotein (bPAG) has been isolated from fetal cotyledons and purified to homogeneity by HPLC. The purification was monitored by a double immunodiffusion test and by RIA in conjunction with an antiserum raised against a crude fraction of placenta-specific antigens. The molecular weight of bPAG was estimated to be 67000 by SDS-PAGE. The isoelectric points (pI) of the four isoforms, determined by high-resolution analytical electrofocusing in polyacrylamide gel, were 4.4, 4.6, 5.2, and 5.4. The carbohydrate content of the bPAG consisted of approximately 10.02 +/- 1.09% neutral sugar and variant amounts of sialic acid (from 0.29 +/- 0.06% in the most basic isoform to 2.1 +/- 0.31% in the most acidic isoform). A specific antiserum was raised against the purified bPAG. A specific RIA showed that the bPAG was antigenically unrelated to BSA, alphafetoprotein (AFP), and human schwangerschafts-spezifischen (pregnancy-specific) beta 1 glycoprotein (SP1). According to some characteristics (e.g. the molecular weight), the purified bPAG may correspond to a form of the pregnancy-specific protein B previously described by Sasser and colleagues (Biol Reprod 1986; 35:936-942). PMID- 1908711 TI - Chronic administration of estradiol produces a triphasic effect on serum concentrations of gonadotropins and messenger ribonucleic acid for gonadotropin subunits, but not on pituitary content of gonadotropins, in ovariectomized ewes. AB - To determine the acute and chronic effects of estradiol on synthesis and secretion of LH and FSH, ovariectomized ewes were administered estradiol via silastic capsules for 0 h, 12 h, 1 day, 2 days, 4 days, 8 days, 16 days, or 32 days (n = 5/group). Concentrations of GnRH in the median eminence began to decrease within 12 h and were lower (p less than 0.05) than in control ewes from 1 to 4 days after estradiol administration was begun. Serum concentrations of LH were decreased relative to pretreatment control levels from 1 to 10 h, elevated during a preovulatory-like surge from 11 to 22 h, and then decreased and remained below 1 ng/ml for the duration of the experiment. Serum concentrations of FSH followed a pattern similar to those for LH except that the magnitude of change was smaller. Treatment with estradiol initially (12 h) reduced (p less than 0.05) quantities of mRNA for alpha-, LH beta-, and FSH beta-subunits, after which the quantities of mRNA for the subunits returned to near or above control levels by Day 2. After 8 days of treatment the amounts of mRNAs for gonadotropin subunits were again less (p less than 0.05) than those of controls, and they remained suppressed through Day 32. Pituitary concentrations of LH and FSH decreased (p less than 0.05) during the first day of treatment and remained suppressed for the duration of the experiment. Thus, estradiol had a triphasic effect on secretion of gonadotropins and steady-state levels of mRNA for the gonadotropin subunits, but not on pituitary content of gonadotropins.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1908712 TI - Human chorionic gonadotropin increases the concentration of macrophages in neonatal rat testis. AB - The purpose of these studies was to determine whether treatment of newborn rats with exogenous FSH or hCG would alter the concentration or size of testicular macrophages. Animals were injected once daily with various doses of FSH, hCG, or vehicle for 8-10 days beginning the day following birth. After immunohistochemical labeling of the macrophages with a monoclonal antibody specific for rat macrophages, the concentration and size of macrophages were determined by use of a point-counting method. Body weight, testis weight, and serum levels of testosterone and FSH were also measured. It was found that hCG significantly increased the concentration of macrophages within the interstitium but did not affect the size of the cells. Both testicular weight and serum testosterone concentrations increased after hCG treatment. Although FSH increased the weight of the testis, neither the size nor concentration of macrophages was altered. These results raise the possibility that the number of macrophages within the interstitial compartment of the normally maturing rat testis is under the control of LH. PMID- 1908710 TI - Age-related changes in the function of the pituitary-gonadal axis in a sterile male rat mutant (hd/hd). AB - Testicular growth is depressed in the genetically sterile male rat (hd/hd) relative to its LE phenotype littermates (by 50% and 73% at 27 and 90 days of age, respectively). Within the hd/hd testis, both the tubular and seminiferous tubule tissues are affected by the mutation. In addition, there is significantly less germ cell production from the primary spermatocyte stage of spermatogenesis onwards and the total number of Sertoli cells observed is less. In the intertubular tissue, the total volume and the total number of Leydig cells per testis is significantly less, but the mean volume of an average Leydig cell is not modified. The serum gonadotropin levels are higher in the hd/hd rat, whereas from 40 days of age onwards the level of testosterone is lower. The FSH and LH binding affinity constants are unchanged by the mutation; however, the total number of FSH binding sites per 10(6) Sertoli cells is lower while that of LH per 10(6) Leydig cells is greater. Indeed, it is likely that the lesser concentration of serum testosterone in the hd/hd rat is a result of a smaller number of Leydig cells since their individual function is not modified. The testicular androgen binding protein (ABP) content and the ABP output towards the epididymis are lower as a consequence of both a lesser number and an altered function of the Sertoli cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1908714 TI - Characterization of thymosin alpha 1 and beta 4 during the bovine estrual period: effects of elevated estradiol and progestin. AB - At present, there is a renewed interest in thymic function and its secretions in relation to endocrine control and reproductive function. In an initial experiment, 60 crossbred heifers (18-20 mo) were detected in estrus and assigned to control or FSH superovulatory groups. On Days 7-14 of the subsequent estrous cycle, FSH was administered for 5 days and prostaglandin F2 alpha (PGF2 alpha) was administered at 48 and 60 h after the initial FSH injection. Control animals received only PGF2 alpha injections between Days 9 and 15 of the cycle. Blood samples were collected from all animals at the time of PGF2 alpha injection and every 12 h thereafter to 72 h post PGF2 alpha injection. In a subsequent experiment, 103 crossbred heifers (16-18 mo) were superovulated with FSH and synchronized to estrus with PGF2 alpha administered 60 h after the initial FSH injection. Twenty-eight of the heifers received Norgestomet implants 12 h prior to the initial PGF2 alpha injection to inhibit the LH surge. Blood samples were collected from animals at 12-h intervals until the PGF2 alpha injection and every 6 h thereafter until 108 h post PGF2 alpha treatment. Although thymosin beta 4 concentrations did change over the estrual period, no differences were noted between control and superovulatory animals in the initial experiment even though estradiol concentrations were increased tenfold from the FSH stimulated ovary. In the second experiment, thymosin beta 4 and alpha 1 increased as the estrual period progressed and decreased (p less than 0.05) subsequent to the LH surge. (ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1908713 TI - Localization of rabbit sperm acrosin during the acrosome reaction induced by immobilized zona matrix. AB - To better understand the loss of the acrosomal cap on the surface of the zona pellucida and the function of the equatorial-postacrosomal region after the acrosome reaction, we have constructed an in vitro system using heat-solubilized zonae pellucidae dried onto a coverslip and incubated with capacitated spermatozoa. This system allows good optical resolution of spermatozoonzona interaction. Induction of the acrosome reaction by zonae on coverslips (30%) is comparable to the induction of the reaction reported previously for rabbit spermatozoa using solubilized zonae in solution. Antiserum to rabbit proacrosin, antiserum to a porcine 49-kDa proacrosin fragment, and antiserum to a porcine 14 kDa C-terminal acrosin fragment were utilized to monitor the acrosome reaction. Rabbit proacrosin/acrosin is not present on the surface of live, acrosome-intact, swimming spermatozoa. After contact with zona, the acrosome reaction begins and proacrosin/acrosin becomes available to bind antibody, first as a crescent in the apical region and then more posteriorly until the entire anterior acrosome is labeled. Proacrosin/acrosin remains on the equatorial and postacrosomal regions of acrosome-reacted spermatozoa and also remains associated with the acrosomal cap even after the spermatozoon is no longer associated with it. Further studies using zona-coated coverslips should lead to a more detailed understanding of the mechanism of zona penetration. PMID- 1908715 TI - Maternal and fetal infection. AB - Although their incidence varies among populations, maternal-fetal infections are increasingly recognized to be among the most common causes of maternal and perinatal morbidity. The use of new techniques, including nucleic acid hybridization and direct fetal or trophoblastic cell sampling, continues to accelerate our knowledge of the epidemiology, microbiology, and immunology, as well as means to diagnose, treat, and prevent individual congenitally transmitted infections. Given the number and complexity of these infections, only selected aspects of recent advances are presented. PMID- 1908717 TI - Urologic surgical techniques. AB - Surgery for incontinence, other than genuine stress incontinence, is a small part of the general gynecologist's practice. He or she must maintain a high index of suspicion for diverticula and fistulae. Included here are several good review articles that outline the state of the art and include classic references in the bibliography. Patients with cancer with a genitourinary fistula and incontinence may be managed in a variety of ways. Percutaneous nephrostomy and occlusion of the distal ureter may be an option in patients with incurable disease. Continent diversion, such as the Indiana pouch, offers a long-term remedy to the appropriate patient, even one who has been irradiated, as reported by Mannel. Iatrogenic incontinence is distressing to the patient and her doctor. Webster and Kreder offer keen insight into the evaluation of patients who have postoperative, obstructive, voiding dysfunction. They describe an operative correction, the obturation shelf repair, quite similar to the paravaginal defect repair, which restores "normal anatomy" and results in excellent relief of voiding dysfunction in approximately 90% of their patients. Postoperative bladder care is of concern to the doctor, patient, and nursing staff. Noble's article on the timing of catheter removal is innovative and practical. PMID- 1908718 TI - [Bony bridges of the lumbar transverse processes]. AB - A traumatic osseous bridge between lumbar transverse processes is a bone formation occurring after severe or even mild trauma of the back. However, only few of the patients with a contusion of the back or a fracture of a lumbar transverse process develop such an osseous bridge. The localisation of the haematoma plays an important role in this process, but myositis ossificans is a mandatory condition. Anamnesis will not lead to traumatic aetiology in all cases, because sometimes the patient is not aware of the fact that a transverse process has been fractured. The diagnosis finally depends on the recognition of the different shapes. The traumatic osseous bridge is characterised by the kind of trauma that causes the fracture of the transverse process. The shapes can be classified as "h", "H", "K", or "Z". Among 72 patients with inter-transverse osseous bridges, only 11 patients have congenital bridges. The congenital osseous bridge shows typical features that can be explained by means of embryogenic and functional dynamic considerations. These symptoms are the O-shape, concavity of the lumbar spine of a pathological nature and the absence of degenerative changes in the corresponding intervertebral space. PMID- 1908716 TI - Subdermal progestin implant contraception. AB - Sustained-release progestin contraceptives are a new approach to meeting a worldwide need for more effective and acceptable birth control. These contraceptive systems provide low, stable levels of synthetic progestins for periods of months to several years. Unlike earlier injectable and oral contraceptives, they do not cause peaks in progestin levels beyond those required for effective contraception, nor do they employ estrogens. For these reasons, sustained-release progestin systems are without some of the health risks attributed to birth control pills, and they are more effective, as well as easy to use, and completely reversible. They share common side effects, the most frequent of which is irregular menstrual bleeding caused by the erratic shedding of hypotrophic endometrium. Despite this and other minor side effects, most users find the sustained-release systems acceptable alternatives to other methods of contraception. Permanent or biodegradable subdermal implants, injections, intrauterine and intracervical devices, and vaginal rings are all employed as delivery systems for contraceptive progestins. The Norplant (Wyeth Ayerst, Radnor, PA) system, consisting of six silastic tubes filled with levonorgestrel and implanted under the skin, was recently approved by the US Food and Drug Administration and is already used by more than a half million women worldwide. The other sustained-release systems are in various stages of development, at least several years away from general use. When these new methods complete clinical trials, women will be able to choose from among implants, injections, or pellets with various durations of action, all providing convenient, highly effective contraception with low risk to health. PMID- 1908719 TI - [Lipid peroxidation and blood gas contents during ozone therapy in post resuscitation period]. PMID- 1908720 TI - ["Masked" autoantibodies from the serum of healthy blood donors cross-reacting with DNA and bacterial lipopolysaccharides]. AB - The "masked" autoantibodies with polyspecific activity were found in the serum of healthy donors. It is shown that these antibodies are able to react with antigens after the ion exchange chromatography with QAE-sephadex. It was found that these "masked" antibodies are able to cross-react with DNA and lipopolysaccharides of wide-spread species of bacteria. The possible role of these antibodies as in protection of organism from the external antigens as in the origin of autoimmune diseases is discussed. PMID- 1908721 TI - [Determination of antibodies to cross-reacting antigens of microorganisms in oncological diseases]. AB - It was studied antibodies to saprophytic microorganism Bacillus megaterium H glycoprotein in healthy, oncological, non-oncological gastrointestinal patients and animals. High level of antibodies to microbial glycoprotein in blood sera was revealed in cancer and precancer patients. Analogical results were obtained in mice A/Sn and Balb/c with inductive or transplanted tumors. It has been suggested the use of Bacillus megaterium H glycoprotein (M. m. 65-70 kD) for immunological monitoring. PMID- 1908722 TI - Identification of Gz alpha as a pertussis toxin-insensitive G protein in human platelets and megakaryocytes. AB - G proteins mediate the interaction between cell surface receptors and intracellular effectors. Recent studies have shown that human retina and rat brain contain mRNA encoding a novel 40-Kd G protein alpha subunit referred to as Gz alpha. Studies with an antiserum selective for the predicted sequence of this protein have suggested that a similar protein is present in human platelets and is phosphorylated during platelet activation. To better understand the structure and function of this protein, the present studies examine its sequence in platelets and compare its abundance in human platelets, megakaryocytes, and two megakaryoblastic cell lines, HEL cells and Dami cells. Three different Gz alpha selective antisera reacted with a 40-Kd protein in platelet membranes. None of these detected a corresponding protein in HEL or Dami cells, despite the presence in both cell lines of proteins recognized by antisera selective for three members of the Gi alpha family. Northern blotting with a Gz alpha-specific probe prepared from retinal Gz alpha showed two hybridizing species in platelet RNA: a major band at 3.5 kb and a minor band at 2.2 kb. Both were detectable in HEL and Dami cells, but at greatly reduced levels compared with platelets. RNA encoding Gz alpha was also detected in individual human megakaryocytes by in situ hybridization. The amount present approached that of Gi alpha 2' the most abundant of the Gi alpha species present in platelets. The complete sequence of the platelet homolog to Gz alpha was determined from platelet RNA amplified by the polymerase chain reaction. The encoded protein was the same as those obtained in brain and retina. Thus, based on immunoreactivity and nucleotide sequencing, platelets and megakaryocytes contain substantial quantities of a protein identical to brain and retinal Gz alpha. The paucity of Gz alpha protein and RNA in the megakaryoblastic cell lines suggests that either there has been a selective loss of the ability to synthesize Gz alpha from these cells or that Gz alpha appears at a later stage in megakaryocyte development than does Gi alpha. PMID- 1908723 TI - Interleukin-9 expression in human malignant lymphomas: unique association with Hodgkin's disease and large cell anaplastic lymphoma. AB - To test the possibility that interleukin-9 (IL-9), the human homologue of the mouse T-cell growth factor P40, may be involved in the pathogenesis of human lymphomas, we examined IL-9 expression in a variety of tumors both by Northern blot analysis and by in situ hybridization. Of 18 B-cell non-Hodgkin's lymphomas and 11 peripheral T-cell lymphomas, none expressed IL-9 message. By contrast, IL 9 message was found in two of six cases of large cell anaplastic lymphoma (LCAL) and in 6 of 13 cases of Hodgkin's disease (HD). In HD the strongest signals were observed in Hodgkin (H) and Sternberg-Reed (SR) cells, but IL-9 mRNA was also detected in small lymphocytic cells. A search for IL-9 message in a panel of 20 cell lines derived both from hematopoietic and nonhematopoietic tumors confirmed the unique association of IL-9 expression with HD and LCAL in as much as the only two cell lines with IL-9 message were derived from cases of HD and LCAL. These results suggest that IL-9 is not involved as an autocrine growth factor in the pathogenesis of most B- and T-cell lymphomas, but that it may play a role in HD and LCAL. PMID- 1908724 TI - Future of long term care of dependent elderly people. PMID- 1908725 TI - Bone marrow transplantation for severe aplastic anaemia: cost/benefit of increased immunosuppression. PMID- 1908726 TI - Graft versus host disease prophylaxis today. PMID- 1908727 TI - Results of T-depleted BMT in chronic myelogenous leukaemia after a conditioning regimen that included thiotepa. PMID- 1908728 TI - Bone marrow transplantation for metabolic diseases with severe neurological symptoms. PMID- 1908729 TI - Recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF) reduces infection-related mortality after allogeneic T-cell depleted BMT. PMID- 1908730 TI - Effects of ATP-sensitive K+ channel blockers on the action potential shortening in hypoxic and ischaemic myocardium. AB - 1. In order to determine whether activation of adenosine triphosphate (ATP) sensitive K+ channels exclusively explains the hypoxia- and ischaemia-induced action potential shortening, effects of tolbutamide and glibenclamide on changes in action potential duration (APD) during hypoxia, metabolic blockade or experimental ischaemia were examined in guinea-pig and canine isolated myocardium by standard microelectrode techniques. 2. With use of patch clamp techniques, activity of ATP-sensitive K+ channels was recorded from open cell-attached patches of guinea-pig isolated ventricular myocytes. The probability of opening of the K+ channels was decreased by 2 mM tolbutamide and 20 microM glibenclamide to almost the same extent, whereas it was increased by 100 microM pinacidil. 3. In guinea-pig papillary muscles a marked shortening of the action potential produced by 100 microM pinacidil was completely antagonized by 2 mM tolbutamide or 20 microM glibenclamide. 4. In guinea-pig papillary muscles exposed to hypoxic, glucose-free solution or dinitrophenol (10 microM)-containing, glucose free solution, APD declined gradually and twitch tension decreased. Pretreatment with glibenclamide partially but significantly inhibited the action potential shortening, whereas tolbutamide failed to improve it during hypoxia or metabolic blockade. 5. When in canine isolated myocardium, experimental ischaemia was produced by the cessation of coronary perfusion, APD was gradually shortened. The action potential shortening was partially but not completely inhibited by pretreatment with 20 microM glibenclamide. 6. These results suggest that changes in membrane current(s) other than the outward current through ATP-sensitive K+ channels also contribute to the action potential shortening in hypoxic or ischaemic myocardium. PMID- 1908731 TI - Involvement of capsaicin-sensitive nerves in the bronchomotor effects of arachidonic acid and melittin: a possible role for lipoxin A4. AB - 1. Functional studies have been performed to evaluate the potential involvement of capsaicin-sensitive nerves in the bronchomotor responses evoked by lipid mediators produced from the metabolic breakdown of arachidonic acid (AA) in the guinea-pig bronchus. 2. In the presence of indomethacin, the exogenous administration of AA (0.01-1 mM) produced a concentration-dependent contractile response in guinea-pig isolated bronchial rings. AA-induced contractions were augmented by epithelium-removal and by thiorphan (10 microM), an inhibitor of tachykinin breakdown. A sustained downward and rightward displacement of the complete concentration-response curve to AA was observed after in vitro capsaicin desensitization. 3. BWA4C (1 microM), a selective inhibitor of 5-lipoxygenase, shifted the AA concentration-response curve to the right. In the presence of this inhibitor, capsaicin desensitization did not have any further inhibitory action. 4. A potent, concentration-dependent and capsaicin-sensitive bronchoconstrictor effect was also observed with the polypeptide, melittin (10 nM-1 microM), an activator of phospholipase A2, which therefore should generate endogenous AA. 5. In vitro capsaicin-desensitization produced a significant reduction of the bronchomotor responses evoked by lipoxin A4 (1-6 microM), but not of those elicited by other lipoxygenases products such as leukotriene D4 (1-100 nM) or by 15-hydroxyeicosatetraenoic acid (15-HETE, 1-6 microM). 6. These findings indicate that lipoxin A4 but not leukotriene D4 or 15-HETE, might be one of the lipoxygenase mediators of excitatory effects of AA on capsaicin-sensitive sensory nerves. PMID- 1908732 TI - Bioassay of nitric oxide released upon stimulation of non-adrenergic non cholinergic nerves in the canine ileocolonic junction. AB - 1. The release and the nature of the inhibitory non-adrenergic non-cholinergic (NANC) neurotransmitter was studied in the canine ileocolonic junction. A circular muscle strip of the canine ileocolonic junction served as donor tissue in a superfusion bioassay in which rings of rabbit aorta with the endothelium removed served as detector tissue. 2. The ileocolonic junction released a labile factor with vasodilator activity upon stimulation of non-adrenergic non cholinergic (NANC) nerves in response to electrical impulses and the nicotinic receptor agonist 1,1-dimethyl-4-phenylpiperazinium (DMPP). This release was respectively frequency- and concentration-dependent. 3. The release was reduced by the blocker of neuronal conductance, tetrodotoxin, and by the inhibitor of the nitric oxide (NO) biosynthesis NG-nitro-L-arginine. The biological activity was enhanced by superoxide dismutase and eliminated by haemoglobin. Hexamethonium abolished only the release in response to DMPP. 4. Injection of adenosine 5' triphosphate (ATP) or vasoactive intestinal polypeptide (VIP) onto the cascade induced relaxations of the rabbit aorta but they were different from those induced by NO or the transferable factor. 5. Based on organ bath experiments in which the reactivity of different parts of the circular smooth muscle layer of the ileocolonic junction was investigated, a muscle strip of superficial circular muscle with submucosa was chosen as the detector strip in the bioassay cascade. 6. The ileocolonic junction dose-dependently relaxed in response to nitroglycerin and NO. NO was much more potent in the rabbit aorta than in the canine ileocolonic junction. 7. In conclusion, our results demonstrate the release of a transferable vasorelaxant factor in response to NANC nerve stimulation which behaves pharmacologically like NO but not like ATP or VIP. Therefore, we suggest that NO or a NO releasing substance is the inhibitory NANC neurotransmitter in the canine ileocolonic junction. PMID- 1908733 TI - Evidence that acetylcholine-mediated hyperpolarization of the rat small mesenteric artery does not involve the K+ channel opened by cromakalim. AB - 1. Acetylcholine causes a concentration-dependent hyperpolarization of the rat small mesenteric artery (diameter at 100 mmHg, 200-400 microns). In the absence of tone the average potential change was from approximately -60 to -75 mV. In the presence of tone induced by endothelin-1 (20 nM), acetylcholine caused vasorelaxation in association with a marked hyperpolarization; from approximately -32 to -71 mV. 2. A number of compounds known to antagonize the actions of cromakalim were tested for their ability to block responses to acetylcholine. Glibenclamide (0.1-3 microM), phentolamine (10-100 microM) and alinidine (1-30 microM) caused a concentration-dependent depolarization of the rat small mesenteric artery which was not dependent on an intact endothelium. Glibenclamide was approximately 10 times more potent than either phentolamine or alinidine, a similar ratio to their potency as antagonists of cromakalim. 3. In the presence of concentrations of the cromakalim antagonists which functionally inhibited responses to cromakalim, only phentolamine and alinidine had a significant effect on the hyperpolarization and functional responses to acetylcholine. Glibenclamide was without effect at the concentrations used. 4. Experiments on pig coronary artery, where acetylcholine causes vasoconstrictor responses, showed that phentolamine and alinidine have some anti-muscarinic activity which could account for their ability to affect vasorelaxant/hyperpolarization responses to acetylcholine in the rat small mesenteric artery. 5. The results suggest that the acetylcholine-mediated hyperpolarization observed in the rat small mesenteric artery does not involve K+ channels opened by cromakalim. This finding differs from other studies performed on the rabbit middle cerebral artery which show hyperpolarizing responses to acetycholine to be glibenclamide-sensitive. It is likely therefore that the hyperpolarization response observed to acetylcholine can be initiated through a number of mechanisms, only one of which utilizes K+ channels opened by cromakalim. PMID- 1908734 TI - The effect of inhibitors of the L-arginine/nitric oxide pathway on endotoxin induced loss of vascular responsiveness in anaesthetized rats. AB - 1. The effects on blood pressure and on pressor responses to noradrenaline (NA), of NG-monomethyl-L-arginine (L-NMMA) and NG-nitro-L-arginine methyl ester (L NAME), inhibitors of the L-arginine/nitric oxide pathway, were investigated in anaesthetized rats receiving an infusion of bacterial endotoxin (E. coli lipopolysaccharide, LPS). 2. Infusion of LPS (10 mg kg-1 h-1) for 50 min had no effect on mean arterial blood pressure (MABP) but induced a reduction in responsiveness to noradrenaline (100 ng-1 micrograms kg-1). L-NMMA (30 mg kg-1), but not D-NMMA, caused an increase in MABP of approximately 30 mmHg and restored responses to NA. This effect was reversed by L- but not D-arginine (100 mg kg-1). 3. In LPS-treated rats, blood pressure responses to NA were only marginally increased by the cyclooxygenase inhibitor, indomethacin (5 mg kg-1). L-NAME (1 mg kg-1) caused a similar increase in MABP and restored pressor responses to NA both in the presence and absence of indomethacin. 4. Co-infusion of vasopressin (100 ng kg-1, for 10 min) with LPS (10 mg kg-1 h-1) in order to reproduce the hypertensive effect of L-NMMA and L-NAME increased pressor responsiveness to 100 and 300 ng kg-1 NA but not to 1 microgram kg-1 NA. 5. Infusion of sodium nitroprusside (30 micrograms kg-1 min-1) decreased responsiveness to NA even when the hypotension was corrected by co-infusion of vasopressin (50 ng kg-1 min-1). 6. These results demonstrate that the restoration of vascular responsiveness to NA in LPS-treated anaesthetized rats by inhibitors of the L-arginine/nitric oxide pathway is stereospecific and reversible. Furthermore, the experiments involving indomethacin suggest that although cyclo-oxygenase products of arachidonic acid may contribute to the development of LPS-induced hyporeactivity, the effect of L NAME is unlikely to involve inhibition of the cyclo-oxygenase pathway. Comparison of NA responsiveness during vasopressin and L-NMMA/L-NAME-induced hypertension shows that increasing the blood pressure may modify LPS-induced hyporeactivity, but cannot account for the complete restoration of responses to NA by L-NMMA and L-NAME. These observations suggest that activation of nitric oxide formation from L-arginine makes a direct contribution to the production of vascular hyporeactivity by LPS in vivo. PMID- 1908736 TI - Blood gas and acid-base values in calves, sampled from the brachial and coccygeal arteries. AB - Blood samples were taken from the brachial and coccygeal arteries of young calves and blood gas and acid-base values determined. There was no significant difference in pH, PO2, PCO2 or HCO3- between sites as demonstrated by a paired t test (P greater than 0.05). Significant correlations between sites existed for individual values of PO2 (P less than 0.001), HCO3- (P less than 0.05) and pH (P less than 0.02), but not for PCO2. PMID- 1908735 TI - Demethoxyviridin and wortmannin block phospholipase C and D activation in the human neutrophil. AB - 1. The fungal metabolite, wortmannin, has recently been shown to inhibit fMet-Leu Phe-stimulated superoxide production and phospholipase D (PLD) activation in the human neutrophil. 2. We have found that a close structural analogue of wortmannin, demethoxyviridin, has a similar inhibitory profile but in addition blocks phosphatidylinositol 4,5-bisphosphate-specific phospholipase C and hence inositol 1,4,5-trisphosphate (IP3) formation. 3. Inhibition of fMet-Leu-Phe stimulated PLD by demethoxyviridin was characteristically non-competitive (IC50 = 31 +/- 10 nM). 4. Inhibition of fMet-Leu-Phe-stimulation IP3 formation required concentrations almost 10 times higher (IC50 = 250 +/- 130 nM). 5. Surprisingly, demethoxyviridin only inhibited fMet-Leu-Phe-induced intracellular calcium mobilization at concentrations 100 times greater than those needed to block IP3 formation. 6. Demethoxyviridin also inhibited PLD activation induced by sodium fluoride or phorbol myristate acetate (PMA) but the concentrations required were 100 times those needed to block fMet-Leu-Phe-stimulated PLD. 7. These observations support the contention that PLD plays an important role in signal transduction in the human neutrophil and indicate that wortmannin and demethoxyviridin inhibit PLD activation at a common step in the signalling pathway. 8. Furthermore, these results suggest that demethoxyviridin may block the interaction between the chemotactic peptide receptor and a GTP-binding protein that is intimately involved in PLD activation. PMID- 1908737 TI - [Modifications of sialylation in BHK 21/C13 cells after in vitro transfection by c-Ha-ras human oncogene]. AB - A Hamster kidney fibroblast cell line (BHK 21/C13) has been transfected by c-Ha ras human oncogene. The expression of the oncogene significantly modified the global sialytransferase activity of the cell extract. This activity is enhanced on an average 2.5 fold whatever the acceptor. In addition, the proportion of cell surface associated N-glycolylneuraminic acid is enhanced in transfectants, the ratio N-acetylneuraminic acid/N-glycolylneuraminic acid decreases from 7.10 to 2.80. These results suggest that a tight relationship exists, in c-Ha-ras transfected BHK cells, between the expression of the oncogene and the neuraminic acid metabolism as well as a gene regulation of glycoconjugate sialylation. PMID- 1908738 TI - [Production of a monoclonal antibody (B1N) recognizing human nuclear antigen associated with cell proliferation]. AB - This report describes the preliminary characterization of a novel antigen reactive with a murine monoclonal antibody designated B1N produced in our laboratory. This antibody (IgM) reacts in IFI with mammals and also insect cells, by staining in a speckled fashion the nucleus of these cells. Immunoblotting analysis of Hela and murine D55 nuclear extracts revealed a polypeptide with an apparent molecular weight of 120kD (p120). In this work we demonstrated that: 1. this polypeptide appeared in human peripheral blood lymphocytes only when they were induced to proliferate in vitro after phytohemagglutinin stimulation; 2. this polypeptide was no longer detected in D55 resting cells, following serum deprivation; 3. the MAb B1N specifically revealed the nucleus of proliferating cells on frozen sections of uterine tissue. These data strongly suggest that the p120 nuclear antigen expression is associated with the proliferation state of cells. PMID- 1908739 TI - Detection of HTLV-1 gag related sequences in leucocyte DNA from patients with polyendocrinopathies (Basedow-Graves' disease and insulin-dependent diabetes). AB - Relationships with retroviruses have recently been found in different human pathologies as autoimmune diseases which would be associated with the presence and eventually the expression of retroviral sequences. Detection of the presence of HTLV-1 and HIV-1 homologous sequences and their expression was realised on lymphocytes of 14 patients with polyendrocrinopathies (Basedow-Graves' disease and insulin-dependent diabetes) and four relatives of one index case. No antibodies to HTLV-1 and HIV-1 could be detected by Western blot and Elisa tests. HTLV-1 related sequences were revealed by Southern blot (SB) in 5 out of 18 subjects' DNA. Analyses of all DNA were performed by polymerase chain reaction (PCR). Seven DNA, including the 5 previously positive in SB, and two relatives (father and grandfather), negative in SB, contained HTLV-1-gag related sequences, but neither pol nor pX regions. Concerning HIV-1, all 18 DNA examined were negative by both methods. DNA of ten clinically healthy donors were found to be negative with the same tests. PMID- 1908740 TI - [Homologies between hemerythrins of sipunculids and cadmium-binding metalloprotein (MP II) from a polychaete annelid, Nereis diversicolor]. AB - The determination of the first 33 amino acids of the Cd-binding-protein (MP II) of Nereis diversicolor (Annelida, Polychaeta) shows a homology of 79 and 61% with 2 respiratory proteins of sipunculids, respectively the myohemerythrin and the hemerythrin. The positive reaction obtained by immunocytochemistry over the hemerythrocytes of Sipunculus nudus using antibodies raised against MP II and the presence of iron on the MP II reinforce this similarity. PMID- 1908741 TI - Intermolecular recombination of human c-myb proto-oncogene coding sequences. AB - We have previously reported evidence suggesting that intermolecular recombination events are involved in the tissue specific expression of the c-myb proto-oncogene in chicken. We show in this paper that recombined c-myb mRNA species are also expressed in human thymic cells, therefore indicating that intermolecular recombination of coding sequences occurs in higher eucaryotes. PMID- 1908743 TI - [Reactions to mirror in three species of lemurs (Lemur fulvus, L. macaco, L. catta)]. AB - Reactions when confronted with their own reflection in a mirror were observed in three captive groups of lemurs: L. fulvus, L. macaco and L. catta. The ability of a mirror to induce social facilitation of drinking was also studied in one individual of each species. As previously observed in monkeys, the three groups of lemurs showed much more attention to the mirror than to a non-reflective surface, especially nasal contacts. Only L. fulvus showed habituation to the mirror with successive presentations. No social behaviours were directed towards the reflection, in contrast to descriptions of mirror-image reactions in monkeys, and the mirror did not produce an effect of social facilitation. The results suggest that the mirror elicits a diminished social reaction in lemurs compared to monkeys, perhaps due to the absence of relevant olfactory stimuli. PMID- 1908742 TI - [Presence paf-acether mediator of inflammation in stools of patients with inflammatory enterocolitis]. AB - Paf-acether (platelet-activating factor, paf) is one of the most potent inflammatory mediators synthesised by and acting on most inflammatory cells. Paf causes gastric ulcerations and ischemic bowel necrosis. Recently, we described the presence of paf in stools of patients bearing ileal pouch-anal anastomosis with pouchitis. These findings prompted us to search for the presence of paf in stools of patients suffering from inflammatory bowel diseases: Crohn's disease and ulcerative colitis. The fraction corresponding to paf isolated from stools exhibited the same physicochemical and biological characteristics as synthetic paf. Reverse-phase high performance liquid chromatography revealed 80% of C16 and 20% of C18 paf. The presence of a biologically active phospholipid in human stools may bring new perspectives with respect to the study of gastrointestinal diseases as well as the use of paf antagonists in the treatment of inflammatory bowel diseases. PMID- 1908744 TI - Transformation of Neisseria gonorrhoeae: physical requirements of the transforming DNA. AB - The 1600-bp (base pair) fragment encoding a portion of the nalidixic acid resistant DNA gyrase, subunit B, was characterized to determine what parameters effect transformation in the gonococcus. When this DNA (pSY2) was isolated from Escherichia coli, it was able to transform a variety of gonococcal strains to resistance to nalidixic acid via DNA-mediated transformation, irrespective of their restriction-modification phenotype. Nalidixic acid resistant transformants contained no plasmid DNA sequences that corresponded to the vector, as measured by plasmid screening procedures and colony hybridization techniques. Supercoiled and linear DNA transformed the gonococcus at the same efficiency. DNA fragments as small as 615 bp were able to transform the gonococcus. The presence of a 10-bp uptake sequence enhanced a DNA fragment's ability to transform the gonococcus by four orders of magnitude. When the fragment encoding the nalidixic acid resistant DNA gyrase was subcloned into M13mp18, both the replicative form and the single stranded form of the phage were able to transform the gonococcus to nalidixic acid resistance. PMID- 1908745 TI - Immunoglobulin subclasses and prophylactic use of immunoglobulin in immunoglobulin G subclass deficiency. AB - Persistent low serum levels of one or several immunoglobulin G (IgG) subclasses can be found in a high proportion of adult patients with increased susceptibility to infections. It is hard to envision that the low subclass level in itself is responsible for this susceptibility because healthy blood donors have been described who are completely devoid of certain subclasses in serum. This apparent discrepancy may be partly explained by the observation that most subclass deficient patients have underlying aberrations in T-cell and B-cell interaction and function that may impair their capacity to compensate for even minor deficiencies. A prospective blind crossover study of the effect of prophylactic Ig substitution therapy was done in 43 adult patients with IgG subclass deficiency. The patients were randomized to receive 1 year of therapy with intramuscular Ig 25 mg/kg/wk or 1 year of saline injections. A significant protective effect of the prophylactic Ig therapy was seen with a great reduction in the number of days of infection. In addition, several immunologic parameters were altered after 1 year of Ig therapy. Nineteen of the patients later were included in an open study using 50 mg/kg/wk of Ig. After 6 months of treatment, significant protection against infection was observed, with a reduction of 6.2 days in the number of days per month with infection. This marked effect of prophylactic Ig suggests that the Ig aberrations seen in IgG subclass-deficient patients contributed to their susceptibility to infection. The effect of 25 mg/kg/wk was much less pronounced than that of 50 mg/kg/wk, and normal serum IgG subclass levels were not achieved even during the higher-dose therapy. However, it seems likely that subcutaneous or intravenous administration of larger doses of Ig would allow for more efficient therapy. PMID- 1908747 TI - In vitro study of cytotoxicity by U.V. radiation and differential sensitivity in combination with alkylating agents on established cell systems. AB - The effect of U.V. radiation or alkylating agents, such as actinomycin-D, cycloheximide and mitomycin-C (MMC), was studied on CHO, BHK and HeLa cells. U.V. radiation caused DNA ssb and dsb and were prevented by cycloheximide and actinomycin-D. MMC is known to be cytotoxic in CHO/BHK cells by forming free radical generation. MMC in combination with U.V. radiation enhanced DNA ssb & dsb in these cell types. However, HeLa cells were insensitive to U.V. radiation. This insensitivity to U.V. radiation could be ascribed to the presence of glutathione transferase which is absent in CHO/BHK cell line. PMID- 1908746 TI - Intratumoral low-dose interleukin-2 induces rejection of distant solid tumour. AB - This study shows that local tumor treatment with low-dose recombinant interleukin 2 (IL-2) can mediate rejection of a large distant solid tumour. When SL2 lymphoma cells were injected intraperitoneally (i.p.) in syngeneic DBA/2 mice on day 0.70% of these mice were cured by daily i.p. injections with 20,000 units IL-2 on days 10-14. After injecting mice with SL2 both i.p. and subcutaneously (s.c.) on the flank. 50% of the mice treated i.p. with low-dose IL-2 rejected both the i.p. tumour and the large distant s.c. tumour. In contrast, i.p. IL-2 treatment on days 10-14 cured fewer than 10% of the mice bearing only a s.c. SL2 tumour. The described IL-2 immunotherapy also caused systemic tumour rejection in mice bearing both ascitic and solid P815 mastocytoma. Thus it was shown that low-dose IL-2 can induce systemic tumour rejection, when injected at a site of tumour growth. Interleukin-2-induced rejection of s.c. SL2 tumour was highly specific, as mice that were rejecting i.p. and solid s.c. SL2 lymphoma did not reject solid P815 mastocytoma, which was injected s.c. simultaneously on the other flank. Furthermore, solid s.c. tumours consisting of mixtures of SL2 and P815 were not rejected in mice that rejected i.p. SL2 or P815. We conclude that intratumoral injections of low-dose IL-2 can enhance an ongoing weak immune reaction against the tumour resulting in systemic tumour rejection. PMID- 1908749 TI - [Relationship between hemodynamics and hemorrheology in chronic cor pulmonale]. AB - Hemodynamics, hemorrheology and blood gases were studied in 20 patients with stable chronic cor pulmonale. Blood viscosity was affected by hematocrit and blood gases, which acted on pulmonary pressure, pulmonary vascular resistance and right cardiac output. Blood viscosity was measured in the shear stress rate of 5.75, 11.5, 23, 46, 115 and 230 s-1. The decrease in plasma pH and PaO2 elevated high shear stress blood viscosity, pulmonary arterial pressure, total pulmonary vascular resistance and decreased right cardiac output, O2 administration decreased in high shear stress blood viscosity, but increased in low shear stress blood viscosity. Blood viscosity was positively correlated with hematocrit, which varied in different shear stress rate, the relative coefficient was the highest when the shear stress rate was in 11.5 s-1 (r = 0.9288 P less than 0.001). Pulmonary arterial pressure and pulmonary vascular resistance were positively correlated with high shear stress blood viscosity but uneffected by low shear stress blood viscosity. The increasing in high shear stress blood viscosity decreased the right cardiac output. Rigidity of red blood cell may play an important role in regulating pulmonary circulation and right heart function. PMID- 1908748 TI - Nanos is the localized posterior determinant in Drosophila. AB - Segmental pattern in the Drosophila embryo is established by two maternal factors localized to the anterior and posterior poles of the egg cell. Here we provide molecular evidence that the localized posterior factor is the RNA of the nanos (nos) gene. nos RNA is localized to the posterior pole of early embryos, and nos protein acts at a distance to direct abdomen formation. Synthetic nos RNA has biological activity identical to that of the posterior pole plasm. Injection of nos RNA rescues the segmentation defect of embryos derived from females mutant for all nine known posterior group genes. Injection of nos RNA into the anterior is able to direct formation of ectopic posterior structures. Our results demonstrate that a localized source of nos RNA is sufficient to specify abdominal segmentation and imply that other posterior group genes are required for localization, stabilization, or distribution of the nos gene product. PMID- 1908750 TI - The stability of mesna in beverages and syrup for oral administration. AB - We evaluated the stability of the aqueous formulation of mesna during storage in syringes and after dilution in beverages and syrups. Measurements of the concentrations of mesna showed that the undiluted formulation was stable for at least 9 days in standard polypropylene syringes at 5 degrees, 24 degrees, and 35 degrees C. There was no detectable oxidation of mesna to dimesna over the course of at least 1 week when mesna was diluted 1:2 and 1:5 in syrups and incubated at 24 degrees C in capped tubes. Concentration changes were clinically negligible for 1:2, 1:10, and 1:100 dilutions of mesna in six carbonated drinks, two juices, and milk after incubation for 24 h at 5 degrees C. Thus, the aqueous mesna formulation is stable when diluted and stored in a variety of beverages and syrups under conditions suitable for oral administration. PMID- 1908751 TI - Alternating chemotherapy in advanced gastric cancer. A phase II study. AB - A phase II study with an alternating chemotherapeutic scheme, in advanced gastric cancer was conducted. Twenty-two patients were treated with cisplatin and mitomycin C on day 1 and BCNU and doxorubicin on day 28. Tegafur p.o. was given daily from the start to the end of chemotherapy. This scheme was repeated every four weeks. Response rate was 25% (2 complete and 3 partial). However, remissions were short lived, and median survival for the entire group was 7 months. Haematological and gastrointestinal toxicities were severe. In conclusion, the low response rate and the high toxicity of this regimen preclude its use for the treatment of gastric cancer. PMID- 1908752 TI - Language-apparent reflex epilepsy. AB - An adolescent with photosensitive epilepsy had absence seizures reproduced by forced voluntary eye closure in light or in darkness, independent of eyelid immobilization or ocular elevation. Attacks preferably occurred while speaking Spanish, her second language, mediated through brief, strong, automatic closing of the eyes during difficult word retrieval. Complex other multidirectional ocular movements or blinking, cognitive and language tasks were ineffective. Frontorolandic cortical epileptogenesis is seemingly responsible for light provoked seizures in Papio papio, acting via hyperexcitable neuronal facial aggregates (i.e. Baba and Wada). Since orbicularis oculi muscle fibers mediating strong and weak contractions are differentially innervated by the facial nuclei, we submit that critical threshold tonic activation of specific nuclear aggregates explains this language-apparent reflex epilepsy, triggered by extreme eye closure. A "dopamine connection hypothesis" linking periodic eye closure, effortful memory and photosensitivity, based on its putative evolutive significance, is discussed. PMID- 1908753 TI - The relation between pharmacokinetics and endocrine effects of buserelin implants in patients with mastalgia. AB - Six patients with mastalgia were treated with polylactide/glycolide 50:50 implants containing 6.6 mg buserelin once every 4 weeks, to study the relationship between buserelin pharmacokinetics and suppression of pituitary ovarian function. On the first treatment day there was an initial rise in plasma and urinary buserelin levels followed by a rapid fall during the next 2 days. After a plateau phase (60-80 micrograms/g creatinine) urinary buserelin/creatinine ratios decreased slowly to a mean value of 25 micrograms/g creatinine 4 weeks after implantation. Plasma oestradiol concentrations dropped to castrate values within 2 weeks of treatment reaching a mean concentration of 17 pmol/l compared to 27 pmol/l (P less than 0.01) determined in 680 postmenopausal control women. After the last implant injection urinary buserelin/creatinine ratios remained relatively high (greater than 5 micrograms/g creatinine) during more than 8 weeks followed by an exponential decrease (half life of buserelin release: 15 days) to undetectable buserelin levels at 16-22 weeks after the last implantation. A rise of suppressed plasma oestradiol concentrations to above castrate levels was found 15-20 weeks after the last buserelin implantation, at a time when urinary buserelin excretion had decreased below 0.2 micrograms/g creatinine. It is concluded that after initial suppression of pituitary-ovarian function only very low concentrations of buserelin are needed to maintain suppression of ovarian activity by using slow release preparations. PMID- 1908754 TI - Attenuation of gonadotrophin release and reserve in superovulated women by gonadotrophin surge attenuating factor (GnSAF). AB - In-vivo and in-vitro studies have provided evidence that a non-steroidal ovarian factor, called gonadotrophin surge attenuating factor (GnSAF), attenuates the endogenous LH surge in superovulated women. To study the mechanism of action of GnSAF, the LH response to two i.v. pulses of GnRH (10 micrograms each, 2 h apart) was investigated in eight normally ovulating women during the late follicular phase of a spontaneous and an FSH superovulated cycle. The maximal LH increase in response to the first pulse (initial release) was considered as representing the acutely releasable pool and the delta LH area under the whole curve (integrated response) the reserve pool of LH. Both the initial release and the integrated response to GnRH were markedly attenuated in the FSH as compared to the spontaneous cycles. The response to the second pulse was significantly greater than the response to the first pulse (self-priming effect of GnRH) in both the spontaneous and the FSH cycles. However, in the FSH cycles the self-priming effect of GnRH was markedly reduced as compared to the spontaneous cycles. We conclude that during superovulation induction in women the two pools of pituitary LH are markedly attenuated. It is suggested that GnSAF attenuates both the GnRH induced initial release of LH and the self-priming effect of GnRH on the pituitary. PMID- 1908757 TI - Cardiac rehabilitation services: what are they and are they worth it? AB - The objectives of cardiac rehabilitation include lowering mortality but, more importantly, increasing functional capacity so reducing disability and potentially improving quality of life. The data suggest that cardiac rehabilitation services are worth the patient's costs and efforts and as such, they should be considered an integral component of comprehensive cardiovascular care by cardiologists and primary care physicians. While there is considerable agreement on the roles of exercise testing and training in the three position stands, there are also substantiated, and important, differences in their recommendations on other cardiac rehabilitation services, such as counseling and risk factor management. The challenge for the 1990's is not only to continue to better define the effectiveness of cardiac rehabilitation services, but more urgently, how to deliver effective services most efficiently. This will help physicians provide optimum care for their patients, will improve the patient's likelihood of regaining for themselves an active and productive life, and should generate a more equitable and accountable reimbursement system for quality health care. PMID- 1908755 TI - An updated comparison of drug dosing methods. Part III: Aminoglycoside antibiotics. AB - Aminoglycoside antibiotics continue to be useful for the treatment of Gram negative infections. Available dosing methods include predictive algorithms and nomograms, pharmacokinetics-based dosing methods, and methods that incorporate Bayesian forecasting. The individualised Sawchuk-Zaske and Bayesian methods have been extensively evaluated since the previous review in the Journal. Both methods continue to be rapid and accurate means of individualising dosage requirements for patients with diverse pharmacokinetic profiles. The predictive performance of the Bayesian method can be further enhanced when population-based parameters reflect the patient population being monitored. There are now several cost effectiveness studies that demonstrate that pharmacokinetic dosing services for aminoglycosides result in cost savings, better therapeutic concentrations, fewer toxic serum concentrations, and shorter mean durations of hospital stay and aminoglycoside therapy. Further studies are needed for cost-effectiveness and comparison of various dosing methods in paediatric and neonatal patients. PMID- 1908756 TI - Pharmacokinetic analysis of azelaic acid disodium salt. A proposed substrate for total parenteral nutrition. AB - Azelaic acid was the first dicarboxylic acid proposed as an alternative energy substrate in total parenteral nutrition. In this study, the pharmacokinetics of azelaic acid were investigated in 12 healthy volunteers, 7 receiving a constant infusion (10g over 90 min) and 5 a bolus dose (1g). The 24h urinary excretion and plasma concentration in blood samples taken at regular intervals were assayed by gas-liquid chromatography. Experimental data were analysed by a 2-compartment nonlinear model that describes both tubular secretion and cellular uptake in Michaelis-Menten terms. A high value of urinary excretion (mean 76.9% of infused dose) and a mean clearance of 8.42 L/h were found, suggesting the presence of tubular secretion. Estimating the population mean of the pharmacokinetic model parameters gave a maximal cellular uptake of 0.657 g/h. The model predicts that 90% of the maximal uptake should be reached in the plateau phase of a constant infusion of 2.2 g/h. The presence of extensive and rapid losses through urinary excretion, and the low estimated value of the maximal cellular uptake, indicate that azelaic acid is not suitable as an energy substrate for total parenteral nutrition. PMID- 1908758 TI - Encephalitic listeriosis in two adult llamas (Lama glama): clinical presentations, lesions and immunofluorescence of Listeria monocytogenes in brainstem lesions. AB - Encephalitic listeriosis was diagnosed in 2 adult llamas. Both had a multifocal suppurative encephalitis with mixed lymphocytic and neutrophilic perivascular infiltrates. Listeria monocytogenes was cultured from the brain stem of 1 llama using cold enrichment techniques; the other llama was culture negative. Formalin fixed and paraffin embedded sections of brainstem lesions from both affected animals were labeled with a fluorescein-conjugated, anti-L. monocytogenes antibody. Using this technique, intralesional L. monocytogenes were identified in both llamas. PMID- 1908759 TI - Preventive and therapeutic effects of lithium carbonate on acute radiation injury of hemopoietic system in mice. AB - The administration of Li2CO3 to female LACA mice for three consecutive days before or after 4Gy whole body gamma-irradiation appeared to have both preventive and therapeutic effects on radiation-induced leucopenia, especially on the depression of CFU-GM. It is effective in small dosage, short course, and even when given 24 hours after irradiation. PMID- 1908760 TI - Histological classification of schistosomal egg induced polyps of colon and their clinical significance. An analysis of 272 cases. AB - 272 cases of schistosomal egg induced polyps collected from mass-screening for colorectal carcinoma in Jiashan County were divided into 3 types: fibrous type (FT), mixed type (MT) and epithelial proliferative type (ET). The ET was characterized by crypt elongation, hypertrophy, variation in size, disorderly arrangement, as well as the high percentage of atypical hyperplasia (64.9%). The coexistence and transition between inflammatory reactive hyperplastic and neoplastic crypts were noticed. By HID/AB staining, sialomucins were increased in ET, CEA and PNA receptors detected by the ABC method were present in 18/20 and 6/18 of ET respectively. The mucin expression of ET was similar to that of adenomas. It is likely that a spectrum of ET, atypical hyperplasia and adenoma may exist. We suggest that the patients with ET, especially those with atypical hyperplasia, should be regarded as "risk group", and close follow-up is needed. PMID- 1908761 TI - Specific targeting of mitomycin C to tumors by anti-gastric cancer monoclonal antibody. AB - In the present study, an anti-gastric cancer monoclonal antibody, MGb2, was chosen to prepare antibody-mitomycin C (MMC) conjugate with dextran T-40 as intermediary. Twenty molecules of MMC were introduced into each molecule of antibody while the antigen-binding capacity of the antibody was kept well. The conjugate showed selective cytotoxicity upon human gastric cancer cell line SGC 7901. Radioimmunoimaging and biodistribution studies indicated that after conjugation with MMC via dextran T-40 as intermediary, the tumor localization capacity of the antibody was well retained. When tested in nude mice, inoculated with human gastric carcinoma SGC-7901 in bilateral subrenal capsules, intraperitoneal injection of the conjugate daily for 6 days at a dose of 1 mg/kg gave a tumor inhibitory rate of 68.67%, which was far better than that of free MMC or irrelevant conjugate. No synergetic effect was found in regard to the mixture of MGb2 with MMC. PMID- 1908762 TI - Lumbar intervertebral disc prosthesis. An experimental study. AB - To provide a more effective treatment and improve the outcome of surgical treatment of lumbar intervertebral disc protrusion, the values of lumbar intervertebral disc prosthesis (LIDP) were investigated. LIDP was specially designed and made of silicone rubber. The properties of material mechanics were investigated by compressive test and damage test of LIDP specimens. The biocompatibilities of LIDP were observed experimentally in monkeys. The surgical applicabilities were studied by in vitro experiments of fresh human lumbar spine. The results showed that LIDP has the advantages of good biomechanical applicability, biocompatibility and surgical applicability. LIDP is able to maintain the intervertebral space, stress balance and stability of the lumbar spine. after lumbar intervertebral disc excision, the replacement of LIDP could restore the functions of the lumbar spine and improve the curative results of disc excision. PMID- 1908763 TI - Survey on use of antimicrobial agents and bacterial resistance in Huashan Hospital. AB - A cross-section study was carried out to assess the general patterns in use of antimicrobial agents and the trends of bacterial resistance in Huashan Hospital. Of 2,400 patients whose charts were reviewed, 61% were given such drugs. 3,596 antibiotic courses were prescribed. Gentamicin was most frequently used. Results of the susceptibility test of 320 bacterial strains showed a high percentage of resistance against gentamicin, ampicillin, and chloramphenicol. Our findings suggest that antibiotic policies in the hospital need reappraising. PMID- 1908765 TI - Recent laboratory investigations by Chinese workers on antischistosomal activities of praziquantel. PMID- 1908764 TI - Hepatic carcinoma. The possibility of transcatheter chemoembolization through the portal vein. AB - A suspension of iodized oil and anticancer agent was injected into the portal veins of 20 rats with hepatic carcinoma and of 20 normal rats to observe its distribution in the liver and the effect on cancer tissue and normal cells. Microscopic and transmission electron microscopic examinations were carried out. Oil drops were seen in tumor cell lines, small blood vessels inside the cancer nest, the sinusoids, and the central veins. More oil drops were found in the peripheral parts of the tumor than in the central part. The distal small vessels were embolized with necrotic change of tumor cells and their subordinate normal liver cells. We conclude that portal vein part takes in the blood supply of liver cancer and tumor cell necrosis can be achieved after administration of iodized oil and anticancer agent mixture through the portal vein. Hence transcatheter treatment through the portal vein may be helpful as a supplement to intraarterial treatment of primary liver cancer and transcatheter embolization via the portal vein to reinforce the intraarterial therapy may be recommended. This procedure may cause necrosis of normal liver cells and care must be taken in clinical application. PMID- 1908766 TI - Statistics, CPT, ICD-9, CDM, and level III codes: what are they and how did I get this job? PMID- 1908767 TI - Changes in plasma and urinary amino acid levels during diabetic ketoacidosis in children. AB - Plasma and urinary concentrations of different amino acids were investigated during diabetic ketoacidosis (DKA) and 12, 24, 72 hours after initiation of therapy. In DKA, plasma concentration of glutamic acid, aspartic acid, valine, leucine and isoleucine significantly increased while that of asparagine and glutamine decreased compared to levels in well-controlled diabetic patients. The urinary excretion of branched-chain amino acids, histidine, serine and threonine was elevated while those of glutamic acid, glutamine, glycine and taurine were reduced. Among the different amino acids, histidine excretion had the highest variability. A strong correlation was found between the urinary excretion of several amino acids and that of the beta-2-microglobulin characterizing tubular dysfunction. Changes in the excretion of different amino acids reflect the altered metabolic state and renal function due to DKA. PMID- 1908768 TI - [The effect of free radical scavengers on electrophysiological characteristics in ischemia reperfusion rats]. PMID- 1908769 TI - An extensive 3' cis-regulatory region directs the imaginal disk expression of decapentaplegic, a member of the TGF-beta family in Drosophila. AB - The decapentaplegic (dpp) gene in Drosophila melanogaster encodes a TGF-beta-like signalling molecule that is expressed in a complex and changing pattern during development. One of dpp's contributions is to proximal-distal outgrowth of the adult appendages, structures derived from the larval imaginal disks. Appendage specific mutations of dpp fall in a 20 kb interval 3' to the known dpp transcripts. Here, we directly test the hypothesis that these mutations define an extended 3' cis-regulatory region. By analysis of germ-line transformants expressing a reporter gene, we show that sequences from this portion of the gene, termed the dppdisk region, are capable of directing expression comparable to that defined by RNA in situ hybridization. We localize two intervals of the dppdisk region that appear to account for much of the dpp spatial pattern in imaginal disks and discuss the positions of these important elements in terms of the genetics of dpp. Finally, we provide evidence to suggest that one of our constructs expresses beta-galactosidase in the early imaginal disk primordia in the embryo, at approximately the time when they are set aside from surrounding larval epidermal tissues. Thus, dpp may be involved directly in the determination of the imaginal disks. PMID- 1908770 TI - The interaction of boar sperm proacrosin with its natural substrate, the zona pellucida, and with polysulfated polysaccharides. AB - Boar sperm acrosin is an acrosomal protease with trypsin-like specificity, and it functions in fertilization by assisting sperm passage through the zona pellucida by limited hydrolysis of this extracellular matrix. In addition to a proteolytic active site domain, acrosin binds the zona pellucida at a separate binding domain that is lost during proacrosin autolysis. In this study, we quantitate the binding of proacrosin to the physiological substrate for acrosin, the zona pellucida, and to a non-substrate, the polysulfated polysaccharide fucoidan. Binding was analogous to sea urchin sperm bindin that binds egg jelly fucan and the vitelline envelope of sea urchin eggs. Proacrosin was found to bind to fucoidan and to the zona pellucida with binding affinities similar to bindin interaction with egg jelly fucan. These interactions were competitively inhibited by similar relative molecular mass polysulfated polymers. Since bindin and proacrosin have distinctly different amino acid sequences, their interaction with acidic sulfate esters demonstrates an example of convergent evolution wherein different macromolecules localized in analogous sperm compartments have the same biological function. From cDNA sequence analysis of proacrosin, this binding may be mediated through a consensus sequence for binding sulfated glycoconjugates. Proacrosin binding to the zona pellucida may serve as both a recognition or primary sperm receptor, as well as maintaining the sperm on the zona pellucida once the acrosome reaction has occurred. PMID- 1908771 TI - Localization of TIMP in cycling mouse hair. AB - TIMP (tissue inhibitor of metalloproteinase) is a glycoprotein inhibitor of metalloproteinases that we hypothesize to be involved in the tissue remodeling that occurs during each hair growth cycle. We examined this hypothesis by studying the expression of TIMP at selected times during a single hair cycle using TIMP-lacZ transgenic mice to localize TIMP gene activity in the hair follicle. TIMP gene induction was visualized by staining mouse back skin for beta galactosidase (beta-gal) activity. Paraffin sections were analyzed for the localization of TIMP expression. TIMP gene activation appears in hair follicles only during the mid-anagen (the growing stage of the hair cycle) primarily in Henle's layer of the inner root sheath. Some expression of TIMP is also seen in a few connective tissue cells, in the sebaceous gland and in cells at the proximity of the dermal papilla cells in catagen (regressing) and telogen (resting) follicles. These results are consistent with a role for TIMP in cyclic remodeling of connective tissue in hair follicles. PMID- 1908772 TI - Lineage of neurons and glia in chick dorsal root ganglia: analysis in vivo with a recombinant retrovirus. AB - We used retrovirus-mediated gene transfer to study the lineage of neural crest cells in chick embryos. Individual crest cells were infected before they migrated from the neural tube, and their clonal progeny were subsequently revealed in sensory ganglia and associated structures by a histochemical stain for the viral gene product (lacZ). We found that crest cells were multipotential in several respects. (1) Many clones contained both ventrolateral (VL) and dorsomedial (DM) neurons, which had been suggested to be lineally distinct. (2) Many clones contained both large and small neurons, which are known to innervate distinct targets. (3) Many clones contained multiple glial subtypes, e.g. both Schwann cells, which ensheath axons, and satellite cells, which ensheath neuronal somata. (4) Many clones contained both neurons and glial cells. On the other hand, a sizeable minority of clones was homogenous, e.g. they contained only neurons or only glial cells--suggesting that some progenitors may be, or become, restricted in potential. Finally, this study provides the first opportunity to compare directly the two methods currently available for tracing cell lineage in vertebrate embryos, retroviral infection and tracer injection: our results and those of Bronner-Fraser and Fraser (1989), who used the latter method, provide complementary but consistent views of crest lineage. PMID- 1908773 TI - Hypoxia reduces the conduction velocity of the excitation along the striated muscles in man. AB - The conduction velocity of the excitation along the striated muscles in man, hereafter refered to as muscle fiber conduction velocity (MFCV) was used to estimate the muscle functional state under hypoxaemic hypoxia. The averaged MFCV was counted by the method based on the surface measurements (using bipolar "branched" multielectrodes) of the electrically elicited compound action potentials of the brachial biceps muscle. The arterial and venous blood-gas and acid-base parameters were simultaneously measured and the body temperature was controlled intramuscularly. With afebrile patients under normoxaemia or hypoxaemia following brain stroke, MFCV decreased proportionnally to the arterial partial oxygen pressure (PaO2) rate; a strong positive correlation (r = 0.882) between MFCV and PaO2 was found up to PaO2 of 12.0 kPa and MFCV 3.5 m/s. In the case of over PaO2 = 12.0 kPa, the relationship entered into saturation; the further increase PaO2 was not followed by concomitant changes in MFCV. The results show that MFCV-testing is a valuable tool to evaluate the functional state of the striated muscle under hypoxia. PMID- 1908774 TI - Evaluation of the genotoxic potential of glutaraldehyde. AB - The cytotoxic and genotoxic effects of glutaraldehyde were studied in vitro in the human TK6 lymphoblast cell line and in primary cultures of rat hepatocytes. TK6 lymphoblasts were exposed to glutaraldehyde for 2 hr in serum-free GSH-free media. Cytotoxic effects were observed at concentrations as low as 10 microM with only 10% cell survival at 20 microM. Alkaline elution studies indicated that glutaraldehyde-induced DNA-protein crosslinking increased linearly over the concentration range from 0 to 25 microM. Glutaraldehyde-induced mutations were assessed at the thymidine kinase locus over the same concentration range and reached a plateau at 10 microM of about six times the background mutant frequency. At equivalent levels of DNA-protein crosslinks and cytolethality, glutaraldehyde was mutagenic at approximately a one-seventh lower concentration than the rodent nasal carcinogen formaldehyde (Craft et al.; Mutation Research 176:147-155, 1987). Glutaraldehyde induced a marginal increase in unscheduled DNA synthesis in the in vitro hepatocyte DNA repair assay, but only at the two highest concentrations of 50 and 100 microM, indicating the induction of some DNA excision-repair activity. These data demonstrate that glutaraldehyde exhibits DNA reactive genotoxic activity that may involve, at least in part, DNA-protein crosslinking in these cell culture models. These findings suggest the need to examine the potential carcinogenic activity of glutaraldehyde in appropriate inhalation studies. PMID- 1908775 TI - Genotoxicity studies with the unstable zeste-white (UZ) system of Drosophila melanogaster: results with ten carcinogenic compounds. AB - To increase the number of chemicals tested using the zeste-white (UZ) somatic mutation assay, ten selected carcinogens (acetamide, acrylamide, benzo(alpha)pyrene, cyclophosphamide, diethylstilbestrol, 4-nitroquinoline N oxide, propyleneimine, safrole, thiourea, and o-toluidine) have been evaluated in this assay. Our results show that all the compounds tested produce significant increases in the eye spot frequency at, at least, one of the concentrations assayed, indicating that the zeste-white assay appears to be highly sensitive to these carcinogenic compounds. That is in agreement with data previously reported by other authors. PMID- 1908776 TI - Elongation factor 2 from Artemia salina embryos and its affinity for ribosomes. AB - Crude extracts from Artemia salina undeveloped embryos do not contain detectable elongation-factor-2 (EF2) kinase and endogenous ADP-ribosylating activities. Accordingly, EF2 purified from this source is an enzyme relatively free from phosphorylated and ADP-ribosylated forms. Endogenous ADP-ribosyltransferase activity appears only after purification of EF2. The affinities of EF2 and of ADP ribosyl-EF2 for ribosomes from A. salina undeveloped embryos have been calculated by measuring the ability of the factors to inhibit the N-glycosidase activity of ricin on ribosomes. PMID- 1908777 TI - Interaction of lipoamide dehydrogenase with the dihydrolipoyl transacetylase component of the pyruvate dehydrogenase complex from Azotobacter vinelandii. AB - The interaction between lipoamide dehydrogenase (E3) and dihydrolipoyl transacetylase (E2p) from the pyruvate dehydrogenase complex was studied during the reconstitution of monomeric E3 apoenzymes from Azotobacter vinelandii and Pseudomonas fluorescens. The dimeric form of E3 is not only essential for catalysis but also for binding to the E2p core, because the apoenzymes as well as a monomeric holoenzyme from P. fluorescens, which can be stabilized as an intermediate at 0 degree C, do not bind to E2p. Lipoamide dehydrogenase from A. vinelandii contains a C-terminal extension of 15 amino acids with respect to glutathione reductase which is, in contrast to E3, presumably not part of a multienzyme complex. Furthermore, the last 10 amino acid residues of E3 are not visible in the electron density map of the crystal structure and are probably disordered. Therefore, the C-terminal tail of E3 might be an attractive candidate for a binding region. To probe this hypothesis, a set of deletions of this part was prepared by site-directed mutagenesis. Deletion of the last five amino acid residues did not result in significant changes. A further deletion of four amino acid residues resulted in a decrease of lipoamide activity to 5% of wild type, but the binding to E2p was unaffected. Therefore it is concluded that the C terminus is not directly involved in binding to the E2p core. Deletion of the last 14 amino acids produced an enzyme with a high tendency to dissociate (Kd approximately 2.5 microM). This mutant binds only weakly to E2p. The diaphorase activity was still high. This indicates, together with the decreased Km for NADH, that the structure of the monomer is not appreciably changed by the mutation. Rather the orientation of the monomers with respect to each other is changed. It can be concluded that the binding region of E3 for E2p is constituted from structural parts of both monomers and binding occurs only when dimerization is complete. PMID- 1908778 TI - Evidence for the endogenous GTP-dependent ADP-ribosylation of the alpha-subunit of the stimulatory guanyl-nucleotide-binding protein concomitant with an increase in basal adenylyl cyclase activity in chicken spleen cell membrane. AB - We investigated the endogenous GTP-dependent ADP-ribosylation of the alpha subunit of the stimulatory guanyl-nucleotide-binding protein (Gs alpha) concomitant with an increase of basal adenylyl cyclase activity in chicken spleen cell membranes. When these membranes were incubated with [adenylate-32P]NAD, there was significant incorporation of [32P]ADP-ribose into a 45-kDa acceptor protein in the membranes. This reaction was inhibited when 20 mM arginine was present during the incubation. When the membranes were incubated with unlabelled NAD, subsequent ADP ribosylation by cholera toxin was diminished significantly. Thus, chicken spleen cell membranes have the potential to endogenously ADP ribosylate the arginine residue of Gs alpha. The endogenous ADP-ribosylation Gs alpha was enhanced by the addition of 0.1 mM GTP or 0.1 mM guanosine 5'-[gamma thio]triphosphate (GTP[S]), but not 0.1 mM GDP, 0.1 mM ATP or 0.1 mM ADP. The endogenous GTP-dependent ADP-ribosylation of Gs alpha stimulated basal adenylyl cyclase activity. Furthermore, NAD-induced stimulation of basal adenylyl cyclase activity was suppressed, when the membranes were incubated with NAD in the presence of novobiocin, an inhibitor of arginine-specific ADP-ribosyltransferase. These data represent the first demonstration that a eukaryotic cell membrane contains an ADP-ribosyltransferase which can catalyze the endogenous GTP dependent ADP-ribosylation of the arginine residue of Gs alpha and that this modification enhances basal adenylyl cyclase activity in the membrane. In light of this evidence, the possible control of basal adenylyl cyclase activity via endogenous GTP-dependent ADP-ribosylation in eukaryotic cells warrants further attention. PMID- 1908779 TI - Alteration of the cytoskeleton of mammalian cells cultured in vitro by Clostridium botulinum C2 toxin and C3 ADP-ribosyltransferase. AB - The effects of Clostridium botulinum C3 ADP-ribosyltransferase and of Clostridium botulinum C2 toxin were studied on the cytoskeleton of rat hepatoma FAO and human glioma U333 cells. After treatment of these cells for 24 to 48 h with C3 (3-30 micrograms/ml), the actin microfilaments disappeared, and the intermediate filament network was found to collapse, while microtubules remained intact. Similar alterations of the cytoskeletal filaments without affecting microtubules were induced by the actin-ADP-ribosylating C2 toxin. In FAO cells, C3 caused the rounding up of cells. Concomitantly, cytosolic 22 to 24 kDa proteins were ADP ribosylated in a guanine nucleotide-dependent manner. Rounding up of cells and ADP-ribosylation of proteins in intact cells were observed at similar concentration of the transferase. These data suggest a role of the protein substrates of C3 in the regulation of the cytoskeletal integrity. PMID- 1908780 TI - Comparison of radionuclide estimation of glomerular filtration rate using technetium 99m diethylenetriaminepentaacetic acid and chromium 51 ethylenediaminetetraacetic acid. AB - Simultaneous measurements of the clearance rates of technetium 99m diethylenetriaminepentaacetic acid (99mTc-DTPA) and chronium 51 ethylenediaminetetraacetic acid (51Cr-EDTA) were performed in 30 patients with a range of renal function (glomerular filtration rates between 9 and 120 ml/min). Using multiple blood samples, the two clearance values correlated well (r = 0.991, standard error 3.9 ml/min), but DTPA clearance was systematically higher by 7.6%. For each radiopharmaceutical, an equation was derived to correct clearance values obtained using only plasma samples taken at 2 and 4 h for the systematic error inherent in this technique compared with analysis of the complete plasma concentration-time curve. The root mean square error remaining after application of these equations was 1.9 ml/min for both the EDTA and DTPA data. The corresponding errors obtained using the equation derived by Brochner Mortensen for EDTA plasma clearance were 2.2 ml/min and 1.9 ml/min, respectively, these values were not significantly different from those obtained using the equations derived in this study. PMID- 1908781 TI - Angiotensin II AT2 receptors do not interact with guanine nucleotide binding proteins. AB - We have studied the effect of GTP gamma S on the affinity and binding kinetics of angiotensin II in plasma membrane particulate prepared from tissues expressing either only AT1 (human renal artery smooth muscle cells), only AT2 (human myometrium and bovine cerebellar cortex) or both angiotensin II receptor subtypes (rat adrenal glomerulosa). We also examined the ability of angiotensin II to stimulate GTP gamma[35S] incorporation in these membrane preparations. In contrast to its effects on angiotensin II binding to the AT1 receptor, GTP gamma S does not affect binding parameters to the AT2 receptor. Moreover, in tissues expressing solely AT2 receptors, angiotensin II was unable to induce GTP gamma[35S] incorporation. These findings indicate that AT2 receptors do not interact with G-proteins and that angiotensin II must therefore mediate some of its effects through G-protein-independent mechanisms. PMID- 1908782 TI - The occurrence of Listeria species in pate: the Cardiff experience 1989. AB - Samples of 216 pates were examined for the presence of Listeria spp. between May and August 1989; 35% were contaminated with L. monocytogenes, 5% of samples having counts of greater than 10(4)/g. L. innocua was recovered from 2% of samples but no other species was isolated. Five serotypes of L. monocytogenes were represented (1/2, 4b, 4b(X), 4 not 4b or 4b(X), and NT), 4b was the predominant serotype and multiple serotypes were found in eight pates. The incidence of contamination with L. monocytogenes was greater in stored pate (46%) than display pate (30%). Sampling over a 21-day period showed an apparent increase in numbers of L. monocytogenes in 6 of 7 samples with multiple serotypes represented. There was no correlation between contamination of pate by L. monocytogenes and the presence of coliforms. Comparisons are made between the contamination of soft cheese and pate. PMID- 1908783 TI - Physical protection against airborne pathogens and pollutants by a novel animal isolator in a level 3 containment laboratory. AB - A containment laboratory unit for research with aerosols of group 2 pathogenic microorganisms is described. The design criteria are based on current UK guidelines, which imply containment at group 3 level during aerosol production, storage, exposure of animals and sampling. Within the aerosol laboratory, primary containment is provided by a Henderson apparatus operating at a negative pressure to the external environment. Flexible film isolators under negative pressure are used for all hazardous microbiological work, e.g. tissue homogenization, and for housing infected laboratory rodents. A novel feature of the animal isolator is the separate ventilation of each cage, which minimizes the risk of cross infection by aerosol transmission and ensures a similar environment within each cage. The results of an intentional release of a cloud of non-pathogenic microorganisms are presented to show the effectiveness of the containment barriers. Recommendations are given for the safe operation of a containment unit based upon practical experience. PMID- 1908784 TI - Ten and a half years seroepidemiology of Mycoplasma pneumoniae infection in Denmark. AB - The study was based on a computerized card index of 9161 patients who had at least one positive blood specimen in the Mycoplasma pneumoniae complement fixation test. A total of 12,562 specimens from these patients had been sent to Statens Seruminstitut from hospitals and general practitioners during a 10.5-year period. The period encompassed a previously described endemic period in a 30-year study of the epidemiological pattern of M. pneumoniae infection in Denmark. The serological data presented support the hypothesis advanced here that a more than sixfold increase of children in day care might have contributed to a change in the epidemiological pattern. The correlation between age and level of specific antibodies, as well as persistence of seropositivity, were also investigated. PMID- 1908785 TI - Electron microscopy of liver in patients with chronic haemodialysis. AB - Liver biopsies were performed on 18 haemodialysis patients with clinically as well as clinico-chemically altered liver values and partially positive HBV marker serology, with the view to comparing these values with ultrastructural findings in correlation with histological and immunohistological results. The following characteristic combination of findings was recorded at ultrastructural level: hypertrophy and hyperplasia of agranular endoplasmic reticulum of hepatocytes, haemosiderin deposits in Kupffer cells and hepatocytes, invasion of lymphocytes into Disse and intercellular spaces; megamitochondria in hepatocytes and perisinusoidal fibrosis established in some cases. The same findings proved to be recordable in histological diagnosis of hepatitis or toxico-metabolic liver damage. The study shows that inflammatory lesions are not all the only causes for haemodialysis-related changes in clinico-chemical values, so that liver biopsies together with ultrastructural investigations are indicated for differential diagnosis. PMID- 1908786 TI - Mast cell degranulating (MCD) peptide and its optical isomer activate GTP binding protein in rat mast cells. AB - The MCD peptide in bee venom induces degranulation in mast cells. The internal calcium concentration of mast cells increased and remained high following MCD stimulation. This calcium increase was blocked by pertussis toxin (Ptx) treatment, suggesting that MCD peptide activates Ptx-sensitive G-protein. Even in the absence of external calcium in the incubation medium, the calcium concentration increased by MCD treatment, but soon returned to the original level. D-MCD, the optical isomer of the MCD peptide, also increased the internal calcium concentration through a Ptx-sensitive pathway. We suggest that cationic clusters at one side of the surface are more important in activating the G protein than the alpha-helix conformation. PMID- 1908787 TI - Mutant analysis of interaction of the Bacillus subtilis transcription regulator AbrB with the antibiotic biosynthesis gene tycA. AB - The AbrB protein of B. subtilis represses the transcription of various postexponentially expressed genes, such as the antibiotic biosynthesis gene tycA. Recently, we have shown that ArbB binds to the tycA promoter region at two A + T rich sites; the 'promoter site' (-60 to -35) and the 'leader site' (+169 to +231). In this study we demonstrate that a Ptyc-lacZ fusion missing the leader region is constitutively expressed in wild-type B. subtilis cells and in B. subtilis cells carrying spoOA or abrB mutations. We also show that substitution mutations within the recently reported potential helix-turn-helix DNA binding motif of AbrB did not affect its specific DNA binding ability. PMID- 1908788 TI - Widespread distribution of Gq alpha/G11 alpha detected immunologically by an antipeptide antiserum directed against the predicted C-terminal decapeptide. AB - Antisera were raised to a synthetic peptide which represents the predicted C terminal decapeptide of the alpha subunit of the G-proteins Gq and G11. Competitive ELISA indicated that antiserum CQ2 displayed strong reactivity against this peptide. Antiserum CQ2 identified an apparently single polypeptide of 42 kDa which was expressed widely. The mobility of this polypeptide in SDS PAGE was not modified by pretreatment of cells with pertussis toxin, indicating that it was not a substrate for this toxin. Furthermore, the levels and mobility of this polypeptide were unaltered by treatment of cells with cholera toxin, defining that it was not related to Gs alpha. PMID- 1908789 TI - Two lipoyl domains in the dihydrolipoamide acetyltransferase chain of the pyruvate dehydrogenase multienzyme complex of Streptococcus faecalis. AB - A fragment of DNA incorporating the gene, pdhC, that encodes the dihydrolipoamide acetyltransferase (E2) chain of the pyruvate dehydrogenase multienzyme complex of Streptococcus faecalis was cloned and a DNA sequence of 2360 bp was determined. The pdhC gene (1620 bp) corresponds to an E2 chain of 539 amino acid residues, Mr 56,466, comprising two lipoyl domains, a peripheral subunit-binding domain and an acetyltransferase domain, linked together by regions of polypeptide chain rich in alanine, proline and charged amino acids. The S. faecalis E2 chain differs in the number of its lipoyl domains from the E2 chains of all bacterial pyruvate dehydrogenase complexes hitherto described. PMID- 1908790 TI - Identities of four low-molecular-mass subunits of the photosystem I complex from Anabaena variabilis ATCC 29413. Evidence for the presence of the psaI gene product in a cyanobacterial complex. AB - Photosystem I (PSI) complex of Anabaena variabilis ATCC 29413 consists of at least 11 subunits, 9 of which are resolved by high resolution gel electrophoresis. N-terminal amino acid sequences of the four subunits with molecular masses of 6.8, 5.2, 4.8 and 3.5 kDa were determined. Based on the sequence homology, the 3.5 kDa subunit was revealed to correspond to PSI-I (the gene product of psaI), which had so far been detected only in higher plant PSI complexes. The 6.8 kDa protein and 4.8 kDa protein were identified as gene products of psaK and psaJ, respectively. The 5.2 kDa protein was homologous to a 4.8 kDa subunit of PSI of the thermophilic cyanobacterium Synechococcus vulcanus, suggesting that this protein is a component of PSI in cyanobacteria. PMID- 1908791 TI - Degradation of transcription factors, c-Jun and c-Fos, by calpain. AB - c-Jun protein, and AP1/PEA1 transcription factor component, is a typical short lived protein, and like other short-lived proteins such as c-Fos, contains PEST regions. Calcium-dependent neutral protease (calpain), a candidate for the degradation of PEST-containing proteins, digests c-Jun and c-Fos efficiently in vitro. This is the first demonstration that transcription factors are substrates for calpain. The C-terminal portion of c-Jun is relatively resistant to calpain such that an 18kDa fragment, which includes the DNA binding domain, accumulates under moderate digestion conditions. The activity of c-Jun in cultured cells can be modified by changing the level of calpastatin, an endogenous calpain inhibitor, indicating that c-Jun is also a substrate for calpain in vivo. PMID- 1908793 TI - Magnetic resonance studies of murine macrophages. Proliferation is not a prerequisite for acquisition of an 'activated' high resolution spectrum. AB - Proton magnetic resonance spectroscopy (1H-MRS) was used to investigate the membranes of macrophages activated by gamma-interferon in vitro and by Listeria monocytogenes in vivo. We report the appearance with activation, of a high resolution spectrum indistinguishable from that found in activated T and B cells and embryonic and malignant cell types previously studied. We furthermore show that proliferation is not a prerequisite for the appearance of this activated spectrum. This supports the idea that membrane 'activation' in all cells, irrespective of origin, may be accompanied by similar architectural changes, and suggests that a common pathway exists for the activation of cell membranes of the immune system, possibly important in the acquisition of increased motility. The use of 1H-MRS as a non-invasive tool for analysis of activation is discussed. PMID- 1908792 TI - Two different types of channels are targets for potassium channel openers in Xenopus oocytes. AB - K+ channel openers elicit K+ currents in follicle-enclosed Xenopus oocytes. The most potent activators are the pinacidil derivatives P1075 and P1060. The rank order of potency to activate K+ currents in follicle-enclosed oocytes was: P1075 (K0.5:5 microM) greater than P1060 (K0.5:12 microM) greater than BRL38227 (lemakalim) (K0.5:77 microM) greater than RP61410 (K0.5:100 microM) greater than (-)pinacidil (K0.5:300 microM). Minoxidil sulfate, nicorandil, RP49356 and diazoxide were ineffective. Activation by the K+ channel openers could be abolished by the antidiabetic sulfonylurea glibenclamide. It was not affected by the blocker of the Ca(2+)-activated K+ channels charybdotoxin. The various K+ channel openers failed to activate glibenclamide-sensitive K+ channels in defolliculated oocytes, but BRL derivatives (K0.5 for BRL38226 is 150 microM) and RP61419 inhibited a background current. The channel responsible for this background current is K+ permeable but not fully selective for K+. It is resistant to glibenclamide. It is inhibited by Ba2+, 4-aminopyridine, Co2+, Ni2+ and La3+. PMID- 1908794 TI - Nucleotide sequence of the secY gene from Lactococcus lactis and identification of conserved regions by comparison of four SecY proteins. AB - Sec Y is an integral membrane protein which participates in the translocation of proteins through the bacterial cell membrane. We have cloned the sec Y gene of Lactococcus lactis, and found its deduced protein sequence, 439 amino acids long, to be similar in length to the previously determined Sec Y proteins of Escherichia coli, Bacillus subtilis and Mycoplasma capricolum. Comparison of the L. lactis Sec Y to the 3 other Sec Y proteins revealed 90 conserved amino acid residues (21%). Nearly half of the conserved residues are clustered in 2 of the 10 transmembrane segments, and in 2 of the 6 cytoplasmic regions. Some of the conserved regions are apparently responsible for the interactions of Sec Y with signal sequences, and the proteins SecE and SecA. PMID- 1908795 TI - Guanosine nucleotides modulate the inhibitory effect of brefeldin A on protein secretion. AB - Brefeldin A (BFA) causes rapid redistribution of Golgi proteins into the endoplasmic reticulum (ER), leaving no definable Golgi-apparatus, and blocks transport of proteins from the ER to distal secretory compartments of the cell. Using pulse-chase experiments the present study shows that BFA (1 microgram/ml) inhibits basal and CCK-stimulated protein secretion in isolated pancreatic acinar cells by 65 +/- 6% and 84 +/- 5%, respectively. In isolated permeabilized cells higher concentrations of BFA (30 micrograms/ml) were necessary to obtain inhibition of protein secretion. In parallel experiments protein secretion was stimulated by GTP (1 mM). BFA had no inhibitory effect on protein secretion in the presence of GTP, indicating that BFA might act on a GTP-binding protein. Investigating the effect of BFA on small molecular weight GTP-binding proteins we observed that [alpha-32P]GTP binding to a 21 kDa protein in a subcellular fraction enriched in ER was increased in the presence of BFA. We conclude that this 21 kDa and possibly also other GTP-binding proteins may be the molecular target of Brefeldin A in pancreatic acinar cells. PMID- 1908796 TI - A PAF-acetylhydrolase activity in Tetrahymena pyriformis cells. AB - Our study provides evidence for the existence of an acylhydrolase activity in Tetrahymena pyriformis cells, capable of hydrolyzing the sn-2 ester bond of the PAF molecule. This activity is mainly distributed in the microsomal fraction (76.5% of total) and has properties similar to the mammalian PAF-acetylhydrolase since it is Ca(2+)-independent, acid-labile, is inhibited by DFP and PMSF but it is not affected by egg yolk phosphatidylcholine. This microsomal acylhydrolase has apparent Km and Vmax values of 1.56 microM and 373 pmols.mg.min respectively. This is the first report of the existence of a PAF-acetylhydrolase activity in a non-mammalian cell. PMID- 1908798 TI - Molecular cloning, nucleotide sequence and expression of the tufB gene encoding elongation factor Tu from Thermus thermophilus HB8. AB - The tufB gene encoding elongation factor Tu (EF-Tu) of Thermus thermophilus HB8 was cloned and expressed. Compared with the known tufA gene of T. thermophilus, nucleotide differences were found at 10 positions out of 1221 nucleotides, and amino acid substitutions were found at 4 positions out of 406 amino acids. The tufB product was 70.9% homologous to the corresponding sequence of the tufB product of E. coli. The G+C content of the third base of the codon in the tufB gene was 84.8% and G was especially preferred in this position. PMID- 1908797 TI - Protein kinase C of a human megakaryoblastic leukemic cell line (MEG-01). Analysis of subspecies and activation by diacylglycerol and free fatty acids. AB - Protein kinase C (PKC) from a human megakaryoblastic leukemic cell line (MEG-01) was resolved into two fractions by hydroxyapatite column chromatography, which are indistinguishable from the brain type II (beta I/beta II) and type III (alpha) subspecies, by biochemical and immunoblot analysis. In the presence of both phosphatidylserine and diacylglycerol, several free unsaturated fatty acids (FFA's), such as arachidonic, oleic, linoleic and linolenic acids, further enhanced the enzyme activation, and allowed the enzyme to exhibit almost full activity at nearly basal levels of Ca2+ concentration. The concentration of unsaturated FFA's giving rise to the maximum enzyme activation was around 2 x 10( 5) M. Palmitic and stearic acids were inactive. The result implies that, in addition to diacylglycerol, the receptor-mediated release of unsaturated FFA's from membrane phospholipids may also take part in the activation of PKC. PMID- 1908799 TI - Subcutaneous injection or infusion of gonadotropin releasing-hormone agonist buserelin in the treatment of enlarged uteri harboring leiomyomata. AB - Thirteen women with symptomatic enlarged leiomyomatous uteri completed 6 months treatment with the gonadotropin releasing-hormone agonist (GnRH-a) buserelin, 600 micrograms daily subcutaneously (s.c.). Seven patients received injections (200 micrograms thrice daily, I-group) and six infusion by pump (50 micrograms.min (1).2 h-(1). P-group). Residual uterine volumes after 6 months therapy were comparable in both study groups (I-group median 37%, range 23 to 74%; P-group median 49%, range 30 to 69%), as were estradiol levels. Symptoms were well controlled within short time. Six months posttreatment follow-up revealed uterine regrowth to pretreatment dimensions in all but 1 patient with recurrence of symptoms in most women. During therapy, several biochemical indices of bone metabolism were significantly elevated, reflecting an increased bone resorption; they were restored within 3 months after cessation of therapy, except for alkaline phosphatase. Triglycerides and HDL-cholesterol did not change during study; cholesterol was slightly, but significantly elevated after 6 months therapy. GnRH-a buserelin, 600 micrograms daily by s.c. injection or infusion is equally effective in reducing enlarged leiomyomatous uteri. Discontinuation of therapy is followed by uterine regrowth with recurrence of symptoms in most women. The present mode of therapy seems to be beneficial as an adjunct before myomectomy, or in advancing menopause in symptomatic, climacteric women. PMID- 1908800 TI - Peanut agglutinin and chondroitin-6-sulfate are molecular markers for tissues that act as barriers to axon advance in the avian embryo. AB - Axon outgrowth between the spinal cord and the hindlimb of the chick embryo is constrained by three tissues that border axon pathways. Growth cones turn to avoid the posterior sclerotome, perinotochordal mesenchyme, and pelvic girdle precursor during normal development and after experimental manipulation. We wanted to know if these functionally similar barriers to axon advance also share a common molecular composition. Since the posterior sclerotome differentially binds peanut agglutinin (PNA) and since PNA binding is also typical of prechondrogenic differentiation, we examined the pattern of expression of PNA binding sites and cartilage proteoglycan epitopes in relation to axon outgrowth. We found that all three barrier tissues preferentially express both PNA binding sites and chondroitin-6-sulfate (C-6-S) immunoreactivity at the time when growth cones avoid these tissues. Moreover, both epitopes are expressed in the roof plate of the spinal cord and in the early limb bud, two additional putative barriers to axon advance. In contrast, neither epitope is detected in peripheral axon pathways. In the somites, this dichotomous pattern of expression clearly preceded the invasion of the anterior sclerotome by either motor growth cones or neural crest cells. However, in the limb, barrier markers disappeared from presumptive axon pathways in concert with the invasion of axons. Since this coordinate pattern suggested that the absence of barrier markers in these axon pathways requires an interaction with growth cones, we analyzed the pattern of barrier marker expression following unilateral neural tube deletions. We found that PNA-negative axon pathways developed normally even in the virtual absence of axon outgrowth. We conclude that the absence of staining with carbohydrate specific barrier markers is an independent characteristic of the cells that comprise axon pathways. These results identify two molecular markers that characterize known functional barriers to axon advance and suggest that barrier tissues may impose patterns on peripheral nerve outgrowth by virtue of their distinct molecular composition. PMID- 1908801 TI - Leukemia inhibitory factor sustains the survival of mouse primordial germ cells cultured on TM4 feeder layers. AB - Various growth factors and cytokines were tested for their effects on survival and proliferation of mouse primordial germ cells (PGCs) cultured on TM4 cell feeder layers. Leukemia inhibitory factor was able to sustain the survival of PGCs from 10.5 dpc embryos for at least 3 days and to slow down degeneration of PGCs from 11.5 dpc embryos cultured on TM4 feeder layers. PMID- 1908802 TI - FSH- and TSH-binding cells in the ovary of the developing chick embryo. AB - The numerical density (Nv) and location of thyroid stimulating hormone (TSH)- and follicle stimulating hormone (FSH)-binding cells in the left ovary of the chick embryo were determined on Days 6.5 through 19.5 of incubation. From Days 6.5 to 11.5, TSH- and FSH-positive cells were located in the medullary cords and there was no statistically significant difference in the Nv of these two cellular populations. However, beginning on Day 12.5 and continuing through Day 19.5, TSH and FSH were bound principally to cells of the cortical cords and there was a significant difference (P less than 0.05) between the Nv of TSH-positive and FSH positive cells. Results are discussed in terms of a prevalent hypothesis that throughout chick embryo development the left ovary lacks specific receptors for TSH and FSH. PMID- 1908803 TI - [Cytogenetic analysis of the chromosomal region containing the radiosensitivity genes of Drosophila. Influence of pericentromeric heterochromatin on mutagenesis in the 44-45 region of chromosome 2]. AB - Formation of radiation-induced mutations in the 44-45 region of Drosophila melanogaster chromosome 2 carrying the In(2)G50 inversion which juxtaposes the material of this region towards the centromeric heterochromatin was studied. 14 gamma-induced rearrangements in the inverted chromosome having a new breakpoint in the 44-45 region were selected. Four of them are deletions, seven are translocations and three are transpositions. 10 of these aberrations have a second breakpoint located in the heterochromatin regions of chromosomes 2 and 3. It was shown that the frequency of deletions in the region studied is tenfold higher within the inverted chromosomes as compared with the structurally normal one. Anyway, it is essentially lower than the frequency determined in analogous experiments for the other region of the chromosome. Thus, the peculiar characteristics of radiation mutagenesis in the 44-45 region, such as the prevalence of heterochromatic aberrations in the rearrangement spectrum and the relatively low deficiency frequency are still retained after inversional shift of this region to the pericentromeric heterochromatin. PMID- 1908804 TI - [Mutagenicity background monitoring of the River Don delta water]. AB - The mutagenicity of 14 samples of Don river delta water was studied by the Ames test and the technique of estimation of Drosophila dominant lethals. Experiments revealed that mutagenic pollution of Don river delta water was total at least in April--May 1989. PMID- 1908805 TI - Effects of artificial stabilizing selection on Drosophila populations subjected to directional selection for another trait. AB - Stabilizing selection for a set of morphometric wing traits was combined with directional selection for the increased expression of radius incompletus (ri) mutation of Drosophila melanogaster. Three experimental regimes were used: directional and stabilizing selection (stabilized lines); directional selection (unstabilized lines); no selection (controls). Response to selection for ri expression was similar in all selected lines but variation of this character was higher in the unstabilized lines compared to the stabilized ones. The competitive indices measured after termination of selection did not significantly differ under different treatments while fluctuating asymmetry was significantly lower in stabilized than in unstabilized lines. The possible causes of these differences are discussed. PMID- 1908806 TI - SOS induction as an in vivo assay of enzyme-DNA interactions. AB - We have constructed strains which are convenient and sensitive indicators of DNA damage and describe their use. These strains utilize an SOS::lac Z fusion constructed by Kenyon and Walker [Proc. Natl. Acad. Sci. USA 77 (1980) 2819-2823] and respond to DNA damage by producing beta-galactosidase. They can be used to characterize restriction systems and screen for restriction endonuclease mutants. Applications include the study of other enzymes involved in DNA metabolism, such as DNA methyltransferases, topoisomerases, recombinases, and DNA replication and repair enzymes. PMID- 1908807 TI - Parameters affecting plasmid stability in Bacillus subtilis. AB - For the analysis of parameters affecting plasmid stability in Bacillus subtilis, we used a pUB 110-derived shuttle plasmid containing direct and inverted nucleotide repeats (DRs and IRs). Deletions of up to 6 kb were found to occur between DRs of 7 to 16 bp. IRs as small as 43 or 58 bp were shown to stimulate the formation of these deletions in their neighbourhood. However, these structural features (DRs and IRs) per se were not responsible for plasmid instability. The unstable recombinant plasmids, but not their deletion-carrying (delta) derivatives, were found to impair the growth of the host and to accumulate high amounts of linear plasmid multimers [high mol. wt. (hmw) DNA]. We propose that the accumulation of hmw DNA may be the major reason for the selective pressure against recombinant plasmids, and the enrichment of delta plasmids. Host mutations and other parameters increasing the stability of recombinant plasmids in B. subtilis are described. PMID- 1908808 TI - Simultaneous transient expression assays of the trypanosomatid parasite Leishmania using beta-galactosidase and beta-glucuronidase as reporter enzymes. AB - We describe a transient transfection protocol for cultured Leishmania major promastigotes, utilizing Escherichia coli genes encoding beta-galactosidase and beta-glucuronidase inserted into an expression vector derived from the dihydrofolate reductase-thymidylate synthase locus. Less than 0.1 pg of either reporter enzyme can be detected with a simple fluorimetric assay, and transfection of 10 micrograms of either reporter construct yields activities at least 100-fold over background. Simultaneous introduction of both constructs showed that the activity of each reporter gene was unaffected by the presence of the other, allowing one reporter construct to serve as a control for experimental variability in test gene constructs containing the second reporter gene. These results show that it is feasible to apply transient expression assays to the identification of cis-acting elements of genes encoding nonabundant mRNAs in the genus Leishmania. PMID- 1908809 TI - Structural relationship between the vancomycin resistance protein VanH and 2 hydroxycarboxylic acid dehydrogenases. AB - Sequencing upstream from the vanA gene of enterococcal plasmid pIP816 that confers Vm resistance revealed the presence of an ORF which could code for a protein of 322 aa designated VanH. Extensive aa similarity was detected between VanH and 2-hydroxycarboxylic acid dehydrogenase. We discuss possible roles for VanH in the synthesis of a novel type of peptidoglycan precursors with lower affinity for Vm. PMID- 1908810 TI - Improved broad-host-range lac-based plasmid vectors for the isolation and characterization of protein fusions in Pseudomonas aeruginosa. AB - Several new broad-host-range vectors for the construction of protein fusions to the Escherichia coli lacZ gene have been developed. In all of the constructs, a multiple cloning site (MCS) containing unique restriction sites is located upstream of lac operon segments whose lacZ genes lack translational start signals. Some of the vectors (pPZ10, pPZ20 and pPZ30) also contain transcriptional terminators upstream of the MCS. The new vectors allow the fusion of genes to lacZ in all translational reading frames. Due to a higher copy number they allow direct screening in E. coli for weakly expressed foreign promoters. Their usefulness for gene analysis in Pseudomonas aeruginosa was demonstrated by construction and expression of a regA'::'lacZ-encoded protein fusion. PMID- 1908812 TI - Comparing apples and oranges: does cost-effectiveness analysis deal fairly with the old and young? AB - This paper considers the role patient age plays in the type of outcome analysis most germane for policymakers: cost-effectiveness analysis. The magnitude of age bias is quantified and means to modify it are described. In particular, present value analysis (discounting) is demonstrated to markedly attenuate the effect of patient age on cost-effectiveness analysis. As the discount rate gets larger, the difference in potential "life-years" between old and young gets smaller and the age bias is minimized. However, relegating a decision about the importance of patient age to a decision about the discount rate seems inappropriate. Value judgments cannot be avoided; therefore, it is best that they be explicit. PMID- 1908811 TI - Registered nurse staffing in Pennsylvania nursing homes: comparison before and after implementation of Medicare's Prospective Payment System. AB - This paper examines changes in resident acuity and registered nurse staffing in all nursing homes in Pennsylvania before and after the introduction of the Medicare Prospective Payment System (PPS) in 1983. The analysis is based on 1980, 1982, 1985, and 1987 data from the Long Term Care Facilities Survey conducted by the State Health Data Center, Pennsylvania Department of Health. Although the acuity of nursing home residents has increased significantly since the introduction of PPS, full-time registered nurse staffing has remained unchanged, and part-time registered nurse staffing has declined. This alarming trend threatens the quality of care patients receive, yet remains largely unaddressed. PMID- 1908813 TI - [Treatment of cervical intraepithelial neoplasia using the CO2 laser]. AB - The use of laser therapy in CIN, is a practical method that has revolutionized the treatment of a very common pathology, that is the cervical neoplasia in its early stages. 86 patients with different stages of cervical intraepithelial neoplasia, were studied. Patients in groups I (45 patients) y II (28 patients), were submitted to a vaporization crater of the whole transformation zone because of having the cervical canal free of lesion. In group III (13 patients), a cylinder of the cervix was done to perform histological study, whether the cervical canal was compromised or not. The cytology control results for group I were excellent; from (45 patients) who came to 3-month check-up 79.1% of the whole presented negative II. For group II (28 patients), in first pap smear two patients (7.1%) had CIN, the rest of smears were reported 66% negative II, and in the 30.6% negative I. For the group III 14.2% (5 patients) of the whole had abnormal results, the rest of the smears 73.5% of the results reported negative II. The incidence of failure for this procedure is similar to that of hysterectomy with the same therapeutic goal . PMID- 1908814 TI - [Usefulness of intraperitoneal transfusion under direct ultrasound guidance]. AB - Experience with intraperitoneal blood transfusion, using ultrasonographic guide, in 24 patients with severe isoimmunization to Rh factor, is reported. A total of 57 procedures, were done from 24 weeks of gestation. In 66.6% two or more transfusions were done in the same product. There were 71% of alive newborns and in 29% of the cases it was not possible to improve perinatal survival. The analysis of these results were correlated with antecedents: presence of hydrops, gestational age at the time of resolving pregnancy, and main disease status. The usefulness of intraperitoneal transfusion, is commented upon, and new perspectives, as intravascular transfusion in cases with severe hydrops, are considered. PMID- 1908815 TI - [Levonorgestrel releasing subcutaneous implants. 1st year's experience]. AB - This multicentric study was done in order to know the contraceptive efficacy and side effects of subdermal implants liberating levonorgestrel, in Mexican women. Results analysis, at one year, of 246 women, at four medical centers of Mexican Institute of Social Security (IMSS), showed that this contraceptive is highly efficacious, as there were no pregnancies in 2326 months of observation. The main side effects were: menstrual disorders in 34.8% of women; soreness in implantation site in 3.6%; headache in 13.4% and nausea, dizziness and vomiting in 11.6%. The most frequent causes for implant retirement were menstrual cycle alterations, and soreness at implantation site, with 7.3 and 3.5 respectively. The continuity rate at one year was 84.3, which was higher to what has been seen at the Institution with other temporal contraceptive methods, so the implants may be considered as one more alternative in family planning methods. PMID- 1908816 TI - [Effects of Y-20811, a specific thromboxane A2 synthetase inhibitor, on chemical mediator-induced bronchoconstriction in guinea pigs]. AB - We investigated the effects of Y-20811 on chemical mediator-induced bronchoconstriction and the release of chemical mediators into lung perfusion fluid during arachidonic acid (AA)-induced bronchoconstriction in guinea pigs. Y 20811 (0.01-1 mg/kg, i.v.), like acetylsalicylic acid or indomethacin, dose dependently suppressed arachidonic acid- and LTD4-induced bronchoconstriction, and it (1 mg/kg, i.v.) also inhibited PAF-induced bronchoconstriction in guinea pigs. However, at a dose of 1 mg/kg, i.v., it was inactive against the bronchoconstriction induced by histamine, serotonin and acetylcholine in guinea pigs. Y-20811 (0.3-10 mg/kg) administered orally also prevented the LTD4-induced bronchoconstriction in a dose-dependent manner. This protective effect of Y-20811 (10 mg/kg, p.o.) persisted for at least 24 hr. Y-20811 (10 mg/kg, p.o.) also inhibited antigen-induced bronchoconstriction in guinea pigs passively sensitized with anti-ovalbumin guinea pig serum and pretreated with mepyramine. In the perfused and ventilated guinea pig lungs, Y-20811 inhibited AA-induced bronchoconstriction, decreased the release of TXA2 (estimated as TXB2) and increased the release of PGE2 into the perfused lung fluid, significantly (TXB2 and PGE2 were measured by HPLC). Therefore, Y-20811 suppressed various stimulant induced bronchoconstrictions through the decrease of TXA2 production and the increase of PGE2 production. Thus, Y-20811 should prove useful as an anti asthmatic drug. PMID- 1908817 TI - Identification of mutations in two families with sporadic hemophilia A. AB - Direct sequencing of segments of the factor VIII gene in 30 hemophiliacs with sporadic disease (32+ kb of sequence in total) revealed two missense transitions: glutamate 1704 to lysine (E1704----K) in a patient with severe hemophilia A and proline 2300 to serine (P2300----S) in a patient with mild hemophilia. Both transitions are likely to be causative mutations because the amino acids affected were evolutionarily conserved. Haplotype and sequence analysis of the mother and grandparents of patient HA12 (E1704----K) indicate that the mutation arose in the grandfather who was 27 years old when his daughter was conceived. The origin of mutation in patient HA39 (P2300----S) could not be determined. As mutations that cause mild disease can be found in seemingly unrelated families, 96 unrelated hemophiliacs were screened rapidly for the P2300----S mutation with polymerase chain reaction (PCR) amplification of specific alleles (PASA). None of these patients had the mutation. PASA was also used to conveniently assess a polymorphic site in intron 7. The polymorphism is estimated to be informative in 13% of Korean females and in 23% of Western European females. PMID- 1908819 TI - Influence of cellular differentiation on ultraviolet induced DNA damage and its repair mechanisms in B. cereus. AB - Susceptibility to UV irradiation of B. cereus BIS-59 spores undergoing germination at various stages-dormant spores to vegetative cell stage and their ability to recover from radiation damage were studied. For a given dose of radiation, the number of spore photoproducts (SPP) formed in the DNA of dormant spores was about 5-times greater than that of thymine dimers (TT) formed in the DNA of vegetative cells. At intermediate stages of the germination cycle, there was a rapid decline in the UV radiation-induced SPP formed in DNA with a concomitant increase in the UV radiation-induced TT formed in DNA. Bacterial spores undergoing germination (up to 3 hr) in the low nutrient medium (0.3% yeast extract) displayed much higher resistance to UV radiation than those germinating in the rich nutrient medium, even though there was no discernible difference under the two incubation conditions in respect of the extent of germination and the time at which the outgrowth stage appeared (3 hr). This was due to the formation TT in the DNA of spores germinating in the low nutrient as compared to that of spores germinating in the rich-nutrient medium. In UV-irradiated dormant spores, SPP formed in the spore DNA did not disappear even after prolonged incubation in the non-germinating medium. However, when the UV-irradiated dormant spores were germinated in low or rich nutrient medium, a significant proportion of SPP in DNA was eliminated. The dormant spores incubated in either of the germinating media for 15 min and then UV-irradiated were capable of eliminating SPP (presumably by monomerization) even by incubation in a non-germinating medium and in the complete absence of protein synthesis (buffer holding recovery), thereby implying that spore-repair enzymes were activated in response to initial's germination. The acquisition of photo-reactivation ability appeared in spores subjected to germination only in the rich-nutrient medium at the outgrowth stage and required de novo synthesis of the required enzymes. PMID- 1908818 TI - Association between Rh and plasma iron binding (transferrin). AB - In order to establish the mechanism involved in the maintenance of the Rh polymorphism and fetomaternal compatibility relationships, we examined a sample of children from the North Area of Santiago (Chile), with respect to their growth and development patterns since 1973. This sample had shown large sib-sib segregation distortions for the Rh system. Metric variables, such as plasma protein fractions and iron, academic performance at the end of the last secondary grade and adult stature, were studied in relation to genetic markers, viz., sex, ABO, Xg, MN, Rh, haptoglobins, phosphoglucomutase, and esterase D, by means of unbalanced one way analyses of variance. Highly significant results were found for Rh phenotypes and total iron binding capacity (TIBC, transferrin). However, plasma iron did not differ significantly among Ph phenotypes. Children with the C (Rh) specificity had higher values of TIBC than non-C or c individuals (P less than 0.00001). Evolutionary considerations regarding iron transport and erythroblastosis, relationships between Rh and the transferrin receptor at the plasma membrane, and the location of the Blym-I oncogene (that shares common sequences with transferrins) close to Rh in chromosome 1 are discussed. Less significant results were found between phosphoglucomutase and stature, gamma globulin level and sex, and academic performance (history) and sex. PMID- 1908820 TI - Effects of in vitro hyperthermia on the proliferative response of blood mononuclear cell subsets, and detection of interleukins 1 and 6, tumour necrosis factor-alpha and interferon-gamma. AB - The role of endogenously mediated fever and exogenous hyperthermia as modulators of immune functions remains poorly understood. It is known that fever is mediated by several cytokines, including interleukin-1 alpha and interleukin-1 beta (IL-1 alpha and IL-1 beta), interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF alpha) and the interferons. The present communication examines the effect of exogenous hyperthermia on the detection of these cytokines and shows the suppressive effect of elevated temperature (39 degrees) on the amount of IL-1 beta, IL-6 and IFN-gamma (P less than 0.001) but not on IL-1 alpha and TNF-alpha concentrations. It is suggested that a negative feedback mechanism exists between temperature and the production of some of the molecules involved in the mediation of fever. It is known that hyperthermia increases the proliferative response of lymphocytes. We found a twofold increase in [3H]thymidine incorporation at 39 degrees compared to 37 degrees. The distribution of cells expressing CD3, CD4, CD8, CD14, CD16, CD19 and CD25 markers was the same at 37 degrees and 39 degrees. PMID- 1908822 TI - Induction of anti-progesterone immunity and pregnancy blocking by anti progesterone anti-idiotypes. Variable efficacy of polyclonal Ab2 antibodies directed against a panel of closely related Ab1 antibodies. AB - Polyclonal rabbit anti-idiotypes (Ab2) have been raised against three mouse monoclonal antiprogesterone Ab1 antibodies (DB3, 11/32, 11/64) closely related in VH and VL sequences. The anti-idiotypes were characterized for specificity and used to immunize groups of female mice. The latter responded with production of anti-progesterone (Ab3) antibodies, confirming the ability of anti-idiotypes to mimic the immunogenicity of a steroid. The response to one of the anti-idiotypic reagents (anti-DB3-id) was 5-10 times stronger than those to the others, despite close sequence homology between the idiotypes. Moreover, immunization with anti DB3-id led to a reduction in fertility rate from 90% (control) to 30%, whereas immunization with the other anti-idiotypes was without effect. Sequence and structural comparisons suggest that residues associated with VH CDR3 and VL CDR3 may have a key role in determining the efficiency of anti-idiotypic immunization against progesterone. The variability in outcome of using anti-idiotypic reagents against a defined panel of related antibodies is relevant to the use of anti idiotypes as surrogate antigens. PMID- 1908821 TI - Patterns of cytokine production and proliferation by T lymphocytes differ in mice vaccinated or infected with Schistosoma mansoni. AB - C57BL/6 mice vaccinated with irradiated cercariae of Schistosoma mansoni are highly resistant to challenge infection. To examine the role of T-helper (Th) activity in these vaccinated (V20) mice, cells from skin- and lung-draining lymph nodes (LN) and the spleen were cultured in vitro with soluble schistosomular antigen. Peak proliferation and release of T-cell growth factor (TCGF) by axillary LN cells on Day 5, and by mediastinal LN cells on Day 18, reflected the kinetics of parasite migration. High levels of interferon-gamma (IFN-gamma) were detected and production was prolonged, particularly in the mediastinal LN. The majority of the above activity was ablated with anti-CD4 antibody. IFN-gamma production by spleen cells increased, whilst proliferation and TCGF release remained low. Although levels of proliferation were similar, more IFN-gamma was released by LN cells from V20 mice than by those from mice infected with normal parasites (NI). This difference in IFN-gamma production was magnified by the greater number of cells in LN of V20 than NI mice. On Day 22 post-exposure, 24 fold more IFN-gamma was produced per pair of axillary LN in the former group. LN cells from V20 mice produced interleukin (IL)-2 and IL-4, whereas those from NI mice released IL-2 but negligible IL-4. Greater quantities of IL-3 were secreted by cells from V20 than from NI mice. These results support the conclusion that IFN-gamma-producing memory Th cells, generated in the LN of V20 mice, play an important role in protective immunity against S. mansoni. PMID- 1908823 TI - A light & electron microscopic study on apoptotic bodies in acute aflatoxin B1 induced injury in the rat liver. AB - A subnecrogenic dose of aflatoxin B1 (AFB1) was injected intraperitoneally into 8 10 wk old male rats of the Holzman strain. Cytoplasmic and sinusoidal eosinophilic bodies were seen in the liver which appeared at 30 h and reached a maximum at 48 h. Electron microscopically some of the cytoplasmic structures were seen to be of mitochondrial origin whereas others resembled apoptotic bodies. The sinusoidal bodies were similar to apoptotic bodies. PMID- 1908824 TI - Effects of activated macrophages on Mycobacterium leprae. AB - Five alternative methods were used to explore in vitro the effects of normal and activated murine macrophages on the metabolic well-being of intracellular Mycobacterium leprae: fluorescein diacetate-ethidium bromide staining, ATP content, synthesis of phenolic glycolipid 1, and two techniques to quantitate oxidation of palmitic acid. In relatively short-term experiments (7 to 10 days), each of these procedures provided strong evidence that activated macrophages exerted a deleterious effect on the leprosy bacillus. These findings appear to confirm the contention that activated macrophages underlie host resistance to clinical leprosy and limitation of M. leprae growth in paucibacillary leprosy. PMID- 1908825 TI - Effect of site-directed mutagenic alterations on ADP-ribosyltransferase activity of the A subunit of Escherichia coli heat-labile enterotoxin. AB - Previous studies of the S1 subunit of pertussis toxin, an NAD(+)-dependent ADP ribosyltransferase, suggested that a small amino-terminal region of amino acid sequence similarity to the active fragments of both cholera toxin and Escherichia coli heat-labile enterotoxin represents a region containing critical active-site residues that might be involved in the binding of the substrate NAD+. Other studies of two other bacterial toxins possessing ADP-ribosyltransferase activity, diphtheria toxin and Pseudomonas exotoxin A, have revealed the presence of essential glutamic acid residues vicinal to the active site. To help determine the relevance of these observations to activities of the enterotoxins, the A subunit gene of the E. coli heat-labile enterotoxin was subjected to site specific mutagenesis in the region encoding the amino-terminal region of similarity to the S1 subunit of pertussis toxin delineated by residues 6 through 17 and at two glutamic acid residues, 110 and 112, that are conserved in the active domains of all of the heat-labile enterotoxin variants and in cholera toxin. Mutant proteins in which arginine 7 was either deleted or replaced with lysine exhibited undetectable levels of ADP-ribosyltransferase activity. However, limited trypsinolysis of the arginine 7 mutants yielded fragmentation kinetics that were different from that yielded by the wild-type recombinant subunit or the authentic A subunit. In contrast, mutant proteins in which glutamic acid residues at either position 110 or 112 were replaced with aspartic acid responded like the wild-type subunit upon limited trypsinolysis, while exhibiting severely depressed, but detectable, ADP-ribosyltransferase activity. The latter results may indicate that either glutamic acid 110 or glutamic acid 112 of the A subunit of heat-labile enterotoxin is analogous to those active-site glutamic acids identified in several other ADP-ribosylating toxins. PMID- 1908826 TI - Immunization with Trypanosoma cruzi epimastigote antigens incorporated into iscoms protects against lethal challenge in mice. AB - An immunoglobulin G3 monoclonal antibody obtained by immunizing mice with a cell membrane preparation of epimastigotes of Trypanosoma cruzi was shown to agglutinate live epimastigotes, lyse blood-form trypanosomes, and partially protect mice by passive transfer. The main antigens recognized by the monoclonal antibody were located in the flagella of epimastigotes and blood-form trypanosomes. Antigens of epimastigotes, purified by affinity chromatography with the monoclonal antibody, were shown to be highly glycosylated and revealed a wide band with an Mr between 45,000 and 68,000 in sodium dodecyl sulfate polyacrylamide gel electrophoresis and immunoblotting. Immunization of mice with a small concentration of the affinity purified antigens incorporated into an antigen delivery system prepared with Quil A (Isotec AB, Lulea, Sweden), a saponin derivative, induced strong antibody and cell-mediated immune responses and protected 100% of the immunized animals against death due to challenge with 100 100% lethal doses of blood form trypanosomes. Protection was due to the use of the antigen delivery system, since mice immunized with equal concentrations of antigens alone or in combination with saponin had 100% mortality. The results suggest that small concentrations of epimastigote antigens obtained by biochemical methods and incorporated into the proper antigen delivery system may serve as a vaccine against Chagas' disease. PMID- 1908827 TI - Swine immunity to an attenuated Salmonella typhimurium mutant containing a recombinant plasmid which codes for production of a 31-kilodalton protein of Brucella abortus. AB - Salmonella typhimurium chi 4064, an attenuated delta cya delta crp mutant of S. typhimurium SR-11, was shown to be avirulent in swine. S. typhimurium chi 4064 was used as a carrier for plasmid pBA31-R7, which codes for the expression of a 31-kDa protein from Brucella abortus (BCSP31). Given orally, S. typhimurium chi 4064(pBA31-R7) colonized the intestine and mesenteric lymph nodes of 5- to 6-week old crossbred swine. Orally immunized animals developed serum and intestinal antibody responses to the B. abortus 31-kDa protein and to salmonella endotoxin as measured by enzyme-linked immunosorbent assay. Similarly immunized swine did not develop delayed-type hypersensitivity following a subcutaneous injection of recombinant BCSP31. However, swine parenterally immunized with recombinant BCSP31 incorporated in Freund incomplete adjuvant did develop a delayed-type hypersensitivity response to the homologous antigen. The data indicated that oral presentation of antigen to swine in the context of recombinant S. typhimurium effective stimulated mucosal and systemic antibody-mediated immunity but failed to sensitize swine for either an antigen-specific delayed-type hypersensitivity or a blastogenic response to the cloned BCSP31. PMID- 1908829 TI - Mechanisms involved in mycobacterial growth inhibition by gamma interferon activated bone marrow macrophages: role of reactive nitrogen intermediates. AB - Murine bone marrow-derived macrophages are able to inhibit the growth of Mycobacterium bovis after stimulation with recombinant gamma interferon. This antimycobacterial activity was inhibited by NG-monomethyl-L-arginine, a specific inhibitor of nitrite and nitrate synthesis from L-arginine. Furthermore, there was a complete lack of mycobacterial growth inhibition in a medium deficient in L arginine. Nitrite is generated by gamma interferon-activated bone marrow-derived macrophages after infection with M. bovis, and a correlation between mycobacterial growth inhibition and nitrite production was observed. These results indicate that reactive nitrogen intermediates derived from L-arginine are crucially involved in macrophage antimycobacterial activity. PMID- 1908830 TI - Identification of larval cross-reactive and egg-specific antigens involved in granuloma formation in murine schistosomiasis mansoni. AB - Cross-reactive humoral immune responses between antigens of different developmental stages of the worm Schistosoma mansoni have previously been demonstrated. In contrast, information on antigenic cross-reactivity at the T cell level is still very sparse. The present study examined the cross-reactive T cell responses to eggs and crude and fractionated soluble egg antigens (SEA) in infected mice prior to (from 0 to 4 weeks of infection) and after (5 weeks and onwards) egg deposition. Splenic lymphocyte proliferation to unfractionated SEA was detected as early as 2 weeks postinfection and increased rapidly by 4 weeks postinfection. Injections of live eggs into the lungs of infected mice at 4 weeks postinfection demonstrated enhanced granuloma formation, indicating the presence of primed T cells that respond to egg antigens. Further experiments with the artificial granuloma model and polyacrylamide gel electrophoresis-separated SEA fractions demonstrated that in mice infected for 4 weeks the 60- to 66-, 93- to 125-, and greater than 200-kDa SEA fraction-coated beads elicited significant pulmonary granulomas. By 6 weeks postinfection, when eggs are deposited in the livers, in addition to the cross-reactive fractions (60 to 66, 93 to 125, and greater than 200 kDa), beads coated with fractions of 25 to 30, 32 to 38, and 70 to 90 kDa also elicited significant granulomatous reactions. These antigenic fractions are considered to have elicited egg stage-specific T-cell responsiveness. In addition hepatic granuloma T cells from the 6th week of infection demonstrated the strongest blastogenic response to the 60- to 66-kDa cross-reactive fraction. Thus, in vitro and in vivo experiments demonstrated T cell cross-reactivity between the larval and egg stages of the worm. On the basis of these observations, the appearance of the primary circumovum granulomatous response in infected mice is considered to represent the sum of larval cross reactive and egg-specific T-cell responsiveness. PMID- 1908828 TI - Staphylococcal exotoxins stimulate nitric oxide-dependent murine macrophage tumoricidal activity. AB - The staphylococcal exotoxins toxic shock syndrome toxin 1 (TSST-1) and enterotoxin B were tested for their ability to stimulate murine peritoneal macrophages (PM) for tumoricidal activity. Both toxins were found to stimulate oil-elicited, gamma interferon-primed PM monolayers to kill nonadherent P815 tumor targets. The mechanism of killing of toxin-stimulated tumoricidal activity involved the production of nitric oxide, as nitrite could be demonstrated in culture fluids, and NG-monomethyl-L-arginine, an inhibitor of nitric oxide production, abrogated toxin-stimulated tumoricidal activity. TSST-1 stimulated the secretion of tumor necrosis factor by PM monolayers in the presence and absence of gamma interferon. The mechanism of toxin-stimulated tumoricidal activity was also determined to be independent of the production of reactive oxygen intermediates in that TSST-1 failed to stimulate H2O2 production by PM. These results demonstrate that the staphylococcal exotoxins are capable of stimulating macrophage production of nitric oxide for tumor cytotoxicity and suggest that the nitric oxide thus produced may subsequently play a role in the pathogenesis of the diseases caused by these toxins. PMID- 1908832 TI - Functional evidence that the Ser-195 residue of staphylococcal exfoliative toxin A is essential for biological activity. AB - The substitution of the serine 195 residue of staphylococcal exfoliative toxin A by a cysteine residue led to a biologically inactive protein. This result is consistent with the hypothesis that exfoliative toxin A could be a protease or a lipase. However, no protease or lipase activity was detected with the native toxin. PMID- 1908831 TI - Role of beta interferon in resistance to Toxoplasma gondii infection. AB - The role of recombinant murine beta interferon (rMuIFN-beta) and recombinant human IFN-beta (rHuIFN-beta) in resistance to Toxoplasma gondii was examined. rMuIFN-beta protected mice against a lethal infection with the parasite. The protective effect appeared to depend on the concomitant release of gamma interferon. rMuIFN-beta did not activate murine peritoneal macrophages to inhibit or kill T. gondii whether used alone or in combination with lipopolysaccharide (LPS). rHuIFN-beta did not activate human monocyte-derived macrophages to inhibit or kill T. gondii when 5-day-old monocyte-derived macrophages were used. In contrast, significant killing of T. gondii was noted when 10-day-old monocyte derived macrophages were used. The addition of LPS enhanced this effect. These results revealed a role for IFN-beta in the mechanisms of defense against T. gondii and suggest its potential use in the treatment of toxoplasmosis in humans. PMID- 1908833 TI - Comparative immunochemistry of lipopolysaccharides from Branhamella catarrhalis strains. AB - Lipopolysaccharides (LPS) were extracted and purified from the type strain and from a clinical isolate of Branhamella catarrhalis. Chemical analysis revealed the presence of glucose, galactose, and glucosamine in different molar proportions in the LPS from these two isolates, whereas there was no difference between the two isolates in the ratios of ketodeoxyoctonate, phosphate, and the fatty acids C12, 3-OH-C12, and 3-OH-C11 present. Heptose or 3-OH-C14 was not detectable in either preparation. LPS from both strains appeared semirough according to sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis, presenting a core polysaccharide plus one repeating unit. Immunoblotting, passive hemolysis, and hemolysis inhibition assays using anti-LPS antibodies from immunized rabbits demonstrated cross-reactivity between the LPS preparations; however, antigenic dissimilarities were also found, suggesting that more than one serotype may exist. The lipid A isolated from the two LPS was serologically identical and exhibited cross-reactivity with lipid A of members of the family Enterobacteriaceae. The B. catarrhalis LPS were biologically active, causing lethality in D-galactosamine-sensitized C57/BL6 mice and inducing Limulus amoebocyte lysate gelation. PMID- 1908834 TI - Studies on the pathogenicity of Listeria monocytogenes. AB - The characterization of mutants of Listeria monocytogenes with reduced virulence properties is described. Reduction in the amount of the extracellular protein p60 (encoded by the ipa gene) leads to cell filaments with impaired invasiveness. Mutants which cannot synthesize listeriolysin are still invasive but unable to survive within phagocytic cells. One type of listeriolysin-negative mutants is defective in the synthesis of a positive regulatory element PrfA which coordinately regulates the listeriolysin gene (lisA) together with several other genes, including those for a phosphatidylinositol-specific phospholipase and a metalloprotease. PMID- 1908835 TI - Effect of various antibiotics on Listeria monocytogenes multiplying in L 929 cells. AB - Various antibiotics were evaluated as to their effect on Listeria monocytogenes SLCC 4013 multiplying within L 929 mouse fibroblast cells. Antibiotics were employed in concentrations above the MIC value. However, there was no measurable effect of some drugs on intracellular listeriae (azlocillin, mezlocillin, cephalothin, ciprofloxacin, chloramphenicol). With other drugs an inhibition of intracellular growth was observed (penicillin, ampicillin, rifampicin, rifapentine, erythromycin, doxycycline, co-trimoxazole, coumermycin). Notably, with none of the antibiotics a complete eradication of the listeriae was achieved. There is a good correlation of these results with animal experiments. Therefore, the cell culture system might be useful for the screening of new antibiotics. PMID- 1908836 TI - Suppressive effect of a mouse testicular extract on lymphocyte activation. AB - The effect of mouse testicular extract (TE) on lymphocyte activation was investigated. TE, in the dose range 75-600 micrograms ml-1, suppressed significantly the blastogenic response of splenocytes to concanavalin A (Con-A), pokeweed mitogen (PWM), phytohaemagglutinin (PHA) and lipopolysaccharide (LPS). TE also suppressed the blastogenic response of B-cells to LPS and of T-cells to PHA in a dose-dependent manner as well as suppressing the mixed lymphocyte reaction (MLR). Pretreatment of splenocytes with TE did not however, completely suppress their blastogenic response to Con-A, when the treated cells were washed prior to culturing. Furthermore, TE did not inhibit the on-going blastogenesis of splenocytes that had been activated already with Con-A for 48 h. Splenocytes obtained from TE-treated mice remained capable of responding to Con-A stimulation, whereas they did not respond to listerial antigens when mice were immunized with Listeria monocytogenes together with TE. The effects of TE were enhanced significantly by heating to 100 degrees C, but were resistant to pronase, RNase and DNase. These results suggest that TE affects non-specifically the stage of lymphocyte sensitization to antigens or mitogens. PMID- 1908837 TI - Pertussis toxin-induced mitogenesis in human T lymphocytes. AB - Pertussis toxin (PT) has previously been shown to affect a wide variety of immune responses and to cause lymphocyte proliferation. We have investigated the biochemical basis for the mitogenic activity of PT by using human peripheral blood lymphocytes. PT was found to induce a rapid rise in cytosolic free calcium concentration and an alkalinization of the cytosol through the Na+/H+ antiporter. The toxin was also found to induce expression of IL-2-receptor on CD3+ cells and to stimulate IL-2 production. PT induced proliferation of both CD4+ and CD8+ T cells in the presence (but not in the absence) of accessory cells. PT also stimulated IL-1 production by monocytes but neither IL-1, IL-6 alone nor a combination of the two lymphokines could replace accessory cells suggesting that cell:cell contact is required. Low doses of PT induced ADP-ribosylation of G proteins but this treatment did not affect significantly PHA-induced [Ca2+]i increase and IL-2-induced DNA synthesis suggesting that the substrates of the ADP ribosyltransferase activity of PT are not involved in the signalling pathways leading to DNA replication. PMID- 1908838 TI - Soft selection and quantitative genetic variation: a laboratory experiment. AB - The effect of environmental heterogeneity on the genetic variation of different quantitative characters was studied in two laboratory and two recently captured populations of Drosophila melanogaster. Two different culture media (habitats R and G) were used. Coarse-grained heterogeneity with independent density control in each habitat (R + G), and fine-grained (R/G) heterogeneity were simulated in population cages. Control populations in both R and G habitats were also maintained. Genetic differences for oviposition-site preference, larval preference and/or within-habitat viability were found between subpopulations sampled from different media. This happened in all four populations maintained on R + G, two populations maintained on R/G, and one control population. Thus, environmental heterogeneity seems to protect genetic variability responsible for between-habitat genetic differentiation, particularly when such heterogeneity corresponds to the 'soft selection' model (R + G). However, for the quasi-neutral trait sternopleural bristle number, no genetic between-habitat differentiation, nor increased heritability were observed in populations maintained under any kind of environmental heterogeneity. Hence, although soft selection seems to be a real force in determining adaptation to heterogeneous environments, the genetic variability maintained may be small in relation to the whole genome. PMID- 1908839 TI - The competition diallel and the exploitation and interference components of larval competition in Drosophila melanogaster. AB - A logistic model of the competition diallel is presented based on two linear parameters for the exploitation component of competition, namely the acquisition rate (f) and utilization efficiency (u), and one linear parameter for the interference component of competition (i). This interference component encompasses all phenomena that are uniquely related to duocultures, such as resource partitioning, mutual stimulation, inhibition and complementation. The model uses yield-density regression coefficients (c-values), but could be adapted to suit other variates that account for both competitor density and relative frequency. In Drosophila larval competition most interference is negative and depresses the performance of duocultures with respect to monocultures, over and above that expected from shared exploitation of a common resource. Even in the closely controlled competitive conditions of these experiments this interference accounts for a considerable proportion of the total variation. The isolation of a general, and therefore predictable, interference component may prove useful in agriculture when assessing the relative importance of mixture effects to the yield potential of different crops. PMID- 1908840 TI - Human HLA-DQ beta chain presents minor lymphocyte stimulating locus gene products and clonally deletes TCR V beta 6+, V beta 8.1+ T cells in single transgenic mice. AB - Minor lymphocyte stimulating locus (Mls) gene products in association with mouse major histocompatibility complex (MHC) class II molecules are known to determine the repertoire of T-cell receptor (TCR) in mature T cells. In order to test whether human class II molecules can present mouse Mls, HLA-DQ beta transgenic mice were generated. The expression and function of the DQ beta transgene were studied in the progeny of one selected founder which was H-2f and H-2E negative. In these mice, DQ beta molecules pairing with mouse A alpha chain and invariant chain are expressed on the cell surface in a tissue-specific manner. When the DQ beta gene was bred into the Mls-1a strain DBA/1 (H-2q), T cells bearing V beta 6 and V beta 8.1 TCR were clonally deleted in the thymus of DQ beta+ transgenics but not in DQ beta-negative full sibs. Thus, the data presented here clearly demonstrate that the human MHC DQ beta chain can present Mls in the clonal deletion of T cells. Our results also suggest the requirement for an interaction between CD4 and class II molecules (alpha chain) for clonal deletion of T cells to occur. PMID- 1908841 TI - HLA class II induction by interferon-gamma in K562 variant cell line: inhibition by serum lipid. AB - The induction of class II antigen (Ag) by interferon-gamma (IFN-gamma) in variants of the K562 cell line has been examined in this study. Following incubation of K562A cells with IFN-gamma, surface expression of HLA-DR molecules was demonstrated by indirect immunofluorescence, confirmed by immunoblotting, and HLA-DR3 Ag specificity identified. HLA-DP and HLA-DRW52 Ag were co-expressed, but no HLA-DQ expression occurred. A variant of this line, designated K1A, spontaneously developed resistance to IFN-gamma induction of class II Ag, but continued to express class I Ag. In a third K562 variant, designated K562B, no class II gene products could be induced. Northern blot analysis indicated that mRNA levels correlated with surface class I and II Ag expression in all of the K562 cell lines. Resistance to IFN-gamma inducible class II Ag expression in K1A cells did not involve changes in IFN-gamma receptor affinity or number but was shown to be due to an inhibitory effect of serum lipid. These results indicate that cells derived from a common parental line may differ in susceptibility to a regulatory mechanism affecting IFN-gamma inducible class II Ag expression. PMID- 1908842 TI - Inhibition of the action of a stimulatory GDP/GTP exchange protein for smg p21 by acidic membrane phospholipids. AB - A stimulatory GDP/GTP exchange protein for smg p21 (smg p21 GDS) stimulated the dissociation of GDP from smg p21B. This reaction was inhibited by acidic membrane phospholipids such as phosphatidylinositol, phosphatidylinositol-4-monophosphate, phosphatidylinositol-4,5-bisphosphate, phosphatidic acid, and phosphatidylserine but not by phosphatidylcholine or phosphatidylethanolamine. These acidic phospholipids inhibited the smg p21 GDS action in a manner competitive with both smg p21 GDS and smg p21B. smg p21 GDS has other actions to inhibit the binding of smg p21B to membranes and to induce the dissociation of prebound smg p21B from the membranes. The acidic phospholipids also inhibited these two actions of smg p21 GDS. smg p21B has a polybasic region and an isoprenoid moiety in its C terminal region which are necessary for its membrane-binding activity and its sensitivity to the smg p21 GDS actions. Therefore, it is possible that acidic membrane phospholipids interact with this polybasic region and thereby inhibit the smg p21 GDS actions. PMID- 1908843 TI - Second primary cancer after diagnosis of stomach cancer in Osaka, Japan. AB - The risk of developing a second primary cancer following stomach cancer was estimated from data accumulated in the Osaka Cancer Registry. Of the 38,777 male patients and 22,391 female patients newly diagnosed in the period 1966-1986 who were followed up until the end of 1986, 778 and 267 developed a second cancer other than stomach cancer, respectively, whereas the expected numbers had been 928.8 (RR = 0.84, 95% CI = 0.78-0.90) and 297.7 (RR = 0.90, 95% CI = 0.79-1.01). The risks were higher among younger patients (aged 30-54 at the diagnosis of stomach cancer) than among older patients (aged 55-69 at the diagnosis of stomach cancer). Significantly elevated risks were observed for cancers of the oral cavity & pharynx (RR = 1.56), colon (RR = 1.61) and rectum (RR = 1.56) for males, and oral cavity & pharynx (RR = 2.59) for females as second cancers. Results were substantially similar among the localized stomach cancer patients. Among younger male patients with gastrectomy, the risk of developing pancreatic cancer was elevated 10 or more years after stomach cancer diagnosis. The present study suggests the necessity of following up stomach cancer patients in order to enable the early diagnosis of digestive tract cancer. PMID- 1908844 TI - Pendolmycin, a new tumor promoter of the teleocidin A class on skin of CD-1 mice. AB - Pendolmycin, isolated from Nocardiopsis, is a compound structurally similar to teleocidin A, one of the 12-O-tetradecanoylphorbol-13-acetate (TPA)-type tumor promoters. Pendolmycin has a C5 dimethyl allyl group attached to C-7 of (-) indolactam-V, whereas teleocidin A has a C10 linalyl group attached to the molecule. The structure-activity relationships of a hydrophobic moiety attached to (-)-indolactam-V were studied in four compounds, (-)-indolactam-V, pendolmycin, teleocidin A and newly synthesized 7-(nerolidyl)-(-)-indolactam-V in tests on inhibition of the specific [3H]TPA binding to a particulate fraction of mouse skin, activation of protein kinase C and induction of both adhesion of HL 60 cells and ornithine decarboxylase in mouse skin. The potencies of the compounds for these activities increased mainly depending on the length of the hydrophobic group. Pendolmycin had a tumor-promoting activity on mouse skin initiated with a single application of 7,12-dimethyl-benz[a]anthracene, and its potency was just between those of (-)-indolactam-V and teleocidin A. The role of the hydrophobic moiety is discussed with particular emphasis on the results obtained with 7-(nerolidyl)-(-)-indolactam-V. PMID- 1908845 TI - Organ-specific modification of tumor development by low-dose combinations of agents in a rat wide-spectrum carcinogenesis model. AB - The combined effects of low doses of various carcinogens and carcinogenesis modifiers on tumor development were investigated by using a wide-spectrum organ carcinogenesis model in F344 rats. These agents were administered as three groups: (1) a group of known hepatocarcinogens; (2) a group of nitroso compounds having various target organ specificities; and (3) a group of antioxidants having various inhibiting or enhancing activities depending on the target organ. Doses were used which were generally below the known effective level for the individual chemical. These groups of chemicals were administered with or without prior administration of N-diethylnitrosamine (100 mg/kg body wt., i.p.), N methylnitrosourea (4 x 20 mg/kg body wt., i.p.) and dihydroxy-di-N propylnitrosamine (0.1% in drinking water for 2 weeks). The hepatocarcinogen group in combination with various nitroso compounds increased the incidences of liver hyperplastic nodules and hepatocellular carcinomas. In contrast, incidences were clearly reduced when the hepatocarcinogens and/or the nitroso compounds were administered in combination with the antioxidants. For the urinary bladder, the combination with nitroso compounds and antioxidants enhanced cancer development, and the addition of hepatocarcinogens further increased tumorigenesis. For the glandular stomach, additive effects on the numbers of pepsinogen isozyme 1 altered pyloric glands, a putative preneoplastic lesion, were produced by the combination treatment of antioxidants and the nitroso compounds. No synergistic effects on tumor development were seen in other organs. The results of the present study demonstrated that combinations of various compounds at low doses can additively or synergistically exert either enhancing or inhibitory effects on the development of preneoplastic and neoplastic lesions in different organs in a single model having a wide spectrum of organ effects. PMID- 1908846 TI - Effects of 3-aminobenzamide on induction of multiorgan carcinogenesis by N nitrosobis(2-hydroxypropyl)amine in hamsters. AB - The effects of an inhibitor of poly(ADP-ribose)polymerase, 3-aminobenzamide (ABA), on N-nitrosobis(2-hydroxypropyl)amine (BHP)-induced pancreas, liver, gallbladder and lung carcinogenesis in Syrian golden hamsters were investigated. Animals were given either BHP alone, by subcutaneous injection at a dose of 500 mg/kg body weight, or in combination with an intraperitoneal injection of ABA 30 min after the BHP at a dose of 300 or 600 mg/kg body weight once a week for 5 weeks, and then killed 35 weeks after the commencement of the experiment. ABA exerted inhibitory effects on pancreas and lung carcinogenesis induced by BHP, with mean numbers of lesions (including hyperplasias and carcinomas) being significantly decreased compared with the BHP-alone group values, while no significant effect was observed on liver or gallbladder carcinogenesis. These results suggest that the effects of ABA on carcinogenesis depend on the target organ as well as the chemical carcinogen examined. PMID- 1908847 TI - Changes in carboxylesterase isoenzymes of rat liver microsomes during hepatocarcinogenesis. AB - Among the three major carboxylesterase isoenzymes, RH1, RL1 and RL2, present in microsomes from normal rat liver, RL2 shows hydrolyzing activity towards 12-O tetradecanoylphorbol-13-acetate and 1-oleoy1-2-acetyl-rac-glycerol, both activators of protein kinase C. Since protein kinase C has been suggested to be involved in carcinogenesis and cell proliferation, alterations in hepatic microsomal carboxylesterase isoenzymes including RL2 were studied during hepatocarcinogenesis induced by the Solt-Farber model. Alteration of RL2 was determined by measuring acetanilide-hydrolyzing activity, by quantifying the protein amount using the single radial immunodiffusion method, and by activity staining following electrophoresis of liver microsomes. The isoenzyme composition of hepatic microsomal carboxylesterase was changed after partial hepatectomy, and marked decreases in RL2 activity and protein content were observed at 4 weeks, at the time of preneoplastic foci induction. Partial hepatectomy alone also resulted in decreased RL2 activity. These findings suggest that RL2 may be involved in regulation of protein kinase C activity by metabolizing its activators at an early stage of hepatocarcinogenesis in rats. PMID- 1908848 TI - Induction of glutathione S-transferase P-form in primary cultured rat hepatocytes by epidermal growth factor and insulin. AB - The effects of epidermal growth factor (EGF) (10 ng/ml) and insulin (100 nM) on the expression of glutathione S-transferases (GSTs), especially the GST-P form (GST 7-7), were examined in primary cultured rat hepatocytes in serum-free medium. On culture with EGF and insulin, the GST activities towards 1-chloro-2,4 dinitrobenzene and 1,2-dichloro-4-nitrobenzene were transiently decreased on day 2 to 10% of those of freshly isolated hepatocytes and then increased to 60 to 100% of those of freshly isolated cells on day 4. Western blot analysis of GSTs revealed that GST-P, which is not present in freshly isolated hepatocytes, was markedly induced and that GST subunits 3 and 4 of the Mu class also increased after addition of EGF and/or insulin, while the subunits 1 and 2 of the Alpha class disappeared. Northern blot analysis showed that on addition of EGF and insulin the level of GST-P mRNA was also elevated and expressions of the nuclear oncogenes c-jun and c-fos were enhanced. These results suggest that the enhanced expression of GST-P induced by EGF or insulin in primary cultured rat hepatocytes might be regulated by JUN and FOS proteins. PMID- 1908849 TI - Stimulatory effects of retinoic acid on tumor growth and serum insulin-like growth factor-1 in rats bearing estrogen-responsive pituitary tumor MtT/Se. AB - MtT/Se is one of 4 cell lines derived from an estrogen-dependent pituitary tumor, MtT/F84. The main difference between these tumor types is that MtT/F84 secretes both growth hormone (GH) and prolactin (PRL) whereas MtT/Se secretes only GH. MtT/Se grew slowly in ovariectomized (ovex) rats, but tumor growth was much faster in estrogen-treated ovex rats. Effects of dietary retinoic acid (RA) on tumor growth, serum GH and insulin-like growth factor-1 (IGF-1) levels were examined in ovex rats. Latency of tumor growth was shortened, and tumor take and weight were promoted by all-trans RA both in the presence and absence of exogenous estrogen. Serum GH and IGF-1 levels became increased in tumor-bearing rats whereas PRL levels remained unchanged. Serum IGF-1 levels exhibited a good correlation with tumor weights (r = 0.84). Our results suggest a close relationship between increase of tumor weight and stimulation of serum IGF-1 level by RA in tumor-bearing rats. PMID- 1908850 TI - Analysis of cytosolic phosphoethanolamine and ethanolamine and their correlation with prognostic factors in breast cancer. AB - Availability of accurate prognostic factors is vital in making decisions on cancer therapy. We have measured the cytosolic contents of phosphoethanolamine and ethanolamine in tumor tissues of 53 breast cancer patients in an attempt to explore the possibility that these amines could be used as prognostic indicators. The levels of phosphoethanolamine and ethanolamine were determined by high performance liquid chromatography. The ratios of the molar quantity of these amines or amino acids to that of alanine plus tyrosine, which eluted as a single peak, were used to analyze and compare the results among different tumor samples. The results indicated that the values for phosphoethanolamine or ethanolamine varied significantly more than the values for amino acids, such as glycine plus threonine or glutamine plus serine (these amino acids were eluted as single peaks, respectively). The values for phosphoethanolamine, ethanolamine, and phosphoethanolamine plus ethanolamine were analyzed in relation to several commonly used prognostic factors of breast disease. The results indicated that groups having higher mitotic indices had significantly higher values for phosphoethanolamine or phosphoethanolamine plus ethanolamine than the group having lower mitotic indices. As the stage of the disease increased, the values for phosphoethanolamine plus ethanolamine also seemed to become higher. No correlation, however, was observed between steroid hormone receptor positive and negative groups or between positive and negative groups with regard to involved axillary lymph nodes. The content of phosphoethanolamine or phosphoethanolamine plus ethanolamine in cytosol therefore seems to be correlated with some prognostic indicators. PMID- 1908851 TI - Malignant cell detection in Burkitt's lymphoma using third-complementarity determining region (CDRIII), clone-specific probe developed by sequencing DNA from stored slides. AB - The DNA sequence of the third-complementarity-determining region (CDRIII) of the immunoglobulin heavy chain (IgH) gene in a case of Burkitt's lymphoma was determined by polymerase chain reaction (PCR) using template DNA extracted from a smear stored at room temperature for more than one year. The DNA sequence obtained from the stored slide was compared with that of DNA from a frozen lymph node biopsied at the initial presentation. The sequences were shown to be identical, implying that DNA from a smear on a stored slide can be used as a source of DNA for PCR amplification, sequencing, and development of a clone specific probe. Using oligonucleotides generated from one of the CDRIII sequences of the IgH gene as molecular probes, a retrospective study for the malignant clone on the smears was carried out. Malignant cells were detectable in the peripheral blood at an early stage of bone marrow relapse but not in the peripheral blood or bone marrow at the initial presentation. No malignant clone was detected in the bone marrow when testicular infiltration was diagnosed by examination of a pathological specimen. Thus, the technique permits molecular analysis of hematologic malignancies of B-cell lineage in cases where fresh or frozen specimens are not available. PMID- 1908852 TI - Risk of gastric remnant cancer in Japan. PMID- 1908853 TI - Antibiotic GE2270 a: a novel inhibitor of bacterial protein synthesis. I. Isolation and characterization. AB - A novel antibiotic, GE2270 A, was isolated from the fermentation broth of a strain of Planobispora rosea. The product was found to inhibit bacterial protein synthesis. Structural characteristics showed similarities between GE2270 A and thiazolyl peptides such as micrococcin which is known to inhibit protein synthesis by acting directly on the ribosome. Despite this similarity GE2270 A showed functional analogy to kirromycin-like antibiotics and pulvomycin, as its molecular target was found to be elongation factor Tu (EF-Tu). GE2270 A is active against Gram-positive microorganism and anaerobes and differs from the other EF Tu inhibitors in its spectrum of antimicrobial activity. PMID- 1908854 TI - Thiazocins, new aldose reductase inhibitors from Actinosynnema sp. 1. Fermentation, isolation and characterization. AB - New antibiotics designated as thiazocins A and B were isolated from the culture broth of Actinosynnema sp. C-304. Thiazocins A and B exhibited inhibitory activities against an aldose reductase from human placenta. PMID- 1908855 TI - The isolation of alpha-methylene-beta-alanine, a herbicidal microbial metabolite. PMID- 1908856 TI - Lupus anticoagulant, anticardiolipin antibody or antiphospholipid syndrome? PMID- 1908858 TI - Chloramphenicol versus ciprofloxacin in enteric fever. PMID- 1908859 TI - Inhibition of subtilisin BPN' by reaction site P1 mutants of Streptomyces subtilisin inhibitor. AB - It has been shown that the P1 site (the center of the reactive site) of protease inhibitors corresponds to the specificity of the cognate protease, and consequently specificity of Streptomyces subtilisin inhibitor (SSI) can be altered by substitution of a single amino acid at the P1 site. In this paper, to investigate whether similar correlation between inhibitory activity of mutated SSI and substrate preference of protease is observed for subtilisin BPN', which has broad substrate specificity, a complete set of mutants of SSI at the reaction site P1 (position 73) was constructed by cassette and site-directed mutagenesis and their inhibitory activities toward subtilisin BPN' were measured. Mutated SSIs which have a polar (Ser, Thr, Gln, Asn), basic (Lys, Arg), or aromatic amino acid (Tyr, Phe, Trp, His), or Ala or Leu, at the P1 site showed almost the same strong inhibitory activity toward subtilisin as the wild type (Met) SSI. However, the inhibitory activity of SSI variants with an acidic (Glu, Asp), or a beta branched aliphatic amino acid (Val, Ile), or Gly or Pro, at P1 was decreased. The values of the inhibitor constant (Ki) of mutated SSIs toward subtilisin BPN' were consistent with the substrate preference of subtilisin BPN'. A linear correlation was observed between log(1/Ki) of mutated SSIs and log(1/Km) of synthetic substrates. These results demonstrate that the inhibitory activities of P1 site mutants of SSI are linearly related to the substrate preference of subtilisin BPN', and indicate that the binding mode of the inhibitors with the protease may be similar to that of substrates, as in the case of trypsin and chymotrypsin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1908857 TI - Lupus anticoagulant. A report of 8 cases. AB - Eight cases with lupus anticoagulants (LA) were diagnosed over the last five years (1984-88). Of these, three were established cases of systemic lupus erythematosus (SLE), where bad obstetric history (2 cases) and recurrent deep venous thrombosis (DVT--1 case) prompted execution of laboratory tests for LA. In the remaining 5 cases, there was no clinical evidence of SLE. However, one case developed laboratory findings suggestive of SLE at a later date. One of these 5 patients was referred for unexplained abnormality in partial thromboplastin time (K). Three had recurrent abortions (one with additional history of DVT) while one had DVT with raised PTT (K). The clinical findings and laboratory tests by which lupus anticoagulants can be diagnosed have been discussed. PMID- 1908860 TI - Purification and characterization of a new GTP-binding protein of Mr 24,000 in bovine brain membranes. AB - A GTP-binding protein with an Mr of 24,000 was purified from a cholate extract of bovine brain membranes in addition to the previously reported alpha beta gamma trimeric GTP-binding proteins (G proteins). Partial amino acid sequence analysis of the purified 24-kDa protein revealed that it was not identical to any of the low Mr GTP-binding proteins already reported, but similar to the rac-gene products serving as the substrate of an ADP-ribosyltransferase (C3) purified from the culture medium of Clostridium botulinum type C. However, the 24-kDa protein was not ADP-ribosylated by the botulinum C3 enzyme. The 24-kDa protein was purified as a nucleotide-free form and characterized by the following unique properties distinct from those of alpha beta gamma-trimeric G proteins. (1) Mg2+ was essentially required for nucleotide binding to the 24-kDa protein; there was a progressive increase in its binding affinity for nucleotides as the concentration of the divalent cation was increased. (2) Nucleotides previously bound to the 24-kDa protein were rapidly dissociated from the protein in Mg(2+) free medium, in accord with the fact that the protein was indeed purified as a nucleotide-free form with Mg(2+)-free solutions. (3) The 24-kDa protein apparently exhibited much lower GTPase activity than do alpha beta gamma-trimeric G proteins because the product GDP was released from the 24-kDa protein in exchange for the substrate GTP only at a very low rate. Based on these findings, a possible role of the 24-kDa protein in cellular signalling is discussed in comparison with well characterized alpha beta gamma-trimeric G proteins. PMID- 1908862 TI - Update on nitrate therapy. PMID- 1908861 TI - Analysis of paralytic shellfish poisons by capillary electrophoresis. AB - A capillary electrophoresis (CE) method with UV detection is described for the separation and determination of underivatized toxins associated with paralytic shellfish poisoning (PSP). Confirmation of the electrophoretic peaks was facilitated by mass spectrometric (MS) detection using an ionspray CE-MS interface and by high-performance liquid chromatography with fluorescence detection. The determination of PSP toxins, such as saxitoxin and neosaxitoxin, in toxic dinoflagellates and scallops is demonstrated and comparisons are made with existing techniques. PMID- 1908863 TI - Relapsing native-valve enterococcal endocarditis: a unique cure with oral ciprofloxacin combination drug therapy. AB - Enterococcal endocarditis is the third most common presentation in native valves, and it is the most refractory. Unique among the streptococci, enterococci are relatively resistant to beta-lactam antibiotics requiring a combination aminoglycoside regimen for cure. Relapse is common even after apparently adequate therapy and may be seen in up to 25% of cases that involve streptomycin-resistant strains. This problem is magnified by the recent appearance of beta-lactamase producing strains of S. faecalis resistant to both ampicillin and gentamicin. Ciprofloxacin is being investigated with a number of antimicrobials in the attempt to identify superior protocols against troublesome pathogens. However, little published data is available concerning the clinical efficacy of this drug in enterococcal endocarditis. In vitro studies and preliminary trials with animal models have generally been disappointing with broth macrodilution time-kill or agar dilution proving the most reliable in vitro methods for predicting in vivo outcomes. The urgent need to identify new combination drug regimens is underscored not only by the development of new resistance patterns, but by the well-documented toxicities of conventional therapies. The authors present a case of relapsing enterococcal endocarditis caused by a non-beta-lactamase-producing strain of S. faecalis, which demonstrated high-level resistance to streptomycin but not to gentamicin. Relapses occurred despite favorable laboratory data and aggressive beta-lactam-gentamicin therapies. Cure was achieved using oral ciprofloxacin in a combination drug regimen, which is reported here for the first time. PMID- 1908865 TI - Binding of mutagens by fractions of the cell wall skeleton of lactic acid bacteria on mutagens. AB - The binding effect of cells and cell fractions, cell wall skeleton, cytoplasm, whole cells, and cell wall skeleton treated by lysozyme and alpha-amylase at 37 degrees C for 5 h, on Trp-P-1 (3-amino-1,4-dimethyl-[5H]pyrido [4,3-b]indole) and Trp-P-2 (3-amino-1-methyl-[5H]-pyrido[4,3-b]indole) were investigated. The cell and cell wall skeleton of Streptococcus cremoris Z-25 had greater binding activity, but cytoplasm and extract of cell wall skeleton did not bind Trp-P-1 and Trp-P-2. When the cells or cell wall skeleton were treated with lysozyme and alpha-amylase, unbound Trp-P-1 and Trp-P-2 concentrations were greater than that of the untreated control. It is possible that cell walls may be involved in the binding of mutagenic pyrolyzates to lactic acid bacteria. The cell wall skeleton of S. cremoris Z-25, Lactobacillus acidophilus IFO 13951, and Bifidobacterium bifidum IFO 14252 showed binding of Trp-P-1, 2-amino-6-methyldipyrido(1,2-a:3',2' d)imidazole, 2-amino-5-phenylpyridine, 2-amino-3-methylimidazo(4,5-f)quinoline, 2-amino-3,4-dimethylimidazo(4,5-f) quinoline, and 2-amino-3,8-dimethylimidazo(4,5 f)quinoxaline. The cell wall skeleton of S. cremoris group and Streptococcus lactis also showed the binding activity with A N-nitrosodimethylamine. The binding of Trp-P-1 to cell walls was very high, and the binding of mutagenic pyrolyzates was variable with different bacterial species. The peptidoglycan complex and polysaccharides liberated from cell wall skeleton of S. cremoris Z-25 showed strong binding of Trp-P-2. Peptidoglycans has a binding effect of about 19.86 micrograms/mg; polysaccharides had a binding effect of 14 micrograms/mg. PMID- 1908864 TI - Minimization of indomethacin-induced reduction in renal function by misoprostol. AB - A prospective, randomized, open-label, triple crossover comparison of the effects of indomethacin, misoprostol, or the combination, on renal function was performed to assess the ability of an oral prostaglandin E analogue, misoprostol, to minimize indomethacin-induced decline in renal function in middle-aged women. Twelve healthy women (mean age: 60.5 +/- 1.6 yr) with normal renal function (serum creatinine: 81 +/- 9 umol/L) were studied; six women were normotensive, and six women were hypertensive with their blood pressure controlled with 50-mg hydrochlorothiazide daily. All patients were placed on a 2-g sodium daily diet for 2 weeks before initiation of the study. The subjects were prospectively randomized to receive each of three 4-day treatments of indomethacin (25 mg q 6hr), misoprostol (200 mcg q 6hr), or the combination of drugs with a 4-day washout between each treatment period. Measurements of GFR (urine accumulation of 99mTc-DTPA) and RPF (serum disappearance 131I-Hippuran), and urine collections for electrolytes were obtained before the first treatment period and on the fourth day of each treatment period. Three of the six hypertensive patients and three of the six normotensive patients had a decrease (greater than 10%) in GFR associated with indomethacin therapy. When misoprostol was given with the indomethacin, four of these six patients did not experience a decline in GFR (baseline GFR for six patients: 75.4 +/- 6.6 mL/min/1.73m2, GFR after indomethacin: 57.8 +/- 9.5 mL/min/1.73m2, GFR with combination of indomethacin and misoprostol: 69.7 +/- 3.5 mL/min/1.73m2. RPF was not consistently altered by subacute/chronic dosing of indomethacin, misoprostol, or the combination of the drugs. The authors conclude that misoprostol ameliorates indomethacin-induced renal dysfunction in salt-restricted and diuretic-treated middle-aged women with normal serum creatinine. PMID- 1908866 TI - Lactose absorption by postweaning rats from yogurt, quarg, and quarg whey. AB - Lactose-intolerant postweaning rats were fed experimental diets including yogurt, quargs prepared from yogurt culture and buttermilk culture, and two types of whey obtained from quarg processing. After feeding each diet for a period of 7 d, absence of blood glucose elevation and occurrence of diarrhea were used as indicators of lactose malabsorption. Blood glucose assays and absence of diarrhea indicated that yogurt and quargs prepared from yogurt and buttermilk culture were well tolerated by the rats. Wheys containing the same levels of viable organisms and lactose as the quargs caused severe symptoms of diarrhea and poor lactose absorption as indicated by no changes in blood glucose levels. Plate counts and enzyme assays of gastrointestinal contents confirmed presence of viable culture organisms and beta-galactosidase activity after feeding the two types of quarg. The availability of viable organisms, the exogenous lactase activity, and especially the slow gastric emptying may all have contributed to more efficient hydrolysis and digestion of lactose from quargs and yogurt than from the wheys. PMID- 1908867 TI - First postpartum luteal function in dairy cows after ovulation induced by progestogen and gonadotropin-releasing hormone. AB - The objective was to determine the effects of progestogen treatment on the lifespan of the first corpus luteum induced by GnRH in periparturient-milked cows. Dairy cows (n = 55) were assigned randomly following normal parturitions to receive either a progestogen implant (6 mg of norgestomet) or a blank implant (control) for 6 d beginning 2 to 5 d after calving. Fifty micrograms of GnRH were administered i.m. 72 h after implant removal to induce ovulation. Concentrations of LH and FSH in serum from 24 to 30 h and from 66 to 72 h after implant removal were similar among treatments. The magnitude of LH released after GnRH injection was higher in progestogen-treated cows (7.6 +/- .9 ng/ml) than in controls (5.3 +/- .9 ng/ml). Concentrations of estradiol in serum from the beginning of the implant period until 3 d after GnRH injection were higher in cows receiving progestogen (9.1 +/- 1.7 pg/ml) than in controls (5.6 +/- 1.7 pg/ml). The proportion of cows that responded to GnRH (elevated concentrations of progesterone in serum greater than .5 ng/ml within 3 to 5 d after injection) tended to be higher in cows receiving progestogen (24 of 28) than in control cows (19 of 27). By definition, interval to first ovulation after GnRH injection was shorter in cows responding to GnRH (3.8 +/- .5 d) than in those failing to respond (20.2 +/- .9 d).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1908868 TI - Changing dietary electrolyte balance for dairy cows in cool and hot environments. AB - Two Latin square studies, each containing eight primiparous cows (four Holstein, four Jersey), were conducted to determine the effect of changing dietary electrolyte balance during cool and hot environmental conditions on performance of lactating dairy cows. Electrolyte balance, expressed as Na + K - Cl in milliequivalents per kilogram of diet, was altered by changing K and Cl content in the diet using potassium bicarbonate or calcium chloride. Maximum and minimum temperatures averaged 26.7 and 15.0 degrees C during the cool phase and 32.3 and 22.5 degrees C during the hot phase of the study. Milk yield improved linearly with increasing electrolyte balance with nonsignificant treatment by phase interaction, whereas DMI of cows improved quadratically with increasing dietary electrolyte balance. A treatment by phase interaction for DMI was detected, although intake of DM reached a plateau at a similar dietary electrolyte balance during the cool and hot phases. Body (milk) temperature of cows appeared to be related to the level of feed consumed and varied by treatment within phase. Body (milk) temperature was higher during the hot phase of the experiment. Blood bicarbonate and pH were lowest in cows offered the low electrolyte balance (high Cl) diet, and blood and urinary Na + K-Cl increased linearly with increasing dietary electrolyte balance. The response to dietary electrolyte balance appeared to be mediated through blood buffering and the impact on physiologic systems of the cow. PMID- 1908869 TI - Antagonism of PAF and arachidonic acid by ketotifen. PMID- 1908871 TI - Interactive image analysis system to determine the motility and velocity of cyanobacterial filaments. AB - An interactive image analysis system has been developed to analyse and quantify the percentage of motile filaments and the individual linear velocities of organisms. The technique is based on the "difference" image between two digitized images taken from a time-lapse video recording 80 s apart which is overlaid on the first image. The bright lines in the difference image represent the paths along which the filaments have moved and are measured using a crosshair cursor controlled by the mouse. Even short exposure to solar ultraviolet radiation strongly impairs the motility of the gliding cyanobacterium Phormidium uncinatum, while its velocity is not likewise affected. These effects are not due to either type I (free radical formation) or type II (singlet oxygen production) photodynamic reactions, since specific quenchers and scavengers, indicative of these reactions, failed to be effective. PMID- 1908870 TI - Binding shift assay of parvalbumin, calmodulin and carbonic anhydrase by high performance capillary electrophoresis. AB - Shifts in mobility caused by binding of Ca2+ to calmodulin and parvalbumin were studied using high-performance capillary electrophoresis in a Tris-glycine buffer, rather than conventional polyacrylamide gel electrophoresis which requires larger amounts of sample and longer assay time. A Zn(2+)-binding protein, carbonic anhydrase, also showed a partial shift in mobility following Zn(2+)-binding. PMID- 1908872 TI - Separation of glutaraldehyde and some of its aldol condensation products by hydroxyl-aldehyde group affinity chromatography. AB - Glutaraldehyde exists in aqueous solution in equilibrium with monomers and polymers of cyclic and open-chain hemialdals and hydrates. At alkaline pH oligomeric and polymeric alpha,beta-unsaturated aldehyde derivatives are formed from primarily produced aldol condensation products. This communication reports a method for separation of such aldol condensates by means of a new high performance liquid chromatography technique based on the affinity of aldehyde groups for hydroxyl groups of a hydroxylated polyether matrix (Bio-Gel SEC-10). Five peaks corresponding to different aldol condensates of glutaraldehyde were obtained from the affinity column. They have been distinguished by 1H-NMR and UV spectroscopy. Kinetic measurements yielded formation rates for the different aldol condensates. PMID- 1908873 TI - Rupture of the flexor pollicis longus in von Recklinghausen's disease. AB - An unusual cause of inability to flex the interphalangeal joint of the thumb in a patient with von Recklinghausen's disease is reported. A tumor in the cubital fossa and the basic characteristics of this disease led to a preoperative misdiagnosis of anterior interosseous nerve paralysis. However, surgical exploration and histological examination showed that the correct diagnosis was rupture of the flexor pollicis longus tendon caused by intratendinous proliferation of a neurofibroma. This is the first report in the English-language literature of a flexor tendon rupture caused by intratendinous tumor proliferation. PMID- 1908874 TI - Diagnostic Mr 31/32000 proteins of Schistosoma mansoni (Sm31/32) and S. haematobium (Sh31/32): stability and reaction conditions for prospective field tests. AB - The existence of adult Schistosoma haematobium worm proteins (Sh31/32) homologous to the diagnostic Sm31/32 of S. mansoni is shown. Sm31/32 and Sh31/32, adsorbed on nitrocellulose and kept dry on the bench before immunoblot analysis, were antigenically stable for at least 4 years including storage for 17 months in tropical climates. The antigens react with patient sera in the absence of defined buffers under rather simple conditions ("humid chamber blot"). The results add to the use of these antigens for serodiagnosis of schistosomiasis in endemic areas. PMID- 1908875 TI - Protective and other biological properties of Bacillus anthracis soluble antigens. AB - The soluble antigens were explored of the culture filtrate (CF) derived during static growth of B. anthracis vaccine strain 34F2 on a medium containing casein hydrolysate. Electrofocusing of CF preparations revealed that the protective activity was distributed over a wide range of pH 3-7. The most pronounced and stable protective activity was observed at pH 4.6-4.8. Following toxin factors were isolated and identified: protective antigen (87 kD), oedema factor (87 kD) and lethal factor (78-81 kD). The greatest protective activity was associated with antigens characterized by a molecular weight of 78-87 kD and toxic activity. Preparations of the oedema and lethal factors had the same protective activity as protective antigen (PA) preparations. Other CF soluble antigens protected about 30% of immunized guinea pigs. A protein was isolated with a molecular weight of 80 kD and isoelectric point at pH 5.3-5.7 which was not toxic and did not form toxic mixtures in association with other toxin factors; this protein featured a high immunogenic activity, however, it protected only 31% of immunized animals. Factors are analyzed which determine differences in the protective effects of live and chemical vaccines. PMID- 1908876 TI - VH gene analysis of spontaneously activated B cells in adult MRL-lpr/lpr mice. J558 bias is not limited to classic lupus autoantibodies. AB - To determine the genetic origins of lupus auto-antibodies, we analyzed the relationship between VH gene usage and auto-Ag-binding properties of 352 B cell hybridomas derived from MRL-lpr/lpr mice. The hybridomas were derived from neonatal, 1-month-old, 3-month-old, and 6-month-old mice. The experimental strategy provided that the hybridomas were monoclonal at initial evaluation, so the Ag binding and V gene frequencies of the entire population could be determined. Initially, 1032 Ig-producing hybridomas were evaluated for binding to six Ag; VH gene family use was determined in 119 anti-DNA and anti-rabbit thymus extract (RTE) antibodies (autoantibodies) and in 233 age-matched Ig that did not bind to any of the six Ag (nonbinders). Neonatal B cells, including cross reactive IgM autoantibodies and nonbinder IgM, used relatively 3' VH genes. The majority of B cells in adult mice used VH genes of the J558 family. Although J558 use was significantly higher among the autoantibodies (anti-DNA and anti-RTE) than among the nonbinder Ig, this difference was due to a higher frequency of J558 use by 1-month-old mice. At 3 months, J558 use by the nonbinder Ig increased to the same frequency of J558 use as in the autoantibody population. J558 use in both groups of antibodies exceeded a previously reported estimation of J558 expression in the functional B cell repertoire of young adult MRL-lpr/lpr mice. Several subgroups of antibodies that share properties with pathogenic Ig, including IgG, cross-reactive Ig, and anti-dsDNA autoantibodies, demonstrated a marked preferential expression of the J558 family. These results suggest that there is an age-related bias in the activation of B cells using J558 VH genes in MRL-lpr/lpr mice that is under the influence of a selective force distinct from, or in addition to, an ssDNA or RTE auto-Ag-driven response. PMID- 1908878 TI - Interactions among granulocyte-macrophage colony-stimulating factor, macrophage colony-stimulating factor, and IFN-gamma lead to enhanced proliferation of murine macrophage progenitor cells. AB - This report examines the actions of IFN-gamma on monocytopoiesis in murine liquid and semisolid bone marrow cultures. The proliferative response of bone marrow cells to macrophage CSF and granulocyte-macrophage CSF was assayed by measuring [3H]TdR uptake in a range of mouse strains. No interstrain difference in kinetics was observed for CSF-1 action, but GM-CSF acted significantly more rapidly on C57B1/6, Swiss, and to a lesser extent A/J mice than on BALB/c or CBA. IFN-gamma inhibited [3H]TdR incorporation elicited by CSF-1, and to a much lesser extent, GM-CSF. When the two CSF were added together, the effects were not additive; in fact, the response was the same as that seen with GM-CSF alone. When IFN-gamma was also added, the response was restored to the level seen with CSF-1 alone. In essence, the inhibitory actions of GM-CSF and IFN-gamma were mutually exclusive. The mechanism of these actions was investigated using colony assays. As expected, CSF-1 caused the formation of pure macrophage colonies, whereas GM-CSF stimulated production of macrophage, granulocyte, and mixed granulocyte macrophage colonies. When the two CSF were added in combination, the total colony count was greater than with either alone, but less than additive. The number of pure macrophage colonies was reduced to the number seen with GM-CSF alone. IFN-gamma reduced the number of colonies in the presence of CSF-1, but slightly increased the number with GM-CSF. In the presence of both CSF, IFN-gamma increased the colony count by around 25 to 40%, so that the numbers were greater than the combined total of CSF 1 plus GM-CSF added separately. Similar results were obtained in all mouse strains tested. The results suggest that the thymidine uptake data reflect changes in the number of progenitor cells responding rather than changes in cell cycle time. The results are discussed in terms of the possibility that coadministration of GM-CSF and CSF-1 could ameliorate the myelosuppressive actions of IFN-gamma in vivo, leading to more effective use of this agent as a biologic response modifier. PMID- 1908877 TI - Cytokine cytotoxicity against oligodendrocytes. Apoptosis induced by lymphotoxin. AB - The cytotoxic effect of recombinant human cytokines was tested on glial cells cultured from mature bovine brain. Lymphotoxin (LT) and TNF induced injury to oligodendrocytes in a time and dose-dependent fashion. The other cytokines tested, IFN-gamma, IL-6, and IL-2, did not affect oligodendrocytes in culture over a 72-h observation period. None of the cytokines injured astrocytes cultured from the same source. LT showed a much more potent cytotoxicity than TNF toward oligodendrocytes; cytotoxic changes were noted earlier (24 h) and at lower units of activity. Morphologic studies showed that the LT-mediated effects were associated with early retraction of cell processes, depolymerization of F-actin and subsequent nuclear degeneration. Lack of early cytoplasmic membrane injury as measured by 51Cr release and electron microscope studies demonstrating nuclear disintegration suggested an apoptotic mechanism of oligodendrocyte injury evoked by LT, which was supported by DNA integrity assay. These results demonstrate that LT possesses potent cytotoxic activity against oligodendrocytes and that the major mechanism involved in this process is DNA fragmentation. PMID- 1908879 TI - Rap1A is a substrate for cyclic AMP-dependent protein kinase in human neutrophils. AB - The Ras-related protein, Rap1B, has previously been shown to serve as a PKA substrate in vitro and to be phosphorylated by cAMP elevating agents in human platelets. We have purified a Rap1 protein that serves as a PKA substrate from human neutrophils, and we now identify this protein as Rap1A. A 23-kDa protein that co-migrated with recombinant Rap1A was phosphorylated in electroporated human neutrophils upon stimulation by cAMP in the presence of [gamma-32P]ATP. This protein could be immunoprecipitated by the Rap1A/B-specific antibody, R61. The 23-kDa phosphoprotein was monitored during the purification of Rap1 from neutrophil membrane extracts and was shown to copurify with Rap1 during the DEAE Sephacel, heptylamine Sepharose, and MonoQ chromatography steps utilized. The purified protein was phosphorylated to an extent of 1 mol phosphate/mol GTP gamma S bound. This protein was identified as Rap1A by: 1) amino acid sequence analysis; and 2) immunoblotting with a Rap1A-specific antibody. The amino acid phosphorylated on Rap1A by PKA was a serine residue. The site of phosphorylation was indicated by carboxypeptidase digestion and confirmed using a mutant recombinant Rap1A lacking the relevant serine (serine-180). Rap1A, not Rap1B, appears to be the major 23-kDa PKA substrate in human neutrophils. It is possible that Rap1A plays a role in human neutrophils in mediating the inhibitory effects of cAMP-elevating agents upon chemoattractant-stimulated cell activation. PMID- 1908880 TI - Restricted Ig H chain V gene usage in the human antibody response to Haemophilus influenzae type b capsular polysaccharide. AB - The mechanisms that govern the content of the human antibody repertoire are poorly understood. To investigate the antibody response to a clinically relevant Ag, we have produced heterohybridomas secreting human antibodies directed against the capsular polysaccharide of Haemophilus influenzae type b (Hib PS). Immune lymphocytes were harvested 7 days after immunization with either of two vaccine formulations, a plain polysaccharide vaccine (Hib PS) or a polysaccharide-protein conjugate of Hib PS and diphtheria toxoid (Hib PS-D). H chain V region gene nucleic acid sequences were determined for five stable hybridomas. All use members of the VHIII gene family and are 83% to 98% homologous to two candidate germ-line sequences. A variety of D and JH segments are used. Thus the Ig H chain repertoire appears to be restricted to a limited group of VHIII family members. The previously reported expression of homologous sequences in the human fetal repertoire suggests that the inability of young children to respond to this Ag is not caused by deficiencies of these important elements early in development. The restricted use of VHIII gene segments suggests that this gene family plays a pivotal role in the immune response to this important childhood pathogen. PMID- 1908881 TI - Many variable region genes are utilized in the antibody response of BALB/c mice to the influenza virus A/PR/8/34 hemagglutinin. AB - We have examined how many different H chain variable (VH) and kappa-chain variable (Vk) germ-line genes are used in the antibody response to the influenza virus A/PR/8/34 hemagglutinin (PR8 HA), and have assessed how the expression of individual VH and/or Vk genes contributes to the generation of specificity for the HA. A panel of 51 hybridoma antibodies that recognize two antigenic regions on the HA were compared for the sequence of their Ig H and L chain V regions. The hybridomas were obtained from 28 individual BALB/c mice that had been immunized with PR8 under a variety of primary and secondary response immunization protocols. The degree and pattern of sequence similarity suggests that 29 different VH genes drawn from seven different VH gene families, and 25 different Vk genes drawn from 12 different Vk gene families were used in this panel. Based on current estimates of the total numbers of VH and Vk genes in the mouse, this suggests that between 2.5 and 10% of the entire VH and Vk germ-line repertoires were used by these hybridomas. Despite this extensive diversity, some V genes were repetitively identified among these hybridomas, and were most often expressed in the context of specific VH/Vk combinations. Because antibodies that used identical VH/Vk combinations also usually displayed similar reactivity patterns with a panel of mutant viruses, this indicates that VH/Vk pairing can be important in establishing the specificity of antibodies for the HA. PMID- 1908882 TI - Identical V region amino acid sequences and segments of sequences in antibodies of different specificities. Relative contributions of VH and VL genes, minigenes, and complementarity-determining regions to binding of antibody-combining sites. AB - By examining a large database of amino acid sequences of antibodies of various specificities, we have found that many antibodies of distinctly different specificities assemble identical VL domains with different VH domains. In contrast, rarely is the same VH domain found in sets of antibodies of different specificities. We identified additional sets of antibodies of different specificities and identical sequences covering amino acid residues VH 1 to 94 and VL 1 to 95. In addition, there were segments of additional antibodies for which complete sequences were not available, but identities were seen in VL CDR1, VL CDR2, and VL CDR3 up to the VL-JL junction. The finding that there are many identical VL 1 to 95 segments with different VH 1 to 94 sequences, and vice versa, raises important questions as to the role of VH in influencing the conformation of VL and, conversely, the role of VL in influencing the conformation of VH. Evidence is also cited indicating that a single amino acid change may seriously disrupt site structure and in some instances abolish binding. Our findings suggest that it will be important in the future to investigate further conformational effects on antibody structure by using X-ray crystallography, nuclear magnetic resonance spectroscopy, or other methods, to obtain a better understanding of the functions and topography of antibody combining sites. PMID- 1908883 TI - Multiple mechanisms participate in the generation of diversity of human H chain CDR3 regions. AB - The area of highest variability in the antibody-combining site is the third complementarity determining region or CDR3. Based on our preliminary observation of the tremendous variability of this region in the human system we have studied the potential of CDR3 regions for generating diversity in the human B cell repertoire. To this end we generated CDR3-specific cDNA libraries from tissues collected at several stages of human development. Detailed computer analysis of more than 500 sequences reveals that human CDR3 region have the potential to generate more than 10(14) different peptides. The mechanisms responsible for this diversity include rearrangement by inversion, D-D fusion, gene conversion and the frequent utilization of the recently described DIR genes. The specific recombination mechanisms which may explain aberrant rearrangements as well as differences between fetal and adult repertoires are discussed in detail. PMID- 1908884 TI - Cost analysis of two implantable narcotic delivery systems. AB - This survey compares costs of two commonly utilized implantable narcotic delivery systems. The systems are classified into type-I (exteriorized system using the DuPen epidural catheter) and type-II (implanted system using the Synchromed pump). Costs were analyzed by reviewing actual patient hospital financial service records and Homecare vendor quotations. From the perspective of cost analysis alone, we conclude that savings accrue when patients requiring treatment beyond 3 months duration are managed with a type-II implanted system compared with a type I system with an external pump. PMID- 1908885 TI - [The first two cases of tsutsugamushi disease found in Toshima Island, Tokyo Metropolis]. AB - It has been known that tsutsugamushi disease, so-called "Shichito-fever", is widely spread among the Izu Islands, Tokyo Metropolis. The cases were reported in Oshima Island, Niijima Island, Shikine Island, Kozu Island, Miyake Island, Mikura Island, and Hachijo Island previously, although no case has been reported in Toshima Island. In this paper, we report the first two cases of tsutsugamushi disease found in Toshima Island in December 1988 and December 1989. The first case was a 73 year-old male and the second case was a 83 year-old female, respectively. Fever, erythema and eschar were observed in both cases, while lymphadenopathy and hepatosplenomegaly were not detected. After tetracycline was administered, the fever immediately went down and erythema gradually disappeared in both cases. Specific immunofluorescence tests demonstrated that IgG antibody titers rose against Karp, Gilliam and Kato strains, and that IgM antibody titers rose only against Gilliam strain in both cases. Therefore, Gilliam-like strain of Rickettsia tsutsugamushi may play an important role in Toshima Island. PMID- 1908886 TI - Nurses and physicians on nutritional support: a comparison. AB - During the last decade, several court cases have focused attention on the moral and legal aspects of withholding or withdrawing food and fluids from certain patients. The courts have not been unanimous in their judgements on these matters. In attempting to explore this issue, this article reviews both the nursing and medical literature on the withdrawing and withholding of food and fluids with particular attention to empirical studies. Several themes which emerge from the literature are used to explore the similarities and differences between the practices of nursing and medicine where nutritional support is concerned. PMID- 1908887 TI - Orchestrating social change: an imperative in care of the chronically ill. AB - The ethical challenges of caring for the chronically ill are of increasing concern to nurses as they attempt to create humanitarian environments for long term care. This article suggests two ethical perspectives to guide the agenda of the nursing profession to achieve social change in the care of the chronically ill and aging. First, a reemphasis on the public duties of the professions is recommended which extends beyond serving the interests of the nursing profession to recognizing the need to serve the common good. Second, the limitations of the autonomy paradigm are explored and the foundation for the development of a new moral paradigm is analyzed in terms of its' potential usefulness in addressing ethical problems of chronic illness. Several initiatives that nursing must undertake to facilitate the emergence of this paradigm are proposed. PMID- 1908889 TI - A prospective study of post-transfusion non-A, non-B (type C) hepatitis following cardiovascular surgery in Taiwan. AB - In an attempt to investigate the incidence and clinical course of non-A, non-B (NANB) hepatitis following blood transfusion in Taiwan, 288 patients who underwent cardiovascular surgery and received blood transfusion were followed prospectively with serum liver aminotransferase levels and viral hepatitis markers for at least six months. None had any past history of liver disease or drug abuse. All blood donors were tested for serum hepatitis B surface antigen and alanine aminotransferase (ALT) (greater than 45 U/L). Thirty-seven (12.8%) patients developed PTH. 34 (91.9%) were considered to be cases of NANB hepatitis, 2 (5.4%) were cytomegalovirus hepatitis, and one (2.7%) was caused by Epstein Barr virus. No one developed hepatitis B post-transfusion hepatitis (PTH). Of the 34 NANB PTH patients, 15 (44.1%) were asymptomatic, 16 (47.1%) had clinical symptoms, and 9 (26.5%) had serum total bilirubin levels higher than 2 mg/dl. There was no case of fulminant hepatic failure. Of 26 NANB PTH patients who were followed up for more than one year, 15 (57.7%) still had abnormal serum ALT levels. The incubation period of NANB PTH ranged from 2 to 16 (mean 6.1 +/- 3.2) weeks. Of the 37 PTH patients, 32 (86.5%) were found to have anti-HCV seroconversion during one year follow-up period. NANB PTH is as common in Taiwan as in the United States and Japan, and is demonstrated by this study to be due mostly to HCV. PMID- 1908888 TI - Evidence for temporal coupling of growth hormone, prolactin, LH and FSH pulsatility overnight during normal puberty. AB - The patterns of secretion of GH, LH, FSH and prolactin were determined over a single night (20.00-08.00 h; 15-min sampling) in 34 normal subjects (17 male, 17 female, aged 9.1-20.9 years). Plasma GH was measured by an immunoradiometric assay and LH, FSH and prolactin by radioimmunoassay in all samples. Data were analysed by Fourier transformation and cross-correlation after stationarization. The highest mean GH levels were noted in girls at Tanner stage 2/3 and in boys at stages 4/5. Prolactin levels were highest in girls at stage 4/5 and in boys at stage 2/3. LH and FSH showed a progressive rise by puberty stage in both sexes. The dominant pulse periodicities of GH and prolactin were 150-180 min in girls and 180 min in boys. LH and FSH pulse periodicity was around 90 min in early puberty and 180 min in later puberty in both sexes. LH and prolactin pulses showed a phase relationship with GH with a lag of 30-75 min (r = 0.32; P less than 0.001) and 30 min (r = 0.47; P less than 0.0001) respectively. Generally, LH and prolactin pulses were in phase (r = 0.42; P less than 0.0001) and there was a highly significant correlation (r = 0.64; P less than 0.0001) between FSH and LH pulsatility. Whereas mean overnight concentrations and pulse periodicity of the principal pituitary hormones varied between the sexes during early puberty, by the end of puberty a dominant pulse periodicity of around 150-180 min was established and there was remarkable temporal coupling of pulsatility. PMID- 1908890 TI - Reversible operculum syndrome caused by progressive epilepsia partialis continua in a child with left hemimegalencephaly. AB - In a child with left hemimegalencephaly and seizures, a reversible operculum syndrome developed when continuous epileptic discharges spread from the left hemisphere to the contralateral central regions. The operculum syndrome lasted for three months until left hemispherectomy was performed. Soon after surgery the seizures and the operculum syndrome resolved. The operculum syndrome is a facio pharyngo-glosso-masticatory diplegia usually due to structural lesions in both opercular regions. The reversibility of the syndrome in the reported case demonstrates that the operculum syndrome is sometimes functional rather than lesional. PMID- 1908891 TI - Duration of etidronate effect demonstrated by serial bone scintigraphy. AB - There have been several reports of etidronate disodium (EHDP) interference upon the biodistribution of 99mTc-methylene diphosphonate (MDP). With the increasing use of etidronate for the treatment of Paget's disease, hypercalcemia, and osteoporosis, nuclear physicians can expect to encounter increasing numbers of cases in which EHDP-induced artifacts impair the diagnostic utility of bone scans. The temporal duration of this effect is unknown yet obviously important. We report serial bone scintigraphy in a patient who received a single dose of EHDP for hypercalcemia. Normal biodistribution of 99mTc-MDP was noted at 15 days, suggesting that 2 wk are sufficient before performing a bone scan after a single intravenous dose of etidronate. PMID- 1908892 TI - Malnutrition induces an increase in intermediate filament protein content of rat cerebral cortex. AB - Wistar rats were fed a normal protein (25% casein) or an isoenergetic low protein (8% casein) diet from the day of giving birth until pups were weaned. Some litters were killed at weaning; others (both normal and malnourished animals) received the 25% protein diet until d 90 when they were killed. Intermediate filament (IF) preparations were obtained by extraction of the cerebral cortex with a high salt PBS solution containing 1% Triton X-100. The pellet contained the bulk of the cytoskeleton proteins from tissue, identified as the 150- and 68 kDa subunits of neurofilaments (NF-M and NF-L, respectively), the 66-kDa associated protein, the 57-kDa intermediate filament-like protein, and the 50-kDa glial fibrillary acidic protein. Intermediate filament-enriched fractions from control and malnourished rats at both d 21 and 90 were scanned following two dimensional gel electrophoresis to determine the effects of postnatal malnutrition on the intermediate filament protein content. The results indicated that postnatal malnutrition imposed during the brain growth spurt period did not alter the expression of IF proteins of the cerebral cortex in 21-d-old rats, but increased the expression of NF-L and NF-M proteins in adult rats. PMID- 1908893 TI - Enhancement of primary systemic acquired immunity by exogenous triiodothyronine in wasted, protein-energy malnourished weanling mice. AB - The objectives of this investigation were to expand information regarding the types of acquired immune responses that can be stimulated by triiodothyronine (T3) supplements in wasting protein-energy malnutrition (PEM) and to determine whether T3 can exert its enhancing influence on acquired immunity in PEM against diverse genetic backgrounds. Two experiments were conducted with weanling C57BL/6J mice. Animals were allowed ad libitum access for 14 d to a nutritionally complete purified diet (C), an isoenergetic low protein (0.6%) formulation (LP) or the low protein diet containing 0.2 microgram T3/g (LPT3). The LP diet produced wasting as judged by weight loss and carcass composition. This diet also depressed both the antibody response to sheep red blood cells (Experiment 1) and the complete major histocompatibility complex-disparate skin graft rejection response (Experiment 2). The LPT3-fed mice experienced wasting at least equivalent in magnitude to that of animals fed LP, but they exhibited significantly more vigorous responses than LP-fed animals in both immune reactions examined. In conjunction with previous results obtained using the CBA/J strain of mouse, the results show that not only humoral (antibody) responses but also at least some cell-mediated responses can be improved by T3 supplements in wasting PEM. Moreover, this influence on acquired immunity is apparent in at least two genetically unrelated mouse strains, thus increasing confidence in its basic biological significance. PMID- 1908894 TI - Effects of intravenous nutrition on lipoprotein metabolism, body composition, weight gain and uremic state in experimental uremia in rats. AB - The effect on serum lipids, lipoprotein fractions, body composition, weight gain and uremic state of including fat in intravenous nutrition was evaluated in rats with chronic uremia. Uremic rats were given high energy (1385 kJ.kg body weight 1.day-1), low nitrogen (0.6 g N.kg body weight-1.day-1) total parenteral nutrition (TPN) for 12 d with either glucose or glucose plus 30% lipids (Intralipid) as the energy source. Additional uremic and nonuremic groups were fed a standard diet orally. During TPN, serum triglyceride and cholesterol levels were slightly higher in rats fed lipid-based TPN compared to those administered glucose-based TPN or fed the oral diet; but there were no differences 8 h after feeding. The serum lipoprotein fractions showed accumulation of lipids in LDL resulting from the lipid-based TPN but no differences in VLDL. In orally fed uremic rats, more lipids were found in HDL than in the TPN-treated rats. The fractional clearance of the fat emulsion was normal and independent of the nutrition composition. Uremic rats administered lipid-based TPN for 21 d had the same weight gain as orally fed, nonuremic control rats (23 +/- 3 vs. 22 +/- 2%); glucose-based TPN did not support normal growth (10 +/- 1%). Uremic rats fed orally did not grow and retained significantly more body water than TPN-fed uremic rats. In uremic animals, lipid-based TPN also was associated with normal body composition despite significantly lower levels of carnitine in plasma, skeletal muscle and heart tissue.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1908895 TI - Selenium status of preterm infants fed human milk, preterm formula, or selenium supplemented preterm formula. AB - The selenium status of 46 orally fed vitamin E-sufficient preterm infants (birth weight less than 1700 gm) was studied longitudinally for 3 weeks to determine the efficacy of selenium supplementation. Infants were fed either human milk (n = 21; 24 ng selenium/ml), preterm formula (n = 13; 7.8 ng selenium/ml), or preterm formula supplemented with sodium selenite (n = 12; 34.8 ng selenium/ml). Plasma and erythrocyte selenium and glutathione peroxidase activity and urinary and dietary selenium content were evaluated on study day 1 (day enteral feeds reached 100 kcal/kg/day) and weekly for 3 weeks. Throughout the study, selenium intakes of infants fed preterm formula plus sodium selenite were greater than those of infants fed human milk, which were greater than those of infants fed preterm formula (p less than 0.001). After 3 weeks no differences were observed among groups for plasma or erythrocyte selenium or glutathione peroxidase. Plasma selenium and glutathione peroxidase values within all groups were low compared with those reported for term infants fed human milk. Whereas urinary selenium levels of infants fed preterm formula plus sodium selenite were greater than those of infants fed preterm formula at weeks 1 and 2 (p less than 0.01), infants fed human milk and preterm formula had lower levels at week 3 than on study day 1 (p less than 0.05). We conclude that blood selenium measurements typically used to monitor selenium status do not reflect dietary selenium intakes of orally fed preterm infants. PMID- 1908896 TI - Factor VIII response to vasopressin in nephrogenic diabetes insipidus. PMID- 1908897 TI - Temperature regulation of the cryptococcal phenoloxidase. AB - Melanin formation at 37 degrees C has been proposed as a virulence factor in Cryptococcus neoformans. However, whereas catecholamine uptake is maintained at this temperature, phenoloxidase, which catalyses the oxidation of catecholamine to melanin, is severely decreased in most wild type strains cultivated at 37 degrees C. PMID- 1908898 TI - Liposome-encapsulated antibiotics: preparation, drug release and antimicrobial activity against Pseudomonas aeruginosa. AB - Ticarcillin- and tobramycin-resistant strains of Pseudomonas aeruginosa were shown to have a markedly increased sensitivity to antibiotics enclosed in liposomes. This was demonstrated by growth inhibition of two resistant P. aeruginosa strains in the presence of the liposome-enclosed ticarcillin and tobramycin at 2 per cent and 20 per cent of their respective minimum inhibitory concentration. The liposome-enclosed antibiotic was as effective against the beta lactamase-producing strain as against the non-beta-lactamase producing strain. Entrapment efficiency of the two antibiotics with the dehydration-rehydration vesicle (DRV) method was largely superior to other methodologies used. Kinetic studies with DRV demonstrated that tobramycin and ticarcillin-loaded liposomes still contained 83 per cent and 67 per cent of drug respectively after 24 h at 37 degrees C. PMID- 1908899 TI - Genetic recombination in Streptomyces michiganensis DSM 40,015 revealed three genes responsible for the formation of melanin. AB - By UV and NTG mutagenesis numerous auxotrophic, antibiotic-resistant and melanin negative mutants were isolated from Streptomyces michiganensis DSM 40,015 which proved to possess a efficient photoreactivation system. Using a mel- test strain with three auxotrophic markers and a antibiotic resistance for crosses with numerous prototrophic mel- strains three classes of mutants (melA, melB and melC) could be found. This classification was further supported by a series of crosses. The melC locus seemed to correspond to the melC locus of S. glaucescens which contains the tyrosinase structural gene. PMID- 1908900 TI - Use of alpha-aminoadipate and lysine as sole nitrogen source by Schizosaccharomyces pombe and selected pathogenic fungi. AB - alpha-Aminodipate, an intermediate of the lysine biosynthetic pathway of fungi, or lysine when used as the sole nitrogen source in the medium was growth inhibitory and toxic to Saccharomyces cerevisiae. The fission yeast Schizosaccharomyces pombe and pathogenic fungi Candida albicans, Filobasidiella neoformans and Aspergillus fumigatus grew in the medium containing alpha aminoadipate as the sole nitrogen source. C. albicans, A. fumigatus, and one of the strains of F. neoformans also grew in the medium containing lysine as the sole nitrogen source. When grown in the alpha-aminoadipate medium, only S. pombe accumulated a significant amount of alpha-ketoadipate in the culture supernatant. Also, 14C-alpha-aminoadipate was converted to 14C-alpha-ketoadipate in vivo. In the ammonium sulfate medium, S. pombe cells converted 14C-alpha-aminoadipate to lysine. The levels of glutamate-alpha-ketoadipate transaminase, an enzyme responsible for the conversion of alpha-aminoadipate to alpha-ketoadipate, and alpha-aminoadipate reductase, an enzyme required for the conversion of alpha aminoadipate to lysine, were similar in S. pombe cells grown in the alpha aminoadipate or ammonium sulfate medium. However, the level of homoisocitrate dehydrogenase, an enzyme before the alpha-ketoadipate step, was twelvefold lower in S. pombe cells grown in the alpha-aminoadipate medium compared to the level in cells grown in the ammonium sulfate medium. Pathogenic fungi used in this study did not accumulate alpha-ketoadipate and alpha-aminoadipate-delta-semialdehyde when grown in medium containing alpha-aminoadipate and lysine, respectively, as sole nitrogen source. However, only pathogenic fungi used both lysine and alpha aminoadipate as sole nitrogen source. This unique metabolic property could be useful for the identification of these pathogens. PMID- 1908901 TI - Polyhydroxylated phenylacrylic acid derivatives as new anti-tumor agents. AB - Preliminary evidence indicates that antitumor agents containing the o dihydroxybenzene moiety exhibit enhanced antitumor activity toward malignant cells of high oxidative potential, such as melanoma cells. Based on this consideration, 11 hydroxybenzene acrylic acid derivatives of differing redox potential were prepared as potential substrates for the melanoma specific enzyme tyrosinase, that might exhibit general antitumor activity and enhanced cytotoxicity toward melanoma cells. Five of these compounds [alpha-cyano-beta-(4 hydroxyphenyl)-, alpha-cyano-beta-(3,4-dihydroxyphenyl)-, and alpha-cyano-beta (3,4,5-trihydroxyphenyl)acrylic acid (THPPA), and 3,4-dihydroxy- and 3,4,5 trihydroxybenzalcyanoacetamide] were found to be substrates for tyrosinase with Km values from 0.08 to 4.13 mM and Vmax values from 0.18 to 3.02. These data indicate that as the number of hydroxy groups increases, the rate of oxidation increases, and that cyanoamides were faster reacting than corresponding cyanoacids, with dicyanides the least reactive. In contrast, cyanoamides were less effective as substrates than cyanoacids. In vitro studies showed all but two compounds were active against L1210 (IC50 range 21-980 microM), SK-MEL-28 (IC50 range 54-950 microM), and SK-MEL-30-3 (IC50 range 54-190 microM). Only THPPA was active in vivo against L1210 and B-16 melanoma. PMID- 1908902 TI - Evolution of amitosis of the ciliate macronucleus: gain of the capacity to divide. AB - Ciliates exhibit nuclear dimorphism, i.e. they have a germline micronucleus and a somatic macronucleus. Macronuclei are differentiated from mitotic sisters of micronuclei. The macronuclei of "higher ciliates" are polyploid and divide acentromerically ("amitotically"); they differentiate once per life cycle. By contrast, Karyorelict (KR) ciliate macronuclei are nearly diploid and cannot divide; they must differentiate at every cell cycle. Diverse lines of evidence are presented to support the hypothesis that ancestral ciliate macronuclei were incapable of division (as in living karyorelict ciliates) and that higher ciliates gained, perhaps independently more than once, the ability to divide the macronucleus. Selective pressures that could have driven the evolution and macronuclear division and two plausible step-wise pathways for the evolution of macronuclear division are proposed. These hypotheses are relevant to our understanding of amitosis mechanisms, evolution of nuclear dimorphism, and phylogenetic classification of ciliates. PMID- 1908903 TI - Role of lipid metabolism in cell killing by calcium plus ionophore A23187. AB - Cultured fibroblasts treated with divalent cation ionophore A23187 in the presence of extracellular calcium provide a useful model system for studying mechanisms of cell death associated with elevated intracellular calcium concentrations. Cell death induced by A23187 plus calcium can be conveniently monitored as membrane permeabilization to Trypan blue dye. Because lipids are a major component of cell membranes and play an important role in determining membrane permeability, the present study was initiated to identify changes in cell lipid composition that occur during membrane permeabilization induced by calcium plus A23187. The percent label in each of the major structural lipids in biosynthetically labeled NIH3T3 fibroblasts changed less than 10% during the time course of membrane permeabilization. During the course of membrane permeabilization there was significantly increased label in lysophosphatidylinositol and lysophosphatidylcholine and reduced label in phosphatidylinositol 4,5-bisphosphate. The time course of these changes corresponded to that of the arachidonic acid release response stimulated by calcium plus A23187, not to the time course of membrane permeabilization, which occurs later. These observations are consistent with lipid metabolism induced by A23187 plus calcium playing only a possible regulatory or intermediatory role in membrane permeabilization, rather than causing direct permeabilization of the lipid phase of the membrane. PMID- 1908904 TI - Crystallization and preliminary X-ray crystallographic studies of CO-hemoglobin from the North Atlantic salmon (Salmo salar). AB - Purification of hemoglobin from North Atlantic salmon (Salmo salar) gave three different types. The CO-complexes of types I and III have been crystallized by the batch method at 4 degrees C from solutions 18% (w/v) in polyethylene glycol 2000, 50 mg/ml in hemoglobin and 0.05 M in phosphate buffer (pH 8.3). Orthorhombic crystals, space group P2(1)2(1)2(1), were obtained for both, with cell dimensions a = 53.9 A, b = 80.4 A, c = 132.4 A, and a = 58.7 A, b = 95.0 A, c = 107.4 A, for types I and III, respectively. PMID- 1908905 TI - Use of high coverage reference libraries of Drosophila melanogaster for relational data analysis. A step towards mapping and sequencing of the genome. AB - Three differently made, primary Drosophila cosmid libraries of 16-fold genome coverage have been generated. Also, a jumping library has been created by a new method that takes advantage of methylation differences between genomic DNA and vector. Thirdly, two cDNA libraries have been picked. All these libraries have been arrayed on high-density in situ filters, each containing 9216 clones. As a reference system, such filters are distributed and identified clones are provided. Single-copy probes have identified on average 1.4 cosmids per genome equivalent. Together with cytogenetically mapped yeast artificial chromosomes, the libraries are also being used for physically mapping the genome, mainly by oligonucleotide fingerprinting and pool hybridizations. cDNA clones are further examined by a partial sequencing analysis by oligomer hybridization. PMID- 1908906 TI - Polyamines and the calcium paradox in rat hearts. AB - Polyamine levels were measured by means of high-performance liquid chromatography in Langendorff-perfused rat hearts subjected to the calcium paradox protocol. The concentrations of putrescine, spermidine and spermine did not change significantly during calcium-free perfusion but decreased when calcium was readmitted. This decrease was due to membrane disruption and release of the polyamines into the coronary effluent. The sum of released and remaining spermidine exceeded the concentration of spermidine in control hearts, but, for spermine, this sum was lower than the control level. The addition of 0.5 mM EGTA to the calcium-free solution raised the myocardial concentrations of putrescine and spermidine and enhanced the net increase of spermidine on calcium repletion. DL-alpha-Difluoromethylornithine (DFMO) inhibited these increases and lowered the putrescine level during all perfusion stages. External polyamines had a negative inotropic effect and inhibited the loss of myoglobin on calcium repletion (order of effectiveness: spermine greater than spermine greater than putrescine). Inhibition of contractions by the combined action of verapamil and ryanodine or by potassium depolarization did not prevent myoglobin loss. External polyamines had no effect on high K/low Na contractures, which were mediated mainly by Na-Ca exchange. Calcium-free perfusion in the presence of 0.5 to 1 mM EGTA improved the membrane protection by polyamines or by diamines and analogues, like ornithine, 1,3-diaminopropane, or DFMO, which, in the absence of EGTA, gave no clear protection. It is concluded that calcium depletion and repletion influences myocardiaal polyamine concentrations by (1) membrane disruption and release of polyamines into the coronary effluent, and (2) probably by a stimulation of ornithine decarboxylase activity. The changes in polyamine concentrations do not seem to have any causal role in calcium overload and cell death. Exogenous polyamines protect against membrane damage. PMID- 1908908 TI - Is routine CT scanning necessary in the preoperative evaluation of patients undergoing carotid endarterectomy? AB - To evaluate the usefulness of CT scanning before carotid endarterectomy, a prospective study was performed on 469 consecutive patients considered for carotid endarterectomy during a 5-year period. All patients underwent carotid duplex scanning and CT scanning before carotid arteriography. Two hundred thirty seven patients (51%) had transient ischemic attacks, 109 (23%) had a prior stroke, and 122 (26%) were asymptomatic. Results of the CT scan were abnormal in 68 (62%) of the 109 patients with stroke. Fifty-one of the 360 patients (14%) without a clinical history of stroke had an abnormal CT scan outcome. Of patients with a stroke documented by CT scanning, 27 had lacunar infarcts, and 92 had cortical infarcts; these findings did not change surgical management in any patient. CT scanning did not reveal any unsuspected infarcts or tumors. Two hundred thirty carotid endarterectomies were performed on 206 patients. Forty seven patients (23%) in the operative group had abnormal CT scan findings, but the scan did not influence operative decisions or timing in any case. Seventy-two patients (27%) in the nonoperative group had abnormal CT scan results, but CT scan findings did not exclude any patient from arteriography or surgery. Three perioperative strokes (1.3%) occurred. CT scan findings did not correlate with postoperative neurologic complications. Cost of CT scanning was one-half million dollars in our study alone. Routine CT scanning is unnecessary before carotid endarterectomy and is not cost-effective. PMID- 1908907 TI - Myocardial dysfunction and norepinephrine release in the isolated rat heart injured by electrolysis-induced oxygen free radicals. AB - In the present investigation, we used electrolysis as a source of oxygen free radicals to test their possible role in norepinephrine release, as well as in the mechanism of cellular injury, cardiac dysfunction and arrhythmias. In the isolated rat heart perfused under constant pressure, according to the Langendorff technique, electrolysis of the Krebs-Henseleit solution (10 mA d.c. current for 1 min) produced myocardial irreversible dysfunction within 5 min. Fifteen minutes after electrolysis, significant falls in the left ventricular pressure (from 87.5 +/- 6.8 to 33.7 +/- 5.2 mmHg), dP/dt max (from 1230 +/- 90 to 375 +/- 59 mmHg/s), heart rate (from 287 +/- 18 to 119 +/- 13.5 beats/min) and coronary flow (from 14.8 +/- 9 to 3.4 +/- 1.7 ml/min) were observed, along with an increase in left ventricular end diastolic pressure from 10 to 50 +/- 3.5 mmHg (n = 8, P less than 0.01). AV conduction block and/or sinus bradycardia were noted in all preparations. An increase in norepinephrine washout from 298.5 +/- 84 at baseline to 610 +/- 110 pg/min/g 5 min after electrolysis was measured (n = 8, P less than 0.05) and a 44.8 +/- 9.2% and 35 +/- 7.5% reduction, respectively in right and left ventricular tissue norepinephrine content was also found at 30 min (n = 5, P less than 0.05). Pretreatment of the hearts 10 min before electrolysis and throughout the experimental period by superoxide dismutase (SOD; 100 U/ml), catalase (150 U/ml), a combination of SOD + catalase or mannitol (50 mM) partially blocked the deleterious effect of free radicals and permitted a functional recovery of 50 to 60%, mannitol being the more potent protective agent. Furthermore, these scavengers also significantly reduced norepinephrine washout.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1908909 TI - New preventive care guidelines may have more impact than predecessors. PMID- 1908910 TI - Reduced intravascular infection by antibiotic bonding. PMID- 1908911 TI - Structure-sensitivity relationship of anthracycline antibiotics to C7-reduction by redox enzymes. AB - About 30 antitumor anthracycline antibiotics were tested for their susceptibilities to reductive deglycosidation at C-7 catalyzed by rat liver microsomal NADPH-cytochrome P-450 reductase, xanthine oxidase, cytochrome C reductase and DT-diaphorase. Enzymatic activities to reduce the C-7 position of anthracycline antibiotics were similar among the four redox enzymes although a few exceptions were observed with DT-diaphorase. Among therapeutic use of anthracyclines, aclacinomycin A (ACM-A, aclarubicin) and daunomycin (daunorubicin) were found to be highly sensitive to the redox enzymes tested while adriamycin (ADM, doxorubicin) and THP-ADM (pirarubicin) were resistant to enzymatic reductive deglycosidation. When glycosidic and hydroxylated analogs of ACM-A were compared it was found that anthracyclines with smaller glycoside residues were more sensitive to the redox enzymes and the presence of hydroxyl groups on the aglycone moiety decreased the reductive deglycosidation activities. Thus, the aglycone, aklavinone, was most rapidly reduced to 7-deoxyaklavinone. 1 Hydroxy-, 2-hydroxy-, 11-hydroxy- and 1,11-dihydroaclacinomycins A were more resistant to the redox enzymes that ACM-A. Especially, 2-hydroxyaclacinomycins were completely insensitive to the enzymatic reduction. THP-ADM, 4'-substituted analog of ADM, was more resistant to the redox enzymes than ADM itself. These results show that the presence of a hydroxyl group, its position on aglycone, the presence of 4'-substituent on aminosugar and its length in the anthracycline molecule play important roles on the C-7 reduction by the redox enzymes. Relationship between reductive deglycosidation susceptibilities and cell-growth inhibitory activities of anthracycline antibiotics are also discussed. PMID- 1908912 TI - [An epidemiological study of hepatitis C virus infection in a local district in Japan]. AB - Mass screening of anti-HCV in Iyo city, Japan was performed. Sera from 136 subjects were tested for anti-HCV by ELISA (Ortho Diagnostic Inc.). Anti-HCV was positive in 13 subjects (9.6%). The familial study for anti-HCV revealed 2 persons positive for anti-HCV in 2 families each, while only 1 person was positive in each of the 8 other families. Two females were positive for both anti HCV and HBsAg, and all of their 3 children were negative for anti-HCV and positive for HBsAg. Positive rate of anti-HCV was higher in subjects who had a history of blood transfusion or "Chinese acupuncture" than that in those who did not. These results indicate that not only blood transfusion but also "Chinese acupuncture" and intrafamilial transmission are possible routes of HCV infection. The rate of vertical transmission of HCV is definitely lower than that of HBV. PMID- 1908913 TI - [Hepatitis C virus (HCV) infection in childhood]. AB - We studied the prevalence of hepatitis C virus (HCV) infection in childhood by determining HCV antibody (Ortho Diagnostic Systems, USA). Among patients with post-transfusion non-A, non-B hepatitis, anti-HCV was positive in 8 (72.7%) out of 11 patients. On the other hand, only 1 (25.0%) out of 4 patients of the children with acute non-A, non-B hepatitis, and only 1 (20.0%) out of 5 with chronic non-A, non-B hepatitis patients were positive for anti-HCV. Among the infants with non-A, non-B hepatitis, anti-HCV was positive in 3 (7.5%) out of 40 infants. To demonstrate mother-to-infant transmission of HCV, we examined 7 infants born to 4 anti-HCV positive mothers for their GPT values and anti-HCV. Liver dysfunction occurred in all the infants but one. And 1 infant was positive for anti-HCV. This infant with positive anti-HCV and liver dysfunction was considered to be a case of mother-to-infant transmission of HCV. And in the infants with liver dysfunction and negative anti-HCV, it was suggested that liver dysfunction occurred in association with HCV infection. PMID- 1908914 TI - [Evaluation of a new enzyme immunoassay method for determination of t-PA-PAI-1 complex]. AB - We evaluated a new enzyme immunoassay for determination of t-PA-PAI-1 complex (PAI-C) and studied the clinical utility of measuring PAI-C. This assay was performed by the capture/tag antibody technique using polystylene beads, in which the beads were coated with monoclonal antibody against PAI-1 and anti-t-PA polyclonal antibody was tagged (TDC-88, TEIJIN-LIMITED, Japan). The assay gave an excellent sensitivity with a detection limit of 0.1 ng/ml, and we were able to detect a trace amount of PAI-C in normal plasma. PAI-C in 6 volunteers showed significant daytime fluctuations. The normal value of PAI-C in plasma was below 13.8 ng/ml (n = 40). PAI-C levels in patients with accelerated fibrinolysis (n = 31) ranged from 2.9 to 66.4 ng/ml and 15 of them were outside the normal range. However, all of patients with DIC (n = 10) showed abnormally high PAI-C levels. In patients with accelerated fibrinolysis, PAI-C values correlated with t-PA antigen (r = 0.838), PAI-1 antigen (r = 0.519), ATIII activity (r = -0.669) (p less than 0.01) and D dimer levels (r = 0.391, p less than 0.05). However, PAI-C values did not correlate with plasminogen and alpha 2PI activity, alpha 2PI plasmin complex or the FDP-E level in these patients. Our data suggests that PAI C may be a new molecular marker that reflects t-PA release from endothelial cells and a useful indicator to study hypercoagulable states. PMID- 1908915 TI - [Two-color flow cytometric analysis on human peripheral blood T-lymphocytes using monoclonal antibody BM-1 directed to Le(Y) determinant structure]. AB - We developed a new assay method for the evaluation of Le(Y) antigen expression on human peripheral T-lymphocytes using the monoclonal antibodies BM-1, CD4 and CD8 by two-color flow cytometry. Le(Y) antigen expressed on human peripheral T lymphocytes was stained with fluorescein isothiocyanate (FITC)-labelled BM-1 (anti Le(Y) monoclonal antibody). Le(Y) positive cells were simultaneously stained with phycoerythrin (PE)-labelled CD4 or CD8, then analyzed by flow cytometer. Coefficients of variations in this double staining assays were 4.2% for BM-1 in CD4 and 5.3% for BM-1 in CD8, respectively. In 124 healthy volunteers 0.2-13.1% of CD4 and 2.5-12.5% of CD8 positive cells were BM-1 positive. Lymphocytes from 200 patients with acute or chronic viral hepatitis showed marked increase in BM-1 expression of CD8 positive cells during the acute phase and exacerbation of the disease. Moreover, BM-1 expression of CD4 cells was positively related with the course of the chronic hepatitis and the prognosis of each patients. Therefore, this new assay using BM-1 and CD4, CD8 monoclonal antibodies would reflect progression of viral hepatitis and its related immunological condition. PMID- 1908916 TI - [A case of esophageal mucosal bridge]. PMID- 1908917 TI - Comparison of cardiovascular effects of a novel class Ic antiarrhythmic agent, NIK-244, with those of flecainide in isolated canine heart preparations cross circulated with a donor dog. AB - To assess the cardiovascular effects of a new class I antiarrhythmic agent, NIK 244, and to compare them with those of flecainide, canine isolated, sinoatrial node, papillary muscle and atrioventricular node preparations cross-circulated with a donor dog were used. NIK-244 injected intraarterially into the isolated preparations showed dose-related negative chronotropic, negative inotropic, and coronary vasodilator effects, which are comparable to those of flecainide, and it also showed a dose-related negative dromotropic effect on both atrio-His (AH) and His-ventricular (HV) conduction. The prolongation of AH interval by NIK-244 was significantly more potent than that by flecainide, while that of the HV interval by NIK-244 was slightly more potent, but not significantly, compared with that by flecainide. NIK-244 administered intravenously into the donor dog showed bradycardic and depressor effects in both the donor dog and the cross-circulated sinus node and papillary muscle preparations, which are comparable to the effects of flecainide. Although the negative dromotropic effects of NIK-244 on both the donor dog heart and the cross-circulated atrioventricular node preparation started more slowly, they were more potent and longer-lasting than those of flecainide. Our results suggest that NIK-244 may be a more powerful and longer lasting antiarrhythmic agent than flecainide, since the antiarrhythmic action of class I drugs is considered to result from inhibition of the fast inward current, which is the most important depolarizing current responsible for the intraatrial and His-Purkinje-ventricular conduction. PMID- 1908918 TI - Microheterogeneity of the alpha subunits of G proteins in bovine brain clathrin coated vesicles. AB - Clathrin coated vesicles (CV) from bovine brain express the various alpha subunits of guanine nucleotide regulatory proteins (G-proteins): Go, Gi 1, 2, 3 and Gs. Western blot analysis using two different antisera revealed the presence of the 39-kDa Go alpha subunit in CV. Antisera RM/1, in turn, demonstrated the expression of the short (45 kDa) and long (52 kDa) form variants of the Gs alpha subunit. The analysis demonstrates that the heterogeneity of alpha subunits of G proteins in bovine brain tissue is also reflected in the CV transport organelles. PMID- 1908919 TI - Detection of G proteins in bovine brain clathrin coated vesicles with common alpha and beta subunits antibodies. AB - Clathrin coated vesicles (CV) from bovine brain were analyzed via Western blots for the presence of the alpha and beta subunits of guanine nucleotide regulatory proteins. The results with the common alpha antibody GA/1 revealed the presence of apparently undissociated G-protein subunits migrating at approximately 80 kDa. The predominant band was of about 39-41 kDa, with minor labeling observed in the 41-52 kDa range. Western blot analysis for G beta subunit(s) revealed the presence of a single band of about 35-36 kDa. PMID- 1908920 TI - Effect of HEBP (1-hydroxyethylidene-1,1-bisphosphonate) on experimental osteoporosis induced by ovariectomy in rats. AB - The present study was undertaken to test whether long term administration of HEBP could prevent the progress of bone loss induced by ovariectomy in rats. Administration of HEBP was started from day 111 after ovariectomy. The animals received subcutaneous injections of HEBP, at a dose of 0, 2, 4, or 8 mg/kg, every other day for 92 days. Tibiae, femora and incisor teeth were investigated by chemical analyses and by contact microradiography. Effects on calcium, phosphorus, and alkaline phosphatase activity in the plasma were also examined. Progress in the loss of bone density and ash content caused by ovariectomy was prevented by the administration of 2 mg/kg HEBP for 92 days and was partially prevented by the administration of 4 mg/kg. At a dose of 8 mg/kg, however, HEBP did not prevent the bone loss but, rather, potentiated it. These chemical findings were qualitatively confirmed by contact microradiography. A dose dependent inhibition was observed in the mineralization of incisor dentin. These results suggest that HEBP, at least at low dose levels in which the inhibition of mineralization is not predominant, has a potency to prevent the progress of bone loss induced by ovariectomy. At higher doses, however, this compound seems not to be effective, because of the severe inhibition of mineralization. PMID- 1908921 TI - [A case of Menkes' kinky hair disease with a renal calculus and diverticula of the bladder]. AB - Menkes' kinky hair disease is a poor prognostic congenital disease with X-linked recessive inheritance. This disease is clinically characterized by seizures, friable hair, growth failure, mental retardation and others. Recently it has been known that this disease is also characterized by multiple diverticula of the bladder and other urological abnormalities. A 6-year-old boy was diagnosed as having Menkes' kinky hair disease at another hospital several weeks after birth because of seizures, friable hair and low serum copper level. He voided by Crede's maneuver by the nurse because he could not void for himself. He was referred to our hospital for macrohematuria and micturition pain on October 8, 1989. Right renal staghorn calculus and multiple diverticula of the bladder were found by roentgenographic examination. He has been treated conservatively after discharge because of his poor condition. PMID- 1908922 TI - Neutrophil kinetics in the pulmonary microcirculation during acute inflammation. AB - The site of neutrophil interaction with the vasculature during acute lung inflammation is controversial, but has been suggested to occur in the alveolar capillaries, in contrast with its location in postcapillary venules in nonpulmonary tissues. We studied the kinetics of neutrophil accumulation and the site of neutrophil-vascular interaction in the lung by examining directly the behavior of fluorescein isothiocyanate-labeled canine neutrophils utilizing in vivo fluorescence videomicroscopy through a window inserted into the chest wall of anesthetized dogs. The administration of fragments of the fifth component of complement (C5f) into either the airway or pulmonary artery resulted in neutrophil sequestration almost exclusively in pulmonary capillaries. Kinetically, there was a shift in the distribution of neutrophil transit times resulting in a marked prolongation of median transit time. This response occurred within seconds after intravascular C5f and within 5 minutes after airway C5f and was maintained for at least 30 minutes. Ultrastructural studies after airway C5f showed neutrophils in various stages of migration through the alveolar-capillary membrane and more than 90% of these neutrophils were seen to migrate from capillary rather than from venular sites. These data indicate that pulmonary inflammation differs from inflammation in other vascular beds primarily in the site of neutrophil localization and migration. This fundamental difference in the inflammatory response may serve to localize the inflammatory response to the alveolus, and (since cells were retained singly), indicates the inability of leukoaggregation adequately to explain the findings. Leukocyte accumulation in the lung may thus occur through alterations in the balance between delivery of neutrophils to the lung and the transit time of these cells across the capillary bed. PMID- 1908924 TI - Animal models for the study of fetal tissue repair. AB - Recent experimental and clinical evidence suggests that the fetus responds to injury in a fashion fundamentally different from that of the adult. Acute inflammation is almost always absent, hyaluronic acid is a prominent component of the wound matrix, and collagen is deposited in a scarless manner. Using a variety of animal models and techniques, numerous investigators have begun to analyze the constituents of the fetal wound healing process in an attempt to understand the control mechanisms that endow the fetus with unique healing abilities. Since scarring and fibrosis dominate some diseases in almost every medical specialty, the ultimate clinical aim is to delineate the biological principles of fetal wound healing and then apply them to modulate adult wound healing problems. PMID- 1908923 TI - Interferon gamma increases sensitivity to endotoxin. AB - Interferon-gamma (IFN-gamma) has been proposed for use following severe trauma to reverse depressed macrophage (M phi) function and thereby reduce infection, sepsis, and subsequent multiple organ failure syndrome (MOFS). However, an excessive inflammatory response by M phi s and other components of the inflammatory cascade is thought to be central to the underlying pathophysiology of MOFS. Endotoxin (LPS) has been implicated as a principal mediator of sepsis induced MOFS by stimulating M phi s and leukocytes (WBC). This study addresses the following question: Does IFN-gamma predispose normal rabbits to a pathophysiologic response to LPS infusion? Four groups of New Zealand White rabbits (n = 6, each group) were prepared for measurement of cardiac output, arterial pressure, arterial PO2, and WBC counts over a 6-hr period. Group I (control) was instrumented alone, Group II (LPS alone) was given a subclinical dose of 1.0 micrograms/kg of Escherichia coli LPS iv, Group III (IFN-gamma alone) was given recombinant rabbit IFN-gamma (5.0 micrograms/kg subcutaneous) for 3 days prior to preparation for measurements, and Group IV (IFN-gamma + LPS) received 3 days of IFN-gamma followed by LPS. One hour prior to sacrifice 5.0 microCi of 125I-albumin was given and bronchoalveolar lavage was performed at death to determine the lavage/plasma 125I ratio as an index of pulmonary permeability. The results indicate that IFN + LPS animals had significant decreases in cardiac output, PO2, and WBC counts, and increased lavage/plasma ratio of 125I-albumin when compared to all other groups (P less than 0.05 by ANOVA, t test). Neither LPS alone nor IFN-gamma alone had a significant effect on measured variables.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1908925 TI - Urinary PGE2 in rats with chronic partial unilateral ureteral obstruction. AB - Urinary prostaglandin E2 (PGE2) was measured in Munich-Wistar rats with surgically created chronic partial unilateral ureteral obstruction (UUO). Mean values of bladder urine PGE2 were higher in sham than in UUO (24.5 +/- 14.4 vs 12.9 +/- 8.2 ng/mg creatinine, respectively, P less than 0.05). Following diuresis, both ureters were cannulated and urine was collected. PGE2 excretion was increased in sham (66.5 +/- 34.4 and 70.1 +/- 44.5 ng/mg creatinine, left and right, respectively). But in UUO, the obstructed kidney excreted less PGE2 than the contralateral kidney (32.1 +/- 6.0 vs 62.3 +/- 40.4 ng/mg creatinine, obstructed vs contralateral, respectively, P = 0.08). PGE2 synthesis was then determined in separated renal medullary and cortical slices. Renal medullary slices from kidneys with severe obstruction synthesized less PGE2 than the contralateral unobstructed side (3.30 +/- 1.22 vs 10.52 +/- 3.23 ng/mg wet wt-30 min, respectively, P less than 0.05) and failed to respond to arachidonic acid stimulation with any significant increase in PGE2 synthesis (3.30 +/- 1.22 vs 4.47 +/- 1.04 ng/mg wet wt-30 min, baseline vs stimulated). In contrast, contralateral unobstructed kidney slices responded with a significant increase in PGE2 synthesis (10.52 +/- 3.23 vs 21.10 +/- 2.50 ng/mg wet wt-30 min, baseline vs stimulated, P less than 0.05). We conclude that chronic partial UUO in the Munich Wistar rats resulted in significantly less PGE2 elaboration. PMID- 1908926 TI - Effect of intravenous or intragastric nutrients on food intake in rats. AB - A series of experiments were performed to determine which components of total parenteral nutrition (TPN) reduce spontaneous food intake (SFI) and to what degree. In Experiment 1, rats were infused with TPN (15% dextrose + 5% fat + 4.3% amino acid) or with one of its three components given independently at the final concentration of TPN for 3 days via an intravenous (iv) catheter. Each solution, at 3 ml/hr, provided a different amount of calories (TPN = 85, dextrose = 37, fat = 36, and amino acid = 12 kcal/day), representing about 120, 50, 50, and 20% of the rat's spontaneous caloric intake, respectively. TPN, dextrose, and fat significantly reduced SFI compared to the infusion of normal saline; however, amino acid failed to reduce SFI. Experiment 2 was carried out to investigate the relative contributions that pre- and postabsorptive mechanisms make in the regulation of SFI. Each rat in four different groups was infused with one of four isocaloric nutrient solutions through an iv catheter and a gastrostomy (ig) for separated periods of time. Nutrient solutions at 3 ml/hr provided each 32 kcal/day (50% of requirements): 13% dextrose, 4.5% fat, 11.4% amino acid, and a mixture (6.4% dextrose + 1.6% fat + 1.7% amino acid). Each solution, either iv or ig, reduced SFI compared to normal saline infused via the same route. However, neither the route of administration nor the nature of different nutrients caused significant differences in SFI reduction. PMID- 1908927 TI - Effect of oxygenation and consequent pH changes on the efficacy of St. Thomas' Hospital cardioplegic solution. AB - The hypothesis tested is that shifts in pH, induced when a cardioplegic solution is oxygenated, can be detrimental. We added either 100% nitrogen, 95% nitrogen and 5% carbon dioxide, 100% oxygen, or 95% oxygen and 5% carbon dioxide to the cardioplegic solution (St. Thomas' Hospital No. 2 plus glucose 11 mmol/L), and determined postischemic recovery of isolated rat hearts after 3 hours of 10 degrees C cardioplegic protected ischemia. Hearts were arrested and reinfused every 30 minutes throughout the ischemic period with cardioplegic solution. When 5% carbon dioxide was added to nitrogen, the pH of the cardioplegic solution decreased from 9.1 (100% nitrogen) to 7.0 (95% nitrogen: 5% carbon dioxide), a change associated with improved postischemic functional recovery. Aortic output improved from 52.3% +/- 2.7% to 63.9% +/- 2.8%, p less than 0.05, and cardiac output from 60.8% +/- 3.6% to 75.4% +/- 3.3%, p less than 0.01. This improvement was associated with diminished efflux of lactate during ischemia but increased postischemic release of lactate dehydrogenase. When nitrogen was replaced with oxygen, the addition of 5% carbon dioxide resulted in a similar decrease of pH, which again was associated with improved postischemic functional recovery. Aortic output improved from 66.3% +/- 2.8% (100% oxygen) to 88.9% +/- 3.7% (95% oxygen: 5% carbon dioxide), p less than 0.005, and cardiac output from 75.3% +/- 4.1% to 88.9% +/- 2.4%, p less than 0.01. The efflux of lactate during ischemia and the postischemic release of lactate dehydrogenase were similar in both groups. Furthermore, provision of additional oxygen with perfluorocarbons in an electrolyte solution identical to the St. Thomas' Hospital plus glucose solution and oxygenated with 95% oxygen: 5% carbon dioxide conferred no extra protection. In conclusion, the St. Thomas' Hospital No. 2 plus glucose cardioplegic solution should be oxygenated but with 95% oxygen: 5% carbon dioxide and not 100% oxygen because of the additive effect of a relatively "acidotic" pH. PMID- 1908928 TI - Continuous arterial and venous blood gas monitoring during cardiopulmonary bypass. AB - A new monitoring technique, based on optical fluorescence chemistry, allows continuous monitoring of all blood gas variables during cardiopulmonary bypass. To evaluate the clinical performance of this monitor, we drew 220 arterial and 216 venous blood samples from 15 patients, and simultaneous blood gas values displayed by the monitor were compared with standard laboratory measurements. The continuous monitor predicted laboratory values with varying degrees of accuracy. (R2 values by linear regression: arterial oxygen tension 0.86, venous oxygen tension 0.36, arterial carbon dioxide tension 0.58, venous carbon dioxide tension 0.72, arterial pH 0.53, venous pH 0.58; pH 0.53, venous pH 0.58; p less than 0.0001). Monitor values of arterial oxygen tension overestimated laboratory values (bias = + 43.5 mm Hg), but the laboratory reference method likely underestimated true arterial oxygen tension in the high range achieved on bypass. Monitoring of venous oxygen tension was imprecise (precision = +/- 6.51 mmHg), regardless of whether stable conditions existed during the sampling period. Monitoring of carbon dioxide tension and pH showed small bias (carbon dioxide tension within 2 mm Hg, pH within 0.03) and good precision (carbon dioxide tension within 3 mm Hg, pH within 0.03). With the development of unstable conditions on bypass, monitor arterial oxygen tension values showed a changing relationship to corresponding laboratory values. In conclusion, arterial and venous carbon dioxide tension and pH monitoring provide acceptably accurate alternatives to laboratory measurement of these variables during cardiopulmonary bypass. Arterial oxygen tension monitoring accurately indicates changes in oxygen tension in the arterial oxygen tension range typically produced during extracorporeal circulation. Oxygen tension monitoring in the venous oxygen tension range is too imprecise for clinical decision-making purposes. PMID- 1908929 TI - Double-labelling with rhodamine beads and biocytin: a technique for studying corticospinal and other projection neurons in vitro. AB - Corticospinal neurons retrogradely labelled with rhodamine-labelled latex microspheres (RLMs) in vivo were studied intracellularly in a slice preparation up to 13 months later with electrodes containing biocytin. The physiological properties of these double-labelled corticospinal neurons were indistinguishable from those of comparable neurons which were impaled with biocytin-containing electrodes without prior RLM-labelling, and neurons studied with potassium acetate-filled electrodes in similar areas. Thus, neither labelling with RLMs nor injection of biocytin affected neuronal properties. This important advantage of RLMs makes them suitable for prelabelling projection neurons in vivo for subsequent studies that take advantage of the versatility of a brain slice preparation. In addition to its lack of effects on neuronal properties, intracellular labelling with biocytin also provides high-quality morphological details ideal for anatomical analysis. The compatibility of retrograde labelling with RLMs and intracellular staining with biocytin make this a useful combined technique for tracking electrophysiological and anatomical changes in identified projection neurons over time. PMID- 1908930 TI - Headspace gas chromatography of volatile lipid peroxidation products from human red blood cell membranes. AB - An improved headspace capillary gas chromatographic (GC) method was developed to measure the oxidative susceptibility of human red blood cell (RBC) membranes. This method analyzed volatile peroxidation products of both n-6 (hexanal and pentane) and n-3 (propanal) polyunsaturated fatty acids. Oxidative susceptibility tests were standardized by incubating in a sealed 10-mL headspace bottle 0.25 or 1 mL of human RBC membrane in 40 mM phosphate buffer for 1 hr at 37 degrees C with a mixture of Fe++, ascorbic acid and H2O2. Sodium dodecyl sulfate increased significantly the amount of hexanal measured by headspace GC. By this standard headspace method, in one series of red blood cell membranes (RBCM) samples a four fold variation in oxidative susceptibility was observed in RBCM from blood freshly drawn from six healthy subjects. In another series of RBCM samples a sixteen-fold variation in oxidative susceptibility was noted in frozen RBCM from blood freshly drawn from five healthy subjects. Correlation between hexanal formation and polyunsaturated fatty acids (PUFA) depletion provided good evidence that under these standard conditions hexanal is exclusively derived from the oxidation of arachidonic acid. Hydroperoxides of arachidonic acid are more readily formed and decomposed than those of linoleic acid in the presence of Fe++, ascorbic acid and H2O2 to produce hexanal as the main product that can be readily analyzed by headspace GC. This method may provide a useful tool to study susceptibility toward lipid peroxidative damage in human RBC membranes. PMID- 1908932 TI - Magnetic resonance imaging of leiomyomata uteri: assessing therapy with the gonadotropin-releasing hormone agonist leuprolide. AB - Two cases are reported in which MRI was used to monitor the preoperative response of leiomyomata uteri to gonadotropin releasing hormone agonist therapy. The uterus was measured in the cephalocaudad, anterior-posterior, and transverse planes by MRI images. All uterine dimensions decreased in size after leuprolide therapy. One patient ultimately chose leuprolide therapy alone for control of her symptoms while a second patient had four myomas surgically removed after leuprolide therapy. MRI proved to be a good modality to monitor response to leuprolide therapy and assist in the management of these patients. PMID- 1908931 TI - Methods for the systematic investigation of gastrointestinal contrast media for MRI: evaluation of intestinal distribution by radiographic monitoring. AB - Comparison of the effectiveness of various gastrointestinal (GI) contrast agents for magnetic resonance (MR) imaging is often complicated by varying amounts intraluminal filling with the orally administered agents. To achieve more uniform and reproducible imaging results with GI contrast agents for MR imaging (GICMR), we evaluated a radiographic method for monitoring intraluminal filling and distribution. Solutions of Mn-DPDP (2 mM), to which a small amount of barium sulfate (6 wt/vol%) was added, were administered orally to dogs. Gastric emptying and small bowel transit were monitored fluoroscopically. MR imaging was performed either 1) at a fixed time after administration of the contrast agent or 2) at a variable interval when the contrast agent was observed fluoroscopically to be in the terminal ileum. When initiation of MR imaging was guided by fluoroscopic monitoring of intestinal contrast distribution, uniform and reproducible intestinal contrast enhancement by GICMR was achieved. However, when MR imaging was performed at a fixed time interval after oral administration, non-uniform and variable GI visualization was obtained, and this corresponded to the variable intestinal distribution observed fluoroscopically. We conclude that reproducible intestinal filling with orally administered contrast agents can be accomplished with a radiographic monitoring technique, and this promotes more consistent GI visualization on MR images. Such standardized and reproducible methods are necessary for studies in which the effectiveness of GI contrast media for MR imaging is evaluated and compared. PMID- 1908933 TI - Plexiform neurofibroma of the pelvis: CT and MRI findings. AB - We present a case of plexiform neurofibroma of the pelvis in a patient with neurofibromatosis using magnetic resonance imaging (MRI) with computed tomography (CT) correlation. We discovered an extensive pelvic mass with a slightly greater signal intensity than muscle in T1-weighted images and a marked increased signal intensity in T2-weighted images. Multiple hypointense septations were identified throughout the tumor, particularly in the T2-weighted images. The MR appearance of pelvic plexiform neurofibroma is identical to those found in spinal and paraspinal locations. In the presence of an extensive pelvic mass in a patient with neurofibromatosis, MRI is recommended in evaluating and diagnosing plexiform neurofibroma. Since the MRI appearance of this tumor is characteristic, other lesions can possibly be ruled out. In addition, MRI's multiplanar capability is ideally suited to demonstrate the extension of these large tumors. PMID- 1908934 TI - Evaluation of medical technologies: a generalized ROC analysis. AB - The author describes a new methodology to solve medical decision problems involving a choice between alternatives under conditions of risk and uncertainty when imperfect empirical information from diagnostic technologies is available. The main new concept is the generalized ROC (GROC) curve, which extends considerably the scope of analysis of the traditional ROC curve as well as the threshold approach to medical decision making. Both techniques become special cases of the new general approach. The author shows how to apply the technique and derive comprehensive clinical guidelines to solve the medical decision problem involving one patient in the most general situation. The larger problem of evaluating the performances of diagnostic technologies for a population of patients with varying prior probabilities of disease is then addressed. A new measure of performance is proposed that goes beyond the well-accepted area under the ROC curve index. This measure is used to compare different technologies for a population of patients, and a new methodology is proposed to carry out such comparisons. PMID- 1908935 TI - [The use of the helium-neon laser for preventing acute radiation reactions of the skin during neutron therapy of head and neck cancer]. PMID- 1908936 TI - Diffusion/microcirculation MRI in the rat brain. AB - The CO2 fraction of an anesthetized rat's breathing mixture was changed (from 0 to 10%) to attempt to change the brain microcirculation and observe these changes in diffusion measurements of the neural tissue. Brain apparent diffusion coefficients were measured to be (0.71 +/- 0.01) X 10(-3) mm2/s before sacrifice and (0.39 +/- 0.01) X 10(-3) mm2/s after sacrifice. Multiple diffusion components were observed, consistent with flowing material, but the extra components did not increase with increased CO2. It is proposed that the additional components may be due to extracellular, extravascular water such as CSF. PMID- 1908938 TI - Effects of tannic acid on spontaneous and induced somatic mutations in Drosophila melanogaster. AB - The effects of tannic acid (TA) alone and in combination with direct acting chemical genotoxins and gamma-radiation were investigated in Somatic Mutation and Recombination Tests (SMARTs) using Drosophila melanogaster. Treatment with TA alone (2.5-15 mmol/l) resulted in a moderate but dose dependent induction of mosaic spots in males and females, indicating that the compound possesses mutagenic and recombinogenic activity. When TA (10 mmol/l) was given simultaneously with MMS, 4-NQO and cis-DDP, a potentiating effect on their mutagenicity was observed in males whereas in females no such increase was measured. The frequency of 4-NQO induced mosaic spots in males was raised more than threefold in presence of TA, for MMS and cis-DDP the enhancement was approximately 2-fold; with gamma-radiation no synergistic effect occurred. The different response in the two sexes indicates that TA preferentially induces gene mutations and deletions but has no enhancing effect on the number of mosaic spots which are formed as a consequence of recombinogenic events. PMID- 1908939 TI - [Listeria monocytogenes contamination of raw milk from different regions of Anatolia and pasteurized milk sold in Ankara]. AB - In this study 77 raw milk samples from different regions of Anatolia and 22 pasteurized milk samples sold in Ankara were investigated for isolation of L. monocytogenes. For the isolation of Listeria, each sample was plated directly onto McBride's Listeria Agar (MLA) and on the other hand four processing methods (2 long cold enrichment and 2 shortened warm enrichment procedures, followed by plating) were used. Listeria colonies on MLA medium were examined by the Henry Method of oblique lighting. Suspected colonies from MLA were subjected to biochemical tests to confirm identity. 14 samples (18.2%) of all examined samples raw milk were determined to be positive for Listeria monocytogenes. We found that Tryptose Phosphate Broth enrichment procedure gave significantly better results than others and allows L. monocytogenes isolation from milk most frequently. All of tested pasteurized milk samples were negative for L. monocytogenes. PMID- 1908937 TI - Multinuclear MR investigation of the metabolic response of the murine RIF-1 tumor to 5-fluorouracil chemotherapy. AB - The metabolic response of the RIF-1 tumor to 5-fluorouracil (a single dose of 260 mg 5FU/kg, ip) was monitored in 10 mice using 19F and 31P MR spectroscopy. 19F MRS revealed a continuous drop in tumor 5FU level and an increase in the fluoronucleotide (Fnuc) signal to a plateau value of 50% of the initial 5FU level, during the first 2 h after chemotherapy. Although the 31P MR spectra of the tumors showed no significant initial changes, the total level of MR visible tumor phosphate decreased and tumor pH increased during the subsequent days. The changes in phosphate metabolism and tumor pH did not correlate with the detected fluorine levels or tumor response. However, the pretreatment Pi level, the plateau Fnuc level, and the 5FU induced decrease in tumor volume showed significant correlation. This indicates that both 19F and 31P MR spectroscopy have potential for predicting response to 5FU chemotherapy. PMID- 1908940 TI - Isolation of two antigens from the culture filtrates of Mycobacterium tuberculosis and their applications in the laboratory diagnosis of the tuberculous meningitis. AB - Two antigens were isolated from the culture filtrates of H37Ra Mycobacterium tuberculosis by immunoabsorbent affinity chromatography, M. tuberculosis antigen 5 and immunoabsorbent affinity column-purified antigen (IAP). The potential application of these two mycobacterial antigens in the laboratory diagnosis of tuberculous meningitis was evaluated by indirect enzyme-linked immunoabsorbent assay in cerebrospinal fluid specimens. IAP antigen was more sensitive than antigen 5, although antigen 5 was more specific than IAP antigen in detecting tuberculous aetiology. Technical aspects of immunoabsorbent affinity chromatography have been highlighted in this study. PMID- 1908941 TI - [Molecular biological study of the vaccinia virus genome. IV. The late nonstructural 36K protein of vaccinia virus is vitally important]. AB - Two genetics markers: the herpes simplex virus thymidine kinase and Escherichia coli beta-galactosidase genes were inserted into the 36K protein gene of vaccinia virus located in a HindIII-P DNA fragment. An unstability of recombinant viruses with Lac(+)-phenotype were discovered. A mechanism of viruses unstable variants formation was proposed, it was confirmed by the results of hybridisation analyses of virus recombinant genomes. The importance of a late nonstructural 36K protein gene for virus reproduction was demonstrated. PMID- 1908942 TI - [DNA from human lymphocytes contains a sequence, homologous to immunoglobulin gene kappa]. AB - DNA released by human lymphocytes and hyman blood plasma DNA were examined by the electrophoresis, electron microscopy and Southern blot hybridization. The data obtained suggested that DNA released by lymphocytes contains covalently closed circular molecules. By the technique of the Southern blot analysis it was shown that DNA released by lymphocytes and human blood plasma DNA contain discretely sized molecules homologous to the C kappa fragment of the human Ig gene. PMID- 1908943 TI - Productive interactions between B and natural killer cells. AB - In this report, we have established that natural killer (NK) cells can increase IgG2a secretion by B lymphocytes as well as alter the distribution of the remaining immunoglobulin isotypes. The effect of NK cells on B cell differentiation is similar to that obtained by the direct addition of recombinant interferon-gamma (IFN-gamma) and, therefore, most likely results from the elaboration of IFN-gamma by NK cells, this is a clear demonstration that NK cells can regulate cell function(s) via a mechanism other than cytotoxicity. In addition, we have shown that the induction of NK cells by B lymphocytes requires close interactions between the two cell types. Further, while only low-density B lymphocytes activated in vivo are effective inducers of NK cells, high-density, resting B cells can be rendered effective by preactivation with either interleukin-4 or anti-mu. PMID- 1908944 TI - Kinetochore analysis of micronuclei allows insights into the actions of colcemid and mitomycin C. AB - We have induced micronuclei in two strains of diploid human fibroblasts with a known aneugen, colcemid, and a known clastogen, mitomycin C. Using immunofluorescence to detect the presence of kinetochores in micronuclei, we were able to demonstrate a 26.8-fold increase in fluorescence-positive micronuclei (aneuploidy) in colcemid-treated cells. However, colcemid also induced an increase in kinetochore-negative micronuclei. Our findings support previous reports that suggest colcemid may induce chromosome breakage in addition to its major aneugenic effect. The frequency of kinetochore-negative micronuclei (chromosome breakage) in mitomycin C-treated cells rose an average of 7.9-fold in the two test strains, a clear reflection of its clastogenic action. However, a 4 fold increase in the kinetochore-positive fraction was seen. We conclude that the fibroblast micronucleus assay, coupled with kinetochore immunofluorescence, provides a useful screening approach for genotoxic agents. The delineation of the precise mechanism by which an agent perturbs the rates of chromosomal breakage or lag may require more detailed analysis. PMID- 1908945 TI - DNA methylation alters the pattern of spontaneous mutation in Escherichia coli cells (mutD) defective in DNA polymerase III proofreading. AB - We have shown previously that dam mutants of Escherichia coli have a weak mutator phenotype which generates mostly transition mutations in the P22 mnt gene. In contrast, in mutD5 cells, which have a strong mutator phenotype, transversion mutations were the most prevalent. A dam-16 mutD5 strain, defective in both DNA polymerase III associated-proofreading and Dam-directed mismatch repair exhibits a strong mutator phenotype but, surprisingly, its mutation spectrum is similar to that of the dam rather than the mutD parent. The most likely explanation is that Dam-directed mismatch repair in the mutD5 strain corrects most of the potential transition mutations (therefore yielding transversions) in the newly synthesised strand. When the dam-16 allele is present together with mutD5 a reduced efficiency of repair as well as loss of strand discrimination and misdirected repair results in the appearance of transition mutations at high frequency. PMID- 1908946 TI - Decreased clastogenicity of dinitropyrenes in Chinese hamster lung (CHL) subclone cells with low NADPH-cytochrome P-450 reductase activity. AB - Clastogenic potentials of 1,3-, 1,6- and 1,8-dinitropyrenes (DNPs) were compared between Chinese hamster lung (CHL) cells and its subclone MM1 cells, which were recently isolated as menadione-resistant cells after treatment with MNNG. NADPH cytochrome P-450 reductase activity of the MM1 cells decreased to 50% of that in the parental CHL cells. All 3 DNPs induced chromosomal aberrations without exogenous metabolic activation systems in the CHL cells. 1,6- and 1,8-DNP showed equivalent clastogenic potency: the maximum frequency of cells with chromosomal aberrations was about 50% for both chemicals. The clastogenic potential of 1,3 DNP was lower than that of 1,6- and 1,8-DNP: the maximum frequency of aberrant cells was 10%. In the MM1 cells, in contrast, the frequencies of aberrant cells decreased to about 30% of those observed for the parental CHL cells after treatment with 1,6- and 1,8-DNP, and to the same level as that of the concurrent control after treatment with 1,3-DNP. These results suggest a possibility that the reduced clastogenic effect of 3 DNPs in MM1 cells may correlate with the reduced activity of NADPH-cytochrome P-450 reductase which is thought to contribute to the metabolic conversion of these DNPs to their clastogenic forms in the CHL cells. PMID- 1908948 TI - Sweet success, but an acid aftertaste? PMID- 1908947 TI - Influence of beta-myrcene on sister-chromatid exchanges induced by mutagens in V79 and HTC cells. AB - The influence of beta-myrcene (MC) on sister-chromatid exchanges (SCE) in V79 cells induced by 4 S9 mix-activated indirect mutagens was studied. The mutagens used were cyclophosphamide (CP), benzo[a]pyrene (BP), aflatoxin B1 (AFB) and 9,10 dimethyl-1,2-benz[a]anthracene (DMBA). MC effectively inhibited SCEs induced by CP and AFB in a dose-dependent manner, but it had no effect on SCE induction by BP and DMBA. MC also reduced CP-induced SCE frequencies in a hepatic tumor cell line (HTC). These cells are metabolically competent and activate CP into its biologically active metabolites. Our results support the suggestion that MC modulates the genotoxicity of indirect-acting mutagens by inhibiting certain forms of the cytochrome P-450 enzymes required for activation of premutagens like CP and AFB. PMID- 1908949 TI - Splenic hemorrhage after tissue plasminogen activator for acute myocardial infarction. PMID- 1908950 TI - Neurobiology. Curious cortical change. PMID- 1908951 TI - Bcl-2 maintains B cell memory. AB - The number of lymphocytes in an animal is remarkably constant despite antigen driven proliferation and a high rate of B-cell lymphopoiesis. This reflects the relatively brief lifespan of many newly generated B cells and argues for a well regulated death mechanism. Even so, a secondary immune response can be generated years after a primary exposure to antigen. Antigen that might restimulate B cells persists for extended periods on follicular dendritic cells in the light zone of germinal centres. Antigen-binding B cells have also been found months after the end of obvious cell division. The precise signal that enables certain B cells to emerge as long-term surviving memory cells is unknown. Bcl-2, an inner mitochondrial membrane protein, blocks programmed cell death in B cells. We report here that this proto-oncogene maintains immune responsiveness. Transgenic mice overproducing Bcl-2 have a long-term persistence of immunoglobulin-secreting cells and an extended lifetime for memory B cells. PMID- 1908953 TI - Relationship of primary structure to functional properties of the cytotoxin protein from Pseudomonas aeruginosa. AB - Deletion mutants of plasmid pSN3 carrying the Pseudomonas aeruginosa cytotoxin gene were prepared and expression in Escherichia coli of proteins with different molecular weights has been proved by Western blot. In addition, through PCR amplification of the cytotoxin gene and ligation into the vector, a single nucleotide change leading to an amino acid exchange from histidine to arginine has been constructed. The activities of the mutants were tested by binding of 125I-cytotoxin to rabbit erythrocyte ghosts and swelling of human granulocytes, showing that the cytotoxin activity is dependent on at least three different domains. Amino acids 12-20 from the C-terminus might be very important for proteolytic activation of protoxin to toxin. PMID- 1908954 TI - [Antiepileptic chemoprevention after skull injury]. PMID- 1908952 TI - Spasmolytic effect of cromakalim in dog coronary artery in vitro. AB - Isometric force development was measured in isolated ring segments of dog left anterior descending coronary artery to K+ (10-70 mM), U-46619 (0.3-30 nM), endothelin-1 (0.1-30 nM), 5-HT (0.1-30 microM) and angiotensin-II (0.1-30 nM). Compared with the maximum tissue response to a K+ depolarizing solution (100%) there was a marked variation in the maximum response to each spasmogen: K+ (111%), U-46619 (85%), endothelin-1 (48%), 5-HT (49%) and angiotensin-II (15%). In arteries pretreated with cromakalim (0.3 - 10 microM) the maximum response to all constrictor agents (with the exception of K+) was reduced but the potency was unaffected. Maximum responses to angiotensin-II and 5-HT were affected at concentrations approximately threefold lower than those to endothelin-1 and U 46619. Removal of the endothelium increased the maximum response caused by 5-HT and reduced the potency of cromakalim in inhibiting this contraction. Glyceryl trinitrate and sodium nitroprusside were 100-1000 times more potent than cromakalim although they produced qualitatively similar effects. Cromakalim is an effective spasmolytic against a number of vasoconstrictors in the dog coronary artery. No marked spasmogen selectivity could be identified for cromakalim that was not shown by glyceryl trinitrate or sodium nitroprusside. PMID- 1908957 TI - Induction of HSP70 mRNA after transient ischemia in gerbil brain. AB - Heat shock protein (HSP) plays an important role in stress responses of cells. Inductions of HSP70 mRNA, amyloid precursor protein (APP) mRNA, and tubulin mRNA within hippocampal CA1 and parietal cortex in gerbil brains were examined at 1 h to 7 days after 10 min of bilateral common carotid artery occlusion using Northern blot analyses. In contrast to the induction of HSP70 mRNA, no induction was observed in APP mRNA or tubulin mRNA. Regional differences in the induction of HSP70 mRNA were found. CA1 cells produced less amount of HSP70 mRNA than cortical cells at 8 h after the transient ischemia. Transient global ischemia is known to result in the selective neuronal death of hippocampal CA1 cells days after reperfusion. Our results suggest that the regional difference in the induction of HSP70 mRNA may relate to the regional difference of the vulnerability of neuronal cells after transient ischemia. PMID- 1908955 TI - Lipid fluidity and composition of the erythrocyte membrane from healthy dogs and Labrador retrievers with hereditary muscular dystrophy. AB - Erythrocyte membranes and their liposomes were prepared from clinically normal dogs and Labrador retrievers with hereditary muscular dystrophy. The "static" and "dynamic" components of fluidity of each membrane were then assessed by steady state fluorescence polarization techniques using limiting hindered fluorescence anisotropy and order parameter values of 1,6-diphenyl-1,3,5-hexatriene (DPH) and fluorescence anisotropy values of DL-2-(9-anthroyl)-stearic acid and DL-12-(9 anthroyl)-stearic acid, respectively. Membrane lipids were extracted and analyzed by thin-layer chromatography and gas chromatography. The results of these studies demonstrated that the lipid fluidity of erythrocyte membranes, and their liposomes, prepared from dystrophic dogs were found to possess significantly lower "static and dynamic components of fluidity" than control counterparts. Analysis of the composition of membranes from dystrophic dogs revealed a higher ratio of saturated fatty acyl chain/unsaturated chains (w/w) and lower double bond index. Alterations in the fatty acid composition such as decrease in levels of linoleic (18:2) and arachidonic (20:4) acids and increase in palmitic (16:0) and stearic (18:0) acids were also observed in the membranes of dystrophic animals. These associated fatty acyl alterations could explain, at least in part, the differences in membrane fluidity between dystrophic and control dogs. PMID- 1908958 TI - Selective induction of Kunitz-type protease inhibitor domain-containing amyloid precursor protein mRNA after persistent focal ischemia in rat cerebral cortex. AB - An induction of amyloid precursor protein (APP) mRNA was examined in a middle cerebral artery occlusion model of rats using Northern blot analyses. The level of tubulin mRNA was measured as an internal standard. With persistent focal ischemia, APP mRNA species which contain a Kunitz-type protease inhibitor (KPI) domain were induced in the rat cerebral cortex from 1 to 21 days after the insult with a maximum at 4 days, while total amounts of APP mRNA did not change. No change was observed in the level of tubulin mRNA. These results suggest a selective role of APP species which contain the KPI domain in focal cerebral ischemia. PMID- 1908956 TI - Oxygen toxicity in the nervous tissue: comparison of the antioxidant defense of rat brain and sciatic nerve. AB - Nervous tissue, central and peripheral, is, as any other, subject to variations in oxygen tension, and to the attack of different xenobiotics; these situations may promote the generation of activated oxygen species of free radical character. Results are presented showing that the content of total glutathione (GSH) in brain is 10-fold that found in the sciatic nerve of the rat (2620 vs. 261 nmol/g wet weight, respectively). The existence of a relatively high superoxide dismutase activity in peripheral nervous tissue, when compared with brain or liver, in combination with the DT-diaphorase activity detected in the sciatic nerve might represent an effective defense mechanism against quinone toxicity, as is also discussed. Nervous tissue, both central and peripheral lack Se independent GSH peroxidase activity. Finally, the activities of other glutathione related enzymes studied in the sciatic nerve are very low, when compared with the central nervous tissue, thus suggesting a higher susceptibility of peripheral tissue to oxidative stress damage, since GSH concentration and/or any GSH-related enzymatic activities, e.g. GSH peroxidase or glutathione disulfide reductase, might become limiting. PMID- 1908959 TI - Effects of intra-axonal injection of Ca2+ buffers on evoked release and on facilitation in the crayfish neuromuscular junction. AB - Ca2+ buffers were injected into the excitatory axon of the crayfish opener muscle. The magnitude and time course of evoked release and of facilitation were measured. EGTA (on-rate about 10(6) M-1S-1) had no effect on evoked release but reduced facilitation. BAPTA and nitr-5, buffers with similar Kd's but faster on rates, reduced both evoked release and facilitation. However, these buffers had no effect on the time course of evoked release. These results show that fast Ca2+ buffers reduce the Ca2+ transient associated with evoked release and also the level of residual Ca2+ involved in facilitation. However, Ca2+ buffering is not the mechanism which controls the time course of release. PMID- 1908960 TI - Autoradiographic study of the cellular localization of [3H]glibenclamide binding sites in the rat hippocampus. AB - [3H]Glibenclamide, a potent ATP-sensitive K+ channel blocker, is a specific ligand for the identification of the sulfonylureas receptors which are closely related to ATP-sensitive K+ channels. In order to determine the pre- or postsynaptic localization of these receptors in the rat hippocampus, we studied the effects of selective kainate or colchicine-induced lesions on the regional distribution of [3H]glibenclamide binding. A decreased binding was found in the following conditions: in CA3, after destruction of the mossy fiber terminals but not of the CA3 cells; in CA1, after destruction of the CA1 cells but not of the Schaffer collaterals; in the fascia dentata, after destruction of the granule cells. These results suggest that glibenclamide binding sites are mainly localized on the mossy fibers in CA3, and on the granular and pyramidal neurons in the fascia dentata and CA1, respectively. PMID- 1908961 TI - Different regulations of dopaminergic (D1) receptors and neurotensinergic binding sites in the rat prefrontal cortex. AB - The effects of the destruction of mixed dopamine/neurotensin (DA/NT) meso cortical neurons were investigated by studying the development of denervation supersensitivity of DA (D1) and NT cortical post-synaptic binding sites using respectively [3H]SCH 23390 and [125I]NT as ligands. These neurons were destroyed bilaterally either by injection of 6-hydroxydopamine (6-OHDA) or by an electrolytic coagulation made in the ventral tegmental area (VTA). Five weeks later, both [3H]SCH 23390 and [125I]NT bindings were analysed by quantitative autoradiography on each lesioned animal and on corresponding controls. The chemical lesions of the VTA induced an increase in the density of the cortical NT binding sites but did not affect D1 binding sites. On the contrary, electrolytic lesions induced an increase in D1 binding sites and no change in NT binding sites. One possible explanation of these differences may be that, since chemical lesions of the VTA destroy noradrenergic (NA) ascending pathways while electrolytic lesions spare the cortical NA innervation, the observed modifications of D1 and NT cortical binding sites following their presynaptic denervation are dependent on the presence (increase in D1 receptors) or the absence (increase in NT binding sites) of the cortical NA innervation. PMID- 1908962 TI - Concentrations of tyrosine, L-dihydroxyphenylalanine, dopamine, and 3-O methyldopa in the cerebrospinal fluid of Parkinson's disease. AB - We determined the concentrations of tyrosine, L-3,4-dihydroxyphenylalanine (DOPA), dopamine (DA), and 3-O-methyldopa (3-OMD) in the cerebrospinal fluid (CSF) of parkinsonian patients and elevated potential interactions between the substances. We found a significant increase in tyrosine, and a significant decrease in DOPA, DA, and 3-OMD. We also found that for a given concentration of DOPA, DA and 3-OMD were proportional. In addition, the ratio of DA to 3-OMD was significantly shifted in favor of DA in parkinsonian patients. PMID- 1908963 TI - Small GTP-binding proteins in human neuroblastoma cell lines. AB - The presence of small G proteins was investigated by [gamma-35S]GTP-binding in 3 human neuroblastoma cell lines. IMR-32, SK-N-BE and SH-SY5Y, before and after treatment with differentiating agents (dibutyryl-cAMP, 5-bromodeoxyuridine or retinoic acid) which induce the appearance of secretory organelles. One major component of about 24 kDa and 3 minor components of smaller Mr were found to bind specifically [gamma-35S]GTP in all 3 cell lines already before differentiation. Differentiation did not affect the expression of small G proteins in IMR-32 cells and only modestly affected it in the other two cell lines. The possibility that the expression of small G proteins in neuroblastoma cells is not coupled with the assembly of secretory organelles is discussed. PMID- 1908964 TI - Structure of Lisch nodules in neurofibromatosis type 1. AB - Postmortem examination of the eyes of a patient with neurofibromatosis Type I was performed by light and electronmicroscopy. Lisch nodules were examined and found to consist of a condensation of spindle cells on the anterior iris surface. When nodules were pigmented an underlying stromal naevus was present. Lisch nodules are confirmed as being of melanocytic origin. PMID- 1908965 TI - A serological comparison of complement fixation reactions using Brucella abortus and B. melitensis antigens in B. abortus infected cattle. AB - Brucella abortus and B. melitensis antigens were used in parallel on the National Standard Brucella abortus antiserum and on field sera coming from cattle where practically exclusively B. abortus biotypes 1 and 2 have been isolated over the last 11 years. With the National Standard serum the titres to B. melitensis were consistently lower than those to B. abortus antigen. Most were 1 dilution (twofold) lower. Although a similar trend was seen with the field sera, there were 7/346 sera which had twofold or higher titres to B. melitensis antigen. Although this may be due to the vagaries of the test it also warrants closer investigation of the animals concerned to see whether M-antigen predominant Brucella biotypes are possibly present. The use of the dual antigens could identify herds which are infected only with A-antigen predominant brucellae but would not be reliable for classifying individual animals. PMID- 1908966 TI - Otolaryngology and head and neck surgery in the twenty-first century. PMID- 1908967 TI - Intraoperative facial nerve monitoring: prognostic aspects during acoustic tumor removal. AB - Intraoperative facial nerve monitoring with electrical stimulation (IFNMES) has become an integral part of acoustic tumor surgery. We reviewed the records of fifty-six patients who underwent translabyrinthine acoustic tumor removal with IFNMES. There was excellent correlation between intraoperative facial nerve activity and immediate postoperative facial nerve function (24 hours after surgery and at hospital discharge). Our data would suggest that patients who exhibit less than 500 microvolts of ongoing EMG activity during surgery, and who yield at least a 500-microvolt contraction when stimulated with 0.05 milliamps at the brainstem after tumor removal, can expect an excellent immediate facial nerve result (grade I or II). PMID- 1908968 TI - Longitudinal followup of patients with Meniere's disease. AB - The etiology, pathophysiology, and natural history of Meniere's syndrome are poorly understood. The reported studies have had inadequate followup or insufficient numbers of patients to allow conclusions about the natural history. Our study group was 119 patients who had the classic symptom complex of episodic vertigo, tinnitus, and hearing loss in the year 1970. After initial review of these charts, follow-up information was obtained by questionnaire, telephone interview, chart review, or repeat examination, when possible, both in 1983 and in 1988, for a total followup of 18 years. In the patients with followups of at least 14 years, vertiginous episodes had disappeared completely in 50% of patients and somewhat resolved in 28%; hearing was absent in 48% and worse in 21%. Surprisingly, 43% of patients underwent surgery at some point for control of vertigo. Bilateral disease was present initially in 13% and developed subsequently in 45% of patients. Other areas reviewed included the efficacy of long-term medical treatment, frequency and severity of vertiginous attacks, and contralateral ear symptoms. PMID- 1908969 TI - Blindness resulting from orbital complications of sinusitis. AB - Loss of vision remains a potential complication of orbital infection. Appropriate evaluation and management of the patient with signs and symptoms of orbital inflammation may prevent progression to blindness. Evaluation of patients with orbital inflammation from sinusitis includes a comprehensive clinical examination and radiographic studies. Clinical examination should test for changes in visual acuity, pupillary reactivity, and extraocular motion. Computerized tomography (CT) has facilitated the diagnosis of orbital infections and aids in diagnosis. However, CT can be misleading in patients with acute orbital infections and should not be relied on to determine the need for surgical intervention. We reviewed the records of all patients admitted to Parkland Memorial Hospital from 1978 to 1988 with orbital complications resulting from sinusitis. Four of 159 patients in this group had permanent blindness. The presence of an abscess, which was ultimately found at surgical exploration, was not diagnosed by CT in any of these four patients. Clinical examination remains the most important indicator for surgical intervention in patients with orbital complications of sinusitis. We present our findings and give guidelines for surgical intervention in patients with orbital infections resulting from sinusitis. PMID- 1908970 TI - Perilymphatic fistula: analysis of free amino acids in middle ear microaspirates. AB - High-performance liquid chromatography was used to determine 19 free amino acid concentrations in perilymph, serum/plasma, and red blood cell intracellular fluid. Significant differences were found between perilymph and these fluids. Free amino acid analysis was then used to quantitatively analyze middle ear microaspirates in order to test the hypothesis that perilymph is a potential source of clear fluid in perilymphatic fistulas (PLF). Fourteen unknown samples from patients with visually identified PLF, including patients with no identifiable otic capsule defect, were studied. Six samples on amino acid pattern analysis were correlated most similarly with perilymph (rrho greater than 0.95). Four of these six samples were scored on the basis of quantitative amino acid values as similar to perilymph. However, three samples of clear fluid were more similar to serum/plasma than to perilymph on both amino acid pattern and quantitative amino acid score analysis. These results objectively suggest perilymph as a potential source of clear fluid in some patients with a diagnosis of PLF. Not all clear fluid observed in the middle ear, however, is potentially perilymph. PMID- 1908971 TI - Ossifying fibroma of the mid-face and paranasal sinuses: diagnostic and therapeutic considerations. AB - Ossifying fibroma is benign, usually slow-growing tumor that may behave in an unpredictably aggressive fashion. Most of these unusual tumors affect the mandible. Their behavior in the mid-face and paranasal sinuses is not well documented. In our review of the subject, and of the cases presented, it appears that these lesions behave more aggressively than their mandibular counterparts. A more aggressive approach may be more beneficial than expectant observation or curettage in the initial management of this neoplasm. PMID- 1908972 TI - Epiglottic laryngoplasty after hemilaryngectomy for glottic cancer. AB - Epiglottic laryngoplasty is technically feasible as a one-stage procedure with excellent functional results. Although the Kambic-Sedlacek-Tucker (K-S-T) technique of glottic reconstruction offers early extubation with an adequate airway, a subsequent wide neoglottis may increase the chance of aspiration and a poor voice. To better restore the laryngeal functions of closure and phonation, we made some modifications on the original K-S-T technique as follows: (1) One of the lateral margins of the epiglottis with the aryepiglottic fold is sutured to the arytenoid region of the cricoid rather than a thyroid cartilage remnant. A neo-arytenoid is formed. (2) The other lateral margin of the epiglottis with the aryepiglottic fold is sutured to the cut edge of the false and true cord instead of a thyroid ala remnant. Therefore both margins of the epiglottis with the aryepiglottic folds are lowered as much as possible to the level of the glottis. A new pseudocord is formed. (3) A cartilage cut is made at the anterior aspect of the epiglottis, leaving its laryngeal surface of mucoperichondrial intact. A new anterior commissure with a sharp angle is shaped by this maneuver. Nineteen hemilaryngectomies with modified epiglottic laryngoplasty have been performed by members of the Department of Otolaryngology of Guangxi Medical College since 1984. Results in this series are fairly good and indicate that the modified epiglottic laryngoplasty is effective in enhancing functional results in terms of respiration, deglutition, and phonation. PMID- 1908973 TI - Facial nerve monitoring in acoustic tumor surgery. AB - Anatomic and functional preservation of the facial nerve during acoustic tumor surgery remains a primary goal. Intraoperative electromyographic facial nerve monitoring with auditory feedback has enabled the surgeon to more readily achieve this goal. We compared a group of monitored translabyrinthine acoustic tumor removals (N = 89) to a similar unmonitored group (N = 155) in regard to facial nerve function. Function was assessed immediately postoperatively, at time of discharge, and at 1 year postoperatively using the House six-point scale. Results were grouped as satisfactory, intermediate, or poor and were analyzed by tumor size. Facial nerve results were better at all time intervals in the monitored groups, although the difference was not statistically significant at the 1-year interval. There was no difference between monitored and unmonitored patients in the subgroups with tumors smaller than 2.5 cm in diameter. This study supports the usefulness of intraoperative facial nerve monitoring in improving facial nerve results, particularly in larger tumors. PMID- 1908974 TI - Hypoglossal-facial nerve interpositional-jump graft for facial reanimation without tongue atrophy. AB - The hemitongue paralysis that occurs as a result of a classic hypoglossal-facial nerve crossover procedure can result in profound functional deficits in speech, mastication, and swallowing. The procedure is not an option in patients with bilateral facial paralysis or those at risk for combined cranial nerve deficits. To address some of the drawbacks and limitations of this classic procedure, we developed the hypoglossal-facial nerve interpositional jump graft (12-7 jump graft) procedure. This procedure involves interposing a nerve graft between a partially severed but functionally intact twelfth cranial nerve and the degenerated seventh cranial nerve, and is often combined with other reanimation procedures. To date, we have performed 33 12-7 jump graft procedures in 30 patients (three were treated for bilateral facial paralysis); this report describes the procedure and its indications, and details the results of 23 procedures performed in 20 patients for whom 24-month follow-up data are available. Twelfth nerve deficits occurred in only three patients in this report. Recovery of facial function began between 3 and 24 months postoperatively. Facial tone and symmetry were achieved in every patient, no patient had significant mass movement, and 13 patients (two of whom were treated for bilateral facial paralysis) had excellent and three had superb restoration of facial movement. These results show the 12-7 jump graft to be a valuable adjunct for facial reanimation in selected patients. PMID- 1908975 TI - Facial nerve stimulation with cochlear implantation. VA Cooperative Study Group on Cochlear Implantation. AB - The course of the facial nerve may place it within the current field generated by an activated cochlear implant to produce incidental facial movement. We investigated the presence of facial nerve stimulation associated with cochlear implants in the VA Cooperative Study of Advanced Cochlear implants. Twelve of 82 patients enrolled in this study demonstrated facial nerve stimulation within 2 years of implant activation. Facial nerve stimulation in six patients with multiple channel implants (Nucleus or ineraid devices) either resolved spontaneously (n = 2), or was eliminated by deactivating basal (n = 2) or apical (n = 2) electrodes. Two of six patients with single-channel electrodes (3 M/Vienna devices) demonstrated facial nerve stimulation that resolved spontaneously (n = 2), resolved with lowering current output (n = 2), or was refractory to processor adjustment (n = 2). Intraoperative assessment in one of the refractory cases indicated that facial nerve stimulation resulted from current spread through the modiolus to activate the facial nerve. A variety of factors, including implant design, stimulus parameters, and local tissue impedances, may interact to produce incidental facial stimulation. Low-impedance pathways between the scala tympani and the modiolus may deserve increased recognition as an interactive factor in cochlear implant performance. PMID- 1908976 TI - Laser cordectomy for T1 glottic carcinoma: a 10-year experience and videostroboscopic findings. AB - Fifty-three patients underwent laser cordectomy for T1 glottic squamous cell carcinoma between January 1980 and December 1989--sixteen after having undergone unsuccessful radiation and thirty-seven who had no previous treatment. There was a 51% five-year cure rate in the irradiated group vs. 62% in the nonirradiated group. Extension of tumor to the anterior commissure resulted in a higher failure rate. Patients experienced an overall 5-year cure rate of 98% after surgical or radiation salvage of unsuccessful laser cordectomies. Six patients had preoperative and postoperative videostrobolaryngoscopy. The most common postoperative problem with voice was a breathiness that did not resolve in any of the patients. All patients had absent or moderately reduced amplitude and mucosal wave patterns and imcomplete glottic closure proportional to the amount of cordal tissue removed. Despite it seemingly poor results in carefully selected patients, laser cordectomy is still indicated without compromising the ultimate oncologic results. Advantages over radiation therapy or conservation laryngeal surgery include a short treatment time, requiring only an outpatient surgical procedure at the time of the initial diagnostic and/or staging laryngoscopy, and the avoidance of potential radiation side effects or surgical complications. However, patients should be advised the possibility of persistent postoperative breathy dysphonia, in addition to the possibility of further treatment to effect a long term cure. PMID- 1908977 TI - Radiotherapy of advanced laryngeal cancer using three small fractions daily. AB - Since 1983, we have treated advanced (UICC stages III and IV) squamous carcinomas of the larynx by primary radiotherapy, using three small fractions a day, 3-4 h interfraction interval, 5 days per week. The early patients received doses per fraction of 1.5 Gy, and a total dose of approximately 70 Gy, given as a split course over 6 to 7 weeks. While overall tumor control and laryngeal preservation was good, a number of severe late radiation reactions were seen. The schedule was then modified, with a reduction in the fraction size to 1.1 Gy, the total dose to 60 Gy, and the overall time to 4 weeks, with omission of the mid-treatment "split." Since 1986, we have treated 26 patients in this way. Acute reactions are brisk, but rapidly healing. Loco-regional control was achieved in 22 patients, only one of whom has relapsed to date, in a solitary node, salvaged by radical neck dissection. Four have died of uncontrolled loco-regional malignancy, and three of intercurrent disease while in clinical remission. No serious late morbidity has been observed in surviving patients, and vocal quality is good in the majority. These results suggest that this hyperfractionated and accelerated radiotherapy schedule may offer an acceptable nonsurgical, voice-preserving treatment for advanced laryngeal carcinoma; it can be used in a normally working radiotherapy department. PMID- 1908978 TI - Microsubglottoscopy: an expansion of operative microlaryngoscopy. AB - The development of the adult subglottiscope has facilitated expansion of the indications for operative microlaryngoscopy to include surgery in the subglottic region of the larynx, as well as in the upper cervical trachea. A set of microlaryngeal instruments with an elongated shaft has been developed to support the use of the subglottiscope in the adult patient population. During the 18 month period from January 1, 1988, through June 30, 1989, sixteen adult patients with subglottic or upper cervical tracheal pathology were operated on a total of twenty-three times, using the adult subglottiscope to facilitate exposure and treatment. The patients' pathologic conditions included subglottic stenosis, subglottic granuloma, subglottic extension of laryngeal hemangioma and papilloma, and suprastomal granuloma. Two selected cases are presented to highlight indications for the use of this instrument. We have found the exposure of these subglottic and upper cervical tracheal lesions, using the binocular, microlaryngeal approach facilitated by the adult subglottiscope, to be improved over that obtained with existing microlaryngoscopes or conventional tracheoscopes. PMID- 1908979 TI - Successful treatment of selected cases of abductor spasmodic dysphonia using botulinum toxin injection. AB - Ten patients with abductor spasmodic dysphonia, who exhibited spasmodic bursts and heightened activity of the cricothyroid muscle during speech, were selected for participation. Between 5 and 20 U of botulinum toxin type A were injected into both right and left cricothyroid muscles. Six patients benefited substantially, whereas four did not. Acoustic analyses of voice patterns showed similar changes to the clinical impressions. Significant group improvements were found in sentence duration while selected patients improved in the proportion of their speech that was voiced and the duration of their voiceless consonants. Those patients with abductor spasmodic dysphonia and other muscle abnormalities in addition to the cricothyroid and with constant breathiness did not benefit. PMID- 1908980 TI - Sphenoethmoid sinus mucocele presenting with amenorrhea and galactorrhea. PMID- 1908982 TI - False-positive MR imaging in the diagnosis of acoustic neurinomas. PMID- 1908981 TI - Life-threatening hemangioma arising from the parotid gland. PMID- 1908983 TI - Neurofibromatosis type I--a rare case resulting in conductive hearing loss. AB - Notwithstanding the many similarities, there are important differences between NF1 and NF2. NF1-related neurofibromas, which can number in the hundreds, can occur all over the body. Unique clinical situations, such as the case described here, can occur that test the ingenuity of the physician. Once the presenting problem has been ameliorated, genetic counseling is imperative in this common and at times devastating genetic disease. PMID- 1908984 TI - Otogenic cavernous sinus thrombosis. PMID- 1908985 TI - Congenital gustatory facial flushing. PMID- 1908986 TI - Upper airway obstruction and craniofacial morphology. AB - Otolaryngologists are being asked with increasing frequency to assess adequacy of the upper airway and to treat upper airway obstructive problems in orthodontic patients. The incentive has been provided by recent studies that purport to relate upper airway obstruction to dental and craniomorphologic changes. It is hypothesized that prolonged oral respiration during critical growth periods in children initiates a sequence of events that commonly results in dental and skeletal changes. In the chronic mouth-breather excessive molar tooth eruption is almost a constant feature, causing a clockwise rotation of the growing mandible, with a disproportional increase in anterior lower vertical face height. Such increases in anterior lower vertical face height are often associated with retrognathia and open bites. Low tongue posture seen with oral respiration impedes the lateral expansion and anterior development of the maxilla. Otolaryngologists have the ability to objectively and accurately assess upper airway patency. Rhinometric assessment before and after application of topical nasal decongestant, in conjunction with clinical examination, provides valuable information regarding upper airway patency and the cause of any existing obstructive pathologic condition. Studies should be designed carefully to control the numerous variables that have an impact on the growing face of a young child so that meaningful data can be obtained in our own field regarding this challenging topic. PMID- 1908987 TI - Angle-tipped Baron suction tubes. AB - Modified Baron no. 3 suctions angled at the tips have been found to be valuable during otologic surgery. The 3-mm length has been found most helpful and its use is recommended. PMID- 1908988 TI - Torticollis in children. AB - Torticollis is a common clinical sign that is found in a variety of disorders. Childhood torticollis differs from the adult form in that congenital types are common and many frequently encountered disorders found in adults are unusual. Pediatric torticollis related to otolaryngologic conditions is reviewed, and three illustrative cases are presented. PMID- 1908989 TI - The infectious and hematologic otolaryngic complications of myelosuppressive cancer chemotherapy. AB - The otolaryngologist-head and neck surgeon is frequently consulted to evaluate patients before the administration of myelosuppressive cancer chemotherapy. Fifty consecutive patients treated at the University of Pennsylvania Oncology Center were studied before and during chemotherapy for adult leukemia or bone marrow transplantation. Otolaryngic history, physical examination, radiographic studies, and hematologic surveys were analyzed for the duration of therapy in an attempt to identify risk factors for infectious and hematologic otolaryngic complications. Two-thirds of the patient studied experienced untoward effects that required the further attention of an otolaryngologist-head and neck surgeon. The various complications and associated correlations with the study parameters before and during chemotherapy are discussed. PMID- 1908990 TI - Selective chemical vestibulectomy: preliminary results with human application. AB - The involved membranous labyrinth of patients with medically intractable Meniere's disease is being accessed by means of a fenestration of the bony horizontal semicircular canal in preparation for the application of a 125 or 250 mcg flake of solid streptomycin. Sensory information originating in the affected vestibular end organ is selectively blocked from reaching the central nervous system. This uniformly results in the rapid elimination of vertiginous symptoms, and at these calculated doses yields preservation of (or in some cases improvement in) preoperative cochlear thresholds. The rationale for this procedure, as detailed in earlier investigations of animals, will be briefly reviewed before highlighting our preliminary results in adult clinical trials. PMID- 1908991 TI - Fibromuscular dysplasia of the vertebral artery: an unusual cause of pulsatile tinnitus. PMID- 1908992 TI - Meningitis as a result of a cochlear implant: case report. PMID- 1908993 TI - Delayed extrusion of the nucleus multichannel cochlear implant. PMID- 1908995 TI - Pitfalls in the evaluation of Lyme disease. PMID- 1908994 TI - Evoked otoacoustic emissions in differential diagnosis: a case report. PMID- 1908996 TI - Salivary cysts following parotid duct translocation for sialorrhea. PMID- 1908997 TI - Sternoclavicular arthritis and manual pressure necrosis: two potential complications of tracheoesophageal puncture. PMID- 1908998 TI - Management of drooling. PMID- 1908999 TI - Science is for the moment and truth is forever. PMID- 1909000 TI - Avoidance of nasopharyngeal incompetence in uvulopalatopharyngoplasty. PMID- 1909001 TI - Surgical anatomy of the lateral nasal wall. PMID- 1909002 TI - Postoperative bleeding incidence after local anesthesia tonsillectomies. PMID- 1909003 TI - Myospherulosis of the paranasal sinuses. PMID- 1909004 TI - Method for allocation of hearing handicap. PMID- 1909006 TI - Determining side of vestibular dysfunction with rotatory chair testing. AB - Determining side of vestibular lesion remains a challenging task during neurotologic investigations, particularly if auditory lateralizing signs are absent. Traditionally, absent or decreased caloric response has been regarded as evidence of unilateral vestibular deficit. But, the inability of the chair test to detect side of lesion has been generally accepted because rotation stimulates both end organs. A retrospective study postulated and tested a hypothesis that low-frequency asymmetry of sinusoidal harmonic acceleration (SHA) testing can determine side of lesion when phase is abnormal. The present prospective, double blind study was designed to further test the retrospective study hypothesis. Results showed that SHA asymmetry detects side of unilateral vestibular deficit when phase is abnormal in 97% of cases. PMID- 1909005 TI - Repair of a cerebrospinal fluid perilymph fistula primarily through the middle ear and secondarily by occluding the cochlear aqueduct. AB - A 35-year-old man had a 5-year history of fluctuating hearing loss in his only hearing ear. History and diagnostic tests indicated a perilymph fistula, a diagnosis subsequently confirmed by exploration. Primary and secondary repairs temporarily ameliorated symptoms. A spinal fluid to middle ear fluid pathway was identified by radioactive tracer. A patent cochlear aqueduct indicated on computed tomography scan was found and repaired through a posterior cranial fossa approach. Hearing was preserved, remaining relatively stable during the 2-year follow-up period. PMID- 1909007 TI - Fourth branchial pouch sinus: diagnosis and treatment. AB - The fourth branchial pouch sinus (FBPS) is a rare translaryngeal anomaly with diverse manifestations, including neonatal stridor and recurrent deep neck infection. Review of the world literature reveals 23 reports of sinuses consistent with fourth pouch origin. We present two additional cases, including the only example of a right-sided FBPS. Retrograde excision, beginning at the piriform apex, ensures complete removal of the tract and protection of the recurrent nerve. The posterior border of the thyroid ala must be resected or retracted for adequate exposure. Failure to remove the translaryngeal portion of the tract almost guarantees recurrence. PMID- 1909008 TI - Perilymphatic fistula: surgical experience in the United States. AB - One survey sent to 6953 individual otolaryngologic practices and 106 departments of otolaryngology at teaching hospitals in the United States, and a more limited survey of 75 patients operated on for perilymphatic fistula (PLF) at the House Ear Institute, addressed aspects of managing PLF: surgical incidence, reliability of diagnostic test, preoperative observations, and disability after surgery. Of surgeons sampled, 93% estimated incidence of PLF surgery to be less than or equal to 1 per 1000 otolaryngologic outpatient visits. The most reliable diagnostic indicators were history, symptomatology, and tympanometric and electronystagmographic fistula tests. About 72% of surgeons reported less than 4 weeks' average delay before surgery. Most surgeons and patients (greater than or equal to 70%) rated length of disability before return to work, exposure to noise, travel by airplane, swimming, and heavy lifting, at several weeks to several months. Diving was the most restricted activity. Results suggest that incidence of surgery and disability with PFL in the United States is very limited. PMID- 1909009 TI - The role of preoperative CT scans in staging external auditory meatus carcinoma: radiologic-pathologic correlation study. AB - Survival is related to the pathologic extent of tumor in external auditory meatus (EAM) carcinoma. This study assesses the validity of preoperative CT scans in staging EAM carcinoma. The accuracy of staging EAM carcinoma with preoperative CT scans was evaluated by comparing radiography and histopathology. Patients who received preoperative CT scan were selected from a retrospective series of 35 temporal bone resections for EAM squamous cell carcinoma. The CT scans were systematically reviewed for tumor involvement in 12 anatomic areas. The histopathology slides for the corresponding patients were reviewed according to the same criteria. CT scan findings accurately diagnosed the extent of tumor involvement identified during histopathologic examination. These tumors demonstrated the capacity to spread along existing anatomic pathways as well as direct bone erosion. We conclude that preoperative CT scans accurately stage EAM squamous cell carcinoma. PMID- 1909010 TI - Prognostic factors in advanced head and neck cancer patients undergoing multimodality therapy. AB - A retrospective analysis was performed to investigate potential prognostic factors for complete remission to neoadjuvant chemotherapy and overall survival in patients with previously untreated stage III and stage IV head and neck cancer. Eighty consecutive patients were treated in one of two studies investigating three or four courses of neoadjuvant chemotherapy. Before local therapy and surgery and/or radiotherapy, 29% attained a complete remission. No strong significant and independent predictor of complete remission was identified. Only nodal stage (N) was found moderately associated with complete remission (p = 0.06). Node-negative patients had higher remission rates. Less important predictors were tumor stage (T) and site of disease; nasopharyngeal patients had superior remission rates (56%). With a median followup of 45 months and estimated 3-year survival rate of 38% (median 23.7 months), individual factors predictive of survival included pretherapy weight loss, performance status, alcohol use, pretherapy serum albumin level, site of disease, and N stage. In multivariate testing weight loss was identified as the strongest independent predictor of survival (p less than 0.0001) and surpassed other health status measures, such as performance status and serum albumin level. In addition, N stage (p = 0.019) and alcohol use (p = 0.017) were found to be predictive. A cross-classification by N stage and weight loss revealed risk groups with distinctly different prognoses, which may be useful for design and analysis in future trials. PMID- 1909011 TI - Myringoplasty in children. AB - This series examines the results of myringoplasty in children using the overlay technique. Controversy still surrounds the issue of proper timing of surgery on the basis of preoperative assessment of tubal function. Results of this technique in children, using contralateral ear status as the primary predictor of success, found an overall success rate of 78%. Age appears to be a significant factor because children 10 years old and younger were found to have a higher incidence of surgical failures. PMID- 1909012 TI - Vagal body tumors. AB - Six cases of vagal body tumor are reviewed. All first presented as painless neck masses with normal cranial nerve function. Otologic symptoms were infrequent, occurring only with temporal bone involvement. In true vagal paragangliomas, cranial nerve and auditory function is usually preserved until there is extensive disease of the skull base. Tumor progression after radiotherapy was documented in four patients, three of whom were treated with 4500 cGy or more. One patient was found to have regional lymph node metastases. The six patients had a total of 10 head and neck paragangliomas, illustrating the high incidence of synchronous and metachronous lesions. Because of the high incidence of multiple lesions, these tumors threaten lower cranial nerves bilaterally in many instances. Because cranial nerve function is preserved until late, and because vagal and accessory nerve paralysis is usually unavoidable with resection, we advocate conservative treatment in selected cases. It may be reasonable to postpone surgery until cranial nerve impairment becomes evident or other vital structures are threatened. PMID- 1909013 TI - Oncocytic metaplasia of the pharynx. AB - Oncocytic metaplasia of the pharynx has been infrequently described, with only two previous cases in the literature. With the advent of panendoscopy during the last decade, however, a better understanding of this histopathologic diagnosis is desirable. Thirty-three cases are reviewed, with thirty occurring in the nasopharynx. This was most commonly discovered as an unrelated finding during endoscopic evaluation of a head and neck mass or malignancy in twenty-two patients, either histologically after random biopsy or after biopsy of small but visible lesions. An additional eight cases manifested otitis media or eustachian tube dysfunction. The histology, terminology, and benign clinical nature of these lesions are discussed. PMID- 1909014 TI - Retropharyngeal space infection: changing trends. AB - Retropharyngeal space infection, now a rare entity since the introduction of modern antibiotic chemotherapy, has traditionally been described to occur in children less than 4 years of age with suppurative disorders of the ear, nose, and throat. Recent reports suggest a changing trend in the epidemiology, bacteriology, diagnostic imaging, treatment, and clinical course of this entity. However, the medical literature concerning this topic over the last two decades has consisted mainly of case reports. We reviewed eight cases of retropharyngeal space infection at our institutions over a 15-year period, representing one of the largest clinical series of its kind in the last 20 years. Patient ages ranged from 3 months to 41 years. Findings of these cases and 13 cases from similar reports obtained by a MEDLINE computer search of the recent literature were analyzed. Results show a trend toward occurrence in older age groups, polymicrobial infections, successful use of CT scan as a diagnostic modality, and fewer patients requiring incision and drainage. These findings will be discussed and contrasted to conventional wisdom. PMID- 1909016 TI - [In vitro activity of cefuroxime against Moraxella (Branhamella) catarrhalis]. AB - Minimal inhibitory concentrations of cefuroxime were determined by an agar dilution procedure and compared with erythromycin and four other beta-lactam antibiotics (amoxycillin, amoxycillin + clavulanate, cefadroxil, cefaclor) on 76 strains of Moraxella (Branhamella) catarrhalis. Sixty four of them produced a beta-lactamase. Results show that the beta-lactamase of Moraxella (Branhamella) catarrhalis abrogates the activity of amoxycillin (MIC 90% = 4 mg/l) meanwhile the combination of amoxycillin-clavulanate is inhibitory at low concentration (MIC 90% = 0.25 mg/l). There are no difference in MICs between strains producing or not producing beta-lactamase with erythromycin (MIC 90% = 0.25 mg/l). All the strains evaluated in this investigation, producing or not producing beta lactamase have MIC 90% less than or equal to 2 mg/l for cefuroxime lower than those obtained for the two other cephalosporins. PMID- 1909015 TI - [In vitro activity of beta-lactam antibiotics in combination with sulbactam against enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter. Results of a multicenter study]. AB - The in vitro antimicrobial activity of ticarcillin (TICAR), mezlocillin (MEZLO), piperacillin (PIPER), cefoperazone (CPZ), cefotaxime (CTX) and ceftazidime (CAZ), alone and in combination with 8 micrograms/ml of sulbactam (SULB), was studied by agar dilution against TICAR resistant strains isolated in 8 hospitals over a period of 3 months in 1989 (747 enterobacteria, 110 Ps. aeruginosa and 48 Acinetobacter sp.). SULB did not modify the activity of beta-lactam antibiotics against Ps. aeruginosa. The 6 beta-lactam antibiotics SULB combinations were only active for 27% of Acinetobacter SULB sensitive. SULB restored the activity of: MEZLO, PIPER, CPZ in Enterobacteria producing a penicillinase; PIPER, CTX and CAZ in Enterobacteria producing a broad-spectrum beta-lactamase; MEZLO, PIPER, CTX and CAZ in M. morganii producing a derepressed cephalosporinase. PMID- 1909018 TI - [Time-killing curves of Pseudomonas aeruginosa strains exposed to polymyxin B]. AB - The time-killing curves of three strains of Pseudomonas aeruginosa (PA01, ATCC10145 and ATCC27853) exposed to five concentrations of polymyxin B comprised: a latency phases, one or two decreasing phases and for the low polymyxin B concentrations a growth phasis. The five antibiotic concentrations were chosen to have a weak bactericidal effect such that decreasing exponential or biexponential models can be fitted to the data. In our experimental conditions, increasing Ca++ and Mg++ concentrations in the medium (Mueller-Hinton) reduced the bactericidal effect and increased the growth phases. Increasing inoculum (10(5) to 10(7) CFU/ml) decreased the bactericidal effect observed with polymyxin B. PMID- 1909017 TI - [In vitro antibacterial activity of a new oral cephalosporin, ceftibuten. Results of a multicenter study]. AB - Minimal inhibitory concentration (MIC) of ceftibuten (CBT) were evaluated by agar dilution for 1,416 bacterial strains isolated in 5 hospitals. For Enterobacteriaceae, MIC 50 and 90% were respectively (micrograms/ml): (I) Naturally non beta-lactamase producing species: E. coli 0.12-0.5, Shigella 0.06 0.12 and Salmonella 0.03-0.12, P. mirabilis 0.16-0.03. (II) Chromosomal penicillinase producing species: K. pneumoniae 0.03-0.5 and K. oxytoca 0.03-0.06. (III) Chromosomal cephalosporin producing species: E. cloacae and C. freundii 1- greater than 128: S. marcescens 0.25-2; indole + Proteus 0.06-0.12. Activity of CBT was not modified on plasmid mediated penicillinase producing strains; however, CBT was inactive on cephalosporinase hyperproducing strains, and its activity was variably reduced on broad spectrum beta-lactamases producing strains. CBT was inactive on P. aeruginosa (MIC greater than or equal to 32) and on A. baumannii (8- greater than 128). Haemophilus and Gonococci, regardless on beta-lactamase production status, were very susceptible to CBT (MIC 50 and 90%: 0.06-0.5 and 0.016-0.06); it is the same situation for Meningococci; B. catarrhalis was generally inhibited by 0.03 to 2 (strains susceptible to penicillin G) and 0.12 to 16 (strains resistant to penicillin G). CBT was inactive on Staphylococci. Enterococci and Streptococci B were generally resistant; Streptococci A, C, G were inhibited by low concentrations: 0.06 to 1 (MIC 50 and 90%: 0.25-0.5), whereas MIC for other Streptococci 0.12 to 128 (MIC 50 and 90%: 8-128) and for Pneumococci were 0.25 to 16 (4-8). These antibacterial properties particularly against Enterobacteriaceae placed CBT in excellent position among oral cephalosporins. PMID- 1909020 TI - [Determination of antibacterial activity of antiseptic biotextiles in vitro after standard washings]. AB - A method in vitro is developed for evaluating antibacterial activity of antiseptic "biotextiles". The latter are particular in that they possess remanent antimicrobial properties, given their ability to carry antiseptic molecules. The method has to detect and measure a potential activity, but also point out it's stability. The biotextile and an appropriated control were repeatedly washed, put in contact with reference bacterial strains and subsequently incubated. The survival bacteria are then plated and counted by method of successive dilution. Compared with the controls, all the washed biotextiles presented a significant activity. PMID- 1909021 TI - [Nosocomial infections in an urological department. Incidence and etiological factors]. AB - The authors report a prospective study with active request of data for nosocomial infections (NI) in an urological department during six months. From 453 patients, 43 developed an NI (incidence = 9.5%): urinary tract infections (53.5%), bloodstream infections (16.3%), lower respiratory tract infections (7%), surgical wound infections (2.3%) and sepsis syndrome (20.9%). For microorganisms, most often Pseudomonas aeruginosa (22.5%) and E. coli (20%) were encountered. Other microorganisms were the next-ones: Staphylococcus aureus (15%), Staphylococcus epidermidis (7.5%), Acinetobacter baumanii (7.5%), Streptococcus group D (7.5%), Klebsiella pneumoniae (7.5%), Candida albicans (2.5%) and others (10%). Urological interventions with a high risk of NI were cystectomy with intestinal urinary diversion (68.7%), pyeloplasty for ureteropelvic junction obstruction (40%) and percutaneous nephrolitothomy (30%). Even if the last two interventions classically do not have a high risk of NI, we think that their antibioprophylaxis is recommended. PMID- 1909019 TI - [First isolation in France of a penicillinase-non producing Neisseria gonorrhoeae with high level tetracycline resistance]. AB - We report the first isolation in France of a penicillinase-non producing Neisseria gonorrhoeae with high level tetracycline resistance. The minimal inhibitory concentrations (MICs) of nine antibiotics were determined by agar dilution for the tetracycline resistant strain and 39 other penicillinase-non producing N. gonorrhoeae strains which were isolated during the same year (1989), in Toulouse. No difference was observed between the MICs except for the tetracycline (tetracycline-resistant strain MIC = 32 mg/l). The commonly used antibiotics other than tetracycline were active in vitro against all the strains. The plasmid content of the tetracycline-resistant strain was analysed by agarose gel electrophoresis and revealed the presence of two plasmids: the 2.6-megadalton in cryptic plasmid and the 25.2-megadalton Tet M conjugative plasmid. PMID- 1909022 TI - [Effect of mold mycotoxins on the morphofunctional state of the small intestine of rats]. AB - The entry of metabolites of the Aspergillus flavus mold into the gastrointestinal tract (GIT) with the food for one week causes inhibition of the activity of ATPase, cytochrome oxidase, and alkaline phosphatase; paranecrotic and morphologic changes in the tissue of the smooth muscles of the small intestine are encountered, which, evidently, underlies the disorders of intestinal digestion. The morphofunctional status of the small intestine is restored 5 days after the supply of mold metabolites into the GIT ceases. PMID- 1909023 TI - Circulating catecholamine concentrations in cocaine-exposed neonates: a pilot study. AB - Twenty newborns, 12 with prenatal exposure to cocaine and an unexposed control group of 8, were studied to determine concentrations of circulating catecholamines and their relationship to newborn behavior. Birth weight of the cocaine-exposed neonates was significantly lower than that of the control group. Gestational age, length, and head circumference of the cocaine-exposed neonates were also lower, although the differences did not reach statistical significance. Between 24 and 48 hours of age, circulating concentrations of norepinephrine, dopamine, and the catecholamine precursor dihydroxyphenylalanine were measured and behavior was assessed using the Neonatal Behavioral Assessment Scale. Mean dihydroxyphenylalanine concentrations were increased in the cocaine-exposed newborns (10.3 ng/mL vs 5.9 ng/mL, P = .055), while there was no difference between the groups in mean norepinephrine or dopamine concentrations. There was a significant negative correlation between norepinephrine concentration and orientation cluster score for the cocaine-exposed newborns (r2 = .6979, P = .005). norepinephrine concentration did not correlate with the score for any other behavioral cluster, nor did dopamine or dihydroxyphenylalanine concentration correlate with the score for any cluster. These preliminary data from a pilot study suggest that catecholamine activity is increased in cocaine exposed newborns and may play a role in neurobehavioral disturbances associated with prenatal exposure to this drug. PMID- 1909025 TI - Comparison of Gluma bond strength to primary vs. permanent teeth. AB - The purpose of this study was to measure the shear bond strength of Gluma/Lumifor (Gluma and Lumifor--Columbus Dental, St. Louis, MO) to the occlusal dentin of primary first and second molars, permanent first and second molars and premolars. The data were examined for differences using a one-way analysis of variance and Duncan's Multiple Range test. The shear bond strength, (kc/cm2, x +/- SEM) to primary molars was 85.6 +/- 13.7, to permanent molars was 110.1 +/- 9.3, and to premolars was 124.0 +/- 9.3. Gluma/Lumifor provides moderately good bonding to dentin. The bond strengths of Gluma/Lumifor to primary molars was statistically significantly lower than to permanent teeth. PMID- 1909024 TI - Pulp response to collagen and glutaraldehyde in pulpotomized primary teeth of baboons. AB - This investigation assessed histologically the pulp tissue reaction to glutaraldehyde (GA) and to a commercial collagen preparation in pulpotomized primary teeth of baboons. One hundred and eighty-eight primary teeth were pulpotomized; in half of them inflammation was induced prior to the treatment. The teeth were divided into five groups: in three of them GA was used as a pulp dressing and applied for 1 min (group 1), 5 min (group 2), or mixed into the paste (group 3); collagen was used in group 4 and in group 5 (control) IRM was placed directly over the pulp stumps. Follow-up times were two, eight, and 24 weeks. Total necrosis was observed only in the collagen group. Partial necrosis and severe inflammation also were seen mainly in this group, and when the GA was incorporated into the paste. Slight to moderate inflammation was evident in all groups two and eight weeks postoperatively; however, 78% of the teeth of group 2 (GA 5 min) were inflammation-free after 24 weeks. Partial dentin bridges were seen in 92% of the teeth of the control group, in 82% of group 2, and 50% each of groups 1 and 3 eight weeks postoperatively. Dentin bridges were present in only 4% of the collagen group. After 24 weeks, all the teeth in group 2 and 83% of group 1 had dentin bridges. We conclude that Zyderm (Colagen Corp. Palo Alto, CA) led to unacceptable results, 5 min application of GA presented the best healing response, and GA 1 min and IRM also were satisfactory. PMID- 1909026 TI - Overlapping loss of heterozygosity by mitotic recombination on mouse chromosome 7F1-ter in skin carcinogenesis. AB - A significant role for mouse chromosome 7 abnormalities during chemically induced skin carcinogenesis has been advanced based on previous cytogenetic and molecular studies. To determine the frequency of allelic losses at different loci of chromosome 7 in skin tumors induced in the outbred SENCAR mouse stock by a two stage initiation-promotion protocol, we compared the constitutional and tumor genotypes of premalignant papillomas and squamous cell carcinomas for loss of heterozygosity at different informative loci. In a previous study, these tumors had been analyzed for their allelic composition at the Harvey ras-1 (Ha-ras-1) locus and it was found that 39% of squamous cell carcinomas had lost the normal Ha-ras-1 allele exhibiting 3 or 2 copies of the mutated counterpart or gene amplification. In the present study, by combining Southern blot and polymerase chain reaction fragment length polymorphism analyses, we detected complete loss of heterozygosity at the beta-globin (Hbb) locus, distal to Ha-ras-1, in 15 of 20 (75%) skin carcinomas. In addition, 5 of 5 informative cases attained homozygosity at the int-2 locus, 27 centimorgans distal to Hbb. Polymerase chain reaction analysis of DNA extracted from papillomas devoid of stromal contamination by fluorescence-activated sorting of single cell dispersions immunolabeled with anti-keratin 13 antibody revealed loss of heterozygosity at the Hbb locus, demonstrating that this event occurs during premalignant stages of tumor development. Interestingly, loss of heterozygosity was only detected in late-stage lesions exhibiting a high degree of dysplasia and areas of microinvasion. Analysis of allelic ratios by densitometric scanning of tumors that had become homozygous at Hbb but retained heterozygosis at Ha-ras-1 indicated mitotic recombination as the mechanism underlying loss of heterozygosity on mouse chromosome 7 during chemically induced skin carcinogenesis. These findings are consistent with the presence of a putative tumor suppressor gene linked to the Hbb locus in the 7F1-ter region of mouse chromosome 7, the functional inactivation of which may constitute a critical event in skin tumor progression, possibly during the malignant conversion stage. PMID- 1909027 TI - Cloning of a cellular factor, interleukin binding factor, that binds to NFAT-like motifs in the human immunodeficiency virus long terminal repeat. AB - Human immunodeficiency virus (HIV) gene expression is regulated by both general transcription factors and factors induced by activation of T lymphocytes such as NF-kappa B and the nuclear factor of activated T cells (NFAT). Within the HIV long terminal repeat (LTR), two purine-rich domains between nucleotides -283 and 195 have homology to a regulatory region found in the interleukin 2 promoter, which binds NFAT and other cellular factors. In the HIV LTR, this region has been demonstrated to have both positive and negative regulatory effects on HIV gene expression. In an attempt to clone genes encoding cellular factors that bind to these NFAT-like elements in the HIV LTR, we used lambda gt11 expression cloning with oligonucleotides corresponding to these binding motifs. A ubiquitously expressed cDNA encoding a 60-kDa protein, which we termed interleukin binding factor (ILF), binds specifically to these purine-rich motifs in the HIV LTR. This factor also binds to similar purine-rich motifs in the interleukin 2 promoter, through with lower affinity than to HIV LTR sequences. Sequence analysis reveals that the DNA binding domain of ILF has strong homology to the recently described fork head DNA binding domain found in the Drosophila homeotic protein fork head and a family of hepatocyte nuclear factors, HNF-3. Other domains found in ILF include a nucleotide binding site, an N-glycosylation motif, a signal for ubiquitin-mediated degradation, and a potential nuclear localization signal. These results describe a DNA binding protein that may be involved in both positive and negative regulation of important viral and cellular promoter elements. PMID- 1909028 TI - Agrobacterium rhizogenes pRi8196 T-DNA: mapping and DNA sequence of functions involved in mannopine synthesis and hairy root differentiation. AB - This paper presents the map and DNA sequence analysis of pRi8196 transferred DNA (T-DNA) genes encoding root-inducing and mannopine synthesis functions. A canonical 24-base-pair border repeat as well as two "pseudoborders" are present at the functional right T-DNA border. To the left of this border are homologs of the mas1' and mas2' genes of TR pRiA4. Next to these are five open reading frames (ORFs) homologous to ORFs 10-14 of TL of pRiA4. ORFs 10-12 (rolA, rolB, and rolC) are less related to their pRiA4 homologs than are the other large ORFs analyzed here. In contrast to T-DNA genes of pRiA4, pRi8196 T-DNA ORFs 11 and 12 (rolB and rolC) are sufficient to induce hairy roots on carrot disks. PMID- 1909029 TI - Translation and the stability of mRNAs encoding the transferrin receptor and c fos. AB - Turnover of the full-length human transferrin receptor (TfR) mRNA is regulated by iron, and this regulation is mediated by the transcript's 3' untranslated region. Alterations in the sequence of the TfR mRNA regulatory region have been identified that render the mRNA unregulated by iron and intrinsically unstable. When cells expressing this unstable mRNA are treated with inhibitors of protein synthesis (cycloheximide or puromycin), the steady-state level of the encoded human TfR mRNA is increased due to a stabilization of the transcript. A similar set of observations has been made using a chimeric mRNA in which the rapid turnover determinant of the TfR mRNA is replaced by the (A+U)-rich region from the 3' untranslated region of c-fos mRNA. To distinguish between a labile protein participant in the degradation of these mRNAs and a requirement for their translation per se, we introduced a ferritin iron-responsive element into the 5' untranslated region of each of these mRNAs. The presence of the 5' iron responsive element allowed us to use iron availability to alter the translation of the mRNAs in question without global effects on cellular protein synthesis. Although specific translation of these mRNAs could be inhibited by iron chelation to a degree comparable to that seen with cycloheximide (approximately 95% inhibition), no effects on mRNA turnover were observed. These data support a model in which a trans-acting labile protein is necessary for the turnover of these mRNAs rather than there being a requirement for the translation of the mRNAs themselves. PMID- 1909031 TI - Envelope proteins from clinical isolates of human immunodeficiency virus type 1 that are refractory to neutralization by soluble CD4 possess high affinity for the CD4 receptor. AB - Recent evidence indicates that primary clinical isolates of human immunodeficiency virus type 1 (HIV-1) require significantly more soluble CD4 (sCD4) to block infection than the prototypic laboratory strain HTLV-IIIB. The currently accepted explanation for these observations is that the envelope glycoproteins from primary clinical isolates possess lower affinities for CD4 than laboratory strains. This observation has far reaching implications for the clinical effectiveness of sCD4. To test whether the resistance of clinical isolates to sCD4 neutralization correlates with low-affinity binding to gp120, we have compared gp120 glycoproteins derived from the clinical isolates HIV-1 JR-CSF and JR-FL with those derived from the prototypic strain HIV-1 BH10 in quantitative sCD4 binding studies. Surprisingly, our results demonstrate that gp120 derived from HIV-1 JR-CSF and JR-FL possess sCD4 binding affinities of equal or greater magnitude than gp120 derived from HIV-1 BH10. Thus primary clinical HIV-1 isolates can and do possess gp120 with high affinity for CD4, and sensitivity to neutralization by sCD4 is dependent upon factors other than the intrinsic affinity of gp120 for CD4. PMID- 1909030 TI - Molecular characterization of five human anti-human immunodeficiency virus type 1 antibody heavy chains reveals extensive somatic mutation typical of an antigen driven immune response. AB - We report the heavy chain variable region sequences from the cDNAs of five previously described monoclonal cell lines producing human antibodies specific for the human immunodeficiency virus type 1 and detail the molecular characteristics, germ-line origins, and extent of somatic mutation among these antibodies. Three of the five heavy chain variable regions derive from the VHIV gene family, but each has arisen from a different heavy chain variable region (VH) gene segment within the VHIV family. In addition, one is derived from a VHI gene segment, and one is derived from a VHV gene segment. Since four of the five antibodies arise from known germ-line VH elements, a precise determination of the extent of somatic variation is possible. The amount of variation from the closest germ-line sequence ranges from 4.5% to 14.8% among these antibodies, most of which is concentrated in the complementarity-determining regions. In general, the diversity (D) segments are long, characteristic of D-D fusions and/or extensive terminal deoxynucleotidyltransferase activity; however, definitive homologies cannot be found with the known germ-line D segments. Joining (JH) gene segment utilization appears random. The use of five different germ-line VH gene segments and extensive somatic mutation provides evidence that a polyclonal, antigen driven immune response occurs during the natural infection with human immunodeficiency virus. PMID- 1909032 TI - Mechanism of phenolic activation of Agrobacterium virulence genes: development of a specific inhibitor of bacterial sensor/response systems. AB - The aglycone of the dihydrodiconiferyl alcohol glycosides, a series of phenolic growth factors able to substitute for some of the hormone requirements of tobacco cell division, are also potent inducers of virulence gene expression in Agrobacterium tumefaciens. However, these factors do not conform to the previously established structural requirements necessary for vir expression. Systematic evaluation of the structural requirements of these inducers has led to a model detailing the role of the phenolics in induction. With this model, a specific inhibitor of vir induction has been developed. This inhibitor does not affect the induction of other genes on the Ti plasmid but irreversibly blocks vir expression. The inhibitor has been used to show that the inducing phenolics must be constantly present to maintain expression of the vir regulon. PMID- 1909033 TI - The enzymes in cyclooxygenase and lipoxygenase pathways of arachidonic acid metabolism in human corpora lutea: dependence on luteal phase, cellular and subcellular distribution. AB - Eicosanoids synthesized within corpus luteum are presumed to regulate luteal function in women. However, the potential cellular source(s) of the eicosanoids, whether small and large luteal cells differ in eicosanoid synthesis and whether eicosanoids other than prostaglandin (PG)E2, PGF2 alpha and 6-keto-PGI1 alpha can be synthesized, have not been investigated. The present immunocytochemical studies were undertaken to answer these questions using mono and polyclonal antibodies to several enzymes in arachidonic acid metabolism by cyclooxygenase and lipoxygenase pathways. Human corpora lutea from early (n = 5), mid (n = 6) and late (n = 3) luteal phases were specifically immunostained for all the enzymes. All the enzymes were present in small and large luteal cells as well as in non luteal cells. However, small luteal cells contained more immunoreactive 5 lipoxygenase, PGD2 and PGF2 alpha synthases; large luteal cells contained more TXA2 synthase and 12-lipoxygenase; small and large luteal cells contained similar amounts of cyclooxygenase and PGI2 synthase. In all the cells, immunoreactive PGD2, PGI2 and TXA2 synthases increased from early to mid luteal phase and then declined in late luteal phase. Cyclooxygenase, 5- and 12-lipoxygenases and PGF2 alpha synthase, on the other hand, increased from early to mid and mid to late luteal phases. Immunoreactive cyclooxygenase and 5- and 12-lipoxygenases were present primarily in rough endoplasmic reticulum (ER) and/or smooth ER and cytoplasm. Quite unexpectedly, all three enzymes were also found in nuclear membranes, condensed chromatin and especially at the perimeter of condensed chromatin. Dispersed chromatin contained very little or no immunoreactive enzyme. These results indicate that regulation of human luteal function by eicosanoids synthesized within the corpus luteum is complex involving perhaps a) small and large luteal as well as non luteal cells, b) eicosanoids which have not been previously considered to play a role in luteal function and c) coordinate regulation of more than one enzyme in the pathways of arachidonic acid metabolism. PMID- 1909034 TI - Synthesis of certain 2-aminoadamantane derivatives as potential antimicrobial agents. AB - 1-(2-Adamantyl-3-(5-arylhydrazono-6-methyl-4-oxopyrimidin -2-yl)guanidines, 2-(2 adamantylamino)-4-amino-s-triazine and its 6-chloromethyl derivative were prepared by cyclization of 1-(2-adamantyl)biguanide.HCl with ethyl 2 arylhydrazono-3-oxobutyrates, ethyl formate and ethyl chloroacetate, respectively. 1-(2-damantyl)-3-(4,5-dioxo-2-imidazolidinylidene)guanidine was used as intermediate for the synthesis of amides, hydrazide and azomethine derivatives of alkyl 2-(2-adamantylamino)-4-amino-s-triazine-6-carboxylates. The antimicrobial testing of the prepared compounds proved that an azomethine derivative was the most active. It showed a marked bacteriostatic effect against Staphylococcus aureus and Bacillus subtilis. PMID- 1909035 TI - Lithium and hair loss in childhood. PMID- 1909036 TI - [Energy yielding metabolism of cyanophytes]. PMID- 1909037 TI - [Molecular organization of cyanobacterial photosystems]. PMID- 1909038 TI - [Nitrogen fixation in cyanophyta]. PMID- 1909039 TI - [The cyanobacterial membrane architecture in relation to the low-temperature tolerance]. PMID- 1909040 TI - [Transport systems in cyanobacteria]. PMID- 1909042 TI - [Genome structure, molecular genetics and genetic engineering of cyanobacteria]. PMID- 1909041 TI - [Osmoregulation in cyanobacteria]. PMID- 1909043 TI - [A list of cyanobacterial genes]. PMID- 1909044 TI - Prospective hospital study of community acquired lower respiratory tract infection in the elderly. AB - A prospective study of community acquired lower respiratory tract infection in the elderly was carried out over a 15-month period. During this time 127 consecutive admissions to two acute geriatric medical wards were studied. An aetiology was established in 77 (61%) of cases. Streptococcus pneumoniae was identified in 37% of patients. Haemophilus influenzae in 18% and Branhamella catarrhalis in 10%. Infection with Mycoplasma pneumoniae was found in only one episode and no cases of Legionella pneumophilia were diagnosed. A significant number of patients had multiple bacterial pathogens isolated: 18% of all bacterial pathogens isolated were ampicillin resistant. Fourteen patients died (11%). Lower respiratory tract infection is a frequent cause of hospital admission for those aged over 65 and is often regarded as a preterminal event. Adequately treated however, mortality is no higher than in the general population. Knowledge of the likely pathogens allows early and appropriate antibiotic therapy for these patients whether at home or on admission to hospital. PMID- 1909045 TI - Experience of tuberculosis in immigrants from South East Asia--implications for the imminent lease back of Hong Kong. AB - We have undertaken a retrospective survey of patients of South East Asian ethnic origin (SEA), presenting with tuberculosis (between 1980 and 1989) while resident in the Liverpool district. Of 708 notifications in the 10-year period, 42 (6%) were SEA patients mainly from Hong Kong or mainland China. A total of 22 (52%) of the SEA patients presented with an extrapulmonary site of disease. Drug resistance was present in 11% of those for whom sensitivity results were available. Rates of disease in Hong Kong are similar to those seen in the Indian Subcontinent (ISC) population in the U.K. With the expected immigration of Hong Kong Chinese and possibly other SEA individuals to the U.K. as a result of the lease back of Hong Kong in 1997, all clinicians must be alerted to the possibility of tuberculosis whenever these individuals present with disease. The high incidence of extra pulmonary disease in SEA immigrants is striking and similar to that seen in the ISC population. PMID- 1909046 TI - Tuberculosis of the ribs--a report of three cases. PMID- 1909047 TI - Reciprocal cellular and humoral immune responses in bovine tuberculosis. AB - A sandwich ELISA for the detection of gamma interferon showed higher sensitivity and specificity than an indirect ELISA for mycobacterial antibodies in the diagnosis of bovine tuberculosis. Circumstantial evidence of an inverse relationship between cellular and humoral immune responses to Mycobacterium bovis was found in cattle with natural infection. PMID- 1909048 TI - The relationship between age and venous plasma concentrations of noradrenaline, catecholamine metabolites, DOPA and neuropeptide Y-like immunoreactivity in normal human subjects. AB - Forearm venous plasma concentrations of noradrenaline (NA), catecholamine metabolites (dihydroxyphenylglycol (DHPG), dihydroxyphenylacetic acid (DOPAC], dihydroxyphenylalanine (DOPA) and neuropeptide Y-like immunoreactivity (NPY-LI) were studied in 22 men aged 20 to 81 years in the supine position and after 30 min of standing posture. Venous plasma NA, DHPG and NPY-LI increased significantly in the standing position, whereas venous plasma DOPAC and venous plasma DOPA remained unchanged. Increments in venous plasma NA and DHPG upon standing up, as well as venous plasma NA in the standing-up position, increased significantly with age. The ratio between increments in venous plasma DHPG and venous plasma NA did not change with age. Venous plasma NPY-LI and venous plasma DOPA did not change with age, whereas venous plasma DOPAC decreased significantly. Changes in venous plasma NPY-LI were negatively correlated with changes in pulse pressure. These results confirm previous studies that sympathetic activity increases with age. The unchanged ratio between increments in venous plasma DHPG and venous plasma NA suggests that intra-neuronal deamination of recaptured NA is unchanged in the elderly. The lower basal venous plasma DOPAC concentration may suggest a reduced basal intraneuronal synthesis of NA in old age. PMID- 1909049 TI - Dietary n-6 fatty acids inhibit the incorporation of dietary n-3 fatty acids in thrombocyte and serum phospholipids in humans: a controlled dietetic study. AB - The effect of a high dietary intake of n-6 fatty acids (36 g daily) vs a low intake (4-6 g daily) on the incorporation of fatty acids from a dietary supplementation of n-3 fatty acids (6 g daily) was studied for 8 weeks in 15 healthy, normolipaemic volunteers. The importance of a high (43.6) vs a low (20.6) energy percentage from fat was also investigated in the participants on a low n-6 intake. Fatty acid analyses of serum and thrombocyte phospholipids showed a marked increase in docosahexaenoic acid (22:6 (n-3), DHA) and especially eicosapentaenoic acid (20:5 (n-3), EPA) in both the high and low n-6 groups after 14 days, but the changes were significantly greater in the low n-6 diet groups. Changes of the ratio between EPA and arachidonic acid (20:4 (n-6), AA) in phospholipids followed an identical pattern in serum and thrombocytes. This indicates that thrombocytes are influenced by the fatty acid composition in serum. The results showed that incorporation of n-3 fatty acids in phospholipids was reduced by a high intake of dietary n-6 fatty acids in the cells and lipid fractions studied. The observed effect of dietary n-6 fatty acids was independent of the energy percentage provided by dietary fat. In order to obtain an optimal effect of n-3 supplementation, the intake of linoleic acid has to be considered and kept at a low level. The serum content of cholesterol was unaffected, but the concentration of triacylglycerol was reduced during the supplementation period. PMID- 1909050 TI - In vivo attachment of group A streptococci to tonsillar epithelium during acute tonsillitis. AB - The attachment of group A beta-hemolytic streptococci (GABHS) to the tonsillar epithelium during current acute tonsillitis (AT) was studied by means of fluorescence microscopy and electron microscopy in 5 patients. Conventional cultures from the tonsils showed massive growth of GABHS and tonsillar epithelial cells were heavily infested with GABHS, which proved positive for FITC-labelled antibodies against beta-hemolytic streptococci. The bacteria were firmly attached to the epithelial cell membranes by cell projections, which grasped the microorganisms from various directions. A 24 h course of oral treatment with phenoxymethylpenicillin radically affected bacterial adherence to the epithelial cells. PMID- 1909051 TI - Antimicrobial susceptibility of Bacillus anthracis. AB - 22 Bacillus anthracis isolates were tested for susceptibility to 27 antimicrobial agents by agar dilution. All isolates were sensitive to penicillins and did not produce beta-lactamase. Although all isolates were sensitive to cefazolin, cephalothin, cephradine and cefoperazone 19 isolates were resistant to cefuroxime, 18 to cefotaxime, 18 to ceftizoxime, 9 to ceftriaxone and 21 to ceftazidime. All isolates were also found to be sensitive to other antimicrobials tested. The new antimicrobial agents, ofloxacin and ciprofloxacin showed very good activity with MICs of 0.03-0.06 mg/l. PMID- 1909052 TI - Erythromycin and phenoxymethylpenicillin (penicillin V) in the treatment of respiratory tract infections as related to microbiological findings and serum C reactive protein. AB - Respiratory tract pathogens (beta-haemolytic streptococci groups A, C and G, Haemophilus influenzae, Branhamella catarrhalis or pneumococci), were isolated from nasopharyngeal and/or throat swabs in 73/138 (53%) patients greater than 10 years of age with a clinical diagnosis of acute sinusitis, acute tonsillitis, purulent nasopharyngitis or acute bronchitis. Serological evidence of a viral infection (influenza A and B, parainfluenza 1, 2 and 3, respiratory syncytial virus, adenovirus) or Mycoplasma pneumoniae infection was found in 10% of the patients. The serum content of C-reactive protein (S-CRP) was increased (greater than 12 mg/l) in 26/33 (79%) patients with streptococci and in 22/59 (37%) patients without respiratory tract bacteria. In patients with a serological evidence of a virus tonsillitis, the S-CRP was also high (32-64 mg/l). At follow up 10-12 days after the first visit, the clinical effect of erythromycin and penicillin V was judged to be similar (90% clinical effect). Relapse or re infection with group A streptococci were seen in 7 patients (4 on erythromycin, 3 on penicillin). In another 6 patients (3 on erythromycin, 3 on penicillin), antibiotic treatment was switched owing to persisting symptoms, probably due to H. Influenzae infection in 3 cases. The patients' own estimates of their symptoms suggested treatment with erythromycin to have a more rapid effect than treatment with penicillin. PMID- 1909053 TI - Alterations in oral microflora and pathogenesis of acute oral infections during remission-induction therapy in patients with acute myeloid leukaemia. AB - To investigate changes in the aerobic and facultatively anaerobic oral microflora during remission-induction chemotherapy in patients with acute myeloid leukaemia, 10 consecutive patients were studied during a period of 28 days. During antineoplastic treatment, the concentration of microorganisms in saliva doubled from day 0 to day 2, presumably as a result of a concurrent 64% decrease in the salivary flow rate. No changes in the relative proportion of individual microorganisms or acquisition of new microorganisms occurred during antineoplastic treatment. During antibacterial treatment, which was subsequently initiated in all patients, a 100-fold decline occurred in the median salivary concentration of microorganisms within the first 7 days. During this period, members of the normal flora became undetectable in 5 patients, and Enterobacteriaceae, Enterococcus faecalis or Candida spp. became parts of the quantitatively predominant oral microflora in 7 patients. Apart from Candida spp., these potentially pathogenic microorganisms were acquired only after the initiation of the antibacterial treatment. After termination of the antibacterial treatment, the median concentration of microorganisms increased again to the original level and normal flora became reestablished within a period of 8 days. Clinically, 10/20 acute oral infections emerged before day 8, i.e. within the period with increased concentrations of microorganisms in saliva. Specifically, the clinical diagnosis of acute oral candidiasis was associated with a rise in the concentration of Candida spp. above a critical value of 1,000 CFU/ml. Herpes simplex virus (HSV) type 1 was detected in 4/9 HSV-seropositive patients on days 14 and 21, and HSV-1 was in all 4 cases isolated simultaneously with the emergence of an intraoral ulcer. The results suggest that chemotherapy-induced xerostomia plays a significant role in the pathogenesis of acute oral infections and transmission of potentially pathogenic microorganisms is of importance mainly after initiated antibiotic treatment in these patients. PMID- 1909055 TI - [Synthetic analog of prostaglandin E2 (enprostil) in the treatment of peptic ulcer]. PMID- 1909054 TI - Partitioning and levels of neutral organochlorine compounds in human serum, blood cells, and adipose and liver tissue. AB - Concentrations of neutral organochlorine compounds (OCs) in blood compartments and adipose tissue were determined in three groups of subjects. In 12 healthy volunteers a positive correlation was found between DDT residue levels in paired serum/adipose tissue samples when the concentrations were calculated on a fat weight basis (r = 0.74, p less than 0.05); positive correlations were also found for PCB and HCB when the calculations were based on a wet-weight basis (r = 0.68, p less than 0.01; r = 0.69, p less than 0.01). For lindane the correlation coefficient for paired serum/adipose tissue samples was -0.94 (p less than 0.01). The association between adipose tissue and blood cells was weaker than that obtained for serum. These readily obtainable samples are adequate for estimating, or monitoring, the total burden of neutral organochlorines in adipose tissue, especially in cases of low chronic exposure, such as those found in epidemiological studies. In paired liver-adipose tissue samples from 23 autopsy cases, no correlation was found either on a wet- or fat-weight basis. In 131 adults resident in southern and eastern Finland the concentration medians for serum were 1.8, 2.0 and 0.3 ng g-1 wet wt for DDT compounds. PCB and HCB, respectively. This study indicates that monitoring of fat/serum ratios may provide, with tissue concentrations, more information about human exposure to OCs. PMID- 1909056 TI - [Microflora of clinical specimens from patients of the anesthesiological and resuscitation units]. PMID- 1909057 TI - Induction of natural killer (NK) activity in mice by injection of chromomycin A3. AB - Intravenously or intraperitoneally administered Chromomycin A3 (CHRM), an anticancer drug, augmented natural killer (NK) activity of both spleen cells and peritoneal exudate cells in BALB/c mice. When CHRM was administered intravenously, NK activity increased to about five fold that in nontreated mice on the 3rd to the 5th day, then rapidly decreased by the 7th day. On the other hand, when CHRM was administered by the intraperitoneal route, a peak of increased NK activity was observed on 5th to 7th day followed by a more gentle decrease. Augmentation of NK activity by CHRM was enhanced by additional administration of Interferon- gamma (IFN-gamma). Experimental evidence that NK activity could be augmented by CHRM in various strains of mice, independent of H 2 haplotype, suggested that involvement of genetic control within class I region of major histocompatibility complex could be excluded. When BALB/c mice inoculated subcutaneously with Meth A cells were treated with i.p. injection of CHRM, or CHRM in combination with IFN-gamma, the growth of the tumor cells was inhibited, indicating in vivo significance for the increased NK activity. Since this inhibitory effect was decreased by the injection of anti Asialo GM1 antibody (alpha-ASGM1), the effector cells presumably exerting killing activity against Meth A cells were concluded to be Asialo GM1 antigen positive. PMID- 1909058 TI - Nucleotide sequence of the putative human tyrosinase pseudogene. AB - We have cloned and sequenced the putative human tyrosinase pseudogene, which shares more than 98% nucleotide homology with exon 4 and exon 5 of the human tyrosinase gene including their flanking introns. Because of such a high homology, both the tyrosinase gene and its pseudogene could be amplified from genomic DNA by polymerase chain reaction. The nucleotide sequences presented thus enable us to discriminate the tyrosinase gene from its related sequences and are invaluable for a gene diagnosis of oculocutaneous albinism. PMID- 1909059 TI - Effects of thiourea on pulmonary vascular permeability and on lung and plasma histamine levels in rats. AB - The intraperitoneal administration of thiourea (TU) to mature male rats results in a significant increase in lung vascular permeability to Evans Blue dye (EBD). On the other hand, young, sexually immature rats are resistant to this effect. The increase in lung vascular permeability in response to TU in mature rats is associated with corresponding increases in lung and plasma histamine levels. The correlation of increases in lung and plasma histamine in response to TU is similar to that reported for ammonium salts which produce similar pulmonary edema. PMID- 1909060 TI - Clathrin- and non-clathrin-coated vesicle adaptors. PMID- 1909061 TI - Tuberculosis in Saudi Arabia: initial and secondary drug resistance among indigenous and non-indigenous populations. AB - Resistance to six anti-mycobacterial agents rifampicin, isoniazid, streptomycin, ethambutol, p-amino salicylic acid and cycloserine was studied. Variations in the resistance pattern among Saudi, non-Saudi and a stable National Guard King Khalid Hospital (NGKKH) population were investigated. A high percentage of relapse cases, 21%, was recorded. Among the NGKKH population this figure was much lower, 9.9%. Resistance to rifampicin alone was high at 7.2% followed by streptomycin 3.3%, isoniazid 1.8%, p-amino salicylic 1.2% and cycloserine 0.8%. Resistance to rifampicin alone was higher among 'new' cases whilst combined resistance to two or more drugs was seen more often in 'old' patients. Resistance was seen more frequently among non-Saudis, both 'old' and 'new'. An unusual finding was the prevalence of rifampicin resistance among non-pulmonary isolates. PMID- 1909062 TI - Activities of pefloxacin and ofloxacin against mycobacteria: in vitro and mouse experiments. AB - The minimal inhibitory concentrations for 90% of strains (MIC90) of ofloxacin against Mycobacterium tuberculosis and Mycobacterium xenopi was 2 mg/l. This was three dilutions lower than that of pefloxacin and was well within the range of drug concentrations achievable in man. The antituberculosis activities of both quinolones were independent of resistance of the strains to other antimycobacterial agents. Mycobacterium avium-intracellulare was resistant to both compounds with MIC90s greater than 16 mg/l. The maximum serum levels (Cmax) of both compounds increased proportionally with increasing dose size. The terminal elimination half-life (T1/2) of pefloxacin was longer than that of ofloxacin, but the T1/2 of both compounds in mice were much shorter than in man. The area under the concentration curve (AUC) of pefloxacin was double than that of ofloxacin. In the mouse, pefloxacin at doses up to 150 mg/kg daily was inactive against M. tuberculosis infection: in terms of survival rate the minimal effective dose of ofloxacin against M. tuberculosis infection was 150 mg/kg daily when given by gavage or by incorporation into the mouse diet at a concentration of 0.1%, but in terms of cfu counts, ofloxacin 150 mg/kg daily only displayed a moderate degree of activity similar to ethambutol 100 mg/kg daily. The therapeutic effects of ofloxacin against M. tuberculosis infection were dose related: 300 mg/kg daily by gavage or 0.4% in mouse diet displayed much better therapeutic effects than lower dosages. Since the AUC in mice treated with ofloxacin 150 mg/kg daily is close to that in man treated with a clinically tolerated dose--600 mg daily--such a dosage may be only moderately effective against human tuberculosis. PMID- 1909063 TI - [Metabolism and modification of high mobility proteins (HMG) in the liver of rats of various age]. AB - It is shown that heterogeneity of the high-mobility -group proteins (HMG proteins) in the rat liver does not depend on the animal age, while relative content of certain classes of these proteins and the HMG-proteins H1 histones ratio obeys age specificity. Metabolism of HMG 1 and 2 proteins in animals who have not achieved sexual maturity is low; the intensity of inclusion of labelled predecessors to proteins HMG 14', 17 and 17' decreases in the postnatal ontogenesis. The highest of HMG-proteins is observed in the liver of young (3 months) animals. In old (24 months) rats this process is inhibited. At all the stages of postnatal ontogenesis in the ribosylation intensity of HMG-proteins 14', is higher than that of the other classes of these proteins. The intensity of ribosylation of most fractions of HMG-proteins increases after 12 months. PMID- 1909064 TI - Common antigens of Fasciola gigantica, Dicrocoelium hospes and Schistosoma bovis and their relevance to serology. AB - The possession of common antigens by three trematode parasites which commonly occur together in ruminants in the tropics, Fasciola gigantica, Dicrocoelium hospes and Schistosoma bovis was studied in relation to the reliability of serodiagnosis of infection with these helminths. The crude antigenic extracts of the three trematodes were subjected to Sephacryl S-300 column chromatography and F. gigantica was fractionated into six peaks, S. bovis into nine peaks and D. hospes into seven peaks. Common antigens were found in these three trematodes in both the crude whole worm antigenic extracts and in the semi-purified fractions obtained by Sephacryl S-300 column chromatography. The implications of this finding and the limitation it imposes on the usefulness of serodiagnostic tests in routine use as regards their specificity are discussed in relation to previous studies. PMID- 1909065 TI - Some aspects of the gastrointestinal microflora of veal calves fed different rations: a pilot study. AB - The gastrointestinal microflora of veal calves reared on different diets was studied because the nature of this microflora affects the quality of veal as a result of contamination of carcass surfaces with intestinal contents during slaughter. Diet A consisted of a milk substitute, diet B of milk substitute + straw pellets and diet C of milk substitute + straw pellets + concentrates. In the rumen fluid of calves reared on diet A significantly higher counts of Gram negative bacteria but lower counts of thermotrophic enterobacteriaceae were found than in calves reared on diets B or C. As for the faecal flora, diets B and C seem to result in significantly lower counts of Gram-negative bacteria and thermotrophic enterobacteriaceae. In 46% of the faecal specimens and 62% of the specimens of rumen fluid from calves fed on milk substitute only, Pseudomonas aeruginosa was isolated in mean counts of 4.1 log cfu/g and 5.2 log cfu/g respectively. P. aeruginosa could not be isolated from any specimen from calves receiving straw pellets. These results indicate that the inclusion of straw pellets in the diet of veal calves may increase the bacteriological safety and keeping quality of veal. PMID- 1909066 TI - Acquisition of resistance to the bont tick Amblyomma hebraeum (Acarina: Ixodidae) by goats. AB - Goats acquired resistance to larvae of Amblyomma hebraeum following three repeated infestations. Resistance was associated with immediate Type I hypersensitivity reactions following intradermal skin tests using crude egg extracts. In a separate experiment, the inoculation of tick-naive goats with extracts of the larvae of A. hebraeum failed to induce observable effects on feeding larvae despite the development of anti-larval antibodies. PMID- 1909067 TI - Haemorrhagic septicaemia: correlation of vaccinal antibody responses in mice with protection against Pasteurella multocida strain M1404. AB - This study examined the protection induced by oil adjuvant vaccine and broth bacterin in mice. Protective immunity was induced by both oil adjuvant and bacterin vaccination procedures. Oil adjuvant vaccination induced a 10(5)-fold increase for lethal challenge over control mice, while secondary vaccination induced a further 10-fold increase in resistance to lethal challenge. Broth bacterin induced a slightly weaker protective response with 10(4)- and 10(5)-fold increases in resistance to lethal challenge following primary and secondary vaccination, respectively. There was a significant relationship between IgG antibody levels and resistance to challenge (P = 0.026). Protection lasted for at least 20 weeks after a primary oil adjuvant vaccination. There was also a strong and significant relationship between IgG antibody levels and the passive protection afforded by serum transfer in each experiment within this study and the overall correlation was highly significant (P = 0.00001). There appeared to be a relationship between protection and the antibody response to major protein bands with the apparent molecular mass Mr. 94,000; 80,000; 67,000; 35,000 and 32,000 as well as to the bands in the region of the lipopolysaccharide components of P. multocida (approximately Mr, 14-15,000). Whether protection resulted from recognition of specific antigens or was a result of both antibody levels and antibody specificity remains to be defined. PMID- 1909068 TI - SDS-soluble and peptidoglycan-bound proteins in the outer membrane-peptidoglycan complex of Brucella abortus. AB - Outer membrane-peptidoglycan complex from Brucella abortus was separated from cytoplasmic membrane and cytosol by either sucrose density gradient fractionation or differential (rate) centrifugation of surface labeled cells disrupted by sonication without the use of detergents. The outer membrane-peptidoglycan complex had a buoyant density of 1.22 gm/ml and contained 67 labeled SDS-soluble proteins when examined by SDS-PAGE. Included were four major bands exhibiting molecular masses of 88k, 40k, 35.7k and 26k daltons corresponding to previously described group 1, 2 and 3 outer membrane proteins. Lysozyme treatment of outer membrane-peptidoglycan complex increased its buoyant density to 1.25 gm/ml and released eight additional peptidoglycan-linked proteins. PMID- 1909070 TI - Neutrophil adherence, phagocytic-nitroblue tetrazolium reduction and chemiluminescence in canine whole blood. AB - Methods for measuring neutrophil adherence, phagocytic-nitroblue tetrazolium (NBT) reducing activity and chemiluminescence were applied to canine whole blood as means for routine assessment of neutrophil functions. The phagocytic-NBT reduction test appeared to be useful for monitoring the NBT reducing activity of phagocytic cells associated with phagocytic functions. Ethylene diamine tetraacetic acid suppressed both the adherence and the phagocytic-NBT reducing activity of neutrophils. Increased phagocytic-NBT reduction and an enhanced chemiluminescence response were observed in dogs with neutrophilia. These methods provide a rapid and practical screening procedure for measuring selected phagocytic functions in canine whole blood. PMID- 1909069 TI - Impaired thermal inactivation of ME7 scrapie agent in the presence of carbon. PMID- 1909071 TI - [The effect of a persistent viral infection on natural antitumor resistance]. AB - The influence of persistent infection with Tahyna virus on the natural antitumor resistance of the hosts was studied in mature mice. The infection was shown to suppress the host natural antitumor resistance. The development of infection was accompanied by a decrease of natural killer cell cytotoxicity against YAC-1 cell line within 7 days after virus inoculation. In this period, the transplantation dose of tumor cells decreased from 10(1.73) to 10(0.82). This indirectly indicates a potential ability of viruses with immunosuppressive activity to increase the frequency of development of malignant tumors. PMID- 1909072 TI - [The experimental and clinical antitumor action of the interferon inducer larifan]. AB - The paper presents the results of experimental and clinical studies on the antitumor effect of larifan. A statistically significant inhibition of growth of some continuous mouse tumors by larifan in a dose of 2.5 mg/kg given for 5-6 days and by a combination of larifan with an immunomodulator, inosiplex, tested on hepatoma XXIIa which has a rather low sensitivity to larifan. The antitumor effect of larifan may be due to interferon production and immunomodulating effect. Treatment with 0.05% larifan ointment of patients with cervical dysplasia of moderate degree resulted in a significant increase of previously diminished production of alpha-interferon after 10-14 vaginal tampons and clinical cure in 88% of cases. A course of 8-10-day larifan monotherapy given before radial therapy resulted in a considerable improvement in patients with cervical cancer of II-III stages, and subsequently, for 1 1/2-month combined radial therapy, no significant changes in production of alpha-IF were observed. At the same time, in patients with cervical cancer treated by radial therapy alone a significant decrease of alpha-IF production by blood mononuclears was observed by the end of therapy. PMID- 1909073 TI - The YGL023 gene encodes a putative regulatory protein. PMID- 1909074 TI - [Brucellar antibody erythrocytic diagnostic agent made from monoclonal antibodies]. AB - Two preparations based on monoclonal antibodies to bacteria of the genus Brucella have been obtained. From the monoclonal preparations and globulins isolated from them erythrocyte diagnostica have been obtained with the use of amidol. Experiments on the cross indication of brucellae and other bacteria by means of these diagnostica and a similar preparation obtained from polyclonal serum have shown very high specificity of erythrocyte immunoreagents prepared from monoclonal antibodies. PMID- 1909075 TI - [The characteristics of Corynebacterium diphtheriae adhesins]. AB - The study of the properties of C. diphtheriae adhesins revealed the absence of their thermostability, which suggested the protein nature of these adhesins. C. diphtheriae also showed pronounced mannose-resistant hemagglutinating activity, as this activity remained unchanged even in the presence of d-mannose. The comparison of the adhesive activity of C. diphtheriae with their phage and corycine sensitivity revealed essential differences between these macroorganisms in the degree of their adhesiveness. The phage lysability and corycine sensitivity of C. diphtheriae strains, determined by the properties of their surface structure, correlated with the degree of their activity. PMID- 1909076 TI - [A comparative analysis of different methods for the serological diagnosis of epidemic typhus]. PMID- 1909077 TI - [Mycobacterial antigens and their diagnostic value]. PMID- 1909078 TI - [The action of helium-neon laser radiation on the growth of Mycobacterium tuberculosis]. AB - The growth properties of M. tuberculosis subjected to the action of helium-neon laser radiation was studied. Laser radiation was shown to change the quantitative and qualitative composition of mycobacterial population. Disturbances in the viability of mycobacteria appear as a consequence of changes in the morphological structure of mycobacterial cells. The maximum effect of helium-neon laser radiation was achieved after the irradiation of M. tuberculosis culture on days 2 3 after inoculation. These results made it possible to suggest that the effect of helium-neon laser radiation was most pronounced in cells at the stage of mitosis (the logarithmic stage of growth) with the highest degree of metabolism. PMID- 1909080 TI - Excretion of phenoxymethylpenicillin in the vaginal fluid of hysterectomized women. AB - The excretion of phenoxymethylpenicillin in vaginal fluid was determined in 19 hysterectomized women, 8 totally and 11 subtotally operated. Phenoxymethylpenicillin was found in the vaginal fluid in high concentrations in both groups of women and it was concluded that the substance penetrates the vaginal wall. Concentrations were significantly higher in the most distal part of the vagina. The possible mechanisms for this phenomenon are discussed. PMID- 1909079 TI - Immunohistological study on brains of Alzheimer's disease using antibodies to fetal antigens, C-series gangliosides and microtubule-associated protein 5. AB - An immunohistological study of Alzheimer's brains was performed using antibodies to C-series gangliosides and microtubule-associated protein 5 (MAP5), and their staining patterns were compared with those of antibodies to tau and beta-amyloid precursor protein. Antibodies to C-series gangliosides and MAP5, both of which are known to preferentially expressed in the fetal brains, immunostained dystrophic neurites of senile plaques, neurofibrillary tangles and neuropil threads abundant in 3rd and 5th layers in the cerebral cortex, all of which are considered to be pathological hallmarks of Alzheimer's disease. The immunostaining patterns of these structures by antibodies to C-series gangliosides and MAP5 were similar to those by the antibody to tau. These three antibodies also immunostained some neurons in Alzheimer's brain, although their staining patterns were slightly different from one another; i.e., both diffuse and granular patterns were seen by the antibody to tau, but only granular pattern by the antibodies to C-series gangliosides and MAP5. These neurons immunostained by these three types of antibodies appeared to be the precursors of the classical neurofibrillary tangles, as positively stained neurons were not seen in the brains of non-demented cases. The presence of fetal antigens such as the C-series gangliosides and MAP5 in Alzheimer's brain may suggest that regeneration or sprouting of neurons is ongoing in association with the re-induction of gene expression characteristic for the brain in the early stage of development. PMID- 1909081 TI - Mechanical knot performance of a new generation polydioxanon suture (PDS-2). AB - To improve the handling characteristics of synthetic resorbable monofilament PDS (polydioxanon), a second-generation (PDS-2) suture has been developed. The mechanical knot performance of this suture was tested in square knots and sliding knots and compared with other monofilament suture materials. Knot performance was defined by the loop holding capacity (LHC) and expressed in Newton's (N). Maxon (polyglycolid-three-methylene carbonate) had significantly better knot performance than the other sutures. Knot performance of Prolene (polypropylene) was significantly poorer than that of the other sutures. Ordinary PDS (polydioxanon) and PDS-2 (polydioxanon) showed intermediate results. Knot performance of PDS-2 was similar to (square knots) or poorer than (sliding knots) that of ordinary PDS. It was concluded that knot performance of ordinary PDS is not improved by the introduction of PDS-2. It is emphasized that surgeons should be aware of the mechanical properties of newly developed suture materials. Underlying factors and clinical implications of the mechanical performance of PDS 2 are discussed. PMID- 1909082 TI - The effect of hyaluronic acid on cartilage in the immobilized rabbit knee. AB - Out of 30 adult rabbits, 20 had one knee immobilized with a plaster of Paris cast for 6 or 12 weeks, and 10 rabbits were used as untreated controls. Prior to immobilization, 10 knees were injected with high-molecular weight hyaluronic acid. The articular cartilage of the femoral condyles was studied by light microscopy, whereas that of the patella and tibia was analyzed biochemically. Degenerative changes of the articular cartilage similar to those seen in arthrosis were observed after 6 weeks. The intraarticular injection of hyaluronic acid did not prevent these changes; instead, the reparative processes seemed inhibited. PMID- 1909083 TI - Double-blind comparative multicentre study of fluvoxamine and mianserin in the treatment of major depressive episode in elderly people. AB - This is a multicentre double-blind study of fluvoxamine versus mianserin in the treatment of major depressive episode in patients over 65 years of age. Fifty seven patients received either fluvoxamine (100-200 mg daily) or mianserin (40-80 mg daily). There was no statistically significant difference in improvement between the 2 treatment groups as measured by the Montgomery-Asberg Depression Rating Scale. Eleven patients (7 in the fluvoxamine group and 4 in the mianserin group) discontinued treatment because of intolerance. No statistically significant differences were seen in biological parameters with either drug. Both drugs improved the symptoms of depression though the overall response rate was not outstanding. The side effects profile for the fluvoxamine was contrary to previous studies in that frequent nausea and vomiting were not seen. PMID- 1909084 TI - Resistance to the antiproliferative activity of IFN-alpha: further characterization and demonstration of antagonistic effects of IFN-gamma. AB - Mouse B16 melanoma cells have been shown to rapidly develop resistance to the antiproliferative effects of MuIFN-alpha or MuIFN-beta when exposed to these interferons. In cloning studies, the maximal antiproliferative effects of MuIFN alpha were seen with 2-4 days treatment. This resistance has been further characterized. The level of resistance which develops in B16 melanoma cells is dependent upon the concentration of MuIFN-alpha to which the cells are exposed. In addition, B16 melanoma cells which are resistant to the antiproliferative effects of MuIFN-alpha have greatly elevated levels of the interferon-induced enzyme 2',5'-oligoadenylate (2-5A) synthetase. Since it has previously been shown that B16 melanoma cells do not develop resistance to the antiproliferative effects of MuIFN-gamma, several experiments studied the influence of MuIFN-gamma on the development of resistance to MuIFN-alpha. Combinations of IFN-gamma and IFN-alpha have previously been shown to result in a synergistic enhancement of the antiproliferative effects. Kinetic studies show that the response of the cells to the MuIFN-gamma antiproliferative effect appears to be dominant over the development of resistance since no resistance develops in response to combination treatment. Not only is MuIFN-gamma able to prevent development of resistance when it is present continuously, but also when it is used for the sequential treatment of the cells before their exposure to MuIFN-alpha. A 2-day pretreatment with MuIFN-gamma is sufficient to prevent the development of resistance during later exposure of the cells to MuIFN-alpha alone for up to 6 additional days.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1909085 TI - A randomized, controlled trial of treatment of alcoholic hepatitis with parenteral nutrition and oxandrolone. I. Short-term effects on liver function. AB - The present studies were designed to provide careful measures of effects of oxandrolone, an anabolic steroid, intravenous nutritional supplementation, and the combination of these two treatments on liver functions, metabolic balances, nitrogen metabolism, and nutritional status in patients with moderate to severe alcoholic hepatitis. Of 43 patients originally recruited, 39 (19 men, 20 women) with typical clinical and laboratory features of alcoholic hepatitis (11 Child's Pugh class B; 28 class C) were admitted to a metabolic unit and completed a 35 day three-phase protocol. Phase I was a 10-day baseline period of observation, during which routine and special quantitative tests of liver function (galactose and antipyrine metabolism), a 7-day elemental balance study, and a 15N, 13C leucine metabolism study were done. Phase II was a 21-day treatment period during which patients were randomly assigned to receive one of four regimens: 1) standard therapy, consisting of abstinence, a balanced, nutritionally adequate diet, and multivitamins; 2) oxandrolone (20 mg orally four times a day) plus standard therapy; 3) nutritional supplementation, consisting of 2 L daily of 3.5% crystalline amino acids (in 5% dextrose), given by peripheral vein; or 4) a combination of oxandrolone and nutritional supplementation, along with standard therapy. Metabolic balances were repeated during phase II. Phase III was 2 or 3 days posttreatment, during which special studies of liver functions and volumes and leucine metabolism were repeated. All patients who completed phase I of study and were randomly allocated to one of the four treatment groups completed the subsequent two phases. Overall, with time, patients showed highly significant improvements in most clinical and laboratory features. For most standard laboratory tests (e.g., serum albumin, transferrin, prothrombin time) improvements were more marked in patients treated with nutritional supplementation and/or oxandrolone than in those given standard therapy alone. Liver volumes fell in all treatment groups, with greater improvement in those treated with nutritional supplementation. Improvements in galactose and antipyrine metabolism rates were significant only in those treated with nutritional supplementation or oxandrolone. Effects of treatments on metabolic balances, nitrogen metabolism, and measures of nutrition are described in this issue in a companion paper. We conclude that the addition of nutritional supplementation and oxandrolone to standard therapy of moderately severe or severe alcoholic hepatitis is well tolerated, and leads to more rapid improvement in the laboratory parameters measured. PMID- 1909087 TI - Prostaglandin analogues and reversal of hepatorenal syndrome: fact or fiction? PMID- 1909086 TI - A randomized, controlled trial of treatment of alcoholic hepatitis with parenteral nutrition and oxandrolone. II. Short-term effects on nitrogen metabolism, metabolic balance, and nutrition. AB - Patients with moderately severe or severe alcoholic hepatitis, described in a companion paper in this issue, had serial studies of energy and protein metabolism and elemental balances before and during treatment for 21 days with one of four randomly assigned regimens: 1) standard therapy, consisting of abstinence, a balanced, nutritionally adequate diet, and multivitamins; 2) oxandrolone (20 mg orally four times a day) plus standard therapy; 3) nutritional supplementation, consisting of 2 liters of 3.5% crystalline amino acids in 5% dextrose given by peripheral vein (PPN) plus standard therapy; and 4) a combination of the other three treatments. Dietary and intravenous intakes and weights were recorded daily, and weekly averages were calculated. Anthropometric measurements and blood studies were done weekly; blood studies included white blood cell counts and differentials, serum prealbumin, transferrin, and total protein and plasma aminograms. Four-days complete balance studies and measures of 15N,1-13C-leucine metabolism also were performed at baseline and after the treatment period. Major findings were as follows: a) Intakes of total calories and protein were significantly higher in PPN-treated than in other groups. b) All patients had positive elemental balances, both at baseline and at the end of the treatment period. However, those treated with PPN (with or without oxandrolone) had higher positive balances of nitrogen, potassium, phosphorus, and magnesium, indicating improvement in lean body mass. c) Anthropometric measurements showed no significant changes, but measures of the visceral protein compartment (serum prealbumin, transferrin, total protein, total lymphocyte count) improved significantly with time. For most of these variables, increases were significantly greater in those treated with PPN with or without oxandrolone than in the other groups. However, for prealbumin, the increase was greatest in the oxandrolone-treated group d) PPN treatment produced dramatic increases in levels of branched-chain amino acids and improvement in the ratio of plasma branched chain to aromatic amino acids. Other treatments had no effect on plasma aminograms. e) Metabolism of 15N,1-13C-leucine was normal and was not affected significantly by treatment. Therapy with PPN and/or oxandrolone was tolerated well. We conclude that PPN has favorable effects on energy and protein metabolism in florid alcoholic hepatitis; oxandrolone has lesser effects, although it may exert some additional action and particularly increases serum prealbumin levels. The results support the use of nutritional supplementation in therapy of moderately severe or severe alcoholic hepatitis. PMID- 1909088 TI - Association of Schistosoma mansoni with colonic carcinoma. PMID- 1909089 TI - GM1-gangliosidosis (genetic beta-galactosidase deficiency): identification of four mutations in different clinical phenotypes among Japanese patients. AB - GM1-gangliosidosis is a genetic neurological disorder caused by mutations in the lysosomal acid beta-galactosidase gene. While its phenotypic expression is complex, it is usually classified as being of infantile, juvenile, or adult form, on the basis of age at onset, the rate of symptomatic progression, and severity of central nervous system involvement. We have analyzed the acid beta galactosidase gene in 12 Japanese patients from nine families. The aim was to identify mutations in individual patients and then to examine possible correlation between the mutations and the clinical phenotypes. Northern blotting studies with a full-length human beta-galactosidase cDNA showed that the mRNA ranged from undetectable to substantially decreased in the infantile patients but was normal in quantity and size in all juvenile and adult patients. Four distinct missense mutations have been identified, each limited to the respective clinical forms within our small-size samples. In the infantile patient with decreased but detectable mRNA, a point mutation was found resulting in Arg49----Cys. In the infantile patient with nearly undetectable mRNA, mutation Arg457----Ter was identified. The mutation Arg201----Cys was found in all four of the juvenile patients, while all six adult patients were homozygous for the point mutation Ile51----Thr. The mutations found in the juvenile and adult patients alter restriction sites in the normal gene and thus are amendable to quick screening. The prediction that these mutations are responsible for the clinical disease was confirmed by no expression of the catalytic activity of the mutant proteins in the COS-I cell expression system.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1909091 TI - Competition in the home infusion industry. PMID- 1909092 TI - Drug-use evaluation of adult total parenteral nutrition using modified ASPEN guidelines. PMID- 1909090 TI - Gaucher disease: heterologous expression of two alleles associated with neuronopathic phenotypes. AB - To investigate the molecular basis for the distinct neuronopathic phenotypes of Gaucher disease, acid beta-glucosidases expressed from mutant DNAs in Gaucher disease type 2 (acute) and type 3 (subacute) patients were characterized in fibroblasts and with the baculovirus expression system in insect cells. Expression of the mutant DNA encoding a proline-for-leucine substitution at amino acid 444 (L444P) resulted in a catalytically defective, unstable acid beta glucosidase in either fibroblasts from L444P/L444P homozygotes or in insect cells. This mutation was found to be homoallelic in subacute neuronopathic (type 3) Gaucher disease. In comparison, expression of the mutant cDNA encoding an arginine-for-proline substitution at amino acid 415 (P415R) resulted in an inactive and unstable protein in insect cells. This allele was found only in a type 2 patient with the L444P/P415R genotype. The substantial variation in the type 3 phenotype (L444P homozygotes) suggests the complex nature of the molecular basis of phenotypic variation in Gaucher disease. Yet, the association of neuronopathic phenotypes with alleles producing severely compromised (L444P) or functionally null (P415R) enzymes indicates that the effective level of residual activity at the lysosome is likely to be a major determinant of the severity of Gaucher disease. PMID- 1909093 TI - Stability of ceftazidime and amino acids in parenteral nutrient solutions. AB - The stability of ceftazidime was studied under conditions simulating administration via a Y-injection site into a primary infusion of parenteral nutrient (PN) solution; the stabilities of ceftazidime and amino acids when the drug was added directly to PN solutions were also studied. Three PN solutions containing 25% dextrose were used; the amino acid contents were 0, 2.5%, and 5%. Ceftazidime with sodium carbonate was used to prepare stock solutions of ceftazidime 40 mg/mL in both 0.9% sodium chloride injection and 5% dextrose injection; to simulate Y-site injection, samples were added to the three PN solutions to achieve ceftazidime concentrations of 10 and 20 mg/mL, or 1:1 and 1:3 ratios of drug solution to PN solution. Samples of these admixtures were assayed by high-performance liquid chromatography (HPLC) initially and after room temperature (22 degrees C) storage for one and two hours. Additional solutions were prepared by adding sterile water for injection to ceftazidime with sodium carbonate; drug solutions were added to each PN solution in polyvinyl chloride bags to achieve ceftazidime concentrations of 1 and 6 mg/mL. The samples were assayed by HPLC for ceftazidime concentration after storage at 22 degrees C for 3, 6, 12, 24, and 36 hours and at 4 degrees C for 1, 3, 7, and 14 days. Amino acid stability was analyzed in admixtures containing 5% amino acids and ceftazidime 6 mg/mL after 24 and 48 hours at 22 degrees C and after 7 and 10 days at 4 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1909094 TI - Database program used by a home infusion therapy provider. PMID- 1909095 TI - Visual compatibility of ganciclovir sodium and total parenteral nutrient solution during simulated Y-site injection. PMID- 1909096 TI - The gastropulmonary route of infection--fact or fiction? AB - Published studies relating to whether medicinal stress-bleeding prophylaxis leading to an increase of gastric pH favors the development of bronchopulmonary infections are reviewed. Results from studies in healthy humans, patients with ulcer disease, and patients in the intensive care unit (ICU) clearly show that the risk of gastric bacterial colonization significantly increases relative to increasing gastric pH. Moreover, a drug-induced increase of gastric pH leads directly to gastric bacterial colonization also in patients in the ICU, above all with bacteria typical of the gastrointestinal tract. Comparing the different bacterial spectra of the oropharynx, stomach, and upper small intestine, it becomes clear that the stomach is a reservoir of bacteria independent of the oropharynx and also subject to retrograde colonization due to the duodenogastric reflux. Both by means of microbiological and in particular direct detection procedures, it can be demonstrated that in at least 30-40% of intubated patients a gastropulmonary route of colonization occurs. In patient groups without a medication-induced increase of gastric pH the number of bacteria detected in the tracheal secretion is about 33% less than in the case of conventional stress bleeding prophylaxis. These findings make it understandable that a highly significant increase in the pneumonia rate is seen in patients receiving pH increasing stress-bleeding prophylaxis versus control groups without therapy essentially influencing gastric pH. A risk score was developed that allows an easy description of those patients who are at an increased risk of pulmonary infections due to the gastropulmonary route of colonization. PMID- 1909098 TI - Ontogeny and evolution of pelvic diameters in anthropoid primates and in Australopithecus afarensis (AL 288-1). AB - Pelvic diameters (both anteroposterior [AP] and transverse [TR]) were investigated in a series of anthropoid primates. The ratio of diameters (AP/TR) in each of three pelvic planes (inlet, midpelvis, and outlet) was calculated. In addition to the above, the length of the iliac, pubic, and ischial axes and the angles between these axes were determined. The AP/TR ratio at the pelvic inlet is (reported in millimeters, +/- SD, unless otherwise specified) 1.81 +/- 0.27 in New World monkeys (Cebidae) and Macaca mulatta; 1.53 +/- 0.17 in hylobatids and pongids; 0.87 +/- 0.08 in Homo sapiens; and 0.58 in Australopithecus afarensis (AL 288-1). The AP/TR ratio in the midpelvis is 1.61 +/- 0.23 in nonhominid primates (Cebidae, M. mulatta, hylobatids, and pongids), 1.12 +/- 0.11 in humans, and 0.59 in AL 288-1. In monkeys (Cebidae and M. mulatta), hylobatids, pongids, H. sapiens, and AL 288-1, the ratios of the length of the pubic axis over the ischial axis were 0.84 +/- 0.06, 0.95 +/- 0.07, 1.10 +/- 0.15, and 1.46, respectively; the pubis-ilium angles were 96 +/- 11, 120 +/- 10, 131 +/- 11, and 147 degrees, respectively; and the ischium-pubis angles were 106 +/- 11, 86 +/- 8, 96 +/- 7, and 68 degrees, respectively. In none of these pelvic features was AL 288-1 "intermediate" between pongids and H. sapiens. The anatomical peculiarities of the pelvis in AL 288-1 are explained primarily as the result of early adaptation to erect posture, which resulted in the reduction of the distance between the sacroiliac joint and the hip joint. As a consequence, the sacral promontory moved toward the pubic symphysis, and this resulted in shortening of the AP diameter and widening of the TR diameter at the pelvic inlet. PMID- 1909097 TI - The effects of sucralfate and luminal stasis on recovery of the chambered rat gastric mucosa from taurocholate-induced damage. AB - We have previously shown, using a gastric chamber model, that both sucralfate and luminal stasis protected the rat gastric mucosa against the development of hemorrhagic erosions produced by subsequent exposure for 10 minutes to acidified (50 mM HCl) 80 mM sodium taurocholate (NaT). The protection afforded by sucralfate was abolished by inhibition of cyclooxygenase activity but restored by sucralfate. In this study we demonstrate that indomethacin pretreatment decreases both the depth (in microns) and magnitude (in pH units) of the juxtamucosal pH gradient, but that sucralfate restores these parameters to levels characteristic of normal mucosae. The cytoprotective effect of sucralfate is thus prostaglandin independent and, at least in part, a consequence of sucralfate-induced increases in the thickness of the juxtamucosal pH gradient/unstirred layer. We have also examined the ability of sucralfate to prevent the otherwise inevitable development of hemorrhagic erosions when it was applied after the gastric mucosa was exposed to NaT. When 100 mg sucralfate in 50 mM HCl was applied for 10 minutes, without stirring, subsequent to a 10-minute exposure of the mucosa to NaT, the average lesion area was reduced from about 15% to less than 3%. Unlike its cytoprotective property, the ability of sucralfate to accelerate the recovery process after damage was abolished by indomethacin pretreatment. Studies using antimony microelectrodes revealed that indomethacin pretreatment resulted in reductions in both the depth and magnitude of the pH gradient that resulted from plasma efflux from the mucosa after exposure to the acidified bile salt. These studies demonstrate that sucralfate is capable not only of prevention or attenuation of acute damage when administered prior to damaging agents, but is also capable of arresting the sequence of events that produces hemorrhage in the previously inflamed or damaged stomach. PMID- 1909099 TI - Mania and fluvoxamine. PMID- 1909100 TI - [Our experience in using the IP-2-50 infusion pump with newborn infants, pregnant women and puerperae]. AB - The authors describe indications for usage of venous administrations by means of the infusion pump IP 2-50 in newborns, pregnant women and parturients as well as during feeding of the smallest preterm infants with the same pump. Advantages and disadvantages of IP 2-50 are presented in comparison with the perfusion pumps "Braun Melsungen" and "Lineomat". Nosologic units are described, in which infusions with IP 2-50 are applied. PMID- 1909101 TI - [Recombinant tissue-type plasminogen activator for the emergency treatment of perioperative life-threatening pulmonary embolism (stage IV). Results in 7 patients]. AB - We report a series of seven patients (age: 43-77 years, preoperative American Society of Anesthesiologists (ASA) physical status II-III) with perioperative, life-threatening pulmonary embolism and severe cardiogenic shock treated with recombinant tissue type plasminogen activator (rt-PA). Diagnosis was established by ECG (n = 7), arterial blood gas analysis (n = 7), massive elevation of mean pulmonary arterial pressure (MPAP: 40 +/- 6 mmHg SD, n = 7), echocardiography (n = 3), increased arterial/end-tidal CO2 difference (30 +/- 16 mmHg, n = 3), and pulmonary angiography (n = 4). All patients had to be ventilated, six with an FIO2 of 1.0. To achieve a mean arterial pressure of above 60 mmHg all patients received norepinephrine 0.4 +/- 0.2 microgram.kg-1.min-1 in combination with dopamine 11 +/- 5 micrograms.kg-1.min-1 (n = 6), epinephrine 0.13 +/- 0.04 microgram.kg-1.min-1 (n = 5) or dobutamine 14 +/- 6 micrograms.kg-1.min-1 (n = 3). In addition, six of seven patients had to be resuscitated by external chest compression (duration of resuscitation: 5 to 40 min) prior to or during the thrombolytic therapy. The dosages of rt-PA ranged from 10 to 150 mg, and the duration of administration up to 31 h. Six patients survived neurologically intact. In these six patients MPAP had decreased from 41 +/- 6 mmHg to 33 +/- 6 mmHg (P less than 0.05, Wilcoxon rank test) 2 h after the start of thrombolytic therapy, with concomitant reduction of vasopressor and inotropic support.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1909102 TI - [Paralysis caused by carbohydrate during intensive care]. AB - In 30 septic, edematous intensive care patients a polyneuropathy occurred during treatment of peritonitis, pancreatitis, adult respiratory distress syndrome, or bronchopneumonia; 28 patients developed a complete tetraplegia. We believe this neuropathy to be an important cause of weaning failure. All patients had received parenteral or enteral nutrition with 240-800 g carbohydrate per day. Clinical data indicate that impairment of carbohydrate metabolism was the essential cause of the polyneuropathy. In 14 patients carbohydrate administration was continued; 13 died without neuromuscular recovery. In 16 patients carbohydrate nutrition was reduced to 100-250 g per day after the occurrence of tetraplegia; 13 of these made a full neurologic recovery. PMID- 1909103 TI - Effects of gamma radiation and azathioprine on Brucella abortus infection in BALB/c mice. AB - Sublethal irradiation of BALB/c mice 4 hours prior to inoculation with 5 x 10(4) virulent Brucella abortus, caused significant (P less than 0.01) reductions in bacterial numbers in comparison with numbers in unirradiated controls. Numbers of brucellae in the spleen were significantly lower by 5 days after inoculation and decreased thereafter, so that at 2 and 3 weeks after inoculation, there were up to 1,000-fold fewer organisms in the spleen of irradiated mice. The number of brucellae in the spleen increased in irradiated mice thereafter. The course of events in the liver was similar, but developed more slowly, and peak differences in bacterial numbers were about 1 log less. These phenomena were not attributable to differences in implantation of brucellae in the liver or spleen, nor to an abnormal distribution of organisms in other organs of irradiated mice. Irradiation of mice during the plateau phase of infection also resulted in significant (P less than 0.05) reductions in bacterial counts in the spleen during the succeeding 4 weeks. Macrophage activation in the spleen, measured by a Listeria monocytogenes-killing assay, was significantly (P less than 0.01) increased by irradiation alone at 1 week after inoculation and at that time was significantly (P less than 0.01) greater in B abortus-infected, irradiated mice than in B abortus-infected controls. Histologic, cytologic, and immunologic studies revealed that the decrease in numbers of organisms between 1 and 2 weeks after inoculation in irradiated mice occurred at a time when their immune response to B abortus was suppressed and when numbers of neutrophils and monocytes infiltrating the spleen were significantly (P less than 0.01) diminished.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1909104 TI - Effect of milk stasis on Brucella abortus infection of the mammary gland in goats. AB - To compare the effects of milk stasis and milk flow on Brucella abortus infection of the mammary gland under the same systemic conditions, primiparous goats (n = 5) were inoculated IV with B abortus on the day of parturition, and suckling by their neonates was restricted to one mammary gland. Goats were euthanatized and necropsied at 3 weeks after inoculation, and milk, mammary glands, and supramammary lymph nodes were evaluated by bacteriologic, histologic, and immunoenzymatic staining techniques. Nonnursed mammary glands had high titers of brucellae in milk, moderate interstitial mastitis, and brucellar antigen in macrophages located primarily in alveolar and ductal lumina. Brucellae often filled the macrophage cytoplasm. In contrast, nursed mammary glands had fewer brucellae in milk, minimal inflammatory changes, and no detectable brucellar antigen in histologic sections. Hyperplastic changes were only seen in supramammary lymph nodes draining nonnursed mammary glands; these contained more brucellae than lymph nodes draining nursed mammary glands. These studies show that milk stasis may be the sole cause of increased susceptibility of nonnursed mammary glands to B abortus infection. PMID- 1909105 TI - Clinical, clinicopathologic, and parasitologic observations of trypanosomiasis in dogs infected with North American Trypanosoma cruzi isolates. AB - Nineteen purebred Beagles of various ages (4, 5, 13, and 47 weeks) were inoculated with North American Trypanosoma cruzi isolates obtained from an opossum (Tc-O), an armadillo (Tc-A), or a dog (Tc-D). Dogs were grouped on the basis of clinical outcome of infection. During the acute stage of disease, dogs of group 1 (n = 7 inoculated with Tc-O or Tc-A) died or were euthanatized because of the severity of disease. Dogs of group 2 (n = 5 inoculated with Tc-O or Tc-A) developed acute disease, but survived to develop chronic disease. Dogs of group 3 (n = 7 Tc-D-inoculated dogs) developed neither acute nor chronic disease. Dogs of group 4 (n = 4--2 dogs 13 weeks old and 2 dogs 47 weeks old) served as noninoculated controls. Clinical signs associated with severe acute myocarditis developed in dogs of groups 1 and 2 between postinoculation day (PID) 15 and 28. Generalized lymphadenopathy and lymphocytosis were observed in all dogs of groups 1, 2, and 3 between PID 14 and 17. Serum alanine transaminase and aspartate transaminase activities and urea nitrogen concentration were high, and glucose concentration was low prior to death of dogs in group 1. Serum activities of isoenzymes of creatine kinase were significantly (P less than 0.05) high in only 1 dog (group 1), whereas serum lactate dehydrogenase isoenzyme activities were not significantly high in any dog.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1909106 TI - Fosvergnugen. The excitement of immediate-early genes. PMID- 1909107 TI - Use of the carbon dioxide laser in treating multiple cutaneous neurofibromas. AB - The CO2 laser is presented as a useful tool for the removal of large numbers of neurofibromas, the major source of cosmetic disfigurement in the patient with peripheral neurofibromatosis. Its advantages include high patient satisfaction with the rapid, staged removal of thousands of neurofibromas, with minimal morbidity and an enhanced appearance. The operative technique for each of the forms of neurofibroma, that is, pedunculated, sessile, and subcutaneous, is described. As with all procedures involving a change in appearance, it is essential that the patient be fully aware of the limitations of the procedure and the expected final result. This is easily accomplished in this procedure by the use of a "test treatment." PMID- 1909108 TI - Structure and function of signal-transducing GTP-binding proteins. PMID- 1909109 TI - New developments in the diagnosis of pediatric HIV infections. PMID- 1909110 TI - Bacterial interactions with chromate. AB - Hexavalent chromium compounds (chromates and dichromates) are highly toxic and are considered as mutagens and carcinogens. These compounds are discharged frequently to the environment as a result of diverse industrial processes. Some microorganisms are able to reduce hexavalent chromium to the less toxic trivalent form. Chromate pollution has promoted the selection of bacterial strains possessing chromate resistance determinants, usually carried by plasmids. Strains combining both abilities, i.e. resistance to and reduction of chromate, are potentially useful for detoxifying chromate polluted waste waters. PMID- 1909111 TI - Long-term outcome of lithium prophylaxis in bipolar patients. PMID- 1909112 TI - Purification and characterization of aspartate aminotransferase from the halophile archaebacterium Haloferax mediterranei. AB - Aspartate aminotransferase from the archaebacterium Haloferax mediterranei was purified and found to be homogeneous. An average Mr of 66,000 was estimated. The native halophilic transaminase exhibited no maximum absorption at 410 nm, which indicates that the apo form is obtained by our purification procedure, and the molar absorption coefficient at 275 nm in 3.5 M-KCl (pH 7.8) was found to be 78.34 mM-1.cm-1. Plots of titration data show that 1 mol of halophilic aspartate aminotransferase binds 2 mol of pyridoxal 5'-phosphate. The halophilic transaminase behaved as a dimer with two similar subunits and had a maximum activity in the pH range 7.6-7.9 and at 65 degrees C in 3.5 M-KCl. By differential scanning calorimetry, the denaturation temperature of the halophilic holo- and apo-transaminase was determined to be 78.5 and 68.0 degrees C respectively at 3.3 M-KCl (pH 7.8). At low salt concentration the halophilic transaminase was inactivated, following first-order kinetics. The Km values for 2 oxoglutarate and L-aspartate, in 3 M-KCl (pH 7.8), were 0.75 mM and 12.6 mM respectively. PMID- 1909113 TI - The purification of tissue inhibitor of metalloproteinases-2 from its 72 kDa progelatinase complex. Demonstration of the biochemical similarities of tissue inhibitor of metalloproteinases-2 and tissue inhibitor of metalloproteinases-1. AB - Human gingival fibroblasts in culture were shown to secrete a 72 kDa progelatinase, of which a proportion in the medium was found to be complexed with tissue inhibitor of metalloproteinases-2 (TIMP-2). A purification procedure was devised to purify free enzyme and inhibitor. We also describe the purification of both 95 kDa progelatinase bound to TIMP-1 and free 95 kDa progelatinase from the medium of U937 cells. A polyclonal antiserum to TIMP-2 was prepared and it was shown that TIMP-1 and TIMP-2 are antigenically distinct. The ability to form stable complexes and the relative inhibitory activities of TIMP-1 and TIMP-2 towards 95 kDa and 72 kDa gelatinases, collagenase, stromelysins 1 and 2 and punctuated metalloproteinase were determined; only minor differences were found. Complex-formation between TIMP-2 and 72 kDa progelatinase was demonstrated not to reduce the metalloproteinase-inhibitory activity of TIMP-2, a finding that led to the characterization of high-molecular-mass TIMP activity. Competition experiments between progelatinases and active gelatinases for TIMPs indicated that the affinity of TIMPs for progelatinases is weaker than that for active gelatinases. In a study of the effects of TIMP-1 and TIMP-2 on progelatinase self cleavage we found that both TIMP-1 and TIMP-2 inhibit the conversion of 95 kDa and 72 kDa progelatinases and prostromelysin into lower-molecular-mass forms. TIMP capable of complexing with progelatinase was shown to be no more efficient an inhibitor of gelatinase self-cleavage than TIMP not able to complex with progelatinase. PMID- 1909114 TI - Suppression of c-fos precursor RNA splicing by the protein kinase C inhibitor H7 [1-(5-isoquinolinesulphonyl)-2-methylpiperazine]. AB - In JB6 epidermal cells, induction of fos proto-oncogene expression by phorbol 12 myristate 13-acetate can be inhibited by the protein kinase C (PKC) inhibitor H7 [1-5(isoquinolinesulphonyl)-2-methylpiperazine]. The compound causes also a dose dependent suppression of fos precursor RNA splicing which, however, appears to react somewhat less sensitively to H7 than does PKC activity. This indicates that H7-induced accumulation of fos precursor RNA is not due to inhibition of PKC. Support for this interpretation comes from the finding that other inhibitors of PKC, such as N-(2-guanidinoethyl)-5-isoquinolinesulphonamide dihydrochloride, sphingosine, staurosporine or N-(6-aminohexyl)-5-chloro-1 naphthalenesulphonamide, do not suppress splicing when applied at PKC-inhibiting concentrations. PMID- 1909115 TI - Untreated type 1 diabetes does not impair adenosine-mediated inhibition of lipolysis in human adipocytes. PMID- 1909116 TI - Endotoxic lipid A induces intracellular Ca2+ increase in human platelets. AB - The activation of protein kinase C by endotoxic lipid A was observed with both intact platelets and in a cell-free system [Romano & Hawiger (1990) J. Biol. Chem. 265, 1765-1770]. We have now studied the action of lipid A on intracellular Ca2+ concentration ([Ca2+]i). Lipid A induced a concentration-dependent rise in [Ca2+]i in human platelets loaded with fura-2, which reached a maximum at 37.1 +/ 3.8 s (tmax). Maximum [Ca2+]i levels, observed at 30 microM lipid A, were 432 +/ 60 nM. EGTA (2 mM) or NiCl2 (1 mM) each decreased the lipid A-dependent elevation of [Ca2+]i by 50-60% without significant modification of tmax, but shortening the time for 50% recovery (t50) from greater than 400 s to 113.1 +/- 29.1 s and 54 +/- 2.1 s, respectively. Quenching of the fura-2 signal was also observed in lipid A-stimulated platelets resuspended with MnCl2 (1 mM), suggesting that both mobilization and external influx of Ca2+ occur. Intracellular Ca2+ mobilization depended on release from Ins(1,4,5)P3-sensitive stores, since Ins(1,4,5)P3 accumulation was detected in lipid A-activated platelets. Staurosporine, an inhibitor of protein kinase C, blocked the [Ca2+]i rise generated by lipid A in platelets [concn. giving 50% inhibition (IC50) = 0.1 microM], prolonging the tmax. to 54.7 +/- 5.1 s, but decreasing the t50 to 157.5 +/- 31.8 s. Staurosporine also suppressed InsP3 accumulation (IC50 = 0.15 microM). These results suggest that platelet activation by lipid A involves an interaction between [Ca2+]i elevation and protein kinase C activation. PMID- 1909118 TI - Mast cell exocytosis: evidence that granule proteoglycan processing is not coupled to degranulation. AB - It has been hypothesized that the dissolution of mast cell granules at the time of degranulation results from proteoglycan cleavage coupled to exocytosis. To address this hypothesis, we studied granule proteoglycan before and after exocytosis in dog mastocytoma cells, which solubilize granule contents during exocytosis. 35S-labeled proteoglycans were extracted from unstimulated whole cells and cell degranulation supernatant. Sequential anion-exchange and gel filtration chromatography, followed by specific glycosaminoglycan digestion, identified chondroitin sulfate and heparin glycosaminoglycan and proteoglycan in unstimulated cells and degranulated material alike. Glycosaminoglycan type and charge density in degranulation supernatant were unchanged compared with unstimulated cells. There was no decrease in proteoglycan size with cell activation and exocytosis. Thus, granule release and solubilization does not appear to require exocytosis-coupled degradation of granule proteoglycans. Release in association with high-m.w. proteoglycans may serve to limit rates of diffusion and activity of proteases and other mast cell mediators. PMID- 1909119 TI - Two receptor binding regions of human FSH show sense-antisense similarity to the human FSH receptor. AB - The sequences of two receptor binding regions of the beta-subunit of the human follicle-stimulating hormone (hFSH-beta) were compared with the DNA-derived antisense peptide sequence of the hFSH receptor. A striking sense-antisense similarity was established between these receptor binding regions and the hFSH receptor. Based on this sense-antisense similarity four putative hormone binding regions on the N-terminal extracellular region of the hFSH receptor are identified. PMID- 1909117 TI - Expression of a high-affinity form of UDP-glucuronosyltransferase in human foetal liver cells in culture on exposure to mercuric chloride. AB - The activity of UDP-glucuronosyltransferase (UDPGT, EC 2.4.1.17) in human foetal liver cells in culture was measured with two acceptor substrates, namely harmol and 1-naphthol. There was a dose-dependent increase of about 10-400% in UDPGT activity when the cells were exposed to 1-30 microM-HgCl2. Above a critical concentration of 30 microM-HgCl2, the heavy metal ion was toxic to the cells. Kinetic studies of the glucuronidation reaction with harmol and 1-naphthol showed that Hg2+ ions seemed to induce the expression of a high-affinity form of UDPGT, which was absent from the normal controls. The dramatic increase in specific activity in UDPGT was accompanied by a parallel increase in Vmax. measured with harmol and UDP-glucuronic acid. The significance of a possible induction of UDPGT in human foetal liver cells by HgCl2 is discussed. PMID- 1909120 TI - Evidence that the signal-initiating membrane protein CD9 is associated with small GTP-binding proteins. AB - F(ab')2 fragments of anti-CD9 mAb aggregate platelets by a thromboxane-dependent pathway implicating CD9 as signal initiating molecule. We demonstrate that mAbs directed against CD9, but not against GPIIb/IIIa specifically immunoprecipitate, from detergent lysates of human platelets, proteins of 25 and 26 kDa which bind [alpha 32P]GTP on nitrocellulose transfers. The binding is specific since it is blocked by GTP, but not by ATP. The GTP-binding proteins do not belong to a Mg(2+)-sensitive subset since they are unaffected by the addition of 2 microM-20 mM Mg2+. The observations demonstrate that CD9 is associated with selected small G-proteins. PMID- 1909121 TI - Cooperative effect of antisense-Rb and antisense-p53 oligomers on the extension of life span in human diploid fibroblasts, TIG-1. AB - Normal human diploid fibroblasts, TIG-1, which have a replicative life span of about 62 population doublings (PD), tended to senesce after about 50 PD with a gradual decrease in sensitivity to serum. Treatment of TIG-1 cells with the antisense-Rb oligomer, which completely depleted the retinoblastoma susceptibility gene product (RB), extended life span by about 10 PD. Treatment with the antisense-p53 oligomer alone had no effect; however, cotreatment with the antisense-Rb oligomer further potentiated the extension and the increased sensitivity to serum caused by the antisense-Rb oligomer alone, suggesting that p53 and RB function in separate, yet complementary pathways in signal transduction to senescence. The c-fos expression, which is presumed to be regulated negatively by RB, was not stimulated in partially senescent TIG-1 cells by treatment with the antisense-Rb oligomer. PMID- 1909122 TI - Energy transfer kinetics in C-phycocyanin from cyanobacterium Westiellopsis prolifica studied by pump-probe techniques. AB - The relaxation processes of C-phycocyanin at different aggregates have been investigated by pump-probe techniques. The lifetimes of ground state recovery measured at various wavelengths are analyzed by computer fitting of the kinetic data to a sum of three and four exponentials for monomers and trimers according to the nonlinear least-square principle, respectively. The shortest lifetime (about 56ps) is due to beta s----beta f transfer in one monomer, that decreases to 31ps in trimer due to the opening of new transfer channels. The second fastest component (about 151ps) in monomer is attributed tentatively to distribution of excitation energy between alpha and beta f chromophores, that decreases to about 117ps in trimer caused by redistribution of excitation energy between them. The two long-lived components (about 690ps and 1385ps for monomer, 620ps and 1320ps for trimer) from some kinds of heterogeneity in some chromophores, such as alpha and beta 1 chromophores which are emitting, show an equal amplitude ratio of 1:2 in both monomer and trimer. PMID- 1909123 TI - GM-CSF and IL-3 stimulate diacylglycerol generation in murine bone marrow-derived macrophages. AB - In murine bone marrow-derived macrophages, prelabeled with either [3H]myristic acid or [3H]arachidonic acid, the mitogenic colony stimulating factors GM-CSF and IL-3 stimulated a transient increase in [3H]diacylglycerol generation. Maximum [3H]diacylglycerol levels were detected at 10-15 min. The stimulation of [3H]diacylglycerol generation was dependent on the concentration of CSF and correlated with their ability to activate a variety of processes in the macrophage, including DNA synthesis. This is the first report to demonstrate that GM-CSF elevates diacylglycerol levels in macrophages and also to show that diacylglycerol generation may be an important signaling mechanism for IL-3 action. In conjunction with our recent demonstration that the mitogenic agents CSF-1, 12-0-tetradecanoylphorbol-13-acetate and exogenous phospholipase C also stimulate diacylglycerol generation in the macrophage (Veis and Hamilton, J.Cell.Physiol., 147, 298-305, 1991), our findings suggest that an increase in diacylglycerol levels is necessary but not sufficient for macrophage proliferation. PMID- 1909124 TI - Apoprotein A-1 is a cofactor independent substrate of protein kinase C. AB - Apoprotein A-1 (apo A-1), the predominant protein constituent of high density lipoproteins (HDL), was phosphorylated by protein kinase C (PKC). Optimal phosphorylation of lipid-free apo A-1 occurs in the absence of calcium, phosphatidyl serine (PS), and diolein (DO). However, HDL-bound apo A-1 was not phosphorylated by PKC. Furthermore, addition of either native or reconstituted HDL particles to lipid-free apo A-1 resulted in a concentration-dependent inhibition of phosphorylation. It appears that the phosphorylatable sites on apo A-1 are involved in hydrophobic interaction with the lipids of HDL. Apo A-1 is a novel substrate of PKC because it does not require calcium and lipid cofactors for optimal phosphorylation. PMID- 1909125 TI - An efficient method for constructing a chimeric bacteriophage T4 to estimate the regulatory signals. AB - A system for the quantitative estimation of T4 regulatory signals in bacteriophage T4 was developed. We constructed a transmitter-reporter [corrected] plasmid vector, pCV22, which is able not only to fuse transcriptional and translational signals to the coding region of lacZ gene (reporter) but also to transmit the fused gene into T4 phage genome (transmitter). The regulatory signals of T4 phage genes fused with the reporter gene was transmitted efficiently into T4 phage (T4dC-lac phage; a receiver phage) by a replacement type of recombination in the uvsY gene region. This type of chimeric phage was demonstrated to be able to quantitatively estimate the late regulatory signal of T4 phage in vivo. PMID- 1909126 TI - Hydrolysis of alanine oligomers and of elastin by P. aeruginosa proteinases and thermolysin. AB - The hydrolysis of alanine oligomers by P. aeruginosa proteinases, thermolysin and porcine pancreatic elastase was studied. The concentrations of substrates and cleavage products were determined using reverse phase high pressure liquid chromatography. Tetraalanine was the shortest oligomer for which we could demonstrate hydrolysis by all the proteinases, except for porcine pancreatic elastase which only significantly hydrolyzed peptides longer than hexaalanine. Porcine pancreatic elastase hydrolyzes hexaalanine at a single site, whereas the other enzymes may split it either into two trialanine molecules, or into di- and tetraalanine, the latter being further cleavable to dialanine. A kinetic model based on first-order kinetic rate constants is proposed and the individual constants determined. Although P. aeruginosa elastase and thermolysin are closely similar in structure, they have shown a marked difference in their hydrolysis of either elastin or tetraalanine. Elastolytic activity of thermolysin was higher than that of elastase but tetraalanine was hydrolyzed more slowly by thermolysin. PMID- 1909127 TI - Sequence and immunological characterisation of ovine pancreatic lipase. AB - Purified ovine pancreatic lipase has been subjected to a limited protein sequence analysis. Cyanogen bromide fragments from the molecule were isolated and characterised to enable the structure of the molecule to be mapped. Some tryptic peptides were also isolated, sequenced, and aligned by homology to lipase sequences from other species. A total of 172 residues out of a possible 456 have been assigned, including 45 residues at the N-terminus and 10 residues at the C terminus of the protein. A polyclonal antibody has been prepared to ovine lipase which has been characterised by Ouchterlony immunodiffusion and by Western blotting experiments. These experiments showed that the ovine pancreatic lipase was immunologically different from the ovine hepatic and lingual lipase, whereas there was considerable immunological similarity amongst ovine, bovine and rabbit pancreatic lipase, but less with porcine pancreatic lipase. PMID- 1909128 TI - Medicare moves toward bundled payments. PMID- 1909129 TI - A recruitment model for selecting residents. AB - The process of selecting residents is an important issue in medical training. In an attempt to quantify and thereby objectify this process, a model for selection was developed. The model, using scaled scores reflective of each of the applicants' characteristics, was used to rank applicants in the Department of Physical Medicine and Rehabilitation at the Medical College of Wisconsin, Milwaukee. Data derived from the selection process were analyzed over a three year period, 1986-1989. Statistical analysis of the data showed that as few as three experienced faculty members were needed to interview reliably. The statistically significant correlation (p less than .01) between those who interviewed and those who did not interview was necessarily influenced by the fact that those who did not interview had access to the narrative descriptors of those who did. These findings suggest that the use of this recruitment model would permit a more cost-effective approach to the selection of residents. PMID- 1909130 TI - The Health of the Public Program at the University of Washington: a new role for academic medical centers. AB - The University of Washington Health of the Public Program has convened a consortium composed of the region's academic medical center, the two largest managed care plans in Washington, and representatives of the state's major private and public purchasers of health care. The consortium's purpose is to test the feasibility of collaboratively collecting cross-system data, assessing variations in practice, and implementing site-specific interventions to improve the management of common illnesses and encourage preventive care. Changes under way in the ambulatory training environment and in the undergraduate curriculum as a result of the consortium's initial efforts are described. In today's climate of cost consciousness and concerns about quality, academic medical centers can play an important role in helping to improve community-wide outcomes of care. PMID- 1909131 TI - The relationship of residents' autonomy and use of a teaching hospital's resources. AB - This 1990 study examines the relationship between the degree of use of patient care resources and the degree of supervision of residents by attending physicians (as perceived by residents) at a large midwestern teaching hospital. Ratings of the degree of clinical autonomy allowed residents by 65 attending physicians- each of whom had a general internal medicine practice with a significant hospital component--were provided by 23 former internal medicine chief residents and 17 internal medicine residents who were in their third year at the time of the study. A regression model was used to test the association between hospital resource use (as shown by total hospital charges to patients and their lengths of stay) and the residents' mean ratings of the degrees of autonomy the attending physicians permitted residents, for 7,169 of these physicians' patients discharged between 1986 and 1989 in 28 diagnosis-related groups. The analysis was controlled for patients' insurance status and chronic disease comorbidities. The patients whose attending physicians were rated as allowing substantial clinical autonomy had significantly lower total charges and lengths of stay (p less than .0001). These results suggest that internal medicine residents have an inherently conservative practice style that values low-intensity workups and rapid discharge of patients. PMID- 1909132 TI - Formaldehyde-resistance in Enterobacteriaceae and Pseudomonas aeruginosa: identification of resistance genes by DNA-hybridization. AB - A 4.1. Kb large DNA fragment of a E. coli plasmid pVU 3695, on which the genes for formaldehyde-resistance are located, was used as a DNA probe to identify bacteria that carry this segment among formaldehyde-resistant bacteria. It was shown by Southern Blot-, Dot Blot-, and Colony Blot- Hybridization studies that the DNA of all formaldehyde-resistant E. coli, Serratia marcescens, Enterobacter cloacae, Citrobacter freundii and Klebsiella pneumoniae strains tested hybridize with the DNA probe from E. coli. In contrast the E. coli DNA probe does not hybridize with the DNA from formaldehyde-resistant Pseudomonas aeruginosa strains. PMID- 1909133 TI - [The activity of formaldehyde, glutardialdehyde, peracetic acid, chloramine T (N chlor-4-toluolsulfonamide), m-cresol, ethanol and benzyldimethyldodecylammonium bromide against bacteria which are found in coagulated blood. (Model studies for chemical disinfection of instruments]. AB - The experiments were performed using frosted glass as carrier with its surface being contaminated with whole blood containing Staphylococcus aureus as test organism. At the time of sampling, a heparin preparation was added to the blood to prevent premature coagulation. After addition of the staphylococci, coagulation was initiated by means of a heparin antagonist. 10, 25, 50, 100, and 150 microliters, respectively, of the blood were homogeneously spread on rectangular test areas of 10 x 20 mm. After the blood had coagulated, each of the test objects was placed in 15 ml of the solution (20 degrees C) containing the active ingredient tested for 60 min. After that, the test objects were removed from the disinfectant and, in order to inactivate any adhering active components, treated with a neutralizing solution of suitable composition. The number of viable germs (colony-forming units) was determined quantitatively. The blood samples were ground together with quartz sand. Aliquots of the diluted suspensions were mixed with molten agar medium. The plates then were incubated at 37 degrees C over a period of 14 days. The relative number of viable germs (N/No) per test object was calculated from the number of colonies. Plotting of the microbicidal effects obtained (log N/No] versus the concentration of the active substance (see Figs. 1-3) yielded curves differing in some characteristics as e.g. curvature, slope of the lower curve section (log N/No). less than -3), concentration range according to the layer thickness of the contamination. To visualize the reduction of the efficacy of the respective disinfectants caused by blood, the concentrations of active components were determined which are necessary to achieve a microbicidal effect of log (N/No) = -4. These concentrations were plotted versus the amounts of blood per test area (Fig. 4). The resulting curve for formaldehyde was slightly U-shaped. With a raising amount of blood, the concentration required slightly decreased in the beginning and increased again from an amount of ca. 100 microliter blood per test area. For all other active substances, the required concentration of these substances increased with the amount of blood used. The curve obtained for ethanol exhibited the lowest slope. The slope of the curves increased in the following order: ethanol, m-cresol, peracetic acid, chloramine T, glutardialdehyde, benzyldimethyldodecylammoniumbromide. The curves for chloramine T and glutardialdehyde nearly paralleled each other.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1909134 TI - Generation of Pseudomonas aeruginosa aerosols during handwashing from contaminated sink drains, transmission to hands of hospital personnel, and its prevention by use of a new heating device. AB - Pseudomonas aeruginosa was isolated from sinks of washing basins, showers, toilets and bathtubs, from the personnel and patients of a mixed infectious disease ward in a German children's hospital during a prospective 4-week epidemiological study. 81% of all sinks were contaminated with P. aeruginosa strains. Upon entering the hospital, all personnel hand cultures were P. aeruginosa-negative. However, during duty, 42.5% of the personnel members carried different P. aeruginosa strains on their hands. Detection of P. aeruginosa strains in sinks preceding the isolation of identical genotypes from personnel hands suggested a transmission route from sinks to hands. Opening of water taps generated aerosols containing P. aeruginosa sink organisms which contaminated hands during hand washing. Survival times of various P. aeruginosa strains in aerosols was dependent on strain characteristics, light and humidity, and t 1/2 differed between 3-76 min. Heating of washing basin sinks to 70 degrees C with a new, safe and inexpensive device inhibited bacterial growth in sinks, generation of P. aeruginosa aerosols, and resulted in hand cultures negative for P. aeruginosa after washing. PMID- 1909135 TI - Prevention of diabetes in NOD mice treated with antibody to murine IFN gamma. AB - The NOD mouse is studied as an animal model of human insulin-dependent diabetes mellitus (IDDM). To evaluate the role of IFN gamma in the pathogenesis of the disease, we have studied the effect of anti-IFN gamma mAb on the expression of insulitis and clinical diabetes. Treatment of mice with anti-IFN gamma mAb prevented the induction of early IDDM by cyclophosphamide as well as the adoptive transfer of diabetes by spleen cells from diabetic NOD mice. The protection against induction of diabetes by cyclophosphamide was observed in animals treated with the anti-IFN gamma mAb within 24 h following the first cyclophosphamide injection but not in animals in which mAb treatment was started 7 days later. Transfer of disease was prevented both in adult irradiated and in newborn recipients. The absence of clinical signs in these mice was corroborated by a significant reduction of both the extent and severity of insulitis. Over expression of Ia antigen on endothelial cells lining the islets was also considerably reduced in mice treated with mAb. These data strongly suggest a role for IFN gamma during the autoimmune process leading to beta cell destruction in diabetes and prompt further investigation of the use of such antibodies in the immunoprevention of IDDM. PMID- 1909136 TI - Reduction in insulitis following administration of IFN-gamma and TNF-alpha in the NOD mouse. AB - In insulin dependent diabetes mellitis (IDDM) beta cell destruction is associated with infiltration of the pancreatic islets by T lymphocytes and macrophages. Cytokine products from the infiltrating immunocytes not only have powerful immunoregulatory actions but also are capable of impairing islet cell functions and have thus been postulated to assume a central role in mediating anti-beta cell immunity and beta cell destruction. In an effort to explore further the role of cytokines in the pathogenesis of IDDM, we examined clinical, metabolic and pathological features of NOD/Wehi mice injected intraperitoneally with multiple doses of IFN-gamma and/or TNF-alpha. Blood glucose profiles were not significantly altered by injection of cytokines alone or in combination. Except for a hypoglycaemic rebound in mice injected with TNF-alpha, arginine stimulation tests revealed no disturbances in islet secretory function in cytokine injected mice. Compared with vehicle and cytokines alone, injection of IFN-gamma + TNF alpha was associated with a variety of clinical and pathological changes including abdominal distention, piloerection, ascites, oedema, thymic atrophy, splenic enlargement and pancreatic distention. Histological examination of the pancreas in these mice revealed moderate to severe pancreatitis which included focal haemorrhagic necrosis, oedema and polymorphonuclear and mononuclear cell infiltration. The islets in these mice appeared normal morphologically and when stained for insulin. The injection of IFN-gamma + TNF-alpha, and to a lesser extent TNF-alpha alone, was associated with a significant reduction in the severity of insulitis. Examination of pancreatic MHC-class I and class II molecule expression revealed in mice given IFN-gamma + TNF-alpha, as compared with controls, significant and uniform induction of both these molecules on ductal and acinar cells; low level MHC-class II expression was also detectable on beta cells in these mice. MHC-class I molecules which were expressed at high levels by beta cells in control mice did not appear to change following administration of the cytokines alone or in combination. We conclude that despite their immunostimulatory actions in vitro and in other models in vivo, systemic administration of the cytokines IFN-gamma and/or TNF-alpha to NOD/Wehi mice does not activate or enhance, and may actually suppress, anti-beta cell immunity in this model. PMID- 1909137 TI - Cytotoxic effect of IFN-gamma plus TNF-alpha on human islet cells. AB - We have previously reported that the combination of IFN-gamma plus TNF-alpha is able to induce the de novo expression of HLA class II on human beta cells. In the present study, we have investigated the effect of these cytokines, alone or in combination, on the function and viability of human islet cells in vitro. Three hour insulin release was markedly reduced in human islet monolayer cultures after 4 days' exposure to 1000 U/ml of the combination TNF-alpha plus IFN-gamma (36.7 +/- 7.7, % of the control +/- SEM) or to TNF-alpha alone (49.5 +/- 7% of the control) while IFN-gamma had little effect. On direct inspection cell damage was clearly detected only in the cultures treated with TNF-alpha plus IFN-gamma in which staining by indirect immunofluorescence (IFL) for insulin revealed that the number of beta cells was also significantly reduced, thus suggesting a real cytotoxic effect of this cytokine combination. This effect was not beta cell specific since glucagon release and the number of alpha cells were also reduced in the cultures exposed to IFN-gamma plus TNF-alpha. 51Cr release experiments supported the cytoxicity of these cytokines to normal islet cells. There was a time course relationship between class II induction (2 days) and the cytotoxic effect of IFN-gamma plus TNF-alpha (4 days) on the same islet cells. In conclusion, these results indicate that the combination of IFN-gamma and TNF alpha exerts a cytotoxic effect on human islet cells in vitro. PMID- 1909138 TI - [Microwave processing method of semen Armeniacae Amarum]. AB - This paper reports the microwave processing method of Semen Armeniacae Amarum (Prunus armeniaca var. ansu). The experimental results showed that amygdalase was completely inactivated and the contents of amygdaloside were not reduced at all. The time and temperature of the processing method have also been studied. PMID- 1909139 TI - Influence of interleukin-2 on the differentiation of macrophages. AB - Macrophage precursor cells, enriched in the light fraction of murine bone marrow, were cultured in vitro under the influence of CSF-1 or IL-2 or both cytokines. In the presence of CSF-1 or CSF-1 and IL-2 strong proliferation occurred, whereas in the presence of only IL-2 or medium, cells did not proliferate. Thus all proliferating cells had CSF-1 receptors and thus belonged to the macrophage lineage. IL-2 induced in these cells the formation of cytoplasmic granules and concomitantly NK-like lytic activity. Under high dosage IL-2 cells further differentiated into cells containing abundant amounts of cytoplasmic granules and exerted LAK type cytotoxicity. When IL-2 was withdrawn from the culture medium, cells could be redirected to develop the properties of typical macrophages when CSF-1 was present. Thus the composition of the cytokines surrounding macrophage precursors decides on their differentiation pathway. PMID- 1909140 TI - New insights into the immunopathology of tuberculosis. AB - Tuberculosis is characterised by fever, weight loss and necrosis in both lesions and tuberculin skin test sites (Koch phenomenon), although the antigens of Mycobacterium tuberculosis are not directly toxic to the tissues. The tissue damage appears to be due to several interacting factors. First, M. tuberculosis induces an immunoregulatory disorder of which a raised percentage of agalactosyl IgG is a marker. This is seen also in rheumatoid arthritis and Crohn's disease and is associated with tissue-damaging inflammation. Subsequently, several properties of M. tuberculosis exacerbate this disorder by triggering cytokine release, and rendering tissues sensitive to the toxicity of tumor necrosis factor (TNF). Moreover, M. tuberculosis, but not bacillus Calmette-Guerin or several Mycobacterium avium strains, produces a factor which increases the toxicity of TNF for individual cells. Thus, M. tuberculosis may distort the normal protective role of TNF so that this cytokine becomes toxic to the host. The immunoregulatory disorder associated with agalactosyl IgG appears to be susceptible to immunotherapy, so novel types of treatment for the immunopathological component of tuberculosis are being explored. PMID- 1909141 TI - Tumor necrosis factor-alpha: central regulatory cytokine in the induction of macrophage antimicrobial activities. AB - Expression of activated macrophage resistance to infection requires the cooperative interaction of interferon-gamma (IFN-gamma) and either interleukin-2 (IL-2), interleukin-4 or granulocyte/macrophage-colony-stimulating factor: no single cytokine is effective. For IFN-gamma and IL-2, the effector activity can be suppressed by the presence of anti-tumor necrosis factor-alpha (TNF-alpha) antibodies in the reaction mixture. IFN-gamma and IL-2, only in combination, induce TNF-alpha-specific mRNA and secretion of this cytokine by macrophages. Development of intracellular killing activity by activated macrophages also requires the autocrine effects of TNF-alpha. IFN-gamma provides the first signal for the production of nitric oxide (NO), the effector molecule for intracellular destruction of parasites. When IFN-gamma-treated cells are infected with pathogens, they are stimulated to make TNF-alpha. Expression of intracellular killing, as well as production of NO, is inhibited by anti-TNF-alpha antibody. PMID- 1909142 TI - Microbicidal activities of Salmonella typhimurium- and interferon-gamma-activated mouse peritoneal macrophages. AB - Activation of mouse peritoneal macrophages during infection of mice by various facultative intracellular bacteria and after intravenous injection of recombinant interferon-gamma (rIFN-gamma) was studied. Macrophage activation was demonstrated on the basis of three different criteria, i.e. inhibition of Toxoplasma gondii proliferation, enhanced release of H2O2 and increased expression of Ia antigen. Macrophages activated during an infection with Salmonella typhimurium showed no enhanced salmonellacidal or listericidal activity relative to control macrophages, whereas Listeria-activated macrophages killed Listeria but not Salmonella faster than control macrophages. The rate of proliferation of Salmonella in spleen and liver of activated mice was comparable to the proliferation in the organs of control mice. rIFN-gamma-activated macrophages displayed neither an enhanced salmonellacidal nor an enhanced listericidal activity. When high numbers of Listeria were injected intravenously the proliferation in spleen and liver of rIFN-gamma-treated and control mice was similar. The proliferation of Listeria in the liver of rIFN-gamma-treated mice was less than in control mice when 1 LD50 or lower numbers of bacteria were injected. It is concluded that peritoneal macrophages become activated during infections of mice with various intracellular pathogens. However, these activated macrophages do not show enhanced bactericidal activity against all bacteria. Furthermore, rIFN-gamma is not sufficient to enhance the listericidal activity of macrophages. PMID- 1909143 TI - Formation of interferon-gamma and tumor necrosis factor in mice during Salmonella typhimurium infection. AB - Formation of interferon-gamma (IFN-gamma) and tumor necrosis factor (TNF) during Salmonella typhimurium infection was investigated in lipopolysaccharide (LPS) sensitive C3H/HeN and C57BL/10ScSn(B10ScSn), and LPS-resistant (lpsd mutant) C3H/HeJ and C57BL/10ScCr(B10ScCr) mice. When infected with 50 colony-forming units (CFU) of S. typhimurium C5, C3H/HeN and B10ScSn mice became hypersensitive to the lethal effect of LPS. In the case of lpsd mutants, only C3H/HeJ mice became hypersensitive to LPS, while B10ScCr mice remained resistant. C3H/HeJ as well as B10ScSn mice produced significant amounts of plasma IFN-gamma on day 3 after infection. By this time bacterial CFU in the liver of B10ScSn and C3H/HeJ mice were 10(6.7) and 10(7.1), respectively. In B10ScCr mice, however, IFN-gamma was not detectable although bacteria present in the liver exceeded 10(8) CFU. On the other hand, plasma TNF was not detectable in any of the mouse strains during S. typhimurium infection. When S. typhimurium-infected mice were challenged with LPS on day 3, significant amounts of plasma TNF were measured in C3H/HeN and B10ScSn mice, while in the lpsd mutant C3H/HeJ and B10ScCr mice plasma TNF was undetectable. PMID- 1909144 TI - Secretory repertoire of HIV-infected human monocytes/macrophages. AB - Apart from lymphocytes, mononuclear phagocytes play an essential role as target cells for human immunodeficiency virus (HIV). Circulating blood monocytes (MOs) and tissue macrophages (M phi) may harbor and distribute the virus throughout the body. In addition, proinflammatory monokines [interleukin-1 (IL-1), IL-6, IL-8, tumor necrosis factor-alpha (TNF-alpha)] may contribute to the pathogenesis of HIV-mediated diseases. We have established a culture system on hydrophobic Teflon membranes for blood-borne MOs/M phi. Both freshly isolated MOs as well as MO derived M phi could be infected with a monocytotropic HIV-1 isolate (HIV 1D117III) derived from a perinatally infected child. The virus production monitored by assay for viral antigen in cell-free supernatant is continuous for several weeks. We analyzed the stimulus response and the secretory repertoire of MOs/M phi early after infection with HIV as well as in long-term cultured, virus replicating cells. Infected MOs/M phi respond to interferon-gamma more effectively than control cells as estimated from the release of neopterin. The response to lipopolysaccharide was regulated differently: whereas the proinflammatory cytokines IL-1, IL-6, IL-8 and TNF-alpha were up-regulated and even constitutively secreted upon infection, the production of the hematopoietin macrophage-colony-stimulating factor decreased. High levels of TNF-alpha and IL-1 might augment the infectibility of M phi by HIV in an autocrine manner. Our results may provide some explanation for the immunologic dysfunction, the hematopoietic failure and the chronic inflammatory disease occurring in HIV infected patients. PMID- 1909145 TI - Quantitative assessment of HIV-1 DNA load by coamplification of HIV-1 gag and HLA DQ-alpha genes. AB - We developed an assay for simultaneous amplification, detection and quantitation of HIV-1 gag gene and the DQ-alpha locus of the histocompatibility (HLA) region of the human genome by polymerase chain reaction (PCR). Crude cell lysates from control cell lines and peripheral blood mononuclear cells (PBMC) from HIV-1 infected and control individuals were coamplified using optimized concentrations of primers directed at both loci, followed by simultaneous hybridization with radioactively labeled HIV-1-gag and HLA-DQ-alpha probes. Simultaneous quantitation of the 242-base-pair HLA and 115-base-pair HIV products was accomplished by both end-point dilution analysis and image analysis of autoradiographs relative to standard curves derived from infected cell lines. We observed good agreement between input cell counts on fresh samples and the HLA-DQ alpha target copy number values determined by both end-point dilution analysis and comparison of band intensities with standard curves. HIV-1 proviral load in symptomatic patients ranged from 200 to 4000 HIV-PCR-units per 1 x 10(6) PBMC (mean of 1245 copies), whereas asymptomatic patients had levels ranging from two to 1000 HIV-PCR-units per 1 x 10(6) PBMC (mean of 213 copies). This HIV/HLA coamplification approach should be particularly useful for analysis of frozen repository samples from natural history studies, and may facilitate wider application of quantitative PCR analysis. PMID- 1909147 TI - A quartz crystal viscosity sensor for monitoring coagulation reaction and its application to a multichannel coagulation detector. AB - A quartz crystal viscosity sensor was applied to a coagulation reaction monitoring system. The system consists of 16 oscillating circuits, a channel selector, a frequency counter, a temperature controller and a microcomputer. The system is named the Quartz Chemical Analyzer (QCA). AT-cut quartz crystals (9 MHz) were used as viscosity detectors and were attached to a cell in order to expose only one side of the quartz plate. The system was applied to the detection of the blood coagulation factors VIII (F VIII) and IX (F IX). The activity of these factors was assayed by a single-stage method. A linear relationship was obtained in a double-logarithmic diagram of concentration versus coagulation time with respect to F VIII and F IX in the range 0.05-0.4 unit cm-3 and 0.025-0.2 unit cm-3, respectively. PMID- 1909146 TI - Zidovudine therapy associated with remission of chronic active hepatitis C in HIV 1 carriers. PMID- 1909148 TI - The Ras superfamilies: regulatory proteins and post-translational modifications. AB - The Ras-like GTP-binding proteins comprise a large superfamily of proteins that play key roles in a wide variety of cellular activities, including cell growth, differentiation, secretion, and protein trafficking. During the past few years, it has become clear that these GTP-binding proteins are regulated by a variety of manners, including interactions with specific types of regulatory proteins and post-translational modification events. PMID- 1909149 TI - Cell regulation. PMID- 1909150 TI - Citrulline-malate effect on microsome phospholipids and cytochrome P450 in Euglena grown with ethanol. AB - This study indicates for the first time the presence of cytochrome P450 in the microsomes of Euglena grown in lactate medium and substantiates the use of Euglena as a hepatic cell model. Similar effects of ethanol on Euglena and on rat hepatic microsomes were demonstrated: (i) decrements in the quantities of FA per milligram of proteins; (ii) increases in the proportions of PE; (iii) decreases in the proportions of PC; and (iv) production of cytochrome P450, degraded in P420. The citrulline-malate reestablishes in the microsomes the phospholipid environment and the cytochrome P450 concentration. These findings illustrate that the complex acts on the lipid peroxidation via the changes in cytochrome P450 activity. PMID- 1909151 TI - A pilot study of the efficacy and safety of bolus administration of alteplase in acute myocardial infarction. AB - OBJECTIVE: To examine the efficacy, safety, and the pharmacokinetic profile of a bolus dose administration regimen of alteplase in the treatment of acute myocardial infarction. DESIGN: An open pilot study. SETTING: District general hospital. PATIENTS: 33 suitable consecutive patients presenting within six hours of the onset of symptoms who satisfied the electrocardiographic criteria for acute myocardial infarction. INTERVENTIONS: Two intravenous boluses of 35 mg alteplase, 30 minutes apart. MAIN OUTCOME MEASURES: Angiographic coronary patency at 90 minutes and 24 hours. Plasma alteplase concentration-time profile and pharmacokinetic analysis. RESULTS: Coronary patency at 90 minutes: 26 of 30 arteries (87%, 95% confidence interval (CI) 74-99%). Coronary patency at 24 hours: 24 of 29 arteries (83%, CI 69-97%). Mean (SD) plasma tissue plasminogen activator (t-PA) concentration reached 4434.8 (2117.8) and 4233.3 (2217.5) ng/ml within 10 minutes of each bolus and fell to 425.8 (288.3) ng/ml between boluses. The estimated peak concentrations at two minutes after boluses were 12,389 (8580) ng/ml and 10,811 (6802) ng/ml. The derived pharmacokinetic variables were volume of distribution 3.11 (1.89) 1, clearance 21.3 (9.3) 1/h, half life 5.9 (1.7) minutes. CONCLUSIONS: This simple administration regimen achieved brief, high concentrations of plasma t-PA that were well tolerated. The regimen was associated with a high coronary patency rate at 90 minutes that was well maintained at 24 hours. PMID- 1909153 TI - Small GTP-binding proteins of the ras family: a conserved functional mechanism? AB - Mutated ras genes can acquire a transforming potential and are frequently detected in human tumors. The mammalian ras gene family includes at least 35 distinct members that can be divided into three main groups on the basis of their sequence similarity to ras, rho, or rab genes. All these genes encode small GTP binding proteins. Rho proteins are implicated in actin organization and control of cell shape, probably by interacting with the cytoskeleton and intracellular membranes. Rab proteins are involved in vesicular traffic, and appear to control the translocation of vesicles from donor to acceptor membranes. The precise function of ras proteins is unknown, although the prevailing view is that they act as transducers of mitogenic signals. We propose that ras proteins, by analogy with rho and rab, are involved in the lateral segregation of multi-protein complexes at the plasma membrane, and we suggest how this process may be important for mitogenic signal transduction. PMID- 1909152 TI - Avoidance of tolerance and lack of rebound with intermittent dose titrated transdermal glyceryl trinitrate. The Transdermal Nitrate Investigators. AB - OBJECTIVES: To investigate the efficacy of transdermal glyceryl trinitrate given continuously and with a nocturnal nitrate free period. DESIGN: Double blind placebo controlled study with two parallel limbs. SETTING: Multicentre trial. PATIENTS: 52 patients randomised to receive either continuous treatment (23 patients) or intermittent treatment with an individually titrated dose (29 patients) for 14 days: both treatments were compared with placebo in a cross-over fashion. INTERVENTION: Continuous treatment with 10 mg per 24 hours of transdermal glyceryl trinitrate or intermittent transdermal glyceryl trinitrate titrated to give an arbitrary 10 mm Hg drop in systolic blood pressure (mean dose 18.2 mg) given over approximately 16 hours. MAIN OUTCOME MEASURE: Treadmill exercise stress testing and ambulatory monitoring of the ST segment after 14 days' treatment. RESULTS: After 14 days' intermittent treatment resting supine and standing systolic blood pressure fell by 7.5 mm Hg (95% confidence interval 2.7 to 12.2) and 9.0 mm Hg (95% CI 3.4 to 14.5) respectively (p less than 0.01); resting heart rate was unchanged. Mean heart rate at 1 mm ST segment depression rose by 11.9 beats/min (CI 1.1 to 23.7) (p less than 0.05), mean time to onset of angina increased by 59 seconds (CI 10.8 to 108) (p less than 0.05), and total exercise duration increased by 40 seconds (p less than 0.05). These changes were not seen after continuous treatment. The frequency of ischaemic episodes was not reduced with either regimen nor was the circadian distribution of these episodes altered, in particular nocturnal episodes did not increase during intermittent treatment. CONCLUSION: Tolerance to glyceryl trinitrate was avoided by the use of individually titrated doses administered with a nocturnal nitrate free period. There was no evidence of "rebound" on ambulatory monitoring during this treatment. PMID- 1909154 TI - The neurofibromatosis genes: from molecular cloning to cellular function. PMID- 1909155 TI - Therapy with and mechanisms of nonsteroidal anti-inflammatory drugs. AB - Nonsteroidal anti-inflammatory drugs have anti-inflammatory, analgesic, and antipyretic properties. Although most nonsteroidal anti-inflammatory drugs inhibit prostaglandin synthesis, these agents also have important pharmacologic actions unrelated to their effects on prostaglandins. Among these properties is the ability to inhibit the release of mediators of inflammation from neutrophils and macrophages. These effects are due to the ability of nonsteroidal anti inflammatory drugs to intercalate into the lipid bilayer of the plasma membrane and thereby disrupt protein-protein and protein-lipid interactions critical for cell responses (eg, calcium translocations, membrane phospholipid turnover). Our data, for example, indicate that nonsteroidal anti-inflammatory drugs exert direct inhibitory actions at the regulatory GTP protein (G protein) within the plasma membrane. This exhibit examines the evidence for diverse mechanisms of action of nonsteroidal anti-inflammatory drugs including effects directed at the G protein as well as new evidence that nonsteroidal anti-inflammatory drugs regulate the expression of the cyclooxygenase enzyme at the level of gene transcription. PMID- 1909156 TI - Animal models of rheumatoid arthritis. AB - Experimental animal models of arthritis, including type II collagen-induced arthritis, proteoglycan-induced arthritis, adjuvant arthritis, pristane-induced arthritis, and streptococcal cell wall-induced arthritis have contributed to recent advances in the understanding of the immunopathology of arthritis. The dissection of the T-cell populations regulating the autoimmune response is currently the most active area of investigation. Research into the mechanism underlying the association of specific class II major histocompatibility complex antigens with arthritis has focused attention on the interaction of particular V beta T-cell subsets with antigens presented in context of permissive major histocompatibility complex antigens. Several models indicate that both the structure of the major histocompatibility complex antigen and the T-cell receptor may be critical in the development of autoimmunity, while the MIs antigen system appears to regulate the availability of T cells with self-reactivity specificities. Studies on the role of heat-shock proteins in experimental arthritis have prompted research into the role of gamma/delta T cells in joint disease, while the availability of recombinant cytokines has permitted the direct analysis of soluble factors. In addition to providing basic insights into autoimmune disease, animal models continue to provide the means to test novel experimental approaches to the treatment of rheumatoid arthritis. PMID- 1909157 TI - Excellence in contemporary clinical nursing. PMID- 1909158 TI - Focus on East Anglia. Learning bullseye. Interview by Linda Thomas. PMID- 1909159 TI - World Student Games: college of steel. PMID- 1909160 TI - Nurse agencies: coming up roses. Interview by Norah Casey. PMID- 1909161 TI - Therapeutic touch and massage. PMID- 1909162 TI - Breast screening: benign breast disease and disorders. PMID- 1909163 TI - Educating the consumer and client. PMID- 1909164 TI - Psychiatric care for black patients. PMID- 1909165 TI - Home hindrance? PMID- 1909166 TI - Career development: what sociology offers. PMID- 1909167 TI - Towards enlightenment. PMID- 1909168 TI - Crisis in Bulgaria. PMID- 1909169 TI - Who are we? PMID- 1909170 TI - Stop taking the medicine? PMID- 1909171 TI - Mentorship: not mentor be. PMID- 1909172 TI - Prolonged depolarization in rods in situ. AB - Intracellular recordings were made from rods in the superfused retina of the marine toad (Bufo marinus). It was found that injection of a brief depolarizing current pulse (0.04-1 nA) evoked a distinctive, long-lasting response, here called "the prolonged depolarization." The response appears to be regenerative, has a stereotypical waveform, is typically about 6 mV in amplitude and 3 s in duration, and has a relatively long recovery period (10-60 s). As a rule, the response cannot be directly evoked by light but the current-evoked response is significantly enhanced in the presence of steady illumination. The light-evoked hyperpolarization and the depolarizing spikes of the rod are both attenuated in the presence of the prolonged depolarization. The prolonged depolarization is not an altered manifestation of the depolarizing spikes of toad rods since both can be recorded simultaneously and steady illumination suppresses the spikes while enhancing the prolonged depolarization. The response is enhanced in chloride-free superfusate and also appears to be enhanced by the use of electrodes containing chloride. The response is markedly shortened in superfusates that lack calcium or contain 1-5 mM cobalt. On this and other evidence, it is suggested that the response may be generated by the sequential action of calcium channels and calcium-activated chloride channels. Although rarely evoked by light, the prolonged depolarization of toad rods is otherwise remarkably similar to the prolonged depolarization of turtle cones. It is proposed that the prolonged depolarization, in contrast to the feedback depolarization of cones, arises from mechanisms common to both rods and cones. PMID- 1909173 TI - The measurement of end tidal carbon dioxide concentrations using modified nasal prongs in ophthalmologic patients under regional anesthesia. PMID- 1909174 TI - Serum response factor affects preinitiation complex formation by TFIID in vitro. AB - Serum response factor (SRF), a transcription factor that binds to the serum response element (SRE) of the c-fos proto-oncogene, activates transcription of an SRE-containing reporter plasmid in vitro. We describe here preincubation experiments which indicate that SRF activates transcription by facilitating the formation of active preinitiation complexes. Full activation by SRF occurred if SRF was preincubated with the general transcription factors. However, if the general transcription factors were preincubated and SRF was added subsequently, only poor activation of transcription was observed. This suggests that SRF must be present during preinitiation complex formation and that this complex is refractory to activation if SRF is absent during its formation. We have fractionated the general transcription factors and found that only a highly purified fraction containing the TATA-binding factor TFIID (and other unidentified components) must be present during preincubation for maximal transcriptional induction by SRF. This supports a model in which SRF activates transcription by affecting the conformation of TFIID bound to the promoter. Also of interest was the finding that recombinant human TFIID expressed in bacteria cannot mediate SRF-activated transcription, although it does support basal transcription. These results suggest that SRF may affect TFIID via a cofactor or coactivator. PMID- 1909175 TI - Rotation and interactions of genetically expressed cytochrome P-450IA1 and NADPH cytochrome P-450 reductase in yeast microsomes. AB - Rat liver cytochrome P-450IA1 and/or yeast NADPH-cytochrome P-450 reductase was expressed genetically in yeast microsomes. The ratio of P-450IA1 to the reductase was about 17:1 and 1:2 without and with coexpression of the reductase, respectively. Rotational diffusion of P-450IA1 was examined by observing the flash-induced absorption anisotropy, r(t), of the heme.CO complex. In only P 450IA1-expressed microsomes, 28% of P-450IA1 was rotating with a rotational relaxation time (phi) of about 1200 microseconds. The mobile population was increased to 43% by the presence of the coexpressed reductase, while phi was not changed significantly. Increased concentration of KCl from 0 to 1000 mM caused considerable mobilization of P-450IA1. The results demonstrate a proper incorporation of P-450IA1 molecules into yeast microsomal membranes. The significant mobilization of P-450IA1 by the presence of reductase suggests a possible transient association of P-450IA1 with the reductase. PMID- 1909176 TI - Catalytic enhancement of human carbonic anhydrase III by replacement of phenylalanine-198 with leucine. AB - Carbonic anhydrase III, a cytosolic enzyme found predominantly in skeletal muscle, has a turnover rate for CO2 hydration 500-fold lower and a KI for inhibition by acetazolamide 700-fold higher (at pH 7.2) than those of red cell carbonic anhydrase II. Mutants of human carbonic anhydrase III were made by replacing three residues near the active site with amino acids known to be at the corresponding positions in isozyme II (Lys-64----His, Arg-67----Asn, and Phe-198- --Leu). Catalytic properties were measured by stopped-flow spectrophotometry and 18O exchange between CO2 and water using mass spectrometry. The triple mutant of isozyme III had a turnover rate for CO2 hydration 500-fold higher than wild-type carbonic anhydrase III. The binding constants, KI, for sulfonamide inhibitors of the mutants containing Leu-198 were comparable to those of carbonic anhydrase II. The mutations at residues 64, 67, and 198 were catalytically independent; the lowered energy barrier for the triple mutant was the sum of the energy changes for each of the single mutants. Moreover, the triple mutant of isozyme III catalyzed the hydrolysis of 4-nitrophenyl acetate with a specific activity and pH dependence similar to those of isozyme II. Phe-198 is thus a major contributor to the low CO2 hydration activity, the weak binding of acetazolamide, and the low pKa of the zinc-bound water in carbonic anhydrase III. Intramolecular proton transfer involving His-64 was necessary for maximal turnover. PMID- 1909177 TI - Rational design of quinazoline-based irreversible inhibitors of human erythrocyte purine nucleoside phosphorylase. AB - Described herein is the rational design of irreversible inhibitors of human erythrocyte purine nucleoside phosphorylase (PNPase). Inhibitor design started with the observation that the amino group of 8-aminoquinazolin-4(3H)-one interacts with enzyme-bound phosphate. This observation correctly predicted that the 5,8-dione (quinone) and 5,8-dihydroxy (hydroquinone) derivatives of quinazolin-4(3H)-ones would enter the active site. The amine-phosphate interaction also served to confirm that a quinazolin-4(3H)-one binds in the PNPase active sites like a purine substrate. From models of the PNPase active site it was possible to design quinazoline-based quinones that undergo a reductive-addition reaction with an active-site glutamate residue. The best inhibitor studied, 2-(chloromethyl)quinazoline-4,5,8(3H)-trione, rapidly inactivates PNPase by a first-order process with an inhibitor to enzyme stoichiometry of 150. The active-site hydroquinone adduct of this inhibitor eliminates a leaving group to afford a quinone methide species positioned to alkylate another active-site glutamate residue. Thus, this inhibitor is designed to cross-link the PNPase active site by reductive addition followed by the generation of an alkylating quinone methide species. PMID- 1909178 TI - Arginine residues in the D2 polypeptide may stabilize bicarbonate binding in photosystem II of Synechocystis sp. PCC. AB - Bicarbonate (HCO3-) causes a significant and reversible stimulation of anion inhibited electron flow in photosystem II of higher plants and cyanobacteria. To test if selected arginine (Arg) residues are involved in the binding of HCO3-, we utilized oligonucleotide-directed mutagenesis to construct Synechocystis sp. PCC 6803 mutants carrying mutations in Arg residues in the D2 protein. Measurements of oxygen evolution showed that the D2 mutants R233Q (arginine-233----glutamine) and R251S (arginine-251----serine) were 10-fold more sensitive to formate than the wild type. The formate concentration giving half-maximal inhibition of the steady-state oxygen evolution rate was 48 mM, 4.5 mM and 4 mM for the wild type, R233Q and R251S, respectively. Measurements of oxygen evolution in single turnover flashes confirm that the mutants are more sensitive to formate than the wild type. Measurements of chlorophyll a fluorescence decay kinetics after the second saturating actinic flash indicated that, after formate treatment, the halftime of QA- oxidation was decreased by approximately a factor of 2, 4 and 6 in the wild type, R251S and R233Q, respectively. The recombination rate between QA- and S2 was approx. 2-fold slower in R251S and R233Q than in the wild type. In the presence of 100 mM sodium formate, reactivation of the Hill reaction by bicarbonate showed that the wild type had an apparent Km for bicarbonate of 0.5 mM, while the Km values for R233Q and R251S were 1.4 and 1.5 mM, respectively. We suggest that Arg-233 and Arg-251 in the D2 polypeptide contribute to stabilization of HCO3- binding in Photosystem II. PMID- 1909179 TI - Burkitt lymphoma cell lines are prone to recombination in the switch region of the Ig mu heavy chain locus. AB - Different recombinations have been found at the Ig heavy chain gene loci in a number of sublines of the Burkitt lymphoma (BL) cell line Namalwa, following prolonged in vitro culture. The Namalwa sublines examined are DNA fingerprint identical and derived from a monoclonal source. Recombinant DNA clones were used to map the Ig heavy chain gene mutations to a region between the VDJ and C mu segment of the locus. This region is associated with Ig heavy chain class switching in normal B cells. Of 24 clones established from one subline, three were found to have additional VDJ-C mu region mutations, indicating a high frequency of mutation at this locus. PMID- 1909180 TI - Spectrophotometrical and immunochemical studies on the conformational changes in poly(dG-dC).poly(dG-dC) after modification by 4-hydroxyaminoquinoline 1-oxide. AB - Poly(dG-dC).poly(dG-dC) was modified by the reaction with 4-hydroxyaminoquinoline 1-oxide (4HAQO) in the presence of seryl-AMP. The conformations of 4HAQO-modified poly(dG-dC).poly(dG-dC) and of poly(dG-dC).poly(dG-dC) were studied by circular dichroism spectra under various salt concentration conditions. 4HAQO residues to guanine bases are inefficient in inducing the transition of poly(dG-dC).poly(dG dC) from B-form to Z-form conformation. We have elicited monoclonal antibodies against 4HAQO-poly(dG-dC).poly(dG-dC). They were characterized using enzyme linked immunosorbent assay (ELISA), radioimmunoassay (RIA) and binding to supercoiled DNA. These antibodies reacted with 4HAQO-poly(dG-dC).poly(dG-dC) specifically but not with 4HAQO-modified DNA or poly(dG).poly(dC). However, they cross-reacted with N-acetoxy-2-acetylaminofluorene-modified poly(dG-dC).poly(dG dC) in Z-form conformation. These monoclonal antibodies may recognize a unique conformation in poly(dG-dC).poly(dG-dC) after 4HAQO modification. PMID- 1909181 TI - Expression of LDL receptor, apolipoprotein B, apolipoprotein A-I and apolipoprotein A-IV mRNA in various mouse organs as determined by a novel RNA excess solution hybridization assay. AB - We report expression of LDL receptor, apolipoprotein B (apoB), apolipoprotein A-I (apoA-I) and apolipoprotein A-IV (apoAIV) mRNA in various mouse organs. These mRNA were quantified by an RNA-excess solution hybridization assay. For preparing specific probes, we cloned cDNA fragments of rat LDL receptor, apoB and apoA-I and mouse apoA-IV into the polylinker region of pGEM3Zf(+) and used the recombinant vectors for preparing 32P-labeled cRNA probes as well as RNA standards using the T7 and SP6 promoters flanking the polylinker regions. Preparation of cRNA probes and RNA standards is faster and more convenient than preparing cDNA probes and ssDNA standards. Absolute levels of mRNA were quantified in the liver, intestine, kidney, heart, lung, spleen and adrenals of females of two mouse strains. C3H/HeJ and C57BL/6J. ApoB, apoA-I and apoA-IV genes in mice are expressed in the liver and intestine and LDL receptor gene is expressed mainly in liver, intestine and adrenals. ApoA-I mRNA levels were found to be 730 and 1039 molecules per cell in liver and intestine, respectively, in C3H mice and 762 and 952 molecules per cell in C57BL mice. ApoB mRNA levels were 66 and 170 molecules per cell in the liver and intestine of C3H and 83 and 243 molecules per cell in C57BL, respectively. ApoA-IV mRNA was found to be 3525 and 2964 molecules per cell in the liver and intestine of female C57BL mice, respectively. LDL receptor mRNA levels were 39, 32 and 14 molecules per cell in the liver, intestine and adrenals of C3H. PMID- 1909182 TI - Biosynthesis of platelet activating factor and 1-O-acyl analogues by endothelial cells. AB - Mass spectrometric procedures have been used to measure 1-O-alkyl-2-O-acetyl glycero-3-phosphocholine (PAF) and a structural analogue, 1-O-acyl-2-O-acetyl glycero-3-phosphocholine, biosynthesis in stimulated human umbilical vein endothelial cells (HUVEC). The primary species of acetylated glycerophosphocholine detected were of the 1-O-acyl type, rather than PAF. The amounts of PAF synthesized were much less than reported in earlier studies. In addition, mass spectrometric procedures were used to profile the molecular species of glycerophosphocholine in HUVEC and to determine those species which have arachidonate in the sn-2 position. The pattern of the occurrence of arachidonate in the sn-2 position is very similar to the pattern of synthesis of the acetylated glycerophosphocholines. These results suggest that 1-O-acyl-2-O acetyl-glycero-3-phosphocholines may have significant but unappreciated biological activities. These results also support the view that glycerophosphocholine molecular species which have arachidonate esterified at the sn-2 position are the immediate precursors for the hydrolysis-acetylation steps which result in the synthesis of sn-2 acetylated glycerophosphocholines, including PAF. PMID- 1909184 TI - Identification of a RecA-like protein in Lactococcus lactis. AB - We have identified in Lactococcus lactis, an analogue of Escherichia coli RecA protein. Physiological responses such as ultraviolet (UV) and chemical mutagenesis and induction of prophage have been characterized and suggest the existence of RecA-like functions in this commercially important species. The putative RecA protein was detected at the position of an apparent molecular weight of 39 kDa by Western blot analysis by using antiserum against E coli RecA protein. In addition, the protein level is significantly increased after UV irradiation in a wild-type strain compared to the recombination deficient mutant strain. PMID- 1909185 TI - The recE(A)+ gene of B subtilis and its gene product: further characterization of this universal protein. AB - Although the SOS system of E coli and the SOB system of B subtilis share many similarities, there are distinct differences with respect to the regulation and specificity of the phenomena that constitute these global regulons. One of these differences resides in the regulation of the respective RecA and RecA-like proteins. In B subtilis the RecA-like protein, the RecE protein, shares 60% amino acid homology with its E coli counterpart. The E coli recA gene can complement most, but not all, of the functions that are lost in strains of B subtilis that do not produce a functional RecE protein. The DNA sequence of the recE+ gene as well as the sequence of the recE4 allele and the recA73 allele of B subtilis has demonstrated that mutants of the recE and recA loci of this bacterium actually represent alleles of the same complex gene. Accordingly, the major recombination protein of B subtilis should be referred to as RecA and the gene that encodes this protein as recA+. PMID- 1909183 TI - Overexpression of the alpha-type protein kinase (PK) C in LLC-PK1 cells does not lead to a proportional increase in the induction of two 12-O-tetradecanoylphorbol 13-acetate-inducible genes. AB - Phorbol esters, by activating protein kinase C (PKC), induce the expression of the urokinase-type plasminogen activator (uPA) gene and the proto-oncogene c-fos in LLC-PK1 (PK1) porcine kidney epithelial cells. To investigate the role of PKC in the regulation of these two 12-O-tetradecanoylphorbol-13-acetate (TPA) inducible genes, the alpha-type PKC, the predominant subtype present in the PK1 cells, was overexpressed in this cell line. Two clonal PK1 derivatives overexpressing the alpha PKC 15- and 20-fold, respectively, were established. Compared with the parental and control cells, only a modest but substantially sustained (2- to 3-fold) increase in the accumulation of uPA as well as c-fos mRNAs were observed by TPA in these cells. These results indicate that the extent of induction of these genes mediated by TPA was not proportional to the amounts of alpha-type PKC stably overexpressed in these cells, suggesting that factor(s) downstream of the activation of the alpha PKC appear to be rate limiting for the induction of both TPA-inducible genes in PK1 cells. PMID- 1909186 TI - Characterization of recF suppressors in Bacillus subtilis. AB - A recF mutation renders Bacillus subtilis cells very sensitive to DNA-damaging agents. Such a recF defect is partially suppressed either by the presence of the recA73 mutation or by the presence of a plasmid-borne, heterologous, single stranded DNA-binding (ssb) protein gene. Plasmids carrying ssb genes also suppressed the recR and recL defects. Our results suggest that suppression occurs by increasing recombinational repair. The effect of the suppressors may be at the level of induction of the SOS response. PMID- 1909187 TI - Isolation and characterisation of nuv11, a mutation affecting meiotic and mitotic recombination in Aspergillus nidulans. AB - A mutant of Aspergillus nidulans, designated nuv11, has been isolated as hypersensitive to the monofunctional alkylating agent MNNG and the quasi-UV mimetic mutagen 4-NQO. The mutation was recessive, resulting from mutation of a single gene which mapped to chromosome IV, and was non-allelic to the previously characterised repair-deficient mutations uvsB and uvsH which are also located on this linkage group. The nuv11 mutation results in slow growth, deficient intragenic and intergenic meiotic recombination, increased spontaneous chromosome instability, and increased intragenic and intergenic mitotic recombination in homozygous diploids. By screening a wild-type gene bank of A nidulans, a clone (pNUV11A40) has been isolated which complements the nuv11 mutation, restoring wild-type responses to both MNNG and 4-NQO. PMID- 1909188 TI - Effects of recombinant human interleukin-2 and excipient infusion on plasma levels of prostaglandins and thromboxane B2 in sheep. AB - Systemic administration of recombinant human interleukin-2 (rIL-2) is used for treating some patients with advanced cancer. This therapy is limited by severe adverse reactions of cardiovascular and gastrointestinal origin. The effects of rIL-2 treatment on plasma levels of some prostanoids were examined in sheep in order to elucidate the mechanism of these adverse reactions. A total of 8 adult female Suffolk sheep were used. rIL-2 (0.1 mg/kg) was infused over a 30-min period in 4 sheep. Four different sheep in the control group received an excipient, which consisted of 5% mannitol and sodium dodecyl sulfate (SDS) (187 micrograms SDS/mg rIL-2), in the same way. Plasma levels of prostaglandin (PG) F2 alpha in rIL-2-treated animals showed significant increases from 1.5 to 6 h over the excipient treated animals with a maximal increase of 138% of the pooled zero time control value (p less than or equal to 0.01) at 6 h. The pooled zero time control plasma PGF2 alpha concentration was 443.0 +/- 45.9 pg/ml. Plasma levels of 6-keto-PGF1 alpha in rIL-2-treated animals showed a significant increase (p less than or equal to 0.02) over the excipient treated animals at 0.5 h but the value was only 103% of the pooled zero time control. Plasma levels of 6-keto-PGF1 alpha in excipient-treated animals showed a maximal increase of 156% of the pooled zero time control value (55.6 +/- 8.9 pg/ml) at 5 h and it was significantly higher than the rIL-2-treated sheep.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1909189 TI - Characterization of human interferon-gamma and human interleukin-2 from recombinant mammalian cell lines and peripheral blood lymphocytes. AB - Human interleukin-2 (IL-2) and human interferon-gamma (IF-gamma) isolated from transfected heterologous cell lines were structurally compared with their natural counterparts isolated from peripheral blood lymphocytes (PBL). Several forms of IL-2 and IFN-gamma that were primarily due to differential glycosylation were produced by all cell types studied. Comparable molecular weights and sugar compositions were found for variants of natural and mammalian-derived recombinant IL-2, and variants of natural and mammalian-derived recombinant IFN-gamma. Furthermore, the specific biological activities of the natural and mammalian derived recombinant lymphokines were similar and comparable to the specific activity of the Escherichia coli-derived recombinant proteins. PMID- 1909191 TI - Particle concentration fluorescence immunoassay for measuring interleukin-6 receptor numbers. AB - Analysis of the number of receptors per cell and the affinity of the ligand/receptor interaction has provided considerable insight into the functioning of numerous cytokines. Interleukin-6 (IL-6) is a multifunctional cytokine which may have considerable clinical relevance in inflammatory or immunodeficiency diseases. Using particle concentration fluorescence immunoassay (PCFIA) technology, an assay is described which calculates the receptor number and affinity on small numbers of human cells. Resting B cells are shown to lack IL-6 receptors but activation of B cells induces up to 1,300 receptors per cell, with Kd of 1 x 10(-11) to 2 x 10(-11) M. Other recombinant mediators do not alter the binding of labeled IL-6 to the cells. PCFIA avoids the use of radioactivity and requires very small numbers of cells (2 x 10(4) per well). Potential application to the study of regulatory mechanisms and to clinical situations where small samples of blood are available is feasible. PMID- 1909190 TI - Fourier transform infrared spectroscopic study of Ca2+ and membrane-induced secondary structural changes in bovine prothrombin and prothrombin fragment 1. AB - Fourier transform infrared (FTIR) spectroscopy was used to monitor secondary structural changes associated with binding of bovine prothrombin and prothrombin fragment 1 to acidic lipid membranes. Prothrombin and prothrombin fragment 1 were examined under four different conditions: in the presence of (a) Na2EDTA, (b) 5 mM CaCl2, and in the presence of CaCl2 plus membranes containing 1-palmitoyl-2 oleoyl-3-sn-phosphatidylcholine (POPC) in combination with either (c) bovine brain phosphatidyl-serine (bovPS) or (d) 1,2-dioleoyl-phosphatidylglycerol (DOPG). The widely reported Ca(2+)-induced conformational change in bovine prothrombin fragment 1 was properly detected by our procedures, although Ca(2+) induced changes in whole prothrombin spectra were too small to be reliably interpreted. Binding of prothrombin in the presence of Ca2+ to procoagulant POPC/bovPS small unilamellar vesicles produced an increase in ordered secondary structures (2% and 3% increases in alpha-helix and beta-sheet, respectively) and a decrease of random structure (5%) as revealed by spectral analysis on both the original and Fourier-self-deconvolved data and by difference spectroscopy with the undeconvolved spectra. Binding to POPC/DOPG membranes, which are less active as procoagulant membranes, produced no detectable changes in secondary structure. In addition, no change in prothrombin fragment 1 secondary structure was detectable upon binding to either POPC/bovPS or POPC/DOPG membranes. This indicates that a membrane-induced conformational change occurs in prothrombin in the nonmembrane-binding portion of the molecule, part of which is activated to form thrombin, rather than in the membrane-binding fragment 1 region. The possible significance of this conformational change is discussed in terms of differences between the procoagulant activities of different acidic lipid membranes. PMID- 1909192 TI - Elevated levels of circulating tumor necrosis factor-alpha, interferon-gamma, and interleukin-2 in systemic reactions induced by anti-CD4 therapy in patients with rheumatoid arthritis. PMID- 1909193 TI - Faecal clearance of alpha 1-antitrypsin reflects disease activity and correlates with rapid turnover proteins in chronic inflammatory bowel disease. AB - Faecal clearance of alpha 1-antitrypsin was measured in patients with ulcerative colitis and Crohn's disease and compared with disease activity and markers of protein-calorie malnutrition. Patients with active ulcerative colitis and Crohn's disease showed elevated clearance of alpha 1-antitrypsin and clearance declined in most patients with induction of remission. However, even with inactive disease, elevated protein loss persisted in some patients, presumably reflecting residual inflammation in the intestinal mucosa. There was a significant correlation between clearance of alpha 1-antitrypsin and serum levels of retinol binding protein and transferrin in patients with ulcerative colitis and with retinol-binding protein in patients with Crohn's disease. Clearance of alpha 1 antitrypsin reflects disease activity in inflammatory bowel disease and correlates with serum levels of rapid-turnover proteins such as retinol-binding protein and transferrin, which are markers for the presence of protein-calorie malnutrition. PMID- 1909194 TI - Modulation of erythropoiesis by novel human bone marrow cytochrome P450-dependent metabolites of arachidonic acid. AB - In the hematopoietic system the adherent stromal cells produce cytokines necessary for proliferation and differentiation of hematopoietic cells. In the present study, we showed the ability of adherent stromal cells to generate novel metabolites of arachidonic acid via the NADPH-cytochrome P450-dependent monooxygenase system. These metabolites were recovered in the incubation media, suggesting their release from cells. The formation of arachidonic acid metabolites was inhibited by 7-ethoxyresorufin and SKF-525A, but not by indomethacin or BW-755C. By using two-step high-pressure liquid chromatography (HPLC), bone marrow-adherent stromal cells and incubation media showed the presence of metabolites in a peak eluted at 19 to 20 minutes. The isolated HPLC peak was used to measure its effect on colony-forming unit-erythroid (CFU-E) growth and compare it with that of synthetic cytochrome P450 arachidonate metabolites, 19- and 20-hydroxyeicosatetraenoic (HETE) acid. These bone marrow cytochrome P450 arachidonic acid metabolites at picomolar concentration potentiated erythropoietin (Epo)-induced CFU-E growth by fourfold to sixfold. Addition of 19- and 20-HETE to the bone marrow culture resulted in a potentiating effect on CFU-E number in a dose-dependent manner. 20-HETE was much more potent in stimulating CFU-E growth than 19-HETE at a similar concentration of 10(-11) mol/L. The potentiating effect of 20-HETE resulted in a shifting to the left of the dose-response curve to Epo. To substantiate the finding of an active NADPH dependent cytochrome P450-metabolizing system, we further examined the ability of adherent cells to metabolize exogenous pharmacologic compounds such as benzo(a)pyrene, a substrate for the heme-cytochrome P450 system, aryl hydrocarbon hydroxylase. The adherent stromal cytochrome P450 metabolizes benzo(a)pyrene at comparable levels to blood vessel endothelial cells. These novel observations underscore the importance of adherent stromal cytochrome P450 to metabolize endogenous substrates, including arachidonic acid, to compounds that may interact in a paracrine manner with Epodependent hematopoietic cells. PMID- 1909195 TI - Immunodepletion of extrinsic pathway inhibitor sensitizes rabbits to endotoxin induced intravascular coagulation and the generalized Shwartzman reaction. AB - We have reported earlier that immunodepletion of extrinsic pathway inhibitor (EPI) sensitizes rabbits to disseminated intravascular coagulation (DIC) induced by infusing a low concentration of tissue factor (TF). We now describe the effect of immunodepletion of EPI in rabbits administered endotoxin. Cortisone-treated rabbits were administered anti-rabbit EPI immunoglobulin (IgG) or Fab fragments or were administered control nonimmune material before an injection of endotoxin. In four of seven rabbits administered anti-EPI, plasma EPI activity levels were reduced by 70% to 80% of initial levels for 6 to 8 hours. In these rabbits the endotoxin induced extensive DIC, as evidenced by substantial decreases in fibrinogen, factor V, factor VIII, and platelets, and gross hemorrhagic necrosis of the kidneys due to massive deposition of fibrin in the glomerular microcirculation (the generalized Shwartzman reaction). In three rabbits administered anti-EPI, plasma EPI levels were only transiently reduced. In these rabbits and in four rabbits administered nonimmune IgG or Fab, endotoxin induced minimal to moderate intravascular clotting and deposits of fibrin were not found in the glomerular capillaries. Because it is believed that TF expressed on monocytes triggers endotoxin-induced coagulation, these data are taken as evidence that EPI functions as a natural anticoagulant that can regulate factor VIIa/TF activity expressed on cell surfaces in vivo. They support a hypothesis that EPI prevents thrombotic complications that might otherwise result from exposure of blood to cytokine-induced generation of small amounts of TF on cell surfaces in many inflammatory and infectious disease states. PMID- 1909196 TI - Ig VH gene expression among human follicular lymphomas. AB - Thirty-six randomly selected cases of low grade follicular lymphoma (FL) were analyzed for Ig heavy chain variable region (VH) gene expression. Assignment to one of the six human VH gene families (VH1 to VH6) was made with a polymerase chain reaction-based technique using family-specific leader primers. The frequency of VH family use in FL was found to be similar to that reported for normal peripheral blood lymphocytes and is therefore also roughly proportional to VH family size. To evaluate expression within an individual family, all of the lymphoma VH genes from the middle size VH4 family were sequenced and compared with previously published sequences. Of these eight lymphoma VH sequences, six were most closely related to just two of the 10 known functional VH4 germline genes. Nonrandom usage by FL of the JH3, JH4, and JH5 joining segments was also observed. Nucleotide sequences were also determined for 10 randomly selected lymphoma VH genes from the large VH3 family. With one possible exception, none of these lymphoma VH sequences appear to represent any of the VH3 genes that may be preferentially used in the fetal repertoire. PMID- 1909197 TI - Developing a quality assurance program for online services. AB - A quality assurance (QA) program provides not only a mechanism for establishing training and competency standards, but also a method for continuously monitoring current service practices to correct shortcomings. The typical QA cycle includes these basic steps: select subject for review, establish measurable standards, evaluate existing services using the standards, identify problems, implement solutions, and reevaluate services. The Claude Moore Health Sciences Library (CMHSL) developed a quality assurance program for online services designed to evaluate services against specific criteria identified by research studies as being important to customer satisfaction. These criteria include reliability, responsiveness, approachability, communication, and physical factors. The application of these criteria to the library's existing online services in the quality review process is discussed with specific examples of the problems identified in each service area, as well as the solutions implemented to correct deficiencies. The application of the QA cycle to an online services program serves as a model of possible interventions. The use of QA principles to enhance online service quality can be extended to other library service areas. PMID- 1909198 TI - Selective impairment of hindquarters vasodilator responses to bradykinin in conscious Wistar rats with streptozotocin-induced diabetes mellitus. AB - 1. Male, Wistar rats were treated with streptozotocin (STZ, 70 mg kg-1, i.p.) or saline and chronically instrumented with pulsed Doppler probes and intravascular catheters (implanted under sodium methohexitone anaesthesia) to allow assessment of haemodynamics in the conscious state 28 days later. 2. Control and STZ-treated rats received bolus doses of glyceryl trinitrate (10-80 nmol kg-1), acetylcholine (0.1-5 nmol kg-1) and bradykinin (0.3-30 nmol kg-1). 3. Although, as reported previously, STZ-treated rats had normal mean arterial blood pressure together with renal and mesenteric vasodilatations and hindquarters vasoconstriction relative to control rats, both groups showed similar hypotensive and regional haemodynamic responses to glyceryl trinitrate and acetylcholine. However, while the depressor effects of bradykinin were similar in control and STZ-treated rats, the former showed a hindquarters vasodilator response to bradykinin that was absent in the STZ-treated rats. 4. A loss of bradykinin-mediated vasodilatation in the hindquarters vascular bed in STZ-treated rats in the presence of normal, hindquarters vasodilator responses to other agents and normal bradykinin-mediated vasodilator responses in other vascular beds is consistent with existing evidence that the vasodilatation elicited by bradykinin in the hindquarters vascular bed is particularly dependent on nitric oxide synthesis and that this is impaired selectively in STZ-treated rats. PMID- 1909199 TI - N-nitro L-arginine causes coronary vasoconstriction and inhibits endothelium dependent vasodilatation in anaesthetized greyhounds. AB - 1. The effect of N-nitro-L-arginine (L-NNA), an inhibitor of nitric oxide biosynthesis, on large coronary artery diameter and coronary blood flow was examined in anaesthetized greyhounds. The effects of L-NNA on the coronary vascular responses to acetylcholine (ACh), glyceryl trinitrate (GTN) and 5 hydroxytryptamine (5-HT) were also assessed. 2. L-NNA (5 mg kg-1), infused into the left circumflex coronary artery, increased systemic mean arterial pressure and decreased the external diameter of the artery. Infusion of L-NNA decreased coronary blood flow in 5 of the 7 dogs tested and increased mean coronary resistance but neither of these effects was statistically significant. There was no change in heart rate. 3. Intra-arterial injection of both ACh (0.01-0.05 micrograms kg-1) and GTN (0.1-0.5 micrograms kg-1) increased large coronary artery diameter and coronary blood flow. Coronary vascular responses to the endothelium-dependent vasodilator ACh were significantly reduced by L-NNA, whereas the responses to the endothelium-independent vasodilator GTN were not significantly affected. 4. 5-HT (0.1 microgram kg-1, injected into the left circumflex coronary artery) decreased coronary artery diameter but increased coronary blood flow. After the administration of L-NNA the 5-HT-induced dilatation of the coronary resistance vessels was significantly attenuated whereas the constriction of the circumflex coronary artery was increased in 3 out of 3 dogs in which diameter could be measured, although the latter effect was not statistically significant. 5. These data indicate that L-NNA causes coronary and systemic vasoconstriction and selectively inhibits endothelium-dependent vasodilatation in the coronary circulation of the anaesthetized greyhound. Therefore endothelium-derived NO has an important role in the regulation of coronary vascular tone in the large arteries and the resistance vessels. PMID- 1909200 TI - Electrophysiological effects of the combination of mexiletine and flecainide in guinea-pig ventricular fibres. AB - 1. The effects of flecainide alone, mexiletine alone and their combination at the Na+ channel level were studied in guinea-pig papillary muscles. The maximum upstroke velocity (Vmax) was used as an indirect index of the magnitude of the fast inward Na+ current (INa). 2. In muscles driven at 0.02 Hz, neither mexiletine (10(-5) M) nor flecainide (10(-6) M) nor the combination of both drugs modified the action potential characteristics. Mexiletine, but not flecainide, increased the effective refractory period/action potential duration ratio; this enhancement was greater when flecainide was also present. 3. Mexiletine or flecainide alone produced a frequency-dependent Vmax block. Although at 0.5 Hz the blockade induced by the combination of flecainide and mexiletine was similar to that produced by flecainide alone, in muscles driven at 1 and 2 Hz the combination increased the magnitude and the onset rate of the Vmax block. 4. The time constant of recovery of Vmax block was similar in the presence of flecainide or the combination mexiletine plus flecainide (tau re = 16.4 +/- 2.3 s and 16.7 +/- 2.7 s, respectively), but the combination decreased the magnitude of the slow component of reactivation induced by flecainide (93.8 +/- 1.5% versus 68.9 +/- 1.7%). Moreover, the combination of both drugs was more effective in inhibiting the Vmax of early test stimuli than either drug alone. 5. It is concluded that the combination of mexiletine and flecainide is synergistic at driving rates faster than 0.5 Hz without detracting from the characteristics of flecainide. PMID- 1909202 TI - Early and late contraction induced by ouabain in human umbilical arteries. AB - 1. Ouabain (3 x 10(-7)-10(-4) M) evoked a biphasic contraction in human umbilical artery that consisted of an early and a late contraction. The Ca(2+)-antagonists, verapamil (10(-7)-10(-5)) M), diltiazem (10(-7)-(10(-5)) M) and nifedipine (10( 9)-10(-7)) M) inhibited the early but not the late contraction. Caffeine (5 mM) changed neither the magnitude of the peak of the biphasic contraction nor the time needed to reach it. 2. Sodium concentration reduction (140 to 0 mM, replaced by N-methyl-D-glucamine, NMG) produced dose-dependent contraction of the arterial strip in 2.5 mM Ca2+ solution after the first treatment with verapamil (10(-5) M) and caffeine (5 mM), but not in Ca(2+)-free solution. 3. After prior treatment with verapamil and caffeine, the amplitude of the ouabain (10(-4) M)-induced late contraction varied, depending on the concentration of Ca2+ (0-2.5 mM) in the medium. 4. Amiloride (5 x 10(-5) M-5 x 10(-4) M), an inhibitor of the Na(+)-Ca2+ exchange system, produced dose-dependent inhibition of the late contraction induced by ouabain (10(-5) M) after prior treatment with verapamil and caffeine. 5. The time needed to reach the peak tension induced by monensin (5 x 10(-7) M) together with ouabain (10(-6) M) was less than that with ouabain alone, but the magnitude of the peak tension was not changed. 6. These results suggest that the early and late contractions caused by ouabain respectively produce a Ca2+ influx through voltage-sensitive Ca2+ channels and Ca2+ entry through sodium-calcium (Na(+)-Ca2+) exchange. PMID- 1909201 TI - Response of the rat myometrium to phenylephrine in early pregnancy and the effects of 6-hydroxydopamine. AB - 1. The contractile responses of the longitudinal and circular muscle layers of the rat uterus to the alpha 1-adrenoceptor agonist phenylephrine were measured on days 3-6 of gestation. There was a progressive increase in sensitivity to phenylephrine in both muscle layers between days 3 and 6 of gestation. Overall, this amounted to a 13 and 9 fold increase in sensitivity in longitudinal and circular muscles, respectively. In longitudinal muscle the slope of the Hill plot was 2 on day 3 of pregnancy and was decreased to 1 thereafter. 2. The sympathetic nerve terminals innervating the smooth muscle of the uterus were destroyed by administration of 6-hydroxydopamine (2 x 50 mg kg-1) 4-7 days before testing with phenylephrine. Following this treatment there was a significant increase in sensitivity to phenylephrine on day 3 in both muscle layers. After day 4, the longitudinal muscle was less sensitive to phenylephrine. 3. In the longitudinal muscle there was a progressive increase in the contractile response to maximal concentrations of phenylephrine and to high potassium (100 mM) between days 3 and 6 of pregnancy. In the circular muscle the responsiveness to both phenylephrine and potassium remained unchanged between days 3 and 6 of gestation. 6 Hydroxydopamine had no effect on the maximal responses to phenylephrine or high potassium in either muscle layer. 4. In conclusion, denervation supersensitivity of uterine smooth muscle following injection of 6-hydroxydopamine is observed only on day 3 of pregnancy and appears to be replaced by subsensitivity by day 6. The decrease in the slope of the Hill plot in longitudinal muscle after day 3 may be explained by changes in events between activation of alpha 1-adrenoceptors and contraction. PMID- 1909203 TI - Identification and characterization of histamine H1- and H2-receptors in guinea pig left atrial membranes by [3H]-mepyramine and [3H]-tiotidine binding. AB - 1. Histamine receptors in the membranes prepared from guinea-pig left atria were characterized with [3H]-mepyramine and [3H]-tiotidine binding. 2. The binding of the H1-antagonist, [3H]-mepyramine, was saturable and of high affinity with a maximum binding capacity of 307 +/- 27 fmol mg-1 protein (n = 14) and with an equilibrium dissociation constant (KD) of 1.5 +/- 0.2 nM (n = 14). The binding was rapid and readily reversible. 3. The competition curve for [3H]-mepyramine binding by histamine was biphasic and revealed high and low affinity states of binding. The addition of 5'-guanylylimidodiphosphate (GppNHp) (100 microM) converted this heterogeneous binding into homogeneous binding of low affinity. 4. The competition curves of H1-antagonists with [3H]-mepyramine had Hill coefficients not significantly different from unity, consistent with competition with [3H]-mepyramine at a single site. GppNHp did not shift the competition curves. 5. Dissociation constants for H1-antagonists determined from inhibition of [3H]-mepyramine binding correlated well with the constants derived from inhibition of the positive inotropic response of guinea-pig left atria to histamine. 6. The H2-antagonist, [3H]-tiotidine, labelled an apparently homogeneous population of recognition sites with a maximum binding capacity of 41 +/- 8 fmol mg-1 protein (n = 6) and a KD of 10.8 +/- 1.2 nM (n = 6). 7. Although histamine competed for [3H]-tiotidine binding in a concentration-dependent manner, the curve was monophasic and was not shifted by GppNHp. 8. It is concluded that both H1- and H2-receptors exist in guinea-pig left atria. H1 receptors probably couple to intracellular effector(s) through a guanine nucleotide-dependent transducing mechanism. On the other hand, H2-receptors seem unlikely to be linked to guanine nucleotide regulatory proteins in guineapig left atria, which may explain the failure of histamine to cause an increase in cyclic AMP in spite of the presence of H2-receptors. PMID- 1909204 TI - Neuronal localization of cannabinoid receptors in the basal ganglia of the rat. AB - Cannabinoid receptors have recently been characterized and localized using a high affinity radiolabeled cannabinoid analog in section binding assays. In rat brain, the highest receptor densities are in the globus pallidus and substantia nigra pars reticulata. Receptors are also dense in the caudate-putamen. In order to determine the neuronal localization of these receptors, selective lesions of key striatal afferent and efferent systems were made. Striatal neurons and efferent projections were selectively destroyed by unilateral infusion of ibotenic acid into the caudate-putamen. The nigrostriatal pathway was selectively destroyed in another set of animals by infusion of 6-hydroxydopamine into the medial forebrain bundle. After 2- or 4-week survivals, slide-mounted brain sections were incubated with ligands selective for cannabinoid ([3H]CP 55,940), dopamine D1 3H]SCH-23390) and D2 ([3H]raclopride) receptors, and dopamine uptake sites ([3H]GBR-12935). Slides were exposed to 3H-sensitive film. The resulting autoradiography showed ibotenate-induced losses of cannabinoid, D1 and D2 receptors in the caudate putamen and topographic losses of cannabinoid and D1 receptors in the globus pallidus, entopeduncular nucleus, and substantia nigra pars reticulata at both survivals. Four weeks after medial forebrain bundle lesions (which resulted in amphetamine-induced rotations), there was loss of dopamine uptake sites in the striatum and substantia nigra pars compacta but no change in cannabinoid receptor binding. The data show that cannabinoid receptors in the basal ganglia are neuronally located on striatal projection neurons, including their axons and terminals. Cannabinoid receptors may be co-localized with D1 receptors on striatonigral neurons. Cannabinoid receptors are not localized on dopaminergic nigrostriatal cell bodies or terminals. PMID- 1909205 TI - Intracellular study of rat entopeduncular nucleus neurons in an in vitro slice preparation: response to subthalamic stimulation. AB - Responses of rat entopeduncular nucleus (EP) neurons after stimulation of the subthalamic nucleus (STh) and the morphology of the EP neurons were studied using brain slice preparations. EP neurons were classified into two types based on their electrophysiological properties as reported previously. Of 87 EP neurons, 72 were Type I and the rest were Type II. Synaptic responses to STh stimulation were different in these two cell types. STh stimulation evoked excitatory postsynaptic potentials (EPSPs) followed by strong inhibitory postsynaptic potentials (IPSPs) in Type I neurons and EPSPs without strong IPSPs in Type II neurons. The EPSPs were considered to be monosynaptic because no large change in the latency (1.7 +/- 0.5 ms) resulted by alteration of stimulus intensity. The EPSPs were reversibly suppressed by kynurenic acid in a dose-dependent manner. Bath application of (+)-tubocurarine (10-50 microM) had no effect on EPSPs or IPSPs. Bath application of bicuculline methiodide (50-100 microM) markedly suppressed IPSPs evoked by STh stimulation and at the same time increased the amplitude and duration of EPSPs without affecting the latency. In the presence of bicuculline methiodide, EPSPs could induce plateau potentials and slow action potentials. Some type I and Type II neurons were intracellularly labeled by biocytin. Type I neurons were located throughout the EP but Type II neurons were located mainly in the dorsal portion of the EP. Medium sized somata of both Type I and Type II neurons were spine-free and fusiform or round in shape. They had 3 4 thick primary dendrites with diameters of 2-5 micron that branched into thin secondary dendrites.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1909206 TI - Effect of intra-amygdala dopaminergic grafts on methamphetamine-induced locomotor activity, extracellular dopamine and dopamine metabolite overflow: a comparison with the effect of intra-accumbens grafts. AB - The effects of 6-hydroxydopamine lesions of the ventral tegmental area and following intra-amygdala or intra-accumbens dopaminergic (DAergic) grafts on methamphetamine (MAP)-induced locomotor activity were investigated in rats. Intra accumbens DAergic grafts from rat embryos restored the locomotor hyperactivity response to MAP 5 weeks after grafting, while intra-amygdala grafts did not restore responses by 10 weeks after grafting. Biochemical measurements of extracellular DAergic activity in the amygdala (AMY) by in vivo microdialysis after grafting showed no significant change in the basal levels of dopamine (DA) and partial restoration of metabolite levels. MAP induced an increase of DA efflux and a decrease in dihydroxyphenylacetic acid without a significant change in homovanillic acid, which is the same pattern of response seen in control animals. These biochemical changes are similar to those seen previously after intra-accumbens grafts. The results show that restoration of DAergic activity in the AMY in the presence of DAergic denervation of accumbens does not have an effect on MAP-induced locomotion. PMID- 1909207 TI - Jejunal mucosal lactase activity from birth to three weeks in conventionally raised calves fed an electrolyte solution on days 5, 6 and 7 instead of milk. AB - The purpose of this study was to evaluate the effect of withdrawal of lactose from the diet for 72 hours on lactase activity in the jejunal mucosa of conventionally raised calves. The descending portion of the duodenum of six Holstein calves less than 24 hours old was cannulated. The calves were fed milk except on days 5, 6 and 7 when they were given the same volume of an electrolyte solution. Sequential biopsy specimens of the proximal jejunal mucosa were obtained for three weeks and the lactase activity determined. Lactase activity was highest on day 1 and a trend toward decreased lactase activity from birth until three weeks was observed. Mean lactase activity was significantly (p less than 0.05) higher for days 1, and 3 compared to days 9, 13 and 17. The withdrawal of milk and replacement by an electrolyte solution during three days had no significant effect on jejunal mucosal lactase activity in neonatal calves. PMID- 1909209 TI - What does economics have to offer risk-benefit analysis? PMID- 1909208 TI - Hemostatic studies in racing standardbred horses with exercise-induced pulmonary hemorrhage. Hemostatic parameters at rest and after moderate exercise. AB - The purpose of this study was to determine whether a defect in hemostasis might be a factor in the etiology of exercise-induced pulmonary hemorrhage (EIPH). Hemostatic parameters were evaluated in 22 EIPH-positive and ten EIPH-negative racing horses while in a rested state. Nineteen EIPH-positive and ten EIPH negative horses were further evaluated just before and immediately after a 15 min exercise period on a 260 m oval track. When EIPH-positive and EIPH-negative horses were compared at rest, there was no significant difference in any of the coagulation and fibrinolytic parameters studied. There was however, a significant difference in platelet function as assessed by aggregometry. The platelets from affected horses were significantly less responsive than those from nonaffected horses when exposed in vitro to the platelet agonists adenosine diphosphate, collagen and platelet activating factor. Exercise tended to increase the packed cell volume and factor VIII/von Willebrand factor and to decrease platelet aggregation responses to low concentrations of adenosine diphosphate. These effects of exercise however were quantitatively similar in both EIPH-positive and EIPH-negative horses. Reduced platelet function may therefore be a contributing factor in the bleeding characteristic of horses with EIPH. PMID- 1909211 TI - Effect of allixin, a phytoalexin produced by garlic, on mutagenesis, DNA-binding and metabolism of aflatoxin B1. AB - Allixin, a phytoalexin isolated from garlic, was examined for its effects on aflatoxin B1(AFB1)-induced mutagenesis using Salmonella typhimurium TA100 as the bacterial tester strain and rat liver S9 fraction as the metabolic activation system. The effects of allixin on the binding of [3H]AFB1 to calf thymus DNA and on the formation of metabolites of [3H]AFB1 were also determined. Allixin showed a dose-related inhibition of Histidine+ revertants induced by AFB1. Allixin at 75 micrograms/ml inhibited [3H]AFB1 binding to calf thymus DNA and reduced formation of AFB1-DNA adducts. In addition, allixin exhibited a concentration-dependent inhibition of the formation of organosoluble metabolites and the glutathione conjugates of [3H]AFB1. The data indicate that the effect of allixin on AFB1 induced mutagenesis and binding of metabolites to DNA may be mediated through an inhibition of microsomal P-450 enzymes. Allixin may thus be useful in the chemoprevention of cancer. PMID- 1909212 TI - Pathological basis of failure of concurrent glyceryl trinitrate therapy to improve efficacy of tissue type plasminogen activator in coronary thrombosis. AB - STUDY OBJECTIVE: The aim was to examine the effect of glyceryl trinitrate, a potent coronary vasodilator, on the thrombolytic effects of tissue type plasminogen inhibitor (t-PA) in dogs with coronary thrombosis. DESIGN: The thrombus was formed by delivery of anodal direct current into the left anterior descending coronary artery. Fourteen dogs were randomly given t-PA alone (0.75 mg.kg-1 over 20 min) or t-PA with glyceryl trinitrate (125 micrograms.min-1 for 40 min). In four other dogs, glyceryl trinitrate was given after t-PA induced thrombolysis. Its effect on t-PA induced thrombolysis, in terms of reperfusion rate, time to thrombolysis, peak coronary blood flow, and reocclusion rate, was quantitated. Peripheral blood platelet counts and whole blood platelet aggregation were measured in all dogs. The thrombosed left anterior descending artery and normal circumflex coronary artery segments were examined by scanning electron microscopy at the end of the experiment. MEASUREMENTS AND MAIN RESULTS: The reperfusion rate in the t-PA plus glyceryl trinitrate (t-PA + GTN) group was 57% (4/7 dogs) and with t-PA alone, 71% (5/7 dogs). The time to thrombolysis in the t-PA + GTN group was greater than with t-PA alone, at 30(SD 10) v 18(7) min, p less than 0.02, and the duration of reperfusion much shorter, at 11(17) v 48(15) min, p less than 0.02. Peak coronary blood flow in the t-PA + GTN group following reperfusion was less compared with t-PA alone, at 36(52) v 53(18) ml.min-1, p less than 0.02. Reocclusion rates in the two groups were similar. Peripheral blood platelet counts decreased during thrombus formation in all dogs; this decrease stabilised when t-PA was given alone but not when it was given with glyceryl trinitrate [mean platelet count at the end of t-PA infusion 7.23(1.68) and 4.78(3.00) X 10(8).ml-1 respectively, p less than 0.02], suggesting continued sequestration of platelets in the intracoronary thrombus in the latter group. Whole blood platelet aggregation decreased significantly with t-PA alone, but less so with t-PA + GTN [magnitude of platelet aggregation 0.23(0.57) and 5.67(6.23) ohms, respectively, p less than 0.02], suggesting lower plasma concentrations of t-PA when given with glyceryl trinitrate. Glyceryl trinitrate given after thrombolysis induced by t-PA failed to sustain reperfusion. Scanning electron microscopy of occluded left anterior descending artery showed extensive endothelial injury and a thrombus composed of platelet--red blood cells--fibrin mesh. The reperfused left anterior descending artery showed extensive endothelial injury and residual thrombus consisting mostly of fibrin and red blood cells with some platelets. CONCLUSION: Glyceryl trinitrate given concurrently with t-PA or after t-PA induced thrombolysis does not modify the thrombolytic potential of t PA. The potentially "detrimental" effects of glyceryl trinitrate may be due to increase in hepatic blood flow and subsequent enhanced catabolism of t-PA. Lack of any significant effect of therapeutic dosage of glyceryl trinitrate on platelet--fibrin rich thrombus may explain the absence of a salutary action of this agent. Dynamic coronary vasoconstriction does not play an important role in coronary reocclusion after initial thrombolysis. PMID- 1909210 TI - Screening for HBsAg in pregnant women: a cost analysis of the universal screening policy in the province of Quebec. AB - We carried out a cost analysis of a universal prenatal screening policy for hepatitis B virus infection in pregnant women. A universal screening policy in the province of Quebec (87,000 births per year) would cost about $473,000 per year and the prevention of one chronic carrier, $8,915. The cost varied greatly according to the ethnic origin of the mother and the cost of the serologic test. Strategies to reduce the cost of the serologic test could greatly reduce the cost of this screening policy. PMID- 1909213 TI - Gamma/delta T cell receptor positive T cells in the inflammatory joint: lack of association with response to soluble antigens. AB - In patients with inflammatory synovitis, the proliferative response by lymphocytes from synovial fluid to soluble mycobacterial antigens is enhanced relative to those from peripheral blood. Earlier studies suggested that gamma/delta T cell receptor positive (TCR+) T lymphocytes may significantly contribute to the mycobacterial-specific synovial fluid response. We therefore examined the relationship of the T cell proliferative response to Mycobacterium tuberculosis antigens and the presence of gamma/delta TCR+ T cells employing several monoclonal antibodies. No consistent increase of gamma/delta TCR+ T cells was noted in inflammatory synovial fluids or tissues. Nonetheless, lymphocytes from the majority of the synovial fluids proliferated vigorously in response to water-soluble M. tuberculosis antigens. There was no relationship between the percentage of gamma/delta TCR+ T lymphocytes and the intensity of the proliferative response. In contrast, stimulation with whole mycobacterial organisms was capable of enriching the gamma/delta TCR+ cell population obtained from the peripheral blood of tuberculosis skin test positive normal controls and from some inflammatory synovial fluids. These observations do not support a role for mycobacteria reactive gamma/delta TCR+ synovial T lymphocytes in response to soluble mycobacterial antigens or in the local pathogenesis of inflammatory synovitis. PMID- 1909214 TI - Reversal of immune dysfunction in osteopetrotic rats by interferon-gamma: augmentation of macrophage Ia expression and lymphocyte interleukin-2 production and proliferation. AB - Lymphocytes from osteopetrotic (op) rats, compared to their normal (n) littermates, exhibit defective immune functions associated with their inability to resorb bone. Among these immune defects are the failure of their spleen cells to proliferate normally to mitogens and to generate IL-2. Addition of exogenous IL-2 failed to reverse the suppressed proliferation in the op spleen cells, indicating that additional defects were involved in the suppression. Phenotypic analysis of cellular constituents of op and n spleens revealed that the percentages of T cells, macrophages, and IL-2 receptor positive cells were not different. Furthermore, there was no difference in CD4 (W3/25) and CD8 (OX8) cells. However, the Ia+ (OX3) cells in the op spleen represented less than 50% of those found in the n spleen, but the op had higher levels of transferrin receptor (OX26). On the basis of the ability of interferon-gamma (IFN-gamma) to increase Ia expression, this cytokine was added to op spleen cells (10-50 U/ml) and found to increase the number of Ia+ cells to the level found in n spleen cells. Moreover, pretreatment of op spleen cells with IFN-gamma restored their ability to proliferate to mitogens and their responsiveness to IL-2. Not only did IFN gamma reverse the defective response to IL-2, but it also augmented the defective IL-2 production by op spleen cells. Taken together, these findings demonstrate that IFN-gamma can reverse many of the impaired immune functions characteristic of op spleen cells in vitro. Furthermore, these data suggest that IFN-gamma may provide an important avenue of treatment in these animals that may contribute to restoration of normal bone resorption. PMID- 1909215 TI - Hexadecylphosphocholine-mediated enhancement of T-cell responses to interleukin 2. AB - The effect of low-dose hexadecylphosphocholine (He-PC) on normal peripheral mononuclear cells (PMNC) was studied. Interferon-gamma (IFN-g) production, interleukin 2 (IL-2) receptor, and HLA-DR antigen expression were investigated, representing typical T-cell activation parameters. In PMNC cultures, He-PC dose dependently enhanced the production of IFN-g, provided IL-2 had been added exogenously. Without IL-2 He-PC was ineffective. In some cultures, at a concentration of 8 micrograms/ml He-PC stimulated the secretion of IFN-g more than 20-fold compared to untreated controls. Although He-PC by itself lacked mitogenic activity, this compound also stimulated IFN-g production in the presence of suboptimal doses of phytohemagglutinin (PHA). Immunofluorescence studies demonstrated that He-PC also increased IL-2 receptor and HLA-DR antigen expression under these experimental conditions. Taken together, these results indicate that He-PC may possess immunomodulatory activity also in vivo, acting as a costimulator for the IL-2-mediated T-cell activation process. PMID- 1909216 TI - The defective in vitro expression of interferon-gamma messenger RNA in rheumatoid arthritis is recovered by cycloheximide. AB - Circulating T lymphocytes from patients with rheumatoid arthritis (RA) were found to produce low concentrations of interferon-gamma (IFN-gamma) and express low amounts of this messenger RNA (mRNA) in response to stimulation with phytohemagglutinin (PHA). In this study, we have examined the superinduction effect of cycloheximide (CHX) on the IFN-gamma mRNA expression in PHA-stimulated T lymphocytes from nine patients with active RA compared to three healthy individuals. When CHX was added 6 hr postactivation, the expression of IFN-gamma mRNA in RA patients increased significantly at 24 and 48 hr (P less than 0.01) and reached levels similar to those observed in controls. We suggest that posttranscriptional events could play a role in the defective production of IFN gamma observed in RA. PMID- 1909217 TI - The contribution of specific cytochromes P-450 in the metabolism of 7,12 dimethylbenz[a]anthracene in rat and human liver microsomal membranes. AB - The role of specific cytochrome P-450 isoenzymes in the regio-selective metabolism of 7,12-dimethylbenz[a]anthracene (DMBA) has been studied in microsomal membranes from rat and human liver. An antibody inhibition study using membranes from phenobarbital-treated rats demonstrates that a member(s) of the CYP2C family accounts for up to 90% of the formation of the proximate carcinogen, DMBA-3,4-diol, and makes significant contributions to the formation of DMBA-5,6 diol and DMBA-8,9-diol. In these membranes the formation of DMBA-5,6-diol can be entirely accounted by the combined activity of members of the CYP2C and CYP2B families. The metabolism of DMBA has been investigated in human using microsomes from 10 individuals and the metabolites formed by these membranes were found to be mainly hydroxymethyl- and -diol products. The rates of formation of each metabolite show considerable interindividual variation and there was no correlation between these rates for any pairing of metabolites. The CYP content in these membranes of specific members of families 1, 2, 3 and 4 did correlate with the rates of formation of individual metabolites. Surprisingly there was no correlation between the content of CYP2C and formation of DMBA-3,4-diol but an antibody to rat CYP2C6 partially inhibited the formation of this metabolite. The results indicate that in human both inducible sub-families of CYPs, particularly of the PB-type, and constitutively expressed CYPs may be important in DMBA metabolism and that each metabolite may be produced by the combined activity of several CYP isoforms. PMID- 1909218 TI - Comparative effects of APSAC and rt-PA on infarct size and left ventricular function in acute myocardial infarction. A multicenter randomized study. AB - BACKGROUND: Recombinant tissue-type plasminogen activator (rt-PA or alteplase) and anisoylated plasminogen streptokinase activator complex (APSAC or anistreplase) have been demonstrated to limit infarct size significantly and to preserve left ventricular function when injected soon after acute myocardial infarction. However, as yet, the efficacy and safety of these two thrombolytic agents have not been directly compared in one trial; this was the aim of this study. METHODS AND RESULTS: One hundred eighty-three patients suffering from a first acute myocardial infarction were randomly allocated to either APSAC (30 units over 5 minutes) or single-chain rt-PA (100 mg over a 3-hour period) within 4 hours of the onset of symptoms. Global and regional left ventricular function were assessed from contrast angiography an average of 5.3 +/- 2.3 days after initial therapy. Radionuclide angiography and thallium-201 single-photon emission computerized tomography were performed before hospital discharge. Infarct size was assessed by single-photon emission computerized tomography and expressed in percentage of the total myocardial volume. Ninety patients received APSAC and 93 received rt-PA within a mean period of 172 +/- 52 minutes after the onset of symptoms. The two groups were similar in age, location of the acute myocardial infarction, Killip class, and time of randomization. The patency rate of the infarct-related artery was 72% in the APSAC group and 76% in the rt-PA group (NS). Initial and predischarge left ventricular ejection fraction as well as infarct size were similar in both therapeutic groups (0.50 +/- 0.14 versus 0.52 +/- 0.12 for initial and 0.48 +/- 0.10 versus 0.47 +/- 0.10 for predischarge ejection fraction, 11 +/- 7% versus 9 +/- 7% for infarct size, respectively, for APSAC- and rt-PA-treated patients). Bleeding complications requiring blood transfusion occurred in one APSAC patient and in two rt-PA patients. One patient in the rt-PA group died of a massive intracranial hemorrhage. At the end of the 3 week follow-up period, five APSAC patients (5.5%) and seven rt-PA patients (7.5%) had died. CONCLUSIONS: The early infusion of APSAC or rt-PA in acute myocardial infarction produced a similar patency rate, limitation of infarct size, and preservation of left ventricular systolic function with an equivalent rate of bleeding complications. PMID- 1909219 TI - Abnormal vasomotor changes early after coronary angioplasty. A quantitative arteriographic study of their time course. AB - BACKGROUND: To study the impact of percutaneous transluminal coronary angioplasty (PTCA) on coronary vasomotion, we prospectively analyzed spontaneous changes in coronary diameter and the response to the cold pressor test and intracoronary nitroglycerin in 11 patients subjected to successful single-vessel PTCA. METHODS AND RESULTS: All antianginal medications were stopped 48 hours before each study. The minimum diameter of the PTCA segment and the diameter of a distal segment in the angioplastied vessel and of a segment in a control vessel not manipulated by the balloon catheter or guide wire were measured by computerized edge detection immediately before PTCA and 5 minutes after, 4 hours after, and 8 days after PTCA. At 4 hours, PTCA and distal segments were constricted by 38 +/- 9% and 16 +/- 5%, respectively, compared with the values at 5 minutes (p less than 0.01). Before angioplasty, the cold pressor test caused vasoconstriction of PTCA and distal segments by 23 +/- 6% (p less than 0.0001) and 15 +/- 4% (p less than 0.008), respectively, but no constrictor response was elicited at 5 minutes or 4 hours after angioplasty. Eight days after PTCA, the basal coronary diameters were similar to those observed 5 minutes after PTCA and the response to the cold pressor test was similar to that observed before PTCA. All segments dilated significantly with nitroglycerin at all times, and no vasoconstriction changes were found in the control segments. CONCLUSIONS: Four hours after PTCA, transient spontaneous vasoconstriction of the PTCA and distal segments occurs, which is so intense that the cold pressor test does not cause any further constriction. These abnormalities resolve within 8 days of PTCA. PMID- 1909221 TI - Interferon-gamma inhibits arterial stenosis after injury. AB - BACKGROUND: Arterial injury initiates a proliferative response among the smooth muscle cells of the artery. This leads to the formation of a thickened intima that may reduce the diameter of the arterial lumen. Such intimal lesions often develop after vascular surgery and angioplastic procedures. Previous cell culture studies have shown that the lymphokine, interferon-gamma (gIFN), inhibits smooth muscle cell proliferation. METHODS AND RESULTS: We therefore tested whether administration of exogenous gIFN could inhibit the development of intimal lesions. Rat carotid arteries were denuded with a balloon catheter, resulting in the formation of a standardized intimal lesion. The animals were then treated with recombinant rat gIFN at 200,000 units (approximately 400,000 units or 100 micrograms/kg body wt) administered parenterally once daily for 7 days. Autoradiographic analysis of 3H-thymidine incorporation revealed that gIFN reduced the early smooth muscle replication by approximately 75%. gIFN treatment for 1 week resulted in a 50% reduction of intimal cross-section area at 2 weeks after injury when compared to control rats injected with buffer alone. The difference in lesion development persisted in rats analyzed 10 weeks after injury, suggesting that proliferative events during the first week determine the long-term development of the intima. Inhibition of lesion development was accompanied by expression of the class II histocompatibility (Ia) gene, RT1B, suggesting that both were directly related to the administration of gIFN. CONCLUSIONS: These results show that gIFN is a potent inhibitor of the formation of arterial proliferative lesions in vivo. It is possible that gIFN could be useful in preventing arterial stenosis after surgery and angioplasty in man. PMID- 1909220 TI - Thrombolytic and pharmacokinetic properties of chimeric tissue-type and urokinase type plasminogen activators. AB - BACKGROUND: Chimeric molecules comprising the A-chain of tissue-type plasminogen activator (t-PA) and the catalytic domain of urokinase-type plasminogen activator (u-PA) have intact enzymatic characteristics of u-PA, partial fibrin-binding properties of t-PA, and thrombolytic properties in animal models comparable with but not superior to those of single-chain u-PA (scu-PA). Deletion of the finger and growth factor domains (t-PA-delta FE/scu-PA-e) in such chimeras further reduces their affinity for fibrin. METHODS AND RESULTS: A detailed investigation of the thrombolytic potency and the pharmacokinetics of t-PA and u-PA chimeras was performed in quantitative animal models for thrombolysis. In hamsters with pulmonary embolism, in rabbits with jugular vein thrombosis, and in baboons with femoral vein thrombosis, the thrombolytic potency (percent lysis per milligram of compound administered per kilogram of body weight) of t-PA-delta FE/scu-PA-e was significantly higher than that of recombinant scu-PA (rscu-PA, Saruplase) as shown by a maximal rate of 720 +/- 170% versus 45 +/- 5% lysis per milligram of compound per kilogram of body weight (mean +/- SEM, p less than 0.01) in hamsters, 210 +/- 18% versus 49 +/- 3% lysis per milligram of compound per kilogram of body weight (mean +/- SEM, p less than 0.01) in rabbits, and 310 +/- 73% versus 90 +/- 0.3% lysis per milligram of compound per kilogram of body weight (p less than 0.01) in baboons. However, the specific thrombolytic activity (percent lysis per microgram per milliliter steady-state plasma antigen level) of t-PA-delta FE/scu-PA-e was not significantly different from that of rscu-PA in hamsters (210 +/- 57% versus 160 +/- 27% lysis per microgram per milliliter antigen level) and was lower than that of rscu-PA in rabbits (37 +/- 4% versus 130 +/- 5% lysis per microgram per milliliter antigen level; p less than 0.01). In dogs with a combined femoral vein blood clot and a platelet-rich femoral arterial eversion graft thrombosis, 0.25 mg/kg body wt bolus injections of t-PA delta FE/scu-PA-e produced significantly more venous clot lysis (90 +/- 5%, n = 10) than 0.25 mg/kg rscu-PA (26 +/- 3%, n = 10) (p less than 0.001) and, at the arterial side, more frequent (10 of 10 dogs versus three of 10 dogs) and more persistent (six of 10 dogs versus none of 10 dogs) recanalization (p = 0.002). After bolus injection in hamsters, rabbits, or baboons, t-PA-delta FE/scu-PA-e had a fourfold to sixfold longer initial half-life than rscu-PA and a slower plasma clearance of sixfold in hamsters, 10-fold in rabbits, and more than 10 fold in baboons. CONCLUSIONS: These results indicate that t-PA-delta FE/scu-PA-e has a markedly enhanced thrombolytic potency toward venous and arterial thrombi caused by a delayed in vivo clearance with relatively maintained specific thrombolytic activity. These properties suggest that the chimera may be clinically useful for thrombolytic therapy by bolus administration in patients with thromboembolic disease. PMID- 1909222 TI - Case report: duodenal diverticula and jaundice: ultrasound can be misleading. AB - Most duodenal diverticula are asymptomatic, but they may create diagnostic difficulties. We report a case of obstructive jaundice in which ultrasound revealed a mass in the region of the head of the pancreas produced by a diverticulum in the second part of the duodenum which was initially misdiagnosed as a carcinoma of the pancreas. PMID- 1909223 TI - Hypercarbic acidosis reduces cardiac resuscitability. AB - BACKGROUND AND METHODS: Marked increases in myocardial hypercarbia and acidosis accompany cardiac arrest and resuscitation. To investigate whether hypercarbic acidosis independent of oxygenation is of itself detrimental to cardiac resuscitation, three groups of six Sprague-Dawley rats were ventilated with gas mixtures containing concentrations of inspired CO2 (FICO2) of 0.0, 0.3, or 0.5, with oxygen fractions held constant at 0.5. After 4 mins of ventricular fibrillation, mechanical chest compressions were initiated with a pneumatic thumper; 2 mins later, transthoracic defibrillation was attempted. RESULTS: Each animal ventilated with FICO2 of 0.0 or 0.3 was successfully resuscitated. However, none of the animals ventilated with FICO2 of 0.5, in which aortic pH was less than 6.67 and aortic PCO2 was greater than 200 torr (greater than 26.7 kPa), was resuscitated (p less than .001). This finding contrasted with a second control group of seven identically treated animals which, in the absence of cardiac arrest, demonstrated no adverse effects after ventilation with an FICO2 of 0.5. CONCLUSIONS: Increases in FICO2 to levels of 0.5 under conditions of constant arterial oxygenation and controlled coronary perfusion pressure preclude successful resuscitation in this rodent model of CPR. PMID- 1909224 TI - Staple closure of the hypopharynx after diverticulectomy and total laryngectomy. AB - The use of stapling devices to close hypopharyngeal defects was first published in 1969 but the technique does not seem to have gained much popularity among head and neck surgeons. Fifty-nine hypopharyngeal defects were closed using a linear stapler between January, 1984, and April, 1989, at the Department of Otolaryngology, Head and Neck Surgery of the University Hospital of Zurich. Twenty closures were performed following resection of hypopharyngeal diverticula, 39 following wide field laryngectomy. A total of 10 salivary fistulae was observed: 2 after diverticulectomy (10%), 3 after laryngectomy in nonirradiated patients (11%), and 5 after laryngectomy in irradiated patients (45%). These fistula rates are comparable with average rates quoted in the literature. Only after laryngectomy for radiation failure was the fistula rate unusually high. No other complications were seen that could have been attributed to this type of pharyngeal closure. Closure of a hypopharyngeal defect with a stapler is easier and faster than with traditional suture methods. Provided the patient has not been previously irradiated, staple closure of the hypopharynx appears to be as reliable as closure by standard techniques and can be safely recommended. PMID- 1909225 TI - Imaging infections with antibodies. A method to localize occult infections. PMID- 1909226 TI - Cellular nutrition in support of early multiple organ failure. PMID- 1909227 TI - Cost-effective use of once-daily ceftriaxone in the treatment of moderate to severe infections: introduction to a symposium. PMID- 1909229 TI - Efficacy and cost-effectiveness of antibiotic monitoring at a Veterans Administration hospital. AB - A rigorous, continuously monitored antibiotic programme was initiated at our Veterans Administration hospital following evidence of inappropriate antibiotic usage. Seven hundred and thirty-one patients, mainly male, with an average age of 60 years were involved in the study; 378 were evaluable prior to policy implementation and 273 subsequently. The overall prevalence of deaths and average length of antibiotic therapy were less during the post-policy period. The number of antibiotic doses per patient was decreased by 24%. Drug costs were reduced by 32% post-policy, due largely to increased use of the longer-acting cephalosporins ceftriaxone and cefotetan. A 23% reduction in antibiotic acquisition costs was achieved over the 3-year period of the study, without detrimental effects on patient outcome. PMID- 1909228 TI - Outcome of a ceftriaxone/cefotaxime interchange programme in a major teaching hospital. AB - A two-stage intervention programme was performed to enable the effective substitution of ceftriaxone for cefotaxime in a teaching hospital with large numbers of transient prescribers. One hundred and sixteen patients with a variety of bacterial infections were randomized to an open, historical control comparative study to determine if ceftriaxone was an acceptable replacement for cefotaxime. For 6 months prior to the intervention, both cephalosporins were available on formulary. Following an initial informational stage, a therapeutic interchange programme was implemented to convert prescriptions for cefotaxime to ceftriaxone. Ceftriaxone and cefotaxime were equivalent in terms of microbiological and clinical efficacy and patient tolerance in 77 evaluable patients. No changes in prescriber service occurred after the changeover. Post intervention treatment courses required a ceftriaxone/cefotaxime interchange in 28% of the cases. Ceftriaxone appeared to be a suitable and cost-effective alternative to cefotaxime in this hospital. The intervention programme successfully invoked the formulary change with minimal expense and prescriber opposition. PMID- 1909230 TI - Cost-effective use of once-daily ceftriaxone: overview of a symposium. PMID- 1909231 TI - Once-daily ceftriaxone outpatient therapy in adults with infections. AB - Since 1981 our physicians' office has developed an outpatient parenteral antibiotic therapy programme which has shown advantages in patient care and provided significant cost savings. While we were able to provide any parenteral antibiotic available, the mainstay of our programme was ceftriaxone because of its broad range of activity, safety, and once-daily administration. Two hundred and ninety cases of outpatient ceftriaxone usage were recorded between January 1989 and March 1990. Ceftriaxone was found to be most useful for bone, soft tissue, and gynaecological infections. Not only was it highly clinically successful, but it was safe to use in the twice-weekly monitoring parameters we routinely perform in our office. The use of ceftriaxone alone during the 15-month period accounted for savings of over US $1.2 million compared to the cost of hospitalization during this period. PMID- 1909232 TI - [The implantation of the human ApoAI gene into aged animals]. PMID- 1909233 TI - [The effect of inhibitors of arachidonic acid metabolism on cholera toxin-induced experimental diarrhea]. PMID- 1909234 TI - Comparison of yearling, two-year-old and adult Thoroughbreds using a standardised exercise test. AB - The purpose of this study was to compare exercise measurements in yearling, two year-old and adult Thoroughbreds using a standardised treadmill incremental exercise test. Peak oxygen consumption (VO2 peak: 128.0 +/- 2.1, 140.0 +/- 2.1, 163.7 +/- 3.4; ml/kg/min +/- se, P less than 0.05), peak packed cell volume (PCV peak: 0.50 +/- 0.01, 0.58 +/- 0.01, 0.64 +/- 0.01 litres/litre +/- se, P less than 0.05) and the maximum number of steps completed in the exercise test (STEPmax: 7.7 +/- 0.1, 8.1 +/- 0.1, 8.6 +/- 0.1; steps +/- se, P less than 0.05) increased with age and degree of physical activity. Peak venous lactate concentration (LACpeak: 21.3 +/- 1.5, 19.5 +/- 1.7, 14.4 +/- 1.7; mmol/litre +/- se, P less than 0.05) and peak respiratory exchange ratio (Rpeak) were significantly higher in both groups of younger horses compared to the adult racehorses. Peak heart rate (HRpeak: 230 +/- 2, 231 +/- 3, 229 +/- 3; beats/min +/- se) did not change with age or training. The rate of change of VO2 between steps in the exercise test (VO2trans) was significantly lower in the adult racehorses at the highest exercise intensities. The slopes of the linear approximation between R (LinR bx), the natural log transformation of venous lactate concentration (LogLAC bx), and heart rate (HR bx) with velocity were significantly lower in the trained adult racehorses. The slope of venous lactate concentration normalised to per cent VO2peak (LogLAC per cent bx) was significantly lower and R breakpoint (R brkpt) normalised to per cent VO2peak was significantly higher in the trained adult racehorses. There was a more rapid decrease in venous lactate and a more rapid return to initial R values in the adult horses relative to the younger, untrained horses. No significant age or training effects were found in the remainder of the post exercise measurements. These results indicate that aerobic power and exercise capacity increased with age and training. Anaerobic power was already well developed even at a young age. PMID- 1909235 TI - Xylazine and tiletamine-zolazepam for induction of anaesthesia maintained with halothane in 19 horses. PMID- 1909236 TI - Preliminary observations on an alternative strategy for the control of horse strongyles. PMID- 1909237 TI - Amino acids in the neuronal microenvironment of focal human epileptic lesions. AB - Extracellular fluid was topically sampled with a dialysis probe during electrocorticography from the exposed cerebral cortex in 23 patients undergoing epilepsy surgery. Sampling was done in parallel from epileptiform regions and from non-epileptic areas. The former were classified according to the histopathology, into neoplastic, non-tumoral or 'special cases'. The epileptiform regions had significantly higher extracellular concentrations of alanine, glycine and phosphoethanolamine in the majority of the cases. The excised epileptic lesions were analyzed to provide the corresponding intracellular concentrations of amino acids. Several of the non-tumoral group showed high concentrations of GABA, ethanolamine and alanine. The intra- to extracellular concentration ratio for amino acids was low for phosphoethanolamine, glycine, serine and glutamine in most of the samples of epileptiform cortex, while the intracellular accumulative ability for ethanolamine apparently was stronger in epileptiform than in normal cortex. PMID- 1909238 TI - Epilepsia partialis continua studied by PET. AB - We report an [18F]fluordeoxyglucose (FDG)-PET study performed in an 11-year-old girl with a 5-month history of epilepsia partialis continua (epc). Visual inspection of PET images showed a hypermetabolic focus in the right central cortex and in the ipsilateral thalamus, which was confirmed by the absolute values of regional cerebral glucose metabolism (rCMRGlu). The thalamic hypermetabolism provides evidence for an involvement of thalamic nuclei in this ictally epileptic process. The scalp EEG revealed a theta-delta and sharp wave focus in the right Rolandic cortex at the same location as the hypermetabolic zone seen in PET. Simultaneously recorded EMG of the left tibialis anterior muscle showed regular jerks, time-locked to the sharp waves at the right central region, and myoclonic 'storms' during focal motor seizures. The results of the brain biopsy and the child's clinical course led us to a diagnosis of 'chronic encephalitis' of Rasmussen. PMID- 1909239 TI - A double-blind, placebo-controlled evaluation of the efficacy and safety of loreclezole as add-on therapy in patients with uncontrolled partial seizures. AB - Sixty-two patients with uncontrolled partial seizures participated in a 12-week, double-blind, placebo-controlled add-on-trial. Thirty-two patients received loreclezole and 30 a placebo as add-on therapy. Loreclezole was targeted at a plasma level of 1-2 mg/l. In spite of an antiepileptic therapy, usually with 2 or 3 antiepileptic drugs, these patients had at least 4 seizures a month during the baseline period. At the end of the treatment phase with loreclezole and placebo, individual responses varied widely. The median change in the daily seizure frequency was not significantly different in the 2 groups. However, when individual responses are considered, 6 patients in the verum group (19%) experienced a seizure reduction of 50% or more, compared with no patients in the placebo group. During the trial, only mild adverse events were reported in both the loreclezole and the placebo group, nor were any clinically relevant abnormalities seen in the haematological and biochemical analysis. The efficacy and safety of higher loreclezole plasma concentrations were studied in a long term follow-up trial, the results of which are presented in the following article. PMID- 1909240 TI - Long-term evaluation of the efficacy and safety of loreclezole as add-on therapy in patients with uncontrolled partial seizures: a 1-year open follow-up. AB - The effect and safety of loreclezole were evaluated during a long-term follow-up trial targeting higher plasma concentrations than those of the preceding controlled trial. The result is better than in the double-blind trial, in which loreclezole doses were administered to reach plasma concentrations of 1-2 mg/l and 6/32 patients (19%) of the verum group experienced a seizure reduction of 50% or more. None of the 30 placebo-treated patients experienced a similar decrease. At the end of the double-blind trial, 56 patients (29 from the original loreclezole and 27 from the original placebo group) elected to participate in the open follow-up trial. After 12 months' add-on treatment with loreclezole, mean plasma concentrations of 5.53 and 5.97 mg/l for the original placebo and loreclezole group were measured and the median decreases in seizure frequency were -44% and -40. At these concentrations, 22/56 patients (39%) showed a seizure reduction of at least 50%. PMID- 1909241 TI - Nimodipine in refractory epilepsy: a placebo-controlled, add-on study. AB - Twenty-two patients (8 male, 14 female) with refractory epilepsy entered a balanced, double-blind, placebo-controlled crossover trial of nimodipine as adjunctive therapy. Treatment periods of 12 weeks (nimodipine 30 mg tds, 60 mg tds, 90 mg tds each for 4 weeks and matched placebo) were followed by wash-out intervals of 4 weeks. Five patients withdrew (2 side-effects, 1 intercurrent illness, 2 non-compliance). Median values (placebo vs. nimodipine) did not vary for total (17 vs. 18), partial (14 vs. 18) and generalised tonic-clonic seizures (2 vs. 5) or seizure days (13 vs. 13). Monthly analysis also failed to uncover any benefit for nimodipine. Side-effects were reported no more frequently with nimodipine than with placebo and pulse and blood pressure did not alter significantly. Antiepileptic drug levels were not affected by nimodipine treatment but circulating nimodipine concentrations were low. In this trial, nimodipine did not fulfil the promise of its success in animal models of epilepsy. Enzyme induction by concurrent antiepileptic therapy may provide an explanation. PMID- 1909242 TI - Some contributions of electron microscopy to the study of the rickettsiae. AB - Electron microscopy has provided valuable insights into the study of rickettsiae as intracellular parasites from several important perspectives. This tool has allowed researchers to delineate the fine structural features of these organisms and to show that they truly resemble free-living bacteria. Furthermore, it has been shown that there are subtle, but distinct differences in the outer envelope structure of some members of the genus Rickettsia that may explain reported differences in tinctorial properties and in their sensitivity to certain antibiotics. With Coxiella burnetii, electron microscopy has helped significantly in the characterization of the pleomorphic nature of the organism including formation of terminal bodies that resemble endospores of gram-positive bacteria. Electron microsxopy has also helped to define the relationship of the rickettsiae to their host cells. For example, ultrastructural analysis can reveal whether organisms exist free within the cytoplasm or nucleus (members of the genus Rickettsia), or whether they are bound by a phagosomal or phagolysosomal membrane (Ehrlichia and Coxiella). Finally, although all rickettsiae eventually destroy their host cell, it has been shown through transmission electron microscopy that this destruction might be mediated by different mechanisms that are specific for different rickettsial species. PMID- 1909243 TI - Molecular biology of rickettsiae. AB - Our understanding of the biology of the rickettsiae, organisms that are the archetype of the obligate intracytoplasmic bacterial parasites, remains muddy and fragmentary. For example although we all appreciate that the rickettsiae can exploit their unique environment, the host cell cytoplasm, but are unable to grow axenically, the basis of this fact is still one of microbiology's central mysteries. It is unfortunate, but true, that because of the inherent difficulty of working within this system, progress on the answers to such questions will be slow and laborious. However, with the application of molecular biological methods, that is, the powerful modern approaches of genetics and biochemistry, the rickettsiology community has the realistic prospect that this field is far from being at a stand-still and that significant increases in our comprehension of the fundamental problems of rickettsial biology are occurring and will continue to occur at ever accelerating rates. Some examples, both in terms of scientific conclusions and technical approaches, of the progress made in recent years and expectations for the near future will be presented. PMID- 1909245 TI - Recent studies on scrub typhus and Rickettsia tsutsugamushi in Shandong Province- China. AB - In an outbreak of scrub typhus occurred 138 cases in 1986 in Menying County of Shandong Province of China which were confirmed through clinical and epidemiological surveys and laboratory techniques. In the endemic areas, the predominant species of mite is Leptotrombidium (L.) scutelarae and the predominant rodent is Apodemus agrarius, which may be the main vector and reservoir. Several strains of Rickettsia tsutsugamushi (R.T.) were obtained from mites, wild mice and patients, of which 3 human strains (SDH871, SDH875, SDH878) cause illness and some deaths in mice, except SDH871. The LD50 of SDH878 is 3.4. Cross-protection was observed among the strains, SDH871, SDH878, and prototype strain karp. Also the antibodies in mucoid peritoneal fluid were detectable with high titer. Shandong R.T. belongs to the serotype of the Gilliam strain. PMID- 1909246 TI - [The effect of nimodipine and verapamil on the blood supply and vascular reactivity of the brain]. AB - In experiments on conscious rabbits with electrodes implanted into the brain it was found by using hydrogen clearance method that nimodipine (0.1-0.06 mg/kg) and verapamil (0.3-1 mg/kg) increase the local blood flow to the decreasing degree in the cerebral hemispheric cortex, hypothalamus and thalamus. This is associated with a decrease in reactivity of the vessels of the above mentioned brain structures determined by the dilatory reaction to the dosed inhalation of carbon dioxide. PMID- 1909244 TI - A comparative view of Rickettsia tsutsugamushi and the other groups of rickettsiae. AB - Recent researches on the rickettsial group microorganisms are summarized in their comparative aspects of morphology, cultivation and multiplication, susceptibility to chemotherapeutics, chemical structure of envelopes, nucleic acid, protein constitution, and gene structures. From this overview, Rickettsia tsutsugamushi seems to have different properties from the others and should be reclassified into a new genus, and a new species name as Orientia tsutsugamushi is proposed. PMID- 1909247 TI - Glucose enhances type IV collagen production in cultured rat glomerular mesangial cells. AB - Type IV collagen production by cultured glomerular mesangial cells and the effect of glucose on it were evaluated in order to explore the possible contribution of mesangial cells to the accumulation of type IV collagen in mesangial matrix typically seen in diabetes. Type IV collagen was measured quantitatively by enzyme-linked immuno-sorbent assay. The majority of type IV collagen was secreted into culture media and secreted-type IV collagen increased with cell growth in early log phase and decreased in late log phase and after confluency. By exposing the cells to high concentrations of glucose (27.8 mmol/l), both secreted- and cell-associated-type IV collagens increased significantly compared with the cells cultured under normal glucose concentrations (5.6 mmol/l) or under equivalent concentrations of mannitol, resulting in a significant increase in total type IV collagen accumulation from 32.1 +/- 6.4 (under 5.6 mmol/l glucose) to 51.0 +/- 4.6 micrograms/dish (mean +/- SD, n = 4) on day 4, from 113.6 +/- 6.6 to 156.8 +/ 7.1 on day 6, from 248.5 +/- 15.2 to 310.0 +/- 12.6 on day 8 and from 372.4 +/- 14.8 to 507.9 +/- 17.2 on day 12. These results indicate the importance of glucose-induced alteration of mesangial cell function in the development of diabetic mesangial expansion. PMID- 1909248 TI - Alteration in the temporal organisation of insulin secretion in type 2 (non insulin-dependent) diabetic patients under continuous enteral nutrition. AB - Concomitant oscillations of plasma glucose, insulin and C-peptide levels with a period of about 80 min between peak levels have been identified in normal man. To determine whether these oscillations persist in Type 2 (non-insulin-dependent) diabetic patients, peripheral plasma levels of glucose, insulin and C-peptide were measured at 10 min intervals over 12 h in six patients and in six matched control subjects during continuous enteral nutrition (90 kcal.h-1;50% carbohydrate, 35% fat, 15% protein). The insulin secretion rate was estimated from peripheral C-peptide levels using an open two-compartment model. For the control subjects, mean plasma glucose, insulin and insulin secretion profiles rose sharply and then attained a steady-state; in contrast, for the diabetic patients, the mean insulin and insulin secretion profiles were characterized by a slow ascending trend throughout the day. Mean glucose levels rose sharply and reached higher levels than in the control subjects. The individual 12 h profiles revealed synchronous oscillations of plasma glucose, plasma insulin, and insulin secretion in the control subjects. In the diabetic patients, the number of plasma insulin and insulin secretion pulses was significantly lower; they had a smaller amplitude and were less frequently associated with the glucose pulses. However, plasma glucose levels had a similar oscillatory pattern in the diabetic patients compared with the control subjects, albeit with a higher absolute amplitude. The poor association between glucose and insulin secretion pulses in the diabetic patients suggests that insulin pulses are insufficient to account for the glucose pulses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1909249 TI - Acetylcholinesterase fiber-optic biosensor for detection of anticholinesterases. AB - An optical sensor for anticholinesterases (AntiChEs) was constructed by immobilizing fluorescein isothiocyanate (FITC)-tagged eel electric organ acetylcholinesterase (AChE) on quartz fibers and monitoring enzyme activity. The pH-dependent fluorescent signal generated by FITC-AChE, present in the evanescent zone on the fiber surface, was quenched by the protons produced during acetylcholine (ACh) hydrolysis. Analysis of the fluorescence response showed Michaelis-Menten kinetics with a Kapp value of 420 microM for ACh hydrolysis. The reversible inhibitor edrophonium (0.1 mM) inhibited AChE and consequently reduced fluorescence quenching. The biosensor response immediately recovered upon its removal. The carbamate neostigmine (0.1 mM) also inhibited the biosensor response but recovery was much slower. In the presence of ACh, the organophosphate (OP) diisopropylfluorophosphate (DFP) at 0.1 mM did not interfere with the ACh dependent fluorescent signal quenching, but preexposure of the biosensor to DFP in absence of ACh inhibited totally and irreversibly the biosensor response. However, the DFP-treated AChE biosensor recovered fully after a 10-min perfusion with pralidoxime (2-PAM). Echothiophate, a quaternary ammonium OP, inhibited the ACh-induced fluorescence quenching in the presence of ACh and the phosphorylated biosensor was reactivated with 2-PAM. These effects reflected the mechanism of action of the inhibitors with AChE and the inhibition constants obtained were comparable to those from colorimetric methods. The biosensor detected concentrations of the carbamate insecticides bendiocarb and methomyl and the OPs echothiophate and paraoxon in the nanomolar to micromolar range. Malathion, parathion, and dicrotophos were not detected even at millimolar concentrations; however, longer exposure or prior modification of these compounds (i.e., to malaoxon, paraoxon) may increase the biosensor detection limits. This AChE biosensor is fast, sensitive, reusable, and relatively easy to operate. Since the instrument is portable and can be self-contained, it shows potential adaptability to field use. PMID- 1909251 TI - Epidemic virus E hepatitis. PMID- 1909250 TI - Selective angiography for diagnosis and treatment for intestinal bleeding. AB - In case of intestinal bleeding, selective angiography is very informative to detect the cause of bleeding and the site of bleeding. Major diseases examined were ischemic lesions of intestine diverticulosis, myogenic tumors, and severe cases of ulcerative colitis. Operations were carried out when indicated. To the rest of the cases interventional angiography was carried out. Interventional angiography for intestinal bleeding was performed to 52 cases inclusive of 9 cases of bleeding from the tumor, 2 cases of diverticulosis, 3 cases of intestinal Behcet and 28 cases of severe ulcerative colitis. Administered drugs were continuous perfusion of vasopressin to the ruptured vessels and water soluble bolus intraarterial injection of prednisolone to the inflammatory process of ulcerative colitis. All the vasopressin cases were responded to this therapy. Efficacy of intraarterial injection of prednisolone was evaluated in 56 cases including the cases of cooperative study group. Efficacy was compared to the 5 days intensive intravenous therapy, revealing the similar response rate. It was also reported that seven cases to which the 5 days intensive therapy was ineffective responded to intraarterial injection therapy. Mechanism of intraarterial injection therapy was studied by analyzing the pre and post angiographical findings and by measuring mucosal blood flow and oxygen saturation. Administered high dose of prednisolone may improve the microcirculation. Further studies were indicated. PMID- 1909253 TI - A small epidemic of enterically transmitted non-A, non-B acute hepatitis. PMID- 1909252 TI - Epidemiology of hepatitis E in China. AB - A total of 9 hepatitis E epidemics have been documented in China since 1982. Five of them were waterborne and four foodborne, and they occurred in 6 of 30 provinces or autonomous regions in the country. The disease most frequently affects young adults, with fewer cases in children and the elderly. A relative male excess of cases has been observed. However, the fatality rate in female patients with hepatitis E is significantly higher than in males. The disease has a distinctive autumn seasonality in endemic areas. A peak of fecal excretion of hepatitis E virus is found at the late incubation period and early acute phase. The incubation period of the disease ranges from 15 to 75 days, with a mean of 36 days. A randomized double-blind and controlled study showed that human immune serum globulin had no prophylactic effects on hepatitis E. PMID- 1909254 TI - Hepatitis E virus (HEV): the novel agent responsible for enterically transmitted non-A, non-B hepatitis. AB - A normally endemic form of viral hepatitis is the cause of major epidemic outbreaks in developing countries. This disease has a global distribution and has been referred to as water-borne, epidemic or enterically transmitted non-A, non-B hepatitis (ET-NANBH). Although the fecal-oral route of transmission predominates, person-to-person routes of exposure were also suggested in some epidemiologic studies. The disease has been documented as having an extremely high mortality in pregnant women (approximately 20%). Sporadic cases of ET-NANBH, as well as imported travel exposures, have been reported in developed countries. Molecular cloning was hampered by the lack of a tissue culture system for virus propagation, however, an available animal model and a newly developed non specific amplification procedure were used to clone and identify an exogenous cDNA (ET1.1) from a Burma-isolate infected animal. Molecular clones were also identified by immunoscreening of a cDNA library made from a fecal specimen collected from a Mexican outbreak of ET-NANBH. The isolation and sequencing of a set of overlapping cDNA clones had led to the recognition that this form of hepatitis is caused by a virus unlike any of the other viral hepatitis agents. The molecular characterization of HEV will lead to important pathobiologic insights and hasten the development of potentially useful diagnostic and therapeutic products for ET-NANBH. PMID- 1909255 TI - Animal model, virology and gene cloning of hepatitis E. AB - We have developed animal models of viral hepatitis E using cynomolgus and rhesus monkeys. They developed acute biochemical and histological hepatitis after the inoculation of virus particles with identical kinetics and magnitude for the sixth subpassage. Virus particles multiplied in hepatocytes and were excreted into feces via bile. Additionally, a transient viremia was recognized. Molecular cloning of virus gene cDNA was successfully accomplished from two separate libraries (HT3 and NE). These clones were expressed into polypeptides having immunological epitopes, which were used for antibody assay of sera of monkeys and patients with positive results. PMID- 1909256 TI - Hepatitis C virus infection in Japan. AB - Because of the high incidence of non-A non-B post transfusion hepatitis and its relation to hepatocellular carcinoma, HCV antibody screening for blood transfusion was begun in November 1989. Seroepidemiological studies revealed the great magnitude of HCV infection in acute hepatitis, chronic hepatitis, liver cirrhosis and hepatocellular carcinoma in Japan. Approximately 1.6 million HCV antibody-positive persons are now in Japan. Major routes of infection are considered to be horizontal blood borne infection in the past and blood transfusion. PMID- 1909257 TI - Seroepidemiology of HCV and HBV infection in northern China. AB - The HCVAb positive rate in normal population in Beijing was 2.1% and HBsAg positive rate was 2.5%. There is an increasing tendency in the aged group. Plasmapheresis might have been the major cause of HCV transmission in blood donors in the Hebei area. There was a high prevalence of HCVAb and HBsAg in chronic liver diseases in the Beijing area and the HCVAb-positive rate significantly increased corresponding to disease progression. PMID- 1909258 TI - Seroprevalence of antibody against hepatitis C virus (anti-HCV) in various groups of individuals in Korea. AB - We studied the prevalence of anti-HCV in 585 sera from various individuals, using enzyme immunoassay (EIA, Abbott Lab.). Anti-HCV was detected in 16 (10.7%) out of the 150 patients with HBsAg positive liver diseases diagnosed by liver biopsy and they consisted of none out of 10 acute viral hepatitis, 3 out of 15 chronic persistent hepatitis, 4 out of 50 chronic active hepatitis, 2 out of 32 liver cirrhosis, and 7 out of 43 hepatocellular carcinoma. Anti-HCV was detected in 43 (45.3%) out of 95 patients with HBsAg negative liver diseases diagnosed by liver biopsy and they consisted of 5 out of 8 acute viral hepatitis, 2 out of 10 chronic persistent hepatitis, 17 out of 30 chronic active hepatitis, 4 out of 15 liver cirrhosis, and 15 out of 32 hepatocellular carcinoma. Anti-HCV was detected in 22 (38.6%) out of 57 hemodialysis patients, in 3 (6.7%) out of 45 kidney transplants, in 2 (11.1%) out of 18 fatty liver diagnosed by liver biopsy, in 2 (1.3%) out of 150 healthy blood donors, in none out of 40 healthy volunteers, in 6 (31.6%) out of 19 rheumatoid arthritis and in 6 (54.5%) out of 11 systemic lupus erythematosis cases. There were familial clusters of chronic liver diseases in 4.7% of patients with HBsAg negative/anti-HCV positive chronic liver diseases, while in 19.4% of patients with HBsAg positive/anti-HCV negative liver diseases. Incidence of anti-HCV within patients with HBsAg positive liver diseases was higher in HBsAg negative patients than in HBsAg positive patients (17.6% and 10.3%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1909259 TI - Hepatitis C virus infection in Taiwan. AB - To investigate the epidemiology of HCV in Taiwan, anti-HCV was studied by radioimmunoassay or enzyme immunoassay in patients with chronic liver disease, healthy adults, and subjects at risk. The anti-HCV prevalence was 0.95% in 420 volunteer blood donors, 90% in 100 hemophiliacs and 81% in 58 parenteral drug abusers. Anti-HCV was present in 6 (7.7%) of 78 HBsAg-positive and 28 (65%) of 43 HBsAg-negative patients with chronic hepatitis, 3 (10%) of 31 HBsAg-positive and 13 (43%) of 30 HBsAg-negative cirrhotics, and 7 (17%) of 42 HBsAg-positive and 15 (63%) of 24 HBsAg-negative patients with HCC. An outbreak of non-A, non-B hepatitis revealed 18% of 57 patients to be positive for anti-HCV. In a prospective study of PTH, 37 or 13% patients contracted hepatitis and 22 (60%) were due to HCV, and at least 17 (77%) of them became chronic. Cloning of HCV genome in a Taiwanese patient with acute posttransfusion non-A, non-B hepatitis by using reverse transcription polymerase chain reaction was performed, and partial characterization of the nucleotide sequences showed 80% and 92% homology as compared to HCV sequences from Chiron and one of the published Japanese isolates, respectively. It is concluded that HCV infection plays a relatively minor role in HBsAg-positive liver decrease in Taiwan, but is strongly associated with HBsAg-negative chronic liver disease and HCC. It is also important in PTH, and the infection is extremely common in hemophiliacs and parenteral drug abusers. The Taiwanese strain of HCV seems more similar to that from Japan, as revealed by nucleotide sequences. PMID- 1909260 TI - Hepatitis C virus infection in patients with chronic liver diseases in an endemic area for hepatitis B virus infection. AB - Taiwan is an endemic area for hepatitis B virus (HBV) infection, which is responsible for up to 80% of chronic liver diseases there. In contrast to an HBV carrier rate of 15-20% in the general population, only 1% of its population are seropositive for anti-HCV. To evaluate the role of HCV infection in chronic liver diseases in Taiwan, serum anti-HCV was studied using an enzyme immunoassay in 123 "healthy" administration staff of the hospital, 724 hepatitis B surface antigen (HBsAg)-positive and 157 HBsAg-negative patients with chronic liver disease. The prevalence of anti-HCV was 0.8% in the hospital staff, 24.3% in HBsAg-positive and 80.9% in HBsAg-negative patients with chronic liver diseases. Anti-HCV was positive in 10 (9.6%) of 104 HBsAg-positive and 31 (77.5%) of 40 HBsAg-negative patients with inactive chronic hepatitis; 94 (27.2%) of 346 HBsAg-positive and 53 (85.5%) of 62 HBsAg-negative patients with active chronic hepatitis; 49 (26.1%) of 181 HBsAg-positive and 33 (86.8%) of 38 HBsAg-negative patients with cirrhosis; 23 (26.7%) pf 86 HBsAg-positive and 10 (58.8%) of 17 HBsAg-negative patients with hepatocellular carcinoma. In HCV infected HBsAg-positive patients, the optical density was usually lower, and anti-HCV became negative in 27% on follow-up. HCV infection tends to occur more frequently in older, HBeAg-negative and anti-HD-positive patients with chronic HBV infection. It is concluded that HCV not only is the major agent for non-B chronic liver diseases but also plays a significant role in HBsAg-positive chronic liver diseases in Taiwan. PMID- 1909261 TI - Seroepidemiology of hepatitis C virus infection in the Philippines: a preliminary study and comparison with hepatitis B virus infection among blood donors, medical personnel, and patient groups in Davao, Philippines. AB - To determine the seroprevalence of hepatitis C virus in the Philippines and compare it with the seroprevalence of hepatitis B virus infection, HBV and HCV markers in 594 serum samples collected from 392 blood donors, 123 medical and paramedical personnel, and 80 patients (45 liver diseases: 25 acute hepatitis, 9 liver cirrhosis, and 11 hepatocellular carcinoma; 28 hepatitis B carriers, and 7 chronic renal failure patients undergoing dialysis) in Davao, Mindanao Island, Philippines, were examined. HBsAg was determined by RPHA, anti-HBc by HI, anti HBs by PHA, and HBsAg subtypes, HBeAg, and anti-HBe by EIA. HCV markers determined were anti-HCV (anti-C100-3) by ELISA (Ortho Diagnostic Systems), and anti-HCV core (anti-CP9 and/or anti-CP10) also by ELISA. Results showed that 9 (2.2%) blood donors were anti HCV positive; 69 (15.4%) were anti-HCV core positive Nine (2.2%) were HBsAg carriers; 240 (61.3%) were anti-HBs and/or anti HBc positive (HBsAg carriers excluded from this group). Two of 123 medical and paramedical staff (1.6%) were anti-HCV positive; 11 (8.1%) were anti-HCV core positive; Eight (6.5%) were HBsAg carriers and 81 (65.8%) anti-HBs and/or anti HBc positive. Five of 11 (45.4%) hepatocellular carcinoma patients were HBsAg carriers; 2 were anti-HCV core positive. Two of 9 liver cirrhosis patients were anti-HCV positive (1 to anti-HCV and the other to anti-HCV core).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1909262 TI - The prevalence of hepatitis C virus antibody in high risk group of Thai children and adults. AB - The prevalence of anti-HCV is about 1% among the blood donor population. Among 98 children with hemoglobinopathy, age ranging from 2-16 years, anti-HCV was detected in 14 (14%). The average age of the positive group was significantly higher than the negative (10.6 + 2.9 vs 8.1 + 3.9 years P less than 0.05). Numbers of transfusions were 54 + 39 in positive cases as compared to 38.5 + 36 in negative cases but this and were not statistically significant. Anti-HCV was found in 0/18, 0/3 and 0/12 in the HBsAg-positive chronic hepatitis, cirrhosis and hepatocellular carcinoma respectively, whereas it was found in 10/24 (42%), 3/13 (23%) and 0/8 in the HBsAg-negative chronic hepatitis, cirrhosis and hepatocellular carcinoma group. In an adult multiple transfused group of 153 patients who suffered from various hematologic diseases 50 (32.6%) were positive for anti-HCV. If the presence of anti-HCV indicates the presence of hepatitis C virus in the body, we expect that many of these patients will have chronic hepatitis and subsequently cirrhosis. Therefore screening of all donor blood should be adopted in all institutions concerned. PMID- 1909263 TI - The prevalence of antibody to hepatitis C virus (anti-HCV) in patients with acute and chronic liver diseases in Jakarta, Indonesia. AB - The seroepidemiology of HBV and HCV infections in the patients with acute and chronic liver diseases in Jakarta was investigated. The sera from 141 cases with acute hepatitis, 176 liver cirrhosis and 70 hepatocellular carcinoma (HCC) were examined. Anti-HA IgM, HBsAg, anti-HBc IgM and anti HCV (Ortho) were detected by Elisa method. In acute hepatitis, 83 cases (58.9%) out of 141 cases were hepatitis A and 9 cases (6.4%) hepatitis B. The others were diagnosed non-A, non B (NANB) hepatitis and anti-HCV in 4 cases (11.8%) out of 34 cases with NANB hepatitis was positive. The low prevalence of anti-HCV in acute NANB hepatitis seems to be due to inadequate date of serum sampling. HBsAg and anti-HCV in liver cirrhosis were positive 36.5% and 73.9% respectively, including 22.7% of double infection. HBsAg and anti-HCV in HCC were 58.6% and 34.2%, including 17.1% of double infection. In 16.7% fo chronic liver disease (liver cirrhosis and HCC), neither HBsAg nor anti-HCV were detected. PMID- 1909264 TI - Hepatitis B and C virus infection in Ujung Pandang, Indonesia. AB - A survey was performed to investigate HBV and HCV infection in Ujung Pandang. The total number of subjects was 406; 196 blood donors, 78 cases of acute hepatitis, 43 of chronic hepatitis, 58 of liver cirrhosis and 31 of hepatocellular carcinoma cases. HBsAg, anti-HBs and anti-HBc as HBV markers and anti-HCV (ELISA, Ortho) as an HCV marker were tested. Positive rates of HBsAg and anti HCV among blood donors were 7.1% and 3.1% respectively, and there was no significant difference among age groups. Donors negative for all viral markers accounted for 21.4%. Of acute hepatitis cases, 18 (23.1%) cases were hepatitis A and 8 (10.3%) cases were hepatitis B, one case of which was considered to be double infection. Acute exacerbation cases of HBV carriers were 16 (20.5%), of which 6 cases were positive for HCV antibody. Those diagnosed non-A, non-B hepatitis were 37 (47.4%), of which 3 cases where positive for HCV antibody. Blood samples from all of acute hepatitis cases were obtained within 1 week after onset of the disease, thus, it was not possible to accurately assess prevalence of hepatitis C. Positive rates on HBsAg among chronic hepatitis, liver cirrhosis and hepatocellular carcinoma were 25.4%, 32.8% and 35.5% respectively, while those for HCV antibody were 16.3%, 43.1% and 35.5% respectively. Positive rates of HBsAg and HCV antibody for overall chronic liver diseases were 31.1% and 32.6%, and 14 (10.6%) were positive for both markers. PMID- 1909265 TI - Hepatitis C virus (HCV) infections in New Zealand. AB - Preliminary studies of the seroprevalence of hepatitis C antibody (anti-HCV) in selected New Zealand populations, reveal similarities to other Western countries. High rates occur in haemophiliacs and intravenous drug users with relatively low rates in routine blood donors. Unlike hepatitis B virus infections anti-HCV does not appear to be more prevalent in Maoris and Pacific Islanders living in New Zealand. Chronic liver disease is associated with anti-HCV. The frequency of anti HCV in homosexuals and persons attending sexual disease clinics is higher than that found in blood donors. Further detailed studies of the frequency of anti-HCV in New Zealand populations are now required to extend the present baseline data. PMID- 1909266 TI - Hepatitis C virus infection is the major cause of severe liver disease in India. AB - The present study describes the status of hepatitis C virus infection in 167 patients with severe forms of liver diseases in India. The anti-HCV positivity rate was recorded as 43%, 47%, and 42% in patients with FHF, SAHF, and CAH respectively. HBV and HCV coinfection was recorded in 28% of FHF, 43% of SAHF and 75% of the CAH cases. Superinfection of HCV in HBsAg carriers was recorded in the 54% cases of FHF, 60% of SAHF and 42% of the CAH. None of these 167 patients was positive of HAV-IgM. Further, 27.7% of FHF, 26.4% of SAHF and 15.2% of CAH cases were neither HBV nor HCV markers positive. These can be labelled as non-A, non-B and non-C infections. PMID- 1909267 TI - Seroepidemiology of HBV and HCV infection in Jakarta, Indonesia. AB - A total of 545 serum samples were consecutively collected from patients with acute hepatitis, chronic hepatitis, liver cirrhosis, hepatocellular carcinoma, chronic hemodialysis and voluntary blood donors to study the seroepidemiology of HBV and HCV infection in Jakarta. Fourteen out of 243 or 5.8% samples from blood donors were HBsAg-positive, while HCV-antibodies (anti-C100 and/or anti-CP9 and/or anti-CP10) positivity rate was found in 59 out of 243 or 24.3%. Out of 91 donors aged 29 years or younger, 15 (16.5%) donors turned positive for HCV antibody (-ies), while out of 152 donors aged 30 years or above, 44 (28.9%) donors were anti-HCV-positive, showing a higher HCV-antibody prevalence among higher age group. Among 88 acute hepatitis patients, 33 (37.5%) cases, 10 (11.4%) cases, 15 (17.0%) cases and 30 (34.1%) cases were diagnosed as hepatitis A, hepatitis B, acute exacerbation of HCV carriers, and NANB hepatitis respectively. HCV-antibodies were found in 15 (45.5%) of hepatitis A cases and 6 (40.0%) of acute exacerbation of HBV carrier cases, but found only in 9 (30.0%) of acute NANB hepatitis cases. Positivity rates of HCV-antibodies among 23 chronic hepatitis, 80 liver cirrhosis and 64 hepatocellular carcinoma cases were 78.3%, 75.0% and 65.6% respectively, while 30.4%, 30.0% and 45.3% of the respective groups were positive for HBs antigen. Among 47 hemodialysis cases, 97.9% and 6.4% were positive for HCV antibodies and HBs antigen respectively. It was concluded that: (1) HBV infection rate is high among blood donors and patients with acute and chronic liver diseases. (2) HCV infection rate is high among blood donors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1909268 TI - Hepatitis C virus infection in patients with chronic liver diseases. AB - Antibodies against hepatitis C (HCV) in 512 patients were measured by an enzyme immunoassay (Ortho-HCV ELISA). The frequency of anti-HCV was 80%, 86%, 85% in nonB (NB) chronic hepatitis (CH), cirrhosis (LC), hepatocellular carcinoma (HCC), respectively; 70%, 90% in alcoholic (AL) LC, HCC; 15%, 33%, 58% in hepatitis B (HB) CH, LC, HCC, respectively. Anti-HCV positive cirrhotics had a shorter survival time and earlier development of HCC than anti-HCV negative cirrhotics. The findings suggest that HCV is a major cause of NB chronic liver diseases and may play a pathogenetic role in AL and HB liver diseases. PMID- 1909269 TI - The prevalence of anti-HCV antibodies in hemodialysis patients. AB - The prevalence of antibodies to hepatitis C virus (anti-HCV) was assessed in 489 hemodialysis patients and 152 members of the staff of dialysis units, using an Ortho HCV Ab ELISA Test. Of the 489 patients, 100 (20.4%) had anti-HCV, a significantly greater rate than was found in either staff members (0.7%, P less than 0.01) or local healthy blood donors (1.1%, P less than 0.001). Anti-HCV positivity was apparently related to the duration of hemodialysis. PMID- 1909270 TI - Detection of anti-hepatitis C virus antibody in fulminant hepatic failure. AB - Serial serum samples obtained from 27 patients with fulminant hepatic failure (FHF) in a variety of etiology were tested for anti-hepatitis C virus antibody (anti-HCV) with uses of two different assay systems. The incidence of anti-HCV in patients with FHF due to hepatitis B (Ortho test system; 7/11, 63.6%: Abbott test system; 9/11, 81.8%) was found to be significantly higher than that in acute HBV hepatitis (Ortho test system; 0/17, 0%) (P less than 0.001). In particular, all 3 post-transfusion HBV-FHF patients were positive for the antibody using both Ortho and Abbott test systems, and cut-off index in those patients was serially increased. On the other hand, cut-off index in anti-HCV positive patients with sporadic hepatitis A virus (HAV)- and HBV-FHF was high even prior to plasma exchange therapy, and gradually decreased. These results strongly suggest that in patients with post-transfusion HBV-FHF, HCV was superinfected over HBV and in the sporadic HAV- and HBV-FHF patients, HAV or HBV were co-infected over HCV carrier. In any events, co-infection and/or superinfection of HCV may play an important role in the development of this fatal disease. PMID- 1909271 TI - Acute post-transfusion fulminant hepatitis C virus infection: a case report. AB - A 21 year old woman developed acute fulminant hepatitis following a transfusion of hepatitis C virus (HCV) infected blood. The patient received a liver transplant and is now well and HCV antibody negative. PMID- 1909272 TI - Treatment of chronic non-A, non-B hepatitis with interferon. AB - The efficacy of interferon therapy (IFN) was investigated in 46 patients with chronic non-A, non-B (NANB) hepatitis, of would 40 (87.0%) were positive for anti HCV antibody (Ab) (C-100-3). Three kinds of IFN were used; human lymphoblastoid interferon (HLBI), interferon alpha-2b and interferon beta. Total doses of IFN ranged from 1 million units (MU) to 10 MU and treatment duration ranged from 2 weeks to 144 weeks. Of 46 patients 34 (73.9%) responded to IFN. Nine patients have maintained normal ALT levels and 5 patients have maintained near-normal ALT levels for more than 6 months after cessation of IFN treatment. In these cases the titers of anti-HCV Ab had decreased significantly at the end of IFN therapy and 6 months after IFN therapy respectively. The mean age was young and the mean disease duration was short in effective cases. As for doses and treatment duration of IFN, low doses of IFN requires long treatment duration to acquire continuous efficacy and high doses of IFN requires rather short treatment durations. Therefore, early IFN treatment, higher doses and longer periods of IFN treatment may improve the response rate of patients with chronic NANB hepatitis. PMID- 1909273 TI - Prediction of response to interferon in patients with chronic active hepatitis C, and evidence that this improves hepatic metabolic function. AB - We sought to ascertain whether response to alpha interferon treatment could be predicted among patients with chronic active hepatitis C, and whether antipyrine clearance estimations would determine changes in liver function with this disease. The patients came from a randomized controlled trial, with patients who were initially untreated eventually being offered interferon treatment. Among 28 patients treated with interferon 18 (64%) responded with normalization of serum aminotransferase levels. Responders were less likely to have acquired hepatitis C by blood transfusion and more likely to have acquired it by intravenous drug abuse (P less than 0.05). All 13 patients with less severe chronic active hepatitis responded to interferon but only 5 of 15 patients with progressive fibrosis or cirrhosis responded (P less than 0.01). During 8-39 (median 19) months of observation of 16 untreated patients, there was a significant fall in antipyrine clearance (Cl-Ap) but no change in serum albumin. Among interferon treated patients, Cl-Ap improved in 9 of 16 compared with 1 of 14 controls observed for the same time period (P less than 0.02). It is concluded that Cl-Ap is a sensitive test for detecting changes in liver function during chronic hepatitis. Without treatment, deterioration is evident at 18 months in 50% of patients with chronic active hepatitis C. Conversely, normalization of serum aminotransferase levels by interferon is associated with improvement of Cl Ap.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1909274 TI - Prednisolone withdrawal followed by recombinant alfa-interferon in chronic non-A, non-B hepatitis: interim results of a randomized controlled trial. AB - To determine the effect of a recombinant alpha interferon 2b (Intron-A) and possible benefit of prednisolone pretreatment in chronic non-A, non-B hepatitis, 75 Chinese patients with clinico-histologically proven chronic hepatitis were randomly allocated to one of the following regimens: (A) 3 million units of Intron-A trice weekly for 6 months; (B) dose titration according to ALT-AST values; (C) prednisolone withdrawal followed by regimen A; (D) control group: no treatment for 6 months but followed by alternating treatment with 3 million units of Intron-A trice weekly for 2 weeks followed by 2 weeks no treatment for 6 months. Up to September 30, 1990, 67 patients have been followed for a minimum of 2 months. At the end of the second month, complete response (normal ALT) was achieved in 71% of group A, 50% of group B, 50% of group C and 0% of group D. At the end of the 6th month, the complete response rate was 62%, 47% and 64% respectively in groups A, B and C. The response rates in groups A and C were significantly better than the 7% in the control group. Complete response usually (91%) occurred within 2 months after the first dose of interferon. Relapse occurred in 40% of the complete responders, usually within 2 months of the last dose. The cumulative relapse rate was significantly lower in responders of group C (11% vs 43% in group A and 86% in group B during a period of 6 months). Only mild adverse effects were reported though two patients withdrew because of intolerable fatigue.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1909275 TI - Treatment of chronic hepatitis C with weekly administration of interferon-alpha. AB - To evaluate the efficacy of weekly administration of interferon (IFN)-alpha, we studied 23 anti-HCV positive patients with chronic hepatitis diagnosed by liver needle biopsy. Thirteen patients received weekly intramuscular injections of 6 MU human lymphoblastoid interferon (HLBI) for 24 weeks, and the other 10 patients were given no treatment. We examined liver-specific idiotype-bearing antibody (LSIA) in the patients' sera. This HLBI treatment was easily tolerated by all the treated patients. In the treated group serum alanine aminotransferase (ALT) level significantly decreased during HLBI treatment. Normalization of serum ALT level by the end of treatment was observed in 7/13 (54%) of the treated patients but in 0% of the non-treated patients. Anti-HCV was detectable in all the patients during the treatment. Those who had high LSIA levels did not respond to HLBI treatment. These results demonstrate that weekly administration of IFN is sufficient to suppress disease activity in patients with chronic hepatitis C and that patients with high LSIA levels are unlikely to respond to IFN therapy. PMID- 1909276 TI - Isolation and characterization of a temperature-sensitive conditional mutant of Escherichia coli altered for the control of phosphate-regulated proteins. AB - We have identified a conditional mutation which confers a pleiotropic phenotype to Escherichia coli cells: no growth at temperature higher than 36 degrees C, an altered control of the synthesis of several phosphate-regulated polypeptides (including alkaline phosphatase, sn-glycerol-3-phosphate binding protein, phosphate binding protein and outer membrane porin protein PhoE) after growth at 36 degrees C and a wild-type phenotype at 30 degrees C. This mutation was located at minute 89.5 on the E. coli chromosome in a gene we have called cpr for conditional phosphate-regulated. PMID- 1909277 TI - Methanogenic pathways in Methanosphaera stadtmanae. AB - Methanosphaera stadtmanae reduces methanol to CH4 in a similar way as Methanosarcina barkeri. Low activities of 5,10-methylenetetrahydromethanopterin dehydrogenase (MTDH) and reductase (MTR) were found. From studies on formaldehyde oxidation and reduction it was concluded that most likely the inability to reduce CO2 to CH4 was due to the lack of an active or the presence of an inactive CO2 reductase system and methyltetrahydromethanopterin (methyl-H4MPT): coenzyme M methyltransferase. Methanofuran was not detected, while the presence of a pterin, analogous to H4MPT, could be substantiated from its degradation products in boiled extracts. PMID- 1909278 TI - Expression of Staphylococcus aureus enterotoxin type D in Escherichia coli X1776. AB - The Staphylococcus aureus enterotoxin type D was cloned and expressed in Escherichia coli X1776 either as mature toxin or as a fusion with E. coli beta galactosidase. Regulated expression was obtained and levels of toxin produced were in the order of 10(-3)-fold higher than in S. aureus. PMID- 1909279 TI - Improved methods for the detection of beta-galactosidase activity in colonies of Escherichia coli using a new chromogenic substrate: VBzTM-gal (2-(2-(4-(beta-D galactopyranosyloxy)-3-methoxyphenyl)-vinyl)-3- methylbenzothiazolium toluene-4 sulphonate). AB - The use of a new substrate 2-(2-(4-(beta-D-galactopyranosyloxy)-3- methoxyphenyl) vinyl)-3-methylbenzothiazolium toluene-4-sulphonate (VB-zTM-gal) is described for the detection of beta-galactosidase activity in colonies of wild type and mutant strains of Escherichia coli. On enzymic hydrolysis this substrate, which is soluble in water, released a chromophore which is red at pH 7 and bound to cellulose and nitrocellulose. The best procedure for the detection of activity was to grow colonies on standard nitrocellulose membranes (pore size 0.45 microns) laid onto an agar plate and to float the membranes over a solution of the substrate. Coloured colonies developed within 3 min, which were stable at 4 degrees C for several days, and this identified the expression of beta galactosidase activity. This was found to be more specific than methods using triphenyltetrazolium or Eosin Methylene Blue media, and more economical than methods using X-gal (5-bromo-4-chloro-3-indolyl beta-D-galactopyranoside). VBzTM gal should have applications in gene cloning technology and in the detection of coliform organisms in polluted water. PMID- 1909280 TI - Factors that influence the permeability assay of the outer membrane of Pseudomonas aeruginosa. AB - Brief exposure of Pseudomonas aeruginosa to a temperature of 10 degrees C or lower caused a significant leakage of the periplasmic beta-lactamase into the medium. The extent of leakage increased as the incubation temperature was lowered to 4 degrees C and reached a maximum at 0 degrees C. Cells grown in the presence of beta-lactamase inducers were unsuitable for the permeability assay. It was found that the diffusion rates of beta-lactams through the outer membrane of P. aeruginosa were much lower than those previously reported, as assayed under refined conditions. The diffusion rates of beta-lactams in one of the mutants tested were an order of magnitude lower than those of the other strains, despite the fact that the outer membrane protein profile of the strain appeared to be indistinguishable from those of the others. These results suggest that beta lactam antibiotics diffuse through the outer membrane of P. aeruginosa, at least partly, through a non-porin pathway. PMID- 1909281 TI - Transmembrane diffusion of hydrophobic antimicrobial agents and cell surface hydrophobicity in Bacteroides fragilis. AB - The transmembrane diffusion of hydrophobic antimicrobial agents, e.g. lincomycin and clindamycin, was examined in Bacteroides fragilis which is sensitive to these agents. The results showed that these agents penetrate efficiently through the outer membrane. Cell surface hydrophobicity measured by the partition assay between water and p-xylene revealed that the cell surface of B. fragilis is more hydrophobic than that of Salmonella typhimurium or Pseudomonas aeruginosa. Furthermore, treatment with low concentrations of surfactant caused cell lysis. These results suggest that the cell surface hydrophobicity in B. fragilis plays an important role in the efficient transmembrane penetration of hydrophobic compounds. This efficiency explains the susceptibility of B. fragilis to hydrophobic antimicrobial agents. PMID- 1909282 TI - Cefotaxime-hydrolysing activity of the beta-lactamase of Klebsiella oxytoca D488 could be related to a threonine residue at position 140. AB - The chromosomally encoded beta-lactamase of Klebsiella oxytoca D483 strain, active against all third-generation cephalosporins but ceftazidime, was purified to homogeneity. The pure protein was digested by trypsin, Staphylococcus aureus V8 protease or proteinase Asp-N. Amino acid sequences of the HPLC-separated proteolytic peptides were determined by manual Edman degradation. Overlapping fragments gave the alignment of the 263 residues of the beta-lactamase which presented 90% homology with the beta-lactamase of the K. oxytoca E23004 strain and about 40% homology with the other enzymes of the structural class A. The cefotaximase activity might result from interaction of a threonine residue at position 140 (position 165 in the numbering of Ambler) with the oxyimino group of the antibiotic. PMID- 1909283 TI - Mammalian achaete-scute homolog 1 is transiently expressed by spatially restricted subsets of early neuroepithelial and neural crest cells. AB - Using monoclonal antibodies, we have examined the expression pattern of MASH1, a basic helix-loop-helix protein that is a mammalian homolog of the Drosophila achaete-scute proteins. In Drosophila, achaete-scute genes are required for the determination of a subset of neurons. In the rat embryo, MASH1 expression is confined to subpopulations of neural precursor cells. The induction of MASH1 precedes, but is extinguished upon, overt neuronal differentiation. MASH1 is expressed in the forebrain by spatially restricted domains of neuroepithelium and in the peripheral nervous system exclusively by precursors of sympathetic and enteric neurons. The features of early and transient expression, in spatially restricted subpopulations of neural precursors, are similar to those observed for achaete-scute. Thus, the amino acid sequence conservation between MASH1 and achaete-scute is reflected in a parallel conservation of cell type specificity of expression, similar to the case of mammalian MyoD and Drosophila nautilus. These data support the idea that helix-loop-helix proteins may represent an evolutionarily conserved family of cell-type determination genes, of which MASH1 is the first neural-specific member identified in vertebrates. PMID- 1909284 TI - Developmental function of Elf-1: an essential transcription factor during embryogenesis in Drosophila. AB - The Drosophila transcription factor Elf-1 binds to a cis-acting element that is essential for neuronal expression of the Dopa decarboxylase gene (Ddc). Elf-1 also stimulates transcription from the Ddc and Ultrabithorax promoters in vitro. To investigate the function of this factor in vivo we have screened for mutations and identified the Elf-1 gene as grainyhead (grh), a previously known embryonic lethal locus. Elf-1/grh mutations cause late embryonic lethality accompanied by multiple defects in the cuticle and head skeleton. Using Ddc-lacZ gene fusions, we show that these mutations affect Ddc expression in the embryo. Surprisingly, however, epidermal expression is disrupted, whereas neuronal expression remains unaffected. Analysis of the mutant phenotype indicates that Elf-1 coordinately regulates multiple genes involved in the differentiation of epidermal structures. The results highlight the importance of genetic analysis in the study of proteins required for developmental regulation of gene expression. PMID- 1909285 TI - Postheparin plasma diamine oxidase values in the follow up of patients with small bowel Crohn's disease. AB - Measurement of postheparin plasma diamine oxidase (PHD) activity has been proposed to assess mucosal integrity in several diseases of the small intestine. In Crohn's disease, PHD values identify a group of patients with predominantly small bowel mucosal damage. To determine the role of mucosal involvement in the progression of small bowel Crohn's disease and whether different PHD values can predict different outcomes the changes in PHD values in 41 patients with small bowel Crohn's disease admitted consecutively to our department were investigated. The test was performed during periods of active disease and after either medical or surgical treatment had resulted in improvement. PHD values were significantly lower than in normal subjects (normal range 3.7-7.7 U/ml). In 35 patients with active disease (Crohn's disease activity index (CDAI) greater than 150) two groups were identified by choosing a cut off value of 2 U/ml: 93% of the 15 patients with PHD values lower than 2 U/ml (mean (SD) 1.36 (0.46) U/ml) relapsed at least once in the following year, while only the 20% of the 20 whose values were higher than 2 U/ml (mean (SD) 3.69 (1.50)) relapsed in the same period. The data were statistically significant (Yates's corrected chi 2 = 15.63; p less than 0.0001). The positive and negative predictive values of the test were 93% and 80%, respectively. During relapses, PHD values were consistently lower than previous values, and increased significantly after effective medical or surgical treatment. In the six patients in whom there were no changes in disease activity (CDAI persistently less than 150), there was no change in PHD values. This test may be useful for identifying Crohn's disease patients who are likely to relapse. Furthermore, the data indicate that mucosal damage is common in active small bowel Crohn's disease and improves at least in part after treatment. PMID- 1909286 TI - [Persumbran in general practice. Placebo controlled double-blind trial in patients with angina pectoris]. AB - In a randomized double-blind trial performed in 58 offices of internists and general practitioners, Persumbran (25 mg dipyridamole + 10 mg oxazepam) was compared with placebo. A total of 344 patients with mild-to-moderate angina pectoris in whom the tranquilizing effect of oxazepam appeared meaningful and who had already previously been treated with Persumbran, were admitted to the study. In more than 50% of the patients, coronary heart disease had been confirmed by ergometry or angiography. The dose administered during the trial was oriented to the previous treatment with Persumbran. During the first week of the trial, all patients received a placebo; in the following 6 weeks, one group of patients received Persumbran, the other was continued on placebo. If required, nitroglycerine capsules were to be allowed. The patients in the Persumbran group registered an average of 18% fewer "mild", 50% fewer "moderate", and 35% fewer "severe" attacks of angina pectoris; the total number of attacks, weighted for severity, was significantly lower than in the placebo group. The use of nitroglycerine capsules was 39% less in the Persumbran group as compared with the placebo group. Also episodes of "prolonged cardiac complaints whose duration was not exactly definable" were significantly less frequent in the Persumbran group. Moreover, restrictions in activity due to cardiac complaints, as recorded by the patients were significantly fewer in the Persumbran group. PMID- 1909288 TI - Did 1980s legislation slow Medicare spending? PMID- 1909287 TI - IgG-kappa type multiple myeloma in alcoholic cirrhosis--a case report. AB - Transition from polyclonal to monoclonal gammopathy resulted in myeloma in the course of cirrhosis is rare but of interest. We treated such a case of multiple myeloma of IgG-kappa type associated with alcoholic cirrhosis. The case was a 72 year-old Japanese male patient who was admitted because of ascites and edema. Physical examination and laboratory findings including liver histology were compatible with alcoholic cirrhosis. Serum electrophoresis revealed monoclonal hypergammaglobulinemia of IgG-kappa. Bence Jones protein in urine was positive. Bone scintigraphy and roentgenography revealed small punched out lesions in the skull. A bone marrow clot section showed marked infiltration of atypical plasma cells. From these findings multiple myeloma associated with alcoholic cirrhosis was diagnosed. On the basis of a review of the reported cases, the possible relationship between monoclonal gammopathy and chronic liver diseases was discussed. PMID- 1909289 TI - U.S./Canadian health spending: methods and assumptions. PMID- 1909291 TI - New priorities for the Robert Wood Johnson Foundation. PMID- 1909290 TI - Hospital case management: bridging acute and long-term care. PMID- 1909292 TI - The national politics of Oregon's rationing plan. PMID- 1909293 TI - A new policy agenda for home care. PMID- 1909294 TI - [Dislocated neurons and neural network: hodological study of the motor cortex of the reeler mutant mouse]. AB - Reeler, an autosomal recessive mutation in mice, causes cytoarchitectonic abnormalities of cerebral cortex, which are characterized by malposition of neurons. We examined hodological systems of the reeler motor cortex. The results are described as follows. (1) In normal controls, corticospinal tract neurons retrogradely labeled after the injection of HRP ioto the lumbar cord were situated only in layer V (layer of large pyramids: LP). In the reeler, by contrast, the labeled corticospinal tract neurons were scattered diffusely throughout all levels of the corresponding area. (2) In the normal controls, callosal commissural neurons retrogradely labeled after the HRP injection into the motor cortex were distributed in a bilaminar pattern such that the largest number of cells were located in the supragranular layers II (layer of small pyramids; SP) and III (layer of medium pyramids; MP), and in the infragranular layer V (LP). In the reeler mutant mice, callosal commissural neurons were found in all cortical layers, but two-thirds were situated in the lower half of the cortex. (3) In the normal controls, most of the thalamocortical neurons labeled after HRP injection into the motor cortex were located in the ventrolateral nucleus, the lateral division of the ventrobasal nucleus, the central lateral, paracentral and central intralaminar nuclei, and the medial division of the posterior complex. In the reeler mutant mice, retrogradely labeled neurons were again found in the nuclei referred to above, and the distribution pattern and morphology of HRP-filled neurons were also similar to those of normal controls. In the reeler, thalamocortical fibers took an abnormal course within the motor cortex: they ascended obliquely from the white matter to the pial surface and then descended obliquely to the deeper layers. These results strongly suggest that dislocated neurons project correctly to normally-situated and/or abnormally situated target(s). PMID- 1909295 TI - 14;18 translocation in primary intestinal lymphoma: detection by polymerase chain reaction in routinely processed tissue. AB - Chromosomal translocations involving the heavy chain immunoglobulin locus on chromosome 14 and a region on chromosome 18 encoding the bcl-2 gene [t(14;18)] are a characteristic and prevalent chromosomal abnormality in nodal malignant lymphoma, particularly follicular lymphoma. Using the polymerase chain reaction on routinely processed tissue, t(14;18) has been demonstrated in 22% of primary intestinal lymphomas, i.e. in two of nine cases of malignant lymphomatous polyposis, in four of 19 cases of polymorphic B-cell lymphoma and in one of four high-grade unclassified tumours. The findings in this study contradict those of other studies which have shown no such translocation in primary gastric and small intestinal lymphoma. The presence of t(14;18) indicates heterogeneity of molecular abnormalities within histopathologically homogeneous tumours and suggests that caution should be employed in using molecular cytogenetic data to support theories of tumour histogenesis. The low prevalence of this translocation in intestinal lymphoma makes the use of such a methodology as a primary diagnostic aid doubtful, although the technique may help to distinguish primary and secondary lymphoma and could also be used to demonstrate secondary spread. PMID- 1909296 TI - Expression of the intestinal T-lymphocyte associated molecule HML-1: analysis of 75 non-Hodgkin's lymphomas and description of the first HML-1 positive T lymphoblastic tumour. AB - The expression of the gut intra-epithelial T-cell associated molecule HML-1, a trimeric protein of 150, 125, 105 kD, was studied in 75 T-cell lymphomas of different subtypes: 20 T-lymphoblastic lymphomas/leukaemias; 50 nodal peripheral T-cell lymphomas; and five intestinal T-cell lymphomas. Our results confirm: (i) the usefulness of the HML-1 monoclonal antibody as an immunohistochemical marker for intestinal T-cell lymphomas: and (ii) the lack of reactivity of HML-1 with nodal peripheral T-cell lymphomas. Moreover, expression of the HML-1 molecule was found for the first time in a case of T-lymphoblastic lymphoma/leukaemia. The patient presented with a mediastinal mass which consisted of HML-1 + neoplastic cells displaying a phenotypic profile consistent with early thymocytes. Genes coding for the alpha, beta, gamma and delta chains of the T-cell receptor were in a germline configuration. The neoplastic cells could have been derived from the small subset of HML-1 + thymocytes detectable in the cortex of normal human thymus. PMID- 1909297 TI - Managing the pharmacy becomes more complex. PMID- 1909298 TI - Hospitals measure pharmacy computer benefits. PMID- 1909299 TI - Natural antibodies to 65 kD mycobacterial heat shock protein in rats do not correlate with susceptibility for Mycobacterium tuberculosis induced adjuvant arthritis. AB - Natural antibodies to 65 kD heat shock protein (hsp65) of Mycobacterium bovis were found in the sera of Lewis rats. The levels of these natural hsp65 antibodies differed substantially between the individual rats. Each rat was subsequently tested for its susceptibility to develop arthritis following injection of M. tuberculosis in incomplete Freund adjuvant. It was found that the incidence and severity of the induced arthritis did not differ between groups of Lewis rats with relatively high and relatively low natural antibody levels to hsp65. Inoculation of rats without natural antibodies to hsp65 with intestinal contents did not induce hsp65 antibodies, although the rats were able to respond to the antigen. PMID- 1909300 TI - Distribution of MEL-14+ cells in various lymphoid tissues. AB - The distribution of MEL-14+ lymphocytes was investigated by both fluorocytometric analysis and complement-dependent-cellular-cytotoxicity (CDCC) tests in which rabbit anti-rat Ig was added with complement at a secondary step. When CDCC was employed to detect MEL-14+ cells, almost half of the thymocytes were found to be MEL-14+ in various strains of mice. This high proportion of MEL-14+ cells stands in striking contrast to prior reports. Furthermore, when determined by fluorocytometric analysis, MEL-14+ cells were found to comprise more than 80% of the cells in the thymus. The MEL-14+ thymocytes comprised both immature subsets (CD4-8-, CD4+8+) and mature subsets (CD+8-, CD4-8+). MEL-14 brightly positive (MEL-14high) cells, however, were located mainly in mature T cell subpopulations within the thymus. The MEL-14high thymocytes appeared to be susceptible to the CDCC method. Most of MEL-14+ cells present in spleens and lymph nodes were shown to be included in the MEL-14high population. The MEL-14+ cells susceptible to treatment with MEL-14, rabbit anti-rat Ig plus complement in the spleen and lymph node were restricted to cells of the T-lineage. These data suggest that T cells may change from cells with low expression of the MEL-14 antigens at their surface to cells with high MEL-14 antigens in the process of differentiation. Furthermore, these findings indicate that MEL-14 molecules may be used as a surface marker to characterize an important T cell subpopulation. PMID- 1909301 TI - Effect of TNF priming of murine peritoneal macrophages on their activation to a tumoricidal state. AB - Murine peritoneal macrophages, on treatment with TNF (10 U/ml) for various durations, showed enhanced cyototoxicity against tumor target cells. The macrophage-mediated cytotoxicity was significantly enhanced when TNF-primed macrophages were treated with cisplatin, LPS, FK-565 or interferon-gamma for 24 h, compared to unprimed and treated macrophages. TNF-primed macrophages also showed enhanced expression of interleukin-1 and tumor necrosis factor activities on activation with different biological response modifiers. PMID- 1909302 TI - Germline transcripts of the immunoglobulin heavy-chain and T cell receptor genes in a murine hematopoietic stem cell line LyD9 and its derivative cell lines. AB - We compared germline transcript levels of immunoglobulin heavy chain and T cell receptor (TcR) genes in a murine hematopoietic stem cell line, LyD9, and its derivative cell lines. LyD9 cells can be induced to differentiate into at least three lineages, namely, B lymphocyte, macrophage, and granulocyte lineages. Although C mu transcripts were found in stem cells to B lymphocytes, other myeloid-committed cells also expressed significant amounts of C mu transcripts. Germline TcR transcripts did not show good correlation with differentiation potential and stages of hematopoietic cells. During this search we identified a novel germline transcript containing the JH-C microliter sequence in LyD9 and some of its derivative cells. Expression of mRNAs for immunoglobulin- and TcR associated molecules (lambda 5, MB1 and CD3 delta) was widespread except for lambda 5 mRNA. Among three mRNAs encoding putative recombinase proteins, RAG-1 and RAG-2 mRNAs were not expressed in any cell lines tested, while RBP-2 mRNA was expressed ubiquitously. PMID- 1909303 TI - Increased endogenous interferon-gamma and neopterin correlate with increased degradation of tryptophan in human immunodeficiency virus type 1 infection. AB - Reduced tryptophan and increased kynurenine concentrations have been reported in patients with human immunodeficiency virus type 1 (HIV-1) infection. From in vitro data it appears that activated indoleamine 2,3-dioxygenase (IDO) is involved in this metabolic change. IDO is inducible by interferon-(IFN)-gamma. We compared serum concentrations of IFN-gamma and neopterin (the biosynthesis of which is also inducible by IFN-gamma) with serum, tryptophan and kynurenine of 42 patients with HIV-1 infection. IFN-gamma, neopterin and kynurenine levels were significantly increased compared to HIV-1 seronegative controls whereas tryptophan was significantly decreased. Various significant correlations were found between tryptophan, kynurenine, IFN-gamma and neopterin concentrations. Highest degree of correlation was found between neopterin, IFN-gamma and the kynurenine per tryptophan quotient which is the ratio between the product and the substrate concentration of IDO. The data indicate that decreased tryptophan in HIV-1 seropositives may result from chronic immune activation and can be referred to increased activation of IDO. PMID- 1909305 TI - Potentiation of the baroreceptor-heart rate reflex by sympathectomy in conscious rats. AB - In both animals and humans, stimuli leading to sympathetic activation are accompanied by an impairment of the baroreceptor-heart rate reflex. To determine whether sympathetic activity normally interferes with this reflex function we examined in conscious Wistar-Kyoto (WKY) rats the effect of chemical sympathectomy by 6-hydroxydopamine on the bradycardic response to baroreceptor stimulation induced by raising blood pressure via intravenous phenylephrine boluses; control rats received vehicle. Spontaneously hypertensive rats were also studied because in these animals there is both a baroreceptor reflex impairment and a sympathetic overactivity. Baroreceptor reflex sensitivity, calculated as the ratio of the peak increase in pulse interval to the peak increase in mean arterial pressure, was 75% greater in sympathectomized WKY rats than in control WKY rats (1.28 +/- 0.15 versus 0.73 +/- 0.10 msec/mm Hg, mean +/- SEM; p less than 0.01). The sympathectomy-induced increase in sensitivity was even larger in spontaneously hypertensive rats (SHR) (1.26 +/- 0.12 versus 0.44 +/- 0.06 msec/mm Hg in sympathectomized SHR versus control SHR, +186%; p less than 0.01) so that the impaired baroreceptor reflex sensitivity observed in control SHR as compared with control WKY rats (-40%, p less than 0.01) was no longer detectable in the sympathectomized groups. To establish whether the sympathectomy-induced potentiation of the reflex was due to an increase in cardiac responsiveness to vagal stimuli, we subjected separate groups of anesthetized, vagotomized SHR and WKY rats to graded electrical stimulation of the right efferent vagus. The bradycardic effects of vagal stimulation, however, were similar in sympathectomized and control animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1909304 TI - Cellular mechanism of endothelin-1 release by angiotensin and vasopressin. AB - Release of endothelin-1, a novel potent vasoconstrictor peptide originally isolated from endothelial cells, from cultured bovine endothelial cells has been shown to be stimulated by arginine vasopressin and angiotensin II. To elucidate the cellular mechanism by which endothelin-1 is released by these vasoconstrictors, we tested the effects of several compounds on the agonist induced endothelin-1 release and studied the changes of cytosolic free Ca2+ concentrations and phosphoinositide breakdown by these agonists in cultured bovine endothelial cells. Protein kinase C inhibitors (H-7, staurosporine), an intracellular Ca2+ chelator, and an inhibitor of phospholipase C (neomycin), all abolished the agonist-induced endothelin-1 release, whereas the Ca2+ channel blocker nicardipine was ineffective. Although synthetic 1,2-diglyceride (diolein) dose dependently stimulated endothelin-1 release, downregulation of protein kinase C after pretreatment with phorbol ester resulted in decreased effects to increase endothelin-1 release by the agonists. Both arginine vasopressin and angiotensin II induced immediate and transient increases in intracellular Ca2+ levels of fura-2-loaded endothelial cells as well as formation of inositol trisphosphate; the agonist-induced intracellular Ca2+ increases were not affected either by nicardipine or by chelating extracellular Ca2+. The arginine vasopressin- and angiotensin II-induced intracellular Ca2+ increases, inositol trisphosphate formation, and endothelin-1 release were completely abolished by V1 receptor antagonist and saralasin, respectively. It is concluded that arginine vasopressin and angiotensin II stimulate the release of endothelin-1 by a common mechanism, involving receptor-mediated mobilization of intracellular Ca2+ and activation of protein kinase C in endothelial cells. PMID- 1909306 TI - Adult respiratory distress syndrome (ARDS) complicating meningococcaemia. AB - We describe a one year old boy with meningococcaemia complicated by the adult respiratory distress syndrome. Maintenance of oxygenation required a positive end expiratory pressure of 20 cm H2O. Resultant barotrauma produced pneumothorax and pneumomediastinum. Prompt recognition and treatment of this complication can reduce its high mortality rate. PMID- 1909307 TI - Mechanisms of PCBs mixture toxicity on isolated rat hepatocytes. AB - Exposure of isolated hepatocytes to a polychlorinated biphenyl mixture induced a rapid loss of cell viability. The effect was not dose-dependent. The biochemical effects in the cellular toxicity did not involve glutathione content, protein sulfhydryl groups and lipid peroxidation. A transient increase in cytosolic Ca2+ was observed after exposing the hepatocytes to the polychlorinated biphenyl mixture. Our findings indicate that polychlorinated biphenyls are able to kill hepatocytes and suggest that elevation of cytosolic Ca2+ concentration could be responsable of the toxicity. PMID- 1909308 TI - Demographic data and treatment of small companion animals with lead poisoning: 347 cases (1977-1986). AB - Three hundred forty-seven cases of lead poisoning in small animals, diagnosed after 1976, were reviewed. The types of treatments used and their outcomes were analyzed. Changes in blood lead concentrations following various treatments, as well as the sources of lead exposure, were also reviewed. The geographic origins of the cases were traced, and demographic factors were studied to determine possible correlates that might explain the regional distribution of cases. PMID- 1909309 TI - Reduction in age of puberty in gilts consuming melatonin during decreasing or increasing daylength. AB - Two experiments were conducted to determine whether oral administration of melatonin alters the onset of puberty in gilts during naturally increasing or decreasing daylength. In Exp. 1, 20 crossbred prepubertal gilts weighing 77.5 +/- .5 kg at 171.8 +/- 1.0 d of age were assigned randomly to receive either a daily oral dose of 3 mg of melatonin (MEL) or ethanol vehicle (ETH) at 1530 from August 31 to December 1, 1987 (decreasing daylength). Gilts were exposed to mature boars for 20 min thrice weekly and blood samples were collected twice weekly. Serum concentrations of progesterone were used to establish age at puberty and length of estrous cycle. In Exp. 2, 20 crossbred prepubertal gilts weighing 67.7 +/- .7 kg at 143.8 +/- 1.1 d of age received either MEL or ETH treatment from February 1 to May 15, 1988 (increasing daylength). Age of puberty was less in gilts that received MEL than in gilts that received ETH in both Exp. 1 (198 +/- 3 vs 228 +/- 7 d; P less than .01) and Exp. 2 (183.8 +/- 2.7 d vs 194.3 +/- 3.3 d; P less than .05). Gilts that received MEL reached puberty at a lighter weight than gilts that received ETH in Exp. 1 (95.6 +/- 2.1 vs 112.4 +/- 3.9 kg; P less than .01) and Exp. 2 (88.1 +/- 1.5 vs 96.0 +/- 1.8 kg; P less than .01). Serum concentrations of LH and FSH, length of estrous cycles, and percentage of muscle of carcasses were similar between MEL and ETH gilts.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1909310 TI - Effect of dietary cholesterol and carbohydrate on small intestinal structure and function in prematurely weaned rats. AB - A study using the prematurely weaned rat as a model for the pig was undertaken to determine the effect of dietary cholesterol and carbohydrate source on small intestinal structure and function. Duodenal and jejunal samples were obtained at 18, 24, and 30 d of age from rats weaned at 15 d of age and from unweaned rats at 15, 18, 24, and 30 d of age. Four 20% CP diets were formulated: two diets used lactose and glucose as the carbohydrate source and two used sucrose and starch as the carbohydrate source; 1% cholesterol was substituted for either glucose or starch in one of each diet type. The unweaned rats consistently gained weight at a faster rate (P less than .01), had greater concentrations of Alcian blue (AB+) and periodic acid-Schiff (PAS+) goblet cells (P less than .03), and had more favorable villus height than did the weaned rats. The animals fed cholesterol tended to gain more weight, had more AB+ and PAS+ goblet cells (P less than .03), and had longer villi than did those not fed cholesterol. Lactase activities tended to be greater in the unweaned rats. Sucrase activities were greater in the weaned rats at 18 d (P less than .02). The data indicate that the addition of cholesterol to weaning diets is beneficial in maintaining small intestinal integrity. PMID- 1909311 TI - Effects of carbon dioxide and sub-lethal levels of antibiotics on adherence of coagulase-negative staphylococci to polystyrene and silicone rubber. AB - Fifty coagulase-negative staphylococci (CNS) strains were investigated for adherence to both silicone rubber and polystyrene using a microtitre tray system. Culture in an atmosphere containing a physiological level of carbon dioxide (5% CO2) profoundly affected adherent growth to both surfaces. Most strains adhered less well in this atmosphere compared to in air alone, with mean reductions in adherence of 84% and 86% to silicone rubber and polystyrene respectively. Occasional strains adhered better in 5% CO2. The effects of antibiotic concentrations equivalent to 1/4 MIC of cefuroxime, ciprofloxacin, vancomycin and teicoplanin on the adherence of 10 CNS strains were also studied. Vancomycin and teicoplanin frequently increased adherence to silicone rubber and polystyrene compared to controls. The effects of antibiotics on adherence were not only strain dependent but also sometimes atmosphere or surface specific. Antibiotic induced changes in adherence did not appear to correlate with changes in strain protein profiles or surface hydrophobicities. PMID- 1909312 TI - Cyclooxygenase pathway mediates lung injury induced by phorbol and platelets. AB - The role of platelets in lung injury has not been well defined. In the present study of isolated perfused rat lungs, phorbol myristate acetate (PMA; 0.15 microgram/ml) or platelets (6.7 X 10(4)/ml) alone did not discernibly change the pulmonary arterial pressure (PAP) or lung weight (LW). However, the combination of platelets and PMA drastically increased the PAP and LW (delta PAP 26.2 +/- 1.0 mmHg, delta LW 2.7 +/- 0.4 g). delta PAP was positively correlated with the increase in thromboxane B2 produced by infusion of platelets and PMA (thromboxane B2 = 35.6 + 0.97 delta PAP, r = 0.67, P less than 0.01). The hypertension and edema formation induced by PMA and platelets were strongly attenuated by indomethacin, an inhibitor of platelet cyclooxygenase (delta PAP 5.6 +/- 2.0 mmHg, P less than 0.001; delta LW 0.0 +/- 0.1 g, P less than 0.001), and by imidazole, an inhibitor of thromboxane A2 synthase (PAP 8.0 +/- 2.5 mmHg, P less than 0.001; LW 0.0 +/- 0.3 g, P less than 0.01). Inactivation of platelet lipoxygenase with nordihydroguaiaretic acid mildly depressed pulmonary pressure but did not affect delta LW (delta PAP 18.9 +/- 1.6 mmHg, P less than 0.05; delta LW 3.1 +/- 0.3 g, P greater than 0.05). In vitro experiments showed that the capacity of platelets to release oxygen radicals was only 2.6% of that found for granulocytes. These results suggest that platelets may be activated by PMA to increase PAP and vascular permeability.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1909313 TI - Interaction between CO2 concentration and flow rate on peripheral airway resistance. AB - In the present study, we investigated the interaction between CO2 concentration and rate of delivered flow on peripheral airway resistance (Rp) in the intact canine lung. Dogs were anesthetized, intubated, paralyzed, and mechanically ventilated with room air to maintain end-tidal CO2 between 4.8 and 5.2%. Using a wedged bronchoscope technique, we measured Rp at functional residual capacity. The relationship between CO2 concentration and Rp was measured at flow rates of 100 and 400 ml/min with 5, 3, 2, 1, and 0% CO2 in air. Measurements were made at the end of a 3-min exposure to each gas. At low flow rates (100 ml/min) responses to hypocapnia were small, whereas at high flow rates (400 ml/min) responses were large. The PC50 (defined as the CO2 concentration required to produce a 50% increase in Rp above baseline Rp established on 5% CO2) at 400 ml/min (1.73%) was significantly larger than that at 100 ml/min (0.38%). We also directly measured the relationship between Rp and flow rate with 5% CO2 (normocapnia) or 1% CO2 (hypocapnia) delivered into the wedged segment. Increases in normocapnic flow caused small but significant decreases in Rp. In contrast, increases in hypocapnic flow from 100 to 400 ml/min caused a 108% increase in Rp. Thus the response to hypocapnia is augmented by increasing flow rate. This interaction can be explained by a simple model that considers the effect of local ventilation perfusion ratio and gas mixing on the local CO2 concentration at the site of peripheral airway contraction. PMID- 1909314 TI - Effects of CO2 rebreathing on pulmonary mechanics in premature infants. AB - The effects of hypercapnia produced by CO2 rebreathing on total pulmonary, supraglottic, and lower airway (larynx and lungs) resistance were determined in eight premature infants [gestational age at birth 32 +/- 3 (SE) wk, weight at study 1,950 +/- 150 g]. Nasal airflow was measured with a mask pneumotachograph, and pressures in the esophagus and oropharynx were measured with a fluid-filled or 5-Fr Millar pressure catheter. Trials of hyperoxic (40% inspired O2 fraction) CO2 rebreathing were performed during quiet sleep. Total pulmonary resistance decreased progressively as end-tidal PCO2 (PETCO2) increased from 63 +/- 23 to 23 +/- 15 cmH2O.l-1.s in inspiration and from 115 +/- 82 to 42 +/- 27 cmH2O.l-1.s in expiration between room air (PETCO2 37 Torr) and PETCO2 of 55 Torr (P less than 0.05). Lower airway resistance (larynx and lungs) also decreased from 52 +/- 22 to 18 +/- 14 cmH2O.l-1.s in inspiration and from 88 +/- 45 to 30 +/- 22 cmH2O.l 1.s in expiration between PETCO2 of 37 and 55 Torr, respectively (P less than 0.05). Resistance of the supraglottic airway also decreased during inspiration from 7.2 +/- 2.5 to 3.6 +/- 2.5 cmH2O.l-1.s and in expiration from 7.6 +/- 3.3 to 5.3 +/- 4.7 cmH2O.l-1.s at PETCO2 of 37 and 55 Torr (P less than 0.05). The decrease in resistance that occurs within the airway in response to inhaled CO2 may permit greater airflow at any level of respiratory drive, thereby improving the infant's response to CO2. PMID- 1909316 TI - Effect of hyperventilation on oxygenation of the brain cortex of newborn piglets. AB - A new phosphorescence imaging method (Rumsey et al. Science Wash. DC 241: 1649 1651, 1988) has been used to continuously monitor the PO2 in the blood of the cerebral cortex of newborn pigs. A window was prepared in the skull and the brain superfused with artificial cerebrospinal fluid. The phosphorescent probe for PO2, Pd-meso-tetra(4-carboxyphenyl)porphine, was injected directly into the systemic blood. The phosphorescence of the probe was imaged, and the lifetimes were measured using flash illumination and a gated video camera. The PO2 in the blood of the veins and capillary beds of the cortex was calculated from the lifetimes. Systemic blood pressure was continuously monitored while the systemic arterial PCO2, PO2, and blood pH were measured periodically. The PO2 in the blood was quantitated for 60- to 200 microns2 regions within the image (from a total field of approximately 3 mm diam). The PO2 in the microvasculature was not uniform across the viewing field but increased or decreased in each region independently of the other regions. Thus at any point in time the PO2 in a region could be substantially above or below the average value. During hyperventilation, which lowered arterial PCO2 and increased pH of the blood, the average PO2 decreased in proportion to the decrease in arterial PCO2. For example, hyperventilation, which decreased arterial PCO2 from its normal value of 40 Torr to 10 Torr, caused a rapid (within 5 min) decrease in PO2 in the blood of capillaries and veins to approximately one-third of normal. PMID- 1909315 TI - Ventilatory compensation for lactacidosis in ponies: role of carotid chemoreceptors and lung afferents. AB - We investigated changes in arterial PCO2 (PaCO2) and pulmonary ventilation (VE) in normal, carotid chemoreceptor-denervated, and hilar nerve-denervated ponies during intravenous lactic acid infusion at rest and treadmill exercise at 1.8 mph 5% grade (mild) and 1.8 mph-15% grade (moderate). Lactic acid, (0.5 M) infusion of 0.10, 0.13, and 0.20 ml.min-1.kg-1 at rest and mild and moderate exercise increased arterial [H+] linearly throughout the 10 min of acid infusion. At 10 min of infusion, arterial [H+] had increased approximately 20 nmol/l (0.2 pH units) for each condition and group. Under most conditions, the temporal pattern of PaCO2 during acid infusion was biphasic. At rest and during mild exercise in all groups, and in carotid chemoreceptor-denervated ponies during moderate exercise, PaCO2 increased approximately 2 Torr (P less than 0.05) during the first 2 min of acid infusion. However, in normal ponies during moderate exercise, PaCO2 was not changed from control in the first 2 min of infusion. Between 2 and 10 min of infusion at rest and mild and moderate exercise in all groups, there was a 5-Torr significant decrease in PaCO2, which did not differ (P greater than 0.10) between groups. VE increased between 15-30 s and 2 min of infusion, but VE changed minimally between 2 and 10 min of infusion at rest and exercise in all groups of ponies. We conclude that lactacidosis does increase VE at rest and submaximal exercise in the pony.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1909317 TI - Epilepsy and craniofacial abnormalities. PMID- 1909318 TI - Distribution of compatible solutes in the halophilic methanogenic archaebacteria. AB - Accumulation of compatible solutes, by uptake or de novo synthesis, enables bacteria to reduce the difference between osmotic potentials of the cell cytoplasm and the extracellular environment. To examine this process in the halophilic and halotolerant methanogenic archaebacteria, 14 strains were tested for the accumulation of compatible solutes in response to growth in various extracellular concentrations of NaCl. In external NaCl concentrations of 0.7 to 3.4 M, the halophilic methanogens accumulated K+ ion and low-molecular-weight organic compounds. beta-Glutamate was detected in two halotolerant strains that grew below 1.5 M NaCl. Two unusual beta-amino acids, N epsilon-acetyl-beta-lysine and beta-glutamine (3-aminoglutaramic acid), as well as L-alpha-glutamate were compatible solutes among all of these strains. De novo synthesis of glycine betaine was also detected in several strains of moderately and extremely halophilic methanogens. The zwitterionic compounds (beta-glutamine, N epsilon acetyl-beta-lysine, and glycine betaine) and potassium were the predominant compatible solutes among the moderately and extremely halophilic methanogens. This is the first report of beta-glutamine as a compatible solute and de novo biosynthesis of glycine betaine in the methanogenic archaebacteria. PMID- 1909319 TI - Altered phosphorylation of Bacillus subtilis DegU caused by single amino acid changes in DegS. AB - The Bacillus subtilis sacU locus consists of the degS and degU genes, which play a major role in controlling the production of degradative enzymes including extracellular proteases. DegS has been shown to be autophosphorylated and to transfer the phosphoryl group to DegU. In this study, we partially purified the DegS proteins which carry amino acid changes resulting from various mutations and examined the phosphorylation reaction. The mutations used were degS42, causing a reduction in exoprotease production, and degS100(Hy) and degS200(Hy), causing overproduction of the enzymes. The following results were obtained. The DegS protein derived from degS42 was deficient in both autophosphorylation and subsequent phosphate transfer to DegU. Compared with wild-type DegS, the DegS proteins derived from the overproduction mutations, degS100(Hy) and degS200(Hy), were less active in the autophosphorylation and phosphorylation of DegU. However, the DegU phosphates produced by the mutant DegS proteins were more stable than that produced by the wild-type DegS. These results suggest that phosphorylation is tightly linked to exoprotease production and that the prolonged retention of the phosphoryl moiety on DegU activates the genes for the extracellular proteases. It was also shown that the rate of dephosphorylation of DegU-phosphate was increased as the amount of DegS was increased. All of these results suggest that DegS is involved in the dephosphorylation of DegU-phosphate. PMID- 1909320 TI - Molecular cloning of genes involved with expression of A-band lipopolysaccharide, an antigenically conserved form, in Pseudomonas aeruginosa. AB - Most strains of Pseudomonas aeruginosa can express two chemically and immunologically distinct types of lipopolysaccharide (LPS), an antigenically conserved form called A band and the serotype-specific form called B band. To study the molecular controls regulating expression of the A-band LPS antigen, we have cloned the genes involved with A-band LPS expression. Strain AK1401, a phage resistant mutant of PAO1 which was shown previously to produce only A-band LPS and not the O-antigen-containing B-band LPS, was mutagenized by using ethyl methanesulfonate to generate an A-band-deficient mutant called rd7513. A cosmid clone bank of P. aeruginosa PAO1 whole genomic DNA was constructed in Escherichia coli. The gene bank was mobilized en masse into strain rd7513, and detection of complementation of synthesis of A band was done by screening transconjugants in a colony immunoblot assay with the A-band-specific monoclonal antibody N1F10. One recombinant cosmid, pFV3, complemented synthesis of A-band polysaccharide in rd7513. Silver-stained polyacrylamide gel and Western immunoblot analyses of LPS extracted from the transconjugant rd7513(pFV3) showed that the A band produced had a higher molecular weight than the A band of AK1401. Analysis of the plasmid pFV3 showed that it contained a chromosomal insert of 27 kb. Two subclones of pFV3, namely, pFV35 and pFV36, containing chromosomal inserts of 5.3 and 4.2 kb, respectively, also complemented A-band expression in rd7513. The LPS banding profile of rd7513(pFV35) was similar to that of AK1401, while the LPS profile of rd7513(pFV36) more closely resembled that of rd7513(pFV3). pFV3 complemented A band expression in five of the six P. aeruginosa O serotypes which lack A band as well as in rough strain AK44 but failed to complement A-band expression in core mutants AK1012 and AK1282, suggesting that pFV3 contains genes for A-band expression and that synthesis of a complete core region in isogenic mutant strains is required for A-band synthesis. PMID- 1909321 TI - Novel structure of the recA locus of Mycobacterium tuberculosis implies processing of the gene product. AB - A fragment of Mycobacterium tuberculosis DNA containing recA-like sequences was identified by hybridization with the Escherichia coli recA gene and cloned. Although no expression was detected from its own promoter in E. coli, expression from a vector promoter partially complemented E. coli recA mutants for recombination, DNA repair, and mutagenesis, but not for induction of phage lambda. This clone produced a protein which cross-reacts with antisera raised against the E. coli RecA protein and was approximately the same size. However, the nucleotide sequence of the cloned fragment revealed the presence of an open reading frame for a protein about twice the size of other RecA proteins and the cloned product detected by Western blotting (immunoblotting). The predicted M. tuberculosis RecA protein sequence was homologous with RecA sequences from other bacteria, but this homology was not dispersed; rather it was localized to the first 254 and the last 96 amino acids, with the intervening 440 amino acids being unrelated. Furthermore, the junctions of homology were in register with the uninterrupted sequence of the E. coli RecA protein. Identical restriction fragments were found in the genomic DNAs of M. tuberculosis H37Rv and H37Ra and of M. bovis BCG. It is concluded that the ancestral recA gene of these species diversified via an insertional mutation of at least 1,320 bp of DNA. Possible processing mechanisms for synthesizing a normal-size RecA protein from this elongated sequence are discussed. PMID- 1909322 TI - Identification of an alternative nitrogenase system in Rhodospirillum rubrum. AB - A second nitrogenase activity has been demonstrated in Rhodospirillum rubrum. This nitrogenase is expressed whenever a strain lacks an active Mo nitrogenase because of physiological or genetic inactivation. The alternative nitrogenase is able to support growth on N2 in the absence of fixed N. V does not stimulate, nor does Mo or W inhibit, growth or activity under the conditions tested. The proteins responsible for this activity were identified by electrophoretic and immunological properties. The synthesis of these proteins was repressed by NH4+. The alternative nitrogenase reductase is ADP ribosylated in response to darkness by the system that regulates the activity of the Mo nitrogenase. The genes for the alternative nitrogenase have been cloned, and the alternative nitrogenase reductase has been expressed in an in vitro transcription-translation system. PMID- 1909323 TI - Structural features of methyl-accepting taxis proteins conserved between archaebacteria and eubacteria revealed by antigenic cross-reaction. AB - A number of eubacterial species contain methyl-accepting taxis proteins that are antigenically and thus structurally related to the well-characterized methyl accepting chemotaxis proteins of Escherichia coli. Recent studies of the archaebacterium Halobacterium halobium have characterized methyl-accepting taxis proteins that in some ways resemble and in other ways differ from the analogous eubacterial proteins. We used immunoblotting with antisera raised to E. coli transducers to probe shared structural features of methyl-accepting proteins from archaebacteria and eubacteria and found substantial antigenic relationships. This implies that the genes for the contemporary methyl-accepting proteins are related through an ancestral gene that existed before the divergence of arachaebacteria and eubacteria. Analysis by immunoblot of mutants of H. halobium defective in taxis revealed that some strains were deficient in covalent modification of methyl-accepting proteins although the proteins themselves were present, while other strains appeared to be missing specific methyl-accepting proteins. PMID- 1909325 TI - Factors influencing the specific interaction of Neisseria gonorrhoeae with transforming DNA. AB - The specific interaction of transformable Neisseria gonorrhoeae with DNA depends on the recognition of specific 10-residue target sequences. The relative affinity for DNA between 3 and 17 kb in size appears to be linearly related to the frequency of targets on the segment and is unaffected by absolute size. The average frequency of targets in chromosomal DNA of N. gonorrhoeae appears to be approximately one per 1,000 bp. PMID- 1909324 TI - The cysP promoter of Salmonella typhimurium: characterization of two binding sites for CysB protein, studies of in vivo transcription initiation, and demonstration of the anti-inducer effects of thiosulfate. AB - The cysPTWA operons of Escherichia coli and Salmonella typhimurium encode components of periplasmic transport systems for sulfate and thiosulfate and are regulated as part of the cysteine regulons. In vitro transcription initiation from the cysP promoter was shown to require both CysB protein and either O-acetyl L-serine or N-acetyl-L-serine, which act as inducers, and was inhibited by the anti-inducer sulfide. Thiosulfate was found to be even more potent than sulfide as an anti-inducer. DNase I protection experiments showed two discrete binding sites for CysB protein in the presence of N-acetyl-L-serine. CBS-P1 is located between positions -85 and -41 relative to the major transcription start site, and CBS-P2 is located between positions -19 and +25. Without N-acetyl-L-serine, the CysB protein protected the region between positions -63 and -11, which was designated CBS-P3. In gel mobility shift assays, the mobility of CysB protein cysP promoter complexes was increased by O-acetyl-L-serine, N-Acetyl-L-serine had no effect in gel shift experiments, presumably because its anionic charge results in its rapid removal from the complex during electrophoresis. Comparison of DNA fragments differing with respect to binding site position indicated that complexes with CysB protein contain DNA that is bent somewhere between CBS-P1 and CBS-P2 and that O-acetyl-L-serine decreases DNA bending. Binding studies with fragments containing either CBS-P2 alone, CBS-P1 alone, or the entire cysP promoter region suggest a model in which the complex of bent DNA observed in the absence of O-acetyl-L-serine contains a single CysB protein molecule bound to CBS P3. At relatively low CysB protein concentrations, O-acetyl-L-serine would cause a single CysB protein molecule to bind tightly to CBS-P1, rather than to CBS-P3, thereby decreasing DNA bending and increasing complex electrophoretic mobility. At higher CysB protein concentrations, O-acetyl-L-serine would cause a second molecule to bind at CBS-P2, giving a more slowly migrating complex. PMID- 1909326 TI - An interleukin 1 beta point mutant demonstrates that jun/fos expression is not sufficient for fibroblast metalloproteinase expression. AB - Substitution of glycine for arginine at position 127 of the mature human interleukin 1 beta protein generates a mutant IL-1 beta protein (IL-1 beta R--- G) which binds cellular IL-1 receptors with high affinity but fails to elicit significant proliferation of T-helper cells (Gehrke, L., Jobling, S. A., Paik, L. S. K., McDonald, B., Rosenwasser, L. J., and Auron, P. E. (1990) J. Biol. Chem. 265, 5922-5925). Although both IL-1 beta and the IL-1 beta R----G mutein stimulate transcription of fibroblast immediate early (fos and jun) and early (IL 1 beta and IL-6) genes, the IL-1 beta R----G mutein, in contrast to the wild-type IL-1 beta protein, induces minimal or no transcription of late genes such as procollagenase and prostromelysin. The effect of the naturally occurring IL-1 receptor antagonist protein (IL-1ra) on fibroblast transcription is distinct from that of the IL-1 beta R----G mutein, for the IL-1ra fails to stimulate not only late (procollagenase and prostromelysin) but also immediate early (fos and jun) gene expression. These data suggest that the IL-I beta R----G mutein triggers an incomplete or defective signal transduction cascade and demonstrate that fibroblast fos and jun expression is not necessarily accompanied by increased transcription of genes containing the AP-1 binding site. These data also suggest that at least two events are required for IL-1-mediated late gene induction in fibroblasts. PMID- 1909327 TI - Insulin-activated protein kinases phosphorylate a pseudosubstrate synthetic peptide inhibitor of the p70 S6 kinase. AB - p70 S6 kinase, a major insulin-mitogen-activated ribosomal S6 protein kinase in mammalian cells, is activated by phosphorylation of multiple Ser/Thr residues on the enzyme polypeptide. A synthetic peptide, corresponding to a 37-residue segment from the carboxyl-terminal tail of the kinase which resembles the sequence phosphorylated in S6, acts as a competitive inhibitor of p70 S6 kinase without itself being phosphorylated by the enzyme. This synthetic peptide is phosphorylated by an array of protein kinases which are rapidly activated by insulin. Thus, these sequences of p70 S6 kinase constitute a potential autoinhibitory pseudosubstrate site, whose phosphorylation is catalyzed by candidate upstream-activating protein kinases. PMID- 1909328 TI - Structure and expression of the infA operon encoding translational initiation factor IF1. Transcriptional control by growth rate. AB - The cellular levels of the three translational initiation factors, IF1, IF2, and IF3, increase as a function of growth rate in parallel with those of ribosomes. Therefore both ribosomal and initiation factor gene expression is under metabolic control. To address how expression of the Escherichia coli gene for IF1, infA, is regulated, a 3-kilobase region of the genome surrounding infA was sequenced. The 5' and 3' termini of in vivo infA transcripts were defined by S1 nuclease mapping, and mRNA size was measured by Northern blot hybridization. The infA gene is transcribed by two promoters, P1 and P2, which generate transcripts of 525 and 330 nucleotides, apparently ending at the same rho-independent terminator. Analyses of operon and protein fusions to lacZ demonstrate that neither infA transcription nor translation is affected by high cellular levels of IF1. However, P2, but not P1, increases in activity as a function of the growth rate of the cell and is the dominant promoter in rich medium. Therefore, metabolic control of infA expression occurs exclusively at the level of transcription by the P2 promoter. PMID- 1909329 TI - Translational control of ornithine aminotransferase. Modulation by initiation factor eIF-4E. AB - Ornithine aminotransferase (OAT) is a mitochondrial enzyme expressed at high levels in liver, kidney, and retina. To characterize OAT regulation in retinal lines, we have been studying OAT synthesis in retinoblastomas RB355 and Y79. Our previous data (Fagan, R.J., Sheffield, W.P., and Rozen, R. (1989) J. Biol. Chem. 264, 20513-20517) indicated similar OAT mRNA levels in the two strains with 3 fold greater immunoreactive OAT protein and enzyme activity in Y79. To examine the regulatory mechanisms in these cell lines, we performed nuclear runoff experiments and characterized polysome-associated OAT mRNAs. The nuclear runoff data did not reveal any differences in transcription between the two strains. However, OAT mRNA of the RB355 strain was present in the lighter polysome fractions as compared with Y79. Treatment with cycloheximide, which slows the rate of elongation, indicated that initiation was decreased in RB355. Eukaryotic initiation factor eIF-4E mRNA and protein were reduced in RB355, suggesting that eIF-4E might be rate-limiting for OAT translation. Overexpression of a wild-type eIF-4E in RB355 shifted the OAT mRNA into denser fractions of the gradient and increased the amount of OAT protein to the level observed in Y79; overexpression of a mutant eIF-4E had no such effect. We previously identified an alternatively spliced OAT mRNA (containing exon 2) in these cells. This mRNA appeared in the lightest fractions of the gradient in both strains and was not affected by eIF-4E overexpression. PMID- 1909330 TI - Resistance to killing by tumor necrosis factor in an adipocyte cell line caused by a defect in arachidonic acid biosynthesis. AB - We have found that TA1-R6, which are resistant to the cytotoxic effects of tumor necrosis factor (TNF) in the presence of cycloheximide (Reid, T. R., Torti, F., and Ringold, G. M. (1989) J. Biol. Chem. 264, 4583-4589), have reduced ability to release arachidonic acid (20:4) from membrane phospholipids in response to either TNF or the calcium ionophore A23187 treatment. However, no defect in the activity of phospholipase A2, the principal enzyme responsible for the release of 20:4 from phospholipids, was observed in these cells. Detailed biochemical characterization of these TNF-resistant cells has revealed that these cells are unable to synthesize 20:4 endogenously because of a defect in delta 6-desaturase, the rate-limiting enzyme of 20:4 biosynthesis. This deficiency leads to a marked decrease in the steady-state levels of 20:4 present in choline-containing phospholipid (PC) and ethanolamine-containing phospholipid (PE). The TA1-R6 cells, however, are capable of incorporating exogenous 20:4 into PC and PE, and when loaded in such manner they become significantly more sensitive to the cytotoxic effects of TNF in the presence of cycloheximide. Therefore, the release of arachidonic acid from phospholipids appears to be a critical element in the signaling pathway utilized by TNF and is essential to the rapid cytotoxic response elicited by TNF in the absence of protein synthesis in wild-type TA1 cells. PMID- 1909331 TI - Interactions of plasminogen and tissue plasminogen activator (t-PA) with amphoterin. Enhancement of t-PA-catalyzed plasminogen activation by amphoterin. AB - The heparin-binding p30 protein amphoterin is proposed to mediate adhesive interactions of the advancing plasma membrane in migrating and differentiating cells. Since the NH2-terminal part of amphoterin is exceptionally rich in lysine residues, we have studied its interactions with plasminogen and tissue plasminogen activator (t-PA). On immunostaining of N18 neuroblastoma cells, amphoterin and t-PA showed a close co-localization in the filopodia of the leading membrane and in the substrate-attached material. In purified systems, both t-PA and plasminogen bound to immobilized amphoterin, and their binding was inhibited by the lysine analogue epsilon-aminocaproic acid. Plasminogen bound to immobilized amphoterin was activated by t-PA, and this resulted in effective degradation of the immobilized amphoterin. Correspondingly, amphoterin-bound t-PA activated plasminogen. In solution amphoterin accelerated t-PA-catalyzed plasminogen activation maximally 46-fold. The results indicate that t-PA and plasminogen form through their lysine-binding sites a complex with amphoterin, which results in acceleration of plasminogen activation and effective degradation of amphoterin. We suggest that local acceleration of t-PA-catalyzed plasminogen activation by amphoterin at the leading membrane enhances the penetration of growing cytoplasmic processes through extracellular materials during cell migration, differentiation and regeneration. The amphoterin-mediated adhesion at the leading membrane may be transient in nature, because the protein also enhances its own breakdown by accelerating t-PA-catalyzed plasminogen activation. PMID- 1909332 TI - Secretion of the beta/A4 amyloid precursor protein. Identification of a cleavage site in cultured mammalian cells. AB - Alzheimer's disease, a progressive neurodegenerative disorder, affects greater than 10% of the population of individuals greater than 65 years of age. A principal neuropathological feature of this disease is the senile plaque, a fibrillar extracellular deposit primarily composed of a approximately 4-kDa peptide, beta/A4, derived from the amyloid precursor protein (APP). Studies in cultured cells have documented that APP matures through a constitutive secretory pathway and is cleaved at or near the cell surface to release a large ectodomain into the extracellular space. To define the APP cleavage site, we constructed a Chinese hamster ovary cell line, which constitutively overexpresses human APP 770, and analyzed the COOH termini of secreted APP-770-related molecules. Using plasma desorption mass spectrometry and chemical microsequencing, we document that an APP cleavage site in Chinese hamster ovary cells leading to secretion occurs immediately COOH-terminal to lysine residue 687, which lies adjacent to the hydrophobic membrane-spanning domain. PMID- 1909333 TI - Solutions to diarrhea. PMID- 1909334 TI - From genes to tensile forces: genetic dissection of contractile protein assembly and function in Drosophila melanogaster. AB - Myofibrils, the contractile organelles of skeletal muscle, are highly ordered and precisely regulated actomyosin networks. Investigations of myofibril assembly are revealing the cellular mechanisms by which contractile components are arranged and regulated. In order to facilitate this research we have developed formal molecular genetics for myofibrillar proteins of Drosophila flight muscle. Presently, mutations can be used systematically to perturb or eliminate any of the classical myofibrillar proteins within these fibers, and the in vivo consequences can be conveniently evaluated using protein electrophoresis, electron microscopy, or by assaying flight performance. Here we review some recent progress. PMID- 1909335 TI - Protein engineering and the study of muscle contraction in Drosophila flight muscles. AB - We describe an experimental approach to the use of genetics to study muscle contraction in Drosophila melanogaster. Mutations induced by in vitro mutagenesis are inserted into the genome of flies using P-element mediated transformation, permitting the effects of the mutant genes to be studied in vivo in the indirect flight muscles (IFMs). Details of how mechanical experiments can be performed on skinned IFMs, despite their small size, are provided. The effects of two in vitro actin mutations, G368E and E316K, are described. The problems of performing biochemical and biophysical experiments on the IFMs and their myofibrillar proteins are described, together with indications as to how these may be overcome. PMID- 1909336 TI - Effects of beta-xylosides on proteoglycan biosynthesis and morphology of PC12 pheochromocytoma cells and primary cultures of rat cerebellum. AB - We have examined the effects of beta-xylosides, which act as exogenous acceptors for glycosaminoglycan chain initiation, on the morphology and proteoglycan biosynthesis of PC12 pheochromocytoma cells, and on monolayer, aggregate and explant cultures of early postnatal rat cerebellum. PC12 cells cultured for 13 days in the presence of nerve growth factor (NGF) and beta-xyloside, and labeled during days 11-13 with sodium [35S]sulfate, showed an 8- to 11-fold increase in [35S]sulfate-labeled macromolecules released into the culture medium. Most of the increase was accounted for by chondroitin sulfate, which was in the form of free glycosaminoglycan chains, which were not acid-precipitable. The presence of beta xyloside also led to a 65-115% increase in [35S]sulfate incorporation into cell associated glycosaminoglycans and glycoproteins of untreated and NGF-treated PC12 cells, respectively. beta-Xyloside treatment reduced the size of the chondroitin sulfate chains in both the cells and medium from approximately 34,000 to 10,000 Mr, but had much less effect on heparan sulfate, which decreased in size from 16,000 to 13,000-14,500 Mr (in the medium and cells, respectively). beta-Xyloside inhibition of proteoglycan biosynthesis was accompanied by significant morphological effects in NGF-treated PC12 cells, consisting of an increase in length and decrease in the branching, diameter and adhesion to the collagen substratum of the PC12 cell processes. p-Nitrophenyl- and 4-methylumbelliferyl beta-D-xylosides produced similar effects, which were not seen with p-nitrophenyl beta-D-galactoside. beta-Xylosides also produced distinct alterations in the adhesion and morphology of monolayer, aggregate, and explant cultures of early postnatal rat cerebellum, which occurred together with inhibition of chondroitin sulfate proteoglycan biosynthesis and a decrease in glycosaminoglycan chain size. These studies indicate that chondroitin sulfate (and probably also heparan sulfate) proteoglycans play a significant role in modulating cell-cell and cell matrix interactions in nervous tissue development and differentiation. PMID- 1909337 TI - Cytoskeletal rearrangements accompanying salmonella entry into epithelial cells. AB - Salmonella bacteria can enter (invade) eukaryotic cells, and exist as intracellular parasites. Confocal, light immunofluorescence and electron microscopy were used to examine various cytoskeletal components of cultured Madin Darby canine kidney (MDCK) and HeLa epithelial cells after infection with Salmonella typhimurium. These bacteria entered and remained within membrane-bound vacuoles and were surrounded by large (5-10 microns) dense structures composed of various cytoskeletal components. These structures consisted of extensive aggregations of polymerized actin, alpha-actinin and tropomyosin above and beside the invading bacterium in both epithelial cell lines. These structures were evident soon after bacterial addition (maximal at 20 min for HeLa cells, 60 min for MDCK cells), and disappeared later in the infection as the cytoskeletal components returned to a more normal distribution after bacterial internalization. Surprisingly, tubulin also aggregated above internalized Salmonella although bacterial entry or penetration through polarized monolayers was not disrupted by the microtubule-inhibiting agent nocadazole (this treatment actually enhanced tubulin accumulation around these organisms). There were little if any rearrangements in intermediate filaments composed of keratin or vimentin. Large amounts of talin also accumulated above and around invading Salmonella, but there was only a minor accumulation of vinculin around a few organisms. Pretreatment of epithelial cells with the microfilament inhibitor cytochalasin D blocked bacterial internalization but did not prevent accumulation of polymerized actin and alpha-actinin directly beneath uninternalized bacteria, yet prevented accumulation of the other cytoskeletal components. These results suggest that Salmonella bind to the surface and trigger a signal in epithelial cells that causes marked rearrangements in various cytoskeletal components, including recruitment of actin filaments and alpha-actinin, which then generates the force necessary for bacterial uptake. PMID- 1909338 TI - Effects of truncated neurofilament proteins on the endogenous intermediate filaments in transfected fibroblasts. AB - The expression and assembly characteristics of carboxyl- and amino-terminal deletion mutants of rat neurofilament low Mr (NF-L) and neurofilament middle Mr (NF-M) proteins were examined by transient transfection of cultured fibroblasts. Deletion of the carboxyl-terminal tail domain of either protein indicated that this region was not absolutely essential for co-assembly into the endogenous vimentin cytoskeleton. However, deletion into the alpha-helical rod domain resulted in an inability of the mutant proteins to co-assemble with vimentin into filamentous structures. Instead, the mutant proteins appeared to be assembled into unusual tubular-vesicular structures. Additionally, these latter deletions appeared to act as dominant negative mutants which induced the collapse of the endogenous vimentin cytoskeleton as well as the constitutively expressed NF-H and NF-M cytoskeletons in stably transfected cell lines. Thus, an intact alpha helical rod domain was essential for normal IF co-assembly whereas carboxyl terminal deletions into this region resulted in dramatic alterations of the existing type III and IV intermediate filament cytoskeletons in vivo. Deletions from the amino-terminal end into the alpha-helical rod region gave different results. With these deletions, the transfected protein was not co-assembled into filaments and the endogenous vimentin IF network was not disrupted, indicating that these deletion mutants are recessive. The dominant negative mutants may provide a novel approach to studying intermediate filament function within living cells. PMID- 1909339 TI - Application of an anhydrotrypsin-immobilized precolumn for selective separation of peptides having arginine or lysine at their C-termini by column-switching high performance liquid chromatography. AB - A column-switching high-performance liquid chromatographic (CS-HPLC) system which consisted of an anhydrotrypsin (AHT)-immobilized diol-silica precolumn and a reversed-phase analytical column was developed for the selective separation of peptides having Arg or Lys at their C-termini. Tuftsin (Thr-Lys-Pro-Arg) could be enriched almost quantitatively on the precolumn when loaded with water as a carrier solvent and the precolumn was washed with 10-30 mM acetate buffer (pH 5.0). An investigation of the affinity characteristics of 55 peptides to the AHT precolumn showed that among twelve peptides having Arg or ArgNH2 at their C termini and more than four amino acid residues, ten were retained almost quantitatively on the precolumn, and eight out of nine peptides having Lys at their C-termini were less retained. The peptide having D-Arg at its C-termini was not retained. However, twelve out of thirty peptides having no Arg or Lys at their C-termini were also retained, but the retention was greatly decreased, in contrast to the Arg peptides, when the precolumn was washed with 20 mM calcium chloride solution. The results indicate that the CS-HPLC system equipped with an AHT precolumn offers new selectivity in the HPLC selectivity in the HPLC separation of peptides. PMID- 1909340 TI - Problems associated with interferences in the analysis of serum for polychlorinated biphenyls. AB - During a recent survey to determine serum concentrations of polychlorinated biphenyls (PCBs) among people living around New Bedford, MA, U.S.A., an unidentified contaminant precluded the quantification of some early eluting Webb and McCall peaks. Loss of data is estimated to have reduced reported serum levels by 12%. Efforts to identify the contaminant by gas chromatography with an electron-capture detector, a Hall electrolytic condutivity detector, and mass spectrometer were not successful. Researchers ascertained, however, that the contaminant is not a PCB, it does not contain halogens, but it may contain phthalates. Vacutainer tubes and closures for serum storage bottles are suspected sources of contamination. PMID- 1909341 TI - Stereospecific high-performance liquid chromatographic determination of tocainide. AB - A sensitive high-performance liquid chromatographic assay was developed for the determination of tocainide enantiomers in plasma. Following extraction of tocainide from plasma, the enantiomers were derivatized with S-(+)-1-(1 naphthyl)ethylisocyanate. The resulting diastereomers were separated and quantified using normal-phase chromatography with fluorescence detection set at 220/345 nm (excitation/emission). The peaks, resolved with a resolution factor greater than 1.5, were free from interference. Linearity was established over the concentration range 0.25-10.0 mg/l for each enantiomer in plasma (r2 greater than 0.998). The inter-assay variability was less than 10% at all concentrations examined. The method can be used to determine the pharmacokinetics of tocainide enantiomers in man. PMID- 1909342 TI - High-performance liquid chromatography followed by radioimmunoassay for the determination of a luteinizing hormone-releasing hormone analogue, leuprorelin, and its metabolite. AB - A sensitive method for the determination of leuprorelin (TAP-144), a luteinizing hormone-releasing hormone analogue, and its C-terminal metabolite, M-I, in serum and urine has been developed. Leuprorelin and M-I were extracted from serum or urine samples with Sep-Pak C18 cartridges, and separated completely by high performance liquid chromatography and determined by radioimmunoassay using [125I]leuprorelin as the labelled antigen. The detection limit of the method was 0.05 ng/ml for leuprorelin and M-I, and the recovery of the compounds added to serum and urine was over 88% with a coefficient of variation (within-assay) of less than 5%. The method was applied to the determination of leuprorelin and M-I like immunoreactivity in serum or urine after administration of once-a-month injectable microspheres of leuprorelin acetate (TAP-144-SR) to patients with prostate cancer. PMID- 1909343 TI - Cross-reactivity and antigenic heterogeneity among Actinobacillus pleuropneumoniae strains of serotypes 4 and 7. AB - Actinobacillus pleuropneumoniae strains of serotypes 4 and 7 were studied for their antigenic properties by means of agglutination, coagglutination, indirect hemagglutination, immunodiffusion, and counterimmunoelectrophoresis tests. Strains of serotype 4 showed cross-reactivity with those of serotype 7 in various serological tests. Serotype 7 strains were antigenically heterogeneous and shared common antigens with several other serotypes. By using boiled whole-cell saline extract as the antigen in the immunodiffusion test, serotype 7 strains could be divided into four subgroups. Subgroup I strains did not have antigens in common with other serotypes, whereas subgroup II strains had antigens in common with serotype 4; subgroup III strains had antigens in common with serotype 10, and subgroup IV had antigens in common with serotypes 1, 9, and 11. The indirect hemagglutination test using unheated whole-cell saline extract as the antigen detected serotype-specific activity. Quantification of serotype-specific and group-specific antigens by coagglutination and immunodiffusion tests was found useful for identifying strains that belonged to serotype 4 or 7. PMID- 1909344 TI - Enzyme-linked immunosorbent assay using monoclonal antibodies for identification of mycobacteria from early cultures. AB - A simple enzyme-linked immunosorbent assay (ELISA) for the identification of cultured mycobacteria belonging to the Mycobacterium tuberculosis complex, the Mycobacterium avium complex, and Mycobacterium kansasii has been developed (R. Schoningh, C. P. H. J. Verstijnen, S. Kuijper, and A. H. J. Kolk. J. Clin. Microbiol. 28:708-713, 1990). The test for the routine identification of cultured mycobacteria was introduced in five clinical laboratories located in Tanzania, Thailand, Vietnam, and The Netherlands. The ELISA can be conducted without an ELISA reader since the test can be read visually. The results of identification of 255 strains of the M. tuberculosis complex by microbiological means and by ELISA were compared; the specificity and the sensitivity were 100%. For the M. avium complex, the specificity was 100% and the sensitivity was 64%. All 26 M. kansasii strains tested could be identified as M. kansasii. The ELISA described here proved to be useful in both well- and modestly equipped laboratories and may replace the microbiological method of identification of M. tuberculosis and M. kansasii. PMID- 1909345 TI - Comparisons of standard curve-fitting methods to quantitate Neisseria meningitidis group A polysaccharide antibody levels by enzyme-linked immunosorbent assay. AB - We examined several of the more commonly used models (log-log, two forms of the logit-log, and the four-parameter logistic-log transformations) for forming standard or calibration curves by using a standardized enzyme-linked immunosorbent assay (ELISA). Assay range, accuracy, and error for each function were measured and compared. Antibody levels to Neisseria meningitidis group A polysaccharide were estimated by calculating antibody concentrations of a serially diluted standard reference serum of known concentration. Each function achieved a high squared correlation coefficient (r2 greater than 0.97), indicating a high degree of accuracy in forming the standard curves. However, when predicted antibody concentrations were compared with the known values, the log-log function exhibited the least precision, with extreme percentages of error occurring at several dilutions. A partially specified logit-log transformation performed better than the log-log model over a reduced range of standard dilutions. This indicated that a high r2 alone was not a reliable measure of the accuracy of the standard curve. Of the methods surveyed, the logistic-log and fully specified logit-log functions were the most accurate models for forming standard curves and for interpolating antibody concentrations from the standard curve. The accuracy of the fully specified logit-log function is highly dependent on the precise specification of two unknown quantities, the optical densities at zero and infinite concentrations, prior to fitting the model to a typical set of calibration data. The four-parameter logistic-log function was the preferred choice for quantitating N. meningitidis group A total polysaccharide antibody by using a standardized ELISA. The function does not require prespecification of any parameters before estimating the standard curve, and the four parameters are readily interpretable in terms of identifiable physical quantities. This model also has the advantage that it is easiest to visualize since it does not incorporate complex transformations of the optical density scale. PMID- 1909346 TI - Production of polyclonal and monoclonal antibodies against group A, B, and C capsular polysaccharides of Neisseria meningitidis and preparation of latex reagents. AB - Polyclonal and monoclonal antibodies against capsular polysaccharides of Neisseria meningitidis serogroups A, B, and C were produced in order to develop immunological reagents allowing both the detection of soluble antigens during meningococcal meningitis and antigenic serogrouping of N. meningitidis cultures. The performance characteristics of monoclonal and polyclonal antibody latex reagents were compared. For the detection of soluble polysaccharide antigen, polyclonal antibody latex reagent was selected for N. meningitidis A and C. The latex reagent prepared with polyclonal antibodies against N. meningitidis B could not detect capsular polysaccharide even at 1 mg/ml. The monoclonal antibody B latex reagent which detected 100 ng of polysaccharide per ml was therefore chosen. For the serogroup identification of N. meningitidis, the use of a confirmatory test results in an overall specificity of 100% with polyclonal or monoclonal antibody latex reagents. PMID- 1909347 TI - Characterization of serogroup A and B strains of Neisseria meningitidis with serotype 4 and 21 monoclonal antibodies and by multilocus enzyme electrophoresis. AB - The reactions of serogroup A strains of Neisseria meningitidis with one monoclonal antibody specific for serotype 21 and three different monoclonal antibodies specific for serotype 4 were compared with those of serogroup B strains previously assigned to serotype 4. Antibody binding was studied by enzyme linked immunosorbent assay (ELISA), dot blotting, and immunoblotting. Characterization of the isolates by the electrophoretic mobilities of 14 metabolic enzymes showed 50 multilocus enzyme genotypes. All except two genotypes fell into three distinct clusters: I, IIa and IIb. The enzyme genotypes of serogroup B strains were mainly in cluster I, and 88% of the serogroup A strains had genotypes in clusters IIa and IIb. Serogroup B strains generally reacted with all three serotype 4 monoclonal antibodies in ELISA and dot blotting but with only two in immunoblots. Serogroup A strains showed two different reactions in the blotting methods: either binding of the serotype 21 antibody only or binding of this and two of the three serotype 4 monoclonal antibodies. Strains of the first pattern were in clusters I and IIa, whereas all but two strains in cluster IIb were of the second pattern. In ELISA, an additional reaction of two of the serotype 4 monoclonal antibodies with serogroup A isolates was observed. The different binding of these two monoclonal antibodies in ELISA and the blotting methods appeared to result from heat inactivation of the meningococcal cells and use of detergent-containing reagents in ELISA. The results show that the serotype of serogroup A strains is distinct from serotype 4 of serogroup B strains. PMID- 1909348 TI - Differentiation of Bacillus anthracis from Bacillus cereus by gas chromatographic whole-cell fatty acid analysis. AB - Three strains of Bacillus anthracis and seven strains of Bacillus cereus were grown on complex medium and on synthetic medium. Gas chromatographic analysis of whole-cell fatty acids of strains grown on complex medium gave nearly identical fatty acid patterns. Fatty acid patterns of strains grown on synthetic medium showed a high content of branched-chain fatty acids. Significant differences between the fatty acid patterns of the two species were found. Odd iso/anteiso fatty acid ratios were about equal in B. anthracis strains, whereas in B. cereus strains the fractions of iso acids were at least twice as high as the fractions of anteiso acids. The method described herein is used in our diagnostic laboratory to help differentiate between these two species. PMID- 1909349 TI - Perestroika and health care in the USSR: innovations in state financing. AB - The budget of the USSR Ministry of Health has steadily been shrinking during the period 1960-1985 as a proportion of the standard measure of national productivity. In the age of perestroika, however, the Ministry of Health and various units within it have instituted a number of innovative attempts to increase available funds and resources on one hand, and make facilities operate more efficiently on the other. Some of these strategies include the expansion of pay polyclinics and hospitals, the institution of self-financing and cost accounting procedures, the initiation of health insurance forms of reimbursement, more control over the budget at lower levels, and the geographical reorganization of health care facilities. There are concerns about the effectiveness of these innovations, and the issue of quality of care. It is not clear which if any of these innovations will achieve the desired goals. PMID- 1909350 TI - Role of T lymphocyte subsets in the pathogenesis of primary infection and rechallenge with respiratory syncytial virus in mice. AB - The role of CD4+ and CD8+ T lymphocytes in terminating respiratory syncytial virus (RSV) replication, causing disease, and protecting from reinfection was investigated using a BALB/c mouse model in which CD4+ or CD8+ lymphocytes or both were depleted by injections of Mab directed against the respective mouse lymphocyte determinants. Kinetics of RSV replication, illness, and pathology were assessed after primary infection and rechallenge. Both CD4+ and CD8+ lymphocyte subsets were involved in terminating RSV replication after primary infection. When both T lymphocyte subsets were depleted RSV replication was markedly prolonged, yet no illness was evident, suggesting that host immune response rather than viral cytocidal effect was the primary determinant of disease in mice. Both CD4+ and CD8+ lymphocytes contributed to illness, although CD8+ lymphocytes appeared to play the dominant role in this particular system. Analysis of histological responses suggested that CD4+ lymphocytes were required for the appearance of peribronchovascular lymphocytic aggregates seen in normal mice after rechallenge, and that the presence of alveolar lymphocytes was correlated with illness. It is postulated that antibody is an illness-sparing mechanism for protecting mice from RSV infection, and that T lymphocytes are an important determinant of illness. Further delineation of RSV-induced immunopathogenesis in primary infection and reinfection will provide important information for the development of vaccine strategies. PMID- 1909351 TI - Heterogeneity of plasma von Willebrand factor multimers resulting from proteolysis of the constituent subunit. AB - In this report we demonstrate that proteolytic cleavage of the constituent subunit is one of the causes determining the heterogeneous size distribution of plasma von Willebrand factor (vWf) multimers. As shown by two-dimensional nonreduced/reduced agarose/polyacrylamide gel electrophoresis, the structure of circulating vWf molecules may deviate from that represented by assemblage of a variable number of identical subunits. Indeed, even though the largest multimers in normal plasma appear to be composed predominantly of intact 225-kD subunits, those of intermediate and smaller size contain also 189-, 176-, and 140-kD proteolytic fragments. Different subunit composition patterns are repeated regularly in multimers of increasing molecular mass, yielding series of bands with similar structure. One of these series consists of molecules without evidence of proteolytic fragmentation, and its smallest member appears to be a dimer of 225-kD subunits. Type IIA von Willebrand disease, characterized by absence of the largest multimers, displays a pattern wherein the fragments of 176 and 140 kD are relatively increased, that of 189 kD is markedly decreased or absent, but the composition of individual multimers is otherwise similar to that of species seen also in normal plasma. In contrast to those in the circulation, all normal platelet vWf multimers contain only intact subunit. These results suggest that proteolytic cleavage of plasma vWf subunits occurs after release from cellular sites, whereas platelet vWf stored in alpha-granules is protected from proteolysis. These findings provide information that may be relevant for understanding the normal processing of vWf multimers and for elucidating the pathogenesis of some of the congenital and acquired structural abnormalities of this molecule. PMID- 1909353 TI - Variable region diversity in human circulating antibodies specific for the capsular polysaccharide of Haemophilus influenzae type b. Preferential usage of two types of VH3 heavy chains. AB - Antibodies against capsular polysaccharides are important in the defense against many pathogenic bacteria. To determine the mechanism for the variability in responses to polysaccharides, a panel of well characterized serologic reagents that identify diagnostic primary amino acid sequences in the framework and hypervariable regions of heavy (H) and light (L) chains were created to characterize the variable region diversity in circulating human antibodies. 10 normal adult volunteers were immunized with the type b capsular polysaccharide of Haemophilus influenzae (Hib PS). By immunoblot analyses each individual was found to use at least three different variable L (VL) families, but all had preferential usage of VH3-derived H chains. Four individuals had lesser populations of VH1-derived H chains and three had populations of VH4-derived H chains, but anti-Hib PS antibodies derived from the VH2, VH5, and VH6 families were not detected. The anti-Hib PS antibodies from all subjects were also identified by serologic markers for two specific types of VH3 H chains. These H chains are structurally related to the 20P1 and 30P1 VH genes that are preferentially rearranged in the early human repertoire. These findings document the VH restriction of physiologic responses to Hib PS immunization, and demonstrate a technique to directly assess the structural and genetic diversity of specific serum antibodies. PMID- 1909354 TI - Trends in elderly hospitalization and readmission rates for a geographically defined population: pre- and post-prospective payment. AB - To address the paucity of patient-level data regarding the effectiveness of Medicare's prospective payment system (PPS), we conducted a population-based study of inpatient hospitalizations among individually identified elderly residents of Olmsted County, Minnesota, 1970-1987. A 4.3% increase in total days of care/1000 population from 2,652/1,000 in 1970 to 2,766/1,000 in 1980 was followed by a 9.8% decline from 1980 to 1987 (2,495/1,000). The decline was due primarily to a 13.4% decrease in mean length stay (9.7 days in 1980 to 8.4 days in 1987). The number of hospitalizations/1,000 Olmsted County elderly in 1980 was already below 1987 U.S. figures and did not exhibit the decline evidenced nationally between 1980 and 1987. A 4.6% decline in the proportion of county residents age 65-74 years who were hospitalized (174/1,000 in 1980 to 166/1,000 in 1987) was offset by an 8.3% increase for persons age greater than or equal to 75 (252/1,000 to 273/1,000) and by a 5.7% increase in the number of hospitalizations per individual hospitalized for persons age 65-74 years (1.34 to 1.42). Using a time-dependent Cox model, which adjusted for differences in patients characteristics between years, there was a significantly higher risk of readmission within 14 days in 1987 vs 1980 (hazard ratio (HR) = 1.33, 95% confidence interval (CI) = 1.05-1.70). The difference between years was no longer evident at 30 or 60 days (HR = 0.84, 95% CI = 0.63-1.11 between 15 and 30 days; HR = 1.12, 95% CI = 0.84-1.49 between 31 and 60 days). This study suggests that initial effects of PPS on utilization may be temporary and that more research is needed to appreciate the impact of cost-containment on patient outcome. PMID- 1909355 TI - Pathological effects of Blastocrithidia triatomae (Trypanosomatidae) on the reduviid bug Triatoma infestans after infection by membrane feeding and long-term starvation. AB - Developmental time and mortality in larvae of the reduviid bug Triatoma infestans were studied in uninfected groups and in those infected with Blastocrithidia triatomnae by in vitro feeding with 10(4) cyst stages/cm(3) blood. Bugs were subsequently subjected to two different starvation periods. In bugs fed at weekly intervals infection with B. triatomae was associated with developmental retardation, increasing in the final instars, and with increased mortality in the third and preadult instar. Compared to these groups, long-term starvation caused slightly lower mortality rates of uninfected groups and in infected bugs a remarkably higher mortality rate in the preadult instar. Total mortality rates of infected groups were nearly unaffected by starvation. PMID- 1909352 TI - Differential effects of insulin deficiency on albumin and fibrinogen synthesis in humans. AB - Insulin deficiency decreases tissue protein synthesis, albumin mRNA concentration, and albumin synthesis in rats. In contrast, insulin deficiency does not change, or, paradoxically, increases estimates of whole body protein synthesis in humans. To determine if such estimates of whole body protein synthesis could obscure potential differential effects of insulin on the synthetic rates of individual proteins, we determined whole body protein synthesis and albumin and fibrinogen fractional synthetic rates using 5-h simultaneous infusions of [14C]leucine and [13C]bicarbonate, in six type 1 diabetics during a continuous i.v. insulin infusion (to maintain euglycemia) and after short-term insulin withdrawal (12 +/- 2 h). Insulin withdrawal increased (P less than 0.03) whole body proteolysis by approximately 35% and leucine oxidation by approximately 100%, but did not change 13CO2 recovery from NaH13CO3 or estimates of whole body protein synthesis (P = 0.21). Insulin deficiency was associated with a 29% decrease (P less than 0.03) in the albumin fractional synthetic rate but a 50% increase (P less than 0.03) in that of fibrinogen. These data provide strong evidence that albumin synthesis in humans is an insulin sensitive process, a conclusion consistent with observations in rats. The increase in fibrinogen synthesis during insulin deficiency most likely reflects an acute phase protein response due to metabolic stress. These data suggest that the absence of changes in whole body protein synthesis after insulin withdrawal is the result of the summation of differential effects of insulin deficiency on the synthesis of specific body proteins. PMID- 1909356 TI - Parasitism of newly-hatched Aedes sierrensis (Diptera: Culicidae) larvae by Lambornella clarki (Ciliophora: Tetrahymenidae) following habitat flooding. AB - Host-parasite interactions between Lambornella clarki (Ciliophora: Tetrahymenidae) and its natural host, Aedes sierrensis (Diptera: Culicidae), were studied in newly flooded treeholes in northern California between 1986 and 1989. First instar host larvae hatched within 1 to 4 hr of flooding, while free-living trophonts of L. clarki appeared between 7 and 24 hr. As early as 24 hr after flooding, ciliates initiated the first parasite cycle by forming cuticular cysts on first instar larvae; by 64 hr, cysts were observed on larvae collected from all positive holes during all years. While larvae with as many as 12 cysts were observed, most supported only 1 cyst, and successful infections were established by the entry of a single ciliate into the host's hemocoel. Among treehole populations, the proportion of larvae with L. clarki cysts ranged from 2 to 100% at 48 hr indicating that enzootics and epizootics develop rapidly in newly flooded treeholes. Average attack rates from all holes by year ranged between 17.0 and 44.4%. Ciliates began entering hosts 48 to 72 hr after flooding, but some larvae escaped parasitization by molting to the second instar before ciliates penetrated the cuticle. In some treeholes, opportunistic microorganisms entered larvae with the invading ciliates and killed both the host and parasite. PMID- 1909357 TI - [Effects of hypergravity on migration, proliferation and function of mouse osteoblastic cell line MC3T3-E1]. AB - The purpose of this study was to investigate the hypergravity-induced responses and their mediators of osteoblastic cell line, MC3T3-E1. The synchronized G1 or the S Phase cells were exposed to 5 and 18 x g hypergravity at 37 degrees C. The migration velocity was measured and the morphology was observed. MC3T3-E1 cells were cultured for 1, 2 or 3 days at 37 degrees C, exposing to 5, 10, 20 and 40 x g hypergravity. The proliferation, prostaglandin E2 (PGE2) production rate and alkaline phosphatase (ALPase) activity were measured. The results were as follows: 1) In the G1 phase of the cell cycle, the migration of MC3T3-E1 cells was increased by 18 x g. In the S phase, the morphology altered depending on the g-stress. 2) The proliferation of MC3T3-E1 cells was enhanced at 20 and 40 x g but reduced at 10 x g. The proliferation of HeLa cells and JTC-12 cells was also enhanced at 40 x g. 3) Indomethacin (10(-5)M) reduced the proliferation of MC3T3 E1 cells induced by 40 x g. But indomethacin (10(-5)M) did not reduce the proliferation of HeLa cells. 4) The increase of the released PGE2 from the cells depended on the time (1-8h) and the gravity (1-40 x g). 5) The increase of the ALPase activity of MC3T3-E1 cells also depended on the gravity. These results suggest that the hypergravity enhanced the proliferation of MC3T3-E1 cells via PGE2-mediated mechanism. PMID- 1909359 TI - The distribution of transcripts of neurogenic genes in neurogenic mutants of Drosophila melanogaster. AB - The neurogenic genes of Drosophila melanogaster are required for correct separation of neural and epidermal progenitor cells during early embryogenesis. Results from genetic analyses indicate that the neurogenic genes are functionally related. We have studied the spatial distribution of RNA from the neurogenic genes D1, neu, and m4, m5, m7 and E(spl) [four genes of the Enhancer of split complex] in various neurogenic mutant embryos by in situ hybridization. An abnormal distribution of RNA from certain of the genes is found in neurogenic mutants, suggesting that at least some of the functional interactions inferred from genetic data take place at the transcriptional level. We discuss these results in relation to the events of early neurogenesis. PMID- 1909358 TI - Preservation of EDTA-expanded grid-mounted chromosomes and nuclei for electron microscopy using a specially designed freeze-dryer. AB - We describe methods for freezing and drying EDTA-expanded, fixed metaphase chromosomes and nuclei, attached to grids as whole-mounts, for transmission electron microscopy. These methods use a special apparatus that is simple to construct. While separate freezers and dryers are commercially available, one for freezing blocks of tissue by slamming them against a cold metal surface, and the other for vacuum drying the frozen tissue, our apparatus is designed for gentler, cryogenic liquid plunge freezing and drying, sequentially, in the same apparatus, thus avoiding any compression or damage to the specimen. Use of a cryoprotectant is not essential; however, good results are obtained more often when 20% ethanol is used. Freezing is accomplished by rapid propulsion of the grid, with specimens attached, into slushy N2 (-210 degrees C) within the drying chamber; drying is automatic, by either sublimation under vacuum or by solvent substitution using absolute ethanol followed by acetone, which, in turn, is removed with a critical point dryer. The apparatus offers a means of drying chromosomes and nuclei in an expanded state, and avoids the shrinkage of these structures that occurs during stepwise passage through increasing concentrations of ethanol or acetone. PMID- 1909360 TI - The release of factor VIII and tissue plasminogen activator can not be blocked by specific antagonists to vasopressin. AB - Vasopressin and in particular 1-deamino-8-D-arginine vasopressin (DDAVP) can release factor VIII (FVIII) and tissue plasminogen activator (tPA) to the blood. In the present study DDAVP was injected in conscious dogs which had been preloaded with specific antagonists either against vasopressin's vasopressor response (V1-receptors) or its antidiuretic response (V2-receptors). The presence in the blood of either of the antagonists had no effect on the increase of FVIII or tPA following stimulation with DDAVP. It is therefore concluded that the effect of DDAVP on coagulation and fibrinolysis is elicited via a new class of receptors different from the known V1- and V2-receptors. PMID- 1909361 TI - On the origins and present state of the art of G protein research. AB - G proteins are central to the transduction of many receptor signals. I review the "firsts" that have led to our current knowledge and pose some of the questions presently investigated in several laboratories around the world. PMID- 1909363 TI - Gonadotrophins and sex steroids during pregnancy and natural superfoetation in captive brown hares (Lepus europaeus). AB - In brown hares, which are induced ovulators, sexual behaviour occurs episodically at the beginning of pregnancy. From Day 34 (length of pregnancy is 41 days), the frequency of sexual chases followed by mating, ovulation and fertilization increased and 59% of pregnant females presented a natural superfoetation. The pattern of circulating luteinizing hormone (LH), follicle-stimulating hormone (FSH), oestradiol and progesterone was studied in 13 pregnant females left permanently with a male, and in 10 females isolated from males around Day 20 of pregnancy. In the 2 groups FSH concentrations were high at the beginning and end of pregnancy. All females presented a peak value of FSH in the last 4 days of pregnancy, regardless of mating stimuli. This peak value was higher for females left permanently with a male than for isolated ones. Oestradiol concentrations fluctuated between 20 and 100 pg/ml, without any clear correlation with sexual behaviour, stage of pregnancy or profiles of other hormones. Prepartum matings occurred when progesterone values were still greater than 50 ng/ml; they were followed by a transient rise in LH and by a periovulatory progesterone secretion, with values above 100 ng/ml in the morning after mating. Such modifications of LH and progesterone were not detected before Day 34, suggesting that mating stimuli are not able to induce an LH surge at the beginning of pregnancy. After Day 34, mating can induce an LH surge, ovulation and superfoetation. PMID- 1909362 TI - Urea gradient/SDS-PAGE; a useful tool in the investigation of signal transducing G proteins. AB - We describe an updated and improved protocol to perform urea gradient/SDS-PAGE in which proteins are electrophoresed through 9% polyacrylamide gel slabs in the presence of a linear 4 M to 8 M gradient of urea using Laemmli's separation buffers. We provide examples of this technique to separate PTX labeled G protein alpha subunits, as well as unlabeled alpha and beta subunits of G proteins. Applications of the technique are exemplified in which (1) the chromatographic separations of G proteins in DEAE-Toyopearl and MonoQ columns are compared, (2) the complexity of PTX substrates expressed in human erythrocytes, bovine brain, dog ventricle, FRTL-5 cells, HIT cells, GH4C1 cells and RIN cells are compared, and (3) the polypeptide composition of G protein beta gamma subunits, as expressed in several tissues and found in three distinct G proteins from a single cell population, are analyzed. PMID- 1909364 TI - Regulation of follicular development by diethylstilboestrol in ovaries of immature rats. AB - Immature female rats received either one injection of 2 mg diethylstilboestrol (DES)/rat subcutaneously and were killed 12 h later or received two injections of DES at 0 and 24 h and were killed at 24, 36 and 48 h after the initial injection. The ovarian follicles were released by enzymic digestion with collagenase and separated into those of small, medium and large diameter (less than 200 microns, 200-400 microns and greater than 400 microns) by filtration through graded Teflon sieves and granulosa cells were extracted from these follicles. The ovaries of immature rats treated with pregnant mares' serum gonadotrophin (PMSG) were used for comparative purposes. Incorporation of [3H]thymidine into granulosa cell DNA was augmented by DES and by PMSG. Small follicles were more strongly stimulated by DES at 12 h than those of other sizes, but rates increased significantly in medium and large follicles at 48 h. Aromatase activity in the DES-treated group was low at all times and in all follicles. Rates of oestrogen and progesterone production in response to 36 h of exposure to follicle-stimulating hormone (FSH) in vitro were significantly lower than in the PMSG-treated group. FSH-stimulated steroid production in the DES group at 36-48 h was lower, particularly in the medium follicles. A significant rise in serum FSH, luteinizing hormone (LH) and progesterone concentrations was noted only at 36 h after DES treatment, while serum and follicular fluid oestrogen values remained unchanged. When these changes were compared with those in PMSG-treated rats, there were obvious differences. The pattern of thymidine incorporation and aromatase activity differed with time and follicle size. Serum FSH and LH values were not affected by PMSG treatment, but serum and follicular fluid oestradiol values increased with time. The PMSG-treated animals ovulated in response to human chorionic gonadotrophin, but the DES-treated rats did not ovulate in spite of the presence of some large antral follicles in the ovaries. These findings show that initial exposure of follicles to high concentrations of oestrogen results in follicles which fail to respond to subsequent gonadotrophin surges and are thereby restricted in their ability to differentiate fully. PMID- 1909365 TI - Influence of temperature and gas atmosphere on in-vitro fertilization and embryo development in domestic cats. AB - The influence of culture temperature and gas atmosphere on in-vitro fertilization and embryo development was examined in the domestic cat. In Exp. 1, eggs were fertilized and cultured in 5% CO2 in air at 37, 38 or 39 degrees C. Experiment 2 evaluated the effects of 5% CO2 in air; 5% CO2, 5% O2 and 90% N2; and 10% CO2 in air. Fertilization (cleavage) and development to the morula/blastocyst stage were not influenced (P greater than 0.05) by variations in temperature and gas composition. Despite changing these culture conditions, egg cleavage averaged approximately 75% and greater than 80% of the 2-cell embryos proceeded to morulae in vitro. However, the partial in-vitro morula-to-blastocyst developmental block normally observed in this species was not removed. PMID- 1909366 TI - Regulation of gene expression and cellular localization of prostaglandin synthase by oestrogen and progesterone in the ovine uterus. AB - Expression of the gene for prostaglandin synthase (PGS) was examined in whole endometrial tissue derived from ewes during the oestrous cycle (Days 4-14), on Day 15 of pregnancy and following ovariectomy and treatment with ovarian steroid hormones. Whilst no significant differences were seen in PGS mRNA concentrations analysed by Northern blot analysis in endometrial tissue during the oestrous cycle or in early pregnancy, treatment of ovariectomized (OVX) ewes with oestradiol-17 beta markedly reduced endometrial PGS mRNA concentration. There was no difference in PGS mRNA concentration in ewes treated with progesterone, either alone or in conjunction with oestrogen, from that in OVX controls. In contrast, differences in immunolocalization of PGS observed in uterine tissue from OVX steroid-treated ewes were much more marked and reflected similar changes seen previously in the immunocytochemical distribution of endometrial PGS during the oestrous cycle. In OVX ewes and those treated with oestrogen, immunocytochemical staining for PGS was seen in stromal cells, but little immunoreactive PGS was located in the endometrial epithelial cells. However, in ewes treated with progesterone alone or with oestrogen plus progesterone, PGS was found in luminal and glandular epithelial cells and in stromal cells. Intensity of immunostaining for PGS in endothelial cells and myometrium did not differ between the treatments. Thus, whilst oestrogen lowers PGS mRNA in the endometrium, presumably in stroma, it may also increase the stability of the enzyme itself in the stromal cells. Although oestradiol-17 beta has no effect on PGS in endometrial epithelium, progesterone stimulates the production of PGS in endometrial epithelial cells without altering the overall abundance of PGS mRNA in the endometrium as a whole. Conceptus-induced changes in PGF-2 alpha release by ovine endometrium would not appear to be mediated via effects on PGS gene expression or protein synthesis. PMID- 1909367 TI - Morphine, naloxone and the gonadotrophin surge in ewes. AB - Possible endogenous opioid peptide regulation of the preovulatory gonadotrophin surge was examined in ewes during the breeding season. Intact ewes (n = 54) were synchronized by treatment for 12 days with intravaginal sponges releasing medroxyprogesterone acetate. Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion prior to and during the gonadotrophin surge were not affected by naloxone (0.33 mg/kg body wt per h) administered from the time of medroxyprogesterone acetate withdrawal until 30 h after the onset of oestrus (n = 6). Morphine was administered in 4 patterns: (i) 0.25 mg morphine/kg body wt per h from medroxy-progesterone acetate withdrawal until 30 h after the onset of oestrus (n = 6), (ii) 0.25 mg morphine/kg body wt per h from 24 to 48 h after medroxyprogesterone acetate withdrawal (n = 6), (iii) 0.50 mg morphine/kg body wt per h from 24 to 36 h after medroxyprogesterone acetate withdrawal (n = 6) and (iv) 0.50 mg morphine/kg body wt per h from 18 to 30 h after medroxyprogesterone acetate withdrawal (n = 6). Oestrus and the gonadotrophin surge were delayed, but not blocked, in all cases of morphine administration (P less than 0.05). Inconsistent effects of morphine on circulating oestradiol and gonadotrophin concentrations prior to the gonadotrophin surge suggest that the delays are not due to reduced gonadotrophic support of ovarian oestradiol output. Morphine may reduce responsiveness of central behavioural and gonadotrophin surge-generating centres to the oestradiol signal. The absence of effects of naloxone on gonadotrophin secretion suggest that suppression of LH secretion by opioid peptide activity is reduced after the end of the luteal phase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1909368 TI - Effects of human chorionic gonadotrophin on contractile activity of steroid primed pig myometrium in vitro. AB - We examined the effects of (a) oestrogen and progesterone on concentrations of luteinizing hormone/human chorionic gonadotrophin (LH/hCG) receptors in uterine smooth muscle in vivo and (b) hCG on spontaneous myometrial contractions in vitro. Ovariectomized gilts received 2 ml corn oil (control; n = 5), 2 mg oestradiol benzoate (n = 6) or 20 mg progesterone (n = 5) for 5 days. Gilts were hysterectomized 8 h after the last injection and longitudinal sections of myometrium were incubated in modified Krebs' solution with 0 or 10 i.u. of hCG (n = 10/gilt) for 4 h at 37 degrees C in 95% O2:5% CO2. After incubation, myometrial sections were placed in a tissue chamber perfused with Krebs' solution and mechanical activity was recorded for 30 min. Cell membrane fractions were prepared from myometrial tissue not used for in-vitro studies and analysed for LH/hCG receptors. Treatment with oestradiol benzoate increased (P less than 0.01) the number of LH/hCG-binding sites compared with gilts receiving corn oil or progesterone. Incubation of myometrium with hCG reduced (P less than 0.01) the frequency and amplitude of spontaneous uterine contractions in gilts treated with oestradiol benzoate. In contrast, hCG had no effect (P greater than 0.05) on the pattern of myometrial contractions in gilts given corn oil or progesterone. These results indicate that oestradiol promotes the synthesis of LH/hCG receptors in pig myometrium and incubation of oestrogen-primed tissue with hCG has a quiescent effect on myometrial contractility. PMID- 1909369 TI - Limbic epilepsy. PMID- 1909370 TI - Random walking. Creationism vs. Scientific American. PMID- 1909372 TI - NATO Advanced Research Workshop on Genome Structure and Evolution. Spetsai, Greece, 15-19 September 1990. Proceedings. PMID- 1909371 TI - Determinants of DNA sequence divergence between Escherichia coli and Salmonella typhimurium: codon usage, map position, and concerted evolution. AB - The nature and extent of DNA sequence divergence between homologous protein coding genes from Escherichia coli and Salmonella typhimurium have been examined. The degree of divergence varies greatly among genes at both synonymous (silent) and nonsynonymous sites. Much of the variation in silent substitution rates can be explained by natural selection on synonymous codon usage, varying in intensity with gene expression level. Silent substitution rates also vary significantly with chromosomal location, with genes near oriC having lower divergence. Certain genes have been examined in more detail. In particular, the duplicate genes encoding elongation factor Tu, tufA and tufB, from S. typhimurium have been compared to their E. coli homologues. As expected these very highly expressed genes have high codon usage bias and have diverged very little between the two species. Interestingly, these genes, which are widely spaced on the bacterial chromosome, also appear to be undergoing concerted evolution, i.e., there has been exchange between the loci subsequent to the divergence of the two species. PMID- 1909373 TI - Multigene families and the evolution of complexity. AB - Higher organisms are complex, and their developmental processes are controlled by the sequential expression of genes that often form multigene families. Facts are surveyed on how functional diversity of genes is related to duplication of genes or segments of genes, by emphasizing that diversity is often enhanced by alternate splicing and proteolytic cleavage involving duplicated genes or gene segments. Analyses of a population genetics model for the origin of gene families suggest that positive Darwinian selection is needed for acquiring gene families with desirable functions. Based on these considerations, examples that show acceleration of amino acid substitution relative to synonymous change during evolutionary processes are surveyed. Some of such examples strongly suggest that positive selection has worked. In other cases it is difficult to judge whether or not acceleration is caused by positive Darwinian selection. As a general pattern, acceleration of amino acid substitution is often found to be related to gene duplication. It is thought that complexity and diversity of gene function have been advantageous in the long evolutionary course of higher organisms. PMID- 1909374 TI - Elements in microbial evolution. AB - Spontaneous mutation, selection, and isolation are key elements in biological evolution. Molecular genetic approaches reveal a multitude of different mechanisms by which spontaneous mutants arise. Many of these mechanisms depend on enzymes, which often do not act fully at random on the DNA, although a large number of sites of action can be observed. Of particular interest in this respect are DNA rearrangement processes, e.g., by transposition and by site-specific recombination systems. The development of gene functions has thus to be seen as the result of both DNA rearrangement processes and sequence alterations brought about by nucleotide substitutions and small local deletions, insertions, and duplications. Prokaryotic microorganisms are particularly appropriate for studying the effects of spontaneous mutation and thus microbial evolution, as they have haploid genomes, so that genetic alterations become rapidly apparent phenotypically. In addition, bacteria and their viruses and plasmids have relatively small genomes and short generation times, which also facilitate research on evolutionary processes. Besides the strategy of development of gene functions in the vertical transmission of genomes from generation to generation, the acquisition of short DNA segments from other organisms appears to be an important strategy in microbial evolution. In this process of horizontal evolution natural vector DNA molecules are often involved. Because of acquisition barriers, the acquisition strategy works best for relatively small DNA segments, hence at the level of domains, single genes, or at most operons. Among the many enzymes and functional systems involved in vertical and horizontal microbial evolution, some may serve primarily for essential life functions in each individual and only secondarily contribute to evolution.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1909375 TI - On the mode of evolution of alpha satellite DNA in human populations. AB - The hypothesis that highly reiterated satellite DNAs in present-day populations evolve by molecular mechanisms that create, by saltatory amplification steps, new long arrays of satellite DNA, and that such long arrays are used for homogenization purposes, has been tested both in mouse and in humans. In mouse, the data obtained are consistent with this hypothesis. This was tested in more detail on chromosomes 13 and 21 of the human genome. A Centre d'Etudes du Polymorphisme Humain family, which in some individuals exhibits strong supplementary DNA bands following TaqI restriction endonuclease digestion and conventional gel electrophoresis, was analyzed by pulse field gel electrophoresis following restriction by BamHI. The supplementary bands on chromosome 13 (18 times the basic alpha satellite DNA repeat) and on chromosome 21 (a 9.5-mer) segregated with centromeric alpha satellite DNA blocks of 5 and 5.3 megabases, respectively. These are by far the largest alpha satellite block lengths seen in all chromosome 13 and chromosome 21 centromeric sequences so far analyzed in this manner. The possibility that these supplementary alpha satellite sequences were created in single individuals by saltatory amplification steps is discussed in light of our own data and that published by others. It is proposed that deletion events and unequal cross-overs, which both occur in large satellite DNA arrays, contribute to the homogenization of size and sequence of the alpha satellite DNA on most chromosomes of humans. PMID- 1909376 TI - Free left arms as precursor molecules in the evolution of Alu sequences. AB - The dimeric Alu molecule of human and other primates is composed of a left and a right arm that are very similar but show characteristic differences. If the Alu sequence has arisen through the fusion of monomeric precursor molecules, the traces of such precursor genes are expected still to be present in contemporary primate DNA. We report finding seven independent human DNA sequences that qualify as descendants of a left-arm precursor gene. Some characteristics in primary and secondary structures of these sequences are described. PMID- 1909377 TI - The main regulatory region of mammalian mitochondrial DNA: structure-function model and evolutionary pattern. AB - The evolution of the main regulatory region (D-loop) of the mammalian mitochondrial genome was analyzed by comparing the sequences of eight mammalian species: human, common chimpanzee, pygmy chimpanzee, dolphin, cow, rat, mouse, and rabbit. The best alignment of the sequences was obtained by optimization of the sequence similarities common to all these species. The two peripheral left and right D-loop domains, which contain the main regulatory elements so far discovered, evolved rapidly in a species-specific manner generating heterogeneity in both length and base composition. They are prone to the insertion and deletion of elements and to the generation of short repeats by replication slippage. However, the preservation of some sequence blocks and similar cloverleaf-like structures in these regions, indicates a basic similarity in the regulatory mechanisms of the mitochondrial genome in all mammalian species. We found, particularly in the right domain, significant similarities to the telomeric sequences of the mitochondrial (mt) and nuclear DNA of Tetrahymena thermophila. These sequences may be interpreted as relics of telomeres present in ancestral linear forms of mtDNA or may simply represent efficient templates of RNA primase like enzymes. Due to their peculiar evolution, the two peripheral domains cannot be used to estimate in a quantitative way the genetic distances between mammalian species. On the other hand the central domain, highly conserved during evolution, behaves as a good molecular clock. Reliable estimates of the times of divergence between closely and distantly related species were obtained from the central domain using a Markov model and assuming nonhomogeneous evolution of nucleotide sites. PMID- 1909378 TI - Protective effects of swainsonine on murine survival and bone marrow proliferation during cytotoxic chemotherapy. AB - We have investigated the ability of swainsonine, an indolizidine alkaloid with pleiotropic in vivo effects, to confer protection against the cytotoxic effects of both cell cycle-specific and cell cycle-nonspecific cytotoxic anticancer agents. The intraperitoneal administration of swainsonine decreased the lethality of methotrexate (MTX), fluorouracil (5-FU), cyclophosphamide (CPM), and doxorubicin (DOX) in non-tumor-bearing C57BL/6 mice. The increased survival rate was found to correlate with stimulation of bone marrow cell proliferation, as measured by increases in 1) bone marrow cellularity, 2) in vivo and in vitro colony-forming activity, and 3) engraftment efficiency. These responses were critically dependent on the dose, sequence, and timing of swainsonine administration. If these results are confirmed in humans, swainsonine may offer promise in future intensive chemotherapy programs, allowing increased dosage and/or frequency of administration of cytotoxic agents without increasing toxic effects in bone marrow. PMID- 1909379 TI - Expression and induction of intercellular adhesion molecules (ICAMs) and major histocompatibility complex (MHC) antigens on cultured murine oligodendrocytes and astrocytes. AB - Expression of intercellular adhesion molecule-1 (ICAM-1), ICAM-2-like molecule (Lgp55), and class I/II major histocompatibility complex (MHC) antigens (H-2 and Ia) was investigated in cultures of murine oligodendrocytes and astrocytes. Under unstimulated conditions, low levels of ICAM-1 expression were observed on astrocytes (less than 20%), but not on oligodendrocytes. Lgp55 was expressed intensely on oligodendrocytes (greater than 90%) and to a lesser degree on astrocytes (greater than 70%). A weak class I MHC (H-2) immunoreactivity was identified on both oligodendrocytes and astrocytes (50-70%). Class II MHC (Ia) antigen was undetectable on both cell types. After 48-hr exposure to immune mediators that include interferon-gamma (IFN-gamma), 500 U/ml, and supernatant from concanavalin A (Con A)-activated spleen cells, ICAM-1 expression was markedly increased on astrocytes (greater than 80%), but not on oligodendrocytes. Lgp55 expression on both cell types was not altered. Induction of H-2 antigen expression by immune mediators was quite high on both cell types (greater than 95%), while Ia antigen induction was low on astrocytes (less than 50%) and did not occur on oligodendrocytes. Cell type-specific expression and induction of ICAMs and MHC antigens by immune mediators may play roles in lymphocyte-glial cell interactions at the sites of inflammation in the central nervous system (CNS). PMID- 1909380 TI - Increased release of an amyloidogenic C-terminal Alzheimer amyloid precursor protein fragment from stressed PC-12 cells. AB - Amyloid plaques, found in characteristically large numbers in specific brain areas of Alzheimer's disease (AD) and Down's Syndrome (DS) patients, are composed of a 41-43 amino acid peptide, A4, derived from a transmembrane glycoprotein, amyloid precursor protein (APP). In transformed cells APP has been shown to be cleaved within the extracellular portion of the A4 region causing the release of 100-120 kDa soluble N-terminal APP products. If this cleavage occurs in human tissue, neither the soluble product nor the remaining 10-12 kDa transmembrane fragment could be further degraded to yield A4. It has been hypothesized that an alternate APP cleavage product containing the intact A4 region is released in increased amounts in AD and DS brain where subsequent extracellular degradation produces the amyloidogenic A4 peptide. In support of this hypothesis, we have found that PC-12 cells maintained in serum-free media with or without additional injurious agents release a 60 kDa protein which has been detected by immunoprecipitation and immunoblot analyses with 9 antisera elicited by 4 distinct peptides within the carboxyl-terminal half of APP. Six of these antisera, elicited by peptides corresponding to the carboxyl-terminal 20 amino acids of APP, or the A4 peptide itself, do not bind the normally released 120 kDa APP product which is detected by 11 other antisera elicited by peptides with the N-terminal portion of APP. Controls in which two 60 kDa-detecting antisera were preabsorbed with the peptides used to elicit them, produced markedly reduced 60 kd bands on immunoblots.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1909381 TI - Gene scene: factor VIII gene explains just half of severe cases of hemophilia A. PMID- 1909382 TI - Caring for the uninsured and underinsured. Another pound of cure. PMID- 1909383 TI - [A study on the treatment duration of an antibacterial agent in complicated urinary tract infections. Utility and recurrence after 14-day treatment by fleroxacin]. AB - In this study, fleroxacin (FLRX), a new quinolone derivative, was orally given at 300 mg once daily for 14 days to 102 patients with non-catheterized complicated urinary tract infections in order to determine the optimal treatment duration. We investigated its efficacy at day 5-7 and day 14, according to the criteria proposed by the Japanese UTI Committee, and also to the recurrence rate after the withdrawal. The results were as follows: 1. Overall clinical efficacy rates were 86% at day 5-7 and 84% at day 14. Both incidence of bacterial replacement in bacteriuria and normalization in pyuria were increased at day 14 as compared with those at day 5-7. 2. Bacteriological eradication rates were 91% at day 5-7 and 89% at day 14. 3. Clinical efficacy rates from physicians' evaluation were 86% at day 5-7 and 88% at day 14. 4. Incidence of side effects was 9.1%, and most of the cases were gastrointestinal symptoms which appeared within 4 days. Slight and transitory changes in laboratory findings were noted in 2.3% of evaluable cases. 5. With the occurrence of pyuria and bacteriuria as markers, the "no recurrence" rates were 63% at 1 week, 54% at 2 weeks, 61% at 3 weeks, 81% at 4-6 weeks after the withdrawal, and the "recurrence" rates were 4%, 4%, 6% and 5%, respectively. Remaining cases were judged as "reserved assessment". Generally, aggravation of bacteriuria was found but the aggravation of pyuria was observed in only few cases. 6. According to breakdown of cases with bacteriuria only, cure rate was 67% and recurrence rate was 33%. Re-infections were observed much more frequently than relapse based on the identification of infecting organisms. These results suggest that sufficient bacteriological eradication and clinical efficacy could be obtained by 14-day treatment of FLRX in non-catheterized complicated urinary tract infections. The efficacy of the treatment became evident around day 7. In approximately 30% of the cases in which eradication of the initial causative organisms was observed at day 14 reappearance of bacteriuria (greater than or equal to 10(3) CFU/ml) occurred after withdrawal of the antibiotic, but cases with pyuria were few, and the incidence of true recurrence was generally low. Onset of side effect after 5-day was not seen, hence FLRX seemed to be a safe agent. PMID- 1909384 TI - [Acute renal failure in patients with diabetes mellitus]. PMID- 1909385 TI - [Acute renal failure associated with miscellaneous drugs]. PMID- 1909387 TI - [C15O2 continuous inhalation technique (cerebral blood flow)]. PMID- 1909386 TI - [Recent advances in the treatment of acute renal failure]. PMID- 1909388 TI - [Striatal 18F-dopa uptake measuring nigrostriatal function]. PMID- 1909389 TI - [Pachydermoperiostosis--report of a case and review of 121 Japanese cases]. AB - A case of 23 years old man with idiopathic pachydermoperiostosis is reported. He showed cutis verticis gyrata, clubbed fingers and periosteal new bone formation without any causative basic disorder. His serum level of FSH, LH, estradiol and estriol were elevated, but their significance was not clear. Histological examination of the skin from the forehead revealed sebaceous hyperplasia and dermal thickening, where deposit of alcian blue and colloidal iron positive substance were detected. The deformed forehead and eyelids were corrected by plastic surgery. One hundred and twenty one cases of pachydermoperiostosis reported so far in Japan are briefly reviewed. Most of them were male (94.1%), about one fourth had a family history. The principal features are: clubbing of the digits (88.4%), periosteal new bone formation (94.1%), coarsening of the facial features with furrowing of the skin of the face (72.7%) and cutis verticalis gyrata (59.5%). Arthralgia (40.5%), hyperhidrosis of the feet and hands (44.6%), gastric hypertrophy (8 cases), gastric ulcers (5 cases) and endocrine abnormalities (17 cases) were also reported. PMID- 1909390 TI - Different modulation by cyclooxygenase inhibitors of the response to angiotensin II in monkey arteries and veins. AB - In coronary, renal and femoral arteries and mesenteric veins isolated from Japanese monkeys, tachyphylaxis to angiotensin (ANG) II (10(-7) M)-induced contraction rapidly developed. Contractions caused by ANG II in coronary arteries were attenuated by treatment with indomethacin and aspirin and also by endothelium denudation. Indomethacin inhibited the response of the arteries with and without endothelium to a similar extent. OKY 046, a thromboxane A2 synthesis inhibitor, failed to inhibit the response. In contrast, contractions of renal arteries were potentiated and prolonged by the cyclooxygenase inhibitors. ANG II induced contractions of mesenteric veins were prolonged but those of femoral arteries were not altered by indomethacin. It is concluded that ANG II contracts monkey coronary arteries, possibly due to the release of vasoconstrictor prostanoids but not thromboxane A2 from endothelial and subendothelial tissues and also due to its direct action on smooth muscle, whereas contractions of renal arteries and mesenteric veins are blunted by vasodilator prostanoids, possibly PGI2. Cyclooxygenase products even if released do not appear to regulate femoral artery contractions produced by ANG II. PMID- 1909391 TI - Inhibition of lipoxygenase by phenolic compounds. AB - Eugenol dose-dependently inhibited 5-HETE (5-hydroxy-5,8,10, 14-eicosatetraenoic acid) and 15-HETE formation by human polymorphonuclear leucocytes. p Chlorophenol, guaiacol and phenol also inhibited the lipoxygenases. Formation of HETEs by rat dental pulp was inhibited by eugenol and p-chlorophenol. The concentrations of the phenolics required to inhibit lipoxygenases were in the similar range with those used for inhibiting cyclooxygenase. These results showed that phenolic compounds inhibited lipoxygenases and thus suggest that these compounds may be dual inhibitors of lipoxygenase and cyclooxygenase. PMID- 1909392 TI - [Oxyhemoglobin dissociation curve and 2,3-diphosphoglycerate in chronic hypoxemia]. AB - The measurement of the oxyhemoglobin dissociation curve (ODC) and 2,3 diphosphoglycerate (2,3-DPG) in patients with chronic hypoxemia is important from the view point of tissue oxygenation. However, there have been no consistent results that explain the relation among chronic hypoxemia, 2,3-DPG and P50, which is oxygen pressure at an oxygen saturation of 50 percent. The aim of this study is to clarify what factors affect P50 and 2,3-DPG. 1) Patients with chronic hypoxemia, who showed PaO2 less than 60 Torr, had significantly higher P50 than normal subjects. 2) The concentration of Hb showed significant negative correlation with both P50 and 2,3-DPG. 3) Arterial blood pH showed significant positive correlation with both P50 and 2,3-DPG. 4) In a group with normal levels of Hb and pH, there was significant negative relationship between PaO2 and P50. 5) In a group with normal levels of Hb and pH, there was significant positive relationship between PaCO2 and P50. 6) In a group with normal levels of Hb, pH and PaCO2, there was significant negative relationship between PaO2 and 2,3-DPG. In conclusion, P50 and 2,3-DPG are affected largely by Hb concentration or blood pH, with or without hypoxemia. However there is a mechanism by which P50 and 2,3 DPG are increased by hypoxemia itself in a group with normal levels of Hb, pH and PaCO2. PMID- 1909393 TI - [A case of pericardial diverticulum with changing size]. AB - A 39 year-old woman with a tumor shadow in the right upper mediastinum noticed by chest x-ray examination of mass survey was presented. Chest x-ray films taken 5 times in a month in a same position showed the mass further changed in size. This result indicates the communication between the mass and pericardial cavity. Surgical extirpation was carried out and diagnosed a pericardial diverticulum. PMID- 1909394 TI - [Insulin secretion in non-insulin-dependent diabetes]. PMID- 1909395 TI - [Glycogen synthetase and non-insulin-dependent diabetes: role of gliclazide]. PMID- 1909396 TI - [Simultaneous corneal transplantation in mucopolysaccharidosis]. AB - We report the case of a 14 year old girl who obtained simultaneous penetrating keratoplasty for corneal opacity with functional loss as a consequence of a mucopolysaccharidosis typ Hurler/Scheie. Postoperatively, the host cornea displayed partial clearing. We discuss mechanisms possibly involved. PMID- 1909397 TI - Different clinical presentations of a lupus anticoagulant in the same family. AB - A young man who had suffered several episodes of deep-vein thrombosis of the legs since the age of 20 had a myocardial infarction at the age of 33, at which time both a prolonged partial thromboplastin time (PTT), compatible with a lupus anticoagulant (LA), and decreased fibrinolytic capacity (FC) were found. His sister presented with deep-vein thrombosis of a leg and subsequent pulmonary embolism when she was 18 years old. She had a miscarriage three years later and developed a hemolytic-uremic syndrome at the age of 35. The PT and FC were normal. Laboratory investigations of the parents revealed positive antinuclear antibodies in the mother's serum but no anomaly in the father. This study suggests a familial tendency to develop autoimmune disorders associated with LA and thromboembolic complications related to decreased FC. PMID- 1909398 TI - Kidney biopsy findings in cyclosporine-treated patients with insulin-dependent diabetes mellitus. AB - Renal biopsy specimens of 40 patients with recent-onset insulin-dependent diabetes mellitus treated with cyclosporine (CSA) for 6-29 months were examined. Cyclosporine-associated chronic vascular interstitial toxicity of moderate intensity was found in 10 patients (25%). The most prominent lesions were interstitial fibrosis and tubular atrophy. Arteriolopathy was less pronounced and glomerular damage unremarkable. A significant correlation exists between the extent of tubular atrophy and CSA trough whole blood levels. These data indicate that the development of CSA-associated chronic nephropathy is dose-dependent. PMID- 1909399 TI - Combined treatment with zidovudine and lymphoblast interferon-alpha in patients with HIV-related Kaposi's sarcoma. AB - A combination of oral zidovudine (250 mg twice daily) and subcutaneous interferon alpha (10 x 10(6) units daily) was evaluated for clinical, antiretroviral, and immunological efficacy and for side effects in 17 patients with AIDS-related Kaposi's sarcoma. Fifteen patients were evaluable. During the study period of 12 weeks, tumor responses were complete in two patients and partial in two patients (27% major response rate). Minimal responses were seen in two patients (40% overall response rate). An anti-HIV effect (reduction of serum p24 antigen by 70% or more) was observed in seven of ten evaluable patients who were initially antigenemic. CD4 lymphocyte counts remained unchanged. In six patients who had either a tumor response or a marked decline of HIV antigenemia, the treatment was continued between 12 and 59 weeks beyond the study period. Two of four patients with tumor regression at 12 weeks had an additional tumor response in this period despite prior dose reduction of interferon due to toxicity. Late progression of KS was eventually observed in four of six patients on prolonged treatment. The responsiveness of Kaposi's sarcoma seen in this study in patients with low CD4 counts and prior constitutional symptoms (fever, weight loss) was unexpected and needs further confirmation by larger patient groups. Dose-limiting toxicities were bone marrow depression (severe anemia in four and neutropenia with anemia in two patients), subjective adverse experiences (fever, fatigue, myalgia; four patients) and both (two patients).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1909400 TI - Use of 4-trifluoromethylumbelliferyl-alpha-L-iduronide as a new substrate for detection of alpha-L-iduronidase deficiency in human tissues and for rapid prenatal diagnosis of Hurler disease. AB - Results are presented of alpha-L-iduronidase assays in the leukocytes of normal individuals, patients with Hurler disease and heterozygous carriers. The assays were carried out using 4-methylumbelliferyl-alpha-L-iduronide and 4 trifluoromethylumbelliferyl-alpha-L-iduronide as substrates. It was shown that 4 trifluoromethylumbelliferyl-alpha-L-iduronide, along with the commonly used 4 methylumbelliferyl-alpha-L-iduronide, can serve as a specific substrate for alpha L-iduronidase and is therefore suitable for demonstrating the enzyme deficiency in patients with Hurler disease, as well as the decrease of enzyme activity in heterozygous disease carriers. Using the two substrates a prenatal diagnosis of Hurler disease in a fetus was made on the basis of the lack of enzyme activity in amniotic fluid cell cultures. The diagnosis was confirmed by the results of alpha L-iduronidase activity assay in fetal liver and kidney. It was found that 4 trifluoromethylumbelliferyl-alpha-L-iduronide is highly efficient for the rapid detection of alpha-L-iduronidase deficiency directly in pieces of tissues and in placenta, which is important for the prenatal diagnosis of Hurler disease. PMID- 1909402 TI - Atypical riboflavin-responsive glutaric aciduria, and deficient peroxisomal glutaryl-CoA oxidase activity: a new peroxisomal disorder. AB - Investigation of cultured skin fibroblasts in a patient with atypical riboflavin responsive glutaric acidura revealed a marked deficiency of peroxisomal glutaryl CoA oxidase. This is the first patient to be reported with glutaric aciduria caused by a peroxisomal rather than a mitochondrial dysfunction. This enzyme appears to be specific for glutaryl-CoA, as lauryl-CoA and dodecanedioyl-CoA oxidase activities in the fibroblasts were both normal. The urinary excretion of glutaric acid (0.5 mmol mmol creatinine-1) suggests that the flux through this pathway is considerably less than the mitochondrial flux through glutaryl-CoA dehydrogenase. The elevated glutaric acid excretion (to 0.8 mmol mmol creatinine 1) in response to lysine loading suggests that lysine is a precursor. PMID- 1909401 TI - Characterization of the mutations in three patients with pyruvate dehydrogenase E1 alpha deficiency. AB - The human pyruvate dehydrogenase complex catalyses the oxidative decarboxylation of pyruvate to acetyl-CoA. Defects in several of the seven subunits have been reported, but the majority of mutations affect the E1 component and especially the E1 alpha subunit. However, the clinical presentation of patients with pyruvate dehydrogenase E1 alpha deficiency is extremely variable. Dependency of the brain on pyruvate dehydrogenase activity and localization of the gene for the somatic form of the pyruvate dehydrogenase E1 alpha subunit to the X chromosome provide the basis for a better understanding of the variation in the clinical manifestations. Further understanding of the function and interaction of subunits and the pathophysiology of pyruvate dehydrogenase deficiency necessitates the characterization of mutations in the pyruvate dehydrogenase complex. We report the analysis of three patients with pyruvate dehydrogenase E1 alpha deficiency. One female has a three base pair deletion which affects dephosphorylation of the subunit. Of two males analysed, one has a two base pair deletion causing a shift in the reading frame. The other has a base change, resulting in an Arg to His substitution. All three mutations are located near the carboxyl terminus of the subunit. PMID- 1909403 TI - Neutral lipid storage disease with ichthyosis: serum apolipoprotein levels and cholesterol metabolism in monocyte-derived macrophages. AB - Neutral lipid storage disease with ichthyosis (NLSDI) is an inherited metabolic disorder characterized by accumulation of neutral lipids, in a wide variety of cells, by a still unknown mechanism. Previous studies have shown normal cholesterol content in NLSDI granulocytes, fibroblasts and skin cells. Monocyte derived macrophages possess an additional pathway of cholesterol uptake, which is not shared by these cells and which is not regulated by intracellular cholesterol levels. This pathway is thought to play a role in the process of atherosclerosis. Three NLSDI patients were studied. The serum levels of triglycerides, cholesterol, high-density lipoprotein cholesterol, and apolipoproteins A-I and B were within normal limits in all three patients. The intracellular levels of free and esterified cholesterol were measured in the monocyte-derived macrophages of one patient and found to be normal, while the triglyceride concentrations were twice as high as normal. The cholesterol esterification rates, which serve as a sensitive indicator of intracellular changes in cholesteryl ester levels, were normal in the monocyte-derived macrophages of all three patients. These findings provide further evidence that cholesterol metabolism is not disturbed in NLSDI, and it may be inferred that in this respect these patients are not at increased risk for atherosclerosis. PMID- 1909404 TI - Determination of serum apolipoprotein B by competitive enzyme-linked immunoassay. AB - An enzyme-linked immunoassay was used to determine apolipoprotein B (apoB) in serum samples from 104 healthy adults aged 18-26 years. The method was compared to radial immunodiffusion (RID). Mean apoB values were 103 +/- 30 mg/dl and 105 +/- 31 mg/dl respectively. The correlation coefficient for apoB between the two methods was r = 0.70, p less than 0.001; the correlation coefficient between LDL cholesterol and apoB measured by the ELISA was r = 0.73, p less than 0.001. This ELISA technique seems to be an appropriate method for measuring apoB in plasma, in the clinical laboratory and for detecting individuals with hyperapobetalipoproteinaemia. PMID- 1909405 TI - D-glyceric acidaemia: clinical report and biochemical studies in a patient. PMID- 1909406 TI - Canine carrageenin-induced acute paw inflammation model and its response to nonsteroidal antiinflammatory drugs. AB - A quantitative method for testing antiinflammatory agents in beagles has been developed, based on measurement of paw inflammation induced by a local injection of carrageenin. Carrageenin [0.5 mL of 2% (wt/vol) in saline] was injected into the plantar region of the hindpaws of pentobarbital-anesthetized beagles. Paw pressure changes registered from a water-filled balloon held on the top of the paw by a light adhesive tape wrapping were monitored for 240 min. In control dogs given 0.5% (wt/vol) methylcellulose (10 mL/kg orally) just before carrageenin, paw pressure increased significantly (p less than 0.05) over eightfold, from 2.9 +/- 0.8 mm Hg (mean +/- SEM, n = 29 paws) at 75 min to 26.0 +/- 3.5 mmHg at 240 min. The increase in paw pressure was significantly inhibited by the cyclooxygenase inhibitors, ibuprofen, indomethacin, and orpanoxin, and partially inhibited by the lipoxygenase inhibitor, phenidone, administered orally before carrageenin injection. Thus this model, with further characterization, could provide a convenient, quantitative way of assessing the efficacy of nonsteroidal antiinflammatory agents in dogs. PMID- 1909407 TI - Photochemically induced thrombosis model in rat femoral artery and evaluation of effects of heparin and tissue-type plasminogen activator with use of this model. AB - We report a new and reproducible model of thrombosis in the rat femoral artery. The thrombosis is initiated by endothelial injury subsequent to photochemical reaction between systemically injected rose bengal (10 mg/kg, i.v.) and transillumination of filtered xenon lamp (wave length: 540 nm) from the outside of the vessel. The blood flow of the femoral artery, which was monitored by a pulsed doppler flow meter, was fully stopped in 348.68 +/- 36.18 sec (n = 12) after i.v. injection of rose bengal under irradiation with green light. The formation of massive thrombosis was readily evident by visual inspection. The processes of primary endothelial injury and the subsequent formation of thrombosis during this manipulation were observed by light microscopy and analysed by the scanning and transmission electron microscopy. Pretreatment with heparin (30, 100 or 300 units/kg, i.v.) 10 min before rose bengal injection dose dependently prolonged the time required to interrupt the blood flow. The thrombolytic activity of a tissue-type plasminogen activator (tPA) was also investigated. After the establishment of stable thrombotic occlusion of the femoral artery, infusion of tPA was started from the contralateral femoral vein for 30 min at the rate of 30 or 100 micrograms/kg/min. The occluded artery was reperfused in 2 out of 10 rats and in 9 out of 12 at the lower and higher rates of tPA infusion, respectively. That heparin could prevent the arterial occlusion and that tPA could reperfuse the occluded artery are observations consistent with the histopathological ones that the primary lesion of endothelium injured photochemically activates the platelet aggregation to form platelet-rich thrombus with extensions of erythrocyte-rich lesions. This model is expected to be a useful tool for evaluating the antithrombotic and thrombolytic agents. PMID- 1909408 TI - Preferential rearrangement of developmentally regulated immunoglobulin VH1 genes in human B-lineage leukaemias. AB - Immunoglobulin heavy chain (IgH) variable region (VH) genes are rearranged and expressed in a programmed manner during B-cell development. In common with foetal/pre-immune B-cells, malignant B-lymphoid populations preferentially use a restricted repertoire of developmentally regulated VH genes. By nucleotide sequence analysis of polymerase chain reaction amplified IgH genes, we have compared the repertoire of VH1 family genes that are rearranged in mature, CD5+ B chronic lymphocytic leukaemia (CLL) with that in immature, CD5-B-lineage acute lymphoblastic leukaemia (ALL). The results revealed a non-random pattern pf VH1 usage in which no single VH1 family member was common to each of these disease groups. The VH1 gene, 51P1, which underlies an auto-antibody associated cross reactive idiotype, 'G6', frequently expressed on foetal B-cells, was preferentially rearranged in CLL (three of nine rearranged alleles). Another developmentally regulated VH1 gene, 20P3, accounted for more than half of the VH1 specific IgH gene rearrangements in ALL (five of nine VH1 alleles). Such developmentally restricted VH1 genes may distinguish discrete, although not necessarily exclusive, stages or compartments in B-lymphopoiesis from which each of these disease types arise. PMID- 1909409 TI - Multiple rearranged immunoglobulin genes in childhood acute lymphoblastic leukemia of precursor B-cell origin. AB - Sixty precursor B-cell acute lymphoblastic leukemia (ALL) patients were analyzed for the configuration of their immunoglobulin (Ig) genes. Rearrangements and/or deletions of the Ig heavy chain (IgH), Ig kappa chain (Ig kappa), and Ig lambda chain (Ig lambda) genes were detected in 98, 48, and 23% of cases, respectively. Although these percentages suggest the presence of a hierarchical order in IgH and Ig light chain (IgL) gene rearrangements during B-cell differentiation, no correlation was found between the immunophenotype of the precursor B-ALL and the arrangement patterns of their IgH and IgL genes. Multiple rearranged IgH gene bands, generally differing in density, were found in 27 (45%) of the precursor B ALL in various restriction enzyme digests. Cytogenetic data were used to determine whether the presence of more than two rearranged IgH gene bands was caused by hyperdiploidy of chromosome 14 or other chromosome 14 aberrations. The combined cytogenetic and IgH gene data allowed the precursor B-ALL to be divided into three groups: a monoclonal group (n = 36; 60%), a biclonal group (n = 16; 27%), and an oligoclonal group (n = 8; 13%). In five biclonal ALL biclonality at the Ig kappa gene level was also found. Such subclone formation was not detected at the Ig lambda gene level. As the detection limit of the Southern blot technique is 2-5%, it might well be that small subclones remained undetected, implying that the frequency of subclone formation at the IgH gene level in precursor B-ALL is probably higher than 40%. It has been suggested that precursor B-ALL with multiple IgH gene rearrangements have a higher tendency to relapse. Although higher relapse rates were found in the oligoclonal group (53%) and in the combined bi-oligoclonal group (33%) compared with the monoclonal group (20%), the log rank trend test showed no significance. The occurrence of multiple subclones in precursor B-ALL as found by IgH gene analyses will severely hamper the detection of minimal residual disease using the polymerase chain reaction (PCR) mediated amplification of 'tumor-specific' IgH gene junctional regions, because it cannot be predicted which detectable (or undetectable) subclone will cause minimal residual disease and/or relapse. Therefore it can be expected that the PCR technique will frequently produce false negative results during the follow-up of precursor B-ALL. PMID- 1909410 TI - Characterization of immunoglobulin heavy chain genes from an acute lymphocytic leukemia with four rearrangements. AB - Approximately 25% of acute leukemias of the B-cell lineage demonstrate more than two rearranged immunoglobulin heavy chain genes when examined by Southern blot analysis. The origin of the extra bands was investigated by molecular cloning and sequencing of four rearranged genes from one patient's leukemic cells. All four rearrangements were apparently derived independently. Two of the rearrangements used the VH6 variable region, attached to different diversity and joining regions. One of the two rearrangements contained a mutation in the coding sequence leading to the generation of a nonsense codon. This rearranged gene also differed from the other VH6 containing gene starting at about 330 bp upstream of the ATG initiation codon. The third rearranged gene used a member of the VH2 variable gene family. A DH-JH rearrangement was found in the fourth rearranged gene. The data indicate that the leukemia probably arose as a result of the transformation of an early B-cell progenitor that lacked rearranged immunoglobulin genes but retained some differentiation potential. PMID- 1909411 TI - An improved method for detection of B-lymphoid clonality by polymerase chain reaction. AB - Several groups have recently described methods for the detection of clonal immunoglobulin heavy chain (IgH) gene rearrangements in B-cell malignancies by polymerase chain reaction (PCR) gene amplification using variable region-(VH) and joining (JH) region-specific primers. The simplest methods utilize a single VH primer specific for sequences present in most VH regions corresponding to the third framework region (FR3). An alternative approach is to use a panel of VH family-specific primers specific for the first framework regions (FR1). In the course of nucleotide sequence analysis of IgH gene rearrangements amplified using a VH FR1 primer panel, these authors previously observed 3' VH region deletion and/or base mis-matches sufficient to prevent efficient priming from the VH FR3 primer target sequence in a significant minority of cases of B-lineage malignancy. An improved PCR method has therefore been developed by using a panel of seven VH FR1 family-specific primers incorporated in a single reaction. By using this method clonal IgH gene rearrangement is detected in 15 of 16 cases of B-lineage malignancy. Significantly, this series included four cases of B lymphoma in which previous attempts to detect PCR clonal IgH gene rearrangements using a VH FR3 primer were unsuccessful. In two of these cases, nucleotide sequence analysis of the amplified DNA showed that failure to prime with the VH FR3 primer was likely to be attributable to insufficient homology with the target sequence. The use of the approach described in this paper should significantly improve the reliability of detection of B-lymphoid clonality by PCR. PMID- 1909412 TI - The effect of the prostaglandin analogue-misoprostol on rat liver mitochondria after chronic alcohol feeding. AB - Rats fed ethanol (36% of total calories in a nutritionally adequate liquid diet) for 5 weeks develop functional alterations of hepatic mitochondria and steatosis of the liver. At the fatty liver stage, ADP-stimulated respiration of mitochondria was depressed in ethanol fed rats by 30% (p less than 0.001) with glutamate + malate and by 23% (p less than 0.001) with succinate as substrates. A similar decrease was noted in the respiratory control ratio (RCR) (34% and 29%, respectively). The total lipid content of the liver increased 2.6 fold (p less than 0.001). Mitochondrial dysfunction could be prevented, in part, by the treatment with a synthetic derivative of prostaglandin E1, misoprostol, at a mean daily dose of 80 micrograms/kg of body weight. The RCR with glutamate + malate as substrates was improved by 36% (p less than 0.05). We conclude that misoprostol attenuates several functional alterations in liver mitochondria during alcohol feeding. PMID- 1909413 TI - Immunological abnormalities in acute post-transfusion hepatitis non-A non-B. AB - A variety of immunological parameters has been serially examined in the blood of 12 patients with acute post-transfusion hepatitis non-A non-B (PTHNANB). Several alterations of these tests were transiently detected when comparing with healthy, extensively transfused subjects as well as with normal volunteers: 1. Low proportions of CD8+ T lymphocytes were observed at the disease onset, and these returned to normal after 1 month; 2. A diminution of the proliferative response of blood lymphocytes to mitogens was detected during the same period of time; 3. By the third month of disease, an enhanced spontaneous IgG secretion by cultured lymphocytes was found, and this observation was restricted to those patients who had not recovered. These alterations suggest that the immune system might be involved in the course of hepatitis C virus infection. PMID- 1909414 TI - Practical methods for chemical inactivation of Creutzfeldt-Jakob disease pathogen. AB - Chemical inactivation of pathogen of Creutzfeldt-Jakob disease (CJD) was examined using the mouse-adapted CJD strain. A high concentration of formic acid, guanidine compounds, trichloroacetate and phenol prevented CJD transmission. NaOH between 0.25 and 2 N lengthened the incubation periods. Sodium dodecyl sulfate (SDS) in a concentration between 1 and 3% did not alter incubation at room temperature but did completely block the transmission after boiling for 3 min in 3% SDS. This method is recommended for practical disinfection. PMID- 1909415 TI - [Pulmocare in pulmonary cachexia?]. PMID- 1909416 TI - [Effect of branched chain amino acid (BCAA) enriched solution in postoperative patients receiving TPN]. AB - Validity of branched chain amino acid (BCAA) enriched solution in surgical stress was assessed using total catecholamine excretion (U-CA) as the severity in dex. Thirty percent BCAA solution was infused no 21 patients (T group), and 21% BCAA to 18 patients (P group) pre and postoperatively. 2.0 g protein and 35 kcal/kg.day were provided by total parenteral nutrition (TPN). Correlation of nitrogen-balance to U-CA was statistically significant in both groups (p less than 0.01). The difference of correlations was statistically significant when analyzed by covariance (p less than 0.05). Rapid turnover proteins were significantly higher in T group, but no difference of urinary 3-methylhistidine excretion was observed. Increased uptake of BCAA and release of glutamine and alanine by skeletal muscle were observed. However, no alteration in arterio venous difference of phenylalanine and tyrosine was detected. In conclusion, 30% BCAA solution significantly improved postoperative protein metabolism, probably due to the improved visceral protein metabolism supported by amino acid supply by skeletal muscle. PMID- 1909417 TI - [Studies on nonthyroidal illness after heart surgery]. AB - The concentrations of pituitary hormones (TSH and PRL), thyroid hormones (free-T4 and free-T3), thyroid hormone binding protein (TBG) and lipids (TG and FFA) in the blood were measured in order to examine the physiology of nonthyroidal illnesses that occurred as a result of heart surgery as well as their effects on the pituitary and thyroid glands. The subjects of the study consisted of 30 adults with congenital and acquired heart disease. Blood concentrations of TSH, PRL, free-T4, free-T3, and TBG decreased, and those of FFA increased, on the 2nd day following surgery. On the 2nd day following surgery, the decrease in the concentrations of free-T4 and free-T3 in the blood were considered due to a decrease in secretion of T4 from the thyroid gland, as well as due to a decrease in the activity of iodothyronine 5'-deiodinase in the peripheral organs. In the 3rd week following surgery, the concentrations of these items returned to their original values on the day prior to surgery. PMID- 1909418 TI - Six nodulation genes of nod box locus 4 in Rhizobium meliloti are involved in nodulation signal production: nodM codes for D-glucosamine synthetase. AB - The nucleotide sequence of the nod box locus n4 in Rhizobium meliloti was determined and revealed six genes organized in a single transcriptional unit, which are induced in response to a plant signal such as luteolin. Mutations in these genes influence the early steps of nodule development on Medicago, but have no detectable effect on Melilotus, another host for R. meliloti. Based on sequence homology, the first open reading frame (ORF) corresponds to the nodM gene and the last to the nodN gene of Rhizobium leguminosarum. The others do not exhibit similarity to any genes sequenced so far, so we designated them as nolF, nolG, nolH and nolI, respectively. We found that the n4 locus, and especially the nodM and nodN genes, are involved in the production of the root hair deformation (Had) factor. NodM exhibits homology to amidotransferases, primarily to the D glucosamine synthetase encoded by the glmS gene of Escherichia coli. We demonstrated that in E. coli the regulatory gene nodD together with luteolin can activate nod genes. On this basis we showed that nodM complemented an E. coli glmS- mutation, indicating that nodM can be considered as a glmS gene under plant signal control. Moreover, exogenously supplied D-glucosamine restored nodulation of Medicago by nodM mutants. Our data suggest that in addition to the housekeeping glmS gene of R. melioti, nodM as a second glmS copy provides glucosamine in sufficient amounts for the synthesis of the Had factor. PMID- 1909419 TI - Gene disruption by plasmid integration in Listeria monocytogenes: insertional inactivation of the listeriolysin determinant lisA. AB - A plasmid integration technique was developed for insertional inactivation of chromosomal Listeria monocytogenes genes. A Listeria-Escherichia coli shuttle vector (pLSV1) was constructed which carried the temperature-sensitive gram positive replication origin from plasmid pTV32(Ts). An internal fragment of the listeriolysin gene (lisA) was cloned into pLSV1 to create pLSV2. In L. monocytogenes pLSV2 transformants, plasmid pLSV2 integrated into the L. monocytogenes chromosome at a frequency of 2 x 10(-3) via lisA homology and these cells could be selected at 42 degrees C using a plasmid-encoded erythromycin resistance. Plasmid integration resulted in disruption of the lisA gene, production of a truncated, immunologically cross-reactive listeriolysin protein and loss of the hemolytic phenotype. An improved Listeria protoplast transformation method is also described which facilitates genetic manipulation of Listeria species. PMID- 1909420 TI - Intercistronic group III introns in polycistronic ribosomal protein operons of chloroplasts. AB - A novel ribosomal protein operon in the Euglena gracilis chloroplast genome was characterized. It encodes the genes for ribosomal proteins S4 and S11 (rps4 and rps11). The coding region of the rps11 gene is interrupted by two introns of 107 and 100 bp. The introns belong to a distinct class known as group III introns. The major transcript from this operon was characterized as a fully spliced dicistronic rps4-rps11 mRNA by RNA blot analysis, primer extension sequencing, and cDNA cloning and sequencing. An additional 95 nucleotide (nt) group III intron was identified in the 123 nt rps4-rps11 intercistronic region. The identification of the intercistronic intron between the rps4 and rps11 genes was unexpected. Other RNA transcripts from regions of the genome that could potentially contain intercistronic introns were re-examined and two other intercistronic, group III introns were found. These are located in a large ribosomal protein operon between the genes for the ribosomal proteins L23 and L2, and between L14 and L5. There are at least 50 group III introns in the E. gracilis chloroplast genome. All but 6 are found in genes encoding protein components of the transcriptional and translational apparatus. The distribution of group III introns and the unusual location of intercistronic group III introns may reflect some aspect of gene expression, or provide some insight into the mechanism of their splicing. PMID- 1909421 TI - Localization and orientation of the VirD4 protein of Agrobacterium tumefaciens in the cell membrane. AB - The virD4 gene of Agrobacterium tumefaciens is essential for the formation of crown galls. Analysis of the nucleotide sequence of virD4 has suggested that the N-terminal region of the encoded protein acts as a signal peptide for the transport of the VirD4 protein to the cell membrane of Agrobacterium. We have examined the localization and orientation of this protein in the cell membrane. When the nucleotides encoding the first 30 to 41 amino acids from the N-terminus of the VirD4 protein were fused to the gene for alkaline phosphatase from which the signal sequence had been removed, alkaline phosphatase activity was detectable under appropriate conditions. Immunoblotting with VirD4-specific antiserum indicated that the VirD4 protein could be recovered exclusively from the membrane fraction of Agrobacterium cells. Moreover, when the membrane fraction was separated into inner and outer membrane fractions by sucrose density gradient centrifugation, VirD4 protein was detected in the inner-membrane fraction and in fractions that sedimented between the inner and outer membrane fractions. By contrast, the VirD4'/alkaline phosphatase fusion protein with the N terminal sequence from VirD4 was detected only in the inner membrane fraction. Treatment of spheroplasts of Agrobacterium cells with proteinase K resulted in digestion of the VirD4 protein. These results indicate that the VirD4 protein is transported to the bacterial membrane and anchored on the inner membrane by its N terminal region. In addition, the C-terminal portion of the VirD4 protein probably protrudes into the periplasmic space, perhaps in association with some unidentified cellular factor(s). PMID- 1909422 TI - Inactivation of lacZ gene expression by UV light and bound DNA photolyase implies formation of extended complexes in the genomes of specific Escherichia coli strains. AB - In Escherichia coli strains WU and CS101, UV inactivation of lacZ gene expression is more effective when the cells contain amplified DNA photolyase, and flash photoreactivation (fPR) after 15 min of metabolism does not reverse inactivation by the photolyase-dimer complexes. In other strains, also studied with or without amplified DNA photolyase, there is no differential UV inactivation and fPR reverses inactivation by the complexes regardless of continued metabolism. The irreparable condition in strain WU is not due to dysfunction of photolyase: during post-UV metabolism, fPR still restores viability and dimers are removed from the region of the lac operon. When the wild-type lac promoter is replaced by the UV5 promoter, making expression insensitive to relaxed supercoiling and catabolite repression, inactivation by dimers alone becomes more resistant, i.e. requires higher fluences, but inactivation in WU and CS101 is still exceptionally sensitive to photolyase-dimer complexes. This indicates that dimers external to the wild-type lac operon may inhibit expression by altering supercoiling but that complexes must involve some other mechanism for their special effect in WU and CS101. The exceptionally efficient inactivation and irreparable condition are consistent with the idea that, in two specific laboratory strains, photolyase bound to dimers at a considerable distance from the lac operon may initiate an aggregation of DNA with other cellular molecules that extends to, and inactivates expression from, the operon. PMID- 1909423 TI - Egg production and fertility in Drosophila depend upon the number of yolk-protein gene copies. AB - The yolk proteins of Drosophila melanogaster comprise a family of three related yolk polypeptides each encoded by a single-copy gene. We show by genetic crosses that each gene makes an equivalent contribution to the fecundity and fertility of the female and they do not individually provide unique functions to the embryo. We show that the number of eggs laid by a female depends upon the number of genes encoding yolk polypeptides present in the genome and furthermore that the probability of an egg hatching into an adult also critically depends upon the number of yolk protein genes present in the mother. This suggests that the three yolk protein-encoding genes in Drosophila melanogaster may have arisen by duplication, then been maintained for quantitative reasons because they increased egg production and fertility, rather than each protein evolving a different function as is the case with most small gene families, such as tubulins and collagen genes. PMID- 1909424 TI - Cloning, sequencing and expression of a gene encoding a 73 kDa xylanase enzyme from the rumen anaerobe Butyrivibrio fibrisolvens H17c. AB - The cloning, expression and nucleotide sequence of a 3 kb DNA segment on pLS206 containing a xylanase gene (xynB) from Butyrivibrio fibrisolvens H17c was investigated. The open reading frame (ORF) of 1905 bp encoded a xylanase of 635 amino acid residues (Mr 73156). At least 850 bp at the 3' end of the gene could be deleted without loss of xylanase activity. The deduced amino acid sequence was confirmed by purifying the enzyme and subjecting it to N-terminal amino acid sequence analysis. In Escherichia coli C600 (pLS206) cells the xylanase was localized in the cytoplasm. Its optimum pH for activity was between pH 5.4 and 6, and optimum temperature 55 degrees C. The primary structure of the xylanase showed a significant level of identity with a cellobiohydrolase/endoglucanase of Caldocellum saccharolyticum, as well as with the xylanases of the alkaliphilic Bacillus sp. strain C-125, B. fibrisolvens strain 49, and Pseudomonas fluorescens subsp. cellulosa. PMID- 1909426 TI - [Perioperative total parenteral nutrition. Our experience]. AB - The Authors analyze the results of 83 cases of TPN in a surgical department after a revision of the literature from which it comes out how such a method has been proposed to reduce the catabolism by surgical trauma of fasting, especially after greater surgical operations. PMID- 1909425 TI - Characterization, molecular cloning and sequencing of YP3s1, a fertile yolk protein 3 mutant in Drosophila. AB - The three yolk proteins (YP1, YP2 and YP3) of Drosophila melanogaster are synthesized in two tissues of the adult female, the fat body and ovarian follicle cells. The YPs are selectively accumulated in the oocyte to provide nutrients for embryogenesis. We describe a female-sterile mutant, fs(1) A1526, which lacks YP3 in the haemolymph. The female sterility mutation mapped some distance away from the yp3 gene on the X chromosome and we were able to separate the YP3 defect from the female sterility by recombination, thus producing a fertile line of flies having no YP3 in the eggs. This shows that YP3 is not essential for embryogenesis. The mutant line is to be known as YP3s1. Investigation of yp3 transcription in the mutant females revealed that the gene is transcribed but yp3s1 mRNA levels are reduced relative to wild type. Transcription of the mutant yp3 gene can be induced in males by ecdysone. Investigation of the yolk proteins in YP3s1 females suggested that the YP3s1 polypeptide is synthesized in the fat body but not secreted. The mutant YP3 protein shows an increase in apparent molecular weight of approximately 1 kDa. The mutant yp3 gene was cloned and the DNA sequence determined. The sequence differences between the mutant and wild type genes include an amino acid substitution in the leader sequence. We suggest that this may be responsible for the failure of YP3 secretion in the mutant YP3s1, and speculate on the cause of the reduction seen in the steady-state level of yp3 mRNA. PMID- 1909427 TI - [Association of pheochromocytoma and phakomatosis. Apropos of a clinical case]. AB - Of the multiple endocrine syndromes, the association between pheocromochytoma, medullary thyroid carcinoma (MTC) and parathyroid-hyperplasia (Sipple's syndrome, MEN IIa), and the association of MTC, with multiple monocutaneous neuromas and with a characteristic facial appearance (MEN IIb syndrome) are well known. Furthermore in about 10% of the patients affected by Von Recklinghausen's disease (neurofibromatosis) a pheocromochytoma is present. A new classification of this important (even though rare) chapter of endocrine pathology was developed by Pears in 1968 when he hypothesized a common neuroectodermic origin for groups of cells diffused throughout the body and nested in different organs. The association of such different pathological conditions could be justified by a faulty development of these primitive neuroectodermic cells. This study aim to analyse a recently observed case of pheocromochytoma associated with Von Recklinghausen's disease. The Pathogenetic hypotheses of this rare pathological association, the diagnostic methods and the therapeutic procedures will be review. PMID- 1909428 TI - Mutagenesis of the DNA contact site in Fos protein: compatibility with the scissors grip model and requirement for transformation. AB - To elucidate the mechanisms involved in the transformation by fos we have initiated a study pertaining to the identification of molecular functions of Fos protein that are crucial for transformation. We have previously reported that the presence of an intact leucine zipper in Fos is an absolute requirement for the induction of transformation, but that the autorepression function of Fos is dispensable. We now show that Fos protein also needs an intact DNA (TRE)-binding site to be able to transform. Amino acid substitutions in this domain of Fos which impair DNA binding also destroy the transforming potential of Fos, suggesting that the interaction of Fos-Jun complexes with TREs may be a crucial part of Fos-induced transformation. This hypothesis is further strengthened by our observation that Fos and Jun can cooperate in the induction of transformation. We show that a Fos protein which contains a Jun leucine zipper and is thus capable of dimerization is still dependent on the presence of exogenous Jun to induce transformation. The critical positions in the Fos DNA binding site include those which the 'scissors grip' model predicts to be crucial, although the DNA-binding site in Fos seems to extend beyond the basic region into an adjacent cluster of acidic amino acids. PMID- 1909429 TI - Regulation of Egr-1 (Zfp-6) and c-fos expression in differentiating embryonal carcinoma cells. AB - The Egr-1 gene (zfp-6) encodes a 'zinc finger'-type transcription factor that is one of the early growth response genes induced, together with c-fos proto oncogene, in many cell types. Our earlier work indicated that Egr-1 and c-fos may also play roles in differentiation and we now present data to show some features of their regulation. Transcriptional regulation accounts at least partly for the increased steady-state levels of Egr-1 mRNA in differentiating teratocarcinoma cells; this rate increases threefold over the 7-10 days of differentiation of P19 embryonal carcinoma cells with both 0.5% DMSO (to give predominantly cardiac muscle) and 1 microM retinoic acid (to give nerve and glial cells). The stability of Egr-1 transcripts remains the same (T1/2 = 90 min) in undifferentiated EC and differentiated cell products. In contrast, transcripts for c-fos are barely detectable in EC cells and increase 20-fold during differentiation. The basis for this is a marked increase in stability of c-fos mRNA after differentiation. The protein products of both genes parallel the steady-state levels of their mRNAs, but both proteins become more stable in differentiated cells. This is particularly marked for c-Fos protein, which appears as a distinct 58 kDa species in terminally differentiated P19 cells. Both Egr-1 and c-Fos proteins remain at high constitutive levels in differentiated cells indicating a distinct role for these transcription factors, For instance, it appears that this form of Fos protein may not repress the synthesis of the Egr-1 gene as it does during transient expression of serum-stimulated genes. PMID- 1909430 TI - Mutations in the thymidine kinase gene that allow expression of the enzyme in quiescent (G0) cells. AB - Thymidine kinase (TK) is a nucleotide salvage pathway enzyme whose activity is highly dependent on the growth state and cell cycle phase of a cell. Cells in the resting or quiescent (G0) phase express very low levels of TK mRNA and protein. When quiescent cells are stimulated to enter the cell cycle by the addition of serum, TK mRNA, activity and polypeptide increase coordinately after about 10-15 h, at the beginning of S phase. When growth-independent heterologous promoters are substituted for the natural TK promoter, TK mRNA can be expressed in quiescent cells. Despite the presence of TK mRNA in such G0 cells, there is little expression of TK polypeptide; the normal increase in enzyme at S phase is observed following serum stimulation. Deletion of the introns and 3' untranslated sequences does not affect the expression of the TK gene in serum stimulation experiments. In contrast, deletion of the C-terminal 40 amino acids or fusion of a small segment of a beta-galactosidase to the C-terminus overcomes the block to expression of the TK polypeptide in G0 cells. These C-terminal alterations are the same as those which lead to constitutive expression of TK during the cell cycle of proliferating cells, suggesting that mechanisms which control the levels of TK in cycling cells may also operate in quiescent cells. PMID- 1909433 TI - Nucleotide sequence of a 16S rRNA gene from Anabaena sp. strain PCC 7120. PMID- 1909431 TI - Functional modularity in the SP6 kappa promoter. AB - The requirements of the SP6 kappa promoter for transcriptional activation were studied in nontransformed murine B lymphocytes stimulated with lipopolysaccharide. Three different DNA motifs, besides the TATA-box, were needed for restoration of transcriptional activation to the same magnitude as seen with the native SP6 kappa promoter. The decamer motif (TNCTTTGCAT) was found to induce transcription alone and point-mutation of this element reduced transcription to negligible levels, although the other two required elements were present. The penta-decamer element (TGCAG/CCTGTGNCCAG) did not stimulate transcription alone, but activated transcription synergistically in conjunction with the decamer motif. This synergism required the presence of a third pyrimidine rich element (CCCT) in the decamer 3' flanking sequence. The pyrimidine rich element could partly be substituted for by an E-box core motif (CANNTG) 3' of, but not by the kappa Y motif (CTTCCTTA) 5' of, the decamer. Proteins interacting specifically with the penta-decamer element were detected by band-shift assay. The decamer 3' flanking sequence of the SP6 kappa promoter was found to modify the binding of endogenous Oct2 isoforms to the decamer motif i B lymphocytes, but not in CHO cells transfected with various Oct2 isoforms. Thus, complex protein/DNA interactions can be observed in the SP6 kappa promoter which correlate functionally with a synergism in transcriptional activation. PMID- 1909432 TI - Further sequence requirements for male germ cell-specific expression under the control of the 14 bp promoter element (beta 2UE1) of the Drosophila beta 2 tubulin gene. AB - We have investigated a 14 bp promoter element (beta 2UE1) that is required for testis-specific expression of the Drosophila beta 2 tubulin gene. To further elucidate the role of the 14 bp element, we fused different promoter constructs to the E. coli lacZ gene and established transgenic strains with the aid of the Drosophila P-element transformation system. Germ line transformation experiments with constructs in which the element in the beta 2 tubulin gene promoter was exchanged for a related sequence from the promoter region of the Drosophila beta 3 tubulin gene led to a dramatic reduction in the expression of the lacZ gene in the testis. Exchanging the 14 bp promoter element for a similar sequence from the distal promoter of the Drosophila alcohol dehydrogenase gene abolished expression. This might indicate that the sequence differences between the beta 2UE1 and the beta 2UE1-related elements reflect functional differences between these elements. Constructs in which the beta 2UE1 was fused to the hsp70 promoter revealed that testis-specific expression of a marker gene is obtained only when the element is located at the correct distance from the transcription initiation site. However, constructs in which the beta 2UE1 was inserted at about the correct position (between -41 and -54 bp) upstream of a truncated beta 3 tubulin gene promoter did not show any expression. By making beta 2-beta 3 gene promoter fusions it was found that both the region surrounding the beta 3 transcription initiation site as well as the first 116 b of beta 3 leader sequences independently reduce testis-specific expression. These findings suggest that the testis-specific expression of the Drosophila beta 2 tubulin gene underlies a unique regulatory mechanism. PMID- 1909434 TI - A method for cDNA cloning in COS cells irrespective of subcellular site of expression. PMID- 1909435 TI - Dinucleotide repeat polymorphism in Gs-alpha subunit gene (GNAS1) on chromosome 20. PMID- 1909437 TI - Detection of a TaqI polymorphism within the human TPA gene (PLAT). PMID- 1909436 TI - Mononucleotide repeat polymorphism in the APP gene. PMID- 1909438 TI - Research note: effect of excess lysine, methionine, threonine, or tryptophan on production performance of laying hens. AB - An experiment was conducted with laying hens to determine effects of feeding excesses of several individual amino acids in a practical layer diet. Single Comb White Leghorn hens, which were in peak production (31 wk of age), were assigned to one of five dietary treatments: a 16% CP corn and soybean meal positive control diet, or this diet fortified with 1% additional L-Lys, 1% additional DL Met, 1% additional L-Thr, or 1% additional L-Trp. The diets were fed for ad libitum intake for 4 consecutive wk of production. For the entire production period, hen-day egg production, egg yield, and feed intake were not significantly different among any of the treatments. The study indicated that considerable tolerance exists in high-producing laying hens for individual excesses of the amino acids commonly used as supplements in poultry diets. PMID- 1909439 TI - Synthesis and degradation of eicosanoids in primary rat hepatocyte cultures. AB - Arachidonic acid metabolites may play an important role in liver physiology, yet hepatocyte prostaglandin synthesis has not been characterized extensively. We used RIA to study production and clearance of several eicosanoids in confluent primary cultures of rat hepatocytes in serum-free, hormonally-defined medium. Under basal, unstimulated conditions 6-keto-PGF1 alpha (spontaneous breakdown product of prostacyclin) and 13,14-dihydro-15-keto-PGE (DHK-PGE, a metabolite of PGE) accumulated in the culture medium. Hepatocytes cleared 6-keto-PGF1 alpha, thromboxane B2, and DHK-PGE from the medium. Production of eicosanoids by primary cultures appeared resistant to indomethacin and several other cyclooxygenase inhibitors. This apparent resistance to indomethacin was not caused by rapid metabolism of indomethacin, by failure of the drug to enter hepatocytes, or by insensitivity of hepatocyte cyclooxygenase to the drug. Metabolism of PGE to DHK PGE may be saturated under in vitro conditions. Hepatocytes can synthesize significant amounts of eicosanoids, although they are probably less active in this regard than are non-parenchymal cells. PMID- 1909440 TI - Actions of gallic esters on the arachidonic acid metabolism of human polymorphonuclear leukocytes. AB - Gallic esters with a varying chain length of its alcohol moiety produced strong inhibition of the conversion of [1-14C]-arachidonic acid to 5S-hydroxy 6E,8Z,11Z,14Z-eicosatetraenoic acid (5-HETE) by isolated human polymorphonuclear leukocytes. Octyl gallate and decyl gallate were the most powerful inhibitors with a concentration of half-inhibition of about 1 mumol . 1-1. Additionally these compounds caused however at 10 mumol . 1-1 a complete inhibition of the incorporation of arachidonic acid in triacylglycerols and phospholipids which is assumed to be a consequence of the damage to the energy metabolism of the cells. In contrast, the other gallic esters enhance the incorporation of arachidonic acid in the ester lipids in addition to moderate inhibition of the 5-lipoxygenase pathway. PMID- 1909441 TI - Amino acid and NaCl appetite, and LHA neuron responses of lysine-deficient rat. AB - Rats' preferences for amino acids and NaCl in their drinking behavior were noted when they were fed either a control diet of gluten plus 20% purified egg protein, or (same rats, different time) a lysine-deficient diet. In control, the order of the rats' preferences was arginine greater than saline greater than monosodium L glutamate (MSG, umami) greater than glycine greater than water greater than threonine greater than histidine greater than lysine. When fed a lysine-deficient diet the order of preference was lysine greater than saline greater than MSG greater than glycine greater than threonine greater than water greater than arginine greater than histidine. To relate neural activity with preference for amino acids and NaCl, activity of lateral hypothalamic (LHA) neurons was recorded during ingestion of MSG, lysine, arginine, glycine, saline, glucose, or water by the control and lysine-deprived condition, following a different cue tone. When the diet was lysine deficient, some neurons responded specifically to lysine ingestion. More neurons responded nondifferentially during licking in control, and responded to lysine, but fewer to other amino acid ingestion during lysine deficiency. Responses to cue tone were associated with those during licking. The present results suggest that preference for deficient amino acids might be mediated in the LHA. PMID- 1909442 TI - [Long-term treatment of chronic psychiatric patients--a rewarding responsibility]. AB - Psychotherapy is generally believed to be insight-oriented, and functional psychoses to be incurable and inaccessible for a psychotherapeutic approach. The present paper demonstrates through a concrete example that even a severe and chronic schizophrenia can be cured with special psychotherapeutic means. Such an attempt may seem unending, troublesome, and laborious, but by setting adequate goals, such an attempt is often very successful and therefore rewarding. A modern theoretical framework of psychiatric illness and a corresponding treatment approach are described. PMID- 1909443 TI - [Psychoanalytic aspects in long-term management of hospitalized chronic psychotic patients]. AB - This article reflects the experience of several years in the treatment of long term hospitalized chronic psychotic patients. The point of view is psychoanalytic; the background is given by the modern Ego Psychology in the meaning of Blanck and Blanck and the Object-relations Theory in the Kernberg version. Special remarks are made on the phenomenon of regression. PMID- 1909444 TI - A functional-dimensional approach to depression: serotonin deficiency as a target syndrome in a comparison of 5-hydroxytryptophan and fluvoxamine. AB - H.M. van Praag has been suggesting a reappraisal of syndromes in psychiatry for over 20 years. He has tried to define syndromes originating from the same biochemical disorder. He has denoted this concept as 'functional psychopathology'. As an example of such a functional syndrome, he has cited the serotonin-shortage syndrome which unifies various psychiatric symptoms under a new point of view. The treatment of the serotonin-shortage syndrome is best served by psychopharmaca which raise the metabolism of serotonin in the synaptic cleft, e.g. the selective serotonin re-uptake inhibitors. Borrowing F. Freyhan's concept of 'target symptoms', one can now speak of 'functional target syndromes', within the frame of functional psychopathology. PMID- 1909445 TI - Hyperintense basal ganglia on T1-weighted MR images in patients receiving parenteral nutrition. AB - Patterns of intracranial signal intensity on magnetic resonance (MR) images were studied in nine patients undergoing long-term total parenteral nutrition therapy. The duration of therapy ranged from 5 months to 11 years (mean, 5.3 years). Symmetric increased signal intensity on T1-weighted MR images (hyperintense relative to white matter) was observed in the basal ganglia of all patients, without corresponding abnormality on T2-weighted images. Analysis of signal intensity characteristics and distribution pattern suggests that the basis for these changes may be deposition of intravenously administered paramagnetic trace elements, especially manganese, and/or an astrogliotic reaction to such deposition. PMID- 1909447 TI - Quantitative assessment of quality of digitized portal images: receiver operating characteristic analysis applied to imaging in radiation therapy. AB - An objective and quantitative method for the evaluation of the quality of megavoltage portal images was developed by applying receiver operating characteristic analysis. On the basis of therapeutic use of portal images, setup errors were employed as "signals" in this experimental study that compared the original portal films with digitized images. Six readers observed 104 portal images of a chest phantom, half of which were "abnormal" (ie, had setup errors). Digital images (2,048 x 2,048 matrix) were enhanced by means of histogram equalization and then printed with a laser printer for observation. The readers showed a higher discrimination capacity with the digitally enhanced images, although a statistically significant improvement was not demonstrated. The present method of assessment of image quality proved to be both simple and clinically reasonable. PMID- 1909446 TI - Marshall-Smith syndrome: new radiographic, clinical, and pathologic observations. AB - Radiographic, clinical, and histologic findings in two infants and a neonate with a syndrome of profoundly accelerated skeletal maturation included features closely resembling those of Marshall-Smith (MS) syndrome, but patients had dysmorphic ears as well as distinctive generalized skeletal abnormalities suggestive of a bone dysplasia. Among these was an instability at the craniocervical junction with severe spinal stenosis. These previously unrecognized abnormalities may represent uncommon manifestations within the spectrum of MS syndrome or indicate the existence of a separate disorder. PMID- 1909448 TI - Your patient and angina. PMID- 1909450 TI - Intrathoracic meningocele in a patient with neurofibromatosis. PMID- 1909449 TI - The Patient Intensity for Nursing Index: a validity assessment. AB - The psychometric assessment of a new measure of nursing intensity, The Patient Intensity for Nursing Index (PINI) is reported. Four dimensions of nursing intensity are measured by the PINI: (a) severity of illness, (b) dependency, (c) complexity of care, and (d) time. There are 10 items rated on a 5-point ordinal scale. A purposively drawn sample of 6,445 patients was obtained from five hospitals, with 487 registered nurses (RNs) providing daily patient ratings from 29 medical-surgical and intensive care units. Substantial interrater reliability was demonstrated. Validity testing included confirmatory factor analysis, hypothesis-testing, contrasted groups, and an observational study of time. The factor structure confirmed specified components of severity, dependency, and complexity, with time loading on all three factors. PINI scores were significantly related to medical severity of illness, length of hospital stay, disposition at discharge, number of secondary medical diagnoses and specialty consults, and scores on three different hospital classification systems used for staffing. PINI scores were significantly different for high- and low-intensity DRGs. Observed time spent delivering nursing care to specific patients was significantly correlated with nurse estimates of time. PMID- 1909451 TI - [An analysis of the nursing care given to the child on parenteral nutrition]. AB - The purpose of this study was to collect information on nursing car of children receiving parenteral nutrition in order to gain knowledge to improve nursing care according to the resources available in the hospital. Our results showed that in the three hospitals studied there were no adequate physical space to prepare parenteral nutrition. There were no suitable accommodations for the children, the nursing care on P.N. were not standardized and the follow up was not well done. PMID- 1909452 TI - Interaction between Pseudomonas aeruginosa and host defenses in cystic fibrosis. AB - The major causes of morbidity and mortality in cystic fibrosis are chronic pulmonary obstruction and infection. Mucoid Pseudomonas aeruginosa is the primary pathogen in up to 90% of these patients. Once Pseudomonas organisms colonize the airways, they are virtually never eradicated. No defect in systemic host defense has been elucidated, however, several mechanisms contribute to the breakdown in host defenses that allow persistence of this organism in the endobronchial space. These mechanisms involve both bacterial adaptation to an unfavorable host environment and impaired host response. P aeruginosa adapts to the host by expressing excessive mucoid exopolysaccharide and a less virulent form of lipopolysaccharide. These features make it less likely to cause systemic infection, yet still enable it to resist local host defenses. Mucociliary clearance becomes impaired due to abnormal viscoelastic properties of sputum, squamous metaplasia of the respiratory epithelium, and bronchiectasis. Despite a brisk antibody response to a variety of Pseudomonas antigens, several defects in antibody-mediated opsonophagocytosis have been identified. These include (1) development of antibody isotypes that are suboptimal at promoting phagocytosis, (2) formation of immune complexes that inhibit phagocytosis, and (3) proteolytic fragmentation of immunoglobulins in the endobronchial space. Complement-mediated opsonophagocytosis is also compromised by proteolytic cleavage of complement receptors from the cell surface of neutrophils and complement opsonins from the surface of Pseudomonas. The resultant chronic inflammation and infection lead to eventual obliteration of the airways. PMID- 1909453 TI - Host determinants of susceptibility to Mycobacterium tuberculosis. AB - Susceptibility to tuberculosis is determined by a number of host factors and may vary according to characteristics of the infecting strain. Native resistance is probably mediated via the macrophage and is under genetic control. Other factors that contribute to native resistance are nutrition, associated disease states, age, and sex. Acquired resistance is mediated via macrophages and controlled by T helper cells. The ability of an activated macrophage to phagocytize and kill virulent tubercle bacilli is influenced by the function and number of T-helper cells. The macrophages are affected by concurrent disease states and immunosuppressive drugs. Macrophages provide local immunity, once activated, and T-helper lymphocytes provide the long-term systemic immunity. PMID- 1909454 TI - [Parathyroid function in hyperthyroidism: implications for bone metabolism and effect of the treatment]. AB - PURPOSE: using bone densitometry, to evaluate bone loss of hyperthyroidism patients, and to study the possible contribution of parathyroid hormone (PTH) in the genesis of this osteopenia. TYPE: prospective study of patients with hyperthyroidism before and after treatment. PLACE: Division of Endocrinology, Escola Paulista de Medicina. Sao Paulo, SP. PATIENTS: 14 outpatients with clinical and laboratory diagnosis of toxic diffuse goiter (Basedow-Graves disease). Six of these patients were studied again after treatment, with at least 6 months of clinical and laboratory euthyroidism. METHOD: bone mineral content of the lumbar vertebral bodies was evaluated by dual-photon bone densitometry. Parathyroid hormone secretion was studied with an amino-terminal specific assay after EDTA-induced hypocalcemia; results were compared to those obtained from a group of 10 normal controls. RESULTS: there was a significant increase in bone mineral density after treatment (1.300 +/- 0.079 g/cm2) as compared to the pre treatment condition (1.229 +/- 0.091 g/cm2, p less than 0.001). Decrement rate of serum calcium during EDTA infusion was significantly lower (p less than 0.001) in hyperthyroid (-0.698 x 10(-3) +/- 0.12 x 10(-5)) than in normal control individuals (-1.486 x 10(-3) +/- 9.33 x 10(-5)), and went back to normal after treatment. EDTA-induced calcium lowering was sufficient to induce a PTH plateau of maximum response. Maximum PTH response in hyperthyroidism patients (2.34 +/- 0.45pmol) was significantly lower (p less than 0.001) than that observed in normal controls (7.51 +/- 0.40), PTH response was normal after six months of euthyroidism. CONCLUSIONS: bone mineral density showed a significant increment in treated patients, suggesting that these patients had suffered some degree of bone loss during the course of thyrotoxicosis. The lower PTH secretory reserve found in untreated hyperthyroid patients suggests that hyperthyroid state-induced bone loss may be a consequence of a direct action of thyroid hormones. This conditions was reverted after 6 months of euthyroidism. PMID- 1909455 TI - [Anti-BHc determination in blood donors in Sao Paulo: should this test be adopted in Brazil?]. AB - PURPOSE: to study the incidence of anti-HBc (core) as a surrogate marker for post transfusion Non-A, Non-B Hepatitis (HNANB-PT) among blood donors in Sao Paulo, Brazil. TYPE: prospective, screening all blood donors from September to December, 1989 (nr. 2,773 donors). PLACE: Sirio-Libanes Hospital and 9 de Julho Hospital (Sao Paulo). PATIENTS: a total of 2,773 donors, 84% male and 16% female. METHOD: the tests used were competitive ELISA for Anti-HBc. MEASUREMENTS AND RESULTS: the repeated rah reactivity (RR) was 10.2% among all donors, with a higher incidence in males than in females (10.9% x 6.8% p less than 0.05 6y X2). Only 4.5% were borderlines, and 94.5% showed an absorbance/cut-off ratio less than 0.9. CONCLUSIONS: despite the lack of prospective studies correlating HNANB-PT to surrogate markers (e.g. ALT and anti-HBc) in this country, the high incidence of anti-HBc in donors allows to conclude that it might be as high as reported in other countries. Although the costs related to the adoption of this test, its indication in other countries and its association with the newly-developed specific test (anti-HCV) supports the idea of anti-HBc as a screening test for HNANB-PT in Brazil, at least in the most developed blood centers in the country. PMID- 1909456 TI - Anti-HIV and anti-anti-MHC antibodies in alloimmune and autoimmune mice. AB - Alloimmune mice (mice that have been exposed to cells from another murine strain) were shown to make antibodies against gp120 and p24 of human immunodeficiency virus (HIV), and mice of the autoimmune strains MRL-lpr/lpr and MRL-(+)/+ made antibodies against gp120. This is surprising because the mice were not exposed to HIV. Furthermore, anti-anti-MHC antibodies (molecules that have shapes similar to those of major histocompatibility complex molecules) were detected in both alloimmune sera and MRL mice. These results are discussed in the context of a possible role for allogeneic stimuli in the pathogenesis of acquired immunodeficiency syndrome, as suggested by an idiotypic network model. PMID- 1909458 TI - Serologic diagnosis of acute and chronic viral hepatitis. PMID- 1909457 TI - Ca(2+)-induced Ca2+ release in sea urchin egg homogenates: modulation by cyclic ADP-ribose. AB - Calcium-induced calcium release (CICR) may function widely in calcium-mediated cell signaling, but has been most thoroughly characterized in muscle cells. In a homogenate of sea urchin eggs, which display transients in the intracellular free calcium concentration ([Ca2+]i) during fertilization and anaphase, addition of Ca2+ triggered CICR. Ca2+ release was also induced by the CICR modulators ryanodine and caffeine. Responses to both Ca2+ and CICR modulators (but not Ca2+ release mediated by inositol 1,4,5-trisphosphate) were inhibited by procaine and ruthenium red, inhibitors of CICR. Intact eggs also displayed transients of [Ca2+]i when microinjected with ryanodine. Cyclic ADP-ribose, a metabolite with potent Ca(2+)-releasing properties, appears to act by way of the CICR mechanism and may thus be an endogenous modulator of CICR. A CICR mechanism is present in these nonmuscle cells as is assumed in various models of intracellular Ca2+ wave propagation. PMID- 1909459 TI - Human pathogenic viruses and parasites: emerging pathogens in the water cycle. PMID- 1909460 TI - Dissemination of human pathogens by airline travel. PMID- 1909461 TI - The monitoring and detection of Bacillus anthracis in the environment. PMID- 1909463 TI - Cost-effectiveness studies in the treatment of schizophrenia: a review. PMID- 1909462 TI - Maternal tetanus immunization in Aceh Province, Sumatra: the cost-effectiveness of alternative strategies. AB - This paper compares the cost per completed maternal tetanus immunization and an estimate of the cost per death averted in the routine EPI program with similar results from an experimental mass campaign in Aceh Province, Indonesia. The cost effectiveness of the mass campaign in achieving complete immunization is similar to the routine program. However, the mass campaign is probably less cost effective in averting neonatal tetanus deaths, due to its broader targetting. Factors affecting efficiency, coverage, and financing of tetanus immunization programs are assessed. While expansion of the routine EPI program is the preferred goal, mass campaigns are judged to be a reasonable part of the multi year strategy for tetanus control in the province. Recent experiments with an accelerated routine program may provide further alternatives. PMID- 1909464 TI - [New-onset angina pectoris: clinical aspects, diagnosis, prognosis and treatment tactics]. AB - NOA patients are not a homogeneous population in relation to impairment of coronary circulation, clinical symptoms and prognosis. Early hospitalization and treatment of the disease result in more favourable hospital and long-term responses than in the overall population of coronary patients. Conservative and surgical treatment in them produce almost similar results as regards survival and incidence of acute myocardial infarction. Hence, it is thought justifiable to use drugs in the majority of NOA patients leaving surgery only for patients with grave multiple coronary lesions and resistance to chemotherapy. PMID- 1909465 TI - [Use of the preparation Ditek in chronic obstructive lung diseases]. PMID- 1909466 TI - [The therapeutic results and early and late toxicities of the treatment of anal canal carcinoma by radiotherapy or chemoradiotherapy]. AB - From 1975 to 1989 114 patients with anal canal carcinoma were treated, 81 of these with radiotherapy (RT) alone and 33 with chemoradiotherapy (CRT), 80% respectively 82% of the patients were colostomy-free at the onset of therapy. RT was given to a total dose of 60 Gy in six weeks, for CRT additional simultaneous 5-fluorouracil (500 mg/m2 days 1 to 5 and 8 to 12) and mitomycin C (5 mg/m2 days 5 and 12) was administered. 67% respectively 82% of the patients had UICC stage II to IIIB disease predominantly with G2 and G3 squamous cell carcinomas. Local control after three years was 79% for the RT group vs. 82% for the CRT group. Three-year survival rate was 68% and 71%, respectively. These differences were not significant. Only for G1- compared to G3-tumors there is a significantly higher survival rate. Acute and late damage was slightly lower for the RT treatment group (77% and 25%) compared to the CRT group (79% and 30%). In both treatment groups there was one patient needing a permanent colostomy due to radiation induced proctitis. In conclusion, RT or CRT should be the primary form of treatment in patients with and canal carcinoma and abdominoperineal resection should only be performed in case of local recurrence or tumor persistence. The final decision about the indications for RT or CRT can only be made with the results of a prospective randomized trial. PMID- 1909467 TI - [A comparative assessment of the efficacy of thiophosphamide electrophoresis and ultrasound in the combined therapy of reactive arthritis]. AB - The results of the treatment of patients suffering from rheumatoid arthritis with ultrasound (group I), thiophosphamide electrophoresis (group II), ultrasound and thiophosphamide (group III) and with medicamentous agents alone (group IV) are compared. The positive therapeutic effect was recorded in patients of all 4 groups, with that effect being most remarkable in group III. PMID- 1909468 TI - The acute phase response and vitamin A status in malaria. AB - Plasma retinol and 5 carotenes were assayed by high performance liquid chromatography in Thai rural and urban malaria patients and matched control subjects. Plasma retinol was lower in the rural than in the urban controls and both groups of malaria patients had lower serum retinol concentrations than their respective controls. 29% (6/21) of the rural patients were biochemically deficient in retinol (less than or equal to 0.35 mumol/litre), suggesting severely depleted liver stores of vitamin A. The carotene data suggest that the intake of total carotenoids may be 50 to 100% greater than in the UK and that a much higher proportion of dietary beta-carotene is converted to vitamin A than in British adults. The concentrations of non-pro-vitamin A carotenoids in both groups of malaria patients were not compatible with vitamin A deficiency. The differences between patient and control median concentrations of pro-vitamin A (PVA) carotenoids were greater than those of non-PVA carotenoids, suggesting increased utilization of vitamin A in malaria. There was no evidence of clinical vitamin A deficiency in either of the communities studied; therefore, severely depleted stores of retinol are very unlikely. There is an alternative explanation for low plasma retinol levels in malaria patients because retinol is bound to the negative acute phase proteins, retinol binding protein and transthyretin. We suggest that the behaviour of retinol during infection indicates a rapid distribution into extravascular fluids and an increased availability to the tissues; i.e., it may be another beneficial effect of the acute phase response. PMID- 1909469 TI - A randomized trial comparing a pentavalent antimonial drug and recombinant interferon-gamma in the local treatment of cutaneous leishmaniasis. AB - In a randomized prospective trial N-methyl-glucamine antimoniate (Glucantime) and human recombinant interferon-gamma were infiltrated around lesions of cutaneous leishmaniasis caused by Leishmania tropica in Syria. A previous trial had shown that intradermal application of interferon-gamma promoted the healing of similar lesions in the study area. Twenty patients with 38 lesions received 1-3 ml Glucantime and 20 patients with 37 lesions received 25 micrograms of interferon gamma intradermally once weekly for 5 consecutive weeks. While all lesions treated with Glucantime were free of parasites after the third injection, only 69% of those treated with interferon-gamma were parasitologically cured by week 10. Within 10 weeks, lesions treated with Glucantime healed completely in 29/38, and partially in 9/38, cases, whereas 1/37 and 13/37 lesions treated with interferon-gamma healed completely and partially, respectively. Perilesional application of Glucantime was highly effective and superior to interferon-gamma for treatment of cutaneous leishmaniasis caused by L. tropica. PMID- 1909470 TI - Coincidence of tissue antibody and cardiac pathology in mice infected with Trypanosoma cruzi. PMID- 1909471 TI - A field study of the effect of ivermectin on intestinal helminths in man. AB - A single stool specimen from each of 904 villagers participating in a placebo controlled trial of ivermectin for onchocerciasis was examined for intestinal helminths by the formol-ether technique. Ivermectin had a significant effect on Ascaris infection, reducing prevalence and intensity for at least 3 months, but rapid reinfection occurred. There was no significant effect on Trichuris, Necator or Schistosoma mansoni infections. Incidental Strongyloides infections were not seen commonly in this population, but were significantly reduced in the ivermectin-treated group. Regular administration of ivermectin on a mass basis would reduce the prevalence of Ascaris infection and any attendant morbidity. This is a useful additional effect of the drug. PMID- 1909473 TI - Hypogonadotropic hypogonadism and temporal lobe epilepsy. AB - The concomitant finding of hypogonadotropic hypogonadism and temporal lobe epilepsy raises the issue of whether or not these entities are related. The case presented herein is one such example. The possible pathophysiologic basis of infertility and temporal lobe epilepsy is reviewed. PMID- 1909472 TI - Effects of chondroitin sulphate, human serum albumin and Tamm-Horsfall mucoprotein on calcium oxalate crystallization in undiluted human urine. AB - The effects of physiological concentrations of chondroitin sulphate, human serum albumin and Tamm-Horsfall mucoprotein on the crystallization of calcium oxalate in undiluted, ultrafiltered human urine were investigated using particle size analysis and scanning electron microscopy. Neither the amount of oxalate required to induce detectable calcium oxalate crystal nucleation nor crystal morphology was affected by the presence of any of these macromolecules. Chondroitin sulphate had no effect on the amount of crystalline material deposited or on the size of the particles precipitated in response to a standard oxalate load. Human serum albumin slightly reduced the size of the crystal aggregates and caused a small increase in the amount of crystal matter precipitated. By contrast, Tamm-Horsfall mucoprotein significantly inhibited crystal aggregation and markedly increased the volume of matter deposited, although this could not be attributed to a promotion of solute precipitation. It was concluded that chondroitin sulphate, human serum albumin and Tamm-Horsfall mucoprotein cannot account for the inhibitory effects of macromolecules with a relative mass greater than 10 kDa in spun and filtered urine. Nonetheless, Tamm-Horsfall mucoprotein is likely to inhibit crystal aggregation in whole urine in vivo and may therefore be instrumental in preventing calcium oxalate stone formation. PMID- 1909474 TI - Mannitol-induced diuretic renal ultrasonography: a new technique. AB - We herein describe a new technique to improve the ultrasonic imaging of nonobstructed stone-bearing kidneys. Mannitol-induced diuresis opens up the collapsed renal collecting system and yields better ultrasonographic imaging by increasing the amount of fluid surrounding the calculi. The potential usages of this technique include ultrasound localization for percutaneous stone extraction and during ultrasonographic monitoring of stones treated by extracorporeal shock wave lithotripsy (ESWL). PMID- 1909475 TI - Bacteriologically stressed animal model of new closed catheter drainage system with microbicidal outlet tube. AB - We have used a catheterized rabbit model to test a newly developed catheter drainage system that incorporates a microbicidal outlet tube. In these tests, this new system was compared with a currently marketed closed drainage system, with daily challenge at the outlet tube using an auxotrophically marked uropathogenic strain of Escherichia coli. In the control series (silicone catheter connected to a standard drainage bag via a tamper-evidence seal) the challenge organism developed upstream biofilm colonization of the luminal surfaces of the catheter and drainage system that was complete in 4.6 +/- 2.1 days in 11 animals, while in 1 animal a rapid overgrowth of the system with Streptococcus faecalis developed. The presence of organisms other than the marked E. coli strain on the luminal surfaces of these control catheters showed that down stream colonization was also operative. In the test catheter drainage series, the microbicidal outlet tube insert precluded upstream colonization by the challenge organism in 12 of 16 catheters and significantly delayed (7.2 +/- 1.0 days) this colonization in the remaining 4 animals. When upstream colonization by exogenous bacteria was precluded by this effective device, downstream colonization of the drainage system by mixed populations of bacteria that probably migrated into the bladder via the extraluminal urethral route developed in some animals (6 of 16). PMID- 1909476 TI - Natural scrapie: detection of fibrils in extracts from the central nervous system of sheep. AB - Extracts from the cervical spinal cord and from the medulla, thalamus, cerebellum and cerebral cortex of the brains of 10 sheep, histopathologically confirmed as cases of scrapie, were examined by electron microscopy for the presence of scrapie-associated fibrils. Characteristic fibrils were observed in all the extracts except for that from the thalamus of one sheep. No fibrils were found in any extracts from three control sheep. A comparison of these results with a similar study of 22 cases of bovine spongiform encephalopathy (BSE) suggests that in cases of scrapie the area of the brain chosen for the detection of fibrils is less critical than in cases of BSE, in which fibrils are more readily extracted from areas of the brain stem. PMID- 1909477 TI - Contagious pustular dermatitis (orf) infection in sheep and goats in Saudi Arabia. PMID- 1909478 TI - 'Blue ear' disease of pigs. PMID- 1909479 TI - Eradication of East Coast fever. PMID- 1909480 TI - Purification and characterization of human immunodeficiency virus type 1 nef gene product expressed by a recombinant baculovirus. AB - We have constructed the recombinant baculovirus which expresses the human immunodeficiency virus type 1 negative factor (nef) gene. Spodoptera frugiperda cells infected with the recombinant virus produced a 27-kDa protein which reacted with rabbit antisera raised against a carboxy-terminal synthetic peptide of the Nef protein by immunoblot analysis. Labeling experiment showed that the recombinant Nef protein was myristoylated. The recombinant Nef protein was purified to near homogeneity by DEAE-Sephacel, phenyl-Sepharose 4B, blue Sepharose, and Sephadex G-150 column chromatography. No detectable GTP binding activity was observed in the purified recombinant Nef product. PMID- 1909481 TI - [Assessment of cost effectiveness of radical treatment of patients with pulmonary cancer]. AB - Cost-effectiveness of diagnostic and treatment procedures was assessed in 101 able-bodied patients with lung cancer who had undergone radical surgery. Those procedures proved cost-effective in cases of early stage tumor only since pulmonologic commissions assured shorter period of examination and good results were obtained by occupational rehabilitation. PMID- 1909482 TI - They seem to glide. Are there aerodynamic effects in leaping prosimian primates? AB - Leaping primates often assume a horizontal position while airborne. When the limbs are spread out in such maneuvers, skin folds between the upper limbs and the trunk are exposed. This has led to the assumption that the animals make use of aerodynamic forces for either gliding, steering, or braking before the landing. In terms of physics, aerodynamic lift or aerodynamic drag can cause the described effects. As coefficients of lift and drag are unknown for flying primates, we have calculated those values that give the animals either a 5% gain or loss in leaping distance. These turn out to be in the range of values for cylinder-shaped "blunt" (unstreamlined) bodies. A significant influence of aerodynamic forces on the flight path can therefore be assumed. The smaller bodied species (e.g., galagos) are more strongly influenced by their great surface areas. Although frontal areas scale positively allometrically with respect to body mass, air speed gains importance in the larger-bodied species (e.g., sifakas). They cover absolutely greater distances and have the higher takeoff velocities. The actual importance of lift and drag cannot be derived from our theoretical calculations but must be determined experimentally. PMID- 1909483 TI - [The optimization of the batch cultivation process for Pseudomonas aeruginosa to produce exotoxin A]. AB - The experimental study of conditions for the optimization of the batch cultivation of P. aeruginosa has been made. As revealed in this study the aim of this cultivation can be achieved by using exponentially growing culture in a dose of 1.10(9) cells/ml as seed material and by ensuring the conditions of rational air supply during the main cultivation process. PMID- 1909484 TI - [The role of soft tissues in downward stability of the glenohumeral joint--an experimental study with fresh cadavers]. AB - Inferior stabilizing mechanism was studied after anatomical dissection of vertical stabilizing tissues in 98 fresh shoulder joints from human autopsies and measuring relative restraint by stabilizing tissues in 8 fresh shoulder specimens from monkeys. This results demonstrated that the coracohumeral ligament and supraspinatus tendon were most important structure as static and dynamic stabilizers, and closely interacted with each other in preventing inferior subluxation of the glenohumeral joint. PMID- 1909485 TI - Lisuride plus selegiline in the treatment of early Parkinson's disease. AB - We treated 20 early Parkinson's disease subjects with the dopamine agonist lisuride in combination with the MAO-B inhibitor selegiline (L-deprenyl). We started with lisuride alone for one month, then we added selegiline versus placebo to lisuride in double-blind conditions for 3 months; finally all patients received lisuride and selegiline for another 3 months. Lisuride alone (1.43 +/- 0.10 mg) significantly improved PD. When selegiline (10 mg/day) was added in the double-blind phase the mean lisuride dosage could be reduced by 22.8% without deterioration of the clinical effects, and the same occurred in the former placebo group when selegiline was added. The combination of both drugs was well tolerated. These data are of interest for the interpretation of the effects of selegiline. PMID- 1909486 TI - Secretory antibodies specific to Streptococcus pneumoniae, Haemophilus influenzae and Branhamella catarrhalis in middle ear effusion during acute otitis media. AB - The occurrence of specific secretory antibodies against the type-specific capsular polysaccharide of Streptococcus pneumoniae (Pn) and against the whole cell antigen of Haemophilus influenzae (Hi) and Branhamella catarrhalis (Br) were measured by the ELISA method in 211 middle ear effusion (MEE) samples of 85 children with acute otitis media (AOM) during the course of the disease. Antibodies against at least one of those bacteria were detected at the initial visit in 33.6% of the ears and later in 20%. All in all, such antibodies could be found in 50% of the ears during the follow-up. Pneumococcal secretory antibodies were found in 5 out of 116 ears only, anti-Hi antibodies in 52 and anti-Br antibodies in 42 ears. The specific secretory antibodies were detected against all these bacteria regardless of the bacterial etiology of the AOM attack in question. The AOM attack was prolonged more often if such antibodies were not found in the MEE sample taken at the initial visit. The appearance of such antibodies during the disease seemed to imply termination of the AOM episode in question. The conclusions of this study are that during an AOM attack a local production of antibodies in middle ear against the three most common bacteria. Pn, Hi and/or Br, causing AOM may be induced. The appearance of such antibodies in MEE seems to be beneficial for the resolution of AOM. PMID- 1909487 TI - Nasopharyngeal flora in otitis media with effusion. A comparative semiquantitative analysis. AB - An inflammatory process in the middle ear caused by bacteria or bacterial products emanating from the nasopharynx is one etiological factor considered in the unknown pathogenesis of otitis media with effusion (OME). The nasopharyngeal prevalence of Streptococcus pneumoniae, Haemophilus influenzae, Moraxella (Branhamella) catarrhalis and Streptococcus pyogenes was studied in 191 children with defined OME and in 53 age-matched children without middle ear disease. Duplicate sampling and semiquantitative analysis were performed to assess even minor differences in the distribution of pathogens between the two groups of children. Pathogens were recovered in 91% of OME children. A significantly higher number of pathogen species/patient (1.66 vs. 1.15, p less than 0.01) as well as pathogen colonies/patient was found in OME children compared to control children. Chronic OME in children is associated with an increased pathogen load in the nasopharynx, suggesting a role of these pathogens in the etiology of OME. PMID- 1909488 TI - In vivo attachment of beta-haemolytic streptococci to tonsillar epithelial cells in health and disease. AB - In vivo attachment of beta-haemolytic streptococci Group A (GABHS) to the epithelial cells of the palatine tonsils was determined in 10 patients with current acute tonsillitis (AT-group) and in 10 healthy carriers of GABHS (C group) according to a method described. Standard bacterial culture revealed growth of GABHS in both groups. In the AT-group, massive attachment of streptococcal chains to the tonsillar epithelium was noted. These chains proved positive for FITC-labelled antibodies against beta-haemolytic streptococci, and were only occasionally found in the C-group. The overall bacterial attachment was significantly greater in the AT-group than in the C-group (p less than 0.001). Phenoxymethylpenicillin treatment caused a dramatic decrease in the number of the attached GABHS bacteria within 24 h. Two weeks after completion of the penicillin treatment one individual in each group was still culture-positive for GABHS. PMID- 1909489 TI - [Determination of thiocarbamide and related derivatives using an S-alkylation reaction]. AB - S-alkylation reaction based on the Hantzsch synthesis followed by cyclization and aromatization reactions were used to develop an analytical procedure. The various thiocarbamide derivatives were transformed to substituted aminothiazol by using suitable alpha-halogenoketones as the reagents. At the end of the reaction the reaction products are present as 2-aminothiazol salts. The acidimetric determination of the latter can easily be performed using acetone or methanol as the solvents and 0.1 M sodium hydroxide as the titrant. The forming 2 aminothizols with their different basicities are characteristic of the parent thiocarbamide derivatives. On the basis of the different basicities their simultaneous determination is possible and the shape of the titration curves enables the thiocarbamides to be characterized and identified. PMID- 1909490 TI - 46,XX gonadal dysgenesis with epibulbar dermoid. AB - Pure gonadal dysgenesis with 46,XX genotype is a rare abnormality with unknown etiology. Although sensorineural deafness has been described with 46,XX gonadal dysgenesis, the majority of reported cases of 46,XX gonadal dysgenesis have no associated physical abnormalities. We report a patient with 46,XX gonadal dysgenesis associated with epibulbar dermoids and preauricular skin tags, the classic ocular and skin manifestations of Goldenhar sequence (oculoauricular vertebral dysplasia). We propose that our patient may represent a new and previously unreported syndrome. PMID- 1909491 TI - Molecular analysis of a patient with neurofibromatosis 1 and achondroplasia. AB - The gene for von Recklinghausen neurofibromatosis (NF1) is on proximal 17q; the location of the gene for achondroplasia (ACH) is unknown. We have begun a molecular analysis of a patient with mental retardation, NF1 and ACH, a clinical presentation suggestive of a contiguous gene syndrome. In addition, this individual has a 47,XYY chromosome constitution. To define a possible chromosome 17 deletion, we investigated the copy number of DNA sequences linked to NF1 with conventional and pulsed-field gel electrophoresis (PFGE). We found no evidence for a deletion on chromosome 17. These results make it unlikely that this patient harbors a single deletion in the NF1 region causing both NF1 and ACH and suggest different mechanisms for the de novo occurrence of 2 autosomal dominant disorders in this individual. PMID- 1909493 TI - Kinetic superiority of intra- vs. extracellular pentose pathway flux: studies in porous adipocytes. AB - Considering how the cytosol is typically prepared, to wit, by cell disruption and ultracentrifugation, historically this compartment has been deemed unstructured and kinetically analogous to a solubilized system. By prudently permeabilizing rat adipocytes so that there is scant enzyme egress, intermediary metabolism can be explored intracellularly. Herein, cytoplasmic flux vs. a soluble reference system was compared. The three-enzyme oxidative portion of the pentose pathway was examined using [1-14C]glucose 6-phosphate (G-6-P); both the steady-state velocities (nu o) and transient times (tau ss) were compared in each system. At low G-6-P levels (much less than km), nu o is dependent solely on the activity of the first enzyme, and tau ss is determined by the distal two enzymes. In our experiments, the need also arose to compare tau ss between preparations, wherein the enzyme concentrations were unequal. It is shown that tau ss.nu o/G-6-P serves as an index of kinetic efficiency. Over various dilutions, the kinetic value (nu o/G-6-P) for the porous cells ranged from 2.0 to 23.9 x 10(-6) l/min, with corresponding tau ss values of 18-1.0 min. The respective values for the solubilized enzyme system were from 4.9 to 42.2 x 10(-6) l/min and from 15.2 to 1.1 min. This abbreviated pathway occurring in porous cells was nearly twice as fast at reaching steady state than the corresponding solubilized system. We conclude that cytoplasmic flux is kinetically efficient and that metabolic studies conducted only under Vmax conditions and ignoring tau ss could overlook the cellular effects of hormones or pathological states. PMID- 1909492 TI - Sequestration of tau by granulovacuolar degeneration in Alzheimer's disease. AB - Antibodies directed against three regions of tau have been used in a histologic study of granulovacuolar degeneration (GVD) in Alzheimer's disease (AD). Granulovascular degeneration complexes, consisting of a dense granule in a less dense vacuole, were found in hippocampal pyramidal neurons in all patients studied. Anti-tau antibodies directed against the N-and C-termini, and the repeat region of tau, were found to immunolabel the granule of the GVD complex. Intracellular neurofibrillary tangles also were labeled by these antibodies. In particular, MAb6.423, which recognizes tau protein sequestered in paired helical filaments (PHF) in AD, but not the normal tau proteins so far described in human brain, labeled GVD granules. Contrarily, a generic tau marker (MAb7.51), which immunolabels all known isoforms of isolated and expressed tau protein, including PHF-tau, did not label the GVD granule. These findings demonstrate that the entire tau molecule is sequestered within the GVD granule, and that the tau protein found in GVD complexes is antigenically related to that found in PHFs. There is, however, a difference in the way in which the repeat region of tau is incorporated into the two structures, making the MAb7.51 epitope unavailable in the GVD complex. These findings suggest that the formation of GVD complexes in hippocampal pyramidal neurons vulnerable to neurofibrillary degeneration may represent an alternative pathway for dealing with an aberrant molecular complex, which contributes to the formation of GVD granules and neurofibrillary tangles in AD. PMID- 1909494 TI - Cis-inhibition and trans-stimulation of cationic amino acid transport in the perfused rat pancreas. AB - Transport of cationic amino acids in the isolated perfused rat pancreas was studied using dual-isotope dilution techniques. At 50 microM substrate concentration, unidirectional tracer uptakes for L-arginine (56 +/- 1%), L-lysine (49 +/- 2%), and L-ornithine (44 +/- 3%) were followed by rapid tracer efflux. In the presence of Na+, influx of L-arginine [Michaelis constant (Km) = 1.74 +/- 0.15 mM, maximum velocity (Vmax) = 1.97 +/- 0.07 mumol.min-1.g-1] and L-lysine (Km = 2.48 +/- 0.17 mM, Vmax = 2.42 +/- 0.08 mumol.min-1.g-1) was mediated by a common transport system, sensitive to cis-inhibition by L-ornithine, 2,4-L diaminobutyric acid, D-lysine, and D-arginine. Substrates for system A [alpha (methylamino)isobutyric acid] and an anionic carrier (L-aspartate) were poor cis inhibitors of L-arginine entry. Removal of Na+ resulted in a 40% reduction in cationic amino acid influx. After cell loading (20 min), L-[3H]-lysine cleared predominantly from a slowly exchanging pool with a rate constant of 5.97 +/- 0.67 min. An influx/efflux permeability ratio of 14.5 +/- 1.6 was determined, and efflux of L-lysine was trans-stimulated by vascular challenges with cationic or large neutral amino acids. The specificity, relative Na+ independence, and exchange properties of this saturable cationic amino acid transporter in the pancreatic epithelium resemble those reported for system y+ in cultured fibroblasts and hepatocytes. PMID- 1909495 TI - Energy expenditure by doubly labeled water: validation in lean and obese subjects. AB - The doubly labeled water (2H2(18)O) method to assess energy expenditure in free living conditions has been successfully validated against gas exchange measurements in lean healthy volunteers in both sedentary conditions and during sustained heavy exercise. However, no data are available on obese subjects. We therefore compared the 2H2(18)O method with indirect calorimetry (respiratory chamber) in 12 male subjects covering a wide range of body weight and composition (61-190 kg, 7-41% fat). Isotope pool sizes and elimination rates were calculated from 18O and 2H enrichments in baseline urine samples and in 7-h, 11.5-h, and daily postdose urine samples using the multipoint slope/intercept method. Results were corrected for isotopic fractionation. Mean 7-day energy expenditure in the respiratory chamber varied from 1,851 to 4,105 kcal/day. The doubly labeled water method tended to underestimate energy expenditure (-2.5 +/- 5.8%, not equal to 0, range -14 to +4%), with the larger underestimate observed in heavier and fatter subjects (r = -0.82 and -0.68, P less than 0.02, respectively). The underestimation in heavier subjects might be related to larger sequestration of deuterium during fat synthesis. In conclusion, the doubly labeled water method is a suitable and accurate method to measure energy expenditure in free-living conditions but might provide a slightly underestimated figure in fatter subjects. PMID- 1909496 TI - Radiation exposure from long-lived beta emitters in clinical investigation. AB - Potential hazards restrict the use of 14C in clinical investigation. Nevertheless, 14C, in readily metabolized compounds, continues to be administered and in relatively large doses. The compounds are converted to intermediates and products with longer half-lives than their half-lives. These longer biological half-lives have not always been taken into account, although calculations of radiation exposure can be markedly altered by their inclusion. The minimum dose of 14C needed to accomplish a study must also be considered, and benefits relative to risks in the administration must be assessed in terms of the kind and total number of subjects required. Similar considerations apply to the administration of 3H-labeled compounds. Furthermore, in assessing risks, the limited information available on the localization and concentration of the isotopes in the body should be taken into account. There are also concerns with regard to administrations in growth situations and to an individual on multiple occasions. Within those constraints, 14C and 3H can be given with relative safety. PMID- 1909497 TI - Release of arachidonic acid by complement C5b-9 complex in glomerular epithelial cells. AB - In experimental membranous nephropathy, C5b-9 induces noncytolytic glomerular epithelial cell (GEC) injury and proteinuria, which in some models is partially mediated by metabolites of arachidonic acid. In cultured GEC, sublytic C5b-9 increases cytosolic Ca2+ concentration ([Ca2+]i), activates phospholipase C (PLC), and releases arachidonic acid and eicosanoids. This study examined mechanisms of arachidonic acid production by C5b-9. In GEC labeled with [3H]arachidonate C5b-9 increased free [3H]arachidonic acid and 1,2-[3H] arachidonoyl-diacylglycerol (DAG), an endogenous activator of protein kinase C (PKC). Elevated [Ca2+]i was not sufficient to account for increased free arachidonic acid. Moreover, in GEC that had been depleted of PKC by preincubation for 18 h with 2 microM phorbol myristate acetate, the C5b-9-induced arachidonate release was inhibited by greater than 75%. Reacylation of phospholipids was not decreased by C5b-9. Homogenates of GEC that had been stimulated with C5b-9 released more [14C]arachidonate from exogenously added 2-[14C]arachidonoyl phosphatidyl-ethanolamine or 2-[14C]arachidonoyl-phosphatidylcholine than homogenates of unstimulated cells (assayed at a Ca2+ concentration of 2 mM). These experiments demonstrate directly that C5b-9 increased phospholipase A2 (PLA2) activity. PLA2 appeared to be stimulated as a result of PKC activation (probably secondary to increased DAG) in association with elevated [Ca2+]i. The C5b-9-induced activation of PLA2 may lead to release of eicosanoids, which may contribute toward impaired glomerular capillary wall permselectivity in experimental membranous nephropathy. PMID- 1909498 TI - Effect of thiazides on colonic NaCl absorption: role of carbonic anhydrase. AB - The mechanisms by which the benzothiadiazide class of diuretics inhibit electroneutral NaCl absorption are not fully understood. We studied the mechanisms of thiazide action in perfused loops of distal colon in anesthetized male Sprague-Dawley rats. Hydroflumethiazide (1 mM) reversibly inhibited greater than 40% of Na, Cl, and water absorption. Prior exposure of the colon to the carbonic anhydrase inhibitor methazolamide (0.1 mM) prevented the effects of hydroflumethiazide and metolazone, a thiazide-like drug, on colonic absorption. In Ussing flux chambers, addition of hydroflumethiazide to both the mucosal and serosal bathing solutions (but not to the mucosal solution alone) caused marked decreases in Na and Cl absorption. Such inhibition only occurred at concentrations of hydroflumethiazide (0.1 and 1.0 mM) that inhibited greater than 90% of carbonic anhydrase activity in homogenized colonic mucosa. We conclude that an important mechanism by which thiazides inhibit NaCl absorption in the rat distal colon is by inhibition of mucosal carbonic anhydrase. In tissues containing this enzyme, this mechanism of thiazide effect on ion flux must be considered. PMID- 1909499 TI - Effect of local pH on interstitial fluid pressure. AB - It has been suggested that electrostatic interactions between the electric charges on the interstitial gel matrix play a significant role in determining tissue elasticity and interstitial fluid pressure (IFP). The relationship between the net charge and IFP, however, has not been adequately established. Our purpose was to explore the net electric charge-IFP relationship, and in vivo experiments were performed to test its validity. IFP was measured in the subcutaneous tissue of anesthetized rats with the chronically implanted capsule method, and the acid base status in blood and interstitial fluid was monitored. The net charge, which can be varied by pH, was altered by electrolysis procedure. H+ and OH- generated inside the capsule caused transient and dose-dependent IFP responses. The curve, describing the relationship between capsular pressure changes and amount of generated H+ and OH-, has a maximum at zero net charge, and the excess electric charge, either positive or negative, results in a significant decrease in capsular pressure in accordance with the hypothesis. The time course, as well as the dose dependency, of IFP suggests that the subcutaneous tissue gel in control condition has slightly positive net charge. PMID- 1909500 TI - Modulation by extracellular pH of bradykinin-evoked activation of Ca(2+) activated K+ channels in endothelial cells. AB - We used the patch-clamp technique to investigate, via the activation of Ca(2+) activated potassium channels [K(Ca2+)channels], the effects of extracellular pH (pHo) on the bradykinin (BK)-stimulated rise in cytosolic Ca2+ concentration in bovine aortic endothelial cells (BAE). In cell-attached experiments, the external application of BK caused a transient activation of the K(Ca2+) channels. Increasing pHo from 7.3 to 9 maintained the channel activity, which was not inhibited by withdrawing the agonist. The channel-activation process could be blocked either by removing external Ca2+ or by depolarizing the cells with a high K+ external solution. These results indicate that the Ca2+ influx triggered by BK contributes in maintaining the agonist-evoked response in high pHo. Changes in pHo produced a slight increase in the intracellular pH (pHi) measured fluorimetrically with the H+ indicator dye 2',7-bis(carboxyethyl)5(6') carboxyfluorescein. However, increasing pHi by the external application of NH4Cl at physiological pHo caused a rapid decline and not an increase in the K(Ca2+) channel activity triggered by BK. In fura-2-loaded cells, alkaline pHo had no effect on the time course of the Ca2+ response to BK in external Ca(2+)-free conditions, suggesting that the Ca2+ extrusion process is not affected by pHo. Our results suggest that the BK-evoked Ca2+ influx, which is required to reload internal Ca2+ stores, is controlled by a mechanism depending on extracellular H+. PMID- 1909501 TI - Activation of cardiac ATP-sensitive K+ current during hypoxia: correlation with tissue ATP levels. AB - Although previous work has implicated activation of ATP-sensitive K+ currents (IK,ATP) in action potential duration (APD) shortening and increased cellular K+ efflux during hypoxia, ischemia, and metabolic inhibition, no prior study has directly assessed the tissue levels of ATP at which IK,ATP activates in intact cardiac muscle. Accordingly, we correlated changes in tissue high-energy phosphate levels during substrate-free hypoxia with activation of IK,ATP in intact voltage-clamped rabbit papillary muscles. During 10 min of hypoxia, the outward K+ current measured in response to a voltage-clamp pulse step from -50 to 0 mV increased from 8.57 +/- 0.27 to 15.67 +/- 1.41 microA (P less than 0.05, n = 6), and APD decreased from 452 +/- 54 to 292 +/- 56 ms (P less than 0.05, n = 6). Glibenclamide (10 microM), a specific IK,ATP blocker, prevented both of these changes. In a parallel set of experiments, papillary muscles were freeze-clamped and assayed for tissue ATP. In these muscles, 10 min of hypoxia resulted in a comparable degree of APD shortening (441 +/- 24 to 297 +/- 18 ms, P less than 0.05, n = 12), and tissue ATP levels fell from 13.2 +/- 1.3 to 9.7 +/- 0.7 mumol/g dry wt (P less than 0.05, n = 12). These results directly demonstrate that IK,ATP is activated and causes APD shortening during hypoxia in intact cardiac muscle despite only a modest (approximately 25%) decline in tissue ATP content. PMID- 1909502 TI - Cytochrome P-450-dependent vasodilation of rat kidney by arachidonic acid. AB - Our previous studies indicated a role for cytochrome P-450-dependent enzymes in generating the mediators of the vasodilator effect of arachidonic acid (AA) in the preconstricted indomethacin-treated perfused kidney of the rat. We report that in vivo induction of cytochrome P-450 enzymes with 3-methylcholanthrene-beta naphthoflavone or dexamethasone enhanced the renal vasodilator effect of AA in this experimental preparation. Conversely, depletion of cytochrome P-450 enzymes with stannous chloride or cobalt chloride diminished the vasodilator response to AA. Injection of AA resulted in the release of relaxant material into the renal effluent detected by superfusion of rabbit aortic rings. Inhibition of cytochrome P-450 with 7-ethoxyresorufin reduced the release of vasorelaxant material. Metabolism of labeled AA by the kidney revealed four peaks of radioactivity that were recovered from the renal effluent. The heights of these peaks were reduced by 7-ethoxyresorufin. These results provide further evidence for cytochrome P-450 dependent metabolism of AA to one or more vasodilator products by the rat kidney. PMID- 1909503 TI - Glibenclamide attenuates adenosine-induced bradycardia and coronary vasodilatation. AB - The effects of the ATP-sensitive K(+)-channel blocker glibenclamide on the cardiovascular responses to adenosine in dogs were determined. Adenosine (0.01-20 mumol/kg iv) caused coronary vasodilatation, arterial hypotension, and bradycardia in dogs with either combined beta-adrenergic and muscarinic receptor blockade or with bilateral cervical vagotomy plus beta-adrenergic receptor blockade. The 50% effective dose for adenosine-induced coronary dilatation was increased from 0.13 +/- 0.04 mumol/kg in the control state to 1.1 +/- 0.5 mumol/kg after 2 mg/kg of glibenclamide (P less than 0.001). Adenosine at 5 mumol/kg reduced heart rate by 19 +/- 5% from a baseline of 158 +/- 6 beats/min in five anesthetized dogs. After glibenclamide (10 mg/kg), this dose of adenosine failed to cause a significant change in heart rate. The arterial hypotensive effects of adenosine were also attenuated by glibenclamide. Thus glibenclamide inhibited adenosine-induced bradycardia, hypotension, and coronary dilatation. On the other hand, glibenclamide did not affect the reductions in heart rate caused by vagus nerve stimulation. The mechanism of this adenosine antagonism is not known but, in the case of bradycardia, it does not appear to involve any of the steps shared in common by both adenosine-induced and vagal responses of the sinoatrial node. PMID- 1909504 TI - Hypothermic cerebral reperfusion and recovery from ischemia. AB - The effect of transient postischemic hypothermia (30 degrees C) on recovery of cerebral blood flow (CBF), oxygen consumption (CMRO2) and somatosensory-evoked potentials (SEPs) was determined in anesthetized dogs. Ischemia was produced for 20 min by intracranial pressure (ICP) elevation while core temperature was lowered by cooling externalized blood. Epidural temperature was controlled at 37.6 +/- 0.2 degrees C during ischemia, lowered to 30.0 +/- 0.1 degrees C during the first hour of reperfusion, and then rewarmed to 38.0 +/- 0.1 degrees C in experimental dogs (n = 8) and maintained at 38.0 +/- 0.1 degrees C in control dogs (n = 8). ICP was lower throughout reperfusion in experimental as compared with control animals. By 240 min of reperfusion, CBF was approximately 70% of control in both groups. CMRO2 was 60% of preischemic values in control animals and 74% in experimental animals (P = 0.077). A persistent uncoupling of CBF and CMRO2 was observed throughout reperfusion only in the control group. Recovery of SEP amplitude was significantly improved in the experimental group (26 vs. 11% of preischemic values). These data suggest that transient hypothermia reduces ICP and facilitates recovery of electrophysiological function after cerebral ischemia. PMID- 1909505 TI - Bicarbonate conservation during incomplete cerebral ischemia with superimposed hypercapnia. AB - We superimposed extreme hypercapnia (arterial Pco2 400-450 mmHg) immediately before and during incomplete cerebral ischemia to distinguish the role of intracellular pH (pHi) and bicarbonate [( HCO3-]i) in postischemic metabolic and electrophysiological recovery. Incomplete global ischemia was produced in seven anesthetized dogs by 30 min of intracranial hypertension followed by 4 h of reperfusion. ATP, phosphocreatine (PCr), and pHi were measured with 31P magnetic resonance spectroscopy, and [HCO3-]i was calculated from the Henderson Hasselbalch equation using the measured pHi and sagittal sinus Pco2. Cerebral blood flow was reduced to 7 +/- 1 ml.min-1.100 g-1 (+/- SE) during ischemia with extreme hypercapnia, and pHi decreased to 5.72 +/- 0.09. During normocapnic reperfusion, pHi rapidly returned to near baseline values by 14 min. [HCO3-]i fell from 12.1 +/- 0.9 to 6.0 +/- 1.2 mM by the midpoint of ischemia and recovered by 30 min of reperfusion. ATP, PCr, and O2 consumption also recovered rapidly and completely. Somatosensory-evoked potentials (SEP) recovered to 43 +/- 10% of control amplitude. These results are in marked contrast to the poor metabolic and SEP recovery previously observed in hyperglycemic dogs in which pHi decreased to the same range as with hypercapnic ischemia, but in which [HCO3-]i was much lower (1.1 +/- 0.5 mM). Therefore, [HCO3-]i depletion during hyperglycemic ischemia may be a more important factor in recovery than end ischemic pHi per se. We speculate that higher [HCO3-]i may improve glial cell buffering capacity or decrease iron availability for hydroxyl radical production. PMID- 1909506 TI - The effects of intravenous clonidine on ventilation. AB - The effects of clonidine, an alpha 2 adrenergic agonist, on ventilation were studied in a group of adult volunteers. The ventilatory variables measured were minute ventilation, respiratory rate, end-tidal carbon dioxide tension and the response to carbon dioxide challenge. We found no differences in minute ventilation, respiratory rate and end-tidal carbon dioxide tension, before and after clonidine administration. However, the ventilatory response to carbon dioxide was significantly attenuated following clonidine, suggesting that clonidine has respiratory depressant effects. PMID- 1909507 TI - The separation of chondroitin sulfate disaccharides and hyaluronan oligosaccharides by capillary zone electrophoresis. AB - We have developed techniques for the separation of unsulfated (2-acetamido-2 deoxy-3-O-(4-deoxy-alpha-L-threo- hex-4-enopyranosyluronicacid)-D-galactose and D-glucose), monosulfated (2-acetamido-2-deoxy-3- O-(4-deoxy-2-O-sulfo-alpha-L threo-hex-4-enopyranosyluronic acid)-D-galactose and 2-acetamido-2-deoxy-3-O-(4 deoxy-alpha-L-threo-hex- 4-enopyranosyluronic acid)-4-sulfo-D-galactose and -6 sulfo-D-galactose),disulfated (2-acetamido-2-deoxy-3-O-(4-deoxy-2-O-sulfo-alpha-L threo-hex-4- enopyranosyluronic acid)-4-sulfo-D-galactose and -6-sulfo-D galactose and 2-acet-amido-2-deoxy-3-O-(4-deoxy-alpha-L-threo-hex-4-enopy- ranosyluronic acid)-4,6-di-O-sulfo-D-galactose), and trisulfated (2-acetamido-2 deoxy-3-O-(4-deoxy-2-O- sulfo-alpha-L-threo-hex-4-enopyranosyluronic acid)-4,6-di O-sulfo-D-galactose) isomers of chondroitin using capillary zone electrophoresis. In addition, it is possible to separate oligomers of hyaluronan by similar protocols. These techniques represent a rapid, sensitive, and reproducible technique for the assay of these molecules from digests of connective tissues. PMID- 1909508 TI - Capillary electrophoresis for the analysis of chondroitin sulfate- and dermatan sulfate-derived disaccharides. AB - High-voltage capillary zone electrophoresis (CZE) has been used for the first time in the analysis of non-, mono-, di-, and trisulfated disaccharides derived from chondroitin sulfate, dermatan sulfate, and hyaluronic acid. These glycosaminoglycans are first depolymerized using polysaccharide lyases. The resulting unsaturated disaccharide products can be detected by their ultraviolet absorbance at 232 nm. Different retention times were obtained for each unsaturated disaccharide analyzed by CZE. The application of a constant voltage across a 70-cm fused silica capillary using a single, simple buffer system resolved an eight-component mixture within 40 min. Quantitation of disaccharides derived from chondroitin sulfate using chondroitin ABC lyase (EC 4.2.2.4) and mixtures of unsaturated disaccharide standards was possible requiring only picogram quantities of sample. The disaccharides examined had a net charge of from -1 to -4 and were resolved primarily on the basis of net charge and secondarily on the basis of charge distribution. Two unsulfated disaccharides both containing the same unsaturated uronic acid residue were analyzed. One was from chondroitin having an N-acetylgalactosyl residue and one from hyaluronate having an N-acetylglycosyl residue. Despite the fact that they differed only by the chirality at one center, these disaccharides were resolved by CZE. CZE is a fast and simple method that represents a powerful new tool for analysis and separation of acidic disaccharide components of glycosaminoglycans. PMID- 1909509 TI - Analytical procedures for a cryptic messenger RNA that mediates translational control of prostaglandin synthase by glucocorticoids. AB - Expression of the enzyme prostaglandin H synthase in cultured vascular smooth muscle cells required epidermal growth factor (EGF) and type beta transforming growth factor (TGF-beta) and was inhibited by cycloheximide but not actinomycin D. Preincubation with the glucocorticoid dexamethasone (0.5 microM) blocked the EGF-induced expression of prostaglandin H (PGH) synthase. Following dexamethasone addition, levels of hybridizable mRNA for PG synthase were reduced by over 90% within 1 h. After dexamethasone was removed, PG synthase mRNA recovered within 3 h by a process that was not inhibited by actinomycin D. These observations, together with other findings, suggested that the mRNA was being converted into some nonextractable and nontranslated form, probably by binding of a glucocorticoid-induced protein to the conserved 3' untranslated region. In order to investigate further the nature of this phenomenon, seven different literature procedures were evaluated for extracting and determining the PG synthase mRNA. Five of the seven procedures failed to detect hybridizable PG synthase mRNA in glucocorticoid-treated cells. Two procedures, however, recovered mRNA in both glucocorticoid-treated and control cells. A comparison of the protocols indicated that only those methods that incorporate a cationic detergent (sodium N lauroylsarcosine), instead of anionic detergents in the lysis or homogenization buffers, successfully extract the glucocorticoid-suppressed PG synthase mRNA. Based upon these results two procedures are described, one that optimizes the extraction and determination of the glucocorticoid-suppressed (cryptic) form of the mRNA, and another which optimizes the analysis of normal mRNA without extracting the cryptic form. The results indicate that translational control of PG synthase by glucocorticoids is regulated by converting the mRNA into a cryptic form that is more firmly tissue bound than normal mRNA. PMID- 1909511 TI - Do acuity systems work? PMID- 1909510 TI - Histopathological study of von Ebner's lingual salivary glands in Trypanosoma cruzi-infected mice. AB - In the present study we describe the histopathological alterations induced by RC strain of Trypanosoma cruzi in the mouse von Ebner's lingual salivary glands during the acute period of infection: Amastigotes were found in von Ebner's gland acini cells, excretory duct cells, intralobular connective tissue, inside the acini lumen and muscle fibres. Desorganized parenchyma with impairment at the acinar and duct level, and intense lymphoplasmocytic infiltrate were seen. PMID- 1909512 TI - Preneoplastic transformation in mouse mammary tissue: identification and validation of intermediate biomarkers for chemoprevention. AB - Specific and sensitive markers capable of determining the extent of tumorigenesis are important end points not only for evaluating the carcinogenic potency, but also for assessment of chemopreventive efficacy of modulators. Prototypic mammary carcinogens induce a high frequency of mammary adenocarcinomas. The appearance of tumors, however, is a culmination of initiational and promotional events whose modulation may constitute an effective means for chemopreventive interventions. The purpose of this study was i) to identify intermediate biomarkers for mammary cell transformation and ii) to apply these biomarkers and validate the ability of selected fatty acids to modulate chemical carcinogen-induced tumorigenic transformation. An in vitro model derived from mouse mammary explant cultures was utilized to examine the effects of 7,12 dimethylbenz (a) anthracene (DMBA), a prototype chemical carcinogen for rodent mammary gland. The effects of DMBA exposure were quantified at the molecular level by determining induction of oncogene expression, at metabolic level by determining the extent of estradiol metabolism, and at cellular level by determining the emergence of hormone independent mammary alveolar lesions (MAL) and their tumorigenic potential. DMBA treatment induced binding of ras oncogene product ras p21 to [alpha 32P] GTP, altered estradiol metabolism by increasing the ratio of C16 alpha/C2 hydroxylation in favor of 16 alpha-OHE1 formation, and exhibited high frequency of MAL. Transplantation of cells from these MAL produced rapidly growing tumors. Treatment of DMBA-exposed cultures with polyunsaturated n-6 fatty acids enhanced, and treatment with polyunsaturated n-3 fatty acid suppressed the molecular, metabolic and cellular intermediate biomarkers for tumorigenic transformation. Thus, oncogene expression, estradiol metabolism and formation of MAL may constitute useful molecular, metabolic and cellular intermediate biomarkers. Alteration of these biomarkers by selected fatty acids is suggestive of their utility as end points for the chemopreventive efficacy of dietary agents. PMID- 1909513 TI - Inhibition by lombricine from earthworm (Lumbricus terrestris) of the growth of spontaneous mammary tumours in SHN mice. AB - The effects of lombricine extracted and purified from earthworm (Lumbricus terrestris) skin on the growth of palpable sizes (approximately 5 mm) of spontaneous mammary tumours were studied in SHN mice. In Experiment 1, daily subcutaneous injections of lombricine (0.3 mg/0.05 ml olive oil) inhibited markedly the growth of tumours associated with the retardation of the growth of preneoplastic mammary hyperplastic alveolar nodules. In 1H-NMR spectra, the experimental mice had lower serum levels of lactic acid and glucose than the control. On the other hand, urine of the former group contained higher levels of allantoin, creatine and creatinine than that of the latter. In Experiment 2, lombricine given as diet at the concentration of 120 mg/kg also inhibited the growth of tumours, though to a lesser degree than the injection. The treatment had little effect on 1H-NMR spectra of either serum or urine and normal and preneoplastic mammary gland growth. All results indicate that the inhibition by lombricine of the growth of mammary tumours is at least partly due to the maintenance of homeostasis of the body including the regulation of the excess uptake of glucose as a source of energy and nutrition. PMID- 1909514 TI - Evaluation of cytokine levels in whole cell cultures of patients with gynaecological tumors as diagnostic parameters. AB - The measurement of the cytokine production of activated lymphocytes and monocytes supposedly provides a tool for evaluating the actual status of the cellular immunity potential of a person. We measured the levels of IFN-gamma and IL-1 alpha in the 4 day post-induction supernatants of mitogen-stimulated unseparated blood cell cultures by a rapid and sensitive immunoassay using various monoclonal and polyclonal antibodies. With this reproducible and easy-to-handle system we tested 90 patients with primary gynaecological tumors and the same number of age matched female controls. In the blood cell cultures of the tumor patients significantly lower values of IFN-gamma and IL-1-alpha were observed, although lymphocyte and monocyte counts were almost normal. There was also a difference in the IFN-gamma-levels between the four tumors, in as much as patients with ovarian and endometrial carcinomas had significantly lower values than patients with breast and cervical carcinomas. PMID- 1909515 TI - Cross-resistance of human multidrug-resistant cells to mitomycin C. AB - Human multidrug-resistant cells, K562/ADM, KB-C-4, AdrRMCF-7 and CEM/VLB100 showed 21-, 7.5-, 105- and 3.4-fold cross-resistance to mitomycin C (MMC). The resistance to MMC in K562/ADM, KB-C-4, AdrRMCF-7, CEM/VLB100 cells was reversed by 6.6 microM verapamil. Accumulation of [3H]MMC in K562/ADM, AdrRMCF-7 and CEM/VLB100 cells also decreased by 37, 26 and 33%, as compared with their drug sensitive counterparts. In KB-C-4 cells, accumulation of [3H]MMC decreased by 60%, and efflux rate of [3H]MMC was slightly increased as compared to their parental KB-3-1 cells. Verapamil at 6.6 microM increased accumulation of [3H]MMC in these multidrug-resistant sublines. K562/ADM10, K562/ADM50, K562/ADM100 and K562/ADM250 cells, which showed 17- to 230-fold resistance to Adriamycin, also showed 0.8- to 7.3-fold cross-resistance to MMC. In these cell lines, the extent of resistance to Adriamycin (ADM) that was consistent with expression levels of P glycoprotein shown by immunoblotting was directly proportional to the extent of their resistance to MMC. Regression analysis indicated that relative resistance to Adriamycin was correlated with relative resistance to MMC (r = 0.98). These results indicate that MMC can be transported by P-glycoprotein overexpressed in multidrug-resistant cells. PMID- 1909516 TI - [State of the art in radiotherapy of laryngeal and nasopharyngeal carcinoma]. AB - Rapid evolution in radiological diagnostic and therapeutic technology has developed the precision radiation therapy in the past two decades. The new technology has improved the loco-regional control of tumor, survival as a result of better loco-regional control, and the quality of life of head and neck cancer patients by reducing treatment-related complications. Five-year recurrence free survival of T1N0 glottic carcinoma has increased to 95% from 77% over the past 30 years by means of improved therapeutic equipment and use of additional treatment devices, such as immobilization shell and wedge filter. On the other hand, arytenoid edema which resulted in husky voice after radiation therapy was more infrequently observed in patient treated with lesser treatment volume. Overall 5 year survival of nasopharyngeal cancer patients has been also improved to 52% from 42% during the past 20 years. Replacement of telecobalt unit by linear accelerator and practical use of computed tomography have impacted on the above improved survival. More recently, intracavitary technique and immunological diagnostic procedure have been investigated to improve better local control and survival of nasopharyngeal cancer patient. PMID- 1909517 TI - Haemostatic factors associated with vascular thrombosis in patients with systemic lupus erythematosus and the lupus anticoagulant. AB - To elucidate the mechanism of vascular thrombosis in patients with systemic lupus erythematosus and the lupus anticoagulant changes in factors associated with haemostasis were investigated. The lupus anticoagulant was associated with an increased incidence of thrombosis, particularly cerebral thrombosis. Concentrations of fibrinopeptide A and fibrinopeptide B beta 15-42 were significantly raised in the plasma of patients with systemic lupus erythematosus and the anticoagulant compared with concentrations in patients without the lupus anticoagulant. The tendency towards formation of thrombosis was not found in all lupus patients with the anticoagulant, however. Concentrations of thromboxane B2 were remarkably raised in the plasma of the two patients with the lupus anticoagulant who had recently had thrombosis. Concentrations of 6-keto prostaglandin F1 alpha, protein C, antithrombin III, and plasminogen were similar in both groups. No significant decrease in serum stimulatory activity on prostacyclin production by cultured aortic endothelial cells was noted in lupus patients with the anticoagulant, but inhibition was present in the two patients with recent thrombosis. These results indicate that although patients with the lupus anticoagulant are not always in a hypercoagulable state, haemostatic abnormalities found in some patients with the anticoagulant may be predictive of thrombotic events. PMID- 1909518 TI - Lupus anticoagulant: clinical significance in anticardiolipin positive patients with systemic lupus erythematosus. AB - The significance of anticardiolipin antibodies and the lupus anticoagulant was studied in 58 consecutive patients with systemic lupus erythematosus. On 85 occasions serum IgG and IgM anticardiolipin antibodies were measured by an enzyme linked immunosorbent assay (ELISA), and simultaneous plasma samples tested for lupus anticoagulant activity. The most significant association with clinical events (previous thrombosis or thrombocytopenia occurring in 11/58 patients) was with prolonged tissue thromboplastin inhibition time (TTIT) followed by prolonged kaolin cephalin clotting time (KCCT) then raised IgG anticardiolipin antibody concentrations and dilute Russell's viper venom time. Although IgG anticardiolipin antibodies or KCCT were the most sensitive tests in identifying this group, the TTIT was the most specific (98%). Nine patients were IgG anticardiolipin antibody positive and lupus anticoagulant negative, of whom one had thrombocytopenia but none had thrombosis. The presence of a lupus anticoagulant in anticardiolipin antibody positive patients increases specificity for certain adverse clinical events. PMID- 1909519 TI - An unusual presentation of gonococcal arthritis in an HIV positive patient. AB - A 27 year old, HIV positive, homosexual man was admitted for evaluation and treatment of acute oligoarticular arthritis. Gonococcal arthritis was found in a single hip and a single sternoclavicular joint, which is an unusual distribution for this bacterial pathogen. PMID- 1909521 TI - Recurrent hypoglycemia secondary to drug-dispensing error. AB - We present three patients who developed hypoglycemia due to inadvertent dispensing of sulfonylurea drugs. Each patient had a similar clinical course characterized by hypoglycemia that remitted during hospitalization and recurred after discharge. The cause of the hypoglycemia was determined only after close inspection of the patients' medications, not the label on the container. Our experience suggests that hypoglycemia due to drug-dispensing error may be more common than is generally recognized. PMID- 1909520 TI - Positive chronotropic and inotropic responses to release of norepinephrine from sympathetic nerve terminals produced by nitroglycerin in atria. AB - Nitroglycerin produced concentration-dependent increases in spontaneous rate and enhancements of positive chronotropic and inotropic responses to transmural stimulation of isolated right guinea-pig atria. The effects of nitroglycerin were significantly potentiated by desmethylimipramine, which is an inhibitor of norepinephrine uptake, and were significantly inhibited by either guanethidine, which inhibits release of norepinephrine, or alpha-methyl-p-tyrosine, which inhibits synthesis of norepinephrine. The effects of nitroglycerin were not modified by either prazosin or atropine, but were significantly inhibited by either the beta-adrenoceptor antagonist propranolol or the alpha 2-adrenoceptor antagonist yohimbine. Nitroglycerin significantly increased the concentration of norepinephrine in the medium bathing atria and the 3,4-dihydroxyphenylglycol concentration in the atrial tissue, which were quantified using high-performance liquid chromatography with electrochemical detection. The atrial responses to nitroglycerin appear to mimic sympathetic neuronal activities and may involve the modulatory role of alpha 2-adrenoceptors in the release of norepinephrine. PMID- 1909522 TI - [Drowning in the bath tub after choking: Unusual death, accident or suicide? Reconstruction of an unusual fall]. AB - A thirteen-year old girl attending a special school who had been suffering from genuine epilepsy for about one year was found dead completely clothed in the full bathtub in the bathroom of her parent's flat. The characteristic features of death by drowning but also signs of strangulation as well as a condition after shackling of the hands were found in the forensic post-mortem examination and autopsy. The putative strangulation instrument was a pair of tights which was floating in the bathwater. The hands were probably tied with the lace of a sneaker. In the further course of events, the inquiries and investigations initially commenced on the assumption of a capital crime gave reason to consider suicide. A reconstruction experiment under comparable external conditions indicates that this is possible. From a forensic-psychiatric point of view, an exacerbative mental crisis situation can be inferred as a final motive from the known personality configuration and the immediate circumstances. The tragic outcome in the final phase appears to have been determined by the additional complication of a provoked grand mal epilepsy attack. All in all, this hypothesis is the most plausible. However, subjective and objective observations do not rule out the possibility of homicide. PMID- 1909523 TI - Total protozoa counts and ammonia in the rumen of mature dry Friesian cows on hay based rations. AB - The present work was an attempt to determine whether the variations in ruminal ammonia concentrations could be directly correlated to corresponding changes in total protozoa numbers of cattle. Four dry Friesian cows fed with hay-based rations were used through several experiments in which the twice daily feeding (6.15-15.30 h) as well as a 30 h-fasting period were studied. Simultaneously to a continuous or a regular collection of rumen liquor (for NH3), samples of rumen contents (for total protozoa numbers) were regularly withdrawn from the ventral sac. Any definite nycthemeral cycle of the protozoa numbers could not be related to feeding time. Moreover, no significant relationship could be found between the ruminal ammonia and the corresponding total protozoa numbers measured in the nocturnal interprandial period or during starvation. The data suggest that the nycthemeral ammonia profiles recorded in cattle are not directly related to protozoal activity. PMID- 1909524 TI - Electrocardiographic changes in chronic Trypanosoma cruzi infected Cebus apella monkeys. AB - PURPOSE: To evaluate electrocardiographic data of Cebus apella monkeys with Chagas' disease. MATERIAL AND METHODS: 53 Cebus apella monkeys (juvenile and adult of both sexes) were used: 35 as a control group and 18 inoculated four-five years ago with 3 different Trypanosoma cruzi strains (CA1, n = 10; Colombian, n = 4; Tulahuen, n = 4). RESULTS: The normal electrocardiogram (ECG) showed differences with that of man, a) high cardiac rate; b) presence of "pulmonary p" wave without pulmonary pathology. The ECT alterations found between 11 and 58 months after last inoculation were: right bundle branch block; intermittent right bundle branch block; left ventricle overload; repolarization disturbances; left anterior hemiblock; extra systole. These alterations resemble those found in humans, as well as clinical parasitological and immunological alterations. Their incidence and the time at which they appeared, seem to vary according to the route, strain, inoculum and frequency of the inoculation. Three of the monkeys died spontaneously 46, 48 and 52 months after the infections due to the natural evolution of the disease, and six were sacrificed during the follow-up. In both cases histopathological lesions were found, and their intensity was directly related to the time and resembled the human disease. CONCLUSION: The Cebus apella, as it reproduces human electrocardiographic and histopathological alterations, a short time after experimental infection, is a suitable model for the study of the different aspects of the physiopathology, immunopathology and therapeutics of the indeterminate and chronic phases of Chagas' disease. PMID- 1909525 TI - The role of safety cues in mediating the response to inhalations of CO2 in agoraphobics. AB - Eighteen subjects meeting DSM-III-R criteria for panic disorder with agoraphobia were randomly allocated to either a safety or non-safety condition and underwent 15 min inhalations of 5.5% CO2 in air. In the safety condition, both a senior and junior experimenter were present, the junior experimenter was presented as a professional, and subjects were in personal contact with the senior experimenter throughout the procedure. In the non-safety condition, the senior experimenter left on a bogus emergency, the junior experimenter was introduced as a "student" and was dressed casually, and subjects were alone in the experimental room throughout the procedure. Despite these dramatic manipulations, there was no significant difference between groups on either the number of subjects experiencing a panic attack or on pre-inhalation safety scores. However, a median split analysis on safety scores indicated that those subjects who perceived themselves to be less safe before the inhalation were more likely to experience a panic attack. PMID- 1909526 TI - Protection of rats against the effects of alpha-naphthylthiourea (ANTU) by elevation of non-protein sulphydryl levels. AB - We have investigated the influence of the elevation of pulmonary glutathione (GSH) levels on the toxicity of the rodenticide alpha-naphthylthiourea (ANTU) to rat lung. Administration of phorone (diisopropylidene acetone; 200 mg/kg i.p.) caused an initial depletion of both pulmonary and hepatic GSH followed after 48 hr by a marked elevation in both tissues, due most probably to a compensatory rebound synthesis. In control rats, ANTU produced a dose-dependent lethality, hydrothorax and loss of ability of lung tissue to accumulate adenosine and spermidine (markers of endothelial and epithelial cell function, respectively). These effects were prevented or markedly ameliorated when ANTU was given 48 hr after pretreatment with phorone. The mechanism of the protection by phorone pretreatment against ANTU-induced pulmonary toxicity is unclear. It may be due, in part, to elevated GSH levels in pulmonary endothelial cells and, in addition, to increased detoxification of ANTU in the liver, resulting in a decreased availability to the lung. PMID- 1909527 TI - Pertussis and cholera toxins inhibit prostaglandin synthesis in rat astrocyte cultures at distinct metabolic steps. AB - The influence of pertussis and cholera toxin-sensitive G-proteins in the prostaglandin synthetic pathway has been investigated. Prostaglandin D2 (PGD2) synthesis was stimulated by the calcium ionophore A23187, the phorbol ester tetradecanoylphorbol acetate (TPA), or by extracellular ATP. Pretreatment of cultures with pertussis toxin (Ptx) resulted in a partial inhibition of PGD2 synthesis in both stimulated and unstimulated cells. A23187-stimulated PGD2 synthesis was affected less than ATP- or TPA-stimulated synthesis. Furthermore, Ptx also inhibited A23187-, ATP-, and TPA-stimulated arachidonic acid release. Basal and stimulated PGD2 synthesis were also inhibited, when cultures were preincubated with cholera toxin (Ctx). Here, ATP-stimulated synthesis was affected the most. Arachidonic acid release, in contrast, was enhanced by cholera toxin, even without addition of stimuli. These data suggest that regulation of prostaglandin synthesis in rat astrocyte cultures involves Ptx- and Ctx-sensitive G-proteins. Ptx substrates affect events at or proximal to phospholipase A2, whereas Ctx substrates influence events proximal or distal to phospholipase A2. PMID- 1909528 TI - Spirohydantoin inhibitors of aldose reductase inhibit iron- and copper-catalysed ascorbate oxidation in vitro. AB - Transition metal-catalysed oxidations have been implicated in the complications of diabetes. We report here that some experimental inhibitors of the enzyme aldose reductase (implicated in diabetes mellitus via its ability to catalyse glucose reduction to sorbitol) are also potent inhibitors of transition metal catalysed ascorbate oxidation. The inhibition appears to be dependent upon the presence of a spirohydantoin group. It is conceivable that the copper- and iron binding capacity of these compounds may contribute to some of their observed biological effects and may provide a starting point for a new generation of experimental drugs for the treatment of diabetes mellitus. PMID- 1909529 TI - Effect of zidovudine (AZT) on reproductive and hematopoietic systems in the male rat. AB - The effects of Zidovudine (AZT) on parameters of the reproductive and hematopoietic systems of male rats were evaluated and compared to those of the controls. Young male Wistar rats were divided into three groups. The control rats (Group 1) received no drug. AZT was administered via drinking water to rats in Groups 2 and 3 (0.1 mg/mL Group 2, and 1.0 mg/mL Group 3) for 4 weeks. Daily water intake and weekly body weight were monitored. Serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T), prolactin (PRL) and intratesticular T levels were determined by specific radioimmunoassays. Serum AZT was measured by HPLC. Bone-marrow toxicity was monitored by colony-forming units of erythroid (CFU-E) and granulocyte-macrophage (CFU-GM) assays. The body weight of all rats increased 2-fold in four weeks, and no significant differences were observed between control and treated groups. Ventral prostate (VP) weight decreased significantly (P less than 0.05) by 32% in Group 2 and 27% in Group 3 rats, compared to the control group. Seminal vesicle (SV) weight decreased by 20% in Group 2 (NS) and 30% in Group 3 (P less than 0.05) rats. No significant differences were observed in testes weight or in the intratesticular sperm count between control and AZT-treated groups. Serum T levels (ng/mL) decreased significantly in Group 2 rats (2.8 +/- 0.4 in control to 1.7 +/- 0.2, P less than 0.05) but recovered (2.6 +/- 0.5) in Group 3 when compared to Group 1 (control). Serum LH and PRL levels showed a significant increase (P less than 0.05) in Group 3 compared to control or Group 2 rats. Serum FSH and intratesticular T levels showed no significant change. A significant (P less than 0.05) dose-dependent decrease in CFU-E and in CFU-GM was observed in AZT-treated rats compared to controls. These results demonstrate that the effects of AZT on the reproductive system in the male rat are more subtle and complex, compared to its significant effects on bone-marrow. This suggests that important interactions may exist between the endocrine and hematopoietic systems. PMID- 1909530 TI - Is amyloidogenesis during Alzheimer's disease due to an IL-1-/IL-6-mediated 'acute phase response' in the brain? AB - Alzheimer's disease is characterized by the presence of amyloid plaques in the brain, which comprise mainly beta-amyloid peptide and alpha 1-antichymotrypsin. Here, Peter Vandenabeele and Walter Fiers advance the hypothesis that this amyloidogenesis results from an IL-1-/IL-6-mediated acute phase reaction in the brain. They propose possible intracerebral sources of cytokines and acute phase proteins in microglia, astrocytes, neurons and cells of the choroid plexus. PMID- 1909531 TI - Serological status for HBV and HCV infection in anti-HIV seropositive and seronegative intravenous drug abusers. PMID- 1909532 TI - Kallmann's syndrome and chemosensory evoked potentials. AB - Kallmann's syndrome is generally assessed by history and subjective tests of olfactory function. In this study three patients suffering from Kallmann's syndrome were investigated with more objective techniques, including the recording of chemosensory evoked potentials (CSEPs). After testing olfactory function by means of a simple odor identification test, anosmia was confirmed in only one patient, since the other two patients were able to distinguish between several odorants. However, investigations in which CSEPs were employed indicated that all three patients had complete loss of their olfaction as well as hypersensitivity of the trigeminal nerve. These findings prove the usefulness of CSEPs in clinical investigations of the sense of smell. PMID- 1909533 TI - [Molecular cloning of alpha-amylase gene from Bacillus megaterium and its expression in Bacillus subtilis]. AB - Using Bacteriophage lambda and plasmid pAT153 and pNQ122 as vectors, alpha Amylase gene from B. megaterium has been cloned into both hosts of E. coli and B. subtilis. Expression level of the gene is 250 times higher than B. megaterium when it resides in B. subtilis. The enzyme produced by B. subtilis harboring the hybrid plasmid can digest amylase into maltose and maltotriose at first, then turn them to maltose and glucose, as incubation time extended. It also can digest maltotriose to maltose and glucose. As a control, the extracts from the broth of recipient strain have no detectable amylase activities. Therefore the enzyme coded by this gene is defined as saccharifying type alpha-amylase. Its molecular weight is about 58,000 daltons. PMID- 1909534 TI - Failure of intravenous infusions in neonates. AB - The median life expectancy (survival) of 286 peripheral intravenous infusion sites in 105 babies in a children's intensive care unit was 36 h. Unadjusted univariate survival analysis revealed that dextrose infusions and the initial infusions received by a baby had longer survival than total parenteral nutrition (TPN) infusions and later infusions respectively. Also infusions with cloxacillin and penicillin survived for longer than average while infusions with phenytoin had reduced survival. Gestational age, weight, infusion site, other drugs, co infusion of Intralipid with TPN solutions and neutralization of TPN did not influence survival of infusions. Multivariate survival analysis confirmed the findings for TPN and penicillin but not for cloxacillin, phenytoin or later infusions. Multivariate analysis also suggested that survival was improved with ampicillin and aminophylline and worse for leg sites, for older babies and for infusions in which the fluids were given at greater rates. It also indicated that neutralization of TPN improved survival. PMID- 1909535 TI - Delivery of vitamin A from parenteral nutrition solutions in neonates. AB - The delivery of Vitamin A from parenteral nutrition may be suboptimal. To investigate this sample solutions were prepared and Vitamins A and E concentrations from the solution bags and the efflux from the lines were measured over a 24 h period. The results show that mean Vitamin A levels in the solution bags declined from a range of 57-66% to 17% of expected over 24 h and at the efflux of the lines from a range of 13-29% to 4% of expected, giving a calculated delivery of 10% of expected. There is no improvement with light protection or an ethylene vinyl acetate system. Mixing the vitamin preparation in lipid showed less decline (from 92 to 70% of expected over 24 h), but the delivery was variable. When vitamins were added to a lipid-dextrose-amino acid solution, there was minimal loss from the solution bag and line with a calculated delivery of 94% of expected. The delivery of Vitamin E from all systems was constant with a mean calculated delivery of 74% of expected. It was concluded that the mixing of multivitamins in dextrose-amino acid-electrolyte solutions results in poor delivery of Vitamin A and this is improved by mixing lipid solution. This is important in preterm infants who are prone to become Vitamin A deficient. PMID- 1909536 TI - The natural history of untreated phenylketonuria over 20 years. AB - Fifty-one adults with untreated phenylketonuria (PKU), have been reviewed after a 20 year interval, at ages ranging from 28.8 to 71.8 years. Five died of causes unrelated to PKU. Three severely affected individuals had shown a progressive loss of motor function and three had developed epilepsy, bringing the total with this problem to 12. No loss of abilities was apparent in 41 patients. Other health problems, including cataracts, were not frequent. Serum phenylalanine levels had decreased over the 20 year period. Untreated PKU does not generally cause progressive loss of abilities during adult life. PMID- 1909537 TI - [The effect of chronic treatment of deprenyl in animal models of Parkinson's disease]. AB - Recent studies have demonstrated that deprenyl can delay the progression of parkinsonian syndrome. Deprenyl selectively and irreversibly inhibits the activity of monoamine oxidase-type B (MAO-B), and subsequent enzyme activity requires de novo synthesis of MAO-B. In this study we investigated (1); the effects of deprenyl on striatal dopamine (DA) levels in MPTP-lesioned and undamaged mice and (2); the effect of deprenyl on L-DOPA induced rotational movements in a hemiparkinsonian model monkey. In MPTP-lesioned mice, deprenyl increased the striatal DA levels by 123%, 78% immediately and one week after termination of deprenyl treatment respectively, while by 31%, 24% in MPTP undamaged mice, respectively. Four weeks after termination of treatment, and the striatal DA was not significant. It shows that deprenyl is effective in elevation of striatal DA at least one week after termination of treatment, and the degree of increase of striatal DA following deprenyl treatment is greater in MPTP treated mice than in undamaged mice. Deprenyl seemed to be effective longer in a hemiparkinsonian monkey than in rodents. The result suggests that less frequent administration of deprenyl may be effective in controlling side effects of L-DOPA without reducing therapeutic efficacy. PMID- 1909538 TI - Unlimited claims on limited resources: entropy, health care, and a hospice world view. Third in a series. PMID- 1909539 TI - Roles of the liver and kidney in acid-base regulation and its disorders. PMID- 1909540 TI - Transdermal nitrate therapy: bioavailability during exercise increases transiently after the daily change of patch. AB - Ten volunteers carried a 10 mg 24 h -1 transdermal glyceryl trinitrate (GTN) patch for 24 h before moderate exercise. Plasma GTN-concentration increased significantly (P less than 0.05) by 19% to peak value at 15 min. Two hours after patch renewal repeat exercise increased GTN concentration by 56% (P less than 0.001). The two nitrate-concentration curves differed significantly (P less than 0.0001). Thus, change of patch augmented nitrate availability during exercise. PMID- 1909541 TI - Reduction of LDL cholesterol by pravastatin does not influence platelet activation in patients with mild hypercholesterolaemia at risk of coronary heart disease. AB - The effect of pravastatin on low density lipoprotein (LDL) cholesterol and platelet activation was studied in 16 patients with mild hypercholesterolaemia who had two or more additional cardiovascular risk factors. Patients were treated with either pravastatin (20-40 mg day-1) or placebo for 1 year. Plasma LDL and urinary excretion of 2,3-dinor-thromboxane B2 (an index of platelet activation in vivo) were determined at 0, 3, 6 and 12 months. There was a significant reduction in LDL at 6 and 12 months (2P less than 0.05) but this was not associated with any significant change in thromboxane metabolite excretion. PMID- 1909543 TI - Implementation of breast cancer screening. AB - Mammography, breast physical examination, and breast self-examination are recommended for breast cancer screening. Although in randomized trials of screening, mammography demonstrated a reduction in breast cancer mortality for women over 50, such data are not available for breast physical or self examination. The Canadian National Breast Screening Study should provide data regarding the efficacy of breast physical examination alone. The World Health Organization has established trials to evaluate self-examination in the USSR and Germany. There is still controversy regarding routine mammographic screening and the optimal screening interval for women under age 50. The costs of mammographic screening remain a concern, but these costs can be lessened considerably through efficiency of mammographic services and a reduction in the number of false positive interpretations that prompt biopsy. Primary care physicians can help to reduce breast cancer mortality by referring their patients for screening mammography and by performing breast physical examinations. PMID- 1909542 TI - The effect of various drugs on the glucuronidation of zidovudine (azidothymidine; AZT) by human liver microsomes. AB - 1. Zidovudine (3'-azido-3'-deoxythymidine; AZT) is the drug of proven efficacy available for the treatment of patients with AIDS or ARC. It is eliminated mainly by hepatic glucuronidation. Therefore, interference with this metabolic pathway may lead to enhancement of AZT effect or to increased toxicity of the drug. We have examined the effect of a number of drugs which themselves undergo glucuronidation on AZT conjugation by human liver microsomes in vitro. 2. AZT glucuronidation followed Michaelis-Menten kinetics. The apparent Km and Vmax values (mean +/- s.d., n = 5), were 2.60 +/- 0.52 mM and 68.0 +/- 23.4 nmol h-1 mg-1, respectively, as determined from Eadie-Hofstee plots. 3. Dideoxyinosine, sulphanilamide and paracetamol were essentially non-inhibitory at concentrations up to 10 mM (4 times the concentration of AZT in the incubation). The most marked inhibitory effects were seen with indomethacin, naproxen, chloramphenicol, probenecid and ethinyloestradiol, with enzyme activity decreased by 97.7, 94.9, 88.7, 83.4% and 79.0%, respectively, at a concentration of 10 mM. Other compounds producing some inhibition of AZT conjugation were oxazepam, salicylic acid and acetylsalicylic acid. 4. Further studies are necessary to characterise the inhibition observed but the method described enables a screen of potentially important drug interactions to be carried out. PMID- 1909544 TI - A comparative study of the 'FDA' and 'USDA' methods for the detection of Listeria monocytogenes in foods. AB - Nineteen laboratories across Canada took part in a comparative study of the 'FDA' and 'USDA' methods for the detection of Listeria monocytogenes in foods and environmental samples. The results show that the enrichment period of the FDA method can be shortened from 7 to 2 days without substantially reducing the number of positive samples. With a limited number of samples, the USDA method proved to be slightly more efficient in isolating L. monocytogenes than the FDA method. Fraser broth, in principle, proved to be useful as a screening tool but is not very selective. Oxford agar and lithium chloride-phenylethanol-moxalactam medium were better than modified McBride's agar in isolating this microorganism. PMID- 1909545 TI - Antagonistic effect of coryneform bacteria from red smear cheese against Listeria species. AB - A total of 187 coryneform bacteria were isolated from red smear and screened for inhibitory effects against 16 strains of Listeria species. Culture filtrates from Brevibacterium linens (16 strains), Arthrobacter nicotianae (4 strains) and Arthrobacter nucleogenes (3 strains) showed clear zones of inhibition. The antagonistic effect was seen against 26 to 87% of 91 Listeria strains tested. A. nicotianae and A. nucleogenes were more effective against Listeria innocua and Listeria ivanovii than against Listeria monocytogenes. No species specifically was observed for B. linens, but there was a difference regarding the inhibitory activity of individual culture filtrates. When culture filtrates of the test strains were added to Listeria broth cultures, the maximum growth level was not attained. Inhibition in broth cultures was dependent on the concentration of culture filtrates. Culture filtrates from the late stationary phase had a stronger inhibitory effect on the growth of L. monocytogenes. The nature of the inhibitory effects remained unclear. Attempts to characterize the nature of the antagonism showed that the culture filtrates lost their inhibitory activity upon heating, and the molecular size of the inhibitory substances were greater than 12 14 kDa. PMID- 1909546 TI - The occurrence and growth of microorganisms during the fermentation of fish sausage. AB - Minced fish (mullet) sausage mixes containing added sugar, salt, nitrate, nitrite and spices were fermented (48 h, 30 degrees C) by indigenous flora or by a starter culture (Pediococcus acidilactici) and the microbial ecology and behaviour of various bacteria was monitored. Pediococcus pentosaceus and Lactobacillus plantarum dominated the indigenous fermentation, achieving populations of 10(7)-10(8) cfu/g by 48 h, and decreasing the pH of the mix to 4.5 4.7. Significant growth (10(5)-10(7) cfu/g) of Staphylococcus warneri, Staphylococcus aureus, Staphylococcus epidermidis. Micrococcus varians and Micrococcus luteus also occurred during this fermentation. Less growth was exhibited by Bacillus megaterium and yeasts. Pediococcus acidilactici dominated the fermentation when it was inoculated as a starter culture, but indigenous lactic acid bacteria (P. pentosaceus and L. plantarum) also grew to 10(7)-10(8) cfu/g. The growth of other bacteria and yeasts was restricted during fermentation with starter culture. Inoculated Escherichia coli, Salmonella typhimurium, Salmonella sofia, and Staphylococcus aureus grew to 10(6)-10(7) cfu/g in the sausage mix during indigenous fermentation. Lesser growth occurred for Bacillus cereus, Clostridium perfringens and Vibrio parahaemolyticus. Growth of these bacteria was significantly inhibited in sausage mix fermented with P. acidilactici. PMID- 1909547 TI - Incidence of heat-resistant fungi in Nsukka, southern Nigeria. AB - A total of 42 soil samples collected from different parts of Nsukka, Southern Nigeria, and 20 freshly plucked mango fruits were screened for the presence of heat-resistant fungi. Each soil sample, suspended in sterile water, and washings from each mango fruit were separately heated at 70 degrees C for 1 h before plating on double-strength potato dextrose agar containing chloramphenicol and incubating at approx. 28 degrees C. Approximately 98% of all soil samples and 17% of mango fruits contained heat-resistant fungi which were identified as Neosartorya fischeri, N. fischeri var. spinosa, Aspergillus flavus, Penicillium citrinum and Paecilomyces varioti which has not been reported in tropical soil. Neosartorya spp. were predominant and occurred in all positive samples. Fungal counts ranged from non-detectable to 200 colony-forming units per 10 g of soil. Most isolates appeared to grow faster at 35 degrees C than at 30 degrees C and 40 degrees C. PMID- 1909548 TI - Listeria monocytogenes in foods in Norway. AB - Three-hundred-and-eighty-two samples of different retail food items in Norway (imported soft cheese, raw chicken, minced meat, fermented sausages, vacuum packed processed meat products, smoked salmon, peeled shrimps, raw minced fish) and 78 carcass samples (sheep, pig, cattle), were screened for Listeria monocytogenes. Of the 460 samples investigated, 78 were found to contain L. monocytogenes. Five of these contained greater than 10(3) cfu/g, four greater than 10(2) cfu/g, while the remainder were shown to contain L. monocytogenes only after enrichment. L. monocytogenes was isolated most frequently from raw chicken, sporadically from soft cheese, shrimps, processed meat products and smoked salmon, and not at all from carcasses and fermented sausages. PMID- 1909549 TI - Romania. Crisis in caring. PMID- 1909550 TI - Continuing education: brushstrokes in learning. PMID- 1909551 TI - Nurse recruitment from overseas. PMID- 1909552 TI - Caesarean section: maternal risks. PMID- 1909553 TI - Understanding speech disorders. PMID- 1909554 TI - Health care research methods. Part 1. PMID- 1909555 TI - Working parents: practice makes imperfect. PMID- 1909556 TI - Support groups. Caring about each other. PMID- 1909557 TI - Support groups. Setting up groups: a practical guide. PMID- 1909558 TI - Support groups: a personal view. PMID- 1909559 TI - Pharmacokinetics of encainide in patients with cirrhosis. AB - The pharmacokinetics of encainide were investigated in 10 patients with cirrhosis and 10 matched controls following single intravenous (IV, 25 mg), single oral (so, 25 mg), and multiple oral (mo, 25 mg thrice daily over 5 days) dosing. The hepatic oxidative drug-metabolizing enzyme capacity and its inducibility were assessed by antipyrine elimination and 6-beta-hydroxycortisol excretion. Eight controls and nine patients were of the extensive metabolizer phenotype (EM), as assessed by the sparteine metabolic ratio. Statistics was performed in EM only. The antipyrine half-life was significantly longer and clearance was significantly lower in patients with cirrhosis. Following IV administration, no significant differences in encainide half-life clearance, volume of distribution, or the area under the plasma concentration time curve (AUC) were observed between patients and controls. Following so and mo, there was a fourfold reduction in the oral clearance in cirrhotics. Thus, encainide bioavailability was increased in cirrhosis. Whereas the AUC of encainide was significantly higher in patients, no differences were observed in its active metabolites, O-desmethyl-encainide (ODE) and 3-methoxy-O-desmethylencainide (MODE). Plasma concentrations of encainide and its metabolites after 3 and 5 days of mo suggested steady-state conditions after 3 days of oral dosing. No change in antipyrine elimination and 6-beta hydroxycortisol excretion following mo occurred. There was no relationship between parameters of encainide and antipyrine elimination. In conclusion, even though the elimination of encainide was reduced in patients with cirrhosis, plasma levels of the pharmacologically active metabolites, ODE and MODE, were comparable.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1909560 TI - Effect of encainide, ODE, MODE, and flecainide on ADP/5-HT induced platelet aggregation and in the anesthetized dog coronary artery stenosis-occlusion model of intravascular thrombosis. AB - Encainide is a class 1C antiarrhythmic agent that is indicated for the treatment of life-threatening arrhythmias, such as sustained ventricular tachycardia. Furthermore, encainide possesses a moderate degree of antiserotonin activity, which was quantitated in this present study by determining displacement of [3H]spiperone binding from rat cortical 5-HT2 binding sites. The Ki for encainide in this model was 66.1 nM, compared to 2.6 nM for ketanserin. Two encainide metabolites, ODE and MODE, were also active, but were weaker than encainide. Additionally, these agents were found to inhibit platelet aggregation induced in vitro in human platelet-rich plasma by the combination of ADP and serotonin. In view of the fact that serotonin is one of a variety of humoral factors capable of activating blood platelets and has been recently implicated as playing a role in certain thrombotic syndromes, encainide, along with its two principal human metabolites, ODE and MODE, and another class 1C antiarrhythmic, flecainide, were evaluated in an in vivo model of intravascular thrombosis. Intraduodenal doses of 1 mg/kg of either encainide, ODE, or MODE significantly inhibited thrombosis in a canine model of coronary artery stenosis-occlusion. PMID- 1909561 TI - Effect of the molsidomine metabolite SIN-1 on coronary arteries and peripheral vessels of sheep with special reference to tolerance and endothelium. AB - In vitro experiments on rings from coronary arteries, femoral arteries, and femoral veins of sheep were performed, and cumulative concentration-relaxation responses were established for glyceryl trinitrate (GTN) and the molsidomine metabolite SIN-1. Paired preparations of control and deendothelialized coronary artery rings were used, and the vessels were precontracted with different agonists at a concentration that elicited 30% of maximal contractions (EC-30). In coronary arteries, the responses for GTN and SIN-1 on normal and deendothelialized preparations were not significantly different. In coronary arteries preincubated with 0.44 mM GTN or SIN-1 to study tolerance development, there was a significant loss of efficacy to the relaxant effect of GTN, whereas the effect SIN-1 was essentially maintained. Femoral arteries and veins were readily relaxed with GTN. and SIN-1. In veins relaxation in relation to resting tone was much more pronounced than in coronary or femoral arteries. In conclusion, the molsidomine metabolite SIN-1 is a potent coronary and venous vasodilator that does not induce tolerance. PMID- 1909562 TI - rIL-4 differentially regulates rIL-2-induced murine NK and LAK killing in CD8+ and CD8- precursor cell subsets. AB - Interleukin 4 (IL-4) and IL-2 have complementary or synergistic roles in many aspects of lymphocyte development. IL-2 supports the induction of cytolytic activity in cytotoxic T lymphocyte (CTL), natural killer (NK), and lymphokine activated killer (LAK) cells. IL-4 has also been shown to support CTL and LAK in primary murine spleen cell culture. This report demonstrates that IL-4 selectively down-regulates IL-2 inducible murine CD8- precursors of NK cells. For maximal regulatory effect it is necessary to add IL-4 to cultures before 40 h. Enrichment for NK1.1+ cells failed to recover precursor cells which are down regulated in overnight cultures or can be cultivated in vitro to yield NK cytolytic activity. Furthermore, phenotypic analysis of effector cells demonstrated a marked inhibition of development of NK1.1+ cells in cultures containing IL-4 plus IL-2 versus IL-2 alone. Thus, it appears that IL-4 down regulates the precursors of murine NK cells by inhibiting proliferation and/or development. In addition, we show that IL-2-induced murine LAK activity mediated by CD8- precursor cells is unaffected by IL-4, while CD8(+)-derived LAK cells are up-regulated by co-culture with IL-4 and IL-2. Analysis of these data relative to reports documenting down-regulation of human LAK by IL-4 suggests that in vitro cultured, IL-2-activated murine NK cells are the correlates to what are commonly described as human LAK cells. The discrepancy may stem from differences in the characteristics of target cells used in the murine versus the human systems. These results clarify the conflicting reports on the effect of IL-4 on killing activity. PMID- 1909563 TI - Establishment of resistance to Leishmania major infection in susceptible BALB/c mice requires parasite-specific CD8+ T cells. AB - Although CD4+ T cells are generally accepted to be responsible for the determination of resistance to infection in experimental murine cutaneous leishmaniasis, a contribution of CD8+ lymphocytes to immunity can be demonstrated under certain well-defined conditions. Normally highly susceptible BALB/c mice can be rendered resistant to infection with Leishmania major promastigotes by a single injection of monoclonal anti-CD4 antibodies at the beginning of infection. Mice treated in such a way can heal their primary cutaneous lesions and acquire immunity to subsequent challenge infection. Both the resolution of the primary infection and the induced state of immunity to reinfection in these mice is shown to be dependent upon the anti-leishmanial effector functions of CD8+ T cells. Furthermore, in contrast to control infected BALB/c mice, which are unable to mount a delayed-type hypersensitivity (DTH) response to viable parasites, mice cured as a result of treatment with anti-CD4 antibodies in vivo exhibit a strong DTH response, which can be significantly reduced by injection of either anti-CD4 or anti-CD8 monoclonal antibodies prior to antigenic challenge with viable promastigotes. Moreover, increased numbers of specific CD8+ T cells, able to transfer Leishmania-specific DTH responses, were found in lymphoid organs of BALB/c mice rendered resistant to infection by immunointervention with anti-CD4 monoclonal antibodies at the beginning of infection. Neutralization in vivo of interleukin 4 during the course of infection in BALB/c mice also enables these otherwise susceptible mice to resolve their cutaneous lesions and to decrease the parasite burden in infected tissues. CD8+ T cells are required for both of these beneficial effects. Taken together, these results indicate that in the immune BALB/c mouse, as in the normally resistant CBA mouse, CD8+ lymphocytes are involved in the elimination of L. major and in the establishment and maintenance of immunity against infection with this parasite. PMID- 1909564 TI - Binding and cleavage of nucleic acids by the "hairpin" ribozyme. AB - The "hairpin" ribozyme derived from the minus strand of tobacco ringspot virus satellite RNA [(-)sTRSV] efficiently catalyzes sequence-specific RNA hydrolysis in trans (Feldstein et al., 1989; Hampel & Triz, 1989; Haseloff & Gerlach, 1989). The ribozyme does not cleave DNA. An RNA substrate analogue containing a single deoxyribonucleotide residue 5' to the cleavage site (A-1) binds to the ribozyme efficiently but cannot be cleaved. A DNA substrate analogue with a ribonucleotide at A-1 is cleaved; thus A-1 provides the only 2'-OH required for cleavage. These results support cleavage via a transphosphorylation mechanism initiated by attack of the 2'-OH of A-1 on the scissile phosphodiester. The ribozyme discriminates between DNA and RNA in both binding and cleavage. Results indicate that the 2'-OH of A-1 functions in complex stabilization as well as cleavage. The ribozyme efficiently cleaves a phosphorothioate diester linkage, suggesting that the pro Rp oxygen at the scissile phosphodiester does not coordinate Mg2+. PMID- 1909565 TI - Kinetic assay of fluorescein mono-beta-D-galactoside hydrolysis by beta galactosidase: a front-face measurement for strongly absorbing fluorogenic substrates. AB - A novel enzymatic assay method was developed for fluorogenic substrates that have significant intrinsic absorbance and fluorescence under the assay conditions. Fluorescein mono-beta-D-galactoside (FMG) was chosen as the substrate for the fluorescence enzymatic assay because of the high fluorescence of its hydrolytic product (fluorescein) and suitability of being hydrolyzed by beta-galactosidase. The fluorescence-concentration relationships for fluorescein and for FMG in both the right-angle detection mode of a fluorometer and the front-face detection mode of a fluorescence plate reader were exactly established and used to determine the kinetics of the enzyme assay. The results show that only front-face detection in the fluorescence plate reader can overcome the fluorescence concentration quenching that inevitably results from high absorbance by the intrinsically absorbing substrate in the conventional fluorometer, which utilizes right-angle detection. Only with front-face detection was the fluorescent assay of FMG hydrolysis under conditions of high optical density possible. The enzymatic measurements on the fluorescence plate reader were particularly efficient for determination of the enzyme kinetics because of the high rate of data collection. In this assay system, Michaelis-Menten constant Km and enzymatic catalysis rate k2 of FMG were determined as 117.6 microM and 22.7 mumol-(min.mg)-1, respectively. The results and methods described in this paper can be generalized for any assay using a fluorogenic substrate whether or not it has a high background absorbance. PMID- 1909566 TI - Kinetic fluorescence measurement of fluorescein di-beta-D-galactoside hydrolysis by beta-galactosidase: intermediate channeling in stepwise catalysis by a free single enzyme. AB - Kinetic fluorescence measurements were employed to quantitative to stepwise hydrolysis of fluorescein di-beta-D-galactoside (FDG) by beta-galactosidase and the intermediate fluorescein mono-beta-D-galactoside (FMG) channeling. The kinetic parameters, Michaelis-Menten constant Km and enzymatic catalysis rate k2, for FDG hydrolysis to FMG by beta-galactosidase were obtained as 18.0 microM and 1.9 mumol.(min-mg)-1, respectively. The FMG intermediate is hydrolyzed via two modes: (1) FMG that is in free solution binding to the enzyme substrate binding site in competition with FDG and then being hydrolyzed (binding mode); (2) FMG being directly hydrolyzed into the final products of fluorescein and galactose before the FMG can diffuse away from the enzyme active site (channeling mode). The extent of the FMG channeling mode was found to depend on the FDG hydrolysis rate but to be independent of the free enzyme concentration. A channeling factor, defined as the ratio of the real FMG hydrolysis rate with both binding and channeling modes over that which would be observed with an exclusive binding mode, was used to quantitate the effect of the intermediate channeling. The FMG channeling factor was determined to be close to 1 at low FDG concentration (about 5.1 microM), where the slow FDG hydrolysis rate gives an ineffective channeling and where the FMG is then hydrolyzed mainly via the binding mode. However, the channeling factor dramatically increases at higher FDG concentrations (greater than Km), strongly indicating that the effective FMG channeling mode, resulting from the considerable FDG hydrolysis rate at high FDG concentrations, becomes a primary pathway to channel a steady system hydrolysis with a high rate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1909567 TI - Identification of lysyl residues located at the substrate-binding site in UDP glucose pyrophosphorylase from potato tuber: affinity labeling with uridine di- and triphosphopyridoxals. AB - Uridine di- and triphosphopyridoxals were used to probe the substrate-binding site in potato tuber UDP-glucose pyrophosphorylase (EC 2.7.7.9). The enzyme was rapidly inactivated in time- and dose-dependent manners when incubated with either reagent followed by reduction with sodium borohydride. The inactivations were almost completely retarded by UDP-Glc and UTP but only slightly by alpha-D glucose 1-phosphate. The complete inactivation corresponded to the incorporation of about 0.9-1.0 mol of either reagent per mole of enzyme monomer. Both reagents appear to bind specifically to the UDP-Glc-(UTP)-binding site. Structural studies of the labeled enzymes revealed that the two reagents modified the identical set of five lysyl residues (Lys-263, Lys-329, Lys-367, Lys-409, and Lys-410), in which Lys-367 was most prominently modified. The ratios of the amounts of labels incorporated into these residues were similar for the two reagents. Furthermore, linear relationships were observed between the residual activities and the amounts of incorporation into each lysyl residue. We conclude that the five lysyl residues are located at or near the UDP-Glc(UTP)-binding site of potato tuber UDP Glc pyrophosphorylase and that the modification of these residues occurs in a mutually exclusive manner, leading to the inactivation of the enzyme. PMID- 1909568 TI - Expression in Escherichia coli of UDP-glucose pyrophosphorylase cDNA from potato tuber and functional assessment of the five lysyl residues located at the substrate-binding site. AB - The entire structural gene for potato tuber UDP-glucose pyrophosphorylase has been amplified from its cDNA by the polymerase chain reaction and inserted into the expression plasmid pTV118-N downstream from the lac promoter. Escherichia coli JM105 cells carrying thus constructed plasmid produced the enzyme to a level of about 5% of the total soluble protein upon induction with isopropyl beta-D thiogalactopyranoside. The recombinant enzyme purified to homogeneity in two column chromatographic steps was structurally and catalytically identical with the enzyme purified from potato tuber except for the absence of an N-terminal blocking acetyl group. To examine functional roles of the five lysyl residues that had been identified by affinity labeling studies to be located at or near the active site of the enzyme [Kazuta, Y., Omura, Y., Tagaya, M., Nakano, K., & Fukui, T. (1991) Biochemistry (preceding paper in this issue)], they were replaced individually by glutamine via site-directed mutagenesis. The Lys-367--- Gln mutant enzyme was almost completely inactive, and the Lys-263----Gln mutant enzyme had significantly decreased Vmax values with perturbed Km values for pyrophosphate and alpha-D-glucose 1-phosphate. Lys-329----Gln also exhibited increased Km values for these substrates but exhibited Vmax values similar to those of the wild-type enzyme. The two mutant enzymes Lys-409----Gln and Lys-410- --Gln showed catalytic properties almost identical with those of the wild-type enzyme. Thus, among the five lysyl residues, Lys-367 is essential for catalytic activity of the enzyme and Lys-263 and Lys-329 may participate in binding of pyrophosphate and/or alpha-D-glucose 1-phosphate. PMID- 1909569 TI - Mechanism of DNA polymerase alpha inhibition by aphidicolin. AB - Synthetic oligonucleotides of defined sequence were used to examine the mechanism of calf thymus DNA polymerase alpha inhibition by aphidicolin. Aphidicolin competes with each of the four dNTPs for binding to a pol alpha-DNA binary complex and thus should not be viewed as a dCTP analogue. Kinetic evidence shows that inhibition proceeds through the formation of a pol alpha.DNA.aphidicolin ternary complex, while DNase I protection experiments provide direct physical evidence. When deoxyguanosine is the next base to be replicated, Ki = 0.2 microM. In contrast, the Ki is 10-fold higher when the other dNMPs are at this position. Formation of a pol alpha.DNA.aphidicolin ternary complex did not inhibit the primase activity of the pol alpha.primase complex. Neither the rate of primer synthesis nor the size distribution of primers 2-10 nucleotides long was changed. Elongation of the primase-synthesized primers by pol alpha was inhibited both by ternary complex formation using exogenously added DNA and by aphidicolin alone. PMID- 1909570 TI - Subsite interactions of ribonuclease T1: viscosity effects indicate that the rate limiting step of GpN transesterification depends on the nature of N. AB - We report on the effect of the viscogenic agents glycerol and ficoll on the RNase T1 catalyzed turnover of GpA, GpC, GpU, and Torula yeast RNA. For wild-type enzyme, we find that the kcat/Km values for the transesterification of GpC and GpA as well as for the cleavage of RNA are inversely proportional to the relative viscosity of glycerol-containing buffers; no such effect is observed for the conversion of GpU to cGMP and U. The second-order rate constants for His40Ala and Glu46Ala RNase T1, two mutants with a drastically reduced kcat/km ratio, are independent of the microviscosity, indicating that glycerol does not affect the intrinsic kinetic parameters. Consistent with the notion that molecular diffusion rates are unaffected by polymeric viscogens, addition of ficoll has no effect on the kcat/Km for GpC transesterification by wild-type enzyme. The data indicate that the second-order rate constants for GpC, GpA, and Torula yeast RNA are at least partly limited by the diffusion-controlled association rate of substrate and active site; RNase T1 obeys Briggs-Haldane kinetics for these substrates (Km greater than Ks). Calculations suggest that the equilibrium dissociation constants (Ks) for the various GpN-wild-type enzyme complexes are virtually independent of N whereas the measured kcat values follow the order GpC greater than GpA greater than GpU. This is also revealed by the steady-state kinetic parameters of Tyr38Phe and His40Ala RNase T1, two mutants that follow simple Michaelis-Menten kinetics because of a dramatically reduced kcat value (i.e., Km = Ks).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1909571 TI - Characterization of the 25-kilodalton subunit of the energy-transducing NADH ubiquinone oxidoreductase of Paracoccus denitrificans: sequence similarity to the 24-kilodalton subunit of the flavoprotein fraction of mammalian complex I. AB - The NADH dehydrogenase complex isolated from Paracoccus denitrificans is composed of approximately 10 unlike polypeptides [Yagi, T. (1986) Arch. Biochem. Biophys. 250, 302-311]. Structural genes encoding the subunits of this enzyme complex constitute at least one gene cluster [Xu, X., Matsuno-Yagi, A., & Yagi, T. (1991) Biochemistry 30, 6422-6428]. The 25-kDa subunit (NQO2), which has been isolated from sodium dodecyl sulfate-polyacrylamide gels, is a polypeptide of this enzyme complex. The partial N-terminal amino acid sequence and amino acid composition of the NQO2 subunit have been determined. On the basis of the amino acid sequence, the NQO2 gene was found to be located 1.7 kilobase pairs upstream of the gene for NADH-binding subunit (NQO1). The complete nucleotide sequence of the NQO2 gene was determined. It is composed of 717 base pairs and codes for 239 amino acid residues with a calculated molecular weight of 26,122. The NQO2 subunit is homologous to the Mr 24,000 subunit of the mammalian mitochondrial NADH ubiquinone oxidoreductase which bears an electron paramagnetic resonance-visible binuclear iron-sulfur cluster (probably cluster N1b). Comparison of the predicted amino acid sequence of the Paracoccus NQO2 subunit with those of its mammalian counterparts suggests putative binding sites for the iron-sulfur cluster. In addition, nucleotide sequencing shows the presence of two unidentified reading frames between the NQO1 and NQO2 genes. These are designated URF1 and URF2 and are composed of 261 and 642 base pairs, respectively. The possible function of the protein coded for the URF2 is discussed. PMID- 1909572 TI - EcoRV restriction endonuclease binds all DNA sequences with equal affinity. AB - In the presence of MgCl2, the EcoRV restriction endonuclease cleaves its recognition sequence on DNA at least a million times more readily than any other sequence. In this study, the binding of the EcoRV restriction enzyme to DNA was examined in the absence of Mg2+. With each DNA fragment tested, several DNA protein complexes were detected by electrophoresis through polyacrylamide. No differences were observed between isogenic DNA molecules that either contained or lacked the EcoRV recognition site. The number of complexes with each fragment varied with the length of the DNA. Three complexes were formed with a DNA molecule of 55 base pairs, corresponding to the DNA bound to 1, 2, or 3 molecules of the protein, while greater than 15 complexes were formed with a DNA of 381 base pairs. A new method was developed to analyze the binding of a protein to multiple sites on DNA. The method showed that the EcoRV enzyme binds to all DNA sequences, including the EcoRV recognition site, with the same equilibrium constant, though two molecules of the protein bind preferentially to adjacent sites on the DNA in a cooperative fashion. All of the complexes with a substrate that contained the EcoRV site dissociated upon addition of competitor DNA, but when the competitor was mixed with MgCl2, a fraction of the substrate was cleaved at the EcoRV site. The fraction cleaved was due mainly to the translocation of the enzyme from nonspecific sites on the DNA to the specific site. PMID- 1909573 TI - Isolation, amino acid sequence, and synthesis of dermaseptin, a novel antimicrobial peptide of amphibian skin. AB - A 34-residue antimicrobial peptide named dermaseptin was purified to homogeneity from amphibian skin by a 3-step protocol involving molecular sieve filtration, ion-exchange chromatography, and reversed-phase high-performance liquid chromatography. The complete amino acid sequence of dermaseptin, ALWKTMLKKLGTMALHAGKAALGAAADTISQGTQ, was determined by automated Edman degradation of the peptide and of fragments generated by trypsin. Fast atom bombardment mass spectra of dermaseptin gave a protonated molecular ion m/z 3455.4 which matched the theoretical molecular weight predicted from the amino acid sequence. Dermaseptin was synthesized by the solid-phase method. The synthetic replicate was shown to be indistinguishable from natural dermaseptin with respect to chromatographic properties, amino acid sequence determination, and mass spectrometry analysis. Dermaseptin is a water-soluble, thermostable, and nonhemolytic peptide endowed with highly potent antimicrobial activity against pathogenic fungi at micromolar concentration. Circular dichroism spectra of dermaseptin in hydrophobic media indicated 80% alpha-helical conformation, and predictions of secondary structure suggested that dermaseptin can be configured as an amphiphatic alpha-helix spanning over residues 1-27, a structure that perturbs membrane functions regulating water flux. PMID- 1909574 TI - Complementing amino acid substitutions within loop 6 of the alpha/beta-barrel active site influence the CO2/O2 specificity of chloroplast ribulose-1,5 bisphosphate carboxylase/oxygenase. AB - Photosynthesis-deficient mutant 45-3B of the green alga Chlamydomonas reinhardtii contains a chloroplast mutation that causes valine-331 to be replaced by alanine within the large subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase. This amino acid substitution occurs in loop 6 of the alpha/beta-barrel active site, three residues distant from catalytic lysine-334. The mutation reduces the specific activity of the enzyme and also reduces its CO2/O2 specificity factor by 42%, but the amount of holoenzyme is unaffected. In a previous study, an intragenic-suppressor mutation, named S40-9D, was selected that causes threonine 342 to be replaced by isoleucine, thereby increasing the CO2/O2 specificity of the mutant enzyme by 36%. To determine which other residues might be able to complement the original mutation, nine additional genetically independent revertants have now been analyzed. Another intragenic suppressor, represented by mutation S61-2J, causes glycine-344 to be replaced by serine. This change increases the CO2/O2 specificity of the mutant enzyme by 25%. Of the revertants recovered and analyzed, the mutant enzyme was improved only due to true reversion or by intragenic suppression mediated by substitutions at residues 342 or 344. Changes in the physical properties of the two pairs of complementing substitutions indicate that steric effects within loop 6 are responsible for the observed changes in the CO2/O2 specificity of the enzyme. PMID- 1909576 TI - Structure-function relationships in human epidermal growth factor studied by site directed mutagenesis and 1H NMR. AB - In order to elucidate the mechanism of interaction between human epidermal growth factor (EGF) and its receptor, selected variants of EGF, differing by single amino acid substitutions, have been made by site-directed mutagenesis. The receptor affinity of these mutants was determined by a receptor binding competition assay, and the effects of the substitution on the structure of the protein were assessed by 1H nuclear magnetic resonance techniques. Various substitutions of Arg-41 resulted in substantial reduction in receptor affinity of EGF whereas change of Tyr-13 did not affect binding to the receptor. The 1H resonances of all nonexchangeable protons of the Tyr-13----Leu, Arg-41----His, and Leu-47----Glu variants were assigned and compared in order to assess the structural integrity of these mutants, which possess very different spectral and biological properties. In the case of the Leu-47----Glu mutant, only minor localized spectral changes were observed, confirming that the tertiary structure of the protein is preserved upon mutation. In contrast, for both the Arg-41--- His and Tyr-13----Leu variants, significant and strikingly similar spectra changes were observed for many residues located far away from the mutated residues. This implies that similar structural alterations have taken place in both proteins, an idea further supported by hydrogen-exchange experiments where the exchange rates of hydrogen-bonded amide protons for both the Tyr-13----Leu and the Arg-41----His mutants were found to be about 4 times faster than in the wild-type protein.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1909575 TI - An active-site lysine in avian liver phosphoenolpyruvate carboxykinase. AB - The participation of lysine in the catalysis by avian liver phosphoenolpyruvate carboxykinase was studied by chemical modification and by a characterization of the modified enzyme. The rate of inactivation by 2,4-pentanedione is pseudo-first order and linearly dependent on reagent concentration with a second-order rate constant of 0.36 +/- 0.025 M-1 min-1. Inactivation by pyridoxal 5'-phosphate of the reversible reaction catalyzed by phosphoenolpyruvate carboxykinase follows bimolecular kinetics with a second-order rate constant of 7700 +/- 860 M-1 min-1. A second-order rate constant of inactivation for the irreversible reaction catalyzed by the enzyme is 1434 +/- 110 M-1 min-1. Treatment of the enzyme with pyridoxal 5'-phosphate gives incorporation of 1 mol of pyridoxal 5'-phosphate per mole of enzyme or one lysine residue modified concomitant with 100% loss in activity. A stoichiometry of 1:1 is observed when either the reversible or the irreversible reactions catalyzed by the enzyme are monitored. A study of kobs vs pH suggests this active-site lysine has a pKa of 8.1 and a pH-independent rate constant of inactivation of 47,700 M-1 min-1. The phosphate-containing substrates IDP, ITP, and phosphoenolpyruvate offer almost complete protection against inactivation by pyridoxal 5'-phosphate. Modified, inactive enzyme exhibits little change in Mn2+ binding as shown by EPR. Proton relaxation rate measurements suggest that pyridoxal 5'-phosphate modification alters binding of the phosphate containing substrates. 31P NMR relaxation rate measurements show altered binding of the substrates in the ternary enzyme.Mn2+.substrate complex. Circular dichroism studies show little change in secondary structure of pyridoxal 5' phosphate modified phosphoenolpyruvate carboxykinase. These results indicate that avian liver phosphoenolpyruvate carboxykinase has one reactive lysine at the active site and it is involved in the binding and activation of the phosphate containing substrates. PMID- 1909577 TI - Biological activity of a fluorescein human growth hormone derivative prepared by specific covalent labeling of lysine-70. AB - Modification of human growth hormone (hGH) with a low equimolar concentration of fluorescein isothiocyanate (FITC) yielded a derivative containing 1 mol of fluorescein/mol of protein. The site of modification was identified as lysine-70. Lysine-70 of hGH is about 3-fold more reactive than a "normal" lysine in a protein, having pseudo-first-order kinetics Kobs = 110 +/- 7 M-1 min-1 at pH 10.5. The pKa of the lysine was estimated to be 10.7, within the normal range of normal epsilon-lysine moieties in proteins. This higher chemical reactivity seems to favor selective labeling of this moiety at low FITC concentrations. To obtain monomodified derivatives, hGH was derivatized with 0.6 equiv of FITC, and the modified derivatives were separated from unreacted hormone by means of HPLC using a Mono Q column. Its biological activity, determined by Nb2 bioassay, decreased to 40%, and its affinity toward lactogen receptors in Nb2 cells and toward somatogen receptors in bovine liver decreased respectively to 30% and 20%. The present study indicates that out of the seven amino groups of human growth hormone, the epsilon-amino group of lysine-70 is excessively reactive toward FITC. Second, this particular amino group contributes to receptor binding and receptor activation. Lysine-70 is located in the loop between the first and second helix and close to the carboxy-terminal end of the first helix. This contribution is most likely the result of the formation of an electrostatic interaction between the hormone and the receptor.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1909578 TI - Purification and characterization of the hemorrhagic factor II from the venom of the Bushmaster snake (Lachesis muta muta). AB - Hemorrhagic factor II (LHF-II) was isolated from Lachesis muta muta (Bushmaster snake) venom using column chromatographies on Sephadex G-100, CM-Sepharose CL-6B and two cycles on Sephadex G-50. This preparation was devoid of phospholipase A2 as well as of the enzymes active on arginine synthetic substrates (TAME and BAPNA) which are present in the crude venom. LHF-II was homogeneous by SDS polyacrylamide gel electrophoresis, immunodiffusion and immunoelectrophoresis. Also, a single symmetrical boundary with a value of 2.59 S was obtained by ultracentrifugation. LHF-II contains 180 amino acid residues, has a molecular weight of 22,300, and an isoelectric point of 6.6. It contains one gatom zinc and two gatoms calcium per mol protein. The hemorrhagic factor possesses proteolytic activity toward various substrates such as, casein, dimethylcasein, hide powder azure, fibrinogen and fibrin. It hydrolyzes selectively the A alpha-chain of fibrinogen, leaving the B beta- and gamma-chains unaffected. LHF-II is activated by Ca2+ and inhibited by Zn2+. The hemorrhagic as well as the proteinase activity is inhibited by cysteine and by metal chelators such as EDTA, EGTA and 1,10 phenanthroline. Inhibitors of serine proteinases such as phenylmethanesulfonyl fluoride (PMSF) and soybean trypsin inhibitor (SBTI) have no effect on the hemorrhagic factor. PMID- 1909579 TI - Penicillium chrysogenum extracellular acid phosphatase: purification and biochemical characterization. AB - An extracellular acid phosphatase (EC 3.1.3.2) from crude culture filtrate of Penicillium chrysogenum was purified to homogeneity using high-performance ion exchange chromatography and size-exclusion chromatography. SDS-PAGE of the purified enzyme exhibited a single stained band at an Mr of approx. 57,000. The mobility of the native enzyme indicated the Mr to be 50,000, implying that the active form is a monomer. The isoelectric point of the enzyme was estimated to be 6.2 by isoelectric focusing. Like acid phosphatases from several yeasts and fungi the Penicillium enzyme was a glycoprotein. Removal of carbohydrate resulted in a protein band with an Mr of 50,000 as estimated by SDS-PAGE, suggesting that 12% of the mass of the enzyme was carbohydrate. The enzyme was catalytically active at temperatures ranging from 20 degrees C to 65 degrees C with a maximum activity at 60 degrees C and the pH optimum was at 5.5. The Michaelis constant of the enzyme for p-nitrophenyl phosphate was 0.11 mM and it was inhibited competitively by inorganic phosphate (ki = 0.42 mM). PMID- 1909580 TI - Recent investigations into the lipoxygenase pathway of plants. AB - The plant lipoxygenase (LOX) pathway is in many respects the equivalent of the 'arachidonic acid cascade' in animals. The LOX-catalyzed dioxygenation of the plant fatty acids, linoleic and linolenic acids, is followed by metabolism of the resulting fatty acid hydroperoxides by other enzymes. Although the physiological functions of the end-products do not appear to be fully defined at this time, hormonal and anti-fungal activities have been reported. PMID- 1909581 TI - Differential silver enhanced double labeling in immunoelectron microscopy. AB - A two-sided double labeling method using protein A gold was used to demonstrate the presence of two hormones within the same anterior pituitary cell granule. A single probe size was used for both section faces but one side of the grid was silver enhanced. The use of a single probe size reduced the cost of the study and eliminated the variations in labeling efficiency that result from the use of different probe sizes. PMID- 1909582 TI - In vivo characteristics of high molecular weight copoly(L-lactide/glycolide) with S-type degradation pattern for application in drug delivery systems. AB - Amorphous copoly(L-lactide)/glycolide, 70/30 mol%) with weight average molecular weights of 16,900-41,300 were synthesized by ring-opening polymerization in the presence of catalysts using a molecular weight moderator lauryl alcohol. The in vivo degradation profiles of the copolyesters, which were evaluated by implanting them subcutaneously in the back of rats, showed a typical S-type degradation pattern. A luteinizing hormone-releasing hormone agonist (LH-RH agonist), des Gly10-[Leu6]-LH-RH ethylamide monoacetate, was incorporated into the small cylinders of copoly (L-lactide/glycolide) with a weight average molecular weight of 24,000. The cumulative amount of drug released in vivo from the cylinders showed an S-type profile in analogy with the in vivo degradation pattern. This was demonstrated from data such as serum drug level and pharmacological influence on rat prostates. PMID- 1909583 TI - Long-term effects of elemental and exclusion diets for Crohn's disease. AB - Previous studies have confirmed the therapeutic value of elemental diets in promoting remission in active Crohn's disease, but their long-term benefit has not been established. Twenty-seven patients with established Crohn's disease who attained clinical remission after four weeks of enteral feeding were followed prospectively for up to 36 months. Twenty of these were willing to be tested for specific food intolerance using a pre-defined dietary elimination protocol; the others continued on a normal unrestricted diet. Eighteen patients (67%) have since relapsed; 89% of the relapse occurred within the first 6 months. Of the 15 patients with colonic involvement, 12 (80%) relapsed by 6 months. In contrast only 3 of 11 with isolated small bowel disease experienced early relapse. Of the 14 patients who completed the process of dietary testing, 5 could not identify any trigger foods; the remaining 9 were maintained on exclusion diets, 3 of whom relapsed early. Of the 11 taking a normal diet, 9 relapsed. Disease duration, previous intestinal resection or prior steroid therapy did not affect the relapse rate. Eight patients (31%) obtained a long-term remission, mean 23 months (range 12-36 months), without any medication. Long-lasting remissions can be obtained in about one-third of patients with Crohn's disease following treatment with a defined formula diet. Colonic involvement is associated with a high early relapse rate. PMID- 1909585 TI - Review article: dietary and nutritional management of Crohn's disease. AB - The value of dietary alteration and the nutritional management of Crohn's disease is assessed in this review. Lactose restriction, low-fat diets and low-residue diets may be of value in specifically indicated clinical situations. A fibre rich, unrefined carbohydrate diet has not been shown to alter the course of the disease, and the value of 'exclusion diets' remains to be confirmed in controlled, prospective studies. Nutritional insufficiency of varying degrees is common in Crohn's disease and can be corrected by the efficient use of enteral diets (usually with polymeric preparations) or intravenous nutritional support. Growth retardation in adolescents with Crohn's disease can usually be improved by enteral nutrition. Nutritional support of various kinds may be of value in the management of local complications of Crohn's disease; sub-acute obstruction, anal, perianal and rectal lesions, fistulas and ileostomy complications, and the management of bile acid-induced diarrhoea. The use of nutrition as 'primary therapy; in Crohn's disease is considered. Theoretical reasons why nutritional support and bowel rest may possibly induce remission of the disease are discussed. The evidence to date suggests that intravenous nutrition and bowel rest may not be effective in inducing a primary remission of the disease, and the possible value of elemental diets and polymeric diets in this respect are assessed. Further prospective controlled studies of elemental diets as primary therapy in Crohn's disease are required. PMID- 1909584 TI - Efficacy of misoprostol and ranitidine in the prevention of duodenal ulcer relapse and its correlation with endogenous gastric prostanoid synthesis. AB - We determined endogenous gastric prostaglandin synthesis and its correlation with the prevention of duodenal ulcer relapse by misoprostol and ranitidine. Sixty-one patients with recent endoscopically healed duodenal ulcer were randomly allocated in a double-blind fashion for one year of treatment with misoprostol 400 micrograms nocte, ranitidine 150 mg nocte or placebo. Patients were followed every two months. Endoscopy was repeated at six and 12 months or beforehand, if relapse was suspected. Antral and fundic biopsies, 3-4 from each region, were obtained at each endoscopy for determination of prostaglandin synthesis. During the one year of treatment, 11 out of the 12 placebo treated patients flared up, as opposed to 10 out of 25 and four out of 24 misoprostol and ranitidine treated patients, respectively. The difference between all treatment groups was significant (P less than 0.0001). In all subjects who flared up, pretrial endogenous antral and fundic prostaglandin E2 synthesis were not different from their respective synthesis in those who did not relapse. PMID- 1909586 TI - Maintenance therapy for peptic ulcer disease. AB - Peptic ulcers tend to recur; recurrence may be associated with an increased risk of potentially lethal complications, such as haemorrhage or perforation. Therapy aims to keep ulcers in remission. Currently, the optimal maintenance therapy is long-term, continuous administration of antisecretory drugs. More than 80% of patients remain in remission during maintenance therapy. Maintenance therapy may be required for the life of the patient, but it is acceptable to patients and is safe. PMID- 1909587 TI - Peyer's patch B cells with memory cell characteristics undergo terminal differentiation within 24 hours in response to interleukin-6. AB - Culture of Peyer's patch (PP) B cells with interleukin-6 (IL-6) for 7 days results in a six- to eightfold increase in secretion of IgA, while little or no increase in IgM or IgG secretion occurs in these cultures. Further, greater than 80% of IgA is produced within the first 72 h of culture. Using a sensitive enzyme linked immunospot (ELISPOT) assay, we have shown that culture of PP B cells with IL-6 for 24 h gave increased IgA spot-forming cells (SFC) (4- to 6- fold) even though secreted IgA, as measured by RIA, had only increased 1.6- to 2.0-fold. In addition, significant increases in IgA SFC numbers could be demonstrated as early as 4 h after addition of IL-6. The increase in IgA secretion was not the result of IL-6-induced B-cell proliferation, since culture of B cells with IL-6 resulted in no increase in [3H]thymidine incorporation compared to untreated controls. This was supported by studies with mitomycin C which, when added to B cell cultures, had no effect on the IL-6-induced increase in numbers of IgA SFC. Increased IgA secretion was totally abolished by actinomycin D, an inhibitor of RNA transcription, showing that continued production of alpha mRNA is essential for IL-6-induced IgA secretion. Separation of PP B cells into peanut agglutin (PNA)Hi (germinal center [GC]) and PNALo (non-GC) subpopulations before culture with IL-6 showed that only PNALo B cells transcribe increased levels of alpha mRNA message and secrete high levels of IgA in response to this cytokine. Although the GC are the site of B-cell proliferation and presumably of switching to IgA and contain 70 to 85% of sIgA+ B cells in the PP, these PNAHi B cells do not respond to IL-6. This suggests that memory sIgA+ B cells in PP express IL-6 receptor (IL-6R) and respond to this cytokine with rapid differentiation into plasma cells that secrete IgA. PMID- 1909588 TI - Murine interferon-gamma/interleukin-1 fusion proteins used as antigens for the generation of hybridomas producing monoclonal anti-interleukin-1 antibodies. AB - In several biological systems interferon-gamma (IFN-gamma) and interleukin-1 (IL 1) act synergistically. We therefore examined whether it would be possible to construct IFN-gamma/IL-1 hybrid proteins that would be more active than the individual components. Hybrid proteins were examined that consisted of the amino terminal 118 residues of mouse IFN-gamma and the 156 or 152 carboxyl-terminal residues of mouse IL-1 alpha or IL-1 beta, respectively. They were obtained by ligation of the respective coding sequences and expression of the fused genes under control of the PL promotor in Escherichia coli. Both the IFN-gamma/IL-1 alpha and the IFN-gamma/IL-1 beta fusion proteins were purified by affinity chromatography on an anti-IFN-gamma monoclonal antibody column. Analysis of biological activities showed that these fusion proteins were less active than the individual cytokines. Specific antiviral activity of the IFN-gamma/IL-1 beta hybrids was less than 0.1% that of IFN-gamma and D10.G4.1 T-cell proliferative (IL-1) activity amounted to 0.1% that of mouse IL-1. Affinity-purified preparations of the IFN-gamma/IL-1 alpha hybrid were found to contain variable proportions of a Mr 14,000 degradation product possessing IFN-gamma activity, whereas the undegraded Mr 30,000 fusion protein, while being devoid of detectable IFN-gamma activity, did possess IL-1 activity (1%). Serum from rats immunized with the IFN-gamma/IL-1 alpha hybrid contained high levels of IL-1 alpha-binding and -neutralizing antibodies and IFN-gamma-binding antibodies, but no detectable levels of IFN-gamma-neutralizing antibodies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1909589 TI - Suppression of bacterial cell wall-induced polyarthritis by recombinant gamma interferon. AB - Group A streptococcal cell wall fragments (SCW) induce erosive polyarthritis, characterized by synovial cell hyperplasia and intense mononuclear cell infiltration, in susceptible rats. Because of the known antiproliferative and immunomodulatory effects of interferon (IFN), we evaluated the effect of systemically administered alpha, beta and gamma IFN on the evolution of these destructive lesions. Treatment with gamma IFN not only reduced the acute response, but had an even greater suppressive effect on the chronic mononuclear cell-mediated destructive phase of the disease (articular index 10.2 +/- 1.2 for SCW only versus 3.8 +/- 0.7 for SCW + gamma IFN; p less than 0.01). Treatment with gamma IFN was more effective in the suppression of the arthritis than alpha, beta IFN. Histopathologic evaluation of the joints demonstrated that gamma IFN treated animals had significantly fewer inflammatory cells, and less synovial hyperplasia and erosions than the SCW controls. gamma IFN suppression of mononuclear cell prostaglandin synthesis and synovial fibroblast proliferation was consistent with its anti-arthritic effects. These data indicate that the pathophysiology of SCW-induced erosive polyarthritis is subject to regulatory control by gamma IFN and that the mechanisms of suppression may be relevant in the treatment of rheumatoid arthritis. PMID- 1909590 TI - Normal and lysine-containing zeins are unstable in transgenic tobacco seeds. AB - Chimeric genes composed of the beta-phaseolin promoter, an alpha-zein coding sequence and its modified versions containing lysine codons, and a beta-zein polyadenylation signal were inserted into the genome of tobacco by Agrobacterium mediated transformation. alpha-Zein mRNA levels in the transgenic tobacco seeds 20 days after self-pollination varied between 1.0% and 2.5% of the total mRNA population. At 25 days after pollination the 19 kDa alpha-zein was immunologically detected with a polyclonal antiserum in protein extracts from the seeds of transgenic plants. The transgenic plant with the highest level of zein gene expression had an alpha-zein content that was approximately 0.003% of the total seed protein. The amount of alpha-zein in other transgenic plants varied between 1 x 10(-4)% and 1 x 10(-5)% of the total seed protein. The differences in the amounts of mRNA and protein did not correlate with the lysine substitutions introduced into the alpha-zein protein. Polysomes translating alpha-zein mRNA isolated from tobacco seeds contained fever ribosomes than those from maize endosperm, but this did not appear to be the cause of the inefficient protein synthesis. In vivo labelling and immunoprecipitation indicated that newly synthesized alpha-zein was degraded in tobacco seeds with a half-life of less than 1 hour. PMID- 1909591 TI - cDNA cloning and characterization of a putative 1,3-beta-D-glucanase transcript induced by fungal elicitor in bean cell suspension cultures. AB - Synthetic oligonucleotides based on similarity between tobacco 1,3-beta-D glucanase and barley 1,3-1,4-beta-D-glucanase were used to prime the synthesis and amplification of a 162 bp bean (Phaseolus vulgaris L.) beta-glucanase cDNA by the polymerase chain reaction (PCR). The PCR product was used to isolate a near full-length beta-glucanase cDNA corresponding to an approximately 1400 bp full length transcript, from a library containing cDNA sequences complementary to mRNA from fungal elicitor-treated bean cells. At the amino acid level, the bean beta glucanase cDNA was 59% similar to tobacco 1,3-beta-D-glucanase, 46% similar to barley 1,3-beta-D-glucanase and 46% similar to barley 1,3-1,4-beta-D-glucanase. At the nucleotide level, the similarities were 65, 50 and 53% respectively. The beta-glucanase appeared to be encoded by a single gene with similar genomic organization in bean cultivars Canadian Wonder, Imuna and Saxa. On the basis of predicted Mr, isoelectric point, sequence similarity, and comparisons of rate of transcript appearance with induced enzyme activity, it was concluded that the cDNA encodes the basic bean endo-1,3-beta-D-glucanase. Glucanase transcripts were induced, from very low basal levels, with similar kinetics to chitinase transcripts in elicitor-treated bean cell suspension cultures. PMID- 1909593 TI - The lymphocyte-specific tyrosine protein kinase p56lck. AB - The CD4 and CD8 T cell surface antigens are physically associated with the tyrosine protein kinase p56lck. Accumulating data indicate that p56lck transduces intracellular tyrosine protein phosphorylation signals upon engagement of CD4 and CD8 by major histocompatibility complex (MHC) determinants expressed on antigen presenting cells (APCs). Recent studies show that these p56lck-related phosphorylation events enhance T cell receptor (TCR)-mediated functions and are critical for the proposed co-receptor roles of CD4 and CD8. p56lck is also capable of enhancing antigen receptor responsiveness in the absence of CD4 or CD8 expression, suggesting that it can directly contribute to the TCR-induced tyrosine phosphorylation signal. PMID- 1909592 TI - The roles of CD4 and CD8 in T cell activation. AB - CD4 and CD8 T cell surface molecules play a role in T cell recognition and activation by binding to their respective class II and class I major histocompatibility complex (MHC) ligands on an antigen presenting cell (APC). Though CD4 and CD8 are capable of binding to MHC molecules in the absence of the T cell receptor (TCR), increasing evidence suggests that they may primarily function by complexing with the TCR to form a 'co-receptor' for recognition of antigen-bound MHC. Using gene transfer studies we have demonstrated that CD4 and CD8 can augment antigen-induced IL-2 production through different mechanisms dependent on whether or not they can bind MHC independently of the TCR or complexed with the TCR. Under circumstances where CD4 and CD8 can bind to the same MHC ligand as the TCR, they potentiate antigen-induced IL-2 production maximally by a mechanism in large part dependent on their cytoplasmic tails. Enhancement of antigen-induced IL-2 production can also occur under circumstances where CD4 and CD8 bind on MHC ligand distinct from that recognized by the TCR. In this instance, the magnitude of this enhancement is not as great and appears (at least for CD8) to be independent of the cytoplasmic tail and the associated p56lck. The dependence of co-receptor function on the cytoplasmic tail of CD4 or CD8 may reflect the activity of the associated intracellular tyrosine kinase p56lck.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1909594 TI - CD4 and CD8 act as co-receptors during thymic selection of the T cell repertoire. AB - The selection of T cell receptor specificities must logically not only involve the alpha beta-TCR but, also the CD4 and CD8 molecules, as antigen recognition by the alpha beta-TCR on mature T cells is facilitated by the CD4 and CD8 co receptors. In this review, the studies that provided key advances in our understanding of the possible role of CD4 and CD8 in T cell development will be discussed. PMID- 1909595 TI - CD4 and CD8 recognition of class II and class I molecules of the major histocompatibility complex. AB - T cells recognize their specific antigen when associated to the class I or class II molecules of the major histocompatibility complex (MHC). The T cell receptors, the effector molecules of specific antigen recognition are selected to have low affinity for self MHC molecules. Other molecules have been shown to play a major role in stabilizing the interaction between the TCR, self MHC and antigen. This review will focus on two of these molecules, namely CD4 and CD8. In contrast to other accessory molecules, the ligands of CD4 and CD8 are the same MHC molecules which are recognized by the T cell receptor. The structural analysis of the interaction between CD8, CD4 and their respective ligands, namely class I and class II molecules of the MHC, will be treated in this review. We will also discuss the possible differences which exist in the interaction of CD4 and CD8 with their respective ligands. PMID- 1909596 TI - [Health benefits of exercise and its cost-effectiveness]. AB - It is common to argue for sport and physical activity with its health benefits. There has also been a growing demand for using sport as a method for health promotion and preventive care. The effects of sport and physical activity are known to same extend. We know some individual effects of sport to blood circulation and hypertension and so on. What we actually do not know, is, whether sport is a good and effective remedy for illnesses or in health promotion when compared with other possible treatments. And if it is, is it also cost-effective? Also there is no evidence of possibilities of cutting down health care costs by encouraging our population to make more sport and physical training. PMID- 1909597 TI - The Clerkenwell scheme: assessing efficacy and cost of a psychiatric liaison service to a magistrates' court. AB - OBJECTIVE: To determine the efficacy of psychiatric liaison schemes to magistrates' courts in shortening the period that mentally ill accused people spend in custody between arrest, the provision of psychiatric reports, and admission to hospital under the Mental Health Act 1983 and to establish the direct costs of setting up such schemes. DESIGN: A nine month prospective study of court referrals and concurrent analysis of prison records. SETTING: An inner London magistrates' court (Clerkenwell) and a large remand prison (Brixton). PATIENTS: Consecutive series of 80 remand prisoners receiving psychiatric assessment through a liaison scheme; 50 remand prisoners placed on hospital orders by magistrates' courts after being remanded to prison for reports; 364 psychiatric prisoners undergoing second opinion assessments at a remand prison; 520 offenders in a remand prison placed on hospital orders. MAIN OUTCOME MEASURES: Comparison of lengths of time spent in custody for different stages of the assessment and disposal process. RESULTS: For the 50 remand prisoners assessed in prison the mean time from arrest to appearance in court with a psychiatric report was 33.7 days and from arrest to admission to hospital 50.8 days. For those examined in court under the liaison scheme the equivalent figures were 5.4 days (t = 12.63, p less than 0.0001) and 8.7 days (t = 13.04, p less than 0.0001). The number of hospital orders made at the court increased fourfold after the liaison scheme began. The additional direct costs of the scheme were negligible. CONCLUSION: Psychiatric liaison services to magistrates' courts can greatly reduce the length of time that offenders with mental disorders spend in custody. Such schemes may increase recognition of offenders suitable for admission to hospital. A scheme could be established in some areas within existing service provision. PMID- 1909599 TI - Case management. AB - "This paper discusses the advantages and disadvantages of case management systems for the co-ordination of care of people with long-term mental illness living in the community. Many of the principles are equally applicable to other client groups with long-term needs, e.g. elderly people or people with learning difficulties. Some of the historical background to the emergence of case management concepts is discussed, culminating in the recent White Paper on Community Care. The underlying concept of case management is examined, together with a number of fundamental questions concerning who should act as case managers, what kinds of training they will require, problems of inter- and intra agency co-operation, and the empirical evidence regarding its effectiveness. It is concluded that case management could be an important element in a comprehensive range of mental health services, but it is not a substitute for basic community provisions." PMID- 1909598 TI - Medical high-technology assessment and implementation in a community hospital: nuclear magnetic resonance. AB - Health care administrators and physicians are under intense pressure from the government, industry, and the public at large to contain the escalating cost of health care. Operating margins of hospitals are averaging about 1%, and some hospitals are closing their doors. Health care providers are thus faced with the dilemma of how to bring costly high technology to a community hospital in a timely and effective manner without incurring serious financial setbacks. Despite all these pressures, we have presented several reasons why a community hospital should bring costly technology to its medical staff, and thus to its patients. We have described Kettering Medical Center's approach to this problem and our success in bringing it to the community early and cost-effectively, which has benefited the local community as well as the medical center. Our desire to be one of the "early adopters" may not work for everyone, since it requires extremely careful and perceptive evaluation of the technologic developments. It requires an intelligent, progressive, and committed board, administration, and medical staff, and it requires clever financing, such as large outside grants and help from a medical school. Such partnerships and research organizations, or liaisons with government agencies such as the Veterans Affairs system, are believed to be the keys in getting costly high technology into a community hospital. To achieve this, administration and key medical staff should constantly be on the lookout, evaluating high-technology developments. Once the hospital decides to get into a costly new high technology, it must seek alliances or partnerships with others. To identify, assess, and acquire new technology is an ongoing process.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1909600 TI - Rat olfactory neurons express a 200 kDa neurofilament. AB - Neurofilament expression in peripheral olfactory neurons of adult rats was investigated by immunoblotting and immunohistochemistry using monoclonal antibodies specific for each of the 3 neurofilament proteins. Immunoblotting analysis of olfactory epithelium extracts demonstrated the presence of only the 200 kDa (NFH) polypeptide; the 68 kDa (NFL) and 160 kDa (NFM) neurofilaments were not detected. Similarly, no immunoreactivity was observed in tissue sections using the NFL and NFM antibodies. In contrast, when sections were probed with the antibody to NFH, immunoreactivity was localized primarily in the dendritic knobs and near the cell bodies of the receptor cells. PMID- 1909602 TI - Listeria monocytogenes CAMP reaction. PMID- 1909601 TI - An evaluation of selected screening tests for bovine paratuberculosis. AB - The objective of this study was to evaluate the performance of the lipoarabinomannan antigen enzyme-linked immunosorbent assay (LAM-ELISA), carbohydrate antigen complement fixation (CH-CFT), and protein D antigen agar gel immunodiffusion (D-AGID) tests for bovine paratuberculosis, relative to histopathology, and to culture and isolation of Mycobacterium paratuberculosis from tissues and feces. Samples for test evaluation were collected from four sources including blood and tissues from 400 cull cows at three abattoirs in Ontario, blood and feces from a paratuberculosis survey of cattle from 120 dairy farms in Ontario, a serum bank containing samples from cattle from Ontario and Quebec, and a bank of sera from cattle from Pennsylvania and the northeastern United States. The data were analyzed using receiver operator characteristic curves, estimates of relative sensitivity and specificity, and kappa statistics of agreement between tests. The LAM-ELISA performed significantly better than both the CH-CFT and the D-AGID tests. The LAM-ELISA was better at predicting fecal shedding status than tissue infection. However, the LAM-ELISA also had limitations. When interpreted as positive or negative (+/-), at a critical optical density of 0.675, its sensitivity and specificity relative to bacteriology were 49% and 87% respectively. Although the serological tests examined in this study provided some information, they did not predict well the infection status of individual animals. PMID- 1909603 TI - Dihydroergokryptine versus dihydroergotamine in migraine prophylaxis: a double blind clinical trial. AB - Dihydroergokryptine has been evaluated in the prophylaxis of headache attacks in patients with migraine without aura. The study was controlled vs dihydroergotamine with a double-blind crossover design. After a 1-month run-in period, 30 patients were randomized into two groups and submitted to 4 months treatment with dihydroergokryptine 10 mg b.i.d. or dihydroergotamine (controlled release) 5 mg b.i.d. The treatment was repeated in crossover after 2 months washout. The clinical patients' evaluation was determined by monthly Pain Total Index recording, headache days/month and analgesic consumption. The patients were considered responsible when Pain Total Index decreased by 50% or more in 1 or more months of each treatment period; otherwise the patients were considered unresponsive. The response rate to dihydroergokryptine was 66% while 48% of cases were responsive to dihydroergotamine. The response rate to both treatments was 41%, while 26% did not respond to either treatment. Seven cases unresponsive to dihydroergotamine responded positively to dihydroergokryptine while two cases only, resistant to dihydroergokryptine, responded positively to dihydroergotamine. Three cases dropped out during treatment with dihydroergotamine due to gastric pain and nausea, while they did not show any side effects during dihydroergokryptine therapy. During treatment with dihydroergokryptine there was one case of skin rash which disappeared after drug withdrawal. In conclusion, dihydroergokryptine appears to be an effective drug for the prophylaxis of migraine attacks. PMID- 1909604 TI - Coronary occlusion following diagnostic angiography: salvage by intracoronary stenting. AB - Catheter-induced coronary artery dissection and occlusion is a rare but serious complication of diagnostic cardiac angiography. This report describes the successful management of this complication with an intracoronary stent after prolonged balloon inflations and intracoronary thrombolytic therapy were unsuccessful. PMID- 1909605 TI - Mice lacking MHC class II molecules. AB - We have produced mice that lack major histocompatibility complex class II antigens, permitting us to evaluate the role of these molecules in diverse aspects of T and B cell differentiation. The mutant mice show near-complete elimination of CD4+ T lymphocytes from the spleen and lymph nodes; the few remaining CD4-positive cells are preferentially localized to B cell follicles. Surprisingly, substantial numbers of CD4 single-positive cells reside in the thymus; however, these are not mature thymocytes as we currently recognize them. B lymphocytes occur in normal numbers and are capable of terminal differentiation to plasma cells. Nevertheless, several aberrations in the B cell compartment are demonstrable: a lack of germinal centers, fewer IgM+IgD+ cells in certain individuals, reduced production of serum IgG1, and complete inability to respond to T-dependent antigens. In short, the class II-negative mice have confirmed some old ideas about lymphocyte differentiation, but have provided some surprises. PMID- 1909606 TI - Basolateral sorting in MDCK cells requires a distinct cytoplasmic domain determinant. AB - In MDCK cells, Golgi to basolateral transport of several membrane proteins has been found to involve a cytoplasmic domain determinant. In some cases (Fc receptor, lysosomal glycoprotein Igp120), the determinant appears similar to that required for endocytosis via clathrin-coated pits; for Igp120, elimination of a single cytoplasmic domain tyrosine both blocks internalization and results in apical transport. In other cases (LDL receptor), the determinant does not involve the cytoplasmic domain tyrosine required for endocytosis. Thus, contrary to current models, basolateral transport in MCDK cells occurs not by default but depends on one or more cytoplasmic domain determinants, the precise nature of which is unknown. For some proteins, it is closely related to coated pit determinants. The fact that many membrane proteins can reach the apical surface in the absence of this determinant suggests that signals for apical transport are widely distributed. PMID- 1909607 TI - Effect of ritanserin, specific 5HT-2 antagonist, on PRL secretion in normal subjects and in different hyperprolactinaemic conditions. AB - The availability of a new specific anti 5HT-2 compound, ritanserin (RTS), led us to further investigate the role of serotonin in controlling PRL secretion. The drug was administered to normoprolactinaemic subjects and to patients with differing hyperprolactinaemic conditions. While RTS failed to modify PRL levels in normoprolactinaemic subjects and in patients with PRL-secreting pituitary adenomas, a marked decrease in the hormone was obtained in patients with functional and puerperal hyperprolactinaemia. The lack of effect of RTS in PRL secreting pituitary adenomas suggests that the reported suppression of PRL by other antiserotoninergic drugs, such as metergoline, is probably due to their concomitant dopaminergic activity. PMID- 1909608 TI - Male pseudohermaphroditism due to Leydig cell agenesia and absence of testicular LH receptors. AB - OBJECTIVE: The aim of our study was to establish the definitive diagnosis in an adult patient with male pseudohermaphroditism in whom testicular feminization syndrome had been suspected at the age of 8, based on genetic, clinical and pathological studies. DESIGN: Hypothalamo-hypophysio-testicular function was assessed in vivo. Androgen mechanism of action and testicular gonadotrophin binding were studied in vitro. PATIENT: At the age of 33 the phenotype was almost completely feminine except for slight clitoral enlargement and posterior labial fusion. Internal genital duct derivatives were masculine except for a short vagina. Both testes were cryptorchid. MEASUREMENTS: LH and FSH were determined pre- and post-gonadectomy. Progesterone, 17-OH-progesterone, androstenedione, dehydroepiandrosterone testosterone (T) and oestradiol were determined basally in peripheral and spermatic blood post-hCG stimulation, and in peripheral blood after orchidectomy. Dihydrotestosterone (DHT) receptors and 5 alpha-reductase activity were determined in genital skin fibroblasts. Receptors for LH and FSH were determined in membrane preparations from both testes. RESULTS: LH was high (31 IU/l) and FSH (8 IU/ml) normal. T or steroid precursors were detected basally or after hCG stimulation in peripheral blood showing absence of testicular production. Spermatic venous blood steroid concentrations were consistent with slight T production, in accordance with testis histology which showed few Leydig like cells among fibroblasts in the interstitial space. DHT specific binding capacity and affinity and 5 alpha-reductase activity were normal in genital skin fibroblasts. Gonadotrophin binding studies in testicular membranes confirmed the absence of LH specific binding, whereas FSH binding was higher than normal when expressed per mg of protein (27.0 vs 9.4 +/- 0.6 fmol/mg protein in controls), and lower than normal in both testes since patient's testicular weights were abnormally low. CONCLUSIONS: The patient was considered to have an almost complete form of Leydig cell agenesia/hypoplasia in which absence of specific LH binding correlated with total absence of differentiated Leydig cells and insensitivity of undifferentiated interstitial cells to LH stimulation. PMID- 1909609 TI - Stimulation and suppression of intact parathyroid hormone (PTH1-84) in normal subjects and hyperparathyroid patients. AB - OBJECTIVE: Because of an overlap between serum PTH values in healthy controls and hyperparathyroid patients we sought to evaluate a short stimulation and suppression test for differentiating the two groups. SUBJECTS: Subjects were 34 patients with primary hyperparathyroidism (PHPT) and 25 healthy controls. DESIGN: After stimulation with intravenous EDTA (10 mg/kg body weight in 5 minutes) blood samples were obtained for up to 15 minutes. After an oral calcium dose of 1 g, blood samples were obtained at 1 and 2 hours. After an intravenous calcium dose (2.5 mg/kg body weight in 30 seconds), blood samples were obtained serially for 20 minutes. MEASUREMENT: Serum PTH(1-84) was measured by a double antibody technique. RESULTS: The intravenous EDTA test resulted in an average 2.6-fold increase of serum PTH(1-84) in hyperparathyroid patients, whereas it increased 10.5-fold in controls. A response was absent in three of 23 patients. There was an overlap in results between patients with mild hyperparathyroidism and controls. The oral calcium dose decreased serum PTH(1-84) in patients to 0.73 and in controls to 0.55 of the basal value, but six of 15 patients and two of 12 controls did not respond. The intravenous calcium test resulted in a drop of serum PTH(1-84) in hyperparathyroid patients to 0.51 and in control subjects to 0.40 of the basal value, and non-responders were not observed. There was a strong correlation between the responses to the EDTA and the calcium infusion tests in the patients (r = 0.97, P less than 0.01). Fasting serum calcium and serum PTH(1 84) showed a positive correlation in PHPT patients (r = 0.75, P less than 0.001) and a negative correlation in control subjects (r = -0.41, P less than 0.05). Based on these relationships, hyperparathyroid patients and controls could be completely separated. CONCLUSION: The wide range of responses to stimulation and suppression tests and the correlation between these responses in hyperparathyroid patients indicate various degrees of autonomy. As the response to these tests is less marked in patients than in controls and both groups still overlap, these tests are not useful for the diagnosis of primary hyperparathyroidism. PMID- 1909610 TI - Critically ill patients have high basal growth hormone levels with attenuated oscillatory activity associated with low levels of insulin-like growth factor-I. AB - OBJECTIVE: The aim was to study the relationship between growth hormone (GH) and insulin-like growth factor-I (IGF-I) in critically ill patients. DESIGN: Case control study of critically ill patients admitted to the intensive care unit was carried out. PATIENTS: Six critically ill patients (51-78 years) who required ventilation and parenteral nutrition and six age, weight, height, and sex-matched healthy adults were studied. MEASUREMENTS: The patients and controls were studied for two 24-hour periods; the patients before and after starting parenteral feeding, and the controls during a 36-hour fast and when taking meals equivalent in calories and protein to the patients' parenteral feed. Serum GH was measured at 20-minute intervals and analysed by a pulse detection algorithm (Pulsar) and Fourier transformation. IGF-I was measured at 0, 12, and 24 hours. RESULTS: Patients had low serum IGF-I levels compared with controls, whether fasted or fed, despite having mean GH levels similar to fasted controls. For fasted patients vs fasted controls the mean (+/- 1 SD) GH levels were 4.5 +/- 2.0 vs 4.0 +/- 2.4 mU/l respectively, and IGF-I levels at the end of the fast were 0.17 +/- 0.11 vs 0.78 +/- 0.29 U/ml (P = 0.003). Patients showed elevated baseline GH levels compared with controls when fasted and during parenteral feeding (patients vs controls fasted 3.1 +/- 1.9 vs 0.8 +/- 0.5 mU/l, P = 0.01; patients vs controls fed 4.2 +/- 4.5 vs 0.5 +/- 0.04 mU/l, P = 0.028). Fourier transformation confirmed oscillatory GH levels in the controls, fasted or fed, but this activity was attenuated in the patients. Parenteral feeding had no effect on the GH profiles or IGF-I levels of patients, but controls showed greater mean GH levels during their fast than when fed. CONCLUSIONS: We have demonstrated that critically ill patients have low IGF-I levels associated with augmented baseline GH levels which show reduced oscillatory activity. The results would be compatible with the hypothesis that there is an adaptive change in critically ill patients away from the indirect effects of GH (stimulation of IGF-I production and anabolism) and toward the direct effects (lipolysis and insulin antagonism) which increase the availability of energy substrates. The pattern of GH levels seen in our patients may be important in this adaptation. PMID- 1909611 TI - Control of immunoactive inhibin production by human granulosa cells. AB - OBJECTIVE: The aim was to determine the relation between stage of antral follicular development and granulosa cell production of immunoactive inhibin. DESIGN: Primary granulosa cell cultures in serum-free Medium 199 were incubated at 37 degrees C for 96 hours with a change of medium at 48 hours. Inhibin and steroid levels in culture medium were determined by radioimmunoassay. The inhibin assay was based on the N-terminal 1-26 amino acid sequence of the alpha-chain of porcine 32 kDa inhibin using pl alpha 1-26-GLY27-TYR28 as the immunogen, tracer and standard. PATIENTS: Granulosa cells were obtained from the ovaries of women with regular menstrual cycles undergoing hysterectomy with unilateral or bilateral oophorectomy to treat non-malignant gynaecological disease. RESULTS: Basal production of immunoactive inhibin by granulosa cells from presumptive preovulatory follicles (greater than 15 mm diameter) was 5-13 times higher than that by granulosa cells from immature (less than 10 mm diameter) or intermediately mature (10-15 mm diameter) follicles. Basal production of progesterone and oestradiol followed a qualitatively similar pattern, establishing a positive relation between functional granulosa cell maturity and inhibin production. Treatment of granulosa cell cultures from immature follicles with follicle-stimulating hormone (FSH), but not luteinizing hormone (LH), increased inhibin production, time and dose dependently. FSH, but not LH, also brought about similar increases in steroid hormone synthesis by granulosa cells from immature follicles. The stimulatory effect of FSH on granulosa cell inhibin production was augmented at least twofold by the presence of testosterone or 5 alpha-dihydrotestosterone (1.0 mumol/l) but was unaffected by oestradiol. Granulosa cells from intermediately mature follicles undertook variable degrees of both FSH and LH-responsive inhibin production which generally corresponded with gonadotrophin-responsive steroid production. Granulosa cells from presumptive preovulatory follicles showed inconsistent inhibin responses to FSH. However, LH caused marked (at least twofold) increases in inhibin production, paralleling LH-responsive steroid production. CONCLUSION: These results show that for human beings, granulosa cell capacity to produce immunoactive inhibin in vitro increases with follicular maturity. FSH, but not LH, stimulates inhibin production by immature granulosa cells and this response to FSH is subject to modulation by androgen. During preovulatory follicular development, production of inhibin, like steroids, becomes increasingly responsive to LH. Such a development related pattern of granulosa cell inhibin production helps explain how, post ovulation, the corpus luteum is able to secrete inhibin as well as steroids. It is also compatible with the concept that locally produced inhibin could participate in the paracrine control of follicular development during the human menstrual cycle. PMID- 1909612 TI - Post partum renal failure in systemic lupus erythematosus associated with circulating lupus anticoagulant and anticardiolipin antibody. PMID- 1909613 TI - Cefpirome, alone and in combination with gentamicin for enterococcal pyelonephritis in the rodent model. AB - The in vitro and in vivo activity of cefpirome (CF) against Enterococcus faecalis GK strain was examined. The ratio of minimal inhibitory to bactericidal concentration (MIC/MBC) values in microgram/ml were (a) ampicillin 0.8/1.5; (b) gentamicin 2/25; (c) vancomycin, 0.8/50; and (d) CF, 8/32. A time-kill study using 10(7) organisms per milliliter showed a drop of 3 logs10 at 4 hr in the tube containing cefpirome (10 micrograms/ml) as well as the tube containing cefpirome (5 micrograms/ml) plus gentamicin (GM) (2 micrograms/ml), as compared to the control and the tube containing GM at 4 micrograms/ml. At 8 and 24 hr, however, regrowth to control levels occurred. Of this enterococcal strain consisting of 10(8) organisms, 1 ml was then injected intravenously by tail vein into 150 male Wistar rats weighing 120 g each. Eleven days after injection, 10 rats were killed and the remaining ones were randomized into four treatment groups: (a) untreated control; (b) BM, 0.9 mg; (c) CF, 10 mg; and (d) CF + GM. The rats received the injections intramuscularly twice daily. At least 10 rats from each group were killed for quantitative kidney cultures at 1, 2, and 4 weeks after start of therapy. At the end of 4 weeks of therapy, the results were significantly better in the combination group compared to the other three groups. PMID- 1909614 TI - Susceptibility testing of Listeria monocytogenes. A reassessment of bactericidal activity as a predictor for clinical outcome. AB - In vitro susceptibility testing of Listeria monocytogenes most often reveals both ampicillin and penicillin as inhibitory as opposed to bactericidal with activity comparable to chloramphenicol and tetracycline. Yet, the former two penicillins are more effective for Listeria meningitis than are the latter agents. Accordingly, we reassessed the bactericidal activity of agents used in listeriosis in order to determine in vitro methodology that would be more predictive of clinical outcome. We found that bactericidal activity for greater than 48 hr by either minimum inhibitory-minimum bactericidal concentration (MIC MBC) testing or time-kill kinetic studies was the best predictor of clinical efficacy. This correlation may be due to Listeria being a slow-growing microorganism. In addition to ampicillin and penicillin, we found trimethoprim sulfamethoxazole, vancomycin, and imipenem to exhibit bactericidal activity for 48 hr. For the first two agents, this is in agreement with the results of clinical experience. PMID- 1909615 TI - In vitro antimicrobial activity of sparfloxacin (AT-4140, CI-978, PD 131501) compared with numerous other quinolone compounds. AB - Sparfloxacin (AT-4140, CI-978, PD 131501) was tested against over 800 recent bacteremic strains and compared with ciprofloxacin and six other fluoroquinolones. The 90% minimum inhibitory concentration (MIC90) ranges for the Enterobacteriaceae species were (a) sparfloxacin, 0.03-1 microgram/ml and (b) ciprofloxacin, 0.015-0.25 microgram/ml. Moraxella catarrhalis, Haemophilus influenzae, and Neisseria gonorrhoeae were very susceptible to sparfloxacin (MIC90s, 0.004- less than or equal to 0.03 microgram/ml) and the other comparison drugs. Staphylococcus aureas and other staphylococci were generally susceptible to the tested fluoroquinolones but very susceptible to sparfloxacin and WIN 57273. All beta-hemolytic streptococci, enterococci, and pneumococci had sparfloxacin MICs of less than or equal to 1 microgram/ml. Sparfloxacin was quite active against anaerobic bacteria including Bacteroides fragilis gr. and Gram positive strains (MIC90s, less than or equal to 2 micrograms/ml). The most resistant enteric bacilli were among Serratia marcescens and the Proteae, especially the Providencia spp. (two- to eightfold higher MICs). Pseudomonas aeruginosa strains were also susceptible to sparfloxacin (MIC90, 2 micrograms/ml). Magnesium ions, CO2 incubation, and low pH had some adverse effect on sparfloxacin MICs, and resistance development was documented among current clinical isolates of staphylococci, pseudomonas, and some enteric species. PMID- 1909616 TI - Pathogenesis of corneal epithelial defects: role of plasminogen activator. AB - Previous studies have suggested that the plasminogen activator (PA)/plasmin system has important roles in the pathogenesis of epithelial defects and stromal ulceration. The current studies were performed to localize PA species and identify them as tissue-type PA (tPA) or urokinase-like PA (uPA) as the two have distinct regulatory properties potentially related to the mechanisms of defect formation and ulceration. To determine the locations and types of PA species, antibodies to tPA or to uPA or the drug amiloride (a drug that inhibits uPA but not tPA) were incorporated into fibrin/fibronectin (Fn) clots overlying frozen sections to block regional fibrinolysis. Normal rabbit eyes showed tPA activity in association with corneal epithelium, corneal endothelium, and ciliary body/iris. After epithelial scrape or alkali burn, corneal tPA activity was detected initially in the defect zone colinear with fibrin/Fn and was symmetrical to resurfacing epithelium. The observation that initial fibrinolysis occurs in the defect zone, known to contain fibrin/Fn, suggests that tPA from blood (limbal vascular endothelium) and/or from corneal epithelium has become bound to (and activated on) the fibrin/Fn. PA activity was also associated with the leading edges of migrating epithelium post-scrape and post-burn and was not inhibited by antibodies to either tPA or uPA but was inhibited by amiloride. After complete closure of the primary defect post-scrape, only tPA appeared to be associated with the epithelium in that all PA activity was inhibited by antibodies to tPA. The observation that leading edge activity post-burn, in correlation with the formation of secondary defects, continues to be inhibitable by amiloride but not by antibodies to tPA suggests that uPA remains abnormally on the leading edge, and that sustained uPA activity in that location results in inappropriate degradation of subepithelial fibrin/Fn to result in a defect. Successful regulation of uPA activity at the leading edge of corneal epithelium post-burn would be expected to be useful therapeutically in the healing of epithelial defects and the prevention of stromal ulceration. PMID- 1909617 TI - Clinical, laboratory, roentgenographic, and electrocardiographic findings in patients with acute pulmonary embolism and no pre-existing cardiac or pulmonary disease. AB - The history, physical examination, chest radiograph, electrocardiogram and blood gases were evaluated in patients with suspected acute pulmonary embolism (PE) and no history or evidence of pre-existing cardiac or pulmonary disease. The investigation focused upon patients with no previous cardiac or pulmonary disease in order to evaluate the clinical characteristics that were due only to PE. Acute PE was present in 117 patients and PE was excluded in 248 patients. Among the patients with PE, dyspnea or tachypnea (greater than or equal to 20/min) was present in 105 of 117 (90 percent). Dyspnea, hemoptysis, or pleuritic pain was present in 107 of 117 (91 percent). The partial pressure of oxygen in arterial blood on room air was less than 80 mm Hg in 65 of 88 (74 percent). The alveolar arterial oxygen gradient was greater than 20 mm Hg in 76 of 88 (86 percent). The chest radiograph was abnormal in 98 of 117 (84 percent). Atelectasis and/or pulmonary parenchymal abnormalities were most common, 79 of 117 (68 percent). Nonspecific ST segment or T wave change was the most common electrocardiographic abnormality, in 44 of 89 (49 percent). Dyspnea, tachypnea, or signs of deep venous thrombosis was present in 107 of 117 (91 percent). Dyspnea or tachypnea or pleuritic pain was present in 113 of 117 (97 percent). Dyspnea or tachypnea or pleuritic pain was present in 113 of 117 (97 percent). Dyspnea or tachypnea or pleuritic pain or atelectasis or a parenchymal abnormality on the chest radiograph was present in 115 of 117 (98 percent). In conclusion, among the patients with pulmonary embolism that were identified, only a small percentage did not have these important manifestations or combinations of manifestations. Clinical evaluation, though nonspecific, is of considerable value in the selection of patients in whom there is a need for further diagnostic studies. PMID- 1909618 TI - The value of flexible bronchoscopy in childhood pulmonary tuberculosis. AB - The value of 121 flexible bronchoscopy (FB) procedures was evaluated in 54 children, aged three months to 14 years, suspected of having pulmonary tuberculosis. Specimens from FB were culture-positive for Mycobacterium tuberculosis in seven of the 13 bacteriologically confirmed cases. Bronchial abnormalities consistent with the diagnosis were found in 31 of 54 cases. Separate or coexistent findings at initial FB included airway compression (20 cases), granulation tissue (ten cases), and obstructive caseum (four cases). Chest roentgenograms underestimated bronchial involvement in 14 children. Further FB monitoring documented disease evolution. The FB was important in the management of patients, as it (1) guided the use of prednisone therapy, especially in the children with a chest roentgenogram not suggestive of bronchial involvement; (2) indicated a need for resection of granulation tissue by rigid bronchoscopy (three cases); and (3) guided the surgical decision (two children with persistent bronchial obstruction). Thus, FB is a safe and valuable procedure in the management of childhood pulmonary tuberculosis. PMID- 1909619 TI - The control of breathing during weaning from mechanical ventilation. AB - Using the recruitment threshold technique, we measured the CO2 responsiveness of the unloaded respiratory pump in 14 mechanically ventilated patients prior to weaning. The CO2 recruitment threshold (CO2RT) was compared with the arterial CO2 tension during unassisted breathing (CO2SB) and with the PaCO2 during mechanical ventilation (CO2MV) at machine settings determined by the primary physician. Based on these comparisons, we tested the hypotheses that (1) patients without weaning-induced respiratory distress (group 1) maintain CO2SB near CO2RT, (2) patients with weaning-induced respiratory distress (group 2) retain CO2SB above CO2RT, thereby manifesting incomplete load compensation, and (3) CO2MV is ventilator setting dependent and provides insufficient information about the ventilatory requirement during weaning. Respiratory distress was prospectively defined as sustained tachypnea (rate greater than or equal to 30) or intense dyspnea (Borg scale rating) and limited weaning in nine of 14 patients. The average CO2RT was 40 mm Hg in both groups. All patients in group 1 maintained CO2SB near CO2RT (p greater than 0.1). Seven of nine patients in group 2 retained CO2 by greater than or equal to 3 mm Hg above CO2RT (p less than 0.01). There was no significant difference between CO2MV and CO2SB in either group. We conclude that CO2RT provides a better reference of the adequacy of ventilatory load compensation during weather than CO2MV. PMID- 1909620 TI - A case of chronic mountain sickness diagnosed by routine pulmonary function tests. AB - In summary, this is a patient who presented with respiratory acidosis and cor pulmonale. The major diagnostic challenge was in differentiating primary cardiopulmonary disease from a central abnormality of ventilatory drive. The arterial blood gases showed a normal A-a gradient suggesting hypoventilation as the etiology of his hypoxemia. Pulmonary function testing showed air trapping, but a relatively normal FEV1/FVC and airways resistance. The literature suggests that most altitude natives have depressed hypoxemic and hypercapnic drives with a distinct subset demonstrating a profoundly depressed drive to ventilation. This latter group has been labeled as having chronic mountain sickness or Monge's disease. As one might expect, ventilatory control during sleep is also abnormal in these patients with CMS. Our patient indeed showed typical frequent severe desaturations with hypopnea. The diagnosis of CMS in our patient was made with routine arterial blood gases and standard pulmonary function tests. Additional tests of ventilatory responsiveness to oxygen and carbon dioxide could have been performed, but are not necessary to make the diagnosis. PMID- 1909621 TI - Very severe self-poisoning lithium carbonate intoxication causing a myocardial infarction. AB - A case of severe lithium carbonate self-poisoning is described, presenting with a very high serum lithium level (14.6 mmol/L) on admission. Lengthy and repeated hemodialyses were required to lower lithemia to nontoxic ranges. As is usually reported, our patient had prolonged neurologic manifestations (coma, hyperreflexia, fluctuating focal signs) and developed hypotension, cardiovascular collapse, nephrogenic diabetes insipidus, and diarrhea. Other less common features were the occurrence of acute myocardial infarction without coronary artery lesions and thrombocytopenia. The possible pathogenic mechanisms are discussed. Hemodialysis and supportive intensive care treatment are commented upon. The final outcome was favorable, and the patient recovered completely. PMID- 1909622 TI - Effect of fleroxacin and ciprofloxacin on the formation of human mature colonies of healthy donor versus transplanted hemopoietic progenitor cells. AB - The effect of fleroxacin and ciprofloxacin on hemopoietic progenitor cells was tested in vitro. Cryopreserved bone marrow samples from 5 patients with acute myeloid leukemia who underwent bone marrow transplantation as well as samples from the respective donors were investigated in parallel. Regarding burst and/or colony formation by erythroid, neutrophil and macrophage precursors, no significant differences were detected with donor and transplanted bone marrows between control cultures and cultures containing 100 mg/l fleroxacin, while 100 mg/l ciprofloxacin inhibited cell proliferation completely. At 50 and 10 mg/l ciprofloxacin had a 50% and no inhibitory effect, respectively. PMID- 1909623 TI - Effect of subchronic aflatoxin exposure on growth and progression of Ehrlich's ascites tumor in mice. AB - The present investigation was undertaken to assess whether aflatoxin B1 (AFB1) has any modulatory effect on the growth and progression of Ehrlich's ascites tumor (EAT) in mice or not. Male Swiss albino mice were treated with 0, 70, 350 and 700 micrograms AFB1/kg body weight in 0.2 ml corn oil on alternate days, orally, for two weeks. Treated animals were challenged with 1 x 10(6) cells of Ehrlich's ascites tumor. Animals were monitored for the appearance of palpable tumor, body weight gain as a measure of tumor burden, mortality profile and tumor cell population. Some parameters of cell mediated immunity (CMI), humoral immunity and non-specific immunity were also studied in aflatoxin treated animals in order to find out the mechanism of action of AFB1 on host immunity. It was observed that AFB1 treatment resulted in an early appearance of tumor, enhanced mortality, appreciable increase in body weight gain and EAT cell population following tumor challenge, in comparison with the control animals. Aflatoxin treatment caused suppression of CMI including an impairment of macrophage function, while humoral immunity was not much affected. It may be concluded that impaired CMI and macrophage function might be contributing to the increased growth of EAT in the AFB1 treated animals. Our findings may be relevant in that when a host is exposed to aflatoxins concomitantly with other carcinogens and cancer causing situations. PMID- 1909624 TI - Structure of the beta-glucosidase gene bglA of Clostridium thermocellum. Sequence analysis reveals a superfamily of cellulases and beta-glycosidases including human lactase/phlorizin hydrolase. AB - The nucleotide sequence of the Clostridium thermocellum gene bglA, coding for the thermostable beta-glucosidase A, has been determined. The coding region of 1344 bp was identified by comparison with the N-terminal amino acid squence of recombinant beta-glucosidase A purified from Escherichia coli. The deduced amino acid sequence corresponds to a protein of 51,482 Da. The coding region is flanked by putative promoter and transcription terminator sequences. The protein is unrelated to beta-glucosidase B of C. thermocellum, but has a high level of similarity with other bacterial beta-glucosidases and phospho-beta-glucosidases. Similarity is also observed with the beta-galactosidase of the archaebacterium Sulfolobus solfataricus. Unexpectedly, it was found that human lactase-phlorizin hydrolase contains three copies of a sequence closely related to C. thermocellum beta-glucosidase A (up to 40% sequence identity). These diverse beta-glucosidases can therefore be grouped into an enzyme family (BGA) of common structural design. Sequence comparison by hydrophobic cluster analysis revealed that all BGA enzymes share a well conserved region which is homologous to the catalytic domain of the widely distributed cellulase family A. A distinctive feature of this domain is the sequence motif His-Asn-Glu-Pro in which the catalytic residues His and Glu are separated by 35-55 amino acid residues. The cellulase family A and the beta glucosidase family BGA might thus be considered as members of a protein super family comprising beta-glucanases and beta-glycosidases from all three primary kingdoms of living organisms. PMID- 1909625 TI - Purification and properties of a novel type of exo-1,4-beta-glucanase (avicelase II) from the cellulolytic thermophile Clostridium stercorarium. AB - Avicelase II was purified to homogeneity from culture supernatants of Clostridium stercorarium. A complete separation from the major cellulolytic enzyme activity (avicelase I) was achieved by FPLC gel filtration on Superose 12 due to selective retardation of avicelase II. The enzyme has an apparent molecular mass of 87 kDa and a pI of 3.9. Determination of the N-terminal amino acid indicates that avicelase II is not a proteolytically processed product of avicelase I. Maximal activity of avicelase II is observed between pH 5 and 6. In the presence of Ca2+, the enzyme is highly thermostable, exhibiting a temperature optimum around 75 degrees C. Hydrolysis of avicel occurs at a linear rate for three days at 70 degrees C. Avicelase II is active towards unsubstituted celluloses, cellotetraose and larger cellodextrins. It lacks activity towards carboxymethylcellulose and barley beta-glucan. Unlike other bacterial exoglucanases, avicelase II does not hydrolyze aryl-beta-D-cellobiosides. Avicel is degraded to cellobiose and cellotriose at a molar ratio of approximately 4:1. With acid-swollen avicel as substrate, cellotetraose is also formed as an intermediary product, which is further cleaved to cellobiose. The degradation patterns of reduced cellodextrins differ from that expected for a cellobiohydrolase attacking the non-reducing ends of chains; cellopentaitol is degraded to cellobiitol and cellotriose, while cellohexaitol is initially cleaved into cellobiitol and cellotetraose. These findings, taken together, indicate that avicelase II represents a novel type of exoglucanase (cellodextrinohydrolase), which, depending on the accessibility of the substrate, releases cellotetraose, cellotriose, or cellobiose from the non reducing end of the cellulose chains. PMID- 1909627 TI - Uncoupled changes in the expression of the jun family members during myeloid cell differentiation. AB - The differentiation into macrophages of the U937 and HL60 human cell lines induced by 4 beta-phorbol 12-myristate 13-acetate (PMA) was accompanied by induction of the expression of the proto-oncogenes c-jun, jun B and jun D. However, expression of the three jun genes was regulated differently during induction of cell differentiation in both U937 and HL60 cells, with the three jun family members being expressed distinctly at different stages of cell differentiation. Whereas jun B transcription was strongly stimulated following treatment with PMA for 30 min, jun D mRNA levels were only increased 6 h after PMA treatment and the content of c-jun mRNA was elevated maximally only 24 h after PMA treatment. The rapid induction of the jun B mRNA level suggests a putative role for this proto-oncogene in the early triggering step of U937 and HL60 cell differentiation induced by PMA. Interestingly, a weak induction of jun B and jun D mRNA levels, but no induction of the c-jun mRNA level, was detected during Me2SO-induced granulocytic HL60 differentiation. These data suggest a different role for each jun proto-oncogene in regulating gene activity and that different transcriptional complexes involving distinct jun proto-oncogenes can be formed during macrophage and granulocytic differentiation. PMID- 1909626 TI - Isolation and characterization of hyodeoxycholic-acid: UDP glucuronosyltransferase from human liver. AB - The enzyme hyodeoxycholic-acid: UDP-glucuronosyltransferase was purified about 230-fold from a solubilized human liver microsomal preparation utilizing anion exchange chromatography, ampholyte-displacement chromatography and UDP hexanolamine--Sepharose affinity chromatography. The homogeneity of the final enzyme preparation was judged by two criteria: the appearance of a single band of Mr 52000 in SDS/PAGE; the elution of a single peak in reversed-phase FPLC. The isolated enzyme catalyzed the glucuronidation of the 6 alpha-hydroxy bile acids hyodeoxycholic and hyocholic acids, and of the steroid hormone estriol, with a ratio of relative reaction rates of 13:1:2.7. UDP-glucuronosyltransferase activities toward the 3 alpha-hydroxy bile acid lithocholic acid, androsterone, testosterone, bilirubin and p-nitrophenol were not detectable in the pure enzyme preparation and were shown to be separated from enzyme activity toward hyodeoxycholic acid during ampholyte-displacement chromatography and/or UDP hexanolamine--Sepharose affinity chromatography. Two-substrate kinetic analysis of hyodeoxycholic-acid-conjugating activity gave a sequential mechanism with apparent Km values of 12 microM and 4 microM for hyodeoxycholic acid and UDP glucuronic acid, respectively. Phospholipids were required for reconstitution of maximal activity toward hyodeoxycholic acid. Phosphatidylcholine was the most effective activator of enzyme activity. PMID- 1909628 TI - Comparison of the fibrinolytic response to desmopressin acetate (DDAVP) infusion versus venous occlusion in patients with coronary artery disease. AB - A 20-min venous occlusion and a desmopressin acetate (DDAVP, 0.4 microgram.Kg-1, 15 min) infusion test have been compared to evaluate fibrinolytic capacity in proven coronary artery disease. Basal values of plasma tissue plasminogen activator (t-PA) activity and antigen and of t-PA inhibitor (PAI) were normally distributed in this patient group. However, after both stimuli, highly significant (P less than 0.005) increases of t-PA antigen and activity have been observed. Renormalization of t-PA levels after DDAVP infusion occurred more rapidly for antigen (120 min) than for activity concentrations (greater than 240 min). A DDAVP infusion test seems more appropriate for evaluation of the fibrinolytic capacity as the induced decrease in PAI level was significant (P less than 0.005) and lasted for at least 240 min, while it was not significant for the venous occlusion test. PMID- 1909629 TI - Biliary lipid secretion in man. PMID- 1909630 TI - Chloride-depletion metabolic alkalosis induces ECF volume depletion via internal fluid shifts in nephrectomized dogs. AB - We recently reported that chloride-depletion metabolic alkalosis (CDMA) results in renal losses of Na, K, and water. In these studies we investigated whether CDMA (induced using a new model that avoids external changes in Na and water balance) was also associated with internal Na and water shifts out of the ECF. CDMA was induced using haemofiltration in functionally nephrectomized dogs. Plasma ultrafiltrate was substituted quantitatively with a solution duplicating each dog's plasma electrolyte composition in control animals, and with a solution containing HCO3 as the sole anion in CDMA animals. ECF volume was estimated as the space of distribution of [3H]-mannitol. Plasma composition and [3H]-mannitol distribution space were unchanged in control dogs. In CDMA dogs metabolic alkalosis developed; despite the absence of external changes in Na and water balance, the space of distribution of [3H]-mannitol decreased by 335 +/- 46 ml (equivalent to 8% of baseline ECF volume), calculated chloride space fell by 304 +/- 50 ml, and haematocrit increased from 45.6 to 48.5 vol%. We conclude that CDMA causes an internal shift of fluid out of the ECF. The resulting ECF volume contraction appears to be an inherent feature of CDMA. PMID- 1909631 TI - High blood pressure and insulin resistance: influence of ethnic background. AB - Hyperinsulinaemia links non-insulin dependent diabetes (NIDDM), obesity, and hypertension, each an insulin-resistant state in its own right. Insulin resistance predicts the occurrence of NIDDM, and plays a major role in its pathogenesis. We tested the hypothesis that hyperinsulinaemia may also predict hypertension in a sample (n = 2905) of the mixed population of San Antonio, in which hyperinsulinaemia and NIDDM are more prevalent among Mexican-Americans than non-Hispanic whites. Whilst in the whole sample the hypertensives had significantly (P less than 0.001) higher plasma insulin concentrations than the normotensives, high blood pressure was significantly (P less than 0.01) more frequent among non-Hispanic whites than Mexican-Americans regardless of diabetes status. After adjusting for factors (age, sex, body mass, and body fat distribution) known to affect insulin levels, a direct relationship between post glucose plasma insulin concentrations and prevalence of hypertension was still present in both ethnic groups. In Mexican-Americans, however, the standardized prevalence of hypertension was significantly (P less than 0.001) lower at any given insulin concentration. Post-glucose plasma glucose levels also were directly related to hypertension prevalence in both groups; again, the regression line was shifted downward and, furthermore, less steep (P less than 0.02) in Mexican-Americans, suggesting relative protection against the negative effect of hyperglycaemia on blood pressure. Dyslipidaemia (higher total cholesterol and triglyceride, and lower HDL-cholesterol concentrations) was strongly associated with hyperinsulinaemia and blood pressure in both ethnic groups. After adjusting for plasma insulin, only hypertriglyceridaemia was associated with high blood pressure, with no inter-ethnic difference.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1909632 TI - Complement activation and depletion during LDL-apheresis by heparin-induced extracorporeal LDL-precipitation (HELP). AB - The heparin-induced extracorporeal elimination of low density lipoproteins (LDL) is a well-established clinical procedure to markedly reduce cholesterol levels. The biocompatibility of this artificial filter system (HELP) was investigated by quantitation of representative complement proteins within the extracorporeal circuit using established ELISA procedures, based on monoclonal antibodies recognizing exclusively either native (C6, C7) or activated proteins (act.C3, C5a, TCC). HELP was found to be a self-limiting extracorporeal system with respect to complement activation, since act.C3 and TCC, generated mainly at the plasma filter, were partially adsorbed to the following HELP specific filters to concentrations which were lower than those obtained before the plasma filter. C5a, which increased 14.5-fold at the plasma filter was not eliminated by the following filters; however, elevated levels were not found in the patients at the end of apheresis and no leucocytopenia was observed. PMID- 1909633 TI - Identification of patients at high risk for colorectal carcinoma from biopsy studies of the apparently normal colorectal mucosa. A multivariate analysis. AB - A number of phenotypic abnormalities of the colorectal mucosa which appears normal have been described to be biomarkers of cancer development. To improve their sensitivity and specificity, we simultaneously determined 10 morphological and histochemical parameters in biopsies from the colonoscopically normal mucosa of the descending colon, sigmoid, and rectum. The results were analysed by multivariate statistical methods. We tested the discriminating power of proliferative, morphometric, enzyme and mucin histochemical parameters from 80 patients either at average risk (controls), with an increased risk for colorectal carcinoma (high-risk), or with a manifest carcinoma. The following parameters were investigated: number of mitotic figures per crypt, crypt length, apical, medial and basal crypt diameter, crypt surface, activity of succinate dehydrogenase (EC 1.3.99.1), activity of acid beta-galactosidase (EC 3.2.1.23), sulpho- and sialomucin contents. Univariate statistical analyses revealed that crypt length, crypt diameter and crypt surface were significantly increased in the high-risk group, the carcinoma carriers having intermediate values between average-risk and high-risk patients. In a two-group discriminant analysis, high risk or carcinoma patients could be separated from average-risk patients with a sensitivity of 92.9% and a specificity of 100%. When the analysis was repeated for three groups (carcinoma carriers separated from high-risk patients), sensitivity and specificity were 100% for each group. We conclude that identification of patients at risk for colorectal carcinoma is possible from the normal-appearing left colonic and rectal mucosa by morphometric and cytochemical analysis of biopsies. PMID- 1909634 TI - Involvement of heparin cofactor II in chymotrypsin neutralization and in the pancreatic proteinase-antiproteinase interaction during acute pancreatitis in man. AB - Heparin cofactor II is a proteinase inhibitor which inhibits both chymotrypsin and thrombin, and displays great similarities with antithrombin III, the main inhibitor of thrombin in human plasma. Since acute pancreatitis is known to be associated with modification of the proteinase-antiproteinase equilibrium, we studied heparin cofactor II and antithrombin III as well as other biochemical and haematological parameters in 10 patients experiencing attacks of acute pancreatitis. Heparin cofactor II activity decreased during the first week of illness, while its antigen concentration remained subnormal. This discrepancy between antigen concentration and activity which persisted during the first week of illness was due both to complex formation of heparin cofactor II with its target proteinases and to partial proteolysis of the inhibitor. Heparin cofactor II was shown to form a complex with chymotrypsin in the plasma of such patients. Antithrombin III levels remained unchanged throughout the study, with no discrepancy between its activity and antigen concentration. No modification of haemostasis was shown either, except for a rise in the fibrinogen level during the first days of illness. It is concluded that, unlike antithrombin III, heparin cofactor II is involved in the proteinase-inhibitor equilibrium in patients with acute pancreatitis, and that heparin cofactor II might react as an inhibitor of pancreatic proteinases rather than an inhibitor of thrombin. PMID- 1909635 TI - Evaluation of urinary hydroxypyridinium crosslink measurements as resorption markers in metabolic bone diseases. AB - Analyses of the urinary concentration relative to creatinine of the collagen crosslinks, pyridinoline (Pyd) and deoxy-pyridinoline (Dpd) were made in 47 patients with metabolic bone diseases to assess the validity of these assays as indicators of bone resorption. The mean values for patients with Paget's disease of bone, primary hyperparathyroidism and osteomalacia were significantly higher (P less than 0.001) than those for age-matched healthy individuals. During treatment of Paget's disease with bisphosphonates, there was a steady decline in the urinary concentration of the crosslinks to the normal range; this change occurred earlier than for serum alkaline phosphatase. There were significant correlations (P less than 0.01) between the concentrations of both crosslinks and the corresponding values for hydroxyproline. At lower crosslink concentrations, however, these relationships were less marked due to large variations in hydroxyproline values. The results show that measurements of urinary Pyd and Dpd provide clinically applicable indices of bone resorption that are more specific than other markers. PMID- 1909636 TI - Serum hyaluronate and type III procollagen aminoterminal propeptide concentration in chronic liver disease. Relationship to cirrhosis and disease activity. AB - To analyse the relationship between the presence of liver cirrhosis and hepatic inflammation and the serum concentrations of the aminoterminal propeptide of procollagen type III (P-III-NP) and of hyaluronic acid (HA) in chronic liver disease, we measured P-III-NP and HA concentrations in paired serum samples from 133 patients with various chronic liver diseases, from 22 patients with acute hepatitis and from 50 healthy age-matched controls. In 24 (of the 133) patients with autoimmune chronic liver disease, follow-up determination was performed during therapeutic treatment with immunosuppressive drugs. Compared with controls P-III-NP concentrations (medians) were significantly elevated in 65% of patients with chronic active hepatitis (P = 0.00097) and in 79% of patients with active liver cirrhosis (P = 0.0126) but not in patients with chronic persistent hepatitis (P = 0.06). Serum concentrations (medians) of HA were increased (P = 0.0058) in 32% of patients with chronic active hepatitis and in 91% of patients with active cirrhosis (P less than 6 x 10(-7)). The difference of HA serum concentrations but not that of P-III-NP serum concentrations in patients with chronic active hepatitis and in patients with active cirrhosis was statistically significant. HA and P-III-NP serum concentrations were significantly elevated in 22 patients with acute hepatitis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1909637 TI - Gemfibrozil in familial combined hyperlipidaemia: effect of added low-dose cholestyramine on plasma and biliary lipids. AB - Gemfibrozil is frequently used for lipid-lowering in familial combined hyperlipidaemia (FCHL) and in other forms of combined hyperlipidaemia. This therapy increases biliary cholesterol saturation, enhancing the risk for gallstone formation. Furthermore, in hypertriglyceridaemia, LDL cholesterol levels often tend to rise. We have explored the possibility that addition of a low dose of cholestyramine to gemfibrozil therapy obliterates these phenomena. Eighteen gallstone-free patients with definite (n = 5) or probable (n = 10) FCHL, or combined hyperlipoproteinaemia (n = 3) were randomized to a 6 week treatment with gemfibrozil, 600 mg b.i.d., or gemfibrozil 600 mg b.i.d. plus 4 g cholestyramine o.d. After 6 weeks the patients were crossed over to the alternative treatment. Plasma lipoproteins and biliary lipids were determined at baseline and at the end of each period. Institution of gemfibrozil treatment resulted in a decrease in plasma cholesterol by 15% (P less than 0.05) and in plasma triglycerides by 47% (P less than 0.05); HDL cholesterol increased by 18% (P less than 0.05). Addition of cholestyramine further decreased plasma and LDL total cholesterol by 9% (P less than 0.05). Total triglycerides and HDL cholesterol did not change. Gemfibrozil treatment was associated with a rise in the relative biliary concentration of cholesterol from 5.6 +/- 0.4 to 6.9 +/- 0.5 molar percent (P less than 0.01), and a parallel decrease in the relative concentration of bile acids, resulting in an increased cholesterol saturation of the bile, from 77 +/- 5 to 90 +/- 6% (P less than 0.05). This change was not observed during the combined therapy (mean cholesterol saturation, 82 +/- 4%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1909639 TI - Arterial wall hypoxia following thrombosis of the vasa vasorum is an initial lesion in atherosclerosis. AB - Pressure on the outside of arteries can cause physical and biochemical changes in the vessel wall of rabbits which are characteristic of atherosclerosis. It is hypothesized that occlusion of the vasa vasorum causes ischaemia of the arterial media which results in smooth muscle cell proliferation and cellular accumulation of cholesteryl esters. Hypoxia increases mRNA for platelet-derived growth factor in arterial wall cells and increases the activity of acyl CoA:cholesterol acyltransferase (ACAT). Such a mechanism may explain many of the anatomical, actuarial and environmental risk factors for atherosclerosis. Hypoperfusion may follow thrombosis of the vasa vasorum. PMID- 1909638 TI - Dynamics of creatine kinase shuttle enzymes in the human heart. AB - Myocardial cytoplasmic creatine kinase subunits M and B, mitochondrial CK (CKMIT), and citrate synthase (CS) were determined in 10 locations of the normal human heart (n = 8) and in papillary muscles of patients operated on for mitral regurgitation (n = 6). Compared to atrial biopsies, septal and left ventricular biopsies showed higher activities for CS (P less than 0.0001), total CK (P less than 0.05) and CKMIT (P less than 0.0001). CKM was evenly distributed. CKB activity in the right septum and left ventricular locations were 0.5-1% of total CK and 4-5 times lower than those of the atria and the right ventricular free wall. Activities of CS, CKB and CKMIT in right septal biopsies did not differ from those in left ventricular locations. The activities of CS, total CK, and CKM in papillary muscle from patients operated on for mitral regurgitation did not differ from that of healthy papillary muscle. CKMIT was about 40% lower (P less than 0.02), whereas CKB was 15-20 times higher (P less than 0.0001) than in the healthy heart. In conclusion, adaptations within the creatine kinase system occur in the human heart in health and disease. Small amounts of CKB in the normal left ventricle, as opposed to the right ventricular free wall, might be related to differences in myocardial perfusion during the cardiac cycle. In disease, a decreased CKMIT and dramatically increased CKB may indicate a stressed intracellular energy transfer. CK enzyme activities in right septal biopsy specimens may be used as an indication of metabolic stress on the myocardium of the left ventricle.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1909640 TI - A quantitative assay of peptide-dependent class I assembly. AB - We have developed a quantitative assay for the measurement of class I assembly induced by peptide. We have applied this assay to H-2Db, Kb and HLA-A2.1 with a panel of 49 overlapping peptides derived from HIV-1 gag protein. We find that the effects of peptide on assembly form a continuous distribution. By defining positives as those that increase the concentration of folded heavy chains more than three standard deviations from the control we show that 7/48 bind A2.1, 11/49 bind Db and 7/47 bind Kb. The assembly assay contrasts with solid-phase assays in being more discriminating (fewer peptides binding any given class I molecule), and showing less overlap in the patterns of peptides bound by the three class I molecules. PMID- 1909641 TI - Immunoregulation of mercuric chloride-induced autoimmunity in Brown Norway rats: a role for CD8+ T cells revealed by in vivo depletion studies. AB - Mercuric chloride (HgCl2) induces the production of autoantibodies to glomerular basement membrane (GBM) in the Brown Norway (BN) rat. The autoimmune response is self-limiting and thereafter the animals are resistant to rechallenge with HgCl2. Resistance can be transferred to naive animals by spleen cells from HgCl2-treated rats. A similar state of resistance can be induced with a low dose of HgCl2, insufficient in itself to induce autoimmunity. We have examined the role of CD8+ T cells in the immunoregulation of this experimental model by depleting this subset in vivo. We have also used inhibition studies in a solid-phase radioimmunoassay in an attempt to demonstrate any effect of anti-idiotypic antibodies in the spontaneous resolution of the anti-GBM antibody response. The initial induction and spontaneous resolution of anti-GBM antibodies were unaffected by depletion of CD8+ T cells. However, CD8-depleted animals were no longer resistant to rechallenge with HgCl2. Cell transfer studies showed that spleen cells from CD8-depleted animals conferred less resistance to HgCl2 than those from animals which had received control antibody. CD8 depletion also reduced the resistance induced by pretreatment with low-dose HgCl2. Studies in which peak sera were pre-incubated with post-recovery sera before testing in a solid-phase anti-GBM radioimmunoassay did not support an important role for anti idiotypic antibodies. We conclude that CD8+ T cells play an important role in the resistance to rechallenge with HgCl2 in the BN rat, although they are not required for the induction or spontaneous resolution of the initial autoimmune response. Demonstration of the reversal of a suppressive phenomenon in vivo using an anti-CD8 monoclonal antibody is unusual. PMID- 1909642 TI - Synovial fluid-derived Yersinia-reactive T cells responding to human 65-kDa heat shock protein and heat-stressed antigen-presenting cells. AB - Humoral and cellular immune reactions to heat-shock proteins have been implicated in the pathogenesis of arthritis. Heat-shock proteins occur in bacteria as well as all eukaryotes and have been highly conserved during evolution. Cross reactivity between bacterial and human heat-shock proteins induced at the site of inflammation may underlie the pathogenesis of some forms of arthritis. In order to test this hypothesis, we raised and cloned a Yersinia-specific T cell line from the synovial fluid lymphocytes of a patient with Yersinia-induced reactive arthritis. From this line we obtained a CD4+ T cell clone that proliferated in response to Yersinia antigens and both to the mycobacterial and the human 65-kDa heat-shock protein. This T cell clone also proliferated in response to autologous heat-stressed antigen-presenting cells as well as to synovial fluid mononuclear cells from the inflamed joint, thus showing true autoreactivity against endogenously synthetized self-antigen. These results demonstrate the induction of an autoimmune T cell response by a natural bacterial infection and support the important role of heat-shock proteins in the pathogenesis of immune-mediated arthritis. PMID- 1909643 TI - Trypanosoma cruzi: infection of T lymphocytes and their destruction by antibody dependent cell-mediated cytotoxicity. AB - We have demonstrated, with optical and transmission electron microscopy, that Trypanosoma cruzi trypomastigotes infect and multiply inside T lymphocytes. The infection rate we have observed in T cells was similar to that seen in the case of macrophage or polymorphonuclear cell infection. Flow cytofluorometric analysis of T lymphocytes purified from mice in the acute phase of the disease, revealed the presence of parasite-derived antigens on their surface. These antigens appear to be specific to T. cruzi and they could be the result of intracellular parasite antigens as well as adsorption of T. cruzi antigens on the surface of noninfected T cells. Antibodies recognizing these surface antigens were present in both T. cruzi-infected mouse and human sera. They were able to induce antibody-dependent cell-mediated cytotoxicity (ADCC) in the presence of nonimmune mononuclear cells both in autologous and in heterologous combinations. Consequently, we provided evidence suggesting that T lymphocytes could be destroyed during the acute phase of Chagas' disease either by cell infection or by an ADCC mechanism against cells bearing parasite antigens on their surface. Thus, the ability of trypomastigotes to invade T cells may play a crucial role in the immunopathogenesis characteristic of Chagas' disease. PMID- 1909644 TI - Differential activity of recombinant lymphokines on mouse B cell proliferation and cell cycle progression are revealed by 5-bromo-2'-deoxyuridine/Hoechst 33258 dye flow cytometry. AB - Activation of resting mouse B cells with anti-mu chain antibodies (anti-mu) leads to cell proliferation. We have investigated the effect of recombinant T cell interleukins (IL 2 to IL 6) on such anti-mu-induced proliferation. No proliferative response was detected when IL 2, IL 3 and IL 6, either alone or in combination with anti-mu, were studied. Furthermore, neither IL 4 nor IL 5 could induce proliferation when added alone to B cell cultures. However, when combined with anti-mu, IL 4 as well as IL 5 stimulated cell growth. Analysis by 5-bromo-2' deoxyuridine/Hoechst 33258 flow cytometry revealed distinct effects of IL 4 and IL 5 on B cell growth. In the presence of anti-mu, both IL 4 and IL 5 co stimulated unfractionated splenic B cells. However, when B cells were separated into subpopulations by density, IL 4 proved to be a cell cycle progression factor, stimulating the majority of resting B cells to enter the cell cycle. In contrast, IL 5 had little effect on the resting fraction of B cells. Rather, IL 5 acted as a co-competence factor, stimulating predominantly low-density B cells. Following exposure of anti-mu alone, most B cells accumulated in the G1 of the second cycle. Upon addition of IL 4, the cells acquired the ability to progress into the next S phase compartment. Contrary to what is seen when B cells are stimulated by other mitogens, very few cells are in the G2 compartments after anti-mu plus IL 4 stimulation. This phenomenon was not due to a differential cell cycle progression rate. Our findings provide an analytical basis for fractionating cell-cycle-compartment-specific B cells for their molecular study. PMID- 1909645 TI - Molecular heterogeneity of auto-anti-idiotypic antibodies in MLR-lpr/lpr mice. AB - The VH and V kappa gene families expressed by 20 monoclonal auto-anti-idiotypes (Ab2) derived from unmanipulated MLR-lpr/lpr mice were determined by Northern blotting. Complete variable region sequences of six Ab2, along with three additional V kappa-JH Ab2 sequences, were obtained. These auto-anti-idiotypes arose spontaneously in the animals, and they bound specifically to an idiotypic determinant (Id/r) on mAb 28/12, a monoclonal IgG2b MLR-lpr/lpr anti-small nuclear ribonucleoprotein antibody. The 16 Ab2 heavy chains belonged to 7 different VH gene families, and the 10 Ab2 light chains were derived from 8 V kappa families. The light chains of two Ab2 were approximately 99% identical; the remaining variable region sequences were highly heterogeneous. There was no correlation between primary amino acid sequence of either heavy or light chain and idiotypic properties of the auto-anti-idiotypes. Six Ab2 used VH or V kappa genes that are identical to known germ-line genes. A high proportion of the spontaneous auto-anti-idiotypes was shown to have autoantibody activity (anti DNA, anti-ribonucleoprotein), or specific binding reactions with lipopolysaccharide of Salmonella RE, or both properties. The structural diversity of spontaneous MLR-lpr/lpr auto-anti-idiotypes differs sharply from the structural homogeneity reported for Ab2 induced in normal animals against syngeneic Ab1. Our results suggest that auto-anti-idiotypes might arise independently of an immunogenic stimulus from an Ab1. PMID- 1909646 TI - Clonal persistence of B lymphocytes in normal mice is determined by variable region-dependent selection. AB - Many adult splenic B cells die within 1 week in the spleen of adoptive adult recipient mice; in contrast, the cellular environment of newborn recipients allows for their expansion and persistence for several weeks. In the present study, we show that the local environment of adult peritoneal cavity also allows adult splenic B cells to persist for over 2 weeks after intraperitoneal transfer. In order to determine whether the persistence of donor B cells in newborn hosts and in the peritoneum of adult recipients results from a selection process involving the clonal specificities expressed, the variation in time of VH gene family repertoires of donor B cells was analyzed in the hosts. At different times after the transfer of splenic cells from lipopolysaccharide (LPS)-reactive mice into LPS-non responder histocompatible recipients, mRNA colony blot assays were performed. The results show that among the donor adult LPS-reactive B cells, the VH genes are differently used by the expanding or persisting B cells, in both kinds of recipients. Thus, cells expressing J558 or VH11 gene families are, in particular, positively selected, while those expressing D-proximal or J606 and 36 30 VH gene families are less selected. These findings demonstrate that the propensity of B cells to persist and expand is determined by their selection through their immunoglobulin variable regions, rather than by genetic properties linked to particular B cell subsets. PMID- 1909647 TI - Differential migration of T and B cells during an acute inflammatory response. AB - Inflammation in the liver and mammary glands of sheep caused by challenge infection with Taenia hydatigena or infusion of killed Staphylococcus aureus, respectively were characterized by the recruitment of both T and B cells. The patterns of migration of these two major lymphocyte subpopulations were distinctly different. While T cells seemed to migrate out of existing, flat endothelium-lined blood vessels resulting in a diffuse distribution at the sites of inflammation, B cells were characteristically present as clusters of tightly packed cells at restricted sites in the inflamed tissue. Within these B cell clusters distinct capillary vessels lined with plumb endothelial cells were always present suggesting that they were the sites of intense migration of B cells originating from the draining lymph nodes. These results indicate differential regulation of adhesion molecules on B and T cells and/or their ligands on endothelium during acute inflammatory reactions. PMID- 1909648 TI - Germ-line origin of functional idiotypic interactions: identification of two idiotypically connected, natural antibodies that are encoded by germ-line gene elements. AB - Two monoclonal, natural IgM antibodies derived from normal BALB/c mice were selected on the basis of being idiotypically complementary and functionally connected. Nucleotide sequence analysis of their respective heavy and light chain V regions showed that both of the clones expressed VH, D, JH, VL and JL gene segments of germ-line origin. Furthermore, none of the clones displayed N sequence additions. These data suggest a germ-line origin of a functional idiotypic network and confirm a minimized contribution of somatic diversification through template-independent addition of N-nucleotides in neonatal B cell repertoires. PMID- 1909649 TI - Trypanosoma cruzi: T-cell-dependent mechanisms of resistance during chronic infection. AB - Effector mechanisms of resistance exerted by T cells from BALB/c mice chronically infected with Trypanosoma cruzi, Tulahuen strain, were studied. Spleen cells from chronically infected mice (Chro-SC) prestimulated with heat-killed trypomastigotes (HKT) and/or IL-2 destroyed PHA-labeled p-815 mastocytoma cells, HKT-pulsed macrophages, and normal peritoneal macrophages. However, HKT stimulated Chro-SC did not affect the infectivity of free bloodstream forms of the parasite. Upon HKT stimulation, Chro-SC or their culture supernatant activated peritoneal macrophages for the destruction of intracellular amastigotes. The effect was abolished after Thy 1.2+ cell depletion. The addition of Cyclosporin A (CyA), which blocks T-cell activation, during HKT-stimulation of Chro-SC, diminished their ability to activate the trypanocidal activity of macrophages. CyA also inhibited the production of both macrophage-activating factors and interferon-gamma by HKT-stimulated Chro-SC. CyA administration to recipients of nylon-wool nonadherent spleen cells from chronically infected mice inhibited their adoptively acquired resistance against T. cruzi, suggesting that the conferred resistance depended on the effect of specifically activated cells. When administered during the chronic stage of the infection, CyA abrogated the antigen-specific delayed type hypersensitivity response but increased the levels of anti-T. cruzi IgG antibodies. Neither parasitemia, tissular parasitism in myocardium or skeletal muscle, nor mortality were detected after CyA treatment, suggesting the presence of a CyA nonsensitive mechanism(s) in the control of T. cruzi during the chronic phase of the infection. PMID- 1909650 TI - Lack of effect of epidermal growth factor on radiolabelled diacylglycerol in rat parietal cells. PMID- 1909651 TI - Protein kinase C-dependent and -independent actions of arachidonic acid in GH3 cells. PMID- 1909652 TI - Does inositol hexakisphosphate induce Ca2+ entry into GH3 cells? PMID- 1909653 TI - The identification of protein-RNA interactions within the 5' untranslated region of human preproinsulin mRNA. PMID- 1909654 TI - A rapid bioassay technique for arginine-vasopressin. PMID- 1909655 TI - Reductive activation of N-oxides to cause DNA strand breakage in cell lines in vitro. PMID- 1909656 TI - Muscle pH recovery after high intensity cycle exercise in malignant hyperthermia susceptible subjects. PMID- 1909657 TI - Apparent calcium-independent phorbol ester binding to protein kinase C. PMID- 1909658 TI - Inositol hexakisphosphate-membranes interactions: the role of metal ions. PMID- 1909659 TI - Effects of prolonged treatment of adipocytes with PGE1, N6-phenylisopropyl adenosine and nicotinic acid on G-proteins and antilipolytic sensitivity. PMID- 1909660 TI - A possible role for eicosanoids in ATP-induced plasma membrane bleb formation in isolated hepatocytes. PMID- 1909661 TI - High Mn2+ sensitivity of vesicular galactosyltransferase in thymus and mammary gland. PMID- 1909662 TI - Specific immunodetection of G-proteins in plant cell membranes. PMID- 1909663 TI - Antigen processing and class II MHC-restricted antigen presentation in B lymphocytes. PMID- 1909664 TI - Long-term proliferating early pre-B-cell lines and clones with the potential to develop to surface immunoglobulin-positive, mitogen-reactive B-cells in vitro and in vivo. PMID- 1909665 TI - Avian G-protein-regulated phospholipase C. PMID- 1909666 TI - Is arachidonic acid a retrograde messenger in long-term potentiation? PMID- 1909667 TI - Mutations in Gs alpha that alter the kinetics of guanine nucleotide binding and hydrolysis. PMID- 1909668 TI - Circadian oscillations in protein and mRNA levels of the period gene of Drosophila melanogaster. PMID- 1909669 TI - Phorbol esters trigger the inactivation of the inhibitory quanine-nucleotide binding regulatory protein (Gi) in airway smooth muscle. PMID- 1909670 TI - Effects of lipoxin A4 on cytosolic calcium in human neutrophils. PMID- 1909671 TI - Gi function in the streptozotocin-treated diabetic rat liver. PMID- 1909672 TI - Prostanoid-mediated downregulation of Gs in NG108-15 cells. PMID- 1909673 TI - U937 cell differentiation: G protein alterations and interaction with the chemotactic peptide receptor. PMID- 1909675 TI - [Glassy cell carcinoma of the cervix]. AB - Glassy cell carcinoma of the cervix is a rare carcinoma with rapid progression and early metastasis. The aggressive course of a glassy cell carcinoma of the cervix in Stage Ib (FIGO) of a 24-year-old woman could neither be markedly influenced by radical hysterectomy, nor by chemotherapy and radiation. The patient died ten months after diagnosis. PMID- 1909676 TI - Genetic and molecular analyses of vgal: a spontaneous and unstable mutation at the vestigial locus in Drosophila melanogaster. AB - We describe herein, a new unstable mutant of the vestigial locus, isolated from a French natural population. From this mutant vestigial almost (vgal) wild-type flies (vgal+) and extreme vg phenotypes (vge) arose spontaneously without genomic shock. The occurrence of vgal+ or vge alleles depends mostly on the breeding temperature; vgal+ revertants arose principally at low temperature (21 degrees C) and vge at 28 degrees C. These events occur mainly in the male germ line and the phenomenon appears to be premeiotic. Our results with in situ hybridization experiments and Southern blots show that the vgal mutation is due to a 2 kb DNA insertion, which is a deleted hobo element. Genetic and molecular analyses show that two distinct events may underly the wild-type revertants. One is the excision of the resident hobo element, the other a further deletion (about 300 bp in the example characterized herein). The vge mutation is probably due to a deletion of vestigial sequences flanking the hobo insertion. PMID- 1909674 TI - Analysis of neutral amino acid transport systems in the small intestine: a study of brush border membrane vesicles. AB - Transport of L-proline, L-leucine and L-cysteine was studied in brush border membrane vesicles prepared from guinea pig ileum. Concentrative transport of L proline, L-leucine and L-cysteine was obtained in the presence of an Na+ gradient from, outside to inside of the vesicles, which indicated contribution of either system A (alanine-preferring) or system ASC (alanine-, serine- and cysteine preferring) to the transport. When Na+ was replaced by Li+, L-leucine and L cysteine maintained the same concentrative transport. However, the concentrative transport of L-proline was markedly decreased by Li+ -for-Na+ substitution. Strong exchange properties of L-leucine transport via system L (leucine preferring) was observed with brush border membrane vesicles, in which preloaded L-methionine could be exchanged with labeled L-leucine added outside the vesicles. These results suggest that the small intestine of the guinea pig possesses classical neutral amino acid transport systems such as systems A, ASC and L. PMID- 1909678 TI - Tissue specific effects of ommochrome pathway mutations in Drosophila melanogaster. AB - The tissue-specific effects of 17 mutations affecting the synthesis of brown eye pigment (xanthommatin) have been investigated by combining them with chocolate and red cells, two mutations causing ectopic pigmentation of the Malpighian tubules and larval fat body (which normally only synthesize pigment precursors). The majority of mutations block the pigmentation of four organs; the normally pigmented eyes and ocelli, and ectopically pigmented tubules and fat body. They represent genes that would appear to be required for the normal operation of the pathway per se and are likely to encode structural proteins. Mutations at 5 loci affect pigmentation of a subset of organs: cd and po affect only the eyes and ocelli; kar affects the eyes, ocelli and fat body; car causes excretion of pigment from tubules; and z affects pigmentation of the eyes alone. Of these loci, only z has been shown to encode a regulatory protein and the role of the remaining four gene products is not clear. Two mutations affecting the red eye pigments (drosopterins), bw and mal, do not substantially perturb brown pigment synthesis in any of the four organs. PMID- 1909677 TI - Nucleolus organizer-suppressed position-effect variegation in Drosophila melanogaster. AB - The white locus is inactivated in a cell-by-cell variegated pattern when juxtaposed with the proximal or distal parts of the nucleolus organizer region (NO) by X chromosome inversion. Recombinants for two such inversions, wm51b and wm4, were obtained and randomized for genetic background. White locus activity was much higher in the wm4 recombinant duplicated for most of the NO and much lower in the wm51b recombinant deficient for it. Although there may be other molecular differences between the heterochromatic regions of the recombinants, the most obvious is the dosage of NO. Suppression of a NO region-evoked variegated phenotype by additional NO doses is discussed in relation to four different classes of models for position-effect variegation (PEV): chromatin structure, nuclear geometry, incomplete transposition of mobile elements, and heterochromatin promoter-driven transcription. A corollary of the structural model is functional subdivision of heterochromatin, which would enable the use of PEV as a tool for its study. PMID- 1909679 TI - Fertility and viability at the Sod locus in Drosophila melanogaster: non-additive and asymmetric selection. AB - Experiments were designed to test in Drosophila melanogaster the effect of mating type at the Sod locus on fertility and viability. The experiments show that fertility is neither additive (or multiplicative) nor symmetric, i.e. that the fertility of a mating type cannot be predicted from the average fertility of the two genotypes involved in the mating. There is no significant male x female interaction with respect or progeny viability; but the interaction is significant for productivity, i.e. when fertility and viability are jointly taken into account. There is overdominance with respect to female fertility, but not with respect to male fertility or to viability. There also is alloprocoptic selection with respect to fertility and with respect to productivity, i.e. mating between like homozygotes are less fertile and productive than matings between dissimilar homozygotes. Selection at the Sod locus yields stable polymorphic equilibria, with the frequency of the F allele predicted at P = 0.641 or 0.695, respectively for low and high larval density. PMID- 1909681 TI - Sequence of the precursor of intestinal lactase-phlorizin hydrolase from fetal rat. AB - The nucleotide sequence of the cDNA corresponding to the precursor of fetal rat intestinal lactase-phlorizin hydrolase was determined. The precursor consists of four tandemly organized homologous domains flanked by a signal peptide in the N terminal region and by a transmembrane peptide in the C-terminal region. PMID- 1909680 TI - Drosophila melanogaster diphenol oxidase A2: gene structure and homology with the mouse mast-cell tum- transplantation antigen, P91A. AB - The Drosophila melanogaster diphenol oxidase (DOX) A2-encoding gene (Dox-A2) is involved in catecholamine metabolism, melanin formation and sclerotization of the cuticle. Insect phenol oxidases (POX) are well studied biochemically, but not genetically and molecularly. The Dox-A2 (2-53.9) gene is the first insect POX encoding gene to be cloned and sequenced. It encodes a protein product unique among currently known POX. The deduced protein, however, exhibits extensive similarity (58-81%) to the mouse mast cell tum- antigen, P91A [Lurquin et al., Cell 58 (1989) 293-303] and may identify the normal mouse protein as a DOX. PMID- 1909682 TI - 'Heroic' measures for elderly patients. PMID- 1909683 TI - Isolation of probes specific to human chromosomal region 6p21 from immunoselected irradiation-fusion gene transfer hybrids. AB - A hybrid cell line (R21/B1) containing a truncated human chromosome 6 (6pter 6q21) and a human Y chromosome on a hamster background was irradiated and fused to A23 (TK-) or W3GH (HPRT-) hamster cells. Clones containing expressed HLA class I genes (4/40) were selected using monoclonal antibodies. These clones were recloned and analyzed with a panel of probes from the HLA region. One hybrid (4G6) contained the entire HLA complex. Two other hybrids (4J4 and 4H2) contained only the HLA class I region, while the fourth hybrid (5P9) contained HLA class I and III genes in addition to other genes located in the 6p21 chromosomal region. In situ hybridization showed that the hybrid cells contained more than one fragment of human DNA. Alu and LINE PCR products were derived from these cells and compared to each other as well as to products from two somatic cell hybrids having the 6p21 region in common. The PCR fragments were then screened on conventional Southern blots of the somatic cell hybrids to select a panel of novel probes encompassing the 6p21 region. In addition, the origin of the human DNA fragments in hybrid 4J4 was determined by regional mapping of PCR products. PMID- 1909684 TI - New markers for the neurofibromatosis-2 region generated by microdissection of chromosome 22. AB - To identify new DNA markers around the neurofibromatosis-2 gene on human chromosome 22, the critical region (22q12-q13.1) was microdissected and microcloned from GTG-banded metaphase chromosomes. Eighteen thousand recombinant clones were obtained. Twenty-seven of 55 clones tested (50%) detected single-copy DNA sequences. Nine of nine clones analyzed in detail were found to map to chromosome 22. Interestingly one clone (EAN04) is part of the leukemia inhibitory factor gene which has previously been mapped to 22q11.2-q13.1. Four clones (EAN01, EAN47, EAN57, and EAN68) detect DNA polymorphisms. These probes were used to compare constitutional and tumor genotypes of 41 patients with acoustic neurinoma. Loss of constitutional heterozygosity was identified in 17 of 31 informative cases (55%). From our data we conclude that the microdissection library is a valuable resource for physical and genetic mapping studies in neurofibromatosis-2. PMID- 1909685 TI - Evolution and distribution of (GT)n repetitive sequences in mammalian genomes. AB - The dinucleotide repetitive sequence, (GT)n, is highly interspersed in eukaryotic genomes and may have functional roles in genetic recombination or the modulation of transcriptional activity. We have examined the distribution and conservation of position of GT repetitive sequences in several mammalian genomes. The distribution of GT repetitive sequences in the human genome was determined by the analysis of over 3700 cosmid clones containing human insert DNA. On average, a GT repetitive sequence occurs every 30 kb in DNA from euchromatic regions. GT repetitive sequences are significantly underrepresented in centric heterochromatin. The density of GT repetitive sequences in the human genome could also be estimated by analyzing GenBank genomic sequences that include introns and flanking sequences. The frequency of GT repetitive sequences found in GenBank human DNA sequences was in close agreement with that obtained by experimental methods. GenBank genomic sequences also revealed that (GT)n repetitive sequences (n greater than 6) occur every 18 and 21 kb, on average, in mouse and rat genomes. Comparative analysis of 31 homologous sequences containing (GT)n repetitive sequences from several mammals representing four orders revealed that the positions of these repeats have been conserved between closely related species, such as humans and other primates. To a lesser extent, positions of GT repetitive sequences have been conserved between species in distantly related groups such as primates and rodents. The distribution and conservation of GT repetitive sequences is discussed with respect to possible functional roles of the repetitive sequence. PMID- 1909686 TI - FSH, inhibin and other bioactive peptides of male genital tract: localization, synthesis and their role in cellular pathophysiology. PMID- 1909687 TI - Opportunities to improve the cost-effectiveness of treatment for hypertension. AB - The cost-effectiveness of treatment for hypertension depends on the pretreatment level of blood pressure, age and sex of the patient, presence of other cardiovascular risk factors, long-term control of blood pressure, and the annual costs of treatment. Treatment of very mild hypertension (diastolic blood pressure, 90-94 mm Hg), even if the benefits do exceed the risks, does not appear to be particularly cost-effective. Opportunities to improve the cost effectiveness of hypertension management lie in 1) avoidance of patient mislabeling by careful documentation of blood pressures on multiple occasions in the office and during usual activities outside the office before the diagnosis is made and treatment is begun; 2) efforts to increase adherence to scheduled visits and medication regimens; 3) attempts to step-down dosages or discontinue medications after periods of good blood pressure control; 4) explicit consideration of costs, as well as benefits, in decisions on the needed frequency of office visits, choice of medications, and use of laboratory tests; and 5) efforts to improve practice efficiency. Future practice guidelines for hypertension management should take these factors into account and should make trade-offs between benefits, risks, and costs explicit for specific types of patients. PMID- 1909688 TI - Bactericidal effect of penicillin, ampicillin, and amoxicillin alone and in combination with tobramycin against Enterococcus faecalis as determined by kill kinetic studies. AB - Fifteen strains of Enterococcus faecalis, all clinical blood culture isolates from patients with endocarditis, were studied by kill-kinetic experiments using penicillin G, ampicillin and amoxicillin alone and in combination with tobramycin. The median minimal inhibitory concentrations (MIC), were penicillin 4 mg/l, ampicillin 2 mg/l, amoxicillin 2 mg/l and tobramycin 32 mg/l. Equipotent doses of the antibiotics (1/2 x MIC, 1 x MIC and 4 x MIC) were used in the kill kinetic studies. Synergism was studied using a combination of 1/2 x MIC of the beta-lactam antibiotic and 8 mg/l of tobramycin. The bactericidal activity did not exceed 10(+3) cfu/ml at 5 hours for any single compound. After 5 h all three beta-lactam antibiotics in combination with tobramycin resulted in synergism, i.e. more than one hundredfold reduction of colony forming units (cfu) as compared to the most active single agent. Amoxicillin had a significantly higher bactericidal potential than ampicillin or penicillin both alone and in combination with tobramycin. The clinical significance of these findings warrants further studies in vivo. PMID- 1909689 TI - Smoking effect on exercise response kinetics of oxygen uptake and related variables. AB - The effects of smoking on the kinetics of oxygen uptake (VO2), carbon dioxide production (VCO2), ventilation (Ve) and heart rate (HR) in the transition from rest to steady-state submaximal exercise was investigated in 6 female and 4 male smokers (32 +/- 8 yrs). The subjects underwent two counter-balanced treadmill tests at 60% of their maximal VO2, lasting 10 min each: one following a 24-hr smoking abstinence, and one immediately after smoking three cigarettes without prior abstinence. Physiological variables were measured at rest and every 30 sec throughout each test. The time required for a given variable to rise from its respective resting baseline to half of its steady-state value (t1/2) was calculated for VO2, VCO2, Ve and HR. Smoking abstinence was associated with t1/2 values of 32 +/- 8, 42 +/- 12, 43 +/- 10, and 30 +/- 9 sec for VO2, VCO2, Ve, and HR, respectively. Smoking significantly (p less than 0.01) lengthened those values to 51 +/- 12, 58 +/- 11, 54 +/- 8, and 41 +/- 10 sec. Concurrently, smoking raised the baseline (resting) values of HR (p less than 0.01) and of Ve, VCO2, O2 pulse (O2P), and both systolic and diastolic blood pressures (p less than 0.05). During steady-state exercise only HR values were elevated by smoking (p less than 0.01), while O2P values were lowered (p less than 0.05). These findings indicate that smoking considerably retards physiological responses to submaximal exercise. PMID- 1909690 TI - Beta-lactamase production and bacterial tolerance in recurrent acute otitis media. AB - Different reasons for treatment failure or relapse of acute otitis media (AOM) have been suggested. In this study 38 children (8 treatment failures, 13 relapses of AOM within one month and 17 with a new AOM) were compared to 25 matching healthy children, regarding beta-lactamase producing bacteria and tolerance to penicillin V and ampicillin. Branhamella catarrhalis was the most common bacteria found in the nasopharynx and was isolated in 60% of children with AOM and in 48% of the control group. Fifty-two percent of the children classified as treatment failure or relapse of AOM had aerobic beta-lactamase producing bacteria in NPH. No bacteria tolerant to penicillin or ampicillin were found. Thus, beta-lactamase producing bacteria seem to play a decisive role in treatment failure and relapse of AOM. On the other hand, tolerance to penicillin V or ampicillin does not seem to have any impact on healing of AOM. PMID- 1909691 TI - Changes in parameters of the coagulation-fibrinolysis system and platelet function after OKY-046 administration to patients with ruptured aneurysm of the cerebral artery. AB - The influence of the TXA2-synthetase inhibitor OKY-046 (Xanbon) on haematological findings for the coagulation-fibrinolysis system and platelet aggregation was investigated in patients with subarachnoid bleeding during or after the administration. Changes in alpha 2-PI activity and the levels of fibrinogen, t-PA and PAI antigen were observed. Especially, PAI activity and PAI antigen were found to be significantly increased as compared with levels before the administration. On the other hand, the platelet aggregation induced by various agents and the activity of AT-III were not greatly altered after the administration of OKY-046. PMID- 1909692 TI - Effect of cyclosporine A on circulating immune complexes in IgA nephropathy. AB - This work was undertaken to examine the effect of cyclosporine A (CyA) on the serum concentration of circulating immune complexes in 22 patients with IgA nephropathy during an infection-free period. They were randomly divided into 2 groups: 11 patients received oral cyclosporine A (5 mg/kg/day) for 12 weeks and 11 patients received placebo (0.05 ml/kg/day). A significant reduction of proteinuria was observed in patients on CyA therapy but not in those receiving placebo. IgG-circulating immune complexes (CIC) were determined by solid phase Clq enzyme immunoassay (Clq EIA) and radial immunodiffusion (RID) and IgA-CIC were determined by solid phase anti-C3 enzyme immunoassay (anti-C3 EIA) and radial immunodiffusion. There was no change in IgA-CIC measured by RID and anti C3 EIA after 12 weeks of CyA therapy. Similarly, changes in IgG-CIC were not demonstrated with CyA therapy. No apparent decrease in IgG-CIC or IgA-CIC was observed with placebo treatment. Our study suggests that immunomodulation by CyA therapy does not affect the IgA-CIC and IgG-CIC levels in patients with IgA nephropathy. PMID- 1909693 TI - [Early results of transversalis-plasty. A prospective randomized comparison of non-resorbable and resorbable sutures]. AB - In a prospective randomized trial we analyzed the perioperative management, complications, and the recurrence rate of inguinal hernia repair using either resorbable (polydioxanone, PDS) or non-absorbable (polyamide, Ethilon) suture material. From January 1988 to June 1989, 484 consecutive transversalis fascia repairs were performed in 425 adult patients with inguinal or femoral hernia. Local anaesthesia was used in 273 cases. At least one year postoperatively, 390 patients with 445 repairs had a clinical follow-up. The recurrence rate after 360 primary herniae was 3.3% (Ethilon 2.3%, PDS 4.3%) while 5.9% rerecurrences were found following operation for recurrent hernia (Ethilon 2.5%, PDS 8.9%). The differences in the recurrence rates following the use of polyamide or polydioxanone were not statistically significant. Complications occurred in 5.2%. The postoperative hospital stay averaged 3.8 days and work was resumed after a mean of 3.9 weeks. PMID- 1909694 TI - HLA class II nucleotide sequences, 1991. PMID- 1909695 TI - Otitis media/interna and suppurative meningoencephalomyelitis associated with Listeria monocytogenes infection in a llama. AB - Listeria monocytogenes was found to be the cause of fatal suppurative meningoencephalomyelitis in a 3.5-month-old cria. The cria initially had clinical signs of unilateral peripheral vestibular disease, but on the following day, the cria developed progressive signs of encephalitis. Treatment with antibiotics, flunixin meglumine, and anticonvulsant drugs failed to stop progression of the disease, and the cria was euthanatized. Post-mortem examination revealed otitis media-interna and diffuse suppurative meningoencephalomyelitis. Listeria monocytogenes was isolated from CSF and brain tissue. PMID- 1909696 TI - Evaluation of components of residential treatment by Medicaid ICF-MR surveys: a validity assessment. AB - We evaluated the proficiency of the federal Medicaid program's survey process for evaluating intermediate care facilities for the mentally retarded. In Study 1, an observational analysis of active treatment during leisure times in living units suggested that these surveys did not discriminate between certified and noncertified units. In Study 2, a reactivity analysis of a survey indicated that direct-care staff performed differently during the survey by increasing interactions with clients and decreasing nonwork behavior. Similarly, results of Study 3 showed increases in client access to leisure materials during a survey. In Study 4, questionnaire results indicated considerable variability among service providers' opinions on the consistency, accuracy, and objectivity with which survey teams determine agency standard compliance. Results are discussed regarding effects of the questionable proficiency of survey processes and the potential utility of behavioral assessment methodologies to improve such processes. PMID- 1909697 TI - Acute changes of systemic parameters in tumour-bearing rats, and of tumour glucose, lactate, and ATP levels upon local hyperthermia and/or hyperglycaemia. AB - Arterial blood pressure and relevant parameters of the arterial blood (O2 and CO2 tensions, pH, haematocrit, serum electrolytes and osmolality) were determined in tumour-bearing rats upon local hyperthermia (HT) and/or hyperglycaemia (HG). Tumour heating was performed in a saline bath (44 degrees C) for 120 min; hyperglycaemia was induced by i.v. infusion of 40% glucose solution for 150 min [blood glucose levels: 35-40 mM during heating; total amount of glucose: 1.19 g/100 g body wt.; infusion rates: 0.31 ml (100 g body wt.)-1 min-1 for 2 min, 0.02 ml (100 g body wt.)-1 min-1 for 88 min, and 0.01 ml (100 g body wt.)-1 min-1 for 60 min]. Immediately after treatment, glucose, lactate and ATP levels were determined in tumour and muscle specimens and compared to these values under normothermic (NT) and/or normoglycaemic (NG) conditions. In all groups (NT/NG, NT/HG, HT/NG, HT/HG) there were only minor but characteristic changes in blood parameters, which were mainly due to the volume and type of the infused fluids (glucose solution, saline). During hyperglycaemia, tumour glucose levels rose 13- to 17-fold, whereas muscle glucose concentrations exhibited only a 3- to 5-fold increase; lactate levels were 1.9-2.5 times higher in tumours than in muscle, indicating an increase in the metabolic differences between normal and malignant tissues. Despite an increased glucose availability, tumours did not show an improved energy status and, thus, would not be expected to develop a decrease in thermal sensitivity or stimulation in growth rate. The good systemic tolerability of the combined treatment (HT/HG) and the differential changes in malignant and normal tissue occurring under these conditions, support further attempts to manipulate tumour metabolic environment by glucose in order to achieve better therapeutic results. PMID- 1909698 TI - Cepharanthine inhibits two-stage tumor promotion by 12-O-tetradecanoylphorbol 13 acetate and mezerein on skin tumor formation in mice initiated with 7,12 dimethylbenz[a]anthracene. AB - Cepharanthine, isolated from Stephania cepharantha, is one of the bisbenzylisoquinoline-type alkaloids. We have found that it inhibits tumor promotion after topical application in two-stage carcinogenesis in mouse skin. Epidermal ornithine decarboxylase activities inhibited by topical application of cepharanthine, with an 5 micrograms/mouse) and mezerein (5 micrograms/mouse) were found to be inhibited by topical application of cepharanthine, with a ED50 of 1.2 mumol and 1.4 mumol respectively. These inhibitory effects of cepharanthine are considered to be related to its antitumor activity in two-stage carcinogenesis in mouse skin. Cell-mediated immunosuppression by TPA was unaffected by topical application of cepharanthine. A diet containing 0.005% cepharanthine (about 0.5 mg mouse-1 day-1) slightly suppressed the two-stage promotion of skin tumors by twice-weekly applications of 2.5 micrograms TPA for 2 weeks (first stage) followed by twice-weekly applications of 2.5 micrograms mezerein for 23 weeks (second stage) in ICR mice following initiation by 50 micrograms 7,12 dimethylbenz[a]anthracene. Oral administration of cepharanthine inhibits the tumor promotion in two-stage carcinogenesis in mouse skin. PMID- 1909700 TI - Placebo-controlled double-blind comparative study on the preventive efficacy of mesna against ifosfamide-induced urinary disorders. AB - In order to evaluate the preventive efficacy, safety and usefulness of mesna (Sodium 2-mercaptoethane sulfonate) against ifosfamide-induced urinary disorders, a placebo-controlled double-blind comparative study was performed. Ifosfamide was administered by intravenous drip infusion at a daily dose of 2 g/m2 for 5 consecutive days, and mesna was intravenously administered at 20% of the ifosfamide dose, three times daily for 5 consecutive days. The results obtained are as follows. (a) Of 101 accrued patients, 91 patients were evaluated consisting of 45 for the mesna group and 46 for the placebo group. There was no intergroup difference in the number of the evaluated cases and patient characteristics. (b) Micturition pain and feeling of residual urine graded as moderate or severe were not observed for the mesna group, but were observed for the placebo group with incidences of 19.6% (9/46) for micturition pain and 15.2% (7/46) for feeling of residual urine; the intergroup differences in the appearance of these urinary symptoms were statistically significant (P = 0.0003 for micturition pain; P = 0.0009 for feeling of residual urine). The incidence of hematuria graded as moderate or severe was 6.7% (3/45) in the mesna group, which was significantly lower than the 32.6% (15/46) in the placebo group (P = 0.0008). (c) No side-effect attributable to mesna was observed. (d) A judgment of "useful" was obtained in 80.0% (36/45) of the patients treated with mesna, which was significantly higher than the 34.8% (16/46) of the patients treated with placebo (P = near 0). On the basis of the above results, we conclude that the preventive efficacy, safety and usefulness of mesna against ifosfamide-induced urinary disorders have been well demonstrated in this study. PMID- 1909699 TI - High release of tumor necrosis factor alpha, interferon gamma and interleukin-6 by adherent lymphokine-activated killer cells phenotypically derived from T cells. AB - Adherent lymphokine-activated killer cells (A-LAK) are highly potent cytotoxic cells, which are shown to be derived not only from natural killer (NK)/K cells but phenotypically also from T cells. The generation and phenotypical and functional characterisation of these T-cell-derived A-LAK are described. In contrast to non-adherent cells (NA-LAK) and unseparated LAK (UN-LAK), these mostly CD3+ CD56+ CD8+ cells display a high degree of expansion following initial interleukin-2 (rIL-2) activation and further culturing in autologous conditioned medium. A comparison of cytotoxic activities of cultured cells reveals a significantly higher oncolytic ability of A-LAK cells against both K562 and Daudi cells than that of cultured controls of NA-LAK and UN-LAK. In addition, A-LAK are characterised by a marked endogenous cytokine release of interferon gamma, tumour necrosis factor alpha and IL-6 as well as by their shedding of p55 IL-2 receptor after exposure to IL-2. The results demonstrate A-LAK to be the lymphocyte subpopulation with the most cytotoxic activity and endogenous cytokine release after exposure to IL-2. The improvement of techniques for long-term cultures may be of interest for future therapeutic approaches. PMID- 1909702 TI - High levels of serum soluble interleukin-2 receptors in hyperthyroid patients: correlation with serum thyroid hormones and independence from the etiology of the hyperthyroidism. AB - The serum levels of soluble interleukin-2 receptors (s-IL-2R) and soluble CD8 antigens (s-CD8) were measured in 33 patients with Graves' disease (GD), 29 with toxic nodular goiter (TNG), 6 with toxic adenoma (TA), and 12 with hypothyroidism, as well as in 11 patients with infectious mononucleosis (known to have high s-IL-2R and s-CD8 levels) and 34 normal controls. Serum levels of T3 and T4, both total and free, and of TSH were simultaneously determined. s-IL-2R levels were significantly higher in all patients with hyperthyroidism (mean +/- SD, 3276 +/- 1273 U/mL for GD, 4183 +/- 1832 for TNG, and 1671 +/- 648 for TA) compared to normal control values (P less than 0.001 for GD and TNG and P less than 0.01 for TA), while in the euthyroid state they were within the normal range (535 +/- 240 U/mL). Hypothyroid patients had significantly lower s-IL-2R levels compared to normal controls (P less than 0.05). A positive correlation (P less than 0.001) between serum s-IL-2R levels and total/free T3-T4 levels was found in these groups of patients, while no correlation between s-CD8 levels and s-IL 2R/T3/T4 was found. These findings suggest an association between hyperthyroxinaemia and activation of human lymphocytes in vivo. PMID- 1909701 TI - Suppression of the pituitary-gonadal axis in children with central precocious puberty: effects on growth, growth hormone, insulin-like growth factor-I, and prolactin secretion. AB - To assess further the relationship between gonadal sex steroids and PRL, GH, and insulin-like growth factor-I (IGF-I) secretion and to help clarify the mechanism underlying the pubertal growth spurt, we studied 11 children (10 girls) with central precocious puberty before and during gonadal suppression with the GnRH agonist (GnRH-a) leuprolide acetate. Nocturnal sampling for plasma levels of GH and PRL, GH response to GH-releasing factor-(1-44), and plasma IGF-I levels were determined before and 3-6 months after pituitary-gonadal suppression. Treatment caused a significant decrease in the LH and FSH responses to GnRH (P less than 0.01) and the plasma concentration of estradiol (P less than 0.05). The patients' mean height velocity SD score for chronological age, initially 3.8 +/- 1.9, decreased significantly to 0.9 +/- 0.9 with treatment (P less than 0.005). Nocturnal GH secretion (mean GH concentration, sum of GH pulse areas, sum of GH pulse amplitudes, and GH pulse frequency) and mean IGF-I levels (1.38 +/- 0.6 vs. 1.72 +/- 0.34 U/mL) were not significantly altered by treatment. However, the mean peak GH response to GH-releasing factor-(1-44) was 29.2 +/- 6.8 micrograms/L before treatment and declined significantly to 17.7 +/- 3.4 micrograms/L after gonadal suppression (P less than 0.05). PRL secretion was similar before and after GnRH-a-induced suppression. These results indicate that the decrease in height velocity noted during GnRH-a treatment occurred independently of changes in nocturnal GH secretion and IGF-I levels. These data are consistent with the premise that sex steroids can modulate growth by a direct action on skeletal growth. PMID- 1909703 TI - Serum melatonin in central precocious puberty is lower than in age-matched prepubertal children. AB - In children a progressive decrease in nocturnal serum melatonin (MT) has been shown with advancing age, suggesting a reduction in the amplitude of the circadian MT curve with maturation. Whether this alteration of MT levels is related to human sexual maturation or occurs independently remains to be elucidated. Also, the impact of gonadal steroids on the MT rhythm remains an open question. We examined 56 patients (51 females and 5 males) with central precocious puberty (52 idiopathic and 4 neurogenic). Patients were studied before and 3, 6, and 12 months after initiation of GnRH analog treatment. Three hundred and thirty-seven endocrinologically normal subjects (190 males and 147 females) served as controls. In all subjects nocturnal serum MT (blood collection between 2300 and 0100 h) was measured with a highly specific RIA. In young patients, aged 1-5 yr, we found significantly lower MT levels than in age-matched controls. Pubertal patients, aged 5-9 yr, displayed nocturnal MT levels in the same range as control subjects approaching normal pubertal age. In contrast to endocrinologically normal children, there was no age-dependent decrease in nocturnal MT in untreated precocious puberty; rather, it appeared that serum MT had already declined in association with the onset of sexual maturation. Although there was a significant difference in weight between patients and age-matched controls, the low MT values in patients 1-5 yr old were only partly explained by the weight difference (P less than 0.0009); their pubertal status also contributed significantly (P less than 0.006). Pituitary-gonadal suppression induced by long term GnRH analog treatment did not result in a return to prepubertal MT levels; rather, nocturnal MT decreased during therapy. The collected data indicate that nocturnal serum MT levels are related to sexual maturation, since serum MT is similar in precocious puberty and normal pubertal children. Since suppression of the pituitary-gonadal axis did not result in increases in nocturnal MT levels in young patients with precocity (i.e. return to age-appropriate levels), the reduction of nocturnal MT with normal puberty is not likely to be dependent on pubertal gonadotropin or sex steroid milieu. PMID- 1909704 TI - Serum progesterone levels predict success of in vitro fertilization/embryo transfer in patients stimulated with leuprolide acetate and human menopausal gonadotropins. AB - Serum progesterone (P4) levels greater than 2.86 nmol/L (0.9 ng/mL) on the day of hCG administration are reportedly associated with decreased pregnancy rates in in vitro fertilization/embryo transfer (IVF/ET) cycles. To further assess this phenomenon we measured serial serum P4, LH, and estradiol levels in 115 consecutive patients undergoing stimulation for IVF/ET with midluteal leuprolide acetate and human menopausal gonadotropins. IVF/ET cycle outcome was retrospectively correlated with P4 levels on the day of hCG administration. Two critical breakpoints were identified, 1.27 nmol/L (0.4 ng/mL) and 286 nmol/L (0.9 ng/mL). Clinical pregnancies occurred in 9 of 18 patients in group I (P4, less than 1.27 nmol/L) compared to 11 of 81 patients in group II (1.27 less than P4 less than 2.86 nmol/L; P = 0.001) and 0 of 14 patients in group III (P4, less than or equal to 2.86 nmol/L) (P = 0.001). Eleven patients in group III had cryopreservation of embryos during that cycle. Six subsequently underwent frozen embryo transfer, and clinical pregnancies occurred in 2, both of whom have delivered. These findings demonstrate that even modest increases in serum P4 levels (greater than 1.27 nmol/L) are associated with reduced pregnancy rates in IVF/ET cycles. In addition, it appears that the mechanism may not exclusively involve poor oocyte quality. PMID- 1909705 TI - Serum bioactive and immunoreactive luteinizing hormone and follicle-stimulating hormone levels in women with cycle abnormalities, with or without polycystic ovarian disease. AB - Serum steroid, gonadotropin, and alpha-subunit levels were assessed in 35 women with cycle abnormalities [11 with and 24 without polycystic ovarian disease (PCOD) according to strict clinical and biochemical criteria] and 8 regularly cycling women in the early (cycle day 3 or 4) and mid (cycle day 7 or 8) follicular phase. LH and FSH levels were estimated using two immunological techniques [RIA and immunoradiometric assay (IRMA)] and in vitro bioassays (BIO), using mouse Leydig cells and rat granulosa cells, respectively. In PCOD patients mean alpha-subunit, free androgen index [FAI; testosterone x 100/sex hormone binding globulin (SHBG)], androstenedione, estrone, and estradiol (E2) were significantly elevated compared to levels in the early follicular phase of control cycles and non-PCOD patients. In addition, in PCOD patients mean IRMA-LH and RIA-LH levels were distinctly increased (2.8- to 3.6 fold, respectively; both comparisons, P less than 0.001) compared to control values, but in the same order of magnitude (1.3- to 1.4-fold increments) as that in non-PCOD patients. However, the median BIO-LH level in PCOD patients was 5.9-fold higher than that in non PCOD patients and 4.0-fold higher than the BIO-LH in the early follicular phase of control women. Consequently, the median BIO/IRMA-LH ratio was 4.8-fold higher in PCOD patients compared to non-PCOD patients. In women with cycle abnormalities, individual BIO/IRMA-LH ratios correlated with BIO-LH (rs = 0.48), FAI (rs = 0.39), free estrogens (E2/SHBG ratios; rs = 0 0.47), and dehydroepiandrosterone sulfate (rs = 0.60) concentrations. Mean IRMA-, RIA-, and BIO-FSH levels and BIO/IRMA-FSH ratios were not significantly different when various groups were compared. Although RIA- and IRMA-LH levels showed good correlation (rs = 0.88), RIA-LH levels were consistently higher, resulting in distinctly higher RIA-LH/FSH ratios (mean, 4.5) compared to IRMA-LH/FSH ratios (median, 1.8) in PCOD patients.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1909706 TI - Metabolic clearance of human follicle-stimulating hormone assessed by radioimmunoassay, immunoradiometric assay, and in vitro Sertoli cell bioassay. AB - We measured the equilibrium MCR of purified human FSH via continuous infusion and its half-life by bolus injection in gonadotropin-deficient men. Serum FSH concentrations were determined by RIA, immunoradiometric assay, and an in vitro FSH bioassay (rat Sertoli cell). At steady state, the MCR of FSH averaged 5.4 +/- 0.4 mL/min.m2, which was not statistically different in the three assays at the three different infusion rates. The half-life of FSH after bolus injection averaged 274 +/- 45 min (4.6 +/- 0.75 h) when analyzed as a single exponential, and 1.8 and 10 h for biexponential kinetics. The distribution volume of FSH was 3.1 L (immunoradiometric assay) and 2.1 L (bioassay). In summary, the MCR of human FSH is invariant across a range of physiological gonadotropin concentrations and quantitatively similar in three different immunological/biological assays. These results support the hypothesis that removal of circulating FSH molecules proceeds in parallel for immunoreactive and biologically active glycoprotein hormone. PMID- 1909707 TI - Pregnancy-induced changes in thyroid function: role of human chorionic gonadotropin as putative regulator of maternal thyroid. AB - Marked changes in maternal thyroid activity occur in pregnancy. It has been suggested that hCG may stimulate maternal T4 secretion, given its in vitro thyrotropic activity ascribed to a significant degree of structural homology with TSH. In a longitudinal study of 32 normal pregnant women, we attempted to clarify the functional activity of the thyroid in early and late pregnancy and the possibility of a nonpituitary control on the thyroid. Total T4 and T4-binding globulin levels were increased from the first trimester onward. Free T4 levels did not differ in the first trimester from postpartum values, but were significantly decreased in second and third trimesters (P less than 0.001). A decrease in TSH levels was observed in the first trimester (0.72 +/- 0.09 vs. 1.23 +/- 0.12 mU/L; P less than 0.001), while second and third trimester values did not differ from those postpartum. A significant negative correlation (P less than 0.05) was observed between hCG and TSH levels in the earliest weeks (8-10) of the first trimester. No correlation was found between hCG and total T4 or free T4 levels. A stimulation of I- uptake in FRTL-5 cells was induced by first trimester serum, which also showed a different behavior at chromatofocusing, with a higher proportion of hCG eluting at acidic pIs compared to second trimester samples. However, neither hCG levels nor the amount of acidic hCG correlated with the thyroid-stimulating activity measured in vitro. Some correlation was found with the percentage of basic hCG (eluting at pI greater than 4.6), although these isoforms were equally present in first and second trimesters. The differing patterns of circulating hCG at various stages of gestation suggest that distinct hCG isoforms may regulate maternal thyroid activity. PMID- 1909708 TI - The effect of long-acting analog of luteinizing hormone-releasing hormone on growth hormone secretory dynamics in children with precocious puberty. AB - Long-acting preparations of LHRH (LHRHa), such as leuprolide acetate, have been shown to selectively and reversibly suppress the clinical and biochemical features of central precocious puberty (CPP). The withdrawal of gonadal sex steroids results in a decline of growth velocity and a decrease in the rate of bone age maturation, with resultant improvement in predicted adult stature. The purpose of this study was to define GH secretory dynamics in children treated with leuprolide acetate. Twelve-hour nocturnal GH studies were performed in five children (four girls and one boy) with CPP before and after 6 months of treatment with leuprolide acetate. Mean GH levels, GH secretory rate, and number of GH secretory episodes were determined. Secretory profiles were analyzed using the Cluster program. Growth velocity, somatomedin-C, and dehydroepiandrosterone sulfate were measured before and after 6 months of therapy. By 6 months of therapy, there was a significant decrease in mean growth velocity from 10.5 +/- 3.3 to 6.7 +/- 1.6 cm/yr. Somatomedin-C levels remained the same at 46.90 +/- 9.51 and 52.5 +/- 12.40 nmol/L. Levels of dehydroepiandrosterone sulfate remained unchanged at 118.6 +/- 71.4 and 139.0 +/- 61.3 mumol/L at 0 and 6 months of the study. By 6 months, there was a significant decrease in mean GH levels from 13.6 +/- 5.3 to 6.4 +/- 3.4 micrograms/L (P less than 0.05). Total GH levels decreased from 1367.9 +/- 687.3 to 447.0 +/- 186.5 ng/12 h. The number of GH secretory episodes remained the same at 5.4 +/- 1.5 and 4.8 +/- 1.0/12 h at 0 and 6 months of study. Therefore, the decrease in GH that occurs during the withdrawal of gonadal sex steroids with LHRHa in children with CPP is an amplitude-modulated phenomenon, as the number of secretory peaks remains unchanged. PMID- 1909709 TI - Inhibition of human immunodeficiency virus gene amplification by heparin. AB - Gene amplification of virus-specific sequences is widely used as a method to detect or confirm human immunodeficiency virus (HIV) infection. In this study we used an enzyme-linked affinity assay to quantify polymerase chain reaction products from whole blood, plasma, and separated mononuclear cells collected in the presence of four common anticoagulants: acid citrate dextrose, sodium EDTA, potassium oxalate, and sodium heparin. Attenuation of the product signal was observed after amplification of nucleic acid extraction from whole blood, washed mononuclear cells, and plasma from specimens collected in sodium heparin. These inhibitory effects on gene amplification could be reversed with heparinase. The addition of as little as 0.05 U of heparin completely inhibited amplification of an HLA-DQa sequence from placental DNA. We conclude that heparin can cause attenuation or inhibition of gene amplification. Acid citrate dextrose and EDTA, which lack inhibitory activity, are the most appropriate anticoagulants for clinical blood samples when polymerase chain reaction amplification is anticipated. PMID- 1909710 TI - Use of a reamplification protocol improves sensitivity of detection of Mycobacterium tuberculosis in clinical samples by amplification of DNA. AB - We have compared the sensitivity and specificity of quantitative mycobacterial culture against results obtained by using the polymerase chain reaction for the detection of DNA from organisms of the Mycobacterium tuberculosis complex in 82 clinical specimens from patients suspected of having tuberculosis. Two amplification protocols were used, a standard amplification protocol, which amplifies a segment of the gene coding for the 65-kDa antigen, and a protocol in which the initial amplification products are reamplified with a second set of nested oligonucleotide primers. Although the standard amplification protocol gave positive results for 18 of 18 samples which grew greater than 100 CFU/ml and gave positive results in 4 of 35 specimens from patients with tuberculosis which were negative by culture, only 1 of 6 samples which grew less than 100 CFU/ml was positive. This lack of sensitivity could not be explained by the presence of inhibitors of Taq polymerase present in the original samples. In contrast, the reamplification protocol gave positive results for 24 of 24 samples which were positive by culture as well as for 13 of 35 samples from patients with tuberculosis which were negative by culture (overall sensitivity, 63%, P less than 0.02, compared with the standard amplification protocol and routine culture). Two of 23 samples from patients not diagnosed as having tuberculosis gave positive results when the standard amplification protocol was used, but no additional false-positive results were seen with the reamplification protocol (overall specificity, 91%). We conclude that the use of a reamplification protocol improves the sensitivity of detection of mycobacterial DNA in clinical samples without sacrificing specificity. The sensitivity of this approach appears to be superior to that of standard culture techniques. PMID- 1909711 TI - Francisella tularensis-induced in vitro gamma interferon, tumor necrosis factor alpha, and interleukin 2 responses appear within 2 weeks of tularemia vaccination in human beings. AB - Cell-mediated immunity is essential for protection against the intracellular bacterium Francisella tularensis, which causes tularemia. Positive in vitro T cell responses in the form of lymphocyte proliferation and lymphokine interleukin 2 (IL-2) and gamma interferon (IFN-gamma) secretion are found in memory immunity. Studies on the secretion of lymphokines with regard to the developing immunity to F. tularensis have not been published. Therefore, 14 subjects with no clinical history of tularemia were vaccinated with a live F. tularensis vaccine strain. The in vitro responses of five subjects (antigen-induced mononuclear cell and whole blood culture DNA synthesis and cytokine secretion) were measured twice a week throughout the period from 0 to 35 days after vaccination, and the peripheral blood lymphocyte subpopulations of nine subjects were determined between days 0 and 14. Positive reactions, i.e., responses exceeding those on day 0, were reached on day 10 with regard to the whole blood culture DNA synthesis response and IL-2 and IFN-gamma secretion and on day 14 with regard to the mononuclear cell DNA synthesis response and tumor necrosis factor alpha (TNF alpha) secretion. No measurable IL-4 was found in either the immune or nonimmune supernatants. Since the secretion of TNF-alpha was related to immunization, this points to the specificity of the phenomenon, even though the type of secreting cell is not yet known. If it is shown later that specific T cells produce it, the TNF-alpha response and the negative IL-4 finding may speak for the importance of the Th1-like pattern in immunity to F. tularensis. PMID- 1909712 TI - Immune reactivity to fractionated Leishmania aethiopica antigens during active human infection. AB - Fractionated antigen preparations of Leishmania aethiopica parasites were used to stimulate the peripheral blood lymphocytes of patients with active cutaneous leishmaniasis. In assays measuring lymphocyte proliferation, 9 of 10 patients with similar clinical presentations of infection responded in a similar pattern to the fractionated antigens. Marked proliferation was observed in response to antigen fractions with molecular masses of 43 to 36, 33 to 27, and less than 22 kDa. The induction of relatively high levels of gamma interferon (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) was also observed in responses to these same three antigen fractions. In contrast, the proliferative, IFN-gamma, and TNF alpha responses of patient lymphocytes to antigens with a molecular mass greater than 60 kDa were uniformly low. The results of this study suggest that the antigens of Leishmania parasites, which are recognized by T cells in patients with active cutaneous leishmaniasis, may be partitioned in the lower-molecular mass antigenic determinants associated with whole-parasite preparations. The observed association between antigen-induced proliferation and IFN-gamma and TNF alpha production may be indicative of potential disease-limiting immune effector activities which have developed during infection. PMID- 1909713 TI - Rapid method to extract DNA from Cryptococcus neoformans. AB - A rapid and easy method for the extraction of total cellular DNA from Cryptococcus neoformans is described. This procedure modifies and considerably simplifies previously reported methods. Numerous steps were either eliminated or replaced, including preincubations with cell wall permeability agents such as beta-mercaptoethanol and dithiothreitol. The commercially available enzyme preparation Novozyme 234 was found to contain a potent concentration of DNases which actively degrade DNA. Degradation and loss of DNA was prevented by maintaining a high concentration of EDTA in the lysing solution. This procedure resulted in high yields (150 to 200 micrograms of DNA from 100 ml of culture) of good-quality (undegraded), high-molecular-weight DNA which was readily digested by restriction endonucleases, making it suitable for use in various molecular applications. PMID- 1909714 TI - False resistance to imipenem with a microdilution susceptibility testing system. AB - Routine monitoring of antibiotic resistance at Children's Hospital, Boston, detected a dramatic increase in the prevalence of imipenem-resistant strains of Pseudomonas aeruginosa. Further studies documented that false resistance to imipenem was due, in part, to the loss of imipenem potency in customized MIC microdilution trays supplied by Sensititre Ltd. (West Sussex, United Kingdom). Recognition of the problem was delayed by use of the quality control standard recommended by the manufacturer, which were higher and broader than those suggested by the National Committee for Clinical Laboratory Standards. PMID- 1909715 TI - ACP Broadsheet 129: August 1991. Isolation and identification of Listeria monocytogenes. PMID- 1909716 TI - Comparison of assay systems for detecting antibodies to nuclear ribonucleoproteins. AB - The specificity and sensitivity of two commercial enzyme linked immunosorbent assays (ELISAs), Diamedix (Miami, Florida) and Lipogen (Noxville, Tennessee), were assessed and compared with haemagglutination and immunodiffusion assays. Sera from 53 patients with various connective tissue disorders were examined for the presence of antibodies to nuclear antigens (ANA), double stranded DNA (dsDNA), Sm, RNP, SSA/Ro, and SSB/La. Of the 53 patients, 42 were ANA positive, 11 were ANA negative, and 22 had antibodies to dsDNA. Seven patients had antibodies to Sm by haemagglutination assay; these were also positive in both ELISA systems (only five of the seven patients were assayed by the Lipogen ELISA system). Two additional Sm positive values were obtained in each of the ELISA systems but only one of these was positive in both. Ten positive RNP results were obtained by haemagglutination and nine of these were also positive by the Diamedix ELISA. Only eight samples were tested by the Lipogen assay and seven of these were positive. Three additional RNP positive values were obtained by the Diamedix and six by the Lipogen ELISA assays. Of these, only two were positive in both. Antibodies to SSA/Ro were obtained in 11 patients by immunodiffusion and lines of partial identity were observed in nine. SSB/La antibodies were positive in six patients and two had lines of partial identity. All the SSA/Ro and SSB/La positive sera were also positive in both ELISA systems. Moreover, eight additional SSA/Ro positive values were obtained in each of the ELISAs, four of which had partial identity lines in the immunodiffusion assay. Furthermore, three additional SSB/La positive values were obtained by the Diamedix and four by the Lipogen assays. Of these, only two were positive in both ELISAs. This study shows that the above ELISAs are comparable in specificity and sensitivity with haemagglutination assay for detection of antibodies to Sm and RNP antigens and are more sensitive than immunodiffusion for the detection of SSA/Ro and SSB/La antigens. PMID- 1909717 TI - Creating the leadership ethic. PMID- 1909718 TI - Teaching basic ethical concepts and decision-making: a staff development application. AB - Academic nursing programs are increasing the amount of ethical instruction presented to undergraduate and graduate students. However, nurses who graduated several years ago may find themselves without the background and skills needed to discuss the complex bioethical dilemmas they now face. This article presents the development of a continuing education program to acquaint nurses with basic ethical concepts and bioethical decision-making processes. Presentations were piloted with a small group of nurses from the outpatient department of a pediatric tertiary care hospital. PMID- 1909719 TI - The nursing shortage: the legal impact on documentation. AB - In 1985, two significant events occurred in the health care industry. These events ultimately proved to have a deleterious effect on the nursing profession. In an effort to contain spiraling health care costs, the federal government implemented a reimbursement system based on diagnosis related groups (DRGs). One of the major foci of this system was the length of stay, i.e., the shorter the stay, the greater the monetary profit for the institution. Therefore, patients were being admitted and discharged "sicker." These two events resulted in nurses being torn between the need for adequate documentation and the delivery of patient care. When one adds to this mix the legal environment in health care, with its focus on the adage "if it is not documented, it was not done," nurses were becoming increasingly frustrated and frightened. In light of current legal trends, this article reexamines this adage and discusses implications for the nurse educator. PMID- 1909720 TI - Learning needs assessment as a vehicle for integrating staff development into a professional practice model. AB - Restructured nursing roles resulting from innovative professional practice models and participative governance systems create a demand for new and expanded competencies. The impact for nursing staff development is the concurrent requirement to develop programs that match the skill/competency requirements of nurses in emerging practice models. This article recounts how one nursing department implemented a learning needs assessment (LNA) process as a means of integrating staff development into professional nursing practice. PMID- 1909721 TI - Nurses' knowledge of the code for nurses. AB - "Investigation of Professionalism in Nursing Behaviors" was funded by the Beta Upsilon Chapter of Sigma Theta Tau International and the College of Nursing, Arizona State University. Researchers asked 514 nurses in eight western states if they had a copy of the Code For Nurses. Most respondents did not have a copy of the Code; however, they indicated that adherence to the Code was essential to the professional nurse. Years of practice, educational background, participation in autonomous activities, and present position were variables used to determine those respondents most likely to possess a copy of the Code. Implications for continuing educators are discussed. PMID- 1909722 TI - Nursing and business: the new frontier. AB - Understanding free market principles is important for fulfilling nursing's obligation to professional stewardship. Stewardship is the act of conserving and enhancing what we have received from those before us, then disseminating it to new generations in the hopes of creating a stronger, more vital profession. In order to do that, nursing needs an improved understanding of the marketplace. This will help nursing grow as a profession, particularly through entrepreneurial and intrapreneurial efforts. PMID- 1909723 TI - Counseling hospitalized patients to quit smoking--study of an educational intervention. PMID- 1909724 TI - Certificate programs--an effective marketing strategy. PMID- 1909725 TI - Nurse readiness and time spent in self-directed learning. PMID- 1909726 TI - Organ referrals--would nurses do more if they knew more? PMID- 1909727 TI - Using visualization as a teaching technique. PMID- 1909728 TI - Circadian rhythm of serum immunoreactive inhibin in young and elderly men. AB - Serum testosterone (T) levels and inhibin levels decline with normal male aging. In addition, in young men, serum T levels demonstrate a circadian variation that is blunted or lost with normal aging. The purpose of this study was to determine whether serum immunoreactive inhibin levels also demonstrate a circadian variation in young men and if normal aging has an effect on the 24 hr serum inhibin pattern. Hourly blood samples were obtained for 24 hr from 7 young (age 25-35 yr) and 7 elderly (age 65-72 yr) healthy men. Serum inhibin and testosterone levels were measured by RIA. Similar to T, serum inhibin levels demonstrated a circadian pattern in young men. Elderly men also demonstrated a circadian rhythm in serum inhibin, with an average amplitude that was not significantly different from that found in young men, despite the fact that the average 24-hr inhibin level in the elderly men was significantly lower than in the young men. These results demonstrate that immunoreactive inhibin, like T, displays a circadian rhythm in the serum of adult men and the inhibin biorhythm is maintained in elderly men. PMID- 1909729 TI - In vitro characterization of a murine recipient anti-donor effector cell responsible for the development of chronic graft-versus-host disease. AB - Injection of parental spleen cells into unirradiated F1 hybrid recipients is frequently used for the induction of murine graft-vs-host disease (GVHD). Injection of C57BL/6 spleen cells into B6D2F1 recipients results in the acute form of GVHD whereas injection of DBA/2J cells into the same recipients results in a chronic form of GVHD. In vivo studies have suggested that injection of DBA/2J cells into B6D2F1 recipients results in the chronic form of GVHD instead of acute GVHD because of recipient B6D2F1 effector cells that inhibit DBA/2J CD8+ T cell function. The present report describes the development of an in vitro assay that measures the activity of these B6D2F1 effector cells. The results obtained using this assay indicate that these B6D2F1 effector cells are found primarily in the LN, need to be activated in order to function, are inhibited by anti-CD8 antibodies, and mediate their function as a result of DBA/2J cells binding to Ag expressed on their cell surface. PMID- 1909730 TI - Selective induction of high levels of IgA synthesis in Peyer's patch B cells by protein kinase C-activating phorbol esters. AB - To understand mechanisms of signal transduction involved in the regulation of isotype differentiation of B lymphocytes, we investigated effects of activation of protein kinase C (PKC) by phorbol esters and elevation of intracellular free calcium (Ca2+) by the calcium ionophore ionomycin (Ion) on Ig secretion by mouse Peyer's patch (PP) and spleen B cells. Results show that Ion suppressed production of IgM, IgG, and IgA by LPS-stimulated B cells whereas PKC-activating phorbol esters also inhibited LPS-induced IgM and IgG secretion, but induced a substantial IgA synthesis, as well as alpha-chain mRNA transcription, in B cells whether stimulated or not by LPS. Phorbol esters enhanced IgA response by directly activating PKC, inasmuch as the other phorbol ester, 4 alpha-phorbol 12,13-didecanoate, which is inactive with respect to PKC, had no effect on B cell differentiation. The increase in IgA secretion occurred in whole PP B cells, but not in the membrane IgA- B cell subset, suggesting that PKC activation does not promote the switching rate of IgM+ cells to IgA+ cells. Results from double staining studies of mIgA using FITC-labeled anti-IgA antibodies and DNA content using the DNA-binding propidium iodide showed that enhanced IgA response was not caused by IgA B cell clonal expansion. PMA induced low level of IL-6 production by highly purified PP B cells. However, addition of anti-mouse IL-6 antibody did not prevent PMA-enhanced IgA secretion, suggesting that IL-6 was not responsible for IgA induction by PMA. Collectively, the present data demonstrate that PKC activation and Ca2+ mobilization, which synergistically trigger cell proliferation, have differential effects on B cell isotype differentiation. Elevation of intracellular Ca2+ suppresses Ig production, but activation of PKC selectively enhances IgA secretion by directly promoting terminal differentiation of IgA-committed PP B cells into IgA-secreting plasma cells. PMID- 1909731 TI - Granulocyte-macrophage colony-stimulating factor is a major macrophage fusion factor present in conditioned medium of concanavalin A-stimulated spleen cell cultures. AB - In 1983, we reported that the conditioned medium (CM) of spleen cell cultures treated with Con A greatly induced fusion of mouse alveolar macrophages within 2 to 3 days at a very high rate of more than 80% (Proc. Natl. Acad. Sci. USA 80:5583, 1983). In the course of examining macrophage fusion factors (MFF) present in Con A-CM, we found that IL-4 induced fusion of alveolar macrophages with a time course similar to that induced by Con A-CM. However, the maximal fusion rate induced by IL-4 (4 ng/ml) was about 35%. Furthermore, the fusion induced by Con A-CM was blocked only partially by adding IL-4 antibody, indicating that there are unknown MFF other than in Con A-CM. Of several other cytokines produced by Con A-stimulated spleen cells, IL-6 (20 ng/ml), IFN-gamma (45 ng/ml) and granulocyte-macrophage (GM)-CSF (10 ng/ml) greatly potentiated the fusion induced by 4 ng/ml of IL-4. The assay of these cytokines in Con A-CM proved that it contained 0.44 +/- 0.04 ng/ml of IL-4, 1.0 +/- 0.24 ng/ml of IL-6, 9.1 +/- 0.07 ng/ml of IFN-gamma, and 11.6 +/- 1.66 ng/ml of GM-CSF. When the potentiating effects of IL-6, IFN-gamma and GM-CSF on macrophage fusion were examined in the presence of 0.4 ng/ml of IL-4, only GM-CSF increased the fusion rate to the maximal level induced by Con A-CM at its physiologic concentration (10 ng/ml). The macrophage fusion induced by Con A-CM was greatly suppressed by adding antibody against GM-CSF. GM-CSF had a biphasic effect on growth and fusion, depending on its dose levels used: 0.01 to 0.1 ng/ml increased proliferation without inducing fusion and 10 ng/ml preferentially induced fusion. There was a negative relationship between macrophage growth and fusion. IL-4 was a potent inhibitor of proliferation of macrophages induced by GM-CSF. These results clearly indicate that GM-CSF is a major MFF present in Con A-CM. PMID- 1909732 TI - IFN-gamma differentially modulates the susceptibility of L1210 and P815 tumor targets for macrophage-mediated cytotoxicity. Role of macrophage-target interaction coupled to nitric oxide generation, but independent of tumor necrosis factor production. AB - IFN-gamma primes murine macrophages to render them responsive for triggering by subactivating concentrations of bacterial LPS to mediate nonspecific tumor cytotoxicity. However, IFN-gamma also has direct anti-proliferative effects on transformed cells that serve as sensitive tumor targets for cytotoxic macrophages. We investigated the effects of preexposure of L1210 mouse leukemia and P815 mouse mastocytoma targets to rIFN-gamma on changes in their susceptibility to cytotoxicity by LPS-activated mouse peritoneal macrophages (PM). Co-incubation of inflammatory PM and either L1210 or P815 targets with IFN gamma and LPS produced a classical synergistic cytotoxicity for both targets over that of IFN-gamma or LPS alone. Similar synergistic augmentation of cytotoxicity occurred when effector PM were preprimed for 24 h with IFN-gamma before testing for cytotoxicity of untreated targets. However, pretreatment of L1210 and P815 targets for 24 h with IFN-gamma (50 U) before assay produced divergent results in that L1210 was more susceptible, whereas P815 was less susceptible to cytotoxicity by LPS-activated macrophages. Similar results were obtained when both macrophages and targets were pretreated separately with IFN-gamma for 24 h before their combined assay for tumor cytotoxicity. Pretreatment of L1210 targets for 1, 4, or 24 h with IFN-gamma produced similar effects on their increased susceptibility to macrophage cytotoxicity. In contrast, P815 pretreated for 1 and 4 h with IFN-gamma showed an early increased susceptibility to macrophage cytotoxicity followed by a decrease after 24 h pretreatment. The pretreatment of L1210 or P815 targets with IFN-gamma before their exposure to LPS-activated macrophages had no effect on the production of TNF. However, there was a corresponding increase in nitric oxide generation by LPS-activated macrophages after their exposure to IFN-gamma pretreated L1210 targets and a decrease in the presence of IFN-gamma-pretreated P815 targets that correlated with their changes in susceptibility to macrophage killing. Nitric oxide generation by macrophages alone in response to LPS was found to be greater than when effector macrophages were exposed to the tumor targets and this was either increased by L1210 or decreased by P815 that had been pretreated with IFN-gamma. Our results indicate that IFN-gamma may act directly and differentially on tumor targets to alter their susceptibility for macrophage cytotoxicity, which was coupled to changes in the generation of cytotoxic nitric oxide, rather than TNF production by the macrophage.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1909733 TI - Human IgA and IgG F(ab')2 that bind to staphylococcal protein A belong to the VHIII subgroup. AB - Staphylococcal protein A (SPA) is a bacterial membrane protein that possesses, in addition to its Fc gamma-binding activity, a distinct specificity for the Fab region of some IgM, IgA, IgG, and IgE. The Fab site that binds to SPA has been localized to the V region of the Ig H chain. In a previous study of human monoclonal and polyclonal IgM, we demonstrated that binding to SPA was highly restricted to molecules of the VHIII subgroup, and that nearly all VHIII IgM were able to bind SPA. The present study examines the VH composition of SPA-binding and SPA-nonbinding fractions of purified human polyclonal IgA, and IgG F(ab')2 fragments. We found that 22% of the IgA and 15% of the IgG F(ab')2 bound to SPA agarose. Analysis with VH subgroup-specific antisera indicated that the SPA binding fraction of IgA was dominated by the VHIII subgroup, and the SPA-binding fraction of IgG F(ab')2 contained only VHIII molecules. Furthermore, substantial portions of the total VHIII protein in IgA and in IgG F(ab')2 bound to SPA. We conclude that Fab binding to SPA is both restricted to and highly prevalent among human VHIII molecules, regardless of Ig class. These results suggest that protein A is an Ig superantigen. PMID- 1909734 TI - Mechanisms of granule enzyme secretion from permeabilized guinea pig eosinophils. Dependence on Ca2+ and guanine nucleotides. AB - The mechanisms of granule protein secretion have been studied in streptolysin-O permeabilized guinea pig eosinophils. Secretion of the granule-associated enzyme N-acetyl-beta-D-glucosaminidase was dependent on both Ca2+ and a nonhydrolyzable GTP analogue, guanosine-5'-O-(3-thiotriphosphate) (GTP-gamma-S), suggesting roles for both calcium and GTP binding proteins. Secretion was maximal by 7 min, and varied between 35 and 60% of the total enzyme activity. Other GTP analogues also elicited secretion, with rank order GTP-gamma-S greater than guanylyl imidophosphate greater than guanylyl (beta-gamma-methylene-diphosphate). Unrelated nucleotide triphosphates showed little or no effect confirming the specificity of the G protein. Transmission electronmicroscopy confirmed that permeabilization alone did not result in loss of granules and that exocytosis was dependent on the addition of the effectors, Ca2+ and GTP-gamma-S. ATP enhanced the magnitude of the secretory response and also enhanced the effective affinities for both Ca2+ and GTP-gamma-S. In the presence of 10(-5) M GTP-gamma-S the ED50 (Ca2+) was pCa 5.57 +/- 0.04 (2.69 microM) in the absence of ATP and declined to pCa 6.16 +/- 0.03 (0.69 microM) in the presence of ATP (p less than 0.0001). Furthermore, ATP served to restore responsiveness in cells that had been rendered refractory by delaying stimulation after permeabilization. Pretreatment with PMA (an activator of PKC) inhibited the induction of a refractory state, whereas inhibition of PKC partially countered the ability of ATP to restore responsiveness, both observations pointing to a requirement for a specific component of the secretory mechanism to be in a phosphorylated state in order to condone the secretion process. These observations show that secretory mechanisms in eosinophils are similar to those in other myeloid cells, in particular neutrophils and mast cells, although the time course of secretion is more protracted. PMID- 1909735 TI - Immunosuppression induced by attenuated Salmonella. Reversal by IL-4. AB - We previously demonstrated that an aroA- strain of Salmonella typhimurium, which provides excellent protection against virulent Salmonella challenge, also rendered immunized mice unable to mount in vivo and in vitro antibody responses to heterologous Ag. Coculture studies using transwell plates indicated that suppression was mediated by soluble factors. The suppressive cells were identified as belonging to the monocytic linkage. Macrophage precursors as well as mature adherent macrophages mediated the observed suppression. In the present study, the mechanism of immunosuppression was investigated. Suppression was found to be genetically nonrestricted as spleen cells from immunized C3HeB/FeJ mice (H 2k) suppressed the anti-SRBC plaque-forming cell (PFC) responses of normal spleen cells from two MHC noncompatible mouse strains, BALB/c (H-2d) and C57BL/6 (H-2b). Time course experiments demonstrated that the addition of spleen cells from immunized mice to normal splenocytes as late as day 4 of a 5-day assay was still markedly suppressive. Furthermore, suppression of the PFC responses was accompanied by a profound inhibition of the capacity of immune splenocytes to produce IL-2 in response to in vitro stimulation by Con A. Coculture studies showed that immune spleen cells were able to suppress IL-2 production by normal splenocytes in a dose-dependent fashion. However, the suppressed PFC responses of immune spleen cells could not be reversed by the exogenous addition of up to 200 U/ml of IL-2, suggesting that immune splenocytes are also defective in their ability to respond to IL-2. In marked contrast, suppression of PFC responses was reduced by more than 50% by the addition of as little as 1 U/ml of IL-4 and was completely abrogated when 5 U/ml of IL-4 were added to in vitro cultures of spleen cells from immunized mice. The antisuppressive action of IL-4 appeared to be via its inhibitory effect on activated macrophages. The implications of the above findings are discussed. PMID- 1909736 TI - Human IgA1 blockade of IgG-initiated lysis of Neisseria meningitidis is a function of antigen-binding fragment binding to the polysaccharide capsule. AB - We have recently shown that human IgA1 can initiate lysis of group C Neisseria meningitidis via the classical C pathway when bound to specific outer membrane proteins, but that IgA1 can also function as a blocking antibody when bound to the polysaccharide capsule of meningococci. In this report, we further characterized IgA1 blockade by examining the effect of IgA1 on IgG-initiated immune lysis of group C meningococci. We purified IgG and monomeric IgA1 from either convalescent group C meningococcal case sera or tetravalent (A, C, Y, W135) polysaccharide vaccinate sera. In the absence of IgA1, IgG initiated complete lysis (greater than 99%) of strains 118V (C:P3,4:L2,4) 126E (C:P3:L1,8), and 35E (C:P5:L2). Addition of IgA1 to the bactericidal reaction mixture completely blocked the lytic function of IgG. Removal of the Fc portion of IgA1 with either pepsin or IgA1 protease did not affect blockade. Both the F(ab')2 and Fab derivatives of IgA1 blocked lysis quantitatively as well as intact IgA1. The Fc fragment produced by IgA1 protease cleavage neither increased nor decreased Fab-mediated blockade. IgA1 and its Fab and F(ab')2 fragments blocked IgG initiated lysis via either the classical pathway in factor B-depleted and in properdin-deficient serum, the alternative pathway in MgEGTA-chelated serum, or both pathways combined. Absorption of the IgA1 and IgG with alum-bound group C polysaccharide completely removed blocking and lytic activity, respectively, indicating that both the blocking IgA1 and the lytic IgG were specific for the group C capsule. Blocking by IgA1 was a linear function of the polysaccharide Ag binding capacity (ABC) ratio of blocking IgA1 to lytic IgG. Complete blockade was observed at an ABC ratio of 5.5. At ABC ratios of 3.3 and 4.4, IgA1 affected significant blockade whether added previous to, concurrent with, or subsequent to sensitization of the organisms with IgG. With the use of a C polysaccharide ELISA, we found that the binding of IgA1 to the group C capsule in the presence of IgG exhibited positive cooperativity and therefore that blockade was independent of the ability of IgA1 to directly compete with IgG for binding to epitopes within the group C capsule. We conclude that IgA1, when bound to the group C polysaccharide capsule, can block IgG-initiated lysis of group C meningococci through either the classical or the alternative pathway before or after the organism is exposed to IgG, and that blockade is an Fc-independent event. PMID- 1909737 TI - Human recombinant migration inhibitory factor activates human macrophages to kill Leishmania donovani. AB - A recombinant form of the first lymphokine to be discovered, migration inhibitory factor (rMIF) was obtained from COS-1 cells transfected with a cDNA library from a human T cell hybridoma (6). rMIF has an amino acid sequence unrelated to that of any known protein. To learn more about the biology of MIF, we tested its ability to effect the survival of Leishmania donovani in macrophages. We found that rMIF activates blood monocyte-derived macrophages in vitro to suppress the growth of and kill these intracellular parasites. The anti-leishmanial effect (ranging from 50 to 77% reduction of parasites) is maximal when macrophages have been incubated with rMIF 48 to 72 h before infection and is similar to that seen with macrophages activated by IFN-gamma. Of interest, whereas the activation of human macrophages by IFN-gamma is inhibited by IL-4 and not enhanced by LPS, the activation by rMIF is enhanced by LPS but is not inhibited by IL-4. The data presented here demonstrate that rMIF is a potent activator of macrophages and is likely to be critical in cell-mediated immune host defenses. PMID- 1909738 TI - Human endothelial cells are activated by IFN-gamma to inhibit Toxoplasma gondii replication. Inhibition is due to a different mechanism from that existing in mouse macrophages and human fibroblasts. AB - Toxoplasma gondii invaded and proliferated in cultured human umbilical vein endothelial cells. Preincubation of the human umbilical vein endothelial cells with human rIFN-gamma induced a high degree of inhibition of T. gondii replication, with the effect being dose dependent. In order to try to elucidate the inhibitory mechanism, we tested the presence of several factors that are known to operate against intracellular parasites in other cell types. We found, by means of a competitive inhibitor, that L-arginine-dependent production of reactive nitrogen intermediates was not the cause of inhibition of T. gondii proliferation, thus contrasting with the inhibitory mechanism found in activated mouse macrophages. Furthermore, the inhibition of replication was not overcome by oxygen scavengers or by saturation of the system with tryptophan, suggesting that neither reactive oxygen intermediates nor the induction of tryptophan starvation was responsible. PMID- 1909739 TI - Influence of a V kappa 8 L chain transgene on endogenous rearrangements and the immune response to the HA(Sb) determinant on influenza virus. AB - A rearranged murine V kappa 8/J kappa 5 L chain gene that codes for the L chain of most antibodies generated in the primary response of BALB/c mice to the antigenic site, Sb, of the hemagglutinin (HA) molecule of influenza virus A/PR/8/34 (PR8) has been cloned. Three transgenic lines were generated by microinjecting the gene. Lines Ga and L each contain a single copy of the transgene whereas line Gb contains three complete copies. Mice of the Ga lineage showed increased V kappa 8-specific mRNA levels only in spleen, but not in nonlymphoid organs and therefore displayed apparently normal lymphoid-specific regulation of the Ig transgene. B cell hybridomas generated from these mice were analyzed for rearrangements of endogenous V kappa genes. Greater than 90% of the C kappa alleles were retained in germ-line configuration in the Ga line, compared with only 0 to 18% in the L line. Thus, a wide variation in the frequency of endogenous rearrangements is seen among mice of different lineages using the same transgene construct. None of more than 150 hybridomas derived from LPS-stimulated splenic B cells of Ga mice exhibited HA-binding activity although they expressed the transgene and, in most cases, excluded endogenous V kappa rearrangements. In contrast, a large fraction of hybridomas isolated after primary immunization with PR8 were HA(Sb)-specific. This indicated that the transgene was functional but formed HA-specific antibodies with a more restricted set of H chains than previously hypothesized. The primary anti-HA response to immunization with PR8 was diminished in all lines compared with normal mice except for a slightly accelerated but transient burst of anti-HA antibody formation in two out of three lines (Ga and Gb). This early response in G lineage mice was largely specific for HA(Sb) and thus appeared to be composed of transgene-expressing antibodies. No differences in serum titers were observed in the secondary anti-HA responses to booster inoculation with PR8 between transgenic and normal mice. PMID- 1909740 TI - Tumor necrosis factor-alpha mRNA accumulation in human myelomonocytic cell lines. Role of transcriptional regulation by DNA sequence motifs and mRNA stabilization. AB - The cytokine TNF mediates many of the pathologic signs of cachexia, inflammation, and sepsis. The current work describes the regulation of TNF in human myelomonocytic cell lines after PMA stimulation. The cell lines exhibit a low level of constitutive TNF mRNA expression. Within 2 to 4 h of PMA exposure, steady state levels of TNF mRNA are markedly elevated in all myelomonocytic cell lines studied. This rise is due to increased mRNA stability, which increased by almost twofold, and to an overall increase in transcription, which rises by more than sixfold. At the level of the genomic TNF gene, a DNase I hypersensitive site is detected within the TNF promoter between -200 to -100 bp relative to the transcription initiation site. Although absent in nonexpressing erythroleukemia cell lines, the DNase I site is present in uninduced myelomonocytic cell lines and is not changed after PMA induction. The PMA induction of c-fos mRNA correlated well with TNF gene induction; expression of genes encoding other proteins in the AP-1 complex (junB and junD) were also induced by PMA. The nuclear extracts from resting and induced ML-1 cells contain proteins binding specifically to the AP-1, AP-2, and NF kappa B sequence located within the TNF promoter. PMA induction increases the level of a number of specific binding complexes relative to the resting cells. The regulatory mechanisms of the human and murine TNF genes are discussed. PMID- 1909742 TI - [G protein--regulation of K channel]. PMID- 1909741 TI - [Mitogenic signaling pathways of growth factors can be distinguished by the involvement of pertussis toxin-sensitive GTP-binding protein and of protein kinase C]. PMID- 1909743 TI - [Effects of gonadotropin and estrogen on endogenous growth factor synthesis in the porcine theca]. AB - In order to investigate the effects of FSH, LH and estradiol (E2) on the synthesis of endogenous growth factor from the thecal tissue, porcine thecal tissues obtained from follicles (greater than 3mm) were cultured for 24 hours in serum-free media in the presence of various concentrations of FSH, LH and E2. After the incubation, thecal tissues and thecal conditioned media (CM) were collected. The growth-promoting activity of thecal CM and thecal cytosol of each conditioned group was assayed by measuring 3H-DNA synthesis in mouse BALB/c 3T3 cells. E2 increased the growth-promoting activity of thecal CM significantly in comparison with controls, whereas neither FSH nor LH showed any significant effects. However, the growth promoting activity in the cytosols was almost the same in all conditioned groups. These results indicate that E2 stimulates the synthesis and secretion of thecal growth factor without changing the original properties. PMID- 1909744 TI - Contraception. PMID- 1909745 TI - Behavioral thermoregulation of the toad, Bufo marinus: effects of air humidity. AB - Two experiments were performed. The first tested the hypothesis that the toad, Bufo marinus, will select a lower ambient temperature under dry environmental conditions. This behavioral response would reduce evaporative water loss and facilitate survival on land. The second experiment measured the effects of temperature on evaporative water loss. In the first experiment, toads were placed in a thermal gradient (11-40 degrees C) for 3 days. On days 1 and 3, water-filled dishes were placed along the temperature gradient and humid air was circulated through the chamber. On day 2, water dishes were removed, and dry air was circulated through the chamber. Body temperature (Tb) was recorded with a cloacal thermistor. Selected Tb was approximately 8.6 degrees C lower during the dry conditions than during the humid conditions. The behavioral hypothermia took about 6 h to develop. In the second experiment, a reduction in Tb from 17.7 to 12 degrees C reduced evaporative water loss by 42%. Consequently, behavioral hypothermia of the toad is an important adaptation to dry environmental conditions. PMID- 1909746 TI - Distinctions in growth cone morphology and motility between monopolar and multipolar neurons in Drosophila CNS cultures. AB - Growth cones play a central role in determining neurite extension, pathfinding and branching, and in establishing synaptic connections. This paper describes an initial characterization of growth cone morphology and behavior in dissociated larval central nervous system (CNS) cultures of Drosophila. Contrast-enhanced video images of growth cones in monopolar and multipolar neurons were characterized by employing morphometric parameters such as the number and length of filopodia, and the area and roundness of the lamellipodia. Behavior of growth cones was analyzed by a motility index and boundary flow plots originally devised for measuring motility in other cellular systems. We found that separate CNS regions yielded cultures of different major cell types with distinct neuritic patterns that could be correlated with the morphology and motility of the associated growth cones. Monopolar neurons were the major cell type in brain cultures, whereas multipolar neurons were predominant in ventral ganglion cultures. Moreover, the growth cones of monopolar neurons, which are likely to be associated with the axonal processes, differed from those of multipolar neurons, which might be related to dendritic terminals. Growth cones in monopolar neurons had larger lamellipodia of less erratic shape accompanied by fewer and shorter filopodia, and, when active, displayed much higher motility and less directionality in motion. Alternatively, these morphological and behavioral distinctions between monopolar and multipolar neurons may result from intrinsic differences in membrane adhesion and intracellular transport properties. PMID- 1909747 TI - Location and connectivity of abdominal motoneurons in the embryo and larva of Drosophila melanogaster. AB - The soma location and peripheral connectivity of motoneurons in abdominal segments of the embryo and larva of the fruitfly, Drosophila melanogaster are described as an initial step in determining the mechanisms by which motoneurons make connections with their target muscles in a genetically accessible organism. Embryonic motoneuron somata were retrogradely labelled by application of the fluorescent dye, DiI, to the whole peripheral nerve or to its separate anterior or posterior fascicles in segments A5-A7 of late stage 15/early stage 16 embryos. This technique reveals a stereotyped, segmentally repeated population of 34 motoneurons per hemisegment, several of which can be individually identified from their soma position. The same set of motoneurons was revealed in third instar larvae of D. melanogaster by cobalt backfilling of abdominal peripheral nerves, although the positions of some of these neurons change during larval development. The peripheral connectivity and axon morphology of several of the abdominal motoneurons was determined by intracellular injection with Lucifer Yellow in stage 16 embryos. For the motoneurons with axons in the anterior fascicle there is no clear relationship between somata groupings and the muscle targets innervated: contrary to earlier claims, these motoneurons arborize over both ventral and dorsal muscles. Individual motoneurons possess a stereotyped pattern of terminal arborization. PMID- 1909748 TI - A summary index for the assessment of quality of life in angina pectoris. AB - When exploring the effects of anti-anginal therapy on quality of life (QL), it is essential to use concise, reliable, outcome measures which focus on those aspects of the disease which are affected by the anginal pain, and which are expected to be responsive to medical intervention. Analysis based on a single comprehensive index is preferable to the use of several indexes as it avoids the potential for conflicting inferences from multiple comparisons. In this paper, we describe the development of a QL index which summarizes the three questionnaires used in the North Karelian Quality of Life (KarQuol) study. The summary index (SI) will be used to compare transdermal and oral nitrate therapy in patients with angina pectoris, and represents the first stage in the construction of a disease specific evaluative index for future trials. PMID- 1909749 TI - Anti-anginal therapy and quality of life. A comparison of the effects of transdermal nitroglycerin and long-acting oral nitrates. AB - A total of 112 male patients with severe effort-induced angina pectoris (New York Heart Association functional classes II and III) participated in a randomized open trial consisting of a 6 month phase with 3 month treatment cross-overs. The aim of the study was to compare the effect of transdermal nitroglycerin (TN) patches and long-acting oral nitrates (LAON) on quality of life (QL). During the cross-over period 30 patients (20 on TN and 10 on LAON) withdrew from the study, over half of them within the first month. Although the results should be interpreted with some caution, they showed that improvement in QL was present for both treatments but greater during the transdermal therapy (unadjusted p = 0.07, adjusted p = 0.03). Anginal attacks were associated with improved QL scores, and fewer attacks occurred on TN (p = 0.06). Improvement in QL was most pronounced in patients whose recorded duration of angina was less than 8 years. PMID- 1909750 TI - Capnometry for continuous postoperative monitoring of nonintubated, spontaneously breathing patients. AB - We continuously monitored spontaneous respiration after extubation by end-tidal CO2 tension (PETCO2) in 19 patients aged 20 to 72 years who had undergone major operations. The respiratory gas was sampled from the nasopharynx via a special nasal catheter and analyzed by a side-stream analyzer. In each case, optimal placement of the nasal catheter was determined by CO2 waveform and the capnograms were recorded for waveform analysis and trend monitoring. PETCO2 was compared with arterial CO2 tension (PaCO2) two to four times during the 2- to 19-hour observation periods by simultaneous measurements. For 65 simultaneous measurements, mean PETCO2 was 38.9 +/- 5.7 mm Hg (range, 26.3 to 48.3 mm Hg) and mean PaCO2 was 38.9 +/- 5.7 mm Hg (range, 26.8 to 46.0 mm Hg; r = 0.82; p less than 0.01). While the mean values for PETCO2 and PaCO2 were similar, several patients had large differences for PaCO2 to PETCO2. The differences of the individual patients did not differ significantly between the various times of measurement. We conclude that this form of capnometry is well suited for continuous, noninvasive monitoring of respiration in nonintubated, spontaneously breathing patients. PMID- 1909751 TI - An improved nasal prong apparatus for end-tidal carbon dioxide monitoring in awake, sedated patients. AB - We describe and evaluate a new apparatus that monitors end-tidal carbon dioxide (PETCO2) and augments the inspired oxygen concentration in awake, sedated patients. The unit was evaluated for its effectiveness as an oxygenation device and its accuracy as a predictor of PaCO2 through the correlation of PaCO2 with PETCO2. Twenty cardiac surgical patients, physical status ASA 2-4, participated in this study. The PETCO2 monitoring device consisted of a dual-prong nasal oxygen cannula and a 14-gauge intravenous catheter that was inserted into one limb of the oxygen supply tubing and connected to a Datex gas analyzer (Datex Instrumentation Corp, Helsinki, Finland) to measure PETCO2. The cross-over passage between the prongs was intentionally blocked with the end of a wooden core cotton swab. The oxygen flow rates were randomly varied (2, 4, and 6 L/min) every 5 minutes, and values for PETCO2 as well as arterial blood samples for analysis of PaCO2 and PaO2 were obtained at the end of each 5-minute period. The accuracy of the system was assessed by comparing the PaCO2-PETCO2 differences (bias) at each oxygen flow rate. The ratios of PETCO2 compared with PaCO2 were 0.98, 0.94, and 0.85, with correlation coefficients of r = 0.81, 0.85, and 0.63, respectively. The PaO2 values were 114, 154, and 183 mm Hg for the corresponding nasal oxygen flow rates of 2, 4, and 6 L/min, respectively. This study indicates that this modified nasal cannula provides supplemental oxygen adequately and yields a satisfactory reflection of the PaCO2 depending on the oxygen flow rate delivered. PMID- 1909752 TI - Sensitivity of a disposable end-tidal carbon dioxide detector. AB - A small disposable carbon dioxide detector that can be used to provide evidence of correct endotracheal tube placement is now commercially available (FEF). The device contains an indicator that changes color when exposed to carbon dioxide. This study measured the lowest concentration of carbon dioxide causing a perceivable color change in the device. Ten volunteers were blinded to the concentrations of carbon dioxide in an airway circuit/lung model, and the minimal concentration of carbon dioxide that caused a perceivable color change was recorded. The mean minimum concentration required for detection of a color change was 0.54% (4.1 mm Hg) and ranged from 0.25 to 0.60% (1.9 to 4.6 mm Hg). We conclude that this device should produce a detectable color change even in patients with low end-tidal carbon dioxide, as might be observed during cardiopulmonary resuscitation. PMID- 1909753 TI - Efficacy of hepatitis B screening in a private obstetrical population. AB - We sought to determine whether the recent Centers for Disease Control recommendation of universal prenatal screening for hepatitis B surface antigen (HBsAg) is necessary or cost-effective in a population of private patients. During the 21 months of our study there were 17,973 deliveries at Magee-Womens Hospital, the largest-volume private obstetrics service in the United States. We screened 12,377 of these patients for HBsAg. Only 11 patients, 0.09% of those screened (5 private and 6 clinic) tested positive. We administered questionnaires regarding historical risk factors for hepatitis B to all 11 patients testing positive for HBsAg and to 100 controls who tested negative for HBsAg. All private patients and 5 of 6 clinic patients testing positive for HBsAg had identifiable risk factors for hepatitis B. In addition, historical risk factors for hepatitis B were identified in 29% of the women testing negative for HBsAg. We found historical risk factors to be excellent predictors of the presence of HBsAg in our private patients. Our data indicate that universal screening for HBsAg is not necessary in private patients. PMID- 1909754 TI - Enzyme-linked immunosorbent assay to detect Mycobacterium tuberculosis antigen 5 and antimycobacterial antibody in cerebrospinal fluid of patients with tuberculous meningitis. AB - Inhibition ELISA and indirect ELISA was standardised to detect Mycobacterium tuberculosis antigen 5 and antimycobacterial antibody in cerebrospinal fluid (CSF) specimens of 75 patients with tuberculous meningitis, (TBM) and 75 patients with non-tuberculous neurological diseases (control group). In both ELISAs, no false-negative results were observed in 15 culture proven patients with TBM. Detection of M. tuberculosis antigen 5 is more sensitive than detection of antimycobacterial antibody. However, both ELISAs showed 100% specificity for tuberculous aetiology in culture-negative patients with TBM. ELISA should be considered as one of the approaches in the laboratory diagnosis of TBM, particularly when standard bacteriological methods are unable to demonstrate M. tuberculosis in CSF specimens of patients with TBM. PMID- 1909755 TI - Limbal xanthogranuloma. AB - Three cases of histologically proven limbal xanthogranuloma are presented. All three cases presented with a yellow raised swelling at the limbus and no other ocular or systemic abnormality. A simple excision of the lesion was carried out in all cases and histological examination revealed features typical of xanthogranuloma. Two patients had a recurrence at the original site, necessitating keratectomy, with insertion of a lamellar graft. We suggest that a primary keratectomy with insertion of a lamellar graft should be performed in cases of limbal xanthogranuloma in order to lessen the risk of recurrence and to provide a better cosmetic result. PMID- 1909756 TI - Overview of the HCFA study of cost and utilization of AIDS services in California and New York. PMID- 1909757 TI - Nitrate tolerance: effect of thiol supplementation during prolonged nitroglycerin infusion in an in vivo rat model. AB - Depletion of intracellular sulfhydryl groups has been considered a main reason for the development of nitrate tolerance during sustained nitrate therapy. Although administration of N-acetyl-cysteine, a sulfhydryl donor, potentiates the acute hypotensive effect of nitroglycerin (NTG), its role in the reversal of nitrate tolerance is controversial. In the present study, we developed a conscious in vivo rat model to study nitrate tolerance and nitrate-thiol interactions. Tolerance to NTG, as assessed by the blood pressure reduction in response to i.v. NTG bolus doses, developed after 24 h of i.v. NTG infusion. After 3 and 5 days of 0.2 mg/h NTG i.v., the dose-response relations for NTG induced reduction in blood pressure were shifted to 25-fold higher doses (P less than .01). Infusion of N-acetylcysteine (0.245, 1.225 and 6.125 mmol/kg/h for 4 h) and, to a lesser extent, equimolar doses of reduced glutathione, but not N acetylserine, significantly potentiated the hypotensive effect of NTG, in a dose dependent manner (P less than .05). However, complete reversal of tolerance was not achieved. This animal model of nitrate tolerance is suitable for further investigations of nitrate-thiol interactions and shares similarities with nitrate tolerance development in humans. The results suggest that sulfhydryl supplementation may enhance the hypotensive effect of NTG in a dose-dependent manner. This effect is more likely to be achieved with N-acetylcysteine than with glutathione and may be related to differences in membrane permeability. PMID- 1909759 TI - Postnatal development of lamb intestinal digestive enzymes is not regulated by diet. AB - 1. Change in digestive enzyme activities determined biochemically in brush-border membrane vesicles and cytochemically in isolated villi of lamb proximal intestine has been related to diet, intestinal structure and rumen development during the first 10 weeks of postnatal life. 2. Lactase activity halved, dipeptidylpeptidase IV activity doubled and aminopeptidase N and alkaline phosphatase activities remained constant during this period of development. Maintaining lambs on a milk replacer diet for 5 weeks after birth had no effect on this pattern of postnatal change in digestive enzyme activities. 3. Structural changes accompanying these selective effects on enzyme expression included a halving of villus height and a doubling of villus width. Villus surface area remained unaffected by these changes in height and width of villi. Crypt depth doubled during the first 10 weeks of postnatal life. Maintaining lambs on a milk replacer diet for 5 weeks did not affect this pattern of change in intestinal structure. 4. It appears from these results that postnatal decrease in lactase and increase in dipeptidylpeptidase IV activities are not regulated by factors such as diet, rumen development, or changes in intestinal structure. Attention is drawn to differences encountered between these results and a postnatal modification of glucose transport which clearly is dependent on diet. PMID- 1909758 TI - Physiological characterization of two functional states in subpopulations of prolactin cells from lactating rats. AB - 1. Lactotroph cells from lactating female rat pituitary glands were dissociated, separated and enriched on a continuous gradient of bovine serum albumin at unit gravity. Two lactotroph subpopulations were observed in the light (F(3-5)) and the heavy (F(7-9)) fractions of the gradient. Both populations were maintained for at least 6 days in culture before experiments were performed. 2. Patch-clamp recordings, in the whole-cell mode, were performed on both lactotroph subpopulations in order to measure passive membrane properties and Ca2+ currents. Resting membrane potential as well as membrane capacitance values were found to be lower in light fraction cells. The two components of Ca2+ currents, called fast and slow deactivating (FD and SD) currents, were present with different proportions in each subpopulation; the ratio of current amplitudes, SD/FD, was 2.42 +/- 0.41 (n = 18) in light fraction cells and 1.17 +/- 0.27 (n = 17) in heavy fraction cells (P less than 0.02). 3. Reverse haemolytic plaque assay showed that in the light and heavy fractions, 68 and 47% of the lactotroph cells, respectively, were secreting. Population analysis of the plaque areas revealed a bimodal frequency distribution of plaque sizes consisting of small (1500 microns 2) and large plaques (3995 microns 2). A majority of light fraction cells produced large plaques whereas most of the heavy fraction cells produced small plaques. 4. Perifusion experiments performed on enriched prolactin cells showed that (1) basal prolactin (PRL) release was higher in light fraction than in heavy fraction cells, (2) the dopamine (10(-8)M)-induced inhibition of PRL release was greater in light fraction cells (86 +/- 15%) than in heavy fraction cells (41 +/- 21%), and (3) the thyrotrophin-releasing hormone (TRH, 10(-8)M)-induced increase of PRL release was 150 +/- 60% in light fraction versus 330 +/- 82% in heavy fraction cells. 5. Current-clamp recordings were performed using the intracellular technique. Lactotrophs were categorized according to their electrophysiological response following application of dopamine or TRH (both 10( 8)M). In the light fractions, the majority of the cells tested were hyperpolarized by dopamine (68%), whereas only 7% were depolarized by TRH application. In the heavy fractions, most of the cells (63%) responded to TRH application, while only 13% were dopamine sensitive. 6. Cytosolic free Ca2+ concentration ([Ca2+]i) measurements with the fluorescent probe Indo-1 revealed two lactotroph subtypes. Most cells in the light fractions (sixteen of twenty-two tested cells) exhibited an unstable level of [Ca2+]i with values fluctuating between 114.1 +/- 34.3 and 221 +/- 50 nM (mean +/- S.D.). Application of dopamine or of the D2 receptor agonist RU 24213 (10(-8)M) resulted in the disappearance of these fluctuations and in an accompanying decrease in basal [Ca2+]i level.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1909760 TI - A comparison of human recombinant tissue-type plasminogen activator and urokinase in microsurgical thrombolysis in the rat. AB - A comparison was made between several characteristics of tissue-type plasminogen activator (t-PA) and urokinase (UK), potentially useful in microsurgery to restore perfusion to ischemic free-tissue transfers. An intraarterial infusion of one of the drugs (or normal saline [NS] as a control) was performed in conjunction with a rat femoral vein clot model. Both t-PA and urokinase were effective in lysing 100 percent of the venous clots on the side of infusion. This occurred in only 25 percent of controls (p = .0035). Thrombolysis on the contralateral side, a measure of systemic effect, occurred in 38 percent, 50 percent, and 13 percent of veins using t-PA, UK, and NS, respectively (t-PA vs. UK p = 1.0, t-PA vs. NS p = .28, UK vs. NS p = .14). Rethrombosis occurred in 13 percent and 25 percent of ipsilateral veins treated with t-PA and urokinase, respectively, and in one of the two veins that had resumed flow during saline infusion (t-PA vs. UK p = .30) Scanning electron microscopy was performed 4 hr and 48 hr after thrombolysis. No differences between thrombolytic agents was noted in terms of residual thrombus and vessel characteristics. The data suggest that t-PA and urokinase are effective, with no clear advantage of one agent over the other. PMID- 1909761 TI - The importance of empathy as an interviewing skill in medicine. PMID- 1909762 TI - [Clinical study on fleroxacin in surgical infections]. AB - We conducted clinical studies on fleroxacin (FLRX), a new pyridone carboxylic acid derivative, for the treatment of periproctal abscess, secondary infections (due to wounds, burns or surgical operations), mastitis or areolitis and others with once daily dose of 200 mg or 300 mg. We obtained the following results. Clinical efficacy was evaluated in total 27 cases including periproctal abscess 11, secondary infection 8, mastitis or areolitis 6, phlegmon 1 and infected atheroma 1. Clinical efficacies were rated as excellent in 14, good in 9, fair in 4 cases. The overall efficacy rate was 85.2%. Bacteriological studies identified 14 strains of aerobic Gram-positive organisms, 12 of aerobic Gram-negative organisms and 6 of anaerobic organisms. The overall bacteriological efficacies were: eradicated in 26 strains, unchanged 2 and unidentified 4, hence the eradication rate was 92.9%. As for side effects, anorexia and nausea were observed in one of the 27 cases. In clinical laboratory tests, slight elevations of GPT and BUN were observed in 1 case each. We consider FLRX to be a useful antimicrobial agent at once daily dose for surgical infections. PMID- 1909763 TI - [Clinical evaluation of fleroxacin in gynecological infections]. AB - Fleroxacin (FLRX), a new quinolone oral antibacterial agent, was studied in the field of obstetrics and gynecology, and the following results were obtained. 1. Clinical efficacy was evaluated in 105 patients (intrauterine infection 38, adnexitis 28, extragenital organ infection 29, others 10), with an exclusion of 9 patients out of a total of 114 patients. FLRX was orally administered at 200 mg or 300 mg once daily. 2. Clinical efficacy rates were 37/38 (97.4%) in intrauterine infection, 26/28 (92.9%) in adnexitis, 29/29 (100%) in extragenital organ infection and 10/10 (100%) in others. 3. Efficacy rates classified by isolated organisms were 23/23 (100%) in single infections by Gram-positive organisms, 11/13 (84.6%) in those by Gram-negative organisms, 8/9 (88.9%) in those by anaerobic organisms and 15/19 (78.9%) in mixed infections. 4. Side effects were observed in 4 cases (3.5%); gastrointestinal disorder with diarrhea and diarrhea in 1 patient each and insomnia in 2 patients. In laboratory examination, eosinophilia and elevation of GOT and GPT were noted in 1 patient each (1.9%). Based on the above results, we consider that FLRX is a useful drug for the obstetrical and gynecological infections. PMID- 1909765 TI - [Identification of Mycobacterium avium, Mycobacterium intracellulare, and Mycobacterium tuberculosis complex by Gen-Probe Rapid Diagnostic System]. AB - DNA probe testing for Mycobacterium avium, Mycobacterium intracellulare and Mycobacterium tuberculosis complex (MTC) was performed using Gen-Probe Rapid Diagnostic System (Gen-Probe Inc., San Diego, Calif., U.S.A.). By DNA probe test carried out blindfold for 48 mycobacterial strains with code numbers obtained from Kyoto University (Prof. F. Kuze), 13, 7, and 5 strains were identified as to be M. avium, M. intracellulare, and MTC, respectively. The diagnostic specificity and sensitivity of this testing were 100%. In this experiment, % hybridization of M. avium complex (MAC) and MTC were 25-55% and 45-52%, respectively. DNA probe test for 54 MTC strains including M. tuberculosis, M. bovis, M. africanum and M. microti revealed that 53 strains, except for one strain donated as a niacin negative M. tuberculosis, reacted with MTC probe but not with MAC-probes. The one exceptional strain reacted with both the MTC- and M. avium-probes. However, when ten colonies randomly isolated from this strain on 7H11 agar plate were subjected to the DNA probe test again, all of these colonies reacted with M. avium probe, but not with MTC probe. Moreover, one representative colony was found to have alpha-antigen specific for the MAC. PMID- 1909764 TI - [Suppression of gamma-interferon induced HLA-DR antigen expression on normal and transformed keratinocytes by 1,25 (OH)2 vitamin D3]. AB - Recently, it has been shown that 1,25 (OH)2 Vitamin D3 (VD3) shows growth inhibition and enhances differentiation of keratinocytes in vitro. To elucidate the further effect of VD3 on keratinocytes, we studied the effect of recombinant human gamma interferon (IFN-gamma) and VD3 on the expression of HLA-DR antigen and MHC class I antigen on 3 normal and 6 transformed keratinocytes by means of FACS analysis. IFN-gamma (500 JRU/ml, 72 hr) induced the expression of HLA-DR antigen on 3/3 normal keratinocytes, 3/4 trichilemmoma and 1/2 squamous cell carcinoma cell lines. When these cells were cultured with both IFN-gamma and VD3 at the same time, the expression of HLA-DR antigen was significantly decreased. Sequential treatment of these cells with IFN-gamma and VD3 (each 72 hr), or vice versa, showed significant suppression of HLA-DR antigen expression. The fluorescens intensity of class I antigen was increased after IFN-gamma treatment, however, this effect is inhibited when the cells were treated with combination of IFN-gamma and VD3. PMID- 1909766 TI - TRH-Gly, a precursor of TRH, alters GH secretion in acromegaly. AB - We explored effects of a precursor of thyrotropin (TSH)-releasing hormone (TRH), TRH-Gly, on growth hormone (GH) secretion in acromegaly. Intravenous injection of TRH-Gly produced a profound increase in GH secretion in eight, decrease in two, and no response in five out of a total fifteen patients. The magnitude of GH responsiveness to TRH-Gly was significantly correlated with that induced by TRH (r = 0.824, P less than 0.01). In contrast, TRH-Gly did not induce secretion of TSH or prolactin. The present data suggest that TRH-Gly may participate in regulating GH secretion in some patients with acromegaly and that TRH-Gly-induced GH secretion may be due at least in part to TRH-associated mechanisms underlying GH secretion. PMID- 1909768 TI - Aquatic ape theory and fossil hominids. AB - While most older palaeo-anthropological studies emphasise the similarities of the fossil hominids with modern man, recent studies often stress the unique and the apelike features of the australopithecine dentitions, skulls and postcranial bones. It is worth reconsidering the features of Australopithecus, Homo erectus and Homo neanderthalensis in the light of the so-called Aquatic Ape Theory (AAT) of Hardy and Morgan, and to compare the skeletal parts of our fossil relatives with those of (semi)aquatic animals. Possible convergences are observed with proboscis monkeys, beavers, sea-otters, hippopotamuses, seals, sea-lions, walruses, sea-cows, whales, dolphins, porpoises, penguins and crocodiles. PMID- 1909767 TI - Immunogenicity and protective efficacy of pertussis toxin subunit S1 produced by Bacillus subtilis. AB - Pertussis toxin (PT) subunit S1 was produced in Bacillus subtilis as a secretory protein designated BacS1. BacS1 was partially purified and used to immunize mice. The sera were tested for PT-neutralizing antibodies and for protective capacity in a mouse model. Unlike previous findings with recombinant S1 from Escherichia coli, the recombinant BacS1 protein induced antibodies that were both neutralizing and protective. An adjuvant was necessary for efficient immunization with BacS1 but not with PT. Of the four adjuvants tested, aluminium phosphate gel was insufficient whereas Freund's incomplete adjuvant, Klebsiella lipopolysaccharide and Ribi's monophosphoryl lipid A-trehalose dimycolate emulsion all resulted in protective antibody production in NIH mice. PMID- 1909769 TI - Targetted destruction of PC3 mitochondria by ETYA: a 'Trojan horse' membrane suicide molecule. AB - The reported incorporation of ETYA in place of arachidonic acid, itself enriched in mitochondria, and the autooxidation of alkyne groups, as indicated by spontaneous chemiluminescence, encompasses several features appropriate for an organelle-specific 'suicide' molecule. In point of fact, ETYA selectively destroys PC3 mitochondria. PMID- 1909770 TI - Lupus anticoagulants, anticardiolipin antibodies, and fetal loss. A case-control study. AB - BACKGROUND: Lupus anticoagulants and anticardiolipin antibodies are antiphospholipid antibodies that have been associated with fetal loss, but they have not been shown unequivocally to be a risk factor for this event. METHODS: To estimate the risk of fetal loss in association with these antibodies, we conducted a hospital-based case-control study of 331 women with spontaneous abortion or fetal death (case patients) and 993 controls. The subjects were included in the study only if they reported that they had had no previous spontaneous fetal loss. Each control was a pregnant woman who, in the same period of pregnancy as a case patient, had not had a fetal loss. Lupus anticoagulants were identified in blood samples through a series of coagulation tests, and IgG anticardiolipins by an enzyme-linked immunosorbent assay. Each subject was interviewed in person to obtain information on potential confounding variables, such as sociodemographic characteristics and medical conditions. RESULTS: Lupus anticoagulants were found in blood from 17 case patients (5.1 percent) and 38 controls (3.8 percent). The crude odds ratio for the association between lupus anticoagulants and fetal loss was 1.36 (95 percent confidence interval, 0.75 to 2.43); the odds ratio adjusted for confounders was 1.42 (95 percent confidence interval, 0.72 to 2.80). An IgG anticardiolipin level of 5 units or more was found in 4 case patients (1.2 percent) and 15 controls (1.5 percent). The crude and adjusted odds ratios for fetal loss were 0.80 (95 percent confidence interval, 0.26 to 2.41) and 1.28 (95 percent confidence interval, 0.38 to 4.21), respectively. CONCLUSIONS: There is not apparent justification for considering lupus anticoagulants or IgG anticardiolipins to be risk factors for fetal loss among women who present with spontaneous abortion or fetal death and have had no previous spontaneous fetal loss. PMID- 1909772 TI - [Pharmacokinetic basis of mannitol administration in the treatment of raised ICP]. AB - To study the most effective way of mannitol administration for the treatment of raised intracranial pressure (ICP), pharmacokinetics of mannitol were analysed, and the relationship among mannitol concentration, serum osmolality and changes of intracranial pressure (ICP) were examined in cats. 10%, 20% and 30% of mannitol were made and intravenously administrated with the same volume and speed (0.667 ml/kg/min) for 15 minutes to each mannitol concentration group of cats. Sequential changes of ICP were monitored and serial mannitol concentration, serum osmolality and electrolytes were then performed. Changes of mannitol concentration showed a biexponential curve and best fitted to the two-compartment model analysis. There was a strong positive correlation (r = 0.9286) between mannitol concentration and extrinsic serum osmolality. The disposition of mannitol in cats was similar to that which had been reported in dogs and humans. The distribution half-time was faster in 30% mannitol, but the elimination half time was similar in all groups. The integrated values of mannitol concentration difference between the central (Cc) and the peripheral compartment (Pc) were greatly correlated with the changes of ICP reduction during mannitol administration (for 15min). The time to vanish the mannitol concentration difference between Cc and Pc showed strong reverse correlation with the time to reach the lowest ICP level. The result indicates that the more rapidly mannitol was administrated, the more rapidly the concentration difference between the two compartments was created, and, the higher the effective osmolality was developed, then, the more profound and prolonged ICP reduction can be obtained.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1909771 TI - Dopamine activation of the arachidonic acid cascade as a basis for D1/D2 receptor synergism. AB - Understanding the actions of the neurotransmitter dopamine in the brain is important in view of its roles in neuropsychiatric illnesses. Dopamine D1 receptors, which stimulate both adenylyl cyclase and phospholipase C, and D2 receptors, which inhibit them, can nevertheless act synergistically to produce many electrophysiological and behavioral responses. Because this functional synergism can occur at the level of single neurons, another, as yet unidentified, signalling pathway activated by dopamine has been hypothesized. We report here that in Chinese hamster ovary (CHO) cells transfected with the D2 receptor complementary DNA, D2 agonists potently enhanced arachidonic acid release, provided that such release has been initiated by stimulating constitutive purinergic receptors or by increasing intracellular Ca2+. In CHO cells expressed D1 receptors, D1 agonists exert no such effect. When D1 and D2 receptors are coexpressed, however, activation of both subtypes results in a marked synergistic potentiation of arachidonic acid release. The numerous actions of arachidonic acid and its metabolites in neuronal signal transduction suggest that facilitation of its release may be implicated in dopaminergic responses, such as feedback inhibition mediated by D2 autoreceptors, and may constitute a molecular basis for D1/D2 receptor synergism. PMID- 1909773 TI - Surgery for focal epilepsy in the older patient. AB - Eight of the 237 patients who received a surgical procedure for intractable partial epilepsy at the Mayo Clinic during a 3-year period were 50 years of age or older. All patients had disabling partial seizures of several years in duration that were refractory to antiepileptic drug medication. A neuroimaging identified epileptogenic lesion prompted referral for surgical treatment in three patients. The only clinically significant morbidity associated with surgery in the eight patients was a transient exacerbation of an aphasia in a patient who underwent a left frontal corticectomy. All eight patients had a favorable seizure outcome, and three patients postoperatively are seizure free. Epilepsy surgery may be an appropriate alternate therapy for select patients in the sixth decade of life or older with medically refractory partial seizures. PMID- 1909774 TI - Captopril as adjunctive treatment in catamenial epilepsy. PMID- 1909775 TI - Comparative examination of various rectal tubes and contrast media for the reduction of intussusceptions. AB - The hydrodynamic influence of different rectal tube sizes, contrast media, and heights of the fluid column on hydrostatic reduction of intussusception was analyzed in vitro. Enemas were performed in dead rabbits to compare the filling speed of bowel with a liquid and a gaseous contrast medium. For hydrostatic reduction, tubing and rectal tube with a large caliber and a low viscosity contrast medium achieved a higher filling speed of colon and are expected to provide a higher force of reduction on the intussusceptum. A rectal tube with a large caliber can be more useful than an increase of the column height. Filling bowel with carbon dioxide was approximately 7 times faster than with meglumine sodium diatrizoate. Theoretical considerations allow the hypothesis that a gaseous medium provides a faster and steadier reduction than a liquid. PMID- 1909776 TI - Coexisting nephrolithiasis and cholelithiasis in premature infants. AB - Though the coexistence of nephrolithiasis and cholelithiasis in premature infants is extremely rare, we report four patients seen in a two year period. All patients weighed less than 1100 grams at birth, developed severe bronchopulmonary dysplasia, and all had Grade III or IV bilateral intraventricular hemorrhages. All four infants received prolonged furosemide therapy lasting at least 28 consecutive days. The renal stones disappeared in all four upon cessation of therapy, while in none have the gallstones disappeared after a mean follow-up period of 13 months. Ultrasound was superior in identifying and monitoring these stones. Their presence resulted in manipulating diuretic therapy which then was shown to limit renal and possibly biliary complications. PMID- 1909777 TI - Pyruvate carboxylase deficiency: a benign variant with normal development. AB - The devastating nature of a pyruvate carboxylase deficiency is underscored by the uniformly fatal outcome of the neonatal (French) type and the severely disabling and ultimately fatal outcome of the infantile (North American) type. We report a 7-y-old girl with metabolic and biochemical features of the North American phenotype. Remarkably, the clinical course has been benign with preservations of motor and mental abilities. The residual enzyme activity in cultured skin fibroblast homogenates was 1.8% and cross-reacting material was present in normal abundance and electrophoretic mobility. She has had several episodes of metabolic acidosis with elevated lactate, pyruvate, alanine, beta-hydroxybutyrate, acetoacetate, lysine, and proline values, and undetectably low aspartate concentrations. These crises have been managed by rehydration and bicarbonate therapy. We are unable to provide a satisfactory explanation for the uniquely benign clinical course that has been experienced by this patient. PMID- 1909778 TI - Demonstration of an unstable variant of pyruvate dehydrogenase protein (E1) in cultured fibroblasts from a patient with congenital lactic acidemia. AB - The deficiency of pyruvate dehydrogenase enzyme complex causes congenital lactic acidemia and devastating neurologic abnormalities in newborns and children. In the majority of cases, the basic defect appears to be in the pyruvate dehydrogenase (E1) component, which consists of two subunits, alpha and beta. Whereas some patients are deficient of a single subunit, in other patients both subunits of E1 are missing. To find out why two proteins were deficient, we investigated the cultured fibroblasts of a female patient who had missing E1 alpha and E1-beta protein bands on Western blot. Radiolabeling immunoprecipitation studies with 35S-methionine revealed that patient fibroblasts synthesized normal sized precursor E1-alpha and E1-beta proteins, which were presumably transported into mitochondria and processed into normal sized mature proteins. However, pulse-chase analysis showed that alpha- and beta-proteins were degraded rapidly compared to normal. Our findings proved that alpha- and beta subunits were synthesized and processed normally but failed to form a stable structure for incorporation into the pyruvate dehydrogenase complex. PMID- 1909779 TI - Metabolism of 1-13C-propionate in vivo in patients with disorders of propionate metabolism. AB - Metabolism of propionate in human subjects was studied using bolus administration of 1-13C-propionate i.v. or orally. The study population consisted of five patients with propionic acidemia (PA), eight with methylmalonic acidemia (MMA; four responsive to vitamin B12), one each with multiple carboxylase deficiency and transcobalamin-II deficiency, and five healthy volunteers. Concentrations of 1-13C-propionate were measured in blood in three patients with PA, two with MMA, and two controls. Breath samples were obtained at intervals during 3 h after the dose, isotopic enrichment of 13CO2 was measured, and the cumulative percentage of recovery of 13C was calculated from the individual's predicted resting energy expenditure. Recovery of 13CO2 and half-time of 1-13C-propionate in PA were significantly less than normal. The same parameters in MMA were below normal, but significantly greater than in PA. Recovery of 13CO2 was well correlated with clinical severity in PA, but did not correlate in MMA. Differences between MMA and PA may indicate different distribution of propionate pools, differences in inducibility of residual enzyme activities, or an alternate pathway for decarboxylation of propionate available in MMA but not PA. Only one patient with PA demonstrated increased 13CO2 production during biotin treatment. In a B12 responsive MMA patient, no differences were noted within 2 d of initiating treatment with B12, but there was an increase in 13CO2 production after 4 mo. Recovery of 13CO2 was normal in the patient with transcobalamin-II deficiency before and after treatment with vitamin B12.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1909780 TI - Ontogeny of thyrotropin releasing hormone and precursor peptide in the rat. AB - Thyrotropin releasing hormone (TRH) and its precursor peptide pGlu-His-Pro-Gly (TRH-Gly) were measured in serum and in a variety of tissues of developing rats using specific RIA. TRH and TRH-Gly immunoreactivities were detected in most tissues. TRH concentrations were highest in pancreas, in which mean (+/- SEM) TRH concentrations were 138 +/- 20 pmol/g wet tissue 2 d before birth and 644 +/- 80 and 586 +/- 86 pmol/g, respectively, 2 and 5 d after birth. Hypothalamic TRH levels gradually increased from 4 d before birth (12 +/- 2.5 pmol/g) to 77 d of postnatal age (348 +/- 33 pmol/g). Hypothalamic concentrations were lower than levels in pancreas until 13 d of age. The mean serum TRH level at 2 d was 80 +/- 20 pmol/L and fell to the adult range by 21 d. TRH-Gly concentrations were highest in small gut (371 +/- 64 pmol/g) during the neonatal period, falling gradually to adult levels (33 +/- 4.8 pmol/g) by 35 d. Mean hypothalamic TRH-Gly concentrations increased to a peak of 62 +/- 4.5 pmol/g at 13 d, falling thereafter. High TRH-Gly concentrations (greater than 100 pmol/g) also were observed in pancreas (at d 2), kidney, and pituitary gland (at d 21). Serum TRH Gly concentrations were highest (mean 417 +/- 26 pmol/L) on the 2nd postnatal day and gradually decreased to the adult level by 35 d. Changes in the TRH-Gly/TRH ratio were inversely correlated with tissue TRH concentrations in hypothalamus, pancreas, and liver.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1909781 TI - Enteral immunoglobulins for treatment of protracted rotaviral diarrhea. PMID- 1909782 TI - Endotoxic shock after transfusion of contaminated red blood cells in a child with sickle cell disease. PMID- 1909784 TI - Expression of the gene encoded by a family of macronuclear chromosomes generated by alternative DNA processing in Oxytricha fallax. AB - Hypotrichous ciliated protozoa, such as Oxytricha fallax, produce tiny chromosomes during generation of the transcriptionally active macronucleus. The 81-MAC family of macronuclear chromosomes is produced by alternative DNA processing, such that the chromosomes share a common region of 1.6 kbp. Transcription of a 1.3 kb mRNA from the common region has been analyzed. Transcription starts very near the telomere (34 bp), in a 23 bp region of pure A + T DNA. Polyadenylation sites are very near the other telomere (26 bp), also in a region of nearly pure A + T DNA. Three introns are clustered in the first third of the gene. Intron removal can follow polyadenylation, and the order of removal is not fixed. All three known sequence versions of the 81-MAC chromosomes are represented in the mRNA pool, with no evidence of any further versions. The A + T sequences surrounding the transcription starts and polyadenylation sites are conserved among versions. Introns have conserved 5' and 3' ends and a putative branch-point sequence (YYRAT), but otherwise are highly diverged and are AT-rich. A single long open reading frame, interrupted by the three introns, encodes a homolog of known mitochondrial solute carriers, and contains the codon TAA, which does not encode 'stop,' but a conserved glutamine; TAG appears also to encode glutamine. The results significantly enlarge the small data set of transcription start and polyadenylation sites, of intron features, and of translation signals for hypotrichs. PMID- 1909783 TI - Regulation of potassium conductance by prostaglandins in cultured renal epitheloid (Madin-Darby canine kidney) cells. AB - Madin-Darby canine kidney (MDCK) cells form arachidonic acid metabolites following stimulation of several hormones known to modify the ion conductances at the plasma membrane. The present study has been performed to elucidate the influence of arachidonic acid on the electrical properties of subconfluent MDCK cells. As a result, arachidonic acid (1 or 10 mumol/l) leads to a transient hyperpolarization of the cell membrane, followed by a transient depolarization and a second, sustained hyperpolarization. The effects are inhibited by cycloxygenase inhibitor indomethacin (1 mumol/l). The initial transient hyperpolarization is mimicked by prostaglandin E2 (PGE2, 0.1 mumol/l), the sustained hyperpolarization by both PGE2 (0.1 mumol/l) and PGF2 alpha (0.1 mumol/l). The transient hyperpolarization is paralleled by an increase of potassium selectivity and a decrease of cell membrane resistance and is thus the result of increased potassium conductance. The transient depolarization is paralleled by an increase of chloride selectivity, reflecting an increase of chloride conductance. The sustained hyperpolarization is paralleled by an increase of cell membrane resistance, and increase of potassium selectivity and a decrease of chloride selectivity, and is thus the result of decreasing chloride conductance. The observations reveal a role of prostaglandins in the regulation of ion conductances in MDCK cells, which could well participate in the transport regulation by hormones. PMID- 1909785 TI - Ssp RF1, a novel class-II restriction endonuclease from Synechococcus RF-1 recognizing 5'TT/CGAA-3'. PMID- 1909786 TI - The restriction enzyme AlwNI is blocked by overlapping methylation. PMID- 1909787 TI - Two novel restriction endonucleases from Pseudomonas aeruginosa. PMID- 1909788 TI - The IGLJ6 joining segment as a STS in the human immunoglobulin lambda light chain constant region gene locus (located at 22q11). PMID- 1909789 TI - The IGLVA gene as a STS in the human immunoglobulin lambda light chain variable gene locus (located at 22q11) PMID- 1909790 TI - Interferon-gamma treatment in mice experimentally infected with Trichinella spiralis. AB - Interferon-tau (IFN-tau) treatment of Trichinella spiralis-infected BALB/c mice was investigated. The therapeutic regimen consisted of daily intraperitoneal injection of 10(4) U murine IFN-tau for 7 days, starting at 2 weeks post infection. Striated muscle samples (diaphragm, thigh) were collected at 4, 8 and 12 weeks after infection. The muscle larval burden, the degree of encystation and the digestion of T. spiralis larvae were investigated. Furthermore, immunohistochemical studies of the inflammatory cell infiltrate around encysted larvae were performed. The results demonstrated an influence of IFN-tau treatment on the CD4+ and CD8+ subset distribution during the immune response but revealed no difference in the degree of encystation or digestion of encapsulated larvae as compared with control values. PMID- 1909792 TI - Quantitative immunocytochemical staining for recombinant tissue-type plasminogen activator in transfected Chinese hamster ovary cells. AB - Tissue-type plasminogen activator (tPA) is a serine protease which cleaves plasminogen to its active form, plasmin. tPA plays a physiologic role in hemostasis, wound healing, and embryogenesis. Therapeutically, recombinant human tPA is used as a thrombolytic in myocardial infarction. Although production of therapeutic quantities of tPA in Chinese hamster ovary (CHO) cells transfected with the human gene for tPA is practical, production costs remain high. One important factor which determines the ultimate cost of tPA (or any other recombinant protein expressed in mammalian cells) is its production level on a per cell basis. We have used postembedding immunocytochemical staining with colloidal gold to study the subcellular localization of tPA in CHO cells expressing recombinant tPA (rCHO) in an effort to understand the factor(s) which might limit secretion. Staining for tPA was evaluated visually and by morphometric analysis and was specific and reproducible. Serially passaged rCHO showed no significant change in staining density over 31 serial passages. Staining density was greatest over dilated cisternae of the rough endoplasmic reticulum and nuclear envelope. Golgi stacks and large acid phosphatase-positive vacuoles (probably lysosomes) were also heavily stained. Staining of lysosomal vacuoles suggested that rCHO might be degrading nascent tPA. Incubation of rCHO with 125I-tPA showed that the cells were not internalizing tPA from the media. These results suggest that rCHO fail to secrete a portion of the tPA they synthesize and that it is degraded in lysosomes. This observation may have important implications on the choice of expression systems for efficient production of large quantities of recombinant proteins. PMID- 1909791 TI - Follistatin and activin: a potential intrinsic regulatory system within diverse tissues. PMID- 1909793 TI - Transforming growth factor-beta and activin inhibit basal secretion of prolactin in a pituitary monolayer culture system. AB - Incubations of rat anterior pituitary cells with transforming growth factor (TGF) beta 1 for 48 hr suppressed the secretion of basal prolactin (PRL) in a dose dependent manner (ED50, 100 pg/ml). Activin, a gonadal hormone processing cysteine distribution similar to TGF beta, also suppressed basal PRL secretion, but it was less effective (ED50, 4 mg/ml). Treatment with TGF beta 1 significantly suppressed basal PRL secretion from the pituitary after 24 hr and up to 72 hr of incubation. TGF beta 1 also inhibited thyrotropin-releasing hormone-mediated PRL secretion and activin inhibited thyrotropin-releasing hormone-mediated PRL secretion slightly, but significantly. In addition, we also measured the secretion of growth hormone by cultured pituitary cells treated with TGF beta 1 or activin for 24 to 72 hr. TGF beta 1 and activin showed an opposite effect on growth hormone secretion; TGF beta stimulated and activin inhibited basal secretion of growth hormone. These results suggest that TGF beta 1 is a potent inhibitor of basal secretion of PRL by the pituitary, and both TGF beta 1 and activin play a multifunctional role in basal secretion of pituitary hormones. PMID- 1909794 TI - Monoclonal antibody produced against partially purified sporozoite antigen inhibits invasion of cells by sporozoites of avian Eimeria species. AB - Previous studies showed that molecules of in vitro-cultured primary turkey kidney cells bound to 23-, 40-, and 60- to 65-kDa antigens of sodium dodecyl sulfate solubilized sporozoites of Eimeria adenoeides. Similar binding to antigens of three other species of avian Eimeria, E. tenella, E. acervulina, and E. meleagrimitis, is now reported. Strips containing the most avidly bound sporozoite antigen (approximately 40 kDa) were excised from the sodium dodecyl sulfate-polyacrylamide gels on which E. adenoeides antigens had been electrophoretically separated. The strips were homogenized and injected into mice to produce hybridoma cell lines. Twelve cell lines secreting monoclonal antibodies (McAb) that reacted with E. adenoeides sporozoites were detected. One of these McAb, H11C3, reacted with structures in the anterior tip of sporozoites of E. adenoeides and five other species of avian Eimeria. When included in the inoculation medium, this McAb significantly inhibited invasion of cultured kidney cells by sporozoites of E. adenoeides and E. tenella. In contrast, when the sporozoites were pretreated with McAb H11C3 and then washed free of the antibody, no inhibition of invasion was observed. PMID- 1909795 TI - Significant qualitative differences exist between thyrotropin and prolactin secretory dynamics induced by pituitary cell swelling. AB - Cell swelling produced by a variety of techniques is a potent stimulus intensity related inducer of an immediate secretory burst of thyroid-stimulating hormone (TSH) and prolaction (PRL) secretion from anterior pituitary cells. A 2-min "square wave" exposure to either hyposmolarity or isotonic urea induced stimulus intensity-correlated TSH and PRL secretory bursts peaking within 3 min, but the PRL zenith occurred 1 min later than that of TSH. With continuous exposure to these stimuli, TSH secretion rapidly decreased and remained only slightly above the unstimulated rate after 5 min. PRL secretion fell to and remained below the unstimulated level after 10 min. After stopping the stimulus, another secretory burst ("off" response) occurred with PRL, but not with TSH. A progressive "ramp" increase in stimulus intensity over 18 min induced a corresponding gradual increase in TSH secretion; there was a progressive depression, rather than increase, in PRL secretion during the stimulus ramp, with an off response secretory burst when the stimulus was discontinued. Removal of extracellular Ca2+ or addition of verapamil to the medium did not alter the dynamics of hyposmolarity-induced TSH secretion, but markedly altered those of PRL secretion; there was no off response PRL secretion and a hyposmolar ramp induced a corresponding gradual increase in PRL secretion, with a return to baseline after removing the stimulus. The dramatic qualitative differences in the response of the thyrotroph and lactotroph may reflect differences between the cell types in the size of secretory vesicles, membrane potential, the mechanism of exocytosis, and/or the role of Ca2+ influx across the plasmalemma. PMID- 1909797 TI - Three cases of severe mania successfully treated with high-dosage lithium carbonate. AB - Three female patients suffering from severe mania, who failed to respond to increasingly high dosages of highly potent neuroleptics, were put on a high-dose regime of lithium carbonate. With rapidly increasing daily doses of lithium carbonate, blood levels of approximately 1.3-1.51 mmol/l were achieved. When high lithium levels had been attained the patients showed a considerable improvement between 75 and 82 percent on the Bech-Rafaelsen Scale. At the same time it proved possible to reduce additional medication. Not toxic effects of lithium carbonate were observed. The consequences for clinical practice (e.g. shortened duration of hospitalization) are discussed. PMID- 1909796 TI - Glomerulopressin production by isolated rat liver after amino acid infusion. AB - The infusion of certain amino acids, such as serine, alanine, and proline (SAP), has been shown to increase the glomerular filtration rate, whereas branched chain amino acids (BCAA) leucine, isoleucine, and valine fail to modify the glomerular filtration rate. It has been suggested that this effect of amino acids on the glomerular filtration rate is mediated by the action of the hormone glomerulopressin. The purpose of this work was to study the action of SAP and BCAA on glomerulopressin production. Livers isolated from rats were perfused with (i) Krebs-Ringer-Bicarbonate, (ii) SAP, or (iii) BCAA. Results indicate that glomerulopressin production is stimulated by SAP, but inhibited by BCAA. PMID- 1909798 TI - 4-Hydroxy-2-cyclopentenone: an anti-Pseudomonas and cytotoxic component from Passiflora tetrandra. AB - 4-Hydroxy-2-cyclopentenone is responsible for the anti-bacterial activity of an extract of leaves from Passiflora tetrandra with minimum inhibitory doses (MID) of ca. 10 micrograms/disk against Escherichia coli, Bacillus subtilis, and Pseudomonas aeruginosa. 4-Hydroxy-2-cyclopentenone is also cytotoxic to P388 murine leukemia cells (IC50 of less than 1 microgram/ml). PMID- 1909799 TI - John Bowlby: an interview. Interview by Virginia Hunter. PMID- 1909801 TI - Is there a role for the psychoanalytic psychotherapist with a patient dying of AIDS? PMID- 1909800 TI - Issues in the psychoanalytic treatment of single females over thirty. PMID- 1909802 TI - Autoerotism to secondary narcissism: clarifying the developmental line. PMID- 1909803 TI - Reading Freud and returning to Lacan: an essay review. PMID- 1909804 TI - A reconsideration of the Freud-Tausk-Deutsch relationship. PMID- 1909805 TI - The text-body connection: character as fetish in The Plumed Serpent. PMID- 1909806 TI - War as a holding environment: an analysis of Empire of the Sun. PMID- 1909807 TI - Thrombolysis for pulmonary embolism. PMID- 1909808 TI - Two explanations of nurse practitioner interactions and participatory decision making with physicians. AB - The purpose of this study was to test a theoretical model that integrated two explanations of nurse practitioner interaction and participatory decision making with physicians. The two explanations were derived from technology theory and social exchange theory. Nurse practitioners (N = 38) responded to a four-scale magnitude estimation instrument measuring each of four concepts in the model: complexity, expected benefit-cost ratio of interaction, interaction, and participatory decision making. Predictions derived from both theories were supported. Nurse practitioner decisions about interaction with physicians were influenced by the dynamics of social exchange with physicians, as well as the technological requirements of primary care. The findings offer nurse practitioners new strategies for managing professional exchanges on behalf of their patients. PMID- 1909809 TI - [Diagnostic cost-effectiveness of bronchofiberoscopy in pleural effusions]. AB - With the aim of testing the cost-effectiveness of diagnostic fiberbronchoscopy in pleural effusions, the results obtained in a study of 46 patients in whom pleural effusion was the only indication for this diagnostic technique was analyzed. Patients were divided into two groups based on whether they presented pleural effusion of unkown ethiology (group A) or non-localized primary metastatic effusion (group B). Two out of 28 patients in group A, and 5 out of 18 in group B were diagnosed by means of fiberbronchoscopy. It is concluded that given the good tolerance and low morbidity of this exam, the diagnostic cost-effectiveness justifies its performance in such situations. Possible modifications in the indications that could influence its utility are discussed. PMID- 1909810 TI - [Sequential administration of norethisterone and natural oral progesterone during premenopausal menstrual cycle disorders]. AB - A sequential treatment either with norethisterone or with oral natural micronized progesterone was administered, after randomization, to 80 women consulting for premenopausal disorders of the menstrual cycle. In all cases, the initial aspect of the endometrium showed a progesterone deficit with hyperplasia in 50 per cent of cases. At the third and sixth month of treatment, none of the biopsies presented hyperplastic characteristics whether after norethisterone or oral progesterone. However, three months after suspension of treatment, the proliferative or hyperplastic characteristics reappeared in 24 per cent of cases in the norethisterone group, and in 10 per cent of cases in the oral progesterone group. The administration of norethisterone induced a decrease in plasma levels of estradiol (E2), FSH and LH, and sex-hormone-binding globulin (SHBG) (p less than 0.001). No modification was observed during treatment with oral progesterone. The plasma levels of HDL-cholesterol and triglycerides were decreased by norethisterone (p less than 0.001-0.02). A slight decrease in phospholipids was also observed in this group. Treatment with oral natural micronized progesterone therefore offers an attractive alternative for the treatment of premenopausal menstrual disorders. PMID- 1909811 TI - [Orbital neurofibrosarcoma. Clinical and etiological study; apropos of a case]. AB - This case report is about a relapsing conjunctive sarcoma affecting a 67 year old woman, involved with Von Recklinghausen's neurofibromatosis. Surgical orbital exenteration was necessary for curative treatment and reconstruction used a temporal muscle flap. Through this report, emphasis is placed on diagnosis difficulties and possibility of serious development concerning these malignant tumors in the scope of neurofibromatosis. PMID- 1909812 TI - [Radiation protection of the small intestine in the lesser pelvis using an inflatable silicon prosthesis]. AB - The combination of radiotherapy and surgery plays a major role in treating pelvic cancer. However, this technique is chiefly limited by the radiosensitivity of the small bowel following postoperative radiotherapy. In this situation the small bowel is not protected because of its lack of mobility. A radioprotective prosthesis is presented which is readily removable and whose purpose is to push the small bowel out of the pelvis during radiotherapy, thus protecting it from radiotherapy. If required, a simple system allows the prosthesis to be emptied and refilled between courses of radiotherapy, if required, without reoperation. This technique has been used in 4 patients: 2 had rectal carcinoma secondary to ulcerative colitis in one case and to Crohn's disease in the other; the other 2 cases were recurrent rectal carcinoma, one of which was partially resectable. When radiotherapy was completed the prosthesis could be deflated and removed through a short incision under local anesthetic. In the medium term, no small bowel complications were observed in spite of high-dose radiotherapy. When used for radiosensitive pelvic tumors, this technique combines low cost and ease of use with very low morbidity and the possibility of administering high-dose radiotherapy. PMID- 1909813 TI - Survivors of Hodgkin's disease: prevention of sequelae. AB - Increasing numbers of patients are surviving Hodgkin's disease in their youth, creating an ever larger cohort who need careful attention to long-term preventive medicine in their older years. Vigilance is especially needed for those who received laparotomy, splenectomy, and irradiation for early stage I through stage III disease, the majority of whom are destined to be long-term survivors. With the frequent migration of the young, these patients often fall under the care of a physician other than their original oncologist. The diligent internist, oncologist, emergency room physician, and general practitioner can avoid several simple pitfalls in the long-term care of these young patients now entering middle age. PMID- 1909814 TI - [The place of HR-CT in the diagnosis of calcifying and ossifying disease processes of the eye and the orbit]. PMID- 1909815 TI - Pharmacokinetic properties of an Escherichia-coli-produced recombinant plasminogen activator (BM 06.022) in rabbits. AB - The recombinant plasminogen activator BM 06.022 consists of the kringle 2 and the protease domains of human t-PA and is unglycosylated because of its expression in Escherichia coli. The pharmacokinetic properties of BM 06.022 following intravenous injection over 1 min were characterized in anesthetized male New Zealand white rabbits. BM 06.022 was injected at doses of 50, 100, 200, and 400 kU/kg bw (n = 5-6/dose). Activity concentrations in plasma were determined using an indirect spectrophotometric assay. The maximum plasma concentration and the area under the plasma concentration vs. time curve (AUC0-00) of BM 06.022 increased linearly with dose. The systemic clearance ranged from 2.5 to 3.0 ml.min-1.kg-1 and did not show dose-dependency, in contrast to alteplase which was studied at doses of 200, 400, 800, and 1600 kU/kg. A direct comparison of clearance rates of BM 06.022 and alteplase at doses of 200 and 400 kU/kg each revealed a 8.5-fold slower clearance rate of BM 06.022. The majority (18/23) of rabbits with BM 06.022 injection showed a pharmacokinetic profile which was best characterized by a one-compartment model in contrast to alteplase (10/23). The dose-groups of BM 06.022 showed an average dominant half-life ranging from 11.6 to 15.4 min, which was about five-times longer than the dominant half-life values of alteplase (2.3 to 4.5 min). Assuming a two-compartment model in the remaining animals, the initial alpha-phase of BM 06.022 accounted for 40.1 +/- 13.2% (n = 5) of the total AUC, whereas the alpha-phase of alteplase accounted for 82.7 +/- 3% (n = 13) of the total AUC. PMID- 1909816 TI - Influence of synthetic sulfated bis-lactobionic acid amides on tissue-type plasminogen activator release. PMID- 1909817 TI - Prenatal lead exposure in the rat during the third week of gestation: long-term behavioral, physiological, and anatomical effects associated with reproduction. AB - Sprague-Dawley dams were administered lead acetate (0.1%) in their drinking water from Day 14 of gestation to parturition to determine whether exposure of the fetus to elevated lead (Pb) levels during a period of rapid differentiation of the hypothalamic-pituitary-gonadal (HPG) axis would disrupt HPG function in adulthood. At birth, offspring from 20 Pb-treated and 10 control dams were weighed and 2 litter representatives from each sex were fostered to untreated dams. Animals were weaned at 26 days of age and subsequently group housed by sex and treatment. Blood Pb levels in prenatally exposed pups were below the limits of detectability at weaning. Female offspring from Pb-treated dams were found to have a significant delay in the day of vaginal opening. In a sample of lead exposed females, 50% were found to exhibit prolonged and irregular periods of diestrous which was accompanied by an absence of observable corpora lutea when they were euthanized at 83 days of age. Male offspring from these dams were found to have decreased sperm counts at 70 and 160 days of age and to exhibit significantly less territorial scent marking and masculine sex behavior in adulthood compared to controls. Azoospermia was observed in 1 lead exposed animal at 70 days of age and 2 animals at 160 days. Enlarged prostates were observed in Pb-exposed males measured at 160 days, but other sex organ weights were normal. Volume of the sexually dimorphic nucleus of the preoptic area of the hypothalamus in adulthood was significantly reduced by approximately 35% in Pb-exposed males. Pulsatile release of gonadotropins, measured in castrated adult animals of both sexes, revealed irregular release patterns of both FSH and LH in some Pb animals which were not observed in controls. The overall pattern of results suggests that multiple levels of the HPG axis can be affected by exposure to Pb during a period of gestation when structures related to the HPG axis are undergoing rapid proliferation. These data indicate that lead exposure during this period places the exposed animal at significant risk for reduced reproductive capacity in adulthood. PMID- 1909818 TI - Calcium mediation of cyanide-induced catecholamine release: implications for neurotoxicity. AB - Exposure of rat pheochromocytoma (PC12) cells to KCN (1.0-10 mM) over a 30-min period stimulated secretion of dopamine (DA) and decreased intracellular DA content. Addition of KCN (10 mM) to rat frontal cortex slices preloaded with 1-[7 3H]norepinephrine ([3H]NE) increased secretion of NE over a 10- to 30-min incubation period. In PC12 cells release of DA by KCN was nearly abolished in calcium-free media or by prior addition of diltiazem, a calcium channel antagonist. Release of [3H]NE from rat cortical slices by cyanide was only partly inhibited by diltiazem suggesting that intracellular calcium may be involved in this response. In PC12 cells KCN also produced a dose-related release of the DA precursor dihydroxyphenylalanine, without altering intracellular stores. Levels of the DA metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) were enhanced at lower concentrations of KCN. These observations indicate cyanide elicits exocytotic release of neurotransmitters in a calcium-dependent manner and also show that cyanide alters catecholamine metabolism. These actions of cyanide may be important in CNS symptoms of intoxication. PMID- 1909819 TI - Red blood cells augment transport of reactive metabolites of monocrotaline from liver to lung in isolated and tandem liver and lung preparations. AB - Monocrotaline (MCT) is a pyrrolizidine alkaloid that causes pulmonary hypertension in rats by mechanisms which remain largely unknown. MCT is thought to be activated in the liver to a reactive intermediate that is transported to the lung where it causes endothelial injury. Our previous pharmacokinetic work demonstrated significant sequestration of radioactivity in red blood cells (RBCs) of rats treated with [14C]MCT. To determine whether this RBC sequestration might be important in the transport of reactive MCT metabolites, we compared the effect of inclusion of RBCs in the perfusion buffer on the extent of covalent binding of [14C]MCT to rat lungs in tandem liver-lung preparations. The potential effect of RBCs in stabilizing reactive intermediates was evaluated by preperfusion of isolated liver preparations with [14C]MCT with and without RBCs, separation and washing of the RBC fraction, and subsequent (90 min later) perfusion of washed RBCs or buffer alone in isolated perfused lungs. Covalent binding to lung tissues was determined by exhaustive methanol/chloroform extractions of unbound label from homogenized lung tissue followed by scintillation counting of residual 14C. Covalent binding was expressed as picomole MCT molecular weight equivalents/mg protein. Comparison of the relative capability of these isolated organ preparations for conversion of MCT to polar metabolites was done by extraction and HPLC analysis of perfusate at the end of the experiment. Isolated livers converted 65-85% of MCT to polar metabolites compared with less than 5% conversion in the isolated lungs. Inclusion of RBCs in the buffer of tandem lung liver preparations perfused with 400 microM [14C]MCT increased the covalent binding to the lung from 97 +/- 25 (buffer alone) to 182 +/- 36 (buffer + RBC) pmol/mg protein. At the end of these perfusions, RBCs contained 1552 +/- 429 pmol/mg hemoglobin of which 333 +/- 98 pmol/mg hemoglobin resisted exhaustive solvent extraction. After 90 min at room temperature, buffer with 400 microM [14C]MCT preperfused in isolated livers resulted in covalent binding to isolated perfused lung of 0.8 +/- 0.4 pmol/mg protein while washed RBCs isolated from buffer of similar liver preperfusions preparations resulted in 53 +/- 7 pmol/mg protein bound to lung. Control groups perfused with 400 microM [14C]MCT in buffer or buffer + RBCs through isolated lungs only resulted in covalent binding of 2 +/ 1 or 1 +/- 0.6 pmol/mg protein respectively. We conclude: (1) RBCs significantly augment the transport of lung reactive MCT metabolites from the liver to the lung.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1909820 TI - White cells protect donor blood against bacterial contamination. AB - The possible beneficial role of white cells (WBCs) in donor blood has been investigated with respect to their capacity to remove bacteria. Preparations of buffy coat and whole blood, containing as well as reduced of WBCs, were inoculated with Staphylococcus epidermidis, S. aureus, Escherichia coli, Pseudomonas aeruginosa, and Propionibacterium species. Upon storage at room temperature, the presence of WBCs resulted in a reduction of the bacterial content. Units inoculated with S. epidermidis and E. coli were completely cleared of bacteria within 5 to 24 hours. On the other hand, S. aureus, after an initial reduction in number, started to multiply. In WBC-reduced units, the initial bacterial content remained unchanged for 5 hours, but the bacteria then exhibited vigorous growth within 48 hours in buffy coat and slower growth in whole blood. Propionibacterium sp. did not grow with or without WBCs. P. aeruginosa did not grow in buffy coat but showed a growth pattern similar to that of S. aureus in whole blood. The presence of WBCs in the donor blood during the first hours after collection thus seems to rid the blood of at least some species of bacteria. These results indicate that it would be favorable not to perform WBC reduction during blood collection and that several hours of contact can be needed to obtain sterility. PMID- 1909822 TI - Let's look at human immunodeficiency virus look-back before leaping into hepatitis C virus look-back. PMID- 1909821 TI - Complement activation by artificial blood substitute Fluosol: in vitro and in vivo studies. AB - A perfluorocarbon blood substitute, Fluosol, is undergoing clinical trials as an adjunct to chemotherapy. The adverse effects associated with its administration have been postulated to result from complement activation. When gel electrophoresis and Western blotting of Fluosol are used after its incubation with serum, activated C3 and factors Bb and H are bound to the Fluosol particles in a time-dependent fashion, which suggests that complement activation with Fluosol, as does that with zymosan, occurs on the surface of the particles. Paradoxically, it is found, both by the measurement of Fluosol-bound C3d and by fluid-phase C5a, that lower concentrations of Fluosol cause greater amounts of complement activation, which suggests a complex interaction of activators and inhibitors that changes as the available surface area is decreased. Studies performed with bystander red cell-bound C3d demonstrated in vivo complement activation occurring in six patients receiving Fluosol as an adjunct to chemotherapy for colon cancer. In two patients, there was a marked increase in red cell-bound C3d after Fluosol infusion; these two patients also developed adverse reactions during Fluosol infusion. These studies suggest that the Fluosol surface plays a major role in the initiation and regulation of complement activation that is seen during Fluosol infusion. PMID- 1909823 TI - Controversies in transfusion medicine: Du testing: Pro. PMID- 1909824 TI - Clathrin light chains: arrays of protein motifs that regulate coated-vesicle dynamics. AB - Polymerization of clathrin triskelions into clathrin coats and subsequent disassembly by the heat shock protein hsc70 control receptor-mediated pathways of intracellular transport. The clathrin light chains are major regulatory elements in these processes. These polypeptides consist of linear arrays of functional domains with distinctive sequence motifs. Comparison of unicellular and multicellular eukaryotes reveals differences in the numbers of clathrin light chains and in the functional domains they contain. PMID- 1909825 TI - Bacteriophage SPO1 middle transcripts. PMID- 1909826 TI - Classifying simple and complex cells on the basis of response modulation. AB - Hubel and Wiesel (1962; Journal of Physiology, London, 160, 106-154) introduced the classification of cortical neurons as simple and complex on the basis of four tests of their receptive field structure. These tests are partly subjective and no one of them unequivocally places neurons into distinct classes. A simple, objective classification criterion based on the form of the response to drifting sinusoidal gratings has been used by several laboratories, although it has been criticized by others. We review published and unpublished evidence which indicates that this simple and objective criterion reliability divides neurons of the striate cortex in both cats and monkeys into two groups that correspond closely to the classically-described simple and complex classes. PMID- 1909827 TI - Expression of human immunodeficiency virus (HIV) in naturally infected peripheral blood mononuclear cells: comparison of a standard co-culture technique with a newly developed microculture method. AB - Peripheral blood mononuclear cells (PBMCs) from 29 patients infected with human immunodeficiency virus (HIV) were cultured by two different methods. One was the standard co-culture technique, the other a newly developed microculture method. In this assay 10(6) PBMCs were cultivated in 250 microliters medium, no activating agents or allogeneic cells were present. P24 antigen production measured by this method was found in 7 out of 11 PBMC cultures of patients in the Walter Reed (WR) stage 1 or 2, whereas only 4 samples were positive by the co culture procedure. Cultures from patients in the later stages of the disease (WR 5/6) showed a higher p24 production by the co-culture method than by the microculture assay. It is assumed that rapidly growing HIV strains can be better assessed by the co-culture method which may select for these strains. P24 expression can be more easily obtained by the microculture technique even in cases where slowly replicating strains may be present. In conclusion, results from the microculture procedure described may be a useful supplementation to findings observed by the co-culture method. PMID- 1909828 TI - Complement activation pathways associated with islet cell surface antibody (ICSA) derived from child patients with insulin-dependent diabetes mellitus (IDDM). AB - We studied the pathways of complement activation associated with the islet cell surface antibody (ICSA) obtained from sera of 7 patients (age less than 15 years) with insulin dependent diabetes mellitus (IDDM). The target cells were 51CR labelled rat islet cells and the complement source was human AB serum. Complement dependent antibody mediated cytotoxicity (CAMC activity) was obtained using the percentage of cytotoxicity. CAMC activity of untreated sera was significantly inhibited by treating with EGTA or EDTA (p less than 0.001). The CAMC activity of EDTA-treated sera was significantly lower than that of EGTA-treated sera (p less than 0.001). In the inactivated human AB serum, it was lower than that of EGTA treated sera (p less than 0.05), but not different from that of EDTA-treated sera. These results show that the complement activation associated with ICSA in patients occurred not only via the classical pathway but also via the alternative pathway. PMID- 1909829 TI - [A histochemical study of testicular mast cells from patients with male infertility]. AB - The proteoglycan of the mast cells from human testes was analyzed using histochemical techniques. Testicular biopsies were obtained from 50 with idiopathic male infertility, 13 with obstructive azoospermia, 6 with varicocele and 14 normal men. To identify the proteoglycan, nitrous acid treatment and chondroitinase ABC digestion were carried out in addition to specific staining procedures using Alcian Blue pH 1.0 and high iron diamine. In all clinical groups, the mast cells which contained heparin were predominant. However, in the idiopathic male infertility group, the mast cells which contained chondroitin sulfate increased significantly. This type of mast cells were rarely seen in normal testicular tissue, whereas in the testes of patients with idiopathic male infertility, 20 percent or more mast cells contained chondroitin sulfate. This observation demonstrates that a change in mast cell subclass occurs in the testes of the patients with idiopathic male infertility and implies that the mast cells play an important role in the etiology of this disorder. PMID- 1909830 TI - [A basic study on cefpirome]. AB - The antibacterial activity of cefpirome (CPR), a new parenteral cephalosporin antibiotic having a cyclopentenopyridine group in the 3-position side chain, was evaluated against Neisseria gonorrhoeae and concentrations in human kidney and prostate was determined. The minimum inhibitory concentrations (MICs) of CPR against N. gonorrhoeae isolated clinically in our out-clinic (34 strains of non PPNG and 20 of PPNG) were less than or equal to 0.003-0.1 microgram/ml in non PPNG group and 0.006-0.1 microgram/ml in PPNG group. The 90% of MICs (MIC90s) was 0.1 microgram/ml in the non-PPNG group and 0.05 microgram/ml in the PPNG group. The concentration in the prostate was determined in 30 cases with benign prostatic hypertrophy. The maximum values was 52.8 micrograms/g at 15 minutes after administration of 1 g of CPR. The levels of CPR were gradually decreased with the lapse of time. The prostatic tissue concentration was 17.9 micrograms/g at 60 min., 10.1 micrograms/g at 180 min., 7.22 micrograms/g at 320 min. and 2.70 micrograms/g at 360 min. There was a positive correlation between concentration of the prostate and plasma collected at the time of the prostate. The concentration of CPR in human kidney, 90-100 min. after administration of 1 g to 4 cases with renal tumor, was 107-148 micrograms/g in the renal cortex, and 80.6 88.6 micrograms/g in the renal medulla. The concentration in kidney was higher than that in the plasma in all cases. In conclusion, CPR is suggested to be a useful drug for urological infection. PMID- 1909831 TI - [Bacteriological and clinical studies on fleroxacin in male gonococcal urethritis]. AB - We performed basic and clinical studies on the effects of a new oral antimicrobial agent, fleroxacin (FLRX), a new quinolone derivative in male gonococcal urethritis. The antibacterial activity of FLRX against clinical strains of Neisseria gonorrhoeae was roughly comparable to that of norfloxacin and ofloxacin. FLRX was administered to 58 males with gonococcal urethritis. Two different schedules of administration were adopted. One was a single-dose of 300 mg given orally (17 cases) and the other was the oral administration of 200 mg once a day for 3 to 10 days (41 cases). Clinical evaluation was made according to the criteria of the Japanese UTI Committee. The overall efficacy rate was 98% (49/50). For complications of Chlamydia trachomatis (11 cases), the efficacy rate was 90.9% (10/11). No subjective or objective adverse reaction occurred. PMID- 1909832 TI - Enteral feeding tubes: placement by using fluoroscopy and endoscopy. AB - Fluoroscopy and endoscopy are both effective for guiding placement of enteral feeding tubes, but the relative advantages and limitations of the two methods are less clear. Consequently, we studied 104 consecutive patients referred for primary fluoroscopic placement of a Frederick-Miller feeding catheter. Success rate, fluoroscopic and room times, and tube position were determined. Unsuccessful fluoroscopic placement was followed immediately by an endoscopic attempt. The success rate for fluoroscopic placement was 90% (94/104), with the tube placed into the jejunum in 53% and into the duodenum in 47%. The fluoroscopic and room times for successful fluoroscopic placements were 8.6 +/- 5.6 min (mean +/- SD) and 21.7 +/- 8.4 min, respectively. For the 10 unsuccessful placements, the fluoroscopic and room times were 16.2 +/- 5.4 min (mean +/- SD) and 45.6 +/- 18.4 min, respectively. Both time differences were significant statistically. Endoscopic placement was successful in all seven patients in whom it was attempted, with a mean time of 13.4 min. The tubes placed endoscopically were in the jejunum in 29% and in the duodenum in 71%. Our results show that fluoroscopic and endoscopic placement of enteral feeding tubes is highly effective. Fluoroscopic time in successful cases is usually less than 15 min. Endoscopic placement of feeding tubes is successful after fluoroscopic failure. PMID- 1909833 TI - Indications for radiography in patients with acute ankle injuries: role of the physical examination. AB - A prospective study was performed to test the hypothesis that a thorough physical examination can eliminate the need for a large number of radiographs obtained in patients with acute ankle trauma. Two hundred one patients were seen in the emergency department for acute ankle trauma and referred to the department of radiology for ankle radiographs. Radiology residents performed a brief but thorough physical examination of the ankle in all 201 patients. Solely on the basis of a strict set of physical examination criteria (examination for gross deformity, instability, crepitation, focal bony tenderness, severe soft-tissue tenderness, moderate or severe soft-tissue swelling, and ecchymosis), the radiologists determined whether or not the radiographs were indicated. All patients, irrespective of the physical examination, underwent ankle radiography, and the results were correlated with those of the physical examination. On the basis of the results of the physical examinations, 101 (50%) of the radiologic studies were not indicated. In only one of these patients was a fracture seen on radiographs. The radiograph in this case showed a small avulsion fracture of the dorsal aspect of the talus that was clinically insignificant (no cast or surgery was required). Our results suggest that a brief but thorough physical examination can eliminate the need for a large percentage of radiographs ordered in patients with acute ankle trauma. PMID- 1909834 TI - Arteriopathy and coarctation of the abdominal aorta in children with mucopolysaccharidosis: imaging findings. AB - Eight children with mucopolysaccharidosis I (MPS I), representing 33% of all children with MPS I seen at our institution during an 18-year period, developed hypertension. Five of these hypertensive children also exhibited symptoms of aortic coarctation. The radiographic evaluation of four of these children with MPS I (three with Hurler syndrome, MPS I H, and one with Scheie disease, MPS I S) and arteriopathy affecting the thoracic aorta, abdominal aorta, and visceral and renal arteries is presented. Hypertension developed in all four children before they were 4 years old; three had differences between upper- and lower-extremity blood pressures. Irregular narrowing of the abdominal aorta with either multiple minor asymmetric wall lesions (n = 2) or abrupt concentric narrowing (n = 2) was present in all children as shown by aortography (n = 3), sonography (n = 3), MR imaging (n = 2), and/or autopsy (n = 1). A variety of other vessels also were involved, including the ascending aorta (n = 1) and vertebral (n = 1), axillary (n = 1), intercostal (n = 2), lumbar (n = 2), mesenteric (n = 3), renal (n = 2), and iliac arteries (n = 3). Autopsy in one child demonstrated thickened heart valves, narrowing of the coronary arteries, and irregularity of the aorta due to deposition of mucopolysaccharide material within the intima. Our series demonstrates various facets of the arteriopathy of MPS I as shown by sonography, MR imaging, and angiography. PMID- 1909835 TI - Percutaneous needle puncture for treatment of ileal obstruction caused by migration of a gastrostomy tube. PMID- 1909836 TI - Thrombosis and thrombolysis in unstable angina. AB - Pathophysiology of unstable angina involves spasm, plaque rupture, activation of platelets, and coagulation. The incidence and frequency of intracoronary thrombus formation are presently under active assessment in order to establish the potential benefit of thrombolytic therapy. A preliminary study was conducted in patients admitted in our coronary care unit for unstable angina with typical clinical and electrocardiographic criteria and with early coronary angiogram. After exclusion of 4 patients with left main coronary stenosis or contraindications for thrombolysis, 16 patients received thrombolytic infusion and 14 underwent a second coronary angiogram. Seven patients had an intracoronary thrombus (6 nonocclusive, 1 occlusive) and at the second angiogram only 3 nonocclusive thrombi were modified (1 disappeared, 2 were reduced). Moreover, the quantitative Coronary Angiography Analysis System (CAAS) in the 11 cases suitable for analysis did not show any significant changes, especially in the Ambrose type IIB lesions. In-hospital clinical outcome was not influenced by thrombolytic therapy (5 ischemic recurrences, 1 fatal myocardial infarction, 4 emergency and 4 elective revascularization procedures). This short series is in agreement with the literature data. Only one third of patients with active unstable angina remains refractory to conventional therapy. The transient benefit of thrombolysis is limited to patients with demonstrated intracoronary thrombi. Clinical or angiographic improvement are not always in correlation and until now do not seem able to prevent short-term recurrences or the need for revascularization procedures. PMID- 1909837 TI - Positive direct antiglobulin tests in myeloma patients. Occurrence, characterization, and significance. AB - Review of direct antiglobulin testing (DAT) in 88 patients with multiple myeloma (MM) and five with Waldenstrom's macroglobulinemia revealed 26 cases with a positive DAT. Twenty-two of these had immunoglobulin G-M protein, three had light chain MM, and one had immunoglobulin A-MM protein. None of the immunoglobulin GD MM (n = 2), nonsecretory MM (n = 5), or Waldenstrom's macroglobulinemia patients (n = 5) were positive. None of the patients had hemolysis attributable to the adsorption of the M protein. The serum concentration of M protein was higher in DAT-positive patients (57.6 +/- 3.8 g/L, mean +/- SEM) than in the negative ones (35.7 +/- 6.4 g/L; probability value of the difference was less than 0.01). The erythrocyte eluates from DAT-positive patients contained a single immunoglobulin, of the same class as the M protein, and did not react with a panel of ABO compatible erythrocytes. Addition of melphalan during incubation did not affect the results. The M protein of DAT-positive patients was of immunoglobulin G-3 subclass in 7 of 10 patients. A positive direct antiglobulin test frequently is seen in patients with multiple myeloma, the reaction is due to passive adsorption of the M protein onto the erythrocytes, is most frequently observed with immunoglobulin G3-MM, and usually does not produce hemolysis. PMID- 1909838 TI - Reversible malnutrition in AIDS. PMID- 1909839 TI - Screening recommendations for gestational diabetes mellitus. AB - As a result of extensive experiences in multiple centers and a review of the current literature, we conclude that a plasma glucose level obtained 1 hour after a 50 gm oral glucose challenge is the "best" gestational diabetes mellitus screening test. This universal screening is performed at least once during pregnancy. The screening threshold should be no higher than 140 mg/dl, or an unacceptable loss in sensitivity occurs. Universal screening for gestational diabetes mellitus is justified by morbidity reduction, cost, and protocol simplicity and ease. PMID- 1909840 TI - Hexamethylmelamine chemotherapy for persistent or recurrent epithelial ovarian cancer. AB - The purpose of this study was to determine the activity and toxicity of hexamethylmelamine chemotherapy in patients with persistent or recurrent epithelial ovarian cancer. Forty-nine women received hexamethylmelamine 100 to 150 mg/day for 14 days, repeated at 4-week intervals. All patients had previously received at least one chemotherapy regimen, and 46 (94%) had received cisplatin. Among 25 patients with clinically measurable disease there were three complete and two partial responses, for an objective response rate of 20%. The mean progression-free interval for responders was 38.6 months versus 9.6 months for nonresponders or patients with nonmeasurable disease (p less than 0.001). Thirteen patients are alive, eight with no clinical evidence for disease. Only four patients discontinued therapy because of toxic reactions. Hexamethylmelamine appears to be a well-tolerated drug with activity against ovarian cancer previously treated with cisplatin. PMID- 1909841 TI - Treatment of fetal supraventricular tachycardia with flecainide acetate after digoxin failure. AB - Transplacentally administered digoxin is the drug of choice for the treatment of fetal supraventricular tachycardia. We describe a case of fetal supraventricular tachycardia associated with fetal hydrops that did not respond to digoxin treatment because of a lack of transplacental passage. In contrast, flecainide acetate crossed the placenta and cured the fetus. The clinical implications of this new treatment are discussed. PMID- 1909842 TI - Lipid peroxidation in neonatal mouse brain subjected to two different types of hypoxia. AB - To elucidate the role of free radicals in the pathogenesis of neonatal hypoxic encephalopathy, we determined the content of thiobarbituric acid reactants (TBARs), as an index of lipid peroxidation related with a free radical reaction, in the brains of newborn mice during hypoxia and recovery from hypoxia. Hypoxic stress was induced by 100% nitrogen gas breathing (N2 group) or 100% carbon dioxide gas breathing (CO2 group). TBARs increased with 20 minutes of hypoxia and returned to the control level during the recovery period in both groups. The increase in TBARs in the CO2 group was greater than that in the N2 group. These results may suggest that free radical reaction occurs during the hypoxic period and that CO2 hypoxia is more effective on free radical production in the newborn brain than N2 hypoxia. PMID- 1909843 TI - Effects of nitroglycerin and diltiazem on well-developed coronary collateral circulation in conscious dogs. AB - The purpose of the present study was to compare the effects of nitroglycerin and diltiazem on coronary collateral circulation. Studies were conducted in 8 conscious dogs instrumented for the measurement of left circumflex coronary artery (LCCA) flow, subendocardial segment lengths in areas perfused by the LCCA, and left anterior descending coronary artery (LAD). Brief, repeated LCCA occlusions sufficiently developed collateral vessels for the resting metabolic requirement in the LCCA region. One week following the cessation of repeated LCCA occlusions, two-minute coronary occlusions with and without drug pretreatment were performed on separate days. The ischemic responses to coronary occlusions were not altered by diltiazem (50 micrograms/kg, IV), but nitroglycerin (5 micrograms/kg, IV) attenuated myocardial ischemia definitely. The authors conclude that nitroglycerin produces greater effects than diltiazem in attenuating myocardial ischemia in the collateral dependent zone when effects of each drug on systemic and coronary circulation were minimized by pretreatment with small doses. PMID- 1909844 TI - Synteny mapping of human chromosome 8 loci in cattle. AB - Four genes having homologous loci on the short arm of human chromosome 8 have been mapped to two different bovine syntenic groups. The gene coding for the tissue-type plasminogen activator mapped with GSR, a human chromosome 8 marker, of syntenic group U14 while lipoprotein lipase and the medium and light neurofilament polypeptide genes were shown to be syntenic with the human chromosome 9 marker GGTB2 of syntenic group U18. PMID- 1909845 TI - Concentrations of amino acids in the plasma of neonatal foals with septicemia. AB - Concentrations of amino acids in the plasma of 13 neonatal foals with septicemia were compared with the concentrations of amino acids in the plasma of 13 age matched neonatal foals without septicemia. Analysis of the results revealed significantly lower concentrations of arginine, citrulline, isoleucine, proline, threonine, and valine in the plasma of foals with septicemia. The ratio of the plasma concentrations of the branched chain amino acids (isoleucine, leucine, and valine) to the aromatic amino acids (phenylalanine and tyrosine), was also significantly lower in the foals with septicemia. In addition, the concentrations of alanine, glycine, and phenylalanine were significantly higher in the plasma of foals with septicemia. Therefore, neonatal foals with septicemia had significant differences in the concentrations of several amino acids in their plasma, compared with concentrations from healthy foals. These differences were compatible with protein calorie inadequacy and may be related to an alteration in the intake, production, use, or clearance of amino acids from the plasma pool in sepsis. PMID- 1909846 TI - Oxygen-induced hypercarbia in obstructive pulmonary disease. AB - We investigated the mechanisms responsible for oxygen-induced hypercarbia in ventilator-dependent patients with advanced chronic obstructive pulmonary disease (COPD). To quantitate the effects of oxygen (O2) on respiratory drive, we determined the CO2 recruitment threshold (PCO2 RT) in 10 mechanically ventilated patients under normoxic (PaO2 = 67 +/- 7 mm Hg) and hyperoxic (PaO2 = 370 +/- 67 mm Hg) conditions. PCO2 RT is a measure of the CO2 responsiveness of the mechanically unloaded respiratory system and, as such, is independent of mechanical impedance and respiratory muscle strength. After O2 supplementation, PCO2 RT increased from 42 +/- 6 to 45 +/- 6 mm Hg (p less than or equal to 0.05), indicating a suppression of so-called hypoxic respiratory drive. The effect of hyperoxia on the dead space to tidal volume ratio (VD/VT) and CO2 elimination (VCO2) was studied in 6 patients. Measurements were made at identical ventilator settings, thus eliminating breathing pattern- and respiratory work-related effects on these variables. VD/VT rose from 0.49 +/- 0.09 to 0.55 +/- 0.06 (p less than or equal to 0.05), but VCO2 remained constant at 0.21 L/min. We discuss why measuring O2-induced changes in minute ventilation, VCO2, PaO2, and VD/VT in spontaneously breathing patients is insufficient to distinguish between gas exchange- and respiratory drive-related mechanisms for hypercarbia. Based on the O2-induced increase in PCO2 RT, we conclude that so-called suppression of hypoxic drive plays an important role in the pathogenesis of this disorder. PMID- 1909847 TI - Drug-resistant tuberculosis. PMID- 1909849 TI - Cost effectiveness of treating asymptomatic HIV infection. PMID- 1909848 TI - Incidence of non-A, non-B hepatitis after screening blood donors for antibodies to hepatitis C virus and surrogate markers. AB - OBJECTIVE: To compare the effect of screening blood donors for antibodies to hepatitis C virus (anti-HCV) on the incidence of non-A, non-B hepatitis in recipients with that of screening blood donors for antibodies to hepatitis B core antigen (anti-HBc) and elevated alanine aminotransferase levels. DESIGN: Cohort analysis of serum samples from donors and recipients. Recipients were followed for 12 months to determine the occurrence of non-A, non-B hepatitis. SETTING: The blood-transmitted viruses unit and the liver unit of a university teaching hospital. SUBJECTS: A total of 250 patients who had open heart surgery and their 3142 blood donors. MEASUREMENTS: Donor sera were tested for anti-HCV by enzyme linked immunosorbent assay (ELISA) and, in the event of a positive result, by recombinant immunoblot assay (RIBA). Antibodies to anti-HBc and serum alanine aminotransferase (ALT) levels were also measured. Measurements of anti-HCV and ALT activity in recipients were done before transfusion and at regular intervals during follow-up. MAIN RESULTS: Of the 250 transfusion recipients, 40 developed non-A, non-B hepatitis. Of the 3142 donors, 70 were positive for anti-HCV by ELISA, 440 were positive for anti-HBc, and 177 had alanine aminotransferase levels between 0.67 and 1.33 mukat/L. The sensitivity (87%), specificity (89%), positive predictive value (59%), and negative predictive value (97%) of blood donor screening were higher for anti-HCV than for anti-HBc (82%, 36%, 21%, and 91%, respectively) and 70%, 29%, and 91%, respectively). The expected number of donors excluded because of the presence of anti-HCV was considerably smaller than that of donors with positive results for surrogate markers of hepatitis. CONCLUSION: Screening blood donors for the presence of anti-HCV is more accurate than screening for surrogate markers (anti-HBc and ALT) and protects more effectively against post-transfusion non-A, non-B hepatitis. PMID- 1909850 TI - Rapid enzymatic method for the measurement of mannitol in urine. AB - A previously described method for mannitol in urine has been modified and improved. End product inhibition by fructose in the mannitol dehydrogenase method for mannitol has been minimized; the assay is linear over a sample mannitol concentration range of 0-12 mmol/L; no significant interference from other sugars or sugar alcohols could be demonstrated. The method is precise (within-batch CV less than 1%), rapid and shows excellent recovery of mannitol in spiked samples. Comparison with gas liquid chromatography shows excellent correlation (r = 0.994) between the two methods. PMID- 1909851 TI - Epileptogenic effect of hypoxia in the immature rodent brain. AB - The response to cerebral hypoxia/ischemia may be different in the neonate compared to other age groups. An in vivo model was developed in the rat to determine whether there are age-dependent differences in the effects of hypoxia on electroencephalographic (EEG) activity. EEG recordings were obtained from Long Evans hooded rats deprived of oxygen at five ages: postnatal days 5 to 7, 10 to 12, 15 to 17, 25 to 27, and 50 to 60. Oxygen concentration was varied from 0, 2, 3, and 4% between animals. EEGs were recorded in all animals before, during, and at 1 hour after exposure to the hypoxic condition and at 1 to 7 days afterward in a subset of animals. All animals were deprived of oxygen until the onset of apnea and bradycardia to 20 to 40% of baseline heart rate values. Hypoxia resulted in isoelectric EEG significantly more frequently in the animals deprived of oxygen at postnatal days 25 to 27 and 50 to 60 than in the younger age groups. A highly significant effect was that the animals deprived at postnatal days 5 to 17 revealed a high incidence of epileptiform EEG activity during hypoxia. In contrast, the older animals exhibited only rare isolated EEG spikes before reaching an isoelectric EEG. The severity of hypoxia-induced epileptiform EEG changes was highest in the animals subjected to moderately hypoxic conditions (3% and 4% oxygen) at postnatal days 10 to 12. Furthermore, epileptiform changes persisted for hours to days following prolonged episodes of hypoxia in the younger animals. This study demonstrates a unique response of the immature brain to exhibit epileptiform activity during hypoxia. PMID- 1909852 TI - Neocortical damage during HIV infection. AB - Clinical and pathological evidence of subcortical central nervous system (CNS) damage is observed commonly in patients with human immunodeficiency virus (HIV) encephalitis. Whether other CNS regions are also affected has not been well studied. We report neocortical damage in patients with HIV encephalitis. Using quantitative techniques, we demonstrate statistically significant thinning of the neocortex, with a loss of large cortical neurons. Qualitative and quantitative assessments of neocortical neuropil reveal a loss of synaptic density and vacuolation of dendritic processes. Failure to demonstrate an association of these changes with the presence of HIV antigens suggests that neocortical damage may be an indirect effect of HIV infection of the CNS. PMID- 1909853 TI - Processing of the lactococcal extracellular serine proteinase. AB - Activity of the lactococcal cell envelope-located serine proteinase depends on the presence of membrane-associated lipoprotein PrtM. To differentiate between the action of the proteinase and the action of PrtM in the process of proteinase maturation, an inactive form of the lactococcal proteinase was constructed. This was done by mutating one of the three amino acids thought to constitute the active site of the enzyme. The secreted form of this inactivated proteinase was the same size as the inactive secreted form of the proteinase produced in the absence of PrtM. Both inactive proteinases are larger than the active proteinase. Isolation of proteinase by washing lactococcal cells carrying the complete proteinase gene in a Ca(2+)-free buffer was prevented by the absence of prtM or the absence of a functional active site. We propose that PrtM, during or after membrane translocation of the proteinase, effects the autoproteolytic removal of the N-terminal pro region of the proteinase. Subsequent C-terminal autodigestion results in the release of the enzyme from the lactococcal cells. PMID- 1909854 TI - Characterization of physicochemical forces involved in adhesion of Listeria monocytogenes to surfaces. AB - This study investigated the physicochemical forces involving the adhesion of Listeria monocytogenes to surfaces. A total of 22 strains of L. monocytogenes were compared for relative surface hydrophobicity with the salt aggregation test. Cell surface charges and hydrophobicity of L. monocytogenes Scott A were also determined by electrophoretic mobility, hydrophobic-interaction chromatography, and contact angle measurements. Electrokinetic measurements indicated that the strain Scott A has a negative electrophoretic mobility. Physicochemical characterization of L. monocytogenes by various methods indicates that this microorganism is hydrophilic. All L. monocytogenes strains tested with the salt aggregation test method aggregated a at very high ammonium sulfate molarities. The hydrophobicity-interaction chromatography results show that L. monocytogenes Scott A cells do not adhere to octyl-Sepharose unless the pH is low. Results from contact angle measurements showed that the surface free energy of strain Scott A was 65.9 mJ.m-2, classifying this microorganism as a hydrophilic bacterium. In addition, the interfacial free energy of adhesion of L. monocytogenes Scott A estimated for polypropylene and rubber was lower than that for glass and stainless steel. However, these theoretical implications could not be correlated with the attachment capabilities of L. monocytogenes. PMID- 1909855 TI - Exaggerated prolactin response to thyrotropin-releasing hormone in infertile women with the luteinized unruptured follicle syndrome. AB - Ten cases of luteinized unruptured follicle (LUF) syndrome out of 250 women with unexplained infertility were detected on ultrasonography, giving a frequency of 4%. Hormonal analysis revealed lower serum progesterone levels at mid-luteal phase in LUF cases, suggesting a link between LUF syndrome and inadequate luteal phase. Prolactin response to thyrotropin-releasing hormone was exaggerated in LUF cases as compared with ovulatory cases. Aberrant prolactin release may be a contributory factor in the pathophysiology of the LUF syndrome. PMID- 1909856 TI - [Structure-activity relationship of cephalosporins. II. Effect of oxygen containing functional groups on the biological activity od cephalosporins- derivatives of 7-aminocephalosporanic acid]. AB - The statistical analysis of 529 compounds belonging to the group of cephalosporins revealed a significant influence of oxygen-containing descriptors of the radical at position 7 in the cefem nucleus on the biological activity of the compounds. It was concluded that prediction of the antimicrobial properties of the antibiotics by the pattern recognition was possible with using factors reflecting the presence and space arrangement of the following functional groups in the cephalosporin molecules:-OH (phenolic group), C-O-C (ether), C = O (ester, amide) and -O- (in the heterocycle). The results of the study were compared with the data on the impact of nitrogen-containing descriptors on the biological activity of cephalosporins and practical recommendations for synthesis of new active compounds were proposed. PMID- 1909857 TI - [Structure-activity relationship of cephalosporins. III. Effect of sulfur containing functional groups on the biological activity of cephalosporins- derivatives of 7-aminocephalosporanic acid]. AB - The relationship between the in vitro antimicrobial activity of cephalosporin antibiotics and the presence and space arrangement of sulfur-containing descriptors of the radical at position 7 in the cefem nucleus was studied. It was noted that the sulfur-containing fragments were markedly less frequent in the structures of the known cephalosporins than the nitrogen- and oxygen-containing descriptors. It was concluded that at present information related only to two of the fragments under investigation might be used as characteristics in predicting antimicrobial activity of cephalosporins by the pattern recognition. On the basis of the studies there were defined two principle paths for synthesis of new antibiotics: introduction into the molecule structure of the functional groups providing with high probability improvement of the antimicrobial properties and preparation of compounds containing descriptors whose impact on the biological activity is not known. PMID- 1909858 TI - [Antibacterial and therapeutic effectiveness of a pectin from sea grass Zostera]. AB - The kinetics of the antibacterial activity of zosterin, a polysaccharide preparation of a sea grass belonging to Zoster, was studied. By its chemical structure zosterin is a low ++methoxylated pectin. In vitro the preparation markedly inhibited the growth of ++Gram-negative and ++Gram-positive organisms: S. aureus, E. coli, Y. pseudotuberculosis, S. typhimurium and Ps. aeruginosa. On a model of experimental pseudotuberculosis++ infection caused by oral contamination of mice F1 (CBA X C57B1) with a suspension of Y. pseudotuberculosis zosterin was shown to have a therapeutic effect. It protected 30 to 40 per cent of the animals when administered per os simultaneously with or 24 hours after the contamination. The results are in favour of the zosterin further investigation as a preparation useful in prevention of intestinal infections in persons being in contact with the patients. PMID- 1909859 TI - Genetics of diabetes. Genes and environment. AB - Many other autoimmune and chronic diseases exhibit marked geographic variation in incidence, which has been attributed to environmental differences across populations (Hutt and Burkitt, 1986). The results of our international IDDM research have provided evidence for the importance of large genetic variations in the frequency of HLA susceptibility genes between racial groups and countries. One may speculate that differences in the prevalence of susceptibility genes for other chronic diseases exist and significantly contribute to the geographic patterns of incidence of these disorders. Other autoimmune diseases are known to have epidemiological features similar to those described for IDDM. Although they are also characterized by an underlying HLA-related susceptibility, environmental factors are known to play an important aetiological role (Tiwari and Terasaki, 1985). DNA polymorphisms of the DR, DQ and DP locus antigens are associated with various autoimmune diseases (Todd et al, 1988; Thorsby et al, 1989). These molecular variations are similar to those described for IDDM, in that they are typically related to the hypervariable regions of the molecule and, thus, affect the peptide binding ability of the antigen. Based on the evidence for IDDM, population differences in the frequency of other HLA susceptibility genes are likely to be major determinants of the geographic distribution of diseases such as rheumatoid arthritis and multiple sclerosis. The epidemiological approach outlined in this review is, thus, applicable to other autoimmune diseases and will significantly contribute to our knowledge of the aetiology of these disorders. The emerging field of molecular epidemiology represents a new research approach which will lead to a better understanding of the relationships between specific risk factors and the aetiology of chronic diseases within populations and across the world. PMID- 1909860 TI - HLA class II sequences and genetic susceptibility to insulin dependent diabetes mellitus. AB - The analysis of HLA class II sequence variation in IDDM patients and controls, made possible by the PCR, has revealed that specific alleles are associated with IDDM. The HLA-DQ beta chain appears to play a role in determining genetic susceptibility and resistance, although polymorphisms in the DRB1, the DQ alpha, and the DP beta chain may also contribute. Although there is a correlation between susceptibility and the charge of DQ beta residue 57, the complex genetic epidemiology of IDDM cannot be accounted for by polymorphism at this position. As we have discussed previously (Horn et al, 1988a, 1988b; Erlich et al, 1990b), there are no unique class II sequences associated with IDDM, consistent with the view that 'normal' class II alleles confer susceptibility. Given the estimates of concordance of under 50% for monozygotic twins and approximately 15% (Tattersall and Pyke, 1972; Thomson, 1988) for HLA-identical sibs--it is not surprising that some unaffected individuals contain putative susceptibility alleles. Perhaps some environmental 'triggering' agent, such as viral infection, is required for the disease to develop in susceptible individuals. Other non-MHC-linked genes which contribute to susceptibility may account for the difference in concordance rates for monozygotic twins and for HLA-identical sibs. In the NOD (non-obese diabetic) mouse and the BB rat models for IDDM, non-MHC susceptibility loci have been identified and mapped (Colle et al, 1981; Hattori et al, 1986) but, in humans, the analysis of non-MHC candidate loci (i.e. the T cell receptor) has, thus far, failed to reveal any other susceptibility loci. In general, the HLA-linked genetic susceptibility to IDDM, as well as to other autoimmune diseases, appears to be associated with specific combinations of class II epitopes (e.g. alleles, haplotypes or genotypes) rather than with specific individual residues or epitopes. Understanding the role of these predisposing sequences will require structural analysis of the class II molecules as well as in vitro and in vivo functional studies of interactions with putative autoantigens and T cell receptors. In the meantime, DNA typing offers the potential for identifying individuals at high risk. These susceptible individuals could be monitored by immunological (e.g. anti-islet cell antibody) or by metabolic tests to detect the preclinical phase of IDDM. PMID- 1909861 TI - Non-HLA region genes in insulin dependent diabetes mellitus. AB - The focus of this chapter is on the contribution of genes outside the HLA region to insulin dependent diabetes mellitus (IDDM) susceptibility. We review laboratory evidence for such genes from published studies and also present unpublished data from our recent research. The existence of genes predisposing to IDDM in the region of the insulin (INS) gene now appears established. Association analysis has demonstrated an increased frequency of class 1 alleles of the 5' INS polymorphism in diabetics compared with controls, and a new method of analysis (AFBAC) has shown that this association is not an artefact of population stratification. Interestingly, the effect of INS region susceptibility on IDDM cannot be detected by linkage analysis, suggesting that if a genetic marker locus is close to a disease susceptibility locus, association analysis may be a more sensitive method than linkage analysis for detecting the susceptibility locus. There is no convincing evidence that genes in the T cell receptor beta chain (TCRB) or alpha chain (TCRA) regions influence predisposition to IDDM, either directly, or indirectly through interaction with HLA region genes. However, we present new evidence for interaction between TCRB and immunoglobulin heavy chain (Gm) region genes in IDDM: diabetics who are positive for the IgG2 allotype G2m(23) have significantly different frequencies of a TCRB restriction fragment length polymorphism (RFLP) than those who are negative for the allotype. Gm region genes also appear to have indirect effects on IDDM susceptibility through interaction with HLA and INS region genes: DR3/4 and non-DR3/4 diabetics have significantly different frequencies of G2m(23), and INS1/1 and non-INS1/1 diabetics also have significantly different frequencies of this allotype. To our knowledge, there are no other studies of Gm-TCRB or Gm-INS interaction in IDDM susceptibility. Evidence for Gm-HLA interaction in IDDM has been published by several other groups of investigators, however the specific phenotypic interaction effects reported have differed. Nevertheless, pooled data from three studies of Gm/HLA haplotype segregation in affected sib pairs shows significantly increased sharing of Gm haplotypes in affected pairs who share both HLA haplotypes. The biological mechanisms underlying the direct (HLA, INS) and indirect (Gm-TCRB, Gm-HLA, Gm-INS) effects of these genetic regions on IDDM susceptibility remain to be elucidated. PMID- 1909862 TI - Transgenic approaches to understanding the role of MHC genes in insulin dependent diabetes mellitus. I. Immune and non-immune mechanisms of beta cell destruction. PMID- 1909863 TI - Transgenic approaches to understanding the role of MHC genes in insulin dependent diabetes mellitus. II. The non-obese diabetic (NOD) mouse. PMID- 1909864 TI - Why is Mendelian segregation so exact? AB - The precise 1:1 segregation of Mendelian heredity is ordinarily taken for granted, yet there are numerous examples of 'cheating' genes that perpetuate themselves in the population by biasing the Mendelian process in their favor. One example is the Segregation Distortion system of Drosophila melanogaster, in which the distorting gene causes its homologous chromosome to produce a nonfunctional sperm. This system depends on three closely linked components, whose molecular basis is beginning to be understood. The system is characterized by numerous modifiers changing the degree of distortion. Mathematical theory shows that unlinked modifiers that change the degree of distortion in the direction of Mendelism always increase in the population. This provides a mechanism for removing cheaters and preserving the honesty of the Mendelian gene-shuffle. PMID- 1909865 TI - Cholesterol flux in cholesterol ester-loaded macrophages in an in vitro perfusion system. AB - Cholesterol ester-loaded J774 macrophages attached to microcarrier beads were perfused or incubated with lipoproteins in vitro. Cholesterol influx was reduced by decreasing LDL cholesterol, efflux was promoted by increasing HDL cholesterol or by adding apolipoprotein A-I/phosphatidylcholine complexes to the perfusate or incubation medium. Addition of sera obtained from patients after LDL apheresis or plasma exchange resulted in much smaller increments in cell cholesterol than pretreatment sera, due to decreased influx, but efflux was unchanged despite the reduction in HDL cholesterol by plasma exchange. These data suggest that extracorporeal cholesterol removal promotes mobilization of intracellular cholesterol ester mainly by reducing cholesterol influx. PMID- 1909866 TI - Surgical approach and sandwich radiotherapy for resectable rectal cancer: advantages and problems. AB - One hundred and twelve patients with locally advanced adenocarcinoma of the rectum have been treated with a protocol of adjuvant radiotherapy from 1981 to 1989. Radiotherapy was administered with a "sandwich" method at a dosage of 2700 cGy preoperatively and of 1800 cGy post-operatively. Only patients in stages B and C have been considered for results. Postoperative morbidity has been 16% and postoperative mortality 2.7%. Local failure was seen in 20% of patients without significant differences by stage, location, grading and operative technique. Distant metastases were seen in 31% of patients. Five-year actuarial survival was 49% and respectively 58% in stage B and 38% in stage C (P less than 0.01). Compared with a series of historical controls treated with surgery alone, the local recurrence rate was 20% vs. 26%, the distant metastases rate was 31% vs. 38% and the five-year actuarial survival rate was 49% vs. 36% (P greater than 0.01). PMID- 1909867 TI - Mechanisms of relapse for colorectal cancer: implications for intraperitoneal chemotherapy. AB - Colorectal cancer recurrence may be conceptualized as resulting from two entirely different mechanisms. First, metastases through endothelial-lined channels occur to both lymphatic and hematogenous routes. The cancers that disseminate in this fashion are metastatically inefficient. This dissemination occurs before the surgical resection of the primary cancer. Second, full thickness penetration of cancer through the bowel wall or, more frequently, intraperitoneal tumor emboli caused by the trauma of surgery result in implantation recurrence. This is seen at the resection site and on peritoneal surfaces. For the most part, this dissemination occurs at the time of surgical resection of the primary cancer. By changing the route (intraperitoneal vs. systemic) and timing (early postoperative vs. adjuvant) of chemotherapy administration this second mechanism of surgical treatment failure may be prevented. Phase II and pharmacologic studies suggest that improved survival and quality of life may occur with optimal use of early postoperative intraperitoneal chemotherapy. PMID- 1909868 TI - Role of radiation therapy in the treatment of carcinoma of the rectum. AB - Radiation therapy has assumed an integral role in the treatment of rectal carcinoma. The major role is in the surgical adjuvant setting in which the addition of radiation therapy can decrease the risk of local failure from up to 50% for stages B2 and C, to approximately 20%. The addition of sensitizing chemotherapy may add further benefit. Anal sphincter conservation is possible in another subset of patients with localized rectal carcinoma. Local excision and radiation therapy can achieve up to 90% local control, providing an attractive alternative to traditional ablative treatment. The other group of patients who benefited are those with locally advanced disease in whom a curative operative procedure cannot be performed. Radiation therapy can render greater than 50% of these patients operable and lead to about 25% long term local control. PMID- 1909869 TI - Applications of monoclonal antibodies and recombinant cytokines for the treatment of human colorectal and other carcinomas. AB - Monoclonal antibodies (MAbs) which recognize a human tumor antigen, termed tumor associated glycoprotein-72 (TAG-72), have successfully been used to localize primary as well as metastatic colorectal tumor lesions in patients. The localization of the anti-TAG-72 MAbs has also been exploited intraoperatively using a hand-held gamma probe. That procedure, termed radioimmunoguided surgery (RIGS), has identified occult tumors which were not detected using standard external imaging techniques. In another clinical trial, interferon-gamma (IFN gamma) was administered intraperitoneally to patients diagnosed with either gastrointestinal or ovarian carcinoma with secondary ascites. Analysis of the tumor cells isolated from the malignant ascites revealed a substantial increase in TAG-72 expression on the surface of tumor cells isolated from seven of eight patients. The results provide evidence that the combination of an anti-carcinoma MAb with the administration of a cytokine, such as IFN-gamma, may be an effective approach for the detection and subsequent treatment, of colorectal carcinoma. PMID- 1909870 TI - The UDP glucuronosyltransferase gene superfamily: suggested nomenclature based on evolutionary divergence. AB - A nomenclature system for the UDP glucuronosyltransferase superfamily is proposed, based on divergent evolution of the genes. A total of 26 distinct cDNAs in five mammalian species have been sequenced to date. Comparison of the deduced amino acid sequences leads to the definition of two families and a total of three subfamilies. For naming each gene, we propose that the root symbol UGT for human (Ugt for mouse), representing "UDP glucuronosyltransferase," be followed by an Arabic number denoting the family, a letter designating the subfamily, and an Arabic numeral representing the individual gene within the family or subfamily (hyphen before the Arabic number for mouse), e.g., human UGT2B1 and murine Ugt2b 1. Whereas the gene and cDNA should be italicized, the corresponding transcript, protein, and enzyme activity should not be written with lowercase letters or in italics, e.g., human or murine UGT2B1. Recent experimental evidence suggests that several exons of the UGT1 gene might be shared, indicating that distinct UGT1 transcripts and proteins may arise via alternative splicing; the gene and gene product of alternative splicing will be designated with an asterisk, e.g., UGT1*6 and UGT1*6, respectively. When an orthologous gene between species cannot be identified with certainty, as occurs in the UGT2B subfamily, we recommend sequential naming of the genes chronologically as they become characterized. We suggest that the human nomenclature system be used for species other than the mouse. We anticipate that this UGT gene nomenclature system will require updating on a regular basis. PMID- 1909871 TI - Organization of the gene encoding human lysosomal beta-galactosidase. AB - Human beta-galactosidase precursor mRNA is alternatively spliced into an abundant 2.5-kb transcript and a minor 2.0-kb species. These templates direct the synthesis of the classic lysosomal beta-D-galactosidase enzyme and of a beta galactosidase-related protein with no enzymatic activity. Mutations in the beta galactosidase gene result in the lysosomal storage disorders GM1-gangliosidosis and Morquio B syndrome. To analyze the genetic lesions underlying these syndromes we have isolated the human beta-galactosidase gene and determined its organization. The gene spans greater than 62.5 kb and contains 16 exons. Promoter activity is located on a 236-bp Pst I fragment which works in a direction independent manner. A second Pst I fragment of 851 bp located upstream from the first negatively regulates initiation of transcription. The promoter has characteristics of a housekeeping gene with GC-rich stretches and five potential SP1 transcription elements on two strands. We identified multiple cap sites of the mRNA, the major of which maps 53 bp upstream from the translation initiation codon. The portion of the human pre-mRNA undergoing alternative splicing is encoded by exons II-VII. Sequence analysis of equivalent mouse exons showed an identical genomic organization. However, translation of the corresponding differentially spliced murine transcript is interrupted in its reading frame. Thus, the mouse gene cannot encode a beta-galactosidase-related protein in a manner similar to the human counterpart. Differential expression of the murine beta-galactosidase transcript is observed in different mouse tissues. PMID- 1909872 TI - Isolation, sequence, and developmental expression of rat UGT2B2: the gene encoding a constitutive UDP glucuronosyltransferase that metabolizes etiocholanolone and androsterone. AB - The UDP glucuronosyltransferase gene UGT2B2 is constitutively expressed in rat liver, and the enzyme has been shown to conjugate glucuronic acid with various endogenous steroids, especially etiocholanolone and androsterone. We have cloned and sequenced much of the UGT2B2 gene and 5'-flanking (247 bp) and 3'-flanking (734 bp) regions. The gene contains six exons spanning about 15.3 kb. Translation begins at nucleotide 36 of exon 1 and terminates with 280 coding nucleotides into exon 6, encoding a protein of 530 amino acids (calculated Mr of the unmodified chain = 60,913). We have determined that the UGT2B2 full-length cDNA is 1,974 bp. Northern hybridization revealed that the hepatic UGT2B2 transcript is detectable 4 days before birth, becomes markedly elevated in the neonate, and is even further increased at 3 and 12 weeks of age in the liver of both male and female rats. PMID- 1909873 TI - Serum soluble CD8 molecule is a marker of CD8 T-cell activation in HIV-1 disease. AB - To characterize CD8 T-cell activation during HIV-1 infection we measured serum soluble CD8 (sCD8) levels longitudinally in seroconverters and in individuals with established HIV infection who were in different stages of illness. CD8 T cell activation occurs very early in HIV infection. Serum sCD8 levels were elevated in 91.5% of the first seropositive samples in seroconverters. Furthermore, CD8 T-cell activation persists throughout HIV infection. sCD8 predicted the occurrence of AIDS in HIV-seropositive individuals and so the addition of serum sCD8 levels to CD4 T-cell measurements increased the power in predicting the onset of AIDS. The serum level of sCD8 was particularly relevant to the prediction of subsequent CD4 T-cell fall relatively early in infection, for example, in the 3 years after seroconversion. However, later in HIV infection, for example within 2 years prior to development of AIDS, sCD8 levels were less predictive. sCD8 correlated with levels of beta 2-microglobulin and neopterin, which reflect activation of cell types other than CD8. Thus, serum sCD8 level can be a useful marker of specific CD8 T-cell activation, and is an independent predictor of prognosis in HIV infection. PMID- 1909874 TI - B-cell activation during HIV-1 infection. III. Down-regulating effect of mitogens. AB - Spontaneous in vitro production of HIV-1-specific antibodies, a hallmark of infected subjects, is often down-regulated by the addition of pokeweed mitogen. We observed that a decrease in such ongoing anti-HIV-1 antibody synthesis could also be induced in cultures from most patients by addition of phytohemagglutinin and Concanavalin A, but not by Epstein-Barr virus, a selective B-cell mitogen. In most cases, this down-regulatory effect of mitogens was evident within the first 24 h of culture. The observed mitogen-associated decrease in spontaneous antibody synthesis was prevented by treating peripheral blood mononuclear cells with agents inhibiting non-major histocompatibility complex-restricted cytotoxic activity or by adding third-party cells to the cultures. In most cases, the mitogen-induced effect was also counteracted by removal of T lymphocytes or CD8+ T-cell sub-population. These findings recall a similar phenomenon observed in normal subjects following intentional immunization, and indicate that mitogen induced down-regulation of spontaneous in vitro anti-HIV-1-antibody production most probably occurs through a lectin-dependent cytotoxic effect on activated B cells. PMID- 1909875 TI - Syncytium formation of human and non-human cells by recombinant vaccinia viruses carrying the HIV env gene and human CD4 gene. AB - We examined the ability of the various human and non-human cell lines to form syncytia upon coinfection with recombinant vaccinia viruses each carrying the HIV env and the human CD4 gene. We found that three human cell lines and one of three monkey cell lines exhibited syncytium formation, but that one human cell line, two monkey cell lines and all the rabbit and mouse cell lines examined did not. This indicated that factors other than HIV env and CD4 were participating in syncytium formation and that distribution of these factors was restricted by species and by the cell type in a species. PMID- 1909876 TI - [Recombinant DNA technology in thrombolytic therapy: tissue-type plasminogen activator]. PMID- 1909877 TI - Occult surgical glove perforations in otolaryngology-head and neck surgery. AB - With the advent of the acquired immunodeficiency syndrome crisis, it has become imperative that all surgeons minimize their risk of direct contact with the patient's body fluids. In the course of performing surgery, perforations are frequently created in surgical gloves, which often go unnoticed. This study determined the frequency with which occult glove perforations occurred in 134 consecutive head and neck surgical procedures. One thousand fifty gloves (650 gloves used in surgery, 400 unused control gloves) were analyzed for the presence of perforations large enough to permit the passage of fluid. An unrecognized glove perforation was detected in 25% of surgical cases. The duration of surgery correlated strongly and positively with the incidence of perforation. Perforation rates varied widely for specific types of procedures, and are reported for each of the five subdivisions within otolaryngology-head and neck surgery. The implications of these results are described, and recommendations for the use of protective measures, especially in reference to the use of double-gloving, are made. PMID- 1909878 TI - Enhanced isolation of MOTT on egg media of low pH. AB - The influence of alternative carbon sources, i.e. glycerol and pyruvate, and medium pH on the growth of 33 mycobacterial strains, including MOTT (n = 18), M. tuberculosis (TBC) (n = 14) and BCG, was experimentally studied. This was followed by culturing of clinical specimens (n = 4706) on three medium versions for primary isolation of mycobacteria. The decrease of medium pH below 6.5 enhanced the growth of isolated strains of M. avium complex (MAI) and M. malmoense. Pyruvate had a further beneficial effect on half of them; it was, however, inhibitory to some strains of M. malmoense, MAI and TBC as well as to BCG. In primary isolation, 74 specimens were positive for TBC and 37 for MOTT. The number of MOTT isolates of potential clinical significance was 11 on unacidified and 23 on acidified media (pH 6.2) (p less than 0.05). M. malmoense and five of 11 MAI isolates were exclusively detected on acidified media. TBC was isolated in equal frequency on all media, but it was detected on the acidified versions one to four weeks earlier in 20 of 55 (36%) specimens positive on all three media versions. The results indicated that acidified media of pH 6.2 offer enhanced growth conditions for MOTT, especially MAI and M. malmoense, without interfering with the growth of TBC. The growth enhancement obtained with pyruvate for some strains and with glycerol for some others makes it necessary to use both media versions in parallel. PMID- 1909879 TI - Resources and productivity in radiation oncology in Denmark, Finland, Iceland, Norway and Sweden during 1987. AB - Data concerning megavoltage equipment and use of megavoltage external beams in cancer management during 1987 in Denmark, Finland, Iceland, Norway, and Sweden were collected from all 37 centres serving a population of 23 million in these countries. Population per Linear Accelerator Equivalent (LAE) unit ranged from 0.30 million/LAE unit (Denmark) to 0.19 million/LAE unit (Sweden). The number of field treatments were 227,548 (Denmark), 259,917 (Finland), 10,426 (Iceland), 147,960 (Norway) and 490,126 (Sweden). The number of field treatments per million population per year ranged from 35,229 (Norway) to 58,438 (Sweden). The number of field treatments per LAE unit/year ranged from 13,192 (Denmark) to 9,546 (Norway). The fraction of cancer patients receiving megavoltage radiotherapy in 1987 out of all newly diagnosed cancer patients during 1987 was 24% in Denmark, 37% in Iceland, 25% in Norway, and 34% in Finland and Sweden. We conclude that Denmark and Norway probably did not provide adequate levels of radiotherapy for their cancer patients during 1987. PMID- 1909880 TI - Dietary regulation of cytochrome P450. PMID- 1909881 TI - Lysine-pipecolic acid metabolic relationships in microbes and mammals. PMID- 1909882 TI - Parenteral nutrition: effect on bone and mineral homeostasis. PMID- 1909883 TI - Pseudoarthrosis of the ulna in neurofibromatosis. A report of four cases. AB - Four children suffering from neurofibromatosis with ulnar pseudarthrosis and progressive reabsorption of the middle and distal thirds of the ulna are reported. None had any pain or sensory loss, but all had progressive deformity of the forearm. Instability of the elbow and wrist were present in three cases, while one case showed good stability and function. A cross-union of the ulna with the radius to produce a one-bone forearm was accomplished using screw fixation and iliac bone grafting, and a one-bone forearm was achieved in three cases. Non operative management was decided on in the patient with slow ulna reabsorption. The creation of a one-bone forearm is more likely to produce sound union, thus avoiding the need for further operations, while conservative management should be reserved for patients with a slowly progressive condition. PMID- 1909884 TI - mRNA and protein levels of the stimulatory guanine nucleotide regulatory protein Gs are lower in the testis of obese (ob/ob) mice. AB - Probing of total testis RNA with a cDNA corresponding to the alpha s subunit of the guanine nucleotide regulatory protein (G-protein) showed that levels of mRNA were markedly reduced in the ob/ob mouse compared to its +/+ control. The lowered level of mRNA resulted in lowered protein synthesis as shown by a marked decrease in both the 48,000 and 42,000 Mr peptides detected by (1) cholera toxin ribosylation, (2) immunodetection with an antibody specific for alpha s. This was not the result of overall lowered protein synthesis since the levels of alpha i2 and the beta subunits were unchanged. In the kidney there was no change in the levels of the alpha s subunit in obese membrane preparations. Lowered levels of alpha s were not correlated with changes in adenylyl cyclase activity. This suggests that in these membranes the G-protein subunit(s) are present in excess compared to the catalytic unit of adenylyl cyclase and that in the testis the G proteins may be of more importance in other signalling pathways necessary for normal gonadal development and fertility. PMID- 1909885 TI - Diarrhoeal diseases. PMID- 1909886 TI - Immunohistochemical characterisation of extracellular matrix components of salivary gland tumours. AB - Proteoglycans (PGs) were localised immunohistochemically in 52 salivary gland tumours including pleomorphic adenoma, adenoid cystic carcinoma, acinic cell carcinoma, oncocytoma, mucoepidermoid carcinoma, clear cell tumour and Warthin tumour, using antibodies raised against large PG, small PG, chondroitin 4 sulphate PG, chondroitin 6-sulphate PG, heparan sulphate PG and keratan sulphate PG. Large PGs were mainly observed in mucinous materials of extracellular matrix (ECM) and interstitial fibrous element of tumour tissues, while small PGs were located only in hyaline matrix and surrounding fibrous (capsular) connective tissues. Chondroitin 6-sulphate PG was detected in the ECM of pleomorphic adenomas and clear cell carcinomas and in pseudocystic spaces of adenoid cystic carcinomas, but only in vessel walls in non-neoplastic tissues. Keratan sulphate PG was observed to locate in mucinous material of pleomorphic adenomas, acinic cell carcinomas and clear cell carcinomas, but not in the adenoid cystic carcinomas examined, and it was also unobservable in non-neoplastic salivary gland tissues. Heparan sulphate PG was observed on the inner surfaces of true ductal spaces of adenoid cystic carcinomas and on cell surfaces of oncocytoma cells. By HPLC analysis, individual glycosaminoglycans contained in tumour tissues were compared. Chondroitin 6-sulphate PG was very rich in ECM of pleomorphic adenomas and adenoid cystic carcinomas. Pleomorphic adenomas contained relatively more low-sulphated chondroitin sulphate than adenoid cystic carcinomas and other tumours. PMID- 1909887 TI - Serum immunoglobulin (A, G, M) levels in primary bipolar affective disorders. AB - Quantitative determination of serum immunoglobulins (A, G, M) was made in patients with primary bipolar affective disorders (PBAD) and adequate control samples. Considering the modified immunoglobulin levels, the immune factors may be incriminated in the etiopathogenesis of the disease. PMID- 1909888 TI - Identification of apolipoprotein A1 and immunoglobulin as components of a serum complex that mediates activation of human sperm motility. AB - Serum is superior to other body fluids in activating the progressive motility of human spermatozoa and is used in connection with sperm separation for fertilization in vitro. The major activating capacity is localized to a macromolecular fraction, purified to homogeneity by a four-step protocol with ion exchange chromatography, chromatofocusing, exclusion FPLC (elution corresponding to a molecular mass of about 250 kDa), and Blue Sepharose chromatography (no binding but elimination of albumin). The pure protein, at a concentration of 20 70 nmol/L, activated the motility to the same extent as serum. SDS-polyacrylamide gel electrophoresis under nonreducing conditions showed one band corresponding to a molecular mass of about 180 kDa. In the presence of mercaptoethanol, two bands are obtained corresponding to 50 kDa and about 25 kDa, respectively. Without the Blue Sepharose step, the sample after reduction revealed an additional band at about 67 kDa, suggesting that the fraction is then in complex also with albumin. Amino acid sequence analysis of the Blue Sepharose eluate identified three protein chains--those of apolipoprotein A1 and immunoglobulin heavy and light chains--suggesting that the preparation is an apolipoprotein A1-immunoglobulin complex. Antiserum raised toward the pure preparation in a rabbit inhibited human sperm motility, when added directly to spermatozoa. Pretreatment of human serum with rabbit antiserum significantly reduced its ability to activate sperm motility. The sperm activating capacity of the protein complex was destroyed by heating at 100 degrees C for 5 min, suggesting that the activity was dependent on intact protein conformations. Albumin, apolipoprotein A1, and immunoglobulins by themselves had only minor effects on sperm motility.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1909889 TI - 1H NMR spectra of vertebrate [2Fe-2S] ferredoxins. Hyperfine resonances suggest different electron delocalization patterns from plant ferredoxins. AB - We report the observation of paramagnetically shifted (hyperfine) proton resonances from vertebrate mitochondrial [2Fe-2S] ferredoxins. The hyperfine signals of human, bovine, and chick [2Fe-2S] ferredoxins are described and compared with those of Anabaena 7120 vegetative ferredoxin, a plant-type [2Fe-2S] ferredoxin studied previously [Skjeldal, L., Westler, W. M., & Markley, J. L. (1990) Arch. Biochem. Biophys. 278, 482-485]. The hyperfine resonances of the three vertebrate ferredoxins were very similar to one another both in the oxidized state and in the reduced state, and slow (on the NMR scale) electron self-exchange was observed in partially reduced samples. For the oxidized vertebrate ferredoxins, hyperfine signals were observed downfield of the diamagnetic envelope from +13 to +50 ppm, and the general pattern of peaks and their anti-Curie temperature dependence are similar to those observed for the oxidized plant-type ferredoxins. For the reduced vertebrate ferredoxins, hyperfine signals were observed both upfield (-2 to -18 ppm) and downfield (+15 to +45 ppm), and all were found to exhibit Curie-type temperature dependence. This pattern and temperature dependence are distinctly different from those found with reduced plant-type ferredoxins which have signal centered around +120 ppm with Curie-type temperature dependence, assigned to cysteines which interact with Fe(III), and signals centered around +20 ppm with anti-Curie temperature dependence, assigned to cysteines which interact with Fe(II) [Dugad, L. B., La Mar, G. N., Banci, L., & Bertini, I. (1990) Biochemistry 29, 2263-2271].(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1909890 TI - Light-chain-independent binding of adaptors, AP180, and auxilin to clathrin. AB - Binding of coated vesicle assembly proteins to clathrin causes it to assemble into regular coat structures. The assembly protein fraction of bovine brain coated vesicles comprises AP180, auxilin, and HA1 and HA2 adaptors. Clathrin heavy chains, separated from their light chains, polymerize with unimpaired efficiency when assembly proteins are added. The reassembled coats were purified by sucrose gradient centrifugation and examined for composition by SDS-PAGE and immunoblotting. We found that all four major coat proteins are incorporated in the presence and absence of light chains. Moreover, each of the purified coat proteins is able to associate directly with clathrin heavy chains in preassembled cages as efficiently as with intact clathrin. We conclude that light chains are not essential for the interaction of AP180, auxilin, and HA1 and HA2 with clathrin. PMID- 1909891 TI - Conformational mobility of His-64 in the Thr-200----Ser mutant of human carbonic anhydrase II. AB - The three-dimensional structure of the Thr-200----Ser (T200S) mutant of human carbonic anhydrase II (CAII) has been determined by X-ray crystallographic methods at 2.1-A resolution. This particular mutant of CAII exhibits CO2 hydrase activity that is comparable to that of the wild-type enzyme with a 2-fold stabilization of the E.HCO3- complex and esterase activity that is 4-fold greater than that of the wild-type enzyme. The structure of the mutant enzyme reveals no significant local changes accompanying the conservative T200S substitution, but an important nonlocal structural change is evident: the side chain of catalytic residue His-64 rotates away from the active site by 105 degrees about chi 1 and apparently displaces a water molecule. The displaced water molecule is present in the wild-type enzyme; however, the electron density into which this water is built is interpretable as an alternate conformation of His-64 with 10-20% occupancy. The rate constants for proton transfer from the zinc-water ligand to His-64 and from His-64 to bulk solvent are maintained in the T200S variant; therefore, if His-64 is conformationally mobile about chi 1 and/or chi 2 during catalysis, compensatory changes in solvent configuration must sustain efficient proton transfer. PMID- 1909892 TI - Secondary structure and side-chain 1H and 13C resonance assignments of calmodulin in solution by heteronuclear multidimensional NMR spectroscopy. AB - Heteronuclear 2D and 3D NMR experiments were carried out on recombinant Drosophila calmodulin (CaM), a protein of 148 residues and with molecular mass of 16.7 kDa, that is uniformly labeled with 15N and 13C to a level of greater than 95%. Nearly complete 1H and 13C side-chain assignments for all amino acid residues are obtained by using the 3D HCCH-COSY and HCCH-TOCSY experiments that rely on large heteronuclear one-bond scalar couplings to transfer magnetization and establish through-bond connectivities. The secondary structure of this protein in solution has been elucidated by a qualitative interpretation of nuclear Overhauser effects, hydrogen exchange data, and 3JHNH alpha coupling constants. A clear correlation between the 13C alpha chemical shift and secondary structure is found. The secondary structure in the two globular domains of Drosophila CaM in solution is essentially identical with that of the X-ray crystal structure of mammalian CaM [Babu, Y., Bugg, C. E., & Cook, W.J. (1988) J. Mol. Biol. 204, 191-204], which consists of two pairs of a "helix-loop-helix" motif in each globular domain. The existence of a short antiparallel beta-sheet between the two loops in each domain has been confirmed. The eight alpha-helix segments identified from the NMR data are located at Glu-6 to Phe-19, Thr-29 to Ser-38, Glu-45 to Glu-54, Phe-65 to Lys-77, Glu-82 to Asp-93, Ala-102 to Asn-111, Asp-118 to Glu-127, and Tyr-138 to Thr-146. Although the crystal structure has a long "central helix" from Phe-65 to Phe-92 that connects the two globular domains, NMR data indicate that residues Asp-78 to Ser-81 of this central helix adopt a nonhelical conformation with considerable flexibility. PMID- 1909893 TI - Mechanism of the reaction catalyzed by mandelate racemase. 3. Asymmetry in reactions catalyzed by the H297N mutant. AB - The two preceding papers [Powers, V. M., Koo, C. W., Kenyon, G. L., Gerlt, J. A., & Kozarich, J. W. (1991) Biochemistry (first paper of three in this issue); Neidhart, D. J., Howell, P. L., Petsko, G. A., Powers, V. M., Li, R., Kenyon, G. L., & Gerlt, J. A. (1991) Biochemistry (second paper of three in this issue)] suggest that the active site of mandelate racemase (MR) contains two distinct general acid/base catalysts: Lys 166, which abstracts the alpha-proton from (S) mandelate, and His 297, which abstracts the alpha-proton from (R)-mandelate. In this paper we report on the properties of the mutant of MR in which His 297 has been converted to asparagine by site-directed mutagenesis (H297N). The structure of H297N, solved by molecular replacement at 2.2-A resolution, reveals that no conformational alterations accompany the substitution. As expected, H297N has no detectable MR activity. However, H297N catalyzes the stereospecific elimination of bromide ion from racemic p-(bromomethyl)mandelate to give p-(methyl) benzoylformate in 45% yield at a rate equal to that measured for wild-type enzyme; the unreacted p-(bromomethyl)mandelate is recovered as (R)-p (hydroxymethyl)mandelate. At pD 7.5, H297N catalyzes the stereospecific exchange of the alpha-proton of (S)- but not (R)-mandelate with D2O solvent at a rate 3.3 fold less than that observed for incorporation of solvent deuterium into (S) mandelate catalyzed by wild-type enzyme. The pD dependence of the rate of the exchange reaction catalyzed by H297N reveals a pKa of 6.4 in D2O, which is assigned to Lys 166.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1909894 TI - Characterization of maize microtubule-associated proteins, one of which is immunologically related to tau. AB - Microtubule-associated proteins (MAPs) are identified as proteins that copurify with tubulin, promote tubulin assembly, and bind to microtubules in vitro. Higher plant MAPs remain mostly unknown. One example of non-tubulin carrot proteins, which bind to neural microtubules and induce bundling, has been reported so far [Cyr, R. J., & Palewitz, B. A. (1989) Planta 177, 245-260]. Using taxol, we developed an assay where higher plant microtubules were induced to self-assemble in cytosolic extracts of maize cultured cells and were used as the native matrix to isolate putative plant MAPs. Several polypeptides with an apparent molecular masses between 170 and 32 kDa copolymerized with maize microtubules. These putative maize MAPs also coassembled with pig brain tubulin through two cycles of temperature-dependent assembly-disassembly. They were able to initiate and promote MAP-free tubulin assembly under conditions of nonefficient self-assembly and induced bundling of both plant and neural microtubules. One of these proteins, of about 83 kDa, cross-reacted with affinity-purified antibodies against rat brain tau proteins, suggesting the presence of common epitope(s) between neural tau and maize proteins. This homology might concern the tubulin binding domain, as plant and neural tubulins are highly conserved and the plant polypeptides coassembled with brain tubulin. PMID- 1909895 TI - Cytoplasmic phosphorylating domain of the mannitol-specific transport protein of the phosphoenolpyruvate-dependent phosphotransferase system in Escherichia coli: overexpression, purification, and functional complementation with the mannitol binding domain. AB - The cytoplasmic C-terminal domain, residues 348-637, and the membrane-bound N terminal domain, residues 1-347, of EIImtl have been subcloned and expressed in Escherichia coli. The N-terminal domain, IICmtl, contains the mannitol binding site, and the C-terminal domain, IIBAmtl, contains the activity-linked phosphorylation sites, His-554 and Cys-384. Overexpression of the BA domain was achieved by a translational in-frame fusion of the gene with the cro ATG start codon, downstream of the strong PR promoter of phage lambda. The domain has been purified and characterized in in vitro complementation assays. It possessed no mannitol phosphorylation activity itself but was able to restore the phosphoenolpyruvate-dependent phosphorylation activity of two EIImtl phosphorylation site mutants, lacking His-554 or Cys-384. The complementary N terminal domain was also expressed. Membranes possessing IICmtl were unable to phosphorylate mannitol at the expense of phosphoenolpyruvate. However, when the membranes were combined with the purified C-terminal domain, mannitol phosphorylation activity was restored. Mannitol transport and phosphorylation were also restored in vivo when the two plasmids encoding the N- and C-terminal domains were expressed in the same cell. These data demonstrate the existence of structurally and functionally distinct domains in EIImtl: a cytoplasmic domain with phosphorylating activity and a membrane-bound N-terminal domain which, in the presence of the cytoplasmic domain, is able to actively transport and phosphorylate mannitol. The ability to separate, overproduce, and purify structurally stable, enzymatically active domains opens the way for 3D structural studies as well as complete kinetic analysis of the activities of the individual domains and their interactions. PMID- 1909896 TI - Role of lipid transfer particle in transformation of lipophorin in insect oocytes. AB - Oocyte development in Manduca sexta involves the deposition of large amounts of lipoprotein-derived lipid. One source of this lipid is hemolymph high-density lipophorin-adult (HDLp-A) which, upon entry into the oocyte, is transformed into a lipid and apolipophorin III deficient product particle, egg very-high- density lipophorin (VHDLp-E; density = 1.24 g/ml; Kawooya et al. (1988) J. Biol. Chem. 263, 8740-8747). An in vitro model of this transformation has been established using human low-density lipoprotein (LDL) as acceptor of HDLp-A associated lipid in a reaction catalyzed by isolated M. sexta hemolymph lipid transfer particle (LTP). Facilitated vectorial net transfer of lipid from HDLp-A to LDL resulted in formation of a very-high-density lipophorin (VHDLp) product with a density and apolipoprotein content similar to that of VHDLp-E. Lipid was found to comprise 25% of the VHDLp particle mass, whereas over 50% of HDLp-A mass is lipid. Based on these observations it was hypothesized that a lipid transfer factor may be present in M. sexta oocytes and function in the transformation of HDLp-A to VHDLp E in vivo. Transfer activity was present in the buffer soluble fraction of oocyte homogenates and purification of the active material revealed a catalyst with electrophoretic and immunological properties identical to hemolymph LTP. Incubation of 125I-HDLp-A with an M. sexta oocyte homogenate resulted in transformation of the radiolabeled lipoprotein to a density corresponding to that of VHDLp-E. When the incubation media was preincubated with anti-LTP IgG this conversion was inhibited to a large extent. Inhibition was relieved, however, by addition of exogenous LTP. The results provide the first demonstration of M. sexta LTP in a tissue other than hemolymph and support the concept that LTP catalyzed lipid transfer plays an integral role in the conversion of HDLp-A to VHDLp-E in vivo. PMID- 1909897 TI - Endotoxin-induced arachidonic acid metabolism requires de novo protein synthesis and protein kinase C activation. AB - The mechanisms whereby bacterial endotoxins stimulate arachidonic acid metabolism in macrophages are uncertain. Both protein kinase C activation and de novo protein synthesis occur in macrophages in response to endotoxin. In this study we evaluated the time course and role of protein kinase C and de novo protein synthesis in endotoxin stimulated arachidonic acid metabolism in resident rat peritoneal macrophages. Thromboxane (TX) B2 was measured as the representative arachidonic acid metabolite synthesized in response to Salmonella enteritidis endotoxin, calcium ionophore A23187, or phorbol 12-myristate 13-acetate (PMA). The effect of inhibition of protein kinase C by 1-(5-isoquinolinsulfonyl)-2 methylpiperazine dihydrochloride (H-7) and staurosporine on endotoxin- and A23187 induced TXB2 synthesis was examined. The potential roles of transcriptional and translational events in endotoxin- and A23187-stimulated TXB2 synthesis were determined by utilizing the transcriptional inhibitors camptothecin (10 microM) or actinomycin D (0.08 microM), and the translational inhibitor cycloheximide (0.1 microM). Whereas, A23187 stimulated maximal TXB2 synthesis within 15 min, endotoxin showed a more prolonged time course with a 12-fold increase in TXB2 synthesis above basal levels after 3 h (P less than 0.05). PMA induced an approx. 8-fold increase above basal TXB2 levels that was blocked by inhibition of transcription with actinomycin D. H-7 (10 microM to 50 microM) inhibited endotoxin- and A23187-stimulated eicosanoid synthesis. Staurosporine (0.2 microM) produced a selective 66% inhibition of endotoxin, but not A23187-stimulated TXB2 synthesis. Endotoxin-induced TXB2 production was significantly (P less than 0.05) inhibited by staurosporine, camptothecin, actinomycin D or cycloheximide at intervals from 30 min prior to, through 60 min after endotoxin stimulation. These studies suggest a role for protein kinase C activation and de novo protein synthesis in endotoxin signal transduction events leading to increased macrophage arachidonic acid metabolism. These intracellular events are essential in sustaining the prolonged inflammatory response to endotoxin. PMID- 1909898 TI - Transformations of reconstituted high-density lipoprotein subclasses as a function of temperature or LDL concentration. AB - The objectives of this study were to determine the structural changes in defined, reconstituted high density lipoproteins (rHDL) resulting from spontaneous phospholipid depletion in the presence or absence of low-density lipoproteins (LDL), to establish the precursor-product relationships among the rHDL particles and to assess the differences in behavior of rHDL particles containing apo A-I or apo A-II. The rHDL particles were prepared by the sodium cholate dialysis method, and were incubated in buffer at 50 degrees C, or in buffer containing different concentrations of LDL at 37 degrees C, for up to 24 h. The changes in the rHDL particle distributions with time were followed by non-denaturing gradient gel electrophoresis, and the rHDL were isolated at various time points for chemical analysis. We found that rHDL particles containing apo A-I or apo A-II lose phospholipid and gain cholesterol when incubated with LDL. Increasing LDL concentrations remove increasingly larger amounts of phospholipid. With phospholipid loss the apo A-I containing particles undergo major structural rearrangements that give rise to 78 A and 106 A particles from 86 A and 94 A precursors. The 78 A products appear to be the most stable, lipid-poor species. Reconstituted HDL particles prepared with apo A-II (94 and 101 A in diameter) are more resistant to structural rearrangements than the apo A-I counterparts under similar reaction conditions. PMID- 1909899 TI - Insulin-like action of catecholamines and Ca2+ to stimulate glucose transport and GLUT4 translocation in perfused rat heart. AB - The uptake of 2-deoxyglucose by perfused rat hearts was compared to the distribution of the insulin-regulatable glucose transporter (GLUT4) in membrane preparations from the same hearts. The hearts were treated with the alpha adrenergic combination of epinephrine + propranolol, the beta-adrenergic agonist isoproterenol, high (8 mM) Ca2+ concentrations, insulin and the alpha adrenergic combination or insulin alone. Epinephrine (1 microM) + propranolol (10 microM), isoproterenol (10 microM), high Ca2+, insulin (1 microM) + epinephrine (1 microM) + propranolol (10 microM) and insulin (1 microM) each led to an increase in 2 deoxyglucose uptake and a shift in the recovery of the GLUT4 from a high-speed pellet membrane fraction (putatively intracellular) to a low-speed pellet membrane fraction (putatively sarcolemmal). There were significant correlations (r = -0.673, P less than 0.001) between the stimulation of 2-deoxyglucose uptake and the loss of GLUT4 from the intracellular membrane fraction, or the increase in the sarcolemmal fraction. The data provide evidence that the GLUT4 is translocated by agents that stimulate glucose transport in heart, and therefore this mechanism is not restricted to insulin. PMID- 1909900 TI - Pathways of oncogenesis in primary brain tumors. AB - Recent efforts have been directed at identifying and characterizing candidate tumor suppressor genes and the activities of oncogenes in primary brain tumors. The p53 gene mapping to region p13 of chromosome 17 has several characteristics as a tumor suppressor gene. The wild-type p53 protein, which is a transcriptional activator, may serve as a barrier to the progression of neoplastic processes, and alterations of p53 are involved in genesis of various cancers including astrocytomas. The NF1 gene, which is responsible for the susceptibility to neurofibromatosis type 1, has recently been isolated. This gene is assumed to play a role in the signal transduction pathway by interacting with the ras gene product. Recent observation revealed that the NF1 gene may regulate the neuronal differentiation, and the alteration in regulation of the NF1 transcript is potentially related to the progression of neuroectodermal tumors. Restriction fragment length polymorphism studies have also shown chromosomal losses associated with chromosome 9, 10 and 17. These losses of genetic material are suspected to involve loci near or at the p53 gene for chromosome 17, and neighboring the interferon genes on chromosome 9. Although no sublocalization of chromosome 10 deletions has been accomplished, all of these loci are thought to harbor tumor suppressor genes. Recent advances in oncogene research have focused on understanding the mechanisms of action of growth factors, growth factor receptors, and their substrates, particularly in glial oncogenesis. Fibroblast growth factor, epidermal growth factor, and their respective receptors are of particular interest. However, the ROS oncogene, which is expressed and rearranged in some glioma cell lines, may not be a critical factor in the development of gliomas.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1909901 TI - Thrombin activation and increased fibrinolysis in patients with chronic liver disease. AB - The respective roles of intravascular coagulation (DIC) and fibrinolysis were assessed in severe chronic liver disease by measuring thrombin-antithrombin (TAT) complexes, tissue-type plasminogen activator antigen (tPA Ag) and fibrinogen and fibrin degradation products (FgDP and FbDP respectively) in 66 patients with liver disease caused by cirrhosis (n = 34) or chronic hepatitis (n = 32) as compared to findings in a control group (n = 30). There was a significant increase of TAT complexes (P less than 0.01), tPA Ag (P less than 0.002), FDP and FbDP (P less than 0.001) in patients as compared to controls. FbDP increase was more evident in patients with cirrhosis than in those with hepatitis (P less than 0.01). Significant correlations between these parameters with some liver function tests were also demonstrated. Thus, in patients with severe liver disease, an increased thrombin activity, as demonstrated by high TAT levels; followed by hyperfibrinolysis suggest that a low grade DIC may occur. PMID- 1909902 TI - Venous thrombosis and tissue plasminogen activator release deficiency: a family study. AB - Thrombotic events are often due to fibrinolytic defects such as impaired tissue plasminogen activator (tPA) synthesis and/or release or increased plasminogen activator inhibitor (PAI) levels. In this report we describe four members of a family with a history of recurrent venous thrombosis, who demonstrated defective tPA release after dynamic tests. Two symptomatic patients and one asymptomatic individual showed absent or abnormally low tPA antigen (tPA:Ag) and activity (PA) increases after DDAVP infusion and/or 20 min of venous occlusion. In these patients PAI values were slightly higher than controls. A satisfactory tPA:Ag release was found in the fourth asymptomatic patient. All other coagulation tests were within the normal ranges. This familial defect of the fibrinolytic system seems to be inherited as an autosomal trait. PMID- 1909903 TI - Qualitative assessment of von Willebrand factor (vWF) in cirrhotics following repeated doses of desmopressin acetate. AB - Qualitative abnormalities in von Willebrand Factor (vWF) in patients with cirrhosis have been little studied with contrasting results. We used crossed immunoelectrophoresis (2-DIE) and multimeric analysis of vWF in eight patients with stable hepatic cirrhosis to evaluate abnormalities in vWF before and 1 h following intravenous administration of three doses of desmopressin acetate (0.3 micrograms/kg) given at baseline, 4 and 24 h. We thought that qualitative abnormalities might be more easily detected following desmopressin as this is known to release vWF from storage sites. There was an increased electrophoretic mobility on 2-DIE in all patients with no change following desmopressin. The multimeric analysis did not show an increase in lower molecular weight multimers, but showed a statistically significant increase in higher molecular weight multimers following desmopressin (P less than 0.02). These results suggest that the vWF of cirrhotics has an abnormal charge (not altered by release following desmopressin) which would explain the increased electrophoretic mobility on 2-DIE with a normal pattern of lower molecular weight multimers using multimeric analysis. PMID- 1909904 TI - Quality monitoring of haemapheresis platelet concentrates: sampling in EDTA helps with the standardization and improves the consistency. AB - At the North London Blood Transfusion Centre, all haemapheresis platelet concentrates (PC) are tested in duplicate by a Technicon H-1 analyser to provide accurate information on the cell separator performance and on the cellular content of packs before issue. Repeated counting on fresh samples (within 4 h) reveals spontaneous aggregation (SA), which causes inconsistency in the estimated platelet yields and invalidates the cellular indices. Preliminary work showed that sampling into EDTA eliminated SA. Further studies on the effect of EDTA were undertaken as follows: (i) using the same PCS preparations (n = 7) stored conventionally and sampled daily in tubes with and without EDTA, and (ii) using fresh V50 and CS3000 PC to assess the difference on samples routinely collected in EDTA tubes for 2 months compared to those collected without EDTA in the previous 2 months. EDTA improved concordance of duplicate counts in fresh products. The increase in platelet yield in V50 and CS3000 preparations (12-22% respectively) was associated with a concomitant decrease (60-74%) in erythrocyte contamination. The variation in leucocyte count (3-5%) was less pronounced but the percentage differential was affected. There was also a systematic increase (8 11%) in mean platelet volume (MPV) due to EDTA. In PCS preparations the EDTA induced variation in the cellular indices remained essentially in the same order (2-6%), while the MPV decreased progressively on storage. The difference in MPV can be used to assess the storage stability of various PC preparations. The implication of a double sampling technique (CPDA-1 and EDTA/CPDA-1) in the quality monitoring of haemapheresis procedures is substantial. PMID- 1909905 TI - Characteristics of platelet concentrates, with particular reference to Autopheresis C Plateletcell: correlation between dMPV and other tests for platelet function. AB - The quality of platelet concentrates (PC) collected by the Autopheresis C cell separator was assessed in two Regional Transfusion Centres taking part in a multicentre study. This study also enabled the assessment of a new simple, rapid test of platelet function and comparison with more established tests, such as aggregation to adenosine diphosphate, as a tool for the quality testing of PC. The new test, based upon the measurement of mean platelet volume using automated haematological cell analysers, is rapid and uses the same samples as those used to estimate the platelet and leucocyte content of the concentrates. The high correlation between this test and the other tests of platelet function used in the study suggests that it is an ideal tool in the quality testing of platelet concentrates. PMID- 1909906 TI - Dipyridamole potentiates the inhibition of platelet aggregation by aspirin (in human platelet rich plasma and whole blood). AB - This study investigates the influence of dipyridamole on platelet aggregation as evaluated by a single agonist or a pair of agonists in human platelet rich plasma and whole blood. Dipyridamole up to 30 microM was not found to influence the platelet aggregation of platelet rich plasma or whole blood; aspirin (100 microM), on the contrary, did inhibit platelet aggregation. The inhibition of platelet aggregation by aspirin could be reversed by using high concentrations of agonists or pairs of agonists. In this model dipyridamole inhibited platelet aggregation in both platelet rich plasma and whole blood in a dose-dependent fashion. Thromboxane A2 was less than 10% of controls in aspirin-treated PRP stimulated with low or high concentrations of collagen or with a pair of agonists. This study suggests that dipyridamole has direct antiplatelet activity in platelet rich plasma and whole blood when the cyclooxygenase pathway is blocked by aspirin. PMID- 1909907 TI - CDF/LIF selectively increases c-fos and jun-B transcripts in sympathetic neurons. AB - We recently demonstrated that the neuronal cholinergic differentiation factor (CDF) which switches the neurotransmitter phenotype of cultured sympathetic neurons from noradrenergic to cholinergic is identical to leukemia inhibitory factor (LIF). To elucidate some of the initial events leading to the phenotypic switch, the effects of CDF/LIF on the mRNA levels of several immediate early genes were examined in cultured neonatal rat sympathetic neurons. c-fos and jun-B were induced within 30 min of addition of CDF/LIF. In contrast, no effect on the expression of c-myc, fra-1, v-jun or actin mRNA was detected at this time. Thus, CDF/LIF may induce the expression of particular immediate early genes prior to its positive and negative effects on neurotransmitter and neuropeptide gene expression. PMID- 1909908 TI - Nucleotide sequences of a soybean lipoxygenase gene and the short intergenic region between an upstream lipoxygenase gene. PMID- 1909910 TI - Oxidation pathways in methylotrophs. PMID- 1909909 TI - [Presence of specific mutation of Ha-ras oncogene in skin tumors of mice induced under different experimental conditions]. AB - The mutation was revealed with substitution of A for T in the second position of the 61 Ha-ras oncogene codon in the DNA of 31 skin tumours (26 papillomas and 5 carcinomas) and in 23 mice treated with 12-O-tetradecanoyl phorbol-13-acetate (TPA). Part of these mice were F progeny (n-6) and F progeny (n-4) following DMBA administration during pregnancy, another part F progeny (n-5) following ENU action on males prior to mating, the rest mice (n-3) did not undergo additional actions. The mutation under study was revealed only in 3 out of 5 papillomas and in all 5 carcinomas of mice subjected to DMBA administration during pregnancy. PMID- 1909911 TI - Regulation of oxidation and assimilation of one-carbon compounds in methylotrophic bacteria. PMID- 1909912 TI - Growth yields, productivities, and maintenance energies of methylotrophs. PMID- 1909913 TI - Mixed substrates and mixed cultures. PMID- 1909914 TI - Single cell protein production from C1 compounds. PMID- 1909915 TI - Enzymes of industrial potential from methylotrophs. PMID- 1909916 TI - Production of useful chemicals by methylotrophs. PMID- 1909917 TI - Molecular genetics of methylotrophic bacteria. PMID- 1909918 TI - Taxonomy of methylotrophic bacteria. PMID- 1909919 TI - Ecology of methylotrophic bacteria. PMID- 1909920 TI - Ultrastructure of methylotrophic microorganisms. PMID- 1909921 TI - Assimilation of carbon by methylotrophs. PMID- 1909922 TI - Extended inpatient treatment of a refractory heroin addict: a multidisciplinary approach to patients with a dual diagnosis. AB - Chemically dependent patients may also have a psychiatric problem (e.g., thought disorder, affective disturbance, character pathology). They may suffer as well from concomitant neurological deficits. Consequently, such patients are difficult to treat, and they tend to relapse after achieving sobriety in a short-term treatment program. Traditional chemical dependency programs thus may run the risk of oversimplifying the needs of these refractory patients. The authors present a clinical case to illustrate how an in-depth assessment and extended inpatient care by a multidisciplinary treatment team can achieve more lasting success with refractory dual-diagnosis patients. PMID- 1909923 TI - Effects of haloperidol administration on in vivo extracellular dopamine in striatum and prefrontal cortex after partial dopamine lesions. AB - The effects of haloperidol on striatal and prefrontal cortical extracellular fluid dopamine (DA) concentrations were examined in sham-operated control rats and in rats which had received partial lesions of their dopamine systems. In control rats haloperidol administration produced increases in extracellular fluid DA concentrations in both the striatum and prefrontal cortex. However, in rats which had been partially lesioned with intracerebroventricular 6-hydroxydopamine, haloperidol produced an increase in extracellular fluid DA concentration in the prefrontal cortex but failed to alter striatal DA release. These data suggest that nigrostriatal and mesocortical DA neurons have different response capabilities following partial DA lesions. PMID- 1909924 TI - The effects of dietary concentrations of minerals, source of protein, amino acids and antibiotics on the growth of and digestibility of amino acids by broiler chickens. AB - 1. The effects of dietary calcium, available phosphorus, amino acid and antibiotic supplements on the digestibilities of amino acids and growth of broiler chickens were investigated in two experiments. 2. The performance of chickens fed on diets containing high concentrations of calcium and available phosphorus was poorer with meat meal-based diets than with soyabean-based diets. Methionine supplementation improved the performance of chickens fed meat meal based diets. 3. A high dietary content of calcium (25.9 vs 11.8 g/kg) reduced chick performance and the digestibility of glutamic acid, leucine and phenylalanine but increased the digestibility of lysine and histidine. 4. High dietary contents of calcium and available phosphorus (24.3 and 13.0 vs 11.8 and 4.0 g/kg) reduced chick performance and the digestibilities of most amino acids. 5. Antibiotic supplementation did not improve the performance of chickens, but increased the digestibilities of most amino acids in chickens fed on diets with a high calcium or high calcium and available phosphorus contents. 6. It was concluded that excess dietary calcium alone, or calcium and phosphorus together, reduced chick performance and the digestibilities of most amino acids. Growing chickens tolerated excess dietary calcium and available phosphorus better in well balanced amino acid diets, such as soyabean meal or methionine-supplemented meat meal diets, than in poorly balanced amino acid diets, such as unsupplemented meat meal diets. PMID- 1909925 TI - Optimum threonine requirement of laying hens. AB - 1. One experiment was conducted with medium weight laying hens to determine their threonine requirement between 28-38 weeks. 2. Two threonine-limiting diets of identical protein quality (summit-dilution) were used and, by dilution, ten protein contents were produced supplying 2.7 to 5.4 g total threonine/kg diet. The diet with the lowest protein was also supplemented with synthetic L threonine. Each diet was fed to 5 groups of 24 laying hens. 3. The daily threonine requirement of the individual laying hens was estimated by direct methods to be 8.7 mg/g egg output plus 43.49 mg/kg body weight for this experiment. Calculated optimum intakes of threonine for various ratios of costs of input to value of output are tabulated. For example, for a flock of medium weight laying hens producing an average of 50 g daily egg mass, the optimum threonine intake (mg/hen d) varied between 700 and 710 for cost ratios (k-values) varying between 0.002 and 0.001. PMID- 1909927 TI - Linear Programming for optimization of nurse scheduling. PMID- 1909926 TI - Comparative solubility study of human dental enamel, dentin, and hydroxyapatite. AB - The solubility properties of hydroxyapatite (HA) are compared with those of human dental enamel and dentin. The apatites used in this study were equilibrated with dilute phosphoric acid solutions in CO2-containing atmospheres. The experimental results are interpreted in terms of solubility models which consider the biological materials as either HA or carbonatoapatites. Both in the HA and the dental mineral systems, the results are consistent with the precipitation of another carbonate-containing apatitic phase during equilibration. However, although the chemical behavior of the HA systems is in very good agreement with predictions based on the solubility models, the results with the bioapatites are not; this inconsistency is more marked for dentin than for enamel but in both cases the results clearly indicate the inadequacy of assuming for these dental apatites the stoichiometry of HA. The models and the experimental results show that, in principle, it is possible to define the two dental minerals in terms of respective solubility product constants, if independent information is attained on the stoichiometry of these bioapatites. PMID- 1909928 TI - Calcaneonavicular bar resection. AB - 1. Results of resection of calcaneonavicular bars in 16 feet are reported. Satisfactory results were obtained in 75% (12 of 16 feet). 2. Inadequate resection of the bar correlated with regrowth (recurrence) of the bar. 3. Good postoperative subtalar joint range of motion correlated with good results. 4. Degeneration in the rearfoot correlated with poor results. 5. Resecting the bar in the presence of another coalition yielded a poor result. 6. Resection of completely ossified bars versus incompletely ossified bars yielded no difference in results as long as no degeneration in the rearfoot was present. PMID- 1909929 TI - Effects of high-fat diet on the patterns of prostatic cancer induced in rats by N nitrosobis(2-oxopropyl)amine and testosterone. AB - Controversial views exist on the link between prostatic cancer and consumption of high-fat (HF) diet. This topic was examined in experimental prostatic cancer induced in rats by N-nitrosobis(2-oxopropyl)amine (BOP). Groups of Wistar-derived MRC rats were fed a semipurified diet containing either 5% (low fat = LF) or 24.6% (HF) corn oil for life, beginning after weaning. In the short-term study, treatment with testosterone significantly increased the rate of cellular DNA synthesis (as determined by autoradiographs after tritiated thymidine injection) that was not influenced by the level of dietary fat. HF diet alone depressed the rate significantly in the dorsal lobe only. There was a significant increase in the plasma level of estradiol, a decrease in the level of luteinizing hormone, but no changes in the level of follicle-stimulating hormone (FSH) in rats treated with testosterone, with no differences between the HF and LF groups. However, HF in the absence of testosterone depressed the serum FSH level. In the carcinogenicity experiment, all rats fed HF or LF diet developed prostatic cancers (mostly adenocarcinomas). The incidence, however, was significantly higher in testosterone-treated rats. Dietary fat did not influence the incidence, histological patterns, or anatomical distribution of tumors, and there were no differences in the parameters between the HF- and LF-fed groups. Long-term administration of testosterone significantly lowered serum levels of luteinizing hormone but did not change the FSH level and affected estradiol levels to a variable extent. These values were not influenced by dietary fat. However, in the HF-BOP group, significantly higher levels of FSH were found compared with the values in the LF-BOP group. We concluded that (a) under the described experimental conditions, dietary fat, fed ad libitum, does not influence the patterns of prostatic cancer induced in rats by BOP; (b) testosterone alters the serum levels of estradiol and luteinizing hormone; and (c) both testosterone and estradiol could be involved in carcinogenesis. PMID- 1909930 TI - Inhibition by 2,6-dithiopurine and thiopurinol of binding of a benzo(a)pyrene diol epoxide to DNA in mouse epidermis and of the initiation phase of two-stage tumorigenesis. AB - The chemotherapeutic agent 6-mercaptopurine was previously shown to inhibit the binding of 7r,8t-dihydroxy-9,10t-oxy-7,8,9,10-tetrahydro-benzo(a) pyrene (BPDE-I) to DNA in Chinese hamster ovary cells. Two compounds related to 6-mercaptopurine, 2,6-dithiopurine (DTP) and thiopurinol (TP), have been tested for inhibition of the binding of BPDE-I to epidermal DNA in mouse skin. Doses of test compound (0.2 20 mumol) or solvent control were applied to the shaved backs of female SENCAR mice. Fifteen min later, 200 nmol [3H]BPDE-I were applied to the same area and 3 h later the mice were sacrificed and epidermal DNA was purified and adduct formation was quantitated radiometrically. At the highest doses studied, DTP and TP inhibited DNA binding by 90 and greater than 80%, respectively. The dose necessary to inhibit DNA binding by 50% was about 0.8 mumol for DTP and about 2 mumol for TP. To test whether this protective effect was long-lasting, the time between application of purinethiol and [3H]BPDE-I was systematically increased. Although the level of protection was decreased by increasing the time between applications, both compounds inhibited binding 50-60% even after 24-48 h. A radioactive compound tentatively identified as a TP-BPDE-I adduct could be recovered from epidermal homogenates following topical application of TP and BPDE I. We used a standard two-stage initiation-promotion protocol to test the effects of these compounds on mouse skin carcinogenesis. Mice were treated with 0, 1, or 10 mumol of either TP or DTP, and 15 min later were treated with an initiating dose of BPDE-I (200 nmol). Twice weekly promotion with 12-O-tetradecanoylphorbol 13-acetate was begun 2 weeks later and continued for 23 weeks. A dose-dependent inhibition of tumor incidence and multiplicity was noted with both compounds. Treatment of skin with 10 mumol of DTP prior to initiation lowered the number of papillomas per mouse by greater than 90% compared to solvent controls; a 10-fold lower dose resulted in about 50% inhibition. The 10-mumol dose of TP resulted in about 50% inhibition. Mice were examined for 50 weeks for the presence of squamous cell carcinomas. Compared to the positive control group, 10 mumol DTP inhibited carcinoma incidence and lowered the total number of carcinomas by 90 95%. Treatment with 10 mumol TP had no significant effect on carcinoma incidence, and only slightly lowered the total number of carcinomas. PMID- 1909931 TI - Role of ultraviolet radiation in the induction of melanocytic tumors in hairless mice following 7,12-dimethylbenz(a)anthracene application and ultraviolet irradiation. AB - We examined the role of UVR (UV radiation) (UVA, 320-400 nm; UVB, 290-320 nm; and the combination of UVA and UVB) as a promoter in the induction of cutaneous melanoma. One hundred and seventy hairless mice (Skh-hr2), 6-8 weeks old, were treated in 8 groups: group I, DMBA [7,12-dimethylbenz(a)anthracene] plus UVA; group II, DMBA plus UVA plus UVB; group III, DMBA plus UVB; group IV, DMBA; group V, UVA; group VI, UVA plus UVB; group VII, UVB; group VIII, control. DMBA (0.5% solution) was applied once to promote the formation of dermal melanocytic nevus like lesions while UVR treatments were conducted 3 times/week for 30 weeks. The mice were examined periodically for the development of multiple pigmented lesions, papillomas, squamous cell carcinomas, melanomas, and lymphomas. Treatment with DMBA plus UVA, DMBA plus UVB, and DMBA plus UVA plus UVB stimulated the development of multiple pigmented nevus-like lesions (85-100%) in mice of groups I, II, III, and IV. Upon necroscopy, 27-33% of animals in groups I, II, and III receiving UVR treatments developed clinically and histologically characterized melanomas. Treatment with DMBA alone did not produce melanomas. DMBA-treated animals in groups I, II, and III which received UVR treatments also developed lymphomas (21-50%). Animals treated with DMBA alone or those that received UVB or the combination of UVB plus UVA (without DMBA) developed only papillomas and squamous cell carcinomas (25-47%). Skin tumors were analyzed for the presence of point mutations in the ras gene. Polymerase chain reaction amplification of DNA and selective oligonucleotide hybridization revealed mutations in the 61st codon of the N-ras gene in the precursor nevus-like lesions and melanoma samples studied. This study suggests that UVR (both UVA and UVB) plays a role as a promoter in the stimulation of melanoma and lymphoma development in hairless mice. PMID- 1909933 TI - CD4-CD8- splenic T cells from Lewis rats recovered from experimental autoimmune encephalomyelitis respond to encephalitogenic T cells that mediate this disorder. AB - We previously demonstrated that encephalitogenic CD4+ T lymphocytes from the long term cultured line S1, specific for myelin basic protein, induce a CD8+ T cell population in vivo that protects naive Lewis rats against experimental autoimmune encephalomyelitis caused by S1 cells. In order to determine the contribution of individual T cell population in the development of induced resistance, we have analyzed the in vitro proliferative capacity of phenotypically distinct T cell populations isolated from S1-immunized rats. We found that both CD8+ and CD8-CD4- T cells show striking proliferative responses when stimulated with S1 cells, whereas CD4+ T cells show only minimal responses. In addition, a significant proportion of the CD8-CD4- cells, after stimulated by S1 cells, became CD8+ and had a strong cytolytic activity toward S1 cells. These results suggest a contribution of double-negative splenic T cells in the regulatory circuit associated with autoimmune encephalomyelitis. PMID- 1909932 TI - A Mr 46,000 human milk fat globule protein that is highly expressed in human breast tumors contains factor VIII-like domains. AB - The human milk fat globule has proved to be a good source of antigenic material for production of antibodies against surface components of breast epithelial cells. Monoclonal antibodies against one of the major components of the human milk fat globule, which identify a glycoprotein with an apparent molecular weight of 46,000, have been found to be useful for both breast cancer diagnosis and therapy. In order to characterize this Mr 46,000 glycoprotein, specific monoclonal antibodies were used to select complementary DNAs from a lambda gt11 expression library from lactating breast. The largest complementary DNA insert (BA46-1) was 1270 base pairs and encoded 217 amino acids. A single 2.2-kilobase RNA was specifically detected in a variety of carcinoma cell lines, using this complementary DNA probe, and it was overexpressed in some carcinoma lines. The mRNA levels correlated with the level of expression of the antigen in these cell lines as detected by Western blot analysis. Sequence analysis revealed strong homology of the Mr 46,000 glycoprotein with serum factors VIII and V, in the region implicated in phospholipid binding. PMID- 1909935 TI - Inhibitory effects of catechol derivatives on arachidonic acid-induced aggregation of rabbit platelets. AB - Pyrocatechol and other non-substituted dihydric phenols, which have strong redox power, inhibited arachidonic acid-induced aggregation of rabbit platelets at much lower concentrations than those at which these phenols inhibited stable prostaglandin endoperoxide, U46619-induced aggregation. Among non-substituted dihydric phenols, pyrocatechol was most potent. In order to clarify the physicochemical properties of the phenolic compounds which control the inhibitory potencies of dihydric phenols, we observed the inhibitory effects of 3- and 4 substituents of pyrocatechol on arachidonic acid-induced platelet aggregation. Among seven derivatives tested, the inhibitory effect of 4-C6H5-substituent was strongest and 4-COOH-substituent was weakest. Inhibitory effects of the catechol derivatives were well correlated with the quotients of their hydrophobicities and oxidation-reduction potentials. Inhibitory effects of hydroquinone and resorcinol were also on the same correlation line. These results suggest that the inhibitory effects of catechol derivatives and other dihydric phenols are controlled by two physicochemical properties: oxidation-reduction potential and hydrophobicity. PMID- 1909934 TI - Extracellular matrix components of the mouse thymic microenvironment. II. In vitro modulation of basement membrane proteins by interferon-gamma: relationship with thymic epithelial cell proliferation. AB - We studied the effects of recombinant interferon-gamma (IFN-gamma) on some aspects of the physiology of two murine thymic epithelial cell (TEC) lines. Besides the expected induction of MHC class II antigens, this lymphokine was able to modulate the extracellular matrix (ECM) expression by growing TEC, as well as modulate their adhesion and proliferation patterns. As regards the influence of rIFN-gamma on ECM expression, we observed that when applied in very low doses, it promoted an increase in the amounts of basement membrane proteins, mainly fibronectin. In contrast, relatively high doses of this lymphokine (10(1) to 10(2) IU/ml) induced the opposite effect. Interestingly, both the stimulatory and the blocking effects of IFN-gamma on ECM expression were paralleled by equivalent modulation of cell proliferation, in both mouse and rat TEC lines. It should be pointed out that all these effects could be significantly abrogated by an anti IFN-gamma monoclonal antibody. Searching for a putative mechanism that could be involved in the modulation of TEC proliferation by IFN-gamma, we observed a clear cut positive correlation between cell adhesion and proliferation of TEC growing onto ECM-containing substrata produced following IFN-gamma treatment. The bulk of the data presented herein suggests that IFN-gamma may play a relevant role in TEC physiology and ontogeny, not only by inducing MHC class II antigen expression but also by regulating TEC growth via the control of extracellular matrix production by these cells. PMID- 1909936 TI - Metabolism of benzo[a]pyrene and benzo[a]pyrene-7,8-dihydrodiol in human mammary epithelial cells: feedback inhibition by 7-hydroxybenzo[a]pyrene. AB - The metabolism of benzo[a]pyrene (B[a]P) and (-)-transbenzo[a]pyrene-7,8 dihydrodiol (B[a]P-diol) was compared in human mammary epithelial cells (HMEC) grown in serum-free medium, MCDB-170. Conversion of B[a]P-diol to the carcinogen (+)-benzo[a]pyrene-7,8-dihydroxy-9,10-epoxide (BPDE), as measured by analysis of their tetraol hydrolysis products, occurred much more efficiently in cultures incubated with [3H]B[a]P-diol than in cultures incubated with [3H]B[a]P. In cultures pretreated with unlabeled B[a]P (24 h, 400 nM), the conversion of [3H] B[a]P-diol to [3H]tetraols is inhibited 49%, while the conversion of [3H]B[a]P to [3H]B[a]P-diol- is not affected. These observations led to the identification of a major B[a]P-derived metabolite as 7-hydroxybenzo[a]pyrene (B[a]P-7-ol), which was found to be an extremely potent and selective inhibitor of the conversion of B[a]P-diol to BPDE, with a KI estimated at 3-12 nM. Thus B[a]P activation in HMEC appears to be significantly limited by a feedback inhibition pathway induced by B[a]P-7-ol. The potency and selectivity of the B[a]P-7-ol-induced inhibition suggests that the diol to diolepoxide conversion is affected by a selective oxygenase in HMEC, rather than a non-enzymatic, peroxy radical-induced mechanism. B[a]P-7-ol should prove to be a valuable tool in the study of B[a]P carcinogenesis. PMID- 1909937 TI - Formation and persistence of benzo[a]pyrene--DNA adducts in different tissues of C57BL/10 and DBA/2 mice. AB - Synchronous fluorescence spectrophotometry (SFS) developed to study benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE)--DNA adducts was used to measure the formation and disappearance of DNA adducts in the lung, liver, kidney, spleen and small intestine of genetically responsive C57BL/10 (B10) and nonresponsive DBA/2 (D2) mice. After single stomach intubation of 100 mg/kg of benzo[a]pyrene (B[a]P) in both strains, binding of BPDE to DNA reached a peak 48 h after treatment. However, the levels of binding in the lung, liver, kidney and spleen were higher in D2 than in B10 mice. In contrast to this, in the small intestine the higher level of BPDE binding was found in B10 mice and reached its maximum 24 h earlier. Thereafter a very rapid drop in the level of BPDE--DNA adducts to a value of approximately 50% after 48 h was observed in this tissue. In the other tissues of the B10 mice the rate of adducts removal was slower, but by 14 days after treatment 90-100% of adducts were removed. In the D2 mice up to the 4th day after treatment the rates of removal of the BPDE--DNA adducts were similar to that of the B10 mice. Thereafter the level of bound hydrocarbon decreased at a slower rate. During the whole period after B[a]P treatment distinct differences between organs in the amount of BPDE--DNA adducts were observed. In D2 mice the highest level of binding was found in the spleen followed by the lung, kidney, liver and small intestine. In B10 mice the highest level of binding was observed in the DNA of small intestine. The data suggest that the decreased rate of B[a]P metabolism in D2 mice may be at least in some tissues the reason of higher binding of BPDE- DNA adducts in comparison with B10 mice. PMID- 1909938 TI - Constitutively elevated levels of ornithine and polyamines in mouse epidermal papillomas. AB - Epidermal papillomas were induced in CD-1 mice by a single topical application of 7,12-dimethylbenzanthracene (DMBA) followed by twice weekly applications of 12-O tetradecanoyl-phorbol-13-acetate (TPA) in acetone. Control groups consisted of mice treated singly or chronically with acetone or TPA. TPA induced a rapid, yet transient 500- to 1000-fold increase in ornithine decarboxylase (ODC) activity which resulted in a 2- to 8.4-fold elevation of putrescine in both singly or chronically TPA-treated mouse epidermis 4-6 h after its application. After 24 h, levels of spermidine, but not spermine, were also elevated. The ODC and arginase activities in the 11 individual papillomas studied averaged 400- and 26-fold higher respectively than basal levels in epidermis. The activity of ODC in most papillomas, unlike ODC in epidermis, could be stimulated by guanosine 5' triphosphate (GTP). Putrescine and spermidine levels in papillomas, especially those exhibiting highly GTP-stimulated ODC, were substantially higher compared to either normal or TPA-treated epidermis. Although epidermis contains a relatively high ornithine content, its level is even further elevated in papillomas, in some cases as much as 70-fold. The consequences of the constitutively elevated polyamine levels in papillomas caused by the loss of control over the normally tightly regulated polyamine biosynthetic pathway are not known, but could be important in regulating the balance between proliferation and differentiation in this self-renewing epithelial tissue. PMID- 1909939 TI - Differential locus sensitivity to mutation induction by ionizing radiations of different LETs in Chinese hamster ovary K1 cells. AB - Mutation induction after exposures to 250 kVp X-rays, alpha-particles from the radon daughter 212Bi, and fission-spectrum neutrons from the JANUS reactor was studied in Chinese hamster ovary (CHO) K1 cells and in CHO-10T5, a K1 derivative containing the bacterial gene xanthine-guanine phosphoribosyl transferase (gpt). Mutation induction was analyzed at three genetic loci: the gpt locus, the hypoxanthine-guanine phosphoribosyl transferase (hprt) locus, and the thymidine kinase (tk) locus. After X-irradiation, mutants were induced at the tk loci at approximately 8-9 times the rate of mutant induction at the hprt locus, and the rate of mutant induction at the gpt locus was 8-10 times greater than that at the hprt locus. Neutron and alpha-radiation were more effective mutagenic agents. Mutant frequencies were approximately 4- to 6-fold higher than for X-rays at the hprt and gpt loci and greater than 12-fold greater than X-rays at the tk locus. The greater sensitivity of the tk locus to mutation induction by ionizing radiation (especially neutron and alpha-particle radiation) compared to the hprt locus is likely to be due to the recovery of an additional class of mutants, possibly ones containing larger-sized mutational events. Approximately half of the X-ray-induced tk-1- mutants were small-colony mutants, and 75% of the alpha- and neutron-induced tk-1- mutants were small-colony mutants. The increase in the proportion of small-colony mutants seen with increasing radiation linear energy transfer (LET) suggests that the radiation quality influenced the type of mutation recovered at this locus. There is probably a different reason for the hypersensitivity of the gpt locus because the frequency of gpt mutants, compared to the hprt locus, was independent of radiation quality. Therefore, the LET dependence of mutant induction is gene specific and not necessarily related to the size of deletion recoverable. PMID- 1909940 TI - Lambda light chain myeloma with pleural involvement. AB - A case is reported of lambda light chain multiple myeloma complicated by a myelomatous pleural effusion. Pleural effusions are uncommon in multiple myeloma, and most are secondary to nonmalignant causes. The clinical characteristics, natural history and pathophysiology of myelomatous pleural effusions are reviewed. PMID- 1909941 TI - The "ladder light chain" or "pseudo-oligoclonal" pattern in urinary immunofixation electrophoresis (IFE) studies: a distinctive IFE pattern and an explanatory hypothesis relating it to free polyclonal light chains. AB - I previously reported the occurrence of a pattern of multiple, equally spaced, low-concentration light chain bands in urine in immunofixation electrophoresis (IFE) studies (Clin Chem 1990;36:1526-7). Although the pattern varies somewhat among patients with regard to the number of bands, light chain type, and concentration, it is relatively invariant with regard to the location and spacing of three prominent kappa bands. The regular spacing of these urinary light chain bands imparts a "ladder rung" or "pseudo-oligoclonal" appearance. High resolution, two-dimensional electrophoresis of these urine specimens reveals a regularly spaced, isomassic, restricted zonal distribution in the light chain region. These findings may be explained as the results of expression of superfamilies of related, polyclonal, free light chains, which co-migrate because of the limited variety of amino acid substitutions allowed by recombination constraints on light chain genes. This urinary IFE phenomenon is called the ladder light chain (LLC) pattern or pseudo-oligoclonal free light chain pattern to avoid implications of origin from specific clonal proliferation. PMID- 1909942 TI - Restricted electrophoretic heterogeneity of immunoglobulin light chains in urine: a cause for confusion with Bence Jones protein. AB - The detection of Bence Jones protein, an important part of the investigation of suspected myeloma, is most commonly done by agarose or cellulose nitrate electrophoresis followed by immunofixation. Bence Jones protein is recognized as single or multiple bands of one type of light chain. Unfortunately, improvements in sensitivity of these techniques (use of high-affinity antisera and higher resolution electrophoresis) frequently allow detection of multiple light chain bands in the urine of patients who do not have a B-cell dyscrasia. The bands are usually kappa, although they may be accompanied by lambda bands. This pattern may lead to the misdiagnosis of Bence Jones protein and oligoclonal light chain production in patients. Here we show that this pattern is produced by polyclonal light chains; it is present in the urine of all patients with a tubular proteinuria of any etiology and may be induced in healthy individuals by blocking their renal tubular protein reabsorption. Polyclonal light chains separate into monomers and dimers on sodium dodecyl sulfate-polyacrylamide gel electrophoresis and into four major bands with many minor bands by isoelectric focusing. This difference in charge and possibly size results in the banding pattern seen on good-quality electrophoresis and immunofixation. PMID- 1909943 TI - [Energy metabolism of ALS patients under mechanical ventilation and tube feeding]. AB - We studied the energy metabolism of ALS patients under mechanical ventilation and tube feeding. Gas exchanges (O2 and CO2 content in expiratory and inspiratory gas) were measured all day long by DELTATRAC (Datex, Finland) in 11 ALS patients, and energy metabolism during 24 hours was calculated according to the next formula; 5.67 VO2 + 1.60 VCO2-2.17 UN (VO2; O2 consumption l/min, VCO2; CO2 production l/min, UN; urea nitrogen excretion in urine g/day). All patients were clinically stable under continuous mechanical ventilation and tube feeding, and did not have any infection such as pneumonia. The patients were 23-70 years old (mean 49.3), and had total clinical courses of 3-12 years (mean 7.1), and 2-8 year-long courses under mechanical ventilation (mean 4.6). They were classified into the next 3 groups: group I; totally locked-in state (2 patients), group II; complete tetraplegia (6 patients), group III; incomplete tetraparesis (3 patients). Basal metabolic rate (BMR) of each patient was also calculated from Harris-Benedict's formula; male = 66.47 + 13.75W + 5.0H - 6.76A, female = 665.10 + 0.567W + 1.85H - 4.68A (W; weight kg, H; height cm, A; body surface area m2). And the changes of the body weight by month were examined retrospectively in 26 ALS patients with at least 2 year-duration under mechanical ventilation, which include the previous 11 patients. The calorie consumption of 24 hours were 783.3 kcal (group I), 875.3 (group II), 974.9 (group III), which were all lower than BMR (I; -26.8%, II; -17.6%, III; -11.3%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1909944 TI - Pulmonary vasodilatation and augmentation of right ventricular function following terbutaline infusion in severe chronic pulmonary disease. AB - Twenty patients with a median age of 61 years and a median forced expired volume in 1 s (FEV1) after bronchodilating therapy of 0.55 l were studied in order to measure the effect of intravenous terbutaline on bronchial tone, cardiac function, pulmonary haemodynamics, gas exchange, and oxygen transport capacity during rest and in 10 patients during exercise. Terbutaline infusion during rest resulted in an increase in heart rate from 84 to 103 beats min-1 (P less than 0.01), a decrease in mean systemic arterial pressure from 95 to 80 mmHg (P less than 0.02), an unchanged mean pulmonary arterial pressure (18 mmHg), an increase in cardiac index from 2.89 to 3.86 l min-1 m-2 (P less than 0.01), an increase in right ventricular ejection fraction from 45 to 53% (P less than 0.01), an increase in left ventricular ejection fraction from 63 to 67% (NS), an unchanged arterial oxygen tension, and an increase in calculated oxygen delivery from 533 to 638 ml O2 min-1 m-2 (P less than 0.01). During exercise terbutaline infusion resulted in an increase in heart rate from 108 to 120 beats min-1 (P less than 0.05), a decrease in mean systemic arterial pressure from 117 to 106 mmHg (P less than 0.01), a decrease in mean pulmonary arterial pressure from 29 to 22 mmHg (P less than 0.01), an increase in cardiac index from 4.53 to 4.64 min-1 m-2 (NS), an unchanged arterial oxygen tension, and an increase in the calculated oxygen delivery from 834 to 856 ml O2 min-1 m-2 (NS). It was concluded that terbutaline augments right ventricular function: increases right ventricular ejection fraction and decreases right ventricular end-diastolic volume, and further decreases pulmonary vascular resistance without decreasing arterial oxygen tension, and increases oxygen delivery in patients with chronic pulmonary disease during rest and exercise. PMID- 1909945 TI - Changes in carbohydrate metabolism during 30 months on Norplant. AB - During a 30-month period, changes in carbohydrate metabolism (measured by oral glucose tolerance test) were studied in 20 Norplant acceptors. Changes were first observed one month after Norplant insertion and peaked between 12-18 months. The area under the glucose curve rose by 12.3% and 40.5% one and 12 months post insertion, respectively. At 18, 24 and 30 months the rise was, respectively, 41.9%, 40% and 38.6%. Although the changes under the insulin curves were similar, the increase at one month was doubled (25.7%). Only fasting insulin values showed very slight and insignificant changes during the 30-month period. All the changes were, however, within the normal limits for healthy women. We conclude that although Norplant induces changes in carbohydrate metabolism, these changes remain within normal limits, peak at 12 months and either remain the same or decrease with time. PMID- 1909946 TI - Effect of human recombinant erythropoietin on dialysis efficiency in CAPD. PMID- 1909947 TI - Orthoclone OKT3 and cardiac transplantation: an overview. PMID- 1909948 TI - Low serum levels of alpha-interferon, gamma-interferon, and interleukin-2 in alcoholic cirrhosis. AB - The existence of cellular immune deficit in alcoholic cirrhosis, together with the role of alpha- and gamma-interferon and interleukin-2 in the immune system, led us to compare serum levels of these immune system mediators in a group of 40 patients with alcoholic cirrhosis classified according to Child-Pugh's grade of severity of liver disease and 23 healthy volunteers. Serum levels of alpha-IFN, gamma-IFN, and IL-2 were significantly depressed in alcoholic cirrhotics, with no significant differences between the different degrees of hepatic damage. The results suggest a profound alteration in the immune system of alcoholic cirrhotics, which may contribute to the development of the disease and the accompanying immune system deficit. PMID- 1909949 TI - [The vasomotor effects of nitrogen oxide administered into the structures of the ventrolateral area of the medulla oblongata in the cat]. PMID- 1909950 TI - [The stimulation of DNA repair in workers in contact with cadmium chloride by vitamins used as antimutagens]. PMID- 1909952 TI - Patterns of epithelial expression of Fos protein suggest important role in the transition from viable to cornified cell during keratinization. AB - An antibody directed against the DNA-binding region of c-fos was used to localize the distribution of cells positive for Fos protein in epithelial tissues. The antibody consistently bound to the nuclei of epithelial cells in the late stages of differentiation, just prior to cornification. The epidermis, palate, buccal mucosa, gingiva, tongue, forestomach and vagina in estrus all produced this type of labelling, suggesting a burst of expression immediately before cell death and cornification. The differentiating cells of the hair follicle, including the hair and inner root sheath, were also labelled. Non-keratinized tissues including junctional epithelium, embryonic epidermis and diestrus vaginal epithelium showed little or no Fos labelling. With the onset of keratinization at 18 days gestation or with induction of estrus in ovariectomized mice with estradiol benzoate, the epidermis and vagina expressed Fos protein in the manner typical for keratinized tissues. The Er/Er mutant epidermis, a tissue that is blocked in its ability to keratinize, overexpresses Fos with Fos-positive cells appearing in virtually every cell layer. Gel shift analysis demonstrates the presence of a functional AP 1 complex in epidermal extracts that is recognized by our antibody. Our data suggest that the expression of Fos is intricately related to epithelial cell differentiation, specifically in relation to the process of cornification and cell death. PMID- 1909951 TI - [The provocation of dynamic obstruction of the left ventricular outflow tract in secondary myocardial hypertrophy]. AB - The effect of the Valsalva manoeuvre before and after sublingual administration of 1.6 mg nitroglycerin on maximal velocity (Vmax), acceleration time (AT) and ejection time (ET) of left-ventricular outflow was measured by Doppler echocardiography in 49 patients (28 men and 21 women; mean age 65 [48-84] years) with secondary left-heart hypertrophy, and in 8 controls. Changes in flow profile typical of dynamic obstruction in the left-ventricular outflow tract (LVOT) occurred in 30 of the patients, Vmax increasing from a mean of 137 to 302 cm/s. Latent LVOT obstruction was associated with a thickened posterior wall, an accelerated left-ventricular outflow even at rest and systolic anterior motion of the anterior mitral leaflet (SAM phenomenon). The size of the provoked LVOT gradient correlated significantly with Vmax or the AT/ET ratio at rest. Obstruction of the LVOT is apparently a non-specific phenomenon which also occurs in secondary left-heart hypertrophy. These findings may have therapeutic consequences. PMID- 1909953 TI - Microsurgically generated discontinuities provoke heritable changes in cellular handedness of a ciliate, Stylonychia mytilus. AB - Stylonychia mytilus is a dorsoventrally flattened ciliate with compound ciliary structures arranged in a specific manner on the cell surface. In mirror-image (MI) doublets of this ciliate, two nearly complete sets of ciliary structures are arrayed side-by-side, one in a normal or 'right-handed' (RH) arrangement, the other in a reversed or 'left-handed' (LH) arrangement. MI-doublets exist in two forms, one with the RH component on the right, the LH component on the left, and feeding structures near the center ('buccal-adjoining MI-doublet'); the other with the RH component on the left, the LH component on the right, and feeding structures on the lateral edges ('buccal-opposing MI-doublet'). We describe an operation that can generate either type of MI-doublet. This operation interchanges large anterior and posterior regions of the cell, transposing the original posterior region anteriorly (P----A) and the original anterior region posteriorly (A----P), while retaining the original anteroposterior polarity of each region. Two sets of new ciliary structures then are formed in mirror-image arrangement, with the set in the P----A region oriented normally and the set in the A----P region undergoing a reversal of polarity along its anteroposterior axis. This sometimes creates end-to-end MI forms, but more commonly produces side by-side MI-doublets through a folding together of the P----A and A----P regions. This folding occurs because one lateral edge of the cell had been removed during the operation; if the left edge was removed, the complex folds to the left and forms a buccal-adjoining MI-doublet, whereas if the right edge was removed, the complex folds to the right and forms a buccal-opposing MI-doublet. Both types can reorganize and later divide true-to-type, although the 'buccal-opposing' type is by far the more stable of the two. The generation of mirror-image forms is dependent on the prior abnormal juxtaposition of regions from opposite ends of the cell, and involves a coordinated respecification of large-scale organization. We interpret this response to be a consequence of intercalation of missing intervening positional values in the zone of posterior-anterior abutment. PMID- 1909955 TI - Use of recovery VO2 to predict running economy. AB - The purpose of this study was to determine whether running economy (RE) could be predicted accurately using recovery VO2 values. Twelve runners (means VO2max = 61.9, SD 4.9 ml.kg-1.min-1) completed three treadmill RE sessions over a 2-week period. During each session, subjects performed three 6-min runs at 69%, 78%, and 87% VO2max. RE was calculated from a single 2-min gas collection during the last 2 min of running. Immediately following each run, recovery VO2 data obtained during randomly assigned 15-s, 20-s, or 25-s gas collections were used to predict exercise VO2. Correlations and mean absolute percentage variation (% VAR) between actual and predicted VO2 at each relative intensity and recovery period are reported. Although the relationship between actual and predicted VO2 was significant and more pronounced at higher exercise intensities, the overall magnitude of the association was low to moderate (r range = 0.50-0.81). The range of % VAR between actual and predicted aerobic demands also obscured marked underprediction (-6.5% to -12.5%) and overprediction (+10.1% to +17.4%) of actual VO2 in some subjects. These data suggest that 15-, 20-, and 25-s recovery VO2 values do not correlate strongly with steady-state VO2, nor do they adequately account for variation in individual economy profiles. PMID- 1909954 TI - Independent roles of centrosomes and DNA in organizing the Drosophila cytoskeleton. AB - The early embryonic divisions of Drosophila melanogaster are characterized by rapid, synchronized changes of the nuclei and surrounding cytoskeleton. We report evidence that these changes are carried out by two separately organized systems. DNA was sufficient to cause assembly of nuclear lamina and the formation of nuclear membrane with pore structures. Free centrosomes were correlated with the formation of microtubule, microfilament and spectrin networks in the absence of nuclei. In addition, we found that the morphology of the cytoskeleton associated with the free centrosomes cycled in response to the embryonic cell cycle cues. These observations suggest that the centrosomes may be responsible for the organization of this extensive cytoskeleton. The early divisions may therefore result from the independent cycling of two systems, the nucleus and the surrounding cytoskeleton, that respond separately to the mitotic cues in the embryo and function together to give the synchronized early divisions. The Drosophila embryo has an "intermediate" mitotic system in which the nuclear membrane does not break down completely during mitosis. We speculate that the principles of cytoskeleton organization in this system may be different from those of the Xenopus "open" mitotic system. PMID- 1909956 TI - Role of central serotonergic neurons in the effect of sertraline in rats in the forced swimming test. AB - Sertraline, administered i.p. in single doses or as three injections in 24 h, significantly reduced the immobility of rats in the forced swimming test at 64 and 100 mumol/kg. The effect of three doses of 64 mumol/kg in 24 h was not modified in animals treated i.p. with metergoline (5 mg/kg) 3 h before testing. I.c.v. administration of 150 micrograms 5,7-dihydroxytryptamine, which depleted brain serotonin, or infusion of 6 micrograms 6-hydroxydopamine in the locus coeruleus, which markedly depleted noradrenaline in terminal regions, was also ineffective. The effect of 64 mumol/kg sertraline, once daily for 7 days, was not modified by i.c.v. 5,7-dihydroxytryptamine. The effect of three doses of 64 mumol/kg sertraline in 24 h was instead completely antagonized by 100 mg/kg sulpiride given 90 min before testing. The exact mechanism of this effect and its relevance for the favourable effects of sertraline in human depression remain to be clarified. PMID- 1909958 TI - Evidence against a role of arachidonic acid metabolites in autoregulatory responses of the isolated perfused kidney of the rat. AB - The role of arachidonic acid metabolites in renal autoregulatory responses to changes in pressure was examined in rat isolated perfused kidneys. We also studied the influence of diabetes, a condition associated with hyperfiltration and altered renal eicosanoid production, on autoregulatory responses. The perfused rat kidney demonstrated autoregulation of flow within a pressure range of 100-150 mm Hg, with no differences between diabetic and control rat kidneys. Nifedipine resulted in vasodilatation and loss of autoregulation. Inhibition of the cyclooxygenase pathway of arachidonic acid metabolism with indomethacin failed to alter autoregulatory capacity. Similarly, inhibition of lipoxygenase with BW755C or NDGA, or inhibition of cytochrome P450-dependent enzymes with NDGA, clotrimazole or 7-ethoxyresorufin were without effect on autoregulatory responses. In vivo treatment with stannous chloride to deplete renal cytochrome P450-dependent enzymes also failed to modify autoregulatory responses. These results argue against a role of arachidonic acid metabolites in autoregulation of perfusate flow in the isolated kidney. PMID- 1909957 TI - Influence of SK&F 96148 on thromboxane-mediated responses in the airways of the cat. AB - The effects of SK&F 96148, a thromboxane receptor blocking agent, on bronchoconstrictor responses were investigated in paralyzed, anesthetized, mechanically ventilated cats. I.v. injections of the thromboxane A2 (TXA2) mimics, U-46619 and U-44069, produced dose-related increases in transpulmonary pressure and lung resistance (RL) and decreases in dynamic compliance (Cdyn). After administration of SK&F 96148, 5 mg/kg i.v., bronchoconstrictor responses to U-46619 and U-44069 were reduced markedly, whereas airway responses to prostaglandin (PG) F2 alpha, serotonin, PGD2, or the PGD2 metabolite, 9 alpha, 11 beta-PGF2, were not altered. The duration of action of SK&F 96148 was greater than 2 h, and the TXA2 receptor blockade was overcome when 10-fold larger doses of the TXA2 mimics were administered. Bronchoconstrictor responses to arachidonic acid, platelet-activating factor (PAF), endothelin-1, and E. coli endotoxin were blocked by SK&F 96148. The present data suggest that SK&F 96148 has selective thromboxane receptor blocking activity in the airways of the cat, and that bronchoconstrictor responses to endothelin-1, arachidonic acid, PAF, and E. coli endotoxin are mediated in part by the formation of TXA2. PMID- 1909959 TI - Role of 5-HT receptors in the effect of d-fenfluramine on gastric emptying and feeding behaviour as examined in the runway test. AB - In one experiment, the effect of d-fenfluramine (DF) on gastric emptying was studied in rats treated i.p. with metergoline, a non-selective serotonin (5-HT) receptor antagonist, ritanserin, a selective 5-HT2 and 5-HT1C receptor antagonist, and xylamidine, a 5-HT antagonist which has poor access to the brain. Metergoline (1 mg/kg) but not ritanserin (0.5 mg/kg) or xylamidine (3 mg/kg) blocked the effect of 2.5 mg/kg DF studied 2 and 4 h after injection. In a second experiment, we studied the ability of metergoline to antagonise the effect of DF, administered after a meal, on runway performance, food intake and gastric emptying assessed 4 h later. Metergoline at a dose of 1 mg/kg did not antagonise the effect of DF (2.5 mg/kg) on runway performance but completely blocked the effect on gastric emptying. The data clearly show that DF delays gastric emptying by indirectly activating 5-HT1 receptors; this effect is not important for the ability of DF to reduce runway performance and food intake when the drug is injected after a pre-feeding period. While there is evidence that DF hastens the termination of the meal by a 5-HT mechanism, the data suggest that DF may prolong the satiating effect of food during the post-absorptive phase by mechanisms other than 5-HT. PMID- 1909960 TI - Baclofen and noradrenergic function in the rat frontal cerebral cortex. AB - Possible changes in noradrenergic function were investigated in rat frontal cerebral cortex after acute treatment (1, 2 h) with the GABAB agonist, baclofen. A single i.p. injection of d,l-baclofen 10 mg/kg both reduced noradrenaline (NA) biosynthesis in vivo (31%) and the endogenous concentration of normetanephrine (NMN) (32%) and increased NA levels (28%). Increased [3H]NA uptake (15%) and [3H]dihydroxyphenyl-ethyleneglycol ([3H]DOPEG formation (39%) were observed in cortex slices ex vivo from baclofen-treated animals. The activity of monoamineoxidase (MAO) was unchanged after baclofen treatment. We suggest that baclofen might interfere in vivo with noradrenergic neurotransmission, reducing NA biosynthesis and release in the rat cerebral cortex. PMID- 1909961 TI - Dipyridamole potentiates the anti-aggregating and vasodilator activity of nitric oxide. AB - The interaction between dipyridamole and nitric oxide (NO) was studied using isolated rabbit platelets and segments of the rabbit aorta. Dipyridamole potentiated the anti-aggregating activity of authentic NO when platelet aggregation was induced by the thromboxane A2 mimetic U-46619 or adenosine diphosphate (ADP). This potentiation was also seen when washed rabbit platelets were exposed to aortic effluent containing endothelium-derived NO. In the thoracic aorta dipyridamole hardly influenced the endothelium-dependent relaxations induced by acetylcholine. However, dipyridamole clearly enhanced the dilatation caused by exogenous NO from four different sources, including endothelial cells. PMID- 1909962 TI - Comparative effects of arginine vasopressin, [pGlu4,Cyt6]arginine vasopressin-(4 9) and nerve growth factor on maintenance of functional tolerance to ethanol in mice. AB - Previous work has demonstrated that arginine vasopressin (AVP), acting in the CNS, can maintain functional tolerance to ethanol. We now show that the AVP metabolite peptide, [pGlu4,Cyt6]arginine vasopressin-(4-9), also maintains ethanol tolerance, with a potency similar to that of arginine vasopressin, while nerve growth factor has only a marginal effect. The effects of these peptides on ethanol tolerance correlate with their previously described ability to induce expression of the proto-oncogene, c-fos, in the septum, a putative mechanism underlying peptide effects on neuroadaptive processes. PMID- 1909963 TI - Effects of TZI-41127, a novel selective 5-lipoxygenase inhibitor, on A23187 induced pleurisy in rats. AB - Intrapleural injection of the ionophore A23187 in rats induced leukotriene (LT) production, prostaglandin E2 production, plasma exudation and leukocyte accumulation in the pleural cavity. We evaluated the inhibitory effects of orally administered drugs on 5-lipoxygenase activity by their ability to reduce the content of both peptido-LTs (LTC4, LTD4 and LTE4) and LTB4 in this model. TZI 41127, a novel selective 5-lipoxygenase inhibitor, significantly reduced the peptido-LTs and LTB4 content with ED50 values of 4.2 and 6.1 mg/kg, respectively, whereas it only reduced the prostaglandin E2 content (cyclooxygenase activity) by 31.1% even after 100 mg/kg. Phenidone inhibited 5-lipoxygenase activity more selectively than cyclooxygenase activity. BW755C inhibited cyclooxygenase activity more selectively than 5-lipoxygenase activity. Indomethacin selectively inhibited cyclooxygenase activity. These results suggest that: (1) A23187-induced pleurisy is an convenient in vivo model for studying drug effects on 5 lipoxygenase and cyclooxygenase activities and (2) TZI-41127 is an orally active and comparatively selective inhibitor of 5-lipoxygenase activity. PMID- 1909964 TI - Phosphorylation of Gi protein by cyclic AMP-dependent protein kinase inhibits its dissociation into alpha-subunits and beta gamma-subunits by Mg2+ and GTP gamma S. AB - Pretreatment of partially purified inhibitory GTP-binding protein (Gi, 41 kDa) with activated cyclic AMP-dependent protein kinase (PKA) decreases its ADP ribosylation by islet-activating protein (pertussis toxin, IAP). We examined whether this decrease was associated with dissociation of the trimer of alpha beta gamma-subunits of Gi protein into alpha-subunits and beta gamma-subunits. Results showed that phosphorylation of the Gi protein by PKA impaired its dissociation into alpha-subunits and beta gamma-subunits by 50 mM Mg2+ and 100 microM GTP gamma S. The results suggested that phosphorylation of the Gi protein by PKA possibly caused a conformational change of the trimer Gi protein. PMID- 1909965 TI - Diacylglycerol lipase and the contractile action of epidermal growth factor urogastrone: evidence for distinct signal pathways in a single strip of gastric smooth muscle. AB - In guinea pig gastric longitudinal muscle preparations, wherein epidermal growth factor-urogastrone (EGF-URO) causes contraction via the generation of arachidonate-derived prostaglandins, the specific diacylglycerol lipase (DG lipase) inhibitor, U57,908 (formerly designated RHC 80267) completely blocked EGF URO and transforming growth factor-alpha (TGF-alpha)-mediated contraction, without affecting contractions caused by other agonists such as bradykinin, prostaglandin F2 alpha or arachidonic acid (AA). In contrast, the contractile actions of EGF-URO and TGF-alpha on the gastric circular muscle component, present in the same tissue strip as the longitudinal muscle preparation, were unaffected by concentrations of U57,908 that maximally inhibited contraction in the longitudinal muscle preparation. We conclude that in the longitudinal muscle preparation, EGF-URO acts not by the activation of phospholipase A2, but rather via the metabolism of diacylglycerol by DG lipase, thereby liberating arachidonic acid for the synthesis of contractile prostanoids. We also conclude that, even in the same tissue, the effects of EGF-URO on anatomically different components (longitudinal muscle versus circular muscle) can be mediated via two quite distinct signal transduction pathways. PMID- 1909966 TI - Inhibition of heat shock protein synthesis and protein glycosylation by stepdown heating. AB - Mammalian cells exhibit increased sensitivity to hyperthermic temperatures of 38 43 degrees C after an acute high-temperature heat shock; this phenomenon is known as the stepdown heating (SDH) effect. We characterized the SDH effect on (1) the synthesis of major heat shock proteins, HSP110, 90, 72/70, 60 (35S-amino acids label), (2) on heat-induced protein glycosylation (3H-D-mannose label), and (3) on thermotolerance expression, using cell survival as an endpoint. Partitioning of label between soluble and insoluble cell fractions was separately examined. Synthesis of high molecular weight HSPs (HSP110, 90, and 72/70) was increased both by acute (10 min, 45 degrees C) and chronic (1-6 h, 41.5 degrees C) hyperthermia, primarily in the soluble cytosol fraction. SDH (10 min, 45 degrees C + 1 to 6 h, 41.5 degrees C) completely inhibited labeling of HSP110, partially inhibited HSP90 labeling, and had virtually no effect on HSP72/70 synthesis, when compared with chronic hyperthermia alone. At the cell survival level, SDH increased sevenfold the rate of cell killing at 41.5 degrees C, but reduced the expression of thermotolerance by only a factor of two. This suggests that SDH sensitization did not result from changes in HSP72/70 synthesis, nor solely from inhibition of thermotolerance. 35S-labeled HSP60 and HSP50 were found primarily in the cellular pellet fraction after both acute and chronic hyperthermia. SDH completely inhibited 35S-labeling of both HSP60 and HSP50. Labeling of GP50 with 3H-D-mannose was also completely inhibited by SDH. Moreover, SDH progressively reduced N-acetylgalactosaminyl-transferase activity. The data demonstrate that heat sensitization by SDH is accompanied by complex and selectively inhibitory patterns of HSP synthesis and protein glycosylation. Profound inhibition of HSP110, HSP60, and HSP50/GP50 labeling suggests that these may be associated with mechanisms of SDH sensitization. PMID- 1909967 TI - Dimethyl sulfoxide inhibits the expression of early growth-response genes and arrests fibroblasts at quiescence. AB - We have previously shown that dimethyl sulfoxide (DMSO) treatment of mouse embryo fibroblasts (MEF) at the early hours of mitogenic stimuli resulted in the inhibition of DNA and protein synthesis; delayed treatment of serum-stimulated cells with DMSO had little effect on the synthesis of these macromolecules. Here, we demonstrate the specific inhibition of expression of early growth response genes by DMSO in serum-stimulated MEF. The expression of interleukin 6, and of oncogenes c-myc and c-fos were inhibited when the cells were treated with 2% DMSO from the beginning of serum-stimulated growth but not after 3 h of mitogenic stimuli. Although the actin gene is an early serum-response gene, its expression was not affected by DMSO. The synthesis of another serum-induced protein, the plasminogen activator inhibitor-1 was blocked during concurrent and delayed (after 3 h of stimulation) treatment of serum-stimulated fibroblasts with DMSO. The expression of glyceraldehyde-3-phosphate dehydrogenase gene was not affected by DMSO. These results indicate that the expression of non-growth-related genes are either not affected or affected nonspecifically both at early and late stages of serum-induced growth of mouse embryo fibroblasts. The serum-induced expression of c-fos gene was abolished by DMSO treatment of MEF while the phorbol 12 myristate 13-acetate-induced expression of fos gene was not, indicating that the PMA signaling pathway was refractory to DMSO. Treatment of cells with medium containing 2% DMSO for 24-48 h prevents them from progression into cell cycle by preventing the expression of genes involved in G0-G1 transition of quiescent cells. PMID- 1909968 TI - Mechanism of suppression of normal hemopoietic activity by lymphokine-activated killer cells and their products. AB - Interleukin 2 (IL-2)-activated lymphocytes (lymphokine-activated killer [LAK] cells) have been shown to inhibit the formation of autologous human granulocyte macrophage hemopoietic progenitors (granulocyte-macrophage colony-forming units, CFU-GM) in vitro. Effects of LAK cells on these progenitors may include a number of different mechanisms. LAK cells are potent cytotoxic lymphocytes capable of lysing certain normal autologous cells. They also produce cytokines known to inhibit hemopoiesis (interferon gamma [IFN-gamma] and tumor necrosis factor alpha [TNF-alpha]) or enhance it (granulocyte-macrophage colony-stimulating factor, GM CSF). In our current study we analyzed the mechanism of suppression of autologous CFU-GM by LAK cells. Our results suggest that LAK cells are not directly cytotoxic to normal CFU-GM. We show that it is possible to abolish the hemopoiesis-inhibiting activity of LAK cells without abrogating their cytotoxicity against tumor cell lines using inhibitors of DNA synthesis, namely hydroxyurea or irradiation. PMID- 1909970 TI - Purification and amino acid analysis of a human macrophage cytotoxicity-inducing factor (MCF). AB - Recently we have described a CD4+ human T-cell hybridoma Ft.F3 (ATCC HB 9713). This hybridoma produces two proteins having molecular weights of 29 kd (P29) and 14.7 kd (P14.7) that function as activators of human monocyte tumor cytotoxicity and interleukin 1 (IL-1) synthesis (macrophage cytotoxicity-inducing factors, MCFs). Both MCF species were purified to apparent homogeneity, as assessed by two dimensional (2D) gel electrophoresis, by a combination of dye ligand, ion exchange, and hydrophobic interaction chromatography, and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Exhaustive treatment of P29 by endoglycosidase F, performic acid, and 40x molar excess 2-mercaptoethanol failed to generate P14.7 from P29. Antisera raised to P29 recognized only P29 in immunoblots of 2D gels of crude hybridoma supernatant. Amino acid composition analyses of both species are similar but not identical. These MCFs appear to be distinct but possibly related proteins important in the inflammatory response, whereas N-terminal analysis of P29 reveals it to be a previously undescribed cytokine. PMID- 1909969 TI - Recombinant human interleukin 6 is a potent inducer of the acute phase response and elevates the blood platelets in nonhuman primates. AB - Human interleukin 6 (IL-6) produced by molecular cloning was administered to nonhuman primates to assess its biological activities in vivo. Rhesus monkeys were treated s.c. with recombinant human (rh) IL-6 at 3 and 30 micrograms/kg body weight/day for 11 days, followed by the administration of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) at 5.5 micrograms/kg/day for 5 days. Serum levels of positively regulated acute phase proteins (APP) (C-reactive protein, alpha 1-antitrypsin, haptoglobin, and ceruloplasmin) increased, whereas negatively regulated APP (prealbumin) decreased in response to rhIL-6 treatment in a dose-dependent manner. Platelet counts rose after a latent period of 4-5 days following the start of rhIL-6 treatment, resulting in a maximum twofold increase above normal levels 2-3 days after the termination of the rhIL-6 treatment. Recombinant human IL-6 treatment induced a two to threefold rise in myeloid progenitor blood cell levels. The subsequent administration of rhGM-CSF to rhIL-6-pretreated animals did not increase the progenitor cell levels in blood above those found with rhGM-CSF treatment alone, indicating that rhIL-6 compared to recombinant human interleukin 3 (rhIL-3) has a minor proliferative effect on hematopoietic precursors in vivo. In conclusion, rhIL-6 was shown to be a potent stimulator of APP and was able to increase the number of platelets in circulation in nonhuman primates. PMID- 1909971 TI - Folding around the C-terminus of human carbonic anhydrase II. Kinetic characterization by use of a chemically reactive SH-group introduced by protein engineering. AB - We are characterizing the process of refolding of the enzyme human carbonic anhydrase II from the denatured state in guanidine hydrochloride. To describe the folding in defined parts of the protein we use protein engineering to introduce cysteine residues as unique chemically reactive probes. The accessibility of the cysteine SH-group to the alkylating reagent iodoacetate, at different stages during refolding, is used to give a kinetic description of the folding process. The structuration of the C-terminal part of the polypeptide chain, which is involved in a unique 'knot' topology, was investigated. Our results show that the structure around the C-terminal, composed of the outermost beta-strands in a dominating beta-structure that extends through the entire protein, is formed relatively late during refolding. In contrast, it was found that beta-strands located in the interior of the protein were structured very rapidly. The final native structure is formed in a process that is slower than those observed for formation of beta-structure. PMID- 1909972 TI - A novel brain-specific 25 kDa protein (p25) is phosphorylated by a Ser/Thr-Pro kinase (TPK II) from tau protein kinase fractions. AB - A novel brain-specific 25 kDa protein (p25) was purified from a bovine brain extract. The protein was phosphorylated by Ser/Thr-Pro kinase (TPK II) in tau protein kinase fractions at the Ser residues of Ser-Pro sequences. Using immunoblot analysis, the protein was found only in brain extracts, and was most abundant in the brain regions such as cerebrum and hippocampus, but less abundant in cerebellum, medulla oblongata and olfactory bulb. The protein was detected in rat, bovine and human brain extracts, indicating that this protein specifically exists in mammalian brain tissues. PMID- 1909973 TI - Immunological characterization of peptidyl-glycine-alpha-amidating monooxygenases. AB - Antibodies to the soluble form of the copper-containing enzyme, peptidyl-glycine alpha-amidating monooxygenase isolated from secretory granules of bovine pituitary anterior lobes were found to belong to immunoglobulin G1. The antibodies were used to study the subcellular distribution of the enzyme in this tissue, and positive tests were found only for granular and cytosol fractions. The antibodies do not crossreact with other copper-containing systems of secretory granules, such as neurocuprein and dopamine-beta-monooxygenase. It was shown that the antibodies give the crossreaction with the enzyme isolated from secretory granules of bovine pituitary anterior lobes, cardiac atria, pancreas and adrenal medulla, indicating the antigenic identity of the enzyme from secretory granules of different glands. PMID- 1909974 TI - Protein kinase C subtypes in endothelial cells. AB - Activation of protein kinase C (PKC) has been linked to the regulation of class II expression on endothelial cells by interferon-gamma (IFN-gamma). PKC subtypes in endothelial cells were analyzed using three different approaches, the immunoperoxidase staining of native and IFN-gamma stimulated cells cultured on chamber slides as well as immuno- and Northern blotting. All approaches revealed that of the conventional subtypes, alpha is the predominant form of PKC in endothelial cells. Even though IFN-gamma is able to induce PKC translocation to particulate fractions, no translocation was detected in histological stainings. Western blot studies as well as mRNA studies revealed that IFN-gamma is unable to increase the total amount of PKC in endothelial cells. PMID- 1909975 TI - Pituitary hormone response to thyrotropin-releasing hormone in secondary amenorrheic women associated with simple weight loss. AB - OBJECTIVE: To investigate endocrine dysfunction in simple weight loss amenorrhea. DESIGN: We studied pituitary hormone responses to thyrotropin-releasing hormone (TRH) in 10 women with simple weight loss amenorrhea. SETTING: Department of Obstetrics and Gynecology, University Hospital, University of Tokushima at Tokushima, Japan. PATIENTS, PARTICIPANTS: Secondary amenorrheic women associated with simple weight loss who did not have anorexia nervosa. INTERVENTIONS: Intravenous injection of 500 micrograms of synthetic TRH. MAIN OUTCOME MEASURE: Serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), thyrotropin, and prolactin were measured before and 15, 30, and 60 minutes after TRH injection. RESULTS: In normally menstruating women on day 7 of the cycle TRH did not affect serum LH and FSH levels. In women with simple weight loss amenorrhea, however, TRH raised serum LH and FSH levels significantly (P less than 0.01, respectively). Prolactin response to TRH was significantly (P less than 0.05) lower in women with simple weight loss amenorrhea than in normally menstruating women. CONCLUSIONS: These results indicate that TRH causes a significant rise in serum LH and FSH and the impaired prolactin response in women with simple weight loss amenorrhea. PMID- 1909976 TI - Exogenous versus endogenous pulses of luteinizing hormone-releasing hormone and secretory patterns of gonadotropins. AB - OBJECTIVE: Does an exogenously administered regimen of luteinizing hormone releasing hormone (LH-RH) pulses override endogenous LH-RH? DESIGN: Pulses of LH RH were given intravenously during 1 week with intervals of 90 (n = 5) or 120 minutes (n = 5). Before, during, and after treatment serial plasma luteinizing hormone (LH) and follicle-stimulating hormone (FSH) patterns and pituitary responsiveness to LH-RH were estimated. PATIENTS: Women with virtual absence of gonadal function (postmenopause, gonadal dysgenesis, and premature menopause). RESULTS: During treatment with the 90-minute interval, no LH pulses that were not related to injections of LH-RH were observed. Two spontaneous LH pulses were observed during treatment with the 120-minute interval. Immediately after treatment, a lowered incidence of spontaneous LH pulses was seen of 3 pulses/6 h if LH-RH had been given every 90 minutes and to 1.5 pulses/6 h after the 120 minute interval treatment. Gonadotropin responses to 100 micrograms of LH-RH were attenuated during treatment but recovered within 48 hours after discontinuation of treatment. CONCLUSIONS: (1) Exogenously administered LH-RH can override endogenous LH-RH or its effects on the release of LH in women with hypergonadotropic hypogonadism; (2) during pulsatile LH-RH treatment desensitization of the pituitary occurs to some degree; and (3) immediately after cessation of treatment with pulsatile LH-RH, spontaneous LH pulses are present but with a significantly lower incidence. PMID- 1909977 TI - Early pituitary desensitization and ovarian suppression with leuprolide acetate is associated with in vitro fertilization-embryo transfer success. AB - OBJECTIVE: To determine if the timing of the onset of pituitary desensitization and ovarian suppression using follicular phase leuprolide acetate (LA) is associated with in vitro fertilization-embryo transfer (IVF-ET) success for pregnancy. DESIGN: Retrospective series of IVF patients undergoing pituitary desensitization and ovarian suppression before beginning controlled ovarian hyperstimulation for IVF-ET. SETTING: Tertiary infertility practice. PATIENTS: Seventy-eight women for 80 cycles began LA on day 1 of their menstrual cycle. After 11 days of LA, 47 (59%) cycles in group I had suppressed serum estradiol (E2) levels less than 40 pg/mL, in contrast to 33 (41%) cycles in group II not adequately suppressed, thereby requiring additional days to achieve suppression. INTERVENTIONS: Controlled ovarian hyperstimulation was started when patients were satisfactorily suppressed, i.e., E2 less than 40 pg/mL. MAIN OUTCOME MEASURE(S): Mean E2 response, ampules of human menopausal gonadotropin, cancellation rates, number of oocytes retrieved, fertilization rates, and pregnancy rates (PRs) per cycle were examined between groups I and II. RESULTS: Group I demonstrated a greater mean E2 response on the day of human chorionic gonadotropin 1,735 pg/mL versus 1,470 pg/mL (P = 0.008), a greater fertilization rate 64% versus 55% (P = 0.02), and a higher PR per cycle 34% versus 12% (P = 0.036) compared with group II. CONCLUSIONS: Women who achieved desensitization-suppression within 11 days of initiating LA demonstrated a more favorable outcome for IVF-ET than those who did not. PMID- 1909978 TI - A controlled study of gonadotropin-releasing hormone agonist (buserelin acetate) for folliculogenesis in routine in vitro fertilization patients. AB - STUDY OBJECTIVE: To determine if gonadotropin-releasing hormone agonist (GnRH-a) and gonadotropin therapy could improve folliculogenesis and pregnancy rates (PRs) in women with a previously satisfactory response to clomiphene citrate and human menopausal gonadotropin (hMG). DESIGN: Randomized prospective study. SETTING: Assisted reproduction clinic. PATIENTS: One hundred fifty-seven women were randomized to receive either hMG alone or the GnRH-a buserelin acetate 600 microgram/d or buserelin acetate 1,200 microgram/d plus hMG. RESULTS: Compared with hMG alone, pretreatment with buserelin acetate significantly increased the PR per cycle started by preventing a premature luteinizing hormone rise and thereby reducing the number of abandoned cycles. There was, however, no difference between the number of follicles aspirated, oocytes obtained, or fertilization rates between groups. Furthermore, agonist therapy significantly increased both the dose of hMG required and the duration of stimulation. CONCLUSION: The routine use of GnRH-a in in vitro fertilization programs must be questioned. PMID- 1909979 TI - Intramural-isthmic fallopian tube anastomosis facilitated by the carbon dioxide laser. AB - Proximal tubal obstruction is encountered in 33% of women with tubal factor infertility. Traditional microsurgery and the most recent transcervical tuboplasty have achieved 20% to 30% intrauterine PR. Microdissection of the intramural segment of the fallopian tube with the CO2 laser, resection of the scarred tissue, and microsurgical tubal reanastomosis has resulted in 100% tubal patency and 71% intrauterine PRs. PMID- 1909980 TI - An analysis of strokes in a rural hospital. AB - A four-year retrospective analysis of strokes in a rural hospital was undertaken for comparison with other areas as well as to understand the impact of the DRG system on the rural hospital. Risk factors, studies, treatment, disposition as well as resource considerations were all evaluated. PMID- 1909981 TI - [The characteristics of endocrine system functioning in the native inhabitants of the northeastern USSR. I. The thyroid status]. PMID- 1909982 TI - [The indices of oxygen and CO2 tension in the blood of divers at the breakpoint of maximal voluntary apnea performed after hyperventilation]. PMID- 1909983 TI - Detection of preclinical Parkinson's disease with PET. AB - Putamen 18F-dopa uptake of patients with Parkinson's disease (PD) is reduced by at least 35% at onset of symptoms; therefore, positron-emission tomography (PET) can be used to detect preclinical disease in clinically unaffected twins and relatives of patients with PD. Three out of 6 monozygotic and 2 out of 3 dizygotic unaffected PD co-twins have shown reduced putamen 18F-dopa uptake to date. In addition, an intact sibling and a daughter of 1 of 4 siblings with PD both had low putamen 18F-dopa uptake. These preliminary findings suggest there may be a familial component to the etiology of PD. PET can also be used to detect underlying nigral pathology in patients with isolated tremor and patients who become rigid taking dopamine-receptor blocking agents (DRBAs). Patients with familial essential tremor have normal, and those with isolated rest tremor have consistently low, putamen 18F-dopa uptake. Drug-induced parkinsonism is infrequently associated with underlying nigral pathology. PMID- 1909984 TI - Long-term care patients in acute care beds: a community-based analysis. AB - This paper describes an analysis of hospital utilization by alternate care patients, those who receive long-term care in hospital beds because postdischarge services are not available. During a 3-year period, the number of hospital beds occupied by these patients in Syracuse, New York reached 184, or 14% of the area's medical-surgical capacity. These patients were heterogeneous with respect to disposition, age, functional ability, and payor status. For this reason, the control of hospital alternate care should involve the management of admissions to nursing homes, home care, and elderly housing in a focused manner. PMID- 1909985 TI - Relationships between home care clients and their workers: implications for quality of care. AB - In-depth interviews were conducted with 54 home care clients and their home health aides and personal care attendants. The interview data reveal that home care relationships tend to be both formal and informal, in that job responsibilities tend to be diffusely defined and home care workers often become involved in the "backstage" world of their clients. The study also suggests, however, that personal bonds may be problematic for both workers and clients. For workers there is the risk of exploitation; for clients, there is the potential for loss of control over their own care. The quality of relationships also affects quality of care. PMID- 1909986 TI - Special care units: a typology of care settings for memory-impaired older adults. AB - After rating 55 nursing homes in five states, we created a typology of care settings that included eight distinct types of units designed to care for memory impaired older adults. SCUs appeared to be associated with higher quality care than were traditional units, although quality of SCU care was not uniformly outstanding. This typology provides guidelines that can be used in preresidential analysis of prospective care units for demented older adults. PMID- 1909987 TI - Falling into the Medicaid gap: the hidden long-term care dilemma. AB - This study describes the income, health, and functional capacity of older Florida residents who fall into the Medicaid gap--those whose incomes are too high to obtain eligibility for Medicaid yet too low to cover the cost of nursing home care as private pay patients--and examines the strategies adopted by their primary caregivers. Our findings suggest that few strategies succeed in alleviating this all but unresolvable problem, that those caught in the gap receive inadequate medical care, and that their primary caregivers face tremendous financial and emotional burdens with little hope for relief. PMID- 1909988 TI - Hydroxynonenal, a component of clastogenic factors? AB - Exposure of human lymphocyte cultures to superoxide generated by the xanthine xanthine oxidase (X-XO) system, resulted in formation of a clastogenic factor (CF), as expected from previous work. We speculated that arachidonic acid (AA), the major polyunsaturated fatty acid of biological membranes, was oxidized via the cyclooxygenase-lipoxygenase pathways or nonenzymatically by oxygen free radicals in the culture medium to products with clastogenic properties. In the present study, we analyzed CF for AA-derived products and tested corresponding commercial standards for their clastogenic properties. The results show that prostaglandins, thromboxane, and H(P)ETEs were not increased in supernatants from X-XO treated cultures compared to untreated cultures. Synthetic H(P)ETEs added to the medium of lymphocyte cultures were only slightly or not clastogenic. In contrast hereto, the degradation product 4-hydroxynonenal was found in 50% of CF samples, while it was absent in all 43 control samples. The kinetics of detectability in the culture medium was similar to that of CF. Also, the clastogenic effect of synthetic 4-hydroxynonenal at concentrations as low as 0.1 microM suggested that this aldehyde, known for its genotoxic effects, was a clastogenic component of CF. The indirect action mechanisms of 4-hydroxynonenal via inactivation of functional SH groups in DNA polymerases, may explain why chromatid-type damage is predominant in lymphocytes exposed to CF in the Go-G1 phase of the cell cycle. This particularly was already stressed 20 years ago in the first observations of radiation-induced CF. However, 4-hydroxynonenal is not the only clastogenic component of CF.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1909989 TI - A preliminary report of combination chemotherapy with cisplatin and mitomycin-C followed by radical hysterectomy or radiation therapy in patients with locally advanced cervical cancer. AB - Neoadjuvant chemotherapy with cisplatin and mitomycin-C was used in the primary treatment of 17 patients with locally advanced cervical cancer (stages Ib-IIIb; tumor diameter greater than 5 cm) prior to definitive local treatment with radical hysterectomy or radiotherapy. Thirteen of the seventeen patients (76.5%) responded to initial chemotherapy, permitting a radical hysterectomy in ten patients. At histologic examination of the surgically resected primary tumor and lymph nodes, complete pathologic responses were found in 2 patients and partial pathologic responses in 8 patients. The median follow-up time is 14.5 months with a median survival for all patients of 52 weeks. All responders are alive. No therapy-related deaths, major complications, or delay in treatment occurred. Neoadjuvant chemotherapy with mitomycin-C and cisplatin is feasible and may be of benefit for patients with locally advanced cervical cancer. PMID- 1909990 TI - [The hyperstimulation syndrome]. PMID- 1909991 TI - Platelet aggregation in recombinant-hirudin-anticoagulated blood. AB - Recombinant hirudin (r-hirudin) inhibited the thrombin-induced aggregation and 14C-serotonin secretion of human platelets in the same concentration range as native hirudin. In r-hirudinized blood, lower spontaneous platelet aggregation was found than in citrated or heparinized blood. Except for a demonstrable aggregation-potentiating effect, adrenaline did not induce aggregation in r hirudin- or in citrate-anticoagulated blood. The lowest platelet adhesion to glass surface was found in r-hirudinized plasma. The ADP-induced aggregation was nearly the same in the three differently anticoagulated plasma samples: however, desaggregation predominated in r-hirudinized plasma. Adrenaline caused only a slight aggregation in r-hirudinized plasma. ADP and adrenaline caused 14C serotonin secretion in citrated plasma only. The collagen- as well as the PAF- and arachidonic-acid-induced aggregation did not differ significantly in the three plasma samples. Hence, r-hirudin is suitable for studying platelet functions at physiological calcium concentrations. PMID- 1909992 TI - Extending health care to AFDC recipients who obtain jobs: results of a demonstration. AB - This study investigated the outcomes of a demonstration project that provided free medical coverage to former Aid to Families with Dependent Children (AFDC) recipients who were holding jobs with limited or no health benefits. Data were collected on the Medicaid expenditures of 54 eligible participants and their dependents for up to two years before they exited welfare; the expenditures averaged 56 percent less for adults and 45 percent less for children than the respective AFDC averages for the county. Because only 22 percent of the eligible participants took advantage of the program, telephone interviews also were conducted with 24 people who did not participate in or dropped out of the health plan. The main reasons cited for not enrolling were a misunderstanding of the program, a claim that no notification of the program was received, and a lack of interest. These results and their policy implications are presented in the context of the Family Support Act's mandate that states extend medical assistance coverage to AFDC recipients whose cases are closed because of employment. PMID- 1909993 TI - "Cocooning": a clinical sign of depression in geriatric patients. PMID- 1909994 TI - Cim: an MHC class II-linked allelism affecting the antigenicity of a classical class I molecule for T lymphocytes. AB - Two alleles at the major histocompatibility complex (MHC)-linked locus cim determine "gain and loss" changes in the rat RT1.Aa class I molecule which affect its structure both as an alloantigen and as a restriction element. Alleles at the cim locus also influence the post-translational modification of RT1.Aa. These effects may reflect the participation of the cim gene product in the processes of peptide loading or assembly of RT1.Aa. In this study we have used the discriminating RT1.Aa-specific monoclonal antibody JY3/84, as well as cytotoxic T cells raised in appropriate combinations, to determine the cim alleles of eight haplotypes in 15 independent inbred strains of rat. We have also employed the same techniques to analyse a panel of F1 hybrid animals derived from various MHC recombinant strains. These experiments map the cim locus to the class II region of RT1, probably between the DP-related genes (RT1.H) and the DQ-related RT1.B alpha. PMID- 1909995 TI - Evolution of the rabbit immunoglobulin kappa chain genes. AB - We have analyzed the organization and the structure of rabbit kappa chain genes encoding b allotypes in wild rabbits. The kappa 1 gene of the b95 allotype was cloned and its structure determined. The J region is composed of five segments but only J2 appears to be functional and is identical to the J2 segment of the b4 allotype. The J region is highly conserved among the various b allotypes, whereas the constant region exon displays a high level of differences when compared with other allotypes (9%-30% of different amino acids). The b95 J region is closer to that of b4var and the constant region to b5 allotype constant region. Alignment of nucleotide sequences revealed that the constant region exon displays segmental similarities with b4 and bas constant regions. The mosaic structure of b95 allotype gene indicates that complex allotypes of kappa 1 genes may result from genetic exchanges or gene conversion between the different kappa genes. PMID- 1909996 TI - Achievement of surgically soft and safe eyes--a comparative study. AB - With the advent of intra ocular lens implantation at the time of cataract extraction, especially by intracapsular method, it has become very important to prevent the loss of vitreous during surgery. This can be achieved by lowering the intraocular pressure by various methods. In order to find out the best method to achieve a soft & safe eye before surgery, a study was conducted on 90 patients, undergoing intracapsular cataract extraction. The patients were divided into 9 groups of 10 each, & different methods of lowering intraocular pressure were tried and results compared. It was observed that intravenous mannitol given preoperatively and pressure with mercury column together, formed the best combination to achieve the maximum tension lowering effect. PMID- 1909997 TI - Neurofibromatosis irides with flat vertebra--a case report. PMID- 1909998 TI - Anthrax protective antigen interacts with a specific receptor on the surface of CHO-K1 cells. AB - The interaction of protective antigen (PA), a component of the anthrax toxin, with receptors on the Chinese hamster ovary cell line CHO-K1 was characterized. Protective antigen binding at 4 degrees C is highly specific, concentration dependent, saturable (Kd = 0.9 nM), and reversible. Scatchard analysis indicates the presence of a single class of PA binding sites at a concentration of 10,000 +/- 2,000 per cell. Pretreatment of cells with a number of different proteases strongly inhibits PA binding, suggesting that the receptor may be at least partially proteinaceous. Direct chemical cross-linking of radioiodinated PA to the cell surface results in the appearance of a major band exhibiting an apparent molecular mass of 170 kDa, as estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The appearance of this band is completely inhibited by a 200 fold molar excess of unlabeled PA, indicating a high specificity for this interaction. Our results suggest that a cell surface protein(s) of 85 to 90 kDa is, or constitutes a portion of, a specific receptor for the PA. PMID- 1909999 TI - Isolation, characterization, and molecular cloning of a specific Mycobacterium tuberculosis antigen gene: identification of a species-specific sequence. AB - A rabbit polyclonal antiserum exhibiting a specific recognition pattern for Mycobacterium tuberculosis proteins was used to screen an M. tuberculosis genomic library constructed in the expression vector lambda gt11. One clone, denominated C1:10, expressed M. tuberculosis-specific determinants as part of a large fusion protein with beta-galactosidase. The gene for this protein has been sequenced, and it encodes a protein of 134 amino acids (13.8 kDa) which did not display significant homology with any of the previously reported proteins in the data bases. Hybridization studies with restriction fragments of the cloned sequence revealed that it was not present in the genomes of related mycobacteria, namely, M. bovis, M. bovis BCG, M. flavescens, M. fortuitum, M. phlei, and M. vaccae. These findings suggest that we have detected a gene, or a fragment therefrom, unique for M. tuberculosis whose nucleotide and amino acid sequences could be useful tools in the design of an improved vaccine or a diagnostic method of greater accuracy for tuberculosis. PMID- 1910000 TI - Inhibition of Ehrlichia risticii infection in murine peritoneal macrophages by gamma interferon, a calcium ionophore, and concanavalin A. AB - Ehrlichia risticii incubated with mouse peritoneal macrophages elicited with thioglycolate broth survived and replicated, thereby allowing examination of the effects of several immunopotentiating agents. Treatment of the macrophages with recombinant murine gamma interferon (rMuIFN-gamma) in vitro at 1 day before or 3 h after infection made the macrophages resistant to infection with E. risticii, and macrophages treated with rMuIFN-gamma at 1 to 3 days after infection developed the capacity to eradicate intracellular E. risticii. Similar effects were seen with macrophages treated with the Ca2+ ionophore A23187 before or after E. risticii infection in vitro. Concanavalin A treatment before or 3 h after infection caused the macrophages to become resistant to infection with E. risticii but could confer neither ehrlichiacidal nor ehrlichiastic activity to them once infection had been established for more than 1 day. Bacterial products such as lipopolysaccharide and muramyl dipeptide were less or not at all effective, respectively, in conferring antiehrlichial activity to macrophages. Finally, protein kinase C activator, phorbol myristate acetate, and recombinant tumor necrosis factor did not induce any antiehrlichial activity in macrophages when the macrophages were treated either before or after infection. PMID- 1910001 TI - Intercellular spread of Shigella flexneri through a monolayer mediated by membranous protrusions and associated with reorganization of the cytoskeletal protein vinculin. AB - The spread of Shigella flexneri in a monolayer of infected Henle and HeLa cells was studied by using immunofluorescence and electron microscopy. Infected cells produced numerous bacterium-containing membranous protrusions up to 18 microns in length that penetrated adjacent cells and were subsequently phagocytosed. Fluorescence staining of actin and vinculin in infected cells with phalloidin and monoclonal antibody to vinculin, respectively, demonstrated that the protrusions containing the bacteria consisted of these cytoskeletal proteins. Actin accumulated predominantly at the poles of bacteria distal to the tip of protrusions and appeared as trails extending back towards the host cell cytoplasm. Vinculin, however, was distributed uniformly around the bacteria and throughout the protrusion. A profound rearrangement of vinculin occurred in Henle and HeLa cells following infection with shigellae: whereas in uninfected cells it was distributed mainly around the cell periphery, in infected cells it concentrated mainly around clusters of bacteria in the cytoplasm. This suggests a possible involvement of the vinculin cytoskeletal protein in the intercellular spread of shigellae during an infection. PMID- 1910002 TI - Contribution of individual toxin components to virulence of Bacillus anthracis. AB - Three proteins, protective antigen (PA), lethal factor (LF), and edema factor (EF; a calmodulin-dependent adenylate cyclase), compose the lethal (PA + LF) and edema (PA + EF) toxins secreted by Bacillus anthracis. Mutant strains, each deficient in the production of one toxin component, were constructed, and their virulence was then studied. A kanamycin resistance cassette was inserted in each cya (encoding EF) and lef (encoding LF) gene, and the constructs were separately introduced into B. anthracis Sterne on a mobilizable shuttle plasmid. An EF- strain and an LF- strain were then isolated after homologous recombination with the resident toxin-encoding plasmid, pXO1. Spores from these mutants and from a previously constructed PA- mutant were used to inoculate mice, and the lethality and local edema formation were monitored. LF- or PA- mutants were not lethal even at high inocula, whereas the EF- mutant induced lethal infections. This indicates that LF in combination with PA is a key virulence factor required for lethality. Skin edema formation was observed with the LF- mutant, which produces only the combination of PA and EF. However, EF- and LF- mutants were significantly less efficient at inducing, respectively, lethality and edema than was the parental Sterne strain. These results suggest that the three toxin components might act synergistically in vivo to cause lethality and edema formation. PMID- 1910003 TI - Gamma interferon production in endotoxin-responder and -nonresponder mice during infection. AB - The production of gamma interferon (IFN-gamma) in response to infection and to a number of other agents was compared in Lpsn (C3H/HeN and C57BL/10ScSn) and Lpsd (C3H/HeJ and C57BL/10ScCr) mouse strains. Large differences in IFN-gamma production were observed between C57BL/10ScCr mice and the other mouse strains. With the exception of C57BL/10ScCr, all mouse strains, including C3H/HeJ, exhibited transient levels of IFN-gamma during infection with Salmonella typhimurium. Spleen cells of these mice, explanted on day 3 of infection, produced in vitro IFN-gamma spontaneously; this production was enhanced considerably by heat-killed S. typhimurium, heat-killed Propionibacterium acnes, concanavalin A (ConA), or lipopolysaccharide (LPS). These stimuli, except for LPS, also induced IFN-gamma production in cultures of normal spleen cells from noninfected animals. In contrast, C57BL/10ScCr mice produced no IFN-gamma following infection with S. typhimurium. Also, spleen cells of these mice, explanted on day 3 of infection, exhibited no spontaneous IFN-gamma production. A marginal response was obtained by additional stimulation of the cells with killed S. typhimurium, and a moderate response was obtained with ConA. Normal spleen cells from noninfected C57BL/10ScCr mice showed no IFN-gamma response to killed S. typhimurium, killed P. acnes, or LPS and only a low response to ConA. Impaired IFN-gamma production in C57BL/10ScCr mice was also evident during infection with Plasmodium chabaudi chabaudi, with which a low IFN-gamma response was seen only occasionally. Also, spleen cells from infected animals (days 2 to 8 after infection) exhibited only a very low level of IFN-gamma production in vitro; however, this production could be enhanced further by ConA. In comparison, C57BL/10ScSn mice infected with P. chabaudi chabaudi produced significant amounts of IFN-gamma. Spleen cells explanted from infected animals produced IFN-gamma spontaneously in vitro; this production was enhanced further by killed P. acnes and ConA. The results showed that in addition to the defect in LPS responsiveness, C57BL/10ScCr mice possess a defect in IFN-gamma production in response to different stimuli. During infection, IFN-gamma production and sensitization to LPS occurred in parallel. Infected Lpsn mice exhibited enhanced sensitivity and infected Lpsd C3H/HeJ mice exhibited reasonable sensitivity to the lethal effects of LPS. Lpsd C57BL/10ScCr mice remained resistant to LPS when infected with S. typhimurium and exhibited only marginal sensitivity when infected with P. chabaudi chabaudi. PMID- 1910004 TI - Interaction of a salivary mucin-secretory immunoglobulin A complex with mucosal pathogens. AB - This study examined the interaction of a human salivary low-molecular-weight mucin (MG2) with Staphylococcus aureus and Pseudomonas aeruginosa by using both solution-phase and solid-phase assays. In solution phase, MG2 in human submandibular-sublingual saliva (HSMSL) bound to the bacterial surface; however, the highly purified mucin isoforms (MG2a and MG2b) did not. Mucin binding appeared to be dependent on heterotypic complexing between MG2 and secretory immunoglobulin A (IgA), although other salivary molecules may also be involved. In contrast, in a solid-phase assay in which HSMSL, MG2-containing fractions with secretory IgA, and purified MG2 were immobilized onto a solid surface, there was minimal adherence of S. aureus. The collective results suggest that mucin binding to S. aureus and P. aeruginosa may be predicated on the formation of an MG2 secretory IgA complex. Such interactions may facilitate microbial clearance from the oral cavity and play an important role in preventing colonization of the oral cavity and the respiratory tract by potential pathogens. PMID- 1910005 TI - In vitro study of contact-mediated killing of Candida albicans hyphae by activated murine peritoneal macrophages in a serum-free medium. AB - Activated peritoneal macrophages obtained from Listeria-immune mice were demonstrated to kill nonphagocytosable Candida albicans hyphae by contact mediated mechanisms in a serum-free synthetic medium. The actual killing of hyphae was confirmed by a microculture technique utilizing the dimorphic nature of the fungus. The most efficient candidacidal activity was demonstrated by the macrophages obtained from mice first immunized with live Listeria monocytogenes and then elicited with heat-killed L. monocytogenes cells. Resident macrophages from control mice showed only low candidacidal activity against C. albicans hyphae and yeast cells. Direct physical contact appeared to be required for macrophages to efficiently kill oversized C. albicans hyphae. Efficient in vitro killing of hyphae also required relatively high effector/target cell ratios (50 or higher). The contact-mediated candidacidal activity of activated macrophages was not significantly abrogated by oxygen-radical scavengers, suggesting the involvement of oxygen-independent mechanisms. These results suggest that the enhanced nonspecific immunity to candidiasis seen in Listeria-immune hosts can be attributed, at least in part, to activated fungicidal macrophages. The ability of macrophages to detect and destroy both yeast and hyphal C. albicans cells is clearly an important element of the host defense against candidiasis. PMID- 1910006 TI - Minimal oligosaccharide structures required for induction of immune responses against meningococcal immunotype L1, L2, and L3,7,9 lipopolysaccharides determined by using synthetic oligosaccharide-protein conjugates. AB - The 12 types of meningococcal lipopolysaccharide (LPS) (immunotypes) contain immunotype-specific and cross-reactive epitopes situated on the oligosaccharide part of the LPS molecules. To identify useful cross-reactive epitopes and to determine minimal oligosaccharide structures required for the induction of an immune response against the most prevalent immunotypes, L1, L2, and L3,7,9, synthetic as well as native LPS-derived oligosaccharides were conjugated with tetanus toxoid. L3,7,9 phosphoethanolamine (PEA) group-containing oligosaccharide tetanus toxoid conjugates evoked high immunoglobulin G (IgG) antibody levels in rabbits which were detected by an L2-, L3,7,9-, and, depending on the antiserum, L1-specific enzyme-linked immunosorbent assay (ELISA). Inhibition studies revealed that an identical antibody population was detected by L1 and L3,7,9 ELISA, indicating a similar tertiary structure of the inner core oligosaccharide of these two immunotypes. These antibodies recognize PEA group-containing epitopes present on the L1 and L3,7,9 LPS. An L2 PEA group-containing oligosaccharide-tetanus toxoid conjugate elicited L2- and L3,7,9-specific IgG antibodies, but in contrast with the L3,7,9 conjugates, no L1-specific IgG antibodies were evoked. These results indicate that L1 and L2 LPS do not contain cross-reactive epitopes, whereas both L2 and L3,7,9 LPS and L1 and L3,7,9 LPS possess common determinants. Three linear oligosaccharides and one branched oligosaccharide, representing partial structures of the inner core oligosacchardes of meningococcal LPS, were synthesized. Only the branched synthetic oligosaccharide-containing conjugate was able to induce and L1- and L3,7,9-specific immune response, whereas the linear oligosaccharide-protein conjugates evoked L2-specific immune responses. The branched oligosaccharide (beta-D-Glcp(1----4)-[L-alpha-D-Hepp(1----3)]-L-alpha-D-Hepp ) is therefore considered a minimal structure required for the induction of an immune response against L1 and L3,7,9 LPS and part of a cross-reactive epitope between these two immunotypes. For L2-specific immune responses, oligosaccharide structures terminating in beta-D-Glcp(1----4), alpha-D-GlcNAcp(1----2), or L-alpha-D-Hepp(1- --5) are needed. The results suggest that it is possible to prepare an oligosaccharide structure with the ability to evoke an immune response against L1, L2, and L3,7,9 LPS. A feasible structure for such a "hybrid" oligosaccharide is discussed. PMID- 1910007 TI - Dissociated development of T cells mediating delayed-type hypersensitivity and protective T cells against Listeria monocytogenes and their functional difference in lymphokine production. AB - CD4+ T cells mediating both delayed-type hypersensitivity (DTH) and acquired cellular resistance (ACR) were generated in mice after immunization with viable Listeria monocytogenes. In contrast, CD4+ T cells from mice immunized with killed L. monocytogenes in complete Freund's adjuvant were capable of mediating only DTH but not ACR. To determine the functional difference between T cells mediating DTH and T cells mediating ACR, we examined two different populations of T cells for profiles of lymphokine production after stimulation with a specific antigen in vitro. The production of interleukin-2 (IL-2) and IL-3 but not IL-4 was observed in both T cells mediating only DTH and those mediating DTH and ACR. In this respect, both types of T cells could be categorized into the TH1 population, and they produced macrophage chemotactic factor equally well. However, the production of gamma interferon (IFN-gamma) was observed only in T cells capable of mediating both DTH and ACR. This result was confirmed not only by an enzyme immunoassay specific for murine IFN-gamma but also by Northern (RNA) analysis for the detection of IFN-gamma mRNA. These results suggested that the TH1 population may be subdivided further into two distinct subsets and that the ineffectiveness of the killed bacterial vaccine may be partly explained by the dissociated development of T cell function. PMID- 1910008 TI - Physical mapping of virulence-associated genes in Pseudomonas aeruginosa by transverse alternating-field electrophoresis. AB - The relative chromosomal locations of 20 virulence-associated genes in four clinical isolates of Pseudomonas aeruginosa were investigated by using transverse alternating-field electrophoresis. Each strain had a characteristic restriction pattern when digested with either SpeI or DraI and electrophoresed with 15-s pulses. All four strains had restriction fragments that hybridized with each of the gene probes used, although there were variations in fragment size. An SpeI physical map constructed by Ratnaningsih et al. (E. Ratnaningsih, S. Dharmsthiti, V. Krishnapillai, A. Morgan, M. Sinclair, and B. W. Holloway, J. Gen. Microbiol. 136:2351-2357, 1990) for one of these strains, PAO1, was used to identify the location of 11 previously unmapped genes. The physical locations of the remaining genes were found to be consistent with their genetically mapped loci. Whereas phospholipase C and alginate structural and regulatory genes were associated in three separate clusters in the early, middle, and late regions of the chromosome, no virulence cluster was identified. Our data suggest that the pathogenicity of P. aeruginosa results from the gradual acquisition of genes encoding various virulence determinants. PMID- 1910009 TI - Eight lipooligosaccharides of Neisseria meningitidis react with a monoclonal antibody which binds lacto-N-neotetraose (Gal beta 1-4GlcNAc beta 1-3Gal beta 1 4Glc). AB - Eight of 12 serologically different lipooligosaccharides (LOS) of Neisseria meningitidis bound a mouse monoclonal antibody (anti-My-28) that recognizes lacto N-neotetraose (LNnT) (Gal beta 1-4GlcNAc beta 1-3Gal beta 1-4Glc). Among the 12 LOS immunotypes, types 2, 3, 4, 7, 8, and 9 exhibited strong binding; types 5 and 10 were moderate; and types 1, 6, 11, and 12 were negative as measured by enzyme linked immunosorbent assays, immunodot assays, and immunoblot assays. If an LOS showed multiple components by sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis, the antibody-reactive epitope was expressed on the larger major component, of which the molecular weight was estimated to be 4,000 for most types. The expression of the reactive epitope on the LOS was influenced by the growth medium, and the epitope could be masked by sialylation when N. meningitidis was grown in tryptic soy broth. N-Acetyllactosamine inhibited the binding of the antibody to all eight reactive LOS. The antibody binding to a representative LOS was best inhibited by LNnT and next by N-acetyllactosamine but was not inhibited by lacto-N-tetraose (Gal beta 1-3GlcNAc beta 1-3Gal beta 1 4Glc). These results suggest that the LNnT sequence is present in 8 of 12 immunotype LOS. The presence of the LNnT sequence, a structure expressed by a variety of human cells, in the LOS may play a role in the virulence of N. meningitidis by enabling the organism to evade host immune defenses. PMID- 1910010 TI - Host defense against cholera toxin is strongly CD4+ T cell dependent. AB - This study investigates the role of CD4+ T cells in host defense against cholera enterotoxin-induced diarrhea. Antitoxin immunoglobulin A formation and gut protection against cholera toxin (CT) following oral immunizations with CT were evaluated in normal mice and mice that had been depleted of CD4+ T cells by in vivo treatment with specific anti-CD4 monoclonal antibodies. Flow cytometer analysis demonstrated that anti-CD4 monoclonal antibody effectively eliminated CD4+ T cells in the spleen, mesenteric lymph nodes, and Peyer's patches. In contrast, lamina propria lymphocytes demonstrated only some decrease in CD4+ T cell numbers following antibody treatment. However, CD4 expression of individual lamina propria lymphocytes was strongly down-regulated. Depletion of CD4+ T cells performed prior to oral immunization with CT completely inhibited the ability to respond to CT. No antitoxin production, as detected at the single-cell level by the ELISPOT technique, was found in the spleen, mesenteric lymph nodes, or Peyer's patches, nor did we observe serum antitoxin responses in these mice. Control mice demonstrated strong antitoxin responses in all locations following oral immunization with CT. Anti-CD4 antibody treatment also effectively inhibited the antitoxin immunoglobulin A response in the lamina propria to CT as well as blocked the ability to develop gut protection against CT challenge of ligated intestinal loops after oral CT immunization. Thus, in vivo CD4+ T-cell depletion rendered these mice unable to develop protective immunity in the gut following oral immunization with CT. Moreover, CD4+ T-cell depletion effectively inhibited the antitoxin immune response in the gut lamina propria, mesenteric lymph nodes, Peyer's patches, and spleen when performed prior to both priming and booster immunizations with CT. This study clearly demonstrates the requirement of functional CD4+ T cells in the gut immune system for the development of host defense against CT-induced disease. Our data also reinforce the concept of a strong association between gut protection against CT and local production of neutralizing immunoglobulin A antitoxin. PMID- 1910011 TI - Preservation of monocyte effector functions against Mycobacterium avium-M. intracellulare in patients with AIDS. AB - Mycobacterium avium-M. intracellulare is a frequent cause of late disseminated infection in patients with AIDS. The ability of human peripheral blood monocytes to phagocytose and kill M. avium was examined in an in vitro model. Monocytes were obtained from 13 healthy volunteers and 11 patients with AIDS, three of whom had documented disseminated M. avium infection. Monocytes were precultured for 2 days before infection with two AIDS-associated and two non-AIDS-associated strains of M. avium. Uptake of M. avium as measured by counting intracellular acid-fast bacilli did not differ among healthy subjects, patients with AIDS, or patients with AIDS and previously documented disseminated M. avium infection. Intracellular growth of M. avium was examined by a CFU assay of cell lysates from M. avium-infected monocytes after 0, 4, and 7 days of culture. Intracellular growth inhibition of M. avium at 7 days after infection was comparable between patients with AIDS and healthy donors for all M. avium strains tested. The effects of the addition of recombinant gamma interferon on M. avium uptake and intracellular growth in monocytes also were studied. Pretreatment of monocytes with gamma interferon prior to infection suppressed monocyte phagocytosis of M. avium. Continuously coculturing of monocytes with gamma interferon after infection augmented killing of M. avium among both patients with AIDS and healthy controls for three of the four strains of M. avium tested. The magnitude of this effect, however, was variable from donor to donor and strain to strain. No significant differences were noted between the growth-inhibiting abilities of gamma-interferon-treated monocytes obtained from healthy volunteers and those obtained from patients with AIDS. PMID- 1910012 TI - Cytokine response by human monocytes to Clostridium difficile toxin A and toxin B. AB - Clostridium difficile toxins A and B isolated from strain VPI 10463 were tested for induction of cytokine release by human monocytes. Toxin B at 10(-12) M activated human monocytes as measured by release of interleukin-1 (IL-1), tumor necrosis factor (TNF), or IL-6. These effects of toxin B were heat labile (51 degrees C, 30 min). Toxin B was as effective as bacterial lipopolysaccharides in inducing IL-1 beta but less effective in inducing TNF or IL-6. Toxin B and lipopolysaccharides were synergistic in induction of IL-1 beta, TNF, and IL-6. The toxin A preparation used was 1,000-fold less active than toxin B. Apart from the difference in activity, the two toxins showed identical patterns of reaction and there was no synergism between them. A short pulse with toxin B was sufficient to trigger IL-1 release. Toxin B was also extremely toxic for monocytes. The toxicity and the induced proinflammatory monokines (IL-1 and TNF) may contribute to the pathogenic mechanisms of C. difficile infection and pseudomembranous colitis. PMID- 1910013 TI - Influence of major histocompatibility complex haplotype on the mitogenic response of T cells to staphylococcal enterotoxin B. AB - The abilities of antigen-presenting cells (APC) from nine independent major histocompatibility complex haplotypes and a number of intra-H-2 recombinant congenic strains of mice to present staphylococcal enterotoxin B (SEB) and induce proliferation in murine T-cell receptor V beta 8+ T-cell clones were compared. SEB presented by APC of all haplotypes tested induced significant responses in each of the T-cell clones. The magnitude of response was similar for most haplotypes, but there were limited quantitative differences between certain haplotypes. SEB presented by APC from H-2b mice as well as the intra-H-2 recombinant strains B10.GD and B10.A(4R), which do not express cell surface I-E (designated I-E-), induced the poorest T-cell responses. However, APC from AfE-, AsE-, and AqE- mice were as potent in SEB presentation as APC expressing both I-A and I-E. Antibodies against I-E were more effective than anti-I-A antibodies at inhibiting responses to SEB presented by APC expressing both I-A and I-E, whereas responses induced by APC expressing I-A but not I-E were blocked by antibodies against I-A. Thus, our results show that I-A can present SEB efficiently but that expression of both I-A and I-E on the same APC results in presentation of SEB predominantly by I-E. In addition, experiments using four distinct I-E- strains of mice indicate that I-A alleles differ in their ability to present SEB. PMID- 1910014 TI - Characterization of the C3 gene of Clostridium botulinum types C and D and its expression in Escherichia coli. AB - Clostridium botulinum type C and D strains produce exoenzyme C3, which ADP ribosylates the Rho protein, a 21-kDa regulatory GTP-binding protein. In a previous work, we demonstrated that the C3 gene is encoded by bacteriophages C and D of C. botulinum by using DNA-DNA hybridizations with oligonucleotides deduced from the C3 protein N-terminal sequence. The C3 coding gene was cloned and sequenced, but its upstream DNA region could not be studied because of its instability in Escherichia coli. In this work, the upstream DNA region of the C3 gene was directly amplified by the polymerase chain reaction and sequenced. The C3 gene encodes a polypeptide of 251 amino acids (27,823 Da) consisting of a 40 amino-acid signal peptide and a mature protein of 211 amino acids (23,546 Da). The C3 mature protein was expressed in E. coli under the control of the trc promoter. The recombinant polypeptide obtained was recognized by C3 antibodies and ADP-ribosylated the Rho protein. The C3 gene nucleotide sequence is identical on C and D phage DNAs. At the amino acid sequence level, no similarity was found among C3, other ADP-ribosylating toxins, or tetanus or botulinal A, C1, and D neurotoxins. PMID- 1910015 TI - Pyochelin-mediated iron transport in Pseudomonas aeruginosa: involvement of a high-molecular-mass outer membrane protein. AB - An iron-regulated outer membrane protein of 75,000 daltons was strongly expressed following iron limitation of strains of Pseudomonas aeruginosa which fail to produce pyoverdine. A mutant nonderepressible for this protein (K372) was deficient in pyochelin-mediated iron transport at 150 nM FeCl3, consistent with a role for the 75-kDa protein in ferripyochelin transport. Moreover, ferripyochelin specifically protected the 75-kDa protein against trypsin digestion, supporting an interaction between ferripyochelin and the 75-kDa protein. Previous reports implicated a 14,000-dalton outer membrane protein as the receptor for ferripyochelin (P.A. Sokol and D.E. Woods, Infect. Immun. 40:665-669, 1983) and demonstrated that a mutant (FBP-28) expressing a defective 14-kDa outer membrane protein did not exhibit pyochelin-mediated iron transport (P.A. Sokol, J. Bacteriol. 169:3365-3368, 1987). Nonetheless, we were able to demonstrate (i) that FBP-28 was inducible for the 75-kDa protein under iron-limiting conditions and (ii) that concomitant with the induction of this protein in FBP-28, pyochelin mediated iron uptake at 150 nM FeCl3 was observed. Interestingly, strain K372 did transport ferripyochelin at higher (750 nM) FeCl3 concentrations, suggesting that a second pyochelin-mediated iron transport system, perhaps involving the 14-kDa outer membrane protein identified previously, operates in P. aeruginosa. PMID- 1910016 TI - Immunologic mediators as parameters of the reaction to strenuous exercise. AB - Both the unspecific and the specific branch of the immune system are triggered and governed by contact and by a set of cytokines, including interleukin-1 (IL 1), interleukin-6 (IL-6), and tumor necrosis factor (TNF). These mediators, which are produced by activated macrophages and other cells, have also multiple (pleiotropic) effects on different cells and organs. While TNF and IL-1 have strongly proinflammatory effects and seem to play a critical role in clinical situations such as septic shock, IL-6 has more restorative effects by being the main inducer of the acute phase response of the liver. The monokines also induce fever and release of ACTH in the brain. Strenuous exercise leads to a significant elevation of cytokines in the serum thereby eliciting an acute phase response. Analysis of systemic cytokines in the serum of marathon runners by the 7TD1 cell line assay revealed that the observed activity is very likely IL-6. PMID- 1910017 TI - Vaccination in murine schistosomiasis with adult worm-derived antigens: variables influencing protection in outbred mice. AB - Previous studies have shown that both permissive (mouse) and partially permissive (rabbit) hosts develop high levels of resistance against Schistosoma mansoni infection after vaccination with a multiple antigen extract (SE) obtained by incubation of living adult worms in saline, plus bacterial adjuvant. To investigate variables influencing SE-induced protection in murine schistosomiasis, a series of distinct vaccination protocols were performed focussing on the immunization dose, carrier systems, route, site and amplitude of challenge infection, and time between immunization and challenge. In addition, a new approach was adopted to evaluate SE protective activity, by means of population analysis of worm burden frequency distributions in a large scale study of vaccination in outbred Swiss mice. Distinct curves of frequency and a drastic difference in worm burden distribution of frequencies from SE-vaccinated x non vaccinated mice were found. It was shown that SE could generate 75% mean protection in outbred mice even in the absence of adjuvant. In addition SE immunization was also able to induce full protection against lethal infection. SE induced protection could be modulated by such parameters as dose of SE immunization/challenge interval, and route of cercariae injection. These data show that SE yields very high protective activity in outbred mice, and may provide a further insight for rational design of a vaccine in experimental schistosomiasis. PMID- 1910018 TI - Transesterification of Moz-Asn-Leu-Gly-OEt in methanol. Confirmation of Ca2+ mediated catalysis. AB - During the recrystallization of the crude protected tripeptide ester Moz-Asn-Leu Gly-OEt (obtained by an enzymatic coupling reaction) in methanol/water, the transesterification of this compound to methyl ester was observed. The involvement of Ca2+ in this process was indicated by the results obtained in the following experiments: 1) incubation of crude Moz-Asn-Leu-Gly-OEt in methanol solutions of o-phenanthroline and EDTA; 2) recrystallization of the crude Moz-Asn Leu-Gly-OEt in ethanol/water followed by incubation in methanol; 3) determination of the Ca2+ content of the crude Moz-Asn-Leu-Gly-OEt. After recrystallization Moz Asn-Leu-Gly-OEt lost the ability to be transesterified in methanol. However, in the presence of crude Moz-Asn-Leu-Gly-OEt, or calcium acetate, or a mixture of calcium chloride/sodium acetate, the compound was transesterified, suggesting that the transesterification of crude and recrystallized compounds occurs through different mechanisms. On the basis of these results, and of the conformational data obtained for these peptides by 1H-NMR, we suggest models for the transesterification reactions. PMID- 1910019 TI - Effect of nitroglycerin ointment placement on headache and flushing in healthy subjects. AB - The purpose of this study was to determine the effect of site of nitroglycerin ointment placement on headache and flushing in healthy subjects. Twenty-six subjects were given two doses of nitroglycerin ointment 3 hr apart in a randomly assigned arm-chest sequence or chest-arm sequence. Subject reports of headache and flushing using the visual analogue scale were recorded. There were no significant differences in headache or flushing based on the site or sequence of placement. Thus, the practice by nurses of routinely teaching patients to vary the site of nitroglycerin ointment placement to minimize side-effects must be questioned. PMID- 1910020 TI - Gamma-interferon effects on human fibroblasts from Tenon's capsule. AB - Gamma-interferon (G-IFN) exhibits antiproliferative effects, inhibits collagen synthesis by fibroblasts, and may help to regulate the turnover of fibrous tissue. Fibroblasts from Tenon's capsule are cellular components that contribute to unsuccessful glaucoma filtration surgery. Therefore, the authors studied the effects of G-IFN on growth, wound closure, collagen synthesis, and extracellular matrix in cultured human Tenon's capsule fibroblasts (HTCF). HTCF incubated with G-IFN at doses of 1 to 1000 U/ml showed cellular heterogeneity, with some cells showing morphologic changes characteristic of senescence, and a dose-dependent inhibition of wound closure. At 1000 U/ml, G-IFN reduced collagen synthesis by 57%, reduced immunofluorescent staining of collagen type I and fibronectin network, and altered the organization of actin microfilaments into large cable like structures. Cell proliferation and viability were not affected at any concentration of G-IFN. These results suggest that G-IFN may be useful to modulate wound healing after filtration surgery. PMID- 1910021 TI - Cholestasis in a neonatal intensive care unit. AB - A retrospective study of 17 babies admitted to the neonatal intensive care unit of the Royal Maternity Hospital, Belfast, was undertaken to determine the causes and prognosis of conjugated hyperbilirubinaemia (direct fraction greater than 20% of total) over a five year period. Mean gestational age was 29 weeks and mean birth weight was 1,240g with a 2:1 male preponderance. All babies had a complicated clinical course involving prolonged periods of parenteral nutrition and many episodes of sepsis. Liver damage was not found to be a contributory factor to death in any baby who died before the age of one year. Bilirubin levels in the survivors had returned to normal within one year. No permanent pathological cause of cholestasis, such as biliary atresia, was ascribable to any of the cases, indicating that extensive investigation to exclude anatomical causes in this population is unlikely to prove rewarding. PMID- 1910022 TI - Audit of hyperthyroxinaemia and thyrotoxicosis using a sensitive TSH assay. AB - The aim of this study was determine (a) the causes of hyperthyroxinaemia and (b) the biochemical profile of thyrotoxicosis in a general hospital laboratory for one year using a sensitive TSH assay. Total T4 (TT4) and TSH were measured in all 8,382 samples and TT3, free T4, free T3 and thyroxine binding globulin (TBG) in selected cases. TT4 was elevated in 215 (2.6%). 159 (74%) were due to thyrotoxicosis; 41 (19%) to elevated TBG and 15 (7%) non-thyroidal illness. Thyrotoxicosis (serum TSH less than 0.15m U/1) occurred in 223 (2.7%) of all patients and was diagnosed with high TT4 in 159 (71%), normal due to intercurrent illness. 352 (4%) patients had suppressed TSH while all thyroid hormone values were normal. Thus TT4 may be elevated from causes other than thyrotoxicosis sufficiently frequently to necessitate routine TSH measurements. While Normal TSH measurements nearly always excludes thyrotoxicosis, suppressed values are insufficient to establish a diagnosis or monitor thyroxine replacement therapy. PMID- 1910023 TI - Thrombolytic therapy: then and now. AB - Although thrombolytic agents were discovered nearly 60 years ago, it is only within the past decade that the clinical use of these agents has revolutionized the treatment of acute myocardial infarction. There are four currently available agents approved for use in treatment of myocardial infarction: streptokinase, urokinase, tissue plasminogen activator, and anistreplase. Although each of these agents works in a unique fashion, the common end point of therapy is the dissolution of a fibrin clot by the conversion of plasminogen to plasmin. A number of clinically measurable end points have been used to determine the effectiveness of these agents in the treatment of acute myocardial infarction, including mortality, reperfusion, patency, left ventricular function, left ventricular volumes, and quantitative creatine kinase isoenzyme analysis. Secondary end points have included bleeding and stroke, as well as recurrent ischemic events. Numerous clinical studies have demonstrated the effectiveness of all of these agents in achieving the desired end points and comparative studies, including several large-scale trials, have failed to differentiate among these agents with regard to efficacy. Newer dosing regimens for currently available thrombolytic agents, as well as new thrombolytic agents, are currently under active investigation and will be the subject of intense research over the next few years. Despite the lack of consensus as to which agent is superior, it is clear that thrombolytic therapy for acute myocardial infarction is the treatment of choice. PMID- 1910024 TI - Parathyroid tumors in atomic bomb survivors in Hiroshima: epidemiological study from registered cases at Hiroshima Prefecture Tumor Tissue Registry, 1974-1987. AB - An examination of registered cases of parathyroid tumor in Hiroshima Prefecture between 1974 and 1987 revealed 23 cases. An epidemiological study showed that the incidence of parathyroid tumors in Hiroshima Prefecture was significantly higher in the total exposed, especially among the proximally exposed (within 2,000 m from the hypocenter), than in the control nonexposed group (P less than 0.001). A similar trend was seen for parathyroid tumor associated with primary hyperparathyroidism. PMID- 1910025 TI - Co-production of interleukin-1 and interleukin-6 in tumor cell lines elaborating colony-stimulating factors. AB - Six carcinoma cell lines elaborating colony-stimulating factors (CSFs) were examined by enzyme-linked immunosorbent assay and Northern blotting to determine whether or not they co-produced interleukin-1 alpha (IL-1 alpha), IL-1 beta and IL-6. All 6 cell lines were co-producers; IL-1 alpha was produced in all 6, IL-6 in 5 and IL-1 beta in 3 of them. These results indicate that IL-1 and IL-6 are commonly co-produced in CSF-producing tumors. PMID- 1910026 TI - Familial aggregation of cancer from proband cases with childhood adrenal cortical carcinoma. AB - Family pedigree of Li-Fraumeni syndrome was investigated from probands with childhood adrenocortical carcinoma in Japan. From 47 probands, 7 families had 3 or more cancer cases at ages less than 45 years within the first generation; one satisfied Li's original criteria, two were acceptable because of multiple primary cancer in the probands, and others showed an aggregation of cancers with onsets at early ages, though no sarcoma of mesenchymal origin was found. A significantly higher occurrence of cancer in the mothers of the probands, especially of the breast, was consistent with reports from the USA, and liver cancer, osteosarcoma and lung cancer among family members under the age of 45 also showed a higher frequency than in the general population. Similarities and differences between Japanese and Caucasian cases are discussed. PMID- 1910027 TI - Proline is required for transcriptional control of the aromatic hydrocarbon inducible P(1)450 gene in C57BL/6 mouse monolayer-cultured hepatocytes. AB - Expression of aryl hydrocarbon hydroxylase (AHH) and the corresponding gene, Cyp1A1, or P(1)450 in mice, in C57BL/6 mouse hepatocytes in primary culture was investigated after exposure to benz[a]-anthracene with respect to proline-related metabolic regulation. When the cells were cultivated in complete Waymouth MB752/1 (Way), prominent induction of AHH by benz[a]anthracene was observed, whereas the induction was inefficient in the same but proline-deficient medium [Way-(-pro)]. Constitutive AHH activities decreased with increasing culture period. P(1)450 gene transcripts were slightly expressed when the medium was changed, independently of whether the cells were cultivated in either Way or Way(-pro), followed by decreased within 24 h and no apparent induction of AHH. However, treatment with delta 1-pyrroline-5-carboxylic acid (P5C), a biosynthetic precursor for proline, dose-dependently increased basal AHH activities in the cells cultivated in Way-(-pro). Benz[a]anthracene induction of AHH in cells cultivated in Way(-pro) was additively increased in the presence of P5C as much as with proline. Treatment with o-aminobenzaldehyde, which inactivates P5C, drastically reduced the induced AHH activities in hepatocytes cultivated in either P5C-added Way(-pro) or Way medium. Benz[a]anthracene induced both P(1)450 and P(3)450 mRNAs. Neither proline nor P5C increased the induced transcripts within 12 h after the start of benz[a]-anthracene treatment, but the two compounds increased the amounts of P(1)450 mRNA found at later time points. After treatment with actinomycin D, the half-life of the induced P(1)450 mRNA was approximately 12 h, being independent of the presence of either proline or P5C. Our observations suggest that induction of AHH after treatment with polycyclic aromatic hydrocarbon is dependent on proline-related metabolism which influences the transcriptional process of P(1)450 gene expression. PMID- 1910028 TI - Accumulation of p60lck in HTLV-I-transformed T cell lines detected by an anti-lck monoclonal antibody, MOL 171. AB - The lck gene encodes a protein tyrosine kinase of nonreceptor type, p56lck, whose expression occurs almost exclusively in T lymphocytes. MOL 171, an anti-p56lck monoclonal antibody, was produced by using a 25-amino-acid synthetic polypeptide as the antigen, its structure corresponding to the N-terminal region deduced from the lck cDNA sequence. Immunoblot analysis with MOL 171 showed the accumulation of 60 kD form of Lck protein, p60lck, and the decrease of p56lck in human T cell leukemia virus type I (HTLV-I)-transformed T cell lines. Another anti-Lck monoclonal antibody, MOL 294, raised by using a synthetic peptide corresponding to the C-terminal region deduced from the lck cDNA sequence, also detected the accumulation of p60lck in those HTLV-I-transformed T cell lines. The appearance of p60lck with the decrease of p56lck in normal T lymphocytes after stimulation suggested the origin of p60lck in HTLV-I-transformed T cells. PMID- 1910029 TI - Abnormal expression of blood group-related antigens in uterine endometrial cancers. AB - The expression of A, B, and H group antigens, Lewis group antigens (Lewis(a), Lewis(b), Lewis(x), and Lewis(y)), and Lc4 and nLc4 antigens, the precursor antigens of both groups, was examined immunohistochemically with monoclonal antibodies in 9 normal endometria, 6 endometrial hyperplasias, and 31 endometrial cancers. 1) A, B and/or H antigens were detected in endometrial cancers at an incidence of 51.6%, while no distinct localization of these antigens was observed in normal endometria. H antigen, the precursor of A and B antigens, was particularly frequently detected in endometrial cancers. 2) An increased rate of expression of Lewis group antigens, particularly Lewis(b) antigen, was observed in endometrial cancers compared with its expression in normal endometria. 3) Lc4 and nLc4 antigens were detected in endometrial cancers at rates of 41.9% and 38.7%, respectively, these expressions being increased compared with those in normal endometria. 4) These results suggest that a highly abnormal expression of blood group-related antigens in endometrial cancers occurs not only at the level of A, B, and H antigens and Lewis group antigens, but also at the level of their precursor Lc4 and nLc4 antigens. 5) Lewis(a), Lewis(b), and Lc4 antigens, built on the type-1 chain, are more specific to endometrial cancers than their respective positional isomers, Lewis(x), Lewis(y), and nLc4 antigens, built on the type-2 chain. PMID- 1910030 TI - Enhancement of the antitumor effect of glucose oxidase by combined administration of hydrogen peroxide decomposition inhibitors together with an oxygenated fluorocarbon. AB - Glucose oxidase (GO) catalyzes the conversion of beta-D-glucose and molecular oxygen to D-glucono-delta-lactone and H2O2. H2O2 produced by GO was effective in preventing tumor growth in mice bearing not only ascites tumor but also solid tumor. The effect of GO was enhanced by the combined administration of catalase inhibitors such as 3-aminotriazole, hydroxylamine and sodium azide or the GSH synthesis inhibitor buthionine-(S,R)-sulfoximine in vivo. The cytolytic activity of GO against T-24 cultured cells in vitro was also enhanced by addition of these inhibitors together with GO. In the peritoneal cavity of mice the antitumor effect of GO seemed to be dependent on the amount of oxygen released from oxygenated fluorocarbon-43 (FC-O2), an oxygen-supplying substance. Furthermore, the combined administration of H2O2-decomposing enzyme inhibitors and FC-O2 synergistically enhanced the antitumor effect of GO. These results suggest that GO is suitable for antitumor chemotherapy and that the use of inhibitors of H2O2 decomposing enzymes and FC-O2 potentiated the GO therapy. PMID- 1910031 TI - Antitumor effect of recombinant human interleukin-2 on the growth of murine hemangioendothelioma D14 in nude mice: occurrence of large granular cells in the tumor. AB - The antitumor effect of recombinant human interleukin-2 (rIL-2) on murine hemangioendothelioma D14 (D14) in female BALB/c-nu/nu mice was examined histologically. D14 cells which had been maintained in vitro were transplanted subcutaneously into nude mice on day 0 (1 x 10(7) cells/mouse). The mice with established tumor on day 28 received rIL-2 subcutaneously at a dose of 20 micrograms/mouse/day for 35 days. On day 63, the mice were killed, and the tumor, spleen and bone marrow were examined histologically. In the mice that had received rIL-2, tumor growth was significantly suppressed. Histologically, there was marked infiltration of large granular cells (about 15-30 microns in diameter) in the tumors. In the adjacent areas, there was a significant increase in the number of tumor cells showing karyorrhexis. The large granular cells (LGC) contained periodic acid Schiff-positive round granules in the cytoplasm and were stained positively for Thy-1.2 surface antigen. The LGC were also positive for asialo GM1 surface antigen but not for Lyt-1, Lyt-2 or IgG surface antigens. This evidence suggests that the LGC are lymphokine-activated killer-like cells which were derived from a natural killer cell lineage. The concomitant increases in the number of LGC and the number of cells showing karyorrhexis in the tumors of the mice treated with rIL-2 suggest that LGC play an important role in the destruction of tumor cells. PMID- 1910033 TI - Composition of the enterococcal and streptococcal intestinal flora of poultry. AB - Identification to species level showed that Enterococcus faecalis and Ent. faecium largely dominated the enterococcal and streptococcal gut flora of 1-d-old chicks. Enterococcus faecalis was rare in 3- to 5-week-old broilers. Two species, Ent. faecium and Streptococcus alactolyticus, were isolated from nearly all broilers examined. Enterococcus hirae and Ent. durans were found in the small intestines of this category of poultry. In layers and parent stock of over 12 weeks of age, Ent. cecorum dominated with Strep. alactolyticus ranking next. Other species were isolated irregularly. Enterococcus avium and Ent. gallinarum, originally described from chickens, were rarely found. These species did not appear to belong to the normal intestinal flora of poultry. PMID- 1910032 TI - Comparison of the effects of intravenously bolus-administered endothelin-1 and infused angiotensin II on the subcutaneous tumor blood flow in anesthetized rats. AB - To evaluate the effects of endothelin-1 (ET-1) on tumor blood flow, the authors measured the mean arterial blood pressure (MABP) of enflurane-anesthetized male Donryu rats and the tissue blood flow of subcutaneously implanted tumor (Yoshida rat ascites hepatoma LY-80) by using a hydrogen clearance method. The tumor blood flow was evaluated in terms of the ratio to the maximum blood flow, which was defined as the largest flow in the same position during successive measurements. After bolus intravenous administration of ET-1 (1.0 nmol/kg), MABP reached approximately 140 mmHg (at 5-30 min), diminishing gradually to the baseline level over 2 h. The tumor blood flow increased from 36.7 +/- 20.6 to 59.5 +/- 30.2% (n = 32, P less than 0.001, at 2 min), returning to the baseline level at 10 min. On the other hand, at 2 min after the beginning of continuous intravenous infusion of [Asp1, Ile5]-angiotensin II (AII; the dose was determined by a blood pressure control system for keeping MABP at approximately 150 mmHg, consequently 0.26 micrograms/kg/min on the average), the tumor blood flow increased from 42.3 +/- 21.6 to 76.4 +/- 22.6% (n = 32, P less than 0.001), which was significantly larger than the flow after ET-1. The results indicate that hypertension induced by systemic ET-1 injection is less effective than hypertension induced by continuous systemic AII infusion in increasing tumor blood flow; AII is probably a suitable agent as a safe and effective enhancer of tumor blood flow. Moreover, ET-1 appears to constrict arterial vessels in the microcirculation time dependently, while AII constricts probably only normal peripheral arterioles. PMID- 1910034 TI - Expression of a beta-galactosidase gene from Clostridium acetobutylicum in Lactococcus lactis subsp. lactis. AB - A beta-galactosidase gene from Clostridium acetobutylicum NCIB 2951 was expressed after cloning into pSA3 and electroporation into derivatives of Lactococcus lactis subsp. lactis strains H1 and 7962. When the clostridial gene was introduced into a plasmid-free derivative of the starter-type Lact. lactis subsp. lactis strain H1, the resulting construct had high beta-galactosidase activity but utilized lactose only slightly faster than the recipient. beta-galactosidase activity in the construct decreased by over 50% if the 63 kb Lac plasmid pDI21 was also present with the beta-galactosidase gene. Growth rates of Lac+ H1 and 7962 derivatives were not affected after introduction of the clostridial beta galactosidase, even though beta-galactosidase activity in a 7962 construct was more than double that of the wild-type strain. When pDI21 was electroporated into a plasmid-free variant of strain 7962, the recombinant had high phospho-beta galactosidase activity and a growth rate equal to that of the H1 wild-type strain. The H1 plasmid-free strain grew slowly in T5 complex medium, utilized lactose and contained low phospho-beta-galactosidase activity. We suggest that beta-galactosidase expression can be regulated by the lactose phosphotransferase system-tagatose pathway and that Lact. lactis subsp. lactis strain H1 has an inefficient permease for lactose and contains chromosomally-encoded phospho-beta galactosidase genes. PMID- 1910035 TI - Treatment choice after one antidepressant fails: a survey of northeastern psychiatrists. AB - BACKGROUND: Because limited evidence exists to help clinicians choose the next step after a depressed patient fails to respond to an adequate trial of an antidepressant, I conducted a survey to explore psychiatrists' treatment choices. METHOD: I asked 118 northeastern psychiatrists what they would do next in response to a clinical vignette of an inpatient with DMS-III-R major depression who failed to respond to 4 weeks of nortriptyline at adequate blood levels. RESULTS: Lithium augmentation was chosen by more than a third (33.9%) of psychiatrists. Other choices, in order of decreasing frequency, were continuing nortriptyline for another 2 weeks (17.8%) and switching to either fluoxetine (16.1%), electroconvulsive therapy (11.0%), or a monoamine oxidase inhibitor (6.8%). Only one psychiatrist each chose thyroid augmentation or bupropion. CONCLUSIONS: The surveyed psychiatrists overwhelmingly preferred lithium augmentation over other strategies to manage treatment-resistant depression. Research on comparative strategies is lacking and urgently needed. PMID- 1910036 TI - A novel prenyltransferase for a small GTP-binding protein having a C-terminal Cys Ala-Cys structure. AB - smg p25A/rab3A p25 is a member of the small GTP-binding protein superfamily which is implicated in intracellular vesicle transport. smg p25A has a cDNA-predicted C terminal structure of Cys-Ala-Cys. The protein purified from bovine brain membranes is geranylgeranylated at both the two cysteine residues and carboxyl methylated at the C-terminal cysteine residue. Two types of prenyltransferase for small GTP-binding proteins have thus far been reported: ras p21 farnesyltransferase (ras p21 FT) and rhoA p21 geranylgeranyltransferase (rhoA p21 GGT). Neither of them geranylgeranylated smg p25A having a C-terminal Cys-Ala-Cys structure. In this paper, a smg p25A GGT was partially purified from bovine brain cytosol and separated from the ras p21 FT and rhoA p21 GGT by column chromatographies. smg p25A GGT transferred the geranylgeranyl moiety from geranylgeranyl pyrophosphate to both the two cysteine residues in the C-terminal Cys-Ala-Cys structure of smg p25A. smg p25A GGT did not use farnesyl pyrophosphate as a substrate and was also inactive on c-Ha-ras p21 and rhoA p21 with either farnesyl pyrophosphate or geranylgeranyl pyrophosphate as a substrate. These results indicate that there are at least three types of prenyltransferase for small GTP-binding proteins in mammalian tissues. PMID- 1910037 TI - Rsr1 and Rap1 GTPases are activated by the same GTPase-activating protein and require threonine 65 for their activation. AB - The Rsr1 protein of Saccharomyces cerevisiae has been shown to be essential for bud site selection (Bender, A., and Pringle, J. (1989) Proc. Natl. Acad. Sci. U.S.A. 86, 9976-9980). This protein of 272 amino acids shares approximately 50% sequence identity with both Ras and Rap GTPases. However, neither GTP binding nor GTPase activity of the Rsr1 protein has been reported. The Rsr1 protein shares with human Rap1 GTPases the four specific motifs, i.e. Gly-12, residues 32-40, Ala-59, and residues 64-70, that are required for GAP3-dependent activation of the Rap1 GTPases. In this paper we demonstrate that the intrinsic GTPase activity of the Rsr1 protein is stimulated by GAP3 purified from bovine brain cytosol. The Rsr1 GTPase is not activated by either GAP1 or GAP2 which are specific for the Ras and Rho GTPases, respectively. Thus, it appears that the Rsr1 GTPase is a new member of the Rap1 GTPase family. Replacement of Gly-12 by Val in the Rsr1 GTPase completely abolishes the GAP3-dependent activation. The chimeric GTPases, Ras(1 60)/Rsr1(61-168) and Rsr1(1-65)/Ras(66-189), are activated by GAP3 but not by GAP1. Replacement of Thr-65 by Ser in the latter chimeric GTPase completely abolishes the GAP3-dependent activation, indicating that Thr-65 is required for distinguishing GAP3 from GAP1. We have previously shown that Gln-61 and Ser-65 are sufficient to determine the GAP1 specificity. Replacement of Thr-35 by Ala in the common effector domain (residues 32-40) of the chimeric Ras/Rsr1 GTPases completely abolishes GAP3-dependent activation. PMID- 1910038 TI - Determination of the rate and equilibrium constants for oxygen and carbon monoxide binding to R-state human hemoglobin cross-linked between the alpha subunits at lysine 99. AB - The kinetics of O2 and CO binding to R-state human hemoglobin A0 and human hemoglobin cross-linked between the alpha chains at Lys99 residues were examined using ligand displacement and partial photolysis techniques. Oxygen equilibrium curves were measured by Imai's continuous recording method (Imai, K. (1981) Methods Enzymol. 76, 438-449). The rate of the R to T transition was determined after full laser photolysis of the carbon monoxide derivative by measuring the resultant absorbance changes at an isosbestic point for ligand binding. Chemical cross-linking caused the R-state O2 affinity of alpha subunits to decrease 6-fold compared with unmodified hemoglobin. This inhibition of O2 binding was the result of both a decrease in the rate constant for ligand association and an increase in the rate constant for dissociation. The O2 affinity of R-state beta subunits was reduced 2-fold because of an increase in the O2 dissociation rate constant. These changes were attributed to proximal effects on the R-state hemes as the result of the covalent cross-link between alpha chain G helices. This proximal strain in cross-linked hemoglobin was also expressed as a 5-fold higher rate for the unliganded R to T allosteric transition. The fourth O2 equilibrium binding constant, K4, measured by kinetic techniques, could be used to analyze equilibrium curves for either native or cross-linked hemoglobin. The resultant fitted values of the Adair constants, a1, a2, and a3 were similar to those obtained when K4 was allowed to vary, and the fits were of equal quality. When K4 was fixed to the kinetically determined value, the remaining Adair constants, particularly a3, became better defined. PMID- 1910039 TI - Expression and characterization of a recombinant yeast isoleucyl-tRNA synthetase. AB - We describe the heterologous expression of a recombinant Saccharomyces cerevisiae isoleucyl-tRNA synthetase (IRS) gene in Escherichia coli, as well as the purification and characterization of the recombinant gene product. High level expression of the yeast isoleucyl-tRNA synthetase gene was facilitated by site specific mutagenesis. The putative ribosome-binding site of the yeast IRS gene was made to be the consensus of many highly expressed genes of E. coli. Mutagenesis simultaneously created a unique BclI restriction site such that the gene coding region could be conveniently subcloned as a "cassette." The variant gene was cloned into the expression vector pKK223-3 (Brosius, J., and Holy, A. (1984) Proc. Natl. Acad. Sci. U.S.A. 81, 6929-6933) thereby creating the plasmid pKR4 in which yeast IRS expression is under the control of the isopropyl-thio beta-galactopyranoside (IPTG)-inducible tac promoter. Recombinant yeast IRS, on the order of 10 mg/liter of cell culture, was purified from pKR4-infected and IPTG-induced E. coli strain TG2. Yeast IRS was purified to homogeneity by a combination of anion-exchange and hydroxyapatite gel chromatography. Inhibition of yeast IRS activity by the antibiotic pseudomonic acid A was tested. The yeast IRS enzyme was found to be 10(4) times less sensitive to inhibition by pseudomonic acid A (Ki = 1.5 x 10(-5) M) than the E. coli enzyme. E. coli strain TG2 infected with pKR4, and induced with IPTG, had a plating efficiency of 100% at inhibitor concentrations in excess of 25 micrograms/ml. At the same concentration of pseudomonic acid A, E. coli strain TG2 infected with pKK223-3 had a plating efficiency less than 1%. The ability of yeast IRS to rescue E. coli from pseudomonic acid A suggests that the eukaryotic synthetase has full activity in its prokaryotic host and has specificity for E. coli tRNA(ile). PMID- 1910040 TI - Replacement of lysine 234 affects transition state stabilization in the active site of beta-lactamase TEM1. AB - Lysine 234 is a residue highly conserved in all beta-lactamases, except in the carbenicillin-hydrolyzing enzymes, in which it is replaced by an arginine. Informational suppression has been used to create amino acid substitutions at this position in the broad spectrum Escherichia coli beta-lactamase TEM-1, in order to elucidate the role of this residue which lies on the wall at the closed end of the active site cavity. The mutants K234R and K234T were constructed and their kinetic constants measured. Replacement of lysine 234 by arginine yields an enzyme with similar activity toward cephalosporins and most penicillins, except toward the carboxypenicillins for which the presence of the guanidine group enhances the transition state binding. The removal of the basic group in the mutant K234T yields a protein variant which retains a low activity toward penicillins, but losts drastically its ability to hydrolyze cephalosporins. Moreover, these two mutations largely decreased the affinity of the enzyme for penicillins (10-fold for K234R and 50-fold for K234T). This can be correlated with the disruption of the predicted electrostatic binding between the C3 carboxylic group of penicillins and the amine function of the lysine. Therefore, lysine 234 in the E. coli beta-lactamase TEM-1 is involved both in the initial recognition of the substrate and in transition state stabilization. PMID- 1910041 TI - Regeneration of vitamin E in human platelets. AB - Human platelets possess active lipoxygenase and cyclooxygenase which convert arachidonic acid to (12S)-12-hydroperoxy-5,8,10,14-eicosatetraenoic acid (12 HPETE) plus (12S)-12-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE) and thromboxane B2 plus 12-hydroxy-5,8,10-heptadecatrienoic acid (HHT), respectively. When platelet homogenates were incubated with arachidonate, there was a rapid consumption of platelet tocopherol. Time course analysis revealed that within 0.5 min, over half of arachidonate and tocopherol were metabolized. Mass formation of 12-HPETE and 12-HETE or thromboxane B2 and HHT exceeded that of the mass of tocopherol oxidized. Preincubation with the lipoxygenase inhibitor 5,8,11,14 eicosatetraynoic acid (ETYA) completely abolished this arachidonate-induced tocopherol oxidation whereas cyclooxygenase inhibitors (indomethacin and aspirin) further potentiated tocopherol oxidation, indicating that this oxidation is closely linked with platelet 12-lipoxygenase activity. Incubation with lipoxygenase metabolites of arachidonic acid showed that only 12-HPETE caused a rapid tocopherol oxidation which was followed by a gradual tocopherol regeneration. By using nordihydroguaiaretic acid (NDGA), a lipoxygenase inhibitor which is also a strong reductant, over 60% of the arachidonate-induced oxidized tocopherol was regenerated. Tocopherol regeneration declined with increasing oxidation time induced by arachidonate, and after 30-60 min virtually no regeneration could be observed, suggesting that the precursor molecule was unstable. We postulate that the precursor molecule is the tocopheroxyl radical. In the presence of ETYA, a lipoxygenase inhibitor without antioxidant properties, either ascorbate or GSH provided significant tocopherol regeneration. Kinetic studies showed that tocopherol regeneration after the addition of ascorbate was essentially completed by 1 min. By contrast, GSH addition caused a steady increase in tocopherol which peaked after 10 min of its addition. To determine whether this rapid regeneration is chemical or enzymic, regeneration was studied in the presence of chloroform and methanol. Comparison of various reductants in this denaturing condition for enzymes showed that ascorbate and NDGA afforded significant regeneration whereas GSH was ineffective, indicating that there are distinct enzymic and non-enzymic mechanisms for tocopherol regeneration. This study provides direct evidence from mass analysis that tocopherol can be regenerated in human cell homogenates. This finding implies that maintenance of membrane tocopherol status may be an essential function of ascorbate and GSH which operate in concert to ensure maximum membrane protection against oxidative damage. PMID- 1910042 TI - Altering the mouth of a hydrophobic pocket. Structure and kinetics of human carbonic anhydrase II mutants at residue Val-121. AB - Eleven amino acid substitutions at Val-121 of human carbonic anhydrase II including Gly, Ala, Ser, Leu, Ile, Lys, and Arg, were constructed by site directed mutagenesis. This residue is at the mouth of the hydrophobic pocket in the enzyme active site. The CO2 hydrase activity and the p-nitrophenyl esterase activity of these CAII variants correlate with the hydrophobicity of the residue, suggesting that the hydrophobic character of this residue is important for catalysis. The effects of these mutations on the steady-state kinetics for CO2 hydration occur mainly in kcat/Km and Km, consistent with involvement of this residue in CO2 association. The Val-121----Ala mutant, which exhibits about one third normal CO2 hydrase activity, has been studied by x-ray crystallographic methods. No significant changes in the mutant enzyme conformation are evident relative to the wild-type enzyme. Since Val-121 is at the mouth of the hydrophobic pocket, its substitution by the methyl side chain of alanine makes the pocket mouth significantly wider than that of the wild-type enzyme. Hence, although a moderately wide (and deep) pocket is important for substrate association, a wider mouth to this pocket does not seriously compromise the catalytic approach of CO2 toward nucleophilic zinc-bound hydroxide. PMID- 1910043 TI - Catalytic function of tyrosine residues in para-hydroxybenzoate hydroxylase as determined by the study of site-directed mutants. AB - The role of protein residues in activating the substrate in the reaction catalyzed by the flavoprotein p-hydroxybenzoate hydroxylase was studied. X-ray crystallography (Schreuder, H. A., Prick, P.A.J., Wieringa, R.K., Vriend, G., Wilson, K.S., Hol, W.G. J., and Drenth, J. (1989) J. Mol. Biol. 208, 679-696) indicates that Tyr-201 and Tyr-385 form a hydrogen bond network with the 4-OH of p-hydroxybenzoate. Therefore, site directed mutants were constructed, converting each of these tyrosines into phenylalanines. Spectral (visible and fluorescence) properties, reduction potentials, and binding constants are very similar to those of wild type, indicating that there are no major structural changes in the mutants. In the absence of substrate, the mutants and wild type exhibit similar pH-dependent changes in the FAD spectrum. However, the enzyme-substrate complex of Tyr-201----Phe lacks an ionization observed in both wild type and Tyr-385--- Phe, which preferentially bind the phenolate form of substrates. Tyr-201----Phe shows no preference, indicating that Tyr-201 is required to ionize the substrate. The mutants have less than 6% the activity of the wild type enzyme. The effects on catalysis were studied by stopped flow techniques. Reduction of FAD by NADPH is slower by 10-fold in Tyr-201----Phe and 100-fold in Tyr-385----Phe. When the reduced Tyr-201----Phe-p-hydroxybenzoate complex reacts with oxygen, a long-lived flavin-C(4a)-hydroperoxide is observed, which slowly eliminates H2O2 with very little hydroxylation. Thus, the role of Tyr-201 is to activate the substrate by stabilizing the phenolate. Tyr-385----Phe reacts with oxygen to form 25% oxidized enzyme, and 75% flavin hydroperoxide, which successfully hydroxylates the substrate. This mutant also hydroxylates the product (3, 4-dihydroxybenzoate) to form gallic acid. PMID- 1910044 TI - Increased cytotoxic activity of Pseudomonas exotoxin and two chimeric toxins ending in KDEL. AB - Pseudomonas exotoxin (PE) is a 66,000 molecular weight protein secreted by Pseudomonas aeruginosa. PE is made up of three domains, and PE40 is a form of PE which lacks domain Ia (amino acids 1-252) and has very low cytotoxicity because it cannot bind to target cells. The sequence Arg-Glu-Asp-Leu-Lys (REDLK) at the carboxyl terminus of Pseudomonas exotoxin has been shown to be important for its cytotoxic activity (Chaudhary, V. K., Jinno, Y., FitzGerald, D. J., and Pastan, I. (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 308-312). In this study, we tested the effect of altering the carboxyl sequence of PE from REDLK to the characteristic endoplasmic reticulum retention sequence, KDEL, or to KDEL repeated three times (KDEL)3. We also made similar changes at the carboxyl terminus of two chimeric toxins in which domain I of PE (amino acids 1-252) was either replaced with transforming growth factor alpha (TGF alpha) to make TGF alpha-PE40 or with a single chain antibody (anti-Tac) reacting with the human interleukin 2 receptor to make anti-Tac(Fv)-PE40. Statistical analyses of our results demonstrate that PE and its derivatives ending in KDEL or (KDEL)3 are significantly more active than PE or derivatives ending in REDLK. We have also found that brefeldin A, which is known to perturb the endoplasmic reticulum, inhibits the cytotoxic action of PE. Our results suggest that the altered carboxyl terminus may enable the toxin to interact more efficiently with a cellular component involved in translocation of the toxin to the cytosol. PMID- 1910045 TI - Induction of immediate early genes by Ca2+ influx requires cAMP-dependent protein kinase in PC12 cells. AB - Agents that activate cAMP-dependent protein kinase (PKA) as well as agents that increase intracellular calcium induce the expression of certain immediate early genes (IEGs). Recently, it has been demonstrated that the same cis-acting element in the 5' region of the c-fos gene has the ability to mediate both cAMP- and calcium-induced c-fos expression in PC12 cells (Sheng, M., McFadden, G., and Greenberg, M. (1990) Neuron 4, 571-582). Here we demonstrate that both cAMP- and calcium-mediated induction of c-fos and egr1 are dependent on PKA activity. Addition of either depolarizing concentrations of KCl or the calcium ionophore, ionomycin, to PC12 cells increased the expression of both c-fos and egr1, but these inductions were dramatically reduced in three PKA-deficient cell lines, 123.7, AB.11, and A126-1B2. Furthermore, pretreatment of PC12 cells with 20 microM H89, a specific inhibitor of PKA, inhibited forskolin, dibutyryl cAMP, and KCl-induced c-fos and egr1 induction, while having no effect on NGF induction. Likewise, in the PKA-deficient cells, NGF or an activator of protein kinase C induced c-fos and egr1 normally. To determine if PKA deficiency modifies the ability of Ca2+ to activate calcium-dependent kinases, autophosphorylation of multifunctional Ca2+/calmodulin-dependent protein kinase (CaM kinase) in response to Ca2+ influx was determined. In parental PC12 cells, PC12 cells pretreated with H89, and PKA-deficient cell lines, CaM kinase was activated equivalently in response to KCl depolarization. These results suggest that PKA is not required for Ca(2+)-induced increase in CaM kinase activity and that the induction of IEGs in response to Ca2+ influx is PKA-dependent. Thus, the requirement for PKA resides at a point distal to the activation of calmodulin-dependent processes. PMID- 1910046 TI - Tyrosine kinase-defective insulin receptors undergo insulin-induced microaggregation but do not concentrate in coated pits. AB - Biologically active colloid-gold complexes were used to compare ligand-induced microaggregation, redistribution, and internalization of insulin receptors on Rat 1 fibroblasts expressing wild type (HIRc) or tyrosine kinase-defective (HIR A/K1018) human insulin receptors. Insulin-like growth factor I (IGF I) and alpha 2-macroglobulin receptors also were compared. On both cell types, all four unoccupied receptor types occurred predominantly as single receptors. Ligand binding caused receptor microaggregation. Microaggregation of wild type or kinase defective insulin receptors or IGF I receptors was not different. alpha 2 Macroglobulin receptors formed larger microaggregates. Compared to wild type insulin or IGF I receptors, accumulation of kinase-defective insulin receptor microaggregates in endocytic structures was decreased, and the size of microaggregates in coated pits was significantly smaller. As a result, receptor mediated internalization of gold-insulin by HIR A/K1018 cells was less than 6% of the cell-associated particles compared to approximately 60% of the particles in HIRc cells. On HIR A/K1018 cells, alpha 2-macroglobulin and IGF I were internalized via coated pits demonstrating that those structures were functional. These results suggest that: 1) ATP binding, receptor autophosphorylation, and activation of receptor kinase activity are not required for receptor microaggregation; 2) receptor microaggregation per se is not sufficient to cause ligand-induced receptor-mediated internalization or the biological effects of insulin; and 3) autophosphorylation of the beta-subunit or activation of the receptor kinase activity is required for the insulin-induced concentration of occupied receptors in coated pits. PMID- 1910047 TI - Identification of low molecular weight GTP-binding proteins and their sites of interaction in subcellular fractions from skeletal muscle. AB - The presence of low molecular weight GTP-binding proteins was investigated in subcellular fractions from skeletal muscle. Skeletal muscle homogenate, transverse tubules, triads, sarcoplasmic reticulum membranes, and cytosol fractions were separated in sodium dodecyl sulfate-gel electrophoresis and blotted onto nitrocellulose. The presence of GTP-binding proteins was explored by incubation of these blots with [alpha-32P] GTP. GTP labeled two polypeptides of Mr = 23,000 and 29,000 in all the fractions examined. Binding of [alpha-32P]GTP was specific and dependent on Mg2+. The 23-kDa polypeptide was labeled to a higher extent with [alpha-32P]GTP than the 29-kDa polypeptide, although both were enriched in transverse tubule fractions. A GTP-binding polypeptide of 40 kDa was also enriched in transverse tubule preparations and identified as Gi alpha by immunostaining with anti-Gi alpha. Using a blot overlay approach and [alpha 32P]GTP-labeled cytosolic components, several polypeptides were identified that interact with the 23- and 29-kDa GTP-binding proteins. Among these components were polypeptides of Mr = 60,000, 47,000, 44,000, 42,000, and 38,000, which were mainly of cytosolic origin but also associated with triads and transverse tubule membranes. The 47-, 44-, 42-, and 38-kDa polypeptides were found to be structurally related to the glycolytic enzymes enolase, 3-phosphoglyceric phosphokinase, aldolase, and glycoeraldehyde-3-phosphate dehydrogenase, respectively. The purified glycolytic enzymes specifically bound the 23- and 29 kDa GTP-binding proteins under both denaturing and nondenaturing conditions. The association of the GTP-binding proteins with these polypeptides was resistant to detergents such as 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonic acid (CHAPS), Triton X-100, and Tween. A 23-kDa GTP-binding protein purified from chromaffin cells bound to a 157-kDa polypeptide in triads and chromaffin cell membranes. The 157-kDa polypeptide was a minor component in these membranes and not related to the subunits of the dihydropyridine receptor. In view of the proposed function of low molecular weight GTP-binding proteins in processes such as membrane communication and secretion coupling, the association of these proteins with transverse tubules and triads in skeletal muscle is discussed in terms of a role in signal transmission. PMID- 1910048 TI - The odontoid process in Morquio-Brailsford's disease. The effects of occipitocervical fusion. AB - High definition computed cervical myelograms have been made in flexion and extension in 13 patients with Morquio-Brailsford's disease. We observed that: 1) odontoid dysplasia was present in every case, with a hypoplastic dens and a detached distal portion which was not always ossified; 2) atlanto-axial instability was mild, and anterior atlanto-axial subluxation was absent in most cases; 3) severe spinal cord compression, when present, was due to anterior extradural soft-tissue thickening; 4) this compression was not relieved by flexing or extending the neck and was manifested early in life; 5) posterior occipitocervical fusion resulted in disappearance of the soft-tissue thickening and normalisation of subsequent development of the dens. We conclude that the severity of neurological involvement at the craniovertebral junction was determined by soft-tissue changes, not by the type of odontoid dysplasia nor by subluxation. Posterior occipitocervical fusion proved to be an effective treatment. PMID- 1910049 TI - A heterotrimeric G protein, G alpha i-3, on Golgi membranes regulates the secretion of a heparan sulfate proteoglycan in LLC-PK1 epithelial cells. AB - A heterotrimeric G alpha i subunit, alpha i-3, is localized on Golgi membranes in LLC-PK1 and NRK epithelial cells where it colocalizes with mannosidase II by immunofluorescence. The alpha i-3 was found to be localized on the cytoplasmic face of Golgi cisternae and it was distributed across the whole Golgi stack. The alpha i-3 subunit is found on isolated rat liver Golgi membranes by Western blotting and G alpha i-3 on the Golgi apparatus is ADP ribosylated by pertussis toxin. LLC-PK1 cells were stably transfected with G alpha i-3 on an MT-1, inducible promoter in order to overexpress alpha i-3 on Golgi membranes. The intracellular processing and constitutive secretion of the basement membrane heparan sulfate proteoglycan (HSPG) was measured in LLC-PK1 cells. Overexpression of alpha i-3 on Golgi membranes in transfected cells retarded the secretion of HSPG and accumulated precursors in the medial-trans-Golgi. This effect was reversed by treatment of cells with pertussis toxin which results in ADP ribosylation and functional uncoupling of G alpha i-3 on Golgi membranes. These results provide evidence for a novel role for the pertussis toxin sensitive G alpha i-3 protein in Golgi trafficking of a constitutively secreted protein in epithelial cells. PMID- 1910050 TI - Apical and basolateral transferrin receptors in polarized BeWo cells recycle through separate endosomes. AB - Contrary to most other epithelia, trophoblasts in the human placenta, which form the physical barrier between the fetal and the maternal blood circulation, express high numbers of transferrin receptors on their apical cell surface. This study describes the establishment of a polarized trophoblast-like cell line BeWo, which exhibit a high expression of transferrin receptors on the apex of the cells. Cultured on permeable filter supports, BeWo cells formed a polarized monolayer with microvilli on their apical cell surface. Across the monolayer a transepithelial resistance developed of approximately 600 omega.cm2 within 4 d. Depletion of Ca2+ from the medium decreased the resistance to background levels, showing its dependence on the integrity of tight junctions. Within the same period of time the secretion of proteins became polarized. In addition, the compositions of integral membrane proteins at the apical and basolateral plasma membrane domains were distinct as determined by domain-selective iodination. Similar to placental trophoblasts, binding of 125I-labeled transferrin to BeWo monolayers revealed that the transferrin receptor was expressed at both plasma membrane domains. Apical and basolateral transferrin receptors were found in a 1:2 surface ratio and exhibited identical dissociation constants and molecular weights. After uptake, transferrin recycled predominantly to the domain of administration, indicating separate recycling pathways from the apical and basolateral domain. This was confirmed by using diaminobenzidine cytochemistry, a technique by which colocalization of endocytosed 125I-labeled and HRP-conjugated transferrin can be monitored. No mixing of the two types of ligands was observed, when both ligands were simultaneously internalized for 10 or 60 min from opposite domains, demonstrating that BeWo cells possess separate populations of apical and basolateral early endosomes. In conclusion, the trophoblast-like BeWo cell line can serve as a unique model to compare the apical and basolateral endocytic pathways of a single ligand, transferrin, in polarized epithelial cells. PMID- 1910051 TI - Mitotic cytosol inhibits invagination of coated pits in broken mitotic cells. AB - Receptor-mediated endocytosis is inhibited during mitosis in mammalian cells and earlier work on A431 cells suggested that one of the sites inhibited was the invagination of coated pits (Pypaert, M., J. M. Lucocq, and G. Warren. 1987. Eur. J. Cell Biol. 45: 23-29). To explore this inhibition further, we have reproduced it in broken HeLa cells. Mitotic or interphase cells were broken by freeze thawing in liquid nitrogen and warmed in the presence of mitotic or interphase cytosol. Using a morphological assay, we found invagination to be inhibited only when mitotic cells were incubated in mitotic cytosol. This inhibition was reversed by diluting the cytosol during the incubation. Reversal was sensitive to okadaic acid, a potent phosphatase inhibitor, showing that phosphorylation was involved in the inhibition of invagination. This was confirmed using purified cdc2 kinase which alone could partially substitute for mitotic cytosol. PMID- 1910052 TI - Pharmacokinetics of ritanserin in patients undergoing hemodialysis. AB - The pharmacokinetics of ritanserin were studied in five patients with chronic renal insufficiency and who were undergoing periodic hemodialysis. Immediately after breakfast, a single 10-mg ritanserin tablet was administered to each patient on a day that they did not undergo dialysis. Plasma ritanserin levels were measured by a specific high-performance liquid chromatographic assay sensitive to 2 ng/mL plasma. After the oral 10-mg dose, the average time to reach the peak plasma concentration, Tmax, was 4.4 +/- 2.2 hours in these uremic patients, with a range of 2 to 8 hours. The average peak plasma concentration was 73.6 +/- 26.9 ng/mL (range: 54.6-120.0 ng/mL). Compared with a previous study in healthy volunteers, the uremic patients had a slower absorption profile, with a 39% reduction in peak plasma concentration and mean delay of 2.5 hours in Tmax. The mean area under the plasma concentration-time curve for ritanserin (2031 +/- 636 ng.hr/mL) was 47% lower compared with that in healthy volunteers (3867 +/- 1413 ng.hr/mL). The observed delayed and lower ritanserin absorption in these uremic patients may be caused by the chronic use of antacids such as aluminum hydroxide and calcium carbonate in all patients and/or by concurrent pathologic changes in the gastrointestinal mucosa of these patients. The regular hemodialysis sessions every 2-3 days did not affect the elimination rate of ritanserin, as the terminal half-life in these patients (39 +/- 23 hr) is similar to that in healthy volunteers (41 +/- 14 hr). PMID- 1910054 TI - Identification of a retinal protein in Drosophila with antibody to the alpha subunit of bovine brain G(o) protein. AB - An antibody directed against the alpha(o) subunit of bovine brain G(o) (R4) was used to identify a Drosophila retinal protein which may be the analogue of vertebrate transducin. The immunoreactivity appears predominantly in the retinal and occellar rhabdomeres. On a Western blot, the antibody recognizes a 41 kDa protein that is present in the heads of yellow white flies, but not in the heads of eyeless mutant flies, eyes absent. This protein is not recognized by an antibody raised against Drosophila alpha(o). Antibody R4 intensely stains rhabdomeres and, to a lesser extent, the neuropil of the central nervous system in tissue sections of adult flies. Antibody to Drosophila alpha(o) stains the neuropil of the central nervous system, but does not stain rhabdomeres. In developing flies, faint immunoreactivity appears in the retinal rhabdomeres at about 70% of the time through pupal development and increases to its apparent adult maximal level about 1 day after eclosion. Tissue sections from a phototransduction mutant, norp A, have retinal immunoreactivity at normal levels up to about 1 week after eclosion, but by 2 weeks, immunoreactivity has largely disappeared. This disappearance parallels the degeneration of the retina in norp A mutants. In Drosophila and other invertebrates, light activates a phospholipase C in the retina. The identification of a protein in Drosophila rhabdomeres with an antibody raised against a mammalian G protein alpha subunit thought to be involved in phospholipase C activation suggests that there may be common structural features between the putative Drosophila transducin and alpha(o). The identification of regions common to mammalian alpha(o) and Drosophila transducin may then provide clues to the structural requirements for PLC activation. PMID- 1910053 TI - Misoprostol does not protect articular cartilage from salicylate-induced suppression of proteoglycan synthesis. PMID- 1910055 TI - Primary anetoderma associated with a wide spectrum of autoimmune abnormalities. AB - Although the underlying pathologic mechanisms of primary anetoderma have not yet been identified, data suggest the participation of an immunologic mechanism in some cases. In a woman with clinical and histopathologic features of primary anetoderma (Jadassohn-Pellizzari type) of 30 years' duration, laboratory investigation disclosed positive antinuclear factor, hypocomplementemia, hypergammaglobulinemia, granular deposits of immunoreactants along the dermoepidermal junction, and fibrillar deposits in the papillary dermis. In addition, she was found to have autoimmune hemolysis and circulating lupus anticoagulant associated with recurrent deep-vein thrombosis and a history of Graves' disease (starting 5 years after onset of primary anetoderma). To our knowledge, none of the latter three autoimmune conditions has been previously associated with primary anetoderma. PMID- 1910056 TI - Specificity, inhibitory studies, and oligosaccharide formation by beta galactosidase from psychrotrophic Bacillus subtilis KL88. AB - beta-Galactosidase from psychotrophic Bacillus subtilis KL88 was specific to the beta-D-glycosidic linkage normally present in lactose. The enzyme was completely inhibited by transition metal ions (Cu2+, Fe3+, Fe2+, Zn2+) and partially inhibited by high concentrations of glucose and galactose as well as Ca2+. It was activated by most of the alkaline earth metal ions (NA+, K+, Li+). Oligosaccharides were formed at the different levels of lactose concentrations reaching more than 20% for high lactose concentration (20%). Three types of oligosaccharides were formed in significant concentrations detected by HPLC analysis. PMID- 1910057 TI - Performance and fecal flora of calves fed a Bacillus subtilis concentrate. AB - Eighty-four Holstein calves were assigned at 2 d of age to one of three treatments: 1) control with no additives; 2) 10 g of a mixed microbial concentrate containing Lactobacillus acidophilus, Lactobacillus lactis, and Bacillus subtilis; or 3) 10 g of a B. subtilis concentrate. The microbial concentrates were mixed with milk replacer during the a.m. feeding. The milk replacer was offered twice daily at 5% BW per feeding; the reconstituted replacer contained 12.5% DM. Volume of replacer fed was based on initial weight of calf and held constant until weaning. Water and starter ration were offered for ad libitum intake throughout the trial. Calves were weaned abruptly at 30 d of age and received only water and starter from d 31 to 44. General health and performance of all calves were good. Although differences in weight gain and feed efficiency were not significant, the B. subtilis concentrate tended to have a positive effect on feed efficiency during wk 1 to 4 and on immediate postweaning gain. A higher fecal bacilli count at 6 wk in calves fed the microbial concentrates may be related to their tendency for improved gain during d 31 to 44, the immediate postweaning period. PMID- 1910058 TI - Nitrogen metabolism of lactating ewes fed rumen-protected methionine and lysine. AB - Twenty multiparous, crossbred, black-faced ewes and their newborn twin lambs were assigned to one of four dietary treatments in a 2 x 2 factorial experiment to examine the effects of increased supply of CP or a mixture of encapsulated methionine and lysine or both on the performance of ewes and their nursing twin lambs. Ewes were fed ad libitum amounts of either a 10.2% low CP diet or a 16.2% moderate CP diet with or without additional encapsulated amino acids. Nitrogen metabolism trials were conducted simultaneously on both ewes and lambs at wk 2, 4, and 8 of lactation. Analyses were conducted for blood urea N, plasma 3 hydroxybutyrate, lactate, NEFA, insulin, and amino acids (plasma, feed, and milk). Ewe DMI, BW, BW gain, and milk yield were not changed by dietary treatments. Balance of N and N digested were increased by moderate CP treatment. The portion of retained N used for milk synthesis was increased by low CP treatment. Methionine and total branched-chain amino acids were increased by encapsulated amino acids and by protein treatment. Gains in BW and N balance were increased in lambs nursing ewes fed protected amino acids. Increased growth of nursing lambs would be an important beneficial effect of supplementing diets of ewes with encapsulated methionine and lysine. PMID- 1910059 TI - Disinfection of human teeth for educational purposes. PMID- 1910060 TI - Effects of antiarrhythmic drugs on canine atrial flutter due to reentry: role of prolongation of refractory period and depression of conduction to excitable gap. AB - Antiarrhythmic drugs prolong the effective refractory period and depress conduction. To determine the exact role played by these two electrophysiologic effects in the termination of reentry, the effects of disopyramide, flecainide, propafenone and E-4031, a new class III drug, were examined in a canine model of atrial flutter (cycle length 120 +/- 4 to 131 +/- 3 ms) caused by reentry. Atrial flutter was induced in 32 anesthetized open chest dogs after placement of an intercaval crush. The excitable gap ranged from 9 +/- 2% to 11 +/- 4% of the basic flutter cycle length. The effective refractory period in the reentrant circuit during atrial flutter was estimated by subtracting the excitable gap from the basic flutter cycle length. Prolongation of flutter cycle length by the test drugs was proportional to the interatrial conduction time (r = 0.87, p less than 0.001). Atrial flutter was terminated by each test drug in all dogs except for flecainide and propafenone in one dog each. E-4031 prolonged the refractory period during atrial flutter to 129 +/- 6 ms, which did not differ significantly from the flutter cycle length immediately before termination (134 +/- 4 ms). The refractory period during atrial flutter after injection of the other drugs was shorter than the flutter cycle length before termination of atrial flutter (for example, flecainide 126 +/- 5 vs. 179 +/- 11 ms, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1910061 TI - Enteral alimentation: administration and complications. AB - Tube feeding is commonly used for providing essential calories and nutrients to the patient otherwise unable to eat. In the last two decades there has been significant expansion in the number and quality of enteral formulas. In this review, we evaluate the indications for each major class of formula, and survey complications associated with formulas and devices that deliver formula. Recommendations for future research are listed. PMID- 1910062 TI - Intravenous vitamins for very-low-birth-weight infants. AB - Term infants and children appear to adapt to large variations in vitamin intakes. This is supported by the finding of similar blood levels of vitamins despite several-fold differences in intake on a body weight basis. By contrast, the finding of marked elevation of some vitamins and low levels of others seen in very-low-birth-weight (VLBW) infants (less than 1500 g) suggest that this group has less adaptive capacity to high- or low-dose intakes. This indicates that their vitamin intakes need to be more closely aligned with actual needs. This paper reviews previously published data on vitamins A, E, B2, and B6 from VLBW infants receiving total parenteral nutrition (TPN). Vitamin A. VLBW infants are relatively deficient in retinol (R) at birth. During TPN large losses of R onto the delivery sets result in a further decline in stores of R as reflected in a progressive decline in plasma R during TPN. Because of the reported lower incidence of bronchopulmonary dysplasia associated with intramuscular vitamin A treatment, alternative methods of vitamin A delivery during TPN have been suggested. First, the vitamins were mixed with Intralipid (IL) and, second, retinyl palmitate (RP) rather than R was used. There was little in vitro loss of R when mixed with IL, and in vivo treatment resulted in higher blood levels after 1 month of retinol administration in IL than seen previously (21.4 +/- 4.2 vs 14.1 +/- 3.7 micrograms/dl).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1910063 TI - The prognostic inflammatory and nutritional index in traumatized patients receiving enteral nutrition support. AB - The prognostic inflammatory and nutritional index (PINI) is a clinical assessment tool which aggregates serum C-reactive protein (CRP), alpha 1-acid glycoprotein (AAG), prealbumin (PA), and albumin (ALB) concentrations into a single score. This study was conducted to characterize the index and its determinants over time in 15 critically ill trauma patients receiving enteral nutritional support (ENS). Patients received 1.4 g of protein/kg/day and 32 kcal/kg/day for at least 7 days using a nutritionally complete formula supplemented with whey protein. The PINI was calculated at baseline and on days 4, 7, 10, 14, 21, and 28. The PINI decreased significantly from baseline (186 +/- 202) to day 4 (116 +/- 86) and reached a nadir at day 14 (27 +/- 40). Serum CRP concentrations decreased significantly during the study period, while PA and ALB concentrations increased significantly. There was no change in the AAG concentration. Nitrogen balance increased significantly during the study period. The PINI was positively correlated with CRP concentration (r = 0.72, p = 0.0001) and negatively correlated with PA concentration (r = 0.56, p = 0.0004 and nitrogen balance (r = 0.51, p = 0.0018). The PINI decreased significantly during ENS of critically ill trauma patients, influenced primarily by a decrease in CRP concentration. Further studies are needed to characterize the PINI's performance as a prognostic tool. PMID- 1910064 TI - Relative contributions of dietary sodium sources. AB - Information on the relative contributions of all dietary sodium (Na) sources is needed to assess the potential efficacy of manipulating the component parts in efforts to implement current recommendations to reduce Na intake in the population. The present study quantified the contributions of inherently food borne, processing-added, table, cooking, and water sources in 62 adults who were regular users of discretionary salt to allow such an assessment. Seven-day dietary records, potable water collections, and preweighted salt shakers were used to estimate Na intake. Na added during processing contributed 77% of total intake, 11.6% was derived from Na inherent to food, and water was a trivial source. The observed table (6.2%) and cooking (5.1%) values may overestimate the contribution of these sources in the general population due to sample characteristics, yet they were still markedly lower than previously reported values. These findings, coupled with similar observations from other studies, indicate that reduction of discretionary salt will contribute little to moderation of total Na intake in the population. PMID- 1910065 TI - Microbial conversion of fungicide vinclozolin. AB - An ecological safety study of using vinclozolin in field and laboratory experiments showed that the effect of the preparation led to a decrease in the abundance of actinomycetes and mycelial fungi and an enhancement of nitrification. The residual amounts of vinclozolin in soil after 12 months were 6 12% of the dose introduced. The persistent chlorinated derivatives of the toxicant were found. Microbial strains pertaining to the genera Pseudomonas and Bacillus were isolated that utilized vinclozolin as the sole source of carbon and energy. PMID- 1910068 TI - On the cost and value of second surgical opinion programs: comment and response. PMID- 1910066 TI - Has PPS increased Medicare expenditures on physicians? AB - We use data from 1983 and 1985 on the volume of Medicare physician services to analyze whether Medicare's Prospective Payment System (PPS), which resulted in a significant decline in hospital spending, led to a partially offsetting increase in real expenditures for physician services. We also analyze the effect of increases in assignment rates, increasing incomes of the elderly, and other factors on real expenditures during this period. Our main conclusion is that PPS has at most a small positive effect on real physician expenditures. Because people spent less time in the hospital, Medicare physician spending declined; but because of incentives to shift radiology and other services out of the hospital, some of this decline was offset. We also conclude that the sharp increase in Medicare assignment rates over this period, along with the rising incomes of the elderly during this period, contributed to the observed growth. PMID- 1910067 TI - How do uncompensated care pools affect the level and type of care? Results from New York State. AB - Uncompensated care pools have been used by several states in their attempt to aid hospitals and increase the volume of care provided to patients without health insurance. We examined the uncompensated care pool used in New York State between 1983 and 1987. Our primary interest was to estimate the impact of the pools on the level and type of care provided to uninsured patients. Our results indicate that hospitals responded to the pools by increasing the volume of care provided to uninsured patients. Without the pools, over 30,000 fewer adjusted hospital admissions would have been provided to the uninsured in a typical year. Many of these newly purchased admissions were for "nondiscretionary" medical care, suggesting that beneficial care to the indigent was rationed prior to the introduction of the uncompensated care pools. PMID- 1910069 TI - Risk factors for Crimean-Congo hemorrhagic fever in rural northern Senegal. AB - The extent of infection among 722 residents of an enzootic focus of Crimean-Congo hemorrhagic fever (CCHF) virus in rural northern Senegal and putative modes of transmission were studied by a cross-sectional seroprevalence survey done from February through May 1989. Anti-CCHF virus IgG was found in 13.1% of 283 persons who completed a standard questionnaire and provided blood samples. Seropositivity rates were similar between sexes and increased significantly with age among nomadic persons. Behavior patterns providing exposure to multifactorial risk factors were gender-based. Male risk factors, primarily associated with herding activities, included sleeping outside during seasonal migrations (also a risk factor for nomadic women), bite by a tick (adult male Hyalomma truncatum), tick bite during the cool dry season, and contact with sick animals. Human infection of CCHF occurred more frequently or with less mortality in the region studied than has been found elsewhere in Africa; however, the rate of seroconversion associated illness is undetermined. Hyalomma ticks appear to be the primary transmission mode. PMID- 1910070 TI - Safety, pharmacokinetics, and functional activity of human anti-Pseudomonas aeruginosa monoclonal antibodies in septic and nonseptic patients. AB - A mixture of five IgM human monoclonal antibodies (MAbs) against lipopolysaccharide antigens of Pseudomonas aeruginosa, plus a human IgG1 MAb against exotoxin A, were studied in 12 noninfected patients and 8 patients with P. aeruginosa bacteremia or pneumonia (or both). The preparation was well tolerated over a dose range of 0.3-1.2 ml/kg (0.75-3.0 mg/kg IgM protein). After a single infusion of 1.2 ml/kg (3.0 mg/kg IgM protein), serum antibody titers were boosted into therapeutic range, with serum half-lives ranging from 34 to 99 h. Also, opsonophagocytic activity in serum rose more than 1 log10 for all but one antibody. In no patient was an immunologic response against the MAb preparation detected. PMID- 1910071 TI - Low prevalence of sexual transmission of hepatitis C virus in sex partners of seropositive intravenous drug users. PMID- 1910072 TI - Absence of IgG or IgM antibody response to Mycobacterium tuberculosis 30,000-Da antigen after primary tuberculous infection. PMID- 1910074 TI - Ionized calcium in blood: studies on patients with pulmonary disease. AB - A new automatic ionized calcium analyser ICA 2 (Radiometer, Copenhagen, Denmark) was used for studies of ionized calcium (cCa2+) in the arterial blood of patients with a compensated respiratory acidosis due to chronic lung disease. The data for 16 patients showed an unexpectedly high level of variation in cCa2+ (range, 1.01 1.25 mmol l-1) despite the fact that there was only a small degree of variability in pH (range, 7.38-7.51). cCa2+ was not correlated with pH as has been observed in acute respiratory disturbances. A highly significant negative correlation was found between cCa2+ and base excess (BE) (r = -0.81, P less than 0.0001), and between cCa2+ and carbon dioxide tension (PCO2) (r = 0.71, P less than 0.002). These correlations differed from those reported previously in acute respiratory disturbances. CCa2+ showed a significant positive correlation with oxygen tension (PO2) (r = 0.71, P less than 0.002). It is concluded that cCa2+ in arterial blood from patients with chronic lung disease is correlated with acid-base and gas quantities in an entirely different manner to that observed in acute acid-base disturbances in normal adults. PMID- 1910073 TI - [A case of successful surgical repair for congenital corrected transposition of the great arteries associated with Ebstein's malformation and diverticulum of atrialized ventricle]. AB - Congenital corrected transposition of the great arteries (C-TGA) is frequently associated with VSD and PS. Systemic atrioventricular valve regurgitation is also sometimes present in patients with C-TGA. It is though that left-sided A-V valve regurgitation is caused by the deformities of the tricuspid valve (TV) or intolerance of TV and the right ventricle (RV) against systemic pressure load. We had a patient with C-TGA associated with Ebstein's malformation. The patient suffered from congestive heart failure due to left-sided A-V valve regurgitation. In this case, the septal and posterior leaflets were displaced below the atrioventricular annulus. The edges of all valves were thickened and partially calcified. Focal agenesis was found in the septal leaflet. There was a distinct atrialized ventricle which had a thin wall and no trabeculae. It shaped like a diverticulum of 3 cm in depth toward the diaphragm. Preoperative cardiac catheterization showed that the functional RV had an adequate size (RVEDVI 162% of normal) and ejection fraction was 53%. Left-sided valve replacement was performed using SJM 31M with preservation of TV. Left-sided atrioventricular annulus was so deformed due to the diverticulum that the prosthetic valve was sutured at the ventricular wall below the atrioventricular annulus to which TV had attached. Good clinical result was obtained after surgical treatment. PMID- 1910075 TI - Ca(2+)-independent, Ca(2+)-dependent, and carbachol-mediated arachidonic acid release from rat brain cortex membrane. AB - Synaptoneurosomes obtained from the cortex of rat brain prelabeled with [14C]arachidonic acid [( 14C]AA) were used as a source of substrate and enzyme in studies on the regulation of AA release. A significant amount of AA is liberated in the presence of 2 mM EGTA, independently of Ca2+, primarily from phosphatidic acid and polyphosphoinositides (poly-PI). Quinacrine, an inhibitor of phospholipase A2 (PLA2), suppressed AA release by about 60% and neomycin, a putative inhibitor of phospholipase C (PLC), reduced AA release by about 30%. An additive effect was exhibited when both inhibitors were given together. Ca2+ activated AA release. The level of Ca2+ present in the synaptoneurosomal preparation (endogenous level) and 5 microM CaCl2 enhance AA liberation by approximately 25%, whereas 2 mM CaCl2 resulted in a 50% increase in AA release relative to EGTA. The source for Ca(2+)-dependent AA release is predominantly phosphatidylinositol (PI); however, a small pool may also be liberated from neutral lipids. Carbachol, an agonist of the cholinergic receptor, stimulated Ca(2+)-dependent AA release by about 17%. Bradykinin enhanced the effect of carbachol by about 10-15%. This agonist-mediated AA release occurs specifically from phosphoinositides (PI + poly-PI). Quinacrine almost completely suppresses calcium-and carbachol-mediated AA release. Neomycin inhibits this process by about 30% and totally suppresses the effect of bradykinin. Our results indicate that both phospholipases PLA2 and PLC with subsequent action of DAG lipase are responsible for Ca(2+)-independent AA release. Ca(2+)-dependent and carbachol mediated AA liberation occurs mainly as the result of PLA2 action. A small pool of AA is probably also released by PLC, which seems to be exclusively responsible for the effect of bradykinin. PMID- 1910076 TI - Mono-ADP-ribosylation in brain: purification and characterization of ADP ribosyltransferases affecting actin from rat brain. AB - Four ADP-ribosyltransferases that acted on non-muscle actin were purified more than 3,000-fold from rat brain extract. The molecular weights of these brain ADP ribosyltransferases were 66,000 as estimated by sodium dodecyl sulfate polyacrylamide gel electrophoresis and gel filtration on TSK gel G3000SW. The Km values for NAD were approximately 20 microM. These enzymes were not inhibited by thymidine or nicotinamide, but were inhibited by ADP and ADP-ribose. Two soluble ADP-ribosylation factors purified from rat brain had different effects on the four ADP-ribosyltransferases during the ADP-ribosylation of non-muscle actin. These ADP-ribosyltransferases modified not only actin but also the stimulatory guanine nucleotide-binding protein of adenylate cyclase, Gs, and another guanine nucleotide-binding protein in brain, Go. These findings suggest that the four brain ADP-ribosyltransferases are concerned with nerve functions in the central nervous system. PMID- 1910077 TI - Differential expression of beta amyloid protein precursor (APP) and tau mRNA in the aged human brain: individual variability and correlation between APP-751 and four-repeat tau. AB - We investigated the relationship between the differential expression of beta amyloid protein precursor (APP) and tau mRNA, and the extent of beta and tau deposition in three regions from each of the 38 aged brains obtained from consecutive autopsied cases. Remarkable variabilities were noted in the ratios of APP-770/-751/-695 and four-repeat tau among elderly individuals. There was no consistent alteration in the APP differential expression among beta plaque (-), (+), and (++(-) ) groups. Also, no differences in the four-repeat tau ratios were noted among tangle (-), (+), and (++) groups. Despite these great individual variabilities, APP-751 was found to be well-correlated with four-repeat tau. It is possible that APP-751 and four-repeat tau are increasing during aging, while APP-695 and three-repeat tau are decreasing. PMID- 1910078 TI - A study on the biological behavior of human brain tumors. Part I. Arachidonic acid metabolism and DNA content. AB - The study of proliferative characteristics and biochemical aspects seem to be of great importance in order to define brain neoplastic behavior. The purpose of this study is to verify the existence of any possible correlation between Arachidonic Acid (AA) metabolism and proliferative characteristics in 30 meningiomas and 30 neuroepithelial tumors. The most represented metabolite in neuroepithelial tumors is TxB2, while 6-Keto-PGF1 alpha is the lowest represented product. Unimodal DNA distribution was observed in 66% of neuroepithelial tumors and in 87% of meningiomas. Aneuploidy was more frequent in glioblastomas and anaplastic meningiomas as previously reported; AA overall synthesis capacity and profile were similar between unimodal and bimodal cases of neuroepithelial tumors. Total AA metabolite, as well as TxB2 and PGD2, synthesis capacity are significantly higher in cases with S-phase cell percentage greater than or equal to 3% than in cases with S-phase % less than 3%. Total production of AA metabolites via the cyclooxygenase pathway is significantly higher in meningiomas with bimodal DNA distribution than in cases with unimodal DNA content; when considering S-phase cell percentage, similarly to what observed in neuroepithelial tumors, meningiomas with S% greater than 3% shows a significantly higher overall synthesis capacity for AA. AA metabolism capacity well correlates with proliferative patterns in neuroepithelial tumors: the relationship depends preferentially on TxB2 and PGD2 synthesis capacity. In cases of meningiomas, the amount of AA metabolites seem to be related to DNA content and proliferative activity when anaplastic features are histologically demonstrated. PMID- 1910079 TI - A study on the biological behavior of human brain tumors. Part II: Steroid receptors and arachidonic acid metabolism. AB - The significance of steroid receptors (SR) in human brain tumors is presently a field of intense investigation in order to clarify some aspects of the biological behavior of these neoplasms. We studied the relationship between the presence of steroid receptors and the production of metabolites of the arachidonic acid cascade which have been reported to have a role in the biological behavior of some human tumors. We found that some metabolites of arachidonic acid are produced in different amounts in brain tumors which either did or did not express some steroid receptors. In particular the PGE2 were higher in estrogen receptors (ER) positive meningiomas than in ER negative ones and 6-keto-PGF1 alpha, the stable metabolite of prostacyclin, is significantly higher in androgen receptors (AR) negative meningiomas than in AR positive ones. In neuroepithelial tumors the glucocorticoid receptors (GR) positive cases synthesized more TxB2 and less PGE2 than the GR negative ones. Our data seem to suggest that some correlations exist between the presence of some steroid receptors and arachidonic acid metabolite production. PMID- 1910080 TI - Issues in implementing clinical research in nursing home settings. AB - Researchers at four nursing home sites experienced similar problems in the informed consent process when they attempted to access a frail, cognitively impaired population to conduct a collaborative, quasi-experimental two year clinical trials study on urinary incontinence. In addition, similar institutional barriers were experienced in these geographically distant and dissimilar nursing homes. The study involved working closely with indigenous licensed nursing and nurse aide staff to implement the independent variable, an individualized toileting prescription. Successful strategies used to overcome barriers in conducting the research will be described. PMID- 1910081 TI - Redo fundoplication in infants and children with recurrent gastroesophageal reflux. AB - The Nissen fundoplication is well established as the surgical treatment for medically refractory gastroesophageal reflux (GER) in childhood. Recurrent GER following fundoplication is a challenging problem with a reported incidence ranging from 0% to 12%. From January 1974 to January 1989, 286 children have been treated for GER with Nissen fundoplication and gastrostomy tube placement at the University of Michigan C.S. Mott Children's Hospital; 242 of these children have been followed for an average of 30 months, the remaining 44 have been lost to follow-up. Twenty-nine children (12%) have developed recurrent reflux following fundoplication. Medical management with thickened upright feelings, gastrostomy feedings, or gastrojejunostomy tube feedings has been successful for 11 children with control of reflux symptoms. Five additional children who were treated nonoperatively died of coexistant medical problems within 2 months following documentation or recurrent reflux. The remaining 13 children have required redo fundoplication for wrap disruption or herniation, and an additional six children, initially treated at other institutions, have also undergone redo fundoplications. One other child treated at this hospital required redo fundoplication for a postoperative partial gastric volvulus causing gastric outlet obstruction. Of the 20 children who have undergone a second Nissen fundoplication, 16 (80%) are doing well without recurrent GER. Four children have developed recurrent GER with wrap disruption; 1 is doing well following a third fundoplication, 2 have been managed successfully with continuous feedings via gastrojejunostomy feeding tubes, and a fourth child died of complications related to a recurrent tracheoesophageal fistula. Conservative management with gastrojejunal tube feedings should be considered in the initial management of children with recurrent GER following fundoplication.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1910082 TI - HIV antigen variability in ARC/AIDS. AB - To define the natural variability of human immunodeficiency virus p24 antigen (HIV Ag) over time in untreated HIV-infected patients, we analyzed the percentage change of serum HIV Ag in 40 antigenemic ARC/AIDS subjects receiving placebo in a 24 week clinical trial. When grouped by month of observation, no differences in HIV Ag change were seen among all five 1 month observation periods (p greater than 0.4). After all 105 monthly changes (median of 3 per subject) were pooled, the mean monthly HIV Ag change was 0% change (standard deviation: 77% increase, 44% decrease). Furthermore, HIV Ag changes did not differ among all lengths of observation (from 1 to 5 months using all possible pairwise combinations of HIV Ag levels, p greater than 0.4). CD4 T-cell changes over the whole study did not correlate with HIV Ag changes over the same period. Knowledge of this broad HIV Ag variability should be useful in calculating sample size and in choosing categorical responses unlikely to occur spontaneously in clinical trials of antiviral agents where HIV Ag changes are used as surrogate markers of efficacy. PMID- 1910083 TI - Prevalence of HIV-1 infection and symptomatology of AIDS in severely malnourished children in Dar Es Salaam, Tanzania. AB - In Dar es Salaam, Tanzania, 200 children with severe malnutrition and controls matched for age, sex, and area of residence were screened for serological evidence of infection with the human immunodeficiency virus type 1 (HIV-1) over 5 months in 1988. The prevalence of HIV-1 antibodies in the malnourished group was 25.5% (51 of 200) compared with 1.5% (three of 200) in the controls. The seroprevalence rate was equally high in malnourished children above the age of 18 months (26 of 102; 25.5%), as in those below this age (25 of 98; 25.5%). The prevalence rate was higher in children with marasmus (38.2%) as compared to children with marasmic-kwashiorkor (12.3%) or kwashiorkor (12.2%). The prevalence of clinical features known to be associated with AIDS was higher in the HIV seropositive malnourished children as compared to the seronegative children. The modified World Health Organization clinical case definition of AIDS in children was also evaluated and found to have a low sensitivity and positive predictive value (62.8 and 57.1%, respectively) but a fairly high specificity (83.9%). It is recommended to routinely rule out HIV infection in malnourished children, especially those with marasmus. PMID- 1910084 TI - Practice styles and preferences of ASCRS members--1990 survey. AB - A survey of the practice styles and preferences of 1990 ASCRS members with a U.S. zip code was performed in September 1990. Approximately 3,620 questionnaires were sent and 45% (1,625) were returned prior to the cut-off date. Three main profile questions were used to cross-analyze the results: the age of the ophthalmologist, the volume of cataract surgery per month, and the geographic location. This report also compared the data with previously published surveys of the ASCRS membership. PMID- 1910086 TI - Kinetic properties and Na+ dependence of rheogenic Na(+)-HCO3- co-transport in frog retinal pigment epithelium. AB - 1. Na(+)-HCO3- co-transport across the retinal membrane of the frog retinal pigment epithelium was studied by means of double-barrelled pH-selective microelectrodes. Transient changes in the intracellular pH were monitored in response to abrupt changes in the Na+ concentration on the retinal side of the epithelium. 2. The experiments were performed as follows. The Na(+)-HCO3- co transport was inhibited by perfusing the retinal side of the epithelium with a Na(+)-free solution. The co-transport was then stimulated by changing the perfusate from the Na(+)-free solution to a solution which contained from 5 to 110 mM-Na+. The resulting inward Na(+)-HCO3- co-transport produced an intracellular alkalinization, the initial rate of which was used to calculate the initial rate of Na(+)-HCO3- co-transport, JHCO3-. 3. The Na+ dependence of the Na(+)-HCO3- co-transport was studied at two different values of extracellular pH (7.40 and 7.10), at constant extracellular HCO3- concentration (27.5 mM) and at two different extracellular HCO3- concentrations (27.5 mM and 55 mM) at constant extracellular pH (7.40). In these experiments, the calculated values of JHCO3- followed single Michaelis-Menten kinetics with respect to the extracellular Na+ concentration. 4. The data are consistent with a model in which the co transporter has a single binding site for the Na+ ion with an apparent affinity constant (apparent Km) of 37 mM. The apparent affinity constant for Na+ was independent of the extracellular concentration of CO3(2-) in the range of 16-65 microM, and of the extracellular HCO3- concentration in the range 27.5-55 mM. 5. The NaCO3- ion-pair hypothesis, in which sodium binds to the co-transporter and is translocated across the cell membrane as the NaCO3- ion pair, was analysed. For stoichiometries 1:2 and 1:3 of the Na(+)-HCO3- co-transport, the NaCO3- ion pair hypothesis was found incompatible with the data. 6. The intracellular buffer capacity as measured by the CO2 method was 15 mM. PMID- 1910085 TI - Intestinal absorption of the intact peptide carnosine in man, and comparison with intestinal permeability to lactulose. AB - 1. Healthy humans ingested the dipeptide carnosine (L-beta-alanyl-L-histidine). Their plasma levels and urinary outputs of carnosine and beta-alanine were monitored over the following 5 h. 2. Large amounts of intact carnosine (up to 14% of the ingested dose) were recovered in the urine over the 5 h after ingestion. However, carnosine was undetectable in the plasma unless precautions were taken to inhibit blood carnosinase activity ex vivo during and after blood collection. 3. The amount of carnosine recovered in urine varied substantially between subjects. It correlated negatively with carnosinase enzymic activity in the plasma. Highest carnosinase activities were observed in those subjects who regularly underwent physical training. 4. Urinary recovery of the disaccharide lactulose also varied considerably between subjects, but was substantially lower than that of carnosine. There was no significant correlation between the recoveries of carnosine and lactulose. 5. When lactulose was ingested with a hypertonic solution, the urinary recovery of lactulose was generally increased. When carnosine was ingested with a hypertonic solution, the urinary recovery of carnosine was reduced: hence the paracellular route probably is not dominant for absorption of intact carnosine. 6. Intact carnosine must have crossed the intestine to an extent much greater than hitherto recognized. Rapid post absorptive hydrolysis is a severe obstacle to quantification of intact peptide absorption. PMID- 1910088 TI - Septic gonococcal arthritis. PMID- 1910089 TI - Design and synthesis of HIV protease inhibitors. Variations of the carboxy terminus of the HIV protease inhibitor L-682,679. AB - A series of tetrapeptide analogues of 1 (L-682,679), in which the carboxy terminus has been shortened and modified, was prepared and their inhibitory activity measured against the HIV protease in a peptide cleavage assay. Selected examples were tested as inhibitors of virus spread in cell culture. Compound 12 was a 10-fold more potent enzyme inhibitor than 1 in vitro and 30-fold more potent in inhibiting the viral spread in cells. PMID- 1910087 TI - A voltage-dependent potassium current in rabbit coronary artery smooth muscle cells. AB - 1. Voltage- and time-dependent outward currents were recorded from relaxed enzymatically isolated smooth muscle cells from the rabbit left descending coronary artery using a single pipette voltage clamp technique. The calcium activated potassium current was blocked by inclusion of EGTA in the pipette solution and CdCl2 in the extracellular bath. 2. Outward currents were elicited with depolarizing voltage steps to potentials positive to -20 mV. Long (5 s) voltage steps revealed slow inactivation of the current with a time constant of nearly 3 s at +60 mV. Potassium was identified as the predominant charge carrier by reversal potential measurements in potassium substitution experiments. 3. The results of kinetic analyses compared favourably with the Hodgkin-Huxley model for a delayed rectifier with some deviations. The sigmoid current onset was best fitted by raising the activation variable (n) to the second power. Deactivation tail currents were consistently found to be comprised of two exponential components. The kinetics of activation and deactivation were strongly voltage dependent from -80 to +60 mV. 4. Envelope of tails experiments showed that the scaled tail current amplitudes followed the kinetic behaviour of current activation. The contribution of each of the two exponential tail components was also measured in these experiments. They did not reveal kinetically separable currents, nor were they differentially altered by 4-aminopyridine (4-AP), tetraethylammonium (TEA), or elevated [K+]o. 5. The steady-state voltage dependence curves for both activation and inactivation were well fitted by a Boltzmann distribution with V1/2 = -5.60 mV and k = -8.66 mV for n infinity act and V1/2 = -24.20 mV and k = 5.16 mV for n infinity act. Super-imposition of the two curves revealed a 'window' of voltage where channels are available for activation without completely inactivating. 6. Neither of the commonly used potassium channel blockers, TEA or 4-AP, were particularly effective blockers of IK, reducing current by only 50-70% at an extracellular concentration of 10 mM. TEA block was mildly voltage-dependent and was more effective in reducing current towards the end of a 500 ms depolarization. 4-AP, on the other hand, demonstrated considerable voltage-dependence and preferentially reduced early currents. 7. Outward currents recorded from guinea-pig and human coronary artery myocytes under the same conditions as in the rabbit cell experiments displayed similar characteristics.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1910092 TI - Sister chromatid exchange evaluation as an aid to the diagnosis and exclusion of Fanconi's anaemia by induced chromosome damage analysis. AB - Evaluation of chromatid aberrations induced in culture by DNA cross linking agents provides the most reliable method currently available for the diagnosis and exclusion of Fanconi's anaemia. However, at appropriate concentrations of clastogenic agent the aberration frequency in an unaffected subject may be very low and thus it may be difficult to confirm that the treatment was effective. Data are presented to show that sister chromatid exchange analysis can be used to monitor the effectiveness of the clastogen treatment and thereby increase the reliability and efficiency of the assay. PMID- 1910090 TI - Dual-action cephalosporins: cephalosporin 3'-quinolone carbamates. AB - A series of cephalosporins has been prepared in which the 3'-position was linked to the nitrogen of the antibacterial quinolone ciprofloxacin through a carbamate function. Like the ester-linked and quaternary-linked dual-action cephalosporins reported earlier, these carbamate-linked compounds exhibited a broad antibacterial spectrum derived from both cephalosporin-like and quinolone-like activities, suggesting a dual mode of action. Studies to elucidate details of the mechanism of action have been inconclusive. Ciprofloxacin liberated as a consequence of bacterial enzyme-mediated reactions may contribute to the second mode of action, although some evidence indicates that the intact carbamate-linked bifunctional molecules may possess intrinsically both beta-lactam and quinolone activities. PMID- 1910091 TI - Interphenylene 7-oxabicyclo[2.2.1]heptane thromboxane A2 antagonists. Semicarbazone omega-chains. AB - A series of chiral interphenylene 7-oxabicyclo[2.2.1]heptane semicarbazones 19-26 were prepared and evaluated for their in vitro thromboxane (TxA2) antagonistic activity and in vivo duration of action. The potency of 19-26 was found to highly dependent on the substitution pattern of the interphenylene ring and decreased in the order ortho greater than meta much greater than para. SQ 35,091 (25), [1S-(1 alpha,2 alpha,3 alpha,4 alpha)]-2-[[3-[[[(phenylamino) carbonyl]hydrazono]methyl] 7-oxabicyclo[2.2.1]hept-2-yl]methyl] benzenepropanoic acid, was identified as a potent and long-acting TxA2 antagonist. In human platelet rich plasma SQ 35,091 inhibited arachidonic acid (800 microM) and U-46,619 (10 microM) induced aggregation with I50 values of 3 and 12 nM, respectively. In contrast, no inhibition of ADP (20 microM) induced aggregation was observed at greater than 1000 microM. Receptor binding studies with [3H]-SQ 29,548 showed SQ 35,091 was a competitive antagonist with a Kd value of 1.0 +/- 0.1 nM in human platelet membranes. In vivo SQ 35,091 (0.2 mg/kg po) showed extended protection (T50 = 16 h) from U-46,619 (2 mg/kg iv) induced death in mice. These compounds have for the first time demonstrated that a metabolically stable interphenylene alpha sidechain can be introduced into a prostanoid-like series of TxA2 antagonists with the maintainance of potent antagonistic activity. PMID- 1910093 TI - Tyrosinase positive albinism with familial 46,XY,t(2;4) (q31.2;q31.22) balanced translocation. AB - A subject with clinical and biochemical tyrosinase positive oculocutaneous albinism (OCA) also had a balanced translocation, 46,XY,t(2;4)(q31.2;q31.22). This observation provides evidence for a possible gene locus in the q31 region of chromosome 2 or 4. PMID- 1910094 TI - Congenital intestinal pseudo-obstruction associated with a giant platelet disorder. PMID- 1910096 TI - Anaerobic work and power output during cycle ergometer exercise: effects of bicarbonate loading. AB - Eight trained male cyclists who competed regularly in track races, were studied under control, alkalotic (NaHCO3) and placebo (CaCO3) conditions in a laboratory setting to study the effect of orally induced metabolic alkalosis on 60 s anaerobic work and power output on a bicycle ergometer. Basal, pre- and post exercise blood samples in the three conditions were analysed for pH, pCO2, pO2, bicarbonate, base excess and lactate. All blood gas measurements were within normal limits at basal levels. There were significant differences in the amount of work produced, and in the maximal power output produced by the cyclists in the experimental condition when compared to the control and placebo conditions (P less than 0.01). The post-exercise pH decreased in all three conditions (P less than 0.05) and post-exercise pCO2 increased significantly in the alkalosis trial (P less than 0.01). In the alkalotic condition, the pre-exercise base excess and HCO3- levels were both higher (P less than 0.05) than the basal levels, suggesting that the bicarbonate ingestion had a significant increase in the buffering ability of the blood. Post-exercise lactate levels were significantly higher (P less than 0.05) after the alkalotic trial when compared to the other two conditions, immediately post-exercise and for the next 3 min. Post-exercise lactate levels were higher than basal or pre-exercise levels (P less than 0.001). This was true immediately post-exercise and for the next 5 min. The results of this study suggest that NaHCO3 is an effective ergogenic aid when used for typically anaerobic exercise as used in this experiment. We feel that this ergogenic property is probably due to the accelerated efflux of H+ ions from the muscle tissue due to increased extracellular bicarbonate buffering. PMID- 1910097 TI - Relationship between blood lactate and excess CO2 in elite cyclists. AB - This study examined the relationship between expired non-metabolic CO2 (exCO2) and the accumulation of blood lactate. Particular emphasis was placed on the ventilatory (exCO2 and VE/VO2) and lactate threshold relationship. A total of 21 elite cyclists (15 males, 6 females) performed a progressive intensity bicycle ergometer test during which ventilatory parameters were monitored on-line at 15-s intervals, and blood lactate sampling occurred at each minute. Transition threshold values were determined for each of the three indices: excess CO2 (TexCO2), VE/VO2 (Tvent) and blood lactate (Tlac). The three threshold values (TexCO2, Tvent, Tlac) all correlated significantly (P less than 0.001) when each was expressed as an absolute VO2 (l min-1). A significant ANOVA (F = 8.41, P less than 0.001) and post-hoc correlated t-tests demonstrated significant differences between the TexCO2 and Tlac (P less than 0.001) and the TexCO2 and Tvent values (P less than 0.025). The Tlac occurred at an average blood lactate concentration of 3.35 mM, while the mean expired excess CO2 volume at the TexCO2 was 14.04 ml kg-1 min-1. Over an 11-min range across the threshold values (TexCO2 and Tlac), which were used as relative points of reference, the expired excess CO2 volume (ml kg-1 min-1) and blood lactate concentration (mM) correlated significantly (r = 0.69, P less than 0.001). Higher individual correlations over the same period of time (r = 0.82-0.96, P less than 0.001) stress the individual nature of this relationship. These results indicate a strong relationship between the three threshold values.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1910099 TI - The competitive marketplace for research funding. PMID- 1910098 TI - Treatment of murine transitional cell carcinoma with intralesional interleukin 2 and murine interferon gamma. AB - The antitumor effect of intralesionally administered recombinant interleukin-2, alone or in combination with recombinant interferon gamma was studied in murine transitional cell carcinoma, MBT2. In the initial prophylactic model treatment was started at day one at the site of tumor inoculation. Maximal and significant reduction in tumor volume occurred in groups receiving 4,000 units of recombinant interleukin 2 and 10(7) colony forming units Bacillus Calmette Guerin (p less than 0.00001 vs saline control). In the same experiment, a reduction in tumor incidence and increase in survival occurred in groups receiving 4,000 units of recombinant interleukin 2, 1,000 units of recombinant interleukin 2 plus 2,000 units of recombinant interferon gamma, as well as 10(7) colony forming units Bacillus Calmette Guerin relative to saline control (p less than 0.005). The dose response effect of recombinant interleukin 2 alone was also tested in a model of an established transitional cell carcinoma. Intralesional injection treatments were initiated after tumors were palpable. Reduction in tumor volume was observed in the group receiving 8,000 units of recombinant interleukin 2 (p = 0.01 vs saline control), but no significant advantage in survival was noted. PMID- 1910095 TI - Skeletal muscle ATP-sensitive K+ channels recorded from sarcolemmal blebs of split fibers: ATP inhibition is reduced by magnesium and ADP. AB - A new, nonenzymatically treated preparation of amphibian sarcolemmal blebs has been used to study the regulation of skeletal muscle ATP-sensitive K+ [K(ATP)] channels. When a frog skeletal muscle fiber is split in half in a Ca(2+)-free relaxing solution, large hemispherical membrane blebs appear spontaneously within minutes without need for Ca(2+)-induced contraction or enzymatic treatment. These blebs readily formed gigaseals with patch pipettes, and excised inside-out patches were found to contain a variety of K+ channels. Most prominent were K(ATP) channels similar to those found in the surface membrane of other muscle and nonmuscle cells. These channels were highly selective for K+, had a conductance of approximately 53 pS in 140 mM K+, and were blocked by internal ATP. The presence of these channels in most patches implies that split-fiber blebs are made up, at least in large part, of sarcolemmal membrane. In this preparation, K(ATP) channels could be rapidly and reversibly blocked by glibenclamide (0.1-10 microM) in a dose-dependent manner. These channels were sensitive to ATP in the micromolar range in the absence of Mg. This sensitivity was noticeably reduced in the presence of millimolar Mg, most likely because of the ability of Mg2+ ions to bind ATP. Our data therefore suggest that free ATP is a much more potent inhibitor of these channels than MgATP. Channel sensitivity to ATP was significantly reduced by ADP in a manner consistent with a competition between ADP, a weak inhibitor, and ATP, a strong inhibitor, for the same inhibitory binding sites. These observations suggest that the mechanisms of nucleotide regulation of skeletal muscle and pancreatic K(ATP) channels are more analogous than previously thought. PMID- 1910100 TI - Effects of immediate postoperative enteral nutrition on body composition, muscle function, and wound healing. AB - Thirty-two patients undergoing bowel resection were randomized to receive either immediate postoperative nasojejunal feeding with full strength Osmolite solution for 56 hours (n = 16) or routine postoperative hypocaloric fluids and gradual reintroduction of diet (n = 16). Body composition changes were measured at 14 days after operation with in vivo neutron activation analysis, the wound healing response by subcutaneous implantation of Gortex tubes, and muscle function by grip strength, maximum ventilatory volume, and stimulation of the ulnar nerve at the wrist. Postoperative fatigue up to 3 months after operation was assessed using a 10-point analogue. Successful immediate enteral nutrition was established in 12 of the 16 patients. Enterally fed patients had a mean daily caloric intake of 1179 +/- 388 kcal/d (mean +/- SD) over the first 4 postoperative days compared with 382 +/- 71 kcal/d for the controls (p less than 0.0001). The amount of hydroxyproline accumulating in the Gortex tubes was also significantly greater (2.5 +/- 1.1 nmol/g tube vs 1.5 +/- 0.8 nmol/g tube; p less than 0.02). However, the amount and composition of the weight lost was not significantly different. Muscle function was not preserved, and postoperative fatigue occurred to an equal extent in both groups. Complications were similar in both groups, except for a preponderance of bowel obstructions in the controls. The time to passage of first flatus and first bowel motion, although shorter in the fed group, did not reach significance (p = 0.07). We conclude that immediate enteral nutrition is feasible and results in an improved wound healing response.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1910101 TI - Four years of North American registry home parenteral nutrition outcome data and their implications for patient management. AB - The OASIS Registry started annual collection of longitudinal data on patients on home parenteral nutrition (HPN) in 1984. This report describes outcome profiles on 1594 HPN patients in seven disease categories. Analysis showed clinical outcome was principally a reflection of the underlying diagnosis. Patients with Crohn's disease, ischemic bowel disease, motility disorders, radiation enteritis, and congenital bowel dysfunction all had a fairly long-term clinical outcome, whereas those with active cancer and acquired immunodeficiency syndrome (AIDS) had a short-term outcome. The long-term group had a 3-year survival rate of 65 to 80%, they averaged 2.6 complications requiring hospitalization per year, and 49% experienced complete rehabilitation. The short-term group had a mean survival of 6 months; they averaged 4.6 complications per year and about 15% experienced complete rehabilitation. The registry data also indicated HPN was used for 19,700 patients in 1987 with therapy growth averaging about 8% per year. This growth was chiefly from new cancer patients. The number of new patients with long-term disorders in whom HPN was initiated appeared rather constant. We conclude that these clinical outcome assessments justify HPN for long-term patients, but the utility and appropriateness of HPN for the cancer and AIDS patients remains uncertain and requires further study. Medical, social, and fiscal aspects of HPN management in long-term and short-term patients appear to involve quite separate considerations. PMID- 1910102 TI - A prospective study of outcome from protein-energy malnutrition in nursing home residents. AB - To study recovery from protein-energy malnutrition in patients newly admitted to a chronic care facility, biochemical and anthropomorphic malnutrition indicators were measured prospectively over a 2-month period. Subjects were observed for a mean of 76 +/- 18 days after admission. Factors which might affect nutritional status including method of feeding, energy prescribed, use of supplemental feedings, assistance in eating, and amount of diet consumed were recorded. Confounding variables including illness, mental status, functional status, or prescription drugs were evaluated for their impact. On the basis of an empiric nutrition score, 54% of newly admitted residents were malnourished. Improvement in nutritional score occurred in 63% of malnourished patients remaining in the facility whereas 37% remained malnourished. Two related factors, percentage of diet consumed and degree of assistance required in eating, were important differences in the outcome of patients remaining malnourished. Interventional studies to determine whether outcome can be improved by more aggressive feeding methods or by feeding teams need to be undertaken. PMID- 1910103 TI - Prospective randomized evaluation of two regimens for converting from continuous to intermittent feedings in patients with feeding gastrostomies. AB - Forty enterally fed male patients were randomized to one of two regimens designed to determine the better means of converting them from continuous to intermittent enteral feedings. All patients received a nutritionally complete iso-osmolal 1 kcal/cc formula containing 6 g of nitrogen/L beginning on the second postgastrostomy day. Half of the patients (20) were randomized to a discontinuous regimen abruptly changing from continuous to gradually increasing intermittent feedings until reaching their nutritional goals. Intravenous fluids were given to maintain normal fluid balance. The other 20 patients were randomized to an overlapping regimen, receiving continuous feedings at a decreasing rate while intermittent feedings were progressively increased. Intravenous fluids were used during the first three stages only. There were no significant differences (p less than 0.05) in major diagnosis, type of gastrostomy, age, weight, height, admission or discharge serum albumin concentration, calculated basal energy expenditure (BEE), or nutrient goals (1.5 X BEE, 1.5 g of protein/kg per day).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1910104 TI - Effects of enteral fat emulsion on fat absorption in obstructive jaundiced rats. AB - The effects of fat emulsion given enterally on fat absorption were studied with obstructive jaundiced rats (J group) as compared with jaundice-free rats (C group). The J and C groups were subdivided into JE and CE groups using emulsified fat for the fat absorption test, and JU and CU groups using unemulsified fat. Rats in all groups were fed for 7 days with regular rat chow. After fasting for 12 hours, 14C-labeled fat emulsion was infused to the JE and CE, and 14C-labeled unemulsified fat to the JU and CU groups through a gastrostomy for the absorption test. The hourly and cumulative output of 14CO2 by respiration, absorption rate of 14C-labeled fat in the intestine, and metabolic oxidation rate of the absorbed fat were determined during an 8-hour period after the gastroenteral administration of emulsified or unemulsified fat. The peak of hourly output was seen after the first 2 hours in the CE, JE, and CU groups, following which a remarkable decline was seen in the CE and CU groups. However, a more gentle descent in the JE, and fluctuation at a low level in the JU group were observed. The cumulative output in the JE was 61% of that in the CE, while the output in the JU was 16% of that in the CU group. The absorption rate in the JE was 81% of that in the CE group, while the rate in the JU was 22% of that in the Cu group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1910105 TI - Continuous infusion of insulin in hyperglycemic low-birth weight infants receiving parenteral nutrition with and without lipid emulsion. AB - The efficiency of a continuous infusion of insulin in improving glucose tolerance was compared in two groups of very low-birth weight infants (mean +/- SEM birth weights 757 +/- 40 vs 828 +/- 80 g and gestational ages 27.6 +/- 0.7 vs. 27.2 +/- 0.5 weeks) receiving total parenteral nutrition with and without the addition of lipid emulsion to the nutrition regimen. The mean +/- SEM cumulative doses of insulin (0.87 +/- 0.1 vs 1.15 +/- 0.3 U/kg) and hours required to decrease the blood glucose level to 120 mg/dL (9.1 +/- 0.8 vs 9.5 +/- 1.0 hours) were similar. Insulin was delivered with a syringe pump used for other routine purposes in the neonatal intensive care unit. Continuous intravenous insulin infusion is an effective, inexpensive, safe method for maintaining glucose homeostasis in low birth weight infants who develop hyperglycemia as a consequence of total parenteral nutrition. PMID- 1910106 TI - Parenteral nutrition and oral intake: effect of glucose and fat infusions. AB - The effect of intravenous nutrition on voluntary oral intake was studied in healthy male volunteers. Subjects were confined to the Surgical Metabolic Unit for the 17 to 19 day study and were restricted to commercial liquid diet. Each study consisted of three consecutive phases: (1) Ringer's lactate (RL), (2) peripheral parenteral nutrition (PPN) administered for 5 or 6 days as a combination of glucose (caloric load equal to 34% resting energy expenditure, REE), fat (34% REE), and amino acids (17% REE) or a single nutrient infusion of glucose (68% REE), fat (68% REE), glucose (34% REE), or fat (34% REE), and (3) RL for the third period. When all three nutrients or glucose alone (68% REE) were given, subjects decreased daily voluntary food intake within 24 to 48 hr by an amount that closely compensated for the infused calories. Intake was reduced by only 20% to 40% of the infused calories when fat alone (68% REE) was given. There were no significant effects when the lower levels of glucose and fat were given. These data suggest the presence of a postabsorptive control of food intake in humans that is sensitive to the circulating supply of fuels. PMID- 1910107 TI - Survival in septic guinea pigs is influenced by vitamin E, but not by vitamin C in enteral diets. AB - Oxygen-free radicals are produced during sepsis, and may contribute to cell injury and dysfunction. We studied the effect of different levels of vitamins E and C in the diet fed enterally to septic guinea pigs. Sixty-four female guinea pigs were provided with gastrostomies and allowed to recover. Intraperitoneal osmotic pumps were then implanted that provided effusion of Escherichia coli and Staphylococcus aureus for the next 7 days. Three days after pump implantations, the animals were started on one of nine diets. The diets were isocaloric and isonitrogenous, and differed only in the amounts of vitamins E and C. Three levels of each vitamin were used, based on the Recommended Daily Allowance (RDA). The feedings were continued for 2 weeks, during which time mortality was observed. The amount of vitamin C had no effect on outcome, with mortality rates of 68% (15/22) in the 1 x RDA group, 73% (16/22) in the 5 x RDA group, and 65% (13/20) in the 25 x RDA group. However, vitamin E altered outcome significantly, with mortality rates of 86% (18/21) in the 1 x RDA group, 45% (10/22) in the 3 x RDA group, and 76% (16/21) in the 9 x RDA group. Mortality in the 3 x RDA group was significantly lower than that in the 1 x RDA group and in the 9 x RDA group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1910108 TI - Effects of glutamine infusion on colonic anastomotic strength in the rat. AB - Glutamine is one of the primary respiratory fuels of the colon. However, it is not included in commercial preparations of parenteral nutrients because of its short shelf life. It has been suggested that colonic atrophy induced by conventional parenteral nutrition can be reversed by the intravenous infusion of fresh solutions of glutamine. This study evaluated the hypothesis that glutamine enriched parenteral nutrition would enhance the strength of a standard colonic anastomosis in undernourished rats. After surgery, the rats were randomized to receive 6 days of postoperative support with either rat chow, conventional parenteral nutrition, or parenteral nutrition containing 1.2% glutamine. Measurement of colonic bursting tension failed to demonstrate any significant differences between the groups under study. In conclusion, the administration of 1.2% glutamine-enriched parenteral nutrition failed to influence the healing of colonic anastomoses in undernourished rats. PMID- 1910109 TI - Effect of total parenteral nutrition with xylitol on protein and energy metabolism in thermally injured rats. AB - The use of xylitol as an alternative carbohydrate calorie source in total parenteral nutrition may offer unique pharmacologic and nutritional properties in the therapy of the thermally injured. Male Sprague-Dawley rats (250 g) received a 15-second dorsal scald injury (25-30% BSA) and were parenterally fed isovolemic diets (60 ml/day) that provided 200 kcal/kg/d, 9.68 g of amino acids/kg/d, and 23.5% nonprotein calories (NPC) as fat for 3 days. The balance of NPC were provided as dextrose (Dex) or 50% xylitol:50% dextrose (Xyl/Dex). Rectus muscle and liver fractional protein synthetic rates (FSR, %/day), whole body leucine appearance (Flux), oxidation (OX), protein breakdown (PB), and synthesis (PS) were estimated using a 4-hour iv infusion of [1-14C]leucine on day 3. Mean values (+/- SE) for leucine kinetics (mumol leucine/hr/100 g), cumulative nitrogen balance (mg N) and plasma insulin concentration (Table I). (microU/mL). The partial replacement of dextrose calories with xylitol did not significantly alter whole body and tissue leucine kinetics, daily and cumulative nitrogen balance, insulin concentration, and energy expenditure (indirect calorimetry). These data indicate that xylitol may be useful as an alternative carbohydrate calorie source in parenteral nutrition to avoid possible deleterious side effects of glucose overfeeding in the critically ill but did not improve protein metabolism under the conditions of this study. PMID- 1910110 TI - Tissue uptake and oxidation of disodium sebacate in man. AB - In order to better ascertain its possible use as an alternative fuel substrate in total parenteral nutrition, sebacate (Sb) metabolism was studied in seven overnight-fasting healthy male volunteers, who received a constant iv infusion (99 mmoles over 8 hours) of disodium sebacate. Sb oxidation rate was determined using an isotopic sebacate (disodic salt of (1-10)14C-sebacic acid) infusion (100 mu Ci from the fourth to the eighth hour of the cold sebacate infusion). Blood samples were collected during and after sebacate infusion at intervals of 30 minutes and Sb serum concentrations were determined by high performance liquid chromatography. Excreted radioactivity (mu Ci/min) was measured by bubbling the expired air into an apparatus containing 3 mEq hyamine to trap CO2 from a 20-L Douglas-bag. CO2 production and O2 consumption were measured before and at 4 and 8 hours after starting the infusion. Twenty-four hour nitrogen excretion with urine was obtained. The RQ and the percent of calories derived from lipid oxidation were calculated by indirect calorimetry. The Sb serum level at the plateau phase was (mean +/- SD) 4.54 +/- 0.71 mumole/mL, the overall rate of tissue uptake was 180.89 +/- 4.50 mumole/min, and the percent oxidation was 6.14 +/- 0.44%. At the end of Sb infusion the RQ dropped to 0.839 +/- 0.043, the percent of calories due to sebacate oxidation was 1.59 +/- 0.52%, and the calories derived from lipids increased to 37.77 +/- 12.90%. These data show that a definite amount of the sebacate infused is oxidized in human tissues. PMID- 1910111 TI - Tunneled central venous catheter sepsis: risk factors in a pediatric hospital. AB - All tunnelled central venous catheters (TCVC) placed at the Alberta Children's Hospital in Calgary, Alberta, between November 1984 and July 1987, were retrospectively reviewed to study the association of catheter infection with a number of factors including age, diagnosis, catheter use, and areas caring for children. One hundred children received 130 silastic catheters placed for a total of 17,861 days. Each catheter survived a median of 100 days. Thirty-one episodes of catheter sepsis were identified (one episode for each 576 days of catheter use). Children under 2 years of age had more than two times the risk of catheter infection (p less than 0.01). Children with malabsorption had a greater risk (45.7%) than did those with infection (25.0%) or cancer (15.5%). The use of catheters for total parenteral nutrition (TPN) or for multiple purposes markedly increased the risk of catheter infection. The risk of infection of TCVC appears to be great in the young child, in particular, in those requiring TPN or multiple intravenous infusions. Use of TCVC in these children should be avoided if possible. PMID- 1910112 TI - Infusion of enteral vs parenteral nutrients using high-concentration branch-chain amino acids: effect on wound healing in the postoperative rat. AB - Starting total parenteral nutrition (TPN) the day after acute surgical stress has beneficial effects on body weight, nitrogen balance, and colonic anastomosis bursting pressure in normally nourished rats. In view of the reported favorable utilization of high-concentration branch-chain amino acids (BCAA) following severe stress, we compared enteral (TEN) to parenteral (TPN) nutrient infusions containing increased BCAA starting the day of operation. Twenty-four male Sprague Dawley rats, in two groups paired by weight under IP pentobarbital anesthesia underwent jugular vein catheter (CVP) insertion, laparotomy, gastrostomy, colon anastomosis, dorsal skin incision and SC polyvinyl alcohol sponge insertion. The rats were maintained for 6 days with continuous IV infusion in the TPN group (gastrostomy plugged) and continuous gastric infusion for the TEN group (CVP plugged). Urine and feces were collected daily. The infusions contained 1000 to 1002 Kcal, 847 to 845 nonprotein Kcal, 38 to 39 g of amino acids, 206 to 209 g of carbohydrates, and 2.8 to 2.9 g of rat per liter in the TEN and TPN, respectively, with identical ratios of dietary essential amino acids to nonessential amino acids (52/48), and 28.34% BCAA in the TPN and 33.10% BCAA in the TEN. There were 491 mg/100 mL of glutamine in the TEN and 170 mg of glutamic acid in the TPN. Amino acids were infused at 8.59 g/kg per day for TEN and 8.34 g/kg per day for TPN. The vitamins, minerals, and trace minerals were essentially the same in the TEN and TPN except for the absence of iron, iodine, selenium, and molybdenum in the TPN.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1910113 TI - Glycero- vs glucose-phosphate in parenteral nutrition of premature infants: a comparative in vitro evaluation of calcium/phosphorus compatibility. AB - In total parenteral nutrition (TPN) of premature infants, glycero- and glucose phosphate have been recommended, and clinically used, because of their considerable compatibility with calcium. However, a systematic comparative in vitro assessment of the therapeutic potential and safety of these substances has not yet been provided. We investigated the stability of TPN solutions containing calcium-gluconate and glycero- or glucose-phosphate in high concentrations. Evaluation was performed by visual inspection, absorptiometry, light microscopy, measurement of pH, and determination of calcium concentration before and after microfiltration. Even under circumstances promoting precipitation of calcium and phosphate--such as body temperature, relatively high pH, and concentrations of calcium and phosphorus exceeding those necessary to provide intrauterine accretion rates, all but one of the examined TPN admixtures remained stable. Our data suggest that the use of glycero-phosphate, and particularly glucose phosphate, together with calcium-gluconate, is an uncomplicated and safe procedure to administer simultaneously high amounts of calcium and phosphorus in TPN of premature infants. PMID- 1910114 TI - Septicemia caused by contaminated parenteral nutrition pouches: the refrigerator as an unusual cause. AB - Eleven patients in a hospital presented with septicemia caused by Enterobacter cloacae. The origin was the contamination of parenteral nutrition admixture from a resting place in the refrigerator of the parenteral mixture preparation room. PMID- 1910115 TI - Availability of insulin from TPN solutions. PMID- 1910116 TI - Comparative uses and cost for TPN in the United States, Canada, and the United Kingdom. PMID- 1910117 TI - Human serum albumin inhibits prostacyclin production by endothelial cells: the relation of the inhibitory activity to sulfhydryl groups in albumin. AB - Human serum inhibited calcium ionophore-induced production of prostacyclin by cultured bovine aortic endothelial cells. The inhibitory fraction was purified from serum by anion-exchange and Blue-Sepharose affinity chromatography. The molecular weight of the purified substance was 67k dalton as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. It was identified as human serum albumin by N-terminal amino acid sequence analysis. Human serum albumin was separated to two forms by high-performance liquid chromatography: mercaptalbumin (SH type) and nonmercaptalbumin (SS type). Both types of albumin inhibited the conversion of arachidonic acid to prostaglandin H2 in a dose-dependent manner without affecting phospholipase A2 or prostacyclin synthetase. This inhibition was more potent in mercaptalbumin than in nonmercaptalbumin. These results suggest that the conversion between mercaptalbumin and nonmercaptalbumin may play an important role in the modulation of prostacyclin synthesis by endothelial cells. PMID- 1910118 TI - [A kinetic study on serum prolactin concentration in the thyrotropin-releasing hormone test]. AB - In order to estimate the mechanism of prolactin secretion using the kinetic model, serum prolactin concentrations in normal young men were measured by an immunoradiometric assay before and after intravenous administration of 500 micrograms of thyrotropin-releasing hormone (TRH). The kinetic model was applied to evaluate the secretion rate both before and after the administration of TRH. A good correlation between the calculated values and measured values of serum concentration was observed (r = 0.995); and the adequacy of the model was confirmed. A few minutes (1.97 +/- 0.57 min) after the administration of TRH, the secretion of prolactin was stimulated, and serum prolactin concentration was maximum at 12.7 +/- 2.1 min. The total amounts of secreted prolactin was 75.4 +/- 18.4 ng/ml, which corresponded to the amount that was secreted in 4.3 hours at the normal rate. The half-life of prolactin was 40.8 +/- 13.8 min, which is in good agreement with the previously reported values. We have already reported on the kinetic study on the TSH secretion after TRH. Comparing the concentration change of prolactin and TSH, which were reported previously, it was found that the stimulated secretion started almost simultaneously, but lasted longer with respect to TSH. PMID- 1910119 TI - Effect of rapid alteration in glucose concentration and insulin on thymidine uptake in bovine retinal capillary endothelium. AB - The effect of insulin and rapid changes in glucose concentration on bovine retinal capillary endothelium (BRCE) was examined by use of tissue culture and 3H thymidine incorporation. In the absence of insulin, no effect on thymidine uptake by BRCE was observed when glucose concentration was rapidly altered, either increased or decreased. The stimulating effect of insulin on retinal capillary endothelin was more pronounced in log-phase cells than in stationary-phase cells. The extent of stimulation by insulin decreased with increasing glucose concentrations. This effect was not observed when osmotic pressure was increased by mannitol. The results of our experiments make it unlikely that altered osmotic stress, rapidly changing or abnormal glucose levels would be primarily responsible for altered endothelial activity. PMID- 1910120 TI - Gastric bleeding and increased gastric vascular permeability induced by platelet activating factor (PAF): effect of drugs that affect arachidonate metabolism. AB - The injurious effect of platelet activating factor (PAF) on gastric mucosa was studied by measuring bleeding in the acid perfused stomach of anesthetized rats. The effect of PAF on gastric mucosal vascular permeability (GMVP) was assessed by dye-leakage in the saline perfused stomach of anesthetized rats. Intravenous infusion of PAF (100 ng/kg/min for 20 min) apparently caused gastric bleeding under the gastric luminal perfusion with 150 mM HCl solution,, with the peak response at 50-70 min; biopsy indicated the presence of mucosal lesions. GMVP was markedly increased with the peak response at 20-40 min. Pretreatment with CV-3988 (1 or 10 mg/kg, i.v.), a PAF antagonist, dose-dependently blocked the PAF-induced gastric bleeding and increase in GMVP. Pretreatment with hydrocortisone acetate (20 or 40 mg/kg, s.c.) reduced PAF-induced gastric bleeding and increase in GMVP, in contrast to the aggravation by caffeic acid (1 or 5 mg/kg, s.c.). Indomethacin (1 or 5 mg/kg, s.c.) prevented PAF-induced gastric bleeding, and it depressed the increase in GMVP in the case of the lower dose. Prostaglandin E2 (50 or 500 micrograms/kg, s.c.) significantly reduced PAF-induced gastric bleeding, but had little effect on PAF-induced increase in GMVP. 1-Benzylimidazole (10 or 50 mg/kg, s.c.) also inhibited PAF-induced gastric bleeding and depressed the increase in GMVP at the higher dose. These results suggest that increased GMVP plays a significant role in producing the gastric damage by PAF. Changes in the mucosal level of cyclooxygenase products, especially thromboxanes, by drugs modifying the arachidonate metabolism would be closely associated with their prevention or aggravation of gastric damage induced by PAF. PMID- 1910122 TI - [Serum sensitivity of Pseudomonas aeruginosa isolated from sputum as a virulence factor in the lower respiratory tract]. AB - To elucidate the clinical significance of serum-sensitivity of respiratory pathogenic Pseudomonas aeruginosa (P. aeruginosa) strains, we examined serum sensitivity of P. aeruginosa isolated from 16 patients with lower respiratory tract infections and clinical backgrounds of these patients. We also evaluated the virulence of four serum-resistant and four serum-sensitive P. aeruginosa strains in murine pneumonia model induced by intratracheal challenge, and the silver-stained profiles of purified lipopolysaccharide (LPS) from these strains. Serum-sensitive strains were isolated only from patients with chronic bronchitis, bronchiectasis, and diffuse panbronchiolitis colonized with P. aeruginosa, and rarely caused pneumonias, while serum-resistant strains caused pneumonias in some cases. Intratracheal challenge of mice with 5 x 10(7) cfu per mouse of a serum resistant strain caused fatal hemorrhagic pneumonia with bacteremia. In contrast, the same dose of a serum-sensitive strain provided non-fatal pneumonia without bacteremia. LD50 of serum-sensitive strains in a murine model of P. aeruginosa pneumonia were at least 2-10 times higher than those of serum-resistant strain. The LPS profiles of two serum-resistant strains and one serum-sensitive strain showed ladder-like patterns. The similar analysis demonstrated that one serum sensitive strain was lack of ladder-like patterns. These data support that serum sensitive P. aeruginosa strains are less virulent than serum-resistant P. aeruginosa strains in the lower respiratory tract, and serum sensitivity of P. aeruginosa strains is determined by the structure of the O-side chain of LPS; either lack of the O-side chain or the presence of sparse O-side chain. PMID- 1910121 TI - [A clinical study of twelve cases of drug-induced pneumonitis]. AB - Twelve cases of drug-induced pneumonitis were clinically investigated. Treatment of antimicrobial agents in 8 cases of drug-induced pneumonitis ranged from 7-21 days (mean 12 days) and that of other drugs in 4 cases from 18-150 days (mean 70 days). The patients developed fever and dyspnea at a high rate of frequency. Abnormal laboratory findings included increased IgE (44%), eosinophilia (36%), and increased GOT and GPT in 33%. Chest X-ray films revealed a large reticulo nodular or ground glass shadows in both lung fields. The results of lymphocyte stimulation tests were positive in 5 of 11 cases (45%). Eight cases demonstrated a rapid improvement by discontinuation of the drug and corticosteroid was administered in 4 cases. The drug received by the patient and their known risk of pulmonary toxicity should be kept in mind in order to reach a diagnosis of drug induced pneumonitis and grasp the clinical picture of this disease. A provocation test is potentially dangerous, therefore it should not be carried out lightly. PMID- 1910124 TI - Differential gene expression in the recovery from ischemic renal injury. AB - Recovery from renal ischemia requires regeneration of damaged tubular epithelium. Previous studies have examined the expression of proto-oncogenes and growth factors after ischemia, but the response of genes coding for structural and functional genes has not been scrutinized. Rats were subjected to 40 minutes of renal artery occlusion and 60 minutes to 96 hours of reperfusion. Total RNA was isolated and mRNA for the structural protein actin, the enzymes superoxide dismutase and renin, the proto-oncogene c-fos, the nuclear protein histone H2b, and the putative marker for cell injury TRPM-2 was quantitated by Northern hybridization. Expression of the proto-oncogene c-fos was seen early but for only short duration. Histone gene expression was not markedly increased until 24 hours after ischemia, but remained increased for several days. Renin mRNA was undetectable one hour after ischemia, but was present in normal amounts at 24 and 48 hours. In contrast, superoxide dismutase mRNA was present in decreased amounts 24, 48, and 96 hours after ischemia. TRPM-2 gene expression was greatly increased 24 to 72 hours after ischemia and began decreasing at 96 hours. This selective sequence of gene expression or repression after renal ischemia might maximize the proliferative repair process. This information will be useful for designing therapies to further enhance recovery from acute renal injury. PMID- 1910125 TI - Urinary procoagulant and fibrinolytic activity in human glomerulonephritis. Relationship with renal function. AB - Fibrin deposition in kidney is a common event in some forms of human and experimental glomerulonephritis, and is thought to result from local activation of blood coagulation and/or impaired removal by the fibrinolytic system. We studied the urinary procoagulant and fibrinolytic activities in 46 patients with renal disease (26 with IgA nephritis, 13 with other forms of glomerulonephritis and 7 with non-inflammatory kidney disease) and in 15 matched healthy subjects, as possible indicators of the coagulation-fibrinolysis balance in kidney. Procoagulant activity was slightly but not significantly increased in patients with serum creatinine levels higher than 1.5 mg/dl (group II) as compared with patients with normal creatinine (group I) and controls. It was identified as tissue factor by biological criteria (dependence on factor VII). Fibrinolysis studies showed that both plasminogen activator activity and urokinase antigen were significantly lower in group II than in group I patients and controls (P less than 0.0005). Reduced fibrinolytic activity in patients' urine was due to decreased excretion of urokinase since no inhibitor was detected by both fibrin autography and functional assay. No differences were found between patients and controls in plasma fibrinolytic activity, plasminogen activator inhibitor, and procoagulant activity of blood monocytes. The urinary changes in severe renal disease may reflect an unbalance of the coagulation-fibrinolysis equilibrium in kidney and might be of pathogenetic and clinical relevance. PMID- 1910123 TI - Functional and structural alterations of the glomerular permeability barrier in experimental galactosemia. AB - Experimental galactosemia, induced by feeding rats a galactose enriched diet, reproduces many of the neural and ocular complications of diabetes and induces protein glycation and polyol accumulation. To explore the role of these biochemical abnormalities in the pathogenesis of glomerular injury, adult male Sprague-Dawley rats were placed on either a 50% galactose or 50% glucose diet. After two months, galactose fed rats exhibited elevated excretory rates of protein, albumin, and IgG. Blebbing and ballooning of the glomerular epithelial cells were apparent in rats on the galactose supplemented diet. Morphometric evaluation of the glomeruli revealed an increase in the fractional and absolute volume of the glomerular epithelial cells, but glomerular and mesangial volume, basement membrane thickness, and epithelial foot process width were similar on the two diets. Glycation of the glomerular basement membrane was increased in the galactose fed rats. Glomerular micropuncture revealed similar glomerular pressures and flow rates on the two diets. Aldose reductase inhibition had no effect on galactose induced proteinuria. These results suggest that biochemical abnormalities such as protein glycation may be important in the pathogenesis of altered glomerular permselectivity in diabetic nephropathy. PMID- 1910126 TI - [A case of a congenital diverticulum of the urethra combined with calculosis]. AB - A rare case of congenital diverticulum of the urethra of a 14-year-old boy associated with numerous calculi is reported. The clinical symptoms were pain during micturition and dysuria. Physical examination was complemented by instrumental, of which most important for the diagnosis was retrograde urethrography and urethrocystoscopy. Diverticulotomy and suprapubic derivation of urine were made. PMID- 1910127 TI - Therapy of advanced acute myeloblastic leukemia with cytarabine and interleukin 2. AB - A child with acute myelogenous leukemia who relapsed three months after an allogeneic bone marrow transplant received intermediate-dose cytarabine followed by interleukin 2 (IL-2). Complete remission was achieved after the first cycle of IL-2. Five more combined cycles of cytarabine and IL-2 were given over the next year, during which remission has persisted. IL-2 therapy affected serum tumor necrosis factor (TNF), interferon gamma (IFN gamma) and soluble IL-2 receptor (sIL-2r) levels. In vitro cytotoxicity against leukemia cell lines and recipient leukemia cells was also increased. PMID- 1910128 TI - Neurologic syndromes and prolonged survival: when can artificial nutrition and hydration be forgone? PMID- 1910130 TI - Cruzan: facing the inevitable. PMID- 1910129 TI - The process of dying with and without feeding and fluids by tube. PMID- 1910131 TI - The long dying of Nancy Cruzan. PMID- 1910132 TI - [Enterococcus faecalis bacteremia]. AB - BACKGROUND: This study was prompted by the increasing role of E. faecalis in hospital acquired infections, their morbidity and mortality and the development of resistances. The aim of the study was to define the epidemiological features, the predictive factors of bacteremia and the mortality prognosis in a group of patients with E. faecalis bacteremia. METHODS: The clinical and epidemiological features on admission, after 3 days and one week of therapy and one month after therapy were evaluated in 57 cases of true E. faecalis bacteremia. The effectiveness of therapy was assessed by the rate of clinical and microbiological cures, deaths and survivals. RESULTS: The incidence of E. faecalis bacteremia was 5.9%. 78% of them were hospital acquired, with unknown source in 31%. Generally, they developed in surgical services and usually the patients had received antibiotic treatment or instrumentation. 63% of bacteremias were monomicrobial. Male sex, hospitalization (particularly in surgical or intensive care services), underlying disease of rapidly fatal prognosis, the previous use of third generation cephalosporins and/or ciprofloxacin, and previous instrumentation or surgery were found to be predictive factors of bacteremia. On the other hand, underlying disease with rapidly fatal prognosis, with initial poor or critical clinical condition, the previous use of wide spectrum antibiotics, polymicrobial bacteremia, and the presence of leukocytosis or complications were significantly associated with a higher mortality. The resistance rates ranged between 42% to kanamycin and 1% to amikacin. CONCLUSIONS: In view of the results, a better knowledge of the predictive and prognostic factors of E. faecalis bacteremia is required for prevention and treatment. PMID- 1910133 TI - [Acute suppurative arthritis: an unusual manifestation of murine typhus (endemic)]. AB - A 37-year-old patient had fever, diffuse maculopapular rash and acute suppurative arthritis of both knees, which was totally cured with doxycycline without sequelae. Skin biopsy showed characteristic findings of rickettsiosis. In the serological investigation the Weil-Felix reaction was positive and antibodies against Rickettsia typhi but not against Rickettsia conorii were detected by indirect immunofluorescence. No similar case has found in the reviewed literature. PMID- 1910135 TI - In situ testing of CO2 laser on dental pulp function: effects on microcirculation. AB - The effect of CO2 laser irradiation on pulpal microcirculation was studied in cat canines. The enamel surfaces of 4 teeth were exposed with energy densities of 304 1440J/cm2, using either a handpiece or a microslad, with a focal spot of 0.21mm and 0.33mm respectively. Pulpal blood flow (PBF) before and following lasing was recorded through the intact tooth surface by a laser Doppler flowmeter. CO2 laser irradiation caused an increase in PBF, which was immediate and transient. The PBF increase was higher in a large pulp than in a small pulp, and it was inversely related to the focal spot size. These findings confirm that the dental pulp is thermally affected by CO2 lasing of the tooth surface, however, without extensive pulp coagulation. It is concluded that the effects of laser irradiation on the pulpal microcirculation may be studied in situ by means of the presented methodology. PMID- 1910134 TI - Comparison of four laser types for experimental pain stimulation on oral mucosa and hairy skin. AB - The use of different lasers for stimulation in human experimental pain research has provided a sensitive method for evaluation of thin nerve fiber functions. In this study, sensory and pain thresholds were compared to argon-, copper vapour-, Nd:YAG-, and CO2 laser stimulation on hairy skin and on oral mucosa. The influence on thresholds with respect to laser type, stimulation site, surface colour, and stimulus parameters (laser beam diameter and pulse duration) was investigated. Significant differences in thresholds between the four lasers were found on both surfaces; however, no significant differences existed between thresholds on the skin and on the tongue when the same laser was used. The observations imply that wavelength-dependent optical properties of the stimulated tissue influence on threshold determinations. Furthermore, the results indicate that temporal and spatial summation mechanisms may exist for laser induced warmth and pain perceptions. Laser stimulation may be a new tool for the investigation of origin and genesis of various orofacial pain syndromes. PMID- 1910136 TI - Nd:YAG laser hyperthermia treatment of rat mammary adenocarcinoma in conjunction with surface cooling. AB - Electromagnetic radiation ranging from radiofrequency to microwave has classically been used to induce hyperthermia for treatment of cancer. This paper presents a new technique using near infrared radiation from an Nd:YAG laser in conjunction with surface cooling to induce hyperthermia in a rat tumor model. A CW Nd:YAG laser hyperthermia system was used to induce hyperthermic temperatures in chemically (DMBA) induced rat mammary adenocarcinomas. The laser was interfaced to a computer and a thermometry unit that provided feedback to control the tumor temperature between 43.2-43.5 degrees C. A thermocouple was placed at the base of the tumor and its temperature was used to control laser exposure. All tumors were 10 to 20 mm in diameter. Surface cooling methods investigated included forced air flow from a fan, forced oxygen flow plus an IV drip, and forced moist oxygen flow from a nebulizer. Twelve rat mammary adenocarcinomas have been treated with Nd:YAG laser hyperthermia. In 4 treatments, no surface cooling was employed. In one treatment the surface was cooled using oxygen flow plus IV drip. In 7 treatments the skin was cooled using the nebulizer technique. The nebulization provided the most effective and reproducible surface cooling. Nd:YAG laser hyperthermia delivered in conjunction with nebulizer surface cooling produced efficient heating of rat mammary adenocarcinomas. A mean temperature of 42.1 degrees C was obtained at the base of the tumors while the mean surface temperature was 37.0 degrees C. PMID- 1910137 TI - Possible modulation of N-methyl-D,L-aspartic acid induced prolactin release by testicular steroids in the adult male rhesus monkey. AB - N-methyl-D,L-aspartic acid (NMA), an agonist of the neurotransmitter glutamate has been shown to acutely stimulate the release of prolactin (PRL) in intact rats and monkeys. To further investigate the role of neuroexcitatory amino acids in PRL secretion, the effects of NMA administration were examined on PRL release in long term orchidectomized adult rhesus monkeys, in both the absence and presence of testosterone. Intact and long term castrated adult male monkeys weighing between 8-13 kg, were implanted with a catheter via the saphenous vein for blood withdrawal and drug infusion. Blood samples were collected at 10 min intervals for 50 min before and 70 min after administration of the drug or vehicle. Plasma PRL concentrations were estimated using radioimmunoassay. Whereas a single iv injection of NMA (15 mg/kg BW) induced a prompt discharge of PRL in intact monkeys, an identical dose had surprisingly no effect on PRL secretion in orchidectomized animals. On the other hand, plasma PRL increases in response to a challenge dose of thyrotropin releasing hormone (TRH; 6 micrograms/kg BW, iv) were similar in magnitude in the two groups of monkeys. Testosterone replacement in orchidectomized animals by parenteral administration of testosterone enanthate (200 mg/wk) reinitiated the PRL responsiveness to acute NMA stimulation. These results indicate that N-methyl-D-aspartic acid (NMDA) dependent drive to PRL release in the adult male rhesus monkey may be overtly influenced by the sex steroid milieu. PMID- 1910139 TI - Substrate specificity and some properties of phenol sulfotransferase from human intestinal Caco-2 cells. AB - The phase II metabolic reactions, sulfation and glucuronidation, were studied in a human colon carcinoma cell line (Caco-2), which has been developed as a model of intestinal enterocytes. Phenol sulfotransferase (PST, EC 2.4.2.1) was isolated from Caco-2 cells cultured for 7, 14 and 21 days. The enzyme catalyzed the sulfation of both p-nitrophenol and catecholamines (e.g., dopamine) as well as most catecholamine metabolites. The affinity (Km) of PST for dopamine was much higher than for p-nitrophenol, and the specific activity of PST with both substrates increased with the age of the cells. The thermal stability of Caco-2 PST increased with cell age and was not dependent on the acceptor substrate used. The thermolabile PST from 7-day old cells was more sensitive to NEM than was the thermostable enzyme from 21-day old cells. No UDP-glucuronyltransferase (EC 2.4.1.17) activity was detected in 7-, 14- and 21-day old Caco-2 cells with any of the methods used. PMID- 1910138 TI - Effects of amphetamine on T-cell immune response in mice. AB - Mice chronically injected with amphetamine (0.4 mg/kg/day) showed a reduction in thymus and spleen cellularity, and in peripheral T lymphocyte population. The blastogenic response of spleen lymphoid cells was assessed and amphetamine was found to inhibit T-cell proliferation. Amphetamine also reduced the capacity of mice to the development and passive transfer of immunity to Listeria monocytogenes. PMID- 1910140 TI - [Group D streptococci and enterococci: identification, sensitivity to antibiotics and a study of the high level resistance to aminosides (Charles Nicolle Hospital in Tunis)]. AB - 197 strains of enterococcus and group D Streptococcus were isolated from human material at Charles Nicolle Hospital (Tunis) and identified by biochemical tests: 174, Enterococcus faecalis, 6 Enterococcus faecium, 2 Enterococcus durans and 15 Streptococcus bovis. The sensitivity to antibiotics was studied: all Enterococcus faecium were resistant at least to one antibiotic, 15% of Enterococcus faecalis were sensitive for all antibiotics tested the other species were frequently sensitive. High level resistance to aminoglycosides were frequent in Enterococcus faecalis 40%: among these strains high level resistance to gentamicin accounts for 12% and 18 frequently associated with resistance to kanamycin and streptomycin, this situation present therapeutic problems in case of severe infection. PMID- 1910143 TI - Long-term effects of vanadate treatment on glycogen metabolizing and lipogenic enzymes of liver in genetically diabetic (db/db) mice. AB - The effect of long-term (12 weeks) oral treatment with sodium orthovanadate on hepatic glycogen metabolizing and lipogenic enzymes was studied in genetically diabetic db/db mice. These mice were characterized by significant (P less than .001) obesity, hyperglycemia, and hyperinsulinemia. Vanadate administration led to significant decreases in body weight (P less than .001) and plasma insulin levels (P less than .01) and the mice became normoglycemic. The total glycogen synthase (EC 2.4.1.11) activity in the livers of diabetic mice showed a 47% increase, which did not undergo any significant change after treatment with vanadate. Hepatic phosphorylase (EC 2.4.1.1) activities (a and total) showed twofold increases in db/db mice when compared with the nondiabetic ones. Vanadate caused significant decreases in phosphorylase a (P less than .02) and total phosphorylase (P less than .001) activities. Glucose-6-phosphate dehydrogenase (EC 1.1.1.49) and malic enzyme (EC 1.1.1.40) in diabetic liver had differential alterations, as indicated by a 50% decrease in glucose-6-phosphate dehydrogenase and 160% increase in malic enzyme activities. Vanadate administration led to normalization of both enzyme activities. In nondiabetic mice, vanadate treatment did not cause changes in any parameter, except for a 46% decrease in plasma insulin levels. This investigation indicates that vanadate can normalize many of the metabolic abnormalities seen in the liver of genetically diabetic db/db mice, a model for non-insulin-dependent diabetes mellitus (NIDDM). Vanadate also causes a decrease in plasma insulin level, along with normalization of plasma glucose, which suggests a partial reversal of insulin resistance. PMID- 1910142 TI - Guinea-pig alveolar macrophages kill Mycobacterium tuberculosis in vitro, but killing is independent of susceptibility to hydrogen peroxide or triggering of the respiratory burst. AB - Alveolar macrophages from the lungs of guinea-pigs that had been vaccinated, boosted and then intravenously challenged with Mycobacterium microti or Mycobacterium bovis BCG killed tubercle bacilli phagocytosed in vitro. The killing was modest, about 40% of phagocytosed bacilli were killed in a day, but alveolar macrophages from animals that had been vaccinated and boosted but had not received the intravenous challenge did not kill bacilli. Different strains of tubercle bacilli had different degrees of susceptibility to these activated macrophages but there was no correlation between killing by macrophages and mycobacterial susceptibility to killing by hydrogen peroxide. The different strains of tubercle bacilli triggered peroxide release from these macrophages but there was no correlation with susceptibility to killing by macrophages or with virulence in the guinea-pig. However, phagocytic uptake of these strains by the activated macrophages was inversely correlated with virulence, and uptake by activated macrophages was less than uptake by normal macrophages. PMID- 1910145 TI - Severe flecainide overdose. PMID- 1910141 TI - Extracellular lipase of Pseudomonas aeruginosa: biochemical characterization and effect on human neutrophil and monocyte function in vitro. AB - Lipase was isolated from P. aeruginosa by ultrafiltration of sterile-filtered culture supernatant. Gel filtration on Sepharose 4B yielded a broad peak corresponding to a molecular mass range of 100 to 1000 kDa. Electron microscopy of a negatively stained lipase preparation after Sepharose 4B chromatography revealed spherical particles with diameters ranging from 5 to 20 nm. Biochemical characterization and SDS polyacrylamide gel electrophoresis suggested that these particles consisted of protein and carbohydrate including lipopolysaccharide with the major enzyme activity being lipase. Various concentrations of this lipase preparation were preincubated with human peripheral blood neutrophils and monocytes. The chemotaxis and chemiluminescence of these cells were then determined. It was shown that lipase inhibited the monocyte chemotaxis and chemiluminescence, whereas it had no or very little effect on neutrophils. The inhibitory effect was concentration dependent and was abolished by heat treatment of the enzyme at 100 degrees C. Since monocytes are one of the important cells of the host defence system the inhibition of the function of these cells may contribute to the pathogenesis of infections caused by P. aeruginosa. PMID- 1910146 TI - Nosocomial infection and pseudoinfection from contaminated endoscopes and bronchoscopes--Wisconsin and Missouri. AB - Flexible fiber-optic endoscopes are widely used in the United States for diagnostic and therapeutic procedures. Between uses, endoscopes should be cleaned and disinfected either manually or by using automated machines. However, outbreaks have occurred among patients exposed to contaminated endoscopes or to inadequately disinfected bronchoscopes (1-4). This report summarizes one outbreak of nosocomially acquired infection (Wisconsin) and one of pseudoinfection (Missouri) linked to endoscopes contaminated during cleaning and disinfection by automated reprocessing machines. PMID- 1910147 TI - The mkaC virulence gene of the Salmonella serovar typhimurium 96 kb plasmid encodes a transcriptional activator. AB - The intracellular growth and virulence of Salmonella serovar Typhimurium for mice is dependent on a plasmid-borne gene cluster termed mka. We studied the regulatory interactions of the genes mkaA, mkaB, mkaC and mkaD using lacZ gene fusions. Complementation experiments with cloned DNA fragments encoding each of the four MKa proteins indicated that mkaC enhances the expression of beta galactosidase from the mkaA-, mkaB- and mkaC-lacZ gene fusions in trans. An mkaD lacZ fusion or mkaA-lacZ fusion that did not contain DNA proximal to mkaB was not inducible with MkaC, indicating that at least mkaB and mkaA are induced together as an operon. MkaC is thus the first virulence protein whose function has been resolved. PMID- 1910144 TI - [Effect of the artificial electron acceptor reumycin on the nature of an intermediate accumulated by Pseudomonas aeruginosa bacteria]. AB - We investigated the effect of the autooxidizable electron acceptor reumicin on the oversynthesis of intermediates by the bacterium Pseudomonas aeruginosa during its growth limitation by a nitrogen source. Addition of reumicin which accepted the reducing equivalents from NADH(+)-dehydrogenase of the respiratory chain was shown to reduce the rate of alpha-ketoglutarate formation and yield, and to induce the synthesis and excretion of pyruvate into the cultivation medium. The maximal accumulation of pyruvate was observed when reumicin was added at a concentration of 0.4-0.5 mM. It is concluded that the nature of the overproduced intermediate, the rate of its biosynthesis and yield depend on the extent of reducibility of the pyridine nucleotide pool. The oversynthesis of alpha ketoglutarate is suppressed by chloramphenicol, a protein synthesis inhibitor, which points to a possible involvement of inducible systems including the carriers of the acids via the cytoplasmic membrane. PMID- 1910148 TI - The Mycobacterium tuberculosis shikimate pathway genes: evolutionary relationship between biosynthetic and catabolic 3-dehydroquinases. AB - The Mycobacterium tuberculosis shikimate pathway genes designated aroB and aroQ encoding 3-dehydroquinate synthase and 3-dehydroquinase, respectively were isolated by molecular cloning and their nucleotide sequences determined. The deduced dehydroquinate synthase amino acid sequence from M. tuberculosis showed high similarity to those of equivalent enzymes from prokaryotes and filamentous fungi. Surprisingly, the deduced M. tuberculosis 3-dehydroquinase amino acid sequence showed no similarity to other characterised prokaryotic biosynthetic 3 dehydroquinases (bDHQases). A high degree of similarity was observed, however, to the fungal catabolic 3-dehydroquinases (cDHQases) which are active in the quinic acid utilisation pathway and are isozymes of the fungal bDHQases. This finding indicates a common ancestral origin for genes encoding the catabolic dehydroquinases of fungi and the biosynthetic dehydroquinases present in some prokaryotes. Deletion of genes encoding shikimate pathway enzymes represents a possible approach to generation of rationally attenuated strains of M. tuberculosis for use as live vaccines. PMID- 1910152 TI - Toxic effects of interleukin-2-activated lymphocytes on vascular endothelial cells. AB - IL-2-activated lymphocytes (LAK cells) show increased adherence to, and killing of, human vascular endothelial cells compared to resting lymphocytes. In the present work, we have found that supernatants from LAK cell cultures also are toxic to human umbilical vein endothelial cells (HUVEC) when tested for 48 h in a neutral red uptake assay. Recombinant TNF-alpha and IFN-gamma at high concentrations are also toxic under the same test conditions, and TNF-alpha was directly detected in LAK cell supernatants. An inconsistent inhibition of toxicity was found with anti-TNF-alpha whereas anti IFN-gamma antibodies had a partial inhibitory effect. The susceptibility of HUVEC to cellular killing by LAK cells could be up- and down-regulated with insulin-like growth factor I and IFN gamma, respectively. It is concluded that damage to vascular endothelium during high dose IL-2 treatments may be partially related to an excessive production of lymphokines such as IFN-gamma and TNF-alpha. IFN-gamma may, in addition, be protective for HUVEC during cellular interactions with LAK cells. PMID- 1910149 TI - Identification of the genes coding for the second-largest subunits of RNA polymerases I and III of Drosophila melanogaster. AB - We have isolated cDNA and genomic clones of Drosophila melanogaster by cross hybridization with a 658 bp fragment of the yeast gene coding for the second largest subunit of RNA polymerase III (RET1). Determination of the sequence by comparison of genomic and cDNA regions reveals an ORF of 3405 nucleotides which is interrupted in the genomic sequence by an intron of 48 bp. The deduced polypeptide consists of 1135 amino acids with a calculated molecular weight of 128 kDa. The protein sequence shows the same conserved regions of homology as those observed for all the second-largest subunits of RNA polymerases cloned so far. The gene (DmRP128) obviously codes for a second-largest subunit of an RNA polymerase which is different from DmRP140 and DmRP135. We have purified three distinct RNA polymerase activities from D. melanogaster. By using specific RNA polymerase inhibitors in enzyme assays and by comparing their subunit composition we were able to distinguish between RNA polymerase I, II, and III. RNA polymerase preparations of D. melanogaster were blotted and the second-largest subunits were identified with antibodies raised against polypeptides expressed from DmRP128 and DmRP135. Anti-DmRP135 antibodies react strongly with the second-largest subunit of RNA polymerase I but do not react with the respective subunits of RNA polymerase II and III. The second-largest subunit of RNA polymerase III is only recognized by anti-DmRP128. Previously, we have claimed that DmRP135 codes for the second-largest subunit of RNA polymerase III.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1910151 TI - Induction and cleavage of Salmonella typhimurium UmuD protein. AB - SOS mutagenesis in prokaryotes is dependent upon the inducible activity of the chromosomally encoded UmuDC proteins, or homologous proteins such as MucAB or ImpCAB which are found on naturally occurring plasmids. Relative to Escherichia coli, however, Salmonella typhimurium is much less responsive to the mutagenic effects of DNA-damaging agents, despite the fact that it possesses both chromosomally and plasmid encoded umu-like operons. In E. coli, activation of the UmuD mutagenesis protein to UmuD' via RecA-mediated proteolysis is a critical step in the mutation fixation pathway. We have used a polyclonal antiserum raised against the E. coli UmuD and UmuD' proteins to show that S. typhimurium expresses cross-reacting material only after treatment with the DNA-damaging agent mitomycin C. The S. typhimurium umuDC operon, therefore, appears to be regulated by mechanisms similar to the E. coli umuDC operon. After induction, the S. typhimurium UmuD protein was processed to UmuD' in both S. typhimurium and E. coli. However, the S. typhimurium UmuD protein appears to be cleaved more efficiently than the E. coli UmuD protein under similar conditions. The data suggest that conversion of UmuD to the mutagenically active UmuD' is not the rate limiting factor accounting for the weakly mutable phenotype of S. typhimurium. PMID- 1910153 TI - Inhibition of early atherogenesis in transgenic mice by human apolipoprotein AI. AB - Epidemiological surveys have identified a strong inverse relationship between the amount in the plasma of high density lipoproteins (HDL), apolipoprotein AI (ApoA I), the major protein component of HDL, and the risk for atherosclerosis in humans. It is not known if this relationship arises from a direct antiatherogenic effect of these plasma components or if it is the result of other factors also associated with increases in ApoA-I and HDL levels. Because some strains of mice are susceptible to diet-induced formation of preatherosclerotic fatty streak lesions, and because of available techniques for the genetic manipulation of this organism, the murine system offers a unique setting in which to investigate the process of early atherogenesis. To test the hypothesis that induction of a high plasma concentration of ApoA-I and HDL would inhibit this process, we studied the effects of atherogenic diets on transgenic mice expressing high amounts of human ApoA-I. We report that transgenic mice with high plasma ApoA-I and HDL levels were significantly protected from the development of fatty streak lesions. PMID- 1910150 TI - The KNS1 gene of Saccharomyces cerevisiae encodes a nonessential protein kinase homologue that is distantly related to members of the CDC28/cdc2 gene family. AB - A novel protein kinase homologue (KNS1) has been identified in Saccharomyces cerevisiae. KNS1 contains an open reading frame of 720 codons. The carboxy terminal portion of the predicted protein sequence is similar to that of many other protein kinases, exhibiting 36% identity to the cdc2 gene product of Schizosaccharomyces pombe and 34% identity to the CDC28 gene product of S. cerevisiae. Deletion mutations were constructed in the KNS1 gene. kns1 mutants grow at the same rate as wild-type cells using several different carbon sources. They mate at normal efficiencies, and they sporulate successfully. No defects were found in entry into or exit from stationary phase. Thus, the KNS1 gene is not essential for cell growth and a variety of other cellular processes in yeast. PMID- 1910154 TI - Exercise in hemodialysis patients after treatment with recombinant human erythropoietin. AB - To assess the effect of substantial increases in blood hemoglobin (Hb) caused by treatment with recombinant human erythropoietin (rhEPO) on exercise capacity in maintenance hemodialysis patients, we evaluated 10 patients (7 men and 3 women) at a mean age of 44.3 +/- 8.4 years on maintenance hemodialysis for a mean of 29.7 +/- 30.2 months by treadmill exercise to exhaustion. The patients were tested before administration of rhEPO and after a minimum 1 g/dl rise in Hb. With a change in Hb from 7.1 +/- 1.4 to 9.8 +/- 2.1 g/dl, peak oxygen consumption (VO2 peak) with exercise increased 50.3 +/- 9% (T1 = 15.1 +/- 5.3, T2 = 22.7 +/- 4.6 ml O2/kg/min, p less than 0.05). Respiratory exchange ratio (RER) at a given submaximal exercise level (3 mph, 6% of elevation) decreased significantly (T1 = 1.13 +/- 0.24, T2 = 0.92 +/- 0.08, p less than 0.05). The rhEPO-mediated increase in Hb was associated with an increased VO2 peak--an improvement of the peak exercise capacity and a reduced submaximal RER--reflecting a reduction in anaerobic metabolism at activities of daily living. PMID- 1910155 TI - Hypertonic mannitol ameliorates intracompartmental tamponade in model compartment syndrome in the dog. AB - Acute compartment syndrome (ACS) is a devastating complication of rhabdomyolysis caused by muscle tamponade secondary to increased intracompartmental pressure (Pi). ACS requires emergency surgical decompression when Pi greater than 30 mmHg (normal less than 4.0 mmHg) and clinical signs exist. The present study was undertaken to examine whether mannitol which has been used extensively for prevention of acute renal failure in rhabdomyiolysis may also improve muscular hemodynamics in ACS. ACS was produced in dogs by injecting dog plasma into the anterolateral compartment of the hind limb. The Pi was directly monitored. Control dogs received saline, whereas experimental dogs received intravenously 20% mannitol (0.15 ml/min/kg) over a period of 1 h. The initial Pi was set arbitrarily at 100 mm Hg. Following the establishment of ACS, the spontaneous mean decrease in Pi in the control group was 40% of initial value over 60 min (n = 5) versus a decrease of 65%/60 min in the experimental (mannitol) group (n = 7, p less than 0.01). The net mean decompressive effect of mannitol treatments was approximately 28 mm Hg (mean control Pi minus mean experimental Pi at time 60 min). Extrapolated to man with ACS, such a decrease in Pi induced by mannitol theoretically could relieve compartmental tamponade noninvasively. PMID- 1910156 TI - Expression of synaptophysin during the prenatal development of the rat spinal cord: correlation with basic differentiation processes of neurons. AB - The development of the spinal cord involves the proliferation of neurons, their migration to well-defined areas, fiber outgrowth and synapse formation. The present study was designed to correlate the spatiotemporal pattern of expression of synaptophysin, an integral membrane protein of small synaptic vesicles, with these basic processes occurring during the embryonic development of the rat spinal cord. Thoracic segments of spinal cords from embryonic days 12, 14, 16, 18, 20 and of adult spinal cords were studied. S1 nuclease protection assays and immunoblots revealed minute amounts of specific mRNA and synaptophysin at embryonic day 12. There was a steep increase of mRNA between embryonic days 14 and 16, after which levels reached a plateau. A rise in the amount of synaptophysin in the spinal cord occurred between embryonic days 12 and 14, and the levels changed only slightly until the end of embryonic development. Even higher levels of synaptophysin, found in the adult spinal cord, may indicate that its biosynthesis continued after birth. In situ hybridization histochemistry revealed the localization of specific synaptophysin mRNA in the neuroepithelium. However, immunocytochemistry failed to detect synaptophysin in the neuroepithelial cells. Following migration of the neuroblasts, synaptophysins was found in neurons concomitantly with the onset of fiber outgrowth. Thus, already at embryonic day 12, outgrowing fibers of the dorsal root sensory neurons and of motoneurons were synaptophysin positive. From embryonic day 14 throughout the prenatal period, strong synaptophysin immunoreactivity was seen in the ventrolateral and dorsal parts of the marginal layer. Most likely this staining pattern indicates transient functional synaptic contacts because, in the adult spinal cord, the corresponding region, the white matter, exhibited only faint synaptophysin immunoreactivity. In the intermediate layer of the embryonic spinal cord, which corresponds to the gray matter of the adult spinal cord, synaptophysin-positive fibers were observed prior to the formation of functional synapses. The latter are most likely permanent, since synaptophysin in the adult spinal cord is mainly confined to the gray matter. Our data (i) show transcription and translation of synaptophysin within the neurons of the spinal cord and correlate these processes with proliferation, migration, fiber outgrowth and the formation of transient or permanent synapses, and (ii) prove that synaptophysin is a marker for fiber outgrowth in addition to synapse formation. PMID- 1910157 TI - Indomethacin prevents ventilation-induced decreases in pulmonary vascular resistance of the middle region in fetal lambs. AB - Previously, we report that the major site of pulmonary vascular resistance in fetal lambs occurred in the middle region defined by vascular occlusion, and that this region exhibited the greatest decrease upon ventilation with O2. To assess the relative individual contributions of ventilation and oxygenation to this decrease, we determined the distribution of pressures across the pulmonary circulation in isolated perfused lungs from 20 fetal lambs (131 - 137 d gestation) by inflow and outflow vascular occlusions. A membrane oxygenator was included in the extracorporeal circuit to control the PO2 at 4 kPa (30 torr) in the unventilated fetal lungs. Half of the fetal lungs were ventilated first without changing the initial gas tensions, and the others were oxygenated first by changing the initial gas tension to a hyperoxic mixture [PO2 = 26.6 kPa (200 torr)] without ventilation. Finally, both groups of lungs were ventilated and oxygenated. In addition, indomethacin was added to the perfusate (0.112 mM, or 40 micrograms/mL) in half of the preparations in each group to determine the effect of prostaglandins on the distribution of pressures during these conditions. The decrease in the total pulmonary vascular resistance with ventilation and/or oxygenation was primarily due to changes in the middle pressure gradient (delta Pm). In fetal lungs without indomethacin, ventilation without oxygenation reduced delta Pm from 6.1 +/- 0.8 to 2.5 +/- 1.0 kPa, or 74% of the total ventilation- and oxygenation-induced decrease in delta Pm (final value = 1.2 +/- 0.6 kPa).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1910159 TI - Adaptation to taurine deprivation in the phosphate-depleted rat. AB - The nonessential amino acid taurine, which is inert in renal tissue, was used to study renal adaptation in the presence of phosphate (P) depletion in the rat. Weanling rats were placed on the control diet (0.7% P, normal taurine) for 4 wk, then fed one of the experimental diets or continued on the control diet for 1 wk. The diets used were 1) P+T- (0.7% P, low taurine), 2) P-T+ (0.1% P, normal taurine); and 3) P-T- (0.1% P, low taurine). Taurine deficiency was associated with avid tubular reabsorption of taurine, irrespective of P status. This was associated with a 4- to 5-fold increase in the Vmax of uptake (p less than 0.001). On the other hand, P depletion increased the Km of taurine uptake by 6.6- to 9.5-fold, suggesting a decrease in the affinity of the taurine symport (p less than 0.001). This was independent of the taurine status of the animals. Although there was no effect of diet on the urinary excretion of beta-alanine, P depletion, irrespective of taurine status, resulted in a 2-fold increase in the Km of beta-alanine uptake. We conclude that the taurinuria of P depletion is reversed in taurine deprivation. The adaptive response involves an increase in the Vmax of uptake. However, the increase in Km of taurine uptake observed in P depletion does not reverse with taurine depletion. PMID- 1910158 TI - Vascular lactic acid infusions do not alter the incidence of fetal breathing movements or their inhibition by acute hypoxemia. AB - Hypoxemia transiently inhibits the incidence of fetal breathing movements (FBM), but their incidence returns to normal after several hours despite maintained hypoxemia. We hypothesized that the lactic acidosis associated with prolonged systemic hypoxemia might mediate the adaptation of the hypoxemic inhibition of FBM. In sheep fetuses, the incidence of FBM was measured in a control hour and during 6 h of i.v. infusion of L-lactic acid, which raised the blood lactate concentrations to levels seen with moderate hypoxemia. FBM were observed at the same incidence as during control during each of the first 4 h (all approximately 40%). In the 5th h of lactic acid infusion, fetal hypoxemia was induced by lowering maternal inspired oxygen fraction and FBM occurred only 8 +/- 1% (SEM) of that hour. In a subsequent normoxemic recovery hour, the incidence of FBM remained below control levels. In the same animals on a different day, a similar hypoxemia induced without the acid infusion caused a comparable inhibition of FBM, but the incidence of FBM returned to the control level in a subsequent recovery hour. A moderate peripheral lactic acidosis does not blunt the inhibition of FBM evoked by acute hypoxemia and is not a likely explanation for the return of FBM during prolonged hypoxemia but actually might mediate some of the inhibition. PMID- 1910160 TI - Effects of maternal diabetes or in vitro hyperglycemia on uptake of palmitic and arachidonic acid by rat embryos. AB - Altered transfer of nutrients from mother to conceptus may be involved in the pathogenesis of the developmental disturbances in offspring of diabetic mothers. In our study, the embryonic uptake of a saturated (palmitic acid) and a nonsaturated (arachidonic acid) fatty acid was evaluated in a normal and a diabetes-like environment under in vivo and in vitro conditions that yield growth retardation and somatic malformations in the embryos. The palmitic acid uptake in embryos from diabetic rats and in embryos cultured in vitro in 30 mmol/L D glucose did not differ from the respective controls. Only embryos cultured in the highest D-glucose concentration (60 mmol/L) showed slightly increased uptake, which suggests that alterations in palmitic acid transfer have no role in the processes of embryonic maldevelopment in diabetic pregnancy. In contrast, the results showed that a diabetes-like environment both in vivo and in vitro causes increased embryonic uptake of arachidonic acid. Consequently, if the teratogenic mechanisms of diabetic pregnancy involve decreased embryonic levels of arachidonic acid, as has been suggested, this would not be the effect of a decreased uptake per se, but rather of an altered intracellular metabolism or decreased extracellular availability of this fatty acid. PMID- 1910161 TI - CO2 production, body temperature, and ventilation in hypoxic newborn cats and dogs before and after body warming. AB - Many newborn mammals decrease metabolism and body temperature (Tb) during acute hypoxia. We asked what effects warming of the hypoxic newborn would have on these variables. In unanesthetized newborn cats and dogs, we measured the breathing pattern, CO2 production, Tb, and ambient temperature during normoxia at an ambient temperature of 28 degrees C, 30 min of hypoxia (10% O2), and an additional 30 min of hypoxia plus warming. During hypoxia, Tb and CO2 production decreased in both species, whereas the absolute value of ventilation did not change in kittens and increased in puppies. During hypoxia plus warming, Tb was gradually returned to the normoxic value by increasing ambient temperature by 3 to 4.5 degrees C. This increase did not modify CO2 production in either species, and it increased minute ventilation in kittens. We conclude that during hypoxia 1) warming the newborn can increase Tb, but not metabolism, to the normoxic value; 2) the decrease in Tb is not a causative prerequisite of the hypoxia hypometabolism; and 3) an artificial increase in Tb to the normoxic value can stimulate minute ventilation, probably because it is perceived as an hyperthermic stimulus. PMID- 1910163 TI - Can clinical judgment detect children with speech-language problems? PMID- 1910162 TI - Effectiveness of computer-generated appointment reminders. AB - Previous studies of appointment reminders among general pediatric patients have been done exclusively among low socioeconomic populations in clinics with low continuity of care and using block scheduling methods. This study of mailed computer-generated appointment reminders took place in a setting with patient demographics and practice techniques similar to those of many private pediatric practices. During a 6-month period, 901 appointments that were made more than 7 days prior to the scheduled date were randomly assigned to receive reminder postcards or to serve as controls. The overall broken appointment (no-show) rate was reduced from 19% in the control group to 10% in the reminder group, representing a 48% reduction (P = .0002). The magnitude of reduction of no-shows was similar for appointments scheduled more than 14 days prior to the appointment time (39%) as well as those scheduled more recently (58%). Equivalent results were seen with well-child appointments (47%) as with other visits (50%). Both lower and higher socioeconomic groups demonstrated similar results. The mailed postcards cost $0.20 each and were highly cost effective, generating an estimated $7.50 for each $1 spent during the study. With reductions similar to those found in this study, computer-generated appointment reminders are likely to be cost effective in other practices if current no-show rates are greater than 2% to 4%. PMID- 1910164 TI - The Journal of Infection Control Nursing. Use and abuse of glutaraldehyde. PMID- 1910167 TI - [Evaluation of platelet malondialdehyde and 12-hydroperoxyeicosatetraenoic acid in type I and II diabetic patients with ketoacidosis and after clinical complications]. AB - In 33 insulin-dependent, I and II type diabetic patients the authors evaluated the intraplatelet concentration of 12-hydroperoxyeicozatetraenoic acid (12-HPETE) and malonylodialdehyde (MDA) which are the products of lipoxygenase (LO) and cyclooxygenase (CO) metabolism of arachidonic acid (AA) in blood platelets. Moreover, in all patients, determinations of cholesterol total lipids, phospholipids, triacylglycerols were performed as well as serum lipoproteinogram. The studies were done in diabetic ketoacidosis and 2 weeks after compensation of diabetes was attained. Sixty healthy persons, with no changes in the coagulation system, constituted the control group. In patients with diabetic ketoacidosis a higher intraplatelet concentration of 12-HPETE (7.2 +/- 4.0 nmol/10(9) platelets) was found as compared with the values observed in the control group (4.7 +/- 2.1 nmol MDA/10(9) platelets); p less than 0.01. Intraplatelet MDA concentration did not, however, show a statistically significant difference. When compensation of diabetes was obtained the mean intraplatelet 12-HPETE concentration fell to values close the normal ones (5.5 +/- 3.4 nmol MDA/10(9) platelets). Nevertheless, the results of comparative determinations of mean values of both 12 HPETE and MDA concentrations in ketoacidosis as well as in compensated diabetes did not show statistically significant difference. High intraplatelet 12-HPETE concentration in diabetic ketoacidosis may be a cause of the formation or intensification of atherosclerotic changes, typical of this group of patients. The studies did not prove any correlation between the intraplatelet concentration of AA metabolism products and blood glucose concentration and lipid metabolism products. Neither was there any correlation between 12-HPETE and MDA concentration and the duration of clinically symptomatic diabetes. PMID- 1910165 TI - Intestinal permeability, atopic eczema and oral disodium cromoglycate. AB - A dual sugar (lactulose-mannitol) absorption test was performed in 19 patients with atopic eczema before and after a 21 day elimination-diet. Moreover L/M test was carried out in 20 controls. The mean value of lactulose-mannitol urinary ratio (L/M) was 0.015 (+/- 0.018 SD) in the group of patients and 0.012 (+/- 0.011 SD) in the control group (p = 0.49). The mean clinical score improved significantly after elimination diet (41,6 +/- 12.9 SD before the diet, 21.7 +/- 10.4 SD after the diet, p less than 0.001) but no significant modification of intestinal permeability was recorded (L/M = 0.015 +/- 0.018 SD before the diet and 0.21 +/- 0.022 SD after the diet, p = 0.38). Using a double blind approach we were not able to demonstrate any significant effect of disodium cromoglycate on the clinical score and intestinal permeability. The connections between food allergy, intestinal permeability and atopic dermatitis have not been understood, but disodium cromoglycate doesn't seem to play a significant role in the treatment of atopic dermatitis nor in the modification of intestinal permeability. PMID- 1910166 TI - [Conservative treatment of post-traumatic periduodenal hematoma: presentation of a clinical case and review of the literature]. AB - The authors describe a case of post-traumatic hematoma of the duodenum in a two years old child. This is a very rare condition in paediatric age, but with the increasing incidence of traumatic pathology it can be predicted an increase of this condition. The duodenal hematoma can be treated either with surgical approach or with conservative treatment. The authors discuss the characteristics of the pathology, the etiopathogenetic mechanism, and propose the same classification adopted by some french authors. The type of lesion indicates the adequate therapy; in particular in the case report (type 1) a conservative treatment is adopted. The laboratory parametres are significative but none is diagnostic. In the present case the amylasemia is not elevated until two weeks after the trauma. Very important for diagnosis are T.C., roentgenography and echotomography, the last one can be easily used for the control of the resolution of the hematoma. The conservative treatment is based on nasogastric suction and parenteral nutrition; although the role of nonoperative treatment is emphasized, the importance of careful assessment for signs of peritonitis or enlarging tender mass cannot be overlooked. PMID- 1910168 TI - [Interferons and the substances of growth and differentiation]. PMID- 1910169 TI - Somatic mutation in constant regions of mouse lambda 1 light chains. AB - To study the distribution of somatic mutation, we determined nucleotide sequences of rearranged lambda 1-chain genomic DNA from four hybridomas obtained from C57BL/6 mice that had been immunized with (4-hydroxy-3-nitrophenyl)acetyl conjugated chicken gamma globulin. In total, 114 nucleotide substitutions were observed, with neither insertion nor deletion. Sixty-one mutations occurred in the variable-joining region genes (V lambda 1-J lambda 1) and 49 in joining constant (J lambda 1-C lambda 1) introns. Although frequency decreased with distance from the V lambda 1-J lambda 1 coding region, somatic mutations occurred in the entire J lambda 1-C lambda 1 intron and even in the C lambda 1 region. We found four nucleotide substitutions in C lambda 1 genes, all of which were replacement mutations. Therefore, the mechanism responsible for somatic mutation is operative into the C lambda 1 exons. Nucleotide sequences of rearranged but inactive lambda 2-chain genes from two hybridomas were also examined and compared with those of lambda 1-chain genes. The clustering of replacement mutations in complementarity-determining regions in the inactive lambda 2-chain genes similar to the active lambda 1-chain genes suggested a mechanism that induces somatic mutation preferentially in this region even in the absence of antigenic selection. PMID- 1910170 TI - High-frequency germ-line transmission of plasmid DNA sequences injected into fertilized zebrafish eggs. AB - With the goal of developing techniques for DNA insertional mutagenesis in zebrafish, we established procedures for rapidly obtaining and injecting large numbers of fertilized eggs. Using either of two plasmid constructs, we injected uncut DNA into fertilized eggs at the one- or two-cell stage. Fish hatched from injected eggs were raised to sexual maturity, and the frequency of transgenic founder fish was determined by pair-mating the fish and testing DNA extracted from pools of their 16-hr-old offspring by the polymerase chain reaction (PCR) and then Southern analysis. Eggs injected with one of two different plasmids yielded no transgenic fish, but 7-25% (19 of 115 overall) of the eggs injected with the other plasmid transmitted the injected sequences to their offspring (F1). Of seven lines studied further, all were able to pass the foreign DNA sequences to the next (F2) generation. Inheritance in the F2 generation was Mendelian in the five lines tested. PCR and Southern analysis indicated that the plasmid sequences were present in multiple copies, probably tandemly arranged. Two founder fish carried more than one independent integration of the plasmid sequences. The line studied in more detail was a mosaic carrying two independently segregating copies of the transgene in one germ cell and a third copy in another germ-line precursor cell. The ability to obtain and inject large numbers of zebrafish eggs combined with a high frequency of germ-line integration may be steps toward the goal of being able to perform insertional mutagenesis with this organism. PMID- 1910171 TI - Drosophila has a twitchin/titin-related gene that appears to encode projectin. AB - The sequences of twitchin and titin identify a superfamily of muscle proteins whose functions are not completely understood. In spite of their shared structural features, twitchin and titin appear to differ in function. Genetic and molecular evidence suggests that twitchin has a regulatory role in muscle contraction, whereas it has been proposed that titin has a structural function. We report here that Drosophila has a single-copy gene containing the two-motif amino acid sequence pattern that characterizes twitchin and titin. This gene appears to encode projectin, a muscle protein that is thought to play a structural role in asynchronous flight muscle but may have a role like that of twitchin in synchronous muscle. Thus Drosophila appears to be a case where the apparently diverged functions of twitchin and titin are encoded by a single gene. PMID- 1910176 TI - Enhancement of the cytotoxicity of mistletoe lectin-1 (ML-1) by high pH or perturbation in Golgi functions. AB - We have studied the cytotoxicity of Mistletoe lectin-1 (ML-1), a cytotoxic protein produced by Viscum album, in CHO and V79 cells and in mutant cell lines altered in Golgi functions or in endosomal acidification. In wild-type CHO cells, cytotoxicity of ML-1 was greatly enhanced by ammonium chloride or nigericin. A CHO mutant defective in endosomal acidification (DMPR-2), which is resistant to diphtheria toxin, modeccin and Pseudomonas aeruginosa exotoxin A and hypersensitive to ricin, showed increased sensitivity to ML-1. MonR-31 and MF-1 are monensin- and compactin-resistant mutants derived from CHO and V79 cell lines, respectively, and are presumably altered in Golgi functions. The cytotoxicity of ML-1 was found to be increased in both MonR-31 and MF-1 cells as compared with their parental cells. These results indicate that the effects of chemicals or mutations altering endosomal acidification and Golgi functions on the cytotoxicity of ML-1 are similar to those on ricin cytotoxicity. Our results suggest that the cytotoxicity of ML-1 is enhanced by an increase in endosomal pH, as well as by chemicals or mutations altering the structure/functions of the Golgi regions. Like ricin, the intoxication process of ML-1 may involve the Golgi regions. PMID- 1910178 TI - Studies on the genotoxic properties of essential oils with Bacillus subtilis rec assay and Salmonella/microsome reversion assay. AB - Genotoxic properties of essential oils from Anthemis nobilis L., Artemisia dracunculus L., Salvia officinalis L., Salvia sclarea L., Satureja hortensis L., Satureja montana L., Thymus capitatus L., Thymus citriodorus Schreb., Thymus vulgaris L., Citrus bergamia Risso, were studied with Bacillus subtilis rec-assay and Salmonella/microsome reversion assay. The essential oil of Artemisia dracunculus L. "Piemontese" turned out to be active in the rec-assay but not in the Salmonella test. DNA-damaging activity was demonstrated to be due to the estragol component of the oil. Advantages of the combined use of these two short term microbial assays in genotoxic studies are discussed. PMID- 1910177 TI - Oxygen consumption during sleep in children under continuous and cyclic nutrition. AB - The present study investigated the effects of two modalities of parenteral nutrition (continuous nutrition over the 24-hour period vs. cyclic nutrition, i.e., administered only during the night) on O2 consumption during sleep in children affected by severe gastrointestinal diseases. In both feeding modalities O2 consumption was always highest in REM sleep, intermediate in stage 2 and lowest in SWS. The trends during the night of O2 consumption (an increase from the second to the third part of the night) for different sleep stages were comparable in both feeding modalities. These results suggest that O2 consumption is not affected by the feeding modalities investigated, but is dependent on both sleep stages and time of night. PMID- 1910172 TI - Replication of human immunodeficiency virus type 1 in primary dendritic cell cultures. AB - The ability of the human immunodeficiency virus type 1 (HIV-1) to replicate in primary blood dendritic cells was investigated. Dendritic cells compose less than 1% of the circulating leukocytes and are nondividing cells. Highly purified preparations of dendritic cells were obtained using recent advances in cell fractionation. The results of these experiments show that dendritic cells, in contrast to monocytes and T cells, support the active replication of all strains of HIV-1 tested, including T-cell tropic and monocyte/macrophage tropic isolates. The dendritic cell cultures supported much more virus production than did cultures of primary unseparated T cells, CD4+ T cells, and adherent as well as nonadherent monocytes. Replication of HIV-1 in dendritic cells produces no noticeable cytopathic effect nor does it decrease total cell number. The ability of the nonreplicating dendritic cells to support high levels of replication of HIV-1 suggests that this antigen-presenting cell population, which is also capable of supporting clonal T-cell growth, may play a central role in HIV pathogenesis, serving as a source of continued infection of CD4+ T cells and as a reservoir of virus infection. PMID- 1910173 TI - Molecular dynamics of dopamine at the D2 receptor. AB - A three-dimensional model of the dopamine D2 receptor, assumed to be a target of antipsychotic drug action, was constructed from its amino acid sequence. The model was based on structural similarities within the super-family of guanine nucleotide-binding regulatory (G) protein-coupled neuroreceptors and has seven alpha-helical transmembrane segments that form a central core with a putative ligand-binding site. The space between two residues postulated to be involved in agonist binding, Asp-80 and Asn-390, perfectly accommodated an anti-dopamine molecule. Molecular electrostatic potentials were mainly negative on the synaptic side of the receptor model and around aspartate residues lining the central core and positive in the cytoplasmic domains. The docking of dopamine into a postulated binding site was examined by molecular dynamics simulation. The protonated amino group became oriented toward negatively charged aspartate residues in helix 2 and helix 3, whereas the dopamine molecule fluctuated rapidly between different anti and gauche conformations during the simulation. The receptor model suggests that protonated ligands are attracted to the binding site by electrostatic forces and that protonated agonists may induce conformational changes in the receptor, leading to G-protein activation, by increasing the electrostatic potentials near Asp-80. PMID- 1910175 TI - Virus-triggered acquired immunodeficiency by cytotoxic T-cell-dependent destruction of antigen-presenting cells and lymph follicle structure. AB - Virus-induced acquired immune suppression in mice infected with lymphocytic choriomeningitis virus is shown here to be caused by the CD8+-T-cell-dependent elimination of macrophages/antigen-presenting cells. Surprisingly, this is associated with severe destruction of the follicular organization of lymphoid organs, indicating a crucial role for dendritic cells and marginal zone macrophages in maintaining follicular structure. Once established, this immunopathology cannot be readily reversed by the elimination of CD8+ effector cells. Such a T-cell-mediated pathogenesis may play a pivotal role in acquired virus-induced immunosuppression and may represent one strategy by which virus escapes immune surveillance and establishes persistent infections in initially immunocompetent hosts. PMID- 1910179 TI - Today's challenges to the Public Health Service and to the nation. PMID- 1910186 TI - Requiring formal training in preventive health practices for child day care providers. AB - The study was a test of the feasibility of mandating training in preventive health practices for child day care providers in California. Three approaches were taken to determining the feasibility of mandatory training. They were (a) to identify persons and groups with the capability to provide training, (b) to identify systems and networks for communication and collaboration on health issues related to day care at the local level, and (c) to determine the child day care providers' concerns, needs, and future interests regarding child health. Information was collected on relevant courses offered by universities, colleges, and adult education programs; on training offered by child health authorities; and on formal curriculums offered by local and national sources. Day care center and family day care home providers were surveyed to determine their knowledge of child health issues, their concerns, and their future needs. The providers surveyed cared for a total of 14,340 children. Information on local networks was obtained from the surveys, from interviews, and from a special task force that had been set up to advise the State legislature. Study results supported the conclusion that a coordinated system of State-wide training was feasible, given the existing networks of training and educational resources, the number of day care providers who had already been motivated to seek some training in child health practices, and the almost unanimous interest among day care providers in obtaining training. Mandating training in child health for day care providers will require a commitment in the form of new legislation outlining basic requirements and allocating funding. The implementation and costs of such a mandate at the State and local level are discussed. PMID- 1910180 TI - Reducing infant mortality in the United States through "Healthy Start". PMID- 1910181 TI - A comprehensive local program for the prevention of fetal alcohol syndrome. AB - A hospital based, comprehensive approach to the prevention of Fetal Alcohol Syndrome and Fetal Alcohol Effects that combines clinical assessment, community outreach, and epidemiologic knowledge to attack alcohol-related birth defects is described. The program includes training of clinicians and members of the community, baseline screening of suspected children, and alcohol consumption screening of pregnant women in prenatal clinics. The major, although not exclusive, focus of the program is on tertiary prevention undertaken with women defined as "high risk" for producing alcohol affected children. Of the 48 women referred to the program at the Tuba City, AZ, Indian Medical Center between January 1988 and July 1989, 39 (81 percent) became participants. Complete followup was possible on 31; 17 of them reported alcohol abstinence in July 1989, 18 months into the program. Of the 29 referred women who were pregnant at the time, 21 agreed to participate; of these, 19 (85.7 percent) were abstinent by the third trimester of pregnancy; 5 voluntarily accepted offers of contraceptive measures after the birth of their child. PMID- 1910185 TI - A survey of newspaper coverage of HCFA hospital mortality data. AB - A study that assessed newspaper coverage of the 1986 Hospital Mortality Data for Medicare Patients released by the Health Care Financing Administration (HCFA) of the U.S. Department of Health and Human Services is described. Media interpretation of Federal information about the quality of hospital medical care is also discussed. A sample of 68 articles from newspapers serving urban areas of various sizes in all regions of the United States was analyzed. Articles were coded into classifications according to how the news was played, headline bias (positive-negative-neutral), hospital mentions, quote sources, explanations for excessively high mortality rates, urban area population, and geographic region. The findings indicated that HCFA's release of the 1986 hospital mortality data received heavy news coverage. There were twice as many negative headlines as positive ones, although nearly 95 percent of the hospitals had mortality rates within expected ranges. Quotes from representatives of hospitals predominated in the newspaper articles, and they often blamed some aspect of the HCFA data for higher-than-expected mortality rates. Newspaper attention to the quality of hospital care clearly raised consumer awareness of the idea that health care quality can vary. The newspaper articles, however, provided no guidance on obtaining valid data or on using it to make health care choices. PMID- 1910183 TI - A racial and ethnic comparison of family formation and contraceptive practices among low-income women. AB - Low-income women's histories of pregnancies, their use or nonuse of contraception, and their marital status showed racial and ethnic differences in family formation patterns and fertility control practices. Data were analyzed from a survey of 918 low-income women in Los Angeles County. The sample contained about equal numbers of non-Hispanic whites, blacks, and Hispanics. The use of stratified samples equalized the poverty-level composition of the three racial and ethnic groups. First pregnancies for white and black women resulted primarily from nonuse of contraception while unmarried, but almost half of first pregnancies among Hispanics were intentional. Marital dissolution following pregnancy or childbearing was common among low-income whites and blacks, but Hispanics were more likely to have an intact marriage along with a higher average parity. Analyses of histories of pregnancies while controlling for demographic characteristics showed that racial and ethnic differences in rates of different types of pregnancies (classified as intended, accidental, or unprotected) and rates of abortion did not remain significant after adjustment for respondent characteristics and years of exposure to possible pregnancy. Actual parity, however, remained significant when these factors were controlled. Thus, results document distinctive patterns of family formation for low-income women in racial and ethnic subgroups of this population. Implications of these patterns of family formation for economic well-being are discussed. PMID- 1910182 TI - Prevalence of Chlamydia trachomatis infection in pregnant patients. AB - Chlamydia is a sexually transmitted disease of epidemic proportions, infecting an estimated 4 million people a year. It results not only in infertility and ectopic pregnancy but also in infant morbidity and mortality. Ectopic pregnancy is responsible for 11 percent of maternal deaths. About 60 percent of infected women can transmit the bacteria at birth to their infants. Early detection and treatment of chlamydia in both men and women, especially prenatal women, is critical. Chlamydia trachomatis infection of the cervix was found in 8.1 percent of a group of 1,004 pregnant women at a hospital prenatal clinic by means of a direct fluorescent antibody test. The prevalence of C. trachomatis was only 0.7 percent in 277 pregnant women receiving prenatal care from private practitioners. All patients between 27 and 30 weeks gestation who tested positive were treated with oral erythromycin. Their partners were treated with tetracycline. The outcome of pregnancy in patients treated for chlamydial infection was compared with a control group of noninfected mothers from the same population. The frequency of premature rupture of the membranes, prematurity, and low Apgar scores among the treated women were not significantly different from those in the control group. There was a significant difference, however, between the two groups in the incidence of low mean birth weight infants and the presence of meconium. Children can acquire a chlamydial infection at birth from contact with infected cervico-vaginal secretions. If not detected and treated, these infected infants may develop conjunctivitis, bronchiolitis, and pneumonia. It is suggested, therefore, that all patients at prenatal clinics be screened for chlamydial cervicitis. Those testing positive and their partners should be treated. PMID- 1910187 TI - Evaluating South Carolina's community cardiovascular disease prevention project. AB - A community cardiovascular disease prevention program was undertaken as a cooperative effort of the South Carolina Department of Health and Environmental Control and the Centers for Disease Control of the Public Health Service. As part of the evaluation of the project, a large scale community health survey was conducted by the State and Federal agencies. The successful design and implementation of the survey, which included telephone and in-home interviews as well as clinical assessments of participants, is described. Interview response rates were adequate, although physical assessments were completed on only 61 percent of those interviewed. Households without telephones were difficult and costly to identify, and young adults were difficult to locate for survey participation. The survey produced baseline data for program planning and for measuring the success of ongoing intervention efforts. Survey data also have been used to estimate the prevalence of selected cardiovascular disease risk factors. PMID- 1910189 TI - WIC program participation--a marketing approach. AB - Recent evaluation studies have described the benefits accruing to low-income women and children who participate in the Special Supplemental Food Program for Women, Infants, and Children (WIC). However, participation is not uniform among all groups of eligible persons. This study examines the geographic variation in WIC participation rates of eligible pregnant women in Rhode Island to determine whether the program is effective in reaching the neediest segments of the population. Eight groups of small geographic areas in Rhode Island (census tracts) were formed on the basis of need for maternal and child health services, as determined from a statistical method employing factor and cluster analysis of existing health and sociodemographic data. Among these eight groups, participation rates in WIC during 1983-84 ranged from 46 percent to more than 100 percent of estimated eligible pregnant women. The rates were positively correlated with measures of need, strongly (r = 0.92) with an index of maternal risk, and less strongly (r = 0.79) with an index of birth outcomes. The results of this study have enabled the Rhode Island WIC Program to direct its outreach efforts more specifically to geographic areas where the need for the program's assistance is greatest. The procedures described in this report comprise a technique that can be generally applied to measure program effectiveness in marketing and outreach where relevant data are available by small geographic areas. The data requirements are (a) population-based estimates of program need and (b) program utilization measures. If these data can be aggregated to a common set of small geographic areas, the use of marketing analysis techniques becomes possible, and program benefits in the area of outreach and recruitment can be realized. PMID- 1910188 TI - Association between exercise and other preventive health behaviors among diabetics. AB - Two hundred and seventy patients were studied to investigate the cross sectional association between exercise and other preventive health behaviors in a diabetic population. Patients included both insulin and noninsulin dependent diabetics and were recruited from the Family Practice and Pediatrics Clinics at Bowman Gray School of Medicine. During screening, patients underwent a physical examination as well as completing a survey to assess exercise and health behavior habits. Three exercise groups were compared: (a) patients who expended more than 600 kilocalories per week during exercise, (b) patients who expended 600 kilocalories or less, and (c) patients who did not exercise. The mean body weights of both exercise groups were found to be less than the nonexercise group, and the heavy exercise group also had a lower mean body mass index. Heavy exercisers reported greater caloric intakes than both moderate and nonexercisers. There were no differences found concerning the composition of their diets among groups. The heavy exercise group reported wearing their seatbelts a greater percentage of the time and visited the dentist more often compared with the sedentary group. There were no significant differences found among exercise groups concerning blood sugar monitoring, alcohol consumption, smoking, or in obtaining periodic health examinations. It was concluded that exercise was associated with several, but not a majority, of other healthful behaviors in a population of diabetics. PMID- 1910174 TI - Identification of Dictyostelium G alpha genes expressed during multicellular development. AB - Guanine nucleotide-binding protein (G protein)-mediated signal transduction constitutes a common mechanism by which cells receive and respond to a diverse set of environmental signals. Many of the signals involved in the developmental life cycle of the slime mold Dictyostelium have been postulated to be transduced by such pathways and, in some cases, these pathways have been demonstrated to be dependent on specific G proteins. Using the polymerase chain reaction, we have identified two additional Dictyostelium G alpha genes, G alpha 4 and G alpha 5, that are developmentally regulated. Transcripts from both of these genes are primarily expressed during the multicellular stages of development, suggesting possible roles in cell differentiation or morphogenesis. The entire G alpha 4 gene was sequenced and found to encode a protein consisting of 345 amino acids. The G alpha 4 subunit is homologous to other previously identified G alpha subunits, including the Dictyostelium G alpha 1 (43% identity) and G alpha 2 (41% identity) subunits. However, the G alpha 4 subunit contains some unusual sequence divergences in residues highly conserved among most eukaryotic G alpha subunits, suggesting that G alpha 4 may be a member of another class of G alpha subunits. PMID- 1910192 TI - Tobacco advertising in retail stores. AB - Recent studies have described tobacco advertising in the print media, on billboards, and through sponsorship of cultural and sporting events. However, little attention has been given to another common and unavoidable source of tobacco advertising, that which is encountered in retail stores. In July 1987, we conducted a survey of 61 packaged goods retail stores in Buffalo, NY, to assess the prevalence and type of point-of-sale tobacco advertising. In addition, store owners or managers were surveyed to determine their store's policy regarding tobacco advertising, receipt of monetary incentives from distributors for displaying tobacco ads, and willingness to display antitobacco ads. Six types of stores were involved in the study: 10 supermarkets, 10 privately owned grocery stores, 9 chain convenience food stores that do not sell gasoline, 11 chain convenience food stores that sell gasoline, 11 chain pharmacies, and 10 private pharmacies. Two-thirds of the stores displayed tobacco posters, and 87 percent had promotional items advertising tobacco products, primarily cigarettes. Larger stores, and those that were privately owned, tended to display more posters and promotional items. Eighty percent of tobacco product displays were for cigarettes, 16 percent for smokeless tobacco products, and 4 percent for cigars and pipe tobacco. Convenience stores selling gasoline had the most separate tobacco product displays. Of tobacco product displays, 24 percent were located adjacent to candy and snack displays. Twenty-nine of the 61 store owners or managers indicated that their store had a policy regulating the display of tobacco ads and tobacco product displays. Policies dealt primarily with the location of tobacco posters (for example, no ads in the window) and number of product displays. Only 14 shop owners or managers indicated that they had previously displayed antitobacco information; more than half (31 of 61) said that they would be willing to display antitobaccoads.In many stores space availability is a barrier to displaying antitobacco information. Materials should be designed that have some utility for the store, such as posters that list store hours or directional information (that is, in and out signs).Antitobacco messages could also be displayed on check out dividers, check out mats, shopping carts,shopping bags, and milk cartons. In chain stores,decisions regarding the display of antitobacco information are likely to be made at the corporate level. Standards encouraging retailers to adopt more responsible policies related to advertising and sale of tobacco products should be established. PMID- 1910190 TI - Minerals in hair, serum, and urine of healthy and anemic black children. AB - Hair mineral analysis can be used as a reliable screening test for heavy metals, but it is not an established method for defining nutritional and disease states. Wide variation in test results is a major problem in utilizing the technique for clinical purposes. Better reference values are needed, especially for children, as well as information about how hair mineral values correlate with body fluid values. A total of 48 black children were studied. Of these, 20 were normal children, ages 1 to 17; 12 were normal infants, ages 5 weeks to 12 months; 3 were children with iron overload; 7 had iron deficiency anemia; and 6 had thalassemia trait. There were in all 17 boys and 31 girls. The distribution of 15 minerals in hair, serum, and urine samples was determined by energy dispersive X-ray fluorescence. Mineral concentrations from the normal children were compared with concentrations obtained from the children with iron overload, iron deficiency anemia, and thalassemia trait. Statistical analysis revealed no significant differences among any of the groups. Mineral concentrations from the normal infants and children may be useful as reference values. The analysis of hair iron as a valid screening test for body iron status in children is not supported by our data. PMID- 1910193 TI - Motorcycle helmet use in Texas. AB - Helmets worn by motorcyclists decrease head injuries and the likelihood of being killed in a crash by about 30 percent. From 1968 to 1977, Texas had a comprehensive motorcycle helmet use law, which was estimated to have saved 650 lives. But the law was amended in 1977 to apply only to motorcycle operators and passengers under age 18. In September 1989, a new law was passed that required helmets for all motorcycle operators and passengers. Observations of helmet use were conducted before and after the law took effect in 18 Texas cities using a survey design providing a cross-section of urban and suburban traffic across the State. The surveys indicated that helmet use increased from less than 50 percent just before the law to 90 percent immediately after, and it increased further to more than 95 percent 2 months later. These results confirm the unique effectiveness of comprehensive helmet use laws in applying the proven public health benefits of helmets to the reduction of motorcycle injuries and deaths. PMID- 1910191 TI - Evaluation of "Guia para Dejar de Fumar," a self-help guide in Spanish to quit smoking. AB - Because of the absence of culturally appropriate self-help smoking cessation materials for Latinos, a new Spanish language cessation guide, "Guia para Dejar de Fumar," was developed and evaluated. It was distributed as part of a community wide intervention to decrease the prevalence of smoking. The "Guia" is an attractive full-color booklet written in universal Spanish that uses simple text and numerous photographs. Motivation to quit smoking is emphasized, and graphic demonstrations of the adverse health effects of smoking are included. A menu of quitting and maintenance techniques is presented. A total of 431 smokers were identified for evaluation at approximately 3, 6, and 12 months after receiving the "Guia." Self-reported quit rates declined from 21.1 percent at 2.5 months to 13.7 percent at 14 months; 8.4 percent of the sample had a validated quit status by saliva cotinine test at 1 year. Persons older than 44 years were more likely to remain nonsmokers, but sex, education, acculturation score, and cigarettes smoked per day did not predict smoking cessation. The components of the "Guia" most mentioned by those who were surveyed were the graphic photographs, the health emphasis, and the overall format. The authors concluded that the "Guia" is an appropriate self-help smoking cessation booklet for Spanish-speaking Latinos in the United States. PMID- 1910194 TI - Reporting of communicable diseases by university physicians. AB - Billing records from the outpatient clinics of the University of Arizona were compared to case reports of communicable diseases received by the local health department. Of 286 cases of reportable diseases found, 183 (64 percent) were reported to the local health department. Sexually transmitted diseases were more likely to be reported than other diseases [risk ratio (RR) = 1.97; 95 percent confidence interval (CI), 1.62-2.39]. Diseases of residents of Pima County were more likely to be reported than those of residents of other Arizona counties (RR = 1.40; 95 percent CI, 1.11-1.77), and diseases in Arizona residents were more likely to be reported than those of residents of other States (RR = 2.37; 95 percent CI, 1.35-4.15). Diseases of citizens of other countries were never reported. The only significant difference found among the specialty clinics of the medical center was that pediatricians reported less frequently than others (RR = 0.75; 95 percent CI, 0.58-0.98). PMID- 1910195 TI - Staff patterns of epidemiologists in the health departments of 12 southern states. AB - In November 1989, representatives from 12 States attending the Annual Convocation of Southern State Epidemiologists completed a survey to enumerate epidemiologists working in central offices of State health departments. Epidemiologists were classified according to education and program area. A total of 117 epidemiologists were identified, yielding a range among the States of 0.6 to 8.3 (median 1.9) epidemiologists per million population. The most common degree was a medical degree, followed by master's training in epidemiology or biostatistics; only 9 percent had doctoral training in epidemiology or biostatistics. More than one-third of the epidemiologists worked in infectious diseases, including acquired immunodeficiency syndrome (AIDS) and sexually transmitted diseases, and about one-fifth worked in environmental epidemiology. The areas of injuries, cancer, chronic diseases, maternal and child health, and occupational health collectively accounted for about one-fifth of epidemiologists. The results of the survey suggest room for further epidemiologic training among health department epidemiologists. The results also identify areas where additional epidemiologic input would be beneficial. PMID- 1910197 TI - Most physicians and nurses favor mandatory AIDS tests. PMID- 1910199 TI - Effect of aflatoxin B1 on the efficacy of turkey herpesvirus vaccine against Marek's disease. AB - The effect of feeding aflatoxin B1 (AFB1) (0.5 ppm) was studied in young chicks. The frequency and the severity of gross and microscopic lesions of Marek's disease were significantly higher in those birds which had been vaccinated with turkey herpesvirus (HVI) and birds challenged with Marek's disease virus which had been given AFB1 in the feed than in those given normal feed. The protective efficacy of HVT vaccine, as judged on the basis of gross and histopathological lesions, was 86.1 and 77.3 per cent in normally fed birds in comparison to 37.6 and 8 per cent in AFB1 fed birds. PMID- 1910196 TI - Drug use and sexual behavior of indigent African American men. AB - A total of 108 African American men in a free lunch program with histories of drug abuse were surveyed to determine the relationships among drug use, sexual activity, AIDS prevention practices, and perceived risk of AIDS. Of the 108, 69.5 percent were homeless and only 12 percent were currently receiving drug abuse treatment. More than half of the participants had injected drugs, and 38 percent had shared needles. Among the 80 percent who were sexually active, 40 percent reported using condoms every time they had sex. Respondents in monogamous relationships tended to use condoms less frequently. Those who shared needles were more likely to have sex with IV drug users and had more sexual partners. Respondents who used crack used condoms less frequently. Those with multiple partners were more likely to engage in anal intercourse. Three-quarters perceived themselves at risk of AIDS. PMID- 1910201 TI - Differential sugar absorption for the assessment of canine intestinal permeability: the cellobiose/mannitol test in gluten-sensitive enteropathy of Irish setters. AB - Intestinal permeability was assessed in Irish setters with gluten-sensitive enteropathy by oral administration of an isotonic solution of cellobiose and mannitol, and measurement of their urinary excretion ratio. The cellobiose/mannitol ratio was increased in affected Irish setters fed a wheat containing diet compared both with littermates reared on a cereal-free diet, with no evidence of jejunal damage, and clinically healthy Irish setters. The ratio fell following six weeks on a gluten-free diet to be comparable with control values, and subsequently increased after six weeks gluten challenge. The results indicate that the cellobiose/mannitol test may be useful for the detection of mucosal damage and for monitoring the response to therapy. PMID- 1910198 TI - Organization and structure of wild rabbit kappa2 genes: implications for regulation of kappa expression. AB - In domestic populations, the rabbit kappa light chains are known to be encoded by two loci which are unequally expressed. The kappa1 chains account for the majority of total serum kappa chains, and display an unusual complex polymorphism. In order to study the evolution and the putative correlations between the expression, the organization and the structure of the kappa genes, we analysed the kappa loci in wild rabbit populations. The kappa genes of b95, b97 and b98 allotypes are organized in two loci similar to that of domestic rabbits. The structure of the constant region of the kappa2 locus was determined from a wild rabbit which expresses b95 allotype kappa1 chains. The Ckappa2bas2 of b95 displays a single silent mutation when compared to Ckappa2bas2 associated with b4 and one amino acid change relative to Ckappa2bas1 chain. Therefore, in contrast to the kappa1 locus, the constant regions of the kappa2 locus display strong conservation during evolution. A model based on conformation of the kappa chains is discussed to explain the evolution and expression of the two kappa loci. PMID- 1910205 TI - Ancient DNA: still busy after death. PMID- 1910204 TI - Regulation of PCBs. PMID- 1910200 TI - Analgesic activity and respiratory effects of butorphanol in sheep. AB - The analgesic drug butorphanol tartrate has proved useful clinically in horses and dogs but its analgesic profile had not yet been investigated in sheep. This study was initiated to determine the thermal and mechanical antinociceptive activity of butorphanol (at the dose rates 0.05, 0.1 and 0.2 mg kg-1) in sheep. The drug produced significant analgesia in the thermal test system, the duration of which was dose related but no significant elevation in mechanical pressure thresholds could be detected. In a further set of experiments the dose rate was increased to 0.4 mg kg-1 and mechanical testing was repeated. There was still no clinically significant elevation in pressure thresholds. At a dose rate of 0.2 mg kg-1 the drug had no detectable effect on respiratory blood gas tensions. Behavioural changes were severe if a dose rate of 0.2 mg kg-1 was exceeded. PMID- 1910202 TI - Post natal ontogeny of immunological responsiveness in Merino sheep. AB - Sheep in five age groups (two weeks, 10 weeks, 18 weeks, six months and four years old) were immunised systemically, twice, with ovalbumin or Brucella abortus (live or killed) and antibody responses in blood were measured. The animals were also infected with the nematode parasites Trichostrongylus colubriformis and Haemonchus contortus and faecal egg counts and serum antibody responses to larval antigens were measured. The experiments were designed so that, as far as possible, the effect of age per se could be dissociated from the combined effects of age and prior exposure to antigen. The effects of the age of sheep were more marked for antibody responses to Brucella abortus lipopolysaccharide than to ovalbumin. Older animals had much greater resistance to infection with internal parasites, as shown by the magnitude of the faecal egg count. In contrast to older lambs, neonatal lambs (infected with H contortus at two weeks old) had consistently declining concentrations of anti-H contortus antibody in their serum, mounted no detectable autogenous anti-H contortus antibody response in blood and appeared to develop no resistance to the parasite. Post natal ontogeny of immune responses was different for the various antigens/pathogens. PMID- 1910203 TI - [A case of acute myocardial infarction due to coronary spasm]. AB - The patient was a 47 year-old man, who has been known to have effort angina since September 1989. His exercise stress ECG has revealed ST elevation in V2-V4 with maximum exercise. He experienced severe chest pain lasting for an hour on the way to his office in the early morning on November 16, 1989, and was admitted to our hospital. His ECG and laboratory findings indicated typical acute anteroseptal myocardial infarction, but the coronary arteriography (CAG) which was performed 7 hours after the onset showed no significant stenotic lesion. After administrating nitrate and calcium antagonist, he has had no attack of angina pectoris and his exercise stress test has revealed no ST-T changes on his ECG. 1 month later, while antianginal drugs were discontinued in order to perform an ergonovine stress test, the patient frequently complained of left anterior chest pain with remarkable ST elevation in precordial leads on his ECG. The CAG at chronic stage revealed that there was a 99% stenosis at Segment 6 of the left anterior descending artery (LAD) which was supplied with good collateral flow from the right coronary artery. The LAD was completely occluded at Segment 6 after intracoronary administration of ergonovine maleate 0.005 mg to the left coronary artery. After the intracoronary infusion of isosorbide dinitrate, there was no significant stenosis seen in the LAD except the minimum wall irregularity at Segment 6. These findings suggested that coronary spasm might play a major role of the occurrence of acute myocardial infarction in this case.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1910207 TI - Depletion of CD4+ T cells in major histocompatibility complex class II-deficient mice. AB - The maturation of T cells in the thymus is dependent on the expression of major histocompatibility complex (MHC) molecules. By disruption of the MHC class II Ab beta gene in embryonic stem cells, mice were generated that lack cell surface expression of class II molecules. These MHC class II-deficient mice were depleted of mature CD4+ T cells and were deficient in cell-mediated immune responses. These results provide genetic evidence that class II molecules are required for the maturation and function of mature CD4+ T cells. PMID- 1910184 TI - Preventing secondary infections among HIV-positive persons. AB - Secondary infectious diseases contribute substantially to morbidity and mortality of people infected with human immunodeficiency virus (HIV). The authors developed comprehensive, practical recommendations for prevention of infectious complications in HIV-infected people. Recommendations are concerned with the pathogens that are more common or more severe in HIV-infected people. Several infectious complications can be prevented by avoiding ingestion of contaminated food or water. Zoonoses can be prevented by precautions to be taken in contacts with animals. The risk of several fungal diseases can be reduced if activities likely to lead to inhalation of spores are avoided. HIV-infected people should be advised how to lower adverse health effects of travel, especially international travel. The potential for infectious complications of sexual activity and illicit drug use should be stressed, and recommendations to reduce the risk are discussed. Recommendations for use of vaccines in HIV-infected people are reviewed. Blood CD4+ lymphocyte concentrations, tuberculin skin testing, Toxoplasma serology, and sexually transmitted disease screening should be performed in certain subsets of HIV-infected people. Guidelines for chemoprophylaxis against Pneumocystis carinii and tuberculosis are presented. Recent data suggest that intravenous immunoglobulin therapy may prevent bacterial infections in HIV-infected children. PMID- 1910210 TI - Development of diagnostic data in the 10-percent sample of disabled SSI recipients. AB - The Social Security Administration has created a 10-percent sample data base of blind and disabled recipients from the Supplemental Security Income (SSI) program. Codes showing the primary medical diagnosis were obtained for the sample by matching several files, and by imputing codes to sample cases where no diagnostic codes were found. The data base is updated each year by repeating this matching operation and by bringing forward the diagnostic codes from the previous year's file. This article describes the sources of diagnostic information in the administrative record system; the methodology used in the development of the 10 percent disability data base, and the technique chosen to compensate for missing values. PMID- 1910214 TI - Laboratory and clinical features in systemic lupus erythematosus patients with or without anticardiolipin antibodies. AB - The purpose of this study was to investigate whether the presence of anticardiolipin antibodies (aCL) in systemic lupus erythematosus (SLE) patients was associated with particular laboratory or clinical features. Anticardiolipin antibodies were determined in 63 unselected SLE patients: 32 (50.8%) were found to be aCL positive and this positivity was significantly associated with the presence of lupus anticoagulant (p less than 0.003) and false positive VDRL reaction (p less than 0.001), but not with other haematological or biological markers. Thrombin-antithrombin III (TAT) complexes were found to be increased with disease activity, but no relationship was found between TAT complexes and the presence or absence of aCL. In this study a statistically significant association was found between aCL positivity and arterial thromboembolic events, but not with venous thrombotic complications. In summary half of SLE patients had aCL and the presence of these antibodies was associated with other antiphospholipid antibodies and with arterial thromboembolic events. PMID- 1910212 TI - Regional fibrinolysis following total hip replacement. AB - The local effect of operative trauma on the fibrinolytic system was studied in ten patients undergoing total hip replacement. Catheters were inserted in the femoral veins on both sides and blood was sampled from these catheters perioperatively. The following fibrinolytic variables were analysed in plasma and related to the different steps of surgery: tissue plasminogen activator (t-PA) activity, t-PA antigen and plasminogen activator inhibitor (PAI-1) activity. During surgery PAI-1 activity and t-PA antigen in the operated limb were significantly increased compared with preoperative values. There was a significant difference in PAI-1 activity and t-PA antigen between the operated and the non-operated limbs during surgery and within one hour postoperatively. During fixation of the femoral implant there was a significant difference between the operated and the non-operated limbs in t-PA activity. Thus the regional fibrinolytic response to trauma was dissociated from the response in the non operated limb. The clinical relevance of the observed alterations in regional fibrinolysis, as related to thrombogenic mechanisms after hip surgery, remains to be elucidated. PMID- 1910208 TI - Homo sapiens' reproductive drive. PMID- 1910211 TI - Changes in plasmatic tissue-type plasminogen activator and plasminogen activator inhibitor activity during acute arterial occlusion associated with severe ischemia. AB - Severe lower limb ischemia in patients with acute arterial occlusion was associated with a significant increase in systemic fibrinolytic activity. Plasmatic level of t-PA activity was twice the normal value at the peak of ischemia. This level declined gradually within no less than 40 hours after reperfusion procedure or limb amputation had reverted the ischemic state. In spite of major tissue damage and surgical trauma, plasmatic PAI activity stayed within normal range, and did not increase within the first 24 hours postoperatively. These findings strongly suggest that acute ischemia initiates systemic induction of excessive and continuous release of t-PA, which outweighs any anticipated increase in PAI activity. PMID- 1910206 TI - Atomic force microscopy and dissection of gap junctions. AB - An atomic force microscope (AFM) was used to study the structure of isolated hepatic gap junctions in phosphate-buffered saline (PBS). The thickness of these gap junctions appears to be 14.4 nanometers, close to the dimensions reported by electron microscopy (EM). When an increasing force is applied to the microscope tip, the top membrane of the gap junction can be "dissected" away, leaving the extracellular domains of the bottom membrane exposed. When such "force dissection" is performed on samples both trypsinized and fixed with glutaraldehyde, the hexagonal array of gap junction hemichannels is revealed, with a center-to-center spacing of 9.1 nanometers. PMID- 1910215 TI - Lipopolysaccharide induces double-stranded DNA fragmentation in mouse thymus: protective effect of zinc pretreatment. AB - Intraperitoneal injection of female NAW/W1 mice with 5 mg of Salmonella typhimurium lipopolysaccharide/kg results in decreased body and thymus weight. Reduced thymic weight is accompanied by fragmentation of DNA into multimers of about 200 bp size. This effect is consistent with the induction of intranucleosomal cleavage of double-stranded DNA in thymus. Maximal fragmentation of DNA occurs between 18 and 24 h after treatment; by 48 h post lipopolysaccharide treatment, there is little evidence of thymic DNA fragmentation. Pretreatment of mice with Zn protects against lipopolysaccharide induced DNA fragmentation. This effect is maximal at about 72 h after Zn treatment (24 h after lipopolysaccharide treatment) and persists until about 96 h after Zn treatment. At 72 h after pretreatment, the antagonism of thymic DNA fragmentation by Zn is dose-dependent. To examine the role of the acute phase inflammatory response elicited by lipopolysaccharide treatment in the production of changes in thymic weight and DNA integrity, the effects of treatment with casein, a well-characterized inducer of the acute phase inflammatory response in mice, were examined. In contrast to the effect of lipopolysaccharide, casein treatment did not produce a similar pattern of DNA fragmentation in thymus. Taken together, these data suggest that lipopolysaccharide induces DNA fragmentation in thymus by a mechanism which does not occur during the pathophysiological changes which accompany the casein-induced acute phase response. Further, the antagonism by Zn of lipopolysaccharide-induced fragmentation of thymic DNA is consistent with earlier findings that Zn can prevent dexamethasone-induced DNA fragmentation in vitro. PMID- 1910213 TI - Hepatic synthesis and clearance of components of the fibrinolytic system in healthy volunteers and in patients with different stages of liver cirrhosis. AB - We determined plasma levels of tissue-type plasminogen activator (t-PA) antigen, urokinase-type plasminogen activator (u-PA) antigen, and activity of the fast acting inhibitor of plasminogen activator (PAI-1) in patients with different stages of liver cirrhosis (Child A, B, and C) and in age and sex-matched healthy controls to investigate the contribution of the liver to the metabolism of these main components of the fibrinolytic system. For control purposes routine clotting parameters were also determined. In patients with the most severe form of liver cirrhosis (Child C) t-PA antigen levels were significantly elevated as compared to patients with Child A or Child B (p less than 0.05) or to controls (p less than 0.01). Furthermore, Child C patients exhibited significantly decreased PAI-1 plasma levels (p less than 0.05) as compared to controls. We were not able to demonstrate, however, any significant correlation between liver function and u-PA plasma levels. Furthermore, t-PA antigen and albumin plasma levels were negatively correlated (r = 0.48; p = 0.0015) and t-PA antigen and bilirubin were positively correlated (r = 0.46; p = 0.0022) thus indicating that the liver is mainly involved in the clearance of t-PA antigen. PAI-1 activity, however, seems to depend partially on synthesis by the liver as demonstrated by a positive correlation between PAI-1 and albumin (r = 0.33; p = 0.037). These physiologic liver functions are both progressively attenuated in severe liver damage and an increase of t-PA plasma levels and a decrease of PAI-1 might contribute to the higher fibrinolytic tendency observed in those patients. PMID- 1910216 TI - Mouse strain differences in glutathione S-transferase activity and aflatoxin B1 biotransformation. AB - Previous studies have suggested that mice are resistant to the carcinogenic effects of aflatoxin B1 (AFB1) and that this resistance is largely the result of expression of an isoenzyme of glutathione S-transferase (GST) with high activity toward AFB1-8,9-epoxide. Significant interstrain differences in cytosolic GST activities toward a variety of substrates have been reported in mice. If such differences exist for the conjugation of AFB1-8,9-epoxide, then there may be significant mouse strain differences in susceptibility to AFB1-induced hepatocarcinogenicity. The hepatic microsomal and cytosolic biotransformation of AFB1 was studied in 8 different strains of mice fed a purified diet. GST-mediated conjugation of AFB1-8,9-epoxide with glutathione and GST activity toward 1-chloro 2,4-dinitrobenzene (CDNB), 1,2-dichloro-4-nitrobenzene (DCNB), ethacrynic acid (ECA) and cumene hydroperoxide (CHP) were determined with cytosolic fractions from 8-10 pooled livers. Specific activities of cytochrome-P-450-mediated oxidation of AFB1 to aflatoxin Q1 (AFQ1), aflatoxin M1 (AFM1), and aflatoxin P1 (AFP1), as well as the reactive intermediate AFB1-8,9-epoxide, were determined with hepatic microsomal fractions from each mouse strain. No striking differences in specific activity between mouse strains were observed for any of the P-450- or GST-mediated enzymatic pathways measured, although some statistically significant differences were found. GST specific activities toward AFB1-8,9-epoxide, CDNB, DCNB, ECA and CHP ranged from 1.5-2.1, 2,830-5,370, 81-144, 38-69 and 32-73 nmol/mg protein/min, respectively. The rate of formation of AFB1-8,9-epoxide ranged from 208 to 465 pmol/mg protein/min. The specific activities of AFQ1,AFM1, and AFP1 formation by microsomes ranged from 36-70, 161-326, and 252-426 pmol/mg protein/min, respectively. Mice fed a standard rodent chow diet showed evidence of microsomal and cytosolic enzyme induction when compared to mice fed a purified diet. The lack of substantial differences in enzyme specific activities between mouse strains suggests that interstrain variations in the hepatocarcinogenic effects of AFB1 in mice should not be large. PMID- 1910209 TI - Grand gamble on fruit fly learning. PMID- 1910217 TI - Soluble CD8, IL-2 receptor, and tumor necrosis factor-alpha levels in steroid resistant acute graft-versus-host disease. Relation with subsequent response to anti-IL-2 receptor monoclonal antibody treatment. AB - Serial determination of soluble CD8 (sCD8), soluble IL-2 receptors (sIL-2R), and tumor necrosis factor-alpha serum levels were performed in bone marrow transplant patients upon initiation, day 0 (D0) and at D10 of an anti-IL-2 receptor (alpha chain) monoclonal antibody (B-B10) in vivo treatment for steroid-resistant grade greater than or equal to 2 acute graft-versus-host disease (aGVHD). D0 and D10 sCD8 serum levels correlated strongly with response to B-B10 treatment (p = .003 and .001, respectively); 76% of the patients with D0 sCD8 levels less than 500 U/ml responded favorably to B-B10 treatment, versus only a 30% response if the sCD8 levels were greater than 500 U/ml (p = .02). Likewise, D0 tumor necrosis factor-alpha levels significantly correlated with subsequent response to B-B10 treatment (p = .03). D0 sIL-2R levels were not significantly different in B-B10 responsive and nonresponsive aGVHD patients. These results suggest that the serial determination of sCD8 and TNF serum levels could provide valuable predictive information as to steroid-resistant aGVHD responsiveness to anti-IL-2R treatment. PMID- 1910220 TI - The in vivo excystation of Sarcocystis gigantea and S. tenella sporocysts. AB - In vivo studies on the excystation of Sarcocystis gigantea and S. tenella sporocysts indicated that this process was, as in vitro, a diphasic one involving both pretreatment and treatment phases. The studies also tended to support in vitro observations that the requirements for the excystation of these two species are quite different. The results suggested that for neither species was the pretreatment stimulus likely to be provided by conditions in the rumen alone. However, exposure to abomasal conditions only induced moderate levels of excystation in both when they were subsequently treated with trypsin and bile. For S. gigantea, 0.25 to 4 h abomasal exposure was most effective; for S. tenella, 24 hours. The stimuli necessary to complete the excystation process could, apparently, be provided by 1 h placement in the duodenum for S. gigantea but not for S. tenella. PMID- 1910219 TI - Re-examination of the mineral supplement associated with a 1972 anthrax outbreak. PMID- 1910222 TI - A simple field diagnostic smear test for bovine besnoitiosis. AB - A fast and inexpensive skin biopsy smear was used for confirming suspected clinical cases of bovine besnoitiosis. The technique was based on the demonstration of Besnoitia besnoiti bradyzoites (cystic stages), which appeared stumpy, each organism 6.2 microns by 3.1 microns in size, or banana-shaped, 7.7 microns by 1.5 micron in affected skin smears. A more rapid non-surgical technique, scleral conjunctival scraping, revealed similar bradyzoites, thus enhancing the diagnostic value of conjunctival cysts in more chronic infections. The technique will aid prompt management decisions to contain suspected outbreaks in herds not routinely served by tissue-processor-equipped diagnostic laboratories. PMID- 1910221 TI - Cross-reactions between crude antigens of larval Taenia solium (Cysticercus cellulosae) and other helminths of pigs. AB - A crude antigen extract of larval Taenia solium was shown by immunodiffusion (ID) and immunoelectrophoresis (IEP) to cross-react with rabbit antisera against pig serum proteins and larval T. hydatigena, and by enzyme-linked immunosorbent assay (ELISA) with antisera against pig serum proteins, Fasciolopsis buski, larval T. hydatigena, hydatid cyst, Hymenolepis diminuta and Dipylidium caninum. Immunoblotting demonstrated that the crude antigens extract contained epitopes of pig serum proteins of 48 and 66 kDa. The crude extract also contained a subunit of antigen B (95 kDa) which was also found in T. hydatigena and H. diminuta. Immunoperoxidase and indirect immunofluorescence studies showed that cross reacting antigens were distributed mainly on the tegument of T. solium. PMID- 1910226 TI - [The heterogeneity of formed collectives in susceptibility to meningococcal adhesion]. AB - 4 patients with meningococcal infection and 141 meningococcal carriers were examined. The authors study heterogeneity of human population concerning susceptibility or stability of erythrocytes to adhesive influence of meningococci. In 17.4% of cases erythrocytes were highly susceptible to adhesion of meningococci, in 20.4% were stable to this influence, in 62.2% were moderately susceptible. The highest susceptibility of erythrocytes (out of statistics) was marked at the patients of Kirghiz and Tadjik nationalities. These indexes have the same statistic frequency for the persons with different blood groups (system ABO), independently of their rural or urban place of residence. The high susceptibility of erythrocytes (0.25 GAE or less) to adhesion of meningococci is three times more frequent among the persons with meningococcal infection and carriers of meningococcus. This connection may be regarded as a predisposition of the organism for the infection. Thus, the susceptibility of erythrocytes to adhesion of meningococci gives the possibility to determine the persons who need an urgent immunization at the forming collectives. PMID- 1910223 TI - Responses of peripheral blood mononuclear cells in calves infected with Theileria sergenti. AB - The role of peripheral blood mononuclear cell (PBMC) in Theileria sergenti infected calves was studied by various in vitro assay systems. Proliferation of T cells in mixed lymphocyte protozoa culture (MLPC) increased with parasitemia, and the addition of monoclonal antibodies against T. sergenti merozoites in this MLPC enhanced the response. However, the addition of antibody-positive autologous serum resulted in the suppression of the response. Cell-mediated cytotoxicity of PBMC increased after peak parasitemia. This cytotoxicity increased on co cultivation of PBMC with T. sergenti merozoites, but the addition of autologous serum suppressed the response. PMID- 1910218 TI - Tissue and serum insulin-like growth factor I (IGF I) concentrations in rats subjected to temporary protein-energy malnutrition early in life. AB - Rats subjected to temporary protein-energy malnutrition and subsequent nutritional rehabilitation remain smaller than adequately fed animals, have a subnormal insulin secretion and persisting cellular hypoplasia in several tissues. This investigation studies whether impaired production of insulin-like growth factor I (IGF I) is another persisting consequence of malnutrition. Rats were subjected to severe protein-energy malnutrition between 3 and 6 weeks of age and subsequently fed adequate diet up to 12 weeks of age. Serum and tissue samples for analysis of IGF I were obtained at 12 weeks of age. IGF I concentrations were similar in serum, heart, liver and lung of previously malnourished and control rats. In the kidneys of previously-malnourished rats the IGF I concentration was twice that of control rats. Results suggest that during protein-energy malnutrition and subsequent nutritional rehabilitation IGF I tissue concentrations are primarily regulated by the prevailing plane of nutrition. It is speculated that the temporary protein-energy malnutrition blunts the cellular capacity for IGF I production and, except in the kidney, prevents increased IGF I tissue concentrations and associated compensatory growth. PMID- 1910225 TI - [Platelet satellitosis]. AB - Platelet satellitism (PS) is a rare phenomenon described sporadically in the literature. It involves adhesion of thrombocytes sensitized by antibodies to leucocytes and is observed in vitro in EDTA anticoagulated blood. The authors' contribution to the problem is the observation of special thrombocyte aggregates surrounding neutrophils resembling comet tails, as well as the fact that the authors observed the formation of aggregates surrounding also lymphocytes and eosinophil cells. PMID- 1910224 TI - Immunoprophylaxis against Theileria annulata with protein from plasma membrane of infected lymphoblasts. AB - Cross-bred (Bos taurus male x Bos indicus female) calves were protected against the homologous sporozoite-induced challenge of Theileria annulata when immunised with protein from the plasma membrane of macroschizont-infected lymphoblasts of allogeneic origin. However, such protection was parasite-strain specific with the plasma membrane originating from lymphoblasts infected and transformed by the same isolate of T. annulata sporozoites. No protection ensued when the infected lymphoblasts and sporozoites were from immunologically different isolates of T. annulata. There was enhanced proliferation of cells and evidence for lymphokine, originating from antigen-sensitised lymphocytes, demonstrable as macrophage migration inhibition factor in peripheral blood lymphocytes of the calves immunised by plasma membrane protein and challenged by sporozoites of homologous origin. PMID- 1910227 TI - [Evaluation of drug therapy in epilepsy]. AB - Supposing that in evaluation of therapeutical efficacy of the definite antiepileptics the most important is its clinical effect, the aim the study was to analyse retrospectively correlation of clinical effects, EEG characteristics and serum carbamazepine concentration in a group of patients with subtherapeutical and in a group with therapeutical antiepileptic concentrations. The results of the study have shown no positive direct correlation among clinical effects, EEG characteristics and serum drug concentrations. It has been concluded that in evaluation of therapeutical carbamazepine efficacy of the essential importance is its clinical effects. PMID- 1910229 TI - The disposition of carbaryl in the hepatopancreas, haemolymph and embryos of the viviparous scorpion, Heterometrus fulvipes (Koch) during gestation. AB - 1. The disposition of carbaryl in the hepatopancreas and haemolymph of maternal animals and embryos of H. fulvipes (scorpion) after administration of a single sublethal dose was studied by g.l.c. 2. High levels of carbaryl were observed in haemolymph at 10 min, and in hepatopancreas at 1 h after administration. About 90% of the residues in the hepatopancreas were eliminated by 24 h. 3. In embryos high levels were noticed 6 h after administration and only 60% of the accumulated carbaryl was eliminated by 24 h. Carbaryl residues were observed in embryos even 1 week after administration. PMID- 1910228 TI - Clinical and cost effectiveness of prophylactic parenteral penicillin in the care of simple wounds undergoing suture repair. AB - Physicians working in casualty and outpatient departments where adverse conditions prevail often prescribe antibiotic prophylaxis routinely at the time of suture repair of simple wounds. To evaluate this practice, we performed a randomized, controlled study of parenteral chemoprophylaxis of simple wounds undergoing suture repair. Uncomplicated wounds were randomized to either treatment with a combination of benzathine penicillin (2.4 million units) and procaine penicillin (2.0 million units) intramuscularly, or a control group. At the time of suture removal, seven days later, all wounds were reviewed for signs of infection. Of 320 patients enrolled in the study, 173 (54.1%) returned for review. Among treated wounds, 75 of 81 (92.6%) were healing, compared to 79 of 92 (85.9%) controls (p = 0.24). A significantly higher rate of healing was observed when wounds repaired nine or more hours after injury and involving the arms, legs, or trunk were treated (22 of 23, 95.7%) compared to those in whom prophylaxis was omitted (20 of 30, 66.7%) (p = 0.03). Wounds involving the head, and wounds repaired within nine hours after injury had a high rate of healing (greater than 90%), whether prophylaxed or not. Based on a 30% higher healing rate for the patients who benefited from treatment (arm, leg, trunk wounds repaired after nine or more hours), the drug cost of implementing prophylaxis for this group alone was more than five times that of an expectant, non-prophylactic strategy. These results serve to remind practitioners of the possibility that a clinically effective mode of therapy may not necessarily be cost-effective in the delivery of health care. PMID- 1910231 TI - [Comment on the article: Ascorbic Acid Metabolism in Clawed Monkeys using the 14C elimination Method, 29:192-196]. PMID- 1910230 TI - Chronic ethanol consumption causes increased glucuronidation of morphine in rabbits. AB - 1. Male rabbits were given an i.p. injection of 15 mg/kg morphine and plasma concentrations of morphine and morphine-3-glucuronide (M3G) were simultaneously quantified by h.p.l.c. After 14 days of 10% ethanol in the rabbits' drinking water, a second injection of morphine was administered and plasma concentrations were determined again. 2. Morphine plasma clearance increased significantly by 42% after ethanol treatment. The area under the plasma concentration time curve (AUC) for morphine decreased by 23% while the AUC for the glucuronide increased by 22%. 3. The ratio of the AUCs (glucruonide/morphine) increased by 72%. These results demonstrate that chronic ethanol treatment of rabbits results in increased clearance of morphine after an i.p. dose. The increase in clearance is most likely due to induction of UDP-glucuronosyltransferase isozymes by ethanol. PMID- 1910232 TI - [Effects of diltiazem in acute and long-term administration]. AB - In 16 patients with unstable angina pectoris haemodynamic and clinical effects of diltiazem were investigated. In a second group patients (n = 11) with unstable or therapy-refractory course the long-term effect was tested. The acute intervention with injected and infused diltiazem via an improved oxygen balance due to decreased minute work and reduced product of cardiac frequency and pressure stabilized the clinical picture from the haemodynamic aspect. The decreases of the ST segment were significantly lower. In the long-term use a significant influence on the frequency of angina pectoris with increase of the range of efficacy by one NYHA-state was the result. Diltiazem can be regarded as alternative medicament in unstable phases and in therapy-refractory courses of the chronic coronary heart disease. PMID- 1910233 TI - Clinico-immunological trials of Pseudomonas aeruginosa vaccine. AB - Pseudomonas aeruginosa vaccine (PV) containing predominantly cell-wall protein protective antigens was tested for safety and immunogenicity by immunization of 119 volunteers. The criteria for safety and immunogenicity were the absence of serious post-vaccinal reactions or complications either during immunization or 12 months later. There were mild (19 donors or 15.9%) and moderate (three donors or 2.5%) febrile reactions after immunization and in two volunteers the body temperature increased up to 38 degrees C, however it decreased to normal values within 24 h. We observed in 43 (36.1%) of volunteers mild and in five (4.2%) moderate local reactions which disappeared within 24 h. Using the ELISA and passive mouse protection test it was shown that PV induces the formation of specific antibodies. A high level of specific antibodies persisted for the 5 month period of observation. The antibody titres increased in 94-97% of volunteers and moreover in 45.6% the antibody titres (the number of ELISA units) increased 2.5-3-fold and more. Anti-P. aeruginosa plasma was used for the treatment of 46 patients with severe forms of P. aeruginosa infection (40 adults and six infants aged up to 2 years) and 87% of the patients recovered. PMID- 1910234 TI - [The pathology and pathogenesis of experimental Mycoplasma hyorhinis infection of piglets with and without thermomotor stress. 2. Electron microscopic study results]. AB - Electron microscopic investigations on the respiratory tract of piglets with and without Mycoplasma hyorhinis infection (10th day of life) partly combined with swim stress (15 degrees C water temperature) (n = 20/20) yielded the following results: colonization of Mycoplasma hyorhinis in the ciliary zone of trachea and bronchi in 15 out of 40 piglets (37.5%); the evidence rate of Mycoplasma hyorhinis in pneumonic lungs (8 out of 12 = 66.7%) was significantly higher than in nonpneumonic lungs (7 out of 28 = 25.0%) and highest in experimentally infected piglets with swim stress (9 out of 16 = 56.2%). Ultrastructural lesions: loss of cilia; bleb-formation; hydropic degeneration and desquamation of ciliary cells; the occurrence of cilia-free and immature epithelial cells; alveolar collapse; microatelectasis; oedematous swelling of pneumocyte I; accumulation of surfactant in the alveoli; hyperplasia of pneumocyte II; exudation of mononuclear macrophages and neutrophils with numerous digestion vacuoles; several lymphocytes and plasma cells, only a little lymphohistiocytic interstitial and peribronchial infiltration. Phagocytized mycoplasmas were found within the resorption vacuoles of neutrophils in the tracheobronchial area, for this once in alveoli, not (more) against in alveolar macrophages. The results were discussed with regard to etiology and pathogenicity of enzootic pneumonia in pigs. PMID- 1910236 TI - A technique for continuously monitoring hormone levels in lactating sows and results obtained using it to study LH release. AB - A technique for collecting continuously blood was successfully applied for the first time in lactating sows. A double-lumen catheter consisted of an internal tubing for delivering an anticoagulant (heparin-saline) and an outer tubing for blood collection. An automatic system, composed of a blood withdrawal pump, an anticoagulant infusion pump and a fraction collector, was connected to the catheter and operated for 12 h on Days 10 and 20 of lactation. Blood samples were collected continuously at a rate of 1 ml per min from four sows. Each fraction consisted of 4 ml blood except during nursing periods when 1 ml blood per fraction was collected. In this study, aliquots of plasma were combined to form pooled 8-min samples for the measurement of the concentrations of LH. Average and base levels of LH, number of LH pulse(s)/12 h and pulse durations were calculated for all pooled samples, all even-numbered samples and all odd-numbered samples. Average and base levels of LH and the number of LH pulses were slightly higher on Day 20 than on Day 10 of lactation. The LH-pulse duration varied between animals, with the value for one of the sows diverging greatly from those of the others. When only every second sample was considered, the LH-pulse rate appeared to be slightly lower. PMID- 1910235 TI - Cyclic variations in intraluminal pressure in the isthmus of the oviduct in unrestrained gilts. AB - Cyclic variations in intraluminal pressure in the isthmus of the oviduct in unrestrained gilts were observed. During proestrus and through the first day of oestrus, base pressure and total pressure increased reaching a high pressure on the second half of day 1 (first day of standing oestrus) after which a decrease was seen with a low base pressure recorded on the second half of day 3 and a low total pressure appearing on the second half of day 3 lasting through day 4. The frequency of the phasic pressure fluctuations in the isthmus also increased during proestrus and reached a high value on the first half of day 2. The frequency then declined to a low value on day 4. The pattern in which the phasic pressure fluctuations were arranged changed from predominantly wavy during proestrus and through the first half of day 2 to progressively more irregular in appearance after day 2. Outbursts of increased intraluminal pressure with varying propagation directions occurred with a fairly high frequency from the second half of day 2 and through day 3. PMID- 1910237 TI - Comparison between a modified haemocytometric technique and electronic counters in goat blood cell counting. AB - Dilutions of goat blood with Hayem-Jorgensen's fluid ranging from 1:200 to 1:1,000 were used for haemocytometer counting of red blood cells (RBC) in 27 goats. The optimal dilutions were 1:400-1:500. Correlation studies between the results obtained by the haemocytometer and the Coulter counter red blood cell (RBC) and white blood cell (WBC) counts were performed in 551 goat blood samples. The haemocytometer RBC counts were 5.63% higher and WBC counts 2.79% lower than those of the electronic counter. The method of blood cell counting therefore influences the clinical haematological diagnoses and reference values in domestic animals. New cell counters specifically designed to measure cells of small volumes, e.g. goat erythrocytes, are needed. PMID- 1910238 TI - Type 1 abomasal ulcers in dairy cattle. AB - Abomasa from 912 randomly selected cows were examined; specimens were obtained at the local slaughter house on 35 days spread over one year. Abomasal lesions were assessed macroscopically and histologically. Additionally, haematological and blood chemistry (urea, aspartate aminotransferase, potassium, chloride, calcium) evaluations and the determination of rumen chloride concentration were performed. Of the 912 abomasa examined, 187 (20.5%) had ulcerative lesions of the mucosa. Lesions were classified from 1 to 4 based on severity as described by Whitlock (1980). All ulcers were classified as type 1 (erosions and non-perforating ulcers); thus, further division into four subtypes 1 a, 1 b, 1 c and 1 d was carried out. Fifty-six abomasa had minimal mucosal defects which were classified as type 1 a. Deeper erosions combined with local hemorrhage, classified as type 1 b, were observed in 54 abomasa. Type 1 c were crater-like ulcers and were seen in 61 abomasa. Sixteen abomasa had type 1 d ulcers which included two forms: ulcers with radial wrinkles converging on a central point, and ulcers with perforated folds. Types 1 a and 1 c occurred mainly in the pyloric region, and types 1 b and 1 d were observed mainly in the fundic region. Type 1 abomasal ulcus could not be diagnosed based on alterations in haematological or blood and rumen chemistry values. PMID- 1910240 TI - Effect of noradrenaline on smooth muscle strips from the reticular groove of adult cattle. AB - The effect of noradrenaline (NA) on smooth muscle strips from the reticular groove of adult cattle was studied. The mechanical activity of the muscle strips was recorded isometrically. Noradrenaline caused concentration dependent (1.1 x 10(-6)-55 x 10(-6) mol/l) contractions of both the transversal muscle strips from the floor and the longitudinal muscle strips from the lips of the reticular groove. This excitatory effect of noradrenaline was antagonized by the alpha 1 receptor antagonist prazosin (10(-8) mol/l) and by higher concentrations of the alpha 2-receptor antagonist yohimbine (10(-6) mol/l) and atropine (10(-5) mol/l). Tetrodotoxin (5 x 10(-6) mol/l) and latrotoxin did not affect the contractile response of the muscle strips to noradrenaline (55 x 10(-6) mol/l). Furthermore, strips stored for 24 hours in Tyrode's solution at 4 degrees C without oxygen supply maintained their full sensitivity to noradrenaline. Propranolol (10(-4) mol/l), a beta-receptor antagonist, led to a significant increase of the contractions induced by noradrenaline (55 x 10(-6) mol/l). These results suggest that noradrenaline increases the tone of the smooth muscle of the reticular groove via alpha-adrenergic receptors and decreases its tone via beta-adrenergic receptors. Both receptor types are located on the smooth muscle cells. The alpha 1-receptor mediated effect appears to be predominant. PMID- 1910239 TI - Quantitative buffy coat analysis related to adrenocortical function in horses during a three-day event competition. AB - This study was carried out to investigate stress induced in a cross-country by measuring plasma cortisol and to compare the changes in cortisol level with the leucocytic changes measured with the quantitative buffy coat (QBC) analysis, which is a new method applicable in field conditions for the evaluation of haematological parameters in horses. Seven healthy horses competing in a national three-day event were investigated. Venous blood was sampled under resting condition, 2 min and 180 min after the completion of the cross-country and analysed for haematological parameters, plasma cortisol, protein and lactate levels. Immediately after the event, there was a significant increase in all values except in the granulocytes (Gr) to lymphocytes-monocytes (LM) ratio. 180 min after the event, all the parameters returned to their resting levels while white blood cells (WBC), Gr and Gr/LM ratio were significantly higher with respect to their resting values. A high correlation (r = 0.82) was found between the relative increase in plasma cortisol levels 2 min after exercise and the relative increase in Gr/LM 180 min after exercise. Therefore it was concluded that the Gr/LM ratio measured 180 min after exercise with the QBC analysis is a reliable index to estimate the plasma cortisol levels measured 2 min after exercise. This new technique could consequently be used in order to evaluate, in field conditions, the exercise-induced stress. PMID- 1910241 TI - Leukocyte profile in growing dwarf and landrace kids. AB - Total and differential leukocyte count profiles were studied in 62 clinically healthy Danish landrace kids and 34 clinically healthy dwarf kids from birth to 12 months of age in seven Danish herds. The objective was to determine the reference values in the two breeds and the influence of age, sex and environment and whether there are any breed differences. Parametric (mean +/- 2 standard deviations) and the nonparametric (5th to 95th percentile interval) values for each leukocyte type were closely related. The medians were very close to the means. The number of leukocytes was low in neonates, 7.1 +/- 1.5 and 7.0 +/- 2.1 x 10(9)/l in dwarf and landrace kids respectively. Values increased with age to 18.7 +/- 2.1 and 13.4 +/- 3.1 x 10(9)/l in the two breeds respectively at 8-12 months of age. There were significant differences in leukocyte counts between the breeds at 1-2 and 8-12 months of age and at 2-4 months between herds within the breeds. The number of lymphocyte and neutrophil cells were 2.6 +/- 0.8 and 3.9 +/ 1.1 x 10(9)/l respectively in neonatal dwarf and 4.1 +/- 1.5 and 2.3 +/- 1.1 x 10(9)/l respectively in landrace kids. Very high numbers of these cells were observed in dwarf and landrace kids respectively within 8 months, 10.7 +/- 1.1 and 8.2 +/- 3.3 lymphocytes and 6.8 +/- 1.7 and 4.4 +/- 2.6 x 10(9)/l neutrophils for the two breeds. Significant differences between the ages (within the breeds), breeds (within similar ages) and herds (within breeds in kids of similar ages) were observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1910243 TI - Effect of insulin-like growth factor I on steroidogenesis in cultured human granulosa cells. AB - The effect of IGF-I on steroidogenesis in human granulosa cells was studied. Granulosa cells were obtained from follicles of both natural and stimulated cycles. The cells were cultured 4 to 6 days and the effect of IGF-I (1 to 100 micrograms/l) on basal, LH- and FSH-stimulated steroidogenesis was studied. It was found that in granulosa cells from follicles of natural cycles, FSH as well as IGF-I significantly stimulated progesterone and estradiol production in a majority of the experiments. A synergistic effect of FSH and IGF-I could be seen when low (1 and 10 micrograms/l) concentrations of the two hormones were used. Also in granulosa luteal cells from stimulated cycles a stimulatory effect of IGF I on estradiol as well as progesterone production was observed. The present results suggest that IGF-I in combination with gonadotropins has a physiological role in the human follicle in controlling differentiation of the granulosa cells. PMID- 1910242 TI - Effects of decreasing exogenous GnRH pulse frequency on FSH and inhibin secretion in men with idiopathic hypogonadotropic hypogonadism. AB - The potential importance of GnRH pulse frequency modulation and steroid or inhibin negative feedback in the selective control of pituitary FSH secretion was investigated in 5 adult men with idiopathic hypogonadotropic hypogonadism in whom plasma testosterone has been previously normalized by pulsatile GnRH therapy. The effects of decreasing frequency of pulsatile iv GnRH administration from 2- to 4 hourly for 7 days were examined at constant GnRH bolus dose or constant daily dose and also with interrupted gonadal steroid feedback using a combination of an anti-androgen (flutamide 250 mg t.i.d.) and an aromatase inhibitor (aminogluthetimide 125 mg b.d.) orally for a further 7 days. Slowing GnRH pulse frequency from 2- to 4-hourly did not alter mean plasma FSH at constant bolus dose or constant total daily doses of GnRH. In two subjects with subnormal but not in another two with normal testicular volumes, FSH rise was observed when the 4-hourly GnRH pulse frequency was combined with the interruption of steroid feedback. These results are not compatible with a major role for GnRH pulse frequency modulation in the regulation of pituitary FSH secretion in the presence of normal gonadal steroid feedback. Irrespective of FSH concentrations, plasma inhibin immunoactivity did not change significantly with the alteration in GnRH pulse frequency. The role of inhibin in the control of FSH therefore remains undefined in men. PMID- 1910245 TI - Combined growth hormone and gonadotropin treatment for ovulation induction in patients with non-responsive ovaries. AB - Four anovulatory patients who did not respond to large doses of hMG over 18-33 days were co-treated in subsequent cycles with human growth hormone. Treatment with growth hormone markedly raised serum insulin-like growth factor concentrations. Two patients had a dramatic ovarian response within 7 days of co treatment; two menopausal patients did not respond. This combined therapy may be of practical value for ovulation induction in non-menopausal patients with non responsive ovaries. PMID- 1910246 TI - Gonadotropin releasing hormone agonist therapy and its effect on bone mass. AB - The effects on bone mass of a 6 month therapeutic cycle with a gonadotropin releasing hormone agonist (GnRHa) were studied in 22 patients, ten affected by pelvic endometriosis and 12 by uterine fibroids. All patients were subjected to preliminary full examinations to confirm their diagnosis (laparoscopy for the endometriosis group and precise ultrasound volume measurements for uterine fibroids group). Before the beginning of treatment, bone mineral density (BMD) was measured in each patient both on the distal third of the forearm, with single photon absorptiometry, and on the lumbar spine (L1-L4), with dual photon absorptiometry. The gonadotropin releasing hormone agonist used was buserelin. In the first week of therapy 0.5 mg of the drug was administered subcutaneously thrice daily. In the following 25 weeks the same drug was given intranasally, at a dosage of 300 micrograms again three times a day. Bone mass measurements, both at the peripheral and at the axial site, were repeated at the end of the 26-week therapeutic cycle and then again 6 months later. At the 26th week, a significant decrease of BMD was observed at both sites. The loss was 1.5% (p less than 0.05) on the lumbar spine, and 2.1% (p less than 0.05) on the radius. No bone mass restoration took place in the following 6 months. On the contrary, a less significant but discernible trend towards a further bone loss was apparent in the BMD values measured 6 months after the end of therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1910247 TI - Ovulation induction with human menopausal gonadotropins--a changing scene. AB - The aim of human menopausal gonadotropin treatment (hMG), to simulate normal follicular development by injecting FSH and LH and induce follicular rupture with hCG, is rarely met. Multiple follicular development occurs because hypothalamic pituitary feedback is bypassed. This, exacerbated by the long half-life of hCG, causes the principal complications of hMG therapy--multiple pregnancy and hyperstimulation. The initial use of hMG in pituitary deficiency has been widened to include failure to respond to clomiphene, polycystic ovaries, 'unexplained infertility' and in vitro fertilization. Reported pregnancy rates, incidence of hyperstimulation and of multiple pregnancy vary widely. We reviewed the results of hMG therapy from 1977 to 1989 in 260 consecutive women with clomiphene resistant infertility. Conception and live birth rates after six treatment cycles were 45.7% and 43.3%, respectively and were influenced by the cause of infertility, age, weight and sperm parameters. The miscarriage rate was 18.6% and multiple pregnancy rate 19.3%. The conception rate fell during the 12-year period in all groups except those with regular anovulatory cycles. Over this period, age, weight and male subfertility increased in patients referred to us. hMG is an effective and safe treatment for women with clomiphene-resistant infertility and patent tubes. PMID- 1910244 TI - Effect of insulin-like growth factor I on gonadotropin release from the hypothalamus-pituitary axis in vitro. AB - The effects of insulin-like growth factor-I on gonadotropin release were studied using primary culture of rat anterior pituitary cells incubated with IGF-I (20 5000 micrograms/l) and a hypothalamus-pituitary perifusion system, in which either the mediobasal hypothalamus-pituitary unit or the pituitary were perifused with IGF-I (20-2000 micrograms/l). In primary cultures of rat anterior pituitary cells, IGF-I (2000 micrograms/l) caused a significant increase in the release of both LH (46% increase) and FSH (27% increase). It also caused a significant decrease in the cellular content of LH (9%) and FSH (19%). Its effects in stimulating gonadotropin release were suppressed by administration of anti IGF-I receptor antibody (1 mg/l). In the perifusion system, IGF-I (2000 micrograms/l) did not affect the LH release from the hypothalamus-pituitary or pituitary alone. However, it caused a significant increase in the GnRH (10(-9) mol/l) stimulated LH release from perifused pituitary. These data suggest that IGF-I enhances pituitary gonadotropin release via the IGF-I receptor, but its effect on the hypothalamus was not confirmed. PMID- 1910248 TI - Different susceptibility of lung cell lines to inhibitors of tumor promotion and inducers of differentiation. AB - Histologically distinct lung tumor and normal cell lines were treated with a variety of potential inhibitors of cell growth such as inducers of cell differentiation, inhibitors of protein kinase C and inhibitors of tumor promotion. The response was assessed by 3H thymidine incorporation and cloning efficiency. Both phorbol retinoate acetate and mezerein stimulated growth in lung normal cell lines (human fibroblastic PEH cells and rat epithelial TP9 cells) while inhibiting growth in lung tumor cell lines (human small-cell cancer-derived cell line IRSC-10M and adenocarcinoma-derived cell line A549). Likewise, the hydrophobic peptide melittin did not inhibit growth and cloning efficiency of normal cells at 1 microM, a concentration which prevented proliferation in tumor cells. Protein kinase C inhibitors, chlorpromazine, trifluoperazine and 1-(5 isoquinolinylsulfonyl) 2-methylpiperazine, were much more effective on proliferation of IRSC-1OM than of A549 cells. In contrast, the latter cells were more susceptible to anti-promoters such as glycyrrhetic acid, an anti inflammatory agent, and 3,4',2', 4'-tetrahydroxychalcone or 2,3,5-trimethyl-6 (12 hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone, two inhibitors of lipoxygenase, a key enzyme in arachidonate metabolism. Our results provide evidence that small cell carcinoma-derived cells, in contrast with adenocarcinoma-derived cells, are growth-inhibited by protein kinase C inhibitors and poorly dependent on the arachidonate metabolism. This difference in responsiveness suggests that different growth signalling pathways are preferentially triggered in these histologically distinct lung tumor cell lines. As a consequence, the proper susceptibility of tumor cells to phenotype modifiers has to be taken into account in cancer therapy. PMID- 1910249 TI - Utilization of early Maillard reaction products by humans. AB - The paper reports results from balance trials with a total of 42 volunteers testing glycated casein samples containing the Maillard-(Amadori-) product fructoselysine (= FL, analysed as furosine). On a almost FL free diet only traces of FL were excreted. If test meals with 0.8-5.0 g FL were given, only 2.0-1.2% were found in the urine. In the feces of 3 persons eating 0.96 g FL in a single meal 2.6-5.6% were excreted. It is concluded that digestion is the main limiting factor for the uptake of FL. Possibly also the transit time of the ingesta through the gastro intestinal tract is important. Since there is no indication from animal studies for a utilization of FL it can be assumed that the microorganism in the hind gut decompose the main part of the not recovered more than 90% of FL. Obviously the bacterial flora is more active and able to attack such components as assumed until now. PMID- 1910250 TI - Improvement in the nutritional quality of bread. AB - To assess whether the dipeptide N-epsilon-(gamma-L-glutamyl)-L-lysine (glutamyl lysine) can serve as a nutritional source of lysine, we compared the growth of mice fed (a) an amino acid diet in which lysine was replaced by six dietary levels of glutamyl-lysine; (b) wheat gluten diets fortified with lysine; (c) a wheat bread-based diet (10% protein) supplemented before feeding with lysine or glutamyl-lysine (0, 0.75, 1.50, 2.25, and 3% lysine HCl-equivalent in the final diet), not co-baked and (d) bread diets co-baked with these levels of lysine or glutamyl-lysine. With the amino acid diet, the relative growth response to glutamyl-lysine was about half that of lysine. The effect of added lysine on the nutritional improvement of wheat gluten depended on both lysine and gluten concentrations in the diet. With 10 and 15% gluten, 0.37% lysine HCl produced a marked increase in weight gain. Further increase in lysine HCl to 0.75% proved detrimental to weight gain. Lysine HCl addition improved growth at 20 and 25% gluten in the diet and did not prove detrimental at 0.75%. For whole bread, glutamyl-lysine served nearly as well as lysine to improve weight gain. The nutritive value of bread crust fortified or not was markedly less than that of crumb or whole bread. Other data showed that lysine or glutamyl-lysine at the highest level of fortification, 0.3%, improved the protein quality (PER) of crumb over that of either crust or whole bread, indicating a possible greater availability of the second-limiting amino acid, threonine, in crumb. These data and additional metabolic studies with U-14-C glutamyl-lysine suggest that glutamyl-lysine, co-baked or not, is digested in the kidneys and utilized in vivo as a source of lysine; it and related peptides merit further study as a sources of lysine in low-lysine foods. PMID- 1910251 TI - Is the airway epithelium responsible for histamine metabolism in the trachea of guinea pigs? AB - The aim of the study was to investigate whether or not the epithelium plays an active role in histamine metabolism, via the histaminase and/or methyltransferase pathways. Isolated tracheas from guinea pigs sensitized to egg albumin (EA) were used. The epithelium was either left intact or removed from the preparations. The tracheal tubes were mounted in a chamber, allowing estimation of smooth muscle tension, and perfused with buffer. In some experiments the perfusate was collected for determination of histamine and methylhistamine. Mepyramine was used to evaluate the contribution of histamine to the EA-induced contraction. Mepyramine reduced the contraction by 90% when the epithelium was removed; with intact epithelium the reduction was 47%. Aminoguanidine, a histaminase inhibitor, significantly potentiated the response to EA when the epithelium was left intact. Traces of methylhistamine were detected in tissue extracts and perfusates. We conclude that histaminase is present in the preparation and that it can contribute to the inhibitory effect of the epithelium by means of histamine degradation. PMID- 1910252 TI - [A role of cultured bovine lens epithelial cells in the fibrinolytic system]. AB - The release of plasminogen activators (PAs) and plasminogen activator inhibitor (PAI) from cultured bovine lens epithelial cells was investigated, in an attempt to study the effect of lens epithelial cells on the fibrin deposit and fibrinolytic process on the surface of IOL. Cultured bovine lens epithelial cells released tissue plasminogen activator (t-PA) and type 1 plasminogen activator inhibitor (PAI-1). t-PA activity was completely inhibited by PAI-1. These findings suggest that lens epithelial cells cause suppression of fibrinolysis in the anterior chamber of the eye. PMID- 1910253 TI - [A case of metastatic Enterococcus faecalis endophthalmitis]. AB - We reported a case of successful treatment of early-stage metastatic endophthalmitis caused by Enterococcus faecalis with vitrectomy and lensectomy. The case was a 50-year-old male with poorly controlled diabetes. Following T-tube drainage for a necrotic cholecystitis operation, he developed iridocyclitis in both eyes as well as fever. At the time of his first visit to our clinic, his right eye had already lost light perception. His left eye had visual acuity recognizing of hand movement, marked uveitis, complicated cataract, and dense vitreous opacity. As gram positive cocci were isolated from the aspirated vitreous, we conducted lensectomy and vitrectomy under irrigation of antibiotics. With systemic postoperative antibiotics and human immunoglobulin, the patient showed remarkable improvement in his ocular fundus. By 60 days after the operation, the visual acuity of his left eye recovered to 4/20. Metastatic Enterococcus faecalis endophthalmitis has almost nerve been reported in Japan. The diagnosis and treatment of this disease with a reference to the above findings were discussed. PMID- 1910255 TI - Tryptophan, tube-feeding, and hypoalbuminemia. PMID- 1910254 TI - Lipid-lowering diets in patients taking pravastatin, a new HMG-CoA reductase inhibitor: compliance and adequacy. AB - We examined seven 1-d diet records kept during 1 y by 272 men and women instructed to follow a lipid-lowering diet while participating in a clinical trial of pravastatin, a new 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor. The mean percentage of calories from total fat and saturated, unsaturated, and monounsaturated fatty acids was similar throughout the year even though the patients knew they were taking an effective lipid lowering agent. However, the diets of greater than 40% of women included less than two-thirds of the recommended dietary allowance (RDA) of folic acid, vitamins B-6 and D, and calcium and zinc; in men, folic acid and zinc intakes were low. We conclude that patients comply with lipid-lowering diets even when they know that they are receiving an effective serum lipid-lowering agent. However, for both men and women special attention should be given to the intake of several nutrients. PMID- 1910256 TI - Detection of rearrangement of immunoglobulin heavy chain and T-cell receptor beta chain in leukemic cells by restricted polymerase chain reaction. AB - Rearrangement of the immunoglobulin heavy chain and of the T-cell receptor beta subunit was analyzed by using restricted polymerase chain reaction (PCR). To differentiate between the germline configuration and the rearranged genome in a DNA sample extracted from lymphocytes, we compared the ratio of the amplified products. The intensity of amplification of the intron region (JHF) upstream of the first joining region was compared to the intensity of joining region 6 of the immunoglobulin heavy chain. The number of the amplification cycles in the PCR was designated in such a way that the ratio of JHF/JH6 was less than one in the rearranged configuration. As the concentration of clonal B-lymphocytes with the rearranged genome in the sample increased the amplification of the JHF intron proportionally decreased. We used the same approach for the two constant regions of the T-cell receptor beta chain. As one of the intron regions of the constant sequence became depleted by rearrangement so the amplification of the particular region decreased. Therefore, the absence or decreased concentration of a particular product of amplification indicated deletion and thus rearrangement of the genome in the leukemic B- or T-lymphocytes. The threshold of detection of cells with the rearranged genome on a photograph of agarose gel loaded with the particular amplified regions and staining with the ethidium bromide is less than 10% by densitometric tracing and 25-50% by visual evaluation. This novel approach allows the detection of the rearranged DNA sequences in a 2 day span. Hence, it can serve as a diagnostic tool for the identification of clonal expansion of lymphocytes in acute leukemias and lymphomas in particular and for the detection of deleted genomic regions in general. PMID- 1910257 TI - Treatment of thrombotic thrombocytopenic purpura using vincristine and factor VIII plasma free. PMID- 1910258 TI - Natural killer cells in pure red cell aplasia. PMID- 1910259 TI - A tRNA(Lys) mutation in the mtDNA is the causal genetic lesion underlying myoclonic epilepsy and ragged-red fiber (MERRF) syndrome. AB - Skeletal muscle mtDNA of three patients with mitochondrial encephalomyopathy, characterized clinically by myoclonic epilepsy and ragged-red fiber (MERRF) syndrome, has been sequenced to determine the underlying molecular defect(s). An A-to-G substitution of nt 8344 in the tRNA(Lys) gene, a substitution suggested to be associated with MERRF encephalomyopathy, was detected in these patients. Abnormal patterns of mitochondrial translation products were observed in the skeletal muscle of patients, consistent with the expected consequential defect in protein synthesis. The genealogical studies of the three patients, as well as mtDNA from one published MERRF patient and from nine other normal and disease controls, revealed that the tRNA(Lys) mutations in the MERRF patients have arisen independently. These observations provided evidence that the base substitution is a causal mutation for MERRF. PMID- 1910260 TI - Stability of cimetidine hydrochloride in Sondalis Iso enteral nutrition formula. PMID- 1910261 TI - Gas production of three brands of ceftazidime. AB - Two sodium carbonate formulations of ceftazidime (Tazidime and Tazicef) and a new arginine formulation (Ceptaz) were evaluated for gas production and bubble formation within the drug reservoir and extension tubing of a portable infusion pump during a 24-hour delivery cycle. Triplicate samples of each brand of ceftazidime were studied under identical conditions. All formulations were constituted and diluted with sterile water for injection to a concentration of approximately 33 mg/mL, drawn into syringes, and expelled into infusion-pump drug reservoirs. Triplicate samples of degassed Tazidime and Tazicef were evaluated in the same manner. In one set of triplicate experiments, reservoirs for each formulation were attached to portable infusion pumps immediately after filling at room (23 degrees C) temperature and were programmed to deliver 25 mL over one hour every eight hours for a 24-hour delivery cycle. In a second experiment, reservoirs containing triplicate samples of each product were refrigerated (3 degrees C) for 24 hours before they were attached to the pumps for dose delivery. Visual observations were made for all pumping devices. In addition, multiple vials of each formulation were constituted, and the headspace pressure of the various formulations was monitored to compare the pressure build-up due to carbon dioxide. The presence of carbon dioxide was confirmed by gas chromatography. Pressure build-up due to carbon dioxide formation occurred in the ceftazidime sodium carbonate vials only. The sodium carbonate formulations required degrassing to reduce gas and bubble formation to a manageable level after constitution. Additionally, drug was lost because of spewing of some samples during withdrawal from the vial.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1910262 TI - Relationship between head circumference and height in normal adults and in the nevoid basal cell carcinoma syndrome and neurofibromatosis type I. AB - Occipitofrontal circumference (OFC) was strongly correlated with height in 72 normal Caucasian men (r = 0.28, P = 0.018) and 78 women (r = 0.53, P less than 0.0001). OFC:height ratios were approximately normally distributed in each sex with a mean of 0.326 (standard deviation [sd] = 0.0139) in males and 0.335 (sd = 0.0177) in females. Relative macrocephaly (an OFC greater than the 95th centile for height) was seen in seven of nine probands with the nevoid basal cell carcinoma syndrome (NBCC), eight of 32 non-probands with NBCC, three of four neurofibromatosis type 1 (NF1) probands, and six of nine non-probands with NF1. Thirty-one percent of the non-proband NBCC cases had OFC less than the 50th centile for height, while none of the NF1 cases had this finding. Head size appears to be related to proband status in NBCC, while the evidence suggests that NF1 is a true macrocephaly syndrome. Objective detection of relative abnormalities in head size may aid in syndrome delineation and diagnosis. PMID- 1910263 TI - Chromosomal fragile site expression in dogs: I. Breed specific differences. AB - Peripheral blood lymphocytes from clinically normal Doberman pinscher and boxer dogs were cultured for folate-sensitive and, in preliminary studies, aphidicolin inducible fragile site expression. Both autosomal and X chromosomal fragile sites were observed in canine cells cultured under folate/thymidine depletion and in cells cultured in medium containing aphidicolin. Results from the three dogs evaluated for both folate-sensitive and aphidicolin-inducible fragile site expression showed that the frequency of fragile site expression was significantly (P less than 0.05) greater in cells cultured in medium containing aphidicolin than in cells cultured in folate/thymidine-depleted medium. Cells from the boxer dog expressed a high percentage (66.67%) of aphidicolin-inducible fragile sites in contrast to the Doberman pinscher dog in which only 21.10% of the lymphocytes expressed aphidicolin-inducible fragile sites. The frequencies of spontaneous and folate-sensitive fragile site expression did not vary significantly by breed of dog. Age of dog was significantly and positively correlated with frequency of folate-sensitive fragile site expression in dogs of the boxer breed, but not in dogs of the Doberman pinscher breed. The dog X chromosome expressed three folate sensitive and aphidicolin-inducible fragile sites. The G-band location of these three fragile sites showed homology with three recognized constitutive common fragile sites on the human X chromosome: Xp22, Xq21, and Xq27.2. Two specific autosomal fragile sites were identified, one on the distal end of the long arm of chromosome 1 and one on the distal end of the long arm of chromosome 8. Other autosomal fragile sites were also apparent but could not be assigned reliably to specific chromosomes. PMID- 1910264 TI - Chromosomal fragile site expression in dogs: II. Expression in boxer dogs with mast cell tumors. AB - Peripheral blood lymphocytes from boxer dogs with a history of cutaneous mast cell tumors were cultured for fragile site expression. As in a control group of dogs, cells from these dogs expressed folate-sensitive autosomal and X chromosome fragile sites. Cells from boxer dogs with mast cell tumors expressed the same three common fragile sites on the X chromosome as cells from control dogs. Three folate-sensitive autosomal fragile sites not observed in cells from the control dogs were identified in cells from boxers with mast cell tumors. These included fragile sites near the telomeres of the arms of chromosomes 3 and 4 and a fragile site on the distal half of chromosome 15. Cells from boxers with mast cell tumors showed a greater frequency of fragile site expression than did cells from control dogs, but this observation was attributed to an unintended selection bias for younger boxer dogs without mast cell tumors and older boxer dogs with mast cell tumors and an increased frequency of fragile site expression with increasing age in dogs of the boxer breed. PMID- 1910265 TI - Brief communication: immunoglobulin (Gm and Km) allotypes in two populations of Catalonia (Spain). AB - Serum samples from two populations of Catalonia, Spain, 208 from Olot (Gerona) and 209 from Tortosa (Tarragona), were typed for G1m (1, 2, 3, 17), G3m (5, 10, 11, 13, 14, 15, 16, 26), and Km (1). The Gm patterns of the Catalonian populations are characterized by the presence of four haplotypes, Gm 1,17;21,26 Gm 1,2,17;21,26 Gm 1,3;5,10,11,13,14,26 and Gm 3;5,10,11,13,14,26. The homogeneity for haplotype Gm 1,17;21,26 among our data and other European populations suggests the existence of an isofrequency line which starts from the Mediterranean zone of Iberian Peninsula and continues through the northwestern part of Europe. From this line a decreasing cline towards the south can be observed. For the haplotype Gm 1,2;17,21,26, affinities are observed between Catalonian populations and other populations from central Europe. This confirms the existence of a gradient towards low values from NW to SE. The presence of the typical Mongoloid haplotype Gm 1,3;5,10,11,13,14,26 is discussed in this paper. No significant differences in the frequencies of the Km1 allele were observed among the European populations. PMID- 1910266 TI - Personal spore sampling and indirect immunofluorescent test for exploration of hypersensitivity pneumonitis due to mould spores. AB - Sensitization to mould spores was investigated in six patients with hypersensitivity pneumonitis, eight patients with idiopathic lung fibrosis, and six healthy controls by immunodiffusion and immunofluorescent testing of personal spore samples. The new technique of personal spore sampling with the Burkard personal volumetric air sampler and indirect immunofluorescent test for detection of spore-specific IgG and IgM confirmed that five patients with hypersensitivity pneumonitis and four with lung fibrosis were actually exposed and sensitized to moulds. Personal spore sampling and subsequent immunofluorescent tests represent sensitive tools for detection of individual mould sensitization and air quality control. PMID- 1910267 TI - Postnatal development of forebrain regions in the autoimmune NZB-mouse. A model for degeneration in neuronal systems. AB - NZB-mice are known to have impaired cognitive functions. The aim of the present study is the analysis of the volume growth of different brain regions in NZB/NBOM mice, because the functional impairment increases postnatally. The regions analysed include brain structures which are important for learning and memory functions. The comparison between NZB-mice and controls (CFW- and Balb/c-mice) shows that the hippocampal volume in NZB-mice is larger than in controls. However, ectopic neurons are found in the dentate gyrus of NZB-mice, indicating a changed connectivity in this region. The septum and the amygdala show no difference in volume in NZB-mice compared to controls. The adult volume of the entorhinal cortex of the NZB-mice is the smallest of the three strains. The development of this brain region is characterized by an overshooting growth in all strains. The caudate-putamen complex and the globus pallidus of NZB-mice undergo a reduction in volume during the postnatal period. This is not found in the controls. An overshooting growth is seen in the mamillary bodies of the three strains, and in the anterior thalamic nucleus of NZB-mice. However, only the NZB mice show a prolonged reduction of the volume of the mamillary bodies, which is not finished during the observed time period. Both regions are important relay stations in the Papez-circuit, a neuronal system associated with learning and memory functions. The prolonged postnatal reduction in volume of the mamillary bodies and the anterior thalamic nucleus of NZB-mice may be the structural correlate of the impaired cognition and memory in this strain. PMID- 1910268 TI - Human seminal fibrinolytic activity: specific determinations of tissue plasminogen activator and urokinase. AB - The determination of total fibrinolytic activity of ejaculates was realized by fibrin plate method. For the same seminal samples, tissue plasminogen activator (t-PA), urinary plasminogen activator (uPA) antigens and uPA activity were specifically quantified. The seminal values were fifty times higher than in the blood for t-PA and fifteen times for uPA. There was no correlation between the both levels but from split ejaculates measurements a higher concentration was observed in all first fractions. By zymography assays, it was shown that seminal plasminogen activators are under active forms. The lack of proUrokinase in semen was also demonstrated. PMID- 1910269 TI - Use of adult male bonnet monkeys (Macaca radiata) for testing the biological activity of gonadotropin releasing hormone and its analogues. AB - The effect of injecting agonistic and antagonistic analogues of gonadotropin releasing hormone analogues on serum testosterone levels was checked in adult and immature male bonnet monkeys. Of the agonistic analogues Buserelin, Ovurelin and D-Phe6 Gln8 GnRH were found to be most potent in increasing serum testosterone levels in the adult male bonnet monkeys. While 27-month-old monkeys responded well to des Gly10 GnRH, only marginal response was observed in the case of 15 month-old monkeys. Studies carried out with Ovurelin indicated that it was not effective in causing desensitization in adult monkeys. The antagonistic analogue was effective in blocking nocturnal surge of serum testosterone. Based on these studies it is suggested the adult male bonnet monkeys can be effectively used for testing the activity of GnRH analogues. PMID- 1910271 TI - Capnography: never forget the false-positives! PMID- 1910270 TI - A comparison of cerebral blood flow reactivity to CO2 during halothane versus isoflurane anesthesia for carotid endarterectomy. AB - The effects of isoflurane or halothane on cerebral blood flow (CBF) reactivity to changes in arterial carbon dioxide tension (PaCO2) during carotid endarterectomy were compared using the intravenous method of 133Xe-CBF determination. Patients, aged 65 +/- 3 yr (mean +/- SE), received O2 and N2O (1:1) and either 0.75% isoflurane (n = 7) or 0.5% halothane (n = 7). Patient demographic and clinical data were similar for both groups and followed the expected strata of patients with ischemic cerebrovascular disease. Measurements were made during the period of temporary bypass shunting. In the isoflurane group, increasing PaCO2 from 33.3 +/- 1.4 to 43.4 +/- 1.3 mm Hg resulted in a significant (P less than 0.05) increase in CBF from 21 +/- 1 to 35 +/- 4 mL.100 g-1.min-1. In the halothane group, increasing PaCO2 from 31.1 +/- 1 to 39.4 +/- 1.6 mm Hg resulted in a significant increase in CBF from 26 +/- 3 to 37 +/- 3 mL.100 g-1.min-1. Mean CBF reactivity to changes in PaCO2 (mL.100 g-1.min-1.mm Hg-1) was 1.74 +/- 0.39 for isoflurane and 1.78 +/- 0.4 for halothane (not significant), corresponding to a relative change of 4.8% +/- 0.8% and 5.2% +/- 1.3% per mm Hg, respectively. There is no significant difference between halothane and isoflurane in their effects on CO2 reactivity in the mildly hypocapnic to normocapnic range. PMID- 1910272 TI - [The functional state of the lungs and its changes in response to nitrates in patients in the immediate period following aortocoronary bypass]. PMID- 1910273 TI - Effects of HIV infection on pregnancy. A clinical and immunologic evaluation. AB - To understand better the effects of HIV infection on pregnancy, a group of 16 HIV seropositive pregnant patients was evaluated prospectively. Complications and results of pregnancy in these individuals were compared with those of 1,906 births at Charity Hospital, New Orleans during the time of the study. A subgroup of five patients underwent immunologic testing prenatally and postpartum. Thirty one percent of HIV seropositive subjects had premature labor and low birth weight infants. Only 3.1% of the controls had premature labor and low birth weight infants (p less than or equal to .05). The percentage of C-sections was lower in the study group (12.5% versus 31.3%, p less than .10). All patients remained free of HIV-related disease through the postpartum period. Mean CD4 percentages were lower postpartum (21.9 +/- 3.4) than prepartum (45.1 +/- 6.7) in all five patients studied, although proliferative responses to the mitogens phytohemagglutinin and pokeweed were unchanged during the study period. One of the five seropositive patients who underwent immunologic testing with a CD4:CD8 ratio of less than 1.0 prepartum, had a progressive fall in CD4 percentages from 30% to 11% during the course of the study. HIV-I core antigen was not detected in the serum of any of the five patients during pregnancy or postpartum. Thus, HIV-I infection influenced both the course and outcome of pregnancy in the population studied. Further studies are indicated to assess the effects of pregnancy on the progression of HIV-related immunodeficiency in this population. PMID- 1910274 TI - Neuritic pathology and dementia in Alzheimer's disease. AB - Previous studies of Alzheimer's disease (AD) have correlated the severity of dementia with either the number of senile plaques or neurofibrillary tangles. We used antibodies raised against amyloid beta/A4 protein of senile plaque cores and tau protein as well as thioflavine S and the Campbell-Switzer modification of the Hicks silver method to examine the hippocampal formation and five neocortical regions from 22 nondemented elderly control subjects and 34 demented patients with cerebral senile plaques and neurofibrillary tangles, without complicating disease processes. Ten control subjects (46%) had no beta/A4 protein deposition. Twelve control subjects (54%) had widespread beta/A4 protein deposition but no neocortical neuritic pathology. Of the 34 patients with AD-type changes, 27 (79%) had widespread senile plaques and neurofibrillary tangles, while 7 (21%) had neocortical senile plaques with few neurofibrillary tangles. All demented patients had widespread beta/A4 protein deposition and neocortical tau immunoreactive, Hicks silver-positive dystrophic neurites. The neurites were found both free in the neuropil as well as surrounding senile plaques. Quantitative analysis showed that dystrophic neurites were significantly increased in patients with AD compared with control subjects and the number of dystrophic neurites and neurofibrillary tangles correlated with the clinical severity of dementia. Widespread cerebral beta/A4 protein deposition may be necessary but by itself is insufficient for the development of dementia in AD. PMID- 1910275 TI - Normal aging of the nervous system. PMID- 1910276 TI - Iatrogenic amyloidotic apoplexy. PMID- 1910277 TI - Effect of Medicare prospective payment system on a home health agency: changes in patient population and services provided. AB - Data from a large home health agency was retrospectively reviewed to determine the effect of Medicare's Diagnosis Related Group (DRG) payment system on posthospital care. Variables included demographics, diagnoses, functional ability, frequency and type of services provided, and discharge status. An increase in the provision of rehabilitation and nursing services provided in the post-DRG population was found. No negative effects on patient outcomes, such as increases in emergency room visits, rehospitalization, or death, were found. PMID- 1910278 TI - Family members' perceptions of care of institutionalized patients with Alzheimer's disease. PMID- 1910279 TI - Purification and characterization of an epoxide hydrolase from the peroxisomal fraction of mouse liver. AB - Epoxide hydrolase (EH) activity has been reported to occur in most subcellular fractions of mouse liver. The EHs in the microsomal and cytosolic fractions have been purified and characterized; however, the nature of the EH(s) in the peroxisomal fraction is not known. Therefore an EH, pEH, was purified from the solubilized 12,000g fraction, which contain peroxisomes. Previous studies have demonstrated that the EH activity in this crude solubilized 12,000g fraction resides mostly in the peroxisomes. Thus the crude 12,000g pellet from mouse liver, free from cytosolic contamination, was sonicated to obtain a 105,000g soluble fraction containing 80% of the original EH activity in this fraction. The pEH was purified, using trans-stilbene oxide (TSO) as substrate, by a combination of affinity and hydroxyapatite chromatography. The purified pEH had a native molecular weight of 57 kDa, a molecular weight of 59 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and a pI of 5.7. The purified pEH was observed to be immunologically similar to the cytosolic EH (cEH). The kinetics of hydrolysis of TSO, however, were slightly different. Lineweaver-Burk plots for the inhibition of pEH suggest a probable noncompetitive, mixed-type inhibition. The purified pEH thus appears to be very similar to the cEH. There are minor differences between the purified cEH and pEH, particularly in the kinetic parameters. However, these minor differences are insignificant. These results demonstrate that the cEH and pEH are substantially similar, if not identical. PMID- 1910280 TI - A single-step separation of the one- and two-chain forms of tissue plasminogen activator. AB - Preparations of one-chain tissue plasminogen activator (tPA), usually a mixture of 65- and 63-kDa differentially glycosylated forms, contain variable amounts of two-chain tPA. There is no effective procedure currently available for removal of the two-chain contaminant from one-chain tPA preparations. In this report, affinity chromatography on benzamidine-Sepharose was investigated for the separation of two-chain from one-chain tPA. Activase, a preparation of recombinant tPA containing 80% one-chain tPA, a mixture of 65- and 63-kDa variants, and 20% two-chain tPA, was applied to a column of benzamidine Sepharose, equilibrated with 1 M ammonium bicarbonate. Under this condition, both one-chain and two-chain forms of tPA were adsorbed by the column. Addition of 0.1 M arginine to the equilibration buffer led to elution of two-peaks, corresponding to the 65- and 63-kDa variants of one-chain tPA. Two-chain tPA remained bound to the column, but could be eluted with sodium acetate buffer, pH 4.0, containing 0.1 M arginine. The present procedure allows rapid and effective removal of two chain tPA with concomitant separation of 65- and 63-kDa one-chain glycoforms from preparations of one-chain tPA. Kinetic analysis for the hydrolysis of D-Ile-Pro Arg-p-nitroanilide (S-2288) by the highly purified molecular forms of tPA suggests that 63-kDa one-chain tPA possesses 30% higher catalytic efficiency than the 65-kDa variant, while two-chain tPA is 9- or 12-fold more efficient than 63- or 65-kDa one-chain tPA, respectively. PMID- 1910281 TI - Modulation of the tight binding of carboxyarabinitol 1,5-bisphosphate to the large subunit of ribulose 1,5-bisphosphate carboxylase/oxygenase. AB - The large subunit (L) of ribulose 1,5-bisphosphate carboxylase/oxygenase (rubisco) from Synechococcus PCC 6301 was expressed in Escherichia coli, purified as the octamer L8, and analyzed for its ability to tightly bind the transition state analog, 2-carboxyarabinitol 1,5-bisphosphate (CABP). [14C]CABP remained tightly bound to L8 after challenging with [12C]CABP and gel filtration, indicating that L8 alone without the small subunit (S) could tightly bind CABP. Binding of CABP to L8 induced a shift in the gel filtration profile due to apparent aggregation of L8. Aggregation did not occur with the L8S8-CABP complex nor with L8-CABP in the presence of 150 mM MgCl2. If ionic strength was increased with either KCl or MgCl2 during or after the binding of [14C]CABP to L8, [14C]CABP in the complex exchanged with [12C]CABP and was lost from the protein. Ionic strength strongly affected the rate constant (k4) for [14C]CABP dissociation from the L8-[14C]CABP complex, but had little effect on k4 for the L8S8-CABP complex. The differences in CABP binding characteristics between the L8 CABP and L8S8-CABP complexes demonstrate that S is intimately involved in maintaining the stability of the tight binding of CABP to the active site. These are the same interactions stabilizing the intermediate, 3-keto-2 carboxyarabinitol 1,5-bisphosphate, to native rubisco during CO2 fixation. PMID- 1910282 TI - In vitro metabolism of juvenile hormone III and juvenile hormone III bisepoxide by Drosophila melanogaster and mammalian cytosolic epoxide hydrolase. AB - In vitro metabolism of juvenile hormone III (JH III) and juvenile hormone III bisepoxide was investigated using purified mouse liver cytosolic epoxide hydrolase (cEH) and cell fractions from Drosophila melanogaster. JH III was metabolized faster than JH III bisepoxide by epoxide hydrolase activity in D. melanogaster cell fractions and by cEH. After incubation with JH III bisepoxide, all cell fractions and cEH produced epoxy-diol, cis- and trans-tetrahydrofuran diols, and tetraol as metabolites. An increase in the concentration of cEH resulted in an increase in the proportion of tetraol as a JH III bisepoxide metabolite but this trend was not observed in the D. melanogaster cell fractions. Differences between cell fractions in the metabolism of JH III and JH III bisepoxide suggests the presence of juvenile hormone epoxide hydrolase isozymes. PMID- 1910283 TI - Nitrate transport and its regulation by O2 in Pseudomonas aeruginosa. AB - Pseudomonas aeruginosa is an obligate respirer which can utilize nitrate as a terminal electron acceptor under anaerobic conditions (denitrification). Immediate, transient regulation of nitrate respiration is mediated by oxygen through the inhibition of nitrate uptake. In order to gain an understanding of the bioenergetics of nitrate transport and its regulation by oxygen, the effects of various metabolic inhibitors on the uptake process and on oxygen regulation were investigated. Nitrate uptake was stimulated by the protonophores carbonyl cyanide m-chlorophenylhydrazone and 2,4-dinitrophenol, indicating that nitrate uptake is not strictly energized by, but may be affected by the proton motive force. Oxygen regulation of nitrate uptake might in part be through redox sensitive thiol groups since N-ethylmaleimide at high concentrations decreased the rate of nitrate transport. Cells grown with tungstate (deficient in nitrate reductase activity) and azide-treated cells transported nitrate at significantly lower rates than untreated cells, indicating that physiological rates of nitrate transport are dependent on nitrate reduction. Furthermore, tungstate grown cells transported nitrate only in the presence of nitrite, lending support to the nitrate/nitrite antiport model for transport. Oxygen regulation of nitrate transport was relieved (10% that of typical anaerobic rates) by the cytochrome oxygen reductase inhibitors carbon monoxide and cyanide. PMID- 1910284 TI - The interaction of ferredoxin and glutamate synthase: cross-linking and immunological studies. AB - The water-soluble carbodiimide, N-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) serves as an effective reagent for cross-linking spinach leaf ferredoxin and the ferredoxin-dependent spinach leaf enzyme, glutamate synthase. The cross linked complex was functional in the absence of added ferredoxin, suggesting that ferredoxin is cross-linked to glutamate synthase at the physiological binding site on the enzyme for this iron-sulfur protein electron donor. The ferredoxin:glutamate synthase stoichiometry of the cross-linked complex was estimated to be 2:1. The absorbance spectrum of the oxidized, cross-linked complex was very similar to that of an electrostatically stabilized, noncovalent, 2:1 complex of the two proteins. An antibody raised against spinach NADP+ reductase, which recognizes a ferredoxin-binding site on glutamate synthase, does not recognize the cross-linked ferredoxin-glutamate synthase complex. This implies that the ferredoxin-binding sites on the two enzymes are structurally similar enough so that an antibody raised against one of these ferredoxin dependent enzymes recognizes an epitope at the ferredoxin-binding site of the second enzyme. Cross-linking of ferredoxin to its binding site on glutamate synthase renders this epitope inaccessible to the antibody. PMID- 1910285 TI - pH-sensitive control of arginase by Mn(II) ions at submicromolar concentrations. AB - The manganese dependence of arginase was reinvestigated with extracts of mouse liver to see whether more physiological properties were displayed than have been reported for the purified enzyme. In a preincubation with Mn(II) ions at 37 degrees C the enzyme underwent a slow and reversible activation. At least 90-95% of the activation achieved was dependent on Mn2+. However, no Mn2+ was required for catalytic activity in the assay. The activation showed little dependence upon pH over the range 6.5-9.5, whereas the catalytic activity increased 12-fold in apparent accord with the titration curve of an ionizable group of pKa 7.9. The Mn2+ dependence of arginase activation obeyed Michaelis-Menten kinetics, with Kd varying from 0.3 microM at pH 6.8 to 0.08 microns at pH 7.7. Free Mn2+ concentrations were established in these assays with a trimethylenediaminetetraacetate-Mn buffer. Vmax increased about three-fold over this range. The calculated arginase activity at 0.05 microM Mn2+ increases about nine-fold over this physiological pH range. An enzyme model is proposed to explain these findings. The activity of arginase at "physiological" [Mn2+] and the pronounced pH dependence conferred upon it are consistent with a recently revised role for the urea cycle in the control of bicarbonate and pH in the body. It appears possible that arginase loses Mn2+ sensitivity during the usual purification. PMID- 1910286 TI - Copurification of bovine milk xanthine oxidase and immunoglobulin. AB - Xanthine oxidase, isolated from bovine milk, exhibited an A280:A450 nm ratio of 5.0. This ratio is reported to be indicative of highly purified enzyme preparations. Serum from a rabbit hyperimmunized against this enzyme fraction exhibited two precipitation lines when incubated with the protein in agarose double diffusion plates. Serum albumin, beta-lactoglobulin, alpha-lactalbumin, lactoferrin, casein, chymosin, and immunoglobulin were tested for reactivity. The second antigen was identified as bovine immunoglobulin. Commercial preparations of xanthine oxidase also contained immunoglobulin as a contaminant. IgG and IgA were present in Sigma (Grade III) fractions and IgM was identified in Boehringer Mannheim preparations. Immunofluorescent studies indicated that xanthine oxidase antiserum reacted with the capillary endothelium of bovine heart. Absorption of this antiserum with bovine IgG abrogated this reaction. These findings may explain apparent discrepancies between reported immunohistological association of xanthine oxidase in heart capillary endothelial cells and the absence of detectable enzymatic activity. PMID- 1910287 TI - Pyruvate:NADP+ oxidoreductase from Euglena gracilis: limited proteolysis of the enzyme with trypsin. AB - Pyruvate:NADP+ oxidoreductase from Euglena gracilis, a homodimeric protein with a molecular weight of 309 kDa, is an iron-sulfur flavoenzyme that contains thiamin pyrophosphate (TPP). The functional structure of the enzyme was studied by a limited proteolysis experiment using trypsin. The evidence obtained shows that the enzyme consists of two functional domains, one of which contains an iron sulfur cluster, which can be isolated as a homodimeric fragment of approximately 220 kDa by proteolysis. The other domain that contains FAD is released as a monomeric fragment of approximately 55 kDa. The pyruvate dehydrogenase reaction is still catalyzed by the large fragment when NADP+ is substituted by methyl viologen, while the small fragment retains a diaphorase-like electron-transfer activity from NADPH to MV. It is thus shown that pyruvate is oxidized in a CoA dependent reaction to form CO2 and acetyl-CoA in the iron-sulfur domain, and that the two electrons formed are transferred to the FAD domain in which NADP+ is reduced. TPP is considered to be associated in the iron-sulfur domain. The NH2 terminal sequences of the enzyme and its proteolytic fragments reveal that the iron-sulfur domain occurs in the NH2-terminal side of the enzyme. For elucidation of the O2 instability of the enzyme, limited proteolysis was attempted in air. The tryptic fragment derived from the iron-sulfur domain, similar to the native enzyme, appears to be inactivated by direct contact with O2. In contrast, the FAD domain, when separated from the other domain, is quite stable in air, although the diaphorase activity decays when the native enzyme is exposed to O2. PMID- 1910288 TI - Localization and characterization of phospholipase A2 in mouse mammary gland derived cells. AB - Phospholipase A2 (PLA2) can participate in the regulation of eicosanoid biosynthesis via PLA2-mediated control of the release of arachidonic acid from phospholipids. Arachidonoyl-hydrolyzing PLA2s were examined in cells from normal mouse mammary glands and mammary carcinomas. Tumor-derived cells exhibited significant PLA2 activity(ies) with arachidonoyl containing phosphatidylcholine and phosphatidylethanolamine as substrates in cell-free assays. In contrast, arachidonoyl containing phosphatidylinositol was a poor substrate. When phosphatidylcholines with varying sn-2 fatty acyl groups were tested as substrates, activity was highest with the arachidonoyl containing lipid. The pH profiles for hydrolysis of phosphatidylcholine and phosphatidylethanolamine differed; all other aspects of PLA2-mediated hydrolysis of these two substrates were similar including a Ca2+ requirement for activity. Moreover, Ca2+ affected the subcellular localization of the enzyme activity. Activity was predominately in the supernatant fraction when cells were harvested in an EGTA (ethylene glycol bis(beta-aminoethylether)-N,N,N',N'-tetraacetic acid) containing buffer and largely in the particulate fraction when cells were harvested in a buffer containing free Ca2+. The localization of activity could be modulated from the supernatant fraction to the particulate fraction by recentrifugation in the presence of Ca2+. Normal gland-derived cells contained a PLA2 activity with properties similar to those of the tumor-derived cells. There was a significant difference in the level of activity in the normal versus tumor cells, the normal gland-derived cells had less than half the PLA2 activity of the carcinoma-derived cells. PMID- 1910289 TI - Purification and characterization of large and small subunits of ribulose 1,5 bisphosphate carboxylase expressed separately in Escherichia coli. AB - Procedures were developed for 95 and 80% purification to homogeneity of the large subunit (L) and small subunit (S) of ribulose 1,5-bisphosphate carboxylase/oxygenase (L8S8) from Synechococcus PCC 6301, each expressed separately in Escherichia coli. Purified L had a low specific activity in the absence of S (0.075 mumol CO2 fixed/mg holoenzyme/min). Following elution on a Pharmacia Superose 6 or 12 gel filtration column, 50% of the purified L appeared as the octamer, L8. The rest was in equilibrium with lower polymeric species and/or was retained on the column. Large and small subunits assembled rapidly into the L8S8 holoenzyme that had high specific activities, 6.2 and 3.1 mumol CO2 fixed/mg holoenzyme/min for the homologous Synechococcus L8S8 and the hybrid Synechococcus L-pea S L8S8, respectively. The CO2 dependence for carbamylation of L8 was compared to that of L8S8 as a function of pH and CO2 concentration. The pH dependence indicated an apparent pKa for L8 of 8.28 and for L8S8 of 8.15, suggesting that S may influence the pKa of the lysine involved in carbamylation. The Kact for CO2 at pH 8.4 were similar for L8 (13.5 microM) and L8S8 (15.5 microM). L8 bound 2-[14C]carboxy-D-arabinitol 1,5-bisphosphate (CABP) tightly so that most of the bound [14C]CABP survived gel filtration. A major amount of the L8-[14C]CABP complex appeared as larger polymeric aggregates when eluted in the presence of E. coli protein. PMID- 1910290 TI - Modulation of fibroblast motility by a cytosolic extract of Cyanobacteria. AB - Proliferation and migratory behavior of L929 murine fibroblasts were shown to be modified in the presence of a cytosolic extract of Phormidium sp. (Cyanobacteria). The addition of Phormidium extract to the growth medium (Dulbecco's modified Eagle's medium) supplemented with 0.5% newborn calf serum increased cell proliferation. The effect was shown to be cell line specific. A quantitative analysis performed according to De Laat, Tertoolen, and Bluemink (1981, Eur. J. Cell Biol., 23, 273-279), showed that Phormidium extract was a potential aggregative effector for fibroblasts. Heating (100 degrees C, 4 min) inactivated the clustering effect of the extract, but the effect on cell proliferation was retained. A video analysis of cells after divisions showed that the extract activated cell migration in the same way as 5% serum did during the first 24 h of treatment. Between 24 and 48 h of treatment, cell migration in the presence of the extract was inhibited when compared to migration in 0.5 or 5% serum. We have shown that Phormidium extract may contain two or three kinds of effectors which acted as exogenous growth factors (allowing attachment and proliferation) and as modulator(s) of the cell migratory behavior (activator of migration in early times of the growth and inhibitor later). PMID- 1910291 TI - Transforming growth factor-beta 1 stimulates synthesis of proteoglycan aggregates in calf articular cartilage organ cultures. AB - Previous work showed that transforming growth factor-beta 1 (TGF-beta 1), added alone to bovine cartilage organ cultures, stimulated [35S]sulfate incorporation into macromolecular material but did not investigate the fidelity of the stimulated system to maintain synthesis of cartilage-type proteoglycans. This paper provides evidence that chondrocytes synthesize the appropriate proteoglycan matrix under TGF-beta 1 stimulation: (i) there is a coordinated increase in hyaluronic acid and proteoglycan monomer synthesis, (ii) link-stable proteoglycan aggregates are assembled, (ii) the hybrid chondroitin sulfate/keratan sulfate monomeric species is synthesized, and (iv) there is an increase in protein core synthesis. Some variation in glycosylation patterns was observed when proteoglycans synthesized under TGF-beta 1 stimulation were compared to those synthesized under basal conditions. Thus comparing TGF-beta 1 to basal samples respectively, the monomers were larger (Kav on Sepharose CL-2B = 0.29 vs 0.41), the chondroitin sulfate chains were longer by approximately 3.5 kDa, the percentage of total glycosaminoglycan in keratan sulfate increased slightly from approximately 4% (basal) to approximately 6%, and the unsulfated disaccharide decreased from 28% (basal) to 12%. All of these variations are in the direction of a more anionic proteoglycan. Since the ability of proteoglycans to confer resiliency to the cartilage matrix is directly related to their anionic nature, these changes would presumably have a beneficial effect on tissue function. PMID- 1910292 TI - Inhibition of ADP-induced platelet shape change and aggregation by o phthalaldehyde: evidence for covalent modification of cysteine and lysine residues. AB - Platelets play a major role in the hemostatic process following vascular injury. Chemical modification of cysteine and/or lysine residues in platelet proteins has been shown to cause loss of platelet aggregation induced by diverse agonists; however, these investigations have not addressed the identity of the specific proteins affected. o-Phthalaldehyde (OPTH) is a unique chemical modification reagent that forms and permits the identification of fluorescent isoindole derivatives with proteins by covalently and simultaneously modifying closely spaced cysteine and lysine residues. We found that OPTH inhibited platelet aggregation induced by ADP, collagen, and U46619 (an analog of prostaglandin H2), but had minimal effect on platelet aggregation induced by thrombin, plasmin, chymotrypsin, A23187 (a calcium ionophore), PMA (phorbol 12-myristate 13 acetate), and PMA + A23187. Since platelet aggregation induced by ADP, collagen, and U46619 has been shown to involve binding of endogenous or exogenous ADP to the platelet receptor, our further studies focused on platelet aggregation induced by ADP. OPTH inhibited ADP-induced shape change and aggregation in a concentration-dependent manner. The second-order rate constant for the inhibition of ADP-induced platelet shape change (Ksc = 1.0 X 10(3) M-1 s-1) was lower than that for aggregation (Kagg = 5.4 X 10(3) M-1 s-1). Fluorescence excitation and emission spectra of OPTH-platelet adduct exhibited maxima at 346 and 437 nm, respectively, consistent with the formation of an isoindole derivative(s). The nonpenetrating thiol-specific reagent, p-chloromercuribenzenesulfonate (pCMBS) (0.8 mM), is known to block the inhibition of stimulated adenylate cyclase induced by ADP but not the ADP-induced platelet shape change. The inhibition of ADP-induced platelet shape change (Ksc = 1.5 X 10(3) M-1 s-1) by OPTH was not affected by pCMBS. OPTH, at concentrations (15-50 microM) that inhibited ADP induced platelet aggregation and shape change did not raise the intracellular levels of adenosine cyclic 3',5'-monophosphate (cAMP) in platelets nor did it impair the ability of iloprost (a stable analog of prostaglandin I2) to raise the platelet cAMP level. Thus, OPTH under these conditions did not interact with platelet adenylate cyclase. 5'-p-fluorosulfonylbenzoyladenosine (FSBA) has been previously shown to inhibit ADP-induced platelet shape change and aggregation by covalently modifying aggregin (Mr = 100 kDa), a putative ADP receptor on platelet surface.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1910293 TI - Verotoxin-resistant cell clones are deficient in the glycolipid globotriosylceramide: differential basis of phenotype. AB - Escherichia coli-derived verotoxin is an extremely toxic protein and is highly selective toward certain primate cells. Two susceptible cell lines are the Daudi cell line (human Burkitt lymphoma) and the Vero cell line (Green African monkey kidney). Both of these cell lines contain significant levels of the verotoxin binding glycolipid globotriosylceramide (Gb3) (1 nmol/10(7) cells and 3 nmol/10(6) cells, respectively). A clone was selected from the Vero cell line for resistance to Verotoxin 2, while a mutant from the Daudi cell line was selected for resistance to Verotoxin 1. Both were found to be deficient in globotriosylceramide with a corresponding increase in the precursor glycolipid lactosylceramide. Cell free assay of alpha-galactosyltransferase activity revealed that the Vero cell clone (VRP) contained significantly reduced enzyme activity, whereas in the case of the Daudi mutant (VT20), no significant decrease in activity was noted in vitro. These observations suggest a complex regulation of Gb3 biosynthesis which is considered in relation to P blood group antigen expression. PMID- 1910294 TI - Purification and immunological characterization of a novel cytochrome P450 from C3H/10T1/2 cells. AB - The major polycyclic aromatic hydrocarbon-metabolizing cytochrome P450 in the mouse embryo fibroblast-derived C3H/10T1/2 CL8 cell line (P450-EF) has been partially purified from benz[a]anthracene (BA)-induced 10T1/2 cells (40 pmol P450/mg). The purification of P450-EF was carried out by sequential chromatography of solubilized microsomes over hydrophobic aminohexyl-Sepharose 4B, anion exchange DE-52 cellulose, and cation exchange carboxymethyl trisacryl columns. The final preparation (1700 pmol/mg) appeared as a single major 55-kDa band by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Reconstitution of detergent-free partially purified P450-EF yielded a relatively high turnover for 7,12-dimethylbenz[a]anthracene (DMBA) metabolism (5.4 nmol/nmol/min). Polyclonal antibodies to purified P450-EF (anti-P450-EF), raised in, respectively, rabbit and chicken, detected a single 55-kDa band in 10T1/2 cell microsomes that was highly inducible by BA (approximately 20-fold) and TCDD (approximately 5-fold). Rabbit anti-P450-EF was much more effective than the corresponding chicken antibody at binding denatured P450-EF protein on Western blots. Conversely, only the chicken antibody was effective at inhibiting DMBA metabolism catalyzed by microsomal P450-EF. This antibody did not inhibit P450IA1 mediated DMBA metabolism. Rabbit anti-P450-EF recognized very weakly (less than 1% of homologous protein response) pure P450IA1, IIB1, IIC7, IIE1, and IIIA1 proteins on Western blots but exhibited substantial cross-reactivity (approximately 10%) with pure P450IIA1 and very strong cross-reactivity (approximately 75%) with a hormonally regulated rat adrenal P450. Polyclonal antibodies to several major P450 subfamilies either did not recognize P450-EF (anti-P450IA, IIB, and IIC) or recognized it very weakly (anti-P450IIA1). P450-EF is probably distantly related to the P450IIA subfamily and may belong to a new P450 subfamily. PMID- 1910295 TI - Reduction of a disulfide bond of thrombospondin in the supernatant solution of activated platelets. AB - Incubation of the material secreted by activated platelets leads to the formation of disulfide-linked dimers and multimers of one of the proteins, thrombospondin. To determine whether these complexes formed as a result of thiol-disulfide exchange (no change in the number of thiols) or of oxidation of thiols (a decrease in the number of thiols), the number of thiols in TSP was measured during formation of multimers. The number of thiols increased from about 3/mol to 4.8/mol. The half-time for the disappearance of monomers of thrombospondin was fourfold greater than the half-time for appearance of new thiols. The appearance of new thiols, as well as the formation of multimers, was inhibited by Ca2+. The appearance of new thiols was reversible; addition of Ca2+ reversed the process, and at pH 8, but not at pH 6 or 7, the appearance of new thiols spontaneously reversed. No new thiols formed during incubation of partially purified thrombospondin or after the supernatant solution had been treated with activated thiol-Sepharose to remove reactive thiol compounds. It is concluded that thrombospondin has a disulfide bond that is unstable in the absence of Ca2+. It can be attacked by a thiol of another molecule of thrombospondin to form disulfide-linked multimers, by a thiol of the same molecule of thrombospondin to generate isomerization of disulfide bonds or, as observed in this study, by another secreted thiol compound to give a mixed disulfide and a new thiol. PMID- 1910296 TI - New inhibitors of aldose reductase: anti-oximes of aromatic aldehydes. AB - Aldose reductase is an NADPH-dependent enzyme which catalyzes the reduction of glucose to sorbitol. Specific potent inhibitors of aldose reductase are of potential pharmacological use because elevated levels of sorbitol produced by this enzyme in lens, peripheral nerve, retina, and renal glomeruli may be responsible for the pathogenesis associated with chronic diabetes. These inhibitors could also serve as probes of the mechanism of action of aldose reductase. anti-Oximes of aromatic aldehydes (e.g., benzaldoxime and 4 fluorobenzaldoxime) have proved to be effective inhibitors of aldose reductase rivaling pharmacological agents currently used to inhibit this enzyme in vivo. The kinetic patterns of inhibition in which benzyl alcohol is used as the oxidizable substrate suggest that the inhibition is due to the formation of a stable ternary complex composed of aldose reductase, NADP+, and the anti-oxime. Analogus ternary complexes are formed at the active site of horse liver alcohol dehydrogenase which is also inhibited by anti-oximes of efficient substrates. PMID- 1910297 TI - The involvement of catalase in alcohol metabolism in Drosophila melanogaster larvae. AB - The involvement of catalase (H2O2:H2O2 oxidoreductase, EC 1.11.1.6) in the metabolism of alcohols was investigated by comparing Drosophila melanogaster larvae in which catalase was inhibited by dietary 3-amino-1,2,4-triazole (3AT) to larvae fed a diet without 3AT. 3AT inhibited up to 80% of the catalase activity with concordant small increases in the in vitro activities of sn-glycerol-3 phosphate dehydrogenase, fumarase, and malic enzyme, but with a 16% reduction in the in vivo incorporation of label from [14C]glucose into lipid. When the catalase activity was inhibited to different degrees in ADH-null larvae, there was a simple linear correlation between the catalase activity and flux from [14C]ethanol into lipid. By feeding alcohols simultaneously with 3AT, ethanol and methanol were shown to react efficiently with catalase in wild-type larvae at moderately low dietary concentrations. Drosophila catalase did not react with other longer chain alcohols. Catalase apparently represents a minor pathway for ethanol degradation in D. melanogaster larvae, but it may be an important route for methanol elimination from D. melanogaster larvae. PMID- 1910298 TI - Ureidoglycolate amidohydrolase from developing French bean fruits (Phaseolus vulgaris [L.].). AB - Ureidoglycolate is an intermediate of allantoin catabolism in ureide-transporting legumes. This report describes the first purification of ureidoglycolate degrading activity (UGDA) from plant tissue in which the enzyme has been separated from urease. The enzyme from developing fruits of Phaseolus vulgaris has been purified 48-fold to give a preparation free of allantoinase and urease activity. UGDA was inhibited by EDTA while the Vmax was increased in the presence of Mn2+. The Km values for ureidoglycolate in the presence and the absence of Mn2+ were 2.0 and 5.4 mM, respectively. In the absence of Mn2+ UGDA was heat labile at 40 degrees C, but in the presence of Mn2+ the activity was stable up to temperatures of 60 degrees C. The Mr of UGDA was determined to be 300,000 by gel filtration chromatography and the pH optimum ranged from pH 7.0 to 8.5. Ammonia was determined to be the nitrogen-containing product of UGDA by a microdiffusion assay. This enzyme should therefore be described as ureidoglycolate amidohydrolase. The activity was shown to be associated with peroxisomes by fractionation of a crude extract on a sucrose density gradient. The products of ureidoglycolate degradation are glyoxylate, ammonia, and presumably carbon dioxide, which can be readily utilized by pathways of metabolism that are known to be present in this organelle. PMID- 1910299 TI - Progesterone binding in a clinical isolate of Pseudomonas aeruginosa. AB - We have undertaken the characterization of progestin binding component(s) in the cytosol prepared from Pseudomonas aeruginosa isolated from an immunocompromised patient. Incubation of P. aeruginosa cytosol aliquots at 0 degrees C with 20 nM [3H]R5020 (a synthetic progestin) revealed the presence of saturable binding. The [3H]R5020 binding reached an equilibrium after 1 h at 0 degrees C and showed saturation at 30-50 nM with a Kd value of 7.7 nM. At 0 degrees C, beta mercaptoethanol increased the [3H]R5020 binding by 20% but sodium molybdate had no effect. The [3H]R5020-macromolecular complex was stable for up to 4 h at 37 degrees C. Steroid binding specificity analysis revealed that [3H]R5020 binding could be eliminated in the presence of 2 microM progesterone, estradiol, or dihydrotestosterone but that the synthetic glucocorticoid, triamcinolone acetonide, did not compete. Postlabeling of the cytosol fractions obtained after 10-30% glycerol gradient analysis demonstrated association of the radioactivity with a molecule that sedimented as a 6-8 S protease-sensitive moiety which was unaltered in the presence of RNase or DNase. When cells were grown in the presence of 100 nM progesterone, a 50% inhibition in the number of resulting colonies was observed. In addition to its evolutionary significance, the presence of this steroid binding molecule suggests a potential in the endocrine manipulation in the treatment of infections caused by P. aeruginosa. PMID- 1910300 TI - Differential effects of insulin, epinephrine, and glucagon on rat hepatocyte mitochondrial activity. AB - Oxidation of [2,3-14C]succinate carbons in the mitochondrial Krebs cycle was used as a probe to investigate the effects of insulin, epinephrine, glucagon, and 2,4 dinitrophenol (2,4-DNP) on isolated rat hepatocytes. Epinephrine, glucagon, and 2,4-DNP had a far greater stimulatory effect on 14CO2 formation from [2,3 14C]succinate than insulin. Unlike insulin, epinephrine and glucagon had no significant effect on the anabolic utilization of succinate carbons for protein synthesis. Our results suggest that although epinephrine, glucagon, and 2,4-DNP enhance the movement of tracer carbons through the Krebs cycle, only insulin is capable of enhancing amphibolite utilization for protein synthesis. PMID- 1910301 TI - Metabolism of ethanol by rat hepatocytes results in generation of a lipid chemotactic factor: studies using a cell-free system and role of oxygen-derived free radicals. AB - We have reported that liver cells metabolizing ethanol release a lipid that has chemotactic activity for human polymorphonuclear leukocytes. The purpose of the present study was to investigate the role of ethanol and of oxygen-derived free radicals in generation of this activity. A cell-free, ethanol-metabolizing system consisting of rat liver cytosol was found to generate a polar lipid which possessed a chemotactic activity identical to the activity from intact cells. The importance of acetaldehyde in this process was established by the findings that (i) an inhibitor of the metabolism of ethanol to acetaldehyde, 4-methylpyrazole, blocked production of the chemotactic lipid; (ii) acetaldehyde could substitute for ethanol; and (iii) cytosol alone incubated with ethanol in the absence of mitochondrial acetaldehyde metabolism generated the activity. Acetaldehyde can serve as a substrate for cytosolic oxidases in reactions that generate radicals (e.g., superoxide anion) which have been shown to attack unsaturated lipids to yield lipid hydroperoxides. When scavengers of oxygen-derived free radicals (superoxide dismutase, catalase, and dimethylsulfoxide) were added to the ethanol metabolizing system they prevented generation of the activity. The data are consistent with a mechanism of chemotactic factor generation by ethanol metabolizing liver cytosol in which acetaldehyde causes formation of oxygen derived free radicals that attack unsaturated cytosolic lipid to generate a polar chemotactic compound. PMID- 1910302 TI - Laser flash photolysis studies of the kinetics of reduction of ferredoxins and ferredoxin-NADP+ reductases from Anabaena PCC 7119 and spinach: electrostatic effects on intracomplex electron transfer. AB - The influence of electrostatic forces on the formation of, and electron transfer within, transient complexes between redox proteins was examined by comparing ionic strength effects on the kinetics of the electron transfer reaction between reduced ferredoxins (Fd) and oxidized ferredoxin-NADP+ reductases (FNR) from Anabaena and from spinach, using laser flash photolysis techniques. With the Anabaena proteins, direct reduction by laser-generated flavin semiquinone of the FNR component was inhibited by complex formation at low ionic strength, whereas Fd reduction was not. The opposite results were obtained with the spinach system. These observations clearly indicate structural differences between the cyanobacterial and higher plant complexes. For the complex formed by the Anabaena proteins, the results indicate that electrostatic forces are not a major contributor to complex stability. However, the rate constant for intracomplex electron transfer had a biphasic dependence on ionic strength, suggesting that structural rearrangements within the transient complex facilitate electron transfer. In contrast to the Anabaena complex, electrostatic forces are important for the stabilization of the spinach Fd:FNR complex, and changes in ionic strength had little effect on the limiting rate constant for intracomplex electron transfer. This suggests that in this case the geometry of the initial collisional complex is optimal for reaction. These results provide a clear illustration of the differing roles that electrostatic interactions may play in controlling electron transfer between two redox proteins. PMID- 1910303 TI - Regulation of CO2 assimilation in oxygenic photosynthesis: the ferredoxin/thioredoxin system. Perspective on its discovery, present status, and future development. PMID- 1910304 TI - Long-term effects of insulin on the enzyme activity and messenger RNA of glycogen synthase in rat hepatoma H4 cells: an effect of insulin on glycogen synthase mRNA stability. AB - Insulin induced glycogen synthase activity and decreased glycogen synthase mRNA concentrations in rat hepatoma H4 cells. Total enzyme activity measured with glucose 6-phosphate gradually increased during a 24-h insulin incubation. The time course of glycogen synthase activation measured by the activity ratio (low G 6-P/high G-6-P) in response to insulin was biphasic with the first peak at 15 min and the second peak at 4 to 6 h. When cells were incubated with insulin and cycloheximide, the first peak persisted while the second peak was abolished. These data suggest that the first activation peak derives from the classic effect of insulin via dephosphorylation and the second peak from an insulin-induced protein synthesis of a glycogen synthase activator. Ribonuclease protection assays with a cloned rat liver glycogen synthase cDNA were used to quantitate glycogen synthase mRNA. Insulin unexpectedly decreased glycogen synthase mRNA in a time- and a dose-dependent manner. After incubation with the RNA synthesis inhibitor, 5, 6-dichloro-1-beta-D-ribofuranosyl benzimidazole (DRB) without and with insulin, the half time of glycogen synthase mRNA decreased from 6.0 +/- 0.80 to 3.9 +/- 0.75 h, respectively. Nuclear run-off experiments with isolated nuclei showed no change of transcription of glycogen synthase mRNA. These data suggest that insulin in this system affects glycogen synthase mRNA stability rather than transcription. PMID- 1910305 TI - Cellular mechanism of synergistic stimulation of PGE2 production by phorbol diester and Ca2+ ionophore A23187 in cultured Madin-Darby canine kidney cells. AB - The synergistic stimulation of arachidonic acid release and prostaglandin (PG) E2 production was observed when quiescent Madin-Darby canine kidney (MDCK) cells were exposed to phorbol 12-myristate 13-acetate (PMA) and Ca2+ ionophore, A23187. Addition of PMA or A23187 by itself was not effective. When cells were treated with 50 nM PMA and 0.1 microM A23187 at a suboptimal concentration, there was a marked increase in the production of PGE2. In the presence of higher concentrations of A23187 (5-10 microM), 50 nM PMA was only synergistic in potentiating the liberation of free arachidonic acid, but failed to stimulate the PGE2 production. The amount of free arachidonic acid liberated by 50 nM PMA and 10 microM A23187 reached a maximum level within several hours, whereas PGE2 synthesis induced by 50 nM PMA and 0.1 microM A23187 proceeded with a slower process requiring more than 24 h to reach a maximum. The stimulated PGE2 synthesis was blocked by transcription and translation inhibitors. The addition of 50 nM PMA alone or the mixture of 50 nM PMA and 0.1 microM A23187 was found similarly to increase the cellular PG endoperoxide synthase activity, suggesting that PMA was responsible for the increased enzyme activity. However, these agents failed to enhance the activities of phospholipases and PGE2 synthase from PGH2. Northern blot analysis confirmed the increased level of PG endoperoxide synthase mRNA in the cells treated with PMA. The effect of PMA was mimicked by other protein kinase C activators. The pretreatment with PMA caused a down-regulation in the PGE2 production. The stimulated PGE2 production was abolished in the presence of selective protein kinase C inhibitors such as staurosporine and H-7. In addition, sphingosine, dihyrosphingosine, and psychosine, recently found to be protein kinase C inhibitors, blocked the effect of PMA in intact MDCK cells. Thus, the results indicate that the synergistically stimulated PGE2 production with phorbol diesters and 0.1 microM A23187 occurred principally through the de novo synthesis of PG endoperoxide synthase, also implying a role for protein kinase C. PMID- 1910307 TI - Interaction of ferredoxin-NADP+ reductase from Anabaena with its substrates. AB - The interaction of ferredoxin-NADP+ reductase from the cyanobacterium Anabaena variabilis with its substrates, NADP+ and ferredoxin, has been studied by difference absorption spectroscopy. Several structural analogs of NADP+ have been shown to form complexes the stabilities of which are strongly dependent on the ionic strength of the medium. In most cases the binding energy of these complexes and their difference absorption spectra are similar to those reported for the spinach enzyme. However, NADP+ perturbs the absorption spectra of the Anabaena and spinach enzymes in a different way. This difference has been shown to be related to the binding of the nicotinamide ring of NADP+ to the enzymes. These results are interpreted as being due to a different nicotinamide binding site in the two reductases. The enthalpic and entropic components of the Gibbs energy of formation of the NADP+ complex have been estimated. An increase in entropy on NADP+ binding seems to be the main source of stability for the complex. A shift of approximately 40 mV in the redox potential of the couple NADP+/NADPH has been observed to occur upon binding of NADP+ to the oxidized enzyme. This allows us to calculate the binding energy between the reductase and NADPH. The ability of the reductase, ferredoxin, and NADP+ to form a ternary complex indicates that the protein carrier binds to the reductase through a different site than that of the pyridine nucleotide. PMID- 1910306 TI - Characterization and molecular properties of 2-oxoglutarate decarboxylase from Euglena gracilis. AB - 2-Oxoglutarate decarboxylase was purified to homogeneity, as judged by polyacrylamide gel electrophoresis. It had a molecular weight of 250,000 and consisted of four identical subunits of molecular weight 62,000. The enzyme was specific for 2-oxoglutarate, but not for other 2-oxo acids such as pyruvate and oxalacetate. Thiamin pyrophosphate and MgCl2 were required for maximum activity. The Km values of the enzyme for 2-oxoglutarate, thiamin pyrophosphate, and MgCl2 were 330, 56, and 93 microM, respectively. 2-Mercaptoethanol and NADP+ augmented significantly the enzyme activity. The amino acid composition and amino acid sequence of the amino-terminal region of 2-oxoglutarate decarboxylase were determined. On ouchterlony double-immunodiffusion gels, the anti-2-oxoglutarate decarboxylase antibody gave sharp precipitin lines against the mitochondrial fraction of E. gracilis and the purified 2-oxoglutarate decarboxylase, but not against pyruvate decarboxylase from Saccharomyces cerevisiae. On Immunoblots of the crude extract of Euglena, the antibody recognized two polypeptides whose molecular weights were 62,000 and 65,000, respectively. The polypeptide with the molecular weight of 62,000 was found only in mitochondrial fractions. In vitro translation of Euglena polyadenylated RNA in a cell-free rabbit reticulocyte lysate system explained the formation of a single polypeptide with a molecular weight of 65,000, suggesting that a putative precursor of 2-oxoglutarate decarboxylase which is about 3000 larger than the subunit of the mature enzyme is synthesized in Euglena cells. PMID- 1910308 TI - Irreversible inhibition of soybean lipoxygenase-1 by hydroperoxy acids as substrates. AB - Soybean lipoxygenase-1 was irreversibly inactivated by various peroxy acids containing a cis,cis-1,4-pentadiene group. Among these compounds, 15(S) hydroperoxyeicosatetraenoic acid (15(S)-HPETE)2 was found to be the most effective in the inactivation of lipoxygenase. Although the prior exposure of 15(S)-HPETE to hemoglobin abolished the inhibitory effect of 15(S)-HPETE, the simultaneous inclusion of hemoglobin potentiated the inactivation of lipoxygenase by 15(S)-HPETE alone. Interestingly, the potentiating effect of hemoglobin was observed only in the incubations with peroxy acids possessing the cis,cis-1,4 pentadiene. In either the presence or the absence of hemoglobin, it was commonly observed that the enzyme inactivation, which was maximal at pH 10, was significantly protected by tocopherol, but neither by mannitol nor ethanol, and that the inclusion of arachidonic acid or linoleic acid prevented the enzyme inactivation. Based on these results, it is suggested that the selective inactivation of lipoxygenase by these peroxy acids may be due to unstable intermediates produced from hydroperoxy acids bound to the active site of lipoxygenase. PMID- 1910309 TI - Effect of pH on the oxidation pathway of dopamine catalyzed by tyrosinase. AB - The oxidation of 3,4-dihydroxyphenylethylamine (dopamine) by O2 catalyzed by tyrosinase yields 4-(2-aminoethyl)-1, 2-benzoquinone (o-dopaminequinone), which evolves nonenzymatically through two branches or sequences of reactions, whose respective operations are determined by the pH of the medium. The cyclization branch of o-dopaminequinone takes place in the entire range of pH and is the only significant branch at pH greater than or equal to 6. The hydroxylation branch of o-dopaminequinone only operates significantly at pH less than 6, and involves the accumulation of 2,4,5-trihydroxyphenylethylamine (6-hydroxydopamine) and 5-(2 aminoethyl)-2-hydroxy-1,4-benzoquinone (p-topaminequinone), identified from cyclic voltammetry assays. The kinetic characterization of the hydroxylation branch of o-dopaminequinone has been carried out by spectrophotometric and oxymetric assays. The successful fitting of data to the kinetic behavior predicted by the kinetic analysis at both pH greater than or equal to 6 and pH less than 6 confirms the overall oxidation pathway proposed for the dopamine oxidation catalyzed by tyrosinase. The antitumoral power of dopamine is possibly enhanced by the high cytotoxicity of 6-hydroxydopamine and p-topaminequinone, accumulated at the acidic pH characteristic of melanosomes and melanome cells. PMID- 1910310 TI - Spheroplast-derived membrane vesicles from Rhodobacter capsulatus cells catalyzing nucleotide transport. AB - Rodobacter capsulatus cells, which were cultured anaerobically in high light intensity, had fewer foldings in the cytoplasmic membrane than those which were grown in lower light intensities. Spheroplast-derived membrane fractions obtained from cells cultured under high light intensity contained a high yield of large right-side-out membrane vesicles. The right-side-out vesicles catalyzed reversible light-induced proton efflux as did intact cells. Nucleotide transport activity was also catalyzed by these membrane vesicles. This activity was indirectly monitored by measurement of photophosphorylation or hydrolysis of externally added diphospho- and triphosphonucleosides. These enzymatic activities occur inside the cytoplasmic membrane of spheroplasts and membrane vesicles and therefore require the transport of the externally added reagents. The indirect measurements of transport were complemented by the demonstration of direct uptake of radiolabeled nucleotides into the membrane vesicles. These data support the suggestion that a nucleotide transporter located in the cytoplasmic membrane of R. capsulatus bacteria mediates these activities. PMID- 1910311 TI - Preparation and characterization of monoclonal antibodies against soybean seed lipoxygenase isoenzymes. AB - Sets of monoclonal antibodies have been prepared using two soybean seed lipoxygenase isoenzymes as the antigens. The antibodies were characterized by ELISA, Western blot analysis, immunoprecipitation, and in kinetic assays. Several antibodies displaying selectivity for the two closely related polypeptides were obtained, while the majority of the antibodies generated were crossreactive. Antibodies specific to the native and denatured forms of the two proteins were also obtained. Two of the monospecific antibodies were shown to immunoprecipitate the appropriate isoenzyme selectively from a mixture. When these antibodies were immobilized on agarose, they were successful in the immunoaffinity purification of the individual isoenzymes. In kinetic experiments certain antibodies were found to influence catalysis upon incubation with lipoxygenase. Antibodies which both inhibited and stimulated catalysis were identified. PMID- 1910312 TI - Free radical-induced alterations of myocardial membrane proteins. AB - Rat myocardial membranes exposed to the free radical-generating systems, Fe2+/ascorbate, Cu2+/t-butylhydro-peroxide, linoleic acid hydroperoxide, and soybean lipoxygenase (Type I) undergo lipid peroxidation. This is evidenced by the accumulation of thiobarbituric acid-reactive substances and the loss of both extractable phospholipids and their polyunsaturated acyl groups. Lipid peroxidation is accompanied by alterations of membrane proteins including the general loss of polypeptides and accumulation of high-molecular weight material. The most sensitive protein is a polypeptide with a molecular weight of 28 kDa. At low levels of oxidation, this protein moves incrementally to slightly higher apparent molecular weight. At higher oxidant levels or longer periods of oxidation, the protein disappears completely from the SDS-PAGE gel. The "28K reaction" occurs prior to the massive, oxidant-induced lipid alterations and may thus indicate specific adduct formation between this protein and certain peroxidized membrane phospholipids. PMID- 1910314 TI - Superoxide dismutase triggers activation of "primed" platelets. AB - Superoxide dismutase (SOD) triggers activation of human platelets exposed to subthreshold concentrations of arachidonic acid and collagen. The subthreshold concentrations used are not able to activate platelets but "prime" platelets to be activated by SOD. The addition of SOD to arachidonic acid-or collagen-primed platelets induced aggregation, thromboxane A2 production, and release of [3H]serotonin. Superoxide dismutase does not have any effect on resting platelets and ADP-, thrombin-, calcium ionophore A23187-, PAF-, or U46619-stimulated platelets. Furthermore, superoxide dismutase-dependent platelet activation is fully prevented by catalase and/or aspirin, suggesting a role for H2O2 and the involvement of the cyclooxygenase pathway of arachidonic acid in such activation. PMID- 1910313 TI - Inhibition of rat brain prostaglandin D synthase by inorganic selenocompounds. AB - Various inorganic selenocompounds dose-dependently inhibited the rat brain prostaglandin (PG) D synthase, both in the purified enzyme preparation and in the crude brain supernatant. All of the quadrivalent selenium compounds tested had a very limited range of IC50 values in the purified enzyme (11-12 microM) and in the brain supernatant (9-15 microM). A divalent selenium compound was also inhibitory, but a hexavalent selenium compound was ineffective. In contrast, organic selenocompounds such as selenomethionine and selenourea had no effect on the PGD synthase activity. Furthermore, sodium sulfate and sodium sulfite up to 10 mM did not inhibit the activity. The inhibition by selenium required the preincubation of the metal with sulfhydryl compounds such as dithiothreitol (DTT), indicating that the formation of selenotrisulfide or some other adduct(s) is essential for the inhibition. Furthermore, the inhibition was reversed by an excess amount of dithiothreitol, suggesting that the selenotrisulfide derivative of DTT binds to the SH group of the PGD synthase. The kinetic analysis revealed the inhibition by selenite to be noncompetitive with a Ki value of 10.1 microM. On the other hand, glutathione-dependent PGD synthase from rat spleen was much less inhibited, and PGF synthase and PGD2 11-ketoreductase activities were not inhibited by the selenium compound. PMID- 1910315 TI - Mechanism of cobalt (II) ion inhibition of iron-supported phospholipid peroxidation. AB - Co2+ inhibited nonenzymatic iron chelate-dependent lipid peroxidation in dispersed lipids, such as ascorbate-supported lipid peroxidation, but not iron independent lipid peroxidation. Histidine partially abolished the Co2+ inhibition of the iron-dependent lipid peroxidation. The affinity of iron for phosphatidylcholine liposomes in Fe(2+)-PPi-supported systems was enhanced by the addition of an anionic lipid, phosphatidylserine, and Co2+ competitively inhibited the peroxidation, while the inhibiting ability of Co2+ as well as the peroxidizing ability of Fe(2+)-PPi on liposomes to which other phospholipids, phosphatidylethanolamine, or phosphatidylinositol had been added was reduced. Co2+ inhibited microsomal NADPH-supported lipid peroxidation monitored in terms of malondialdehyde production and the peroxidation monitored in terms of oxygen consumption. The inhibitory action of Co2+ was not associated with iron reduction or NADPH oxidation in microsomes, suggesting that Co2+ does not affect the microsomal electron transport system responsible for lipid peroxidation. Fe(2+) PPi-supported peroxidation of microsomal lipid liposomes was markedly inhibited by Co2+. PMID- 1910316 TI - Lipid peroxide makes rabbit platelet hyperaggregable to agonists through phospholipase A2 activation. AB - Treatment of rabbit platelets with tert-butyl hydroperoxide and Fe2+ caused increasing arachidonic acid release, lysophosphatidylcholine formation, and aggregation with increasing concentrations of Fe2+. A combination of tert-butyl hydroperoxide and a low concentration of Fe2+, which by itself causes slight or no such activation, elicited synergistic release of arachidonic acid and aggregation under stimulation with a suboptimal concentration of collagen or arachidonic acid as an agonist. These responses were inhibited by pretreatment of the platelets with vitamin E or mepacrine in a concentration-dependent manner, but not by uric acid. The arachidonic acid release was dependent on the presence of Ca2+ in the medium. Synergistic formation of lysophosphatidylcholine, but not diacylglycerol, was also observed under this condition. The aggregation was also inhibited by indomethacin, a cyclooxygenase inhibitor. Cyclooxygenase activity was not affected by the oxidative treatment. These results suggest that lipid peroxide formed in membranes causes phospholipase A2 to become hypersusceptible to the agonist used, making the platelets hyperaggregable. PMID- 1910317 TI - Calcium-dependent autophosphorylation of the glucose-regulated protein, Grp78. AB - The characteristics of phosphorylation of the 78-kDa glucose-regulated protein (Grp78), also known as the immunoglobulin heavy chain binding protein, were studied in vitro and in vivo. The purified protein from either calf liver or bovine kidney cells (MDBK) could be phosphorylated in vitro with [gamma-32P]ATP, in a reaction that is stimulated by Ca2+ and inhibited by the Ca(2+)-chelator ethylene glycol bis(beta-aminoethyl ether)N,N'-tetraacetic acid (EGTA). In the presence of EGTA, excess Ca2+ increased the rate of phosphorylation about 18 fold. Based on EGTA/Ca2+ titrations, the optimal Ca2+ concentration for phosphorylation was estimated to be 10-50 microM. Other divalent cations such as Mg2+, Mn2+, and Zn2+ were found to be inhibitory as was the Ca2+ antagonist lanthanum (La3+). The in vivo phosphorylation of Grp78 was studied in MDBK cells labeled with 32Pi. In the presence of inducers of Grp78 synthesis, such as ionomycin, tunicamycin, or 2-deoxyglucose, there was a large increase in the level of Grp78 in the cells but a decrease in the amount of phosphorylated protein. Two-dimensional gel analysis of Grp78 purified from bovine liver and MDBK cells identified at least four isoforms. After in vivo and in vitro phosphorylation of Grp78 all the acidic isoforms contained radioactivity but not the most basic isoform. Phosphoamino acid analysis of Grp78 showed that serine and threonine were phosphorylated in vivo and only threonine was phosphorylated in vitro. PMID- 1910318 TI - Separation and partial characterization of enzymes catalyzing delta aminolevulinic acid formation in Synechocystis sp. PCC 6803. AB - Formation of the universal tetrapyrrole precursor, delta-aminolevulinic acid (ALA), from glutamate via the five-carbon pathway requires three enzymes: glutamyl-tRNA synthetase, glutamyl-tRNA reductase, and glutamate-1-semialdehyde (GSA) aminotransferase. All three enzymes were separated from extracts of the unicellular cyanobacterium Synechocystis sp. PCC 6803, and two of them, glutamyl tRNA synthetase and GSA aminotransferase, were partially characterized. After an initial high speed centrifugation and differentiatial ammonium sulfate fractionation of cell extract, the enzymes were separated by successive affinity chromatography on Reactive Blue 2-Sepharose and 2',5'-ADP-agarose. All three enzyme fractions were required to reconstitute ALA formation from glutamate. The apparent native molecular masses of glutamyl-tRNA synthetase and GSA aminotransferase were determined by gel filtration chromatography to be 63 and 98 kDa, respectively. Neither glutamyl-tRNA synthetase nor GSA aminotransferase activity was affected by hemin concentrations up to 10 and 30 microM, respectively, and neither activity was affected by protochlorophyllide concentrations up to 2 microM. GSA aminotransferase was inhibited 50% by 0.5 microM gabaculine. The gabaculine inhibition was reversible for up to 1 h after its addition, if the gabaculine was removed by gel filtration before the enzyme was incubated with substrate. However, irreversible inactivation was obtained by preincubating the enzyme at 30 degrees C either for several hours with gabaculine alone or for a few minutes with both gabaculine and GSA. Neither pyridoxal phosphate nor pyridoxamine phosphate significantly affected the activity of GSA aminotransferase at physiologically relevant concentrations, and neither of these compounds reactivated the gabaculine-inactivated enzyme. It was noted that the presence of pyridoxamine phosphate in the ALA assay mixture produced a false positive color reaction even in the absence of enzyme. PMID- 1910319 TI - Affinity labeling of a subsite of Taka-amylase A by the fluorescent reagent o phthalaldehyde. AB - A cross-linked modification of Lys residue located at the subsite of the enzyme active site of Taka-amylase A was attained by the use of the fluorescent reagent of o-phthalaldehyde (OPA). The fluorescence and uv absorption at 337 nm derived from the isoindole ring, which was produced by cross-linking through the epsilon amino group of Lys and the thiol group of the Cys residue, provided the evidence for the OPA-mediated inactivation of Taka-amylase A. Kinetic analysis showed that 1 mol of OPA per mole of enzyme was incorporated, which corresponded closely with the value obtained by the uv absorption. Because the OPA inactivation was retarded by the substrate analog of alpha-cyclodextrin, OPA modification was classified as a type of affinity labeling reaction. A remarkable increase in the pI value from 4.0 to 5.6 upon the modification led to clear separation of the modified enzyme from the native Taka-amylase A by a DEAE-Sephacel column and led to the charge isomer pattern on gel electrophoresis performed according to the method of Hedrick and Smith. Moreover, the affinity gel electrophoresis showed that the modified enzyme completely lost the affinity for the substrate soluble starch, which indicated that the subsite modification occurred. PMID- 1910320 TI - Metabolism of cyanide by Phanerochaete chrysosporium. AB - The oxidation of veratryl alcohol (3,4-dimethoxybenzyl alcohol) by lignin peroxidase H2 (LiP H2) from the white rot fungus Phanerochaete chrysosporium was strongly inhibited by sodium cyanide. The I50 was estimated to be about 2-3 microM. In contrast, sodium cyanide binds to the native enzyme with an apparent sodium cyanide dissociation constant Kd of about 10 microM. Inhibition of the veratryl alcohol oxidase activity of LiP H2 by cyanide was reversible. Ligninolytic cultures of P. chrysosporium mineralized cyanide at a rate that was proportional to the concentration of cyanide to 2 mM. The N-tert-butyl-alpha phenylnitrone-cyanyl radical adduct was observed by ESR spin trapping upon incubation of LiP H2 with H2O2 and sodium cyanide. The identity of the spin adduct was confirmed using 13C-labeled cyanide. Six-day-old cultures of the fungus were more tolerant to sodium cyanide toxicity than spores. Toxicity measurements were based on the effect of sodium cyanide on respiration of the fungus as determined by the metabolism of [14C]glucose to [14C]CO2. We propose that this tolerance of the mature fungus was due to its ability to mineralize cyanide and that this fungus might be effective in treating environmental pollution sites contaminated with cyanide. PMID- 1910321 TI - Haemolytic disease of the newborn infant. Long term efficiency of the screening and the prevention of alloimmunization in the mother: thirty years of experience. AB - During the last thirty years, the diagnosis, management and prevention of haemolytic disease of the newborn infant (HDN) have improved. From 1959 to 1988, 3004 HDN (ABO excluded) have been collected. The percentage of HDN with anti-D alloimmunization decreased significantly (98.4% from 1959 to 1968, 93.5% from 1969 to 1978 and 68.1% from 1979 to 1988). The anti-D HDN with exchange transfusion (ET) fell significantly between the first and second periods (577 versus 970; chi 2 = 19.92; P less than 0.001). On the other hand, the number of HDN other than anti-D increased during these three periods, but the percentage of these HDN which needed ET decreased. Our study shows the long term efficiency of the prevention of anti-D alloimmunization (since 1970) and of the irregular antibodies screening among all pregnant women (since 1979). PMID- 1910322 TI - Isolation and characterization of membrane-associated placental proteins. AB - Membrane-associated proteins (MPs) of the human term placenta (afterbirth) were obtained by extracting the insoluble part of the tissue with solubilizing agents, after the soluble material had been removed by washing with saline. The insoluble residue was subsequently exhaustively extracted first with the nonionic detergent Triton X-100 and then with 6 M urea. In the Triton extract eleven new different membrane-associated antigens could be detected by immunochemical methods; they were designated as MP2A to MP2L. One of these proteins (MP2C) was found to be immunochemically identical with the already described soluble placental protein PP21 [3]. MP1 another antigen detected in the Triton extract later was identified as heart stable alkaline phosphatase. In the urea extract eight different membrane-associated antigens could be identified by immunochemical methods; they were designated as MP3 to MP10. MP3 later was found to be immunochemically identical with laminin. All these membrane-associated proteins have now been isolated to purity and characterized by their physico-chemical properties. Specific antisera to the new proteins were obtained by immunizing animals with the corresponding purified proteins. They were used to detect and quantitate the new proteins in extracts of placentas and other human tissues by immunochemical methods such as gel diffusion tests. The immunocytochemical localization of the new proteins as well as measurement of their concentrations in body fluids by sensitive radioimmunoassays or enzyme immunoassays are presently under investigation. PMID- 1910323 TI - Cerebral perfusion during canine hypothermic cardiopulmonary bypass: effect of arterial carbon dioxide tension. AB - Cerebral blood flow (radioactive microspheres), intracranial pressure (subdural bolt), and retinal histopathology were examined in 20 dogs undergoing 150 minutes of hypothermic (28 degrees C) cardiopulmonary bypass to compare alpha-stat (arterial carbon dioxide tension, 40 +/- 1 mm Hg; n = 10) and pH-stat (arterial carbon dioxide tension, 61 +/- 1 mm Hg; n = 10) techniques of arterial carbon dioxide tension management. Pump flow (80 mL.kg-1.min-1), mean aortic pressure (78 +/- 2 mm Hg), and hemoglobin level (87 +/- 3 g/L [8.7 +/- 0.3 g/dL]) were maintained constant. During bypass, intracranial pressure progressively increased in the alpha-stat group from 6.0 +/- 1.0 to 13.9 +/- 1.8 mm Hg (p less than 0.05) and in the pH-stat group from 7.7 +/- 1.1 to 14.7 +/- 1.4 mm Hg (p less than 0.05), although there was no evidence of loss of intracranial compliance or intracranial edema formation as assessed by brain water content. With cooling, cerebral blood flow decreased by 56% to 62% in the alpha-stat group (p less than 0.05) and by 48% to 56% in the pH-stat group (p less than 0.05). However, 30 minutes after rewarming to 37 degrees C, cerebral blood flow in both groups failed to increase and remained significantly depressed compared with baseline values. Both groups showed similar amounts of ischemic retinal damage, with degeneration of bipolar cells found in the inner nuclear layer in 67% of animals. We conclude that, independent of the arterial carbon dioxide tension management technique, (1) cerebral perfusion decreased comparably during prolonged hypothermic bypass, (2) intracranial pressure increases progressively, (3) ischemic damage to retinal cells occurs despite maintenance of aortic pressure and flow, and (4) a significant reduction in cerebral perfusion persists after rewarming. PMID- 1910324 TI - [The structure and antimicrobial activity of the partial degradation products of the antibiotic eremomycin]. AB - Antimicrobial activity of partial degradation products of eremomycin, a new glycopeptide antibiotic, was studied. The products formed by eremomycin deglycosylation (deseremosaminyl eremomycin, eremosaminyl aglycone and aglycone) and elimination of the chlorine atom from the molecule aglycone moiety (dechloroeremomycin). The spectral data in favour of the compounds structure are presented. It was found that partial degradation led to a decrease in the antimicrobial activity of the antibiotic. Dechloreremomycin had the highest activity among the products. Its MIC for the methicillin-resistant strains of Staphylococcus aureus was only twice as low as that of the initial antibiotic. PMID- 1910325 TI - [Modern biological methods for evaluating antibiotic activity]. PMID- 1910326 TI - [Our experience with flecainide acetate in resistant arrhythmias in children. Apropos of 35 cases]. AB - Thirty-five patients aged 6 days to 18 years (average 7.5 +/- 5.2 years) were treated for an average period of 16 months (range 8 days to 50 months) with flecainide acetate at an average dose of 4.8 +/- 1.4 mg/kg (2.9 to 10 mg/kg) or 130 +/- 30.5 mg/m2 administered twice daily. The cardiac arrhythmia was a resistant paroxysmal junctional tachycardia due to a Wolff-Parkinson-White syndrome in 27 cases, intranodal reentry in 6 cases and a chronic reciprocating rhythm in 2 cases. Treatment was successful with complete suppression of the tachycardia in 24 cases. Partial success with a good clinical result was obtained in 4 cases and there were 7 failures, 6 due to inefficacy of the drug, and 1 because of an extracardiac secondary effect. One case of incessant junctional tachycardia was observed in a 9 month old child in whom the preexcitation disappeared. Atrioventricular preexcitation persisted in 20 out of 24 cases. The duration of the non-preexcited QRS complexes increased significantly from 73.6 +/ 13.8 to 82.2 +/- 15.2 ms; n = 14, p less than 0.01. The minimal effective plasma concentration was 347 +/- 147 ng/ml. The plasma concentration/dose ratio of children over 4 years of age was the same as in adults. It was significantly higher in babies and infants suggesting a progressive acquisition of the capacity to metabolise flecainide during the first year of life. In conclusion, flecainide acetate was easy to use with respect to administration and follow-up, and seems to be a drug of choice for the treatment of junctional tachycardia in children. PMID- 1910327 TI - [Ventricular "remodeling" after myocardial infarction]. AB - Cardiac failure is the principal medium-term complication of myocardial infarction. Changes in left ventricular geometry are observed after infarction, called ventricular remodeling, which, though compensatory initially, cause ventricular failure in the long-term. Experimental and clinical studies suggest that early treatment by coronary recanalisation, trinitrin and angiotensin converting enzyme inhibitors may prevent or limit the expansion and left ventricular dilatation after infarction, so improving ventricular function, and, at least in the animal, reduce mortality. Large scale trials with converting enzyme inhibitors are currently under way to determine the effects of this new therapeutic option. It would seem possible at present, independently of any reduction in the size of the infarction, to reduce or delay left ventricular dysfunction by interfering with the natural process of dilatation and ventricular modeling after infarction. PMID- 1910328 TI - Comparative biochemistry of mouse and chick secondary-palate development in vivo and in vitro with particular emphasis on extracellular matrix molecules and the effects of growth factors on their synthesis. AB - A biochemical study analysing the wet weight, dry weight, water, protein and DNA content, collagen and GAG composition of all stages of the developing secondary palate in vivo and in vitro was undertaken to investigate differences between a species in which the palatal shelves elevate (mouse) and one in which they do not (chick). The effects of EGF, bFGF, PDGF and TFG-beta 1 on collagen and GAG synthesis by cultured mouse and chick palatal shelves of different embryonic stages were also studied. The total GAG content of developing mouse palatal shelves decreased with developmental time; heparan sulphate proteoglycan formed the major species in early palates but hyaluronan was the major species in mid late palates. There was a peak of hyaluronan synthesis in embryonic palatal shelves in vitro at day 13 (T.21), i.e. immediately before shelf elevation. By contrast the total GAG content of chick palates increased with development; chondroitin-6-sulphate formed the major GAG species and there was no peak in hyaluronan synthesis. The water content of developing murine palates rose rapidly at day 14 (T.22), i.e. the time of shelf elevation. No such peak was seen in the chick, where the water content rose exponentially with developmental time. Mouse palates synthesized chondroitin-4-sulphate and novel proteins around the time of shelf elevation; chick palates synthesized chondroitin-6-sulphate and no novel proteins at any developmental stage. Collagen synthesis also peaked in vitro in T.21 murine palates. EGF markedly stimulated murine palatal collagens and GAG synthesis between stages T.20-T.22, but had no effect thereafter. Basic FGF had similar but smaller stage-related effects. PDGF had no effect on mouse palatal collagen and GAG synthesis whilst TGF-beta 1 inhibited GAG synthesis at T.21. The ratios of collagens I, III and V produced by mouse palates were unaltered by the growth factors. All the growth factors had no effect on chick palatal collagen synthesis at any stage and minimal effect on GAG synthesis; TGF-beta 1 stimulated it in early but inhibited it in mid- to late-stage chick palates. These data indicate that extracellular matrix molecule metabolism within the palate is markedly different in the two species studied and suggest that the differing profiles of such molecules may be regulated at certain developmental stages by specific growth factors. PMID- 1910330 TI - Purification and characterization of an endoxylanase from Trichoderma koningii G 39. AB - Trichoderma koningii G-39 produced xylanases in submerged culture using oat spelt xylan or crystalline cellulose, Avicel, as the sole carbon source. A low-Mr xylanase was purified from the culture filtrate by ion-exchange chromatography on SP-Trisacryl-M and gel filtration on Fractogel TSK HW-50F. It was homogeneous on SDS/PAGE and isoelectric focusing. A typical procedure provided about 11-fold purification with 4.5% protein yield and 50% activity recovery. The purified enzyme has an Mr value of about 21,500 and a pI of 8.9. Its specific activity was 6100 units/mg of protein, with optimal activity towards 0.5% xylan at about pH 5.5 and 60 degrees C. The purified enzyme had no activity against CM-cellulose with a degree of substitution of 0.63. It also showed no beta-xylosidase activity. The Km and Vmax. values, as determined with the soluble fraction of oat spelt xylan as substrate, were 0.70 mg/ml and 1.85 x 10(6) mumol/min per mg of enzyme respectively. Hg2+ (1 mM) and SDS (10 mM) completely inhibited xylanase activity, whereas Ca2+ showed no significant effect on the enzyme activity at 1 mM, but gave 80% inhibition at 10 mM. The enzyme contained about 4.4% carbohydrate and showed an immunological relationship to a cellobiohydrolase from the same fungal strain. PMID- 1910331 TI - Cloning and stable expression of a new member of the human liver phenol/bilirubin: UDP-glucuronosyltransferase cDNA family. AB - A new human liver UDP-glucuronosyltransferase (HlugP4) has been cloned and expressed in cell culture. The expressed enzyme has a molecular mass of 56 kDa and preferentially catalysed the glucuronidation of halogenated and bulky alkyl phenols. The C-terminal half of the sequence (246 amino acids) is 96% identical with the same portion of HlugP1, whereas the N-terminal half of the deduced protein sequences are only 38% identical. These results suggest that the two isoenzymes may be derived from the same gene by differential splicing of the gene product. PMID- 1910332 TI - beta-deuterium kinetic isotope effects in the purine nucleoside phosphorylase reaction. AB - 1. [2'-2H]Inosine was made from inosine by tetraisopropyldisiloxanyl protection of the 3'- and 5'-positions, oxidation with dimethyl sulphoxide and acetic anhydride, immediate NaB2H4 reduction of the oxo sugar product and inversion at C 2' of the resultant protected [2'-2H]arabino-inosine by trifluoromethanesulphonylation and reaction with caesium propionate, followed by deprotection. 2. The equilibrium-perturbation technique was used to measure beta 2H(V/K) for phosphorolysis of this compound by the purine nucleoside phosphorylase of Escherichia coli as a function of pH. 3. The pH variation indicates an intrinsic effect of 1.068 masked by isotopically silent steps near the pH optimum. 4. The similar pH variation of these beta-deuterium effects and the alpha-deuterium effects measured previously [Stein & Cordes (1981) J. Biol. Chem. 256, 767-772; Lehikoinen, Sinnott & Krenitsky (1989) Biochem. J. 257, 355 359] for this reaction provides the first experimental reassurance for the common assumption that pH changes merely mask and unmask the chemical steps in an enzyme catalysed reaction, and do not detectably alter transition-state structure. 5. The dihedral angle between the C-H-2' bond and the electron-deficient p-orbital at the transition state is in the range 32-48 degrees, in accord with an essentially planar furanose ring. PMID- 1910329 TI - Xenopus transcription factors: key molecules in the developmental regulation of differential gene expression. PMID- 1910333 TI - Asymmetrical distribution of G-proteins among the apical and basolateral membranes of rat enterocytes. AB - The distribution of the alpha and beta subunits of guanosine-nucleotide-binding proteins (G-proteins) among the apical and basolateral membranes of polarized rat enterocytes was investigated by ADP-ribosylation assays in vitro and immunoblotting with G-protein-subunit-specific antisera. The enterocytes were found to express alpha i2, alpha ji3, alpha s and beta subunits, whereas alpha i1 and alpha o subunits could not be detected. The alpha i2 and alpha i3 subunits were located predominantly in the basolateral membrane, in contrast with the alpha s and beta subunits, which were distributed uniformly among both membranes. Furthermore, 39 kDa and 78 kDa proteins, recognized by anti-alpha i1/2 but not anti-alpha i1 or anti-alpha i3 specific antisera, and resistant to ADP ribosylation by pertussis toxin, were localized exclusively at the apical border. These Gi-related proteins might represent novel members of the G-protein family. Activation of apical G-proteins by GTP or its analogues failed to release the alpha s, alpha i and beta subunits or the 39 kDa and 78 kDa alpha i-like proteins from the membrane, suggesting a functional role for these proteins in the apical membrane itself. Our recent finding of a guanosine 5'-[gamma-thio]triphosphate sensitive Cl- conductance in the apical membrane of rat enterocytes suggests that one or more of these G-proteins may act as local regulators of specific apical transport functions. PMID- 1910334 TI - Purification and partial characterization of a novel lectin from elder (Sambucus nigra L.) fruit. AB - A previously unknown haemagglutinin, named Sambucus nigra agglutinin-III (SNA III), has been purified from the fruit of the elder (Sambucus nigra). Whereas elder bark agglutinin I (SNA-I) is highly specific for terminal alpha 2,6-linked sialic acid residues, SNA-III displays a high affinity for oligosaccharides containing exposed N-acetylgalactosamine and galactose residues. Different N terminal sequences and the amino acid composition distinguish the fruit lectin from elder bark agglutinin II (SNA-II), which shows a similar carbohydrate specificity. The 40-fold higher affinity of SNA-III for asialofetuin than for human asialo-alpha 1-acid glycoprotein and human asialotransferrin respectively suggests a preference for O-linked glycans. SNA-III occurs mainly as a monomeric glycoprotein, but tends to form di- and oligo-meric aggregates. This aggregation seems to mediate the multivalent interaction, leading to agglutination. SDS/PAGE revealed two major polypeptides with apparent molecular masses of 32 and 33 kDa respectively. This heterogeneity is probably a result of proteolysis in the C terminal region. Binding to concanavalin A and susceptibility to peptide: N glycosidase F indicated the presence of N-glycosidically linked oligosaccharides. PMID- 1910336 TI - A non-reducing terminal fragment from tracheal cartilage keratan sulphate chains contains alpha (2-3)-linked N-acetylneuraminic acid. AB - Keratan sulphate chains were isolated from bovine tracheal ring cartilage (15-18 month-old animals) after papain digestion of the tissue followed by ethanol fractionation, chondroitinase ABC digestion and alkaline borohydride reduction. The keratan sulphate chains were further purified by anion-exchange chromatography on a Pharmacia Mono-Q column in order to remove any contaminating chondroitin sulphate and O-linked oligosaccharides. The chains were then treated with keratanase and the digest was subjected to alkaline borohydride reduction, producing oligosaccharides with galactitol at their reducing ends. The reduced digest was chromatographed on a Nucleosil 5 SB anion-exchange column and individual oligosaccharides were isolated. One of these, oligosaccharide (I), was shown by 500 MHz 1H-n.m.r. spectroscopy to have the following structure: NeuAc alpha 2-3Gal beta 1-4GlcNAc(6SO4) beta 1-3Gal-ol (I) The structure of this oligosaccharide shows that keratan sulphate chains from bovine tracheal ring cartilage may be terminated with N-acetylneuraminic acid linked alpha (2-3) to an unsulphated galactose. Keratan sulphate chains were also isolated from bovine femoral head cartilage (15-18-month-old animals) using an identical protocol, but with keratanase which was subsequently shown to have sialidase activity. This yielded oligosaccharide (II), the unsialyated version of (I): Gal beta 1 4GlcNAc(6SO4) beta 1-3Gal-ol (II). PMID- 1910335 TI - The mutation Lys234His yields a class A beta-lactamase with a novel pH dependence. AB - The lysine-234 residue is highly conserved in beta-lactamases and in nearly all active-site-serine penicillin-recognizing enzymes. Its replacement by a histidine residue in the Streptomyces albus G class A beta-lactamase yielded an enzyme the pH-dependence of which was characterized by the appearance of a novel pK, which could be attributed to the newly introduced residue. At low pH, the kcat, value for benzylpenicillin was as high as 50% of that of the wild-type enzyme, demonstrating that an efficient active site was maintained. Both kcat. and kcat/Km dramatically decreased above pH 6 but the decrease in kcat./Km could not be attributed to larger Km values. Thus a positive charge on the side chain of residue 234 appears to be more essential for transition-state stabilization than for initial recognition of the substrate ground state. PMID- 1910338 TI - The in vivo disposition of aflatoxin B1 in rat liver. AB - The disposition of a non-toxic i.p. dose of [3H]-aflatoxin B1 (0.70 micrograms/kg) in the blood, plasma, and liver was studied in male Wistar rats. Uptake into the blood, plasma, and liver was biphasic; there was an initial rapid rise (0-2 hr) followed by a second phase (2-12 hr) of a gradual increase. Most of the radioactivity in the blood was bound noncovalently to albumin. Distribution of radioactivity in the subcellular fractions of liver showed that the microsomes exhibited the highest labeling which increased over the time course; labeling of the cytosol reached a maximum at 2 hr then decreased to a new steady state, whereas the mitochondria and nuclei reached a plateau. When the content of aflatoxin B1 in the nuclear subfractions was examined, greater than 92% of the total radioactivity was found in the deoxyribonucleoprotein fraction, and 84% of this was bound noncovalently. These results suggest that aflatoxin B1 is transported from the site of injection through the blood to the liver and its subcellular and subnuclear fractions primarily in a noncovalent form. PMID- 1910337 TI - Inhibition of Ca2+ inflow causes an abrupt cessation of growth-factor-induced repetitive free Ca2+ transients in single NIH-3T3 cells. AB - In single NIH-3T3 fibroblasts loaded with fura-2, bombesin induced one of three patterns of increase in the concentration of intracellular free Ca2+ [( Ca2+]i): a single transient increase, a sustained increase, or repetitive transient increases in [Ca2+]i. Foetal-calf serum and ATP also gave these three patterns of response, although a lower proportion of cells gave repetitive Ca2+ transients in response to ATP. An increase in the concentration of bombesin from 1 to 25 nM increased the proportion of cells which exhibited repetitive Ca2+ transients. At 25 nM-bombesin, the proportion of cells which exhibited repetitive Ca2+ transients increased as the extracellular Ca2+ (Ca2+o) concentration was increased from 1 to 5 mM. Removal of Ca2+o by addition of EGTA, or inhibition of Ca2+ inflow by treatment of cells incubated in the presence of Ca2+o with verapamil or an activator of protein kinase C, abruptly terminated repetitive Ca2+ transients, with only one transient observed after the cessation of Ca2+ inflow. Repetitive Ca2+ transients were not observed in cells incubated in the absence of Ca2+o and in the presence of EGTA. Addition of Ca2+o to cells previously incubated in the presence of EGTA caused a resumption of repetitive Ca2+ transients. Addition of thapsigargin alone induced a large transient increase in [Ca2+]i, whereas much smaller transient increases in [Ca2+]i were induced in about 30% of cells tested by caffeine or carbonyl cyanide m chlorophenylhydrazone (CCCP) plus oligomycin. Thapsigargin or the combination of CCCP plus oligomycin completely inhibited bombesin-induced repetitive Ca2+ transients, whereas caffeine had no effect. It is concluded from the studies of the role of Ca2+o that NIH-3T3 cells differ from other cell types in the anatomical or chemical links between extracellular Ca2+ and the intracellular stores involved in the generation of Ca2+ transients, whereas the results of the experiments with inhibitors indicate that the generation of repetitive Ca2+ transients in NIH-3T3 cells is unlikely to involve Ca(2+)-induced Ca2+ release from caffeine-sensitive stores. PMID- 1910339 TI - Displacement of apolipophorin III from the surface of low density lipophorin by human apolipoprotein A-I. AB - A hybrid low density lipophorin particle (LDLp) was prepared by incubation with human apolipoprotein (apo) A-I in vitro. ApoA-I associated with LDLp in a concentration dependent, saturable manner which was accompanied by dissociation of apolipophorin III (apoLp-III). The apoA-I hybrid LDLp had the same lipid composition, density and morphology as native LDLp indicating that displacement of apoLp-III by apoA-I did not affect its structural properties. The molar ratio of apoLp-I:apoLp-II:apoLp-III was maximally reduced from 1:1:16 to 1:1:2 in native versus hybrid LDLp with the latter particle binding 7 molecules of apoA-I. The inability of apoA-I to displace the remaining 2 apoLp-III supports the concept that these apoLp-III molecules are not equivalent to the other fourteen. Native and hybrid LDLp particles were both metabolized to high density lipophorin in vivo. The displacement reaction represents a novel method for the production of apolipoprotein hybrids of LDLp and the results indicate that apoA-I has an inherently higher affinity for lipid surfaces than apoLp-III. PMID- 1910340 TI - Purification of a protease inhibitor which controls prophenoloxidase activation in hemolymph of Locusta migratoria (insecta). AB - A protein which inhibits the prophenoloxidase----phenoloxidase (EC 1.14.18.1) proteolytic activation in hemocyte extracts of Locusta migratoria was isolated from the plasma of the same insect and partially characterized. It shows a molecular weight of 14,000, an inhibiting activity toward the cascade system in the insect hemocytes, which resulted in a lower production of phenoloxidase, a key enzyme for the defence mechanism in arthropods. To identify the specificity of the Locusta inhibitor and consequently the specificity of its target enzyme, inhibitory tests were performed against a number of known serine-proteases. A strong in vitro inhibiting activity toward chymotrypsin and, to a lesser extent, toward human leukocyte elastase was present, while trypsin, Carlsberg subtilisin, human thrombin and pancreatic elastase failed to react. The lack of trypsin inhibition by the isolated inhibitor suggested that the trypsin-catalysed activation of the system in the hemocyte extract takes place under different controls or at an earlier stage of the cascade. The N-terminal sequence of the inhibitor reveals that this molecule is different from the protease inhibitors isolated from other arthropods. PMID- 1910341 TI - Quantitation of mitochondrial DNA carrying tRNALys mutation in MERRF patients. AB - An A to G transition at nucleotide position 8,344 in tRNALys of mitochondrial DNA has been recently identified as a causative mutation of myoclonus epilepsy associated with ragged-red fibers (MERRF). To investigate if the degree of heteroplasmy of mitochondrial DNA is correlated with the severity of MERRF, we have developed a novel method for quantitation of the mutant mitochondrial DNA by polymerase chain reaction using a mismatched primer. With the method, populations of mutant mtDNAs from 5 cases of MERRF carrying the tRNALys mutation were analyzed. The tight linkage of the severity of symptoms and the degree of heteroplasmies is not necessarily observed for all cases, though there is a tendency that patients with less wild type mtDNAs show severer clinical symptoms and earlier onset. PMID- 1910342 TI - [Evaluation of pharmacodynamic equivalence of glycerol trinitrate-containing sprays for oral administration with or without chlorofluorocarbons ]. AB - Evaluation of Pharmacodynamic Equivalence of Glyceryl Trinitrate Sprays for Oral Application with or without Fluorochlorohydrocarbons. The pharmacodynamic equivalence of a fluorochlorohydrocarbons(FCH)-free vs a FCH-containing glyceryl trinitrate (NTG, CAS 55-63-0) spray was investigated. Three oral sprays were administered at 24 h intervals to 9 male and 6 female healthy subjects in a double-blind placebo-controlled period-balanced 3-way cross-over study design: treatment NT (FCH-free, NTG-containing spray, dose of 0.8 mg NTG), treatment NR (FCH- and NTG-containing spray, dose of 0.8 mg NTG) and treatment PL (placebo: FCH- and NTG-free spray, dose of 2 puffs). The treatments were administered after suitable preparation and under strict standardisation. Subsequently digital plethysmography (systolic a-wave, dicrotic b-wave and the c-incisura) was monitored for 2 h. After administration of the NTG-containing sprays (NR and NT) the median a-wave increased rapidly, the median c-incisura deepened and the median b-wave rose slightly. The time courses of these changes and those of the resulting b/a- and c/a-ratios were superimposable and clearly distinct from those after PL. On the basis of the analysis of variance of the response variables (Rmin: maximum drop, and A(0-60): the area under the time course during the first hour after dosing) of the c/a-ratio as change from the predosing baseline, the following point estimates and 90% confidence intervals (CI) were calculated for the true ratio of treatments NT/NR: 104.4%, CI: 88.3 to 120.5% for Rmin, and 101.4%, CI: 79.3 to 123.5% for A(0-60).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1910344 TI - [Hemispheric differences in visual recognition of two Kanji characters]. AB - The purpose of the present study was to examine hemispheric differences in visual recognition of two kanji letters. Kanji phrases and nonsense kanji letters were presented unilaterally to the left or right visual hemifield in thirty normal right-handed men by a tachistoscope. The experiments were separated into three conditions; the mixing tasks (ten phrases and ten sets of nonsense letters are presented by mixture), the phase task (twenty phrases are presented), and the nonsense letters task (twenty sets of nonsense letters are presented). Under all conditions, significant right visual hemifield superiorities for the accuracy of recognition of phrase and nonsense letters were observed. PMID- 1910343 TI - Physiologic status at 1-year follow-up of obese women engaged in a supervised conditioning program. AB - A follow-up study was conducted to re-evaluate a group of obese middle-aged women (n = 13), eight of whom had completed an 18-wk supervised (3 d/wk) plus unsupervised (2 d/wk) conditioning intervention program (at least 90 min per day) as the exercise plus diet group; while five of the remainder served as the control group. Each session had included a 25- to 45-min jog/run at intensities between the heart rate (HR) corresponding to lactate threshold (LT) and that slightly above the HR @ LT. During 1 year following the program, the women participated in self-controlled training such as running, aerobic dancing, or jazz dancing 2.6 +/- 1.1 d/wk. Dietary intake averaged approximately 1736 +/- 152 kcal/d at the pre-treatment, 1404 +/- 124 kcal/d at the post-treatment, and 1645 +/- 147 kcal/d 1 year after the post-treatment. Interestingly however, oxygen uptake corresponding to LT (VO2 @ LT), maximal oxygen uptake (VO2max), weight, systolic blood pressure, and the ratio of high-density lipoprotein cholesterol to total cholesterol (HDLC/TC) observed 1 year after the post-treatment were significantly different from the original pre-treatment and/or mid-treatment values. For instance, the significant 42% increase (14.7 +/- 2.4----21.3 +/- 4.2 ml/kg/min) in VO2 @ LT and 18% increase (0.284 +/- 0.106----0.335 +/- 0.093) in HDLC/TC from the pre-test to post-test were maintained throughout the 1-year follow-up period, suggesting no detrimental effect either on a cardiorespiratory fitness factor or on an anti-atherogenic factor. These findings indicate that physiologic status of obese middle-aged women engaged in a conditioning intervention program may not regress to pre-treatment status for at least one year after completion; provided they continue to participate in a 2.6-d/wk self controlled training program with dietary intake of 1600-1700 kcal/d. Another interesting finding was that significant relationships existed between individual changes (delta) in training frequency and individual changes (delta) in physiologic variables (i.e., delta VO2max, delta VO2 @ LT, delta WT, delta fat, and delta HDLC/TC) during the follow-up study. It is concluded that, although the improved physiologic status of obese women can be maintained fairly well during 1 year following the conditioning program; continuation of training (3 d/wk or more) should be critical, either supervised or self-controlled, for successful maintenance of lost weight (8.2 +/- 2.9 kg) and improved fitness. PMID- 1910345 TI - Cardiorespiratory and lactate responses to a 1-hour submaximal running at the lactate threshold. AB - Cardiorespiratory and blood lactate (La) responses to prolonged submaximal running at an intensity relative to lactate threshold (LT) were examined in 15 recreational runners, aged 19 to 32. In test 1 where treadmill speed was progressively incremented by 10-20m/min until exhaustion, oxygen uptake at the LT (VO2 @ LT: 2.34 +/- 0.331/min or 41.6 +/- 5.7 ml/kg/min) and VO2max (3.58 +/- 0.341/min or 63.6 +/- 5.5 ml/kg/min) were measured. In test 2, the subject was required to run on the treadmill for 1 hour at a fixed velocity (Vt) which corresponded to his Vt @ LT. As expected, mean VO2 ranged during the 1-h submaximal running from 2.31 +/- 0.411/min or 63.0 +/- 7.8% VO2max at min 10-20 to 2.52 +/- 0.351/min or 69.2 +/- 6.2% VO2max at min 50-60, both of which were close to VO2 @ LT (65.2 +/- 4.4% VO2max). The slight decrease in blood La was found from min 20 to min 60, and this was accompanied by a parallel decline in respiratory exchange ratio. Shifts in the energy substrate toward a reliance on fat oxidation may occur during the course of 1-h running at Vt @t LT. The small oxygen debt observed after the 1-h running may confirm the assumption that prolonged running at Vt at LT would be performed in an almost fully aerobic steady state. We conclude that prolonged running at Vt @ LT may possibly maximize health-related benefits in the healthy adult. PMID- 1910346 TI - [Functional differentiation of thermoregulation, with particular references to seasonal variation of whole body sweat rate of exercising man]. AB - We investigated the seasonal variation of sweating response during exercise. Four adult healthy men repeated a moderate bicycle exercise (60 watts) in a climatic chamber of an ambient temperature of 30 degrees C (relative humidity, 45%) in winter, spring, summer, and fall. In summer, sweat rate immediately increased as soon as the exercise started, whereas in winter in a few minutes. The mean sweat rate during exercise was significantly different between winter and summer. The transient reduction of the Tsk was observed at the beginning of the exercise in winter. The Tsk decreased in proportion to increasing of sweat rate in each season. Significantly negative correlations were found between sweat rate and the rate of change of Tsk during exercise in each season. The slope and intercept of regression line were significantly different between winter and summer. The index of sweating was made available for the relative value, changing rate against annual mean value of total sweat loss (delta SR, %). The relative value rather than the absolute value (i.e., expressed as g.m-2.h-1) corrected well with skin temperature. It is suggested that the present results may reflect adapted changes in the thermoregulatory mechanisms to seasonal acclimatization. Moreover, the fall in skin temperature during exercise may be not due to increased evaporative cooling, but may be the result of vasoconstriction probably caused by non-thermal factors. PMID- 1910347 TI - [Development of behavior and sex differences in infants; with reference to the formation of sex role]. AB - In order to observe the formation of sex role, an investigation was made on the development of behavior and sex differences in infants aged 1 to 6 at Fukuoka city. The present study consisted of questionnaire on behavior of daily living and breeding, block construction test and coloring a drawing test. The parents instructed their infants to become masculine for males and feminine for females on the basis of traditional view. No sex differences were observed in construction ability of infants aged 4. Favorite colors were different according to sex. PMID- 1910348 TI - Quantitative study of behavioral disturbances in rats exposed to high pressure. AB - When human divers or experimental animals are exposed to high pressure, they develop the High Pressure Neurological Syndrome (HPNS). Male Sprague-Dawley rats were exposed to high pressure in a conventional helium-oxygen breathing mixture to 80 bars. Pressure-induced behavioral motor disturbances including hyperlocomotor activity (HLA), tremor and myoclonia were monitored with a noninvasive piezoelectrical sensor device enabling a without discontinuity long term analysis. New data were obtained on the development of the HPNS behavioral motor disturbances. Indeed, the present results suggest myoclonia would be more sensitive to constant high pressure exposure, while HLA and tremor would be more sensitive to increasing pressure. Moreover, myoclonia were found to occur significantly later in rats which developed epileptic seizures than in other. The present results constitute the quantitative basis of HPNS motor disturbances for future pharmacological pressure experiments. PMID- 1910349 TI - [Practical approach to the discovery of serum markers for infection by hepatitis B virus (HBs antigen or anti HBc antibody). Hypertransaminasemia or the two anomalies in a blood donor]. AB - By now in France HBV seric markers (Ag HBs and Ac HBc) and transaminases level (ALT) screenings are compulsory by law in blood donors. People whose blood donation is discarded should be informed. A clinical, epidemiological and virological survey of such donors is required to differentiate healthy Ag HBs carriers and patients suffering from hepatitis B (who may eventually be treated). Similar guidelines may be recommended for the blood donors presenting high transaminases level without HBV seric markers in order to find a cause for such impaired biochemical tests: overweight, alcohol, drug consumption, auto-immune liver disease, genetic disorder, Non-A, Non-B, Non-C hepatitis.... PMID- 1910350 TI - [Practical approach to the discovery of a positive HIV serology in a blood donor]. PMID- 1910351 TI - [Approach to the discovery of a low hematocrit or hemoglobin level in a blood donor]. PMID- 1910352 TI - [Practical approach to the serodiagnosis of syphilis in a blood donor]. PMID- 1910353 TI - Myelin proteins in aging human brain. AB - Autopsy material of 13 persons who died between 70 and 89 yrs old and of patients who died between 27 and 44 yrs old was studied. White matter of temporal, parietal, and occipital lobes was investigated using histological and biochemical methods. According to results of neuropathological studies, the material of aged patients was divided into two subgroups: (a) brains with vascular changes only and (b) patients with senile atrophy of Alzheimer type. Chemical changes found in all studied brain lobes included a mild decrease in Wolfgram protein content with reciprocal increase in large basic protein content, together with a marked decrease in myelin yield. The abovementioned chemical changes were almost identical whether they were only vascular changes or whether senile atrophy of Alzheimer type was also present. It seems, therefore, that the degeneration of vessels is the decisive factor in the pathogenetic mechanism of myelin lesions in the aged brain. PMID- 1910354 TI - A new model of global postischemic reperfusion in rabbit. AB - An ideal model of global ischemia in rabbits has not yet been developed. The present study describes a new model of global postischemic reperfusion (GPIR) in the rabbit, characterized by lack of systemic hypotension. The experimental procedure involves reversible occlusion of the bilateral internal carotid arteries (ICA) and bilateral external carotid arteries (ECA) for 60 min combined with permanent ligation of bilateral vertebral arteries (VA). This grouping is called 6-artery occlusion (6AO). Sixty minutes after the occlusion, bilateral ICA and bilateral ECA were released for 120 min at which time the experiment was terminated. The results revealed severely depressed EEG activity; Water content of brain tissue increased to 80.33 +/- 1.20% (control 78.28 +/- 0.59%, p less than 0.01); K, Mg, and Zn decreased (p less than 0.05 or p less than 0.01), and were negatively correlated with tissue water content. Na increased (p less than 0.05) and correlated with water content of brain. No significant changes were observed in lipid peroxide (LPO) levels, but the activity of superoxide dismutase (SOD) of brain tissue decreased (p less than 0.01), and was negatively correlated with water content (r = -0.5808, p less than 0.05). These results were compared with those obtained with the model of 4-artery (bilateral common carotid arteries (CCA) and VA) occlusion (4AO) and suggested that the brain damage be more severe with 6AO than with 4AO. PMID- 1910355 TI - Taurine release from brain slices in thioacetamide-induced hepatic encephalopathy in rats. AB - The possible involvement of taurine in the pathogenesis of hepatic encephalopathy was studied in rats injected with thioacetamide. Spontaneous release of exogenous labeled taurine was not affected in any brain area studied, but the potassium stimulated release was enhanced in the striatum in thioacetamide-treated rats. High concentrations of ammonium ions also evoked greater release of taurine from striatal slices in rats with thioacetamide-induced hepatic encephalopathy. PMID- 1910356 TI - Changes in lipid metabolites and enzymes in rat brain due to ischemia and recirculation. AB - Thirty and 60-min ischemic insults resulted in an increase in free fatty acid and 1,2- diacylglycerol contents of rat forebrain. No significant changes were detected in phospholipids except phosphatidylinositol 4-monophosphate and phosphatidylinositol 4,5-bisphosphate during ischemic insult. Phosphatidylinositol 4-monohosphate and phosphatidylinositol 4,5-bisphosphate contents decreased during ischemia. Although the increase in free fatty acid contents continued, 1,2-diacylglycerol did not show further increase after 30-min ischemia. These results suggest that there may be another pathway for the accumulation of free fatty acids in addition to phospholipase C coupled to di- and monoacylglycerol lipase. Free fatty acid and 1,2-diacylglycerol contents increased transiently and thereafter decreased to control levels within 90 min after postischemic recirculation. The decrease in arachidonic acid content preceded those of other FFA. Phosphatidylinositol 4-monophosphate and phosphatidylinositol 4,5-bisphosphate contents gradually increased after the initiation of recirculation in ischemic brains. Lysophosphatidylcholine decreased gradually after temporary increase during 15 and 5-min recirculations in 30 and 60-min ischemic groups. Phospholipase A, phospholipase C, and di- and monoacylglycerol lipase activities did not show significant changes during entire course of recirculation. Total activities of lysophospholipase and acylation enzymes of lysophospholipid demonstrated 1.5-and 2.2-fold increase during 30-min recirculation. PMID- 1910357 TI - The metabolic fate of [3H-methyl]choline in cultured human neuroblastoma cell lines, LA-N-1 and LA-N-2. AB - The conversion of choline in cultures of the human neuroblastoma cell lines, LA-N 1 and LA-N-2 cells, was investigated in order to identify potential precursors in acetylcholine (AcCho) synthesis. LA-N-1, a catecholaminergic and LA-N-2, a cholinergic, cell line were incubated with [3H-methyl]choline (Cho) for varying periods of time up to 72 h. The radioactivity present in lipids and water-soluble metabolites increased linearly up to 24 h in both cell lines. Approximately 20% of the radioactivity associated with the water-soluble metabolites in both control (untreated) and retinoic acid-induced differentiated (RA-treated cells) LA-N-2 cells was present as Cho and AcCho. There was no detectable AcCho in the catecholaminergic cell line, LA-N-1. The untreated and RA-treated LA-N-1 and LA-N 2 cells were labeled for 24 h with [3H-methyl]Cho, followed by a chase in growth medium containing 100 microM unlabeled choline. The distribution of radioactivity in the LA-N-2 cells was 6-10% of AcCho, 84-89% as phosphocholine (PCho), 1-3% as glycerophosphocholine (GroPCho), and 2-4% as Cho. The distribution of radioactivity in the LA-N-1 cells was similar except for the absence of AcCho. The distribution of radioactivity in the culture medium of LA-N-1 cells was 70 80% as Cho, 20-30% as PCho, and 1-3% as GroPCho. In contrast, the radioactivity was equally distributed between Cho (50%) and PCho (50%), with only 1-3% as GroPCho in the medium of LA-N-2 cells. PMID- 1910358 TI - Early clinical neurochemistry of CNS-active drugs. Bromides. AB - The use of bromides in medicine dates back to the beginning of the 19th century. The salts were used in neurological and mental diseases, particularly in epilepsy, up until their partial replacement by phenobarbital and ultimate displacement by dilantin. This article reviews the analytical methodology as it developed historically, and traces the application of chemical analysis of body fluids to monitoring for bromide toxicity (bromism) and then to investigation of the blood-brain barrier in various disorders of the central nervous system. PMID- 1910359 TI - Plasminogen activator inhibitor in acute stroke. AB - Plasminogen activator inhibitor activity was determined in patients (26 men, 6 women) with acute ischemic stroke (n = 28) and transient ischemic attack (TIA) (n = 4). Age-matched patients (22 men, 10 women) with various nonvascular neurologic diseases served as controls. Plasma levels of plasminogen activator inhibitor activity were significantly higher in the stroke group (p less than 0.003). Serum triglycerides and plasminogen activator inhibitor activity correlated positively in the stroke group (p less than 0.03) and in controls (p less than 0.0001). Our data suggest a possible involvement of plasminogen activator inhibitor activity in the pathophysiology of stroke. PMID- 1910360 TI - Decrease in blood histamine in drug-treated parkinsonian patients. AB - Blood histamine and serum histaminase activity were determined in a group of patients with Parkinson disease (PD) and in a group of healthy controls. Untreated PD patients present significantly higher blood histamine than normal controls. Therapy with L-dopa + cardidopa results in a significant decrease in blood histamine. This decrease becomes more accentuated when anticholinergics are added to this therapy. No significant changes were detected in plasma histaminase. The authors suggest, as a hypothesis, that the CNS contributes to blood histamine concentration and that its rise is the result of increased neuronal destruction. PMID- 1910361 TI - Ganglioside levels in hypoxic brains from neonatal and premature infants. AB - In this study, 13 cases of newborn term-gestational infants and six cases of premature infants who died of hypoxia were selected for the determination of ganglioside levels in several regions of brains obtained at autopsy. Cases were divided into three groups according to the hypoxic interval and gestational age: Group A, six cases of newborn infants. The average time of hypoxia was 6.4 h. Group B, seven cases of newborn infants. The average time of hypoxia was about 71 h. Group C, six cases of premature infants. The average hypoxia time was 34.7 h. Frontal cortex, forebrain, hippocampus, and parahippocampal gyrus and cerebellum of each brain were examined. The method of Ladisch and Gillard (1985) was used to purify and quantify gangliosides. The results showed that total gangliosides decreased significantly in three regions of cerebral hemispheres of group B and in four brain regions of group C, as compared with group A (p less than 0.01). The amount of gangliosides in frontal cortex in group B was lower than in group C (p less than 0.01). The four major gangliosides (GM1, GD1a, GD1b, and GT1b) were all reduced in cerebral hemispheres of group B and C. In hypoxic brains, the percentage of gangliosides also showed some alterations. There was less GD1a in the cerebral hemispheres of group B and the frontal cortex of group C. The amount of GD1b was also less in the frontal cortex and forebrain of group B than in group A or C. The results suggest that severe hypoxia might cause decreases in brain gangliosides that correlate to the severity of brain damage. PMID- 1910363 TI - [Open or closed technique of tympanoplasty. Comments on saving the posterior wall of the auditory canal]. PMID- 1910362 TI - Changes in brain calpain activity as a result of in vitro ischemia and pH alterations. AB - Calpains and calpastatin in the brain of the rabbit were examined in experimental situations that could mimic some features of brain ischemia. Incubations of bisected brains in saline at 39 degrees C for 0.5, 1, or 1.5 h resulted in a decreased calpain I activity in the cytosol and in an increased hydrophobicity of cytosolic calpain II activity. Incubation of brain homogenates at different pH levels demonstrated an almost-complete transfer of calpains from the cytoplasmic compartment to the membranes when pH was lowered from 6 to 5. At pH values lower than 5, the total calpain activity (soluble plus membrane-bound) markedly decreased. No significant changes of calpastatin activity or its subcellular distribution was found following incubation of the homogenates at different pH levels. PMID- 1910364 TI - [Fibrinolytic therapy in sudden deafness with recombinant tissue-type plasminogen activator. Hemorheologic and therapeutic effects]. AB - In the course of a pilot study, the effects of fibrinolysis treatment with rt-PA (Actilyse, Thomae, Biberach; 100 mg) on the recovery of hearing and hemorheologic parameters were investigated in 12 patients suffering from sudden hearing loss. The authors' approach was based on two considerations, (1) the possibility that, in cases of sudden hearing loss, the oxygen supply to the cochlea is totally or partially blocked by a microthrombus which could be dissolved by rt-PA and (2) the fact that lysis markedly improves the flow characteristics of the blood (as has been demonstrated in studies with streptokinase and urokinase). This human plasminogen activator, produced by genetic engineering, is superior (also in terms of possible side-effects) to other lysin enzyme preparations (streptokinase, urokinase) because of its highly selective effects on thrombi (low activation of plasma plasminogen) and its short half-life (approx. 4 min). In nine of 12 patients, the treatment brought about a marked improvement in hearing or its complete restitution (three of the patients has initially been deaf in the affected ear). In the three nonresponders there was serologic evidence of an inner-ear infection (neuroborreliosis, cytomegaly, influenza B). The most interesting rheologic effect was the reduction of plasma viscosity (average decrease about 18%), since such a reduction cannot be attained with other, comparable rheologic measures (isovolemic or hypervolemic hemodilution). In spite of the convincing hemorheologic effects, fibrinolysis cannot yet be recommended as treatment for sudden hearing loss. Further studies have still to be done on spontaneous healing, the effects of hemorheologic measures on the blood circulation of the inner ear, and on the oxygen requirements of the ear affected by hearing loss. PMID- 1910365 TI - [Initiation of therapy and type of therapy in sudden deafness: an observation including the medico-legal viewpoint]. AB - In the literature, the chance of success of delayed treatment of sudden deafness is variously assessed. A high degree of remission can be observed when treatment is begun within 3 days. Medicolegal problems with respect to the start of therapy, and the nature of treatment are discussed. PMID- 1910366 TI - [Computer-assisted phonetography as a diagnostic aid in functional dysphonia]. AB - A total of 160 voice-trained and untrained subjects with functional dysphonia were given a "clinical rating" according to their clinical findings. This was a certain value on a scale that recorded the degree of functional voice disorder ranging from a marked hypofunction to an extreme hyperfunction. The phonetograms of these patients were approximated by ellipses, whereby the definition and quantitative recording of several phonetogram parameters were rendered possible. By means of a linear combination of phonetogram parameters, a "calculated assessment" was obtained for each patient that was expected to tally with the "clinical rating". This paper demonstrates that a graduation of the dysphonic clinical picture with regard to the presence of hypofunctional or hyperfunctional components is possible via computerised phonetogram evaluation. In this case, the "calculated assessments" for both male and female singers and non-singers must be computed using different linear combinations. The method can be introduced as a supplementary diagnostic procedure in the diagnosis of functional dysphonia. PMID- 1910367 TI - [Diagnosis and therapy of aggressive fibromatosis (extra-abdominal desmoid) in the head and neck area]. AB - Desmoid tumours (extraabdominal desmoids, aggressive fibromatosis) are rare connective tissue tumours, that grow infiltratively and destructively. The analysis of the course of disease in three patients suffering from desmoid tumours in the head and neck region (regio submandibularis, regio parotidea, parapharyngeal space) confirmed the data in literature that painless swelling and dysfunction are the first non-specific signs of the disease. Morphologically reactive fibromatosis and fibrosarcoma should be considered (amongst others) in differential diagnosis. CT and MR scans are useful in determining the extent of the tumours and help to distinguish the tumour from nerves, vessels and bone. Surgery is the therapy of choice in the head and neck region. Primary surgery was performed in our patients. Due to recurrences two of our patients have been operated on several times including major plastic reconstructive surgery. One patient died three and a half years after primary treatment due to sarcomatous degeneration. A large parapharyngeal recurrence was successfully reduced by percutaneous radiation therapy in our second patient. Follow-up of our third patient was NAD 15 months after resection of a large parapharyngeal/mediastinal process including blocking of two cervical vertebrae. Summing up, desmoid tumours are rare connective tissue tumours in the head and neck region with a destructive biological behaviour similar to malignant tumours and a high recurrence rate. Surgery is the treatment of choice. In recurrences or if the tumour is not properly resectable, radiation must be considered, whereas the chemotherapeutical approach is not yet well established. PMID- 1910368 TI - [Histologic study of the effect of postoperative irradiation on free transplanted jejunal segments]. AB - After the reconstruction of defects resulting from the resection of advanced tumors from the upper aerodigestive tract using free microvascular anastomized jejunum, the autotransplant is influenced by local radiotherapy (cumulative dose 50-70 Gray). Biopsies were taken from 15 patients, stained with haemotoxilin eosin and Giemsa and compared by means of light microscopy with jejunum taken at the time of transplantation. It was possible to observe a widened mucosal and submucosal space two to three months after radiotherapy, similar to the clinical impression of a radiogenic enteritis. The villi were flat and shortened with no or slight epithelial lesions. Additionally, it was possible to observe an inflammatory infiltration consisting mainly of neutrophilic granulocytes, edemas, and telangiectases. The latter were also evident in nonirradiated autotransplanted jejunum and are therefore not only caused by irradiation. One year after radiotherapy the mucosal membrane was atrophic. Fibrosis was to be seen in the lamina propria, accompanied by widened muscularis mucosae. The submucosal space was also widened and fibrotic to a varying degree. It was possible to detect varying stages of alteration in the vascular system up to a complete obliteration. After two years, changes were more pronounced. At no time could any alteration in the nervous system of the plexus submucosus be observed. All of these changes have to be interpreted as a consequence of irradiation. However, lubrication of the mucosal surface and the motility of the transplant are not altered severely by irradiation and therefore the desired functions of the free transplanted jejunal grafts, such as swallowing and phonation, are carried out sufficiently.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1910369 TI - [Hyperbaric oxygen in the treatment of osteoradionecrosis of the mandible]. AB - Osteoradionecrosis (ORN) of the mandible is one of the most dreaded complications in the treatment of cancer of the head and neck. If conservative and surgical treatment have not been successful, very often the only remaining solution is surgical intervention into the bone continuity of the mandible. In a group of eight patients suffering from ORN of the horizontal ramus of the lower jaw we gathered first experiences with hyperbaric oxygen therapy in combination with an operation to preserve the bone continuity (debridement of the bone and closing of the soft tissues). Hyperbaric oxygen was given during a time span of 13 to 52 hours (average: 36 hours). It was only with those two patients who received more than 50 hours of hyperbaric oxygen therapy that we achieved our aim of "total recovery from ORN of the mandible while saving its bone continuity". In one case where there was no clinically manifest recidivation of the tumour, the tumour showed rapid growth under hyperbaric oxygen therapy. In three cases partial resection of the mandible had to be performed without reconstruction for cure of ORN. Despite the loss of bone continuity these patients are only slightly cosmetically impaired and nutrition causes no problems. In two patients ORN still exists. On the basis of our first experiences with a small group of patients and in accordance with various publications, we conclude that hyperbaric oxygen therapy is a significant adjunct in the treatment of the mandible if a well founded diagnosis is established and if it is followed by a well-adjusted therapy. PMID- 1910370 TI - [Sialadenosis caused by long-term valproate medication]. AB - A case of a valproate-induced sialadenosis is presented. The aetiology and pathomechanism of drug-related sialadenosis are discussed. The antiepileptic valproate is now added to the list of drugs inducing sialadenosis. PMID- 1910371 TI - [How I do it. On nomenclature of transplantations in otorhinolaryngology]. PMID- 1910373 TI - [Stapes dislocation and opening in the inner ear due to tympanoplasty]. AB - During tympanoplasty, the stapes is often exposed to considerable manipulations, i.e. the dissection of cholesteatoma matrix from the oval window niche or the insertion of a prosthesis for ossicular chain reconstruction. Too much strain may rupture the annular ligament resulting in an opening of the inner ear. Furthermore it is conceivable that microperilymphatic fistulas, which remain undetected, may develop prior to a visible luxation of the stapes. Therefore, temporal bone experiments with definite manipulations on the stapes were performed to study the rupturing strength of the annular ligament. Increasing the pressure of the methylene blue dyed perilymphatic fluid facilitated the detection of even smallest ruptures. A leakage occurs only in case of a complete rupture of all fibres. Further findings of clinical interest, gained from these experiments with different directions of stapedial manipulation, are discussed. PMID- 1910372 TI - [Microendoscopy of the Eustachian tube and the middle ear. Indications and clinical application]. AB - Progressive miniaturization of flexible fibreoptic systems has made it possible for the first time to perform atraumatic endoscopy of the Eustachian tube and tympanic cavity with the ear drum intact. With the aid of special actively steerable microcatheters, flexible fibrescopes having outer diameters of 350 to 650 microns are inserted into the opening of the naso-pharyngeal tube and advanced into the tympanic cavity under direct visual control. This new technique is indicated for any disturbance of sound conduction and in those sensorineural hearing disorders in which direct inspection of the middle ear cavity can provide information on the pathogenesis of the disturbance. In the future it may thus replace purely diagnostic tympanoscopy. In combination with fibre-delivery laser systems, this new method forms the basis of "microendoscopically controlled laser surgery" of pathological changes within this anatomical region. PMID- 1910374 TI - [Results of tympanoplasty following application of cartilage-perichondrium transplants for tympanic membrane substitution under unfavorable circumstances]. AB - From a series of 2335 cases of ear surgery over a five-year period, the author reports on 550 cases where perichondrium cartilage from the tragus or concha was used as transplant material. Two different surgical techniques were employed. The postoperative gain in hearing and the overall incorporation rate are presented. PMID- 1910375 TI - [Welding spark injuries of the ear. Observations of personal case material]. AB - 25 cases of tympanic welding spark injuries of the years 1959-1989 are reported. Early results and late sequelae after conservative therapy, immediate and interval operation are described and discussed. Regarding the tendency of tympanic defects to enlarge after thermal injuries despite conservative and early operative therapy, secondary seal by tympanoplasty is recommended. Even then, however, the rate of residual and recurring perforations must be reckoned as being higher than after tympanoplasty in comparable defects of other origin, due to the inferior nutritive supply owing to the extended scar caused by burning. On the other hand, the rate of inner ear traumatisation with 12% directly after welding injury and with 4% remaining impairment of hearing, is low. PMID- 1910376 TI - [Bifenestration--a hearing-improving operation in severe ear malformations]. AB - Bifenestration as an operation for hearing improvement is described in a case of congenital absence of the oval and round window. Besides the classical fenestration of the horizontal semicircular duct, an artificial round window was performed in the middle ear. Due to the acoustic resonance of the mastoid cavity, the resulting conductive loss in the higher frequencies was only 20-30 dB. PMID- 1910377 TI - [Evoked oto-acoustic emissions (EOE) as screening method in infants]. AB - The authors consider the problems of the early diagnosis of paediatric hypoacusis, presenting a study done on twenty audiological high risk children that were subjected to audiometric screening by delayed cochlear otoacoustic emissions (EOE) and brainstem auditory evoked potentials (BEAPs). Eighteen of twenty children that were examined were normal, while two had bilateral sensorineural hearing loss. EOE were evoked in all patients that presented normal BAEP thresholds, while they were absent in deaf subjects. Evoked otoacoustic emissions research allows us to identify two groups of subjects: those with normal EOE who can be considered normal hearing subjects, and those without EOE who may present a disturbed auditory system. Nevertheless, EOE testing does not allow us to judge the type of hearing loss. The time for EOE testing is approximately five minutes for each subject. On the grounds of their experience, the authors conclude that EOE testing represents a useful and reliable test which differentiates normal auditory function subjects from hypoacoustic ones. Compared to other techniques used in audiological paediatric diagnosis, such as reactometry, BOEL test and Crib. O. Gram, which present the possibility of false positive and false negative results, and BSERA, which even if reliable, must be limited to few selected audiological high-risk subjects, EOE is easy to implement and readily available. Major limitations of this technique seem to be the possibility of false positives, and the impossibility to specify localisation and type of the hearing loss by EOE only. PMID- 1910378 TI - [A brief history of hearing research. III. Microscopic anatomy]. AB - The present review provides merely a glimpse of the vast field of modern anatomy of the ear, which began with the introduction of the light microscope and histological techniques. Owing to the poor accessibility and small size of the inner ear, the investigation of its structure was highly dependent on the development of modern histological techniques, i.e. fixation, embedding, sectioning and staining of tissue, which took place in the 19th century. In 1824 Huschke discovered the papilla spiralis acoustica and in 1851 Corti described the structure of the sensory epithelium of the inner ear, and also detected the outer hair cells. A little later Deiters also found the inner hair cells, while Leydig discovered the stereocilia on the hair cells. In 1863 Hensen showed that the hair cells were provided with nerve endings, but it was Retzius who proved that the nerve fibres terminate at the basal end of the hair cells. He concluded from his studies that the hair cells are the actual receptors of the organ of hearing. Hensen, Retzius and Held provided morphometric data of the cochlea which are still largely valid today. In 1926 Held managed to isolate single hair cells. He also described two different types of nerve fibre in the cochlea. In 1926, Kolmer was the first to propose that apart from afferent nerve fibres there might also be an efferent innervation of the cochlea. In 1942 this was confirmed by Rasmussen. In animal experiments, he and others demonstrated the efferent nature of the olivo-cochlear bundle by dividing the nerve, which subsequently showed secondary descending degeneration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1910379 TI - [HMPAO-SPECT during carotid artery compression (Matas test) in the evaluation of cervical tumor surgery with potential carotid involvement]. AB - For planning the surgical approach in patients with head and neck tumours and extensive cervical metastasis the evaluation of possible vascular involvement is necessary. If the carotid artery is suspected to be infiltrated by the tumour masses its resection or plastic substitute becomes sometimes inevitable. For evaluation of the collateral brain perfusion before a possibly necessary carotid resection we examined 10 patients with neck tumours performing the Matas-Test combined with HMPAO Single-Photon-Emission-Computed-Tomography. During ultrasound controlled manual compression of the involved common carotid artery 99mTc labelled HMPAO was injected. The SPECT demonstrated the brain perfusion during the carotid compression time period. 6 patients showed a decreased perfusion of the affected hemisphere with - as far as obtained - normal baseline SPECT-results and balloon occlusion tests. 2 of these patients underwent a carotid artery resection, one of the common carotid artery and one of the internal carotid artery. One patient had a significant perfusion deficit in the SPECT but no pathologic findings in angiography and balloon occlusion test. He suffered from hemiparesis postoperatively. The other patient showed preoperatively a minor decrease in perfusion and had no neurological defects postoperatively. Our findings show that the Matas-Test combined with HMPAO-SPECT is a valuable tool for the preoperative evaluation of the collateral brain perfusion. This technique is not invasive and can be performed in every nuclear medicine department with an ECT camera. The HMPAO-SPECT during carotid compression can add useful information or even replace angiography and the balloon occlusion test. PMID- 1910380 TI - [Transcranial Doppler ultrasonography in head and neck tumors]. AB - Transcranial Doppler ultrasound (TCD) recording is a non-invasive diagnostic procedure for the evaluation of the cerebral collateral flow in patients, in whom therapeutic ligation or resection of the common and/or internal carotid artery is planned. Patients are first examined under resting conditions, and then under manual compression of the ipsilateral carotid artery. Since January 1989, 31 ENT and neurosurgical patients have been examined. In all patients an immediate decrease in flow velocity in the middle cerebral artery (mca) of about 25% to 90% was recorded. In 42.8% of the patients the mca flow velocity reached 90% or more of its value under normal conditions within a short period. In 29% of the patients the mca flow velocity under manual compression of the carotid artery remained under 50% of its original value. In 68% of the cases TCD with manual compression of the carotid artery showed reliable results for the function of cerebral collateralisation as a prognostic factor of the risk of ischaemia due to haemodynamic changes after carotid ligation. In these cases no further examination of the cerebral collateral flow conditions was needed. The method is inexpensive, reproducible, and in comparison with cerebral angiography, convenient and non-hazardous for the patient. PMID- 1910381 TI - [Connector technology: development of simple rapid transfer of free microsurgical tissue flaps in the head and neck region]. AB - The aim of this research program was to develop vessel connectors to replace the difficult microsurgical suture, which could be implanted quickly, safely and without any special training. Three types of connectors were developed specially for the anatomical features of the head and neck region: miniconnectors, stick connections with vascular prosthesis, and interposition connectors. The development of the model, the biomechanical tests on the in-vitro system comprising a free, muscular, porcine latissimus-dorsi flap, and the in-vivo tests involving implantation of the connectors in vessels of rats, rabbits, dogs and pigs are outlined. The results are compared with those obtained with conventional microsurgical interrupted sutures.--The indications for these three different types of connector are determined by the diameter and quality of the vessels (vein, artery). PMID- 1910382 TI - [Closure of septum perforation using an individual obturator]. AB - Alternatively to operative procedures we present the production of an individually formed septal obturator to close an iatrogenic septal perforation. After taking the impression from the perforation the obturator was casted out of silicone via a plaster mould. This possibility can help in those cases where septal perforation cannot be closed by operative procedures. PMID- 1910383 TI - [Epidermal growth factor (EGF) receptors in squamous cell carcinoma of the head and neck region]. AB - The expression of epidermal growth factor receptors (EGFR) has been studied immunohistochemically in 66 squamous cell carcinomas of the head and neck. All investigated tumours overexpressed EGFR showing a homogenous distribution pattern. Pretreatment of tumours (eg. chemotherapy or radiation) did not influence this result. Our findings indicate that EGFR expression is not strongly correlated to proliferative activity, and is not suited to be used as a prognostic marker. It is possible that the observed overexpression of EGFR in squamous cell carcinomas of head and neck can be used as a target for ligand complexed drugs. PMID- 1910384 TI - [High-caloric nutrition in radiochemotherapy, nasogastric tube and parenteral nutrition versus PEG (percutaneous endoscopic controlled gastrostomy)]. AB - The advantages and problems of different types of artificial feeding are discussed. For patients needing long-term nutritional support, we see the following special advantages of PEG: physiological enteral nutrition with an only small risk of tube dislocation, no additional handicap of the natural swallowing procedure and without stigmatizing the patient by an external visible tube (Tab. 3). To help to spread this method of artificial feeding for the benefit of the patient, this article gives some informations on how to cope with the problems that might occur when using PEG (for example: a diet plan for building up the tube food nutrition (Tab. 4). PMID- 1910385 TI - [Kimura disease--2 case reports]. AB - Two histologically confirmed cases of Kimura's disease are reported in the present article. Emphasis is placed on the clinical symptoms in conjunction with the histological picture. Recent studies in the literature are discussed with respect to differential diagnosis, etiology and therapy. In all ENT-tumours of unknown origin this relatively uncommon disease should also be considered. PMID- 1910386 TI - [Intraoperative BAEP and adenoidectomy in the young child with delayed language development]. PMID- 1910387 TI - Ions modify the strength of interaction of diquat and paraquat with some proteins and cellulose. AB - The interaction of the bipyridylium herbicides diquat and paraquat with the proteins gliadin and human serum albumin (HSA) as well as with cellulose and the effect of various ions on the strength of interaction were studied by charge transfer chromatography. Both compound showed very similar behaviour. The ions decreased in each case the strength of interaction, the effect depended nonlinearly on the ion concentration and was of saturation character. Gliadin showed the weakest interaction. HSA binds the bipyridylium compounds in an ion dependent manner, the strength of interaction is higher than that of cellulose at higher ion concentration. This finding indicates an ion-mediated interaction of unknown character between the bipyridylium herbicides and HSA. PMID- 1910388 TI - Slit scan flow cytometry of isolated chromosomes following fluorescence hybridization: an approach of online screening for specific chromosomes and chromosome translocations. AB - The recently developed methods of non radioactive in situ hybridization of chromosomes offer new aspects for chromosome analysis. Fluorescent labelling of hybridized chromosomes or chromosomal subregions allows to facilitate considerably the detection of specific chromosomal abnormalities. For many biomedical applications (e.g. biological dosimetry in the low dose range), a fast scoring for aberrations (e.g. dicentrics or translocations) in required. Here, we present an approach depending on fluorescence in situ hybridization of isolated suspension chromosomes that indicates the feasibility of a rapid screening for specific chromosomes or translocations by slit scan flow cytometry. Chromosomes of a Chinese hamster x human hybrid cell line were hybridized in suspension with biotinylated human genomic DNA. This DNA was decorated with FITC by a double antibody system against biotin. For flow cytometry the chromosomes were stabilized with ethanol and counterstained with DAPI or propidium iodide (PI). An experimental data set of several hundred double profiles was obtained by two parameter slit scan flow cytometry and evaluated automatically. The evaluation algorithm developed allowed a classification of chromosomes according to the number of centromeres and their chromosomal positions in less than 1 msec per individual profile. Approximately 20% of the measured DAPI profiles showed a bimodal distribution with a significant centromeric dip indicating a "normal" chromosomal morphology and a correct alignment in the flow system. In many cases, profiles of a "normal" bimodal fluorescence distribution of the DNA stain (DAPI, PI) were correlated with a "normal" FITC profile. Due to their centromeric indices these profiles agreed well to the expected human chromosomes of the cell line. In some cases of "normal" DAPI (PI) profiles, "aberrant" FITC profiles were observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1910389 TI - The need for unity in the biomedical research community. AB - The author provides a perspective on how basic scientists view contemporary issues of biomedical research funding by discussing five topics of concern to the biomedical research community and the need for that community to form a new consensus as the basis for new approaches to legislative efforts in Congress and communication with the public. The topics are (1) the reasons scientific societies became active in legislative efforts in Congress, (2) the reasons there was initial friction between these societies and other institutions in the biomedical research community, (3) the history of the founding of a biomedical research community, (3) the history of the founding of a biomedical research caucus in the House of Representatives, (4) the effects of the Institute of Medicine's recent report on funding health sciences research, and (5) the weakness of the present institutional coalition. The author proposes specific steps to develop a more unified approach to achieve a common biomedical research agenda. PMID- 1910390 TI - Assessing the past and planning the future to ensure support for biomedical research. AB - The author notes the current extraordinary excitement and opportunity in biomedical research that, oddly, exist within a context of economic constraint for researchers. Also, there is much negative publicity about biomedical science that threatens efforts to obtain adequate funding and responsible handling of science policy in an era where there is relatively little money available for research. The author reviews past instances of damaging public disunity and squabbles by groups in the biomedical research community and then proposes various policy guidelines and strategies to best ensure adequate research funding in the future. For such policies and guidelines to be effective, he stresses the necessity of efforts to heal the past divisions within the biomedical research community and to present a united position that is clear and understandable to Congress and others. PMID- 1910391 TI - Observations from the AAMC advisory panel on biomedical research. AB - The author gives a brief history of the events that led to the establishment of the Association of American Medical Colleges (AAMC) Advisory Panel on Biomedical Research, describes some of its early activities, and discusses some of the issues that the biomedical research community is facing. Specifically, he describes how the competition for research funding that became particularly intense in 1989-90 eroded the well-orchestrated coalition approach to appropriations that had been the norm. Another disturbing development was a growing tension between research faculty and the administrators of their institutions. To address these problems, the author, under the aegis of the AAMC, convened a series of workshops during the summer of 1990 to provide a forum for airing concerns and allowing different groups to become aware of each other's positions and perceptions. These workshops were quite useful and helped in framing some important issues. Also deriving from the workshops was the recognition that a continuing advisory group on research policy was needed; thus the AAMC advisory panel was created. The author describes its unusual characteristics and its importance. Subcommittees were later established to facilitate the effectiveness of the panel. Early in the panel's deliberations it became clear that it was important to bring into the meeting various knowledgeable individuals to educate and interact with panel members. The author concludes by surveying the larger picture of the public's eroding confidence in research universities and higher education in general, the punitive environment that this has created in Congress, the increasingly harsh economic situation, and what these conditions may portend for future research funding. PMID- 1910392 TI - Sensitizing residents to moral issues by case discussions. PMID- 1910393 TI - Structural informatics and its applications in medicine and biology. PMID- 1910394 TI - A computer conference format for teaching medical ethics. PMID- 1910395 TI - The lady on the track. PMID- 1910396 TI - Healthy people 2000: the challenge to academic medicine. PMID- 1910397 TI - Stimulating medical education research through small grants. PMID- 1910398 TI - Ten years of a residency training committee. PMID- 1910399 TI - Teaching autopsy teachers. PMID- 1910400 TI - Minority student admissions. PMID- 1910401 TI - Selecting medical students for the 1990s. PMID- 1910402 TI - Dean's letters. PMID- 1910403 TI - The characteristics of early diagnostic hypotheses generated by physicians (experts) and students (novices) at one medical school. AB - How hypotheses generated at the outset of a physician-patient encounter influence the physician's diagnostic reasoning has received relatively little attention in the literature. Yet, this activity modulates the efficiency and accuracy of the diagnostic process. The authors proposed the theory that physicians (experts) would generate less specific initial diagnostic hypotheses than would students (novices). In 1988 and 1989, the hypotheses generated by 32 practicing physicians and 39 third-year medical students at one medical school were analyzed for number, specificity, and breadth (i.e., range) of diagnoses, and for differences between those generated by the physicians and by the students. The hypotheses were formulated on the basis of the initially available data--chief complaint and its duration, and basic demographic descriptions--from patients in three clinical scenarios. Compared with the physicians, the students generated significantly more hypotheses and significantly more specific hypotheses. There was no significant difference between the groups in the breadths of the hypotheses they selected, that is, the numbers of broad categories of diagnosis covered by individuals' hypotheses. PMID- 1910404 TI - How completely internal medicine residents at a New York State teaching hospital met the expectations of a credentialing protocol. AB - The authors conducted a two-year prospective study (1988-1990) to determine whether internal medicine residents at a multi-facility teaching hospital in New York State could meet the expectations of a formal credentialing protocol and receive independent privileges in a timely manner. The study group consisted of 38 first-year residents separated into two subgroups. Subgroup I, seven categorical and 11 preliminary residents, entered the residency program July 1, 1988; subgroup II, seven categorical and 13 preliminary residents, joined the residency July 1, 1989. During the first three months of the 1988-89 academic year, subgroup I showed minimal compliance, obtaining only 11% of the total privileges available. However, subgroup II, working under a protocol that underwent major revisions related to monitoring the credentialing process, showed significant improvement, with 90% of all required privileges credentialed within the first quarter of 1989-90. The findings suggest that a minimal rate of residents' compliance can be improved dramatically by the development of a structured protocol that includes stringent monitoring of the entire credentialing process and formal, regular feedback to the housestaff regarding their progress. PMID- 1910405 TI - Effects of using two or more standardized patients to simulate the same case on case means and case failure rates. AB - The effects of using two or more standardized patients (multiple SPs) to simulate the same case in a performance-based examination were studied at the case level by comparing case means and case failure rates for multiple SPs simulating the same case, using data from the classes of 1988, 1989, and 1990 at the Southern Illinois University School of Medicine. For total scores and scores on the students' written answers, the effects on means and failure rates were negligible and could be explained as due to sampling error. For scores on the checklists completed by the SPs, there were more significant differences than would be expected by chance alone, even though the number of significant differences was relatively small. The results demonstrate a need for caution in the interpretation of scores obtained from a case checklist completed by multiple SPs, particularly in regard to making pass-fail decisions. PMID- 1910406 TI - Pre-employment drug testing of housestaff physicians at a large urban hospital. AB - In an effort to address drug use and abuse among physicians beginning their graduate medical education. The Presbyterian Hospital at Columbia-Presbyterian Medical Center began a pre-employment drug testing program for housestaff physicians in 1987. Between 1987 and 1990, each of the 791 housestaff physicians beginning training at the hospital received a pre-employment urine toxicology examination. Despite the limitations of pre-employment drug testing, the program did identify two physicians who tested positive for illegal drugs. Based upon their test results and individual clinical evaluations, both physicians were denied a clinical appointment at the hospital. Their clinical training was temporarily interrupted while they received indicated treatment. The author suggests the main value of the program is to provide a focus for addressing issues related to substance abuse during graduate medical education. PMID- 1910407 TI - Impact of an ambulatory care clerkship on the attitudes of students from five classes (1985-1989) toward primary care. AB - This study was designed to evaluate the effects of a required ambulatory care clerkship during the fourth year of medical school on the students' knowledge of primary care medicine and their subsequent career choices. A questionnaire was mailed to the graduates of the Albert Einstein College of Medicine classes of 1985-1989. Fifty-six percent (408) of the questionnaires were returned. An average of 74% of the respondents answered yes to six items that asked whether the clerkship had successfully introduced them to basic concepts and practices of outpatient medicine (range from 58% to 93%, depending on the item). In addition, 90% reported that the clerkship had enhanced their understanding of primary care medicine, while 41% indicated that the rotation had wholly or partially influenced their career choices. The survey findings suggest that exposure to outpatient medicine during medical school plays an important role in facilitating students' knowledge of primary care medicine and influencing their career choices. PMID- 1910408 TI - Ethical principles contained in currently professed medical oaths. AB - This study analyzed the pledges received from all U.S. medical schools accredited in 1989 by the Liaison Committee on Medical Education of both the Association of American Medical Colleges and the American Medical Association to determine what pledges were affirmed and what ethical principles they contained. The Oath of Hippocrates was the most frequently affirmed pledge (the wording of which was used by 60 schools). Few oaths clearly demonstrated respect for patients' autonomy. The principle of veracity was not evident in any oath. However, nonmaleficence, beneficence, and justice were evident in half of the pledges, and confidentiality was included in three-fourths of them. The authors conclude that the medical oaths failed to address the changing doctor-patient relationship emerging in the 1990s, whereas they continued to affirm traditional principles of nonmaleficence and beneficence. PMID- 1910409 TI - Students' evolving attitudes toward family medicine and specialty choices at one medical school. AB - Seventy members of the class that entered Dartmouth Medical School in 1984 responded in 1984 and again in 1988 to statements regarding their attitudes towards family medicine, their general criteria for choosing a specialty, and their concerns about lifestyle; also, the students were asked in 1984 to indicate their interest in a career in family medicine and in 1988 to indicate their long term specialty choices. The students' attitudes towards family medicine were generally positive on entry and became even more positive by their fourth year. Of the 25 students who indicated an initial interest in family medicine, six chose residencies in this field. Because most of the students studied showed strengthening agreement with both (1) the belief that family practitioners are particularly capable of providing comprehensive care and (2) the desire to concentrate on a specialty that would enable them to feel very competent and sure of their work, the authors hypothesize that the students may have feared that their desire for competence and certainty was incompatible with the comprehensiveness of family medicine. PMID- 1910410 TI - Patients', students', and faculty members' perceptions of why patients participated in a physical diagnosis course and what they experienced. PMID- 1910411 TI - Reviewing the Long Island Jewish Medical Center's experience with "mini residencies". PMID- 1910412 TI - A pilot study of the relationship of medical education and moral development. PMID- 1910413 TI - The effect of applicants' gender on the content of a medical school's admission interview. PMID- 1910414 TI - Performances on the Bahrain Licensure Examination by graduates from two types of curricula. PMID- 1910415 TI - The specialty choices and early career development of 1987 and 1991 U.S. medical school graduates. PMID- 1910416 TI - Methodologic aspects of nuclear DNA assessment of gliomas with astrocytic and/or oligodendrocytic differentiation. Correlation of image and flow cytometric studies on paraffin-embedded specimens. AB - A total of 239 samples from paraffin-embedded, formalin-fixed astrocytic and/or oligodendrocytic gliomas from 111 patients were deparaffinized and disaggregated for image cytometric (ICM) and flow cytometric (FCM) DNA assessments. Each measurement technique produced evaluable histograms in about 85% of the samples analyzed. In the 10% that could not be analyzed by FCM, the background counts were too high and the coefficients of variation were too broad for precise evaluation. The failures with ICM were due to a shortage of Feulgen-stained tumor cell nuclei after the deparaffinization and disaggregation procedures. The results obtained were identical in 77% of the samples evaluable by both methods and practically identical (i.e., euploid versus aneuploid) in an additional 18%. The reasons for completely divergent DNA ploidy patterns in 5% of the samples could not be clarified. About 80% of the histopathologically highly malignant gliomas were found to consist of neoplastic cells with an aneuploid or tetraploid nuclear DNA distribution pattern. The results show that cytometric DNA assessments can be reliably performed on paraffin-embedded specimens of gliomas with astrocytic and/or oligodendrocytic differentiation by means of FCM and ICM on deparaffinized and disaggregated specimens. PMID- 1910417 TI - Semiautomation of preparation of fixed paraffin-embedded tissue for DNA analysis. AB - The usual manual preparation of single-cell suspensions from fixed paraffin embedded tissue sections for flow cytometric (FCM) DNA ploidy analysis is a time consuming, labor-intensive technique that requires 70 minutes to deparaffinize and rehydrate 50 microns sections as the initial step. Manual deparaffinization was compared with two semiautomated methods using an automatic slide stainer with either a 70-minute or 35-minute schedule. Samples from 6 normal tissues and 21 tumors (13 diploid and 8 aneuploid) were prepared using all three methods and analyzed by FCM. The mean cell counts in all samples were over 10(6). The DNA indices for the three samples prepared from a given tissue showed no significant differences. Using the 70-minute automation schedule, no aneuploid peaks were lost, and the ratio of G0G1 normal cells to aneuploid tumor cells was maintained. The automation of deparaffinization can thus provide a significant reduction in the labor need to produce single-cell suspensions for FCM; it can be especially helpful when handling large numbers of tumors. At the same time, the automated procedure decreases the exposure to hazardous chemicals and lowers the chance of losing tissue. PMID- 1910418 TI - Qualitative and quantitative analysis of peritoneal fluids from women with gynecologic diseases. Comparison of cytology and flow cytometry for the detection of malignancy in lavage and ascitic fluids. AB - A prospective study was undertaken to compare flow cytometric (FCM) analysis to conventional cytologic evaluation for the detection of malignant cells in peritoneal fluids (peritoneal lavages and ascitic fluids) from women with gynecologic diseases. The 94 peritoneal fluids analyzed came from 63 cancer patients (with epithelial ovarian carcinomas) and 31 control patients (with benign gynecologic diseases). The FCM DNA histograms were generated using propidium iodide as a DNA fluorochrome. Samples for cytologic analysis were stained with the standard May-Grunwald-Giemsa or Papanicolaou stains. Of the 94 samples, 90 were evaluable cytologically while 70 were suitable for FCM analysis. The sensitivities were 55% for FCM DNA analysis and 80% for cytologic analysis. FCM DNA analysis had a 30% false-positive rate; cytologic analysis produced no false-positive results. These results indicate that there is no advantage in employing FCM analysis instead of conventional cytologic evaluation for the detection of malignant cells in peritoneal fluids from gynecologic cases. PMID- 1910419 TI - The role of DNA flow and image cytometry in the evaluation of body cavity fluids. AB - In addition to conventional cytomorphologic study, 50 body cavity fluid specimens (benign and malignant) were analyzed by both flow cytometry (FCM) and image cytometry (ICM) in order to evaluate the potential application of these techniques in the diagnosis of malignancy. While 88% of the fluids were similarly classified by FCM and ICM as being either diploid (66%) or nondiploid (22%), with similar DNA index values, nondiploid peaks were identified by ICM alone in 12% of the fluids. Aneuploid populations were present in 92% of the cytologically positive fluids and in 15% of the cytologically negative fluids. All of the latter fluids came from patients who clinically had tumors involving the respective body cavities. These results show that (1) both FCM and ICM are useful adjuvant techniques in the evaluation of body cavity fluid specimens and (2) ICM is superior to FCM in the identification of small aneuploid subpopulations. The identification of aneuploid populations by either method is highly suggestive of malignancy. PMID- 1910420 TI - Comparison of fine needle aspirates of breast cancers to imprint smears by means of digital cell image analysis. AB - Morphonuclear assessments were performed using the SAMBA 2005 cell image processor on cell nuclei in fine needle aspirates and corresponding imprint smears from 17 not-otherwise-specified (NOS) breast carcinomas to study the influence of cell sampling on the morphonuclear measurements. Fourteen parameters related to densitometric (nuclear DNA content), morphometric (nuclear area) and textural (chromatin organization and distribution) characteristics were computed for each nucleus. The results demonstrated that such morphonuclear features evolved significantly and positively with respect to conventional histopathologic grading. The method of cell sampling significantly influenced the results, but without altering the general conclusions regarding evolution of the morphonuclear features. PMID- 1910422 TI - Fourier analysis of the nuclear and cytoplasmic shapes of living two-cell murine embryos. AB - Living two-cell mouse embryos were flushed out from the oviduct 17, 24 and 36 hours after fertilization in order to obtain cells in the G1S, early G2 and late G2 phases of the second cell cycle. The nuclei of the living cells were stained with Hoechst 33342. The coordinates of the contour shapes of the entire cells (cellular contours) were registered by contour image processing with a TV camera coupled with a computer; the contours of the nuclei were computed by means of a digitizer coupled with the computer. Fourier analysis of the cellular and nuclear contours revealed systematic modifications in the folding of the cells and nuclei in the course of the murine second cell cycle. The progression of cells through the second cell cycle was correlated with an increasing diversification of cellular and nuclear shape, with the diversification being much more pronounced in the nuclear shapes. PMID- 1910421 TI - Flow cytometric DNA content in Kaposi's sarcoma by histologic stage. Comparison with angiosarcoma. AB - Kaposi's sarcoma occurs as a multicentric proliferation of endothelial cells. A lesion may progress through several histologic stages, culminating in a lesion consisting of spindle cells with marked nuclear atypia that may be indistinguishable from angiosarcoma. To assess the relationship between the nuclear DNA content and the stage, 29 paraffin-embedded biopsy specimens from 25 cases of Kaposi's sarcoma were classified according to their histologic stage and flow cytometric DNA ploidy status. The findings were compared with those in 14 angiosarcomas (5 postmastectomy angiosarcomas, 6 other cutaneous angiosarcomas and 3 angiosarcomas of deep tissues). The Kaposi's sarcoma specimens studied included samples with irregular lymphatic-like channels (stage 1), transition to spindle cells (stage 1t2), nodular spindle-cell aggregates (stage 2), scattered atypical spindle cells (stage 2t3) and histologic features indistinguishable from those of angiosarcoma (stage 3). Of the 25 Kaposi's sarcoma specimens of stage 2 or less, 17 had a diploid DNA distribution while an additional 8 had broad diploid G0G1 peaks (peridiploid, with a coefficient of variation greater than 7.5%, present in similar proportions in stages 1, 1t2 and 2). One of three stage 2t3 lesions showed tetraploidy while the single stage 3 specimen (from the leg) was aneuploid, with a DNA index (DI = 1.16) similar to that of four of the five postmastectomy angiosarcomas (DI = 1.14 to 1.20). An additional three angiosarcomas also showed nondiploid distributions (DI = 1.16, 1.98 and 2.13, respectively); the remainder were diploid or peridiploid. These results support previous cytogenetic data suggesting a normal karyotype in Kaposi's sarcoma up to stage 2, with atypia beginning as cells acquire numerical and structural chromosomal aberrations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1910423 TI - Assessment of cell proliferation on porous microcarriers by means of image analysis. AB - Spherical porous microcarriers (PMCs) made from collagen-glycosaminoglycan crosslinked copolymers have exhibited considerable promise as growth surfaces for the proliferation of anchorage-dependent mammalian cell lines and have demonstrated the ability to entrap anchorage-independent cells. However, quantification of cell growth on PMCs has proved difficult. A method of measuring the proliferation of PMCs, based on image analysis, is presented. Using CV1 and CHO cell lines, samples of PMCs were removed from culture at various times, fixed, embedded and sectioned. The 2 microns sections were stained, photographed and digitized in three colors. A computer program was developed to evaluate digitized PMC cross-sections and to classify pixels as conforming to either background, cytoplasmic, matrix or nuclear parameters, based on a set of classification rules determined by statistical analysis. Growth curves were generated by relating the number of pixels occupied by cellular material to the total number of pixels in the PMC cross-section. The PMCs were found to foster cell proliferation, with cell densities approaching 100% occupancy. PMID- 1910424 TI - A systemic lupus erythematosus-derived human hybridoma autoantibody reactive with antigens expressed on ADP-activated platelets. AB - Hematological complications seen in systemic lupus erythematosus (SLE) patients may be caused by the binding of specific autoantibodies to platelets, but the epitopes on platelets responsible for antibody binding and the mechanisms by which autoantibodies induce hemostatic abnormalities in SLE patients remain unknown. We have previously demonstrated that polyspecific platelet-binding antibodies can be derived from SLE patients. In the present study, we have characterized an SLE-derived polyspecific hybridoma antibody, 9604, which was previously shown to be strongly cytotoxic to platelets in vitro and to have weak lupus anticoagulant activity. We demonstrated that this antibody does not bind to fixed intact platelets in an enzyme-linked immunoassay (ELISA), but does react with lysed, washed or ADP-activated platelets. By Western blotting analysis, antibody 9604 was unique among other platelet-binding autoantibodies in that it reacted mainly with polypeptides of approximately 200,000 and 32,000 molecular weight (MW) in platelets. In blots of endothelial cell proteins, 9604 reacted with a band of approximately 200,000 MW, but no 32,000 MW reactive band was observed. Based on these findings, we postulate that antibody 9604 may bind to a protein or proteins of 32,000 MW exposed on the platelet surface during activation. To our knowledge, this is the first demonstration of a human hybridoma monoclonal antibody derived from an SLE patient which distinguishes between activated and resting platelets. Further characterization of the proteins recognized by this autoantibody may provide insight into the mechanisms responsible for the production and pathogenesis of anti-platelet autoantibodies in patients with SLE. PMID- 1910425 TI - A role for DNA in anti-DNA antibodies binding to endothelial cells. AB - Vascular injury and microvascular thrombosis are prominent features of systemic lupus erythematosus, as are circulating DNA-binding antibodies (DNAb). Experimental glomerulonephritis can be induced by anti-endothelial cell antibodies, and polyreactive DNAb might be pathogenetic by binding to endothelial cells, perhaps influencing their non-thrombogenic nature. To test this hypothesis, eight monoclonal antibodies (mAb) that bind to DNA derived from (NZB x NZW)F1 or MRL/Mp-lpr/lpr mice, were tested for their ability to bind to human umbilical vein endothelial cells (HUVEC). Binding was assessed using flow cytometry, fluorescence microscopy and cellular ELISA. Three of the eight mAb, at concentrations employed in this study, bound to HUVEC and dermal fibroblasts. Of these three mAb, one bound also to platelets. Two of the three demonstrated strong binding to (1) freshly isolated, collagenase-digested HUVEC, (2) 2nd passage HUVEC in suspension after trypsinization and, (3) 2nd passage HUVEC growing on plastic plates. To determine whether DNA itself acted as a ligand in this binding, prior treatment with DNAase was studied. Treatment of the endothelial cells with DNAase had no effect on the binding of one mAb, but DNAase treatment of this monoclonal itself resulted in a 60% reduction in binding to HUVEC, suggesting that the binding might be mediated through DNA in the form of a DNA/anti-DNA immune complex. In contrast, DNAase digestion of the endothelial cells caused a 40% reduction in the binding of the other two monoclonal antibodies. Furthermore, one of the two mAb bound 30% more to HUVEC after themselves being subjected to DNAase treatment. These two monoclonals may therefore be binding directly to HUVEC, possibly to DNA associated with the membrane. Prior DNAase digestion of dermal fibroblasts had a more profound effect on the binding of all three autoantibodies compared to HUVEC after similar treatment. Therefore, DNA can bind independently to either antibody or cell, thus supporting build up of complexes and capture of preformed complexes. Functionally, the binding of mAb to HUVEC did not influence thrombin-induced prostacyclin synthesis, in contrast to a control monoclonal anti-endothelial cell antibody EN4, which did. PMID- 1910426 TI - Induction of oral tolerance to S-antigen induced experimental autoimmune uveitis by a uveitogenic 20mer peptide. AB - Experimental autoimmune uveitis (EAU) in Lewis rats is a T-cell dependent disease, which is induced by immunization with retinal S-Antigen (S-Ag) or its unveitogenic peptides. We have recently reported that the oral administration of S-Ag prior to the uveitogenic challenge results in suppression of the disease and of the cellular responses. We examined the effect of oral administration of a recently described uveitogenic peptide (Peptide 35) on the development of EAU induced with the whole protein. The severity of inflammation and retinal destruction, as well as the cellular proliferative responses, were suppressed compared to controls fed with Keyhole Limpet Hemocyanin (KLH). In addition, the levels of antigen-specific antibody isotypes in the serum of gavaged rats were determined. Although (IgA) levels were reduced in rats gavaged with S-Ag or the uveitogenic peptide, IgM and IgG levels were unaltered. Thus, the oral administration of Peptide 35 approaches the state of unresponsiveness seen in S Ag feeding. In addition, the unresponsiveness can be demonstrated on both the cellular and humoral level. PMID- 1910427 TI - Immunogenetic heterogeneity in type I (insulin-dependent) diabetes among the Tunisian population. HLA-DR antigens and organ-specific autoantibodies (family study). AB - The frequency of HLA-DR antigens, as well as the prevalence of islet cell insulin autoantibodies and other autoimmunity disorders, were investigated in Tunisian patients with insulin-dependent diabetes mellitus (IDDM) and were compared with family members (sibs) and healthy control subjects. Cytoplasmic islet cell autoantibodies (ICA) were found in 79 of 175 (45.1%) patients with IDDM, in 23 of 126 (18.25%) unaffected first degree relatives of type I diabetes patients and in only two of 146 (1.3%) control subjects. In 79 ICA positive patients with IDDM, 46.8% presented other evidence of autoimmunity by testing for specific autoantibodies. Insulin autoantibodies were found in 86.9% of healthy ICA positive sibs. A good correlation between HLA-DR3/DR4 heterozygous phenotypes and the presence of ICA in patients with IDDM and their unaffected sibs was observed in the Tunisian population. In fact, this heterozygous phenotype is found in 63.3% of ICA-positive diabetic patients and in 44.4% of ICA-positive unaffected sibs, whereas, HLA-DR3/DR4 antigens were noted in only 22.9% of ICA-negative diabetic patients and in no ICA-negative unaffected sibs. In these studies, we also summarized the distribution of HLA-DR antigens in patients with IDDM who presented autoimmune disorders other than ICA. PMID- 1910428 TI - A comparison of the effects of hyperbaric oxygen culture on survival of murine and canine thyroid gland grafts. AB - Canine thyroid tissue (CTy) was subjected to hyperbaric oxygen culture (HOC) under conditions that affect immunoalteration in murine thyroid tissue (MTy). Survival of autografts and allografts implanted under the kidney capsule was determined after 21 days by 125I uptake and histology. Unlike MTy, autograft CTy subjected to normothermic HOC (95% O2, 5% CO2; 1.76 kg/cm2) for 48 h did not survive (0/8) whereas decrease of culture duration to 24 h resulted in autograft CTy survival (3/3). Under hypothermia (5 degrees C), HOC could be extended to 7 days with autograft CTy survival (3/3 after 4 days and 3/3 after 7 days). Allograft CTy after 24 h of normothermic HOC and 7 days of hypothermic HOC was rejected. Indicators of oxygen free radical injury were determined:catalase activity was comparable in MTy and CTy (means 14.82 and 6.3-10.8 mm/mg protein, respectively) but superoxide dismutase activity was low in CTy (means 0.01-0.29 and 4.75 U/mg protein, respectively). Malondialdehyde content after 48 h of normothermic HOC was higher in CTy than in MTy (means 2215 and 1275 nmol/g, respectively). The results show that CTy is injured by HOC under conditions tolerated by MTy, and that this difference is related to the greater sensitivity of CTy to oxygen free radical injury. PMID- 1910429 TI - Arterial steal: an unusual cause for hepatic hypoperfusion after liver transplantation. AB - Case reports of two patients with an unusual cause for a rapid increase in transaminases following liver transplantation are described. In the postoperative course, angiography revealed an arterial hypoperfusion of the liver due to a steal phenomenon with blood shunting from the hepatic to the splenic artery. In one case, the underlying pathophysiology was a pre-existing filiform stenosis of the celiac trunk with insufficient recruitment of arterial blood from the superior mesenteric artery via the pancreatic arcade. Adequate liver perfusion was restored by simple ligation of the common hepatic artery. In the other case, angiography showed an arteriovenous fistula formation of the splenic vessels and minimal blood flow through the hepatic vessels. This was successfully corrected by angiographic embolization of the splenic artery with metal coils. After therapeutic intervention, both patients rapidly recovered with excellent liver function. PMID- 1910430 TI - Cyclosporin A blood levels during use of cyclosporin as oral solution or in capsules: comparison of pharmacokinetic parameters. AB - Recently cyclosporin A (CsA) capsules have been introduced to meet a number of disadvantages associated with the use of the oral solution. We compared the pharmacokinetics of the oral solution and the capsules in a group of nine renal transplant patients during the first 3 weeks after transplantation. After a morning dose of CsA, whole blood concentrations were measured at regular intervals for 12 h. Subsequently, a cross-over was made to the alternative form of administration, and 3 or 4 days later a second pharmacokinetic profile was obtained. Comparison of the trough level, the maximum concentration, the time to reach the maximal concentration and the area under the blood concentration curve, showed no significant differences. Our findings thus suggest a similar bioavailability of CsA administered as oral solution or in capsules in the early post-transplant period. PMID- 1910431 TI - Graft-versus-host disease in solid organ transplantation. AB - Graft-versus-host disease is well recognized in bone marrow transplantation, but has only recently been described in solid organ transplantation. Two such cases in liver graft recipients, proven by the demonstration of donor type HLA antigens in the peripheral blood and marrow on tissue typing, are described in this paper. The literature on this subject is reviewed and the treatment discussed. It is postulated that there is an order of risk of development of graft-versus-host disease depending on the amount of viable lymphoid tissue included with the transplanted organ as follows: small bowel greater than heart-lung greater than liver greater than kidney greater than heart. It seems likely that this condition has been substantially underdiagnosed in the past and that greater awareness of the possibility of graft-versus-host disease in solid organ recipients will lead to the recognition of further cases and allow appropriate treatment to be promptly instituted. PMID- 1910432 TI - Evaluation of the formula clearance as a measure of the glomerular filtration rate in cyclosporin-treated children following renal transplantation. AB - Since the introduction of the nephrotoxic drug, cyclosporin, as the main immunosuppressive agent following organ transplantation, the need for an accurate method to determine the glomerular filtration rate (GFR) has arisen. In the present study the clearance of inulin has been compared to the clearance of creatinine estimated by short-term urine sampling or by the formula clearance in 29 children following renal transplantation. The children, 0.4-15.4 years of age at transplantation, were examined within 5 months following transplantation, and thereafter yearly. During the first 2 years after transplantation there was poor agreement between inulin clearance and formula clearance, while 3-4 years after transplantation there was good correlation between the two methods. However, the formula clearance generally overestimated GFR and the overestimation increased with decreasing renal function. In spite of the good correlations between the two methods after the first years following transplantation, the formula clearance in individual patients does not follow the inulin clearance changes very closely. In conclusion, formula clearance was found to be an inaccurate method of following GFR, especially during the first 2 years after transplantation. This might be caused by changes in habitus as well as an increased creatinine secretion caused by cyclosporin. PMID- 1910433 TI - The relevance of more sensitive ancillary crossmatch techniques in predicting early cadaver renal graft outcome. AB - The predictive value of varying levels of antibody activity, its class and antigen specificity in sera of 81 recipients of cadaver renal allografts was evaluated. Recipients for transplantation were selected on the basis of a negative dye uptake T-cell crossmatch, after which the more sensitive 51Cr release technique was employed in a blind study using unseparated donor target cells. Recipient sera with peak panel reactivity and current samples were evaluated before and after reduction with dithiothreitol to destroy the IgM subclass. Double absorption with pooled platelets allowed antibodies against HLA class I antigens to be distinguished from those against HLA class II/non-HLA antigens. Optimal levels of cytotoxicity were established, giving a sensitivity of 73%. Data were assessed in terms of positive predictive value, and showed that conventional T-cell crossmatching is adequate for the primary transplant group, but more sensitive ancillary tests are indicated for regrafts. In this category of patients, IgG antibodies, whether against HLA class I antigens or HLA class II/non-HLA antigens, were highly predictive of early graft loss (positive predictive value 50%-100%). Using this protocol for patient selection, 1-month graft survival would have improved from 73% to 96%. PMID- 1910434 TI - 31P-NMR study of cardiac preservation: St. Thomas' Hospital cardioplegic solution versus UW preservation solution. AB - Ex vivo cardiac preservation was evaluated by measuring the catabolism of high energy phosphate (ATP and creatine phosphate, CrP) using 31P-NMR spectroscopy. After cardioplegic arrest St. Thomas' Hospital cardioplegic solution (group A), and University of Wisconsin (UW) preservation solution (group B) were tested. The hearts were mounted in the 4.7 T horizontal bore magnet of the NMR spectrometer and were continuously perfused with the test solution under 25 cm H2O pressure for 6 h at 10 degrees C. Peak heights of the beta-phosphate of ATP and CrP were measured and expressed as percentages of the initial value. For both group A and group B. ATP declined less rapidly during preservation than CrP. In group A, ATP remained constant for 60 min while CrP decreased from the onset of preservation. After 6 h of preservation 28.3% of ATP and 24.5% of CrP remained (group A). On the other hand, in group B, levels of both ATP and CrP remained much more stable: CrP did not decrease during the first 3 h of preservation, while ATP started to decrease after 5 h. At the end of preservation 76.1% of ATP and 71.5% of CrP were still present. We conclude that UW solution is superior to St. Thomas' Hospital solution for the preservation of high-energy phosphates during 6 h cardiac preservation with continuous hypothermic low-flow perfusion. PMID- 1910435 TI - Donor-recipient age difference--an independent risk factor in cyclosporin-treated renal transplant recipients. AB - Whilst HLA matching is routine in renal transplantation the possible benefits of matching donor to recipient age have not been previously explored. The simultaneous effect on graft survival of donor and recipient age was therefore investigated for 274 consecutive first cadaver transplant recipients treated by cyclosporin immunosuppression in two centres. The overall graft survival was 77%, and was not significantly different between the two centres. Individually there was no significant effect of donor or recipient age but taken together, the difference in age significantly affected graft survival (P less than 0.01) regardless of the mode of failure. The 1-year graft survival for all failures was 66.2% when the donor was 5 or more years older. 84.5% when the donor was 5 or more years younger and 71.7% when the donor was within 5 years of the recipient's age. Multivariate analysis, taking into account other variables (HLA matching, dialysis time and type, donor/recipient sex, local/imported kidneys, sensitivity, operation time, total ischaemic time, pre-operative transfusions) indicated that age difference was the single most important variable (P less than 0.01). The only other important covariate risk factor in improving graft survival was HLA-DR matching (P less than 0.05). Donor-recipient age difference is a potentially important recipient selection criterion in cyclosporin-treated renal transplant patients. PMID- 1910436 TI - Impact of long-term immunosuppression with cyclosporin A on serum lipids in stable renal transplant recipients. AB - To determine the impact of long-term immunosuppression on serum lipids in stable renal graft recipients we measured serum lipids and apolipoprotein B concentrations in 20 patients receiving therapy with cyclosporin (CsA) and low dose prednisolone (CsA/P) and in 18 patients on therapy with azathioprine and maintenance steroids (Aza/P). The patients were matched for age, body mass index, primary renal disease and dose of prednisolone, but not for the duration in transplantation and serum creatinine concentration. Triglyceride concentrations were significantly higher in the CsA/P group than in Aza/P-treated patients: 2.62 +/- 0.35 vs 1.62 +/- 0.23 mmol/l (P less than 0.05). Similarly, total cholesterol (C) levels were significantly more elevated in the CsA/P recipients than in the other group: 7.44 +/- 0.32 vs 5.84 +/- 0.25 (P less than 0.02). CsA/P patients had higher serum levels of LDL-C (4.79 +/- 0.20 vs 3.43 +/- 0.19 mmol/l (P less than 0.001) and apolipoprotein B concentrations (191 +/- 13 vs 128 +/- 9 mg/dl: P less than 0.001). CsA/P and Aza/P recipients had similar concentrations of HDL-C (1.73 +/- 0.13 vs 1.52 +/- 0.09 mmol/l: NS). We conclude that in stable renal graft recipients with good transplant function long-term immunosuppression with CsA/P is associated with a more atherogenic lipid status than therapy with Aza/P. PMID- 1910437 TI - Treatment of pure red-cell aplasia following major ABO-mismatched T-cell-depleted bone marrow transplantation. Two case reports with successful response to plasmapheresis. AB - Major ABO-mismatched bone marrow transplantation (BMT) may be accompanied by red cell haemolysis, but pure red-cell aplasia following BMT is a rare complication. Two cases of transient pure red-cell aplasia following T-lymphocyte-depleted BMT for a period of greater than 20 weeks are described, both of which responded to one cycle of plasmapheresis. The prompt response of the two patients described with red-cell aplasia with no evidence of haemolysis suggests that plasmapheresis may be considered in such clinical situations as a first treatment of choice before attempting more complex modes of therapy. PMID- 1910438 TI - Nonleast-squares jackknife regression in drug design. AB - Nonleast-squares jackknife regression was applied to model a quantitative structure-activity relationship (QSAR) analysis of butyrophenones. Dependent physicochemical and dependent psychopharmacological parameters were correlated, and the robustness of the model was confirmed by resampling. PMID- 1910439 TI - Enhanced skin permeation of papaverine by a medium chain glyceride. AB - The mode and mechanism of action of Sefsol-318, a medium chain glyceride and a potent percutaneous absorption enhancer, on the in vitro permeation of papaverine hydrochloride through hairless rat skin were investigated and compared with those of laurocapram (Azone). The total amount of the drug delivered through excised skin over 28 h from aqueous solutions of the drug in which 5% S-318 or Azone was suspended was about 820 or 420 times higher, respectively, than from the solution alone. Experiments using liposomes as models, indicated that both the enhancers markedly increased the fluidity of lipid membranes. Skin conductance measurements in hairless rats indicated that they both also increased in vivo skin moisturizing and water holding capacity. These results suggest that the mechanism of action of Sefsol-318 and Azone in enhancing skin permeation are similar. But following in vitro pretreatment of the excised skin with 5% Sefsol-318 and aqueous emulsion for 2 h, skin permeation of papaverine hydrochloride through the pretreated skin was much lower than through non-treated skin in the presence of Sefsol-318. In contrast, the enhancing effect of Azone on the pretreated skin was similar to that of Azone on the in vitro non-treated skin. We found that, unlike Azone, Sefsol-318 disappeared from skin completely one day after 24 h-in vivo pretreatment of skin with aqueous gels containing each agent. In agreement, drug permeation through skin excised one day after the in vivo pretreatment with Sefsol-318 was almost the same as in non-pretreated controls without Sefsol-318. This difference in the mode of action of Sefsol-318 and Azone may arise from the difference in the residence times of these enhancers in skin. PMID- 1910440 TI - Thermo-responsive hydrogels based on acryloyl-L-proline methyl ester and their use as long-acting testosterone delivery systems. AB - New thermo-responsive hydrogels were synthesized by copolymerizing acryloyl-L proline methyl ester (A-ProOMe) with minor amounts of 2-hydroxypropyl methacrylate (HPMA) or polyethylene glycol 600 dimethacrylate (14G), using gamma rays from a 60Co source. In water, extensive swelling of the hydrogels occurred at 10 degrees C, but there was marked deswelling as the temperature was raised to 37 degrees C. The poly(A-ProOMe-co-HPMA) hydrogel was characterized by an initial rapid shrinkage at the surface in the deswollen state; this shrinkage arose because of the formation of a rigid membrane barrier devoid of micropores. The system is therefore 'surface regulated'. In contrast, no such a barrier formed in the deswollen poly(A-ProOMe-co-14G) hydrogel. The whole matrix shrunk without the disappearance of micropores, and it is therefore a 'matrix pumping' system. Testosterone was incorporated into both these types of hydrogels, and the drug loaded hydrogels were implanted subcutaneously into the backs of castrated rats. The daily dose of testosterone released in vivo from the poly(A-ProOMe-co-HPMA) hydrogel was constant at approximately 30 micrograms/day throughout an experimental period of 54 weeks. In contrast, drug release from the poly(A-ProOME co-14G) hydrogel reached a maximum after one week and then decreased linearly with time down to the 7th week, when it was undetectable. These conclusions were supported by the changes in weight of the ventral prostates and right-side seminal vesicles of the rats, which were restored to normal when delivery of the testosterone was sustained. PMID- 1910441 TI - New approaches to drug design and delivery based on drug-membrane interactions. AB - In this review, the complex physical and chemical interactions of drugs with model and biological membranes under normal and pathological conditions are examined at the molecular level. The results of our own published and unpublished structural studies are discussed and correlated with kinetic binding studies to assess the potential role of nonspecific drug interaction with the membrane bilayer in the overall receptor binding mechanism for membrane-bound receptors in heart and brain. PMID- 1910442 TI - 5-HT3 receptor antagonists. PMID- 1910443 TI - A theoretical model for the histamine H2-receptor. AB - We describe an electronic and conformational study of histamine H2-receptor ligands of the imidazole series, in which the possibilities of configurational isomerism (the thiourea group) and N3H and N1H tautomerism (imidazole ring) were considered. The results suggest that the conformational flexibility of the molecules and the properties of the imidazole ring are of special importance in the display of H2-receptor activity. A theoretical model of histamine H2-receptor interactions is proposed on the basis of these and other results. A very important characteristic of our model is its ability to explain H2-receptor activation by compounds which differ structurally, and to explain antagonism at the same receptor. The stereospecificity of rigid analogues of cimetidine and tiotidine, and the importance of chain length in flexible histamine H2 antagonists are also accounted for. PMID- 1910444 TI - Linear free energy-related and quantitative structure-activity relationships of inhibitors of thymidylate synthetase. AB - Thirteen previously described 5-(p-substituted-phenyl)-2'-deoxyuridines were synthesized, and the NMR and IR spectra of their 2,4-dioxopyrimidine (2,4-DP) rings were correlated against linear free energy-related and extrathermodynamic parameters. We conclude that the 5-phenyl ring is probably oriented over the plane of the 2,4-DP ring (sandwich structure, Figure 6). The main component of the spectroscopic data is largely determined by the stereoelectronic nature of the para-groups in the 5-phenyl ring, while a second component is largely determined by apolar forces. The inhibitory activity of the compounds against thymidylate synthetase is enhanced by the presence of apolar groups with a positive inductive effect, provided these groups do not extend the plane of the 2,4-DP ring. PMID- 1910445 TI - Structural and microbiological evaluation of a degradable sustained-release device for use in periodontal therapy. AB - Degradable protein matrices containing chlorhexidine were tested as intra-pocket drug delivery systems in the treatment of periodontal diseases. The properties of the device were mainly dependent upon the degree of cross linking in the matrix, which could be varied according to the preparative conditions. The degree of cross linking was determined by amino acid analysis based on the amount of free lysine in the protein. The release of chlorhexidine and of the plasticizer used in the preparation of the matrix were determined. The release of chlorhexidine from the matrix was prolonged for a period of 300 hours, and the release of plasticizer ceased after four hours. Limited clinical trials suggest that one of the degradable devices--that containing the highest amount of cross-linking- causes a significant reduction in the amount of perio-pathogenic bacteria following its insertion into the periodontal pockets of patients with periodontal disease. PMID- 1910446 TI - Mitogenic properties of major extracellular proteins. AB - The major plasma and extracellular matrix proteins are multifunctional molecules. Some, such as fibrinogen or C3, have one domain that binds adhesion receptors and another that specifically binds and activates a separate, mitogenic receptor. In this review, Jean-Pierre Levesque, Antoinette Hatzfeld and Jacques Hatzfeld describe adhesion and mitogenic receptors that bind to distinct domains of the same extracellular matrix protein and discuss the possibility of common ancestral genes for cell adhesion molecules, extracellular matrix proteins, integrins, immunoglobulins, growth factors and their receptors. PMID- 1910447 TI - Recognition of self within self: specific lymphocyte positioning and the extracellular matrix. AB - In this article, Maria de Sousa and colleagues address the importance of interactions between lymphocytes and extracellular matrix components to lymphocyte migration and positioning, emphasizing the role of the basement membrane and the complex stromal matrix of the lymphoid organs. They conclude that such interactions are of great importance, both in the physiological functioning of the immune system and in organ transplantation. PMID- 1910448 TI - What is the basis for HLA-DQ associations with autoimmune disease? AB - The finding that diseases such as type I diabetes, coeliac disease and multiple sclerosis are HLA-DQ associated is not easily explained by a simple hypothesis of DQ-restricted, autoreactive T cells, considering the generally marginal role of DQ in restricting responses. Consequently, there have been various attempts to find a differential role for DQ, from presentation of special antigens to preferential stimulation of suppressor cells. Here, Daniel Altmann and colleagues critically assess these proposals and put forward the alternative hypothesis that the effect of DQ on disease susceptibility may result from a special role in shaping the T-cell receptor repertoire. PMID- 1910449 TI - The Mycoplasma arthritidis T-cell mitogen, MAM: a model superantigen. AB - The superantigens are receiving a great deal of attention as a new group of potent immunomodulatory molecules. They are produced by diverse microbial agents including staphylococci, streptococci and mycoplasmas and are also encoded by murine tumor viruses (the Mls antigens). Superantigens activate T cells by a unique pathway which can lead to modification of the T-cell repertoire and induction of autoimmunity. Here, Barry Cole and Curtis Atkin review their observations on the Mycoplasma arthritidis superantigen, MAM, and discuss how MAM might contribute to the acute and chronic inflammatory disease mediated by this organism. PMID- 1910450 TI - Experiments of nature in the development of modern immunology. PMID- 1910451 TI - Purification and properties of branched-chain alpha-keto acid dehydrogenase kinase from bovine kidney. AB - Branched-chain alpha-keto acid dehydrogenase (BCKDH) kinase was purified 5000 fold to apparent homogeneity from extracts of bovine kidney mitochondria. The kinase co-purified with the BCKDH complex. About 70% of the kinase was released by treatment of the complex with 1.5 M NaCl and 0.1% 2-mercaptoethanol at pH 7.4, followed by chromatography on Sephacryl S-400. The uncomplexed kinase was purified further by chromatography on Q Sepharose and Superose 12. The purified kinase is a monomer of apparent Mr approximately 43,000. BCKDH kinase exhibited little activity, if any, toward pyruvate dehydrogenase. PMID- 1910453 TI - Identification of a novel tatiopterin derivative in Methanogenium tationis. AB - Recently, a novel pterin has been isolated from Methanogenium tationis. This pterin derivative, which was called tatiopterin, was characterized as a methanopterin-like structure with an additional aspartyl and glutamyl group in the side chain and with a 7-proton instead of a 7-methyl group in the pterin moiety. The sequence of the aspartyl and glutamyl group remained unsolved. In this study, a novel pterin was purified from Mg.tationis and analyzed by 600 MHz 1H-NMR spectroscopy and fast atom bombardment-mass spectroscopy. This pterin was found to be an aspartyl derivative of methanopterin with a 7-proton in the pterin part of the molecule. No glutamyl group could be detected. Apparently, Mg.tationis is able to synthesize two types of tatiopterin derivatives. For these cofactors the trivial names 'tatiopterin-0' (lacking a glutamyl group) and 'tatiopterin-I' (containing one glutamyl group) are introduced here. PMID- 1910452 TI - Synergistic influence of epidermal growth factor, insulin and transferrin on human fetal kidney in culture. AB - In human fetal kidneys (15-21 weeks of gestation) maintained in serum-free organ culture, protein synthesis remained relatively constant, but DNA synthesis decreased dramatically after 2 days. The addition of transferrin alone had no influence, but insulin and epidermal growth factor (EGF) both significantly stimulated DNA and protein synthesis. When supplemented in combination, transferrin strongly potentiated the insulin effect and after 5 days of culture DNA synthesis was practically restored to values observed in control uncultured renal explants (day 0). When EGF, a potent mitogen, was added as a third factor, the stimulating effectiveness of the (insulin plus transferrin) combination was significantly reduced. However, EGF had no such inhibiting influence on protein synthesis. Differentiation of brush border membranes, as evaluated by hydrolase activities, was not importantly induced nor retarded by any of the three factors supplemented either alone or in combination. The present results indicate that the individual effects of the three factors are not additive, but suggest that they rather act synergistically through a complex mechanism of receptor cross talk. In our laboratory, there is convincing indication that the response of fetal organs varies according to age, proliferative state of tissues as well as stage of differentiation. PMID- 1910454 TI - Flavoproteins with a covalent histidyl(N3)-8 alpha-riboflavin linkage. PMID- 1910455 TI - Iron-catalyzed reactions may be responsible for the biochemical and biological effects of asbestos. AB - The most carcinogenic forms of asbestos contain iron to levels as high as 36% by weight and catalyze many of the same biochemical reactions that freshly prepared solutions of iron do, i.e. oxygen consumption, generation of reactive oxygen species, lipid peroxidation and DNA damage. The participation of iron from asbestos in these reactions has been demonstrated using the iron chelator desferrioxamine B which inhibits iron-catalyzed reactions. Iron appears to be redox active on the asbestos fiber, but chelation and subsequent iron mobilization from asbestos by a variety of chelators, e.g. citrate, EDTA or nitrilotriacetate, makes the iron more redox active resulting in greater oxygen consumption and production of oxygen radicals in the presence of reducing agents. Iron also appears to be important for some of the asbestos-dependent biological effects on tissues or cells in culture, such as phagocytosis, cytotoxicity, lipid peroxidation and DNA damage. Therefore, redox cycling of iron to generate oxygen radicals at the surface of the fiber and/or in solution, as mobilized, low molecular weight chelates, may be very important in eliciting some of the biological effects of asbestos in vivo. PMID- 1910456 TI - Biochemistry of methionine sulfoxide residues in proteins. AB - The oxidation of methionine to methionine sulfoxide constitutes one of the many post-translational modifications that proteins undergo. This non-enzymatic reaction has been shown to occur both in vivo and in vitro, and has been associated with the loss of biological activity in a wide variety of proteins and peptides. The presence of methionine sulfoxide residues in proteins is implicated in a variety of pathological conditions. An enzyme that is present in all organisms tested specifically catalyzes the reduction of the methionine sulfoxide residues in proteins. The physiological reductant for this enzyme appears to be thioredoxin. PMID- 1910457 TI - The complete primary structure of the marine Carnivora, galapagoes fur seal (Arctocephalus galapagoensis, Otariidae) hemoglobins. AB - The complete primary structure of the two hemoglobin components of the fur seal (Arctocephalus galapagoensis) is presented. The two components (HbI and HbII) occur in nearly equal amounts and have identical beta-chains; whereas the two alpha-chains (alpha I/alpha II) differ by six exchanges Ile/Val, Met/Thr, Ser/Ala, Pro/His, Lys/Gly, and Thr/Ala at positions 10, 34, 35, 50, 78, and 131, respectively. The components were isolated by DEAE-Sephacel chromatography and were separated into the globin chains by RP-HPLC on a column of Nucleocil-C4. The sequences have been determined by Edman degradation in liquid- and gas-phase sequencer, using the native chains and tryptic peptides. The sequences compared with those of other Carnivora species and an adult human globin chains. An identical beta-chain is found in fur seal and walrus, whereas larger differences were found between alpha I and alpha II compared to beta-chains. PMID- 1910458 TI - A CHARMM analysis of the conformations of the metastasis-inhibiting laminin pentapeptide. AB - The metastatic invasion of basement membrane by tumor cells involves the binding of tumor cells to laminin. Laminin, a glycoprotein, is a major component of basement membrane. Both tumor and normal cells express a high-affinity receptor for laminin; however, the expression is more pronounced with tumor cells. The pentapeptide, Tyr-Ile-Gly-Ser-Arg, (YIGSR), an amino acid sequence from the B1 chain of laminin, was found to compete with laminin for binding to the laminin receptor. The binding of tumor cells to laminin can be inhibited competitively by YIGSR and, in mice, this has been shown to be translated into a reduction in metastasis. Reports of structural modifications of YIGSR leading to molecules with enhanced activity led us to attempt to learn more about the secondary structure of YIGSR. Through the use of CHARMM, a molecular mechanics program, we were able to discover a conformation of N-acetyl-YIGSR-NHCH3 that is stable over a wide range of dielectric constants. In this conformation the arginine side chain acts to hold Tyr, Ile, and Gly in a partial right-handed alpha helix. We speculate that this partial alpha helical structure is necessary for binding to the lamin receptor and thereby its antimetastatic activity. PMID- 1910459 TI - Investigation of a physical basis for conformational similarity in proteins. AB - Amino acid residues in a globular protein fold against one another into a compact structure. We have sought common physical factors within similarly folded backbone structures in such proteins which might influence the folding and which could be used in predicting the backbone structure. The physical factors examined are the 10 orthogonal ones identified by Kidera et al. (1985a). Comparison of the smoothed physical factor profiles between sequences, which have similar backbone structures, shows that there is good agreement among the profiles of helical stretches, but not for other backbone structures that have been examined. This is ascribed to the fact that helical structures involve local interactions, which then require similar physical profiles to form, but that other structures are not so strongly locally determined in the native structure. PMID- 1910460 TI - Protection and enhancement of ribulose 1,5 bisphosphate carboxylase activity by exogenous proteins. AB - When assayed in vitro, the activity of the photosynthetic enzyme ribulose 1,5 bisphosphate carboxylase oxygenase is both enhanced and protected from spontaneous decay by exogenous proteins such as hemoglobin, serum albumin, and aldolase. Other proteins and amino acids tested are either ineffective (lysozyme, ferritin, lysine, and cysteine) or afford only partial protection (catalase, glycine, and phenylalanine). Protective proteins do not bind to, or exchange disulfides with, ribulose 1.5 bisphosphate carboxylase/oxygenase. Since their effect can be mimicked by reductively treated detergents such as Triton X-100, it appears that proteins protect from decay by quenching the spontaneous oxidative degradation and inhibiting surface adsorption which could lead to enzyme unfolding. Release of adsorbed molecules from the container surface is likely to be the cause of carboxylase activity enhancement. PMID- 1910461 TI - Structural stability of lipase from wheat germ in alkaline pH. AB - The present investigation shows the effect of alkaline pH on the structure function relationship of lipase from wheat germ. There is a 70% decrease in lipase activity at pH 10.0, which decreases to 93% at pH 12.0 as compared to neutral pH activity (Rajendran et al. 1990). This change is shown to be as a result of loss of alpha-helical structure with a concomitant increase in aperiodic structure. The results with fluorescence spectra and tyrosyl ionization indicate gradual exposure of aromatic side chains of tyrosine and tryptophan to the bulk solvent along with the structural changes. The enzyme is in an extended form at alkaline pH with a volume change of - 1300 ml mol as also indicated by increase in reduced viscosity to 12.5 ml g and significant decrease in sedimentation coefficient. The kinetics of the reaction points to a cooperative pseudo first-order reaction as determined by stopped-flow kinetic analysis in the ultraviolet region. The inactivation mechanism appears to follow a two-step mechanism of a fast and a slow reaction. PMID- 1910462 TI - Calorimetric and spectroscopic examination of the solution phase structures of prekallikrein binding domain peptides of high molecular weight kininogen. AB - Unique sequence-binding sites are exposed on the surface of high molecular weight kininogen which complex prekallikrein or factor XI with high affinity and specificity. A sequence comprising 31 residues of the mature kininogen molecule (Asp565-Lys595) retains full binding activity for prekallikrein (KD = 20 nM) and assumes a complex folded structure in solution which is stabilized by long-range interactions between N- and C-terminal residues. The sequence Trp569-Lys595 (27 residues) shows only 28% of this binding affinity and lacks the key structural features required for protein recognition (Scarsdale, J. N., and Harris, R. B., J. Prot. Chem. 9, 647-659, 1990). We were thus able to predict that N- or C terminal truncations of the binding-site sequence would disrupt the conformational integrity required for binding. Two new peptides of 20- and 22- residues have now been synthesized and their solution phase structures examined. These peptides are N- and C-terminal truncations, respectively, of the 27-residue sequence and correspond to the sequences Asp576-Lys595 and Trp569-Asp590 of high molecular weight kininogen. The results of fluorescence emission and circular dichroism (CD) spectroscopies in the range 25-90 degrees C and from differential scanning calorimetry (DSC) all substantiate the idea that the C-terminal truncation peptide binds prekallikrein 35-fold poorer than the 31-residue peptide because it is relatively unordered and possesses a less stable structure. Surprisingly, the N-terminal truncation peptide (20-mer) shows structural stability even at elevated temperatures and, like the 31-residue peptide, undergoes cold-induced denaturation observable in the DSC. 2D-NMR analysis of the 20-residue peptide revealed two distinct structures; one conformer possesses a more compact, folded structure than the other. However, the predicted structures assumed by either conformer are very different from those of either the 31- or 27 residue peptides. Hence, the binding affinity of the 20-residue peptide is 60 fold poorer than that for the 31-residue peptide because it assumes a nonproductive binding conformation(s). PMID- 1910463 TI - Insulin analogues with modifications in the beta-turn of the B-chain. AB - The beta-turn formed by the amino acid residues 20-23 of the B-chain of insulin has been implicated as an important structural feature of the molecule. In other biologically active peptides, stabilization of beta-turns has resulted in increases in activity. We have synthesized three insulin analogues containing modifications which would be expected to increase the stability of the beta-turn. In two analogues, we have substituted alpha-aminoisobutyric acid (Aib) for the Glu residue normally present in position B21 or for the Arg residue normally present in position B22; in a third compound, we have replaced the Glu residue with its D-isomer. Biological evaluation of these compounds showed that [B21 Aib]insulin displays a potency ca. one-fourth that of natural insulin, while [B22 Aib]insulin is less than 10% as potent. In contrast, [B21 D-Glu]insulin is equipotent with natural insulin. We conclude that the beta-turn region of the insulin molecule normally possesses considerable flexibility, which may be necessary for it to assume a conformation commensurate with high biological activity. If this is the case, [B21 D-Glu]insulin may exhibit a stabilized geometry similar to that of natural insulin when bound to the insulin receptor. PMID- 1910464 TI - Biotinylation of transducin and G0 from bovine brain. AB - A method is described for modifying G proteins with biotin. With transducin, better results were obtained with the amino group-specific derivative BXNHS (biotinyl-epsilon-aminocaproic acid N-hydroxysuccinimide ester) as compared to the -SH-group specific reagent MBB (maleimidobutyrylbiocytin). Modification occurred under conditions preserving functional activity: Interaction of the biotinylated transducin with rod outer segment membranes was shown by its light dependent association and by a GTP gamma S-binding assay. G0 from bovine brain was also biotinylated under conditions preserving its activity. Biotinyl-alpha 0 was shown to bind to a streptavidin Sepharose matrix. Biotinyl-G proteins, therefore, are proposed as tools for extracting proteins (receptors and effector systems), which interact under specific conditions with G proteins. PMID- 1910465 TI - Proton NMR studies of angiotensin II and its analogs in aqueous solution. AB - The 1H nuclear magnetic resonance (NMR) spectra of angiotensin II (Asp-Arg-Val Tyr-Ile-His-Pro-Phe) and five of its octapeptide analogs as well as angiotensin I (Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu) and angiotensin III (Arg-Val-Tyr-Ile His-Pro-Phe) in aqueous solutions (90% H2O/10% D2O) were completely assigned by two-dimensional COSY and ROESY experiments. All of the peptides give rise to two distinct sets of signals. The minor set accounts for about 5% of the total population below pH 5.5 and increases to 12-20% around pH 7.0. The two sets of signals result from a cis-trans isomerization of the His-Pro peptide bond with the major resonances arising from the trans isomer. One analog in which the Pro is replaced with a D-Pro displays a very different isomerization behavior. The measured coupling constants JNH-alpha CH, the temperature dependence of the amide proton shifts and the relative intensities of the intraresidue and sequential NH alpha CH ROEs, are all indicative of an extended backbone conformation for ANGII. However, some evidence for the existence of conformers with local structure involving preferred sidechain positions for the Tyr, His, Phe, and the carboxyl group of the Phe was found, particularly in the ROESY and pH-titration experiments. Moreover, pH effects and the unusual amide exchange behavior of the Arg epsilon NH suggests the presence of interactions between the Asp and Arg sidechains of ANGII. At low temperatures the Arg guanidinium NH2 protons were detected as two broad peaks which are related by sizeable exchange peaks in ROESY experiments. This behavior could be useful as a general probe for the study of Arg sidechain mobility and accessibility in other peptides and proteins. PMID- 1910467 TI - Positioning and immobilization of patients undergoing radiation therapy for Hodgkin's disease. AB - The prognosis for patients with Hodgkin's disease is largely determined by the initial management, therefore, special attention must be given to the precision of the often complex treatment in these relatively young and curable patients. Positioning and immobilization is extremely important and may have a role in the final outcome of the treatment. Alpha Cradles, along with laser alignment systems, have been routinely used for these patients in our institution for approximately 10 years. Despite these efforts, difficulties are encountered in precisely reproducing the setup. A modification was therefore made to an Alpha Cradle to include an arm support with handles that fix the position of the patient's elevated arms during the treatment. This modification provides improved repositioning and alignment of the patients, which may have an impact on the final outcome of the treatment. The positioning device also offers improved patient comfort, and, as a result, reduced patient motion as evidence by the reduced number of adjustments required when port films are examined. Additionally, the described technique reduces the risks of over- or underdosage at the junction between the mantle and the para-aortic fields. PMID- 1910466 TI - Aldimine to ketoamine isomerization (Amadori rearrangement) potential at the individual nonenzymic glycation sites of hemoglobin A: preferential inhibition of glycation by nucleophiles at sites of low isomerization potential. AB - The relative roles of the two structural aspects of nonenzymic glycation sites of hemoglobin A, namely the ease with which the amino groups could form the aldimine adducts and the propensity of the microenvironments of the respective aldimines to facilitate the Amadori rearrangement, in dictating the site selectivity of nonenzymic glycation with aldotriose has been investigated. The chemical reactivity of the amino groups of hemoglobin A for in vitro reductive glycation with aldotriose is distinct from that in the nonreductive mode. The reactivity of amino groups of hemoglobin A toward reductive glycation (i.e., propensity for aldimine formation) decreases in the order Val-1(beta), Val-1(alpha), Lys 66(beta), Lys-61(alpha), and Lys-16(alpha). The overall reactivity of hemoglobin A toward nonreductive glycation decreased in the order Lys-16(alpha), Val 1(beta), Lys-66(beta), Lys-82(beta), Lys-61(alpha), and Val-1(alpha). Since the aldimine is the common intermediate for both the reductive and nonreductive modification, the differential selectivity of protein for the two modes of glycation is clearly a reflection of the propensity of the microenvironments of nonenzymic glycation sites to facilitate the isomerization reaction (i.e., Amadori rearrangement). A semiquantitative estimate of this propensity of the microenvironment of the nonenzymic glycation sites has been obtained by comparing the nonreductive (nonenzymic) and reductive modification at individual glycation sites. The microenvironment of Lys-16(alpha) is very efficient in facilitating the rearrangement and the relative efficiency decreases in the order Lys 16(alpha), Lys-82(beta), Lys-66(beta), Lys-61(alpha), Val-1(beta), and Val 1(alpha). The propensity of the microenvironment of Lys-16(alpha) to facilitate the Amadori rearrangement of the aldimine is about three orders of magnitude higher than that of Val-1(alpha) and is about 50 times higher than that of Val 1(beta). The extent of nonenzymic glycation at the individual sites is modulated by various factors, such as the pH, concentration of aldotriose, and the concentration of the protein. The nucleophiles--such as tris, glycine ethyl ester, and amino guanidine--inhibit the glycation by trapping the aldotriose. The nonenzymic glycation inhibitory power of nucleophile is directly related to its propensity to form aldimine. Thus, the extent of inhibition of nonenzymic glycation at a given site by a nucleophile directly reflects the relative role of pKa of the site in dictating the glycation at that site.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1910468 TI - A technique for evaluating cast foam positioning and immobilization devices used in breast cancer radiotherapy. AB - Patient setup reproducibility when Alpha Cradles* are used is not well documented. A simple technique is described that localizes longitudinal and transverse planes in breast setups utilizing 4 mm lead-sphere markers embedded in a modified HS-2 Alpha Cradle. The markers are positioned in the cradle coincident with the projected simulator central axis crosshair when the x-ray beam is directed vertically down through a setup point on the patient. A reference film recording patient position relative to the Alpha Cradle is taken through the setup point at the end of the simulation procedure. On the treatment machine, the images of the lead markers on the portal film, taken through the same setup point, indicate longitudinal and transverse planes. These planes are then used to correlate and quantitate the reproducibility of the original reference planes. This technique is easily initiated, and when used in conjunction with a careful analysis of conventional treatment portal films, is very useful in determining the accuracy of patient repositioning in the Alpha Cradle, and precise field placement. Results of a study utilizing a modified HS-2 Alpha Cradle will be presented. PMID- 1910469 TI - Immobilization techniques and dosimetric aspects for pituitary tumors. AB - Twelve percent of all intracranial tumors arise in the pituitary fossa. The management of pituitary tumors is a complex process that may combine several treatment modalities including radiation therapy. Minimizing patient movement during the course of radiation therapy treatment is imperative to ensure both the delivery of the prescribed dose to the small target volume and to minimize the radiation dose to critical structures. Several alternative types of immobilization devices are being used for this purpose; these include biteblocks, thermal plastics, and polyurethane molds (Alpha Cradle). The advantages and disadvantages of each of these devices are reviewed and the fabrication process of the pituitary immobilization mold that we are currently using is described. Dosimetric aspects of the treatments using these devices is addressed. PMID- 1910470 TI - Results of neutron radiosurgery for inoperable arteriovenous malformations of the brain. AB - Twenty patients with inoperable arteriovenous malformations (AVMs) of the brain were treated with neutron radiosurgery. A 50 MeV cyclotron was used to deliver 9 Gy in a single fraction through 7 to 14 isocentric portals. The size and shape of the portals were customized to each treatment site. Nineteen patients have been followed for a median duration of 24 months following neutron radiosurgery. A radiographically demonstrable partial response was seen in 8 patients (42%). No complete responses were observed. There has been one post-treatment hemorrhage, no fatalities, and no evidence of radiation toxicity. The low response rate and absence of toxicity suggest that the appropriate dose for neutron radiosurgical treatment of AVMs is higher than the dose of 9 Gy at isocenter used in this initial study. PMID- 1910471 TI - Standardization of dosimetry chart checks. AB - This paper reports on a standardized report form that can be used to analyze dose error rates from radiation therapy. An error classification scheme of Types 1 to 5 was developed to indicate increasing severity of errors. Type 1 (charting errors) and Type 3 (daily dose errors) were the most prominent types. Dosimetry errors were reduced by using the results of the reports to correct operating procedures. Type 1 error rates decreased from 17% initially to an average of 3.9%. An average error rate of 1.7% for Type 3 dose errors was found to be consistent with normal operation. Use of the report form is useful in documenting and correcting errors and as a reporting record for use in a quality assurance program. PMID- 1910472 TI - Generation of dose calculation data tables using cubic spline interpolation. AB - In order to calculate treatment machine settings for a teletherapy machine (e.g., time or monitor units), tables are usually used for variables such as output factor, TMR, percent depth dose. The tables are often generated from data collected at a few points. A linear interpolation is usually used to generate values between the measured points. This can introduce errors as great as 2% between the calculated and actual data points. Using a mathematical software package a computer can generate smooth, accurate curves that agree with measured values to within a few tenths of a percent. This method is not an averaging type of procedure by which a certain function is chosen and parameters are adjusted to force the function to fit the data as closely as possible, but rather is a procedure that fits curves exactly through the measured data points. PMID- 1910473 TI - Implementation of the three-field electron wraparound technique for extensive recurrent chest wall carcinoma: dosimetric and clinical considerations. AB - Treatment of extensive recurrent chest wall carcinoma is a challenge for the radiation oncologist as well as the physics team responsible for setup, computer planning, and daily reproducibility. While electron arc therapy is desirable, unfortunately, most sites do not have this capability. The alternative method of treatment discussed here involves the use of a three-field electron wraparound technique for the chest wall when electron arc therapy is not available. This technique yields an excellent alternative treatment modality with flexibility to accommodate multiple electron energies to compensate for varying chest wall thickness. An additional anterior photon beam is used when skin lesions extend superiorly to the clavicle and along the proximal aspect of the arm. Computerized tomography (CT) interfaced radiotherapy computer planning is used to precisely calculate the sequential gantry angles, skin gaps for adjacent electron fields, and the appropriate junction moves to create a feathering effect of all overlap areas. Treatment aids include extensive shaping of electron and photon fields and the application of bolus material on all four fields. A Smithers Medical Products' Alpha Cradle is used to make this intricate setup possible, providing patient comfort and daily reproducibility for a more efficient treatment. PMID- 1910474 TI - Pitfalls in dose calculation using a commercial treatment planning computer for Clinac-4 4MV x-ray beam. AB - Dose calculations on a commercial treatment planning computer based on the storage of profile data along a principal axis for Clinac-4 4MV x-ray can lead to significant error in calculated dose in the corners of a large field. These errors are due to the unique nature of the lead flattening filter on Cl-4. A method is suggested to remedy this problem by storing profile data along a diagonal of a large field. PMID- 1910475 TI - Dosimetry and use of an immobilization system for head and neck radiotherapy treatments. AB - The day-to-day reproducibility of planned radiotherapy treatment is an important precondition for achieving good clinical results and reducing toxic effects. This reproducibility is difficult to achieve in the irradiation of head and neck malignancies because of the mobility of this anatomical area. This paper presents a dosimetric study and analysis of the utility of a facial mask immobilization system prepared from an orthopedic glass-fiber bandage. The dosimetric study conducted on a lucite phantom shows that the interposition of one, two, or three layers of the bandage reduces the deep absorbed dose by about 1% at 0.5 cm2, while increasing the absorbed surface dose by 12% (for a field of 15 X 15 cm2 and one layer of bandage) to 46% (for a field of 5 X 5 cm and three layers of bandage). The dosimetric study conducted on a Rando Anderson manikin shows an average increase in the skin dose of about 8% and a maximum increase of about 20%. The good dosimetric results and the practicality of this system of immobilization have persuaded us to propose it as an alternative to the systems currently on the market, which, although rather more sophisticated, are also more expensive. PMID- 1910476 TI - Analysis of field and custom block sizes used in radiation therapy--implications for multileaf collimator design. AB - The sizes of radiotherapy treatment fields using customized low melting point alloy blocks have been analyzed for a broad range of treatment fields in a busy radiotherapy department (i.e., 2,000 new cases per year), from small head and neck fields to large mantle fields. The results of this study show that 90% of the blocked fields have an equivalent field size defined by the collimator less than 26 cm and 80%, less than 21 cm. Measurements of the average size of the customized blocks indicate that along one axis 90% have lengths less than 15.5 cm and 80% have lengths less than 13 cm, while for the other axis, 90% have lengths less than 7 cm and 80%, less than 6 cm. PMID- 1910477 TI - Complexities of the protein kinase C pathway. PMID- 1910478 TI - Activating point mutations of the gsp oncogene in human thyroid adenomas. AB - The gene for the alpha polypeptide chain (alpha s) of the heterotrimeric G protein Gs can be activated to the putative oncogene gsp by specific point mutations at codons 201 and 227. Such mutations have been reported in 40% of human growth hormone-secreting pituitary adenomas and in a single autonomously functioning thyroid adenoma. We examined an archival series of 45 differentiated human thyroid tumors by polymerase chain reaction amplification and oligonucleotide hybridization to identify point mutations at each of the affected codons. Successful amplification was achieved in 38 cases, and activating mutations were identified in 5 of 13 (38%) autonomously functioning adenomas, but in none of 16 nonfunctioning adenomas, six papillary carcinomas, or three follicular carcinomas. Our results confirm that the gsp oncogene is involved in the pathogenesis of autonomously functioning tumors but do not support a role in other thyroid tumors. PMID- 1910479 TI - Analysis of ras DNA sequences in rat renal cell carcinoma. AB - The DNA sequences for Ha-, Ki-, and N-ras were determined in six cell lines derived from independent rat hereditary renal cell carcinomas (RCC). Genomic regions encompassing codons 12, 13, and 61 of Ha-ras, Ki-ras, and N-ras, and codon 117 of Ha-ras were PCR amplified and directly sequenced. The DNA sequences of Ha-ras and Ki-ras were normal in all lines tested, as were the codon 12 and 61 sequences of N-ras. However, DNA sequence variations that could code for amino acid substitutions were observed in codons 13, 14, and 18 of N-ras in all the lines. The codon 13 Gly----Val alteration observed was consistent with activating N-ras mutations previously reported. When normal kidney DNA from rats with the hereditary tumor syndrome was sequenced, the same N-ras sequence variations observed in the tumor lines were found. DNA from outbred Long-Evans and inbred Fischer rats also had the altered N-ras sequences. The variant N-ras sequence was not observed in PCR-amplified N-ras cDNA from the RCC lines. Thus, tumor associated activation of ras oncogene appears to be an infrequent event in spontaneous rat RCC. In addition, these data indicate that rats contain an N-ras DNA polymorphism that appears to be a species-specific anomaly. PMID- 1910480 TI - Identification of RB and p53 mutations in mouse lymphoma cell lines. AB - We analyzed the genomic structure and mRNA of the RB and p53 genes in four mouse lymphoid leukemia cell lines (DL-1, DL-5, DL-8, and DL-12). Although no gross structural alteration of the RB gene was observed in any cell line, abnormalities of RB mRNA were detected in at least two cell lines. RB mRNA expression was greatly reduced in DL-12. In addition, cloning and sequencing analysis of the RB cDNA revealed that the RB mRNA in DL-8 had a 276-nucleotide deletion presumably consisting of exons 10, 11, and 12, suggesting that altered splicing resulted in the loss of these exons. Analysis of the p53 gene indicated that DL-5 had a deletion in both alleles and expressed a smaller mRNA. These results suggest that mutations of the RB or p53 genes, or both, are associated with lymphoid leukemogenesis in mice. PMID- 1910481 TI - Transient expression of the cloned mouse c-Ha-ras 5' upstream region in transfected primary SENCAR mouse keratinocytes demonstrates its power as a promoter element. AB - The mouse Ha-ras oncogene is activated by point mutation and overexpressed in developing papillomas during two-stage skin carcinogenesis in SENCAR mice. One of our research aims is to characterize the factors regulating Ha-ras gene expression at the transcriptional level in SENCAR mouse epidermis. Towards this goal, we sequenced 1400 bp of the 5' upstream region of the mouse Ha-ras gene so as to characterize various cis-regulatory elements present in the gene. We identified seven sites with the proper consensus sequence for binding the SP1 transcription factor and three potential binding sites for the CTF-1 factor. In addition, we located a 13-base sequence with 92% homology to the consensus sequence for an estrogen response element and two hexamers with consensus sequences identical to the core sequence of the glucocorticoid response element. A series of transient gene expression vectors was constructed in which various regions of the mouse Ha-ras 5' upstream region were fused to the chloramphenicol acetyltransferase (CAT) gene. These expression plasmids were transfected into newborn and adult primary SENCAR epidermal cells, the epidermal cell population that presumably contains the stem cells involved in two-stage skin tumorigenesis. Transient gene expression assays carried out after 48-72 h indicated that a 2.3 kb Ha-ras 5' fragment produced CAT activity comparable to that produced by pSV2CAT and pdolCMVCAT, both of which are plasmids with strong viral promoters and enhancers driving CAT gene expression. Maintenance of transfected keratinocytes under both nondifferentiating (0.05 mM calcium) and differentiating (1.2 mM calcium) culture conditions demonstrated that the mouse Ha-ras upstream region was relatively unresponsive to changes in calcium concentration in transient expression assays carried out in either newborn or adult keratinocytes. Our results demonstrated the power of the cloned mouse Ha-ras promoter and upstream region in driving transient gene expression after transfection into primary keratinocytes. PMID- 1910482 TI - Role of growth hormone in the regulation of the c-myc gene during progression of sex-differentiated rat liver carcinogenesis in the resistant hepatocyte model. AB - In this study, we extended the previous observations of a growth hormone regulated sex difference in hepatic c-myc expression in the resistant hepatocyte model during the selection/promotion phase, when sex differences in growth rate of enzyme-altered foci are first identified, to studies of the regulation of this gene during later stages of hepatocarcinogenesis. The expression of the c-myc gene was studied in preneoplastic nodules, hepatocellular carcinomas, and the corresponding surrounding livers of male and female Wistar rats treated according to the resistant hepatocyte model. In males, nodules isolated 8 and 11-12 mo after initiation and hepatocellular carcinomas exhibited a 2.5- to threefold higher c-myc expression than the surrounding liver. In females, no increase in c myc expression was observed in nodules 8 mo after initiation, while nodules isolated after 11-14 mo and tumors showed a twofold and threefold increase, respectively, when compared with the surrounding tissue. Increased transcription of the c-myc gene was observed in nuclei from male nodules isolated 11 mo after initiation compared with nuclei from the surrounding liver. The difference in transcription between male nodules and surrounding tissue is similar for the first and second exon of the gene. Continuous infusion of growth hormone to nodule-bearing male rats 8 and 11 mo after initiation decreased c-myc expression in the surrounding tissue and downregulated the expression in 8-mo nodules to the level in the surrounding liver. No significant decrease in response to growth hormone treatment was seen in 11-mo nodules. In hypophysectomized nodule-bearing males, nodular c-myc remained upregulated. Taken together, the data showed that the sex difference in c-myc expression was maintained during a large part of the progression period. Furthermore, the loss of growth hormone regulation of the c myc gene in advanced male nodules indicated an escape from normal regulatory mechanisms during progression. These findings might reflect a role for the c-myc gene in sex-differentiated rat liver carcinogenesis. PMID- 1910483 TI - Spectrum of cis-diamminedichloroplatinum(II)-induced mutations in a shuttle vector propagated in human cells. AB - The supF gene of the shuttle vector pZ189 was used as a target for the study of mutations induced by cis-diamminedichloroplatinum(II) (cis-DDP). Normal human repair-proficient fibroblasts and cis-DDP repair-deficient xeroderma pigmentosum (XP) cells were used as host cells to study the effect of cis-DDP on the inhibition of shuttle vector replication and mutagenesis. Transfection of cis-DDP treated pZ189 into normal and XP cell lines resulted in a marked increase in the mutation frequency and a decrease in the replication efficiency of the vector. However, these effects were much greater for the plasmid propagated in XP cells. Atomic absorption spectroscopy showed that six to eight Pt-DNA adducts per plasmid were necessary to inhibit plasmid replication by 50% in normal cells. In contrast, only one to two Pt-DNA adducts were necessary to inhibit replication of the plasmid by 50% in XP cells. Analysis of mutation sites demonstrated that cis DDP treatment resulted primarily in single and double mutations separated by one base and limited to a few locations within the 85-bp mature tRNA. Propagation of the cis-DDP-treated vector in either normal or XP cells led to predominantly transversion mutations at AGA, AGG, and GAG sites and a cis-DDP-associated deletion of 174 bp. Although mutations occurred at target sites for cis-DDP adduct formation, there was no correlation between sites of mutation and the most frequent sites of adduct formation. PMID- 1910484 TI - Cytochrome P4501A2 constitutively expressed from transduced DNA mediates metabolic activation and DNA-adduct formation of aromatic amine carcinogens in NIH 3T3 cells. AB - We transduced mouse cytochrome P4501A2 DNA into NIH 3T3 cells by retrovirus mediated gene transfer. The capacity of the transduced cytochrome P4501A2 for metabolic activation and DNA-carcinogen adduct formation of aromatic amine carcinogens was investigated. Clones of NIH 3T3 cells that constitutively express cytochrome P4501A2 and controls were exposed to a prototype food-derived carcinogenic heterocyclic amine, 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), and an aromatic amine, 2-acetylaminofluorene (AAF), and their genomic DNAs were analyzed for adducts by 32P-postlabeling assays. Kinetic analysis of DNA carcinogen adducts indicated that adduct formation was dependent on the level of the enzyme, the dose of carcinogen, and the duration of exposure. Addition of 7,8 benzoflavone, an inhibitor of P4501A2, blocked both the enzyme activity and DNA adduct formation, indicating the specific role of P4501A2 in metabolic activation and adduct formation. Three specific IQ-DNA adducts were detected in cells expressing P4501A2. Fingerprints of the in situ DNA adducts were similar to those of the in vivo adducts in rodent hepatic DNA after the administration of IQ. A single AAF-DNA adduct was observed in cells exposed to AAF, but other minor adducts were also detected in vivo. These results show that cells expressing constitutive levels of single cytochrome P450s provide an excellent in situ model system for analyzing the catalytic specificity, metabolic activation, and genotoxicity of putative toxic, mutagenic, and carcinogenic substances. PMID- 1910485 TI - Levels of pros-methylimidazoleacetic acid: correlation with severity of Parkinson's disease in CSF of patients and with the depletion of striatal dopamine and its metabolites in MPTP-treated mice. AB - The cerebrospinal fluid (CSF) levels of pros-methylimidazoleacetic acid (p-MIAA) in thirteen medication-free patients with mild to moderate Parkinson's disease were highly correlated (Spearman's rho = 0.749, p less than 0.005) with the severity of signs of the disease as scored on the Columbia University Rating Scale. Levels of p-MIAA in males (n = 8) and females (n = 5) were each significantly correlated with scores of severity (rho = 0.78, p less than 0.05 and rho = 1.0, p less than 0.05, respectively). In C57BL/6 mice treated with 1 methyl-4-phenyl-1,2,3,6-tetra-hydropyridine (MPTP), levels of p-MIAA were significantly correlated with the depleted levels of dopamine (r = 0.85, p less than 0.01), homovanillic acid (r = 0.79, p less than 0.02), 3,4 dihydroxyphenylacetic acid (r = 0.84, p less than 0.01) and norepinephrine (r = 0.91, p less than 0.002) in striatum, but not in cortex of the same mice. No such correlations were observed in either striatum or cortex of saline-treated control mice. Mean levels of p-MIAA in CSF did not differ significantly between patients and age-matched controls; and mean levels of p-MIAA in striatum did not differ between MPTP-treated mice and controls. The simplest hypothesis to account for these strong correlations in the absence of differences in mean levels of p-MIAA is that accumulation of p-MIAA [or process(es) that govern its accumulation] influences a failing nigrostriatal system. It is also possible (in analogy with findings in other diseases and with other drugs) that measurements of the putative metabolite(s) of p-MIAA may distinguish the patients and the MPTP treated mice from their respective controls. Elucidation of the processes that regulate formation and disposition of p-MIAA in brain and information on the neural effects of p-MIAA, its precursors and its putative metabolites may yield insight into factors that regulate the progression of Parkinson's disease, and may shed additional light on the cause(s) of this disease. PMID- 1910486 TI - Differential effect of L-threo-3,4-dihydroxyphenylserine in pure autonomic failure and multiple system atrophy with autonomic failure. AB - Treatment with L-threo-3,4-dihydroxyphenylserine (L-threo-dops), a synthetic precursor of norepinephrine, significantly increased upright blood pressure in patients with multiple system atrophy but had no effect on the upright blood pressure of patients with pure autonomic failure. These results suggest that the site of action of L-threo-dops is central and that its pressor effect requires intact peripheral sympathetic neurons. PMID- 1910487 TI - The electrophysiological properties of substantia nigra pars compacta neurones recorded from 6-hydroxydopamine lesioned guinea-pigs in vitro. AB - Intracellular recordings were made from substantia nigra pars compacta neurones in vitro from animals with partial unilateral 6-hydroxydopamine lesions of the nigrostriatal tract. Lesions were assessed and grouped according to the severity of the striatal dopamine depletion. No differences were seen between neurones from control and lesioned side nigrae as regards their membrane properties, firing rates, burst activity or percentage of quiescent neurones in any of the lesioned categories. It is concluded that following partial lesioning, the remaining substantia nigra zona compacta neurones in vitro, are functioning normally. PMID- 1910488 TI - [Comparison of 2 methemalbumin measurements and of free hemoglobin in view of their value in the differential diagnosis of edematous and hemorrhagic pancreatitis]. AB - Methemalbumin was estimated by means of electrophoresis and the method of Walberg, respectively in 59 patients (25 pat. with edematous, 34 patients with hemorrhagic pancreatitis) partially over three days. In addition the estimation of free hemoglobin in ascites has been carried out. By both approaches of methemalbumin estimation there was no differentiation of the two pancreatitis forms possible. Though the method of Walberg was much more sensitive especially in the serum its specificity was correspondingly lower. The tendency to a correlation of the methemalbumin-concentration to the severity of the course of the disease could be observed. Such a correlation has been proved statistically for the free hemoglobin. PMID- 1910489 TI - [Foreign bodies in the bile ducts and their endoscopic removal]. AB - The diagnostic and therapeutic management is described in four cases with foreign bodies of the biliary tract: ball of thread, T-bougie, shell splinter, peel of greens. The possibilities of therapeutic endoscopy are emphasized. PMID- 1910490 TI - [Lipid metabolism disorders in primary biliary cirrhosis (PBC)]. AB - 40 women, average age 52.5 years, with varying stages of primary biliary cirrhosis, were observed. One third of them suffered from a mild anaemia, mean plasma concentrations of ALAT were increased four times and those of AP six times. Despite the hepatocellular damage products of the liver synthesis such as transport proteins or coagulation factors were found to be normal or enhanced. 60% of the patients had a hypercholesterolaemia. The risk factors low density lipoprotein (LDL)- and very low density lipoprotein (VLDL)-cholesterol showed normal levels, but the protective factor high density lipoprotein (HDL) cholesterol was clearly increased. Apart from the low blood pressure in most of the patients and the absence of other risk factors these observations explain, why patients with PBC and hypercholesterolaemia don't usually develop arteriosclerotic complications. Only in case of severe cholestasis a lipid constellation comes into being accompanied by high risk for the blood vessels, but in these cases the terminal stage of PBC limits the survival. Positive correlations between markers of cholestasis and lipid parameters let an enhanced production and simultaneous impaired excretion of cholesterol be assumed. PMID- 1910491 TI - [Possibilities for optimization of radiotherapy of esophageal carcinoma through measurement of the oncoradiogenic enzyme peak of glucosephosphate isomerase]. AB - In 20 patients with oesophageal carcinoma blood samples were taken after the first irradiation and the activity of the glycolytic enzyme glucose-6-phosphate isomerase was measured. In all patients there occur GPI peaks at reproducible times. The height of the enzyme peak occurring 15.5 to 19.5 hours p.irr. expresses a significant dependence on tumour size and irradiation dose. The frequency of a late occurring enzyme peak depends on the appearance of regional lymph node metastases. Possible sources of the enzyme peaks are discussed from a radiobiological point of view and the meaning of such enzyme peaks for the optimization of radiation therapy is pointed out. PMID- 1910492 TI - [Circulating lymphocyte subpopulations in patients with Crohn's disease]. AB - Circulating lymphocytes were enumerated in 25 patients with Crohn's disease and in 43 healthy donors by immunofluorescent staining using monoclonal antibodies for T cell surface phenotypic markers (CD 3, CD 4, CD 8) or for surface immunoglobulin of B cells (mu-chain). Proportions of peripheral T cells and percentages of T cell subsets in Crohn's disease were not significantly different from those in controls. For analyzing the lymphocytes for the expression of activation associated antigens (HLA-DR, CD 25) we found increased numbers of activated lymphocytes during acute exacerbation, whereas, in remission, the population of activated lymphocytes was in the upper normal range. The results leads to the conclusion that the assessment of activated lymphocytes may serve as a parameter in the evaluation of the activity of Crohn's disease. PMID- 1910493 TI - [The effects of verapamil and nifedipine on the biotransformation of model substances and on the indocyanine green elimination]. AB - Twelve healthy subjects received a cocktail of model substances (containing metamizol: 1000 mg, caffeine: 200 mg, sulfadimidine: 500 mg, and debrisoquine: 10 mg) alone and on the fifth day of a five day therapy of oral verapamil (3 x 80 mg) or nifedipine (3 x 20 mg) to assess the effect of verapamil and nifedipine on hepatic biotransformation. To investigate liver blood flow intravenous indocyanine green (0,5 mg/kg) was given 12 and 1 hours after oral verapamil (80 mg) or nifedipine (20 mg). In the presented study an influence of verapamil and nifedipine treatment on the hepatic drug oxidizing system was not observed. The elimination half-life of intravenous indocyanine green was only 1 hour after oral nifedipine (20 mg) significantly decreased. 12 hours after nifedipine (20 mg) or verapamil (80 mg) as well as 1 hour after verapamil (80 mg) treatment no change in indocyanine green elimination was observed. The estimated increase of liver blood flow after oral nifedipine may cause increased absorption of other oral administered drugs and may accelerate hepatic elimination of drug with high hepatic extraction rate. 6 fast an 6 slow acetylators were found. This classification did not change after nifedipine or verapamil therapy. PMID- 1910494 TI - [Influence of the ileum on the regulation of gastrointestinal motility]. AB - Under normal conditions a "physiologic malabsorption" and thus nutrients in the lower small intestine in the late postprandial state can be observed in humans. To study the effects of "physiologic" quantities of nutrients in the distal small intestine on upper gastrointestinal motor functions, 9 healthy subjects were intubated with an oro-ileal multi-lumen tube. The continuous perfusion of the duodenum with essential amino acids induced a fed motility pattern. In 12 out of 14 cases additional ileal perfusion with carbohydrates (60 kcal), but not with saline, converted the fed motility pattern to a pattern characteristic of the interdigestive state. These findings suggest that the ileum takes part in the late postprandial regulation of proximal gastrointestinal motor functions in humans. PMID- 1910495 TI - [Prognostic parameters in peptic ulcer disease]. AB - Tendency of peptic ulcer to frequent recurrence and spontaneous healing as to life-threatening complications are apart of the natural history of ulcer disease. In a retrospective study of 7 years, we examined 27 simple factors for their prognostic value by 218 patients suffering from ulcer disease which were diagnosed by fibroscopy. The interpretation with help multi analysis, the variant and discriminant analysis showed by patients with stomach ulcer that, the prognosis of the combination between renunciation of nicotine the begin of the disease until 30th years of the people, more than three foods daily, stomach cancer in the family, blood group A and left finger position would be suitable. The prognosis was better for patients with duodenal ulcer who have nicotine abstinence, childlessness negative history of the family with view to ulcer disease, blood group 0, positive Rh-factor and the working time. PMID- 1910496 TI - Secretin provocation ultrasonography in the diagnosis of papillary obstruction in pancreas divisum. AB - The diagnostic value of secretin provoked abdominal ultrasound was studied on 34 patients with pancreas divisum and on 20 control subjects. The patients received a 1.0 unit/kg body weight dose of secretin. The degree of ductal expansion and the time required to return to the initial state were registered and these values were compared to the clinical diagnosis. The control subject's ductal diameters prior to secretin administration were 1 mm in all cases (maximum expansion 2 mm, return to the initial value within 10 minutes). The pancreas divisum patients could be placed in two groups based on their initial ductal diameter. Fourteen patients had initial ductal diameters of 2 mm or greater (A group mean +/- SD: 2.4 +/- 0.3) while 21 patients had an initial value of less than 2 mm (B group; 1.7 +/- 0.3). Following secretin administration the ductal diameter of the A group's patients increased on average +/- SD to 1.3 +/- 0.5 times the initial value and in the B group 3.2 +/- 1.1 times the initial value (p less than 0.01). In the A group the ductal diameter returned to it's initial value within 10 minutes while it took 35 minutes for the same to occur in the B group. A relationship can be observed between the clinical diagnosis, the initial ductal diameter, the degree of expansion following secretin administration and the time required to return to the initial state. PMID- 1910497 TI - [Clinical, infrared spectroscopic and chemical analysis of bile duct and gallbladder stones]. AB - By means of concrements, which were obtained endoscopically by extraction from the bile duct, and of gallstones, which were given the patient by the surgeon on the occasion of the gallbladder operation, we performed stone analyses with the aid of infrared spectroscopy and compared them correlatively with clinical and case history data. The paper focussed on the detection of the stony structure of choledochal concrements, separated into stone core and stone mantle. A method for the reliable differentiation of stones left (residual stones) from new formations (recurrent stones) in the bile ducts has not been possible to date. Thus, the burning question of the surgeon cannot be answered with certainty. However, there is no doubt about surgical suture material as incrustation core for a pigment stone in terms of a true recurrent stone, which poses a real challenge to biliary tract surgery. PMID- 1910498 TI - [Studies on varietal resources of Chinese medicinal plants and their preservation]. AB - The paper reviews the status of varietal resources of Chinese medicinal plants in China. The existing problems are analysed. Characteristics of these resources are dealt with. The results have shown that the study of varietal resources of Chinese medicinal plants must be strengthened for facilitating their production. Methods of varietal preservation of these plants are also discussed. PMID- 1910499 TI - [Textual and herbal studies of Chinese drug xiebai]. AB - After some herbalogical studies and on-the-spot investigation, the authors have found out that the Chinese drug xiebai, which was used in ancient times, is not Allium macrostemon but A. chinense (Liliaceae). It was after the Qing Dynasty that A. macrostemon came into use as xiebai. The authors thus suggest that both A. chinense and A. macrostemon be taken as the original herb of xiebai. PMID- 1910500 TI - [Systematic exploitation of regional resources of Chinese herbal drugs]. AB - This paper advances the concept of regional resources of Chinese herbal drugs and the policy-making pattern for the systematic exploitation of these resources. The AHP is used for the first time in the systematic study on the resources of Chinese herbal drugs in the Qingchenghou mountains, Sichuan, with the desired result that proves beneficial to the spheres of society, economy and ecology. PMID- 1910501 TI - [Physico-chemical identification of seven snake-drugs]. PMID- 1910502 TI - [Methods of cryopreservation of pollen in Fritillaria thunbergii Miq]. AB - The effects of cryomethods, cryoprotectants, pollen age and pollen water content on the viability of pollen in Fritillaria thunbergii after cryopreservation were studied. The viability came highest (56.4%) when pollen of the flowering day (20% pollen water content) was treated by step-cooling. Hybridization in the fields showed that cryopreserved pollen could go to seed as well. PMID- 1910503 TI - [Distribution and activity regularities of medicinal Mojiang centipedes in Yunnan Province]. AB - A study has been made on the distribution, living environment and behavior characteristics of medicinal Mojiang centipedes in Yunnan Province. The result has shown they are active between mid-March and late October every year. During this time, the temperature is 18-23 degrees C, moisture 75-85 percent, precipitation 50-280mm, sunshine 115-225 hours and evaporation 100-200mm. PMID- 1910504 TI - [Effect of drug processing on shaoyao gancao decoction]. PMID- 1910505 TI - [Leukogenic effect and antioxygen radicals function of fufang wuzi yanzong pills]. AB - Fufang wuzi yanzong pills have strong leukogenic effect on cyclophosphamide induced leukopenia in mice. It can decrease the lipid peroxide (MDA) content of liver in rats and lipofuscin contents of heart and kidney in mice and increase the superoxide dismutase (SOD) activity of liver in rats. PMID- 1910506 TI - [Chemical constituents of Acanthopanax giraldii Harms]. PMID- 1910507 TI - [Chemical constituents of anticancer plant Nyssa sinensis Oliv]. PMID- 1910508 TI - [Isolation and structure determination of echinuline from Veratrum nigrum L. var. ussuriense Nakai]. PMID- 1910509 TI - [Determination of cholesterol in natural bezoar by gas chromatography]. AB - A gas chromatographic method for the determination of free and total cholesterol in natural bezoar has been established in this report. The method is simple, specific and accurate. The free and total cholesterol contents in three kinds of bezoar are between 0.072% to 0.214% and 0.546% to 0.608% respectively. PMID- 1910510 TI - [Studies on warming the middle-jiao and analgesic effect of flos Caryophylli]. AB - The effects of water extract and ether extract of Flos Caryophylli have been investigated by four experimental gastric ulcer models, choleresis in rats, two diarrhea models in mice, two pain stimulations in mice, and acute liver injury induced by CCl4 in rats. The results suggest that the action of Flos Caryophylli on dispelling the cold by warming the middle-jiao and curing abdominalgia is related to its anti-ulcer, choleresis increasing, anti-diarrhea and analgesic functions. PMID- 1910511 TI - [Radioprotective effect of water soluble nonsaponin components in ginseng]. PMID- 1910512 TI - [Effects of semen Ziziphis Spinosae oil and Ziziphis Spinosae extract on the decrease of serum lipoprotein and inhibiton of platelet aggregation]. AB - Our experiments have shown that oral administration of Semen Ziziphis Spinosae oil(SZSO) or Ziziphis Spinosae extract (ZSE) given to quails for 53 days can significantly reduce their TC, LDL and TG and markedly subdue the fatty degeneration in their livers. Also, SZSO pressed into the stomach of rats for five days can conspicuously inhibit their platelet aggregation, while ZSE cannot. PMID- 1910513 TI - [Effects of liuwei dihuang decoction and its compositions on blood sugar and glycogen in mice]. AB - We have studied the effects of liuwei dihuang decoction (LDD) and its compositions on blood sugar and glycogen in mice, and found that sanbu, shanzhuyu danpi and shanyao-fuling matched pairs can reduce the level of blood sugar, while LDD, sanbu, shudi-zexie and shanzhuyu-danpi matched pairs can increase the content of glycogen in liver. The present study is only a preliminary research on the effects of LDD and its compositions on the metabolism of sugar in the body. PMID- 1910514 TI - What the patient thought. PMID- 1910515 TI - Quality assurance--a study in radiography. PMID- 1910516 TI - Introducing a radiographic quality control system at Crawley District General Hospital. PMID- 1910517 TI - How good is the erbium filter? PMID- 1910518 TI - The NHS act and the move to trust status. PMID- 1910519 TI - The use of stable isotopes for food web analysis. AB - General aspects in isotope biogeochemistry was summarized with emphasis on delta 15N and delta 13C contents in plants and animals in natural ecosystems. In the estuary, the variation of isotope ratios were principally governed by the mixing of land-derived organic matter, marine phytoplankton, and seagrasses. A clear cut linear relationship between animal delta 15N and its trophic level was obtained in the Antarctic food chain system. Several current efforts to use the stable isotopes for food web analysis were demonstrated for some terrestrial and marine systems as well as human food web. PMID- 1910520 TI - Stable carbon isotopes and the study of prehistoric human diet. AB - Mass spectrometric analysis of the stable carbon isotope composition (13C/12C or delta 13C) of bone collagen from human remains recovered at archaeological sites provides a direct chemical method for investigating dietary patterns of prehistoric human populations. This methodology is based on the facts that (1) different food items within the human diet have distinct delta 13C values, and (2) the delta 13C value of human bone collagen is determined by the delta 13C value of the diet. Studies of the development of subsistence patterns based on corn agriculture, one of the most significant developments in North American prehistory, can benefit from the use of stable carbon isotope techniques because corn has a high delta 13C value relative to other components of the human diet. Measurements of delta 13C of bone collagen from prehistoric human skeletal remains from southeastern Missouri and northeastern Arkansas indicate that intensive corn agriculture began in this region around A.D. 1000, that the incorporation of corn into the human diet was a rapid phenomenon, and that 35 to 77% of the human diet from A.D. 1000 to A.D. 1600 consisted of corn. Results from an isochronous population in southeastern South Dakota (A.D. 1400) suggest that 78 to 90% of the diet of this group consisted of corn, with no difference between males and females. Coupled with more traditional archaeological methods, stable carbon isotope analysis of bone collagen can significantly enhance reconstruction of dietary patterns of prehistoric humans. PMID- 1910521 TI - Bioavailability of dietary minerals to humans: the stable isotope approach. AB - A number of minerals contained in foods are essential nutrients for humans, animals, and/or plants. While most vitamins are very well absorbed, most essential minerals are not. Usual absorption of minerals ranges from less than 1% to over 90%. The bioavailability of dietary minerals must be considered when determining whether the diet contains enough, too little, or too much. By using stable isotope tracers as labels, the metabolic fate of minerals in a specific day's diet, a specific meal, or a food can be distinguished from minerals from other sources and followed. A number of mass spectrometric methods have been used to measure stable isotopes. Magnetic sector, thermal ionization mass spectrometry (TIMS) is used routinely in our laboratory to study bioavailability of Zn, Cu, and Fe. Other mass spectrometric methods that are less precise, but useful for many applications requiring isotopic determinations include quadrupole TIMS, inductively coupled plasma mass spectrometry (ICP/MS), and fast atom bombardment mass spectrometry (FAB/MS). One of the major advantages of stable isotope studies is that multiple isotopes of the same mineral can be used simultaneously and multiple minerals can be studied simultaneously. The use of stable isotopes for studies of bioavailability of minerals in foods has gained widespread interest in recent years. The approach is expected to be applied to an increasing number of food science and nutrition problems in the future. PMID- 1910522 TI - Confirmation of trace level residues in the food supply. AB - With the recent proliferation of mass spectrometric methods available for the identification and confirmation of various compounds in different environmental matrices, it is timely to address the criteria desirable in a regulatory sample case. The emphasis of this review is on the experimental process of confirmation at concentration levels in the range of low parts per million (ppm) to parts per trillion (ppt). At such levels, various data manipulations or alternate choices of approaching the analytical problem of confirmation must be employed to ensure an acceptable result. The problems experienced when dealing with nanogram levels in analysis are much more complex than when recording a mass spectrum of an ample supply of a reference standard. This review reflects an interpretation of the developing status of confirmation since there does not yet exist "accepted criteria". PMID- 1910523 TI - Aflatoxins in food: occurrence, biosynthesis, effects on organisms, detection, and methods of control. AB - Aflatoxins are secondary metabolites produced by species of Aspergilli, specifically Aspergillus flavus and Aspergillus parasiticus. These molds are ubiquitous in nature and grow on a variety of substrates, thereby producing aflatoxins. Aflatoxins are of great concern due to their biochemical and biological effects on living organisms. In this article, the occurrence of aflatoxins, their biosynthesis, factors influencing their production, their effects on living organisms, and methods of detection and control in food are reviewed. Future areas of research involving mathematical modeling of factors influencing aflatoxin production and alternative methods of control, such as modified atmosphere packaging, are also discussed. PMID- 1910524 TI - Phenolic compounds and polyphenoloxidase in relation to browning in grapes and wines. PMID- 1910525 TI - Studies of adenovirus subtypes and down-regulation of HLA class I expression: correlations to natural-killer-mediated cytolysis. AB - Natural killer cell (NK) cytotoxicity historically has been accepted to be unrelated to major histocompatibility complex (MHC) expression. However, recent studies have indicated that a decrease in MHC antigen expression leads to a concomitant increase in NK cytotoxicity. We have, therefore, studied the alteration of HLA class I expression by 6 types of adenovirus in the human cell line HEp-2. We conclude that for the 6 types of adenovirus tested, HLA class I expression and NK cytotoxicity are not interrelated. PMID- 1910526 TI - Matrix proteins induce neuroblastoma cell differentiation without altering cell growth. AB - The maturation of embryonal neural crest cells is thought to be regulated in part by the milieu into which these cells migrate. Neuroblastoma (NB) is a tumor of very early childhood that is thought to arise in association with the arrested differentiation of embryonal neural crest cells. In culture, neuroblastoma tumor cells differentiate in the presence of retinoic acid, which is also known to influence extracellular matrix protein synthesis. We have cultured neuroblastoma cells on laminin (LN) and fibronectin (FN) substrata to examine the role of extracellular matrix in retinoic acid (RA)-induced differentiation of these tumor cells. These proteins caused morphologic changes in NB cells indistinguishable from those caused by RA. Antiserum to each of these proteins blocked the effects induced by the corresponding protein, but neither antiserum affected the action of RA. Despite the induction of a neuronal morphologic change, matrix proteins did not alter the proliferation of NB cells. These results indicate that LN and FN modulate the differentiation of NB cells without inducing growth arrest and that RA-induced differentiation does not require these matrix proteins. PMID- 1910527 TI - HLA disease association and protection in HIV infection among African Americans and Caucasians. AB - In a previous investigation, we demonstrated an increased progression of overt AIDS in the African American population compared to the Caucasian population as reflected by the significantly lower absolute number of CD4+ lymphocytes detected in the African American population in an earlier study. The present study elucidates some of the possible genetic factors which may contribute to disease association or protection against HIV infection. The HLA phenotypes expressed as A, B, C, DR and DQw antigens were revealed by the Amos-modified typing procedure. NIH scoring was utilized to designate positive cells taking up trypan blue. A test of proportion equivalent to the chi 2 approximation was used to compare the disease population (n = 62; 38 African Americans, 24 Caucasians) to race-matched normal heterosexual local controls (323 African Americans, 412 Caucasians). Significant p values were corrected for the number of HLA antigens tested. HLA markers associated with possible protection from infection for African Americans were Cw4 and DRw6, whereas Caucasians expressed none. Disease association markers present in the African American population were A31, B35, Cw6, Cw7, DR5, DR6, DRw11, DRw12, DQw6 and DQw7, whereas in the Caucasian population A28, Aw66, Aw48, Bw65, Bw70, Cw7, DRw10, DRw12, DQw6 and DQw7 were demonstrated. The highest phenotypic frequency for a disease association marker in the study was for HLA DR5 (62.9%) in the HIV-infected African American population without Kaposi's sarcoma compared to a frequency of 28.9% for the regional control group (p = 0.0012). We conclude that genetic factors do have a role in HIV infection since only 50-60% of those exposed to the AIDS virus will become infected. PMID- 1910528 TI - Tyrosinase expression and melanogenesis in melanotic and amelanotic B16 mouse melanoma cells. AB - Tyrosinase activity, abundance, and mRNA transcription were examined in three sublines of the B16 mouse melanoma. Tyrosinase activity and melanin content were highest in the B16-F1 cells, slightly less in the B16-F10, and markedly lower in the B16-F10-DD cells. No differences in the level of tyrosinase mRNA or protein were found in the three different sublines. Thus, the differences in tyrosinase expression arise from the post-translational modification of the enzyme causing its activation or inhibition. PMID- 1910529 TI - Human recombinant superoxide dismutase protects primary cultured neurons against hypoxic injury. AB - Induction of free radicals and succeeding cascade reactions of lipid peroxidation are known to cause neuronal damage in cases of cerebral ischemia. We studied whether hypoxic stress in vitro induces the formation of these cytotoxic materials, and whether superoxide dismutase (SOD) protects cultured neurons from hypoxic stress. We used human recombinant SOD (rSOD), which is structurally homologous to native human SOD, the only exception being that the N terminus is not acetylated. First, we detected free radicals by means of nitroblue tetrazolium (NBT) and assured that hypoxic stress to the cultured neurons induced the formation of peroxidation materials. Immediately after the hypoxic stress, the neurons showed no reduction from NBT to formazan. Striking NBT coloration of the somata, however, started to appear 30 min after reoxygenation, and the percentage of formazan-positive neurons increased during up to 32 h of the experimental period. About 50% of the neurons stained positively 24 h after hypoxia. This shows that rSOD is needed immediately after reoxygenation. Secondly, we examined whether rSOD exerts a cytoprotective activity against hypoxia. rSOD, with the application of proper treatment which incorporates rSOD into the target neuron, prevents the neuronal damage induced by oxide anions, which plays an important role in acute neuronal death accompanied by hypoxia. It can be concluded that, when intracellularly present in sufficient amounts, rSOD is useful for the treatment of hypoxic damage. PMID- 1910530 TI - The AIMS/GRXVIII cell line: 'spontaneous' transformation of hormonally induced primary cells derived from goat ovarian granulosa. AB - AIMS/GRXVIII is one of the cell lines developed in our laboratory from goat ovarian granulosa cells by luteinizing hormone (LH) stress. Unlike other cell lines in the AIMS/GR series which were contact-inhibited and non-tumorigenic, this one was 'spontaneously' transformed during passage 14 with a doubling time of 20 h. The morphology changed from a spindle shape to epithelial-like. Cultures lost contact inhibition and presented extensive mitotic and chromosomal abnormalities. The cultures secreted progesterone even without LH support after passage 8. The cells developed small tumours of luteal morphology in hamster cheek pouches, though they failed to form colonies in soft agar gel. This is a functional cell line and should be useful in understanding various processes in cell biology like function, signal transduction and mechanisms of cell transformation. PMID- 1910531 TI - Promotion of spheroid assembly of adult rat hepatocytes by some factor(s) present in the initial 6-hour conditioned medium of the primary culture. AB - Adult rat hepatocytes are capable of assembling to form floating multicellular spheroids (spheroids) in a dish with a positively charged surface in primary culture. In this report we show that the conditioned medium of the early time period of the culture exhibited biologically defined activity that promoted the assembly of isolated hepatocytes to floating spheroid. This activity was present only in the initial 6-hour conditioned medium; it was highest in the initial 2 h of culture and gradually decreased over 6 h and was not detected thereafter for 7 days. The conditioned medium appeared to inhibit the disintegration of spheroids that occurred during transfer to a new positively charged dish in the presence of either new or conditioned medium collected after day 4. Furthermore, disintegrated spheroids again assembled to form floating spheroid in the presence of the conditioned medium. Since the activity present in the conditioned medium was linearly dose-responsive to the inoculated viable cell number but not to that of dead cells, some factors responsible for the activity were probably produced by the viable cells during only a short time in culture. PMID- 1910532 TI - Growth studies on fibroblasts of patients with autosomal recessive Friedreich's ataxia. AB - Fibroblasts derived from patients with undisputed autosomal recessive Friedreich's ataxia were examined for their growth characteristics including plating efficiency, proliferation curves and cumulative number of population doublings. In comparison to cells of healthy controls, the cells from ataxia patients showed lower plating efficiency, growth rate and number of cumulative population doublings in these parameters. Cells of heterozygotes showed clonal growth and growth curves in the range of the healthy controls. PMID- 1910533 TI - [Nursing and its professional education]. PMID- 1910534 TI - [Basic curriculum oncologic nursing]. PMID- 1910535 TI - [Report Commission Werner. Diverse reactions at presentation]. PMID- 1910536 TI - [Report Commission Werner. The 21 recommendations]. PMID- 1910537 TI - [Report Commission Werner. 'There should be noticeable improvements in 5 years']. PMID- 1910538 TI - [Searching for a new perspective--anxiety, cancer patients and nurses]. PMID- 1910539 TI - [Mentally handicapped, sexuality and relation (3). Statements by attendants]. PMID- 1910540 TI - [How do I get my freedom back? Analysis of a request for discharge in involuntary admission]. PMID- 1910541 TI - [The professional organization and contact with the practical situation]. PMID- 1910543 TI - [Official start of regional experiments. The way to a coherent educational system]. PMID- 1910542 TI - [Veldwijk in Ermelo--the output is central]. PMID- 1910544 TI - [Nursing care of patients with cancer. Additional education and managing a psychosocial registration form]. PMID- 1910546 TI - [Foundation Kruiswerk Drenthe--limits to integration]. PMID- 1910545 TI - [Staff nurse--Jack-of-all-trades in new shoes]. PMID- 1910547 TI - [Have you been declared competent yet?]. PMID- 1910548 TI - [The nursing mentor as role model. New function in De Grote Beek]. PMID- 1910549 TI - [The diary as communication tool in auditory hallucinations]. PMID- 1910550 TI - Ketobemidone prodrugs for buccal delivery. AB - Various carboxylic acid and carbonate esters of the opioid analgesic ketobemidone were prepared and assessed as potential prodrugs with the aim of obtaining a ketobemidone formulation suitable for buccal or sublingual absorption. The chemical stability, enzymatic hydrolysis and lipophilicity characteristics of the esters were studied using HPLC assay procedures. All esters were rapidly hydrolyzed in human plasma, the half-lives ranging between 0.03 and 1.8 min. A marked enzymatic hydrolysis took place in whole human saliva, the half-lives of hydrolysis being in the range 3-295 min. All esters were more lipophilic than the parent ketobemidone, as determined by octanol-buffer partition experiments and by reversed-phase column chromatography. The relatively high resistance of the sterically hindered 3,3-dimethylbutyryl ester to undergo hydrolysis in saliva combined with its facile plasma-enzyme catalyzed conversion and high lipophilicity makes this ester the most promising prodrug candidate for buccal delivery. PMID- 1910551 TI - Deposition and gastrointestinal transit of conventional sucralfate tablets. AB - Sucralfate was labelled with 99mTc by the stannous reduction method. Tablets were compressed using 1 g of radioactive sucralfate and suitable additives. On the first test day, five fully informed healthy volunteers were given one radioactive tablet of sucralfate each, following 10 h fasting. On the second test day, the sucralfate tablet was given after a standard meal. The gastrointestinal transit of the 99mTc-labelled sucralfate was evaluated using gamma camera technique. The labelling of sucralfate with 99mTc by the stannous reduction method enables the deposition and the transition of sucralfate in the gastrointestinal tract to be monitored. The tablets disintegrated almost immediately after administration and the released sucralfate distributed homogenously over the entire stomach area, in both fasted and fed subjects. Transit from the stomach into the intestine was noted already 10 min after administration in fasted subjects, whereas the gastric emptying of sucralfate was markedly delayed in fed subjects. To achieve a wider and more homogenous distribution in the GI-tract, sucralfate tablets should be taken before eating. PMID- 1910552 TI - Metabolic study of pholcodine in urine using enzyme multiplied immunoassay technique (EMIT) and capillary gas chromatography. AB - A study of pholcodine metabolism in man is reported. Three subjects received a single therapeutic oral dose of 50 mg pholcodine and urine samples were collected as long as a positive opiate response could be detected by EMIT (16-26 days). Pholcodine was found to conjugate with glucuronic acid and 15% (13-17%) of the pholcodine dose was excreted in urine as the glucuronide, and 29% (24-35%) as unconjugated pholcodine. Morphine was detected to be a metabolite of pholcodine and 0.5-1% of the pholcodine dose was excreted as morphine glucuronide. The identity of morphine was confirmed by capillary gas chromatography-mass spectroscopy (GC-MS). PMID- 1910553 TI - [Recurrent respiratory infection in children: its clinical and laboratory evaluation]. AB - Respiratory infections comprise the main cause of medical consultations, and one of two of the first causes of morbidity and mortality in children under five in developing countries. Epidemiological studies have shown that preschool children contract between four and six respiratory infections in the course of a year without this causing any alarm as a deviation from "normality". Yet, the general practitioner and the pediatrician are frequently faced with the dilemma of deciding whether the child who is "always ill" the use of the recurrent infections is, normal or has predisposing conditions to the infections. Among the predisposing conditions for recurrent respiratory infections in children are several host factors, such as immune defense mechanisms and non-immune mechanisms as well as the infections agent and/or the environment. This article is an overview of the clinical and laboratory evaluation findings of children with recurrent respiratory infections. PMID- 1910554 TI - [Kawasaki disease in Mexican children]. AB - The records of 16 cases seen at Mexico Children's Hospital with a diagnosis of KD were reviewed. Mean age was three years; eight were infants, and males were dominant with a ratio of 4.3:1. Two cases occurred in sibling. Evidence of myocarditis was recognized in six, and 12 had coronary anomalies, including five with aneurysms. Two infants with severe coronary disease died, one suddenly with myocardial ischemia, and one with a ruptured aortic aneurysm. Another infant developed severe stenosis of the right coronary artery but remains asymptomatic. Two cases have persistent coronary ectasia and seven are asymptomatic with a normal echocardiogram. Predictors of coronary risk were correlated with clinical outcome. All six cases with 6 or more points had coronary anomalies, two developed giant aneurysms, two died and one has severe coronary stenosis. Of 10 cases with less than 6 points, four did not have coronary involvement, none developed giant aneurysms and none died nor developed severe coronary sequelae. Although KD has been sporadically reported in this country, the present series, the largest from a single institution, firmly establishes the presence of the disease in Mexico. PMID- 1910555 TI - [Kawasaki disease in Mexico: an analysis of 13 cases]. AB - Thirteen clinical charts belonging to children with Kawasaki disease admitted to different hospitals were analyzed. The average age among the children was three years (from nine months to nine years), with a predominance of this disease in males with a ratio of 3.3:1. Echocardiograms were obtained from 10 of the patients; seven showed coronary aneurysms (70%). Other complications seen were myocarditis in six children, and one case in each of the following: arthritis, pericarditis, cardiac failure, coronary thrombosis, hydropic gall bladder and aseptic meningitis. All of the patients recovered successfully; only four of the patients with aneurysms were followed-up with an echocardiogram. The echocardiogram showed the aneurysms to have disappeared in three of the children one to five months later, and the other showed a persistent aneurysm plus dilated myocardiopathy 2.5 years later in the remaining patient. It is worth noting the high incidence of aneurysms (70%) compared to other series (20-65%) which may be due to the suspicion of this diagnosis in only typical cases. PMID- 1910556 TI - [Renin activity in the plasma of premature newborns not ill]. AB - In a prospective manner, sequential plasma renin activity (PRA) was measured in a group of sixteen non-sick premature infants on day 1, 3, 10, 17 and 24 of life. These infants had the following criteria in order to enter the study: breastfeeding, Apgar score greater than 7 at 5 minutes and no medical problems. PRA reached the maximum level by day 10,139 ng/mL/h declining slowly over the next two weeks, but remaining higher than on day one of life. Serum sodium levels were also measured since day one of life; these levels were found low during the entire time of study. We can speculate that our higher PRA values could be related to the physiologic hyponatremia found more accentuated between the third and fourth weeks of life. PMID- 1910557 TI - [The lipid profile in children with nephrosis]. AB - The serum lipid levels of 25 children with SNI of LGM were quantified. All cases showed total cholesterol and triglyceride levels above the 95% percentile for both their age and sex (417 +/- 119 mg/dL and 448 +/- 313 mg/dL respectively). Ninety-two percent of the children showed LBD above the 95 percentile for their and sex (307 +/- 108 mg/dL) and 72% showed LAD in the normal lower limit, under the fifth percentile for their age and sex (26.9 +/- 13.7 mg/dL). A important percentage of the patients showed elevated LMBD (90.8 +/- 61.0 mg/dL). A direct proportional relationship occurred between total cholesterol and LBD (r = + 0.854), yet, an inverted relationship was not seen between total cholesterol and LAD (r = -0.315) nor between total cholesterol and serum albumin (r = -0.248). PMID- 1910558 TI - [Neuroblastoma in Costa Rica: the experience with 76 cases treated at the Hospital Nacional de Ninos]. AB - Between 1970 an 1988, 76 patients with neuroblastoma (39 males and 37 females) were treated at the National Children's Hospital. The children's ages ranged from 1 month to 10 years. The location of the neuroblastoma was retroperitoneal in 71% of the cases, mediastinal in 20%, in either the head or neck 4% and unknown in 5%. Twelve percent were classified as E I-II, 35% in E III, 50% in E IV and 3% in E IVS. Seventy-seven percent of the cases died and the remaining 33% are in remission, with a follow-up of 12 to 220 months. Fifty of the cases were histologically reclassified according to Shimada. Survival rates were correlated with age, histology, E classification and treatment, in order to establish prognostic factors in relation to the disease: children under 24 months have a survival rate of 43%, statistically greater than in those children older who have an 8% survival rate. Shimada's classification is useful in predicting the child's survival when under 18 months of age and with tumors with a low ICM (81% survival) and a high ICM (6%). Patients classified as E I-II have a survival rate of 74%, those in E III-38% and in E IV-4%. In relation to the chemotherapy, a ten year survival is thought to be 14% for the 22 cases in E III and IV who were given medication and 21% for the other 36 who were given three drugs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1910559 TI - [Auditory brain stem evoked potentials of average latency in dyslexics and controls]. AB - The goal of this paper was to study the auditory pathway of nine controls and nine pure dyslexic subjects using brainstem auditory evoked responses and middle latency responses. We found no differences in latency and amplitude between both groups; only a small difference in the V right/V left relation in favour of the right V wave in controls and left V wave in dyslexics. This findings is discussed in relation to cerebral dominance. PMID- 1910560 TI - [The neuroevolutionary profile of the nursing infant with macrocephaly and benign enlargement of the subarachnoid space]. AB - With the purpose of studying the neuroevolutionary prognosis of children with macrocephaly (percentile 95) and the widening of the subarachnoid space, identified using head CAT scans-five cases were selected from the Pediatric Neurology Department from the Teaching Regional Hospital of Trujillo-Peru, seen during January 1983 and January 1988 with a follow-up of 1 and 1/2 and 3 years. All of the children showed an abnormal separation of the frontal subarachnoid space, interhemispheric fissure and Silvio incision without ventriculomegaly o a minimal dilation of the ventricular system. Through neurological evaluation and the Denver Development Test, in all cases except one, a characteristic pattern of hypotony and gross motor retardation were seen during the first year of life, which was modified towards normality during the following months until the age of 24 to 40 months. This findings suggest the good prognosis and benign nature of this condition which can be spontaneously resolved and apparently related to benign family macrocephaly. PMID- 1910561 TI - [Pancreatic pseudocyst. A case report and review of the literature]. AB - This is the case of a 15 year old adolescent girl who refers recurrent chronic abdominal pain for a period of three months. She was diagnosed as having a chronic pancreatic pseudocyst, seen as a complication of an episode of hemorrhage acute pancreatitis secondary to the administration of L-asparaginase for the treatment of acute lymphoblastic leukemia. The abdominal ultrasonography allowed for a pre-operatory diagnosis to be made. An internal drainage and a cystogastrostomy were the procedures of choice. A review of the literature is included on the physiopathology, clinical history, diagnostic procedures and therapeutic conduct to be followed. PMID- 1910562 TI - [In memoriam Prof. Ciriaco Laguna]. PMID- 1910563 TI - Grating acuity of cats measured with detection and discrimination tasks. AB - In order to help resolve the widely discrepant claims for the grating acuity of the cat, behavioral measurements were made of the acuities of two normal adult cats using two different tasks. In one, a conventional detection task, the cats were required to discriminate between high contrast vertical gratings and a uniform field of the same space-averaged luminance. The second, less commonly used task, required the cats to discriminate between vertical and horizontal gratings of the same spatial frequency. Both cats obtained thresholds of between 8.5 and 9 cycles/degree, with no difference between tasks. These results suggest that detection of aliased patterns is not a likely factor contributing to the wide range of published acuities, and they provide support for one of two competing models of beta-ganglion cell sampling in the retina. PMID- 1910564 TI - Localized brain metabolic response correlated with potentials evoked by words. AB - Evoked potentials (EPs) measure synaptic current flows that propagate from brain to scalp, Alternatively, positron emission tomography (PET) using fluoro deoxyglucose (FDG) can measure the increased glucose metabolism supporting this synaptic activation. It is difficult to localize the brain activity-generating EPs from their scalp distribution, because activity originating in different regions tends to produce overlapping scalp topographies. In contrast, FDG-PET provides better spatial resolution for activity throughout the brain, but shows only the total metabolism integrated over a 30-min uptake period. We combined the temporal and psychological resolution of EPs with the spatial resolution of PET to help define when and where in the brain words are encoded for meaning. PMID- 1910565 TI - Effects of water temperature and core temperature on rat's performance in a swim to-platform test. AB - Hypothermic rats are grossly deficient in acquisition in a simple swim-to platform task if the core temperature is 28-30 degrees C or lower. However, the ability to swim is relatively well preserved. Normothermic rats perform slightly better in cold water than in warm water. PMID- 1910566 TI - Morphine effects in brainstem-transected cats: I. EEG and 'sleep-wakefulness' in the isolated forebrain. AB - In order to examine the prosencephalic mechanisms that might sustain the effects of opiates on EEG and sleep-wakefulness, the actions of morphine sulfate on the EEG and the pupil size were examined in the chronically isolated forebrain of brainstem-transected cats. Single morphine doses (0.5, 2.0 or 3.0 mg/kg, i.p.) administered to these animals produced a long-lasting EEG desynchronization in the isolated forebrain which was associated with pupil mydriasis. The specificity of these morphine effects was shown by the fact that naloxone blocks both the EEG and pupillary effects of the drug. After morphine, spontaneous synchronized EEG with delta waves normally seen in the isolated forebrain preparation was suppressed for 6-18 h, followed by a strong rebound. Both the suppression and rebound in synchronization with delta waves occurred in a dose-dependent manner. The duration of these effects closely paralleled previously reported morphine effects on non-rapid eye movement (NREM) sleep in intact cats. Therefore, in relation to the effects of morphine on EEG and sleep-wakefulness in intact animals, this study suggests that: (1) Morphine suppression of NREM sleep and the subsequent arousal state of the animal are mediated by prosencephalic structures; (2) the generation of the typical neocortical EEG slow burst activity produced by opiates depends on lower brainstem structures. PMID- 1910567 TI - Morphine effects in brainstem-transected cats: II. Behavior and sleep of the decerebrate cat. AB - Previous studies have shown that opiates suppress both non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. Furthermore, during the induced insomnia period, characteristic species-specific behaviors occur which are associated with high voltage slow waves in the EEG. This paper investigates the lower brainstem mechanisms involved in the generation of these effects, and describes the action of single morphine doses (0.5, 2.0 or 3.0 mg/kg, i.p.) on the behavior and REM sleep of chronic decerebrate cats. The effects of morphine in the decerebrate cat followed a 3-stage time course similar to that seen in intact cats: (1) autonomic manifestations (3-8 min postdrug); (2) a quiet state (10-60 min postdrug) with behavioral signs of NREM; and (3) a state of activated behavior (1-6 h postdrug), including motor activity and variations in muscle tone. The decerebrate cats also showed a dose-dependent suppression of REM sleep. The present results indicate that: (1) the lower brainstem provides the basic mechanisms for the behavioral deactivation-activation and the autonomic effects of the drug; (2) hypnogenic and synchronizing influences arising from the brainstem might induce the high voltage, slow burst EEG produced by opiates; (3) REM sleep suppression originates only partially in the lower brainstem; (4) the subsidiary action of the prosencephalon seems to be required for the full expression of the drug's effect on behavior and the EEG. PMID- 1910569 TI - Three-dimensional trajectories of the hippocampal rhythmic slow activity in the behaving rat. AB - Movement-concurrent rhythmic slow activity (RSA) was recorded by means of 3 pairs of bipolar electrodes which were arranged so that they orthogonally encompassed the dorsal hippocampus in the freely moving rat. The 3-channel data were combined by synchronously plotting them on independent voltage axes and the resultant 3 channel Lissajous' trajectory (3-CLT) was depicted in 3-dimensional microcomputer processing. A type of 3-CLT which traversed the surface of an ellipsoid with the long axis nearly perpendicular to the medial CA1 pyramidal layer, appeared most abundantly during walking. A 3-CLT depicting curves on a spherical surface was frequently produced during sitting. A linear 3-CLT of short duration was occasionally produced during rearing. These findings suggest that alteration of voltage axis specific to a behavior is possibly generated associating with the hippocampal RSA. PMID- 1910568 TI - Are eyeblink responses to tone in the decerebrate, decerebellate rabbit conditioned responses? AB - Bloedel and associates recently claimed to have established conditioned eyeblink responses in the acute decerebrate, decerebellate rabbit. Their training procedure was extreme massed practice (mean intertrial interval of 9 s) and they used an idiosyncratic definition of the conditioned response (10% or more of the unconditioned response amplitude). They did not measure or control the excitability of their preparations and did not run any separate control groups for alpha responses, alpha conditioning or pseudoconditioning. Using normal animals we compared their training procedure with procedures standard in the field and analyzed the consequences of their scoring procedure. Our group trained at a 30-s intertrial interval (ITI) showed clear learning in the training session. In marked contrast, 3 groups trained at a 9-s ITI developed no conditioned responses. We also found that the method of scoring used by Bloedel and associates counts many spontaneous responses as conditioned responses (CRs) if unconditioned response (UR) amplitudes are low, excludes genuine CRs if UR amplitudes are high and does not control for the occurrence of spontaneous responses. It must therefore be concluded that the eyeblink responses to tone reported by Bloedel and associates to occur in the decerebrate, decerebellate rabbit are not associative CRs as they develop in the normal animal. PMID- 1910570 TI - Perinatal flutamide and mounting and lordosis behavior in adult female Wistar and Sprague-Dawley rats. AB - The present study was designed to investigate the possible role of perinatal androgens acting via the androgen receptor, as opposed to the estrogen receptor, for the differentiation of adult mounting and lordosis behavior in female rats. Female Wistar (W) and Sprague-Dawley (SD) rats were exposed to the anti-androgen flutamide prenatally (days 11-22 of pregnancy) and/or neonatally (days 1-10). The females were ovariectomized in adulthood and repeatedly tested for mounting and lordosis behavior. Flutamide, given both pre- and neonatally to SD rats, reduced adult T-induced female mounting. Flutamide administered only prenatally or only neonatally did not lower adult mounting behavior of SD rats. Mounting behavior of female W rats, following pre- and/or neonatal flutamide treatment was not affected. Lordosis behavior was also not altered by perinatal flutamide treatment of either strain. The results of the present study, no effect of prenatal flutamide, do not support the hypothesis that female rats require prenatal androgen receptor-mediated actions of testosterone in the organization of neural tissues for the occurrence of adult mounting and lordosis behavior. Only in SD rats androgenic organization of adult mounting behavior via the androgen receptor seems to occur both pre- and neonatally. Since clear behavioral effects of prenatal flutamide treatment have been published earlier in Long-Evans females, we suggest strain differences in sensitivity for perinatal androgenization in female rats. Future research into that possibility is needed. PMID- 1910571 TI - Effects of short-lasting inactivations of the ventral hippocampus and medial septum on long-term and short-term acquisition of spatial information in rats. AB - This study was aimed at testing the effects of a reversible inactivation of the hippocampal formation on long-term and short-term acquisition of spatial information. Rats chronically equipped with either bilateral cannulae into the ventral hippocampus or a single cannula into the medial septum had to locate, in a circular platform with 18 holes on the periphery, the unique hole leading to a hidden shelter in order to avoid bright light. In Expt. 1, following 16 days of training (1 trial/day, 24 h ITI) without physical intervention, the location of the correct hole was changed on both Days 17 and 23, and the rats were either sham-injected or injected with lidocaine. Both hippocampally and septally lidocaine-injected rats relearned the new location at a rate similar to corresponding sham-injected animals. In Expt. 2, a massed-trial version of the task was used, in which the rats had to learn a new hole location on each daily session (3 trials, ITI = 1 min). Animals were sham-injected or lidocaine-injected on alternate sessions. While sham-injected rats improved in orientational accuracy over successive trials, both hippocampally and septally lidocaine injected rats failed to display any between-trial improvement. The impairment displayed by lidocaine-injected rats when their hippocampus was inactivated confirms the role of the hippocampus in short-term spatial memory (Expt. 2). In contrast, short-lasting inactivation of the hippocampus did not prevent long-term spatial learning (Expt. 1). These results suggest that the hippocampus could process information 'off-line' in the delay between temporally discontiguous learning trials, and show that short-term and long-term spatial learning rely on distinct neurobiological mechanisms. PMID- 1910572 TI - Spatial problem-solving in a wheel-shaped maze: quantitative and qualitative analyses of the behavioural changes following damage to the hippocampus in the rat. AB - The behaviour of sham-operated rats and rats with damage to the dorsal hippocampus was compared in a complex spatial problem-solving task using a 'hub spoke-rim' wheel type maze. Compared to the classical Olton 8-arm radial maze and Morris water maze, this apparatus presents the animal with a series of possible alternative routes both direct and indirect to the goal (food). The task included 3 main stages: exploration, feeding and testing, as do the classic problem solving tasks. During exploration, hippocampal rats were found to be more active than sham rats. Nevertheless, they displayed habituation and a relatively efficient circumnavigation, though, in both cases, different from those of sham rats. During test trials, hippocampal rats were characterized as being less accurate, making more errors than sham rats. Nevertheless, both groups increased their accuracy of first choices over trials. The qualitative analyses of test trial performance indicated that hippocampal rats were less accurate in terms of the initial error's deviation from the goal, and less efficient in terms of corrective behaviour than sham rats which used either the periphery or the spokes to attain economically the goal. Surprisingly, hippocampal rats were not limited to a taxon type orientation but learned to use the periphery, a tendency which developed over time. Seemingly, for sham rats, the problem-solving process took the form of updating information during transit. For hippocampal rats, the use of periphery reflected both an ability to discriminate its usefulness in reaching the goal via a taxis type behaviour, and some sparing of ability to generalize the closeness and the location of the goal. These results, especially the strategic correction patterns, are discussed in the light of Sutherland and Rudy's 'configurational association theory'. PMID- 1910573 TI - Effects of prenatal ethanol exposure on learned persistence and hippocampal neuroanatomy in infant, weanling and adult rats. AB - The present experiment examined whether deficits in learned persistence, previously seen in 15-day-old infant rats prenatally exposed to ethanol, would be present in weanling and adult animals. Three prenatal treatments, EtOH, PAIR-FED, and LAB CHOW, were combined factorially with partial (PRF) or continuous (CRF) reinforcement training followed by extinction, at 21 days or 6 months of age. The results at 21 days were virtually the same as our earlier findings for 15-day olds: we did not find the higher level of persistence in PRF-trained EtOH pups relative to CRF-trained EtOH pups, which characterizes the partial reinforcement extinction effect (PREE). The EtOH-PRF and EtOH-CRF animals extinguished at about the same rate, both faster than PRF controls. However, when tested as adults, the EtOH-exposed animals showed a normal PREE, with no deficits relative to controls. An analysis of CA1 pyramidal cells in midtemporal hippocampus demonstrated no significant differences in cell density or in CA1 area among the 3 prenatal diet conditions; however, there was a significant reduction in cell density with age for all groups. These results suggest that a developmental delay, unrelated to these neuroanatomical measures, is responsible for the lack of persistence in young rats exposed prenatally to ethanol. PMID- 1910574 TI - Vibrissa-related behavior in mice: transient effect of ablation of the barrel cortex. AB - Knowing that the mystacial vibrissae are an important part of the tactile sensory apparatus of rodents, we investigated the role of the barrel cortex - the endstation of the pathway between whiskerpad and cerebral cortex - in mouse behavior. We tested 15 female adult mice 2 and 10 weeks after both unilateral ablation of the barrel cortex and removal of the vibrissae on the same side in order to assess acute as well as transient effects of the cortical lesion. Two kinds of behavioral tests were performed on animals permanently provided with opaque lenses: one involved a passive stimulation of the vibrissae; the other was the 'gap-crossing' test which required the animal's active use of the vibrissae. Lesioned subjects did not show a deficit during passive stimulation of the vibrissae. On the contrary, there was a deficit during the gap-crossing test 2 weeks after the ablation of the barrel cortex. The deficit partly disappeared when the subjects were tested 10 weeks later. The results show that in mice, the barrel cortex is involved in the performance of complex behavioral tasks. The recovery of function could be due to changes in strategies to solve the gap crossing test and/or to physical changes in neuronal circuitry. In either case, the results are relevant for the interpretation of cortical transplantation models using the whisker-to-barrel pathway. PMID- 1910575 TI - Glucosidase II from control and ethanol-treated rats. Purification and properties. AB - Liver glucosidase II from control and ethanol-treated rats was purified and its physical and catalytic properties studied. No significant variation was found in the purification and properties of the enzyme from either source (ethanol-treated and control rats), except for activity after storage. Glucosidase II was purified to electrophoretic homogeneity from liver microsomes by solubilization, protamine sulphate precipitation, and anion exchange (DEAE-Sephacel) and affinity (Con A Sepharose-4B) chromatographies. The native enzyme molecule is a tetramer (Mr 425 +/- 10 kDa) with identical subunits (Mr 106 +/- 3 kDa). Km values, determined at pH 6.8 for the p-nitrophenyl-glucosidase activity of glucosidase II from control and ethanol-treated rats, were 1.20 +/- 0.12 and 1.14 +/- 0.13 mM, respectively. The Arrhenius plot was linear, and the value for the apparent activation energy, calculated from this plot, was 56.64 kJ/mol. The p-nitrophenyl-glucosidase activity of glucosidase II from control and ethanol-treated rats was inhibited to the same extent by NH4+, by the divalent cations Ca2+ and Mg2+, and by methanol, ethanol, 2-propanol, n-propanol, isobutanol and n-butanol. PMID- 1910576 TI - Microbial metabolism of quinoline and related compounds. IX. Degradation of 6 hydroxyquinoline and quinoline by Pseudomonas diminuta 31/1 Fa1 and Bacillus circulans 31/2 A1. AB - Two strains, using 6-hydroxyquinoline as sole source of energy, carbon and nitrogen, have been isolated. These bacteria, designated 31/1 Fa1 and 31/2 A1, are also able to degrade quinoline. According to their physiological properties strain 31/1 Fa1 has been identified as Pseudomonas diminuta and strain 31/2 A1 as Bacillus circulans. 6-Hydroxy-2-oxo-1,2-dihydroquinoline was found as intermediate in the degradation of 6-hydroxyquinoline and quinoline. 2-Oxo-1,2 dihydroquinoline was the first metabolite in the degradation of quinoline. PMID- 1910577 TI - Kinetics of nitroanilide cleavage by astacin. AB - The investigation of the catalytic properties of astacin, a zinc-endopeptidase from the crayfish Astacus astacus L., has gained importance, because the enzyme represents a novel, structurally distinct family of metalloproteinases which also includes a human bone morphogenetic protein (BMP1). Astacin releases nitroaniline from succinyl-alanyl-alanyl-alanyl-4-nitroanilide (Suc-Ala-Ala-Ala-pNA), a substrate originally designed for pancreatic elastase. This activity was unexpected since only few metalloproteinases cleave small nitroanilide substrates, and, moreover, the primary specificity of astacin toward protein substrates is determined by short, uncharged amino-acid sidechains in the P'1 position, i.e. the new N-terminus after cleavage. The specificity constants, kcat/Km, for the release of nitroaniline from substrates of the general structure Suc-Alan-pNA (n = 2, 3, 5) and Alan-pNA (n = 1, 2, 3) increase with the number of alanine residues. The longest peptide, Suc-Ala(-)-Ala-Ala-Ala-Ala-pNA, is the only one out of eleven substrates used in this study, which is cleaved at two positions by astacin. The first cleavage yields Suc-Ala(-)-Ala and Ala-Ala-Ala pNA. From the resulting C-terminal fragment, Ala-Ala-Ala-pNA, a second cut releases nitroaniline. The 1200-fold higher specificity constant observed for the first as compared to the second cleavage in Suc-Ala-Ala-Ala-Ala-Ala-pNA reflects the preference of astacin for true peptide bonds and also the importance of a minimum length of the substrate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1910578 TI - The primary structure of the hemoglobin from the aardwolf (Proteles cristatus, Hyaenidae). AB - The hemoglobin of the aardwolf (Proteles cristatus) contains only one component. In this paper, we are presenting its primary structure. The globin chains were separated by high-performance liquid chromatography and the sequences determined by automatic liquid and gas-phase Edman degradation of the chains and their tryptic peptides. The alpha- as well as the beta-chains show 20 exchanges compared with the corresponding human chains. The difference to the masked palm civet (Paguma larvata) and the spotted hyaena (Crocuta crocuta) is marked by 16 and 4 replacements in the alpha-chains and by 10 and 1 in the beta-chains, thus supporting the hyaenid character of the aardwolf. The exchanges at contact positions are shared by other carnivoran hemoglobins. PMID- 1910579 TI - A non-invasive technique for cell volume determination in perfused rat liver. AB - 1) In isolated perfused rat liver, the intracellular ([14C]urea-accessible minus [3H]inulin accessible) water space was determined from the washout profiles of simultaneously infused [3H]inulin and [14C]urea. The washout profile of infused [14C]urea was indistinguishable from that of infused tritiated water. During normotonic perfusions and without hormones or amino acids in influent, the intracellular water space was 548 +/- 10 microliters/g liver wet weight (n = 44). Use of [3H]raffinose instead of [3H]inulin as marker for the extracellular space yielded almost identical values for the intracellular water space (i.e. 98.9 +/- 0.2% of that found with [3H]inulin/[14C]urea). When volume-regulatory K+ fluxes were completed following hypo- and hypertonic exposure of perfused rat livers and a steady state was reached, the intracellular water space was found to be increased and decreased, respectively. The extent of anisotonic exposure was linearly related to the change of intracellular water space. 2) Anisotonicity-, glutamine- and glycine-induced liver mass changes were almost fully explained by the simultaneously occurring alterations of the intracellular water space, indicating that cell volume changes in perfused rat liver under these conditions are not accompanied by significant changes of the extracellular space. Volume regulatory K+ (plus accompanying anion) efflux following hypotonic perfusion accounted for about 70-85% of regulatory cell volume decrease, which occurred during the first 10 min of hypotonic exposure. 3) Cell volume of isolated hepatocytes was determined as the "hepatocrit" after gentle centrifugation of the cell suspension.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1910580 TI - Release of dog polymorphonuclear leukocyte cathepsin G, normally and in endotoxin and pancreatitic shock. Isolation and partial characterization of dog polymorphonuclear leukocyte cathepsin G. AB - Dog polymorphonuclear leukocyte cathepsin G was isolated from a granule extract using a two-step procedure including affinity chromatography on a Trasylol Sepharose gel and ion-exchange chromatography on a CM 52 column. 22 of the first 24 N-terminal amino acids were determined and showed 83% and 71% identity to those of human and rat cathepsin G, respectively. Total amino-acid composition demonstrated the basic nature of the protein. In an SDS/polyacrylamide-gel electrophoresis the protein showed an Mr of 29,400 compared to the Mr of 26,800 calculated from the total amino-acid composition. The enzyme was shown to form complexes with alpha 1 alpha 2-macroglobulin and alpha 1-proteinase inhibitor. A specific enzyme-linked immunosorbent assay was developed for the determination of cathepsin G/alpha 1-proteinase inhibitor complex in dog plasma and tissue fluids. The mean concentration of cathepsin G in normal dog plasma was determined to be 38 micrograms/l, measured as cathepsin G/alpha 1-proteinase inhibitor complex. When active dog cathepsin G was added to normal dog plasma in vitro, approximately 56% could be measured by the assay. Slow intravenous infusion of a lethal dose of endotoxin in dogs was followed by a marked drop in white blood cell count and thrombocytes and a simultaneous rapid increase in plasma cathepsin G concentration, reaching a maximum level of 150 micrograms/l. Bile-induced experimental pancreatitis in dogs was accompanied by successive increase in cathepsin G levels in plasma as well as in peritoneal exudates, reaching a maximum level of about 300 micrograms/l in plasma and 18 mg/l in the exudates during the late stages of disease. PMID- 1910581 TI - Sialidase in the guinea pig pulmonary parenchyma. Increased activity in the cytosolic and microsomal subcellular fractions after stimulation with Bacillus Calmette Guerin. AB - The sialidase activity was assayed in the guinea pig pulmonary parenchyma after removal of bronchoalveolar cells by washing. After differential centrifugation of the crude tissue homogenate, sialidase activities were measured in the subcellular fractions using the fluorogenic substrate 2-(4-methylumbelliferyl) alpha-D-N-acetylneuraminate. Sialidase activities were found in the lysosomal enriched (17,000 x g pellet), in the microsomal (105,000 x g pellet) and in the cytosolic (105,000 x g supernatant) fractions. Microsomal and lysosomal forms of sialidase had an optimum activity at pH 3.6-3.8, whereas the optimum for the cytosolic form was pH 4.6. The activity of all three forms was inhibited by Cu2+, whereas 1 mM Zn2+ and 0.5 mM Ca2+ activated the lysosomal and the cytosolic forms, respectively. In the crude homogenate taken from lungs of Bacillus Calmette Guerin-(BCG-) stimulated guinea pigs, the sialidase activity was increased by 43% (p = 0.025) 3 weeks after the end of the treatment. The cytosolic (+246%) and microsomal (+51%) sialidase activities were significantly increased, whereas the lysosomal sialidase activity was not changed significantly by BCG stimulation. PMID- 1910582 TI - Lysosomal and plasma membrane ganglioside GM3 sialidases of cultured human fibroblasts. Differentiation by detergents and inhibitors. AB - Cultured human fibroblasts contain two sialidases that degrade gangliosides such as GM3: a lysosomal activity that appears identical with the activity towards water-soluble substrates and that is deficient in the genetic lysosomal disorder sialidosis, and another enzyme that seems localized on the external surface of the plasma membrane. In this report we show that both enzymes can be differentiated in the presence of each other by choice of the detergent used for activation, and also by the inhibitory action of some polyanionic compounds such as sulphated glycosaminoglycans. The lysosomal ganglioside GM3 sialidase is greatly stimulated by sodium glycodeoxycholate and, to lesser degrees, by sodium glycocholate and sodium cholate. The ganglioside GM3 sialidase of the plasma membrane is not measurably active under the conditions of the lysosomal enzyme but is specifically activated by the non-ionic detergent Triton X-100. The glycodeoxycholate-stimulated, but not the Triton-activated, ganglioside GM3 sialidase activity was profoundly diminished in cell lines from patients with the lysosomal disorders sialidosis and galactosialidosis; however, both activities were normal in fibroblasts from patients with mucolipidosis IV, previously thought to be a ganglioside sialidase deficiency disorder. Both the lysosomal and the plasma membrane ganglioside GM3 sialidases were inhibited by sialic acids, suramin, dextran sulphate and sulphated glycosaminoglycans. Among the latter, heparin and heparan sulphate showed a much higher inhibitory potency towards the plasma membrane ganglioside GM3 sialidase than towards the lysosomal onw.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1910583 TI - Primary structure of the murine monoclonal IgG2a antibody mAb735 against alpha(2 8) polysialic acid. 1) Amino-acid sequence of the light (L-) chain, kappa isotype. AB - Here we report the complete amino-acid sequence of the anti-alpha(2-8)polysialic acid antibody mAb735 light chain. The sequence was determined after digestion of the reduced and carboxymethylated L-chain with trypsin, SV-8 proteinase, and Asp N proteinase, isolation of the generated peptides by RP-HPLC and characterization of these fragments by sequence analysis, amino-acid analysis and/or plasma desorption mass spectrometry. According to Kabat et al. the variable region belongs to the V kappa-II subgroup, whilst according to Hum et al. it belongs to the V kappa-1B subgroup. With the exception of proline at position 46, the sequence from position 1 to 95 is identical to the translated DNA sequence of a V kappa-germline gene segment previously reported. PMID- 1910584 TI - Factors influencing the stability of heme and ferrochelatase: role of oxygen. AB - Ferrochelatase (EC 4.99.1.1) catalyzed heme synthesis is best accomplished in an anaerobic environment. Factors responsible for this phenomenon are not fully understood. Oxygen sensitivity of this reaction may be due to (a) oxidation of essential thiol groups on the enzyme, (b) oxidation of ferrous ions, or (c) the formation of hydrogen peroxide. These possibilities were investigated using rat liver ferrochelatase preparations and a continuous, dual-wavelength assay. Dithiothreitol and ascorbic acid stimulated the ferrochelatase reaction whereas GSH was not as effective. Addition of GSSG had little influence on the enzyme reaction. Total ferrochelatase activity in the assay remained unaffected at the end of the incubation and inclusion of glutathione peroxidase did not alter these results. Thus, ferrochelatase itself was not inactivated by oxidation. In selenium-deficient rats, the mitochondrial ferrochelatase levels were maintained even when glutathione peroxidase activity was significantly depleted. However, glutathione peroxidase very effectively inhibited the thiol-dependent aerobic degradation of heme. These results suggested that autoxidation of heme and of ferrous ions to the unusable ferric form largely contribute toward the oxygen sensitivity of the ferrochelatase reaction in vitro. PMID- 1910585 TI - Human red blood cells as bioreactors for the inactivation of harmful xenobiotics. AB - Human red blood cells are able to inactivate lipophilic electrophiles by conjugation with reduced glutathione. This metabolic ability was found to be limited by the rate of permeation of the xenobiotic into erythrocytes and by the amount of available reduced glutathione. By a procedure of hypotonic dialysis, isotonic resealing and reannealing human red blood cells were overloaded with increasing amounts of reduced glutathione up to three- to fourfold the normal level without modification of their metabolic functions or of their energetic state. These overloaded erythrocytes were able to conjugate increasing amounts of xenobiotics and to export the resulting conjugates from the cells. These properties of glutathione overloaded erythrocytes are significant for the use of carrier erythrocytes in cases of acute intoxication by lipophilic electrophiles. PMID- 1910586 TI - Efficient production of recombinant DNA proteins in Saccharomyces cerevisiae by controlled high-cell-density fermentation. AB - High levels of expression of heterologous proteins (from 5 to 15% of total cell proteins) in the budding yeast Saccharomyces cerevisiae have been obtained previously by the use of the inducible strong hybrid promoter UASGAL/CYC1, in batch as well in continuous cultures. However, in order to maximize the yield of heterologous proteins, a computer controlled fed-batch fermentation is essential. For this reason we have developed a fed-batch system based on a semiconductor gas detector that measures ethanol in the outflow gases. The optimal conditions are described for very high production (up to 1550 mg/liter), with both high productivity (up to 100-120 mg/liter/h) and high yield (up to 15 mg of protein/g of dry biomass), of heterologous protein driven by the UASGAL/CYC1 promoter in a completely computer controlled fed-batch fermentation of budding yeast. However, high production was dependent upon the addition of a large amount of galactose. The process was improved by developing a new, more easily inducible, vector system obtained by subcloning the GAL4 gene. PMID- 1910587 TI - Recent advances in biomarker research. PMID- 1910588 TI - Carcinogen-macromolecular adducts as biomarkers in human cancer risk assessment. AB - Substantial data have been generated during the past 5 years in both experimental systems and human populations which shed light on the potential role of carcinogen-macromolecular adducts in human cancer risk assessment. The use of DNA and protein adducts is based on the fundamental concept in chemical carcinogenesis that most genotoxins are metabolized to electrophilic "ultimate" carcinogens that are capable of forming covalent adducts with cellular macromolecules. This report examines the relative usefulness and limitations of using DNA and protein adducts and related techniques for assessing human exposure to genotoxic carcinogens. Data discussed in this report clearly demonstrate that these biomarkers not only allow early detection of potential cancer hazard in humans, but they can also significantly increase the power of conventional cancer epidemiological studies in determining true causal relationships. In addition, such biomarkers can improve extrapolation of cancer risks from laboratory animals to humans or from one human population to another. PMID- 1910589 TI - Critical considerations in the immunochemical detection and quantitation of antigenic biomarkers. AB - The formation of covalent adducts as a result of the interaction of metabolically activated chemicals with host macromolecules is a common critical event in mutagenic, carcinogenic, and immunologic phenomena. Because of their antigenicity and their immunogenicity, covalent adducts may be detected using sensitive immunochemical techniques. The immunochemical approaches to biomonitoring and molecular dosimetry of DNA damage are particularly attractive because they allow sensitive quantitation of specific DNA adducts present in small samples and do not rely on the use of radiolabeled adducts. Two examples of biomarker immunoassay development are presented: an avidin/biotin-amplified ELISA for the major DNA adduct of the human bladder carcinogen 4-aminobiphenyl (ABP), and a particle concentration fluorescent immunoassay (PCFIA) for the major protein adduct associated with toxicity by the prototype hepatotoxin acetaminophen. The examples illustrate critical steps in the development of biomarker immunoassays which include selection of the relevant adduct, preparation of an appropriate immunogen, immunization, characterization of antisera, and development of application-specific sample processing techniques for biomarker quantitation. Immunochemical procedures may be combined with other analytical techniques to form hybrid systems which take advantage of both the antigenicity and the physical or chemical properties of a biomarker to achieve greater specificity and/or sensitivity. The future usefulness of these new tools of molecular epidemiology will depend on a compound-by-compound validation of methods and critical evaluation of the biologic importance of the particular antigenic biomarker as an indicator of exposure and as an indicator of risk. PMID- 1910590 TI - Biomarkers of aging: an overview. PMID- 1910591 TI - The effects of dietary restriction and aging on in vivo and in vitro binding of aflatoxin B1 to cellular DNA. AB - Laboratory animals maintained on a reduced calorie but nutritionally adequate diet have extended life spans and lowered incidences of spontaneous and chemically induced cancers compared to ad libitum- fed counterparts. Many of the effects of dietary restriction on laboratory animals have been suggested to be related to a deceleration of the aging process. The inhibition of age-related changes in xenobiotic metabolizing enzymes activities by dietary restriction has previously been reported. Alterations of these enzyme activities may cause changes in metabolic activation of carcinogens and, therefore, carcinogen-DNA binding. DNA-repair capability has also been reported to be enhanced in diet restricted rats. Using AFB1 as a model carcinogen, we have studied in vivo and in vitro hepatic AFB1-DNA binding, demonstrating that dietary restriction (60% of ad libitum consumption) may decrease the metabolic activation of AFB1, and subsequently reduce AFB1-DNA binding. Our preliminary results obtained from the AFB1-DNA binding experiments in isolated hepatocytes suggest that the observed age-dependent reduction in AFB1-DNA binding which may be attributed to a loss of metabolic activating capability was delayed in the diet-restricted rats. PMID- 1910592 TI - Neurobehavioral biomarkers of aging: influence of genotype and dietary restriction. AB - Because of the importance of central nervous system (CNS) functions to productive capacity and quality of life, biomarkers of these functions will play a key role in evaluating the success of interventions targeting aging processes. The CNS biomarkers may also be useful for predicting aging in other systems and in the organism as a whole. Age-related behavioral changes, the products of CNS aging, have content and predictive validity with respect to human functional capacities and may, therefore, represent important "neurobehavioral" markers of functional aging. This article presents a discussion of some behavioral paradigms which are currently being considered as neurobehavioral biomarkers of aging in mice and the experimental approaches being employed in the assessment of their validity. Studies conducted in the authors' laboratory using dietary restriction and genetic comparisons to evaluate the validity of neurobehavioral biomarkers have revealed several methodological concerns, and hypothetical and empirical examples of these pitfalls are described and discussed. In spite of those concerns, it is concluded that approaches to validity using genetic comparisons and dietary restriction can be successfully implemented and should ultimately lead to identification of valid and useful neurobehavioral biomarkers of aging. PMID- 1910593 TI - Individual differences in aging: behavioral and neural analyses. AB - Aged populations have remarkable variability in recent memory and cognitive mapping. Although some individuals may have substantial age-related impairments, others perform almost as well as young individuals. This paper reviews the relevant data on aged rats and indicates two challenges for biomarkers of aging. The first is to provide an appropriate quantitative description of these individual differences. The second is to use them effectively as markers for age related changes in psychological functions and their neural substrates. PMID- 1910594 TI - Biomarkers of aging: changes in circadian rhythms related to the modulation of metabolic output. AB - Twenty-four hour (circadian) rhythmicity is an important component of biological variability associated with studies relating to biomarkers of aging. Chronobiological testing techniques must be utilized because (1) many variables that are related to the modulation of metabolic output vary dramatically at different times of the day; (2) various experimental variable and treatment groups must be synchronized with environmental cues that control circadian rhythms; and (3) multiple circadian variables may interact together to modulate the rate of aging. The rhythm for physiological factors such as whole animal metabolic output, body temperature, heart rate, urine flow, potassium, etc. were found to be dissociated or altered by the senescence process; behavioral variables such as spontaneous activity, wheel running, feeding and drinking, verbal performance, as well as sleep-wakefulness rhythms, seem to be accurate predictors of biological age. Circadian rhythms for a variety of enzymes of intermediary metabolism which are directly associated with energy metabolism have been well documented. These well-defined rhythms of enzyme activity have also been shown to degenerate with aging. Rhythms tend to lose amplitude as activity falls with age and as a general loss of regulation (especially time of day where maximal activity might be found) of activity across the 24-h span occurs. As with behavioral variables, changes in enzyme rhythms appear to accurately predict aging. Generally speaking, the loss of temporal organization with age, characterized by decreased circadian amplitude, loose internal synchronization, and poor response to external environmental time queues, is associated with poor health states and decreased longevity. Temporal rhythms for whole animal parameters are highly correlated with molecular events, such as regulation of cellular metabolism. DNA repair, and gene expression. Automated data acquisition and process control systems will be required for future chronobiological studies to develop biomarkers of aging. PMID- 1910595 TI - Biomarkers of neurotoxicity: an overview. PMID- 1910596 TI - Assessment of neurotoxicity: use of glial fibrillary acidic protein as a biomarker. AB - Diverse neurotoxic insults result in proliferation and hypertrophy of astrocytes. The hallmark of this response is enhanced expression of the major intermediate filament protein of astrocytes, glial fibrillary acidic protein (GFAP). These observations suggest that GFAP may be a useful biomarker of neurotoxicity. To investigate this possibility, we administered prototype neurotoxicants to experimental animals and assessed the effects of these agents on the tissue content of GFAP, as determined by radioimmunoassay. A review of the background, design, and results of these experiments are presented in this paper. Our findings indicate that GFAP is a sensitive and specific biomarker of neurotoxicity. PMID- 1910597 TI - Recent advances in biomarker research. Introduction. PMID- 1910598 TI - Oxygen radical generation as an index of neurotoxic damage. AB - Biochemical, anatomical, and physiological characteristics of the brain make it especially vulnerable to insult. Specifically, some of these characteristics such as myelin and a high energy requirement provide for the introduction of free radical-induced insult. Recently, the biochemistry of free radicals has received considerable attention. It also has become increasingly suggestive that many drug and chemical-induced toxicities may be evoked via free radicals and oxidative stress. Major points addressed in this work are the regulation of neural-free radical generation by antioxidants and protective enzymes, xenobiotic-induced disruption of cerebral redox status, and specific examples of neurotoxic agent induced alterations in free radicals as measured by the fluorescent probe dichlorofluorescein. This article considers that free radical mechanisms may contribute significantly to the properties of several diverse neurotoxic agents and proposes that free radicals may be common phenomena of neurotoxicity. PMID- 1910599 TI - Male reproductive toxicology. AB - The objective of this paper is to discuss recent developments in the application of biological markers to animal models of male reproductive toxicology. We have divided this paper into three major sections: First, a discussion of the testing protocols currently under investigation by the National Toxicology Program (NTP) and the EPA's Health Effects Research Laboratory; second, an examination of what we consider to be important and practical biological markers available to investigators to assess the effects of toxicants on the male reproductive system; and third, a discussion of promising new technologies, such as molecular and immunological probes, and in vitro techniques using isolated and cultured cells, which in the future may be exploited for the development of additional biological markers of male reproductive toxicity. Where appropriate we have made specific recommendations for the use of these biological markers in animal protocols and have pointed out those noninvasive markers which have application to screening human males. PMID- 1910600 TI - Laboratory models for the study of the peri-implantation period. AB - The greatest risks to mammalian pregnancy occur during the peri-implantation period (passage through the uterotubal junction, blastulation, zona shedding, embryonic signaling and recognition, blastocyst attachment, postattachment events initiating placentation). Conventional markers and screening methods do not provide the means to clarify the relationship between exposure of a reproductively competent woman to a xenobiotic compound and the specific error in the functional expression of an embryogenetic process identified by impairment or deletion of that process. Laboratory models which provide the flexibility of in vitro culture methods and allow integration of cellular and molecular techniques have identified cell-specific, stage-specific markers that could focus on the mechanism of xenobiotic action. In vitro models have been used to define postattachment trophoblast cell differentiation. Trophoblast specific peptide hormones prove to be valid markers of established pregnancy. They provide no assessment of the risk to the embryo during the peri-implantation period. The relationship between developmental time of exposure and risk is discussed in terms of trophoblast differentiation. PMID- 1910601 TI - Biological markers on human pregnancy. AB - This article reviews a selected set of recently described pregnancy-associated proteins which possess potential for both signaling pregnancy onset and monitoring its course. These molecules are compared and contrasted with human chorionic gonadotropin, the first pregnancy-associated protein to be discovered, and the standard biomarker of pregnancy to which all others must still be referenced. Recent advances in hCG research have focused on the structural determination and diagnostic significance of the subunits and fragments of the hCG molecule, particularly in urine. An outline of the potential utility of this approach is also presented. PMID- 1910602 TI - Biomarkers of human exposure to carcinogens: an overview. PMID- 1910603 TI - Biochemical and molecular epidemiology of cancer. AB - Examples of practical approaches to molecular epidemiology of human cancer are described. Biomarkers of carcinogen exposure or inherited host factors for cancer susceptibility are discussed. Major advances have been made in the detection of carcinogenmacromolecular adducts through the use of high performance liquid chromatography, immunoaffinity chromatography, the 32P-postlabeling assay, enzyme immunoassays, gas chromatography/mass spectroscopy and synchronous spectrophotofluorimetry. The polycyclic aromatic hydrocarbon-DNA adducts are the most extensively studied in this field and together with antibodies to these adducts found in human serum, they have become useful indicators of exposure to carcinogens. Assays for various kinds of alkyl-DNA adducts have also been developed and the presence of these adducts have been documented in human tissues. Carcinogen-protein adducts have proven to be useful molecular dosimeters of carcinogen exposure. For example, 4-aminobiphenyl hemoglobin adducts are highly correlated with exposure to tobacco smoke. The study of the molecular aspects of interindividual differences in the metabolism and activation of xenobiotics and other genetic markers [DNA-restriction fragment length polymorphisms (RFLPs), mutations, and functional loss of specific genes in carcinogenesis] is an emerging new field that is discussed in the context of genetic susceptibility to cancer. The cytochrome P450 phenotypes and acetylation phenotype are examples of genetic markers that indicate an individual's potential for metabolism of exogenous substances. Further, inherited genetic polymorphic markers, e.g., DNA-RFLPs at protooncogene loci (HRAS-1 and L-myc) have been examined in a case-control study of lung cancer. Data concerning mutations of protooncogenes (H-, K-, and N-RAS) and tumor suppressor genes (retinoblastoma and p53 genes) in various common cancers are providing evidence of multiple genetic lesions that occur during the multistage process of carcinogenesis. PMID- 1910604 TI - An overview on biological markers in reproductive and developmental toxicology: concepts, definitions and use in risk assessment. AB - Reproduction and development are complex couple-dependent processes. Risk assessment for these health outcomes requires the use of biomarkers to link exposures to disease. Biological markers of susceptibility, external dose, internal dose, biologically effective dose, early or late biological responses, altered reproductive or developmental function, and reproductive or developmental disease are introduced. Using these biomarkers it is possible to define a biologically based risk assessment methodology for reproductive and developmental toxicity. Risk assessment for reproductive toxicity requires definition of male and female fecundity, couple-specific factors, spontaneous abortion rate, and other factors. Using using sperm count as a biomarker for male fecundity, an example of a reproductive risk assessment using biomarkers is performed. PMID- 1910605 TI - Hemoglobin adducts as biomarkers of exposure to and metabolic activation of carcinogenic tobacco-specific nitrosamines. AB - The carcinogenic tobacco-specific nitrosamines N'-nitrosonornicotine (NNN) and 4 (methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) form hemoglobin adducts in laboratory animals and humans. These adducts release 4-hydroxy-1-(3-pyridyl)-1 butanone (HPB) upon mild base hydrolysis. HPB released from human hemoglobin can be quantified by gas chromatography-mass spectrometry. It is the only available biochemical marker for determination of exposure to, and metabolic activation of, carcinogens present only in tobacco. Levels of HPB were highest in snuff-dippers, followed by smokers and nonsmokers. Large interindividual variations in adduct levels were observed. The relationship between HPB levels in globin and DNA of rats treated with NNK has been investigated in order to aid in interpretation of the data from humans. These studies have provided the initial database for understanding the metabolic activation of tobacco-specific nitrosamines in humans. PMID- 1910606 TI - Roles of multiple accessory molecules in T-cell activation. AB - Accessory molecules expressed on T cells can mediate adhesion between T cells and other cells, or the extracellular matrix. The same T-cell accessory molecules participate in a dialogue with their ligands (counter-receptors) on the antigen presenting cells, and elicit signals that determine the specifics of activation and subsequent differentiation of the T cells and antigen-presenting cells. PMID- 1910607 TI - Lymphokines and the immune response: the central role of interleukin-2. AB - A number of recent and past reports on the in vitro and in vivo roles of interleukin-2, interleukin-4, interferon-gamma and tumor necrosis factor-beta suggest that interleukin-2 plays a general role in the immune response. The other three lymphokines often play directive roles that determine the kind of response that occurs. PMID- 1910608 TI - Cytokines: is there biological meaning? AB - In the immune system, amidst the bewildering array of cytokine functions, it is sometimes difficult to discern the relative physiological importance of functions that have been determined in tissue culture. Cytokine functions are indeed complex, but the analysis of relatively simple regulatory networks suggests that activities determined in vitro are highly relevant to genuine physiological functions. PMID- 1910609 TI - Cytokine receptors. AB - The molecular characterization of cytokine receptors has progressed rapidly over the past 5 years as a result of availability of radiolabeled cytokines, as well as the identification or creation of cell lines that express significant numbers of receptors at the cell surface. This explosion in research effort has led to establishment of multiple cytokine-receptor gene families and the realization that inhibition of cytokine function at the level of ligand-receptor interaction may be an important area for therapeutic drug development. PMID- 1910610 TI - T-cell-mediated cytotoxicity. AB - There are two competing theories to explain the mechanism(s) by which cytolytic T lymphocytes kill target cells: granule exocytosis of a pore-forming protein, and contact-induced internal disintegration. Accumulated evidence supports alternative pathways in lymphocytoxicity, possibly reflecting distinct effector functions expressed by different killer cells and cells at different stages of activation. PMID- 1910611 TI - Cell-surface enzymes and lymphocyte functions. AB - Recent studies have provided insights into the enzymatic functions of many surface molecules expressed by monocytes and lymphocytes. These ectoenzymes act as cell-differentiation markers of lymphomonocytic lineages; some of them are also involved in activation, signal-transduction and cell-matrix adhesion processes, as well as in the regulation of biological responses of bioactive peptides. PMID- 1910612 TI - T-cell-mediated activation of macrophages. AB - Functionally diverse subpopulations of macrophages and lymphocytes, a wide array of stimulatory signals, and an enormous effector repertoire of activated macrophages keeps this field dynamically active. We review new advances in the identification of cytokines that interact to activate macrophages, and in the discovery of effector molecules used by activated macrophages to destroy their targets. PMID- 1910613 TI - Antigen presentation to B cells. AB - B lymphocytes encounter antigen within the body, which causes them to undergo clonal expansion, affinity maturation and differentiation to antibody-forming cells. How they come into contact with the immunogen, and the subsequent response induced is the subject of several recent reports. PMID- 1910614 TI - Signal transduction in B cells. PMID- 1910615 TI - Control of isotype switching by T cells and cytokines. AB - Since the discovery that isotype switching is mediated by a somatic rearrangement event, progress in the field of isotype switching has come a long way: switch factor activity for several T-cell-derived cytokines has been discovered. The mechanism of action of these switch factors seems to be related to their ability to increase or decrease the transcriptional activation of particular switch regions. We have, however, yet to fully understand this important step in isotype regulation. PMID- 1910616 TI - Signals arising from antigen-presenting cells. AB - It has been customary to consider that antigen-presenting cells provide, in addition to the presented antigen, a second or co-stimulatory signal that leads to T-cell growth and effector function. The recent literature indicates that this two-signal notion oversimplifies the function of antigen-presenting cells. Instead it is useful to consider four groups of events: the formation of peptide MHC complexes, the role of soluble cytokines, the action of antigen-presenting cell-T cell molecular couples distinct from the receptor for peptide MHC, and the function of antigen-presenting cells in situ. PMID- 1910618 TI - Lymphocyte activation and effector functions. PMID- 1910617 TI - Homing receptors and addressins. AB - Molecular cloning of several homing receptors and their placement within unique families of adhesion receptors over the past 2 years will now permit detailed analyses of structure, function and regulation. Novel tools have significantly contributed to the characterization of carbohydrates as essential parts of the recognition site in addressins whose molecular structures remain to be elucidated. PMID- 1910620 TI - Whose rights come first? PMID- 1910619 TI - Garlic compounds modulate macrophage and T-lymphocyte functions. AB - Organosulfur compounds of garlic have been shown to inhibit growth of animal tumors and to modulate the activity of diverse chemical carcinogens. There is also evidence that garlic may modulate antitumor immunity. In this study, we determined the effects of an aqueous garlic extract and a protein fraction isolated from the extract on the chemiluminescent oxidative burst of the murine J774 macrophage cell line and thioglycollate-elicited peritoneal macrophages obtained from BALB/c mice. T-lymphocyte activity was determined using mouse splenocytes incubated with phytohemagglutinin, labeled with [3H]-thymidine and assayed for lymphoproliferation. Significant dose-related augmentation of oxidative burst was observed with garlic extract and the protein fraction. The protein fraction also enhanced the T-lymphocyte blastogenesis. The data suggest that garlic compounds may serve as biological response modifiers by augmenting macrophage and T-lymphocyte functions. PMID- 1910621 TI - Diminished expression of interleukin-2 receptors in vivo after prior chemotherapy in advanced cancer patients receiving recombinant interleukin-2. AB - In a phase I/II dose escalation study performed at our institution, a total of 14 advanced metastatic cancer patients received between 4 and 16 weeks of subcutaneous recombinant interleukin-2. Doses were escalated at weekly intervals, starting at 1.8 million IU/m2/day up to a maximum dose of 14.4 million U/m2 daily. When comparing patients with (n = 4) and without (n = 7) prior chemotherapy on day 0 (i.e., before rIL-2), both patient groups exhibited Tac IL 2 receptor (CD25) positive peripheral blood lymphocytes at equal levels of positivity (8%). In contrast, 4-week systemic treatment with subcutaneous rIL-2 at escalating dose levels revealed a significant difference in the up-regulation by interleukin-2 of CD25 cell surface receptor. Thus, after 4 consecutive weeks of treatment, patients without previous chemotherapy showed a mean CD25 positivity of peripheral blood lymphocytes at 38%, as compared with 22% in patients who did receive prior chemotherapy (p less than 0.05). These data suggest that chemotherapy pretreatment may have a significant effect on biological response to rIL-2 in vivo. PMID- 1910622 TI - Continuous infusion interleukin-2 and tumor-derived activated cells as treatment of advanced solid tumors: a National Biotherapy Study Group Trial. AB - Metastases from patients with solid tumors were harvested from 196 patients for the purpose of growing tumor-derived activated cells (TDAC). Cells were prepared from autologous tumor cultures by incubation with Interleukin-2 (IL-2) followed by repeated exposure to tumor antigen and/or anti-CD3 monoclonal antibody. Initial growth success was achieved in 66%; 45/56 (80%) of these early cultures were subsequently expanded for in vivo therapy. It took a mean of 69.4 +/- 24.0 days to grow TDAC for treatment. Thirty-eight patients were treated with cyclophosphamide (1 g/m2) on day one followed by a 96-hour continuous infusion of IL-2 (18 x 10(6) IU/m2/day) on days 2-5 and approximately 10(11) TDAC on day 2. Patients subsequently received monthly IL-2 as a 96-hour constant infusion if their cancers were stable or regressing. Median age was 51 yrs; 58% were male. Performance status was 0-1 in 64%, 29% had lung metastases; 34% had liver metastases. The usual IL-2 toxicities were seen. Responses were seen only in 1/38 patients (3%); a partial response in a patient with lymphoma. Forty-two percent were stable 90 days post-treatment, the rest were progressive or inevaluable. We conclude that a treatment plan for IL-2/TDAC is technically difficult, costly, and not practical under these conditions. Clinical results to date are not clearly different than those obtained with other IL-2 regimens. PMID- 1910623 TI - Continuous infusion of interleukin-2 and cyclophosphamide as treatment of advanced cancers: a National Biotherapy Study Group Trial. AB - We have evaluated the effect of Interleukin-2 [IL-2] after Cyclophosphamide (C) chemotherapy in 41 patients with metastatic cancer. IL-2 was given as a continuous infusion priming cycle 36 hours after C at 1 gm/m2 intravenously. In 39 evaluable patients, there were no complete remissions [CR], 2 partial remissions [PR], and 1 had a minor response [MR]. Stable disease for 30 days was seen in 16 patients whereas 20 progressed. The durations of partial and minor responses were brief, ranging from 1-6 months. Grade 3-4 neutropenia was seen in 41%. This was more severe than seen with IL-2 alone or IL-2 combined with lower doses of C. The marrow suppression was due to the chemotherapy. This combination of IL-2 and C appears to be reasonably well tolerated by patients, but toxicity is greater and the response rate is no better than results achieved by IL-2 alone. Responses of 26 patients with renal cancer appear to be inferior to our historical data using IL-2/LAK cells without C. Immune monitoring demonstrated changes expected with C chemotherapy (i.e., a non-selective decline in immune function). C induced no further differences in IL-2 induced changes in immune function. PMID- 1910624 TI - Decreased mortality of Norman murine sarcoma in mice treated with the immunomodulator, Acemannan. AB - An extract from the parenchyma of Aloe barbadensis Miller shown to contain long chain polydispersed beta (1,4)-linked mannan polymers with random O-acetyl groups (acemannan, Carrisyn) was found to initiate the phagocyte production of monokines that supported antibody dependent cellular cytotoxicity and stimulated blastogenesis in thymocytes. Acemannan, in both enriched and highly purified forms, was administered intraperitoneally to female CFW mice into which murine sarcoma cells had been subcutaneously implanted. The rapidly growing, highly malignant and invasive sarcoma grew in 100% of implanted control animals, resulting in mortality in 20 to 46 days, dependent on the number of cells implanted. Approximately 40% of animals treated with acemannan at the time of tumor cell implantation (1.5 x 10(6) cells) survived. Tumors in acemannan-treated animals exhibited vascular congestion, edema, polymorphonuclear leukocyte infiltration, and central necrosing foci with hemorrhage and peripheral fibrosis. The data indicate that in vivo treatment of peritoneal macrophages stimulates the macrophage production of monokines, including interleukin-1 and tumor necrosis factor. The data further indicate that sarcomas in animals treated i.p. with acemannan at the time of tumor cell implantation were infiltrated by immune system cells, became necrotic, and regressed. The combined data suggest that acemannan-stimulated synthesis of monokines resulted in the initiation of immune attack, necrosis, and regression of implanted sarcomas in mice. PMID- 1910625 TI - Generation of human autologous melanoma-specific cytotoxic T cells from tumor involved lymph nodes. AB - Cytotoxic T lymphocytes (CTL) specific for autologous human melanoma have been successfully generated in vitro from tumor bearing lymph nodes without any stimulation by the autologous tumor. Tumor-involved lymph node cells (LNC) were cultured in serum free medium (AIM-V) containing 1,000 U/ml of recombinant interleukin-2. The best expansion and specific cytotoxicity of CTL were achieved in 4 to 6 weeks of culture. The predominant populations in cultured LNC-derived CTL were CD2+, CD3+, CD4-, CD8+, CD56-, and HLA-DR+ T cells. These data suggested that tumor-involved LNC may provide an alternative source for the generation of tumor-specific CTL in adoptive immunotherapy. PMID- 1910626 TI - Professor J.Th.G. Overbeek on his eightieth birthday. PMID- 1910627 TI - Aggregation properties of biological amphiphiles. PMID- 1910628 TI - Electron distributions in peptides and related molecules. 1. An experimental and theoretical study of N-acetyl-L-tryptophan methylamide. AB - The thermal vibrations and electron density of N-Ac-L-Trp-NHMe have been analyzed using single-crystal X-ray diffraction data measured at 103 K with Mo K alpha radiation to a resolution corresponding to (sin theta max)/ lambda = 1.17 A-1. Measurements of 10,527 reflections gave 4913 unique data [R(int)(magnitude of F2) = 0.019] of which 2641 had I greater than 3 sigma (I). A multipolar atomic density model was fitted [R(magnitude of F) = 0.028] in order to calculate phases for the crystal structure factors and map the valence-electron distribution. The phase problem for determining deformation densities by Fourier synthesis for noncentrosymmetric crystals is discussed. The experimental density agrees well with the theoretical density from an ab initio SCF molecular wave function calculated at the crystallographic molecular geometry with a split-valence basis set. Both the experimental and theoretical analyses confirm that the electron distribution is the same in the two different peptide groups in the molecule. Crystal data: C14H17N3O2, Mr = 259.31, orthorhombic, P2(1)2(1)2(1), Z = 4, F(000) = 522 e from 295 to 103 K; at 295 K, a = 8.152(2), b = 11.170 (2), c = 15.068 (3) A, V = 1372 A3, Dx = 1.26 mg mm-3; at 103 K, a = 8.209 (3), b = 11.016 (2), c = 14.760 (4) A, V = 1135 A3, Dx = 1.29 mg mm-3, mu = 0.083 mm-1 for lambda = 0.7107 A. PMID- 1910629 TI - Structure of the adipate complex [Na2(C6H9O4)2(C6H10O4)].2H2O from neutron diffraction at 220 and 295 K. AB - The crystal structure of sodium hydrogen adipate-adipic acid (2/1) dihydrate, [Na2(C6H9O4)2(C6H10O4)].2H2O, Mr = 518.4, has been determined from neutron diffraction data collected at 220 and 295 K. Crystals are monoclinic, space group C2/m, with Z = 2. At 295 K, a = 9.378 (2), b = 13.379 (5), c = 10.247 (3) A, beta = 95.93 (3) degrees, V = 1278.8 (7) A3, Dn = 1.346, Dm = 1.348 (1) g cm-3 (in dibromomethane/bromobutane), lambda = 1.1588 (2) A, mu = 2.186 cm-1, F(000) = 176.4 fm, R(F2) = 0.108 for all 1995 nonequivalent reflections with sin theta/lambda less than 0.71 A-1. The crystal structure is similar at 220 K except for reduced nuclear mean-square displacements. Hydrogen adipate subunits (called A) are linked end-to-end in infinite chains by very short O...O (2.44 A) hydrogen bonds where the H nuclei are on centers of symmetry within the experimental error. The Na cation is octahedrally coordinated by O atoms from molecules A and also by non-ionized adipic acid molecules (called B). The B molecules have large mean-square nuclear displacements which are described in terms of anharmonicity and disorder. PMID- 1910631 TI - Structural studies of thiophilic N-chloroazasteroids. AB - N-Chloroazasteroids form covalent S-N bonds with thiol groups and so are of interest as chemoselective irreversible binding agents for the active sites of steroid receptors and enzymes. The solid-state structures of N-chloro-3-methoxy 17-aza-D-homo-1,3,5(10)-estratrien-16-one (1), N-chloro-3-methoxy-17-aza-D-homo 1,3,5(10)-estratrien-17a-on e (2) and N-chloro-3-methoxy-16-aza-1,3,5(10) estratrien-17-one (3) were determined to obtain information about the spatial arrangement of the N-Cl groups. Crystal data: (1) C19H24ClNO2, Mr = 333.84, orthorhombic, P2l2l2l, a = 8.0190 (3), b = 12.7175 (5), c = 16.5047 (9) A, V = 1683.2 (1) A3, Z = 4, Dx = 1.317 g cm-3, lambda(Cu K alpha) = 1.54178 A, mu = 20.9 cm-1, F(000) = 712, T = 295 K, R = 0.045 for 1786 observed reflections; (2) C19H24ClNO2, Mr = 333.84, orthorhombic, P2l2l2l, a = 10.9853 (7), b = 11.8216 (5), c = 12.9851 (9) A, V = 1686.3 (2) A3, Z = 4, Dx = 1.315 g cm-3, lambda(Cu K alpha) = 1.54178 A, mu = 20.9 cm-1, F(000) = 712, T = 295 K, R = 0.035 for 1891 observed reflections; (3) C18H22ClNO2, Mr = 319.81, monoclinic, P2l, a = 13.246 (2), b = 7.972 (2), c = 7.696 (3) A, beta = 90.24 (2) degrees, V = 812.7 (4) A3, Z = 2, Dx = 1.307 g cm-3, lambda(Cu K alpha) = 1.54178 A, mu = 21.4 cm-1, F(000) = 340, T = 295 K, R = 0.045 for 1636 observed reflections.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1910630 TI - Structure and thermal vibrations of adenosine from neutron diffraction data at 123 K. AB - The crystal structure of adenosine, C10H13N5O4, Mr = 267.24, has been refined by full-matrix least-squares methods using single-crystal neutron diffraction data (sin theta/lambda less than 0.79 A-1) measured at 123 K. Crystal data at 123 K: monoclinic, P2l, Z = 2, a = 4.7885 (8), b = 10.240 (2), c = 11.772 (2) A, beta = 99.59 (2) degrees, V = 569.2 A3, lambda = 1.0402 (1) A, Dn = 1.559 Mg m-3, mu = 191.1 m-1, F(000) = 175.72 fm, R(F2) = 0.044, wR(F2) = 0.055, S = 1.13 for 2450 reflections with F2 greater than 0.0. Bond lengths and angles have e.s.d.'s less than 0.002 A and 0.1 degrees for non-H atoms and less than 0.004 A and 0.3 degrees for H atoms. Values are in general agreement with those previously obtained from room-temperature X-ray data and with those obtained for 9 methyladenine by neutron diffraction at 126 K. Small displacements of amino H atoms from the least-squares plane through the non-H atoms of the adenine part appear to be the result of hydrogen bonding. There is an intermolecular interaction C2--H2...O2' with an H...O distance of 2.20 A. In its thermal vibrations, the adenosine molecule behaves as two rigid segments with a torsional libration about the glycosidic bond of 14.4 deg2 at 123 K. The force constant for this libration, as determined from the diffraction data, is 73 (10) J mol-1 deg 2. PMID- 1910632 TI - Exact random-walk models in crystallographic statistics. VI. P.D.F.'s of magnitude of [E] for all plane groups and most space groups. AB - An exact calculation of the probability density function (p.d.f.) of magnitude of [E], the magnitude of the normalized structure factor, can be developed in terms of Fourier and Fourier-Bessel series whose coefficients can be expressed in terms of the characteristic function. This article provides the formulae for atomic contributions to such characteristic functions. The results presented in this study are applicable to all the plane groups and to 206 three dimensional space groups. Only the space groups isomorphous to the cubic point groups 432, 43m and m3m were omitted due to the complexity of the resulting expressions and the small deviations of the corresponding densities from the central-limit-theorem approximation, which have been observed in simulations for extreme atomic heterogeneities. Representative derivations illustrating the problems and techniques of their solution are provided. All the theoretical results have been computed numerically and compared with simulated distributions. Some results of these computations are illustrated in the accompanying paper, Part VII of this series [Rabinovich, Shmueli, Stein, Shashua & Weiss (1991). Acta Cryst. A47, 336 340]. PMID- 1910633 TI - Exact random-walk models in crystallographic statistics. VII. An all-space-group study of the effects of atomic heterogeneity on the P.D.F.'s of magnitude of [E]. AB - Exact expressions have been found for the probability density functions (p.d.f.'s) of the magnitude of the normalized structure factor for all the two dimensional and most three-dimensional space groups [Part VI: Rabinovich, Shmueli, Stein, Shashua & Weiss (1991). Acta Cryst. A47, 328-335]. The results of that investigation are used in the present article to examine some effects of atomic heterogeneity, in the various space-group symmetries, on the p.d.f.'s. Some typical comparisons are made between p.d.f.'s based on the central limit theorem and p.d.f.'s computed from exact formulae. In addition, the exact results are compared to histograms of simulated values of magnitude of [E]. It is found that the p.d.f.'s for some space groups are influenced rather strongly by the presence of outstandingly heavy scatters, but they are quite insensitive to the presence of such scatterers in other space groups. The often made general statement 'The presence of outstandingly heavy scatterers may invalidate the indications of Wilson's statistics' is made more precise here, insofar as it depends on the particular space group. PMID- 1910634 TI - On integrating the techniques of direct methods with anomalous dispersion. II. Statistical properties of the two-phase structure invariants. AB - Results of a statistical study of probabilistic estimates of two-phase structure invariants (TPSI) for Friedel pairs in the case of single-wavelength anomalous scattering are reported. Numerical analysis of the TPSI sign, magnitude and error distributions shows that the concise formula for TPSI by probability theory [Hauptman (1982). Acta Cryst. A38, 632-641; Giacovazzo (1983). Acta Cryst. A39, 585-592] has desirable statistical properties. Computational results for the known structures of cocaine methiodide (N-methylcocaine iodide) and of cytochrome c550 and its PtCl2-4 derivative show that when [E[ values are large most of the signs of the TPSI are correctly determined - for [E[ greater than 1.0, 90% or more of the TPSI signs are positive as predicted - and the errors in the estimated TPSI magnitudes do not exceed approximately 10% for [E[ greater than 1.0 in the small-molecule case or approximately 50% for [E[ greater than 1.5 in the macromolecular case. These results suggest that the theory will be useful for estimating the TPSI for unknown structures. PMID- 1910635 TI - Phase determination by polarized dispersion in vanadyl sulfate pentahydrate. AB - Anomalous-scattering tensors for V measured with linearly polarized synchrotron radiation in VOSO4. 5H2O near the K-absorption edge exhibit anisotropy as much as 4 units in f" and +/- 2 units in f'. This polarized dispersion causes the diffraction intensity to change when a crystal is turned around a diffraction vector and is the basis of a new way to obtain phases of structure factors. PMID- 1910636 TI - The calcium antagonists in the 1990s. An overview. AB - The calcium antagonists are effective in the treatment of essential hypertension. This quality, in addition to their ability to inhibit atherosclerotic lesion formation, may make them superior to other classes of antihypertensive agents in preventing vascular complications of mild to moderate hypertension. Preliminary results of clinical trials suggest that the calcium antagonists retard the progression of early atherosclerotic lesions in native coronary arteries and saphenous vein grafts, but have less effect on established lesions. Further study is needed to determine whether these agents have a favorable effect on the overall clinical outcome of patients with coronary artery disease. Clinical trials also suggest that the calcium antagonists retard the progression of renal insufficiency in hypertensive patients by mechanism(s) that do not depend on blood pressure lowering per se. Prospective studies with larger numbers of patients are needed to determine whether these apparent renoprotective effects are sustained for the long term in both diabetic and nondiabetic hypertensive populations. The dihydropyridine calcium antagonists are effective in reducing brain damage and mortality secondary to acute ischemic stroke. It is still unknown whether they are also effective in the primary and secondary prevention of ischemic stroke, and whether other classes of calcium antagonists are useful in the prevention and/or treatment of ischemic stroke. The potential antiatherosclerotic and cardio-, neuro-, and renoprotective effects of the calcium antagonists, coupled with their lack of adverse metabolic effects, have defined an expanding therapeutic role for these agents in the 1990s. PMID- 1910637 TI - Diltiazem inhibition of sodium-induced calcium release. Effects on energy metabolism of heart mitochondria. AB - The effect of d-cis-diltiazem, a calcium antagonist, on calcium transport processes of rabbit heart mitochondria was studied in vitro. Up to a concentration of 350 mumol/L, the drug produced very little effect on calcium uptake; however, the rate of sodium-induced calcium release progressively decreased as diltiazem concentrations increased. The diltiazem concentration required to inhibit half the rate (IC50) of calcium release induced by 10 mmol/L of sodium chloride was 4.5 mumol/L. The IC50 of the 1-cis isomer of diltiazem was 350 mumol/L, indicating that the inhibitory effect is stereospecific. Of the calcium antagonists, d-cis-diltiazem most effectively inhibited sodium-induced calcium release from heart mitochondria. The consequences of that inhibitory effect were then investigated. When the calcium uptake process was not blocked, the progressive inhibition of sodium-induced calcium release by diltiazem resulted in a net gain of calcium by mitochondria in vitro, suggesting that a similar effect in vivo may increase intramitochondrial calcium. To determine whether sodium-induced calcium release affects respiration and whether diltiazem prevents this effect, we studied the effects of sodium ion and diltiazem on respiration and oxidative phosphorylation of isolated mitochondria. Sodium was found to decrease the rate of state 3 respiration, respiratory control index, and rate of oxidative phosphorylation; diltiazem prevented these effects on mitochondria. Diltiazem's effect was attributed to increased intramitochondrial calcium because of inhibited sodium-induced calcium release and activation of calcium-sensitive dehydrogenases in the matrix. The data indicate that diltiazem may increase the rate of ATP synthesis by mitochondria due to increased intramitochondrial calcium resulting from inhibition of sodium induced Ca2+ release. PMID- 1910638 TI - Hypertension and the coronary circulation. With special attention to endothelial regulation. AB - Calcium channel antagonists are commonly used to treat chronic hypertension. Several studies of intact vascular tissues suggest that these agents may impair the production of the endothelium-derived relaxing factor and alter endothelium dependent vascular relaxation. These studies are difficult to interpret because the calcium channel antagonist may have direct effects on vascular smooth muscle. In our study, a chemiluminescence assay was used to measure the release of nitrogen oxides from bovine aortic endothelial cells (BAEC) grown in monolayer. Under basal conditions, the release of nitrogen oxides was 0.2 nmol/100 mg protein and was increased approximately two-fold by 0.1 micrograms, bradykinin. Incubations with diltiazem, verapamil, and nifedipine for 60 min did not influence the basal and bradykinin-stimulated release of nitrogen oxides by BAEC. These data illustrate that the production of the endothelium-derived relaxing factor is not altered by the calcium channel antagonist, and are compatible with an absence of L-type calcium channels in vascular endothelial cells. Chronic hypertension produces myriad adverse effects in the coronary circulation. After coronary occlusion, infarct size, expressed as a function of myocardial mass perfused, is increased by 33%, and the wavefront of infarction from subendocardium to subepicardium is hastened. Both chronic and acute hypertension produce numerous abnormalities of coronary flow regulation. These include impairments of autoregulation, changes in vascular responsiveness, and alterations of endothelial cell function. Many of these may worsen the clinical consequences of ischemic heart disease, either by producing structural alterations of the coronary vasculature, or equally importantly, by altering coronary vascular responsiveness to either mechanical or neurohumoral stimuli.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1910639 TI - Growth factors and cardiovascular structure. Implications for calcium antagonist therapy. AB - Abnormalities of cellular growth regulation are integral to the development of cardiovascular disorders such as atherogenesis, ventricular hypertrophy, and diabetic glomerulopathy. Moreover, cellular growth is in large measure controlled by peptide and nonpeptide growth factors that mediate their actions, in part, through the transcriptional regulation of normal cellular genes called protooncogenes. Because angiotensin II is one such growth regulatory factor and because changes in intracellular calcium are intimately involved in the action of angiotensin and other growth factors, it is likely that inhibitors of angiotensin action and calcium-channel-blocking agents will be found to have useful growth regulatory properties. PMID- 1910641 TI - Calcium antagonists and the kidney. Implications for renal protection. AB - During the past decade, attention has been focused on the effects of calcium antagonists on renal function. When administered in vitro to the isolated perfused kidney (IPK), calcium antagonists exhibit consistent actions, permitting characterization of their renal effects. Calcium antagonists do not affect the vasodilated IPK, but do dramatically alter the hemodynamic response of the kidney to vasoconstrictor agents. Our recent studies using the isolated perfused hydronephrotic rat kidney model, which permits direct visualization of afferent and efferent arterioles, demonstrate that the preferential augmentation of glomerular filtration rate (GFR) observed in the IPK is attributable to preferential vasodilation of preglomerular vessels. Although the clinical implications of such observations have not been fully delineated, recent studies indicate that calcium antagonists exert salutary effects on renal function in clinical settings, characterized by impaired renal hemodynamics such as radiocontrast-induced nephrotoxicity and transplant-associated acute renal insufficiency. It is apparent, however, that the salutary effects of calcium antagonists on renal hemodynamics recommend their use in the management of essential hypertension. PMID- 1910642 TI - Renal effects of calcium antagonists in diabetes mellitus. An overview of studies in animal models and in humans. AB - A number of studies based on animal models of both diabetes and renal insufficiency have shown that adequately reducing blood pressure attenuates the progression of glomerulosclerosis and decreases urinary protein excretion. Furthermore, compared with conventional antihypertensive therapy, angiotensin converting enzyme (ACE) inhibitors show a greater benefit in reducing these parameters. Nineteen published animal studies have investigated the effects of calcium antagonists on renal hemodynamics and glomerulosclerosis, but only three of them have evaluated the use of calcium antagonists with models of diabetes. Of six micropuncture studies based on a 1 5/6 nephrectomy model of renal insufficiency, five demonstrated reduced efferent arteriolar resistance, two showed reduced glomerular capillary pressure (PGC), and two showed significantly reduced proteinuria and glomerulosclerosis. Studies using nifedipine with both the unilaterally nephrectomized DOCA salt rat model and the 1 5/6 nephrectomy model demonstrated reduced proteinuria and glomerulosclerosis that was independent of reduced PGC. Two separate micropuncture studies of the spontaneously hypertensive rat model also found reduced efferent arteriolar resistance and PGC as well as proteinuria. Finally, studies of Dahl "salt sensitive" rats showed an early decrease in glomerulosclerosis without a significant change in either proteinuria or glomerulosclerosis after five weeks. The results of eleven clinical studies of diabetic patients have been published; they showed divergent effects of calcium antagonists on renal function and urinary protein excretion. In the various animal models, the divergent renal hemodynamic and histologic effects reported for calcium antagonists may be largely due to the equality of blood pressure reduction, the varied baseline hemodynamic profiles, and the divergent status of the renin-angiotensin system.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1910640 TI - A single mechanism to explain the effect of calcium on renal function. AB - It is known that calcium induces the formation of potent vasodilators in endothelial cells and vasoconstriction in smooth muscle cells, whereas in the renal parenchyma, it modulates sodium excretion through vascular and tubular mechanisms. Consequently, an increased concentration of calcium in renal circulation may induce a sequence of contrasting hemodynamics and excretory effects depending on the threshold of a particular mechanism that is first being stimulated. In order to identify this sequence of responses and their respective thresholds, we infused into the renal artery of anesthetized dogs progressively increasing doses of calcium gluconate that ranged from 1 to 400 micrograms/kg/min. The administration of 1, 10, and 100 micrograms/kg/min of calcium gluconate was followed by a significant increase in urinary excretion of PGE2 and 6-keto-PGF1 alpha and by a marked diuresis and natriuresis without altering renal blood flow (RBF) or glomerular filtration rate (GFR). Renin release was increased by 80% only during the infusion of the 10 micrograms/kg/min dose. The intrarenal infusion of a 400 micrograms/kg/min dose of calcium produced marked decreases in RBF and GFR, while urine sodium excretion (UNaV), UPGE2V, and U6-keto-PGF1 alpha V continued and were markedly elevated. During all these maneuvers, mean arterial pressure remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1910643 TI - 7 ways to motivate your employees. PMID- 1910644 TI - A little office etiquette can go a long way to improve professionalism. PMID- 1910646 TI - These 10 secrets can promote the successful sale of your practice. PMID- 1910645 TI - Survey shows most Americans don't practice what they know about care. PMID- 1910647 TI - Autonomic dysreflexia. A survey of current treatment. AB - Autonomic dysreflexia (AD) is a syndrome that often occurs in patients with spinal cord injuries above T-6 and can have life-threatening results if not properly managed. The hypertension associated with AD can cause a great deal of morbidity and mortality, requiring quick and effective blood pressure reduction. Both pharmacologic and nonpharmacologic methods are used to prevent or alleviate the symptoms associated with an acute episode of AD. We found that current literature is lacking in controlled, prospective, randomized studies comparing the efficacy of various medications used in the treatment of AD. We conducted a nationwide survey to determine the consensus among clinicians concerning the management of AD. The survey was designed to determine the current clinical status of AD, to assess methods of treatment being used and to summarize and give a rationale for the drugs most commonly prescribed. Finally, a suggestion for a wallet-sized card briefly outlining effective treatments of AD in an emergency situation is included. Results indicate that most clinicians feel that after nonpharmacologic measures have failed, antihypertensive medication is useful in controlling the symptoms of AD while the inciting cause is being found and treated. Agents used most frequently include, but are not limited to, nifedipine, phenoxybenzamine, prazosin, mecamylamine and nitrates. PMID- 1910648 TI - Inpatient comprehensive rehabilitation after liver transplantation. AB - Liver transplantation has become a standard treatment for liver failure and is covered by Medicare. Transplantation has up to an 80% survival rate; however, the postoperative course can include many complications, a long hospital admission and the need for the involvement of many medical and therapeutic disciplines. Ideally, this is provided by a coordinated comprehensive rehabilitation program, but descriptions of this type of management are absent from the literature. This report describes the case of a 54-yr-old male with alcoholic cirrhosis who underwent orthotopic liver transplantation. His postoperative course was complicated, and he developed global weakness secondary to hepatic neuropathy with superimposed type II steroid-induced myopathy. Four months after the transplant he was unable to sit up in bed and was admitted to the rehabilitation unit. The patient required two subsequent admissions to the acute hospital for complications; however, close cooperation between the surgical transplant team and the rehabilitation team facilitated functional improvement and enabled discharge to home in less than 8 wk. At discharge, the patient was independent in bed mobility, transfers and self-care, and he was ambulating with contact guard. Medical issues, including evaluation, medications and possible complications in the rehabilitative phase are discussed. PMID- 1910649 TI - Footwear and posture. Compensatory strategies for heel height. AB - The belief that wearing high-heeled shoes increases lumbar lordosis is firmly ingrained in clinical folklore. Proponents of negative heel footwear argue that because high positive heels increase the lumbar lordosis, negative heels will decrease the lumbar lordosis. Quantitative documentation of the assumption regarding high heels is not to be found in the literature, although sporadic attempts to prove this assumption have been made throughout the 20th Century. Although other effects, such as decreased gait speed and step length, and increased knee flexion at heel strike have been found in more than one study, no increase in lumbar lordosis has been found. Where an actual decrease in lordosis has been found, authors tend to explain it away as inconsistent with what every clinician feels that he or she has observed. We felt it appropriate, then, to conduct both a static and a dynamic study to assess the effects of heel height on lumbar spine and lower limb joint kinematics in the sagittal plane, as well as other strategies to compensate for heel height. The results indicate that the greatest compensation is at the ankle and knee. Where a significant effect occurred in the lumbar spine (males, dynamic study), high heels decreased the lumbar lordosis, i.e., resulted in less swayback rather than more. PMID- 1910650 TI - Exercise-induced myokymia with congenital spinal stenosis. AB - Myokymia and myokymic discharges are observed in a variety of neurologic conditions. An unusual case of myokymia induced by exercise and febrile illness presented in an 11-yr-old male with congenital spinal stenosis. Myokymia was not generalized, but occurred below the level of his umbilicus. We hypothesize that local spinal cord ischemia was the underlying mechanism for this rare phenomenon. The pathophysiology, clinical features and electrodiagnostic findings of myokymia are reviewed. PMID- 1910651 TI - The effect of physical therapy for children with motor delay and cerebral palsy. A randomized clinical trial. AB - Physical therapists recommend neurodevelopmental therapy for cerebral palsy, but its effectiveness has not been fully established. A randomized controlled trial was undertaken to compare the effects over 6 months, of weekly (intensive) and monthly (basic) neurodevelopmental therapy on the motor development of young children with suspected cerebral palsy. Subjects were no older than 18 months when referred for physical therapy because of a motor delay. All those meeting specified criteria were assessed on seven motor development tests: reflex activity, postural reactions, gross motor ability, fine motor skills, mental functioning, dominance of abnormal movement patterns and ability to participate in activities of daily living. The average proportional change in aggregate motor development for the 17 infants on the weekly (intensive) regimen was substantially better than that for the 12 on the monthly (basic) regimen, after adjusting for the child's age, whether the child was born at term or not, and mother's education. A statistical test led to an equivalent of a Student's t = 3.49, which with 24 df was associated with P = 0.0019 (two-sided). PMID- 1910652 TI - The interobserver reliability of the revised American Spinal Injury Association standards for neurological classification of spinal injury patients. AB - To test the interobserver reliability of clinicians using the American Spinal Injury Association's 1989 revised "Standards for Neurological Classification of Spinal Injury Patients," two quizzes were given to 15 house officers and physician faculty members of a department of Physical Medicine and Rehabilitation. The first quiz consisted of five spinal cord injury cases of varying degrees of complexity. The participants were asked to classify each case with respect to sensory level, motor level, zone of injury and Frankel classification by using the original standards. Two months later, after a brief explanation of the significant changes in the revised standards, the same group was given five slightly different cases to classify. With the use of the 1989 revision of the standards, the percent correct improved for Frankel grade (65 81%), motor level (59-85%), sensory level (71-93%) and zone of injury (31-89%). Many of the same type of errors were repeated in both quizzes, i.e., T-12 and L-1 sensory level distinction and the classification of thoracic motor levels. We conclude that the interobserver reliability for the revised ASIA standards, although improved, continues to be less than optimal. We recommend that changes clarifying sensory levels near the inguinal ligament and motor level classification with very incomplete injuries be made in the standards. In addition, training methods should be developed to improve the interobserver reliability of the standards when they are used by clinicians and researchers. PMID- 1910655 TI - Electrodiagnostic medicine in PM&R. Lead now or follow later: a commentary. PMID- 1910653 TI - Atrial fibrillation associated with autonomic dysreflexia. AB - Autonomic dysreflexia is an acute disorder of autonomic homeostasis occurring in persons with spinal cord lesions above the major splanchnic sympathetic outflow. Atrial fibrillation is a serious cardiac arrhythmia characterized by disorganized atrial depolarization and an irregular ventricular response. Previously reported complications of autonomic dysreflexia have included seizures, strokes and cardiac arrhythmias other than atrial fibrillation. We present a 60-yr-old man with C-5 incomplete quadriplegia in whom atrial fibrillation was apparently induced by an episode of autonomic dysreflexia. Mechanisms by which autonomic dysreflexia may cause this arrhythmia include altered cardiac autonomic tone as well as atrial distention. The simultaneous occurrence of autonomic dysreflexia and atrial fibrillation poses special diagnostic problems and treatment risks. Atrial fibrillation incidence increases with age in the general population. With the aging of the spinal cord-injured population, we expect to see more episodes of atrial fibrillation associated with autonomic dysreflexia. PMID- 1910654 TI - The pronator syndrome. An evaluation of dynamic maneuvers for improving electrodiagnostic sensitivity. AB - The role of three test maneuvers (elbow flexion, forearm pronation and finger flexion against resistance) in improving sensitivity of conventional nerve conduction studies used in cases of suspected pronator teres syndrome were evaluated in 11 healthy control subjects and 10 patients with the clinical diagnosis of pronator teres syndrome. Stimulation of the median nerve was performed above and below the elbow before exercise and immediately after the test maneuvers; the resultant median motor and sensory responses were recorded. Before and after exercise, median motor and sensory responses (e.g., amplitude, latency, velocity) did not differ significantly between the two groups; only one patient with suspected pronator teres syndrome developed sensory amplitude changes after exercise. We concluded that these test maneuvers did not significantly improve the sensitivity of conventional nerve conduction studies in the diagnosis of pronator teres syndrome. PMID- 1910656 TI - Superior mesenteric artery syndrome in a child with brain injury. Case report. AB - Superior mesenteric artery syndrome is a rare cause of upper intestinal obstruction in both adults and children. This report describes an 11-yr-old boy with severe traumatic brain injury who developed superior mesenteric artery syndrome while undergoing rehabilitation. After the onset of postprandial bilious vomiting, an upper gastrointestinal x-ray series revealed abrupt obstruction of flow of barium at the third part of the duodenum with dilation of the first and second portions and antiperistaltic flow of barium. He was treated nonsurgically and feeding was accomplished using a tube passed into the jejunum. No recurrence was reported at follow-up 2 yr later. Prolonged recumbency and recent weight loss were considered as the precipitating factors. PMID- 1910657 TI - Medical economics of PM&R. I. Current financial trends and the future of PM&R. PMID- 1910658 TI - [Epidemiologic studies of the effect of alcohol and drugs on psychophysical performance]. AB - In this new epidemiological investigation, it is first of all observed that the proportion of chemical toxicological investigations instituted by the police in the area served by the Institute of Forensic Medicine, University of Tubingen, has not risen despite increases in the use or abuse of drugs and alcohol consumption although 80 per cent of those concerned are car and motorcycle drivers. On the other hand, is has been noticed in recent years that such investigations are instituted especially when the level of blood alcohol measured does not explain the actual condition of the person concerned. Just under 20 per cent of the affected persons denied consumption of a drug, and more than half admitted the use of a drug. Just under one fifth admitted using two drugs. The remainder used three and four agents. In about half of all cases, the statements were confirmed by the result of the chemical toxicological investigations. In contrast to an investigations of our own, the confirmation of the admissions does not correlate with the rising blood alcohol content. About 63 per cent of the 676 cases investigated had taken analgesics, beta blockers or calcium antagonists, hypnotics or sedatives, gastrointestinal agents and psychoactive agents. The percentage of active agents from the benzodiazepine group, which is subject to the Narcotics Law, is especially great. Finally, the blood and urinary levels of benzodiazepines and individual psychoactive agents measured as well as the pertinent blood and urinary alcohol values were compared with the constellations described in the medical examination and the divergences from the data obtained experimentally are discussed. PMID- 1910659 TI - [Recommendation for a legally valid breath alcohol measurement]. AB - Evidential breath-alcohol analysis requires measuring devices which cannot yet be obtained from industrial manufacturers. In order to avoid the influence of environment and breath techniques and to relate the breath-alcohol concentration to a standard temperature of 34 degrees C it is necessary to measure the breath temperature with a special device. The required reliability of measured results can only be obtained with two measuring systems operating independently from each other. When two measuring systems of different analytical specificity towards interfering substances are used, the infrared method allows a widely selective determination of ethanol. This is a prerequisite for the legal calibration of breath-alcohol analysers. PMID- 1910660 TI - [Breath alcohol in relation to blood alcohol: problem with deviant values]. AB - We report 23 cases of considerable differences of the results of breath alcohol analyses and the corresponding blood alcohol analyses observed by seven Institutes of Forensic Medicine in Germany and Austria. The usefulness of breath alcohol analysis on forensic casework at the courts will have to be evaluated on the bases of the possibility of such grave deviations. PMID- 1910661 TI - [Effect of low blood alcohol concentrations in relation to time of day]. AB - The physical performance of 23 persons was tested at different time of day (morning, noon, evening) under the influence of low doses of alcohol (0.8%). The results obtained indicate, that the capability of performing the tests was remarkable reduced. In the evening the effect of alcohol was significantly higher than at noon and morning; the time of recovery was also prolonged. Under these aspects the limit of 0.8% for car drivers in (West) Germany has to be reconsidered. PMID- 1910662 TI - [Falsification of breath alcohol concentration measurement. An experimental and case report]. AB - As a rule, in our comparison of breath alcohol and blood alcohol concentration levels both readings were in agreement. Nevertheless, we repeatedly observed readings showing significant differences for which there was no apparent explanation. In two cases where discrepancies were extreme (breath alcohol concentration greater than 2.0%; blood alcohol concentration, 0.0%) we discovered that the cause was sniffing. The effects of various pharmaceutical drugs were tested. Experimentally the inhalation of liquid gas resulted in ostensible breath alcohol concentration levels of more than 2%. These experiments were reproducible. Consequences for the exployment of alcohol breath testing devices are discussed. PMID- 1910663 TI - [Does the highest judicial ordinance for a new limit value for absolute driving incapacity (BGH 4 StR 297/90, Beschl. v. 28 June 1990) allow unequal treatment of alcohol intoxicated drivers?]. AB - The jurisdiction in the BRD knows a threshold value of the blood alcohol concentration from which on the actual absolute driving unfitness without any further evidence will be assumed. This threshold value has been lowered by the highest german criminal court (BGH) from so far 1.3% to now 1.1 g%. As the determination of the alcohol content takes place in two different procedures as a mean value out of four or five single values, the highest court orders a dispersion control--the standard deviation from 0.03 g% or 0.04 g%. The authors proof that therefore a dissimilar treatment of motor traffic participants under the influence of alcohol may be possible. The reason is to be traced in the different distributions of a single values around the mean value and in the incorrect application of the standard deviation. PMID- 1910664 TI - A miniature Clark-type oxygen electrode using a polyelectrolyte and its application as a glucose sensor. AB - A miniature Clark-type oxygen electrode was fabricated by anisotropically etching silicon. A two-gold-electrode configuration was used and a double-layered gas permeable membrane was formed directly on the electrolyte, poly(vinyl-4 ethylpyridinium bromide) in the sensitive area. These materials improved the electrode's stability in long-term storage and sterilization tolerance to a practical level. The 90% response time averaged 80 s and residual current 10%, with a good linear calibration curve. The oxygen electrode was also used to make an integrated sensor for the simultaneous determination of glucose and oxygen. The glucose sensor's response time was 50-110 s, with good linearity in glucose concentrations between 56 microM and 1.1 mM at 37 degrees C, pH 7.0. PMID- 1910665 TI - In vitro testing of a simply constructed, highly stable glucose sensor suitable for implantation in diabetic patients. AB - We have constructed and tested in vitro a potentially implantable, needle-type amperometric enzyme electrode which is suitable for continuous monitoring of glucose concentrations in diabetic patients. The major requirements of stability during operation and ease of manufacture have been met with a sensor design which involves a simple dip-coating procedure for applying to a platinum base electrode an inner membrane of glucose oxidase immobilised in polyhydroxyethyl methacrylate (pHEMA), and an outer membrane composed of a pHEMA/polyurethane mixture. Sensors were operated at 700 mV for detection of hydrogen peroxide. Calibration curves for the sensor were linear to at least 20 mM glucose and were unaffected by a reduction in PO2 from 20 to 5 kPa. During continuous operation in 5 mM buffered glucose solutions in vitro, sensors suffered no significant loss of response over periods of up to 60 h. Such electrodes are, therefore, useful for development as in vivo glucose sensors. PMID- 1910666 TI - Internal supply of coenzyme to an amperometric glucose biosensor based on a chemically modified electrode. AB - A biosensor for glucose using glucose dehydrogenase immobilized on a chemically modified graphite electrode was supplied with coenzyme, nicotinamide adenine dinucleotide (NAD+), through pores in the material. A graphite rod was hollowed out, leaving 0.3 mm at the end contacting the solution, filled with 10 mM NAD+ and pressurized. The response factor was 40% of that obtained when 2 mM NAD+ was mixed with the sample solution in a flow system. The coenzyme consumption was 11 microliters h-1 representing a 500-fold saving compared to supply through the bulk solution. The biosensor had a linear calibration curve from the detection limit, 1 microM, to 2 mM glucose and a repeatability of 0.3%. The graphite electrode was modified by adsorption of a bis-(benzophenoxazinyl)-terephthaloyl derivative in order to be able to oxidize NADH at 0 mV versus Ag/AgCl, 0.1 M KCl. PMID- 1910667 TI - Detection of human leucocytes by cyclic voltammetry and its application to monitoring of allergic reaction. AB - Cyclic voltammetry was applied to the detection of human leucocytes and the monitoring of allergic reactions. A basal plane pyrolytic graphite electrode with attached leucocytes on a porous nitrocellulose membrane filter was employed as a working electrode. An anodic peak current appeared at 0.33 V versus the saturated calomel electrode (SCE) when the potential of the working electrode was scanned in the range of 0-1.0 V versus SCE. This peak current was attributed to the electrochemical oxidation of serotonin. When egg white was added to leucocytes obtained from patients who were allergic to egg, the peak current decreased owing to degranulation of leucocytes leading to serotonin release. The peak current decreased with increasing allergen concentration in the range of 5-50 micrograms ml-1. Leucocytes did not respond to other allergens such as soybean, milk and dinitrophenylated bovine serum albumin (DNP-BSA). PMID- 1910668 TI - Current developments in optical biochemical sensors. AB - By combining modern fibre optics and opto-electronic instrumentation with chemical and biochemical reagent systems, it has become possible to fabricate optical biosensors. The current state of the art in this development is reviewed in this paper. Many developments describe selective and sensitive methods for sensing bioanalytes and it is likely that such a development will continue to be a very active area of analytical research. However, these biosensing devices can be regarded as successful only if their practicality and reliability can be demonstrated. PMID- 1910669 TI - Determination of urate in undiluted whole blood by enzyme electrode. AB - An amperometric enzyme electrode is described for the assay of urate in undiluted, unstirred whole blood. The electrode used Aspergillus flavus uricase (EC.1.7.3.3) cross-linked to bovine serum albumin by means of glutaraldehyde, sandwiched between a dimethyldichlorosilane-treated microporous polycarbonate membrane and an inner cellulosic H2O2-selective membrane. The resulting device had a low pH dependence, was capable of repeated use in blood, and gave an acceptable correlation with a standard spectrophotometric method. Electrode steady state and dynamic response were found to be dependent upon the amount of enzyme loading, and could be further optimised by the incorporation of catalase in the enzyme layer. PMID- 1910670 TI - Fluorescence polarization immunoassay employing immobilized antibody. AB - The use of an antibody immobilized on latex or silver colloid in fluorescence polarization immunoassay (FPI) is assessed. In FPI it is possible to detect antigens of high molecular weight because the molecular weight of the antibody is effectively increased. In the assay for rabbit immunoglobulin G a limit of detection lower by two orders of magnitude and an assay range wider by one order of magnitude can be obtained in comparison with conventional FPI. The detection limit is 10(-10) mol l-1 and the total assay time for one sample is 8 min. This assay combines a low detection limit with a short assay time. PMID- 1910671 TI - Pharmacological specificity of a nicotinic acetylcholine receptor optical sensor. AB - The pharmacological specificity of a nicotinic acetylcholine receptor (nAChR) optical biosensor was investigated using three fluorescein isothiocyanate (FITC) tagged neurotoxic peptides that vary in the reversibility of their receptor inhibition: alpha-bungarotoxin (alpha-BGT), alpha-Naja toxin (alpha-NT), and alpha-conotoxin (GI) (alpha-CNTX). Kinetic analysis of the time course of binding of FITC-neurotoxins to the nAChR-coated fiber gave association rate constants (k+1) of 8.4 x 10(6) M-1 min-1 for FITC-alpha-BGT, 6.0 x 10(6) M-1 min-1 for FITC alpha-NT and 1.4 x 10(6) M-1 min-1 for FITC-alpha-CNTX. The dissociation rate constants (k-1) for the three neurotoxins were 7.9 x 10(-3) min-1. 4.8 x 10(-2) min-1 and 8.0 x 10(-1) min-1 for FITC-alpha-BGT. FITC-alpha-NT and FITC-alpha CNTX, respectively. The equilibrium dissociation constant (Kd) values for the three toxins. calculated from these rare constants, were similar to published values obtained from tissue responses or ligand binding assays. The optical signal generated by FITC-alpha-NT binding to the nAChR-coated fiber was effectively quenched by agonists and antagonists of the nAChR but not by most of the tested agonists and antagonists of muscarinic cholinergic, adrenergic, glutamatergic, serotonergic, dopaminergic or GABAergic receptors. Interestingly, 5-hydroxy-tryptamine, haloperidol and (+)cis-methyldioxolane gave significant inhibition of FITC-alpha-NT binding to the immobilized receptor. Equilibrium constants of inhibition (Ki) for d-tubocurarine (d-TC) and carbamylcholine (carb) were determined from competition studies using FITC-alpha-CNTX. FITC-alpha-NT or FITC-alpha-BGT as probes for receptor occupancy. When the more reversible probe FITC-alpha-CNTX was used, the Ki value for d-TC was an order of magnitude lower than those determined using the less reversible probes. Ki values for carb however, were independent of the FITC-toxin probe used. PMID- 1910672 TI - Model experiments with integrated optical input grating couplers as direct immunosensors. AB - Using an input grating coupler instrument and monomode optical waveguides, we studied the adsorption of various proteins (e.g. human immunoglobulins G and A (h IgG and h-IgA), and avidin) on the waveguide surface. In model experiments for immunoassays, we also monitored as a function of time the formation of time formation of the immuno-complex Ag-Ab between antigen (Ag) molecules absorbed on the waveguide surface and antibody (Ab) molecules, for example, of adsorbed h-IgG vs anti-h-IgG, anti-goat-IgG (cross-reaction) and anti-h-IgA (negative test). We also studied the affinity reaction between adsorbed protein A and h-IgG. From the measured changes in the effective refractive indices N(TE0) and N(TM0) of the TE0 and TM0 modes, we determined the thickness dF, the refractive index nF, and the surface coverage gamma of the absorbed protein adlayers and of the immuno complexes. PMID- 1910673 TI - When all is said and done.... AB - Dr. Benacerraf describes his experience in training immunologists for a period of over 30 years. He then analyzes the circumstances in which selected discoveries were made in his laboratory and the events and reasoning that led to these findings. The following topics are discussed: The phagocytic activity of the reticulo-endothelial system. The pathogenesis of immune complex diseases. The impact of activated macrophages on tumor rejection. The evidence that T-cell immunity is specific for internal protein determinants generated by antigen processing. The maturation of the antibody response in terms of antibody affinity. The discovery of Ir gene control of specific immune responses and the role of MHC molecules as presenters of peptide antigens to T cells. The generation of alloreactivity. Lastly, he addresses the administration of science and, particularly, the problems related to the transfer of technology to industrial partners. PMID- 1910674 TI - A central role of perforin in cytolysis? AB - Studies on the gene structure, on the transcript, and on perforin protein are reviewed, including intracellular trafficking. Perforin transcription is tightly regulated and specific for CTL and NK. Two independent pathways for perforin induction exist, only one of them being IL-2 independent. Perforin expression in vitro and in vivo correlates with the functional expression of cytotoxicity in viral infection, transplant and tumor rejection, and in autoimmunity. Perforin together with granzymes is localized in cytolytic granules. However, the trafficking of those two proteins is quite different. Since the properties of perforin containing granules encompass the characteristics of secretory granules and of lyzosomes, the term granulosomes is used to describe this unique organelle. Evidence is reviewed to refute the concept that the homologous restriction factors of complement also restrict the lysis of homologous cells by perforin. PMID- 1910675 TI - The clinical use of colony stimulating factors. AB - Colony stimulating factors and interleukins regulate proliferation, differentiation, and functional activation of hematopoietic cells of multiple lineages. These hematopoietic growth factors are proving effective in vivo in stimulation of granulopoiesis in clinical situations associated with myelosuppression. G-CSF and GM-CSF promote accelerated granulocyte recovery following chemotherapy, or allogeneic or autologous bone marrow transplantation, in patients with cancer. In congenital defects of granulocyte production or in acquired disorders such as idiopathic neutropenia or aplastic anemia, CSF administration can lead to recovery of functioning granulocytes. This has resulted in a reduction in the morbidity and mortality associated with these diseases and now permits both a dose and a schedule intensification of chemotherapy. In myeloid leukemia and myelodysplastic syndromes, CSF treatment, particularly G-CSF, has proved effective for certain patients in improving neutrophil, platelet, and occasionally red cell production while reducing blast cells. The recombinant growth factors are generally well tolerated with few limiting toxicities at dose levels that effectively stimulate hematopoiesis. PMID- 1910676 TI - Memory B and T cells. AB - Three remarkable and unique features of the immune system are specificity, diversity, and memory. Immunological memory involves both T and B cells and results in a secondary antibody response that is faster, of higher affinity, and results in the secretion of non-IgM isotypes of Ig. In this review we discuss the properties of memory T and B cells, their specific receptors, and the events which occur both in the nucleus and on the cell surface during generation and activation of these cells. Although memory T and B cells use different mechanisms to elaborate memory, there are a number of interesting analogies: lymphokines vs antibodies and affinity maturation of B cell antigen receptors vs upregulation of adhesion molecules on T cells. Finally, we discuss the importance of these cells in health and disease and suggest what impact additional information about these cells might have on the manipulation of the immune response. PMID- 1910677 TI - Avian B-cell development: generation of an immunoglobulin repertoire by gene conversion. AB - The vertebrate B-cell repertoire is capable of generating up to 10(9) different antibody molecules using relatively few germline immunoglobulin (Ig) gene segments. To generate diversity, humans and mice depend on combinatorial and junctional variations that occur during the gene rearrangement events that produce complete heavy and light chain Ig genes. This gene rearrangement process goes on continuously in the bone marrow, where each developing B cell assembles a unique heavy and light chain Ig gene from families of functional V, D, and J gene segments. In contrast, chickens have only single functional V and J segments for the heavy and light chain loci, and chicken Ig gene rearrangement occurs only during a brief period of embryonic development. A specialized organ involved in avian B-cell development, the bursa of Fabricius, provides the microenvironment necessary for the amplification of B cells that have undergone productive Ig gene rearrangements. Within the bursa, B cells also acquire somatic diversity within the rearranged V gene segments of the heavy and light chain Ig loci. Somatic diversification of chicken V gene segments occurs by intrachromosomal gene conversion, a DNA recombination process which involves unidirectional transfer of nucleotide sequence blocks from families of V region pseudogenes into the functional rearranged VH and VL genes. PMID- 1910678 TI - Lpr and gld: single gene models of systemic autoimmunity and lymphoproliferative disease. AB - The autosomal recessive lpr and gld genes induce in mice multiple autoantibodies and the progressive accumulation of large numbers of non-malignant CD4- CD8- T lymphocytes. The clinical syndromes and immune abnormalities associated with these two nonallelic genes are nearly identical and are also highly dependent on background genes. MRL/lpr mice are particularly severely affected, and they develop a syndrome that is serologically and pathologically similar to human systemic lupus erythematosus (SLE). Abnormal cell marker expression in the aberrant lpr T lymphocytes includes surface antigens normally associated with activated T cells or even with B cells, and it occurs along with enhanced expression of certain oncogenes. The lpr gene results in intrinsic abnormalities of both T and B lymphocytes, yet its location and product are unknown. The gld gene is located on chromosome 1; its product is also unknown. Although many immunological abnormalities are known, the mechanism whereby these two genes induce autoimmunity and lymphoproliferation remains obscure. Further studies of mice bearing these mutant genes are certain to yield insights into systemic autoimmunity and the control of lymphocyte proliferation. PMID- 1910679 TI - The dendritic cell system and its role in immunogenicity. AB - Dendritic cells are a system of antigen presenting cells that function to initiate several immune responses such as the sensitization of MHC-restricted T cells, the rejection of organ transplants, and the formation of T-dependent antibodies. Dendritic cells are found in many nonlymphoid tissues but can migrate via the afferent lymph or the blood stream to the T-dependent areas of lymphoid organs. In skin, the immunostimulatory function of dendritic cells is enhanced by cytokines, especially GM-CSF. After foreign proteins are administered in situ, dendritic cells are a principal reservoir of immunogen. In vitro studies indicate that dendritic cells only process proteins for a short period of time, when the rate of synthesis of MHC products and content of acidic endocytic vesicles are high. Antigen processing is selectively dampened after a day in culture, but the capacity to stimulate responses to surface bound peptides and mitogens remains strong. Dendritic cells are motile, and efficiently cluster and activate T cells that are specific for stimuli on the cell surface. High levels of MHC class-I and -II products and several adhesins, such as ICAM-1 and LFA-3, likely contribute to these functions. Therefore dendritic cells are specialized to mediate several physiologic components of immunogenicity such as the acquisition of antigens in tissues, the migration to lymphoid organs, and the identification and activation of antigen-specific T cells. The function of these presenting cells in immunologic tolerance is just beginning to be studied. PMID- 1910680 TI - MHC class-I transgenic mice. AB - The introduction of cloned genes into the germline of mice has been proven to be a powerful tool to investigate the role of the respective gene products within the immune system. Here we summarize the transgenic mouse models that have been established with major histocompatibility complex (MHC) class-I genes. Foreign class-I alleles can be expressed in transgenic mice according to their normal expression patterns as authentic self molecules and can function in T-cell responses in the same way as endogenous class-I molecules. Since this is also true for most of the introduced human HLA class-I alleles, there is great interest in establishing mouse models for HLA-linked diseases. A new field of experimental approaches concerning self-tolerance has been opened by tissue specific expression of MHC antigens under specific promoters. Besides negative selection in the thymus, peripheral mechanisms could be identified that induce and maintain self-tolerance. PMID- 1910681 TI - The SCID mouse mutant: definition, characterization, and potential uses. AB - Mice homozygous for the scid mutation (scid mice) are severely deficient in functional B and T lymphocytes. The mutation appears to impair the recombination of antigen receptor genes and thereby causes an arrest in the early development of B and T lineage-committed cells; other hematopoietic cell types appear to develop and function normally. The arrest in lymphocyte development is not absolute; some young adult scid mice are "leaky" and generate a few clones of functional B and T cells. By 10-14 months of age, virtually all scid mice are leaky. Scid mice readily support normal lymphocyte differentiation and can be reconstituted with normal lymphocytes from other mice and even partially reconstituted with human lymphocytes. They also support the growth of allogeneic and xenogeneic tumors. Thus, scid mice are of interest for studies of both normal and abnormal lymphocyte development and function. In addition, they can be used to study the function of nonlymphoid cell types in the absence of lymphocytes. PMID- 1910682 TI - Maternally transmitted antigen of mice: a model transplantation antigen. AB - Molecular identification proved Mta, the maternally transmitted antigen of mice, to be a model minor histocompatibility (H) antigen. It consists of a peptide, MTF, that is presented on the cell surface by an H-2 class-I molecule, HMT. MTF is derived from ND1, a mitochondrially encoded protein, and the amino-terminal N formyl-methionine is essential for binding to HMT; conservative substitutions at the sixth residue causes MTF to be a minor H antigen. HMT is encoded by the M3 gene at the telomeric end of the H-2 complex. The peptide-binding site of HMT is hydrophobic, and allelic forms of the mature protein differ by only three amino acids. Homologues and analogues of the mouse Mta system have recently been identified in rats. PMID- 1910683 TI - Immunoglobulin gene transcription. AB - Transcriptional regulation of the immunoglobulin (Ig) genes is one of the best studied systems for understanding tissue-restricted gene control. Dissection of the Ig genes reveals that each contains multiple regulatory elements that are preferentially active in B lymphocytes. These include a promoter and one or more enhancer elements. Biochemical analysis and cloning of the genes for transactivator proteins has uncovered a variety of distinct proteins that are often members of gene families. The transactivators themselves are under complex regulation at the transcriptional level as well as by interactions with other proteins in the cell. It appears that the coordinate action of a select constellation of these transactivators conveys the information for tissue specific expression of the Ig genes. PMID- 1910684 TI - The SCID-hu mouse: a small animal model for HIV infection and pathogenesis. AB - The SCID-hu mouse is a heterochimeric small animal model designed to support hematopoietic differentiation and function in vivo. Multiple organs of the human hematolymphoid system have been successfully engrafted into the immunodeficient C.B-17 scid scid mouse, including fetal liver, thymus, lymph node, and skin. Co implantation of human fetal liver and human fetal thymus results in long-term, multilineage human hematopoiesis in vivo. Mature human lymphocytes within the SCID-hu mouse are phenotypically and functionally normal. HIV infection of the SCID-hu mouse reflects a tropism similar to that found in humans: only human organs with CD4+ cells are infected. Viral replication can thereafter be monitored with assays that are safe, reproducible, and quantitative. Given this small animal model, it is now possible to study systematically the infective process of HIV and to address questions about the efficacy of novel antiviral compounds or vaccines in vivo. PMID- 1910685 TI - Membrane cofactor protein (MCP or CD46): newest member of the regulators of complement activation gene cluster. AB - Membrane cofactor protein (MCP; CD46) is a widely distributed C3b/C4b-binding cell surface glycoprotein which serves as an inhibitor of complement activation on host cells. The protein has been purified, multiple cDNAs cloned and sequenced, and the genomic organization determined. MCP belongs to a family known as the regulators of complement activation (RCA) gene cluster. The RCA members are related structurally [possess approximately 60 amino acid repeating motifs termed short consensus repeats (SCR)], functionally (bind C3b/C4b), and genetically (genes are tightly clustered on chromosome 1 at q3.2). Beginning at its amino-terminus, MCP is composed of four SCRs, a ser/thr/pro-enriched region, an area of undefined function, a transmembrane hydrophobic domain, a cytoplasmic anchor and cytoplasmic tail. On SDS-PAGE, MCP migrates as two broad forms with Mrs of 59,000-68,000 and 51,000-58,000. The quantity of each form expressed is inherited in an autosomal codominant fashion. This structural heterogeneity is partly explained by the expression of multiple cDNA/protein isoforms that arise by alternative splicing of ser/thr/pro-rich exons (sites of heavy O glycosylation) and of cytoplasmic tails. This protein is of interest to immunologists and clinicians because of its role in regulation of the complement pathways and, therefore, inflammation in immune complex-mediated syndromes; to reproductive immunologists on account of its expression on sperm and at the maternal-fetal interface; and to tumor immunologists because of its high expression on malignant cells. The availability of monoclonal and polyclonal antibodies and molecular probes will be helpful in addressing questions about the biology of MCP in these and other areas. PMID- 1910686 TI - Fc receptors. AB - Recent advances in the structural analysis of the genes and proteins for immunoglobulin Fc domain receptors have provided a molecular characterization of this complex family. The wide cellular distribution of these receptors and their functional heterogeneity are reflected in the diversity of molecules which bind antibody and immune complexes. The detailed analysis of the IgG and IgE Fc receptors has indicated that these molecules have evolved from a common precursor through gene duplication. Similarities among these receptors, in both structure and function have emerged. Thus, the Fc receptors provide an example of a class of molecules in which conserved domains are combined with divergent sequences to yield a diversity of function. PMID- 1910687 TI - MHC class-II molecules and autoimmunity. AB - Molecular and genetic studies of HLA class-II genes provide new insights into the basis for MHC associations with autoimmunity. Polymorphisms among class-II genes identify specific haplotypes associated with autoimmune diseases such as type-I diabetes, rheumatoid arthritis, celiac disease, and pemphigus vulgaris. In some cases, single genes within those haplotypes are themselves implicated in disease susceptibility. Interactions, both cis and trans, between candidate susceptibility genes suggest a number of possible mechanisms critical for autoimmune triggering events involving class-II molecules. Amino acid sequence comparisons between products of candidate susceptibility genes and other class-II genes pinpoint a limited number of critical sites within HLA molecules which appear to be responsible for pathogenic events. PMID- 1910688 TI - Interactions between immunogenic peptides and MHC proteins. AB - The MHC class-I and class-II molecules are highly polymorphic membrane proteins, which bind and transport to the surface of cells peptide fragments of intact proteins. The peptide-MHC complexes are recognized by the antigen-specific receptor of T lymphocytes and are the basis by which the cellular immune system distinguishes self from nonself. In order to perform this function, MHC proteins simultaneously display a large spectrum of structurally divergent peptides for a sufficiently long period of time for the T cell repertoire to scan the cell effectively. Consistent with the protein's biological role, the rates of association and dissociation at physiological pH are very slow relative to other known receptor-ligand interactions. The mechanism by which the proteins do this is still poorly understood, but recent experimental results indicate that the rate determining step may be a conformational change that results in the entrapment of the peptide. A variety of binding assays have been developed that allow study of the detailed kinetics and specificity of the interaction. The optimal peptide length for binding is between 8 and 12 amino acids with the central 5-7 residues contributing the majority of the specific contacts. Determining the conformation of bound peptides has been hampered by the inherent ability of the receptor to bind manifold sequences. Consequently, strategies employing monosubstituted analogs have had only limited success. Approaches using biotinylated amino acids and other bulky substituents or multiple substitutions have generated more information. Recent experiments demonstrating that peptides with polyalanine, polyproline, or polyglycine bind well to MHC proteins have proven that the structural requirements for binding are quite minimal. In fact, a significant factor of the selectivity for binding appears to be the avoidance of deleterious contacts, rather than the need for a large number of critical interactions. Binding experiments also have shown that several peptides can bind a large number of MHC class-I and class-II alleles. The degenerate binding indicated that the binding site of MHC proteins must have a significant number of conserved features. Solution of the crystal structures of the MHC class-I alleles A2 and Aw68 has identified a putative antigen-combining site whose overall dimensions were quite similar between the two structures. The detailed surface topology of the site varied between the two alleles due to the size and chemical properties of the side chains of the polymorphic amino acids composing the cleft.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1910689 TI - T-cell differentiation is influenced by thymic microenvironments. AB - Intrathymic T-cell differentiation requires a symbiotic interaction between thymic microenvironments and developing T cells. This paper attempts to provide insight into lympho-stromal interaction and reviews the architecture of thymic microenvironments, the phenotype of thymic microenvironments, the in vitro culture of thymic microenvironments, and the supportive role of thymic microenvironments in T-cell differentiation. Moreover, we discuss experimental manipulation of thymic microenvironments in vivo and in vitro, using monoclonal antibodies directed to cell surface determinants on stromal cells or their ligands on lymphoid cells. Finally, new types of experimental mouse models are considered with special reference to the role of thymic microenvironments in positive and negative selection of the T-cell repertoire, and the potential influence of T cells on the development of thymic microenvironments. PMID- 1910690 TI - Properties of the novel proinflammatory supergene "intercrine" cytokine family. AB - A family consisting of at least ten distinct novel 8-10 kd cytokines has been identified over the past 12 years. These cytokines exhibit from 20 to 45% homology in amino acid sequence, are probably all basic heparin-binding polypeptides, and have proinflammatory and reparative activities. The cDNA for these cytokines are characterized by conserved single open reading frames, typical signal sequences in the 5' region, and AT rich sequences in the 3' untranslated regions. Those human cytokines known as interleukin 8, platelet factor 4, beta thromboglobulin, IP-10 and melanoma growth stimulating factor or GRO can be assigned to a subfamily based on their location on chromosome 4 and unique structural features, whereas the second subset consisting of LD78, ACT-2, I-309, RANTES, and macrophage chemotactic and activating factor (MCAF) are all closely linked on human chromosome 17. In this review we have summarized and discussed the available information concerning the regulation and structure of the genes, the structure and biochemical properties of the polypeptide products, their receptors, signal transduction, cell sources, and in vitro as well as in vivo activities of these cytokines. PMID- 1910691 TI - The CD4-gp120 interaction and AIDS pathogenesis. AB - Infection by the human immunodeficiency virus (HIV) leads to progressive destruction of the CD4+ subset of T lymphocytes, resulting in immunodeficiency and AIDS. The selectivity of CD4+ cell destruction is due to the specific binding of gp120, the external envelope glycoprotein of HIV, to CD4, initiating viral entry. Binding of gp120 to CD4 on the cell surface may also lead to CD4+ cell depletion by inappropriate immune targeting, and may interfere with CD4+ cell function and ontogeny by disrupting CD4-mediated cell signaling. The CD4-gp120 interaction is thus an obvious target for AIDS therapeutics. PMID- 1910692 TI - The cell biology of antigen processing and presentation. AB - Histocompatibility molecules are peptide-binding proteins and present antigenic peptides to T cells. In spite of similarity in structure and peptide specificity, class-I and class-II histocompatibility molecules present peptides at different intracellular locations. Class-I molecules present peptides derived from endogenous proteins, but class-II molecules can present peptides from endocytosed (exogenous) antigen as well as endogenous antigen. Binding of antigenic peptides by histocompatibility molecules is a function of their assembly, intracellular trafficking, and endocytosis. For class-I molecules, assembly appears to be the most important step for peptide acquisition, while all three processes can potentially influence class-II antigen presentation. The versatility of peptide binding by class-II MHC molecules is due to its association with the invariant chain which blocks peptide binding during the initial stages of class-II assembly and export and contributes to the endosomal targeting of class-II molecules. Once invariant chain dissociates, class-II molecules become competent to bind peptides and are released to the cell surface. The location in which a particular antigenic peptide is produced is a function both of its route of introduction into the cell and its susceptibility to degradation. These factors contribute significantly to whether an antigen will be presented by class-I or class-II molecules and should be taken into account in the design and development of vaccines. PMID- 1910693 TI - Regulation of human B-cell activation and adhesion. AB - Human B lymphocyte differentiation is regulated by signals transmitted after binding of cytokines to their specific receptors and/or cross-linking of cell cell adhesion receptors. In addition to surface immunoglobulin (sIg) receptors for antigen, a number of B cell-associated surface molecules have now been identified which may regulate activation and adhesion of B cells. These include members of the Ig supergene family such as CD19, CD22, B7/BB1, and BMC1, cell surface enzymes such as CD10, CD73, and CDw75, and proteins with multiple transmembrane domains such as CD20 and CD37. In this review we describe how several of these accessory molecules may affect signaling via antigen receptors and influence primary vs secondary immune responses. For instance, signaling via either CD21 or CD22 can augment responses to anti-Ig; the B cell activation marker B7/BB1 may function to trigger T cells via its ligand, CD28, to produce cytokines which in turn stimulate B cells; and the receptor, CD40, may transmit a signal to protect germinal center B cells from undergoing programmed cell death. Understanding how B cell accessory molecules regulate key interconnections during development may provide insights into the control and management of diseases with B-cell dysfunctions. PMID- 1910694 TI - Mandibular reconstruction with a recombinant bone-inducing factor. Functional, histologic, and biomechanical evaluation. AB - Bone morphogenetic protein-2 (BMP-2) is a human recombinant bone-inducing factor that stimulates bone formation within 14 days. Twenty-six dogs underwent reconstruction of 3-cm full-thickness mandibular defects. After stabilizing the defects with stainless steel reconstruction plates, test implants composed of inactive dog bone matrix carrier and human recombinant BMP-2 were placed in defects of 12 animals (group 1). Control implants (carrier without BMP-2) were used in 10 animals (group 2), and no implants were placed in mandibular defects of four animals (group 3). Animals were killed at 3 and 6 months. The reconstructed segments were evaluated by roentgenography, analysis of functional stability, histology, histomorphometry, and analysis of biomechanical strength using three-point bend testing. In group 1, reconstruction plates were removed at 10 weeks because stiff, noncompressible mineralized bone formed across the defects, allowing the animals to chew a solid diet. The defects from groups 2 and 3 showed minimal, if any, bone formation and remained grossly unstable, prohibiting plate removal or advancement to a solid diet. Histomorphometric analysis at 6 months revealed that 68% of the group 1 implants were replaced by mineralized bone, whereas mineralized bone occupied less than 4% of the implants in groups 2 and 3. Biomechanical testing at 6 months revealed that the average bending strength of the reconstructed hemimandibles (expressed as a percentage of the contralateral hemimandible) was 27% for group 1 and 0% for group 2. The biomechanical strength of the defects reconstructed with BMP-2 increased significantly from 3 to 6 months and was related to degree of mineralization and thickness of bone bridging the defect. PMID- 1910695 TI - Muscle transfer for laryngeal paralysis. Restoration of inspiratory vocal cord abduction by phrenic-omohyoid transfer. AB - Omohyoid muscle transfer to the denervated posterior cricoarytenoid muscle (PCA) was performed in three monkeys. The transposed omohyoid muscle was reinnervated by the phrenic nerve by performing nerve anastomosis prior to muscle transfer. The muscles were sutured over the denervated ipsilateral PCA muscle to allow for neurotization of the denervated PCA muscle in such a way as to reproduce the directional vector of PCA contraction, eg, to mimic the directional pull of the PCA muscle. The muscle flaps were found to be long enough to reach the contralateral PCA muscle, confirming that the technique might be used ultimately for bilateral simultaneous PCA reinnervation. Each animal achieved reinnervation. The superiorly based omohyoid muscle flap was found to more closely emulate the size and orientation of the underlying PCA muscle. Electromyography, videolaryngoscopy, and histologic examination were used to confirm the results. The procedure has the potential for PCA muscle replacement in long-standing cases of paralysis with PCA denervation atrophy as well as for reinnervating a denervated PCA muscle. PMID- 1910696 TI - Congenital interarytenoid web. AB - Congenital interarytenoid web is a rare laryngeal anomaly whose distinctive feature is a band of tissue joining the medial surfaces of the arytenoids and restricting abduction of the vocal cords. It appears to arise from persistence of the embryonic membranous interarytenoid layers, which form the epithelial lamina of the fetal laryngeal sagittal cleft. This review of 16 cases seen in a 15-year period describes the clinical features, diagnostic evaluation, and management. In addition to the interarytenoid web, which is present to some degree in all patients, associated anomalous features may include subglottic stenosis, enlarged bulky arytenoids, and difficulty exposing the larynx and maintaining the airway during anesthesia and endoscopy. The association of these four features in this rare laryngeal anomaly has not been previously described. Diagnosis depends on direct laryngoscopy with particular attention to the posterior larynx. Tracheotomy may be required for 3 to 5 years as definitive corrective management has not been established. PMID- 1910697 TI - The prevention of postoperative stridor and laryngospasm with topical lidocaine. AB - Tonsillectomy and adenoidectomy can predispose to stridor and laryngospasm in the immediate postextubation period. A prospectively randomized study of 133 patients undergoing tonsillectomy and adenoidectomy was undertaken to determine if the topical application of 4 mg/kg of 4% lidocaine at the time of intubation would decrease the incidence of postoperative stridor and laryngospasm. Taken together, eight (12%) of 67 control patients suffered stridor or laryngospasm vs two (3%) of 66 patients receiving lidocaine. It is concluded that lidocaine administered topically at the time of intubation for adenotonsillectomy helps prevent postoperative stridor and laryngospasm. Surgery of the upper aerodigestive tract often involves not only the technical aspects of the surgical procedure but also concomitant management of the airway. This can present a challenge to even the most adept otolaryngologist and anesthesiologist. Accidental extubation is always possible, and reintubation can be difficult in the presence of blood and saliva. The difficulty is often compounded with a patient who is not completely paralyzed. PMID- 1910698 TI - The latissimus dorsi donor site. Current use in head and neck reconstruction. AB - Reconstruction of head and neck defects after trauma, tumor extirpation, or disease has improved with the modern development of multiple donor sites. However, the selection of a particular pedicled or free flap should balance the required sophistication of repair with donor site morbidity. The latissimus dorsi donor site is capable of providing a versatile group of tissues; ie, muscle, skin, subcutaneous tissue, bone, nerve, and vascular pedicle. We present a series of 30 latissimus dorsi flaps (20 pedicled and 10 free) used for craniotemporal, craniofacial, midfacial, oral, oropharyngeal, mandibular, and neck skin reconstructions. The flap survival rate was 90%, a result similar to other large series. The indications for using the latissimus dorsi as opposed to other donor sites were large skin defects, cephalad defects, total glossectomy defects, defects requiring free tissue transfer, and defects where other regional donor tissue was unavailable. We also present a novel flap design for total glossectomy reconstruction. PMID- 1910699 TI - Irradiation. A significant risk factor for carotid atherosclerosis. AB - Radiation exacerbates the development of atherosclerosis in the large arteries of animals and is postulated to do likewise in human beings. To study this relationship, we used high-resolution B-mode ultrasonography to measure carotid artery wall thickness in 29 previously irradiated head and neck cancer patients and compared the results with those of nine epidemiologically similar but nonirradiated head and neck cancer patients. Maximal intima-media thickness was greater in the study group (mean, 1.28 +/- SE 0.06 mm) than in the control group (mean, 0.90 +/- SE 0.05 mm). Even after the effects of age, hypertension, and tobacco consumption were controlled, these differences remained statistically significant. This study suggests that irradiation may contribute to the development of more severe and extensive carotid atherosclerosis in head and neck cancer patients who receive radiation therapy. PMID- 1910700 TI - Significance of abnormal indium In 111-labeled leukocyte accumulation in the head and neck region. AB - The localization of occult infection is often a difficult clinical problem. In 1975, labeling of leukocytes with indium In 111 became technically feasible, and subsequent clinical experience with 111In-labeled leukocyte scanning demonstrated high sensitivity and specificity for acute infection. To our knowledge, experience with white blood cell scanning in the head and neck has not been previously reported. The University of California, San Francisco, experience with 111In-labeled white blood cell scanning was reviewed. Between 1982 and 1987, 520 whole-body 111In-labeled leukocyte studies were performed, of which 60% were interpreted as abnormal. Eighteen studies were abnormal in the head and neck region, and the medical records of these patients were retrospectively reviewed. Abnormal findings correlated with other evidence of disease that involved mucosal surfaces, the neck, and the mediastinum. Sites in the nasopharynx with nasogastric tubes and tracheotomy sites were abnormal without associated clinical evidence of infection. Further clinical experience is needed to correlate white blood cell scan findings with disease in the head and neck and to define the role of the scan in diagnosis and management of otolaryngological disorders. PMID- 1910701 TI - A basic model to study acoustic evaluation of airway obstruction. AB - Listening to a human airway to determine obstruction is a highly subjective art and an important clinical tool. Sophisticated acoustic monitoring techniques should be developed and tested in the laboratory before they are applied in the clinic. We describe construction of an acoustic tube model to study the mechanism of noise generation in a simulated obstructed human airway. Spectral differences were demonstrated between different amounts and locations of obstruction and changes resulting from variations in airflow using Fast-Fourier transform techniques. With this analog model, systematic research can be conducted to define expected patterns in obstructed human airways for use in the clinical setting. PMID- 1910702 TI - Cochleosacculotomy revisited. Long-term results poorer than expected. AB - Cochleosacculotomy has been described as a simple, efficacious treatment for relief of vertigo in patients with Meniere's disease in whom medical therapy has failed. We reviewed records of 11 elderly patients with good vestibular function who were thought to be ideal candidates for this procedure. Average follow-up was 17 months. Contrary to previous reports, long-term control of vertigo was poor, and more than 80% of the patients suffered a significant hearing loss from this procedure. Four of 11 patients required a second surgical procedure to control their vertigo. Audiometric measures revealed statistically significant postoperative increases in puretone thresholds at all frequencies and speech reception threshold, and a decrease in discrimination scores. Based on the results of this study, we no longer plan to use cochleosacculotomy for the treatment of elderly patients with Meniere's disease. PMID- 1910703 TI - Auditory monitoring during acoustic neuroma removal. AB - Preservation of hearing has become attainable for patients with small acoustic neuromas. Brain-stem auditory evoked response was monitored intraoperatively in 60 patients undergoing acoustic neuroma surgery via the posterior fossa approach. The overall rate of hearing preservation was 30% in the monitored group and 20% in 60 patients who were matched for tumor size and preoperative hearing level and underwent the same surgical procedure but without intraoperative brain-stem auditory evoked response monitoring. The rate of hearing preservation was correlated with tumor size: with tumors less than or equal to 1 cm, hearing was preserved in 82% of monitored and 36% of unmonitored patients; hearing was not preserved with tumors larger than 3 cm. Intraoperative brain-stem auditory evoked response monitoring appears to have improved the preservation of hearing during removal of small tumors. PMID- 1910704 TI - Three-dimensional reconstruction of temporal bone from computed tomographic scans on a personal computer. AB - The advantages of computer reconstruction of anatomical structures from computed tomographic scans are common knowledge by now. Unfortunately, to date most reconstructions have required the use of large computers and/or have entailed tedious manual contour tracing. The system described here allows largely automatic detection of surfaces in computed tomographic scans plus the usual display capabilities including feature selection, magnification, rotation, shading, and slicing as well as measurement of lengths and angles. It runs on a normal International Business Machines AT-compatible computer with a medium resolution video card. PMID- 1910705 TI - Quinine-induced tinnitus in rats. AB - Quinine ingestion reportedly induces tinnitus in humans. To expand our salicylate based animal model of tinnitus, a series of conditioned suppression experiments was performed on 54 male-pigmented rats using quinine injections to induce tinnitus. Quinine induced changes in both the extent of suppression and recovery of licking, which followed a pattern that paralleled those produced after salicylate injections, and which may be interpreted as the result of tinnitus perception in animals. These changes depended on the dose and time schedule of quinine administration. Additionally, the calcium channel blocker, nimodipine, abolished the quinine-induced effect in a dose-dependent manner. PMID- 1910706 TI - Objective low-frequency audiometry by distortion-product acoustic emissions. AB - The aim of this study was to measure distortion-product otoacoustic emissions (DPOEs) in a clinical setting. First, DPOE input-output functions were automatically realized to determine the ratio of the pure tones (primaries) f2 and f1 that would elicit the most significant DPOE input-output function. The DPOE input-output functions presented two separate portions for the f2/f1 ratio, ranging from 1.18 to 1.26: (1) below 60-dB sound pressure level (SPL), a saturating portion with a DPOE detection threshold at 36-dB SPL; and (2) above 66 dB SPL, a linear portion. For other f2/f1 ratios, DPOE input-output functions had a more linear behavior. The DPOEs generated by primary intensities below 60-dB SPL, which show saturating behavior, probably have their origin in the properties of outer hair cells. This indicates that DPOE measurements in a clinical setting must be realized with precise stimulus values: (1) f2/f1 ratio near 1.22, and (2) primary intensities below 60-dB SPL. Second, DPOE input-output functions were realized for DPOEs varying from 707.5 to 342 Hz. No more saturating plateau could be observed with DPOEs below 512.5 Hz, suggesting that active mechanisms are absent below 725 Hz within the human cochlea. These data permit us to establish the bases of an objective low-frequency audiometric test. PMID- 1910707 TI - Biostatistics in otolaryngology journals. AB - Clinical research depends on biostatistics to form meaningful inferences from uncertain data. We performed a cross-sectional analysis of clinical research in otolaryngology journals to identify trends in statistical usage and determine the statistical aptitude expected of journal readers. Statistical content and study design were assessed for 1262 articles from 1969, 1979, and 1989. General trends toward an increasing use of inferential statistics and stronger study designs were observed. The number of analytic and experimental studies employing inferential statistics has risen from 20 (31%) in 1969 to 145 (65%) in 1989. Although familiarity with only five statistical techniques gave access to 90% of current articles, this study suggests that the level of statistical expertise demanded of both researchers and readers will continue to increase. PMID- 1910708 TI - Effects of pharmacologic agents on human keloids implanted in athymic mice. A pilot study. AB - The treatment of keloids remains difficult. In experimental studies, lathyrogenic agents and colchicine have been shown to be effective in keloid prevention. Recently, a study was published of a new animal model utilizing human keloids implanted in athymic mice. We used the same model to compare the effects of penicillamine, acetylcysteine, colchicine, and triamcinolone acetonide. Unexpectedly, all keloids implanted showed a growth peak at 4 weeks and then regression in size. Histologic sections of the implanted keloids revealed peripheral vascularity, collagen bundles similar to the parent keloids, and no evidence of implant rejection. After 8 weeks, the mice treated with the lathyrogenic agents exhibited a higher rate of regression when compared with the control mice. While triamcinolone acetonide may have prevented keloid implant growth, drug toxic reaction may have been a factor. PMID- 1910709 TI - Intravascular papillary endothelial hyperplasia in the maxillary sinus. A benign lesion that may be mistaken for angiosarcoma. AB - Intravascular papillary endothelial hyperplasia is a vascular benign lesion bearing some similarities to malignant angiosarcoma. To the best of our knowledge, it has never been described within the paranasal sinuses. A case of such a lesion within the maxillary sinus appearing in a 17-year-old boy who presented with unilateral facial pains and proptosis is reported. The lesion, despite its benign nature, extended to the ethmoidal cells and nasal cavity and pressed the floor of the orbit. Clinically and histopathologically it may be mistaken for an angiosarcoma. An awareness of this similarity and the features in which it differs from angiosarcoma will prevent incorrect diagnosis and inappropriate treatment. PMID- 1910710 TI - The role of surgery in rhabdomyosarcoma of the head and neck in children. AB - The role of surgery in the treatment of rhabdomyosarcoma of the head and neck has diminished during the past 25 years. Treatment of this tumor in the pediatric population has involved radical radiation therapy and chemotherapy with little or no role for surgery. However, the potential effect of irradiation on facial growth and the appearance of secondary irradiation-induced tumors has raised the question as to whether surgery may once again play a role in the treatment of these patients. Advances in skull base and reconstructive surgery and microsurgical techniques have permitted a reconsideration of initial ablative surgery. The head and neck surgical team must be prepared to respond in those patients in whom craniofacial development is at risk or recurrence has occurred after radical chemotherapy and/or radiation therapy. PMID- 1910711 TI - The ethics of injected collagen. PMID- 1910712 TI - The ethics of collagen injections--a rebuttal. PMID- 1910713 TI - Nodular fasciitis of the head and neck in children. A deceptive lesion. AB - Nodular fasciitis represents a discrete, benign, presumably reactive proliferation of fibroblasts. However, its rapid rate of growth and a sarcomatous histologic appearance are often deceptive. Multiple pathologic reviews are frequently conducted in an attempt to distinguish nodular fasciitis from other lesions. Such confusion is especially problematic in the pediatric otolaryngic population in which nodular fasciitis is not commonly encountered and mesenchymal malignancies of the head and neck are of fundamental concern. Between 1976 and 1988, 12 cases of nodular fasciitis were diagnosed at the Children's Hospital of Philadelphia (Pa). Six children presented with head and neck lesions and ranged from 6 to 13 years of age. The clinical and histopathologic features of these cases are reviewed. PMID- 1910714 TI - Discontinuous vs in-continuity neck dissection in carcinoma of the oral cavity. AB - We compared the results of transoral excision of the primary tumor with discontinuous neck dissection with the results of in-continuity dissection of primary tumor and neck nodes in anteriorly localized squamous cell carcinoma of the oral cavity. We analyzed 27 patients who underwent 28 discontinuous dissections and 34 patients who underwent 40 in-continuity dissections for T2 anterior tongue or floor-of-mouth carcinoma. The overall ipsilateral neck recurrence rate was 11%. The discontinuous dissection group did significantly worse than the in-continuity dissection group, with a neck recurrence rate of 19%. Consequently, the actuarial 5-year survival of patients who underwent a discontinuous dissection was substantially decreased (63%) compared with patients who were treated by an in-continuity dissection (80%). Discontinuous neck dissection, thus, is not to be recommended in oral cancer. PMID- 1910715 TI - Langerhans cells related to prognosis in patients with laryngeal carcinoma. AB - Intratumoral and peritumoral infiltration of T-zone histiocytes, mainly of mature Langerhans cells, was investigated in 88 patients with squamous cell carcinoma of the larynx by immunohistochemical methods using polyclonal antibodies against S100 protein and lysozyme. Granulocytic and lymphoid inflammatory infiltration and its relationship to the presence of Langerhans cells were also evaluated. Langerhans cells were present within the cancer tissues and showed a relationship with lymphoid infiltrate. No significant correlation was present among the density of Langerhans cells and the site of neoplastic growth (supraglottic or subglottic), granulocytic inflammatory infiltration, histological tumor grade, or clinical stage. Patients with high or intermediate density of Langerhans cells survived longer than those with low density (mean survival, 61%, 62%, and 0%, respectively). The number of Langerhans cells was relevant in patients with evident infiltration of lymphocytes and plasma cells, according to their ability to present antigens to sensitized T cells. Our results indicate that the presence of high or intermediate density of Langerhans cells and of marked lymphoid inflammation may be considered favorable prognostic factors for patients with squamous cell carcinoma of the larynx. PMID- 1910717 TI - Vocal fold epithelial hyperplasia. Vibratory behavior vs extent of lesion. AB - The vibratory behavior of 72 vocal folds with epithelial hyperplasia or dysplasia was investigated by means of videostroboscopy. The amplitude of vibration (AMP) and mucosal wave (WAV) were related to the relative area, depth, and relative volume of the lesion. The AMP and WAV were evaluated for the entire vocal fold (AMPE, WAVE) and for the affected portion or the lesion (AMPL, WAVL). The AMPE, AMPL, WAVE, and WAVL were negatively related to the relative area, depth, and relative volume. The relationship between the limited vibratory movement and the extent of the lesion was most significantly manifested in WAVL. A complete absence of any vibratory movement of the vocal fold took place only for large lesions occupying three fourths or more of the membranous vocal fold. PMID- 1910716 TI - Effective head and neck tumor markers. The continuing quest. AB - To evaluate the clinical value of two serologic tumor markers, squamous cell carcinoma-associated antigen and plasma lipid-bound sialic acid, for identifying cancers of the head and neck, plasma specimens were obtained from patients receiving care for untreated newly diagnosed cancers of the head and neck, routine surveillance for recurrence, or treatment for chronic nonmalignant otolaryngologic conditions. Using identical methods at two institutions, levels of both markers were determined blind to diagnoses for patients with biopsy proven cancers of the head and neck (n = 134) and for those defined as cancer free based on clinical evaluation for 6 months (n = 140). Disease status was determined blind to tumor marker level results. Cancer prevalence was 48.9%. Applying standard normal limits used alone, plasma lipid-bound sialic acid test sensitivity was 63.4% and specificity was 77.9%. For squamous cell carcinoma associated antigen alone, test sensitivity was 27.6% and specificity was 85.0%. Neither test alone appears sensitive enough to effectively detect early cancers of the head and neck. When the results of both tests in series combination were positive, sensitivity was 18.7% and specificity was 95.0%. If either was positive in parallel combination, sensitivity was 72.4% and specificity was 68.0%. Further evaluation is required that applies different definitions of normal and determines longitudinal changes with disease status. PMID- 1910718 TI - Posterior cricoarytenoid muscle denervation. AB - Vocal fold paralysis most commonly results from injury to the recurrent laryngeal nerve. The length of time required for denervation atrophy would be useful in planning reinnervation procedures. Given the absence of long-term data on the status of the canine posterior cricoarytenoid muscle following denervation, this study was undertaken. The results indicate that muscle atrophy does not occur for at least 1 year following denervation. PMID- 1910720 TI - The rectus abdominis free flap in head and neck reconstruction. PMID- 1910719 TI - Language screening as a factor in the management of the pediatric otolaryngic patient. Effectiveness and efficiency. AB - The Early Language Milestone Scale, a screening test for language in children from birth to 36 months of age, was applied to the total population of pediatric otolaryngic patients. Ninety-seven percent of the patients were found to have a completed screen. Thirty percent of the patients failed one or more portions of the Early Language Milestone screen. Practice management was modified by the results of the Early Language Milestone in all the patients who failed the screen. The Early Language Milestone was found to be efficient and effective in contributing to the management of the children with pediatric otolaryngic disorders and diseases. PMID- 1910722 TI - Rapid intraoperative tissue expansion for closure of facial defects. AB - Rapid intraoperative tissue expansion (RITE) has been shown to have definite applicability to reconstruction in the head and neck. However, widespread use of this modality has yet to be adopted by the otolaryngologic community. Believing that RITE might offer some advantages in the reconstruction of soft-tissue facial defects following Mohs micrographic surgery for cutaneous malignant neoplasms, we evaluated 30 consecutive patients referred for cosmetic reconstruction after Mohs micrographic surgery for the use of RITE. Eight patients were selected and underwent reconstruction using a total of 10 tissue expanders. Herein, we describe our experience with this initial series as well as some background and future applications of RITE. PMID- 1910723 TI - Angioedema after long-term use of angiotensin-converting enzyme inhibitor. PMID- 1910721 TI - Autosomal dominant sensorineural hearing loss. Pedigrees, audiologic findings, and temporal bone findings in two kindreds. AB - We report the clinical and otopathologic findings in three persons from two kindreds affected with adult-onset autosomal dominant progressive sensorineural hearing loss. The primary pathologic change is a deposit of acid polymucosaccharide ground substance in the cribrose areas; in the spiral ligament, limbus, and spinal lamina of the cochlea; and in the stroma of the maculae and cristae. These deposits obstruct the channels that accommodate the dendritic nerve fibers to the auditory and vestibular sense organs. The end result is strangulation and degeneration of dendrites followed by retrograde neuronal degeneration in association with varying degrees of atrophic change in the sense organs. PMID- 1910724 TI - Computed tomography of nasolacrimal duct obstruction after endoscopic sinus surgery. PMID- 1910725 TI - Acoustic neuromas. Some are slow growth or no growth. PMID- 1910726 TI - Meatoplasty for endaural approach. PMID- 1910727 TI - Head and neck burns. Evaluation and current management. AB - More than half of the 150,000 burn patients hospitalized in the United States each year have head and neck involvement, with 3% to 7% sustaining concomitant inhalation injury. With advances in fluid replacement therapy and specialized burn care units, mortality has fallen from near 100% to 24% for burns of 75% to 90% of body surface area. The most common causes of death are respiratory complications and sepsis. Inhalation injuries can be diagnosed by laryngoscopy, and compromised airways can then be intubated (with tracheotomy for long-term management) and sloughing mucosa and inspissated mucus removed by serial bronchoscopy. Sepsis is minimized by early excision of burn eschar and autografting or, in the widely burned, temporary coverage with cadaver allograft, porcine xerograft, or skin substitutes until successive crops of autografts are available. The head and neck presents substantial reconstructive and rehabilitative challenges, which must be addressed in aesthetic units. PMID- 1910728 TI - Interaction of cocaine with nasal mucosa. AB - Canine nasal mucosa was studied in vitro to examine (1) the production of vasoconstriction by cocaine and, (2) the epithelial permeability of cocaine. Cocaine, by itself, failed to induce any contraction of the nasal blood vessels but did enhance contractions resulting from electrical stimulation or addition of norepinephrine. Results indicate that cocaine produces vasoconstriction by blocking the reuptake of endogenous norepinephrine rather than any direct action on vascular smooth muscle. Cocaine was found to be three times more permeable than sucrose, which has a similar molecular weight. The transepithelial permeability of cocaine was independent of direction and did not display competition. Results indicate that cocaine permeates by simple diffusion and that the relatively high permeability is due to a greater lipid solubility. Cocaine was found to accumulate in the nasal mucosa. A significant portion of the accumulation is associated with specific sites that are characteristic of catecholamine uptake sites. PMID- 1910729 TI - Microbiology of chronic sinusitis in children. AB - To better understand the factors involved in chronic sinusitis in childhood, we cultured the sinuses, middle meatus, and nasopharynx in 39 children requiring surgical intervention. Sixty-nine percent of these patients had other medical problems, including asthma (49%) and immunologic compromise (18%). We cultured coagulase-negative staphylococcus in 18 patients, Streptococcus viridans in 14 patients, normal flora in 10 patients, Staphylococcus aureus in nine patients, group D streptococcus in five patients, Corynebacterium in five patients, Haemophilus influenzae in three patients, Neisseria in three patients, and Streptococcus pneumoniae, group A streptococcus, Escherichia coli, Pseudomonas aeruginosa, Klebsiella oxytoca, Propionibacterium acnes, Actinomyces, and an anaerobic gram-negative bacillus in one patient each. Cultures yielded no growth in nine patients. A strong association between cultures of the middle meatus obtained ipsilaterally and cultures of the maxillary (83%) and ethmoid sinuses (80%) occurred. A poor correlation was found between cultures of the nasopharynx and maxillary (45%) and ethmoid sinuses (49%). All seven patients who had both maxillary and ethmoid sinus cultures showed the same organisms in both sinuses. Only 41% of organisms were found on both sides when procedures were performed bilaterally. Cultures of the middle meatus appear to be sensitive and specific for organisms within sinuses. The presence of predominantly nonvirulent organisms in low titers suggests that additional factors other than bacterial overgrowth contribute to the pathogenesis of chronic sinusitis in children. PMID- 1910730 TI - Steroids and rhinoplasty. A double-blind study. AB - Many facial plastic surgeons use perioperative steroids to reduce postoperative edema and morbidity. This use of steroids is based more on theory and anecdotal experience than on controlled studies. We studied 49 patients undergoing rhinoplasty in a randomized, double-blind fashion to evaluate the effects of perioperative and postoperative steroid use. We found significantly less postoperative eyelid and paranasal edema in those patients receiving steroids. In addition, trends toward less ecchymosis, less intranasal edema, and less discomfort in the patients receiving steroids were noted. PMID- 1910731 TI - Preexcision blepharoplasty. AB - Numerous techniques have been described for lower lid blepharoplasty. Over the past 15 years, a preexcision (pinch) technique with preservation of the pretarsal orbicularis oculi muscle has been used in more than 1000 cases presenting with dermatochalasis and pseudoherniated fat without lateral skin redundancy. The amount of lower lid skin to be excised is estimated by pinching the skin. Preservation of the pretarsal orbicularis oculi muscle adds support to the tarsoligamentous complex. This technique aids in preventing the development of both postoperative ectropion and rounding of the lower lid. Technical considerations of the preexcision (pinch) technique and a description of alternative techniques are outlined. Indications, complications, and patient satisfaction are discussed. PMID- 1910732 TI - Signals, mechanisms, and function of the acute lipid response to sepsis. PMID- 1910733 TI - [Application of nuclear magnetic resonance for the determination of the structure of proteins in solution]. AB - Knowledge of three-dimensional structure is a key factor in protein engineering. It is useful, for example, in predicting and understanding the functional consequences of specific substitution of one or more amino acids of the polypeptide chain. It is also necessary for the design of new effectors or analogs of the substrates of enzymes and receptors. X-ray diffraction by crystals of the biomolecule was for a long time the only method of determining three dimensional structures. In the last 5 years, it has been joined by a new technique, two-dimensional nuclear magnetic resonance (2D NMR), which can resolve the structure of middle-sized proteins (less than 10 kilodaltons). The technique is applied on solutions whose pH, ionic strength, and temperature can be chosen and changed. The two basic measurements, COSY and NOESY, detect respectively the systems of hydrogen nuclei, or protons, coupled through covalent bonds, and those in which the interproton distances are less than 0.5 nm. A systematic strategy leads from resonance assignments of the two-dimensional spectrum to molecular modeling with constraints and finally to the determination of the molecular structure in the solution. Much sophistication is needed even today for the first task, the assignment of the resonances. Each of the COSY and NOESY spectra is a two-dimensional map, where the diagonal line is the one-dimensional spectrum, and the off-diagonal peaks indicate connectives between protons. Peak assignment to a specific type of amino acid is based on the pattern of scalar couplings observed in the COSY spectrum. Next, the amino acids are positioned in the primary sequence, using the spatial proximities of polypeptide chain protons, as observed in the NOESY spectrum. The principal secondary structures (alpha helix, beta sheets, etc.) are then identified by their specific connectivities. The tertiary structure is detected by NOESY connectivities between protons of different amino acids which are far apart in the primary sequence. The distance constraints from the NOESY connectivities also provide the starting point for modeling the tertiary structure. This is then refined using distance geometry and molecular dynamics algorithms. The resolution of the structures obtained with the help of recent algorithmic developments may be comparable to that provided by X-ray diffraction. The COSY measurement can be completed or substituted by other measurements, useful albeit more complex. For example, the HOHAHA experiment, currently in wide use, gives the correlations through multiple covalent bonds. Multiquanta experiments, which select systems of a given number of coupled spins, provide spectral simplification.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1910734 TI - Properties of phospholipase A2 isolated from rat serum. AB - Phospholipase A2 was extensively purified (1300- to 1400-fold) from rat serum using Sephadex G-100 chromatography. It eluted at a position corresponding to a molecular mass of about 15 kDa. This one purification step gave two bands on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The faster component had a molecular mass of 16 kDa and the slower band likely contained an aggregate of the faster component. Activity was associated with protein bands on nondenaturing gels. Enzyme activity was assessed using phosphatidylcholine or phosphatidylethanolamine labelled at sn position 2 with radioactive arachidonate. Phosphatidylethanolamine gave higher specific activities than phosphatidylcholine. The enzyme has an absolute requirement for Ca2+ and a pH optimum at 7.4. This pH optimum was more prominent for phosphatidylethanolamine. Activity was inhibited by oleate or arachidonate when phosphatidylcholine was used as substrate, but added free fatty acid did not significantly affect the hydrolysis of phosphatidylethanolamine. Addition of bovine serum albumin (fatty acid free) to assays increased the rate of release of arachidonate from phosphatidylcholine, but not from phosphatidylethanolamine. Phospholipase A2 is present in serum likely as a consequence of blood coagulation and may release fatty acids from cellular membranes following hemorrhage. PMID- 1910735 TI - Analysis of RNA for transcripts for catalase and SP71 in rat hearts after in vivo hyperthermia. AB - Hyperthermic stress induces synthesis of the major inducible (heat) stress protein (SP71) in all rat tissues. In addition, there is an increase in catalase activity in hearts at 24 and 48 h after the induction of the heat shock response. To more precisely define some of the molecular aspects of the induction of the heat shock response in hearts, we examined mRNA levels for the catalase, SP71 and HSP27. RNA was isolated from control hearts and at various time periods (0-24 h) of recovery after brief hyperthermic treatment and was analyzed by Northern blot analysis using as probes cDNA sequences for rat liver catalase, human HSP70 (inducible), and human HSP27. There was no detectable change in mRNA for catalase after heat shock or during recovery. Hyperthermic stress has no apparent effect on the regulation of transcription of mRNA coding for catalase, indicating that the increase in catalase activity is either translationally or post translationally regulated. The human HSP70 cDNA did not hybridize to control heart RNA, but did hybridize to SP71 transcripts at 0, 1.5, and 3 h post heat shock. The mRNA level for SP71 peaked at 1.5 h, was reduced at 3 h, and became almost undetectable at 6 h post heat shock. Similarly, the human HSP27 cDNA did not hybridize to control heart RNA, but did hybridize to transcripts for HSP27 at 0, 1.5, 3, and up to 15 h post heat shock. Maximal signal for HSP27 was at 3 h post heat shock and was sharply reduced at 6 h post heat shock.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1910736 TI - Gene expression during cold and heat shock in wheat. AB - Translatable messenger RNAs expression was compared in cold- and heat-stressed winter wheat (Triticum aestivum L. 'Fredrick' and 'Norstar') and spring wheat (T. aestivum L. 'Glenlea'). Polyadenylated RNA isolated from the crown and leaf tissues was translated in a wheat germ cell free system and the acidic and basic in vitro products were resolved by two-dimensional SDS-PAGE and autoradiography. The results showed that low temperature stress rapidly induced two groups of mRNAs. The first group was transient in nature and consists of 18 mRNAs that reached their highest levels of induction after 24 h of low temperature exposure and then decreased to undetectable levels. The second group consists of 53 mRNAs that were also induced or increased rapidly, but maintained their levels of expression during the 4 weeks required to induce freezing tolerance. Among those, at least 34 were expressed at higher levels in the freezing tolerant winter wheat compared with the less tolerant spring wheat. This suggests a possible relation between the expression of these mRNAs and the capacity of each genotype to develop freezing tolerance. In the case of heat shock, 50 mRNAs were induced or increased after 3 h at 40 degrees C. Among these, the expression of only six mRNAs was altered in a similar manner in the three genotypes by both treatments. The remaining mRNAs code for typical heat shock proteins which are different from those induced by low temperature. None of these mRNAs has been associated with the development of freezing tolerance. These results suggest that heat and cold stress are controlled by different genetic systems. PMID- 1910738 TI - The myogenic contribution to coronary autoregulation. AB - It seems now, mainly from the results of the experiments carried out in the Department of Human Anatomy and Physiology of the University of Turin, Italy, that there is an active myogenic response in the coronary vessels. In response to changes in the transmural pressure, both increases and decreases, in the coronary vessels transient contractions and relaxations (respectively) of the smooth muscle wall can be demonstrated. Although this suggested mechanism can not be fully integrated into a hypothesis explaining autoregulation of blood flow in the coronary vessels it does seem a strong possibility that it takes part; but further investigation will be necessary to clarify all aspects of this kind of regulation. PMID- 1910737 TI - Qualitative changes in the fluorescence spectra of intact pea leaves after photoinhibition. AB - In high light (1400 W m-2) treated, intact pea leaves, a decrease in the ratio of fluorescence emission at 685 to 730 nm and an increase in fluorescence intensity between 500 and 600 nm were observed. Furthermore, photoacoustically monitored heat emission increased slightly, and O2 evolution decreased significantly. These findings are interpreted as effects of a photoprotective mechanism separating the carotenoid pool from the chlorophylls. This is supported by fluorescence excitation measurements and the results of a study on the reversibility of the process. PMID- 1910739 TI - Proliferation and degeneration of circulating CFU-GM in 15 adult normal subjects. Can any ontogenetic relationship be deduced from these data? AB - We studied, in 15 normal adults, the "in vitro" proliferation and differentiation of circulating CFU-GM, in order to assess their implication in the processes that regulate the dynamic equilibrium of granulopoiesis, analogous to bone marrow CFU GM, and to deduce by their growth behaviour the ontogenetic relationship between CFU-GM subpopulations in the circulating and bone marrow compartments respectively. We found that "in vitro" proliferation of circulating CFU-GM predominates over their degeneration. We believe circulating CFU-GM and bone marrow CFU-GM are not implicated in granulopoiesis regulation in the same manner, and that circulating CFU-GM are more immature than bone marrow CFU-GM when taking proliferation and GM-CSF response into account. One cannot ignore the hypothesis that cells that "in vivo" are quiescent, are recruited "in vitro" with GM-CSF. Finally we would like to draw attention to the parallelism between CFU-GM classification in types 1 and 2 using monoclonal antibodies to track surface antigens, and our classification obtained by using a new mathematical model that takes the "birth" and "dead" of cellular aggregates into account. PMID- 1910740 TI - [Anatomic connections between homotopic transplant of fetal cortical tissue and optic thalamus in adult rats]. AB - The present research was planned to study the possibility to reconstruct a damaged neural circuitry by replacing the injured neurons with homotopic fetal cells. In adult rats the motor cortex was injured with intracortical injection of kainic acid solution. After a delay of 10-14 days, a block of cerebral cortex of fetal rats (E17) was transplanted in the cavity produced by the kainic acid in the motor cortex. After 2-3 months, WGA-HRP solution was injected in the thalamus of the host and both anterogradely labeled fiber terminals and retrogradely labeled somata cells were researched in the transplanted cortex. The results showed that: 1) the host thalamus projects to the transplanted cortex with less density compared to the host cortex surrounding the transplant; 2) the thalamic projection to the transplant is not topographically organized whereas the projection to the host cortex is; 3) the transplant was virtually void of a significant projection to the thalamus of the host. In conclusion, the results offer direct evidence that the reconstruction of an injured thalamocortical circuitry of adult rat is not possible by transplanting homotopic fetal neurons. PMID- 1910741 TI - [Motor organization of the lateral cerebellar nucleus of the rat]. AB - The motor organization of the nucleus lateralis (NL) of the cerebellum of the rat was investigated by studying the motor effects following the electrical microstimulation. The movements evoked by the NL stimulation concerned prevalently the forelimb and the head segments. The movements of the hindlimb segments were evoked in only few cases. The NL is organized as a mosaic of zones without, or at least very little overlap. The various body segments are differently represented in the NL. Some of them are once represented (single representations). In other cases, the same movements were evoked by different NL regions (multiple representations). Finally, in a last lot of cases, various representations concerned the same body regions but from each representation a different type of movement was evoked (specific representations, i.e. displacement of an individual digit and flexion of all digits together). The topographical distribution of the representations in the NL cytological regions (magnicellularis, NLm; dorsolateral hump, DLH; subnucleus lateralis parvocellularis, slp) suggests the idea that each of them may be concerned in a specific motor activity: the NLm would control the position of the body, or of part of it, in the space; the DLH would be concerned in the oral (prevalently) and in the forelimb motor activity; the slp would be concerned in the exploration of the environment as well as in skilled movements of the distalmost forelimb segments. PMID- 1910742 TI - Effect of stimulus mode on middle latency auditory evoked potentials in humans. AB - Middle Latency Auditory Evoked Potentials (MLAEPs) were recorded in 35 healthy subjects; all underwent monaural stimulation and 18 of them additionally underwent binaural stimulation. The aim of the study was to determine the effect of stimulus mode on MLAEP Na, Pa and Nb components and to assess normative data for clinical purposes. MLAEPs were respectively obtained from Cz-ipsilateral ear lobe (monaural mode) and from Cz-A1 and Cz-A2 (binaural mode) by twice averaging 1000 responses to 65 dBHL alternating clicks delivered at a repetition rate of 8.1 Hz. Time base was 100 msec; analogical band-pass filter setting was 5-1000 Hz (off-line digital badpass: 20-100 Hz). The statistical analyses (paired t-test, repeated measures analysis of variance) were not able to demonstrate any differences that derived from differing sides of stimulation (monaural mode) or from differing recording derivations (binaural mode); on the contrary, we demonstrated a slight increase in waveform amplitudes when the binaural mode was employed. In particular, we observed an increase in Na-Pa peak-to-peak amplitude, whereas Pa-Nb amplitude was unmodified. This finding is explicable in terms of a binaural interaction effect. Finally, we propose some guidelines for the correct performance and evaluation of MLAEPs in clinical practice. PMID- 1910743 TI - Oxalate desensitising treatment of dentinal surface. AB - It is well known that a typical painful feeling is caused by impact of different agents and by thermodynamic conditions upon the dentine layer of the tooth. Therefore the action by artificial solutions should be tested to study how the induced modifications might inhibit the pain. The aim of the present study is to evaluate by scanning electron microscopy (SEM) the morphology of dentine surface after different chemical treatments. Oxalate solutions are able to produce a layer of large crystals, while acid solutions remove the smear layer and open the dentinal tubules. PMID- 1910744 TI - Dental composite resin porosity and effect on water absorption. AB - The aims of this study were: 1) to characterize the solubility and water absorption of different composite resins used as dental restorative materials; 2) to analyse their surface morphology using S.E.M. The resins tested were a mixture of glycidyl methacrylate (Bis-GMA) and TEGMA filled with silane-coated particles of inorganic fillers, and Bis-GMA and urethane resin. Cylindrical samples of composite resin were polymerized and stored in distilled water and weighed after different times. SEM analysis demonstrated voids and porous in several samples. The present study shows that dental restorative composite loose a small percentage of their components during storage time and that the type of resin, the nature of fillers and the methods of polymerization greatly influence water uptake and solubility of dental composite resin materials. These findings could explain the loss of anatomic form and the occlusal degradation of dental composites in "in vivo" conditions. PMID- 1910745 TI - Influence of the fluoride ion in the stability of bone hydroxyapatite achieved in patients after the fluo-calcic therapy. AB - It has been proposed that fluoride ion might actively enter into the basic structural framework of the bone, within its main constituent, the hydroxyapatite (HA), by substituting systematically the OH- ion in the crystal chemical formula Ca5[(PO4)3OH]. Accurate compositional studies have become necessary in order to explain an eventual stabilizing effect. Loss in weight (TG) and chemical reaction (DTG) while varying the temperature have been carried out for the first time on specimens under normal conditions and after fluo-calcic treatment, in parallel with accurate chemical compositional determinations by atomic absorption analysis. Our investigation shows that the new structure present after treatment is mechanically stable and proves more resistant to osteolytic processes. PMID- 1910746 TI - [Plankton from the Riva Trigoso Bay(Ligurian Sea): presence of various trace elements]. AB - Between March and June 1989 zooplankton and sea-water samples were taken in three different areas of Riva Trigoso Bay (eastern Ligurian Sea) every two weeks. The analysis of eight trace elements (Cd, Co, Cr, Cu, Fe, Ni, V, Zn) was conducted by means of a graphite furnace atomic absorption spectrophotometer (GFAAS). Biological material values resulted to be limited and quite homogeneous in all metal species thus with no apparent influence from sampling area or time. Observed concentrations (ng/g dry weight) ranged between 12 and 45 for Cd, 52 and 117 for Co, 30 and 71 for Cr, 428 and 1063 for Cu, 730 and 1440 for Fe, 265 and 512 for Ni, 361 and 510 for V, and 1403 and 2499 for Zn. Sea-water values confirmed the results of biological material thus testifying a particularly interesting environmental condition due to low contamination level detected in this part of the coast. PMID- 1910747 TI - The barrier inventory: a study on obesity and multiple sclerosis. AB - The Barrier Inventory was administered to a group of obese patients and group suffering from multiple sclerosis. Both achieved a B score significantly lower than the controls'. These results are in line with those achieved by other patients treated with the Rorschach test; this proves the Barrier Inventory's validity. PMID- 1910748 TI - A national medical waste management policy "still unclear" according to OTA report. PMID- 1910749 TI - Ambient air arsenic levels along the Texas-Mexico border. AB - The Texas-Mexico border region is one of the most rapidly developing areas in the state. Unprecedented economic and demographic growth is placing stress on a system already overburdened with air, water, waste, and public health problems. This paper reports the results of an initial survey of the past and present ambient air levels of arsenic along the Texas side of the border. Ambient air arsenic levels have increased over time, exhibit seasonal variations, and are higher in specific areas when compared to the rest of the state. Five of the 20 areas in Texas having the highest 24-hour levels of arsenic are found along the border. In areas where emissions have been significantly reduced at the source, arsenic levels remained high in the environment for over two years. This provides a potential continuum for human exposure. The results of this study emphasize the need for bi-national development and implementation of air quality control programs along the Texas-Mexico border. PMID- 1910750 TI - The transfer of trichloroethylene (TCE) from a shower to indoor air: experimental measurements and their implications. AB - Experiments were performed to measure the transfer of trichloroethylene (TCE), a volatile organic compound (VOC), from tap water in showers to indoor air. In these experiments, the loss of TCE from tap water in the shower is based on the difference between influent and effluent concentrations. We have developed and previously published a three-compartment model, which we use to simulate the 24-h concentration history of VOCs in the shower, bathroom, and remaining household volumes resulting from the use of contaminated tap water. An important input to this model is the transfer efficiency of the VOC from water to air. The experiments reveal that the transfer efficiency of TCE from shower water to air has an arithmetic mean value of 61 percent and an arithmetic standard deviation of 9 percent. Analysis of the results shows that there is no statistically significant difference between the transfer efficiency measured with hot (37 degrees C) or cold (22 degrees C) shower water and that there is no statistically significant change in transfer efficiency with time during a 20-min shower. The implications for exposure assessment are considered. PMID- 1910751 TI - Laboratory evaluations of the thermal degradation properties of toxic organic materials in sewage sludge. AB - Laboratory thermal decomposition studies were performed to evaluate potential emissions from sewage sludge incinerators. Precisely controlled thermal decomposition experiments were conducted on sludge spiked with mixtures of hazardous organic compounds, on mixtures of pure compounds without sludge, and on unspiked sludge. Experiments were conducted in nitrogen and air atmospheres with gas phase reaction times of 2.0 seconds over the temperature range 300 degrees C 1000 degrees C. It was found that sludge inhibited the decomposition of moderately stable spiked contaminants but accelerated the decomposition of the most stable components. This effect was attributed to radical scavengers produced by the sludge matrix at lower temperatures which then decomposed at higher temperatures. A multiple hearth simulation study suggested that most of the organic material present in the sludge matrix is vaporized within the upper hearths that are held at lower temperatures and may consequently escape from such incinerators undestroyed. A number of stable byproducts resulted from the sludge decomposition that may be of environmental concern. PMID- 1910752 TI - Evaluation of risks from urban air pollutants in the southeast Chicago area. AB - Region V of the U.S. Environmental Protection Agency has conducted a comprehensive study of cancer risks from urban exposure to air pollutants in the Southeast Chicago area. This study estimated emissions of a list of 30 air carcinogens from a broad range of nontraditional, as well as traditional, source types. Using dispersion modeling and applying the appropriate unit risk factors and population data, this study estimated the risks at each receptor location and the total number of cancer cases attributable to air pollution in the area. This analysis estimated that current concentrations would cause 77 cases of cancer over the next 70 years, an average risk of 2.0 X 10(-4). Contributions from different source types and different pollutants were estimated. The total contribution from nontraditional source types was less than 0.3 percent. Although these estimates are highly uncertain, the study does suggest the nature and general magnitude of cancer risks from air pollution in the urban area studied. PMID- 1910753 TI - U.S. interagency team proposes program to quantify effects of Kuwait oil fires. PMID- 1910754 TI - Dr. Chet Perschbacher, recipient of the 1991 Outstanding Service Award. PMID- 1910755 TI - Getting comfortable with claims-made. PMID- 1910756 TI - Electrical fields, nerve growth and nerve regeneration. AB - The presence of voltage gradients within developing and damaged tissues led to the notion that the resultant electrical fields provide instructional cues to cells. Field effects on avian and amphibian neurones in vitro include increased differentiation, turning of neurites towards the cathode, increased rate of growth towards the cathode, resorption of anodefacing neurites, increased branching and increased filopodial activity. Electric fields enhance regeneration of damaged PNS and CNS neurones in animals as diverse as lampreys, frogs, rats and guinea-pigs, but the mechanisms by which fields produce their effects are not understood. Further examination of the interaction of fields with intracellular elements, such as the cytoskeleton and second messenger systems, may offer some insight. PMID- 1910757 TI - Cerebral blood flow in the anaesthetized immature sheep fetus and the response to hypercapnia. AB - Regional cerebral blood flow (CBF) has been measured in eight anaesthetized, exteriorized, fetal sheep between 58 and 62 days gestation; four were controls, four were hypercapnic (PaCO2 = 78 +/- 5 mmHg, mean +/- S.E.M.). Blood flow values were calculated from quantitative autoradiography following the infusion of [14C]iodoantipyrine into a cannulated fetal placental vein, for the cerebellum, medulla, and five layers of the developing neocortex: cortical plate (CP), subplate zone (SP), intermediate zone (IZ), subventricular zone (SV), and the ventricular zone (VZ). The highest control CBF rates were recorded in the cortical plate (49.3 +/- 7.4 ml min-1 (100 g)-1, mean +/- S.E.M., posterior cortex) and in the ventricular zone (40.5 +/- 4.8, posterior cortex), which at this stage of development are the regions of greatest cell density. The lowest CBF rates were recorded in the subplate zone (23.8 +/- 6.8, anterior cortex) and in the intermediate zone (23.4 +/- 7.6, anterior cortex), which are the regions of lowest cell density. Experimentally induced hypercapnia increased CBF in all brain regions and enhanced the regional pattern of flow. The results provide evidence that CBF in the immature fetal sheep brain (at 58-62 days gestation) is heterogeneous under both control and hypercapnic conditions (especially in the neocortex). Blood vessels of the fetal sheep brain at this early stage of development are clearly responsive to CO2. PMID- 1910758 TI - Osmotic-hypertensive opening of the blood-brain barrier in rats does not necessarily provide access for potassium to cerebral interstitial fluid. AB - The blood-brain barrier was breached in urethane anaesthetized rats by infusing hypertonic mannitol or NaCl at high rate under high pressure into one internal carotid artery. Opening of the blood-brain barrier was confirmed by staining of the perfused hemisphere by intravenous Evans Blue dye. Orthodromic-evoked potentials in CA1 region of hippocampus were transiently extinguished, and the extracellular potential in hippocampus and neocortex shifted in the positive direction during hypertonic infusion. After the hypertonic infusion, the permeability of the barrier to K+ was tested by infusing into the internal carotid artery artificial cerebrospinal fluid in which K+ replaced most of the Na+, raising the concentration of K+ in the blood plasma in the superior sagittal sinus to 13-17 mM. Extracellular potential and interstitial potassium concentration ([K+]O) in hippocampus and neocortex, and evoked potentials in hippocampus, remained unchanged during prolonged infusion of high K+, unless and until spreading depression occurred. After a wave of spreading depression, [K+]O returned to baseline in spite of continued high K+ infusion. We conclude that [K+]O in brain tissue is effectively regulated even when colloidal dye can penetrate the blood-brain barrier, but excess K+ may have entered the cerebral interstitial space in scattered patches outside the region sensed by the ion selective microelectrodes, triggering spreading depression. PMID- 1910759 TI - Unidirectional transport of glucose and lactate into brain of fetal sheep and guinea-pig. AB - The first-passage multiple-indicator dilution method was used to measure blood to brain transport of D- and L-glucose, D- and L-lactate and sucrose relative to 22Na, an impermeable reference tracer, in fetal sheep. Fractional extraction for D-glucose was 0.315 +/- 0.051 (S.E.M.) at normal glucose levels and fell to 0.198 +/- 0.041 at 5.2 +/- 0.4 mM-glucose. Fractional extractions for L-glucose, D- and L-lactate and sucrose were not different from zero. No specific blood-brain transport system was detected for L-lactate in fetal sheep in vivo (fractional extraction = -0.024 +/- 0.019). Uptake of L-lactate into isolated microvessels from fetal sheep cerebrum in vitro showed a slightly higher rate (32.2 +/- 8.9 pmol min-1 (mg protein)-1) than that for D-lactate (22.6 +/- 5.6). In fetal guinea-pigs, the carotid arterial injection method with tritiated water as the permeable reference was used to measure the brain uptake index (BUI). BUI was determined for D-glucose (0.304 +/- 0.065) sucrose (0.008 +/- 0.001), L-lactate (0.418 +/- 0.112) and D-lactate (0.071 +/- 0.024). Unidirectional influx calculated from these measurements and estimates of cerebral blood flow showed that transport would be rate-limiting for cerebral glucose utilization at arterial glucose levels below 0.5 mM in fetal sheep and 1.7 mM in fetal guinea pig. In fetal sheep, but not in fetal guinea-pigs, lactate efflux may be limited by brain-blood transport. PMID- 1910760 TI - Central and peripheral doses of cholecystokinin that inhibit feeding in pigs also stimulate vasopressin and cortisol release. AB - The effects on vasopressin and cortisol secretion of centrally and peripherally administered cholecystokinin octapeptide (CCK) were investigated in conscious prepubertal pigs. Injection of 1.3 micrograms CCK into the lateral cerebral ventricle resulted in a sustained increase in plasma vasopressin after a latency of 5 min but no change in cortisol concentrations. Intravenous injection of 0.7 and 1.3 micrograms/kg CCK initiated a rapid surge (within 2 min) in plasma vasopressin and a later increase in cortisol secretion. The time course of the vasopressin response to the central injection of CCK was found to be similar to the period of behavioural inhibition induced when an equivalent dose of the peptide was given by the same route in an earlier feeding experiment. An analogous situation was also observed when CCK was given peripherally and, in this case, the threshold dose at which the behavioural and endocrine responses were induced was found to be the same. PMID- 1910761 TI - Intracellular degradation of newly synthesized casein in perfused rat mammary gland. AB - Degradation of newly synthesized casein in rat mammary gland perfused in situ was measured by a pulse-chase method using [3H]proline. Casein degradation during secretion was observed in the absence of prolactin, but not with prolactin present. Partial inhibition by chloroquine showed that hormone-dependent degradation occurred intracellularly by a lysosomal mechanism. The study indicates that this post-translational mechanism is a physiological regulator of net casein secretion. PMID- 1910762 TI - The influence of temperature on the effects of acetylcholine and adrenaline on the membrane potential and 86Rb efflux in mouse pancreatic B-cells. AB - Pancreatic mouse islets were used to evaluate the influence of temperature on the B-cell response to acetylcholine and adrenaline. At 20 degrees C, the rate of 86Rb efflux from islet cells was lower, the membrane potential of B-cells was slightly less negative, and glucose-induced electrical activity was characterized by longer slow waves than at 37 degrees C. At 20 degrees C, the acceleration of 86Rb efflux produced by 1 microM-ACh was only reduced by 25%, but its reversibility was slower. Acetylcholine rapidly depolarized the B-cell membrane and increased electrical activity regardless of the temperature. However, this increase was characterized by the appearance of short slow waves of high frequency at 37 degrees C and by continuous spiking at 20 degrees C. Adrenaline (1 microM) inhibited 86Rb efflux at 37 and 20 degrees C, but the amplitude of the inhibition was decreased and its time course and reversibility were altered at the lower temperature. Adrenaline repolarized the B-cell membrane and abolished glucose-induced electrical activity for a longer period at 20 degrees C than at 37 degrees C. In conclusion, no marked decrease in signal transduction occurs at 20 degrees C. This suggests that the difficulty of identifying the currents induced by acetylcholine and adrenaline in patch-clamp experiments performed at room temperature is probably due to the small magnitude of these currents. PMID- 1910763 TI - Effects of the prostaglandin analogue misoprostol on cell proliferation in the canine small intestine. AB - While there are several reports of prostaglandins of the E series being associated with increased mucosal mass in the stomach, their effects on the small intestine are less well documented. A microdissection-based technique was used to measure proliferation and crypt size in the duodenum, jejunum and ileum of dogs given the prostaglandin analogue misoprostol. Six test and six control animals were given an oral dose of 300 micrograms kg-1 day-1 of misoprostol for 11 weeks, a dose-duration combination chosen to optimize the development of gastric hyperplasia. Misoprostol increased both the area of the crypts (P less than 0.001) and the number of mitoses per crypt (P = 0.002) throughout the small intestine. The technique also demonstrated a significant gradient in crypt size and in crypt area from the duodenum to the ileum. There was no statistical interaction between misoprostol and the site studied, suggesting that this trophic effect was systemic or systemically mediated. PMID- 1910764 TI - Influence of ileal resection, type of diet and ursodeoxycholic acid on biliary secretion in rats. AB - We studied the effects of the type of dietary fat and of ursodeoxycholic acid, an exogenous bile acid added to the diet, on bile physiology in rats with 50% resection of the distal small intestine. The amount of fat was the same (4%) in all diets assayed, which differed only in the type of fat, (olive oil in diet A, and 1/3 medium-chain triglycerides, 1/3 sunflower oil and 1/3 olive oil in diet B). The removal of 50% of the distal small intestine raised the de novo hepatic synthesis of bile acids with respect to controls, regardless of whether diet A or diet B was given. The addition to diet B of ursodeoxycholic acid decreased bile flow and osmotic activity of bile acid in resected rats and raised bile acid independent bile flow in comparison to resected rats given diet B without ursodeoxycholic acid. PMID- 1910765 TI - The cholinergic regulation of potassium (86Rb+) permeability in sweat glands isolated from patients with cystic fibrosis. AB - Sweat glands isolated from skin obtained from normal subjects and patients with cystic fibrosis (CF) were pre-loaded with 86Rb+ and superfused with a physiological salt solution and the rate of 86Rb+ efflux was measured as an indicator of cellular potassium permeability. Acetylcholine always evoked a permeability increase in the glands from control subjects and this response could be resolved into calcium-dependent and calcium-independent components. Sweat glands from CF patients did not show such consistent responses. In three individuals the glands were abnormally insensitive to acetylcholine but normal responsiveness was seen in a fourth case. It is proposed that CF can induce dysfunction of calcium-dependent control processes in sweat glands. PMID- 1910766 TI - Additional force during stretch of single frog muscle fibres following tetanus. AB - Single fibres from the anterior tibialis muscles of frogs were used in paired difference experiments to investigate the long-term effect (up to 3.8 s) of tetanic stimulation on fibre stiffness during relaxation. The fibres were stretched from sarcomere lengths of 2.5 microns to 3.0 microns at constant velocities for periods ranging from 0.5 to 1.75 s. The first stretch of each pair took place when the fibres had not experienced a tetanus for at least 5 min. The second stretch took place 20-30 s after the first, but it was preceded by a tetanus (100 Hz stimulation applied for 190 ms; temperature, 23 degrees C). The force produced by the first stretch was subtracted from the force produced by the second to produce a paired difference. The fibres were held at the sarcomere length of 3.0 microns except for a brief period of time immediately prior to the stretches (1200 or 1450 ms). During those periods the fibres were shortened to 2.5 microns (250 ms) and then held at 2.5 microns, regardless of whether a tetanus was elicited, for either 950 or 1200 ms. The second stretch of each pair began either at the end of, or 250 ms after, the last stimulating pulse of the tetanus. At every velocity of stretch, the force produced by the fibres during the stretches was greater when the stretches were preceded by a tetanus than when they were not, and the additional force peaked at the conclusion of the stretches. The additional force, which was produced during the stretches following the tetani, declined for the remainder of the data acquisition period (up to 3 s) following the completion of stretches; it extrapolated to zero at 7-8 s after the completion of the stretches. The magnitude of the additional force was a non-linear direct function of the rate of stretch. Thixotropy or an increased stiffness to stretch was observed in all of the fibres following periods of quiescence. PMID- 1910767 TI - 5-Hydroxytryptamine induces electrogenic secretion and simultaneously activates a modulating inhibitory neural circuit in rat small intestine in vitro. AB - 5-Hydroxytryptamine (5-HT) induces electrogenic secretion across rat jejunum and ileum in vitro expressed as an increase in the short-circuit current. Enhancement of this secretory response by previous serosal addition of atropine (1 microM), hexamethonium (0.2 microM) or yohimbine (0.2 microM), especially in the ileum, indicated that 5-HT simultaneously activates an anti-secretory, inhibitory, enteric, neural, cholinergic-adrenergic pathway (ENCAP). A similar inhibitory ENCAP activated by 5-HT has previously been characterized in rat colon in vitro. PMID- 1910768 TI - Effect of short-chain fatty acids on calcium absorption by the rat colon. AB - An in vivo luminal perfusion technique was used to investigate whether short chain fatty acids influence the absorption of Ca by the rat colon. Na and water absorption were also determined. In the distal colon, acetate and butyrate caused a significant increase in Ca absorption, while the absorption of Na and water were not affected. In the proximal colon, butyrate did not influence Ca absorption, but significantly enhanced Na and water absorption. These results are in part consistent with the presence of a Ca-H exchanger in the apical membrane of the distal colon mediating Ca uptake into the epithelial cell. PMID- 1910769 TI - The role of calcitonin gene-related peptide in gastric mucosal protection in the rat. AB - The presence of circulating antibodies to calcitonin gene-related peptide (CGRP) enhanced the damaging effect of ethanol on the rat gastric mucosa. Taken together with previous experimental and morphological data the results suggest that CGRP released from the peripheral terminals of visceral afferent fibres plays a role in mediating gastric mucosal defence mechanisms. PMID- 1910770 TI - Development and application of a nonradioactive phosphorescent autoradiograph marker. AB - A simple and rapid method for permanently marking autoradiographs is described. This procedure is based on the phosphorescence of light-activated zinc sulfide and the subsequent exposure of x-ray films by this light emission. A lacquer based carrier allows the zinc sulfide to remain in suspension and permits permanent marking onto diverse laboratory substrates such as x-ray films, paper, plastic wraps and nitrocellulose- and nylon-based membranes. An analogous wax based carrier allows marking onto paper and dried acrylamide gels, which is useful for processing large numbers of radioactive DNA sequencing gels on a high throughput scale. These inexpensive and nonhazardous markers will be useful in protocols that use x-ray films, regardless of whether radioactive or nonradioactive detection systems are used. PMID- 1910771 TI - Development of a simplified method for subclass isotyping and screening monoclonal antibodies. AB - A simplified dot-blot procedure for screening and subclass isotyping of monoclonal antibodies is described in which only 0.5-50 ng of antigen and 1 microliter of antibody are needed to perform the test. The results on the nitrocellulose membrane can be stored indefinitely for future reference. This method is less expensive, uses smaller quantities of antigen and antibody, and is faster than presently used enzyme-linked immunosorbent assay techniques or other dot-blot methods. Monoclonal antibodies against Mycoplasma gallisepticum were screened and isotyped using this technique. PMID- 1910772 TI - Rapid preparation of lysate for immunoprecipitation using a low protein-binding micro-filter. AB - A simple method to prepare cell lysate for immunoprecipitation is described. The procedure utilizes filtration of cell lysates by using a low protein-binding filter. This filtration method gave an equivalent result to that of the centrifugation method. PMID- 1910773 TI - Parameters affecting susceptibility of PCR contamination to UV inactivation. AB - Contamination of reagents used for PCR is a serious problem. We have recently reported the remarkable effectiveness of UV light in successful decontamination of PCR reagents when the reagents were contaminated with a 6-kb plasmid, followed by amplification of 750-bp segment from the insert. However, further investigation reveals that segment size, sequence and hydration can have a dramatic effect on the efficiency of UV inactivation. Despite some limitations, UV remains a highly effective means of decontamination. PMID- 1910774 TI - Plasmid fragments as accurate markers for northern blots. PMID- 1910776 TI - Several methods of quick freezing in an ultracold freezer. PMID- 1910775 TI - Use of a reversible polyacrylamide gel cross-linker in western blotting for rapid transfer of a wide size range of polypeptides. PMID- 1910777 TI - An efficient method to dialyze small volumes. PMID- 1910778 TI - An electric inoculating turntable. PMID- 1910779 TI - High-sensitivity DNA detection with a laser-excited confocal fluorescence gel scanner. AB - A high-sensitivity, laser-excited confocal fluorescence gel scanner has been developed and applied to the detection of fluorescently labeled DNA. An argon ion laser (1-10 mW at 488 nm) is focused in the gel with a high-numerical aperture microscope objective. The laser-excited fluorescence is gathered by the objective and focused on a confocal spatial filter, followed by a spectral filter and photodetector. The gel is placed on a computer-controlled scan stage, and the scanned image of the gel fluorescence is stored and analyzed in a computer. This scanner has been used to detect DNA separated on sequencing gels, agarose mapping gels and pulsed field gels. Sanger sequencing gels were run on M13mp18 DNA using a fluoresceinated primer. The 400-microns-thick gels, loaded with 30 fmol of DNA fragments in 3-mm lanes, were scanned at 78-microns resolution. The high resolution of our scanner coupled with image processing allows us to read up to approximately 300 bases in four adjacent sequencing lanes. The minimum band size that could be detected and read was approximately 200 microns. This instrument has a limiting detection sensitivity of approximately 10 amol of fluorescein labeled DNA in a 1 x 3-mm band. In applications to agarose mapping gels, we have exploited the fact that DNA can be prestained with ethidium homodimer, followed by electrophoresis and fluorescence detection to achieve picogram sensitivity. We have also developed methods using both ethidium homodimer and thiazole orange staining which permit two-color detection of DNA in one lane.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1910780 TI - A simplified method for the production of recombinant baculovirus. AB - A simplified method for producing recombinant baculovirus for expression of foreign genes is described. The method utilizes insect cells infected with the wild-type virus before transfection with the plasmid transfer vector, instead of the standard procedure utilizing cotransfection with a plasmid and viral DNA. Recombinant virus is preselected by a limiting dilution dot-blot hybridization procedure, rather than by morphologic criteria alone. In addition, we have found that plasmid purification by anion-exchange chromatography is as efficacious for transfection as plasmid purified by cesium chloride density gradient centrifugation. These modifications allows for an efficient, rapid, inexpensive and more objective protocol for the selection of recombinant baculovirus compared to the conventional protocol. PMID- 1910781 TI - Coated capillaries and additives for the separation of proteins by capillary zone electrophoresis and capillary isoelectric focusing. AB - Strategies reported for the separation of proteins in capillary zone electrophoresis and capillary isoelectric focusing are reviewed. The strategies are grouped into two categories: coated capillaries and buffer/sample additives. Success attained with each case and also, more importantly, the limitations of the methodology are discussed. Recent results from our own laboratory in the area of capillary isoelectric focusing in uncoated, fused silica capillaries using additives are summarized. The advantages and disadvantages of coated columns vs. additives are delineated. PMID- 1910782 TI - Separation of carbohydrates and carbohydrate derivatives by HPLC with cation exchange columns at high pH. AB - Cation-exchange columns were found to be stable when used at high pH and high temperature for high-performance liquid chromatographic separations of carbohydrates and carbohydrate derivatives. Pulsed amperometric detection and refractive index detection were found to be suitable detection modes with these cation-exchange columns. Significant differences in carbohydrate separation selectivity were observed between cation-exchange and anion-exchange columns. PMID- 1910784 TI - Realities of automating OPA HPLC amino acid analyses. AB - The levels of free amino acids in culture medium can easily be monitored by reversed-phase HPLC chromatography on a C18 column following pre-column derivatization with o-pthaladehyde. The method does not require the prior removal of proteins. A guard column does that. When this method was automated, problems started to occur after about eight injections. Peak resolution rapidly degraded. Unidentified matter was retained by the column and produced both interfering peaks and high back pressures. Better resolution of the closely eluting amino acids occurred when both the pH of the loading buffer was increased and the gradient time was lengthened. Special washes and a carefully controlled time of equilibration with the loading buffer helped to minimize back pressure and interfering substances. Other often skipped routine maintenance and solvent handling procedures were also necessary for optimal performance. These modifications made routine runs of 40 plus samples possible as well as dramatically increased the lifetime of the column. PMID- 1910783 TI - Recovery of biologically active enzymes after HPLC separation. AB - The mass and activity recovery of eight different enzymes (two monomeric, six oligomeric) with molecular masses between 25,000 and 240,000 daltons were tested after HPLC separation on three different HPLC instruments (two with stainless steel and one with titanium flow paths). Most of the tested proteins are known to be sensitive to heavy metal ions. Eight wide pore, ion-exchange columns, two size exclusion columns and two hydrophobic-interaction columns were used. Both stainless steel and glass column hardware were used in all three separation modes. The elution times were between 8 and 12 minutes. In almost all cases, the activity recovery was between 90% and 100% compared with a control sample incubated in the chromatographic elution buffer for the same time at the same temperature. A severe activity loss (about 30%) was observed with only one ion exchange column and one enzyme. Neither the column hardware nor the material of the HPLC equipment had any negative effect on the activity recovery of the enzymes tested. PMID- 1910785 TI - [Complete single jaw rehabilitation in metal-porcelain (2)]. PMID- 1910786 TI - [New knowledge of the preheating phase. Some technical suggestions]. PMID- 1910787 TI - Site-specific mutations in a minimal voltage-dependent K+ channel alter ion selectivity and open-channel block. AB - MinK is a small membrane protein of 130 amino acids with a single potential membrane-spanning alpha-helical domain. Its expression in Xenopus oocytes induces voltage-dependent, K(+)-selective channels. Using site-directed mutagenesis of a synthetic gene, we have identified residues in the hydrophobic region of minK that influence both ion selectivity and open-channel block. Single amino acid changes increase the channel's relative permeability for NH4+ and Cs+ without affecting its ability to exclude Na+ and Li+. Blockade by two common K+ channel pore blockers, tetraethylammonium and Cs+, was also modified. These results suggest that an ion selectivity region and binding sites for the pore blockers within the conduction pathway have been modified. We conclude that the gene encoding minK is a structural gene for a K+ channel protein. PMID- 1910788 TI - A G beta protein in the Drosophila compound eye is different from that in the brain. AB - A G protein beta subunit gene (Gbe) is expressed only in the eyes of adult D. melanogaster. This gene was identified by probing a Drosophila head cDNA expression library with monoclonal antibodies to a previously characterized Drosophila G protein beta subunit (Gbb). Immunoblot and Northern analyses demonstrate that Gbe protein and mRNA is not present in Drosophila mutants that lack eyes. Immunocytochemical and in situ hybridization analyses further demonstrate that Gbe is expressed in the eyes but not in the brain, whereas Gbb is abundantly expressed in the brain. The Gbe product is approximately 45% identical to previously identified G beta subunits and defines a new G beta class. Its localization suggests a possible role in phototransduction. PMID- 1910789 TI - The alpha subunit of type II Ca2+/calmodulin-dependent protein kinase is highly conserved in Drosophila. AB - A monoclonal antibody against rat brain type II Ca2+/calmodulin-dependent protein kinase (CaM kinase) precipitates three proteins from Drosophila heads with apparent molecular weights similar to those of the subunits of the rat brain kinase. Fly heads also contain a CaM kinase activity that becomes partially independent of Ca2+ after autophosphorylation, as does the rat brain kinase. We have isolated a Drosophila cDNA encoding an amino acid sequence that is 77% identical to the sequence of the rat alpha subunit. All known autophosphorylation sites are conserved, including the site that controls Ca(2+)-independent activity. The gene encoding the cDNA is located between 102E and F on the fourth chromosome. The protein product of this gene is expressed at much higher levels in the fly head than in the body. Thus, both the amino acid sequence and the tissue specificity of the mammalian kinase are highly conserved in Drosophila. PMID- 1910790 TI - Differential spatial and temporal expression of two type III intermediate filament proteins in olfactory receptor neurons. AB - Olfactory receptor neurons (ORNs) do not express the typical neuronal intermediate filament proteins (IFPs), the neurofilament triplet proteins. Immunocytochemical evidence shows that ORNs coexpress vimentin and peripherin but distribute them differently. Specifically, ORNs contain vimentin in dendrites, cell bodies, and axons, but not in terminals in glomeruli; peripherin is present in axons, but excluded from dendrites, cell bodies, and terminal glomeruli. In adult rats, ORN axon fascicles are variably stained with antisera for peripherin; in juvenile rats, staining of fascicles is uniform. Staining with antibody to vimentin is uniform in both adult and juvenile ORN axon fascicles. The unusual pattern of IFP expression and intracellular sorting may have implications for the unique plastic and regenerative capacities of these neurons. PMID- 1910791 TI - Do old practice habits die hard? PMID- 1910792 TI - The human immunodeficiency virus: knowledge and precautions among anesthesiology personnel. AB - STUDY OBJECTIVE: To compare actual infectious disease precautions with current recommendations and to determine the influence of age, clinical experience, human immunodeficiency virus (HIV) knowledge, previous personal HIV exposure, and education on practices. DESIGN: Direct clinical observations of infectious precautions and preeducation and posteducation surveys of clinical practices and general knowledge of the HIV. SETTING: University teaching hospital. PARTICIPANTS: Forty-six anesthesia department members completed a preeducation survey, and 24 completed a posteducation survey. MEASUREMENTS AND MAIN RESULTS: The survey showed that adequate precautions were used during less than 50% of the routine procedures. Significant positive correlations were found between years of clinical practice and precautions used while inserting vascular catheters. Significant positive correlation was found between years of clinical practice and precautions taken while handling soiled laryngoscopes. Knowledge about the HIV and HIV transmission was limited. We noted a negative correlation between knowledge and precautions during vascular cannulation procedures, emergency department resuscitation, and tracheal suction. More precautions were taken with patients who had proven HIV infections and those at high risk of infection. The posteducation survey demonstrated a significant increase only in the use of gloves during routine procedures. Knowledge scores were only slightly improved and did not significantly reflect infection control practices. CONCLUSIONS: Adequate infectious disease precautions were not taken by anesthesia personnel. An HIV educational program resulted in only a small increase in precautionary measures. PMID- 1910793 TI - Indirect assessment of memory for music during anesthesia. AB - STUDY OBJECTIVE: To obtain evidence for intraoperative registration of auditory information in patients undergoing elective surgery. DESIGN: Within-subject design with three levels of frequency of exposure to music. SETTING: A university hospital and a university language laboratory. PATIENTS: Thirty-four patients scheduled for elective surgery and 20 healthy undergraduate psychology students. INTERVENTIONS: Selections of instrumental ethnic music were played to patients for 0, 3, or 12 exposures in one experiment and for 0, 6, or 24 exposures in another study. The undergraduates heard 0, 3, or 12 exposures of the music while awake. MEASUREMENTS AND MAIN RESULTS: Forty-eight hours after hearing the music, all subjects were tested on their preference for the selections they had heard as well as selections they had not heard. For the patients, the mean preference ratings (in millimeters, mm) on a visual analog scale following 0, 3, and 12 exposures were 73.3 mm, 74.0 mm, and 65.1 mm, respectively, a nonsignificant difference. For the patients who were exposed to the music 0, 6, and 24 times, the mean preference ratings were 64.4 mm, 66.1 mm, and 70.6 mm, respectively, a nonsignificant difference. For the waking participants, the mean preference ratings following 0, 3, and 12 exposures were 55 mm, 66.2 mm, and 62.5 mm, respectively, a significant difference (p less than 0.05). CONCLUSIONS: The anesthetized patients did not exhibit indirect memory for music played intraoperatively, at least to the extent required to demonstrate an exposure effect. PMID- 1910794 TI - Effect of alfentanil on hypnotic and antinociceptive components of thiopental sodium anesthesia. AB - STUDY OBJECTIVE: To determine the effects of alfentanil on the hypnotic and antinociceptive components of thiopental sodium anesthesia. DESIGN: Randomized double-blind study. SETTING: Inpatients at a university-affiliated county hospital. PATIENTS: Eighty unpremedicated ASA physical status I or II female patients aged 18 to 60 years, with a weight range of 50 to 90 kg. INTERVENTIONS: Intravenous injection of thiopental sodium in doses ranging from 1.0 mg/kg to 6.0 mg/kg with or without the addition of alfentanil, 0.01 mg/kg. MEASUREMENTS AND MAIN RESULTS: Dose-response curves were determined for the following three endpoints of anesthesia: eye opening in the response to voice command; eye opening in the response to noxious stimulation induced by pressure on the trapezius muscle; and purposeful movement in the response to the same type of noxious stimulation. The addition of alfentanil, 0.01 mg/kg, markedly decreased thiopental ED50 values for all three endpoints: from 2.6 mg/kg to 1.9 mg/kg (p less than 0.02) for eye opening to voice command, from 3.2 mg/kg to 1.9 mg/kg (p less than 0.0005) for eye opening to noxious pressure, and from 4.2 mg/kg to 2.4 mg/kg (p less than 0.0001) for purposeful movement to noxious pressure. The alfentanil-induced increase in thiopental potency for the antinociceptive effect was greater than that for the hypnotic effect (75% vs 36%, p = 0.02). CONCLUSIONS: Alfentanil strengthened both the hypnotic and antinociceptive components of thiopental anesthesia, although to a different degree: the antinociceptive component more so than the hypnotic, possibly because each component of anesthesia has different underlying mechanisms. PMID- 1910795 TI - Does 360 ml of apple juice ingested before elective surgery worsen gastric volume and acidity in patients given acid aspiration prophylaxis? AB - STUDY OBJECTIVE: To evaluate whether 360 ml of oral clear liquids consumed within 4 hours of elective surgery worsens gastric volume and acidity in patients given acid aspiration prophylaxis. DESIGN: Randomized, unblinded study. SETTING: Main operating room at a U.S. military hospital. PATIENTS: Eighty-three adult inpatients scheduled to receive general anesthesia for elective surgery. INTERVENTIONS: Nineteen patients (Group 1) were given 150 mg of oral ranitidine (two doses), 10 mg of metoclopramide, and 360 ml of apple juice 3 hours before the scheduled start of surgery. Thirty-four patients (Group 2) fasted before surgery but received acid aspiration prophylaxis identical to that given to Group 1. Twenty-three additional patients (Group 3) received no oral fluids or acid aspiration prophylaxis before surgery. MEASUREMENTS AND MAIN RESULTS: The residual gastric volume (RGV) and the pH of Group 1 patients were compared with measurements obtained in the two groups of patients who fasted. RGV measurements in Group 1 (14 +/- 3 ml) were similar to those in Group 2 (11 +/- 2 ml) and were significantly less than (p less than 0.05) those in Group 3 (26 +/- 4 ml). Gastric pH was significantly higher (p less than 0.001) in Group 1 (5.16 +/- 0.69) and Group 2 (5.78 +/- 0.43) than in Group 3 (1.97 +/- 0.27). CONCLUSIONS: Three hundred and sixty ml of apple juice consumed within 4 hours of elective surgery by patients given ranitidine and metoclopramide did not worsen gastric volume and acidity. PMID- 1910796 TI - In vitro comparison of central venous catheters for aspiration of venous air embolism: effect of catheter type, catheter tip position, and cardiac inclination. AB - STUDY OBJECTIVE: To test the relative efficiency of balloon-tipped and plain catheters for aspiration of venous air embolism. DESIGN: The following four single-lumen central venous catheters were studied in a silastic model of the right atrium, tricuspid valve, and vena cavae: (1) the 16-gauge single-orifice catheter; (2) the 14-gauge Bunegin-Albin multiorifice catheter; (3) the 7-Fr pulmonary angiography catheter with balloon distal to orifices; (4) the 7-Fr pulmonary angiography catheter with balloon proximal to orifices. A 10% glycerol water solution was circulated at 3.7 to 4.0 L/min. Catheter tips were positioned at 1 cm increments from -3 to +3 cm around the superior vena cava-right atrial junction with cardiac inclinations of 65 degrees and 80 degrees. Air (10 ml) was infused over 30 seconds; aspiration from the test catheter began 5 seconds later at 40 ml/min for 75 seconds. The balloon catheters were evaluated with the balloons inflated and deflated. SETTING: Experimental laboratory of a university affiliated hospital. MEASUREMENTS AND MAIN RESULTS: Amounts of air aspirated were compared by analysis of variance and Tukey's multiple comparison, p less than 0.05, for all combinations. The 16-gauge single-orifice catheter tested best at a 65 degrees cardiac inclination with 86% of the venous air embolism recovered, while the 14-gauge Bunegin-Albin multiorifice catheter tested best at an 80 degrees cardiac inclination with 62% of the venous air embolism recovered. Both catheters functioned most efficiently at or above the superior vena cava-right atrial junction. CONCLUSIONS: This study demonstrated that efficacy of air recovery depends on catheter type, catheter tip position, and cardiac inclination. No benefit was derived from positioning the catheter tip inside the atrium or from using balloon-tipped catheters. PMID- 1910797 TI - High-dose fentanyl reduces intraoperative ventricular fibrillation in neonates with hypoplastic left heart syndrome. AB - STUDY OBJECTIVE: To determine retrospectively the effect of high-dose opiate oxygen (O2) anesthetic technique on intraoperative ventricular fibrillation in high-risk neonates. DESIGN: Retrospective chart review of different anesthetic techniques in a partially contemporaneous patient group (1981 to 1983). SETTING: Cardiac anesthesia service at a university pediatric hospital. PATIENTS: Forty neonates undergoing Norwood Stage I repair of hypoplastic left heart syndrome. INTERVENTIONS: High-dose fentanyl-O2 anesthesia in 30 neonates and low-dose morphine sulfate 50%-nitrous oxide (N2O) in 10 neonates. MEASUREMENTS AND MAIN RESULTS: Clinical condition assessed by preoperative and intraoperative arterial blood gases, requirements for sodium bicarbonate (NaHCO3), need for inotropic and pressor support, and vital signs. Outcome assessments by intraoperative ventricular fibrillation (frequency before and after bypass) and hospital mortality. Clinical condition and hospital mortality were no different. The frequency of intraoperative ventricular fibrillation was significantly different: 3% with high-dose fentanyl and 50% with morphine-N2O (p less than 0.005). CONCLUSIONS: High-dose opiate-O2 anesthesia in these patients markedly decreased intraoperative ventricular fibrillation. Other clinical reports and recent experimental work suggest that this finding is due to high-dose opiates rather than the avoidance of N2O. PMID- 1910798 TI - Phenylephrine in the prevention of hypotension following spinal anesthesia for cesarean delivery. AB - STUDY OBJECTIVE: Phenylephrine and ephedrine were compared in the prevention of maternal hypotension following spinal anesthesia for elective cesarean delivery. DESIGN: Randomized, double-blind trial. SETTING: Obstetric suite at a university affiliated hospital. PATIENTS: Sixty healthy patients electively scheduled for cesarean delivery under spinal anesthesia. INTERVENTIONS: Patients were randomly assigned to receive either ephedrine (n = 29) in 10 mg intravenous (IV) bolus injections or phenylephrine (n = 31) in 80 microgram IV bolus injections to maintain systolic blood pressure (SBP) above 100 mmHg. MEASUREMENTS AND MAIN RESULTS: Maternal venous, umbilical artery, and umbilical vein blood gases were measured, and neonatal Apgar scores and Early Neonatal Neurobehavior Scale scores were assessed. In the ephedrine group, umbilical artery pH was 7.28 +/- 0.01 (mean +/- SEM), umbilical artery partial pressure of carbon dioxide (PCO2) was 56.6 +/- 1.4 mmHg, and umbilical artery base deficit was 2.2 +/- 0.04 meq. In the phenylephrine group, umbilical artery pH was 7.32 +/- 0.01, umbilical artery PCO2 was 52.1 +/- 1.3 torr, and umbilical artery base deficit was 0.38 +/- 0.35 meq. There were significant differences between the groups in mean umbilical artery pH, PCO2, and base deficit, although all values obtained were within normal limits. There were no significant differences between the groups in the remaining acid-base values, neonatal Apgar scores, Early Neonatal Neurobehavior Scale scores, or frequency of maternal nausea and vomiting. CONCLUSIONS: Phenylephrine is as effective as ephedrine in the treatment of maternal hypotension, and when used in small incremental bolus injections, it appears to have no adverse neonatal effects in healthy, nonlaboring parturients. PMID- 1910799 TI - Low-dose droperidol versus standard-dose droperidol for prevention of postoperative vomiting after pediatric strabismus surgery. AB - STUDY OBJECTIVE: To determine whether a low dose of droperidol is as effective as a high dose in preventing vomiting after pediatric strabismus surgery. DESIGN: Randomized, double-blind study. SETTING: Operating room and recovery room at a university medical center. PATIENTS: One hundred children undergoing strabismus procedures. INTERVENTIONS: Patients were divided randomly into three groups and received either droperidol 75 microgram/kg, droperidol 20 microgram/kg, or saline. MEASUREMENTS AND MAIN RESULTS: Vomiting was assessed in all groups, as was time to discharge and ability to perform a satisfactory postoperative eye examination. Children who received droperidol vomited less frequently than those who did not (p = 0.0521). There was no difference in the frequency of vomiting between the two groups that received droperidol. CONCLUSION: Droperidol 20 microgram/kg is as effective as droperidol 75 microgram/kg in preventing vomiting after pediatric strabismus surgery. Because higher doses of droperidol may sedate some patients, the lowest effective dose should be used. In this study, however, there was no statistically significant difference with regard to length of recovery room stay. PMID- 1910800 TI - Intraocular pressure and hemodynamic changes following tracheal intubation in children. AB - STUDY OBJECTIVE: To determine the optimal time in which to make intraocular pressure (IOP) measurements in children following tracheal intubation. DESIGN: Randomized, controlled trial. SETTING: Operating rooms of a tertiary-care children's hospital. PATIENTS: Thirteen healthy children undergoing elective strabismus correction surgery under halothane and nitrous oxide (N2O) endotracheal anesthesia. INTERVENTIONS: Following induction of anesthesia, patients were randomly assigned to receive stable end-tidal halothane concentrations of 0.5% or 1.0% in 66% N2O. MEASUREMENTS AND MAIN RESULTS: Baseline (preintubation) IOP, heart rate (HR), and mean arterial pressure (MAP) were recorded after 10 minutes of steady-state end-tidal concentrations. These measurements were repeated at 1-minute intervals following tracheal intubation, which was facilitated with atracurium. HR and MAP changes were found to be good predictors of IOP changes. IOP returned to baseline (preintubation) values when HR and MAP returned to preintubation levels. However, IOP measurements under anesthesia may not reflect awake values. CONCLUSIONS: We recommend that IOP be measured only after HR and MAP have returned to preintubation levels in children who have undergone tracheal intubation during halothane and N2O anesthesia. PMID- 1910801 TI - Postextubation laryngeal spasm in an unanesthetized patient with Parkinson's disease. AB - We present a patient with Parkinson's disease who experienced laryngeal spasm after tracheal extubation without having been anesthetized. This patient's trachea was intubated because of respiratory arrest. We postulate that her postextubation laryngospasm was related to Parkinson's disease. PMID- 1910802 TI - Acute hemodynamic effects of indigo carmine in the presence of compromised cardiac function. AB - This report describes the acute hemodynamic effects of indigo carmine in a surgical patient with compromised cardiac function. A 68-year-old woman with stable but severe cardiac dysfunction and renal artery stenosis was scheduled for an elective aortorenal bypass procedure. No hemodynamic instability occurred during the operation until the patient was administered intravenous (IV) indigo carmine 5 ml. At that time, the patient experienced an acute increase in afterload, which resulted in acute left ventricular failure documented by a decrease in cardiac output (CO) and an increase in pulmonary artery pressure (PAP). Until further studies defining the mechanism for its hypertensive side effect are performed, indigo carmine should be used with caution in patients with severe cardiac dysfunction. PMID- 1910803 TI - Impact of aging on preoperative evaluation. AB - Approximately 40% of physician office time and 33% of hospital time are devoted to patients 65 years of age or older. Over half of the older population requires some surgical intervention. Because of decreased physiologic reserve and increased number of underlying medical disorders, the older patient is at increased risk for intraoperative and postsurgical complications. Since cardiovascular, pulmonary, and renal complications are frequent in the elderly patient, the preoperative evaluation should emphasize these organ systems. Risk factors should be assessed initially by a focused history and physical examination and by simple tests. Additional diagnostic testing should be reserved for the patient who is not clearly at low or high risk. For optimal preoperative evaluation of the elderly patient, the physician should identify systemic disease, determine if the patient is receiving appropriate therapy, delineate the operative risks, and make recommendations that can potentially reduce the operative risks and postoperative complications. PMID- 1910804 TI - A thoracic leiomyosarcoma producing tracheal obstruction. PMID- 1910805 TI - Introduction: catalyzing matrix stability. PMID- 1910806 TI - HLA molecules: sentinels of the immune response. PMID- 1910807 TI - HLA antigen expression and malignant mesothelioma. AB - The expression of HLA antigens by a tumor may determine its progression and metastatic potential by influencing the immune response to that tumor. The upregulation of HLA antigen expression on some cell types by interferons (IFNs) may contribute to their antitumor activity. Malignant mesothelioma (MM) is a tumor that has a poor prognosis and is unaffected by conventional therapy, although immunotherapy has not been adequately assessed. In this study, we have examined the constitutive and IFN-inducible expression of class I and class II HLA antigens on MM cell lines using indirect immunofluorescence and Northern blotting. All MM cell lines constitutively expressed class I, but not class II, surface antigen, and all three class I loci (HLA-A, HLA-B, and HLA-C) were expressed. The MM cell lines were heterogeneous in their response to the IFNs. Treatment with IFN-alpha marginally increased class I surface expression, but not class II. Class I mRNA was, however, clearly increased in all cell lines after IFN-alpha treatment, suggesting that class I surface antigen was already maximally expressed. IFN-gamma increased class I mRNA expression in all but one cell line and induced DR expression on three of the cell lines. DQ-beta, but not DQ-alpha, mRNA was inducible in the same three cell lines, but DQ surface antigen was never demonstrable.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1910808 TI - Alveolar epithelial cells block lymphocyte proliferation in vitro without inhibiting activation. AB - In the face of constant exposure to inhaled antigens, precise local regulation of immune responses in the pulmonary alveolar space is essential to achieve a delicate balance between host defense and excessive immune responses that are incompatible with the primary physiologic function of the lung. We postulated that the cells of the alveolar epithelium may have an immunoregulatory role in the lung. Therefore, we have examined the effects of primary cultures of rat type II alveolar epithelial cells on lymphocyte proliferation and on the expression of a number of markers of T-cell activation. Monolayers of alveolar epithelial cells suppressed proliferation and DNA synthesis by concanavalin A-stimulated rat splenocytes. Suppression of [3H]thymidine incorporation was independent of the dose of mitogen and was also apparent when lymphocytes were stimulated with phorbol esters and calcium ionophore, suggesting that the effect was independent of cell surface binding of the lectin. Suppression was reversed 48 h after lectin stimulated splenocytes were removed from co-culture with alveolar epithelial cells. Despite inhibition of lymphocyte proliferation, other markers of T-cell activation were induced normally in lymphocytes cultured with alveolar epithelial cells. Culture with alveolar epithelial cells did not inhibit the the production of interleukin-2 by stimulated lymphocytes. Furthermore, by fluorescence activated cell sorter analysis, equal proportions of stimulated lymphocytes in culture alone or with alveolar epithelial cell monolayers were induced to express receptors for interleukin-2 and for transferrin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1910809 TI - Mechanical properties of HL60 cells: role of stimulation and differentiation in retention in capillary-sized pores. AB - Neutrophil sequestration in pulmonary capillaries occurs prior to the development of lung injury, but the mechanisms by which neutrophils are retained are unclear. We hypothesized that decreases in cell deformability, in the absence of an increase in cell surface adhesive properties, would be sufficient to cause cell retention in a filtration apparatus modeling the pulmonary microvasculature. The myelomonocytic cell line (HL60 cell line) was used to test the hypothesis since these cells were unable to increase adherence in response to n formylmethionylleucylphenylalanine (FMLP) in either the undifferentiated state or when differentiated towards granulocytes. With differentiation, HL60 cell volume decreased, and f-actin organization changed from a thick cortical rim with focal areas of f-actin in undifferentiated cells to a thin rim in differentiated cells. Differentiated cells responded to FMLP by reorganizing f-actin and increasing stiffness. Undifferentiated cells did not exhibit changes in f-actin with stimulation, were stiffer than differentiated cells, and did not increase stiffness in response to FMLP. Cytochalasin D (CD), which disrupted the cytoarchitecture as assessed by confocal microscopy but did not affect cell volume or adherence, decreased the stiffness of undifferentiated and FMLP stimulated differentiated cells, thus suggesting the importance of microfilament organization in the stiffness of these cells. Filtration of cells through 8 microns pores showed that undifferentiated cells were markedly retained and did not exhibit any further retention with FMLP. Differentiated cells exposed to FMLP exhibited a concentration-dependent increase in retention in 8-microns pores that was abolished by CD. In addition, CD reduced retention of undifferentiated cells, indicating that microfilament organization is an important factor in determining a cell's rheologic properties. In conclusion, FMLP-stimulated microfilament reorganization, which increased cell stiffness, was sufficient in the absence of adherence factors to cause cell retention in a filtration system. This lends support to the hypothesis that decreases in cell deformability contribute to neutrophil retention in the pulmonary microvasculature. PMID- 1910810 TI - Wound repair of human surface respiratory epithelium. AB - Surface airway epithelium is frequently injured by noxious inhaled agents, epithelial wound repair may be an important process by which the epithelial barrier integrity is maintained. To evaluate the role of surface airway cells in the wound repair process, we developed an in vitro wounding model of human nasal epithelial respiratory cells in primary culture. Circular wounds were made in the epithelial cell culture by detaching, with a glass capillary, approximately 50 cells from the collagen matrix. Video microscopy and electron microscopy observations demonstrated the contribution of two main events during the repair process: the spreading of the cells at the edge of the wounded surface, and the migration of epithelial cell sheets. Complete wound closure occurred within 5 to 8 h. The inhibition of wound repair by cytoskeleton inhibitors or cellular protein synthesis inhibitors suggested that these factors are involved in the wound repair process of surface airway epithelium. PMID- 1910811 TI - Mesothelial cells produce a chemoattractant for lung fibroblasts: role of fibronectin. AB - Pleural fibrosis may complicate several types of non-exudative pleural injury. Although the pathogenesis of such lesions is poorly understood, it is conceivable that mesothelial cells may recruit fibroblasts to sites of pleural damage. In order to test this possibility, conditioned medium from cultured rat mesothelial cells was tested for chemoattractant activity towards RL-87 rat lung fibroblasts. For this purpose, rat pleural or pericardial mesothelial cells were maintained in vitro for 6 to 96 h. Conditioned medium from each source was obtained at defined culture times and tested for chemotactic activity in a 48-well microchemotaxis assembly. A progressive, time-dependent increase in fibroblast chemoattractant activity was detected in both pleural and pericardial mesothelial cell conditioned medium samples. This effect was maximal in 96-h cultures. Checkerboard analysis revealed that the conditioned medium was truly chemotactic for lung fibroblasts. Characterization of the chemoattractant demonstrated that it was a nondialyzable (greater than 16 kD), thermolabile (100 degrees C for 15 min), acid-stable (pH 2.5), trypsin-sensitive, and pepsin-sensitive protein. The chemotaxin was shown to be fibronectin, since activity was abolished, in a dose dependent manner, by treatment with anti-rat fibronectin antiserum as well as by passage through a gelatin agarose affinity column. This product consisted of two bands on sodium dodecyl sulfate polyacrylamide gel electrophoresis of apparent molecular masses 250 and 220 kD. The secretion of a mesothelial cell-derived fibroblast chemoattractant may play a role in the response of the pleura to injury and in the pathogenesis of pleural fibrosis. PMID- 1910812 TI - Differential expression of hsp70 stress proteins in human endothelial cells exposed to heat shock and hydrogen peroxide. AB - The potential role of oxidative stress conditions in the induction of heat shock proteins was studied in human umbilical vein endothelial cells. We compared the effects of temperature (43 to 45 degrees C), exposure to hydrogen peroxide (H2O2) and oxygen metabolites generated by the enzyme system hypoxanthine-xanthine oxidase (O2- plus H2O2), as well as exposure to 95% O2, on the expression of the major 70-kD heat shock proteins (hsp70). Northern blot analysis indicated that: (1) heat shock induced a rapid and marked increase in hsp70 mRNA levels that reached a maximum during recovery from a 30-min exposure to 45 degrees C; (2) treatment with a 5-mM H2O2 bolus or 50 mU/ml xanthine oxidase also increased hsp70 mRNA levels but to a lesser extent than heat shock (about 10 and 25 times less, respectively); (3) no change was detected after a 5-day exposure to 95% O2. Nuclear run on transcription data and kinetics of mRNA decay in the presence of actinomycin D indicated that the observed increase in hsp70 mRNA levels in both heat-shocked and H2O2-treated cells was mainly due to a transcriptional induction. The kinetics of hsp70 synthesis correlated with the accumulation of hsp70 mRNA. Two-dimensional gel electrophoresis and immunologic analysis of these heat shock proteins revealed a series of at least five distinct hsp70 isoforms induced in heat-shocked cells, whereas only a specific subset of these proteins, mainly one acidic isoform, was induced in very low amounts in response to H2O2 treatment. These results clearly indicate that the endothelial cell responses to oxidative stress and heat shock differ in both qualitative and quantitative terms in respect to hsp70 induction. They also suggest that the intensity of this response to oxidative stress conditions may vary depending on the nature of the oxidative challenge. PMID- 1910813 TI - Accessory cells of the lung. II. Ia+ pulmonary dendritic cells display cell surface antigen heterogeneity. AB - In earlier studies, we had determined that class II (Ia) major histocompatibility complex (MHC) antigen expression in the normal rat lung was limited to dendritic cells and type II alveolar cells. In order to characterize the Ia+ pulmonary dendritic cells of the lung parenchyma, Lewis rat lungs were dissected free of their major airways, enzymatically digested, and serially subjected to density centrifugation on bovine serum albumin, overnight adherence, and immunopanning with a murine anti-rat monoclonal antibody (anti-OX-6) that reacts specifically with class II (Ia) MHC antigens. The purified Ia+ pulmonary cells displayed the morphologic and functional features of dendritic accessory cells, including extended cell processes, absence of nonspecific esterase staining, minimal phagocytosis of latex beads, rapid clustering with T lymphocytes, and co stimulation of T-cell mitogen responses. Detailed immunophenotyping by cytofluorimetry and immunohistology showed that the purified dendritic cells were Ia (OX-6)+, CD45R (OX-1)+, CD45Rb (OX-22)-, ICAM-1+, and OX-43-. As many as 50% of the cells bound heat-aggregated IgG, while a smaller percentage expressed the CD43 sialophorin antigens (W3/13) expressed by a variety of blood-derived cells, and/or the OX-41 and RMA macrophage antigens. We conclude that Ia+ dendritic cells of lung are heterogeneous with respect to their expression of surface membrane differentiation antigens and may prove to be functionally distinct with respect to their accessory activities. PMID- 1910814 TI - Tumor necrosis factor-induced protein phosphorylation in human neutrophils. AB - Protein phosphorylation is central to multiple regulatory processes in cells. Tumor necrosis factor (TNF), a cytokine synthesized by macrophages, effects polymorphonuclear leukocyte (neutrophil) chemotaxis, induces superoxide anion generation, and mediates neutrophil adhesion to endothelial cells. Although protein phosphorylation is almost certainly involved in many TNF-mediated neutrophil functions, little is known about TNF's impact on neutrophil protein phosphorylation. Therefore, we studied human recombinant TNF-alpha-induced protein phosphorylation in human neutrophils. Neutrophils were preincubated with 32PO(4)2- and treated with a variety of stimulatory agents. One- and two dimensional polyacrylamide gel electrophoresis was used to analyze phosphorylated proteins. Phosphoaminoacids were identified by two-dimensional thin layer chromatography electrophoresis. The findings were as follows: (1) TNF induces the phosphorylation of two 16-kD proteins (pI = 5.9 and 6.1) by 5- to 6-fold, and a 57-kD protein (pI = 5.8) by 3- to 4-fold compared with untreated neutrophils; (2) these proteins are phosphorylated as early as 15 min after stimulation with TNF, and phosphorylation is induced by concentrations of TNF as low as 1 ng/ml (10 U/ml); (3) TNF induces the phosphorylation of proteins at either serine or threonine residues and not at tyrosine; (4) TNF-stimulated neutrophils show a unique pattern of protein phosphorylation when compared to neutrophils treated with formylmethionylleucylphenylalanine; (5) lipopolysaccharide does not induce protein phosphorylation in neutrophils; (6) a 16-kD protein is phosphorylated in response to TNF in neutrophils but not in mononuclear cells; and (7) protein kinase inhibitors appear to have no effect on TNF-induced protein phosphorylation. Thus, the mechanism of action of TNF on neutrophils may involve protein phosphorylation. PMID- 1910815 TI - Chondroitin sulfate in sputum from patients with cystic fibrosis and chronic bronchitis. AB - In order to ascertain whether or not the presence of glycosaminoglycans in sputa of patients suffering from chronic bronchial disorders was related to tracheobronchial infection, an electrophoretic procedure was set up. The different acidic macromolecular components of sputum, namely nucleic acids, glycosaminoglycans, and bronchial glycopeptides could be identified in proteolyzed sputum using agarose electrophoresis before and after the action of different enzymes: nucleases, chondroitinases, hyaluronidase and heparinase. This procedure was used to analyze 13 sputum samples from patients suffering from cystic fibrosis (CF) and 12 sputum samples from patients suffering from chronic bronchitis. Chondroitin sulfate was identified in 11 infected sputum samples from patients with CF and also in the noninfected sputum from a patient with chronic bronchitis. These data suggest a relationship between the presence of chondroitin sulfate proteoglycans in sputum and severe tracheobronchial infection in CF. PMID- 1910816 TI - Angiotensin receptor-mediated stimulation of diacylglycerol production in pulmonary artery endothelial cells. AB - The stimulatory effects of angiotensin (Ang) I, Ang II, and Ang III on production of diacylglycerol (DAG), a second messenger, were examined in porcine pulmonary artery endothelial cells. Ang I, Ang II, and Ang III provoked rapid increases in [3H]glycerol labeling of DAG. The stimulatory effect on DAG production was maximal after 1 and 5 min. Pretreatment of cells with angiotensin-converting enzyme activity inhibitors prevented the stimulatory effect of Ang I on DAG production, indicating that Ang II but not Ang I is responsible for increased DAG production. The stimulatory effects of Ang II and Ang III on DAG production were concentration dependent and were maximal at a 10-nM concentration of both Ang II and Ang III. Data from further experiments revealed that the Ang II- and Ang III elicited formation of DAG is derived from the coordinated hydrolysis of membrane phosphatidylinositol and phosphatidylcholine by phospholipase C- and phospholipase D-catalyzed pathways. The angiotensin analogue [Sar1 Ile8] Ang II, an Ang II receptor antagonist, blocked the hydrolysis of phosphatidylinositol and phosphatidylcholine and thus the increased production of DAG by Ang II and Ang III. These results indicate that Ang II- and Ang III-induced stimulation of DAG production in pulmonary artery endothelial cells involves multiple pathways of phospholipid hydrolysis and is mediated by angiotensin receptors. PMID- 1910818 TI - Enhancement of disaturated phosphatidylcholine synthesis by epidermal growth factor in cultured fetal lung cells involves a fibroblast-epithelial cell interaction. AB - Epidermal growth factor (EGF) increases the rate of choline incorporation into disaturated phosphatidylcholine in cultured fetal rat type II cells via an indirect mechanism. Whereas-EGF has no effect on the rate of disaturated phosphatidylcholine synthesis when added directly to type II pneumocytes, the growth factor is effective if it is present during preliminary conditioning of the media by lung fibroblasts. This effect is concentration dependent with a maximal effect at 20 ng/ml. When lung fibroblasts are incubated with both glucocorticoids and EGF, there is no significant effect of the growth factor over and above that seen with the steroid alone. This suggests that the two agents might act via a similar mechanism. This is supported by the observation that each inducer leads to the production by lung fibroblasts of a stimulatory factor that has a similar, if not identical, chromatographic elution profile. We conclude that EGF may contribute significantly to the normal onset of lung maturation by elaborating a fibroblast-derived factor that stimulates phosphatidylcholine synthesis in type II pneumocytes. PMID- 1910817 TI - Cadmium ion-induced alterations of phospholipid metabolism in endothelial cells. AB - Cadmium exposure is capable of causing acute and chronic lung injuries, but the specific pathogenetic mechanisms are uncertain. The effects of cadmium ion (Cd2+) on phospholipid metabolism were examined in cultured bovine pulmonary artery endothelial cells (BPAEC), as endothelial cells appear to be particularly vulnerable to the toxic effects of this metallic ion. Exposure of radiolabeled BPAEC to millimolar concentrations of Cd2+ causes liberation of substantial amounts of [3H]arachidonic acid ([3H]AA), but only small amounts of [14C]stearic acid, from each of the major phospholipid subclasses. Analyses of hydrolytic products in BPAEC radiolabeled with [3H]myo-inositol and exposed to Cd2+ indicate that degradation of complex phospholipids is mediated by phospholipase A2. The ability of BPAEC to incorporate fatty acids or lysophosphatides into complex phospholipids is similarly impaired after exposure to Cd2+, suggesting that the liberation of [3H]AA might be due to impairment of reacylation mechanisms and not to increased hydrolytic activity of phospholipase A2. Of the two enzymes involved in reacylation reactions, Cd2+ is found to inhibit the activity of arachidonyl specific acyl coenzyme A synthetase but not the activity of acyltransferase. Cd2+ also causes a profound time- and dose-dependent depletion of adenosine triphosphate levels in BPAEC, and these changes closely correlate with the liberation of [3H]AA. We suggest that impairment of reacylation mechanisms, and the consequent accumulation of arachidonic acid, may be important in the development of the acute inflammatory reaction that is characteristic of Cd(2+) induced lung injury. PMID- 1910819 TI - Developmental changes in tropoelastin mRNA levels in rat lung: evaluation by in situ hybridization. AB - Alveolarization of the immature lung is thought to be influenced by the presence of elastic fibers that could provide structural support for developing septa. Although morphometric studies have established that alveolar septal development occurs from days 4 to 13 in the neonatal rat, the precise time period over which elastin synthesis occurs has proved difficult to determine. We have evaluated the usefulness of in situ hybridization techniques to follow tropoelastin message expression in parenchymal tissue, small vessels, and bronchioles in the developing rat lung from days 4 through 18. This method proved to be sufficiently sensitive to detect differences in rates of tropoelastin message expression from days 4 through 18 (P less than 0.0001). Peak tropoelastin message expression was observed in the small vessels on day 4 and in parenchymal tissue on days 9 through 11. Because the time course of tropoelastin message expression in small vessels differs from that in parenchymal tissue, the use of lung extracts to analyze rates of tropoelastin synthesis in the developing lung may be in error. PMID- 1910820 TI - Cellular changes in the lungs of adrenalectomized rats following left pneumonectomy. AB - The time course and nature of the cellular response to left pneumonectomy, with or without prior adrenalectomy, were evaluated in the right lungs of male Sprague Dawley rats using morphometric techniques. Animals were studied at days 2, 5, and 14 following pneumonectomy, intervals prior to, during the course of, and following significant compensatory changes in right lung mass. The postoperative increase in right lung mass and volume in pneumonectomized animals involved minimal changes in the ratios of most tissue components, when compared to the lungs of sham-operated controls. A transient disproportionate increase in type II cell volume and epithelial thickness was evident on day 14. Postpneumonectomy changes in the type II epithelium were accentuated in the lungs of adrenalectomized-pneumonectomized animals. Adrenalectomy 5 days prior to pneumonectomy resulted in a substantial increase in the volume of all right lung tissue components, associated with thickening of the alveolar wall and with increases in the volume of both cellular and noncellular interstitium. Effects of adrenalectomy on the endothelium also were evident. In both adrenal-intact and adrenalectomized animals, pneumonectomy increased alveolar number by day 14 but had no effect on the volume of individual alveoli. These results confirm a coordinated pattern of compensatory growth following pneumonectomy in the adrenal intact rat. The data further suggest that in adrenalectomized animals compensatory lung growth is more poorly synchronized, with pronounced postoperative elevations in volume of the interstitial and type II epithelial compartments leading to increased thickness of the alveolar wall. Adrenal hormones thus appear to be required for coordination and control of compensatory lung growth and for rapid restoration of normal tissue structure. PMID- 1910821 TI - Mechanisms of phosphatidylcholine acyl remodeling by human fetal lung. AB - The molecular specificity of phosphatidylcholine (PC) synthesis by the de novo pathway in postmortem samples of human fetal lung (15 to 20 wk of gestation) was determined from the incorporation pattern in isolated microsomal preparations of CDP:[14C]choline into individual molecular species of PC. These analyses are based on the assumption that the molecular species composition of the pool of endogenous diacylglycerol used for PC synthesis by isolated microsomes reflects that of the authentic pool of diacylglycerol converted to PC by intact cells. Comparison of this microsomal incorporation pattern of radiolabel into PC with tissue PC composition suggested that even at this early stage of gestation 50% of lung dipalmitoyl PC was derived from synthesis de novo, with the remainder coming from acyl remodeling mechanisms. Analysis of PC synthesis de novo by organ cultures of human fetal lung showed that these acyl remodeling mechanisms were lost in culture. Despite evidence for differentiation of type II alveolar epithelial cells in culture, equilibrium labeling of PC with [14C]choline over 18 h resulted in a progressive decline in fractional incorporation into dipalmitoyl PC with time in culture. By 4 days in culture, this value was no different from the fractional incorporation of CDP:[14C]choline into microsomal PC in vitro over 3 h. The pattern of PC synthesized was not altered when total PC synthesis was stimulated by exposure of cultures to dexamethasone and tri-iodothyronine but was readily manipulated by exposure to exogenous fatty acids. These results demonstrate for the first time the activity of PC acyl remodeling mechanisms in human fetal lung, well before the initiation of surfactant production.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1910822 TI - Platelet-derived growth factor and growth-related genes in rat lung. I. Developmental expression. AB - The autocrine, paracrine, or systemic growth factors responsible for fetal lung cell growth are not completely defined. The progression-type insulin-like growth factors and epidermal growth factor, or transforming growth factor-alpha acting through the epidermal growth factor receptor, appear to act on the developing lung epithelium. The competence factors that facilitate the actions of progression factors during lung growth are unknown. Fetal rat lung cells in vitro synthesize a platelet-derived growth factor (PDGF)-like polypeptide, which we have hypothesized may play a paracrine role in normal lung development. Slot blot and Northern blot analyses of fetal rat lung mRNA have been used to determine if there is a relationship between expression of message for PDGF-A or PDGF-B chains, or their cognate receptors, and periods of maximal growth during late fetal rat lung development. Whole lung mRNA was extracted on 18, 19, 20, 21, and 22 days of gestation (term = 22 days). The peak of DNA synthesis, as assessed by expression of message for DNA polymerase alpha, histone 3, and the proto oncogenes c-fos and c-myc, which are stimulated by binding of growth factors including PDGF, occurred during the canalicular stage of lung development on days 19 and 20 of gestation. Expression of message for PDGF-A and PDGF-B chains was low during the pseudoglandular stage on day 18, peaked during the canalicular stage on days 19 and 20, then fell again during the saccular stage at days 21 and 22 of gestation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1910824 TI - Systemic macrophage stimulation in rats with silicosis: enhanced release of tumor necrosis factor-alpha from alveolar and peritoneal macrophages. AB - In silicosis, alveolar macrophages (AM) are thought to induce chronic inflammation and fibrosis by release of cytokines. Rats were exposed to aerosols of alpha-quartz and examined 4 to 9 mo later for persistence of silica particles and release of tumor necrosis factor-alpha (TNF-alpha) from macrophages. Silica particles were detected in AM, lung parenchyma, and thoracic lymphoid organs, whereas extrathoracic lymphoid tissues and organs were free of the mineral. When AM were tested functionally, no spontaneous release of TNF-alpha was observed. However, upon in vitro stimulation of AM from silicotic rats with a low concentration of lipopolysaccharide (10 ng/ml), abundant TNF-alpha production was found that was higher and occurred more rapidly than with AM from sham-exposed animals. Peritoneal macrophages, which did not have contact with silica particles, displayed a similarly enhanced TNF-alpha release in response to low doses of lipopolysaccharide. These data demonstrate a state of systemic preactivation ("priming") of macrophages that supports the notion that silicosis is associated with a general immunostimulation. PMID- 1910823 TI - Induction of unilateral pulmonary fibrosis in the rat by cadmium chloride. AB - Intralobar instillation of cadmium chloride (CdCl2) into the left lungs of rats initiated a sequence of events that culminated in massive unilateral intraluminal fibrosis. Early events (days 1 and 2) after CdCl2 administration included infiltration of the treated lung with polymorphonuclear leukocytes, an increase in the number of alveolar macrophages, activation of the macrophages as assessed by the induction of cathepsin L mRNA, and the induction in liver of mRNA for the acute-phase response protein, alpha 1-acid glycoprotein. By days 5 to 7 in the treated lungs, mRNA for procollagen alpha 1(I) increased 20- to 60-fold, and mRNA for procollagen alpha 1(III) increased 4- to 14-fold. These increases were correlated with the almost complete filling of the alveolar spaces with fibroblasts and collagen. The contralateral lung exhibited no significant change in histology but showed a similar induction of collagen gene expression. These increases were tissue-specific, as the livers of these animals showed no change from the control levels of collagen gene expression. Procollagen messages in the treated and contralateral lungs were equally competent for translation into pro alpha 1(I) and pro-alpha 2(I) polypeptides. Both the treated and contralateral lungs increased hydroxyproline content about 1.5- to 2-fold over 14 days. The contralateral lung, but not the treated lung, showed a 2-fold increase in lung volume. As a result, the collagen density (mg collagen/ml lung volume) doubled in the treated lung but remained constant in the contralateral lung. These data indicate that CdCl2 caused a rapid induction of pulmonary fibrosis in the treated lungs of rats and stimulated histologically normal growth of the contralateral lung. PMID- 1910825 TI - Magnetic resonance imaging of ankle injuries. AB - Stress placed on the ankle from sport activity predisposes it to a variety of injuries. MRI, with its multiplanar capability and excellent soft tissue contrast, is uniquely suited for examining the complex anatomy of the ankle. It is the procedure of choice for imaging suspected tendon and cartilage damage. It is also highly sensitive in detecting radiographically occult bone injuries. This review first addresses technical factors important in generating high-resolution images that are crucial for accurate diagnosis in this area. Pathogenesis and MRI appearance of commonly encountered sport-related soft tissue and bone injuries around the ankle are presented and discussed. PMID- 1910826 TI - Tendon injuries of the lower extremity: magnetic resonance assessment. AB - MR is rapidly establishing itself as a premiere imaging modality for the assessment of musculoskeletal trauma. Its utility in the evaluation of the menisci and ligaments of the knee is well known, but there is far less known about the use of MR for evaluation of the tendons. MR, by virtue of its unmatched soft tissue resolution capability, can determine not only the contour of an affected tendon, but the tendon sheath and internal signal alterations that accompany tendonitis, partial and complete ruptures. Injuries to the Achilles tendon are well known to the athlete and the imager alike; however, abnormalities of the posterior tibial tendon, peroneal tendon, and flexor hallucis longus also result in significant clinical symptoms, as well as imaging abnormalities. PMID- 1910827 TI - Magnetic resonance imaging of shoulder impingement. AB - MRI is an accurate technique for diagnostic evaluation of a broad spectrum of shoulder pathology. In particular, rotator cuff injuries are a frequent cause of pain and disability. The mechanism of injury to the supraspinatus tendon usually begins with microscopic tears of fibers of the triple helix collagen molecule. This leads to increased motion of the bound water within the collagen molecule that lengthens the effective T2 of the tendon, allowing short TE imaging sequences to detect signal in abnormal tendons. Clinically significant disease probably does not occur without frank collagen rupture, and the associated collection of free water within the severely diseased tendon presents as high signal on long TE images. Thus, the clinical significance of tendon disease is best evaluated on long TR, long TE image acquisitions. Any process that accelerates microscopic tear formation or delays repair can increase a patient's risk of supraspinatus tendon tears. Impingement is the most important process accelerating microscopic tear formation. MRI's multiplanar, tomographic imaging ability markedly improves the ability to sensitively and specifically detect bony impingement. Hopefully, this will allow earlier arthroscopic decompression and improved patient prognosis with impingement. PMID- 1910828 TI - Exertional muscle injuries: magnetic resonance imaging evaluation. AB - Exertion-related muscle pain is frequent in athletes and patients alike; however, its severity and significance may be difficult to assess clinically. MRI can be used to evaluate myalgia, strains, delayed-onset muscle soreness, chronic muscle overuse syndromes, muscle contracture, and sequellae of muscle injuries such as myositis ossificans and compartment syndrome. MRI documents the distribution of affected muscles, the presence of focal hematoma, fascial herniation, and subsequent healing, fibrosis, or fatty infiltration. MRI is useful in evaluating acute and delayed exertional muscle injuries. PMID- 1910829 TI - Patellofemoral joint abnormalities in athletes: evaluation by kinematic magnetic resonance imaging. AB - The patellofemoral joint is one of the most common sources of painful symptoms encountered by athletes and is one of the most frequently injured joints. Patellar incongruency is the primary pathologic condition that affects the patellofemoral joint and has been reported to be associated with patellar subluxation, patellar dislocation, chondromalacia, and arthrosis. The diagnosis of patellofemoral incongruency by physical examination alone is extremely difficult because the clinical signs may stimulate other types of internal derangements of the knee, and there is a high incidence of combined abnormalities. In consideration of these issues, a kinematic MRI technique was developed to identify and characterize abnormal anatomic and functional aspects of the patellofemoral joint. Because the patellofemoral joint is often injured in athletes and patellofemoral incongruency is a common site of their pain, this article will discuss the use of kinematic MRI to assess the anatomy and function of the patellofemoral joint, with an emphasis toward special problems that may be found in relation to sports-related activities. PMID- 1910830 TI - Transesophageal echocardiographic evaluation of left atrial mass lesions. AB - Transesophageal echocardiography with color flow Doppler studies was performed on 12 consecutive patients who had left atrial mass identified by transthoracic echocardiography. In two patients with atrial myxoma, transesophageal study identified the tumor by its attachment to the atrial septum. In all instances, the tumors were larger and more mobile by transesophageal study and influenced the decision to operate early on an asymptomatic patient. In six instances the masses in the atria were deemed to be thrombi because of associated spontaneous echo contrast, location in the left atrial appendage, mitral valvular disease or prosthesis, atrial fibrillation, congestive heart failure, and enlarged left atrial chamber. In two patients the left atrial masses on transesophageal imaging were large vegetations attached to the mitral valve with ruptured chordae tendineae. In two patients, because of superior quality images obtained by transesophageal imaging, the atrial mass lesions were deemed to be a prominent muscle band between the left atrial appendage and left upper pulmonary vein. In conclusion, transesophageal echocardiography is superior to transthoracic imaging in elucidating the cause and significance of atrial mass lesions and helps in guiding appropriate therapy. PMID- 1910831 TI - Transesophageal echocardiographic evaluation of right atrial mass lesions. AB - Transesophageal echocardiography with color flow Doppler studies was performed on 10 consecutive patients who had right atrial masses identified by transthoracic echocardiography. In one patient with right atrial myxoma, transesophageal study identified the tumor by its attachment to the atrial septum and ruled out the transthoracic finding of possible additional tumor mass in the right ventricle. In two instances the mass in the atria were deemed to be thrombi because of lack of attachment to the atrial septum, atrial fibrillation, and enlarged right atrial chambers. In all patients, the thrombi appeared larger by transesophageal study and was associated in one instance with atrial septal defect. The atrial septal defect was not identified by the transthoracic study and probably accounted for stroke of the patient through paradoxical emboli. In six patients, because of superior quality images rendered by transesophageal imaging, the right atrial mass lesions were deemed to be anatomic variants, which included prominent eustachian valves, remnants of Chiari network, and thickened atrial septum. We concluded that transesophageal echocardiography is superior to transthoracic imaging in elucidating the cause and significance of right atrial mass lesions and that it helps in guiding appropriate therapy. PMID- 1910832 TI - Doppler color flow mapping of the proximal isovelocity surface area: a new method for measuring volume flow rate across a narrowed orifice. AB - This manuscript describes a new method, validated in in vitro models, for quantitating volume flow rate across an orifice with Doppler color flow mapping. Flow through a narrowed orifice is characterized by the convergence of radial streamlines proximal to the orifice. In this color Doppler method, one or more isovelocity surface areas (PISA), delineated by blue and red aliasing velocity interfaces, can be identified proximal to the narrowed orifice. Volume flow rate (in milliliters per second) can then be calculated as PISA (in square centimeters) multiplied by the isovelocity of the PISA (in centimeters per second). Doppler color flow mapping was performed in in vitro models of constant and pulsatile flow through an orifice in a wall. The first proximal isovelocity surface area, with an isovelocity corresponding to the aliasing velocity, that is, one half the Nyquist sampling limit, could be identified as a blue and red color interface proximal to the orifice. Over a range of circular orifice diameters from 3 mm to 16 mm and flow rates from 0.5 to 18.7 L/min, the proximal isovelocity surface area could be imaged in two planes. This PISA was best described by a hemielliptic mathematical model with two different radii measured from long-axis and short-axis views. In the constant flow model, volume flow rate calculated from the Doppler PISA correlated well with actual volume flow rate measured simultaneously with a cylinder and stopwatch (r = 0.98, p less than 0.001, standard error of the estimate [SEE] = 0.36 L/min). In the pulsatile flow model, with jet velocities ranging from 2.6 to 7.7 m/sec and flow volume ranging from 1.0 to 10.3 L/min, calculated volume flow rate also demonstrated an excellent correlation with actual volume flow rate (r = 0.99, p less than 0.001, SEE = 0.53 L/min). Findings from these in vitro models suggest that quantification of the proximal isovelocity surface area by Doppler color flow mapping appears to be a promising technique for estimating volume flow rate across a narrowed orifice. This new color Doppler flow method may have advantages over previous Doppler methods in estimating volume flow rate in various clinical situations, for example, valvular regurgitation and shunt lesions. PMID- 1910833 TI - Left ventricular diastolic dysfunction in end-stage dilated cardiomyopathy: simultaneous Doppler echocardiography and hemodynamic evaluation. AB - Left ventricular diastolic dysfunction is an integral component of end-stage dilated cardiomyopathy. To better characterize this disorder we studied 15 patients undergoing catheterization during cardiac transplant screening evaluation. Pulsed-wave Doppler echocardiographic recordings of mitral inflow were obtained with simultaneous high-fidelity left ventricular and phase corrected pulmonary capillary wedge pressures. Doppler-derived isovolumic relaxation times were within normal limits, despite a prolonged coefficient of relaxation (tau), and correlated with pulmonary capillary wedge--left ventricular crossover pressure. Peak velocity of early diastolic filling was similar to that reported in normal subjects and did not correlate with crossover pressure or tau. Early diastolic acceleration and deceleration times were shortened compared with reported normal values. Acceleration time correlated with mean negative dP/dt from mitral valve opening to left ventricular minimum pressure and with crossover pressure, and deceleration time correlated with mean dP/dt from left ventricular minimum pressure to the peak of the rapid filling wave. Late diastolic filling at atrial contraction was absent in 12 patients, all of whom had a significant early diastolic rapid filling wave and an elevated end-diastolic pressure. Despite an increase in pulmonary capillary wedge pressure during atrial contraction, the failing ventricles were unable to generate detectable forward transmitral flow. Poor cardiac pump function was shown by low left ventricular stroke volume, which correlated with the diastolic flow velocity integral. Thus, in end-stage cardiomyopathy, the transmitral flow velocity pattern is characterized by normal peak early filling velocity, low normal isovolumic relaxation time, shortened acceleration and deceleration times of early diastolic flow, decreased early flow velocity integral, and absent or decreased filling during atrial contraction. This pattern reflects interaction between elevated transmitral driving pressure and the compromised relaxation and compliance of a left ventricle functioning on an elevated pressure-volume curve. PMID- 1910834 TI - Observations on Doppler mid-diastolic mitral flow reversal. AB - Mitral regurgitation is detected occasionally in diastole during severe aortic regurgitation, hypertrophic cardiomyopathy and atrioventricular block. We have noticed mitral mid-diastolic flow reversal in both patients and many normal subjects. To evaluate this flow phenomenon, pulsed Doppler mitral flow velocity and M-mode echocardiographic recordings were obtained in 38 normal subjects (age range, 16 to 61 years). Fifteen of 38 subjects (40%) had mid-diastolic flow reversal, defined as reversed flow occurring in mid-diastole with a duration greater than 50 msec. Mid-diastolic flow reversal was more common in subjects with longer RR intervals (1031 versus 893 msec), more rapid M-mode echocardiographic EF (early diastolic deceleration) slopes of mitral valve anterior leaflet motion (141 versus 93 mm/sec), and more rapid deceleration of early diastolic mitral flow velocities (612 versus 426 cm/sec2). Mid-diastolic flow reversal by Doppler color flow mapping was recorded in the left atrium in all subjects, even in subjects without mid-diastolic flow reversal shown by pulsed Doppler echocardiography. However, subjects with mid-diastolic flow reversal detected by pulsed Doppler echocardiography demonstrated greater extension of flow into left atrium (10.4 versus 4.1 mm) and longer duration (112 versus 69 msec) of color flow reversal. These data suggest that mid-diastolic flow reversal represents a physiologic intravalvular flow that is possibly the result of reflected flow from the vigorous early diastolic mitral semiclosure. PMID- 1910835 TI - The velocity distribution in the aortic anulus in normal subjects: a quantitative analysis of two-dimensional Doppler flow maps. AB - The velocity distribution in the aortic anulus is commonly assumed to be uniform. A skewed velocity profile may have consequences for the accuracy of volume flow estimates by the Doppler echocardiographic technique. To assess this issue, the velocity distribution in the aortic anulus in 12 normal subjects was studied by computer analysis of digital velocity data from two-dimensional Doppler ultrasound flow maps. The velocity profiles in the aortic anulus were found to be flat but slightly skewed, with the highest velocities toward the septum. There was little interindividual variation. Our findings imply that the centerline velocity is the best estimate for the spatial mean velocity at the aortic anulus in normal subjects. The importance of this finding in patients is unknown. In normal subjects, the results suggest that stroke volume might be overestimated by approximately 15% by Doppler echocardiography if the cross-sectional velocity profile is not accounted for. PMID- 1910836 TI - Doppler assessment of pulmonary venous flow in healthy subjects and in patients with heart disease. AB - Pulmonary venous flow as assessed by Doppler echocardiography is a current topic of investigation. Pulmonary venous flow has been used recently as part of a comprehensive assessment of left ventricular diastolic filling dynamics in restrictive myocardial diseases and constrictive pericarditis. Abnormalities of flow have been described in dilated cardiomyopathy, congenital heart disease, and arrhythmias. With the advent of transesophageal echocardiography, pulmonary venous flow can be readily obtained in all patients by pulsed-wave Doppler echocardiography. Recently, it has been used to assess the severity of mitral regurgitation and to estimate mean left atrial pressure. This article emphasizes the utility, physiology, and technique of measuring pulmonary venous flow with Doppler echocardiography in health and in disease. PMID- 1910837 TI - Echocardiographic diagnosis of secondary coarctation complicating the repair of a traumatic pseudoaneurysm of the aorta. AB - An 18-year-old patient underwent repair of traumatic aortic pseudoaneurysm. Postoperatively, the physical examination showed hypertension with 30 mm Hg gradient between the upper and lower extremities. Doppler echocardiographic evaluation demonstrated a new (secondary) aortic coarctation at the site of the repair. Transesophageal echocardiography revealed the detailed anatomy and the cross-sectional area of the coarctation. PMID- 1910838 TI - Spontaneous drainage of paravalvular abscess diagnosed by transesophageal echocardiography. AB - Paravalvular abscesses, which occur in up to 30% of cases of native valve endocarditis, are being detected with increasing frequency with the use of transesophageal echocardiography. Abscesses of the mitral aortic intervalvular fibrosa have been described but only in association with native or prosthetic aortic valve endocarditis. We describe a patient with native mitral valve endocarditis complicated by an abscess in the fibrosa. A 51-year-old diabetic man presented with Staphylococcus aureus mitral valve endocarditis. A transesophageal echocardiographic study done 8 days after admission revealed two large masses at the base of the anterior mitral leaflet with extension into the fibrosa consistent with a paravalvular abscess that was not detected by precordial echocardiography. A repeat transesophageal echocardiographic study done 20 days after admission showed spontaneous drainage of the abscess and a subsequent fistula between the left atrium and left ventricle. This case highlights the important role that transesophageal echocardiography has in suspected and known cases of endocarditis. Its major advantage of delineating posterior cardiac structures allowed accurate diagnosis and serial evaluation of this previously unreported complication of endocarditis. PMID- 1910839 TI - Aortic valvular fibroma as a source of systemic emboli in POEMS syndrome. AB - In a young woman with POEMS syndrome and two systemic embolic events, transesophageal echocardiography revealed a small mobile aortic valve mass. At surgery, an aortic valvular papillary fibroma, with areas of attached thrombus, was removed. This case underlines the importance of transesophageal echocardiography in identifying cardiac sources of emboli. PMID- 1910840 TI - Echocardiographic detection of left circumflex coronary artery to left superior vena cava fistula by use of Doppler color flow mapping. AB - We report the two-dimensional and Doppler color flow mapping echocardiographic findings in a neonate with left circumflex coronary arteriovenous fistula to a left superior vena cava. Doppler color flow mapping, in concert with detailed imaging, was essential to identify this rare fistula and to prepare for therapeutic intervention at initial cardiac catheterization. PMID- 1910842 TI - Left atrial tamponade: diagnosis by transesophageal echocardiography. AB - A 60-year-old white man became hypotensive and dyspneic 3 days after right pneumonectomy for bronchogenic carcinoma. Transthoracic echocardiography was nondiagnostic because of technical difficulty. Transesophageal echocardiography demonstrated a loculated posterior pericardial effusion with isolated diastolic left atrial collapse. The hemodynamic disturbance resolved after drainage of the effusion. Transesophageal echocardiography plays a valuable role in the diagnosis of postoperative cardiac tamponade. PMID- 1910841 TI - Pulsus paradoxus: a definition revisited. AB - Pulsus paradoxus is associated with many clinical conditions and is defined as a greater than 10 mm Hg end-inspiratory decrease in systolic blood pressure. Kussmaul's original definition of pulsus paradoxus is presented, along with an explanation of his choice of the term "pulsus paradoxus." A case of pulsus paradoxus is graphically described using simultaneous two-dimensional targeted M mode, Doppler echocardiographic, and high-fidelity pressure recordings. PMID- 1910844 TI - Entire left anterior fetal papillary muscle and chordae tendineae sonographically demonstrated functioning in systole at 18 weeks' gestation. PMID- 1910843 TI - Transesophageal echocardiographic diagnosis of cardiac rupture. AB - Cardiac rupture is a difficult pre-mortem diagnosis to make and is equally difficult to manage. Transesophageal echocardiography may be useful in expediting the diagnosis and in the management of cardiac rupture related to myocardial infarction. PMID- 1910845 TI - Effect of high-volume cardioplegia on small-amplitude electrical activity during cardioplegia arrest. AB - The effects of high-volume cardioplegia on the presence of small-amplitude electrical activity during cardioplegia arrest were investigated in 19 mongrel dogs. The animals were randomly assigned to receive either high-volume crystalloid cardioplegia (HV-plege) or crystalloid cardioplegia guided by continuous electrical monitoring (V-plege). Cardiac index, left ventricular stroke work index dp/dt, and myocardial oxygen consumption were measured before bypass and following 90 min ischemia and 45 min reperfusion. Biopsies were taken for measurement of adenosine triphosphate (ATP) and examination of myocardial ultrastructure. Nine animals received HV-plege, while the remaining 10 animals received cardioplegia guided by voltage criteria. Small-amplitude electrical potentials were recorded within 10-15 min after the infusion of cardioplegia in all animals receiving cardioplegia guided by voltage criteria. Electrical activity, however, was immediately abolished by reinfusion of cardioplegia. HV plege reduced the incidence of small-amplitude electrical activity during cardioplegia arrest but did not prevent electrical activity. Left ventricular function and myocardial ultrastructure were better preserved when cardioplegia was guided by electrical monitoring. ATP decreased similarly in both groups following cardioplegic arrest, but myocardial oxygen consumption was significantly higher following the arrest in the V-plege group. CONCLUSIONS: HV plege does not prevent small-amplitude electrical activity and may have adverse effects on myocardial metabolic and functional recovery. PMID- 1910846 TI - Cold blood cardioplegia and warm cardioplegic reperfusion in heart transplantation. AB - The major cause of early death after heart transplantation is graft failure. In 99 consecutive heart transplantations two protocols of myocardial protection were employed. In group 1 (n = 38) initial cold crystalloid cardioplegia combined with cold saline storage and peroperative surface cooling was used. In group 2 (n = 61) cold crystalloid cardioplegia was injected initially and cold blood cardioplegia (Buckberg) was infused every 30 min as soon as the graft arrived in the operating room. No surface cooling was used. Warm blood cardioplegic reperfusion was administered before removal of the aortic clamp. There were 8 early (within 30 days) deaths in group 1 and 6 in group 2 patients. In group 1 there were 5 cardiac deaths against 3 in group 2. Mean ischemic time was 153 +/- 37 min in group 1 and 158 +/- 51 min (p greater than 0.05) in group 2. The post transplantation need for catecholamines was ten times higher in group 1 patients than in group 2. The first endomyocardial biopsy (after 1 week) showed cytologic lesions compatible with ischemia in 40% of group 1 and only 9% in group 2 patients. We conclude from this initial experience that intermittent cold blood cardioplegia and warm blood cardioplegic reperfusion are useful in heart transplantation in restoring the damage suffered by the graft during brain death and graft storage. PMID- 1910847 TI - Pulmonary metastasectomy in patients with osteosarcoma. AB - Between 1980 and 1990, 70 patients with high malignant osteosarcoma of the extremities were treated according to the European Osteosarcoma Intergroup trials. Of the 31 patients with metachronous metastases (group I), 17 underwent pulmonary metastasectomy. Six of the 17 survived 8 months to 4 years after metastasectomy without evidence of recurrent metastatic disease. The type of orthopedic surgical treatment had no influence on the disease free interval (DFI), nor on the overall survival. The DFI was significantly longer (P less than 0.003) in patients with resectable pulmonary metastases. Overall survival was not influenced by the length of the DFI. Six of 11 patients with synchronous metastases (group II) underwent pulmonary metastasectomy, 1 survived longer than 7 months. Nevertheless, overall survival is not significantly different between group I and group II (P = 0.2): 28 patients without pulmonary metastases (group III) had a 95% survival at 5 years. In patients with metachronous metastases, metastasectomy independently had a positive effect on survival (P less than 0.001), but did not cure the patients. Strict patient selection and additional therapy to prevent micrometastases is needed to improve survival. PMID- 1910848 TI - Assisted circulation for myocardial recovery after repair of congenital heart disease. AB - Between January 1987 and May 1990, six children underwent ventricular assisted circulation for recovery of myocardial function after cardiac surgery. Their ages ranged from 9 months to 12 years. Three patients had tetralogy of Fallot and one had atrioventricular discordance with ventriculoarterial concordance, ventricular septal defect, and under-over ventricles. Double outlet left ventricle and a large ventricular septal defect with pulmonary hypertension was present in the remaining two. The duration of circulatory support averaged 126 +/- 57 h. An extracorporeal membrane oxygenator (ECMO) was used in four patients, biventricular assistance with centrifugal pumps in one, and left ventricular assistance followed by ECMO in the last patient. Circulatory support was begun in the operating room in two patients who could not be weaned from cardiopulmonary bypass. Both these patients are long-term survivors. Assisted circulation was implanted in four patients in the intensive care unit because of low cardiac output refractory to any pharmacological treatment. Only one of these patients could be weaned from circulatory support but he died 20 days later because of multiorgan failure due to persistent poor myocardial function. The causes of death in the remaining three patients were intracranial hemorrhage, untreatable bleeding, and failure of myocardial recovery, respectively. We believe that early postoperative use of circulatory support can be a major determinant for recovery of myocardial function in patients who have severe low cardiac output following repair of congenital cardiac lesions. Our initial experience with the use of biventricular assistance in small children is encouraging. Nevertheless, further observations are clearly necessary to establish the role of postoperative circulatory support in children with congenital cardiac lesions. PMID- 1910849 TI - Evaluation of a new finger-type intraoperative epicardial echocardiographic probe for infants and small children. AB - A new finger-type epicardial echocardiographic probe was evaluated in 26 children with complex cardiac anomalies during open heart surgery. The probe is a small 3.75 MHz phased array transducer for 2-dimensional echo and color Doppler imaging. The tip is slightly angled to facilitate the apical approach through a median sternotomy. The patients included 4 neonates and 8 infants, and the major cardiac lesions were complete atrioventricular (AV) canal, transposition of the great arteries, double outlet right ventricle, and others. The intraoperative study was possible in most of the patients facilitating various approaches for the assessment of left-sided AV valve function, left ventricular outflow obstruction, residual shunt and intraatrial anatomy. Four patients received subsequent operative procedures after the assessment. This transducer appears to be useful in the intraoperative study during surgery for complex cardiac anomalies in neonates and small infants. PMID- 1910850 TI - Surgical treatment of large pericardial effusions. Etiology and long-term survival. AB - From 1977 to 1988 60 patients were treated for large pericardial effusion. The operation consisted of a small left anterior thoracotomy with formation of a pericardial window. In 28 patients (47%) the etiology was a malignant disease. Eight patients (29%) had malignant cells in the pericardial fluid and 23 patients (82%) had metastases to the pericardium. Seven patients (12%) had purulent pericarditis; in 4 cases Staphylococcus was found. Of the remaining 25 patients, the etiology remained unknown in 13. The 5-year survival rate was 60% among patients with nonmalignant effusions. In patients with malignant effusions only 20% were alive after 2 years. There were no deaths related to the operation. We conclude that large pericardial effusions of unknown etiology can be safely treated with a small left anterior thoracotomy. This access gives optimal possibilities for rapid diagnosis and treatment. PMID- 1910851 TI - Bronchoalveolar lavage in the prediction of post-thoracotomy chest infection. AB - A prospective study was carried out on 75 patients undergoing pulmonary surgery to determine the relationship between perioperative lung flora and postoperative infections. Seventy-five patients having pleurectomy or pneumonectomy received cefuroxime prophylaxis; 1.5 g i.v. at induction followed by 6 further doses of 0.75 g i.v. over 48 h. Bronchoalveolar lavage samples were taken perioperatively via bronchoscopy in pleurectomy patients and from excised lung in patients undergoing lung resection. Patients were monitored for development of chest infection during the first 10 days after operation. Bacterial pathogens were cultured from 12 out of 54 lavage samples. The most common pathogen was Haemophilus influenzae and all the organisms were sensitive to cefuroxime. Eight patients (10.7%) developed postoperative chest infection. The likelihood of developing postoperative chest infection was 42% (5 out of 12 patients) in those patients whose lavage culture was positive for bacterial pathogens compared to 4.8% (2 out of 42 patients) for those whose culture was negative (chi 2 test, p less than 0.001). These results suggest that the culturing of bacterial pathogens from lavage samples from resected lung is a significant predictor of postoperative chest infection in patients undergoing pulmonary resection. PMID- 1910852 TI - Recurrent atrial arrhythmias following treatment for postoperative atrial fibrillation after coronary bypass operations. AB - Ambulatory Holter monitoring was performed in 58 patients during the early convalescence after myocardial revascularization in order to determine the incidence of recurrent atrial arrhythmias following treatment for postoperative atrial fibrillation. Fifteen patients who had undergone coronary bypass and had not developed spontaneous atrial fibrillation following operation served as the controls (group 1). The remaining patients developed spontaneous symptomatic atrial fibrillation after coronary bypass that required digitalization for rate control. Sixteen patients (group 2) continued taking digoxin for 8 weeks following operation, 13 patients (group 3) discontinued digoxin treatment 5 weeks following operation, and 14 patients (group 4) discontinued digoxin treatment 3 weeks following operation. Twenty-four-hour Holter monitoring indicated that asymptomatic atrial fibrillation was common in the treatment groups after digitalization just before discharge from hospital. Atrial fibrillation, however, rarely recurred following discharge from hospital and was never symptomatic. Our data indicate that patients who develop spontaneous postoperative atrial fibrillation should be treated with digoxin for 3 weeks following operation and then drug therapy may be discontinued indefinitely. PMID- 1910853 TI - The role of surgery in the management of solitary coronary artery aneurysm. AB - A 55-year-old lady presenting with angina was diagnosed on angiography as having a solitary aneurysm of a lateral circumflex artery. She underwent clipping of the aneurysm and a long saphenous vein bypass graft to the distal vessel. The role of surgery in the management of coronary aneurysms is discussed. PMID- 1910854 TI - False passage in the interventricular septum. PMID- 1910855 TI - Surgical treatment of aortico-left ventricular tunnel. PMID- 1910856 TI - Immunoglobulin heavy chain allotypes in a sample of Sicilian patients with celiac disease. AB - The authors have studied the immunoglobulin heavy chain allotypes in 14 Sicilian patients with celiac disease (CD) and in 75 healthy controls. No association has been found between CD and Gm or Km phenotypes. When the role of Gm phenotypes in immune response against gliadin was analyzed, fb-positive CD patients on gluten free diet for 1 year showed an increased antigliadin IgG response. Comparing the values of fb-positive subjects with those of negative ones, a significant difference was observed. These data, demonstrating that the presence or absence of a phenotype is able to define the breadth of immune response against alpha gliadin antigen, are indicative of the role played by Ig allotypes in CD. PMID- 1910857 TI - Immunoglobulin allotypes in systemic lupus erythematosus--results of a central European multicenter study. SLE Study Group. AB - Immunoglobulin heavy chains (G1m, G2m, G3m, A2m) and kappa light chain (Km) allotype and phenotype frequencies were examined in 323 central European Caucasian patients with systemic lupus erythematosus (SLE). No significant differences were found between the different allotype or phenotype frequencies of the SLE patients and a control group of healthy individuals. Our results indicate that Gm, A2m and Km allotypes do not represent susceptibility factors for SLE in Caucasians. PMID- 1910858 TI - Monoclonal anti-A and anti-A,B antibodies from a mouse immunized with A secretor saliva. AB - Using spleen cells from a mouse immunized with blood group A secretor saliva, we obtained 3 monoclonal anti-A antibodies (3H9, 5C6, 4D8) and 1 monoclonal anti-A,B antibody (2D10). In agglutination tests against red cells of A subgroups, 3H9 gave similar results to human anti-A serum, and 2D10 reacted with both A and B cells. 5C6 agglutinated especially A1 cells, while 4D8 showed stronger agglutination of A2 cells than the other antibodies. Using these antibodies, it is possible to distinguish the subgroups of A. The 4 antibodies had no reactivity with the red cells of 6 animal species and nonhuman primates except for group A anthropoid apes. All 4 antibodies were negative with Cad-positive, sheep and papain-treated O red cells that are agglutinated by the A-cell-reactive lectins. The activity of 3H9 was inhibited by A secretor saliva and that of 2D10 by both A and B secretor salivas. 4D8 showed a weak reaction with A secretor saliva. Antibody 5C6 was inhibited rather strongly even by A nonsecretor saliva. Thus, 5C6 is useful for application to test specimens in legal medicine, such as examination of blood or salivary stains for A antigens. PMID- 1910859 TI - Investigation of blood group A substance in the circulation of a patient with ovarian cyst. AB - Blood group substance was investigated in serum, cyst fluid and ascites of a patient with mucinous cystadenoma of the ovary. The patient's blood group was A, Le(a-b+), secretor. The serum contained so abnormally large amounts of A substance that it was difficult to determine the ABO blood of the patient's red cells. Using neutralization of anti-A, the ovarian cyst fluid was estimated to contain about 4,000 and 1,500 times as much substance as the serum before removal of the cyst and ascites, respectively. The A substance in serum reverted to a normal level 13 days after removal of the cyst. Gel infiltration analysis of the serum, ascites and ovarian cyst fluid showed the presence of similar A substance with a molecular weight ranging from one to several millions. These data indicate that A substance from the ovarian cyst entered the blood stream, and disappeared from it after the cyst was removed (half-life: 1 day). PMID- 1910860 TI - DNA analysis in a MHC heterozygous patient with complete C4 deficiency- homozygosity for C4 gene deletion and C4 pseudogene. AB - Virtually all cases of inherited C4 deficiency appear to be caused by homozygosity for rare MHC haplotypes carrying combined defects of genes coding for the C4A and C4B isotypes. The present analysis concerned a C4-deficient patient with two different MHC haplotypes, [HLA-A2, B40, SC00, DR6] and [HLA-A30, B18, F1C00, DR3]. Digestion of genomic DNA from the patient with Taq I and probing with a 5' cDNA C4 probe and a CYP21-specific probe gave only a 7.0-kb and a 3.7-kb band, respectively. The analysis of restriction fragment length polymorphism in family members showed that both C4-deficient haplotypes contained a C4 pseudogene at the C4 locus I and a CYP21 gene together with a deletion of the C4B gene and the adjacent CYP21P gene. None of the C4 pseudogenes contained C4A- or C4B-specific nucleotide sequences as judged from hybridization studies of polymerase chain reaction products. The findings illustrate the high degree of polymorphism in C4 genes and that both gene deletions and presence of a C4 pseudogene are common as reasons for C4 null alleles. The rare C4 double null alleles appear to have arisen in different MHC haplotypes independently. PMID- 1910861 TI - Recombinant interferon-gamma differently affects DQA and DRA gene expression in two human melanoma clones: transcriptional and posttranscriptional regulation. AB - In a previous study, two human melanoma HLA class-II-negative clones have been shown to respond differently to recombinant interferon gamma (rINF-gamma). In fact, in clone 9229/18, rINF-gamma treatment led to a coordinate expression of both DR and DQ genes, whereas in clone 9229/5, a high increase in steady-state mRNA levels and cell surface antigen expression could be observed for DR but not for DQ genes. The molecular mechanism underlying such a different behavior was investigated and DQA gene regulation was studied both at the transcriptional and posttranscriptional level. Nuclear run-on experiments were performed on 9229/5 and 9229/18 clones. Treatment with rINF-gamma at 1,000 U/ml for 24 h led to a coordinate transcriptional activation of DRA and DQA genes in 9229/18 clone, whereas in clone 9229/5 it strongly augmented the rate of transcription of DRA but not DQA genes. For all class II genes studied, both melanoma clones showed a basal rate of transcription that never led to a mature cytoplasmatic mRNA. To study whether posttranscriptional mechanisms could affect DQA mRNA stability, a comparison was performed between mRNA turnover in 9229/18 cells treated with actinomycin D and actinomycin D plus cyclohexamide following rINF-gamma treatment. In the absence of protein synthesis, the t1/2 of specific DQA mRNA was largely reduced, showing that a short-lived protein is required to stabilize human DQA mRNA in melanoma cells. Our results indicate that DQA gene is subjected to a tight regulation, acting both at the transcriptional and posttranscriptional levels and that DQA and DRA genes can be differentially regulated at the transcriptional level by rINF-gamma in a melanoma clone such as 9229/5. PMID- 1910862 TI - A rare GC mutant in horses disclosed by isoelectric focusing and subsequent immunoprinting. AB - An apparent incompatibility in the GC/DBP system in a mare and her colt was found after classification by polyacrylamide gel electrophoresis. Because of this observation an analysis of the equine GC/DBP system by isoelectric focusing and subsequent immunoprinting was initiated. Further GC subtypes, however, were not encountered: the three phenotypes GC F, FS and S were also delineated by this method. The GC types in the case of disputed descent were dissolved: GC S was found in the mare and GC FS in her colt as well as in another of her male offspring. It is proposed that a rare GC mutant is responsible for this observation, namely a GC S* component which is readily classified by isoelectric focusing and immunoprinting and difficult to disclose by polyacrylamide gel electrophoresis. PMID- 1910863 TI - Low levels of hydrogen peroxide enhance platelet aggregation by cyclooxygenase activation. AB - Platelet aggregation can be triggered by addition of exogenous arachidonate owing to its conversion to endoperoxides and thromboxane A2. The dose-response curve of arachidonate-induced platelet aggregation exhibited a very steep slope. Simultaneous addition of H2O2 (1-200 microM) significantly shifted this curve to the left. H2O2 alone did not induce aggregation up to a concentration of 1 mM; however, a reversible increase of cytoplasmic Ca2+ and a small increase of the thromboxane levels could be observed. In the presence of exogenous arachidonate H2O2 led to an increased formation of arachidonate metabolites. Our data demonstrate that at threshold levels of 20:4 H2O2 is able to promote conversion of 20:4 to proaggregatory prostaglandin endoperoxides, and subsequently platelet activation is facilitated. Thus we support the evidence for a role of H2O2 in the activation of cyclooxygenase possibly by providing an adequate peroxide tone. PMID- 1910864 TI - Arachidonate 15-lipoxygenase; characteristics and potential biological significance. AB - Arachidonate 15-lipoxygenase (an n-6 lipoxygenase) has been purified to homogeneity, cloned and expressed and appears to be a highly regulated enzyme showing pronounced tissue specificity. The enzyme is expressed prominently in the reticulocyte where it appears to be under posttranscriptional control and may play a key physiological role in reticulocyte maturation by initiating mitochondrial breakdown. 15-Lipoxygenase is also expressed in significant quantities in airway epithelial cells and eosinophils although no clear role for this enzyme in these cell types has been defined. The enzyme catalyzes the conversion of free arachidonic acid to 15-HPETE, free linoleic acid to 13-HPOD and can also oxygenate polyenoic acids esterified in phospholipids. A number of potential physiological and pathological roles for products of this enzyme have been postulated. These include a physiological role in prolactin secretion from pituitary cells and in the initiation of the acrosome reaction in spermatozoa. An important pathological role in the oxidation of LDL by macrophages has also been proposed, indicating that the enzyme could be a pharmacological target for the treatment of atherosclerosis. PMID- 1910865 TI - Preparation, metabolic stability and biological properties of omega trifluorinated analog of 12-hydroxyeicosatetraenoic acid. AB - 12-Hydroxyeicosatetraenoic acid (HETE) is associated with a variety of inflammatory conditions. For studies on pathophysiological function of 12-HETE, metabolically more stable analogs of 12-HETE would be useful. We biologically synthesized 20,20,20-trifluoro-12-HETE (20-F3-12-HETE) by incubating enantioselectively synthesized 20,20,20-trifluoro-arachidonic acid with human platelets. The product was identified by UV absorption spectrophotometry and gas chromatography-mass spectrometry. When 1 microgram 20-F3-12-HETE was incubated with 5 X 10(6) human neutrophils for 45 min, only 5% of the analog was metabolized while 66% of 12-HETE was metabolized in the same incubation condition. With 2 X 10(7) neutrophils, 37% of the analog was metabolized at the same incubation condition while 87% of 12-HETE was metabolized. Thus, by blocking omega-oxidation of 12-HETE with fluorine atoms, the stability of 12-HETE was greatly increased. This result indicates that the omega-oxidation is a major pathway for 12-HETE metabolism. The analog demonstrated as much chemotactic activity on human neutrophils as 12-HETE, and binding affinity of the analog for 12-HETE receptor in human epidermal cell was equal to that of 12-HETE. An analog of 12-HETE, which has extended metabolic stability without alteration of neutrophil chemotactic activity and binding affinity, would be a useful tool for studies on pathophysiological role of 12-HETE in inflammatory conditions. PMID- 1910866 TI - Lipoxin A4 elevates cytosolic calcium in human neutrophils. AB - Lipoxin A4 (LXA4), a lipoxygenase-derived metabolite of arachidonic acid, stimulated a dose-dependent elevation in cytosolic free Ca2+ concentration, [Ca2+]i, in fura-2-loaded human neutrophils, with an EC50 of 0.4-0.5 microM. The time for [Ca2+]i to peak was also dose-dependent. In the presence of extracellular Ca2+ (CaDT-PA added), the rise in [Ca2+]i was due to a combination of Ca2+ release from internal stores and influx of extracellular Ca2+. In the absence of extracellular Ca2+, the rise in [Ca2+]i was due to release from internal stores, which then became depleted. No response to LXA4 was seen in the absence of divalent cation chelators (EGTA or DTPA); this is presumably because LXA4 forms an inactive complex with heavy metal cations. In the presence of extracellular Ca2+, LXA4 had no effect on the subsequent response of neutrophils to the chemotactic peptide fmetleu-phe (fmlp). In the absence of extracellular Ca2+, LXA4 dose-dependently reduced the subsequent response of neutrophils to fmlp; this is presumably because LXA4 discharges the store, and so reduces the amount of Ca2+ available for subsequent release by fmlp. PMID- 1910867 TI - Hepoxilin A3 increases vascular permeability in the rat skin. AB - We have recently shown that hepoxilins are formed by and act on human neutrophils leading to an increase in intracellular levels of calcium and activation of the release of arachidonic acid and diacylglycerol [6, 9]. Since neutrophil activation and accumulation is involved in the inflammatory process resulting in vascular permeability in the rat skin, we investigated the effects of hepoxilins on this process. Hepoxilins administered s.c. resulted in a concentration- and time-dependent leakage of dye to the extravascular compartment of skin from rats to which Evans Blue had been administered. These results were compared to experiments in which prostaglandin E2 was used. The threshold dose of hepoxilin that elicited an effect reached a level of significance over control within 5 min of administration at the 10 ng dose (139% +/- 7%, n = 6). Similar findings were obtained with prostaglandin E2, the level of significance was reached also at 5 min at the 10 ng dose (177% +/- 7% of control, n = 6). The maximum effect observed for both hepoxilin and prostaglandin E2 was 60 min although this did not differ significantly from 30 min except for the highest dose of PGE2 (100 ng). However, the extent of the effect observed for prostaglandin E2 was greater than that for hepoxilin after longer periods, i.e. at 60 min, the prostaglandin E2 effect being 238% +/- 10% of control, and hepoxilin A3 being 167% +/- 10% of control. These results demonstrate that hepoxilins may participate in inflammatory processes. PMID- 1910868 TI - Beneficial effects of the prostacyclin analogue taprostene on cardiovascular, pulmonary and renal disturbances in endotoxin-shocked rabbits. AB - The prostacyclin analogue taprostene protects against lethal endotoxemia in rats. In the present study, the effects of taprostene on endotoxin-induced cardiovascular, pulmonary and renal alterations have been investigated. In anesthetized rabbits, infusion of 0.5 mg/kg Escherichia coli lipopolysaccharide i.v. over 30 min produced systemic hypotension, pulmonary hypertension, and decreases in cardiac output, peripheral oxygen delivery and renal glomerular filtration rate. In endotoxemic rabbits treated with taprostene (0.2 micrograms.kg-1.min-1 i.v. over 180 min), the blood pressure tended to be lower than in untreated endotoxemic controls. Taprostene reduced the total peripheral resistance and abolished the endotoxin-induced increases in pulmonary artery pressure and resistance. Taprostene prevented the decreases in cardiac output and peripheral oxygen supply. At the end of the experiment the glomerular filtration rate was higher in taprostene-treated than in untreated endotoxemic rabbits and did not differ significantly from that in non-endotoxemic controls. The results show that taprostene prevents the pulmonary hypertension, preserves cardiac output and peripheral oxygen delivery, and substantially maintains the glomerular filtration rate in endotoxin-shocked rabbits. PMID- 1910869 TI - The epidemiology of toxic stews. AB - 'Toxic stews' is a term which refers to the innumerable manmade chemicals to which we are exposed today. Neither their composition nor their toxicity in humans and the environment is sufficiently understood. Little interest has been aroused thus far by synergisms between these substances. The sources of toxic stews are many and diverse: chemical products and associated impurities; industrial and household waste water; emissions from combustion, incineration and other industrial processes; exhaust fumes from traffic and power plants; etc. These negative aspects of modern life contribute to the development of chronic diseases such as cancer, allergies, and diseases of the respiratory tract and central nervous system. There are severe obstacles to, and deficiencies, in official monitoring of pollutants, including problems of data access, chemical analysis, and toxicological and epidemiological research. It is urgent that the role of the physician as guardian of human health be expanded to include a stronger emphasis on environmental protection as an important component of preventive medicine. PMID- 1910870 TI - Pollution, carcinogenesis and cancer prevention. AB - Epidemiological and other data indicate that most cancer is due to environmental factors in the broader sense of the term and, therefore, presumably preventable to a great extent. Consequently, the identification of carcinogens in the environment is of fundamental importance in cancer prevention. Oncogene research has given new insight into the cellular signal pathways, as well as genetic alterations leading to neoplastic growth. This information provides a foundation for improvement of the current testing strategy for carcinogenic chemicals released into the environment. The testing protocols must take into consideration the carcinogenic agents that act through both genotoxic and non-genotoxic mechanisms. Also, it should be pointed out that human exposure often involves complex mixtures of chemicals, and the possibility of interactions between initiating and promoting carcinogens. Current test procedures rarely deal with such chemical interactions. Analyses of environmental factors responsible for the induction of cancer in humans indicate that naturally-occurring, rather than man made, chemicals constitute a prevalent cancer risk. It must, however, be stressed that this conclusion applies to Western industrialized countries. In eastern European and developing countries, environmental pollutants, synthetic pesticides and other man-made chemicals very likely pose a larger cancer risk for the general population. PMID- 1910871 TI - Spreading the message. Building a general consensus on the environment. AB - In communicating an environmental message to society at large, it is useful to distinguish between decision-makers and the general public. The influence of decision-makers on public debates is as significant as their ability to implement decisions; in democratic societies, the two functions are inseparable. Proceeding from an environmental consensus, physicians can provide a source of impartial medical/ecological wisdom, and serve as mediators of public debates. For those purposes, a network of physicians and/or scientists can be useful; three examples are provided. Communicating to the general public can only be achieved economically through the mass news media, which operate under conditions very different from those of physicians and scientists. There is considerable room for improvement in environmental journalism, and physicians can make a useful contribution to any such process. It is an important issue, since the mass media constitute the 'ecology textbook' of the general public. PMID- 1910872 TI - From the Big Bang to sustainable societies. AB - A series of events in the history of cosmos has created the prerequisites for life on Earth. With respect to matter, the earth is a closed system. However, it receives light from the sun and emits infrared radiation into space. The difference in thermodynamic potential between these two flows has provided the physical conditions for self-organization. The transformation of lifeless matter into modern life forms, with their high degree of order and complexity, has occurred in the context of the earth's natural cycles, including the water cycle and the biochemical cycles between plants and animals. Primary production units, the cells of green plants, can use the thermodynamic potential of the energy balance in a very direct way, i.e. in photosynthesis. Plant cells are unique in their ability to synthesize more structure than is broken down elsewhere in the biosphere. The perpetuation of this process requires the recycling of wastes. However, modern industrial societies are obsessed with the supply side, ignoring the principle of matter's conservation and neglecting to plan for the entire material flow. As a result there has been an accumulation of both visible and invisible garbage (pollution), which disturbs the biosphere and reduces stocks of natural resources. Furthermore, due to complexity and delay mechanisms, we usually cannot predict time parameters for the resulting socio-economic consequences or the development of disease. To continue along this path of folly is not compatible with the maintenance of wealth, nor with the health of humans or the biosphere. Rather than address the millions of environmental problems one at a time, we need to approach them at the systemic level. It is essential to convert to human life-styles and forms of societal organization that are based on cyclic processes compatible with the earth's natural cycles. The challenge to the developed countries is not only to decrease their own emissions of pollutants but to develop the cyclic technology and life styles needed by the entire human community. PMID- 1910873 TI - Organization of DNA sequences highly repeated in tandem in rice genomes. AB - Digestion of the total genomic DNA from rice Oryza sativa L. cv. C5924 with EcoRI generated an intense band of a DNA fragment of about 0.36 kb long. The DNA fragment cloned into pUC19 was used to hybridize with the total rice genomic DNA partially digested with EcoRI. A ladder of bands of DNA fragments with multiplied length of 0.36 kb was observed, demonstrating that this sequence occurs in tandem in the genome. The copy number of the sequence estimated by dot blot hybridization analysis was 2000-3000 copies per haploid genome from callus or seedling of C5924. This sequence was present in other O. sativa cultivars, such as Sasanishiki in 700-900 copies, Koshihikari in 3400-4300, and Nipponbare in 4600-6000 copies. Another rice species, O. glaberrima, also had this sequence in 540-680 copies, but four lines of foxtail millet had none. The DNA fragments containing the repeated sequences in Nipponbare were then cloned into lambda EMBL3, and sequences of nine units consecutively repeated and an AT-rich sequence connected with them in a phage clone could be determined. Each repeating unit showed sequence divergency mostly by substitution of bases in a range from 3% to 7%, when compared with a 355-bp consensus sequence. Analyses of the substituted bases indicate that these are due to spontaneous mutations which occurred at random, after reiteration of a unit sequence by unequal crossing over events. Gene conversion within the repeated sequences might have further diversified their sequences. PMID- 1910874 TI - Hybrid dysgenesis in Drosophila melanogaster: a new type of gonadal dysgenic sterility expressed at the pre-pupal stage. AB - Two sublines, B-202 and B-207, which were derived from crosses between Or-R (M) females and Cy/Pm (P) males were found to cause a new type of gonadal dysgenic sterility, designated as the GD-3. GD-3 sterility showed a typical reciprocal cross effect under the P-M system. It was caused at the frequency close to 100% in dysgenic offsprings reared above 25 degrees C, of which gonads were morphologically clearly different from those of usual GD sterility, whereas there was no indication of GD-3 sterility at temperatures below 24 degrees C. Temperature sensitive period of GD-3 sterility was estimated to the prepupal stage by shift-down experiment. In the B-202 subline, the 2nd chromosomes marked with Pm alone carried GD-3 elements. Those of the B-207 subline, however, were estimated to locate both on the 2nd and 3rd chromosomes, acting synergistically with each other. PMID- 1910875 TI - Left ventricular thrombi in acute myocardial infarction. Clinical reality or morphologic entity? PMID- 1910876 TI - [Intraventricular thrombi in acute myocardial infarct. The Iberian Multicenter Study. Presentation of the study protocol and various preliminary results]. AB - OBJECTIVE: To evaluate the incidence of left intraventricular thrombosis and systemic embolism after acute myocardial infarction, as well as to determine the risk factors of each one of them. To study the morphologic aspects of the thrombus and its relation with systemic embolism. CONCEPTION AND POPULATION: 1505 consecutive patients with acute myocardial infarction from six Iberian Hospital Coronary Care Units--five from Spain and one from Portugal--were studied. All protocols included a clinical evaluation and a M-mode and 2D echocardiographic study at days 1, 3, 7 at hospital discharge, as well as at months 1, 3, 6, 12, and 24 of the follow-up. In the intraventricular thrombus evaluation just the III and IV Asinger grades were considered. RESULTS: From the total studied patients an echocardiographic study of good quality for thrombus evaluation was found in 1360, and 305 (22.3%) of these had a left ventricular thrombus. In anterior infarctions the incidence of thrombus was 39.9%, and in the other localizations was 11.2%. In what concerns the thrombus morphologic aspects, we found a small thrombus (less than 4 cm2) in 71% of the cases, and a big one (greater than or equal to 4 cm2) in 29%; the shape was laminar in 53.6%, protuberant in 41.7% and pediculated in 4.6%; the outline was smooth in 56.7% and irregular in 43.3%; the echodensity was considered homogeneous in 60.1% heterogeneous in 37.6% and cavitated in 3.3%. Of the several parameters evaluated the following were correlated with left intraventricular thrombosis: anterior localization of the infarction, left ventricular failure, ventricular aneurysm, post infarction angina, bundle branche block and no thrombolytic therapy. The incidence of systemic embolism in a mean follow-up of 290 days was 3.96%, being maximum in the first month (3.4%), but an embolic episode still occurred in the following months in 3.02% of the cases. Systemic embolism correlated with left ventricular thrombus, the pediculated shape and the big size of it, as well as with the oldest patients. CONCLUSIONS: A high incidence of left intraventricular thrombosis after acute myocardial infarction correspond to a low incidence of systemic embolism. Some parameters correlated with intraventricular thrombus or with embolism, what allowed us to consider them as risk factors of these clinical entities. PMID- 1910877 TI - Decrease in pulmonary artery pressure with slow release nifedipine in Saudi patients with primary pulmonary hypertension. AB - We studied the acute and short-term hemodynamic effects of vasodilators in three Saudi patients with primary pulmonary hypertension. The study protocol included the measurement of pulmonary artery pressure, resistance and cardiac output at baseline and at 15, 30, 45 and 60 minutes after 10 mg sublingual nifedipine. These hemodynamic studies repeated at 3 and 6 months follow-up. A 24 hour profile of pulmonary artery and aortic pressures were recorded to evaluate the effect of 20 mg of slow release nifedipine, after 25 mg of captopril and 5 mg of sublingual isordil. After nifedipine there was a marked reduction in systolic pulmonary artery pressure from 85 +/- 18 to 55 +/- 8 mmHg and the pulmonary resistance decreased from 1422 +/- 367 to 954 +/- 69 dynes-sec/cm-5. The cardiac output increased from 2.9 +/- 0.2 to 0.2 to 4.0 +/- 0.4 l/min after nifedipine. The patients were discharged on nifedipine 10 mg qid, except for patient #3 who was a non-responder. At follow-up there was a symptomatic improvement and a favourable hemodynamic response was maintained, though patient #2 required a higher dose of nifedipine. The pulmonary artery 24 hour pressure profile revealed that 20 mg slow release adalat reduced pulmonary artery pressure for a 6 hour period. Whereas, regular nifedipine decreased pulmonary artery pressure for a period of less than 90 minutes. There was no favourable hemodynamic response to either captopril 25 mg oral of isordil 5 mg administered sublingually. We conclude that slow release nifedipine decreases the pulmonary artery pressure for longer periods compared to regular nifedipine in patients with primary pulmonary hypertension. PMID- 1910878 TI - Mitral balloon valvotomy using the Inoue balloon technique for selected patients with severe pliable rheumatic mitral valve stenosis: immediate and short-term results. AB - We selected 40 patients with severe symptomatic rheumatic mitral stenosis for balloon valvotomy using the Inoue balloon technique. The patients' mean age was 31 +/- 14 years and there were 24 females and 16 males. The patients were selected according to the following echo/Doppler criteria; 1. Severe mitral stenosis, i. e. mitral valve area (MVA) less than 1.1 cm2; 2. pliable anterior mitral valve leaflet; 3. absence of calcification of the mitral commissures and 4. absence of significant subvalvular mitral valve disease (Block echo score less than 8). We failed to cross the mitral valve in three cases and repeat attempts in two patients with higher transeptal puncture was successful. Thirty-nine procedures were technically successful (98%). There were no complications. We used an Inoue balloon size 24-30 mm using echo/Doppler guided stepwise mitral dilatation. After mitral balloon valvotomy, the MVA increased from 0.8 +/- 0.2 to 1.7 +/- 0.5 cm2 (p less than 0.001). Five patients developed mild mitral regurgitation and in one patient the degree of mitral regurgitation increased from mild to moderate. The mean mitral valve area 48 hours after the procedure measured 1.9 +/- 0.4 cm2 (echo/Doppler); one patient (2.5%) had residual mitral stenosis (MVA less than 1.5 cm2). At six weeks follow-up study the mean mitral valve area was 1.9 +/- 0.5 cm2 (Echo/Doppler), with no restenosis. We conclude that in selected cases of severe pliable mitral stenosis, the Inoue balloon technique achieves a greater than 100% increase of the MVA, without inducing significant iatrogenic mitral regurgitation or residual stenosis. PMID- 1910879 TI - [Arrhythmic profiles evaluated by Holter's technique in sick sinus syndrome]. AB - OBJECTIVES: The aim of this study was to evaluate in a group of patients with sick sinus syndrome: 1) Characteristics of arrhythmia on Holter monitoring. 2) Value of Holter monitoring to select patients for pacemaker implantation. SETTING: Department of Cardiology in a Central Hospital. METHODS: In 40 patients (27 men and 13 women, aged 37 to 83 years) Holter monitoring during a 24-hour period was performed. According to the arrhythmia profiles four groups of patients were considered: group A--with severe sinus bradycardia; group B--with sinus bradycardia associated to sinoatrial exit block or to sinus pauses; group C -characterized by the bradycardia-tachycardia syndrome and group D--defined by the finding of atrial fibrillation with a slow ventricular response. Symptoms and the presence of structural heart disease were evaluated. RESULTS: In this patients population, 24 patients had coronary artery disease and/or hypertensive heart disease. A severe sinus bradycardia was found in 14 patients (group A) and in other 11 patients it was accompanied by sinoatrial exist block of sinus pauses (group B); 12 patients had the bradycardia-tachycardia syndrome (group C) and periods of atrial fibrillation with a slow ventricular response were found in 3 other patients (Group D). Nonspecific clinical pattern was observed in this population. CONCLUSIONS: Holter monitoring was important to the diagnosis of sick sinus syndrome and for posterior definitive pacemaker implantation. Coronary artery disease and/or hypertensive heart disease were the main pathologies found in this study, being the severe sinus bradycardia and the bradycardia-tachycardia syndrome the principal manifestations of the sick sinus syndrome. PMID- 1910881 TI - Percutaneous mitral balloon valvotomy in pregnancy using the Inoue balloon technique. AB - We describe a 40-year-old female who was 27 weeks pregnant and had severe rheumatic mitral valve stenosis. The patient presented with severe biventricular heart failure and fast atrial fibrillation. Soon after admission the patient sustained a cardiac arrest and was successfully resuscitated. Despite maximal medical therapy the patient was still in pulmonary edema. Beta blockers were contraindicated as the patient had bronchial asthma. Balloon mitral valvotomy using an Inoue 26 mm balloon catheter was done. The procedure was done with pelvic and abdominal shielding. To minimize radiation exposure no angiography was done and the procedure was done with echo-Doppler guided stepwise mitral valve dilatation. The mitral valve area after balloon valvotomy increased from 0.9 to 2 cm2. The total fluoroscopy time was 14 minutes. At 6-week follow-up the patient was virtually asymptomatic. Vaginal delivery was uneventful. Balloon mitral valvotomy using the Inoue technique in pregnancy with echo guided stepwise dilatation is accomplished with minimal radiation exposure, provided abdominal shielding is implemented throughout the procedure. PMID- 1910880 TI - [Regurgitation jets in mitral prosthesis studied using transesophageal echocardiography]. AB - STUDY OBJECTIVE: To analyze the regurgitant jets of mitral valve prostheses studied by transesophageal echocardiography. DESIGN: Prospective study of patients with mitral prostheses with or without suspicion of dysfunction. SETTING: Patients referred to the Echocardiology Department of the Instituto de Cardiologia in Madrid, some as outpatients. PATIENTS AND INTERVENTIONS: Twenty five patients with mitral valve prostheses (5 biological, 7 St Jude, 12 Bjork Shiley and 1 Hall Kaster). Ten male patients and fifteen female, mean age 50 years. Five also had aortic valve prostheses. In only 5 there was a suspicion of dysfunction. The transthoracic echos were done with phased array transducers and the transthoracic with 2.5 (18 patients) or 5 MHz (7 patients) transducers coupled to a commercial echocardiographer. The presence of regurgitant jets was looked for, as well as their origin, maximal area and length, their type and degree of turbulence. MAIN RESULTS: Only 3 mitral regurgitations were noticed by transthoracic echocardiography. All the mechanical prostheses and 80% of the biological ones had regurgitant jets by transesophageal echocardiography. The tilting disc prostheses had two physiological jets, the St. Jude 2, 3, or exceptionally only one central jet. The biological prostheses had one central regurgitant jet, that was smaller than those from the mechanical prostheses (p less than 0.05). There were ten malfunctioning prostheses (5 Bjork Shiley, 3 St Jude and 2 biological). The diagnosis of dysfunction was based on the abnormal origin of the jet (9 cases) or just simply on the characteristics of the regurgitation (turbulence). Four patients were submitted to surgery, all with dysfunctioning prostheses. CONCLUSIONS: Transthoracic echocardiography has a low sensitivity for detecting the regurgitant jets of mitral prostheses. All mechanical prostheses and 80% of biological ones have regurgitation by transesophageal echocardiography. The area and length of the jets are not so different between normal and malfunctioning prostheses in order to separate them. The abnormal jets are recognised because of their abnormal origin and/or their characteristics, with formation of mosaic in color coded Doppler echocardiography. PMID- 1910882 TI - [Intraventricular thrombosis after acute myocardial infarct]. PMID- 1910884 TI - Lack of correspondence among measures identifying the obese. AB - Correspondence among eight measures commonly used to identify the obese was investigated in 225 men and 212 women 18-59 years of age. Measures included weight, body mass index (BMI), relative weight, skinfold thicknesses at triceps and subscapular sites, the sum of four skinfolds, percentage body fat (%BF) determined hydrostatically, and total weight of fat. Intercorrelations within various measures of body mass and total fat are high (0.86-0.99), while correlations between the two skinfolds, and among measures of body mass, subcutaneous fatness, and total body fat are much lower (0.57-0.70). The amount of variation in %BF accounted for by correlations with the other individual measures of obesity (other than fat weight) ranges from 32% to 48%. When analyzed categorically, the upper quintiles of the various measures poorly identify the same individuals as the fattest. The median chance-adjusted correspondences were 0.57 and 0.64 for men and women, respectively, with single values as low as 0.40. Analyses of variance (ANOVA) indicate the misclassification occurring among upper quintiles is nonrandom with respect to mean levels of these obesity measures. We find a considerable lack of correspondence among measures commonly used to identify the obese. This lack of correspondence may lead to unanticipated dissimilarity among people variously classified as obese and to bias regarding risks of associated disease or mortality. PMID- 1910883 TI - Women intending to breastfeed: predictors of early infant feeding experiences. AB - We conducted interviews prenatally and postpartum with 187 women, all of whom intended to breastfeed their newborns. However, 18% of these women either never initiated breastfeeding or stopped within one week. Among women who initiated breastfeeding, we identified four variables as significant predictors of failure to breastfeed for more than seven days: lower confidence in ability to breastfeed, less certainty in the decision to breastfeed, delayed first breastfeeding experience, and lack of rooming in with the baby. Results of this study suggest that women at high risk for not implementing their prenatal breastfeeding intention can be identified for additional support; interventions should focus on prenatal confidence building, early and continuing contact with the newborn, anticipatory guidance prior to discharge, and early pediatric follow up. PMID- 1910885 TI - Fatal motor vehicle traffic accidents among Native Americans. AB - An atypical number of motor vehicle-related deaths has been observed among Native American populations. Little is known about why Native groups exhibit increased mortality from this cause. To better understand factors influencing these occurrences, I examined fatal motor vehicle traffic accidents between 1980 and 1986 involving persons of Native American descent in New York State, exclusive of New York City. Data were obtained from a review of death certificates and coroner reports. Fatal motor vehicle collisions among Native Americans generally occurred among men (74%), in rural areas (55%), between 9:00 p.m. and 3:00 a.m. (62%), and during weekends (78%). A sizable percentage of motor vehicle deaths resulted from collisions with pedestrians (28%). Death frequently occurred before the accident victim reached a hospital (74%). Median age at death for male victims was eight years greater than for female victims. These data suggest the need for immediate efforts focusing on primary prevention to minimize risk-taking behaviors likely to result in motor vehicle accidents. I discuss behavioral and environmental factors influencing these observations. PMID- 1910886 TI - Guidelines for community-based screening for chronic health conditions. AB - Preventive measures for many chronic diseases depend upon identification of asymptomatic individuals who have the disease or who may be at risk for developing it. A screening biochemical test can identify such individuals. Mass screening for biochemical markers or risk factors for chronic conditions, especially for elevated serum cholesterol and blood glucose, has been advocated in recent years and has become increasingly common in various nonmedical community settings. Although generally well intentioned, such programs may fall short of their goals and may even be counterproductive. In recognition of the use of biochemical screening in nonmedical community settings, and in an attempt to make such efforts as productive as possible, the California Department of Health Services (CDHS) has developed state guidelines for these screening programs. These guidelines make recommendations regarding: (1) the criteria for judging the effectiveness of biochemical screening tests; (2) the qualifications and training of screening program staff; (3) the proper use and maintenance of equipment used in screening programs and other quality control measures; (4) referral procedures for persons with abnormal test results; and (5) the lawful implementation of screening programs. Optimally, as pointed out by these guidelines, all community based screening programs should complement a larger health education or risk reduction program that guarantees appropriate medical follow-up and management. Preventive medicine practitioners and organizations embarking on such activities should be familiar with the issues addressed by these guidelines and may find adherence to them useful in developing effective community screening programs. PMID- 1910887 TI - Teaching clinical epidemiology to medical students using a collaborative learning model. AB - Epidemiology and biostatistics are difficult to teach in medical school. To determine the feasibility of applying a collaborative learning model, we randomly assigned one section of an epidemiology and biostatistics class to use this teaching model. Students in this section did not attend lectures or follow the regular curriculum but instead learned epidemiologic concepts by identifying clinical problems of interest to them and reviewing relevant journal articles, with the group leader functioning as facilitator. All students took an identical examination and anonymously evaluated the course. Examination performance was comparable between the study group (mean 72.1%) and the other students (mean 73.5%). However, the students' evaluation of the study group method was more favorable, especially in their perceived mastery of specific cognitive skills. The data suggest that this model can be successfully applied in teaching epidemiology and biostatistics to medical students. PMID- 1910888 TI - Preventive medicine, public health, and the environmental movement. PMID- 1910889 TI - Preventive medicine practitioners and residents: the ties that bind. PMID- 1910890 TI - Why do some women get regular mammograms? AB - One in nine American women will be diagnosed with breast cancer at some time in their lives. Although mammography is a proven technology for diagnosing early, curable breast cancer, most women do not obtain regular mammograms. The purpose of this study was to identify the characteristics of women who received more than one mammogram. Such information is needed to develop health education programs aimed at fostering adherence to routine mammographic screening. The data were obtained from a 1989 random telephone survey of 910 women 50-74 years of age. The survey is part of the evaluation strategy for a five-year breast screening study. Two-thirds of the respondents reported having had mammograms. Most of these women had one or two mammograms. We report two logistic regression models which describe women who had mammograms in the past year and those who had one versus two or more mammograms. The most important variable in the models was physician support. Other consistently significant variables included being willing to pay $75-$100 (although most women did not pay this amount), visiting the doctor at least annually when healthy, being a nonsmoker, and recognizing that women older than 50 are at greater risk for breast cancer. The results indicate that two pronged educational strategies aimed at both women and their physicians are needed to increase the percentage of women who obtain regular mammograms. PMID- 1910891 TI - Improving colorectal cancer screening in a medical residents' primary care clinic. AB - Colorectal cancer is a major cause of morbidity and mortality in the United States. Despite the availability of methods for early detection of this cancer, compliance with published screening guidelines is poor. We began a study using a pretest/posttest design to determine the effectiveness of several methods of improving colorectal cancer screening in an internal medicine residents' Veterans' Administration (VA) Primary Care Clinic. The interventions varied by day of the week and included (1) distributing self-administered Hemoccult II slide kits to patients at clinic registration; (2) conducting an education session for house staff on colorectal cancer screening; and (3) placing reminder cards on patients' medical records. Preintervention rates of compliance with age related screening guidelines recorded in the medical record within the past year were digital rectal examination, 70%; one-time fecal occult blood test, 59%; three-day fecal occult blood test, 1%; and screening sigmoidoscopy (at any time in the past), 5%. No change in physician-performed examinations was seen in any group approximately six weeks after the interventions. However, systematic distribution of Hemoccult II kits resulted in a dramatic increase in screening through this method, to 56.8% (P less than .001). In this setting, physician education and reminders may be insufficient to improve colorectal cancer screening. We discuss possible explanations for this finding, including the high preintervention screening levels and the perception of an already overburdened system. Patient involvement in screening and mechanisms built into the clinic operation may be more successful. PMID- 1910893 TI - Correlates of expected success at health habit change and its role as a predictor in health behavior research. AB - Perceived ability to change health habits successfully is undoubtedly an important factor underlying personal health behavior. This report examines expected success in changing future habits, using a sample of community-resident adults 18-65 years of age (n = 1,367). One set of analyses used expected success as a dependent variable, whereas another set used it as an independent variable for health behavior and knowledge indices. In the dependent variable analysis, results showed that reported past success at health habit change was the strongest predictor of success expected in the future. Optimism about future success was also associated with variables that already placed individuals at an advantage to change behavior (e.g., not smoking, regular exercise, lower Body Mass Index, support in the family). When used as a predictor variable, expected future success was not associated with five health-related, self-report indices of behavior, knowledge, and perceived risk. Further examination showed, however, that in three instances the association between expected success and the outcome indices seemed to plateau in the most optimistic group. Extreme optimism (that admits no chance of failure) may be a belief characteristic that deserves further investigation, one that will present a challenge to research and practice. Men tended to report greater expected future success than women, although women had more favorable reports on three of the five health-related behavior/knowledge indices. PMID- 1910892 TI - Use of educational resources for cardiovascular risk reduction in the Stanford Five-City Project. AB - To investigate the extent to which individuals use health education resources for cardiovascular risk reduction, we conducted a cross-sectional survey of 2,234 adults 18-74 years of age in four northern California cities. The purposes of the study were to (1) assess the use of 10 cardiovascular disease (CVD) intervention materials and programs, (2) compare use rates between the treatment and control communities of the Stanford Five-City Project, and (3) examine variation in use by type of intervention, risk factor, and sociodemographic status. The community level analyses indicate that up to one-third of adults had used interventions to modify CVD risk factors during a one-year period, and that communities with comprehensive risk reduction programs had higher rates of use, particularly for printed education materials. The subgroup analyses indicate substantial variability in use depending on sociodemographic status, with those at highest risk (men, older adults, and low socioeconomic groups) reporting the lowest use of CVD intervention materials and programs. PMID- 1910894 TI - Patients' perspectives of a physician-delivered smoking cessation intervention. AB - Forty-three patients--recipients of a highly structured, physician-delivered smoking cessation intervention--were interviewed using ethnographic (anthropological) research methods. We conducted interviews with patients after visits with the physician, then audiotaped and transcribed them. Discourse analysis of interview texts identified features and components of the physician maneuver most effective from the patients' point of view. Patients discussed two general areas of physicians' preventive activities: an interventionistic component (in which professional, diagnostic, and authoritative features were emphasized) and a personalistic component (in which physicians were experienced as equals, supportive, caring, empowering, and challenging). From the perspective of patients, the personalistic component of the physician-delivered smoking cessation maneuver appeared most effective. We conclude that, in clinical preventive medicine generally, patients (1) evaluate the kind of support they receive from their physician (e.g., degree of empathy, encouragement, and sincerity), (2) respond favorably to positive imagery in the challenge to alter their lifestyle, (3) look for a balance in the relationship established with their physician (negotiation, respect, mutual understanding, and rapport), and (4) remember the consistency and regularity of their physician's health promotion messages. PMID- 1910895 TI - Rhinology. Index to volumes 20-28 (years 1982-1990). PMID- 1910896 TI - [Intracardiac closed-heart cryoablation of tachycardia]. PMID- 1910897 TI - [The first experience with surgical treatment of supraventricular tachycardia]. AB - The article analyses the late-term results of operations on 46 patients for paroxysms of supraventricular tachyarrhythmias (SVTA) which were refractory to prophylactic administration of antiarrhythmics. Transvenous electrodestruction of the atrio-ventricular junction were carried out in 39 patients. The results were good in 34 and satisfactory in 3 patients; conductivity and paroxysms reappeared in 2 patients. ++Anti-tachycardial ECS were implanted in 6 patients with good results. One patient underwent electrodestruction of an accessory conduction tract of the type of Kent's bundle with a stable clinical effect. The results of the study provide evidence of the high efficacy of surgical management of complex SVTA in a regional cardiosurgical center. PMID- 1910898 TI - [Reoperations in patients with heart valve prosthesis]. AB - The results of operations performed for the second time on 193 patients with heart valve prostheses are analysed. Prosthesis endocarditis and thrombosis of the prosthesis are the most severe complications of valve replacement. An effective scheme for the performance of repeated operations in these patients is suggested, which was developed at the Bakulev Institute of Cardiovascular Surgery, USSR AMS. The study makes it possible to conclude that the risk of such operations is fully justified. PMID- 1910899 TI - [Carotid sinus syndrome: diagnosis, treatment and complications]. AB - Continuous electrocardiostimulation was applied in 33 patients with the carotid sinus syndrome. Neither fatal outcomes nor complications occurred in the hospital period. Analysis of complications in the late-term period (follow-up from one to 22 months) allowed the conclusion that physiological stimulation of the heart (in the AAI regimen) is the optimal method for the treatment of the cardioinhibitory form of the syndrome. The management of the mixed form is still disputable. PMID- 1910901 TI - [Quantitative analysis of hemodynamic disorders in coronary occlusion based on the roentgeno-cinematographic data]. AB - The contrasting time of the coronary arteries in 4 types of atherosclerotic lesions was determined by means of quantitative analysis of the coronarograms. The contrasting time was found to be dependent both on the degree of the stenosis and on the condition of the distal segment of the coronary artery. The condition of the drainage tracts had a more marked effect on the contrasting time. The coronary arteries contrasting time is considered as an index of peripheral resistance in the studied segment. PMID- 1910900 TI - [Outcomes of reoperations in dysfunction of mechanical prostheses in relation to the clinical course]. AB - Operations were conducted for the second time on 87 patients (98 operations). Reoperations were performed on 75 (76.5%) and closure of the fistula in 23 (23.5%) patients. The outcome of the operation was appraised according to the clinical course: without sepsis and with prosthetic septic endocarditis, respectively, in 57 (65.5%) and 30 (34.5%) cases. It was found that survival was lower among patients with prosthetic septic endocarditis than among those without sepsis, 37.9% and 53%, respectively. The position of the prosthesis determined the time of the development of the complication, both in fistulas and in thromboses. Disturbances in the function of the prosthesis occur mainly in the first postoperative months in patients without sepsis and in the first months and the late-term periods after surgery in patients with prosthetic septic endocarditis. PMID- 1910902 TI - [Current trends in the development of coronary surgery]. AB - The authors conducted a comparative study of various methods of coronary shunting by means of microsurgical techniques in 240 patients who were operated on for ischemic heart disease. Total myocardial revascularization, including arteries measuring less than 1.5 mm in diameter and vessels in the zones of cardiosclerosis, was found to be more effective than the techniques of shunting of only the affected major branches. The advantages of a mammary-coronary shunt over anauto- logous venous shunt in reconstruction of coronary arteries under unfavourable hemodynamic conditions are demonstrated. It is also shown that multiple bi-mammary-coronary shunting of the branches of the left coronary artery is a promising method. PMID- 1910903 TI - [Ultrastructural analysis of myocardial condition during cardioplegic protection in heart valve prosthesis]. AB - The article deals with the results of ultrastructural study of the myocardium at three stages of cardiosurgical operations: preischemic, ischemic, and during reoxygenation. A statistically significant difference was revealed in the condition of the cardiomyocyte organelles in each of these stages, and the degree of their intraoperative destruction was determined. It is concluded that ischemia of more than 90 minutes redoubles the progress of irreparable changes of the cardiomyocytes, particularly in patients with severe damage to the myocardium in the preischemic stage. The search for means of cardioprotection for these patients must be continued. PMID- 1910904 TI - [A method of taking the heart and a block from both lungs of one donor for transplantation to two recipients (experimental study)]. AB - A method allowing a heart and block of two lungs of one donor to be transplanted to two recipients was elaborated on 20 human cadavers. First the heart and then the lung transplants are removed. The main peculiarity of the method consists in optimal separation of the left atrial wall between the donor's heart and the block of two lungs. A method for the formation of a cuff of the left atrium which makes inspection and orientation in the anatomical structures easier is suggested. PMID- 1910905 TI - [The role of electrocardiographic examination in the complex evaluation of potential heart donors]. AB - From October, 1986 to February, 1990 eighty-five potential donors with death of the brain were examined at the Scientific Research Institute of Transplantology and Artificial Organs, USSR Ministry of Public Health. Thirty of them were used as heart donors in orthotopic transplantation of the heart; 24 (80%) were males and 6 (20%) females. The cause of death of the brain was craniocerebral trauma in 13, brain tumor in 9, hemorrhage into the brain tissue in 7 cases, and gunshot injury to the skull with damage to the brain in one case. In appraisal of the donors; in 8 (26.7%) cases the ECG did not differ from the initial one, in another 8 cases (26.7%) the ECG demonstrated electrolyte disorders in the form of hypokalemia , still in another 8 cases right bundle-branch block was encountered, in 2 (6.65%) the ECG showed transient form of cardiac fibrillation, in still another 2 cases I-II degree atrioventricular block was found, in one (3.3%) right and left bundle-branch block was demonstrated, and in one case the ECG showed diminished nutrition in the region of the posterior left-ventricular wall. All donors had disorders of homeostasis characteristic of patients with death of the brain, while the condition of hemodynamics conformed to these disorders. It is concluded on the basis of the obtained data that electrocardiographic monitoring is expedient and that it plays a role in complex appraisal of a potential heart donor. PMID- 1910906 TI - [Postponed closure of the sternum after operations on the heart with extracorporeal circulation]. AB - Data on postponed closure of the sternum in 3 patients who were operated on with extracorporeal circulation are discussed. Various clinical and technical aspects of the applied method are considered. On the basis of their personal experience and the literature data, the authors discuss the causes of the development of acute heart dilatation in operations with extracorporeal circulation and, with due regard for this, substantiate the indications for the use of the method. Postponed closure of the sternum is a promising method of treatment of critical hemodynamic disorders which occur at the stage of closure of the sternotomy and are characterized by the picture of cardiac tamponade. PMID- 1910907 TI - [Pulmonary sequestration]. AB - The author discusses pulmonary sequestration which is a rare developmental anomaly difficult for diagnosis. Eleven patients were under observation and underwent operation for pulmonary sequestration (8 with intralobar and 3 with extralobar) which accounted for 2.4% of patients with congenital developmental anomalies of the lungs and for 0.48% of those with chronic unspecific disease of the lung. Complete clinical radiological examination, including aortography, made it possible to recognize the anomaly before the operation in 6 patients. In the remaining patients sequestration of the pulmonary tissue was an operative finding. Preoperative functional study of pulmonary circulation revealed a marked left-to-right shunt of the blood, increased oxygenation of blood in the superior vena cava and saturation of arterial and venous blood with oxygen (to 94 and 91%, respectively, on the average). Analysis of clinical, radiological, and morphological data allowed three main forms of pulmonary sequestration to be distinguished: cystic-abscessed, pseudotumorous, and fibrous-atelectatic. PMID- 1910908 TI - [Endoscopic laser surgery of the trachea]. AB - Bronchoscopic laser operative interventions with the use of yttrium- aluminum garnet laser were carried out in 36 patients with various pathological structures of the trachea. Laser endosurgery was applied as radical and palliative types of therapy. Endoscopic laser interventions make it possible to remove completely benign and carcinoid tumors, correct some types of cicatricial stenoses, restore continuity of the trachea, and remove respiratory insufficiency in inoperable malignant neoplasms with exophytic growth. PMID- 1910909 TI - [Various clinical and roentgenological aspects of diagnosis of postoperative empyema in pulmonary surgery]. AB - The results of a 10-year follow-up of 101 patients with pyothorax that developed after operations on the lungs, bronchi, and trachea (5.4% of all patients who underwent operation) show a stable fever of 38 degrees C and higher, pain in the chest, leucocytosis, and a shift of the peripheral blood leucocyte count to the left to be the most constant clinical signs of suppuration of the pleura in the postoperative period. Experience convinces the authors that the initial radiological signs of pyothorax are early fragmentation of the pleural cavity after pneumonectomy and a rigid residual pleural cavity after partial lung resection. Computed tomography complements the classical radiological examination and is conductive to timely diagnosis and successful treatment of postoperative pyothorax. PMID- 1910910 TI - [Doppler echocardiography in the evaluation of hemodynamics in children with bilateral forms of chronic nonspecific inflammatory lung diseases]. PMID- 1910911 TI - [Clinical aspects, diagnosis and treatment of esophageal spasm]. AB - Esophageal spasm Teschendorf 's syndrome) is rarely distinguished among neuromuscular diseases of the esophagus, which leads to improper treatment. Primary esophageal spasm and secondary esophageal spasm should be distinguished, the latter developing in cardiospasm or achylia of the cardia. Retrosternal pain and dysphagia prevail in the clinical picture of ++esophageal spasm . X-ray and esophagomanometry are the most informative among the objective methods of examination. In a group of 106 patients 49 had primary and 57 had secondary esophageal spasm . A complex of measures should be applied in the management of esophageal spasm+. Primary esophageal spasm is treated only by nonoperative measures (spasmolytics, tranquilizers, vitamins, acupuncture reflex therapy and psychotherapy according to a suggested scheme), a course of pneumocardiodilatation (no more than 5 sessions) is included in the management of secondary esophageal spasm+. Such treatment produced good and satisfactory results in 100% of patients with primary and in 72% of patients with secondary esophagitis. The management of secondary esophagitis is a more difficult problem which calls for further study. PMID- 1910912 TI - [A case of rare dysfunction of xenopericardial bioprosthesis in the mitral position]. PMID- 1910913 TI - [Indications for aortocoronary shunting in relation to ejection fraction and segmental activity of the left ventricle (data of the coronarography, ventriculography and intra-cardiac hemodynamics)]. AB - The left-ventricular ejection fraction, reflecting the contractile capacity of the myocardium according to the clinical data, is the most objective criterion in indication for the operation for aortocoronary shunting. The indices of central hemodynamics appearing in response to the exercise test during intracardiac catheterization of the right heart and monitor-computer control with mathematical analysis were used in objective appraisal of the left-ventricular ejection fraction in selecting for surgical treatment patients suffering from ischemic heart disease with normal and reduced ejection fraction of the left ventricle. Two gradations of patients with ischemic heart disease were set apart during the hemodynamic exercise test: the first--patients with a high and effective chronotropic reserve--subgroup I("+X") and the second--patients with a poor and ineffective chronotropic reserve--subgroup II("--X"). It was found that in a single-valued left-ventricular ejection fraction (normal or low) in patients with ischemic heart disease there may be the presence or absence of latent cardiac insufficiency according to the results of the hemodynamic exercise test which must be determined in indications for surgical treatment. PMID- 1910914 TI - [Adaptation mechanisms to the short intestine. Influence of the biliopancreatic factor: experimental study]. AB - Massive small bowel resection that results in short bowel syndrome brings about regulatory mechanisms in the remaining intestine aimed at preventing the ensuing malabsorption. The purpose of the present study was to determine the role of pancreatic and biliary secretions in intestinal adaptation after small bowel resection. To do so, both pancreatic and biliary fluids were prevented from reaching the lumen of most of the small bowel. Four groups of animals were prepared: I) control group; II) eighty percent small bowel resection; III) duodenoileal by-pass; and IV) duodenoileal by-pass plus small bowel resection. After a fifteen days recovery period, the following were recorded: animal weight; plasma protein, BUN, cholesterol, glucose, and Ca++; the length and diameter of the jejunum and ileum, the height of the mucosal layer, and microvilli density. Intestinal adaptation was excellent in animals after small bowel resection. All animals in group IV died due to severe malabsorption. Diversion of pancreatic and biliary juice in animals with duodenoileal by-pass did not prevent intestinal adaptation. We conclude that the effect of pancreatic and biliary juice on intestinal adaptation is additive to that of other putative hormonal mechanisms. PMID- 1910916 TI - [Hepatic trauma (90 consecutive cases treated in 9 years]. AB - 90 consecutive hepatic traumatisms at the Hospital de Navarra are presented over a period of 9 years, excluding those which did not overcome the initial reanimation phase and those diagnosed as necropsy. The etiology is presented (76 closed and 14 open), the degree of lesion, associated intra and extra-abdominal lesions plus the results (12.2% mortality) and causes of death related to the degree of lesion and associated lesion. Finally, our casuistics and results are compared with those appearing in the existing bibliography on the subject. PMID- 1910915 TI - [Gammagraphy with labeled leukocytes as an activity and extension index of Crohn disease]. AB - The knowledge of the location and extent of bowel involment and disease activity can be an important aspect on the evaluation of inflammatory bowel disease. Thirty five patients of Crohn's disease (CD) have been studied in this sense. We performed a total of 44 scintigraphic examinations using 99mTc-HMPAO labeled leukocytes and the results were compared with several clinical-biological indexes and with radiology and endoscopy. The Tc scan was the most sensitive (84.3%) and specific (100%) activity index and showed an excellent correlation with radiology and/or endoscopy in the assessment of extent of disease. Leukocyte scanning brought useful information for the management of stenosis in CD. PMID- 1910917 TI - [Precancerous lesions of gastric cancer (I): incidence in 2 population groups: symptomatic and asymptomatic]. AB - We analyzed 850 gastric biopsy specimens: 643 were obtained from patients with gastric symptoms, and 207 from apparently normal individuals. We evaluated the incidence of precancerous lesions (PL) of the stomach (chronic atrophic gastritis, intestinal metaplasia and gastric dysplasia) in both groups of patients (symptomatic and assymptomatic). We also studied the relationship between these lesions and diverse clinical and morphological parameters (age, sex, location and endoscopic findings). Our results indicate a higher incidence than expected of PL in an area of low risk of the gastric cancer, both in symptomatic patients (CAG: 65%, IM: 50% and GD: 23%) and in the normal population (CAG: 24%, IM: 17.4% and GD: 2%). These lesions were preferentially located in the antral region and the antro-corporal transitional zone. The incidence of the PL was highest in patients 50 and 60 years of age. These parameters should be considered as risk factors in the development of a gastric carcinoma of the intestinal type. PMID- 1910918 TI - [Surgical complications of endoscopic sphincterotomy]. AB - Between June 1988 and June 1990, 267 endoscopic sphincterotomies were attempted for various indications. In 204 patients (74%) the indication was choledocholithiasis of which 109 with an intact gallbladder. Of the 267 patients, 22 (8.2%) developed complications and 4 died (1.4%). Six required urgent surgery 2.24% of the entire series and 0.3% of all emergency surgery done in that period in our department. Although most complications can be treated medically, about one fourth require emergency surgery. A medico-surgical team is needed to manage this type of patient. PMID- 1910919 TI - [Hemodynamic changes in an acute pancreatitis experimental model in awaken rats]. AB - The aim of the present study was to determine the hemodynamic effect of acute hemorrhagic pancreatitis in conscious rats. For this purpose, radioactive microspheres were used in 3 groups: control (n = 5); 25 min pancreatitis (n = 10); 50 min pancreatitis (n = 10), performing a basal and final (25 or 50 minutes postpancreatitis) hemodynamic study. Acute hemorrhagic pancreatitis was induced in 25 min and 50 min pancreatitis groups overwhelming shock with decrease of 55% in cardiac output, 58% in renal blood flow while total peripheral resistance increased in 342%. No changes were registered the in control group. PMID- 1910920 TI - [Gastroesophageal reflux and esophagitis (II). Treatment guidelines]. AB - The current therapeutic approach to gastroesophageal reflux disease is reviewed. Dietary measures, postural measures and drug therapy can be used to alleviate symptoms and for improving healing of esophageal lesions. Surgery can be used only in a few cases. Antacids, alginic acid, and motor-stimulating drugs i.e. metoclopramide and bethanecol, may be sufficient to treat pathologic reflux without esophagitis. When erosive or ulcerative lesions, a more vigorous treatment including H2 receptor blockers and omeprazole can be used. PMID- 1910921 TI - [Solid and papillary tumor on ectopic pancreas in transversal mesocolon]. AB - A solid and papillary neoplasm of a mesocolonic ectopic pancreas, 6 cm of diameter, was found by chance in a woman age 33 and resected surgically. The histologic study showed a well delimited tumor made up of uniform eosinophilic cells forming papillae, with solid and cystics areas. Pancreatic tissue was detected in the periphery of the neoplasm. The presence of ectopic pancreas with a solid and papillary tumor is extremely rare. We have only found one case in the literature (5). PMID- 1910922 TI - [Variceal hemorrhage on the colostomy area in a patient with portal hypertension]. AB - A 68 years old patient who had a colostomy done for an abdomino-perineal resection, started episodes of bleeding seven years later from varices at the colostomy site secondary to portal hypertension. Direct suture of the varices and distal colonic resection were ineffective to stop the bleeding. Sclerotherapy with polidocanol, however permitted the patient to remain asymptomatic during 14 months. PMID- 1910923 TI - [Computed axial tomographic image of an inflammatory fibroid polyp]. PMID- 1910924 TI - [Severe occurrence of idiopathic ulcerative colitis caused by Aeromonas sobria]. PMID- 1910925 TI - [Helicobacter pylori and duodenal ulcer treated with omeprazole]. PMID- 1910926 TI - [Foreign body in rectosigmoid]. PMID- 1910927 TI - [Duchenne muscular dystrophy]. PMID- 1910928 TI - [Clinical diagnosis of Duchenne muscular dystrophy using anti-dystrophin antibodies]. PMID- 1910929 TI - [Genetic counselling for Duchenne muscular dystrophy]. PMID- 1910930 TI - [Progress in clinical management and prognosis of Duchenne muscular dystrophy]. PMID- 1910931 TI - [Dynamics of extracellular acetylcholine of the gerbil striatum during cerebral ischemia monitored by intracerebral microdialysis]. AB - Neurons in the hippocampus and striatum are vulnerable to the ischemic insult. In the present study we focused on the vulnerability of acetylcholine (ACh) containing neurons in the striatum. To determine the change of ACh content in the striatum, we employed a simple sensitive brain microdialysis method with high performance liquid chromatography electrochemical detection. Morphological change of cholinergic neurons was studied by ACh-esterase staining during ischemic insult. After bilateral carotid artery occlusion, local cerebral flow decreased less than 5 ml/min/100 g in the striatum. Ach content in dialysate for 20 min after the occlusion was elevated to 135% of the control. ACh content decreased to 15% of the control 2hs after the ischemia. Density of Cholinergic fibers and cell bodies was reduced 10 min after the ischemia and further decreased 20 min after the occlusion. Our study suggests that the transient elevation of ACh content was probably due to diffusion of ACh from destruction cholinergic terminals after the ischemic insult. The increase of ACh immediately after arterial occlusion may affect severity of ischemic damage in the brain by its excitatory effect. PMID- 1910932 TI - [Relationship between cardiovascular circulation and intracranial pressure- analyses of polygraphic recordings during cardiac surgery in congenital heart diseases]. AB - Few reports have appeared in regard to cerebral perfusion pressure (CPP) accompanying fluctuations in intracranial pressure (ICP), arterial pressure (BP) and central venous pressure (CVP) as well as autoregulation of cerebral circulation in neonates and infants. Therefore, we report here on interesting findings we obtained from monitoring ICP, BP, and CVP during operations in 30 neonates or infants with congenital heart disease as our subjects. i) ICP fluctuates depending on arterial pressure and venous pressure, but changes in the latter display a clearer effect. ii) On inducing anesthesia the amplitude of ICP pulsating waves became gradually larger, but following intubation intracranial pressure was somewhat reduced and became stable. iii) Following thoracotomy CVP rose and at the same time intracranial pressure also increased somewhat. Before thoracotomy ICP pulsating waves resembled arterial pressure wave forms, but after thoracotomy they resembled central venous pressure wave forms. iv) In cases with two-peak ICP pulsating waves, when we conducted a study by blocking venous return from the internal carotid vein during the operation by the Queckenstedt method, ICP rose by increasing its amplitude, but the pulsating wave forms lost their venous component, and changed into a single peak consisting of an arterial component. v) In order to observe the relationship between changes in arterial pressure and ICP, when we looked at changes in ICP accompanying partial blockage of the descending aorta (DAo), simultaneously with the partial blocking of the DAo both AP and CVP rose, and ICP also rose accordingly. Also, when arterial blockage was relaxed, BP, CVP, and ICP immediately recovered completely to the status quo prior to the blocking procedure. This finding indicates that by blocking of the DAo, intracranial arterial and venous blood volume abruptly rapidly increase and since CVP also rises, therefore ICP rises to maintain a balance with these. As a result, this brings about the effect of normally maintaining the cerebral perfusion volume. vi) If we look at changes in ICP brought about by partial blocking of the ascending aorta, blockage of the artery brought about a further reduction in BP, and in this case since the arterial blood flow into the cranium also fell off markedly, we found that ICP also was reduced. The above results suggest that in the normal brains of neonates and infants even when under various conditions various fluctuations in corporeal circulation develop, cerebral perfusion volume adjusts itself in response to this, and thus autoregulation of cerebral blood flow is able to act in an adequate way. PMID- 1910933 TI - [A case of central pontine myelinolysis with neurological recovery after administration of glucocorticoid]. AB - A survival case of central pontine myelinolysis (CPM) is reported herein with a review of 22 MRI-analyzed CPM survivors in the literature. A 65-year-old male was struck on the forehead while in a traffic accident. He was almost fully conscious and neurologically free on admission. Laboratory data were normal except hyponatremia [122 mEq/l] and hypoproteinemia [5.8 g/dl]. 2 hours later he became drowsy and left hemiparesis. The CT scan showed right frontal cerebral hematoma leading to a remarkable midline shift. Immediately, aspiration of the hematoma was performed. On the next day, he returned to the initial neurological level. On the third day, however, he again became comatose followed by tetraparesis and ataxic respiration. While the CT scan at that time did not display any abnormality in the pons, the severe dysfunction of the brain stem occurred after the correction of hyponatremia strongly suggesting CPM. The serum Na levels were kept between 110 and 125 [mEq/l]. In addition, 375 mg of methylprednisolone had been daily administrated during and after a gradual correction of the hyponatremia, because glucocorticoid proved to be effective in the models of CPM. The neurological condition began to improve on the 14th day after admission. Eventually, he became conscious and independent in his daily activities, the time span being 8 months after the trauma. The trident MRI lesion in the basis pontis was 5 mm in diameter and much smaller than clinically expected. The 23 MRI analyzed CPM survivors were reviewed in the literature including the present case. There were 7 males and 16 females, with a mean age of 48.5 years.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1910934 TI - [Massive osteolysis of the skull--case report and review of the literature]. AB - The authors describe a rare case of massive osteolysis of the skull, along with a brief review of the literature. A 11 year-old female was admitted with a complaint of a painless depression in the right parietal region, which had been slowly enlarging for several years. Skull x-ray films revealed a radiolucent area with irregular and non-sclerotic margin in the right parietal bone. Plain CT showed an osteolytic lesion involving the outer table and diploe with absence of new bone formation. On 99mTc scintigrams, there were no abnormal accumulation in the whole skeletal system including the skull. Blood examinations including serum calcium, phosphate, and alkaline phosphatase were entirely normal. In the differential diagnosis of lytic skull lesion, the long, inactive course without any corroborative local or systemic evidence of illness, and the absence of new bone formation on radiological examinations clinch the diagnosis of massive osteolysis. PMID- 1910935 TI - [Advances in myoclonus research]. PMID- 1910936 TI - [Dysraphism]. PMID- 1910937 TI - [Evaluation of SPECT with N-isopropyl [I-123]-p-iodoamphetamine (IMP) or technetium-99m [99mTc]-d,l-hexamethylpropyleneamine oxime (d, 1-HM-PAO) in cerebral concussion]. AB - 123I-IMP and Tc-PAO SPECT were performed in 20 cases of cerebral concussion ranging in age from 4 to 20 years old, including six cases of the juvenile head trauma syndrome (JHTS). The SPECT findings were divided into two main types: six cases in the normal group with no blood flow abnormalities, and 14 cases in abnormal group showing reduced blood flow, mainly in cerebellum and occipital lobe except in one case. In 10 cases with reduced blood flow which could be analyzed, calculation of the blood flow ratio in the temporal and occipital lobes and the cerebellum with the frontal lobe taken as 100 showed values of 93.5% for the temporal lobe, 82.7% for the occipital lobe and 76.8% for the cerebellum. A statistically significant reduction in blood flow occurred in the occipital lobe and cerebellum. In blood examination, abnormally high values of white blood cell counts were observed transiently in 94% of cerebral concussion cases. Abnormalities in brain stem and hypothalamus appeared to cause these abnormal WBC values. From these findings, it was suggested that the blood flow regions of the basilar and posterior cerebral arteries, i.e., the brain stem and hypothalamus are closely connected with the lesions responsible for cerebral concussion. It also appeared that the JHTS occurs in cerebral concussion cases where recovery of the abnormal blood flow in these regions in poor. PMID- 1910938 TI - [Ultrastructural findings of arachnoid cysts and epithelial cysts]. AB - There may be several kinds of pathological conditions in the cystic lesion which are clinically diagnosed as benign intracranial cysts on CT scan. Light and electron microscopic studies on cyst walls were important in the differential diagnosis of benign intracranial cysts. We have studied 5 cases of intracranial arachnoid cysts and two epithelial cysts using the light and electron microscopy. Five cases of intracranial arachnoid cysts included two children and three adults (three females and two males). Three cases of them were localized in the middle cranial fossa, one case in the anterior and middle cranial fossa and one case in the lateral ventricle, giving headache and convulsion as the initial complaints. As for the epithelial cysts, one was localized at the para-collicular area complaining enlarged head and swollen anterior fontanelle and the other of four years was located in the fourth ventricle with headache and ataxic gait. On CT all of them demonstrated diffuse low density areas in both the arachnoid and the epithelial cysts without communicating findings between the cystic cavities and subarachnoid space on metrizamide CT cisternography. The arachnoid cyst walls were basically similar in structure to the normal arachnoid membrane and composed of elongated epithelial cells like the arachnoid cell and the connective tissues with lamellar collagen fiber bundles. However, 3 of the 5 cases had only fibrous tissues without epithelial cells. The inner sheath of the arachnoid cyst walls was composed of one or several layers of the arachnoid cells with flattened and relatively electron-dense cytoplasm on electron micrograph. They had a lot of elongated process and were tangled with each other, making large extracellular spaces between them. Below the electron dense arachnoid cells, compact packed cells with interdigitation partly demonstrated intercellular contacts such as numerous desmosomes and tight junctions. In those intercellular spaces collagen fibers and microfibrils were observed. The cells contained abundant cytoplasmic microfibrils and numerous organelles. They were separated from numerous collagen fibers and fibroblasts by non continuous basal lamina under the epithelial cells. Epithelial cyst wall had a layer of cuboidal or columnal epithelium in the inner layer of cyst wall. Those epithelial cells demonstrated granules having positive in PAS and mucicarmine stain in their cytoplasm. On electron microscopical study epithelial cells revealed a lot of microvilli and coating materials on the surface of them without cilia. The basement membranes were well developed under the epithelial cells separated from the connective tissues. In the intercellular clefts of the epithelial cells tight junctions and interdigitations were recognized.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1910939 TI - [Influence of total body hyperthermia on normal brain tissue]. AB - The influence of total body hyperthermia (TBHT) on normal brain tissue was studied in 40 dogs. The dogs were anesthetized with sodium thiopental (10 mg/kg/hr) intravenously, and were ventilated by artificial respirator. The TBHT was induced by extracorporeal circuit in cooperating a heat exchanger. Rectal temperature was raised to 41.5 degrees C and maintained at 41. 5 -42.0 degrees C for 2 hr (HT period) and was then fallen to normothermia by cooling, Regional cerebral blood flow (CBF) was measured by hydrogen clearance method before heating, during and after TBHT treatment. Brain temperature, rectal temperature, intracranial pressure (ICP), brain tissue pH and electroencephalography (EEG) were monitored continuously during TBHT. Histopathological changes of the brain tissue were studied in dogs killed just after TBHT and 2 weeks after TBHT. Autoregulation of the CBF during HT period was assessed by measuring the regional CBF and the ICP at a state of induced hypo- or hypertension. The brain temperature (at the depth of 5mm under the brain surface) was usually 0.6 degrees C lower than the rectal temperature during HT period. The regional CBF increased from 38.1 +/- 6.5 (mean +/- SD) to 49.1 +/- 9.8ml/100 g/min by raising rectal temperature, and it recovered to a normal value after cooling. The ICP increased from 10.3 +/- 4.2 to 16.8 +/- 3.4 mmHg by raising rectal temperature, and it returned to a normal value after cooling. Brain tissue pH decreased from 7.33 +/- 0.02 to 7.17 +/- 0.09 rapidly when the rectal temperature reached 41.0 degrees C, and then returned to a normal value gradually after the start of cooling.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1910940 TI - [Evaluation of magnesium, calcium and aluminum deposition in bone in situ]. AB - Current changing epidemiological pattern in the Western Pacific strongly suggests a contribution of the environmental factors to the pathogenetic process of amyotrophic lateral sclerosis (ALS). As a reflection of excess metals and a deficiency of minerals in soil and water samples in these foci, this study was designed experimentally to evaluate the concentration of calcium (Ca), magnesium (Mg) and aluminum (Al) in the bones of rats fed unbalanced mineral diets. Twenty eight male Wistar rats, weighing 200 g, were fed either a standard diet, a low Ca diet, a low Ca-Mg diet, or a low Ca-Mg diet with high Al for 90 days. The composition of the diet/100 g consists of Ca 1250 mg, Mg 300 mg, Al 10 mg, Zn 4 mg in the standard diet; Ca 3 mg and Mg 2 mg in the low Ca-Mg diet; and Al 194 mg in the high Al diet, Al supplied as Al lactate. Ca, Mg and Al concentrations were determined by using inductively coupled plasma emission spectrometry (ICP) for bone and atomic absorption spectrometry for serum. Serum Ca levels in the groups fed unbalanced mineral diets were lower than those in the group fed standard diet. Serum Mg levels were markedly decreased in the groups fed low Ca-Mg diet and low Ca-Mg plus high Al diet, compared with those in the groups fed standard diet and low Ca diet.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1910941 TI - [Longitudinal change of H-1 spectroscopy in cerebral infarction]. AB - Longitudinal change of the proton spectroscopy was observed in 2 cases of cerebral infarction. Proton spectra was acquired utilizing stimulated echo acquisition mode (STEAM). In acute stage, the increase of lactic acid and decrease of N-acetyl-aspartic acid (NAA) was observed prior to the appearance of abnormality in imagings such as magnetic resonance imaging and computer tomography. The increase of lactic acid was observed in subacute stage and chronic stage (in severe case). The decrease of NAA persisted in chronic stage. The increase of lactic acid and decrease of NAA indicate a damage of the ischemic tissue. The degree of the decrease of the NAA seems to be a reasonable indicator of the viability of the damaged tissue. The proton spectroscopy is a powerful modality for the evaluation of the extent of tissue damage caused by the ischemic insult. PMID- 1910942 TI - [A case of sphenoid ridge meningioma presenting as subarachnoid hemorrhage]. AB - The authors present a case of sphenoid ridge meningioma presenting as subarachnoid hemorrhage. A 56-year-old man came to our hospital with a complaint of severe headache developed during evacuation of the bowels. Computed tomogram on admission revealed a mass lesion of high density, which was homogeneously enhanced with contrast media, in the medial part of the left sphenoid ridge, but no evidence of the intracranial hemorrhage. Nevertheless, the cerebrospinal fluid obtained by lumbar puncture was bloody, indicating the occurrence of subarachnoid hemorrhage. Cerebral angiograms showed no abnormality except for the downward displacement of the suprachnoidal segment of the left internal carotid artery. During the operation, the adhesion between the tumor and the cortical vein was observed and the subarachnoid hemorrhage was recognized exclusively around the vein. These findings indicates that the present hemorrhage may be derived from the vein. In the previous reports of meningioma associated with intracranial hemorrhage, the origin of hemorrhage and the pathophysiological mechanism for hemorrhage have been speculated from both operative and histological findings. In consideration of these speculations, we discussed the possible mechanism for the breakdown of the cortical vein in the present case. PMID- 1910943 TI - [The role of the somatosensory and association cortices in hand function]. PMID- 1910944 TI - [Effects of ONO-1016, inhibitor of C1-/HCO3- exchange, on the brain water content and local cerebral blood flow following cerebral ischemia in spontaneously hypertensive rats]. AB - The effects of ONO-1016, as an inhibitor of C1-/HCO3-exchange, on the brain edema and circulatory failure following cerebral ischemia were examined in stroke-prone spontaneously hypertensive rats (SHR-SP). SHR-SP were divided into three groups: control (sham-operation), non-treated, ONO-1016 group, respectively. Cerebral ischemia was produced by bilateral carotid artery occlusion (BCAO) for 1 hr and then following reperfusion. The brain water content and local cerebral blood flow (LCBF) were determined by dry-wet method and 14C-iodoantipyrine method 2 hr after start of reperfusion. ONO-1016 was given intravenously at a dose of 100 micrograms/kg/min prior to ischemia. The brain water content increased in septum (SP), amygdala (AM) in both non-treated and ONO-1016 groups compared from those in control group. However, brain water contents in SP and midbrain were lower in ONO-1016 group than those in non-treated group. LCBFs decreased to 50-80% in SP, cerebral cortex (CT), striatum (ST), hippocampus (HC) and AM in non-treated group, while LCBFs decreased to 60-80% in SP, CT, ST, AM in ONO-1016 group when compared from those in control group. Decrease of LCBF in ST and HC in ONO-1016 group were less severe than those in non-treated group. From these results, ONO 1016 may prevent the brain edema formation associated with hypoperfusion during reperfusion period after ischemia in SHR-SP. PMID- 1910945 TI - [Somatosensory evoked potential and brain temperature in the Mongolian gerbil during whole body hyperthermia]. AB - Somatosensory evoked potentials (SEP) have been applied to many men and several animals with cerebral ischemia. But in the Mongolian gerbil, one of the most common models of cerebral infarction, the wave form and the latency of SEP have been studied by few authors. In this report, we studied the effects of hyperthermia on SEP in the gerbil. Six gerbils weighting 40 to 50g were anesthetized and heated with ultra-red ray. Brain and rectal temperatures were continuously monitored. The brain temperature changed from 35 degrees C to 42 degrees C during heating, then returned to 37 degrees C with cooling. Typical SEP peaks have been labelled according to their positive or negative character and their sequential latency determination. The latency of the major positive voltage deflection, P1, was 9.97 +/- 9.94 ms at 37 degrees C. The negative deflection before P1 has been labelled as N0 and the negative waves after P1 and N1 and N2. Peak latency of SEP was significantly reduced gradually during hyperthermia, and increased gradually with recooling. The correlation between the latency of SEP and the brain temperature was very close. Our results emphasize the importance of measurement of SEP during hyperthermia as a monitor of the brain temperature and during experiment for maintenance of the body temperature at 37 degrees C. PMID- 1910946 TI - [Effects of hypothermal and circulatory arrest on the auditory brainstem response during operation in children]. AB - Twenty-two children were monitored by the auditory brainstem response (ABR) during the open chest and/or open heart surgery for cardiac anomalies under the extracorporeal circulation (ECC) with moderate to deep hypothermia. These patients were divided into two groups, namely, the ECC only group (group A: 9 cases) and the total circulatory arrest (TCA) group (group B: 13 cases). The mean age of group A was 36 months and group B was 6.1 months. In group A, moderate hypothermia was conducted with the rectal temperature ranging from 25 degrees C to 30 degrees C, and in group B profound hypothermia was conducted lowering the temperature to 18 degrees C. The ABR recorded at the following points, namely; before inducing anesthesia, before lowering the body temperatures, during the cooling process, at the time of TCA, and during the rewarming process. Accompanying the decrease in body temperature the peak latency of waves I, III and V were markedly prolonged. When the rectal temperature fell to 23 degrees C, the peak latency of each wave was prolonged to about 150% of their precooling values at 36 degrees C. When it fell to 22 degrees C, the ABR disappeared entirely in 16 of 22 cases, and in remaining 6 cases, only I wave was detected. During rewarming, in both the A and B groups, at 24 degrees C, the wave of ABR started to reappear beginning with I waves, and on reaching 26 degrees C, I, III and V waves from became detectable. The peak latency of all waves at rectal temperature of 33 degrees C recovered to almost the same values as these at 36 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1910947 TI - [The studies of melatonin values in the cerebrospinal fluid of hydrocephalic patients]. AB - The changes in daytime levels of melatonin (MLT) in the cerebrospinal fluid (CSF) of twenty seven hydrocephalic patients were studied by the high-performance liquid chromatography (HPLC) method. Patients comprised three with congenital hydrocephalus (spina bifida 1, Chiari type II malformation 2), four post meningitic hydrocephalus, fifteen brain tumors (chiasmal germinoma 3; malignant glioma of frontal 3, and temporal lobes 1; germinoma 1, teratoma 2, yolk sac tumor 1, epidermoid 1 in pineal region) and five cases of normal pressure hydrocephalus. CSF was collected between 0930 and 1030 h through puncture of the flushing device of shunt system or the lateral ventricle. The lowest value of MLT detected by HPLC was 15 pg/ml. Melatonin values were higher in patients aged under 10 years than over 20 years in the absence of meningitis or tumor in the pineal region. Even at ages over 15 years, higher CSF MLT values were obtained in the patients with meningitis or tumors in the pineal region. These results suggest that the inflammation or invasion of tumor into the pineal gland may stimulate the secretion of MLT by the pineal gland. However, lower MLT values were obtained in all patients over 40 years old. For these reasons, if one may use the changes of MLT values in CSF as a tumor marker or for determination of the treatment modality, time of CSF collection, age of patient, location or character of the tumor and presence of meningitis should be given due consideration. Also, the presence or absence of the rhythmical changes of melatonin values in a day following circadian rhythm are very important in determination of the treatment modality. PMID- 1910948 TI - [Effect of calcium channel antagonist (nicardipine) on growth hormone and prolactin secretion in pituitary adenomas]. AB - This study was designed to investigate the effect of calcium channel antagonist (nicardipine) on basal and bromocriptine-inhibited GH or PRL secretion in eight patients with pituitary adenomas (six GH producing adenomas and two prolactinomas). GH or PRL was measured in blood collected at intervals for 12 hours after oral administration of nicardipine (Nc) (40 mg) and/or bromocriptine (Br) (2.5 mg) in each case. In vitro, pituitary adenoma cells were incubated in media containing Nc (200 ng/ml) and/or Br (200 ng/ml) over a 72-h period, and then in drugs-free media for three days. Media were collected at 24-h intervals and assayed for GH or PRL. In three of six GH producing pituitary adenomas, GH secretion was inhibited by Nc both in vivo and in vitro. In prolactinomas, PRL secretion was inhibited by Nc in vitro, but in vivo, an increase of plasma PRL levels was observed after Nc administration in one of two cases. In two acromegalic patients and one patient with prolactinoma, Nc reduced the suppression of GH or PRL secretion induced by Br. These findings indicate that influx of extracellular calcium plays an important part in both GH and PRL secretion in functioning pituitary adenomas, and that Nc effects on GH and PRL secretion in pituitary adenomas by blocking of influx of calcium and/or antidopaminergic action. It is considered that the combined administration of calcium channel antagonist (Nc) and Br for acromegalic patients and administration of Nc for patients with prolactinomas should be avoided. PMID- 1910949 TI - [Quantification of wallerian degeneration of the pyramidal tract in the capsular region by magnetic resonance imaging]. AB - Using magnetic resonance imaging, we studied 23 patients with motor deficit associated with cerebrovascular disease of the internal capsule. According to the severity of the motor deficits, 23 patients were divided into three groups (severe group...9, moderately severe group...8, mild group...6). A coronal T2 weighted image was obtained along a straight line between the front edge of the medulla and the deepest point of the interpeduncular cistern in a midsagittal T1 weighted image. It was revealed that wallerian degeneration extended continuously from part of the internal capsule down to the pons or medulla or the decussation in all patients. The area of wallerian degeneration in the pons and the area of half the pons were calculated from the coronal T2-weighted image. Moreover, the wallerian index was calculated as: (area of wallerian degeneration in pons divided by area of half the pons) X 100. Values of the wallerian index +/- SD were 26.4 +/- 5.1 in the severe group, 19.2 +/- 5.6 in the moderately severe group, and 10.0 +/- 5.4 in the mild group. There were significant differences among the three groups. We concluded that the area of wallerian degeneration was related to the severity of motor deficits. PMID- 1910950 TI - [Selective enhancement of tumor blood flow and drug delivery to brain tumors in experimental rat gliomas under angiotensin II-induced hypertension]. AB - Regional blood flow of brain tumors and normal brain tissue of rats before and during angiotensin II (AT II)-induced hypertension were measured using an electrolytic flowmeter and a laser flowmeter. Etoposide concentration in the tumor and brain tissue after intracarotid administration were also measured in brain tumor bearing rats with or without AT II-induced hypertension. A suspension of 5 x 10(5)/10 microliters 9L gliosarcoma cells was inoculated into the left caudate-putamen of CD Fischer 344 rats. Before induced hypertension, regional blood flow of the tumor (28.2 +/- 2.6 ml/100 g/min; mean +/- SEM) and the contralateral caudate-putamen (23.0 +/- 1.8 ml/100g/min) in the tumor bearing rats were significantly lower than that of the caudate-putamen (43.9 +/- 4.1 ml/100g/min) in the normal rats (p less than 0.01). Intravenous administration of AT II at a dose of 0.4-0.6 microgram/body/min increased the mean arterial blood pressure from 96.5 +/- 4.7 mmHg to 138.0 +/- 3.6 mmHg. AT II-induced hypertension resulted in an approximate 1.8(1.1 - 3.6)-fold increase in the regional tumor blood flow. On the other hand the regional blood flow of the contralateral caudate-putamen was slightly decreased at the rate of 6%. The mean concentration of etoposide with AT II-induced hypertension in the tumor tissue was 2.2-fold higher than that without AT II-induced hypertension. However, etoposide delivery to normal brain tissue was small. From these results, induced hypertension with intravenously administrated AT II selectively increase the tumor blood flow and drug delivery to brain tumor tissue. Intracarotid chemotherapy with AT II-induced hypertension might contribute to enhance therapeutic effect of malignant brain tumors. PMID- 1910951 TI - [Three-dimensional MR brain image using volume rendering method]. AB - 3-dimensional image reconstructed from the data of computer tomography has provided useful informations for the pre-operative evaluation in the field of neurosurgery and plastic surgery. However CT has failed to visualized the 3 dimensional surface image of the central nervous system. On the other hand the progress of high-speed data acquisition technique and 3-dimensional fourier transformation has enabled the practical 3-dimensional image using magnetic resonance imager. However for the visualization of a pure surface image of the brain and spinal cord a sophisticated method and special image work station has been necessary. The authors describe a technique for the pure surface image of the brain and spinal cord using a normal mini-computer system and magnetic resonance imager. This image has a good correlation to the macroscopic anatomical brain surface (sulci and gyri). PMID- 1910952 TI - [Study of 123I-IMP SPECT on diabetic patients]. AB - The involvement of peripheral nerves and nerve roots often leads to neurological manifestations which have frequently been described in association with diabetes mellitus. Whether there is any specific involvement of the central nervous system in this process has yet to be determined. Recently, many reports have suggested that significant neurophysiologic abnormalities in the central nervous system can sometimes be found in diabetic patients. In order to accurately examine the existence of central nervous system involvement in patients with diabetes mellitus, comparisons of 123I-IMP (IMP) washout rates were made between normal adults (n = 19, average age 43.3 years) and diabetic patients (n = 23, average age 43.3 years), and these results were graphically demonstrated by color images. Early images were obtained 30 minutes after intravenous injection, while delayed images were made 4 hours after injection. The IMP washout rate was obtained by subtracting the values of the delayed image with the early image. The standard deviation (SD) of the IMP washout rate for each patient was compared to the averaged SD obtained from healthy adults. After calculating the deviation from SD levels of healthy adults, we made an image of the patient's IMP washout rates. These images were divided into seven degrees (I, II: normal, III, IV: borderline, V-VII: abnormal) and the ratio of each degree was expressed by a histogram in each cerebral hemisphere as the washout rate index. In 23 diabetic subjects, seven patients were found to be borderline while sixteen patients were abnormal. These impairments were not related either to the presence of diabetic neuropathies or the duration of disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1910953 TI - [The application of in vivo diffusion weighted magnetic resonance imaging to intracranial disorders]. AB - We have developed a magnetic resonance (MR) spin echo method to obtain diffusion weighted imaging using motion-probing gradient (MPG) pulses in one or three orthogonal directions before and after a 180 degree pulse. Phantom models containing water and acetone, normal volunteers and patients with brain tumors, brain edema and infarction were examined. Experimental models of brain edema including triethyltin intoxication and cold injuries were also examined in Wistar rats. MRI was performed at a 1.0-T clinical machine or a 4.7-T experimental machine using spin echo pulse sequences with or without additional MPGs on one or three orthogonal axes. The one direction method was useful to define diffusion anisotropy of myelinated axonal fibers in white matter. Faster diffusion was detected in the white matter parallel to the direction of MPGs. On the other hand, slower diffusion was detected perpendicular to the direction of MPGs because the myelin sheath restricted water diffusion. The three orthogonal gradients method was useful to demonstrate the difference in the diffusion coefficients in various diseases due to its larger total gradient strength. The clear distinction between the cytotoxic edema, which revealed slower diffusion, and the vasogenic edema, which revealed faster diffusion, was demonstrated in the experimental models using diffusion weighted image. In the clinical cases, faster diffusion was demonstrated in the brain tumor and perifocal vasogenic edema, which was in agreement with the results in the experimental models of rats. Brain tumors such as low grade astrocytoma with microcysts and perifocal vasogenic edema have very wide extracellular space.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1910955 TI - Serum osteocalcin (bone Gla-protein), an index of bone growth in lambs. Comparison with age-related histomorphometric changes. AB - In 96 normal male sheep, we studied the variations with age of serum osteocalcin (bone Gla-protein), measured with an assay specific for ovine osteocalcin. We compared serum osteocalcin with the main histomorphometric parameters of bone growth measured on the metacarpus of 20 normal lambs from birth to 90 days of age. Serum osteocalcin significantly decreased with age (r = -0.70, p less than 0.001), particularly during the first 90 days of life (r = -0.85, p less than 0.001). During this growth period, serum osteocalcin was significantly correlated with the appositional rate (r = +0.73, p less than 0.001), the rate of longitudinal bone growth (r = +0.68, p less than 0.002), the rate of production of chondrocytes in the growth plate (r = +0.60, p less than 0.007), and the thickness of the growth plate (r = +0.79, p less than 0.001). In low birth weight male lambs (growth-retarded animals), serum osteocalcin was significantly lower at birth when compared to normal lambs (271 +/- 156 vs. 535 +/- 169 micrograms/l, p less than 0.001), and was also significantly correlated with histomorphometric parameters. We conclude that serum osteocalcin, which is already known as a sensitive and specific marker of bone formation, is also a sensitive biochemical marker of skeletal growth in normal and growth-retarded lambs. In addition, sheep appears as a valid animal for experimental studies on bone growth. PMID- 1910954 TI - Effects of Carbetimer, a new antineoplastic drug, on bone metabolism. AB - Carbetimer is a new antineoplastic agent whose main side effects consist of neurotoxicity and long-term dose-dependent hypercalcemia. We previously showed that Carbetimer is a potent calcium chelator responsible for an acute decrease in ionized Ca levels observed in vivo. However, the mechanism of the progressive increase in serum Ca remains unknown. We have evaluated the bone-resorbing effects of Carbetimer on 45Ca-prelabelled neonatal mouse calvariae. Carbetimer induced a dose-dependent increase in 45Ca release which started at a concentration of 1 mg/ml and reached a mean of 3.3 times the control values at 10 mg/ml. This marked increase in 45Ca release was similar on previously killed bones and could not be inhibited by calcitonin. Such concentrations are probably therapeutically relevant given the known affinity of Carbetimer for bone and the large daily doses administered to cancer patients (10-15 g). Since Carbetimer could exert its antineoplastic action through immunomodulation, we also studied its effects on the production of TNF-alpha and IFN-gamma which are also known to affect bone metabolism. Carbetimer did not stimulate TNF-alpha release from isolated normal human monocytes or lymphocytes, but it markedly inhibited T lymphocyte production of IFN-gamma, which became undetectable at a concentration of 1 mg of Carbetimer/ml. In summary, Carbetimer-induced hypercalcemia appears to be due to a direct stimulation of osteolysis, but possibly also to an inhibition of IFN-gamma production. PMID- 1910956 TI - The effect of growth hormone on fracture healing in old rats. AB - The healing of fractures is known to decrease with age. Several mechanisms have been identified that might explain this age-related decrease in capacity for fracture repair, one of them being a decrease in growth hormone secretion. In the present experiment, two-year-old male rats with a standardized tibial fracture were given biosynthetic human growth hormone (b-hGH, 2.7 mg/kg/day in two daily injections) during the first 40 days of fracture healing and the controls were injected with saline. After 40 or 80 days of healing, the mechanical properties of the healing fractures were evaluated by three-point bending. At day 40, no differences were found in mechanical properties of fractured and intact tibiae between b-hGH injected rats and saline injected controls. At day 80, ultimate load, stiffness, and ultimate stress of the fractures had increased by 78%, 63%, and 58%, respectively, compared with the controls. In the contralateral, intact tibiae, ultimate load and energy absorption had increased by 12% and 17%, respectively, compared with the controls. PMID- 1910957 TI - The effects of etidronate on trabecular bone remodeling in postmenopausal spinal osteoporosis: a randomized study comparing intermittent treatment and an ADFR regime. AB - Thirty-seven patients were randomized to receive intermittent cyclic etidronate (400 mg/day oral for 2 weeks, followed by 13 weeks off treatment) or an ADFR treatment (100 micrograms/day oral triiodothyronine for 7 days, followed by 400 mg/day etidronate for 2 weeks and 12 weeks off treatment). Supplemental calcium (120 mg/day) and vitamin D3 (400 IU/day) were given throughout the study period to all patients. Biochemical analyses, iliac-crest bone biopsies, and lumbar bone mineral content (BMC) measurements were performed before and during 60 weeks of treatment. Sixteen patients in the intermittent cyclic etidronate group and 15 in the ADFR group completed 60 weeks of treatment. Serum alkaline phosphatase decreased from 185 (43) (mean, (SD] to 144 (35) (p less than 0.001) and from 221 (69) to 156 (43) (p less than 0.002) during intermittent cyclic etidronate treatment and ADFR treatment, respectively, without any significant changes in renal hydroxyproline excretion. Final resorption depth, trabecular bone activation frequency, and bone formation rate decreased significantly from 51.5 (48.4/60.0) microns (median (25%/75% quartiles] to 44.0 (39.6/46.2) microns (p less than 0.04), from 0.30 (0.17/0.62) year-1 to 0.10 (0.02/0.19) year-1 (p less than 0.03) and from 0.035 (0.020/0.081) microns3/microns2/day to 0.015 (0.002/0.025) microns3/microns2/day, p less than 0.03 respectively, during intermittent cyclic etidronate treatment, but were unchanged during ADFR treatment. No significant changes in trabecular bone volume, bone balance per remodeling cycle, or BMC were noted in either treatment group; no evidence of osteomalacia was found. Intermittent cyclic etidronate treatment may be effective in preventing bone loss and in decreasing the risk of trabecular plate perforation, and thereby maintaining the integrity of bone architecture, in postmenopausal osteoporosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1910958 TI - Structural changes in aging bone: osteopenia in the proximal femurs of female mice. AB - A computerized image analysis system was used to quantitate age-related changes in the structure of the proximal femur in CW-1 female mice, ranging from 3 to 32 months of age. Morphological findings revealed a progressive thinning of bone trabeculae within the femoral head, accompanied by the development of marrow cavities in the cortical bone of the femoral neck and in the subchondral bone. As a result, the compact bone in senescent mice acquired an appearance similar to trabecular bone. Quantitative image analysis revealed a similarity in the pattern of changes in the three types of bone: cortical, trabecular, and subchondral. Bone density increased from 3 to 12 months of age and subsequently declined. A similar pattern was noted for the changes in the thickness of the cortical and the subchondral bone. Regression analysis revealed that the changes with age fitted a second-order model; thus it was possible to predict the age of maximal values for each parameter. Hence, the age of maximal bone density for cortical, trabecular, and subchondral bone was 12.3, 14.8, and 18.0 months, respectively. The rate of bone loss after 12 months was most prominent for trabecular bone (1.47% per month), so that by 32 months of age its overall mass had declined by 57% in comparison to peak values seen at 12 months of age (p less than 0.001). The density of the subchondral and cortical bones decreased at a slower rate (0.6% to 0.8% per month) and at the age of 32 months their values had decreased by 12% to 18% in comparison to those at 12 months (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1910959 TI - Partial loss of anabolic effect of prostaglandin E2 on bone after its withdrawal in rats. AB - The object of this study was to determine the fate of PGE2-induced new bone mass after withdrawal of PGE2 administration. Seven-month-old male Sprague-Dawley rats were given subcutaneous injections of 1, 3, and 6 mg PGE2/kg/d for 60 days and then withdrawn for 60 and 120 days. Histomorphometric analyses were performed on double fluorescent labeled undecalcified proximal tibial bone specimens. After 60 days of PGE2 treatment, a new steady state of increased trabecular bone area (+67% and +81% with 3 and 6 mg PGE2/kg/d) from woven bone and stimulated lamellar bone formation, elevated bone turnover, and shortened remodeling periods were achieved compared to age-matched controls. In contrast, after 60 and 120 days withdrawal of PGE2, a new steady state characterized by less trabecular bone area (+40% to +60% of controls with 3 and 6 mg/kg/d doses), normal lamellar bone formation, no woven bone formation from controls, and eroded surface greater than those seen in controls and previously in 60-day PGE2 treated rats. The decrease in new bone mass after withdrawal of PGE2 was due to a further elevation of bone resorption above that induced by the PGE2 treatment and a reduction in PGE2 stimulated bone formation activities. Although there is more trabecular bone than in controls after 120 days' withdrawal of PGE2, we postulate that the skeletal adaptation to mechanical usage will eventually reduce the bone mass to control levels. Thus, it is conservative to conclude that the anabolic effect of PGE2 was dependent upon continuous daily administration of PGE2 in these older rats. PMID- 1910960 TI - Microstructural changes of osteopenic trabeculae in the rat. AB - We studied the differences in the patterns of trabecular bone loss induced by various kinds of experimental osteopenia in the rat, including ovariectomy, sciatic neurotomy (partial paralysis of hind-limb), hemicordotomy (complete paralysis of hind-limb), and their combinations. The cut surface of the metaphysis of proximal tibiae from osteopenic and control rats was observed by scanning electron microscopy, and morphometric changes of the secondary spongiosa were determined by measurement of percent bone area, and number and width of trabeculae. Percent bone area decreased significantly compared with the Sham group in all operated groups except the sciatic neurotomy group, but the qualitative changes of trabeculae in osteopenia induced using different methods were definitely different. In the Sham-operated group of rats, conversion of rod trabeculae to plate trabeculae and thickening of trabeculae were observed over the course of the nine months following surgery. In the sciatic neurotomy group of rats, neither trabecular number nor width significantly changed at 12 weeks after surgery. In the ovariectomy group of rats at nine months after surgery, a significantly decreased trabecular number but unchanged trabecular width were observed, and disappearance of trabeculae was identified primarily in the central area. In the hemicordotomy group of rats at 12 weeks after surgery, significantly decreased trabecular width with unchanged trabecular number were observed and thinning of trabeculae was noted to be equal in the whole area of the proximal tibial secondary spongiosa. In rats subjected to sciatic neurotomy combined with ovariectomy, and in rats subjected to hemicordotomy combined with ovariectomy, both trabecular number and width were severely decreased in the whole area at 12 weeks after surgery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1910961 TI - Canine distemper virus localised in bone cells of patients with Paget's disease. AB - The technique of in situ hybridisation was applied using radioactively labelled riboprobes to examine for the presence of canine distemper (CDV) and measles (MV) RNA in Paget's disease of bone. The results indicate that in 41% of Paget's patients, CDV RNA could be detected in osteoclasts, osteoblasts, and osteocytes, but not in controls. In contrast, RNA to the measles virus was not detected. We suggest that CDV may in some cases play a role in the aetiology of Paget's disease. PMID- 1910962 TI - Homeostatic control of bone structure: an application of feedback theory. AB - The regulation of bone mass and structure in the weight-bearing skeleton is governed to a great extent by the mechanical demands placed upon the bone tissue. The apparent biological goal is the maintenance of a minimum adequate structure, in which the margin of safety between normal mechanical demands and fracture is balanced by the cost of excessive bone mass on mobility. Frost has developed two powerful postulates concerning bone adaptation: (a) there exist threshold levels of mechanical strain, above or below which bone adaptation is turned on, and (b) the set point for normal bone structure can be modulated by hormones. A model was developed, using Frost's postulates and simple feedback theory, that describes the interaction between biochemical influences and mechanical influences on bone structure. The model predicts that biochemical agents that influence bone structure independently of the mechanical feedback system (e.g., calcitonin) are capable of only limited anabolic effects on bone mass because their influences conflict with mechanical influences. However, biochemical agents that influence bone structure by changing the set point of the mechanical feedback system (e.g., estrogen) will provide lasting changes in bone structure. Age-related changes occur within the effector and transduction components of the mechanical feedback system that tend to make it sluggish. These changes may lead to increased bone fragility because the system is no longer capable of maintaining adequate bone structure. PMID- 1910964 TI - Sick dentists--an escalating problem. PMID- 1910963 TI - Biologically meaningful determinants of the in vitro strength of lumbar vertebrae. AB - Applying unbiased stereological methods and a new stereological parameter, star volume of cancellous bone, the bone structure of the first vertebral body was examined and compared with the compressive strength of the second lumbar vertebra. The material came from eight males, aged 33-69 years (mean 49 years) and seven women, aged 22-87 years (mean 52 years) without malignant or metabolic bone disease. From these individuals, first and second lumbar vertebral body were obtained at autopsy. The heights and weights of the individuals were recorded. The following structural parameters were estimated on undecalcified, seven microns, Goldner-Trichrome stained vertical sections: fractional volume of trabecular bone (BV/TV%), mean trabecular thickness (Tb.Th.l1 microns), trabecular star volume (V*tr mm3), marrow space star volume (V* m.space mm3), and mean thickness of the lateral cortical ring (microns). The compressive strength of whole vertebral body, mean cross sectional area (cm2), and ash density (g/cm3) were estimated and the data were compared to bone histomorphometric estimates. A significant decrease with age for all parameters was found except for marrow space star volume, which increased. With compressive strength as the dependent variable and all other parameters as independent variables, it was shown by standard multiple regression analysis that the in vitro tested compressive strength could be predicted from mean cortical thickness, mean cross sectional area, and marrow space star volume or ash density with a multiple, squared coefficient of regression (r2) of 0.95 when the height and sex of the individual were known.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1910965 TI - 'AIDS--a two-way risk'. PMID- 1910966 TI - Cross infection: controlling the directives. PMID- 1910967 TI - 'Why free sugars consumption should be below 15 kg per person per year in industrialised countries: the dental evidence'. PMID- 1910968 TI - 'Reducing the discomfort of injections'. PMID- 1910969 TI - Effectiveness of pre-brushing rinses in oral hygiene. PMID- 1910970 TI - The frequency of dental attendance of Scottish dentate adults between 1978 and 1988. AB - The dental attendance of a sample of dentate adults (n = 702) within the National Health Service in Scotland was monitored longitudinally between 1978 and 1988. The attendance pattern of the sample appeared to be no different between 1983-88 than in the preceding 5 years, which suggests that the attendance behaviour of the sample has not changed significantly. National figures, available for the same period, show an increase in the number of courses of dental treatment provided. These figures were examined in detail, and the analysis suggested that only 40% of the increase in number of courses provided in 1988 compared with 1978 could be accounted for by an improvement in attendance patterns among Scottish adults as a whole. The remaining 60% could be attributed to a greater requirement for dental care to cater for the increased proportion of the Scottish population who retained their own teeth in 1988. Only 16% of the sample consistently attended for dental care within 2 years of a previous dental course (which is the criterion for remaining under continuing care in the new General Dental Service contract). PMID- 1910971 TI - The significance of maintaining the stability of the natural microflora of the mouth. AB - The mouth, like other areas of the digestive tract, possesses a natural microflora, the presence of which confers several beneficial properties to the host. However, in the absence of adequate oral hygiene, dental plaque can accumulate beyond levels compatible with oral health. This leads to shifts in the balance of the predominant bacteria away from those associated with health; such shifts can predispose a site to caries or periodontal diseases. Treatment should be designed, therefore, to control rather than to eliminate dental plaque. Possible strategies to maintain the stability and beneficial properties of the natural oral microflora include the stimulation of saliva flow for an extended period directly after a meal, the avoidance of fermentable carbohydrates during between-meal periods, and improvements to oral hygiene, for example, by using products containing antiplaque or antimicrobial agents. PMID- 1910972 TI - Clinical audit and self-assessment initiatives. PMID- 1910973 TI - 'The health of nation'. PMID- 1910974 TI - 'Leadership in dentistry'. PMID- 1910975 TI - 'A clinical trial to evaluate plaque removal with a double-headed toothbrush'. PMID- 1910976 TI - 'A denture of a lifetime'. PMID- 1910977 TI - 'Domestic water treatment appliances and the fluoride ion'. PMID- 1910979 TI - 'Student apoplexy--irrelevance of BDJ'. PMID- 1910978 TI - Childhood tobacco smoking. PMID- 1910980 TI - 'A 10-year comparison of general dental service care in the northern region'. PMID- 1910981 TI - An assessment of dental anxiety in children. AB - The aims of this study were to assess child behaviour in a dental surgery and to isolate the variables most closely associated with lack of cooperation by means of a questionnaire/interview. Sixty-five children aged 6-18 years, who had been referred to one dentist because of poor cooperation, formed the study group. Forty-two children of similar age, treated by the same dentist, but referred for reasons other than lack of cooperation, acted as the control. Assessments of anxiety were made independently by a psychologist who used a number of indices, including the Child Manifest Anxiety Scale (CMAS), Melamed's Child Behaviour Rating Scale and the Venham Picture Scale. Fifty-one children in the study group had experienced a general anaesthetic for dental treatment compared with five in the control group (P less than 0.001). Parents of children in the study group could identify specific instances which contributed to fear of dentistry in 75% of cases. The CMAS found no difference between the groups in general anxiety, but anxiety and cooperation ratings made by parent and dentist in the dental surgery showed significant differences between the two groups, as did the results of the Venham Picture Scale. PMID- 1910982 TI - Oxygen saturation during third molar removal with local anaesthetic alone and in combination with intravenous sedation. AB - Oxygen saturation was recorded in 96 adults undergoing removal of third molar teeth in the dental surgery. Half the patients received local anaesthetic alone; the remainder received, in addition, intravenous midazolam. Patients receiving sedation sustained the greatest falls in oxygen saturation. However, in 10 out of 48 patients undergoing third molar removal with LA alone, oxygen saturations in the range of 93-89% were recorded. The results of this study suggest that all patients undergoing removal of third molars are at risk of hypoxia. Short episodes of hypoxia may be of little consequence in healthy patients, but in compromised patients early detection may avoid serious complications. PMID- 1910983 TI - Odontogenic myxoma: an orthodontic presentation. AB - A maxillary odontogenic myxoma in a 17-year-old male was diagnosed as a result of his presenting to an orthodontist. Histological diagnosis was obtained following enucleation, and a further wide local excision performed as definitive treatment. The origin of the tumour was most likely from the follicular remnants of a previously exposed canine tooth. PMID- 1910984 TI - The Menzies Campbell Lecture. The fair face of dentistry--from anathema to acceptance. AB - 'What is history?' was the challenge issued by Gibbon, the great historian of the Roman Empire. 'Little more', he observed, 'than a register of the crimes, follies and misfortunes of men'. In this lecture I will attempt to redress this inequality and demonstrate that the 'crimes, follies and misfortunes' of women also have a place in history and, at the same time, uncover the 'fair face of dentistry'. I intend to paint a wide canvas, and to relate events and achievements to the sociological changes of contemporary society. PMID- 1910985 TI - Percutaneous embolization of ruptured splanchnic artery pseudoaneurysms. AB - The usefulness of emergent embolotherapy was evaluated in 17 patients with life threatening hemorrhage from 18 ruptured splanchnic artery pseudoaneurysms. Complete hemostasis was obtained in 16 out of 17 patients by embolotherapy. Of the 12 initial embolization procedures with permanent embolic materials including stainless steel coils, microcoils, and Ivalon, complete cessation of bleeding was obtained in 11. On the other hand, 6 out of 9 initial embolization procedures with Gelfoam particles failed to halt bleeding, and additional embolization with permanent embolic materials was required. Emergent embolization with permanent embolic materials using superselective catheterization should be considered the initial treatment of choice for ruptured splanchnic artery pseudoaneurysms. PMID- 1910986 TI - Peritoneal mesothelioma. Radiologic appearances correlated with histology. AB - Previous imaging reports of peritoneal mesothelioma have described a variety of radiologic appearances, but have not included its pathologic classification. We retrospectively reviewed 10 cases of peritoneal mesothelioma representing the following histologic categories: 7 epithelial, 2 sarcomatoid, and one biphasic. By imaging, epithelial mesotheliomas demonstrated diffuse thickening of the peritoneum and mesentery and/or multiple small nodules. The sarcomatoid-type appeared as a mass and the biphasic-type had radiologic and gross pathologic features of both sarcomatoid and epithelial types. We conclude that peritoneal mesothelioma presents with a wide spectrum of radiographic appearances and should therefore be included in the differential diagnoses of diffuse as well as localized peritoneal processes. PMID- 1910988 TI - Radiologic findings in renal oncocytoma. AB - The imaging findings of 36 renal oncocytomas in 32 patients were evaluated retrospectively. Twenty-two patients underwent ultrasound (US), 16 CT, 25 angiography, 19 urography, and 6 fine-needle biopsy. At US 8 of the oncocytomas were isoechoic, 7 hyperechoic, and 7 hypoechoic. The structure was homogeneous in 59% and nonhomogeneous in 41%. At plain CT 12 oncocytomas were homogeneously hypodense, 3 isodense, and one hyperdense. Contrast enhancement was homogeneous in 10 and inhomogeneous in 4 cases. A stellate scar was detected in one case, and in one case a contrast study was not performed. At angiography the oncocytomas were hypervascular in 21, hypovascular in 3 cases, and one was not detected. Nineteen of the tumors were well delineated. A spokewheel arterial pattern was detected in 3 tumors. The cytologic diagnosis was benign renal oncocytoma in 4 cases and highly suggestive of oncocytoma in 2 cases. We conclude that the homogeneity of a renal tumor at US and at CT may suggest the possibility of oncocytoma. US-guided fine-needle biopsy is a useful diagnostic tool in patients who need a precise presurgical diagnosis. PMID- 1910987 TI - Scintigraphy with 99mTc-HMPAO labeled leukocytes in acute cholecystitis. AB - 99mTc-HMPAO labeled leukocyte scanning was performed on 38 patients with clinically suspected acute cholecystitis (AC) to evaluate its diagnostic value. The typical finding was an increasing accumulation of the tracer in the gallbladder wall in a 4 hour series of scintigrams. Leukocyte scan was positive in 16 of 17 patients with surgically and histologically confirmed AC. There were no false-positive findings. The sensitivity, specificity, and accuracy of scintigraphy were 94, 100, and 96%, respectively. In 2 patients with acute acalculous cholecystitis true-positive findings were observed. Scintigraphy with 99mTc-HMPAO labeled leukocytes is a valuable new imaging method in AC. PMID- 1910989 TI - Influence of renal angiography in living potential kidney donors. AB - The angiograms of 258 potential kidney donors were retrospectively reviewed to assess the influence of angiography for deciding whether or not to accept the potential donor for nephrectomy and which kidney to use for transplantation. Twenty-five potential donors were rejected. In only 8 of these was angiography necessary to reveal the pathology. Angiography was found to be important in deciding which kidney to donate. In 81 donors the right kidney was used for donation and in 50 this decision was based on findings at angiography. PMID- 1910990 TI - Accuracy of adrenal biopsy guided by ultrasound and CT. AB - We reviewed the results of fine needle biopsy of the adrenal glands guided by ultrasonography or CT in 56 patients. The final diagnoses, obtained at operation, autopsy or follow-up were: metastasis (n = 22), adenoma (n = 21), adrenal cyst (n = 6), hematoma (n = 3), lymphoma (n = 1), pheochromocytoma (n = 1), lymph node (n = 1), and amyloid mass (n = 1). Sufficient cytologic material was obtained in 96.4% (54/56). The overall accuracy to differentiate benign from malignant disease was 85.7% (48/56), 2 were false-negative, one was false-positive. The biopsy was inconclusive ("possibly malignant") in 3 patients, 2 of whom had an additional cutting needle biopsy yielding a correct positive finding. No complications occurred. We conclude that in disseminated malignant disease with suspected adrenal metastases diagnostic results can be obtained with guided fine needle biopsy. Biopsy in primary adrenal lesions is helpful, especially if the aspirate of the lesion turns out to be composed of something other than adrenal cells. PMID- 1910993 TI - Traumatic trabecular lesions observed on MR imaging of the knee. AB - Examinations carried out on 302 consecutive patients with MR of the knee between January 1988 and March 1989 were reviewed for detection of trabecular lesion. Twenty-seven patients found presenting trabecular lesion were further reviewed with specific reference to their activity level and need for specific therapy to determine the clinical significance of the trabecular lesion. Twenty-one of the trabecular lesions were in the femur, 5 were in the tibia, and one was in the fibula. Three of them were associated with a direct trauma, 12 with a valgus type injury, 3 with pure rotation mechanism, and 5 with a combination of valgus and rotation. In 17 cases trabecular lesion was a single finding, in 10 cases it was associated with some ligamentous tear. At the follow-up visit, 26 of the 27 patients with trabecular lesion had no symptoms, and the patient with moderate knee symptoms had had similar knee symptoms prior to the accident due to an osteochondral defect. We conclude that a trabecular lesion in an MR image is a benign bone change associated with knee trauma which heals without sequelae. PMID- 1910992 TI - Aortography delays surgery of CT proven acute traumatic rupture of the thoracic aorta. Case report. AB - A case of acute traumatic rupture of the thoracic aorta was diagnosed by dynamic CT. Angiographic conformation was required, delaying surgical repair and contributing to the fatal outcome. If reliable findings of acute traumatic rupture of the thoracic aorta are shown by CT, we question the usefulness of angiographic confirmation in such cases. PMID- 1910991 TI - Radioimmunoscintigraphy of gynecologic tumors with 131I-labeled anti-PLAP monoclonal antibodies. AB - Radioimmunoscintigraphy (RIS) was performed in 20 patients with gynecologic tumors, 14 ovarian, 5 cervical, and one endometrial carcinoma. One murine monoclonal antibody (mab) against placental alkaline phosphatase (H7) was used after radiolabeling with 131I. The labeling procedure yielded antibodies with specific activity varying between 60 and 73 MBq/mg mab. Each patient received 57 to 100 MBq of the preparation. RIS was performed 7 to 35 days later. Patients with ovarian adenocarcinoma had an accumulation of activity on RIS at tumor sites (79%, 11/14) verified by ultrasonography, CT, and clinical examination. A low or absent accumulation of activity was seen in patients with cervical tumors. The patient with an endometrial adenocarcinoma was seen to have an activity accumulation at RIS corresponding to tumor sites determined by ultrasound and/or CT. It is concluded that RIS using monoclonal antibodies against placental alkaline phosphatase can provide information which will supplement that gained from other investigations of patients with ovarian adenocarcinomas. PMID- 1910994 TI - High-resolution real-time sonography and MR imaging in assessment of osteocartilaginous exostoses. AB - High-resolution real-time ultrasonography (US) and MR imaging, using both spin echo (SE) and gradient-echo (GE) sequences, were performed prospectively in 14 patients with solitary osteocartilaginous exostoses to assess cartilage cap thickness and bursa formation. Results were compared to surgical and histopathologic findings in all cases. Both US and MR imaging were useful in evaluating exostotic cartilage cap thickness, which is supposed to be the most reliable sign of malignant transformation. Hyaline cartilage matrix had distinctive features in US and MR imaging caused by its specific histologic composition. The formation of bursae over the protruding exostoses, which results in pain and clinically could raise the suspicion of growth and malignant transformation, was demonstrated best using GE sequences. MR imaging was thus superior to US in the detection of bursa formation. PMID- 1910995 TI - Mammographic follow-up after breast conserving surgery and postoperative radiotherapy without boost irradiation for mammary carcinoma. AB - Pre- and postoperative mammograms were reviewed in 103 women undergoing conservation surgery and irradiation for breast cancer stage I. The main reactions to radiotherapy were increased breast parenchymal density and increased skin thickness. Changes reached a peak at 9 months. No new changes were seen at 2 years, and most had regressed at this time. Following surgery, 71 of the patients displayed noticeable scar tissue in the surgical area, sometimes causing diagnostic difficulties. Two of the patients had a local recurrence of carcinoma, while 3 developed cancer in the other breast. PMID- 1910996 TI - Preoperative localization of enlarged parathyroid glands with ultrasonically guided fine needle aspiration for parathyroid hormone assay. AB - For preoperative localization of enlarged parathyroid glands, several imaging techniques have been used. In this study we demonstrate the feasibility of using ultrasonography with fine needle aspiration for parathyroid hormone assay as a preoperative localization procedure in 21 patients with primary hyperparathyroidism. A single adenoma was found in 18 patients while 3 patients had multiglandular disease. Ultrasonically guided fine needle biopsy was possible in 11 cases. In 8 of these aspirates, a high parathyroid hormone content was found. In all 8 cases the localization was confirmed at surgery. We conclude that the efficiency to preoperatively localize enlarged parathyroid glands is enhanced by fine needle aspiration. PMID- 1910997 TI - Salivary SPECT and factor analysis in Sjogren's syndrome. AB - Salivary SPECT and factor analysis in Sjogren's syndrome were performed in 17 patients and 6 volunteers as controls. The ability of SPECT to detect small differences in the level of uptake can be used to separate glands from background even when uptake is reduced as in the patients with Sjogren's syndrome. In control and probable Sjogren's syndrome groups the uptake ratio of the submandibular gland to parotid gland on salivary SPECT (S/P ratio) was less than 1.0. However, in the definite Sjogren's syndrome group, the ratio was more than 1.0. Moreover, the ratio in all patients with sialectasia, which is characteristic of Sjogren's syndrome, was more than 1.0. Salivary factor analysis of normal parotid glands showed slowly increasing patterns of uptake and normal submandibular glands had rapidly increasing patterns of uptake. However, in the definite Sjogren's syndrome group, the factor analysis patterns were altered, with slowly increasing patterns dominating both in the parotid and submandibular glands. These results suggest that the S/P ratio in salivary SPECT and salivary factor analysis provide additional radiologic criteria in diagnosing Sjogren's syndrome. PMID- 1910998 TI - Central nervous system reactions to cervical myelography. AB - In a double blind prospective study of side effects to cervical myelography 38 patients were evaluated with neurologic examination, electroencephalography (EEG), brainstem evoked response (BER), somatosensory evoked responses (SSER), and continuous reaction times prior to and at 6 h and 24 h after myelography with either metrizamide or iohexol. A difference in the incidence of side effects (for example headache, dizziness, nausea, and neck pain) to the two different contrast media indicated that the inconveniences related to myelography were not only due to the spinal puncture. A contrast medium effect on the central nervous system varying from one agent to another was present. A high frequency of EEG deteriorations among patients with adverse clinical reactions and on only discrete affection upon BER indicated the reaction to be located to the cerebral cortex. Weakened tendon reflexes and reduced strength in the upper extremities were probably caused by blockade in the motor roots as SSER were normal indicating no affection of the sensory pathways. This hypothesis is in agreement with the fact that the patients were in the prone position in the first phase of the investigation causing the highest concentration of contrast medium around the motor roots and the anterior part of the spinal cord. Difference in metabolic effect may explain differences in side effects of metrizamide and iohexol. PMID- 1910999 TI - Powdered diatrizoic acid for radiography of the respiratory tract. Part I. Experimental investigation. AB - Powdered diatrizoic acid as a contrast medium administered by inhalation and insufflation for visualization of the airways was tested in vitro and in 21 dogs. Good radiopacity of the contrast medium and its antibacterial activity was found in vitro. In the majority of animal experiments visualization of the bronchial tree down to segmental and partially to subsegmental bronchi with only minimal agglomeration of contrast medium and with good or very good demonstration of anatomic details was achieved. In the majority of dogs contrast medium was eliminated from the lungs within 18 hours. Arterial blood gases tested on 5 dogs showed only unimportant changes after contrast medium administration. No adverse reactions were observed. Histologic and ultrastructural examinations after contrast studies showed phagocytic reaction to diatrizoic acid, transient impairment of production of surfactant, reactive changes of bronchial mucosa, and no fibrotic changes in the long-term observation. PMID- 1911000 TI - Digital image processing to remove blur from linear tomography of the lung. AB - We have studied digital image processing methods to reduce blur in linear tomography of the lung performed with the Fuji computed radiography (FCR) system. One-dimensional unsharp (blur) mask filtering in the direction of tomographic movement was found to be effective in reducing blur. The appearance of the processed tomograms varied depending largely on the properties of the unsharp mask filters applied. With regard to the spatial frequency response of the filter, a high mid-frequency response and a low low-frequency response of the tomographic image data was most effective in obtaining high image quality tomograms. When the standard 2-dimensional unsharp mask technique of the FCR system was additionally applied to the one-dimensional unsharp mask processed tomogram, the clarity of the tomogram was further enhanced. These observations may also be helpful when considering image processing to obtain diagnostically informative digital radiography. PMID- 1911001 TI - Nickel-doped agarose gel phantoms in MR imaging. AB - A method for the production of a tissue-mimicking phantom material for MR imaging is described. The material consists of a nickel-doped agarose gel. The T1 and T2 values of the gel can be varied independently by changing the relative amounts of nickel and agarose. Practically any T1 and T2 combination of clinical interest can be obtained. The long-term stability was studied and found to be good. The relaxation times were estimated using an MR analyzer. The accuracy and the reproducibility of these measurements were evaluated and found to be reassuring. Gel phantoms were also scanned in an MR unit. The signal strength of an inversion recovery sequence was evaluated using the gel phantoms in order to verify their usefulness. These measurements were compared to theory with good agreement. Furthermore, tissue-equivalent phantoms were made. Gels resembling gray matter, white matter, and CSF were scanned. Comparisons with clinical in vivo scans, as well as calculated levels were made. It is anticipated that the gel phantoms described here will be useful in quality assurance as well as in pulse sequence optimization. PMID- 1911002 TI - Three-dimensional imaging of the liver. PMID- 1911003 TI - Evaluation of a restricted-volume technique for T1 measurements in the vicinity of object interfaces. PMID- 1911004 TI - Gender influences upon the executive role. PMID- 1911005 TI - From shared governance in nursing to integrated patient care teams. PMID- 1911006 TI - Decentralizing education facilitates academic pursuits for nurses. PMID- 1911007 TI - Pain after surgery. PMID- 1911008 TI - Double-blind comparison of the morphine sparing effect of continuous and intermittent i.m. administration of ketorolac. AB - The morphine sparing effect of ketorolac 10 mg administered 4-hourly by intermittent i.m. injection was compared with a continuous i.m. infusion in a double-blind, placebo-controlled trial in patients undergoing upper abdominal surgery. During the 48-h postoperative period, each patient was provided with a patient-controlled analgesia (PCA) system which delivered bolus doses of morphine and administered the intermittent i.m. doses automatically via a computer controlled pump. In the first 24 h after surgery, there was a significant reduction in morphine demanded by both groups receiving ketorolac compared with placebo. Patients who received a continuous infusion of ketorolac after abdominal surgery required a median dose of morphine by PCA which was 49% less than controls. In the second 24 h and over the entire 48 h of the study, patients in the continuous group required significantly less morphine than those in the placebo group. The intermittent group used less than the placebo group, but this was not significant. PMID- 1911010 TI - Cardiovascular effects and regional clearances of i.v. bupivacaine in sheep: enantiomeric analysis. AB - All currently available aminoacylaniline local anaesthetics, except lignocaine, contain a chiral centre but are used as racemates, a fact usually ignored in pharmacokinetic studies. This study reports the cardiovascular effects, and the regional and total body clearances of the enantiomers of bupivacaine determined at two steady state periods (3-4 h and 23-24 h) during continuous i.v. infusion to subtoxic concentrations in conscious sheep. Racemic (RS)-bupivacaine hydrochloride 1 mg min-1, was infused in five sheep that had been prepared at least 1 week previously with appropriate intravascular cannulae. The infusion of RS-bupivacaine produced constant arterial R(+)- and s(-)-bupivacaine concentrations of 0.20-0.68 mg litre-1 and 0.22-0.94 mg litre-1, respectively. This caused no appreciable cardiovascular effects. The hepatic clearance of R(+)- was greater than that of S(-)-bupivacaine (P less than 0.05) with mean (SD) clearance at the two respective time periods being 1.37 (0.78) and 1.47 (0.57) litre min-1 and 1.01 (0.72) and 1.29 (0.47) litre min-1. There was no significant clearance of either enantiomer by the lungs, brain, heart, gut, kidneys or hindquarters. It was concluded that, although the clearances of the enantiomers differed, the total body clearance of both enantiomers was accounted for by hepatic clearance exclusively. There was no evidence of time dependent kinetics. PMID- 1911009 TI - Disposition of mepivacaine and bupivacaine enantiomers in sheep. AB - Mepivacaine and bupivacaine are used clinically as racemic mixtures of enantiomers. In these studies the enantiomers of each agent were administered separately to sheep by i.v. bolus injection on separate occasions. Enantioselective disposition was deemed if the R:S ratio of the relevant pharmacokinetic parameter differed significantly from unity. Both enantiomers of both agents were cleared principally by the liver; urinary excretion of unmetabolized agents accounted for less than 2% of the doses. For R(-)-and S(+) mepivacaine, respective mean (SEM) values of parameters were: total body clearance 1.20 (0.29) litre min-1 and 0.97 (0.20) litre min-1 (ns); total volume of distribution 144 (39) litre and 80 (21) litre (P less than 0.05); slow half life 120 (40) min and 84 (22) min (ns); mean hepatic extraction ratio 0.50 (0.14) and 0.52 (0.09) (ns); mean hepatic clearance 0.75 (0.23) litre min-1 and 0.75 (0.18) litre min-1 (ns). For R(+)- and S(-)-bupivacaine, respective values were: total body clearance 0.77 (0.33) litre min-1 and 0.53 (0.26) litre min-1 (P less than 0.05); total volume of distribution 40 (10) litre and 43 (10) litre (ns); slow half-life 57 (10) min and 104 (21) min (P less than 0.05); mean hepatic extraction ratio 0.46 (0.15) and 0.29 (0.13) (P less than 0.05); mean hepatic clearance 0.85 (0.31) litre min-1 and 0.54 (0.26) litre min-1 (P less than 0.05). Thus there was enantioselective distribution of mepivacaine and enantioselective clearance of bupivacaine, but the magnitude of the effect was relatively small. PMID- 1911011 TI - Inhalation induction of anaesthesia with isoflurane: effect of added carbon dioxide. AB - Fifty children underwent inhalation induction of anaesthesia with isoflurane and nitrous oxide in oxygen with or without the addition of 5% carbon dioxide. Addition of carbon dioxide resulted in more rapid induction and significantly reduced the incidence and severity of airway related problems. PMID- 1911012 TI - Mental function after general anaesthesia for transurethral procedures. AB - We have assessed the influence of age and preoperative mental status score on postoperative mental function, using a choice reaction time test. One hundred and twelve patients (mean age 70 yr, range 48-88 yr) were given a standardized general anaesthetic for transurethral procedures. Mental status before anaesthesia was measured with the Clifton Assessment Procedure for the Elderly (CAPE). Reaction time was measured before anaesthesia and for up to 3 days after anaesthesia. Variability in reaction time performance was increased 24 h after anaesthesia in transurethral patients, but not in a control group of orthopaedic patients (P = 0.0006). Factors contributing to increased variability of reaction time after operation in a multiple regression analysis were reduced CAPE score before operation (P less than 0.0001), extent of surgery (P = 0.023), postoperative pain (P = 0.007) and postoperative sedative drugs (P = 0.009). Factors not contributing included age, diagnosis of cancer, number of previous operations in past 5 years, duration of anaesthesia, minimum mean arterial pressure, minimum and maximum perioperative PCO2 values, postoperative pyrexia and poor sleep. PMID- 1911013 TI - Effects of flumazenil on cerebral blood flow and oxygen consumption after midazolam anaesthesia for craniotomy. AB - Cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMRO2) were measured by a modification of the Kety-Schmidt technique using i.v. xenon-133 in 20 patients undergoing craniotomy for supratentorial cerebral tumours. Anaesthesia was induced and maintained with midazolam, fentanyl and nitrous oxide. Pancuronium was given for neuromuscular block. The lungs were ventilated to normocapnia. The first flow measurements were performed approximately 1 h after induction of anaesthesia. At the end of operation the patients were allocated to two groups. Ten patients were given flumazenil 0.01 mg kg-1 and 5 min later the second flow measurement was performed. In the other 10 patients the second flow measurement was performed before the administration of flumazenil. Plasma concentrations of midazolam were measured at the time of each measurement of CBF. There was no difference between the groups in plasma concentration of midazolam, CBF or CMRO2. Flumazenil had no effect on CBF and CMRO2. PMID- 1911014 TI - Pain on injection of propofol: effects of concentration and diluent. AB - The emulsion formulation of propofol (Diprivan) evokes pain on i.v. injection, although its pH and osmolality are close to those of blood. The pain induced by serial dilutions of propofol in Intralipid and 5% glucose was examined in isolated vein segments and after intracutaneous injection. Propofol evoked pain in a concentration-related manner in six of eight subjects after i.v. perfusion and in all eight subjects after intracutaneous injections. Pain was maximal with propofol 56 x 10(-3) mol litre-1 when visual analogue pain scale was 60% of maximum (range 20-92%) for venous perfusion and 89% (range 66-100%) for intracutaneous injection. Dilution with 10% Intralipid reduced pain more than that with 5% glucose. We conclude that the intensity of pain after i.v. injection of propofol was related to its free aqueous concentration. PMID- 1911015 TI - Comparison of arterial and arterialized venous concentrations of propofol during infusion of propofol. AB - Seven patients received a series of low-dose propofol infusions designed to produce three successive pseudo-steady states of arterial blood concentration: 0.06, 0.17 and 0.43 micrograms ml-1. Arterial and arterialized venous blood samples were obtained simultaneously at the end of each infusion. The results indicate that 95% of the arterialized venous concentrations may be expected to lie within 1 +/- 43% of the corresponding arterial concentration, or -5 +/- 35% if one set of measurements with poor agreement between duplicate aliquots is omitted. PMID- 1911016 TI - Effects of labetalol on perioperative stress markers and isoflurane requirements. AB - We have studied the effect of labetalol on anaesthetic requirements, cardiac and humoral responses in 16 healthy women during elective abdominal surgery. The experimental group (n = 8) received increments of i.v. labetalol 0.15-0.3 mg kg-1 to reduce mean arterial pressure (MAP) by 15% from values obtained before anaesthesia. All patients received thiopentone 6 mg kg-1 and anaesthesia was maintained with isoflurane and nitrous oxide. In the placebo group, tracheal intubation provoked a 33% increase in heart rate (HR) and a 52% increase in MAP (P less than 0.001 vs baseline for both). In contrast, pretreatment with labetalol resulted in a 7.3% increase in HR and a 21.3% increase in MAP (P less than 0.05 vs baseline for MAP). Two patients treated with labetalol had a reduction in MAP to 50-60 mm Hg during surgery. After tracheal extubation, the labetalol group had a significantly slower HR than the placebo group (P less than 0.05). The cardiovascular response to tracheal intubation was associated with an increase in plasma noradrenaline concentration in both groups. Labetalol did not affect isoflurane requirements, plasma concentrations of adrenaline, cortisol and aldosterone or arterial PO2, but prevented the decrease in plasma concentration of potassium which occurred in placebo treated patients (P less than 0.05) in early recovery. We conclude that preanaesthetic administration of labetalol attenuated the perioperative hypertensive and tachycardic responses, but was accompanied by intraoperative hypotension when given in doses greater than 0.5 mg kg-1, despite an increase in plasma noradrenaline concentrations. PMID- 1911017 TI - Effect of single doses of cisapride and ranitidine administered simultaneously on plasma concentrations of cisapride and ranitidine. AB - We have studied in 12 volunteers the effect of single doses of cisapride and ranitidine, administered simultaneously, on plasma concentrations of cisapride and ranitidine. Median maximum plasma concentration of ranitidine was achieved 1 h earlier when ranitidine was taken with cisapride compared with ranitidine alone (P = 0.012). There was a 24% decrease in plasma ranitidine AUC8h when ranitidine was taken with cisapride compared with ranitidine alone (P less than 0.005). Ranitidine had no effect on absorption of cisapride. PMID- 1911018 TI - Effects of extradural anaesthesia on umbilical and uteroplacental arterial flow velocity waveforms. AB - Flow velocity waveforms were recorded from the umbilical artery and uteroplacental arterial circulations of 15 women undergoing elective Caesarean section under extradural anaesthesia. The systolic: diastolic ratios of the flow velocity waveform were determined before and after extradural block. Extradural block did not alter fetal or maternal heart rates; however, umbilical artery systolic:diastolic ratio decreased from a mean (SD) of 2.4 (0.42) to 2.26 (0.38) (P = 0.049). There were no significant changes in the uteroplacental systolic:diastolic ratios. These results were compared with those from a control group in which no statistically significant changes in maternal and fetal systolic:diastolic ratios or heart rates were observed. The application of a pulse correction factor to standardize the data to fixed maternal and fetal heart rates had little effect on the significance of the findings. Extradural block in normal pregnant women during late gestation was associated with a small reduction in umbilical artery systolic:diastolic ratios, suggesting a decrease in downstream fetoplacental vascular resistance. PMID- 1911019 TI - Pharmacokinetics and distribution of ketamine after extradural administration to dogs. AB - We have studied the pharmacokinetics and distribution of ketamine and its biotransformation products in dogs after extradural administration of ketamine at L4-5. The mean apparent uptake rate constants of ketamine for plasma and CSF were 4.17 (SD 1.84) and 5.15 (2.50) h-1, respectively. The concentrations of ketamine in CSF were greater than those found in plasma. The elimination half-life values of the parent drug for both biological fluids were similar (4.3 (2.96) h and 4.6 (3.31) h for plasma and CSF, respectively). The apparent formation rate constant of norketamine was greater than that of dehydronorketamine. However, the concentrations of the biotransformation products in CSF were smaller than those of the parent drug. These results are similar to the distribution of ketamine and its metabolites in different cerebral structures and tissues. The concentrations decreased in concert with the increase in polarity of the metabolites. A specific distribution for all compounds was observed. Ketamine showed a greater affinity for brainstem, while norketamine and dehydronorketamine were distributed mostly in cerebellum and kidney, respectively. PMID- 1911020 TI - Postoperative myocardial ischaemia in patients with recent myocardial infarction. AB - Fifteen patients (10 men and five women; mean age 67.3 yr) with a history of a recent (less than 1 yr) myocardial infarction underwent ambulatory ECG monitoring for 5 days after non-cardiac surgery. The duration, number and severity of ischaemic episodes were maximal within the first 12 h after surgery and again on the 3rd day after operation. The difference in the duration of ischaemic episodes between the 2nd and 3rd days after operation was statistically significant (P less than 0.05). There were no perioperative myocardial infarctions and all patients were discharged from hospital. PMID- 1911021 TI - The loading dose in continuous infusion extradural analgesia in obstetrics. AB - We have investigated the need for a loading dose of local anaesthetic before continuous extradural analgesia. After a standard test dose, patients received 0.08% bupivacaine 8 ml, isotonic saline 8 ml or nothing. A continuous infusion of 0.08% bupivacaine 20 ml h-1 was then commenced. The mean times to onset of satisfactory pain relief were similar in the first two groups, but prolonged significantly in the third. This group also required more interventions for inadequate analgesia, although not significantly so. Mean time to achieve highest level of block was significantly shorter in the first group. PMID- 1911022 TI - Haemodynamic effects of periodic ventilation: abolition with supplementary oxygen. AB - A 63-yr-old man was noted to breathe with a periodic pattern of ventilation during sleep, both before and after operation for coronary artery grafting, and 6 weeks later after aortic aneurysm repair. Periodic ventilation was associated with cyclic oxygen desaturations and increases in heart rate and arterial pressure. Administration of oxygen was found to abolish consistently the periodic pattern and the associated haemodynamic changes. PMID- 1911023 TI - Controlled hypotension for cerebral aneurysm surgery in the presence of severe aortic coarctation. AB - A patient is described with a bicuspid aortic valve and an undiagnosed aortic coarctation, presenting with a subarachnoid haemorrhage. A cerebral aneurysm was clipped under controlled hypotension. In view of the risk of inducing severe hypotension in the distal aorta in this patient, femoral arterial pressure was monitored. A marked reduction in the radial-femoral arterial pressure gradient during controlled hypotension was noted. PMID- 1911024 TI - Compartment syndrome after pressurized infusion. PMID- 1911025 TI - Dilutional hyponatraemia following transurethral operation for clot retention. AB - Dilutional hyponatraemia with symptoms (TUR syndrome) may occur not only in association with transurethral prostatic resection, but also in other operations in which electrolyte-free irrigating fluid is used. This case report describes a patient who developed the TUR syndrome after blood clots had been removed from the bladder with the aid of a transurethral resectoscope. PMID- 1911026 TI - AURA: a new respiratory monitor and apnoea alarm for spontaneously breathing patients. AB - Previous attempts to introduce non-invasive monitoring of ventilation of spontaneously breathing patients into routine practice have been unsuccessful. The Aberdeen University Respiratory Alarm (AURA) allows such monitoring by utilizing the pyroelectric property of polarized polyvinylidine fluoride sensors to detect temperature changes that occur during breathing into an oxygen delivery face mask. A quartz crystal oscillator generates pulses that allow measurement of interexpiratory time and ventilatory frequency. The system incorporates LED digital displays, a bargraph and audiovisual alarms. An analog output permits display and analysis of the sensed signals. AURA performed satisfactorily in both volunteer studies and six patients in the clinical setting. AURA may be an appropriate respiratory transducer in those patients requiring oxygen therapy. PMID- 1911027 TI - A new optical transducer for arterial pressure measurement. AB - A new optical pressure transducer system (Viggo) has been assessed and compared with a standard P10 transducer (Spectramed) using a similar 20-gauge cannula, both in vitro in terms of linearity and frequency response and in vivo using an animal model. The linearity of the transducers was comparable; the resonant frequencies were 106 Hz and 75 Hz, respectively. However, the resonant frequency of the complete Spectramed system including 150-cm tubing was 11 Hz. The frequencies at which the output amplitude error exceeded 10% of the initial amplitude for the Viggo and for P10 with and without 150-cm tubing were 32 Hz, 24 Hz and 4 Hz, respectively. The principal advantage of the new transducer is that it is sufficiently compact to be mounted directly in the cannula at the wrist, so obviating the use of connecting tubing between the transducer and the cannula. PMID- 1911028 TI - The first year's experience of an acute pain service. AB - The benefits, risks and resource implications of providing an Acute Pain Service were assessed during the first year of the service. Six hundred and sixty patients recovering from major surgery were treated with patient-controlled analgesia (510 patients) or extradural infusion analgesia (150 patients). The results of a prospective outcome study showed that pain control was good: more than 60% of patients scored their pain as mild during the first 24 h. Only 10% of patients complained of severe postoperative pain. Eight patients developed potentially serious complications including respiratory depression and hypotension; the diagnosis and management of these problems on general wards is discussed. Retrospective analysis of the incidence of postoperative chest infection in surgical patients showed a marked reduction during the first year of the service (1.3% in 1988, 0.4% in 1989-90 (P less than 0.01]. PMID- 1911029 TI - Anaesthetic equipment for a developing country. PMID- 1911030 TI - Spinal needles. PMID- 1911031 TI - Toxicity and pharmacokinetics of morphine and morphine-6-glucuronide. PMID- 1911032 TI - Tissue viability. Managing the patient with fractured femur. PMID- 1911033 TI - Tissue viability. Calcium alginate: a dressing trial. PMID- 1911034 TI - Tissue viability. Toe-nail avulsion. PMID- 1911035 TI - Retinoic acid in acute promyelocytic leukemia: the promise and the paradox. AB - Acute promyelocytic leukemia (APL) is a particularly virulent subtype of acute myeloid leukemia that is associated with a specific chromosomal translocation, t(15;17). Patients with APL are currently being managed with cytolytic chemotherapy (usually an anthracycline in combination with arabinosylcytosine), a treatment that can induce complete remissions in 65% or more of patients and probably cure 15% or more. Exciting new clinical observations have shown that patients with APL also respond extremely well to treatment with all-trans retinoic acid, an agent which induces the leukemic promyelocytes to undergo maturation and lose their ability to proliferate. Retinoic acid by itself is not curative, but by combining it with cytolytic chemotherapy, it may be possible to cure the majority of patients with this previously fatal leukemia. Interestingly, independent molecular studies have recently revealed that the breakpoint of t(15;17) lies within the gene encoding the retinoic acid receptor-alpha (RAR alpha) on chromosome 17q21, and that patients with APL express aberrant forms of the RAR-alpha transcript. This convergence of clinical and molecular observations, though fortuitous, is extremely important because it represents the first example of a selective form of treatment for a human leukemia that is related to a specific genetic abnormality. PMID- 1911036 TI - Recognition of malignant cells by antibodies to the T-cell antigen receptor: potential for diagnosis. PMID- 1911037 TI - The fibroblast growth factor family. PMID- 1911038 TI - Biological response modifiers in the treatment of cancer and infectious diseases. PMID- 1911040 TI - Genetically modified tumor-infiltrating lymphocytes for cancer therapy. PMID- 1911041 TI - Molecular and cellular biology of antigen processing and presentation. PMID- 1911039 TI - Tumor metastasis and nm23: current concepts. AB - Reduced expression and/or somatic allelic deletion of nm23 is associated with high metastatic potential in several types of rodent tumors and human breast and colorectal carcinomas. Transfection of murine nm23-1 cDNA into highly metastatic murine K-1735 TK melanoma cells results in a reduced incidence of primary tumor formation, significant reduction in tumor metastatic potential, and altered responsiveness to the cytokine, transforming growth factor beta. Here we discuss emerging concepts concerning nm23, such as its varied pattern of alteration/expression in tumor metastasis, its effect on tumorigenesis, and its possible biochemical functions. PMID- 1911042 TI - Epithelial cancers of the aerodigestive tract: biology, prevention, and therapy. PMID- 1911043 TI - Activation of the rasHa gene in urethane-initiated papillomas induced by protocols with high and low frequencies of malignant conversion. AB - The number of papillomas that develop in mice initiated with a single exposure to urethane and promoted by repeated applications of 12-O-tetradecanoylphorbol-13 acetate (TPA) is increased greater than 4-fold by pretreating the skin once with TPA 24 hr before administration of urethane. In contrast, the carcinoma incidence was increased only 2-fold by the TPA pretreatment. Individual papillomas developed from the two protocols, differing in the potential for conversion to malignancy, were compared for activation of the rasHa gene. An activated oncogene that transformed 3T3 cells was found in the DNA of four of five papillomas from urethane-initiated, TPA-promoted mice and in eight of eleven papillomas from similarly promoted mice exposed to TPA before urethane initiation. Southern analysis of DNA from tumors or 3T3 foci demonstrated that the rasHa gene was activated by an A----T transversion at the second base of codon 61 in all mutated alleles. Thus, tumors induced by the two protocols did not differ in rasHa activation. PMID- 1911044 TI - Red cell regulation of tumor necrosis factor-induced human neutrophil cytostatic activity. AB - Tumor necrosis factor (TNF) activates polymorphonuclear neutrophils (PMN) to suppress tumor cell proliferation. This cytostatic activity could be blocked by the addition of red blood cells (RBC) into the assay. TNF-induced PMN cytostatic activity was mediated by hydrogen peroxide (H2O2). RBC have two major pathways to detoxify H2O2, one by catalase and the other by the glutathione redox cycle. Therefore, the catalase inhibitor 3-amino-1,2,4-triazole (AT) and the glutathione inhibitor N-ethylmaleimide (NE) were used to assess the role of each anti-oxidant in protecting the tumor target cells. RBC, depleted of catalase by AT, no longer protected Raji tumor cells from PMN cytostatic activity. However, depletion of reduced glutathione by NE had no effect on RBC protection of tumor target cells. Thus, RBC can protect tumor cells from cytostatic activity mediated by TNF activated PMN, and the protection is a function of catalase, but not glutathione. PMID- 1911045 TI - In vivo studies by magnetic resonance imaging and spectroscopy of the response to tamoxifen of MCF7 human breast cancer implanted in nude mice. AB - Magnetic resonance 1H-imaging and 31P-localized spectroscopy were utilized to monitor, noninvasively, MCF7 human breast cancer tumors implanted in immunodeficient mice. The tumors were followed during estrogen dependent growth and tamoxifen induced remission. Early after tamoxifen administration enhanced necrosis developed, extending to most of the tumor volume. This was followed by growth of repair tissue along with tumor regression. The short-term tamoxifen treatment also modified the content of the phosphate metabolites, increasing the nucleoside triphosphate to inorganic phosphate ratio from 0.41 +/- 0.15 (n = 14) before treatment to 1.10 +/- 0.70 (n = 8, P less than 0.025) and to 1.75 +/- 0.66 (n = 9, P less than 0.0002) 4-7 days and 9-19 days, respectively, after treatment. This change was attributed to the growth of reparative tissue. The results provide new information regarding the response and the mechanism of action of tamoxifen. PMID- 1911047 TI - Drug chirality: impact on pharmaceutical regulation. PMID- 1911046 TI - Role of xanthine oxidase in the potentiation of doxorubicin-induced cardiotoxicity by mitomycin C. AB - Clinical evidence has suggested that mitomycin C (MMC) potentiates doxorubicin (DOX) induced cardiotoxicity. In this study a mouse model was used to examine the effect of DOX on the ability of cardiac tissue to bioactivate MMC to generate oxygen radicals. Cardiac damage was assessed by measuring serum CPK-MB isoenzyme levels and thiobarbituric acid reactive substances (TBARS) in the cardiac tissue. The exposure of animals to DOX or DOX and MMC over a three week period led to an increase in serum CPK-MB isoenzyme levels as well as TBARS. Treatment with DOX led to an increase in MMC-dependent, NADH-dependent, cyanide insensitive oxygen consumption, compared to control animals, thereby suggesting increased MMC dependent oxygen radical generation. Levels of xanthine oxidase (XO; EC 1.1.3.22) and NADPH:cytochrome C reductase, two enzymes known to bioactivate MMC with subsequent oxygen radical generation, were measured in cardiac tissue with a 4.5 x increase in XO activity seen in DOX treated animals vs controls and no change in NADPH:cytochrome C reductase activity. Cardiac levels of xanthine dehydrogenase (XDH; EC 1.1.1.204) activity in DOX treated animals decreased while the XO/XDH ratio increased, suggesting a conversion of XDH to XO following DOX treatment. PMID- 1911048 TI - Pharmacokinetics of ibuprofen enantiomers in dogs. AB - Inversion of inactive (R)-ibuprofen to active (S)-ibuprofen has been suggested to occur presystemically only. In order to investigate the site of inversion in dogs we administered both enantiomers either intravenously or intraduodenally (10 mg/kg) to adult, male beagle dogs (n = 3) in a crossover design. Plasma, urine, and bile were collected for up to 6 h and analyzed stereospecifically by HPLC, according to a previously published method. Pharmacokinetic parameters were calculated using a linear computer program. Absorption after intraduodenal administration occurred rapidly, resulting in maximum plasma concentrations 0.2 h after giving the enantiomer. Approximately 70% of the (R)-enantiomer (according to AUC) was inverted to the S-enantiomer independent of route of administration. No R-ibuprofen could be detected in plasma after (S)-ibuprofen administration. Mean residence time was found to be 2 to 3 times longer for (S)- than for (R) ibuprofen. Total systemic clearance from plasma was twice as high for (R)- than for (S)-ibuprofen. There were no differences between plasma clearances after intravenous and intraduodenal administration. Between 8 and 17% of dose was recovered in bile [especially as free and conjugated (S)-ibuprofen] and 3-12% in urine [as (S)-ibuprofen, hydroxy- and carboxyibuprofen, free and conjugated forms]. Small amounts of (R)-ibuprofen were detected in bile after intraduodenal administration of (R)-ibuprofen only (1.8% of dose). In short, the unidirectional inversion of R-ibuprofen appears to occur systemically rather than presystemically in dogs. PMID- 1911049 TI - A new model to account for the order in which enantiomers of alkylarylcarbinols elute from a Pirkle chiral HPLC column: preparation, absolute stereochemistry, and chromatographic properties of (+)-1,2-benzocyclononen-3-ol and (+)-1,2 benzocyclodecen-3-ol. AB - Samples enriched in (-)- and (+)-1,2-benzocyclononen-3-ol were prepared by microbially mediated reactions. An enriched sample of (+)-1,2-benzocyclodecen-3 ol was prepared by fractional crystallization of the diastereoisomeric camphanates, followed by hydrolysis. The absolute stereochemistry of both alcohols was established by chemical transformations. The elution order of their enantiomers from a chiral Pirkle HPLC column [(R)-N-(3,5-dinitrobenzoyl)phenyl glycine ionically bound to gamma-aminopropyl silanized silica] was determined. The information in conjunction with other data was used to formulate a rule to predict the configuration of an enantiomer of an alkylarylcarbinol from its elution order from this column. PMID- 1911050 TI - N,N-dimethylcarbamyl derivatives of oxazepam. AB - Three N,N-dimethylcarbamyl derivatives of oxazepam (1-(N,N dimethylcarbamyl)oxazepam, 3-O-(N,N-dimethylcarbamyl)oxazepam, and 1,3-O-bis(N,N dimethylcarbamyl) oxazepam) and a 3-O-acyl-1-(N,N-dimethylcarbamyl)-oxazepam were synthesized from either oxazepam or demoxepam. Enantiomeric pairs of these derivatives and of camazepam were resolved by high-performance liquid chromatography on at least two of three commercially available chiral stationary phase columns employed. Absolute configurations of resolved enantiomers were established by comparing their circular dichroism spectra to those of enantiomeric oxazepams with known absolute stereochemistry. Similar to those of oxazepam, enantiomers of 1-(N,N-dimethylcarbamyl)oxazepam undergo rapid racemization (t1/2 1.9 min at 23 degrees C and 0.9 min at 37 degrees C) in an aqueous solution at pH 7.5. The (R)-enantiomer of rac-3-O-acyl-1-(N,N dimethylcarbamyl)oxazepam was hydrolyzed approximately 4.6-fold faster than the (S)-enantiomer by esterases in rat liver microsomes, whereas the (S)-enantiomer was hydrolyzed approximately 43-fold faster than the (R)-enantiomer by esterases in rat brain S9 fraction. PMID- 1911051 TI - New clinical and radiographic features of the seronegative spondyloarthropathies. AB - This article reviews new data supporting the hypothesis that the clinical spectrum of the seronegative spondyloarthropathies is wider than previously realized. It describes the literature in general and specific reports on the prevalence and clinical features of seronegative spondyloarthropathies in a number of different populations from America and Asia. Undifferentiated or unclassified spondyloarthropathies are now recognized more frequently. There is an extensive analysis of new proposals for nomenclature and criteria for classification that need to be validated. The normal appearance and biomechanics of the sacroiliac joints as well as new imaging techniques to approach them in several diseases are also discussed. Clinical, radiographic, and histopathologic findings in spinal disease and further observations on gut inflammation and intestinal permeability are also presented here. A long list of clinical associations of the seronegative spondyloarthropathies is also given. PMID- 1911052 TI - Gastrointestinal-related arthritis and psoriatic arthritis. AB - Psoriatic arthritis and the enteropathic arthropathies are included among the seronegative spondyloarthropathies. The concept of psoriatic arthritis as a specific entity continues to be challenged by some investigators, while others report on additional findings in this condition, such as temporomandibular joint disease. The etiopathogenesis of the condition continues to be investigated by the exploration of genetic and immunologic factors. Treatment options include dietary manipulations. The prevalence of arthritis among patients with bowel disease seems to be increasing, while the presence of gut lesions among patients with spondyloarthropathy is noted to be associated with disease activity. PMID- 1911053 TI - Infectious agents and other nongenetic immunologic factors in spondyloarthropathies. AB - Because one of the spondyloarthropathies, reactive arthritis, is induced by infections, research into the role of arthritis-causing bacteria has been strongly emphasized. The most remarkable finding in recent years is the detection of some of the bacterial components in the articular compartment, in some cases even several years after the development of arthritis. This location would account for the fact that T lymphocytes in the synovial compartment demonstrate a high in vitro response to preparations of the arthritis-causing bacteria. The persistence of these bacterial components would explain the frequently reported prolonged antibacterial antibody response in arthritis patients. Although the factors leading to the location and persistence of the bacteria are not clear, the finding provides a rationale for treating these patients with long-term antibiotics. A major question being investigated is how the presence of bacterial components in the articular compartment is related to the predominance of HLA-B27 in many of the patients. PMID- 1911054 TI - Genetics of the spondyloarthropathies. AB - Following three decades of study of the genetics of the spondyloarthropathies by segregation analysis of families, research has increasingly made use of new methods of molecular genetics and immunology. In the past year, most attention has been given to the structure and function of HLA-B27, which, with its various subtypes, is the major phenotype contributing to susceptibility to this group of disorders. Structural studies have revealed which structures are responsible for the common antigenic properties and which are responsible for subtype specificities. Application of increasing understanding of the function of class I HLA antigens is permitting the development of various models of disease. Successful production of HLA-B27 transgenic animals holds promise for testing these models. PMID- 1911055 TI - Bacterial arthritis. AB - In this review of the 1990 septic arthritis literature, we revisit synovial fluid leukocytosis, examine the utility of synovial fluid glucose and protein measurements, and look at the levels of two cytokines, tumor necrosis factor and interleukin-1, in infected joint fluids. We see the many faces of gonococcal arthritis and the ravages of septic arthritis when the host has rheumatoid arthritis. Should we recommend antibiotic prophylaxis for the rheumatoid patient with a prosthetic joint who is undergoing a procedure that leads to transient bacteremia? What are some of the salient features of septic arthritis when it involves the sternoclavicular or sacroiliac joints? We also look at some unusual microorganisms, eg, group C Streptococcus, Streptococcus viridans, Listeria monocytogenes, Pseudomonas cepacia, Pseudomonas maltophilia, and Neisseria sicca. In patients with acquired immunodeficiency syndrome, we encounter reports of septic arthritis, osteomyelitis, and spinal epidural abscess caused by opportunistic microorganisms. Two unusual sites of infection include the C1-2 lateral facet joint and subacromial bursa without involvement of the glenohumeral joint. Finally, we examine how to drain a septic knee: the orthopedic point of view. PMID- 1911056 TI - Pathogenesis, diagnosis, manifestations, and treatment of Lyme disease. AB - Progress in understanding the causation and immunopathogenesis of Lyme disease has continued in the past year. Only by studying the complex relationship between the infecting organism, Borrelia burgdorferi, and the host will improvements in therapy be possible. Physicians in the United States have evaluated large numbers of patients with late neurologic Lyme disease, and a more consistent clinical description of the North American experience is emerging. Laboratory diagnosis remains a problem. Improvements are being made in both the sensitivity and specificity of existing tests and also in the selection of appropriate patients by physicians. Both of these factors will improve predictive value. PMID- 1911057 TI - Arthritis due to tuberculosis, fungal infections, and parasites. AB - Tuberculous, fungal, and parasitic infections infect millions of people throughout the world. While other problems usually overshadow their rheumatologic manifestations, nearly all these infections can involve bone or joints and may on occasion present with rheumatologic symptoms. The classic model of these diseases presenting as chronic monoarticular arthritis is still generally valid but other presentations, such as tenosynovitis with atypical mycobacterial infections, erythema nodosum with leprosy, coccidioidomycosis and histoplasmosis, and reactive arthritis with schistosomiasis and helminthic infections, are now well established. The most dramatic change in the epidemiology of tuberculous infections in recent years is the increasing incidence in patients with the acquired immunodeficiency syndrome (AIDS). Mycobacterium avium complex infections in particular have increased dramatically and are a major problem in the later stages of AIDS. Reports of septic arthritis and tenosynovitis due to M. avium are likely to increase over the next few years. PMID- 1911058 TI - Infected arthroplasties. AB - Infection is potentially the most serious complication of total joint arthroplasty. Over the last 10 years, considerable advances have been made in the diagnosis and management of the infected implant. Modern methods of treatment are successful in up to 90% of cases in the lower limb, and results appear to be improving in the upper limb. This review places recent advances in the context of previous published work in the field. PMID- 1911059 TI - Infectious arthritis in primary disorders of immunoglobulin synthesis. AB - Disorders of immunoglobulin synthesis are of great interest to rheumatologists. At the diagnostic level, such disorders not uncommonly mimic commoner rheumatic diseases, so it is important that the diagnostic possibility of immunodeficiency be kept in mind. Infections often complicate immunodeficiency and may present in an atypical manner. From the theoretical standpoint, the interactions between infectious agents and patients with impaired immunity suggest ways in which the same or similar agents could be responsible for arthritis of unknown etiology. Furthermore, many immunodeficiency disorders predispose to autoimmunity; establishing the mechanism of this association may offer good insights into the factors that trigger autoimmune disorders in patients with seemingly normal immune competence. PMID- 1911060 TI - Clinical features of osteoarthritis, diffuse idiopathic skeletal hyperostosis, and hypermobility syndromes. AB - In 1990, there were signs of a renewed interest in clinical studies about several aspects of osteoarthritis. The work-up of classic data and the use of new information from epidemiologic surveys as well as careful radiographic monitoring of selected groups of patients have brought us broader views on the general course of the condition. In addition, the biochemical disturbances underlying certain types of early degenerative arthritis that could help us to understand some of the mechanisms that may be operative in osteoarthritis have been disclosed. Finally, a few pieces of new information have been incorporated into the knowledge of diffuse idiopathic skeletal hyperostosis and the hypermobility syndrome. PMID- 1911061 TI - Epidemiology and genetics of osteoarthritis. AB - Osteoarthritis is the most common of the arthropathies. Previous population-based epidemiologic studies have estimated the prevalence of osteoarthritis by age, gender, race, and site in many populations. Cross-sectional and retrospective data from these prevalence surveys have been analyzed to identify possible risk factors for the development of osteoarthritis at specific sites. Data from prospective population-based epidemiologic studies including the Framingham Osteoarthritis Study, the Tecumseh Community Health Study, the National Health and Nutrition Examination Survey I Epidemiologic Followup Study, and the Baltimore Longitudinal Study of Aging are being analyzed to estimate the incidence of osteoarthritis by age, gender, and site, and the prognosis of subjects with osteoarthritis at specific sites in terms of morbidity and mortality, as well as to confirm the association of risk factors with the development and progression of osteoarthritis by site. Additionally, the application of techniques of molecular biology to the study of the genetics of familial osteoarthritis has identified hereditary defects in type II collagen that appear to predispose to the early development of osteoarthritis in affected family members. Results of these studies highlight opportunities for the primary and secondary prevention of osteoarthritis. PMID- 1911062 TI - Cartilage research, biochemical, histologic, and immunohistochemical markers in cartilage, and animal models of osteoarthritis. AB - Over the past 20 years, there has been growing interest in the biochemistry, molecular biology, and physiology of cartilage. In the last year, there have been considerable advances in the understanding of the processes involved in the anabolism and breakdown of cartilage and the influence of cytokines and growth factors. This review addresses the area of cartilage research, the investigation of markers of cartilage, and the biochemical mechanisms involved in the development of osteoarthritis in animal models. The volume of cartilage research is extensive, and due to the nature of this review, I concentrate on work that is directly related to the anabolic and catabolic response of cartilage to various agents and to those investigations of cartilage with particular relevance to the development of osteoarthritis both in experimental models and in humans. PMID- 1911064 TI - The seronegative spondyloarthropathies. PMID- 1911063 TI - Gout and hyperuricemia. AB - Although our understanding of hyperuricemia and gout has changed little over the past several years, questions remain in defining the many metabolic abnormalities that can result in these problems. In the past year, several papers have further addressed heritable mechanisms for the development of hyperuricemia, as well as environmental factors that contribute to its onset in adulthood. Consequences of hyperuricemia other than clinical gout have received further attention. Although typical gout is easily recognized and treated, several recent papers have addressed atypical presentations of gout, as well as other causes of podagra that might have been attributed previously to gout. The treatment of patients whose disease is uncomplicated by other conditions remains straightforward. However, the presentation of gout in patients with multiple comorbidities not only increases recognition of the toxicity of nonsteroidal anti-inflammatory drugs and colchicine, but often requires innovative approaches to its treatment. PMID- 1911065 TI - Infectious arthritis and immune dysfunction. PMID- 1911066 TI - Osteoarthritis and crystal deposition diseases. PMID- 1911067 TI - Cholera vaccine evaluation. PMID- 1911068 TI - Environmental health conditions and cholera vulnerability in Latin America and the Caribbean. PMID- 1911069 TI - [Reconstructive microsurgery of the seminal ducts and extempore testicular biopsy]. PMID- 1911070 TI - [Risk surgery of the carotid. A balanced assessment of the use of locoregional anesthesia]. AB - The authors report their experience with regional anaesthesia in carotid surgery. They performed 80 carotid endarterectomies in 79 patients. Thirty-three patients were at high surgical risk because of contralateral internal carotid artery occlusion or bilateral stenosis (greater than 70%) or ischemic brain areas for past stroke. In this high risk group 4 strokes were registered in the postoperative period, while no strokes appeared in patients non at risk. PMID- 1911071 TI - [Spontaneous rupture of the esophagus]. AB - The authors relate upon the so-called Boerhaave's syndrome or spontaneous perforation of the esophagus illustrating 2 cases recently observed. On the basis of their experience and of what has been reported by the literature on this subject the etiopathogenetic and pathophysiologic problems as well as the adequate treatment are debated. Particularly the nature of the lesion, which is a barotrauma lesion, the urgency of the surgical treatment, and the severity of the prognosis are pointed out. PMID- 1911073 TI - [Complete rupture of the pregnant uterus: treatment results in 18 cases]. PMID- 1911072 TI - [The treatment of nonpalpable breast lesions. Our experience]. AB - Thanks to the diffusion of the clinico-mammographic screening, in the last ten years a considerable increase of breast carcinomas diagnosed in a subclinical stage has been registered. The authors report the preliminary results of their experience in nonpalpable lesions of the breast and confirm the validity of conservative surgery for their treatment. Nonpalpable breast carcinomas must be considered as an early stage of palpable T1 tumors, for which validity of conservative surgery is largely demonstrated. Moreover, results are not compromised by possible multicentricity and/or positivity of axillary lymph nodes. PMID- 1911074 TI - [Hemolytic jaundice in anaerobic bacteremia. A report of a case resolved surgically]. AB - The authors report a case of haemolytic jaundice caused by anaerobic bacteria arising from an abdominal abscess. This is undoubtedly a rare pathology but, when occurring, the resolution may be achieved by surgical therapy. PMID- 1911075 TI - [Primary "small-cell" lymphoma of the lung. A clinical case report]. AB - Primary lymphoma of the lung is a rare pathological condition arising from mucosa associated lymphoid tissue (MALT). The lack of specific symptoms and the related diagnostic problems induced the authors to report a clinical case recently observed. Therefore, some histopathologic characteristics useful for a correct differential diagnosis with the pseudolymphoma of the lung and the interstitial lymphocyte pneumonia are analysed. PMID- 1911076 TI - [The criteria for choosing the surgical approach to cervicomediastinal goiters]. AB - The retrospective analysis of a series of 350 cases of intrathoracic goiters, out of a total of 5,000 thyroid operations derived from the joined case records of the 3rd General Surgery Institute (Director: Prof. G. Di Matteo) and the 8th Chair of Surgical Pathology (Director: Prof. F.P. Campana), has induced the authors to reconsider the surgical approach to this pathology on the basis of anatomo-surgical factors. PMID- 1911077 TI - [Spinal anesthesia in the surgery of inguinocrural hernias]. AB - The experience in the surgical treatment of inguinal and crural hernias with epidural and subarachnoidal anaesthesia over a period of fifteen years (1976 1989) is reported. Results obtained in 1,283 cases confirm the validity of the technique and the clinical course suggests that it could well be applied to cardiopathic, hypertensive, obese, bronchopneumopathic patients as well as to dysmetabolic diseases. Furthermore, advantages of spinal anaesthesia compared to general and local anaesthesia are emphasized. The use of ultrathin needles (24 gauge) in performing subarachnoidal anaesthesia is recommended to prevent headache. PMID- 1911079 TI - [The use of the TA-55 mechanical suturing device in the closure of the cecostomy. The authors' experience]. AB - The authors confirm the actuality and validity of decompressive cecostomy in emergency treatment of large bowel obstructions. Taking into account that staplers have substantially reduced the rate of complications and inconvenient of gastrointestinal surgery, their use of cecostomy closure is proposed. Advantages obtained with this technique, namely lack of infections and incisional hernias, are underlined. PMID- 1911080 TI - Quantification of microbial populations associated with the manufacture of vacuum packaged, smoked vienna sausages. AB - Sources of contamination of vacuum-packaged vienna sausages by spoilage microorganisms were examined in a meat-processing plant. Microbial numbers present in the environment, on working surfaces and workers' hands and aprons were quantified by plate counting on selective media. Product line samples were taken at critical control points in the manufacturing process and analysed before and after preliminary incubation of vacuum-packaged samples at 25 degrees C for 24 h. In all samples the numbers of aerobic bacteria, Enterobacteriaceae, lactic acid bacteria and yeasts were determined by standard procedures. Contamination of sausage surfaces by lactic acid bacteria occurred as a result of the manufacturing and handling processes. The environment and specifically packers' hands, as well as working surfaces contributed to microbiological contamination of various types after removal of the peel from individual sausages. The preliminary incubation procedure allowed detection of low numbers of spoilage microorganisms. PMID- 1911078 TI - [Cancer of the breast and the receptor status]. AB - Correlation between survival and hormonal receptor status in patients with breast cancer is still controversial. The results of a study carried out, from 1973 to 1988, on 55 patients (average age 56.7) affected with breast cancer and submitted to radical (Halsted) mastectomy, are reported. Estradiol receptors (ER) and progesterone receptors (PR) were determined using the dextran-coated charcoal (DCC) method and the enzymatic immuno assay (EIA). The threshold value for defining the ER positivity was 10 f/mole/mg of cytosol protein and 50 f/mole/mg for PR positivity. Forty-one patients resulted as ER+, 31 were also PR+. Moreover, 41 patients were treated with tamoxifen (10 mg x 2 die per os). In a 15 year follow-up, no significant difference in survival rate between patients with receptor-positive tumors or treated with tamoxifen and patients with receptor negative tumors was recorded. PMID- 1911081 TI - Mycoflora and toxigenic Aspergillus flavus in Spanish dry-cured ham. AB - Sixty-five dry-salted hams were analysed. Aspergillus and Penicillium were the dominant genera. In general, the mould flora was dominated by Aspergillus spp. and primarily A. glaucus, A. fumigatus, A. niger and A. flavus. A flavus was found in 16 hams and 9 out of 16 strains examined produced aflatoxins 'in vitro'. Surface samples of dry-salted hams showed growth of inoculated A. parasiticus NRRL-2999 strains and production of aflatoxins in low levels at 25 and 30 degrees C. It is concluded that the presence of toxigenic strains in Spanish dry-salted ham does not constitute a health risk. PMID- 1911082 TI - Some taxonomical characteristics of encapsulated Lactobacillus sp. KPB-167B isolated from kefir grains and characterization of its extracellular polysaccharide. AB - A capsular polysaccharide-producing strain KPB-167B isolated from kefir grains was identified as a homofermentative Lactobacillus. The carbohydrate fermentation pattern and DNA base composition of the strain were different from those of other capsular Lactobacillus species previously isolated from kefir grains. The polysaccharide produced by Lactobacillus sp. KPB-167B was found similar to kefiran by 13C-NMR and methylation analysis. Lactobacillus sp. KPB-167B could grow and produce capsular polysaccharide in MRSL medium with better yield than L. kefiranofaciens, which suggested that it is suitable for kefiran production. PMID- 1911083 TI - ELISA screening of staphylococcal enterotoxins by means of a specially developed test kit. AB - The development of a new test kit for the detection of staphylococcal enterotoxins is described. This polyclonal antibody-based enzyme-linked immunosorbent assay (ELISA) is designed for qualitative and quantitative rapid detection of toxin serotypes A, B, C (subgroup 1), D and E in one test system. Results are obtained in 60 min. The lower limit of detection is 0.5 ng/ml; the precision is 90%. PMID- 1911084 TI - Changes in chemical composition and sensory qualities of peanut milk fermented with lactic acid bacteria. AB - The effects of fermentation of aqueous extracts of peanuts (peanut milk) with Lactobacillus delbrueckii ssp. bulgaricus and Streptococcus salivarius ssp. thermophilus, separately and in combination, on selected chemical and sensory qualities were investigated. Changes in pH, titratable acidity and viable cell populations indicated that there was a synergistic interaction between L. delbrueckii ssp. bulgaricus and S. salivarius ssp. thermophilus during fermentation. Analysis of headspace volatiles revealed that hexanal, which is one of the compounds responsible for undesirable green/beany flavor in peanut milk, completely disappeared as a result of fermentation. S. salivarius ssp. thermophilus was more effective than L. delbrueckii ssp. bulgaricus in reducing the hexanal content. The acetaldehyde content of peanut milk increased during fermentation. Changes in concentrations of these volatile compounds were correlated with sensory evaluation scores which showed that a significant (P less than or equal to 0.05) decrease in green/beany flavor and a significant increase in creamy flavor occurred as a result of fermentation. PMID- 1911085 TI - Comparison of lactococcal bacteriophage isolated in the United States and Argentina. AB - Bacteriophage of Lactococcus lactis ssp. lactis and ssp. cremoris, isolated in the United States and Argentina, were compared with respect to host range, adsorption, latent period, burst size and immunological cross-reactivity. Only 1 out of 13 U.S. culture isolates was sensitive to Argentinian phage. Argentinian L. lactis ssp. lactis C2 mutants were resistant to 13 U.S. phage isolates (4 prolate and 9 isometric). While Argentinian phage Stl-3 multiplied on U.S. culture isolate 59-1, low adsorption (38%) and insignificant burst size and latent period data were evident. Antisera prepared against U.S. phage D59-1 (prolate) and F4-1 (isometric) neutralized the lytic activities of all Argentinian prolate phage although the F4-1 antiserum was less effective. The data suggest homology especially between U.S. phage D59-1 and the Argentinian phage. PMID- 1911086 TI - Recovery of Listeria monocytogenes on selective agar media in a collaborative study using reference samples. AB - Sixteen laboratories compared counts of Listeria monocytogenes in reference samples using Blood agar, Palcam(y) agar and Oxford agar. Significant differences were found between laboratories. The mean counts on Blood agar were significantly higher than on Palcam(y) or Oxford agar. The mean counts on Palcamy agar were somewhat higher than on Oxford agar (only after 48 h incubation), but no significant difference was found. Addition of egg yolk to Palcam agar seems to be beneficial for the recovery of sublethally injured cells. Recovery of L. monocytogenes was higher after 48 h incubation for all media tested. PMID- 1911087 TI - Collaborative study of the International Office of Cocoa, Chocolate and Sugar Confectionery on Salmonella detection from cocoa and chocolate processing environmental samples. AB - A comparative collaborative study was performed in 13 laboratories to evaluate the use of motility enrichment on Modified Semisolid Rappaport-Vassiliadis medium for rapid Salmonella detection from food-processing environmental samples. Artificially contaminated chocolate scrapings and naturally contaminated cocoa bean dust samples were used in the study. Pre-enrichment was performed in buffered peptone water with added casein and malachite green oxalate. Motility enrichment was compared with a conventional cultural procedure using Rappaport Vassiliadis broth and selenite cystine broth as selective enrichment. The productivity of motility enrichment was 93.5% compared to a productivity of the cultural procedure of 92%. Statistical analysis showed that there was no significant difference between the two procedures. Modified Semisolid Rappaport Vassiliadis medium is a sensitive and simple diagnostic tool for the microbiological safety evaluation of food-processing environments. PMID- 1911088 TI - Effect of lactic cultures on Escherichia coli in ewes' milk stored at low temperatures. AB - The behaviour of Escherichia coli in pasteurized ewes' milk inoculated with different lactic starter cultures and incubated at temperatures in the range 4-16 degrees C for 96 h was investigated. Growth temperature of lactic starter cultures before inoculation had a significant effect on inhibition of E. coli. The growth temperature of lactic starter inoculum which resulted in the highest inhibitory activity was 24 degrees C. Size of lactic starter inoculum also significantly influenced growth of E. coli, with a higher inhibition for 1% inoculum than for 0.1% or 0.3% inocula. Single cultures of Lactococcus lactis showed a stronger inhibitory activity than single cultures of Leuconostoc cremoris or Leuconostoc dextranicum. A lactic starter culture comprising Lactococcus lactis, Leuconostoc cremoris and Leuconostoc dextranicum resulted in the strongest inhibition. Stimulation of E. coli by the lactic starter cultures was frequently recorded at 4 degrees C and 8 degrees C. However, none or a very limited growth of E. coli was seen at these temperatures. PMID- 1911089 TI - Survival of Yersinia enterocolitica and Escherichia coli in spring water. AB - Survival of pure and mixed cultures of Yersinia enterocolitica and Escherichia coli in sterile spring water stored at 4 degrees C was evaluated. Y. enterocolitica increased two or three logs during the first 3 weeks of incubation, and at the end of 64 weeks viable cells in numbers corresponding to the initial inoculum level were still detectable. However, after 1 week of incubation, the number of E. coli in water started to decrease and in 13 weeks time no E. coli was detected. More rapid decrease of E. coli was observed in mixed cultures. PMID- 1911091 TI - Magnesium protection against anthracycline toxicity in vitro. AB - The clinical usefulness of the antitumour agents daunomycin (DAU) and adriamycin (ADR) is limited by their secondary cardiotoxicity. The anthracycline compounds have a number of detrimental effects on the biochemical and morphological integrity of the cardiac cell which may be related to the accumulation of cellular calcium. Using a model of spontaneously beating, cultured neonatal rat cardiomyocytes, we examined the cardioprotective role of magnesium during 2 hours of exposure to 10, 25 or 50 micrograms/ml DAU. A significant preservation of myocyte membrane integrity and cellular morphology was observed with the addition of equimolar magnesium. Magnesium opposes the actions of calcium in a number of tissues and it may be this calcium antagonist action that makes magnesium effective in DAU toxicity. PMID- 1911090 TI - Incidence of Listeria monocytogenes in meat production environments of a South Island (New Zealand) mutton slaughterhouse. AB - The results of a survey conducted at a South Island, New Zealand, abattoir are presented. Two-hundred-and-eighteen samples taken from ovine carcasses and the environment were analysed. The traditional cold enrichment, i.e. 4 degrees C for up to 16 weeks, was used. No isolations of listeriae were made from freshly dressed carcasses or from surfaces with which meat makes contact. However, seven isolates of Listeria monocytogenes were obtained from cold rooms operating at 5 degrees C and which are used to store carcasses. Also, a single isolate of L. ivanovii was obtained from a mesh screen strainer of the waste water treatment plant located near the works. The study indicates that ovine carcasses can be prepared free of L. monocytogenes, that cold rooms may be a source of these microorganisms and it also reconfirms that listeriae can be found in soil and fodder of animal paddocks adjacent to the abattoir. PMID- 1911092 TI - Perinatal magnesium metabolism: personal data and challenges for the 1990s. AB - This review addresses recent developments in the field of perinatal magnesium (Mg) metabolism. After a brief review of perinatal Mg physiology, it critically addresses the issue of possible teratogenicity of Mg deficiency; maternal hypermagnesaemia and its effects on pregnancy, the fetus, and the newborn; the role of Mg in neonatal calcium homeostasis; and the possible relationship between Mg deficiency, apnoea of prematurity, and sudden infant death syndrome. PMID- 1911094 TI - Changes in serum, erythrocyte, and urinary magnesium after a single dose of cisplatin combination chemotherapy. AB - The changes in serum and erythrocyte Mg concentrations and in renal Mg excretion induced by a single dose of cisplatin (100 mg/mq body surface area) were investigated in 16 patients with lung cancer. Magnesuria increased significantly (P less than 0.001) the day after cisplatin administration, returned to basal levels in the following days, and increased again on the 7th day (P less than 0.05). Magnesaemia decreased gradually and after 7 was significantly lower than before treatment (P less than 0.05). Erythrocyte Mg decreased significantly on days 1 (P less than 0.05) and 2 (P less than 0.001) after cisplatin administration, began to increase on day 4, and recovered to pretreatment values on day 7. These results suggest that, besides the well known damage to tubular function with consequent increase in renal Mg wasting, cisplatin may also interfere with Mg metabolism at cellular and subcellular levels. The activity of the drug on nucleic acids and membrane transport systems, where Mg is abundant and exerts important stabilizing functions, could induce Mg mobilization and increased membrane permeability, with a consequent shift of Mg from cells into the blood stream. This would counterbalance the increase in magnesuria, and magnesaemia would decrease significantly only when intracellular Mg returns to pretreatment levels. PMID- 1911093 TI - Changes in plasma, erythrocyte, and urinary magnesium with prolonged swimming exercise. AB - Erythrocyte, plasma and urinary magnesium were observed in a group of 8 well trained swimmers and in a group of 10 untrained subjects before, 2 minutes after and 30 minutes after a swimming test. After effort, plasma Mg (pMg) decreased significantly in both groups. Erythrocyte and urinary Mg variations were not significant in this study. PMg decrease after effort was more important in the swimmers group than in the untrained group (12% versus 6% after 2 minutes; 21% versus 4% after 30 minutes). The observed fall in plasma Mg concentration after exercise cannot be explained by a shift into erythrocytes during exercise, since the Mg content of these blood cells did not suffer significant alterations. The possible causes of the observed phenomena are discussed. PMID- 1911095 TI - Toxic metals and human amniotic ion permeability. II. Ultrastructural study and relationship with magnesium. AB - Measurement of the ratio between the volume of the intercellular space (R1), the microvilli (R2), the podocytes (R3), and the nucleus (R4) versus the cell volume indicates the effects of lead (Pb), cadmium (Cd), arsenic (As), and mercury (Hg) on the ultrastructure of the human epithelial cells. R1 is decreased by all toxic metals except Pb. R2 is increased by Cd and As, and decreased by Pb. R3 is not affected. R4 is increased only by As. The addition of MgCl2 to the bathing medium antagonizes the effect of Cd on the intercellular space, of Pb on the microvilli, and of As on nucleus. On the other hand, Mg enhances the effects of Pb on R1 and those of Cd and As on R2. Mg may be either a competitive inhibitor or an activator of the effects of the toxic substances examined in relation to their storage sites. PMID- 1911096 TI - Tissue and blood magnesium levels in spontaneously hypertensive rats, at rest and in stressful conditions. AB - Magnesium (Mg) levels were measured by flame atomic absorption spectrophotometry in the blood (plasma, erythrocytes) and soft tissues (liver, brain, heart, aorta, kidneys, adrenals, spleen, thymus) of adult spontaneously hypertensive rats (SHR) and their normotensive controls, Wistar Kyoto (WKY). In experiment 1, Mg determinations were performed on eight animals of each strain at rest. Mg levels were lower in brain (P less than or equal to 0.05), kidneys (P less than or equal to 2.10(-4] and erythrocytes P less than or equal to 0.01) in SHR than in WKY rats. Tissue water content was the same in the two strains. These results suggest the occurrence of lower intracellular Mg levels in SHR than in WKY. In experiment 2, 15 SHR and 15 WKY were submitted either to acute (1 d) or subacute (22 d) stresses or reared in restful conditions. Acute stress induced important Mg shifts leading to a decreased difference between SHR and WKY in most tissues and to an increased and more significant difference (P less than or equal to 0.01) in spleen and plasma Mg levels. Subacute stress was milder and had little effect. It is concluded that the results of experiment 1 cannot be attributed to the greater sensitivity of SHR to laboratory manipulations. When compared with previously published data our results nevertheless suggest an association between stress sensitivity and genetic factors regulating Mg metabolism. PMID- 1911097 TI - Dietary fructose produces greater nephrocalcinosis in female than in male magnesium-deficient rats. AB - The synergistic interaction of fructose and magnesium (Mg) deficiency on kidney calcification was compared in male and female rats. Male and female weanling rats were divided into four dietary groups: fructose or starch, with or without Mg. Rats were fed their respective diets for 9 weeks, and 24 h urine was collected to measure urinary output, pH, Mg, calcium (Ca), and oxalic acid. Rats were fasted overnight. After decapitation, blood was collected immediately, and kidneys were removed to determine their Mg and Ca content. Dietary fructose significantly increased kidney Ca in female rats fed deficient or adequate Mg diet and in male rats fed Mg-deficient diet only; the greatest kidney calcification occurred in female rats fed Mg-deficient diet (P less than 0.0001). Even in starch groups female rats fed the Mg-deficient diet showed some kidney Ca accumulation. The synergistic interaction of fructose and magnesium deficiency on nephrocalcinosis was significantly greater in female than in male rats. Low urinary output, optimal pH 6.8 for calcium phosphate precipitation, hypercalcaemia, hypercalciuria, hypomagnesuria, and low ratio of urinary Mg to Ca may independently or multifactorially contribute to nephrocalcinosis. The possible mechanism of this interaction is discussed. PMID- 1911099 TI - Non-invasive in vivo localized 1H spectroscopy of human astrocytoma implanted in rat brain: regional differences followed in time. AB - Human astrocytoma cells were cultured and inoculated into the rat brain. From the pre-clinical to the terminal state, tumour growth was monitored by in vivo MR imaging and by localized water-suppressed 1H spectroscopy (0.12-0.15 cm3 volumes) and spectroscopic imaging (0.01 cm3 voxels) employing the ACE localization technique. The MR experiments were conducted completely non-invasively, leaving the scalp intact. Brain spectra were obtained, showing distinct resonances for more than five different brain metabolites; they were not contaminated with lipid signals because of the adequate localization. Tumour progression, monitored in a selected volume of interest, was reflected in the corresponding spectra by decreasing intensities for resonances of N-acetyl aspartate and (phospho)creatine and increasing intensities for resonances of choline compounds and lactate. From spectroscopic imaging experiments metabolic heterogeneity could be deduced within the tumorous region. At particular times during tumour development spectra were obtained greatly resembling localized 1H MR spectra obtained from patients with astrocytomas by the use of similar localization methods. This emphasizes the relevance of animal model study for the evaluation of MR spectroscopic investigations in human brain tumour diagnosis and therapy evaluation. PMID- 1911098 TI - 31P magnetic resonance spectroscopy is sensitive to tumor hypoxia: perfusion and oxygenation of rat 9L gliosarcoma after treatment with BCNU. AB - The mechanism behind the relative increase in high-energy phosphates observed by MRS in many tumors following chemotherapy is poorly understood. To test the hypothesis that this metabolic activation is associated with a decrease in tumor hypoxia, tumor blood flow and oxygenation were measured in tumors that were also analyzed by MRS. 31P MR spectra were acquired with a GE 2T CSI spectrometer from subcutaneous 9L tumors in rats 4 days following treatment with BCNU (10 mg/kg) and from age-matched sham-treated control tumors. BCNU-treated tumors (n = 13) underwent a significant improvement in bioenergetic state compared to control tumors (n = 14), showing a relative increase in high-energy phosphate (Pi/phosphocreatine) (p less than 0.01), and a relative decrease in Pi (Pi/alpha nucleoside biphosphate) (p less than 0.01). Gamma camera imaging of 133Xe washout, following injection of 133Xe in saline into control and treated 9L tumors 4 days after treatment, was used to measure tumor perfusion. Sham-treated control tumors (n = 21) were perfused at a rate of 35.4 (+/- 6.4 SE) mL/100 g/min, while BCNU-treated tumors (n = 20) were perfused at a rate of 55.1 (+/- 7.5 SE) mL/100 g/min (T = 1.96; p less than 0.05). The partial pressure of oxygen (pO2), measured with a polarographic electrode was found to be significantly higher in treated 9L than in sham-treated controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1911100 TI - 13C NMR spectroscopic analysis of phospholipid metabolism in adrenal chromaffin cells. AB - Phosphatidylcholine (PC) metabolism in bovine adrenal chromaffin cells has been studied in vivo with 100 MHz 13C NMR spectroscopy. The incorporation of 13[CH3]choline was examined in cells embedded in 1% agarose strands and perfused at 37 degrees C. The pattern of 13C NMR spectroscopy. The incorporation of [13CH3]choline incorporation into PC of suspension cultures of chromaffin cells. The chemical shifts of labelled carbons in [13CH3]choline before and after their incorporation into PC are identical (ca 56.4 ppm). Incorporated [13CH3]choline can be released from the cells by phospholipase D which reduces the cellular PC signal by greater than 85%, indicating that a major fraction of the labelled PC is on the external membrane surface. This application of NMR spectroscopy provides a basis for direct measurement of the in vivo metabolism of PC in functioning adrenal chromaffin cells. PMID- 1911101 TI - Time-dependent effects of anesthetic agents on 31P NMR high-energy phosphates in KHT and RIF-1 fibrosarcomas. AB - Previous studies have reported significant radiobiological and hemodynamic effects associated with sodium pentobarbital (PB) anesthetization. The present work contrasts the effects of PB with azaperone-ketamine (AZ) in RIF-1 and KHT tumors while animal body core temperature is maintained at 37 degrees C. The primary aims were to evaluate both agents in terms of: (i) duration of anesthetic; (ii) effect on absolute levels of 31P NMR phosphocreatine (PCr) + beta-nucleoside triphosphate (beta-NTP)/inorganic phosphate (Pi) ratios; and (iii) effect on temporal variability of PCr + beta-NTP/Pi ratios. In terms of overall duration, AZ was the clear preference. Although the maintenance of 37 degrees C core temperature significantly reduced overall durations for both anesthetics, AZ animals invariably remained immobile for a minimum of 80 min. For PB, durations were highly unpredictable. With AZ, mean PCr + beta-NTP/Pi ratios were constant over the entire 80 min period for both lines. With PB, PCr + beta NTP/Pi ratios were lower in relation to AZ for KHT at select timepoints, but highly variable among RIF-1 tumours. Since ratios under PB varied substantially with time for RIF-1 lines, measurements taken with PB are clearly not representative of the control state. Furthermore, in light of the consistent and reproducible results obtained with AZ, this anesthetic is considered a marked improvement over PB for animal studies of this nature. PMID- 1911102 TI - Proton nuclear magnetic resonance spectroscopy measurements of methylene and methyl line widths in plasma: significant variations with extent of breast cancer, duration of pregnancy and aging. AB - The composite methylene (chemical shift range 1.2-1.4 ppm) and methyl (0.8-0.9 ppm) resonances of the 1H NMR spectrum were analyzed in plasma samples from breast tumor patients, pregnant women, and healthy subjects. Using a 500 MHz NMR instrument operating at 25 degrees C, the peaks were analyzed for line width at half height and then averaged. A statistically significant difference (p less than 0.001) was found between the average (mean +/- SD) line width in the plasma samples from the 30 patients with metastatic breast cancer (34.1 +/- 5.0 Hz) and the controls matched for age and sex (38.7 +/- 4.4 Hz). In the 16 patients with localized breast cancer and the 16 with regional spread, the average line width was not different from that of matched controls. In 21 patients with benign tumor in the breast, the average line width was not different from that of matched controls. A difference in the average line width was found between 31 pregnant women in the third trimester (32.5 +/- 3.4 Hz) and their controls matched for age and sex (42.7 +/- 4.6 Hz) (p less than 0.001). The average line width was lower in the late (31.5 +/- 3.3) than in the early (34.5 +/- 2.5 Hz) part of the third trimester (p = 0.022). In 54 healthy male and 130 healthy female controls, line widths declined gradually with increasing age by decades, except in the fifth decade for the men and the sixth decade for the women.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1911103 TI - Non-invasive 1H NMR spectroscopy of the rat brain in vivo using a short echo time STEAM localization sequence. AB - Fully localized proton NMR spectra were obtained from the brains of normal anaesthetized rats in vivo using stimulated echo (STEAM) spectroscopy sequences. Investigations were carried out at 2.35 T using a 40 cm bore magnet equipped with an actively shielded gradient system. Localized shimming resulted in water proton linewidths of 6.5-7.8 Hz permitting excellent water suppression. Thus, high quality proton NMR spectra (TE = 20 ms) were acquired within measuring times of 1.5-6.4 min from 64 to 125 microL volumes-of-interest. The spectra show metabolite resonances due to N-acetyl aspartate, glutamate, creatine and phosphocreatine, cholines, taurine and inositols. The assignments of strongly spin-coupled resonances were confirmed by comparison with spectra from model solutions obtained under identical experimental conditions to those used in vivo. T1 relaxation times as well as relative metabolite concentrations were evaluated from spectra obtained for repetition times ranging from 900 to 6000 ms. Sequential acquisitions of 1.5 min spectra before, during and after killing the animals exhibited a rapid accumulation of lactate, but did not reveal significant changes in other metabolite levels for several hours post mortem. PMID- 1911104 TI - Localized steady-state oxygen measurements from the preretinal space of the rabbit eye using 19F NMR. PMID- 1911105 TI - Sodium dodecyl sulphate polyacrylamide gel electrophoresis patterns of proteinuria in various renal diseases of childhood. AB - This study examined the potential of an automated electrophoretic system (PHASTSYSTEM, Pharmacia. Uppsala, Sweden) to distinguish patterns of proteinuria in children with various renal diseases. It proved possible to produce ready-to read sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS PAGE) separation of 1 microliter of unconcentrated urine in 2 h. Glomerular, tubular and mixed patterns of proteinuria were identified. Steroid-responsive nephrotic syndrome (SRNS) was readily identified by strong bands of albumin and transferrin during relapses. In contrast, steroid-resistant nephrotic syndrome was associated with two additional bands of haptoglobin and IgG. Albumin dimers (Mr 120 kDa) were found in the active phase of the disease in the urine of 90% of children with SRNS. Patterns of tubular proteinuria were found in children with proximal renal tubular abnormalities. The presence of mixed patterns of glomerular and tubular proteinuria strongly suggest renal insufficiency. SDS PAGE electrophoresis can readily be applied in clinical practice. It may prove helpful in the diagnosis and management of children with renal diseases enabling correlation to be made between proteinuria, renal pathology and prognosis. PMID- 1911106 TI - Differentiation of proteinurias with electrophoresis. PMID- 1911107 TI - A comparison of two common clinical methods with high-pressure liquid chromatography for the measurement of creatinine concentrations in neonates. AB - The accurate measurement of low serum creatinine levels is necessary for estimating clinically useful creatinine clearances in the pediatric population. This study compares two routine clinical methods: the kinetic Jaffe with the newer Kodak enzymatic method against our reference method, high-pressure liquid chromatography, for the measurement of serum and urine creatinine levels in neonates. One hundred and twenty-five serum and 59 urine creatinines and 56 absolute creatinine clearances were measured in neonates ranging from 23 to 46 weeks (mean 32 weeks) post-conceptional age and weighing 480-4398 g (mean 1650 g). Urine creatinine levels, and serum creatinine levels greater than 0.8 mg/dl were equivalent for both clinical methods. However, the enzymatic method was much more accurate (P less than 0.001) than the kinetic Jaffe method for serum creatinine measurements of less than or equal to 0.8 mg/dl. We conclude that the enzymatic methodology is a better clinical choice for the accurate measurement of serum creatinine levels when using these values for the determination of neonatal renal function. PMID- 1911108 TI - Course and long-term outcome of idiopathic IgA nephropathy in children. AB - The long-term outcome of idiopathic IgA nephropathy (IgAN) in children was investigated with regard to clinical course and biopsy changes. All patients with biopsy-verified IgAN (diagnosed by kidney biopsy 1970-1985) at three children's clinics in Sweden were included in the study. Thirty-four (10 females, 24 males), out of a total of 72 patients, had a follow-up period of 8 years or more (10.7 +/ 1.9 years, range 8-14). After this duration of follow-up, urine abnormalities were found in 47% (group A), proteinuria in 35%, hypertension in 9%, and decreased glomerular filtration rate (GFR) in 3% of patients. However, 53% had no clinical signs of disease (group B). GFR depression at the time of clinical presentation of IgAN was more common in group A than in group B (P = 0.017). At the first renal biopsy, which was performed after the same duration of IgAN in both groups, focal segmental glomerular changes were more often found in group A (P = 0.017), while diffuse proliferative changes were more common in group B (P = 0.031). The course of the IgAN was thus often very protracted, with some children developing hypertension as well as decreased renal function. However, after a period of 8 years or more of follow-up half of the patients did not show any clinical signs of the disease, which may indicate low disease activity or, possibly, recovery. PMID- 1911109 TI - Further evidence of lipid peroxidation in post-enteropathic haemolytic-uraemic syndrome. AB - Lipid peroxidation may play a role in the pathogenesis of the haemolytic-uraemic syndrome (HUS). Thirteen children with the post-enteropathic form of HUS were studied using conjugated diene lipids as markers of in vivo lipid peroxidation. Levels of total conjugated diene lipids and 9,11-linoleic acid, the principal conjugated diene in human plasma, were greater in the acute phase of this disorder than in controls. The ratio of plasma vitamin E to lipid was lower than that in children with other renal diseases, and the expected positive correlation between vitamin E and lipids did not hold for HUS patients. These data provide further evidence of lipid peroxidation in HUS and a disturbance in the metabolism of the principal lipid-bound anti-oxidant vitamin E. PMID- 1911110 TI - Are there advantages to bicarbonate dialysis as a standard procedure for chronic hemodialysis in children? PMID- 1911111 TI - Racial differences in the incidence and renal outcome of idiopathic focal segmental glomerulosclerosis in children. AB - The North American Pediatric Registry reports that from 1987 to 1989 blacks and Hispanic children accounted for 23% of all renal transplants performed but 38% of those performed for focal segmental glomerulosclerosis (FSGS). From these data, we infer that blacks and Hispanics form a disproportionate number of FSGS patients who progress to end-stage renal disease (ESRD) compared with white children. To explore this hypothesis we assessed our single-center experience of FSGS comparing black and Hispanic with white children. Of 177 black and Hispanic children followed in our clinic for idiopathic nephrotic syndrome (NS) between 1974 and 1989, 57 were diagnosed as having FSGS (group I). The mean age at onset of NS of these group I patients was 7.3 +/- 4.6 years and the mean duration of follow-up was 8.25 +/- 4.3 years. During the same period, 13 of 65 white patients (group II) with idiopathic NS were found to have FSGS. Their mean age (7.8 +/- 4.8 years) and duration of follow-up (8.8 +/- 4.8 years) were similar. Therapeutic modalities in the two groups were also similar. Of group I patients, 78% (42/54) reached ESRD compared with 33% (4/12) of group II patients (P less than 0.01). Life table analysis showed that 50% of black and Hispanic children will reach ESRD within 3 years of FSGS.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1911112 TI - A practical approach to evaluating urinary tract infection in children. AB - After a first urinary tract infection (UTI), all children require an evaluation with imaging studies to screen the urinary tract for anatomic abnormalities and for reflux. Ultrasonography and voiding cystography readily accomplish this and are recommended, knowing that such a recommendation is controversial. While the likelihood for reflux-induced renal damage is age related, the presence of reflux in any child with infection is clinically important for management. Abnormal screening results or recurrence of infection warrant further radiographic testing. However, imaging studies are necessary but do not constitute sufficient evaluation for UTI because the etiology of infection is only rarely identified with these tests. Sorely neglected in most recommended protocols for evaluating urinary infection is an investigation for micturitional disturbances which may be responsible for the infections. Treatment of these conditions may actually prevent recurrence of infection. Controversy surrounding the proper imaging evaluation for UTI appears to be mis-directed. Instead of arguing about which imaging study should be performed or which child with a first UTI should have a cystogram, our patients might be better served if we wondered why traditional protocols for evaluating UTI deal only with imaging studies. PMID- 1911115 TI - Molecular basis of transplant rejection and acceptance. AB - The field of kidney transplantation is advancing so rapidly that it is difficult to keep up with the various therapeutic protocols, let alone our current understanding of transplantation immunobiology. This basic science review summarizes our current understanding of aspects of the cellular and molecular basis of renal transplant rejection and then details studies from the author's laboratory designed to specifically interrupt transplant rejection. The interaction of HLA with T cell receptors and the cascade of events following T cell activation are highlighted. PMID- 1911116 TI - Paediatric nephrology on the threshold of European integration. AB - The European Society for Paediatric Nephrology (ESPN) was founded 25 years ago. The progress of paediatric nephrology in Europe since then has been considerable, but we now face a number of problems. The care of the child with kidney disease is often expensive and more needs to be done to examine the cost effectiveness of the management of the child with kidney disease. International co-operation can also foster clinical research to determine the effectiveness of treatment through the institution of controlled trials and outcome studies. Particular problems are posed by the need to integrate the countries of Eastern Europe that have changed from command to market economies over the last year. In many instances there is no shortage of doctors, nurses and hospital beds but there is a need to change administrative and academic structures and to introduce appropriate technology. It is suggested that this may be assisted by twinning units. The integration of Europe requires that the role of the paediatric nephrologist in different countries needs to be examined, and appropriate training to fulfil these responsibilities needs to be agreed. Different countries obviously have different ways of organising and providing services for children with kidney disease. Kidney failure is rare in childhood and there are economic and academic advantages from close collaboration, both with adult nephrology services and with other paediatric specialities. Where it is intended to integrate children's hospitals into large multidisciplinary university hospitals for economic reasons, it is nonetheless necessary to make sure that the requirements of children are properly recognised and the requirements of the European Charter for children in hospital are met.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1911113 TI - Pathogenesis of the essential hypertensions. AB - The pathogenesis of essential hypertension (EH) is reviewed with a special focus on the development phase or the pre-hypertensive period. Three animal models are presented: the spontaneously hypertensive rat, the Dahl's salt-sensitive rat, and the Milan hypertensive rat. Some of the findings in animal models have inspired new fields and technical approaches for studying EH in man. From the original idea of Page, a new mosaic of various etiological parameters serves as a basis for reviewing the multiple facets of EH in man. One must conclude that EH is heterogeneous disease and most likely every single hypertensive patient belongs to a subgroup of the whole population of hypertensives. PMID- 1911114 TI - Recurrent primary disease and de novo nephritis following renal transplantation. AB - Recurrent or de novo diseases account for only 5% of graft failure in children, but have much to teach us about mechanisms. In children, almost the only metabolic disease with recurrence is type I hyperoxaluria, in which the poor long term results of isolated renal transplantation make combined liver and renal transplantation, or even prophylactic liver transplantation before renal failure the preferable alternatives. While many forms of nephritis may show histological recurrence in allografts, it is notable that in many patients this is accompanied by no clinical manifestations or only mild disease: this is particularly so in mesangiocapillary glomerulonephritis (MCGN) type II. IgA-associated nephropathy and Henoch-Schonlein purpura. However focal segmental glomerulosclerosis and MCGN type I recur with sufficient frequency and severity to deter the use of living donors unless there is no alternative. The same is true of haemolytic-uraemic syndromes. As many as 10% of paediatric grafts may show de novo membranous nephropathy, but in the majority this is mild or not clinically evident. In contrast, the rare anti-glomerular basement membrane nephritis affecting some patients with Alport's syndrome usually results in graft failure, but occurs in only a minority of recipients with the syndrome. For all types of disease in allografts, risk factors for recurrence are poorly worked out, and attempts at treatment generally ineffective. PMID- 1911117 TI - Clinical quiz. Congenital nephrotic syndrome, microcephaly, brain malformations and diaphragmatic abnormality associated with histological features of diffuse mesangial sclerosis. PMID- 1911118 TI - Vomiting and chronic renal failure. PMID- 1911120 TI - Analysing curves using kernel estimators. AB - In this paper a novel statistical method for curve fitting is described and applied to growth data for illustration. This technique, called kernel estimation, is non-parametric and belongs to the class of smoothing methods. Therefore, it does not need an a priori functional model where individual parameters are determined from the data. Functional models can only reflect features which have been incorporated into the model. Recent progress in selecting the degree of smoothing from the data makes the new method more easy to use and more objective. It applies to the curve itself or to its derivatives. PMID- 1911119 TI - Renal growth in infancy and childhood--experimental studies of regulatory mechanisms. AB - During the peri- and early postnatal period, nephrogenesis is completed and kidney growth is accomplished both by cellular proliferation and enlargement. The number of nephrons in a given species is predetermined, whereas cellular growth can be influenced by environmental factors in an age-dependent manner. Unilateral nephrectomy or a high-protein diet stimulates renal growth more in the young than in the adult. Conversely, pyelonephritis inhibits renal growth in infancy but not in adulthood. The relative importance of hyperplasia and hypertrophy for renal growth also changes with renal maturation. The mechanisms behind these developmental changes in regulation of renal growth are largely unknown, but age dependent changes in the expression of several proto-oncogene products have been demonstrated. These include growth factor receptors as well as components of the intracellular system that transfers the signal from an activated growth factor receptor to the cell nucleus. Studies on rat proximal tubule cells in primary culture might be of great value in expanding our knowledge of growth regulation in the developing kidney. Such studies have already shown that under identical environmental conditions the basal proliferative rate is age dependent, that the proliferative response to growth stimulation changes postnatally, and that this is associated with changes of both the response of the Na+/H(+)-exchanger and the expression of the c-fos proto-oncogene. PMID- 1911121 TI - Regulation of cartilage growth by growth hormone and insulin-like growth factor I. AB - A number of studies have shown that growth hormone (GH) and insulin-like growth factor-I (IGF-I) have important regulatory roles for skeletal growth. However, it has been a matter of controversy whether GH acts directly on cells in the growth plate or if the growth-promoting effects of GH are mediated by liver-derived (endocrine-acting) IGF-I. With the recognition that GH regulates the production of IGF-I in multiple extra-hepatic tissues, autocrine and paracrine functions of IGF-I have been suggested as important components of GH action. This review focuses on recent developments in our understanding of the cellular mechanisms by which GH promotes longitudinal bone growth and the inter-relationship between GH and IGF-I in the growth plate. PMID- 1911122 TI - How safe is the treatment of uraemic children with recombinant human growth hormone? AB - Exogenous growth hormone (GH) treatment for growth failure in uraemic children is effective over a period of up to 3 years. The safety of this new treatment modality is remarkably high, at least for this short period of time. Despite a reduced renal metabolic clearance rate of GH in uraemia, exogenous GH does not accumulate in the serum. In a dose range of 28 units/m2 per week, GH does not impair glucose tolerance but increases serum insulin levels, indicating that euglycaemia is maintained at the expense of increased insulin secretion. No alterations of lipid metabolism, mineral metabolism, pituitary-thyroid axis and blood pressure were observed. The GH-induced glomerular hyperfiltration in healthy subjects seems to be obliterated in chronic renal failure. Accordingly, no accelerated progression of renal disease was observed under GH treatment. However, potential side effects during long-term treatment, especially regarding carbohydrate metabolism and malignancy in children under immunosuppression, are not yet excluded. PMID- 1911123 TI - The application of knemometry in renal disease: preliminary observations. AB - Short-term lower leg length was measured longitudinally using a high-precision device called a knemometer in 11 children with chronic renal failure and 12 normal children. The method has a high accuracy (mean standard error 0.13 mm) and may prove useful for prediction of long-term total body growth. Its application in renal patients undergoing corticosteroid, growth hormone (GH) and erythropoietin (EPO) therapy is documented. GH was shown to improve lower leg growth in an adolescent who already had passed the maximum of his pubertal spurt. EPO treatment produced no consistent increase of short-term growth. PMID- 1911124 TI - Growth after renal transplantation: an update. AB - Several factors influencing post-transplant growth were analysed in a total of 163 children receiving transplants at the Medical School Hannover. Statural height at the time of transplantation depended on the length of the pre transplant period of chronic renal failure, and was more retarded in children with congenital renal diseases than in those with acquired diseases. The retardation of bone age correlated significantly with the degree of growth retardation. The immunosuppressive regimen of cyclosporine A (CyA) and low-dose prednisolone was followed by significantly better growth rates than azathioprine (Aza) plus high-dose prednisolone. In 22 prepubertal children receiving CyA, poor graft function with a glomerular filtration rate below 40 ml/min per 1.73 m2 inhibited catch-up growth. The final height of 20 grown-up transplant recipients was found to be in the lower range of normal. A comparison of conventional and CyA treatment showed that adult height in the CyA group was higher than in the Aza group due to a significantly higher growth velocity. PMID- 1911125 TI - Recombinant human growth hormone treatment of children with chronic renal failure: long-term (1- to 3-year) outcome. AB - Treatment of nine boys, aged 2.8-16.3 years, with growth retardation consequent to chronic renal failure (CRF), with recombinant human growth hormone (rhGH) for 12-36 months demonstrated a significant improvement in growth velocity at each 12 month interval compared with that achieved the year prior to treatment. Despite the acceleration in growth velocity the bone age did not increase more than the increase in chronological age during the period of treatment. The mean calculated creatinine clearance did not decrease significantly during the 36 months of treatment; however, two patients required institution of dialysis at 18 and 30 months following the initiation of rhGH treatment. There was no exacerbation of the glucose intolerance of uremia following rhGH treatment. Currently, six of seven patients who have been treated for more than 24 months have achieved sufficient acceleration of growth velocity to attain a standard deviation score that was more positive than -2.00, and are above the 5th per centile for chronological age on the growth curve. These data indicate that rhGH treatment of growth-retarded children with CRF results in accelerated growth velocity during the 2nd and 3rd years of treatment, and demonstrate the potential for such children to achieve normal stature for chronological age despite the continued presence of renal failure. PMID- 1911127 TI - Contribution of experimental studies on the nutritional management of children with chronic renal failure. AB - A few of the many reports of experimental chronic renal failure have been summarized. Anorexia and food selection have been studied in experimental uremia and the findings are comparable with those observed in uraemic children. The optimal dietary protein content for growth is close to the minimal requirement for "optimal" growth. Protein excess leads to growth retardation and renal deterioration in uraemic rats, at least with the commonly used dry diets. The increased water requirement may be more critical for growth than the blood urea level or acidosis, although this requires further investigation. Reduction of the dietary protein by 50% and supplementation with essential amino acids (EAA) results in growth similar to that of the 100% protein diet. There is no growth improvement despite low blood urea levels, but the renal parenchymal is preserved. Supplementation with nitrogen-free analogues is more frequently associated with defective growth; the optimal mixture remains to be defined, and to date, when nutrition is identical, nitrogen-free analogues offer no benefit for renal preservation compared with EAA. Sucrose-rich diets have adverse effects on uraemia. These effects are associated with fructose intolerance and with reduced energy storage in the liver. The precise metabolic alteration remains to be defined. PMID- 1911126 TI - Ineffectiveness of dietary protein augmentation in the management of the nephrotic syndrome. AB - The nephrotic syndrome is a consequence of altered permselectivity of the glomerular basement membrane resulting in urinary losses of albumin and other serum proteins. Although dietary protein augmentation increases albumin synthesis, it has not been shown to increase serum albumin or muscle protein. Dietary protein was increased from 8.5% to 21% in pair-fed rats with Heymann nephritis and resulted in an increase both in albumin synthesis and urinary albumin excretion, but not in serum albumin concentration or in total albumin pools. The increase in dietary protein was 8 times greater than the resulting increase in urinary protein excretion, but nearly all of the additional ingested protein was catabolized to urea and excreted in the urine rather than used to augment growth. Dietary supplementation with protein has no obvious beneficial effect on nutritional status of nephrotic rats. PMID- 1911128 TI - Effect of low-protein diet on renal function: are there definite conclusions from adult studies? AB - Low-protein diets have been used for roughly a century in order to alleviate uraemic symptoms and to delay progression of chronic renal failure (CRF). Currently a number of different low-protein diets are used, supplying either 0.6 g protein/kg body weight or 0.3-0.4 g supplemented with amino-acids or keto acids. Single centre trials have attempted to demonstrate the efficacy of these diets in slowing down the progression of CRF. The results from these trials are, however, sometimes inconclusive, showing either a high efficiency of the low protein diet or no efficiency at all. Conclusive data from multicentre trials, however, are not yet available. A crucial point in analysing the efficacy of low protein diets is the degree of compliance with the protein restriction. Today, the data available indicate that sometimes only a poor degree of compliance is achieved both in single and in multicentre trials. PMID- 1911129 TI - Low-protein diet in children with chronic renal failure--1-year results. European Study Group for Nutritional Treatment of Chronic Renal Failure in Childhood. AB - In 1988 the European Study for Nutritional Treatment of Children with Chronic Renal Failure started its multicentre randomized trial to investigate the influence of protein intake on the progression of renal failure. A total of 284 children had been registered. Of these 221 were accepted for the study. The data from 105 patients after 1 year of study are available for preliminary analysis. Fifty children were randomized for the diet group and 55 for the control group. Both groups were comparable concerning age, glomuerlar filtration rate (GFR) and height standard deviation score for chronological age at the start of the study period and the distribution of primary renal diseases and sex. Limits for protein and energy intake were set according to the safe levels and recommendations given by the World Health Organization. The compliance with dietary prescriptions as calculated from dietary diaries was good. A low-protein diet did not do any harm to the children with respect to length gain and weight gain. The progression of renal failure was minimal in the diet group (mean loss of GFR 3.6 ml/min per 1.73 m2 per year) as well as in the control group (2.3 ml/min per 1.73 m2 per year). The differences between the diet group and the control group were statistically not significant when either all patients or only subgroups of various primary renal diseases were analysed. When only patients with a good compliance were considered (documented by dietary diaries or by urea nitrogen excretion) the same results were obtained. In summary, reduction of protein intake was accepted by the majority of patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1911130 TI - Influence of growth hormone and insulin-like growth factor-I on kidney function and kidney growth. AB - Decreased glomerular filtration rate (GFR) in hypopituitarism and increased GFR in acromegaly suggest that growth hormone (GH) has a substantial effect on renal haemodynamics. Extractive and recombinant human (rh) GH in healthy volunteers increased effective renal plasma flow (ERPF) and GFR by 10% and 15% respectively. Renal response to GH was delayed and occurred at the same time as an increase in plasma insulin-like growth factor (IGF)-I values, whereas infusion of rhIGF-I promptly increased GFR and ERPF, indicating that the haemodynamic response of the kidney to GH is mediated by IGF-I. In chronic renal failure (CRF), the acute effect of GH on GFR is obliterated. This might protect the diseased kidney against the undesired consequences of hyperfiltration. Indeed, rhGH treatment for 1 year in children with CRF did not lead to an accelerated decline in GFR compared with the year before treatment. GH and IGF-I also affect renal growth. Exposure to excessive GH in transgenic mice causes renomegaly and progressive glomerular sclerosis. In acromegalic humans, increased renal size and weight and increased glomerular diameter are well known, whereas renal failure is not a long term hazard. At least in normal and hypophysectomized rats treated with doses comparable with the therapeutic regimens used in stunted children, rhGH increased renal weight but in proportion to the increase in body weight indicating an isometric effect of GH on renal growth. From these data, major renal long-term side effects of rhGH treatment in children with CRF appear unlikely. PMID- 1911132 TI - Analyzing pulsatile endocrine data in patients with chronic renal failure: a brief review of deconvolution techniques. AB - Deconvolution analysis provides an important new technique to evaluate underlying hormone secretory rates quantitatively based upon serially measured plasma hormone concentrations with or without prior knowledge of the half-time of hormone disappearance from the blood. Information about endocrine gland secretion is particularly important in chronic renal failure, wherein the decreased metabolic clearance rates of various hormones would otherwise confound the interpretation of plasma hormone concentrations. Here we review two particularly useful techniques of deconvolution, one of which is a waveform-defined algorithm and the other waveform independent. The first method can be used to estimate both hormone half-life and secretory rates in vivo. The second methodology allows calculation of in vivo hormone secretion rates without assuming any special form for the secretion event, but requires a priori knowledge of hormone half-life. We illustrate examples of these two deconvolution approaches, and discuss why the interpretations of hormone concentration measurements in earlier studies (where deconvolution methods were not employed) must be viewed with caution. Based on such considerations, additional investigations of in vivo hormone secretory pathophysiology will be required in children and adults with chronic renal failure. PMID- 1911131 TI - Accelerated growth and visceral lesions in transgenic mice expressing foreign genes of the growth hormone family: an overview. AB - Effects of growth hormone (GH) overproduction were studied in transgenic mice expressing murine metallothionein I-GH fusion genes. The most obvious consequence was the acceleration of growth, which led to substantial increases in body weight of up to more than twice that seen in controls. Growth of the internal organs was stimulated, with hepatomegaly and nephromegaly as the most prominent features. GH transgene expression was also reflected in increased skeletal growth which affected various bones to different extents. The mean life-span of human GH transgenic mice with serum levels of hGH ranging from 3 x 10(3) to 9 x 10(5) ng/ml was drastically reduced at 160 days in both sexes. Severe renal lesions were the primary cause of the decrease in life expectancy and were characterized by marked nephron atrophy, obsolescence of numerous glomeruli, and a massive cystic dilation of the tubules. Initial changes involved the glomeruli, which showed significant enlargement and sclerotic lesions. The liver exhibited a pronounced hepatocellularmegaly and progressive degenerative as well as hyperplastic changes. One-third of the hGH transgenic animals displayed myocardial fibrosis. Hepatocellular carcinoma was found in bovine GH transgenic mice older than 12 months. Our observations are compared with results of other investigators. PMID- 1911133 TI - Effect of growth hormone on kidney growth and glomerular structure. AB - The effect of growth hormones (GH) on renal growth was measured in growing uremic rats using a five-sixths nephrectomy model and GH, 5 mg/kg per day. At the end of 8 weeks, somatic size was significantly smaller in the untreated uremic rats. The uremic rats given GH were the same size as the non-uremic control animals. Organ size (heart, liver and kidney) differed in that only untreated uremic animals had a significantly smaller kidney weight. Despite a five-sixths nephrectomy, the uremic animals receiving GH had kidneys the same size as sham-operated control animals. Renal function was not changed by GH therapy in either control or uremic animals. DNA content expressed as milligrams per kilogram kidney tissue was low only in the untreated uremic rats. Glomerular volume and proximal tubular area were elevated in both groups of uremic animals but were elevated to a significantly greater degree in those receiving GH. GH given in large doses to growing animals appears to induce both somatic and renal growth. PMID- 1911134 TI - Renal pathology in rats bearing tumour-secreting growth hormone. AB - The effects of growth hormone (GH) on renal structure and function were investigated in rats aged 10-16 weeks bearing a tumour secreting GH. Body weight gain, food intake, urine volume, and urinary excretion of creatinine and urea nitrogen were significantly greater in tumour-bearing rats than in controls. The tumour-bearing rats presented progressive proteinuria, hyperproteinaemia, and hyperlipidaemia. Creatinine clearance was significantly higher in experimental animals during the early experimental stage, but decreased as the glomerular lesions progressed, associated with a rise in serum creatinine levels. The glomeruli became progressively enlarged with degenerative changes of the visceral epithelial cells and capsular adhesions. In advanced stages proteinaceous material invaded the subcapsular space and the capillary lumen collapsed finally leading to glomerulosclerosis. Except for the presence of proteinaceous material and damaged epithelial cells the glomerular lesions resemble those observed experimentally after reduction of renal mass, and in diabetes mellitus. We speculate that the pathological features described are due to effects of persistently high levels of circulating GH on the glomerular cells. PMID- 1911135 TI - Plasma growth hormone-binding activity is low in uraemic children. AB - Plasma growth hormone-binding protein (GH-BP) activity was evaluated in two groups of prepubertal children with chronic renal failure (CRF) who had been treated with recombinant human GH (rhGH). Group 1 consisted of eight children (mean chronological age 10.8 years) with advanced renal failure; group 2 consisted of nine children (mean chronological age 6 years) presenting with end stage renal disease, who were on dialysis. Before treatment the specific binding of (125I)hGH to high-affinity GH-BP was low in the two groups (group 1, 17.3 +/- 1.6% of radioactivity; group 2, 14.2 +/- 1.4%) compared with the mean value obtained in normal prepubertal children (24.8 +/- 1.7%). No significant changes in GH-BP activity were found during the 1st year of GH therapy, although growth velocity and plasma levels of insulin-like growth factor-I increased significantly in both groups. The low GH-binding activity found in children with CRF supports the state of GH resistance. The reason for the absence of a GH-BP response to GH therapy has to be clarified. PMID- 1911136 TI - Recombinant human growth hormone overcomes the growth-suppressive effect of methylprednisolone in uraemic rats. AB - Paediatric renal allograft recipients frequently manifest growth retardation because of suboptimal graft function and/or concomitant corticosteroid treatment. To determine if the growth-suppressive effects of methylprednisolone (MP) could be counterbalanced by concomitant treatment with recombinant human growth hormone (rhGH) under conditions of normal and reduced renal function, the following animal model was set up. Female uraemic Sprague-Dawley rats (140 g) together with pair-fed and ad libitum-fed control animals were treated with 6 mg/kg per day MP with or without 10 IU/kg per day rhGH. MP suppressed linear growth and weight gain by 43% and 63%, respectively in ad libitum-fed normal control animals; the suppression was more pronounced in uraemic animals (57% and 107%, respectively). The suppressive effects were independent of food intake. The food conversion ratio (weight gain/food intake) was diminished to one-third in control and to more than one-tenth in uraemic animals. Concomitant treatment with rhGH completely reversed the suppression of length gain and weight gain (total body and muscle) and normalized the food conversion ratio. We concluded that rhGH can completely reverse the catabolic effects of corticosteroids under conditions of normal or reduced renal function. The data provide a reasonable rationale for prospective controlled studies on the use of rhGH treatment in paediatric kidney transplant recipients with growth failure. PMID- 1911137 TI - The influence of steroid therapy and recombinant human erythropoietin on the growth of children with renal disease. AB - Long-term steroid therapy has a depressant effect on hypothalamo-pituitary pulsatile secretion of growth hormone (GH), and this results in an attenuated pubertal growth spurt. Oxandrolone and recombinant human GH improve growth rates in children taking long-term steroid therapy for renal disease, but there are potential side effects. Treatment with recombinant human erythropoietin improved the growth of three prepubertal, but not three pubertal haemodialysis patients. PMID- 1911138 TI - Biological activity of luteinizing hormone in uraemic children: spontaneous nocturnal secretion and changes after administration of exogenous pulsatile luteinizing hormone-releasing hormone--preliminary observations. AB - Normal pubertal progression is associated with quantitative and qualitative changes in gonadotrophin release. Uraemic children show a delayed or disturbed puberty. We have therefore examined nocturnal gonadotrophin and sex steroid secretion in seven males and three females [age 11-15 years, pubertal stage (PS) 1-3] with chronic renal failure on conservative treatment. In addition to immunoreactive luteinizing hormone (i-LH) we have measured the biological activity of LH (b-LH). Nine children aged 12-17 years with PS 1-3 and normal renal function served as a control group. In two uraemic children, i-LH, b-LH, follicle stimulating hormone and sex steroids were evaluated before and 7 days after pulsatile LH-releasing hormone (LHRH) administration (150 ng/kg body weight subcutaneously every 120 min). Mean i-LH levels were higher in uraemic children than in controls. An increase in i-LH during sleep was found in all controls and in eight of ten uraemic subjects. Mean b-LH levels were lower during sleep and the b/i LH ratio was reduced in uraemic children with PS 2-3 whether asleep or awake compared with controls. Pulsatile administration of LHRH provoked a rise of i-LH and b-LH levels with an increased b/i LH ratio, suggesting an intact pituitary responsiveness. These preliminary data indicate that the gonadotrophin control of LH is abnormal in uraemic children, and that biopotency of LH secretion might be improved after short-term pulsatile LHRH administration. PMID- 1911139 TI - Pulsatile immunoreactive and bioactive luteinizing hormone secretion in adolescents with chronic renal failure. The Cooperative Study Group on Pubertal Development in Chronic Renal Failure (CSPCRF). AB - Delayed or arrested pubertal development is common in children with chronic renal failure (CRF). Normal puberty is initiated by the onset of episodic nocturnal secretion of luteinizing hormone (LH) containing an increasing proportion of bioactive hormone. To test the functional integrity of the hypothalamo-pituitary axis in CRF we measured immunoreactive (i-LH) and bioactive (bio-LH) plasma LH concentrations at 15-min intervals from 2000 to 0700 hours in 65 pubertal patients aged 10-23 years [46 boys/19 girls; 20 on conservative treatment (CT), 13 on dialysis (D), 32 with transplants (TP)]. i-LH was determined by radio immunoassay and bio-LH by a mouse Leydig cell assay. Peak detection was performed by the cluster analysis computer programme. The mean (+/- SD) number of i-LH (in both sexes) and bio-LH pulses (in boys) per profile, and the mean peak area of i LH (in both sexes) and bio-LH (in girls) were higher in TP than in CT or D patients. The ratio of bio-LH to i-LH increased during puberty in CT (G1 vs G4/5, 0.3 +/- 0.5 vs 1.8 +/- 0.,4) and TP (0.6 +/- 0.7 vs 1.8 +/- 0.7) but remained low in male D patients (0.4 +/- 0.7 vs 1.1 +/- 0.8). The ratios were subnormal, however, even in mature TP patients compared with healthy adults. The bio-LH/i-LH ratio and the bio-LH peak area best predicted integrated nocturnal testosterone concentrations in TP but not in uraemic male patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1911140 TI - Asymptomatic isolated microhaematuria: natural history of 136 children. AB - In a mass screening programme, 251 children with isolated microhaematuria were detected. Of these 251 children, 115 were excluded from the study because of microhaematuria secondary to a specific cause. The remaining 136 children were diagnosed as having asymptomatic isolated microhaematuria (ASH). Of these 136 children, 23 had evidence of urinary abnormalities in their family members. Red blood cell casts were evident in 31 children at their initial visit or during the follow-up period. Ten children had one or more episodes of macrohaematuria during the study. Renal biopsy was performed in 19 children because of indications of glomerular disease, and 13 of these 19 children had mild to moderate glomerulonephritis. None of these 136 children developed hypertension or renal impairment after a mean period of 7.4 years (range 6-13 years). Thirty-five children had normal urinary findings within 6 years of their initial visit, and 100 have had persistent microhaematuria without proteinuria throughout the follow up period. The other child had microhaematuria with proteinuria greater than 1 g/m2 per day at the end of the study. This study suggests that the prognosis of ASH is good, and that renal biopsy is not indicated for children with ASH. PMID- 1911141 TI - What protein intake is recommended for nephrotic children? PMID- 1911142 TI - Microheterogeneity of urinary albumin and tubular proteinuria in juvenile diabetes mellitus. AB - We studied differential urinary albumin excretion by a double one-dimensional gel electrophoresis with decyl sodium sulphate-polyacrylamide gel electrophoresis in the first, and isoelectric focusing in the second dimension in 37 diabetic children and 20 healthy subjects. In addition, total proteins, albumin, beta 2 microglobulin and molecular size distribution of urinary proteins were measured, the latter using sodium dodecyl sulphate-polyacrylamide gel electrophoresis. Whilst albuminuria was not significantly different from controls we found an increased microheterogeneity of urinary albumin in 38% of patients. In addition, low molecular weight protein (P less than 0.05) and beta 2-microglobulin excretion (P less than 0.01) were elevated. It is suggested that the appearance of highly heterogenous albumin in the pI range of 5.3-5.9 is the result of a decreased tubular reabsorption. PMID- 1911143 TI - What investigations are appropriate in a teenage girl with chronic renal failure who has primary amenorrhea? PMID- 1911144 TI - Angiotensin converting enzyme inhibitors for reduction of proteinuria in children with steroid-resistant nephrotic syndrome. AB - The effects of angiotensin converting enzyme inhibitors (ACEI) on proteinuria, renal function, and serum proteins were evaluated in six children with steroid resistant nephrotic syndrome and proteinuria of 3-15 g/24 h (277 +/- 47 mg/m2 per hour). Following ACEI, proteinuria decreased from 7,408 +/- 2,385 (mean +/- SEM) to 3,746 +/- 1,395 mg/24 h (P less than 0.05). Creatinine clearance was 87.8 +/- 22.6 before and 96.4 +/- 23.6 ml/min per 1.73 m2 after ACEI. In two patients, inulin and para-aminohippuric acid clearances were normal before and after ACEI, together with parallel reductions of urine protein of 50% and 46%. Clearance of total protein was reduced by 56% following ACEI, compared with reduction in the clearance of gamma globulin by 58% and albumin by 39.5%. No significant change was seen in blood pressure, serum albumin, or total protein following ACEI. After ACEI, diuretic doses were able to be reduced or eliminated in three patients. Reduction of proteinuria was sustained during a followup period of 11-20 months in three patients. ACEI may be of benefit in the clinical management of children with steroid-resistant nephrotic syndromes, allowing reduction in diuretic requirements. PMID- 1911146 TI - Increased monocyte-dependent suppression of polyclonal activation of B lymphocytes from cystinotic children. AB - In infantile cystinosis the amino acid cystine preferentially accumulates in phagocytic cells, polymorphonuclear leucocytes (PMN) and monocytes, rather than in lymphocytes. We previously described functional abnormalities in the oxidative metabolism and locomotion of cystinotic PMN and monocytes. The present study shows an abnormal lymphocyte polyclonal activation as evidenced by a decreased immunoglobulin (Ig) production and generation of Ig-containing cells (ICC) in cultures of peripheral blood mononuclear cells (PBMC) from cystinotic children upon stimulation with pokeweed mitogen and Staphylococcus aureus Cowan I. However, monocyte depletion from cystinotic PBMC fully reconstituted Ig production and ICC generation, indicating: (1) the presence of an increased monocyte-dependent suppression on lymphocyte polyclonal activation, and (2) that the intrinsic ability of cystinotic lymphocytes to respond to polyclonal stimulation was preserved. The increased cystinotic monocyte-dependent suppressive effect was not mediated by prostaglandin E2 (PGE2) since its production by cystinotic PBMC upon polyclonal activation was not different from that of controls. In addition, the sensitivity of cystinotic lymphocytes to the immunosuppressive effect of varying concentrations of exogenous PGE2 was similar to that of controls. Finally, indomethacin and 2-mercaptoethanol, two agents able to scavenge hydroxyl (.OH) radicals, restored Ig production by cystinotic PBMC, suggesting a role for reactive oxygen species in the increased cystinotic monocyte-dependent suppression. PMID- 1911145 TI - Redistribution of cellular energy following renal ischemia. AB - In order to elucidate the pattern of redistribution of cellular energy and the restoration of basic cellular metabolism following an ischemic renal insult, suspensions enriched in proximal tubule segments were studied after 45 min of bilateral artery occlusion and 15 min and 2 h of reflow from rats given either normal saline (control), ATP-MgCl2 (which enhances postischemic recovery of ATP), or alpha, beta-methyl adenosine diphosphate (AMPCP), which inhibits nucleotide degradation during ischemia. In non-ischemic control animals, approximately half of the energy is distributed to functional pump activity and half directed for non-transport purposes. When cellular ATP is reduced to 56% of control values, functional pump activity is significantly reduced to 61% of control, while energy delegated for non-transport purposes is decreased by a significantly smaller increment to only 78% of control at 15 min of reflow. In animals given ATP-MgCl2, the cellular and metabolic profile at 15 min of reflow was no different from ischemic control animals with cellular ATP levels similar at 58%. However, by 2 h, cellular ATP levels had increased significantly to 74%, and this was associated with a redistribution of cellular energy to functional pump activity (119% of control) with little change in non-transport function (76%). In animals treated with AMPCP, the cellular ATP levels were 74% of controls, similar to ATP MgCl2-treated rats after 2 h of reflow. Despite the differences in reflow interval, the distribution of cellular energy was similar (functional pump activity 120% and non-transport activity 79%). By 2 h, cellular ATP was at 95% and both functional pump activity and non-transport activity were 100%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1911147 TI - Somatic growth in corticosteroid-treated rats with passive Heymann nephritis- effects of recombinant human growth hormone on growth impairment. AB - We evaluated the efficacy of recombinant human growth hormone (r-hGH) on corticosteroid (CS)-induced growth-impaired rats with proteinuria (passive Heymann nephritis. R-hGH (2 IU twice daily) improved growth in rats treated with 20 mg/kg per day of prednisolone succinate in our 4-week study. Although plasma hGH was significantly increased in rats treated with r-HGH, plasma insulin-like growth factor-1 levels were not different between treated and untreated rats. The food utilization rate was significantly improved by r-hGH. R-hGH did not affect proteinuria, renal function, or calcium and phosphate metabolism. Our results suggest that r-hGH may be effective in improving growth impairment due to CS administration. PMID- 1911148 TI - Renal transplantation in patients with classical haemolytic-uraemic syndrome. AB - Eighteen records from children with renal transplants (RT) and classical haemolytic-uraemic syndrome (HUS) were reviewed. The mean oliguric period was 17.9 +/- 7.5 days; the interval between acute phase and end-stage renal disease (ESRD) was 9.3 +/- 5.2 years. HUS was the most frequent cause of renal transplantation (23.4%). There were no significant differences between patients with HUS and controls (children with RT but without HUS), regarding renal function, frequency of rejections, renal survival (HUS 65%, controls 57%) or patient survival (94.4% and 96.6%, respectively) after 9 years. None had clinical or histopathological evidence of HUS recurrence in the allograft. Of all children with living-related donors (LRD), renal survival after 3 years was longer for those who received cyclosporin A (CSA) (HUS and controls 86%) than for those who did not receive it (HUS 50%, controls 53%). Classical HUS is a frequent cause of ESRD in Argentina. The duration of the acute oliguric period is a good predictor of the likelihood of progression to chronicity. In the classical form of HUS there is no recurrence in the allograft. CSA and LRD can be used without risk in renal transplantation of children with classical HUS. PMID- 1911149 TI - Psychosocial adjustment to end-stage renal failure: comparing haemodialysis, continuous ambulatory peritoneal dialysis and transplantation. AB - Seventy-three children and adolescents in end-stage renal failure (ESRF) undergoing haemodialysis (n = 32), continuous ambulatory peritoneal dialysis (CAPD) (n = 28) or with a functioning transplant (n = 13), were assessed, with their parents, on adjustment to dialysis and psychological functioning. Quantitative assessment techniques were used; the three treatment groups were compared using the Mann-Whitney U test. Findings showed a number of advantages of transplantation over dialysis, and of CAPD over haemodialysis. Children with transplants suffered less functional impairment (P = 0.007), less social impairment (P = 0.001) and fewer practical difficulties associated with treatment (P = 0.000) than children undergoing dialysis. Parents of children with transplants also reported fewer practical difficulties than parents of children on dialysis (P = 0.002). Dialysis and transplant groups did not differ on children's or parents' reports of psychological stress associated with treatment, parents' reports of marital strain, children's and parents' levels of anxiety and depression or children's behavioural disturbance. Compared with children undergoing hospital haemodialysis, those using CAPD suffered less social impairment (P = 0.004), reported better adjustment to dialysis (P = 0.031) and fewer practical problems associated with treatment (P = 0.005), had lower depression scores (P = 0.054), and showed less behavioural disturbance (P = 0.013). Parents of children undergoing either CAPD or hospital haemodialysis reported similar practical difficulties, psychological stress or marital strain associated with treatment, but mean depression and anxiety scores were lower in the parents of children undergoing CAPD (P = 0.042 and P = 0.054).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1911150 TI - Kidney biopsy prior to cyclophosphamide therapy in primary nephrotic syndrome. AB - The study includes 30 children, 10 each with minimal change nephropathy (MCNS), diffuse mesangial proliferative glomerulonephritis (MesPGN) and focal segmental glomerulosclerosis (FSGS). Indications for kidney biopsy were: steroid resistance in 12 cases, and frequent relapses on maintenance steroid therapy in 18 cases. A 2-year remission was achieved by cyclophosphamide therapy in 6 patients with FSGS, 8 patients with MCNS and 8 patients with MesPGN. In terms of initial response to corticosteroids, only 3 of 8 patients with early steroid resistance responded to cyclophosphamide therapy compared with 3 of 4 with late steroid resistance and 16 of 18 with frequent relapses on maintenance steroid therapy. Response to cyclophosphamide therapy correlates better with the initial corticosteroid response than renal histopathology. A kidney biopsy prior to administration of cyclophosphamide is not essential in patients who respond to initial corticosteroid therapy. PMID- 1911151 TI - Fungal peritonitis in children treated with peritoneal dialysis and gastrostomy feeding. AB - Feeding gastrostomies were placed in three children treated with chronic peritoneal dialysis at our center because of persistent, severe malnutrition and inadequate growth. Two had frequent fungal infections of the gastrostomy site and all three developed Candida peritonitis which occurred at 1 month, 2 months and 2 years after insertion of gastrostomy. Complications included multiple intra abdominal adhesions, abscess formation and loss of peritoneal function necessitating transfer to hemodialysis. The presence of a gastrostomy may predispose to the development of fungal peritonitis with its high morbidity and should be avoided in children on chronic peritoneal dialysis. PMID- 1911152 TI - New strategies in immunosuppression. AB - This article reviews recent papers relating to immunosuppressives and attempts to categorise the bewildering number of new reagents according to their effects on the immune response. It is apparent that the majority of groups are concentrating on reagents which, like cyclosporin A, are predominantly directed at T cells (42% of the last 200 papers in Transplantation, Transplant International and Transplantation Proceedings). The major change in strategy which is occurring relates to the rapidly increasing use of reagents directed against T cell subsets, especially those directed against the interleukin-2 receptor and CD4 positive T cells. This groups's share of the "market" has risen from 2% to over 12% within 5 years. New successful monoclonal antibodies include reagents directed against antigen-presenting cells and against molecules directly involved in cell adherence. The use of donor bone marrow or subsets of cells from donor bone marrow as inducers of non-reactivity, especially to solid organ grafts, is certainly one of the most exciting of the non-antibody protocols. It is encouraging that relatively specific immunosuppression can be induced in animals by combinations of specific and non-specific reagents as well as by specific reagents alone. This will facilitate the introduction of specific protocols into the human situation, and this strategy holds out great hope for the future. Unfortunately, one of the most effective ingredients of such combination therapies in animal models (anti-CD4) appears to have its tolerogenic potential abrogated by cyclosporin A and FK-506.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1911155 TI - Second meeting of the European Society of Paediatric Urology, 12-13 April 1991, Beaune, France. PMID- 1911156 TI - Renal transplantation in children: an American view from the bridge. AB - Performance of renal transplants in children frequently necessitates transfer of patients from the care of a local pediatric nephrologist to a regional, tertiary care center that is specially equipped to carry out organ transplantation. This shift in institutional affiliation can be the cause of some difficulties in treating these complicated patients including: (1) disparities in the expected outcome of the renal transplant procedure; (2) co-ordination and timely completion of the pre-operative evaluation; (3) proper handling of transfers of patients between medical centers and inter-physician communication; (4) psychosocial pressures encountered by parents when their children are under the care of two teams of physicians. It is recognized that the relationship between the referring pediatric nephrologist and the transplant physician is paradigmatic of the association that develops between a general practitioner and a specialist. With this in mind, we offer some tentative suggestions on how to improve the therapeutic alliance between referring pediatric nephrologists and transplant surgeons, in the hope that this will improve the care of all pediatric transplant recipients. PMID- 1911153 TI - Practical aspects in the use of cyclosporin in paediatric nephrology. AB - Many factors must be considered for the effective and safe use of cyclosporin A (CsA) in paediatric nephrology. Detailed knowledge of the variable bioavailability, tissue distribution, and metabolism, as well as causes which lead to their alteration are necessary. Factors which affect the activity of the mixed function oxidase system cytochrome P-450 must be considered, i.e. liver dysfunction and many drugs. Precise knowledge of the CsA determination method and the spectrum of metabolites is essential. In children with renal transplants, a body surface area-related dose will better meet the dose requirements than a body weight related-dose. For drug level monitoring whole blood rather than plasma should be used, and the parent drug level should be the main determinant; elevated metabolite levels may be important in suspected nephrotoxicity or liver dysfunction. Pharmacokinetic profiles are necessary to discover absorption problems or increased CsA clearance rates which necessitate shorter dosing intervals. In children with steroid-dependent minimal change nephrotic syndrome, remission without steroids is maintained as long as CsA is given. The appropriate starting dosage is 150 mg/m2 per day; trough level monitoring is mandatory to prevent nephrotoxicity and to confirm adequate immunosuppressive drug levels which should be 80-160 ng/ml (parent drug level). Although the benefit of CsA has been reported in some cases of lupus erythematosus, its use should be restricted to severe cases only until its efficacy and safety has been confirmed in controlled trials. PMID- 1911157 TI - Clinical quiz. Chronic potassium deficiency. PMID- 1911154 TI - Prostanoids in paediatric kidney diseases. AB - Prostanoids belong to the growing family of eicosanoids, which are all derived from arachidonic acid. Prostanoids act as modulators and mediators in a large spectrum of physiological and pathophysiological processes within the kidney. On the one hand, the potent vasoconstrictor and platelet-aggregating thromboxane (TX) A2 is involved in the pathophysiology of a variety of glomerular diseases, such as haemolytic-uraemic syndrome and immune-mediated glomerulopathies. Prostaglandin (PG) E2, on the other hand, interferes with tubular electrolyte and water handling. Clinical data support the hypothesis that this member of the prostanoid family contributes to the pathophysiology of Bartter's syndrome, hyperprostaglandin E syndrome, idiopathic hypercalciuria and renal diabetes insipidus. Both prostanoids, TXA2 and PGE2, are involved in the pathophysiology of obstructive uropathies. The physiological and protective role of renal vasodilator prostanoids (PGI2 and PGE2) has been studied during treatment with non-steroidal anti-inflammatory drugs. Part of the pharmacological effects of frusemide and converting enzyme inhibitors is mediated by PGI2 and PGE2. The role of renal prostanoids in cyclosporine toxicity is still equivocal. Future investigations on the physiological and pathophysiological role of renal prostanoids will have to consider the multiple interactions between prostanoids on the one hand, and classical hormones and other mediators (e.g. cytokines) on the other hand. PMID- 1911158 TI - Response to growth hormone in a child with Bartter's syndrome. PMID- 1911160 TI - Acquired immunodeficiency syndrome (AIDS)--data as at 1 July 1991. PMID- 1911159 TI - Idiopathic hypercalciuria. PMID- 1911161 TI - Diarrhoeal Diseases Control Programme. Global activities. PMID- 1911162 TI - Rubella. Surveillance to December 1990. PMID- 1911163 TI - Measles. Outbreak in New York City, 1990-1991. PMID- 1911165 TI - Programme for the control of acute respiratory infections. Recent developments. PMID- 1911164 TI - International travel and health. Advice for travellers at high altitudes. PMID- 1911166 TI - Human listeriosis. Annual surveillance report, 1989. PMID- 1911167 TI - Expanded programme on immunization. Safety and efficacy of high titre measles vaccine at 6 months of age. PMID- 1911168 TI - Hepatitis C (parenterally transmitted non-A, non-B hepatitis). PMID- 1911169 TI - Anthrax. Human cutaneous anthrax--a case report. PMID- 1911170 TI - Observations of a physician/patient. PMID- 1911171 TI - Of grants and curricula and treatment costs and BSE and things. PMID- 1911172 TI - Strategies for maintaining oncology curriculum time amid pressures to cut classroom hours. AB - A decade of experience with the oncology course offered within the second year pathophysiology curriculum at the Washington University School of Medicine is reviewed. The number of classroom hours allotted to this course has steadily decreased from 28 to 6 hours. Causes of this downward trend include the introduction of new subject matter into the curriculum and the desire for more independent study time. Strategies for maintaining or increasing the number of lecture hours are discussed. Videotaping the principles of surgical, medical, and radiation oncology enables the coursemaster to return the classroom emphasis to the patient as illustration. PMID- 1911173 TI - Women's knowledge of and attitude toward breast cancer in a developing country: implications for program interventions--results based on interviewing 500 women in Saudi Arabia. AB - We interviewed 500 adult females without personal history of any type of cancer to assess their awareness and attitude toward various aspects of breast cancer. The mean age (SD) of participants was 31.6 (+/- 8.5) years with a range of 18 to 62 years. After control for level of education, age was not found to be a statistically significant factor that influenced participants' performance. Also not statistically significant was the history of having a relative who had cancer. Conversely, education was the only examined factor that correlated with interviewees' awareness and attitude. Individuals with university or higher education (level III) were more knowledgeable (statistically significant) than uneducated or those with only primary schooling (level I), or those participants who only had intermediate or high school education (level II). On the other hand, the responses of those individuals with education level I generally performed in a fashion similar to those at education level II. The general outcome of this exercise was that unacceptably high proportions of females at all education levels were either wrong or uncertain about some fundamental aspects of breast cancer etiology, risk factors, clinical features, detection methods, and management. Also shown was the relatively high percentages of those, particularly in education level I, who held misconceptions about unconventional management or the complications of conventional methods. We conclude that academic education alone is not enough to assure that recommended health behaviors will be adopted. For establishing cancer health education or cancer prevention and early detection programs, primary care physicians and community cancer centers should work jointly. Brief guidelines are proposed. PMID- 1911174 TI - Practice and effectiveness of breast self examination: a selective review of the literature (1977-1989). AB - From a review of the literature on studies on breast self examination (BSE), it is evident that BSE functions as an effective preventive health behavior. Only 19% to 40% of women practice BSE on a monthly basis, and there is no strong evidence that women who practice monthly BSE perform the procedure correctly. Confidence in BSE performance, prior BSE instruction, and finding some way to remember to do BSE were the factors most positively associated with frequent BSE practice. Women need to be given the facts about breast cancer and information about early detection methods and also need to be taught BSE in such a way that they feel confident in their BSE skills. The most effective way to teach BSE is to teach the woman on her own breasts. Since BSE is a skill, an accurate assessment of the learners' BSE techniques is necessary to adequately evaluate BSE teaching methods. PMID- 1911175 TI - Excessive test costs in clinical research protocols. AB - The escalation of health care costs has become an essential part of clinical research. Some clinical research protocols appear to require excessive laboratory testing. A review of an adjuvant breast cancer trial compared the costs of the required laboratory tests to those deemed "essential" to meet the goals of the study. A reduction of 59% in the laboratory tests over 6 1/2 years was accomplished. It is apparent that a significant reduction in cost can be accomplished. With such efforts, greater participation in clinical trials might occur. These observations are relevant in cancer education programs that involve patients on research protocols. PMID- 1911176 TI - The use of recorded interviews to enhance physician-patient communication. AB - Audio recordings were made of the initial interview conducted between a cancer physician and 29 patients at the time of initial diagnosis and treatment planning. The tape recordings were then given to these patients to allow review as often as desired. Follow-up questionnaires were collected to evaluate this experience. We found that the recording session was well accepted and that the taped interviews were frequently reviewed, usually with family and friends. Despite the patients' initial feelings that both diagnosis and treatment plan were well understood, most felt that listening to the taped interview provided new information and a clearer understanding about their cancer care. The results of our study support the use of recorded interviews as a valuable tool to help patients and families cope with cancer and a successful method to improve communication with physicians. PMID- 1911177 TI - Alcohol and cancer. An instructive association. PMID- 1911178 TI - Lifestyle and leukaemia. PMID- 1911179 TI - The current status of scientific research and hormonal treatments for carcinoma of the prostate. PMID- 1911180 TI - Coagulation and cancer. PMID- 1911181 TI - Are cancer cells acidic? PMID- 1911183 TI - Cellular cytotoxicity mediated by isotype-switch variants of a monoclonal antibody to human neuroblastoma. AB - The biological property of an antibody is determined by its antigen binding characteristics and its isotype-related effector functions. We have established monoclonal antibodies of different isotypes by stepwise selection and cloning of the hybridoma CE7. The original CE7 secretes an IgG1/kappa (CE7 gamma 1) antibody that recognises a 185 kD cell surface glycoprotein expressed on all human sympatho-adrenomedullary cells. Isotype-switch variants were isolated in the following sequence: from the original CE7 gamma 1, CE7 gamma 2b variants were isolated, and from a CE7 gamma 2b variant CE7 gamma 2a variants were isolated. The antibodies of three different isotype variant cell lines possess identical antigen binding characteristics, but display distinct effector functions as demonstrated by antibody dependent cell-mediated cytotoxicity (ADCC). ADCC was performed with the neuroblastoma line IMR-32 as the target cells, and different FcR gamma positive cells were either freshly isolated from human peripheral blood leukocytes or cultured for 6-10 days and tested as potential effector cells. Tumour lysis mediated by monocyte-derived macrophages depended on the presence of CE7 gamma 2a antibodies; antibodies from the CE7 hybridomas of gamma 2b and gamma 1 isotypes were virtually inactive in ADCC assay. Pre-exposure of macrophages to rIFN-gamma enhanced their ADCC activity, a result that is compatible with the notion that the high affinity Fc IgG receptor (FcR gamma I/CD64) is involved in the triggering of ADCC in macrophages. In contrast to macrophages, mononuclear cells, nonadherent cells and monocytes displayed considerable non-specific lytic activity, which was little influenced by the presence of antibody regardless of the isotype added. PMID- 1911184 TI - Human tumour-associated NK cells secrete increased amounts of interferon-gamma and interleukin-4. AB - Numerous interactions between malignant and stromal/inflammatory cells take place within solid human tumours, which are mediated, in part, by the release of signalling proteins called cytokines. In the present study, we have compared the secretion of two important immunomodulatory cytokines, IFN-gamma and IL-4 by individual, immunophenotyped NK cells freshly isolated from either malignant tumour biopsies, or peripheral blood samples from patients with ductal invasive breast cancer. Due to the marked heterogeneity amongst cells isolated from these clinical samples, we have employed a technique called the reverse haemolytic plaque assay to identify and enumerate cytokine-secreting cells at the single cell level. Our data indicate that NK cells isolated directly from the tumour site secrete more IFN-gamma and IL-4 than NK cells from the blood of the same patients. However, a greater proportion of CD16+ cells from both sources in breast cancer patients secreted IFN-gamma than of those from the blood of healthy donors. We also show that factors secreted by the human breast cell lines, MCF-7 and MDA-231 PN9, were able to mimic the stimulatory influence of the tumour microenvironment on secretory activity of NK cells. PMID- 1911182 TI - Nucleoside salvage and resistance to antimetabolite anticancer agents. PMID- 1911185 TI - A prolactin-dependent, metastasising rat mammary carcinoma as a model for endocrine-related tumour dormancy. AB - In order to study the growth kinetics of breast tumours during long-term hormonal withdrawal, we developed a transplantable, invasive mammary carcinoma EMR-86 that originated in a female WAG/Olac rat bearing a subcutaneously implanted oestrogen pellet (EP). Outgrowth of transplanted tumours occurs only in the presence of an EP, and metastases are formed in lungs and regional lymph nodes. Subsequent EP removal induces rapid regression. However, tumours do not disappear completely, as small nodules persist. These dormant tumour remnants can be restimulated even after long periods. Because EP-stimulated tumours regressed after treatment with bromocriptine and dormant tumours in non-oestrogenized rats grew out after treatment with perphenazine, prolactin is the major growth-stimulating hormone in this model. Cell kinetics in the growing, regressing and dormant phase were studied by immunocytochemical detection of DNA-incorporated bromodeoxyuridine (BrdUrd) in tissue sections. BrdUrd labelling indices decreased from 21.6 +/- 3.0% to less than 1% within 7 days after EP removal. After prolonged hormonal withdrawal (up to 90 days) BrdUrd-labelled tumour cells could always be demonstrated (range 0.4-0.8%), without a concomitant increase in tumour volume. Additional treatment either with bromocriptine or with ovariectomy could not significantly reduce this residual proliferative activity, as demonstrated by continuous BrdUrd labelling experiments. The results indicate that in vivo dormancy may represent a steady state of cell division and cell loss, rather than an accumulation of cells in a non-cycling G0 state. PMID- 1911186 TI - In vitro drug sensitivity of normal peripheral blood lymphocytes and childhood leukaemic cells from bone marrow and peripheral blood. AB - In vitro drug sensitivity of leukaemic cells might be influenced by the contamination of such a sample with non-malignant cells and the sample source. To study this, sensitivity of normal peripheral blood (PB) lymphocytes to a number of cytostatic drugs was assessed with the MTT assay. We compared this sensitivity with the drug sensitivity of leukaemic cells of 38 children with acute lymphoblastic leukaemia. We also studied a possible differential sensitivity of leukaemic cells from bone marrow (BM) and PB. The following drugs were used: Prednisolone, dexamethasone, 6-mercaptopurine, 6-thioguanine, cytosine arabinoside, vincristine, vindesine, daunorubicin, doxorubicin, mafosfamide (Maf), 4-hydroperoxy-ifosfamide, teniposide, mitoxantrone, L-asparaginase, methotrexate and mustine. Normal PB lymphocytes were significantly more resistant to all drugs tested, except to Maf. Leukaemic BM and PB cells from 38 patients (unpaired samples) showed no significant differences in sensitivity to any of the drugs. Moreover, in 11 of 12 children with acute leukaemia of whom we investigated simultaneously obtained BM and PB (paired samples), their leukaemic BM and PB cells showed comparable drug sensitivity profiles. In one patient the BM cells were more sensitive to most drugs than those from the PB, but the actual differences in sensitivity were small. We conclude that the contamination of a leukaemic sample with normal PB lymphocytes will influence the results of the MTT assay. The source of the leukaemic sample, BM or PB, does not significantly influence the assay results. PMID- 1911187 TI - Genetic alterations within the retinoblastoma locus in colorectal carcinomas. Relation to DNA ploidy pattern studied by flow cytometric analysis. AB - Alterations within the retinoblastoma (Rb) gene, as detected by the VNTR probe p68RS2.0, and flow cytometric DNA pattern have been analysed in 255 colorectal carcinomas. A total of 35.3% of the tumours had alterations within the Rb gene. Amplification of one allele was demonstrated in 29.5% of the tumours, and loss of heterozygosity was found in 11.5%. No association was found between amplification within the Rb gene and clinicopathological characteristics of the patients. The high frequency of alterations demonstrated within the Rb gene, suggests that this gene is involved in colorectal carcinogenesis with amplification as by far the most abundant genetic alteration. This may imply that the Rb gene has an oncogene like function in colorectal carcinomas, rather than acting as a tumour suppressor gene. Sixty-three per cent of the carcinomas were DNA aneuploid, and a significant association was demonstrated between amplification within the Rb gene and DNA aneuploidy (P less than 0.01). Two other chromosome loci were analysed, on chromosome 1p (probe pYNZ2) and on chromosome 2p (probe pYNH24), respectively. On chromosome 1p, heterozygous loss was found in 22.2% of the tumours, indicating an involvement of this chromosome in a subset of colorectal carcinomas. PMID- 1911188 TI - Comparative study of the influence of pregnancy and hormonal treatment on mammary carcinogenesis. AB - Since it has been shown that pregnancy protects the mammary gland from chemically induced carcinogenesis, this study was designed with the dual purpose of determining whether treatment of young virgin rats with the placental hormone chorionic gonadotropin (hCG) mimics pregnancy-induced changes in the tumourigenic response of the mammary gland and also whether the effect induced by both pregnancy and hormonal treatments was transitory, or a more permanent one, exerting the same effect when the period of time between delivery or termination of treatment and exposure to the carcinogen is lengthened. Virgin Sprague-Dawley rats were utilised in two experimental protocols. For protocol I, 50 day-old rats were either mated (Group II), or started receiving a daily intraperitoneal injection of 100 IU hCG (Group III) at age 50. Age-matched untreated virgin rats were used as controls (Group I). Twenty-one days after either delivery or termination of treatment all the animals received an intragastric dose of 8 mg DMBA/100 gbw. For the second protocol, 50 day-old virgin rats were also mated (Group V) or were treated with hCG for 21 days (Group VI); the resting period between delivery or termination of treatment was lengthened to 63 days, at which time they received a dose of DMBA. Age-matched controls (Group IV) received DMBA only. Tumourigenesis was evaluated 24 weeks post-carcinogen administration in all the groups. Pregnancy and hCG followed by the 21-day resting period significantly depressed mammary carcinogenesis to 11% and 6% respectively, compared with 63% in control animals. When the resting period was prolonged to 63 days there was also a significant depression in adenocarcinoma incidence to 9% in pregnancy (Group IV) in which it was observed that tumour incidence was also reduced as a consequence of aging at the time of exposure to the carcinogen. These results clearly indicate that hCG is as efficient as pregnancy and significantly reduces mammary carcinogenesis, and that the protective effect of both pregnancy and hCG treatment is long-lasting and both are more efficient than aging in reducing mammary carcinogenesis. PMID- 1911189 TI - 31P nuclear magnetic resonance spectroscopy, histology and cytokinetics of a xenografted hypopharynx carcinoma following treatment with cisplatin: comparison in three sublines with increasing resistance. AB - The changes in the phosphorus metabolism of a xenografted hypopharynx carcinoma (Hyp 1), sensitive to cisplatin (CDDP), were compared to those occurring in two sublines of the tumour, characterised by moderate or high resistance to CDDP (Hyp 1/H and Hyp 1/R) following, i.p. administration of 4, 8 or 12 mg CDDP/kg-1. The investigations were performed by in vivo 31P nuclear magnetic resonance (NMR) spectroscopy. Parallel to the NMR experiments, the cytokinetic and histological alterations in the tumours were studied under the same experimental conditions. No mentionable differences in the levels of the main phosphorus-containing metabolites could be detected between the three tumour lines before treatment. Following application of CDDP, the alterations in the NMR spectra were clearly related to the degree of tumour response. The most sensitive and earliest marker of tumour regression was a decrease in the phosphomonoester/phosphodiester ratio, parallelled by a gradual increase in the phosphocreatine/inorganic phosphorus quotient. In the resistant tumour lines Hyp 1/H and Hyp 1/R non-responding tumours showed alterations in the 31P NMR spectrum which were similar to those observed during uninfluenced tumour growth. Marked changes in the 31P NMR spectrum were always associated with severe cytotoxic lesions following therapy. The results suggest that the changes detected by 31P NMR spectroscopy following chemotherapy with CDDP are response-specific. PMID- 1911190 TI - Patients receiving murine monoclonal antibody therapy for malignancy develop T cells that proliferate in vitro in response to these antibodies as antigens. AB - Peripheral blood mononuclear cells (PBMCs) were obtained from patients receiving radioactive murine monoclonal antibody (MAb) therapy for malignant epithelial tumours, as well as normal controls, and were tested for the ability of T cells to proliferate in vitro in the presence of the MAb administered for therapy (HMFG1), and another isotypically matched antibody of irrelevant specificity (11.4.1). We studied 13 patients who had one (ten patients) or two (three patients) courses of MAB treatment, 11 age matched patients with the same histologic types of tumours, that had not received MAbs, and four normal controls. There was a consistent dose dependent in vitro T cell proliferation in 11 of the 13 patients after MAb therapy. This was not observed in the pre-therapy group of patients or normal controls, where the T cell proliferative responses remained baseline. The mean stimulation index (S.I.) in the post-therapy group was significantly higher than that of the pre-therapy patients and that of normal controls. When the in vitro T cell proliferative responses of these patients were measured in the presence of HMGF1 MAb (IgG1) and an isotypically identical, but idiotypically unrelated 11.4.1 MAb (IgG1), there was no statistically significant difference in the mean S.I. For HMFG1 vs 11.4.1 for the whole group of treated patients. When patients were separated into those who received one and those who received two MAb treatments, a significant increase in the mean S.I. was observed in the presence of HMFG1, in the group of patients receiving two treatment courses, suggesting the generation of T cells with specificity for the idiotypic component of the administered murine immunoglobulin. In order to further characterise these in vitro cellular responses we incubated PBMCs with and without an optimal concentration of the MAb (100-300 micrograms ml-1), as defined by the proliferation assay, and compared the differences in cell subpopulations. A significant increase in the percentage of cells expressing interleukin-2 receptors (IL-2R) was observed after MAb stimulation. The percentage of CD4+ lymphocytes and the CD4/CD8 ratio increased in all the cases studied, after MAb stimulation, where the percentages of B cells and NK cells remained relatively constant at less than 2-3% of the total population. We therefore conclude that murine MAbs administered to patients with cancer can lead to the generation of T cells which can recognise these MAbs as antigens when presented appropriately in vitro. The main proliferating population appears to be T helper CD4+ lymphocytes which following stimulation can release interleukin-2 leading to the expression of high levels of IL-2R. PMID- 1911191 TI - Breast cancer proliferation measured on cytological samples: a study by flow cytometry of S-phase fractions and BrdU incorporation. AB - Cell kinetics have been shown to be an important predictor of clinical evolution of operated breast cancer. We established a method for the estimation of the proliferative activity of tumour cells obtained by fine needle sampling without aspiration (FNS), using simultaneously S-phase fractions (SPF) measured on DNA histograms and 5-bromodeoxyuridine (BrdU) labelling index (BLI) measured by flow cytometry. Biparametric BrdU/DNA flow cytometry could be performed in 122 of 189 (65%) consecutive patients. The mean BLI of the cytologically malignant FNS (118) was of 3.0 and the median of 2.2%. One hundred and forty-eight DNA histograms (78%) were suitable for SPF analysis, of which 141 presented malignant cells, showing a mean of 4.5 and a median of 3.5%, comparable to BLIs. These results were obtained from fluorescence peak area histograms with doublet discrimination and background subtraction allowing the measurements of SPFs as low as 0.4%. An excellent correlation was thus observed between BLIs and SPFs, for the 94 cases for which both results were available (r = 0.85). Infrequent discordances (9%) were noted with SPFs considerably higher than BLIs. Seven patients had three consecutive FNS of their tumour at weekly intervals before treatment. Some variability in the proportions of multiple subpopulations of tumour cells was observed on the DNA histograms. In contrast, proliferation indices (SPF or BLI) were reproducible, suggesting homogeneous growth rates. We conclude that an estimation of the proliferative activity of breast tumours at any stage of the disease is possible routinely by SPF and/or BLI analysis of FNS. At least one quantitative proliferation index could be obtained for 91% of patients. PMID- 1911192 TI - Enhancement of pulmonary tumour seeding by human coagulation factors II, IX, X- an investigation into the possible mechanisms involved. AB - Warfarin inhibits metastasis in the animal model and injection of the Warfarin dependent coagulation factor complex II, IX, X enhances pulmonary metastasis in the same model. We have studied two possible mechanisms responsible for the observed effect. Mtln3, rat mammary carcinoma cells, radiolabelled with 5-(125) Iodo-2'-deoxyuridine (IUDR) were injected intravenously in female Fisher 344 rats either alone or in combination with factor complex II, IX, X or bovine serum albumin. Following sacrifice at various intervals, measured lung radioactivity was significantly higher (20%) in animals administered cells with the factor complex than in the other two groups (P less than 0.001, ANOVA and Student's t test). These results indicate increased entrapment of tumour cells in the pulmonary microcirculation. In a second experiment, rat factor complex II, IX, X was prepared, and Mtln3 cells were then injected in female Fisher 344 rats alone or in combination with either human factor complex or rat factor complex. Following sacrifice, the number of pulmonary nodules in animals receiving cells with rat factor complex was similar to that in animals receiving human factor complex, and significantly higher than that in the control (P less than 0.001, ANOVA and Mann-Whitney), indicating that the observed enhancement of pulmonary seeding is unrelated to the xenogeneic properties of the human factor complex. PMID- 1911193 TI - Effects of cycloheximide on B-chronic lymphocytic leukaemic and normal lymphocytes in vitro: induction of apoptosis. AB - A number of reports indicate that protein synthesis is a requirement for the occurrence of apoptosis. In this study, the effect of the protein synthesis inhibitor cycloheximide (CHM) on spontaneous apoptosis of B-chronic lymphocytic leukaemia (B-CLL) cells, previously shown to occur when they are cultured in RPMI 1640 medium with autologous or heterologous serum, was examined. No definite inhibition of apoptosis was observed. Indeed, CHM-treatment augmented apoptosis in the B-CLL cultures and also induced apoptosis of cultured normal peripheral blood lymphocytes. Augmentation was dose-dependent for B-CLL cells over the concentration range 10(-6) M (0.28 micrograms ml-1) to 10(-2) M (2800 micrograms ml-1), resulting in 9% to 98% apoptosis respectively by 24 h of culture (r = 0.619, P = 0.0008). Normal lymphocytes were affected by CHM over the range 10(-4) M to 10(-2) M, resulting in 7% to 74% apoptosis respectively (r = 0.794, P = 0.0001). Inhibition of protein synthesis in these cells by CHM was virtually complete at a concentration of 10(-3) M. The findings are in accord with some recent reports indicating that suppression of protein synthesis by CHM does not inhibit apoptosis in all circumstances. They also illustrate the marked susceptibility of B-CLL cells, compared with normal lymphocytes, to the induction of apoptosis by this drug. The manner in which CHM triggers apoptosis of some cell types is at present uncertain. PMID- 1911194 TI - Flow cytometric DNA measurement and cytomorphometric analysis of formalin fixed rat mammary tumours. AB - Archival paraffin embedded material was used to examine whether additional quantitative criteria would be helpful to discriminate between histologically benign and malignant rat mammary tumours. To this end nuclear DNA content expressed as DNA ploidy index (DI) was measured using flow cytometry (FCM). A total of 63 benign and malignant mammary tumours were investigated. Thirteen out of 38 (34%) mammary carcinomas were DNA aneuploid against 0 out of 25 benign mammary tumours. Aneuploidy was not significantly increased in tumours showing histological signs of greater malignancy such as cribriform-comedo type or invasive growth. In addition to DI other quantitative criteria indicative for malignancy, such as mitotic count and nuclear morphometric characteristics, were estimated in 24 benign and malignant tubulopapillary tumours, a category where the histological classification may be difficult. It appeared that five out of nine noninvasive tubulopapillary carcinomas and six out of seven invasive carcinomas had abnormal values for either DI, mitotic count or nuclear area or for a combination of these parameters. Each single parameter however was abnormal only in a minority of the malignant tumours. In this respect our data are in accordance with the fact that rat mammary carcinomas are clinically and histologically less malignant than their human counterparts. PMID- 1911195 TI - Whole body hyperthermia and carboplatin: cytotoxicity for murine leukaemia and normal marrow. PMID- 1911196 TI - Reversal of adriamycin resistance by lonidamine in a human breast cancer cell line. PMID- 1911197 TI - Contacts between adults as evidence for an infective origin of childhood leukaemia: an explanation for the excess near nuclear establishments in west Berkshire? AB - The increasing tendency for people to work outside their home community--one of the most striking of modern demographic changes--has relevance to a recent aetiological hypothesis about childhood leukaemia: that a community's immune response to an underlying infection can be disturbed by increases in new social contacts. This was tested in the only 28 former county boroughs in which accurate comparisons of workplace data from the 1971 and 1981 censuses are possible- because their boundaries were left unaltered by the major reorganisation in 1974. After ranking the districts according to extent of commuting increase, a significant trend in leukaemia incidence was found at ages 0-14 (P less than 0.05) and a suggestive one at ages 0-4 (P = 0.055). Among ten similar sized groups of county districts ranked by commuting increase, the only significant increases (P less than 0.001) of leukaemia in 1972-85 at ages 0-4 and 0-14 were in the highest tenth for commuting increase. These excesses persisted after excluding Reading, a major part of an area where an excess of leukaemia has been linked to the nearby nuclear establishments at Aldermaston and Burghfield. This whole area has experienced greater commuting increases than 90% of county districts in England and Wales. The findings are consistent with other evidence supporting the above hypothesis; they also suggest that contacts between adults may influence the incidence of leukaemia in children. PMID- 1911198 TI - Death due to recurrence following curative resection of early gastric cancer depends on age of the patient. AB - This study was done to define the relationship between age at the time of surgery and the prognosis after curative resection for patients with an early gastric cancer. Three hundred and eighty-two patients were identified and 25 patients died of tumour recurrence. Overall, the cumulative survival rate was 94.9% at 5 years and 92.4% at 10 years. Patients with a recurrence of the gastric cancer tended to be older, were more likely to have large differentiated type of tumour and lymph node metastases were often present. Stratified into age-classified groups, the survival rate decreased with increase of age (for patients under age 34 years, 35 to 44, 45 to 54, 55 to 64, 65 to 74, over age 75 years, the 5-year survival rates were 100.0, 97.7, 97.6, 94.2, 94.1 and 84.4 (%]. Of the 25 patients with a tumour recurrence and who died, the survival time of 18 patients over age 55 years was significantly shorter than that of seven patients under age 54 years (median, 1.7 vs 5.6 years, P less than 0.05). The multivariate analysis showed that, over and above the differentiated type of tumour (P less than 0.01) and the presence of lymph node metastases (P less than 0.01), age was one of the prognostic factors (P less than 0.05). We conclude that age at the time of primary surgery is a significant factor in patients with an early gastric cancer. PMID- 1911199 TI - Epidemiological evidence for age-dependent regression of pre-invasive cervical cancer. AB - Data from the screening programme in British Columbia are used to test hypotheses about the natural history of cervical cancer, especially about progression and regression of preclinical lesions (dysplasia and carcinoma in situ). Three models are considered. A model without regression does not give an adequate fit of the data (P less than 0.001), and results in an implausible estimate of 33 years for the mean duration of pre-invasive lesions. A model with an equal regression rate at all ages still does not result in a good reproduction of the data. A good fit is achieved for a model with different regression rates in lesions that develop under and over age 34. Under age 34, 84% of the new lesions will regress spontaneously, with a 95% confidence interval of 76-92% regression. Over age 34, we estimate that 40% of the new lesions will regress. The average duration of dysplasia + CIS is 11.8 years, and the sensitivity of the Pap-smear is 80%. It is concluded that a considerable proportion of pre-invasive lesions in young women do not progress. The findings about progression and duration of pre-invasive lesions do not support the still prevailing tendency of frequently making Pap smears in young women. PMID- 1911200 TI - Elevated P53 expression correlates with a history of heavy smoking in squamous cell carcinoma of the head and neck. AB - Expression of the tumour suppressor gene p53 was examined in squamous cell carcinoma of the head and neck using two p53 antibodies, PAb 421 and PAb 1801. Elevated p53 expression was found in 67% of the 73 patients investigated. P53 expression was not found to correlate with whether the patient had been previously treated or not, nor any of the clinico-pathological parameters. However a correlation was found between the patients smoking history and positive p53 staining. Six out of seven non-smokers did not express p53 whereas 29 of 37 heavy smokers were found to have elevated p53 expression (P less than 0.005). Also, of a group of ten patients who had given up smoking more than 5 years ago, nine had elevated expression. Epidemiological studies have shown a correlation between heavy smoking and head and neck cancer. The present study indicate a genetic link for this correlation. PMID- 1911201 TI - Flow cytometric analysis of DNA ploidy and S-phase fraction from prostatic carcinomas: implications for prognosis and response to endocrine therapy. AB - We analysed ploidy and S-phase fraction (SPF) from 78 paraffin-embedded primary prostatic carcinomas by DNA flow cytometry. DNA aneuploidy and above median (4.2%) SPF were both associated with high tumour grade, large size of prostate and presence of distant metastases. Both aneuploidy and high SPF (greater than 4.2%) indicated short 10-year progression-free (P = 0.01 for ploidy and P = 0.0002 for SPF), overall (P = 0.004 and P less than 0.0001) as well as prostate cancer survival (P = 0.002 and P less than 0.0001). Ten-year overall survival rate was 45% in cases with SPF below 4.2% and 0% in those with higher values, whereas the corresponding prostate cancer-specific survival rates were 80% and 11%, respectively. None of the seven tumours with SPF above 12% showed an objective response to endocrine therapy, whereas 26/49 (52%) of those with lower SPF values responded (P = 0.01). DNA ploidy, tumour grade, T-stage or M-stage did not significantly correlate with endocrine responsiveness. SPF was also the best predictor of progression free survival in patients treated hormonally. In conclusion, detection of high SPF in prostate cancer may indicate lack of hormonal responsiveness and poor prognosis. PMID- 1911202 TI - Outcome in stage III non-Hodgkin's lymphoma in children (UKCCSG study NHL 86)- how much treatment is needed? United Kingdom Children's Cancer Study Group. AB - Forty-four children aged 3-13 years with Murphy stage III B cell non-Hodgkin's lymphoma were treated between May 1986 and December 1989. All have been followed up for at least 12 months. The primary site was the abdomen in 37 children, 24 of whom had involvement of other organs or nodal disease outside the abdomen. Twenty eight received a standard dose regimen (regimen 1) and 16 had a more intensive regimen (regimen 2--MACHO). Fourteen patients (87%) who received MACHO had extensive multi-organ disease compared to 15 (53%) on regimen 1. Most of the latter had only pleural effusions. Thirty-four children are alive relapse free and considering the early relapse pattern in this disease are probably cured (actuarial event free survival = 76%). There has been one relapse (6%) after MACHO, but three toxic deaths. Six patients (21%) on the less intensive regimen have relapsed. Morbidity was high in terms of infection and need for haematological support and hospitalisation in the one third of children electively given the more intensive regimen. It is concluded that the vast majority of children with stage III disease who have disease limited to lymph nodes are curable with a moderately intensive regimen. Those with multiorgan involvement probably require more intensive treatment. It is therefore of importance to clarify prognostic factors in these patients to determine who can be cured with a less intensive regimen and who requires further dose intensification. PMID- 1911203 TI - Histological features, DNA content and prognosis of breast carcinoma found incidentally or in screening. AB - Histology features, the nuclear DNA content and prognosis of 42 female breast carcinomas found in a physical examination based screening, 54 breast cancers found incidentally by medical personnel, and 274 breast cancers first suspected by the patient were compared. There was no significant difference in the distribution by primary tumour size (P = 0.08) or histological type (P = 0.87) of breast cancer between the screen-detected and 139 self-suspected cancers of women with similar mean age and living at the same time in the same city, but the screen-detected carcinomas were better differentiated (P = 0.0002), and had less mitoses (P = 0.008), less tumour necrosis (P = 0.004) and DNA aneuploidy (P = 0.01), smaller S-phase fractions (P = 0.009), less axillary metastases (P = 0.04), and had better outcome (P = 0.005) than self-suspected carcinomas. These parameters did not differ significantly between the screen-detected and incidentally found cancers, but incidental cancers had more often axillary metastases (P = 0.02). The results indicate that screen-detected breast carcinomas have favourable biological features suggesting low degree of malignant potential. PMID- 1911204 TI - A phase II clinical and pharmacokinetic study of Lonidamine in patients with advanced breast cancer. AB - Lonidamine is a substituted indazole carboxylic acid with a unique mechanism of action and early clinical studies have reported anti-tumour activity. In a phase II study 32 patients with previously treated advanced breast cancer were given Lonidamine in a daily divided oral dose of 600 mg. Of 28 patients evaluable for response, three (11%) achieved a partial response (4-24+ months) and three (11%) a minor response. Two patients have stable disease (greater than 3 months) and 20 progressed. Toxicity was very mild. Sixteen (53%) of 31 patients had myalgia which lasted a median of 2 weeks. This was investigated with nuclear magnetic resonance spectroscopy in four patients but the changes were unrelated to the degree of myalgia. No other major side-effect was seen, and no dose reduction was required. Lonidamine pharmacokinetics have been investigated in 17 patients 1 month after the start of therapy. Lonidamine was detected in the plasma of all patients, but there was no clear relationship between Lonidamine levels and clinical response or toxicity. Lonidamine appears to be active against advanced breast cancer and its low toxicity would allow combination studies with chemotherapy. PMID- 1911205 TI - The relationship between risk of death from clinical stage 1 cutaneous melanoma and thickness of primary tumour: no evidence for steps in risk. Scottish Melanoma Group. AB - Previous reports have suggested that the relationship between survival and thickness of primary cutaneous malignant melanoma is not linear, but that there are natural breakpoints at which survival worsens in a step fashion. Nine hundred and ninety-seven cases of primary cutaneous malignant melanoma less than 9.75 mm thick, excised in Scotland between 1979 and 1983 inclusive, were examined to see if this could be confirmed. An adjusted Cox's regression analysis showed that age, sex, site and thickness were all significant predictors of survival. Thickness was grouped either empirically or by the breakpoints reported by other authors. It was then entered into a model either as a regressor or as a factored variable. The ranges 0-9.75 mm and 0-2 mm were studied separately. In the 0-9.75 mm range the factored variable was a statistically significant better fit than the regressor for each set of breakpoints, including an empirical analysis with eight groups. This suggests that there is no single best fit and that a step effect is unlikely. Across the 0-2 mm range there was no significant improvement in the fit if thickness was entered as a factored variable, again indicating that a step effect is unlikely. We argue that there is no biological or statistical evidence to support the existence of natural breakpoints. PMID- 1911206 TI - A less toxic regimen of 5-fluorouracil and high-dose folinic acid for advanced gastrointestinal adenocarcinomas. AB - The combination of high-dose folinic acid with 5-fluorouracil has shown improved response rates in several trials in advanced colorectal carcinoma. This however is at the expense of increased toxicity: regimens using weekly bolus injections produce diarrhoea in most patients and occasional toxic deaths from this, whilst those using daily injections for one week in four report both diarrhoea and severe oral mucositis. Both types of regimen have significant rates of myelosuppression. A recent report described a different schedule of 5 fluorouracil and folinic acid, which appeared better tolerated but equally active (De Gramont et al., 1988). Here we report results using the same programme, in 64 patients with advanced adenocarcinomas. (Forty three colorectal, ten gastric, six pancreatic and five of unknown primary.) Patients received 200 mg m-2 folinic acid by infusion over 2 h followed by an IV bolus of 5-fluorouracil 400 mg m-2 then an infusion of 5-fluorouracil 400 mg m-2 over 22 h. This was repeated over the next 24 h. The schedule was given every 2 weeks for a total of six to 12 courses depending upon the response. The overall response rate was 26% in 62 evaluable patients. No toxicity greater than WHO Grade II occurred. Diarrhoea and mucositis did occur in around 10% of treatments but were not troublesome. No febrile neutropenic episodes were seen. Despite previous reports which described only modest activity for this combination against stomach cancers, this regimen demonstrates low toxicity but retains good activity in the palliative treatment of both gastric and colonic adenocarcinomas. PMID- 1911207 TI - Compliance with follow-up of patients treated for non-seminomatous testicular cancer. AB - Many patients with Stage 1 non-seminomas are now treated by orchidectomy and close follow-up along. Chart review indicated that a group of such patients, compared with patients treated with chemotherapy, tended to be less compliant with follow-up. A questionnaire given to a second sample of patients confirmed that surgical patients underestimated the dangers of the disease and chances of relapse, and doubted the value of follow-up. PMID- 1911208 TI - Season of detection of breast cancer. PMID- 1911209 TI - Epithelial ovarian cancer: a cytokine propelled disease? PMID- 1911210 TI - Systemic immunotoxin therapy of cancer: advances and prospects. PMID- 1911211 TI - Tumour progression and the nature of cancer. AB - The nature of neoplasia and its sometime end result, cancer, has been studied by exposition and explanation of the sequential lesions of tumour progression. Neoplastic lesions were divided into four classes on the basis of growth characteristics and whether lesional growth is confined to one or more tissue compartments. Class IA, the initial lesion, an orderly, probably clonal growth, usually differentiates and disappears. Class IB: Failure to differentiate accompanied by disorderly growth. Class IC: Randomly dispersed atypical cells, constituting a precursor state. Class II, intermediate lesions, apparently arising from the atypical cells, show temporally unrestricted growth within the tissue compartment of origin. Class III lesions, primary invasive cancers, show temporally unrestricted growth in two or more tissue compartments and metastasise along different paths, a property associated with extracellular matrix interaction. The metastatic pathways may result from different subsets of cells in the primary cancer. Class IV lesions are the metastases. It was concluded that, all neoplasms develop in the same way, have the same general behavioural characteristics, and, when malignant, all interact with the extracellular matrix of the primary and the secondary sites. The origins and development of cancer are considered to be pluralistic and not due to a discrete change in a cell, whose progeny, as a result of that discrete change, carries all of the information required to explain the almost limitless events of a neoplastic system. PMID- 1911212 TI - XH1--a new cervical carcinoma cell line and xenograft model of tumour invasion, 'metastasis' and regression. AB - A new cell line, XH1, has been derived from an invasive focally keratinising adenosquamous carcinoma of the cervix in a 32 year old patient. It has been maintained in long term monolayer culture for 26 months, and passaged over 100 times (much greater than 300 population doublings). It is aneuploid with a mean chromosome number of 78. Examination using two minisatellite hypervariable DNA probes has shown it to be different from other cell lines maintained in this laboratory and from HeLa. Two sublines, XH1a and XH1b, show marked differences in monolayer culture, growth in soft agar, and xenograft formation. XH1 and XH1a cells readily form subcutaneous xenografts, and lung colonies can be established by their intravenous injection. Subcutaneous injection of XH1b cells results in rapid cell growth for a few days after which the tumour undergoes degeneration and then regresses completely. The XH1 karyotype has many rearranged chromosomes. Parental XH1 cells and both sublines show integration of HPV16 into the genome. PMID- 1911213 TI - The effect of ricin B chain on the intracellular trafficking of an A chain immunotoxin. AB - Covalent linkage of the A chain of ricin to the LICR-LOND-Fib75 monoclonal antibody produced an immunotoxin, Fib75-SS-ricin A, which demonstrated immunospecific toxicity to human bladder carcinoma cells in tissue culture (Forrester et al., 1984). The present studies have shown that ricin B chain potentiates the toxicity of the immunotoxin by two orders of magnitude and also significantly increases the rate of protein synthesis inhibition. Using immunoelectron microscopy, the receptor-mediated endocytosis and intracellular routing of the immunotoxin was studied with and without ricin B chain treatment after immunolocalisation of the conjugate. Fib75-SS-ricin A was internalised by the EJ cells predominantly in uncoated pits and vesicles and directed to the endosomes. Some degradation of the complex appeared to take place in multivesicular endosomes at early timepoints and 24 h after internalisation, most of the immunotoxin was found in lysosomes. Some ricin A chain epitopes were detected in Golgi vesicles. Cells treated with immunotoxin and ricin B chain endocytosed the complex predominantly in coated pits and coated vesicles. Using pre-embedding immunoperoxidase techniques, ricin chains were found in the whole Golgi complex and most of the conjugate escaped lysosomal degradation. Internalised immunotoxin was recycled back to the plasma membrane in an active form associated with vesicles which appeared to be derived predominantly from multivesicular endosomes. A similar mode of recycling has recently been reported (McIntosh et al., 1990) for ricin holotoxin in the same cell line. These observations may explain the potentiating effect of toxin B chains in the antibody-directed targeting of toxin A chains. PMID- 1911214 TI - Glucose starvation and acidosis: effect on experimental metastatic potential, DNA content and MTX resistance of murine tumour cells. AB - Exposure to oxygen deprivation in vitro has been reported to cause drug resistance in CHO cells (Rice et al., 1986; PNAS 83, 5978) and enhancement of experimental metastatic (colonisation) ability of murine tumour cells (Young et al., 1988; PNAS 85, 9533). Both these studies also demonstrated the induction of a subpopulation of cells with excess DNA content. Since the micromilieu in tumours results in exposure of the tumour cells to conditions of acid pH and nutrient deprivation, as well as hypoxia, we have examined the effect of exposure to acidosis (pH 6.5) and glucose starvation on drug resistance, cellular DNA content and the experimental metastatic ability of KHT sarcoma and B16F1 melanoma cells. Cells were exposed to these conditions for 24 and 48 h and tested for resistance to methotrexate (MTX) or experimental metastatic ability either immediately following these exposures or after 24 or 48 h of recovery in normal growth medium. Both cell lines demonstrated an enhancement of colonisation potential, which was most marked when cells were injected after 48 h of exposure followed by a 24 or 48 h recovery period. Flow cytometric analysis demonstrated an increase in the fraction of KHT cells with excess DNA following both glucose starvation and acidosis we observed only a small increase in MTX resistance following acidic exposure of cells and no change following glucose starvation. Since both acidosis and glucose starvation are known to induce glucose regulated proteins (grp), a subset of the stress protein family, we studied the effect of treatment with another known inducer, 2-deoxyglucose. We found that this agent affected the metastatic efficiency of KHT cells in a manner similar to that observed following exposure to glucose starvation and acidosis. However, further studies are required to establish what role, if any, grp play in this effect. In conclusion this study shows that transient exposure of murine tumour cells to an acidic or glucose deprived environment can cause progression in terms of metastatic potential. PMID- 1911215 TI - Phorbol ester and bryostatin effects on growth and the expression of oestrogen responsive and TGF-beta 1 genes in breast tumour cells. AB - The phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA) (10 nM) produce a marked reduction in the growth, measured by thymidine uptake, of MCF-7 cells in full growth medium, but had only a small effect on MDA-MB-231 and T47D cells. Bryostatin alone also inhibited growth but to a lesser extent than seen with TPA. The effect of TPA on MCF-7 cells was partially reversed by bryostatin, added simultaneously or after TPA, suggesting bryostatin does not simply mimic TPA in this system. Even though both are believed to act via effects on protein kinase C, bryostatin appears to act as antagonist to the effect of TPA as well as a partial agonist on its own. When the oestrogen receptor positive MCF-7 and T47D cells were maintained in charcoal stripped serum, the increase in DNA synthesis on stimulation with oestradiol was inhibited with 50 nM TPA in MCF-7 cells but not in T47D cells. The effects of these treatments on the expression of two well characterised oestrogen responsive genes pNR2(pS2) and pNR100 (Cathepsin-D) were examined. Rather than preventing transcription of these oestrogen responsive genes, TPA alone increased pNR2 and pNR100 levels in MCF-7 cells and the combined effect of oestradiol and TPA had a marked synergistic effect in increasing the transcript levels of these genes. In T47D cells pNR2 transcripts were not detected and the increase in pNR100 mRNA levels were not affected by TPA. We conclude that the inhibitory effects of TPA on the growth stimulation of MCF-7 cells by oestradiol was not due to a general inhibition of the expression of oestrogen responsive genes. An alternative possibility examined was that the growth inhibitory effect of TPA on MCF-7 cells might be due to stimulation of TGF beta 1, acting as an autocrine inhibitory growth factor. Oestradiol treatment of MCF-7 cells reduced the levels of TGF-beta 1 mRNA whereas TPA produced a marked increase. The combined effect of TPA and oestradiol further increased TGF-beta 1 mRNA above the levels seen with TPA alone. Bryostatin had little effect on TGF beta 1 expression either alone or in combination with oestradiol. These observations are consistent with the hypothesis that the inhibitory effect of TPA on MCF-7 cells may be partly due to autocrine inhibition by TGF-beta 1. PMID- 1911216 TI - Expression of the pNR-2/pS2 protein in diverse human epithelial tumours. AB - The pNR-2/pS2 protein is regulated by oestrogens in breast cancer cell lines. This report describes a systematic survey of pNR-2/pS2 expression in a number of common epithelial tumours. Expression was evaluated immunohistochemically in an archival series using antisera raised against the C-terminus of the pNR-2/pS2 protein. Expression of pNR-2/pS2 by malignant epithelial tumours was widespread. Intense immunohistochemical staining was found in tumour cells in a proportion of pancreatic (6/8), large intestinal (7/12), gastric (9/16) and endometrial (4/12) carcinomas. Positive staining for the pNR-2/pS2 protein was also found in both benign and malignant ovarian epithelial tumours and was very significantly associated with mucinous differentiation (P less than 0.00001). Small numbers of carcinomas of bladder (2/10) and prostate (2/7) showed less intense staining and single examples of cervical carcinoma (1/7) and lung carcinoma (1/19) stained positively. None of the renal carcinomas (0/16) examined stained positively. Positive staining showed no correlation with gender. Although there are reports of oestrogen receptor expression in most of the tumour types considered, the possibility of other regulatory influences must also be considered. The pNR-2/pS2 protein may well have a more general role in human epithelial neoplasia than hitherto realised. PMID- 1911217 TI - The potential for prazosin and calcitonin gene-related peptide (CGRP) in causing hypoxia in tumours. AB - Using 31P NMR spectroscopy, changes in tumour metabolic status were studied in a transplanted rat fibrosarcoma following the administration of vasodilators. Mean Arterial Blood Pressure (MABP) was monitored simultaneously. Two vasodilators were studied, prazosin and CGRP, which altered the NMR parameters Pi/sigma P, beta NTP,Pi, PCr/Pi and PME/Pi in a dose dependent manner. There was a good correlation between the various NMR parameters; for analysis, Pi/sigma P was used for convenience. With increasing doses of vasodilator, Pi/sigma P increased and the MABP decreased. Reduction in pHNMR showed a correlation with decreasing MABP following the administration of prazosin but not after CGRP. Both prazosin and CGRP produced changes in 31P NMR spectra consistent with a reduction in tumour blood flow. The results for prazosin and CGRP were comparable and showed a 15-20% increase in Pi/sigma P for a 20% reduction in MABP. These results were compared with those from hydralazine. With hydralazine an acceptable reduction in blood pressure (up to approximately 25%) has little effect and may even alter NMR parameters consistent with an increase in blood flow, a reduction of approximately 40% is required for a significant decrease in flow. Both prazosin and CGRP are shown to be far more effective than hydralazine in causing tumour hypoxia at a clinically acceptable reduction in blood pressure. CGRP may be the more suitable for clinical use because of its short half life, its capability to achieve controlled hypotension and the relatively few side effects associated with its use. PMID- 1911218 TI - Anticoagulant treatment does not affect the action of flavone acetic acid in tumour-bearing mice. AB - Flavone acetic acid (FAA) is a novel antitumour agent that has a profound effect on the vasculature in murine tumour models. Previously we have shown that FAA induces a coagulopathy and thrombocytopaenia in tumour-bearing mice, and the purpose of the present study was to determine the significance of the FAA-induced intravascular coagulation in the antitumour action of FAA. Several anticoagulant agents were tested for their effectiveness in altering ex vivo coagulation of murine plasma; heparin and ancrod were found to be most effective. These agents were administered to tumour-bearing mice prior to FAA and TNF treatment with little effect on the induced regrowth delay. However: the FAA-induced consumption of platelets in tumour-bearing mice was not blocked by anticoagulant treatment. These data suggest that platelet consumption occurs independently of the normal coagulation pathway, and further that fibrin deposition may not be a major factor in the antitumour action of FAA. PMID- 1911219 TI - Establishment and characterisation of human carcinoembryonic antigen transgenic mice. AB - We have produced human CEA transgenic mice which were found to express CEA mRNA in all tissues. By immunoblot analysis using anti-CEA polyclonal antibody, we also detected CEA protein in all tissues. However, the molecular size of CEA in the brain was different from that in other tissues, although the mRNA size was same and no deletion nor rearrangement was detected at the DNA level. Immunohistochemical analysis of the lung and the colon showed that the expression sites were the bronchial epithelial cells of the lung and the columnar epithelial cells of the colon. Interestingly, the expression of CEA protein in the transgenic mice was polarised to the luminal side of epithelial cells similar to the normal CEA expression in human tissues. We also detected cell surface expression of human CEA on thymocytes and spleen cells and CEA expression was greatly reduced by the phosphatidylinositol-specific phospholipase C (PI-PLC) treatment. PMID- 1911221 TI - Hodgkin's disease mortality in Europe. AB - Trends in mortality from Hodgkin's disease between mid 1950s and the late 1980s have been analysed for 16 western European and seven eastern European countries. In all western countries there were substantial falls in mortality from the late 1960s onwards, for an overall mean decline of 50% in both sexes, although these falls were somewhat larger in Nordic countries (approaching 70% in Denmark and Sweden), and more limited (20 to 30%) in Portugal, Spain and Greece. The reductions in Hodgkin's disease mortality were evident both in younger (under 35) and middle age (35 to 64 years), as well as in children under 15 and, in several countries, in the elderly (above 65), too. They were persistent up to the most recent calendar periods, with no evidence of flattening off. The pattern of trends in Hodgkin's disease mortality was largely different in Eastern Europe. Among seven countries examined, some fall was observed only in Bulgaria and Czechoslovakia, but other countries showed no consistent pattern and there was some increase, too. In absolute terms, the reductions in Hodgkin's disease mortality in Western Europe correspond to the avoidance of over 3,000 deaths per year. This stresses the importance and urgency of improving the availability of currently defined knowledge and resources for treatment of Hodgkin's disease in Eastern Europe. PMID- 1911220 TI - BW12C: effects on tumour hypoxia, tumour thermosensitivity and relative tumour and normal tissue perfusion in C3H mice. AB - BW12C (5-[2-formyl-3-hydroxypenoxyl] pentanoic acid) is an agent which stabilises oxyhaemoglobin and thus reduces oxygen delivery to tissues. It is of interest as a possible potentiator of bioreductive agents and/or hyperthermia. The increases in radiobiological hypoxic fraction of RIF-1 and KHT tumours 30 min after 70 mg kg-1 BW12C i.v. were measured and shown to be similar; factors (+/- 2 s.e.) ranged from 3.87 (2.84-5.29) to 5.92 (1.92-18.2) despite the large variation in initial hypoxic fraction, from 0.30 (0.18-0.50) % for RIF-1 intramuscularly in the leg to 16.3 (14.7-18.1) % for subcutaneous KHT flank tumours. Thermosensitivity of intramuscular KHT leg tumours was not enhanced by 70 mg kg-1 BW12C 30 min before heating at 43 degrees C, 43.5 degrees C or 44 degrees C, assayed by regrowth delay. The effect of 70 mg kg-1 BW12C on relative tissue perfusion (RTP), assayed by 86Rb extraction, was measured from 0.5 h to 6 h after treatment. After 1 h RTP (+/- 2 s.e.) in RIF-1 tumours was reduced to 84 +/- 5.7% and 68 +/- 9.6% of control in leg and flank tumours respectively, and to 86 +/- 6.4% in leg muscle while flank skin RTP was unaltered at 109 +/- 8.6%. There were substantial increases in kidney (149 +/- 10.7%) spleen (173 +/- 22.1%) and lung (128 +/- 10.4%) at 1 h but in liver there was a decrease at 2 h to 85 +/- 8.4%. Dose response studies showed that the threshold dose for reduction of tumour RTP is between 55 and 70 mg kg-1, but perturbations in normal tissue RTP occur at lower doses, e.g. 40 mg kg-1 for spleen. BW12C had minimal effects on renal function measured by 51CrEDTA clearance. The data as a whole indicate that reduction in tumour perfusion is likely to be an important determinant in the increase in tumour hypoxia induced by BW12C. PMID- 1911222 TI - Radiation effects on uptake of 99Tcm-hexamethylpropylen amine oxime (HMPAO) in head and neck tumours. AB - Twenty patients with malignant head and neck tumours were imaged with 99Tcm labelled hexamethylpropylene amine oxime (HMPAO), a radiopharmaceutical generally used for blood flow studies. Before radiotherapy (RT), 93% of the tumours could be detected with single photon emission computed tomography (SPECT) and 45% with planar imaging. Whole tumour-to-background 99TcmHMPAO uptake ratios ranged from 3.6 to 1.0 (mean 1.7 +/- 0.6) in untreated tumours. There was a good correlation between tumour volume and uptake (r = 0.69, P = 0.002). Sixteen patients were reimaged during or shortly after radical RT. 99TcmHMPAO uptake was significantly lower after treatment (mean uptake ratio 1.2 +/- 0.3, P less than 0.001). However, RT associated changes in 99TcmHMPAO uptake were in agreement with the clinical response in only 63% of the studies. This study indicates that 99TcmHMPAO SPECT imaging can be used for pretherapeutic localisation of head and neck tumours. Although most tumours show a decrease in uptake after irradiation the poor association with tumour regression does not allow for reliable assessment of treatment response. PMID- 1911223 TI - Immunocytochemical demonstration of PTHrP protein in neoplastic tissue of HTLV-1 positive human adult T cell leukaemia/lymphoma: implications for the mechanism of hypercalcaemia. AB - The infiltrated tissues from seven West Indian patients with HTLV-1 positive adult T cell lymphoma/leukaemia (ATLL) have been analysed by immunocytochemical techniques for the presence of immunoreactive parathyroid hormone-related protein (PTHrP), a hormonal mediator of humoral hypercalcaemia of malignancy. Six of the seven were hypercalcaemic at some stage of the course of their disease. Four of the six evaluable patients showed evidence of specific cellular and extracellular expression of PTHrP protein in neoplastic tissues. This finding suggests that PTHrP may be involved in the production of hypercalcaemia in at least some cases of T cell lymphoma - proof of a causal relationship however must await the demonstration of tissue release of PTHrP resulting in raised circulating hormone levels. PMID- 1911224 TI - DNA aneuploidy and low S-phase fraction as favourable prognostic signs in metastatic melanoma. AB - The prognostic value of cellular DNA content in melanoma metastases was investigated by flow cytometric analysis of fresh or paraffin-embedded tumour blocks from 95 consecutive patients referred to the Helsinki University Central Hospital Melanoma Team. Thirty-three per cent of the tumours were DNA diploid and 67% DNA aneuploid. S-phase fractions were lower in DNA diploid than in DNA aneuploid tumours (10.7% and 17.6%). Tumour ploidy and S-phase fraction were shown by multivariate Cox model analysis to be independent prognostic variables and major determinants of survival after first recurrence. Surprisingly, patients with DNA aneuploid tumours and with tumours with low SPF survived significantly longer than those with DNA diploid or high SPF tumours. This exceptional finding of favourable prognosis for DNA aneuploid tumours was more prominent among patients receiving intensive systemic therapy and among patients with stage IV disease, probably indicating a tendency for DNA aneuploid tumours to have higher sensitivity to systemic therapy. PMID- 1911225 TI - Association between the month of diagnosis and prognosis in breast carcinoma. AB - The effect of the month of diagnosis on survival was investigated in two series of unilateral invasive breast cancer, of which one comprised 95% of all such histologically diagnosed breast carcinomas in the city of Turku, Finland, in 1945 to 1965 (n = 401), and the other 94% of all such carcinomas diagnosed in 1980 to 1984 (n = 337). If the histological diagnosis was made in January, February, or August to October in 1945-65, or in July to September in 1980-84, mortality in breast cancer was greater than if the diagnosis was made during the rest of the year (P = 0.03 and 0.009, respectively). Cancers diagnosed during the unfavourable months had more tumour necrosis in both series, and higher mitotic count and larger tumour size in the 1945-65 series. The number of diagnosed cases was usually less than the median during the months associated with unfavourable prognosis. Hypotheses to explain the altering prognosis by the month of diagnosis include seasonal hormonal changes and social factors. PMID- 1911226 TI - Objective measurement of therapeutic response in breast cancer using tumour markers. AB - In 65 patients with systemic breast cancer, a biochemical response index using three tumour markers in combination, carcinoembryonic antigen (CEA), carbohydrate antigen 15-3 (CA 15-3) and erythrocyte sedimentation rate (ESR), allowed objective biochemical assessment of response to endocrine therapy. Changes in these three markers at 2, 4 and 6 months showed a highly significant correlation with UICC assessed response at 6 months. At 4 months, changes in these three markers resulted in a selectivity of 93%, with a sensitivity of 92% and a specificity of 82%. Survival of groups of patients assessed biochemically or by UICC criteria for non-progression or progression showed no significant difference. The advantage of the biochemical assessment are that it is objective and reproducible. The assessment gives similar information to the UICC assessment but can be carried out earlier. Changes in the three markers appears to reflect the dynamics of change in tumour mass in response to systemic therapy in contrast to the UICC criteria which reflect structural change. PMID- 1911227 TI - Influence of the antioestrogen tamoxifen on normal breast tissue. AB - Immunohistochemical assays have been employed to study the expression of ER, PgR, EGFR and Ki67 immunostaining in normal breast tissue (n = 76). The expression of ER and PgR was highly variable in both pre and postmenopausal women and was characterised by large numbers of apparently negative cells. This was most evident for ER-ICA staining in tissues removed from premenopausal women. PgR levels were highest in the ducts of premenopausal women, while EGFR expression was elevated in both ducts and lobules. Ki67 expression was observed in less than 10% of all normal cells and was suppressed by the menopause in lobular tissue. Tamoxifen therapy (40 mg d-1) did not influence the expression of PgR, EGFR or Ki67 immunostaining in cancer associated normal tissue (n = 17). A significant increase, however, was observed in the mean percentage ER positivity in ductal tissue. No effect of duration of tamoxifen therapy was observed on the expression of the antigens studied. PMID- 1911229 TI - Platinum and other metal coordination compounds in cancer chemotherapy. A commentary on the sixth international symposium: San Diego, California, 23-26th January 1991. AB - The use of molecular biological methodologies has provided a greater understanding of the cytotoxic effects of cisplatin and the underlying mechanisms of tumour cell resistance. Resistance to cisplatin is often multifocal with plasma membrane, cytosolic and nuclear components. Cisplatin-DNA adducts appear to be recognised by specific damage recognition proteins. Proteins associated with the transport of platinum through plasma membranes and genes associated with cisplatin resistance appear to be close to being elucidated. Current Phase I and Phase II clinical trials with platinum-containing complexes largely focus on the 1,2 diaminocyclohexane (DACH) carrier ligand, the dicarboxylatocyclobutane leaving group and complexes which circumvent cisplatin resistance in murine leukaemia models. At present, the trials are at too early a stage to allow comment on their clinical utility and, consequently, the relevance of the murine leukaemia-based preclinical observations. On the horizon, orally active platinum (IV) ammine/amine dicarboxylate dichloride coordination complexes with preclinical toxicological profiles similar to carboplatin should enter clinical trial in the next year. PMID- 1911228 TI - Intracellular magnesium concentrations and acute anthracycline-induced cardiotoxicity. PMID- 1911230 TI - CRC-BACR-AICR International Workshop. Melanogenesis: its chemistry as a therapeutic strategy in melanoma. PMID- 1911231 TI - Report of BACR workshop on monoclonal antibodies in breast and ovarian cancer, Brasenose College, Oxford March 17-19th 1991. PMID- 1911233 TI - First principles of magnetic resonance angiography. AB - For several years, magnetic resonance imaging (MRI) has shown promise as a noninvasive tool for the study of the vascular system. One interesting format, so called MR angiography, produces results resembling conventional x-ray angiographic images. This article lays a solid, rigorous foundation for an intuitive understanding of these effects without the use of advanced mathematical concepts. The current state of the art in data acquisition and postprocessing is illustrated. Finally, relevant hemodynamic concepts are introduced, in order to characterize the physiology of complex blood flow at bifurcations. MR angiography is particularly sensitive to artifacts associated with complex flow. The article ends with a call to investigate these phenomena, because they will directly affect the success of MR angiography as a technique. PMID- 1911232 TI - Kinematic magnetic resonance imaging of the joints: techniques and clinical applications. AB - Recently, kinematic magnetic resonance imaging (MRI) techniques have been developed to provide diagnostic information related to the functional aspects of the joints. The kinematic MRI evaluation of the joint is used to assess the various interactions of the soft tissues and bony anatomic structures that comprise the joint, and to evaluate the relative alignment of these structures through a specific range of motion. The use of kinematic MRI techniques for examination of the joints provides the radiologist and the clinician with augmented data of anatomic and movement-related information. PMID- 1911234 TI - Locomotor system assessment by muscle magnetic resonance imaging. AB - Clinical evaluation of the locomotor system has long been hampered by difficulty in assessing the morphologic and functional integrity of skeletal muscles. Diagnostic imaging represents a major advance in the diagnosis and management of patients with locomotor dysfunction through the possibility of probing beyond overlying soft tissues to identify muscle lesions, determine their extent, characterize their composition, direct invasive procedures, and monitor therapies. Magnetic resonance imaging (MRI) appears to be the most promising of available imaging methods, because of its great sensitivity to changes in muscle water distribution and fat content. Also, it can distinguish between individual deep and superficial muscles. Serial evaluations of many muscles are practical because of the safety of MRI. While the cost effectiveness in the workup of locomotor dysfunction remains to be determined, the scientific and practical clinical information now available merits further investigation by clinicians and radiologists alike. The purpose of this review is to describe the potential role of skeletal muscle MRI in evaluating the locomotor system. PMID- 1911235 TI - Equal opportunities: equal only on paper? PMID- 1911238 TI - Patient's Charter: help for health. PMID- 1911237 TI - Citizen's Charter: a welcome start. PMID- 1911236 TI - Nurses' homes: accommodation and the new regime. PMID- 1911239 TI - Elderly people: investigating the sundown syndrome. PMID- 1911240 TI - Computers in nursing: interactive video as a teaching medium. PMID- 1911241 TI - Promoting nursing research in India. PMID- 1911242 TI - Home self-infusion of i.v. immunoglobulin. PMID- 1911243 TI - 'Private therapists' who refuse to reveal whether they have any qualifications. PMID- 1911244 TI - Tradimus. Education: hurly-burly P2000. PMID- 1911245 TI - Tradimus. Travel: Calcutta's hope for a healthier future. PMID- 1911246 TI - Tradimus. Exams: bouncing back. PMID- 1911247 TI - Tradimus. Community advocate. Nursing Standard/Glaxo essay competition. PMID- 1911248 TI - Tradimus. Placements: more than skin deep. PMID- 1911249 TI - Tradimus. Student patients: shift those patterns. PMID- 1911251 TI - Health politics: friend or foe?. Interview by Daniel Allen. PMID- 1911252 TI - Northern Ireland focus. The same, but different. PMID- 1911250 TI - Tradimus. Student magazine: student scoop. PMID- 1911253 TI - The Clay column. Real power to the people. PMID- 1911255 TI - Caesarean section: psychosocial effects. PMID- 1911254 TI - Designing a diabetes specialist course. PMID- 1911256 TI - Women: unique HIV transmission risks. PMID- 1911257 TI - Sick building syndrome. PMID- 1911258 TI - Income generation: the generation game. PMID- 1911259 TI - Nursing practice: scrutinising the power complex. PMID- 1911260 TI - Whistleblowing: gagging the nurse. PMID- 1911261 TI - Ophthalmology. A revolving role? PMID- 1911262 TI - Ophthalmology. Beliefs about cataract. PMID- 1911263 TI - Ophthalmology. Screening for diabetic retinopathy. PMID- 1911265 TI - Northern Ireland focus. The diversity of nursing. PMID- 1911264 TI - Ophthalmology. Eye structure: a functional view. PMID- 1911266 TI - Infertility: assisted conception. PMID- 1911267 TI - Relief work: bizarre game of rugby. PMID- 1911268 TI - Characteristics of student cohorts. PMID- 1911269 TI - Skin bacteria: what is normal? PMID- 1911270 TI - Teaching nurses about managing pain. PMID- 1911271 TI - Interdisciplinary pain management. PMID- 1911272 TI - The specialist nurse in mental handicap. PMID- 1911273 TI - Working parents: nursery crimes. PMID- 1911274 TI - Reformation power. PMID- 1911275 TI - Primary nursing: in our prime? PMID- 1911276 TI - Politics: ten commitments. Interview by Derek Hand. PMID- 1911277 TI - NHS reforms: leaking the bad news. PMID- 1911278 TI - NHS reforms. Would you Trust the doctor's regime?. Interview by John Naish. PMID- 1911279 TI - The Clay column. Sore points. PMID- 1911280 TI - Women in politics: a feminist sold short. Interview by Linda Bailey. PMID- 1911281 TI - Continuing education in the United States. PMID- 1911282 TI - Genetic research into schizophrenia. PMID- 1911283 TI - Project 2000 courses and elderly people. PMID- 1911284 TI - Why do you work? PMID- 1911286 TI - Theatre nursing. Moving into Europe. PMID- 1911287 TI - Theatre nursing. Educational development. PMID- 1911285 TI - Practice nursing: losing the advantage. PMID- 1911288 TI - Theatre nursing. Back to the future. PMID- 1911289 TI - Theatre nursing. Patient visiting: an essential role. PMID- 1911290 TI - Theatre nursing. Defining an operational strategy. PMID- 1911291 TI - Identification of a group of children with dyslexia by means of IQ-achievement discrepancies. AB - The reading and spelling abilities of 462 school children of mean age 8 years 7 months were examined in relation to their intellectual abilities (as assessed by the WISC-R) by means of cluster analysis. The analysis identified five groups. In one group reading and spelling were considerably poorer than their intellectual abilities. The performance of the five groups was examined on a number of cognitive tests commonly associated with dyslexia. The group identified as having significant discrepancies showed the poorest performance on many of these tests. In addition this group showed other features associated with dyslexia. Further analysis indicated the existence of two subgroups which differed significantly in performance on the cognitive tests. PMID- 1911292 TI - Detection of a novel basement membrane antigen by GDA-J/F3 anti-human sperm fibrous sheath monoclonal antibody. AB - Basement membrane zones (BMZ) of human epithelia were stained with GDA-J/F3 monoclonal antibody, which was originally raised against sperm cells. Using indirect immunofluorescence and immunoperoxidase techniques, the antibody reacted with the BMZ of stratified squamous epithelia (skin and its appendages, tongue, lip, oesophagus and cervix). It also stained the BMZ of trachea, nasal ciliated mucosa, some mammary ducts of lactating and resting breast, amnion and ureter but failed to react with that of stomach, ileum, colon, rectum, kidney, liver, fallopian tube, lung or their blood vessels. In testes, the antibody did not react with the BMZ of the seminiferous tubules although the sperm tails were stained. Split-skin immunofluorescence and immunoelectron microscopy localized GDA-J/F3 antigen to the inferior border of the lamina densa of the BMZ. In human foetuses, the epidermally associated antigen was detected at an estimated gestational age of 9 weeks, and in the amnion at 15 weeks. The antibody reacted with tissues from monkey but not from mouse, rat, cow or pig suggesting the late appearance of the antigen during evolution. Although the GDA-J/F3 was difficult to characterize biochemically, its tissue distribution, ontogeny and ultrastructural localization suggests that this antigen may be a type VII collagen-associated protein, whose expression is altered in recessive dystrophic epidermolysis bullosa. This disease could represent abnormalities in type VII collagen structure, assembly, transport or interaction with associated proteins. PMID- 1911293 TI - Interleukin-5-induced granulocyte activation in atopic patients. AB - The effect of recombinant human and murine interleukin-5 (IL-5) on granulocytes was investigated in patients with atopic dermatitis (AD) and allergic rhinitis and compared with those from patients with plaque psoriasis and normal non-atopic controls. Granulocyte activation was measured as lucigenin-dependent chemiluminescence (CL) and release of eosinophil cationic protein (ECP) as well as by scanning- and transmission-electron microscopy (EM) and the ultrastructural detection of production of H2O2. A significant direct effect of both human and murine IL-5 on granulocyte oxidative metabolism could only be detected in those patients with AD and allergic rhinitis. Also, as compared to normal controls, significantly increased CL responses were observed in these patients with stimulation with other granulocyte-activating cytokines, particularly GM-CSF. In patients with psoriasis there was no significant increase in response to stimulation with TNF alpha, TNF beta or GM-CSF, but IL-5 induced slight but significant CL responses in the granulocytes. None of the cytokines tested significantly stimulated the release of ECP in any of the groups. Ultrastructural studies showed that stimulation with human as well as murine IL-5 produced significant morphological changes in both eosinophils and polymorphonuclear neutrophilic granulocytes from the patients with AD. Production of H2O2 was visualized at the luminal part of the intracytoplasmic vesicles of the granulocytes and at the points of contact between the cells. On morphometric analysis, almost all the polymorphonuclear neutrophils in the patients with AD appeared to be activated, whereas only some of these cells in the normal controls showed signs of activation. PMID- 1911294 TI - Measurement of human hair growth by optical microscopy and image analysis. AB - We have developed a quantitative method for measuring hair growth using optical microscopy and image analysis, and have used this to investigate the rate of growth in subjects with and without alopecia. The hairs were cut from an area 7-8 mm in diameter and 24 h and 72 h later, images of the areas were obtained using an optical microscope and were recorded on a video disc. Measurements of the regrowing hairs, placed parallel to the scalp using a glass slide attached to the front of the microscope, were made using the image analyser. In subjects with little or no baldness there was a clear difference between fast-growing hairs and resting or slow-growing hairs. However, in subjects with alopecia there was no such difference and the growth rate of all the hairs showed a continuous distribution. Using this method other parameters such as the number of hairs per unit area and hair diameter as well as grouping of the hairs could be measured. PMID- 1911295 TI - Decreased sweat-gland number and function in patients with alopecia areata. AB - In this study the number and function of sweat glands on the dorsum of the hand and foot were evaluated using a silastic imprint method. Twenty patients, 11 females and nine males with either alopecia areata, alopecia totalis, or alopecia universalis were included in the study. Patients showed a significant decrease in activated sweat-gland number and function compared to matched controls (P less than 0.001). There was no significant relationship between the degree of sweat gland dysfunction and extent of hair loss, concurrent illnesses, or treatment. These findings suggest that eccrine sweat-gland function is compromised in patients with alopecia areata. PMID- 1911296 TI - Phenytoin has little effect on in-vitro models of wound healing. AB - It has been reported that phenytoin induces gingival and connective tissue hyperplasia and may be of use in wound healing. In this study the effect of phenytoin on human epidermal keratinocytes and skin fibroblasts has been investigated in vitro. Cell cultures were exposed to increasing concentrations of phenytoin from 10(-9) to 10(-4) M in the presence of 1 and 10% serum supplemented medium. In addition the effect of phenytoin on epidermal cell migration (epiboly) has been investigated using organ culture of human skin. No stimulation of cell growth was observed, and only a mild toxicity affecting keratinocytes was seen at the highest concentrations. Similarly, no effect on epidermal cell migration in vitro was observed. The lack of a direct effect in vitro suggests that any in vivo effect was not the result of interaction between phenytoin and keratinocytes or fibroblasts but possibly due to indirect modulation via other cell types, such as inflammatory or lymphoreticular cells. PMID- 1911297 TI - Skin susceptibility in uninvolved skin of hand eczema patients and healthy controls. AB - Basic physiological characteristics were examined in the uninvolved skin of 39 patients with hand eczema and in 39 healthy controls. Susceptibility to sodium lauryl sulphate (SLS)-induced irritant dermatitis was evaluated by the application of a single 24-h SLS patch test to the upper arm. Transepidermal water loss (TEWL) was measured by an evaporimeter, skin thickness by ultrasound A scan, blood flow by laser-Doppler flowmetry and skin colour by a chroma meter using the L*a*b* system of the Commission Internationale de l'Eclairage (CIE). No difference in basal TEWL values was found between patients and controls. A decreased skin thickness was found in those with hand eczema as compared to the controls. The hand eczema patients had significantly increased L* and decreased b*-values compared to controls, indicating a more 'fair' skin. Susceptibility to SLS was increased only in patients with acute eczema, indicating that the presence of an active eczema increases the reactivity to irritants of distant uninvolved skin. PMID- 1911298 TI - Platelet and coagulation studies in Ehlers-Danlos syndrome. AB - Fifty-one patients with Ehlers-Danlos syndrome were investigated for abnormalities of platelets and coagulation. Thirty-eight were examined prospectively and 13 retrospectively. A bleeding history was taken from all patients; only four (8%) gave no history of a bruising or bleeding tendency. Nine patients (18%) had significant haemostatic abnormalities of whom four (8%) had a platelet release defect, three (6%) had a factor XI deficiency and two (4%) had a factor XIII deficiency. Additionally 16 patients (31%) had mild abnormalities of uncertain significance of whom four (8%) had prolonged bleeding times (three in association with platelet aggregation abnormalities), 13 (26%) had platelet aggregation abnormalities and two had a positive Hess test. Twenty-four patients (47%) had normal tests for haemostasis of whom 20 (39%) had a bleeding diathesis and four (8%) had no such tendency. Results were analysed according to the type of Ehlers-Danlos syndrome, but there was no pattern to the abnormalities. The high frequency of a bleeding tendency in Ehlers-Danlos patients with normal tests for haemostasis (83%) supports the conventional explanation for this clinical feature, that defects in the structural integrity of skin and blood vessels lead to easy bruising. PMID- 1911299 TI - Alopecia areata in children: response to treatment with diphencyprone. AB - Twelve children with extensive alopecia areata or alopecia totalis were treated with the contact allergen diphencyprone. The duration of treatment ranged from 5 months to 1 year. Eight of the 12 (67%) regrew scalp hair and in four (33%) there was a complete regrowth. Six months after treatment was discontinued three of the four children with complete regrowth maintained their hair, one had lost all the regrowth and a further child with patchy regrowth at the end of treatment subsequently regrew hair completely while off therapy. PMID- 1911300 TI - Dowling-Degos disease and Kitamura's reticulate acropigmentation: support for the concept of a single disease. AB - Dowling-Degos disease and Kitamura's reticulate acropigmentation are both rare disorders of pigmentation, which predominantly affect the flexures and the extremities, respectively. A small number of patients with features of both disorders have been described, suggesting that these clinical patterns may be different manifestations of the same disease. We present a further case to support this conclusion. PMID- 1911301 TI - Precocious puberty in a boy with a widespread linear epidermal naevus. AB - A 7-year-old boy with a systematized verrucous epidermal naevus, multiple pigmented naevocytic naevi and precocious puberty is described. The possible basis for this previously unreported association of abnormalities is discussed. PMID- 1911302 TI - Recurrent facial oedema associated with a silicone-rubber implant. PMID- 1911303 TI - Pseudoporphyria and sunbeds, a coincidence in identical twins? PMID- 1911304 TI - Hydrochloric acid treatment of HEp-2 cells for the detection of masked anticentromere antibody (ACA) PMID- 1911305 TI - Melasma: a mask of stress. PMID- 1911306 TI - Foam cells after treatment with hydrocolloid dressings. PMID- 1911307 TI - No association between cicatricial pemphigoid and malignant disease. PMID- 1911308 TI - Lichen planus of the nails with giant cells: lichen nitidus? PMID- 1911309 TI - The treatment of human ectoparasite infection. PMID- 1911310 TI - The DEBR rat: an animal model of human alopecia areata. AB - The Dundee experimental bald rat (DEBR) is reported as a model for human alopecia areata. Parallels with human alopecia areata were observed in relation to the gradual and patchy loss of hair and the penetration of both pelage and vibrissa follicles by mononuclear cells. In particular, the apparent disruption of the follicles within the precortical region of the epidermal component and consequent alterations of normal geometrical relationships between dermal and epidermal components relate directly to similar studies on human alopecia areata. In comparison with other previously described hypotrichotic rodent mutants, the DEBR rat exhibits a unique mechanism of hair loss which may provide important information regarding the pathomechanism of human alopecia areata. PMID- 1911311 TI - The antiphospholipid syndrome. Clinical correlations, cutaneous features, mechanism of thrombosis and treatment of patients with the lupus anticoagulant and anticardiolipin antibodies. PMID- 1911312 TI - The metabolism of fibroblasts from normal and fibrotic skin is inhibited by minoxidil in vitro. AB - The effects of minoxidil in vitro were studied using fibroblasts grown from the lesional skin of patients with lichen sclerosus et atrophicus, morphoea and from the skin of normal individuals. The proliferation of all fibroblast lines over 3 days was inhibited in proportion to the concentration of minoxidil, being 20% or less of controls at 1 mM, where cell viability was only marginally reduced (84 +/ 2% vs. 88 +/- 2% (SEM) in controls). At 5 mM there was usually a net loss of cells and only 72% of those remaining were viable. In contrast, minoxidil at 0.1 1 mM stimulated the proliferation of foreskin keratinocytes by up to 130%. Contraction of collagen lattices containing the three types of fibroblasts was inhibited by 22-26% with 1 mM minoxidil after 5 days and by 50-94% with 5 mM. Secretion of glycosaminoglycans by normal fibroblasts showed concentration dependent reduction, being 25 +/- 6% of that of untreated cultures with 1 mM minoxidil. These findings show that minoxidil has a range of inhibitory effects on both normal and abnormal skin fibroblasts in vitro, which contrast with its stimulation of skin epithelial cells, and support suggestions that it may provide a useful topical treatment for keloids and other fibroses. PMID- 1911313 TI - Ultraviolet light induction of peripheral granulocytosis with splenomegaly: protection of mice with topical p-aminobenzoic acid (PABA). AB - Hairless mice were exposed to UVB irradiation from a Philips T1 12 light source. Mice that were exposed to UV-light and not protected with 5% p-aminobenzoic acid (PABA) showed a significantly higher number of peripheral blood granulocytes (P less than 0.001) and a significantly higher mean weight of both the spleen and the liver (P less than 0.001) than the non-irradiated controls. Light microscopy of the histology of the enlarged liver and spleen showed a proliferation of granulocytes and the reticuloendothelial cells. Treatment with topical PABA during the whole period of UV-exposure prevented the peripheral blood granulocytosis. These protected mice also had a significantly (P less than 0.001) lower mean weight for the liver and spleen than UV-exposed and non-protected mice. PMID- 1911314 TI - IgE antibodies to Pityrosporum ovale in atopic dermatitis. AB - An enzyme-linked immunosorbent assay (ELISA) was developed to assess serum IgE antibodies directed against Pityrosporum ovale in patients with atopic dermatitis (AD), atopic patients with allergic respiratory disease (ARD: rhinitis or asthma) but without eczema, and in healthy controls. IgE binding to P. ovale extract was demonstrated in 49% (35/72) of AD patients. In contrast, anti-P. ovale IgE was found in only one of 27 atopic controls without eczema; all healthy control sera (n = 17) were negative. Of 37 AD patients tested intracutaneously with P. ovale, 31 showed immediate-type reactivity, and 20 of these 31 patients had anti-P. ovale IgE detectable by ELISA, while sera from the six non-responders were all negative. Levels of anti-P. ovale IgE were highest in AD patients aged 20-30 years. No correlation was found with the severity of AD, but there was a non significant tendency (P = 0.06) to higher levels in AD patients with concomittant respiratory allergy. Anti-P. ovale IgE was significantly correlated with total serum IgE, with specific IgE against various aeroallergens as measured by RAST, and with levels of anti-Candida albicans IgE, measured with a similar ELISA. Thus, production of IgE antibodies against P. ovale occurs very frequently in AD, and rarely in patients with atopic disease without skin involvement. PMID- 1911315 TI - Ultrastructural localization of pemphigus vulgaris and pemphigus foliaceus antigens in cultured human squamous carcinoma cells. AB - The ultrastructural localization of the pemphigus vulgaris (PV) and pemphigus foliaceus (PF) antigens in cultured human squamous carcinoma cells was observed using immunogold electron microscopy. Both the PV and PF autoantibodies bound only to the extracellular portion of the desmosomal structures. After incubation at 37 degrees C, the PV antigen-antibody complexes were observed within the cultured cells. PV and PF antigen expression was markedly reduced when the cells were cultured in medium with a low Ca2+ concentration. PMID- 1911317 TI - Psychological characteristics of women with androgenetic alopecia: a controlled study. AB - The psychological characteristics and the hair problems of 58 females with androgenetic alopecia were compared with a group of women with non-apparent dermatological diseases, and with a group of men with androgenetic alopecia. The women with androgenetic alopecia had higher scores for self-sufficiency and social inadequacy compared to women with non-visible dermatological complaints, and they scored higher for inadequacy, rigidity and general psychological maladjustment than the men and had lower scores for injuredness self-evaluation and self-esteem. The women with androgenetic alopecia had more psychosocial problems, which they attributed to the hair loss, than the other groups. PMID- 1911316 TI - The influence of cutaneous factors on the transcutaneous pO2 and pCO2 at various body sites. AB - The transcutaneous partial pressures of oxygen (tcpO2) and carbon dioxide (tcpCO2) were measured at eight different sites in 10 adult male subjects with an electrode at a temperature of 44 degrees C. The mean tcpO2 values (mmHg) were significantly lower on the face (forehead 26.6, cheek 29.6) and the palm (26.4) than at other sites (60.6-69.6). The tcpCO2 values (mmHg) were only slightly higher on the face. Removal of the stratum corneum produced an average increase of the tcpO2 on the palm of 37.6 mmHg and on the forehead of 19.6 mmHg. However, in 10 children with an age range of 3-9 years, the difference in the mean pO2 between the cheek and forearm was very small. There was no significant difference in the cutaneous blood flow at 44 degrees C between the cheek, palm and forearm. PMID- 1911318 TI - The effect of oral indomethacin on psoriasis treated with the Ingram regime. AB - Fifty patients with psoriasis undergoing a standard Ingram regime were entered into a double-blind comparison of oral indomethacin and placebo. No significant differences were observed between the two groups in respect of disease activity or dithranol tolerance after 6 weeks. PMID- 1911319 TI - Successful 2-week treatment with terbinafine (Lamisil) for moccasin tinea pedis and tinea manuum. AB - A new orally active antifungal agent, terbinafine, was used in the treatment of tinea pedis ('dry type' or moccasin type) and tinea manuum. Fifty-three adults over the age of 16 years with fungal infections of the feet and/or hands were treated with either oral terbinafine, 250 mg, or placebo, once daily for 2 weeks. The diagnosis of fungal infection was confirmed by examination of skin scrapings by microscopy and culture. Of these, 28 patients were evaluable for efficacy. At 8 weeks, 12 out of 14 (86%) patients who received terbinafine were mycologically negative (microscopy and culture) compared to one out of 14 (7%) patients on placebo (P less than 0.001, Fishers exact test, one-sided). At the end of the study 71% of patients in the terbinafine group were judged to have received effective therapy compared to 0% in the placebo group (P less than 0.001). Terbinafine was well tolerated, and more side-effects were seen in the placebo group. PMID- 1911321 TI - Long-term survival and preservation of natural killer cell activity in a xeroderma pigmentosum patient with spontaneous regression and multiple deposits of malignant melanoma. AB - A 67-year-old man with xeroderma pigmentosum (XP) originally presented with malignant melanoma at the age of 28 years. This recurred 22 years later and subsequently numerous primary and secondary melanomas developed on the skin, several of which underwent spontaneous regression. Despite a marked lymphopenia, the proportion of natural killer cells was elevated and it is proposed that this led to the regression of the melanomas. Skin-derived fibroblasts from the patient were more sensitive to UVC (D10 approximately 3 J/m-2) than those from normal individuals (D10 approximately 15 J/m-2). The fibroblast culture was shown to be defective in excision repair with less than 10% of residual activity compared with controls. No assignment to a complementation group has yet been made. There was an elevated frequency of mutants resistant to 6-thioguanine in the circulating T lymphocytes. PMID- 1911322 TI - Rothmund-Thomson syndrome. PMID- 1911320 TI - Lichen planus pemphigoides: its relationship to bullous pemphigoid. AB - Clinical and immunopathological studies of three patients with lichen planus pemphigoides (LPP) were carried out to investigate the relationship between LPP and bullous pemphigoid (BP) and to determine whether the antigen in LPP is the classical BP antigen. LPP is usually considered to be the coexistence of lichen planus with BP. The bullae in LPP were subepidermal and indistinguishable from BP. Indirect immunofluorescence demonstrated antibody binding to the epidermal surface of 1 M NaCl-split skin and mucosae, as in BP. The tissue distribution of the LPP antigen mirrored the distribution of BP in stratified squamous epithelia but was absent from transitional epithelia (pig bladder). Immunoelectron microscopy, both direct (two cases) and indirect (one case), showed binding to the lamina lucida as with BP antigen. Western blotting of epidermal extracts using the patients' sera showed that instead of reacting with the classical bullous pemphigoid antigen (220 kDa in our series), the antisera reacted with a unique band of 200 kDa in addition to the band of 180 kDa found as a minor antigen in bullous pemphigoid, but more commonly in pemphigoid gestationis. The relationship between these antigens awaits molecular characterization. These findings suggest that the target antigen in LPP may be unique. PMID- 1911323 TI - Proceedings of the 255th meeting of the Netherlands Society for Dermatology and Venereology, Utrecht, 2 February 1991. PMID- 1911324 TI - Type I allergy to latex. PMID- 1911325 TI - Incontinentia pigmenti (Bloch-Sulzberger). PMID- 1911326 TI - Relapsing polychondritis. PMID- 1911327 TI - Unexplained myalgia in a patient with linear IgA disease. PMID- 1911328 TI - Treatment of pyoderma gangrenosum with cyclosporin. PMID- 1911329 TI - Generalized essential telangiectasia. PMID- 1911330 TI - Carbon dioxide laser treatment of multiple tricho-epitheliomas. PMID- 1911331 TI - Merkel cell tumour. PMID- 1911332 TI - White cells, skin blood flow and venous ulcers. PMID- 1911333 TI - Erythema nodosum and coeliac disease. PMID- 1911334 TI - Induction of ornithine decarboxylase in psoriatic skin. PMID- 1911335 TI - Pseudocyst of the auricle. A birthday ear pull. PMID- 1911336 TI - Effect of corticosteroid therapy in the leucocyte adherence deficiency syndrome. PMID- 1911337 TI - Topical treatment with the vitamin D3 analogue MC903 improves pityriasis rubra pilaris: clinical and immunohistochemical observations. PMID- 1911338 TI - Autocrine and/or paracrine mechanism operate during the growth of human bone marrow fibroblasts. AB - The growth of human marrow fibroblasts was studied at various plating cell densities. The growth rate of fibroblasts cultured with human plasma derived serum (PDS) increased depending on the cell density plated, whereas fibroblasts cultured with human serum proliferated almost independent of the cell density. Conditioned medium obtained from the culture with PDS at high cell density enhanced the growth of fibroblasts plated at low density, as well as that of fibroblast colony forming cells. Characterization of this conditioned medium showed heat unstable and acid stable peptide factor(s) with high molecular weight (approximately 10(6)) may be responsible for this activity. These results suggest that autocrine and/or paracrine mechanism can operate during the proliferation of marrow fibroblasts, a process thought to be involved in the progression of marrow fibrosis. PMID- 1911339 TI - Megakaryocyte potentiating activity of IL-1, IL-6 and GM-CSF as evaluated by their action on in vitro human megakaryocytic colonies. AB - We examined whether recombinant cytokines enhance the in vitro platelet production of interleukin-3 (IL-3)-induced human megakaryocytic colonies (Meg colony). We classified Meg-colonies into four categories based on platelet production during in situ observation on day 14: type 0, absence of cytoplasmic processes in a colony; type 1, one to three processes in at least one megakaryocyte in a colony; type 2, four to eight processes; type 3, more than nine processes or division of cytoplasm. Type 3 colonies were considered to be platelet-producing. In control cultures, type 1 Meg-colonies were dominant, followed by type 2, type 3 and type 0. Of the cytokines added at the initiation of culture, interleukin-1 alpha (IL-1 alpha), interleukin-6 (IL-6), and granulocyte/macrophage colony stimulating factor (GM-CSF) significantly increased the number of colonies. Furthermore, these three cytokines significantly elevated the proportion of type 3 colonies. Interleukin-4 (IL-4), granulocyte-CSF, macrophage-CSF and erythropoietin did not affect the colony count or distribution of colony type. IL-1 alpha, IL-6 and GM-CSF also significantly elevated the proportion of type 3 colonies, even when added to the culture on days 8 or 11. These results indicate that IL-1 alpha, IL-6 and GM-CSF promote platelet production of in vitro Meg-colonies. PMID- 1911340 TI - Effect of subcutaneously administered human recombinant erythropoietin on erythropoiesis in patients with myelodysplasia. AB - In a phase II study, 12 patients with a myelodysplastic syndrome (MDS) and anaemia (nine transfusion-dependent) were treated with recombinant human erythropoietin (rHuEpo) to assess the therapeutic effect on erythropoiesis and on transfusion requirement. Patients with a low risk of developing acute leukaemia were included, i.e. refractory anaemia (RA), RA with ringed sideroblasts (RARS) and RA with excess blasts (RAEB), providing the percentage of myeloblasts in the bone marrow did not exceed 10%. Recombinant HuEpo treatment was initiated at a dose of 50 units/kg body weight and administered subcutaneously three times weekly. At 3-week intervals the dose was increased with 50 units/kg per injection, until after 15 weeks a maximum dose of 250 units/kg three times weekly was reached. All patients completed the study. Recombinant HuEpo was well tolerated and no serious side effects were seen. There was no evidence of the emergence of a new malignant clone in response to rHuEpo as shown by sequential karyotyping. In none of the patients was an increase in haemoglobin level or a diminished red blood cell transfusion requirement seen. In four out of 10 evaluable sequential bone marrow smears, an increase in erythropoiesis was seen, suggesting stimulation of ineffective red cell production. One of these patients also showed a rise in reticulocyte count. The number of erythroid progenitor cells (BFU-E and CFU-E) in blood and bone marrow was not affected by rHuEpo treatment. Also no change in the number of myeloid progenitor cells (CFU-GM) in blood and bone marrow was noted. In conclusion, subcutaneous treatment with rHuEpo at dosages up to 250 units/kg body weight (three times weekly) fails to increase the haemoglobin level or to diminish the transfusion requirement in patients with MDS and anaemia. It is unclear whether higher doses of rHuEpo are effective or whether patients with less severe anaemia who are transfusion independent, have a higher likelihood of response. PMID- 1911342 TI - Inactivation of the retinoblastoma susceptibility gene in a human high grade non Hodgkin's lymphoma cell line. AB - We studied the expression of the retinoblastoma (RB) gene product (p105) in a B cell line established from a patient with non-Hodgkin's lymphoma (large cell type). The karyotype of this cell line, named Ri-1, showed amongst other changes an apparent deletion of one chromosome 13 on band q14. No p105 could be detected by immunoprecipitation analysis and Western blotting in Ri-1 cells. Northern blotting revealed that RB mRNA is not expressed in Ri-1. Southern blotting confirmed the loss of one RB allele but showed a normal gross structure of the remaining allele. This suggests that the inactivation of the RB gene in Ri-1 cells is due to deletion of one allele and point mutations or small deletions in the other, as is often the case in retinoblastomas. Our findings imply that inactivation of the RB gene may play a role in the pathogenesis of high grade malignant lymphomas and that studies of RB in primary lymphoma samples would be of interest. PMID- 1911341 TI - Rearrangements of the RAR-alpha gene in acute promyelocytic leukaemia: correlations with morphology and immunophenotype. AB - We have used genomic probes which specifically recognize DNA rearrangements of the RAR-alpha locus on chromosome 17q21 in patients with acute promyelocytic leukaemia (APL) and acute myeloid leukaemia (AML) subtypes. Molecular data were examined in comparison with morphological and immunophenotypic characterization at diagnosis in 20 hypergranular FAB M3 cases, five microgranular APL (M3v), 51 non-M3 AML and 12 myeloid CML blast crises. Rearrangements of the RAR-alpha locus were only detected in 23/25 APL cases and in none of the other FAB subtypes analysed. Surface marker characterization showed a consistent immunophenotypic profile--HLADR negative, CD9 and CD13/33 positive--in all M3 and M3v cases. Neither HLADR negativity nor CD9 positivity were associated with RAR-alpha rearrangements in non M3 AML. Our data indicate that RAR-alpha gene rearrangements are relevant diagnostic features of both M3 and M3v, and may prove useful molecular marker for follow-up analysis in APL patients. PMID- 1911343 TI - The in vivo kinetics of 111In- and 51Cr-labelled platelets: a comparative study using both stored and fresh platelets. AB - The in vivo kinetics of simultaneously injected 51Cr- and 111In-labelled platelets was investigated in 20 healthy male volunteers. The studies were carried out using both fresh platelets and platelets stored for 5 d at 22 degrees C; the disappearance of platelet-bound radioactivity was measured on whole blood samples as well as platelet pellets. Compared to 111In, the labelling efficiency was notably lower for 51Cr, and a higher amount of 51Cr was bound to contaminating red cells. As regards the fresh platelets, only small dissimilarities were observed in the in vivo kinetics obtained with the two labels. 51Cr yielded a slightly higher platelet recovery and longer T1/2 than 111In, when whole blood samples were used for calculations; no differences were seen when using platelet pellets. When stored platelets were studied, 51Cr gave significantly longer T1/2 and mean life-span (MLS) than did 111In. This difference was present for all mathematical models used for the calculation of MLS, and when whole blood samples as well as platelet pellets were employed. It was demonstrated that the estimation of MLS was also highly dependent upon techniques of blood sampling and curve fitting. Calculation, in which the initial data points were excluded, gave consistently longer MLS (P less than 0.0001), as compared to when all data points were included. Furthermore, when all survival studies were grouped together, calculations using platelet pellets gave a significantly (P less than 0.001) shorter platelet MLS than calculations using whole blood samples. It is concluded that both 51Cr and 111In are acceptable as radiolabels for both fresh and stored platelets. However, it appears that the viability of stored platelets may be influenced by the choice of label, and caution must be taken when these isotopes are used together in dual tracer experiments. Also, our results show that a meticulously standardized processing of blood samples and experimental data is required to enable interlaboratory comparisons of the results. PMID- 1911344 TI - A newly-characterized alpha-thalassaemia-1 deletion removes the entire alpha-like globin gene cluster in an Italian family. AB - We describe a new deletional form of alpha thalassaemia which encompasses the entire alpha-like globin gene cluster in a 15-year-old boy of Southern Italian descent. The deletion removes approximately 31 kb, the 5'-end point is located approximately 4 kb upstream of the xi gene, while the 3'-end point maps between the alpha 1- and theta 1-globin genes. The interaction of this deletion with the common-alpha 3.7 form gives origin to a classical form of haemoglobin (Hb) H disease in the propositus of this study. Deletional forms of xi alpha thalassaemia are uncommon in the Mediterranean basin; as for other unusual xi alpha-thalassaemia forms, heterozygotes for this mutation may escape detection in population surveys based on zeta and alpha probes. PMID- 1911345 TI - Red cell ABO incompatibility and production of tumour necrosis factor-alpha. AB - Tumour necrosis factor-alpha (TNF) is a major mediator of diverse pathophysiological events similar to those of haemolytic transfusion reactions (HTR), such as fever, intravascular coagulation and organ failure. However, the possible role of TNF in HTR has not been investigated. We have constructed an in vitro whole blood model of HTR to examine whether TNF may be produced in red cell ABO incompatibility. TNF was observed in plasma, in a dose dependent manner, when ABO incompatible red cells were added, but not with compatible (group O) cells. Plasma TNF levels were maximal at 2 h, and declined to control levels by 24 h. Haemolysis of incompatible red cells was accompanied by TNF production. Immune haemolysis induced TNF gene expression by buffy coat leucocytes, as determined by Northern blot analysis. Heat inactivation of plasma abolished TNF production, whereas prior treatment with interferon-gamma augmented the response. These results demonstrate that a major cytokine is produced in response to red cell incompatibility, and suggest that TNF may play a role in the pathogenesis of haemolytic transfusion reactions. PMID- 1911346 TI - Erythroid 5-aminolaevulinate synthase activity during normal and iron deficient erythropoiesis. AB - Reduced erythroblast 5-aminolaevulinate (ALA) synthase activity was observed during iron/haem deficient erythropoiesis. Enzyme activity was reduced approximately threefold to levels similar to those previously detected during sideroblastic erythropoiesis. This response would appear to be erythroblast specific as haem deficiency is known to stimulate hepatic ALA synthase activity. It is, however, unclear as to whether this reduced enzyme activity relates to iron deficiency or to the consequent haem deficiency. PMID- 1911347 TI - Iron absorption by hypotransferrinaemic mice. AB - Iron absorption rates by homozygous and wild-type mice from a hypotransferrinaemic mouse colony were examined with in vivo tied-off duodenal segments and in vitro incubated duodenal fragments. Enhanced initial rates of mucosal uptake and carcass transfer by homozygotes, compared to wild-types, were observed. The changes in vivo and in in vitro uptake kinetics resemble changes seen in iron deficient or hypoxic mice, suggesting that the liver iron loading shown by homozygotes is due to a failure of the normal mechanism for regulation of iron absorption. In vivo mucosal uptake and carcass transfer of radioiron showed an inverse correlation with liver non-haem iron content in homozygous hypotransferrinaemic mice, suggesting that some degree of control of absorption, albeit at markedly reduced sensitivity, can operate in these mice. No correlation between haemoglobin level and iron absorption was observed in homozygous hypotransferrinaemic mice, suggesting that this regulator of iron absorption does not function in these mice. The precise pathogenic mechanism of the enhanced iron absorption in hypotransferrinaemia remains to be determined. Mucosal transferrin levels were found to parallel serum transferrin levels in homozygotes, heterozygotes and wild-type mice. This supports previous suggestions that mucosal transferrin is derived from plasma transferrin and that the enhancement of iron absorption, by physiological mechanisms, does not require the presence of mucosal transferrin. PMID- 1911349 TI - Restitution of normal marrow morphology and karyotype in acute refractory acute promyelocytic leukaemia with all-trans retinoic acid. PMID- 1911348 TI - Pregnancy in congenital afibrinogenaemia: report of a successful case and review of the literature. PMID- 1911350 TI - Myelofibrosis in visceral leishmaniasis. PMID- 1911351 TI - Translocation (11;14)(q13;q32) without rearrangement of BCL1 oncogene in a case of chronic myeloproliferative syndrome. PMID- 1911352 TI - Trisomy 4 associated with acute lymphocytic leukaemia. PMID- 1911353 TI - Ultrastructural study of erythrocytes containing Pappenheimer bodies in a case of congenital sideroblastic anaemia (CSA). PMID- 1911354 TI - Spontaneous remission of chronic myeloid leukaemia with loss of the Philadelphia chromosome. PMID- 1911355 TI - A spontaneous deletion of beta 33/34 Val in exon 2 of the beta globin gene (Hb Korea) produces the phenotype of dominant beta thalassaemia. PMID- 1911356 TI - Folinic acid did not expand the peripheral blood stem cell pool during recovery from consolidation chemotherapy. PMID- 1911357 TI - Anti-neutrophil cytoplasm antibodies (ANCA) in a patient with the vasculitis of myelodysplasia. PMID- 1911358 TI - Natural-killer cell activity and cytogenetic response in chronic myelogenous leukemia treated with alpha-interferon. PMID- 1911359 TI - Reduced platelet PDGF levels in idiopathic myelofibrosis. PMID- 1911360 TI - Monocyte monolayer assay, autoanalyser values, and haemolytic disease of the newborn. PMID- 1911361 TI - Nitrendipine treatment and blood rheology in patients with sickle cell disease. PMID- 1911362 TI - Mega-dose methylprednisolone for aplastic anaemia. PMID- 1911363 TI - The treatment of myelofibrosis with alfa-interferon. PMID- 1911364 TI - Absence of graft-versus-leukemia (GVL) effect by leucocytes transfused: a prospective randomized trial in acute myeloid leukemia (AML) patients. PMID- 1911365 TI - mRNA-protein interactions regulate critical pathways in cellular iron metabolism. PMID- 1911366 TI - Role of spleen in hereditary spherocytosis: evidence for increased in vitro proteolysis of red cell membrane. AB - In vitro proteolysis of red cell membranes has been studied by means of electrophoretic separation on SDS-polyacrylamide gel of solubilized ghost proteins and subsequent densitometry of separated, stained bands; the amounts of major membrane proteins were measured in ghosts either with inhibited or with allowed proteolysis in the following cases: 15 patients suffering from hereditary spherocytosis (HS) with variable degree of spleen enlargement, eight cirrhotic patients with spleen enlargement and 12 healthy blood donors as control group. Proteolysis was present to a greater extent in HS patients with larger splenomegaly, lesser in HS with smaller splenomegaly, and was comparable to healthy controls both in splenectomized HS and in patients with spleen enlargement due to liver cirrhosis. The results suggest the involvement of splenomegaly in the enhancement of in vitro proteolysis in HS red cell membrane; it is probably attributable to joint effects of the damage induced in red cells by prolonged retention within haemolysing spleen together with the abnormalities genetically affecting the structure of HS red cell membrane. PMID- 1911367 TI - A simple and rapid method of direct sequencing using Dynabeads. PMID- 1911368 TI - Acquired beta thalassaemia trait in MDS. PMID- 1911369 TI - Homozygous non-deletion alpha 2 globin gene mutation (initiation codon mutation): clinical and haematological phenotype. PMID- 1911370 TI - Blindness as a complication of chronic granulocytic leukaemia. PMID- 1911371 TI - Documentation of allogeneic marrow engraftment by DNA analysis of urinary leucocytes. PMID- 1911372 TI - Steroid-resistant acquired pure red cell aplasia: a partial remission induced by recombinant human erythropoietin. PMID- 1911374 TI - Fatal haemophagocytic syndromes in HIV-antibody positive patient. PMID- 1911373 TI - Deletion of one GM-CSF allele and rearrangement of the other in a patient with myelodysplastic syndrome: possible loss of functions of a tumour suppressor gene closely linked to the GM-CSF locus on chromosome 5. PMID- 1911375 TI - A spontaneous mutation causing unstable Hb Hammersmith: detection of the beta 42 TTT----TCT change by CCM and direct sequencing. PMID- 1911376 TI - A pediatric case of pure red cell aplasia: successful treatment with anti lymphocyte globulin and correlation with in vitro T cell-mediated inhibition of erythropoiesis. PMID- 1911377 TI - Two cases of t(4;11) acute lymphoblastic leukemia (ALL) following ALL without the t(4;11): second or secondary leukemias? PMID- 1911378 TI - Cytokine levels in aggressive natural killer cell leukemia and malignant histiocytosis. PMID- 1911379 TI - Detection of minimal residual myeloma after bone marrow transplantation. PMID- 1911380 TI - Multinucleated giant myeloma cells. PMID- 1911381 TI - Red cell shape in different anticoagulants. PMID- 1911382 TI - Cyclosporin A treatment of pure red cell aplasia associated with B-CLL. PMID- 1911383 TI - Relationship between serum beta 2-microglobulin levels and total body tumour mass at diagnosis in myeloma. PMID- 1911384 TI - Autotransplants in acute leukaemia. PMID- 1911385 TI - The role of recombinant haematopoietic growth factors in human long-term bone marrow culture in serum-free medium. AB - We have previously reported prolonged in vitro maintenance of human bone marrow progenitor cells using a serum-free (SF) liquid culture system. The present study was undertaken to determine recombinant growth factor (rGF) requirement of long term marrow culture (LTMC) in absence of exogenous serum, to avoid interference of any undefined components. Our data clearly show that the presence of serum is a major obstacle to the correct evaluation of rGF activity. However, in SF conditions the sequential analysis of these rGFs, alone or in combination, clearly showed a stimulating activity of interleukin 3 (IL3), granulocyte macrophage colony-stimulating factor (GM-CSF) and erythropoietin (EPO) on granulopoiesis and erythropoiesis. Indeed, the cumulative number of progenitors recovered during an 8-week period exceeded the initial input by a factor of 1.7 for granulocyte-macrophage (CFU-GM), of 3 for erythroid blast-forming units (BFU E) and of 5.45 for CFU-E when EPO, GM-CSF and IL3 were combined. This study has confirmed that the system is able to sustain haematopoiesis for 8 weeks in a way similar to that in serum-dependent LTMC, despite diminished stromal adherent layer development which never covered more than 50% of the flask surface. We conclude that this defined SF-LTMC system provides a reproducible technique for studying human haematopoiesis. PMID- 1911386 TI - Biological significance of cell cycle kinetics in 128 standard risk newly diagnosed patients with acute myelocytic leukemia. AB - Bromodeoxyuridine (BrdU) was administered to 128 newly diagnosed patients with standard risk acute myelocytic leukaemia (AML) for cell cycle measurements. Labelling indices (LI) were obtained from both the bone marrow aspirate (BMasp) and biopsies (bx) and durations of S-phase (Ts) and total cell cycle time (Tc) were measured by double-labelling the S-phase cells in vitro with tritiated thymidine. Median LI BMasp was 8% and from BMbx was 25%. The median Ts was 12 h (range 3.1-35 h) and Tc was 48 h (range 11.5-211 h). All patients received induction therapy with a combination of cytosine arabinoside and an anthracycline. Outcome of therapy or FAB type were not related to cell cycle characteristics. Patients with above median LI BMasp, however, had longer remission durations (P = 0.03) as did patients with above median Ts (P = 0.03) and Tc (P = 0.03). Upon longer follow-ups, even some of the patients with slowly cycling myeloblasts have relapsed (log rank P = 0.453 and 0.203 for Ts and Tc respectively). We conclude that patients with rapidly cycling cells tend to relapse faster; however, slowly cycling nature of myeloblasts is not associated with curability. PMID- 1911387 TI - Co-expression of myeloid antigens in childhood acute lymphoblastic leukaemia: relationship with the stage of differentiation and clinical significance. AB - Co-expression of myeloid antigens on the leukaemic blast cells was evaluated in 532 children with a diagnosis of acute lymphoblastic leukaemia (ALL). Using a panel of monoclonal antibodies belonging to CD11b, CD13, CD14, CD15 and CD33 an overall incidence of 4.3% was found, with values ranging between 1.8% for CD14 and 6.1% for CD15. When the data were further dissected, a significantly higher incidence of co-expression was noted in null-ALL (15/70 cases = 21.4%), compared to cases expressing a more mature immunophenotype, i.e. common-ALL (7/394 cases = 1.7%) and T-ALL (1/68 cases = 1.4%) (P less than 0.001). In null-ALL, 9/15 patients were infants, five of whom with the t(4;11); two further children also had a t(4;11). The clinical outcome of the 23 cases which co-expressed myeloid antigens was unfavourable. Only two of the 15 null-ALL, two of the seven common ALL and the unique case with T-ALL are in fact in persistent first remission between 19 and 93 months from diagnosis. Though the overall incidence of childhood ALL expressing myeloid antigens is low, the evidence that this co expression may be related to an unfavourable clinical course and that it more frequently occurs in null-ALL, particularly in the first year of life, suggests that the routine assessment of myeloid antigens may allow to identify a subgroup of childhood ALL with a poor clinical outcome. PMID- 1911388 TI - Analysis of multidrug resistance (MDR-1) gene expression in chronic lymphocytic leukaemia (CLL). AB - Multidrug resistance (MDR) in cultured human cells is caused by the overexpression of the MDR-1 gene. This gene codes for P-glycoprotein, a proposed ATP-dependent drug efflux pump, which reduces the net intracellular accumulation of a large group of chemotherapeutic agents in resistant cells. We have measured the level of expression of the human MDR-1 gene in a series of patients with chronic lymphocytic leukaemia (CLL). Forty-eight patients included in the study were at different stages of disease and were either untreated or had been treated with alkylating agents or alkylating agents in combination with drugs of the MDR spectrum, and were tested over a period of 3 years. The level of MDR-1 expression was monitored by Northern blotting analysis using a specific cDNA hybridization probe and also after polymerase chain reaction (PCR) amplification of MDR-1 complementary DNA (cDNA). Four of 28 previously untreated patients showed intrinsically high levels of MDR-1 mRNA while 5/19 treated patients had elevated MDR-1 expression. Elevated MDR-1 expression in treated patients was unrelated to the type of chemotherapy and was independent of previous exposure to drugs of the MDR spectrum. Intrinsic MDR-1 gene expression in positive patients did not appear to influence their response to chemotherapy with non-MDR drugs such as alkylating agents. PMID- 1911389 TI - Antithrombin Glasgow II: alanine 382 to threonine mutation in the serpin P12 position, resulting in a substrate reaction with thrombin. AB - A female with recurrent thrombosis was found to have a functional abnormality of antithrombin, with a ratio of functional to immunological activity in plasma of approximately 50%. Crossed immunoelectrophoresis in the presence of heparin was normal, indicating an abnormality of the reactive site, rather than the heparin binding domain. Accordingly, the antithrombin was isolated by heparin-Sepharose chromatography: this produced a mixture of normal and variant antithrombin, as the patient was heterozygous for the abnormality. To remove the normal component, the antithrombin was passed through a column of thrombin-Sepharose. On sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE), prior to its application to thrombin-Sepharose, the antithrombin migrated as a single band with identical mobility to that of normal antithrombin. After thrombin-Sepharose, the purified variant component was proteolysed, and migrated as two components, one with a reduced and one with enhanced mobility under non-reducing conditions. This demonstrated that the variant was unable to form stable inhibitor-thrombin complexes and was cleaved in a substrate reaction with thrombin. One site of cleavage was unambiguously ascertained to be the Arg 393-Ser 394 reactive site bond, by NH2 terminal sequencing of the cleaved variant antithrombin: 10 steps beginning at the P1' position, Ser-Leu-Asn-Pro-Asn-Arg,..., were clearly identified. The mutation responsible for this defect was studied by polymerase chain reaction (PCR) amplification of exon 6 of the antithrombin gene and direct sequencing of the amplified product. The presence of both a G and A in the first position of codon 382, identified the mutation GCA to ACA, which results in the substitution of Ala 382 to Thr. This is identical to that reported for antithrombin Hamilton (Devraj-Kizuk et al, 1988), although antithrombin gene polymorphism analysis suggests that the antithrombin Glasgow II mutation has arisen independently. We have recently shown (Caso et al, 1991) that mutation at a nearby position, Ala 384 to Pro, also transforms another variant, antithrombin Vicenza/Charleville, into a substrate for thrombin. The present results with antithrombin Glasgow II suggest that all the alanine residues at the base of the reactive site loop in positions P12-10 may be important for the formation of a stabilized inhibitor-thrombin complex. PMID- 1911390 TI - Primary thrombocythaemia associated with systemic mastocytosis: a report of five cases. AB - Mastocytosis is an uncommon disease characterized by a proliferation of tissue mast cells involving various organs, particularly the bone marrow. Though rare, the association of mastocytosis and haematological malignancies is well established. However, the frequency of mastocytosis reported in patients with essential thrombocythaemia is relatively low. We report five cases of such an association. Our five patients were undergoing evaluation for thrombocyte when the bone marrow biopsy revealed the presence of mastocytosis. The pathogenetic significance of this association is poorly understood. The different hypotheses are discussed. PMID- 1911391 TI - A new beta-thalassaemia frameshift mutation detected by PCR after selective hybridization to immobilized oligonucleotides. AB - A previously undescribed mutation (-1, +3, codon 24) causing beta-thalassaemia was identified in an Egyptian patient. It consists in the concomitant deletion of a G in codon 24 and its replacement with the new trinucleotide CAC, thus resulting in the shift of the beta-globin reading frame. The sequence of the chromosome of interest was isolated from the homologous one by means of selective hybridization to an immobilized oligonucleotide. The presence of this mutation in the proband's family was confirmed by dot blot hybridization with an oligonucleotide probe. PMID- 1911392 TI - Establishment of imaginal discs and histoblast nests in Drosophila. AB - In Drosophila the homeotic genes of the bithorax-complex (BX-C) and Antennapedia complex (ANT-C) specify the identity of segments. Adult segment primordia are established in the embryo as the histoblast nests of the abdomen and the imaginal discs of the head, thorax and terminalia. We have used a molecular probe for the limb primordia and in vivo culture to describe the nature of the adult primordia in mutants in which the pattern of homeotic gene expression was altered. The results suggest that the histoblast or disc 'mode' of development is initiated by the extended germ band stage through activity of the BX-C and ANT-C and is relatively inflexible thereafter [corrected]. PMID- 1911393 TI - Segmentally restricted, cephalic expression of a leucine zipper gene during Drosophila embryogenesis. AB - The expression pattern and DNA sequence of a newly identified gene, CNC (cap'n'collar), suggest a role for this gene in cephalic patterning during Drosophila embryogenesis. In situ hybridization reveals transcripts localized to the mandibular segment and the hypopharyngeal and labral primordia first detectable in late blastoderm stages. Sequence analysis of cDNA clones from the CNC locus shows the CNC gene product to be related to transcription factors of the leucine zipper (bZIP) class. Based on its protein sequence, we propose that CNC is a subunit of a heterodimeric regulatory protein involved in the control of head morphogenesis. PMID- 1911394 TI - Cell-specific, developmentally and hormonally regulated expression of the rabbit uteroglobin transgene and the endogenous mouse uteroglobin gene in transgenic mice. AB - We have generated a transgenic mouse line by introducing the rabbit uteroglobin gene with 4 kb of 5'-flanking DNA and 1 kb of 3'-flanking DNA into the mouse germ line via microinjection into fertilized oocytes. Expression of the rabbit uteroglobin transgene was examined and compared with the endogenous mouse uteroglobin gene. Both genes are expressed in the lung, male genital tract and uterus. In the lung, mRNA expression is enhanced by glucocorticoids and restricted to the Clara cells that line terminal and respiratory bronchioli. During embryonic lung development, transcripts are first detected at day 17. Expression in the uterus is restricted to the glandular epithelium and can be induced by sequential treatment with estrogens and progesterone. In the uterus of these pseudopregnant mice the level of rabbit uteroglobin transcripts is higher than that of the mouse endogenous uteroglobin transcripts. In the male genital tract, expression of both genes is restricted to the epithelial layers of the vesicular gland, vas deferens and epididymis. Our results indicate that the rabbit uteroglobin gene together with 4 kb of 5'-flanking DNA and 1 kb of 3' flanking DNA contains the information required for cell type-specific, developmentally, and hormonally regulated expression. PMID- 1911396 TI - The vegetalizing factor from chicken embryos: its EDF (activin A)-like activity. AB - The erythroid differentiation capacity of the HPLC-purified mesoderm- and endoderm-inducing vegetalizing factor from chicken embryos and of recombinant erythroid differentiation factor (EDF = activin A), an evolutionary highly conserved member of the TGF-beta protein superfamily have been compared. Both factors stimulate the synthesis of hemoglobin in erythroleukemia cells in the same concentration range. The EDF-activity of the mesoderm-inducing HPLC fractions is inhibited by follistatin, an EDF-binding protein. The factor induces in ectoderm of Triturus taeniatus all kinds of mesodermal organs. The wide spectrum of organs is very likely to be induced by secondary interactions. At higher concentration (15 ng/ml), notochord- and endoderm-like tissues are induced in a high percentage. PMID- 1911395 TI - Intracellular sperm/egg interactions in Drosophila: a three-dimensional structural analysis of a paternal product in the developing egg. AB - During fertilization in Drosophila, a single 1.75 mm long sperm enters the egg through the anterior end. Using a sperm-specific monoclonal antibody and indirect immunofluorescence of whole fixed eggs and embryos, intracellular interactions between the sperm and egg are examined as they occur inside the fertilized egg. The sperm nucleus remains attached to the axoneme throughout the entire process of fertilization including the stages of pronuclear maturation, pronuclear fusion and karyogamy indicating an intracellular function for the sperm during these stages. Optical sections and three-dimensional reconstructions of whole mount specimens reveal that a stereotypically folded structure forms during fertilization strongly suggesting that this structure positions the male pronucleus in the proper region of the egg in anticipation of pronuclear fusion. This, and the appearance of regional structural changes in the sperm upon entry suggests that sperm are localized via specific interactions with the maternal cytoplasm. Following fertilization and during the ensuing cleavage divisions, the sperm remains intact and localized at the anterior end of the egg. During cellular blastoderm formation the sperm tail is sequestered into the anterior yolk area where it continues to persist well into embryonic development. This structural analysis identifies intracellular sperm/egg interactions as an important aspect of fertilization, and provides a unique model system for the study of sperm/egg interactions not presently available in other systems. PMID- 1911397 TI - Cellular interactions involved in the determination of the early C. elegans embryo. AB - Classical work implied that early nematode embryogenesis is completely mosaic. This view was lately challenged by the demonstration that in C. elegans an early interaction has to occur to induce the production of muscle from a blastomere. Here, early embryonic blastomeres were inactivated by laser microsurgery. The cell lineages of irradiated embryos were compared to those of intact embryos. It is shown that one blastomere, MS, is required for the specification of mesodermal pharyngeal fates and another blastomere, P2, for the specification of hypodermal fates from the descendants of the AB blastomere, whereas the proper specification of the nervous system requires the presence of both. The irradiation of a third blastomere shows that interactions also occur within the ectoderm. I propose that the body plan of the C. elegans embryo may be established by two primary signals followed by secondary interactions. The suggested mechanisms are reminiscent of those involved in amphibian development. PMID- 1911398 TI - A preliminary report of a surveillance scheme of occupational asthma in the West Midlands. AB - The results from the first year of a notification scheme for occupational asthma in the West Midlands Region are presented. The scheme includes recognised new and old cases of occupational asthma. Thirty new cases were recognised per million general working population in the first year. Cases recognised in different occupational groups ranged from 154 per million painters and assembly workers to three per million clerical staff. Analysis of the agents to which workers with recognised occupational asthma were exposed identified commonly recognised agents such as isocyanates, colophony, and flour and generally less well recognised ones such as oil mists. The distribution of new and old reported cases, including those receiving compensation from the Department of Social Security, were calculated by health authority using estimated working population as the denominator. The number of reported cases varied from 303 per million in a semi urban health authority that has a respiratory physician with a special interest in occupational asthma to less than 30 cases per million in eight health authorities. The most likely cause for these differences is lack of ascertainment. PMID- 1911399 TI - Occupational exposure and cancer of the pancreas: a review. AB - Many hypotheses have been proposed about the aetiology of cancer of the pancreas, especially concerning the effects of tobacco, coffee, alcohol, diet, and pancreatic pathology. Results of numerous epidemiological studies are, however, inconsistent. Chemical carcinogens have been implicated as possible risk factors. Animal studies have been carried out to determine the role of these chemical factors but, except for nitrosamines and their derivatives (components of tobacco), chemicals have not been proved carcinogenic for the pancreas. Many studies have also been conducted among occupational groups. Several of them showed an excess risk of cancer of the pancreas, especially in the chemical and petroleum industries. The lack of accuracy about the nature of products used, however, does not permit a definitive conclusion as to their carcinogenic role. This paper is a review of publications about occupational exposures and cancer of the pancreas. PMID- 1911400 TI - Respiratory symptoms in children at schools near a foundry. AB - A survey was carried out in response to complaints of increased respiratory symptoms in children at schools near a foundry in Walsall, West Midlands. Air monitoring around the factory had shown concentrations of formaldehyde most of which were orders of magnitude below the current occupational exposure limit of 2.5 mg/m3, although concentrations up to 0.3 mg/m3 had been recorded over short periods. The study sample comprised children aged 6.8-7.8 years from 39 schools in the borough. Information about respiratory symptoms and potential risk factors for respiratory disease was elicited from parents by a self administered questionnaire. Data were obtained on 1334 children, a response rate of 81.8%. The prevalences of reported wheeze (11.1%), breathlessness (7.7%), and chest discomfort (8.6%) were similar to those in an earlier survey carried out in Southampton by the same method at the same time of year. Cough (prevalence = 18.4%) and chestiness at night (14.6%) were significantly less common than in Southampton. When sex, social class, housing tenure, passive smoking, and parental history of asthma were taken into account, the prevalences of symptoms at schools within one mile of the foundry were generally lower than in other parts of Walsall. These findings give no support to the hypothesis that foundry emissions cause respiratory disease in children, although an adverse effect in a few sensitive children cannot be ruled out. PMID- 1911401 TI - Physical fitness and occupational demands of the Belfast ambulance service. AB - The objectives of this study were to evaluate the current fitness of an area ambulance service based in Belfast and to quantify the physiological demands of accident and emergency work. From a total staff of 230, 105 (46%) volunteered to undergo a series of fitness tests subject to health state. Results based on body mass indices showed that 52% of subjects could be classified as overweight and 10% of subjects as obese. Fitness levels were similar to other comparable samples and showed the expected but not inevitable decrease with age. A simple work related task (walking at 6 km/h) performed in the laboratory showed that 54% of men over 40 years of age and 24% under 40 found it taxing. This would favour selection for accident and emergency work on the basis of functional capacity rather than chronological age. Accident and emergency work consisted of long periods of inactivity interspersed with shorter periods of relatively intense activity, often above the anaerobic threshold. Lactate concentrations measured during a staged emergency incident also suggested that personnel may work at intensities exceeding their anaerobic threshold. The incorporation of physical fitness standards in the ambulance service may be appropriate and consideration should be given to a reduced age of retirement. PMID- 1911402 TI - Incidence of leukaemia and brain tumours in some "electrical occupations". AB - A 19 year follow up study was conducted to explore the association between occupations expected to be exposed to electromagnetic fields and the occurrence of leukaemia and brain tumours. Incidence of cancer between 1961-79 was calculated and the standardised morbidity ratio (SMR) with a 95% confidence interval (95% CI) was related to that of all Swedish working men. For all the selected "electrical occupations" the SMRs for total leukaemia and brain tumours were near unity. Increased risks were noted for all leukaemia among electrical/electronic engineers and technicians, (SMR 1.3; 95% CI 1.0-1.7) as well as in the sub-groups of telegraph/telephone (2.1; 1.1-3.6) and machine (2.6; 1.0-5.8) industries. Risk for chronic lymphoid leukaemia was increased in the same occupational category (1.7; 1.1-2.5) and in the sub-group of machine industry (4.8; 1.0-14.0), as well as for all linesmen (2.0; 1.0-3.5) and power linesmen (2.8; 1.1-5.7). Risk for acute myeloid leukaemia was increased among all miners (2.2; 1.0-4.1) and miners working in iron/ore mines (5.7; 2.1-12.4). Increased risk for all brain tumours (2.9; 1.2-5.9) and glioblastomas (3.4; 1.1 8.0) appeared among assemblers and repairmen in radio and TV industry. Raised risk for all brain tumours was seen for all welders (1.3; 1.0-1.7) and welders in iron/steel works (3.2; 1.0-7.4) and risk for glioblastomas was also increased for all welders (1.5; 1.1-2.1). No major changes in relative risk estimates were noted after the exclusion of persons who were over 65 at the time of diagnosis. Although a homogeneous pattern of increased risks of leukaemia or brain tumour was not noted, the hypothesis that magnetic fields might play a part in the origin of cancer cannot be rejected. PMID- 1911403 TI - Characterisation of respiratory health and exposures at a sintered permanent magnet manufacturer. AB - Sintered permanent magnets are made from the powdered metals of cobalt, nickel, aluminium, and various rare earths. During production, exposure to respirable crystalline silica and asbestos may also occur. Reported here is a cross sectional study of 310 current and 52 retired hourly employees who worked 10 or more years making sintered magnets. Each participant had a chest radiograph, spirometry, and completed a respiratory questionnaire. Illness logs were also reviewed to calculate the incidence of recorded respiratory disorders. The prevalences of abnormalities in pulmonary function and respiratory symptoms were not higher than found in an external referent population. Although the prevalence of diffuse parenchymal opacities consistent with pneumoconiosis (four workers) was similar to the referent population, one worker had radiographic findings consistent with silicosis and two workers had profusion scores of 1/2 or above, not seen in the referent group. The incidence of reported respiratory conditions in the log, including asthma, was 10 times that of other manufacturers in the same industrial classification category. Excessive exposures to cobalt, nickel, and respirable silica were shown by environmental measurements. PMID- 1911404 TI - Biological monitoring of occupational exposure to tetrahydrofuran. AB - Occupational exposure to tetrahydrofuran (THF) was studied by analysis of environmental air, blood, alveolar air, and urine from 58 workers in a video tape manufacturing plant. Head space gas chromatography (GC) with an FID detector was used for determination of THF concentration in alveolar air, urine, and blood. Environmental exposure to THF was measured by personal sampling with a carbon felt passive dosimeter. When the end of shift urinary THF concentrations were compared with environmental time weighted average (TWA) values, urinary THF concentration corrected for specific gravity correlated well with THF concentration in air (r = 0.88), and uncorrected urinary THF concentration gave a similar result (r = 0.86). Correction for creatinine in urine weakened the correlation (r = 0.56). For exposure at the TWA concentration of 200 ppm the extrapolated concentration of THF was 33 mumol/l in blood and 111.9 mumol/l (61 mumol/g creatinine) or 109 mumol/l at a specific gravity of 1.018 in urine. The correlation between exposure to THF and its concentration in exhaled breath and blood was low (r = 0.61 and 0.68 respectively). Laboratory methodological considerations together with the good correlation between urinary THF concentration and the environmental concentration suggest that THF concentration in urine is a useful biological indicator of occupational exposure to THF. PMID- 1911405 TI - Experimental evidence for the possible exposure of workers to hexachlorobenzene by skin contamination. AB - The absorption of dermally applied 14C-hexachlorobenzene (14C-HCB; ranging from 2.5 to 2.6 mg/4 cm2) was investigated in the rat. The absorbed portion increased from 1% at six hours to 9.7% at 72 hours after dosing and blood concentrations of 14C increased linearly with time. The rate of absorption was 3.51 (SD 0.81) micrograms/h/4 cm2 and the absorption constant 1.40 (SD 0.33) x 10(-3)/h. Washing with soap at six hours after dosing removed 34% of the dose and decreased absorption by 50% in the next 66 hours. Finally, the compartment model, which incorporated the absorption constant, simulated the time profile of HCB kinetics in blood, and that of cumulative excretion in rats. The model with the absorption constant for the rat was then scaled up for a 70 kg worker, whose exposure was assumed to be exclusively dermal. A rough dermal contamination, which corresponds to the tentative HCB critical blood concentration of 200 ppb, was calculated for different simulated biological half lives. It was 18.2 mg for 100, 5.02 mg for 365, and 2.56 mg for 730 day half lives. The study indicates that dermal contamination can be a source of HCB body burden, and that personal hygiene, such as taking a shower and hand washing is likely to have a profound influence on the body burden of HCB. PMID- 1911406 TI - Airway oedema and obstruction in guinea pigs exposed to inhaled endotoxin. AB - Protein extravasation and airway conductance (SGaw) were examined in awake guinea pigs exposed to inhaled endotoxin or saline for three hours. A significant increase in protein extravasation (as estimated by the leakage of protein bound Evans blue dye) was seen in the conducting airways of endotoxin exposed animals compared with saline exposed animals. Mean dye extravasation was significantly increased by one to threefold in the mainstem and hilar bronchi of endotoxin exposed animals. These changes in extravasation were accompanied by decrements in pulmonary function and by an influx of polymorphonuclear leucocytes into the airway wall. The SGaw decreased significantly by 60-90 minutes into exposure to endotoxin and had decreased by 22% and 34% at the end of exposure in the low and high dose endotoxin groups, respectively. Similar findings were obtained in animals exposed to cotton dust. Contrary to studies suggesting that platelet activating factor (PAF) is involved in the systemic and peripheral lung effects of endotoxin, pretreatment with the PAF antagonist WEB2086 did not prevent the conducting airway injury produced by inhaled endotoxin. PMID- 1911408 TI - Occupational asthma due to hexahydrophthalic anhydride: a case report. PMID- 1911407 TI - Ethanol and food deprivation induced enhancement of hepatotoxicity in rats given carbon tetrachloride at low concentration. AB - Effects of chronic ethanol consumption and one day food deprivation on the hepatotoxicity of low dose carbon tetrachloride (CCl4; 0 to 100 ppm inhalation for eight hours) in rats were investigated by using biochemical and histopathological methods. Liver malondialdehyde (MDA) contents were significantly increased by exposure to 5 ppm to 50 ppm CCl4 in ethanol treated rats or by exposure to 25 ppm to 50 ppm CCl4 in food deprived rats but not in rats without ethanol or food deprivation. The MDA concentrations reached a maximum at 10 ppm and 50 ppm CCl4 in ethanol treated and food deprived rats, respectively, and decreased to the non-exposed concentration at 100 ppm CCl4. At greater than or equal to 50 ppm CCl4 plasma MDA contents increased significantly only in ethanol treated rats. None of the exposure concentrations influenced plasma glutamic-oxaloacetic transamidase (GOT) and glutamic-pyruvic transaminase (GPT) activities in rats that were only exposed to CCl4 whereas exposure to 10 ppm or higher concentrations combined with ethanol increased both activities. To a lesser extent food deprivation combined with exposure to greater than or equal to 25 ppm CCl4 had the same effect. No histopathological changes were found in the liver of rats exposed to less than or equal to 10 ppm CCl4, and only a few ballooned hepatocytes were seen in centrilobular areas when exposure was 25 ppm or higher. The presence of ballooned and hepatocytes became a regular feature of mid-zonal areas in ethanol treated rats and in the centrilobular areas of food deprived rats after exposure to /=25 ppm and >/=50 ppm respectively. These results indicate that consumption of ethanol and food deprivation potentiate CCl(4) induced hepatic damage even at low concentrations of CCl(4) by promoting lipid peroxidation. Thus heavy drinking may be a risk factor for CCl(4) induced hepatic damage even though the CCl(4) concentration is as low as the threshold limit value. PMID- 1911409 TI - Biological effect monitoring of occupational exposure to 1,3-dichloropropene: effects on liver and renal function and on glutathione conjugation. PMID- 1911410 TI - Application of ELISA-ABC method to the identification of minute human bloodstains. AB - Bloodstained threads (1 cm in length) were tested to identify human origin by a direct ELISA-ABC method using biotinylated antibody against human HbA0. By this method human bloodstains were clearly distinguishable from bloodstains of other species including Japanese monkey. The minimum detection limit of bloodstains prepared from undiluted human whole blood was 1:5, 120 (28 ng Hb) and that of bloodstains from diluted human whole blood was 1:640-1:1, 280. Human Hb was more easily detectable in bloodstains prepared from diluted human blood after extraction with 5% ammonia than after extraction with phosphate-buffered saline. PMID- 1911411 TI - Postmortem changes in hapten-specific IgE antibody responses in mice. AB - This Study was carried out to examine the post-mortem stability of hapten specific immunoglobulin E (IgE) antibody in mice by the passive cutaneous anaphylaxis test in rats. In vitro IgE antibody responses in blood were stable for 3 days at room temperature. Even in cases when blood could not be obtained from the cadaver it was possible to measure the hapten-specific IgE antibody response up to 3 days after death using the supernatant of the visceral homogenates. PMID- 1911412 TI - Fatality due to inhalation of dimethyl sulfide in a confined space: a case report and animal experiments. AB - A man was found dead in a tank where gaseous dimethyl sulfide (DMS) was present. The concentrations of DMS in the blood and tissue samples were measured by gas chromatography. Mice were experimentally exposed to various concentrations (5% 55%) of gaseous DMS in a confined space and the course of death and DMS distribution in the bodies were observed to obtain diagnostic criteria for DMS poisoning. As a result it was considered that the cause of death of the victim was consistent with a combination of DMS poisoning and asphyxia due to a hypoxic atmosphere. PMID- 1911413 TI - Extraction strategy for obtaining DNA from bloodstains for PCR amplification and typing of the HLA-DQ alpha gene. AB - A simple, practical approach for the extraction of PCR-amplifiable DNA for the HLA-DQ alpha gene from bloodstains deposited on various substrates is described. DNA from bloodstains is purified using Chelex 100 ion-exchange resin and then amplified. If amplification is not achieved, the extract is washed through a Centricon 100 dialysis/concentration tube. If the second amplification of this extract produces a negative result, the extract is processed with Chelex 100 again. This approach has been found to be reliable, safe, efficient and economical. PMID- 1911414 TI - Production and characterization of a monoclonal antibody to ABH-carrying alpha 2 seminoglycoprotein for ABO grouping of semen by ELISA. AB - BALB/c mice were immunized with alpha 2-seminoglycoprotein (A2SGP), the lymph node cells were fused with P3U1 myeloma cells and cultured by the conventional technique. Four antibody-producing hybridoma clones were established and antibody containing ascitic fluid obtained. The antibody was directed to the protein backbone of A2SGP and not to ABH antigenic determinants and did not cross-react with saliva or vaginal secretions. When tested in an indirect ELISA the anti A2SGP antibody had a titer of 512000. The anti-A2SGP was used in a capture ELISA (or sandwich ELISA) in which wells were coated with this antibody to capture A2SGP in semen, and the captured A2SGP was detected with anti-A, anti-B or anti-H peroxidase conjugate and peroxidase-labeled second antibody. This ELISA allowed correct ABO grouping even of 1:12,800 or higher dilutions of semen. When the ELISA was applied to ABO grouping of seminal fluids mixed with vaginal secretions only the seminal ABH antigens could be detected. The results strongly suggest the potential usefulness of monoclonal anti-A2SGP in the investigation of rape cases. PMID- 1911415 TI - Detection of foreign particles in traumatized skin. AB - The aims of the medico-legal investigation of wounds are a description of the wound morphology, the characterization of the force used and finally identification of the weapon. The demonstration of foreign particles, such as wood particles, paint fragments, synthetic materials, sand or gravel particles, powder residues and rust particles, in the depth of a wound or in the surrounding area can be of great value. In the present series of experiments the suitability of imaging methods (low energy X-ray imaging, direct X-ray magnification, nuclear magnetic resonance) for the detection of relevant foreign particles has been investigated. PMID- 1911416 TI - Child neglect followed by marked thymic involution and fatal systemic pseudomonas infection. AB - The case of a 9-month-old baby girl who failed to develop normally due to nutritional neglect and secondary immunodeficiency characterized by marked thymic involution is reported. The child died of systemic Pseudomonas aeruginosa (P. aeruginosa) infection manifested in pneumonia, lung abscesses, bacterial endocarditis and ecthyma gangrenosum. At autopsy the child was 64 cm in height (normal for a 4- to 5-month-old child) and 5.1 kg in weight (normal for a 2- to 3 month-old child). Multiple gangrenous ecthymas, consisting of deep ulcers, induration and inflammation, were observed in the skin over the entire body. The lungs showed hemorrhagic pneumonia, multiple lung abscesses, and necrotizing arteritis in the abscesses and surrounding areas. The thymus weighed 2.3 g and showed marked involution. Histological examination showed so-called nutritional thymectomy characterized by severe cortical atrophy and clustering, cystic dilation and amorphous changes of the Hassall's corpuscles. In the heart, dark brown verrucae were present at the attachment sites of the tendinous cords of the papillary muscle in the anterior and posterior cusps of the mitral valve, suggesting infectious endocarditis. Bacteriological examination demonstrated P. aeruginosa in the ecthymas, lung abscesses and blood. As primary immunodeficiency was considered unlikely, immunodeficiency secondary to thymic involution following malnutrition seemed to have led to a fatal systemic infection with P. aeruginosa, whose virulence is generally weak. This suggests a close association of the development of such infection and immunodeficiency with child neglect. PMID- 1911417 TI - Unusual finding in a water-logged corpse--hyperchylomicronemia or pulmonary fat embolism? AB - During excavation work at the bank of the River Inn the corpse of a 32-year-old alcoholic male was recovered. Head injuries suggested a crime of violence. Postmortem examination demonstrated conspicuous milky turbidity of the blood, which was found by laboratory testing to be due to hyperchylomicronemia. The findings are interpreted and their relevance to the determination of postmortal head injuries is discussed. The inadequacy of double-edged knife specimens and frozen-section biopsies for the estimation of pulmonary fat embolism as a vital reaction is considered. PMID- 1911418 TI - Codeine concentrations in human samples in a case of fatal ingestion. AB - Capillary gas chromatography coupled to mass spectrometry was employed to quantify codeine in biological fluids and tissues in a death attributed to oral codeine ingestion. The blood concentration of codeine was 22.1 mg/l. Results are discussed in the light of the existing literature. PMID- 1911419 TI - High level expression of biologically active estrogen receptor in Saccharomyces cerevisiae. AB - Biochemical over-expression of the human estrogen receptor was achieved using a Saccharomyces cerevisiae expression system. The receptor was produced as a novel ubiquitin fusion protein. This fusion protein is short lived in the cell and is processed to produce unfused receptor shortly after folding. Conventional high copy expression plasmids produced receptor to about 0.04% of the total soluble protein. By incorporating a defective leu2 allele into these vectors, an additional 5-fold increase in receptor production was obtained. The recombinant receptor was undergraded, soluble and biologically active. Conventional methods of disrupting cells using glass beads had a detrimental effect on the ability of the receptor to bind hormone. Enzymatic digestion of the cell wall followed by hypotonic shock liberates the receptor that quantitatively binds estrogen. PMID- 1911420 TI - Electron microscopic demonstration of glucocorticoid recognition sites on isolated rat hepatocytes. AB - Ultrastructural evidence is presented for the presence of membrane-bound glucocorticoid recognition and binding sites. Corticosterone was derivatized at 3 different positions and coupled covalently to bovine serum albumin (BSA). All three derivatives competed for binding of [3H]corticosterone by isolated rat hepatocytes. The most effective competitor, corticosterone-succinate-BSA (CSB), was adsorbed onto colloidal gold particles (CSB-gold, 17 +/- 3 nm dia). When isolated rat hepatocytes or mouse pituitary tumor cells (AtT 20) are incubated with CSB-gold, specific binding in the microvilli-rich region of these cells is seen. This binding of CSB-gold is reduced by about 50% in the presence of unlabelled CSB or corticosterone. PMID- 1911421 TI - Contrasting effects of sn-1,2-dioctanoyl glycerol as compared to other protein kinase C activators in adrenal glomerulosa cells. AB - Angiotensin II acts on adrenal glomerulosa cells to induce the phospholipase C mediated generation of inositol trisphosphate and sn-1,2-diacylglycerol as the major products of inositol phospholipid breakdown. This last product is known to activate protein kinase C, but its role in the action of angiotensin II on steroidogenesis has not been defined. We report herein that, in bovine adrenal glomerulosa cells, protein kinase C activators, such as phorbol 12,13-dibutyrate, 12-O-tetradecanoylphorbol-13-acetate, mezerein and sn 1,2 oleoyl acetoylglycerol, each failed to increase steroidogenesis. These results contrast with our recent report on the enhancement of aldosterone output by sn-1,2-dioctanoylglycerol (DiC8) [J. Steroid Biochem. 35 (1990) 19-33]. In addition, the difference between DiC8 and the other protein kinase activators was also observed in the pattern of 86Rb efflux from preloaded glomerulosa cells; only DiC8 mimicked the effect of angiotensin II on ion fluxes. Furthermore, staurosporine, a potent inhibitor of protein kinase C, was capable of amplifying the aldosterone output induced by a maximally effective concentration of DiC8 or angiotensin II. These data suggest that the effect of the cell permeant DiC8 on aldosterone biosynthesis either is not mediated by protein kinase C activation, or is mediated by a phorbol ester insensitive isoenzyme of protein kinase C. PMID- 1911423 TI - Effect of estradiol and progesterone on phosphatidylinositol metabolism in the uterine epithelium of the mouse. AB - The effect of estradiol and progesterone on uterine phosphatidylinositol (PtdIns) metabolism was examined in whole uteri and separated uterine luminal epithelium of ovariectomized mice. Incorporation of [3H]myo-inositol in vitro, into inositol containing phospholipids extracted from whole uteri, increased in mice injected with estradiol, with maximal incorporation at 9-12 h. The breakdown of PtdIns to inositol polyphosphates was also stimulated in whole uteri by estrogen, with an abrupt increase between 6 and 9 h. Comparable increases in both processes occurred in the uterine epithelium after estrogen stimulation and were inhibited by progesterone pretreatment which by itself had little or no effect. These results suggest that PtdIns metabolism is involved in the stimulation of uterine epithelial cell proliferation by estrogens, and its inhibition by progesterone. PMID- 1911422 TI - Non-classical androgenic actions of RU38486 in androgen-responsive Shionogi carcinoma 115 cells in serum-free culture. AB - Antiglucocorticoid and antiprogestin RU38486 (RU486) stimulated the growth of highly androgen- and moderately glucocorticoid-sensitive SC-3 cells (a cloned cell line from Shionogi mouse mammary carcinoma 115) in a dose-dependent manner. A maximal 8-fold stimulation of growth by RU486 has been observed at 10(-7) M in a serum-free medium and its potency has been found to be almost the same as that of dexamethasone (Dex). The growth rate of SC-3 cells treated by triamcinolone acetonide (TA) or Dex combined with RU486 at 10(-9)-10(-7) M was enhanced compared to cells treated by TA or Dex alone, indicating that RU486 had additive rather than antagonistic effects. Our previous study revealed that RU486 could compete with the specific uptake of [3H]testosterone in intact SC-3 cells at relatively low affinity and the present study showed that the stimulatory effect of RU486 on the growth of SC-3 cells was significantly inhibited by pure antiandrogen flutamine and that half-maximal inhibition by flutamine was achieved at 10(-6) M. Moreover, we demonstrated that the conditioned medium from RU486 stimulated SC-3 cells contained growth-promoting activity which caused a 3.5-fold increase in DNA synthesis by SC-3 cells in the absence of RU486 and which was abolished by treatment with heparin-Sepharose. These results indicate that RU486 induced growth of SC-3 cells may be expressed as an androgenic activity through androgen receptor and mediated by a heparin-binding growth factor. PMID- 1911424 TI - Characterization of estrogen and antiestrogen binding to the cytosol and microsomes of breast tumors. AB - The binding of [3H]estradiol and [3H]hydroxytamoxifen to the cytosol and microsomal fractions of several human breast tumors was investigated. By washing microsomal membranes with a KCl-free or a KCl-containing medium we could distinguish between intrinsic, extrinsic and contaminant estradiol binding sites in these membranes. We observed that treatment of the microsomes with low salt medium removes about 80% of the total estradiol binding sites, whereas 20% are not extractable. The concentration of unextractable [3H]estradiol binding sites in the microsomes varies in proportion to the level of cytosolic estrogen receptors (ER). About 10% of the total extranuclear specific estrogen binding sites was consistently found tightly associated to the microsomal fraction, which displays an affinity for estradiol (Kd = 0.1-0.6 nM) similar to that of the cytosolic ER. The displacement of [3H]estradiol with unlabeled hormone or with the antiestrogens, nafoxidine, enclomiphene and tamoxifen (TAM) exhibits identical IC50 values either in the cytosol or in the microsomal membranes. On the other hand, the microsomal fraction of breast tumors also binds [3H]hydroxyTAM, but with higher capacity and lower affinity than those of the cytosolic fraction. Furthermore, we did not observe correlation between the concentrations of ER and of antiestrogen binding sites (AEBS) in the tumors. These results indicate that microsomal membranes of human breast tumors contain estrogen binding sites which may be related to the cytosol ER recycling and that specific AEBS are predominantly localized in this membrane system. Furthermore, it is shown that the magnitude of estradiol binding to microsomes depends on the ER positive degree of the tumors, whereas the magnitude of the antiestrogen binding to the microsomes is independent of the ER status of the tumors. PMID- 1911425 TI - Aromatase activity in human adipose tissue stromal cells; the effect of fetal bovine serum fractions on dexamethasone-stimulated aromatization. AB - Aromatization in human adipose stromal cells is stimulated by dexamethasone, but only in the presence of fetal bovine serum (FBS). To determine whether there was a specific fraction of FBS responsible for this stimulation, FBS was fractionated either by a pressure-driven ultrafiltration membrane or by Sephadex gel filtration techniques. The stimulating factor(s) appeared to be in the FBS fraction of 150,000-300,000 Mw by Sephadex filtration. Conversely, FBS fractions with less than 30,000 Mw as separated by the former method inhibited the dexamethasone-stimulated aromatization of cultured adipose stromal cells. Bovine serum albumin, which constituted the major portion of FBS, had no discernible effect on the dexamethasone action on the aromatization of these cells. PMID- 1911426 TI - Methyl and bromo derivatives of estradiol are agonistic ligands for the estrogen receptor of MCF-7 breast cancer cells. AB - The binding affinity and relative estrogenic potency of 2-bromo-, 4-bromo-, 2 methyl- and 4-methylestradiol was evaluated in MCF-7 breast cancer cells. The relative binding affinities compared to estradiol were 47% for 2-methyl-, 25% for 4-methyl-, 37% for 4-bromo- and 17% for 2-bromoestradiol. However, both 2- and 4 methyl- as well as 2- and 4-bromoestradiol were able (a) to translocate the cytosolic estrogen receptor into the nucleus and (b) to induce the progesterone receptor in a concentration dependent manner. Finally, all ring-A substituted estrogens used in this study induced the pS2 mRNA as demonstrated by Northern blotting. From these findings we conclude that 2-bromo-, 4-bromo-, 2-methyl- and 4-methylestradiol are agonistic ligands for the estrogen receptor in MCF-7 breast cancer cells. PMID- 1911427 TI - Properties of a 4-ene-3-ketosteroid-5 alpha-reductase in cell extracts of the intestinal anaerobe, Eubacterium sp. strain 144. AB - When Eubacterium sp. 144 was grown in the presence of progesterone, extracts of these cells contained a 4-ene-3-ketosteroid-5 alpha-reductase (5 alpha reductase). No evidence for the presence of a 5 beta-steroid-reductase or a 5 alpha to 5 beta-steroid-isomerase was found. 5 alpha-Reductase activity was dependent on reduced methyl viologen as the electron donor and this could be generated biologically by adding pyruvate or H2 to cell extracts or chemically by adding sodium dithionite. NADH or NADPH with or without flavin nucleotides were not electron donors for 5 alpha-reductase. Most of the 5 alpha-reductase activity (60-65%) of crude extracts was located in the membrane fraction and the enzyme was solubilized by treatment with 1% Triton X-100. Optimum 5 alpha-reductase activity occurred at pH 7.0-7.5 in potassium phosphate buffer but was stimulated by Tris-HCl buffer (pH 8.0-9.0). 5 alpha-Reductase activity was highest at 10% (v/v) methanol and was progressively inhibited by higher methanol concentrations. Sulfhydryl reagents strongly inhibited 5 alpha-reductase but the enzyme was not affected by other metabolic inhibitors. Extracts prepared from cells induced with 16-dehydroprogesterone and grown without hemin contained 5 alpha-reductase and 16 dehydroprogesterone-reductase activities equivalent to those found in extracts of induced cells grown with hemin. This indicates that hemin is not required for the synthesis of active steroid double bond-reductases in strain 144. PMID- 1911428 TI - Gonadal endocrine dysfunction in patients with lung cancer: relation to responsiveness to chemotherapy, respiratory function and performance status. AB - Male lung cancer patients with poor performance status [Eastern Cooperative Oncology Group (ECOG) index 3-4] have an endocrinological dysfunction as assessed by serum testosterone and sex hormone-binding globulin (SHBG) levels. Patients who respond to therapy regain normal free testosterone levels within 12 weeks post chemotherapy, whereas non-responders continue to exhibit subnormal levels. The perturbations of endocrinological variables in patients with lung cancer is not due to development of hypoxia, as patients with respiratory failure maintain a significantly lower testosterone level compared to cancer patients. The development of a deficiency in total testosterone concentrations in lung cancer patients is correlated to their performance status, and not to the presence of metastatic disease. The mechanisms responsible for the endocrinological dysfunction in patients with lung cancer remain unknown. PMID- 1911430 TI - Testicular function in uremic rats: in vivo assessment of testosterone biogenesis. AB - The mechanism of testosterone (T) production defect in uremic rats has not yet been clearly defined and hypothalamo-hypophyseal impairment as well as primary testicular dysfunction have been suggested. In 42 rats followed monthly after subtotal nephrectomy up to 7.1 +/- 0.3 months, we observed a progressive significant decline of T and androstenedione (A) compared to control rats. Two months before the terminal phase of chronic renal failure (CRF), T/A ratio abruptly declined. T and its precursors on the 4-ene pathway, A, progesterone (P) and 17-hydroxyprogesterone were evaluated in pampiniform plexus testicular vein (PPTV) and in peripheral blood (PV) in end stage uremic rats (blood urea greater than 30 mmol/l, creatinine clearance less than 0.5 ml/min). Under basal conditions, all steroids but peripheral P were significantly lower in uremic rats than in controls as well as T/P and A/P ratios. After human chorionic gonadotropin (hCG) stimulation, T concentration in PV and PPTV remained highly significantly lower than in controls whereas T precursor concentrations were partially corrected by hCG administration. T/P ratio remained lower than in controls whereas A/P ratio was not significantly lower than in controls. Those data show a decline in all the steps of T biogenesis in uremic rats in basal conditions. The defect in 17 beta-hydroxysteroid dehydrogenase evidenced by T/A decrease at the end stage of CRF seems of primary testicular origin as it is not corrected by hCG administration as shown by T/P and A/P ratios in PPTV and in PV. PMID- 1911429 TI - Human placental estrogen synthetase (aromatase). Effect of environment on the kinetics of protein-protein and substrate-protein interactions and the production of 19-oxygenated androgen intermediates in the purified reconstituted cytochrome P450 enzyme system. AB - Estrogen synthetase (aromatase) catalyzes the conversion of androgen into estrogen via two hydroxylations at C19 and a subsequent C19-10 lyase reaction. We report here the results of a reconstitution study using a highly purified aromatase cytochrome P450 monooxygenase enzyme system, with both protein components (cytochrome P450 and NADPH-cytochrome P450 reductase) obtained from human term placental microsomes. By varying one of the components (amounts of cytochrome P450, NADPH-cytochrome P450 reductase, or androgen substrate) as the other two were held constant in four different environments (phospholipid, non ionic detergent, mixture of phospholipid and non-ionic detergent and buffer alone), we obtained evidence supporting the following conclusions. The reconstituted enzyme is more active and the protein components exhibit much lower apparent Km values in the detergent and/or lipid environment compared with buffer alone. Although the apparent Km and Vmax values for each aromatase protein component differ significantly in most cases with the particular limiting component and environment, the catalytic efficiency (Kcat/Km) was independent of the limiting protein component and varied with the environment only (highest in the lipid-detergent mixture and lowest in lipid alone). When the concentration of androgen substrate (androstenedione or testosterone) was varied at constant amounts of the aromatase protein components (NADPH-cytochrome P450 reductase saturating), the Km was lower and the Vmax was higher for adrostenedione. The specificity constant (Vmax/Km) was a function of the reconstitution environment (highest in lipid alone and lowest in detergent alone) and was, on average, about 4-fold higher for androstenedione in a particular environment. The extent of production of 19-oxygenated androgen intermediates (19-hydroxy and 19-oxo androstenedione) was examined at three different levels of aromatase cytochrome P450 (subsaturating, saturating, super-saturating) relative to the NADPH cytochrome P450 reductase component in the three different hydrophobic environments using androstenedione as substrate. Both 19-oxygenated androgens, each made in comparable amounts relative to control, were isolatable in greatest amounts under cytochrome P450 super-saturating conditions in the detergent-lipid mixed environment, and in least amounts under cytochrome P450 subsaturating conditions in the lipid-only environment. Based on these data, we propose that 19 oxygenated androgen intermediates are biosynthesized sequentially in a step-wise fashion as the cytochrome P450 and NADPH-cytochrome P450 reductase form transient complexes, and that the amount of isolatable 19-oxygenated androgen is proportional to the amount of excess cytochrome P450 component. PMID- 1911431 TI - Steroid profiles of brown adipose tissue. AB - In brown adipose tissue of alp-marmot (Marmota marmota), badger (Meles meles) and Wistar rats steroids of C21- and C19-type are identified and quantified. The detection of 3 alpha-hydroxy-5 alpha-pregnan-20-one, 3 alpha-hydroxy-5 beta pregnan-20-one, 3 alpha,21-dihydroxy-5 alpha-pregnan-20-one, 3 alpha,21-dihydroxy 5 beta-pregnan-20-one and 3 beta,21-dihydroxy-5 alpha-pregnan-20-one is of special interest since sleep-inducing properties have been described with these steroids. PMID- 1911433 TI - Evidence for colocalization of glucocorticoid receptor with cytoplasmic microtubules in human gingival fibroblasts, using two different monoclonal anti GR antibodies, confocal laser scanning microscopy and image analysis. AB - The cellular distribution of the glucocorticoid receptor (GR) in relation to the microtubule protein tubulin was studied in human gingival fibroblasts, using two different anti-GR antibodies of different Ig-classes, by indirect immunofluorescence immunocytology. Further studies were performed by confocal laser scanning microscopy and digital image analysis. The study focused on fluorochrome separation, optical sectioning, digital subtraction techniques and reconstruction of projections obtained using stacks of recorded transversal sections. The data presented further strengthens the notion of a structural colocalization between GR and cytoplasmic microtubules in human fibroblasts. PMID- 1911432 TI - Neither the endogenous nor a functional steroid hormone receptor binding site transactivate the ribosomal RNA gene promoter in vitro. AB - The mammalian ribosomal RNA gene promoters exhibit a conserved sequence between positions +1 and +16 that shows a high degree of homology to the response element for glucocorticoids and progestins (GRE/PRE). These sequences bind specifically the glucocorticoid receptor and the progesterone receptor (PR) albeit with lower affinity than a canonical GRE/PRE. Because steroid hormones are known to affect expression of the ribosomal genes, we tested the influence of hormone receptors on the activity of the ribosomal RNA gene promoter in a cell-free transcription assay. Preparations of PR that induce transcription from the mouse mammary tumour virus (MMTV) promoter do not stimulate but slightly inhibit transcription from the ribosomal RNA gene promoter. This weak negative effect is not mediated through binding to the hypothetical GRE/PRE as a mutant promoter that does not bind receptor is equally repressed. Introduction of the functional MMTV GRE/PRE upstream of the basal ribosomal RNA gene promoter does not enhance its transcription in the presence of an active PR. Thus, RNA polymerase I transcription cannot be stimulated in vitro by cis elements and regulatory proteins that are active in RNA polymerase II transcription. PMID- 1911434 TI - Hormone-associated variation of the glycan microheterogeneity pattern of human sex steroid-binding protein (hSBP). AB - hSBP is a steroid-binding protein (human) whose serum concentration is increased by estrogens and decreased by androgens. This regulation is independent of a direct effect on the hSBP gene transcription. The purpose of this work was to study the glycan microheterogeneous composition of the mature protein under physiological estrogen stimulation, by means of crossed affinoimmunoelectrophoresis using concanavalin-A. In men hSBP always divided into 2 fractions, both retarded. In women hSBP showed two other components, still more retarded. An explanation for these differences is given and the role of the glycan moiety of hSBP is discussed. PMID- 1911435 TI - A possible defect in the inter-conversion between cortisone and cortisol in prepubertal patients with congenital adrenal hyperplasia receiving cortisone acetate therapy. AB - Oral administration of cortisone acetate is widely used to treat prepubertal patients with congenital adrenal hyperplasia (CAH). However, efficient 'first pass' hepatic conversion of the biologically inactive cortisone (E) to cortisol (F) by the 11-reductase component of the 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) system is required for suppression of the hypothalamic-pituitary adrenal (HPA) axis. 11-beta-HSD activity can be assessed by measurement of urinary tetrahydroderivatives of E (tetrahydrocortisone, THE) and F (tetrahydrocortisol, THF), formed in separate hepatic compartments by reduction of the A ring. Inadequate HPA axis suppression is frequently encountered in peripubertal CAH patients receiving cortisone acetate therapy. In this paper, we describe THE and THF concentration in 24 h urine samples collected every 3-6 months from 14 prepubertal patients with simple virilizing CAH. The patients had been receiving cortisone acetate and 9 alpha-fluorohydrocortisone since diagnosis and were investigated for 2-4 years during which there was marked intra- and inter-individual variation in the level of suppression. Good and poor control of HPA axis suppression were defined on the basis of a profile of early morning serum 17-hydroxyprogesterone, androstenedione, plasma renin activity and 24 h urinary excretion of pregnanetriol, pregnanetriolone and 5 beta, 17 alpha hydroxypregnanolone. Serum steroids were measured by RIA and urinary metabolites quantitated as methyloxime-trimethylsilylimidazole derivatives by gas chromatography and GC-mass spectrometry. There were no significant differences in the THE/THF ratio between male (n = 9) and female (n = 5) patients during either good or poor therapeutic control. The data were therefore analyzed without consideration of patient sex. Urinary THE/THF (mean +/- SD) was significantly higher in patients during periods of poor control (6.56 +/- 2.51, P less than 0.001) compared with periods of good control (3.73 +/- 0.96) in the same patients. THE/THF levels were also significantly (P less than 0.001) higher in CAH patients, irrespective of the level of control, than those for the normal subjects (1.79 +/- 0.20). Furthermore, THE excretion was significantly higher during periods of poor control compared with good control at all doses of cortisone acetate administered (10-50 mg/day). There were no significant differences in THF excretion. THE levels also rose significantly (P less than 0.001) in response to increasing total dose during periods of poor control. The increase in THF excretion was slight and significant only at doses greater than 40 mg/day compared with doses less than 15 mg/day.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1911436 TI - Analysis of coenzyme binding by human placental 3 beta-hydroxy-5-ene-steroid dehydrogenase and steroid 5----4-ene-isomerase using 5'-[p (fluorosulfonyl)benzoyl]adenosine, an affinity labeling cofactor analog. AB - 3 beta-Hydroxy-5-ene-steroid dehydrogenase and steroid 5----4-ene-isomerase copurify as a single, homogeneous protein from human placental microsomes. Affinity alkylation with 2 alpha-bromoacetoxyprogesterone suggests that the dehydrogenase and isomerase substrate steroids bind at different sites on the same protein. However, the coenzyme, NADH, completely abolishes the alkylation of both enzyme activities by the progestin analog [Thomas J .L., Myers R. P., Rosik L. O. and Strickler R. C., J. Steroid Biochem. 36 (1990) 117-123]. Unlike bacterial 3-keto-5-ene-steroid isomerase, the human isomerase reaction is stimulated by diphosphopyridine nucleotides (NADH, NAD+). The affinity labeling nucleotide analog, 5'-[p-(fluorosulfonyl)benzoyl]adenosine (FSA), inactivates the dehydrogenase and isomerase activities at similar rates in an irreversible manner which follows first order kinetics with respect to both time and alkylator concentration (0.2-0.6 mM). FSA is a cofactor site-directed reagent that binds with similar affinity as a competitive inhibitor of NAD+ reduction by dehydrogenase (Ki = 162 microM) or as a stimulator of isomerase (Km = 153 microM). Parallel plots derived from Kitz and Wilson analysis indicate that FSA inactivates the two enzyme activities with equal alkylation efficiency (k3/Ki = 1/slope = 0.51/mol-s for both). The 3 beta-hydroxysteroid substrate, pregnenolone, protects isomerase as well as dehydrogenase from inactivation by FSA. These observations are evidence for a single cofactor binding region which services both enzyme activities. PMID- 1911437 TI - Expression of rat 5 alpha-reductase in Saccharomyces cerevisiae. AB - Dihydrotestosterone (DHT) is the principle androgen in certain tissues such as the prostate. DHT is formed from testosterone by the NADPH-dependent enzyme 5 alpha-reductase (5AR). In this paper we report the expression of catalytically active steroid 5AR from the rat in Saccharomyces cerevisiae. A full length cDNA coding for 5AR was isolated from a rat liver cDNA library and fixed in frame to the signal sequence of yeast acid phosphatase. A constitutive short promoter fragment of the acid phosphatase gene (PHO5) and the PHO5 transcriptional terminator were added and the expression cassette ligated into the yeast 2 mu vector pDP34. S. cerevisiae transformed with the 5AR expression plasmid pDP34/PHO5AR exhibited about 100-fold more activity per gram wet weight than rat prostate. PMID- 1911438 TI - Inhibition of estrone sulfatase enzyme in human placenta and human breast carcinoma. AB - Estrone sulfatase is an important mechanism of local synthesis of biologically active estrogens in human breast cancer. The human placental microsome and breast carcinoma mitochondrial/microsomal estrone sulfatase activity were characterized and inhibition studies performed. The Km of the placental tissue enzyme was 6.83 microM, Vmax 0.015 nmol/min/mg, and for the breast carcinoma tissue Km was 8.91 microM and Vmax 0.022 nmol/min/mg. Danazol produced a significant inhibition of estrone sulfatase (20% with 50 microM danazol). No significant inhibition was seen in the presence of aminoglutethimide, rogletimide, tamoxifen, 4 hydroxyandrostenedione, stilboestrol, or any metabolites of danazol or tamoxifen. Studies with synthetic and naturally occurring steroids demonstrated that the presence of a sulfate group at the 3 position to be the most important factor in determining inhibition, and the most potent inhibitor was 5 alpha-androstene-3 beta,17 beta-diol-3-sulfate (Ki of 2.0 microM). The naturally occurring 3 sulfated steroids all demonstrated competitive inhibition. These studies could form the basis for the design of a potent estrone sulfatase inhibitor which would have potential therapeutic activity in the management of breast cancer. PMID- 1911439 TI - Estradiol and progesterone effects on relative luteinizing hormone and follicle stimulating hormone release induced from superfused anterior pituitary cell cultures by defined LHRH pulse regimens. AB - These studies examined the capacity of estradiol and progesterone to modulate relative luteinizing hormone (LH) and follicle stimulating hormone (FSH) secretion from superfused anterior pituitary cells when stimulated with luteinizing hormone releasing hormone (LHRH) pulse regimens of specific amplitude, duration and frequency. There was particular interest in whether such steroid and LHRH treatments induced evidence of divergent LH or FSH secretion. Pituitaries were recovered from adult, 2 week ovariectomized rats and cultured for 48 h with collagen coated Cytodex microcarrier beads. Cultures were preincubated either with or without estradiol (1 or 10 nM) for 48 h and were subsequently incubated for 3,6 or 12 h with 100 nM progesterone. All groups were then pulsed with 1 of 3 LHRH regimens; regimen 1 delivered 8 ng in a single 100 microliters bolus once/h; regimen 2 divided the 8 ng dose of regimen 1 into 3 equal doses administered at 4 min intervals thereby maintaining the 8 ng mass of regimen 1 while extending the duration of exposure; regimen 3 was the same as regimen 2 except that the 3 equal doses were administered at a pulse frequency of 1 per 2 h rather than 1 per h thereby not only maintaining the duration of exposure as in regimen 2 but also reducing the pulse frequency. 1 nM estrogen alone for 48 h had no effect on LHRH stimulated LH release regardless of regimen; however, FSH was increased when hourly pulses of increased duration were applied (regimen 2). When estrogen was increased to 10 nM, regardless of regimen, LH was predominantly inhibited while FSH was unaffected. When 1 nM estrogen was followed by progesterone, both LH and FSH were elevated at 6 h progesterone in response to regimen 2; with 10 nM estrogen however, a divergent response was observed in that LH release was elevated at 6 h while FSH was elevated at 3 h in response to regimens 2 and 3. These results first of all confirm that progesterone in combination with estrogen is capable of exerting both inhibitory and stimulatory effects on gonadotropin secretion; secondly, these studies show that, as a direct pituitary effect, the LHRH regimen and the gonadal steroid milieu are capable of interacting to significantly influence the relative secretion of LH and FSH. The data therefore suggest that the divergent gonadotropin secretion seen in various physiological states in vivo is due likely in part to a combination of estrogen and progesterone priming in combination with the hypothalamic LHRH secretory pattern. PMID- 1911440 TI - Stimulation of in vitro ovarian estradiol-17 beta synthesis in the rainbow trout by the carbohydrate-poor protein fraction from sockeye salmon pituitary glands. AB - The role of carbohydrate-poor (Con A I) and carbohydrate-rich (Con A II) pituitary protein fractions, isolated from sockeye salmon (Oncorhynchus nerka), were investigated pertaining to in vitro estradiol-17 beta (E2) production by rainbow trout (Oncorhynchus mykiss) ovarian follicles. During the early vitellogenic phase of the reproductive cycle, using defolliculated ovarian follicle preparations (outer epithelium-thecal layer absent), it was demonstrated that the Con A I fraction was capable of increasing E2 production, in the presence of exogenous testosterone (T) as the substrate. Under similar conditions the Con A II fraction (containing the maturational gonadotropin) was inactive. However the Con A II fraction or T, separately, increased E2 production by intact ovarian follicles, whereas the Con A I fraction did not. A mechanism proposed to explain the regulation of ovarian E2 synthesis involves the Con A I fraction enhancing aromatase activity in granulosa cells permitting an increased conversion of T to E2. PMID- 1911441 TI - Evolution of immunoreactivity of monoclonal antibodies H222 and/or D547 used in the detection of breast cancer estrogen receptors. Varying reactivity of receptor isoforms. AB - From 1984 to 1990, human breast cancer estrogen receptors have been measured both by a radioligand assay (RLA[3H]estradiol) and by an enzyme immunoassay (Abbott ER EIA kit). The ratio EIA/RLA results increased continuously from 1.04 (1984) to 1.87 (1990), and this evolution was consistent with the last trial of the E.O.R.T.C. receptor study group (Trial 1989-II, EIA/RLA = 2.5). Dilution studies of cytosols with the current ER-EIA kits showed an important parallelism defect of the standard curve, the final result of cytosols (fmol/mg protein) obtained from the upper part of the curve (between 100 and 500 fmol/ml) being 1.5 to 2 times higher than the results obtained from readings of the lower part of the standard curve (between 0 and 50 fmol/ml). Chromatographic experiments were carried out during 1986 and the measures of binding sites by RLA and of immunoreactive sites by EIA on chromatographic fractions were compared. Identical results were obtained with EIA and RLA, either on polymeric forms of the estrogen receptor, or on monomeric forms obtained after dissociation by 0.4 M KCl. The same experiments performed during 1990 showed that, in the chromatographic fractions, the concentration of immunoreactive sites was twice as large as that of ligand-binding sites, detected by tritiated estradiol. Furthermore, the detection of polymeric and monomeric receptor isoforms by monoclonal antibodies varied, and was increased by the presence of KCl (0.4 M) and/or bovine serum albumin (BSA) (1 mg/ml) in the cytosol. These findings showed that the large differences between enzyme immunoassay and ligand-binding assay results currently observed were due to differential reactivity of monoclonal antibodies for the estrogen receptor standard provided in the ER-EIA kits and for the estrogen receptor present in cytosols from human breast cancers, suggesting modifications of immunoreactivity of the monoclonal antibodies actually provided in the ER-EIA kits. PMID- 1911442 TI - Metabolism of the oral contraceptive steroids ethynylestradiol and norgestimate by normal (Huma 7) and malignant (MCF-7 and ZR-75-1) human breast cells in culture. AB - Human breast cancer cells are used extensively for the study of steroid hormone action. It is known that in both receptor positive and receptor negative cell lines there is considerable metabolism of the natural estrogens, estradiol (E2) and estrone (E1) with interconversion of the two steroids and formation of sulphate and glucuronide conjugates. The aim of the present work was to see if the commonly used oral contraceptive steroids (OCS) ethynylestradiol (EE2) and norgestimate (Ngmate) were metabolized in human breast cancer cell lines (MCF-7 and ZR-75-1) and a normal breast cell line (Huma 7). MCF-7, ZR-75-1 and Huma 7 cells were maintained in Dulbeccos Modified Eagles Medium (DMEM) containing foetal calf serum (FCS) insulin and hydrocortisone. In addition, ZR-75-1 cells required epidermal growth factor (EGF) and E2 while MCF-7 cells required only EGF. On reaching confluence cells were transferred to DMEM containing charcoal stripped FCS, insulin and hydrocortisone. 48 h later this medium was renewed, radiolabelled steroid ([3H]E1; [3H]E2; [3H]EE2, [3H]Ngmate; [3H]E1-SO4; 1 nM; 0.2 microCi) was added and incubation was for 24 or 48 h. Following incubation, the medium was removed and radioactive steroid extracted with ether. Metabolites were analysed by on-line radiometric HPLC. All the cell lines were able to interconvert E1 and E2; the equilibrium favouring the formation of E2 in MCF-7 and ZR-75-1 and E1 in Huma 7 cells. E1 and E2 also underwent phase II metabolism to form their respective estrogen sulphates, this activity being most marked in the Huma 7 cell line. In addition to sulphotransferase activity, the study with E1 sulphate demonstrated sulphatase activity in both normal and cancer cells. There appeared to be no difference in extent of hydrolysis, with both E1 and E2 formed. With EE2 as substrate there was no evidence of phase I metabolism in any of the cell lines but there was conversion to the presumed 3-sulphate conjugate. The percentage formation of this metabolite was very much greater in Human 7 cells (64.1 +/- 9.6% after 24 h) than in MCF-7 and ZR-75-1 cells (7.4 +/- 5.3% and 10.6 +/- 4.1%, respectively after 24 h). In all the cell lines deacetylation of the progestogen Ngmate to norgestrel oxime was complete within 24 h. In addition there was evidence of loss of the oxime moiety to give norgestrel.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1911443 TI - Perio-prosthetic management in restoring teeth with reduced clinical crown in children. AB - The purpose of this article is to underline the importance and to discuss the indications and techniques of crown lengthening procedures prior to prosthetic treatment of mutilated or undererupted permanent teeth of children. The aim of surgical crown lengthening is the exposure of at least 3 to 4 mm of healthy tooth structure coronally to the alveolar crest, length that will allow the formation of the new epithelial attachment and the existence of 1 to 2mm of tooth structure for the construction of a biologically acceptable crown margin. If the margin of the defect is inadequate distance from the alveolar crest the surgical procedure involves reduction of the attachment complex and is limited to the soft tissues only (a gingivectomy, apically repositioned full thickness flap, distal wedge). When the margin of the defect is close to the alveolar crest, less than 3 mm, the surgery involves also modification of the hard tissues of the periodontium (apically repositioned full thickness flap with ostectomy-osteoplasty). Although cases of children generally call for a conservative approach, the necessity for harmony between restorative procedures and materials with the supporting structures make surgical intervention inevitable. PMID- 1911444 TI - Aragao's function regulator, the stomatognathic system and postural changes in children. AB - Normalization and regulation of the stomatognathic system and whole-body postural changes were observed in five class II division 1 and open bite patients. All five patients had a history of nasal breathing difficulties, lip incompetence and abnormal whole-body posture. PMID- 1911445 TI - Two year longitudinal study of the fluctuation of clinical signs of TMJ dysfunction in Japanese adolescents. AB - Signs of TMJ dysfunction syndrome were monitored longitudinally from the age of 12 to 14 years in 160 junior high students and 15 to 17 years in 480 senior high school students. Thirty-one percent of the junior high school students and 39.6% of the senior high school students presented with one or multiple signs of TMJ dysfunction syndrome at least once during the examination period. The percentage of subjects presenting continuously with one or multiple signs at all examinations was 8.9% among junior high school students and 12.9% among senior high school students. The predominant sign in the subjects, who continuously presented with one or multiple signs of TMJ dysfunction syndrome was TMJ sounds. The number of subjects presenting with TMJ clinical signs for the first time at the third examination (third year student) was high compared to the other examinations. When intra-individual longitudinal results were examined in subjects, who at least once during the examination period presented with one or multiple signs of TMJ dysfunction syndrome was found to be high (75.0% among junior high school students and 86.5% among senior high school students). In the subjects presenting with one or multiple signs of TMJ dysfunction syndrome continuously over the two year period, the percentage of subjects, who at least once presented with multiple signs was 90.9% among junior high school students and 22.0% among senior high school students. PMID- 1911446 TI - Agenesis of the permanent lateral incisor: distribution, number and sites. AB - Agenesis of the lateral incisor was examined in 112 patients (42 males and 70 females). The distribution of this condition was assessed according to site, symmetry of the anomaly and the number missing for both males and females. Hypodontia of both maxillary lateral incisors was the most common form of agenesis recorded, with the absence of lateral incisors in the maxilla occurring in 91 per cent of the sample studied. Hypodontia in the maxilla was recorded more frequently in females (61 subjects) than in males (30 subjects) at a ratio of 2:1 respectively. Absence of lower lateral incisors was rare. PMID- 1911447 TI - Dens evaginatus--a difficult diagnostic problem? AB - Dens evaginatus may pose a problem, on occasion, in diagnosis and treatment planning. This paper presents a case report indicating such difficulties and suitable treatment measures. PMID- 1911448 TI - Traumatic avulsion of the mandibular right primary lateral incisor and cuspid. AB - Premature loss of the primary mandibular cuspid has been considered rare. When this occurs, however, space maintenance should be considered to prevent distal drifting of the lateral incisor. The purpose of this case report was to document traumatic avulsion of the mandibular right lateral and cuspid. A lingual arch appliance with a spur was fabricated to maintain space and prevent movement of the mandibular incisors. Sequelae of premature loss of primary teeth is presented. PMID- 1911449 TI - Natal and neonatal teeth: a clinical and histological study. AB - Nine thousand and six hundred infants delivered in a maternity hospital were examined for the prevalence of natal and neonatal teeth. The prevalence among this group was noted. The teeth were the normal primary incisors that had erupted prematurely. The crown was normal in shape and size with very little root formation. The histological features were that of an immature tooth. PMID- 1911450 TI - Empiric therapy for febrile granulocytopenic patients: no longer a challenge? PMID- 1911451 TI - Zurich experience in osteogenic sarcoma: state of the art--past, present or future? PMID- 1911452 TI - Meta-analysis: the fashion of summing-up evidence. Part I. Rationale and conduct. AB - Meta-analysis is the process of formally combining the quantitative results of separate studies in order to increase the statistical precession of estimated effects. It has become fashionable when individual studies fail to yield conclusive results. A recent update of a meta-analysis (overview) for treatments of patients with early breast cancer motivated this commentary to discuss the rationale, principles of conduct, statistical methods, and graphical display for summing up results. In part II we will approach the issue of interpretation and use of overview data. PMID- 1911453 TI - Clinical relevance of biochemical modulation of 5-fluorouracil. AB - Biochemical modulation is a special type of combination chemotherapy which aims to selectively improve the therapeutic index by increasing the antitumor effect and protecting against toxic side effects. Biochemical modulation seems to be an attractive way to circumvent quantitative and qualitative heterogeneity of tumors. In the past decade a number of biochemical modulation approaches have been tested to improve the activity of 5-fluorouracil (5FU). 5FU itself has only modest anticancer activity but has been shown to be a very attractive target for biochemical modulation. A number of the combinations have been ineffective in the clinic despite extensive testing in a number of schedules. Some other combinations were initially tested in an inappropriate schedule, but were active when applied in another schedule. The latter was made possible by a systematic preclinical development of combinations with a proper translation to the clinic accompanied by pharmacodynamic evaluation. This review describes a number of biochemical modulation combinations, both inactive and active. The main conclusion is that properly applied biochemical modulation schedules may lead to successful use in the clinic. PMID- 1911454 TI - Prolonged adjuvant tamoxifen: a beginning not the end. PMID- 1911455 TI - Home treatment of febrile neutropenia: an empirical oral antibiotic regimen. AB - Between May 1988 and November 1989, 68 consecutive febrile courses supervening after polychemotherapy for lymphoma outpatients (median age 50 years) were treated by the combination of oral Pefloxacin/Amoxicillin Clavulanic acid. In terms of median data, neutropenia appeared on d9 [d1-d17], and lasted 5 days [2 9] with a PMN nadir observed at 0.104 x 10(9) [0-0.5 x 10(9)/l], while fever rose on d10 [1-24]. In 59 cases (87%), fever and/or focal symptoms disappeared within 3 days, after which treatment was maintained for 7 days. Nine failures were observed, of which 2 were due to abandonment of treatment, 2 to vomiting and 5 to persistence of the original symptoms. Meti Susceptible-Staphylococci were found in blood samples from 2 patients, one of whom, with grade IV lymphoma that had proved resistant to chemotherapy, died. The treatment was found to be effective and well tolerated, offering a good alternative to hospitalization during a transient chemotherapy-induced neutropenia. PMID- 1911456 TI - Zurich experience with preoperative, high dose methotrexate-containing chemotherapy in patients with extremity osteosarcomas (OSA). AB - From 1979 to 1990, 37 patients with extremity osteosarcomas, 22 of them males and 15 females, median age 19 years, received pre- and postoperative chemotherapy. The period of observation, calculated from after the primary operation, ranged from 1-114 months, median 25 months. After preoperative chemotherapy, 9 (24%) underwent a primary amputation, in 28 (76%) a limb salvage procedure was possible, 4/29 (14%) later developed local recurrences, metastases were diagnosed in 8/9 amputees and 5/28 after limb-sparing surgery. The five-year disease-free and overall survivals after amputation are 11% and 33%, respectively, compared to 68% and 75%, respectively (p = 0.001 and 0.018, respectively, for long rank). Results of histologic assessment after preoperative chemotherapy are of significant prognostic impact. The earlier prognostic groups of 0%-49% necrosis versus 50%-100% necrosis were statistically no longer suitable for distinguishing useful prognostic groups. In this second analysis, patients with 0%-79% necrosis versus 80%-100% necrosis had 5-year disease-free survivals of 81% versus 44% (p = 0.032) and 5-year overall survivals of 88% In summary, 24% of our patients with extremity osteosarcomas, most of them with large primaries close to joints, had to undergo primary amputation and had only a 33% 5-yr-survival, whereas limb salvage procedures with pre-and postoperative chemotherapy were associated with a 5-yr survival of 75% and thus had no adverse impact. Careful selection of patients for successful management of osteosarcomas is important; necrosis of 80% and more after preoperative chemotherapy is a prerequisite for a favourable outcome. PMID- 1911457 TI - Non-Hodgkin's lymphoma arising in skeletal muscle. AB - Four patients with non-Hodgkin's lymphoma who presented with clinical enlargement of muscle are reported. In three patients the only site of disease was muscle. Two patients with involvement of the paraspinal muscles demonstrated neurological complications due to spinal nerve root entrapment. A review of the literature emphasises the rarity of primary muscle lymphoma and suggests that disease arising at this site may confer a poor prognosis. PMID- 1911458 TI - Treatment of relapsed Hodgkin's disease using a weekly chemotherapy of short duration: results of a pilot study in 20 patients. AB - Twenty patients with relapsed Hodgkin's disease have been treated with a weekly regimen of chemotherapy (VAPEC-B) comprising Adriamycin 35 mg/m2 i.v. weeks 1, 3, 5, 7, 9, 11; cyclophosphamide 350 mg/m2 i.v. weeks 1, 5, 9; etoposide 100 mg/m2 p.o. daily for 5 days, weeks 3, 7, 11; vincristine 1.4 mg/m2 i.v. weeks 2, 4, 6, 8, 10; bleomycin 10 mg/m2 i.v. weeks 2, 6, 10 and prednisolone 50 mg p.o. daily weeks 1-5, 25 mg p.o. daily weeks 6-11. All had previously received an Adriamycin containing combination and in nine cases this was for relapse following MVPP. In all but one case relapse occurred less than one year after the completion of previous treatment and in 14 cases, disease recurred within 24 weeks. Thirteen patients had extra-nodal involvement. Following six weeks of treatment 14 patients had responded (6 CR; 4 CR, uncertain; 4 PR), four had stable disease, one had progressed and one had died of sepsis. Fourteen patients proceeded to high dose cyclophosphamide and BCNU with autologous bone marrow rescue and seven of these are progression free between 4 and 156 weeks later. High dose therapy was not possible in five patients, three of whom achieved CR. Of these, two (one with bulky nodal disease and skin infiltration; one with extensive bone marrow involvement) are alive and relapse free without further treatment at 95 and 114 weeks. Overall, the regimen was well tolerated but haematological toxicity was moderate or severe in ten patients and four were admitted to hospital for treatment of suspected or confirmed septicaemia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1911459 TI - The relationship of spousal caregiver burden to patient disease and treatment related conditions. AB - The prevalence and intensity of different caregiving burdens experienced by spousal caregivers and the association of these burdens with various patient illness and treatment-related conditions were examined in a sample of 295 married cancer patients and their spouses. The spousal caregivers were confronted with a wide range of burdens associated with their caregiving responsibilities. Objective, as compared to subjective, caregiver burdens were more strongly associated with patient disease and treatment-related conditions. Compared to husbands, wives experienced more burden and these burdens were more strongly associated with the various disease and treatment conditions. PMID- 1911460 TI - Antiemetic efficacy of cimetidine randomized, double-blind, crossover study with dexamethasone in cancer patients receiving emetogenic chemotherapy. AB - In a randomized, double-blind, crossover study the antiemetic effect of cimetidine was compared with that of dexamethasone in cancer patients receiving emetogenic chemotherapy. Thirty-two patients were evaluable and all were chemotherapy-naive. Eight patients (25%) received high doses of cisplatin, 17 (53%) had cyclophosphamide in combination treatment, 2 (6%) received adriamycin, and 1 another chemotherapy of less emetogenic potential. Complete protection (CR) rates of 59.4% and 62.5% were achieved with cimetidine and dexamethasone, respectively. In addition, three (9.4%) and 1 (3%) patients attained partial protection with cimetidine and dexamethasone, respectively. No significant difference was noted between the two antiemetic therapies (p = 0.07). Although CR has not been achieved in any of those patients who received cisplatin, a comparable antiemetic effect was attained. Both antiemetic regimens were well tolerated with minimal side effects. We conclude that the antiemetic potential of cimetidine and its safety deserve further investigation in a larger study, perhaps in combination with other antiemetic agents. PMID- 1911461 TI - Continuous infusion 5-fluorouracil, etoposide and cis-diamminedichloroplatinum in patients with metastatic carcinoma of unknown primary origin. AB - We conducted a phase II clinical trial of 5-fluorouracil (5 day continuous infusion), cis-diamminedichloroplatinum and etoposide in previously untreated patients with metastatic carcinoma of unknown primary origin. Of the thirty-six evaluable patients (21 adenocarcinoma, 14 undifferentiated carcinoma and 1 squamous cell carcinoma), eight patients responded to this treatment (4 CR, 4 PR). Responses were seen in both soft tissue and visceral disease. Toxicity was significant and included grade III/IV myelosuppression in over 90% of patients treated. Non-hematologic toxicity included nausea/vomiting and stomatitis. Although the remissions obtained in this study appear to be durable (median duration of complete remission greater than 24 months), the regimen does not appear to offer significant advantages over other less toxic and more easily administered cisplatin-based combinations. PMID- 1911462 TI - Inefficiency of cisplatin plus 5-FU as second-or third line treatment in advanced breast cancer. PMID- 1911463 TI - Ewing's sarcoma in the second cervical vertebra. PMID- 1911464 TI - Response to high dose cyclophosphamide with GM-CSF in Merkel cell tumor. PMID- 1911465 TI - Review of the professional group meeting on biological time series signals and their fluctuations. PMID- 1911466 TI - An overview of biological signal processing: non-linear and non-stationary aspects. AB - The elucidation of biological systems will be one of great keys to scientific advance. However, it is difficult to analyze such biological systems because of their non-linear and non-stationary characteristics. This paper reviews newly developed methods for analysing such non-linear and non-stationary characteristics. PMID- 1911467 TI - Fluctuations of biological rhythm. AB - A biological body is a soft system as compared with an ordinary mechanical system, and hence it is more reasonable that phenomena occurring in a biological body are not steady but fluctuating. A common rule can be found in various biological fluctuations. PMID- 1911468 TI - Fluctuations observed in biological time series signals and their functional significance. AB - Fluctuation phenomena in a single neuronal spike train of a cat were investigated during sleep states. Although white-noise-like fluctuations were observed during non-REM sleep, they became 1/f fluctuations during REM sleep. REM sleep is regarded as a reversion to a state of the fetal brain. The functional significance of 1/f fluctuations in biological time series signals is discussed from the viewpoint of homeostasis. PMID- 1911469 TI - Low frequency components of the body's center of gravity and blood circulation. AB - The purpose of this study was to clarify how low frequency components of the body's center of gravity, mainly 1 minute waves (1-MWs), are related to the mechanism of compensation for the venous blood pooling in the legs during static standing in humans. The 1-MWs of foot pressure center, oscillations of body circumferences and other parameters were analyzed with cross-power spectral analysis. The 1-MW of the calf's blood volume propagated to the chest via the venous system. This was inversely synchronized with the 1-MW of the body's center of gravity. It was speculated that muscular pumping of the calf related to the 1 MW of the body's center of gravity might be compensating for the venous blood pooling in the legs. PMID- 1911470 TI - Why do we compute the spectra? AB - Mechanisms underlying biological phenomena are often understood on the basis of equivalent electric circuits. An effective way of probing a biological system is to measure a signal which is a reflection of the phenomena and to analyze it according to the conventional recipe, for instance, the spectrum analysis. In this paper the meaning of spectrum analysis of a biological signal is briefly discussed in connection with linear system identification. Wiener analysis of a non-linear system is also mentioned. PMID- 1911471 TI - Bi-spectral analysis of bioelectric phenomena: a survey. AB - This article presents five examples of bi-spectral analysis of bioelectric phenomena which show non-Gaussian statistics. Examples include: analysis of the electroencephalogram (EEG), electrical response of retinal horizontal cells to light stimuli, the evoked potential (EVP), the electromyogram (EMG) and spontaneous synaptic potentials (SSP). Readers may find the higher-order spectral analysis useful in extracting information underlying various kinds of bioelectric phenomena. PMID- 1911472 TI - Ventilatory effects of percutaneous magnetophrenic stimulation. AB - This study was conducted with the purpose of elucidating the ventilatory effect of percutaneous magnetic stimulation of the phrenic nerve and investigating the possibility of clinically utilizing this effect as the mechanism of an artificial respirator. A magnetic stimulator consisting of a flat circular coil generating strong magnetic fields up to a maximum of 1.3 Tesla was developed. Formed from 1.8 mm diameter copper wire, this coil is 40 mm in diameter, 14 mm in thickness and has an inductance of 24 microH. The appurtenant current generator can deliver more than 5000 A to the coil. The capacitor terminal voltage (Vc) of the generator was used as a parameter of the intensity of the stimulus. Ventilatory effects were assessed mainly by diaphragmatic electromyogram and by transdiaphragmatic pressure, ventilation flow and tidal volume measurements. Magnetic stimulation was applied percutaneously to a unilateral phrenic nerve in dogs as well as human subjects and also to a median nerve of the forearm in human subjects. The range of stimulatory intensity Vc necessary to obtain ventilatory effects was 400-500 V, and the tidal volume thus obtained corresponded to normal breathing at rest for both dogs and humans. No pain was felt in the vicinity of point of application of the stimulator and there were no significant adverse effects such as changes in the ECG or heart rate. These results indicated that percutaneous magnetic stimulation of the phrenic nerve could produce adequate ventilatory effects in control applications. PMID- 1911473 TI - Long term variceal sclerotherapy: is endoscopic sclerosis a unique therapeutic approach and a true alternative to surgery? AB - Endoscopic sclerotherapy has been used to control acute variceal haemorrhage which persists despite conservative therapy, prevent recurrent variceal haemorrhage in patients with a history of oesophageal haemorrhage, and to prevent a haemorrhage in patients with oesophageal varices who never bled. In this short paper I will cover our personal experience with more than 2000 patients receiving particularly paravariceal endoscopic sclerotherapy of bleeding esophageal varices, and especially present the results of our prospective and controlled randomized trials (Table 1) and underline the thesis that endoscopic sclerotherapy and surgical procedures for patients with portal hypertension are complementary supporting measures or options. PMID- 1911474 TI - The current role of decompressive shunts and liver transplant in portal hypertension. AB - Based on our current management of many patients with variceal bleeding and the availability of all treatment options at our institution, the algorithm of management given in Figure 3 has evolved PMID- 1911475 TI - Devascularization and transection procedures. AB - Transection and devascularization procedures have been by far the most popular operations for the treatment of oesophagogastric varices in Japan during the last two decades and although since the new development of endoscopic sclerotherapy during the last ten years the number of patients treated by operation has decreased considerably, these procedures still remain the treatment of choice in many of the surgical institutions in Japan, especially in good-risk patients with oesophagogastric varices. PMID- 1911476 TI - Blunt liver trauma at sunnybrook Medical Centre: a 13 year experience. AB - Between June 1, 1976 and June 30, 1989 The Regional Trauma Unit at Sunnybrook Medical Centre in Toronto, Ontario, Canada received 3730 patients. Of these 335 (9%) sustained a liver injury, 95% being due to blunt trauma. Open peritoneal lavage was performed on 80% of liver trauma patients (267/335), 99% being true positive. A laparotomy was performed on 97% of patients (324/335). Major surgical treatment was required in 132 patients (41%) and minor treatment in 192 patients (59%). The remaining 11 patients were treated conservatively (n = 3) or died during resuscitation (n = 8). Morbidity directly related to the liver injury was seen in 29 of 249 surviving patients (11%) although overall morbidity was 27% (67/249). Reoperation was required in 6% (14/249) with abscess or hematoma accounting for 11 of 14 operations. The overall mortality rate was 26% (86/335). Eighty two percent of patients (n = 276) had a grade I, II or III liver trauma according to Moore's classification with a mortality of 12% (n = 32). The remaining 18% of patients (n = 59) had a grade IV or V liver trauma with a mortality of 44% (n = 26). Of the 86 deaths, head injury accounted for 48 (56% of deaths); liver hemorrhage for 17 (20%), liver sepsis for 1 (1%) and other causes for 20 deaths (23%). Thus death due to the liver injury itself (hemorrhage and sepsis) occurred in 18 out of 335 patients (5% overall). Head injury accounted for the death of 48 out of 335 patients (14% overall). Over the past 13 years a trend has occurred at our institution whereby we are seeing less liver trauma in our population of multiply injured patients from 12% (1976-1983) down to 7% (1985 1989); with a gradual decline in overall mortality from 32% (1976-1983) to 19% (1985-1989), whereas the percentage of deaths due to head injuries and liver injury have increased. PMID- 1911477 TI - Long-term management after variceal bleed--the current role of sclerotherapy. AB - While injection sclerotherapy has been accepted as the treatment of choice for acute variceal bleeding, its role as a definitive long-term treatment modality has not yet been clearly defined. This paper will critically analyse the current status of this technique, now widely used, and a comparison will be made with conventional medical management. The review will be based on the 10 years' Cape Town experience and the published series on this subject. A long-term management strategy will also be discussed. PMID- 1911478 TI - Hydatid disease of the liver. Diagnosis and surgical treatment. AB - A series of 155 cases of hepatic hydatid disease, occurring in 121 patients, were operated on at the Naval and Veterans Hospital of Athens. Ultrasonography and computerized axial tomography provided the preoperative diagnosis in 89 and 93 percent of the cases respectively in recent years. Thirty one percent of the cases presented with complications, the commonest of these being infection of the cyst (10 percent) and rupture of the cyst into the bile ducts (17 percent). Total cystectomy was performed in three cases and removal of the endocyst with its content in the remaining 152. The remaining cavity was either externally drained (57 cases), or filled with omentum (omentoplasty--95 cases). External fistula and infection of the residual cavity occurred in 32 and 56 percent after simple drainage and in 4 and 2 percent respectively after omentoplasty. Differences are statistically significant (p less than 0.001). Hospitalization was also significantly longer after drainage than after omentoplasty (p less than 0.01). Obstructive jaundice after intrabiliary rupture of the cyst was more successfully managed after additional choledochoduodenostomy than after simple drainage of the common bile duct. Intrapericoneal recurrence of hydatid disease occurred in two cases. The conclusion of the present study is, that ultrasonography and computerized axial tomography provide an acceptable rate in the diagnosis and that omentoplasty offers a very low complication rate in the management of hydatid cystic disease of the liver. PMID- 1911479 TI - Surgical treatment of giant cavernous hemangioma liver. AB - In the past five years, 16 adults (10 females, age 25-61 years, mean 48) with giant cavernous hemangioma of the liver measuring 15-31 cm (mean-19) underwent surgery in a single Institution. Diagnosis was made with the help of multimodal investigations- ultrasound (US), computed tomography (CT), hepatic angiography, hepatic scintigraphy and fine needle biopsy. Ultrasound and CT had sensitivities of 69% and 82% respectively. Fourteen had preoperative selective hepatic artery embolization to study its effect on operative blood loss. Indication for surgery in all cases was a large abdominal mass with varying severity of pain. In addition, 5 had hemetological and/or coagulation abnormalities, hemobilia in 1 and pyrexia in 1. Seven left lobectomies, 3 left lateral segmentectomies, 2 right lobectomies, 2 right trisegmentectomies and 4 non-anatomical resections of 1 to 3 segments were performed. Postoperative complications developed in 25% with no operative mortality. Preoperative selective hepatic artery embolization helped to decrease the operative hemorrhage in 13 (mean blood loss- 1146 ml). In two cases severe bleeding required use of Cell-saver and massive donor blood transfusion. Our results suggest use of preoperative selective hepatic artery embolization and Cell-saver as an adjunct to the liver resection for these vascular tumors. PMID- 1911480 TI - Instrumental (operative) vaginal deliveries: vacuum extraction compared with forceps delivery at Ilorin University Teaching Hospital, Nigeria. AB - In a four-year period (1984 to 1987) a total of 141 Nigerian women who had instrumental vaginal deliveries at term in the Obstetric unit of University of Ilorin Teaching Hospital, Ilorin, were studied. Out of this number 79 had forceps delivery while 62 had vacuum extraction. The forceps delivery rate had fluctuated between 0.11% and 0.46% while the vacuum extraction rate had steadily increased from 0.08% to 0.39% (Table 1) in our unit over the 4-year period. With the exception of fetal distress, there were no significant differences found in the indications for forceps delivery and vacuum extraction. The preapplication station, position and cervical dilatation differ in both groups (Table 4). There was less maternal trauma in vacuum extraction than forceps (Table 5). The vacuum extraction was more associated with cephalhaematoma and neonatal jaundice but less with neonatal mortality compared with forceps (Table 7). Vacuum extraction had gradually assumed more prominence as an alternative to midforceps delivery in our unit in the study period. There was no maternal mortality in the two groups. PMID- 1911481 TI - Pitted red cell counts in Nigerian children with sickle cell anaemia: correlation with age and splenic size. AB - Pit counts, using direct interference phase-contrast microscopy (Normansky Optics) were carried out on 32 HbSS patients, aged 3-17 years. The influence of age and splenic size on the counts was also investigated. Nine (9) HbAS and HbAA age and sex-matched, healthy individuals served as controls. The mean +/- SD counts in the 3 groups were 11.1 +/- 9.1%, 1.7 +/- 1.4% and 1.8 +/- 1.7% respectively. The older SS patients tended to have higher values, but the linear correlation with age was not impressive (r = 0.28). Seventeen (53.1%) of the patients had counts in excess of 10%, while 8 (25%) had less than 3.5%. Five patients who had gross splenomegaly had a mean count of 4.3 +/- 1.9%, which was significantly lower than the figure of 12.3 +/- 7.9% for the patients without splenomeglay (p less than 0.001), thus demonstrating retained reticuloendothelial function in such patients. PMID- 1911482 TI - Some observations of peak expiratory flow in normal school children in northern Nigeria. AB - Peak expiratory flow rate and anthropometric measurements were made on 248 healthy secondary school children in Northern Nigeria. The male children have significantly higher values (P less than 0.01) of peak expiratory flow rate in comparison to female children. The peak flow rate measurements both in male and female children show positive correlation with height and weight and body surface area. It was observed that results obtained in the present study were significantly (P less than 0.001) lower than the predicted values derived from the formulae based on age and height of American children. PMID- 1911483 TI - Skin closure of laparotomy wounds: absorbable subcuticular sutures vs. non absorbable interrupted sutures. AB - In a five year period (1984-1988) in the department of obstetrics and gynaecology of the University of Ilorin Teaching Hospital, Ilorin, 304 laparotomy patients whose skin incisions were closed with the traditional method of interrupted non absorbable sutures or with absorbable subcuticular sutures were analysed. Out of these 304 patients, 164 had non-absorbable skin sutures while 140 had absorbable subcuticular sutures. The results of the two methods of skin closure were compared immediately on discharge, at 6 weeks and at 6 months after the operation. The appearance of the wounds and scar were better in the absorbable subcuticular group than in the non-absorbable interrupted group. The differences between the two groups were statistically significant in the cross-scar formation, Keloid/hypertrophic scar formation, period of hospitalisation and the acceptance rate. Subcuticular skin closure had the advantages of short stay in hospital, non stitch removal, better scar formation and being more acceptable to patients. There was no significant difference in the age between the two groups. All the patients were Africans. PMID- 1911484 TI - Problems in the management of aspirated foreign bodies. AB - Observations on nineteen cases of foreign bodies in the air passages have been presented. These mostly got lodged in the right bronchus (42.1%) and larynx (36.8%) while the commonest presenting complaint was respiratory distress. As many as 57.9 percent of our cases were aged two years or less. Large foreign bodies (above 20mm. size) were held up in the oropharynx; irregular and pointed medium sized objects (8-15mm) got stuck in the larynx while small, smooth or linear ones descended to the right bronchus. Absence of positive history, inconsistent clinical features and radiolucency of objects caused difficulty in diagnosis. Slow induction and laryngeal or bronchial spasm during anaesthesia, and fragmentation or impaction of the foreign body posed problems during endoscopic removal. Subglottic, tracheal or laryngeal inlet mucosal oedema were observed after removal of foreign body in six cases. A plea has been made to have a high degree of suspicion of foreign bodies in every child with respiratory symptoms of sudden onset. Endoscopy at the earliest has been recommended for prompt diagnosis and treatment. PMID- 1911485 TI - Serum copper, zinc and magnesium in maternal and cord blood at delivery. AB - Serum concentrations of copper, zinc and magnesium were determined in maternal and cord blood at delivery in term pregnancies among healthy Nigeria women. Maternal serum copper concentration was significantly higher than cord serum concentration. There were no significant differences in maternal and cord serum levels of zinc and magnesium. PMID- 1911486 TI - The effects of chloroquine on pulmonary saccular growth near term. AB - The Antimalaria drug, chloroquine is an amphiphilic cationic compound and might therefore be suspected to interfere with foetal lung maturity as previously observed with other amphilphilic cationic drugs. Single doses of chloroquine phosphate (40mg/kg b. wt) was administered to pregnant rats on days 20 and 21 of gestation (term = 22 days). Morphometric analysis revealed a decrease in volume density (Vv) of parenchyma, saccular space and average saccular volume. Concurrent administration of single doses hydrocortisone on day 21 increased the Vv of the Parenchyma saccules and average saccular volume. This result suggests that the retardation of foetal lung maturity induced by chloroquine could be reversed by a concurrent administration of hydrocortisone. Questions concerning the mechanism by which these effects are produced must remain open. PMID- 1911487 TI - Cholera and Vibrio parahaemolyticus diarrhoea endemicity in Calabar, Nigeria. AB - The microbiological and morbidity profiles of acute diarrhoeal episodes were studied in 881 patients seen at the Out-Patients Department of the University of Calabar Teaching Hospital (UCTH), Calabar, between January and December, 1988. Of a total of 108 (12.3%) culturally confirmed bacterial diarrhoeas, 47 (43.5%) were due to Escherichia coli, 33 (30.6%) to vibrios (Vibrio cholerae-01; classical and E1 Tor biotypes and V. parahaemolyticus), while shigella spp. and salmonella. spp. accounted for 29 (17.7%) and 9 (8.3%) episodes respectively. Twenty (64.5%) of the patients with vibrio diarrhoeas were children less than or equal to 10 years. The only case of diarrhoea-associated death observed, involved an 8-month old infant with kwashiorkor and V. parahaemolyticus infection. Bimodal peaks of cholera episodes occurred during the dry season and appeared to coincide with acute water shortage periods in the municipality. The significance of some prevailing ecological factors in stabilizing a focus of cholera and halophilic vibrio diarrhoea endemicity in this region is discussed. PMID- 1911488 TI - A study of serum antibody levels against Entamoeba histolytica in patients with different amoebic zymodemes. AB - The present study has looked into relative agreement between Clinical diagnosis, Indirect fluorescent Antibody Test and Iso-enzyme grouping in 35 patients with E histolytica infection. Thirty Caucasians, who had never travelled to Tropical Countries were chosen as negative control subjects. There was no remarkable difference in the mean amoebic antibody levels observed with the control subjects and patients harbouring amoebic zymodeme I or III or IV. Whereas, comparative analysis revealed a significant difference (P less than 0.01) between the mean reciprocal antibody titres observed with patients harbouring Isoenzyme group II amoebae and control subjects. The hypothesis that invasive amoebiasis and infection with E. histolytica zymodeme II were positively related was supported IFAT was found more sensitive than isoenzyme grouping in the detection of invasive amoebiasis, but the latter method appeared more reliable in differentiating dysenteric from asymptomatic intestinal amoebiasis. PMID- 1911489 TI - Motorcycle accidents in Nigeria. A new group at risk. AB - Multiple injuries often characterise motorcycle accidents. Head injury which is particularly common is a major cause of mortality, hence the enforcement of the law compelling all riders to wear helmets in most countries. The law collapsed in Nigeria about a decade ago. With the motorcycle becoming an important part of public transportation, infants, children and other age groups not usually associated with motorcycle accidents have become involved in the risk. A case of four month old baby with head trauma is presented to illustrate the point. The collapse of the law on helmets should be considered a temporary set back, and a new look taken at the challenges of motorcycle accidents. PMID- 1911490 TI - Cloacal extrophy. AB - Extrophic lesions of the ventral abdominal wall are represented by a range of anomalies of which the most severe is cloacal extrophy. By 1986, only 190 cases were reported in the world literature and it is estimated that only 15 cases are seen in the United States of America per year. In Nigeria today, with improvement in antenatal and perinatal services, children who one or two decades ago would have been stillborns or products of miscarriages are now born alive. This paper reports a case of cloacal extrophy in a Nigerian neonate and reviews the current management of the condition. PMID- 1911491 TI - Tuberculosis of the tonsil revisited. AB - With the advent of effective antituberculous therapy and pasteurisation of cow's milk, there has been considerable reduction in the worldwide prevalence of tuberculosis. Although tuberculosis of the tonsil is now an uncommon finding, tonsillar granulomata are occasionally seen by histopathologists and rarely, some contain tuberculous organisms. One such case has prompted us to examine the tonsils of seventeen cases of open pulmonary tuberculosis complaining of sore throat, dysphagia or other pharyngeal symptoms. No granulomata were demonstrated in fourteen who yielded representative tonsillar tissue, underlining the rarity of association between secondary pulmonary tuberculosis and tonsillar involvement. PMID- 1911493 TI - Tourniquet hypertension and its prevention: a review. PMID- 1911492 TI - Fracture of the hyoid bone with laceration of the pharynx. AB - A case of fracture of hyoid bone associated with laceration of the pharynx and producing severe dysphagia is presented. The mechanism of the injury, the diagnosis and treatment policy of this rare condition are highlighted to alert clinicians of the importance of the injury. PMID- 1911494 TI - Response to maintenance of tourniquet inflation in a primate model. AB - Several theories have been proposed, but the etiology and pathway of neural transmission for the sensation of tourniquet pain remain unknown. This study was designed to observe the circulatory response and to measure the stress response markers associated with maintenance of tourniquet inflation in an anesthetized primate model. Eight African Green monkeys (Cercopithecus aethiops) were anesthetized, and heart rate (HR) and systolic and diastolic blood pressure (SBP and DBP) were measured every five minutes. In each animal, a control trial without tourniquet inflation was compared to an experimental trial with tourniquet inflation on the left lower extremity to 300 mmHg for a period of 90 minutes. After maintenance of tourniquet inflation for a period of 30-45 minutes, each animal demonstrated a gradual, progressive increase in HR, SBP and DBP as compared to preinflation baseline values (p less than 0.05). An increase in serum cortisol and plasma norepinephrine was demonstrated to correlate with the circulatory response in this model. The results of this study suggest that the circulatory response to maintenance of tourniquet inflation in this animal model may be mediated by a neurohumoral response to tourniquet pain and that an animal model may be appropriate for further studies into the etiology and neural pathways associated with the sensation of tourniquet pain. PMID- 1911495 TI - The effect of fentanyl, meperidine and diamorphine on nerve conduction in vitro. AB - The effect of fentanyl, meperidine and diamorphine on A- and C-fiber conduction in an in vitro rabbit vagus nerve preparation was examined. The nerves were maintained at 37 degrees C with an oxygenated electrolyte solution. The effect of the commercial preparation of fentanyl (Sublimaze) and isotonic solutions of fentanyl, meperidine and diamorphine were observed. Sublimaze had a neurotoxic effect related to its hypotonicity. In isotonic solutions, fentanyl and meperidine, but not diamorphine, blocked nerve conduction and both showed marked frequency-dependent blocking actions in C-fibers. Naloxone (Narcan) did not prevent the effect of fentanyl. Both fentanyl and meperidine potentiated the block produced by a low concentration of bupivacaine (0.005 mM, 0.00016%), the effect of meperidine being seen at clinically relevant concentrations. Fentanyl was slightly more potent than meperidine in its effect on nerve conduction, but its greater opioid potency would not allow its use as a local anesthetic. The local anesthetic effect of meperidine may be more useful clinically. PMID- 1911496 TI - Technical complications during long-term subarachnoid or epidural administration of morphine in terminally ill cancer patients: a review of 140 cases. AB - The type and incidence of technical complications (e.g., obstruction and dislocation of the catheter and infection) in long-term (ten to 366 days) spinal morphine administration in terminally ill cancer patients by means of an epidural or subarachnoid catheter are presented. Total treatment time was 8650 days, of which patients spent 6175 at home. Portable external mini infusion pumps were used with satisfactory results in 15 patients of the epidural group (n = 110) and in all patients receiving subarachnoid morphine (n = 30). In the other 95 patients of the epidural group, intermittent bolus injections were used. During the first 20 days of treatment, a significant difference (chi-square test, p = 0.02) in the incidence of complications was observed between the epidural group (8%) and the subarachnoid group (25%). During the remainder of the treatment period the complication rate rose to 55% in patients receiving epidural morphine and declined to 5% in the subarachnoid group, a significant difference (chi square test, p = 0.001). The most frequent complication in the epidural group was obstruction and dislocation of the catheter, probably due to the development of epidural fibrosis. This problem became apparent in 50% of patients during the treatment period from Day 20 to 366. In patients receiving subarachnoid morphine, the prevalent complication was CSF leakage, which was observed only during the first two weeks of treatment. The subarachnoid route is preferred for patients expected to live longer than one month. For patients with a shorter life expectancy, epidural administration can yield acceptable results. PMID- 1911497 TI - Combination of epidural morphine and fentanyl for postoperative analgesia. AB - The rapid onset of epidural fentanyl could be used to cover the latency period of epidural morphine, thus potentiating analgesia during anesthesia regression after short-acting local anesthetics and possibly extending morphine analgesia for longer duration. The object of this study is to determine whether there are clinical advantages or disadvantages of combining epidural morphine and epidural fentanyl for postoperative analgesia. Patients scheduled for gynecologic procedures were assigned to two groups (n = 54 for each): Group 1 receiving 4 mg epidural morphine, and Group 2 receiving 4 mg epidural morphine and 100 micrograms fentanyl 30 minutes before the estimated completion of the surgery using lidocaine epidural anesthesia. Comparisons were made with regard to: (1) times before the first supplemental analgesic for incisional pain, (2) numbers of supplemental analgesic during the first 48 hours postoperatively, and (3) adverse effects. The two groups were comparable. The number of patients requiring supplemental analgesics between the fourth and 17th hours was significantly greater in Group 1 (n = 10, compared to n = 0 for Group 2; p less than 0.05). The mean time before the first supplemental analgesic was significantly longer in Group 2 (p less than 0.05). The number of supplemental analgesics during the first 48 hours was significantly less in Group 2 (p less than 0.01). No significant difference was found regarding adverse side effects. The results obtained confirm the potential desirability of combining epidural morphine and epidural fentanyl for postoperative analgesia. PMID- 1911498 TI - Intravenous lidocaine does not cause shivering-like tremor or alter thermoregulation. AB - We tested the hypotheses that systemic absorption of epidural lidocaine: (1) contributes to the shivering-like tremor seen during epidural anesthesia by causing central nervous system disinhibition of spinal reflexes, or (2) activates or alters thermoregulatory mechanisms. In a double-blind, placebo, cross-over study, nine healthy volunteers were given intravenous lidocaine (or saline) to approximate the plasma levels of lidocaine achieved during epidural anesthesia for major abdominal surgery. Five volunteers were studied in a warm room (to test for nonthermoregulatory tremor), and four volunteers were studied in a cold room (to test the effects of lidocaine on normal thermoregulation). Central temperatures, peripheral vasoconstriction, tremor and clonus were unaffected by intravenous lidocaine. We conclude that the systemic absorption of epidural lidocaine does not contribute to tremor or shivering by these mechanisms. PMID- 1911499 TI - A rodent model for studying four well defined toxic endpoints during bupivacaine infusion. AB - An animal model with four well defined endpoints for studying the cardiotoxicity and neurotoxicity of bupivacaine is described. Five male Wistar rats (264-324 g) were anesthetized, tracheostomized and ventilated, and ECG and EEG leads were placed. Femoral arteries and veins were then cannulated. Twenty minutes before bupivacaine infusion, 0.1 mg/kg pancuronium was given intravenously, and anesthesia was adjusted to halothane 0.5%, 30% O2 and 70% N2O. Bupivacaine infusion was then begun at 2 mg/kg/minute. Bupivacaine doses producing the following endpoints were then determined: (1) first ventricular arrhythmia (ARR), (2) seizures (SZ), (3) isoelectric EEG (ISO EEG), and (4) asystole (ASYS). The doses of bupivacaine (in mg/kg +/- SD) precipitating AAR, SZ, ISO EEG and ASYS were 4.22 +/- 1.87, 7.08 +/- 1.55, 11.05 +/- 5.15 and 20.4 +/- 6.49 mg/kg, respectively. These endpoints were present and readily determined in all animals. The doses of bupivacaine producing ARR and SZ were not significantly different (p greater than 0.05). The doses producing SZ, ISO EEG and ASYS were significantly different from each other (p greater than 0.05, ANOVA and the Duncan test). These results indicate that it is possible to study, in the anesthetized and paralyzed rat that is intensely monitored, many of the variables associated with local anesthetic toxicity currently of clinical interest. The use of a constant local anesthetic infusion allows ready observation of the progression of toxic signs. PMID- 1911500 TI - Comparison of onset time between 0.5% bupivacaine and 3% 2-chloroprocaine with and without 75 micrograms fentanyl. AB - We tested the hypothesis that the addition of 75 micrograms fentanyl to 0.5% bupivacaine would reduce the onset time of surgical anesthesia for cesarean delivery to equal the onset time of 3% 2-chloroprocaine and would have no effect when added to 3% 2-chloroprocaine. Fentanyl was found to reduce the onset time of bupivacaine to equal the onset time of 2-chloroprocaine and have no effect when added to 2-chloroprocaine. PMID- 1911501 TI - A comparison of postcesarean epidural morphine analgesia by single injection and by continuous infusion. AB - To assess the relative efficacy and incidence of side effects of a single injection versus a continuous infusion of epidural morphine sulfate (MS) in the postcesarean population, the authors report a prospective, randomized, double blind study. Thirty-one patients received either a 5-mg MS bolus and subsequent saline infusion (n = 13) or a 2.6-mg MS bolus and subsequent MS infusion at 0.1 mg/hour (n = 18), such that after 24 hours both groups had received a total MS dose of 5 mg. No statistically significant differences were found between the two groups in overall satisfaction with analgesia, verbal pain scores, level of activity, need for supplemental opioids, or incidence of sedation during the 24 hour study period. The authors conclude that in this population, continuous epidural morphine infusion offers no obvious advantage over single morphine bolus therapy. However, the theoretical merits of continuous opioid infusion therapy are discussed. PMID- 1911502 TI - Identification of epidural space by drip method. AB - In 100 pregnant women, identification of the epidural space was performed by a modified drip method. A saline infusion was prepared, leaving the distal 40 cm of infusion tubing full of air, and then attached to the hub of a Tuohy needle. Accurate identification of the epidural space was accomplished in less than one minute in 95% of cases. There were no unintentional dural punctures. This technique has advantages over the hanging drop and the manual loss of resistance techniques. PMID- 1911503 TI - Lumbar epidural anesthesia initiated in the knee-chest position. AB - The knee-chest position may become necessary in labor to mitigate fetal heart rate decelerations. This position may also prove advantageous for initiation of lumbar epidural anesthesia. This case report demonstrates a clinical situation in which lumbar epidural anesthesia was initiated in the knee-chest position. A description of the technique is included. PMID- 1911504 TI - Horner's syndrome after epidural block in early pregnancy. AB - Horner's syndrome after epidural block in a first-trimester parturient has not previously been reported. The authors describe a case of unilateral Horner's syndrome after single-dose epidural block in a 12-week pregnant female. PMID- 1911505 TI - Does propofol relieve epidural or subarachnoid morphine-induced pruritus? PMID- 1911506 TI - Solidstate refractive lasers evolve slowly. PMID- 1911507 TI - Phakic intraocular lenses for the correction of myopia--where do we go from here? PMID- 1911508 TI - Damage to the corneal endothelium from anterior chamber intraocular lenses in phakic myopic eyes. AB - The use of minus power anterior chamber intraocular lenses to correct myopia in phakic eyes has been demonstrated previously to produce a more accurate and predictable correction than corneal refractive surgery techniques. We have examined 15 such eyes by specular microscopy and 10 such eyes by Scheimpflug slit lamp micrography. One year after surgery, in 5 (36.3%) eyes, there was a decrease of more than 20% in the central endothelial density. Paracentral endothelial damage was present in 13 eyes (86.6%). On the specular micrograph, this damage appeared as an overall decrease in the number of the cells, abnormal cell shape with marked pleomorphism, dark zones, and acellular zones that corresponded to endothelial defects. The slit-lamp anterior segment measurements showed a distance between the edges of the IOL optic and the endothelium which ranged from 0.71 to 1.50 mm. We discuss the criteria for intraocular lens removal. PMID- 1911509 TI - Damage to the corneal endothelium by minus power anterior chamber intraocular lenses. AB - We present 16 phakic myopic eyes (from -10.00 to -25.00 diopters) corrected by minus power intraocular lenses implanted in the anterior chamber whose corneal endothelium was observed by specular microscopy during a postoperative period from 6 to 18 months. Significant morphologic endothelial changes were noted in three eyes along the border of the lens optic. Around dark zones, which appeared acellular, endothelial cells were enlarged, deformed, and separated. These findings may be produced by intermittent contact between the endothelium and lens. Corneal indentation during specular microscopy occasionally caused a curvilinear reflection which corresponded to the optic border. In three eyes, dark areas without cellular abnormality were observed near the curved edge of the lens. These findings probably resulted from the disturbance of the specular reflection on part of the endothelium due to this edge. PMID- 1911510 TI - Correction of myopia by implantation of a concave Worst-iris claw lens into phakic eyes. AB - The Worst-Fechner Biconcave Lens for the correction of myopia in phakic eyes is fixated to the anterior iris. Of the 125 eyes implanted between November 1986 and November 1990, 109 eyes ("core group") had a follow-up period of at least 12 months (mean, 25.0; range, 13 to 51). Sixty-eight of these eyes were reexamined at Giessen University Eye Clinic by an independent investigator using a laser flare cell meter; 23 of the eyes also were examined by iris fluorescence angiography. Seventy-five of the 109 eyes (68.8%) were corrected within 1.00 diopters of the desired refraction, and only 10 eyes (9.2%) deviated more than 2.00 D from the calculated correction. The anatomical results were characterized by good fixation, absence of glaucoma, inflammation, and leak from iris vessels. However, the corneal endothelium was damaged in five eyes by surgical trauma, three resulting in corneal edema. In addition, in five eyes the endothelial density decreased during the follow-up period despite an uncomplicated operation, resulting in corneal edema in one eye. These eyes may have had anterior chambers that were too shallow. PMID- 1911511 TI - A study of the optical micrometer, the coin gauge, and the diamond knife micrometer in diamond knife calibration. AB - Reproducible results in refractive keratectomy are greatly influenced by an accurate setting of the diamond knife blade length. In this study, we evaluated the accuracy and reproducibility of three existing techniques of blade calibration: the KOI coin gauge, the KOI diamond knife handle micrometer, and the Magnum optical micrometer. Serial blade length measurements of three similarly designed KOI diamond knives were made using each of the above calibration methods. The three knife handle micrometers had the largest measurement error (3.55%, 2.83%, 1.82%), and therefore the sole reliance of the handle micrometer for blade calibration was not recommended. The measurements made by the coin gauge on the three knives had measurement errors of 1.03%, 1.64%, and 1.46%. The optical micrometer achieved an accuracy of 0.005 mm and an interobserver precision of 0.009 mm. We prefer using the optical micrometer because the potential for parallax error is eliminated; it has a lower risk of blade damage; it is easier to use; and it also allows detection of defects in the footplates, the diamond knife, and of the wobbling blade, which may contribute to calibration error. PMID- 1911512 TI - Intraocular pressure and the intrastromal corneal ring. AB - The intrastromal corneal ring is a refractive surgery device placed in the peripheral cornea at 2/3 depth, and it has the potential to correct both myopia and hyperopia. This study examined whether intraocular pressure (IOP) could be accurately measured with the ring in place and whether intraocular pressure was altered as a result of surgery. Fifteen eye bank eyes were attached to a manometric device to control pressure (10 to 40 mm Hg) which was measured over the range before and after placement of the ring with a pneumotonometer. A paired t-test showed no significant difference in pressure, pre- vs postoperative. To determine the effect of the ring on IOP in vivo, ring implantation was performed on 10 rabbit eyes and pressure measured before and after surgery. At 24 and 48 hours postoperatively, there was no significant change in IOP (3 +/- 2 mm Hg, P greater than .05, and 9 +/- 8 mm Hg, P greater than .20 respectively) and facility of outflow calculated from tonography showed no significant change. PMID- 1911513 TI - Safety of ophthalmic excimer lasers with an emphasis on compressed gases. PMID- 1911514 TI - Combined surgical and medical treatment of fungal abscess in a pseudophakic eye. PMID- 1911515 TI - Pseudophakic bullous keratopathy. PMID- 1911516 TI - Radial thermokeratoplasty for the correction of hyperopia. PMID- 1911517 TI - Continuous tear capsulotomy and phacoemulsification during penetrating keratoplasty. PMID- 1911518 TI - Fixation light for the determination of optical axis. PMID- 1911519 TI - Blepharochalasis. A review of 30 cases. AB - This paper presents the findings in a series of 30 patients with blepharochalasis, including the age of onset, sex, predisposing factors, symptoms and signs, frequency and duration of attacks, and length of the history. There were 16 bilateral and 14 unilateral cases. The condition can be divided into an active (early) and a quiescent (late) stage. The active stage is further subdivided into intumescent (hypertrophic) and atrophic forms. The sequelae included excess thin skin, fat herniation, lacrimal gland prolapse, ptosis, blepharophimosis, pseudoepicanthic fold, proptosis, conjunctival injection and cysts, entropion, and ectorpion. Surgery primarily involved blepharoplasty, ptosis correction, and lateral canthal reattachment alone or in combination. The pathology showed a variable picture of epithelial atrophy, vasculitis, and loss of elastic fibers, which did not greatly help to differentiate blepharochalasis from angioedema, lymphedema, dermatochalasis, tumors and infiltrations, and floppy lid syndromes. Blepharochalasis is probably a localized angioedema. The diagnosis depends on the clinical features of intermittent attacks of localized swelling affecting one or more eyelids associated with thinning of the skin giving either an intumescent (hypertrophic) or atrophic appearance in the active stage of the condition and progressing to atrophic changes in the quiescent (late) stage. PMID- 1911520 TI - Anatomic considerations in upper eyelid retraction. AB - A series of anatomically correct orbital drawings are created to examine the major integrating factors that determine upper eyelid position on the eye. The principal upper eyelid force planes can be identified as (1) the eyelid vertical retractor plane slightly divergent from the orbital axis, (2) the eyelid protractor plane nearly tangent to the orbital aperture, and (3) the upper eyelid tarsalligamentous plane swinging from within the horizontal orbital rims. These forces are governed by variation in orbital size and shape, globe size and position, and the length-tension characteristics of the eyelid retractors, protractors, and lamellae. Enhanced lateral upper eyelid retraction occurs in part because the eye in primary position looks away from the orbital axis and projects more lateral sclera. When the eye gazes laterally, coincident with the orbital axis, enhanced lateral upper eyelid retraction disappears. PMID- 1911521 TI - Management of epiphora in the presence of congenital punctal and canalicular atresia. AB - We treated ten eyes in six pediatric patients with epiphora and punctal and canalicular atresia in one or both lids. Attempted probing and irrigation had failed to improve the epiphora. Nine out of ten of the lacrimal systems had additional anomalies, such as cutaneous lacrimal fistulas (anlage ducts), small sacs, and nasolacrimal duct stenosis or obstruction. A surgical plan is described for the exploration and reconstruction of these markedly abnormal nasolacrimal drainage systems, including a new method of performing bicanalicular intubation. Four of the five eyes with at least part of one canaliculus present have had resolution of epiphora. PMID- 1911522 TI - Argon laser versus thermal cautery for punctal occlusion. An animal study. AB - A subset of the dry-eye patient group manifests their problem so severely that permanent punctal occlusion is required. The technique most often used today is thermal cautery. In this prospective study, an animal model was developed, and the effectiveness of the argon laser as a primary alternative therapy to thermal cautery was evaluated. Dogs were found to have a punctum similar in shape and location to humans; therefore, they were deemed to be a more appropriate animal model for punctal studies than cats. Both laser and thermal cautery are similarly effective in completely occluding puncta in animals. There was a trend toward greater stenosis with the laser in those puncta that were only partially occluded. In addition, laser punctal occlusion appeared to be less painful than thermal cautery. PMID- 1911523 TI - Nasal catheter use in dacryocystorhinostomy. AB - A modification of the standard dacryocystorhinostomy (DCR) techniques using a self-retaining nasolacrimal catheter to act as a stent to improve the success rate of nasal ostium patency is described. A series of 21 DCRs performed on 19 patients is presented that includes eight procedures on previously failed DCRs, nine procedures on primary idiopathic obstruction of the nasolacrimal duct, and four procedures where trauma was the etiology. This technique has had no failures except for two procedures that failed because the catheter was too short. This prospective study over 3 years using this technique has resulted in no other cases of closure of the nasal ostium. PMID- 1911524 TI - Bell's palsy in Moebius syndrome. AB - We report a case of unilateral transient and reversible facial paresis, which was superimposed on a congenital bifacial palsy in a young adult with Moebius syndrome. Our case illustrates the potential for two conditions, both affecting the facial nerve and both of unknown etiology, to be juxtaposed in a single individual. Worsening of facial palsy in the Moebius syndrome may not signify progressive disease. PMID- 1911525 TI - Histoacryl closure of eyelid skin grafts. AB - Histoacryl is virtually an ideal tissue glue. It has found application in corneal surgery, oculoplastic surgery, as well as many other surgical fields. A clinical series of 18 patients requiring eyelid skin grafts is presented. Each of the patients had skin grafts placed with a combination of sutures and Histoacryl. No complications were encountered. The postoperative course and results were identical to the authors' experience with skin grafts closed with suture alone. The advantages of Histoacryl skin closure are discussed. Other uses of Histoacryl in oculoplastic surgery are also reviewed. PMID- 1911526 TI - Long-term follow-up of severely injured eyes following globe rupture. AB - There is little information concerning the outcome of severely traumatized eyes, with little visual potential, which are not removed. We studied 50 eyes, which had suffered severe globe rupture, had visual acuities of no better than hand motion, and were not removed within 2 weeks of injury. Seventeen (34%) of the 50 eyes were later removed. Of the 17, nine had become painful. The other 33 eyes, which were not removed, remained comfortable over a mean follow-up of 66 months (12-161 months). Thirty (70%) of 43 eyes, which had follow-up of at least two months, became phthisical. There were no cases of sympathetic ophthalmia. These results suggest that the majority of severely-injured eyes become phthisical, but do not require removal for pain. PMID- 1911527 TI - Self-compression plates for orbital rim fractures. AB - The development and principles of self-compression plating, as well as a series of patients treated with this technique, are described. The use of such plates has specific advantages over other techniques for disorders encountered by the oculoplastic surgeon. The indications for plating were displaced trimalar fracture, displaced trimalar fracture with orbital rim fragment, and comminuted orbital rim fracture. Results were good; no complications have been observed to date. Comparison of compression plating to other methods for repair of orbital fractures is made. Self-compression plating with Vitallium plates is an effective modality for the treatment of a broad spectrum of patients with orbital rim fractures. PMID- 1911528 TI - Orbital angiolymphoid hyperplasia with eosinophilia. Presentation as chalazion. AB - Angiolymphoid hyperplasia with eosinophilia (ALHE) is an uncommon, benign slow growing lesion primarily found in the head and neck region, with onset between the third and fourth decades, and a female predominance in the nonOriental population. Kimura's disease, occurring primarily in young Oriental males, is a similar lesion with peripheral blood eosinophilia, regional lymphadenopathy, and occasional nephrotic syndrome. Orbital ALHE is rare, previously reported in only nine patients. Orbital ALHE is a solitary lesion, with an older age of onset, between the fourth and eighth decades, than ALHE elsewhere. There is a male predominance, in contradistinction to ALHE elsewhere in nonOrientals. Orbital ALHE demonstrates the same histology as other locations, with exuberant capillary proliferation and an inflammatory infiltrate of eosinophils, lymphocytes, plasma cells, and mast cells. The maturity of the lesion, not necessarily the duration, determines the presence of lymphoid follicles and germinal centers. A distinctive endothelial cell lines and even extends into the vascular lumens. Peripheral blood eosinophilia occasionally occurs, and a few cases have been reported in conjunction with asthma. Therapeutic regimens for ALHE include excision, carbon dioxide and argon laser, irradiation, steroids, electrodesiccation, and cytotoxic agents. Orbital lesions have been treated successfully with excision, or biopsy with debulking, or steroids. PMID- 1911529 TI - Use of Proplast II. PMID- 1911530 TI - Production of citrulline and ornithine by interferon-gamma treated macrophages. AB - Activated macrophages exert strong arginase (ASE) activity that converts L arginine into ornithine, the key precursor for putrescine and polyamine biosynthesis. Macrophages were previously also shown to generate nitric oxide that is derived from the guanido group of arginine by the oxidative deiminase (OAD) reaction. In view of the physiological importance of ornithine and putrescine, we now investigated whether interferon-gamma (IFN-gamma), a principal stimulator of the OAD activity, may lead to the accumulation of the deiminated derivative citrulline at the expense of ornithine production, or whether the carbon backbone could be reutilized for the production of arginine and ornithine. Our experiments show that murine peritoneal macrophages treated with IFN-gamma in combination with tumor necrosis factor (TNF) or bacterial lipopolysaccharide (LPS) generate substantial amounts of citrulline as identified by amino acid analyzer and by thin-layer chromatography. Also, labeled citrulline is generated from [14C]L-arginine but not from [14C]L-ornithine. This suggests that macrophages have little or no capacity to convert ornithine into arginine. In the absence of IFN-gamma, TNF and LPS stimulate the conversion of arginine into ornithine but not citrulline. However, when TNF or LPS stimulated macrophages are simultaneously treated with IFN-gamma, ornithine production is relatively inhibited by the strong OAD reaction that competes with the ASE reaction for its substrate L-arginine. IFN-gamma thus down-regulates the availability of ornithine and putrescine. The lipid A precursor IA also induces, in conjunction with IFN gamma, the production of citrulline but fails to stimulate the generation of ornithine. PMID- 1911531 TI - Interplay between IL-2 and IL-4 in human thymocyte differentiation: antagonism or agonism. AB - The effect of recombinant interleukin 2 (IL-2) and IL-4, as well as a combination of both lymphokines on human post-natal thymocytes at different maturation stages, was analyzed by culturing highly purified pro-T cells, pre-T cells, double-negative and double-positive thymocyte subsets in the presence of IL-2 and/or IL-4. Both IL-2 and IL-4 responsiveness are developmentally regulated in human thymocytes, since IL-2 and IL-4 responses decline with increasing thymocyte differentiation, double-positive T cells displaying far less proliferation than immature thymocytes. IL-2 and IL-4 may influence pro-T cell growth in both an antagonistic and additive fashion. At low doses, IL-4 inhibits IL-2-supported growth of pro-T cells, whereas, at higher concentrations, this inhibitory effect is masked by the ability of IL-4 to stimulate pro-T cell proliferation. In contrast to peripheral lymphocytes, IL-4 does not down-regulate the expression of the IL-2 receptor light chain on thymocytes. In pro-T cell cultures, IL-2 and IL 4 favour the differentiation of distinct cell populations, namely lymphocytes displaying preferentially a TCR alpha/beta+ and CD4+CD8- phenotype versus predominantly TCR gamma/delta+ and CD4-CD8+ cells, respectively. The effect of IL 2 dominates over that of IL-4, since the composition of cultures set up in the presence of IL-2 plus IL-4 resembles that of cells cultured with IL-2 alone. In synthesis, IL-2 and IL-4 exhibit reciprocal inter-relations in human thymocyte cultures, thus supporting the notion that these lymphokines are implicated in the complex regulation of a local cytokine network. PMID- 1911532 TI - Xid immunodeficiency imparts increased parasite clearance and resistance to pathology in experimental Chagas' disease. AB - Infection of several mouse strains with Trypanosoma cruzi stimulates high levels of T and B lymphocyte activities which persist during the chronic phase and is followed by specific immunosuppression and severe autoimmune pathology. Infected BALB.Xid mice carrying an X-linked mutation and lacking CD5 B cells, display poor B cell responses to T. cruzi infection, accompanied by low levels of specific and non-specific immunoglobulins in the serum. However, these animals control parasitemia, do not show the wasting observed in BALB/c mice, and develop almost no pathology early in the chronic phase. The infection of (BALB.Xid female x BALB/c male) F1 animals shows that immunodefective males behave like Xid animals in contrast to females which respond as normal BALB/c mice. These results indicate that the Xid locus controls lymphocyte responses, parasite clearance and pathology in experimental Chagas' disease. PMID- 1911533 TI - Susceptibility to infection with Mycobacterium avium is paradoxically correlated with increased synthesis of specific anti-bacterial antibodies. AB - A comparison was made between the levels of splenic and intestinal (Peyer's patches and thin intestinal epithelium) Ig production of C57BL/6 germ free and conventional C57BL/6, BALB/c, DBA/2 and C3H/He mice and the susceptibility to Mycobacterium avium infection, evaluated by the number of bacterial colony forming units (CFU) found in the liver and in the spleen of the animals. Mice received an i.p. injection of either 5 x 10(6), 10(7) or 10(8) bacteria, or were given the larger inoculum intragastrically. Alternatively, mice were treated with an i.p. injection of M. avium bacterial sonicates. A marked increase of splenic IgA production, quantitatively associated with the size of the inoculum and thus with the degree of infection, was observed in susceptible compared to relatively resistant mice. This increase was observed at an earlier time following infection with the larger rather than with the smaller inocula. Consistent significant increases in splenic production of IgG isotypes were only observed in the susceptible mice after infection with the intermediate and larger inocula whereas a comparative increase of IgM was only clearly observed after infection with the larger inoculum. Intestinal Ig production remained unchanged, however, in both susceptible and relatively resistant mice after i.p. infection. Also, all mice were resistant to M. avium infection by the intragastric route and with this site of entry splenic and intestinal Ig production remained unchanged. Susceptibility to M. avium infection was also quantitatively associated with increased levels of circulating specific anti-bacterial antibodies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1911534 TI - Measurement of recombinase activity in a set of related Abelson murine leukemic virus pre-B cell lines: DJ/DJ lines have more recombinase activity than do VDJ/VDJ lines. AB - The VDJ recombination potential of a number of Abelson murine leukemic virus transformed fetal liver cell lines derived from (C57BL/6 x BALB/c) F1 mice was measured. The specific developmental stage of each line was determined using Southern blot analysis to ascertain their rearrangement status at the immunoglobulin heavy chain locus (DJ/DJ, VDJ/DJ or VDJ/VDJ). It was observed that DNA from DJ/DJ lines gave many more 'subhaploid' bands hybridizing with JH than did DNA from VDJ/VDJ lines. While the lack of appropriate substrate (VDJ/VDJ lines have exhausted the normal IgH substrate) contributes to the decrease in 'subhaploid bands', this result indicates that the rate of ongoing immunoglobulin heavy chain gene rearrangement was higher in the DJ/DJ lines. However, when the lines were examined using the assay developed by Hesse et al. (4) to measure VDJ recombinase activity, it was found that although all lines had recombinase activity, the DJ/DJ lines had four times more VDJ recombinase activity than did the VDJ/VDJ lines. PMID- 1911535 TI - Analysis of the immunoactivator sites of parotid protein isolated from bovine parotid glands. AB - Parotid protein (parotin) was isolated from bovine parotid glands. To analyze the active site of parotid protein, the parotid subunit (PS) was digested by trypsin and then fractionated on a Sephadex G-25 column. Fraction A induced mainly polyclonal antibody responses and interleukin 1 (IL-1)-like activities. FrAA-1, consisting of 58 amino acids (LYILYFFQSDNEDKEKVVRQEEGEE RITALLMNGSALKQEEWWEKEDTDDTAIVLLK) was isolated from fraction A by chromatography on QAE-Sephadex A-25 columns. FrAA-1 was found to possess IL-1-like activity. There was only 29% homology between FrAA-1 and four IL-1 molecules. When 10- and 20-residue peptides based on the amino acid sequence of FrAA-1 were synthesized, P-10.2 (TDDTAIVLLK) alone exerted an IL-1-like effect on C3H/HeJ thymocytes, whereas P-20.1 (SDNEDKEKVVRQEEGEERIT) alone elicted polyclonal IgM and IgG antibody production in human lymphocytes. These results suggest that the active sites for polyclonal B-cell activator (PBA) and IL-1-like activity have different locations in FrAA-1. PMID- 1911536 TI - Expression and function of Qa-2 major histocompatibility complex class I molecules in transgenic mice. AB - Qa-2 molecules are weak transplantation antigens encoded by class I genes of the major histocompatibility complex. When expressed in transgenic CBA mice, Qa-2 molecules provoke rapid rejection of skin grafts and strong, Qa-2 specific, cytotoxic T-cell responses. Efficient rejection of skin grafts from Qa-2 transgenic mice takes place when Qa-2 molecules are attached to the cell membrane with a glycophosphatidyl anchor or by a transmembrane protein domain, except that rejection times are slightly longer in the former case. These results demonstrate that Qa-2 molecules can behave as major transplantation antigens, as do closely related H-2 molecules. Failure of Qa-2 molecules to provoke strong T-cell responses in non-transgenic mice is probably due to the very low level of expression of Qa-2 molecules in skin keratinocytes from such mice since these cells express increased levels of Qa-2 molecules in all Qa-2 transgenic mice. PMID- 1911537 TI - HLA-DR4Dw4-restricted T cell recognition of self antigen(s) in the rheumatoid synovial compartment. AB - The pathogenesis of joint destruction in rheumatoid arthritis remains ill defined, although it is thought to be the result of tissue damage mediated by T cells. This prompted us to isolate and characterize in vivo activated T cells from rheumatoid arthritis synovial fluid in an attempt to determine their specificity. Heterogeneous synovial fluid cells, containing both adherent and non adherent cell types, were recovered from joint aspirates and cultured in the presence of IL-2. After 2 weeks, the non-adherent cells were phenotyped as CD3 positive and TCR alpha beta-positive T cells. Polyclonal T cell lines were derived from four rheumatoid arthritis patients; of these, two proliferated, in a dose-dependent manner to only autologous synovial fluid in the presence of autologous or DR4Dw4 histocompatible antigen presenting cells. T cell proliferation to the synovial fluid could be inhibited by monomorphic anti-HLA-DR monoclonal antibody, but not by anti-DQ or anti-class I antibodies. T cell clones were established by limiting dilution of a synovial T cell line in the presence of autologous synovial fluid and DR4Dw4 histocompatible accessory cells. Examination of the antigen specificity of these T cell clones demonstrated that they were reactive with a component of synovial fluid. The results of these experiments suggest the presence of an MHC class II-restricted antigen in the rheumatoid arthritis synovial compartment that induces proliferation of in vivo activated T cells. PMID- 1911538 TI - Characterization of the enhancer region for germline transcription of the gamma 3 constant region gene of human immunoglobulin. AB - A constant region gene (C) of the immunoglobulin heavy chain can be transcribed as germline transcripts from a promoter located upstream of a switch region. We have studied the structure and function of the human C gamma 3 promoter region. When the human IgM-producing cell line SSK41 is stimulated with interleukin 4 (IL 4) in the presence of phorbol myristate acetate (PMA) or Staphylococcus aureus Cowan I, expression of germline C gamma 3 transcripts was specifically augmented within 4 h. Upstream DNA fragments flanking the I gamma 3 exon were fused with a reporter gene and tested for IL-4-induced promoter/enhancer activity by transfection of SSK41 cells. The DNA fragment between 450 and 250 bp upstream of the transcription initiation site of the C gamma 3 gene was shown to be required for transcriptional up-regulation by PMA and IL-4. The upstream 514 bp fragment of the I gamma 3 flanking region was shown to contain an enhancer activity in response to PMA and IL-4. PMID- 1911539 TI - Molecular characterization of the beta chain of the murine interleukin 5 receptor. AB - Interleukin 5 (IL-5) is a multifunctional cytokine that regulates the proliferation and differentiation of hematopoietic cells including B cells and eosinophils. The murine IL-5 acts on target cells via an IL-5 specific high affinity receptor (Kd approximately 150 pM) that has been proposed to be composed of at least two membrane polypeptide chains. The p60 component recognized by anti murine IL-5 receptor mAbs H7 and T21 binds IL-5 with low affinity (Kd approximately 10 nM). The other component is p130, detectable by following cross linking experiments with IL-5. Using H7, T21, and R52.120 mAbs specific to murine IL-5 receptor, we characterized the molecular nature of the p130 of the high affinity receptor for murine IL-5. R52.120 mAb did not recognize the IL-5 binding recombinant p60 expressed on COS7 cells, but reacted with p130/140 on IL-5 dependent cell lines. R52.120 mAb showed partial inhibition of the IL-5-induced proliferation of the IL-5-dependent early B cell line Y16 at high IL-5 concentrations. Addition of R52.120 mAb together with H7 or T21 mAb caused more striking inhibition of the IL-5-dependent proliferation than that caused by either of them alone. R52.120 mAb down-regulated the number and dissociation constant of IL-5 binding sites with high affinity without affecting the levels of these with low-affinity. It also preferentially inhibited the formation of the cross-linked complex of p130 with radiolabeled IL-5. These results indicate that p130/p140, recognized by R52.120 mAb, is indispensable, together with p60, for the formation of high affinity IL-5 receptor. We propose to designate p60 and p130/p140 as the alpha and beta chain of IL-5 receptor, respectively. PMID- 1911540 TI - Characterization of an active, non-myristylated, cytoplasmic form of the lymphoid protein tyrosine kinase pp56lck. AB - pp56lck is a member of the src family of tyrosine kinases mainly expressed in T lymphocytes. Src tyrosine kinases have been implicated in the control of cell growth and differentiation in different cell types, but the mechanism of regulation of these enzymes is poorly understood. In order to characterize the distinct species of pp56lck, we have produced high yields of enzymatically active wild type pp56lck using the eukaryotic baculovirus expression system in Spodoptera frugiperda insect cells (Sf9). We find that the various species of baculoviral pp56lck are not only differentially phosphorylated (on serine and tyrosine residues) but also heterogeneously myristylated. Surprisingly a non myristylated, very active form of bv-pp56lck is found in the cytoplasm of Sf9 cells. Fractionation of T cells reveals that cytoplasmic pp56lck exists in T lymphocytes as well. PMID- 1911541 TI - Generation of B lymphocytes from a single hemopoietic progenitor cell in vitro. AB - The first stages of the pathway by which lymphocytes differentiate from hemopoietic stem cells were studied at a clonal level. When 211 interleukin 3 (IL 3)-induced blast colonies shown to be capable of differentiating into a variety of hemopoietic cells were individually transferred into wells containing a monolayer of stromal cells, growth in granulocyte, macrophage, megakaryocyte, or mast cell lineages was observed in 192 wells. In seven of these 192 wells, lymphoid cell growth also was seen. The lymphoid cells were proved to be B lymphocytes by phenotype and immunoglobulin gene rearrangement analyses and by demonstration of surface expression of IgM. The clonal origin of myeloid and B lymphocyte lineage cells was further confirmed by the generation of both myeloid and B lymphoid cells in the same well following FACS clone-sorting of IL-3 induced blast cells. These results provide in vitro evidence that cells of B lymphoid and myeloid lineage can originate clonally from single primitive hemopoietic stem cells. PMID- 1911542 TI - Independent rearrangement of Ig lambda genes in tissue culture-derived murine B cell lines. AB - Rearrangement of the lambda light chain locus is considered a late event in pre-B cell differentiation which occurs after successful heavy chain and unsuccessful kappa light chain rearrangement. However, this view has recently been challenged by the observation of apparently independent lambda rearrangement in certain B cell lines and Ig transgenic populations. In this study we have examined the pattern of Ig rearrangements and expression in several tissue culture-derived murine B cell lines. One pre-B cell line (BDL-1) displayed germline heavy and kappa light chain genes despite the presence of a productive lambda 1 light chain rearrangement. Two other cell lines (DAC-2, BDL-2) had multiple lambda rearrangements despite the presence of productive kappa chain rearrangements. These cell lines provide new precedents for rearrangement of the lambda locus independent of the kappa locus. Their phenotype suggests that accessibility at the different Ig loci may be controlled by a non-sequential mechanism. PMID- 1911543 TI - Comparative analysis of CD8 expressed on mature CD4+ CD8+ T cell clones cultured with IL-4 and that on CD8+ T cell clones: implication for functional significance of CD8 beta. AB - Interleukin (IL-4) can induce CD8 expression on mature CD4+ T cells. To study this phenomenon in more detail, we characterized CD8 expressed on IL-4-induced CD4+ CD8+ (double positive) T cell clones in comparison with that on CD8+ T cell clones. Using 2ST8-5H7 mAb that detects CD8 beta expression, we found that double positive T cell clones isolated with IL-4 express CD8 alpha but not beta, in contrast to CD8+ CTL cell clones, which express both chains of CD8. Northern blot analysis revealed that these double positive clones expressed CD8 alpha but not beta mRNA, indicating that CD8 alpha and beta are independently regulated at the pre-translational level. Immunoprecipitation experiments showed that CD8 expressed on a representative IL-4-induced double positive T cell clone consists mainly of homodimers of a single 34 kd protein of CD8 alpha. The amount of multimers detected from this clone was much less than that from a CD8+ CTL clone. These results suggest that persistent expression of CD8 beta is specific for the CD8+ lineage and may be involved in polymerization and stabilization of CD8 which enhances the efficiency of class I-restricted antigen recognition. PMID- 1911544 TI - Complexity of the immunoglobulin light chain V kappa 1 gene family in the New Zealand black mouse. AB - The immunoglobulin light chain V kappa 1 gene family is polymorphic in murine inbred strains and this family has been subdivided into five sub-groups (V kappa 1A-E). The V kappa 1A sub-group contributes to approximately 2% of the total serum immunoglobulin light chains in several mouse strains. However, it has been reported that this sub-group is absent in New Zealand Black (NZB) mouse serum. Amino acid sequencing of myeloma proteins from this inbred mouse has shown that they belong to the V kappa 1B sub-group. We report here the structure of nine functional germline genes from NZB mice that have high homologies to the V kappa 1A, V kappa 1B, V kappa 1C, and V kappa 1D sub-groups. In addition, a novel germline gene representing the prototype of a new sub-group (designated V kappa 1F) has been identified. We have isolated different V kappa 1 germline genes from a single restriction fragment length polymorphism (RFLP) fragment, as well as identical V genes from two different RFLP migrating bands. Therefore, the complexity of the genes encoding the immunoglobulin variable region cannot be determined solely by RFLP analysis. Nucleotide sequence analysis of 16 V kappa 1 genes which code for NZB autoantibodies indicate that they belong to five different V kappa 1 sub-groups with five hybridomas (31%) expressing the V kappa 1A sub-group. Comparison of the sequences of V kappa 1 genes expressed in hybridomas with corresponding germline genes show no somatic mutations. PMID- 1911545 TI - Predominant recognition of human T cell leukemia virus type I (HTLV-I) pX gene products by human CD8+ cytotoxic T cells directed against HTLV-I-infected cells. AB - We established long-term cell lines of cytotoxic T lymphocytes (CTL) specific for human T cell leukemia virus type I (HTLV-I) from peripheral blood lymphocytes (PBL) of a patient with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP), an HTLV-I-carrier with Sjogren syndrome, and an asymptomatic HTLV-I carrier, by repeated stimulation with autologous HTLV-I-infected T cells in vitro. CTL derived from the patient with HAM/TSP expressed CD8 antigen, and their function was restricted by HLA-A2. They showed cytotoxic effects predominantly against the target cells expressing HTLV-I p40tax among the autologous B cell lines infected with vaccinia recombinants containing various HTLV-I genes which served as targets. These data are consistent with the previously reported findings that fresh PBL of HAM/TSP patients contain p40tax-specific CTL activity. Furthermore, CTL derived from the patient with Sjogren syndrome without neurological involvement also demonstrated cytotoxicity predominantly to p40tax. The cytotoxicity to the target cells experimentally expressing p40tax was blocked by unlabeled HTLV-I-infected cells possessing HLA-A2. HTLV-I-specific cytotoxicity was also inhibited by unlabeled B cells bearing p40tax. Thus, HTLV-I p40tax-specific cytotoxicity is mediated by the major CTL population activated by native HTLV-I antigens in patients with HAM/TSP or Sjogren syndrome. In contrast to the CTL of these patients, CTL similarly induced from the asymptomatic HTLV-I carrier, which were highly cytotoxic to autologous HTLV-I-infected T cells, did not show significant levels of cytotoxicity to autologous B cells expressing p40tax.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1911546 TI - The specificity of alloreactive T cells is determined by MHC polymorphisms which contact the T cell receptor and which influence peptide binding. AB - The separate contributions to allorecognition of peptide-binding and T cell receptor-contacting residues of an allogeneic HLA-DR molecule were investigated by site-directed mutagenesis. Alloreactive T cell clones were generated from a combination of responder (DR1Dw1,DR4Dw14) and stimulator (DR1Dw1, DR4Dw10) whose DR products differed at only three amino acid positions, two of which are predicted to interact with the T cell receptor (67 and 70), and one with bound peptide (71). Transfected murine DAP.3 cells expressing the wild type and mutated forms of DR4Dw10 in which the codons for residues 70 and/or 71 had been altered towards DR4Dw14 were used to stimulate a panel of anti-DR4Dw10 T cell clones. Substitutions at either position 70 or 71, or the combination of the two, led to loss of recognition by the alloreactive T cell clones. This implies that residues involved in peptide binding and residues involved in interaction with the T cell receptor are important for this panel of alloreactive T cell clones. The specificity of these alloreactive T cells for exposed polymorphic residues on the allogeneic MHC molecule was further demonstrated by the inhibitory effects of synthetic peptides, derived from the alpha-helix of the beta 1 domain of the DR4Dw10 molecule. PMID- 1911547 TI - Phosphorylation of murine CD8 alpha is not essential for responses of T cell hybridomas to antigen. AB - CD8 T cell differentiation antigens, expressed on class I-restricted T cells, have a key role in the control of recognition and response of these cells to antigen. It has been suggested that these molecules function as co-receptors together with antigen-specific T cell receptors to regulate T cell responses. We have addressed the question of whether cytoplasmic serine phosphorylation, which occurs on CD8 molecules after activation by antigen or phorbol esters, is relevant to its co-receptor function. By mutagenesis, we show that phorbol ester induced phosphorylation occurs exclusively on CD8 alpha serine residue 216. However, inhibition of CD8 polypeptide phosphorylation does not appear to have a detrimental effect on several responses of CD8-dependent transfectants to antigen. This is in contrast to results reported with CD4 (N.Glaichenhaus, N.Shastri, D.R. Littmann and J.M.Turner. 1991. Cell, 64:511), suggesting that CD4 and CD8 molecules may play somewhat different roles in the control of T cell activation. PMID- 1911548 TI - A nuclear factor NF-GM2 that interacts with a regulatory region of the GM-CSF gene essential for its induction in responses to T-cell activation: purification from human T-cell leukemia line Jurkat cells and similarity to NF-kappa B. AB - Activation of T cells by antigen, lectin, or a combination of phorbol-12 myristate acetate (PMA) and calcium ionophore (A23187) leads to the induction of genes for a set of lymphokines, including granulocyte-macrophage colony stimulating factor (GM-CSF). We demonstrated in earlier studies that the upstream region of the mouse GM-CSF promoter at positions between -95 and -73 is essential for transcriptional activation in response to PMA/A23187. This region contains two DNA-binding motifs, GM2 and GC-box. The GM2 sequence (GGTAGTTCCC) is recognized by an inducible factor NF-GM2; the other (CCGCCC) by constitutive factors A1, A2, and B. To elucidate the mechanism of GM-CSF gene activation, we have purified the inducible factor NF-GM2 from the nuclear extract of stimulated Jurkat cells on the basis of specific DNA-binding activity. The purified NF-GM2 consists of 50 (p50) and 65 kDa (p65) polypeptides and has a binding activity specific for both the GM-CSF and immunoglobulin kappa (GGAAAGTCCC) enhancers. Electrophoretically purified p50 alone can form a protein-DNA complex, but in the mixture, p50 associates preferentially with p65 to form the NF-GM2 complex. In addition, p65 gave per se, with low affinity, a protein-DNA complex that migrated more slowly than native NF-GM2 complex. Furthermore, an antiserum against KBF1 (identical to 50 kDa NF-kappa B protein) reacted with the p50 of NF-GM2, indicating that the NF-GM2 polypeptide cannot be immunologically differentiated from the 50 kDa subunit of NF-kappa B. The purified NF-GM2 activated in vitro transcription from the kappa B enhancer, while it failed to stimulate transcription from the GM-CSF promoter harboring the GM2 sequence. This suggests that the activation mechanism of the GM-CSF gene through the GM2/GC-box sequence is different from that of genes carrying the kappa B enhancer alone. PMID- 1911549 TI - Clonal analysis of differential lymphokine production in peptide and superantigen induced T cell anergy. AB - A failure of T lymphocytes to produce interleukin 2 (IL-2) on restimulation may, in part, account for the specific unresponsiveness that accompanies incomplete activation. The evidence to support this has been derived predominantly from the investigation of the molecular basis of anergy in murine type 1 T cells. In this study, the effects of different tolerogenic signals delivered by specific peptide or Staphylococcus aureus enterotoxin on the ability of antigen-specific human T cells to produce lymphokines, both in the induction phase and in established antigen-specific non-responsiveness, have been examined. Although T cell proliferation was decreased by supraoptimal concentrations of specific peptide in the presence or absence of antigen presenting cells, IL-2, IL-4, and interferon gamma (IFN-gamma) synthesis were comparable to that of activated T cells. The different tolerogenic signals, all capable of inhibiting phase of unresponsiveness. Restimulation of anergic T cells with an antigenic challenge failed to induce lymphokine production, with the exception of allergen-reactive T cells that secreted IFN-gamma. This latter observation is relevant to the desensitization of specific responsiveness in allergic disease. PMID- 1911550 TI - IL-3 facilitates lymphocyte hexose transport by enhancing the intrinsic activity of the transport system. AB - Interleukin 3 (IL-3) promotes the survival and proliferation of hematopoietic cells of various lineages in culture. Like most other hematopoietic colony stimulating factors, its mode of action is unknown. However, binding of the lymphokine induces protein tyrosine phosphorylation and enhanced glucose transport in some myeloid progenitor cells. We have studied the hexose uptake following IL-3 stimulation in IL-3-dependent pro-B cells. IL-3 facilitated the uptake of 2-deoxyglucose within 15 min. Kinetic analysis of the 2-deoxyglucose uptake attributed the enhanced transport to improved transporter function, while other hormones or cytokines affect glucose transport primarily via the number of cell surface transporters. PMID- 1911552 TI - I-E-restricted monoclonal expansion of B lymphocytes in the thymus of NOD mouse. PMID- 1911551 TI - Local structure of a peptide contact site on Ak alpha. AB - We have sought to determine how much amino acid diversity is tolerable at position 69 of the Ak alpha chain, a position previously implicated as a peptide contact site. Slot-machine mutagenesis was used to create a set of 11 mutant Ak alpha cDNAs, each specifying a different amino acid at position 69. These cDNAs were individually expressed in L cells together with a wild-type Ak beta cDNA to produce a panel of mutant antigen-presenting cell lines. The ability of each member of this panel to present a hen egg lysozyme and a bovine ribonuclease peptide to various T hybridomas was assessed. We found that a surprising degree of amino acid diversity is tolerable at Ak alpha position 69: even charged (Glu, Arg) or bulky (Trp, Tyr) residues can be accommodated without abrogating cell surface expression of Ak, peptide binding to it, or T cell recognition of it. We discuss the implications of these findings for models of T cell recognition of the class II molecule/antigen duplex. PMID- 1911553 TI - Structure, function and flexibility of human lactoferrin. AB - X-ray structure analyses of four different forms of human lactoferrin (diferric, dicupric, an oxalate-substituted dicupric, and apo-lactoferrin), and of bovine diferric lactoferrin, have revealed various ways in which the protein structure adapts to different structural and functional states. Comparison of diferric and dicupric lactoferrins has shown that different metals can, through slight variations in the metal position, have different stereochemistries and anion coordination without any significant change in the protein structure. Substitution of oxalate for carbonate, as seen in the structure of a hybrid dicupric complex with oxalate in one site and carbonate in the other, shows that larger anions can be accommodated by small side-chain movements in the binding site. The multidomain nature of lactoferrin also allows rigid body movements. Comparison of human and bovine lactoferrins, and of these with rabbit serum transferrin, shows that the relative orientations of the two lobes in each molecule can vary; these variations may contribute to differences in their binding properties. The structure of apo-lactoferrin demonstrates the importance of large-scale domain movements for metal binding and release and suggests that in solution an equilibrium exists between open and closed forms, with the open form being the active binding species. These structural forms are shown to be similar to those seen for bacterial periplasmic binding proteins, and lead to a common model for the various steps in the binding process. PMID- 1911554 TI - Domains in proteins and proteoglycans of the extracellular matrix with functions in assembly and cellular activities. AB - Most proteins of the extracellular matrix (ECM), such as the glycoproteins, collagens and proteoglycans, consist of many structurally autonomous domains that are often functionally distinct. Consequently these proteins are designated as mosaic proteins. Related domains are often found in several different ECM proteins. Domains which are of importance for assembly have been identified by fragmentation and other approaches. Triple-stranded coiled-coil domains in laminin and probably also in tenascin and thrombospondin are responsible for chain selection, a process which may be important for the formation of tissue specific isoforms. Globular domains at the C-terminus of collagenous domains are essential for the registration of the three chains and triple-helix formation. Fibrillar assemblies of these triple helices with constituent globular domains serve important assembly functions in many collagens including collagens IV and VI. Many other domains with more specialized functions in assembly have been identified in laminin, fibronectin and other ECM proteins. Cys-rich domains with either distant or close homology with epidermal growth factor are repeated manifold in rod-like regions of a number of ECM proteins including laminin, tenascin and thrombospondin. They may serve as spacer elements but as suggested for laminin some domains of this type may also function as signals for cellular growth and differentiation. Another important cellular function common to many ECM proteins is cell attachment. Several cell attachment sites have been localized in structurally unrelated domains of the same or of different ECM proteins. PMID- 1911555 TI - Sequence specific thermal stability of the collagen triple helix. AB - Theoretical calculations of the thermal stability of collagen triple helices using empirical values for the contribution of individual tripeptide units are presented and compared with direct measurements of the thermal stability of various types of collagens. Relative stabilities are assigned to the positions of the tripeptide units in the amino acid sequence along the length of the collagen molecule. The sequence specific relative stabilities of type I and type XI collagens are compared. These offer insight into the reasons for the existence of unfolding intermediates in type XI collagen that are absent in type I collagen. The pattern of relative stabilities calculated for mouse type IV collagen is consistent with experimental results which indicate that the amino terminal region is very stable and that the interruptions cause increased flexibility and independently unfolding domains. Mutations in the triple helical domain of human type I procollagen occurring in brittle bone disease (osteogenesis imperfecta) show varying effects on the thermal stability of the molecule. The sequence specific thermal stability calculations shed some light on why some mutations of cysteine for glycine have greater effects on the thermal stability than others. PMID- 1911556 TI - Proteoglycan: collagen interactions in connective tissues. Ultrastructural, biochemical, functional and evolutionary aspects. AB - Electron histochemical investigations of mammalian and echinoderm tissues, using cupromeronic blue to stain proteoglycans (PGs) specifically in critical electrolyte concentration methods, showed that collagen fibrils are associated with keratan sulphate and chondroitin (dermatan) sulphate ('tadpole') PGs at the a, c, d and e bands on the fibril surface, giving rise to the 'one proteoglycan: one binding site' hypothesis. Intra-fibrillar PGs have been observed, distributed in a regular way which suggests that collagen fibrils are aggregates of 'protofibrils', some of which carry PGs at their surfaces. A scheme for remodelling of collagen fibrils, based on recycling of these protofibrils, is outlined. The choice of which tadpole PG to use to carry out a given function is decided to a considerable extent by the availability of oxygen to the relevant tissue element. PMID- 1911557 TI - Morphometric evaluation of collagen fibril dimensions in expanded human breast skin. AB - A great innovation in plastic surgery in recent years has been skin expansion, which has provided the discipline with new possibilities for skin reconstruction. At present, little is known about the biology of skin expansion although it is clear that cell proliferation occurs both in the epidermis and the dermis. During previous morphological investigations of skin under expansion we recorded a number of signs comparable with those seen in wound healing. In the present study, the collagen fibril diameter of of skin before and under expansion has been recorded using an IBAS computer-based morphometric system. Preferentially, we have studied the papillary dermis where the most conspicuous morphological events occur. PMID- 1911558 TI - Thermal denaturation of whey proteins and its effect in dairy technology. AB - The irreversible denaturation of the most important whey protein fractions, namely beta-lactoglobulin A and B and alpha-lactalbumin were studied. The orders of the reactions, the rate constants and the activation energies were determined. The experiments were extended to include whey protein solutions of different concentrations and mixtures of whey proteins and caseins in different proportions. The kinetic data found by experiment make it possible to calculate in advance the precise degree of irreversible denaturation. It was found that the denaturation of beta-lactoglobulin was a good test parameter in technological studies and that there was a close correlation between the degree of denaturation and the results of important dairy processes. PMID- 1911559 TI - Spatial disorders and computational cures. AB - Image averaging provides a powerful method for enhancing the yield of interpretable information from electron micrographs of biological macromolecules. However, as originally conceived, the full benefit of averaging is achieved only with perfectly ordered two-dimensional crystals. More recent developments, reviewed here, allow one to rectify disordered lattices, straighten randomly bent filaments, and combine multiple images of free-standing particles, thus extending the advantages of image averaging to virtually every class of macromolecular specimen. PMID- 1911560 TI - Some biophysical applications of motional contrast in n.m.r. microscopy. AB - The principal advantage of the n.m.r. imaging method lies in the specific contrasts which are available. In this work we describe the use of velocity and diffusion contrast methods in biophysical applications and at microscopic spatial resolution. In the first example, involving water-protein interactions, the relationship between water self-diffusion and water concentration, as measured using pulsed gradient spin echo n.m.r., is shown. It is demonstrated that this relationship can be used to provide a water concentration image. The result is compared with the conventional proton density and transverse relaxation maps. The next example concerns the use of dynamic n.m.r. microscopy to obtain water diffusion and velocity maps for wheat grain in vivo. Finally we suggest how the method may be used in the study of polymer-water interactions in an unusual adjunct to conventional polymer self-diffusion studies. PMID- 1911561 TI - Environmetric time-series analysis: modelling natural systems from experimental time-series data. AB - Using the modelling of solute transport in flowing media as an example, this paper outlines the main aspects of a systematic approach to the modelling of natural systems from experimental time-series data. The objective of the approach, which exploits sophisticated methods of recursive parameter estimation, is to produce a parametrically efficient, data-based model which is both physically meaningful and statistically well defined. Although the proposed methodology has its origins in systems and control theory and may be unfamiliar to some natural scientists, it has been developed and refined for use with natural environmental systems over the past 20 years, and has wide application potential in areas such as biology and ecology. In this sense, the paper is intended to introduce the more general reader to the topic, in the hope that the tutorial review and practical examples will stimulate interest and encourage reference to the many publications cited in the paper. The practical examples are concerned with the modelling of pollutant dispersion in stream channels: phloem translocation and carbon partitioning in plants: and rainfall-streamflow modelling in a river catchment. PMID- 1911562 TI - Effects of disorder on fibre diffraction patterns. AB - Diffraction patterns from oriented polycrystalline specimens of fibrous polymers sometimes contain features indicating that the constituent microcrystallites are disordered. Such disorder affects the relationship between the crystal structure and the diffracted intensities. Therefore, the effects of disorder must be considered when determining structures from fibre diffraction data. Theory is developed here that describes the intensities diffracted by disordered polycrystalline fibres, and is used to calculate diffraction patterns from stimulated specimens with various kinds of disorder. The results show how Bragg and continuous diffraction are distributed on such diffraction patterns, and implications for structure determination are discussed. PMID- 1911563 TI - A commentary on an association of malignant melanoma with non-ultraviolet radiation exposure. AB - There are direct and indirect studies that suggest that non-ultraviolet radiation may be associated with the increasing mortality and incidence of malignant melanoma of the skin. Tangential and supporting evidence for these associations are critically reviewed. PMID- 1911564 TI - Contact sensitivity to mercuric chloride is associated with I-A region in mice. AB - Genetic control of contact sensitivity to mercuric chloride antigen was studied using various strains on inbred mice. Mice with class II Ab,d,f,s haplotypes showed a high magnitude of response, whereas those with class II Ak,q were low responders. These results indicate that mercuric chloride contact sensitivity may be influenced by the I-A region of H-2. Transfer experiments revealed that these responses might be mediated by L3T4+, Lyt-2- T cells. However Lyt-2+ T cells do not suppress the DTH response. PMID- 1911565 TI - Effects of cyclosporin A on cell proliferation and collagen production by human skin fibroblasts. AB - Cyclosporin A (CSA) is a potent immunosuppressive drug that has been used clinically for the treatment of organ rejection after transplantation as well as for patients with a wide variety of immune-mediated disorders. CSA has recently been reported to be effective in systemic sclerosis, which is a disease of the connective tissues leading to fibrosis of the skin and other involved organs. In this study, we investigated whether CSA affects the cell proliferation and collagen synthesis of human skin fibroblasts. CSA inhibited the DNA synthesis and cell growth of cultured fibroblasts at concentrations of 10(-8) M to 10(-5) M in a dose-dependent manner. The production of both collagen and non-collagenous protein at both the mRNA and protein levels was not affected by 10(-8) to 10(-6) M CSA, but was decreased in the presence of 10(-5) M CSA. These results suggest that CSA may inhibit the proliferation of fibroblasts, but not their synthesis of collagenous and non-collagenous proteins at therapeutic concentrations. PMID- 1911566 TI - Cytokines alter mRNA steady state levels for basement membrane proteins in human skin fibroblasts. AB - Keratinocytes and fibroblasts synthesize basement membrane proteins and even contribute to the formation of basement membrane structures following injury or tissue damage. Under these conditions many cellular functions are regulated by mediators e.g. transforming growth factor-beta, tumor necrosis factor alpha, interferon-gamma or interleukin-1 alpha. We therefore describe here their influence on synthesis of basement membrane proteins in human skin fibroblasts. A comparative analysis of mRNA steady levels coding for BM-40, nidogen, laminin B1 and B2 chains and collagen IV in fibroblasts, in primary human keratinocytes and a epidermal cell line grown in monolayer culture demonstrated that the highest amounts were present in human fibroblasts. Interferon-gamma reduces all mRNA steady state levels dose dependently in comparison to the control, while transforming growth factor-beta simultaneously induces BM-40, alpha 1 and alpha 2 (IV) collagen mRNAs. TGF-beta, however, has no effect on nidogen and laminin mRNA levels. Interleukin-1 alpha and tumor necrosis factor alpha do not affect the mRNA levels of most basement membrane proteins. However, the alpha 1 (IV) collagen mRNA is upregulated by both cytokines to 300%. These data demonstrate a specific control of the expression of several basement membrane proteins by cytokines and indicate that fibroblasts could contribute to basement membrane formation during wound healing and tissue repair. PMID- 1911567 TI - Collagen mRNA expression detected by in situ hybridization in keloid tissue. AB - The keloid fibroblasts exhibited increased extracellular matrix gene expression, and prominent elevated type I procollagen mRNA when compared to control fibroblasts cultured from the uninvolved skin of normal people. It also showed markedly elevated type I/III procollagen mRNA ratios, but no synthesis of type IV procollagen mRNA by keloid fibroblasts was observed. By in situ hybridization in keloid tissue, high levels of type I and type III procollagen mRNAs were detected in most of the fibroblasts, suggesting the presence of a subpopulation responsible for the increased collagen production. The levels of type I and type III procollagen mRNAs in these fibroblasts were clearly elevated compared to control skin specimens. And concentration of type I procollagen mRNA was found more predominantly than was type III. These results suggest that deposition of collagen in keloid could result from activation of certain fibroblasts responsible for type I procollagen production. PMID- 1911569 TI - Changes in vascular surgery: a window on the future. PMID- 1911568 TI - Intestinal permeability in patients with psoriasis. AB - A possible relationship between intestinal structure and function in the pathogenesis of psoriasis has recently brought about considerable interest. The purpose of this study was to evaluate the intestinal permeability in psoriatic patients by comparing it with healthy controls. 15 psoriatic patients and 15 healthy volunteers entered the study. Intestinal permeability was evaluated using the 51Cr-labeled EDTA absorption test. The 24-h urine excretion of 51Cr-EDTA from psoriatic patients was 2.46 +/- 0.81%. These results differed significantly from controls (1.95 +/- 0.36%; P less than 0.05). The difference in intestinal permeability between psoriatic patients and controls could be due to alterations in the small intestinal epithelium of psoriatics. PMID- 1911570 TI - Ethical aspects of the use of animals in research. PMID- 1911571 TI - Excimer laser radiation for endarterectomy of experimental atheromas. AB - Open laser endarterectomy produces a smooth arterial surface with welded distal end points. This report evaluates 308-nm excimer laser radiation for the laser endarterectomy operation. Arteriosclerotic New Zealand white rabbits (N = 15) were studied. A thoraco-abdominal exploration was performed, the aorta was isolated, heparin was administered, and multiple endarterectomies were performed in each rabbit. A line of laser craters was created at the proximal and distal ends of an atheroma. Laser radiation was used to connect the craters to form the proximal and distal end points. The atheromas were dissected from the aorta with laser light and the end points were fused. The aortas were removed for light and electron microscopy and the animals were sacrificed. Excimer radiation was delivered by a 600-microns fiber at 50 mJ/pulse, 120-ns pulses and either 15- or 20-Hz frequency. At 15 Hz excimer laser endarterectomies showed no perforations along the surface or at the end points. The surfaces were smooth but the end points were not welded in place. At 20 Hz, perforations were seen along 7/11 surfaces and at 5/11 end points. Excimer laser endarterectomy is best performed at 15 Hz. The end points, however, cannot be welded with excimer laser radiation. PMID- 1911572 TI - Effect of massive small bowel resection on gastric acid secretion in the rat. AB - The phenomenon of a transitory gastric acid hypersecretory state after extensive bowel resection is well established. Its time of onset, however, is unknown. The purpose of this study was to determine the immediate effect of massive small bowel resection (MSBR) on gastric acid secretion (GAS). An anesthetized innervated rat model was prepared with gastric and jugular cannulae. Three groups of animals were studied: group I (n = 12), basal unstimulated state; group II (n = 12), pentagastrin (Pg) 16 micrograms/kg h-1 stimulated; and group III (n = 16), 5% liver extract meal (LEM) stimulated. Each group consisted of experimental animals that underwent 95% MSBR from proximal jejunum to terminal ileum and control animals that remained intact. Acid output was determined by extragastric titration with 0.1 M NaOH. Blood was taken for basal and postprandial serum gastrin levels. Basal acid output (mueq/10 min) significantly increased immediately after MSBR in all groups (p less than .01). Ninety minutes following MSBR, acid outputs were significantly elevated in basal and Pg-stimulated but not LEM-stimulated rats. Serum gastrin increased from 30 +/- 1 to 56 +/- 6 pg/mL (p less than .01) in group I rats and from 81 +/- 28 to 129 +/- 13 pg/mL in group III rats (p = NS). We conclude that GAS increases immediately after MSBR in group I and II rats. This increase in GAS may be mediated by gastrin release. PMID- 1911573 TI - Modification of the thrombogenicity of a self-expanding vascular stent. AB - When placed in the iliac arteries of normal healthy animals, the Wall-stent self expanding endovascular prosthesis exhibits minimal thrombogenicity, measured by 111In-labeled platelet uptake. Preliminary clinical reports suggest a greater thrombogenicity in diseased human arteries. When evaluated in an ex vivo shunt, these stents exhibit significant thrombogenicity. The ex vivo shunt may therefore provide a model to evaluate strategies to reduce thrombogenicity in the clinical setting. Stents were released into shunts and the uptake of In111-labeled platelets was measured by gamma imaging for 2 h at a flow rate of 100 mL/min. The effect of systemic heparin, 100 U/kg, oral aspirin, 325 mg, and local application of heparin-benzalkonium chloride complex were evaluated. At the end of each study the stents were fixed in situ and evaluated with scanning electron microscopy (SEM). Control stents exhibited a rapid, significant uptake of platelet associated 111In activity, which reached a maximum in approximately 1 h. Twenty two percent of control stents occluded before 2 h. Aspirin reduced maximum platelet uptake by 46%. Systemic heparin, with a clotting time greater than five times control, reduced maximum platelet uptake by 86%. The benzalkonium-heparin complex coating, with no increase in clotting time, reduced maximum platelet uptake by 84%. No occlusions were observed with the anti-thrombotic regimes. SEM evaluation of the stents supports the results of the isotope uptake studies. PMID- 1911574 TI - Effects of temperature and viscosity on prothrombin times of blood. AB - Accurate prothrombin time tests are important because they are frequently performed on presurgical patients to evaluate their blood-clotting status. We studied the effect of temperature (27-47 degrees C) on PTs obtained with eight different brands of thromboplastin. We also compared the sensitivities of two types of coagulation timers to changes in blood viscosities between 1 and 16 mPa/s. Viscosities were measured with the Brookfield Digital Viscometer. The MLA Eletra 800 and the BBL fibrometer were used to measure PTs. All eight thromboplastins gave convex curves of PT versus temperature, with optimum values lying between 38 and 39 degrees C. The curves were fitted to 4th-degree polynomials which showed that a mean temperature bias of 2 degrees C can increase PTs. Ortho Brain (7.8% change) was affected the most, while thromboplastin C (4.4% change) was affected the least. Plots of PT versus viscosity showed that the BBL fibrometer, which uses an electromechanical sensor, was more affected by viscosity than the MLA Electra 800, with an optical detector. However, above 8.2 mPa/s, all PTs were significantly elevated. Hence, patients with macroglobulinemia, whose plasma viscosities sometimes exceed 8.2 mPa/s, may have falsely elevated PTs. We conclude that temperature and viscosity are critical factors in the test and significantly contribute to within and between laboratory variations in PT measurements. PMID- 1911575 TI - Ethanol injection of hepatic tumors. AB - To assess the efficacy of intratumoral injections of absolute ethanol in the treatment of hepatic tumors, 18 New Zealand White rabbits underwent implantation of two 1-mm3 fragments of the VX-2 carcinoma. The animals were reexplored 2 weeks postimplant and the tumors measured. One nodule was treated by intratumoral injections of 2.28 +/- 0.72 mL of absolute ethanol; the second was injected with an equal amount of normal saline. The animals were sacrificed 4 weeks postimplant, and the tumors were measured and microscopically examined. On gross inspection, tumor size, expressed as the product of the largest and smallest diameters, was 4.59 +/- 3.4 cm2 for the ethanol-injected tumors vs 6.73 +/- 2.1 cm2 for the saline-treated nodules (p = .01). Histologic sections through the largest tumor diameter were microscopically examined using a computerized image analyzer. The mean cross-sectional area of viable tumor was 0.51 +/- 0.3 cm2 for the ethanol-treated nodules vs 2.01 +/- 0.5 cm2 for the saline-treated nodules (p less than .001). Contrast-enhanced CT and MRI studies were able to provide valuable information in terms of tissue characterization, which will be useful in differentiating viable tumor from necrotic tumor and infarcted liver. We conclude that intratumoral ethanol injection inhibits growth of liver tumors in this experimental model and deserves further study. PMID- 1911577 TI - Preliminary study of the protective effect of the calcium channel blocker, nifedipine, on adriamycin-induced tissue injury. AB - The effect of nifedipine, an oral calcium-channel blocker, on adriamycin-induced wound healing was studied. Nifedipine was administered to animals prior to treating with adriamycin. The healing strengths of cecal, fascial, and skin anatomoses were measured. Animals treated with adriamycin alone had significant decreases in healing strength compared to controls: for cecum at postoperative days (POD) 7 and 14; for skin at PODs 14, 21, and 28; for fascia at POD 28. Overall, nifedipine reduced the impact of adriamycin injury on the strength of healing incisional anastomoses. Nifedipine also appeared to protect collagen synthesis at anastomotic sites from adriamycin-induced impairment. PMID- 1911578 TI - Effect of allopurinol on adriamycin-induced impairment of wound healing. AB - Use of antineoplastic drugs perioperatively requires an understanding of their potential effects on healing wounds. Adriamycin is an antineoplastic drug with a wide range of antitumor activity. Prior studies have demonstrated that adriamycin impairs skin wound healing but these studies have offered limited explanations for the mechanism of action of the drug vis a vis impairment of healing wounds. In this study we investigated the effect of a xanthine oxidase inhibitor, allopurinol, on adriamycin-induced tissue injury to determine the role oxyradicals might play in reducing wound-breaking strength. Sixty-four Buffalo rats were studied. Eight animals were used to establish drug tolerances. Fifty six animals were divided into four experimental groups; saline control (2 mL IP), allopurinol control (4.3 mg/kg po), allopurinol-adriamycin (4.3 mg/kg po + 6 mg/kg IV, respectively), and adriamycin (6 mg/kg IV). Animals treated with adriamycin alone had significantly reduced weight at postoperative day (POD) 7 compared to control groups (p less than .025). Bowel-bursting strength (BBS) of the animals treated with adriamycin alone was also significantly decreased at POD 7, compared to controls (p less than .025), and by POD 14 the animals treated with adriamycin alone had a significantly decreased fascial tensile strength, compared to the saline control (p less than .05). At no point did the animals treated with both allopurinol and adriamycin show a significantly decreased weight, BBS, or fascial tensile strength compared to control animals. Allopurinol appeared to protect against adriamycin toxicity on healing wounds. These results suggest that xanthine oxidase and possibly superoxide radicals play an important role in mediating adriamycin toxicity on healing wounds. PMID- 1911576 TI - Effects of hypercholesterolemia on healing of vascular grafts. AB - Small-diameter vascular grafts woven from bioresorbable lactide/glycolide copolymers have been successfully interposed into aortas of normal NZW rabbits. The current study examines the histologic and functional reactions to these bioresorbable grafts in severely hypercholesterolemic rabbits, a standard animal model of atherosclerosis. Sixty rabbits were placed on a 2% cholesterol, 6% peanut oil atherogenic diet. Baseline serum cholesterols and triglycerides were measured and repeated at operation 3 months later. Woven polyglactin 910 (PG910) grafts were interposed into infrarenal aortas. Fifty-two rabbits died on the diet or within 3 days of surgery and eight survived operation (normal NZW rabbit operative mortality is less than 10%). Cholesterol levels rose from 63 to 1989, p less than .001. Of the eight survivors, five died after 3 weeks, and one died after 2 1/2 months. Two were sacrificed at 2 and 4 months. Four aortic disruptions with retroperitoneal hematomas, one pseudoaneurysm, and one diffuse aneurysm were observed, greater than in normal rabbits, p less than .001. Inspection revealed severe atherosclerosis. Histologically, 3-week explants showed only small areas of neointima with myofibroblasts and endothelial cells; the outer capsules were infiltrated by lipid-laden macrophages. Graft material in 2- to 4-month explants was replaced by tissue with histologic atherosclerosis. More severe atherosclerosis was observed in native aortas at the perianastomotic areas than the more distant aortic segments. Abundant intracellular lipid was seen also in splenic histiocytes and hepatic cells with evidence of micronodular cirrhosis. Macrophages phagocytizing bioresorbable prostheses may release growth factors mediating the formation of a cellular tissue conduit. Severe hypercholesterolemia may alter monokine release from macrophages resulting in a weakened prosthesis/tissue complex. PMID- 1911579 TI - Assessment of blood flow through the lung using laser Doppler flowmetry. AB - The value of laser Doppler flowmetry in measuring blood flow through the lung was assessed comparing it with flow measured by electromagnetic flowmetry. This was an experimental laboratory-based prospective study performed in an approved University animal research facility. Ten beagle dogs were used. Simultaneous measurement of pulmonary blood flow by laser Doppler flowmetry and electromagnetic flowmetry was carried out at varying degrees of pulmonary artery constriction. There was a linear relationship between the two methods of assessing blood flow (regression equation: y = 0.9x + 5.5; p = .00001) using a least-squares, best fit, straight line analysis (160 data points). The results of this study demonstrate that laser Doppler flowmetry provides an accurate indicator of pulmonary blood flow, which in practice is both simple and reproducible. PMID- 1911580 TI - Progestogens, lipid metabolism and hormone replacement therapy. PMID- 1911581 TI - Fetal heart block associated with maternal anti-Ro (SS-A) antibody--current management. A review. PMID- 1911582 TI - Companionship to modify the clinical birth environment: effects on progress and perceptions of labour, and breastfeeding. AB - OBJECTIVE: To measure the effects of supportive companionship on labour and various aspects of adaptation to parenthood, and thus by inference the adverse effects of a clinically orientated labour environment on these processes. DESIGN: Randomized controlled trial. SETTING: A community hospital familiar to most of the participants, with a conventional, clinically-orientated labour ward. SUBJECTS: Nulliparous women in uncomplicated labour. INTERVENTION: Supportive companionship from volunteers from the community with no medical nor nursing experience, concentrating on comfort, reassurance and praise. MAIN OUTCOME MEASURES: Duration of labour, use of analgesia, perceptions of labour and breastfeeding success. RESULTS: Companionship had no measurable effect on the progress of labour. Diastolic blood pressure and use of analgesia were modestly but significantly reduced. The support group were more likely to report that they felt that they had coped well during labour (60 vs 24%, P less than 0.00001). Their mean labour pain scores (26.0 vs 44.2, P less than 0.00001) and state anxiety scores (28.2 vs 37.8, P less than 0.00001) were lower than those of the control group. Compared with the control group (n = 75), at 6 weeks women in the support group (n = 74) were more likely to be breastfeeding exclusively (51 vs 29%, P less than 0.01); and to be feeding at flexible intervals (81 vs 47%, P less than 0.0001). CONCLUSIONS: Labour in a clinical environment may undermine women's feelings of competence, perceptions of labour, confidence in adapting to parenthood and initiation of successful breastfeeding. These effects may be reduced by the provision of additional companionship during labour aimed to promote self-esteem. PMID- 1911583 TI - Prospective comparison of videopelviscopy with laparotomy for ectopic pregnancy. AB - OBJECTIVE: To compare operative laparoscopy with laparotomy for the management of ectopic pregnancy in haemodynamically stable women. DESIGN: Non-randomized prospective cohort study, treatment allocation depending on the surgical preference and experience of the on-call medical team. SETTING: Provincial undergraduate teaching hospital. SUBJECTS: 87 consecutive and unselected haemodynamically stable women treated for ectopic pregnancy between 1 March 1988 and 31 August 1989. INTERVENTIONS: Salpingotomy, salpingectomy, salpingo oophorectomy or simple extraction of the ectopic pregnancy depending on its site, size and nature performed under laparoscopic control or laparotomy. MAIN OUTCOME MEASURES: Operative outcome, duration of surgery, intra- and post-operative complications, post-operative hospital stay, return to normal domestic activities, return to work, changes in plasma beta-hCG concentrations, health and social service costs. RESULTS: 60 women were treated by videopelviscopy on 65 occasions and the other 27 were treated by laparotomy. The two groups were similar for age, parity and gestation at presentation. Of the 65 operative laparoscopies 61 (94%) were successful and all 27 laparotomies were completed uneventfully. Whereas the operating time was similar in the two groups, 55.3 and 51.1 min for videopelviscopy and laparotomy respectively, operative laparoscopy was associated with significantly shorter post-operative hospital stay (1.7 vs 5.2 days), faster return to domestic activities (1.5 vs 3.3 weeks) and work (2.5 vs 5.7 weeks) (P less than 0.001 for all). In economic terms, successful videopelviscopy was associated with a reduction in hospital accommodation costs by 69% (248 pounds vs 808 pounds), drug costs by 52% (8.38 pounds vs 17.57 pounds) and statutory sickness payment by 51% (130.25 pounds vs 266.51 pounds), that is an overall saving to the health and social services of 701.47 pounds or 50% per ectopic pregnancy (P less than 0.001). CONCLUSIONS: Operative laparoscopy can be used to successfully treat most cases of extrauterine pregnancy with advantages over laparoscopy in terms of reduced hospitalization, faster recovery and lower health service costs. PMID- 1911584 TI - Audit of workload in gynaecology: analysis of time trends from linked statistics. AB - OBJECTIVE: To report on trends in workload patterns in gynaecology using linked statistical data. DESIGN: Retrospective analysis of linked abstracts of hospital inpatient and day case records for patients treated in the National Health Service in gynaecology. SETTING: Six health districts in the south of England covered by the Oxford record linkage study. SUBJECTS: Records for hospital admissions to gynaecology (excluding obstetric admissions) from 1975 to 1985. MEASUREMENT AND MAIN RESULTS: Inpatient episodes increased by 23.5% and day case episodes increased by 13.1%. More people treated contributed about 90% and increased readmissions contributed about 10% to the increase in workload. The workload was decreased by strike action in 1975 and 1981-2. Average length of stay decreased substantially and consistently over the 11 years. Emergency readmissions increased annually by an average of 2.7%. Admission rates in 11 groups of surgical procedures accounting for 85% of all gynaecological inpatients are reported, and increases occurred in 10 of the 11 groups. For example, average increases in annual admission rates were 1.0% for sterilization, 1.9% for legal abortion and 8.2% for biopsy of the cervix, the rate for dilatation and curettage decreased by 1.4%. CONCLUSIONS: The increase in admission rates in gynaecology was almost entirely due to increases in numbers of people treated. The rise would have been even greater if the increase in private patients had been considered. The increase may reflect increased expectations on the part of patients and their doctors, advances in technology and increased bed availability due to declining lengths of stay. PMID- 1911585 TI - Pretreatment of the primigravid uterine cervix with mifepristone 30 h prior to termination of pregnancy: a double blind study. AB - OBJECTIVE: To determine the effect of the antiprogestogen mifepristone (RU 486) on cervical resistance before first trimester termination of pregnancy. DESIGN: Prospective double blind randomized placebo controlled study. SETTING: Department of gynaecology in a university teaching hospital, Sheffield. SUBJECTS: 80 Primigravid women greater than 18 years of age, undergoing termination of pregnancy at between 7 and 13 weeks gestation. INTERVENTIONS: A single dose of 600 mg of mifepristone or placebo given orally 30 h before termination of pregnancy under general anaesthesia. MAIN OUTCOME MEASURES: Cervical resistance to dilatation. RESULTS: Pretreatment with mifepristone significantly reduced the amount of force required to dilate the cervix to 10 mm. In comparison with placebo, the mean sum of the peak forces obtained with dilators 4 to 10 mm was reduced from 84.3 N (SD 29.7) to 46.0 N (SD 26.7). Two women in the treated group had a cervical resistance of greater than 100 N compared with nine women in the placebo group (RR 0.18, 95% CI 0.04-0.89). The 8 mm dilator could be passed with less than 5 N force in 16 women (43%) in the treated group compared with none in the placebo group. Women in the active treatment group had more preoperative pelvic pain and vaginal bleeding but less postoperative pain. CONCLUSION: Mifepristone significantly reduces cervical resistance in the first trimester of pregnancy and produces minimal side effects. PMID- 1911586 TI - Follicular development in spontaneous and stimulated cycles in women with minimal mild endometriosis. AB - OBJECTIVE: To study follicle development in women with minimal-mild endometriosis. DESIGN: In women with endometriosis a spontaneous ovulatory cycle was compared with two subsequent cycles in which either clomiphene or clomiphene and FSH were given to stimulate folliculogenesis. Spontaneous cycles in women with tubal infertility provided a comparison group. SETTING: Infertility clinic, Aberdeen Maternity Hospital. SUBJECTS: 17 women with minimal-mild endometriosis and 10 women with tubal infertility. INTERVENTIONS: The women with endometriosis were treated with 150 mg clomiphene citrate from days 2 to 6 in one cycle and in a subsequent cycle with 150 mg clomiphene citrate on days 2 to 6 plus 75 iu FSH daily thereafter. MAIN OUTCOME MEASURES: Follicular size measured daily using ultrasound. Serum FSH estimated on days 5 and 7 and then daily. RESULTS: Spontaneous follicular growth in the women with endometriosis was similar to that in the women with tubal infertility. Follicular development began earlier in cycles with clomiphene/FSH and the leading follicle reached 16 mm 2 days sooner but the rate of growth was similar whether or not either regimen of stimulation was used. CONCLUSION: Follicular growth is not impaired by minimal-mild endometriosis. Infertility with this condition cannot be explained by altered follicular growth or responsiveness. PMID- 1911587 TI - Outcomes of referrals to gynaecology outpatient clinics for menstrual problems: an audit of general practice records. AB - OBJECTIVE: To determine referral rates and intermediate and long-term outcomes for patients consulting for menstrual disorders and referred by their general practitioner to gynaecology outpatient clinics. DESIGN: General practitioners' records of referrals to outpatient clinics and retrospective audit of general practice notes to determine outcomes. SETTING: General practices in the Oxford Regional Health Authority area referring to 19 gynaecology outpatient clinics. SUBJECTS: 205 patients aged 15-59, referred in 1983/4 and follow up in 1988/9. MAIN OUTCOME MEASURES: Immediate outcomes: the initiation by hospital specialists of investigation, treatment or advice. Five year outcomes: general practice consultation rates and symptom prevalence. RESULTS: Of 18,754 index referrals recorded by 33 practices over a period of 6 months, 2513 (13%) went to gynaecology clinics. Menstrual disorders constituted 21% (n = 539) of the gynaecology referrals; there was more than three-fold variation between the practices in referral rates. In the 5 years following the index referral, of the 205 audited patients 167 (81%) had been admitted to hospital, 91 (44%) had had a hysterectomy (including 87 (60%) of the 145 patients referred for menorrhagia), 98 (48%) had dilatation and curettage; 25 (12%) received only drug therapy; and 10 (5%) had no active treatment for these symptoms from either the specialist or the general practitioner. Only 29 (14%) had consulted their general practitioners about menstrual problems in the 12 months preceding the audit. CONCLUSIONS: Guidelines are needed to assist referral decision-making. If audit is to be used to promote good practice these guidelines should consider the patients' anxieties and preferences, as well as the most appropriate use of investigations and treatments. PMID- 1911588 TI - 'Nuns, virgins, and spinsters'. Rigoni-Stern and cervical cancer revisited. AB - The view that nuns have a very low risk of cervical cancer is questioned. The historical evidence for this view is reviewed, from the beginning of the eighteenth century to the present. An estimate of the actual mortality rate from cervical cancer suggests that risk of death from this neoplasm among nuns is little different from that among the general female population. It is recommended that nuns should not be excluded from cervical cytology screening. When symptoms which might suggest cervical cancer arise in such women, full gynaecological assessment is necessary. PMID- 1911589 TI - Increased plasma levels of vasoactive intestinal polypeptide in pre-eclampsia. AB - OBJECTIVE: To investigate the plasma vasoactive peptide (VIP) levels in pregnancies complicated by pre-eclampsia. DESIGN: A prospective clinical study. SETTING: University Department of Obstetrics, Tromso, Norway. SUBJECTS: 18 women with untreated gestational proteinuric hypertension between 32 and 40 weeks gestation (13 primigravid) and 8 women with normal pregnancies of similar gestational age. INTERVENTIONS: Fasting blood samples on two occasions, 10 min apart. MAIN OUTCOME MEASURES: Plasma VIP measured by radioimmunoassay. RESULTS: Mean maternal plasma VIP was 13.9 (SEM 1.7) pmol/l in those with pre-eclampsia and 4.4 (SEM 0.5) pmol/l in normal pregnancies (P less than 0.0001). CONCLUSION: The increased levels of VIP in pre-eclampsia may represent a powerful compensatory mechanism to restore vascular perfusion of various organs, including the uterus and placenta. PMID- 1911590 TI - Reproducibility of ultrasonic measurement of fetal cardiac haemodynamics. AB - Two observers made independent estimates of volume flow across all four heart valves in 27 fetuses using a combination of cross-sectional and Doppler echocardiography. There were considerable discrepancies between observers in volume flow estimation arising from inconsistency both in cross-sectional and in Doppler measurements. One observer also produced a second estimate by making new measurements from the original recordings. There was considerable within-observer variability which was mainly due to errors in cross-sectional measurements. The problems of applying this technique to fetal cardiac haemodynamics are discussed. PMID- 1911591 TI - Symptoms analysis for the diagnosis of genuine stress incontinence. AB - OBJECTIVE: To determine the accuracy of an analysis of symptoms alone for the diagnosis of genuine stress incontinence. DESIGN: A comparison of results of symptoms analysis with urodynamic findings. SETTING: A gynaecological video urodynamic unit. SUBJECTS: 252 consecutive patients referred for urodynamic investigations. INTERVENTIONS: A questionnaire of 20 symptoms of lower urinary tract dysfunction, midstream specimen of urine, pad testing, uroflowmetry, and video-cystourethrography. MAIN OUTCOME MEASURES: Using the urodynamic diagnosis as the 'gold standard', the accuracy of discriminant function analysis of symptoms was determined. RESULTS: Symptoms analysis achieved a correct classification of 81% with a false positive rate of 16%. Use of an accumulative probability curve defines patients who fall into the equivocal range. CONCLUSIONS: All women presenting with incontinence should undergo preoperative urodynamic studies. PMID- 1911592 TI - Relation of fetal blood gases and data from computer-assisted analysis of fetal heart rate patterns in small for gestation fetuses. AB - Fetal heart rate (FHR) monitoring and computer-assisted analysis were performed immediately before cordocentesis in 25 severely small-for-gestational age fetuses. There were significant associations between FHR variation and both umbilical vein blood PO2 (r = 0.66) and pH (r = 0.69). However, the wide scatter of values around the regression lines prevented accurate prediction of fetal blood gases from FHR patterns. Nevertheless, FHR variation less than 20 ms was always associated with severe fetal hypoxaemia and acidaemia. PMID- 1911593 TI - Computerization of a colposcopy clinic. AB - The first phase of a paperless computer record has been developed at Hammersmith Hospital. The system was designed around the work practices of the clinic staff. In this phase the data are collected on forms which replace the normal case notes. This information is entered onto an IBM compatible computer by the secretary using a quick, user-friendly program written in a dBASE dialect and compiled with Quicksilver. The program produces letters to patients and their doctors and a printed record of the clinic findings for the case sheet to replace the handwritten form. When funding for hardware becomes available the data will be entered directly into the system by the medical staff in the clinic. Clinic appointment lists are maintained and patients "lost to follow-up' can be identified. Ad hoc enquiries can be made using dBASE III Plus or any similar program. This approach has integrated the computerized recording of data in a colposcopy clinic with the normal work of the staff involved so that no extra effort is required from medical or secretarial staff. The immediate accessibility of patient data and the ability to audit the work of the clinic have been particularly useful. PMID- 1911594 TI - Direct antenatal fetal electrocardiographic waveform analysis. AB - OBJECTIVE: To establish a technique for continuous recording of fetal electrocardiograms (ECG) for waveform analysis in the antenatal period. DESIGN: Prospective descriptive study. SETTING: Fetal Medicine Unit, Queen Charlotte's and Chelsea Hospital, London, UK. SUBJECTS: 35 women undergoing antenatal fetal blood sampling. INTERVENTIONS: One end of an insulated Cooner wire was attached to the sampling needle and the other to an automatic ECG-ST waveform analyser. MAIN OUTCOME MEASURES: ECG signals were obtained with the needle in the fetal abdomen during intrahepatic umbilical vein sampling or aspiration of fetal urine but not when it was in the placental cord insertion. RESULTS: Continuous recording of the T/QRS ratio was obtained for a total of 166 min (mean 8 min per fetus) from 20 fetuses (16-38 weeks). The T/QRS ratio had no correlation with gestational age and fetal heart rate and was similar to values described in term fetuses in labour. CONCLUSIONS: The technique described can identify ST waveform changes and may be useful in the investigation of fetal cardiac arrhythmias, intrauterine growth retardation and in monitoring fetal transfusions. PMID- 1911596 TI - CA 125 and preterm prelabour rupture of the membranes. PMID- 1911595 TI - Difficulties in the diagnosis of congenital toxoplasmosis by cordocentesis. Case report. PMID- 1911597 TI - Haematometra secondary to hormone replacement therapy. Case report. PMID- 1911598 TI - Patient selection for hysteroscopic endometrial resection. PMID- 1911599 TI - External cephalic version at term: how high are the stakes? Commentary. PMID- 1911600 TI - Obstetric mortality and its causes in developing countries. PMID- 1911601 TI - Conflicting views on the measurement of blood pressure in pregnancy. PMID- 1911602 TI - Stopping smoking--again. PMID- 1911603 TI - First trimester prenatal diagnosis: chorion villus sampling or amniocentesis? PMID- 1911604 TI - Some historical aspects of toxaemia of pregnancy. A review. PMID- 1911605 TI - Doppler investigation of uteroplacental blood flow resistance in the second trimester: a screening study for pre-eclampsia and intrauterine growth retardation. AB - OBJECTIVE: To assess the screening properties of a mid-trimester uteroplacental Doppler scan in a normal unselected population. DESIGN: A cross-sectional study measuring an averaged resistance index (AVRI) from four sites (left and right uterine and arcuate arteries) with continuous wave Doppler ultrasound. SETTING: Routine booking ultrasound, King's College Hospital, London. SUBJECTS: 977 women at 16-24 weeks gestation. MAIN OUTCOME MEASURES: Intrauterine death, birthweight, pregnancy-induced hypertension (PIH), antepartum haemorrhage. RESULTS: There was a 96.5% follow-up. Pregnancies with high AVRI values had a higher prevalence of proteinuric hypertension, placental abruption, small-for-gestational-age babies, and fetal loss. When AVRI was greater than 95th centile, the overall risk of pregnancy complications was 67%, and the risk of a severe complication was 25%. However, the sensitivity of the test for these complications was only 13% and 21% respectively. The risk for an individual woman with a high AVRI of developing a complication was increased by up to 9.8 times. CONCLUSION: Although Doppler screening does detect a unifying defect leading to perinatal death, pre eclampsia, growth retardation and placental abruption, the predictive values do not yet justify its introduction as a routine test. PMID- 1911606 TI - Thyrotrophin-releasing hormone--a lactation-promoting agent? AB - OBJECTIVE: To study the lactational and hormonal responses to nasal administration of thyrotrophin-releasing hormone (TRH) in puerperal women with inadequate lactation. DESIGN: Prospective randomized double-blind placebo controlled study. SUBJECTS: 19 puerperal women with inadequate lactation (less than 50% of normal milk yield) on the 5th day postpartum. INTERVENTIONS: 10 women were allocated to receive TRH administered by a nasal spray of 1 mg, four times daily, between suckling episodes, for 10 consecutive days starting on day 6 postpartum. Nine women were allocated to receive placebo sprays. MAIN OUTCOME MEASURES: Daily milk yield, serum levels of prolactin and thyroid hormones. RESULTS: Before treatment all the women had significant prolactin responses to TRH and suckling stimuli. At the end of 10 days of treatment, milk yield increased significantly in the TRH group from a mean of 142.0 (SD 33.9) to 253.0 (SD 105.3) g/day (P = 0.014). There was no significant change in the placebo group. Basal prolactin levels increased from a mean of 117.4 micrograms/l (SD 45.2) to 173.3 micrograms/l (SD 55.5) (P less than 0.001) in the TRH group whereas in the placebo group prolactin levels decreased from 137.2 (SD 69.5) to 82.0 (SD 37.7) micrograms/l. A further rise in prolactin levels and milk yield was seen in seven women in the TRH group who received a second 10-day course of TRH treatment at their own request. There was no significant change in levels of thyroid stimulating hormone, thyroxine and triiodothyronine during treatment in either of the two treatment groups and no signs of hyperthyroidism. CONCLUSION: Repeated nasal TRH administration between suckling episodes may improve defective lactation. PMID- 1911607 TI - The effect of maternal anaemia and iron deficiency on the ratio of fetal weight to placental weight. AB - OBJECTIVE: To examine the maternal influences which determine large placental weight and a high ratio of placental weight to birthweight. These are known predictors of adult blood pressure. DESIGN: Retrospective analysis of routine obstetric and haematology department records for a large cohort of pregnant women. SETTING: John Radcliffe Hospital, Oxford. SUBJECTS: 8684 pregnant women who were delivered between January 1987 and January 1989 and whose records could be linked to the results of two or more pregnancy blood counts. MAIN OUTCOME MEASURES: Placental weight and the ratio of placental weight to birthweight. RESULTS: Large placental weight was associated with a low maternal haemoglobin and a fall in maternal mean cell volume during pregnancy. The highest ratio of placental weight to birthweight occurred in the most anaemic women with the largest falls in mean cell volume. Large placental weight and a high ratio of placental weight to birthweight were also independently associated with a high maternal body mass index. Maternal smoking reduced placental weight, but increased the ratio of placental weight to birthweight. CONCLUSIONS: Anaemia and iron deficiency during pregnancy are associated with large placental weight and a high ratio of placental weight to birthweight. This points to maternal nutritional deficiency as a cause for discordance between placental and fetal growth. This may have important implications for the prevention of adult hypertension, which appears to have its origin in fetal life. PMID- 1911609 TI - Mode of delivery and neonatal death in 17,587 infants presenting by the breech. AB - OBJECTIVE: To study the effects of caesarean section on neonatal mortality in infants presenting by the breech. DESIGN: Population-based non-experimental comparison of infants presenting by the breech born vaginally with those born by caesarean section. Neonatal mortality rates were calculated for 250 g birthweight intervals. Weight-specific relative risks (RRs) were further adjusted for birthweight in 50 g categories. SETTING: New York City, 1978-1983. Data came from the Department of Health's computerized vital records on livebirths and infant deaths. SUBJECTS: 17,587 singleton breech livebirths greater than or equal to 500 g birthweight, with congenital anomaly deaths excluded. 6178 were born vaginally and 11409 were born by caesarean section. MAIN OUTCOME MEASURES: Birthweight specific and birthweight-adjusted neonatal mortality. RESULTS: At birthweights of 501 to 1750 g, the risk of neonatal death for breech infants born vaginally was significantly higher than the risk for those born by caesarean section (weight adjusted RR = 1.7). For breech infants with birthweights over 3000 g, the weight adjusted risk was 5.6 times greater for a vaginal birth compared with caesarean section. The addition of 16 additional control variables in multiple logistic regression analyses did not change these RRs. CONCLUSION: Population-based studies indicate that an increase in the caesarean section rate among breech singletons may be associated with increased neonatal survival, but a large multicentre randomized trial of management of breech presentation would answer the question much more definitively. PMID- 1911608 TI - Fetal blood sampling and pregnancy loss in relation to indication. AB - OBJECTIVE: To assess the relation between the indication for fetal blood sampling and pregnancy loss following the procedure. DESIGN: Retrospective study. SETTING: The tertiary referral Fetal Medicine Units at Guy's and University College Hospitals, London. SUBJECTS: Women undergoing diagnostic fetal blood sampling in four groups: (1) 94 having prenatal diagnosis with normal ultrasound findings; (2) 94 with a structural fetal abnormality; (3) 30 having fetal assessment and (4) 35 with non-immune hydrops. INTERVENTIONS: Freehand ultrasound guided fetal blood sampling from umbilical cord, intrahepatic vein or fetal heart. MAIN OUTCOME MEASURES: Pregnancy losses were divided into those within 2 weeks and those 2 weeks after the procedure, obstetric accidents and neonatal deaths. RESULTS: The 253 patients had fetal blood sampled on 268 occasions. Fifty-one pregnancies were terminated. Overall, 51 of the remaining 202 desired continuing pregnancies were lost, of which 19 (9%) were lost within 2 weeks of the procedure. After exclusion of the pregnancies that were terminated, the procedure related losses within 2 weeks of sampling were 1 in 76 (1%), 5 in 76 (7%), 4 in 29 (14%) and 9 in 36 (25%) in groups 1, 2, 3 and 4 respectively. CONCLUSIONS: The risk of fetal blood sampling is increased in abnormal pregnancies, reflecting the underlying pathology and this must be taken into account when counselling patients before the procedure. PMID- 1911610 TI - Haemorrhagic problems in obstetrics and gynaecology in patients with congenital coagulopathies. AB - OBJECTIVE: To review the obstetric and gynaecological problems in women with congenital coagulopathies. DESIGN: Retrospective review. SETTING: Regional Adult Haemophilia Unit, Glasgow Royal Infirmary. SUBJECTS: All women in contact with the Unit over a period of 30 years, comprising eight with von Willebrand's disease, 18 obligate carriers of haemophilia A and five obligate carriers of Christmas disease. Each woman was interviewed and details of their obstetric and gynaecological histories were obtained and their case records were reviewed. MAIN OUTCOME MEASURES: Haemostatic changes associated with pregnancy and gynaecological problems. RESULTS: In 14 pregnancies in seven patients with von Willebrand's disease, there were four primary and four secondary post-partum haemorrhages and a large perineal haematoma complicating an episiotomy. These problems arose despite the endogenous rise in factor VIIIc seen with pregnancy. All women seen with von Willebrand's disease complained of menorrhagia and had been referred to gynaecologists. Treatment included danazol, tranexamic acid and the contraceptive pill. Diagnostic curettage resulted in severe haemorrhage in one woman and two women with pelvic pain and dyspareunia were found to have spontaneous broad ligament haematomas, one requiring surgery. In 43 pregnancies in obligate carriers of haemophilia A and Christmas disease there were five post partum haemorrhages and a large perineal haematoma. CONCLUSION: In von Willebrand's disease it should be noted that adequate laboratory correction of factor VIIIc levels does not ensure clinical haemostasis; hence platelet function should also be measured. Patients with congenital coagulopathies pose particular problems for the obstetrician and gynaecologist and should be managed in close association with the local haemophilia centre. PMID- 1911612 TI - Immunocytochemical localization of neutrophil elastase in term placenta decidua and myometrium in pregnancy-induced hypertension. AB - OBJECTIVE: The aim of the study was to determine whether there was evidence of elastase containing neutrophils at the materno-fetal interface in women with pregnancy-induced hypertension (PIH). DESIGN: An observational prospective study. SETTING: The Simpson Memorial Maternal Pavilion Edinburgh. METHODS: Placentas were obtained at vaginal or abdominal delivery from 51 consecutive women, 23 had normal pregnancies (13 caesarean sections) and 28 had PIH (18 caesarean sections). An immunocytochemical technique was used to localize elastase containing neutrophils in the placenta, decidua and myometrium. MAIN OUTCOME MEASURES: The numbers of positively stained cells, estimated subjectively as minimal, moderate or heavy, in subchorionic plate, perivillous fibrin and decidua. RESULTS: In both normal and PIH pregnancies neutrophils were absent from the myometrium. However, elastase containing neutrophils were located in areas of fibrin in the subchorionic plate and around the villi although there was no significant difference between the normal and PIH group. Neutrophils were also located in the fibrin of the decidua and in this case the number was significantly greater in the PIH group than in the normal group and correlated with plasma urate. CONCLUSION: The release of neutrophil elastase in the decidua could contribute to the vascular damage evident in PIH. PMID- 1911611 TI - Magnesium intake and status and pregnancy outcome in a Danish population. AB - OBJECTIVE: To investigate the relation between pregnancy outcome and magnesium intake and status. DESIGN: A prospective observational study in which the estimate of nutrient intake and serum samples were obtained before the final outcome of pregnancy was known. A second part of the investigation was a cross sectional comparison of magnesium status of normal pregnant women and women with certain pathological pregnancies. SETTING: Antenatal clinic associated to the University Clinic of Obstetrics and Gynaecology, University of Aarhus, Denmark. SUBJECTS: 1203 consecutive women in the 30th week gestation were invited to participate in the study, 991 (82.4%) accepted and records for 965 (80.2%) were available for analysis. DATA: Food intake data were collected by a combination of a self administered questionnaire and a structured interview of a dietary history type. Serum samples were obtained from blood withdrawn in the 30th and 37th week gestation. Obstetric data were collected from the midwifery and hospital records. For a second part of the investigation, biopsies from the uterus and the abdominal rectus muscle were obtained from women delivered by caesarean section. RESULTS: In the women with normal pregnancies and in the three groups of pathological pregnancies (pre-eclampsia, SGA-infants and preterm labour) the average magnesium intake was within the range of 200 to 208 mg per 1000 kcal per day (SD 32) and there were no differences between the groups. Neither were differences in serum magnesium observed. Birthweight for gestational age was not influenced by magnesium intake. No differences in magnesium status as assessed by determination of magnesium content in muscle biopsies were found between the normal pregnancies and women with pre-eclampsia, SGA-infants or preterm labour. CONCLUSION: The intake of magnesium seemed adequate, and pre-eclampsia, SGA infants, or preterm labour did not seem associated with a low dietary intake of magnesium or magnesium deficiency. Routine magnesium supplementation during pregnancy is not recommended for populations of relative good socio-economic status. PMID- 1911613 TI - Unfavourable pregnancy outcome associated with congenital protein C deficiency. Case reports. PMID- 1911614 TI - Fetal middle cerebral artery flow velocity waveforms--a terminal pattern. Case report. PMID- 1911615 TI - The endometrial status of women on long-term continuous combined hormone replacement therapy. PMID- 1911616 TI - Human immunodeficiency virus type 1 (HIV-1) seroconversion during pregnancy does not increase the risk of perinatal transmission. PMID- 1911617 TI - Anti-Kell in pregnancy. PMID- 1911618 TI - Anti-Kell in pregnancy. PMID- 1911619 TI - Obstetric accidents: the patient's perspective. PMID- 1911620 TI - The crown-rump length in early human pregnancy: a reappraisal. PMID- 1911621 TI - Idiopathic thrombocytopenic purpura in pregnancy: a randomized trial on the effect of antenatal low dose corticosteroids on neonatal platelet count. PMID- 1911622 TI - Patient selection for hysteroscopic endometrial resection. PMID- 1911623 TI - Single step purification of potent antigenic protein from sparganum by gelatin affinity chromatography. AB - Out of many component proteins in crude saline extract of Spirometra mansoni plerocercoid (sparganum), 36 kDa and 29 kDa proteins were found to be the most antigenic and were already purified by immunoaffinity chromatography using monoclonal antibody as a ligand. In this study, a single step purification of these potent antigenic proteins of sparganum extract was investigated. When the crude saline extract was charged to gelatin-Sepharose 4B affinity column, 36 kDa and 29 kDa protein fractions were bound. SDS-polyacrylamide gel electrophoresis (PAGE) and SDS-PAGE/immunoblot confirmed that the bound protein to gelatin was serologically pure. When evaluated by ELISA with patients sera, the purified protein of 36 and 29 kDa also showed improved antigenicity. PMID- 1911624 TI - Immunohistochemical study on the antigenicity of each organ structure of Clonorchis sinensis. AB - An immunohistochemical study was performed to demonstrate comparative antigenicity of each body structure of the liver fluke, Clonorchis sinensis, such as the digestive tract, reproductive organs, excretory system, tegument and suckers. Indirect immunoperoxidase technique was applied, using formalin-fixed and paraffin-embedded sections of C. sinensis as the antigen. Pooled cat sera obtained 10 weeks after an experimental infection with C. sinensis and peroxidase conjugated goat anti-cat IgG were used as the primary and secondary antibodies, respectively. The intensity of immunohistochemical stain was very sensitive upon the titers of the primary and secondary antibodies, and their optimum dilutions were found to be 1:1,000-1:2,000 and 1:1,000, respectively. The intestinal epithelial cells, intestinal content and excretory bladder showed strong positive coloring reactions even at lower titer (1:2,000) of the primary antibody, whereas the uterine wall and eggs, vitelline glands, and male reproductive organs showed only weak positive reactions despite an increase in the antibody titer (1:1,000). On the other hand, the suckers, tegument, subtegumental cells and other parenchyma portions did not reveal any positive immunoperoxidase reaction at the same antibody titers. From the above results, it is highly suggested that the most potent antigenicity of C. sinensis occur from their excretory-secretory substances originated from the digestive and excretory organs. PMID- 1911626 TI - [Antibody-dependent rat macrophage-mediated damage to the excysted metacercariae of Paragonimus westermani in vitro]. AB - An in vitro immune effector mechanism against the target excysted metacercariae of Paragonimus westermani was demonstrated in the rat system. Peritoneal exudate cells, mainly macrophages from normal rats, showed adherence to and killing of excysted metacercariae of P. westermani in the presence of complement-independent serum from rats infected with Paragonimus metacercariae. These reactions were specific for the excysted metacercariae, as tissue-migrating juvenile worms were not affected. Damage of excysted metacercariae of P. westermani due to antibody and macrophages was assessed by morphological observation, by cell adherence reaction and by the use of vital dyes. Trypan blue dye exclusion proved to be a reliable indicator of judging metacercarial viability. Electron microscopic studies demonstrated that macrophages reacted with fuzzy material on the tegumental surface and fine structures in the syncytium of the parasites. The tubular tunnels formed between the basement membrane and muscle layers of the damaged parasites were also noticeable. The relevance of these findings to cellular immunity in the early paragonimiasis was discussed. PMID- 1911625 TI - [Antigenic localities in the tissues of the young adult worm of Paragonimus westermani using immunogold labeling method]. AB - In order to observe the antigenic localization in the tissues of the young adult Paragonimus westermani, immunogold labeling method was applied using serum immunoglobulins(IgG) of the dog which infected with isolated metacercariae from Cambaroides similis. The sectioned worm tissue was embedded in Lowicryl HM 20 medium and stained with infected serum IgG and protein A gold complex (particle size; 12 nm). It was observed by electron microscopy at each tissues of the worm. The gold particles were not observed on the basal lamina of the tegument, interstitial matrix of the parenchyma, the muscle tissue and mitochondria of the tegument. The gold particles were specifically labeled in the secretory granules in the vitelline cells. They were predominantly labeling on the epithelial lamela and lumen of caecum. The above finding showed that antigenic materials in young adult worm tissue were specifically concentrated on the tegumental syncytium as well as cytoplasm of tegumental cells. PMID- 1911627 TI - [A numerical taxonomic study on heterophyid trematodes]. AB - A numerical taxonomy was studied on a group of heterophyid trematodes and analysis was made on the following species: Metagonimus yokogawai (3 OTU, Operational Taxonomic Unit), Metagonimus Miyata Type (3 OTU), Metagonimus takahashii (2 OTU), Heterophyes dispar (2 OTU), Heterophyes heterophyes (1 OTU), Heterophyes nocens (2 OTU), Heterophyopsis continua (1 OTU), Pygidiopsis summa (3 OTU), Stellantchasmus falcatus (2 OTU) and Stictodora lari (2 OTU). Twenty-six morphological characters were measured and their values were expressed as relative ratios. Similarity and correlation matrix among each individuals were calculated. Clustering analysis by Ward's method and factor analysis were performed using the SAS (Statistical Analysis System) package. As a result, the groups belonging to the genus of Metagonimus were divided into three phenons (Metagonimus yokogawai, Metagonimus Miyata Type, M. takahashii), and Metagonimus Miyata Type was classified as the level of subspecies of M. takahashii. The groups belonging to the genus Heterophyes were clearly divided into three phenons (Heterophyes dispar, H. heterophyes, H. nocens), and H. nocens was classified as not a subspecies level of H. heterophyes but a distinct species. Other species were classified as distinct phenons. From these results, the application of numerical taxonomy on trematode classification is considered to be a great aid to determine the limit of taxa. PMID- 1911628 TI - Determination of the vector species of tsutsugamushi disease in Korea. AB - In order to determine the vector species of tsutsugamushi disease in Korea, chiggers were individually dissected, and internal contents were tested for Rickettsia tsutsugamushi organisms by means of indirect FA test, and each exoskeleton was mounted on slide for identification. Among 4,142 chiggers collected from 48 Apodemus agrarius at nine different localities during the period of July-November, 1989, 990 chiggers of 10 species of Trombiculidae were dissected and tested. Rickettsiae were confirmed in two Leptotrombidium pallidum larvae out of 447 tested, giving 0.4% of the infection rate. The chiggers of the other species tested were found negative. PMID- 1911629 TI - Activities of brush border membrane bound enzymes of the small intestine in Metagonimus yokogawai infection in mice. AB - The present study intended to evaluate the influences of Metagonimus yokogawai on the activities of brush border membrane bound enzymes of the small intestine. Mice were infected with 500 metacercariae respectively, and the worm recovery, morphological changes and enzyme activities were observed chronologically. A part of them were followed after the treatment. Recovered worms decreased in number continuously after the infection, and they were less than 10% after 2 weeks and almost zero after 28 weeks. Villous atrophy and stromal inflammation were found at two locations of the proximal jejunum from 2 weeks to 4 weeks after the infection. The enzymes, alkaline phosphatase, leucine aminopeptidase and disaccharidases (sucrase, lactase, maltase, and trehalase), showed lowered activities in the duodenum and proximal jejunum of the infected mice but they increased in the distal jejunum for the first two weeks. From three weeks after the infection, the activities were gradually recovered. In one week treated mice, they recovered the activities at 2 weeks from the treatment, but there found no differences of the activities between the 3 week treated group and infected controls. The present data reveal that M. yokogawai infection induces degenerative changes of the host's intestinal mucosa not only morphologically but functionally during the initial phase of infection. The lowered enzyme activities in acute metagonimiasis should be associated with malabsorption and diarrhea. PMID- 1911630 TI - A case of anisakiasis causing intestinal obstruction. AB - A 31-year old salesman living in Seoul developed suddenly abdominal pain due to intestinal obstruction. Exploratory laparotomy exhibited segmental jejunal cellulitis caused by penetrating Anisakis larva. The patient had eaten raw fish. The typical history of intestinal anisakiasis was presented with a short review of Korean patients of anisakiasis. PMID- 1911631 TI - Transmission of the normal and cataractous lenses. AB - Results of measurements of the transmission (total and in line) of cataractous lenses are presented. A magnitude is introduced which can be used as a measure of the in vitro opacity of lenses. PMID- 1911632 TI - Components of light scattered by eye lens. AB - Using the angular dependence of intensities of light scattered on sections of bovine lenses, we have determined correlation lengths related to the scattering samples. The correlations were calculated on the basis of random density and orientation fluctuation theory. The lenses were classified by means of an instrument for the measurement of transmission and the unscattered component of light. The correlation lengths are compared with dimensions of aggregates. PMID- 1911633 TI - NMR & fluorescence studies on human and animal lenses. AB - Our laboratory has demonstrated the potential of non-invasive biophysical methods in studying cataractogenesis. Initially these studies involved in vitro spectroscopic assays (UV, fluorescence and phosphorescence) on excised lenses or lens matter. In addition, we performed NMR pulse relaxation studies on extracted lenses which demonstrated an age-related increase in the T1 and T2 values of the normal lens. The in vitro fluorescence and NMR data suggested potential parameters for monitoring human and animal lenses in vivo. We then developed in vivo lens fluorescence densitography utilizing the Scheimpflug camera and have recently employed our Magnetic Resonance Imaging (MRI) method (using specially constructed small coils) to measure the moderately bound lens water compartment (T2) in vivo. Both of these in vivo methods correlate with our in vitro data and they demonstrate age-related changes in the normal lens; - i.e. - a progressive increase in fluorescence intensity and longer T2 values. Indices have been developed which permit us to detect abnormal lens fluorescence and changes in the moderately bound lens water (T2) compared with normal values for each specific age group by decade. These 2 non-invasive biophysical techniques can detect pre cataractous changes in the living clear lens, months to years before any type of opacity becomes manifest with the conventional slit lamp method. The MRI technique can be performed in less than 20 minutes and the lens fluorescence method requires 4-6 minutes; thus they provide a rapid and objective in vivo measure of the status of the living lens as well as a method for evaluating anti cataract drug efficacy. PMID- 1911634 TI - Progressive saturation relaxation spectroscopy. Investigations on lens nucleus and cortex at low temperature. AB - A systematic study of the temperature dependence of progressive saturation relaxation spectra was carried out on the nucleus and cortex of normal and cataractous eye lenses at different temperatures below freezing. A more complicated fine structure was detected, than was previously thought. The method utilized may well be applied in tomography as well. PMID- 1911635 TI - Study of NH stretching band in Raman spectra of animal lenses. AB - The contour of OH stretching bands is very sensitive to any intra or intermolecular interactions. Thus it is interesting as a "marker" of cataractous stage of eye lens. Relative peak intensity and depolarization ratio of NH stretching band overlapping OH contour were estimated. PMID- 1911636 TI - Some fluorescence properties of cataractous eye lenses. AB - The loss of transparency of the ocular lens is caused by the increase of light scattering as a result of structural changes and by the increased absorption of the visible light due to the accumulation of pigments. Following light absorption, these pigments undergo non-radiative and radiative (luminescence) processes which can be monitored spectroscopically. The paper presents some new results concerning the excitation spectra, decay times and polarization of the lenticular fluorescence. Fluorophore heterogeneity manifests itself in all the experimental data. A striking behaviour of the emission anisotropy as a function of temperature is found, particularly for cortical cataract lenses, indicating temperature-induced structural changes at about 20 degrees C. PMID- 1911637 TI - IR spectra of lens crystallins. AB - The IR technique has been applied to investigate secondary structure of the crystallins from the normal bovine eye. Crystallins have been isolated by column chromatography. IR spectra were recorded for the solid phase of proteins. From these spectra, especially amide I, amide II and amide V bands, the presence of alpha-helix, beta-sheet, beta-chain and unordered structures is stated. It was elucidated that alpha-crystallins are present mainly in a beta-sheet conformation but they also contain a considerable quantity of alpha-helix and a slight quantity of unordered and beta-chain forms. In beta H-crystallins, alpha-helix and, in a lesser percentage, beta-structures predominante. beta-sheet, alpha helix and a low content of beta-chain forms are present in beta L-crystallins. In gamma-crystallins all forms secondary structure have been found, with predominance of beta-sheet and alpha-helix forms. A satisfactory agreement has been noticed between the forms of secondary structures in crystallins investigated by the IR technique and the results obtained by means of other methods. In conclusion IR spectroscopy has been suggested to be applied to observe crystallin structure during formation and development of a cataract. PMID- 1911638 TI - Structure/function relationship between optics and biochemistry of the lens. AB - The lens is an important element in the optical system of the eye. It has a gradient of refractive index for purposes of aberration control and in order to provide the ocular system with sufficient power. The lens also contains unique structural proteins. Although much work has been done to characterize the lens proteins, a structure/function relationship between these entities and the optics of the normal lens had not been previously considered. To investigate if such a relationship exists, biochemical and optical investigations were carried out under the common theme of development and aging. Investigations of distribution patterns of the three protein classes and measurements of the refractive index gradient were made on bovine and human lenses over wide age ranges. The results of these studies were compared. Although there was no direct evidence of a link between a single protein class and the index gradient, there are hints from interspecies comparison, that the level of LMW proteins may determine the magnitude of the refractive index. It is also possible that the insoluble fraction, which bears the greatest relationship in trend to the refractive index gradient, may represent proteins (largely pounds-crystallins) which have been structurally altered in situ in order for the lens to maintain viable optical function under the conditions of continual growth and aging. PMID- 1911639 TI - Post-translational modification of lens proteins in cataract. AB - Evidence supporting the role of non-enzymic post-translational modification of lens proteins in cataract is reported as presented at a meeting in Bydgoszcz, Poland in August 1990. Glycation and carbamylation have been studied intensively recently. Both produce modified proteins with properties similar to those of 'molten-globule' intermediates of protein folding and unfolding pathways. PMID- 1911640 TI - Reactive metabolite hypothesis for human senile cataract. AB - One of the research programs of the Australian Cataract Research Foundation (ACRF) is aimed at investigating the possibility that senile cataract both cortical and nuclear, may result from the interaction of reactive metabolites with proteins in the lens. In particular we are exploring the potential role of tryptophan metabolites for example, 3-hydroxyanthranilic acid, in this disease. This article examines briefly some aspects of this approach. PMID- 1911641 TI - Relationships between human cataracts and environmental radiant energy. Cataract formation, light scattering and fluorescence. AB - This preliminary report has two parts. The first is based upon data obtained from a group of cataract patients in southern Florida (USA) with the object of relating the types of cataracts removed to their personal background and their protein biochemistry. Intra-capsular cataract surgery patients at the Venice Eye Clinic (Florida) were interviewed, and their extracted lenses were classified. The parameters were: age, place of residency, occupation, medical and family history and indoor/outdoor activity. Subcapsular cataracts were found mainly in the youngest patients and in those who were in Florida the least. Mixed cataracts predominated in the oldest patients, while non-nuclear cataracts were associated most with outdoor activity. Water-insoluble protein was elevated in nuclei of lenses with nuclear opacities. Soluble proteins in the nuclei of nuclear cataracts had increased levels of voided (heavy) protein, beta-crystallins, and less than 20 Kd peptides. The above changes were enhanced in brunescent cataracts. In lenses with cortical opacities, only increased size heterogeneity in the beta-crystallin region was observed. The second part of this report is based upon direct measurements of the optical properties of freshly extracted intra-capsular cataracts obtained in Rochester, New York (USA). The purpose was to attempt to learn the relative contributions that absorption, scattering, and fluorescence make toward obscuring vision. A general conclusion is that the shorter wavelengths of radiant energy in environmental lighting influence the above-stated optical properties the most, and thus appear to be the major contributors to obscured vision. PMID- 1911642 TI - Histopathological studies of human lenses. AB - Histopathological findings in 33 intracapsularly removed lenses and 35 enucleated eye-balls are presented. Anterior and posterior subcapsular cataracts were mostly seen in traumatic and advanced senile cataracts. Characteristic features of the latter were cortical degeneration and liquefaction with formation of Morgagnian globules and nuclear sclerosis. Anterior lens epithelium had more tendency to undergo fibrous pseudometaplasia, while equatorial epithelium migrated posteriorly with "bladder cell" formation. In complicated and traumatic cataracts, apart from abnormal proliferation of lens epithelium, frequent synechiae with iris and/or cyclitic membranes were seen. Phacoanaphylactic uveitis was observed in 6 eyes with capsular defects. Pseudoexfoliative material was found in 5 cases. It is suggested, that domination of proliferative changes in traumatic and complicated cataracts, in contrast to senile cataracts, results from the availability of different mitogenic factors in injured and inflammed eyes and may be due to the younger age of patients in this group. PMID- 1911643 TI - Lens protein gene expression: alpha-crystallins and MIP. AB - The crystallin genes encode the major soluble proteins of the lens. Some of the crystallin genes are expressed exclusively in the lens while others are also expressed in different tissues. The two alpha-crystallin genes, alpha A and alpha B, differ in their tissue specificity. Transcription of the alpha A-crystallin gene occurs only in the lens, while the alpha B-crystallin gene is also expressed in other tissues, including heart, skeletal muscle, kidney, lung and brain. MIP (also called MP26), the major intrinsic protein of the lens fiber membranes, is also expressed exclusively in the lens. Correct expression of both alpha crystallin and MIP are required for normal lens function. Here we review our studies on the molecular basis of expression of the alpha-crystallin and MIP genes in the lens. The 5' flanking sequences containing the initiation site of transcription of the alpha A-crystallin, alpha B-crystallin and MIP genes were fused to the bacterial chloramphenicol acetyltransferase (CAT) gene, and the expression of this reporter gene was studied in transient assays and transgenic mice. DNA sequences flanking the 5' end of the alpha A-crystallin gene contain regulatory elements responsible for the lens-specific expression and developmental regulation of the CAT gene in transgenic mice. Interestingly, although some of the murine alpha A-crystallin regulatory sequences are conserved in the human and chicken genes, different functional regulatory elements appear to control the expression of the murine and chicken alpha A-crystallin genes. The 5' flanking sequence of the alpha B-crystallin gene preferentially directs expression of the CAT gene to the lens and to skeletal muscle. Different regulatory elements of the alpha B-crystallin gene appear to be responsible for its transcription in various tissues. The 5' flanking sequence of the MIP gene also contains regulatory elements that direct expression of the CAT gene to lens cells; these sequences are not functional in transfected non-lens cells and are different from the cis regulatory elements controlling alpha-crystallin gene expression. The multiplicity of cis-regulatory elements controlling the transcription of these three genes indicates the complexity of the mechanisms that regulate gene expression in the lens. PMID- 1911644 TI - Studies of aqueous humor proteins in rabbits after posterior chamber lens implantation. AB - In 13 rabbits, 1 month to 1 year after posterior chamber lens implantation/polymethylmetacrylate/, the level of aqueous humor proteins was evaluated and the proteins separation in polyacylamide gel was performed. The studies were also carried out in unoperated eyes of the same animals and control group was composed of the eyes before surgery. It was found that in pseudophakic eyes an increased level of proteins remained during the whole year/the highest one month after surgery, slowly decreasing afterwards/, with the appearance of additional fractions. The moderate increase of the proteins concentration was also observed in unoperated eyes. The increase of aqueous humor proteins in pseudophakic eyes indicates that the presence of polymethyl metacrylate is not completely indifferent to the eyeball in spite of the suggestions derived from the clinical observations. PMID- 1911645 TI - Lens coenzymes and cataract formation. AB - The present work discusses the role of certain coenzymes in the metabolic and the biophysical processes maintaining the nativity of lens components. It also analyses results of the levels of oxidized and reduced forms of nicotine amide coenzymes and glutathione in the lens folling insults by both physical and chemical cataractogenic agents. The role of flavine and flavine coenzymes in the maintainance of the biochemical and biophysical stability of the lens has also been discussed. Data concerning the enzymatic biosynthesis and degradation of the lens coenzymes has been presented. PMID- 1911646 TI - Light signals in leaf and chloroplast development: photoreceptors and downstream responses in search of a transduction pathway. AB - Light affects both the development and the metabolism of plants. In addition to the role of light in providing energy for photosynthesis, light signals cause profound changes in the morphology of the developing young seedling, including cotyledon expansion, leaf development, inhibition of stem growth, and production of chlorophyll in the photosynthetically competent chloroplast. The light dependent development of plants (photomorphogenesis) is a complex process resulting from the combined action of several photoreceptors. This review summarizes what is known of the red- and blue-light photoreceptors that regulate dicotyledonous seedling development and the complexity of the downstream responses. Special emphasis is placed on the recent progress made toward genetic and biochemical dissection of the signal transduction pathways. PMID- 1911647 TI - Developmental patterns in the expression of Myf5, MyoD, myogenin, and MRF4 during myogenesis. AB - By using the polymerase chain reaction to amplify specific regions of the respective cDNAs, we have studied the expression of genes encoding the myogenic regulatory factors Myf5, MyoD, Myogenin, and MRF4 (Myf6, herculin) in cultured mouse muscle cells (inducible and permissive C2 cells and Sol8 cells). These cell lines may represent distinct stages in the progression of determined, or committed, muscle cells toward terminal differentiation. Transcripts for Myf5 were detected at the myoblast stage in all the committed muscle cells tested. Expression of the gene for MyoD appeared to be optional at the myoblast stage (MyoD is present in permissive myoblasts and absent from inducible myoblasts) but, like Myogenin, was found to accompany terminal differentiation. Furthermore, forced expression of MyoD converted inducible C2 cells into permissive cells. Expression of MRF4 was found to follow expression of the three other factors and to occur after the onset of terminal differentiation. Of particular interest was the finding that expression of MRF4 was temporally correlated with expression of the gene for the acetylcholine receptor epsilon-subunit that is characteristic of the adult receptor. In vivo, the only transcripts for myogenic regulatory factors to be detected in 8-day mouse embryos were those for Myf5, while expression of MRF4 followed expression of Myf5, MyoD, and Myogenin in developing limbs. Temporal and phenotypic differences related to the expression of Myf5, MyoD, Myogenin, and MRF4 suggest that these factors fulfil distinct roles in the control of myogenesis. PMID- 1911648 TI - Modulation of the mitogenic activity of eukaryotic translation initiation factor 4E by protein kinase C. AB - Eukaryotic initiation factor-4E (eIF-4E) binds to the cap structure of eukaryotic mRNAs and is a component of the cap-binding protein complex eIF-4F. eIF-4E is present in cells in limiting concentrations and is phosphorylated both in vivo and in vitro by protein kinase C (PKC). Recently, eIF-4E has been implicated as an intracellular transducer of extracellular growth signals; microinjection of recombinant eIF-4E into quiescent NIH 3T3 cells induced DNA synthesis. In the present report, the mitogenic activity of eIF-4E was examined after coinjection with PKC. Recombinant eIF-4E was phosphorylated by PKC at the same amino acid that is phosphorylated in cultured cells and reticulocytes in response to phorbol ester. At limiting concentrations of eIF-4E, coinjection with PKC induced a fivefold increase in the mitogenic activity of eIF-4E. Injection of PKC alone or coinjection of eIF-4E with cAMP-dependent protein kinase (PKA) or the Raf protein had no effect. These results suggest that the mitogenic activity of eIF-4E is enhanced by PKC-specific phosphorylation and that phosphate addition is a rate limiting step in eIF-4E activity. PMID- 1911649 TI - Cell polarity: intrinsic or externally imposed? AB - A basic question in studies of the genesis of cell polarity is whether the polarity is an intrinsic and permanent property of cells or whether it is externally imposed by signals at the cell periphery. Current models favor the possibility that an external signal selectively imposes a polarized cell morphology. However, recent data from different experimental systems are discussed here that support the idea that an intrinsic polarity in animal cells is maintained through a dynamic process involving specific activities of the cortical microfilament system and the centrosome-microtubule complex. In this view, external signals capable of modulating cell polarity, for example, during chemotaxis or histogenesis, do so by acting on mechanisms that maintain cells permanently polarized. The contribution of the cytoskeleton to the genesis of cell polarity is discussed, with particular reference to experimental evidence for global cytoskeletal dynamics, and it is suggested that critical advances in our understanding of the maintenance of cell polarity will depend on our obtaining further knowledge of the molecular mechanisms controlling interactions between microtubules and microfilaments. Microtubules appear to exert an inhibitory control on the recruitment of cytoplasmic myosin into the cortex, and there are data indicating that the centrosome and centrioles could actively contribute to the establishment of cell polarity. PMID- 1911650 TI - Video laser ophthalmoscopy in diabetes. PMID- 1911651 TI - Retinal microcirculation in patients with diabetes mellitus: dynamic and morphological analysis of perifoveal capillary network. AB - The new scanning laser technique allows one to quantify the retinal microcirculation. A digital image analysing system was used to study capillary blood flow velocities and morphological parameters of perifoveal intercapillary areas and foveal avascular zones in normal and diabetic subjects. Diabetic patients showed a significant reduction in capillary blood cell velocities in comparison with normal subjects. Perifoveal intercapillary areas and foveal avascular zones were significantly increased in all stages of diabetic retinopathy, and both parameters increased with progressing diabetic retinopathy. Significant changes in the perifoveal intercapillary areas were observed between normal subjects and patients with no retinopathy. PMID- 1911652 TI - Ocular manifestations in fetal alcohol syndrome. AB - Eight children with the fetal alcohol syndrome are described with ocular anomalies. They all had a strong history of maternal alcohol abuse throughout pregnancy, especially in the first trimester. All the children had eye abnormalities. These included external eye lesions, Peters' anomaly, lens opacification, ocular motility disorders, and optic nerve hypoplasia. PMID- 1911653 TI - Regressed retinopathy of prematurity and its sequelae in children aged 5-10 years. AB - Regressed retinopathy of prematurity (ROP) and its sequelae were studied in children born prematurely (less than 1501 g birth weight and/or less than 33 weeks gestational age) in Stockholm county during 1976-81. Through various searches of the records at the different eye departments and other sources in Stockholm county we found that 134 out of a total of 528 premature babies (25.4%) had needed ophthalmic care for different reasons. They were re-examined and reliable information on the fundus could be obtained for 105 of them. The frequency of regressed ROP was 45.5%. Severe forms with vitreoretinal scarring and retinal traction were seen in 9.7% of cases and moderate forms with pigmentary changes and/or vitreoretinal interphase changes in 35.8%. The sequelae of regressed ROP were mainly reduction of visual acuity and myopia. Children with a birth weight below 1000 g and a gestational age less than 30 weeks presented the highest rate of regressed ROP (68.5% and 61.9%) and ocular abnormalities. PMID- 1911654 TI - Evaluation of bilirubin as possible protective factor in the prevention of retinopathy of prematurity. AB - Retinopathy of prematurity (ROP) appears to be a multifactorial disease, the prevention of which is probably impossible even with the most accurate methods of blood-gas monitoring and oxygen restrictions. The oxidative processes and consequent formation of free radicals are probably influenced by the availability of various antioxidants in the immature retina. Bilirubin, the end product of haem catabolism, has recently been regarded as a potential physiological antioxidant. In order to test the suggestion as to the possible effect of bilirubin in reducing the incidence of ROP a retrospective study was undertaken of the medical records of 151 neonates born between 1984 to 1988 who weighed less than 1500 g. Of these, 78 had various degrees of ROP, whereas 73 had no ROP and served as a control group. The daily mean bilirubin values were analysed in accordance with gestational age and birth weight as well as the severity of ROP, and the results were compared with those obtained for the control group. The results showed no correlation between bilirubin levels and severity of ROP in all subgroups of gestational age and birth weight. These findings indicate that there is no apparent protective effect of bilirubin on the development of ROP. PMID- 1911655 TI - Supplemental gas tamponade after conventional scleral buckling surgery--a simple alternative to surgical revision. AB - Supplemental intravitreal gas injection was used in the early postoperative period in an attempt to achieve long term retinal reattachment in 11 cases of failed scleral buckling surgery. Success was dependent on the presence of a correctly placed scleral buckle underlying all breaks. Surgical revision was thereby avoided in these patients. However, when the scleral buckle was inadequate the technique failed. PMID- 1911656 TI - Reappraisal of the ratio of disc to macula/disc diameter in optic nerve hypoplasia. AB - The ratio of disc to macula/disc diameter is characteristically increased in eyes with optic nerve hypoplasia. We present the largest reported series of patients with a definitive diagnosis of optic nerve hypoplasia for whom this ratio has been determined. All measurements were made by an independent masked observer. Our results are in accordance with previous reports. A ratio of 2.94 provides a one-tailed upper population limit of 95%. An attempt has been made to correlate optic disc size and visual acuity. In 75% of bilateral cases the eye with the relatively smaller optic disc was found to have a better Snellen visual acuity than the fellow eye. This suggests that additional pathogenic mechanism(s) may have determined the eventual visual outcome in such eyes. Such mechanisms include macular hypoplasia, high refractive error, refractive amblyopia, central scotoma, and optic atrophy. PMID- 1911657 TI - Double-masked trial of topical acyclovir and steroids in the treatment of herpes zoster ocular inflammation. AB - Ninety seven new patients with ophthalmic zoster were randomly allocated to three topical treatment groups: acyclovir (ACV) ointment and placebo drops (AP), placebo ointment with steroid drops (PS), and acyclovir ointment with steroid drops (AS). The dosage administered was determined by the score of the ocular inflammation. Follow-up was for at least one year. The results showed that topical ACV alone is insufficient for severe ocular inflammation but is not inclined to lead to recurrences in milder cases. Topical steroid alone is effective but tends to necessitate prolonged treatment. Combined steroid and ACV is questionably better than steroid alone and causes marginally fewer rebound inflammations. PMID- 1911658 TI - Progression of diabetic retinopathy after cataract extraction. AB - The course of diabetic retinopathy following cataract extraction was studied retrospectively in 89 patients (89 eyes). Cataract extraction was extracapsular in 12 eyes (13.5%), extracapsular with intraocular lens implantation in 37 (41.6%), and intracapsular in 40 (45%). In 55 eyes (61.8%) there was no change in the retinal status after surgery, and in 34 (38.2%) there was progression of diabetic retinopathy. In the eyes showing progression there was appearance or aggravation of non-proliferative changes in 85.3% and development of proliferative diabetic retinopathy in 14.7%. Most of these eyes (91%) deteriorated within six months of surgery. Risk factors for the progression of diabetic retinopathy were the preoperative existence of diabetic retinopathy (p less than 0.005) and the need for antidiabetic agents in addition to dietary control in the management of diabetes (p less than 0.025). PMID- 1911659 TI - Alterations in elastin of the optic nerve head in human and experimental glaucoma. AB - The optic nerve heads from normal and glaucomatous eyes of humans and monkeys were examined by light and electron microscopy for the presence and distribution of elastin. Elastin densely lined the insertion of the lamina cribrosa into the sclera and was prominent in the laminar beams. The long axis of elastin paralleled that of the collagen fibrils and corresponded to the directions of expected forces on the tissue. In glaucomatous eyes elastin molecules were curled instead of straight and seemed disconnected from the other elements of the connective tissue matrix. Laminar beams stretch and reorganise their substructure during glaucomatous atrophy, probably leading to changed compliance. Differences in elastin function may have a part in susceptibility to glaucomatous injury. PMID- 1911660 TI - Association of Vistech contrast sensitivity and visual field findings in glaucoma. AB - Single eye visual fields and contrast sensitivity were assessed in 60 subjects, who were being followed up in a glaucoma clinic for manifest glaucoma or a suspicion of glaucoma because of raised intraocular pressure. The Fieldmaster 5000 (static/kinetic perimeter) was used for the visual fields, and a Vistech wall chart sine wave grating test was used for contrast sensitivity measurements. The subjects were divided into three groups--defect (D), suspect (S) and normal (N)--on the basis of their perimetric findings by subjective grading of 16 perimetric scoring categories for each visual field. The mean Vistech sensitivity levels were not found to be significantly different between the D, S, and N field subgroups at any of the five spatial frequencies provided on the test charts (1.5, 3, 6, 12, and 18 cycles per degree). Complex algorithms combining results from two or more spatial frequencies also failed to yield any significant differences between the groups. Diagnostic sensitivity and specificities relating Vistech contrast sensitivity findings to groups N and D never concomitantly exceeded 60%. PMID- 1911661 TI - In-toto removal of a subretinal Cysticercus cellulosae by pars plana vitrectomy. AB - A case of subretinal cysticercosis was treated with laser coagulations round the cyst prior to surgery. In-toto removal of the living cysticercus was performed by pars plana vitrectomy. Two weeks after surgery 25/20 vision was regained. Histopathology of the cyst confirmed the clinical diagnosis. PMID- 1911662 TI - Spontaneous passage of a dacryolith. AB - A patient had four episodes of recurrent dacryolith over 14 years. Each attack of acutely painful dacryocystitis was terminated by spontaneous passage of the dacryolith. Biochemical and dacryocystographic evidence help to explain the pathogenesis of the condition. PMID- 1911663 TI - Candida tropicalis endophthalmitis following penetrating keratoplasty. AB - A case of Candida tropicalis endophthalmitis following penetrating keratoplasty is presented. The donor was an alcoholic, who died of bronchopneumonia and pancreatitis. We presume the candida infection was transmitted by the donor because Candida tropicalis was cultured in life from the donor's throat swab and corresponding fungal elements were discovered post mortem in kidney sections of the donor. PMID- 1911664 TI - Retinal vasculitis in a mother and her son with human T-lymphotropic virus type 1 associated myelopathy. AB - A 53-year-old woman had difficulty in walking, raised titres to human T lymphotropic virus type 1 (HTLV-1) in serum and cerebrospinal fluid, and yellowish white retinal lesions and vasculitis in the right eye. Her 20-year-old son also had difficulty in walking, raised titres to HTLV-1 in serum and cerebrospinal fluid, and retinal vasculitis and multiple whitish vitreoretinal spots in both eyes. PMID- 1911665 TI - Orbital squamous cell carcinoma after retinal detachment surgery. AB - We report on a 76-year-old patient with a squamous cell carcinoma of the left orbit. The tumour had no connection with the conjunctiva but was located at the site of an encircling band which had been inserted 13 years before. A major part of the tumour presented as a well circumscribed solid mass within the extraocular tissues next to the inferior equator, but the exenteration specimen also showed tumour extension within the adjacent choroid. Histological examination showed a well differentiated keratinising squamous cell carcinoma with numerous mitotic figures and many epithelial pearls. A thorough examination in search of a primary carcinoma of the lacrimal gland or the sinus, with invasion into the orbit, or an epithelial neoplasm elsewhere suggestive of metastatic disease into the choroid did not reveal any specific pathological findings. Thus the most probable origin of the tumour seems to be epithelium which had been misplaced during retinal detachment surgery and had subsequently undergone malignant transformation. PMID- 1911667 TI - Broken egg shells of acarine origin on the eyelid margin. PMID- 1911666 TI - Delayed ciliochoroidal detachment following intraocular lens implantation. AB - Three patients who had extracapsular cataract extractions with intraocular lens implants developed delayed ciliochoroidal detachments, which responded to systemic steroid therapy. This rare complication may have been due to ciliary sulcus fixation of the implant. The possible mechanism and treatment are discussed. PMID- 1911668 TI - The ocular pulse. PMID- 1911669 TI - Fine needle cutting biopsy of lesions of the head and neck. AB - One hundred and twenty-four fine needle cutting biopsies of lesions of the head and neck have been carried out over the last 7 years. While the overall accuracy of diagnosis was 79%, the accuracy of the 43 biopsies carried out during the last 2 years was 93%. These results compare very favourably with published results of the accuracy of fine needle aspiration cytology. PMID- 1911670 TI - Evaluation of various treatments for carcinoma of the mandibular region. AB - Cancers of the mandibular region show the lowest survival rates of all oral cancers. In order to compare the effect of five different modes of treatment (including surgery and/or radiotherapy), a series of 159 patients was analysed. When adjustments were made for age, sex and tumour stage in a log-linear multivariate analysis, no differences between treatments in the 5-year relative survival rates (RSR) could be demonstrated for stage I and II tumours. In stage III and IV tumours, radiation treatment alone resulted in poor survival. Between the other four treatments, all including surgery, no statistically significant differences in the 5-year relative survival rates were found. Radiation therapy as an element in combination therapy may have postponed a recurrence but did not affect the 5-year survival rate. For advanced tumours, mostly responsible for the low overall 5-year RSR, higher survival rates can possibly be achieved by improving surgical treatment of the primary lesion and the neck. At present, however, only earlier diagnosis might significantly increase the survival rates. PMID- 1911671 TI - Complications of pharyngostomy. AB - An account is given of a fatal complication following the use of a pharyngostomy feeding tube. The literature on this topic is reviewed with regard to complications. Of the 671 patients that have been reported previously there have been no fatal or serious complications and minor complications were reported in only 42 patients. We regard the technique of pharyngostomy to be safe but recommendations are made to avoid the complication reported here. PMID- 1911672 TI - The effects of positioning variations in transcranial radiographs of the temporomandibular joint: a laboratory study. AB - The relationship of the mandibular condyle to the articular fossa and eminence as seen on transcranial oblique lateral (TOL) radiographs of the temporomandibular joint is used by some clinicians as an important diagnostic sign and indicator of treatment. The literature is divided on the validity of this. The aim of this study was to consider the effects of variations in both the position of the joint and the X-ray beam orientation on the image seen on TOL radiographs. TOL radiography of a mounted block specimen of a human temporomandibular joint and associated tissues was carried out using a range of specimen rotations (+20 degrees to -20 degrees with respect to the sagittal plane) and X-ray beam angulations (20 degrees, 25 degrees, 30 degrees). Analysis of tracings of the joint images showed that most of the parameters measured varied by statistically significant amounts with changes in either specimen rotation or beam angulation. It is concluded that any convention which purports to evaluate the position of the mandibular condyle in relation to the articular fossa from TOL radiographs is invalid when the orientation of the condyle to coronal and horizontal planes is unknown. PMID- 1911673 TI - Trends in the aetiology of maxillofacial fractures in the United Kingdom (1977 1987). AB - A survey was undertaken to assess changes in the aetiology of maxillofacial fractures in the United Kingdom between 1977 and 1987, using data which had been collected in British departments of Oral and Maxillofacial Surgery. Data were available from units serving 17 million people and included details of patients from a broad spread of rural and urban areas. Analysis of data from the 27 maxillofacial units able to supply details from both 1977 and 1987 showed an overall increase of 20% in numbers of patients with maxillofacial fractures, though a trend towards fewer severe injuries was also a feature over the same period. Numbers of patients injured in road accidents had decreased by 34%, numbers of patients injured in assaults had increased by 47% whilst numbers of patients injured in all other ways had increased by 39%. PMID- 1911674 TI - An unusual Le Fort II fracture. PMID- 1911676 TI - The biochemical and haemodynamic effects of adrenaline in lignocaine local anaesthetic solutions in patients having third molar surgery under general anaesthesia. AB - The effects of adrenaline-containing and adrenaline-free lignocaine local anaesthetic solutions injected in doses consistent with clinical practice on plasma potassium concentration, blood glucose levels and haemodynamic responses were investigated in 20 patients having third molar surgery under general anaesthesia. All patients received a standard general anaesthetic regime. Ten patients were given 4.0 ml of 2% lignocaine as an inferior dental and long buccal block during their general anaesthetic and the other 10 received 4.0 ml of 2% lignocaine containing 1:80000 adrenaline in the same manner. There were no significant differences between treatments in blood pressure or heart rate. However, there were significant differences between treatments in plasma potassium concentration and blood glucose levels. PMID- 1911677 TI - Senior registrars' views on training in oral and maxillofacial surgery. AB - Fifty-three British senior registrars in oral and maxillofacial surgery (OMS) were sent a questionnaire designed to determine their views on some of the main aspects of training in the specialty. Thirty-seven returns were received (70%), 36 completed. This paper reports and discusses the results of the survey. PMID- 1911675 TI - Assessing the eruption of lower third molars on the basis of radiographic features. AB - To determine radiographic features by which one could estimate whether lower third molars are likely to erupt after the age of 20 years, university students with a total of 84 unerupted or partially erupted lower third molars were followed up. Five radiographic features of each third molar were measured from the panoramic tomogram taken at age 20 years, and the status of third molars was examined for a second time at age 26 years. The results showed that the lower third molars that did erupt after the age of 20 years were initially: 1) root formation complete; 2) impacted in soft tissue; 3) vertical; 4) placed at the same occlusal level as the neighbouring second molar; 5) showed sufficient space between the ramus and the second molar. In contrast, the teeth that remained impacted at the age of 26 years showed such initial features as: 1) incomplete root formation; 2) embedding in bone; 3) mesioangularity; 4) situated at the cervical level of the neighbouring second molar. It was concluded that a panoramic tomogram taken at age 20 years revealed radiographic features on which an estimation of future eruption of mandibular third molars could be based. PMID- 1911678 TI - Plasma-cell tumours of the condyle. AB - Plasma cell tumours are a group of disorders which are characterized by neoplastic proliferation of atypical plasma cells involved in the production of monoclonal immunoglobulins. Bone pain, renal insufficiency and normocytic normochromic anaemia are suggestive data for diagnosis. In 12-15% of cases of multiple myeloma, the first manifestation of the disease appears in the jaw bones and oral cavity. Two cases of multiple myeloma affecting the mandibular condyle are presented, and the incidence of oral and maxillofacial lesions is briefly reviewed. PMID- 1911679 TI - Solitary infantile myofibromatosis. AB - Infantile myofibromatosis is an uncommon, benign, probably hamartomatous proliferation of myofibroblasts. Its growth is typically self-limiting but histologically it can simulate a sarcoma. A rare case of solitary infantile myofibromatosis presenting as an intraoral mass in a 10-year-old girl is reported. PMID- 1911680 TI - The median cleft face syndrome with associated cleft mandible, bifid odontoid peg and agenesis of the anterior arch of atlas. AB - A case is reported of median cleft face syndrome with bifid tongue and odontoid peg and failure of formation of the anterior arch of the atlas. These are features which have not been reported previously. The preoperative CT demonstrated its potential to enhance our understanding of complex and rare craniofacial deformities. PMID- 1911681 TI - Fabrication of custom made tissue spacers for use in tissue augmentation. PMID- 1911682 TI - Pegs for inferior repositioning of the maxilla. PMID- 1911684 TI - Surgery in the Third World. PMID- 1911683 TI - Cryotherapy for trigeminal neuralgia. PMID- 1911685 TI - Temporalis muscle donor site. PMID- 1911686 TI - Delayed miniplate osteosynthesis for mandibular fractures. PMID- 1911687 TI - Reliability of cephalometric analysis using manual and interactive computer methods. AB - This study compares the results of cephalometric analyses using manual and interactive computer graphics methods. Results are statistically in favour of the interactive computer system. This study provides a basis for ongoing research into alternative methods of cephalometric analyses, such as digitization and automatic landmark identification using sophisticated computer vision systems. PMID- 1911688 TI - Self-esteem and aesthetics. AB - Self-esteem/self-concept and aesthetics were measured in three groups. One group prior to orthodontic treatment, one group following completion of active orthodontic treatment and an untreated group. Improvement in dental and/or facial aesthetics does not necessarily lead to an increase in self esteem. PMID- 1911689 TI - The effect of beam collimation in lateral radiographic cephalometry. AB - A study was carried out to compare the image contrast of lateral cephalometric radiographs taken with and without the modified beam collimation and to evaluate the effect of this on the reliability of cephalometric measurements. The findings indicated that the cephalographs taken with modified beam collimation consistently showed a higher image contrast than the cephalographs taken with standard beam collimation. Despite this, however, there was no significant difference in the reliability of cephalometric measurements between the two groups of films. PMID- 1911690 TI - Bond strengths of orthodontic bonding materials: an in-vitro study. AB - The shear bond strength of a conventional composite resin was compared in-vitro with the bond strength of a fluoride releasing composite and a glass ionomer cement. The results obtained showed that the conventional composite had the highest mean bond strength. The results were also analysed using the Weibull analysis which examines bond reliability rather than mean bond strength. It is likely that the two composites will behave in a similar manner in the clinical situation. PMID- 1911691 TI - A safety adaptation to Interlandi headgear. AB - Extra-oral traction (E.O.T.) to a facebow is used with many types of removable, functional, and fixed orthodontic appliances. A versatile and popular method involves the elastic force being provided by an Interlandi headgear. The facebow, which is of necessity removable, can be displaced from its intra-oral attachments (whilst still connected to the headgear by the elastics) and may result in personal injury. This paper describes a suitable simply made device that can be incorporated to prevent facebow dislodgement, thereby improving safety. PMID- 1911692 TI - A removable appliance for the three-dimensional movement of ectopic maxillary canines. AB - A removable appliance design has been described which is useful in the traction of ectopic canine teeth and is capable of exerting forces in all planes of space, thus optimizing the potential to achieve a stable and aesthetically pleasing result. It does not substitute for the finesse of a fixed appliance, but is a useful tool for when a fixed appliance is not acceptable to the patient. The appliance is cheap to construct, easy to adjust and keep clean, and is well tolerated by patients. PMID- 1911693 TI - Micro-magnetic retainers: an attractive solution to fixed retention. AB - The use of neodymium-iron-boron micro-magnets as a fixed retainer which does not hinder oral hygiene, is reported. A patient with persistent midline spacing treated using this method is described. PMID- 1911694 TI - Medical audit--in relation to orthodontics. AB - A personal interpretation of how Medical Audit will apply to Orthodontics within the hospital environment is presented. The relationships to maintaining statistics, cost effectiveness, resource management, and quality control are discussed. The advantages and disadvantages to the speciality are also considered, particularly in relation to educational and clinical audit. PMID- 1911695 TI - Medical audit for hospital dentistry. PMID- 1911696 TI - Primary failure of eruption. PMID- 1911697 TI - Panel perception of facial attractiveness. PMID- 1911698 TI - Orthodontic interactions: the relationships between the orthodontic services in England and Wales. AB - The manpower distribution and the amount of treatment undertaken by the three orthodontic treatment providing groups was calculated on a national and regional basis. There was marked regional variation in the distribution of orthodontic manpower. It was found that the total orthodontic treatment rate correlated with the distributions of specialist practitioners and general dental practitioners, but not with that of the salaried services. The manpower distribution of specialist practitioners and Community Orthodontists was also related. These results are discussed in terms of the effect of manpower distribution upon demand for treatment and the amount of treatment provided by the orthodontic services. PMID- 1911699 TI - A comparison of orthodontic treatment changes as measured from study casts and cephalometric radiographs. AB - Orthodontic treatment change was examined for 106 consecutively referred patients using serial lateral cephalometric radiographs and study cast records. The 2-D and 3-D measurement systems used to assess the changes were compared for five variables common to both sets of records. No statistical differences were found between the study cast and radiographic records for these variables. The 3-D measurement with the Reflex Metrograph showed marginally better precision in the measurement of the treatment changes examined. However, the main advantage was that it allowed a more thorough and accurate assessment of both individual incisor position and measurement error. PMID- 1911700 TI - Prevalence of familial hyperhomocyst(e)inemia in men with premature coronary artery disease. AB - Elevated plasma levels of homocyst(e)ine have been reported to be more prevalent in patients with coronary artery disease (CAD) than in controls. The purpose of this study was to determine whether this elevation was genetic. We determined homocyst(e)ine levels in 176 men with premature CAD (greater than 50% stenosis of a major epicardial coronary artery occurring before the age of 60 years) and in 255 controls free of cardiovascular disease. Homocyst(e)ine levels were higher in the CAD group compared with controls (13.9 +/- 6.7 versus 10.9 +/- 4.9 nmol/ml, p less than 0.001); in addition, 28% of CAD patients had homocyst(e)ine levels above the 90th percentile of controls. Statistical analysis revealed that homocyst(e)ine levels were not related to the presence of hypertension or diabetes, smoking, or plasma levels of lipoprotein cholesterol and apolipoproteins A-I and B. The families of 71 CAD patients were sampled (selected on the basis of availability of relatives) and included 60 spouses and 239 first degree relatives; 370 subjects were thus sampled. Spearman correlations between probands and spouses (r = 0.264, p = 0.041) and between mean values for parent and offspring (r = 0.356, p = 0.002) for homocyst(e)ine levels indicated that homocyst(e)ine levels are in part genetically determined. In 20 families (28.2%), the proband had homocyst(e)ine levels greater than the 90th percentile; familial segregation was observed in 10 of these kindreds. Therefore, 14% of CAD patients had familial hyperhomocyst(e)inemia. In conclusion, our data suggest that plasma homocyst(e)ine is a risk factor for the development of CAD, independent of other cardiovascular risk factors, and that this elevation is in part genetically determined. PMID- 1911701 TI - Changes in vasoconstrictor and vasodilator responses of the basilar artery during maturation in the Watanabe heritable hyperlipidemic rabbit differ from those in the New Zealand White rabbit. AB - This investigation involved alterations in the local control of vascular tone in the isolated rabbit basilar artery in atherosclerosis, with Watanabe heritable hyperlipidemic (WHHL) rabbits as a model and New Zealand White (NZW) rabbits as controls. Vasoconstrictor responses to KCl in isolated preparations of the basilar artery at basal tone showed no differences at 4, 6, and 12 months of age in either WHHL or NZW rabbits. Contractile responses to both histamine and neuropeptide Y were significantly greater in 12-month-old WHHL rabbit preparations when compared with responses measured at 4 and 6 months. In NZW rabbit preparations, there was no change in maximum contractile responses to both histamine and neuropeptide Y over the same age range. Endothelium-dependent relaxations to acetylcholine in raised-tone preparations from WHHL rabbits were significantly greater at 6 months in comparison with responses measured at both 4 and 12 months of age. In contrast, endothelium-independent relaxations to calcitonin gene-related peptide and vasoactive intestinal polypeptide showed no change over the age range studied. In NZW rabbit preparations, both endothelium dependent and endothelium-independent relaxations declined significantly between 4 and 12 months. The significance of these changes in the rabbit basilar artery in atherosclerosis is discussed in relation to the "protection" of intracranial arteries from atherosclerosis and their subsequent susceptibility to cerebral ischemia and stroke. PMID- 1911702 TI - Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase induce reductase accumulation and altered lamellar bodies in rat forestomach keratinocytes. AB - Lovastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and a potent hypocholesterolemic agent, induces a hyperplastic thickening of the rat forestomach mucosa after oral administration of its active form, a hydroxyacid. We studied the effects of lovastatin on the intracellular accumulation of HMG-CoA reductase immunostaining and the accompanying morphological changes in rat forestomach keratinocytes by immunofluorescence microscopy and transmission electron microscopy (TEM). Administration of lovastatin hydroxyacid induced increases in HMG-CoA reductase levels within forestomach keratinocytes that were dose and time dependent and reversible. The adjacent glandular stomach epithelium did not exhibit induction of reductase. A pharmacologically inactive epimer of lovastatin hydroxyacid did not increase keratinocyte reductase accumulation, and lovastatin lactone induced minimal forestomach reductase. TEM of forestomachs from rats given lovastatin hydroxyacid demonstrated profound alterations in epidermal lamellar bodies (organelles that transport lipids and steroids to the intercellular spaces of the stratum corneum). Treated cells lacked internal lipid lamellae and failed to secrete sheets of lipid material into the intercellular spaces of the stratum corneum. We hypothesize that sustained inhibition of HMG-CoA reductase in rat forestomach keratinocytes induces accumulation of HMG-CoA reductase and hyperplasia by inhibiting sterol synthesis, assembly of lamellar bodies, and formation of intercellular lipid sheets. PMID- 1911704 TI - Native low density lipoprotein. Endothelial cell recruitment of mononuclear cells. AB - The effect of native low density lipoprotein (LDL) on human umbilical vein endothelial cell (EC) recruitment of mononuclear cells (Monos) was investigated. ECs were exposed to LDL at atherogenic concentrations (240 mg cholesterol [Chol]/dl) for as long as 4 days (LDL-treated ECs). LDL-treated ECs bound substantially greater amounts of freshly isolated human monocytes and U937 cells than did control ECs. The enhanced Mono binding was time and LDL concentration dependent. LDL-induced binding was reduced to control levels when cycloheximide was added together with LDL, indicating that de novo protein synthesis was required. Furthermore, this LDL effect was not a general feature of apolipoproteins, as high density lipoprotein in physiologically relevant concentrations (45 mg Chol/dl, 4 days) had no effect on EC-Mono binding. Conditioned media from LDL-treated EC cultures did not increase EC binding of Monos. In contrast, minimally modified LDL increased EC-Mono binding more than eightfold. In conclusion, LDL in concentrations associated with the premature development of atherosclerosis increased EC affinity for Monos. Such LDL-induced alterations in EC physiology likely represent a proinflammatory response and an early step in atherogenesis. PMID- 1911703 TI - Expression of monocyte chemotactic protein and interleukin-8 by cytokine activated human vascular smooth muscle cells. AB - The present study was designed to investigate the capacity of human vascular smooth muscle cells (SMCs) to produce a cytokine chemotactic for monocytes (monocyte chemotactic protein [MCP]) and by way of comparison, a related polypeptide activator of neutrophils (known as interleukin-8 [IL-8] or neutrophil activating protein-1 [NAP-1]. On exposure to IL-1, SMCs released high levels of chemotactic activity for monocytes, which could be removed by absorption with anti-MCP antibodies. MCP production by activated SMCs was comparable to that of IL-1-stimulated umbilical vein endothelial cells. Activated SMCs released appreciable levels of IL-8, as determined by a specific enzyme-linked immunosorbent assay, but little chemotactic activity for neutrophils. IL-1 treated SMCs expressed high levels of both MCP and IL-8 mRNA transcripts, as assessed by Northern blot analysis. Tumor necrosis factor and bacterial lipopolysaccharide but not IL-6 also induced MCP and IL-8 gene expression in SMCs. Nuclear runoff analysis revealed that IL-1 augmented transcription of the MCP and IL-8 genes. The capacity of SMCs to produce a cytokine (MCP) that recruits and activates circulating mononuclear phagocytes may be of considerable importance in the pathogenesis of vascular diseases (e.g., vasculitis and atherosclerosis) that are characterized by monocyte infiltration of the vessel wall. PMID- 1911705 TI - Effect of aspirin and epinephrine on experimentally induced thrombogenesis in dogs. A parallelism between in vivo and ex vivo thrombosis models. AB - Thrombosis on the damaged or ruptured vascular wall in a stenotic coronary artery is believed to be the precipitating factor leading to unstable angina. Little is known about the nature of the interactions among platelets, fluid dynamic factors, and vessel wall properties under such conditions. In the present investigation we have compared two experimental models of thrombosis simultaneously in anesthetized dogs. The first was an in vivo model of unstable angina, in which a fixed circumflex coronary artery stenosis was produced and the resultant cyclic blood flow reductions (CFRs) through the vessel were investigated after infusion of aspirin and a combination of aspirin and epinephrine. As previously reported, aspirin inhibited the CFRs, but the continuous infusion of epinephrine reestablished the appearance of CFRs. The second was an ex vivo model, in which thrombus formation on a type III collagen surface was investigated in a parallel-plate perfusion system under controlled conditions of exposure time and flow; morphological evaluation of thrombus volume, platelet adhesion, and fibrin deposition was performed. The chamber was positioned in an extracorporeal shunt between the carotid artery and the jugular vein of anesthetized dogs and exposed to nonanticoagulated blood at a shear rate of 1,600 sec-1. Thirty minutes after establishment of the CFRs, a blood sample for platelet aggregation was collected and a bleeding time and a first ex vivo perfusion were performed. At the end of this perfusion, animals were subjected either to no treatment (n = 10) or to an intravenous bolus of 10 mg/kg aspirin (n = 7), and a second perfusion was conducted 30 minutes later. Additional untreated animals (n = 6) were given aspirin followed by a continuous intravenous infusion of 10 micrograms/ml epinephrine, and a third perfusion was conducted. Results with respect to platelet adhesion, thrombus volume, and fibrin deposition were similar in the two perfusions in untreated animals. Treatment with aspirin abolished the CFRs in all dogs and concomitantly reduced the ex vivo thrombus volume by 84% (p less than 0.01) without affecting platelet adhesion and fibrin deposition. Bleeding time increased by 40% (p less than 0.05), and collagen induced platelet aggregation was virtually abolished (p less than 0.01). However, infusion of epinephrine in dogs after aspirin treatment restored the CFRs, and the ex vivo thrombus volumes were not statistically different from predrug values. Thus, the ex vivo model satisfactorily reflects the more complicated in vivo model events with respect to intracoronary thrombosis and substantiates the view that aspirin interrupts coronary thrombogenesis in the dog by interfering with platelet cohesion. PMID- 1911706 TI - Lipoprotein lipase activity in skeletal muscle is related to insulin sensitivity. AB - The relative effects of obesity, alone or in combination with insulin resistance and hyperinsulinemia (with or without diabetes), on lipoprotein concentrations, blood pressure, and other risk factors for cardiovascular disease were investigated in 28 men (mean age, 63 years). Special attention was given to lipoprotein lipase (LPL) activity in tissues and to postheparin plasma LPL activity and hepatic lipase activity and their relation to insulin resistance. The 28 men fulfilled the entrance criteria of the study so that they could be allocated to one of the four groups (seven in each group): 1) normal body weight, normal fasting insulin level, and normal glucose tolerance (controls); 2) the same as in group 1 but with moderate obesity; 3) the same as in group 2 but with fasting hyperinsulinemia; 4) the same as in group 3 but with non-insulin dependent diabetes mellitus. Glucose infusion rate for the control group was 8.1 +/- 2.1 mg/kg body wt/min (mean +/- SD) at an insulin infusion rate of 56 milliunits/m2/min. The average values in groups 2, 3, and 4 were 6.0 +/- 0.7, 3.2 +/- 0.5, and 1.9 +/- 1.0 mg/kg body wt/min, respectively. Concentrations of very low density lipoproteins as well as blood pressure and urate concentrations were highest and those of high density lipoproteins were lowest in the two hyperinsulinemic groups (groups 3 and 4). Skeletal muscle LPL activity was 46 +/- 23, 41 +/- 25, 23 +/- 6, and 31 +/- 13 milliunits/g wet wt (mean +/- SD) in the four groups, respectively. There was a positive correlation between glucose infusion rate and muscle LPL activity (r = 0.58, p less than 0.0001). The hepatic lipase activity was positively correlated with the insulin area under the curve of the intravenous glucose tolerance test (r = 0.35, p = 0.02). Furthermore, blood pressure, free fatty acid concentration, liver enzymes, and urate concentrations were significantly correlated with glucose infusion rate at the clamp test. These data give further support for insulin resistance as an important factor behind the observed lipoprotein abnormalities and blood pressure elevations as part of the insulin resistance syndrome characteristic for obese and diabetic patients. PMID- 1911707 TI - Lesion-derived low density lipoprotein and oxidized low density lipoprotein share a lability for aggregation, leading to enhanced macrophage degradation. AB - In this study we assessed whether low density lipoproteins (LDL) isolated from minced aortic atherosclerotic plaques obtained at autopsy (A-LDL) shared structural and functional properties with LDL oxidized by incubation with Cu2+ for 8-18 hours at 20 degrees C (Ox-LDL). Although both A-LDL and Ox-LDL represented monomeric particles about the size of LDL, both differed from LDL in that they showed an increase in electrophoretic mobility relative to LDL, an increase in cholesterol to protein ratio, and an increase in reactivity with a monoclonal antibody that recognizes epitopes on malondialdehyde (MDA)-modified proteins. In addition, both showed an increase in fluorescence at 360 nm excitation, 430 nm emission, an increase in fragmentation of apolipoprotein B with patterns that were quite similar, and an increase in recognition by the scavenger receptor on mouse peritoneal macrophages (MPMs) based on competition of 125I-A-LDL and 125I-Ox-LDL degradation by excess acetylated LDL. In addition, inhibition of degradation by MPMs of 125I-A-LDL and 125I-Ox-LDL by excess unlabeled Ox-LDL and A-LDL were similar. When MDA was added in increasing amounts to labeled LDL and A-LDL, less MDA was required to modify A-LDL than LDl to obtain ligands that were degraded by MPMs to the same degree. Finally, both A-LDL and Ox-LDL but not LDL underwent aggregation (increased metastability) when concentrated to levels exceeding 1 mg protein/ml and showed enhanced macrophage uptake via phagocytosis (inhibition by cytochalasin D). These results demonstrate that A-LDL and Ox-LDL share properties additional to those previously reported, suggesting that oxidation may be a major mode of modification of LDL accumulating in atherosclerotic lesions. This could lead to lipid loading of macrophages induced by phagocytosis of aggregated particles, in addition to unregulated uptake via the scavenger receptor of monomeric particles. PMID- 1911708 TI - Cytokines and growth factors positively and negatively regulate interstitial collagen gene expression in human vascular smooth muscle cells. AB - Human atheromas accumulate extracellular matrix proteins such as collagen types I and III. We tested whether cytokines or growth factors produced by cells found in human atherosclerotic plaques alter collagen gene expression in vascular smooth muscle cells (VSMCs), which produce the blood vessel matrix. Interleukin-1 (IL-1, 1-10 ng/ml) modestly increased the synthesis of collagens I and III (measured by tritiated proline incorporation into specific electrophoretic bands), whereas transforming growth factor-beta (TGF-beta) or platelet-derived growth factor (PDGF) markedly stimulated production of these interstitial collagens. Interferon gamma (IFN-gamma), a product of activated T cells found in atheromas, selectively alters several VSMC functions. For example, this cytokine reduces growth of VSMCs, decreases alpha-actin gene expression, and induces VSMC expression of class II histocompatibility antigens. We report here that IFN-gamma also inhibits basal as well as IL-1-, PDGF-, or TGF-beta-stimulated collagen I and III synthesis by human VSMCs. TGF-beta, the most potent stimulator of collagen synthesis studied here, raised the level of collagen III mRNA in VSMCs 4.8-fold (determined by densitometry of Northern blots), whereas exposure to both TGF-beta and IFN-gamma reduced this mRNA to 0.5 of basal level. Locally produced cytokines and growth factors may thus modify matrix accumulation during atherogenesis by stimulating or suppressing expression of interstitial collagen mRNA and protein by VSMCs. PMID- 1911709 TI - Ultrasonographically assessed carotid morphology and the risk of coronary heart disease. AB - As ultrasonographically assessed carotid arteriosclerosis is being used as a surrogate measure for coronary arteriosclerosis, we performed a prospective longitudinal study of the association of our high-resolution ultrasound assessment of extracranial carotid morphology with the risk of acute coronary events in 1,288 eastern Finnish men. The presence of any structural changes in the common carotid arteries or carotid bulbs was associated with a 3.29-fold (95% confidence interval, 1.31-8.29; p = 0.0074), intimal-medial thickening with a 2.17-fold (95% confidence interval, 0.70-6.74; p = NS), small carotid plaques with a 4.15-fold (95% confidence interval, 1.51-11.47; p less than 0.01), and large ("stenotic") plaques with a 6.71-fold (95% confidence interval, 1.33-33.91; p less than 0.01) risk of acute myocardial infarction compared with men free of any structural changes in the carotid artery wall at baseline. These data confirm the close relation between carotid artery wall morphology and coronary heart disease. PMID- 1911710 TI - Waist to hip ratio in middle-aged women. Associations with behavioral and psychosocial factors and with changes in cardiovascular risk factors. AB - Waist to hip ratio (WHR) was measured in 487 middle-aged women participating in the Healthy Women Study. Upper body fat distribution was found to be associated with numerous behaviors that affect cardiovascular risk, including smoking, low exercise levels, weight gain during adulthood, and higher caloric intake. Moreover, WHR was also associated with higher levels of anger, anxiety, and depression and lower levels of perceived social support. Women with upper body fat obesity had higher systolic blood pressure, total cholesterol, low density lipoprotein cholesterol, triglycerides, and apolipoprotein B and lower levels of high density lipoprotein (HDL) and the HDL subfractions 2 and 3. These associations remained significant after adjusting for body mass index. Among 108 women who had repeat measurements of WHR, changes in WHR over a 3-year period were significantly correlated with changes in activity and with decreases in HDL2. Thus, WHR appears to be an integral component of the cardiovascular risk profile. WHR is related to those behaviors and psychosocial attributes that influence cardiovascular risk. PMID- 1911711 TI - Local modulation of intracellular calcium levels near a single-cell wound in human endothelial monolayers. AB - An endothelial cell monolayer with a single mechanically lysed cell was used as a model to examine the extent, kinetics, and nature of local calcium mobilization in the neighborhood of a wound. Individual endothelial cells from confluent monolayers were mechanically lysed with a minutien needle coupled to a micromanipulator while producing no observable mechanical trauma to the neighboring cells. Changes in calcium levels in individual cells surrounding the wound site were monitored by epifluorescence microphotometry with the calcium sensitive fluorophore indo-1. Individual cells adjacent to the wound site showed a substantial increase in their intracellular calcium levels, almost as high as the calcium levels attained by ionophore controls. The magnitude of intracellular calcium mobilization in confluent monolayers decreased with distance from the wound site, and those cells located at a radius greater than seven cells from the wound site showed no change in their calcium levels. Thus, lysis of a single cell resulted in calcium mobilization in approximately 200 neighboring cells. The time necessary for intracellular calcium to reach maximum levels also increased with distance from the wound site. Calcium mobilization was partly intracellular and was inhibited by disrupting cell-cell coupling or by increasing gap junction resistance by heptanol. This mobilization was greatly attenuated in subconfluent endothelial monolayers, and it was not observed in fibroblasts or smooth muscle cells; furthermore, the effect was defective in monolayers intentionally contaminated with smooth muscle cells. This study examines the extent and possible mechanisms of local endothelial activation near a microscopic endothelial wound. PMID- 1911712 TI - Attenuation of atherosclerosis in a modified strain of hypercholesterolemic Watanabe rabbits with use of a probucol analogue (MDL 29,311) that does not lower serum cholesterol. AB - Probucol is a drug that lowers plasma cholesterol in both humans and animals. In low density lipoprotein (LDL) receptor-deficient Watanabe rabbits, probucol reduces the progression of atherosclerosis. This effect may be attributed to the antioxidant and/or the cholesterol-lowering properties of the drug. In the present report we studied the antiatherogenic effect of a probucol analogue (MDL 29,311) that possesses antioxidant activity but that does not lower cholesterol. Modified Watanabe rabbits (11-12 weeks of age) produced by crossing British Brown and Japanese Watanabe rabbits were fed normal chow (n = 8), chow containing 1% probucol (n = 9), or chow containing 0.1% (n = 9), 0.5% (n = 8), or 1% (n = 6) probucol analogue. After 70 days serum cholesterol levels and the percent area of sudanophilic lesions in the thoracic region of aortas were determined. Total serum cholesterol was significantly lowered (p less than 0.05) in the probucol group (560 +/- 54 mg/dl) compared with that of controls receiving no drug (731 +/ 67 mg/dl) but was not lowered in the analogue groups (722-802 mg/dl). The lesioned area (mean% +/- SEM) in the probucol group (16 +/- 3) was significantly lower (p less than 0.01) than in the controls (52 +/- 8). There were 43 +/- 7%, 33 +/- 8%, and 35 +/- 5% of lesions for the 0.1%, 0.5%, and 1% analogue groups, respectively. After combining the data for the 0.5% and 1% analogue groups, the value (34%) was lower than that of the controls and almost reached significance (p = 0.066). The mean serum drug concentration in the 1% probucol group was 58 +/ 4 micrograms/ml compared with 13 +/- 2, 44 +/- 8, and 74 +/- 8 micrograms/ml for the 0.1%, 0.5%, and 1% analogue groups, respectively. Thus, the decreased effectiveness of the probucol analogue in preventing atherosclerosis could not be explained by a lack of bioavailability. LDLs isolated from rabbits treated with the drug were resistant to Cu(2+)-induced lipid peroxidation, as determined by thiobarbituric acid-reactive substances. The resistance within the analogue groups was dependent on the number of antioxidant molecules per LDL particle. However, there was no significant difference in atherosclerotic lesions between these two groups, suggesting, although not definitively, that the maximal antiatherogenic effect had been reached. Our data suggest that the antioxidant activity of this class of compounds may play an important role in reducing atherosclerosis, but not in reducing cholesterol levels, and that hypocholesterolemic and possibly other activities of probucol might further enhance its antiatherogenic activity. PMID- 1911713 TI - Both circulating and clot-bound plasminogen activator inhibitor-1 inhibit endogenous fibrinolysis in the rat. AB - The effects of both clot-bound and circulating plasminogen activator inhibitor-1 (PAI-1) on endogenous fibrinolysis were investigated in a rat model of pulmonary embolism. Iodine-125 fibrin(ogen)-labeled blood-clot homogenates were delivered through the left jugular vein to the lung microvasculature, and the subsequent extent of the clot lysis was monitored by measuring the release of 125I-fibrin degradation products (FDPs) into the blood. Clots that had incorporated activated PAI-1 ex vivo were subsequently protected from dissolution in vivo in a dose responsive manner (half-maximal concentration [IC50] = 4.3 micrograms/ml). PAI-1 containing clots also resisted lysis, as measured by the release of the specific FDP D-dimer. Plasma levels of plasminogen activator (PA) and PAI activity were unaltered by administration of PAI-1-containing clots, and the clot-protective effects of clot-bound PAI-1 were reversed by exogenous tissue-type plasminogen activator administration. Clot lysis was also inhibited in a dose-responsive manner (IC50 = 58 micrograms/kg) by intravenous bolus delivery of activated PAI-1 to the circulation. The clot-protective effects of circulating PAI-1 were correlated with dose-dependent increases in plasma PAI-1 antigen and activity levels and decreases in plasma PA levels (IC50 = 37 micrograms/ml). There was no evidence of any accumulation of circulating PAI-1 in the lungs. Latent PAI-1, whether delivered with or delivered after the clot homogenates, did not affect the clot-lytic process. Activated and latent PAI-1 was cleared from the circulation in a monophasic manner, with a half-life of approximately 32 and 7 minutes, respectively. The results indicate that both clot-bound and circulating PAI-1 are potent inhibitors of fibrinolysis in vivo. Clot-bound PAI-1 may inhibit PAs in the immediate vicinity of the clots, whereas circulating PAI-1 may act systemically by controlling overall levels of PAs present in the blood. PMID- 1911714 TI - Sluggish sitosterol turnover and hepatic failure to excrete sitosterol into bile cause expansion of body pool of sitosterol in patients with sitosterolemia and xanthomatosis. AB - Sitosterolemia and xanthomatosis are characterized by the development of tendon and tuberous xanthomas at an early age and premature atherosclerosis despite normal plasma cholesterol concentrations. The reason(s) for the xanthoma formation and premature atherosclerosis are not clearly understood. The accumulation of sitosterol in the tissues of these patients could be due to increased uptake of low density lipoprotein (LDL) via LDL receptors because of an expanded sitosterol pool caused by sluggish turnover and decreased excretion of sitosterol into bile and feces coupled with the hyperabsorption of sitosterol. We have studied sitosterol and cholesterol turnovers, the biliary and fecal excretion of neutral and acidic steroids, and the response of plasma sterol (sitosterol and cholesterol) levels to either a sterol-free formula or low plant sterol diet in three patients. The average half-life of the first exponential (tA1/2) for sitosterol was 9.2 +/- 3.3 (mean +/- SD) days, which was more than twice that in normal humans. The second exponential (tB1/2) was 156 +/- 108 days, which was nearly 10 times longer than that for normal humans. The average cholesterol production rate in pool A was 0.87 g/day, which is about 40% of that in normal humans. Cholesterol synthesis measured by the sterol balance technique was also found to be about 70% lower than that for normal humans. In two patients fed a sterol-free formula diet, by 25 days their plasma sitosterol and cholesterol levels had decreased by 42% and 36%, respectively. However, in one patient plasma sitosterol and cholesterol concentrations remained unchanged while on the low plant sterol-mixed food diet.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1911715 TI - Probucol decreases apolipoprotein A-I transport rate and increases high density lipoprotein cholesteryl ester fractional catabolic rate in control and human apolipoprotein A-I transgenic mice. AB - Probucol effects on lipoprotein metabolism were determined in control and human apolipoprotein A-I transgenic (HuAITg) mice. In control mice, probucol reduced total cholesterol from 67 +/- 2 to 25 +/- 2 mg/dl by reducing high density lipoprotein (HDL) cholesterol from 46 +/- 20 to 14 +/- 1 mg/dl and low density lipoprotein (LDL) cholesterol from 11 +/- 1 to 5 +/- 1 mg/dl. Apolipoprotein (apo) A-I levels were reduced from 122 +/- 8 to 56 +/- 5 mg/dl. In HuAITg mice, probucol reduced total cholesterol from 121 +/- 5 to 77 +/- 3 mg/dl by reducing HDL cholesterol from 84 +/- 4 to 56 +/- 3 mg/dl and LDL cholesterol from 19 +/- 2 to 11 +/- 2 mg/dl. Human apo A-I levels were reduced from 267 +/- 13 to 144 +/- 12 mg/dl and mouse apo A-I levels from 18 +/- 2 to 9 +/- 2 mg/dl. Control animals have primarily a monodisperse HDL with a particle diameter of 10 nm. Probucol did not appear to change the particle size distribution in the control animals. The HuAITg mice have a polydisperse HDL with particle diameters of 10.1 and 8.5 nm. Probucol treatment of these animals resulted in HDL with particle diameters of 9.4 and 8.5 nm, apparently reducing the size of the larger particles. In vivo turnover studies revealed that the reduction in apo A-I was primarily due to a decrease in transport rate, whereas the reduction in HDL cholesterol was primarily due to an increase in HDL cholesteryl ester fractional catabolic rate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1911716 TI - Interaction between variant apolipoproteins C-II and E that affects plasma lipoprotein concentrations. AB - The genes for apolipoprotein (apo) C-II, a cofactor for activation of lipoprotein lipase, and apo E, a ligand for receptor-mediated uptake of triglyceride-rich lipoproteins, are physically linked on chromosome 19q13.1. In a large Caribbean Caucasian family, several individuals had clinical features of the complete absence of lipoprotein lipase activity and were homozygous for a DNA frameshift mutation of apo C-II, imparting functional inactivity to the mutant protein. Plasma from heterozygous carriers of this mutation, when compared with plasma from relatives who were noncarriers, had significantly diminished capacity to activate lipoprotein lipase in vitro. We also observed in heterozygotes for this mutation a wide range of serum lipid and lipoprotein levels. When age and sex were taken into account, the presence of a single apo E allele encoding the E4 isoform occurring in individuals with a single mutant apo C-II allele was strongly associated with higher levels of cholesterol, triglycerides, very low density lipoprotein cholesterol, and non-high density lipoprotein cholesterol when compared with those of relatives who carried neither or only one variant allele. This suggests that a single genetic mutation that usually has a recessive effect on lipoprotein metabolism can have an interactive effect on lipid phenotype when it is coinherited with a single mutation at another gene whose product affects the same metabolic pathway. PMID- 1911717 TI - Overexpression of low density lipoprotein receptor on Chinese hamster ovary cells generates foam cells. AB - The atherosclerotic lesion is characterized by the presence of cholesterol-loaded foam cells. Chinese hamster ovary (CHO) cells do not normally store cholesteryl esters because low density lipoprotein (LDL) receptors are suppressed by exposure of these cells to LDL cholesterol. We transfected LDL receptor cDNA linked to the simian virus 40 early promoter into CHO cells (CHO 29) and found that LDL receptor binding in these cells was not suppressed by an excess amount of LDL cholesterol, indicating no regulation of the LDL receptor in CHO 29 cells. Furthermore, CHO 29 cells showed a high activity of LDL uptake and intracellular accumulation of cholesteryl esters. Light-microscopic examination demonstrated the resulting formation of foam cells in CHO 29 cells in the presence of 5 micrograms LDL/ml. These results demonstrated that foam cell changes in atherosclerotic lesions can be reproduced in CHO cells, whose LDL receptor activity is overexpressed, through the mechanism of LDL receptor-mediated endocytosis of native LDL. PMID- 1911718 TI - Effects of human recombinant macrophage colony-stimulating factor on the secretion of lipoprotein lipase from macrophages. AB - The effects of human recombinant macrophage colony-stimulating factor (M-CSF) on the secretion of lipoprotein lipase were studied in rat alveolar macrophages. Five nanograms per milliliter M-CSF significantly enhanced lipoprotein lipase secretion (threefold), and the maximal effect (10-fold) of M-CSF on lipoprotein lipase secretion was observed at a dose of 200 ng/ml M-CSF. The effect of M-CSF was time dependent but was not manifested during the first 8 hours of incubation. After 24 hours, its effects were evident and dose dependent. On blot hybridization of macrophage RNAs with human cDNA of lipoprotein lipase, a remarkable and dose-dependent increase in mRNA level (7.3-fold) was found in M CSF-treated alveolar macrophages. The secretion of lipoprotein lipase was also enhanced in human monocyte-derived macrophages (2.6-fold), whereas the secretion from either THP-1 cells, P388 cells, or J774 cells was not significantly enhanced. These results indicate that the stimulation of lipoprotein lipase secretion after M-CSF treatment was evident in rat alveolar macrophages and human monocyte-derived macrophages on the basis of both enzyme activity and mRNA level; therefore, M-CSF may be involved in lipoprotein metabolism of macrophages through modulation of the secretion of lipoprotein lipase. PMID- 1911719 TI - Effects of copper and histidine on oxidative modification of low density lipoprotein and its subsequent binding to collagen. AB - It was previously shown that serum low density lipoprotein (LDL) binds to type I collagen gels and that the binding is increased after modification by cultured endothelial cells. It is now demonstrated that when LDL is incubated with cells cultured in Dulbecco's modified minimal essential medium (DMEM), the subsequent binding of LDL to collagen is considerably less than after incubation with endothelial cells cultured in Ham's F-12 medium (F12). To determine the reason for this difference, collagen gels were made with saline containing ingredients of DMEM individually or in groups, and binding of LDL to such gels was measured. Modification of LDL, manifested by a high level of binding to the collagen, by lipid peroxidation (production of thiobarbituric acid-reactive substances), and by increased electrophoretic mobility occurred on exposure to collagen gels made in saline; these changes were almost completely inhibited by the addition of histidine at a concentration equal to that in DMEM. They were also inhibited by butylated hydroxytoluene, desferrioxamine, and EDTA; penicillamine and hydroxyl radical scavengers inhibited collagen binding but did not inhibit lipid peroxidation or the increase in electrophoretic mobility. Nominally, DMEM contains 270 microM histidine but no copper, whereas F12 contains 135 microM histidine and 10 nM copper; addition of copper (as much as 5 microM) to DMEM or of histidine (as much as 2.16 mM) to F12 did not overcome the differences between the media in supporting LDL oxidation by endothelial cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1911721 TI - Enhanced uptake and impaired intracellular metabolism of low density lipoprotein complexed with anti-low density lipoprotein antibodies. AB - We have previously shown that incubation of human macrophages with antigen antibody complexes prepared with native human low density lipoprotein (LDL) and rabbit anti-LDL antibodies (LDL-ICs) results in an increased intracellular accumulation of cholesteryl esters (CEs) and induces a marked increase in the number of LDL receptors. To determine whether the increased CE accumulation in these cells occurred during incubation of the cells with LDL-ICs or whether it was secondary to the uptake of LDL by overexpressed LDL receptors, we incubated human macrophages with LDL-ICs for 22 hours, followed by incubation with native LDL for another 20 hours. We found that about 90% of the accumulated CEs could be accounted for by the first incubation with LDL-ICs. We then proceeded to show that the CEs accumulated during incubation of cells with LDL-ICs was secondary to enhanced uptake and impaired degradation of the LDL complexed with immunoglobulin G (IgG) (LDL-IC), which led to a marked intracellular accumulation of undergraded LDL (levels 199-fold higher than those obtained when the cells were incubated with the same concentration of native LDL not complexed with IgG). We have also shown that not all CEs accumulated in these cells were derived from accumulation of undegraded LDL and that some of them were derived from the reesterification of free cholesterol released during hydrolysis of LDL. LDL-ICs promoted increased CE accumulation and foam cell formation at concentrations as low as 25 micrograms/ml. To determine which receptors were involved in the uptake of LDL ICs, we performed experiments in which the uptake of LDL-ICs was competitively inhibited with heat-aggregated gamma globulin, native LDL, beta-very low density lipoprotein, or acetylated LDL. Our results demonstrated that LDL-IC uptake was most effectively inhibited by heat-aggregated gamma globulin, partially inhibited by native LDL or by a monoclonal antibody to the LDL receptor, and not inhibited by acetylated LDL or beta-very low density lipoprotein. Thus, we conclude that the majority of LDL-ICs are taken up through Fc gamma receptors. Finally, we investigated whether the increase in LDL receptor expression was dependent on the receptor pathway used by the LDL-ICs, and we were able to demonstrate that when macrophages were incubated with LDL-ICs prepared with F(ab')2 fragments of the anti-LDL antibody, LDL receptor expression was not enhanced. Therefore, we postulate that the uptake of LDL-ICs through Fc gamma receptors results in an uncoupling of the normal regulation of the LDL receptor expression. PMID- 1911720 TI - Effects of polymorphisms in apolipoproteins E, A-IV, and H on quantitative traits related to risk for cardiovascular disease. AB - The impact of the common alleles at structural loci coding for apolipoprotein (apos) A-IV, E, and H on 12 quantitative risk factors for cardiovascular disease (apos A-I, A-II, B, C-II, C-III, and E; total cholesterol; triglycerides; high density lipoprotein cholesterol; systolic blood pressure; diastolic blood pressure; and red blood cell sodium-lithium countertransport) was estimated in 453 unrelated individuals (227 men and 226 women) aged 26-63 years from the Rochester Family Heart Study, who were not using medications affecting lipid levels or blood pressure. Each risk factor was adjusted for concomitants (assay date, age, age, squared, height, weight and smoking status) before the genotypic effects on mean levels and variances were estimated. Allele frequencies were the same in men and women and were similar to those observed in other studies of US Caucasians. There were very different gender-specific estimates of the relative contribution of concomitants, measured genetic effects, and residual unexplained effects to the interindividual variation of particular traits. Allelic variation in apo E had effects on the greatest number of traits, namely apo E, apo B, apo C II, and total cholesterol. An effect on triglycerides was dependent on the inclusion of hypertriglyceridemic subjects. Allelic effects of apo A-IV and apo H were much less than those estimated for the apo E polymorphism. A possible role for apo H in high density lipoprotein metabolism is suggested. This study indicates that variation in many genes may influence variation in a particular trait and that a particular gene may have pleiotropic effects on several traits. PMID- 1911722 TI - Serum low density lipoprotein cholesterol level and cholesterol absorption efficiency are influenced by apolipoprotein B and E polymorphism and by the FH Helsinki mutation of the low density lipoprotein receptor gene in familial hypercholesterolemia. AB - The aim of the present study was to evaluate the effect of variation of different gene loci separately and in concert on lipid metabolism in heterozygous familial hypercholesterolemia (FH). We assayed a unique low density lipoprotein (LDL) receptor gene defect (designated as FH-Helsinki), the XbaI polymorphism of the apolipoprotein (apo) B, phenotypes of the apo E, and determined the levels of serum lipoproteins, the efficiency of cholesterol absorption, and the values for several parameters of cholesterol metabolism in 51 unrelated patients with heterozygous FH. The genetic parameters were distributed independently of each other. Gender distribution and the prevalence of coronary artery disease were similar in the different apo E phenotypes, in the apo B genotypes, and in patients with and without the FH-Helsinki mutation. However, the FH-Helsinki mutation was associated with an increased body mass index. Serum LDL cholesterol was significantly elevated in patients with the FH-Helsinki mutation and the apo B X2 allele. Apo E phenotypes were not related to serum lipids per se, but the highest serum LDL cholesterol levels were measured in patients with the FH Helsinki gene, apo E4 phenotype, and at least one X2 allele. Patients with the FH Helsinki mutation and apo E4 phenotype had the highest cholesterol absorption efficiency. Cholesterol absorption was not related to serum lipids or lipoproteins, but LDL cholesterol was most elevated in patients with the most efficient cholesterol absorption. We conclude that in FH, diverse genetic factors exert individual and additive influences on serum LDL cholesterol levels. PMID- 1911723 TI - Aortic intimal thickening and myosin isoform expression in hyperthyroid rabbits. AB - The potential effect of thyroid hormones on the expression of cytoskeletal and cytocontractile proteins of vascular smooth muscle cells (SMCs) was examined by a panel of monoclonal antibodies and immunocytochemical procedures. L-Thyroxine was administered to adult New Zealand White rabbits for as long as 26 days, and the aortic SMC composition was studied at days 1, 2, 7, 15, and 26 from the beginning of hormonal treatment. A diffuse intimal thickening of the aorta became visible after 7 days of thyroxine administration. Histological and histochemical examination of intimal tissues from hyperthyroid rabbits revealed the presence of a homogeneous Sudan black-negative cell population. In immunofluorescence tests the intimal cells were found to be negative for antibodies specific for monocyte/macrophage or desmin and homogenously reactive (positive) for antibodies to vimentin and smooth muscle (SM) alpha-actin, thus indicating that cells present in the thickened intima were of the SM type. In addition, intimal SMCs from aortas of hyperthyroid rabbits showed a myosin isoform content similar to that found in normal developing aortic SM and in a specific medial SMC subpopulation of aortas from adult euthyroid animals. In the media underlying the intimal thickening, almost all the SMCs switched their myosin isoform expression toward the "immature" phenotype after 2 days of thyroxine treatment. When the level of thyroid hormones was reduced by propylthiouracil treatment, the medial SMC subpopulation with the immature myosin isoform content present in euthyroid rabbits completely disappeared. The study of DNA synthesis-related bromodeoxyuridine incorporation in aortas from hyperthyroid rabbits showed the presence of labeled nuclei in medial SMCs before the appearance of the intimal thickening as well as in the thickened intima and in the underlying media at days 7 and 15. These results are consistent with a specific role for thyroid hormones in inducing proliferation/migration of medial SMCs into the intima. Moreover, the switch in the expression of myosin isoforms induced by thyroid hormones appears to precede the accumulation of medial SMCs in the intima. PMID- 1911724 TI - [Subependymal giant cell astrocytoma]. AB - Subependymal giant-cell astrocytomas (SEGA) are rare brain tumors. They occur typically in the walls of the lateral ventricles and very seldom in the wall of the third ventricle. In our experience, all patients with SEGA have had tuberous sclerosis. Between January 1950 and May 1990, of our 345 patients with tuberous sclerosis 22 were found to have SEGA. The diagnosis being made histologically in symptomatic cases or by clinical or neuroradiologic methods. The histological, immunohistochemical and ultrastructural features of this unique tumor are discussed. To date, histopathologic methods have not resolved the issue of whether these tumors are exclusively astrocytic or neuronal in nature, or show features of both. Modern immunohistochemical and/or molecular-biological techniques will no doubt elucidate the histogenesis of this highly characteristic, albeit polymorphous tumor. PMID- 1911725 TI - Adreno-hepatic fusion. An autopsy study. AB - Adreno-hepatic fusion (AHF) is defined as adhesion of the liver and right adrenal cortex with close intermingling of the respective parenchymal cells. Contrary to the general opinion, AHF is a rather common event of unknown biological significance: AHF was exhibited by 63 of 636 unselected autopsy cases (9.9%). Its incidence is much higher in older age groups, suggesting that AHF may be an ageing phenomenon. No causative relationship was found to exist between occurrence of AHF and pathological conditions of both organs. PMID- 1911726 TI - [Analgesic nephropathy (AN) with special reference to capillary sclerosis. A multicenter study from the former East Germany]. AB - The incidence of capillary sclerosis in the mucosa of the upper urinary tract was beyond expectation, according to a multicenter study conducted at 11 pathological institutes in all regions of the former GDR from which the following more specific findings were obtained: Capillary sclerosis was recorded primarily from women (1.4:1) in 3.6% of 3,929 autopsy cases (minimum age being 40 years). This result has close to the outcome of a study conducted in Basle, Switzerland, though highest severity (0.33%) and the complete morphological picture of analgesic nephropathy (0.54%) were clearly less frequent, as compared to the above Swiss findings. No reliable conclusion can as yet be drawn regarding the infrequent case of renal pelvis carcinoma. Epidemiological and clinical studies are likely to suggest that an increase in findings might be expected in this part of Germany and might be aetiologically attributable to abuse of analgesics. PMID- 1911727 TI - Magnesium in cross bands of injured myocytes. AB - Magnesium was found to accumulate in cross bands of myocytes due to myofibrillar degeneration in the context of myocardial lesions and was also detected from contraction bands in injured fibres of duck feather muscles. Relevant findings were based on histochemical detection of magnesium with quinalizarin, magnesone, and titan-yellow. Amassed degenerated myofibrils and injured mitochondria were supposed to make for the substrate of magnesium. Elective staining of cross bands by Luxol Fast Blue MBS was assumed to be attributable to bondability to divalent cations. PMID- 1911728 TI - [Creutzfeldt-Jakob disease and Gerstmann-Straussler syndrome with reference to their differential diagnosis]. AB - Differential diagnosis has quite often proved to be difficult between CREUTZFELDT JAKOB disease (CJD) and GERSTMANN-STRAUSSLER syndrome. Clinical and morphological aspects as well as the pathological course and differential diagnosis of CJD and Gerstmann-Strussler syndrome are discussed in some detail. Slow influence can be morphologically diagnosed with reference to the overall pattern of individual alterations with inclusion of scrapie-associated fibrils. This morphological diagnosis can be verified by experimental inoculation to susceptible animals. PMID- 1911729 TI - [Merkel cell tumor (neuroendocrine carcinoma of the skin) in an unusual location. Immunohistochemical and lectin histochemical findings]. AB - Neuroendocrine carcinoma of the skin usually occurs in elderly individuals. Head and neck are the most common primary sites followed by the extremities and trunk. As this tumor represents a remarkable rarity in younger people, we report the case of a 33-year-old woman with a neuroendocrine carcinoma in an unusual localization. Diagnosis was based on the results of the examination of a metastasis in the inguinal lymph nodes. The lesion at the Labium minus pudendi which is to be considered the primary tumor was detected several months later. Diagnosis of Merkel cell tumor until recently had depended on ultrastructural demonstration of dense-core membrane-bound granules. Today, diagnosis can be secured also by optical light microscopy, on the basis of a certain constellation of immunohistochemical and lectin histochemical findings. PMID- 1911730 TI - Functioning "black adenoma" of the adrenal gland with emphasis on ultrastructural studies. AB - An account is given in this paper of functional black adenoma of the adrenal cortex. Autonomous hormone secretion of the tumour was confirmed by pre- and postoperative biochemical tests. Electron microscopy revealed two types of pigment granules. Mitochondria showed severe impairment. A relationship was assumed to exist between mitochondrial alterations and accumulation of lipoid containing pigment because of the important role of mitochondria in lipid metabolism. Abnormal collagen fibrils were found in the cytoplasm of tumour cells. Comparison of the presented black adenoma with two nonpigmented adrenal adenomas showed the ultrastructure of black-adenoma cells to be similar to the compact cells of "yellow" cortical adenomas. However, the latter contained normal mitochondria and one type of pigment granules. Adrenal black adenoma thus can be regarded as a pathological entity. PMID- 1911731 TI - [Sellar germinoma with lung metastases]. AB - Reported in this paper is the case of a boy aged 15 years with sellar germinoma which led to one singular pulmonary metastasis, three years after subtotal surgical removal and subsequent successful irradiation of the tumor rest. The primary tumor together with the lung metastasis were characterised as germinoma with trophoblastic giant cells as additional elements. Interpretation of the pulmonary tumour was somewhat difficult, since diagnosis of the primary tumor had encouraged assumption of a chromophobic hypophyseal adenoma with polymorphic manifestation, with no relationship between the intracranial and pulmonary tumors being presumed by the surgeon. The true nature of the metastasis and, consequently, the histogenetic identity of both tumors was cleared up by immunohistochemical detection of beta-HCG in almost all syncytiotrophoblasts. Comprehensive analysis of the literature on metastasising intracranial germinomas may be helpful in disclosing possible relationships between the histological type of a primary tumor or neurosurgical action and the metastatic potential of tumors. PMID- 1911733 TI - [Carl Ludwig Homburg. A prosector in Goethe's time]. AB - The interest of the medical historian is not necessarily confined to great scholars but can be devoted, as well, to assistant like Homburg who had been not only the prosector of J. C. Loder, anatomist in Jena but had, at the same time, worked for J. W. v. Goethe, Cabinet Minister in Weimar and in charge of Jena University. Some data on the life of prosector C.L. Homburg (who died in 1833) are known to us from notes and letters of Goethe and Loder. Loder had employed the former Berlin student of surgery and barber's assistant to model for him anatomic samples for demonstration and anatomic illustrations and also for his collection. When Loder followed a call to Halle and took his collection of specimens along with him, his successor in Jena had to set up another collection which came under ducal administration. Homburg gave him a helping hand, under Goethe's vigilant control. Loder sold his collection to Russia, some time later, and had an Anatomic Theatre built in Moscow for its accommodation and for anatomic lectures. For that purpose, he called Homburg from Jena and praised him in his public inauguration speech. Two sons and one grandson of Homburg are known to have worked as prosectors, as well, in Moscow, Kharkov, and Kazan. PMID- 1911732 TI - [Diffuse malignant mesothelioma of the pericardium]. AB - Reported in this paper is the morphological appearance of a diffuse malignant mesothelioma in a male patient aged 39 years. The tumour parenchyma was primarily made up of fusiform and giant cells. Glandular structures were rarely observed. Immunohistochemical investigation revealed negative staining for CEA and positive staining for vimentin. PMID- 1911734 TI - [Pathology of the placenta. V. Circulatory disorders of the placenta. Fetal vascular system]. AB - Discussed are circulatory disorders as well as pathologico-anatomic findings recordable from fetal vessels of the placenta. Thorough reference is first made to obliterative endoarteritis of the greater arteries. Its forms are described, with formal and causative pathogenesis being discussed. Conclusive coverage of causative pathogenesis has proved to be possible only for unambiguously determined inflammatory manifestations (rubella, lues). The second major complex covers alterations to greater and minor fetal vessels which are characterized by central parietal thrombosis (possibly associated with fetal asphyxia) and peripherally disseminated intravasal coagulation (associated with peripartal shock or other conditions). Included in the latter group of alterations are congenital pulmonary hyaline membranes (perhaps also some membranes of postnatal origin) which are, as well, considered as shock equivalent. PMID- 1911735 TI - A case of "subjective" Fregoli syndrome. AB - In the classic type of Fregoli syndrome, the affected person believes that another person's mind can inhibit the body of another person. We present an unusual presentation of Fregoli syndrome in which a patient believed that copies of his own mind inhabited the bodies of others. Given that the misidentification syndrome called subjective doubles involves the delusional belief that one's own physical double exists, by analogy this patient suffered from "subjective" Fregoli syndrome. PMID- 1911737 TI - Characterization of 5-HT1D receptor binding sites in post-mortem human brain cortex. AB - The present study provides further evidence for the presence of serotonin1D (5 HT1D) receptors in post-mortem human brain. Receptor binding parameters in temporal cortex homogenates were assessed using [3H]5-HT in the presence of 100 nM 8-OH-DPAT, 1 microM propranolol and 1 microM mesulergine to prevent labelling of the 5-HT1A, 5-HT1B and 5-HT1C sites, respectively. Under these conditions, [3H]5-HT apparently bound to a class of high affinity (Kd = 5.0 +/- 1.0 nM) low capacity (Bmax = 96 +/- 23 fmol/mg protein) sites. In competition experiments, 5 HT and 5-carboxyamidotryptamine (5-CT), as well as ergotamine, lysergic acid, sumatriptan and RU-24969 exhibited high affinity for these sites. This pharmacological profile is concordant with the ligand selectivity pattern reported for 5-HT1D receptors in other species and thus provides further evidence for its existence in human temporal cortex. In addition, the competition profile of some ligands, particularly of unlabelled 5-HT, 5-CT and ergotamine, revealed the existence of a lower affinity binding site. The latter suggests receptor heterogeneity or the presence of a lower affinity state of 5-HT1D receptors. PMID- 1911738 TI - "Les psychoses passionnelles" reconsidered: a review of de Clerambault's cases and syndrome with respect to mood disorders. AB - While de Clerambault's name has been linked to erotic delusions, he attempted to describe "pure" erotomania as a paradigm of a broader group of delusions. His own cases and a large number in the English and French literature seem to indicate that severe mood disorder, most likely bipolar affective disorder, is responsible for a portion of the erotomanic delusions. The concept of "les psychoses passionnelles" in the context of French psychiatry is reviewed. PMID- 1911739 TI - Dose ranging study of the effects of cholecystokinin in healthy volunteers. AB - The authors determined whether response to cholecystokinin-tetrapeptide (CCK-4) was dose-dependent. Healthy volunteers (n = 36) received double-blind injections of either 9 micrograms, 25 micrograms, or 50 micrograms of CCK-4 and placebo in a randomized sequence of injection. Significant dose-related differences were found for the number of symptoms, sum intensity of symptoms and the time until onset of symptoms, but not for the duration of symptoms. The incidence of panic attacks with CCK-4 was 11%, 17% and 47% for the 9 micrograms, 25 micrograms and 50 micrograms dose, respectively. None of the controls panicked with placebo injections. These results support the notion of a dose-dependent effect of CCK-4 induced panic symptoms. Implications of these findings in the neurobiology of panic attacks are discussed. PMID- 1911736 TI - Structural and functional brain imaging in schizophrenia. AB - We present an evaluation of the contribution of structural and functional brain imaging to our understanding of schizophrenia. Methodological influences on the validity of the data generated by these new technologies include problems with measurement and clinical and anatomic heterogeneity. These considerations greatly affect the interpretation of the data generated by these technologies. Work in these fields to date, however, has produced strong evidence which suggests that schizophrenia is a disease which involves abnormalities in the structure and function of many brain areas. Structural brain imaging studies of schizophrenia using computed tomography (CT) and magnetic resonance imaging (MRI) are reviewed and their contribution to current theories of the pathogenesis of schizophrenia are discussed. Positron emission tomography (PET) studies of brain metabolic activity and dopamine receptor binding in schizophrenia are summarized and the critical questions raised by these studies are outlined. Future studies in these fields have the potential to yield critical insights into the pathophysiology of schizophrenia; new directions for studies of schizophrenia using these technologies are identified. PMID- 1911740 TI - Growth hormone and cortisol secretion in relation to sleep and wakefulness. AB - The study investigated secretory patterns of growth hormone (GH) and cortisol in relation to sleep and wakefulness. Plasma hormone levels were monitored in 10 young men during baseline waking and sleeping, during 40 hours of wakefulness, and during sleep following deprivation. The normal nocturnal GH surge disappeared with sleep deprivation, and was intensified following sleep deprivation. Mean GH levels were higher during slow wave sleep (SWS) compared with other sleep stages. During sleep after deprivation, GH secretion was prolonged, and second GH peaks occurred in three subjects which were not associated with SWS. Average 24-hour cortisol levels were not altered by sleep deprivation or sleep following deprivation, but the nocturnal cortisol rise occurred approximately one hour earlier with sleep deprivation and one hour later with resumed sleep, compared to baseline. This effect on the timing of the rise is consistent with an initial inhibitory influence of sleep on cortisol secretion. The results demonstrate that: the nocturnal growth hormone surge is largely sleep-dependent; temporal associations between GH and SWS are not reliable after sleep deprivation; although the cortisol rhythm is not sleep-dependent, the timing of the cortisol rise may be influenced by sudden changes in the sleep-wake schedule. PMID- 1911741 TI - Kinetic characterization of phospholipase A2 modified by manoalogue. AB - Manoalogue, a synthetic analogue of the sea sponge-derived manoalide, has been previously shown to partially inactivate the phospholipase A2 from cobra venom (Reynolds, L. J., Morgan, B. P., Hite, E. D., Mihelich, E. D., & Dennis, E. A. (1988) J. Am. Chem. Soc. 110, 5172) by reacting with enzyme lysine residues. In the present study, the inactivation of the phospholipases A2 from pig pancreas, bee venom, and cobra (Naja naja naja) venom by manoalogue was studied in detail. Manoalogue-treated enzymes were examined in the scooting mode on vesicles of 1,2 dimyristoyl-sn-glycero-3-phosphomethanol. Here the native enzymes bound irreversibly to the vesicles and hydrolyzed all of the phospholipids in the outer monolayer without leaving the surface of the interface. All three manoalogue treated enzymes showed reduced catalytic turnover for substrate hydrolysis in the scooting mode, and the modified enzymes did not hop from one vesicle to another. Thus, inactivation by manoalogue is not due to the decrease in the fraction of enzyme bound to the substrate interface. This result was also confirmed by fluorescence studies that directly monitored the binding of phospholipase A2 to vesicles. A chemically modified form of the pig pancreatic phospholipase A2 in which all of the lysine epsilon-amino groups have been amidinated was not inactivated by manoalogue, indicating that the modification of lysine residues and not the amino-terminus is required for the inactivation. Several studies indicated that the manoalogue-modified enzymes contain a functional active site. For example, studies that monitored the protection by ligands of the active site from attack by a alkylating agent showed that manoalogue-modified pig phospholipase A2 was capable of binding calcium, a substrate analogue, lipolysis products, and a competitive inhibitor. Furthermore, relative to native enzymes, manoalogue-modified enzymes retained significantly higher catalytic activities when acting on water-soluble substrates than when acting on vesicles in the scooting mode. Intact manoalogue had no affinity for the catalytic site on the enzyme as it did not inhibit the enzyme in the scooting mode and it did not protect the active site from alkylation. Pig pancreatic phospholipase A2 bound to micelles of 2-hexadecyl-sn-glycero-3-phosphocholine was resistant to inactivation by manoalogue, suggesting that the modification of lysine residues on the interfacial recognition surface of the enzyme was required for inactivation.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1911742 TI - Activation of methionine by Escherichia coli methionyl-tRNA synthetase. AB - In the present work, we have examined the function of three amino acid residues in the active site of Escherichia coli methionyl-tRNA synthetase (MetRS) in substrate binding and catalysis using site-directed mutagenesis. Conversion of Asp52 to Ala resulted in a 10,000-fold decrease in the rate of ATP-PPi exchange catalyzed by MetRS with little or no effect on the Km's for methionine or ATP or on the Km for the cognate tRNA in the aminoacylation reaction. Substitution of the side chain of Arg233 with that of Gln resulted in a 25-fold increase in the Km for methionine and a 2000-fold decrease in kcat for ATP-PPi exchange, with no change in the Km for ATP or tRNA. These results indicate that Asp52 and Arg233 play important roles in stabilization of the transition state for methionyl adenylate formation, possibly directly interacting with complementary charged groups (ammonium and carboxyl) on the bound amino acid. Primary sequence comparisons of class I aminoacyl-tRNA synthetases show that all but one member of this group of enzymes has an aspartic acid residue at the site corresponding to Asp52 in MetRS. The synthetases most closely related to MetRS (including those specific for Ile, Leu, and Val) also have a conserved arginine residue at the position corresponding to Arg233, suggesting that these conserved amino acids may play analogous roles in the activation reaction catalyzed by each of these enzymes. Trp305 is located in a pocket deep within the active site of MetRS that has been postulated to form the binding cleft for the methionine side chain.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1911743 TI - Selective proteolytic cleavage of recombinant human interleukin 4. Evidence for a critical role of the C-terminus. AB - Human interleukin 4 is a 129 amino acid lymphokine secreted by activated T cells that exerts pleiotropic biological effects on B and T lymphocytes and other hematopoietic cells. Structure-function relations were studied by employing selective proteolytic cleavage of purified recombinant human interleukin 4 (rhuIL 4). Limited proteolysis with endoprotease Glu-C from Staphylococcus aureus (V8) produced two digestion products that were observed on sodium dodecyl sulfate polyacrylamide gel electrophoresis with apparent molecular weight values of 19K (I) and 15K (II), respectively. These species were isolated by reversed-phase HPLC. Amino acid sequencing indicated that species II was an 84 amino acid core fragment extending from Gln-20 to Glu-103 and containing a hydrolyzed peptide bond at Glu-26. On the basis of known disulfide bond assignments, it was concluded that species II was stabilized by two disulfide bonds (Cys-24/Cys-65 and Cys-46/Cys-99). Analysis of its secondary structure by circular dichroism revealed a high content of alpha helix. Species I was the full-length rhuIL-4 with selective cleavage at Glu-26 and Glu-103. Both species I and II were inactive in an in vitro assay based on proliferation of peripheral blood lymphocyte blasts and lacked the ability to bind to teh rhuIL-4 receptor on Daudi cells. In order to elucidate further the role of the residues removed by S. aureus V8 protease, rabbit antisera were raised to synthetic peptides corresponding to residues 1-26 at the N-terminus and 104-129 at the C-terminus. Only antisera directed to the C-terminal peptide inhibited binding of 125I-rhuIL 4 to Daudi cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1911744 TI - Structure of the IIA domain of the glucose permease of Bacillus subtilis at 2.2-A resolution. AB - The crystal structure of the IIA domain of the glucose permease of the phosphoenolpyruvate:sugar phosphotransferase system (PTS) from Bacillus subtilis has been determined at 2.2-A resolution. Refinement of the structure is in progress, and the current R-factor is 0.201 (R = sigma h parallel Fo magnitude of - Fc parallel/sigma h magnitude of Fo, where magnitude of Fo and magnitude of Fc are the observed and calculated structure factor amplitudes, respectively) for data between 6.0- and 2.2-A resolution for which F greater than or equal to 2 sigma (F). This is an antiparallel beta-barrel structure that incorporates "Greek key" and "jellyroll" topological motifs. A shallow depression is formed at the active site by part of the beta-sheet and an omega-loop flanking one side of the sheet. His83, the histidyl residue which is the phosphorylation target of HPr and which transfers the phosphoryl group to the IIB domain of the permease, is located at the C-terminus of a beta-strand. The N epsilon atom is partially solvated and also interacts with the N epsilon atom of a second histidyl residue, His68, located at the N-terminus of an adjacent beta-strand, suggesting they share a proton. The geometry of the hydrogen bond is imperfect, though. Electrostatic interactions with other polar groups and van der Waals contacts with the side chains of two flanking phenylalanine residues assure the precise orientation of the imidazole rings. The hydrophobic nature of the surface around the His83-His68 pair may be required for protein-protein recognition by HPr or/and by the IIB domain of the permease. The side chains of two aspartyl residues, Asp31 and Asp87, are oriented toward each other across a narrow groove, about 7 A from the active-site His83, suggesting they may play a role in protein protein interaction. A model of the phosphorylated form of the molecule is proposed, in which oxygen atoms of the phosphoryl group interact with the side chain of His68 and with the main-chain nitrogen atom of a neighboring residue, Val89. The model, in conjunction with previously reported site-directed mutagenesis experiments, suggests that the phosphorylation of His83 may be accompanied by the protonation of His68. This may be important for the interaction with the IIB domain of the permease and/or play a catalytic role in the phosphoryl transfer from IIA to IIB. PMID- 1911745 TI - Construction of a functional lactose permease devoid of cysteine residues. AB - By use of oligonucleotide-directed, site-specific mutagenesis, a lactose (lac) permease molecule was constructed in which all eight cysteinyl residues were simultaneously mutagenized (C-less permease). Cys154 was replaced with valine, and Cys117, -148, -176, -234, -333, -353, and -355 were replaced with serine. Remarkably, C-less permease catalyzes lactose accumulation in the presence of a transmembrane proton electrochemical gradient (interior negative and alkaline). Thus, in intact cells and right-side-out membrane vesicles containing comparable amounts of wild-type and Cys-less permease, the mutant protein catalyzes lactose transport at a maximum velocity and to a steady-state level of accumulation of about 35% and 55%, respectively, of wild-type with a similar apparent Km (ca. 0.3 mM). As anticipated, moreover, active lactose transport via C-less permease is completely resistant to inactivation by N-ethylmaleimide. Finally, C-less permease also catalyzes efflux and equilibrium exchange at about 35% of wild-type activity. The results provide definitive evidence that sulfhydryl groups do not play an essential role in the mechanism of lactose/H+ symport. Potential applications of the C-less mutant to studies of static and dynamic aspects of permease structure/function are discussed. PMID- 1911746 TI - Ca(2+)-dependent annexin self-association on membrane surfaces. AB - Annexin self-association was studied with 90 degrees light scattering and resonance energy transfer between fluorescein (donor) and eosin (acceptor) labeled proteins. Synexin (annexin VII), p32 (annexin IV), and p67 (annexin VI) self-associated in a Ca(2+)-dependent manner in solution. However, this activity was quite labile and, especially for p32 and p67, was not consistently observed. When bound to chromaffin granule membranes, the three proteins consistently self associated and did so at Ca2+ levels (pCa 5.0-4.5) approximately 10-fold lower than required when in solution. Phospholipid vesicles containing phosphatidylserine and phosphatidylethanolamine (1:1 or 1:3) were less effective at supporting annexin polymerization than were those containing phosphatidylserine and phosphatidylcholine (1:0, 1:1, or 1:3). The annexins bound chromaffin granule membranes in a positively cooperative manner under conditions where annexin self-association was observed, and both phenomena were inhibited by trifluoperazine. Ca(2+)-dependent chromaffin granule membrane aggregation, induced by p32 or synexin, was associated with intermembrane annexin polymerization at Ca2+ levels less than pCa 4, but not at higher Ca2+ concentrations, suggesting that annexin self-association may be necessary for membrane contact at low Ca2+ levels but not at higher Ca2+ levels where the protein may bind two membranes as a monomer. PMID- 1911747 TI - The carboxyl modifier 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide (EDC) inhibits half of the high-affinity Mn-binding site in photosystem II membrane fragments. AB - The diphenylcarbazide(DPC)/Mn2+ assay [Hsu, B.-D., Lee, J.-Y., & Pan, R.-L. (1987) Biochim. Biophys. Acta 890, 89-96] was used to assess the amount of the high-affinity Mn-binding site in manganese-depleted photosystem II (PS II) membrane fragments from spinach and Scenedesmus obliquus. The assay mechanism at high DPC concentration was shown to involve noncompetitive inhibition of only half of the control level of DPC donation to PS II by micromolar concentrations of Mn at pH 6.5 (i.e., one of two DPC donation sites is inhibited). At low DPC concentration both DPC and Mn2+ donate to PS II additively. Treatment with the carboxyl amino acid modifier 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide (EDC) inhibited half of the high-affinity Mn-binding site in spinach and Scenedesmus WT PS II membranes and all of the available site in Scenedesmus LF-1 mutant PS II membranes. A similar EDC concentration dependence was observed in all cases. Addition of 2 mM MnCl2 to the 10 mM EDC modification buffer provided complete protection for the Mn-binding site from modification. This protection was specific for Mn2+; six other divalent cations were ineffective. We conclude that EDC modifies that half of the high-affinity Mn-binding site that is insensitive to the histidine modifier diethyl pyrocarbonate (DEPC) [Seibert, M., Tamura, N., & Inoue, Y. (1989) Biochim. Biophys. Acta 974, 185-191] and directly affects ligands that bind Mn. The effects of EDC and DEPC that influence the high affinity site are mutually exclusive and are specific to the lumenal side of the PS II membrane. Removal of the two more loosely bound of the four functional Mn from PS II membranes uncovers that part of the high-affinity site associated with carboxyl but not histidyl residues. We suggest that carboxyl residues on reaction center proteins are associated with half of the high-affinity Mn-binding site in PS II and are involved along with histidine residues in binding Mn functional in the O2-evolving process. PMID- 1911748 TI - Protease treatments of photosystem II membrane fragments reveal that there are four separate high-affinity Mn-binding sites. AB - The "high-affinity Mn-binding site" in Mn-depleted photosystem II (PS II) membrane fragments isolated from Scenedesmus obliquus was examined by using the diphenylcarbazide (DPC)/Mn2+ non-competitive inhibition assay [Preston, C., & Seibert, M. (1991) Biochemistry (preceding paper in this issue)]. Different proteases were used to degrade lumenal surface protein segments from these PS II membranes, and a total of four independent high-affinity Mn-binding sites (ligands) were identified. Carboxypeptidase A, subtilisin, and Staphylococcus aureus V8 protease each degrade one of two high-affinity Mn-binding sites sensitive to the histidine chemical modifier diethyl pyrocarbonate (DEPC). However, sequential treatment experiments indicate that subtilisin degrades a DEPC-sensitive Mn-binding site that is different from the one degraded by the other two proteases. Trypsin also was found to degrade one of the DEPC-sensitive Mn-binding sites (that degraded by carboxypeptidase A and V8 protease). In addition, trypsin degrades one of two 1-ethyl-3-[(3 dimethylamino)propyl]carbodiimide (EDC) sensitive Mn-binding sites, but only in the absence of the 30-kDa extrinsic protein. Thus, the 30-kDa extrinsic protein associated with O2 evolution appears to protect the EDC-sensitive binding site from trypsin degradation. No protease has yet been identified that will degrade the trypsin-insensitive EDC-sensitive Mn-binding site. Under the conditions of the assay (high DPC concentration), more than three Mn per reaction center were found bound to the membrane with a KM of about 0.4 microM, as determined by direct metal analysis. This is consistent with the idea that each of the four high-affinity sites binds (or provides a ligand for) one of four Mn.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1911749 TI - Kinetic properties of the acceptor quinone complex in Rhodopseudomonas viridis. AB - The kinetics of electron transfer from the primary (QA) to the secondary (QB) quinone acceptor in whole cells and chromatophores of Rhodopseudomonas viridis was studied as a function of the redox state of QB and of pH by using a photovoltage technique. Under conditions where QB was oxidized, the reoxidation of QA- was found to be essentially monophasic and independent of pH with a half time of about 20 microseconds. When QB was reduced to the semiquinone form by a preflash, the reoxidation of QA- was slowed down showing a half-time between 40 and 80 microseconds at pH less than or equal to 9. Above pH 9, the rate of the second electron transfer decreased nearly one order of magnitude per pH unit. After a further preflash, the fast and pH-independent kinetics of QA- reoxidation was essentially restored. The concentration of QA still reduced 100 microseconds after its complete reduction by a flash showed distinct binary oscillations as a function of the number of preflashes, confirming the interpretation that the electron-transfer rate depends on the redox state of QB. After addition of o phenanthroline, the reoxidation of QA- is slowed down to the time range of seconds as expected for a back-reaction with oxidized cytochrome. Under conditions where inhibitors of the electron transfer between the quinones fail to block this reaction in a fraction of the reaction centers due to the presence of the extremely stable and strongly bound semiquinone, QB-, these reaction centers show a slow electron transfer on the first flash and a fast one on the second, i.e., an out-of-phase oscillation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1911750 TI - Biochemical and kinetic characteristics of the interaction of the antitumor antibiotic sparsomycin with prokaryotic and eukaryotic ribosomes. AB - Using 125I-labeled phenol-alanine sparsomycin, an analogue of sparsomycin having higher biological activity than the unmodified antibiotic, we studied the requirements and the characteristics of its interaction with the ribosome. The drug does not bind to either isolated ribosomal subunits or reconstituted whole ribosomes. For sparsomycin binding to 70S and 80S ribosomes, the occupation of the peptidyltransferase P-site by an N-blocked aminoacyl-tRNA is a definitive requirement. The sparsomycin analogue binds to bacterial and yeast ribosomes with Ka values of around 10(6) M-1 and 0.6 x 10(6) M-1, respectively, but its affinity is probably affected by the character of the peptidyl-tRNA bound to the P-site. Chloramphenicol, lincomycin, and 16-atom ring macrolides compete with sparsomycin for binding to bacterial ribosomes, but streptogramins and 14-atom ring macrolides do not. Considering the reported low affinity of puromycin for bacterial ribosomes, this antibiotic is also a surprisingly good competitor of sparsomycin binding to these particles. In the case of yeast ribosomes, blasticidin is a relatively good competitor of sparsomycin interaction, but anisomycin, trichodermin, and narciclasin are not. As expected, puromycin is a poor competitor of the binding in this case. The results from competition studies carried out with different sparsomycin analogues reveal, in some cases, a discrepancy between the drug ribosomal affinity and its biological effects. This suggests that some intermediate step, perhaps a ribosomal conformational change, is required for the inhibition to take place. PMID- 1911751 TI - Motion of aromatic side chains, picosecond fluorescence, and internal energy transfer in Escherichia coli thioredoxin studied by site-directed mutagenesis, time-resolved fluorescence spectroscopy, and molecular dynamics simulations. AB - We have determined the picosecond fluorescence of the four aromatic amino acid residues (W28, W31, Y49, and Y70) in wild-type Escherichia coli thioredoxin (wt Trx) and a mutant Trx with W31 replaced by phenylalanine, Trx-W28-W31F. The internal motions of the four aromatic side chains were also analyzed. We examined the possibility of using internal energy transfer from tyrosine to tryptophan as a measure of long-range distances. The major features of the lifetime distribution of tryptophan fluorescence were unchanged in the W31F mutation, indicating that the environment of W28 is similar in both wt Trx and Trx-W28 W31F. However, the mutation of W31F changed the mobility of W28, situated close to the active-site disulfide/dithiol, but not the mobility of two tyrosines, Y49 and Y70, situated on the other side of the molecule. The mobility of the two tyrosine residues increased upon reduction of the active-site disulfide, indicating a looser structure with reduction. This increased motion could also be seen from molecular dynamics simulations. The change in energy transfer rates, as judged by tyrosine fluorescence lifetimes, was in agreement with energy transfer rates calculated from the molecular dynamics simulations. The anisotropy of tryptophan and tyrosine fluorescence could be separated in three parts: (I) overall rotation of the protein (10(-9)s), (II) internal mobility of side chains (10(-10)s), and (III) a very fast relaxation (10(-12)s). We can only experimentally detect this very fast relaxation when the internal motion is not present. PMID- 1911752 TI - Construction, purification, and characterization of a hybrid protein comprising the DNA binding domain of the LexA repressor and the Jun leucine zipper: a circular dichroism and mutagenesis study. AB - An increasing number of eukaryotic transcription factors interacting specifically with DNA comprise a dimerization motif called the "leucine zipper". These leucine zipper proteins form homodimers and/or heterodimers with another protein containing a leucine zipper motif. The leucine zipper of the oncoprotein Jun is particular in that Jun may form homodimers as well as heterodimers with the oncoprotein Fos, which are however more stable than the Jun-Jun homodimers. Leucine zipper dimerization is thought to occur through a coiled-coil arrangement of parallel alpha-helices, but the rules governing the specificity of homo- and/or heterodimerization are still largely unknown. To address this question in the case of the Jun leucine zipper, we constructed a fusion protein containing the amino-terminal DNA binding domain of the LexA repressor from Escherichia coli fused to the Jun leucine zipper. This hybrid protein (LexA-JunZip) is stable in E. coli and confers much tighter repression in vivo than the DNA binding domain of LexA alone. DNA binding competition experiments with synthetic Jun and Fos leucine zipper peptides in vitro showed that the leucine zipper mediated dimerization of LexA-JunZip is essential for DNA binding of the fusion protein. The purified LexA-JunZip protein dimerizes in vitro with a dimerization constant of 2 x 10(7) M-1 at 5 degrees C. Dimerization is very sensitive to temperature, since the dimerization constant drops at 20 degrees C to 2 x 10(6) M-1 and at 30 degrees C to only 3 x 10(5) M-1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1911753 TI - Optically detected triplet-state magnetic resonance studies of the DNA complexes of the bisquinoline analogue of echinomycin. AB - The polymeric DNA and model duplex oligonucleotide complexes of the bisquinoline analogue of echinomycin (2QN) have been studied by optical detection of triplet state magnetic resonance (ODMR) spectroscopy, with the quinoline chromophores of the drug used as intrinsic probes. Plots of ODMR transition frequencies versus monitored wavelength revealed heterogeneity in the phosphorescence emission of 2QN which was ascribed to the presence of a major and minor conformation of the drug in aqueous solutions (referred to as the red and blue forms of 2QN, respectively, in this report). ODMR results, in conjunction with findings from low-temperature phosphorescence investigations, indicate that the quinoline chromophores of the major (red) form of 2QN are involved in aromatic stacking interactions in complexes with the natural DNAs from Escherichia coli, Micrococcus lysodeikticus, Clostridium perfringens, and calf thymus as evidenced by red shifts in the phosphorescence 0,0-band of the drug, reductions in the phosphorescence lifetime and zero-field splitting (zfs) D and E parameters, and polarity reversals of the ODMR slow passage signals upon complex formation between the analogue and DNA. The polarity reversals, which reflect shifts in the triplet-state sublevel populations induced by complex formation, apparently result from changes in the triplet sublevel decay constants upon binding to the natural DNAs. The 2QN complexes of the double-stranded alternating copolymers poly(dG-dC).poly(dG-dC) [abbreviated as poly[d(G-C)2]] and poly(dA-dT).poly(dA dT) [abbreviated as poly(dA-dT).poly(dA-dT) [abbreviated as poly[d(A-T)2], the homopolymer duplexes poly(dG).poly(dC) [abbreviated as poly(dG.dC)] and poly(dA).poly(dT) [abbreviated as poly(dA.dT)], and the self-complementary oligonucleotides d(ACGT)2, d(TCGA)2, and d(ACGTACGT)2 were also investigated. The extent of reduction of the zfs D parameter (delta D) for the major form of 2QN upon complex formation with the polymeric DNAs was found to scale linearly with the standard free energy of the drug-DNA interaction (delta G degrees) calculated from previously reported binding studies for these targets [Fox, K. R., et al. (1980) Biochem. J. 191, 729-740]. This relationship between spectroscopic and thermodynamic properties of the 2QN-polynucleotide complexes is a consequence of the effects of base stacking interactions on the electronic states of the intercalator, which were postulated to arise from second-order shifts of the ground-state and the triplet-state energies of the complex on the basis of a modification of the solvent effect theory of van Egmond et al. [(1975) Chem. Phys. Lett. 34, 423-426]. PMID- 1911754 TI - Structure of Colorado potato beetle lipophorin: differential scanning calorimetric and small-angle X-ray scattering studies. AB - The structure of lipophorin, isolated from hemolymph of the Colorado potato beetle, was investigated by differential scanning calorimetry (DSC) and small angle X-ray scattering. The DSC heating curves of intact lipophorin showed endothermic peaks that were similar to peaks obtained with the hydrocarbon fraction isolated from this lipophorin. The observed peaks correlated with the transition of the hydrocarbons from an ordered into a more disordered state. Changes in structure of the lipophorin particles with increasing temperature were also observed by small-angle X-ray scattering studies. The structural organization of lipophorin was further elucidated by simulation analysis, using a three-layered symmetrical sphere as a model. These studies revealed that lipophorin from the Colorado potato beetle is a sphere with a maximum diameter of 175 A. The sphere is composed of three radially symmetrical layers of different electron densities. The outer layer (37.5-39.5 A in thickness) is composed of phospholipid, apolipophorin I, and part of apolipophorin II. The middle layer (5 10 A) contains diacylglycerol, the rest of apolipophorin II, and probably beta carotene. The core of the particle (40-45 A) only contains hydrocarbons. This structure differs from another model, previously proposed for cockroach and locust lipophorins [Katagiri, C., Sato, M., & Tanaka N. (1987) J. Biol. Chem. 262, 15857-15861], in the small size of the middle layer. The volume of the middle layer correlated well with the low diacylglycerol content of this lipophorin. PMID- 1911755 TI - Fourier transform infrared spectroscopic studies of Ca(2+)-binding proteins. AB - The secondary structures of calmodulin and parvalbumin are well established from X-ray diffraction and nuclear magnetic resonance spectroscopic studies, which indicate that these proteins are predominantly alpha-helical in character. Recent infrared studies have nevertheless suggested that the helical structures present in these proteins in solution are not the standard alpha-helix but rather some kind of distorted helices [Trewhella, J., et al. (1989) Biochemistry 28, 1294]. The evidence for this was the unusually low amide I frequency for calmodulin and troponin C in 2H2O solution. The studies presented here, however, suggest that the helical structures in these proteins are not significantly distorted, for two reasons. First, distorted helical structures have weaker hydrogen bonds than the standard alpha-helix and would therefore be expected to absorb at a higher rather than a lower frequency. Second, distorted helical structures would absorb at an unusual frequency in H2O solutions which is not the case for the proteins studied here. The band frequency of these proteins is observed to occur at a frequency observed with other proteins known to contain predominantly alpha-helical structures. Quantitative analysis of the FT-IR spectra of calmodulin (67% alpha helix) and parvalbumin (68% alpha-helix) in H2O in the presence of Ca2+ gives helical contents similar to those reported by X-ray studies. This raises the question as to why these proteins in H2O show a normal frequency for the presence of alpha-helical structures and an abnormal frequency in 2H2O. Addition of deuterated glycerol to the proteins in 2H2O solutions results in a significant shift of absorbance to higher frequency.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1911756 TI - Extracting hydrophobic free energies from experimental data: relationship to protein folding and theoretical models. AB - Solubility and vapor pressure measurements of hydrocarbons in water are generally thought to provide estimates of the strength of the hydrophobic effect in the range 20-30 cal/(mol.A2). Our reassessment of the solubility data on the basis of new developments in solution thermodynamics suggests that the hydrophobic surface free energy for hydrocarbon solutes is 46-47 cal/(mol.A2), although the actual value depends strongly on curvature effects [Nicholls et al. (1991) Proteins (in press); Sharp et al. (1991) Science 252, 106-109]. The arguments to support such a significant increase in the estimate of the hydrophobic effect stem partly from theoretical considerations and partly from the experimental results of De Young and Dill [(1990) J. Phys. Chem. 94, 801-809] on benzene partition between water and alkane solvents. Previous estimates of the hydrophobic effect derive from an analysis of solute partition data, which does not fully account for changes in volume entropy. We show here how the ideal gas equations, combined with experimental molar volumes, can account for such changes. Revised solubility scales for the 20 amino acids, based on cyclohexane to water and octanol to water transfer energies, are derived. The agreement between these scales, particularly the octanol scale, and mutant protein stability measurements from Kellis et al. [(1989) Biochemistry 28, 4914-4922] and Shortle et al. [(1990) Biochemistry 29, 8033-8041] is good. The increased strength of the hydrophobic interaction has implications for the energetics of protein folding, substrate binding, and nucleic acid base stacking and the interpretation of computer simulations. PMID- 1911757 TI - Primary structure of hydrogenase I from Clostridium pasteurianum. AB - Peptides obtained by cleavage of Clostridium pasteurianum hydrogenase I have been sequenced. The data allowed design of oligonucleotide probes which were used to clone a 2310-bp Sau3A fragment containing the hydrogenase encoding gene. The latter has been sequenced and was found to translate into a protein composed of 574 amino acids (Mr = 63,836), including 22 cysteines. C. pasteurianum hydrogenase is homologous to, but longer than, the large subunit of Desulfovibrio vulgaris (Hildenborough) [Fe] hydrogenase. It includes an additional N-terminal domain of ca. 110 amino acids which contains eight cysteine residues and which therefore could accommodate two of its postulated four [4Fe-4S] clusters. C. pasteurianum hydrogenase is most similar in length, cysteine positions, and sequence altogether to the translation product of a putative hydrogenase encoding gene from D. vulgaris (Hildenborough). Comparisons of the available [Fe] hydrogenase sequences show that these enzymes constitute a structurally rather homogeneous family. While they differ in the length of their N-termini and in the number of their [4Fe-4S] clusters, they are highly similar in their C-terminal halves, which are postulated to harbor the hydrogen-activating H cluster. Five conserved cysteine residues occurring in this domain are likely ligands of the H cluster. Possible ligation by other residues, and in particular by methionine, is discussed. The comparisons carried out here show that the H clusters most probably possess a common structural framework in all [Fe] hydrogenases. On the basis of the available data on these proteins and on the current developments in iron-sulfur chemistry, the H clusters possibly contain six to eight iron atoms.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1911758 TI - Comparison of the effects of saccharide binding and crystallization on the zinc transition-metal site of concanavalin A. AB - The Zn site in concanavalin A solution was studied by X-ray absorption fine structure spectroscopy (XAFS) with and without the saccharide methyl alpha-D glucoside (aMG) bound to the protein. No structural change occurs in the metal binding site when the saccharide is bound to the protein. There is, however, evidence for structural change remote from the metal site. This is in contrast to the significant changes that we have previously found to occur in the near neighborhood of the Zn atom when an aqueous solution of Zn concanavalin A crystallizes. We propose a structural explanation of these facts based on the known crystal structure of concanavalin A. PMID- 1911759 TI - Isolation and characterization of a novel endogenous inhibitor of the proteasome. AB - A novel endogenous inhibitor of the proteasome (high molecular weight multicatalytic protease) has been isolated and characterized from human erythrocytes. After purification by ion-exchange and sizing chromatography, the inhibitor displayed a native molecular mass of approximately 200 kDa and contained a single subunit of 50 kDa with an isoelectric point of 6.9. Although the inhibitor noncompetitively blocks proteolysis of [methyl-14C]-alpha-casein (Ki = 7.1 x 10(-8) M) and inhibits hydrolysis of Suc-Leu-Leu-Val-Tyr-AMC, it did not affect hydrolysis of other peptide substrates, such as MeOSuc-Phe-Leu-Phe-MNA and Z-Ala-Arg-Arg-MNA. To further characterize the 50-kDa inhibitor, a monoclonal antibody (MI-8) was generated that showed specific binding upon Western blot analysis of both native PAGE and SDS-PAGE. Immunoprecipitation with MI-8 specifically removed inhibitor activity against the proteasome. The 50-kDa inhibitor is distinct from a previously described 40-kDa inhibitor of the proteasome (Murakami, K., & Etlinger, J.D. (1986) Proc. Natl. Acad. Sci. U.S.A. 83, 7588-7592) on the basis of lack of cross-reactivity with MI-8 and dissimilar peptide digest patterns. It is suggested that these endogenous inhibitors may have a role in ATP/ubiquitin-dependent proteolysis and/or other cellular functions involving this protease. PMID- 1911760 TI - Identification of the catalytic nucleophile of tRNA (m5U54)methyltransferase. AB - A covalent complex between tRNA (m5U54)methyltransferase, 5-fluorouridine tRNA(Phe), and S-adenosyl-L-[methyl-3H]methionine was formed in vitro and purified. Previously, it was shown that in this complex the 6-position of fluorouridine-54 is covalently linked to a catalytic nucleophile and the 5 position is bound to the transferred methyl group of AdoMet [Santi, D. V., & Hardy, L. W. (1987) Biochemistry 26, 8599-8606]. Proteolysis of the complex generated a [3H]methyl-FUtRNA-bound peptide, which was purified by 7 M urea-15% polyacrylamide gel electrophoresis. The peptide component of the complex was sequenced by gas-phase Edman degradation and found to contain two cysteines. The tritium was shown to be associated with Cys 324 of the methyltransferase, which unequivocally identifies this residue as the catalytic nucleophile. PMID- 1911761 TI - Protein disulfide isomerase appears necessary to maintain the catalytically active structure of the microsomal triglyceride transfer protein. AB - Protein disulfide isomerase (PDI) is a component of the microsomal triglyceride transfer protein (MTP) complex. This study was initiated to help elucidate the role of PDI in MTP. The 88-kDa polypeptide of MTP (88K) was dissociated from PDI by using chaotropic agents (NaClO4 and KSCN), low concentrations of a denaturant (guanidine hydrochloride) or a nondenaturing detergent (octyl glucoside). As assessed by fluorescence and circular dichroism spectroscopy, these three different approaches appeared to dissociate the components of MTP under mild, nondenaturing conditions. The dissociating agents were diluted or removed by dialysis, and the free PDI and 88K were further characterized. In all cases, the dissociation coincided with the loss of triglyceride transfer activity. The free 88-kDa polypeptide readily aggregated, suggesting that it is a hydrophobic peptide. Even in the presence of chaotropic agents, when 88K was not aggregated, transfer activity was not expressed. These results suggest that the association of PDI with 88K is necessary to maintain the catalytically active form of the triglyceride transfer protein and prevent the aggregation of 88K. PMID- 1911762 TI - Study of a hammerhead ribozyme containing 2'-modified adenosine residues. AB - The improved synthesis of 2'-fluoro-2'-deoxyadenosine (2'-FA) starting from adenosine is described. This compound was converted to the phosphoramidite and incorporated into a hammerhead ribozyme RNA with the use of automated RNA synthesis techniques. Ribozymes containing 2'-deoxy-adenosine (2'-dA) were prepared in a similar manner. A kinetic rate comparison of the unmodified ribozyme with two ribozymes that had every adenosine replaced with 2'FA or 2'-dA revealed a large decrease in catalytic efficiency (kcat/Km) for the modified ribozymes resulting from a drop in kcat. The kinetic analysis of a number of partially substituted 2'-FA or 2'-dA containing hammerheads revealed that the decrease in activity was not associated with any particular residue but was the result of the accumulation of modified nucleosides within the structure. PMID- 1911763 TI - Mechanistic studies of a tyrosine-dependent catalytic antibody. AB - A pre-steady-state multiple-turnover kinetic burst is observed during hydrolysis of phenyl acetate by the catalytic antibody, 20G9. The burst is caused by partial product inhibition by phenol (Ki,app = 2.5 microM), which lowers both kcat and KM by almost an order of magnitude without affecting kcat/KM. The acid limb of the steady-state kcat pH profile of native 20G9 has a pKa of 9.6, suggesting a catalytic role for tyrosine. Additional evidence for an essential tyrosyl residue is that mild treatment of 20G9 with tetranitromethane nitrates a single tyrosine per equivalent of antigen binding sites and the mononitrated derivative has less than 5% of the native activity. Near-UV absorbance spectroscopy suggests that the alternative substrates N-carbobenzoxyglycine O-phenyl ester (ZG-OPh) and N acetylglycine O-phenyl ester (AcG-OPh) acylate multiple tyrosines on the antibody. Neither ZG-OPh nor AcG-OPh are measurably catalyzed once appreciable acylation has taken place. Antibody acylated by ZG-OPh is inactive toward phenyl acetate hydrolysis, but can be reactivated by hydroxylamine. The data and derived kinetic rate equations are consistent with an acyl mechanism for phenyl acetate hydrolysis in which phenol inhibits by binding to a covalent O-acetyltyrosyl intermediate, slowing deacylation. Although the data are consistent with such a mechanism, they do not rule out other plausible, yet less unifying mechanisms of phenol inhibition; the observed burst could conceivably result from partial mixed phenol inhibition or from phenol-induced nonproductive substrate binding. Because antibodies often use tyrosines in antigen binding, tyrosyl catalytic antibodies may be commonly encountered in the future. PMID- 1911764 TI - Sequence specificity in triple-helix formation: experimental and theoretical studies of the effect of mismatches on triplex stability. AB - The specificity of a homopyrimidine oligonucleotide binding to a homopurine homopyrimidine sequence on double-stranded DNA was investigated by both molecular modeling and thermal dissociation experiments. The presence of a single mismatched triplet at the center of the triplex was shown to destabilize the triple helix, leading to a lower melting temperature and a less favorable energy of interaction. A terminal mismatch was less destabilizing than a central mismatch. The extent of destabilization was shown to be dependent on the nature of the mismatch. Both single base-pair substitution and deletion in the duplex DNA target were investigated. When a homopurine stretch was interrupted by one thymine, guanine was the least destabilizing base on the third strand. However, G in the third strand did not discriminate between a C.G and an A.T base pair. If the stretch of purines was interrupted by a cytosine, the presence of pyrimidines (C or T) in the third strand yielded a less destabilizing effect than purines. This study shows that oligonucleotides forming triple helices can discriminate between duplex DNA sequences that differ by one base pair. It provides a basis for the choice of antigene oligonucleotide sequences targeted to selected sequences on duplex DNA. PMID- 1911765 TI - Thermodynamic characterization of daunomycin-DNA interactions: microcalorimetric measurements of daunomycin-DNA binding enthalpies. AB - We report the first direct determination of binding enthalpies for the complexation of monomeric daunomycin with a series of 10 polymeric DNA duplexes. These measurements were accomplished by using a recently developed stopped-flow microcalorimeter capable of detecting reaction heats on the microjoule level. This enhanced sensitivity allowed us to measure daunomycin-DNA binding enthalpies at monomeric drug concentrations (e.g., 10-20 microM), thereby precluding the need to correct for daunomycin self-association, as has been required in previous batch calorimetric studies [Remeta, D. P., Marky, L. A., & Breslauer, K. J. (1984) Abstracts of Pittsburgh Conference and Exposition on Analytical Chemistry and Applied Spectroscopy, 838a; Breslauer, K. J., Remeta, D. P., Chou, W. Y., Ferrante, R., Curry, J., Zaunczkowski, D., Snyder, J. G., & Marky, L. A. (1987) Proc. Natl. Acad. Sci. U.S.A. 84, 8922-8926]. We correct the published daunomycin DNA binding enthalpies measured by batch calorimetry at higher drug concentrations (e.g., 0.5-1.0 M) for the enthalpy contribution associated with the binding-induced disruption of drug aggregates. The requisite correction term was obtained from a van't Hoff analysis of temperature-dependent NMR measurements on daunomycin solutions. We find remarkable agreement between the net binding enthalpies derived from these corrected batch calorimetric data and the corresponding binding enthalpies measured directly by stopped-flow microcalorimetry. The enhanced sensitivity of the stopped-flow instrument also allowed us to evaluate the influence of drug binding density on the daunomycin DNA binding enthalpies. This assessment was accomplished by conducting stopped flow calorimetric measurements over a range of seven different drug-to-phosphate ratios (r). For most of the 10 DNA host duplexes studied, we find that the daunomycin binding enthalpies exhibit small but significant r dependencies. The sensitivity of the stopped-flow instrument also enabled us to detect significant dilution enthalpies for several of the drug-free DNA duplexes, a quantity generally assumed to be negligible in previous studies. We discuss the binding enthalpies, their dependence on binding density, and the duplex dilution enthalpies in terms of the influence of base composition, sequence, conformation/hydration, and binding cooperativity on the sign and the magnitudes of the daunomycin-DNA binding enthalpy data reported here. PMID- 1911766 TI - Differences in thermal stability between reduced and oxidized cytochrome b562 from Escherichia coli. AB - The thermal stabilities of ferri- and ferrocytochrome b562 were examined. Thermally induced spectral changes, monitored by absorption and second-derivative spectroscopies, followed the dissociation of the heme moiety and the increased solvation of tyrosine residue(s) located in close proximity to the heme binding site. All observed thermal transitions were independent of the rate of temperature increase (0.5-2 degrees C/min), and the denatured protein exhibited partial to near-complete reversibility upon return to ambient temperature. The extent of renaturation of cytochrome b562 is dependent on the amount of time the unfolded conformer is exposed to temperatures above the transition temperature, Tm. All thermally induced spectra changes fit a simple two-state model, and the thermal transition was assumed to be reversible. The thermal transition for ferrocytochrome b562 yielded Tm and van't Hoff enthalpy (delta HvH) values of 81.0 degrees C and 137 kcal/mol, respectively. In contrast, Tm and delta HvH values obtained for the ferricytochrome were 66.7 degrees C and 110 kcal/mol, respectively. The estimated increase in the stabilization free energy at the Tm of ferricytochrome b562 following the one-electron reduction to the ferrous form, where delta delta G = delta Tm delta Sm [delta Sm = 324 cal/(K.mol), delta Tm = 14.3 degrees C] [Becktel, W. J., & Schellman, J. A. (1987) Biopolymers 26, 1859 1877], is 4.6 kcal/mol. PMID- 1911767 TI - Mutations in the small subunit of ribulosebisphosphate carboxylase affect subunit binding and catalysis. AB - Fully functional Synechococcus PCC 6301 ribulose 1,5-bisphosphate carboxylase oxygenase (kcat = 11.8 s-1) was assembled in vitro following separate expression of the large- and small-subunit genes in different Escherichia coli cultures. The small subunits were expressed predominantly as monomers, in contrast to the large subunits which have been shown to be largely octameric when expressed separately [Andrews, T. J. (1988) J. Biol. Chem. 263, 12213-12219]. This separate expression system was applied to the study of mutations in the amino-terminal arm of the small subunit, which is one of the major sites of contact with the large subunit in the assembled hexadecamer. It enabled the effects of a mutation on the tightness of binding of the small subunit to the large-subunit octamer to be distinguished from the effects of the same mutation on catalysis carried out by the assembled complex when fully saturated with mutant small subunits. This important distinction cannot be made when both subunits are expressed together in the same cell. Substitutions of conserved amino acid residues at positions 14 (Ala, Val, Gly, or Asp instead of Thr) and 17 (Cys instead of Tyr), which make important contacts with conserved large-subunit residues, were introduced by site directed mutagenesis. All mutant small subunits were able to bind to large subunits and form active enzymes. A potential intersubunit hydrogen bond involving the Thr-14 hydroxyl group is shown to be unimportant. However, the binding of Gly-14, Asp-14, and Cys-17 mutant small subunits was weaker, and the resultant mutant enzymes had reduced catalytic rates compared to the wild type.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1911768 TI - Diastereotopic covalent binding of the natural inhibitor leupeptin to trypsin: detection of two interconverting hemiacetals by solution and solid-state NMR spectroscopy. AB - The naturally occurring peptidyl protease inhibitor leupeptin (N-acetyl-L-leucyl L-leucyl-L-argininal) has been prepared labeled with 13C at the argininal carbonyl. 13C chemical shift data for the trypsin-leupeptin inhibitor complex in the pH range 3.0-7.6 reveal the presence of two pH-dependent covalent complexes, suggestive of two interconverting diastereomers at the new asymmetric tetrahedral center created by covalent addition of Ser195 to either side of the 13C-enriched aldehyde of the inhibitor. At pH 7 two signals are observable at delta 98.8 and delta 97.2 (84:16 ratio), while at pH 3.0 the latter signal predominates. In the selective proton 13C-edited NOE spectrum of the major diastereomer at pH 7.4, a strong NOE is observed between the hemiacetal proton of the inhibitor and the C2 proton of His57 of the enzyme, thus defining the stereochemistry of the high pH complex to the S configuration in which the hemiacetal oxygen resides in the oxyanion hole. pH titration studies further indicate that the 13C chemical shift of the S diastereomer follows a titration curve with a pKa of 4.69, the magnitude of which is consistent with direct titration of the hemiacetal oxygen. Similar pH dependent chemical shifts were obtained by using CPMAS 13C NMR, providing evidence for the existence of the same diastereomeric equilibrium in the solid state. PMID- 1911769 TI - A monolayer and bulk study on the kinetic behavior of Pseudomonas glumae lipase using synthetic pseudoglycerides. AB - A heat-stable lipase from Pseudomonas glumae was purified to homogeneity. Its positional and stereospecific properties were investigated and compared with those of the well-known porcine pancreatic lipase. The kinetic properties of both enzymes were determined by use of six isomeric synthetic pseudoglycerides all composed of a single hydrolyzable fatty acyl ester bond and two lipase-resistant groups: one acylamino and one ether function. Two enzyme assay techniques were applied: a detergent-free system, the monomolecular surface film technique, and the pH-stat technique using clear micellar solutions of substrate in the presence of Triton X-100. Regarding the cleavage of primary ester bonds, P. glumae lipase possesses no stereopreference. In contrast, a large stereopreference in favor of the R-isomer is found for the hydrolysis of secondary ester bonds. Secondary ester bonds are efficiently cleaved by the lipase, which makes it of potential interest for enzymatic synthetic purposes. For the hydrolysis of this R-isomer a correlation between the experimental catalytic turnover rate and the binding constant for micelles was observed. The kinetic data of P. glumae lipase have been analyzed in terms of the scooting and hopping models for the action of lipolytic enzymes [Upreti, G.C., & Jain, M.K. (1980) J. Membr. Biol. 55, 113 121]. The results presented in this study are best explained by assuming that glumae lipase leaves the interface after a limited number of catalytic cycles. PMID- 1911770 TI - 1H, 15N, and 13C NMR signal assignments of IIIGlc, a signal-transducing protein of Escherichia coli, using three-dimensional triple-resonance techniques. AB - IIIGlc is an 18.1-kDa signal-transducing phosphocarrier protein of the phosphoenolpyruvate:glycose phosphotransferase system (PTS) of Escherichia coli. Virtually complete (98%) backbone 1H, 15N, and 13C nuclear magnetic resonance (NMR) signal assignments were determined by using a battery of triple-resonance three-dimensional (3D) NMR pulse sequences. In addition, nearly complete (1H, 95%; 13C, 85%) side-chain 1H and 13C signal assignments were obtained from an analysis of 3D 13C HCCH-COSY and HCCH-TOCSY spectra. These experiments rely almost exclusively upon one- and two-bond J couplings to transfer magnetization and to correlate proton and heteronuclear NMR signals. Hence, essentially complete signal assignments of this 168-residue protein were made without any assumptions regarding secondary structure and without the aid of a crystal structure, which is not yet available. Moreover, only three samples, one uniformly 15N-enriched, one uniformly 15N/13C-enriched, and one containing a few types of amino acids labeled with 15N and/or 13C, were needed to make the assignments. The backbone assignments together with the 3D 15N NOESY-HMQC and 13C NOESY-HMQC data have provided extensive information about the secondary structure of this protein [Pelton, J.G., Torchia, D.A., Meadow, N.D., Wong, C.-Y., & Roseman, S (1991) Proc. Natl. Acad. Sci. U.S.A. 88, 3479-3488]. The nearly complete set of backbone and side-chain atom assignments reported herein provide a basis for studies of the three-dimensional structure and dynamics of IIIGlc as well as its interactions with a variety of membrane and cytoplasmic proteins. PMID- 1911771 TI - Fourier transform infrared studies of secondary structure and orientation of pulmonary surfactant SP-C and its effect on the dynamic surface properties of phospholipids. AB - SP-C, a highly hydrophobic, 3.7-kDa protein constituent of lung surfactant, has been isolated from bovine lung lavage, purified, and reconstituted into binary lipid mixtures of 1,2-dipalmitoyl-phosphatidylcholine (DPPC) and 1,2 dipalmitoylphosphatidylglycerol (DPPG). Fourier transform infrared (FT-IR) spectroscopy has been applied to examine SP-C secondary structure, the average orientation of alpha-helical segments relative to the bilayer normal in membrane films, and the effect of protein on the thermotropic properties of the phospholipid acyl chains. In addition, dynamic surface measurements were made on phospholipid films at the A/W interface in the presence and absence of SP-C. SP-C (0.5 mol %) was found to possess about 60% alpha-helical secondary structure in lipid vesicles. Higher levels (1.5 mol %) of SP-C resulted in a slight increase of beta-forms, possibly resulting from protein aggregation. The helical segments exhibited an average angle of orientation of about 24 degrees with respect to the bilayer normal, suggesting a trans-bilayer orientation of the peptide. The observation that 70% of the peptide bond hydrogens are hard to exchange in D2O further reflects the hydrophobic nature of the molecule. SP-C produced little effect on the thermotropic properties of the binary lipid mixture, as measured from acyl chain C-H and C-D stretching frequencies. However, the presence of 1 mol % protein markedly reduced the viscance and increased the elasticity of surface films suggesting a mechanism by which SP-C facilitates the spreading of phospholipids on an aqueous surface. The possible physiological consequences of these observations are discussed. PMID- 1911772 TI - alpha-Mannosidase-catalyzed trimming of high-mannose glycans in noninfected and baculovirus-infected Spodoptera frugiperda cells (IPLB-SF-21AE). A possible contributing regulatory mechanism for assembly of complex-type oligosaccharides in infected cells. AB - Incubation of a Spodoptera frugiperda (IPLB-SF-21AE) cell extract with the oligosaccharide Man9GlcNAc2, the aglucosyl derivative of the glycan that is normally transferred from the dolichol carrier to the relevant Asn residue in the nascent protein, results in its trimming to Man6GlcNAc2, an intermediate that is relatively stable to further alpha-D-mannosidase action in these cells. On the other hand, incubation of a similar extract from cells that had been infected for various times with a wild-type baculovirus (Autographa californica nuclear polyhedrosis virus) or a recombinant baculovirus (r-BAC)/human plasminogen (HPg) construct employed for expression of HPg led to rapid trimming of Man6GlcNAc2 to Man5GlcNAc2 and Man3GlcNAc2. These latter reactions displayed temporal effects, in that an enhancement of this latter trimming process occurred as a function of the time of infection of the cells with the wild-type and recombinant viral constructs. We have previously demonstrated that the nature of the oligosaccharide assembled on Asn289 of HPg expressed in several lepidopteran insect cell lines was dependent on the time of infection of the cells with r BAC/HPg and that the amount of complex glycan found on this recombinant protein increased with an increase in infection times [Davidson, D. J., & Castellino, F. J. (1991) Biochemistry 30, 6167-6174].(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1911774 TI - Characterization of beta-apo-13-carotenone and beta-apo-14'-carotenal as enzymatic products of the excentric cleavage of beta-carotene. AB - Two new products from the incubation of beta-carotene with intestinal mucosa homogenates of human, monkey, ferret, and rat were isolated using high performance liquid chromatography (HPLC). Identification by comparing retention times in HPLC, by monitoring ultraviolet/visible spectra, by reduction to corresponding alcohol, by oxime formation, and by mass spectrometry demonstrated that they are beta-apo-13-carotenone and beta-apo-14'-carotenal. These compounds were not found in incubations done without intestinal homogenates or with disulfiram as an inhibitor. Under standard incubation conditions, these products increased linearly for 60 min and up to a protein concentration of 1.5 mg/mL and increased along with increasing concentrations of beta-carotene. Therefore, they are enzymatic cleavage products from beta-carotene. The formation of the beta-apo 13-carotenone and beta-apo-14'-carotenal provides direct evidence for an enzymatic excentric cleavage mechanism. PMID- 1911773 TI - Analysis of the interaction between charged side chains and the alpha-helix dipole using designed thermostable mutants of phage T4 lysozyme. AB - It was shown previously that the introduction of a negatively charged amino acid at the N-terminus of an alpha-helix could increase the thermostability of phage T4 lysozyme via an electrostatic interaction with the "helix dipole" [Nicholson, H., Becktel, W. J., & Matthews, B. W. (1988) Nature 336, 651-656]. The prior report focused on the two stabilizing substitutions Ser 38----Asp (S38D) and Asn 144----Asp (N144D). Two additional examples of stabilizing mutants, T109D and N116D, are presented here. Both show the pH-dependent increase in thermal stability expected for the interaction of an aspartic acid with an alpha-helix dipole. Control mutants were also constructed to further characterize the nature of the interaction with the alpha-helix dipole. High-resolution crystal structure analysis was used to determine the nature of the interaction of the substituted amino acids with the end of the alpha-helix in both the primary and the control mutants. Control mutant S38N has stability essentially the same as that of wild type lysozyme but hydrogen bonding similar to that of the stabilizing mutant S38D. This confirms that it is the electrostatic interaction between Asp 38 and the helix dipole, rather than a change in hydrogen-bonding geometry, that gives enhanced stability. Structural and thermodynamic analysis of mutant T109N provide a similar control for the stabilizing replacement T109D. In the case of mutant N116D, there was concern that the enhanced stability might be due to a favorable salt-bridge interaction between the introduced aspartate and Arg 119, rather than an interaction with the alpha-helix dipole. The additivity of the stabilities of N116D and R119M seen in the double mutant N116D/R119M indicates that favorable interactions are largely independent of residue 119. As a further control, Asp 92, a presumed helix-stabilizing residue in wild-type lysozyme, was replaced with Asn. This decreased the stability of the protein in the manner expected for the loss of a favorable helix dipole interaction. In total, five mutations have been identified that increase the thermostability of T4 lysozyme and appear to do so by favorable interactions with alpha-helix dipoles. As measured by the pH dependence of stability, the strength of the electrostatic interaction between the charged groups studied here and the helix dipole ranges from 0.6 to 1.3 kcal/mol in 150 mM KCl. In the case of mutants S38D and N144H, NMR titration was used to measure the pKa's of Asp 38 and His 144 in the folded structures.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1911775 TI - Structure of the propeptide of prothrombin containing the gamma-carboxylation recognition site determined by two-dimensional NMR spectroscopy. AB - The propeptides of the vitamin K dependent blood clotting and regulatory proteins contain a gamma-carboxylation recognition site that directs precursor forms of these proteins for posttranslational gamma-carboxylation. Peptides corresponding to the propeptide of prothrombin were synthesized and examined by circular dichroism (CD) and nuclear magnetic resonance spectroscopy (NMR). CD spectra indicate that these peptides have little or no secondary structure in aqueous solutions but that the addition of trifluoroethanol induces or stabilizes a structure containing alpha-helical character. The maximum helical content occurs at 35-40% trifluoroethanol. This trifluoroethanol-stabilized structure was solved by two-dimensional NMR spectroscopy. The NMR results demonstrate that residues 13 to -3 form an amphipathic alpha-helix. NMR spectra indicate that a similar structure is present at 5 degrees C, in the absence of trifluoroethanol. Of the residues previously implicated in defining the gamma-carboxylation recognition site, four residues (-18, -17, -16, and -15) are adjacent to the helical region and one residue (-10) is located within the helix. The potential role of the amphipathic alpha-helix in the gamma-carboxylation recognition site is discussed. PMID- 1911776 TI - Mechanistic studies on thrombin catalysis. AB - The kinetic mechanism of the cleavage of four p-nitroanilide (pNA) substrates by human alpha-thrombin has been investigated by using a number of steady-state kinetic techniques. Solvent isotope and viscosity effects were used to determine the stickiness of the substrates at the pH optimum of the reaction; a sticky substrate is defined as one that undergoes catalysis faster than it dissociates from the Michaelis complex. Whereas benzoyl-Arg-pNA could be classified as a nonsticky substrate, D-Phe-pipecolyl-Arg-pNA was very sticky. The other two substrates (tosyl-Gly-Pro-Arg-pNA and acetyl-D-Phe-pipecolyl-Arg-pNA) were slightly sticky. The pH profiles of kcat/Km were bell-shaped for all substrates. The pKa values determined from the pH dependence of kcat/Km for benzoyl-Arg-pNA were about 7.5 and 9.1. Similar pKa values were determined from the pH profiles of kcat/Km for tosyl-Gly-Pro-Arg-pNA and acetyl-D-Phe-pipecolyl-Arg-pNA and for the binding of the competitive inhibitor N alpha-dansyl-L-arginine-4 methylpiperidine amide. The groups responsible for the observed pKa values were proposed to be His57 and the alpha-amino group of Ile16. The temperature dependence of the pKa values was consistent with this assignment. The pKa values of 6.7 and 8.6 observed in the pH profile of kcat/Km for D-Phe-pipecolyl-Arg-pNA were displaced to lower values than those observed for the other substrates. The displacement of the acidic pKa value could be attributed to the stickiness of this substrate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1911777 TI - Role of interactions involving C-terminal nonpolar residues of hirudin in the formation of the thrombin-hirudin complex. AB - The role of interactions involving C-terminal nonpolar residues of hirudin in the formation of the thrombin-hirudin complex has been investigated by site-directed mutagenesis. The residues Phe56, Pro60, and Tyr63 of hirudin were replaced by a number of different amino acids, and the kinetics of the inhibition of thrombin by the mutant proteins were determined. Phe56 could be replaced by aromatic amino acids without significant loss in binding energy. While substitution of Phe56 by alanine decreased the binding energy (delta G degrees b by only 1.9 kJ mol-1, replacement of this residue by amino acids with branched side chains caused larger decreases in delta G degrees b. For example, the mutant Phe56----Val displayed a decrease in delta G degrees b of 10.5 kJ mol-1. Substitution of Pro60 by alanine or glycine resulted in a decrease in delta G degrees b of about 6 kJ mol-1. Tyr63 could be replaced by phenylalanine without any loss in binding energy, and replacement of this residue by alanine caused a decrease of 2.2 kJ mol-1 in delta G degrees b. Substitution of Tyr63 by residues with branched side chains resulted in smaller decreases in delta G degrees b than those seen with the corresponding substitutions of Phe56; for example, the mutant Tyr63----Val showed a decrease in binding energy of 5.1 kJ mol-1. The effects of the mutations are discussed in terms of the crystal structure of the thrombin-hirudin complex. PMID- 1911778 TI - In vitro interaction of a polypeptide homologous to human Ro/SS-A antigen (calreticulin) with a highly conserved amino acid sequence in the cytoplasmic domain of integrin alpha subunits. AB - We endeavored to identify proteins interacting with KLGFFKR, a highly conserved motif in the cytoplasmic domain adjacent to the transmembrane domain of the alpha subunit of integrins. We found that affinity chromatography of cell extracts with this peptide followed by elution with EDTA resulted in the isolation of a 60-kDa protein (p60). The N-terminal amino acid sequence of this 60-kDa polypeptide was found to be highly homologous to the Ro/SS-A antigen, a 60-kDa protein homologous to calreticulin and Aplysia "memory molecule". The binding of p60 was found to be specific for the KLGFFKR sequence since this polypeptide did not bind to a peptide with a scrambled amino acid sequence (KLRFGFK), and it was also specifically eluted from the KLGFFKR affinity matrix ith soluble KLGFFKR peptide but not with the scrambled peptide. Solid phase in vitro binding assays demonstrated specific interaction of p60 with integrin alpha 3 and alpha 5 subunits but not with the beta 1 subunit. Furthermore, p60 could be copurified with alpha 3 beta 1 following coincubation in vitro. These interactions could be inhibited by KLGFFKR peptide and also by EDTA, indicating sequence-specific and divalent cation dependent binding. Despite the fact that calreticulin is thought to be localized in the endoplasmic reticulum, a pool of Ro/SS A antigen homologous 60-kDa polypeptide was found to be present in the soluble cytoplasm, indicating the feasibility of an interaction of p60 with the integrin alpha subunits. Our data suggest that p60 (Ro/SS-A Ag) can specifically bind to integrin alpha subunits via the highly conserved KLGFFKR amino acid sequence. PMID- 1911779 TI - Effects of proline mutations on the unfolding and refolding of human lysozyme: the slow refolding kinetic phase does not result from proline cis-trans isomerization. AB - The unfolding and refolding kinetics of six proline mutants of the human lysozyme (h-lysozyme) were carried out and compared to that of the wild-type protein. Our results show that the slow refolding phase observed in the h-lysozyme refolding kinetics cannot be ascribed to proline isomerization reactions. The h-lysozyme contains two proline residues at positions 71 and 103, both in the trans conformation in the native state. The refolding kinetics of the P71G/P103G mutant, in which both prolines have been replaced by a glycine, were found to be similar to those of the wild-type protein. The same slow phase amplitude of about 10% was found for both proteins, and the slow phase rate constants were also identical within experimental error. Other mutants such as P103G or P71G, in which only one of the two prolines has been replaced by a glycine, and A47P with its three prolines, gave identical slow refolding phases. The X-ray structure analysis and scanning microcalorimetric study of each protein (Herning et al., unpublished experiments) have confirmed that none of the considered mutations affects significantly protein structure and that no major changes in protein stability were brought about by these mutations. Therefore, comparison of the properties of the mutant and wild-type proteins is legitimate. Interestingly, the refolding kinetics of the V110P mutant, in which a proline residue has been introduced at position 110 (N-terminus of an alpha-helix), were clearly triphasic. For this mutant an additional very slow phase with properties similar to those expected from the proline hypothesis was detected. Equilibrium denaturation studies were conducted for each protein, and the refolding pathway of h-lysozyme is partly presented. We also discuss the effect of proline mutations on the energetics of the folding pathway of the h-lysozyme in water. PMID- 1911780 TI - Evidence for complex formation between rabbit lung flavin-containing monooxygenase and calreticulin. AB - Rabbit lung flavin-containing monooxygenase (FMO, EC 1.14.13.8) was denatured, reduced, carboxymethylated, digested with endoproteinase Glu-C or trypsin, and subjected to mass spectrometric analysis. The amino acid sequences of selected peptides were determined by tandem mass spectrometry. Over 90% of rabbit lung FMO was mapped by liquid secondary ion mass spectrometry (LSIMS). The FMO N-terminal amino acid was found to be N-acetylated, and the N-terminal 23 amino acid peptide contained an FAD binding domain consisting of Gly-X-Gly-X-X-Gly. Another peptide was found to contain a NADP+ binding domain consisting of Gly-X-Gly-X-X-Ala. The mapped and/or sequenced peptides were found to be completely consistent with the peptide sequence deduced from the cDNA data and the previously published gas phase sequencing data. Further mass spectrometry and protein analytical work unambiguously showed that rabbit lung FMO existed in tight association with a calcium-binding protein, calreticulin. Over 68% of rabbit lung calreticulin was mapped by LSIMS. Tandem mass spectrometric and gas-phase sequencing studies provided direct evidence for the identification of the N-terminal and other rabbit lung calreticulin-derived peptide sequences that were identical to other previously reported calreticulins. The complexation of calreticulin to rabbit lung FMO could account for some of the unusual physical properties of this FMO enzyme form. PMID- 1911781 TI - Primary structure of the assimilatory-type sulfite reductase from Desulfovibrio vulgaris (Hildenborough): cloning and nucleotide sequence of the reductase gene. AB - The nucleotide sequence encoding the structural gene (651 bp) and flanking regions for the assimilatory-type sulfite reductase from the sulfate-reducing bacterium Desulfovibrio vulgaris (Hildenborough) was determined after cloning a 1.4 kb HindIII/SalI genomic fragment possessing the gene into Bluescript pBS(+)KS. The primary structure of the protein was deduced, and the molecular mass of the apoprotein was estimated as 24 kDa. The amino acid sequence of the polypeptide shows some similarities at putative [Fe4S4] cluster binding sites in comparison with the heme protein subunit of the larger Escherichia coli and Salmonella typhimurium sulfite reductases and spinach nitrite reductase. This is the first reported sequence of a member of a new class of low molecular weight assimilatory sulfite-reducing enzymes recently identified in a number of anaerobic bacteria [Moura, I., Lina, A. R., Moura, J. J. G., Xavier, A. V., Fauque, G., Peck, H. D., & Le Gall, J. (1986) Biochem. Biophys. Res. Commun. 141, 1032-1041]. PMID- 1911782 TI - Hydrogen exchange in thermally denatured ribonuclease A. AB - Hydrogen exchange has been used to test for the presence of nonrandom structure in thermally denatured ribonuclease A (RNase A). Quenched-flow methods and 2D 1H NMR spectroscopy were used to measure exchange rates for 36 backbone amide protons (NHs) at 65 degrees C and at pH* (uncorrected pH measured in D2O) values ranging from 1.5 to 3.8. The results show that exchange is approximately that predicted for a disordered polypeptide [Molday, R. S., Englander, S. W., & Kallen, R. G. (1972) Biochemistry 11, 150-158]; we thus are unable to detect any stable hydrogen-bonded structure in thermally denatured RNase A. Two observations suggest, however, that the predicted rates should be viewed with some caution. First, we discovered that one of the approximations made by Molday et al. (1972), that exchange for valine NHs is similar to that for alanine NHs, had to be modified; the exchange rates for valine NHs are about 4-fold slower. Second, the pH minima for exchange tend to fall at lower pH values than predicted, by as much as 0.45 pH units. These results are in accord with those of Roder and co-workers for bovine pancreatic trypsin inhibitor [see Table I in Roder, H., Wagner, G., & Wuthrich, K. (1985) Biochemistry 24, 7407-7411]. The origin of the disagreement between predicted and observed pH minima is unknown but may be the high net positive charge on these proteins at low pH. In common with some other thermally unfolded proteins, heat-denatured ribonuclease A shows a significant circular dichroism spectrum in the far-ultraviolet region [Labhardt, A. M. (1982) J. Mol. Biol. 157, 331-355].(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1911783 TI - DNA triplex formation of oligonucleotide analogues consisting of linker groups and octamer segments that have opposite sugar-phosphate backbone polarities. AB - The DNA oligomer analogues 3'd(CTTTCTTT)5'-P4-5'd(TTCTTCTT)3' (IV), 5'd (TTTCTTTC)3'-P2-3'd(CTTTCTTT)5' (V), and 5'd(TTTCTTTC)3'-P2-3'd(CTTTCTTT)5'-P4 5'd-(TTCTTCTT)3' (VI) (P2 = P*P and P4 = P*P*P*P, where P = phosphate and * = 1,3 propanediol) have been synthesized. These oligomers consist of a linker group or groups and homopyrimidine oligonucleotides which have opposite sugar-phosphate backbone polarities. These oligomer analogues are designed to form triplexes with a duplex, 5'd(AAAGAAAGCCCTTTCTTTAAGAAGAA)3'.5'd(TTCTTCTTAAA- GAAAGGGCTTTCTTT)3' (I), which contains small homopurine clusters alternately located in both strands. The length of the linker groups, P2 and P4, was based upon a computer modeling analysis. Triplex formation by the unlinked octamers 5'd(TTCTTCTT)3' (II) and 5'd(TTTCTTTC)3' (III) and the linked oligomer analogues IV-VI with the target duplex was studied by thermal denaturation at pH 5.2. The order of stabilities of triplex formation by these oligomers was I-V much much greater than I-IV greater than I-(II, III). The mixture of I and VI showed two transitions corresponding to the dissociation of the third strand. The higher transition corresponded to the dissociation of 3'-3'-linked octamer segments, and the lower one corresponded to the dissociation of 5'-5'-linked octamer segments. The Tm of the latter transition was higher than that of the I-IV triplex; thus the triplex formed by the 5'-5'-linked octamer segment was stabilized by the triplex formed by the 3'-3'-linked octamer segments in the I-VI triplex. Triplex formation of this system was also studied in the presence of ethidium bromide.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1911784 TI - Molecular structure of a DNA decamber containing an anticancer nucleoside arabinosylcytosine: conformational perturbation by arabinosylcytosine in B-DNA. AB - Arabinosylcytosine (araC) is an important anticancer drug that has been shown to be misincorporated into DNA double helix. The incorporation of araC into DNA may have significant conformational consequences that could affect the function of DNA. In this paper, we present the high-resolution 3D structure of an araC containing decamer d[CCAGGC(araC)TGG], as determined by X-ray diffraction analysis, and assess the possible DNA structural perturbation induced by araC. The modified decamer was crystallized in the monoclinic C2 (a = 31.97 A, b = 25.56 A, c = 34.62 A and beta = 114.50 degrees) space group, the same as that from d(CCAGGCCTGG) [Heinemann, U., & Alings, C. (1989) J. Mol. Biol. 210, 369]. The structure of the araC-containing decamer was solved by the molecular replacement method and refined by the constrained least-squares refinement procedure to obtain a final R factor of 0.187 using 2349 [greater than 2.0 sigma(F)] observed reflections to a resolution of 1.6 A. The overall conformation resembles that of the canonical decamer DNA structure, but with significant differences in regions close to the araC site. The O2' hydroxyl groups of the araC residues lie in the major groove of the helix, and they are in close contact with the C5 methyl and C6 H6 atoms of the thymine on the 3'-side. This creates a higher buckle in the araC7-G14 base pair (14 degrees), as compared to that found in the canonical decamer (9 degrees). This may slightly destabilize B-DNA. No direct intramolecular hydrogen bond is formed, in contrast to the situation when araC is incorporated into Z-DNA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1911785 TI - Characterization of conformational features of DNA heteroduplexes containing aldehydic abasic sites. AB - The DNA duplexes shown below, with D indicating deoxyribose aldehyde absic sites and numbering from 5' to 3', have been investigated by NMR. The 31P and 31P-1H correlation data indicate [formula: see text] that the backbones of these duplex DNAs are regular. One- and two-dimensional 1H NMR data indicate that the duplexes are right-handed and B-form. Conformational changes due to the presence of the abasic site extend to the two base pairs adjacent to the lesion site with the local conformation of the DNA being dependent on whether the abasic site is in the alpha or beta configuration. The aromatic base of residue A17 in the position opposite the abasic site is predominantly stacked in the helix as is G17 in the analogous sample. Imino lifetimes of the AT base pairs are much longer in samples with an abasic site than in those containing a Watson-Crick base pair. The conformational and dynamical properties of the duplex DNAs containing the naturally occurring aldehyde abasic site are different from those of duplex DNAs containing a variety of analogues of the abasic site. PMID- 1911786 TI - Receptor-modulated iron release from transferrin: differential effects on N- and C-terminal sites. AB - Iron release to PPi from N- and C-terminal monoferric transferrins and their complexes with transferrin receptor has been studied at pH 7.4 and 5.6 in 0.05 M HEPES or MES/0.1 M NaCl/0.01 M CHAPS at 25 degrees C. The two sites exhibit kinetic heterogeneity in releasing iron. The N-terminal form is slightly less labile than its C-terminal counterpart at pH 7.4, but much more facile in releasing iron at pH 5.6. At pH 7.4, iron removal by 0.05 M pyrophosphate from each form of monoferric transferrin complexed to the receptor is considerably slower than from the corresponding free monoferric transferrin. However, at pH 5.6, complexation of transferrin to its receptor affects the two forms differently. The rate of iron release to 0.005 M pyrophosphate by the N-terminal species is substantially the same whether transferrin is free or bound to the receptor. In contrast, the C-terminal form releases iron much faster when complexed to the receptor than when free. Urea/PAGE analysis of iron removal from free and receptor-complexed diferric transferrin at pH 5.6 reveals that its C terminal site is also more labile in the complex, but its N-terminal site is more labile in free diferric transferrin. Thus, the newly discovered role of transferrin receptor in modulating iron release from transferrin predominantly involves the C-terminal site. This observation helps explain the prevalence of circulating N-terminal monoferric transferrin in the human circulation. PMID- 1911787 TI - Nucleotide-induced changes in the interaction of myosin subfragment 1 with actin: detection by antibodies against the N-terminal segment of actin. AB - The binding of myosin subfragment 1 (S-1) to actin in the presence and absence of nucleotides was determined under conditions of partial saturation of actin, up to 80%, by Fab(1-7), the antibodies against the first seven N-terminal residues on actin. In the absence of nucleotides, the binding constant of S-1 to actin (2 x 10(7) M-1) was decreased by 1 order of magnitude by Fab(1-7). The binding of S-1 to actin caused only limited displacement of Fab, and between 30 and 50% of actin appeared to bind both proteins. In the presence of MgAMP.PNP, MgADP, and MgPPi and at low S-1 concentrations, the same antibodies caused a large decrease in the binding of S-1 to actin. However, the binding of S-1.nucleotide to actin in the presence of Fab(1-7) increased cooperatively with the increase in S-1 concentration. Also, in contrast to rigor conditions, there was no indication for the binding of Fab(1-7) and S-1.nucleotide to the same actin molecules. These results show a nucleotide-induced transition in the actomyosin interface, most likely related to the different roles of the N-terminal segment of actin in the binding of S-1 and S-1.nucleotide. The possible implications of these findings to the regulation of actomyosin interactions are discussed. PMID- 1911788 TI - A comparative study of the interactions of synthetic peptides of the skeletal and cardiac troponin I inhibitory region with skeletal and cardiac troponin C. AB - The cardiac and skeletal TnI inhibitory regions have identical sequences except at position 110 which contains Pro in the skeletal sequence and Thr in the cardiac sequence. The effect of the synthetic TnI inhibitory peptides [skeletal TnI peptide (104-115), cardiac TnI peptide (137-148), and a single Gly substituted analogue at position 110] on the secondary structure of skeletal and cardiac TnC was investigated. The biphasic increases in ellipticity and tyrosine fluorescence were analyzed to determine the Ca2+ binding constants for the high- and low-affinity Ca2+ binding sites of TnC. Importantly, the skeletal and cardiac TnI peptides altered Ca2+ binding at the low-affinity sites of TnC, but the magnitude and direction of the pCa shifts depended on whether the peptides were bound to skeletal or cardiac TnC. For example, binding of skeletal TnI peptide to skeletal TnC (monitored by CD) caused a pCa shift of +0.30 unit such that a lower Ca2+ concentration was required to fill sites I and II, while binding of this peptide to cardiac TnC caused a pCa shift of -0.35 unit such that a higher Ca2+ concentration was required to fill site II. This is the first report of the alteration at the low-affinity regulatory sites (located in the N-terminal domain) by the skeletal TnI inhibitory peptide, even though the primary peptide binding site is located in the C-terminal domain of TnC, a finding which strongly indicates that there is communication between the two halves of the TnC molecule.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1911789 TI - 6,7-Diepicastanospermine, a tetrahydroxyindolizidine alkaloid inhibitor of amyloglucosidase. AB - A tetrahydroxyindolizidine alkaloid, 6,7-diepicastanospermine, was isolated from the seeds of Castanospermum australe by extraction with methanol and purified to homogeneity using ion-exchange, preparative thin-layer, and radial chromatography. A very low yield of a pyrrolidine alkaloid, N-(hydroxyethyl)-2 (hydroxymethyl)-3-hydroxypyrrolidine, was also obtained by analogous methods. The purity of both alkaloids was established by gas chromatography of their trimethylsilyl (TMS) derivatives as better than 99%. The molecular weight of each alkaloid was established as 189 and 161, respectively, by mass spectrometry, and the structure of each was deduced from their 1H and 13C NMR spectra. The structure of the pyrrolidine alkaloid is suggestive of a possible biosynthetic route to the polyhydroxyindolizidine and polyhydroxypyrrolizidine alkaloids which co-occur in C. australe. 6,7-Diepicastanospermine was found to be a moderately good inhibitor of the fungal alpha-glucosidase, amyloglucosidase (Ki = 8.4 x 10( 5) M) and a relatively weak inhibitor of beta-glucosidase. It failed to inhibit alpha- or beta-galactosidase, alpha- or beta-mannosidase, or alpha-L-fucosidase. Comparison of its inhibitory activity toward amyloglucosidase with those of its isomers, castanospermine and 6-epicastanospermine, demonstrated that epimerization of a single hydroxyl group can produce significant alteration of such inhibitory properties. PMID- 1911790 TI - 9-(5',6'-dideoxy-beta-D-ribo-hex-5'-ynofuranosyl)adenine, a novel irreversible inhibitor of S-adenosylhomocysteine hydrolase. AB - The acetylenic analogue of adenosine 9-(5',6'-dideoxy-beta-D-ribo-hex-5' ynofuranosyl)adenine has been synthesized, and its behavior as an inhibitor of bovine S-adenosylhomocysteine hydrolase has been examined. Incubation of the enzyme with excess inhibitor caused a time-dependent, irreversible inactivation of the enzyme that was accompanied by the reduction of two equivalents of NAD+ to NADH and the loss of the two remaining equivalents of NAD+. With use of radiolabeled inhibitor, it was established that 4 equiv of the acetylenic analog bind irreversibly to the enzyme and that 4 equiv were required to inactivate the enzyme completely. The inactivated enzyme could not be reactivated by incubation with NAD+. Denaturation studies revealed that 2 equiv of the inhibitor are bound more tightly to the enzyme than the remainder, suggesting the formation of a covalent linkage between the oxidized inhibitor and the enzyme. The putative covalent linkage was found to be acid sensitive but stable to mild base. The linkage could not be stabilized by treatment of the enzyme-inhibitor complex with either borohydride or cyanoborohydride. A Kl of 173 nM was measured for the inhibitor, making it one of the more potent inhibitors that have been reported. The enzyme used in these studies was isolated by modification of an affinity chromatography method reported by Narayanan and Borchardt [(1988) Biochim. Biophys. Acta 965, 22-28]. The affinity chromatography unexpectedly led to the isolation of two forms of the enzyme. The major form contained 4.0 mol of nucleotide cofactor/mol of enzyme tetramer, while the minor form carried only 2.0 mol/tetramer. PMID- 1911791 TI - The Registry of the International Society for Heart and Lung Transplantation: eighth official report--1991. AB - Less than 25 years since the first human-human heart transplantation, the worldwide experience exceeds 16,000 heart and 1600 lung transplantations from more than 200 centers. Excellent results in heart transplantation have been achieved in a wide variety of patients. During the past few years, lung transplantation has come of age. The specific indications for each technique continue to evolve. Although much progress has been made, it is hoped that future developments in immunosuppression will solve the problems of chronic rejection and decrease the risk of infections. On behalf of the Society, we would like to take this opportunity to sincerely thank each of the participants throughout the world who took the time and care to submit their data to the Registry. Through this compilation of the world's experience, the state of the art in thoracic transplantation may be shared with the transplant community. The extensive Registry data base will permit risk assessment of thoracic transplant recipients while avoiding the problems associated with small sample sizes. Each participant's continued diligence in providing follow-up reports on all recipients is essential for an accurate evaluation of the long-term prognosis of heart and lung transplantation. PMID- 1911792 TI - Pregnancy in heart transplant recipients: a good idea? PMID- 1911793 TI - Adenine nucleotide content in cold preserved human donor hearts and subsequent cardiac performance after orthotopic heart transplantation. AB - Myocardial high-energy phosphate content has been used as a parameter to evaluate the adequacy of donor organ preservation. The purpose of this study was to assess current techniques of preservation by measuring high-energy phosphates in cold preserved (4 degrees C) human donor hearts. Endomyocardial biopsy samples of the donor heart right ventricular septum (n = 24) were compared with samples from patients with normal cardiac function evaluated before chemotherapy (n = 12). Left ventricular and right ventricular ejection fractions were measured by means of radionuclide angiography early (24 to 72 hours) and late (mean 42 days) postoperatively. Mean total cold ischemic time was 146 +/- 54 minutes (range, 89 to 340 minutes). ATP nmol/mg noncollagenous protein in donor hearts was 38.2 +/- 10.7 and 31.9 +/- 13.6 (p = NS) in normal hearts. Early postoperative left ventricular and right ventricular ejection fraction was 55% +/- 14% and 40% +/- 9%, respectively. Late postoperative left ventricular and right ventricular ejection fraction was 64% +/- 14% and 50% +/- 10%, respectively; both represent significant increases in right and left ventricular ejection fraction (p less than 0.05). No correlation was found between ischemic time and donor ATP, ischemic time and ejection fraction, or ejection fraction and ATP. Three patients with normal donor heart ATP content had severe, but reversible, early graft dysfunction. In summary, currently used human donor heart preservation techniques are associated with normal values of high-energy phosphates and usually excellent early and late postoperative graft function.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1911794 TI - Preservation techniques for heart transplantation: comparison of hypothermic storage and hypothermic perfusion. AB - Preservation of the donor heart is an important and controversial subject in heart transplantation. This study compares simple hypothermic storage and hypothermic perfusion in a swine model of heart transplantation (n = 14). The donor hearts of group A (n = 7) were placed in simple hypothermic storage for 5 hours. The donor hearts of group B (n = 7) were placed onto a perfusion apparatus for 5 hours, with pressure maintained at 28 cm of H2O and a myocardial temperature of 8 to 10 degrees C. In both groups the hearts were initially protected with isosmolar potassium cardioplegic solution. The perfusate in group B contained moderate sodium, mannitol, glucose, insulin, and oxygen. The ischemic interval within both groups was 6 hours including orthotopic transplantation. Investigation was conducted at three time periods: prepreservation, postpreservation, and immediately after loading. For both groups there was nonsignificant depression of myocardial function (cardiac index, stroke index, stroke work index, ejection fraction, and wall stress) at the postpreservation period. After volume loading, for the hypothermic perfusion group there was significant improvement of myocardial function (cardiac index, p less than 0.01; stroke index, p less than 0.01) with no significant change in heart rate, systemic vascular resistance, and systolic blood pressure. There was also significant improvement in myocardial performance (p less than 0.05) for the hypothermic perfusion group after volume loading. Ultrastructural changes were minimal for both groups, and there were no major heart transplantation after 6 hours of ischemia; however, hearts retain their contractile capacity better after hypothermic perfusion than after simple hypothermic storage.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1911795 TI - Analysis of myocardial function in orthotopic cardiac allografts after prolonged storage in UW solution. AB - The need for a better organ preservative solution in heart transplantation is clear. At the same time, newer techniques in the assessment of cardiac function in the laboratory have made accurate load-independent quantification of myocardial preservation possible. Therefore a study was undertaken to evaluate left ventricular function in transplanted hearts after 14 hours of preservation in the intracellular lactobionate solution. Nine dogs were instrumented with ultrasonic dimension transducers, to measure left ventricular epicardial volume, and with micromanometers, to measure left ventricular pressure. Left ventricular wall volumes were determined from epicardial echocardiograms. To define the extent of organ injury resulting from the transplant procedure and cardiopulmonary bypass alone, four other animals were instrumented in a similar fashion, and left ventricular function was assessed after standard cardioplegic arrest and transplantation. The transplant procedures were performed with a warm ischemic period of 0.75 +/- 0.2 hours. In all experiments, data were collected before graft harvest and 1 hour after separation from cardiopulmonary bypass. Standard cardioplegic arrest and 2.4 +/- 0.1 hours of ischemia resulted in a decrease in left ventricular ejection fraction from 0.43 +/- 0.04 to 0.27 +/- 0.1 (37%) (p less than 0.01), a decrease in the slope of the stroke work/end diastolic volume relationship from 15.4 +/- 7.9 to 7.9 +/- 2.0 erg X 10(4) (49%; p less than 0.01), and a decrease in the myocardial power output from 19.7 +/- 10.9 to 5.9 +/- 1.9 (70%; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1911796 TI - Functional recovery of hearts after cardioplegia and storage in University of Wisconsin and in St. Thomas' Hospital solutions. AB - There are conflicting reports of the beneficial effects of University of Wisconsin (UW) cardioplegic solution used in heart preservation techniques. Therefore we investigated the efficacy of myocardial protection in adult rat hearts subjected to single-dose infusion (3 minutes) of nonoxygenated cardioplegic solutions (UW or St. Thomas' Hospital solution No. 2 [STH]) and stored at 4 degrees C by immersion in the same solution or in saline solution. Isolated working-heart preparations (n = 8 per group) were used to assess the prearrest (20 minutes' normothermic perfusion) and postischemic left ventricular functions. Four groups of hearts underwent 5, 8, 10, and 20 hours of cold ischemia (4 degrees C) in UW solution. Hearts stored for 8 to 20 hours showed no postischemic recovery of cardiac pump function (aortic flow, 0%), had decreased levels of myocardial high-energy phosphates, and were highly edematous (50% to 70% increased). After 5 hours of storage there was also poor recovery of aortic flow, coronary flow, and aortic pressure (55.0% +/- 19.4%, 67.1% +/- 5.1%, and 58.1% +/- 11.7%, respectively) but good recovery of adenosine triphosphate, creatine phosphate, and guanosine triphosphate (18.54 +/- 1.42, 29.99 +/- 2.05, and 1.64 +/- 0.14 mumol/gm dry weight, respectively). In contrast, hearts arrested and stored in STH solution for 5 hours rapidly established normal left ventricular functions (aortic flow, 111.5% +/- 2.5%; cardiac output, 99.1% +/- 1.2%; coronary flow, 85.0% +/- 3.4%; heart rate, 95.8% +/- 2.7%; and aortic pressure, 94.6%). A group of hearts arrested with STH solution but stored in saline solution recovered more slowly, had only partial return of function (aortic flow, 73.6% +/- 14.8%; p less than 0.01 vs STH/STH group), and had significantly greater tissue water content (8.020 +/- 0.080 vs 6.870 +/- 0.126 ml/gm dry wt; p less than 0.01). These results demonstrate the superior preservation of explanted hearts at 4 degrees C obtained by STH cardioplegic solution compared with UW solution under conditions used for transplantation. PMID- 1911797 TI - Gastrointestinal complications in heart and in heart-lung transplant patients. AB - Gastrointestinal complications after heart and heart-lung transplantation are being recognized and reported more frequently in the literature as a cause of significant morbidity. Between July 1983 and December 1989, 131 consecutive patients underwent 133 heart or heart-lung transplant procedures at The Johns Hopkins Hospital. Immunosuppression consisted of either cyclosporine and prednisone or cyclosporine, prednisone, and azathioprine. Twenty-eight patients (21%) had 38 gastrointestinal complications, including visceral perforations (n = 6), gastrocutaneous fistula (n = 1), retroperitoneal abscess (n = 1), cholecystitis (n = 5), gastric atony (n = 1), perianal abscess (n = 1), gastrointestinal bleeding (n = 4), esophagitis (n = 2), pancreatitis (n = 2), pancreatic abscess (n = 2), hepatitis (n = 2), cytomegalovirus infection (n = 3), and diarrhea (n = 8). Among this group of 28 patients, 17 operative procedures were needed by 13 patients (46%), for an incidence of major abdominal procedures in the entire transplant cohort of 10% (13/131). Operations included cholecystectomy (n = 5), colon resection with colostomy (n = 3), closure of perforated gastroduodenal ulcer (n = 3) and repair of gastrocutaneous fistula (n = 1), drainage of pancreatic abscess (n = 2), pyloroplasty (n = 1) and incision and drainage of perianal abscess (n = 1). The operative mortality rate was 8% (1/13). Overall survival in patients with gastrointestinal complications was no different than that in the entire transplant population. Age, gender, race, and number of rejection episodes did not correlate with the presence of gastrointestinal complications. Patients with gastrointestinal pathologic conditions necessitating surgery often had atypical presentations, with subtle clinical findings but with common general surgical problems.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1911798 TI - Value of echocardiographic determination of isovolumic relaxation time in the detection of heart transplant rejection. AB - The reproducibility of the measurement of isovolumic relaxation time in heart transplant recipients was assessed in eight heart transplant recipients. The value of routine measurement of isovolumic relaxation time and fractional shortening by echocardiography in the diagnosis of rejection was assessed by comparison with endomyocardial biopsy results in 12 patients. Despite a large, unexplained variability that will limit the application of the test in the individual patient, there was a significant fall in isovolumic relaxation time with moderate to severe rejection. PMID- 1911799 TI - Automatic internal cardioverter defibrillator: a bridge to heart transplantation. AB - The automatic internal cardioverter defibrillator (AICD) is effective in preventing death in patients with malignant ventricular arrhythmias (VT/VF) refractory to medical therapy. Because of the long waiting period for heart transplantation and the high likelihood of sudden arrhythmic death in this population, this study was undertaken to assess the value of the AICD in patients awaiting heart transplantation who have refractory VT/VF. Fourteen patients awaiting heart transplantation who had a history of VT/VF underwent AICD implantation (10 extrapericardial and four intrapericardial) via median sternotomy. All patients survived the AICD implantation and have either had heart transplantation or await transplantation at present (1 to 24 months after AICD implantation). Twelve of these patients have received a mean of 10 AICD shocks (range, 0 to 32). One patient received 19 shocks in the 24-hour period before transplantation. Two patients have died of progressive heart failure. Five patients have gone on to successful transplantation, and seven patients await heart transplantation with a functioning AICD in place. In conclusion, the AICD represents a new "bridge" to heart transplantation that is well tolerated by these high-risk patients, avoids drug side effects, and is efficacious in aborting sudden death, thereby allowing them to undergo successful heart transplantation. PMID- 1911800 TI - Reversibility of cardiac xenograft rejection in primates. AB - More than 500 people died in 1988 because of the shortage of human heart donors. Cardiac xenografts from concordant primates may help to relieve this shortage. Two groups of ABO-matched cynomolgus monkey-to-baboon heterotopic cardiac xenografts were studied. Group 1 (n = 4) control animals had no immunosuppression. Group 2 (n = 6) baboons received cyclosporine, azathioprine, and methylprednisolone acetate. Myocardial biopsy, mixed lymphocyte culture, donor-specific crossmatch, and panel-reactive antibody determinations were performed after transplantation. Biopsy-proven rejection episodes (myocyte necrosis) were treated intravenously with steroids. A follow-up biopsy was performed 7 days after the first biopsy. If rejection persisted, antithymocyte globulin (10 mg/kg/day) was given for 7 days, and another biopsy was performed. Group 1 (control) graft survival was 8, 9, 9, and 10 days (mean, 9 days). Group 2 (immunosuppressed) graft survival was 3, 16, 18, 51, 84, and 392 days (mean, 94 days). Each immunosuppressed baboons' xenograft had myocyte necrosis and variable degrees of edema, cellular infiltrates, and vascular thrombosis consistent with mixed cellular and humoral rejection within 1 week. Only one rejection episode resolved with high-dose steroid therapy alone. Two baboons' rejection episodes resolved with antithymocyte globulin treatments, but rejection recurred in both. Low levels of or delayed progression of panel-reactive antibody was associated with long-term xenograft survival. Severe steroid-resistant rejection with cell mediated and humoral immune elements developed early in our primate cardiac xenografts despite triple-drug immunosuppression. Use of antithymocyte globulin was associated with temporary resolution of rejection, but progressive increases in lymphocytotoxic antibody led invariably to eventual graft loss despite rare long-term survival. PMID- 1911801 TI - Local cyclosporine immunotherapy of heart transplants in rats enhances survival. AB - High-dose systemic cyclosporine (CyA) administration frequently results in severe side effects. To evaluate a means of limiting the adverse effects of CyA, we implanted CyA-collagen matrices (0.2 or 1 mg/kg/day released) around the cardiac homografts at the time of rat heterotopic (neck) heart transplantation. Control animals received empty collagen (nondrug) matrix implants. A fourth group received CyA matrix (1 mg/kg/day released), implanted in a distal subdermal leg pouch at the time of heart transplantation. Rejection was determined by the absence of contraction in the transplanted heart. No animal received any other immunosuppression. Parallel groups of animals had whole blood, heart, and kidney CyA levels measured on the sixth posttransplant day. Local immunosuppression with high-dose CyA in a controlled-release matrix resulted in a significant survival advantage (mean survival time, 17.1 days; control, 6.9 days; p less than 0.001). The lower dose of CyA also demonstrated significant survival benefits (10.1 days), with clinically negligible blood CyA levels and very low kidney CyA levels. Both doses of epicardial local release CyA were well absorbed locally, resulting in very high CyA levels in cardiac tissue. Local immunotherapy of transplanted hearts with CyA was shown to be an effective means of preventing rejection. If this technology can be developed, this approach may prove advantageous clinically, both in extending transplantation and in minimizing systemic side effects of immunosuppression. PMID- 1911802 TI - New assist method for orthotopic heart transplantation in the dog. AB - We used cross circulation as an assist method for orthotopic heart transplantation in eight dogs. Seven of the eight dogs could be extubated on the first to third postoperative day and were able to eat and walk several hours after extubation. The survival times and the causes of death in these eight dogs were as follows: 436 days (alive), 5 days (sudden death), 17 days (rejection), 17 days (pyothorax), 3 days (accidental death), 59 days (rejection), 19 days (pneumothorax), and 188 days (alive). None of the dogs died of any problems related to the use of cross circulation. Hematologic and biochemical studies revealed that the CK, CK-MB, LDH, GOT, GPT, and lactate levels increased shortly after the operation and returned to the preoperative values within 14 days. The blood urea nitrogen, creatinine, amylase, hematocrit, and total protein levels remained almost unchanged. No free hemoglobin was detected. These findings indicated that no severe damage occurred to the recipient's organs. The key factors for performing successful cross circulation are as follows: (1) The body weight of the support dog should be at least three times that of the recipient. (2) The systolic pressure of the support dog and the pressure gradient between the support and the recipient should be kept above 150 mm Hg and 50 mm Hg, respectively. (3) The flow rate in the arterial tube should be maintained at between 30% and 50% of the basal cardiac output of the recipient. In conclusion, cross circulation is a suitable assist method for orthotopic heart transplantation in the dog. PMID- 1911803 TI - Revised technique of heterotopic heart transplantation in rabbits. AB - The technique of heterotopically transplanting a rabbit heart into the abdominal position of a recipient rabbit is discussed. Myocardial preservation, vascular anatomy of the recipient, and general anesthetic considerations are described, as are techniques to avoid anesthetic death, hemorrhage, and paraplegia. Application of these techniques to experimental models of accelerated coronary atherosclerosis and reperfusion injury are suggested. PMID- 1911804 TI - Ischemic injury before heart transplantation does not cause coronary arteriopathy in experimental isografts. AB - In this study we investigated whether the duration of ischemia before heart transplantation was related to coronary arteriopathy. Heterotopic cardiac isografts were done in 24 Lewis rats. Group 1 hearts (n = 4) were transplanted immediately after harvesting. Hearts in groups 2 (n = 8), 3 (n = 6), and 4 (n = 6) were implanted after preservation at 4 degrees C for 1, 2, or 3 hours, respectively. No immunosuppressive drugs were given. After 120 days, grafts were removed and evaluated by means of light microscopy for coronary artery intimal proliferation. Minimal intimal thickening was noted throughout, and no differences among the groups were found. Pretransplant ischemia in the absence of other factors does not cause coronary arteriopathy after heart transplantation. PMID- 1911805 TI - Increased platelet aggregation after heart transplantation: influence of aspirin. AB - Accelerated graft coronary artery disease remains the most dramatic complication in long-term survivors of heart transplantation. The main purpose of this study was to evaluate ex vivo platelet function of heart transplant recipients as compared with that of healthy subjects and nontransplant coronary patients. The influence of aspirin, the chief antiplatelet agent, was also evaluated. The heart transplant recipients exhibited a marked platelet hyperaggregation to adenosine diphosphate as compared with the two control groups. In addition, platelets of the heart transplant recipients appeared to be resistant to the inhibitory effect of aspirin. These results could, at least partly, explain the failure of antiplatelet agents to prevent myocardial infarction in these patients. PMID- 1911806 TI - Aortic valve replacement thirty-one months after orthotopic heart transplantation. AB - Aortic valve replacement with a St. Jude prosthesis was performed 31 months after orthotopic heart transplantation in a 28-year-old male patient with Steinert's disease and idiopathic cardiomyopathy. The donor heart was reported as being normal by the cardiologist of the referring hospital. During implantation, a bicuspid aortic valve was noted, and early after the operation mild aortic regurgitation became apparent. Aortic incompetence advanced to a severe degree within 2 years after transplantation. Valve replacement, instead of retransplantation, was undertaken after careful consideration of the advantages and disadvantages of the therapeutic choice. This case report demonstrates the feasibility of valve replacement after heart transplantation and emphasizes the need for careful evaluation of potential donor hearts before harvesting. PMID- 1911807 TI - Toxoplasmosis and heart transplantation. AB - Our experience of toxoplasmosis in a series of 33 heart transplant cases was reviewed. One fatal infection was observed in a "mismatched" seronegative recipient of a heart from a seropositive donor. Two similar mismatched cases were given pyrimethamine prophylaxis and remained well. One organ recipient was found to have primary toxoplasmosis during the immediate preoperative assessment. The patient was treated with conventional therapy and remained asymptomatic in the postoperative period. Secondary reactivation of chronic infection and diagnostic confusion caused by passively acquired antibody associated with blood transfusion were not recorded. False reactions were noted in dye and latex agglutination test results. PMID- 1911808 TI - HIV infection after heart transplantation: a case report. AB - A 38-year-old man received a heart transplant because of dilated cardiomyopathy in 1984, at a time when no HIV screening test was available. Two and a half years after heart transplantation he was found to be HIV seropositive, but as of March 1990 he was still without symptoms of clinical AIDS. Neither the patient nor the organ donor belonged to any of the known risk groups, and a retrospective analysis revealed that presumably cryoprecipitates of clotting factors were the vectors of transmission. PMID- 1911809 TI - Recycled heart valves from transplant patients. AB - Forty heart transplantations were performed at the Toronto Western Hospital, University of Toronto, from October 1987 to December 1989. Each heart extracted from a recipient was examined with the view of using the aortic valve as a homograft for another patient requiring aortic valve replacement. Of the 40 explanted hearts, 26 had normal aortic valves that were potentially suitable for homografting, and 14 had aortic valves judged as unsuitable. Of the potentially suitable valves, four were preserved for ex vivo arrhythmia studies requiring aortic root perfusion and four were damaged during harvesting. The remaining 18 usable valves were sized at the time of explantation and stored in an antibiotic solution at 4 degrees C. Thirteen valves were transplanted within 10 days of harvesting, and five were discarded because no suitable recipients were available within this period. There were no operative deaths or valve-related complications in the 13 homograft valve recipients. Mean follow-up was 13 months (range, 3 to 27 months). One patient required replacement of the homograft with a mechanical prosthesis because of insufficiency and stenosis. All patients are alive, are New York Heart Association functional class status I, and have insignificant valve gradients based on Doppler echocardiography. Although hearts removed from transplant recipients are severely diseased, the aortic valves are frequently normal and should be considered for use as homografts for other patients requiring aortic valve replacement. PMID- 1911810 TI - Risk of endocarditis in donor hearts. PMID- 1911811 TI - Submucous clefts of the palate: how likely are they to be symptomatic? AB - A group of 130 patients with submucous clefts were identified from the records of the University of Pittsburgh Cleft Palate-Craniofacial Center. Many of these patients, 44 percent, remained asymptomatic into adulthood, and none required surgical intervention. A submucous cleft should be repaired in infancy only when feeding problems or unremitting ear disease is observed. The cleft should not be repaired on the theoretical basis of the potential effect of the cleft on the development of communication skills. The development of predictors that will enable professionals' valid management decisions must be developed. PMID- 1911812 TI - Symbolic representation of cleft lip and palate. AB - Since the introduction of symbolic representations of cleft lip and palate anomalies in 1964, they have served the clinician as a quick and easy method of recording these disorders. This paper reviews the evolution of the schematic classification systems and evaluates them. It then presents a new scheme that synthesizes what the authors feel are the most advanced of the existing symbolic representations. This proposed new symbolic representation scheme also specifically provides for ratings of severity (including the documentation of microforms) and facilitates computerized data storage and analysis. PMID- 1911813 TI - Increased nasal resistance induced by the pressure-flow technique and its effect on pressure and airflow during speech. AB - Although the validity of the pressure-flow technique has been verified in a number of laboratories, some questions still remain. The purpose of this study was to determine whether the procedures involved in estimating orifice size affect the pressure and airflow variables being measured. Twenty subjects with demonstrated velopharyngeal inadequacy on pressure-flow testing (VPO greater than or equal to 0.10 cm2) were assessed under two contrasting conditions. Subjects were asked to produce (p) in the word "hamper" with a) one nostril occluded by a cork as in pressure-flow testing and b) both nostrils patent. The results indicate that the increased nasal resistance resulting from occlusion of one nostril does not appreciably affect pressure and airflow associated with plosive consonant production in patients with velopharyngeal inadequacy. PMID- 1911814 TI - Motor control of velopharyngeal structures during vowel production. AB - This investigation was designed to measure the ability of normal adult speakers to exert voluntary control over velopharyngeal positioning. Speakers were asked to phonate the vowels [a] and [i] at 50 percent and 75 percent of complete velopharyngeal closure, using visual feedback of velopharyngeal opening and closing gestures from a phototransducer. The musculature of the velopharyngeal mechanism was hypothesized to act as a coordinated system that may demonstrate both motor flexibility and plasticity (Folkins, 1985) when forced to function in a novel way. Evidence of both motor system responses to a novel speaking condition was observed. Speakers were able either to phonate at intermediate closure levels without having to learn new motor rules, or to learn new rules for velopharyngeal muscle activation that resulted in the ability over time to position the velopharyngeal mechanism appropriately. As such, support is derived for the notion (Folkins, 1985) that speakers develop motor rules or coordinative structures involving the velopharyngeal mechanism that govern velopharyngeal movement. The characteristics of this coordinative structure framework has not yet been described, however, and are the subject of ongoing research efforts. PMID- 1911815 TI - Effects of different surgical regimes on nasal asymmetry and facial attractiveness in patients with clefts of the lip and palate. AB - Surgery has often been blamed for the subsequent poor growth and deformity of the nasal complex in patients with cleft lip and palate. This study compares two groups of patients with unilateral clefts of the lip and palate for the effect that different surgical techniques have on nasal symmetry and facial attractiveness. PMID- 1911816 TI - Questionnaire survey of attitudes and concerns of patients with cleft lip and palate and their parents. AB - The self-perceived problems and concerns of patients with complete unilateral cleft lip and palate and their parents were investigated. Thirty-two patients ranging in age from 16 to 25 years (mean = 19.9 years) and their parents were sent questionnaires by mail. Twenty-eight patients and 30 parents completed the questionnaires. The results suggest that the patients were satisfied with the treatment they had received. They believed that the efforts of the members of the cleft palate team had been successful, and they were generally satisfied with their overall facial appearance and speech. There were, however, specific aspects with which they were less satisfied; their nose, lip, profile, speech, and teeth. They did not feel significantly socially or emotionally handicapped, although they noted that they had been teased and that they found relations with the opposite sex difficult. Their parents were also generally satisfied with all aspects of treatment and their child's appearance and speech. They identified those areas that their child was most concerned with, but did not fully appreciate how satisfied their child was with his or her facial features. The parents felt that their children were socially and emotionally affected by their cleft and felt their school results had also been affected. PMID- 1911817 TI - Team acceptance of specific recommendations for the treatment of VPI as provided by speech pathologists. AB - This retrospective study describes the frequency of one team's acceptance of speech pathologists' recommendations for specific secondary treatment procedures for the correction of VPI for 100 consecutive patients. In addition, assessment was made of the level of success in eliminating VPI relative to treatments utilized that were recommended by speech pathologists versus level of success when treatment other than that recommended by speech pathologists were used. For the 78 patients who received the treatment procedure recommended by speech pathologists, only 10 percent continued to demonstrate any clinically significant residual speech problem associated with VPI. However, for the 22 patients who received treatment other than that which had been recommended, 32 percent continued to demonstrate clinically significant speech problems associated with VPI. Data is presented on the success rate for correcting VPI relative to specific treatment recommendations including pharyngeal flap, palatal pushback, pharyngeal wall implant, tonsillectomy, prosthetic palatal lifts, and speech therapy. PMID- 1911818 TI - Operations for microforms of cleft lip. AB - Microform cleft lip is a mild expression of cleft lip and may be difficult to repair. Its severity may be defined by the degree of downward depression of the nostril rim, skin striae of the upper lip, notching of Cupid's bow, and deformity of the vermilion border. Variation in surgical repair is reported for each type of microform cleft lip. PMID- 1911819 TI - Use of the Branemark implant in the cleft palate patient. AB - This paper describes the clinical and surgical management of a patient presenting with a unilateral alveolar cleft and associated oronasal fistula. After orthodontic expansion of the maxilla, a secondary osseous graft was placed. A single Branemark implant was subsequently utilized to allow for prosthetic restoration of the dental arch. Through case presentation, a detailed course of treatment is outlined that effectively restores the anatomy, integrity, and function of both the alveolar and dental arches. PMID- 1911820 TI - Closure of the soft palate for persistent otorrhea after placement of pressure equalization tubes in cleft palate infants. AB - Four case reports of infants with cleft palate and intractable otorrhea following the placement of pressure equalization tubes are presented. In one patient, liquids taken orally were noted to reflux through her ears. Otorrhea was refractory to medical management in all cases and was controlled only after closure of the soft palate. Persistent otorrhea may be an indication for early closure of the soft palate in these infants. PMID- 1911821 TI - Response to further comments on the pressure flow method by Selley et al. (1991) PMID- 1911822 TI - Update on the London Dysmorphology Database. PMID- 1911823 TI - The behavior of a fast-responding barbituric acid potential-sensitive molecular probe in bovine heart submitochondrial particles. AB - The barbituric acid probe diBa-C2-(5) responds to the formation of a membrane potential (delta psi) in bovine heart submitochondrial particles (SMP) by a CCCP reversible, 5-7 nm red shift of the probe absorption spectrum. This shift can be enhanced by the addition of nigericin, an observation that indicates that the probe is specifically sensitive to delta psi. Probe-SMP binding analyses indicate that, relative to the resting state, the ratio of the dye dissociation constant to the maximum number of binding sites decreases by a factor of 30 when delta psi is generated. This observation suggests that the origin of the potential dependent shift of the probe absorption spectrum is increased occupancy of the SMP membrane by diBa-C2-(5). The time course of the ATP-induced diBa-C2-(5) spectral shift in SMP was complete in nominally 0.2 s and could be described by a single-exponential rate equation. There was no evidence for a slower-phase signal when the data collection time period was increased to 250 s. The apparent first order rate constants obtained from the single exponential analyses of the barbituric acid ATP-generated signal, however, were a linear function of probe concentration at fixed SMP membrane concentration. The resulting second-order rate constant obtained by linear regression was nominally 1 x 10(7) M (dye)-1 s 1; this value is two to three orders of magnitude higher than that of a number of other well-established probes of delta psi in mitochondrial preparations. Based on the invariance of the kinetics of the oxidation of cytochromes c and c1 by ATP driven reversed electron transport in the presence and absence of the probe, diBa C2-(5) does not appear to permeate the SMP membrane on a time scale of milliseconds to several minutes. PMID- 1911824 TI - A novel mechanism of cation/substrate cotransport: Na+/H+/adenosine cotransport in Vibrio parahaemolyticus. AB - Adenosine is actively transported with Na+ in Vibrio parahaemolyticus (Sakai, Y., Tsuda, M., Tsuchiya, T. (1987) Biochim, Biophys. Acta 893, 43-48). The proton conductor carbonylcyanide m-chlorophenylhydrazone, CCCP, strongly inhibited active transport of adenosine at pH 8.5 as well as at pH 7.0. This seemed peculiar because the driving force, an electrochemical potential of Na+, is established by the Na(+)-extruding respiratory chain at pH 8.5 in this organism, although it is established by the function of the Na+/H+ antiporter at pH 7.0. This suggested that H+ might be involved in the adenosine transport. We detected H+ uptake induced by adenosine influx in V. parahaemolyticus cells in the presence of Na+, but not in its absence, suggesting the occurrence of Na+/H+/adenosine cotransport. We isolated formycin A-resistant mutants which showed defective adenosine transport. The mutation resulted in simultaneous losses of Na+ uptake and H+ uptake induced by adenosine. In revertants from these mutants the Na+ uptake and H+ uptake were restored simultaneously. The frequencies of reversion were in the order of 10(-7), indicating that the mutations were single mutations; namely that Na+/adenosine cotransport and H+/adenosine cotransport took place via the same carrier. Thus, we conclude that adenosine is transported by the novel mechanism of Na+/H+/adenosine cotransport in V. parahaemolyticus. PMID- 1911825 TI - Direct evidence of the metal-free nature of sirohydrochlorin in desulfoviridin. AB - We have obtained direct evidence that the majority of the sirohydrochlorin chromophore in the dissimilatory sulfite reductase desulfoviridin from Desulfovibrio gigas, is not associated with any metal. The evidence comes from resonance Raman measurements of native and deuterated samples of desulfoviridin. The breathing mode v4 (or v4*) at 1336 cm-1 in the native enzyme is downshifted to 1326 cm-1 upon deuteration. This mode is not sensitive to deuteration if a metal is present at the center of the chromophore inside protein or in solution. The results also establish the existence of exchangeable core hydrogen(s) at the pyrrolic nitrogen(s). PMID- 1911826 TI - Pharmacokinetics of stealth versus conventional liposomes: effect of dose. AB - Liposomes which substantially avoid uptake into the mononuclear phagocyte system (MPS), termed Stealth liposomes, have recently been formulated (Allen, T.M. and Chonn, A., (1987) FEBS Lett. 223, 42-46). The pharmacokinetics of stealth liposomes as a function of liposome dose and a comparison to conventional liposome pharmacokinetics, was the subject of the present study. We have examined the tissue distribution of two different formulations of stealth liposomes, i.e., sphingomyelin:egg phosphatidylcholine:cholesterol:monosialoganglioside GM1 (SM:PC:CHOL:GM1) 1:1:1:0.2 and SM:PC:CHOL:polyethylene glycol distearoylphosphatidylethanolamine (PEG(1990)-DSPE) 1:1:1:0.2, and compared them with the tissue distributions seen for a liposomal formulation which is avidly removed from circulation by the cells of the MP system (PC:CHOL, 2:1). Tissue distribution in mice was examined over a 100-fold concentration range (0.1 to 10 mumol phospholipid/mouse) and at several time points over a 48 h time period. Liposome size ranged from 92-123 nm in diameter for all compositions. Clearance from blood of PC:CHOL liposomes following intravenous administration showed a marked dose dependence (i.e., saturation-type or Michaelis-Menten kinetics), with MPS uptake decreasing and % of injected dose in blood increasing as dose increased, over the entire dosage range. Injection of stealth liposomes, on the other hand, resulted in % of injected doses of liposomes in MPS, blood and carcass which were dose-independent and log-linear (first order kinetics) over the entire dosage range. The doses of stealth liposomes containing PEG(1900)-DSPE required for MPS saturation was higher than 10 mumol phospholipid/mouse or 400 mumol/kg. The dosage-independence of the pharmacokinetics of stealth liposomes and their lack of MPS saturation within the therapeutic dose range are two more assets, in addition to the prolonged circulation half-lives, leading towards their eventual use as drug delivery systems in the clinic. PMID- 1911827 TI - Kidney brush-border membrane transporters: differential sensitivity to diethyl pyrocarbonate. AB - The effects of the histidine modifier, diethyl pyrocarbonate (DEPC), on brush border membrane transport systems were studied in rat kidney. DEPC caused a strong inhibition of sodium-dependent phosphate and D-glucose uptake. Phosphate uptake remained linear up to 10 s in control and DEPC-treated membrane vesicles. The D-glucose carrier was more sensitive than the phosphate carrier with half times of inhibition being 4 and 7 min, respectively. Sodium-independent phosphate and D-glucose uptake remained unaffected by DEPC. Intravesicular volume and two enzyme activities endogenous to the luminal membrane (alkaline phosphatase and aminopeptidase M) remained unaffected by DEPC. Increasing the preincubation pH from 5 to 9 increased phosphate transport inhibition caused by DEPC from 73 to 88% in the presence of DEPC. Hydroxylamine was able to completely reverse phosphate uptake inhibition by DEPC (100%), but only partially reversed the D glucose uptake inhibition (16%). Sodium or substrate (D-glucose or phosphate) in the preincubation media were unable to protect their respective carriers from DEPC. Sodium-dependent transport of L-glutamine, L-phenylalanine, L-leucine, L alanine, L-glycine, beta-alanine and L-proline were inhibited at different levels ranging from 70 to 90%. Three transport processes were found insensitive to DEPC modification: L-glutamate, L-lysine and D-fructose. None of the amino acid transporters was protected against DEPC by sodium and/or their respective substrates. Sodium influx was inhibited by DEPC (47%) in the absence of any substrate. Our results show a differential sensitivity of sodium-dependent transporters to DEPC and suggest an important role for histidine residues in the molecular mechanisms of these transporters. More experiments are in progress to further characterize the residue(s) involved in these transport inhibitions by DEPC. PMID- 1911829 TI - Epifluorescence microscopic observation of monolayers of dipalmitoylphosphatidylcholine: dependence of domain size on compression rates. AB - A fluorescence microscopic technique was used to observe phase transitions in monolayers of DPPC. The sizes of the domain structures observed were found to be dependent on the rate of compression of the monolayer. The distribution of domain sizes for different rates of compression were unimodal, but the scatter in the sizes was greater during slow compressions. PMID- 1911828 TI - Spectra of voltage-sensitive fluorescence of styryl-dye in neuron membrane. AB - The voltage sensitivity of fluorescence of an aminobenzstyryl-pyridinium dye (di4 ANEPPS) is characterized in Retzius cells dissociated from the leech. The modulation of the complete spectra of excitation and emission is determined. The spectral changes induced by depolarization are described by a blue shift of the absorption spectrum, by a weaker blue shift and an enhanced width of the fluorescence spectrum and by a decrease of the yield of fluorescence. These changes are attributed tentatively to a superposition of electrochromism and of field-induced resolvation. PMID- 1911830 TI - Deuterium NMR investigation of polymorphism in stratum corneum lipids. AB - The intercellular lipid lamellae of stratum corneum constitute the major barrier to percutaneous penetration. Deuterium magnetic resonance and freeze-fracture electron microscopic investigation of hydrated lipid mixtures consisting of ceramides, cholesterol, palmitic acid and cholesteryl sulfate and approximating the stratum corneum intercellular lipid composition, revealed thermally induced polymorphism. The transition temperature of bilayer to hexagonal transition decreased as the ratio of cholesterol to ceramides in these mixtures was lowered. Lipid mixtures in which the stratum corneum ceramides were replaced by synthetic dipalmitoylphosphatidylcholine did not show any polymorphism throughout the temperature range used in the present study. The ability of the ceramide containing samples to form hexagonal structures establishes a plausible mechanism for the assembly of the stratum corneum intercellular lamellae during the final stages of epidermal differentiation. Also, the bilayer to hexagonal phase transition of these nonpolar lipid mixtures could be used to enhance the penetration of drugs through skin. PMID- 1911831 TI - Effective charge of melittin upon interaction with POPC vesicles. AB - The binding of bee venom melittin to small unilamellar vesicles and large nonsonicated multilamellar bilayer membranes composed of 1-palmitoyl-2-oleoyl-sn glycero-3-phosphocholine (POPC) was studied by means of circular dichroism, 31P NMR and electrophoretic mobility. The melittin binding isotherm for small unilamellar vesicles (SUV) could be described by a partition equilibrium with Kp = (6 +/- 1).10(4) M-1. Electrostatic effects were taken into account by means of the Gouy-Chapman theory. Combining the partition equilibrium with the Gouy Chapman analysis suggested an effective charge for melittin of Zp = 1.9, which is lower than the true electric charge of 5-6. The variation of the 31P-NMR signal of SUV showed the change in potential at the phosphodiester moiety of the lipid upon addition of melittin. This potential change was lower than that for an ion with an electrical charge of 5-6 and corresponded to a charge of 1.5. Electrophoretic mobility measurements with multilamellar vesicles confirmed the charge reduction effect. These experimental results show that the use of the simple Gouy-Chapman theory requires an effective electrical charge of the melittin which is lower than the formal charge. PMID- 1911832 TI - An energy-dependent efflux system for potassium ions in yeast. AB - An efflux of potassium ions was demonstrated in mutants of yeast cells lacking a functional high affinity carrier system for monovalent cations. This efflux showed the following characteristics: (a) It was stimulated by the presence of a substrate, either glucose or ethanol. (b) It was stimulated by several cationic organic molecules, such as ethidium bromide, dihydrostreptomycin, diethylaminoethyldextran, and also by trivalent cations, such as Al3+ and lanthanides; this stimulation also depended on the presence of a substrate. (c) K+ efflux was decreased in yeast mutants with decreased ATPase activity, which generated a lower membrane potential. (d) Although the efflux appeared to be of an electrogenic nature, producing hyperpolarization of cells, it was accompanied by the efflux of phosphate, probably as an anion partially compensating for the large amount of cations leaving the cell. (e) K+ efflux was also accompanied by an uptake of protons. (f) The efflux appeared more clearly in cells grown in YPD medium, and not in more complex media nor in the same YPD medium if supplemented with Ca2+ or Mg2+. Efflux of monovalent cations produced by Tb3+ and organic cationic agents was also demonstrated in wild type strains. This efflux system appears to be, at least partially, electrogenic, but seems to be also an exchange system for protons and to function as a symport with phosphate; it may be involved in the regulation of the internal pH of the cell, and appears to be regulated by its link to the energetic status of the cell, probably through the membrane potential. PMID- 1911833 TI - Electromechanical stability of planar lipid membranes from bipolar lipids of the thermoacidophilic archebacterium Sulfolobus acidocaldarius. AB - Stable planar membranes have been obtained from the bipolar lipid glycerol dialkyl nonitol tetraether (GDNT) extracted from the thermoacidophilic archebacterium Sulfolobus acidocaldarius. The electric capacity Cm, the resistance Rm and tension sigma of these membranes were measured. The dependence of the bipolar lipid membranes mean life time tau 1 on voltage was investigated. It was shown that the irreversible electric breakdown of membranes from GDNT and usual phospholipids is due to the same mechanism, viz., due to formation of a hydrophilic pore with an overcritical radius. Under electric field the GDNT molecules take U-shape, and the polar headgroups of such molecules cover the pore's interior. PMID- 1911834 TI - Phospholipase C activity-induced fusion of pure lipid model membranes. A freeze fracture study. AB - The structural effects of in situ production of diacylglycerol by phospholipase C in pure lipid model membranes have been examined by freeze fracture electron microscopy. Phospholipase C-activity induces massive aggregation and fusion of large unilamellar lipid vesicles and leads to the formation of a 'sealed' lipid aggregate; the outer membrane of this aggregate appears to be continuous. In some areas lipid arranges into a honeycomb structure; this structure is probably a precursor of a discontinuous inverted (type II) cubic phase. Similarly, enzyme treatment of multilamellar vesicles leads to extensive membrane fusion and vesiculation. Thus morphological evidence is obtained showing the ability of phospholipase C to induce bilayer destabilization and fusion. It is speculated that phospholipase C-induced membrane fusion involves a type II fusion intermediate induced by diacylglycerol produced locally. PMID- 1911835 TI - Spectroscopic evidence for NADH-induced conformational changes in rabbit muscle aldolase. AB - The intrinsic fluorescence (steady-state spectra, anisotropy and nanosecond decay) in combination with phosphorescence at room temperature were used to detect and characterize conformational changes in rabbit muscle aldolase accompanying the NADH-binding process. Ligand binding has entailed a decrease in aldolase fluorescence intensity, a blue shift in its maximum and a polarization increase in a long wavelength part of the emission spectrum. The NADH binding induces the changes in room temperature phosphorescence - higher intensity and longer lifetime. The excited state energy transfer from tryptophans to NADH is not observed, and the character of spectroscopic changes on NADH binding allows us to reveal the spectroscopic heterogeneity among the tryptophan residues. The character, location of protein conformational changes associated with the binding of NADH and their relation to the tryptophans' microenvironment in aldolase are discussed. PMID- 1911836 TI - Free calcium and calpain I activity. AB - Activation of purified calpain I proceeds through a Ca(2+)-induced autolysis from the 80 kDa catalytic subunit to a 76 kDa form via an intermediate 78 kDa form, and from a 30 kDa form to a 18 kDa form as the result of two autocatalytic processes (intra and intermolecular). The minimum Ca2+ requirements for autolysis and proteolysis have been determined by physico-chemical and electrophoretic methods in the presence or absence of a digestible substrate. According to our results the activation process needs less free Ca2+ than the proteolysis of a digestible substrate, which means that proteolysis is really subsequent to activation. For very low Ca2+ levels, a digestible substrate does not initiate the calpain I activation process. In the presence of phospholipid vesicles, such as PI, PS or a mixture of PI (20%), PS (20%) and PC (60%), the apparent kinetic constants of activation are greatly increased without any change in the initial velocity of the substrate proteolysis. Thus, enzyme activation and substrate proteolysis are observed as independent phenomena. These results obtained from experiments using low free Ca2+ concentrations enable us to propose a hypothesis for the mechanism of regulation by which the enzyme could be activated in the living cell. PMID- 1911837 TI - The binding of nitrate to the human anion exchange protein (AE1) studied with 14N nuclear magnetic resonance. AB - The binding of [14N]nitrate to the human erythrocyte anion transport protein, AE1, was studied using 14N nuclear magnetic resonance spectroscopy (14N-NMR). The line-width at half-height of the 14NO3- resonance increased in direct proportion to the concentration of erythrocyte ghost protein. Addition of the AE1 specific inhibitor 4,4'-dinitrostilbene-2,2'-disulfonate markedly reduced this line broadening, indicating that the broadening was predominantly due to a specific interaction between nitrate and AE1. The dependence of the AE1 specific line broadening on nitrate concentration had a first-order dissociation constant KD of 6.9 +/- 0.9 mM. In contrast, Cl- interaction with AE1 studied by 35Cl-NMR showed a chloride concentration-dependent line-broadening with a KD of 74 +/- 10 mM, indicating that AE1 has a higher affinity for nitrate than for chloride. Bicarbonate and chloride were found to be competitive inhibitors of the AE1 specific 14NO3- line-broadening (94 +/- 6% and 101 +/- 3% inhibition, respectively). Based on the concentration dependence of inhibition and using a model of competitive inhibition, the KD of bicarbonate binding to AE1 was estimated to be 5.4 +/- 1.3 mM. Nitrate is a structural analog of bicarbonate, making the interaction of nitrate with AE1 a good model for the bicarbonate-AE1 interaction. The 14N-NMR nitrate binding assay, along with the 35Cl-NMR binding assay now in use, will provide a powerful tool for studying the structure of the AE1 binding site for both physiologic substrates, bicarbonate and chloride. PMID- 1911839 TI - Calorimetric analysis of antifreeze glycoproteins of the polar fish, Dissostichus mawsoni. AB - Solutions of antifreeze glycoproteins 1 through 5 and 8 were analyzed for activity by differential scanning calorimetry. With a scan rate of 1 degree C min 1, antifreeze glycoproteins 1-5 (20 mg/ml) revealed antifreeze activity with a delay in the freeze exotherm during cooling in the presence of ice. Antifreeze glycoprotein 8 (60 mg/ml), however, did not reveal antifreeze activity. When a 0.1 degree C min-1 scan rate was used, glycoproteins 1-5 again yielded a delay in the freeze onset, but the exotherm consisted of multiple events. At the slower scan glycoprotein 8 revealed an initial freeze followed by multiple exothermic events resembling those of glycoproteins 1-5. Thermograms exhibiting antifreeze activity had an initial shoulder in the exotherm direction upon cooling followed by a delay before the exotherm. The shoulders were correlated with c-axis ice growth observed in visual methods. The glycoprotein antifreezes had a linear increase in activity with decreased ice content. PMID- 1911838 TI - Hemoglobin polymerization in sickle cells studied by circular polarized light scattering. AB - We have studied intracellular polymerization of hemoglobin S in suspensions of small populations of sickle cells using circular polarized light scattering. We argue that the preferential scattering of right circular polarized light (as expressed by measurements of the S14 Mueller scattering matrix element) directly reflects the amount of polymer inside cells. This technique has made it possible to investigate the effect of oxygen tension, cell density and osmotic stress on intracellular hemoglobin polymerization. Using S14 to determine hemoglobin polymer, we show that the polymer increases with deoxyhemoglobin concentration, that cells containing higher hemoglobin concentrations show significantly more polymer than cells containing less hemoglobin, and that polymerization occurs in sickle-trait cells in hypertonic solutions as the oxygen tension in the suspension is reduced. We also present kinetic measurements of polymerization, including that induced by osmotic shock. Finally, we demonstrate that the total light scattered (S11 Mueller scattering matrix element) that is routinely measured simultaneously with S14 can be used to estimate the percent of reduced (deoxy) Hb in the sample. These experiments demonstrate the potential of this technique to monitor hemoglobin polymerization simultaneously with oxygen dissociation under a wide variety of physiological conditions. PMID- 1911840 TI - A calmodulin endoproteinase from mitochondrial membranes. AB - A proteinase specific for calmodulin has been identified in a crude rat kidney Triton-extracted or sonicated mitochondrial fraction and solubilized by EGTA extraction of these membranes. Mitochondrial fractions from other tissues had less activity, with relative activities: kidney = spleen greater than testes greater than liver, and no detectable activity in either brain or skeletal muscle. This enzyme is active in the presence of EGTA, but not in the presence of calcium, and cleaves calmodulin into three major peptide fragments with Mr 6000, 9000 and 10,000. N-methylated and non-methylated calmodulins were both cleaved by calmodulin proteinase and while troponin was a poor substrate, it was cleaved in the presence of either calcium or EGTA. No other EF hand calcium-binding proteins or other major mitochondrial proteins were cleaved by this enzyme. The peptides resulting from calmodulin proteinase action were isolated by reverse-phase high performance liquid chromatography (HPLC) and sequenced. Sequence analysis indicated that calmodulin proteinase cleaves calmodulin at Lys-75. The effects of proteinase inhibitors indicate that calmodulin proteinase is a trypsin-like enzyme belonging to the serine endopeptidase family of enzymes. PMID- 1911841 TI - Kinetics and mechanisms of reduction of Cu(II) and Fe(III) complexes by soybean leghemoglobin alpha. AB - The reduction of low-molecular-weight Cu(II) and Fe(III) complexes by soybean leghemoglobin alpha was characterized using both kinetic analysis and 1H-NMR experiments. Whereas Fe(III) (CN)6(3-) was reduced through an outer sphere transfer over the exposed heme edge, all other Cu(II) and Fe(III) complexes investigated were reduced via a site-specific binding of the metal to the protein. Reduction of all metal complexes was enhanced by decreasing pH while only Fe(III)NTA reduction kinetics were altered by changes in ionic strength. Rates of reduction for both Cu(II) and Fe(III) were also affected inversely by the effective binding constant of the metal chelate used. NMR data confirmed that both Cu(II)NTA and Fe(III)NTA were bound to specific sites on the protein. Cu(II) bound preferentially to distal His-61 and Fe(III) exerted its greatest effect on two surface lysine residues with epsilon proton resonances at 3.04 and 3.12 ppm. The Fe(III)NTA complex also had a mild but noticeable line broadening effect on the distal His-61 singlet resonance near 5.3 ppm. Like hemoglobin and myoglobin, leghemoglobin might function not only as an oxygen carrier, but also as a biological reductant for low-molecular-weight Cu(II) and Fe(III) complexes. PMID- 1911842 TI - Effect of cholesta-3,5-dien-7-one on human liver aldehyde dehydrogenase. AB - A recently isolated cholesterol oxidation product, cholesta-3,5-dien-7-one, which was present at high concentrations in fatty/cirrhotic alcoholic liver was identified as a potent endogenous inhibitor of the cytosolic, E1, isozyme of aldehyde dehydrogenase (EC 1.2.1.3). The oxysterol was a less potent inhibitor of mitochondrial, E2, isozyme. The inhibition of the E1 isozyme was irreversible on the IEF gels, upon dilution and with 33 microM 2-mercaptoethanol during activity assay. The calculated 1-50% values from the inhibition curves for the E1 isozyme were 5-10 microM and approx. 180 microM for the E2 isozyme. The E3 isozyme was not sensitive to the oxysterol. Judging from the Lineweaver-Burk plot, the inhibition of the E1 isozyme with a constant concentration of cholesta-3,5-dien-7 one (52 microM) appeared to be noncompetitive. PMID- 1911843 TI - Effect of linking allyl and aromatic chains to histidine 170 in horseradish peroxidase. AB - Histidine residues in horseradish peroxidase (HRP) were modified chemically with diethyl pyrocarbonate, 4,omega-dibromoacetophenone or diallylpyrocarbonate. Histidines were chosen as His-170, the fifth ligand of the heme iron atom, forms part of the active site of this enzyme. Good yields of hemoprotein were obtained in all cases. Analysis by HPLC of peptides obtained after tryptic digestion showed that His-170 of HRP was in fact modified. The specific activity remained satisfactory after chemical modification of the histidine residues, and so the active site of HRP can thus be altered without a dramatic loss of hemoprotein or peroxidase activity. This may open routes to the preparation of novel biocatalysts. PMID- 1911844 TI - Isolation and complete amino acid sequence of two fibrinolytic proteinases from the toxic Saturnid caterpillar Lonomia achelous. AB - The major toxic and fibrinolytic activity of the saliva and hemolymph of the larval form of Lonomia achelous was purified to homogeneity by a combination of metal chelate and affinity chromatography. Two apparent isozymes, Achelase I (213 amino acids, pIcalc = 10.55) and Achelase II (214 amino acids, pIcalc = 8.51), were sequenced by automated Edman degradation, and their C-termini confirmed by Fourier-transform mass spectrometry. The calculated molecular weights (22,473 and 22,727) correspond well to Mr estimates of 24,000 by SDS-PAGE. No carbohydrate was detected during sequencing. The enzymes degraded all three chains of fibrin, alpha greater than beta much greater than gamma, yielding a fragmentation pattern indistinguishable from that produced by trypsin. Chromogenic peptides S-2222 (Factor Xa and trypsin), S-2251 (plasmin), S-2302 (kallikrein) and S-2444 (urokinase) were substrates while S-2288 (broad range of serine proteinases including thrombin) was not hydrolyzed. Among a range of inhibitors Hg+2, aminophenylmercuriacetate, leupeptin, antipain and E-64 but not N-ethylmaleimide or iodoacetate abolished the activity of the purified isozymes against S-2444. Phenylmethylsulfonyl fluoride, soybean trypsin inhibitor and aprotinin were less effective. The presence of the classic catalytic triad (histidine-41, aspartate 86 and serine-189) suggests that Achelases I and II may be serine proteinases, but with a potentially free cysteine-185 which could react with thiol proteinase directed reagents. PMID- 1911845 TI - Purification of the proteinase from group B streptococci that inactivates human C5a. AB - We previously reported that group B streptococci (GBS) possess a cell-associated activity that inactivates the chemotactic activity generated in zymosan-activated serum by cleaving a specific site within the carboxy termini of C5a and C5adesarg. This inactivates the major chemoattractants for neutrophils that are generated when serum complement is activated. We now report the isolation of the enzyme responsible for the proteolytic cleavage of C5a. Treatment of GBS with mutanolysin, an endo-N-acetyl muramidase, released activity from GBS which destroyed the functional activity of C5a. The soluble activity was purified to homogeneity by hydroxyapatite, ion-exchange and gel-filtration chromatography. Analysis by SDS-PAGE showed that the enzyme (GBS C5a-ase) has an Mr of approx. 120,000. The GBS C5a-ase appears to be a serine esterase on the basis of its sensitivity to di-isopropyl fluorophosphate. This enzyme is distinct from the C5a cleaving enzyme produced by group A streptococci, since the two bacterial products migrate differently on SDS-PAGE, and lack antigenic cross reactivity. This enzyme may play a role in the pathogenesis of group B streptococcal disease through its ability to rapidly inactivate the potent neutrophil agonist, C5a, at sites of infection. PMID- 1911846 TI - The importance of precise positioning of negatively charged carboxylate in the catalytic action of human lysozyme. AB - The role of aspartic acid 53 of human lysozyme (peptidoglycan N acetylmuramoylhydrolase, EC 3.2.1.17) has been investigated by a site-directed mutagenesis. In order to clarify the importance of precise positioning of the negatively charged carboxylate group in the active site geometry, both the three dimensional structure and the enzymatic function of glutamic acid 53 human lysozyme (Glu-53 human lysozyme) have been characterized in comparison with those of wild type enzyme. Glu-53 human lysozyme was crystallized and analysed by X-ray crystallography. No remarkable difference in the conformation of whole molecule except the side chain of 53rd residue was observed. In spite of full retention of the binding activities against either beta-1,4-linked trisaccharide of N acetylglucosamine ((GlcNAc)3) or the corresponding hexasaccharide ((GlcNAc)6), the conversion of Asp-53 to Glu reduced the enzymatic activities against both bacterial cell substrate and p-nitrophenyl penta-N-acetyl-beta(1----4) chitopentaoside (p-NO2-(GlcNAc)5) to a few percent of the activities of wild type enzyme. Calculation of electrostatic potential around the reaction center predicted that no significant change in pKa of Glu-35 was caused by the mutation. These results indicate that the precise positioning of the negatively charged carboxylate in the geometry of reaction center is essential for the rate enhancement in the catalytic action of lysozyme, and suggest that Asp-53 of human lysozyme participates in the catalytic action not simply in an electrostatical manner but partly in a nucleophilical manner. PMID- 1911847 TI - Tissue inhibitor of metalloproteinases-2 inhibits the activation of 72 kDa progelatinase by fibroblast membranes. AB - We report that monolayers of human fibroblasts stimulated with concanavalin A were able to activate 72 kDa progelatinase but not 95 kDa progelatinase. The activating capacity of fibroblasts appeared approx. 6 h after concanavalin A stimulation and was blocked by cycloheximide. The activation of 72 kDa progelatinase was readily inhibited by TIMP-2 but only poorly by TIMP-1. Plasma membranes isolated from the fibroblasts were capable of activating 72 kDa progelatinase. The cleavage products of the plasma membrane-mediated activation of 72 kDa progelatinase corresponded to those of organomercurial-induced self cleavage. Only inhibitors of metalloproteinase self-cleavage inhibited the activating capacity of plasma membrane preparations, although the activating capacity was destroyed by trypsin and heat. As with the fibroblast monolayers, TIMP-2 was a potent inhibitor of the membrane-mediated activation whereas TIMP-1 was less so. PMID- 1911848 TI - Duck liver malic enzyme: sequence of a tryptic peptide containing the cysteine residue labeled by the substrate analog bromopyruvate. AB - Malic enzyme of duck liver is alkylated by bromopyruvate with half-of-the-sites stoichiometry, and with accompanying loss of oxidative decarboxylase and enhancement of pyruvate reductase activities as was previously shown for the pigeon enzyme (Hsu, R.Y. (1982) Mol. Cell. Biochem. 43, 3-26). In the present work, the alkylated enzyme is shown to bind NADPH, but not L-malate in the presence of MnCl2, indicating impairment of the enzyme site for the substrate and/or divalent metal. The enzyme was differentially labeled by 3-bromo-1-[14C] pyruvate and digested with TPCK-treated trypsin. Two peptides bearing the susceptible residue were purified by high-performance liquid chromatography and sequenced. Peptide II has the sequence of FMPIVYTPTVGLAXQQYGLAFR, corresponding to residues 86-107 (temporary numbering) of the duck enzyme; cysteine-99(x) is not detected, indicating that it is the target of modification by bromopyruvate. Peptide I is a truncated form of peptide II lacking five amino acid residues at the C-terminal. Cysteine-99 is conserved in malic enzymes from duck, rat, mouse, maize, human, Flaveria trinervia and Bacillus stearothermophilus. PMID- 1911849 TI - A fluorometric study with 1-anilinonaphthalene-8-sulfonic acid (ANS) of the interactions of ATP and ADP with rubisco activase. AB - The interactions of ATP and ADP with rubisco activase purified from spinach were investigated by measuring enhanced fluorescence due to ANS-binding to the protein. Evidence of conformational changes was observed from the differences in the interaction of ANS with rubisco activase in the presence of excess ATP and ADP. Fluorescent changes associated with the titration of a rubisco activase-ANS mixture with ATP and ADP indicated that the binding of ADP to rubisco activase was much tighter than that of ATP. The concentration of Mg2+ and pH had significant effects on the affinities of rubisco activase for ATP and ADP, with higher pH and Mg2+ concentration facilitating the binding of ATP to rubisco activase in the presence of ADP. The physiological implications of the binding characteristics of ATP and ADP with rubisco activase on the light-dark regulation of rubisco are discussed. PMID- 1911850 TI - Polymerization and solubility of Ni(II)-Fe(II) hybrid Hb S. AB - Polymerization of half-liganded Hb S was investigated using Ni(II)-Fe(II) hybrid Hb S, in which heme in either alpha or beta s subunits is replaced by Ni (II) protoporphyrin IX. Studies on the polymerization of these hybrid hemoglobins were carried out under aerobic conditions. Both alpha 2 (Ni) beta 2s (Fe-CO) and alpha 2 (Fe-CO) beta 2s (Ni) polymerized with a distinct delay time as do native deoxy Hb S and Ni(II) Hb S. However, the critical concentration for polymerization of half-liganded Hb S, alpha 2 (Ni) beta 2s (Fe-CO) and alpha 2 (Fe-CO) beta 2s (Ni), was 4- and 8-times higher, respectively, than that of Ni(II)-Hb S. Kinetics of polymerization of both deoxygenated hybrid hemoglobins with CO completely removed were the same, although the critical concentrations for polymerization were intermediate between those for deoxy-Hb S and Ni(II)-Hb S. These results suggest that the small tertiary conformational change associated with the doubly liganded state may be much less favorable to polymerization than the completely unliganded state of Hb S. The conformational change depends on whether alpha or beta chain is liganded. The ease of polymerization and low solubility of sickle hemoglobin is dependent not only on quaternary, but on tertiary structural changes, as well as on the substitution of Val for Glu at the beta 6 position. PMID- 1911851 TI - A principal neutralizing domain of human immunodeficiency virus type 1 interacts with proteinase-like molecule(s) at the surface of Molt-4 clone 8 cells. AB - A principal neutralizing domain (PND) of the major envelope glycoprotein (gp120) of the HTLV-III BH10 strain of human immunodeficiency virus type 1 (HIV-1) has significant amino acid similarities to a reactive site of Kunitz-type basic proteinase inhibitors. We therefore thought that the PND may interact with cellular proteinase-like molecule(s) upon HIV-1 infection and measured the cellular proteolytic activities at the surface of intact Molt-4 clone 8 cells, which are highly susceptible to HIV-1 infection. The cells preferentially cleaved succinyl-Leu-Leu-Val-Tyr-4-methylcoumaryl-7-amide, a good substrate of chymotrypsin, and the activity was strongly inhibited by N-tosyl-L-phenylalanyl chloromethyl ketone (IC50 = 11.5 microM) and chymostatin (IC50 = 4.8 microM). A synthetic peptide of 24 residues (amino acids 308-331) that correspond to the PND also inhibited the cellular proteolytic activity in a dose-dependent manner (IC50 = 79.2 microM). The inhibition was still observed at low temperature (IC50 = 42.7 microM) and even after the peptide-treated cells were washed. We therefore think that the peptide interacts with proteinase-like molecule(s) located at the surface of the cells. The synthetic peptides from four other strains of HIV-1 corresponding to the PND similarly inhibited the proteolytic activity. These results may be helpful to clarify the novel mechanism(s) for HIV-1 infection. PMID- 1911852 TI - Purification and characterization of glutathione S-transferases from rat pancreas. AB - Glutathione S-transferases (GSTs) of rat pancreas have been characterized and their interrelationship with fatty acid ethyl ester synthase (FAEES) has been studied. Seven GST isozymes with pI values of 9.2, 8.15, 7.8, 7.0, 6.3, 5.9 and 5.4 have been isolated and designated as rat pancreas GST suffixed by their pI values. Structural, immunological and kinetic properties of these isozymes indicated that GST 9.2 belonged to the alpha class, GST 7.8, 7.0, 6.3 and 5.9 belonged to the mu class, whereas GST 8.15 and 5.4 belong to pi class. The N terminal sequences and pI values of the mu class isozymes suggested that rat GST subunits 3, 4 and 6 may be expressed in pancreas. N-Terminal sequences of both the pi class isozymes, GST 8.15 and 5.4, were similar to that of GST-P, but there were significant differences in the substrate specificities of these two enzymes. Results of peptide finger print studies also indicated minor structural differences between these two isozymes. None of the GST isozymes of rat pancreas expressed FAEES activity. Rat pancreas had a significant amount of FAEES activity, but it segregated independently during the purification of GST indicating that these two activities are expressed by different proteins and are not related as suggested previously. PMID- 1911853 TI - Purification and properties of 5,10-methylenetetrahydromethanopterin dehydrogenase and 5,10-methylenetetrahydromethanopterin reductase, two coenzyme F420-dependent enzymes, from Methanosarcina barkeri. AB - 5,10-Methylenetetrahydromethanopterin dehydrogenase and 5,10 methylenetetrahydromethanopterin reductase have been purified to homogeneity by a factor of 86 and 68, respectively, from methanol-grown Methanosarcina barkeri cells. The dehydrogenase was isolated as a hexamer of a single 35 kDa subunit, whereas the reductase was composed of four identical 38 kDa subunits. The purified oxygen-stable enzymes catalyzed the oxidation of 5,10 methylenetetrahydromethanopterin and methyltetrahydromethanopterin with Vmax values of 3000 and 200 mumol min-1 mg-1, respectively. The methanogenic electron carrier coenzyme F420 was a specific electron acceptor for both enzymes. Steady state kinetics for the two enzymes were in agreement with ternary complex (sequential) mechanisms. Methylene reductase and methylene dehydrogenase are proposed to function in the methanol oxidation step to CO2. PMID- 1911854 TI - Determination of disulfide array and subunit structure of taste-modifying protein, miraculin. AB - The taste-modifying protein, miraculin (Theerasilp, S. et al. (1989) J. Biol. Chem. 264, 6655-6659) has seven cysteine residues in a molecule composed of 191 amino acid residues. The formation of three intrachain disulfide bridges at Cys 47-Cys-92, Cys-148-Cys-159 and Cys-152-Cys-155 and one interchain disulfide bridge at Cys-138 was determined by amino acid sequencing and composition analysis of cystine-containing peptides isolated by HPLC. The presence of an interchain disulfide bridge was also supported by the fact that the cystine peptide containing Cys-138 showed a negative color test for the free sulfhydryl group and a positive test after reduction with dithiothreitol. The molecular mass of non-reduced miraculin (43 kDa) in sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) was nearly twice the calculated molecular mass based on the amino acid sequence and the carbohydrate content of reduced miraculin (25 kDa). The molecular mass of native miraculin determined by low-angle laser light scattering was 90 kDa. Application of a crude extract of miraculin to a Sephadex G-75 column indicated that the taste-modifying activity appears at 52 kDa. It was concluded that native miraculin in pure form is a tetramer of the 25 kDa-peptide and native miraculin in crude state or denatured, non-reduced miraculin in pure form is a dimer of the peptide. Both tetramer miraculin and native dimer miraculin in crude state had the taste-modifying activity. PMID- 1911855 TI - Amino acid sequence analysis of the beta- and gamma-subunits of eukaryotic initiation factor eIF-2. Identification of regions interacting with GTP. AB - By affinity labelling using two different GTP photoaffinity analogues we previously demonstrated that both the beta- and gamma-subunits of eukaryotic initiation factor eIF-2 are involved in GTP binding (Bommer, U.-A. and Kurzchalia, T.V. (1989) FEBS Lett. 244, 323-327). We have now applied the same method in combination with CNBr cleavage and microsequence analysis in order investigate which part of the polypeptide chain of eIF-2 beta is in close contact to the bound GTP. From the three main CNBr fragments of eIF-2 beta, the C terminal one was found to be labelled by the applied GTP photoaffinity analogue, Guo(2',3'-TDBH)ppp. Because the cDNA sequence of the gamma-subunit of eIF-2 has not yet been published and because cDNA sequence analysis of eIF-2 beta revealed only two out of three consensus sequence elements of a GTP-binding domain, we also sequenced the CNBr fragments of eIF-2 gamma. In this way, sequences containing about 50 amino acid residues were obtained. Taken together with the recently published N-terminal sequences of tryptic peptides of eIF-2 gamma from pig liver (Suzuki et al. 1990, J. Biochem. 108, 635-641), about 30% of the total sequence is now known. One of the CNBr fragments from rabbit eIF-2 gamma contains a sequence (AXXAXXGK) which in several respects resembles that of the consensus sequence element absent from the beta-subunit. PMID- 1911856 TI - Binding of retinoids and beta-carotene to beta-lactoglobulin. Influence of protein modifications. AB - The binding of retinol, retinyl acetate, retinoic acid and beta-carotene to native, esterified and alkylated beta-lactoglobulin was followed by quenching of tryptophan fluorescence. Three studied retinoids bind to native or modified beta lactoglobulin in 1:1 molar ratios, with apparent dissociation constants in the range of 10(-8) M. The maximum tryptophan fluorescence quenching of unmodified beta-lactoglobulin by beta-carotene is observed at the ligand/protein ratio of 1:2. Esterification and alkylation of beta-lactoglobulin shift the ratio of beta carotene/protein to 1:1. In all the cases, except for retinoic acid binding to N ethyllysyl-BLG, the performed chemical modifications of beta-lactoglobulin enhance protein binding affinity. Measured apparent dissociation constants of beta-carotene complexes with native and modified beta-lactoglobulin are an order of magnitude lower from binding constants of other studied retinoids. PMID- 1911857 TI - The formation of complexes between human plasminogen activator inhibitor-1 (PAI 1) and sodium dodecyl sulfate: possible implication in the functional properties of PAI-1. AB - The effect of the anionic detergent sodium dodecyl sulfate (SDS) on human PAI-1 present in plasma, platelet extracts and endothelial cell cultures, was examined. Using the dye partitional extraction method of Mukerjee [1956) Anal. Chem. 28, 870-873) to quantitate ionic surfactants, and a discontinuous spectrophotometric assay for the titration of PAI-1 based on the measurement of residual active t PA, we found (i) that SDS remains tightly bound to PAI-1 after equilibrium dialysis and (ii) that the activity of the latter was closely related to the amount of SDS carried over by the PAI-1 solution. The highest concentrations of SDS (ratio of SDS to protein greater than 0.1) were detected in the platelet derived sources of PAI-1 which also showed the lowest residual t-PA activity. Moreover, it is demonstrated by SDS-PAGE and autoradiography that the tight binding of SDS to PAI-1 decreases its ability to form complexes with t-PA. Similar results were obtained with PAI-1 previously inactivated at 37 degrees C: the inability of PAI-1 to form complexes with t-PA was unchanged after SDS treatment. These observations suggest that the decrease in the residual activity of t-PA observed with the SDS-treated PAI-1 preparations is not related to an increase in the inhibitory activity of PAI-1. In fact, SDS was able to produce a decrease in both the binding of t-PA to fibrin and the activation of plasminogen by fibrin-bound t-PA. Bovine PAI-1 has been shown to exist in a latent SDS activatable form. Our data indicate that such a form might not be present in the human sources of PAI-1 we have tested. PMID- 1911858 TI - Fast heme release from inactive proteins. AB - Kinetics for the release of the prosthetic group from hemoproteins is presented. Heme-protein separation is a biphasic reaction, where an initial phase is significantly faster than the dominant, slow phase. A previous communication concluded that the slow phase represents the active protein. This communication presents data for porphyrin release which shows that the initial fast phase represents an inactive form of the protein. Moreover, we suggest that the fast to slow phase ratio is a sensitive monitor of sample quality for many hemoproteins and that an extrapolation of the slow phase absorbance leads to new estimates for the true physical parameters of unperturbed proteins. PMID- 1911859 TI - Chemical modification of bovine pancreatic deoxyribonuclease with phenylglyoxal- the involvement of Arg-9 and Arg-41 in substrate binding. AB - The inactivation of bovine pancreatic DNase by phenylglyoxal exhibits pseudo first-order and pH-dependent kinetics. At 13.2 mM phenylglyoxal and 25 degrees C, the half-life of DNase is 8 min at pH 8.0 and 2 h at pH 6.7. Calcium, which binds to DNase, does not protect against or facilitate the reaction of DNase with the reagent. However, due to DNA-DNase interaction the half-life of DNase is approx. doubled in the presence of 0.2% (w/v) DNA. Modified DNase has apparently lost its ability to interact with DNA since it elutes behind native DNase on a Sepharose 4B column developed with buffer containing DNA. Complete inactivation of the enzyme is achieved when approx. 4 of the 12 arginines in DNase are modified at pH 6.7. The identification of the radioactive peptides, isolated from the proteolytic digest of [7-14C]phenylglyoxal-treated DNase, showed the four modified arginines to be Arg-9, -27, -30 and -41. Based on the data from dual labeling experiments using a mixture of DNase modified (without DNA protection) by radioactive phenylglyoxal and DNase modified (with DNA protection) by cold phenylglyoxal, it is concluded that Arg-27 and Arg-30 are essentially un protected by DNA while Arg-9 and Arg-41 are protected part of the time. This conclusion agrees with the proposed substrate binding site in the three dimensional structure of DNase (Suck, D., Lahm, A. and Oefner, C. (1988) Nature 332, 464-468) where Arg-9 and Arg-41 are among the residues responsible for interaction with DNA. PMID- 1911860 TI - The lactate dehydrogenase of the icefish heart: biochemical adaptations to hypoxia tolerance. AB - Cardiac lactate dehydrogenase from the hemoglobin- and myoglobin-free antarctic icefish has been purified by affinity chromatography. Structural and kinetic properties of the enzyme were found close or identical to those of its skeletal muscle counterpart and other M-type lactate dehydrogenases. A model involving a dual oxidative-anaerobic metabolism of the icefish heart is proposed. PMID- 1911861 TI - Purification and characterization of thymidine kinase from regenerating rat liver. AB - Thymidine kinase (EC 2.7.1.21) from regenerating rat liver has been purified 70,000-fold to apparent homogeneity by affinity chromatography. Molecular weight of the native enzyme was found to be about 54,000, as determined by gel filtration. Electrophoresis in polyacrylamide gels containing sodium dodecyl sulfate yielded a single band with a molecular weight of 26,000, suggesting that thymidine kinase is a dimer of very similar or identical subunits. The Michaelis constant for thymidine is 2.2 microM. ATP acts as a sigmoidal substrate with a 'Km' of 0.2 mM. Reaction kinetics and product inhibition studies reveal the enzymatic mechanism to be sequential. PMID- 1911862 TI - Cholesterol transport between cells and high-density lipoproteins. AB - Various types of studies in humans and animals suggest strongly that HDL is anti atherogenic. The anti-atherogenic potential of HDL is thought to be due to its participation in reverse cholesterol transport, the process by which cholesterol is removed from non-hepatic cells and transported to the liver for elimination from the body. Extensive studies in cell culture systems have demonstrated that HDL is an important mediator of sterol transport between cells and the plasma compartment. The topic of this review is the mechanisms that account for sterol movement between HDL and cells. The most prominent and easily measured aspect of sterol movement between HDL and cells is the rapid bidirectional transfer of cholesterol between the lipoprotein and the plasma membrane. This movement occurs by unmediated diffusion, and in most situations its rate in each direction is limited by the rate of desorption of sterol molecules from the donor surface into the adjacent water phase. The net transfer of sterol mass out of cells occurs when there is either a relative enrichment of sterol within the plasma membrane or a depletion of sterol in HDL. Recent studies suggest that certain minor subfractions of HDL (with pre-beta mobility on agarose gel electrophoresis and containing apoprotein A-I but no apo A-II) are unusually efficient at promoting efflux of cell sterol. To what extent efflux to these HDL fractions is balanced by influx from the lipoprotein has not yet been established clearly. The prevention and reversal of atherosclerosis require the mobilization of cholesterol from internal (non-plasma membrane) cellular locations. To some extent, this may involve the retroendocytosis of HDL. However, most mobilization probably involves the transport of internal sterol to the plasma membrane, followed by desorption to extracellular HDL. Several laboratories are investigating the transport of sterol from intracellular locations to the plasma membrane. Studies on biosynthetic sterol (probably originating mostly in the smooth endoplasmic reticulum) suggest that there is rapid transport to the plasma membrane in lipid-rich vesicles. Important features of this transport are that it bypasses the Golgi apparatus and may be positively regulated by the specific binding of HDL to the plasma membrane.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1911863 TI - Interaction of low-density lipoproteins with gangliosides. AB - The ganglioside uptake capacity of human serum low-density lipoproteins (LDL), the mode of ganglioside-LDL binding, and the influence of gangliosides on the floatation properties, size distribution, stability and fluorescence of LDL were investigated. The data obtained suggest that both hydrophobic and electrostatic forces are involved in formation of ganglioside-LDL complexes, but the former appear to be more important. Although association of gangliosides with LDL is predominantly unspecific, nonsaturable, and weak, a small saturable component due to specific ganglioside-apolipoprotein binding, also appears to be involved. In the presence of gangliosides the lipoprotein particles aggregate, the intrinsic fluorescence of LDL and their interaction with antibodies against apo-B change indicating that the state of apo-B [corrected] is modified by gangliosides. PMID- 1911864 TI - Apolipoprotein-specific populations in high density lipoproteins of human cord blood. AB - High density lipoproteins (HDL) in human cord blood have previously been shown to exhibit particle size profiles distinctly different from those of adult HDL. The adult HDL profile is comprised of separate contributions from two major apolipoprotein-specific populations; one population contains both apolipoproteins AI and AII (HDL(AIwAII], while the other has apolipoprotein AI without AII (HDL(AIw/oAII]. The present studies establish that cord blood HDL are also comprised of HDL(AIwAII) and HDL(AIw/oAII) populations whose particle size profiles closely reflect cholesterol and HDL-cholesterol levels in cord blood. Compared with the adult, cord blood HDL(AIwAII) profiles generally show both a greater subspeciation within HDL2a and HDL3b/3c size intervals as well as relative reduction of material in the HDL3a interval. In the cord blood HDL(AIw/oAII) profile, HDL2b(AIw/oAII) particles also show subspeciation with a major component that is consistently larger than that normally observed in the adult (11.2 vs. 10.3 nm). As in the adult, the HDL3a(AIw/oAII) component is present but, unlike the adult, its relative amount is low; hence, its peak is usually not discernable in the cord blood total HDL profile. Our studies show that the larger-sized HDL2b(AIw/oAII) of cord blood are enriched in phospholipid which probably accounts for their increased size. The protein moiety of the larger-sized HDL2b(AIw/oAII) has a molecular weight equivalent to four apolipoprotein AI molecules per particle similar to the normal-sized adult subpopulation. Phospholipid enrichment of cord blood HDL(AIwAII) subpopulations within the HDL2a size interval was not observed. However, the protein moiety of cord blood HDL2a(AIwAII) is unusual in that it exhibits an apolipoprotein AI:AII molar ratio considerably lower (0.8:1 vs. 1.6:1) than that of adult. We suggest that the unique particle size distribution of cord blood total HDL is due in large part to: (a) a specific enrichment of phospholipid in HDL2b(AIw/oAII) species, producing particles larger than normal adult counterparts and (b) an elevated proportion of apoAII carried by the HDL(AIwAII) particles that may influence subspeciation in the HDL3a/b/c size interval. PMID- 1911865 TI - Compartmentalization of cholesterol metabolism and cellular growth in cultured intestinal crypt cells. AB - Growth of rat intestinal crypt derived cells IEC-6 ceased when the key enzyme of cholesterol synthesis, hydroxymethylglutaryl-CoA reductase, was blocked by the competitive inhibitor mevinolin. This effect was reversed by the addition of mevalonolactone. LDL suppressed reductase activity as well as cholesterol synthesis from [14C]octanoate and stimulated acyl-CoA cholesterol acyltransferase, but failed to support cell growth despite rapid receptor mediated degradation even in the presence of low mevalonolactone concentrations. Inhibition of cholesterol esterification by Sandoz-Compound 58-035 enhanced cell growth in the presence of mevinolin, but did not promote proliferation in the additional presence of low-density lipoproteins. HDL3 but not HDL2 or tetranitromethane-modified HDL3 totally reversed the mevinolin induced inhibition of cell growth. This rescue by HDL3 was overcome by an increased dose of mevinolin. HDL3 derepressed reductase, stimulated cholesterol synthesis and reduced cholesterol esterification, but did not reverse the cholesterol synthesis inhibition by mevinolin. It is concluded that IEC-6 cells preferentially use endogenously synthesized cholesterol for membrane formation rather than low density lipoprotein cholesterol. High-density lipoproteins appear to normalize cell growth in the presence of mevinolin by inhibition of cholesterol esterification and probably by inducing the formation of non sterol products of mevalonate. PMID- 1911866 TI - Inactivation of pancreatic and gastric lipases by THL and C12:0-TNB: a kinetic study with emulsified tributyrin. AB - THL is a potent inhibitor of pancreatic (PPL) and gastric (HGL, RGL) lipases. Inactivation occurs preferentially at the oil/water interface (method B, C). In the aqueous phase (method A), the inhibition of HGL was accelerated by the presence of bile salts. C12:0-TNB, a disulfide reagent, specifically inactivates gastric lipases and had no effect on the pancreatic lipase (in the presence of bile salts) whatever the method used. The capacity of THL and C12:0-TNB to inactivate lipases using Methods B and C was found to depend directly upon the interfacial area of the system used. Consequently, inactivation can be reduced or prevented by further addition of a water-insoluble substrate which reduces the surface density of inactivator molecules. With a heterogeneous system of this kind, typical of lipolysis, the use of a classical Michaelis-Menten model is irrelevant and hence the traditional kinetic parameters (Km, KI, Vmax) are only apparent values. PMID- 1911867 TI - On the mechanism of stimulation of cholesterol 7 alpha-hydroxylase by dietary cholesterol. AB - In agreement with previous work, treatment of rats with cholesterol, 2% in diet, stimulated the cholesterol 7 alpha-hydroxylase activity more than 2-fold. With less than 1% in diet, no significant effect was obtained. Intravenous infusion of cholesterol-enriched Intralipid had no stimulatory effect. In accordance with some recent work by other groups, it was shown that the stimulation of the cholesterol 7 alpha-hydroxylase by dietary cholesterol was associated with elevated levels of mRNA corresponding to the enzyme. Most of the stimulation of the activity induced by dietary cholesterol could not be prevented by lymphatic drainage. Feeding lymph fistulated rats with 2% cholesterol in diet stimulated the cholesterol 7 alpha-hydroxylase almost 2-fold, indicating that under the conditions employed, a major part of the cholesterol-induced stimulation of the activity was due to factor(s) unrelated to the flux of cholesterol from the intestine to the liver. There was a good correlation between the amount of cholesterol excreted in faeces and the activity of the cholesterol 7 alpha hydroxylase. The half-life of intraperitoneally administered labelled cholic acid was significantly shorter in rats treated with 2% cholesterol in diet (t1/2 = 1.2 +/- 0.1 days) than in control rats (t1/2 = 1.9 +/- 0.18 days). A notable finding was that the weight of faeces was considerably higher in rats fed cholesterol than in the controls. It is hypothesized that a high dietary load of cholesterol causes increased binding of bile acids in the intestine and increased loss of bile acids in faeces. This leads to a reduced suppression of the cholesterol 7 alpha-hydroxylase by the bile acids. The results support the contention that the flux of bile acids rather than the flux of cholesterol from the intestine is the major direct regulator of bile acid biosynthesis. PMID- 1911868 TI - Effects of exogenous apo E-3 and of cholesterol-enriched meals on the cellular metabolism of human chylomicrons and their remnants. AB - The effects of exogenous apo E-3 and of cholesterol-enriched meals on the binding, cell association and proteolytic degradation of human chylomicrons and their remnants were determined in cultured human skin fibroblasts. Chylomicrons were prepared from plasma of normolipemic humans 4 h after a fat meal with normal or high cholesterol content. Remnants were obtained after incubation of chylomicrons with lipoprotein lipase in vitro. Cellular metabolism of chylomicrons was minimal, less than 10% that of LDL. Exogenous apo E-2 enhanced chylomicron metabolism by 3-4-fold. The cellular metabolism of remnants was 2.5 3.5-fold higher as compared to intact chylomicrons but their response to exogenous apo E-3 was considerably lower. The cellular metabolism of chylomicrons and chylomicron remnants obtained from subjects eating cholesterol-enriched fat meal was the highest either without or with added exogenous apo E-3. Yet, even in the preparation that exhibits the highest metabolic activity (apo E-3 enriched remnants from cholesterol-enriched meals) the absolute proteolytic degradation was about two-thirds that of LDL. We conclude that although LDL-receptors take up and degrade chylomicron remnants, the rate of catabolism of remnants by this route can not explain the rapid and complete remnant removal process as observed in vivo. PMID- 1911869 TI - Effects of cholestanol feeding on corneal dystrophy in mice. AB - A cholestanol-enriched diet administered for 8 months to BALB/c mice produced in 20% two kinds of corneal opacities resembling calcific band keratopathy and Schnyder's crystalline dystrophy in humans. The concentrations of cholestanol in serum, liver and cornea of the corneal opacity bearing mice were 30-40-times higher than those of normal mice. On the other hand, brain cholestanol level increased only 7-times in the opacity group as compared with that of control group. There was no significant difference in the cholesterol concentrations of serum and several tissues among opacity, non-opacity and the control group. The crystal particles were observed between epithelial basement membrane and superficial stroma by the electron microscopy. Energy dispersive analysis of the particles revealed that the deposits were composed principally of calcium and phosphorus with other crystalline materials, which was presumed to be cholestanol. These results suggest that the cholestanol may deposit in the cornea from elevated serum levels. Deposition of cholestanol in cornea and related area may be a cause of corneal dystrophy in CTX. PMID- 1911870 TI - Synthesis of nuclear lipids in L2C leukemic lymphocytes. AB - We previously reported that propiconazole strongly inhibits cholesterol synthesis, but not cell division in a stimulated cell, the human lymphocyte cultured with phytohemagglutinin, showing that newly synthesized cholesterol is not necessary for cell division. In this study we labeled the L2C leukemic guinea pig lymphocyte, a naturally stimulated cell, with [2-14C]acetate, and compared the composition of newly synthesized lipids isolated from nuclei and whole cells (or microsomes). We observed that the proportion of cholesterol in labeled non saponifiable lipids extracted from nuclei was lower than in non-saponifiable lipids isolated from whole cells, whereas the proportion of squalene and polar lipids was higher. By analyzing total lipid extracts, the polar lipids were identified as alkylglycerols, and the above mentioned distribution of constituents was confirmed. The identification of alkylglycerols was also supported by the comparison of radioactive lipid composition after labeling cells with three different lipid precursors: [2-14C]mevalonate, [2-14C]acetate and [2 14C]stearate. When cells were labeled in the presence of dodecylimidazole, the percentage of squalene and alkylglycerols decreased in nuclear lipids, but was not altered when cells were cultured in the presence of propiconazole, a cholesterol synthesis inhibitor which does not affect cell division of human stimulated lymphocytes. We have shown that dodecylimidazole inhibited alkylglycerol biosynthesis and squalene uptake by the nucleus, suggesting that these compounds could play a role in the regulation of cell division. PMID- 1911871 TI - Extensive incorporation of dietary delta-5,11,14 eicosatrienoate into the phosphatidylinositol pool. AB - The acyl composition of phosphatidylinositol (PI) is remarkably resistant to dietary fatty acid modification. To investigate the basis of this selectivity, we have probed fatty acids lacking the usual methylene interrupted double bonds. When mice were fed delta-5,11,14 20:3 as 3% of total lipid, this fatty acid, lacking the delta-8 double bond essential for eicosanoid synthesis, replaced a significant quantity of 20:4 (n-6) in PI, but not PC and PE. By altering the acyl composition of PI, novel second messengers may be formed. This fatty acid structure thus provides a unique nutritional tool for investigating the basis of PI acyl specificity, and for determining the metabolic consequences of acyl alteration, in vivo. PMID- 1911872 TI - A proportion of rat liver mitochondrial carnitine palmitoyltransferase can be made activatable by malonyl-CoA. AB - Treatment of rat liver mitochondrial membranes with cholate yields a soluble extract containing carnitine palmitoyltransferase (CPT) activity that is insensitive to malonyl-CoA. As found previously (I. Ghadiminejad and D. Saggerson (1990) FEBS Lett. 269, 406-408), addition of polyethylenen glycol 6000 (PEG 6000) to this extract conferred sensitivity to malonyl-CoA on the CPT. It is now shown that a sub-population of the CPT activity which is sedimentable at 7000 x g after addition of PEG 6000 is activated by malonyl-CoA, whereas the remainder is inhibited by malonyl-CoA. The presence of KCl increases the proportion of the activatable form of CPT. Possible physiological significance of this finding is discussed. PMID- 1911873 TI - Oxidation of very-long-chain fatty acids in rat brain: cerotic acid is beta oxidized exclusively in rat brain peroxisomes. AB - We studied the effect of sodium 2-[5-(4-chlorophenyl)pentyl]oxirane-2-carboxylate (POCA), a potent inhibitor of mitochondrial carnitine palmitoyltransferase I, on fatty acid oxidation by rat brain cells. In cultured glial cells as well as in dissociated brain cells from adult rats palmitic acid (16:0) oxidation was inhibited by about 85% of control values when 25 microM POCA was added to the medium, whereas no inhibition of cerotic acid (26:0) oxidation was observed. Furthermore, omission of carnitine from the culture medium resulted in a 57.7% decrease in palmitic acid oxidation in cultured glial cells, whereas cerotic acid oxidation was not influenced. These results indicate that rat brain peroxisomes contribute only little (about 15%) to palmitic acid oxidation and provide conclusive evidence that cerotic acid is oxidized exclusively in rat brain peroxisomes. PMID- 1911874 TI - Differences in lipogenesis in tissues of control and gold-thioglucose obese mice after an isocaloric meal. AB - Lipogenesis was measured in 2 and 5 week gold-thioglucose (GTG) obese mice after a single meal of 0.5 g of standard chow. Compared to control mice the rate of lipogenesis in GTG obese mice, was 4-fold higher in liver and 10-fold higher in white adipose tissue (WAT). In brown adipose tissue (BAT) of GTG-injected mice the lipogenic rate was only 50% of that of controls. These results indicate that the increased lipid synthesis observed in GTG-injected mice is not due solely to hyperphagia and that some other stimuli, such as increased basal insulin levels and/or decreased thermogenesis and insulin resistance in BAT, contribute to the high rates of fat synthesis in this animal model of obesity. PMID- 1911875 TI - Activation of intracellular calcium-activated neutral proteinase in erythrocytes and its inhibition by exogenously added inhibitors. AB - Intracellular calcium-activated neutral proteinase (CANP) in rabbit erythrocytes was activated by an influx of Ca2+ into the cells. The catalytic large subunit changed from the original 79 kDa from to the 77 kDa and 76 kDa forms on activation just in the same manner as occurs in the autolytic activation of purified CANP in vitro. The activation required both extracellular Ca2+ and A23187, and was accompanied by the degradation of some membrane proteins and morphological changes in erythrocyte shape from discocytes to echinodisks, echinocytes, and spherocytes. Exogenously added Cbz-Leu-Leu-Leu-aldehyde inhibited the activation of intracellular CANP as well as the degradation of membrane proteins and the morphological changes indicating that the latter two processes are due to the action of CANP. Leupeptin and E64d were without effect on intracellular CANP. PMID- 1911876 TI - Deoxyadenosine triphosphate acting as an energy-transferring molecule in adenosine deaminase inhibited human erythrocytes. AB - Deoxyadenosine triphosphate (dATP) is present in adenosine deaminase (ADA) deficient or ADA-inhibited human red cells and in the red cells of the opossum Didelphis virginiana. In order to investigate the functions of dATP in the red cell, red cells were treated with 2'-deoxycoformycin (dCf), a powerful inhibitor of ADA, and incubated with phosphate, deoxyadenosine and glucose. These red cells in which ATP was almost completely replaced by dATP, had the same shape, lactate production, nucleotide consumption, stability of reduced glutathione, osmotic fragility and cell deformability as red cells containing ATP. Cells merely depleted of ATP showed reduced viability. This indicates that dATP compensates well for the absence of ATP and acts as an energy-transferring molecule to maintain cell viability. These results indicate that the accumulation of dATP or the reduction of ATP is not the cause of the hemolysis observed after dCf administration. PMID- 1911877 TI - Evidence for the involvement of endogenous thymidine in the density-inhibition of tumorigenic Chinese hamster V79 cells. AB - Two distinct low-molecular-weight growth inhibitory activities were isolated from supernatants of a density-inhibited, tumorigenic V79 Chinese hamster cell line. By chromatographic analyses, one of these was purified to homogeneity and eventually proved to be thymidine (dThd). In order to investigate the biological role of dThd in a density-inhibited culture of these cells, a dThd-kinase deficient (TK-) clone resistant to the excess of dThd was isolated from V79 cells and the effect of the supernatants on growth of these TK- or TK-proficient (TK+) cells was examined. As a result, the growth of TK- cells was not inhibited but enhanced by the supernatant at the concentrations which significantly inhibited the growth of TK+ cells. Such TK-dependent differential responses to supernatants suggest the presence of deoxyribonucleosides including a high level of dThd in the supernatants. Since it is unlikely that dThd might derive from denatured DNA of dead cells, an accumulation of endogenous dThd in confluent culture appears to be responsible for dThd triphosphates which are synthesized de novo, degraded and excreted into the medium rather than incorporated into DNA as a consequence of aberrant growth in the presence of certain growth inhibitors produced by density inhibited V79 cells. PMID- 1911878 TI - Evidence for direct coupling of primary agonist-receptor interaction to the exposure of functional IIb-IIIa complexes in human blood platelets. Results from studies with the antiplatelet compound ajoene. AB - Ajoene, (E,Z)-4,5,9-trithiadodeca-1,6,11-triene 9-oxide, is a potent antiplatelet compound isolated from alcoholic extracts of garlic. In vitro, ajoene reversibly inhibits platelet aggregation as well as the release reaction induced by all known agonists. In this paper we show that ajoene has a unique locus of action, that is not shared by any other known antiplatelet compound. For example, ajoene inhibits agonist-induced exposure of fibrinogen receptors, as well as intracellular responses such as activation of protein kinase C and the increase in cytoplasmic free calcium induced by receptor-dependent agonists (collagen, ADP, PAF, low-dose thrombin). On the other hand, with agonists that can by-pass (at least partially) the receptor-transductor-effector sequence, such as high dose thrombin, PMA, NaF, only the exposure of fibrinogen receptors is blocked by ajoene. Binding of fibrinogen to chymotrypsin-treated platelets is only slightly inhibited by ajoene. The results reported here also show that: (a) ajoene does not act as a calcium chelator, does not impair the initial agonist-receptor interaction and does not influence the basal levels of intracellular inhibitors of platelet activation such as cyclic GMP; (b) the locus of action of ajoene is a yet unknown molecular step that links, in the case of physiological agonists, specific agonist-receptor complexes to the sequence of the signal transduction system on the plasma membrane of platelets. In the case of non-physiological, receptor-independent agonists (PMA, NaF), we can only speculate on the hypothesis that they somehow mimic the effect of the agonist-receptor complexes on the signal transduction system; and (c) the exposure of fibrinogen receptors is not a direct consequence of other intracellular processes. These observations clearly show, for the first time, that the exposure of fibrinogen receptors is a membrane event proximally and obligatorily coupled to the occupancy of other membrane receptors by their agonists without any intervention by the cytoplasmic biochemical processes. Additional results support the involvement of G-proteins in these early events of platelet activation. Furthermore, a role of the beta tau subunits of G-proteins in the exposure of fibrinogen receptors is proposed. PMID- 1911879 TI - Changes of lysosomal proteinase activities and their expression in rat cultured keratinocytes during differentiation. AB - The cathepsins B, H and L, lysosomal cysteine proteinases, play a major role in intracellular protein degradation. These proteinase activities and expressions were examined in a Ca2+ regulated epidermal culture system which consists of two morphological cell types: undifferentiated cells grown in low Ca2+ (0.1 mM concentration) and differentiated cells grown in high Ca2+ (1.8 mM concentration), respectively. Cathepsin B and L activities of the differentiated cells showed a several-fold increase compared to that of the undifferentiated cells. In addition, by using CM-cellulose column chromatography, cathepsin B and L were separated and the level of cathepsin L activity increased significantly. Cathepsin B, L and H were also detected by using an immunoblotting procedure in which their bands were expressed after differentiation was induced by the increasing calcium concentration. Cathepsin L activity and immunostaining intensity reached a maximum at 1 or 2 days of differentiation. In contrast, cystatin alpha (an endogenous inhibitor of cysteine-dependent cathepsins) appeared in the final stage of differentiation. These results indicate that the expression of epidermal cathepsins and their endogenous inhibitor are involved in part of the program of cell differentiation and the terminal differentiation process in cultured rat keratinocytes. PMID- 1911880 TI - Factors influencing variable oxidative hemolysis of inbred mouse erythrocytes. AB - The hemolysis of erythrocytes from certain inbred mouse strains (e.g., BALB/c) in response to hydrogen peroxide stress has been shown to be correlated with the type of hemoglobin beta chain (Kruckeberg, W.C., et al. (1987) Blood 70, 909 914). The characteristic hemolytic response of BALB/c red cells to oxidative stress resembles that of human red cells in that carbon monoxide and iron chelators inhibit hemolysis of both. Gross hemoglobin oxidation rates were similar in hemolytic (BALB/c) and nonhemolytic (C57BL/6) strains. The rate and degree of in vitro catalase inhibition by sodium azide was also the same for the two strains. Even in the presence of this catalase inhibitor the assayable hydrogen peroxide disappeared within seconds of its addition, yet hemolysis was not observed for about 15 min. The mechanism underlying this delay between hydrogen peroxide addition and disappearance and subsequent hemolysis is under investigation. PMID- 1911881 TI - Inhibition of depolarisation-induced calcium influx into GH3 cells by arachidonic acid: the involvement of protein kinase C. AB - The influx of 45Ca2+ induced in GH3 cells by exposure to 60 mM K+ medium was inhibited by arachidonic acid (AA) in a concentration-dependent manner. This action of AA was not prevented by inhibitors of its metabolism but was reversed by the inhibitors of protein kinase C (PKC), H7 and staurosporine but not their less active congeners HA 1004 and K252a, respectively. Presumed down-regulation of PKC by pretreatment with phorbol 12,13-dibutyrate (PDBu) also greatly diminished the effect of AA. Experiments to assess effects of AA on 45Ca2+ efflux and on cytosolic Ca2+ concentrations indicated that an additional PKC-independent action of AA involving the release of intracellularly stored calcium was present. Both direct activation of certain PKC isoform(s) by AA and the synergistic influence on PKC activity by its concomitant raising of intracellular Ca2+ concentrations, may be physiologically important in the regulation of depolarisation-induced Ca2+ entry. PMID- 1911882 TI - Modulation of the exocytotic reaction of permeabilised rat mast cells by ATP, other nucleotides and Mg2+. AB - In the terminal stages of exocytosis from permeabilised mast cells, ATP has a number of modulatory actions, although its presence (and by implication, phosphorylation) is not obligatory for secretion to occur. These effects include (1) the enhancement of the sensitivity to both of the essential effectors (Ca2+ and guanine nucleotide); (2) the maintenance of the responsiveness of permeabilised cells; (3) restoration of responsiveness to cells rendered refractory by previous permeabilisation, and (4) induction of delays in the onset of exocytosis from permeabilised cells. We define the modulatory reactions induced by ATP by characterising their specificity to other potential phosphorylating nucleotides and their requirement for Mg2+. GTP and AppNHp are without effect in any of the modulatory actions. ATP, ATP-gamma-S, ITP, XTP, CTP and UTP all appear to support an enhancement of the sensitivity to GTP-gamma-S when applied immediately at the time of permeabilisation. However, the non adenine nucleoside triphosphates appear to mediate their effect by transphosphorylation to ADP, and therefore the active species appears to be ATP. Only ATP is capable of maintaining and restoring responsiveness (2 and 3 above). Only ATP and ATP-gamma-S induce onset delays and do so moreover in the absence (less than 10(-8) M) of Mg2+. We conclude that three of the modulatory effects (1, 2 and 3 above) which all express a requirement for Mg2+, and can be prevented by inhibitors of protein kinase C are likely to result from phosphorylation reactions. The induction of delays by ATP is unlikely to incur phosphorylation. PMID- 1911883 TI - Transformation and amplification of the K-fgf proto-oncogene in NIH-3T3 cells, and induction of metastatic potential. AB - A plasmid containing the K-fgf proto-oncogene linked to the dihydrofolate reductase gene has been constructed, and used in transfection experiments to investigate the effects of K-fgf expression on the tumorigenic and metastatic properties of NIH-3T3 fibroblasts. Analysis of cells transfected with K-fgf revealed that expression of the K-fgf proto-oncogene can, in a single step, induce both tumorigenic and metastatic characteristics, as determined in soft agar cloning experiments, and in tumorigenicity and experimental lung metastasis assays with BALB/c nu/nu mice. Selection for resistance to increasing concentrations of methotrexate lead to the isolation of a series of cell lines containing amplifications of both the dihydrofolate reductase gene and the linked K-fgf gene, which synthesized elevated levels of growth factor message and protein. The most highly resistant and gene amplified cell lines exhibited lower than expected levels of K-fgf mRNA, and also appeared to have down-regulated cell surface growth factor receptors. Further support for the concept that altered K fgf expression can induce fully malignant and metastatic cells was obtained in experimental metastasis assays, where K-fgf transfected and gene amplified cell lines were highly aggressive. PMID- 1911884 TI - Reduced growth of Ehrlich ascites tumor cells in creatine depleted mice fed beta guanidinopropionic acid. AB - The effect of implantation of Ehrlich ascites tumor (EAT) cells on creatine distribution was investigated. It was also studied how depletion of creatine by feeding creatine-analogue beta-guanidinopropionic acid (beta-GPA) affects the growth of EAT cells in mice. Enhanced mobilization of creatine from host tissues to EAT cells against a greater concentration gradient was observed. The creatine (but not creatinine) level in blood plasma was lowered to 22% of the normal value by beta-GPA feeding alone and assimilation of 14C-creatine into EAT cells was inhibited. The growth of EAT cells was significantly reduced and the duration of survival of mice after implantation of EAT cells was extended when the creatine concentration was decreased. A decrease in daily food consumption and the degree of muscle atrophy after implantation of EAT cells was less in beta-GPA than control groups. In the creatine-depleted mice, the rate of increase in total EAT cell number and the volume of abdominal ascites were approximately half of the control values, and more dead EAT cells were observed. These results suggest that supplementation of beta-GPA inhibits creatine transfer to EAT cells and reduces the growth of cancer cells. PMID- 1911885 TI - The human pyruvate dehydrogenase complex: a polymorphic region of the lipoate acetyl transferase (E2) subunit gene. AB - A major issue in the study of the pathogenesis of primary biliary cirrhosis is whether the E2 subunit of the pyruvate dehydrogenase complex (PDH-E2), the major autoantigen in the disease, exists as a tissue-specific isoform. cDNA clones spanning a segment of the 3'-catalytic region of PDH-E2 (nt 1158-1361) have been isolated from human kidney, placenta and bile epithelium cells. Nucleotide sequence analysis of the clones showed differences consistent with the presence of normal variants of PDH-E2 in the human population. However, the existence of tissue-specific isoforms of PDH-E2 cannot yet be discounted. PMID- 1911886 TI - Conformational energy analysis of the substitution of Val for Gly 233 in a functional region of platelet GPIb alpha in platelet-type von Willebrand disease. AB - Platelet-type von Willebrand disease (PT-vWD) is an autosomal dominant bleeding disorder in which patient platelets exhibit an abnormally increased binding of circulating von Willebrand factor (vWF). We have recently shown that this abnormality is associated with a point mutation resulting in substitution of Val for Gly 233 in platelet membrane glycoprotein Ib alpha (GPIb alpha), a major component of the platelet GPIb/IX receptor for vWF. To investigate the effect of this substitution on the three-dimensional structure of this region of the protein, we have generated the allowed (low energy) conformations of the region of the GPI alpha protein containing residues 228-238 (with 5 residues on either side of the critical residue 233) with Gly 233 (wild type) and Val 233 (PT-vWD) using the computer program ECEPP (Empirical Conformational Energies of Peptides Program). The wild-type sequence is Tyr-Val-Trp-Lys-Gln-Gly-Val-Asp-Val-Lys-Ala. We find that the Gly 233-containing peptide can exist in two low energy conformers. The lowest energy conformer is a structure containing a beta-turn at Gln 232-Gly 233 while the alternative conformation is an amphipathic helical structure. Only the amphipathic helical structure is allowed for the Val 233 containing peptide which contains a hydrophobic 'face' consisting of Val 229, Val 233 and Val 236 and another hydrophilic surface composed of such residues as Lys 231 and Asp 235. No such surfaces exist for the lowest energy bend conformer for the Gly 233-containing peptide, but do exist in the higher energy helical structure. The amphipathic surfaces in the 228-238 region of the Val 233 containing GPIb alpha protein may associate strongly with complementary surfaces during vWF binding to the GPIb/IX receptor complex and may help explain heightened association of vWF with this receptor in PT-vWD. PMID- 1911887 TI - Methionine adenosyltransferase activity in cultured cells and in human tissues. AB - We have investigated methionine adenosyltransferase activity (MAT) in extracts of a variety of normal and malignant human tissues and cultured cell lines. MAT activity assayed from 17 different cultured cell lines varied to a great extent. Ramos (human, Burkitt's lymphoma) and EL4 (mouse, T cell lymphoma) cells showed MAT activity near 300 pmol/mg per min. Daudi (human, Burkitt's lymphoma) and almost all monolayer cells had MAT activity below 100 pmol/mg per min. Human peripheral blood lymphocytes had MAT activity of 36 pmol/mg per min. The MAT activity of the cell lines can be related to doubling time: cell lines with short doubling times have much higher MAT activity than other cell lines. A large variation in MAT activity in different human tissues was observed. In autopsy samples MAT activity was highest in the brain and in the colon. Malignant tissue samples gave much higher MAT activity than normal tissues. Lung cancer (carcinoma squamocellulare pulmonis) had MAT activity of 30.7 pmol/mg per min, while in normal lung it was 2.4 pmol/mg per min. PMID- 1911888 TI - The neuromelanin of the human substantia nigra. AB - The pigment of the human substantia nigra was isolated after extraction of lipids and proteins with 2% sodium cholate in 30% ethanol followed by 2% sodium dodecyl sulfate in 10% glycerol. The pigment was hydrolysed with HI or degraded by treatment with KMNO4 and the samples were examined for compounds known to derive from pheomelanin (4-amino-3-hydroxyphenylalanine, AHP and 4-amino-3 hydroxyphenylethylamine, AHPEA), or from eumelanin (pyrrole-2,3,5-tricarboxylic acid, PTCA). The HI hydrolysis yielded AHPEA in large quantities, indicating cysteinyldopamine as the main source of the pheomelanin moiety of the neuromelanin, but also trace amounts of AHP, derived from cysteinyldopa oxidation products. Dopamine and small quantities of dopa were also obtained by HI hydrolysis of the neuromelanin. The yield of PTCA was low, but the amounts observed show that part of the neuromelanin is of the eumelanin type, a fact compatible with an occasional exhaustion of the glutathione-cysteine reduction system at the site of neuromelanin formation. PMID- 1911889 TI - [Color-coded duplex sonography]. AB - Color Coded Duplex-Sonography (CCD) is the latest development in ultrasound equipment for non-invasive evaluation of the vascular system. Compared to conventional Duplex-Sonography the advantage of CCD is the ease of handling and quicker diagnosis, although there in no significant increase in information with CCD. The main indications for CCD are superficially located circumscribed vascular lesions as in carotid artery stenosis, tumors in the neck, disturbed renal transplant perfusion, hemodialysis vascular access shunts, deep vein thrombosis, testicular torsion and complications following vascular surgery of the extremities. The abdominal applications are limited. PMID- 1911890 TI - [The visual method for inspecting film processing in accordance with Section 16 of the German X-ray Ordinance (the Bavarian alternative). Fundamental principles and initial results]. AB - The visual method is an alternative for examining whether film processing and the x-ray equipment are in accordance with the provisions of subsection 16 of the Federal German X-ray Ordinance (Roentgenverordnung). By this alternative it is possible to dispense with the densitometer and the sensitometer. Workday-to workday or weekly control exposure of the grey scales is performed by means of the x-ray equipment, the dose being maintained at a constant level. The grey scale produced in this manner is compared with a reference scale; this ensures continual monitoring of the dose-density relation. Errors of the apparatus and errors during developing, or of the film, can be recognised separately due to double-sided measurement of the dose (entrance dose of the test sample and exit or film dose). PMID- 1911891 TI - [The diagnostic value of conventional x-ray diagnosis and quantitative mineral measurements in patients with clinical symptoms of osteoporosis]. AB - The problem of differentiating between patients suffering from osteoporosis and those with healthy bones is discussed on the basis of distribution of the age specific and sex-specific mineral salt values in a healthy population and in a population with clinically manifest osteoporosis. By comparing the results of quantitative mineralometry and conventional x-ray films of the human skeleton in a histologically clarified group of persons with clinically manifest osteoporosis signs and symptoms, the diagnostic ranking of both methods is assessed and discussed. PMID- 1911892 TI - [DEXA (dual-energy x-ray absorptiometry) and DPA (dual photon absorptiometry) in densitometry of the femoral neck: correlation of the measurements of three commercially available instruments]. AB - The bone mineral density measurements of three different instruments at the femoral head were compared using 12 cadaver specimens. Two of these instruments were operated by x-rays (dual energy x-ray absorptiometry = DEXA), whereas one system was based on a gadolinium source (dual photon absorptiometry = DPA). Although excellent correlation between the measurements was obtained (r greater than 0,9), the measurements of one of the DEXA-instruments were significantly higher than the measurements of the two other systems. We conclude that a comparison of bone mineral density measurements obtained on different densitometry instruments may pose problems. Follow-up examinations should be done on one single densitometry unit. PMID- 1911893 TI - [A comparison of the visualization of liver metastases using sonography and dynamic computed tomography]. AB - 184 liver metastases in 30 patients were examined retrospectively and the imaging in sonography, dynamic CT and plain CT was compared. Dynamic CT is markedly superior to plain CT and sonography in respect of the delineation of liver metastases, especially also in the identification and location of diffuse metastases. PMID- 1911894 TI - [Diagnostic and therapeutic control of varicoceles using angiodynography]. AB - We report on the results of angiodynography of 21 patients with suspected varicoceles. In 14 cases a varicocele could be diagnosed. Additionally, 19 patients underwent conventional Doppler sonography (16 with positive findings), 7 thereof also a testicular phlebography (5 positive findings). Thus, in conventional Doppler sonography there were 2 false positive findings. With angiodynography it was possible to detect an existing varicocele in all 14 (of the 21) cases even if only a small retrograde flow existed. In 11 of the cases this could be graded with the help of the flow velocity. In case of negative findings in angiodynography, further invasive techniques are unnecessary. However, before embolisation of a varicocele and to show preoperatively vessel variations or collateral vessels, testicular phlebography is still indicated. PMID- 1911895 TI - [The supinator fat line--its visualization and validity]. AB - Based on 259 lateral x-ray films of the elbows of healthy subjects, the typical forms of the fat plane overlying the supinator muscle were determined. The forms of this plane in 121 patients who had suffered bony lesions in the elbow joint region were juxtaposed to these x-ray images. Measurements of the proximal distance between the fat plane and the extended tangent of the anterior humeral cortex layer revealed that distances of more than 13 mm in children and of more than 18 mm in adults are highly suspicious of a fracture. The good visualisation of the fat plane by means of various imaging methods is appropriately demonstrated. PMID- 1911896 TI - [Magnetic resonance tomographic differentiation of eye muscle enlargement. Study technique, characteristic images, literature review]. AB - Multiplanar facilities of MR imaging allow for a detailed analysis of eye muscle enlargement. For taking full advantage of MRI's diagnostic possibilities, thorough knowledge of pathological anatomy is necessary. The paper describes examination technique and criteria for analysis. Diseases leading to eye muscle enlargement are illustrated by exemplary cases. PMID- 1911897 TI - [Initial experiences with the use of gadolinium DTPA in infants and children under 2 years of age]. AB - The use of Gadolinium-DTPA as a paramagnetic contrast agent in MRI with adults and juveniles concerning brain and spinal cord pathology is well proven since years. Tolerance and safety were excellent. In the FRG it is only introduced for children over two years of age. Therefore this report deals with the experience in four infants and small children under the age of two, who received gadolinium DTPA for diagnostic purposes in pre- or post-operative circumstances. They all were suffering from neurological tumors and got additional diagnostic information in three cases. Clinical side-effects like urticaria, vomiting or convulsions had not been observed nor had pathologic changes of the biochemical parameters been noticed. PMID- 1911898 TI - [Diagnosis of a suspected pulmonary embolism in a centrally localized bronchial carcinoma]. AB - Case report of a 57-year old male patient suffering from a central bronchial carcinoma, causing complete unilateral non-perfusion of the left lung (v. Euler Liljestrand reflex). Discussion of the possible diagnostic methods especially on difficulties in differential diagnosis to pulmonary embolisation. PMID- 1911899 TI - Pineal gland and aging. PMID- 1911900 TI - Aging as a consequence of fuel utilization. PMID- 1911901 TI - Effects of a low intensity exercise program on selected physical performance characteristics of 60- to 71-year olds. AB - The effects of a low intensity exercise program on strength, flexibility, balance, gait and muscular endurance were determined in sixty-two 60- to 71-year old men and women. Subjects exercised for 1 hour daily 5 days a week for 3 months. Before and after the exercise program, each participant underwent lower extremity range of motion (ROM) determinations, isometric and dynamic strength testing (Cybex) of the knee and ankle musculature, standing balance tests, a gait examination and a fatigue test for the quadriceps. Thirteen control subjects who did not exercise also were tested at two time periods, 3 months apart. Significant improvements in strength occurred for exercise subjects, particularly at the fastest speed settings on the Cybex. ROM measures of the hip and trunk, and standing balance times improved, but no change in endurance or gait parameters was found. With the exception of muscular endurance, no changes were observed among the controls. Exercise subjects frequently reported improvements in functional capacity and activities of daily living. These results suggest that a low intensity exercise program can improve strength, balance and flexibility in sedentary healthy older people. PMID- 1911902 TI - Methylation status of cKi-ras and MHC genes in rat pituitary glands during aging and tumorigenesis. AB - Methylation patterns of MHC (major histocompatibility complex) class I and vKi ras (viral Kirsten-ras) homologous sequences in normal and adenomatous rat pituitary glands were studied as a function of age by Southern hybridization analysis using the isoschizomers Hpa II and Msp I. Both MHC class I and vKi-ras homologous sequences were found to be hypomethylated in a number of tumors, compared to normal pituitary gland tissue. However, despite reports indicating a general demethylation in mammalian tissues in relation to donor age, age-related methylation changes in this apparently methylation-unstable and cancer-prone organ were not observed. PMID- 1911903 TI - Effect of lifelong hypocaloric diet on discrete memory of the senescent rat. AB - The memory retention abilities of aged rats fed different diets were assessed in two different avoidance tasks. The standard passive avoidance procedure revealed an age-related memory impairment in old rats fed a standard diet (ST), whereas old rats fed a hypocaloric diet (HY) behaved similarly to young animals. To clarify whether this deficit could be attributed only to cognitive decay and not other factors, such as the tendency of old rats to prefer darkness to light more than young and adult animals, a multiple passive avoidance task was performed. This test offers rats the possibility to escape to a dark chamber in which they have never been shocked, and thus provides a means of checking factors other than memory retention abilities. All the old rats showed a more marked preference to escape to darkness compared to young and adult animals. However, senescent animals fed a ST diet had poor memory retention abilities compared to aged animals fed the HY diet, and young and adult rats. The results of this test confirmed the findings of the standard passive avoidance task. PMID- 1911904 TI - Relationships between health behaviour and depression in the aged. AB - Relationships between the occurrence of depression, drinking alcohol, performing physical exercise and smoking were explored in Finns aged 60 years or over. A multivariate analysis based on log-linear models showed a positive relationship between higher occurrence of depression, smoking and no regular physical exercise in men, and between higher occurrence of depression, not smoking, abstaining and no regular physical exercise in women. We suggest that factors related to personality traits and coping styles explain both the relationship between depression and smoking, and sex differences in smoking habits; the relaxing and euphoric effect of a small amount of alcohol may explain the association between lower occurrence of depression and non-abstaining in women. The association between higher occurrence of depression and no regular physical exercise may reflect either the cause of depression, or the effects of depressive disorder. PMID- 1911905 TI - Study of constipation in a geriatric hospital, day hospital, old people's home and at home. AB - A study of constipation and related factors was carried out in 439 geriatric hospital patients, 183 people living in two old people's homes, and 78 patients visiting a geriatric day hospital. In addition, a cross-sectional survey of constipation and related factors was undertaken in 138 people older than 74 years and 74 people aged 41 to 50 years living at home. Constipation and the use of laxatives were most frequent in the geriatric hospital (79% and 76% respectively), followed by the old people's homes (59% and 60%), the day hospital (29% and 31%), elderly living at home (38% and 20%) and middle-aged living at home (12% and 5%). The results suggest an increased risk of constipation for the persons walking less than 0.5 km daily [relative risk (RR) = 1.7], walking with help (RR = 3.4), chairbound (RR = 6.9) and bedbound (RR = 15.9). The relative risk of constipation increased for the persons living in the old people's homes (RR = 1.7) and the geriatric hospital (RR = 2.2), and also with advancing age (between 75 and 84 years, RR = 2.9; over 84 years, RR = 4.9). The prevalence of constipation was directly correlated to fecal and urinary incontinence. PMID- 1911906 TI - Alzheimer's disease, cerebral amyloid angiopathy, and dementia of acute onset. AB - The coexistence of cerebral amyloid angiopathy (CAA) and Alzheimer's disease (AD) should be considered in the differential diagnosis of cases with acute onset of dementia when other causes have been excluded. We report clinical and neuropathological findings in a 78-year-old man who developed dementia of acute onset with an apparent rapid course three months before his death. Postmortem microscopic examination of the brain revealed senile (neuritic) plaques and neurofibrillary tangles in the hippocampus and cerebral cortex. CAA affected vessels of the neocortex and leptomeninges, most severely in the frontal and parietal areas. PMID- 1911907 TI - Changes in heart rhythm power spectrum during human aging. AB - Age-related changes of the major oscillatory components--low-frequency (LFC, 0.02 0.05 Hz), medium-frequency (MFC, 0.08-0.12 Hz) and high-frequency (HFC, 0.2-0.4 Hz)--in the heart rhythm (HR) power spectrum were studied in 256 healthy subjects 20 to 89 years of age. The age factor exerted a considerable effect on the characteristics of the HR power spectrum. The decrease in the total power of the HR power spectrum and in HFC and MFC showed a nonlinear pattern. LFC power showed a linear decrease with aging. In view of the marked decrease in HFC and MFC in the 30- to 59-year age range, the elderly and very elderly subjects demonstrated the prevalence of the LFC contribution to the total HR power spectrum. PMID- 1911908 TI - Accidents in the institutionalized elderly: a risk analysis. AB - Among a total of 4,862 admittances to a Swedish geriatric hospital and its associated nursing homes, 827 accidents occurred in 588 patients during one year. The purpose of the present study was to establish the direct causes of these accidents and to identify possible risk factors. Information was collected from medical records, interviews with patients and staff, examination of the mental and physical state of the patients, and through reconstruction of the accidents. The investigation embraced 270 patients with 308 major accidents (fractures, sprains, open wounds, concussions and injuries to ligaments), and 318 patients with 519 minor accidents (bruises, contusions, abrasions and minor burns). Injury free patients with nearest lower bed number in relation to patients with major accidents formed a control group. Patients with previous injuries, balance disturbances, and polypharmacy were at high risk, and intrinsic factors such as dizziness and impaired balance proved to be more significant as direct causes for the occurrence of accidents than environmental factors. The estimated risk for a patient with all these risk factors to have an accident during one year was 94%. PMID- 1911910 TI - The pineal gland: a circadian or seasonal aging clock? PMID- 1911909 TI - Sleep disturbance and Alzheimer's disease: relationship to behavioral problems. AB - We studied the sleep characteristics of 108 outpatients with probable Alzheimer's disease and found that sleep disturbance was significantly related to daytime behavioral disturbance but not to cognitive impairment. Possible treatment strategies and neuropathological and neurochemical mechanisms are discussed. PMID- 1911911 TI - [Thermodynamic and spectroscopic study of intermolecular association in aqueous dipeptide solutions]. AB - Peculiarities of the concentration dependences of apparent molar heat capacities and volumes of aqueous solutions of dipeptides were considered. Possible interpretation of the character of these dependences on the basis of Gibson and Sheraga's model of solvation shell were shown. Three concentration regions corresponding to the existence of various molecular forms of dipeptides in solution were marked out. PMID- 1911912 TI - [Parameters of enzyme reactions in microcirculation]. AB - It has been shown that time-dependent change in the concentration of enzymic reaction substrate in a microcirculatory channel cell, as well as its steady spatial distribution contain information both about the structure of the microcirculatory channel and about the reaction kinetic parameters. In terms of the hypothesis about the stationary state of the enzyme-substrate complex at selective values of hydrodynamic parameters of the substrate, enzyme, channel correlation between the change in the substrate concentration, its stationary distribution, kinetic parameters and the microcirculation cell structure were estimated. PMID- 1911913 TI - [Solid phase lipid peroxidation and blood hemoglobin oxidation]. PMID- 1911914 TI - [Denatured increments of heat capacity in globular proteins and its connection with vitrification processes]. AB - Absolute values of heat capacity for some hydrated globular proteins have been studied by differential scanning calorimetry (DSC) method. It has been found that for the proteins with completely bound water, like in the case of protein solutions, the value of heat capacity of denatured proteins is higher than that prior to denaturation. Depending on temperature and humidity the denatured proteins can be either in high elastic or glass state. Specific heat capacities for these two states have the same values for all proteins and depend only on temperature with a characteristic increment of 0.55 J/g.K. at glass transition. The glass transitions were observed not only in denatured but also in native proteins. As it follows from our results, the main contribution to the heat capacity increment at denaturation is connected with the thermal motion in the protein globule which is in contrast with the commonly accepted ideas. PMID- 1911915 TI - [Microcalorimetric study of heat denaturation of DNA from calf thymus DNA in the absence of magnesium ions]. AB - Thermal denaturation was studied for a wide range of magnesium ions concentrations and salt concentration 0.15 M NaCl. It was shown that thermal stability of DNA increases at low Mg/2P ratios and decreases at high concentrations of magnesium ions. Up to Mg/2P = 10 DNA denaturation is an equilibrium process. With an increase in magnesium ions concentrations the enthalpy of DNA denaturation reaches the maximum at Mg/2P = 10 (50 kJ/mole base pairs). DNA aggregation and appearance of a new heat absorption peak is observed in the high temperature region at Mg/2P = 10. At this region of magnesium ions concentrations DNA denaturation process is non-equilibrium. PMID- 1911917 TI - [Study of the electrochemical heterogeneity of high density lipoproteins using a lipophilic synthetic anion]. AB - Differential binding of lipophilic permeant anion-tetraphenylboron by high density lipoproteins is shown. The electrochemical heterogeneity of lipoproteins is explained by the difference in their protein-lipid content. PMID- 1911916 TI - [Cotranslational, cosecretory protein folding and its renaturation from a denatured state]. AB - On the basis of the available experimental data on structure, biosynthesis and secretion of globular proteins it is concluded that an alpha-helix is a starting conformation at formation of the native structure of any globular protein (alpha helical model for initiation of protein folding). The structural invariant (clusterization of hydrophobic side chains on the alpha-helix surface) in the amino acid sequences of globular proteins is found which is predicted by alpha helical model for the initiation of protein folding. The model predicts the pyramidization of the atoms C and N of peptide groups during the formation of spatial structure of proteins and a number of other effects that can be put to the experimental test. In the work the mechanism for protein translocation across membrane lipid bilayer is also suggested. PMID- 1911918 TI - [A new concept of the structure of the dual electrical layer on the cell surface under the action of a high concentration electrolyte]. AB - New data are presented describing the characteristics of double electrical layers on the surfaces of cells immersed in high electrolytic solutions. Gel glycosides located at the periphery of halo-forming cells play the key role in forming these structures. PMID- 1911919 TI - [Theoretical analysis of possible types of chronic viral infection of a cellular population]. PMID- 1911920 TI - [Effect of a low frequency electromagnetic field on biological cells]. AB - Possibility of energy of low frequency electromagnetic waves transformation into the energy of multimodules mechanical vibrations of the biological membrane is proved for spherical and cylindrical models of the cell. Formula for calculating the membrane displacement from equilibrium position is derived. PMID- 1911921 TI - [Sensitivity and functional characteristics of modern chemoluminescence meters]. AB - The paper describes the following quantum phenomenon discovered by B. N. Tarusov, A. I. Zhuravlev and A. I. Polivoda in 1961: spontaneous endogenous biochemiluminescence of animal tissues and cells in the spectral range of 320 1100 nm. It initiated studies of the role of electron-excited states and quanta in metabolism, i.e. it started the development of quantum biology of animal organisms. Intensity of this ultra-weak luminescence is determined and its classification is presented according to sensitivity towards fixation ability: a) ultra-weak 10-10(2) quanta/sec (spontaneous luminescence of blood plasma and serum, mitochondria suspension at 37 degrees C); b) ultra-weak 10(2)-10(3) quanta/sec (spontaneous luminescence of lipids and urea at 37 degrees C); weak 10(5)-10(6) quanta/sec (luminol-dependent luminescence of the blood immunocompetent cells, initiated by peroxides and luminescence catalysts in serum, plasma, lipids, suspension of organelles; d) 10(6) quanta/sec and higher (fixed by the eye or photoelement luminescence of glow worms, bacteria or ATP triggered luciferin-luciferase reactions). PMID- 1911922 TI - [Anion-binding centers of human serum albumin during an N-F conformation transition and in isolated albumin and blood serum]. AB - Fluorescent probe N-phenyl-1-amino-8-sulfonaphthalene (ANS) was used for studying pH-dependent structural N-F-transition in human serum albumin of two kinds: in commercial albumin and in natural blood serum. The kinetics of ANS fluorescence decay in albumin solutions was measured. There were found two types of the sites occupied by ANS in albumin under physiological conditions (pH 7.4). In the first binding site ANS fluorescence decay time was 16.6 +/- 0.3 nsec and it was not significantly changed at N-F transition (pH 4.0). In the second binding site the decay time was dependent on pH in commercial albumin and was not significantly changed in serum. In the second binding site there were individual differences of ANS decay time (4.3 +/- 0.6 nsec). The observed ANS fluorescence intensity enhancing (about 40-50%) in N-F transition may be explained by an increase of albumin binding sites capacity for ANS. PMID- 1911923 TI - [Thermotropic changes of certain characteristics of human blood]. AB - Viscosity and spectroscopic characteristics of blood plasma were studied in the temperature range from 0 to 40 degrees C. A correlation between thermotropic anomalies of plasma viscosity at 16-26 degrees C and 32-36 degrees C and a change in certain spectroscopic parameters were reported, which can be related to the re structuring of intermolecular interactions in the system of plasma proteins. PMID- 1911924 TI - [Statistical model of the inherent noise in the visual system]. AB - A concept of intrinsic noise of the visual system has been formulated. It has been shown that the intrinsic noise is realized in the form of the stochastic (from simple chance to complicated pithy) visual images. On the basis of the suggested concept in the limits of a normal approach, taking into account several obvious suppositions, two identical forms have been obtained of representations of probability density of own noise--the mathematical model of own noise. This model includes, as a particular case, the model of Swets, Tanner and Birdsall and has no inherent limitations. PMID- 1911925 TI - [Effect of sizes of the retinal receptive field on the precision of image perception]. AB - A paradox of sharp vision regardless of relatively large receptive fields of the retina is discussed. Transformation of images by the receptive fields or intersecting fields of vision of omma-tidia of the complex eye is described as an approximation of Bool functions by the implicant forms. Such an approximation results in the information compression. The compression coefficient is determined by the ratio between the implicants number and the number of points in the field of determination of the Bool function. The approximation errors strongly depend on the size of the receptive fields. With their increase the error abruptly decreases and only after passing the deep minimum it begins to slowly increase. The mechanism of information compression is a universal one and is similarly realized on the retina, facet and t.v. sets. PMID- 1911926 TI - [Formation model of the electrical potential of skin]. AB - A model of the electrical potential form of the skin was discovered. It contained electrical parameters of the epidermis and sweat glands which were connected with those of the sweat. The formula for the electrical potential of the skin are explained by the base type of man's galvanic skin reaction. PMID- 1911927 TI - [Electrical activity of muscles during disturbances in the trajectory of single joint motion in the arm]. AB - Horizontal "extension-flexion" movement of human arm at the elbow joint was studied. Humans performed movements in accordance with the instruction to ignore sudden trajectory changes that arose by the arm during lengthening of different elastic rods with friction. It was shown by multi-dimension regression analysis that the electric activity of biceps and triceps muscles of the shoulder was correlated first of all with the work of load and then with loading force, muscle work and other mechanic and myographic characteristics. One could suppose that information on energy quantities was contained in afferentation signals of the nervous system to correct the program commands on the spinal level. The purpose of correction was to preserve constant quantity of energy expenditure, as well as accuracy and duration of movement. PMID- 1911928 TI - Toward gene therapy for Gaucher disease. AB - We are studying the transfer and expression by retroviral vectors of the human glucocerebrosidase (GC) gene into bone marrow cells as a model of gene therapy for genetic diseases of hematopoietic cells. A simple retroviral vector (G2) was developed that contains a normal human GC cDNA under the control of the Moloney murine leukemia virus long-terminal repeat (LTR) enhancer/promoter. Murine bone marrow was transduced with the G2 vector and maintained in long-term bone marrow culture (LTBMC). Expression of the human GC gene in the transduced murine LTBMC cells exceeded the level of endogenous murine GC mRNA. Murine bone marrow cells were also transduced with G2 and transplanted into irradiated syngeneic recipients. High levels of GC gene transfer and expression were seen in day-12 CFU-S foci, and to a lesser extent in the hematopoietic organs 4 months after gene transfer/bone marrow transplant (BMT). Human bone marrow, from a patient with Gaucher disease, was also used in studies of GC gene transduction. Gene transfer into 35-40% of the Gaucher hematopoietic progenitor cells was achieved, following prestimulation of the marrow with recombinant hematopoietic growth factors. Equal rates of gene transfer were obtained using either total marrow mononuclear cells or progenitor cells enriched 100-fold by immunomagnetic bead separation. GC gene transduction corrected the enzymatic deficiency of the Gaucher marrow. Our results demonstrate the potential utility of retroviral vector-mediated gene transfer for gene therapy of Gaucher disease. Current efforts are aimed at achieving more consistent in vivo GC expression in the murine BMT model and demonstrating transduction of pluripotent human hematopoietic stem cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1911930 TI - HIV infection and gene transfer therapy. PMID- 1911929 TI - Lymphocyte gene therapy. AB - Genetically corrected T cells are currently under investigation as a treatment for severe combined immunodeficiency disease resulting from a lack of adenosine deaminase (ADA). Monthly injections of these ADA-corrected T cells have resulted in measurable ADA activity in the peripheral blood and the in vivo production of antibody to blood group antigen. Genetically corrected T cells appear to be clinically valuable vehicles for gene therapy. PMID- 1911931 TI - Correction of murine mucopolysaccharidosis type VII (MPS VII) by bone marrow transplantation and gene transfer therapy. PMID- 1911933 TI - Petition to amend the National Institutes of Health Guidelines for Research Involving Recombinant DNA Molecules to establish a Public Policy Advisory Committee. Foundation on Economic Trends, September 18, 1990. PMID- 1911932 TI - Human gene therapy: ethics and public policy. AB - The first three human gene transfer/therapy clinical protocols are now underway after having been subjected to an extensive review process by the Recombinant DNA Advisory Committee (RAC) and its Human Gene Therapy Subcommittee. The "Points to Consider" document developed by the RAC established the framework for evaluating genetic intervention protocols. This review process is taking place in a broader social context. Public attitude surveys in this country have indicated a general lack of knowledge in the area of genetic engineering but an acceptance of somatic cell gene therapy as treatment for disease. Internationally, numerous policy statements on human genetic intervention have been published, all of which support the moral legitimacy of somatic-cell gene therapy for the cure of disease. The debate over the ethical issues related to somatic-cell gene therapy has evolved over a ten-year-period. The time has now come to begin a formal public process for the ethical assessment of germ-line genetic intervention. PMID- 1911934 TI - Autologous bone marrow transplant for children with AML in first complete remission: use of marker genes to investigate the biology of marrow reconstitution and the mechanism of relapse. PMID- 1911935 TI - Tandem duplications of the lac region of the Escherichia coli chromosome. AB - Tandem duplications are caused by unequal crossing over between homologous sequences. Duplications in the lac region of the Escherichia coli chromosome were isolated by two methods. Duplication frequency using a method involving P1 transduction increased from 0.4% with no UV to 2.0% following UV irradiation at 35 J/m2. Duplication frequency in lac using a second generalizable method that does not involve P1 transduction increased from 0.7 to 12% at 35 J/m2 UV. In both cases the duplication frequency began to plateau at UV doses of 12 J/m2 and 24 J/m2. According to segregation analysis of sixteen duplications there may be at least seven classes of duplications isolated by each method. Pulsed-field gel electrophoresis was used to measure the duplications isolated without P1 transduction. The minimum size of the duplications ranged from 30 to 320 kb but could be much larger. PMID- 1911936 TI - Conversion of large heterologies in Streptococcus pneumoniae. AB - In genetic transformation, long deletions dramatically increase the frequency of wild-type recombinants in 2-point crosses. In 3-point crosses in which the deletion was localized between 2 point mutations we demonstrated that this hyper recombination was the result of genetic conversion extending over several scores of bases outside the deletion. As this conversion did not require an active DNA polymerase A gene, it was proposed that the mechanism of conversion involves breakage and ligation between DNA molecules. A similar hyper-recombination was observed when donor DNA carried an insertion. These results suggest that long heterologies participated in recombination so that surrounding homologous regions are almost completely paired and that these long heterologies are converted. It appears that it is a process that evolved to correct errors of replication which lead to long deletions and which are not eliminated by other systems. PMID- 1911937 TI - Avoidance of inter-repeat recombination by sequence divergence and a mechanism of neutral evolution. AB - Eucaryotic genomes are loaded with diverse repeated sequences and are therefore threatened by rearrangements via inter-repeat crossovers and by gene-inactivating conversions between genes and their inactive pseudogenes. Such repeated DNA sequences are usually diverged and polymorphic. Sequence divergence by well spread point mutations is a potent inhibitor of homologous recombination due to the loss of recombination initiation sites and to the editing of recombinational intermediates by the mismatch repair system. Evidence is reviewed suggesting that a germ line process can identify duplicated sequences by homologous pairing, modify them by methylation and mutate by C----T transitions. Since this process requires a minimum contiguous homology that is larger than the average exon size, it is proposed that fragmentation by intron inserts protects the coding sequences from inactivation by homologous interactions with their pseudogene sequences. PMID- 1911938 TI - Production of triple-stranded recombination intermediates by RecA protein, in vitro. AB - During the directional strand exchange that is promoted by RecA protein between linear duplex DNA and circular single-stranded DNA, a triple-stranded DNA intermediate was formed and persisted even after the completion of strand transfer followed by deproteinization. In the deproteinized three-stranded DNA complexes, the sequestered linear third strand resisted digestion by E coli exonuclease I. In relation to polarity of strand exchange which defines the proximal and distal ends of the duplex DNA, when homology was restricted to the distal region of duplex substrate, the joints formed efficiently and were stable even upon complete deproteinization. Enzymatic probing of deproteinized distal joints with nuclease P1 revealed that the joints consist of long three-stranded structures that at neutral pH lack significant single-stranded character in any of the three strands. Instead of circular single-stranded DNA, when a linear single strand is recombined with partially homologous duplex DNA, in the presence of SSB, the formation of homologous joints by RecA protein, is significantly more efficient at distal end than at the proximal. Taken together, these observations suggest that with any single-stranded DNA (circular or linear), RecA protein efficiently promotes the formation of distal joints, from which, however, authentic strand exchange may not occur. Moreover, these joints might represent an intermediate which is trapped into a stable triple stranded state. PMID- 1911939 TI - The split-end model for homologous recombination at double-strand breaks and at Chi. AB - In recent years two different styles of model for homologous recombination have been discussed, depending on whether or not the recombination event occurs in the vicinity of a double-strand break in DNA. The models of Holliday and Meselson and Radding exemplify those that do not involve a break whereas the model of Szostak et al is taken as an example of those that do. Recent advances in understanding a prototypic recombination system thought to promote exchange distant from DNA ends, at Chi sites, suggest a mechanism of initiation neither like Holliday/Meselson-Radding nor like Szostak et al. In those models, only one strand of DNA may invade a homologous DNA molecule. We propose a model for Chi in which exonuclease degrades DNA from a double-strand break to the Chi site; the exonuclease is converted into a helicase upon interaction with Chi; unwinding produces a recombinagenic split-end, and both 3'- and 5'-ending strands at the split-end are capable of invading a homologue. Different genetic consequences are proposed to result from invasion by each. We review evidence supporting the split end model and suggest its application in at least some cases previously considered to proceed via the Meselson/Radding model and by the double-strand break repair model of Szostak et al. PMID- 1911940 TI - UV induction of LexA independent proteins which could be involved in SOS repair. AB - The SOS response is induced in E coli following treatments that interfere with DNA replication. The response is under the control of the recA and the lexA genes. Strains defective in LexA repressor constitutively express SOS proteins. However, SOS repair does not reach its maximum level in these strains. Instead, an activation of RecA protein and de novo protein synthesis are required for full repair. We have analyzed by 2-dimensional gel electrophoresis the induction of proteins after UV irradiation of lexA(Def) bacteria. Proteins which might participate in SOS repair are induced under these conditions. PMID- 1911941 TI - Mechanism of specific LexA cleavage: autodigestion and the role of RecA coprotease. AB - Specific LexA cleavage can occur under two different conditions: RecA-mediated cleavage requires an activated form of RecA, while an intramolecular self cleavage termed autodigestion proceeds spontaneously at high pH and does not involve RecA. The two cleavage reactions are closely related. We postulate that RecA stimulates autodigestion rather than acting as a typical protease, and it is proposed to term this activity 'RecA coprotease' to emphasize this indirect role. The mechanism of autodigestion is similar to that of a serine protease, and RecA appears to act by reducing the pKa of a critical lysine residue LexA. A new class of mutants, termed lexA (IndS), is described; these mutations increase the rate of LexA cleavage. PMID- 1911942 TI - DNA binding properties of the LexA repressor. AB - The LexA repressor from Escherichia coli negatively regulates the transcription of about 20 different genes upon binding with variable affinity to single-, double- or even triple-operators as in the case of the recN gene. Binding of LexA to multiple operators is cooperative if the spacing between these operators is favorable. LexA recognizes DNA via its amino-terminal domain. The three dimensional structure of this domain has been determined by NMR measurements. It contains three alpha-helices spanning residues 8-20, 28-35 and 41-54. In view of this structure, but also according to homology considerations and the unusual contact pattern with the DNA backbone, the LexA repressor is not a normal helix turn-helix DNA binding protein like for example phage lambda repressor. LexA is at best a distant relative of this class of transcription factors and should probably be considered as a protein that contains a new DNA binding motif. A cluster of LexA mutant repressors deficient in DNA binding falling into the third helix (residues 41-54 bp) suggests that this helix is involved in DNA recognition. PMID- 1911943 TI - SOS-inducible DNA polymerase II of E coli is homologous to replicative DNA polymerase of eukaryotes. AB - The polB gene of Escherichia coli encodes DNA polymerase II whose role in vivo is not defined. The polB gene has been cloned and shown to be identical to a DNA damage-inducible gene dinA which is regulated by the LexA repressor. Nucleotide sequencing of polB reveals that E coli DNA polymerase II is highly homologous to replicative DNA polymerases of eukaryotes which include human DNA polymerase alpha and Saccharomyces cerevisiae DNA polymerases I, II and III. The polB gene is not required for growth, UV-repair and UV-mutagenesis. PMID- 1911944 TI - Novel SOS phenotypes caused by second-site mutations in the recA430 gene of Escherichia coli. AB - E coli recA430 mutants are recombination-proficient, extremely UV sensitive, UV nonmutable and partially deficient in RecA-mediated proteolysis and in RecA dependent 'induced replisome reactivation' (IRR), the ability to recover DNA replication activity after UV irradiation. To determine how this pleiotropic phenotype can be altered by mutation, we isolated 10 independent derivatives of a recA430 strain, selecting for increased UV resistance. Eight of the 10 owed their resistance to altered recA alleles. We here describe the phenotypes conferred by two of the new recA alleles (recA720 and recA727), each of which contains the original recA430 mutation (G662 to A) and a second-site transition: T167 to C in recA720, and G103 to A in recA727. The second-site change in recA720 suppresses all the defects caused by recA430, and causes RecA720 to exhibit greater activity than RecA+ in some respects. Some, but not all, of the recA430 defects are partially corrected by the second-site mutation in recA727. PMID- 1911945 TI - Repression of the E coli recA gene requires at least two LexA protein monomers. AB - To analyze the DNA binding domain of E coli LexA repressor and to test whether the repressor binds as a dimer to DNA, negative dominant lexA mutations affecting the binding domain have been isolated. A large number of amino acid substitutions between amino acid positions 39 and 46 were introduced using cassette mutagenesis. Mutants defective in DNA binding were identified and then examined for dominance to lexA+. A number of substitutions weakened repressor function partially, whereas other substitutions led to a repressor with no demonstrable activity and a defective dominant phenotype. Since the LexA binding site has dyad symmetry, we infer that this dominance results from interaction of monomers of wild-type LexA protein with mutant monomers and that an oligomeric form of repressor binds to operator. The binding of LexA protein to operator DNA was investigated further using a mutant protein, LexA408, which recognizes a symmetrically altered operator mutant but not wild-type operator. A mixture of mutant LexA408 and LexA+ proteins, but neither individual protein, bound to a hybrid recA operator consisting of mutant and wild-type operator half sites. These results suggest that at least 1 LexA protein monomer interacts with each operator half site. We discuss the role of LexA oligomer formation in binding of LexA to operator DNA. PMID- 1911946 TI - The promoter of the recA gene of Escherichia coli. AB - The growth defect of a lambda phage carrying a recA-lacZ fusion was used to select mutations that reduced recA expression. Nine single base changes in the recA promoter were isolated that reduced both induced and basal (repressed) levels of expression. Deletion analysis of the promoter region and mapping of transcripts indicated that there is one main promoter responsible for both basal and induced expression. Some of the mutants displayed a lowered induction ratio, raising the possibility that there is a second, weak promoter that is not regulated by the SOS response. When one of the mutants was examined, it showed normal affinity for LexA repressor binding to the operator site. Binding of RNA polymerase to this mutant promoter, however, was much reduced. Further binding experiments suggested that LexA does not block RNA polymerase binding to the recA promoter, but inhibits a later step in initiation. PMID- 1911947 TI - Substitution of UmuD' for UmuD does not affect SOS mutagenesis. AB - In order to study the role of UmuDC proteins in SOS mutagenesis, we have constructed new Escherichia coli K-12 strains to avoid i) over-production of Umu proteins, ii) the formation of unwanted mixed plasmid and chromosomal Umu proteins upon complementation. We inserted a mini-kan transposon into the umuD gene carried on a plasmid. The insertion at codon 24 ends protein translation and has a polar effect on the expression of the downstream umuC gene. We transferred umuD24 mutation to the E coli chromosome. In parallel, we subcloned umuD+ umuC+ or umuD' umuC+ genes into pSC101, a low copy number plasmid. In a host with the chromosomal umuD24 mutation, plasmids umuD+ umuC+ or umuD' umuC+ produced elevated resistance to UV light and increased SOS mutagenesis related to a gene dosage of about 3. UV mutagenesis was as high in umuD' umuC+ hosts devoid of UmuD+ protein as in umuD+ umuC+ hosts. UmuD' protein, the maturated form of UmuD, can substitute for UmuD in SOS mutagenesis. PMID- 1911948 TI - A RecA protein mutant deficient in its interaction with the UmuDC complex. AB - recA1730 is a dominant point mutation preventing SOS mutagenesis. We demonstrate here that: i) RecA1730 fails to produce mutagenesis even though UmuD' is formed, ii) recA1730, when complemented by recA+, can cleave LexA protein and it displays a UmuDC- phenotype in spite of adequate concentrations of matured UmuD' and UmuC proteins, iii) the Mut- phenotype caused by RecA1730 is partially alleviated by MucAB proteins, functional analogs of UmuDC. To explain the mutant phenotype, we postulate that recA1730 impairs a RecA function required for the positioning of the UmuD'C complex within the replisome at the site of lesions. PMID- 1911949 TI - Mutagenic DNA repair in Escherichia coli. XIX. On the roles of RecA protein in ultraviolet light mutagenesis. AB - An experimental system was used in which His+ mutations induced by ultraviolet light (UV) arise from non-photo-reversible photoproducts whereas lethality is largely determined by photoreversible photoproducts. By exposing a strain with a deletion through recA to light immediately after UV, it was possible to examine mutagenesis under conditions where survival was not significantly different from 100%. No UV mutagenesis was seen in the absence of RecA protein even though the rest of the SOS system was fully expressed due to the presence of a defective LexA repressor and the active carboxy-terminal fragment of UmuD was present as a result of an engineered plasmid-borne gene. We conclude that RecA protein has a third essential function if UV mutagenesis is to be detected in excision deficient-bacteria. Another experiment showed that in exerting this function RecA protein does not need activation by pyrimidine dimers elsewhere on the genome, in contrast to its protein-cleavage mediation functions with LexA and UmuD proteins. RecA1730 protein blocked UV mutagenesis unless delayed photoreversal was given showing that the third function of RecA protein is not in the misincorporation step. It is therefore most likely to be in the bypass step where UmuD' and UmuC are postulated to act, although the possibility cannot be excluded that RecA protein is required for some other survival function distinct from translesion synthesis. PMID- 1911950 TI - Roles of recA mutant allele (recA495) in frameshift mutagenesis. AB - The chemical carcinogen N-acetoxy-N-2-acetylaminofluorene (N-AcO-AAF) induces frameshift mutations located within two types of specific sequences (mutation hot spots): i) contiguous guanine sequences and ii) alternating GC sequences. The genetic requirements of these frameshift events were investigated using specific reversion assays. AAF-induced -2 frameshift mutagenesis at alternating GC sequences is peculiar in that it requires a LexA- controlled function which is not UmuDC and occurs in the absence of RecA protein, provided the SOS regulon is derepressed. Moreover, the non-activated form of the RecA protein was shown to act as an inhibitor in this mutation pathway. As we were interested in elucidating this mutation pathway, we have developed a convenient spot reversion assay specific for the detection of this class of mutations. This assay allowed us to isolate E coli mutants affected either in repair or mutagenesis functions. One particular mutant, recA495, is very sensitive to UV and N-AcO-AAF, and is defective in recombination and UV mutagenesis. The RecA495 protein exhibits very low binding to both single- and double-stranded DNA. We show that when the SOS regulon is derepressed, the recA495 allele has two contrasting roles in frameshift mutagenesis: i) it prevents the induction of -1 frameshift mutations at repetitive sequences and ii) it is permissive for the induction of -2 frameshift mutations within alternating GC sequences. PMID- 1911951 TI - Properties of the Escherichia coli RuvA and RuvB proteins involved in DNA repair, recombination and mutagenesis. AB - The ruvA and ruvB genes constitute an operon, which is regulated by the SOS system and involved in DNA repair, recombination and mutagenesis. RuvA protein binds to both single-stranded and double-stranded DNA. RuvB protein has weak ATPase activity. RuvA bound to DNA greatly enhances ATPase activity of RuvB. UV irradiation to supercoiled DNA further enhances the stimulatory effect of RuvA on the RuvB ATPase activity. In the presence of ATP the RuvA-RuvB complex has an activity that renatures cruciform structures formed by heating and gradually cooling supercoiled DNA with an inverted repeat. These findings suggest that the RuvA-RuvB complex interacts with an irregular conformation in damaged DNA and induces conformational changes in DNA using energy provided by ATP hydrolysis, so that it facilitates DNA repair, recombination and error prone replication. PMID- 1911952 TI - A possible interaction of single-strand binding protein and RecA protein during post-ultraviolet DNA synthesis. AB - The mechanism of DNA replication in ultraviolet (UV)-irradiated Escherichia coli is proposed. Immediately after UV exposure, the replisome aided by single-strand DNA-binding protein (SSB) can proceed past UV-induced pyrimidine dimers without insertion of nucleotides. Polymerisation eventually resumes somewhere downstream of the dimer sites. Due to the limited supply of SSB, only a few dimers can be bypassed in this way. Nevertheless, this early DNA synthesis is of great biological importance because it generates single-stranded DNA regions. Single stranded DNA can bind and activate RecA protein, thus leading to induction of the SOS response. During the SOS response, the cellular level of RecA protein increases dramatically. Due to the simultaneous increase in the concentration of ATP, RecA protein achieves the high-affinity state for single-stranded DNA. Therefore it is able to displace DNA-bound SSB. The cycling of SSB on and off DNA enables the replisome to bypass a large number of dimers at late post-UV times. During this late replication, the stoichiometric amounts of RecA protein needed for recombination are involved in the process of postreplication repair. PMID- 1911953 TI - rec genes and homologous recombination proteins in Escherichia coli. AB - The twenty-five years since the first published report of recA mutants in Escherichia coli has seen the identification of more than 12 other recombination genes. The genes are usually grouped into three pathways named RecBCD, RecE and RecF for prominent genes which function in each. A proposal is made here that there are two RecF pathways, one sensitive and one resistant to exonuclease I, the SbcB enzyme. Five methods of grouping the genes functionally are discussed: 1) by enzyme activity, 2) by common indirect suppressor, 3) by common phenotype, 4) by common regulation and 5) by epistasis. Five classes of enzyme activities implicated in recombination are discussed according to their involvement in presynapsis, synapsis or postsynapsis: 1) nucleases 2) helicases 3) DNA-binding proteins 4) topoisomerases and 5) ligases. Plausible presynaptic steps for the RecBCD, RecF (SbcBS) and RecE pathways show the common feature of generating 3' terminated single-stranded DNA (ssDNA). On this ssDNA it is proposed that a RecA protein filament is generated discontinuously. This implies the existence of nucleation and possibly measurement and 3' end protection proteins. Specific proposals are made for which recombination genes might encode such products. Finally the generality of the RecA-ssDNA-filament mechanism of synapsis in the cellular biological world is discussed. PMID- 1911954 TI - Recurrent vulvovaginal candidosis. PMID- 1911955 TI - Official estimates and AIDS epidemiology. PMID- 1911956 TI - Risk of HIV infection among Dutch expatriates in sub-Saharan Africa. AB - In order to study the prevalence of human immunodeficiency virus (HIV) infections and related risk factors, Dutch expatriates returning from sub-Saharan Africa were asked to complete a questionnaire on sexual, occupational and other risk factors, and to donate a sample of blood to test for antibodies against HIV. The 1968 participants were workers of various professions and their family members over 16 years of age posted in sub-Saharan African countries by Dutch governmental, non-governmental and commercial organizations for at least 6 months cumulative time between 1 January 1979 and 1 January 1990. Antibodies against HIV 1 were found among 4 of 1122 men (0.4%) and 1 of 846 women (0.1%). The woman and 3 of the men had had sexual contact with African partners and had been treated for sexually transmitted diseases, 2 of these 3 men also had an African life partner. One man reported occupational exposure only. Of the 1968 participants 89 men (7.9%) and 18 women (2.1%) lived with an African partner; 344 men (30.7%) and 111 women (13.1%) had heterosexual contact with other African partners. Only 22.3% (men) and 18.6% (women) of casual sexual contacts with African partners were always protected by a condom. Two hundred and thirty-two of 408 (56.9%) (para)medics reported needlesticks. Groups at risk of HIV infection through sexual exposure were identified using logistic regression models. In conclusion, the observed prevalence of HIV-1 is low. However, unprotected sexual contact with African partners and needlestick accidents were common. This study underscores the continuous need for health education of expatriates on the risks of transmission of HIV in Africa. PMID- 1911957 TI - Sexual assault on men. AB - Epidemiological data in 13 cases of sexual assault on men who attended a sexual assault referral centre are presented. All the assailants were male. The sexual orientation of the victims was predominantly heterosexual (7 of 13), 3 considered themselves to be homosexual and 3 were confused about their sexual orientation. The average age at the time of assault was 21.6 years. The most common form of assault was anal intercourse which occurred in 8 cases, followed by forced oral penetration which occurred in 6 cases. The proportion of known:unknown assailants (8:5) shows similar characteristics to those seen in female rape, use of weapons and multiple assailants were more common in assault on men. Seven men (54%) developed psychological problems following assault, and this was their main reason for presentation to the centre. PMID- 1911958 TI - Detection of Mycoplasma genitalium in the genitourinary tract of women by the polymerase chain reaction. AB - A polymerase chain reaction (PCR) was used to demonstrate the presence or absence of Mycoplasma genitalium in the lower genital tract of 57 women who attended a sexually transmitted diseases clinic. The mycoplasma was detected in the cervix of 10 (17.5%) women and also in the vagina of 4 (16%) and the urethra of 6 (24%) of 25 women from whom multiple samples were obtained. Chlamydia trachomatis was detected also by a PCR in 9 (16%) of the women, but only 3 were chlamydia positive and mycoplasma-positive. M. genitalium was detected occasionally in women with vaginal disease (for example, bacterial vaginosis), whereas C. trachomatis was not, but whether there is any causal relationship between the mycoplasma and vaginal or cervical disease requires further study. PMID- 1911959 TI - AIDS-related risk perception and sexual behaviour among sexually transmitted disease clinic attenders. AB - Perception of risk has been suggested as an important element of sexual behaviour change among people who engage in behaviours which place them at risk of HIV infection. A study of the relationship between perception of risk of HIV infection and risk-related sexual behaviours was conducted in a genitourinary medicine clinic. The sample comprised 767 patients attending over a 3-month period; data collection was by self-completed questionnaire. A total of 574 questionnaires were suitable for analysis, representing a response rate of 75%. The majority of people in the sample reported behaviours which increased their risk of HIV infection, but only 19% (n = 112) of the sample perceived themselves to be personally 'at risk', despite adequate knowledge of HIV transmission and methods of risk reduction. Significant differences between social class groups were found for knowledge scores, with highest scores among professionals and lowest among unemployed subjects (Kruskal Wallis test chi 2 = 24.6, P less than or equal to 0.001). Increasing age was significantly associated with better knowledge; significantly more young people aged 16-20 years who did not perceive themselves 'at risk' (64%), had lower knowledge scores than older people who did not perceive themselves 'at risk' (41%). Among heterosexuals who reported having sex with other people in addition to their regular partner, 79% did not perceive themselves as 'at risk' of HIV infection, and of these, 64% reported only infrequent condom use with casual sexual partners. Significantly more heterosexual men (67%) than women (44%) reported multiple sex partners.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1911960 TI - Diagnosing non-gonococcal urethritis: the gram-stained urethral smear in perspective. AB - The value of microscopy of a Gram-stained urethral smear in the diagnosis of non gonococcal urethritis and chlamydial urethral infection was assessed in 153 men attending a department of genitourinary medicine. A mean of more than 4 polymorphs in 5 fields (x1000) was considered to be abnormal. In the diagnosis of urethritis, the sensitivity (94%), specificity (91%), positive predictive value (93%) and negative predictive value (93%) were high. In the diagnosis of chlamydial infection, sensitivity (91%) and negative predictive value (96%) were high, but specificity (68%) and positive predictive value (46%) were low. In men with symptoms of genitourinary infection, the sensitivity (96.7%) and negative predictive value (97.4%) of the Gram-stained urethral smear in the diagnosis of chlamydial infection was comparable with modern chlamydial antigen detection tests. PMID- 1911961 TI - Primary and secondary syphilis: a histopathological study. AB - We present a study of biopsies taken from skin lesions of 44 patients presenting with primary or secondary syphilis. In most primary lesions erosion or, more often, ulceration was present, with a dense inflammatory infiltrate. In secondary syphilis a wide variety of histological changes was present. Blood vessels were frequently involved, with marked endothelial swelling and often proliferation. Treponemes were demonstrated with the Steiner staining method in all investigated cases of primary syphilis and in 71% of secondary syphilis cases. Treponemes were present throughout the dermis, particularly perivascularly, and in the dermal epidermal junction zone. In two specimens of secondary syphilis treponemes were located predominantly in the epidermis, but there were always some microorganisms demonstrable in the dermis. The inflammatory infiltrate was often located in a perivascular coat-sleeve-like arrangement. In this study plasma cells and lymphocytes were present in all specimens of primary and secondary syphilis. Syphilitic lesions differed from yaws lesions mostly in the location of treponemes and the affection of blood vessels. In this histopathological study of early syphilis, treponemes did not show the epidermiotropic character of yaws, and blood vessel changes were more pronounced than in yaws. Unfortunately, due to the protean histopathological manifestations described in venereal syphilis and in yaws, these two treponemal diseases cannot always be differentiated on histological grounds alone. PMID- 1911962 TI - Does first episode genital herpes have an incubation period? A clinical study. AB - A restrospective survey of the notes of 146 patients with culture-positive first episode genital herpes simplex infection produced 37 men and 37 women in whom the incubation period could be established from their own and their partners' notes. In 9 patients the period was 1-12 days, in 20 men it ranged from 1 to 49 days and in 11 women from 1 to 28 days. In 7 patients it was much longer. In 28 patients a first episode of genital herpes developed during an ongoing monogamous relationship. These findings indicate that the incubation period of genital herpes may be longer than hitherto recognized and have implications for counselling and control. PMID- 1911963 TI - Transmission of HIV in a family during 10 symptomless years. PMID- 1911964 TI - Listeriosis in AIDS: consequence and cofactor? PMID- 1911965 TI - Seminoma and HIV infections. PMID- 1911966 TI - Ecthyma gangrenosum without bacteraemia in an HIV seropositive male. PMID- 1911967 TI - Knowledge and impact of AIDS in Gabon. PMID- 1911968 TI - Neurosyphilis and HIV. PMID- 1911969 TI - AIDS Literature Index. PMID- 1911970 TI - Picture archiving and communication systems and related developments in Sweden. AB - Large PACS (Picture Archiving and Communication Systems) installations do not yet exist in Sweden, but some hospitals have had experience with limited PACS activities. At present there are four mini PACS installations in radiology departments and about 12 teleradiology systems in use in Sweden. A couple of small Swedish enterprises work in the market segment of digital imaging including PACS and teleradiology, although the radiology market is dominated by the large international companies. Interest in PACS and teleradiology in Sweden has increased during the last few years, along with advancements in technology and international experience. However, radiology is organized very differently in the United States, Japan, Southern Europe, and Scandinavia. Because of this, PACS will be introduced in different ways, and experience with PACS gained in one health care system may differ from that gained from other health care systems. This article reviews the status of PACS and related developments in Sweden. PMID- 1911971 TI - Three-dimensional imaging of the lung in vivo: work in progress. AB - It has previously been demonstrated that three-dimensional (3D) displays of the lung and bronchial tree can be generated from computed tomography (CT) scans of lung specimens. Subsequent refinement of the reconstruction algorithms has allowed high-resolution reconstructions of lungs in vivo. With the introduction of low-dose CT scan protocols, use of the technique may become more common in the radiologic community. The many potential clinical applications for 3D imaging of the lung include an aid to bronchoscopy and improved surgical planning. We present the technical details for 3D imaging of the lungs in vivo as well as three representative case studies. PMID- 1911972 TI - Calcaneal and pelvic fractures: diagnostic evaluation by three-dimensional computed tomography scans. AB - A major application of three-dimensional (3D) computed tomography (CT) is in the imaging of the skeleton. 3D CT has a potentially important role in determining the presence, type, and extent of fractures, especially of the calcaneus and pelvis. The objective of this study was to compare the diagnostic sensitivity and specificity of 3D CT, CT slices, and plain radiography in the detection and characterization of calcaneal and pelvic fractures. 3D CT reconstructions were obtained by two methods, surface reconstruction and volumetric techniques. Twenty eight patients were imaged with CT, 3D CT, and plain radiography. The opinion of a musculoskeletal radiologist with access to all images plus clinical history, surgical findings, and follow-up findings was taken as truth. Four additional musculoskeletal radiologists read these cases in a blinded fashion and ranked the modalities with regard to perceived utility. Receiver operating characteristic analysis was used to determine the relative value of each modality in terms of diagnostic quality. All imaging modalities performed comparably in the diagnosis of fractures. CT slices and plain-films were the most useful for more difficult diagnostic tasks such as fracture stability, and the presence of comminution and estimation of the number of fragments. The results suggest that for skeletal areas with complicated anatomy (such as the pelvis and calcaneus), the diagnostic value of 3D CT is often equivalent to that of conventional methods. PMID- 1911973 TI - Evaluation of congenital heart disease by three-dimensional magnetic resonance imaging. AB - This study was undertaken to compare electrocardiographically gated magnetic resonance imaging (MRI) to established imaging modalities in the detection of complex intra- and extracardiac morphologic defects. Twenty-three patients with congenital cardiac abnormalities were imaged by four methods: cardiac catheterization, echocardiography, two-dimensional (2D) transaxial MRI, and three dimensional (3D) MRI surface reconstruction. Observers with experience in congenital cardiac disease diagnosis (two for echo, one for catheterization, two for 2D MR, and three for 3D MR) evaluated the images in a blinded fashion, and the results were analyzed with receiver operating characteristic (ROC) analysis. Overall, cardiac catheterization had the best diagnostic performance. The diagnostic value of routine 2D cardiac MR images and 3D MR reconstruction images were similar to that of echocardiography. All of the modalities performed poorly in the diagnosis of extracardiac defects and atrial septal defects. PMID- 1911974 TI - Surface and volume rendering in three-dimensional imaging: a comparison. AB - Many surface rendering techniques are currently available for the three dimensional display of structure data captured by imaging devices. Comparatively fewer volume rendering techniques are also available for the same purpose. The relative performance of these two methodologies in visualization tasks has been a subject of much discussion recently. Although it is very desirable to establish, based on observer studies, objective guidelines stating the relative merits of the two methodologies even for specific situations, it is impossible to conduct meaningful observer studies that take into account the numerousness of the techniques in each methodology, and within each technique, the numerousness of the parameters and their values that control the outcome of the technique. Our aim in this article is to compare the two methodologies purely on a technical basis in an attempt to understand their common weaknesses and disparate strengths. The purpose of this article is twofold--to report a new surface rendering technique and to compare it with two volume rendering techniques reported recently in the literature. The bases of comparison are: ability to portray thin bones; clarity of portrayal of sutures, fractures, fine textures, and gyrations; smoothness of natural ridges and silhouettes; and computational time and storage requirements. We analyze the underlying algorithms to study how they behave under each of these comparative criteria. Our conclusion is that, at the current state of development, the surface method has a slight edge over the volume methods for portrayal of information of the type described above and a significant advantage considering time and storage requirements, for implementations in identical environments. PMID- 1911976 TI - Digital imaging in the radiation oncology environment: a personal computer local area network solution. AB - Personal computer (PC) driven digital imaging devices are now becoming available in the market place for use in radiation oncology to produce what are known as real time portal images. These limited contrast images are used to verify the patient anatomy under treatment by megavoltage x-rays and are a vital part of the patient treatment. The current generation of devices can produce both single and movie loop images in real time for physician review and approval. To disseminate these images and other digital images used in the planning and delivery of radiation therapy, a PC-based picture archiving and communications system has been developed that is tailored to the special needs of radiation oncology. PMID- 1911975 TI - Realistic viewing and manipulation of radiographic images on a personal computer- a user interface for educational applications. AB - The authors have designed a user interface for the display and manipulation of radiographic images that is intended for use in digitized teaching files and computer-aided instruction (CAI) applications. By making the way the viewer interacts with a set of digitized images on the computer screen as similar as possible to the interaction with conventional films on a view-box the authors have tried to create a system that combines the directness of the conventional teaching file with the power and flexibility of CAI. This is accomplished on readily available personal computer workstations. PMID- 1911977 TI - Data base management in radiology: a simplified approach. AB - The increasing availability of personal and departmental computers in radiology departments has led to increasing interest in data management. Data base management software must be system compatible, simple, and flexible to insure its acceptance and constant use. Once in place, such a system streamlines the daily documentation of interesting cases for conference, follow-up, research, and quality assurance. The authors have developed such a data base program for tracking computed body tomography cases in their department, which can be run as a portable computer to maximize ease of access and therefore usage. PMID- 1911978 TI - Image data compression using a new floating-point digital signal processor. AB - A new dual-ported, floating-point, digital signal processor has been evaluated for compressing 512 and 1,024 digital radiographic images using a full-frame, two dimensional, discrete cosine transform (2D-DCT). The floating point digital signal processor operates at 49.5 million floating point instructions per second (MFLOPS). The level of compression can be changed by varying four parameters in the lossy compression algorithm. Throughput times were measured for both 2D-DCT compression and decompression. For a 1,024 x 1,024 x 10-bit image with a compression ratio of 316:1, the throughput was 75.73 seconds (compression plus decompression throughput). For a digital fluorography 1,024 x 1,024 x 8-bit image and a compression ratio of 26:1, the total throughput time was 63.23 seconds. For a computed tomography image of 512 x 512 x 12 bits and a compression ratio of 10:1 the throughput time was 19.65 seconds. PMID- 1911979 TI - Analysis of prostaglandins in aqueous solutions by supercritical fluid extraction and chromatography. AB - Trace amounts of prostaglandins (PGs) were selectively analysed without derivatization using supercritical fluid extraction (SFE) and open tubular column supercritical fluid chromatography (SFC). The specific compounds studied were prostaglandin F2 alpha (PGF2 alpha), esters of PGF2 alpha, prostaglandin F1 alpha) and prostaglandin E2 (PGE2). An open tubular column was used with carbon dioxide as the mobile phase and with universal flame ionization detection. Samples were introduced into the column by direct injection using a 1-microliter sample loop or by SFE with solute focusing. The 11 standard compounds were effectively separated within 35 min using a density program at constant temperature. The minimum detectable quantity (signal-to-noise ratio = 3) using the direct injection method was 9 ng for 15-propionate PGF2 alpha isopropyl ester. Using the extraction method, the sample size in the extraction cell was increased to 100 microliters, which made it possible to analyse compounds that were present in low concentrations. Aqueous PG samples were extracted from adsorbents onto which the samples had been loaded. PMID- 1911980 TI - Spectrophotometric determination of cimetidine in the presence of its acid induced degradation products. AB - Cimetidine has been determined in the presence of its acid-induced degradation products using a second derivative (D2-) spectrophotometric method (method I) or a colorimetric method (method II). The former is based on D2-value measurement at 216 nm, whilst the latter depends on charge-transfer complexation with dichlorophenol-indophenol. The two methods are proved to be stability indicating, since plots of log C% versus time were linear. The application to cimetidine determination in tablets and ampoules gave good results. PMID- 1911981 TI - Spectrophotometric methods for the determination of sulphathiourea. AB - Three simple and sensitive spectrophotometric methods are described for the determination of sulphathiourea. The methods are based on the interaction of this thioamide with either iodine, tetracyanoethylene (TCNE) or copper nitrate to give the corresponding charge-transfer or metal-ion complexes, which can be measured at 363, 350 and 353 nm, respectively. In each case, a 1:1 complex was formed. Beer's law is obeyed for each procedure in a concentration range of 1-150 micrograms ml-1. The proposed procedures can be applied to the determination of sulphathiourea in its pharmaceutical formulations. PMID- 1911982 TI - Rapid verification of identity and content of drug formulations using mid infrared spectroscopy. AB - A general method for the rapid verification of both identity and content of complete solid drug formulations has been devised. Infrared spectra for the samples were recorded using the diffuse reflectance technique, and specially written software was employed to identify the type of formulation and level of active ingredient. This software was devised to ensure reliable use when applied by those with minimal operator skills. Three differing drug tablet formulations containing simvastatin, enalapril maleate and lovastatin, as well as a capsule formulation containing finastride were studied. Adequate precision was obtained to reliably verify drug dosage levels. Near-infrared (NIR) and mid-infrared (MIR) spectrometers were evaluated for use with the method. The MIR instrument allowed sufficient resolution and spectral/structural selectivity to reliably verify correctness of either of two near derivative drugs necessarily present in the same clinical study. Drug tablet and capsule dosage levels tested ranged from 0.2 to 40 mg of drug. Approximately 1% (w/w) of the drug in the formulation was the minimum amount determined. Parameters affecting method ruggedness in routine use were optimized. Experimental addition of an extraneous material to a simvastatin formulation was easily detected and flagged by the routine test procedure. Subsequent data retrieval and searching against spectral libraries was used to demonstrate identification of the additive. PMID- 1911983 TI - Determination of mevalonolactone in capsules by capillary gas-liquid chromatography. AB - A wide bore capillary gas chromatographic method was developed to determine mevalonolactone in capsule formulations. The method uses beta,beta-dimethyl-gamma hydroxymethyl-gamma- butyrolactone as an internal standard and has been validated for its accuracy, precision and linearity. The method has been applied for stability testing of the capsule formulation. High-performance liquid chromatographic and gas chromatographic studies demonstrated cyclization of mevalonic acid (open-chain form) to mevalonolactone (cyclic form) under the described gas chromatography conditions. Mass spectrometric analysis indicated that mevalonolactone prepared in water or an organic solvent emerged from the gas chromatographic column as the intact cyclic lactone. PMID- 1911984 TI - Study of bioequivalence of magnesium and sodium valproates. AB - The in vivo bioavailability of magnesium valproate (500 and 1000 mg) enteric coated tablets has been compared with that of sodium valproate (Depakine) (500 and 1000 mg) enteric-coated tablets. The two preparations were found to be bioequivalent; magnesium valproate appeared to be a drug without bioavailability problems and with reduced inter-subject variability, compared with that of sodium valproate. A reversed-phase HPLC method for the determination of valproates is described. PMID- 1911985 TI - Optimization of selectivity in micellar chromatographic procedures for the determination of drugs in urine by direct injection. AB - Selectivity was optimized for the determination of drugs in urine by direct injection micellar chromatography through changes in specific mobile phase parameters. The role of mobile phase pH and the type of surfactant used for mobile phase preparation was investigated. The retention of the urine matrix was found to be minimal between pH 5.5 and 7.5. The non-ionic surfactant, polyoxyethylene 23 lauryl ether (Brij 35), was found to be the surfactant of choice for the separation of drugs from urine. Favourable retention of both the urine background and the analyte was achieved with this surfactant. Micellar mobile phases of optimal composition were used to develop chromatographic procedures for the determination of furosemide, hydrochlorothiazide and propranolol in urine. Good accuracy (98-102% of drug recovered), precision (1-4% RSD) and linearity were obtained for all methods. Limits of detection for all drugs were adequate. PMID- 1911986 TI - High performance liquid chromatographic analysis of a multicomponent product using a silica stationary phase and an aqueous-organic mobile phase. PMID- 1911987 TI - Determination of dextromethorphan and dextrorphan in urine by high-performance liquid chromatography after solid-phase extraction. PMID- 1911988 TI - Liquid chromatographic analysis of the adenosine agonist PD 117519 in dog plasma. PMID- 1911989 TI - Molecular diagnosis of alcelaphine herpesvirus (malignant catarrhal fever) infections by nested amplification of viral DNA in bovine blood buffy coat specimens. AB - A fragment of alcelaphine herpesvirus-1 (AHV-1; malignant catarrhal fever) DNA was subcloned into pUC 18 and sequenced. The subclone hybridized strongly to AHV 1 DNA, weakly to alcelaphine herpesvirus-2 (AHV-2) DNA, and not at all to DNA from bovine herpesvirus-1 (BHV-1; infectious bovine rhinotracheitis [IBR] virus), bovine herpesvirus-2 (BHV-2; bovine herpes mamillitis [BHM] virus), and bovine herpesvirus-4 (BHV-4; isolate DN599). A 2-stage (nested) polymerase chain reaction (PCR) diagnostic test was devised based on a portion of the subcloned AHV-1 DNA sequence. First and second stage amplified AHV-1 DNA targets were 487 and 172 base pairs (bp) in length, respectively. Unique Pvu II and Stu I restriction endonuclease cleavage sites confirmed the identity of amplified AHV-1 DNA. Five AHV-1 and 2 AHV-2 isolates were identically and specifically PCR positive. BHV-1, BHV-2, and BHV-4 viruses were negative by the same procedure. As little as 0.01 TCID50 AHV-1 was detected using the nested amplification procedure. Simple methods of buffy coat isolation from bovine blood were employed to prepare specimens for PCR. An AHV-1-infected calf was PCR positive from 3 to 77 days postinoculation (PI), with rising seroconversion first noted 14 days PI. The AHV-1 DNA sequence was 62% homologous to a portion of the Epstein-Barr virus genome. The nested PCR procedure may improve the viral diagnosis of clinical and subclinical alcelaphine herpesvirus infections. PMID- 1911990 TI - Identification of Treponema hyodysenteriae and Treponema innocens using two four hour identification systems. AB - Two 4-hour identification systems, the RapID-ANAII (Innovative Diagnostic Systems) and the ANI card (Vitek Systems), were used to identify isolates of Treponema hyodysenteriae and T. innocens. Twenty-one isolates of T. innocens and 53 isolates of T. hyodysenteriae were tested with both systems. With the ANI system, alpha-galactosidase was the only test that differentiated the two species. With the RapID-ANAII system, alpha-galactosidase and indole tests allowed differentiation of the two species. Treponema hyodysenteriae was alpha galactosidase negative and indole positive, whereas T. innocens produces the opposite reactions. Three isolates were alpha-galactosidase negative and indole negative. These isolates represent a group intermediate between the two officially described species. The two species of swine Treponema can be identified by commercial identification kits and a third group of isolates intermediate between the two species was identified. PMID- 1911991 TI - Suitability of the broth-disk elution test for evaluating susceptibility of obligate anaerobes to trimethoprim-sulfonamides. AB - Species of anaerobic bacteria isolated from clinical veterinary specimens were tested for susceptibility to trimethoprim-sulfonamides by the broth-disk elution technique. Three different media were used for each organism: prereduced anaerobically sterilized (PRAS) brain-heart infusion broth (BHI), thioglycollate broth, and a semidefined PRAS medium. Susceptibility results from these media were compared with those determined by interpreting the minimal inhibitory concentration obtained using an agar dilution technique. Results from broth-disk testing in semidefined medium agreed in 68.7% of the cases, in 53.7% for thioglycollate broth, and in 36.9% for BHI. The greatest deviation between techniques occurred with isolates belonging to the genus Bacteroides, followed by those of the genus Clostridium and those of the genus Fusobacterium. This deviation was directly proportional to increasing concentrations of thymidine in the BHI and thioglycollate broths but not with the semidefined medium. We conclude that the broth-disk elution method for measuring susceptibility of obligate anaerobes to trimethoprim-sulfonamides is unsuitable. PMID- 1911992 TI - Use of a Salmonella typhimurium-derived virulence probe in the detection of Salmonella sp. and in the characterization of S. cholerae-suis virulence plasmids. AB - A genetic probe encoding a virulence gene from Salmonella typhimurium was useful in the detection of Salmonella from feces during an outbreak of salmonellosis at a local dairy. A 3.2-kb BamHI restriction endonuclease fragment of the S. typhimurium virulence plasmid, pStSR100, has been useful as a DNA probe for both detection of Salmonella sp. and characterization of virulence plasmids from numerous field isolates. This virA probe hybridizes to a highly conserved gene carried on the large virulence plasmids of invasive Salmonella isolates. Colony blots prepared from feces directly plated onto MaConkey's agar failed to detect low numbers of Salmonella sp. However, hybridization of the VirA probe to vacuum blots or colony blots prepared from feces in tetrathionate enrichment broth incubated for 16 hours at 37 C was effective for detecting Salmonella sp. and resulted in an 85.9% correlation with culture results. The probe also demonstrated the highly conserved nature (96%) of the virulence gene among S. cholerae-suis isolate plasmids detected using Southern blot analysis. PMID- 1911993 TI - An outbreak of equine neonatal salmonellosis. AB - An outbreak of salmonellosis in foals occurred on a large Thoroughbred farm in California. Only foals less than 8 days of age exhibited clinical signs, which included depression, anorexia, and diarrhea. Three foals died from septicemia. The agent responsible was Salmonella ohio, which is rarely involved in salmonellosis in horses. During the course of the outbreak, S. ohio was isolated from 27 of 97 mares (27.8%) and 34 of 97 foals (35.1%). Mares were the presumed source of infection for foals. The absence of clinical signs in mares allowed for increased exposure of foals through environmental contamination. Although foals continued to become infected after strict control measures were adopted, none became ill. Salmonella serotypes of seemingly low virulence can produce serious disease outbreaks. PMID- 1911994 TI - Immunocytochemical detection of Ehrlichia platys antigens in canine blood platelets. AB - An avidin-biotin immunoperoxidase complex (ABC) immunocytochemical (ICC) stain procedure was optimized for detection of Ehrlichia platys antigens. Positive immunoreactivity was detected with dilutions of canine immune serum on acetone fixed smears of platelet-rich plasma from E. platys-infected dogs. No E. platys antigens were detected when this ICC stain was applied to frozen or paraffin embedded formalin- or acetone-fixed tissue sections from dogs with acute E. platys infection. Acetone fixation and freezing preserved ICC staining of ehrlichial antigens in infected blood platelets, whereas formalin treatment of similarly preserved E. platys-infected platelets nullified positive immunoreactivity. Significant E. platys infection of cells and tissues other than platelets may not occur. PMID- 1911995 TI - Toleration of high concentrations of dietary zinc by mink. AB - Adult and kit male and female natural dark ranch mink (Mustela vison) were fed a conventional diet supplemented with 0, 500, 1,000, or 1,500 ppm zinc, as ZnSO4.7H2O, for 144 days. No marked adverse effects were observed in feed consumption, body weight gains, hematologic parameters, fur quality, or survival. Zinc concentrations in liver, kidney, and pancreas of the mink increased in direct proportion to the zinc content of the diet. Histopathologic examination of the livers, kidneys, and pancreata revealed no lesions indicative of zinc toxicosis. The results indicate that mink can tolerate at least 1,500 ppm dietary zinc, as ZnSO4.7H2O, for several months without apparent adverse effects. PMID- 1911996 TI - Fumonisin B1 concentrations in feeds from 45 confirmed equine leukoencephalomalacia cases. AB - During the fall of 1989 and winter of 1990, numerous reports of equine leukoencephalomalacia (ELEM) occurred from many regions of the United States. Typically, horses were consuming feed partially or entirely composed of corn and/or corn screenings. From October 1989 through May 1990, samples from 55 confirmed or suspected ELEM cases were received at the National Veterinary Services Laboratories, Ames, Iowa, for fumonisin B1 analysis. Samples from 9 cases in 1984-1985 were also obtained. Fumonisin B1, a mycotoxin produced by Fusarium moniliforme, causes ELEM, but little is known of naturally occurring toxic or safe levels in feeds. To determine what levels of fumonisin B1 in feeds are associated with ELEM, 45 selected cases were studied. The fumonisin B1 concentrations ranged from less than 1 ppm to 126 ppm, with the majority of the samples above 10 ppm. All types of feeds were included: corn, screenings, sweet feeds, and commercially pelleted rations. The length of exposure varied from 7 to greater than 35 days. Horse feed samples not associated with ELEM were also collected and analyzed. None of the nonproblem feed samples contained fumonisin B1 levels greater than 8 ppm. PMID- 1911997 TI - An immunofluorescence test to determine the occurrence of type II collagen in muscle biopsies from cattle with rectovaginal constriction. AB - Type II collagen occurs in the muscles of rectovaginal constriction (RVC) affected and carrier cattle but not in normal cattle. Muscle biopsies from known RVC affected and carrier cattle and normal cattle were examined for the presence of Type II collagen using affinity purified goat anti-collagen II serum in a fluorescent antibody test. Type II collagen was consistently found in RVC affected animals (22 of 23 samples score positive). Rectovaginal constriction carrier animals had variable staining for the Type II collagen (25 of 47 samples scored positive). Some positive staining was also observed in the control animals (8 of 34 samples scored positive). Because of the variable occurrence of Type II collagen, the value of fluorescent antibody staining to identify RVC carrier animals is uncertain. PMID- 1911998 TI - Identification of immunoglobulin light chains in canine extramedullary plasmacytomas by thioflavine T and immunohistochemistry. AB - Extramedullary plasmacytomas were studied in 29 dogs. The site at which tumors occurred and the age and sex of the dogs were similar to those in previous reports. The skin of the digits, chin, ear, and lip represented the most common (17/29) tumor sites. Males and females were equally represented, and tumors occurred in middle-aged to old dogs (mean age, 9.0 years). A breed predilection was seen in the Cocker Spaniel (n = 7; 24%); Cocker Spaniels represented only 4% (210/4,725) of the submissions during the same period. Tumors were stained with immunohistochemical markers (lambda light chain, K light chain) and thioflavine T. Immunoreactivity was limited to either lambda or K light chains, consistent with a monoclonal plasma cell population. The majority of tumors expressed lambda light chains, consistent with previously reported canine plasma cell dyscrasias. Thioflavine T cytoplasmic fluorescence was seen in the majority (18/29) of plasmacytomas and with inflammatory plasma cells present in control specimens. Other round cell neoplasms (lymphosarcoma, histiocytoma, and mastocytoma) were negative with thioflavine T, indicating that positive staining with thioflavine T was specific for plasma cells (neoplastic and inflammatory). This study confirms by immunohistochemistry that canine extramedullary plasmacytomas disproportionately express lambda light chains and establishes thioflavine T staining as a rapid histochemical method for diagnosis of these tumors. PMID- 1911999 TI - Copper toxicosis in two herds of beef calves following injection with copper disodium edetate. PMID- 1912000 TI - Adenocarcinoma of the salivary gland in a beluga whale (Delphinapterus leucas). PMID- 1912001 TI - Diagnostic characteristics of bovine spongiform encephalopathy. PMID- 1912002 TI - Modeling experimental time series with ordinary differential equations. AB - Recently some methods have been presented to extract ordinary differential equations (ODE) directly from an experimental time series. Here, we introduce a new method to find an ODE which models both the short time and the long time dynamics. The experimental data are represented in a state space and the corresponding flow vectors are approximated by polynomials of the state vector components. We apply these methods both to simulated data and experimental data from human limb movements, which like many other biological systems can exhibit limit cycle dynamics. In systems with only one oscillator there is excellent agreement between the limit cycling displayed by the experimental system and the reconstructed model, even if the data are very noisy. Furthermore, we study systems of two coupled limit cycle oscillators. There, a reconstruction was only successful for data with a sufficiently long transient trajectory and relatively low noise level. PMID- 1912003 TI - Neurodynamics with spatial self-organizations. AB - A neural network architecture with self-organization in phase and actual space is proposed and discussed. Special type of differential local interconnections simulating diffusion, dispersion, and convection were investigated. It is shown that these interconnections are responsible for biological pattern formation in a homogeneous neural structure. The model suggests a phenomenological explanation of the mechanisms of edge detection in vision process. PMID- 1912004 TI - On the computational architecture of the neocortex. I. The role of the thalamo cortical loop. AB - This paper proposes that each area of the cortex carries on its calculations with the active participation of a nucleus in the thalamus with which it is reciprocally and topographically connected. Each cortical area is responsible for maintaining and updating the organism's knowledge of a specific aspect of the world, ranging from low level raw data to high level abstract representations, and involving interpreting stimuli and generating actions. In doing this, it will draw on multiple sources of expertise, learned from experience, creating multiple, often conflicting, hypotheses which are integrated by the action of the thalamic neurons and then sent back to the standard input layer of the cortex. Thus this nucleus plays the role of an 'active blackboard' on which the current best reconstruction of some aspect of the world is always displayed. Evidence for this theory is reviewed and experimental tests are proposed. A sequel to this paper will discuss the cortico-cortical loops and propose quite different computational roles for them. PMID- 1912005 TI - A computer based model for realistic simulations of neural networks. I. The single neuron and synaptic interaction. AB - The use of computer simulations as a neurophysiological tool creates new possibilities to understand complex systems and to test whether a given model can explain experimental findings. Simulations, however, require a detailed specification of the model, including the nerve cell action potential and synaptic transmission. We describe a neuron model of intermediate complexity, with a small number of compartments representing the soma and the dendritic tree, and equipped with Na+, K+, Ca2+, and Ca2+ dependent K+ channels. Conductance changes in the different compartments are used to model conventional excitatory and inhibitory synaptic interactions. Voltage dependent NMDA-receptor channels are also included, and influence both the electrical conductance and the inflow of Ca2+ ions. This neuron model has been designed for the analysis of neural networks and specifically for the simulation of the network generating locomotion in a simple vertebrate, the lamprey. By assigning experimentally established properties to the simulated cells and their synapses, it has been possible to verify the sufficiency of these properties to account for a number of experimental findings of the network in operation. The model is, however, sufficiently general to be useful for realistic simulation also of other neural systems. PMID- 1912006 TI - Phase transition theory for abnormal ocular dominance column formation. AB - A thermodynamic theory has previously been introduced for explaining the formation of ocular dominance columns in the visual cortex. This paper extends the theory to account for the variation in patterns of ocular dominance columns as a phase transition phenomenon. For this purpose, an "Order parameter" is calculated by Monte Carlo simulation. On a phase diagram representing a two dimensional parameter space, the conditions in which abnormal ocular dominance columns arise are visualized, and several visual deprivation experiments are successfully explained. PMID- 1912007 TI - Linear systems analysis of the relationship between firing of deep cerebellar neurons and the classically conditioned nictitating membrane response in rabbits. AB - The correlation of the activity of neurons in the interposed and dentate nuclei of the cerebellum with conditioned movements of the nictitating membrane was investigated using linear systems analysis. The activity of single deep cerebellar nuclear cells was assumed to be the input to a linear system that produced nictitating membrane movement. Data were initially analyzed with a causal model to assess the degree to which past neural activity predicted the conditioned response. 55 of 165 cells had correlation coefficients of 0.50 or greater between the model's moment-to-moment output and the actual output, with two interpositus cells having correlation coefficients of greater than 0.90. Double-sided impulse responses indicated that afference from the face and efference copy probably affect deep cerebellar neural activity. Nonlinearities were also found in the relationship between neuronal activity and conditioned movement. It was concluded that cerebellar deep nuclear firing is highly correlated with future nictitating membrane movements but that the firing movement relationship contains noncausal and nonlinear components. PMID- 1912008 TI - Self-organized control of bipedal locomotion by neural oscillators in unpredictable environment. AB - A new principle of sensorimotor control of legged locomotion in an unpredictable environment is proposed on the basis of neurophysiological knowledge and a theory of nonlinear dynamics. Stable and flexible locomotion is realized as a global limit cycle generated by a global entrainment between the rhythmic activities of a nervous system composed of coupled neural oscillators and the rhythmic movements of a musculo-skeletal system including interaction with its environment. Coordinated movements are generated not by slaving to an explicit representation of the precise trajectories of the movement of each part but by dynamic interactions among the nervous system, the musculo-skeletal system and the environment. The performance of a bipedal model based on the above principle was investigated by computer simulation. Walking movements stable to mechanical perturbations and to environmental changes were obtained. Moreover, the model generated not only the walking movement but also the running movement by changing a single parameter nonspecific to the movement. The transitions between the gait patterns occurred with hysteresis. PMID- 1912009 TI - Altering the synchrony of stimulus trace processes: tests of a neural-network model. AB - A previously described neural-network model (Desmond 1991; Desmond and Moore 1988; Moore et al. 1989) predicts that both CS-onset-evoked and CS-offset-evoked stimulus trace processes acquire associative strength during classical conditioning, and that CR waveforms can be altered by manipulating the time at which the processes are activated. In a trace conditioning paradigm, where CS offset precedes US onset, the model predicts that onset and offset traces act in synchrony to generate unimodal CR waveforms. However, if the CS duration is subsequently lengthened on CS-alone probe trials, the model predicts that onset and offset traces will asynchronously contribute to CR output and bimodal CRs will be generated. In a delay conditioning paradigm, in which US onset occurs prior to CS offset, the model predicts that only the onset process will gain associative strength, and hence, only unimodal CRs will occur. Using the rabbit conditioned nictitating membrane response preparation, we found experimental support for these predictions. PMID- 1912010 TI - Minimum mean square error estimation of connectivity in biological neural networks. AB - A minimum mean square error (MMSE) estimation scheme is employed to identify the synaptic connectivity in neural networks. This new approach can substantially reduce the amount of data and the computational cost involved in the conventional correlation methods, and is suitable for both nonstationary and stationary neuronal firings. Two algorithms are proposed to estimate the synaptic connectivities recursively, one for nonlinear filtering, the other for linear filtering. In addition, the lower and upper bounds for the MMSE estimator are determined. It is shown that the estimators are consistent in quadratic mean. We also demonstrate that the conventional cross-interval histogram is an asymptotic linear MMSE estimator with an inappropriate initial value. Finally, simulations of both nonlinear and linear (Kalman filter) estimate demonstrate that the true connectivity values are approached asymptotically. PMID- 1912011 TI - Intracellular nonlinear frequency response measurements in the cockroach tactile spine neuron. AB - The threshold of the cockroach tactile neuron increases strongly with depolarization by a process involving at least two time constants. This effect is probably responsible for the rapid and complete adaptation of the neuron's response to step inputs. A technique for intracellular recording and stimulation of the neuron has recently been established and this allows direct observation of the dynamic response of the neuronal encoder. A white noise stimulus was used to modulate the membrane potential of the neuron. The first-order frequency response function between membrane potential and action potential discharge could be explained by a variable threshold model with two time constants. Second-order frequency response functions could be accounted for by a Wiener cascade model. The dynamic nonlinear behavior of the encoder can therefore be explained by a unidirectional threshold which increases linearly and dynamically with membrane potential. PMID- 1912013 TI - A new method of the description of the information flow in the brain structures. AB - The paper describes the method of determining direction and frequency content of the brain activity flow. The method was formulated in the framework of the AR model. The transfer function matrix was found for multichannel EEG process. Elements of this matrix, properly normalized, appeared to be good estimators of the propagation direction and spectral properties of the investigated signals. Simulation experiments have shown that the estimator proposed by us unequivocally reveals the direction of the signal flow and is able to distinguish between direct and indirect transfer of information. The method was applied to the signals recorded in the brain structures of the experimental animals and also to the human normal and epileptic EEG. The sensitivity of the method and its usefulness in the neurological and clinical applications was demonstrated. PMID- 1912012 TI - A computational model of the vertical anatomical organization of primary visual cortex. AB - A method for modeling anatomical connectivity for a vertically organized slab of cortical tissue in mammalian primary visual cortex has been developed. The modeled slab covers 500 x 500 microns of cortical surface and extends vertically throughout the full depth of the cortex. The model slab was divided into 6 laminae and neuronal somata were distributed in three dimensions through the slab in accordance with experimentally derived cell densities. Axonal and dendritic arborizations were modeled as line segments. A total of 17 morphological types of neurons were included. Connectivity was established based on proximity between axonal and dendritic arbors. There is good general agreement between the vertical distribution of connections generated by the model and the vertical distribution of synapses observed for cat area 17. In all layers, fewer connections were generated in the model than synapses in cat area 17. This is due, at least in part, to the exclusion of long range intracortical projections and sources of afferent input other than the dorsal lateral geniculate nucleus from the model. The connection scheme described here will be used in conjunction with a physiology model to model vertical signal flow, and will be expanded further to model receptive fields of cortical neurons. PMID- 1912014 TI - Seeking the magic bullet. PMID- 1912015 TI - Treatment of Pseudomonas infections in peritoneal dialysis patients. AB - Pseudomonas species infections in the peritoneal dialysis population consist primarily of peritonitis or exit site infections. These organisms have traditionally proven difficult to eradicate, and the standard antibiotic regimen has carried the potential for nephrotoxicity. At our institution, all peritoneal dialysis patients with Pseudomonas exit site infections or peritonitis were treated with an antibiotic combination of intraperitoneal ceftazidime and oral ciprofloxacin. Treatment duration was dependent upon the site of infection. Recurrent exit site infections were treated with a repeated course of the antibiotics, and with surgical debridement and subsequent shaving of the external cuff of double-cuffed catheters. We saw a total of 11 Pseudomonas aeruginosa exit site infections in 7 patients (4 recurrent). Patients with recurrent infections were subsequently cured with the regimen as outlined above. Of 7 patients with Pseudomonas species peritonitis (aeruginosa, fluorescens, stutszeri, and maltophilia), 5 were cured with the initial antibiotic regimen. The 2 failures were both infected with Pseudomonas maltophilia, which is consistent with observed organism sensitivity data. The combination of ceftazidime and ciprofloxacin with the option for surgical debridement of the external cuff (in exit site infections) appears effective in the treatment of Pseudomonas species infections in the peritoneal dialysis population. Sensitivity data should be used to adjust the antibiotic regimen when appropriate. PMID- 1912016 TI - A new stable bicarbonate dialysis solution for peritoneal dialysis: preliminary report. AB - This paper describes the use of glycylglycine to prepare dialysis solution containing bicarbonate, calcium and magnesium. Bicarbonate with glycylglycine form a buffer with a constant pH of 7.35, which prevents reaction with calcium or magnesium and the formation of insoluble carbonate salts. This bicarbonate-based solution is stable over long periods and can be used with the same simplicity and convenience as lactate solution for peritoneal dialysis (PD) in humans. PMID- 1912017 TI - Stimulation of mesothelial cells proliferation by endogenous growth factor(s). AB - We have attempted to determine whether human mesothelial cells (MC) have the power to influence their own proliferation. A serum-free medium was conditioned with the mesothelial monolayer for 24 hours and then applied to proliferating MC. Conditioned medium increased proliferation rate of MC. When the medium was heated at 60 degrees C for 60 minutes, the growth-promoting activity of the conditioned medium decreased by 50%, suggesting that MC produce at least 2 growth factors, 1 heat-labile and the other heat-stable. When MC were exposed continuously to a medium containing 90 mM glucose growth factor, production was decreased by 35%. However, when the cells were exposed to glucose only on alternate days, growth factor production was similar to that in the control medium. On the other hand, MC exposed continuously for 10 days to 90 mM of glucose exhibited a weaker response to endogenous growth factor, even in a normotonic medium with low glucose concentration. Our results suggest that MC synthesize factor(s), which stimulate their own proliferation, and that high glucose concentrations interfere with this production and the subsequent action of growth factor. PMID- 1912018 TI - Ciprofloxacin in the treatment of gram-positive bacterial peritonitis in patients undergoing CAPD. AB - Fluoroquinolones may be a good alternative for the treatment of bacterial peritonitis in patients undergoing continuous ambulatory peritonitis dialysis (CAPD). To test their efficiency against Gram-positive bacteria, we treated with intraperitoneal (i.p.) ciprofloxac in 30 episodes of Gram-positive bacterial peritonitis without manifest tunnel infection of the peritoneal catheters. Treatment was sustained for 5 days, then orally for 10 further days. Clinical and bacteriological responses were satisfactory in 25 cases, but resolution of infection was slow in 5 cases of Staphylococcus aureus. The minimal inhibitory and bactericidal concentrations were 0.0625-0.50 and 0.125-1.0 micrograms/mL respectively, lower than the plasma and dialysate concentrations of the drug. Side effects were negligible. We conclude that ciprofloxacin provides a good therapeutic alternative to more widely used antibiotics for the empirical treatment of peritonitis in patients undergoing CAPD. However, combinations of antibiotics may be necessary, in Staphylococcus aureus peritonitis. PMID- 1912019 TI - Morphology of peritoneal dialysis catheter tunnel: macroscopy and light microscopy. AB - There is scanty knowledge of the morphology of peritoneal dialysis catheter tunnels in humans, even though such knowledge may impact on peritoneal catheter design, implantation and postimplantation care. Past descriptions of catheter tunnels are based mainly on data from animal experiments. Based on these data, it has been assumed that epidermal spreading is inhibited by collagen fibers ingrown into the cuff. Our preliminary investigation indicated that this may not be the case in humans and led us to study catheter tunnel morphology in more detail. Eighteen catheter tunnels (2-5mm of tissue around the catheters) were removed in 17 peritoneal dialysis patients. The catheters were inserted 30 to 2013 days prior to removal (median 366 days). The catheters were removed electively or because of infectious or noninfectious complications. Contrary to the observations in animals, in only 1 case did epithelium extend to the cuff with only a minimal amount of granulation tissue present at the end of a 9 mm long sinus tract. In the remaining cases, the leading edge of the epithelium always met granulation tissue 1-14 mm from the exit, and the cuffs were found 8-33 mm from the exit. In tunnels older than 197 days, dense fibrous tissue was ingrown into the cuffs, and a dense fibrous capsule surrounded the cuff. The uninfected intercuff segment formed a pseudosheath, indistinguishable from a tendon sheath or synovial membrane. Infection in the catheter tunnel propagates through the part of the cuff adjacent to the tubing inside the capsule, suggesting that the cuff per se does not constitute a major barrier for spreading infection. This observation, by exclusion, infers that the beneficial role of an external cuff in decreasing exit infections is by providing firm anchorage of the catheter resulting in restriction of its piston like movement and thereby minimizing trauma and inward conveyance of outer sinus tract flora. PMID- 1912020 TI - Peritoneal catheter tip location during non-complicated continuous ambulatory peritoneal dialysis. AB - In the present study, we evaluated the relationship between 1. the volume and rate of dialysis outflow and subsequent inflow, 2. the patient's impression of the location of the catheter tip and 3. the stability of the catheter tip location. Thirteen patients were studied on 2 random occasions (periods 1 and 2). Inflow (L/min) was significantly faster than outflow (p less than 0.05). No catheter tips were located in the far upper part of the abdomen. Outflow with the catheter tip located in the middle part of the abdomen was significantly lower than with the tip located in the inferior quadrants (p less than 0.02). Two patients were able to feel the catheter tip at Period 1, and 4 at Period 2, but only 1 patient was able to state the exact location identical to fluoroscopy. Ninety-two percent of the fluoroscopic evaluations showed catheter tips located in the same anatomical regions in upright as well as supine positions. If vertical "neighbour" anatomical regions were included in the evaluation of the catheter tip migrations, all catheter tips were located at the same or the vertical "neighbour" region in the 2 study periods. PMID- 1912021 TI - Functional characteristics of peritoneal macrophages of renal failure patients on peritoneal dialysis. AB - Functional activity of peritoneal macrophages of 50 patients with end-stage renal failure on intermittent peritoneal dialysis (IPD) and of 30 control subjects with normal renal function was determined. Phagocytosis of latex particles by macrophages of dialyzed patients was significantly lower as compared with the controls. Further depression of the phagocytic activity was observed during bacterial peritonitis. Macrophages from the dialyzed patients also showed nonsignificantly decreased functional expression of Fc receptors (FcR) and increased spontaneous nitro blue tetrazolium (NBT) reduction. PMID- 1912022 TI - Increased salivary concentration of human epidermal growth factor in patients undergoing CAPD. AB - Epidermal growth factor (EGF) was measured in the saliva of 36 patients with chronic renal failure (CRF) and 29 matched control subjects. Salivary EGF in controls was 0.65 +/- 0.009 nmol/L compared with 0.99 +/- 0.24 nmol/L in nondialyzed CRF patients, 1.15 +/- 0.23 in hemodialyzed patients and 1.96 +/- 0.25 (p less than 0.01, Wilcoxon Rank Sum Test) in CAPD-treated patients. On Sephadex chromatography, the major peak of immunoreactive EGF from patient and control saliva samples coeluted with purified human EGF. We conclude that salivary concentrations of human EGF are significantly elevated in end-stage renal failure, particularly in patients treated by CAPD. PMID- 1912023 TI - Initiatives in peritoneal dialysis: where do we go from here? AB - In 1989, a conference was held to discuss the current status of technique survival for patients treated with continuous ambulatory peritoneal dialysis (CAPD). Major reasons for patient drop-out from CAPD-peritonitis, inadequate dialysis, catheter-related problems and psychosocial factors-were reviewed, as were constructive techniques for dealing with these problems and areas for future investigation. PMID- 1912024 TI - Sclerosing encapsulating peritonitis once again. PMID- 1912025 TI - Long-term, intraperitoneal vancomycin in the prevention of recurrent peritonitis during CAPD: preliminary results. PMID- 1912026 TI - Diagnosis of hydrothorax-complicating CAPD and demonstration of successful therapy by scintigraphy. PMID- 1912027 TI - Vaginal leak of peritoneal dialysis liquid. PMID- 1912028 TI - Literature. July-September 1991. PMID- 1912029 TI - Incidence and clinical risk factors for bleeding and thrombotic complications in myeloproliferative disorders. A retrospective analysis of 260 patients. AB - Bleeding and thrombosis are frequent complications in myeloproliferative disorders (MPD) and are associated with severe organ damage and a high mortality. Elevated platelet count, elevated hematocrit, and patient age are regarded as risk factors for bleeding and thromboembolic events in MPD, although the significance of these parameters was not confirmed by clinical studies. We retrospectively analyzed vascular complications in 260 patients with MPD and tried to identify parameters predictive for bleeding and thrombembolic events. Our cohort consisted of 115 patients with chronic myeloid leukemia (CML), 84 patients with polycythemia vera (PV), 26 with essential thrombocythemia (ET), 25 with osteomyelofibrosis (OMF), and 10 patients with unclassifiable MPD. During a median follow-up period of 31 months, 126 patients with chronic MPD suffered bleeding or thrombotic events. Bleeding was observed in 57% of patients with OMF, 23% with PV, 20% with chronic phase CML, and 16% with ET. Thrombotic events were most common in patients with PV (36% of patients), followed by ET, OMF, and chronic phase CML (20%, 17%, and 6% of patients, respectively). Recurrent thrombotic episodes frequently occurred in patients with PV and ET, whereas patients with OMF often had more than one bleeding event. Thirty patients died of thrombohemorrhagic complications during follow-up. Multivariate analysis, including all patients with chronic MPD, revealed that elevated red blood cell count, higher hemoglobin level, and increased percentage of segmented neutrophils at the time of diagnosis were associated with thrombosis, whereas patients with bleeding complications were characterized by low red cell count, lower hemoglobin, and a lower percentage of segmented neutrophils. However, when analyzed by MPD subgroup, none of these parameters retained a predictive value for bleeding or thrombotic events. Moreover, elevated platelet count and patient age were not risk factors for bleeding complications. Thrombotic events were less frequent in patients below the age of 40, and were increased in patients aged 70 and above. However, this was primarily due to the high percentage of elderly patients in subgroups mainly affected by thrombosis (PV and ET). In most MPD subgroups, the rate of bleeding and thrombosis was highest just before and during the first months after diagnosis, and declined thereafter. Thrombohemorrhagic complications were less frequent after phlebotomy in PV and after therapy with alkylating agents in CML. The institution of cytoreductive therapy soon after the diagnosis was made may explain the reduced incidence of complications later in the disease. We conclude that morbidity and mortality from thrombohemorrhagic complications are high in myeloproliferative disorders.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1912031 TI - Dermatomyositis as presenting symptom of Hodgkin's disease. AB - The association between dermatomyositis and malignancy is well documented. However, the association between dermatomyositis and Hodgkin's disease is very unusual, particularly in children, adolescents, and young adults. A MEDLINE search of the literature revealed only 13 previous cases. PMID- 1912030 TI - X-linked thrombocytopenia and Wiskott-Aldrich syndrome: similar regional assignment but distinct X-inactivation pattern in carriers. AB - While inherited X-linked (XL) isolated thrombocytopenia is a mild condition, the Wiskott-Aldrich syndrome (WAS) associates severe thrombocytopenia with an immunodeficiency component and has a poor prognosis. Whether these conditions correspond to separate genetic entities or to different mutations of the same gene(s) remains unresolved. The Wiskott-Aldrich syndrome locus has been assigned to Xp 11.2 by means of RFLP studies. The X-inactivation pattern in female carriers has been found to follow a skewed pattern in the hematopoietic cells, thus allowing carrier detection. We studied a family with four members affected by XL thrombocytopenia and report the results of genetic segregation analysis, together with the X-inactivation pattern of hematopoietic cells from an obligate female carrier. Although the affected locus mapped to the same region as that of WAS, lymphocytes presented a skewed pattern of X-inactivation, whereas polymorphonuclear lymphocytes (PMN) did not. These results provide further evidence that the Wiskott-Aldrich syndrome and XL thrombocytopenia are different expressions of mutations within a single locus and that the severity of the disease corresponds to distinct hematopoietic cell selections in obligate carriers. PMID- 1912032 TI - Acquired bleeding disorder in a patient with congenital factor VII deficiency. PMID- 1912034 TI - High-dose IgG for neutropenic patients with acquired immunodeficiency syndrome (AIDS). AB - Leukocytopenia and bacterial infections are common and serious complications in patients with AIDS. We report here on three patients in whom the administration of high IgG doses led to gradual (two patients) or prompt (one patient) increases in circulating leukocyte counts (from 200-600 to 2500-5900/microliters), inducing definite improvement in two patients; one patient died from Pneumocystis carinii pneumonia. Although the rise in leukocyte counts lasted for only approximately 3 weeks, high-dose IgG might be a useful therapeutic adjunct in such patients. PMID- 1912033 TI - Hirudin, a new therapeutic tool? AB - Hirudin is the most potent natural inhibitor of thrombin known to date. It is gaining popularity as an anticoagulant now that recombinant and synthesized forms are available. It is a monospecific and co-factor-independent thrombin inhibitor with otherwise inert pharmacological properties. Being a surprisingly weak immunogen, its administration has exhibited no side effects, particularly on platelets. Bleeding complications are not to be expected at therapeutic doses. Effective anticoagulatory doses can be easily predicted and laboratory control is no problem. Application of hirudin or derivatives thereof may be indicated for: prophylaxis and treatment of postoperative venous thrombosis and diffuse microthrombosis; prevention of arterial thrombosis, especially in cardiac surgery; enhancement of fibrinolytic therapy and/or angioplasty to prevent reocclusion; extracorporeal circulation; and plastic surgery. Hirudin may be a particularly useful alternative anticoagulatory agent in patients sensitized to heparin or in patients with hereditary or acquired antithrombin III deficiency. However, whether hirudin is really an effective therapeutic tool and whether it can replace heparin in certain clinical indications can be judged only after extended clinical experience has been accumulated. PMID- 1912035 TI - Effects of low-dose mafosfamid on the lymphokine-activated killer cell activity of peripheral blood mononuclear cells determined by a clonogenic microassay. AB - The effects of mafosfamid on lymphokine-activated killer (LAK) cells were examined, using a newly developed clonogenic microassay with tumor target cells instead of the common 51Cr release. When nonadherent peripheral blood mononuclear effector cells were exposed to 1 x 10(-9) or 1 x 10(-8) M mafosfamid 1 h prior to activation with interleukin 2 (IL-2), LAK-cell activity increased, resulting in fewer colonies of human KB squamous carcinoma cells than without mafosfamid treatment. In contrast, when effector cells were exposed to mafosfamid after IL-2 activation LAK-cell activity was inhibited. Notably, the in vitro immunomodulatory effects of mafosfamid were detected at concentrations 100-1000 times below those shown to be cytotoxic. Although the mechanisms remain to be elucidated, our results might be an in vitro representation of the known in vivo immunostimulation of low doses of cyclophosphamide. PMID- 1912036 TI - Patterns of infection in 41 patients with idiosyncratic drug-induced agranulocytosis. AB - We examined the patterns of infection in 41 consecutive patients with idiosyncratic drug-induced agranulocytosis observed during the past 15 years. All patients were nursed in reverse isolation and treated prophylactically with oral antimicrobials and antifungal compounds. Nine of 41 patients remained without fever and did not need any parenteral antibiotic treatment for full recovery. The other 32 patients developed fever during the period of agranulocytosis and were treated with empirical antimicrobial therapy. Febrile episodes were documented microbiologically in 16 patients (eight with and eight without bacteremia) and clinically in six patients. In the other ten cases the fever was of unexplained origin. The observed pattern of infection was in accordance with the type of infection as reported in cancer patients during the granulocytopenic phase induced by cytotoxic drugs. Ten of 32 febrile patients showed improvement after empirical antimicrobial therapy, whereas three patients died, two of them of a lower respiratory tract infection and one of a massive hemorrhage due to necrosis of the carotid artery. In ten patients the signs and symptoms of infection resolved only after adjustment of the initial empirical scheme. In nine patients the fever persisted even after additional empirical antifungal therapy but subsided after recovery of the granulocytopenia. PMID- 1912038 TI - Multiple comparisons? No problem! PMID- 1912037 TI - Treatment of severe aplastic anemia with antilymphocyte globulin and androgens: a report on 33 patients. AB - Thirty-three patients with severe aplastic anemia were treated with antilymphocyte globulin (ALG, Merieux) and androgens (with or without corticosteroids) between 1981 and 1989; 24 patients (72.7%) were responders after one course of ALG, eight were nonresponders, and only one patient had an early death. Eighteen of the 24 responses occurred within 2 months of ALG treatment. Of note is the good response rate we obtained for very severe aplastic anemia (four responders of five evaluable patients). With a median follow-up of 36 months (range 1-97), a survival rate of 77.6% +/- 1.2% was obtained at 30 months. No predictive factor of survival could be identified except response to treatment (p = 0.0001). The duration of the disease before treatment was inversely related to survival, although this difference did not reach statistical significance (p = 0.06). Four initial responders relapsed after 14, 24, 38, and 57 months. Three of these patients received a second course of ALG and two responded. In contrast, four of the non-responders received a second course of ALG, with only one response. Toxicity of androgens was mild. No patient developed a PNH clone or myelodysplastic syndrome. Major toxicity of corticosteroids was femoral osteonecrosis in three patients. In our experience, the combination of ALG and androgens in SAA, with or without corticosteroids, was associated with a higher response rate and better survival than in many previously published reports. This could have been due to the intensive supportive care during the initial weeks of treatment. We suggest that it may also result from the addition of androgens to ALG, although this issue may only be resolved in a randomized study. PMID- 1912039 TI - Empirical-Bayes adjustments for multiple comparisons are sometimes useful. AB - Rothman (Epidemiology 1990;1:43-46) recommends against adjustments for multiple comparisons. Implicit in his recommendation, however, is an assumption that the sole objective of the data analysis is to report and scientifically interpret the data. We concur with his recommendation when this assumption is correct and one is willing to abandon frequentist interpretations of the summary statistics. Nevertheless, there are situations in which an additional or even primary goal of analysis is to reach a set of decisions based on the data. In such situations, Bayes and empirical-Bayes adjustments can provide a better basis for the decisions than conventional procedures. PMID- 1912040 TI - Trends in suicide mortality among the elderly in Norway, 1966-1986. AB - Increasing suicide rates among the oldest segments of the population, together with the increasing proportion of elderly in Western countries are sources of growing concern. I analyzed suicide trends among the elderly in Norway during the period 1966-1986. I used Poisson regression to analyze time trends on the basis of age, calendar period, and birth cohorts. Age and period affected the suicide rates for both sexes more than did cohort effects. Specific age-sex groups preferred specific methods of suicide. PMID- 1912041 TI - An epidemiologic approach to the study of acute reversible health effects in the workplace. AB - We present an epidemiologic approach for the study of the irritant effects of sodium borate exposure that can be used to study acute reversible health effects more generally. Acute irritant responses, such as symptoms of nasal irritation or cough, are subjective. They may, however, be accompanied by transient airway obstruction, which can be objectively measured by a change in peak expiratory flow (PEF) or forced expiratory volume in one second (FEV1). Because these physiologic responses are reversible and follow short-term peaks of exposure, they cannot be studied effectively using conventional epidemiologic methods of design and analysis. The proposed study design is a short-term prospective cohort study with frequently repeated measures of health effects and simultaneous measures of exposure. Because each subject passes through periods of high and low short-term exposure, the study has the form of a crossover design. This design permits each acute response to be linked to the corresponding short-term average exposure, providing the data necessary for dose-response analyses within subject. We present the results of the sodium borate study to illustrate the analysis of such data. PMID- 1912042 TI - Conditions other than underlying cause of death listed on death certificates provide additional useful information for epidemiologic research. AB - Conditions other than underlying cause of death listed on death certificates may provide useful information for epidemiologic research. We explored this possibility for any mention of diabetes, renal diseases, and pneumonia-influenza bronchitis on death certificates from the Chicago Western Electric Study. When we used any mention, sufficient numbers of deaths for analyses of risk factor associations with diabetes (N = 47), renal diseases (N = 25), and pneumonia influenza-bronchitis (N = 59) were available; analyses for these risk factors were not possible using underlying cause of death alone (N = 3, 6, and 16, respectively). Using Cox regression, we observed positive associations of age, systolic blood pressure, serum cholesterol, body mass index, and cigarettes smoked per day with any mention of diabetes or renal disease. Age, systolic blood pressure, and cigarettes smoked per day were positively related to any mention of pneumonia-influenza-bronchitis; serum cholesterol and body mass index were inversely related to this endpoint. Whether we identified cardiovascular disease deaths using underlying cause, other mention, or any mention, the relations of established major risk factors with 25-year mortality were similar. PMID- 1912043 TI - Heterogeneity of the effect of family history on breast cancer risk. AB - We studied the effects of family history on breast cancer risk among 2,908 cases and 3,180 controls, selected from participants in a nationwide screening project. First-degree family history was associated with a twofold risk increase. Second degree family history effects were minimal, after adjusting for effects of first degree relatives. Family history effects were not confounded by age at menarche, age at first full-term birth, age at natural menopause, or previous benign breast disease. Risks from mother's and sister's history were independent. The odds ratio (OR) from a maternal history, 1.9 (95% confidence interval [CI]: 1.6-2.3), varied little by the subject's age at diagnosis, menopause status, or disease laterality. Interactions of maternal history effects with multiple breast biopsies and age at menopause were greater than additive, indicating common mechanistic pathways. The OR from a sister's history was 2.3 (95% CI: 1.9-2.8) and was increased among women who were less than 45 (OR = 6.9), had bilateral disease (OR = 4.7), or were premenopausal (OR = 4.4). The effects from a mother's history and a sister's history are modified in different directions by different factors, providing further indication of the separate roles of a mother's and sister's history in breast cancer etiology. PMID- 1912044 TI - Breast cancer mortality and the change in fertility risk factors at menopause: a prospective study of 800,000 married Norwegian women. AB - I examined breast cancer mortality in relation to fertility factors in a cohort of 800,814 married Norwegian women aged 25-74 years at the start of follow-up. Women aged 25-44 years with a first birth after the age of 35 years had a RR = 2.58 compared with women with a first birth before the age of 20 years. For women aged 45-74 years, the corresponding RR was 1.35. On the other hand, the rate differences between women with a late first birth (35+ years) and an early birth (less than 20 years) were similar for women of different ages. Small rate differences were found for premenopausal women between uniparous women and women with 6-7 children, but postmenopausal women with many children had lower rates of breast cancer mortality than uniparous women. For postmenopausal women the rate differences were stable over age categories. This study points toward a change in fertility risk factors at menopause. PMID- 1912045 TI - Risk indicators for talipes equinovarus in Washington State, 1987-1989. AB - To identify risk indicators for talipes equinovarus, we compared 175 case children with talipes equinovarus of unknown etiology identified through the Washington State Birth Defect Registry with 1,470 control children sampled from resident live births. Infant gender, maternal smoking, death of a preterm sibling, and marital status were independently related to talipes equinovarus in an analysis based on information from birth certificate records. The findings differed by infant gender. The prevalence odds ratio for maternal smoking was 2.6 (95% confidence interval: 1.6-4.0) in males and 1.4 (95% confidence interval:0.6 3.2) in females. PMID- 1912046 TI - Risk factors for cervical carcinoma: does detection bias play a role? AB - We explored the impact of detection bias on cervical carcinoma risk factors in a population-based case-control study in Utah. Risk estimates for most cervical carcinoma risk factors were virtually the same in women who reported frequent Pap tests as those obtained from the population at large. Women who reported infrequent Pap tests, however, had higher estimates of risk than the general population. The largest difference was observed for those who used frequent vaginal douching, where a risk estimate of 9.5 was observed among women who reported infrequent Pap tests compared with 2.7 for women who reported frequent Pap tests. PMID- 1912047 TI - Validation of a three-month physical activity recall questionnaire with a seven day food intake and physical activity diary. AB - We assessed the validity of a three-month physical activity questionnaire. The validation instrument was a seven-day self-report diary of physical activity and food intake, given to 113 randomly selected persons. We obtained Spearman correlations of 0.60, 0.48, and 0.91 and kappa scores of 0.36, 0.23, and 0.62 from the physical activity recall and diary for moderate, vigorous, and total activity. We conclude that the three-month recall questionnaire reasonably reflects activity in this community-based sample. PMID- 1912048 TI - Alcohol drinking and mortality. PMID- 1912049 TI - Miscarriage, caffeine, and the epiphenomena of pregnancy: the causal model. PMID- 1912050 TI - Time trends in leisure-time physical activity: another perspective. PMID- 1912051 TI - Reported measles immunisation and serological immunity in children attending general practitioners. AB - To determine the feasibility of serological testing for measles immunity in children attending general practitioners and to assess the validity of establishing immune status by reported immunisation history compared with serology, a cross-sectional descriptive study was conducted in general practices in the Illawarra area south of Sydney, New South Wales. Participants were 234 children under 15 years attending general practitioners. 87 per cent of children were reported to have been immunised against measles, but 46 per cent of these children were seronegative for measles antibody using an ELISA test on finger prick blood. This could not be explained by inaccurate reporting of immunisation. No causes other than failure to seroconvert or inadequate specificity of the test on the blood samples were evident. Failure to seroconvert as a result of inadequate adherence to cold chain requirements is a possibility that needs further investigation. The results further question whether a single vaccination is adequate to achieve the public health aims of measles immunisation programs. PMID- 1912052 TI - Community knowledge, attitudes and media recall about AIDS, Sydney 1988 and 1989. AB - A randomized telephone survey of Sydney residents aged 16-50 was conducted in 1988 (n = 651) and repeated in 1989 (n = 701) to assess changes in AIDS-related knowledge and attitudes and opinions about AIDS policies. The mean number of correct answers to 21 questions about AIDS was 18.6 (1988) and 18.1 (1989). Almost all respondents gave correct answers to fundamental questions about AIDS transmission and prevention. No statistically significant changes in AIDS knowledge were found between the two survey periods. There was widespread anxiety about AIDS: just over half the population was personally afraid of getting AIDS, 80 per cent had considered being tested for human immunodeficiency virus and over half supported 'compulsory testing' for all the population. Mass media messages about AIDS were almost universally recalled, with the Grim Reaper and news stories centring on particular individuals ranking highest. AIDS policy makers in public education should consider the wisdom of continuing to target messages to low-risk populations. These messages have raised fundamental knowledge about AIDS but may be unintentionally causing social divisiveness and widespread unnecessary anxiety. PMID- 1912053 TI - Factors associated with successful risk reduction after a community coronary risk factor screen. AB - Debate continues over the effectiveness of coronary risk factor screening as a strategy for the prevention of coronary heart disease in the community. We reviewed changes in risk factors one year after a community coronary risk factor screen and found highly significant reductions in the blood cholesterol (mean reduction of 0.6 mmol/l) and body mass index (mean reduction of 1.03 kg/m2) in those participants who at the initial screening were found to have elevated (greater than 6.5 mmol/l) blood cholesterol concentrations. Comparison of this group with a reference group not given health advice and a group of hypercholesterolaemic clinic attenders showed that the blood cholesterol reduction could not be accounted for solely by regression to the mean, and was as good as the blood cholesterol reduction achieved by regular clinic attendance. Although there were many factors that could account for these reductions, we found that participants who received risk factor measurement and counselling during the screening process and who sought medical follow-up after the screen had a greater reduction in risk factors. PMID- 1912054 TI - The implementation of community-based crisis services for people with acute psychiatric illness. AB - This article describes three recently established community-based crisis services for people with acute psychiatric illness. Data were obtained from local information systems developed in the early phase of service operation. Patterns of service were found to vary among the teams in terms of the frequency of contact with the client, the period of contact with the client and the overall numbers of contacts. Such diversification of services reflects, at least in part, the differences in the service networks within which the new services were Such diversification of services is inevitable and creative, and the evaluation of these services must consider not only the short-term impact of crisis services, but also the impact of the network of care services on longer term outcomes for the client. PMID- 1912055 TI - Changes in smoking behaviour after a total workplace smoking ban. AB - This paper reports data on changes in smoking behaviour after the introduction of a total workplace smoking ban in Telecom Australia. A sample of 1089 Telecom staff were surveyed in the months before the introduction of the ban and 620 were resurveyed six months after the ban had been implemented. A further sample of 1424 was drawn from the same parts of the organisation 18 months after implementation. Among the smokers in these samples, the bans produced a reduction in workday cigarette consumption of between three and four cigarettes a day and this reduction was maintained at 18 months. Over the two-year period from six months before the ban to 18 months after it, smoking prevalence dropped about 5 per cent, which we estimate is about twice the decline found in the general community. Workplace smoking bans can produce public health and can assist individual smokers to regulate their habit. PMID- 1912056 TI - Solar protection issues for schools: policy, practice and recommendations. AB - This study presents findings on solar protection policies and practices in primary and secondary schools in New South Wales, Australia. The findings suggest that policies have been more fully articulated in primary schools than in secondary schools and that there is wide scope for further public health initiatives to protect children from the risk of skin cancer. Little attention has been given to the potential benefits of timetable changes and provision of shade in school environments, although school principals considered the latter would be a successful means of increasing protection. The level of solar education provided in the schools surveyed in our study was minimal, suggesting that urgent attention should be given to incorporating these issues in the school curriculum. Observations of school children's solar protection behaviours suggest that the majority of children used some form of protection in the middle of the day, but the form of protection changed with age. Consideration of more structural and environmental changes is needed to maximise the opportunities for solar protection in schools. PMID- 1912058 TI - A seven-point plan to explain regression to the mean. PMID- 1912057 TI - Overweight and television watching. AB - Recent work by several United States researchers has provided evidence of a direct correlation between obesity and hours of television viewing per day. This paper considers the association between obesity and hours of television viewing as well as the effect of various confounders on this association with an Australian population. A statistically significant association between amount of television viewing and overweight was found. However, the relatively small sample size and the subsequently wide confidence intervals preclude any firm conclusions. Health promotion efforts to encourage physical activity and to promote the prevention of ill health should be made in routine television programming. PMID- 1912059 TI - War and peace or do improvements in health services have to be constrained by incrementalism? PMID- 1912060 TI - Health consequences of the recession. PMID- 1912061 TI - Health economics in Australia. PMID- 1912062 TI - An element of dental health? Fluoride and dental disease in contemporary Australia. PMID- 1912063 TI - Aluminium in the drinking water--is it safe? PMID- 1912064 TI - Stomach cancer mortality in New South Wales and Sydney, 1980 to 1985. AB - Unit list mortality data for the period 1980-1985 are used to examine differential mortality from stomach cancer in New South Wales, with reference to age, marital status, occupational status and birthplace, and geographical variations in mortality in metropolitan Sydney. Ecological correlation and analysis of characteristics of persons dying in areas of high mortality in Sydney are undertaken to determine where populations at risk reside and whether different populations at risk inhabit particular areas, resulting in significantly higher mortality. This was found to be the case in certain areas and it appears that the immigrant population contributed considerably to mortality variation. The implications for health service provision and preventive measures are discussed. PMID- 1912065 TI - [Fusion of artificial lipid membranes induced by synthetic "fusion peptide" of arenaviruses]. AB - The fusing capacity of lipid membranes of a synthetic 23-member peptide was studied. This hydrophobic peptide represents an analog of a predicted functional site ("fusion peptide") of the GP2 envelope protein of the Lassa virus (family Arenaviridae). Fusion of small monolayer liposomes was detected by the method of resonance energy transfer between the fluorescent derivatives of the lipid, NBD PE (donor) and Rd-PE (acceptor). Using this peptide, the pH-dependent fusing activity was found in liposomes having different phospholipid composition. The rate and efficiency of liposome fusion increased with a decrease in pH and the lipid/peptide ratio as well as with a temperature increase. The increase in the ionic strength and Ca2+ concentration in the reaction mixture led to the inhibition of the peptide-induced fusion of liposomes. Neither the phospholipid charge, nor the transmembrane proton gradient of liposomes had any appreciable effect on the kinetics of the peptide-induced fusion. Neutralization of the medium in the course of the fusion reaction sharply decelerated, whereas repeated acidification activated this process. This finding suggests that peptide protonation plays a role in fusion reactions. It was suggested that acidification causes conformational changes in the peptide structure, thus activating the peptide-induced fusion of liposomes. The fusing capacity of the predicted Lassa virus fusion peptide is similar to that of viruses characterized by a pH dependent step at the initial stages of the viral infection. PMID- 1912066 TI - [Second messengers in heart cells and smooth muscle vessels]. AB - Advances in regulation by secondary messengers of Ca2+ level in cardiomyocyte and vascular smooth muscle cell cytosols with special reference to the major differences in regulatory effects in cells of the both types are reviewed. The effects of cAMP, cGMP, Ca2+, calmodulin, diacylglycerol and polyphosphoinositides on the Ca(2+)-channel, Ca(2+)-ATPase, plasmalemma, sarcoplasmic reticulum and outer membrane Na+/Ca2+ uniporter function are considered. Compartmentation of secondary messengers and protein kinase in cardiac and vascular smooth muscle cells should be taken into consideration during extrapolation of in vitro data to an in situ situation. The feasible role of impaired phosphorylation of membrane bound proteins of cardiac and vascular smooth muscle cells in cardiac insufficiency and atherosclerosis is discussed. PMID- 1912067 TI - [Interaction of isoforms of subfragment-1 of myosin, containing fluorescently labelled alkaline light chains, with muscle fiber actin]. AB - Using polarization microfluorimetry, the interaction of myosin subfragment 1 (S1) isoforms containing alkali light chains A1 and A2 respectively (S1(A1) and S1(A2] with F-actin of single glycerinated rabbit skeletal muscle fibers was studied. The alkali light chains of S1 were substituted by reassociation for A1 or A2 chains modified by a fluorescent label (1.5-IAEDANS) at the single SH-group located in the C-terminus. It was found that in S1(A1) bound to muscle fiber F actin the mobility of the fluorescent label is lower than in S1(A2). At the same time the S1(A1) and S1(A2) interaction with F-actin induces similar changes in polarized fluorescence of rhodamine linked to falloidine which, in turn, is specifically bound to F-actin. It is concluded that the both S1 isoforms bind to F-actin and produce similar effects on the conformational state of actin filaments in muscle fibers. Local differences between S1(A1) and S1(A2) seem to be due to the interaction of the N-terminus of A1 within S1(A1) with the C terminal region of actin. PMID- 1912068 TI - [Regulation of supermolecular organization and catalytic activity of the lysosomal complex GM1-galactosidase and neuraminidase in vitro]. AB - The regulation of the catalytic activity and supramolecular organization of human kidney Gm1-galactosidase and neuraminidase was investigated in the reversed micellar systems of Aerosol OT in octane. It was found that in the reversed micellar systems the Gm1-galactosidase can exist in the monomeric, tetrameric or octameric forms depending on the H2O/surfactant ratio in the system which determines the micelle size. The association of Gm1-galactosidase monomers into octameric structure characteristic of Gm1-galactosidase in the lysosomes results in a two fold increase of the specific catalytic activity of the enzyme. 32 kDa "protective" protein--the component of Gm1-galactosidase--neuraminidase native complex was found to improve significantly this association. PMID- 1912069 TI - [Phosphorylation and other properties of proteins binding single-stranded DNA (SSB-proteins) from chromatin and extrachromatin fractions of Ehrlich ascites carcinoma]. AB - A comparative study of single-stranded DNA-binding proteins (SSB-proteins) isolated from chromatin and the extrachromatin fraction of Ehrlich ascites tumour cells was carried out. No differences were found either in SDS-gel electrophoretic mobility or in the single-stranded DNA-binding capacity and stimulation of the replicative synthesis of DNA. However, chromatin SSB-proteins contained 1.4-1.5 times more phosphate than extrachromatin proteins. Both preparations could be phosphorylated in vitro by protein kinase C and cAMP dependent protein kinase, but the chromatin proteins were phosphorylated in a lesser degree. In parallel with phosphorylation the SSB-proteins displayed a higher binding affinity for ssDNA-cellulose. Phosphorylation can thus be regarded as a means of regulation of the SSB-protein function, in particular, their interaction with chromatin DNA. PMID- 1912070 TI - [Superoxide dismutase in liver ischemia]. AB - The properties of Cu,Zn-superoxide dismutase (SOD) from rat liver after 2-hour total ischemia or after ischemia with subsequent 24-hour reperfusion were studied. Two hours after ischemia the specific activity of SOD decreases drastically (about 3-fold) - from 510 +/- 11 u./mg in normal tissue and 196 +/- 33 u./mg after ischemia showing a further increase after reperfusion (276 +/- 40 u./mg). Using competitive immunoenzymatic analysis, the relative contents of SOD in the cytosol were determined. After ischemia the SOD content in the cytosolic fraction decreased (approximately 3-fold) but returned to the initial level after reperfusion. Polyacrylamide gel electrophoresis revealed that in control samples active SOD is heterogeneous and produces 3-4 bands, similar to the purified SOD from rat liver. After the ischemia the intensity of minor fast band IV increased and a new band V of a still higher mobility appeared. After the reperfusion the electrophoretic patterns were similar to control. Two or three times more SOD antigen from ischemia liver cytosol was absorbed to the surface of polystyrol plate in a direct sorption enzyme immunoassay procedure as compared to that from intact liver cytosol. It is suggested that the decreases of amount and the activity as well as changes of properties of SOD could be due to its oxidative modification and degradation of the modified enzyme. PMID- 1912071 TI - [Regularities in androgen reception in rat liver and its role in realizing direct androgenous effects]. AB - The content of androgen receptors (AR) in the cytosol and nuclear fractions of rat liver cells was studied by using the radioligand method. It was found that the nuclear AR content depends on the sex of animals as well as on the initial level of AR in the cytosol fraction. Elevation of AR concentration (p less than 0.05) in liver nuclei of different groups of animals was noted one hour after injection of 100 micrograms of methyltrienolone (R-1881). This elevation correlated positively with the initial level of AR in the cytosol. The accumulation of AR in liver nuclei was more pronounced in intact males than in females. A direct positive correlation between the initial level of cytosol AR and the final regulatory effect of androgens on the hepatic AR content (r = 0.955, n = 6, p less than 0.02) and on the content of the hepatic unusual estrogen-binding protein (UEBP) (r = 0.957, n = 9, p less than 0.001) were found. It is concluded that androgens induce in liver nuclei the accumulation of AR whose level correlates with that of the initial cytosolic AR. The latter reflects the efficiency of the direct effect of androgens on liver cells. PMID- 1912072 TI - [Regulation of cooperative properties of alpha-ketoglutarate dehydrogenase by means of thiol-disulfide metabolism]. AB - The redox state of two SH-groups per enzyme subunit has been shown to control the cooperative properties of alpha-ketoglutarate dehydrogenase. These thiols oxidized, alpha-ketoglutarate dehydrogenase does not exhibit any cooperative properties. The enzyme reduction leads to subunit interactions. It has been found that the most effective agent reducing the alpha-ketoglutarate dehydrogenase thiols essential for the cooperativity is dihydrolipoate, one of the intermediates of the overall alpha-ketoglutarate dehydrogenase reaction. The possibility of changing the properties of alpha-ketoglutarate dehydrogenase in the multienzyme complex under the conditions when the lipoic acid integrated into the complex is reduced, has been investigated. Thus, incubation of the alpha ketoglutarate dehydrogenase complex with NADH has been found to induce the conversion from the non-cooperative form to the cooperative one, presumably through the reduction of lipoic acid bound to the complex in the reaction catalyzed by lipoyl dehydrogenase, the third component of the complex. PMID- 1912073 TI - [Induction of cytochrome P-450 by triterpensaponins in Vietnamese ginseng]. AB - It was found that rat liver cytochrome P-450 is induced by the Vietnamese ginseng triterpensaponines mixture (TSM) as well as by K5VN Panaxozides-11 (VP-11) purified from this mixture. Addition of TSM and VP-11 accelerates benz(alpha)pyrene and aminopyrine hydroxylation and increases the content of cytochrome P-450 isoforms with Mr of 57 kDa and 54 kDa in rat liver microsomes. Since VP-11 accounts for about 50% of TSM, the results obtained suggest that the microsomal monooxygenase system induction is caused by this triterpensaponine. Induction by TSM and VP-11 was compared to that by phenobarbital (PB) and 3 methylcholanthrene (MC). It was shown that according to their inductive action TSM and VP-11 belong neither to the PB- nor to the MC-type. Cytochrome P-450 induction may play an important role in the triterpensaponine action on the organism, because this enzyme participates in the metabolism of such endogenous compounds as prostaglandins, steroid hormones, cholesterol, etc. PMID- 1912074 TI - [The effect of perfluordecaline on the activity of phase III xenobiotic transformation enzymes]. AB - Injection of perfluorodecaline to rats caused an increase of the phase II xenobiotic biotransformation enzyme activities followed by cytochrome P-450 induction. The activities of liver microsomal UDP-glucuronosyl transferase and glutathione transferase increased by 130 and 40%, respectively, against the control level. The increase of the cytosolic glutathione transferase activity was insignificant In contrast, the activity of sulfotransferase decreased about 2 fold. The role of modification of xenobiotic biotransformation enzymes in the biological effect of perfluorodecaline is discussed. PMID- 1912075 TI - [Certain biochemical characteristics of an insulin-like substance from the bivalve mollusk Anodonta cygnea]. AB - An insulin-like substance (ILS) was isolated from the visceral organs of the bivalve mollusc Anodonta cygnea by chromatography on a sulfocationite CU-23 and purified by reverse phase liquid chromatography. ILS was shown to be made up to several fractions with Mr ranging from 9 to 20 kDa which have identical amino acid composition but different hydrophobicity and N-terminal amino acids. It was supposed that the heterogeneity of ILS fractions is due to its genetical or posttranslational polymorphism. ILS has a low (0.02%) affinity for the mammalian insulin receptor and a low immune affinity for mammalian insulin and possesses a mitogenic activity which is commensurate with that of the epidermal growth factor. The data obtained suggest that Anodonta cygnea ILS represents a separate branch of a relatively ancient family of insulin-like hormones and growth factors responsible for metabolism and proliferation of invertebrate tissues. PMID- 1912076 TI - [Study of the dependence of the permeability of phosphatidylcholine liposomes for glucose on their prostaglandin level]. AB - It was found that incorporation into phosphatidylcholine monolamellar liposomes of prostaglandin E1 or its synthetic analog containing a phenol group instead of a carboxyl one leads to a significant decrease of the liposome permeability for glucose. The prostaglandin E1 analog appeared to be more membrane-active one. The data obtained were compared with the experimentally established changes in the monolayer compressibility. The experimental results are discussed in terms of a theoretical model which entails that this permeability is proportional to the number of dynamic whose diameter markedly exceeds the molecular size of glucose. PMID- 1912077 TI - [The effect of various low molecular weight compounds on the cation-binding properties of troponin with the heart]. AB - Using models of various complexity (isolated troponin C, troponin C-troponin I complex, troponin complex, troponin-tropomyosin complex, myofibrils), the effects of several low molecular weight organic compounds on the Ca(2+)-binding properties of troponin C were investigated. Trifluoperazine, calmidazolium and substance 48/90 increased the affinity of Ca(2+)-specific sites of troponin C both in the case of isolated troponin and in all the complexes under study. Nicardipine had no effect on the cation-binding activity of isolated troponin C, but increased the affinity of the Ca(2+)-binding sites of troponin C in the complex with troponin I. The cardiotonic drugs APP 201-533 and DPI 201-106 had practically no effect on the cation-binding properties of isolated troponin C or of simple complexes of troponin C. At the same time APP 201-533 increased, whereas DPI, 201-106 decreased the affinity of the Ca(2+)-binding sites of troponin C in myofibrils. It is concluded that the effects of the drugs on the cation-binding properties of troponin C depend on the protein-protein interaction with the filament. Studies of physiological activity of low molecular weight organic compounds require a detailed analysis of their effects on the Ca(2+) binding activity of troponin C included into protein complexes of different complexity. PMID- 1912078 TI - Enhancement of histological detail using metanil yellow as counterstain in periodic acid Schiff's hematoxylin staining of glycol methacrylate tissue sections. AB - Histological detail in sections from tissues embedded in glycol methacrylate was improved by counterstaining PAS/iron-hematoxylin stained sections with a dilute solution of metanil yellow. The addition of the counterstain increases contrast in tissue sections and highlights PAS-positive entities. The staining protocol provides sharp definition of tissue morphology, differentiates cell types and other tissue components and does not produce background staining. PMID- 1912079 TI - Enzyme, lectin and immunohistochemistry of plastic embedded undecalcified bone and other hard tissues for light microscopic investigations. AB - Enzymes and tissue antigens were localized on plastic embedded undecalcified bones and teeth using Technovit 7200 VLC (Kulzer, Germany). This resin is hard enough for cutting and grinding procedures on rotating plates with diamond layers. The pores between the diamond grains are not obstructed with this resin. The procedure described here permits localization of antigens in the soft tissues adjacent to, or in the biological hard tissues themselves and in dental implants (ceramic or metallic) on the light microscopic level. The undecalcified bone is fixed and embedded in plastic and cut at 100-150 microns. The slices are ground automatically by a grinding machine to a thickness of 5-10 microns. After application of the substrates for alkaline and acid phosphatases and the required dyes, the distribution of these enzymes can be demonstrated. Tissue antigens also can be detected with slightly modified standard techniques of immunohistochemistry and lectin histochemistry using the peroxidase technique or fluorescence microscopy. PMID- 1912080 TI - The taming of immunohistochemistry: the new era of quality control. AB - The most critical factor for interpreting the results of immunohistochemistry is verification of antibody sensitivity and specificity. While some manufacturers supply material data sheets with this information, many do not. This paper describes a well-defined quality assurance program for testing immune reagents. This program can be used to provide commercial suppliers of antisera with analyses of their products destined for government licensure applications. This paper illustrates the protocol and explains the testing philosophy developed over the last eight years. PMID- 1912081 TI - A new technique facilitating studies of scant cell specimens. AB - A simple method is described by which multiple cytological and cytochemical studies can be done on a clinical sample that contains relatively few cells. The cells are concentrated by centrifugation. The cell pellet is fixed, frozen and embedded in plastic. Thin (2-microns) sections are cut from the plastic. Thus, each cell may appear in several sections and many slides can be made from a single specimen. The advantages of this method over cytospins and Millipore filter preparations of cell suspensions are optimal utilization of all cells, excellent morphological and immunological preservation and ease and reproducibility of this technique. PMID- 1912082 TI - Crush and smear technique for rapid detection and semiquantitation of amyloid deposition. AB - A method using Congo red to rapidly identify and semiquantitate amyloid deposits in tissues for experimental research and clinical medicine is described. Examination by polarization microscopy revealed amyloid deposits as bright green birefringent clumps on a dark red background. On semiquantitative evaluation, good correlation was found between this technique and the conventional histological one, the present technique being more sensitive. The method described saves time and expense. PMID- 1912083 TI - In situ hybridization of Lilium whole mount synaptonemal complex chromosomal preparations. AB - Whole mount meiotic preparations of the synaptonemal complex complement of Lilium have been used for in situ hybridization experiments. A probe of the maize ribosomal DNA gene cluster has been successfully hybridized to the lily preparations. Three strong signals, corresponding to the three known lily nucleolus organizer regions, have been seen in most of the chromosome preparations. In situ hybridization experiments using meiotic preparations should be useful for identifying specific chromosomes, and for investigating the role of particular DNA molecules important to meiotic function. PMID- 1912084 TI - Test systems with synthetic peptide substrates in haemostaseology. AB - Since the early seventies, synthetic peptide substrates have been used in haemostaseology, enabling the introduction of photometry in coagulation analysis. Synthetic peptide substrates are short peptides (3-5 amino acid residues), with a chromogenic group coupled to the C-terminal end by an amide bond. The chromogenic group may be relatively specifically removed by proteases, and measured photometrically. By using the special properties of the many available substrates, test systems have been developed for procoagulant clotting factors, fibrinolytic factors, inhibitors of both systems and also for global tests of plasmatic coagulation. These tests can be performed manually or on automated analytical systems with high specificity, sensitivity and accuracy. The analytical advantages and new possibilities of the tests with chromogenic substrates have, in recent years, decisively stimulated not only haemostaseological basic research, but also clinical investigation and routine. Today, inhibitors of plasma coagulation (e.g. antithrombin III, protein C, C1 esterase inhibitor) as well as fibrinolytic parameters (e.g. tissue plasminogen activator, plasminogen activator inhibitor, alpha 2-antiplasmin) are nearly exclusively determined with chromogenic substrates. Further development will constitute the application of chromogenic substrates to "dry chemistry" methods. PMID- 1912085 TI - Plasma concentration of coagulation and fibrinolysis factors and platelet function in hypertension. AB - Fifty-one patients with mild hypertension were evaluated in relation to the plasma concentrations of coagulation and fibrinolysis factors as well as for the aggregability of their platelets. In a considerable number of the patients (18/51), a significantly enhanced in vitro ADP (2 mumol/l)-induced aggregation was found. In the coagulation line significant increases could be demonstrated in fibrinogen, fibrin monomers and thrombin-antithrombin III. The fibrinolysis system showed significant increases for D-dimers, tissue plasminogen activator antigen and plasminogen activator inhibitor, whereas the tissue plasminogen activator activity was significantly diminished. Remarkably, there seems to be a discrepancy between the (low) tissue plasminogen activator activity and the (higher) plasminogen activator antigen concentration. Alterations in the plasma concentrations of the investigated coagulation and fibrinolysis factors and in the aggregability of the platelets are indicative of an involvement of coagulation, fibrinolysis and platelets in hypertension, which can be considered as partial risk factors for thrombophilia. PMID- 1912086 TI - Quantitative determination of non-haem iron and ferritin iron in bone marrow using flameless atomic absorption spectrophotometry. A comparative study on the cytological and chemical determination of the bone marrow iron content. AB - A method for non-haem iron analysis in bone marrow aspirates using graphite furnace atomic absorption spectrophotometry has been developed. Bone marrow aspirates were obtained from patients with various disorders. A good correlation is observed between chemical and cytological assessment of total non-haem iron in bone marrow. An intra-assay coefficient of variation of 9.0% was observed. The ferritin-iron concentration was also determined and a CVduplo of 11% was found. The ferritin iron concentration increased with an increasing total iron content until saturation of ferritin appeared to be reached at about 3 g ferritin per kg protein. It was concluded that the quantitative determination of bone marrow iron can be of value in the diagnosis and investigation of both hypo- and hyper ferraemic disorders. PMID- 1912087 TI - Determination of pyrimidine deoxynucleoside triphosphates in leukaemia cell extracts containing 1-beta-D-arabinofuranosylcytosine triphosphate. AB - Deoxynucleoside 5'-triphosphates (dNTPs) can be determined in cell extracts by high performance liquid chromatography after prior selective degradation of ribonucleoside 5'-triphosphates with sodium periodate and methylamine. When the method is used for the evaluation of deoxynucleoside triphosphates in 1-beta-D arabinofuranosylcytosine triphosphate (ara-CTP)-containing cell extracts, an additional peak coeluting with thymidine triphosphate (dTTP) is observed. This peak is due to the formation of a carboxylic acid derivative of ara-CTP by periodate oxidation, and it can lead to considerable overestimation of dTTP. Formation of this peak can be avoided by using alkaline reaction conditions (pH 7.5) and by changing the sequence of addition of the reagents used in the periodation procedure. By employing this modified protocol, cellular dNTP and ara CTP levels can be monitored in extracts of leukaemic blasts during cytosine arabinoside treatment in two separate HPLC runs. PMID- 1912088 TI - The route of prolonged morphine administration affects the pattern of its metabolites in the urine of chronically treated patients. AB - Differences in the patterns of urinary morphine metabolites were determined in 15 patients after the prolonged administration of morphine via various routes (oral, subcutaneous, intravenous). The possible correlation between metabolite pattern and the route of prolonged morphine administration was investigated. It was established that the concentration ratios of the active metabolite, morphine-6 glucuronide to morphine and its inactive metabolite, morphine-3-glucuronide are significantly (p less than 0.05) higher after prolonged oral morphine treatment than after the systemic administration (subcutaneous or intravenous infusion) of morphine. It may therefore be concluded that patients receiving morphine orally produced significantly greater amounts of its pharmacologically more active metabolite than patients subjected to chronic systemic morphine treatment. PMID- 1912089 TI - Rapid diagnosis of familial defective apolipoprotein B-100. AB - A method is described for the rapid, economic and non-radioactive examination of DNA samples from hypercholesterolaemic patients for familial defective apolipoprotein B-100, using a modified polymerase chain reaction (PCR) protocol and restriction enzyme isoform genotyping. Because of the high prevalence of familial defective apolipoprotein B-100, which is estimated to be one in 500 in most screened general populations, interest is focussed on a simple method for detection of this point mutation. In our protocol a diagnostic restriction site is created by PCR, using a specifically designed partly mismatched primer. In the case of familial defective apolipoprotein B-100 the amplified DNA segment contains an additional ScaI site, whereas DNA amplified from the normal allele is resistant to ScaI digestion. A rapid differentiation between the two alleles is achieved by agarose gel electrophoresis of the ScaI-digested PCR product. PMID- 1912090 TI - Measurement of beta 2-microglobulin in serum by a particle-enhanced nephelometric immunoassay. AB - A particle-enhanced immunoassay of beta 2-microglobulin in serum is described. It is based on the agglutination of complexes formed between the serum beta 2 microglobulin and latex particles coated with F(ab')2 fragments of polyclonal anti-beta 2-microglobulin antibodies. The analytical range of the method is 0.50 to 16 mg/l; it can be extended by appropriate dilution to 0.12 to 80 mg/l with good precision (CV less than 5% over the whole range). The accuracy and the precision are confirmed by a good correlation with radioimmunoassay (n = 123, r = 0.993). No error due to antigen excess was observed, even up to 292 mg/l. The main advantages of the method are its simplicity, its low cost per test and its high sensitivity (final dilution of the sample at 1/1200) with no known interference. The calibration curve is stable for at least 2 weeks. PMID- 1912091 TI - Highly sensitive immuno-assays for the determination of cotinine in serum and saliva. Comparison between RIA and an avidin-biotin ELISA. AB - Two immuno-assay methods (RIA and ELISA) have been developed for the accurate and sensitive measurement of cotinine in human body fluids (serum, saliva). RIA uses [3H]cotinine as antigen and charcoal/dextran for separating cotinine-bound antibodies from the free derivative. Another technique (ELISA) was developed to avoid the use of radio-labelled compounds and to determine cotinine in large populations, including passive or non-smokers who usually present very low concentrations. The two techniques were analytically validated. The detection limit was similar (0.1 micrograms/l) and the precision was better than 10% for both techniques. Non-smoker values ranged from 0.1 to 17 micrograms/l by ELISA and 0.1 to 27.5 micrograms/l by RIA, whereas smoker values ranged from 50 to 1000 micrograms/l (ELISA) and from 70 to 800 micrograms/l (RIA). The comparative analysis of cotinine in 96 human sera revealed a good correlation between the two methods (r = 0.97) and a reliable discrimination between the populations of non smokers and smokers. As usual, the ELISA is more rapid (4 h 30 min) than the RIA (longer than 48 h). ELISA is proposed for use in the epidemiological investigation of the human tobacco risk. PMID- 1912092 TI - Cholesterol determinations from skin puncture and venous blood have similar imprecisions. AB - Comparison of cholesterol values from venous blood and skin puncture blood is difficult, because biological differences between both materials may be concealed or increased by the preanalytical imprecision of skin puncture. In 12 adults, we studied the variance of cholesterol and urea determination in 8 blood samples obtained by the puncture of 8 fingers and compared the results with the 8-fold determination of a venous sample drawn simultaneously. Our results show that the additional imprecision of skin puncture is low, and that the differences are not statistically significant. The mean values for cholesterol were 3.9% lower in skin puncture plasma than in venous plasma, whereas the mean values for urea were very similar. PMID- 1912093 TI - Metrological terminology instead of analytical terminology. PMID- 1912094 TI - Regulation of ketone formation and phosphoenolpyruvate carboxykinase activity in the small intestinal mucosa of infant rats. AB - We studied the effect of different hormones added in vivo or in vitro on ketogenesis and phosphoenolpyruvate carboxykinase (PEPCK) activity in the small intestinal mucosa of suckling rats. Injection of insulin or dexamethasone in vivo or of an antiglucagon antiserum decreased the rate of ketone formation in the mucosa whereas injection of anti-insulin antiserum led to increased mucosal ketogenesis. PEPCK activity in the mucosa was decreased by the antiglucagon serum but was not affected by insulin or anti-insulin serum injections. Both liver and brown fat PEPCK responded as expected with the activity being elevated by anti insulin serum and depressed by both insulin and antiglucagon serum. In the in vitro experiments, no effect of any of the agents on PEPCK was found. Ketone formation was suppressed in vitro by insulin or dexamethasone addition to the medium. PMID- 1912095 TI - Growth hormone regulation by growth hormone-releasing hormone in infant rhesus monkeys. AB - To study the relationship of endogenous GHRH to the changes seen in serum GH concentration in neonatal primates, we administered antiserum to GHRH (GHRH-Ab) or GHRH antagonist, (N-Acetyl-Tyr1,D-Arg2)GHRH-(1-29)-NH2, to unanesthetized, fasted rhesus monkeys, 1-31 days of age, via an acutely placed venous catheter. The administration of GHRH-Ab resulted in a significant decrease in serum GH concentration at 1-2 and 7-9 days, but not at 28-31 days of age. The administration of GHRH antagonist resulted in a significant decrease in serum GH concentrations at 1-2 days, but not at 7 or 14 days of age. These results imply that basal serum GH is more dependent on endogenous GHRH at 1-2 days than after 7 28 days of age. This suggests developmental changes in the hypothalamic regulation of GH secretion with advancing age in the neonatal period. PMID- 1912096 TI - Carcass and tissue fat content in the pregnant rat. AB - The present study in rats was aimed at determining the specific day of pregnancy on which maternal body fat accumulation starts and which tissues are involved. Most of the body weight increase at day 12 of gestation corresponded to conceptus free maternal weight which progressively increased until the 19th day of gestation after which maternal weight stabilized and the rate of conceptus weight gain became maximal. Maternal carcass fat content progressively increased until day 18 of gestation, increased very markedly on day 19, stabilized between day 19 and 20 and then decreased on day 21. These changes were the opposite of the course of the specific-gravity values. The fresh weight of lumbar fat-pads and mesenteric adipose tissue reflected the changes in carcass fat content throughout gestation. Periuterine adipose-tissue mass declined on day 12 of gestation to be recuperated later, subcutaneous adipose tissue increased on day 12 to decline progressively thereafter and interscapular brown adipose tissue remained stable until day 20 and increased on day 21. With only a few exceptions, the lipid concentration in all these adipose tissues remained stable throughout gestation. Mammary glands and liver weights increased intensely from day 12 and, whereas the lipid concentration in the former was stable, in the latter it decreased on day 12 and increased on days 18 and 19. These results show that in the rat (a) maternal carcass fat accumulation during gestation is not paralleled by the size of the different fat-storing tissues and (b) mammary-gland fat accumulation also contributes to maternal fat storage. PMID- 1912097 TI - Sn-protoporphyrin plus photoirradiation induces lipid peroxidation in vivo and in vitro in nonjaundiced Gunn rats. AB - Lipid peroxidation induced by Sn-protoporphyrin (SnPP) plus photoirradiation was investigated in vivo and in vitro using nonjaundiced Gunn rats. Membrane lipids from young adult rat brain were peroxidized by SnPP plus photoirradiation depending on the SnPP concentration and photoirradiance. Similarly, coadministration of SnPP and photoirradiation to suckling rats increased lipid peroxides in the whole blood and was found lethal. The influence of the wavelength distribution of light sources was also examined by using blue-white and green fluorescent lights. The photodynamic effect by green light irradiation whose energy distribution had no overlap with the Soret band of SnPP was about half of that produced by blue-white light with regard to the membrane peroxidation and the lethal effect on neonatal rats. We therefore conclude that the combination of SnPP and photoirradiation is a potentially hazardous treatment of neonatal jaundice. PMID- 1912098 TI - Reduced levels of galactose-terminated glycoproteins in rat serum during perinatal development. AB - Asialoglycoprotein receptor is an abundant protein localized in the sinusoidal domain of the hepatocyte plasma membrane. Its principle function is the clearance of serum glycoproteins which include several acute phase reactant proteins that have lost their terminal sialic acid residue. It has been reported that asialoglycoprotein receptor is nearly absent in mammalian fetal liver but rises to adult levels during the early postpartum period. The hypothesis to be tested was to determine whether defective glycoproteins, those lacking terminal sialic acid residues, are accumulated in fetal serum as a result of reduced receptor content. It was found that low levels of asialoglycoprotein receptor in 18-day old fetal liver correlated to a threefold higher level of total asialoglycoproteins in fetal serum than adult serum as determined by a modified Western blot protocol employing radioiodinated ricinus communis agglutinin, a galactose-binding lectin. As hepatic asialoglycoprotein receptor accumulated at the time of birth, the elevated level of serum asialoglycoproteins decreased to adult values in an opposite manner. This study indicates that the hepatic asialoglycoprotein receptor plays an important role in reducing the amount of circulating defective glycoproteins at the time of birth. PMID- 1912099 TI - Metallothionein messenger RNA levels in the macular mutant mouse: an animal model of Menkes' kinky-hair disease. AB - Levels of metallothionein-1 (MT-1) messenger RNA (mRNA) in various tissues from normal and macular mutant mice at different stages of development (17 days of gestation, 1-, 3-, 7- and 14-day-old) were determined by Northern blot analysis. Renal MT-1 mRNA levels in mutant mice were slightly elevated at 3 stages compared to normal mice, with the exception of mutant fetus and 3-day-old mutant mice. Intestinal MT-1 mRNA levels in mutant mice were elevated at 3 stages compared to normal mice with the exception of mutant fetus and 3-day-old mutant mice. Hepatic MT-1 mRNA levels in mutant fetus and 1-day-old mutant mice were approximately the same compared to normal mice. In 3- and 7-day-old mutant mice, hepatic MT-1 mRNA levels were depressed and in 14-day-old mutant mice, they were increased compared to normal mice. Brain MT-1 mRNA could not be detected in normal and mutant mice at the 4 stages with the exception of 14-day-old mice. MT-1 mRNA in 14-day-old mice was detected and the level of that in mutant mice was slightly elevated compared to normal mice. After injection of Cu, MT-1 mRNA levels in kidney, liver and intestine were determined. The injection of Cu increased the level of MT-1 mRNA in the tissues of normal and mutant mice compared to control (saline injected) mice. Significant differences in MT-1 mRNA levels in the tissues of both Cu-injected mice were not observed. PMID- 1912100 TI - Febrile convulsions induced by microwaves and the alteration in behavior of albino mouse OF1. AB - We studied the effects of microwave (2,440 MHz) induced febrile convulsions (FCs) on the behavior and development of 31 albino mice (OF1 strain), between 25 and 30 days old, in comparison with a group of 33 animals from the same litters. Previously a string test was adapted to measure the neurodevelopment of mice in the first 6 months of life with 82 animals of the same characteristics. The animals submitted to convulsions (fit temperature = 39.2 +/- 0.96 degrees C) showed normal growth, in fact they obtained better results in the test than the control mice (2-way ANOVA, p less than 0.01). FCs have no negative influence on the normal behavior of the mouse. PMID- 1912101 TI - Insulin-like growth factor I and II gene expression in Balb/C mouse liver during postnatal development. AB - We studied the developmental shift from IGF-II to IGF-I mRNA synthesis in Balb/C mouse liver. IGF-I mRNA levels were low at birth, increased with age to peak at weaning, and IGF-I gene expression again increased during puberty. IGF-II expression was high during early postnatal development, but became nondetectable at weaning. Thus in early life there is a reciprocal relationship of rising IGF-I and falling IGF-II mRNA. Northern analysis revealed four IGF-I mRNA transcripts ranging from 1.1-7.0 kb, with the 1.1 kb being the most prominent. Five IGF-II transcripts ranging from 1.7-4.0 kb were found, with the 4.0 kb being the most prominent. The pattern of Serum IGF-I and IGF-II values paralleled liver IGF-I and IGF-II mRNA levels. PMID- 1912102 TI - Where there's smoke ... nicotine and psychiatric disorders. PMID- 1912103 TI - Effect of electroconvulsive therapy on serum concentration of alpha-1-acid glycoprotein. AB - Recent studies have shown significant alterations in serum alpha-1-acid glycoprotein (AGP) concentration in epileptic patients, the major protein to which basic drugs bind in serum. To date, there have been no reports in the literature investigating the effects of generalized seizures as a result of repeatedly administered electroconvulsive therapy (ECT) on this serum protein. As the cyclic antidepressants are basic drugs that bind avidly to AGP, an alteration of AGP concentration by ECT could represent a mechanism of interaction between two somatic treatments for depression. We therefore determined the serial AGP concentrations of 10 patients undergoing repeated ECT. AGP concentrations were determined by radial immunodiffusion on serum samples obtained at each treatment session (course of treatment ranged from 4 to 12 sessions over 8 to 32 days). The mean (SD) AGP concentrations prior to and at the end of ECT were 88.7 (18.3) mg/dl and 97.8 (24.8) mg/dl, respectively. Variability in AGP concentration was observed over the course of treatments with no consistent trend (intrapatient coefficients of variation averaged 11.5%). These data suggest that serial ECT does not produce consistent, significant changes in serum AGP concentrations and should have limited effects on altering the serum protein binding and, therefore, pharmacological effects of concurrently administered cyclic antidepressants. PMID- 1912104 TI - Platelet 5-HT2 serotonin receptor binding sites in autistic children and their first-degree relatives. AB - We examined platelet serotonin2 [5-hydroxytryptamine2 (5-HT2)] receptor binding sites, whole blood serotonin (5-HT), and plasma norepinephrine (NE) in male autistic children and their first-degree relatives. Saturation studies utilizing 125I-spiroperidol labeled the 5-HT2 sites with an affinity of 224.6 +/- 84.4 pmol/L (Kd). No group differences, i.e., autistic (n = 12), siblings (n = 6), parents (n = 22), control (adult; n = 7: child; n = 10), were seen for either the Kd or the total number of sites (Bmax: 14.3 +/- 10.9 fmol/mg protein). No correlations were found in any group between binding parameters (Kd or Bmax) and whole blood 5-HT. For the parental group, inverse correlations were found between NE and Bmax (standing NE, rs = -0.67, n = 21, p = 0.001; supine NE, rs = -0.49, n = 22, p = 0.021). In the autistic group, no correlation was seen between plasma NE and Bmax. A correlation between the autistic boys' Bmax and their fathers' Bmax was observed (rs = 0.79, n = 11, p = 0.004). These findings suggest (1) circulating NE may be involved in heterologous regulation of 5-HT2 receptors in the platelet and (2) genetic (paternal-filial) factors may play a role in the expression of 5-HT2 binding sites in the platelet. These preliminary findings are discussed in relation to heterologous receptor regulation. The relationships between these findings and either the pathophysiology of autism or hyperserotonemia in autism are unknown. PMID- 1912105 TI - A pilot placebo-controlled study of chronic m-CPP administration in Alzheimer's disease. AB - Meta-Chlorophenylpiperazine (m-CPP), a serotonin agonist and metabolite of the anti-depressant trazodone, was administered chronically to eight moderate to severely affected Alzheimer patients to determine whether it would produce improvement in behavioral symptoms complicating this illness. In doses up to 80 mg/day for 16 days, m-CPP was well tolerated and resulted in small but significant increases in anergy and depression-related symptoms compared with placebo. The effects of chronic m-CPP in this study contrast with the reported beneficial effects of the parent compound trazodone and selective 5-HT reuptake inhibitors in treating behavioral symptoms in Alzheimer patients. PMID- 1912106 TI - Plasma phenylethylamine in schizophrenic patients. AB - Plasma samples were collected from 41 patients who met DSM-III criteria for schizophrenia and from 34 healthy controls. Phenylethylamine (PE) levels were determined using a gas chromatography-mass spectrometry negative chemical ionization method. PE was significantly higher in the schizophrenic patients compared with controls. There were no differences in PE between paranoid and nonparanoid patients. Plasma PE did not appear to be influenced by the severity of schizophrenic symptoms (rated by BPRS, SANS, and SAPS) or by the amount of dietary phenylalanine ingested within 24 hr of testing. Plasma PE did not correlate with current or past exposure to neuroleptic medication. It was not possible, however, to test individual patients during two periods when they were taking and not taking medication. Thus it is possible that neuroleptic exposure may have confounded the results. This study provides further evidence that PE excess may play a role in the etiology of schizophrenia but does not support previous studies which suggest that such an abnormality is limited to the paranoid subgroup. PMID- 1912107 TI - Dose dependent inhibition of REM sleep in normal volunteers by biperiden, a muscarinic antagonist. AB - We tested the effect of biperiden (2, 4, and 8 mg per os 30 min before bedtime) on the polygraphically recorded sleep of normal volunteers (n = 8). Biperiden is a cholinergic, muscarinic receptor antagonist that may preferentially block the M1 receptor subtype. Compared with placebo, biperiden significantly prolonged rapid eye movement (REM) latency and suppressed REM sleep time and REM percentage in a dose-dependent manner. These REM suppressing effects of biperiden are similar to those previously reported with scopolamine and other nonselective muscarinic receptor antagonists. Because of uncertainties about the pharmacological specificity of biperiden, further studies are needed to determine the mechanism of action and the role of M1 receptors subtypes in the regulation of REM sleep. PMID- 1912108 TI - Endogenous event-related brain potentials and psychometric performance in children at risk for schizophrenia. AB - Two independent groups of high-risk children for schizophrenia and their matched control children were submitted to the following experiments: an auditory oddball paradigm registrating late event-related potentials (ERPs) and a psychometric test battery including the assessment of Wechsler Intelligence Scales, reaction times (after regular and irregular preparatory intervals), and the d2-attention test. The study was intended to clarify whether long-latency ERPs and the selected psychometric tests would contribute to reliably differentiating between these groups. The results showed significantly prolonged latencies of the P3 component of the ERPs to rare, task-relevant target stimuli in both high-risk groups compared with the controls. Similarly, the N2 latencies were delayed in both groups. By contrast, ERP patterns to frequent, nontask-relevant stimuli were very similar, with no significant differences between high-risks and normals; nor did any ERP amplitudes show significant differences. The data are interpreted as a reflection of a subtle deficit in maintaining attention and a subsequent impairment of stimulus discrimination in high-risk children. This is consistent with the psychometric findings of higher error scores in target counts and d2 test, and significantly prolonged reaction times after regular preparatory intervals (PIs) in the high-risks. The findings may hint at a vulnerability for schizophrenia in high-risk children. Given the high prevalence of the attentional dysfunctions in both high-risk groups, however, it is hypothesized their presence does not necessarily imply an unequivocal manifestation of schizophrenia. PMID- 1912109 TI - Fluoxetine-induced suicidality, serotonin, and seasonality. AB - In spite of the complexities involved in suicide, fluoxetine has been prematurely and simplistically blamed for inducing this phenomenon. A variety of variables must be factored into such an interpretation. Nevertheless, given the complicated psychobiological circumstances involved, acute and rapid changes in serotonin (5 HT) function appear to be important to the understanding of changes in suicidal behavior. Such a mechanism may also explain the robust seasonal peak of suicides in spring. PMID- 1912110 TI - Clinical outcome and psychoendocrinological findings in a case of lethal catatonia. PMID- 1912111 TI - Sleep onset REM periods in schizophrenic patients. PMID- 1912112 TI - Nuclear magnetic resonance spectrometry in mood disorder: a preliminary report. PMID- 1912113 TI - Is investment in molecular genetics worthwhile? PMID- 1912114 TI - Pineal and adrenal function before and after refeeding in anorexia nervosa. AB - Nine female subjects with anorexia nervosa (AN) were studied when emaciated (mean 72% of average body weight), and after refeeding (mean 85% of average body weight). They were compared to 9 individually age-matched female control subjects. On each occasion blood was sampled for serum melatonin and plasma cortisol through the night, and urine was collected over 24 hr to measure sulfatoxy melatonin levels. The AN group did not differ in their level of depression before and after weight gain. There were no significant differences in serum melatonin values among the patient group before or after weight gain and the control group. Levels of urinary sulfatoxy melatonin were also significantly higher in nighttime compared to daytime samples both before and after weight gain. Plasma cortisol values were significantly elevated in the emaciated state and this was accounted for by higher cortisol levels at 9, 10, 11, and 12 PM and at 6 AM compared with the weight restored state and to controls. This study suggests that pineal activity in patients with AN is not altered by chronic changes in weight, and is not closely associated with changes in cortisol. PMID- 1912115 TI - Event-related potentials in depression: influence of task, stimulus hemifield and clinical features on P3 latency. AB - P3 latency, a brain event-related potential (ERP) correlate of stimulus evaluation time, was measured in 25 unmedicated depressed patients and 27 normal controls during auditory temporal and spatial discrimination tasks. Patients were divided into two subgroups, one having a typical major depression (melancholia or simple mood reactive depression) and one having an atypical depression. Typical depressives had abnormally long P3 latency for the spatial task but not the temporal task. They also showed an abnormal lateral asymmetry, with longer P3 latency for stimuli in the right hemifield than the left. In contrast, atypical depressives did not differ from normals in either respect. Longer P3 latency correlated with ratings of insomnia, while abnormal lateral asymmetry correlated with reduced right visual field advantage for syllables. The P3 latency findings point to a task-related slowing of perceptual decisions in a subgroup of depression. PMID- 1912116 TI - Higher postdexamethasone serum cortisol levels in agoraphobic than in nonagoraphobic panic disorder patients. AB - The dexamethasone suppression test (DST) was performed in panic disorder (PD) patients with (n = 32) or without (n = 31) agoraphobia and in normal controls (n = 49). Postdexamethasone serum cortisol levels were significantly higher in agoraphobic PD patients (105.3 +/- 19.3 nmol/L) both when compared to PD patients without agoraphobia (47.3 +/- 7.7 nmol/L; p less than 0.01) and when compared to healthy controls (51.7 +/- 8.3 nmol/L; p less than 0.01). The rate of nonsuppressors (i.e., subjects displaying postdexamethasone cortisol levels greater than 138 nmol/L) was 28% and 3% in agoraphobic and nonagoraphobic PD patients, respectively, and 12% in controls. In patients, the postdexamethasone cortisol levels did not correlate with the number of panic attacks per week, baseline anxiety as measured using the Hamilton Anxiety Scale, depressive symptoms as measured using the Montgomery-Asberg Depression scale, or duration of illness. Data from eight patients in whom a second DST was performed after treatment with imipramine or clomipramine for three months indicate that a marked reduction of the number of anxiety attacks is not necessarily accompanied by a normalization of a pathological DST. In conclusion, it is suggested that the elevated postdexamethasone cortisol levels sometimes observed in agoraphobic PD patients are more closely related to the agoraphobic behavior than to the panic attacks per se. PMID- 1912117 TI - Phototherapy in nonseasonal depression. AB - Previous reports have shown that bright light exposure may benefit patients with seasonal depression. In the present study, the possible therapeutic effect of bright light in nonseasonal major depressive disorder was examined. Forty-two depressed patients not receiving additional antidepressant medication were exposed to bright white light of 2500 lux or dim red light of 50 lux over one week for two hr daily in the morning. The change in depressive symptoms was assessed by rating scales (Hamilton Depression Rating Scale, CGI) and by self rating scales (Depression Scale, Complaint List, Visual Analogue Scale). Consistent for all ratings, the decrease in depressive symptoms after bright white light was only slight and not different from dim red-light exposure. Contrary to the findings in seasonal affective disorder, phototherapy administered over one week for two hr daily is not effective in nonseasonal major depressive disorder. PMID- 1912118 TI - Alterations of local cerebral blood flow and glucose uptake by electroconvulsive shock in rats. AB - The effects of single and repeated electroconvulsive shock (ECS) treatment on regional cerebral blood flow (rCBF) and on rates of glucose flow from blood to local brain areas (rCGF), were investigated in pentobarbital-anesthetized rats, using quantitative autoradiographic techniques. Effects of single ECS on rCBF were assessed at two average time points of 15 and 55 sec after the application of the electric current, whereas the effects on rCGF were assessed at 70 and 110 sec. Effects of repeated ECS were assessed 24 hr after the last ECS in a series of eight daily treatments. Single ECS caused marked increases in rCGF in different brain structures, but no significant effects were observed after repeated ECS. Similarly, substantial increases in rCBF were seen during and immediately after the ECS-induced seizure, but not 24 hr after the last treatment of repeated ECS. Single ECS appeared to have differential effects on rCBF in hind brain structures as compared to more anterior regions. A linear relationship between rCBF and rCGF values was established in control animals, indicating coupling of these two variables with a constant rCBF/rCGF ratio. ECS caused an apparent increase in the CBF/CGF ratio, which might be attributed to the different temporal resolution of the two methods used here to estimate rCGF and rCBF. Analysis of the increments of rCGF and rCBF extrapolated to the same point in time after a single ECS (10 sec), revealed that in many of the examined structures the CBF/CGF ratio was similar to that observed in control animals, indicating that the coupling of CBF and CGF is maintained during the seizure. But in some brain stem structures such as the dorsal raphe, inferior colliculi, superior olivary nucleus, and the vestibular nucleus there were large increases in CGF associated with a marked drop in the CBF/CGF ratio. This observation suggests that high metabolic demands can be met by increased local blood flow up to a given "ceiling" keeping the glucose clearance from blood to brain tissue constant. However, when the metabolic demands exceed this upper limit, the additional demands could be met by an increased clearance of glucose without a change in CBF. PMID- 1912119 TI - Neurocognition in acute and chronic depression: personality disorder, major depression, and schizophrenia. PMID- 1912120 TI - Serotonin-stimulated Ca2+ response is increased in the blood platelets of depressed patients. PMID- 1912121 TI - Prolactin response to the dopamine antagonist, metoclopramide, in depression. PMID- 1912122 TI - Negative symptoms of schizophrenia: the need for conceptual clarity. PMID- 1912123 TI - Left-handedness in male schizophrenic patients is associated with increased impairment on the Luria-Nebraska Neuropsychological Battery. AB - Several studies suggest increased mixed and left-handedness in schizophrenia. This is of interest as early cerebral injury can result in increased left handedness and some investigations have suggested a role for early developmental insult (e.g., birth complications) in schizophrenia. We administered the Luria Nebraska Neuropsychological Battery (LNNB) to 24 left-handed male schizophrenic patients and a separate group of 24 right-handed schizophrenic patients who were age and education matched to the left-handed patients. The test protocol also was administered to 15 left-handed non-psychiatric control subjects and 15 right handed controls. Direct comparisons (t-test) of the left- to right-handed schizophrenics revealed that the left-handed patients showed significantly greater impairment on several LNNB measures sensitive to cognitive deficits in schizophrenia. There were no differences between left- and right-handed control subjects. A further 2 X 2 ANOVA pooling all subjects noted several significant interactions between handedness and diagnostic group. The findings suggest a unique interaction between left-handedness and neuropsychological impairment in schizophrenia and could support a relationship between left-handedness, early cerebral insult, and cognitive deficits. PMID- 1912124 TI - EEG power variation in schizophrenic subgroups: effects of emotionally salient stimuli. AB - Eighteen unmedicated chronic schizophrenic patients and 13 normal controls were tested in a paradigm designed to examine functional changes in electroencephalographic (EEG) activity following presentation of emotionally salient auditory stimuli and control tones. Five standard bands of EEG spectral power were examined at bilateral frontal and temporal surface recording sites. The schizophrenic subjects were assigned to diagnostic subgroups on the basis of DSM-III-R criteria following independent clinical examination by two staff psychiatrists. Those subjects who met DSM-III-R criteria for paranoid schizophrenia were assigned to one subgroup (PS subgroup), while those who met DSM-III-R criteria for either residual or undifferentiated schizophrenia were assigned to a second subgroup (R/US subgroup). Analysis of Variance of EEG activity recorded at bilateral frontal (F1 and F2) and temporal (T3 and T4) scalp leads revealed significant diagnosis-related differences in alpha and beta-2 activity at temporal recording sites, and in beta-1 and beta-2 activity at frontal recording sites. Post-hoc tests revealed that significant differences in all four measures occurred in the R/US subgroup, which showed a decrease in temporal alpha and an increase in temporal beta-2 power as compared to controls. These variations in EEG activity appeared to demonstrate a degree of subgroup specificity, as the R/US subgroup also differed significantly from the PS subgroup on most of these measures. Significant subgroup-specific lateralization effects were also observed for temporal lobe delta activity and for frontal lobe beta-1 activity. These findings are interpreted in terms of subgroup-specific alterations in the processing of sensory information in schizophrenia, particularly when such information is emotionally salient. They suggest that subgroup differences in emotional and clinical state may be reflected in differential changes in EEG spectra within the schizophrenic population. PMID- 1912125 TI - Decreased histamine H1 receptors in the frontal cortex of brains from patients with chronic schizophrenia. AB - Involvement of histamine H1 receptor in the brains of schizophrenic patients was investigated using 3H-mepyramine as a ligand. The specific 3H-mepyramine binding in the frontal cortex was saturable with the dissociation constant (Kd) of about 0.6 nM and the maximum number of binding sites (Bmax) of 64 fmol/mg protein. Specific H1 antagonists, mepyramine (Ki = 1.4 nM), promethazine (Ki = 1.4 nM), diphenylpyraline (Ki = 4.1 nM), triprolidine (Ki = 5.3 nM), diphenylhydramine (Ki = 35 nM), but not the specific H2 antagonist, cimetidine (Ki greater than 10(5) nM), strongly inhibited the 3H-mepyramine binding. Regional distribution of the specific 3H-mepyramine binding was in the order of: frontal cortex greater than hippocampus greater than cerebellum greater than hypothalamus greater than thalamus, putamen, and pallidum. The specific 3H-mepyramine binding in schizophrenic brains was reduced by 56% in the frontal cortex. Representative Scatchard analyses of the specific 3H-mepyramine binding revealed changes resulting from a decrease in receptor density but not in receptor affinity. Down regulation of the histamine H1 receptor in the frontal cortex may be involved in the pathophysiology of schizophrenia. PMID- 1912126 TI - Essential and other fatty acids in plasma in schizophrenics and normal individuals from Japan. AB - Plasma phospholipid and cholesterol ester fatty acid levels were measured in samples from normal individuals, schizophrenics, and patients with affective and paranoid disorders in Japan. The schizophrenics were divided into groups with normal and reduced platelet sensitivity to the aggregation-inhibiting effects of prostaglandin (PG) E1. As in samples from schizophrenics in several other countries, linoleic acid levels were significantly below normal, as was the ratio of linoleic acid to its metabolites. Phospholipid fatty acid levels were normal in patients with paranoid or affective disorders. When the schizophrenics were divided into those with and without an abnormal response to PGE1, oleic acid was higher and eicosapentaenoic acid lower in those patients with an abnormal response. This study lends further support to the idea that schizophrenics may differ from controls in their essential fatty acid and eicosanoid metabolism. PMID- 1912127 TI - Lateralized abnormality in the EEG of persistently violent psychiatric inpatients. AB - Twenty-one consecutive right-handed male psychiatric inpatients treated on a unit designed for the management of violent behavior were given computerized EEGs. We recorded their violent behaviors, the number of staff interventions needed to control their behavior, and their medications. The number of instances of violence as well as the number of staff interventions were related to increased delta band activity and to decreased alpha band activity in the temporal and the parietooccipital areas. These relationships were independent of the current medications and of the length of stay on the special unit. Furthermore, our results demonstrate that violence is very significantly related to the hemispheric asymmetry in EEG for the frontotemporal derivations. With increased levels of violence there was a greater level of delta power in the left compared with the right. PMID- 1912128 TI - The effects of exogenous melatonin on the total sleep time and daytime alertness of chronic insomniacs: a preliminary study. AB - The effects of exogenous, supraphysiologic doses of melatonin on the total sleep time and daytime alertness of patients with chronic insomnia was examined in a double blind, single crossover study. Melatonin (75 mg per os) or identical placebo was administered at 10 PM daily to 13 insomniac patients for 14 consecutive days. A significant increase in the subjective assessment of total sleep time and daytime alertness was demonstrated with melatonin but not with placebo. However, 7 of the 13 patients reported that the active treatment had no significant effect on subjective feelings of well-being. PMID- 1912129 TI - Effect of fluoxetine on noradrenergic mediated growth hormone release: a double blind, placebo-controlled study. AB - Twelve patients with DSM-III-R major depressive illness were tested for growth hormone (GH) response to desipramine (DMI), a noradrenergic (NA) reuptake inhibitor. The response is mediated by NA alpha 2 receptors. They were then randomly assigned to treatment under double-blind conditions with either fluoxetine, the highly selective serotonin reuptake inhibitor or placebo. After 4 weeks they were retested. Fluoxetine but not placebo was effective in promoting recovery in four of the six patients treated. Patients treated with fluoxetine showed a significant decrease in DMI-mediated GH release irrespective of therapeutic outcome. This is consistent with marked alteration of NA function and raises questions as to the selectivity of fluoxetine. PMID- 1912130 TI - Limbic/mesolimbic connections and the pathogenesis of schizophrenia. AB - The development of models of the pathogenesis of neuropsychiatric diseases that build on recent advances in chemical neuroanatomy will help to guide future research. The interconnections among limbic, basal ganglia, and cortical structures are used to form the basis of a hypothesis of the pathogenesis of schizophrenia. The adaptive capacity of subcortical dopamine systems is advanced as an explanation of the many states of the disease. PMID- 1912131 TI - Manic psychosis after coffee and phenylpropanolamine. PMID- 1912132 TI - Nortriptyline in chronic fatigue syndrome: a double blind, placebo-controlled single case study. PMID- 1912133 TI - Enzymes of the antioxidant defense system in chronic schizophrenic patients. PMID- 1912134 TI - A double blind, placebo-controlled trial of demeclocycline treatment of polydipsia-hyponatremia in chronically psychotic patients. PMID- 1912135 TI - Impaired neuropsychological functioning in symptomatic volunteers with schizotypy: preliminary findings. PMID- 1912136 TI - [Animal and man--the problems of experimental and clinical research]. AB - The freedom of science includes human rights and animal rights and allows experimentation in both animals and human beings in case of ethical approval. The interpretation of results should be based on phylogenetic comparisons. Animal experiments can fulfill goals in human and veterinary situations, as it is demonstrated by caries and periodontal research. PMID- 1912137 TI - [The dynamics of bone apposition in different animal species--a comparative study]. AB - The time of the bone apposition was compared in rats, rabbits and guinea pigs with the aid of enzyme-activity measurements, determination of the proportion of minerals and the judgment of the cell generation. For this intention a defect was made in the distal femur epiphyses at the three species. The animals were observed for a term of 15 weeks. The results showed little differences with regard to the speed of the bone apposition in the three called species. The bone metabolism of rats was higher than those of the other ones. A clear reference value for the enzyme activity to a define point of time of the mineralization could not be ascertained. PMID- 1912138 TI - [Comparative research on the treatment of exposed bi- or trifurcations]. AB - S.E.M. comparison studies between different systems for bi- and/or trifurcation treatment, such as special curettes, ultrasonics and rotary diamond burs, were examined at thirty molars. The result show specific rough root surfaces in relation to the individual system. Curettes leaves the roughest root surface. PMID- 1912139 TI - [Periodontal status in Rio de Janeiro city (Brazil)]. AB - The periodontal status and the treatment needs were investigated in 1854 residents of Rio de Janeiro City (Brazil) by means of the CPITN. The results of the study showed that 2.5% of the examined individuals were healthy (CPITN 0), 8.1% displayed an increased tendency towards bleeding on probing (CPITN 1) and 23.2% presented with calculus and bleeding on probing (CPITN 2). Shallow pocketing (CPITN 3) was observed in 51.4% and deep pocketing (CPITN 4) in 14.7% of the examined subjects. Since 97.5% of the examined population were in need of periodontal therapy, the necessity for organizing an oral health program with emphasis on prevention and treatment of periodontal disease is strongly indicated. PMID- 1912140 TI - Epithelial-mesenchymal interactions in the development of salivary glands. AB - The full expression of both morphogenesis and secretory cell differentiation in salivary glands is modulated or controlled, at least in part, by interactions between the salivary epithelium and the surrounding mesenchyme. Salivary gland morphogenesis and cytodifferentiation are partially linked but independently regulated processes. This presentation reviews the information that establishes the role of various extracellular matrix molecules and direct epithelial mesenchymal interactions in the induction, control, and maintenance of morphogenesis and secretory cell differentiation in salivary glands. PMID- 1912141 TI - Drug-induced gingival overgrowth: old problem, new problem. PMID- 1912142 TI - The permeability of oral mucosa. AB - In discussing permeability, we are describing one of the fundamental barrier functions of oral mucosa. Despite assumptions to the contrary, the oral mucosa is not a uniformly, highly permeable tissue like gut, but shows regional variation. The keratinized areas, such as gingiva and hard palate, are least permeable and nonkeratinized lining areas are most permeable. This variation appears to reflect differences in the types of lipid making up the intercellular permeability barrier in the superficial layers of the epithelium. Differences in permeability may be related to regional differences in the prevalence of certain mucosal diseases and can be utilized to advantage for local and systemic drug delivery. PMID- 1912143 TI - Mastication and its control by the brain stem. AB - This review describes the patterns of mandibular movements that make up the whole sequence from ingestion to swallowing food, including the basic types of cycles and their phases. The roles of epithelial, periodontal, articular, and muscular receptors in the control of the movements are discussed. This is followed by a summary of our knowledge of the brain stem neurons that generate the basic pattern of mastication. It is suggested that the production of the rhythm, and of the opener and closer motoneuron bursts, are independent processes that are carried out by different groups of cells. After commenting on the relevant properties of the trigeminal and hypoglossal motoneurons, and of internuerons on the cortico-bulbar and reflex pathways, the way in which the pattern generating neurons modify sensory feedback is discussed. PMID- 1912144 TI - The role of complement in periodontal diseases. AB - The complement system has been implicated as both a pathogenic mechanism and a means of protection in periodontal diseases. It is well known that bacteria activate complement; such activation can initiate a number of events, including bacterial opsonization and killing, release of inflammatory agents, and modulation of other immune reactions. Cleavage of complement proteins has been observed in gingival fluids from individuals with periodontal disease and some investigators have observed complement deposition in diseased gingival tissues. Furthermore, a number of bacterial from individuals with periodontal diseases have been found to activate complement in vitro; some of these organisms appear to have the capacity to evade opsonization due to their proteolytic capacity. However, concrete evidence is not yet available that indicates that complement activation occurs in human periodontal disease and is important in either its pathogenesis or in protection against bacterial virulence factors. PMID- 1912145 TI - The concept of osseointegration and bone matrix expression. AB - Osseointegration has been defined as the direct structural and functional connection between ordered, living bone and the surface of a load-carrying implant. To date, this concept has been described by descriptive histological and ultrastructural criteria but not by biochemical means. This review evaluates the basic science work performed on this concept and then applies the concept to the principle of osseous healing. Specific studies are cited where alterations in the healing response are due to clinical management of implant placement and how studies of surface properties may lead to further insights on implant design and prognosis. In addition, a review of bone expression as a function of in vitro stress applications is given. This is followed by an indepth review of the collagens and noncollagenous proteins, described to date, within isolated bone matrix. It is this collagenous matrix (especially type I) that is described as being close to and oriented with a glycoprotein component next to the implant surface. In turn, the large family of noncollagenous proteins are important in mediating bone proliferation, matrix accumulation, orientation, mineralization, and turnover. This section is followed by a discussion of specific growth factors as they may relate to osseous healing around an implant. PMID- 1912146 TI - Genetic regulation of salivary proteins in rodents. AB - The presence of a protein in the cell is the result of a complex pathway that is known by the term gene expression. In this article we review the existing literature on the structure and expression of representative salivary gland genes and their regulated expression during development and upon extracellular stimulation. The expression of one of the "nuclear" protooncogenes, c-fos, in rat parotid glands is also discussed. Finally, we present some suggestions for future studies that will help to understand the mechanisms leading to gene regulation in rat salivary glands. PMID- 1912147 TI - Viruses and oral cancer. AB - Oral cancer is a disease with a complex etiology. There is evidence for important roles of smoking, drinking, and genetic susceptibility, as well as strong indications that DNA viruses could be involved. The herpes simplex virus type 1 has been associated with oral cancer by serological studies, and animal models and in vitro systems have demonstrated that it is capable of inducing oral cancer. Papillomaviruses are found in many oral cancers and are also capable of transforming cells to a malignant phenotype. However, both virus groups depend on co-factors for their carcinogenic effects. Future research on viruses and oral cancer is expected to clarify the role of these viruses, and this will lead to improvements in diagnosis and treatment of the disease. PMID- 1912148 TI - Factors in virulence expression and their role in periodontal disease pathogenesis. AB - The classic progression of the development of periodontitis with its associated formation of an inflammatory lesion is characterized by a highly reproducible microbiological progression of a Gram-positive microbiota to a highly pathogenic Gram-negative one. While this Gram-negative microbiota is estimated to consist of at least 300 different microbial species, it appears to consist of a very limited number of microbial species that are involved in the destruction of periodontal diseases. Among these "putative periodontopathic species" are members of the genera Porphyromonas, Bacteroides, Fusobacterium, Wolinella, Actinobacillus, Capnocytophaga, and Eikenella. While members of the genera Actinomyces and Streptococcus may not be directly involved in the microbial progression, these species do appear to be essential to the construction of the network of microbial species that comprise both the subgingival plaque matrix. The temporal fluctuation (emergence/disappearance) of members of this microbiota from the developing lesion appears to depend upon the physical interaction of the periodontal pocket inhabitants, as well as the utilization of the metabolic end products of the respective species intimately involved in the disease progression. A concerted action of the end-products of prokaryotic metabolism and the destruction of host tissues through the action of a large number of excreted proteolytic enzymes from several of these periodontopathogens contribute directly to the periodontal disease process.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1912149 TI - [Restenosis, the Achilles heel of coronary angioplasty]. PMID- 1912150 TI - [A clinical epidemiological study of Mediterranean boutonneuse fever in the Cartagena area]. AB - Clinical and epidemiological features of 72 cases of boutonneuse fever, detected from 1979 to 1986 at the "Hospital del Insalud de Cartagena" (Murcia), are reviewed. The most important clinical features are commented on (fever, rash, tache noire), as well as the less important (dizziness, cough, conjunctivitis, sensorial changes). Several epidemiological factors were analyzed, temperature having been found to be the most significant in our area. The complications observed mainly affected patients with risk factors (senility, thrombocytopenia, hyponatremia, high blood pressure) being particularly severe in a patient who developed lethal DIC and in another 2 who developed pulmonary thromboembolism. The prophylactic measures suggested were the strict control of animals susceptible to parasites and organizing of disinfestation campaigns in the endemic areas. PMID- 1912151 TI - [Subgroups of drug abuse patients who consume buprenorphine]. AB - We assessed the buprenorphine use in a sample of studied 184 patients with DSM III-R diagnostic criteria for opioid dependence who attended the Sta. Eulalia's CAS (outpatients facility) during 18 months period The lifetime prevalence of buprenorphine was 79% (43.5% of them were occasional users and 35.5% habitual; whereas the point prevalence was 16.8% (6.5% occasional users and 10.3% habitual). We compared the clinical characteristics of this patients, those who use the drug habitually and those who take it occasionally. The first group showed a longer time of opioid abuse (p less than 0.05) and they were more involved in drug traffic (p less than 0.001), mostly buprenorphine. These patients may present higher levels of clinical severity and social conflicts. Anyway they are usually polydrug users who consume more frequently flurnitracempan, cocaine, heroine, alcohol and cannabis (p less than 0.001). The usual ways of obtaining the buprenorphine are illegal traffic and GP's prescription in the Public health care facilities often by menace and intimidation. For consuming buprenorphine the abusers crush the pill, dilute it and them inject the solution i.v. The subgroup of patients who use buprenorphine occasionally only take in when don't have heroine and clinically they are not so deteriorated. PMID- 1912152 TI - [The use of oxygen as therapy in a general hospital]. AB - A prospective study of the therapeutic use of oxygen in a general hospital was carried out. 120 patients who received oxygen during the first 24 hours of their admission were included. Oxygen was prescribed continually for 113 patients (94%). This was administered with a Venturi mask in 116 patients (97%). Medium FiO2 prescribed initially was of 0.29 (SD = 0.04). Basal arterial blood gas measurement was performed on 101 patients (84%). PaO2 was equal to or lower than 60 mmHg in 69 (68%). Arterial blood gas measurement control was carried out in 51 patients (42.5%). Of the patients with basal PaO2 lower or equal to 60 mmHg, 44 (64%) were submitted to posterior control measurement. 32 of the latter group showed PaO2 higher than 60 mmHg. We observed important deficiencies: increased prescription in patients with PaO2 greater than 60 mmHg; the frequent noncontrol of arterial blood gas measurement; the lack of correction of FiO2 when the initial application of O2 did not increase the PaO2 higher than 60 mmHg. PMID- 1912153 TI - [The Budd-Chiari syndrome as the first manifestation of polycythemia vera]. AB - The case of a 57-year-old male diagnosed as having Budd-Chiari syndrome secondary to a polycythemia vera, which produced a thrombosis of the suprahepatic veins as a first manifestation, is presented. The rarity of this clinical case and the rapidly lethal evolution of the patient, confirms the bad prognosis of this association. PMID- 1912154 TI - [Leukocytoclastic vasculitis due to hypersensitivity to microfilariae]. AB - A case of a Caucasian girl with leukocytoclastic vasculitis, polyarthritis and eosinophilia is presented. A blood test showed microfilariasis, probably of the Loa Loa type. The epidemiology, clinical features, diagnosis and treatment of filariasis is described. In the western literature revised, reactive arthritis has been described but none of the other clinical features of our case. The presence of circulating immune complex might explain the pathogenic mechanism. We believe that filariae should be included amongst the causes of hypersensitivity vasculitis and in the differential diagnosis of eosinophilic vasculitis. PMID- 1912155 TI - [Mesenteric panniculitis. Apropos a case and a review of the literature]. AB - The case of a 35 year old female who had paraneoplasic syndrome during a period of one year, together with abdominal pain, is presented. Owing to the aforementioned, she was operated under the suspicion of lymphoma. The intraoperatory diagnosis was of retroperitoneal fibrosis. Physical examination showed important ascites and cachexia. Mild anemia and high sedimentation rate were found in blood test. A barium intestinal X-ray showed loop distention and a CT scan showed ascites and mesenteric thickening which were confirmed by a laparotomy. The histological study showed substantial cholagen and inflammatory infiltrate, together with giant cells of foreign body type. The different clinical presentations were reviewed as well as diagnoses, treatments, and the evolution of the disease. PMID- 1912156 TI - [Primary multicentric cerebral lymphoma in a previously healthy patient]. AB - Primary cerebral non-Hodgkin's lymphoma (PCL) is not very frequent, especially in the immunologically normal patient. Its radiological features and the response to steroid and radiotherapy treatment force the physician to consider it amongst the differential brain tumor diagnoses; particularly when an extraordinary remission is observed after steroid treatment, even in an immunologically normal patient. PMID- 1912157 TI - [The effect of different variables in the determination of plasma fibronectin in diabetes mellitus]. AB - Fibronectin is a high molecular weight glycoprotein which forms part of the basal membrane and is found in plasma that has suffered quantitative alterations during the development of various pathological processes. The aim of this paper is to study, in diabetic patients, the quantitative seric changes of this protein in relation to diabetes mellitus and the influence of different variables (type of diabetes, weight, sex, age, treatment involved, period of evolution and control of the disease according to glycemia and HbA1c). PMID- 1912158 TI - [Enteropathy due to the human immunodeficiency virus: a new entity?]. PMID- 1912159 TI - [Pure red-cell aplasia associated with rheumatoid arthritis]. PMID- 1912160 TI - [Acute myopathy due to triamcinolone acetonide]. PMID- 1912161 TI - [Lower respiratory tract infection by Pseudomonas stutzeri]. PMID- 1912162 TI - [Arterial hypertension secondary to an aldosterone-producing adenoma (APA)]. PMID- 1912163 TI - [Splenic hydatid cyst as the cause of a prolonged fever syndrome]. PMID- 1912164 TI - [Cardiac lymphoma as the initial presentation of AIDS]. PMID- 1912165 TI - [Pregnancy and benign intracranial hypertension]. AB - Several papers have suggested that pregnancy is one of the etiopathogenic factors of benign intracranial hypertension (BIH). The therapeutic attitude to be taken as regards new pregnancies in women previously afflicted with BIH during pregnancy is still on discussion. This paper is based on a study of 100 BIH cases. The results support the idea that cases, but the obesity involved. The coexistence of BIH and pregnancy does not increase the risk of relapse, does not mean a worse prognosis of BIH nor does it appear to have a negative effect on the child. Any woman who has previously developed BIH during pregnancy should not be advised against future pregnancies. In the case of a new pregnancy, a very close control should be carried out in order to avoid an excessive increase in weight. PMID- 1912166 TI - [Porphyria cutanea tarda]. PMID- 1912167 TI - [Giant-cell arteritis: the clinico-biological manifestations and the complications secondary to steroid treatment]. AB - The analysed clinico-biological manifestations, evolutive course and treatment of 30 patients with GCA are presented. The most frequent symptoms were fever and headache. 33% of patients had FOD criteria. 26% had various visual alterations. All patients were initially treated with steroids. Of the 26 patients followed up, 21 (81.7%) experienced some sort of complication: Cushing iatrogenic, osteoporosis, vertebrae collapse, aseptic necrosis of the femur head, arterial hypertension, diabetes mellitus, hyperlipidemia, steroid myopathy. 6 patients were treated with cyclophosphamide, following severe complications secondary to steroid therapy, and all of them had a good clinical evolution. PMID- 1912168 TI - [Lymphocyte subpopulations in rheumatoid arthritis patients, their relatives and spouses]. AB - A study of lymphocytic sub-populations of patients with rheumatoid arthritis, their families and partners, is presented. The determination was carried out by means of monoclonal antibodies, analysing: T cells sub-population (CD3, CD4, CD8 and quotient CD4/CD8); B cells sub-population (B1); activated cells (OK1a); monocytes and NK cells (OKM1 and BMA 070). The results showed an increase of CD3 sub-population (T total lymphocytes) in patients with RA and their families. The meaning of these results is difficult to evaluate as lymphocyte sub-population is affected by several variables. The lack of modification of suppressor population, CD4/CD8 quotient and IKM1 cells in RA patients is probably due to the moderate activity of the disease. PMID- 1912169 TI - [The hematological manifestations in 111 patients with systemic lupus erythematosus]. AB - Hematologic alterations are frequent in SLE. The hematologic changes of 111 patients diagnosed as suffering from SLE are described, associating them to 89 clinical, biological and hystological variables. The most frequent alteration was normocytic and normochromic anemia. Coombs positive hemolytic anemia appeared in 10% of the cases. Approximately 20% of patients had leukopenia. Lymphopenia was observed during the active period of the disease. Mild thrombocytopenia is common, as well as quality changes of the platelets. The sedimentation rate is high in nearly all patients with SLE and this is a non-specific index of the disease activity. These changes have seldom been described in our area. PMID- 1912170 TI - [Obesity and autonomic neuropathy in non-insulin-dependent diabetes mellitus]. AB - It has been said that the presence of autonomic neuropathy is related to the onset of obesity. Given the high prevalence of association between autonomic neuropathy and Diabetes Mellitus and the association between metabolic disease and obesity, we considered it important to evaluate the possible relationship in order to ascertain the pathogenic connection and its impact on therapy. We evaluated 2 groups of diabetic patients: one group was composed of obese patients and the other of non-obese. According to our results, there appears to be no relationship between autonomic neuropathy and obesity, at least in patients with diabetes mellitus type II. PMID- 1912171 TI - [Severe metabolic alkalosis during hemodialysis]. AB - Severe metabolic alkalosis in a patient while being hemodialysed with dialysate of bicarbonate is presented. The evolution was satisfactory after a session of hemodialysis with a bath of acetate. Disorders in the acid-base balance which appear following dialytic technics more complex each time are discussed. PMID- 1912174 TI - [Systemic nocardiosis with cerebral abscesses in a kidney transplant patient]. AB - A 44-year-old renal transplant recipient, developed a systemic nocardiosis with cerebral abscess and without pulmonary involvement. Immunosuppressive therapy was discontinued and combination of surgical drainage procedures and prolonged chemotherapy with TMP/SMX were successful. His renal function remained stable and he has had no recurrence of nocardiosis. PMID- 1912173 TI - [Starch-induced granulomatous peritonitis]. AB - A case of granulomatous peritonitis produced by starch is presented. This is a rare pathology caused by abdominal contamination with starch from surgical gloves during an operation. The symptoms can be very similar to acute abdomen, therefore, it is sometimes necessary to carry out a second operation in order to confirm the diagnosis. A peritoneal biopsy or cytology of the ascitic liquid usually provides the correct diagnosis as the typical starch granules show up. With non-steroid analgesics, or steroids in some cases, the process can controlled. PMID- 1912175 TI - [Giant-cell arteritis: the diagnostic and therapeutic controversies]. PMID- 1912172 TI - [The total absence of xanthine oxidase activity. Apropos 2 cases of the nonfamilial incidence of xanthinuria]. AB - The lack of activity of the xanthine-oxidase conversion produces hypouricemia and hypocuria, with high urine elimination of xanthine and hypoxanthine. Due to the low solubility, it can result in urinary lithiasis. Two rare cases of xanthinuria caused by total lack of xanthine-oxidase are presented. A differential diagnosis of several congenital metabolic purine defects was carried out. PMID- 1912178 TI - [Idiopathic granulomatous myopathy. An evolutionary study]. PMID- 1912177 TI - [The diagnostic and therapeutic outlooks in the diffuse pulmonary hemorrhage syndrome]. AB - Diffuse pulmonary hemorrhage syndrome (DPHS) is reviewed and classified according to the international classification. We analyse the more characteristic features, as well as the most appropriate diagnosis methods which ensure early and effective treatment. We conclude by proposing the therapeutic attitude to be taken for DPHS. PMID- 1912179 TI - [Cefonicid efficacy in the treatment of community-acquired pneumonia]. PMID- 1912176 TI - [The role of leukotrienes and other eicosanoids in the response to an allograft. New perspectives on the control of rejection]. AB - The role of eicosanoids in the development of immune response may be important to the viability of the implanted organ, given their complicated interaction with lymphokines and monokines which regulate the response. Due to this reason, more experiments in vivo are necessary to provide a better understanding of the behaviour of these compounds. This would help to clearly determine the role of these substances in the immune response--more exactly, in the allogenic transplant rejection--creating new ways for its control. PMID- 1912180 TI - [Gilbert's syndrome and cholesterolosis]. PMID- 1912181 TI - [Sarcoidosis and lymphoma: a case report]. PMID- 1912182 TI - [Erythema nodosum: an unusual form of presentation of Hodgkin's disease]. PMID- 1912183 TI - [Pneumocystis carinii pneumonia and spontaneous pneumothorax]. PMID- 1912184 TI - [Lung adenocarcinoma, monoclonal gammapathy and scleroderma]. PMID- 1912185 TI - [Visceral leishmaniasis and HIV infection: 2 new cases]. PMID- 1912186 TI - [Nocturnal asthma]. PMID- 1912187 TI - [Capillaroscopy in vasculitis]. AB - A prospective study of the capillaroscopy changes in 15 patients afflicted with vasculitis is presented. 2 of them had classic polyarteritis nodos (PAN), 3 had Churg-Strauss allergic angiitis and granulomatosis, 2 had hypersensitivity vasculitis (HV), 6 had giant-cell arteritis (GCA) and 2 had polyangiitis overlap syndrome (POS). Periungual capillaroscopy (PC) showed isolated changes in 11 patients (73%). We observed more changes in those cases with active disease (83% vs. 67%); they were mainly microhemorrhage (without any statistical significance). There were no more findings in patients with a more generalised affliction (nervous system, kidneys and/or skin) than in the others. In conclusion, the capillaroscopy findings were few and non-specific. PC is a diagnostic method of negligible value in this type of disease. PMID- 1912188 TI - [Atrial fibrillation and cerebral infarct]. AB - The importance of atrial fibrillation (AF) as a risk factor (RF) for cerebral infarction (CI) is well-known. It is probably caused by cardiac embolism but other explanations can also justify this association. Our aim was to analyse the features of the patients with CI and AF and sinus rhythm (SR), as well as to form hypotheses as regards the pathogenesis. 250 patients with CI, 204 in RS and 46 in AF (31 non-valvular and 15 associated to a valvular disease) were studied, analysing the prevalence of RF and initial blood tests. The group of patients with valvular AF of probably embolic mechanism had a minor prevalence of RF (hypertension, diabetes, smoking, alcoholism) but higher mortality. The group with non-valvular AF, had a lower RF prevalence compared to the SR group (non embolic mechanism), without statistical significance and with a similar mortality rate. We concluded that the atherothrombotic mechanism can be the cause of a considerable proportion of CI in patients with non-valvular AF. PMID- 1912189 TI - [Bone mass peak, evaluation using bone densitometry of the whole body in a normal female population in our environment]. AB - Considerable debate exists about when the maximal bone mass, or "bone mass peak" is physiological acquired. In the present study, 140 normal females aged 15 through 19 years (n = 18), 20 through 29 years (n = 58) and 30 through 39 years (n = 64), were assessed in order to determine their total body bone mineral (TBBM) content, as bone mass parameter, by bone densitometry with dual energy X rays. We did not observe significant differences in TBBM values between the different groups. A positive and significant correlation existed between age and TBBM (r = 0.486, p less than 0.05) in female aged 15 to 19 years but not in the rest of the groups. These data suggest that female acquired their maximal bone mass, or bone mass peak, up to the age of 20 years and that it remains stable until, at lest, the age of 39 years. We point up the importance of achieving an adequate skeletal development in females during their first 20 years of life that could perhaps protect them from suffering subsequently from osteoporosis. PMID- 1912191 TI - [Necrotic leukoencephalitis, a new infrequent form of presentation of HIV encephalopathy]. AB - A case of a female infected by HIV whose first manifestation was a focal defect of the motor function caused by a brain lesion shown in the CT scan and NMR as a hemispheric mass with discreet expansive effect and central necrosis. The histologic study showed a necrotic leukoencephalitis related to HIV as etiologic agent. We point out the difficulties in diagnosing and treating this disease. PMID- 1912190 TI - [Prevalence of antibodies against Coxiella burnetii in a healthy population in Lanzarote (Canary Islands)]. AB - The Canary Islands area now appears to be a Q-fever endemic zone, especially the west side (La Palma island). The situation in the eastern islands in unknown. In order to evaluate the seric prevalence of Coxiella burnetii, 100 serum samples that were taken from the adult population of Lanzarote and, following strict criteria, were analysed using a complement fixation test; blood donors and patients who had suffered a recent infection were excluded. The study was carried out during November/1986. Three serum samples were positive, one had titers of 1/8 and the other two showed 1/64. This prevalence rate of residual Coxiella burnetii antibodies in Lanzarote (3%)--despite being low compared to other areas in Spain--together with te recent cases described, confirms the suspicion that the Canary Islands area is indeed a new endemic Q-fever zone. PMID- 1912192 TI - [Intrapericardial pheochromocytoma]. AB - Intrapericardial pheochromocytomas are extremely rare tumors. Diagnosing and localizing them are very difficult tasks when using conventional methods used for adrenal pheochromocytoma. We present the case of a patient with a pheochromocytoma who had a CT scan of the thorax and abdomen performed, as well as 131I methaiodinebencilguanidin (131 I-MIBG) gammagraphy, with completely normal results. The tumor was localized in the mediastinal area using 123 I-MIBG and NMR. The tumor was found intrapericardial during the operation; it was fixed to the pulmonary artery and in close contact with the left atrial, as well as with the circumflex and aorta arteries. It was possible to carry out the resection without causing any damage to these structures. PMID- 1912193 TI - [Rickettsia conorii: a new cause of erythema nodosum]. AB - A case of 26 year old male with an infection caused by Rickettsia conorii (RC) associated to erythema nodosum (EN) is presented. The patient had EN together with a high temperature and toxic symptoms 2 weeks after camping in the mountains. The diagnosis was made by ascertaining IgM titers positive to RC by indirect immunofluorescence (IIF). The disease disappeared 24 hours after the initiation of treatment with doxiciclin. Based on this observation, we consider RC to be an etiologic agent which should be taken into account in the differential diagnosis of EN. PMID- 1912194 TI - [Cardiac diseases related to free radicals and active species of oxygen. Biochemistry (1)]. AB - In the first part of this paper, a group of definitions are explained in order to understand the mechanisms groups of the most important enzymes which participate in the formations of free radicals and active species of oxygen in the heart. Furthermore, we focus on chemistry and the production of these different active species of oxygen, rounding of by giving information related to the importance of hypoxia-reoxygenation, as well as the lipidic peroxidation in the formation of oxygen free radicals. All this information provides us with a biochemical baseline to write a second part about the cardiovascular pathology related to the lack of equilibrium between pro-oxidation and anti-oxidation. PMID- 1912195 TI - [Localized bone gigantism and neurofibromatosis]. PMID- 1912196 TI - [Antiphospholipid antibodies in Q fever]. PMID- 1912197 TI - [Efficacy of nicotine gum in the cessation of the smoking habit]. PMID- 1912198 TI - [Subacute thyroiditis and prolonged febrile syndrome. A new case]. PMID- 1912199 TI - [Does chronic hypoxemia favor the appearance of paragangliomas?]. PMID- 1912200 TI - [Solitary hypertransaminasemia associated with a hypernephroma: Stauffer's syndrome]. PMID- 1912201 TI - [Pulseless disease as presenting form of temporal arteritis]. PMID- 1912202 TI - [Leukocytoclastic vasculitis associated with a multisystemic involvement]. PMID- 1912203 TI - [Metabolic encephalopathy secondary to lithium poisoning: presentation of a case]. PMID- 1912204 TI - [Multiple myeloma and pulmonary involvement]. PMID- 1912205 TI - [Primary care in mental health]. PMID- 1912206 TI - [Two systems of persuasion to quit smoking. A controlled trial]. AB - The effectiveness of two systems of persuasion for persons willing to quit smoking was compared in the context of health educational activities: the traditional method (TN), based on the warning of the risk of disease and death, and a method of positive reinforcement focused on the better quality of life and health level (TP. The study had a controlled trial format, with three randomized groups: One with TN, receiving the traditional negative approach; other with TP, the positive treatment; and another group without therapy. After a 15, 30, 60 and 90 days of follow-up it could not be shown that TP is superior to TN. The former appeared as more effective but without significant differences. PMID- 1912208 TI - [The computer in primary care: dream and reality]. PMID- 1912207 TI - [Quantitative pharmaceutical indicators and reform: do they change when there are no staff changes?]. AB - The evolution of three quantitative pharmaceutical indicators before and after the reformation was implemented in three ABS from Girona and in the rest of the province with non-reformed system of care was evaluated. The three investigated ABS, after a period of reformation with similar characteristics, showed a quite different evolution of their pharmaceutical indicators. The comparison of the increments of the indicators among the different centers did not show significant differences in the years preceding the reformation. The differences appeared when the comparison was made after the reformation: amount/prescription (p less than 0.01), amount/inhabitant (p = 0.01), and number of prescriptions/inhabitant (p = 0.01). The three ABS contributed to these differences in a different sense and in unequal degrees. The study did not address the quality of prescription. However, it showed its varied evolution after the reformation, as shown by the three evaluated indicators. Factors other than the characteristics of the system where health care is included appear to have greater importance in the short run. PMID- 1912209 TI - [Multicenter evaluation of a diabetes program in primary care in Tarragona]. AB - To evaluate a provincial diabetes program for primary care in Tarragona 14 months after its implementation, the data provided by all centers were evaluated. The participants were 8 CAPS and the professionals of a rural area, with a reference population of 170,159. A total of 1,766 diabetic patients were sensed. 131 were type I (7.4%) and 1,635 type II (90.6%). The health care variables of 1,197 patients (67.7%) and the rate of complications of 654 (54.6%) were assessed. A high prevalence of hypertension (50.0%) and dyslipemia (40.5%) were found associated with diabetes. Overall 868 individuals (72.5%) received individualized education in the clinic; 112 of these (12.9%) were included in collective education programs for groups. At the time of this evaluation, the proportion of patients treated with insulin (174/545) was significantly higher than that found before the program (79/402, p less than 0.0001). The practice of glycemic self assessment at home was also significantly increased (82/691 versus 440/1, 124; p less than 0.0001). The initial impact on the professional and diabetic patients of our area has been remarkable. Although the planning of multicentric evaluation systems in complex, it is possible to implement it if the data and recording system are coordinated. PMID- 1912210 TI - [Hospital follow-up of referred patients over a year from the emergency service at a rural health center]. AB - We have evaluated the patients that were referred to the referencie hospital from the emergency service of our health center between July 1, 1988, and June 31, 1989, and we have followed them up after their arrival to the hospital. We had cared for 20,546 emergencies, particularly from internal medicine, pediatrics and pediatric surgery, traumatology, plastic surgery and neurosurgery. 636 of these were referred (3.09%), with varying rates for specialities, from 7.1% in gynecology to 0% in dermatology. Only 436 of the referred patients attended the hospital. Of these, 49.3% were discharged, 30.5% were admitted and 20.2% were kept for observation up to 48 hours. The highest rates of admissions were seen in internal medicine, pediatrics and pediatric surgery, general surgery, gynecology and psychiatry. All patients from otorhyno-laringology were discharged, and so were 83.8% from ophthalmology and 62.8% from traumatology-plastic surgery neurosurgery. It was concluded that there is a need for an improved continuing education of the staff (particularly in some areas of medicine), and better material resources and health education. PMID- 1912211 TI - [Family outbreak of hepatitis B]. AB - Hepatitis B virus (HBV) causes one of the most widespread infections worldwide. We report a family outbreak where a male with Down's syndrome attending an open institution for mentally retarded individuals probably was the source of the infection. We consider the prevention as the only means to attack the infection with intervention on the transmission mechanisms and immuniprophylaxis. We emphasize eh need of a perfect communication between the several institutions involved in epidemiological surveillance. This might have prevented the present outbreak. Finally, we insist on the importance that the primary care physician could have in the prescription and indication of immunoprophylaxis. To this end, the disappearance of the administrative barriers established by the Secretaria General de Asistencia Sanitaria from the Health Ministry would be needed. PMID- 1912212 TI - [Clinical interview]. PMID- 1912213 TI - [Esophageal diseases]. PMID- 1912214 TI - [Non-parametric tests in the statistical analysis of data]. PMID- 1912215 TI - [Incidence of influenza episodes at a health care center]. PMID- 1912216 TI - [A case of tetanus seen in primary care]. PMID- 1912217 TI - [Carcinoma of the gastric stump in primary care]. PMID- 1912218 TI - [Palpebral pediculosis at a health center]. PMID- 1912219 TI - [Saturnism: a challenge for primary care]. PMID- 1912220 TI - [Maprotiline in primary care. Electrocardiographic changes]. PMID- 1912221 TI - [Procedure to follow in cases of shift change between 2 physicians. Our case]. PMID- 1912222 TI - [Serum creatinine as indicator of renal function in the geriatric population]. PMID- 1912223 TI - [Research in primary care]. PMID- 1912224 TI - [Programming in primary care]. PMID- 1912225 TI - [Brief questionnaires for the early detection of alcoholism in primary health care]. AB - The utility of two tests for the early detection of alcoholism (CBA and CAGE) is studied in a group of 247 adult patients of both sexes at the primary care environment. For the definition of the "problem drinker case", the Munchner alkoholismus test (MALT) protocol is used as "gold standard". A sensitiveness of 79 and 75% is obtained for the CBA and CAGE respectively, a specifity of 94 and 96%, and predictive positive value of 63 and 73%, with a prevalence of "problematic drinkers" of 12%. Both questionnaires are shown as efficient instruments for the secundary prevention of alcoholism in the primary care consulting rooms. PMID- 1912226 TI - [Yield of health exam in a rural school population]. AB - The yield of the health status examination and associated factors in schoolchildren was assessed in the Primary Health Care center at Les Borges Blanques (Lerida), by means of the detection of abnormalities unknown by the parents receiving treatment. A self-administered questionnaire before the examination permitted to identify the already known abnormalities. Subsequently, a personal interview evaluated the follow-up. A total of 252 schoolchildren were evaluated, and 327 abnormalities were detected; 111 of these were unknown to the parents (33.94%); less than one half (48) presented for confirmation of the diagnosis. The diagnosis was confirmed in 44, treatment being prescribed in 36. In 33 schoolchildren (13.09%) the examination could have been useful. The observed low yield may be accounted for by the small rate of families that present for confirmation of the diagnosis. The personal communication of the diagnosis to the parents and the follow-up of cases might improve the yield. PMID- 1912227 TI - [Prevalence of cognitive deterioration in a geriatric urban population]. AB - A descriptive study was carried out in Salt (Gerona) to evaluate the prevalence of cognitive impairment in a geriatric urban population and its relation with several variables which might have an influence on it. The cognitive status was evaluated with the score in the Mini-Mental State Examination (MMSE). A representative sample of 392 individuals was obtained out of an overall population of 2,394 registered persons above 65 years of age; 354 of them were interviewed. The overall rate of intellectual deterioration (MMSE less than 24) was 26.5%, and it was 8% for the important deterioration (MMSE less than 18). The presence of cognitive impairment was significantly correlated in multivariate analysis with advanced age, low educational level and limited personal autonomy. PMID- 1912228 TI - [Family planning: a need in primary care]. AB - The reformation of Primary Care (PC) permits a more satisfactory and coordinated approach to family planning (FP). We evaluated the profile of the potential users of FP by means of a survey of 182 females made in a Primary Care center (CAP). The most commonly used contraceptive methods were oral contraceptives (20.3%), coitus interruptus (Cl) (18%), condom (17%) and female sterilization (12.6%). 66.6% of failures were attributed to Cl. 32.25% of the intrauterine device users and 24.4% of those taking oral contraceptives reported problems. 24.7% of females were controlled in the CAP II, 19.7% by their private gynecologist, 16.5% in the municipal CP and 6% in the CAP. 30.2% of the users did not follow and type of control. PMID- 1912229 TI - [Reliability of the delayed reading of reactive strips of capillary blood glucose]. AB - To assess the realibility of delayed readings of the reactive strips for glycemia BM-test 20-8, obtained by patients at their home and read in the health center both according to the Boehringer color scale and by reflectometer Reflolux II, we assessed 100 strips. One half were stored in opaque tubes and the rest were exposed to the light, all at room temperature. They were read both visually and with reflectometer Reflolux II in a programmed fashion on the days 0, 1, 3, 5, 7, 10 and 14. The results showed that the accuracy of the color scale as compared with the reflectometer depended on the levels of glycemia (owing to the scale intervals), without significant differences. Regarding the delayed reading in the strips kept away from light, there was a statistically significant reduction of 7 mg/dl on the third day. According to the regression analysis, the strips lose 2 mg/dl each day. In the strips exposed to the light, the measurement loss on the 14th day is significantly greater than in strips removed from light. PMID- 1912230 TI - [Program for helping the smoker in primary care. Preliminary evaluation]. AB - The program of help to the smoker (PHS) consists of a systematic intervention upon the whole of the demanding population, identifying the smokers and acting on them with a short, concise advise in all visits. The results after 2 months of operation of the PHS in a primary care center are reported. Among 483 persons 104 smokers were detected (23.65%). 27% showed a favorable disposition towards quitting smoking within a short term; only 17% declared to be against quitting. The best response (36.8% of favorable responses) was obtained in the group smoking 20 cigarettes per day or more. The reported data suggest that the PHS could be useful both in heavy and in minimal or moderate smokers. We consider these data as a preliminary evaluation; assessment with data of long term cessation from smoking is required. PMID- 1912231 TI - [The R3SPE syndrome. Presentation of 3 clinical cases]. AB - The R3SPE syndrome represents a new disorder included in the inflammatory rheumatisms of old age, being related to rheumatoid arthritis. It differs from the latter in some clinical and evolutive peculiarities. Its etiology and pathogenesis are unknown. The best treatment, purely symptomatic, consists of the association of aspirin and synthetic antimalarial drugs. Low-dose corticosteroids are very effective in initial stages. We report three patients and their clinical, evolutive and therapeutic features. PMID- 1912232 TI - [Psychosis and psychotic behavior]. PMID- 1912233 TI - [Special explorations in the gastrointestinal tract]. PMID- 1912234 TI - [A new perspective in quality assurance: the quality circles]. PMID- 1912235 TI - [Rural medicine in family and community medicine education as a specialty]. PMID- 1912236 TI - [Reflex sympathetic dystrophy caused by drugs]. PMID- 1912237 TI - [Qualitative studies on drug prescription in primary care]. PMID- 1912238 TI - [Complementary steps to increase coverage of the anti-influenza vaccine]. PMID- 1912239 TI - [Mediterranean boutonneuse fever, Epidemiology, diagnosis and treatment in primary care]. PMID- 1912240 TI - [Gilbert's syndrome in primary care]. PMID- 1912241 TI - [Record cards of prolonged treatment]. PMID- 1912242 TI - [Saturnism and health education]. PMID- 1912243 TI - Molecular-biological and immunological properties of ribosomal vaccines. AB - Data on the immunological properties and protective action of ribosomal vaccines are reviewed from the point of view of the structural and functional properties of ribosomes. Comparative analyses are presented for ribosomes from Gram-negative and Gram-positive microorganisms, and for ribosomes from prokaryotes and eukaryotes. Special consideration is given to the nature of the protective factors of ribosomal preparations and the mechanisms of ribosomal vaccine immunogenesis. PMID- 1912244 TI - Recognition of classical genetics by the Kremlin. PMID- 1912245 TI - Treatment of experimental genital herpes with liposomal interferon. AB - The therapeutic effect of genetically engineered interferon (reaferon) in the treatment of genital herpes in male guinea pigs was studied. The disease was induced in the animals by application of culture liquid containing herpes simplex virus type 2 (HSV-2) to the scarified skin of the penis. The affected sites were treated once daily, for 7 days, with different reaferon preparations 1-3 days after the symptoms of the disease had appeared. Reaferon preparations were most effective in the treatment of experimentally induced genital herpes when incorporated into liposomes, had a less pronounced therapeutic effect when mixed with 3% deoxymethylcellulose to form a hydrocolloid, and were least effective in aqueous solution. Incorporation of the antiviral agents acyclovir and Biolf-62 into liposomes also showed improved effectiveness, in comparison with the free compounds, in the treatment of genital herpes in guinea pigs. PMID- 1912246 TI - Direct recording of postcapillary resistance in cat skeletal muscle: measurement in the presence of humoral stimuli. AB - A procedure involving the parallel perfusion of deep veins in a cat shank preparation with endogenous blood and a constant volume of dextran solution has been devised. The dextran is supplied to these deep veins via superficial and communicator veins (venae communicantes). With this method it is possible to record dynamic changes in the resistance of the deep veins (postcapillary resistance) in response to intraarterial administration of vasoactive agents into the vascular bed of the shank. Data are presented which indicate that the number of deep veins involved in the changes in venous resistance is equivalent to 67% of the total capacity of the vascular bed of the shank. It is shown that the increase in venous perfusion pressure caused by infusion of noradrenaline into the vascular bed of the shank is essentially equivalent to the increase in mean capillary pressure as determined isovolumetrically. With this new method it is demonstrated for the first time that angiotensin II causes constriction of the deep veins of the shank and that isoproterenol causes dose-dependent dilatatory reactions in the veins within the muscle preparation. PMID- 1912247 TI - Dynamic model of 99mTc-labelled lipoprotein accumulation in rabbit liver. AB - To create a mathematical model to describe the receptor-mediated accumulation of 99mTc-labelled lipoproteins in rabbit liver, a set of differential equations was devised for the simplest case: that involving one ligand and one receptor. Normal and hypercholesterolemic rabbits were included in gammascintigraphic trials as having normal and reduced numbers, respectively, of liver low-density lipoprotein (LDL) receptors. The system described may have clinical applications as a quick and effective method of assessment of LDL uptake by the liver. PMID- 1912248 TI - Flow-injection glucose determination with long-wavelength luminescent oxygen probes. AB - A flow-injection method for the determination of glucose in serum is presented. It is based on the enzymatic measurement of oxygen consumption detected via oxygen quenching of the luminescence of certain metalloporphyrins. Phosphorescent water-soluble Pt2+ and Pd(2+)-porphyrins have been characterized by luminescence spectroscopy and decay-time measurements in various buffers, and found to be suitable for oxygen detection in biological systems. A new method for the flow injection analysis of glucose has been developed based on the use of a column of immobilized glucose oxidase and the indicators Pt(2+)-coproporphyrin III and Pd(2+)-coproporphyrin I. The system has been optimized for glucose determination in aqueous samples and in whole serum with the 0.5-200 mM glucose range. Twenty assays can be performed in an hour, and the system has potential for commercial development with biotechnological and medical applications. PMID- 1912249 TI - Effects of carnosine, a specific component of striated muscle, on muscle and other tissues. PMID- 1912251 TI - On the ionic cyclotron resonance in biomolecules. PMID- 1912250 TI - ADP-ribosyltransferase activity of Legionella pneumophila is stimulated by the presence of macrophage lysates. AB - ADP-ribosyltransferases are among the most biologically active of bacterial products in eukaryotes, and act by transferring the ADP-ribosyl moiety of NAD to acceptor proteins. The detection of ADP-ribosylated Legionella proteins in ultrasonic lysates of Legionella pneumophila strain Philadelphia 1 is reported. The ADP-ribosylating reaction was not influenced by addition of guinea pig spleen cell and lung-cell lysates, but was considerably increased in the presence of lysates of guinea pig peritoneal macrophages, which are known to be target cells for virulent Legionella. It is suggested that ADP-ribosylation may play an important role in the multiplication of this pathogenic bacterium in the tissues and cells of infected organisms. PMID- 1912252 TI - The 2 x 2 matched-pairs trial: exact unconditional design and analysis. AB - An exact unconditional method for the design and analysis of the 2 x 2 matched pairs trial is presented. Unlike the exact conditional method, which is based on only the number of discordant pairs, the exact unconditional method uses the total number N of sampled pairs. This unconditional test, based on a simple Z statistic, yields sample sizes that are generally smaller than those produced by the exact conditional test for the cases tabulated herein, namely one-sided alpha = .01, .025, and .05 along with 80% and 90% power. Moreover, it is found to be uniformly more powerful than the latter for all the combinations of parameters considered in this paper, namely alpha = .01, .025, and .05, and N = 10(1)200. The method is illustrated by assessing various design options of an in vitro study of the effectiveness of antimicrobial agents. Some numerical examples of matching efficiency are also given. PMID- 1912253 TI - Robust estimation of the variance in moment methods for extra-binomial and extra Poisson variation. AB - When faced with data in the form of overdispersed counts or proportions, moment methods allow consistent parameter estimation when only the form of the mean and variance is specified. If the variance form is misspecified, these methods still yield consistent parameter estimates, though with lower efficiency, and the variances of the estimates will be inconsistent. A variance correction is available that yields consistent variance estimates in these circumstances. The asymptotic and small-sample efficiencies of this correction are calculated, and its performance under variance misspecification is studied. A group-randomized breast self-examination prevention study that is now underway serves as a focal point for the study of these properties. The use of the variance correction in modelling is illustrated on a teratology data set. PMID- 1912254 TI - Modelling sub-binomial variation in the frequency of sex combinations in litters of pigs. AB - In some samples of pig litters, the number of males per litter exhibits significant sub-binomial dispersion: there are fewer unisexual and more "sex balanced" litters than expected under a binomial model. It is argued here that the explanation is that the sex of zygotes may be subject to hormonal control with the consequence that, within a litter, the zygotes do not all have the same probability of being male. This variation in probability is approximated by a quadratic function of the time during oestrus that a zygote is formed so as to parallel the variation in maternal hormone levels. Other explanations are examined briefly, but each seems to have serious weaknesses. PMID- 1912255 TI - Regression with frailty in survival analysis. AB - In studies of survival, the hazard function for each individual may depend on observed risk variables but usually not all such variables are known or measurable. This unknown factor of the hazard function is usually termed the individual heterogeneity or frailty. When survival is time to the occurrence of a particular type of event and more than one such time may be obtained for each individual, frailty is a common factor among such recurrence times. A model including frailty is fitted to such repeated measures of recurrence times. PMID- 1912256 TI - A Monte Carlo method for Bayesian inference in frailty models. AB - Many analyses in epidemiological and prognostic studies and in studies of event history data require methods that allow for unobserved covariates or "frailties." Clayton and Cuzick (1985, Journal of the Royal Statistical Society, Series A 148, 82-117) proposed a generalization of the proportional hazards model that implemented such random effects, but the proof of the asymptotic properties of the method remains elusive, and practical experience suggests that the likelihoods may be markedly nonquadratic. This paper sets out a Bayesian representation of the model in the spirit of Kalbfleisch (1978, Journal of the Royal Statistical Society, Series B 40, 214-221) and discusses inference using Monte Carlo methods. PMID- 1912257 TI - A comparison of exact, mid-P, and score tests for matched case-control studies. AB - A recently developed algorithm for generating the distribution of sufficient statistics for conditional logistic models can be put to a twofold use. First, it provides an avenue for performing inference for matched case-control studies that does not rely on the assumption of a large sample size. Second, joint distributions generated by this algorithm can be used to make comparisons of various inferential procedures that are free from Monte Carlo sampling errors. In this paper, these two features of the algorithm are utilized to compare small sample properties of the exact, mid-P value, and score tests for a conditional logistic model with two unmatched binary covariates. Both uniparametric and multiparametric tests, performed at a nominal significance level of .05, were studied. It was found that the actual significance levels of the mid-P test tend to be closer to the nominal level when compared with those of the other two tests. PMID- 1912258 TI - Procedures for two-sample comparisons with multiple endpoints controlling the experimentwise error rate. AB - Clinical trials are often concerned with the comparison of two treatment groups with multiple endpoints. As alternatives to the commonly used methods, the T2 test and the Bonferroni method, O'Brien (1984, Biometrics 40, 1079-1087) proposes tests based on statistics that are simple or weighted sums of the single endpoints. This approach turns out to be powerful if all treatment differences are in the same direction [compare Pocock, Geller, and Tsiatis (1987, Biometrics 43, 487-498)]. The disadvantage of these multivariate methods is that they are suitable only for demonstrating a global difference, whereas the clinician is further interested in which specific endpoints or sets of endpoints actually caused this difference. It is shown here that all tests are suitable for the construction of a closed multiple test procedure where, after the rejection of the global hypothesis, all lower-dimensional marginal hypotheses and finally the single hypotheses are tested step by step. This procedure controls the experimentwise error rate. It is just as powerful as the multivariate test and, in addition, it is possible to detect significant differences between the endpoints or sets of endpoints. PMID- 1912259 TI - Nonparametric analysis of covariance for comparing change in randomized studies with baseline values subject to error. AB - Change from baseline to a follow-up examination can be compared among two or more randomly assigned treatment groups by using analysis of variance on the change scores. However, a generally more sensitive (powerful) test can be performed using analysis of covariance (ANOVA) on the follow-up data with the baseline data as a covariate. This approach is not without potential problems, though. The assumption of ordinary ANCOVA of normally distributed errors is speculative for many variables employed in biomedical research. Furthermore, the baseline values are inevitably random variables and often are measured with error. This report investigates, in this situation, the validity and relative power of the ordinary ANCOVA test and two asymptotically distribution-free alternative tests, one based on the rank transformation and the other based on the normal scores transformation. The procedures are illustrated with data from a clinical trial. Normal and several nonnormal distributions, as well as varying degree of variable error, are studied by Monte Carlo methods. The normal scores test is generally recommended for statistical practice. PMID- 1912260 TI - Effects of exposure misclassification on regression analyses of epidemiologic follow-up study data. AB - In epidemiologic studies, subjects are often misclassified as to their level of exposure. Ignoring this misclassification error in the analysis introduces bias in the estimates of certain parameters and invalidates many hypothesis tests. For situations in which there is misclassification of exposure in a follow-up study with categorical data, we have developed a model that permits consideration of any number of exposure categories and any number of multiple-category covariates. When used with logistic and Poisson regression procedures, this model helps assess the potential for bias when misclassification is ignored. When reliable ancillary information is available, the model can be used to correct for misclassification bias in the estimates produced by these regression procedures. PMID- 1912261 TI - Regression with bivariate grouped data. AB - The problem of accounting for the grouping of continuous, bivariate data in regression analyses is considered. Reasons why grouping must be taken seriously are advanced, and a strategy for accounting for grouping is demonstrated. The specific model asserts that, in the absence of grouping, the data would be bivariate normal. This model is used to adjust estimates of parameters in a regression relating disease severity to a grouped exposure variable, using data on pneumoconiosis in English coal miners (Ashford, 1959, Biometrics 15, 573-581). The choice of computing methods is discussed and likelihood formulas are presented. PMID- 1912262 TI - Disease clustering in time. AB - Tango (1984, Biometrics 40, 15-26) proposed a clustering index for testing for clusters of disease in time. A test based on this clustering index was shown to compare favourably with other statistical tests. In this article we show that Pearson's X2 and its components perform well in testing for clusters of disease in time. The rth of these components identifies a departure from uniformity in moments up to the rth and so helps describe the alternative, if any, to uniformity. PMID- 1912263 TI - The validity of inferences based on incomplete observations in disease state models. AB - In many survival time studies or studies on the progression of a disease, information is often incomplete in the sense that it is known only that a patient has been in certain disease states at several time points. In this paper, conditions concerning the interrelationship between the disease process and the examination scheme (i.e., the pattern of examination times) are derived under which a valid statistical inference is possible. These conditions are confronted with examination schemes that are of practical importance in clinical research. A cancer marker study is used as an example to estimate the magnitude of the potential bias when the conditions derived are violated. PMID- 1912265 TI - A multivariate growth curve model for pregnancy. AB - A model is proposed for consecutive multivariate observations of pregnancy related quantities for a particular mother assuming proportionally with an underlying univariate growth process. Apart from the longitudinal aspect of the multivariate time series, the cross-sectional distribution of growth curves is also discussed. The model is examined as regards problems of estimation and model checking, and the results are applied to data consisting of bivariate time series of symphyseal fundal distances and fetal weight estimates from 91 mothers. We find some evidence in the data on departures from the model. PMID- 1912264 TI - Detection of two-component mixtures of lognormal distributions in grouped, doubly truncated data: analysis of red blood cell volume distributions. AB - We have examined the statistical requirements for the detection of mixtures of two lognormal distributions in doubly truncated data when the sample size is large. The expectation-maximization algorithm was used for parameter estimation. A bootstrap approach was used to test for a mixture of distributions using the likelihood ratio statistic. Analysis of computer simulated mixtures showed that as the ratio of the difference between the means to the minimum standard deviation increases, the power for detection also increases and the accuracy of parameter estimates improves. These procedures were used to examine the distribution of red blood cell volume in blood samples. Each distribution was doubly truncated to eliminate artifactual frequency counts and tested for best fit to a single lognormal distribution or a mixture of two lognormal distributions. A single population was found in samples obtained from 60 healthy individuals. Two subpopulations of cells were detected in 25 of 27 mixtures of blood prepared in vitro. Analyses of mixtures of blood from 40 patients treated for iron-deficiency anemia showed that subpopulations could be detected in all by 6 weeks after onset of treatment. To determine if two-component mixtures could be detected, distributions were examined from untransfused patients with refractory anemia. In two patients with inherited sideroblastic anemia a mixture of microcytic and normocytic cells was found, while in the third patient a single population of microcytic cells was identified. In two family members previously identified as carriers of inherited sideroblastic anemia, mixtures of microcytic and normocytic subpopulations were found. Twenty-five patients with acquired myelodysplastic anemia were examined. A good fit to a mixture of subpopulations containing abnormal microcytic or macrocytic cells was found in two. We have demonstrated that with large sample sizes, mixtures of distributions can be detected even when distributions appear to be unimodal. These statistical techniques provide a means to characterize and quantify alterations in erythrocyte subpopulations in anemia but could also be applied to any set of grouped, doubly truncated data to test for the presence of a mixture of two lognormal distributions. PMID- 1912266 TI - Modeling the effect of dose on the lifetime tumor rate from an animal carcinogenicity experiment. AB - The proportion of tumor-bearing animals in a chronic bioassay is often used as a basis for assessing risk at human exposure levels that are below the experimental range. However, such a crude experimental tumor rate can be biased by dose related differences in the nontumor mortality. To adjust tumor rates for competing mortality, Kodell, Gaylor, and Chen (1986, Biometrics 42, 867-873) propose a standardized tumor rate, calculated separately in each dose group from dose-specific estimates of the tumor prevalence and mortality functions. This paper extends the approach of Kodell et al, by developing a method of modeling the standardized rate as a function of dose. An advantage of this approach is that it leads to estimates that are monotone in dose. In addition, by modeling the lifetime risk as a function of dose directly, it is possible to obtain estimates for the risk at dose levels outside the experimental range, such as for low-dose extrapolation, and estimation of the "tumorigenic dose 50" (TD50). A semiparametric model is developed, as well as the nonparametric alternative of isotonic regression. Simulations are provided to show the relative bias and precision of the two approaches to that of Kodell et al. PMID- 1912267 TI - Constant risk differences in the analysis of animal tumorigenicity data. AB - In a typical tumorigenicity study, most tumors are not observable in live animals and only a single (terminal) sacrifice is performed. This paper proposes a nonparametric, survival-adjusted analysis for these data that focuses on tumor incidence and yet does not require data on cause of death or assumptions about the tumor's lethality. The tumor onset/death process is most naturally characterized in terms of the tumor incidence rate and the death rates for tumor free and tumor-bearing animals. The proposed approach, however, reparameterizes the problem in terms of the incidence rate, the death rate for tumor-free animals, and the difference between the death rates for tumor-free and tumor bearing animals (i.e., the risk difference). The advantage of this alternative formulation is that a full likelihood analysis is possible with as few as one sacrifice time if the risk difference is assumed to be constant with respect to time. Data from the large ED01 study suggest that reasonable results can be obtained under the assumption of constant risk differences. PMID- 1912268 TI - On the choice of times for data analysis in group sequential clinical trials. AB - Planned interim analysis of randomized clinical trials has been implemented for over a decade. While the initial proposal advocated analyzing after equal numbers of patients were evaluated, a later modification by Lan and DeMets (1983, Biometrika 70, 659-663) allowed for more flexible boundaries. Rather than fixing the times of analysis at equal numbers of patients, they fixed the rate at which overall alpha was used up according to a use function alpha * (t) on t in with alpha * (0) = 0 and alpha * (1) = alpha. Here we consider how flexible Lan and DeMets' procedure is. We show that the choice of alpha * (t) for a particular trial affects the permissible analysis times if other desirable properties of the sequence of nominal significance levels are to hold. To overcome the difficulties posed by patterns of late analysis, piecewise linear convex use functions are proposed. PMID- 1912270 TI - The effect of screening on some pretest-posttest test variances. AB - The clinical trial design in which the endpoint is measured both at baseline and at the end of the study is used in a variety of situations. For two-group designs, test such as the t test or analysis of covariance are commonly used to evaluate treatment efficacy. Often such pretest-posttest trials restrict participation to subjects with a baseline measurement of the endpoint in a certain range. A range may define a disease, or it may be thought that subjects with extreme measurements are more responsive to treatment. This paper examines the effect of screening on the analysis of covariance and t-test variances relative to the population (i.e., unscreened) variances. Bivariate normal and bivariate gamma distributions are assumed for the (pretest, posttest) measurements. Because the sample size required to detect a specified difference between treatment and control is proportional to the variance, the results have direct application to setting sample size. PMID- 1912269 TI - Tests of homogeneity for the relative risk in multiply-matched case-control studies. AB - We examine several tests of homogeneity of the odds ratio in the analysis of 2 x 2 tables arising from epidemiologic 1:R matched case-control studies. The T4 and T5 statistics proposed by Liang and Self (1985, Biometrika 72, 353-358) are unable to detect obvious inhomogeneity in two numerical examples and in simulation studies. The null hypothesis is rejected by the chi-square statistic of Ejigou and McHugh (1984, Biometrika 71, 408-411) and by a new proposed method whose significance level must be simulated. PMID- 1912271 TI - Reducing mean squared error in the analysis of stratified epidemiologic studies. AB - Kalish (1990, Biometrics 46, 493-499) proposed an approximately optimal estimator of a common odds ratio for pair-matched case-control studies. His approach is easily extended to general stratified studies. For unmatched stratified studies, the form of the approximately optimal estimator is very simple, and may often correspond to no more than a small correction to the ordinary stratified estimator. PMID- 1912272 TI - Compliance, bias, and power in clinical trials. PMID- 1912273 TI - Case-control studies with cluster sampling. PMID- 1912274 TI - Electroporation of cell membranes. AB - Electric pulses of intensity in kilovolts per centimeter and of duration in microseconds to milliseconds cause a temporary loss of the semipermeability of cell membranes, thus leading to ion leakage, escape of metabolites, and increased uptake by cells of drugs, molecular probes, and DNA. A generally accepted term describing this phenomenon is "electroporation." Other effects of a high intensity electric field on cell membranes include membrane fusions, bleb formation, cell lysis... etc. Electroporation and its related phenomena reflect the basic bioelectrochemistry of cell membranes and are thus important for the study of membrane structure and function. These phenomena also occur in such events as electric injury, electrocution, and cardiac procedures involving electric shocks. Electroporation has found applications in: (a) introduction of plasmids or foreign DNA into living cells for gene transfections, (b) fusion of cells to prepare heterokaryons, hybridoma, hybrid embryos... etc., (c) insertion of proteins into cell membranes, (d) improving drug delivery and hence effectiveness in chemotherapy of cancerous cells, (e) constructing animal model by fusing human cells with animal tissues, (f) activation of membrane transporters and enzymes, and (g) alteration of genetic expression in living cells. A brief review of mechanistic studies of electroporation is given. PMID- 1912275 TI - Diffusion of nystatin in plasma membrane is inhibited by a glass-membrane seal. AB - In perforated patch recording, the pore former nystatin is incorporated into a cell-attached patch, to increase its conductance. The possibility of lateral diffusion of nystatin through the membrane and under the glass-membrane seal was examined by reversing the nystatin gradient. Namely, a cell-attached patch on a cell was examined while placing nystatin into the bath. The reversal potential and current-voltage relationship of single Ca2+ activated K+ channels in the patch were readily changed by varying the K+ concentration in the bath, showing that nystatin was active in the cell membrane outside of the patch. However, the patch itself did not become leaky. The absence of a conductance induced in the patch by the nystatin in the rest of the plasma membrane of the cell suggests that the lateral diffusion of nystatin is inhibited by the glass-membrane seal. PMID- 1912276 TI - Compression of lipid membranes as observed at varying membrane positions. AB - We have measured the microscopic isothermal compressibility of dioleoyl- and dimyristyl-phosphatidylcholine multilayers and bilayers as a function of membrane depth by the pressure dependence of the polarization of a series of anthroyloxy fatty acids. In both systems, within experimental error, the compressibility did not change with membrane depth. The magnitudes of the compressibilities matched those of organic solids and those reported for dipalmitoylphosphatidylcholine multilayers from neutron diffraction measurements (Braganza, L. F., and D. L. Worcester. 1986. Biochemistry, 25:7484-7488). The bilayer compressibility decreased with temperature and this decrease was similar with membrane depth consistent with the isotropic thermal expansion of membranes previously observed (Scarlata, S. 1989. Biophys. J. 55:1215-1223). The vertical compressibility in the z direction is much lower than the horizontal (xy planes) for probes that lie parallel to the hydrocarbon chains which is consistent with an increase in bilayer thickness. The compressibility for probes that lie perpendicular to the hydrocarbon chains is more isotropic due to their limited spatial access to the z plane. PMID- 1912277 TI - Surface charging by large multivalent molecules. Extending the standard Gouy Chapman treatment. AB - Traditionally, Gouy-Chapman theory has been used to calculate the distribution of ions in the diffuse layer next to a charged surface. In recent years, the same theory has found application to adsorption (incorporation, partitioning) of charged peptides, hormones, or drugs at the membrane-water interface. Empirically it has been found that an effective charge, smaller than the physical charge, must often be used in the Gouy-Chapman formula. In addition, the large size of these molecules can be expected to influence their adsorption isotherms. To improve evaluation techniques for such experiments, comparatively simple extensions of the standard Gouy-Chapman formalism have been studied which are based on a discrete charge virial expansion. The model allows for the mobility of charged groups at the interface. It accounts for finite size of the adsorbed macromolecules and for discrete charge effects arising from pair interactions in the interface plane. In contrast to previous discrete charge treatments this model nearly coincides with the Gouy-Chapman formalism in the case where the adsorbing molecules are univalent. Large discrepancies are found for multivalent molecules. This could explain the reduced effective charges needed in the standard Gouy-Chapman treatment. The reduction factor can be predicted. The model is mainly limited to low surface coverage, typical for the adsorption studies in question. PMID- 1912279 TI - Spatial Fourier analysis of video photobleaching measurements. Principles and optimization. AB - The major use of the fluorescence recovery after photobleaching (FRAP) technique is to measure the translational motion of the molecular components in various condensed media. In a conventional laser spot photobleaching experiment, a photomultiplier is used to measure the total brightness levels of the bleached region in the sample, so no spatial information can be directly obtained. In video-FRAP, a series of images after photobleaching is acquired, allowing the spatial character of the recovery to be determined; this permits direct detection of both anisotropic diffusion and flow. To utilize all of the available image data to determine the transport coefficients, a two-dimensional spatial Fourier transform analysis of the images after photobleaching was employed. The change in the transform between two time points reflects the action of diffusion during the interim. An important advantage of this method, which involves taking the ratio of image transforms at different time points, is that it does not require a specific initial condition to be created by laser photobleaching. The ability of the analysis to extract transport coefficients from computer-simulated diffusional recovery is assessed in the presence of increasing amounts of noise. Experimental data analysis from the diffusion of proteins in viscous solutions and from the diffusion of protein receptors on cell surfaces demonstrate the feasibility of the Fourier analysis to obtain transport coefficients from the video FRAP measurement. PMID- 1912278 TI - Molecular charge dominates the inhibition of actomyosin in skinned muscle fibers by SH1 peptides. AB - It is not definitively known whether the highly conserved region of myosin heavy chain around SH1 (Cys 707) is part of the actin-binding site. We tested this possibility by assaying for competitive inhibition of maximum Ca-activated force production of skinned muscle fibers by synthetic peptides which had sequences derived from the SH1 region of myosin. Force was inhibited by a heptapeptide (IRICRKG) with an apparent K0.5 of about 4 mM. Unloaded shortening velocity of fibers, determined by the slack test, and maximum Ca-activated myofibrillar MgATPase activity were also inhibited by this peptide, but both required higher concentrations. We found that other cationic peptides also inhibited force in a manner that depended on the charge of the peptide; increasing the net positive charge of the peptide increased its efficacy. The inhibition was not significantly affected by altering solution ionic strength (100-200 mM). Disulfide bond formation was not involved in the inhibitory mechanism because a peptide with Thr substituted for Cys was inhibitory in the presence or absence of DTT. Our data demonstrate that the net charge was the predominant molecular characteristic correlated with the ability of peptides from this region of myosin heavy chain to inhibit force production. Thus, the hypothesis that the SH1 region of myosin is an essential part of the force-producing interaction with actin during the cross-bridge cycle (Eto, M., R. Suzuki, F. Morita, H. Kuwayama, N. Nishi, and S. Tokura., 1990, J. Biochem. 108:499-504; Keane et al., 1990, Nature (Lond.). 344:265-268) is not supported. PMID- 1912281 TI - Kinetics of the barotropic ripple (P beta')/lamellar liquid crystal (L alpha) phase transition in fully hydrated dimyristoylphosphatidylcholine (DMPC) monitored by time-resolved x-ray diffraction. AB - We present here the first study of the use of a pressure-jump to induce the ripple (P beta')/lamellar liquid crystal (L alpha) phase transition in fully hydrated 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC). The transition was monitored by using time-resolved x-ray diffraction (TRXRD). Applying a pressure jump from atmospheric to 11.3 MPa (1640 psig, 111.6 atm) in 2.5 s induces the L alpha to P beta' phase transition which takes place in two stages. The lamellar repeat spacing initially increases from a value of 66.0 +/- 0.1 A (n = 4) to a maximum value of 70.3 +/- 0.8 A (n = 4) after 10 s and after a further 100-150 s decreases slightly to 68.5 +/- 0.3 A (n = 4). The reverse transition takes place following a pressure jump in 5.5 s from 11.3 MPa to atmospheric pressure. Again, the transition occurs in two stages with the repeat spacing steadily decreasing from an initial value of 68.5 +/- 0.3 A (n = 3) to a minimum value of 66.6 +/- 0.3 A (n = 3) after 50 s and then increasing by approximately 0.5 A over a period of 100 s. The transition temperature increases linearly with pressure up to 14.1 MPa in accordance with the Clapeyron relation, giving a dT/dP value of 0.285 degrees C/MPa (28.5 degrees C/kbar) and an associated volume change of 40 microliters/g. A dynamic compressibility of 0.13 +/- 0.01 A/MPa has been determined for the L alpha phase. This value is compared with the equilibrium compressibilities of bilayer and nonbilayer phases reported in the literature. The results suggest testable mechanisms for the pressure-induced transition involving changes in periodicity, phase hydration, chain order, and orientation. A more complete understanding of the transition mechanism will require improvement in detector spatial resolution and sensitivity, and data on the pressure sensitivity of phase hydration. PMID- 1912280 TI - Near-infrared Fourier transform Raman and conventional Raman studies of calf gamma-crystallins in the lyophilized state and in solution. AB - We present in this report a detailed structural study of calf gamma-crystallins both in the solid state and in solution by the newly developed technique of near infrared (IR) Fourier transform (FT)-Raman spectroscopy as well as by the conventional Raman method. In comparison with conventional laser Raman spectroscopy, the near-IR FT-Raman approach exhibits several attractive features such as fluorescence rejection capability, frequency accuracy, and the FT's multiplex and throughput advantages. These distinct characteristics combined form the basis for the particular suitability of FT-Raman in crystallin structural analysis and elucidation. We have thus obtained evidence in support of the view that native calf gamma-II crystallin does not contain a disulfide bond either in the lyophilized state or in solution. In addition, conventional Raman spectra are examined for all four gamma-crystallin fractions. gamma-S, gamma-II, gamma-III, and gamma-IV, and the results indicate a high degree of structural similarities among them. It is also found that the sulfhydryl groups in all four gamma crystallins are highly resistant to air oxidation and are capable of maintaining their reduced state during isolation in the absence of added reductants or such chelating agents as EDTA. PMID- 1912282 TI - Synchrotron x-ray diffraction studies of the cornea, with implications for stromal hydration. AB - The intermolecular and interfibrillar spacings of collagen in bovine corneal stroma have been measured as a function of tissue hydration. Data were recorded from low- and high-angle x-ray diffraction patterns obtained using a high intensity synchrotron source. The most frequently occurring interfibrillar spacing varied from 34 nm in dry corneas to 76 nm at H = 5 (the hydration, H, is defined as the ratio of the weight of water to the dry weight). The most frequently occurring intermolecular Bragg spacing increased from 1.15 nm (dry) to approximately 1.60 nm at normal hydration (H approximately 3.2) and continued to increase only slowly above normal hydration. Most of the increase in the intermolecular spacing occurred between H = O and H = 1. Over this hydration range the interfibrillar and intermolecular spacings moved in tandem, which suggests that the initial water goes equally within and between the fibrils. Above H = 1 water goes preferentially between the fibrils. The results suggest that, even at normal hydration, water does not fill the interfibrillar space uniformly, and a proportion is located in another space or compartment. In dried then-rehydrated corneas, a larger proportion of the water goes into this other compartment. In both cases, it is possible to postulate a second set or population of fibrils that are more widely and irregularly separated and therefore do not contribute significantly to the diffraction pattern. PMID- 1912283 TI - Effects of physiologically relevant pressures of helium on the structure of cholesterol-containing lipid bilayers. A neutron diffraction study. AB - We have used neutron diffraction to study the effects of helium gas (1-210 atm) on the structure of a lipid bilayer model of neuronal plasma membranes. We have recorded diffraction patterns from hydrated multilayers of dimyristoyl lecithin and 40% (molar) cholesterol to a resolution of approximately 6.5 A and have calculated scattering amplitude density distributions as a function of pressure. We find that there are no significant changes in the scattering density profiles at 95% confidence over the range of pressures investigated, suggesting that the physiological effects of high helium pressure are unlikely to be a consequence of changes in the structures of the lipid bilayer portions of membranes. PMID- 1912284 TI - Spinodal lines and Flory-Huggins free-energies for solutions of human hemoglobins HbS and HbA. AB - Gelation of deoxygenated solutions of sickle-cell human Hemoglobin (HbS) is of high theoretical interest and it has serious pathological consequences. For this reason HbS is probably the most studied protein capable of self-organization. This notwithstanding, the location in the T, c plane of the region of thermodynamic instability of solutions of deoxy-HbS (as bounded by the spinodal line and as distinct from the gelation region) has remained unknown, along with related values of Flory-Huggins enthalpies and entropies. In the present work this information is derived from experiments for the two cases of (deoxy) HbS and of human adult hemoglobin (HbA). Experiments also show critical exponents having mean-field values, which validates a Flory-Huggins approach. Altogether, the present work offers a quantitative understanding of the thermodynamic effects of the genetic HbA----HbS mutation and it opens the way to similar quantitative evaluations of contributions of pH, salts, cosolutes, and single peptides (even for nongelling hemoglobins), and of potential therapeutic strategies. PMID- 1912286 TI - On the extraction of kinetic rate constants from experimental data. PMID- 1912285 TI - Polydispersity and excluded volume effects in sheared DNA fragments. PMID- 1912287 TI - Hydrophobic core of molten-globule state of bovine carbonic anhydrase B. AB - The interaction which stabilizes the intermediate state of the protein folding and/or unfolding is important for understanding the structure formation mechanism of proteins. The partitioning of a hydrophobic fluorescence probe, pyrene, into the core of a 'molten globule' structure of bovine carbonic anhydrase B was measured, revealing a partition coefficient of about 10(4). The result leads to the conclusion that the compact structure of the molten-globule state is formed by the hydrophobic interaction, as detergent micelles are formed by the same interaction. PMID- 1912288 TI - Biophysical studies of the complexes of polyriboguanylic acid with brominated and chlorinated polyribocytidylic acids. AB - Conformation of double-stranded complexes of polyriboguanylic acid with halogenated polyribocytidylic acid [poly(C)] was studied with the aid of differential pulse polarography, terbium fluorescence and circular dichroism spectrometry. It was shown that halogenation at C(5) of cytosine residues in poly(C) disturbed the ordered structure of the double-helical complex. In addition, this halogenation does not improve antiviral activity of the polynucleotide complex studied in the system of vesicular stomatitis virus and the cell culture of chicken embryos. It was concluded that the regularity of the secondary structure of synthetic RNAs might play an important role in the mechanism of biological activity of these biomacromolecules. PMID- 1912289 TI - Mechanism of protein folding. II. Lysozyme and phospholipase. AB - Refolding of hen egg-white lysozyme assuming the formation of secondary structures (alpha-helices and beta-sheets) is carried out by the method presented in the previous paper (N. Saito et al., Proteins; Struct. Funct. Genet. 3 (1988) 199-208). To do this, the hydrophobic interactions between the hydrophobic residues which are located at the key positions for folding and can be identified without the knowledge of the native structure, and the nonbonded interactions between every pair of atoms (except hydrogen) or groups are introduced successively from short- to medium-distance pairs. The search for the energy minimum by these interactions can afford a conformation of especially the mutual arrangements between neighboring secondary structures. When these local structures are accomplished, some of the long-distance amino-acid pairs come close together and then the possible interactions (hydrophobic, nonbonded) are introduced. The three-dimensional structure of lysozyme thus obtained is shown to have locally correct arrangements of the secondary structures, but mutual relations between long-distance parts of the chain are not similar to the native structure. The introduction of disulfide bonds between appropriate cysteine residues is necessary to reach the native structure. The choice of cysteine pairs for disulfide bonding is made by the criterion given in the paper to follow (K. Watanabe, A. Nakamura, Y. Fukuda and N. Saito. Biophys. Chem. 40 (1991) 293). The same treatment is applied to bovine pancreatic phospholipase with 7 disulfide bonds. The formation of the antiparallel beta-structures from neighboring beta strands and the problem of the folding order are also discussed. PMID- 1912290 TI - Mechanism of protein folding. III. Disulfide bonding. AB - It was shown in lysozyme and phospholipase, and generally in proteins with disulfide bonds, that after the formation of secondary structures the hydrophobic interactions between the key pairs responsible for folding tertiary structures bring several cysteine residues close together. Among the possible combination of cysteine residues some definite pairs are realized in the tertiary structure. In the Appendix to this paper an algebraic relation is given which must be satisfied for two cysteine residues to make a disulfide bond. This relation is too strict to be applied to real problems, where the two cysteines come close together, but the distance is still too great to yield a disulfide bond. In this case the two residues can attract each other by disulfide formation potential. A geometrical graphic representation is given for the locus of the H atom of the SH group in the cysteine residue. This looks like a lampshade and provides us with a guide to select the correct choice among cysteine pairs. This method is applied to lysozyme and phospholipase to supplement the discussion of the preceding paper (T. Yoshimura, H. Noguchi, T. Inoue and N. Saito, Biophys. Chem. 40 (1991) 277). PMID- 1912291 TI - A 35Cl and 37Cl NMR study of chloride binding to the erythrocyte anion transport protein. AB - Band 3, the erythrocyte anion transport protein, mediates the one-for-one exchange of bicarbonate and chloride ions across the membrane and consequently plays an important role in respiration. Binding to the protein forms the first step in the translocation of the chloride across the membrane. 35Cl and 37Cl NMR relaxation measurements at various field strengths were used to study chloride binding to the protein in the presence and absence of the transport inhibitor 4,4'-dinitrostilbene-2,2'-disulfonate. Significant differences occurred in the NMR relaxation rates depending on whether the inhibitor was present or not. The results indicate that the rate of chloride association and dissociation at each external binding site occurs on a time scale of less than or equal to 5 microseconds. This implies that the transmembrane flux is not limited by the rate of chloride binding to the external chloride binding site of band 3. The rotational correlation-time of chloride bound to band 3 was found to be greater than 20 ns with a quadrupole coupling constant of approximately 2 MHz. PMID- 1912292 TI - Isolation of urinary 3-methyladenine using immunoaffinity columns prior to determination by low-resolution gas chromatography-mass spectrometry. AB - An ammonium sulfate precipitated immunoglobin G (IgG) fraction from rabbit antiserum, prepared by use of novel haptenic derivatives, was used to make immunoaffinity columns for purification of 3-methyladenine (3-MeAde) from human urine. IgG was covalently bound to protein A-Sepharose, and the resulting affinity gel columns were sufficiently stable for multiple reuse. 3-MeAde (up to 200 ng) was adsorbed at pH 7.4 and, after extensive washing, eluted with 1 M acetic acid. Recovery of 3-MeAde was typically greater than 90%. For gas chromatography-mass spectrometry analysis, deuterium-labeled (d3) 3-MeAde (50 ng per sample) was used as an internal standard. 3-MeAde was determined as the mono tert-butyldimethylsilyl derivative and quantitated by measurement of ions at m/z 206 (3-MeAde-d0) and m/z 209 (3-MeAde-d3). Repeated analyses of a human urine sample show excellent reproducibility of the method. PMID- 1912294 TI - Studies on the in vitro conversion of haloperidol to a potentially neurotoxic pyridinium metabolite. AB - Evidence that partially oxidized piperidine derivatives such as the Parkinsonian inducing agent 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) are biotransformed in a reaction catalyzed by monoamine oxidase B (MAO-B) to neurotoxic pyridinium metabolites led to studies resulting in the identification of the haloperidol-derived pyridinium metabolite in the urine of drug-treated rats. The present in vitro studies examine the metabolic pathway governing this overall four-electron oxidation. Although haloperidol and its 1,2,3,6 tetrahydropyridine dehydration product were not substrates for purified bovine liver MAO-B, both compounds were biotransformed to the pyridinium product by rat liver microsomal preparations. The dependence on NADPH and the inhibition by SKF 525A argue that one or more liver cytochrome P-450 isozymes may catalyze this transformation. Attempts to detect possible metabolic intermediates were not successful. Chemical model studies, however, suggest that the expected intermediary amino enol and dihydropyridinium species may be too unstable to isolate. The possible significance of this pathway with respect to haloperidol induced central nervous system dysfunction is considered. PMID- 1912295 TI - Isolation of S-(bromophenyl)cysteine isomers from liver proteins of bromobenzene treated rats. PMID- 1912293 TI - Characterization of covalently modified deoxyribonucleosides formed from dibenz[a,j]anthracene in primary cultures of mouse keratinocytes. AB - Identification of various deoxyribonucleoside adducts formed in primary cultures of mouse keratinocytes exposed to dibenz[a,j]anthracene (DB[a,j]A) is presented. A preliminary analysis of the DNA adducts formed from 7 methyldibenz[a,j]anthracene (7MeDB[a,j]A) also is presented. Cultures of keratinocytes obtained from dorsal skins of female SENCAR mice were exposed to 0.5 microgram of tritium-labeled hydrocarbons/mL of medium for 24 h. The total DNA binding was 2.23 +/- 0.54 and 5.28 +/- 0.97 pmol of hydrocarbon/mg of DNA for DB[a,j]A and 7MeDB[a,j]A, respectively. These binding values represented the radioactivity associated with the modified deoxyribonucleosides separated from the normal deoxyribonucleosides on Sephadex LH-20 columns following enzymatic digestion of isolated DNA. Treatment of keratinocytes with DB[a,j]A produced adduct peaks corresponding to marker adducts derived from trans addition of both deoxyguanosine as well as deoxyadenosine residues to the (+) enantiomer of the anti-diol epoxide where the deoxyadenosine adducts were predominant. In addition, DNA adduct peaks corresponding to markers of trans and cis addition, respectively, of deoxyguanosine and deoxyadenosine to the (+)-syn-diol epoxide were also noted in these chromatograms. A major DNA adduct in cells exposed to DB[a,j]A was tentatively identified as resulting from the addition of deoxyadenosine to DB[a,j]A-5,6-oxide. Several other later eluting DNA adduct peaks, not corresponding to any of the marker adducts, were also present in these chromatograms. In comparison, when cells were exposed to the more biologically potent 7-methyl analogue, at least 12 DNA adduct peaks were consistently observed in HPLC chromatograms.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1912296 TI - Redox chemistry of anthracycline antitumor drugs and use of captodative radicals as tools for its elucidation and control. AB - The oxomorpholinyl radicals are unique materials in organic and medicinal chemistry. Their closest parallel lies in inorganic chemistry with dithionite, which exists in equilibrium with sulfur dioxide radical anion, also a one electron reducing agent. However, dithionite is a more powerful reducing agent and is probably more toxic. The rate of release of the oxomorpholinyl radical from its dimer is medium and is structure dependent, which provides for some level of control. The oxomorpholinyl radicals TM-3 and DHM-3 are selective one electron reducing agents for the anthracyclines, generating sequentially semiquinone and hydroquinone redox states. Formation of the reduced states of the anthracyclines is probably relevant to their cytotoxic activity. Semiquinones and hydroquinones react rapidly with molecular oxygen to yield superoxide. Hydroquinone redox states with anaerobic conditions in protic media at pH 7-8 undergo glycosidic cleavage to form quinone methides; in aprotic media or at pH less than 4, they tautomerize to leuco forms. Quinone methides react with protons from solvent to form 7-deoxyaglycons, with some nucleophiles to form adducts, and with molecular oxygen to form semiquinone methide. The reactivity of the quinone methide is a function of substitution; nucleophilic addition is facilitated by the absence of a hydroxyl group at the 11-position and by proper location of the nucleophile. Quinone methides and semiquinone methides are both viable transients for covalently linking anthracycline aglycons to biological macromolecules. DHM-3 dimer is of possible pharmaceutical value for the detoxification of quinone antitumor drugs and for the improvement of chemotherapy through modulating the redox chemistry of the quinone antitumor drugs. PMID- 1912298 TI - Effect on mutagenicity of the stepwise removal of hydroxyl group and chlorine atoms from 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone: 13C NMR chemical shifts as determinants of mutagenicity. AB - The response of mutagenicity to the stepwise replacement of chlorine atoms and the hydroxyl group by hydrogen in 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H) furanone (MX, 1) was determined in several assays by using Salmonella typhimurium tester strain (TA100). In all, eight MX derivatives were assayed. Several were studied together in at least one assay. In addition to MX, the seven included 3 chloro-4-(dichloromethyl)-2(5H)-furanone (RMX, 2), 3-chloro-4-(chloromethyl)-5 hydroxy-2(5H)-furanone (3), 3-chloro-4-(chloromethyl)-2(5H)-furanone (4), 4 (chloromethyl)-5-hydroxy-2(5H)-furanone (5), 4-chloromethyl-2(5H)-furanone (6), and 4-(dichloromethyl)-2(5H)-furanone (8). Compounds 1-6 were mutagenic. Compound 8 gave erratic results. 4-(Acetoxymethyl)-2(5H)-furanone (11) was nonmutagenic. The largest drop in mutagenicity amounted to a factor of about 10(2) for the replacement of the hydroxyl group or a C-3 chlorine atom from 3. Other replacements of the hydroxyl group or a C-3 or C-6 chlorine atom amounted to mutagenicity diminished by a factor of only 10. On the basis of the rates of UV spectral changes under assay conditions, chemical half-life values (ct 1/2) for 1 6 and 8 were estimated as indicators of compound stability. However, mutagenicity differences were shown to result principally from the intrinsic mutagenicities of the six compounds 1-6 rather than from differences in stability.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1912297 TI - Chirality, charge, and chain branching effects on dithiocarbamate-induced mobilization of cadmium from intracellular deposits in mice. AB - The effects of three major structural features on the intracellular cadmium mobilizing potency of dithiocarbamates have been examined. These features, the chirality of the groups, the total ionic charge of the chelating agent, and the extent of chain branching, would be expected to affect the pharmacological properties of these chelating agents but to have little effect on the stability constants of the cadmium complexes involved. A total of 25 compounds (including 21 new ones) was prepared and used in animal studies designed to evaluate these effects. These included a series of amphipathic dithiocarbamates of the general type R1N(R2)CS2-Na+, where R1 is a relatively nonpolar organic group and R2 is derived from a reducing hexose. All of the factors examined influenced the potency of dithiocarbamates in the mobilization of cadmium from intracellular deposits. The compounds with R2 = galactose or mannose and R1 = benzyl were both more effective than the corresponding glucose derivatives in inducing the removal of cadmium from the liver and the whole body. Increases in the net negative charge of the chelating agent uniformly decreased the observed potency in the mobilization of hepatic and renal cadmium deposits. The replacement of a normal alkyl group by a branched-chain group of the same molecular weight also led to an increase in potency for the two pairs of compounds examined. Dithiocarbamates which are not amphipathic because of the presence of similar polar substituents for both R1 and R2, such as sodium diarabitylamine carbodithioate, were relatively ineffective as agents for the mobilization of intracellular cadmium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1912299 TI - Species specificity in the chemical mechanisms of organophosphorus anticholinesterase activity. AB - Structure-activity relationships reveal that the two principal determinants of anticholinesterase activity for various organophosphorus insecticides are steric hindrance and the electrophilic strength of the phosphorus atom. The objective of the present investigation was to distinguish between the molecular properties governing species-related differences in organophosphorus sensitivity by comparing the physical-chemical relationships for the inhibition of brain acetylcholinesterase isolated from rats, chickens, or rainbow trout. A homologous series of five dialkyl p-nitrophenyl phosphates consisting of methyl through n butyl and isopropyl were synthesized and characterized both chemically and biologically. Structure-activity correlations revealed that whereas steric hindrance is the principal factor governing inhibitory potency for rats and hens, the electrophilicity of the phosphorus atom is the principal determinant of anticholinesterase activity in trout. The inductive effect of successive methylene substitutions on the phosphoryl group is reflected by 13C and 31P NMR spectroscopy which correlates with anticholinesterase activity in trout, but not in rats or hens. The results provide the first indication for species-related differences in the molecular regulation of anticholinesterase activity, suggesting that the trout enzyme possesses a relatively weak nucleophilic center within a dimensionally restricted esteratic subsite. Species-specific distinctions in the molecular properties governing anticholinesterase activity provide novel design strategies for improving the selectivity of toxic organophosphorus insecticides. PMID- 1912300 TI - Identification and characterization of deoxyguanosine adducts of methyl vinyl ketone and ethyl vinyl ketone. Genotoxicity of the ketones in the SOS Chromotest. AB - The reaction of the alpha, beta-unsaturated ketones methyl vinyl ketone (MVK) and ethyl vinyl ketone (EVK) with nucleosides and 5'-mononucleotides was studied. The genotoxic activity of MVK and EVK in the SOS Chromotest was investigated. Three different types of adducts with deoxyguanosine were found and their structures elucidated: the cyclic 1,N2 adducts, the linear N7 adducts with one still unreacted carbonyl function, and the cyclic 1,N2, linear N7, bis adducts. The spectroscopic and other relevant characterization data for the deoxyguanosine adducts and the corresponding guanine adducts are presented here together with details of the chromatographic methods used for isolation. The adducts described could also be isolated in the reactions of MVK and EVK with 2'-deoxyguanosine 5' monophosphate. No adducts could be isolated either with nucleosides other than deoxyguanosine or with nucleotides other than 2'-deoxyguanosine 5'-monophosphate, indicating that the guanine moiety is the most reactive DNA constituent for MVK and EVK. MVK and EVK were clearly genotoxic in the SOS Chromotest according to the criteria of Quillardet and Hofnung. The formation of these adducts was proposed as the mechanism for the genotoxicity of MVK and EVK: all data available support the assumption that MVK and EVK represent a mutagenic and carcinogenic risk for mankind. PMID- 1912301 TI - Comparative laser spectroscopic study of DNA and polynucleotide adducts from the (+)-anti-diol epoxide of benzo[a]pyrene. AB - A recently developed methodology [Jankowiak, R., Lu, P., Small, G. J., and Geacintov, N. E. (1990) Chem. Res. Toxicol. 3, 39-46], which combines fluorescence line narrowing spectroscopy at 4.2 K with non-line-narrowed (S2--- S0 laser excitation) fluorescence spectroscopy at 77 K and fluorescence quenching, is used to characterize adducts formed from (+)-anti-BPDE and the alternating copolymers poly(dG-dC).poly(dG-dC) and poly(dA-dT).poly(dA-dT), the nonalternating poly (dG).poly(dC), single-strand poly(dG), and the oligonucleotide d(ATATGTATA). Detailed comparisons of the fluorescence spectra and quenching (with acrylamide) of the properties of the adducts with those of (+)-anti-BPDE-DNA adducts are made. Fluorescence spectra of the trans and cis isomers of the adduct formed from guanosine monophosphate and the adducts of d(ATATGTATA) are used to assign the stereochemistry of the two major DNA adducts as trans-N2-dG moieties which occupy two different DNA sites. Evidence for the existence of minor cis-type guanine adducts is provided. Finally, a fourth type of DNA adduct (minor) is identified and assigned as trans-N6-dA. PMID- 1912302 TI - Comparative studies of N-hydroxylation and N-demethylation by microsomal cytochrome P-450. AB - The N-hydroxylation of representative aromatic amines by rabbit liver microsomes was mediated by cytochrome P-450 as demonstrated by the sensitivity to carbon monoxide and other cytochrome P-450 inhibitors. The rate of N-hydroxylation was increased by induction with phenobarbital. Involvement of isozyme LM2 (P-50IIB1) was demonstrated in reconstituted systems. Aromatic N-hydroxylation was substantially faster and more efficient than aliphatic N-hydroxylation, while N demethylation of aromatic and aliphatic dimethylamines was comparable in rate and efficiency. Aliphatic N-hydroxylation showed no rate increase with increasing pH despite the predicted increase in the concentration of the neutral substrate. The relative rates of N-hydroxylation and N-demethylation were compared for a series of para-substituted aromatic amines. The rate of demethylation of para substituted N,N-dimethylanilines, as measured both by product formation and by NADPH consumption, correlated with the electronic parameter sigma and with the Hansch lipophilicity parameter pi. N-Hydroxylation of a similar series of anilines did not show a dependence on the electronic parameter but was dependent on the lipophilicity parameter. The differing dependence on the electronic parameter suggests that there are different rate-determining processes of N oxidation for these two reactions. PMID- 1912304 TI - A novel application of cyclic voltammetry for direct investigation of metabolic intermediates in microsomal azo reduction. AB - We have established that reduction of azo dyes structurally related to 4 (dimethylamino)-azobenzene (DAB) by rat liver microsomal cytochrome P-450 requires a polar electron-donating substituent on one ring. Reduction of azo dyes containing only electron-donating substituents is insensitive to both oxygen and CO (I substrates). However, reduction of azo dyes containing electron-withdrawing substituents as well is sensitive to both oxygen and CO (S substrates). Positive, irreversible potentials were observed by cyclic voltammetry (CV) in anhydrous solutions for both I and S substrates but not for the nonreducible azo dyes. This positive potential permits electron transfer to dyes from NADPH-cytochrome P-450 reductase and from cytochrome P-450, both of which have negative potentials. Reduction products retaining electron-donating groups (amino, phenolic) also exhibited positive potentials, implying that these groups contribute the positive potential in the dye molecule. All substrates also exhibited two negative potentials with a clear distinction between I and S substrates. The latter exhibited, on average, potentials that were less negative than the former by about 0.6 V. This is consistent with the more rapid reduction of S substrates by liver microsomes [Zbaida and Levine (1990) Biochem. Pharmacol. 40, 2415-2423]. Admitting air to the system quenched the first potential for S but not for I substrates, which is consistent with the oxygen sensitivities of their reduction. Addition of water significantly shifted the second negative potential to a more positive value, ultimately leading to single negative potential. The water permits rapid protonation of the two-electron-reduced intermediate, facilitating further reduction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1912303 TI - DNA methylation in various rat tissues by the esophageal carcinogen N nitrosomethyl-n-amylamine and six of its positional isomers. AB - The major pathway for the bioactivation of asymmetric N-nitrosomethylalkylamines involves cytochrome P-450 catalyzed alpha-C hydroxylation of the alkyl moiety opposite the methyl group, leading to the formation of a methanediazonium ion as the ultimate carcinogen. In the present study we have investigated the effect of the steric configuration of the pentyl chain on the bioactivation of N nitrosomethylpentylamines in vivo. N-Nitrosomethyl-n-amylamine, a potent esophageal carcinogen, and six of its positional isomers were synthesized by nitrosation of the precursor amines. Overall yields and proportions of the respective Z- and E-isomers reflected the steric hindrance at the alpha-carbon of the pentyl groups. The extent of DNA methylation in various rat tissues after a single dose (0.1 mmol/kg; 6-h survival) of the isomers was determined by cation exchange HPLC with fluorescence detection. (1) Among extrahepatic tissues, methylpurine concentrations were highest in esophagus, followed by the nasal and tracheal mucosa and lung. In these tissues, which are phylogenetically derived from the rat ventral entoderm, the relative extent of DNA methylation followed the same pattern for all isomers. (2) In the esophagus, formation of O6 methylguanine (O6-meG) was observed only for isomers with an unsubstituted alpha methylene in the pentyl moiety, i.e., N-nitrosomethylisoamylamine, -n-amylamine, (2-methylbutyl)amine, and -(2,2-dimethylpropyl)amine. (3) In trachea, methylated purines were also detectable after administration of the alpha-substituted isomer, N-nitrosomethyl(1-methylbutyl)amine. (4) Only nasal mucosa and lung were capable of bioactivating N-nitrosomethyl(1,2-dimethylpropyl)amine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1912305 TI - Peroxyl radical trapping and autoxidation reactions of alpha-tocopherol in lipid bilayers. AB - A phospholipid liposome system was employed to model peroxyl radical trapping reactions of alpha-tocopherol (1) in biological membranes. Peroxyl radicals generated by thermolysis of 2,2'-azobis(2,4-dimethylvaleronitrile) (AMVN) at 37 degrees C oxidized 1 to 8a-[(2,4-dimethyl-1-nitrilopent-2-yl)dioxy]tocopherone (3a), 8a-(hydroperoxy)tocopherone (3b), alpha-tocopherol quinone (4), 4a,5-epoxy 8a-hydroperoxytocopherone (6), 2,3-epoxy-alpha-tocopherol quinone (7), and 5,6 epoxy-alpha-tocopherol quinone (8). The products were purified by high performance liquid chromatography and characterized by UV-vis spectroscopy, mass spectrometry, and cochromatography with authentic standards. Products accumulated in approximately constant proportion as 1 was consumed. Tocopherones 3a/3b decomposed in the bilayer primarily by hydrolyzing to produce 4. Tocopherone decomposition also produced small amounts of epoxides 6-8, apparently by unimolecular tocopherone decomposition rather than by peroxyl radical dependent oxidation, since neither AMVN nor 1 affected the rate of 3a loss or the distribution of products. Epoxides 6-8 appear to be formed primarily by autoxidation reactions that compete with the peroxyl radical trapping reactions that form tocopherone 3a. Epoxide products may thus serve as biochemical markers for irreversible oxidation of 1 by peroxyl radicals in membranes. PMID- 1912306 TI - Reactions of aqueous chlorine in vitro in stomach fluid from the rat: chlorination of tyrosine. AB - Aqueous chlorine reacts with tyrosine to form ring-chlorinated products. Ring substitution occurs at Cl:tyrosine mole ratios greater than 1. Because the nitrogen function of amides is much less reactive than that of amines, the aromatic ring of N-acetyltyrosine is chlorinated at chlorine:substrate mole ratios less than 1. When an aqueous solution of the gastric protein pepsin was chlorinated (37 degrees C, 45 min), tyrosine residues were chlorinated at pH 2 but not at pH 8. The carbohydrate, protein, and chloride concentrations in stomach fluid from fasted rats were determined. When varying concentrations of aqueous chlorine (20-180 mg/L Cl2) were added to the stomach fluid at pH 2, tyrosine residues were mono- and dichlorinated on the aromatic ring. The amount of mono- to dichlorination products varied with the concentration of aqueous chlorine. A mechanism is proposed. The implications for toxicological studies involving chlorinated drinking water are discussed. PMID- 1912307 TI - Fluorescence line narrowing: a high-resolution window on DNA and protein damage from chemical carcinogens. PMID- 1912308 TI - Analysis of site-specific binding of (+/-)-anti-benzo[a]pyrene diol epoxide to restriction fragments of pBR322 DNA via photochemical mapping. AB - The binding sites and relative reactivity of (+/-)-7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene [(+/-)-anti-BPDE] covalently bound to restriction fragments of pBR322 DNA are determined. (+/-) anti-BPDE-modified DNA undergoes a photodissociation at the site of these adducts when irradiated with 355-nm laser light, resulting in a scission of the DNA sugar phosphate backbone producing DNA fragments similar to those of Maxam-Gilbert sequencing reactions. The binding sites of (+/-)-anti-BPDE with each DNA base are determined by sequencing gel analysis of the BPDE-mediated photolysis and laser densitometry of the resulting banding patterns. This technique was used to analyze the binding of (+/-)-anti-BPDE to the 5' and 3' strands of the EcoRI/EcoRV and BamHI/SalI restriction fragments of pBR322 DNA. The reactivity of (+/-)-anti-BPDE to guanine bases within guanine-rich regions of DNA is enhanced by as much as a factor of 17 relative to the least reactive guanines which are flanked by non-guanine bases. The results also show enhanced photocleavage of the backbone corresponding to non-guanine bases in guanine-rich regions. These results suggest either that non-guanine basis in guanine-rich regions are more reactive than identical bases in other regions of the restriction fragment or that photocleavage of the backbone occurs adjacent to a BPDE-modified guanine. The binding profiles of (+/-)-anti-BPDE to pBR322 DNA at a binding density of 0.52 and 0.93 BPDE adduct per strand gave essentially identical binding patterns.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1912310 TI - Inhibition of hepatic microsomal cytochrome P-450 dependent monooxygenation activity by the antioxidant 3-tert-butyl-4-hydroxyanisole. AB - The efficacy of 3-tert-butyl-4-hydroxyanisole (BHA) as a chemopreventive agent against chemically induced cancer or toxicity may involve the direct modulation of cytochrome P-450 dependent monooxygenase function. This hypothesis was investigated by using purified rabbit cytochrome P-450IA2 and P-450IIB4 in a reconstitution system with purified NADPH:cytochrome P-450 oxidoreductase and L alpha-dilauroylphosphatidylcholine. BHA caused a concentration-dependent decrease in cytochrome P-450IIB4 dependent 7-ethoxycoumarin O-deethylation, cyclohexane hydroxylation, and benzphetamine N-demethylation activities (IC50; 28, 75, and 290 microM, respectively) and in cytochrome P-450IA2 dependent 7-ethoxyresorufin O-deethylation and acetanilide para hydroxylation activities (IC50 approximately 225 microM). The inhibition of monooxygenation activity was accompanied by redox cycling due to the tert-butylquinone produced during BHA metabolism, as measured by increased NADPH and oxygen consumption or hydrogen peroxide and superoxide anion production. Glutathione was shown to reverse this redox cycling phenomenon but did not reverse the BHA-dependent inhibition of monooxygenation activity. Using standard steady-state kinetic analyses, BHA was shown to be a mixed-type competitive inhibitor of benzphetamine metabolism by cytochrome P-450IIB4, suggesting that BHA does not simply compete as an alternate substrate for the hemoprotein but must also bind to another catalytically functional form of cytochrome P-450. BHA was shown to bind as a ligand to both purified and microsomal cytochrome P-450IA2, resulting in a low to high (type I) spin-state perturbation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1912309 TI - Mapping of (+/-)-anti-benzo[a]pyrene diol epoxide adducts to human c-Ha-ras1 protooncogene. AB - The relative reactivity of the chemical carcinogen (+/-)-7 beta,8 alpha-dihydroxy 9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene [(+/-)-anti-BPDE] to the guanine bases of the first two coding exons of the human c-Ha-ras1 protooncogene is determined to test if (+/-)-anti-BPDE reactivity is correlated with mutations reported for human c-Ha-ras1 protooncogene activation. Plasmid DNA containing the sequence for the human c-Ha-ras1 gene is modified with (+/-)-anti-BPDE to provide approximately 1 covalent adduct per 250 bp. High-resolution mapping of the covalent adducts is achieved by laser-induced photolysis of 32P-labeled restriction fragments of the BPDE-modified plasmid DNA. The (+/-)-anti-BPDE binding profiles to exons 1 and 2 of the human c-Ha-ras1 protooncogene show enhanced reactivity to guanine-rich regions. The guanine bases of oncogene activating codons 12 (GGC) and 13 (GGT) are 5 times more reactive than the least reactive guanine analyzed within this region of the gene. The guanine base of oncogene-activating codon 61 (CAG) exhibits intermediate reactivity relative to the guanines analyzed within this region of the gene. Although preferential chemical reactivity plays a role in the activation of the c-Ha-ras1 protooncogene, the in vivo activation of the c-Ha-ras1 protooncogene by (+/-) anti-BPDE is a complex process, with other important factors involved in the chemically induced activation. PMID- 1912311 TI - Peroxyl radical oxidation of beta-carotene: formation of beta-carotene epoxides. AB - A chemical model system was used to study peroxyl radical trapping reactions of beta-carotene (1) that may contribute to its antioxidant action in biological systems. Peroxyl radicals generated in hexane by thermolysis of azobis(2,4 dimethylvaleronitrile) (AMVN) at 37 degrees C oxidized 1 to 5,6-epoxy-beta,beta carotene (2) and a previously unreported product, 15,15'-epoxy-beta,beta-carotene (6), in addition to several unidentified polar products. The epoxide products were purified by high-performance liquid chromatography and characterized by UV vis spectroscopy, mass spectrometry, and 1H NMR. Epoxides 2 and 6 and the polar products were formed together from the initial stages of the reaction. As the reaction progressed, the epoxides were oxidized further to more polar products. Although epoxides 2 and 6 were formed at similar rates, 2 was oxidized more rapidly than 6. Incubations with [14C]-1 indicate that at their maximum concentrations 2 and 6 account for approximately 20% of the radiolabeled oxidation products. Epoxide formation may result from peroxyl radical addition to the polyene chain to form a resonance-stabilized peroxyl radical adduct. Peroxide bond scission would yield the epoxide and release an alkoxyl radical. Although this two-step sequence produces no net radical trapping, it could produce a kinetically significant inhibition of peroxyl radical propagation and account, in part, for the antioxidant properties of 1. Epoxides 2 and 6 are structurally distinct from retinoids, which are the metabolic products of 1, and therefore may be useful biochemical markers for its antioxidant actions. PMID- 1912312 TI - Activation energies and formation rate constants for organic arsenical-antidote adducts as determined by dynamic NMR spectroscopy. AB - Phenyldichloroarsine reacts with 1,3-dimercapto-2-propanol and 1,2 dimercaptopropane to form 1:1 adducts in the form of a six-membered and five membered heteroatom rings. Two geometric isomers for each compound are present in dynamic equilibrium. Rate constants and the activation barriers for the interconversion of the geometric isomers were determined by dynamic NMR spectroscopy. The activation barriers indicate that the five-membered heteroatom ring is more stable than the six-membered heteroatom ring. PMID- 1912313 TI - Spectroscopic characterization of syn-5-methylchrysene 1,2-dihydrodiol 3,4 epoxide-deoxyribonucleoside adducts. AB - Eight deoxyribonucleoside adducts formed from reactions of syn-5-methylchrysene 1,2-dihydrodiol 3,4-epoxide with DNA or with nucleotides were characterized spectroscopically. The adducts arose from both cis and trans opening of the epoxide ring at C4 by the amino group of either deoxyadenosine or deoxyguanosine residues. NMR data indicated that the partially saturated 1,2,3,4-ring of the hydrocarbon residue adopted a boatlike conformation, with the purine residue being disposed pseudoaxially in all adducts. The cis and trans assignments for epoxide ring opening were readily made from coupling constants. Quantitatively, cis adducts predominated over trans adducts in both DNA and nucleotide reactions. Whereas deoxyadenylic acid appeared to trap this dihydrodiol epoxide more efficiently than deoxyguanylic acid, reaction with DNA led to more extensive reaction with deoxyguanosine than with deoxyadenosine residues. PMID- 1912315 TI - An unusual dearomatized adduct formed by reaction of 4'-fluoro-4 (acetylamino)biphenyl N-sulfate with deoxyadenosine. AB - The sulfate ester of the liver carcinogen N-hydroxy-4'-fluoro-4 (acetylamino)biphenyl (FAABP-N-sulfate) is believed to be a reactive intermediate in the male rat liver in vivo. After reaction of FAABP-N-sulfate with double stranded calf thymus DNA in vitro, 30% of the adducts was identified as N (deoxyguanosin-8-yl)-4'-fluoro-4-(acetylamino)biphenyl(dG-C8- FAABP) and 16% was suggested to be 3-(deoxyguanosin-N2-yl)-4'-fluoro-4-(acetylamino)biphenyl. To investigate the identity of the remaining adducts, FAABP-N-sulfate was reacted with deoxyadenosine. Two adducts could be isolated, which were identified by 1H NMR and mass spectrometry as 3-(deoxyadenosin-N6-yl)-4'-fluoro-4 (acetylamino)biphenyl (3-dA-N6-FAABP) and -(deoxyadenosin-N6-yl)-4'-fluoro-4 (acetylimino)-3, 4-dihydrobiphenyl (3-dA-N6-FHAIBP). An additional center of chirality is introduced at C3 (biphenyl) in the latter adduct. Therefore, 3-dA-N6 FHAIPB exists as a pair of two diastereomers with H-3 (biphenyl) in the alpha or beta position. Hydrogen bonding between the proton on N6 (adenine) and the imine nitrogen or the acetylimino oxygen is suggested to stabilize 3-dA-N6-FHAIBP and to prevent its conversion to 3-dA-N6-FAABP by restoration of the aromatic system. The adduct 3-dA-N6-FHAIBP was also formed in the reaction of N-OSO3H-FAABP with DNA; it accounted for 3-6% of total covalent binding. PMID- 1912314 TI - Dependence of conformations of benzo[a]pyrene diol epoxide-DNA adducts derived from stereoisomers of different tumorigenicities on base sequence. AB - The conformations of covalent adducts derived from the binding of the highly tumorigenic stereoisomer (+)-trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10 tetrahydrobenzo[a]pyren e [(+)-anti-BPDE] and its nontumorigenic (-)-anti-BPDE isomer with poly[(dG).(dC)], poly[(dG-dC).(dG-dC)], poly[(dT-dC).(dG-dA)], and poly[(dA-dC).(dG-dT)] were investigated by employing UV absorbance and linear dichroism methods. The degrees of orientation of the BPDE residues (bound covalently to N2 of deoxyguanosine), relative to the DNA bases, are most pronounced in the alternating and nonalternating (dG).(dC) polymers and decrease in polymers with neighboring dA.dT base pairs. The tumorigenic (+)-anti-BPDE isomer gives rise predominantly to external (solvent-exposed) site II adducts, while the (-)-enantiomer gives rise predominantly to site I adducts with significant carcinogen-nucleoside interactions. In the mixed (dA-dC).(dG-dT) and (dT-dC).(dG-dA) copolymers, the (+)-anti-BPDE isomer also binds predominantly to N2 of deoxyguanosine, but the adducts are weakly oriented with respect to the DNA bases. The incidence of site II adducts is considerably reduced as compared to the (dG).(dC) and (dG-dC).(dG-dC) polymers, and there is a greater proportion of site I adducts; the presence of a significant proportion of unordered adduct forms is also suggested from the diffuseness and broadness of the absorption spectra in the dA.dT base pair containing polymers. The preference of formation of site II adducts in dG-rich sequences in the case of the biologically highly active (+)-anti-BPDE isomer is discussed in terms of the known binding and mutation spectra. PMID- 1912316 TI - Application of ELISA techniques to metabolic disposition studies for 1,3 dinitrobenzene: comparison with HPLC and radiochemical methods. AB - An enzyme-linked immunosorbent assay (ELISA) is reported for the detection and quantitation of 1,3-dinitrobenzene, a widely used chemical intermediate in industrial syntheses and potent testicular toxicant in rats. Radiolabeled [14C] 1,3-dinitrobenzene (25 mg/kg, ip) was administered to rats, and the blood disappearance curve generated with the ELISA assay was compared with HPLC separation and quantitation by using both UV and radiochemical methods. An excellent correlation was found between the two methods. Matrix effects from the blood samples were minimal. Cross reactivity with metabolites of 1,3 dinitrobenzene occurred only at levels that were 3 orders of magnitude greater than for the parent compound. The specificity of the ELISA for 1,3-dinitrobenzene was further demonstrated with a variety of other nitroaromatic compounds, of which only 2,4-dinitrotoluene showed significant cross reactivity. The sensitivity and specificity of the 1,3-dinitrobenzene ELISA demonstrate the usefulness of an approach which, if verified with conventional analytical methods, allows rapid and inexpensive measurement of xenobiotic levels in biological samples. PMID- 1912317 TI - 1,3-Dialkyltriazenes: reactive intermediates and DNA alkylation. AB - The reactions of calf thymus (ct) DNA with 1,3-dimethyltriazene (DMT), N-methyl-N nitrosourea (MNU), 1,3-diethyltriazene (DET), N-ethyl-N-nitrosourea (ENU), and 1 ethyl-3-methyltriazene (MET) were studied as a function of concentration of the alkylating agents, of various buffers, and of ionic strength. The amount of alkylation at the 7- and O6-positions of guanine increased linearly with dose over a 10-fold concentration range. The slopes of the DMT and MNU curves were identical as were those of DET and ENU. These data suggest that both types of compounds alkylate DNA via a similar intermediate, presumably the corresponding alkanediazonium ion. MET methylates and ethylates DNA, the amount of each product being a function of the competitive formation of the two diazonium ions possible from MET. The MET product ratios could be reproduced by an appropriate mixture of DET and DMT. The alkylation of DNA by DMT and by MET is very sensitive to ionic strength, to the nature of the buffer, and to the identity of the salt used to balance ionic strength. In general, the reaction is favored by low ionic strength, by amine rather than oxy acid buffers, and by doubly charged inert anions. The alkylation of DNA is inversely proportional to the logarithm of the ionic strength over a wide range. The mutagenic activity of triazenes in Salmonella typhimurium is correlated very well with the ability of the triazenes to form adducts, particularly O6-guanine adducts.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1912318 TI - The ozonation of unsaturated fatty acids: aldehydes and hydrogen peroxide as products and possible mediators of ozone toxicity. AB - The products of the reactions of ozone with aqueous emulsions of unsaturated fatty acids and with liposomes made from phosphatidylcholine esters were characterized. Ozonolysis of emulsions of methyl oleate yields approximately 1 mol of hydrogen peroxide and 2 mol of aldehydes per mole of ozone used and fatty acid reacted. That is, the net equation that occurs is RCH = CHR' + O3 + H2O--- RCHO + R'CHO + H2O2 . Ozonolysis of emulsions of oleic, linoleic, linolenic, and arachidonic acids gives 1 mol of hydrogen peroxide per mole of ozone used. Only very low yields (less than 5%) of reducible materials other than hydrogen peroxide are observed, suggesting that the yields of organic peroxidic materials, including Criegee ozonides and lipid hydroperoxides, are small. Ozonolysis of rat erythrocyte ghost membranes and rat bronchoalveolar lavage also gives significant yields (about 50%) of hydrogen peroxide based on the moles of ozone consumed. Reactions of ozone with bovine serum albumin, glutathione, and glucose do not produce hydrogen peroxide, implying that the hydrogen peroxide formed during the ozonation of biological materials arises almost exclusively from ozone/olefin reactions. Hydrogen peroxide and aldehydes are suggested to be important mediators of the modifications observed in both the lung and extrapulmonary tissues when ozone is inhaled. PMID- 1912319 TI - Identification of epoxide- and quinone-derived bromobenzene adducts to protein sulfur nucleophiles. AB - Bromobenzene (BB) hepatotoxicity is widely attributed to the alkylation of cellular proteins by chemically reactive metabolites, particularly BB-3,4-oxide. This laboratory recently reported the first conclusive evidence that BB epoxides actually do alkylate proteins; i.e., acid hydrolysates of hepatic proteins from phenobarbital-(PB-) induced BB-treated rats contain S-(o-, S-(m-, and S-(p bromophenyl)cysteine [Weller, P.E., and Hanzlik, R.P. (1991) Chem. Res. Toxicol. 4, 17-20]. However, these three compounds account for less than 0.5% of total protein covalent binding. Bromoquinone metabolites of BB are also suspected of alkylating proteins. To search for such adducts to protein cysteinyl or methionyl residues, we heated hepatic proteins from PB-induced BB-treated rats with a two phase mixture of 16 N KOH and CH3I ("alkaline permethylation"). Under these conditions S-alkylated residues are cleaved via elimination and the phenoxide and thiophenoxide groups on the fragments are methylated. Product analysis by 14C HPLC and GC/MS revealed o-, m-, and p-bromothioanisoles in amounts comparable to the content of S-(bromophenyl)cysteines found by acid hydrolysis (para much greater than meta, ortho). This, too, clearly implicates protein-SH alkylation by BB-2,3- and 3,4-oxides. In addition, 2,3-dimethoxy-5-bromothioanisole and another unidentified isomer were observed. However, by far the major adduct (5-6% of total covalent binding) was 2,5-dimethoxythioanisole (i.e., a debrominated adduct). When BB-d5 was administered, the latter contained mostly 3 deuterium atoms/mol. These latter results clearly show that alkylation of protein sulfur nucleophiles in vivo by quinone metabolites is 10-15 times more extensive than their alkylation by BB epoxides. After BB-d5 was administered, the bromothioanisoles and dimethoxybromothioanisoles contained 4 and 2 deuterium atoms/mol, respectively. A weighted average calculation of deuterium retention across the six major sulfur adducts agreed well with 3H/14C retention ratios determined earlier for total liver protein covalent binding of dual-labeled [3H/14C]BB, indicating that the overall pattern of BB metabolite binding to all protein nucleophiles may closely parallel that seen here specifically for protein sulfhydryl groups. The identification of a variety of specific BB-derived adducts to protein now affords the opportunity to investigate their relative contributions to the toxicity of bromobenzene. PMID- 1912320 TI - Conversion of a hemoglobin alpha chain aspartate(47) ester to N-(2,3 dihydroxypropyl)asparagine as a method for identification of the principal binding site for benzo[a]pyrene anti-diol epoxide. AB - Human hemoglobin was alkylated with (+/-)-7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE) and then treated with aqueous (+/-)-3-amino-1,2-propanediol to convert alkylated carboxyl side chains to N-(2,3-dihydroxypropyl) amides. Tryptic peptides produced from the modified protein were subjected to affinity chromatography on phenylboronic acid. The bound fraction was further purified by HPLC on C-4 reverse-phase medium to yield one modified peptide, which was identified as the Thr(41)-Lys(56) peptide of the alpha chain by amino acid analysis, Edman sequencing analysis, and FAB-MS. Limited direct evidence from this study and further indirect evidence from previous work identify Asp(47) alpha as the amino acid reacting with BPDE. The only other likely sites would be the C-terminal carboxyl groups of either the alpha or beta chain. Possible reasons for the site selectivity of the alkylation of human hemoglobin by BPDE are discussed. PMID- 1912321 TI - Mass spectrometric analysis of tobacco-specific nitrosamine-DNA adducts in smokers and nonsmokers. AB - A gas chromatography, negative ion chemical ionization mass spectrometry (GC-NICI MS) based assay for tobacco-specific nitrosamine adducts of DNA is described. The assay is based on the observation that acid hydrolysis of DNA from animals treated with tobacco-specific nitrosamines releases 4-hydroxy-1-(3-pyridyl)-1 butanone (HPB). HPB and the internal standard [4,4-D2]HPB are derivatized with pentafluorobenzoyl chloride and the resulting HPB-pentafluorobenzoate is purified by high-performance liquid chromatography prior to GC-NICI-MS analysis. DNA from human peripheral lung and tracheobronchial tissue, collected at autopsy, was analyzed for acid-released HPB. The mean HPB level (fmol/mg of DNA) for peripheral lung DNA was 11 +/- 16 (SD, n = 9) for smokers and 0.9 +/- 2.3 (n = 8) for nonsmokers. Mean adduct levels in tracheobronchus were 16 +/- 18 (n = 4) for smokers and 0.9 +/- 1.7 (n = 4) for nonsmokers. These are the first measurements of tobacco-specific nitrosamine-DNA adducts in humans. Further studies comparing the levels of DNA and globin adducts will provide a better understanding of the metabolic activation of tobacco-specific nitrosamines in humans and may provide a more accurate indication of an individual's risk of developing tobacco-related cancer. PMID- 1912322 TI - Theoretical structure-activity study of mutagenic allyl chlorides. AB - Ab initio molecular orbital calculations at the STO-3G and 3-21G levels were used to clarify the mechanism of mutagenic action of various substituted allyl chlorides. Computed molecular properties were compared with experimental mutagenic potentials of these allylic compounds. In agreement with experiment, the computational results suggest that the primary mechanism of action involves the SN1 formation of allylic cations which then react with nucleophilic centers of nucleic acid bases. The usefulness of computed properties in estimating the degree of alkylating activity and mutagenicity was evaluated. In general, stability of the allylic carbocation intermediate and the degree of charge delocalization in the allyl system correlate well with observed mutagenic potentials. PMID- 1912323 TI - Pyrroles as effective agents for blocking amine nitrosation. AB - The ability of 10 pyrroles to block the acidic nitrosation of morpholine has been determined by using an assay that measures their effectiveness in the presence of a 10-fold excess of amine. The log (% N-nitrosomorpholine) formed is a linear function of blocking agent concentrations ranging from 0.0 to 1.5 times the equivalents of initial nitrite. The negative slopes of these plots allow a ranking of the effectiveness of the blocking agent. Several of the pyrroles have been found to be much more effective than established blocking agents such as ascorbic acid. The following order of blocking ability has been determined: 2,5 dimethylpyrrole = 1-benzyl-2,5-dimethylpyrrole much greater than 4-methylcatechol greater than ascorbic acid = 1,2-phenylenediamine = pyrrole greater than 1,2,5 tribenzylpyrrole = 1-benzylpyrrole = octamethylporphine much greater than ammonium sulfamate = hydrazine = 2,5-diphenylpyrrole much much greater than beta nicotyrine greater than 2-pyrrolecarboxylic acid. Pyrroles give complex mixtures devoid of N-nitroso compounds upon nitrosation. PMID- 1912325 TI - Oxidation of toxic and carcinogenic chemicals by human cytochrome P-450 enzymes. PMID- 1912324 TI - Blocking nitrosamine formation with polymers. AB - A set of polymers have been synthesized in order to determine whether polymers containing nitrosation-reactive functional groups could effectively block nitrosamine formation. Polymers containing both hydrophobic backbones [poly[(chloromethyl)styrene], poly(ethylene oxide-co-epichlorohydrin), chloromethylated cross-linked polystyrene] and hydrophilic backbones [poly(ethylenimine) and poly(acryloyl chloride)] have been derivatized with pyrrole, 2,5-dimethylpyrrole, 2-[(methylamino)methyl]pyrrole, or hydroquinone. All of these polymers, as well as PEI itself, are effective at blocking the nitrosation of morpholine by nitrous acid. The hydrophilic polymers are much better able to compete for the available nitrosating agent in aqueous solution than are the hydrophobic polymers. Nevertheless, all of the polymers were highly effective in scavenging nitrous acid from aqueous solution prior to addition of the amine. The reaction products derived from the reactive, polymer-attached functional groups are retained on the polymer and are easily removed from mixtures of chemicals by physical means. Since nitrosamines and other N-nitroso compounds are known to be potent animal carcinogens, this work is of significance in the area of preventive chemical toxicology. PMID- 1912327 TI - Enzymatic oxidation of ethyl carbamate to vinyl carbamate and its role as an intermediate in the formation of 1,N6-ethenoadenosine. AB - The carcinogen ethyl carbamate has been postulated to be activated by oxidation to vinyl carbamate and then to an epoxide which can react with nucleic acids [Dahl, G.A., Miller, J. A., and Miller, E. C. (1978) Cancer Res. 38, 3793-3804]. To date, the enzymatic conversion of ethyl carbamate to vinyl carbamate had not been demonstrated. Recently, we obtained evidence that the same cytochrome P-450 enzyme (P-450 2E1) is involved in the oxidation of both ethyl carbamate and vinyl carbamate [Guengerich, F. P., Kim, D.-H., and Iwasaki, M. (1991) Chem. Res. Toxicol. 4, 168-179]. When human liver microsomes were incubated with NADPH and ethyl carbamate, the products vinyl carbamate, 2-hydroxyethyl carbamate, and ethyl N-hydroxycarbamate were detected by use of (a) combined capillary gas chromatography/chemical ionization mass spectrometry or (b) high-performance liquid chromatography of radioactive materials. A Km of approximately 54 microM was estimated for the conversion of vinyl carbamate to 1,N6-ethenoadenosine (in the presence of adenosine), but when the reaction was done with ethyl carbamate as the substrate, the rate of product formation was nearly first order in ethyl carbamate concentration (Km greater than 2 mM) and the rate was considerably slower than in the case of vinyl carbamate. The model derived with these parameters predicts a steady-state level of 0.22 microM vinyl carbamate, consonant with the value of approximately 0.2 microM estimated experimentally. A large kinetic deuterium isotope effect (greater than 7) was observed for the formation of 1,N6-ethenoadenosine from ethyl carbamate, and high isotope effects (6-8) were also noted for the formation of vinyl carbamate and 2-hydroxyethyl carbamate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1912326 TI - Deuterium isotope effect in the interaction of N-nitrosodimethylamine, ethanol, and related compounds with cytochrome P-450IIE1. AB - Deuteration of N-nitrosodimethylamine (NDMA) decreases its carcinogenicity and produces an isotope effect on its metabolism. Our previous results showed that deuteration causes a 5-fold increase in the apparent Km, but not the Vmax, for the demethylation and denitrosation of NDMA in microsomes. In the present work, we studied the nature of this deuterium isotope effect with several compounds using acetone-induced microsomes as a source of cytochrome P-450IIE1. In the microsomal N-nitrosodiethylamine deethylase reaction, NDMA and [2H6]NDMA were competitive inhibitors and displayed apparent Ki values of 59 and 441 mM, respectively, showing an isotope effect of 0.13. Similarly, in the p-nitrophenol hydroxylase reaction, a deuterium isotope effect of 0.21 on the Ki was observed. With acetone as an inhibitor for p-nitrophenol hydroxylase, the isotope effect on the Ki was 0.11. Similar deuterium isotope effects were also observed with acetone and dimethylformamide as competitive inhibitors for NDMA demethylase. When the oxidation of ethanol, [1,1-2H2]ethanol, [2,2,2-2H3]ethanol, and [2H6]ethanol was compared, an isotope effect of about 5 was found in the Vmax/Km due to the deuteration of the methylene group (carbon 1) but not due to the methyl group. However, the Vmax was not affected. A corresponding deuterium isotope effect was observed in the Ki when these compounds were used as competitive inhibitors for the NDMA demethylase reaction. The results demonstrate that deuteration of NDMA, ethanol, and related compounds results in an increase in the Km or Ki with little change in the Vmax of P-450IIE1-catalyzed reactions. The molecular basis of this isotope effect is discussed. PMID- 1912328 TI - Transformation of dopamine and alpha-methyldopamine by NG108-15 cells: formation of thiol adducts. AB - The catecholamines, alpha-methyldopamine (alpha-MeDA) and dopamine (DA), have been implicated in 3,4-(methylenedioxy)amphetamine (MDA) toxicity. The toxicity and metabolic fate of alpha-MeDA, a metabolite of MDA, and DA, a neurotransmitter released by MDA administration, were examined in NG108-15 cells. Both catechols were found to accumulate intracellularly into NG108-15 cells. alpha-MeDA was about 4 times more toxic than DA in the cells. The depletion of glutathione (GSH) by buthionine sulfoximine (BSO) resulted in a drastic increase (10 times) in the alpha-MeDA mediated toxicity while the toxicity of DA was enhanced by 2 times. DA was largely metabolized to dihydroxyphenylacetic acid (DOPAC) and, to a smaller extent, formed an adduct with GSH. alpha-MeDA was primarily metabolized to a GSH adduct. alpha-MeDA was also metabolized to a product which was identified as the cysteinyl adduct. These adducts were identified by HPLC coelution with authentic standards. The GSH and cysteinyl adducts are presumably formed through conjugation of the thiols with intermediary quinone oxidation products of DA and alpha-MeDA. Previous studies indicate that alpha-MeDA is significantly more toxic than DA, especially under conditions of GSH depletion. The results of this study suggest that alpha-MeDA toxicity may occur through cytoplasmic accumulation and oxidation to a reactive quinone species followed by reaction with vital thiol functions or generation of reactive oxygen species. Cytoplasmic DA levels, on the other hand, appear to be significantly lower due to MAO metabolism and vesicular storage, and therefore, DA appears less likely to form conjugates with thiol groups or participate in possible redox cycling. PMID- 1912329 TI - C-formylation in the presence of rat brain mitochondria of the 2,3,4,5 tetrahydropyridinium metabolite derived from the psychotomimetic drug phencyclidine. AB - The 1-(1-phenylcyclohexyl)-2,3,4,5-tetrahydropyridinium metabolite derived from the psychotomimetic agent phencyclidine [1-(1-phenylcyclohexyl)piperidine] is converted to 1-(phenylcyclohexyl)-1,2,3,4-tetrahydropyridine-5-carboxaldehyde in the presence of rat brain and liver mitochondria. The C-5 formylation of synthetic 1-(1-phenylcyclohexyl)-2,3,4,5-tetrahydropyridinium perchlorate by N5 formyltetrahydrofolic acid (folinic acid) suggests that this biotransformation is mediated by a transformylation process involving this N5- or the corresponding N10-formyltetrahydrofolic acid. PMID- 1912330 TI - Formation, stability, and rearrangements of the glutathione conjugates of butadiene monoxide: evidence for the formation of stable sulfurane intermediates. AB - Butadiene monoxide, a toxic metabolite of 1,3-butadiene, is a substrate for the human placental glutathione (GSH) S-transferase. The products have been identified as S-(2-hydroxy-3-buten-1-yl)glutathione (I) and S-(1-hydroxy-3-buten 2-yl)glutathione (II). S-(4-hydroxy-2-buten-1-yl)glutathione (III), which was formed chemically, was not detected. 1H NMR analysis of II was consistent with its structure, but spectra of I indicated a 1:1 equilibrium between I and the sulfurane tautomer (IVB) formed by intramolecular displacement of the hydroxyl group by the sulfur atom. The ratio of I to IVB did not change whether the spectrum was obtained at pH 3, 7, or 9 in the presence or absence of LiClO4. Incubations of I at pH 7 or 9 for 5 days at 25 degrees C or for 7 h at 50 degrees C, in the presence or absence of nucleophiles plus LiClO4, did not affect the HPLC profile of I. Storage of I at -20 degrees C for 30 weeks, reflux at pH 7.8 for 5 h in the presence of GSH, or incubations at pH 2 for 5 h at 55 degrees C in the presence of GSH or 2-mercaptoethanol, however, resulted in the conversion of I to III (10-30%). Treatment of I with H2O2 resulted in formation of the corresponding sulfoxide (V) and sulfone (VI), which blocked the formation of III. NMR and chemical reactivity studies of III indicated an initial 1:1 equilibrium between III and the five-membered ring sulfurane (VIIB) formed by intramolecular displacement of the hydroxyl group by the sulfur atom.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1912331 TI - Carbamoylation of peptides and proteins in vitro by S-(N methylcarbamoyl)glutathione and S-(N-methylcarbamoyl)cysteine, two electrophilic S-linked conjugates of methyl isocyanate. AB - The reactivity toward peptides and proteins of S-(N-methylcarbamoyl)glutathione (SMG), the glutathione conjugate of methyl isocyanate, and the corresponding cysteine adduct, S-(N-methylcarbamoyl)cysteine (SMC), was investigated with the aid of in vitro model systems. Incubation of SMC or a trideuteriomethyl analogue of SMC with either the reduced or oxidized forms of oxytocin afforded similar mixtures of mono-, bis- and tris-N-methylcarbamoylated peptides. Structure elucidation of the mono and bis adducts by fast atom bombardment tandem mass spectrometry indicated that carbamoylation of oxytocin occurred preferentially at Cys-6 and that Cys-1 and/or Tyr-2 were secondary sites of modification. Upon incubation of S-[N-([14C]methyl)carbamoyl]glutathione (14C-SMG) with native bovine serum albumin (BSA), radioactivity became bound covalently to the protein in a time- and concentration-dependent fashion. "Blocking" of the lone Cys-34 thiol group of BSA in the form of a disulfide prior to exposure of the protein to 14C-SMG failed to decrease significantly the extent or time course of this covalent binding. It is concluded that carbamate thioester conjugates of MIC are reactive, carbamoylating entities which can donate the elements of MIC to nucleophilic functionalities on peptides and proteins. Free thiols appear to be preferred sites for such carbamoylation processes, a phenomenon that may have important toxicological consequences in the pathology of tissue lesions induced by MIC and related isocyanates. PMID- 1912333 TI - Reaction of a chemotherapeutic agent, 6-mercaptopurine, with a direct-acting, electrophilic carcinogen, benzo[a]pyrene-7,8-diol 9,10-epoxide. AB - The chemotherapeutic agent 6-mercaptopurine (6-MP) has been shown to react covalently with the ultimate carcinogenic metabolite of benzo[a]pyrene, 7-r,8-t dihydroxy-9-t,10-t-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE), in aqueous solution, forming a single adduct. NMR studies of the HPLC-purified product were consistent with its identification as 10(S)-(6'-mercaptopurinyl)-7,8,9-trihydroxy 7,8,9,10- tetrahydrobenzo[a]pyrene. Reaction kinetics were analyzed by using both HPLC separation of the products formed and a spectrophotometric assay for adduct formation. A simple model in which direct reaction between 6-MP and BPDE takes place without formation of a physical complex was found to adequately predict the dependence of product ratios on 6-MP concentration. Variations in the observed rate constant for this reaction with changes in temperature, pH, and buffer concentration were determined and compared to the effects of these variables on the observed rate constant for BPDE hydrolysis. In each case, the processes were affected quite differently, suggesting that different rate-determining steps are involved. The data suggest that the reaction mechanism involves SN2 attack of the anion of 6-MP, formed by ionization of the sulfhydryl group, on carbon 10 of BPDE, resulting in a trans-9,10 reaction product. PMID- 1912332 TI - Isolation and characterization of N7-guanyl adducts derived from 1,2-dibromo-3 chloropropane. AB - 1,2-Dibromo-3-chloropropane is a potent renal and testicular toxicant and has been shown to induce tumor formation in laboratory animals. The toxic effects of the compound are thought to be a result of a bioactivation step in which a glutathione conjugate is formed and subsequently reacts with cellular DNA. The L glutathione conjugate of 1,2-dibromo-3-chloropropane was chemically synthesized and used to alkylate DNA: following incubations of the conjugate with calf thymus DNA and neutral thermal hydrolysis (to release N7-guanyl adducts) four major fluorescent products were observed. Three of these were isolated and characterized, the structures being determined as S-[bis(N7 guanylmethyl)methyl]glutathione and the two diastereomers of S-[1-(hydroxymethyl) 2-(N7-guanyl)ethyl]glutathione. The fourth fluorescent product was unstable and formed in low yield and thus could not be characterized. The formation of these N7-guanyl adducts can be explained by a mechanism that includes the formation of two consecutive episulfonium ion intermediates followed by nucleophilic attack at the unsubstituted methylene carbon. These adducts bear structural and mechanistic similarities to the major adduct derived from 1,2-dibromoethane, S-[2-(N7 guanyl)ethyl]glutathione. The same adducts were also formed when DBCP was incubated with rat liver cytosol, GSH, and DNA. In vivo experiments with DBCP yielded very low levels of the N7-guanyl adducts formed in rat liver compared to the levels seen after treatments with 1,2-dibromoethane. The bis-guanyl adduct represents a cross-linked structure that may be important in the toxicity of this compound. The conjugate was not found to be mutagenic to Salmonella typhimurium TA100 but rather showed a toxic effect toward the bacteria. PMID- 1912334 TI - Hydroxyethylation of hemoglobin by 1-(2-chloroethyl)-1-nitrosoureas. AB - Following treatment of cancer patients with three 1-(2-chloroethyl)-1 nitrosoureas, hemoglobin was isolated and analyzed by GC-MS for N-(2 hydroxyethyl)-N-terminal valine. This alkylated amino acid was liberated as a (pentafluorophenyl)thiohydantoin from the hemoglobin by a modified Edman degradation procedure. Following intravenous infusion of fotemustine [diethyl[1 [3-(2-chloroethyl)-3-nitrosoureido]ethylphosphonate] (ca. 90 mg/m2) the levels of (hydroxyethyl)valine in two patients increased steadily, reaching a peak of ca. 300 pmol/g after 6 h. In a further five patients receiving fotemustine (100 mg/m2) alkylation levels 24 h after treatment ranged from 132 to 1524 pmol/g of globin. Treatment with TCNU [1-(2-chloroethyl)-3-[2 [(dimethylamino)sulfonyl]ethyl]-1- nitrosourea] or ACNU [1-[(4-amino-2 methylpyrimidin-5-yl)methyl]-3-(2-chloroethyl)-3- nitrosourea] resulted in similar increases in (hydroxyethyl)valine in hemoglobin, although the amounts (as with fotemustine) showed considerable interindividual variation. It appears that the measurement of (hydroxyethyl)valine in hemoglobin may be a suitable monitor of exposure to hydroxyethylating agents during (chloroethyl)nitrosourea chemotherapy. PMID- 1912335 TI - Urinary excretion and DNA binding of coal tar components in B6C3F1 mice following ingestion. AB - Urinary excretion of polycyclic aromatic hydrocarbon (PAH) metabolites and DNA binding of coal tar components in male mice were investigated following the ingestion of a coal tar adulterated diet. Male B6C3F1 mice were able to tolerate an F0927 basal gel diet which contained from 0.1 to 1% coal tar (tar weight/dry food weight) for 15 days. Mice maintained on a 0.1 and 0.2% coal tar diet had body weight gains similar to those of control animals. However, mice maintained on the 0.5 and 1.0% diet had body weight gains considerably lower than control values. Chemical-DNA adduct formation was detected and quantified in lung and forestomach tissue of animals on 0.1, 0.2, 0.5, and 1% coal tar containing diets. A dose-related effect was observed in lung DNA adduct formation while no dose effect was observed in forestomach tissue. In addition, overall adduct levels in lung tissue were considerably higher than forestomach levels for animals on the 0.5 or 1% diet. In contrast, DNA adduct levels were highest in the forestomach of animals on diets lower in coal tar content (0.1 or 0.2%). Chemical-DNA adducts of coal tar components were also evaluated for four other coal tar samples which varied in chemical composition. Mice were maintained on diets containing 0.25% of each coal tar for 15 days. Chemical-DNA adducts were detected in lung, liver, and spleen for all animals receiving these coal tar diets. DNA adduct patterns were similar while quantitative differences were observed between coal tar samples and tissue sites. Highest adduct levels were detected in lung DNA. Benzo[a]pyrene content in coal tar samples could not account for the DNA adduct levels observed with coal tar ingestion. The urinary excretion of select PAH metabolites following coal tar ingestion was evaluated by using urine collected on days 1 and 14 of diet administration. The levels of 1-hydroxypyrene in urine, the major PAH metabolite detected, correlated with the pyrene content of these coal tars. These data demonstrate that coal tar components are readily bioavailable following ingestion. PMID- 1912336 TI - Reactive intermediates formed during the peroxidative oxidation of anisidine isomers. AB - The ortho isomer of anisidine (2-methoxyaniline) causes urinary bladder tumors in both mice and rats while the para isomer (4-methoxyaniline) is inactive. Since the urinary bladder contains substantial peroxidase activity, we investigated the peroxidative metabolism of both o- and p-anisidine using horseradish peroxidase as a model enzyme. Both isomers were excellent reducing cofactors for the oxidized state of horseradish peroxidase (HRP), resulting in one-electron oxidation to free radicals. Using high-pressure liquid chromatography, we observed that HRP oxidized p-anisidine to a diimine metabolite which subsequently hydrolyzed to form a quinone imine. Also observed was a dimeric metabolite with an azo bond. Both the diimine and quinone imine metabolites were reactive toward nucleophiles. The quinone imine formed a conjugate with glutathione and was also reduced by glutathione or ascorbic acid. Higher concentrations of substrate (greater than 1 mM) led to the formation of polymeric products (tetramer). Similar metabolites (diimine, quinone imine, azo dimer, polymers) were observed with o-anisidine. Using tritium-labeled anisidine, we observed substantial metabolism-dependent covalent binding of both isomers to protein and DNA. These results demonstrate that horseradish peroxidase dependent metabolism of anisidine isomers yields similar metabolites, although some differences in reactivity of the respective intermediates with nucleophiles were observed. PMID- 1912337 TI - Rat hepatic microsomal metabolism of ethylenethiourea. Contributions of the flavin-containing monooxygenase and cytochrome P-450 isozymes. AB - The contributions of the rat hepatic flavin-containing monooxygenase (FMO) and cytochrome P-450 isozymes (P-450) in the ethylenethiourea (ETU) mediated inactivation of P-450 isozymes and covalent binding of the compound to microsomal proteins were investigated. In vitro, ETU was found to inhibit P-450 marker activities in microsomes obtained from untreated (UT) and phenobarbital (PB), beta-naphthoflavone (BNF), and dexamethasone (DEX) pretreated rats. This inhibition was dependent on the presence of NADPH and was completely abolished by coincubation with glutathione (GSH). Heat treatment of microsomes prior to ETU mediated P-450 inactivation led to diminished loss of P-450 marker activities in microsomes obtained from UT and PB-pretreated, but not BNF- or DEX-pretreated rats, suggesting FMO involvement in the inactivation of some P-450 isozymes. Covalent binding of [14C]ETU to microsomal proteins was found to be NADPH dependent and enhanced with BNF or DEX pretreatment of rats. This binding was completely inhibited by coincubation with GSH. Heat treatment of microsomes and P 450 inactivation studies indicated a predominant role of FMO in the observed covalent binding. Addition of the sulfhydryl reagents dithiothreitol (DTT) or GSH after the incubation of microsomes, [14C]ETU, and NADPH resulted in the complete release of bound ETU, suggesting the reduction of disulfide bonds between oxidized ETU and protein sulfhydryls. Microsomal heme content was not decreased following incubation of microsomes with ETU and NADPH, and P-450 appeared to be converted to P-420.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1912338 TI - On the chemistry of the reaction between N-acetylcysteine and 4-[(4 ethoxyphenyl)imino]-2,5-cyclohexadien-1-one, a 4-ethoxyaniline metabolite formed during peroxidase reactions. AB - 4-Ethoxyaniline (p-phenetidine) is oxidized by peroxidases to form several products, one of which is 4-[(4-ethoxyphenyl)imino]-2,5-cyclohexadien-1-one (1). This compound reacts with N-acetylcysteine (NAC) in methanol-phosphate buffers, generating at least four different products. Four major products, 4-[(4 ethoxyphenyl)amino]phenol (2), 3-(N-acetylcystein-S-yl)-4-[(4 ethoxyphenyl)amino]phenol (3), 2,5-bis(N-acetylcystein-S-yl)-4-[(4-ethoxyphenyl) amino]phenol (4), and 2,5-bis(N-acetylcystein-S-yl)-4-[(4-ethoxyphenyl)imino]-2,5 cyclohexadien-1-one (5), were isolated and identified by NMR spectroscopy and mass spectrometry. The relative ratio between the formed products depends on the pH, the concentration of NAC, and the reaction time. Compound 2, which is the reduced form of 1, was the dominating product when the reaction took place at pH 3, whereas formation of the mono conjugate (3) was more extensive at a neutral pH. Under alkaline conditions 2 and 3 were oxidized by 1 or O2. The oxidized form of 3 was subsequently attacked by a second molecule of NAC, generating the bis conjugate (4). Unless an excess of NAC was present, compound 4 underwent rapid oxidation to 5. Quinone imines, like 1, generating mono conjugates, which are more reactive than the quinone imines per se, are likely to inflict an increased toxic potential and an increased stress on the endogenous thiol pool, resulting in an overall greater toxicity. PMID- 1912339 TI - Structure-activity relationships for intracellular cadmium mobilization by N alkyl-4-O-(beta-D-galactopyranosyl)-D-glucamine-N-carbodithioates+ ++. AB - An examination of a group of dithiocarbamate chelating agents derived from various alkylamines and lactose reveals that the relative potencies in the mobilization of intracellular cadmium from renal and hepatic deposits in mice are highly dependent upon the size and nature of the alkyl groups. For those compounds containing straight-chain alkyl groups, the potency drops off as the number of carbon atoms is increased beyond seven. Branched-chain alkyl groups are more effective in promoting the removal of cadmium than straight-chain alkyl groups with the same number of carbon atoms. The fact that these compounds are effective in the mobilization of intracellular cadmium deposits suggests that the size and shape of the alkyl group are important in the determination of the facility with which the compound can pass through cellular membranes. Straight chain derivatives with 10 or more carbon atoms were more toxic than those with nine or fewer carbon atoms. Of the new compounds, four (the n-hexyl, n-heptyl, n octyl, and 2-ethylhexyl derivatives) are more effective than the corresponding benzyl derivative in inducing a reduction of hepatic cadmium levels from animals given cadmium at least 1 week previously. The results obtained indicate that modest modifications in the groups on the basic dithiocarbamate structure can produce agents of significantly enhanced effectiveness for the removal of cadmium from its hepatic deposits. PMID- 1912340 TI - Internal dynamics of linear and superhelical DNA as studied by photon correlation spectroscopy. AB - Photon correlation spectroscopy has been used to study the translational (D0) and internal dynamics of monodisperse linear and polydisperse superhelical plasmid DNAs. Scattering vector dependent correlation functions were measured and analyzed with the inverse Laplace transform CONTIN written by S. Provencher. For scattering vectors (q) lower than 1.3 X 10(5) cm-1, D0 can be separated from internal dynamics. Using the measured D0 value, the q dependence of internal modes was determined. Extrapolation of the internal relaxation times for q----0 yields the longest internal relaxation time t1. This time can be connected to the persistence length in terms of the Berg-Soda model, which describes the molecule as a semiflexible circular polymer with hydrodynamic interactions. The calculated length of 76 nm for DNA, I = 0.15 mol/L, is a little higher than the one obtained from static light scattering data without excluded volume corrections. A comparison of experimental and simulated correlation functions for the Berg-Soda model shows that the model gives a fairly good description of the dynamics of the linear molecule, whereas large discrepancies between model and experimental functions are observed for the superhelical DNA. Small differences between model and experimental functions are mainly attributed to the neglect of the torsional modes that may be coupled to bending and flexing modes. For the superhelical DNA the agreement is improved if the calculation is carried out with a linear molecule, with shorter contour length and increased diameter. Both quantities can be derived from the known superhelix tilt angle. PMID- 1912341 TI - Antigen-antibody recognition by Fourier transform IR spectroscopy/attenuated total reflection studies: biotin-avidin complex as an example. AB - Biotin-avidin recognition is studied by Fourier transform ir spectroscopy/attenuated total reflection (FTIR/ATR) under physiological conditions. The ureido portion of biotin is confirmed to be involved in the interaction with avidin, as previously found, but when the biotin-avidin complex forms, an electrostatic interaction occurs between the carboxylate group of the biotin molecule and the protonated aminic end group of the avidin amino acid side chains. Comparison of the biotin-avidin system with the biotin-1,4-diaminobutane and biotin-tryptophan systems confirms these findings. PMID- 1912342 TI - Conformational analysis of two cyclic disulfide peptides. AB - Complete nmr and CD studies of two cyclic tetrapeptides with disulfide bonds, Ac L-Pen-L-Pro-D-Val-L-Cys-NH2 (1) and Ac-L-Cys-L-Pro-D-Val-L-Cys-NH2 (2) bonds have been carried out in different solvents to investigate the formation and stabilization of beta-turn structures and to determine the stereochemistry of the disulfide linkage. Both peptides have three-dimensional structures with a type II beta-turn, as derived from quantitative nuclear Overhauser effect data. The combined use of CD and nmr indicates that the dihedral angle of the disulfide bridge is different in the two peptides, although the chirality is maintained. PMID- 1912343 TI - Prediction of fluorine chemical shifts in proteins. AB - Molecular dynamics calculations have been used in an effort to estimate the change in fluorine nmr shielding when a fluorine nucleus enters the tertiary structure of a protein. Considerations of the possible interactions that can define the shift parameter change suggest that van der Waals interactions are the leading determinant of fluorine shifts in proteins, although aromatic ring currents, other magnetic anisotropies, and electrostatic field effects could result in shift distinctions of 1 ppm or smaller. Results of our studies of a fluorine-containing analogue of the ribonuclease A S-protein/S-peptide complex indicate that static structures such as those implied by crystallographic data lead to overestimates of the magnitude of the van der Waals shielding term; molecular dynamics simulations provide indications of the effects of conformational averaging in defining this term. The treatment used predicts the correct direction of the shift change when the fluorine enters this protein environment from aqueous solution and, with an experimentally supported choice of adjustable parameters, gives agreement with the magnitude of the shift. PMID- 1912344 TI - Solution structure of human growth hormone-releasing factor fragment (1-29) by CD: characteristic conformational change on phospholipid membrane. AB - The conformations of synthetic human growth hormone-releasing factor fragment (1 29) in the presence and the absence of 1,2-dimyristoyl-sn-glycero-3 phosphorylglycerol liposome as well as in aqueous 2,2,2-trifluoroethanol solution were investigated by CD spectroscopy. The secondary structure of the peptide in each solution was analyzed by two methods. Both results show that the peptide has an unordered structure in the aqueous solution, whereas it folds into helical structure in the aqueous alcohol and in the phospholipid solution. In addition, although the peptide exists as almost complete helix in the 50 vol% aqueous alcohol (80-90% helicity), it does not reach full helicity even in the solution containing excess amount of phospholipid liposome (maximum 65-70% helicity). The conformational difference is explained by the characteristic amphipathy of the peptide, i.e., the necessity to twist the separated amphipathic helical parts in the interaction with the phospholipid membrane probably makes the helicity of the peptide decrease. PMID- 1912345 TI - Investigation of zinc-binding affinities of Moloney murine leukemia virus nucleocapsid protein and its related zinc finger and modified peptides. AB - Nucleocapsid proteins of retroviruses are small basic, nucleic acid-binding proteins with either one or two "Cys-His" boxes, which have been shown to be involved in genomic RNA dimerization, encapsidation, and replication primer tRNA annealing to the initiation site for reverse transcription. The nucleocapsid (NC) protein of Moloney murine leukemia virus (MoMuLV NCp10) is made up of 56 residues with one Cys-His motif. The Zn(2+)-binding affinities and induced conformational changes of NCp10 were investigated by following the fluorescence of Trp 35 located in the Cys-His domain. At pH 7.5, NCp10 was shown to bind Zn2+ at a 1 : 1 ratio with a very high apparent binding constant of 1.2 (+/- 0.3).10(13)M-1. A similar apparent binding constant was obtained for a 19-residue peptide encompassing the Cys-His box, designated the "zinc finger motif," indicating that it contains most if not all the information to bind Zn2+ tightly. Changing Trp 35 to Phe in the peptide did not affect the Zn2+ affinity, indicating that Trp 35 is not crucial for Zn2+ binding. On the contrary, replacing Cys 29 by Ser, the chemical modification or oxidation of the three Cys sharply reduced Zn2+ affinity, confirming the essential role of Cys in Zn2+ binding. In addition, fluorescence and energy transfer data suggested that Zn2+ binding modifies the Trp 35 environment but not its solvent exposure, and increases the average distance between Tyr 28 and Trp 35 by about 2 A. These data suggest that Zn2+ binding to retroviral NC protein is biologically relevant. PMID- 1912347 TI - Epidemiology of infertility. AB - Recent infertility literature has focused on the epidemiologic evaluation of diagnostic and therapeutic measures. The predictive value of the postcoital test and the sperm penetration assays has been called into question, particularly for female factor infertility. Several studies have sought better prognostic guidelines for assisted reproductive technologies such as artificial insemination by donor and in vitro fertilization and embryo transfer, as well as more cost effective screening measures for evaluating infertile couples. Recent epidemiologic investigations have found no adverse effects of infertility therapy on the health of mothers or their babies. PMID- 1912346 TI - Partial intercalation with DNA of peptides containing two aromatic amino acids. AB - The interactions with DNA of tetrapeptide amides containing lysine at the N terminal position and aromatic amino acids at the second and fourth positions (Ala at position three), 1-6, have been investigated by nmr, CD, and viscometric methods. Tetrapeptides with N-terminal lysine and a single aromatic amino acid, 7 10, were investigated as controls. Significant decreases in DNA viscosity occurred on addition of 7, with the aromatic group at the second position, but not with any of the other single aromatic amino acid peptides. All of the tetrapeptides with two aromatic groups caused DNA viscosity decreases which were two to three times larger than with 7. Peptides with p-nitrophenylalanine (p NO2Phe) as the aromatic group were synthesized for nmr studies because of its simpler aromatic nmr spectrum relative to Phe. Large upfield shifts of the aromatic proton signals were obtained when the amino acid in the second position was L-p-NO2Phe, and the fourth position contained either p-NO2Phe or Phe. Such peptides also caused the largest DNA viscosity decreases on complex formation. Smaller upfield shifts of the aromatic signals were obtained when the amino acid in the second position was L-Phe or a D isomer of Phe or p-NO2Phe. With all peptides, larger upfield nmr shifts were obtained with heat-denatured, recooled DNA than with native DNA under the same conditions. As with nmr, CD results are quite different for the peptides with L and D amino acids at the second position. All of the results can be interpreted in terms of a model in which lysine interacts stereospecifically with the backbone in a DNA double helix and the aromatic group at the second position stacks strongly with the base pairs when the amino acid is an L isomer. The aromatic group at the fourth position can also interact with the base pairs, but primarily through a sideways stacking of the aromatic group with base pairs for either L or D isomers. Because of covalent constraints on the separation distance for the two aromatic groups in the tetrapeptides, they must stack on opposite sides of the same base pair in violation of the neighbor exclusion principle observed with classical intercalators. This stacking at the same base pair no doubt accounts for the larger viscosity decreases in DNA with the peptides containing two aromatic groups relative to those with a single aromatic group.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1912348 TI - Ovulatory dysfunction. AB - Ovulation is the result of a perfectly balanced and coordinated function of endocrine, paracrine, and autocrine systems. Any disruption in the delicately coordinated interaction between the integrated components of the hypothalamic pituitary-ovarian axis may lead to ovulatory dysfunction, a multifactorial entity. The widening scope of knowledge regarding physiology of the reproductive processes as well as rapid development of new diagnostic methods and therapeutic procedures necessitates the continued reassessment and identification of factors leading to ovulatory dysfunction and the design of safe therapy for this condition. The combined use of serial ultrasonography and estradiol measurements should be the standard method of ovulation induction monitoring. The identification of high-risk groups prior to the initiation of ovulation induction regimens must also be taken into consideration if we want to improve pregnancy rate and reduce the incidence of hyperstimulation to a minimal level. PMID- 1912349 TI - Male infertility: the focus shifts to sperm manipulation. AB - Few systemic approaches for treatment of the infertile male are available. Therefore, the focus has shifted to studies of sperm maturation in the female tract, tests of sperm function, and assisted reproduction. New methods of sperm evaluation allow a better determination of those samples that will and will not fertilize ova. These methods include the strict morphology examination, biochemical approaches such as evaluation of creatine kinase levels, and the hemizona assay. Computer assisted semen analysis has not yet proved important for diagnosis but has provided important research information. For example, the drug pentoxifylline significantly increases velocity and has also been shown to enhance in vitro fertilization. The term subfertile is extensively used in the literature but its clear definition and the prognosis for subfertile men have not been established. Approaches that may increase fertilization rates include reducing the gamete culture volume and removal of cumulus oophorus. Assisted reproductive technologies for patients with ejaculatory dysfunction have also been expanded. The use of improved semen processing techniques, advanced oocyte retrieval, and well-timed intrauterine insemination are enabling physicians to use decreasing numbers of viable sperm to achieve pregnancies. PMID- 1912350 TI - Cervico-utero-tubal factors in infertility. AB - Infertility is a common medical problem resulting from one or more defects in the reproductive tract. Of the known causes of infertility, cervico-utero-tubal factors are important because they are generally manageable. Cervical factors include changes in cervical architecture, mucus, or both, resulting in a hostile environment through which sperm must pass. Assessment of this factor includes an evaluation of the cervical mucus both as a transport medium for sperm and as a diagnostic indicator of pending ovulation. Uterine factors include congenital defects and benign tumors resulting in a distorted endometrial surface or a reduced cavitary volume. Surgical reconstruction is of benefit in some cases when other causes of infertility or pregnancy wastage have been effectively managed or ruled out. Tubal factors are among the most common infertility factors and until recently, have only been managed by major invasive surgery. Recently, better assessment of factors leading to tubal obstruction and less invasive tuboplasty or tubal recanalization procedures offer new hope in future management. PMID- 1912351 TI - Repeated pregnancy losses. AB - Our understanding of the causes of repeated pregnancy losses has been expanded during the past year as illustrated from the citations presented from the recent literature in this review. A novel contribution from genetics is the concept of parental gene imprinting, which could help us discuss differences between abnormal embryo and placental development. Advances in immunology, now enable us to use the general term antiphospholipid syndrome to describe pregnancy losses resulting from antibodies to cardiolipin and phosphatidylserine. In addition, other immune causes for pregnancy loss may be present as indicated by the observation that women with circulating antibodies to thyroglobulin or peroxidase are at increased risk for pregnancy loss. Finally, as our knowledge of the cytokines increases, their role in implantation and pregnancy maintenance will be delineated and their dysfunction identified. These disorders will thus become known as the immunodystrophic causes of repeated pregnancy losses. PMID- 1912352 TI - Endometriosis related to infertility. AB - Endometriosis is a disease affecting fertility in many women. However, the mere presence of what is defined as endometriosis cannot be accepted per se as a cause of infertility or an indication for therapy. In the minimal or mild stage the activity rather than the presence should be the criterion for diagnosis as a disease. It is also clear that the endpoint of treatment of endometriosis in infertility is not the elimination of the implants but rather the inactivation or neutralization of its activity. PMID- 1912353 TI - Unexplained infertility. AB - Unexplained infertility is a multifactorial disorder of reproduction. This review examines the potential contribution of decreased uterine perfusion, obscure luteal phase defect, intrinsic endometrial factor ovum captor inhibitor, microscopic endometriosis, and psychologic factors for the cause of unexplained infertility. Although specific therapy for unexplained infertility does not exist and treatment-independent pregnancy frequently occurs in this group of patients, many couples pursue treatment. In vitro fertilization, gamete intrafallopian transfer, zygote intrafallopian transfer, superovulation with intrauterine insemination, and direct intraperitoneal inseminations are several treatment options reported to be successful. However, a randomized prospective study using a uniform diagnostic assessment, strict entry criteria, identical ovulation induction schemes, and semen-processing protocols is lacking to determine which patients will be most appropriately treated with each procedure and which is more effective. Unexplained infertility is not and should not be considered a permanent state. These couples should be considered to be subfertile rather than infertile. PMID- 1912354 TI - Amniocentesis and chorionic villus sampling. AB - Amniocentesis and chorionic villus sampling (CVS) remain the most commonly used invasive prenatal diagnostic procedures. Recent reports on early amniocentesis demonstrate its application to the prenatal detection of certain biochemical disorders. However, its role in the evaluation of open fetal defects of the neural tube or ventral wall is still under investigation. The fact that many reports concerning early amniocentesis include a majority of patients beyond 11 to 12 weeks' gestation, thus placing the procedure outside the first trimester, make comparisons with CVS (usually performed between 9 and 11 weeks) problematic. The role of midtrimester amniocentesis in evaluating elevations of maternal serum alpha-fetoprotein, following a normal ultrasonographic examination performed specifically to detect fetal anomalies, is under scrutiny. It appears that risk adjustment may be appropriate following a normal scan, and prior to invasive procedures, but each center's recommendation to a given patient will depend on the expertise of the individual sonographer, as well as the quality of examination. CVS has gained acceptance as a safe first-trimester means of prenatal diagnosis, with increasing applications in the later stages of pregnancy. Chromosomal mosaicism detected by CVS may represent a phenomenon inherent to placental tissue; questions remain regarding mosaicism as a potential marker for increased pregnancy loss. Comparisons between the transcervical and transabdominal routes are reviewed, with equivalent results regarding safety and efficacy. Recent evaluations of fetomaternal transfusion following CVS are also described. PMID- 1912355 TI - Cystic fibrosis, genetics, and DNA technology. AB - Advances in molecular genetics are leading to changes in practice that have a direct impact on the obstetrician and gynecologist. New techniques of prenatal screening, diagnosis, and potentially therapy are rapidly evolving. Recent developments in cystic fibrosis, preimplantation genetics, fragile X syndrome, neurofibromatosis, muscular dystrophy, and Marfan syndrome are discussed. PMID- 1912356 TI - Fetal health assessment. AB - This review presents a possible rank order in which changes occur in blood flow velocity waveforms, fetal movements, and heart rate patterns in growth-retarded fetuses with progressive deterioration of the fetal condition. With antenatal fetal monitoring, hypoxemia can be diagnosed accurately. The impact of monitoring on (neurologic) morbidity is, however, limited and there is no evidence of a reduction of nervous system dysfunction (cerebral palsy) in newborn infants. Some remarks are made regarding the use of the electronic artificial larynx in fetal testing. PMID- 1912357 TI - Studies of uteroplacental and fetal hemodynamics by Doppler ultrasonography. AB - The role of Doppler ultrasonographic techniques in examining blood velocity waveforms in the different fetal and uteroplacental arteries is evaluated, and the association between pathologic blood velocity waveforms and early signs of disease is reviewed. These areas are discussed with respect to umbilicoplacental circulation, uterine circulation, and fetal cerebral and peripheral hemodynamics. Also reviewed are the use of Doppler techniques to determine the effects of vasoactive agents on the uterine and fetal circulation, and the use of color Doppler imaging in the exact localization of the short and small uterine and fetal vessels. PMID- 1912358 TI - Fetal echocardiography. AB - Fetal echocardiography is an essential technique in the evaluation and management of fetal disease. Recent reviews address the accuracy of the technique, the benefit of routine screening, the association with chromosomal defects, and outcomes in fetuses with the prenatal diagnosis of congenital heart disease. Advances in Doppler have resulted in the more accurate and rapid diagnosis of structural heart disease, and in the use of this technique in the physiological assessment of fetal disease states. PMID- 1912359 TI - Cordocentesis in isoimmunization and fetal physiologic measurement, infection, and karyotyping. AB - Diagnostic cordocentesis is indicated in situations that require fetal vascular access. These include detection of intrauterine TORCH infections, estimation of the extent of fetal anemia before initiating therapy for isoimmunization and determination of fetal hematocrit for appropriate timing of subsequent transfusions. It may also be applied to evaluate fetal acid-base status and rapid karyotyping in fetuses with structural anomalies, intrauterine growth retardation, or oligohydramnios. More recently, it has been used to assist in the diagnosis of intrauterine starvation. Therapeutic applications of cordocentesis include intrauterine transfusion and the administration of medications directly to the fetus. Complications inherent to this procedure include cord hematoma and placental abruption. PMID- 1912360 TI - Fertility and infertility. PMID- 1912361 TI - Prenatal diagnosis. PMID- 1912362 TI - Can we do without mass cervical screening? PMID- 1912363 TI - Fine needle aspiration cytology of the breast: factors affecting sensitivity. AB - At Northampton General Hospital a pathologist takes, stains and immediately reports aspirates at a fine needle aspiration clinic which is run in conjunction with a busy surgical breast clinic. The effect of various factors on the sensitivity of the technique have been quantified. Small tumour size, certain types of tumour and lesions difficult to palpate are causes of reduced sensitivity. Acellular samples had little effect on sensitivity. In this clinic trainee aspirators achieved good results early in their experience. After one year each had improved to the level of an experienced aspirator. PMID- 1912364 TI - C-myc expression in exfoliated cells in serous effusions. AB - In an attempt to improve the discrimination between benign and malignant cells in pleural and peritoneal fluids, 32 effusions were investigated for c-myc expression. Smears were prepared from cells harvested from the fluids for immunocytochemical staining to identify the presence of c-myc protein. Recombinant DNA technology (Northern blotting, slot blotting and in situ hybridization) was used to detect c-myc mRNA. No significant difference in expression of c-myc was noted in benign or malignant effusions. Although the results are inconclusive, the recombinant DNA technology developed for this research could be used to investigate the expression of other oncogenes in cytological material. PMID- 1912365 TI - Effect of ubenimex on the immune system of patients with hematological malignancies. AB - The effect of in vivo administration of ubenimex (Bestatin) on the immune status of patients with hematological malignancies in remission was studied. Natural killer (NK) cell activities, lymphokine activated killer (LAK) cell activities, production of interferon-gamma (gamma-IFN) and surface antigens of peripheral lymphocytes were examined before and after administration of ubenimex. Analysis of the T, B and NK cell compartment ax conducted by assessing expression of the following antigens: CD3+CD19- (T), CD3-CD19+ (B), CD8+CD11b- (Tc), CD8+CD11b+ (Ts), CD4+Leu8-(Th), CD4+Leu8+(Ti), CD16CD57 (NK) using a 2-color flow cytometric analysis. NK and LAK activity was significantly lower in patients with hematological malignancies as compared to normal subjects. The absolute numbers of lymphocytes and NK cells were also lower than those in healthy controls. The reduced NK and LAK activity, however, was elevated after ubenimex administration. The absolute numbers of helper T cells, cytotoxic T cells and NK cells were also increased after administration of the drug. These findings were not observed in patients treated without ubenimex. Serum levels of IFN-gamma were not markedly changed after ubenimex administration. But peripheral blood mononuclear cells cultured with rIL2 showed appreciable levels of IFN-gamma production, and production increased after ubenimex administration. These results shows that ubenimex is a powerful immunomodulator that augments or restores some immune functions in patients with hematological malignancies. PMID- 1912366 TI - Effects of biological response modifiers on childhood ALL being in remission after chemotherapy. AB - Of 125 children with acute lymphoblastic leukemia (ALL), who had been in continuous remission for three years on chemotherapy, 108 patients received biological response modifiers (BRM) such as Bestatin, N-CWS, OK-432 and/or PSK in order to prevent relapse after treatment suspension. From 20 patients who were treated with PSK, 6 relapsed within 13 months. This relapse rate was quite similar to the rate observed with those children who were off therapy (4 relapses in 17 patients within 13 months). In contrast to these 37 patients, only 3 out of 31 patients who received Bestatin (p less than 0.05) and 8 out of 57 patients who received N-CWS or OK-432 relapsed. Based on these findings, BRMs used in the present study seems to be effective to prevent relapse of leukemia among childhood ALL who have electively stopped chemotherapy. PMID- 1912367 TI - Bestatin administration and the change in cellular immunity. AB - The change in cellular immunity by Bestatin (ubenimex) treatment--30 mg/day orally--was investigated in 23 gastrointestinal cancer patients for: 1), functional T cell subsets; 2), IL-2 receptor; 3), PHA-induced blastogenesis; and 4), PPD skin reaction. The absolute number of helper T cells (Th) and cytotoxic T cells (Tc) increased in 74 and 79% of cases, respectively, compared with pretreatment values. On the other hand, the absolute number of suppressor T cells (Ts) decreased in 79% of cases. IL-2 receptor increased in 56% of patients, PHA blastogenesis increased in 67% of patients and PPD skin reaction was elevated in 75% of cases comparing to pretreatment values. These results suggest that Bestatin could increase cellular immunity in cancer patients. PMID- 1912368 TI - Prospective randomized controlled study on bestatin in resectable gastric cancer. AB - The efficacy of Bestatin as adjuvant immunochemotherapy in patients with resectable gastric cancer was investigated. Ninety-six patients with similar background factors were randomized into 2 groups: a control group and an experimental group, the patients in the latter group receiving a daily oral dose of 60 mg Bestatin over a long period. All 96 patients were treated with a bolus intravenous injection of mitomycin C (MMC) plus oral administration of tegafur (FT-207, FT). The survival rate of the patients in the MMC+FT+Bestatin group was more favorable than that of the patients in the MMC+FT group, but the difference was not statistically significant. The survival rates of the MMC+FT+Bestatin group patients in the stratification of stage III+IV and positive histological serosal invasion, ps(+), were significantly superior to those of the MMC+FT group patients (Logrank test: p less than 0.05). Moreover, in patients with positive histological serosal invasion, the recurrence of peritoneal dissemination was significantly suppressed in the MMC+FT+Bestatin group. PMID- 1912369 TI - Bestatin, an aminopeptidase inhibitor with a multi-pharmacological function. AB - Bestatin, the dipeptide N-((2S, 3R)-3-amino-2-hydroxy-4-phenyl butanyl) L-leucine is a leucine aminopeptidase and aminopeptidase-B inhibitor. It exerts a direct stimulating effect on lymphocytes (and monocytes) via its fixation on cell surface leucine-aminopeptidase, and an indirect effect on monocytes (and lymphocytes) via aminopeptidase B inhibition of tuftsin catabolism. Thus it is an immuno-modifier as shown by the Japanese and also our groups: a) immuno-modifier, especially stimulator, in normal young mice; b) immunorestorator and spontaneous tumor preventive agent in aged mice; c) immunorestorator in the elderly and in cancer patients and HIV infected subjects. It stimulates granulocytopoiesis and thrombocytopoiesis in vitro, and can restore them in vivo in myelo-hypoplastic man. The anti-aminopeptidase action of Bestatin also protects enkephalins against their catabolism, which encouraged us, with good preliminary results, to study its analgesic action and search for a preventive effect on "desaddicted" toxicomaniac relapses. PMID- 1912370 TI - Review of ubenimex (Bestatin): clinical research. AB - An immunomodulating agent, ubenimex (Bestatin) has low toxicity even after long term oral administration and brings about significant modifications in immunological response. In a cooperative randomized controlled study of Bestatin immunotherapy for adult acute nonlymphocytic leukemia, prolongation of remission duration and survival was achieved with Bestatin immunotherapy combined with remission maintenance chemotherapy. The significant prolongation of remission duration and survival was seen in the Bestatin group, especially in the elderly patients. Randomized controlled studies of Bestatin immunotherapy were performed in solid tumors including malignant melanoma, carcinoma of the lung, stomach, bladder, head and neck and esophagus, and therapeutic benefits regarding disease free-interval or survival were observed in certain types of the above-mentioned cancers; however, Bestatin immunotherapy for these cancers should be further investigated in large-scale controlled studies to confirm its activity. PMID- 1912371 TI - Hematopoietic and therapeutic properties of bestatin in normal and myelosuppressed mice. AB - Bestatin is a potent inhibitor of aminopeptidase B, an enzyme which is found in abundance in the membrane of monocytes and macrophages. Binding of Bestatin to cells in the histiocytic linage upregulates colony stimulating activity (both in vitro and in vivo), which subsequently increases hematopoietic and hematologic values. We report that the treatment of mice with Bestatin upregulates the frequency and absolute numbers of colony forming unit--granulocyte-macrophage (CFU-GM), as well as the entry of CFU-GM into S phase (a measure of progenitor cell activity). As a result, there is an increase in bone marrow cellularity in cyclophosphamide myelosuppressed mice and an increase in the absolute neutrophil count in normal and myelosuppressed mice. The therapeutic application of this hematopoietic modulator has been demonstrated in combination cyclophosphamide and Bestatin protocols. While Bestatin has significant therapeutic activity for minimal metastatic disease, therapy models in which the hosts have greater metastatic tumor burdens requires combination chemoimmunotherapy for a significant therapeutic effect. Because myelosuppression as a therapeutic indication for Bestatin has only recently been recognized, few clinical studies have been undertaken with appropriate surrogates of hematopoietic activity. However, the preliminary clinical evidence of hematopoietic activity by this non toxic dipeptide, as reviewed here, suggests that this may be an appropriate drug for the treatment of myelosuppressed patients. Thus, Bestatin as an orally active biological response modifier (BRM) has significant therapeutic activity for metastatic disease via multiple mechanisms including hematopoietic stimulation and macrophage activating properties. PMID- 1912372 TI - Enhancing effect of ubenimex (bestatin) on proliferation and differentiation of hematopoietic progenitor cells, and the suppressive effect on proliferation of leukemic cell lines via peptidase regulation. AB - Ubenimex (Bestatin) significantly enhanced the G- and GM-CSF-induced colony formation of human bone marrow cells at concentrations of 0.001, 0.01, 0.1 and 1.0 microgram/ml (21-61% enhancement), but not at 10 micrograms/ml. Ubenimex did not influence the EPO-induced erythroid colony and burst formation between 0.0001 100 micrograms/ml. Against human and mouse leukemic cell lines, the growth inhibitory activities of ubenimex were dose-dependently observed. Aminopeptidase activities on U937 and TF-1 cells were almost inhibited with 10 and 100 micrograms/ml of ubenimex, respectively. Cross-linking studies of 125I-GM-CSF binding to TF-1 cells demonstrated that the 150-kDa band of 2 major bands was enhanced after incubation with 0.01 microgram/ml ubenimex but decreased after that with 100 micrograms/ml, and that the 95-kDa band was not changed at any concentration of ubenimex. Change in density of the 150-kDa band on ubenimex treated TF-1 cells was correlated with that in expression of CD10 (neutral endopeptidase) on them, whereas that in expression of CD13 (aminopeptidase N) was not changed at any concentration. These results suggest that one possible mechanism of ubenimex action in hematopoietic progenitor cells is the up regulation of the high affinity receptor for GM-CSF and that in leukemic cell lines is suppression of amino acid incorporation via peptidase regulation. PMID- 1912373 TI - Bestatin treatment of myelodysplastic syndromes and chronic myelogenous leukemia. AB - A high remission rate (56%) was achieved in a preliminary study using Bestatin in patients with myelodysplastic syndromes. In particular, 9 out of 13 patients (69%) in the high blast group achieved hematologic remission. After Bestatin treatment, intrinsic hematopoietic stem cell abnormalities as well as hematologic findings were markedly improved. The success of Bestatin therapy in MDS led us to investigate the clinical activity of Bestatin in CML. In the current study the busulfan and Bestatin combination therapy resulted in complete hematologic remission in all of the patients. The most exciting result was the suppression of the Philadelphia chromosomes among the responding patients. Complete cytogenetic response was obtained in 3 patients (21%), partial cytogenetic response in 1 (7%), and minor cytogenetic response in 5 (36%). In particular, the majority of early chronic phase CML patients achieved significant cytogenetic response with sustained Ph1 negativity. The results are very encouraging and warrant further studies. PMID- 1912374 TI - Effects of ubenimex, a biological response modifier, on myelodysplastic syndrome and chronic leukemia. AB - Twenty cases of myelodysplastic syndrome (MDS) were treated with ubenimex. Seventeen cases were treated with the drug over 90 d. Among these, 10 showed improvement of anemia, 12 an increase in platelet count which had decreased before treatment and 10 an increase in neutrophil count; however, 14 showed an increase in blast percentage in bone marrow aspirate. CD4/CD8 ratio was increased in 4 cases and shifted to a normal from an abnormal range in 6 cases. When the MDS cases were observed in refractory anemia (RA) and refractory anemia with excess blasts (RAEB), great improvement was seen, but in RAEB increase in blast percentage was also observed. CD4 increased mostly in RA and CD8 increased in RAEB. Ten cases of chronic myelocytic leukemia (CML) were first treated with ubenimex and cytostatics, then with ubenimex only. Six cases attained partial remission within 3 months, but one case showed a marked increase in white cell count and blast count and in another case a progression of splenomegaly associated with increase in white cell count. From these findings we conclude that ubenimex could be utilized in MDS or CML if the patient was at risk for strong chemotherapy. PMID- 1912375 TI - The lesson of the Chernobyl disaster. AB - On April 26, 1986 a major nuclear disaster took place at 1 h 24 min local time, destroying the fourth reactor of the Chernobyl plant. Five years later the consequences of the disaster are still not fully known. Nevertheless the long term future of nuclear energy in the world is uncertain. Questions need to be answered by observing hard facts if emotional attitudes are not to prevail over reality. The reactor and its core were destroyed by an explosion, causing two radioactive jet emissions of iodine 131, followed by caesium 137. Both elements are mainly incorporated in the body via food. The Chernobyl disaster was a consequence of inadequate safety regulations and human error. Enforcement of strict regulations are likely to be highly effective in preventing a further catastrophe. However, governments should consider another possibility. What would be the consequences for public health if a terroristic act deliberately destroyed a nuclear power station? PMID- 1912376 TI - Introduction: present knowledge on the effects of radioactive contamination on pregnancy outcome. AB - This introduction gives a brief review of the effects on pregnancy outcome that might follow radioactive contamination of the environment. These include miscarriages, congenital anomalies, damage to the central nervous system expressed through reduced intelligence and a risk of tumours late in life. Knowledge is fragmentary and field studies are difficult, which lends weight to the attempts at studying the effects of the Chernobyl accident in Europe which are the subject of the present symposium. PMID- 1912377 TI - Incidence of legal abortion in Sweden after the Chernobyl accident. AB - The number of legal abortions in Sweden increased around the time of the Chernobyl accident, particularly in the summer and autumn of 1986. Although there was no recording of reasons for legal abortions, one might have suspected this increase to be a result of fear and anxiety after the accident. However, seen over a longer time perspective, the increase in the number of abortions started before and continued far beyond the time of the accident. There was also a simultaneous and pronounced increase in the number of births during the years subsequent to the accident. Therefore, it seems unlikely that fear of the consequences of radioactive fall-out after the Chernobyl accident resulted in any substantial increase of the number of legal abortions in Sweden. PMID- 1912378 TI - Legally induced abortions in Denmark after Chernobyl. AB - During the months following the accident in Chernobyl, Denmark experienced an increasing rate of induced abortion, especially in regions with the largest measured increase in radiation. As the increase in radiation in Denmark was so low that almost no increased risk of birth defects was expected, the public debate and anxiety among the pregnant women and their husbands "caused" more fetal deaths in Denmark than the accident. This underlines the importance of public debate, the role of the mass media and of the way in which National Health authorities participate in this debate. PMID- 1912380 TI - The effects of the Chernobyl explosion on induced abortion in Italy. AB - Four regression models have been fitted to data of the monthly number of induced abortions in Italy between January 1984 and April 1986, in order to predict the number which would have occurred in the 5 months following the Chernobyl explosion. In model I the average number of abortions per day in each month was the dependent variable and calendar months, a linear time trend and previous month's value were the independent variables. Model II included a quadratic time trend term in addition to the independent variables used in model I. Models III and IV were like models I and II except that the dependent variable was the average number of abortions per working day in each month and the effect of the previous month's value was omitted. The 4 models all implied that an excess number of abortions were performed in the 5 months following the Chernobyl accident. The mean daily excess was estimated to be 28 and 52 per day for models I and II and the mean excess per working day was estimated to be 20 and 30 by models III and IV, respectively. Clearly the estimated magnitude of the excess depends on whether the quadratic time trend is included among the explanatory variables, but these results imply that the excess is unlikely to be merely due to chance. PMID- 1912379 TI - Pregnancy outcome in Norway after Chernobyl. AB - Pregnancy outcome has been studied in terms of legal abortions, early spontaneous abortions and total number of pregnancies (in an ad hoc study covering 6 counties) as well as various perinatal health problems (on the basis of routinely recorded data for epidemiological surveillance from the Medical Birth Registry of Norway). Apparently, no effects were observed in terms of an increased occurrence of legal abortions, while spontaneous abortions increased from 7.2% of all pregnancies during the last 12 months before the accident to 8.3% after the accident [corrected]. At the same time, the total number of pregnancies somewhat decreased. Based on monthly measurements in each municipality of external and internal (food-based) doses, dose-response associations were assessed for a number of perinatal health problems. No associations were observed. PMID- 1912381 TI - Incidence of legal abortions and congenital abnormalities in Hungary. AB - The annual and monthly distributions of congenital abnormalities and pregnancy outcomes as confounding factors were evaluated in Hungary in reflection of the accident at the Chernobyl reactor. The different congenital abnormality entities and the components of fetal radiation syndrome did not show a higher rate after the Chernobyl accident in the data-set of the Hungarian Congenital Abnormality Registry. Among confounding factors, the rate of induced abortions did not increase after the Chernobyl accident in Hungary. In the 9th month after the peak of public concern (May and June, 1986) the rate of livebirths decreased. Three indicator conditions: 15 sentinel anomalies as indicators of germinal dominant gene mutations, Down syndrome as an indicator of germinal numerical and structural chromosomal mutations, and unidentified multiple congenital abnormalities as indicators of germinal dominant gene and chromosomal mutations were selected from the material of the Hungarian Congenital Abnormality Registry. Diagnoses were checked, familial and sporadic cases were separated and only the sporadic cases were evaluated. The analysis of indicator conditions did not reveal any measurable germinal mutagenic effect of the Chernobyl accident in Hungary. PMID- 1912382 TI - Pregnancy outcome in Finland after the Chernobyl accident. AB - The explosion at the Chernobyl nuclear power plant caused radioactive fallout in Finland in April-May 1986. The fallout was unevenly distributed geographically, and, accordingly, the country was divided into 3 fallout zones. Whole-body radioactivity measurements of randomly chosen persons showed that the regional differences prevailed throughout the following 2 years. Data for legal abortions, registered congenital malformations as well as preterm births and stillbirths of malformed children were collected. The corresponding expected figures were obtained from statistics from 1984 and 1985. No differences in the expected/observed rates of the above parameters were detected. PMID- 1912384 TI - Homochirality and stereospecific activity: evolutionary aspects. AB - The problem discussed in this paper is the connection between the unique property of biopolymers (proteins, DNA and RNA), i.e. homochirality, and their main functional property, i.e. self-replication. Our approach is based on an analysis of the conditions for the origination of the mechanism of self-replication of chiral polymers. It is demonstrated that self-replication could originate only on the basis of homochiral structures, possessing stereospecific (enzymatic) activity. It is also shown that complete breaking of the mirror symmetry of the organic medium is required both at the stage of polymeric takeover and at the stage of formation of structures possessing stereospecific activity. This requirement is satisfied only in the framework of the mechanism of spontaneous symmetry breaking i.e. the mechanism of non-equilibrium phase transition from the racemic state of the organic medium to the chirally pure one. The results obtained suggest that homochirality is a necessary condition for the origination of biological specificity and plays a fundamental role in the formation of structures capable of self-replication. PMID- 1912383 TI - Surfactant micelles containing protoporphyrin IX as models of primitive photocatalytic systems: a spectral study. AB - Micelles of various surfactants containing protoporphyrin IX (PPIX) have been studied as models of primitive membrane-like photocatalytic systems. Spectral characteristics (absorption spectra, fluorescence emission and excitation spectra, fluorescence quantum yields and lifetimes) have been measured to indicate specific interactions of PPIX molecules with the micelles. Two types of PPIX aggregates are probably formed in water: non-fluorescent clusters corresponding to the absorption peak at 642-648 nm and fluorescent friable dimers with strong solute-solvent interactions corresponding to the absorption peak at 618 nm. The aggregates are solubilized by the micelles, which results in an increase of the fluorescence quantum yield (and thus in the increase of the PPIX sensitizing ability). Solubilization of PPIX molecules by SDS-micelles is enhanced by the partial neutralization of the negative surface charge of the micelles. Neutral Triton X-100 micelles solubilize PPIX much better than SDS particles; however, some of the clusters formed in the bulk aqueous phase of the detergent-water system remain aggregated in the crown of the micelle. The positively charged CTAB micelles have been shown to provide the best solubilization of PPIX accompanied by the highest increase of its emitting activity. The results are discussed in terms of the possible role of PPIX containing membraneous systems in primitive photosynthesis. PMID- 1912385 TI - Time reverse automata patterns generated by Spencer-Brown's modulator: invertibility based on autopoiesis. AB - In the present paper the self-consistency or operational closure of autopoiesis is described by introducing time explicitly. It is an extension of Spencer Brown's idea of time, however. The definition of time is segregated into two parts, corresponding to the syntax and semantics of language, respectively. In this context, time reversibility is defined by the formalization of the relationship between time and self-consistency. This idea has also been discussed in the context of designation and/or naming. Here we will discuss it in the context of cellular automata and explain the structure of one-to-many type mappings. Our approach is the first attempt to extend autopoietic systems in terms of dynamics. It illustrates how to introduce an autopoietic time which looks irreversible, but without the concept of entropy. PMID- 1912386 TI - Generalized Stein's model for anatomically complex neurons. AB - A neuron with a large dendritic structure is considered. The number of synapses located on the dendrites is substantially higher than on the soma. The synaptic input effect on the neuronal excitability decreases with distance between a synapse ending and the trigger zone. Two areas are distinguished in accordance with the effect of synaptic input--dendritic and somatic. The dendritic area, when compared to the soma, is characterized by much higher intensity of its activation but the amplitudes of synaptically evoked changes of the membrane potential at the trigger zone are in general small. This situation is suitable for a diffusion approximation. However, on the soma, especially in the proximity of the trigger zone, the membrane potential changes are a large fraction of the threshold depolarization. The membrane potential at the trigger zone is modelled by a one-dimensional stochastic process. The diffusion Ornstein-Uhlenbeck process serves as a basis of the model; however, at the moments of somatic synapses activation its voltage changes in jumps. Their sizes represent the amplitudes of the evoked postsynaptic potentials. The unimodal histograms of interspike intervals can be explained by the model. The values of the coefficient of variation greater than one are connected with substantial inhibition. PMID- 1912387 TI - Elevated levels of stress proteins associated with bacterial symbiosis in Amoeba proteus and soybean root nodule cells. AB - Obligatory bacterial endosymbionts of Amoeba proteus and symbiotic Bradyrhizobium japonicum bacteroids in soybean-root nodules contained large amounts of 67-kDa and 65-kDa proteins, respectively, antigenically related to groEL of E. coli and the 58-kDa heat-shock protein of Tetrahymena. Monoclonal antibodies against the 67-kDa protein recognized groEL analogs from several different organisms. The quantity of the stress protein in symbiotic B. japonicum bacteroids was augmented seven times that in the free-living counterparts. The increase in these proteins in endosymbionts, as determined by immunoblot techniques, indicated that intracellular symbiosis is a stress condition even when the symbiotic relationship is considered to be mutually beneficial. Mitochondria and chloroplasts may also be under a stressed condition like endosymbionts in view of the presence of heat-shock proteins in these cell organelles. PMID- 1912390 TI - Nephrologists' reported attitudes about factors influencing recommendations to initiate or withdraw dialysis. AB - A nationwide survey of nephrologists was performed to learn which patient factors and characteristics of nephrology fellowship training they reported as influencing their decisions to start or stop dialysis. One hundred seventy-four of 482 responses were received. Most respondents were men in private practice living in large communities (41% in communities over 1,000,000 population). Most had completed a 2-yr fellowship (88%) at a medical school hospital (75%). Few (9%) received formal instruction in medical ethics during fellowship training, and only one quarter had informally discussed life-sustaining treatments during training. Neurological status was the most, and age the least, important patient factor reported to influence decisions to start or stop dialysis. No respondent demographic factors correlated with ranking of patient factors in decisions to initiate or forego dialysis. Family wishes and preexisting medical conditions were significantly more important considerations in initiating than in stopping dialysis. Insights about the factors practicing nephrologists reportedly weigh most heavily in making the difficult decisions to withhold or withdraw dialysis are provided by this study. Additional study of the actual practices of nephrologists in decisions to initiate or withdraw dialysis and the factors influencing those decisions are needed. Formal instruction in these and other ethical problems confronting nephrologists should perhaps be included in fellowship programs. PMID- 1912388 TI - New insights into the cell biology of ischemic acute renal failure. AB - Proximal tubule cells play an essential role in the reabsorption of ions, water, and solutes from the glomerular filtrate. This is accomplished, in large part, by having a surface membrane polarized into structurally, biochemically, and physiologically distinct apical and basolateral membrane domains separated by cellular junctional complexes. Establishment and maintenance of these unique membrane domains are essential for the normal functioning of the cell. Ischemia results in the duration-dependent loss of apical and basolateral surface membrane lipid and protein polarity. Loss of surface membrane polarity is preceded by disruption of the microfilament network and opening of cellular tight junctions. Surface membrane lipids and proteins are then free to diffuse laterally within the bilayer into the alternate membrane domain. Functionally, ischemia-induced loss of epithelial polarity has been shown to be responsible for reduced sodium and glucose reabsorption. Reduced Na+ reabsorption has been related to redistribution of Na+, K(+)-ATPase into the apical membrane. During recovery from ischemic injury, proximal tubule cells undergo remodeling of the surface membrane such that the unique apical and basolateral membrane domains are reestablished, allowing for the return of normal cellular function. PMID- 1912389 TI - Nitric oxide: a potential mediator of amino acid-induced renal hyperemia and hyperfiltration. AB - The role of nitric oxide in the modulation of systemic and renal hemodynamics was examined by using N omega-monomethyl-L-arginine (L-NMMA, 110 micrograms/kg/min), a competitive inhibitor of the conversion of L-arginine to nitric oxide. L-NMMA or saline vehicle (9.6 microL/min) was infused intravenously into anesthetized euvolemic Munich-Wistar rats. After 30 min, L-NMMA resulted in a uniform increase in mean arterial blood pressure (111 +/- 1 to 128 +/- 2 mmHg; P less than 0.05) and a modest reduction in renal plasma flow rate (4.4 +/- 0.2 to 4.2 +/- 0.1 mL/min; P less than 0.05), without change in glomerular filtration rate (1.16 +/- 0.03 to 1.15 +/- 0.03 mL/min); vehicle had no effect on these renal parameters. These rats were then subdivided to receive an intravenous infusion (37 microL/min) of either 10% glycine, 11.4% mixed amino acids, or equiosmolar dextrose. L-NMMA pretreatment markedly attenuated glycine-induced hyperfiltration (10 +/- 6 versus 33 +/- 5%, L-NMMA versus vehicle; P less than 0.05) and obliterated the renal hyperemic response (-7 +/- 6 versus 16 +/- 4%, L-NMMA versus vehicle; P less than 0.05). L-NMMA also caused modest blunting of the mixed amino acid-induced hyperfiltration (18 +/- 4 versus 30 +/- 4%, L-NMMA versus vehicle; P = 0.056) but failed to curtail the renal hyperemia (16 +/- 6 versus 20 +/- 4%). Dextrose had no effect on glomerular filtration rate or renal plasma flow.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1912391 TI - Plasma oxalate levels rise in hemodialysis patients despite increased oxalate removal. AB - The cause of secondary hyperoxalemia and oxalosis in patients on maintenance dialysis is unknown. The oxalate removal rate was determined in 26 patients on maintenance hemodialysis and 6 on continuous ambulatory peritoneal dialysis by measuring oxalate removed by dialysis and urinary excretion. The role of vitamin B6 deficiency and ascorbate in the raised plasma oxalate concentrations of these patients was evaluated. Plasma oxalate in hemodialysis patients, 442 +/- 41 micrograms/100 mL (mean +/- SE), and peritoneal patients, 394 +/- 115 micrograms/100 mL, were significantly higher than that in normal subjects, 11 +/- 1 microgram/100 mL (P less than 0.001). Average daily oxalate removal in subjects on hemodialysis, based on dialysis losses and urinary excretion, 35 +/- 3 mg/24 h, was significantly greater than urinary excretion of normal subjects, 26 +/- 1 (P less than 0.01). Oxalate removal from peritoneal dialysis patients, 28 +/- 2 mg/24 h, was not significantly different from that of hemodialysis patients or urinary excretion of normal subjects. Plasma ascorbate and B6 status were not correlated with plasma oxalate. A positive correlation between B6 deficiency and oxalate removal rate was not found. Plasma oxalate was correlated with time on dialysis (all patients) (P = 0.02). In a separate study of 15 hemodialysis patients followed over 2.3 +/- 0.2 yr, both plasma oxalate and oxalate removal rate significantly increased, P less than 0.001 and 0.05, respectively. It was concluded that oxalate removal rate is increased in hemodialysis patients and that the increased total body oxalate burden in these patients is not due to decreased removal. Although the increase may result from increased oxalate synthesis or gastrointestinal absorption, B6 deficiency and increased plasma ascorbate do not play a role. PMID- 1912392 TI - Aluminum uptake and toxicity in cultured mouse hepatocytes. AB - Hepatic aluminum (Al) accumulation in association with hepatobiliary dysfunction has been described in children receiving contaminated parenteral alimentation solutions and in aluminum-overloaded experimental animals. The mechanisms of hepatic Al uptake are not clearly understood, and it is not known whether Al is directly toxic to the hepatic cell or if toxicity occurs from the effect of Al on hepatic iron (Fe) metabolism. Al causes a microcytic hypochromic anemia and concomitant hepatic Al and Fe can accumulate in dialysis patients, suggesting that Al may alter Fe metabolism. Therefore, Al uptake and toxicity were studied in mouse hepatocytes in culture. Al accumulation, cell growth, media hepatic enzyme concentrations, and cell malonyldialdehyde concentrations, a marker of membrane lipid peroxidation, were measured in mouse hepatocytes grown in media containing either Al citrate, transferrin-Al (Tf-Al), or no additions over 96 h. Al uptake occurred only in cells grown in Tf-Al and Al citrate at 24 h and increased linearly achieving cellular concentrations at 96 h of 522 +/- 36 and 186 +/- 12 micrograms/L, respectively, compared with 31 +/- 3 micrograms/L (P less than 0.001) in control media. Inhibition of cell growth occurred at 48, 72, and 96 h (P less than 0.001), and media lactate dehydrogenase and aspartate aminotransferase concentrations increased starting at 48 and 72 h, respectively (P less than 0.001), only in media containing Tf-Al. Cell malonyldialdehyde levels were significantly higher in Tf-Al-loaded mouse hepatocytes compared with control cells at 96 h (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1912393 TI - Elemental microanalysis of organelles in proximal tubules. I. Alterations in transport and metabolism. AB - Oxygen deprivation to the kidney causes a multifactorial series of morphological, physiological, and biochemical alterations that occur as a function of time. One of the earliest events involves significant changes in the cellular contents of the physiologically important elements (ions) Na and K. Controversy exists as to the nature of changes in the content of the regulatory ion Ca, in either its free or bound form, and much less is known regarding in situ distribution and amounts of other elements such as Mg, P, S, and Cl during physiological or pathophysiological states. The objective of these studies was to evaluate element compartmentation in proximal renal tubules by using quantitative electron probe x ray microanalysis, during specific conditions which are at least partially manifested during oxygen deprivation. Cells from control proximal tubule suspensions were compared with those exposed to (1) ouabain, to inhibit (Na+, K+) ATPase; (2) mitochondrial uncouplers, to rapidly deplete ATP content; or (3) calcium ionophores, to cause a rapid elevation in cytoplasmic free calcium. In parallel with electron probe x-ray microanalysis imaging of subcellular elemental content, total cell potassium and ATP contents, enzyme release, oxygen consumption, cytoplasmic free calcium levels, and ultrastructural alterations were assessed. Results indicated that ATP depletion was, in the short term, more deleterious to renal proximal tubules than any of the tested ionic alterations. Intracellular organelles including mitochondria and nuclei appeared to be readily permeable to Na, K, and Cl, altering their concentrations of these ions in parallel with cytoplasmic concentrations. Lysosomes exhibited evidence of Cl accumulation, consistent with an inwardly directed proton ATPase with accompanying Cl transport. Whereas in the cytoplasm Na, K and Cl appeared to be mostly free, a large fraction of these ions within intracellular organelles seemed bound. PMID- 1912394 TI - Elemental microanalysis of organelles in proximal tubules. II. Effects of oxygen deprivation. AB - This communication describes the effects of anoxia on rabbit proximal renal tubule element (ion) content by using high-resolution electron probe x-ray microanalytical imaging to obtain quantitative elemental data from subcellular compartments not previously resolvable with low-resolution imaging. These organelles and regions include the heterochromatin and euchromatin of the nucleus and the microvilli of the apical brush border, in addition to mitochondria, lysosomes, and cytoplasm. Anoxia of 40-min duration caused the expected decrease in K and increase in Na and Cl concentrations in the tubules with the cytoplasmic K:Na ratio declining to 0.13:1. These changes were accompanied by decreases in ATP and total K contents, and an increase in lactate dehydrogenase release. Swelling occurred in some cells as evidenced by ultrastructural changes. No alterations were evident after oxygen deprivation in Ca content of cytoplasm (control, 6.7 +/- 0.6 versus anoxia, 7.6 +/- 0.7 nmol/mg dry wt) or mitochondria (control, 4.0 +/- 0.4 versus anoxia, 4.9 +/- 0.6 nmol/mg dry wt) or in S content of recognizable lysosomes (control, 314 +/- 11 versus anoxia, 325 +/- 12 nmol/mg dry wt). Brush border (microvillus) Ca content was higher than cytoplasmic Ca content during normoxia (10.7 +/- 0.9 nmol/mg dry wt) and increased further during anoxia (17.0 +/- 1.0 nmol of Ca/mg dry wt). The finding of higher Ca content within the brush border region during normoxia is unexpected and novel, because such results suggest that Ca homeostasis in the apical elaboration of the proximal cell may be different from that in the cytoplasm. The results also raise the possibility that an increase in Ca content in the brush border membrane region may be involved in the pathogenesis of renal cell injury. PMID- 1912395 TI - Fibronectin mRNA and protein accumulation, distribution, and breakdown in rabbit anti-glomerular basement membrane disease. AB - Fibronectin is a multifunctional matrix protein which by immunofluorescence appears to be present in increased amounts during glomerular injury. To examine fibronectin metabolism in glomerular injury, an anti-glomerular basement membrane model that progresses to severe glomerular crescent formation, glomerulosclerosis, and interstitial fibrosis was used. Fibronectin was purified from rabbit plasma, and a monoclonal antibody raised against rabbit fibronectin was used for immunolocalization and quantitation of fibronectin protein. RNA and protein were extracted from isolated glomeruli and whole renal cortex at various times during progression of disease. At day 4, there was a 2.5-fold increase in fibronectin protein which by immunofluorescence appeared to be in the glomerular mesangial area. There was no increase in glomerular fibronectin mRNA at this time. This discrepancy is consistent with the conclusion that, at this early time point, the increased glomerular fibronectin comes predominantly from plasma. By day 7, glomerular fibronectin mRNA and extractable fibronectin protein were increased in association with bright immunofluorescence along the inner aspect of Bowman's capsule where early crescents were forming. Similarly, at day 14, crescents stained very brightly for fibronectin. These results are consistent with the conclusion that, at later time points, fibronectin is synthesized in glomeruli in association with cell division and crescent formation. Degradation of fibronectin in glomerular and cortical extracts was demonstrated under normal and nephritic conditions by finding fibronectin proteolytic fragmentation by Western blot.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1912397 TI - Stars and stripes: a patriotic grant proposal. PMID- 1912396 TI - Chronic effects of omega-3 fatty acids (fish oil) in a rat 5/6 renal ablation model. AB - It has been proposed that fish oil dietary supplementation in the chronic rat 5/6 renal ablation model may be either protective or toxic. These conflicting hypotheses were tested in rats who underwent renal ablation or sham surgery. Twenty rats received sham surgery, and 40 received 5/6 renal ablation. All rats were fed a regular laboratory diet up to 1 week postsurgery. At that time, one half of the renal ablation group was provided with an isocaloric diet supplemented with 24% MaxEPA (fish oil), 1% safflower oil, and antioxidants. The renal ablation rats developed hypertension, albuminuria, gammaglobulinuria, and a decline in glomerular filtration rate, which was less in the fish oil group compared with that in the regular laboratory diet group at 10 and 20 wk postsurgery. The fish oil renal ablation rats had significantly less glomerulosclerosis than did the regular laboratory diet renal ablation animals, and no more glomerular fibrin deposition than did the sham controls. The renal ablation regular laboratory diet rats had a significant dyslipidemia at 20 wk which was prevented in the fish oil renal ablation cohort. The fish oil renal ablation rats also demonstrated a significant decline in renal tissue arachidonic acid incorporation and a concomitant increase in eicosapentaenoic acid and docosahexaenoic acid incorporation. The mortality of the renal ablation group was greater than that of the sham controls but not significantly different for the fish oil or the regular laboratory diet groups. These results support the hypothesis that the fish oil diet containing specific antioxidant, vitamin E, and essential fatty acid supplementation is protective in the rat remnant nephron model and prevents the evolution of glomerulosclerosis with associated renal functional impairment, while preserving glomerular filtration. PMID- 1912398 TI - The role of the American Society of Nephrology in shaping health policy. PMID- 1912399 TI - The American Society of Nephrology-1990: an assessment of the present and objectives for the future. PMID- 1912400 TI - Glue-sniffing and distal renal tubular acidosis: sticking to the facts. AB - An index case is presented to introduce the subject of the acid-base and electrolyte abnormalities resulting from toluene abuse. These include metabolic acidosis associated with a normal anion gap and excessive loss of sodium and potassium in the urine. The major question addressed is, what is the basis for the metabolic acidosis? Overproduction of hippuric acid resulting from the metabolism of toluene plays a more important role in the genesis of the metabolic acidosis than was previously believed. This conclusion is supported by the observation that the rate of excretion of ammonium was not low during metabolic acidosis in six of eight patients, suggesting that distal renal tubular acidosis was not an important acid-base abnormality in most cases where ammonium was measured. The excretion of hippurate in the urine unmatched by ammonium also mandates an enhanced rate of excretion of the cations, sodium and potassium. The loss of sodium causes extracellular fluid volume contraction and a fall in the glomerular filtration rate, which may transform the normal anion gap type of metabolic acidosis into one with a high anion gap (accumulation of hippurate and other anions). Continuing loss of potassium in the urine leads to hypokalemia. An understanding of the metabolism of toluene provides the basis for the unusual biochemical abnormalities seen with abuse of this solvent. PMID- 1912401 TI - Culture of renal tubular cells from the urine of patients with nephropathic cystinosis. AB - Nephropathic cystinosis represents a prototype for lysosomal storage diseases and is the most common cause of renal tubular Fanconi's syndrome. Mechanisms of the tubular transport defects in this disease have not been defined, however, in part because the cells readily cultured from affected patients, leukocytes and fibroblasts, do not express epithelial transport functions. Except for a single autopsy report, renal tubular cells from these patients have not been studied in vitro. In these studies, noninvasive harvesting and culture of renal tubular cells from the urine of patients with cystinosis is described. Cultures of renal tubular cells could be established from over 50% of the isolates which contained viable cells and which remained uncontaminated in vitro. Cells had an epithelial morphology in culture, and the majority of cultured cells expressed proximal tubular brush border marker enzyme. Cultured cells also expressed the storage defect in vitro, containing cystine levels up to 100 times those of normal cells. Cultured cells could be depleted of cystine by using the thiol cysteamine. This in vitro model system should be very useful for studying the mechanisms of renal tubular transport defects in this disease. PMID- 1912402 TI - Response of insulin-like growth factor I and renal hemodynamics to a high- and low-protein diet in the rat. AB - An increase in plasma insulin-like growth factor I (IGF-I) levels by growth hormone injection or IGF-I infusion can raise renal plasma flow and glomerular filtration rate. However, it is not known whether a more physiological stimulus for IGF-I will also increase IGF-I in the kidney and whether the increase in renal or serum IGF-I is correlated with the increase in renal plasma flow and glomerular filtration rate. Male rats were pair fed either a high-protein (36% protein, N = 9) or a low-protein but isocaloric diet (9% protein, N = 9) for 10 to 14 days. Renal plasma flow and glomerular filtration rate were then estimated by clearance measurements, and IGF-I was measured in extracted serum, liver, renal cortical tissue, and glomeruli. Body weight gain and combined kidney weight were higher in high-protein rats as compared with low-protein animals (0.86 +/- 0.02 SEM versus 0.77 +/- 0.02 g/100 g body wt; P less than 0.05), but liver weights were not different. Serum, liver, and glomerular IGF-I levels were also higher in the high-protein rats as compared with the low-protein animals (serum, 1.12 +/- 0.03 versus 0.80 +/- 0.06 U/mL, P less than 0.05; liver, 183 +/- 17 versus 117 +/- 16 mU/g wet wt, P less than 0.05; glomeruli, 7.43 +/- 0.73 versus 4.81 +/- 0.59 mU/mg of protein, P less than 0.05). In contrast, the renal cortical IGF-I levels were not different in high-protein versus low-protein rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1912403 TI - Elevated proto-oncogene expression in polycystic kidneys of the C57BL/6J (cpk) mouse. AB - Polycystic kidney disease in the C57BL/6J (cpk) mouse is an autosomal recessive disorder which leads to the rapid development of renal cysts and kidney failure during the first 3 to 4 postnatal weeks. Previously, we showed that the cystic kidneys of affected mice have abnormally elevated levels of c-myc mRNA. In the study presented here, it is shown that mRNAs for the proto-oncogenes c-fos and c Kiras, as well as c-myc, are markedly elevated in cystic kidneys, suggesting that there is a more general abnormality in gene expression associated with the disease. It is also evident that there are two stages to this abnormal proto oncogene expression. In the first stage, which occurs up through the second postnatal week, there are modest increases in proto-oncogene mRNA which parallel the increased cell proliferation that accompanies cyst growth at this time. In the second stage, which occurs after the second postnatal week, there are markedly elevated levels of proto-oncogene mRNA that are seen at a time when cell proliferation is declining. The development of this latter stage suggests either that there is a fundamental abnormality intrinsic to polycystic kidneys that leads to uncontrolled proto-oncogene expression later in disease progression or that there is a secondary response in the kidney to the progressive renal failure. PMID- 1912404 TI - Research on problems of the dialysis patient. PMID- 1912405 TI - Remarks by the recipient of the 1990 Homer Smith Award. PMID- 1912406 TI - Renal aspects of therapy for human immunodeficiency virus and associated opportunistic infections. AB - Patients with human immunodeficiency virus infection and the acquired immunodeficiency syndrome are often treated with a variety of potentially nephrotoxic drugs. This review summarizes the renal, fluid, and electrolyte complications of drugs used to treat human immunodeficiency virus and associated opportunistic infections. The pharmacokinetics of the drugs are also briefly reviewed, and dosing guidelines for the use of these drugs in patients who have renal insufficiency or who are receiving dialysis are provided. PMID- 1912407 TI - Assessing the progression of renal disease in clinical studies: effects of duration of follow-up and regression to the mean. Modification of Diet in Renal Disease (MDRD) Study Group. AB - Many clinical studies of the effects of low-protein and low-phosphorus diets on the course of chronic renal disease have used the rate of decline in renal function to assess the rate of progression. In this report, data from the feasibility phase of the Modification of Diet in Renal Disease Study were used to analyze methods used in other studies. The focus is particularly on the effects of duration of follow-up and of regression to the mean. The findings are summarized as follows. (1) During the mean follow-up period of 14.1 months, rates of decline in glomerular filtration rate, creatinine clearance, and the reciprocal of the serum creatinine concentration were highly variable among individuals, and mean rates of decline were slow. (2) Precision of estimates of individual rates of decline in renal function were relatively low and improved with increasing duration of follow-up. (3) Correlations between rates of decline in creatinine clearance and the reciprocal of the serum creatinine concentration with glomerular filtration rate in individuals were significant but weak and became stronger with increasing duration of follow-up. (4) After entry into the study, mean rate of decline in the reciprocal of the serum creatinine concentration became less negative. The change predicted simply from regression to the mean was 68.4% of the observed change.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1912408 TI - Reversible hexadimethrine-induced alterations in glomerular structure and permeability. AB - Female Munich-Wistar rats received hexadimethrine (HDM) i.v. until the onset of proteinuria (PEAK)--a period of not more than 30 min. There were four experimental groups: C (control), H (HDM only), HH (HDM and heparin), and HHD (identical to HH but with dextran clearances measured). Rats in groups HH and HHD received a heparin bolus after the PEAK period, whereas rats in group H did not. HDM led to dramatic increases in both albumin and IgG excretion. Glomerular filtration rate and renal plasma flow rate were reduced by 30 to 50% after HDM infusion. Neutral dextran clearances for radii greater than 30 A were elevated during the PEAK period, and, concurrently, there was extensive intraglomerular microthrombosis, obliteration of foot processes, and disruption of filtration slit diaphragms. One hour later, glomerular filtration rate, renal plasma flow rate, dextran clearances, and proteinuria returned to baseline in groups HH and HHD but not in group H. Recovery in heparin-treated rats was associated with reversal of HDM-associated morphological alterations. Membrane pore-size parameters calculated from the dextran clearances indicate that HDM leads to a detect in glomerular size-selectivity. The facts that maximal albuminuria tended to precede maximal excretion of IgG and that increases in albumin excretion were proportionately greater than those of dextran or IgG suggest that HDM also leads to a time-dependent defect in glomerular charge-selectivity. PMID- 1912409 TI - Antidiuretic hormone modulates membrane phosphoproteins in toad urinary bladder and retrieved water channel containing apical membrane vesicles. AB - Antidiuretic hormone (ADH) dramatically increases the water permeability of toad urinary bladder by insertion of unique highly selective water channels into the apical membranes of granular cells. Before ADH stimulation, water channels are stored in high concentrations in the limiting membranes of large cytoplasmic vesicles called aggrephores. ADH stimulation causes aggrephore fusion with the granular cell apical membrane and increases water permeability. Transepithelial osmotic water flow causes a rapid attenuation of the ADH-elicited increase in water permeability through a process called flux inhibition. Flux inhibition is due to retrieval of ADH water channels by apical membrane endocytosis. When phosphoproteins of intact bladders are labeled with (32P)orthophosphate, the 32P content of 34-, 28-, and 17-kDa proteins is increased by ADH stimulation. When flux inhibition occurs, the 32P-labelling of a 15.5-kDa protein is reduced to approximately one half its original value (Konieczkowski M, Rudolph SA, J Pharmacol Exp Ther 1985;234:515). These observations have been confirmed, and these studies have been extended, by using a combination of subcellular fractionation and membrane protein chemistry techniques. All four of these phosphoproteins are present in membrane fractions of granular cells. Analysis of membrane proteins by a combination of Triton X-114 partitioning and an alkaline stripping technique reveals that the 28- and 17-kDa species are integral membrane proteins of unknown function. In contrast, the 32P-labeled 15.5-kDa protein is a peripheral membrane protein. It is attached to the cytoplasmic (outer) surface of highly water-permeable vesicles retrieved during flux inhibition.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1912410 TI - Effect of pyridostigmine bromide on serum bromide concentration and the anion gap. PMID- 1912411 TI - Antigen presentation by renal tubular epithelial cells. AB - The interaction between immune effector cells such as T lymphocytes and parenchymal cells in organ-specific immune injury is dynamic. It is now appreciated that the specificity, intensity, and eventual destructive effects of such interactions can be greatly influenced by responses of the target issue. Renal tubular cells are particularly well suited to participate in such immune collaborations. (1) They are exposed to innumerable potentially immunogenic peptides from blood and glomerular filtrate and have pathways to further process these peptides; (2) they express surface molecules which facilitate their engagement to T cells; and (3) they can produce proinflammatory cytokines. In the models of immune-mediated tubulointerstitial injury that are currently studied, there has been a great interest in defining the T lymphocytes that initiate, accelerate, or suppress disease. Surprisingly, there has been relatively little attention on defining the tubular cell responses that regulate these immune mediated processes. This review will therefore focus on this intriguing aspect of immune tubular injury and relate what is known about antigen presentation by tubular cells in autoimmune renal disease. PMID- 1912413 TI - Chronic amphotericin B nephrotoxicity in the rat: protective effect of calcium channel blockade. AB - Amphotericin B is used despite predictable nephrotoxicity because it remains the most efficacious agent currently available for systemic fungal infections. It has been previously shown that calcium channel blockade prevents renal vasoconstriction and blunts the fall in glomerular filtration rate during acute amphotericin B infusion in the rat. Therefore, the effect of cotreatment with diltiazem on nephrotoxicity during chronic daily amphotericin therapy in rats was studied. Rats were given diltiazem (45 mg/kg, 1 h before and 1 h after amphotericin) or vehicle by gastric tube; and amphotericin B (5 mg/kg/day i.p.) for 10 days. Control rats received corresponding vehicles by gastric tube and daily i.p. infection. Renal function was determined 24 h after the last dose of amphotericin or vehicle. Serum creatinine rose significantly in rats receiving amphotericin alone (initial versus final, 0.50 +/- 0.07 versus 1.09 +/- 0.20 mg/dL; P less than 0.05) but not with amphotericin plus diltiazem (0.54 +/- 0.11 versus 0.84 +/- 0.23 mg/dL; P was not significant). Amphotericin rats had a marked decrease in glomerular filtration rate (amphotericin versus control, 0.28 +/- 0.04 versus 1.23 +/- 0.08 mL/min/g kidney wt; P less than 0.05) and renal plasma flow (1.63 +/- 0.19 versus 3.50 +/- 0.40 mL/min/g kidney wt; P less than 0.05). These adverse renal hemodynamic effects were prevented by cotreatment with diltiazem (amphotericin plus diltiazem; glomerular filtration rate, 0.82 +/- 0.18 mL/min/g kidney wt; P less than 0.05 versus amphotericin; P was not significant versus control; renal plasma flow, 3.24 +/- 0.63 mL/min/g kidney wt; P less than 0.05 versus amphotericin; P was not significant versus control).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1912412 TI - Role of countercurrent multiplication in renal ammonium handling: regulation of medullary ammonium accumulation. AB - Ammonium (NH3 plus NH4+), produced predominantly in the proximal tubule, is transferred to the final urine by a process involving countercurrent multiplication of ammonium which generates an ammonium concentration gradient in the renal medulla. It was hypothesized that if urinary ammonium excretion rates are controlled in part by the medullary ammonium gradient, changes in hydration and acid-base state should cause changes in the medullary ammonium gradient consistent with expected changes in urinary ammonium concentrations. To test that hypothesis, rats were subjected to water diuresis, water deprivation, water deprivation plus furosemide, and dietary acid and base loads and corticomedullary ammonium gradients in their kidneys were then measured. Sections were cut along the corticomedullary axis to yield slices of cortex, outer stripe of outer medulla, inner stripe of outer medulla, and three levels of the inner medulla. The total ammonia content of homogenized slices was measured by either a membrane ammonia electrode or an enzymatic technique. Kidneys from water-deprived animals showed a distinct ammonium gradient along the corticomedullary axis, with the highest contents found at the tip of the papilla. The gradient was attenuated by water diuresis and abolished by furosemide. Acid loading enhanced the gradient, and base loading abolished it. These results indicate that the corticomedullary ammonium gradient is regulated in response to changes in hydration and acid-base state. PMID- 1912414 TI - Helicobacter pylori: its epidemiology and its role in duodenal ulcer disease. PMID- 1912415 TI - Helicobacter pylori: causal agent in peptic ulcer. Microbiological aspects. PMID- 1912416 TI - Virulence and pathogenicity of Helicobacter pylori. AB - H. pylori is a highly virulent organism as evidenced by its low infective dose and widespread high prevalence in human populations. Its virulence is achieved through its ability to survive in a moist environment and its massive urease production which allows it to survive in the acidic gastric juice long enough to colonize the gastric mucus. Gastric colonization is facilitated by cell wall associated lectins which permit the bacterium to bind to gastric mucus and the gastric epithelial cell. Once in this location, H. pylori produces several enzymes which may harm the gastric epithelium, particularly urease (through ammonia generation) and phospholipases A and C. H. pylori also weakens the gastric mucous layer by digesting its glycoproteins and lipids, making the mucus less hydrophobic and more water soluble. Helicobacter pylori attracts phagocytic cells, inducing both acute and chronic inflammation as well as an antibody response. Persistence of H. pylori in the mucosa may be enhanced by its cytotoxin and catalase production, by which it survives after phagocytosis by neutrophils. PMID- 1912417 TI - Helicobacter pylori and peptic ulceration: histopathological aspects. PMID- 1912418 TI - Helicobacter pylori therapy: effect on peptic ulcer disease. PMID- 1912419 TI - Helicobacter pylori: causal agent in peptic ulcer disease? Conclusion. PMID- 1912420 TI - Medical treatment of duodenal ulcer: acid inhibition or Helicobacter pylori eradication? AB - To ascertain whether acid inhibition or Helicobacter pylori (HP) colonization is the decisive factor in the healing of duodenal ulcer, we treated 54 patients with famotidine and carried out long-term follow-up. Helicobacter pylori colonization was found in 70.4% of patients before treatment. There were no differences in the pre-treatment characteristics between patients with HP positive or HP negative ulcers. The 4-week and 8-week healing rates after famotidine treatment were 72.5% and 82.4% respectively. No difference in HP colonization was found between patients with ulcer healed and those with ulcer not healed (78.4% vs 64.3% at 4th week and 77.3% vs 71.4% at 8th week, P greater than 0.05). In patients with ulcer healed at 4th week, the intragastric pH was raised significantly and the antral acute inflammation was less severe than those with ulcer not healed. Ulcer recurrence was found in 76.9% of patients within 1 year, but there was no difference in ulcer recurrence between the patients with positive or negative HP colonization at the time of ulcer healing. Our results suggest that duodenal ulcer healing and recurrence are closely related to acid inhibition rather than to HP colonization. PMID- 1912421 TI - Snake skin pattern gastropathy in cirrhotic patients. AB - Gastric mucosal lesions are common in patients with cirrhosis. Among them, snake skin pattern gastropathy (SSPG) is the most distinguishing one. A prospective study was conducted to investigate the incidence of SSPG in cirrhotic patients, the relationship between the degree of portal pressure and SSPG, and the possible association of SSPG with serum levels of gastrin and pepsinogen I. SSPG was found to be significantly more common in 100 cirrhotic patients than in 100 age- and sex-matched healthy controls (41% vs 0%, P less than 0.0001). Hepatic venous pressure gradient and serum gastrin and pepsinogen I levels were measured in 21 cirrhotic patients with SSPG and 25 cirrhotics without SSPG. There was no significant difference in hepatic venous pressure gradient (16.1 +/- 4.4 mmHg vs 16.1 +/- 4.9 mmHg, P greater than 0.05), serum gastrin level (78.0 +/- 26.7 pg/mL vs 80.1 +/- 32.5 pg/mL, P greater than 0.05) and serum pepsinogen I level (69.5 +/- 26.6 ng/mL vs 65.2 +/- 26.1 ng/mL, P greater than 0.05) in cirrhotic patients with or without SSPG. In conclusion, SSPG is common in cirrhotic patients. Portal pressure per se may not be the only factor causing SSPG--other aggressive factors may be needed together to cause the gastropathy. There is no evidence of correlation between serum gastrin or pepsinogen I level and SSPG. PMID- 1912422 TI - Significance of blood flow in the inferior and superior mesenteric veins for the formation of oesophageal varices. AB - The degree of involvement of blood flow in the superior mesenteric vein and inferior mesenteric vein in the formation of oesophageal varices is not known. We have developed a method by which the contributions of these veins to portal blood flow can be evaluated simultaneously in a relatively non-invasive way. An enteric coated capsule containing [123I]iodoamphetamine (IMP) is given by mouth and 3 h later [123I]IMP is instilled into the rectum. The data obtained are treated by computer to calculate the portal shunt index via the inferior and superior mesenteric veins. In chronic hepatitis and cirrhosis, when varices were absent, the difference in these indices was not significant. In the presence of varices, the portal shunt index via the inferior mesenteric vein was significantly higher than that via the superior mesenteric vein. It was suggested that the contribution of blood flow in the inferior mesenteric vein the portal/splenic axis is important in the formation of varices. PMID- 1912423 TI - Hepatolithiasis in East Asia: comparison between Japan and China. AB - The incidence of hepatolithiasis is high throughout East Asia compared with the West, but the marked difference in the relative proportion of hepatolithiasis to all cholelithiasis cases exists even among countries of similar ethnic backgrounds. A retrospective study of cases was conducted in two areas in China with the aim of clarifying the presence of such regional difference in China itself. The relative proportion of hepatolithiasis was 21.2% in Shenyang, 9.2% in Beijing and 4.1% in Fukuoka, Japan. A significant difference in the location of stones was also found between Shenyang, Beijing and Fukuoka. Intra- and extrahepatic hepatolithiasis in all hepatolithiasis cases was 95% in Shenyang and 75% in Beijing. Involvement of both hepatic lobes was found in 73% in Shenyang and less than 60% in the other two, suggesting that hepatolithiasis of the old form or of an advanced stage still lingers in Shenyang. In conclusion, regional differences in the proportion and the type of hepatolithiasis exist in China itself, as well as in the Chinese population in Taiwan, Hong Kong and Singapore, as previously reported. The possible contribution of environmental factors to the occurrence of hepatolithiasis is again emphasized. PMID- 1912424 TI - Aetiology and prognosis of fulminant viral hepatitis in Japan: a multicentre study. The Study Group of Fulminant Hepatitis. AB - In 236 patients with fulminant viral hepatitis (FVH), type B (FBH) was most common (47.5%), followed by non-A non-B hepatitis (FNANB, 44.9%) and hepatitis type A (FAH, 7.6%). The survival rate was significantly higher in the FAH group than in the FBH and FNANB groups (61.1, 36.6 and 18.9% respectively), and was significantly higher in the FBH group than in the FNANB group. In spite of screening for hepatitis B virus (HBV), FBH was prevalent (27 of 41) in post transfusion cases; this phenomenon is discussed in relation to a recently revealed mutation of HBV. Within a month after the onset of hepatitis symptoms all cases in the FAH, 93% in the FBH and 79% in the FNANB group, developed encephalopathy. When the duration of illness before the onset of encephalopathy was more than 10 days (a subacute form), the survival rate was significantly lower than when encephalopathy developed in less than 11 days (an acute form). This difference could be accounted for by the difference in the relative frequency of aetiological viruses in the two forms and the higher survival rate in the acute, than the subacute, form in the FNANB group. PMID- 1912425 TI - Frequency of abnormalities detected by abdominal ultrasound among Japanese adults. AB - Abdominal ultrasound examination was given to 715 (566 male and 149 female) adult non-manual workers in Tokyo as part of their annually required medical check-up. Gross abnormalities were found in 44.5% of males and 34.2% of females. The most common finding was fatty liver (15.2%), seen four times as frequently in males as in females. There were 93 elevated lesions in the gall-bladder in 56 subjects (7.8%); some required follow-up examinations because malignancy could not be excluded. Small cystic lesions were frequently seen in the kidney (6.4%) and in the liver (4.8%). Gallstones were found in 3.4%. Mild splenomegaly occurred in 3.4%. Ten mass lesions, 8 hyperechoic and 2 hypo-echoic, were found in the liver, but subsequent imaging studies showed them to be benign haemangiomas. Other changes found included calcific lesions in the liver (2.1%) and in the spleen (0.4%), renal stones (2.0%), thickened wall of the gall-bladder (3.2%), intramural stones (0.8%) and debris/sludge (0.4%) in the gall-bladder, dilated pancreatic duct (0.7%) and common bile duct (0.3%), liver cirrhosis (0.4%), hydronephrosis (0.1%), enlarged pancreas (0.1%), small pancreas (0.1%), ovarian tumour (0.1%), uterine tumour (0.1%), abnormally shaped kidney (0.1%) and situs inversus (0.1%). It was concluded that abdominal ultrasound is an important examination for a mass screening or a physical check-up commonly practised as the 'human dock' for adults in Japan. PMID- 1912426 TI - Clinical research in gastroenterology: history and future prospects. PMID- 1912427 TI - The Sydney World Congresses of Gastroenterology. PMID- 1912428 TI - Helicobacter pylori and duodenal ulcer. PMID- 1912429 TI - A double-blind study of misoprostol (SC-29333) in the healing of duodenal ulcer. AB - In a double-blind randomized placebo controlled trial, 50 patients with endoscopically confirmed duodenal ulcer were treated with either misoprostol 200 micrograms or placebo in q.i.d. doses for 4-8 weeks. Of 25 patients in the placebo group, four defaulted and two were withdrawn due to worsening of symptoms. Of 25 misoprostol-treated cases, 17 cases (68%) and 21 cases (84%) healed at 4 and 8 weeks respectively, compared with three (14%) and five (24%) of the 21 placebo-treated cases (P less than 0.001). Except for diarrhoea in 2 patients in each group and itching in one with misoprostol, no serious side effects were noted. PMID- 1912430 TI - The Sydney System: a new classification of gastritis. Introduction. PMID- 1912431 TI - The Sydney System: histological division. PMID- 1912432 TI - The Sydney System: endoscopic division. Endoscopic appearances in gastritis/duodenitis. PMID- 1912433 TI - The Sydney System: microbial gastritis. PMID- 1912434 TI - The Sydney System: auto-immune gastritis. AB - The association of gastric auto-immunity with chronic gastritis has been recognized for more than 30 years. Despite this, little is known about the initiation of auto-immune gastric mucosal injury or the role of gastric auto antibodies in this disease process. The current review describes recent progress in our understanding of these fundamental questions on the origin and progression of auto-immune gastritis. In addition, evidence is presented (epidemiologic, clinical, pathologic and experimental) that strongly supports the view that auto immune gastritis is a distinctive category of chronic gastritis with significant long-term sequelae. PMID- 1912435 TI - The Sydney System: epidemiology and natural history of chronic gastritis. AB - Chronic gastritis is a common disease which forms an important background to the pathogenesis of several gastric diseases. In most instances, gastritis seems to be a bacterial (microbial) disease. It begins as long-lasting, chronic inflammatory reaction directed against Helicobacter pylori (HP), or occasionally against other spiral bacteria, which colonize in the space between the surface epithelium and the mucous layer. Gastritis may, irrespectively of the HP-related or HP-independent origin, progress to an atrophy (chronic gastritis with atrophy) in the underlying mucosa. Prevalence of gastritis increases with increase in age, but great variations exist in the age-specific prevalence and in mean age of onset of the gastritis in different populations. A high rate and an early onset of the HP-related gastritis associates with low socio-economic status. Chronic gastritis, and the gastritis with atrophy in particular, may interfere with the function of the affected gastric mucosa, and may subsequently increase or decrease the risk of some gastric diseases, such as cancer and peptic ulcer. Both antral and corpus gastritis with coexistent severe atrophic changes have been shown to be associated with an increased risk of gastric cancer. In addition, gastritis seems to also play an important role in the pathogenesis of peptic ulcer. Virtually all patients with DU and GU have coexisting and preceding gastritis. The cumulative risk of ulcer has been estimated to be high in subjects with gastritis, but, in contrast, to be low in subjects who have normal gastric mucosa. PMID- 1912437 TI - Functional phenotypes of T lymphocytes: adhesion, migration and memory--and suppression? PMID- 1912436 TI - Myo-electrical and motor activity of the stomach in the first days after abdominal surgery: evaluation by electrogastrography and impedance gastrography. AB - The electrical and motor activities of the stomach were studied in the early postoperative phase after abdominal surgery by means of surface recording techniques: electrogastrography (EGG) and impedance gastrography (IGG). EGG and IGG recordings were made pre-operatively and on the first and second postoperative days. Physical signs and symptoms related to gastrointestinal motility were assessed. Two patient groups were studied; a group of patients undergoing cholecystectomy (n = 9) was compared with a group with major colonic surgery (n = 14). After colonic surgery, resumption of a normal oral diet was later and nausea and vomiting were seen more frequently than after cholecystectomy. Other physical signs concerning intestinal motility did not differ between the groups. Gastric myo-electrical activity (0.04-0.06 Hz), recorded electrogastrographically, tended to decrease in the postoperative phase in both groups, and return to pre-operative values later in the colonic surgery group. However, none of the differences reached statistical significance. Abnormal gastric activity (tachyarrhythmia) was observed in one pre-operative patient but in 6 patients (2 cholecystectomy, 4 colonic surgery) after operation. IGG variables were not significantly affected by the operation and were not significantly different between the groups. No correlation between the symptoms nausea and vomiting in the postoperative phase and the incidence of tachyarrhythmias could be demonstrated in this study. It is concluded that antral myo-electrical and motor activity, measured with non-invasive techniques (EGG and IGG), are not grossly abnormal on the first and second postoperative day after abdominal surgery. It is further concluded that abnormal gastric frequencies do not appear to play a major role in the genesis of postoperative nausea and vomiting. PMID- 1912438 TI - Amino acid residues of core region of hepatitis B virus. Asymptomatic carriers versus patients with liver disease. AB - Recent molecular biological studies have shown that mutations of hepatitis B virus (HBV) genes may have an important role in the pathogenesis of HBV-induced liver diseases. It has been suggested that the core antigen of HBV could be an immunologic target of cytotoxic T lymphocytes. In this study, nucleotide sequences encoding 183 amino acid residues of the core region of HBV were analysed in 4 asymptomatic healthy carriers and in 5 patients with chronic liver disease, in whom serum aminotransferase levels were fluctuating. A cluster of amino acid substitutions were found from codon 87 to 97 of the core region of HBV in all 5 patients with liver diseases. Such changes were not found in any of the asymptomatic carriers. These data suggest that the peptide sequence spanning 11 amino acid residues in this particular region may play an important role in the pathogenesis of B-viral liver disease, and could be an immunologic target of cytotoxic T lymphocytes. PMID- 1912439 TI - The Journal of Gastroenterology and Hepatology: the first five years ... and the next. PMID- 1912440 TI - Clinicopathological staging for colorectal cancer: an International Documentation System (IDS) and an International Comprehensive Anatomical Terminology (ICAT). AB - The purpose of tumour staging for colorectal cancer (CRC) is to help define clinical management, facilitate communication between physicians, provide a basis for stratification and analysis of treatment results in prospective studies, and provide some prognostic information for patients and their families. The World Congresses of Gastroenterology, Digestive Endoscopy, and Coloproctology, Working Party on staging for CRC studied six commonly used systems to review their strengths and weaknesses. Although it was concluded that defining a new staging system was unnecessary, it was recognized that there is a need to define a terminology to describe the full anatomic extent of spread of CRC. Furthermore, we note that there are several additional features, derived from both clinical and pathology information, which have had prognostic significance shown by appropriately constructed multivariate analyses and which can be used to formulate a more accurate prognostic index than that provided by a description of anatomical tumour spread. Thus the Working Party came to two principal conclusions. First, a standard format should be adopted for the collection of the essential data required for prospective studies, and we recommend the 'International Documentation System (IDS) for CRC' for this purpose. Second, a nomenclature which describes the full anatomical extent of tumour spread and residual tumour status in CRC has been defined and should be adopted, from which all currently used staging systems can be derived. We have called this nomenclature the 'International Comprehensive Anatomical Terminology (ICAT) for CRC'. In the event that these recommendations are adopted, we envision that there will be improved clarity in the documentation of treatment outcome for patients with CRC and improved communication of results derived from prospective studies. Furthermore, an acceptance of IDS and ICAT would set the scene to develop a prognostic index for individual patients with CRC by the expansion of anatomical clinicopathology staging information to include additional factors which have independent prognostic significance. PMID- 1912441 TI - Influence of glutamine and branched chain amino acids on the jejunal atrophy associated with parenteral nutrition. AB - Infusions of conventional parenteral nutrients (CPN) are associated with gut atrophy. This may be due to the absence of glutamine in such solutions. Although glutamine is a preferred gut nutrient, it is excluded from CPN because it is unstable at room temperature. This problem may be circumvented either directly by the infusion of fresh solutions of glutamine, or indirectly by the infusion of branched chain amino acids (BCAA). We evaluated the effect of infusing either glutamine, BCAA, or glutamine plus BCAA-enriched CPN on the rat jejunum. Sixty male Wistar rats were randomized to receive 6 days of either conventional parenteral nutrition (CPN), CPN plus 1.5% glutamine (GLN), CPN plus 2% BCAA (BCAA), CPN plus 0.8% BCAA and 1.0% glutamine (GLN/BCAA), or a normal oral diet (Chow). Standardized segments of jejunum were then removed for assessment. Compared with the CPN group, both the GLN/BCAA and the BCAA groups had greater mucosal weights (P less than 0.05) and mucosal protein concentrations (P less than 0.05), the GLN/BCAA group had greater jejunal weights (P less than 0.05), and the GLN group had an increased jejunal weight (P less than 0.05) and a higher crypt cell production rate (P less than 0.05). We conclude that the infusion of glutamine or BCAA-enriched parenteral nutrition improves jejunal morphology compared with conventional parenteral nutrition. PMID- 1912442 TI - Structural and functional changes of the gastric mucosa in rats with portal hypertension. AB - Structural and functional changes of the gastric mucosa were studied in rats made portal hypertensive by partially ligating the portal vein. Studies were carried out at either 3 or 12 days after ligation or sham operation. At 3 days, structural changes were greater than at 12 days, the major effects being vascular congestion in the lamina propria, muscularis mucosa, submucosa, and submucosal oedema. Transmission electron microscopy showed only a mild hyperplasia in the muscularis mucosa. Gastric blood flow appeared to decrease at 3 days post ligation compared to sham-operated control rats, but was significantly increased by 12 days after ligation (P less than 0.01). Cardiac output also appeared to increase in the portal hypertensive rats by 12 days post-ligation but this was not statistically significant. Portal venous inflow was significantly increased by 12 days (P less than 0.05) but after correction for collateral circulation liver blood flow had returned to normal values by 12 days post-ligation. PMID- 1912443 TI - Upper and lower gastrointestinal endoscopy in children and adolescents with Crohn's disease: a prospective study. AB - Fifty-six children and adolescents with Crohn's disease were prospectively investigated with gastroscopy and colonoscopy irrespective of localizing symptoms or signs. Routine biopsies were taken from endoscopically normal and abnormal areas. A high incidence (71%) of upper gastrointestinal (GI) involvement was found. In 41%, these findings were instrumental in making the diagnosis. The ileum was viewed in 49 of the 56 cases. Overall, the upper GI tract was involved in 71%, the terminal ileum in 53%, and the colon in 86% (oesophagus 16%, body of stomach 46%, antrum 36%, duodenum 21%, terminal ileum 53%, caecum 69%, transverse colon 71%, sigmoid 60% and rectum 41%). Upper and lower gastrointestinal endoscopy with systematic biopsies should be performed early in the diagnostic assessment of children and adolescents with suspected inflammatory bowel disease to enable accurate diagnosis and assessment of extent of disease. PMID- 1912444 TI - Cystic disease of the liver following prenatal and perinatal exposure to aflatoxin B1 in rats. AB - Experiments were designed to elucidate the differences, if any, in the liver histology induced by aflatoxin B in newborn and adult animals. The transfer of toxic metabolites from pregnant rats to their litters was confirmed by thin layer chromatography of liver homogenates in the latter. Extensive cystic lesions of the biliary and hepatic type developed only in young animals. Multifocal hepatic necrosis, bile ductular proliferation, areas of altered hepatocytes, neoplastic nodules and hepatocellular carcinoma constituted the total spectrum in both adult and newborn animals. Increased susceptibility to the toxins early in life appears to be responsible for this intriguing phenomenon. These aspects may have a bearing on the genesis of childhood liver disease. PMID- 1912445 TI - Trimethadione tolerance test for the quantitative assessment of liver function in rats. AB - The quantitative estimation of the hepatic functional volume in rats was attempted using the serum dimethadione (DMO)/trimethadione (TMO) ratio in a single blood sampling after oral administration of TMO, which we call the TMO tolerance test, in order to develop a means of pre-operatively assessing hepatic resectability. Serum DMO/TMO ratios correlated well with the total amount of the hepatic microsomal TMO-N-demethylase activity (enzyme activity) and with the remnant liver weight after 37% and 68% partial hepatectomy. These ratios increased after partial hepatectomy in parallel with the changes in the enzyme activity and the remnant liver weight. The results suggest that the quantitative functional changes of the remnant liver after hepatectomy in both CCl4-treated and untreated rats can be estimated pre-operatively by the TMO tolerance test. PMID- 1912446 TI - Diagnostic utility of ultrasonography in hepatic venous outflow tract obstruction in a tropical country. AB - The present study was undertaken to define the role of ultrasonography (US) in screening and diagnosis of hepatic venous outflow tract obstruction. Forty-five consecutive patients clinically suspected to have hepatic venous outflow tract obstruction were included in the study for screening by US and for assessment of patency or block in the hepatic vein (HV) and/or inferior vena cava (IVC). Four patients were excluded from the study. Eleven patients had a diagnosis other than hepatic venous outflow tract obstruction and all these patients were found to have patent HV and IVC. Thirty patients were finally diagnosed to have hepatic venous outflow tract obstruction. Using US, as a screening test 27 (90%) out of 30 such cases were correctly identified as cases of hepatic venous outflow tract obstruction and in these cases the site of block in hepatic venous outflow tract (major HV and/or IVC) was correctly diagnosed in 90% of the cases. Our results indicate that US is a sensitive and accurate test and should be the initial investigation for screening and identifying the site of obstruction in patients with hepatic venous outflow tract obstruction. PMID- 1912447 TI - Hepatitis B vaccination: half dose recombinant DNA hepatitis B vaccine (B-Hepavac II) is as immunogenic as the full recommended dose in healthy adults. AB - Sixty-seven healthy adult volunteers aged 20-40 years with no previous exposure to hepatitis B virus were randomized to receive either a 10 micrograms or 5 micrograms dose of recombinant DNA hepatitis B (HB) vaccine (B-Hepavac II) intramuscularly at 0, 1 and 6 months. Two months after the third injection 100% of subjects had seroconverted: 97% of the 10 micrograms group and 91% of the 5 micrograms group had antibody to HB surface antigen (anti-HBs) levels greater than 10 iu/L. The geometric mean titres (GMT) of anti-HBs levels at this time were 891 iu/L in the 10 micrograms dose group and 923 iu/L in the 5 micrograms dose group. These differences were not significant. Adverse effects included fever and mild pain at the injection site. The reduced dose of 5 micrograms was as effective as the standard 10 micrograms dose. PMID- 1912448 TI - Pathological and laboratory findings in LEC/Otk rats that spontaneously develop hepatic injury. AB - The LEC strain of rats that spontaneously develops hepatic injury has been introduced into specific pathogen-free (SPF) conditions (SPF-LEC/Otk). The present communication describes the clinical and pathological features of the SPF LEC/Otk rats. The characteristic features of these animals are as follows: (i) Jaundice develops in almost all rats with increase in the P-GPT level; (ii) The animals show episodes of jaundice, a high P-GPT level and liver cell necrosis, but only slight inflammatory cell infiltration; (iii) The liver cells show characteristic microvesicular fatty changes; (iv) The P-GPT level shows increases, first at 18 weeks and then at 25 weeks of age; (v) The rats show immunological disorders, such as deficiency of immunoglobulins, especially IgG1, and of helper T cells; (vi) Infectious agents such as viruses do not seem to be involved, although this possibility cannot be absolutely excluded; (vii) The immunological disorders are not directly associated with the occurrence of liver cell necrosis; and (viii) The pattern of inheritance (autosomal single-recessive trait) of the disease strongly suggests that it is due to a genetic metabolic disorder. PMID- 1912450 TI - Growing cavernous haemangioma of the liver: 11-fold increase in volume in a decade. AB - A 57 year old Japanese male was incidentally found to have a 7.5 cm diameter hepatic haemangioma. Eleven years later he was operated on because the haemangioma had grown into a 17 cm mass causing upper abdominal fullness. Volumetry on computerized tomograms disclosed that the haemangioma had grown from 123 cm3 to 1343 cm3 in volume. Quantitative documentation on growing hepatic haemangioma has been rare. PMID- 1912449 TI - A new classification of cystic malignant tumours of the liver: classification of 65 cases reported at the 26th annual meeting of the Liver Cancer Society of Japan. PMID- 1912451 TI - Neuronal mechanisms of motor learning in mammals. AB - Neural mechanisms subserving the acquisition of new motor skills are discussed in this article. Motor learning is defined, in this context, as the acquisition of novel motor skills. It is proposed that complex motor skills are acquired through a process of segmental motor learning, in which movement segments are formed, and retrieved for the execution of the learned skill. Individual movement segments are created by modulating neural activity in loop circuits that link the motor cortex and the periphery. This neural modulation occurs through synaptic plasticity in the motor cortex. Increase of synaptic efficacy in existing neural circuits, in the form of long-term potentiation (LTP), is proposed to be involved in earlier stages of motor learning. It is suggested that the retention of motor skills involves formation of new synapses. PMID- 1912452 TI - Paucity of dorsal inspiratory neuron collateral projections to ventral inspiratory neurons. AB - The inspiratory region of the ventral respiratory group was mapped in six Nembutal anaesthetized cats. Records multi-unit activity were taken in five or six locations at 0.5 mm spacings. These locations were then used as stimulating sites to test for the antidromic activation of 40 bulbospinal, inspiratory neurons recorded in the ipsilateral, dorsal respiratory group. Only four (10%) were antidromically activated. In a single anatomical experiment, rhodamine labelled microspheres were injected into the ventral group, and Flurogold was injected into the contralateral spinal cord. No neurons in the dorsal group were found to be double-stained. It was concluded that, ipsilateral collaterals from inspiratory dorsal group neurons to the inspiratory region of the ventral group are rare. PMID- 1912453 TI - MK-801 fails to modify the effect of methamphetamine on dopamine release in the rat striatum. AB - The effect of MK-801 at a dose of 0.5 mg kg-1, i.p., on methamphetamine-induced (MAP; 4 mg kg-1, i.p.) dopamine (DA) release was examined in the striatum of freely moving rats using an in-vivo microdialysis method. Combined treatment of MK-801 with MAP did not modify the MAP-induced increase in extracellular DA levels or the decrease in 3,4-dihydroxyphenylacetic acid levels. These findings suggest that MK-801 fails to modify the acute effect of MAP on DA release in the striatum. The blocking effect of MK-801 on the development of MAP-induced behavioral sensitization is unlikely to be mediated by DA neurons. PMID- 1912454 TI - Intracellular free calcium in isolated vestibular hair cells and potassium iontophoresis. AB - The resting free calcium level was measured in 128 isolated mammalian vestibular sensory cells using the calcium-sensitive dye fura-2. Iontophoresis was used to apply short, localised and limited pulses of K+ which evoked dynamic changes in intracellular free calcium concentration. While most of the type I hair cells tested showed brief reversible and specific calcium responses, some were unresponsive. The changes in intracellular free calcium were also measured by videomicroscopic analysis. Iontophoretic application of K+ ions is shown to be a suitable method for inducing fast, transient changes in intracellular free calcium in vestibular hair cells. This technique could be useful for applying several ions and charged molecules such as amino acids in in-vitro cellular methods. PMID- 1912455 TI - Restricted diffusion and stability of carbachol-fluorescent nanospheres in-vivo. AB - Mapping neuronal populations that induce behavioral state changes after pharmacological activation requires discrete localization of drug injection sites, and is limited by widespread diffusion of molecular drugs. Nanospheres with diameters of 50-100 nm can reduce diffusion significantly because of their relatively large sizes. The cholinergic agonist carbachol was radiolabeled with methyl14C and incorporated within a latex nanosphere delivery system (LNDS). We quantitatively compared diffusion of 14C-carbachol within these nanospheres with that of free 14C-carbachol, demonstrating approximately ten-fold reduced radial diffusion by nanospheres 10 min to 24 h post-injection; approximately 90% of injected radioactivity was restricted to regions within approximately 100-150 microns and 1400-1500 microns respectively. Thus, incorporation of active agents such as drugs within nanospheres dramatically increases the precision of their delivery in-vivo (here about 1,000-fold by volume). PMID- 1912456 TI - Regional induction of c-fos mRNA by NMDA: a quantitative in-situ hybridization study. AB - The regional expression of c-fos mRNA following acute NMDA administration has been mapped by quantitative in-situ hybridization using 35S-c-fos DNA probe. NMDA induced expression of c-fos mRNA is discrete, largely restricted to the dentate gyrus of the hippocampus and piriform cortex. This distribution is different from the much more widespread distribution of NMDA receptors detected by ligand autoradiography. Expression of c-fos mRNA induced by 225 mg kg-1 NMDA was stereospecifically blocked by pretreatment with the NMDA receptor/ionophore complex blocker, MK-801. Larger doses of NMDA (greater than 175 mg kg-1) were needed for increased expression of c-fos mRNA. Animals which had seizures after acute NMDA administration always had high levels of c-fos mRNA, but equally high levels of c-fos mRNA expression were found in some seizure-free animals. Thus overt seizure activity may not be necessary for c-fos mRNA expression. PMID- 1912457 TI - A Newtonian model of perceptual distortion in visuo-spatial neglect. AB - We propose a simple mathematical model that describes how unilateral brain damage distorts the representation of length in two-dimensional space. The model was tested on eighteen normal adults and six patients with left visuo-spatial neglect after right hemisphere lesion. The subjects bisected lines at eight orientations from vertical to horizontal and the displacement of their transections from true centre was expressed as a function of inclination. Although accuracy differed considerably from patient to patient, sinusoidal functions of the predicted form were found in all cases. The pattern of distortion is an exaggeration of one subtype of normal performance, and is fully consistent with the hypothesis that the cerebral hemispheres have antagonistic attentional biases. PMID- 1912458 TI - Muscle as the primary site for testosterone to promote survival of axotomized motoneurons. AB - Whether the effect of testosterone to promote neuronal survival is expressed through its interaction with motoneurons or with effector muscles was investigated, since androgen receptors are present in both tissues. Following unilateral transection of the hypoglossal and facial nerves, hydroxyflutamide, an androgen receptor antagonist, was injected into the tongue muscles to block androgen receptor binding during the period when rats were treated with testosterone. The results indicate that hydroxyflutamide abolished testosterone effects on the hypoglossal but not the facial motor nucleus, indicating that androgen receptors in effector muscles are the primary mediators of hormonal actions. We postulate that testosterone may play a role in the production of muscle-derived factors which promote the survival of injured motoneurons. PMID- 1912459 TI - Differential response of Apis mellifera acetylcholinesterase towards pirimicarb. AB - The kinetic analysis of Apis mellifera acetylcholinesterase inhibition by the carbamate pirimicarb showed that native and detergent-solubilized membrane enzyme exhibited slightly different carbamylation kinetics. The acetylcholinesterase form sensitive to phosphatidylinositol-specific phospholipase C (PI-PLC) was carbamylated more rapidly (kapp = 36.4 X 10(-3) min-1) than the PI-PLC-resistant counterpart (kapp = 10.13 X 10(-3) min-1) which had a behavior close to that of the soluble tryptic enzyme (kapp = 11.89 X 10(-3) min-1). A difference in acetylcholinesterase sensitivity towards pirimicarb was also observed between foraging and emerging bees. These results show that the molecular structure, the mode of preparation and the source of acetylcholinesterase from the bee head should be taken into account in accurate toxicological studies. PMID- 1912460 TI - Evidence that L-arginine possesses proconvulsant effects mediated through nitric oxide. AB - Increasing evidence suggests a neurotransmitter role for NO in the mammalian CNS. We have now studied the behavioural and electrocortical (ECoG) profile of rats injected into the lateral cerebral ventricle (ICV) with L-arginine (L-arg), the endogenous donor of the guanidino group from which NO physiologically originates. Rats treated with L-arg (up to 300 micrograms) showed behavioural stimulation, ECoG desynchronization with occasional isolated high voltage spikes but not motor seizures. In rats receiving a subconvulsive dose (0.5 microgram) of N-methyl-D aspartic acid, (NMDA; ICV) the microinjection of L-arg (300 micrograms; 1 min before) resulted in behavioural and ECoG seizures. The latter effects were prevented by co-administrating L-arg with N-nitro-L-arginine (L-NAME), an inhibitor of NO synthesis. In conclusion, L-arg possesses proconvulsant effects probably mediated by an increase in NO synthesis. PMID- 1912461 TI - Alteration of calcium influx in rat cortical synaptosomes by soman. AB - Poisoning by soman causes changes in brain activity leading to neuronal death in several brain areas. We investigated whether disruption of normal Ca2+ homeostasis was sufficient to account for at least some of the OP-induced neurotoxicity. Beginning 24 h after a challenge with soman (1 or 4 LD50) K(+) stimulated synaptosomal Ca2+ influx was significantly elevated above that in control animals. Neuronal Ca2+ influx remained elevated for two days after 1 LD50 of soman and at least 7 days after 4 LD50. The effect was specific for depolarization induced influx as there was no effect on resting (5 mM K+) Ca2+ accumulation. These results suggest that increased intracellular Ca2+ may contribute to the neuronal degeneration and neurotoxicity observed after poisoning with soman. PMID- 1912462 TI - Convergent inputs to neurones in the nucleus paragigantocellularis lateralis in the cat. AB - Extracellular recordings were made in the nucleus paragigantocellularis (PGL) of the cat in response to stimulation of the hypothalamic perifornical defence area (HPDA), dorsal periaqueductal grey matter (PAG), nucleus raphe obscurus (Rob), deep peroneal nerve (DPN), and superficial peroneal nerve (SPN). Stimulation of the HPDA, dorsal PAG and SPN evoked excitatory responses whilst the prevalent response to stimulation of Rob was inhibition. However, most of the defence reaction-related neurones showed little response to stimulation of DPN. Of 53 cells tested 48 (91%) received convergent inputs from two or more sites of stimulation. These findings are discussed in relation to the integrative function of PGL in cardiovascular control. PMID- 1912463 TI - Disappearance of leftward rapid eye movements during sleep in left visual hemi inattention. AB - Contrasting hypotheses have been proposed about the functional equivalence between waking saccades and REMs. Patients with left visual hemi-inattention showed dissociation between the direction of waking saccades and that of REMs. REMs directed toward the left were virtually absent, while waking inspective saccades directed in both lateral directions were present, but confined to the right hemispace. It is concluded that: a) the cortical areas regulating attention are relevant in the production of REMs; b) two separate attentional mechanisms have to be considered in relation to the hemi-inattentive syndrome, one is involved in the cognitive control of visual exploration and plays little or no role in the modulation of REMs, the other deals with REMs during sleep and with reflex-like orienting responses to peripheral stimuli during waking. PMID- 1912464 TI - The role of the right parietal region in a movement time estimation task. AB - Thirteen right-handed male students performed a time estimation task by pressing a button with their left or right hand for an interval of either 0.5 or 1.3 s. Thirty channels of EEG were recorded, with the right ear as reference. After transforming the raw EEG data into local average reference data, the topography of event related desynchronization (ERD) of the rhythm within the 10-12 Hz frequency band was studied by computing ERD maps separately for accurate and inaccurate performance. Statistical comparison of ERD maps for accurate and inaccurate movement (Wilcoxon test) resulted in significant differences for the right parietal region prior to movement onset, with a larger ERD before accurate movement. PMID- 1912465 TI - Mechano- and thermo-sensitivity in rats genetically prone to developing neuropathic pain. AB - By selective breeding, lines of rats were derived which consistently expressed high (HA) or low (LA) levels of autotomy following sciatic nerve injury, autotomy being a behavior pattern presumed to reflect the presence of neuropathic paraesthesias and pain. We report here that intact (unoperated) HA and LA rats differ in their responsiveness to cutaneous mechanical and thermal stimuli. Thus, the autotomy trait, which was identified by its expression under conditions of nerve injury, shares determinants with sensory processing channels in the intact animal. PMID- 1912466 TI - pH-lactate dissociation during anoxic insult: taurine effect. AB - Taurine, a sulfur amino acid abundant in brain of the fetus and early day neonate, has been postulated to play a major role in mediating the immature brain's unusually high buffering ability for lactic acidosis reported previously. In this study, we directly investigated this 'taurine effect' using a 10-day-old rat pup model and multinuclear (31P and 1H) nuclear magnetic resonance (NMR) in vivo spectroscopy. Brain of taurine-supplemented pups exhibited significantly higher acid buffering ability against lactic acidosis than age-matched control pups. The study supports the hypothesis that high levels of free cytosolic taurine increase the brain's ability to buffer against lactic acidosis. PMID- 1912467 TI - Unmasking of visual deficits following unilateral prestriate lesions in man. AB - The primate visual cortex is a mosaic of different areas which are roughly organized into two major pathways, a dorsal one along an occipito-parietal channel and a ventral one along an occipito-temporal channel. It is known that visual stimuli are processed differently within these two systems and one might expect therefore that behavioral deficits would differ according to the channel damaged by cerebral lesions. Two patients with left prestriate lesions presented perceptual deficits in the right visual field. These deficits involved reading, recognition of line drawings and colour perception and would be compatible with a dysfunction of the ventral system. Magnetic resonance imaging analysis confirmed that this was the case. PMID- 1912468 TI - Cognitive enhancing actions of PD123177 detected in a mouse habituation paradigm. AB - The anxiolytic-like and cognitive enhancing potential of PD123177, a non-peptide with selectivity for the angiotensin II-2 receptor recognition site, was assessed in a mouse light/dark aversion test and habituation test, respectively. PD123177 (0.01 ng kg-1 to 1.0 mg kg-1 i.p.) failed to alter the behavioural repertoire of animals in the light/dark aversion test. In contrast, daily administration of PD123177 (10.0 ng kg-1 i.p. b.d.) enhanced the performance of mice in a habituation test. In addition, PD123177 overcame the cognitive impairment induced by the administration of scopolamine (0.25 mg kg-1 i.p.). Such findings indicate for the first time a functional role for the angiotension II-2 receptor and further implicate the angiotensin system in the modulation of cognitive processes. PMID- 1912469 TI - The dentate nucleus is a short-latency relay of a primary auditory transmission pathway. AB - Recordings of unit activity showing 4-6 ms latency responses to a click stimulus provided evidence that the dentate nucleus could function as a short-latency auditory relay. On the basis of these findings, plus fiber fillings from injections of phaseolus leucoagglutinin into the dentate, a new auditory pathway between dorsal and ventral cochlear nuclei, dentate nucleus, and rostral thalamus is proposed. The pathway could provide direct, short-latency transmissions to the motor cortex that bypass the classical auditory receptive cortex. PMID- 1912470 TI - Estrogen increases axodendritic synapses in the VMN of rats after ovariectomy. AB - Low doses of estrogen (E) were given to ovariectomized (OVX) rats and the ventromedial hypothalamic nucleus (VMN) was examined at the ultrastructural level. Administration of 10 micrograms of E for two consecutive days resulted in an increase in the number of axodendritic synapses in the VMN in comparison to OVX rats treated with oil. The percentage of axospine and multiple synapses and the length of the postsynaptic density were unchanged by E treatment. These results provide further support for the ability of low doses of E to alter neuronal morphology. PMID- 1912471 TI - Differential effects of M2 and M3 muscarinic antagonists on the sleep-wake cycle. AB - To study the role of muscarinic receptor subtypes in sleep control, methoctramine (25, 50, 75 micrograms), a highly selective M2 antagonist, was injected intra cerebroventricularly into freely moving rats. Methoctramine induced a dose dependent increase in desynchronized sleep (DS) latency (from 62.7 +/- 10 min following saline to 122.4 +/- 13.8 min with the lowest dose) and a 75% decrease in the amount of DS in 6 h recordings. 4DAMP (a M3/M1 selective antagonist) did not significantly change DS latency and percentage time, but it reduced wakefulness (from 38 +/- 2.8% following saline to 25.3 +/- 3.7% with a dose of 2.5), and increased slow wave sleep. The results suggest that M2 muscarinic receptors play a selective role in DS physiology. PMID- 1912472 TI - Input-specific induction of long-term depression in Ca(2+)-chelated visual cortex neurons. AB - An input-dependent increase in postsynaptic Ca2+ may play a role in long-term potentiation (LTP) of synaptic transmission while no or subthreshold increase in Ca2+ is associated with long-term depression (LTD) in the developing visual cortex. To see whether LTD is induced only at tetanized synapses, a Ca(2+) chelator was injected into layer 2/3 neurons in cortical slices from young rats, and excitatory postsynaptic potentials (EPSPs) of these cells, after test stimulation of the white matter and layer 1/2, were observed before and after tetanic stimulation of the former site. The chelator injection led to LTD of EPSPs at tetanized synapses, but no changes were seen at non-tetanized synapses. These results suggest that tetanic inputs induce LTD at tetanized synapses when they are associated with no or subtle increase in postsynaptic Ca2+. PMID- 1912473 TI - Discrimination of motion direction in perimetrically blind fields. AB - Three patients with bilateral and two with unilateral striate cortex lesions have been tested for their ability to discriminate motion direction within their perimetrically blind field. No optokinetic nystagmus could be recorded in any of the three cases of cortical blindness, but all the patients could discriminate with a high level of success between two opposite directions of movement (at least along the horizontal plane) in a forced-choice indication task. In contrast, the two hemispherectomized patients remained at chance level in the same task. This indicates that the residual capacities observed in the patients with occipital lesions depend upon cortical structures. According to neurophysiological findings, the most likely substrate would be the homologue of area MT of the monkey. PMID- 1912474 TI - Chronic nicotine exposure enhances cutaneous axon reflexes in the rat. AB - The effect of chronic nicotine exposure on the cutaneous neurogenic flare response was investigated non-invasively in rats. Axon reflexes were evoked by transdermal iontophoresis of acetylcholine, and resultant changes in skin microvascular blood flux were measured by laser Doppler flowmetry. Rats given five injections of nicotinesulphate (1 mg kg-1 i.p.) daily for 14 days were compared to saline-injected littermates. Axon reflexes were enhanced by 143% after 7 days exposure to nicotine, and by 336% after 14 days exposure. Controls did not display these increases. Axon reflexes measured 7 days after nicotine cessation were similar to pre-nicotine levels. These results may suggest that nicotinic cholinoceptors on skin nociceptors and primary afferents upregulate in response to chronic nicotine exposure, and return to normal following nicotine cessation. PMID- 1912475 TI - Selective inhibition by systemic lidocaine of noxious evoked activity in rat dorsal horn neurons. AB - The effect of systemically injected lidocaine (3-4 mg kg-1) on the responses to noxious and non-noxious stimuli on 28 wide dynamic range (WDR) neurons in the dorsal horn was studied in anesthetized and curarized rats. It was consistently found that lidocaine reduced or suppressed the responses to noxious stimuli whereas it did not act on the responses to non-noxious stimulation and on the spontaneous activity. Furthermore the noxious stimuli were completely ineffective from 10-15 min following the lidocaine injection while the non-noxious stimuli maintained their efficacy. The control responses, in all the cases, returned within 20 min. The results suggest that lidocaine exerts a selective inhibitory effect on nociceptive transmission at the spinal level. PMID- 1912476 TI - Synapses in developing cingulate and hippocampal cortices in undernourished rats. AB - Differential patterns of developmental changes were observed between 10 and 150 days of age in numerical densities of ethanolic-phosphotungstic acid stained synapses in the molecular layer of cingulate cortex (area 29 c,d) and hippocampus (CA1)-dentate region in rat. Chronic caloric undernutrition commencing prenatally caused considerable reduction of synaptic densities up to 45 days of age in both the cortices, but showed opposite trends subsequently; the density attained was higher than control in the cingulate area, but lower than control in hippocampus dentate area. Post-weaning rehabilitatory nutrition resulted in a reduced deviation from normal in the cingulate area but not in the hippocampus-dentate area. PMID- 1912477 TI - Localization of CD44 (P80) on the external surface of a human astrocytoma cell. AB - A brain antigen, originally identified by a MAb 44D10, has been shown to be a glycoprotein with an Mr of 80 kDa. Cellular localization studies of sections of brain showed that the antigen was associated with the membrane of astrocytes. In the present study we demonstrate its localization to the membrane of an astrocytoma cell line by fluorescence and electron microscopic immunogold methods. Heavy labelling with immunogold was found along cellular processes. Labelling of the smooth surfaces of cells and the microvilli was also observed. PMID- 1912478 TI - Novel effects of MPTP: MAO-B unrelated opioidergic activity in mice. AB - The presence of opioidergic activity after i.p. injection of N-methyl-4-phenyl tetrahydropyridine (MPTP) has been investigated in albino mice by studying analgesia and the Straub reaction. MPTP (6.25-25 mg kg-1) produced a dose-related analgesic response and Straub reaction. These effects of MPTP were effectively antagonized by prior naloxone treatment but remained unaffected after the MAO-B inhibitor deprenyl. MPTP thus possesses significant opioidergic activity and this, unlike its neurotoxic actions, does not appear to be dependent on oxidative conversion to MPP+ (1-methyl-4-phenyl pyridinium). PMID- 1912479 TI - Gonadotropin releasing hormone (GnRH)--a novel olfactory stimulant in fish. AB - The aim of this study was to elucidate the putative role of the gonadotropin releasing hormone (GnRH or LHRH) as an olfactory stimulant in fish. We report for the first time extreme sensitivity of the olfactory organ in the rainbow trout (Oncorhynchus mykiss) to GnRH. Recordings of the electroolfactogram (EOG) showed an electrophysiological response to 10(-16) M GnRH four times the amplitude of the response to a fresh water control stimulus. By stimulating the olfactory epithelium with several GnRH analogs and fragments of the decapeptide, the biologically active region of GnRH could be partly elucidated. The response profile of GnRH differed from that of the positive control odorant L-alanine, suggesting that separate receptors or receptor cells are involved. We propose that this potent odorant may act as a reproductive pheromone in fish. PMID- 1912480 TI - Evidence that matrix recognition contributes to stabilization but not induction of LTP. AB - Slices of hippocampus were incubated with Arg-Gly-Asp (RGD) peptides known to block members of the integrin class of matrix receptors. Though the peptides caused no detectable difference in the amount of long-term potentiation (LTP) expressed in the CA1 field 1-2 min after induction with high frequency stimulation, they did produce a reversible, dose dependent decay of LTP over a period of 40 min. This effect was not obtained with various non-RGD control peptides. These results suggest that stabilization of LTP requires adhesive interactions via specific matrix recognition sites, whereas induction and expression do not. PMID- 1912481 TI - Age-related differential expression of neuropeptide mRNAs in Aplysia. AB - The basis of aging in the Aplysia nervous system is unknown. We now report age related changes in mRNA expression of phe-met-arg-phe-NH2 (FMRFamide) and egg laying hormone (ELH) in the abdominal ganglion, a part of the CNS, in young, mature and old Aplysia. Northern blot analysis revealed two mRNA species of 1.4 and 3.2 kb for RMRFamide and a single mRNA species of 0.8 kb for ELH. FMRFamide mRNA level increased 1.5-fold from young to mature and then decreased 3-fold in old animals. ELH mRNA gradually increased between young and mature animals and then escalated 25-fold in old animals. Age differentially affected the mRNA of these two peptides, which may contribute to behavioral changes previously reported. PMID- 1912482 TI - Fos expression in GHB-induced generalized absence epilepsy in the thalamus of the rat. AB - Using the model of gamma-hydroxybutyrate (GHB)-induced generalized absence epilepsy, the present work investigated the distribution of fos oncoprotein expression in the rat thalamus with fos antibody immunohistochemistry. Thirty minutes after absence-like seizures, some fos-immunoreactive cell nuclei were found in bilateral thalamic paraventricular nuclei (PV). After a further 30 min, a massive bilateral induction of fos was observed in the lateral habenular nucleus (LHb), the PV, the rhomboid thalamic nucleus, and the intralaminar nuclei of the thalamus. These results suggest that the LHb and the midline and intralaminar thalamic nuclei may very likely be involved in the pathophysiology of absence seizures. PMID- 1912483 TI - Establishment of chronic intravenous drug self-administration in the C57BL/6J mouse. AB - A wide variety of drugs that have significant human abuse potential have been demonstrated to function as positive reinforcers in animals. The present study was designed to characterize a new mouse model of chronic intravenous drug self administration. Adult male C57BL/6J mice, implanted with external jugular infusion catheters, were given access to response-contingent injections. They did not initiate responding for saline delivery, whereas the C57BL/6J mice initiated morphine, cocaine, methamphetamine and pentobarbital self-administration. Drug maintained responding was consistently and significantly higher for each compound than for saline responding. In contrast to C57BL/6J mice, DBA/2J mice failed to initiate cocaine self-administration. Thus, chronic intravenous drug self administration procedures can be adapted to the inbred mouse. PMID- 1912484 TI - Whole cell recording and conductance measurements in cat visual cortex in-vivo. AB - Long and stable recordings of post-synaptic, action and membrane potentials from visual cortical neurons in-vivo, are possible with the patch-clamp technique. These are comparable to the whole-cell configuration, but with an incomplete seal. EPSPs and IPSPs of normal time course and up to several mV can be recorded. DC potentials ranged from - 30 to - 60 mV and input resistances from 50 to 150 M omega. Injected currents have the same effect as if applied intracellularly. Membrane conductance after electrical stimulation of the lateral geniculate nucleus is increased during the first 20 ms, but decreases from 60 to about 130 ms, during return of the membrane potential to its resting level. The recording method is compared to other intracellular recording techniques in-vivo and in vitro. PMID- 1912485 TI - Synaptic noise and the cross-correlation between motoneuron discharges and stimuli. AB - Theoretical analysis of motoneuron models predicts that the cross-correlogram between motoneuron discharges and stimuli should reflect the derivative of the post-synaptic potential (PSP) in the absence of synaptic noise. The cross correlogram peaks become wider if the amplitude of the noise is significant. To deal with this case, the linear combination of the PSP and its first derivative has been proposed as an approximation. The synaptic noise was regarded as a Gaussian stochastic process (its diffusion approximation), and the estimation of the cross-correlation function for this case is presented. The results were found to be in agreement with reported experimental data. A comparison was made with the linear combination approximation and with the reported computer simulation. PMID- 1912486 TI - Isolation and sequence analysis of a cDNA clone for a carrot calcium-dependent protein kinase: homology to calcium/calmodulin-dependent protein kinases and to calmodulin. AB - Recently, a novel type of calcium-dependent protein kinase (CDPK) that requires neither calmodulin nor phospholipids for activation, has been described in plants. We have isolated a cDNA clone for carrot CDPK by probing a library of somatic embryo cDNAs with oligonucleotides corresponding to highly conserved regions of protein kinases. The product of this gene overexpressed in Escherichia coli reacted strongly with monoclonal antibodies to soybean CDPK. The deduced amino acid sequence of carrot CDPK reveals two major functional domains. An N terminal catalytic domain with greatest homology to calcium/calmodulin-dependent protein kinase type II from rat brain is coupled to a C-terminal calcium-binding domain resembling calmodulin. These features of the primary sequence explain how CDPK binds calcium and suggest a model for CDPK regulation based on similarities to animal calcium/calmodulin-dependent protein kinases. PMID- 1912487 TI - Water deficit modulates gene expression in growing zones of soybean seedlings. Analysis of differentially expressed cDNAs, a new beta-tubulin gene, and expression of genes encoding cell wall proteins. AB - Transfer of soybean seedlings to low-water-potential vermiculite (psi w = -0.3 MPa) results in a reversible decrease in hypocotyl growth and modulation of several polysomal mRNAs (Plant Physiol 92: 205-214). We report here the isolation of two cDNA clones (pGE16 and pGE95) which correspond to genes whose mRNA levels are increased, and one cDNA clone (pGE23) which corresponds to a gene whose mRNA level is decreased in the hypocotyl zone of cell elongation by water deficit. In well-watered seedlings mRNAs hybridizing to pGE16 and pGE95 are most abundant in mature regions of the seedling, but in water-deficient seedlings mRNA levels are reduced in mature regions and enhanced in elongating regions. RNA corresponding to soybean proline-rich protein 1 (sbPRP1) shows a similar tissue distribution and response to water deficit. In contrast, in well-watered seedlings, the gene corresponding to pGE23 was highly expressed in the hypocotyl and root growing zones. Transfer of seedlings to low-water-potential vermiculite caused a rapid decrease in mRNA hybridizing to pGE23. Sequence analysis revealed that pGE23 has high homology with beta-tubulin. Water deficit also reduced the level of mRNA hybridizing to JCW1, an auxin-modulated gene, although with different kinetics. Furthermore, mRNA encoding actin, glycine-rich proteins (GRPs), and hydroxyproline-rich glycoproteins (HRGPs) were down-regulated in the hypocotyl zone of elongation of seedlings exposed to water deficit. No effect of water deficit was observed on the expression of chalcone synthase. Decreased expression of beta-tubulin, actin, JCW1, HRGP and GRP and increased expression of sbPRP1, pGE95 and pGE16 in the hypocotyl zone of cell elongation could participate in the reversible growth inhibition observed in water-deficient soybean seedlings. PMID- 1912488 TI - Isolation and characterization of a cDNA clone encoding the anti-viral protein from Phytolacca americana. AB - Phytolacca anti-viral protein (PAP) was purified from Phytolacca leaves and the N terminal was sequenced. A cDNA library was made from mRNAs isolated from Phytolacca leaves and cDNA clones for PAP were identified using oligonucleotide probes derived from the N-terminal amino acid sequence. The PAP-cDNA clone was sequenced from both directions. The predicted amino acid sequence of PAP was compared with the amino acid sequences of other ribosome-inactivating proteins. The identities of these proteins to PAP ranged from 29 to 38%, and a region was found in each with a sequence similar to the PAP sequence (AIQMVSEAARFKYI). Southern blot analysis indicates that PAP is encoded by a multi-gene family. PMID- 1912489 TI - Populus chitinase genes: structure, organization, and similarity of translated sequences to herbaceous plant chitinases. AB - Poplar trees have at least two different chitinase genes, win6 and win8, which are systemically wound-inducible and belong to multigene families [Proc Natl Acad Sci USA 86: 7895-7899]. On one genomic clone that we have partially sequenced, there are three win6 genes which are transcriptionally oriented in the same direction. Between two of the win6 genes is a gene that we have designated chitinase X (chiX), which appears to be a pseudogene belonging to a multigene family distinct from win6 and win8. The win6 and chiX genes we have sequenced contain two AT-rich introns that correspond in location to those in a basic chitinase gene from tobacco. The predicted Win6 proteins have a putative signal peptide, a cysteine-rich 'hevein' domain, a hinge region, and a catalytic domain as described in Shinshi et al. [Plant Mol Biol 14: 357-368]. The predicted Win8 protein, by contrast, completely lacks a hinge region. Both Win6 and Win8 are expected to be highly acidic (with a calculated net charge of -15 to -17), whereas ChiX proteins are likely to be basic. Based on an inferred phylogeny, the catalytic domain of ChiX is more closely related to the basic chitinases of herbaceous plants than are either Win6 or Win8. PMID- 1912490 TI - Stress responses in alfalfa (Medicago sativa L.) 11. Molecular cloning and expression of alfalfa isoflavone reductase, a key enzyme of isoflavonoid phytoalexin biosynthesis. AB - The major phytoalexin in alfalfa is the isoflavonoid (-)-medicarpin (or 6aR, 11aR)-medicarpin. Isoflavone reductase (IFR), the penultimate enzyme in medicarpin biosynthesis, is responsible for introducing one of two chiral centers in (-)-medicarpin. We have isolated a 1.18 kb alfalfa cDNA (pIFRalf1) which, when expressed in Escherichia coli, converts 2'-hydroxyformononetin stereospecifically to (3R)-vestitone, as would be predicted for IFR from alfalfa. The calculated molecular weight of the polypeptide (35,400) derived from the 954 bp open reading frame compares favorably to estimated Mrs determined for IFR proteins purified from other legumes. The transcript (1.4 kb) is highly induced in elicited alfalfa cell cultures. The kinetics of induction are consistent with the appearance of IFR activity, the accumulation of medicarpin, and the observed induction of other enzymes in the pathway. Low levels of IFR transcripts were found in healthy plant parts (roots and nodules) which accumulate low levels of a medicarpin glucoside. IFR appears to be encoded by a single gene in alfalfa. The cloning of IFR opens up the possibility of genetic manipulation of phytoalexin biosynthesis in alfalfa by altering isoflavonoid stereochemistry. PMID- 1912491 TI - Seasonal changes in the concentration of the major storage protein and its mRNA in xylem ray cells of poplar trees. AB - In the autumn large amounts of a major storage protein accumulate in the woody stem of poplar trees. This protein is stored in xylem ray cells during the winter season and is degraded in late spring. The accumulation of this protein is preceded by a dramatic but transient appearance of the corresponding mRNA. Thus, the seasonal change in the mRNA content appears to be a crucial event for the storage of nitrogen in the stem. The amino acid sequence of the storage protein has been deduced from the nucleotide sequence of a full-length cDNA. The cDNA shows a nucleotide sequence similarity of approximately 75% with two published cDNA sequences of poplar which represent transcripts that accumulate systemically in leaves of poplar trees in response to wounding. PMID- 1912492 TI - Isolation and characterization of cDNA clones for RNA species induced by substituted benzenesulfonamides in corn. AB - A search of compounds capable of inducing specific gene expression in plants without affecting growth and development led to the examination of changes in the pattern of gene expression in corn after treatment with substituted benzenesulfonamide herbicide safeners. Following hydroponic treatment of corn with the safener N-(aminocarbonyl)-2-chlorobenzenesulfonamide (2-CBSU), the specific induction of new translatable mRNA species was observed. Replicate copies of a cDNA library made using RNA from 2-CBSU-treated corn roots were differentially screened with cDNA probes made from either the same mRNA fraction used for library construction or mRNA isolated from roots treated with 2 chlorobenzenesulfonamide (2-CBSA), an inactive analog of the safener. Colonies showing hybridization only with the probe made using mRNA from 2-CBSU-treated roots were further characterized to assess the specificity of the induction and decay of the corresponding induced RNA species. RNA blot analyses showed two clones, designated In2-1 and In2-2, contained plasmids that hybridized to RNAs that were induced from an undetectable background in corn roots within 30 minutes after treatment with 2-CBSU. Leaf and meristem tissues showed similar inductions of the In2-1 and In2-2 RNA species after a delay of several hours. In addition, both RNA species were induced in corn by foliar application of 2-CBSU. In contrast, neither RNA species was induced following stress treatments of plants. These results indicate a substituted benzenesulfonamide safener might be used with the promoters from the In2-1 and In2-2 genes to develop a new inducible gene expression system for plants. PMID- 1912493 TI - Expression of a chimaeric granule-bound starch synthase-GUS gene in transgenic potato plants. AB - Granule-bound starch synthase is the key enzyme in amylose synthesis. The regulation of this gene was investigated using a chimaeric gene consisting of a 0.8 kb 5' upstream sequence of the granule-bound starch synthase gene from potato and the beta-glucuronidase gene which was introduced into potato using an Agrobacterium tumefaciens binary vector system. The chimaeric gene was highly expressed in stolons and tubers, whereas the expression in leaves, stems or roots from greenhouse-grown plants was relatively low. However, leaves from in vitro grown plantlets exhibited an elevated GUS expression. The expression of the chimaeric gene was inducible in leaves by growth on relatively high concentrations of sucrose, fructose and glucose and was about 30- to 50-fold higher than in leaves from greenhouse-grown plants. The granule-bound starch synthase gene is expressed organ-specifically since stolons and tubers showed GUS activities 125- to 3350-fold higher than in leaves. The activities in these two organs are 3- to 25-fold higher than the expression of the CaMV-GUS gene. Histochemical analysis of different tissues showed that only certain regions of leaves and roots express high GUS activities. Stolons and tubers show high expression. PMID- 1912494 TI - Expression of a Brassica napus extensin gene in the vascular system of transgenic tobacco and rape plants. AB - The organs and tissues where the Brassica napus extA extensin gene is expressed have been identified. The extA gene with 3.75 kb of 5' flanking sequence was transferred to tobacco via disarmed Agrobacterium tumefaciens vectors and transgenic plants regenerated. The gene was found to be inactive in transgenic tobacco leaf, but was active as measured by RNA transcript assays in both stem and root tissues. To determine the cell-specific expression pattern of the extA gene, a promoter-reporter gene fusion construct was made consisting of 1.0 kb of 5' extA sequence fused to the coding region of the glucuronidase (GUS) gene. This fusion construct was introduced into B. napus via Agrobacterium rhizogenes, and expression of GUS in transgenic rape hairy roots was examined. GUS activity was only seen in the vascular tissues of the rape root, and was found to be specifically localised in the phloem. PMID- 1912495 TI - Regulation of Agrobacterium tumefaciens T-cyt gene expression in leaves of transgenic potato (Solanum tuberosum L. cv. Desiree) is strongly influenced by plant culture conditions. AB - The promoter region of the Agrobacterium tumefaciens T-cyt gene was linked in a translational fusion to the coding DNA of the reporter gene uidA (for beta glucuronidase or GUS protein; EC 3.2.1.31) and to nos 3' flanking DNA. The chimaeric gene was introduced by Agrobacterium transformation into potato (Solanum tuberosum L. cv. Desiree). In nine transgenic lines, the average GUS levels were highest in extracts from stems and roots of in vitro grown plants (ca. 11,000 GUS activity units per pmol MU per mg protein per min) but lower in leaves of the in vitro grown plants (ca. 7000 units). GUS activity was intermediate in stems and roots of plants grown in soil as well as in in vitro crown galls (ca. 3000 units). Activity was low in tubers, irrespective of whether these developed in vitro or in soil (both ca. 100 units), and lowest of all in leaves of soil-grown plants (ca. 10-15 units). However, in shoot cultures reestablished from soil-grown plants, GUS activity in the leaves increased to that determined in the original shoot cultures. Hence, plant culture conditions strongly influenced the expression of the T-cyt-uidA-nos gene. In particular, it was silenced in leaves of soil-grown plants. The results are compared with previous analyses of the promoter region of the wild-type T-cyt gene and with the growth properties of a large number of crown gall cell lines and crown-gall derived plants, including over forty S. tuberosum cv. Desiree cell lines isolated in the present study that were transformed with the wild-type T-cyt gene and six promoter-mutated derivatives. A number of implications are discussed for crown gall formation and for control of expression of plant genes which contain Activator or G-box type 5' expression control sequences. PMID- 1912496 TI - Phenotypic changes in T-cyt-transformed potato plants are consistent with enhanced sensitivity of specific cell types to normal regulation by root-derived cytokinin. AB - From over forty independently isolated potato lines transformed with wild-type and promoter-mutated T-cyt genes, a number of lines were selected for examination of phenotypic changes in growth and development for plants grown in soil in a controlled environment. The three lines chosen for most detailed examination showed a wide spectrum of phenotypic changes. In comparisons with control potato cv. Desiree, the plants of one line had a two- to three-fold increase in biomass production during early vegetative growth, advanced senescence and a shortened plant life-span. Another line showed abnormal cellulytic senescence. In two lines there were increases in tuber numbers and more skewed tuber size distributions which correlated with reduced shoot apical dominance and shortened dormancy of the stored tubers. None of the lines showed altered timing of onset of tuberization or flowering, although tuberization was consistently delayed when expressed as a function of increasing total plant weight. A hypothesis is proposed to explain the diverse phenotypes which postulates that (1) T-cyt transformation causes enhanced sensitivity to cytokinins in specific types of shoot cells which are already targets for regulation by normal root-derived cytokinins; (2) two distinct types of shoot target cells are present, one in shoot meristems and one in leaves; (3) the two types can acquire enhanced sensitivity, either separately or in combination depending on the particular T cyt transformation event. The scope for using the transformed plants in subsequent physiological, biochemical and molecular studies, aimed at examining the molecular basis of the model or selected consequences of T-cyt transformation in altering regulation of potato plant growth and development, is discussed. The attention is drawn to the possible involvement at the subcellular level of sucrose phosphate synthase in mediating the phenotypic effects caused by T-cyt transformation. PMID- 1912497 TI - The tomato Cu,Zn superoxide dismutase genes are developmentally regulated and respond to light and stress. AB - The expression of the two Cu,Zn superoxide dismutase (SOD) genes of tomato was followed in different organs and plant developmental stages at the transcript and enzymatic activity levels. The cDNA clones used as probes code for the chloroplast Cu,Zn SOD (clone T1) and the cytosolic Cu,Zn SOD (clone P31). The two genes were found to display distinct expression patterns. While the T1 transcript was rare or absent from roots, stems and ripening fruits, the P31 transcript was very abundant in these organs. Shoot tips, flower buds, seedlings and young leaves contained high levels of the two mRNAs. During leaf expansion, the levels of both transcripts diminish markedly. Despite the diminished presence of transcripts, SOD activity levels of the corresponding cytosolic and chloroplast isozymes accumulated and were sustained throughout leaf expansion. In non photosynthetic organs, the SOD-3 (cytosolic) isozyme contained most of the activity, while in the expanded leaf the SOD-1 (chloroplast) isozyme was more abundant. Light-regulated accumulation of both the P31 transcript (1.7-fold) and the T1 transcript (3-fold) was observed upon light exposure of etiolated seedlings. However, only SOD-1 activity was observed to increase, after a lag of a few hours. The levels of both transcripts increased in response to paraquat and mechanical wounding. The level of the cytosolic transcript and the respective isozyme activity increased dramatically during prolonged drought stress while the chloroplast transcript remained unaffected. The expression of both genes was enhanced by spraying tomato plants with ethephon--a compound that releases ethylene. Our data show that the expression of Cu,Zn SOD genes in tomato is modulated in response to a variety of factors and suggest the importance of oxyradical toxicity as well as the role of SOD in the defence mechanism of plants exposed to stress. PMID- 1912498 TI - Substances in nuclear wheat germ extracts which interfere with polymerase III transcriptional activity in vitro. AB - Wheat germ nuclear extracts inhibited an active yeast polymerase III (pol III) transcription extract. We isolated two chromatin-associated fractions which harbored biochemically distinguishable inhibitory activities, each contributing about 40-50% to the total inhibitory activity. One fraction, which was released from the chromatin upon treatment with 350 to 900 mM NaCl, was purified to homogeneity and identified as histone H1. It inhibited the yeast extract by excluding the transcription machinery from the template DNA. It can be partially antagonized by additional nontemplate DNA together with templates that have strong pol III promoters. The other fraction, which was released from the chromatin between 0 and 350 mM NaCl, inhibited transcription by affecting transcription complex formation partially through transcription factor-inhibitor interactions. Furthermore, it affected the rate of transcription reinitiation but not the elongation rate. Ways to move towards an active DNA-dependent pol III plant extract are discussed. PMID- 1912499 TI - Homologues of the green algal gidA gene and the liverwort frxC gene are present on the chloroplast genomes of conifers. AB - Strong hybridization signals were obtained from total DNA of two conifers, lodgepole pine (Pinus contorta) and Norway spruce (Picea abies), in a Southern blot analysis using a probe derived from the chloroplast gidA gene of the green alga Chlamydomonas reinhardtii. The pine fragments detected by the probe were found to originate from the chloroplast genome and, as judged by the signal intensity, this was also true for the spruce fragments. Sequence analysis of the hybridizing pine chloroplast DNA region revealed an open reading frame potentially encoding a 459 amino acid polypeptide, highly homologous to that deduced from the algal gene and to ORF465 of liverwort chloroplast DNA. Upstream of the gidA sequence, we found a trnN(GUU) gene and an open reading frame of 291 codons which was 78% identical to the frxC gene of liverwort. Since ORF465 is located immediately downstream of trnN and frxC in liverwort, the genetic organization of this region is very similar in the two plants. In contrast, neither the gidA nor the frxC gene is present in the chloroplast DNA of tobacco or rice. It was recently reported that deletions in the gidA region of the chloroplast genome of Chlamydomonas reinhardtii abolish the light-independent pathway of chlorophyll synthesis which exists in many algae and lower plants. The presence of the gidA gene on the chloroplast genomes of conifers may therefore be of significance with respect to the ability of these plants to synthesize chlorophyll in the dark. PMID- 1912500 TI - Chloroplast transcription is required to express the nuclear genes rbcS and cab. Plastid DNA copy number is regulated independently. AB - RbcL and rbcS mRNA levels and plastid transcription activity are low in the basal meristematic region of barley primary leaves and increase coordinately during leaf cell development with a similar time course in dark-grown or illuminated seedlings. The capacity of light to cause cab mRNA accumulation shows a similar dependence on leaf cell development. These results indicate that the initial activation of chloroplast gene expression and the expression of some nuclear genes encoding plastid proteins are coupled to leaf cell development. RbcL and rbcS mRNA levels and plastid transcription activity decline in older leaf sections of dark-grown or illuminated barley. The decreases in plastid transcription and rbcS and rbcL mRNA levels in older dark-grown seedlings could be reversed by plant illumination. Therefore, while the initial activation of plastid transcription and accumulation of rbcS mRNA are largely light independent, these events become light-dependent in older leaves of dark-grown barley. If the initial increase in plastid transcription which occurs early in leaf cell development is prevented by tagetitoxin, a specific inhibitor of the plastid RNA polymerase, rbcS mRNA does not accumulate and cab mRNA accumulation cannot be induced by light. The effect of tagetitoxin is selective because this compound does not inhibit barley leaf growth, or the normal accumulation of nuclear-encoded actin and BN3 transcripts and plastid DNA which occurs during chloroplast development. Furthermore, a barley pigment-deficient mutant, alb-f17, and plants containing photo-oxidized plastids show parallel reductions in plastid transcription activity and levels of rbcS and cab mRNA. This suggests that the activation of plastid transcription during the early stages of chloroplast biogenesis is necessary for the expression of rbcS and cab. PMID- 1912501 TI - Phenotypically normal transgenic T-cyt tobacco plants as a model for the investigation of plant gene expression in response to phytohormonal stress. AB - The tumour-inducing T-DNA gene 4 (T-cyt gene) of the nopaline Ti plasmid pTiC58 was cloned and introduced into tobacco cells by leaf disc transformation using Agrobacterium plasmid vectors. Tobacco shoots exposed to elevated cytokinin levels were unable to develop roots and lacked apical dominance. Using exogenously applied phytohormone manipulations we were able to regenerate morphologically normal transgenic tobacco plants which differed in endogenous cytokinin levels from normal untransformed plants. Although T-cyt gene mRNA levels, as revealed by dot-blot hybridization data, in these rooting plants were only about half those in primary transformed shoots the total amount of cytokinins was much lower than in crown gall tissue or cytokinin-type transformed shoots as reported by others. Nevertheless the cytokinin content in T-cyt plants was about 3 times greater than in control tobacco plants. Elevated cytokinin levels have been shown to change the expression of several plant genes, including some nuclear genes encoding chloroplast proteins. Our results show that the mRNA levels of chloroplast rbcL gene increase in cytokinin-type transgenic tobacco plants as compared with untransformed plants. Data obtained suggest that T-cyt transgenic plants are a good model for studying plant gene activity in different parts of the plant under endogenous cytokinin stress. PMID- 1912502 TI - Mismatch-specific DNA breakdown in nuclear extract from tobacco (Nicotiana tabacum) callus. AB - Mismatch-specific enzymatic activity was sought for in nuclei from normal and transformed plant cells originating from tobacco (Nicotiana tabacum) callus and crown gall tumor induced by Agrobacterium tumefaciens. The specific enzymatic activity was assayed with substrates derived from synthetic oligonucleotides (19 mer sequences corresponding to the human K-ras gene). Single-base changes in the middle of the sequence were the basis for creating heteroduplexes with all eight mismatches. Homo- and heteroduplexes were ligated in a size ladder and used as substrates. We detected mismatch-specific DNA breakdown and determined basic requirements for the reactions. Kinetic analysis indicates the following reactivity order of preference: C:A=C:C=C:T greater than G:T approximately A:A approximately G:A approximately G:G approximately T:T much greater than G:C. It can be said now that specific mismatch recognition and repair activities have been detected in all kingdoms of living species. PMID- 1912503 TI - cDNA cloning and expression of Brassica napus enoyl-acyl carrier protein reductase in Escherichia coli. AB - The onset of storage lipid biosynthesis during seed development in the oilseed crop Brassica napus (rape seed) coincides with a drastic qualitative and quantitative change in fatty acid composition. During this phase of storage lipid biosynthesis, the enzyme activities of the individual components of the fatty acid synthase system increase rapidly. We describe a rapid and simple purification procedure for the plastid-localized NADH-dependent enoyl-acyl carrier protein reductase from developing B. napus seed, based on its affinity towards the acyl carrier protein (ACP). The purified protein was N-terminally sequenced and used to raise a potent antibody preparation. Immuno-screening of a seed-specific lambda gt11 cDNA expression library resulted in the isolation of enoyl-ACP reductase cDNA clones. DNA sequence analysis of an apparently full length cDNA clone revealed that the enoyl-ACP reductase mRNA is translated into a precursor protein with a putative 73 amino acid leader sequence which is removed during the translocation of the protein through the plastid membrane. Expression studies in Escherichia coli demonstrated that the full-length cDNA clone encodes the authentic B. napus NADH-dependent enoyl-ACP reductase. Characterization of the enoyl-ACP reductase genes by Southern blotting shows that the allo-tetraploid B. napus contains two pairs of related enoyl-ACP reductase genes derived from the two distinct genes found in both its ancestors, Brassica oleracea and B. campestris. Northern blot analysis of enoyl-ACP reductase mRNA steady-state levels during seed development suggests that the increase in enzyme activity during the phase of storage lipid accumulation is regulated at the level of gene expression. PMID- 1912504 TI - Amino acid sequence analysis of rape seed (Brassica napus) NADH-enoyl ACP reductase. PMID- 1912505 TI - Nucleotide sequence of the Spirodela oligorrhiza chloroplast psbA gene coding for the D1 (32 kDa) photosystem II protein. PMID- 1912506 TI - Sequence of a tomato gene encoding a third type of LHCII chlorophyll a/b-binding polypeptide. PMID- 1912507 TI - Isolation and sequence determination of the plant homologue of the eukaryotic initiation factor 4D cDNA from alfalfa, Medicago sativa. PMID- 1912508 TI - Cloning and sequence analysis of the phycocyanin genes of the marine cyanobacterium Synechococcus sp. WH7803. PMID- 1912509 TI - Organ-specific expression of different histone H3 and H4 gene subfamilies in developing and adult maize. AB - The steady-state levels of H3 and H4 mRNAs transcribed from three H3 and two H4 multigene subfamilies were studied during germination and in different organs of maize. During germination the five subfamilies are expressed in parallel to DNA synthesis, but a 5-fold difference in the quantity of mRNAs transcribed per gene copy was found from our subfamily to another. In adult plants H3 and H4 mRNA levels are highest in organs containing meristematic tissues but also high in non proliferating tissues. No strict tissue specificity expression could be detected but some subfamilies show preferential expression in some tissues. PMID- 1912510 TI - Characterization of genes encoding hydroxypyruvate reductase in cucumber. AB - Several clones corresponding to the gene encoding NADH-dependent hydroxypyruvate reductase have been isolated from a cucumber genomic library. Restriction mapping indicates the presence of two HPR genes, hpr-A and hpr-B, in the cucumber genome. Examination of the DNAs of individual plants suggests that hpr-A and hpr-B are most likely alleles at a single locus. The sequence of a 6.7 kb genomic fragment that includes the entire transcribed region, 2.2 kb of 5' flanking sequence, and about 0.8 kb of 3' flanking sequence reveals the presence of 12 introns in hpr-A. These introns are AT-rich relative to the exons. The donor sequence at the 5' end of the sixth intron contains an unusual dinucleotide, GC, rather than the nearly invariant GT. Primer extension analysis maps the transcription initiation site to 61 nucleotides upstream of the translation initiation codon. An AT-rich stretch is centered at position -31 with respect to the transcription initiation site, and a potential CCAAT box is centered at position -138. Several elements that are homologous to regulatory elements of other plant genes have been identified in the flanking regions of hpr-A. PMID- 1912511 TI - Nucleotide sequence and expression of a novel glycine-rich protein gene from Arabidopsis thaliana. AB - A clone containing a gene coding for a novel glycine-rich protein has been identified in an Arabidopsis thaliana genomic library. The gene codes for a 339 amino acid protein and is interrupted by a 686 bp intervening sequence. The gene is present in one copy only. Transcripts accumulate mainly in hypocotyls and stems and the highest level is observed in rosettes before the start of stem elongation. The protein contains 71% of glycine residues and is highly hydrophobic. PMID- 1912512 TI - Nucleotide sequence of a cDNA clone encoding a putative glycine-rich protein of 19.7 kDa in Nicotiana sylvestris. PMID- 1912513 TI - The role of MHC class I expression in developmental tumours. AB - Expression of HLA class I (-like) genes by two developmental tumour cell lines representing embryonic (Tera-2) and extra-embryonic (Jeg-3) origins is reviewed. The Tera-2 embryonal carcinoma cells are HLA negative but can be induced by gamma interferon to express HLA-A, -B, -C, and apparently -E and G genes. Jeg-3 choriocarcinoma cells constitutively express HLA-G and low levels of a novel HLA C gene product. The NK sensitivity of the developmental tumour cell types has been assessed and the biochemical characteristics of the surface molecules expressed by the trophoblast derived cells has been further documented. The biological role of these novel HLA molecules in the context of the maternal acceptance of the fetal-semi-allograft is discussed. PMID- 1912514 TI - MHC antigen expression in colorectal tumours. AB - This article reviews abnormalities in the expression of major histocompatibility antigens in colorectal neoplasia. These include the loss of HLA-A, B, C antigens and the loss of HLA-D antigen inducibility. Since these abnormalities are not seen in normal colorectal epithelium they are probably selected for during tumour progression. The crucial role of HLA-A, B, C and HLA-D molecules in the presentation of foreign antigens to the immune system suggests that their loss could directly confer a selective growth advantage to tumour cells expressing tumour specific antigens, through resistance to anti-tumour lymphocyte attack. The possible relationships between abnormalities in tumour HLA antigen expression and the presence of tumour specific antigens are discussed. PMID- 1912515 TI - Regulation of HLA class I gene expression in human colorectal carcinoma. AB - The under-representation of HLA antigens in human tumors is usually associated with a poor prognosis. In this report, the expression of HLA class I genes in human colorectal carcinomas was studied using HLA-A and HLA-B locus-specific probes. Over 50% of the colorectal carcinomas studied showed a reduction in the amount of steady state HLA class I mRNA. For some carcinomas, non-coordinated regulation of the HLA-A and HLA-B genes was observed. The mechanism of HLA suppression was investigated and is most likely due to the presence of transcriptional regulatory elements. PMID- 1912516 TI - MHC expression on human tumors--its relevance for local tumor growth and metastasis. AB - MHC class I and II molecules play an important role in specific interactions with cells of the immune system. Endogenous or exogenous antigens are presented to the clonotypic receptor of T cells as small peptides associated to MHC molecules. Qualitative or quantitative variation in the expression of these molecules in the surface of tumor cells could have important implications in anti-tumor immune responses. We have analysed 344 human tumors for HLA class I and II expression and found that 10-30% of tumors present a total loss of HLA ABC molecules. In addition, HLA-A or -B locus-specific losses were also detected. These alterations have been correlated with tumor aggressiveness in breast and laryngeal carcinomas. We also have observed that the expression of HLA ABC molecules in autologous metastasis did not always correspond with the expression detected in the primary tumor. In laryngeal carcinomas HLA-DR expression was associated with an excellent prognosis. We have observed in most tumors that the absence of class I molecules usually corresponds with a simultaneous loss of heavy chain and beta 2 microglobulin expression and with a low level of the mRNA specific for class I genes. Nevertheless, a variety of mechanisms are involved since in colon tumors the absence of expression is caused by beta 2 microglobulin down regulation. Also post-transcriptional mechanisms may be involved in the differential expression of HLA-A and -B locus products. There is no doubt that a more exact knowledge of the mechanisms that produce alteration in the expression of these antigens will help to manipulate MHC gene expression in human tumors and to induce a more efficient immune response. PMID- 1912517 TI - MHC antigens in human melanomas. AB - The distribution of MHC antigens in human melanocytic lesions, i.e. HLA class I and HLA class II antigens is reviewed. HLA class I antigens have a broad distribution, but may be lost during tumor progression. In contrast, HLA class II antigen expression appears with neoplastic transformation. The mode of regulation of HLA antigens in melanoma lesions is complex. Immunohistochemical demonstration of HLA antigen expression in primary melanoma lesions and in locoregional metastases has prognostic relevance. Expression of HLA-DR in primary melanoma lesions is associated with an unfavorable prognosis, as is a decreased expression of HLA-A,B,C antigens in locoregional metastases. PMID- 1912518 TI - Tumor aggressiveness and MHC class I and II antigens in laryngeal and breast cancer. AB - HLA class I and II molecules play an important role in the immune system. Thus, alterations in their expression could affect the immunosurveillance against tumors. The expression of these molecules may therefore be one of the factors responsible for oncogenicity, due to their role as restriction elements in T cell recognition. A series of 78 primary laryngeal and 94 breast tumors were evaluated for the expression of MHC class I and II antigens, using monoclonal antibodies. We found a number of cases presenting total loss of HLA-ABC and selective losses of HLA-A and HLA-B antigens. These losses were statistically associated with clinical and pathological parameters such as T stage, degree of differentiation, scores according to the malignancy grading systems and degree of leukocytic infiltration. On the other hand, the de novo expression of DR antigens in laryngeal cancer was found in a group of neoplasms having a peculiar clinical behavior and excellent prognosis. Expression of class II molecules in breast tumors was also related to a better differentiation and prognosis. Thus, HLA class I and II antigen expression is closely related to aggressiveness and prognosis of laryngeal and breast cancer. PMID- 1912519 TI - Sensitivity of melanoma cell lines to natural killer cells: a role for oncogene modulated HLA class I expression? AB - N-ras and c-myc oncogenes were found to be activated in melanoma. High c-myc expression renders melanoma cell lines sensitive to lysis by natural killer (NK) cells. This effect is mediated by locus-specific downmodulation of HLA-B expression by c-myc. Cell lines with a mutation in the N-ras gene were relatively sensitive to NK cells irrespective of HLA class I expression. These findings indicate that NK cells can kill tumor cells with activated myc or ras oncogenes in various ways, thus providing potential mechanisms to eliminate cancer cells with an activation of these oncogenes. PMID- 1912520 TI - Genetic control of the metastatic phenotype. AB - Transfection experiments indicate that a number of genes can induce or suppress the metastatic phenotype. These genes include ten oncogenes, plasminogen activator, and three suppressor genes. The biochemical mechanism(s) whereby each of these genes alters the metastatic phenotype is poorly understood. Hypotheses concerning the coordinate regulation of metastasis-effector genes, and the relationship of gene expression in metastasis to that in embryonic development are discussed. PMID- 1912521 TI - Tumor cell motility. AB - Tumor cell motility is required for invasion and metastasis. The locomotory machinery of the cell includes cell projections called pseudopodia which are regulated by a complicated linkage between cell surface receptors or sensors and the internal cytoskeleton. Recently a new class of motility stimulating cytokines have been identified. These cytokines can function as autocrine motility factors and require a pertussis toxin sensitive G protein pathway to transduce a random motile response. PMID- 1912522 TI - Tumor cell progression and differentiation in metastasis. AB - The development and evolution of tumors is regulated by both genetic and epigenetic events. It is thought that these processes tend to drive neoplastic development in opposing directions so that tumor progression, predominantly as a consequence of mutational events, leads to increasing tumor aggression. Conversely the induction of differentiation, largely through epigenetic mechanisms, tends to cause tumors to evolve to a more benign phenotype. However, these generalizations are a simplistic view of a complex dynamic event where both processes can be overlaid within a single neoplasm. Using malignant melanoma as a model system the alterations in gene expression and their effects upon metastatic dissemination, that accompany some of these changes, both natural and induced, are described. PMID- 1912523 TI - Cell-to-cell interaction in regulating diversity of neoplasms. AB - Cancers contain a diverse array of clonal subpopulations that reflect an underlying instability in the cancer cell genome. Over time new clones arise and new proportional balances are reached among the existing clones. Both phenomena are regulated, in part, by cellular networks that include normal-to-cancer and cancer-to-cancer cell interactions. The mechanisms of these interactions vary with the circumstances and with the interacting cells. They include contact mediated events, growth and other factors, and host-determined reactions. The over-all result is a cancer cell society in which the behavior of the component parts is modified by the exigencies of tissue life. PMID- 1912524 TI - Tumor and host molecules important in the organ preference of metastasis. AB - Many cancers metastasize nonrandomly to particular distant sites, and their colonization properties cannot be explained by mechanical considerations, such as arrest of tumor cells in the first microcirculatory network encountered. Metastatic cells that show a high propensity to metastasize to certain organs adhere at higher rates to microvessel endothelial cells isolated from these target sites, invade into target tissue at higher rates and respond better to paracrine growth factors from the target site. These properties depend on multiple tumor cell, host cell, and stromal molecules that are differentially expressed by particular tumor and organ cells and by the extracellular matrix. For example, some of the adhesion molecules involved in tumor cell-endothelial cell adhesion have been identified on both tumor and host cells. Among them are: integrins, endogenous lectins, annexins, and other molecules. The invasive properties of particular tumor cells are dependent on the production of degradative enzymes, such as metalloproteinases, heparanase and cys and ser proteinases, and on responses to organ-derived paracrine and autocrine motility factors. The subsequent growth of particular tumor cells at certain organ sites is determined, in part, by their responses to organ paracrine growth factors and the organ extracellular matrix. Collectively these factors appear to determine the organ colonization properties of blood-borne metastatic cells. PMID- 1912525 TI - Tumor cell adhesive mechanisms and their relationship to metastasis. AB - Despite recent advances in the diagnosis and therapy of many forms of cancer, metastasis remains the major cause of death in cancer patients. As tumors progress they become increasingly heterogeneous, giving rise to aggressive subpopulations of tumor cells that subsequently invade local tissues, the lymphatics, and the circulatory system. This invasive behavior can ultimately lead to the widespread dissemination and metastasis of the primary tumor. In hematogenous metastasis, emboli consisting of tumor cells, host cells, platelets, and fibrin are transported to distant sites where they arrest in the microvasculature prior to extravasation. It is well accepted that tumor cell adhesion plays a fundamental role in many of the stages of the metastatic process. Tumor cell interactions with extracellular matrix components of tissue, tissue boundaries (basement membranes), or cell adhesion-promoting components of plasma; influence tumor cell motility, invasiveness, and many other important aspects of the metastatic tumor cell phenotype. Tumor cell adhesion also has a rate-limiting influence at various stages within the metastatic process, such as tumor cell arrest and extravasation. In addition, the ability of the immune system to recognize and successfully eradicated tumors is also highly dependent on the adhesion of activated lymphocytes to target tumor cells. Despite the rapid accumulation of information on the molecular basis of cell adhesion, our understanding of the relationship between tumor cell adhesion and hematogenous metastasis per se is fragmented and incomplete. Nevertheless, clear progress has been made, both in understanding the molecular basis of tumor cell adhesion and its relationship to the biology of tumor metastasis. New and exciting directions have been identified that are likely to yield direct benefits in developing new therapeutic or diagnostic approaches for malignant neoplasms. Our purpose is to briefly review the molecular basis of tumor cell adhesion from the standpoint of many of the receptors involved as well as their putative ligands. The relationship between specific tumor cell adhesion events and the formation of metastatic lesions is also addressed. PMID- 1912526 TI - Tumor cell surface determinants in host immunity against metastases. AB - The treatment of cancer through the action of natural host defense mechanisms has been the goal of basic research and medicine. Expanding our understanding of the structure and function of major histocompatibility antigens (MHC) and of their interaction with peptide antigens in T cell immunity, and integrating it with the emerging data on the nature of tumor rejection antigens, may advance our ability to manipulate the immunogenicity of tumors. Downregulation of MHC class I in murine tumors and human tumors and the manipulation of some experimental systems is described. PMID- 1912527 TI - Molecular mechanisms for activated macrophage recognition of tumor cells. AB - The biological heterogeneity of tumor cells requires a therapeutic modality that recognizes and kills resistant as well as susceptible tumor cells but does not harm normal cells. Tumoricidal macrophages appear to be able to fulfill these criteria. The mechanisms by which macrophages recognize tumor cells are not known, but they recognize carbohydrates and proteins that may be relevant for binding to tumor cells. In addition, phospholipids appear to be involved in the macrophage-tumor cell interaction. The abnormal presence of phosphatidylserine (PS) on the outer leaflet of tumor cells correlates with enhanced binding and cytotoxicity by macrophages. PMID- 1912528 TI - Retinoids as modulators of tumor cells invasion and metastasis. AB - Retinoids, natural and synthetic analogues of vitamin A, have demonstrated promising results in pre-clinical and clinical trials of cancer prevention and therapy. This chapter reviews the ability of retinoids to suppress tumor growth and metastasis in vivo and to inhibit invasion in vitro. The mechanisms of these effects include suppression of growth and enhancement of differentiation of malignant cells, inhibition of their ability to produce degradative enzymes required for invasion, suppression of migration, inhibition of neovascularization, and augmentation of host anti-tumor immune responses. PMID- 1912529 TI - Acquired versus intrinsic resistance to methotrexate: diversity of the drug resistant phenotype in mammalian cells. AB - The expression of resistance by tumor cells to anticancer drugs remains a primary cause of patient failure to chemotherapeutic intervention in cancer. Although studied for many years, both the acquisition and maintenance of drug resistance continue to provide active areas for research and the application of modern molecular and cell biological techniques to those questions has begun to generate a wealth of new information. This article attempts to summarize and contrast some of the more recent observations concerning acquired and intrinsic resistance to the classical antifolate methotrexate, and suggests that the mechanisms of intrinsic resistance, and to a lesser extent acquired resistance as well, may be more broad based than previously thought and that the expression of intrinsic resistance may be strongly influenced by physiological and genetic variation. PMID- 1912530 TI - Metallothionein expression and transient resistance to electrophilic antineoplastic drugs. AB - Intrinsic and acquired resistance to antineoplastic agents remains an important impediment to cancer therapy. Intracellular metallothioneins appear to be one factor in determining the responsiveness of malignant and normal cells to electrophilic anticancer agents. Metallothioneins are not only constitutively expressed but their expression can be transcriptionally activated by a host of endogenous and exogenous substances; this is a reversible phenomenon. This inducibility affords the possibility that cells can respond quickly to toxic substances and that under certain conditions transient drug resistance may occur. We review the evidence implicating metallothioneins in anticancer drug resistance and discuss this in the context of the possibility of transient resistance. PMID- 1912531 TI - Wasting and malnutrition in patients with HIV/AIDS. AB - It is important for healthcare professionals caring for HIV-infected individuals to understand the relationship among nutrition, HIV infection, and the immune system. Progressive weight loss is a major component of the clinical syndrome in persons with HIV infection and AIDS. Weight loss occurs for a variety of reasons, which, when recognized, may be preventable or treatable. Malnutrition occurring with weight loss may adversely affect the function of the immune system and further impair the infected individual's ability to avoid or recover from infection. Nursing interventions in nutritional care, outlined in this article, can help these clients improve both the quantity and quality of their lives. PMID- 1912532 TI - Patient satisfaction on AIDS and oncology special care units and integrated units: a pilot study. AB - The authors assessed patients' satisfaction with their nursing care in seven hospitals. Five of the hospitals utilized the special care unit (SCU) method of delivering care to AIDS or oncology patients; three had SCUs for AIDS patients. All seven of the hospitals had integrated units (IUs) where general medical, oncology, and/or AIDS patients were received in various proportions. Satisfaction with nursing care was measured with the Risser Patient Satisfaction Instrument. Patient satisfaction with nursing care was shown to be a function of delivery method; AIDS and oncology patients on SCUs expressed greater satisfaction with their care than medical, oncology, or AIDS patients on IUs (p less than .001). Patient satisfaction with nursing care was greater among whites than nonwhites. Also, some major sociodemographic and case mix variables, such as age, employment status, and diagnosis, were not associated with patient satisfaction directly; in other instances, the associations initially seen did not hold when delivery method (SCU vs. IU) and race were controlled for in a linear regression analysis. PMID- 1912533 TI - Heroic measures for patients with AIDS. PMID- 1912534 TI - Imprisonment and tuberculosis in HIV-infected women. AB - The incidence of concomitant infections of tuberculosis (TB) and HIV in the same subject is on the increase, especially among inmates of jails and correctional institutions. The investigator examined the medical records of a sample of HIV positive women prisoners for the presence of TB, and compared them to a sample of HIV-positive women who were not prisoners. Tuberculosis was found to be related to HIV-positive women prisoners (X2 (1, N = 56) = 4.62, p less than .04). The nosocomial spread of TB among HIV-positive women prisoners has an exponential potential for increase, not only to other prisoners, but to caretakers and to the overwhelmed communities to which they are released. Their infants and children are at risk for both infections. Nurses who work with HIV-positive patients, especially those with a recent prison history, drug addiction, or homelessness are at increased risk for contracting tuberculosis from their patients, often of the drug-resistant type. PMID- 1912535 TI - [Telecommunication--a chance for radiology]. PMID- 1912536 TI - [The accuracy of plain-film radiology in demonstrating the shadows of the pneumatic spaces of the skull--a comparison with computed tomography]. AB - The accuracy of plain-film radiography in the diagnosis of opacities of the pneumatic system of the skull was evaluated in 302 patients in comparison with computed tomography. Plain films were performed using standard projections (Schuller, Stenvers, NNH o.n., paranasal sinus). Concerning the paranasal sinuses sensitivity of plain film radiography ranged from 36.7 to 66.4% depending on localisation. In the mastoid, a sensitivity of only 35% was found. Specificity was high (90% and over) with the exception of the maxillary sinus (82%). More sensitive, noninvasive diagnostic imaging techniques are indicated in the following conditions: therapy-refractory opacification of one sinus, indeterminate otological symptoms in the presence of a low pneumatized mastoid, and definitive exclusion of infectious foci in the pneumatic system of the skull. PMID- 1912537 TI - [Varicosis orbitalis. Its demonstration by color-coded Doppler sonography and computed tomography]. AB - Three patients with intermittent exophthalmos were studied by computed tomography (CT) and colour-coded Doppler sonography (CCDS). By CT the possible diagnosis of an orbital varix was established. CCDS, however, with the dynamic evaluation and realtime direct imaging of flow and the possibility of examination in different positions facilitated the diagnosis of this orbital vascular disorder without the need for any contrast material. This technique may prove to be a useful adjunct to computed tomography for the evaluation of suspected vascular lesions of the orbit. Surgery confirmed the diagnosis in all patients. PMID- 1912538 TI - [NMR tomographic diagnosis with Gd-DTPA in HIV-associated diseases in the head neck area]. AB - In a prospective study 21 patients suffering from HIV-1 infection underwent MR imaging. The following tumours were found: eight Kaposi's sarcomas, four lymphomas, two squamous-cell carcinomas, and three cases of lymphoid hyperplasia. Furthermore, three cases with lymphoepithelial cysts and one case of inflammatory changes of the parotid glands were studied. Optimal diagnostic results were obtained by using T1- and T2-weighted sequences plain and Gd-DTPA enhanced. Different signal intensities enabled the differentiation of lesions such as inflammation, lymphomas and lymphoid hyperplasia. Besides clinical examination modalities, MR imaging proves to be an important tool in investigating solid, cystic or inflamed processes in HIV-positive patients in the head and neck area. PMID- 1912539 TI - Assessing non-resectability of lung cancer. The value of thoracic computed tomography. AB - To investigate whether the assessment of resectability of lung cancer can be reliably made on the basis of computed tomography (CT), the thoracic CT scans of 96 lung cancer patients who were operated on, and in whom the tumour was classified to be of stage III at preoperative CT or at thoracotomy, were analysed. Of the patients, 58 underwent complete resection of the tumour, whereas thoracotomy resulted in non-complete resection or exploration only in 38 cases. Overlapping of the CT findings in the groups of complete and non-successful resection was observed. The majority of tumours with apparent growth to the carina, trachea, oesophagus or great vessels at CT were completely resected. Tumours that only bordered on the pleura could not be distinguished from those with pleural invasion. Mediastinal lymph node enlargement did not always mean metastatic spread. We conclude that there is no definite sign that identifies non resectability of lung tumours, and a certain proportion of non-curative thoracotomies must be accepted. PMID- 1912540 TI - [Digital peripheral angiography with pace shifting and subtraction. Comparison with the standard procedure]. AB - In a prospective randomised study including 60 patients digital peripheral angiography with stepping and subtraction (DPSA) was compared to DPA without subtraction (DPA), DSA without stepping and conventional angiography. Using conventional angiography, complementary series were necessary in 8 out of 20 patients. This number could be reduced to 3 out of 20 patients using DPSA and DSA respectively. Examination time could thus be shortened by about 20%. The amount of contrast medium could also be reduced by 15 to 20%. Both digital subtraction techniques supplied superior image quality especially in the lower limb in comparison with conventional and digital peripheral angiography without subtraction. X-ray exposure was similar for conventional angiography and DPSA. DSA without subtraction revealed a three times increased dose. Our results indicate that DPA with the possibility of image subtraction is a desirable new technique and might become the method of choice in peripheral angiography in the future. PMID- 1912541 TI - [The percutaneous catheter drainage of pancreatic pseudocysts]. AB - The results of CT/US-guided percutaneous drainage in 35 patients with pancreatic pseudocysts are reported. 27 patients recovered without surgery and no further treatment was required. 8 patients required a subsequent surgery due to recurrence. The role of CT/US-guided percutaneous drainage in pancreatic pseudocysts as well as an analysis of the technical aspects associated with a successful procedure are discussed. Although US may be used, we believe CT is safer and allows more precise localisation and guidance in the treatment of pseudocysts. PMID- 1912542 TI - [Obstructive jaundice: its histological diagnosis by percutaneous endoluminal bile duct biopsy]. AB - 32 forceps biopsies were performed in 30 patients with obstructive jaundice during percutaneous transhepatic biliary drainage procedures. In one patient an adequate specimen could not be obtained. In 25 of the remaining 31 cases diagnosis was confirmed histologically (malignant tumours: n = 22, benign stricture: n = 3). In 6 patients false-negative results were obtained. Transluminal biopsy is an easily performed adjunct to percutaneous transhepatic diagnostic interventions with minimal additional discomfort for the patient. In many cases percutaneous needle biopsy can be avoided. Forceps biopsy enables nonoperative histological diagnosis of small carcinomas of the bile ducts. PMID- 1912543 TI - [Abdominal organ-transcending tumors with special reference to peritoneal carcinosis. CT versus the surgical site]. AB - In 41 patients with a histologically confirmed peritoneal carcinomatosis (n = 29) or lymphangiomatosis (n = 12) the preoperative CT investigations of the abdomen were compared with intraoperative findings. CT findings were differentiated between direct or indirect signs. The sensitivity of the various CT signs of peritoneal carcinomatosis or lymphangiomatosis was between 66 and 100%. Abdominal CT studies proved to be a reliable preoperative method if the findings were examined closely. A precise review even of indirect signs is of high diagnostic value. PMID- 1912544 TI - [The methods and place of digital subtraction arthrography of the hip in detecting endoprosthesis loosening]. AB - Digital subtraction arthrography (DSAr) of the operated hip is presented and compared to nuclide bone scan and plain radiograph. Surgical proof was obtained in 47 patients. In the evaluation DSAr proved to be superior to nuclide bone scan and plain radiograph. DSAr had the best predictive value in the diagnosis of loosening of a prosthesis. In contrast to conventional arthrography there is a better differentiation between the contrast medium, the prosthesis, the acrylic cement and the bone by using DSAr. In addition DSAr presents the advantage of postprocessing, especially pixel shift. PMID- 1912545 TI - [The radiological diagnosis of the male breast. Mammography, sonography and pathohistological correlation]. AB - 61 men with breast enlargement underwent mammography; complementary sonography was performed in 34 cases. Diagnoses included gynaecomastia in 53 cases, pseudo gynaecomastia in 9 cases, 3 carcinomas, 2 inflammatory lesions and 1 lipoma. Gynaecomastias of up to four month's duration are histologically of the florid type and show a nodular or nodular-dendritic mammographic pattern; sonography usually demonstrates a focal hypo-echogenic area. Gynaecomastias of longer duration representing the fibrous type show mammographically a dendritic or diffuse pattern and sonographically a hyper-reflexive breast parenchyma. Mammography and sonography can differentiate reliably true gynaecomastia from pseudo-gynaecomastia. Gynaecomastia and especially inflammatory lesions may not always be readily differentiated from carcinoma. Sonography can be helpful by demonstrating hyper-reflexive glandular tissue, whereas carcinomas are usually hypoechoic. PMID- 1912547 TI - [More rapid MRT with T2-weighted spin-echo sequences through variation of the flip angle]. AB - In the present study the influence of the flip angle on image contrast in spin echo imaging was investigated. It was evaluated, whether variation of the flip angle allows for shorter repetition and imaging times in T2-weighted spin echo sequences. 10 patients with cerebral white matter lesions were investigated with an 1.5 Tesla whole body tomograph using a conventional double-spin echo sequence (TR = 2500 ms, TE = 15 and 70 ms) and time-optimized double-spin echo sequences (TR = 1900 ms, TE 15 and 70 ms) at flip angles of 90, 80, 70, 60 and 50 degrees. A reduction of the flip angles resulted in a decrease of T1-weighting and a relative increase of T2-weighting of the images. Despite the reduced repetition time at a flip angle of 70 degrees visually and quantitatively assessed contrast between lesions and brain as well as image artifacts of the time-optimized sequence were comparable to the conventional spin echo sequence; however, imaging time was shortened about 25%. PMID- 1912546 TI - [The rapid magnetic resonance tomography measurement of the contrast medium dilution kinetics (gadolinium-DTPA) in a circulatory phantom]. AB - We studied first-pass MRI contrast dilution to compute flow and volume of distribution in a realistic flow phantom. Pulsatile flow was provided by a one chamber artificial heart. Physiological stroke volume, rate, pressure, and flow were adjustable. An elastic tube with dimensions similar to that of the human aorta was imaged at a rate of 2.4 Hz. After contrast injection, an initial increase in signal intensity was followed by a decrease. Signal-intensity time plots demonstrated slightly skewed curves as expected from dispersion theory. After calibration at different gadolinium-DTPA concentrations, signal intensities were converted into true gadolinium concentrations, and flow was calculated from the concentration-time curves. Flow was varied between 2.5 and 10.0 l/min and a significant correlation was found between the MRI estimate and true flow. Volume of distribution between injection and detection site was reliably estimated. This study demonstrates rapid 2-D imaging of a paramagnetic contrast bolus in a realistic flow phantom. Reliable estimates of flow and volume are obtained. PMID- 1912548 TI - [A nontraumatic compartment syndrome of both lower legs resulting from acute rhabdomyolysis]. PMID- 1912549 TI - [Multiple atheromas with symmetrical localization on both thighs in the sub inguinal region]. PMID- 1912550 TI - [The computed tomographic manifestation of diffuse visceral lymphangiomatosis]. PMID- 1912551 TI - [The radiological detection of mesenteric chylous cysts]. PMID- 1912552 TI - Structure-function relationships of epidermal growth factor modules in vitamin K dependent clotting factors. PMID- 1912553 TI - P53 gene mutations in acute myeloid leukemia with 17p monosomy. AB - We looked for mutations of exons 5 to 8 of the P53 gene in 10 patients with acute myeloid leukemia (AML) and 17p monosomy, and 36 patients with AML and no cytogenetic abnormalities of 17p. DNA was analyzed by polymerase chain reaction, single-strand conformation polymorphism analysis, and nucleotide sequencing. Four of the 10 patients with 17p monosomy showed point mutation, single-nucleotide deletion, or insertion in exons 7 or 8. By contrast, only 1 of the 36 patients with AML and no cytogenetic abnormalities of 17p showed a mutation of the P53 gene in exons 5 to 8 (P less than .01). These results suggest that alterations of the P53 gene may have a role in leukemogenesis in some cases of AML. The fact that P53 gene mutations occurred more often in patients with 17p monosomy seems to support the "recessive" model of tumor suppressive activity of the P53 gene rather than the "dominant" model, in which alteration of only one allele is sufficient for the development of malignancy. PMID- 1912554 TI - Pharmacologic doses of recombinant human erythropoietin in the treatment of myelodysplastic syndromes. AB - Twenty patients with myelodysplastic syndromes (MDS) entered a randomized, placebo-controlled, double-blind trial designed to evaluate the efficacy and toxicity of high doses of recombinant human erythropoietin (rhEPO). Patients completing the trial were eligible to receive rhEPO as part of an open-label study. Eighteen patients were transfusion dependent; 10 had refractory anemia (RA), and 10 had refractory anemia with ringed sideroblasts (RARS). A response to rhEPO was defined as an increase in hematocrit of 4 percentage points or more over baseline, or the elimination of all transfusions with the hematocrit stable at the baseline level. In the double-blind trial, 1 patient (12.5%) receiving rhEPO responded, as compared with no responses in the placebo group. Overall, responses occurred in 4 of 17 patients (24%) receiving rhEPO at a dose of 1,200 to 1,600 U/kg intravenously (IV) twice weekly. Changes in granulocyte or platelet counts were not observed. Despite the administration of high doses of rhEPO, toxicity attributable to rhEPO was not observed in either the double-blind or open-label study. Response to rhEPO was not significantly related to age, gender, type of MDS, time since diagnosis, time since initiation of transfusion therapy, or baseline serum EPO. These studies indicate that rhEPO can be administered safely in very high doses to patients with MDS and that 24% of these patients will respond with increased erythropoiesis. PMID- 1912555 TI - Prolonged, continuous treatment of hairy cell leukemia patients with recombinant interferon-alpha 2a. AB - Interferons are not curative in hairy cell leukemia (HCL), and retreatment is necessary in most patients whose therapy is stopped. In an attempt to maintain or improve responses, we administered recombinant interferon-alpha 2a (rIFN-alpha 2a) continuously to patients with HCL who initially responded to this therapy. Of 53 evaluable patients enrolled in this study, 32 have received rIFN-alpha 2a continuously for a median of 5 years. Patients received 3 million units of rIFN alpha 2a subcutaneously (SC) daily for 6 months, followed, in responding patients, by the same dose three times weekly. Twenty-one patients (40%) discontinued IFN after a median of 29 months, seven of whom developed resistant disease in association with anti-IFN antibodies. Treatment produced high response rates: complete response plus partial response (CR + PR) = 40 of 53 (76%), CR + PR + minor response (MR) = 43 of 53 (82%), with no differences in response rates between patients with and without splenectomy. Sixteen patients who had MR at 18 months had PR with prolonged treatment, nine of whom had a significant further reduction in the hairy cell infiltrate in the bone marrow (BM). The median granulocyte and platelet counts have continued to increase and the median serum soluble interleukin-2 receptor (sIL-2R) level has continued to decrease with prolonged treatment. Two patients developed erythrocytosis that may be treatment related, but no other new toxicities were noted with prolonged treatment. We conclude that prolonged, continuous rIFN-alpha 2a treatment has acceptable toxicity, is not associated with late development of IFN resistance, and results in continued hematologic improvement with time on treatment. PMID- 1912556 TI - A randomized controlled trial of recombinant interferon-alpha in chronic hepatitis C in hemophiliacs. AB - Chronic liver disease associated with hepatitis C virus (HCV) is an important cause of morbidity and mortality in hemophilia. We have used recombinant interferon alpha-2b (IFN alpha-2b) in a randomized controlled liver biopsy trial to treat hemophiliacs with chronic hepatitis. Eighteen patients entered the study, 16 of whom were subsequently shown to have antibodies to the HCV. All underwent liver biopsy at entry and were randomized to either treatment with self administered IFN alpha-2b, 3 million units subcutaneously thrice weekly (n = 10) or no treatment (control group) (n = 8). Nine subjects had chronic active hepatitis, seven had chronic persistent hepatitis, and two had cirrhosis. Twelve months after entry into the study 17 patients underwent a second liver biopsy. All biopsies were coded, assessed, and scored according to the histologic severity of the liver disease. Ten patients were administered IFN for 1 year, and in four patients normalization of alanine aminotransferase (ALT) occurred compared with none in the untreated group. After the second liver biopsy, six of the eight initial no-treatment patients were treated with interferon 3 million units thrice weekly for 6 months, and normalization of ALT was seen in five patients. Biochemical relapse within 4 months of stopping IFN occurred in one of four patients treated for 1 year and in four of five patients treated for 6 months. IFN treatment was well tolerated. Although the histologic scores of the two groups were similar at entry into the study, after 12 months the biopsy appearances in the treated group were significantly improved compared with the controls (P less than .01). Histologic improvement was noted in the three interferon-treated human immunodeficiency virus antibody-positive patients and also in other patients who had no biochemical response. We conclude that low-dose recombinant IFN alpha is effective in normalizing transaminases and improving the histologic appearances in at least 50% of hemophiliacs with chronic hepatitis C. PMID- 1912557 TI - Regulation of interleukin-4 receptors on murine myeloid progenitor cells by interleukin-6. AB - Interleukin-4 (IL-4) is a T-cell-derived cytokine that regulates induction of proliferation of resting B cells and acts on various other immunocompetent cells, such as monocytes/macrophages and mast cells, as well as hematopoietic progenitor cells. On hematopoietic progenitor cells, cooperation with another cytokine (such as granulocyte-macrophage colony-stimulating factor [GM-CSF], G-CSF, IL-3, or IL 6) is required to render the cells responsive to IL-4. The present study was undertaken to determine if such an interaction entails induction of IL-4 receptor (IL-4R) expression. Using the murine myeloid leukemia M1 cell line and mature, bone marrow (BM)-derived macrophages, we investigated whether IL-4R expression can be induced during differentiation. We detected no high-affinity IL-4R on the surface of either cell, but with exposure to IL-6 a significant induction of IL 4R was measured on both cell types by fluorescence-activated cell sorter analysis. This increase in IL-4R was first noted 6 hours after exposure of the cells to IL-6 and continued to increase up to 48 hours. By RNase protection analysis we found that the expression of IL-4R mRNA also appeared within 6 hours, continuing to increase up to 48 hours. Nuclear run-on assays showed that this increase in steady-state level of IL-4R mRNA results from a transcriptional activation of the IL-4R gene. These data suggest that regulation of IL-4R expression by IL-6 is under transcriptional control. PMID- 1912558 TI - Enhanced repopulation of murine hematopoietic organs in sublethally irradiated mice after treatment with ciprofloxacin. AB - We analyzed the effect of ciprofloxacin, fleroxacin, and ceftazidime on production of colony-stimulating factors (CSF) by cultured murine spleen cells in the presence of pokeweed mitogen (PWM). Ciprofloxacin at concentrations of 5 to 10 micrograms/mL in concert with PWM stimulated CSF production by cultured spleen cells. A 3.5-fold increase in the number of CFU-C was observed in the presence of ciprofloxacin-PWM spleen conditioned medium (SCM) as compared with control cultures exposed to PWM-SCM only. Antimurine GM-CSF and antimurine interleukin-3 (IL-3) antibodies inhibited colony formation stimulated by PWM-SCM or ciprofloxacin-PWM-SCM. Fleroxacin and ceftazidime at concentrations of 1 to 100 micrograms/mL and ciprofloxacin at high concentration (greater than 10 micrograms/mL) either did not affect CSF production by spleen cells or had an inhibitory effect. In vivo treatment of sublethally irradiated (650 rad) mice with ciprofloxacin (15 mg/kg per dose three times daily for 5 days) resulted in an increased number of myeloid progenitors in the spleen and bone marrow (BM) of treated mice. In contrast, treatment with ceftazidime did not affect progenitor cell numbers. On days 4 and 8 postirradiation ciprofloxacin-treated mice had a 2.3- and 3.8-fold increase, respectively, in the number of CFU-C in the BM. The number of CFU-C in the spleen did not increase on day 4 postirradiation, but on day 8, the number increased 1.7-fold. On day 4 postirradiation, sublethally irradiated mice treated with ciprofloxacin had a higher WBC count, RBC count, and hemoglobin level as compared with ceftazidime- and saline-treated mice. Twenty four days postirradiation, 45% of saline-treated mice (20 of 44), and 35% of ceftazidime-treated mice (8 of 23) died, as compared with 13% (5 of 38) of ciprofloxacin-treated mice (P less than .05). These studies indicate that ciprofloxacin may have an immune-enhancing effect on the hematopoietic system in neutropenic mice. PMID- 1912559 TI - Adducin in erythrocyte precursor cells of rats and humans: expression and compartmentalization. AB - Adducin is a calmodulin-binding protein involved in the assembly of the erythrocyte membrane skeleton. To investigate the expression of adducin during human erythropoiesis, we performed immunofluorescence studies on smears of cultured human erythroblasts. Adducin immunoreactivity was found in the early stages of erythropoiesis. Proerythroblasts were the first erythroid precursor cells positive for adducin. The adducin signal was very similar to the signal of erythroid beta-spectrin in that both proteins lined the membrane of erythroid precursor cells. Cell fractionation experiments were performed to further analyze the intracellular distribution of adducin in erythroid cells. In erythroblasts, about 60% of total cellular adducin appeared in the Triton-soluble fraction. In reticulocytes, the Triton-soluble fraction decreased to 30% of total reticulocyte adducin. Erythrocytes had no detectable amount of adducin in the Triton-soluble pool. Instead, adducin was quantitatively bound to the Triton-insoluble erythrocyte cytoskeleton. Our results suggest that adducin is expressed early in the development of the erythrocyte membrane skeleton, whereas stable assembly onto the membrane skeleton does not occur before the final stages of mammalian erythropoiesis. PMID- 1912560 TI - Infection of megakaryocytes by human immunodeficiency virus in seropositive patients with immune thrombocytopenic purpura. AB - Twenty-one human immunodeficiency virus (HIV)-positive patients, including 11 acquired immunodeficiency syndrome (AIDS)-free patients with immune thrombocytopenic purpura (ITP), were studied to determine whether the megakaryocytic/platelet lineage was infected by HIV. Because purification of platelets did not reach a level sufficient for unequivocal results by the polymerase chain reaction, in situ hybridization was thus performed. Purified marrow megakaryocytes (MK) from 10 HIV-infected ITP patients were studied using a 35S HIV riboprobe, antisense of an HIV ENV sequence. HIV transcripts were clearly detected in MK from five of these 10 patients, although heterogeneity among MK was observed. In three of these five cases, small amounts of HIV glycoproteins were detected in MK by means of immunofluorescence. In addition anti-HIV antibodies could be eluted from platelets of all patients. In contrast, HIV transcripts were not detected in MK derived from colony-forming units-MK (CFU-MK) cultured in suspension, suggesting either that MK are infected by HIV during terminal differentiation or that HIV-infected CFU-MK are unable to differentiate in vitro. In conclusion, this study suggests that HIV infection of MK may be implicated in the pathogenesis of thrombocytopenia of HIV-positive patients. PMID- 1912561 TI - Platelet activation by a synthetic hydrophobic polymer, polymethylmethacrylate. AB - Platelets adhere to artificial surfaces in the initial stage of thrombus formation, but the subsequent steps in signal transduction that lead to platelet activation by artificial surfaces are not understood. When 0.325-micron diameter beads composed of a hydrophobic polymer, polymethylmethacrylate (PMMA), were added to gel-filtered aequorin-loaded platelets suspended in media containing Ca2+, the platelets aggregated; addition of fibrinogen was not required. Platelet aggregation was preceded by an increase in cytoplasmic Ca2+ and was accompanied by phosphorylation of the 47-Kd substrate of protein kinase C (PKC), 5 hydroxytryptamine (5-HT) release, and accumulation of phosphatidic acid. All these effects were partially inhibited by apyrase and aspirin. Monoclonal antibodies (MoAbs) 7E3 and M148 and the synthetic peptides RGDS and fibrinogen gamma chain fragment 400-411, all of which bind to the platelet fibrinogen receptor glycoprotein IIb-IIIa (GPIIb-IIIa) and inhibit fibrinogen binding, prevented PMMA-induced aggregation but did not inhibit the Ca2+ increase. Chymotrypsin-treated platelets aggregated after addition of fibrinogen, but not PMMA. We conclude that platelets interact initially with PMMA at membrane sites other than those required for fibrinogen binding, leading to activation of membrane phospholipases and PKC, an increase in cytoplasmic Ca2+, release of 5 HT, ADP, and fibrinogen from storage granules, and to platelet aggregation. PMID- 1912562 TI - Human platelet-specific antigen, Siba, is associated with the molecular weight polymorphism of glycoprotein Ib alpha. AB - Platelet-specific antigen Sib(a) has been highly implicated in the pathogenesis of refractoriness to human leukocyte antigen (HLA)-matched platelet transfusions in Japan. We provide evidence that the Sib(a) antigen is located on the glycoprotein (GP) Ib alpha and has a close association with the molecular weight (mol wt) polymorphism of GPIb. In modified antigen-capture ELISA (MACE), anti Sib(a) antibody reacted only with GPIb/IX held by a murine anti-GPIb/IX monoclonal antibody (MoAb). The reactivity of anti-Sib(a) antibody to Sib(a) positive (Sib(a+)) platelets was abolished after they were treated with Serratia marcescens protease. Platelets from 50 healthy volunteers were semiquantitatively phenotyped for Sib(a) antigen by MACE and divided into three distinct groups: strongly positive, positive, and negative. They were also analyzed by sodium dodeyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and periodic acid silver staining for mol wt polymorphism of GPIb, phenotyped as A, B, C, or D. Without exception, Sib(a+) platelets showed larger phenotypes (A or B). Removal of sialic acid from Sib(a+) platelets did not reduce the binding of anti-Sib(a). Finally, anti-Sib(a) antibody specifically immunoprecipitated A and B phenotypes of GPIb from Sib(a+) platelets. Thus, Sib(a) antigen evidently is located in the region of glycocalicin that is present only on the A and B phenotypes of GPIb. PMID- 1912563 TI - Duplication of a methionine within the glycoprotein Ib binding domain of von Willebrand factor detected by denaturing gradient gel electrophoresis in a patient with type IIB von Willebrand disease. AB - von Willebrand disease (vWD) type IIB is characterized by an increased reactivity of von Willebrand factor (vWF) with platelets and a lack of large multimers. Exon 28 of the vWF gene encodes for functional domains involved in the binding of vWF to GPIb, and it is presumed that the defects in type IIB vWD lie within or adjacent to these functional domains. We screened overlapping DNA fragments generated by the polymerase chain reaction (PCR) that spanned the 1,379 bp of exon 28 of a type IIB vWD patient using denaturing gradient gel electrophoresis (DGGE). To increase the power of DGGE to detect base changes, we used the PCR to attach a G + C-rich sequence. In the type IIB patient, a DNA fragment at the 5' end of exon 28 demonstrated homoduplex and heteroduplex complexes after DGGE, a pattern characteristic of heterozygous genes after melting and reannealing during the PCR. Sequencing of the cloned insert from the patient showed a duplication of an ATG in one gene coding for a Met at amino acids 540 to 541 in the mature vWF subunit. This duplication leads to three consecutive methionines in the patient's sequence. The duplicated Met resides within a disulfide bond loop proposed to be important in the function of the GPIb binding domain of vWF. The patient's nephew, who also has type IIB vWD, showed the same duplicated codon, linking the defect to the abnormal phenotype in this family. These nucleotide changes were not found in 100 chromosomes analyzed either by DGGE or hybridization with an allele specific oligonucleotide containing the duplicated ATG codon. In addition, the same oligonucleotide hybridized only to DNA from type IIB vWD individuals and not to DNA from normal members of the family. Therefore, we conclude that this duplicated Met modifies the GPIb binding domain of vWF and causes type IIB vWD in this family. PMID- 1912564 TI - Fibrinogen Ledyard (A alpha Arg16----Cys): biochemical and physiologic characterization. AB - Fibrinogen Ledyard was discovered in a 10-year-old boy with a mild bleeding history. His father had the same defect and a bleeding history after surgery. Both patients were heterozygous. The plasma fibrinogen concentration was normal immunologically (335 mg/dL) and very low functionally (52 mg/dL). Purified fibrinogen Ledyard had a prolonged polymerization, which was somewhat corrected by addition of Ca2+ ions. High performance liquid chromatography (HPLC) analyses of the fibrinopeptides released by thrombin showed 1 mol of fibrinopeptide A (FPA) and 2 mol of fibrinopeptide B (FPB) released per mole of fibrinogen Ledyard. Steady-state kinetic parameters were evaluated for release of FPA by thrombin. When the concentration of fibrinogen Ledyard was corrected to 50% of total protein, because only 50% of fibrinogen Ledyard can release FPA, the kinetic constants were similar to those of control fibrinogen (Km = 7.5 mumol/L for A alpha chain, kcat = 54 s-1). This finding indicates that the cleavage site of the A alpha chain in these abnormal molecules may not interact with the catalytic site of thrombin. The three chains of fibrinogen Ledyard were isolated on reverse-phase C4-HPLC. The sequence of the amino terminus of A alpha chain showed that Arg in position 16 was replaced by Cys in the abnormal molecules. Approximately half of fibrinogen Ledyard (52%) was clotted by reptilase, suggesting that fibrinogen Ledyard may consist of 50% normal homodimers (A alpha Arg16 . A alpha Arg16) and 50% abnormal homodimers (A alpha Cys16 . A alpha Cys16). Abnormal molecules could form disulfide bond between the A alpha Cys16 residues. Thus, the abnormal molecules have a different structure that does not bind to thrombin. Probably the abnormality of polymerization of fibrinogen Ledyard results from the interaction of the abnormal molecules with normal fibrin monomers, so that the growth of fibrin protofibrils is inhibited. This abnormal fibrinogen supports adenosine diphosphate-induced platelet aggregation in a normal manner. PMID- 1912565 TI - Chloroquine attenuates hemorrhagic shock-induced suppression of Kupffer cell antigen presentation and major histocompatibility complex class II antigen expression through blockade of tumor necrosis factor and prostaglandin release. AB - Hemorrhagic shock suppresses the ability of Kupffer cells (KC) to present antigen and express the major histocompatibility complex class II (Ia) antigen. These alterations are concomitant with an enhanced release of cytokines (tumor necrosis factor [TNF], interleukin-1 [IL-1], IL-6) and prostaglandin E2 (PGE2) by KC after hemorrhagic shock. The aim of this study was to determine whether chloroquine (CQ) administration in vivo before or after hemorrhage affects the altered cytokine and PGE2 release by KC as well as the capacity of KC to present antigen and express Ia. To study this, C3H/HeN mice were bled to and maintained at a mean arterial blood pressure of 35 mm Hg for 60 minutes, followed by fluid resuscitation. Chloroquine (10 mg/kg body weight) was injected intramuscularly 2 hours before or during resuscitation following shock. The administration of CQ led to a significant reduction in the hemorrhage-induced elevation of TNF, IL-6, and PGE2 release by KC; however, IL-1 secretion was not affected by CQ. In addition, CQ treatment abolished the hemorrhage-induced increase in circulating TNF and IL-6. These changes in cytokine and PGE2 release following CQ administration correlated with a significant enhancement of the antigen presenting capacity of KC. No differences were observed between pretreatment and posttreatment with CQ. Our data indicate that CQ selectively inhibits the release of TNF, IL-6, and PGE2 by KC, while IL-1 secretion was unaffected. Because the reduction of these inflammatory mediators was concomitant with a significant improvement of KC capacity to present antigen and express Ia, we propose that TNF, IL-6, and PGE2 play a pivotal role in the induction of posthemorrhage immunosuppression. Furthermore, the data suggest that the suppression of KC functions occurs during or after resuscitation, because posttreatment with CQ was as effective as pretreatment. Additional studies indicated that the survival of animals after hemorrhage and sepsis was significantly increased by posttreatment of hemorrhaged mice with CQ. Thus, CQ, because of its unique ability to selectively inhibit the release of inflammatory cytokines and prostaglandins, represents a potent immunomodulating agent in the treatment of conditions associated with increased cytokine release and for decreasing the mortality from sepsis after hemorrhage. PMID- 1912566 TI - Establishment of an interleukin-3-dependent leukemic cell line from a patient with chronic lymphocytic leukemia in the acute phase. AB - A novel human leukemic cell line, TMD2, which proliferates dependently on interleukin-3 (IL-3), was established from the peripheral blood (PB) of a patient with chronic lymphocytic leukemia (CLL) in the acute phase. After 8 years of the chronic phase of CLL, lymphoblastoid cells appeared and became dominant in the PB. After repeated subcultures of the patient's PB cells in the acute phase, lymphoblastoid cells have proliferated actively in the presence of recombinant human IL-3, and the TMD2 cell line has been established. The lymphoblastoid cells in acute phase and TMD2 cells proliferated dependently on IL-3, whereas growth of the small lymphocytes in chronic phase was not supported by IL-3. Other ILs (IL 1, 2, and 4 through 6) or CSF did not support the growth or survival of TMD2 cells. The existence of high-affinity receptors for IL-3 was shown on TMD2 cells (binding sites 88 per cell, Kd = 76.9 pmol/L). DNA extracted from the small lymphocytes in the chronic phase, the lymphoblastoid cells in the acute phase, and TMD2 cells showed the same rearrangement pattern of the immunoglobulin heavy chain gene. Therefore, these cells were considered to have originated from the same clone. These results imply that a genetic event that caused the responsiveness to IL-3 in the cell of the chronic phase caused the acute transformation of CLL in this patient. We consider that TMD2 cell line is valuable as a model of cells of CLL in the acute phase and as a tool for studying the signal transduction system of IL-3. PMID- 1912567 TI - S100-positive, T-cell chronic lymphoproliferative disease: an aggressive disorder of an uncommon T-cell subset. AB - S100-positive T lymphocytes account for less than 3% of peripheral blood T cells. Rare cases of S100-positive T-cell lymphoma have been previously described. We report four such cases of S100-positive T-cell chronic lymphoproliferative disease. In all cases, hepatosplenomegaly was observed, without prominent lymphadenopathy. Central nervous system (CNS) involvement by the leukemic cells was suggested in three cases by physical symptoms and confirmed in two cases by cerebrospinal fluid studies. Despite treatment, three patients died at 3, 6, and 8 months after diagnosis. Although there was a leukemic presentation, only minimal bone marrow infiltration was evident. Splenectomy showed red pulp infiltration. Liver and lymph node biopsies showed sinusoidal leukemic involvement. In all cases, the leukemic cells expressed mature T-cell- and natural killer cell-associated antigens. Cytoplasmic S100 was detected in the leukemic cells in the blood, spleen, liver, and lymph node. Southern blot studies in two cases showed T-beta, T-gamma, and T-delta gene rearrangements. RNA Northern blots showed T-alpha and T-beta chain transcripts with no T-gamma or T delta RNA identified. Southern blot analysis showed no hybridization to probes specific for Epstein-Barr virus, cytomegalovirus, human immunodeficiency virus-1, or human T-cell lymphotropic virus type-1. These findings show that S100-positive T-cell chronic lymphoproliferative disorder is an aggressive, extramedullary based disease frequently associated with CNS involvement and characterized by short survivals. PMID- 1912568 TI - Phagocytosis of phenylhydrazine oxidized and G-6-PD-deficient red blood cells: the role of cell-bound immunoglobulins. AB - In this study, the role of Igs in the recognition and removal of oxidatively damaged human red blood cells (RBCs) was investigated. Phagocytosis of normal RBCs exposed to the oxidative hemolytic agent phenylhydrazine (Phz) and of glucose-6-phosphate dehydrogenase (G6PD)-deficient RBCs by murine macrophages was examined. A 40-fold increase in phagocytosis of RBCs treated with 3 mmol/L Phz was obtained both in the absence and presence of autologous serum, indicating that binding of autologous antibodies to the oxidized cells is not essential for phagocytosis. Yet, a basal number of IgG molecules was found to be present on the RBCs, as determined both by binding of 125I protein A and fluorescein isothiocyanate-antihuman Ig to the cells. Macrophage Fc receptors were found to be involved in the recognition of the RBCs, because phagocytosis was partially inhibited by incubating macrophages with bovine serum albumin (BSA) anti-BSA complexes, aIg (aggregated Igs), and anti-Fc receptor II monoclonal antibodies. Galactose/mannose inhibited phagocytosis of oxidized RBCs additively to aIg. Because phagocytosis was decreased when Phz-RBCs were incubated with F(ab')2 fragments of antihuman antibodies, it is suggested that the basal amount of Igs bound to the cells plays a role in the recognition of Phz-RBCs. G6PD-deficient RBCs were recognized and phagocytosed by murine macrophages without preexposure to oxidants in vitro (mean of 19 RBCs/100 macrophages). This phagocytosis was not affected by the addition of serum and was inhibited by incubating macrophages with galactose/mannose and the various Fc receptor blockers. A positive correlation between hemoglobin content and the number of cell-bound Igs to each patient erythrocytes was found. These results support the involvement of both an Fc and a lectin-like macrophage receptor in the recognition and phagocytosis of Phz-oxidized and G6PD-deficient RBCs and suggest opsonization as a possible physiologic process for the removal of severe damaged RBCs. PMID- 1912569 TI - Cellular myosin heavy chain in human leukocytes: isolation of 5' cDNA clones, characterization of the protein, chromosomal localization, and upregulation during myeloid differentiation. AB - We have isolated 5' cDNA clones encoding a member of the cellular myosin heavy chain gene family from human leukocytes. The predicted amino acid sequence shows 93% identity to a chicken cellular myosin heavy chain, 76% to chicken smooth muscle, and 40% to human sarcomeric myosin heavy chain. The mRNA is expressed as a 7.4- to 7.9-kb doublet in many nonmuscle cells, and is upregulated in myeloid cell lines on induction from a proliferating to a differentiated state. Antisera raised against a peptide made from the predicted amino acid sequence specifically reacts with a 224-Kd polypeptide in leukocyte cell lines, and the protein is also upregulated during the induction of monocytic and granulocytic differentiation in these cells. The gene for this cellular myosin heavy chain maps to chromosome 22, bands q12.3-q13.1, demonstrating that it is not located in the previously described sarcomeric gene clusters on chromosomes 14 and 17. This cellular myosin heavy chain may be a major contractile protein responsible for movement in myeloid cell lines because no mRNA for sarcomeric myosin heavy chain is detected in these cells. PMID- 1912570 TI - Interaction of Sp1 with the human gamma globin promoter: binding and transactivation of normal and mutant promoters. AB - We have analyzed the binding of Sp1, a ubiquitously expressed transactivator, to the promoter region of the gamma genes. Low-affinity Sp1 sites were found at -50 and -200. A high-affinity site was detected at -140, over the CACCC sequence. To analyze the function of these sites, Drosophila SL-2 cells, which lack Sp1, were cotransfected with an Sp1 expression plasmid and gamma globin promoter-CAT constructs. In these assays, the gamma promoter was significantly stronger in the presence than in the absence of Sp1. Thus, the three Sp1 sites in the gamma promoter allow binding as well as transactivation of the promoter. The majority of this transactivation was due to the strong binding site at -140 because introduction of a point mutation at -144 (CACCC----AACCC) reduced Sp1-dependent promoter strength by 57%. Analysis of the -200 region suggested that in the wild type promoter, Sp1 binding at this site contributes little to promoter strength. However, a point mutation (-198 T----C) associated with hereditary persistence of fetal hemoglobin (HPFH) dramatically increased the affinity of this site for Sp1 and significantly increased Sp1 dependent promoter strength in SL-2 cells. Three other point mutations associated with HPFH did not significantly affect the interaction of Sp1 with the -200 region. PMID- 1912571 TI - Single-nucleotide substitution in pyruvate kinase deficiency. PMID- 1912572 TI - Detection of differentiation in acute promyelocytic leukemia. PMID- 1912573 TI - A VH clonal deficit in human immunodeficiency virus-positive individuals reflects a B-cell maturational arrest. PMID- 1912574 TI - B-cell chronic lymphocytic leukemia: present status and future directions. French Cooperative Group on CLL. PMID- 1912575 TI - Allogeneic bone marrow transplantation for high-risk acute lymphoblastic leukemia during first complete remission. AB - Fifty-three patients with high-risk acute lymphoblastic leukemia (ALL) under age 50 with a histocompatible sibling donor received high-dose radiochemotherapy followed by allogeneic bone marrow transplantation (BMT). The high-risk factors used to identify the patients were: white blood cell count at initial presentation, cytogenetic abnormalities, age, extramedullary leukemic infiltration, and time from initial therapy to complete remission. Patients with one or more of the above risk factors who received BMT have a disease-free survival of 61% with a median follow-up of 66 months (range 11 months to 10.6 years), and an actuarial relapse rate of 10%. This study demonstrates that patients with high-risk ALL achieve a significant disease-free survival and cure rate with the use of allogeneic fully matched sibling BMT. However, a properly designed prospective study comparing the outcome of BMT with the best currently available chemotherapy data is required to define the ultimate role of BMT in this group of patients. PMID- 1912576 TI - Anemia and mast cell depletion in mutant rats that are homozygous at "white spotting (Ws)" locus. AB - Mice possessing two mutant alleles at the W or Sl locus are anemic and deficient in mast cells. These mouse mutants have black eyes and white hair. Because homozygous mutant rats at the newly found white spotting (Ws) locus were also black-eyed whites, the numbers of erythrocytes and mast cells were examined. Suckling Ws/Ws rats showed a severe macrocytic anemia and were deficient in mast cells. When bone marrow cells of normal (+/+) control or Ws/Ws rats were injected into C3H/He mice that had received cyclophosphamide injection and whole-body irradiation, remarkable erythropoiesis occurred in the spleen of +/+ marrow recipients but not in the spleen of Ws/Ws marrow recipients. When skin pieces of Ws/Ws embryos were grafted under the kidney capsule of nude athymic rats, mast cells did develop in the grafted skin tissues. Therefore, the anemia and mast cell deficiency of Ws/Ws rats were attributed to a defect of precursors of erythrocytes and mast cells. Because the magnitude of the anemia decreased and that of the mast cell deficiency increased in adult Ws/Ws rats, this mutant is potentially useful for investigations about differentiation and function of mast cells. PMID- 1912577 TI - Characterization of Ws mutant allele of rats: a 12-base deletion in tyrosine kinase domain of c-kit gene. AB - Homozygous mutant rats at the newly found white spotting (Ws) locus were anemic and deficient in mast cells and melanocytes. Because the phenotype of Ws/Ws rats resembled the phenotype of mice possessing a double-gene dose of mutant alleles at the W locus and because the c-kit gene was mapped at the W locus of mice, we characterized the c-kit gene of Ws/Ws rats. The authentic sequence of the rat c kit cDNA was determined by using a cDNA library prepared from the hippocampus of Sprague-Dawley rats. The c-kit cDNA of Ws/Ws and normal (+/+) control rats was obtained by reverse transcriptase modification of the polymerase chain reaction. When compared with the authentic sequence, a deletion of 12 bases was found in the c-kit cDNA of Ws/Ws rats. This change was shown to be a result of the deletion of the genomic DNA. Four amino acids encoded by the deleted 12 bases (ie, Val-Lys-Gly-Asn) were located at two amino acids downstream from the tyrosine autophosphorylation site in the c-kit kinase and were conserved not only in mouse and human c-kit kinases but also in mouse and human c-fms kinases (ie, receptors of colony-stimulating factor-1). Taken together, the Ws/Ws rat is the first characterized mutant of the c-kit gene in an animal species other than the mouse. PMID- 1912578 TI - Interleukin-6 supports human megakaryocytic proliferation and differentiation in vitro. AB - The effect of interleukin-6 (IL-6) on cells of human megakaryocyte (MK) lineage from cord blood was explored. In semisolid colony assays containing human plasma, a greater number of both MK colonies and cells per colony was seen in the presence of IL-6 and IL-3 than in the presence of IL-3 alone. This stimulatory effect of IL-6, observed on both small and large MK colonies, was completely eliminated by the addition of anti-IL-6 antibody to the culture. IL-6 alone had no effect on MK colony formation. In the primary culture, MKs showed larger cell size and DNA content in the presence of both IL-3 and IL-6 than IL-3 alone. The replating experiments using immature MKs grown in the presence of IL-3 showed that IL-6 significantly augmented both cell size and DNA content. This effect was also neutralized by an anti-IL-6 antibody. IL-3 had no tangible effect on MK differentiation. Synergism between IL-6 and IL-3 on MK differentiation was not confirmed. These results suggest that IL-6 is a synergistic factor in the proliferation of MK progenitors and a direct effector of differentiation of immature MKs on in vitro human megakaryocytopoiesis. PMID- 1912579 TI - Recombinant human stem cell factor, a c-kit ligand, stimulates hematopoiesis in primates. AB - Recombinant human stem cell factor (SCF) is homologous with recombinant rat SCF (rrSCF) and is a ligand for c-kit. We determined the influence of SCF on hematopoiesis in vitro and in vivo in baboons. In vitro, SCF alone stimulated little growth of hematopoietic colony-forming cells from baboon marrow, but did increase the number of colonies formed in response to erythropoietin (Epo), interleukin-3 (IL-3), and granulocyte-macrophage colony-stimulating factor (GM CSF). In vivo, SCF caused an increase in the peripheral blood of the number of erythrocytes, neutrophils, lymphocytes, monocytes, eosinophils, and basophils. In marrow, it caused an increase in marrow cellularity and in the absolute number of colony-forming unit-granulocyte-monocyte (CFU-GM) and burst-forming unit erythroid (BFU-E) in marrow following infusion of SCF. The in vivo stimulation of multiple lymphohematopoietic lineages corroborates previous in vitro studies and suggests a potentially important clinical role for SCF. PMID- 1912580 TI - In vivo production of interleukin-5, granulocyte-macrophage colony-stimulating factor, macrophages colony-stimulating factor, and interleukin-6 during intravenous administration of high-dose interleukin-2 in cancer patients. AB - Recombinant human interleukin-2 (IL-2), administered to cancer patients by continuous intravenous (IV) infusion (3 x 10(6) U/m2/d), was found to induce the in vivo production of colony-stimulating factors (CSF). Plasma obtained from patients during IL-2 treatment stimulated in vitro colony formation of normal human bone marrow cells, depleted of mononuclear phagocytes and T lymphocytes. This colony-stimulating activity (CSA) was identified as IL-5, granulocyte macrophage CSF (GM-CSF), and macrophage CSF (M-CSF), by the ability of specific antibodies against these factors to neutralize their effects. The presence of IL 2-induced GM-CSF and M-CSF was also demonstrated by specific radioimmunoassays. During IL-2 treatment, plasma also contained detectable levels of IL-6, which was measured in a bioassay. Using a cDNA-polymerase chain reaction (PCR) with specific primer sets for the various CSF, we showed that IL-2 treatment induced the expression of mRNA for M-CSF, GM-CSF, IL-3, and IL-5, but not for granulocyte CSF (G-CSF) in peripheral blood mononuclear cells, suggesting differential expression of CSF in vivo in response to IL-2. Furthermore, no negative regulators of hematopoiesis, such as interferon gamma (IFN-gamma) or tumor necrosis factor-alpha (TNF-alpha), were found in plasma. These data illustrate that in vivo administration of high-dose IL-2 may result in a stimulatory effect on hematopoiesis. The induction of detectable levels of IL-5 and GM-CSF in the circulation may explain the eosinophilia and neutrophilia observed in these patients. PMID- 1912581 TI - Involvement of a nuclear factor-kappa B-like protein in induction of the macrophage colony-stimulating factor gene by tumor necrosis factor. AB - The macrophage colony-stimulating factor (M-CSF) is required for the growth and differentiation of mononuclear phagocytes. Previous studies have demonstrated that tumor necrosis factor (TNF) induces transcription of the M-CSF gene in human myeloid cells. The present work examined the effects of TNF on cis-acting elements in the M-CSF promoter. Deleted forms of the M-CSF promoter were linked to the chloramphenicol acetyltransferase (CAT) gene and transfected by electroporation into HL-60 promyelocytic leukemia cells. The results demonstrate that an enhancer responsive to TNF stimulation is located between positions -406 and -344 upstream to the transcription start site. The fragment from positions 419 to -304 was cloned 5' to the heterologous thymidine kinase (TK) promoter and linked to the CAT gene. Both orientations of this fragment enhanced TK-promoter activity in TNF-treated HL-60 cells. The results of gel mobility shift assays with the -419 to -304 fragment demonstrate binding of a constitutive nuclear protein. A TNF-inducible protein also bound to this fragment and resulted in a different mobility pattern. Binding of the TNF-induced nuclear protein to the 419 to -304 fragment was inhibited by an oligonucleotide containing the nuclear factor-kappa B (NF-kappa B) consensus sequence. DNA footprinting demonstrated protection of an NF-kappa B binding site at positions -377 to -368. Methylation interference assays showed that the TNF-induced protein made contact points with guanine residues in the same NF-kappa B sequence. Taken together, the findings provide evidence for involvement of an NF-kappa B-like factor in transcriptional regulation of the M-CSF gene. PMID- 1912582 TI - Role of interleukin-6 in the proliferation of human multiple myeloma cell lines OCI-My 1 to 7 established from patients with advanced stage of the disease. AB - Interleukin-6 (IL-6) has been shown to stimulate the proliferation of multiple myeloma cells purified to a high degree from human bone marrow. IL-6 production in multiple myeloma has been attributed to cells belonging to the myeloma clone, thus supporting a mechanism of autostimulation. In addition, it has been shown that IL-6 may be produced by auxiliary cell populations of the bone marrow that are not part of the myeloma clone. A definitive separation of both putative sources for IL-6 may be difficult to achieve in fresh patient IL-6 growth requirement and production by pure myeloma cell populations using seven human myeloma cell lines (OCI-My 1 to 7) that were established from patients with advanced disease. The proliferative response of each line to recombinant IL-6 was measured in a clonogenic assay providing human plasma and methylcellulose as a viscous support and by 3H-thymidine uptake in liquid suspension culture. We observed marked heterogeneity, ranging from IL-6-dependent colony formation by OCI-My 4, to IL-6-independent growth. All lines expressed mRNA for the IL-6 receptor. Expression of IL-6 mRNA was analyzed after amplification by polymerase chain reaction and was present in five of seven lines. IL-6 protein was detected by enzyme-linked immunosorbent assay (ELISA) in the culture supernatants of two lines (OCI-My 3 and 2). Its functional activity was confirmed in a bioassay using the IL-6-dependent murine hybridoma line B 13.29. This activity was neutralized by anti-IL-6 antibody. Two lines did not express mRNA for IL-6. The remaining three lines expressed mRNA for IL-6, but did not secrete IL-6 protein. Immunoprecipitation experiments with lysates of one of these three lines did not detect the presence of IL-6 protein. These results suggest that autocrine stimulation by IL-6 may occur in some cell lines derived from patients with multiple myeloma. However, it does not represent a universal mechanism in myeloma cell growth. PMID- 1912583 TI - Reassignment of the human CSF1 gene to chromosome 1p13-p21. AB - Human macrophage colony-stimulating factor (CSF-1 or M-CSF) is encoded by a single gene that was previously assigned to the long arm of chromosome 5, band q33.1, in a region adjacent to the gene encoding its receptor (Pettenati MJ, et al, Proc Natl Acad Sci USA 84:2970, 1987). Using fluorescence in situ hybridization with genomic probes to examine normal metaphase chromosomes, we reassigned the human CSF1 gene to the short arm of chromosome 1, bands p13-p21. We confirmed this result by hybridizing a CSF1 cDNA probe to filters containing flow-sorted chromosomes and by identifying CSF1 sequences in DNAs extracted from human x rodent somatic cell hybrids that contained human chromosome 1 but not human chromosome 5. Our findings are consistent with studies that have shown tight linkage between the murine CSF1 and amylase genes, as part of a conserved linkage group between mouse chromosome 3 and the short arm of human chromosome 1, which also includes the genes encoding the beta subunits of thyrotropin and nerve growth factor. Assignment of the CSF1 gene to chromosome 1 at bands p13-p21 raises the possibility that it may be altered by certain nonrandom chromosomal abnormalities arising in human hematopoietic malignancies and solid tumors. PMID- 1912584 TI - Platelet storage pool deficiency associated with inherited abnormalities of the inner ear in the mouse pigment mutants muted and mocha. AB - Several inherited human syndromes have combined platelet, auditory, and/or pigment abnormalities. In the mouse the pallid pigment mutant has abnormalities of the otoliths of the inner ear together with a bleeding abnormality caused by platelet storage pool deficiency (SPD). To determine if this association is common, two other mouse pigment mutants, muted and mocha, which are known to have inner ear abnormalities, were examined for hematologic abnormalities. Both mutants had prolonged bleeding times accompanied by abnormalities of dense granules as determined by whole mount electron microscopy of platelets and by labeling platelets with mepacrine. When mutant platelets were treated with collagen, there was minimal secretion of adenosine triphosphate and aggregation was reduced. Lysosomal enzyme secretion in response to thrombin treatment was partially reduced in muted platelets and markedly reduced in mocha platelets. Similar reductions in constitutive lysosomal enzyme secretion from kidney proximal tubule cells were noted in the two mutants. These studies show that several mutations that cause pigment dilution and platelet SPD are associated with abnormalities of the inner ear. Also, these mutants, like previously described mouse pigment mutants, are models for human Hermansky-Pudlak syndrome and provide additional examples of single genes that simultaneously affect melanosomes, lysosomes, and platelet dense granules. PMID- 1912585 TI - Interleukin-4 inhibits growth of multiple myelomas by suppressing interleukin-6 expression. AB - Unfractionated bone marrow (BM) cells obtained from patients with multiple myeloma (MM) exhibit high levels of interleukin (IL)-6. Secretion of IL-6 by these cells as well as spontaneous plasma cell proliferation can be abrogated by neutralizing anti-IL-6 monoclonal antibody (MoAb). Treatment of BM cells with recombinant human (rh)IL-4 at doses of 50 to 250 U/mL blocked endogenous IL-6 synthesis in a dose-dependent fashion and was associated with significant reduction of plasma cell growth that could be reversed by exogenous rhIL-6. Enrichment of BM cells from MM patients for plasma cells and adherent cells and analysis of IL-6 mRNA in these subpopulations by means of quantitative polymerase chain reaction (PCR) showed that adherent BM cells accounted for most of the synthesis of IL-6 transcripts, whereas plasma cells displayed negligible levels of IL-6 mRNA only. These results suggest therapeutic evaluation of rhIL-4 in patients with plasma cell neoplasms. PMID- 1912586 TI - Intracellular heme coordinately modulates globin chain synthesis, transferrin receptor number, and ferritin content in differentiating Friend erythroleukemia cells. AB - The effect of succinylacetone (SA), a highly specific inhibitor of ALA dehydratase and heme synthesis, on hemoglobin (Hb) production, transferrin receptor (TfR), and ferritin expression was analyzed in differentiating Friend leukemia cells (FLC). This compound exerted a pronounced inhibitory effect not only on heme and Hb synthesis, but also on all the remaining above-mentioned parameters. In particular, SA induced: (1) a reduction of the level of alpha globin mRNA; (2) a decreased number of exposed TfR molecules, without modification of their affinity for the ligand; (3) a reduced level of TfR RNA, without significant change of TfR gene transcription rate; and (4) a lower ferritin content. The addition of exogenous hemin to differentiating FLC exerted opposite effects, and particularly induced an increase of both the number of TfRs and ferritin content. These findings suggest that in erythroid cells optimal heme synthesis is required to coordinately sustain globin chains synthesis and TfR/ferritin production; thus, the intracellular heme level may represent a key regulatory factor in the Hb synthesis pathway. PMID- 1912587 TI - The unique red cell heterogeneity of SC disease: crystal formation, dense reticulocytes, and unusual morphology. AB - Knowledge concerning SS (homozygous for the beta s gene) red blood cell (RBC) heterogeneity has been useful for understanding the pathophysiology of sickle cell anemia. No equivalent information exists for RBCs of the compound heterozygote for the beta s and beta c genes (SC) RBCs. These RBCs are known to be denser than most cells in normal blood and even most cells in SS blood (Fabry et al, J Clin Invest 70:1284, 1981). We have analyzed the characteristics of SC RBC heterogeneity and find that: (1) SC cells exhibit unusual morphologic features, particularly the tendency for membrane "folding" (multifolded, unifolded, and triangular shapes are all common); (2) SC RBCs containing crystals and some containing round hemoglobin (Hb) aggregates (billiard-ball cells) are detectable in circulating SC blood; (3) in contrast to normal reticulocytes, which are found mainly in a low-density RBC fraction, SC reticulocytes are found in the densest SC RBC fraction; and (4) both deoxygenation and replacement of extracellular Cl- by NO3- (both inhibitors of K:Cl cotransport) led to moderate depopulation of the dense fraction and a dramatic shift of the reticulocytes to lower density fractions. We conclude that the RBC heterogeneity of SC disease is very different from that of SS disease. The major contributions of properties introduced by HbC are "folded" RBCs, intracellular crystal formation in circulating SC cells, and apparently a very active K:Cl cotransporter that leads to unusually dense reticulocytes. PMID- 1912588 TI - Molecular analysis of hereditary elliptocytosis with reduced protein 4.1 in the French Northern Alps. AB - 4.1(-) hereditary elliptocytosis (HE) is a variety of elliptocytosis resulting from the reduction (heterozygosity) or the absence (homozygosity) of protein 4.1. It is nearly always encountered in its heterozygous form. It has been found among Caucasians and North Africans in a sporadic fashion. We report the study on nine family cases of 4.1(-) HE. They were recruited independently (to the exclusion of any other variety of HE) in a limited area around the city of Annecy (French Northern Alps). The mode of genetic transmission, as well as the clinical, morphologic, and protein phenotypes fully conformed to the classical description. Western blots ruled out the existence of any protein 4.1 species of abnormal size. No obvious DNA rearrangement was detectable in any of the nine families with three 4.1 cDNA probes covering the entire coding sequence and part of the flanking 5' and 3' untranslated sequences. On the basis of five polymorphic sites (Bgl II, 2; Pvu II, 3), we found five different haplotypes in normal members of the 4.1(-) families. 4.1(-) HE was associated with the most common haplotype in all the propositi. 4.1 mRNA was studied in four families. Dot-blot hybridization experiments and Northern blots failed to show any detectable change in three families. On the other hand, they showed a 2-kb deletion in the 4.1(-) messenger RNA 5'-moiety in one family. These findings emphasize the heterogeneity of 4.1(-) HE at the molecular level. PMID- 1912589 TI - T-cell depletion of HLA-identical transplants in leukemia. AB - We analyzed the effects of T-cell depletion on the outcome of HLA-identical sibling bone marrow transplants for leukemia by comparing 731 T-cell-depleted transplants with 2,480 non-T-cell-depleted transplants. T-cell depletion decreased acute graft-versus-host disease (GVHD) (relative risk [RR] 0.45; P less than .0001) and chronic (GVHD) (RR 0.56; P less than .0001). However, it increased graft failure (RR 9.29; P less than .0001). Leukemia relapse also was increased. In first remission acute leukemia or chronic phase chronic myelogenous leukemia, leukemia relapse was 2.75 times more likely after T-cell-depleted transplants (P less than .0001). T-cell depletion increased the risk of treatment failure (RR 1.35; P less than .0003) and decreased leukemia-free survival. We also studied controllable variables associated with outcome of T-cell-depleted transplants. The unique findings were that among recipients of T-cell-depleted transplants for early leukemia, radiation doses greater than or equal to 11 Gy (RR 0.54; P less than .01), dose rates greater than 14 cGy/min (RR 0.56; P less than .002), and additional posttransplant immune suppression with cyclosporine alone (RR 0.53; P less than .0006) or cyclosporine plus methotrexate (RR 0.36; P less than .01) were associated with fewer treatment failures. Use of monoclonal antibodies rather than physical techniques for T-cell depletion (RR 2.01; P less than .03) and fractionated radiation (RR 1.69; P less than .05) were associated with increased treatment failure and lower leukemia-free survival. These data may be useful in designing strategies to improve results of T-cell-depleted transplants. PMID- 1912590 TI - Late failure of autologous marrow grafts in lethally irradiated dogs given anti class II monoclonal antibody. AB - We established a model of canine marrow autografts after 9.2 Gy total body irradiation (TBI) to study the role of class II antigens in hematopoietic stem cell growth and differentiation. Twenty dogs were given 9.2 Gy TBI, marrow, and intravenous (IV) murine anti-class II monoclonal antibody (MoAb). Infusion of 0.6 mg/kg/d of MoAb H81.98.21, an IgG2a reactive with HLA-DR, on days 0 to 4 after TBI did not prevent initial engraftment, but dogs died with late graft failure. MoAb B1F6, an IgG2a reactive with HLA-DR + DP, had no adverse effect on engraftment, although both MoAbs detect antigens on stem cells. The critical time for the effect of MoAbs is the first 4 days after transplantation. Our findings argue against several pathogenetic mechanisms, including removal of MoAb-coated stem cells by the reticuloendothelial system (RES), canine complement-mediated cytotoxic effects on stem cells, antibody-dependent cellular cytotoxicity, and inactivation of MoAb-coated cells by dog anti-mouse antibody. To distinguish between MoAb-induced damage to microenvironment (ME)/accessory cells (AC) and late graft failure from a lack of pluripotent stem cells, three dogs were given TBI, a marrow autograft, and MoAb H81.98.21 on days 0 to 4; one, given thoracic duct cells on day 6, developed graft failure; the other two, given marrow depleted of AC by L-leucyl L-leucine o-methyl ester (Leu-Leu-OMe), had sustained grafts. Findings support the notion that originally transplanted pluripotent stem cells are no longer present on day 6 and that the ME is functional and able to support newly injected stem cells. PMID- 1912591 TI - Detection of human monocyte-reactive alloantibodies by flow cytometry after selective downmodulation of the Fc receptor I. AB - Monocyte-reactive human alloantibodies may be of importance in situations such as transfusion reactions and bone marrow and kidney transplantation. So far, only complement-binding monocyte-reactive antibodies can be detected with a cytotoxicity assay. No antiglobulin assays are yet available that also detect noncomplement-fixing monocyte-reactive antibodies. The binding of monomeric IgG with high affinity to the Fc receptor I (FcRI) on monocytes has severely hampered the development of such an assay until now. We report on the selective removal of the FcRI from monocytes to test human sera in a flow cytofluorometry assay for the presence of monocyte-reactive IgG alloantibodies. Selective downmodulation of FcRI was accomplished by incubating the cells with murine monoclonal antibodies against FcRI followed by a second incubation with goat-antimouse IgG polyclonal antibodies. With such modified cells, human complement-binding and noncomplement binding IgG and IgM alloantibodies against polymorphic determinants of the HLA class I and II glycoproteins, the human monocyte antigen system and polymorphic antigenic determinants of the LFA complex, can be detected in a sensitive and reproducible manner. PMID- 1912592 TI - Anti-D Ig for treatment of immune thrombocytopenic purpura. PMID- 1912593 TI - Mechanism of iron uptake. PMID- 1912594 TI - Frontiers on bone marrow transplantation: fetal hematopoiesis. PMID- 1912595 TI - Frontiers in bone marrow transplantation. AB - The early murine experiments and human studies that indicated the potential of marrow transplantation are reviewed. The results of marrow grafting for a variety of human diseases are summarized. Current directions of research are indicated. PMID- 1912596 TI - Embryonic and fetal hemopoiesis: an overview. AB - Our current knowledge of embryonic and fetal hemopoiesis is critically reviewed in this article. In both murine and human systems, embryonic and fetal development is associated with multiple switching in the sites of hemopoiesis. The phenomenon is first extraembryonic, occurring in blood islands of the yolk sac. Hemopoietic stem cells (HSC) appear to derive from hemangioblasts that are of mesodermal origin. Yolk sac milieu is permissive only for erythropoiesis which proceeds synchronously and may be erythropoietin-insensitive. Yolk sac milieu is not permissive for the development of other cell lines. The final product is nucleated red cells. Yolk sac hemopoiesis is an example par excellence of primitive (as compared to definitive) form of hemopoiesis. HSC then seem to migrate via the bloodstream to the liver and spleen to seed these tissues, which then carry the burden of hemopoiesis until birth and for some time thereafter. Here also erythropoiesis predominates, but some granulopoiesis also occurs. Thus, the milieu is not totally impermissive. Hemopoiesis is in definitive form, lacking synchronicity of cell growth with the end product being anucleated cells and synthesized hemoglobin not limited to embryonic type. The site of hemopoiesis is finally transferred to the bone marrow, which is predominantly granulopoietic. Certain cellular and embryological features of these types of hemopoiesis in the context of more recent molecular understanding of stem cell homing are discussed. PMID- 1912597 TI - Self-renewal and migration of stem cells during embryonic and fetal hematopoiesis: important, but poorly understood events. PMID- 1912599 TI - Effects of insulin-like growth factors on hemopoiesis. PMID- 1912598 TI - Induction of circulating neonatal stem cell populations. AB - Hematopoietic cell differentiation and growth are regulated by paracrine molecules that include insulin and insulin-like growth factors (IGFs). IGF-I and II stimulation of erythropoiesis in cultures of adult bone marrow and peripheral blood cells and murine fetal liver cells has been previously reported. In order to investigate whether these paracrines also influence differentiation and proliferation of human neonatal progenitor cells, we assessed their effects in cultures of umbilical cord blood and adult blood and marrow cells, using a serum substituted system. IGF-I stimulated colony-forming unit-erythroid (CFU-E) derived colony formation by adult cells by up to 265%, while IGF-II augmented colony formation by up to 100% in the presence of erythropoietin. Stimulation occurred in a saturable fashion over concentrations of 0 to 200 ng/ml. Similar results were obtained in subcultures of adult-circulating progenitors. Moreover, a subpopulation of erythropoietin-independent adult CFU-E was stimulated to proliferate by IGF-I but not by IGF-II. In contrast to these effects in adult marrow culture, IGF-II exerted a greater stimulatory effect on neonatal CFU-E proliferation than did IGF-I in erythropoietin-containing cultures. Additionally, IGF-II stimulated proliferation of erythropoietin-independent neonatal CFU-Es in a concentration-dependent fashion. Together, the data are consistent with the hypothesis that somatomedins are involved in developmental regulation of erythropoiesis. PMID- 1912600 TI - Directions in gene therapy. AB - Retroviral mediated gene transfer has proven to be an effective method of transferring genetic material into many different mammalian cells. Presented in this short review is a history of retroviral-mediated gene transfer as it relates to hematopoietic- and blood-derived cells. Gene transfer into mouse, primate, and fetal sheep and primate hematopoietic stem cells is discussed. Gene transfer into lymphocytes, in particular tumor-infiltrating lymphocytes, is also addressed. The use of such lymphocytes in ongoing and submitted clinical protocols utilizing retroviral-mediated gene transfer are presented. PMID- 1912601 TI - Human gene therapy: the future is now, the promise yet to come. PMID- 1912602 TI - L-arginine does not restore endothelial dysfunction in atherosclerotic rabbit aorta in vitro. AB - Bioassay studies suggest that impaired endothelium-dependent relaxation in atherosclerotic arteries is due to a reduced release of biologically active endothelium-derived relaxing factor (EDRF). We tested the hypothesis that endothelial dysfunction is caused by deficiency of the EDRF precursor L-arginine. Aortae from normal and cholesterol-fed (1%, 4 months) rabbits were excised and incubated for 1 h with 5 mM L-arginine. Pretreatment with L-arginine had no effect on the relaxation to acetylcholine in normal vessels and was without effect on the impaired response of atherosclerotic arteries to acetylcholine. This finding suggests that L-arginine deficiency is unlikely the underlying cause of impaired endothelium-dependent relaxation in the aorta of cholesterol-fed rabbits. PMID- 1912603 TI - Effect of age on rabbit aortic responses to relaxant endothelium-dependent and endothelium-independent agents. AB - The aim of this study was to evaluate the effects of aging on endothelium dependent and endothelium-independent relaxation of rabbit thoracic aorta from New Zealand white rabbits aged 4-6 and 7-12 months. The contractile response to noradrenaline (NA) decreased with increasing age, but NA [EC50] did not vary significantly. Acetylcholine (Ach)-induced relaxation of aortic rings precontracted with NA [EC50] did not change significantly with increasing age. The relaxation induced by ATP of aortic rings, precontracted with NA [EC50], was significantly greater in young than in adult rabbits. This difference between young and adult animals became more evident in aortic rings deprived of endothelium: in adult animals, the ATP-induced relaxation of aortic rings with endothelium was significantly greater than in the rings without endothelium. The endothelium-independent relaxation by sodium nitrite (NaNO2) at lower concentrations was significantly greater in young than in adult rabbit aortic rings precontracted with NA [EC50]. Concluding, the age-induced changes in vascular response in male New Zealand white rabbits are related to an impaired mechanism at smooth muscle level. PMID- 1912604 TI - Growth responses in isolated elastic, muscular and resistance-sized arterial segments of the rat. AB - To evaluate whether intravascular phenomena contribute to local differences in growth responses of the arterial wall, we evaluated responses to organoid culture in a broad variety of arterial preparations. Arterial segments were isolated from adult, normotensive rats, sympathectomized, denuded from endothelium, and suspended in medium supplemented with serum. As judged from the nuclear incorporation of the thymidine analogue 5-bromo-2'-deoxyuridine (BrdUrd), this induced a transient stimulation of DNA synthesis in only a fraction of the arterial smooth muscle cells in all types of arteries. This intramedial DNA synthesis was more marked in renal arteries than in carotid arteries or aortae and was least pronounced in main pulmonary, femoral, and superior mesenteric artery and in mesenteric resistance-sized arteries. Organoid culture of isolated arteries did not increase the cross-sectional area of the media or the number of medial cells. It rather resulted in proliferation of smooth-muscle-like cells outside the media. In addition, smooth-muscle-like cells migrated out of the isolated arterial segments during culture. The rate of proliferation of these isolated cells did not differ between large arteries of different anatomical origin. However, isolated cells derived from mesenteric resistance arteries proliferated at a rate that was 4 times slower than that of large artery cells. The presence of endothelium significantly reduced medial DNA synthesis in carotid and renal artery segments, but not in mesenteric resistance-sized preparations. These data indicate that growth responses of the arterial wall differ quantitatively with the anatomical location and branching order of the vascular segment. In addition to the regional heterogeneity of endothelial effects on mitogenic responses of arterial smooth muscle, this seems to be due to regional differences in the susceptibility of arterial smooth muscle to exogenous growth factors. In this respect, we speculate that subsets of growth-resistant and growth-prone arterial smooth muscle cells could be heterogeneously distributed over the arterial tree. PMID- 1912605 TI - Quantitative measurement of fixation rate and dimension changes in the aldehyde/pressure-fixed canine carotid artery. AB - Excised canine carotid arteries held at constant physiologic length were cycled from -13 to +27 kPa with a constant-flow infusion pump, and the pressure-volume curves were recorded. The change in diameter on reducing the pressure from 16 to 0 kPa was determined and the strain of recoil [(diameter16- diameter0)/diameter16] calculated. Diameter recoil was reduced from 51% (fresh tissue) to 5% after 3 h pressure fixation in 4% formaldehyde and to 9% after 15 min in 2% glutaraldehyde with little further change. Lengthwise recoil was reduced from 37 to 10% after 5 min in 2% glutaraldehyde. Photographs were taken to measure outer diameter during pressure fixation. There was no change in diameter in either fixative from the first minute up to 3 days at the constant pressure of 16 kPa. PMID- 1912606 TI - Endothelial cell morphology around graded stenoses of the dog common carotid artery. AB - Graded stenoses (40-64% diameter reduction) were applied to dog common carotid arteries under anesthesia, and 27 days later the poststenotic velocity field was examined using transcutaneous pulsed Doppler velocimetry. Following in situ fixation, endothelial cell area, shape and orientation was measured by digitizing endothelial cell outlines in scanning electron micrographs. Endothelial cell area in the vicinity of the stenosis throat (within +/- 1 diameter) was reduced. No relation to stenosis hemodynamics was apparent. Cell area was increased 5 diameters downstream; in this region, there was turbulence due to jet break up. Cells were maximally rounded at the stenosis throat and gradually returned to upstream elongation by 5 diameters downstream. There was a region of flow separation and low velocity recirculation between the stenosis and the site of maximum turbulence, thus, downstream cell rounding was associated with flow separation. Subdivision of the experiments into four stenosis grades revealed little variation of the pattern of morphology between groups. It is possible that this is related to flow limitation with increasing grade. Elongation of endothelial cells through the entrance of the stenosis was apparent in only four experiments. Poststenotic dilatation of greater than 12% external diameter increase was noted in only four out of the sixteen experiments. In general, the relation of cell elongation to shear stress is supported, but this relationship does not fully explain endothelial cell shape at a stenosis. PMID- 1912607 TI - Nitric oxidergic neurogenic vasodilation in the porcine basilar artery. PMID- 1912608 TI - Breast deformity, its correction, and assessment of breast conserving surgery. AB - A combination of quadrantectomy, axillary dissection, and radiotherapy (QUART) is the regimen most favored by Japanese surgeons among a variety of breast conserving therapies currently available against breast cancer. Unfortunately, extensive resections such as quadrantectomy often give poor local cosmetic results in patients with small breasts. With the aim of improving the cosmetic aspect after an extensive resection, immediate transposition of the latissimus dorsi muscle (LDM) was carried out in breast conserving surgery. To date, twenty one patients have been entered in this study. Post-quadrantectomy breast deformity was not corrected in six patients including one with bilateral breast cancers, but was corrected by transposition of a part of LDM in 14 other patients. In the last patient, who also had bilateral breast cancers, the right breast was treated by QUART and the left breast by subcutaneous mastectomy followed by transposition of LDM. The cosmetic outcome for these patients was assessed both subjectively and objectively; the objective assessment used a Moire topography camera. The postoperative appearance and topography revealed a satisfactory symmetry of breasts in the transposed patients, especially those with small breasts, when compared with non-transposed patients. It may be concluded that the transposition of LDM is useful in preventing breast deformity following an extensive resection in breast conserving surgery. PMID- 1912609 TI - 13th San Antonio Breast Cancer Symposium--Plenary Lecture. Steroid hormone receptors as transactivators of gene expression. AB - In the two decades since the discovery of the steroid hormone receptors, a great deal has been learned about their structure, their relationships with each other, and the target sequences (response elements) at which they regulate expression of specific genes. Analysis of receptor sequences has confirmed the existence of several domains with distinct functions in each receptor molecule, and has also indicated that the steroid receptors are members of a 'superfamily' which also includes receptors for vitamin D, retinoic acid, thyroid hormone and its related oncogene v-erbA, and a substantial number of 'receptors' whose ligands are still unidentified. The response element sequences are also closely related, and we are beginning to understand the interaction of the receptors with these response elements and with proteins bound nearby such as transcription factors. Certain naturally occurring genetic diseases have been identified with specific receptor mutations. The future promises greater understanding not only of the detailed action of the receptors of this superfamily, but of their precise role in fertility, development, and disease. PMID- 1912610 TI - Multiple growth factor independence in rat mammary carcinoma cells. AB - In previous studies we demonstrated that rat mammary tumor (RMT) cells that are serially transplantable consist of cells that are independent of growth factors strictly required by normal rat mammary epithelial (RME) cells for growth in serum-free culture. The present studies were designed to determine the extent of the growth factor independence of several cell lines derived from these tumors and to determine if the cells that expressed growth factor independence in vitro are also tumorigenic in vivo. Cells from a transplantable mammary carcinoma (8-12 RMT) were seeded into culture in serum-free medium in the absence of either insulin (IN), epidermal growth factor (EGF), or cholera toxin (CT), and cell populations independent of the individual factors were developed. Next, the three growth factor independent populations were tested for their ability to grow in the absence of multiple growth factors. 8-12 RMT cells did not lose proliferative potential when multiple growth factors were deleted from the medium. Indeed, 8-12 RMT cells could be serially propagated in serum-free medium supplemented solely with bovine serum albumin (BSA) and ethanolamine. Cell lines independent of single growth factors were also developed from two other transplantable tumors (1 9 RMT and 7-15 RMT). In contrast to the 8-12 RMT-derived cell lines, deletion of additional growth factors from the media of the 1-9 RMT and 7-15 RMT-derived cells resulted in dramatic losses in growth potential. These results suggest that independence of individual growth factors is mediated by different mechanisms, since cells from different tumors can stably express independence of one, two, or three or more factors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1912611 TI - Polyamine involvement in the secretion and action of TGF-alpha in hormone sensitive human breast cancer cells in culture. AB - These experiments were designed to test polyamine (PA) involvement in the secretion and action of transforming growth factor alpha (TGF-alpha) in hormone responsive MCF-7 breast cancer cells in liquid culture. At the same time, we evaluated the influence of culture conditions (with serum vs. serum depleted) and subclonality of MCF-7 cells on PA involvement in estrogen (E2) and TGF-alpha stimulated cell proliferation. Despite inducing a profound suppression of cellular PA levels and inhibiting basal and E2-stimulated growth, administration of the PA synthesis inhibitor alpha-difluoromethylornithine (DFMO) did not influence either basal or E2-induced TGF-alpha secretion. In the same experiments, on the other hand, addition of DFMO completely blocked the growth stimulatory effect of exogenous TGF-alpha. However, when the culture conditions were changed to serum-free medium, TGF-alpha and E2-induced cell proliferation was affected modestly or not at all by DFMO administration, despite similar suppression of cellular ornithine decarboxylase (ODC) activity and PA levels. In addition, different clones of MCF-7 cells differed in their sensitivity to the antiproliferative effect of DFMO as well as in basal levels of ODC activity and PA. We conclude that PAs are not involved in basal or E2-stimulated TGF-alpha secretion in MCF-7 breast cancer cells. On the other hand, PAs do seem to be important mediators of TGF-alpha and E2-induced breast cancer cell proliferation, though the degree of such involvement appears to be influenced by serum factors and clonal variability of MCF-7 cells. PMID- 1912612 TI - Estrone sulfatase activity and effect of antiestrogens on transformation of estrone sulfate in hormone-dependent vs. independent human breast cancer cell lines. AB - The effect of the anti-estrogens ICI 164,384 and tamoxifen on the estradiol (E2) concentration after incubation of estrone sulfate (E1-S) with different hormone dependent (MCF-7 and T-47D) and hormone-independent (MDA-MD-231 and MDA-MB-436) mammary cancer cells, as well as the estrone sulfatase activity in these various cell lines, are presented. The anti-estrogen ICI 164,384 decreased very significantly the concentration of E2 after incubation of E1-S with MCF-7 (control, mean +/- SE: 100 +/- 24 pg/mg DNA; + ICI 164,384 [10(-6)M]: 7 +/- 2 pg/mg DNA). This effect was much more intense than with tamoxifen. A similar effect was observed with T-47D cells. However, no significant effect was observed in the hormone-independent cells. In the intact cell, estrone sulfatase activity was very intense in the hormone-dependent cells, but very small in the hormone independent cells. However, this activity became very strong after homogenization in the hormone-independent cells. The data suggest that estrone sulfate can play an important role on the bioavailability of E2 in hormone-dependent breast cancer, and that understanding the control of estrone sulfatase activity can open new knowledge of the estrogen responses and new possibilities of therapeutic application in breast cancer. PMID- 1912614 TI - Clinical indicators: development and use. PMID- 1912613 TI - C-13 NMR spectroscopy of plasma reduces interference of hypertriglyceridemia in the H-1 NMR detection of malignancy. Application in patients with breast lesions. AB - We have previously described the application of water-suppressed proton nuclear magnetic resonance (H-1 NMR) spectroscopy of plasma for detection of malignancy. Subsequently, hypertriglyceridemia has been identified as a source of false positive results. We now describe a confirmatory, adjunctive technique--analysis of the carbon-13 (C-13) NMR spectrum of plasma--which also identifies the presence of malignancy but is not sensitive to the plasma triglyceride level. Blinded plasma samples from 480 normal donors and 208 patients scheduled for breast biopsy were analyzed by water-suppressed H-1 and C-13 NMR spectroscopy. Triglyceride levels were also measured. Among the normal donors, there were 38 individuals with hypertriglyceridemia of whom 18 had results consistent with malignancy by H-1 NMR spectroscopy. However, the C-13 technique reduced the apparent H-1 false positive rate from 7.0% to 0.6%. Similarly, in the breast biopsy cohort, C-13 reduced the false positive rate from 2.8% to 0.9%. Furthermore, the accuracy of the combined H-1/C-13 test in this blinded study was greater than 96% in 208 patients studied. PMID- 1912615 TI - Development and application of clinical indicators for nursing. PMID- 1912616 TI - Major clinical functions: a unifying framework for measuring outcomes. PMID- 1912617 TI - Patient falls: an outcome indicator. PMID- 1912618 TI - An assessment tool for developing quality indicators. PMID- 1912619 TI - Clinical indicators: a tool for improving pain management documentation. PMID- 1912620 TI - Developing nursing-focused quality indicators: a professional challenge. PMID- 1912621 TI - Noise in critical care units: a quality assurance approach. PMID- 1912622 TI - Description of indicator development for a percutaneous transluminal coronary angioplasty monitor. PMID- 1912623 TI - Decision analysis: a method to improve quality of care for nursing practice. PMID- 1912624 TI - Changing nursing practice to prevent elopement. PMID- 1912625 TI - QA productivity. PMID- 1912626 TI - The use of dental implants in comprehensive therapy. AB - The replacement of missing teeth in partially or fully edentulous patients conventionally involved fixed or removable, partial or full prostheses supported by either natural teeth, soft tissues, or both. Prosthetic reconstructions were often limited by the number or distribution of abutment teeth, the morphology of the alveolar ridges, the periodontal health, or the remaining hard tissue structures of the abutment teeth. The possibility of adding abutments by inserting oral implants has, therefore, been a treatment approach desired for a long time by practitioners. However, it was not until recently that sufficient long-term success rates with implants could be reported. This review is limited to the new generation of implants that heal by osseointegration. PMID- 1912627 TI - Supportive periodontal treatment: maintenance. AB - An increasing emphasis is being placed on the phase following active therapy for inflammatory periodontal diseases. This phase of therapy, once termed maintenance, is now called supportive periodontal therapy (SPT) (American Academy of Periodontology, Current Procedural Terminology for Periodontics. 5th American Academy of Periodontology, 1986). Supportive periodontal therapy has been shown to have an important role in controlling periodontal problems. However, most patients do not comply with suggested SPT intervals. PMID- 1912628 TI - Epidemiology of periodontal disease. AB - The year covered in this review was marked with significant reports related to the prevalence and severity of periodontal disease in the United States and throughout the world. A series of well-conducted studies reported in peer reviewed journals examined risk factors related to the high severity of periodontal disease as measured by progressive attachment loss. An interesting development during the year is the increased attention paid to collaborative international studies that document periodontal disease prevalence and severity in six different countries, thus providing a broader understanding of periodontal disease on a worldwide basis. Importantly, several papers discuss the policy implications of the periodontal literature for educational programs and clinical practice. These papers include major reports on national treatment needs in the United States, the use of statistical models and problems related to statistical analysis of periodontal data, and finally, a call for the use of epidemiologic data in program planning, implementation, and evaluation. PMID- 1912629 TI - Etiology of periodontal diseases. AB - Periodontal diseases are a series of complex, distinct, pathologic entities caused by the interaction of bacterial plaque and the host. This interaction results in destruction of the supporting alveolar bone and connective tissue. Although bacterial plaque has been implicated as the primary etiologic agent in most forms of periodontal disease, there are local and systemic factors which may modify both microbial and host components. Local factors may favor plaque accumulation and maturation, while systemic factors may modulate and decrease the host's protective response. PMID- 1912630 TI - Host responses in the etiology and pathogenesis of periodontal disease. AB - Periodontal disease is an inflammatory condition of the supporting structures of teeth. This condition is actually considered to be caused by a number of different diseases, possibly associated with different etiologies, rather than a single disease. Due to limitations in our present understanding of cellular and molecular events involved in the pathogenesis of various periodontal diseases, many therapeutic failures still occur. For this reason, studies concerning the responses of the host to pathogenic bacteria are thought to be critically important. This review presents current opinions on the role of host responses in periodontal disease. PMID- 1912631 TI - Bacteriologic monitoring of periodontal diseases: cultural, enzymatic, immunologic, and nucleic acid studies. AB - Evidence supporting the bacteriologic etiology of periodontal diseases has led investigators to monitor the microbiologic species associated with each disease. The type of study performed has evolved at different levels over the years and is predominantly influenced by available technologies. As the technology has advanced, so too have attempts at monitoring specific microorganisms. The ultimate goal in most research efforts on clinical bacteriologic monitoring of the periodontal diseases has been to obtain a method of measuring microorganisms in a specific, rapid, low-cost fashion. The method would be used on a daily basis at chairside in the dental operatory to direct treatment at a target microbial population, evaluate treatment, or predict future areas of attachment loss. It is suggested that future efforts try to incorporate microbiologic-host interactions that are likely to be important in the etiology and pathogenesis of the periodontal diseases. PMID- 1912632 TI - The normal and diseased periodontium and periodontal disease activity. AB - Scientific knowledge regarding the cellular and molecular biology of the periodontium in health is fundamental to the determination of how periodontal diseases begin and progress. Advances in diagnosis and treatment are in turn becoming increasingly dependent upon advances in the molecular biology of inflammation-induced changes in the periodontal tissues, and the regenerative capacity of the periodontal cells. New in vitro cell culture models, a broadening array of monoclonal antibody reagents, and general advances in scientific methodology have presented the field of periodontal research with excellent opportunities to explore the mechanisms of tissue destruction, as well as test innovative means to induce tissue regeneration. Laboratory and clinical findings in the past year have led to major expansions in how we perceive the pathogenesis of periodontal diseases, and also have altered our long-held beliefs about periodontal disease activity. PMID- 1912633 TI - A comparison of probing and radiographic methods for detection of periodontal disease progression. AB - Over the last decade new technology has increasingly been applied to periodontal probing and radiography to result in diagnostic methods with greater resolution, repeatability, and accuracy. The goal of this paper is to discuss these methods with special emphasis on data published within the past year. Moreover, this paper summarizes the state of our current understanding of the usefulness of these methods in patient care and research. PMID- 1912634 TI - Crevicular fluid-based diagnostic tests. AB - A diagnostic test seeks to establish the presence or absence of a disease. Many tests also seek to determine the severity, progression, or level of activity of a disease as well as the disease's likely further progression. Crevicular fluid based diagnostic tests for various periodontal diseases are currently attracting much interest in clinical, academic, and industrial circles. This is because existing clinical diagnostic tests have many shortcomings. By the use of these techniques it is hoped that treatment will become more effective, and that overtreatment will be avoided, thus resulting in a more cost-effective outcome. Much basic work relevant to the development of such tests is underway, covering a wide range of potential analytes, and the contributions to the referred literature in all of these areas in the past year are reviewed. PMID- 1912635 TI - General considerations in the treatment of periodontal disease: infection control, medications, and wound healing. AB - Although it is difficult to accurately predict the results of periodontal therapy, it may be possible to improve the success of therapy if the patient is considered from an immunologic, microbiologic, social, and behavioral point of view, as a heterogenous entity. The success or failure of a particular treatment can be related to the host's personal response to a therapeutic procedure rather than to the technique used. PMID- 1912636 TI - Scaling and root planing: removal of calculus and subgingival organisms. AB - Scaling and root planing studies have shown that despite the best efforts of skilled clinicians, it is almost impossible to achieve calculus-free roots. Flap access nearly doubles the operator's ability to remove calculus. Furcation areas, however, continue to harbor significant amounts of calculus after scaling and root planing with or without the benefit of a flap. While thorough root debridement and planing are desirable treatment goals, not all would agree that complete cementum removal is either possible or desirable, or that the removal of calculus is more important than plaque or endotoxin removal in achieving clinical success. PMID- 1912637 TI - Chemotherapeutic agents as adjuncts in the treatment of periodontal disease. AB - Periodontal disease is a broad term designating a number of infectious disease entities involving the supportive tooth structures. It has become clear that the various forms of periodontal disease are associated with specific groups of microorganisms. This evidence has led to treatment strategies that are primarily aimed at the suppression or elimination of specific periodontal pathogens. Until recently, surgical and mechanical intervention remained the principal methods for control of the multifactorial disease process. Recent advances in the development of chemotherapeutic agents have led to the increasing use of antimicrobials to suppress pathogenic flora. The use of antimetabolic agents to modulate host inflammatory response to the accumulation of bacterial plaque has also increased. Both types of chemotherapeutic agents can be used alone or in conjunction with traditional periodontal therapy to provide effective and predictable clinical improvement. PMID- 1912638 TI - Surgical treatment of periodontal diseases: access flaps, bone resection techniques, root preparation, and flap closure. AB - Surgical periodontal therapy has been used for decades in an attempt to halt the progression of chronic, adult periodontitis. Numerous surgical techniques have been proposed, each generally aimed at mechanical debridement of the periodontal lesion and associated root surface, facilitation of healing, and creating an environment capable of being stabilized by a normal periodontal maintenance routine. Certain surgical approaches provide better access for debridement or assure flap repositioning at a level which results in an optimal anatomic relationship between soft tissue and teeth following healing. PMID- 1912639 TI - Soft-tissue plastic surgery. AB - Soft-tissue plastic surgery was previously referred to as mucogingival surgery by Friedman (Tex Dent J 1957, 75:358-362). This term referred to any surgery "designated to preserve attached gingiva, to remove frena or muscle attachment, and to increase the depth of the vestibule." The aim of this type of surgery was to maintain an adequate mucogingival complex, focusing on the importance of the amount of attached gingiva. Soft tissue plastic surgery is important not only for reasons of health, but also for cosmetic purposes. PMID- 1912640 TI - Systems for use in critical care. PMID- 1912641 TI - Unit in review Royal Perth Hospital--ICU--25 years of progress. PMID- 1912642 TI - Confederation of Australian Critical Care Nurses. "Why is it so important to be one organisation". PMID- 1912643 TI - Do intensive care nurses consider intensive care less useful than their patients or patient's family? AB - Do Intensive Care Nurses feel that Intensive Care (IC) treatment is worthwhile for their patients? Can they speak for their patients, when considering how useful IC would be, in the event of life-threatening illness? And, do quality of life (QOL) considerations affect IC nurses', and patients', and patients' family perceptions of the usefulness of IC treatment? To determine how useful they perceived IC treatment to be 44 ex-patients (or their family if the patient had died) were asked how willing they would be to return to IC (or have their relative return to IC) if again threatened by critical illness. 16 Registered Nurses (RNs) were asked how useful they considered IC would be for patients they had nursed, if those patients' treatment in IC could be done all over again. RNs were also asked how useful they considered IC to be if they themselves required it. Patient (or family) responses were matched with the corresponding RN responses and compared (39 matched pairs). The comparison showed, 1--Patients and families did not consider QOL effected their judgement of the usefulness of IC; 2 -Patients and families considered IC useful for all periods of survival; 3--RNs considered IC much less useful than patients and families; 4--QOL was a significant consideration for RNs when assessing the usefulness of IC for their patients. These results have implications for RNs who attempt to represent the patients' view when assessing the usefulness of IC. PMID- 1912644 TI - Intensive care of the crush victim. Part 1. AB - The victims of disasters, accidents and many forms of trauma are often trapped or wedged under and within rubble which can lead to crush injury. Prolonged immobility can also cause crush injury if the weight of a person's body compresses muscle and soft tissue for an extended period of time. Extensive muscular tissue pathology can result from the crush injury itself and once the pressure, or compressive force, is removed a predictable sequence of events can cause widespread haemodynamic and metabolic disturbances--the crush syndrome. Part one includes the mechanism of crush injury and the pathophysiology underlying the clinical manifestations of the crush syndrome. The aims of assessment and management are discussed as well as a brief review of the literature related to management of the local crush site and the potential problem of compartment syndrome. Part two involves a case study of a person who was trapped for 10-12 hours following a motor vehicle accident. This patient was transported to 2 country centres and then transferred to a major teaching hospital in Sydney. Discussions will centre on the classic nature of the case, and the findings and management strategies will be correlated with the literature. The implications for nursing practice are explored and include the need for astute assessment and monitoring based on a thorough understanding of the sequelae of crush. Interventions are aimed at minimising discomfort and reducing complications both at the local crush site and generalised systemic level. Close monitoring and interpretation of the patient's response to interventions is essential for the continuation of definitive care. PMID- 1912645 TI - Nursing research targets into the twenty first century. First draft policy statement--June, 1991. PMID- 1912646 TI - Article review process. PMID- 1912647 TI - History of the development of the Confederation of Australian Critical Care Nurses. PMID- 1912648 TI - Continuing education--within the intensive care unit. An essential requirement for promoting expert practice and reducing perceived staff stress. AB - This paper describes research designed to explore the relationship between perceived staff stress and continuing education needs for varying categories of registered nurses. A self rating instrument was used, a pilot study conducted and then data collected from registered nurses (n = 49) working in a general ICU. The data was analysed and compared in relation to perceived practice level, critical care nursing qualifications and time worked in ICU. The results demonstrated differences between those staff with critical care certificates and those without in relation to contributing factors to unpleasant stress, focus of continuing education sessions and involvement in continuing education. PMID- 1912649 TI - Asserting our role in decision making. PMID- 1912650 TI - Intensive care of the crush victim. Part II. AB - In Part I of this paper, "Intensive care of the Crush victim" (1) Gayle Burr presented the mechanism of crush injury and the pathophysiology underlying the clinical manifestations of the crush syndrome, its assessment and management. Part II outlines the case study of John who was trapped for 10-12 hours following a motor vehicle accident. A chronological overview of the events in this case will be described. The medical management and nursing implications of each of his presenting complications will be discussed. PMID- 1912651 TI - Normal and disordered swallowing: new insights. AB - Swallowing is a complex sequence of integrated motor events which is programmed entirely within a 'pattern generator', the medullary swallow centre. The swallow is not a reflex but rather a programmed response which is only initiated given the right combination of cortical and peripheral sensory cues to the medulla. Interruption of these afferent pathways profoundly influences the ability to initiate a swallow. While the basic sequence of motor events that constitutes a swallow is constant, the temporal relationships among component events are modifiable according to the characteristics of the swallowed bolus. The pathophysiology of dysphagia can be categorized on the basis of dysfunction of one or more of seven broad mechanisms that make up the swallow: bolus preparation, lubrication, oral delivery, palatal closure, airway closure, pharyngeal propulsion and UOS opening. This mechanistic approach originates directly from the videoradiographic observations and provides a rational basis for treatment. Videoradiography is the single most valuable technique in the evaluation of oral pharyngeal dysphagia. Oesophagoscopy and laryngoscopy should be performed in most cases because small tumours in the region can mimic pharyngeal motor disorders and may be easily overlooked. Manometry is providing valuable physiological and pathophysiological information about swallowing but, as an adjunct to videoradiography, only provides additional important information in the minority of patients undergoing investigation. PMID- 1912652 TI - Approaches to management of disordered swallowing. AB - Management of disordered oropharyngeal swallowing begins with careful assessment of the patient's oropharyngeal anatomy and physiology, medical status and cognitive, language and behavioural characteristics. More often, videofluoroscopic studies are performed which enable observation of bolus movement and movements of the oral cavity, pharynx and larynx throughout the swallow. Treatment for oropharyngeal dysphagia may take the form of compensatory strategies, direct therapy or indirect therapy. Compensatory strategies include postural changes and modification of bolus volume and consistency as well as rate of food presentation. These strategies are designed to eliminate the symptoms of the swallowing problem but may not directly change swallow physiology. Direct therapy techniques are designed to change swallow physiology and consist of oral sensory stimulation techniques and swallow manoeuvres, as well as maxillofacial prosthetics, medication and surgical procedures. Indirect therapy procedures are designed to improve the neuromuscular controls necessary for the swallow without actually producing a swallow. Specific swallowing treatment strategies within each category are described. In addition to assessing the patient's swallow physiology, the videofluoroscopic study of the swallow can be used as a treatment efficacy trial in which selected compensatory strategies or direct therapy techniques are used by the patient to improve their swallow safety and efficiency. Factors to be considered in the design of an overall treatment plan for a patient with disordered swallowing are defined. PMID- 1912653 TI - Investigation and management of non-cardiac chest pain. AB - Recurring substernal chest pain is an important clinical problem, causing anxiety for patients and their physicians because of the fear of possible cardiac disease. The differential diagnosis includes coronary artery disease, oesophageal disorders such as acid reflux disease and motility disturbances, musculoskeletal problems, psychological disorders including panic attacks, and a new 'fly in the ointment'--microvascular angina. History alone usually cannot distinguish cardiac from non-cardiac chest pain. After exclusion of significant coronary artery disease, attention must be turned to oesophageal disorders, which may be seen in as many as 50% of these patients. Oesophageal motility disorders, particularly the nutcracker oesophagus, are common, but the relationship between pain and abnormal contraction pressures is not well established. Provocative tests such as edrophonium (Tensilon) and balloon distension help to identify the oesophagus as the source of chest pain but do not direct therapy. Recent studies with ambulatory oesophageal monitoring suggest that gastro-oesophageal reflux may be a more common cause of chest pain than motility disorders. This is an important finding as acid reflux is a treatable problem, while therapies for motility disorders may only worsen reflux disease. The recent observation that oesophageal disorders are frequently associated and interact with psychological disorders such as anxiety, depression, somatization and panic attacks complicates the evaluation and understanding of chest pain. How these various abnormalities may be linked is an unresolved issue. Increased central nervous system stimulation and altered visceral and/or central pain sensitivity could be the common factors. It is hoped that further research into these areas will lead to new understandings of and possible solutions to the complex problem of non-cardiac chest pain. PMID- 1912654 TI - Achalasia, diffuse spasm and non-specific motor disorders. AB - Achalasia is the best understood of the motor disorders described in this chapter. The pathogenesis involves loss of intramural neurones, a process that subsequently results in poor lower sphincter relaxation and atony of the oesophageal body. Treatment is appropriately focused on mechanical or pharmacological alleviation of LOS obstruction. In contrast, the pathophysiology of DOS and the non-specific disorders remains poorly understood. Some of the non specific disorders, such as the vigorous contraction wave abnormalities (including 'nutcracker oesophagus'), appear closely related to DOS. Treatment for patients with these findings has been based on assumptions about mechanisms of symptom production. The non-specific disorders are common in referred patients with oesophageal symptoms, and the importance of these findings deserves further study. We use a method for categorization of these manometric abnormalities which aids understanding of this difficult area and recommend its more widespread use. PMID- 1912655 TI - Gastro-oesophageal reflux disease in adults and children. PMID- 1912656 TI - Disordered gastric emptying: mechanical basis, assessment and treatment. PMID- 1912657 TI - Biliary tract motor dysfunction. AB - Gallbladder and sphincter of Oddi motility regulates the flow of bile from the liver to the duodenum. During the interdigestive period most secreted bile is diverted into the gallbladder where it is concentrated, but a significant minority of the biliary secretion passes directly into the duodenum. Regulation of this flow is mainly via the phasic contractions of the sphincter of Oddi and the sphincter basal tone. The phasic contractions expel small volumes of fluid into the duodenum, but most of the flow occurs between the contractions and is therefore not dependent on peristaltic pumping, but rather on a small pressure gradient. During fasting, just prior to duodenal phase III activity, the gallbladder expels up to 40% of its volume and the sphincter phasic contractions increase. Following a meal, the gallbladder empties its contents, and the sphincter of Oddi resistance is reduced via a fall in basal pressure and inhibition of the amplitude of phasic contractions. Control of this activity is via an interplay of both neuronal and hormonal factors which together have an effect on both gallbladder and sphincter of Oddi motility. Abnormalities in motility are recognized for both the gallbladder and the sphincter of Oddi. Gallbladder dyskinesia is objectively diagnosed using the radionuclide GBEF. In patients with a GBEF less than 40% cholecystectomy results in relief of symptoms. In postcholecystectomy patients sphincter of Oddi dysfunction presents as either biliary-like pain or idiopathic recurrent pancreatitis. Endoscopic sphincter of Oddi manometry provides the most objective diagnostic information. In patients with a sphincter of Oddi stenosis, characterized manometrically as an elevated basal pressure, division of the sphincter results in relief of symptoms. For patients with biliary-like pain, division is performed as an endoscopic sphincterotomy, whereas for patients with idiopathic recurrent pancreatitis, a sphincteroplasty and pancreatic duct septectomy are required. PMID- 1912658 TI - Small intestinal motility and transit in disease. AB - Disorders of small intestinal motility and transit are becoming increasingly recognized partly as a result of a greater awareness of their existence and partly because suitable diagnostic methods are more widely available. Usually, the neuropathic and myopathic forms can be separated, and gut disease secondary to a generalized neuromuscular disorder can be identified by the clinician. The availability of better non-invasive methods for the diagnosis of disorders of motility and transit would greatly facilitate their management. Treatment must include the restoration and maintenance of nutrition, attempts to improve intestinal motor function and resection of any segments of localized disease. Regrettably, all such measures are ineffective in the severest cases. In the future, a greater understanding of the enteric neural control of the smooth muscle and an ability to manipulate it with novel, specific drugs or peptidergic receptor agonists and antagonists, or electrical pacing, may lead to more effective therapies. PMID- 1912659 TI - Colonic motility in humans--a growing understanding. AB - As yet, there is limited information about the relationship of colonic motility to colonic flow or transit. The overall flow in the colon is slow and highly variable. The measurement of total and segmental transit time is essential for the differentiation of motor disorders associated with delayed transit. Rapid movements of colonic contents (mass movements) occur only a few times during the day. Their motor equivalent is the giant contraction which migrates in the aborad direction at relatively high velocity. Motor activity in the colon is highly variable, with periods of contraction and motor quiescence. Contractions occur at different frequencies ranging from 2 to 13 cycles per minute. High frequency contractions are stationary. Their myoelectrical equivalent is short spike bursts. Long spike bursts result in sustained, low frequency contractions, which may migrate in both directions. Technological advances now make it possible to obtain ambulant manometric recordings from the colon for 24 h. Such studies show a circadian variation in colonic motility with increases of activity after meals and after awakening. Motor disorders of the colon are not associated with specific abnormal motor patterns. Rather, they are due to changes in the occurrence of motor patterns seen in health. In constipated patients with slow colonic transit the suppression of strong peristaltic activity is the most plausible common pathogenetic mechanism. In diarrhoeal states, propulsive activity such as the giant migrating contractions may be a major mechanism which promotes the passage of stools. There is no agreement that there is disordered basal colonic motor activity in IBS. There is, however, increasing evidence that in IBS the colon responds abnormally to eating, certain forms of stress and distension, and that this may relate to symptoms. The psychopathology of IBS patients is apparently the most important factor in the health care-seeking behaviour of the patients. No specific therapy has yet been shown to be convincingly effective. PMID- 1912661 TI - Pediatric haematology. PMID- 1912660 TI - Disordered anorectal motor function. PMID- 1912662 TI - An approach to the management of infants with impaired haemostasis. PMID- 1912663 TI - Inherited bleeding disorders. AB - Congenital bleeding disorders comprise a heterogeneous group of diseases that reflect abnormalities of blood vessels, coagulation proteins and platelets. Studies of these diseases, many of which are rare and several of which result in a mild bleeding diathesis only, have significantly increased our understanding of normal haemostasis. Two lessons have been learned. First, quantitative abnormalities of coagulation proteins and platelets are an important, but not the only, cause of significant haemorrhage; some cases of inherited bleeding disorders reflect synthesis of a dysfunctional coagulation protein or production of abnormal platelets. Diagnostic tests that reflect qualitative abnormalities are therefore important in the evaluation of selected patients with inherited bleeding disorders. Second, in occasional patients the inherited disorder is complex and reflects combined abnormalities of coagulation proteins alone or in association with platelet disorders. In clinical practice it is useful to distinguish disorders that cause significant clinical bleeding from those that cause few or no symptoms. Examples of the former include severe deficiencies of factors VIII and IX, and the homozygous forms of factor II, V, VII, X, XI, XIII, fibrinogen and von Willebrand factor. Comparable platelet disorders include the inherited thrombocytopenias with platelet counts less than 20 x 10(9) litre-1 and the homozygous forms of Bernard-Soulier syndrome and Glanzmann's thrombasthenia. The most frequently encountered mild haemostatic abnormalities include type I von Willebrand's disease, the platelet storage pool deficiency syndromes and the mild and moderate forms of haemophilia A and B; occasionally heterozygous or homozygous forms of the rarer coagulation disorders, e.g. factor XI deficiency, may present with a mild bleeding diathesis. Finally, some disorders are entirely asymptomatic, e.g. factor XII deficiency and deficiencies of other contact coagulation factors. Management of patients with inherited bleeding disorders should reflect knowledge of the specific disorder to be treated plus careful consideration of the clinical circumstance for which therapy is proposed. In all cases, once a decision to treat has been made, the safest efficacious therapy should be given (for example DDAVP in the treatment of patients with mild haemophilia A or type I von Willebrand's disease). Although blood products are now much safer and the risk of blood transmitted viral infections is low, there still remains a risk that transfusion of any blood product may be associated with serious side-effects. As a result, therapy should be given only after careful consideration of the risk: benefit ratio and not merely to treat an abnormal laboratory result.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1912664 TI - Paediatric HIV infection. PMID- 1912665 TI - The management of haemoglobinopathies. PMID- 1912666 TI - Acute leukaemias. PMID- 1912667 TI - Bone marrow transplant for acute leukaemia. PMID- 1912668 TI - Infections in the compromised child. AB - Children receiving chemotherapy for malignant diseases show different patterns of infection depending on their underlying disease and its therapy. Granulocytopenia carries the risk of bacterial infection, and also, if prolonged, of fungal infection. Impairment of cell-mediated immunity predisposes to infections with Pneumocystis carinii and is thought to be responsible for severe primary infections with varicella and measles, as well as the severe cytomegalovirus infections seen after allogeneic bone marrow transplantation. Absence or impairment of splenic function predisposes to overwhelming septicaemia with encapsulated organisms, while defects in the normal mechanical barriers to infection provide routes for bacterial and fungal invasion. Despite the lack of physical signs of a normal inflammatory response, clinical evaluation may be critical to the localization of infection in the immunocompromised child. Blood culture and biopsy remain pivotal investigations in the achievement of a microbiological diagnosis. Empirical treatment with a combination of antibiotics has been shown in comparative studies to be effective in initial management of the febrile neutropenic patient: continuing studies are evaluating the role of monotherapy and of different antibiotic combinations, particularly in the light of changing patterns of bacterial infections. Empirical antifungal therapy has been shown to be necessary for persistent or recurrent fever, particularly as persistent fungal infection may compromise the outcome of continuing cytotoxic therapy. Continuing uncertainties over many aspects of management of the infected immunocompromised child provide scope for clinical trials in parallel with trials evaluating new anticancer regimens. The use of new diagnostic methods, the role of prophylaxis, the most appropriate empirical regimen, the evaluation of new antimicrobial agents, all require careful evaluation for efficacy and safety. Perhaps the greatest dilemma of all is how far results from trials in adults can be extrapolated to paediatric practice. PMID- 1912669 TI - Transfusion and the use of blood products. AB - I have reviewed areas of development in the use of blood and blood products, placing emphasis on the complications of transfusion, particularly transmission of infection. Alloimmunization in relation to transfusion of red cells and platelets has been covered and suggestions for reducing this problem assessed. The potential methods of avoiding the infective complications have been discussed including the screening of blood for infective agents, the virucidal treatment of blood products during the manufacturing process and white cell depletion. The use of recombinant DNA technology to produce coagulation factors offers the possibility of further reducing infective risks. An area of clinical promise is the use of haematopoietic growth factors to treat bone marrow failure, either congenital or acquired, such as the myelosuppressive effects of cancer chemotherapy, and reduce reliance on blood products. The aim of the chapter is to encourage the rational use of a limited resource by considering the risks inherent in transfusion and alternative strategies. In doing this it is important to audit current and future practice, and it is suggested that reference is made to the suggestions of Hume (1989) for quality assessment and assurance in paediatric transfusion medicine. PMID- 1912670 TI - [History and new development of screening and evaluation methods of anticancer drugs used in vivo and in vitro]. AB - Screening methods for the detection of anticancer activity are of crucial importance in order to find solid tumor-specific agents. A review of past screening methods is followed by a description of present methodologies targetted toward the discovery of such agents. Finally, we discuss primary and secondary in vivo evaluation in experimental chemotherapy. PMID- 1912671 TI - [Epidemiological descriptive approach of cancer in Morocco through the activity of the National Institute of Oncology. 1986-7]. AB - The Hospital registry data of the Moroccan National Oncology Institute--which is the main structure in the field--are presented here. We collected 5,148 files between 1986 and 1987. Descriptive epidemiological aspects of the most frequent cancer sites are given. Cervix uterine neoplasia is the most common carcinoma in females (35%) followed by breast cancer (22.3%). In males, nasopharyngeal cancer accounts for 12.3%, lymphoma 10.1%, larynx cancer 8.2% and lung cancer 6.5%. These data, although, constitute a starting point to a more complete approach of cancer epidemiology in Morocco; Especially since October 1, 1990 when the population--based cancer registry of Rabbat-Sale Wilaya was started. PMID- 1912672 TI - [Modulation of the growth of cultured human mammary cancer cells MCF-7 by C19 steroids]. AB - We describe the effect of 12 C19-steroids on human breast cancer hormono dependent cell growth. 5-Androstene-3 beta, 17 beta diol and 5 alpha-androstane-3 beta, 17 beta diol are the most mitogenic Dehydroepiandrosterone, 5 beta androstane-3 beta, 17 beta diol and the two 5-androstane-3 alpha, 17 beta diol are less mitogenic. 5 alpha-Dihydrotestosterone and testosterone have no effect at physiologic doses, but can modulate MCF-7 growth at pharmacologic concentrations. Androsterone and etiocholanolone have no effect, whereas androstenedione inhibits MCF-7 cell growth. PMID- 1912673 TI - [Radiation-induced neurosarcoma. Clinical, histological and immunohistochemistry aspects]. AB - The authors report on a case of radiation-induced malignant Triton tumor eg malignant schwannoma with rhabdomyoblastic differentiation). The tumor was situated in the brachial plexus of a patient who had received irradiation therapy 20 years previously for breast carcinoma. Pathological and immunohistological features have been described: coexpression of PS100, vimentin and desmin indicate a common neuroectodermic origin. A review of the literature has been presented in order to evaluate the diagnostic and prognostic characteristics of this unusual tumor and its relationship to neurofibromatosis. PMID- 1912674 TI - [Diagnosis of local recurrence after conservative treatment of breast cancer. A comparative study of a series of 50 cases]. AB - In order to determine the diagnostic features of recurrences after conservative treatment of breast cancer, 100 files have been studied. Fifty cases of glandular recurrence have been analysed and compared to 50 control cases of same stage, age and follow-up, without recurrence. In 58% of cases, the diagnosis was established during the course of a visit requested by the patient. In 84% of the cases the recurrence was found to be within the tumorectomy zone. The significant glandular pains, mammary density and deformation, nipple retractions and the radiological evidence of microcalcifications and irregular opacities seem to be strongly indicative of recurrence. The simultaneous clinical and radiological expression of recurrence was not noted in more than 52% of cases. PMID- 1912675 TI - [Impact of induction chemotherapy in the treatment of breast cancer]. AB - Two hundred and six women with a breast cancer T2 ou T3, N0, N1, M0 were randomized. One hundred and one had mastectomy and 78 with at least one poor prognosis factor received adjuvant chemotherapy. One hundred and five received first chemotherapy and 64 out of the 105 were proposed breast conservation. Retrospectively, costs of treatment in time, trips and physical sequelae were evaluated. Treatment was ten weeks longer and trips one thousand kilometers longer in conserving therapy. The cosmetic result evaluated by a nurse was good for 95% of women with conserving therapy. A self evaluation on physical, psychological, sexual and social conditions made by 64 women, one year after the end of treatment, showed no difference between the two groups. Review of literature confirmed that the impact of treatment has to be considered and carefully evaluated. PMID- 1912676 TI - [Some reflections on patient care plans during the diagnosis and clinical evaluation of cancer]. PMID- 1912677 TI - [The therapeutic decision and its acceptance by the patient]. PMID- 1912678 TI - [Surveillance and a multidisciplinary approach]. PMID- 1912679 TI - [Planning the care of the sick child]. PMID- 1912680 TI - [An example of planning: breast cancer screening in Alpes-Maritimes]. PMID- 1912681 TI - [Institutional aspects of planning in the field of cancer in a university hospital center]. PMID- 1912682 TI - [Institutional aspects of planning in a comprehensive cancer center]. PMID- 1912683 TI - [Our experience with planning in an oncologic private practice]. PMID- 1912684 TI - [Can one learn planning in prevention and in medical care from a medical faculty?]. PMID- 1912685 TI - [Planning and Research Unit for the treatment of cancer at Grenoble University Medical Center]. PMID- 1912686 TI - [Educational value of the practice of planning]. PMID- 1912687 TI - [Deontologic aspects of planning]. PMID- 1912688 TI - [Multidisciplinary ethics and planning in clinical oncology]. PMID- 1912689 TI - [Can one reconcile planning and innovation?]. PMID- 1912690 TI - [Ethical aspects of planning during the terminal phase]. PMID- 1912691 TI - [The decision making process in oncology]. PMID- 1912692 TI - Levels of chlordane, oxychlordane, and nonachlor in human adipose tissues. PMID- 1912693 TI - Disposition of ethanol and acetaldehyde in maternal blood, fetal blood, and amniotic fluid of near-term pregnant rats. PMID- 1912694 TI - UV absorption as an approximation for cell number in in vitro toxicity testing. PMID- 1912695 TI - Solid-phase extraction and cleanup for liquid chromatographic analysis of ochratoxin A in pig serum. PMID- 1912696 TI - Simultaneous determination of hippuric acid, o-, m-, and p-methylhippuric acid, phenylglyoxylic acid, and mandelic acid by HPLC. PMID- 1912697 TI - Determination of imazamethabenz in cereal grain by enzyme-linked immunosorbent assay. PMID- 1912698 TI - Bacterial degradation of phenoxy herbicide mixtures 2,4-D and MCPP. PMID- 1912699 TI - Biodegradation of monoaromatic hydrocarbons in groundwater under denitrifying conditions. PMID- 1912700 TI - Assimilation of malathion in the Indian River estuary, Florida. PMID- 1912701 TI - A simple adsorption/dilution model for rice herbicides. PMID- 1912702 TI - Toxic effects of residual chlorine on larvae of Hydropsyche pellucidula (Trichoptera, Hydropsychidae): a proposal of biological indicator. PMID- 1912703 TI - Response of enzymes involved in the processes of antioxidation towards benthiocarb and methylparathion in cyanobacteria Nostoc muscorum. PMID- 1912704 TI - Treatment of fish with hormones: solubilization and direct administration of steroids into aquaria water using acetone as a carrier solvent. PMID- 1912705 TI - Microbial biomass and ATP in smelter-polluted forest humus. PMID- 1912706 TI - Similar effects in vivo of two aluminum salts on the liver, kidney, bone, and brain of Rattus norvegicus. PMID- 1912707 TI - Differences in the accumulated metal concentrations in two epigeic earthworm species (Lumbricus rubellus and Dendrodrilus rubidus) living in contaminated soils. PMID- 1912708 TI - Planarians in toxicology. Responses of asexual Dugesia dorotocephala to selected metals. PMID- 1912709 TI - Mutagenic potential of sediments from the Grand Calumet River. PMID- 1912710 TI - In vitro effect of fenthion on human lymphocytes. PMID- 1912711 TI - Evaluation of ultrastructural hepatic response to environmental toxicants in wild cotton rats (Sigmodon hispidus). PMID- 1912712 TI - [High-resolution computerized tomography in interstitial lung diseases: experiences with over 100 patients]. AB - The report covers experience made with high-resolution computerized tomography in examining more than 100 patients with interstitial lung disease. Small bullous lesions, tiny linear bands in fibrosis and thickening of the bronchovascular bundle can easily be demonstrated by this method. Another advantage is the early detection of ground glass opacities. Although no truly pathognomonic patterns exist, this technique significantly reduces the spectrum of differential diagnosis, especially due to its ability to detect the anatomical relationship between pathological changes and substructures of the lung. PMID- 1912713 TI - [MRT of orofacial tumors--initial clinical experiences with turbo-flash intensity studies]. AB - We examined 36 patients with carcinomas of the tongue and the floor of the mouth. In 11 cases, a clear definition of the tumor extent was not possible using T2 w. spin echo sequences and T1 w. spin echo and gradient echo sequences after injection of contrast material. This delineation was attained with Turbo-FLASH intensity-vs-time studies (Gad-DTPA). The time of acquisition of each measurement was about 1 sec. At the end of injection of Gad-DTPA, 30 measurements with a delay of 1 sec between two measurements were performed. Using this technique, a marginal zone at the boundary of the tumor of very high signal intensity was visible within first minute after Gadolinium injection. This method is not required in the case of clearly hypointense (majority of the tumors) or hyperintense (minority) lesions on T1 w. Gadolinium-enhanced SE or GE images. PMID- 1912714 TI - Is ultrasonography a reliable method for evaluation of fragment clearance after biliary ESWL? A prospective, blinded study of two independent ultrasound units. AB - Ultrasound is the preceding method for evaluation of fragmentation and subsequent fragment clearance from the gallbladder. Considering the methodological shortcomings of ultrasonography, this study was therefore designed to investigate the degree of conformity between two independent ultrasound units. In our protocol patients were evaluated for fragments two weeks and three, six, nine and twelve months after ESWL. A restricted number of experienced sonographers in two independent ultrasound units examined the patient without knowledge of the other unit's findings. A total of 62 examinations have been carried out so far. Complete or sufficient conformity with a difference in size of 0-3mm was achieved in 24 examinations. Seven examinations revealed differences of 4-13 mm. In 31 cases the diagnosis of a stone-free gallbladder has been made, but only in 25 cases this could be confirmed by the other ultrasound unit. In six examinations a small fragment of less than 5mm was found by the respective other sonographer. We conclude that the diagnoses of a stone-free gallbladder after ESWL should be reconsidered by a second independent and experienced sonographer. PMID- 1912715 TI - [Combination intestinal lavage: a conservative procedure for colonoscopy]. AB - The purpose of this study was to optimize the cleaning for colonoscopy. We compared a combination of senna pods and Goleytely solution to the exclusive ingestion of 7 litres of Goleytely solution. Test parameters were the score of visual assessment in five regions of the large bowel, the distension of the abdomen, concentration of hydrogen and methane in intestinal gases and subjective informations about abdominal complaints. We concluded from 80 colonoscopies that the combined procedure was almost identical with the cleaning by voluminal ingestions of Goleytely solution. There were no differences in the scores of visual assessment or concerning the intestinal gases. The additional administration of simethicone resulted in a statistically significant decrease of foam production. Thus, the combination of senna pods, a reduced ingestion of Goleytely solution supplemented with simethicone can be recommended for colonoscopy. PMID- 1912716 TI - Focal involvement of malignant lymphoma in the liver. AB - In this study the sonographic findings of 30 patients with hepatic lymphoma have been reviewed. Lesions have been confirmed by autopsy (n = 1), laparatomy (n = 1), sonographically guided biopsy (n = 15), and during long-term follow-up (n = 13). Ten patients had Hodgkin's disease (HD) and 20 non-Hodgkin lymphomas (NHL). Focal lesions, less than 3 cm in diameter, were seen in 20 patients. The remaining ten cases presented large-nodule transformation of the parenchymal texture. All lesions were predominantly hypoechoic with a halo sign in two cases. No diffuse involvement of the liver was observed, and no correlation between histological lymphoma subtyping and patterns of hepatic infiltration was found. PMID- 1912717 TI - [Duplex sonography in ophthalmology: current approaches to research and perspectives]. AB - Duplex ultrasound imaging combines the investigation of morphological structures and hemodynamic data analysis. In ophthalmology the technique permits a non invasive evaluation of retinal and orbital vascular disorders for diagnostic purposes as well as the quantitative measurement of vascularity in intraocular and orbital tumors. We present current approaches to quantitate velocity patterns in the ophthalmic and retinal artery by Duplex ultrasound imaging. Results and clinical applications of Duplex ultrasonography studies designed to characterize the vascular network in intraocular and orbital tumors are reviewed. PMID- 1912718 TI - Sonographic investigation in the diagnosis of intrasplenic fluid collections. AB - The authors report about the diagnosis of 55 patients for whom cyst-like lesion sites or predominantly anechoic lesions were diagnosed by means of sonography of the spleen. Sonographic analysis included interventional sonography with fluid aspiration in accordance with diagnostic and therapeutic guidelines (n = 19), catheter drainage (n = 3), B-mode pulsed Doppler-Ultrasound, and short-term follow-up examinations. The final diagnoses were splenic cysts (n = 25), splenic ruptures (n = 10), splenic infarctions (n = 12), splenic abscesses (n = 7) and splenic metastasis (n = 1). Because of the ultrasound findings in diagnosis and during the follow-up observations, 15 patients underwent splenectomy. Special attention is drawn to the clinical relevance of these procedures for diagnosis of splenic liquid masses. PMID- 1912719 TI - [Diagnosis and problems in follow-up of tumors with psammoma bodies]. AB - Psammombodies are dystrophic calcifications with high density in CT being helpful to detect even small metastases. Examination should be done without oral administration of iodine to prevent mimicking metastases in contrasted bowel loops. In 3 cases with seropapillary carcinoma radiologic findings including scintigraphy and problems of diagnosis and follow-up are discussed. PMID- 1912720 TI - [Symposium "Value and performance of modern imaging procedures" at the 97th Congress of the German Society of Internal Medicine 6-10 April 1991 in Wiesbaden]. PMID- 1912721 TI - Identification and quantification of lipids from rabbit Harderian glands by gas chromatography/mass spectrometry. AB - Lipids from hydrolysed extracts of Harderian glands from the rabbit were examined as trimethylsilyl, acetonide, nicotinate and picolinyl esters and shown to consist mainly of acylated glycerol ethers and acylated hydroxy-glycerol ethers. Constituents amounting to 98.8% of the recovered secretion were identified. Fatty acids were mainly normal, saturated compounds with chain lengths from 12 to 24 carbon atoms; n-16:0 and n-18:0 accounted for about 40% of the identified acids. Small concentrations of iso-17:0 and unsaturated acids with 18-carbon chains were also identified. Fatty alcohols were again mainly normal-unsaturated compounds; the chains varied from C18 to C25 with 20:0-OH and 22:0-OH being the most abundant. Three types of 1-alkyl glycerols were found. The major constituents had normal, saturated chains with from 14 to 23 carbon atoms with the even carbon chains predominating. These were accompanied by hydroxylated derivatives of the 16- and 18-carbon glycerol ethers with hydroxy groups in the 10, 11 and 12 positions. Branched-chain glycerol ethers were of low concentration and contained predominantly iso chains. Many of these compounds have not been reported before in this secretion. Low concentrations of the previously reported hydroxy acids with n-C14, -C15 and -C16 chains were also found. Nicotinate derivatives were applied to the structural determination of glycerol ethers for the first time and shown to reveal the position of methyl branch points in an analogous manner to that previously shown for mono- and di-hydric alcohols. Acids were identified as picolinyl esters. PMID- 1912722 TI - Effect of a dual-head short-stroke pump on post-column peroxyoxalate chemiluminescence detection. AB - A dual-head short-stroke pump has two advantages in the post-column peroxyoxalate chemiluminescence (PO-CL) detection system. The first is to increase the mixing efficiency of solutions. The second is to increase the stability of the PO-CL reaction by keeping the aryl oxalate and hydrogen peroxide solutions separate. The detection sensitivities for six polycyclic aromatic hydrocarbons (PAHs) increased in the present system by using bis(2,4-dinitrophenyl) oxalate (DNPO) or bis(2,3,4,5,6-pentafluorophenyl) oxalate (PFPO) instead of such popular aryl oxalates as bis(2,4,6-trichlorophenyl) oxalate (TCPO) and bis[2-(3,6,9 trioxadecyloxycarbonyl)-4-nitrophenyl] oxalate (TDPO). Both DNPO and PFPO increased the sensitivities by factors of 4.1-10.2 and 3.5-8.1, respectively. In addition, DNPO was more stable than PFPO in acetonitrile. These results suggest that DNPO is the most useful aryl oxalate for the sensitive PO-CL detection of PAHs. PMID- 1912723 TI - Medium- and long-chain 3-hydroxymonocarboxylic acids: analysis by gas chromatography combined with mass spectrometry. AB - Medium- and long-chain 3-hydroxymonocarboxylic acids represent intermediates in the beta-oxidation of fatty acids: they accumulate in the plasma of patients with an inherited deficiency of long-chain 3-hydroxyacylcoenzyme A dehydrogenase. 3 Hydroxy acids with chain lengths varying from 6 to 16 were synthesized by a Reformatzky reaction. Capillary gas chromatography of the pertrimethylsilyl derivatives was performed on a CP-Sil 19 CB column, coupled to a quadrupole mass spectrometer in the electron impact mode. Calculation of the retention indices showed that the separation of the 3-hydroxy acids from the homologous straight chain fatty acids may be troublesome, stressing the need for mass spectrometric identification. PMID- 1912724 TI - Direct diagnosis of tuberculosis by computer assisted pattern recognition gas chromatographic analysis of sputum. AB - Chemical detection of tuberculosis (TB) products in sputum was attempted by using gas chromatographic analysis in conjunction with different pattern recognition computer models. For the chromatographic separations, we used a 2 mm x 1.8 m packed column and a 0.25 mm x 30 m fused silica capillary column to analyse the methylated glycosides and fatty acid methyl ester derivatives. Three computer pattern recognition methods were applied: error score, TB score and discriminant analysis. These methods predicted the presence of active TB most often in sputa of active TB patients and less so in those from inactive, suspected and non-TB patients, in that order. Although the best true positive of 75% was obtained from the TB score method and best true negative of 98% from discriminant analysis, the accompanying false positive and false negative results (36% and 50%, respectively) were unacceptable. The use of capillary column or fatty acid methyl ester derivatives of the samples did not improve on the predictive values of chromatograms obtained from the packed column on trimethylsilylglycosidic derivatives. Additional work is needed before this method can have a direct clinical application. PMID- 1912725 TI - A high performance liquid chromatographic assay for AMP-deaminase activity in the erythrocytes of healthy subjects and patients with inherited purine disorders. AB - A novel method for measuring AMP-deaminase activity in human erythrocytes is presented, based on the determination of the reaction product, IMP, using high performance liquid chromatography. IMP formation was found to be proportional both to the incubation time and the amount of haemolysate over a wide range. The minimal detectable AMP-deaminase activity was more than 1000 times lower than the mean activity found in healthy controls (1083 nmol/h/mg Hb). No marked difference of activity was found in the patients with the following inherited purine disorders: familial juvenile gouty nephropathy and deficiencies of adenosine deaminase, hypoxanthine-guanine phosphoribosyltransferase or adenine phosphoribosyltransferase. The activity in the erythrocytes of patients with chronic renal failure was also similar to controls. The existence of subjects with low erythrocyte AMP-deaminase activity in the population has been confirmed. PMID- 1912726 TI - High performance liquid chromatography of glucose using a post-column reactor of immobilized enzyme followed by electrochemical detection (glucose-LCEC). AB - A sensitive and selective, reasonably fast method for the determination of glucose content has been developed. A glucose oxidase immobilized column was coupled to a small-size anion exchange column/borate buffer chromatograph. The hydrogen peroxide produced in the enzyme reaction was detected directly by an amperometric detector using a platinum working electrode. The detection limit was 0.03 ppm (1.5 x 10(-7) M, 3 pmol/injection). The linear dynamic range was three orders of magnitude at least. The system was stable and reproducible both in short- and long-term operation. The proposed method is suitable for analysis of complicated matrices of biological samples because of its good selectivity and sensitivity. PMID- 1912727 TI - 4-(N,N-dimethylaminosulphonyl)-7-fluoro-2,1,3-benzoxadiazole as chemilumigenic reagent for high performance liquid chromatographic peroxyoxalate chemiluminescence detection. AB - 4-(N,N-Dimethylaminosulphonyl)-7-fluoro-2,1,3-benzoxadiazole (DBD-F), presented as a fluorogenic labelling reagent for amines and amino acids, is preferred for peroxyoxalate chemiluminescence (PO-CL) detection in high performance liquid chromatography. Amino acids and epinephrine derivatized with DBD-F were separated on a reversed phase column and detected at the femtomole level by the PO-CL detection system. PMID- 1912728 TI - Alcoholic brain damage: what does it mean to patients? PMID- 1912730 TI - Broadening the base of treatment for alcohol problems: a report which deserves to be debated. "Our vision": Chapter 1 of the Institute of Medicine Report. PMID- 1912729 TI - Alcohol and alcohol problems research 16. Northern Ireland. PMID- 1912731 TI - Broadening the base of treatment for alcohol problems: a report which deserves to be debated. Will this vision be implemented? PMID- 1912732 TI - Broadening the base of treatment for alcohol problems: a report which deserves to be debated. Basic assumptions reconsidered. PMID- 1912733 TI - Broadening the base of treatment for alcohol problems: a report which deserves to be debated. The limits of treatment and importance of prevention. PMID- 1912734 TI - Broadening the base of treatment for alcohol problems: a report which deserves to be debated. Treatment for alcohol problems: an international perspective. PMID- 1912735 TI - Broadening the base of treatment for alcohol problems: a report which deserves to be debated. The importance of scientific evaluation. PMID- 1912736 TI - Broadening the base of treatment for alcohol problems: a report which deserves to be debated. Broadening alcohol treatment in the US. PMID- 1912737 TI - Broadening the base of treatment for alcohol problems: a report which deserves to be debated. "I must be talking to my friends": the need for dialogue in dealing with alcohol problems. PMID- 1912738 TI - High retention rates within a prospective study of heroin users. AB - The process of achieving a high retention rate of subjects in a 12-month prospective study of intravenous heroin users in Sydney, Australia is presented. Self-referred heroin users were compared with heroin users from a court diversion programme. The retention rates throughout the prospective study interview schedules were high, ranging from 69 to 83% of the original sample. No statistical differences were detected between the proportions located at each interview, indicating a high retention rate was maintained despite the passage of time. It is argued that contact with State services, i.e. Methadone Maintenance Programmes and the legal system, particularly the prison service, contributed to this high maintenance. It is speculated that the effectiveness of location strategies reflect prominent characteristics of the populations studied. PMID- 1912739 TI - Superior outcome of females over males after brief treatment for the reduction of heavy drinking: replication and report of therapist effects. AB - The procedures and findings of a previous study were replicated. Sixty-one men and 35 women were randomized to one of three treatments: Manual: three sessions of instructions in use of a manual describing a step-by-step method for attaining abstinence or moderate drinking. GUIDELINES: three sessions of advice using a pamphlet summarizing the contents of the manual. Therapist: application of the step-by-step method in an indefinite number of sessions. At 3-month follow-up, the number of Moderate drinkers was again significantly higher among women than men in the GUIDELINES (77% versus 24%) and Manual conditions (75% versus 33%), but not in the Therapist condition (50% versus 53%). Again, at 1-year more women than men were Moderate drinkers in all conditions (69% versus 31% overall). Changes from baseline in GGT, MCV, and the Digit Symbol Test corroborated the clients' reports of drinking. In this study the more experienced therapists had significantly lower rates of client dropout than the less experienced. Clinical and research implications of the findings are discussed. PMID- 1912740 TI - Alcohol, social factors and mortality among young men. AB - In a 20-year follow-up the association between alcohol consumption, social and personal background factors and mortality was studied in a cohort of 49,464 Swedish conscripts. The relative risk of death among high consumers (those consuming more than 250 g alcohol/week at conscription) was 2.8 (95% confidence interval 2.2-3.7) compared with moderate consumers (1-100 g/week). Deaths caused by direct toxic effects of alcohol were few, less than 5%. Instead suicides and accidents predominated. Abstainers had a slightly lower mortality than moderate consumers, with a relative risk of 0.8 (0.6-1.1), due to a significantly lower risk for traffic deaths. High consumers of alcohol had more than twice as many social and personal risk factors for premature death compared with the cohort as a whole. Yet presence of social risk factors added little to the already increased relative risk of death among high consumers. PMID- 1912741 TI - Alcohol problems among women in a general hospital ward. AB - This paper reports a study which was conducted to establish the utility of a screening procedure consisting of a structured interview and blood tests (GGT and MCV) to detect early problem drinking in female patients in a short-stay general hospital ward. The proportion of women identified by the interview schedule was found to be greater than has been reported in general practice and some other studies of female problem drinking. However, most of the blood tests were normal for this group. Excessive alcohol consumption was significantly associated with attempted suicide by drug overdose. PMID- 1912742 TI - Alcohol and drug use in a Scottish cohort: 10 years on. AB - This paper reports the findings from a survey which elicited detailed information on patterns of alcohol use amongst a cohort of young adults. It is the fourth wave of data collection in a longitudinal study which began in 1979 on a study group of 1036 15-16 year olds attending schools in the Lothian region of Scotland. The longitudinal analysis presented here suggests that for this cohort, patterns of alcohol use at age 15-16 bear little relation to those at age 24-25 years. These findings are discussed, and compared in detail with the more limited alcohol data from the larger-scale National Child Development Study. PMID- 1912743 TI - The cue-responsivity phenomenon in dependent drinkers: 'personality' vulnerability and anxiety as intervening variables. AB - The cue-responsivity phenomenon to alcohol-associated stimuli in dependent drinkers was examined. In accordance with previous research, significant differences on both physiological and subjective cue-responsivity variables, between dependent and non-dependent drinkers were found. The unique contribution of this paper is two-fold. Firstly, evidence is presented which suggests that the Eysenckian personality traits of introversion and neuroticism are more predictive of cue-responsivity variance in the dependent drinkers than either severity of dependence or number of years' drinking. Secondly, within this dependent group, the relationship between cue-responsivity and 'craving' was seen to be less straightforward than traditionally thought. Specifically, it suggested that it was the extent to which autonomic cue-responsivity elicited increases in self reported anxiety, which predicted most of the variance on the 'craving' variable. Taken together, these results raise the interesting possibility that a personality disposition akin to trait anxiety, and the degree to which cue exposure elicits state anxiety, mediated the relationship between cue responsivity and 'craving' in dependent drinkers. PMID- 1912744 TI - Treatment of drug-dependent patients, 1968-1969. AB - Attention has been given from time to time to the question of what happened in drug-dependence clinics in the early days of their operation. It has recently come to my attention that records of meetings of consultants, held at the Department of Health, during that period, have not been kept. The following memorandum was submitted by me to a meeting held on 8 September 1969 under the title 'Practical matters relating to the treatment of drug-dependent patients'. Unfortunately, I have no record of the comments made on it, but I do not recall any major disagreement with this statement. I hope that this document, reprinted below in full, may be of historical interest. PMID- 1912745 TI - Training issues. PMID- 1912746 TI - Addiction as an occupational hazard: 144 doctors with drug and alcohol problems. AB - Information was abstracted from the hospital notes of 144 doctors who had received treatment for drug and alcohol dependency. These problems affect those in every specialty, and at all degrees of seniority. Over half came into treatment following medical referral. Social morbidity was an important contributory reason for seeking help. The mean age at presentation was 43.1 years; the mean duration of problematic use prior to this was 6.4 years for drug misusers and 6.7 years for alcohol misusers. Alcohol was the current problem for 41.6% and drug misuse for 26.4%; 31.3% were misusing both alcohol and drugs at presentation. Of the 83 subjects who were misusing drugs, only four had ever used blackmarket supplies. Psychotropic agents are readily available to doctors, but the consequences of this are not addressed. Those who develop dependency suffer a delay of years before reaching help. PMID- 1912747 TI - Evaluation of patients treated for pathological gambling in a combined alcohol, substance abuse and pathological gambling treatment unit using the Addiction Severity Index. AB - Seventy-two pathological gambling patients were followed-up after treatment in a combined alcohol, substance abuse and compulsive gambling treatment program. The Addiction Severity Index (modified for use with pathological gamblers) was used to evaluate the effectiveness of treatment. Patients reduced their intake of alcohol, other drugs and their gambling as well as improved in legal, family/social, and psychological functioning. There was a trend for improvement in medical condition and no net change in employment functioning. The study supports the idea that combined treatment is an effective way of dealing with patients whose gambling problems are discovered when they enter treatment for another addiction, as well as for patients whose initial complaints include pathological gambling, with or without additional problems. PMID- 1912748 TI - Improved CO monitors for validating smoking abstinence by expired-air carbon monoxide levels. PMID- 1912749 TI - Alcohol and alcohol problems research. 17. Malta. AB - This article is an enquiry into the current status of alcohol in Maltese culture. The responses of society to alcoholism depend on the way members of the community perceive the problems incurred by the use and abuse of a dependence producing substance like alcohol. These perceptions and subsequent responses are very much influenced by prevailing attitudes and beliefs. Malta is a melting point of cultures. This factor, together with a high density population and Malta's geopolitical strategic position, combine to make Malta a tolerant society. There is a laissez-faire response to alcoholism, at least partly due to the present inability to identify the need to take appropriate measures. The police force, medical profession and politicians still do not feel the responsibility or the need to provide effective laws and regulations, specialized treatment services or educative programmes on alcohol-related issues. A systematic enquiry is needed urgently to determine the severity and degree of the problems posed by alcohol abuse among the Maltese. Such an enquiry should be followed by a well planned national policy which includes local approaches and interventions. Finally, these interventions must be evaluated frequently and developed to achieve better results in the future. PMID- 1912750 TI - The social costs of smoking revisited. AB - This article may be read as a comment on and extension to the recent survey of studies of the social costs of smoking in this journal by Markandya & Pearce (1989), covering some aspects of the literature not included in that survey. Inevitably, there is a considerable amount of overlap with the material in several of the listed references, including the Markandya & Pearce (1989) survey. The article argues that the published studies based on the incidence approach to the costs of smoking, even on their own terms and accepting the stated assumptions, are erroneous, yielding cost estimates that are too high. In the appendix a simple model of the use of taxation to correct for informational error concerning a risky good is presented. PMID- 1912751 TI - Alcohol and other drugs: the response of the political and medical institutions. AB - Formal and informal social control in shaping individual behaviors toward the use of alcohol and other drugs is discussed. Emphasis is placed on formal social control as it occurs in two major institutions. The state, which embodies the political and legal structures of the society is discussed in terms of the social control of some of the consequences of drinking, such as public drunkenness, alcoholism, operating vehicles with specific blood alcohol levels, and crime and alcohol use. The medical institution's involvement in alcohol and drug control is discussed in terms of the physician's role in diagnosing alcohol and drug dependent individuals. Two contemporary cases, those of pregnant addicts and alcohol-related organ transplant patients, illustrate the significant interactions between the responses of the political and medical institutions, and the broader influences that help shape these responses. PMID- 1912752 TI - Should opiate addicts be involved in controlling their own detoxification? A comparison of fixed versus negotiable schedules. AB - This study compares the responses of opiate addicts at a London drug treatment centre to two outpatient methadone-based detoxification programmes. These involved either a fixed (non-negotiable) dose reduction schedule or a flexible, negotiable withdrawal schedule. In the negotiable condition, subjects were less likely to complete the detoxification programme and the mean reduction in dose achieved by the subjects in the negotiable condition was less than that in the fixed group. There was no difference between groups in programme retention at 6 weeks though subjects who remained in treatment in the negotiable group tended to extend their detoxification period beyond this point. The overall response of subjects in both groups was unsatisfactory. Only 13% of the subjects initially allocated to detoxification or 28% of those who actually started detoxification completed treatment; urine screening showed that heroin abuse was a continuing problem during treatment. The implications of these results for detoxification and drug treatment services are discussed. PMID- 1912753 TI - Follow-up after a six-month maintenance period on naltrexone versus placebo in heroin addicts. AB - Naltrexone and placebo as adjuvant treatment of opioid dependence were compared in a double-blind, controlled clinical trial in 50 heroin addicts. The overall efficacy was assessed by the degree of treatment acceptance, percentage of relapse in heroin consumption, presence of side effects, and overall retention on naltrexone. A total of 50 patients of both sexes, aged from 18 to 30 years, who fulfilled DSM-III-R criteria for opioid dependence were included in the study. All patients completed detoxification with clonidine on an inpatient basis for 2 weeks and subsequently, on an out-patient basis, received oral naltrexone (350 mg per week) for a month. At the beginning of the second month patients were randomly allocated to treatment with naltrexone (28 patients) or placebo (22 patients) until a 6-month treatment period in a double-blind fashion had been completed. During the study period (1 year) all patients followed the same therapeutic schedule. Patients in both groups were comparable in terms of socio demographic data and toxicological history. The efficacy of naltrexone was not superior to that of placebo as there were no significant differences in acceptance of treatment, retention rates, opioid and other drug consumption, drug compliance or side effects. PMID- 1912754 TI - Substance use and problems among Toronto street youth. AB - The extent of substance use and problems among adolescent 'street' and homeless populations is largely undocumented. This study describes the prevalence of drug use among a sample of 145 adolescent street youth interviewed during February and March 1990 in Toronto, Canada, and compares these data to those derived from other adolescent street and mainstream populations. PMID- 1912755 TI - Autotransplantation in solid tumors. AB - Studies are described of high-dose therapy in metastatic breast cancer, early stage breast cancer, stage IV neuroblastoma, recurrent or bulky disease testicular cancer and Ewing's sarcoma. The outcome in these subgroups with conventional therapy is described for comparison. The results of these studies suggest that high-dose therapy with autologous marrow support increases the proportion of patients with long-term survival without evidence of disease. Newer supportive care and recurrent high-dose therapy cycles of non-cross resistant regimens may improve outcome further in these diseases and increase the application to more resistant tumors. PMID- 1912756 TI - Costs of bone marrow transplants using unrelated donors. AB - Bone marrow transplantation is an expensive treatment, rationed primarily by the availability of donors. Recruiting potential unrelated bone marrow donors to a register would add not only to the cost, but also to the volume, of transplantation. Proposals to establish such registries have thus been subject to rigorous financial scrutiny. In Australia, 3 alternative estimates suggest that approximately 200 patients, otherwise suitable for bone marrow transplantation, do not receive transplants because they have no suitable related donor. The population of Australia is approximately 16 million. The alternatives for these patients are thus chemotherapy or unrelated bone marrow transplantation. The costs of chemotherapy and transplantation have been directly compared in 1 trial of treatment for acute nonlymphoblastic leukaemia. The cost per year of life saved was approximately the same for the 2 treatments, with better patient survival from transplantation. The estimated cost difference in both the United States and Australia, between the policy extremes of no patients transplanted, and all transplanted, was between 1.3-2.4% of the total costs of managing these patients. The cost of searching existing registers for unrelated donors for Australian patients, averages A$24,000-28,000 to the point of a successful donor procedure. The cost of establishing and maintaining an Australian Register of a size predicted to find donors for half of the potential recipients, has been estimated at A$ 10,000 per donor procedure. The decision to proceed with unrelated bone marrow transplantation commits resources that are currently used by the alternative therapies. It is thus important to monitor both the costs and effects of the new approach.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1912757 TI - Chromogenic peptide substrate assays and their clinical applications. AB - Chromogenic peptide substrates were first introduced into research laboratories in the early 1970s and were quickly utilised to develop assays for the determination of enzymes, proenzymes and inhibitors of the coagulation system. These assays were gradually introduced into coagulation and clinical chemistry laboratories as laboratory tools in the diagnosis and treatment of coagulation disorders. From the knowledge of the structures of the natural substrates attacked by enzymes other than those of the coagulation system or by synthesis and random screening, substrates for enzymes of the fibrinolytic, plasma and glandular kallikrein and complement systems were produced. These allowed various research groups to develop assays for components of these systems and subsequently led to the use of these assays in studies on various clinical conditions. Substrates for activated protein C ensured that assays for this enzyme and its inhibitors could be developed and introduced into the haematological routine. With the introduction of substrates for limulus lysate not only were assays for endotoxins in clinical samples produced but the control of all disposable products and injectables for endotoxin contamination can now be effected. Initially high costs and time-consuming manual assays were a hinderence to the general acceptance of the use of chromogenic peptide substrate assays and they were only used routinely in a few specialised laboratories. With the introduction of automated and microtitre plate methods however, these assays are are now available in most hospital laboratories. Since the first chromogenic peptide substrate was described thousands of articles have been published on the use of chromogenic substrate assays to measure proenzymes, enzyme activators, enzyme cofactors and inhibitors in blood and other body fluids in normal subjects and clinical material. We have endeavoured to cover as many of these as possible in this review. PMID- 1912758 TI - The role of radiotherapy in the management of multiple myeloma. PMID- 1912759 TI - Management of pediatric non-Hodgkin's lymphoma. AB - Over the past 15 years, significant progress has been made in the understanding of the molecular mechanism involved in malignant transformation of lymphocytes as well as in the management and treatment of non-Hodgkin's lymphoma (NHL) in childhood. Cyto-histological classifications and immunophenotyping of different types of NHL have contributed to the characterisation of three major subtypes of NHL in children i.e. Burkitt's lymphoma (BL), lymphoblastic lymphoma (LL) and large cell lymphoma (LCL). Precise staging of the disease at diagnosis is necessary before the onset of the treatment and should be performed as quickly as possible. Presence of bone marrow and central nervous system (CNS) involvement are major prognosis criteria. In most cases, surgery has no therapeutic role and is required only for diagnostic procedures. Similarly, several studies have demonstrated that irradiation of various sites including the CNS does not improve survival. Thus, NHL patients are usually treated with chemotherapy alone. BL and LL have distinct clinical presentations and require completely different chemotherapy protocols. After comparable induction phases with intensive chemotherapy regimens, the former is usually treated with a short consolidation phase while the latter receives a long lasting consolidation consisting of intermittent chemotherapy for at least one year. The prognosis of stage I-II, and III-IV bone marrow negative NHL of children is excellent with respectively 95% and 75% long term survival. However, patients with concomittent CNS and bone marrow involvement in both histological subtypes have a considerably worse prognosis with only 30% long term survival.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1912761 TI - Fluoride bioavailability from immediate-release sodium fluoride with calcium carbonate compared with slow-release sodium fluoride with calcium citrate. AB - The circadian variation in serum fluoride was compared between treatment with immediate-release sodium fluoride (IR-NaF) (30 mg) and calcium carbonate (500 mg calcium) and slow-release sodium fluoride (SR-NaF) (25 mg) and calcium citrate (400 mg calcium) in seven patients with postmenopausal osteoporosis maintained on long-term fluoride treatment. During 12 h following a dose of SR-NaF, serum fluoride levels could be largely kept within the therapeutic window (believed to be 95-190 ng/ml or 5-10 mumol/l). In contrast, IR-NaF produced a wide circadian fluctuation with peak-to-trough change of about 200 ng/ml. Compared to SR-NaF, IR NaF caused a significantly higher peak fluoride concentration in serum (322 vs. 158 ng/ml), and greater area under the curve (2269 vs. 1321 ng.h/ml) and urinary fluoride (6.72 vs. 3.80 mg/12 h). Thus, fluoride absorption from IR-NaF was twice as high as that from SR-NaF. PMID- 1912760 TI - Idiopathic myelofibrosis: historical review, diagnosis and management. AB - Idiopathic myelofibrosis is reviewed from several aspects. The historical development of knowledge about this disorder is discussed, from early descriptions of extramedullary hematopoiesis associated with numerous etiologies, a debate over pathogenetic mechanisms, followed by newer evidence which placed this disorder with the myeloproliferative disorders. Evidence is presented showing that idiopathic myelofibrosis is an acquired clonal disorder in terms of the hematopoietic abnormalities, but that the marrow fibrosis is a result of non clonal disordered fibrogenesis. The clinical, laboratory and pathologic features of idiopathic myelofibrosis are discussed. The features which distinguish this disorder from the other myeloproliferative disorders, particularly chronic myelogenous leukemia are emphasized. The natural history is described together with an evaluation of accepted and experimental therapy. PMID- 1912762 TI - The relationship of bone mineral density and anthropometric variables in healthy male and female children. AB - The relationships among bone mineral measurements at hip, wrist, and spine sites and anthropometric measurements which provided estimates of frame size, skinfold thickness, and muscularity were examined in a population of 140 children. The average age of the children at the time of measurement was 9.5 +/- 2.5 years and all subjects were white. In this study population, the anthropometric measurements were generally highly intercorrelated. Univariate correlations among bone mass and density variables at the different sites were also high, especially in the female children. Model fitting procedures were employed to separate the effects of age, frame size, and fatness on the bone mass measures. Resulting models confirmed previous results which suggest that height is the best predictor of bone mass in children. As expected, models for bone mineral content and bone mineral density were similar. Models for hips and wrist sites were also similar in including an estimate of frame size, while in those for the spine hip circumference explained a greater percentage of the variance. It appears that there are several identifiable characteristics among the anthropometric variables which appear to exert differential effects on skeletal development in children. PMID- 1912763 TI - Bone density changes during pregnancy and lactation in active women: a longitudinal study. AB - Six healthy active women, aged 28-34, had bone mineral density (BMD) measured (DPA & SPA) at seven sites prior to pregnancy, within 6 weeks of parturition, and after 6 months of lactation. Twenty-five nonpregnant women of the same age, height, weight, activity level and calcium intake were tested during the same period. Average calcium intake during pregnancy was 1526 mg/day; during lactation, 1622 mg/day. The nonpregnant women averaged 1756 mg/day. BMD decreased in the femoral neck (P less than or equal to 0.05) and radial shaft (P less than or equal to 0.05) during pregnancy but increased in the tibia (P less than or equal to 0.05). A 3.3% decrease in lumbar BMD during pregnancy returned to pre pregnancy values during lactation. Bone loss at the femoral neck continued during lactation (P less than or equal to 0.05). Changes in BMD during pregnancy and lactation may represent changes in mechanical stress as a result of weight gain, changes in posture and/or activity, or some other factor specific to this population of active women. PMID- 1912764 TI - Cytokine production by peripheral blood cells in postmenopausal osteoporosis. AB - It has been suggested that the release of cytokines with bone-resorbing activity from cells of the immune system might have a role in the pathogenesis of osteoporosis. We measured the secretion of the bone-resorbing products tumor necrosis factor, interleukin 1 beta and PGE2 by peripheral blood mononuclear cells from seven healthy postmenopausal women and 12 patients with postmenopausal osteoporosis. No differences were observed between both groups either in unstimulated cultures or in cultures activated with calcitriol, endotoxin or phorbol esters. These results give no support for a role of peripheral blood immune cells in postmenopausal bone loss. PMID- 1912765 TI - Histomorphometric assessment of trabecular bone remodelling in osteoporosis. PMID- 1912766 TI - Investigations: how to get from guidelines to protocols. PMID- 1912767 TI - Withdrawing antihypertensive treatment. PMID- 1912769 TI - Asking about HIV. PMID- 1912768 TI - American legislation on AIDS. PMID- 1912770 TI - Truth or dare? PMID- 1912771 TI - NIH "confused" about ethics rules. PMID- 1912772 TI - Cocaine and HIV. PMID- 1912773 TI - Review of neonatal screening programme for phenylketonuria. AB - OBJECTIVE: To review the neonatal screening programme during 1984-8. DESIGN: Analysis of data from screening laboratories and paediatricians. SUBJECTS: All live births in United Kingdom. MAIN OUTCOME MEASURES: Structure of programme; number of infants tested and number with phenylketonuria; number of infants missed; ages at testing and treatment. RESULTS: The proportion of infants tested approached 100%. The incidence of phenylketonuria was 11.7/100,000 births (445 subjects): 273 had classic phenylketonuria and three had defects of cofactor metabolism. One child with phenylketonuria was known to have been missed compared with three in 1979-83 and six in 1974-8. Seven subjects had been missed over the 15 years due to negative test results. All seven had been tested with the bacterial inhibition assay, although only 53% of infants had been so tested; the difference between the expected and observed proportion was significant (Fisher's exact test, p = 0.017). Eleven infants with classic phenylketonuria were not tested by 14 days of age and 23 (8%) did not start treatment until after 20 days, an improvement compared with 36 (15%) in 1979-83. There were, however, wide regional variations (0% to 27% treated after 20 days). CONCLUSION: The screening programme achieves high coverage and effectiveness, although some children are still missed. A national practice for screening may help reduce regional variations. PMID- 1912774 TI - Imported and autochthonous kala-azar in France. AB - OBJECTIVE: To study the epidemiological, clinical, and biological features of imported and autochthonous kala-azar in France. DESIGN: Prospective survey of all patients in France with kala-azar diagnosed over the two years 1986-7. Information was obtained from parasitology laboratories in regional hospitals and all hospital laboratories and haematology departments capable of diagnosing leishmaniasis in the south of France. SETTING: 107 public hospitals in France. PATIENTS: 89 patients with kala-azar. INTERVENTIONS: All patients were treated with drugs. In the first instance meglumine antimonate was given to all but two patients. MAIN OUTCOME MEASURES: Prevalence of the various clinical and biological features of kala-azar; proportion of patients with HIV infection. RESULTS: Half (44) of the patients were children under 8 years old. Seventy patients acquired the disease in France. Imported kala-azar was acquired mainly in Mediterranean countries (9/18 cases). Only 46 (52%) of the patients had all three of the classic associated clinical features of fever, splenomegaly, and hepatomegaly. Anaemia was the commonest biological sign, and the association of the four usual biological signs--anaemia, leucopenia, thrombocytopenia, and hypergammaglobulinaemia--was present in only 14 (33%) of the children under 8 and 26 (60%) adults. Fourteen of the patients over 8 years old were infected with HIV. CONCLUSION: Doctors must be aware of kala-azar in Mediterranean areas, especially as patients often present without the characteristic features and the disease affects young children preferentially. PMID- 1912775 TI - Treatment needs of prisoners with psychiatric disorders. AB - OBJECTIVE: To describe the prevalence of psychiatric disorder and the treatment needs of sentenced prisoners in England and Wales. DESIGN: Population survey based on a 5% sample of men serving prison sentences. SETTING: Sixteen prisons for adult males and nine institutions for male young offenders representative of all prisons in prison type, security levels, and length of sentences. SUBJECTS: 406 young offenders and 1478 adult men, 404 and 1365 of whom agreed to be interviewed. MAIN OUTCOME MEASURES: History of psychiatric disorder, clinical diagnosis of psychiatrist, and required treatment. RESULTS: 652 (37%) men had psychiatric disorders diagnosed, of whom 15 (0.8%) had organic disorders, 34 (2%) psychosis, 105 (6%) neurosis, 177 (10%) personality disorder, and 407 (23%) substance misuse. 52 (3%) were judged to require transfer to hospital for psychiatric treatment, 96 (5%) required treatment in a therapeutic community setting, and a further 176 (10%) required further psychiatric assessment or treatment within prison. CONCLUSIONS: By extrapolation the sentenced prison population includes over 700 men with psychosis, and around 1100 who would warrant transfer to hospital for psychiatric treatment. Provision of secure treatment facilities, particularly long term medium secure units, needs to be improved. Services for people with personality, sexual, and substance misuse disorders should be developed in both prisons and the health service. PMID- 1912776 TI - Stopping treatment in patients with hypertension. PMID- 1912777 TI - Risk of appendicectomy in occupations entailing contact with pigs. PMID- 1912778 TI - Prevalence of multiple sclerosis in five rural Suffolk practices. AB - OBJECTIVE: To determine a point prevalence of multiple sclerosis in part of Suffolk. DESIGN: Multiple source search for patients with multiple sclerosis in five general practices. Patients were reviewed and categorised by using general practice notes. SETTING: Five rural general practices in Suffolk, 12 May 1988. SUBJECTS: 31,379 patients registered with five practices. MAIN OUTCOME MEASURES: Multiple sclerosis diagnosed by a specialist. RESULTS: The search produced a provisional list of 62 eligible patients with multiple sclerosis. Review of case notes showed that 48 had probable disease, 10 early disease, and four possible disease. The probable cases gave a crude prevalence of 153/100,000 population (95% confidence interval 109/100,000 to 196/100,000). CONCLUSIONS: Although the results should be interpreted cautiously because of the small sample size, they suggest that the prevalence of multiple sclerosis in Suffolk is higher than has been estimated from hospital data. PMID- 1912779 TI - Is it permissible to edit medical records? PMID- 1912780 TI - Escape from collective denial: HIV transmission during surgery. PMID- 1912781 TI - Nightmare of extracontractual referral. PMID- 1912782 TI - Too much to swallow. PMID- 1912783 TI - Nicotine intake and Alzheimer's disease. PMID- 1912784 TI - The mysterious "urethral syndrome". PMID- 1912785 TI - Where should we train doctors in the future? PMID- 1912786 TI - MRCGP: examining the exam. PMID- 1912787 TI - Drugs, HIV, and prisons. PMID- 1912788 TI - Sexual behaviour in Scottish prisons. PMID- 1912789 TI - "Heartstart" Scotland. PMID- 1912790 TI - Enduring powers of attorney. PMID- 1912791 TI - Impaired glucose tolerance and height. PMID- 1912792 TI - Perinatal bereavement. PMID- 1912793 TI - Use of ambulances in outpatient departments. PMID- 1912794 TI - Computerisation of primary care in Wales. PMID- 1912795 TI - General practitioners' response to a postal questionnaire survey. PMID- 1912796 TI - General practitioner outpatient referrals. PMID- 1912797 TI - The BMA in agony. PMID- 1912798 TI - Angry about AIDS. PMID- 1912799 TI - Intravenous immunoglobulins. PMID- 1912800 TI - Nursing: an intellectual activity. PMID- 1912801 TI - The other genome. PMID- 1912803 TI - Tattoos. PMID- 1912802 TI - Garlic. PMID- 1912804 TI - HIV? Not me. PMID- 1912805 TI - Relation of low diastolic blood pressure to coronary heart disease death in presence of myocardial infarction: the Framingham Study. AB - OBJECTIVE: To examine the hypothesis that a J curve relation between blood pressure and death from coronary heart disease is confined to high risk subjects with myocardial infarction. DESIGN: Cohort longitudinal epidemiological study with biennial examinations since 1950. SETTING: Framingham, Massachusetts, USA. SUBJECTS: 5209 subjects in the Framingham study cohort followed up by a person examination approach. MAIN OUTCOME MEASURES: Coronary heart disease deaths and non-cardiovascular disease deaths in men and women with or without myocardial infarction relative to blood pressure. RESULTS: Among subjects without myocardial infarction non-cardiovascular disease deaths were twice to three times as common as coronary heart disease deaths. Furthermore, there was no significant relation between non-cardiovascular disease death and diastolic or systolic blood pressure. Also coronary heart disease deaths were linearly related to diastolic and systolic blood pressures. Among high risk patients (that is, people with myocardial infarction but free of congestive heart failure) death from coronary heart disease was more common than non-cardiovascular disease death. There was a significant U shaped relation between coronary heart disease death and diastolic blood pressure. Although there was an apparent U shaped relation between coronary heart disease death and systolic blood pressure, it did not attain statistical significance when controlling for age and change in systolic blood pressure from the pre-myocardial infarction level. None of the above conclusions changed when adjustments were made for risk factors such as serum cholesterol concentration, antihypertensive treatment, and left ventricular function. The U shaped relation between diastolic blood pressure and high risk subjects existed for both those given antihypertensive treatment and those not. CONCLUSIONS: These data suggest that an age and sex independent U curve relation exists for diastolic blood pressure and coronary heart disease deaths in patients with myocardial infarction but not for low risk subjects without myocardial infarction. The relation seems to be independent of left ventricular function and antihypertensive treatment. PMID- 1912806 TI - Measures of performance in Scottish maternity hospitals. AB - OBJECTIVE: To develop measures of hospital performance over time with particular reference to maternal and neonatal care by controlling for case mix. DESIGN: Analysis of computerised records of births. SETTING: Scotland, 1980-7. SUBJECTS: Over half a million singleton live births and stillbirths. MAIN OUTCOME MEASURES: Numbers of perinatal deaths and caesarean sections. RESULTS: Scottish maternity hospitals perform more or less equally with regard to perinatal mortality. When caesarean sections are considered, there is evidence that hospitals differ in their treatment of different groups of women; in two examples one hospital had an increased rate among women of parity 2 or more and another had a reduced rate of repeat caesarean section. CONCLUSIONS: Developing measures of performance over time by controlling for case mix is a valid system for monitoring hospital outcomes and activity, and allows comparison either between hospitals or with data for all Scottish maternity hospitals. Hospital profiles permit identification of differences for particular patient groups after allowance is made for other case mix variables. PMID- 1912807 TI - Cardiac arrest after massive acute fat embolism. PMID- 1912808 TI - Tattoos: a lasting regret. PMID- 1912810 TI - The health service and the general election. PMID- 1912809 TI - Effects of feedback of information on clinical practice: a review. AB - OBJECTIVE: To establish what is known about the role of feedback of statistical information in changing clinical practice. DESIGN: Review of 36 studies of interventions entailing the use of statistical information for audit or practice review, which used a formal research design. SUBJECTS: Papers identified from computer searches of medical and health service management publications, of which 36 describing studies of interventions designed to influence clinical care and including information feedback from clinical or administrative data systems were reviewed. MAIN OUTCOME MEASURES: Evidence for effect of information feedback on change in clinical practice. RESULTS: Information feedback was most likely to influence clinical practice if it was part of strategy to target decision makers who had already agreed to review their practice. A more direct effect was discernable if the information was presented close to the time of decision making. The questions of the optimum layout and quantity of information were not addressed; the 36 papers were insufficient for defining good formats for information to be used for audit or quality assurance. CONCLUSIONS: Given the cost of information processing and the current emphasis on closing the audit loop in the health services, it is important that the use of information in the audit process should be critically evaluated. PMID- 1912811 TI - Challenge of aging. PMID- 1912812 TI - Mental health. PMID- 1912813 TI - Hepatitis A immunisation. PMID- 1912814 TI - Surgeons and hepatitis B. PMID- 1912815 TI - Routine testing for HIV at infertility clinics. PMID- 1912816 TI - Child sexual abuse and HIV infection. PMID- 1912817 TI - Consequences of child sexual abuse. PMID- 1912819 TI - Hormone replacement therapy in general practice. PMID- 1912818 TI - Growth of asthmatic children. PMID- 1912820 TI - Surgeons' qualifications. PMID- 1912821 TI - Domiciliary thrombolytic treatment. PMID- 1912822 TI - Normal antenatal management. PMID- 1912823 TI - Preventing needlestick injuries. PMID- 1912824 TI - Surgeons who undertake surgery for colorectal cancer. PMID- 1912825 TI - Future of long term care of dependent elderly people. PMID- 1912826 TI - Liver transplantation after paracetamol overdose. PMID- 1912827 TI - Out of hours work in general practice. PMID- 1912828 TI - When sex is a headache. PMID- 1912829 TI - Hearing loss in adults with learning disabilities. PMID- 1912830 TI - Ames, the Ames test, and the causes of cancer. PMID- 1912831 TI - Treating bony metastases. PMID- 1912832 TI - AIDS meeting moves outside US. PMID- 1912833 TI - Fatal myocardial infarction in the Scottish adjuvant tamoxifen trial. The Scottish Breast Cancer Committee. AB - OBJECTIVE: To investigate the incidence of fatal myocardial infarction in women in the two randomised arms of the Scottish adjuvant tamoxifen trial. DESIGN: Retrospective review of hospital notes to determine with the greatest possible certainty women who had died of an acute myocardial infarction. SETTING: Scottish Cancer Trials Office, the University of Edinburgh. PATIENTS: 1070 postmenopausal women with operable breast cancer who were randomised to receive either adjuvant tamoxifen for five years or until relapse (539 patients) or tamoxifen for at least six weeks on the confirmation of first recurrence (531 patients). MAIN OUTCOME MEASURES: Incidence of fatal myocardial infarction in women with no known or suspected systemic cancer. RESULTS: Of the 200 women who died in the adjuvant tamoxifen arm of the trial, 44 were free of cancer at death and 10 of these died of myocardial infarction. In the observation arm 251 women died, of whom 61 showed no evidence of systemic cancer and 25 had a fatal myocardial infarction. The incidence of fatal myocardial infarction in the two groups was significantly different (chi 2 = 6.88, p = 0.0087). CONCLUSION: Tamoxifen given for at least five years as adjuvant therapy for breast cancer seems to have a cardioprotective oestrogen-like effect in postmenopausal women. PMID- 1912834 TI - Survival with bladder cancer, evaluation of delay in treatment, type of surgeon, and modality of treatment. AB - OBJECTIVE: To determine whether length of delay before treatment; specialty and grade of the surgeon; and use made of surgery, radiotherapy, and chemotherapy influenced the survival of patients with cancer of the bladder, after adjusting for case severity. DESIGN: Retrospective cohort study. SETTING: South East and South West Thames health regions. PATIENTS: 609 men aged under 75 resident in the South Thames regions who had been registered as new cases of bladder cancer in 1982, 35 of whom were excluded, leaving 574 eligible patients. Analysis was based on 75% retrieval rate for case notes. MAIN OUTCOME MEASURES: Duration of survival from date of diagnosis of the bladder tumour. RESULTS: 10 prognostic variables were used to adjust for case severity. The median delay from referral to first treatment was 48 (interquartile range 27-84) days. Treatment after a short delay was associated with shorter survival because of the early treatment of more severe cases. Consultants treated 68% of patients, trainee surgeons treated less severe cases. Initial treatment was by a urologist in 67% of cases, but the specialty of the surgeon was not associated with prognosis. The associations of radiotherapy, cystectomy, and systemic chemotherapy with survival were interpreted in terms of selection bias as well as therapeutic effect. CONCLUSION: Case severity was the most important influence on survival and influenced length of delay before treatment, grade and specialty of the surgeon, and main treatment allocation. After adjusting for case severity variations in these processes of care were not strongly associated with variations in survival. PMID- 1912836 TI - Deaths from Rh haemolytic disease in England and Wales in 1988 and 1989. PMID- 1912835 TI - Epidemiology of Haemophilus influenzae type b invasive disease in Wales. AB - OBJECTIVE: To investigate the epidemiology of invasive disease due to Haemophilus influenzae type b, the clones responsible, and the antibiotic resistance of the isolates. DESIGN: Prospective population based analysis of clinical and epidemiological data collected for Gwynedd during 1980-90 and in the whole of Wales during 1988-90. SETTING: 19 hospitals in Wales; all medical microbiology laboratories in Wales participated. PATIENTS: 82 patients with confirmed invasive infections caused by H influenzae type b in Gwynedd during 1980-90 and 207 in Wales during 1988-90. MAIN OUTCOME MEASURES: Clinical and epidemiological measures; analysis of the clonal types of the isolates based on the electrophoretic mobilities of 17 metabolic enzymes; and antibiotic resistance. RESULTS: The annual incidence of H influenzae type b infections in Gwynedd was 3.2 cases/100,000 and in Wales was 2.5 cases/100,000. Most cases occurred in children aged under 5 years, the highest annual incidence being in those aged under 1 (84.6/100,000 and 56.9/100,000 in Wales). The cumulative risk of acquiring H influenzae type b disease by the fifth birthday was one in 456 in Gwynedd and one in 578 in Wales. Fifteen per cent of cases in Gwynedd and 7% of those in Wales occurred in adults. Predominant clinical conditions were meningitis in children and pneumonia in adults. In Gwynedd 2/70 (3%) children and 5/12 (42%) adults died. Long term neurological sequelae occurred in 8% (4/48) of children who survived haemophilus meningitis. Children presenting with infection were usually the youngest members of their family. No secondary household cases were identified. 100 of 128 (78%) strains were of a single clone, electrophoretic type 12.5, and 4/207 (1.9%) isolates from Wales were resistant to both ampicillin and chloramphenicol. CONCLUSIONS: The annual rate of infection in children aged under 5 in four Welsh counties was 12-44% higher than that previously published for the United Kingdom. The study emphasises the potential value of a vaccine effective in early infancy and provides baseline data to assess its efficacy after its introduction. Alternatives to ampicillin and chloramphenicol should be used as first line, empirical treatment for severe infections that might be caused by H influenzae type b in Wales. PMID- 1912837 TI - Portable medical record for the homeless mentally ill. PMID- 1912838 TI - Cervical screening in Perth and Kinross since introduction of the new contract. AB - OBJECTIVE: To determine changes in the cervical screening service since the introduction of the new general practitioner contract on 1 April 1990. DESIGN: Analysis of computerised records of cervical screening both before and after introduction of the new contract. SETTING: General practices in Perth and Kinross Unit, Tayside. PATIENTS: A total of 30,071 women aged 21-60 on 26 general practitioner partnership lists. MAIN OUTCOME MEASURES: Percentage average of target population for cervical screening in each practice for first three quarters on introduction of the contract. RESULTS: Perth and Kinross Unit completed a computerised cervical screening call programme in July 1989, which produced an increase from 71% to 78% in the mean percentage of women aged 20-60 who had had cervical smear tests within 5.5 years. Six months after the introduction of the new general practitioner contract the mean population coverage was increased to 85% in women aged 21-60 and only four practices had not attained the 80% upper target compared with 10 on 1 April 1990. Detailed examination of randomly selected practices immediately before the new contract was introduced showed an average artificial list inflation of 4.3% in health board records when compared with practice records, a hysterectomy rate of 6.2%, and an additional 3% of women who were considered to be ineligible for smear testing due to putative virginity or illness or infirmity, or both. There was a considerable shift away from use of well woman clinics (2.7% of smears in 1990 compared with 5.6% in 1988) for taking cervical smears, potentially threatening the long term viability of the clinics. CONCLUSION: The introduction of the new contract for general practitioners has brought about a further sustained increase in population coverage for cervical screening in a small Scottish unit with a stable population, well motivated general practitioners, and a fully integrated computerised call and recall system based on the community health index. To optimise the screening service revision of the targets levels is necessary. PMID- 1912839 TI - Set menus and clinical freedom. PMID- 1912841 TI - Health of pregnant women. PMID- 1912842 TI - Accident prevention. PMID- 1912840 TI - Strategies for prevention of osteoporosis and hip fracture. PMID- 1912843 TI - Dog bites to children. PMID- 1912844 TI - Zidovudine after occupational exposure to HIV. PMID- 1912845 TI - Stopping treatment in patients with hypertension. PMID- 1912846 TI - HIV testing of patients with end stage renal failure. PMID- 1912847 TI - Unchanging workload in gastric cancer. PMID- 1912848 TI - Managing violence in psychiatric hospitals. PMID- 1912849 TI - Review of neonatal screening programme for phenylketonuria. PMID- 1912850 TI - What now for IPPNW? PMID- 1912851 TI - Licensing laws and drinking. PMID- 1912852 TI - Uptake of cervical smear testing among travellers. PMID- 1912853 TI - Extracontractual referrals: the story so far. PMID- 1912854 TI - Vocational training in general practice. PMID- 1912855 TI - Child placement. PMID- 1912856 TI - Consultants in communicable disease control. PMID- 1912857 TI - Long term renal outcome of childhood haemolytic uraemic syndrome. AB - OBJECTIVE: To evaluate the long term outcome of renal function in infants and children after diarrhoea associated haemolytic uraemic syndrome. SETTING: The Hospital for Sick Children, Great Ormond Street, and the Royal Free Hospital, London. SUBJECTS: 103 children with the syndrome who presented between 1966 and 1985; 88 attended for follow up investigations (40 male, 48 female) with a mean age 11.6 (range 5.2-22.6) years and a mean duration of follow up of 8.5 (range 5.1-21.3) years. MAIN OUTCOME MEASURES: Blood pressure, ratio of early morning urine albumin to creatinine concentration, glomerular filtration rate, and plasma renin activity. RESULTS: The mean (SD) systolic blood pressure standard deviation score was 0.38 (0.67) and diastolic blood pressure SD score was 0.10 (0.76). The geometric mean ratio of overnight urine albumin to creatinine concentration was 1.27 (range 0.03-48.2), significantly higher than the value observed in 77 normal children (0.32 (0.05-1.95), p less than 0.0001). Glomerular filtration rate estimated from the plasma clearance of chromium-51 EDTA was 95.1 (22.7) ml/min/1.73 m2 surface area, and 16 children had a rate of less than or equal to 80 ml/min/1.73 m2. Significant negative correlations were found between glomerular filtration rate and urinary albumin to creatinine ratio (r = -0.41, p less than 0.0001) and glomerular filtration rate and systolic blood pressure SD score (r = -0.48, p less than 0.0001). A significant positive correlation was found between urinary albumin to creatinine ratio and systolic blood pressure SD score (r = 0.25, p = 0.02). CONCLUSIONS: After an acute episode of diarrhoea associated haemolytic uraemic syndrome 31% (27/88) of children had an increased albumin excretion, 18% (16/88) had a reduced glomerular filtration rate and 10% (9/88) had both, in association with a higher systolic blood pressure, indicating considerable residual nephropathy in this group. PMID- 1912858 TI - Breast feeding and vitamin A deficiency among children attending a diarrhoea treatment centre in Bangladesh: a case-control study. AB - OBJECTIVE: To determine the effect of breast feeding on the risk of xerophthalmia in children aged 6 months to 3 years attending a diarrhoea treatment centre in Bangladesh. DESIGN: Case-control study based on stratified analysis (Mantel Haenszel) and multivariate analysis (logistic regression) of data from a treatment centre based surveillance system. SETTING: A large diarrhoea treatment centre in Dhaka, Bangladesh. PATIENTS: 2687 children aged 6 months to 3 years representing a 4% systematic sample of all children in this age group treated yearly at the centre over three consecutive years. 66 of the children were cases of xerophthalmia (that is, they had Bitot's spots or corneal lesions or night blindness or night blindness plus conjunctival xerosis or any combination of these) and the remaining 2621 did not have signs or symptoms of vitamin A deficiency. This second group served as controls. MAIN OUTCOME MEASURE: Xerophthalmia and breast fed at onset of diarrhoea or presentation. RESULTS: The odds ratio relating breast feeding to vitamin A deficiency after adjustment for a large number of confounding variables (0.26 (95% confidence interval 0.14 to 0.49); p less than 0.001) reflected a 74% reduction in the risk of vitamin A deficiency among breast fed children. The estimated reduction of risk did not decline with age, and some 49% of children aged 24-35 months were still being breast fed. The odds ratio relating breast feeding to xerophthalmia in the third year of life (0.35 (95% confidence interval 0.35 to 0.86) reflected a 65% reduced risk of vitamin A deficiency. Other important risk factors or prognostic indicators for xerophthalmia as identified by multivariate analysis were recent measles, prolonged diarrhoea, severe protein energy malnutrition, and poor socioeconomic state. CONCLUSIONS: These results indicate that breast feeding was associated with a substantial reduction of the risk of vitamin A deficiency extending to the third year of life and support the recommendation that mothers in developing countries should be advised to breast feed for as long as possible. PMID- 1912859 TI - Extracontractual referrals in first three months of NHS reforms. AB - OBJECTIVE: To describe the extracontractual referrals of residents of Merton and Sutton Health Authority during the first three months of the NHS reforms in terms of the nature of the referral (elective or emergency), the specialty referred to, and the source of and reason for referral. DESIGN: Descriptive analysis of all extracontractual referrals submitted to the health authority between 1 April and 30 June 1991. SETTING: Merton and Sutton Health Authority. RESULTS: 247 extracontractual referrals were notified to Merton and Sutton Health Authority; 83 invoices for emergency treatment and 109 elective referrals were authorised at a total cost of 190,000 pounds. Of the elective referrals, 59 were to ear, nose, and throat; orthopaedic; or general surgery departments. Local general practitioners made only two thirds of the elective referrals, at least 15 of which were made at the patient's request. Four admissions accounted for a quarter of the total cost of the emergency admissions. CONCLUSIONS: Extracontractual referrals are unpredictable in terms of both their number and their cost. They provide a necessary safeguard for patient and general practitioner choice at the price of a considerable administrative workload. The fact that these referrals are income generating for providers means that additional safeguards may be necessary to prevent abuse of the system. PMID- 1912860 TI - Dealing with extracontractual referrals. AB - OBJECTIVE: To describe the mechanism established by Richmond, Twickenham, and Roehampton Health Authority to manage extracontractual referral requests made on behalf of its resident population and to examine its working in the first three months of the new arrangements. DESIGN: Description of the procedures for managing extracontractual referrals and the decisions made on requests submitted to the district health authority between 1 April and 30 June 1991. RESULTS: 235 requests were submitted, 79 for emergency care. 156 requests were clearly for elective treatments and, of these, 61 were ultimately refused, 20 because the district health authority was not liable to pay. Of the remaining 41, 17 were appealed successfully and three unsuccessfullly. More than half of the elective extracontractual referrals correctly submitted were to either orthopaedics, general surgery, oral surgery, gynaecology, or plastic surgery. Overall, the district health authority approved three quarters of the requests for which it would be financially liable; this was the predicted workload for the period. CONCLUSIONS: The management of extracontractual referral requests is complex and time consuming for clinicians and managers alike. Patient choice is clearly being limited to some extent, but this is necessary if the number of requests is not to exceed the levels on which funding is based. PMID- 1912862 TI - Use of influenza vaccine in The Netherlands. PMID- 1912861 TI - Screening for carriers of cystic fibrosis through primary health care services. AB - OBJECTIVE: To evaluate the uptake of cystic fibrosis carrier testing offered through primary health care services. DESIGN: Carrier testing for cystic fibrosis was offered to patients of reproductive age through primary health care services. SETTING: Three general practice surgeries and four family planning clinics in South West Hertfordshire District Health Authority. SUBJECTS: Over 1000 patients aged 16-44 attending two general practices and four family planning clinics and a stratified random sample of patients aged 16-44 from one general practice's age sex register. RESULTS: When screening was offered opportunistically the uptake was 66% in general practice and 87% in family planning clinics. Ten per cent of those offered a screening appointment by letter took up the invitation. Of the screened population, 76% had previously heard of cystic fibrosis, 35% realised it is inherited, and 18% realised that carriers need not have any family history. If they found themselves in an "at risk" partnership 39% would consider not having children and 26% would consider terminating an affected pregnancy, but in each case most people were unsure how they would react. CONCLUSIONS: Most people offered a cystic fibrosis test opportunistically wish to be tested, and the responses of those tested indicate that knowledge of carrier state would be considered in future reproductive decisions. PMID- 1912863 TI - Winter pressure on hospital medical beds. PMID- 1912864 TI - General practice education: things to come. PMID- 1912866 TI - Children's health. PMID- 1912865 TI - Skin avulsion during manipulation of fractures. PMID- 1912867 TI - Cancer. PMID- 1912868 TI - New dietary reference values. PMID- 1912869 TI - Alcohol consumption and risk of coronary heart disease. PMID- 1912870 TI - Controlled trials in single subjects. PMID- 1912871 TI - Creutzfeldt-Jakob disease and blood transfusion. PMID- 1912872 TI - Investigations: getting from guidelines to protocols. PMID- 1912873 TI - Childhood diabetes and material deprivation. PMID- 1912874 TI - Deprivation indices. PMID- 1912875 TI - Psychological therapy in the NHS. PMID- 1912876 TI - Rheumatoid arthritis as an infectious disease. PMID- 1912877 TI - Twenty five years of case finding and audit. PMID- 1912878 TI - Confidentiality in medical audit. PMID- 1912879 TI - Advances in cell kinetics. PMID- 1912880 TI - The rise of post-traumatic stress disorders. PMID- 1912881 TI - Medically unexplained physical symptoms. PMID- 1912882 TI - AIDS: rights versus responsibilities. PMID- 1912883 TI - It's on the record. PMID- 1912885 TI - Change in alcohol consumption and risk of death from all causes and from ischaemic heart disease. AB - OBJECTIVE: To examine the association between alcohol consumption and mortality from all causes and from ischaemic heart disease with a focus on differentiating between long term abstainers and more recent non-drinkers. DESIGN: Cohort study of changes in alcohol consumption from 1965 to 1974 and mortality from all causes and ischaemic heart disease during 1974-84. SETTING: Population based study of adult residents of Alameda County, California. SUBJECTS: 2225 women and 1845 men aged 35 and over in 1965. MAIN OUTCOME MEASURES: Alcohol consumption in 1964 and 1974 and mortality from all causes and from ischaemic heart disease during 1974 84. RESULTS: There was a significantly higher risk of death from all causes and from ischaemic heart disease in women who gave up drinking between 1965 and 1974 than in women who continued to drink (relative risk 1.72, 95% confidence interval 1.11 to 2.66, and 2.75, 1.44 to 5.23, for all causes and ischaemic heart disease respectively). A significant increase in risk was not seen in men who gave up drinking (1.32, 0.87 to 2.01, and 0.95, 0.41 to 2.20, respectively). Among men, long term abstainers compared with drinkers were at increased risk of death from all causes and from ischaemic heart disease, though the associations were not significant (1.40, 0.98 to 2.00, and 1.40, 0.76 to 2.58, for all causes and ischaemic heart disease respectively). CONCLUSION: Some of the increased risk of death from all causes and from ischaemic heart disease associated with not drinking in women seems to be accounted for by higher risks among those who gave up drinking. Men who are long term abstainers may also be at an increased risk of death. The heterogeneity of the non-drinking group should be considered when comparisons are made with drinkers. PMID- 1912884 TI - Orthopaedic surgeons and thromboprophylaxis. AB - OBJECTIVE: To assess attitudes to the use of thromboprophylaxis among orthopaedic surgeons in the United Kingdom. DESIGN AND SUBJECTS: Single page postal questionnaire to all 926 active orthopaedic surgeons who are members of the British Orthopaedic Association. RESULTS: The response rate was 70% (659 surgeons), of whom 595 (90%) used some form of prophylaxis. Most (548; 83%) used drugs but 47 (7%) used only elasticated stockings. A history of thromboembolic disease, hip surgery, and obesity was seen as the main risk factor. Ineffectiveness was the principal reason for not using prophylaxis. CONCLUSIONS: Most orthopaedic surgeons use regimens of thromboprophylaxis, though many of these are of limited value. Improvements in the efficacy and safety of prophylactic agents, combined with ease of administration, would increase the use of such agents and make orthopaedic surgery safer for the patient. PMID- 1912886 TI - Influenza vaccination in adults with cystic fibrosis. PMID- 1912888 TI - Funding family health services. PMID- 1912887 TI - Acute red ear in children: controlled trial of non-antibiotic treatment in general practice. AB - OBJECTIVE: To examine the efficacy and safety of conservative management of mild otitis media ("the acute red ear") in children. DESIGN: Double blind placebo controlled trial. SETTING: 17 group general practices (48 general practitioners) in Southampton, Bristol, and Portsmouth. PATIENTS: 232 children aged 3-10 years with acute earache and at least one abnormal eardrum (114 allocated to receive antibiotic, 118 placebo). INTERVENTIONS: Amoxycillin 125 mg three times a day for seven days or matching placebo; 100 ml paracetamol 120 mg/5 ml. MAIN OUTCOME MEASURES: Diary records of pain and crying, use of analgesic, eardrum signs, failure of treatment, tympanometry at one and three months, recurrence rate, and ear, nose, and throat referral rate over one year. RESULTS: Treatment failure was eight times more likely in the placebo than the antibiotic group (14.4% v 1.7%, odds ratio 8.21, 95% confidence interval 1.94 to 34.7). Children in the placebo group showed a significantly higher incidence of fever on the day after entry (20% v 8%, p less than 0.05), mean analgesic consumption (0.36 ml/h v 0.21 ml/h, difference 0.14, 95% confidence interval 0.07 to 0.23; p = 0.0022), mean duration of crying (1.44 days v 0.50 days, 0.94; 0.50 to 1.38; p less than 0.001), and mean absence from school (1.96 days v 0.52 days, 1.45; 0.46 to 2.42; p = 0.0132). Differences in recorded pain were not significant. The prevalence of middle ear effusion at one or three months, as defined by tympanometry, was not significantly different, nor was there any difference in recurrence rate or in ear, nose, and throat referral rate in the follow up year. No characteristics could be identified which predicted an adverse outcome. CONCLUSIONS: Use of antibiotic improves short term outcome substantially and therefore continues to be an appropriate management policy. PMID- 1912889 TI - Alcohol and cardiovascular disease: the status of the U shaped curve. PMID- 1912890 TI - Strategy for asthma. PMID- 1912892 TI - Abortion rates still rising. PMID- 1912891 TI - HIV and AIDS. PMID- 1912893 TI - Nursing: an intellectual activity. PMID- 1912894 TI - HIV transmission during surgery. PMID- 1912895 TI - Guidelines for doctors with HIV infection. PMID- 1912896 TI - Zidovudine after occupational exposure to HIV. PMID- 1912897 TI - Complications of pregnancy and delivery and psychosis in adult life. PMID- 1912898 TI - HIV and discrimination. PMID- 1912899 TI - Child sexual abuse. PMID- 1912900 TI - Antepartum haemorrhage and cervical cancer. PMID- 1912901 TI - Availability of cadaver organs for transplantation. PMID- 1912902 TI - Breast carcinomas diagnosed in the 1980s. PMID- 1912903 TI - Mental health needs of Asians. PMID- 1912904 TI - Mandatory assessment of patients over 75. PMID- 1912905 TI - Is it permissible to edit medical records? PMID- 1912906 TI - Role of research in general practice. PMID- 1912907 TI - The BMA in agony. PMID- 1912908 TI - Blood saving. PMID- 1912909 TI - Coronary bypasses 10 years on. PMID- 1912910 TI - Showing the green card. PMID- 1912911 TI - AIDS conference moves to Amsterdam. PMID- 1912912 TI - Vaccines for HIV infected pregnant women? PMID- 1912913 TI - Relation of birth weight and childhood respiratory infection to adult lung function and death from chronic obstructive airways disease. AB - OBJECTIVE: To examine whether birth weight, infant weight, and childhood respiratory infection are associated with adult lung function and death from chronic obstructive airways disease. DESIGN: Follow up study of men born during 1911-30 whose birth weights, weights at 1 year, and childhood illnesses were recorded at the time by health visitors. SETTING: Hertfordshire, England. SUBJECTS: 5718 men born in the county during 1911-30 and a subgroup of 825 men born in the county during 1920-30 and still living there. MAIN OUTCOME MEASURES: Death from chronic obstructive airways disease, mean forced expiratory volume in one second (FEV1) and forced vital capacity (FVC), and respiratory symptoms. RESULTS: 55 men died of chronic obstructive airways disease. Death rates fell with increasing birth weight and weight at 1 year. Mean FEV1 at age 59 to 70 years, adjusted for height and age, rose by 0.06 litre (95% confidence interval 0.02 to 0.09) with each pound (450 g) increase in birth weight, independently of smoking habit and social class. Bronchitis or pneumonia in infancy was associated with a 0.17 litre (0.02 to 0.32) reduction in adult FEV1 and with an increased odds ratio of wheezing and persistent sputum production in adult life independently of birth weight, smoking habit, and social class. Whooping cough in infancy was associated with a 0.22 litre (0.02 to 0.42) reduction in adult FEV1. CONCLUSIONS: Lower birth weight was associated with worse adult lung function. Intrauterine influences which retard fetal weight gain may irrecoverably constrain the growth of the airways. Bronchitis, pneumonia, or whooping cough in infancy further reduced adult lung function. They also retarded infant weight gain. Consistent with this, death from chronic obstructive airways disease in adult life was associated with lower birth weight and weight at 1 year. Promoting lung growth in fetuses and infants and reducing the incidence of lower respiratory tract infection in infancy may reduce the incidence of chronic obstructive airways disease in the next generation. PMID- 1912914 TI - Total cholesterol, low density lipoprotein cholesterol, and high density lipoprotein cholesterol and coronary heart disease in Scotland. AB - OBJECTIVE: To investigate long term changes in total cholesterol, high density lipoprotein cholesterol, and low density lipoprotein cholesterol concentrations and in measures of other risk factors for coronary heart disease and to assess their importance for the development of coronary heart disease in Scottish men. DESIGN: Longitudinal study entailing follow up in 1988-9 of men investigated during a study in 1976. SETTING: Edinburgh, Scotland. SUBJECTS: 107 men from Edinburgh who had taken part in a comparative study of risk factors for heart disease with Swedish men in 1976 when aged 40. INTERVENTION: The men were invited to attend a follow up clinic in 1988-9 for measurement of cholesterol concentrations and other risk factor measurements. Eighty three attended and 24 refused to or could not attend. MAIN OUTCOME MEASURES: Changes in total cholesterol, high density lipoprotein cholesterol, and low density lipoprotein cholesterol concentrations, body weight, weight to height index, prevalence of smoking, and alcohol intake; number of coronary artery disease events. RESULTS: Mean serum total cholesterol concentration increased over the 12 years mainly due to an increase in the low density lipoprotein cholesterol fraction (from 3.53 (SD 0.09) to 4.56 (0.11) mmol/l) despite a reduction in high density lipoprotein cholesterol concentration. Body weight and weight to height index increased. Fewer men smoked more than 15 cigarettes/day in 1988-9 than in 1976. Blood pressure remained stable and fasting triglyceride concentrations did not change. The frequency of corneal arcus doubled. Alcohol consumption decreased significantly. Eleven men developed clinical coronary heart disease. High low density lipoprotein and low high density lipoprotein cholesterol concentrations in 1976, but not total cholesterol concentration, significantly predicted coronary heart disease (p = 0.05). Almost all of the men who developed coronary heart disease were smokers (91% v 53%, p less than 0.05). CONCLUSION: Over 12 years the lipid profile deteriorated significantly in this healthy cohort of young men. Smoking, a low high density lipoprotein concentration and a raised low density lipoprotein concentration were all associated with coronary heart disease in middle aged Scottish men, whereas there was no association for total cholesterol concentration. The findings have implications for screening programmes. PMID- 1912915 TI - A controlled study of eight months of physical training and reduction of blood pressure in children: the Odense schoolchild study. AB - OBJECTIVE: To examine the effect of physical training on physical fitness and blood pressure in children aged 9-11 years. DESIGN: Prospective randomised controlled intervention study of a sample of children drawn from a population survey of coronary risk factors in children. SETTING: Odense, Denmark. SUBJECTS: 69 children with mean blood pressure greater than or equal to 95th centile (hypertensive group) and 68 with mean blood pressure less than 95th centile (normotensive group), randomly selected from a population of 1369 children. INTERVENTION: 67 children were randomised to receive three extra lessons a week of an ordinary school physical education programme for eight months. MAIN OUTCOME MEASURES: Physical fitness assessed by calculation of maximum oxygen uptake and blood pressure recorded by one unblinded observer. RESULTS: After three months neither blood pressure nor physical fitness had changed significantly. After adjustment for values in weight, height, heart rate, and the variable in question before training physical fitness rose significantly at the end of eight months' training, by 3.7 mlO2/kg/min (95% confidence interval 2.2 to 5.3) in the normotensive training subgroup and by 2.1 mlO2/kg/min (0.1 to 4.2) in the hypertensive training subgroup compared with that in the controls. Systolic and diastolic blood pressures in the training subgroups fell significantly by 6.5 mm Hg (3.2 to 9.9) and 4.1 mm Hg (1.7 to 6.6) respectively in the normotensive group and by 4.9 mm Hg (0.7 to 9.2) and 3.8 mm Hg (0.9 to 6.6) respectively in the hypertensive group. CONCLUSIONS: Physical training lowers blood pressure and improves physical fitness in children and might have implications for an important non-pharmacological approach to primary prevention of essential hypertension. PMID- 1912916 TI - Malnutrition in prisoners admitted to a medical ward in a developing community. PMID- 1912917 TI - Topical anaesthesia in upper gastrointestinal endoscopy. PMID- 1912918 TI - Self testing for diabetes mellitus. AB - OBJECTIVE: To develop a simple, economically viable, and effective means of population screening for diabetes mellitus. DESIGN: A postal request system for self testing for glycosuria with foil wrapped dipsticks. Preprandial and postprandial tests were compared with a single postprandial test. The subjects were instructed how to test, and a result card was supplied on which to record and return the result. All those recording a positive test result and 50 people recording a negative result were invited for an oral glucose tolerance test. SETTING: General practice in east Suffolk, list size 11534. PATIENTS: All subjects aged 45-70 years registered with the practice were identified by Suffolk Family Health Services Authority (n = 3057). The 73 subjects known to have diabetes from the practice's register were excluded, leaving 2984 subjects, 2363 (79.2%) of whom responded. 1167 subjects completed the single test and 1196 the two tests. MAIN OUTCOME MEASURES: Response rate and number of patients with glycosuria. Sensitivity, specificity, and positive predictive value of a single postprandial test and preprandial and postprandial tests. Number of new cases of diabetes identified and cost of screening. RESULTS: Of the patients completing the single postprandial test, 29 had a positive result, an oral glucose tolerance test showed that eight (28%) had diabetes, six (21%) impaired glucose tolerance, and 14 (48%) normal glucose tolerance. 44 of the group who tested before and after eating had a positive result; nine (20%) had diabetes, five (11%) impaired tolerance, and 26 (11%) normal tolerance. Screening cost 59p per subject and 81 pounds per case detected. Of the 17 people with previously undiagnosed diabetes, eight were asymptomatic and 11 had not visited their general practitioner in the past three months. CONCLUSIONS: A postal request system for self testing for postprandial glycosuria in people aged 45-70 is a simple and effective method of population screening for diabetes mellitus. PMID- 1912919 TI - Coronary heart disease. PMID- 1912921 TI - ABC of vascular diseases. Varicose veins. PMID- 1912920 TI - Importance of obesity. PMID- 1912922 TI - Police surgeons and rape victims. PMID- 1912923 TI - 'Brittle' diabetes. PMID- 1912924 TI - Eating disorders in insulin dependent diabetes mellitus. PMID- 1912925 TI - Intravenous immunoglobulin and myalgic encephalomyelitis. PMID- 1912926 TI - Controlled trials in single subjects. PMID- 1912927 TI - Cervical samplers. PMID- 1912928 TI - Waiting for coronary angioplasty. PMID- 1912929 TI - Cervical screening and the new contract. PMID- 1912930 TI - Vitamin D deficiency in elderly people. PMID- 1912931 TI - Condyloma acuminata and risk of cancer. PMID- 1912932 TI - The mysterious 'urethral syndrome'. PMID- 1912933 TI - Assault after ingestion of antidepressant. PMID- 1912934 TI - Requests for organ donation. PMID- 1912935 TI - Tattoos. PMID- 1912936 TI - Undergraduate medical education. PMID- 1912937 TI - In memoriam to Daniel Sandoz. PMID- 1912938 TI - The Balbiani ring 6 induction in Chironomus. AB - Balbiani ring (BR) genes in polytene chromosomes of Chironomus salivary glands code for secretory proteins of the sp-I family, 10(6) D. They are used by the aquatic larva to spin a housing and feeding tube. The expression of the BR gene family undergoes correlated changes depending on the environment. In the presence of certain sugars, ethanol or glycerol the normally most active BR2 regresses and its products disappear. There is a parallel induction of a new BR, BR6, and a new sp-I protein. The change seems to represent an adaptative response to phosphate depletion in the larval haemolymph produced by the inducing agents. The BR2 (and BR1) products are heavily phosphorylated and the BR6 product non-phosphorylated. One of the BR2-coded sp-I proteins is cleaved off close to the C-terminus and material with properties expected of the resulting polypeptide can be recovered in the nuclei, accumulating in the BR. This might represent a feed-back signal from translation to transcription. PMID- 1912939 TI - Cholesteric liquid crystalline DNA; a comparative analysis of cryofixation methods. AB - The ultrastructure of liquid crystalline phases of DNA raises numerous problems because of the structure itself which is fluid and which nature depends on the relative amount of DNA, water and ions. Different cryofixation methods were tested and compared after freeze-fracture of the specimen. A good ultrastructural preservation of the samples can be achieved without addition of any cryoprotectant by quick-freezing against a copper block cooled down to liquid helium temperature. Then, molecular orientations can be followed very accurately and the local disorder around a mean direction which exists in the liquid state is kept in the frozen structure. PMID- 1912940 TI - Sites of transcription of adenovirus type 5 genomes in relation to early viral DNA replication in infected HeLa cells. A high resolution in situ hybridization and autoradiographical study. AB - The distribution of viral RNA molecules in HeLa cells infected with adenovirus type 5 (Ad5) was determined by in situ hybridization at the ultrastructural level at an intermediate stage of nuclear transformation, when viral DNA synthetic activities were maximal but progeny viruses were still sparse. Transcription sites of the viral DNA were localized by short pulse, high resolution autoradiography. Nascent viral RNA was found mainly within the nuclear compartment identified at the peripheral replicative zone, which is known to be the main replicative site of Ad5 viral genomes. Viral RNA molecules also were present, but to a markedly lesser extent, within the contiguous single-stranded (ss) DNA accumulation site, another intranuclear virus-induced structure in which some replication of viral genomes also occurs. Two other virus-induced nuclear structures contained viral RNA, the occasional exceptionally enlarged clusters of interchromatin granules and the compact rings, both DNA-free structures of unknown significance but which might play a role in the process of maturation of the Ad5 primary transcripts. Viral messenger RNA molecules were localized over the large areas of the cytoplasm which contain numerous ribosomes. Our analysis of the effects of various enzymatic pretreatments of the sections of infected cells on the revelation of nascent RNA by in situ hybridization is reviewed. PMID- 1912941 TI - Cellular interactions and tubulin detyrosination in fibroblastic and epithelial cells. AB - In mammalian cells most microtubules are enriched in tyrosinated alpha-tubulin (tyr-tubulin). Other subclasses of microtubules are present in variable amounts and some are enriched in detyrosinated alpha-tubulin (glu-tubulin). We examined the effect of cell-cell interactions on the level of glu-tubulin in microtubules. This was studied by quantitative immunofluorescence using antibodies against tyr- and glu-tubulin. We found that in cells which have established cell-cell contacts, the ratio of glu-/tyr-tubulin is higher than in isolated cells. We also examined the effect of cell-cell interactions on the glu-/tyr-tubulin ratio by using the antibody blocking method of Schulze and Kirschner [42]. Microtubules containing mainly tyr-tubulin had been blocked first by a polyclonal antibody against tyr-tubulin and several layers of secondary antibodies. The unblocked microtubules were then labeled by a monoclonal antibody against alpha-tubulin. Since the coating efficiency of microtubules by the anti-tyr tubulin depends on the amount of tyr-tubulin in each microtubule, this procedure allows the visualization of microtubules enriched or depleted in tyr-tubulin in specific domains of each cell. Microtubules were more extensively blocked in subconfluent than in confluent cells and preferentially at the periphery of the cytoplasm. In cells present at the margin of an artificial wound produced in a confluent monolayer, the amount of blocked microtubules increased slowly with time (between 2 and 4 h). These results are consistent with the hypothesis that cell-cell contacts lead to increased tubulin dytyrosination both in fibroblastic and epithelial cells. PMID- 1912942 TI - New data on the microtubule surface lattice. AB - The in vitro polymerisation of tubulin is a remarkable example of protein self assembly in that several closely related microtubule structures coexist on the polymerisation plateau. Unfixed and unstained in vitro assembled microtubules were observed in vitreous ice by cryo-electron microscopy. New results are reported that considerably extend previous observations [47]. In ice, microtubule images have a distinctive contrast related to the number and skew of the protofilaments. The microtubules observed have from twelve to seventeen protofilaments. Comparison with thin sections of pelleted material allows a direct identification of images from microtubules with thirteen, fourteen and fifteen protofilaments. A surface lattice accommodation mechanism, previously proposed to explain how variable numbers of protofilaments can be incorporated into the basic thirteen protofilament structure, is described in detail. Our new experimental results are shown to be in overall agreement with the theoretical predictions. Only thirteen protofilament microtubules have unskewed protofilaments, this was confirmed by observations on axoneme fragments. The results imply that the microtubule surface lattice is based on a mixed packing which combines features of the standard A and B lattices. PMID- 1912943 TI - Dynamic image analysis applied to the study of ciliary beat on cultured ciliated epithelial cells from rabbit trachea. AB - We have developed an automated image analysis method to study the ciliary beat frequency of ciliated cells of the primary culture from rabbit trachea. The ciliated outgrowth image is digitized and the variation in optical density is automatically calculated for each selected area of interest. 32 measurements of ciliary beat frequency are, in this way, calculated simultaneously in 6 min. With this reliable device, some studies on baseline frequency of control culture have been carried out. There was no variation in the mean frequencies of ciliated cells of the primary culture of different tracheas in our culture conditions. Moreover, the values of ciliary beat frequency at the starting point of the outgrowth were similar to those at the periphery of the outgrowth. There is nevertheless a slow decrease in frequencies versus the duration of culture. We have also established that the frequency of ciliary beat of some cells fluctuates in a periodic pattern whereas the majority of the ciliated population beat in a stable way. The image analysis process allows us to perform a cartography of frequencies on the video display. It also allows us to have access to the frequency of one cilium. Our method therefore seems to be reliable and furthermore simple in the evaluation of the potential effect of inhaled toxic compounds on ciliated cells of mammalian respiratory tract. PMID- 1912944 TI - An helicoidal structure surrounding the cilium axoneme: visualization by the monoclonal antibody CC-248. AB - Monoclonal antibody CC-248 labels cilia differentially on Triton X-100 permeabilized ciliated epithelium of quail oviduct by indirect immunofluorescence. On isolated ciliated cells, a punctuated staining is seen at the distal region over the bend of cilia. Electron micrographs of immunoperoxidase and immunogold techniques showed that the punctuated fluorescence corresponds to a helical disposition of CC-248 antigenic sites. This labeling was arranged on the axonemal distal region either as a simple or a double helix externally disposed around the nine microtubular doublets. These results suggest the existence of a detergent insoluble structure in the ciliary matrix that might concern the ciliary skeleton, probably acting as an elastic recoil that keeps the structural integrity of the axoneme during bending. The cross-reactivity of CC-248 MAb with the intermediate filament cytoskeleton of ciliated and smooth muscle cells indicates that this structure might be related to the intermediate filament family. PMID- 1912945 TI - Spermatozoa and relationships in Palaeognath birds. AB - In this paper the authors describe the ultrastructure of the mature spermatozoon and the spermatid in Struthio camelus and Dromaius novaehollandiae. The first species is characterized by a rod-like perforatorium within an endonuclear canal in the anterior third of the nucleus, while the second is characterized by an extremely reduced completely extranuclear perforatorium. Other differences are in the sperm dimensions, the number of mitochondria and the length of the axonemal accessory fibers. Considering both the present data and previous findings, Palaeognath birds appear to be a peculiar and monophyletic group, characterized by: 1), a conical acrosome surrounding the nucleus; 2), a fibrous sheath around most of the axoneme; and 3), an elongated distal centriole occupying the entire midpiece. Within this group, Tinamiformes seem to be more primitive than Struthioniformes. In the latter order Dromaius is distinctly different from the reduced Struthio and Rhea which are closely related to one another by the presence of a rod-like endonuclear perforatorium. PMID- 1912946 TI - Brefeldin A induces a microtubule-dependent fusion of galactosyltransferase containing vesicles with the rough endoplasmic reticulum. AB - The fungal drug brefeldin A (BFA) has recently been found to induce a redistribution of medial- and cis-Golgi components to the endoplasmic reticulum (ER), raising the possibility of the existence of a retrograde pathway from the Golgi complex to the ER. Here, we demonstrate a BFA-induced reversible rearrangement of the trans-Golgi membrane protein galactosyltransferase (Gal-T) to the ER in HeLa cells. With immunofluorescence microscopy we have shown that BFA first caused a rapid change of Gal-T immunolabelling from a normal Golgi complex pattern to long and slender structures emanating from the cell centre and co-localizing with tubulin. Then immunofluorescence became ER-like. This effect was not dependent on ongoing protein synthesis and was reversed to normal within 120 min after removal of the drug. Restoration of the Golgi complex after removal of brefeldin A was energy-dependent but not mediated by microtubules nor dependent on protein synthesis. BFA-induced backflow of Gal-T was inhibited by nocodazole, a microtubule-disrupting agent. Immunoelectron microscopy showed that BFA treatment resulted in the fusion of Gal-T-containing vesicles with the ER. Furthermore, sucrose gradient centrifugation showed a significant shift in density of mature Gal-T polypeptides upon BFA treatment: about 40% of the enzyme migrated from its original density (1.13 g/ml) to the density of rough ER (1.19 g/ml). Thus, BFA caused microtubule-dependent vesicular backflow from a trans Golgi component to the ER followed by fusion of the Golgi-derived vesicles with the ER. PMID- 1912947 TI - Neurosteroids: a new function in the brain. AB - "Neurosteroids" accumulate in the central nervous system independently of supply by peripheral endocrine glands. Dehydroepiandrosterone (DHA) and pregnenolone (delta 5P) were first found in the rat brain. Then, a steroid biosynthetic pathway was demonstrated in oligodendrocytes, mostly by enzyme immunocytochemistry and biochemical studies in primary cultures of glial cells, where the formation, from appropriate radioactive precursors, of delta 5P, delta 5-pregn-3 beta, 20 alpha-diol (20 alpha-DH delta 5P), progesterone (P), 5 alpha pregnane-3,20-dione (5 alpha-DHP) and 3 alpha-hydroxy-5 alpha-pregnane-20-one (3 alpha, 5 alpha-THP), as well as estrogen-induced nuclear progesterone receptor (PR) was observed. Several biological effects of neurosteroids have been observed, such as electrical stimulation of neurones, involvement in behaviorial activities, modulation of GABAA-receptor (GABAA-R) function (potentiated by 3 alpha, 5 alpha-THP and its 21-hydroxyderivative, antagonized by delta 5P- and DHA sulfates) and growth/differentiation of glial cells in vitro. Preliminary findings suggest that the neurosteroid concept applies to all mammalian species, including man. Further investigations should assess the pathophysiological significance of the synthesis of neurosteroids and decipher their mechanisms of action via nuclear and membrane receptors. PMID- 1912948 TI - Mitochondrial maturation during neuronal differentiation in vivo and in vitro. AB - The evolution of the mitochondrion has been followed within differentiating neuronal cells, both in primary cultures of neurons from fetal rat cortex and during rat brain cortex maturation. Changes in total mitochondrial proteins (mt proteins) were evaluated, and qualitative changes in the mt-proteins pattern were analyzed using the Western blot technique. The evolution of mt-protein contents in cultured neurons resembles what is observed during rat brain maturation. The mitochondrion exhibits pronounced changes in the course of neurogenesis, in particular, bursts of mitochondrial masses accompanying the successive steps of neurogenesis are observed. There are indications that protein equipment of mitochondria during neuronal development undergoes variations. Although more work is required to establish the significance of these correlations, the present data might suggest an important role of the mitochondrion in neurogenesis. PMID- 1912949 TI - Mitochondrial biogenesis in rabbit articular chondrocytes transferred to culture. AB - The effect of the switch to aerobic growth conditions was examined in rabbit articular chondrocytes transferred to culture. Spectroscopic analysis of the cytochromes of the respiratory chain shows that only cytochrome b is present in chondrocytes from cartilage, cytochromes c, c1, and a.a3 being undetectable as compared with the typical spectrum found in a primary cell culture on day 4. Steady state levels of RNA transcripts of nuclear (cytochrome c) and mitochondrial genes (cytochrome b and cytochrome oxidase subunits II and III) involved in the oxidative metabolism were determined relative to the RNA transcripts of the nuclear gene for glyceraldehyde phosphate dehydrogenase involved in the glycolytic pathway and to mitochondrial ribosomal RNAs. Chondrocytes transferred to culture showed a general increase in the levels of all transcripts, but the effect on mitochondrial transcripts was much greater (x 20) than the effect on nuclear transcripts (x 3-4). These results show the absence of a coordinate regulation of the expression of mitochondrial and nuclear genes coding for components of the respiratory chain. The increase in mitochondrial DNA triggered by culture conditions does not appear to be sufficient to account for the enhanced transcription. Concomitant with these mitochondrial changes, the level of transcripts for the collagen II gene involved in the differentiation function decreases dramatically (3% of the control on day 3). PMID- 1912951 TI - Eosinophil granulocytopoiesis in hepatic periovular granulomas during the chronic phase of experimental murine Schistosomiasis mansoni. AB - We have observed in hepatic periovular granulomas of C3H mice infected with Schistosoma mansoni, in the chronic phase of the disease (12-19 weeks of infection), groups of early precursors and immature eosinophil granulocytes corresponding, at the ultrastructural level, to promyelocytes and myelocytes. Mitosis was also seen in eosinophil myelocytes. These eosinophil myeloid foci were observed in close contact with macrophages and epithelioid cells, and they were surrounded by an extracellular matrix, rich in collagen fibres. These morphological observations give support to the concept of a peripheral proliferation of eosinophils in chronic schistosomiasis, mediated by a factor secreted by macrophages present in granulomas. PMID- 1912950 TI - Precursors of neuropeptides in the marine worm Nereis diversicolor. In vitro translation of a precursor related to human prepro-cholecystokinin and immunolocalization of this precursor in the nervous system. AB - Total mRNA extracted from the brain of a marine worm, Nereis diversicolor, were in vitro translated using 2 cell-free systems: rabbit reticulocyte lysate and wheat germ extract. Among numerous products newly translated in both systems, only one class of 70 kDa polypeptides immunoprecipitated when we used a mixture of 3 well defined antibodies raised against known sequences of the human prepro CCK. At the cellular level, using immunocytochemistry techniques, strong and moderate immunoreactivities were seen in perikarya located in various ganglionic nuclei of the worm brain. Immunoreactive nerve fibres were visible in the neuropile but not in the infracerebral region, a neurohemal area. Immunoreactions also appeared on perikarya located in the anterior and medial groups of the ventral nerve cord. Furthermore, immunolabeled cells were observed in the midgut. Interestingly, several co-localizations of materials immunologically related to human prepro-CCK and CCK/gastrin were observed in the brain and the ventral nerve cord both in perikarya and in nerve fibres. We propose that, in Nereis a polypeptide (molecular mass 70 kDa) is the large precursor of molecules related to those of the CCK/gastrin peptide family. PMID- 1912952 TI - Strategies to prevent or control infections after bone marrow transplants. AB - Patients receiving bone marrow transplants are at risk of life-threatening infections early post-transplant. This predisposition results from extensive mucosal damage and severe granulocytopenia. Common causes of infection include bacteria and fungi. Infections with opportunistic pathogens occur later and are associated with defects in cellular and/or humoral immunity. The most common sites of infections are the gastrointestinal tract, oropharynx, lung, skin and indwelling vascular catheters. Empiric approaches designed to treat common bacterial and fungal pathogens are generally effective as are measures designed to prevent dissemination of infections. These approaches are also used to prevent fungal infections. PMID- 1912953 TI - Role of splenectomy in incidence and severity of acute graft-versus-host disease: a multicenter study of 157 patients. AB - Allogeneic bone marrow transplantation is a therapeutic option for many hematological malignancies. Graft-versus-host disease (GVHD) remains one of the major complications and has a high mortality rate. The pathophysiological mechanisms involved are poorly understood and GVHD prevention regimens still give disappointing results. This study concerned 157 patients with diverse diagnoses from Bordeaux, Grenoble and Marseille who had undergone an HLA-matched transplantation without T cell depletion. Thirty-one patients (20%) had been splenectomized before transplantation. The role of splenectomy in the incidence and severity of acute GVHD was investigated using a univariate and multivariate analysis of 11 risk factors including splenectomy. Univariate analysis found three significant risk factors linked with GVHD incidence: splenectomy, age of recipient and GVHD prevention by monotherapy versus a combination of methotrexate plus cyclosporin. Multivariate analysis retained only the effects of age and GVHD prevention on GVHD incidence and showed that splenectomy was the most important factor in GVHD severity. One explanation for the role of splenectomy could be the spleen's possible function as a filter of activated T lymphocytes from the transplant. We therefore concluded that it would be preferable to abstain from splenectomizing patients before transplantation although splenectomy is still advisable in certain malignancies after transplantation. PMID- 1912955 TI - Cytotoxic T lymphocyte precursor (CTL-p) frequency analysis in unrelated donor bone marrow transplantation: two case studies. AB - HLA 'matched' unrelated donor bone marrow transplantation (BMT) is associated with an increased incidence and severity of acute graft-versus-host disease (GVHD) in comparison with HLA-identical sibling transplants. Using a limiting dilution analysis system for quantitating frequencies of alloreactive cytotoxic T lymphocyte precursors (CTL-p), we previously demonstrated a correlation between CTL-p frequency and HLA disparity between responder and stimulator, and between CTL-p frequency and the incidence of acute GVHD following HLA A, B, DR matched unrelated donor BMT. In this study we assayed CTL-p frequencies in two HLA 'matched' unrelated donor/patient pairs, with single HLA antigenic mismatches detected by allogenotyping or isoelectric focusing but not by HLA serology, and demonstrated that the CTL-ps were specifically directed at the mismatched antigen. Both class I and class II antigens were detected. These data, and our previous work, suggest that high CTL-p frequencies in HLA 'matched' unrelated pairs are indicative of HLA antigenic variants undetected by serology but recognized by molecular typing, and that these are responsible for the value of the assay in predicting acute GVHD after BMT. We propose that this assay system be used in aiding final donor selection before unrelated or mismatched related donor BMT. PMID- 1912954 TI - Involved field radiation, fractionated total body irradiation, high dose cyclophosphamide, and autologous bone marrow transplantation in the treatment of malignant lymphomas. AB - We report the results of intensive therapy and autologous bone marrow transplantation (BMT) in 23 patients with malignant lymphoma (eight Hodgkin's disease and 15 non-Hodgkin's lymphoma) who failed primary therapy. All patients had evidence of disease prior to transplant therapy: 10 had never achieved a complete remission and 13 were in relapse. The preparative regimen included involved field radiation followed by fractionated total body irradiation and high dose cyclophosphamide. A complete remission was achieved in 15 patients, 11 of whom continue in unmaintained complete remission from 27 to 72 months after BMT (median follow-up of 52 months). Of the remaining patients, five did not achieve a complete remission and three died of early toxicity. The event-free survival of the entire group is 47%. Disease status at the time of BMT was significantly correlated with patient outcome. The event-free survival of 13 patients in whom there was no objective evidence of tumor growth on conventional dose therapy was 77% compared with only 10% in patients with tumors progressing on conventional dose therapy (p less than 0.002). All six patients transplanted in untreated relapse continue in unmaintained remission, suggesting that debulking chemotherapy may not be necessary before BMT. Alternative approaches are needed in patients whose tumors progress on conventional dose therapy. PMID- 1912956 TI - Disappearance of minimal residual lymphoblastic leukemia cells 6 months after allogeneic bone marrow transplantation without GVHD. AB - The recent development of the polymerase chain reaction (PCR) has enabled us to determine the hypervariable sequence of immunoglobulin heavy chain known as complementarity determining region (CDR)-III. We amplified the leukemia-specific CDR-III from common acute lymphoblastic leukemia (cALL) cells using the PCR and determined its sequence. To detect minimal residual leukemia (MRL) cells, a second round PCR was performed with clone-specific primers corresponding to 5' and 3' ends of CDR-III to detect MRL cells. A million-fold diluted leukemia cells were clearly detected. Using stepwise diluted materials, the number of residual cells was semiquantitatively estimated. In one patient with cALL, induction chemotherapy resulted in a hematologically complete remission with only a 2-log reduction of the leukemia cells. MRL cells at a level of 10(-6) were also detected within 1 month after bone marrow transplantation (BMT), but leukemia cells were not detectable 6 months after BMT. PMID- 1912957 TI - Multicenter trials versus observational databases. PMID- 1912958 TI - Possible prevention of Pneumocystis carinii pneumonia by pentamidine aerosol after bone marrow transplantation. PMID- 1912959 TI - Arthritis in the elderly. PMID- 1912960 TI - Immune markers in vasculitis. AB - Systemic vasculitides are a group of autoimmune diseases associated with intense leucocytic vascular infiltrates and the presence in the serum of autoantibodies to neutrophil enzymes. This article discusses the significance of these and other immune markers for the diagnosis and monitoring of patients with vasculitis, as well as their possible pathogenic consequences. PMID- 1912961 TI - An introduction to decompression illness. AB - Decompression illness was formerly an occupational hazard confined to professional divers and compressed-air workers. With the increasing popularity of recreational diving it has come to involve a wider cross-section of the population. Furthermore, the proportion of cases presenting with the more serious manifestations of the disease appears to be rising. PMID- 1912962 TI - Enteral nutrition in childhood. AB - The frequency with which malnutrition may complicate chronic illness in children has been belatedly recognized, as has the role that nutritional support may play, either as primary treatment or in the management of disease- or treatment-related malnutrition. Consequently, enteral nutrition is increasingly used in the management of sick children. PMID- 1912963 TI - DC cardioversion. AB - DC cardioversion is a safe, simple procedure for the management of patients with tachyarrhythmias. Its great advantages in an emergency are its immediate effect and the avoidance of the potential side effects of drug therapy. It should be considered in the management of any patient with a tachyarrhythmia. PMID- 1912964 TI - Geographical skull. PMID- 1912965 TI - MRCPsych. Part Two: The oral examination. PMID- 1912966 TI - Children and smoking. PMID- 1912967 TI - Thrombolysis for peripheral arterial occlusion. PMID- 1912968 TI - Surgical wards and progressive patient care: new challenges. PMID- 1912969 TI - Organizational implications of hospital information systems. PMID- 1912970 TI - Disagreement over the appropriate use of X-rays. PMID- 1912971 TI - Patient dose monitoring: the first step in radiation control. PMID- 1912972 TI - The inflammatory response in asthma. AB - This article reviews current evidence concerning the pathological basis of asthma and the inflammatory mechanisms involved. Findings from postmortem and bronchoscopy studies are used to discuss the characteristics of inflamed airways and the roles played by various inflammatory cells. Possible long-term sequelae and the implications for treatment are also reviewed. PMID- 1912973 TI - Entrapment neuropathies: 1. Upper limb. AB - Accurate diagnosis of nerve entrapment requires a sound knowledge of anatomy and careful examination of the patient. Diagnosis is aided by specific clinical tests and neurophysiological investigation. This article reviews clinical presentation, relevant anatomical detail and appropriate investigations in the management of entrapment neuropathies of the upper limb. PMID- 1912974 TI - Entrapment neuropathies: 2. Lower limb. AB - Entrapment neuropathy is a form of compression neuropathy (see previous article). It is rare in the lower limb. Fibular tunnel syndrome, meralgia paraesthetica and tarsal tunnel syndrome are reviewed here. PMID- 1912975 TI - Human, pig and guinea-pig bladder smooth muscle cells generate similar inward currents in response to purinoceptor activation. AB - The contribution of purinergic neurotransmission to bladder excitation in pigs and man is small. Exogenously-applied adenosine-trisphosphate (ATP) however, elicits large inward currents in dispersed bladder smooth muscle cells in both species. The essential properties of the ATP-induced current in human and pig detrusor are similar and the current intensity is comparable to those in the guinea-pig, which has a powerful purinergic excitatory innervation. This suggests that other features of the tissue such as the closeness of the innervation and the degree of cell-to-cell coupling may be important in determining the effectiveness of purinergic transmission. PMID- 1912977 TI - Characterization of a novel, hydrophilic dihydropyridine, NKY-722, as a Ca2+ antagonist in bovine cultured adrenal chromaffin cells. AB - 1. To characterize NKY-722, a novel hydrophilic dihydropyridine derivative, as a Ca2+ antagonist, we examined its effects on 45Ca2+ influx, intracellular free Ca2+ concentrations [( Ca2+]i), and release of noradrenaline and adrenaline in bovine cultured adrenal chromaffin cells. 2. NKY-722 had little effect on basal 45Ca2+ influx into the resting cells, but inhibited high K+ (35.9 mM)-evoked 45Ca2+ influx in a concentration-dependent manner with an IC50 value of 5.2 nM. 3. NKY-722 inhibited high K(+)-evoked increases in [Ca2+]i in a concentration dependent manner without effect on the resting [Ca2+]i. 4. NKY-722 had little effect on basal release of noradrenaline and adrenaline but inhibited high K(+) evoked release of noradrenaline and adrenaline in a concentration-dependent manner with IC50 values of 5.0 nM and 4.8 nM, respectively. 5. Nicardipine, a prototype of NKY-722, also inhibited high K(+)-evoked 45Ca2+ influx and release of noradrenaline and adrenaline in a concentration-dependent manner: the IC50 value for high K(+)-evoked 45Ca2+ influx was 51 nM, and the values for high K(+) evoked release of noradrenaline and adrenaline were 52 nM and 50 nM, respectively. 6. These results show that NKY-722 is a hydrophilic Ca2+ antagonist ten times more potent than nicardipine. PMID- 1912976 TI - Mechanisms controlling caffeine-induced relaxation of coronary artery of the pig. AB - 1. We studied the effects of caffeine on coronary artery smooth muscle of the pig by measuring changes in isometric tension, cytosolic free Ca(2+) concentration ( [Ca2+]i) and transmembrane potential. 2. In the absence of tone, caffeine induced a concentration-dependent transient contraction of coronary artery strips, followed by sustained relaxation. Simultaneously with the relaxation, caffeine, 25 mM, hyperpolarized the smooth muscle cells by 7.7 +/- 0.9 mV. 3. Caffeine caused a concentration-dependent relaxation of strips precontracted with 10(-5)M acetylcholine (ACH). A supramaximal relaxing concentration of 25 mM caffeine produced an additional transient increase in [Ca2+]i on the Ca2+ plateau of ACh tonic contraction, which was followed by a decrease in [Ca2+]i to a level slightly below the basal concentration. This relaxation was accompanied by a hyperpolarization of 7.3 +/- 0.9 mV. 4. KCI 120 mM (high K+) contracted the strips with a concomitant depolarization of 38.6 +/- 1.6 mV and sustained increase in [Ca2+]i. Caffeine caused a concentration-dependent relaxation of high K+-induced contraction. Caffeine, 25 mM, decreased the Ca2+ plateau to a level that remained above the basal concentration of Ca2+ but did not change the membrane potential. 5. When strips were placed in a Ca(2+)-free medium with EGTA 2mM, and, in addition, ACh was applied successively three times, both intracellular and extracellular mobilizable Ca2+ pools were depleted. In these conditions, phorbol 12,13 dibutyrate (PDBu) 10(-7) M and prostaglandin F 2 alpha (PGF 2 alpha) 10(-5) M contracted the strips. Caffeine (25 mM) inhibited these contractions with no change in [Ca2+]i. 6. Forskolin, 3 x 10 -7M, inhibited ACh induced-contraction but did not affect those induced by PDBu. 7. In conclusion, these results show that caffeine has multiple cellular effects. During caffeine induced relaxation, [Ca2" Ii, adenosine 3': 5'-cyclic monophosphate (cyclic AMP) content and membrane potential are modified. The findings suggest, however, that these effects are secondary, and that caffeine acts mainly by another unknown mechanism, possibly involving a direct inhibition of the contractile apparatus. PMID- 1912978 TI - Haemodynamic changes and acetylcholine-induced hypotensive responses after NG nitro-L-arginine methyl ester in rats and cats. AB - 1. The haemodynamic effects of NG-nitro-L-arginine methylester (L-NAME; 1, 3, 10 and 30 mg kg-1) and its potential ability to attenuate the hypotensive responses to acetylcholine (0.03, 0.1, 1.0 and 3.0 micrograms kg-1) have been investigated in anaesthetized rats and cats. 2. In the rat, L-NAME elicited a dose-dependent pressor effect increasing mean arterial blood pressure from the baseline value of 116 +/- 4 mmHg to a maximum of 156 +/- 6 mmHg with 30 mg kg-1. This increase in blood pressure could be only partly reversed by L-arginine (300 mg kg-1). However, the increase in blood pressure by lower doses (up to 10 mg kg-1) of L NAME was effectively reversed by L-arginine (1000 mg kg-1). 3. In the cat, L-NAME did not significantly modify systemic haemodynamic variables (heart rate, mean arterial blood pressure, cardiac output, stroke volume or total peripheral resistance), when compared to the changes in saline-treated animals. Administration of L-arginine did not cause any significant effect in cats treated with L-NAME, but some decrease in heart rate and increases in cardiac output and stroke volume were observed in the saline-treated group. 4. With the lowest dose (1 mg kg-1), L-NAME did not affect tissue blood flows in the cat, but higher doses (3 and 30 mg kg-1) significantly reduced blood flows to the mesentery, stomach, spleen, intestines, lungs and the total liver. L-Arginine (300mgkg-1) injected into the control (saline-treated) animals resulted in a significant increase in blood flow to the heart, mesentery, lungs as well as the total liver, particularly its portal fraction. L-Arginine-induced increases in tissue blood flows (mesentery, kidneys, spleen, lungs, total liver and portal blood flow) in saline-treated animals were attenuated in animals treated with L-NAME.5. The acetylcholine-induced peak hypotensive response was not reduced in rats or cats by L-NAME. The duration of acetylcholine response was, however, attenuated in both species by L-NAME. Treatment with L-arginine (10-100mg kg- 1) did not change the acetylcholine-induced hypotension.6. The above results reveal a marked difference between the haemodynamic effects of L-NAME in rats and cats and suggest that in cats, unlike rats, the role of the L-arginine-NO pathway in the regulation of blood pressure is rather limited, although such a pathway may exist in several tissues. Furthermore, the hypotensive response to acetylcholine in both species seems to be mediated largely by NO-independent pathways. PMID- 1912979 TI - Nitroglycerin relaxes coronary artery of the pig with no change in glutathione content or glutathione S-transferase activity. AB - 1. The role of glutathione content and glutathione S-transferase activity in vascular relaxant responses to nitroglycerin was evaluated in potassium (30 mM) contracted coronary artery strips of the pig by measuring changes in tension, glutathione content and glutathione S-transferase activity. 2. Prior exposure of coronary artery strips to nitroglycerin (10(-5)M or 10(-4)M for 20 min) resulted in tachyphylaxis to subsequent relaxation to nitroglycerin (10(-8)-10(-5)M). 3. The glutathione content and glutathione S-transferase activity of the arterial strips rendered tachyphylactic by prior exposure to nitroglycerin (10(-5)M for 20 min or 10(-3)M for 120 min) were not significantly different from those of control strips. 4. Treatment with diethyl maleate (10(-4)M or 10(-3)M for 60 min) markedly depleted arterial glutathione content in a concentration-dependent manner with no change in glutathione S-transferase activity. 5. The relaxant response of coronary artery strips to nitroglycerin (10(-8)-10(-5)M) was completely unaffected following treatment with diethyl maleate (10(-4)M or 10( 3)M for 60 min). 6. The results suggest that vascular glutathione content does not play an important role in vascular relaxation or tolerance development to nitroglycerin, at least in pig isolated coronary artery. PMID- 1912980 TI - Blockade of intracellular actions of calcium may protect against ischaemic damage to the gerbil brain. AB - 1. The brain cytoprotective effects of a putative calcium-associated protein kinase inhibitor, HA1077, as well as a calcium entry blocker nicardipine were evaluated in models of cerebral ischaemia in Mongolian gerbils. Morphological changes characterizing delayed neuronal death of selectively vulnerable CA1 pyramidal neurones in the hippocampus of the Mongolian gerbil brain occurred 7 days after transient bilateral occlusion of the common carotid arteries. 2. A single injection of HA1077 (1 and 3 mg kg-1, i.p.) 5 min after the occlusion led to a dose-dependent protection of the CA1 neurones. Repeated administrations of HA1077 (1 and 3 mg kg-1, i.p., twice daily for 7 days post-ischaemia) revealed an increase in the number of normal cells, compared to findings with a single administration. 3. In contrast to HA1077, nicardipine (0.3 and 1 mg kg-1, i.p.) did not reduce neuronal degeneration. 4. HA1077 did not interact with the ion channel within which MK-801 binds, as determined by receptor binding. 5. The calcium ionophore, A23187, caused a tonic contraction in canine cerebral arterial strips. HA1077, but not nicardipine, relaxed the A23187-induced contraction, concentration-dependently. 6. These results suggest that blockade of the intracellular actions of calcium may provide protection against ischaemic damage in the brain. PMID- 1912981 TI - Inotropic and electrophysiological effects of BDF 9148, a congener of DPI 201 106, in guinea-pig atria and papillary muscles. AB - 1. BDF 9148 is a newly synthesized congener of DPI 201-106 in which the piperazidinyl moiety has been replaced by an azetidine-3-oxy-moiety. The inotropic effect of both drugs was studied as well as their influence on the action potential, by use of standard microelectrode techniques. 2. BDF 9148 increased the contractile force of guinea-pig atria and papillary muscles. The EC50 was 1.32 X 10(-7) mol l-1 and 0.7 X 10(-6) mol l-1 respectively. DPI 201-106 was effective in a similar concentration-range, the EC50 being 2.6 X 10(-7) mol l 1 for atria and 2.8 X 10(-7) mol l-1 for papillary muscles. 3. Both drugs caused a concentration-dependent prolongation of the relaxation time of the isometric contraction curve. With 10(-6) mol l-1 BDF 9148, the mean increase was 39.1 +/- 4.4 ms in atria and 39.4 +/- 7.5 ms in papillary muscles while 10(-6) mol l-1 DPI 201-106 caused increases of 56.7 +/- 2.5 ms and 79.3 +/- 11.7 ms, respectively. The effect of BDF 9148 was not prevented by propranolol, but was reversed by 3 X 10(-6) mol l-1 tetrodotoxin. Pretreatment of atria with 3 X 10(-8) mol l-1 BDF shifted the concentration-response curve of ouabain to the left and reduced the EC50 of the glycoside from 3.21 X 10(-7) mol l-1 to 2 X 10(-7) mol l-1. 4. BDF 9148 and DPI 201-106 concentration-dependently increased the action potential duration of papillary muscles and their functional refractory period. The drugs did not modify the resting potential, the action potential amplitude or the maximum depolarization velocity.5. All effects of BDF 9148 persisted after washout. The lipophilic drug accumulated in the tissues and the tissue drug concentration was little reduced by washout of BDF 9148 from the organ bath.6. In contrast to DPI 201-106, which had a prominent negative chronotropic effect in right atria, BDF 9148 caused only a slight reduction of the beating frequency with the largest (3 x 10 5mol 11) concentration.7. The results are consistent with BDF 9148 being a sodium channel activator with much weaker influence on the beating frequency than the parent compound DPI 201-106. PMID- 1912982 TI - Measurements of tacrine and monoamines in brain by in vivo microdialysis argue against release of monoamines by tacrine at therapeutic doses. AB - 1. The concentration of tacrine (tetrahydroaminoacridine or THA) in plasma, regions of brain and cerebral extracellular fluid has been studied in the rat at various times following injection of a dose of 5 mg kg-1, i.p. 2. The peak plasma THA concentration was 2.46 nmol ml-1, and occurred 30 min post injection and clearance was first order (t1/2 = 90 min). The concentration in the brain peaked between 30-60 min, and was around 30 times plasma concentration (striatum peak concentration = 65 +/- 3 nmol g-1). Extracellular cerebral concentration measured by in vivo microdialysis was similar to plasma concentration with the peak occurring 100 min post-injection. 3. No evidence was obtained by in vivo dialysis for THA inducing dopamine release from striatum or 5-hydroxytryptamine (5-HT) release from the frontal cortex. Enhanced release of dopamine did occur after (+) amphetamine (5 mg kg-1, i.p.) injection, while KCl (100 mM) in the probe released both dopamine and 5-HT. 4. Since the minimum plasma THA concentration achieved in this study was at least twice that found in the plasma of patients given THA for the treatment of dementia, these results suggest that monoamine release in the brain does not occur during therapy. PMID- 1912983 TI - A receptor that is highly specific for extracellular ATP in developing chick skeletal muscle in vitro. AB - 1. Extracellular adenosine 5'-triphosphate (ATP) activated an early excitatory conductance followed by a late potassium conductance in developing chick skeletal muscle. A series of ATP analogues were tested for their ability to activate these two conductances. All compounds tested were either agonists for both responses or for neither. Furthermore, the potency of agonists was similar for the two responses. 2. The order of potency for agonists was ATP approximately adenosine 5'-O-(3-thiotriphosphate) (ATP-gamma-S) approximately 2-methylthio-ATP (2-CH3S ATP) greater than 2'-deoxy-ATP approximately 3'-deoxy-ATP greater than adenosine 5'-tetraphosphate (ATP-OPO3) approximately adenosine 5'-diphosphate (ADP). Many other ATP analogues were not agonists. 3. Activation of the excitatory response did not require divalent cations. Furthermore, the concentration-response relation of the excitatory response was similar when ATP was applied as the free anion of ATP (ATP4-) or complexed with a divalent cation (M.ATP2-). 4. Three antagonists of the ATP response were characterized. 8-Br-ATP was a weak antagonist, while 2',3'-dialdehyde-ATP and DIDS (4,4'-diisocyanatostilbene-2,2' disulphonic acid) were potent irreversible inhibitors. The two conductances were equally affected by these antagonists. 5. These results suggest that both ATP responses are activated through the same receptor type, or two very similar receptors. PMID- 1912984 TI - Effect of NG-monomethyl L-arginine (L-NMMA) and NG-nitro L-arginine (L-NOARG) on non-adrenergic non-cholinergic relaxation in the circular muscle of the human ileum. AB - 1. We have investigated the effect of the NO synthesis inhibitors, NG-monomethyl L-arginine (L-NMMA) and NG-nitro L-arginine (L-NOARG) on the non-adrenergic non cholinergic (NANC) relaxation produced by electrical field stimulation in the circular muscle of the human ileum. 2. In the presence of atropine and guanethidine (1 and 3 microM, respectively), electrical field stimulation produced tetrodotoxin-sensitive relaxation of the strips. L-NMMA, starting from 100 microM, produced a concentration-dependent inhibition of the evoked relaxations (2Hz); maximal inhibition at 1 mM averaged about 35%. 3. The inhibitory effect of L-NMMA was unchanged by previous incubation with D-arginine while it was prevented by L-arginine (L-Arg). L-NMMA did not affect isoprenaline induced relaxation. 4. L-NOARG (1-30 microM) concentration-dependently inhibited the evoked relaxations at 2 Hz, up to a maximum of 65% inhibition, although in some strips complete inhibition of the response was observed. The effect of L NOARG was reversed by L-Arg. L-NOARG did not affect isoprenaline-induced relaxation. 5. These results suggest that NO may be involved in inhibitory NANC transmission in the circular muscle of the human ileum. PMID- 1912985 TI - Characterization of diadenosine tetraphosphate (Ap4A) binding sites in cultured chromaffin cells: evidence for a P2y site. AB - 1. Diadenosine tetraphosphate (Ap4A) a dinucleotide, which is stored in secretory granules, presents two types of high affinity binding sites in chromaffin cells. A Kd value of 8 +/- 0.65 x 10(-11) M and Bmax value of 5420 +/- 450 sites per cell were obtained for the high affinity binding site. A Kd value of 5.6 +/- 0.53 x 10(-9) M and a Bmax value close to 70,000 sites per cell were obtained for the second binding site with high affinity. 2. The diadenosine polyphosphates, Ap3A, Ap4A, Ap5A and Ap6A, displaced [3H]-Ap4A from the two binding sites, the Ki values being 1.0 nM, 0.013 nM, 0.013 nM and 0.013 nM for the very high affinity binding site and 0.5 microM, 0.13 microM, 0.062 microM and 0.75 microM for the second binding site. 3. The ATP analogues displaced [3H]-Ap4A with the potency order of the P2y receptors, adenosine 5'-O-(2 thiodiphosphate) (ADP-beta-S) greater than 5'-adenylyl imidodiphosphate (AMP-PNP) greater than alpha, beta methylene ATP (alpha, beta-MeATP), in both binding sites. The Ki values were respectively 0.075 nM, 0.2 nM and 0.75 nM for the very high affinity binding site and 0.125 microM, 0.5 microM and 0.9 microM for the second binding site. PMID- 1912986 TI - The effects of soman on the electrical properties and excitability of bullfrog sympathetic ganglion neurones. AB - 1. The effects of soman (0.1-10 microM), an irreversible inhibitor of acetylcholinesterase (AChE), were examined on the electrical properties of ganglion neurones of the paravertebral sympathetic chain of the bullfrog, Rana catesbeiana. 2. Soman (10 microM) depolarized 29 of 35 (83%) ganglion neurones studied by 6.4 +/- 0.65 mV within 10 min of application and reduced the cell input resistance in 9 of 11 neurones examined (82%) to 55 +/- 5.3% of control. 3. Soman (10 microM) significantly reduced the maximum amplitude and the maximum rate of rise of the action potential and the duration, but not the amplitude, of the after-hyperpolarization (AHP) following the action potential elicited by either direct or antidromic stimulation. The maximum rate of fall and the duration of the action potential were not significantly affected by soman. These actions of soman were independent of the agent-induced depolarization. When examined by a single microelectrode voltage clamp, soman reduced the amplitude and the time constant of the current underlying the slow AHP, IAHs. 4. Soman (1 10 microM) produced an increase in neuronal excitability which was evidenced as either an increase in the number of action potentials or a decrease in the interspike interval in response to constant-current depolarizing pulses. The soman-induced increase in excitability occurred independently of both the agent induced depolarization and the decrease in input resistance, was reversible with washing, was not caused by an inhibition of the M-current and was also recorded in dissociated sympathetic ganglion neurones.5. The effects of soman on the membrane potential, input resistance and the duration of the AHP but not cell excitability were blocked by pretreatment with atropine (10 microM). Pretreatment with dihydro-/J-erythroidine (DHbetalE) (10 microM) was ineffective in blocking or reversing the effects of soman. These results suggest that the direct actions of soman on the electrical properties of these neurones are mediated by activation of muscarinic receptors. PMID- 1912987 TI - In vitro vascular effects of cicletanine in pregnancy-induced hypertension. AB - 1. The vascular effects of cicletanine have been studied in vitro on ring preparations of inferior epigastric arteries from normotensive human females and human females with pregnancy-induced hypertension (preeclampsia). 2. Cicletanine (10(-7)-10(-3) M) elicited concentration-dependent relaxation of vessels precontracted with 10(-7) M noradrenaline (NA) or 60 mM K+ but was more potent in the former. Relaxation was significantly greater in rings from preeclamptic patients and was uninfluenced by endothelium removal. 3. The intracellular Ca dependent contractile responses to 10(-5) M NA in Ca-free medium as well as the subsequent extracellular Ca-dependent contractions (on restoration of external Ca) were significantly attenuated dose-dependently by cicletanine (10(-5) M, 3 x 10(-4) M) in arterial rings from both normotensive and preeclamptic patients. Cicletanine also relaxed rings precontracted by 25 mM K+ but was ineffective against 80 mM K(+)-induced contractions. 4. The inhibition of intracellular Ca dependent contractions was significantly greater in rings from preeclamptic than from normotensive patients whereas extracellular Ca-dependent contractions were comparably inhibited in both groups. Nifedipine, on the other hand, had little effect on the intracellular Ca-dependent contractions but significantly depressed extracellular Ca-dependent contractions. 5. Cicletanine-induced relaxation was uninfluenced by pretreatment with propranolol, ouabain, tetraethylammonium, procaine, indomethacin, cimetidine or tetrodotoxin but was antagonized by glibenclamide. 6. The results show that cicletanine inhibits contractile responses of human isolated inferior epigastric arteries by a mechanism unrelated to endothelial factors but associated with inhibition of calcium metabolism. An action of cicletanine on glibenclamide-sensitive K+ channels is also suggested. Cicletanine-induced inhibition was significantly greater in arteries from preclamptic patients. PMID- 1912988 TI - Possible dependence of pressor and heart rate effects of NG-nitro-L-arginine on autonomic nerve activity. AB - 1. The effects of NG-nitro-L-arginine (L-NNA) on mean arterial pressure (MAP) and heart rate (HR) were investigated in conscious rats. 2. Intravenous bolus cumulative doses of L-NNA (1-32 mg kg-1) dose-dependently increased MAP. Both mecamylamine and phentolamine increased MAP responses to L-NNA, angiotensin II and methoxamine. Propranolol, reserpine, atropine and captopril did not affect MAP response to L-NNA. 3. A significant negative correlation of HR and MAP responses to L-NNA was obtained in control rats but not in rats pretreated with reserpine or mecamylamine. Significant negative correlations also occurred in the presence of atropine, propranolol, phentolamine or captopril. 4. A single i.v. bolus dose of L-NNA (32 mg kg-1) raised MAP to a peak value of 53 +/- 3 mmHg and the effect lasted more than 2 h; the rise and recovery of MAP were accompanied by significant decrease and increase in HR, respectively. While both phentolamine and mecamylamine increased peak MAP response to L-NNA, mecamylamine abolished the biphasic HR response and phentolamine potentiated the bradycardiac component of HR. 5. Blockade of the autonomic nervous and renin-angiotensin systems did not attenuate the pressor effects of L-NNA. However, the biphasic HR response to L NNA is mediated via modulation of autonomic nerve activities. PMID- 1912989 TI - The effects of phosphoramidon on the regional haemodynamic responses to human proendothelin [1-38] in conscious rats. AB - 1. Cardiovascular responses to human proendothelin [1-38], in the absence and presence of phosphoramidon, were studied in conscious Long Evans rats, chronically instrumented for the continuous recording of heart rate, systemic arterial blood pressure and renal, mesenteric and hindquarters blood flows. 2. A dose of 0.1 nmol kg-1 human proendothelin [1-38] caused a slight pressor effect (maximum 5 +/- 2 mmHg), but a clear bradycardia (maximum -29 +/- 7 beats min-1). Renal haemodynamics were unchanged but there was mesenteric vasoconstriction and a vasodilation followed by a vasoconstriction in the hindquarters. 3. A dose of 1.0 nmol kg-1 human proendothelin [1-38] caused a gradual hypertension (maximum 42 +/- 4 mmHg at 10 min) and a profound bradycardia (-149 +/- 10 beats min-1 at 30 min). There were gradual but marked, renal and hindquarters vasoconstrictions, whereas there was a substantial mesenteric vasoconstriction that was relatively rapid in onset. 4. In 2 animals, administration of human proendothelin [1-38] at a dose of 10 nmol kg-1 caused an initial hypotension followed by a rapidly developing pressor effect; there were renal and mesenteric vasoconstrictions and vasodilatation followed by vasoconstriction in the hindquarters. These changes were very similar to those seen following injection of endothelin-1 (0.1 nmol kg 1). 5. Phosphoramidon (2 mumol kg-1) had no cardiovascular effects itself and it did not affect significantly the pressor or mesenteric vasoconstrictor effects of human proendothelin [1-38], but it reduced the bradycardia and renal and hindquarters vasoconstrictor responses. A higher dose of phosphoramidon (lOnmolkg ') caused significant attenuation of all the responses to human proendothelin [1 38], but a substantial mesenteric vasoconstrictor response still occurred under these conditions. 6 The results are consistent with the involvement of phosphoramidon-sensitive enzyme systems in the conversion of human proendothelin [1-38] to endothelin-1 in vivo. In addition, considering the different patterns of responses to human proendothelin [1-38] in the effector tissues studied (heart, and renal, mesenteric and hindquarters vascular beds), and the differential degrees of inhibition of them by phosphoramidon, it is likely that the effects of human proendothelin [1-38] were due to its local (rather than systemic) conversion to endothelin-1 by processes with differing degrees of susceptibility to phosphoramidon. PMID- 1912990 TI - Potencies of antagonists indicate that 5-HT1C receptors mediate 1 3(chlorophenyl)piperazine-induced hypophagia. AB - 1. 1-3(Chlorophenyl)piperazine (mCPP) (5 mg kg-1, i.p.) inhibited 2 h food intake in rats previously deprived of food for one day. Ten 5-hydroxytryptamine (5-HT) antagonists given s.c. opposed this hypophagic response. Calculated ID50 values correlated significantly with reported affinities (r = 0.81, n = 10, P less than 0.01) for 5-HT1C but not for 5-HT2, 5-HT1A, 5-HT1B or 5-HT1D receptors. 2. ID50 values of the ten antagonists against 5-hydroxytryptophan (5-HTP) + carbidopa induced head shakes (a 5-HT2-mediated response) correlated significantly (r = 0.81, n = 10, P less than 0.01) with their affinities for 5-HT2 but not for 5 HT1A, 5-HT1B, 5-HT1C or 5-HT1D receptors. 3. ID50 values for inhibition of hypophagia and head shakes did not correlate significantly with each other. 4. Ratios of ID50 values against hypophagia and 5-HT2-mediated head shakes gave indices of relative in vivo potencies independent of differences in drug metabolism and disposition. These ratios correlated highly significantly (r = 0.91, n = 10, P less than 0.001) with the ratios of the affinities of the drugs for 5-HT1C (but not for 5-HT1A, 5-HT1B or 5-HT1B or 5-HT1D receptors) and with their affinities for 5-HT2 receptors. These results strongly support the hypothesis that mediation of mCPP-induced hypophagia is by stimulation of 5-HT1C receptors and the mediation of 5-HTP-induced head twitches by 5-HT2 receptors. PMID- 1912991 TI - Barbiturates inhibit ATP-K+ channels and voltage-activated currents in CRI-G1 insulin-secreting cells. AB - 1. Patch-clamp recording techniques were used to examine the effects of barbiturates upon the ATP-K+ channel, and voltage-activated channels present in the plasma membrane of CRI-G1 insulin-secreting cells. 2. Thiopentone inhibited ATP-K+ channel activity when applied to cell-attached patches or the intracellular or extracellular surface of cell-free patches. Secobarbitone and pentobarbitone were also effective inhibitors of ATP-K+ channels in cell-free patches, whereas phenobarbitone was ineffective. 3. The diabetogenic agent, alloxan, which is structurally related to the barbiturates also produced an inhibition of ATP-K+ channel activity in outside-out patches. 4. Whole-cell ATP K+ currents were used to quantify the effects of the barbiturates: concentration inhibition curves for thiopentone, secobarbitone and pentobarbitone resulted in IC50 values of 62, 250 and 360 microM respectively. Phenobarbitone at a concentration of 1 mM was virtually ineffective. 5. Calculation of the apparent membrane concentrations for these drugs indicate that for a given degree of ATP K+ channel inhibition a similar concentration of each barbiturate is present in the membrane. This suggests that hydrophobicity plays a primary role in their mechanism of action. The pH-dependence and additive nature of barbiturate block also indicates a membrane site of action. 6. Thiopentone, (100 microM) was also found to inhibit differentially voltage-activated whole-cell currents. The relative potency of thiopentone at this concentration was 0.64, 0.38 and 0.12 for inhibiting Ca2+, K+ and Na+ currents respectively when compared with its ability to inhibit the ATP-K+ channel. PMID- 1912992 TI - The neuroprotective action of dizocilpine (MK-801) in the rat middle cerebral artery occlusion model of focal ischaemia. AB - 1. An acute model of focal ischaemia, which involves permanent occlusion of the middle cerebral artery of the rat with 4 h survival, was used to find the minimum effective plasma concentration of dizocilpine (MK-801) and to determine its dose effect relationship. 2. MK-801 was administered at the time of occlusion and was given as an i.v. bolus followed by an infusion for 4 h to maintain a steady state plasma concentration of the drug throughout the study. MK-801 was given at 3 dose levels; 0.04 mg kg-1 i.v. bolus + 0.6 micrograms kg-1 min-1 infusion; 0.12 mg kg 1 i.v. bolus + 1.8 micrograms kg-1 min-1 infusion; 0.4 mg kg-1 i.v. bolus + 6 micrograms kg-1 min-1 infusion, which gave mean plasma levels over the 4 h of 8.0 ng ml-1, 18.9 ng ml-1 and 113.2 ng ml-1 respectively. 3. MK-801 at 8.0 ng ml-1 gave 10% reduction in the volume of ischaemic brain damage in the cerebral cortex which just reached significance. The middle dose of MK-801 (18.9 ng ml-1) gave a highly significant reduction in the volume of ischaemic brain damage in the cerebral cortex and hemisphere, volumes of ischaemic tissue being reduced by 60% and 50% compared to saline-treated animals, respectively. The highest plasma concentration of MK-801 (113.2 ng ml-1) resulted in a 35% reduction in the volume of hemispheric damage and a 40% reduction in the volume of cortical damage, which were significant.4. The reduction in the amount of protection afforded by the highest dose of MK-801 may be due to the hypotensive effect of this dose. There was no protection against the volume of damage in the caudate nucleus for any of the doses of MK-801 tested.5. Therefore the minimum effective plasma concentration of MK-801 was 8.0 ngml1, although the greatest protection was seen with a plasma level of 18.9 ng ml- 1. This correlates well with the concentration of MK-801 required to block N-methyl-D-aspartate (NMDA) receptors and prevent NMDA receptor mediated neurotoxicity in vitro. PMID- 1912993 TI - Proceedings of the British Pharmacological Society meeting. University of Glasgow, 10-12 July, 1991. Abstracts. PMID- 1912994 TI - Outcome assessment in clinical trials of ankylosing spondylitis. PMID- 1912995 TI - Health service reforms and access to specialist services. PMID- 1912996 TI - Regenerative joint disease. PMID- 1912997 TI - Methods of assessment used in ankylosing spondylitis clinical trials: a review. AB - Twenty non-steroidal anti-inflammatory drug (NSAID) trials in ankylosing spondylitis (AS) were reviewed to assess the frequency with which statistically significant differences had been detected between active drug and either a placebo or an NSAID-free washout period. Differences in pain severity were almost invariability detected, irrespective of the scale employed. In contrast, significant differences in axial movement were rarely detected in placebo controlled studies, and only about half of the variables detected significant improvement with respect to a washout period. From our data it is difficult to differentiate whether the lack of difference with active therapy was due to inadequate sample size, non-responsive patients, or insensitive outcome measures. However, it is not surprising that between-drug differences are rarely detected in AS clinical trials of NSAIDs given our current inability to differentiate consistently an active treatment from a placebo and an active treatment phase from a washout period. PMID- 1912998 TI - The relationship of clinical and laboratory measurements to radiological change in ankylosing spondylitis. AB - Methods for scoring the severity of radiological change in patients with ankylosing spondylitis using plain X-rays of the sacroiliac (SI) joints and lumbar spine and computerized tomographic (CT) scans of the SI joints were evaluated in a cohort of 70 patients. Analysis of reproducibility was by the kappa statistic. Significant change over 12 months in a subgroup of patients was demonstrated by these scores. Ankylosis correlates negatively with erosions and sclerosis and the change in SI joint ankylosis correlates negatively with change in SI joint erosions as seen on CT scan. The clinical and laboratory correlates of these findings were examined. Pain, stiffness and sleep disturbance correlated positively with increasing SI joint sclerosis on CT scanning (r = 0.45; P less than 0.05) but negatively with ankylosis (r = -0.43; P less than 0.05). Orosomucoid levels predicted an increase in the radiological lumbar spine score. No other clinical or laboratory variable predicted radiological change. PMID- 1912999 TI - Does plasma exchange have any role in the treatment of systemic lupus erythematosus? PMID- 1913000 TI - Patients with ankylosing spondylitis show individual patterns of variation in disease activity. AB - Disease activity was monitored sequentially over 1 year in 22 patients with ankylosing spondylitis (AS) attending regularly the local NASS group. Assessments, using standard methods, were made at monthly intervals by the same observer. There was marked heterogeneity such that each patient's profile of disease activity was virtually unique. All patients experienced at least one exacerbation and most underwent exacerbations and remissions, reminiscent of the experience of many patients with rheumatoid arthritis. In most instances no reason for changes in disease activity could be discerned clinically. These observations raise the possibility that the natural history of disease in AS may be different for each individual patient, which, if true, would have important implications for the design of studies to test the efficacy of therapy and for approaches to investigating pathogenic mechanisms in patients with AS. PMID- 1913001 TI - A re-evaluation of the osteoarticular manifestations of psoriasis. AB - A distinctive peripheral arthropathy associated with psoriasis is well recognized, the classical pattern describing an asymmetrical oligoarthritis with predominant distal interphalangeal joint (DIP) involvement. There is some dispute about the frequency of this classical pattern and of the pattern of symmetrical polyarthritis resembling rheumatoid arthritis. Some of the dispute may be a result of loose definitions. In this clinical and scintigraphic study of 50 patients with psoriatic arthritis we have used tighter definitions of disease pattern and have found that 68% of this group had a symmetrical polyarthritis similar to that found in rheumatoid arthritis. Yet, arthritis associated with psoriasis differs from rheumatoid arthritis in a number of ways including the pattern of joint involvement, extra-articular osseous features, and radiological changes. Scintigraphic changes in psoriatic arthritis suggest that subclinical involvement of the manubriosternal and sternoclavicular joints is common, suggesting an association between psoriasis vulgaris and arthro-osteitis. A modified classification of the osteoarticular manifestations of psoriasis is proposed. PMID- 1913002 TI - Adult respiratory distress syndrome: an unrecognized premortem event in systemic lupus erythematosus. AB - A retrospective study of the medical records of 46 patients, comprising our SLE population over a 6-year period, noted that mortality (7 of 46:15.2%) was directly related to the adult respiratory distress syndrome. In five, a concomitant severe infection was detected. Overall, 17 of our 46 patients presented with infectious episodes. The only statistically significant factor predisposing to both infection and the adult respiratory distress syndrome was high dose corticosteroid administration. Our results suggest that adult respiratory distress syndrome is a clinical condition related to the death of lupus patients and commonly complicates infection. PMID- 1913003 TI - Prevalence of hypothyroidism in patients with polymyalgia rheumatica and giant cell arteritis. AB - The prevalence of thyroid disease and thyroid autoantibodies was evaluated in 367 patients with polymyalgia rheumatica (PMR) and/or giant cell arteritis (GCA). Thirty-seven patients had antibodies to thyroid microsomes or thyroglobulin; 18 had hypothyroidism requiring thyroxine replacement therapy. The prevalence of hypothyroidism (4.9%) was significantly greater than that found in 84 control subjects. PMID- 1913004 TI - Study designs and statistical methods in rheumatological journals: an international comparison. AB - In order to determine the characteristics of papers published in the rheumatological literature, we have conducted a survey of the seven leading rheumatological journals published in 1987; 1107 original papers have been reviewed and classified according to study design, statistical techniques, and country of origin. Almost half of the published papers were clinical descriptive studies without inferential power; both authors and editors should reflect whether the impact of these studies on the knowledge of readers justifies their frequency. Analytical research was represented mainly by randomized clinical trials (15.6%), and case control studies (14.2%). Cohort studies represented 5.4% and this seems a low figure in a specialty in need of more aetiological research. Almost half of the papers originated from the USA or the UK; journals edited in these countries published papers mainly from the same country. English language journals from other countries published a larger percentage of papers from other countries, including many non-English speaking nations. Bibliometric studies are desirable to evaluate trends in publication. PMID- 1913005 TI - In a patient with inflammatory arthritis and pitting oedema of the ankles, is there any indication for venography? PMID- 1913006 TI - Review of UK data on the rheumatic diseases--9. Scleroderma. PMID- 1913007 TI - Letter from America. PMID- 1913008 TI - Evening primrose oil in patients with rheumatoid arthritis and side-effects of non-steroidal anti-inflammatory drugs. AB - Forty patients with rheumatoid arthritis and upper gastrointestinal lesions due to non-steroidal anti-inflammatory drugs entered a prospective 6-month double blind placebo controlled study of dietary supplementation with gamma-linolenic acid 540 mg/day. Nineteen patients received active therapy (as evening primrose oil 6 g/day) and 21 received placebo (olive oil 6 g/day). No patient stopped non steroidal anti-inflammatory therapy but three patients in each group reduced their dose. Other results showed a significant reduction in morning stiffness with gamma-linolenic acid at 3 months and reduction in pain and articular index at 6 months with olive oil. Whilst gamma-linolenic acid may produce mild improvement in rheumatoid arthritis, olive oil may itself have hitherto unrecognized benefits. PMID- 1913009 TI - Venostasis, subclinical vasculitis and von Willebrand factor antigen. AB - Von Willebrand factor antigen (VW FAg) has been used as a marker for vasculitis and raised levels have been shown to correlate with active disease. The use of VW FAg levels in the diagnosis of vasculitic disorders has been proposed. However, certain cases of vasculitis have normal VW FAg levels and are difficult to diagnose; this is of importance because of the high mortality associated with these disorders. It has been suggested that venostatic stress can be used as a provocative test for stimulating VW FAg release, thereby improving the speed and sensitivity of diagnosis. We tested this hypothesis in a mixed group of 35 patients with vasculitis, systemic lupus erythematosus and rheumatoid arthritis and 16 controls. At baseline, although the levels were not outside the laboratory range, the disease groups had raised VW FAg compared with the simultaneously tested controls. Venostatic stress increased VW FAg activity in all disease groups, control levels also increased and differences between controls and disease groups diminished in significance. Therefore venostatic stress with VW FAg measurement does not produce a more sensitive test for vasculitis. Venostasis should be avoided when measuring VW FAg levels. PMID- 1913010 TI - Rapidly progressive aortic valve incompetence in a patient with rheumatoid arthritis. AB - A 27-year-old female with seropositive rheumatoid arthritis of onset at age 18 years developed progressive aortic valve incompetence requiring urgent aortic valve replacement. Rheumatoid aortic valve disease may be more rapidly progressive than aortic valve disease from other causes and awareness of this by the monitoring physicians may help to avoid the possible complications. PMID- 1913011 TI - Limited forms of Wegener's granulomatosis presenting as polymyalgia rheumatica. AB - The spectrum of Wegener's granulomatosis is broad, ranging from rapidly progressive disease to more indolent and limited forms. We report two cases with later onset disease who presented with polymyalgia rheumatica. Diagnosis of Wegener's was delayed but was ultimately aided by the demonstration of antineutrophil cytoplasmic antibodies. PMID- 1913012 TI - Sciatica caused by isolated non-Hodgkin's lymphoma of the spinal epidural space: a report of two cases. AB - Two patients are described in whom sciatica was caused by non-Hodgkin's lymphoma involving the spinal epidural space. Systematic investigation revealed no evidence of lymphoma in other sites. PMID- 1913013 TI - Antibodies to Proteus in rheumatoid arthritis. PMID- 1913014 TI - Analogue pain scores. PMID- 1913015 TI - Delayed diagnosis of systemic lupus erythematosus associated pulmonary hypertension. PMID- 1913016 TI - Hairy cell leukaemia and rheumatoid arthritis. PMID- 1913017 TI - Neurosensory adverse effects after combined phenylbutazone and misoprostol. PMID- 1913018 TI - Arrhythmia after pulse methylprednisolone therapy. PMID- 1913019 TI - Relationship between rheumatological diseases of man, pet dogs and their viruses. PMID- 1913020 TI - Treatment of polymyalgia rheumatica: lower initial dose. PMID- 1913021 TI - Bilateral septic arthritis of the hips complicating the arthropathy of haemochromatosis. PMID- 1913022 TI - Inefficacy of topical alpha interferon in the treatment of oral ulcers of Behcet's syndrome: a randomized, double blind trial. PMID- 1913023 TI - Biomechanical implications of mild leg length inequality. AB - The effect of mild leg length inequality (lower extremity length difference less than 3 cm) on posture and gait has been the source of much controversy. Many opinions have been expressed both for and against the need for intervention to reduce the magnitude of the discrepancy. This paper emphasizes the need for accurate and reliable assessment of leg length differences using a clinically functional radiographic technique, and reviews the biomechanical implications of leg length inequality as related to the development of stress fractures, low back pain and osteoarthritis. PMID- 1913024 TI - Muscular activity and energy expenditure: biochemistry and physiology of exercising muscle. A report of The Rank Prize Funds Mini-Symposium 1990. PMID- 1913025 TI - Sports insurance and national governing bodies. AB - A postal survey was conducted of the attitudes and advice of Welsh governing bodies of amateur sports and their Cardiff-based clubs towards personal sports insurance. Information on 36 of the 39 sports surveyed (92%) was sufficient for analysis. Twenty-two of these 36 sports (61%) organized insurance at a national level, one at club level (3%) and 13 (36%) provided no insurance advice. Only 12 sports (33%) insisted on mandatory insurance cover. Many sportsmen and women are left to search for an appropriate insurance cover themselves or remain uninsured. Owing the lack of advice in 36% of cases it was decided to survey Cardiff-based insurance brokers to establish what type of policy they would recommend. Only 41% of the brokers were able to offer a suitable policy. Club policies recommended by the Central Council for Physical Recreation provide individuals with the same sports cover (but at a lower premium) as is available from a personal accident policy. However, cover is somewhat inadequate and may provide a false sense of security. Sports with mandatory sports insurance are not necessarily those with the highest risk of disabling injury. PMID- 1913026 TI - Subtalar dislocation in a handball player. PMID- 1913027 TI - Effect of pre-exercise protein ingestion upon VO2, R and perceived exertion during treadmill running. AB - The study investigated the effect of pre-exercise protein ingestion upon the oxygen consumption (VO2), respiratory exchange ratio (R) and perceived exertion (PE) of athletes during treadmill running at intensities of approximately 60, 80, 90 and 100% of their VO2max. Seventeen female athletes aged between 17 and 22 years participated in the study. Subjects completed six assessment sessions, each being preceded by one of the following dietary regimens: a protein solution ingested 3h before assessment (P3), a protein solution ingested 1 h before assessment (P1) and the ingestion of water 1-3 h before assessment (B). The subjects' VO2, R and PE were measured at all exercise intensities using standardized procedures. The results showed that P1 produced significantly higher values for VO2 (P less than 0.05) at all exercise intensities and was associated with an increased PE (P less than 0.01). The findings could have implications for athletes when considering the composition of their pre-exercise meal, especially if performing in activities which require the participants to exercise close to or at their VO2max. PMID- 1913028 TI - Wetsuits, body density and swimming performance. AB - To determine the influence of body composition upon swimming performance with and without wetsuits, 14 competitive female swimmers (mean (s.d.) age, 19.9 (0.9) years) were measured for body density while wearing both wetsuits and normal swimsuits. Subjects swam 400 and 1500 m trials with and without wetsuits, randomly, over a 12-day period. Six subjects participated in an additional trial while wearing neoprene leg-bands fitted over the wetsuit. Mean (s.d.) subject density without and with wetsuits was 1.048 (.009) and 1.021 (.007) g/ml respectively. Wetsuits reduced (P less than 0.05) swim times for the 400 (-4.96%) and 1500 m swim (-3.23%) compared with swimsuit trials. The neoprene bands increased (P less than 0.05) swim times relative to swimsuit and wetsuit trials. With wetsuits, swim times were inversely (P less than 0.05) related to density for the 400 (r = -0.46) and 1500 m swim (r = -0.54) suggesting that wetsuits increase performance by increasing buoyancy and that lean subjects benefit more from wearing wetsuits than do fatter subjects. PMID- 1913029 TI - A formula for comparison of selected sport ball compressibility. AB - The purpose of this study was to develop a formula to determine and compare the compressibility of selected sport balls. Six balls (basketball, volleyball, soccer ball, baseball, handball, golf ball) were dropped ten times from each of four different heights onto a smooth solid surface overlaid with a white sheet of typing paper, overlaid with a sheet of carbon paper. The diameter of the area of contact of each ball imprinted onto the typing paper was measured in millimetres with calipers. From the data, the distance (d) that each ball compressed for each velocity (v) was calculated. It was found that a linear relationship existed between velocity at impact and the distance for each ball studied. The compressibility coefficient (c) for each ball was calculated and a formula was developed to determine the distance each ball would compress at a given velocity. When velocity is measured in metres per second and the distance a ball compresses is measured in millimetres, the formula to determine d for selected balls, in order of compressibility is: basketball d = 3.07v, volleyball d = 2.90v, soccer ball d = 2.80v, baseball d = 0.77v, handball d = 0.53v, and golf ball d = 0.17v. PMID- 1913030 TI - Effect of exercise intensity on postexercise energy expenditure in women. AB - This study was designed to examine the effect of exercise intensity on the magnitude and duration of excess postexercise oxygen consumption (EPOC) in women. On separate days and in a counterbalanced order, seven moderately active young adult women performed a 850 kJ cycle ergometer exercise at an intensity of 40 or 60% of their previously determined peak oxygen uptake (VO2). Baseline VO2 and heart rate (HR) were recorded during the last 10 min of a 45 min seated rest. VO2 and HR were measured continuously during recovery until VO2 returned to baseline. There was no significant difference noted in the baseline measures between the two exercise programmes. Magnitude of EPOC was comparable (P greater than 0.05) being mean (s.d.) of 30(17) and 36(13) kJ after 40 and 60% exercises respectively. Although the EPOC duration was 53% longer following the 40% exercise than following 60% (27(15) min and 18(8) min, respectively) this difference was not statistically significant. These exercise conditions failed to produce a prolonged EPOC in the women of this study, and values recorded for magnitude of EPOC indicate that it was not significant with regard to the overall energy expenditure of the activity. It was concluded that both magnitude and duration of EPOC seemed to be independent of the chosen exercise intensities used by the women in this study. PMID- 1913031 TI - Carbohydrate loading in practice: high muscle glycogen concentration is not certain. AB - It is believed that muscle glycogen resynthesis can be stimulated by depleting the glycogen stores by heavy physical exercise and then eating a diet rich in carbohydrates. In this study, we compared muscle glycogen concentrations after two different depletion and loading procedures in six male runners. The depletion runs for the procedures were a half-marathon race and an easier fartlek. The mean muscle glycogen concentrations (+/- s.e.m.), analysed after the procedures, did not differ significantly between the race and the fartlek being 285 (+/- 25) mmol/kg d.w. (dry weight) versus 315 (+/- 32) mmol/kg d.w. (P greater than 0.05). Moreover, the subjects' glycogen concentrations were not clearly increased above the predepletion values following either procedure. The results show that higher glycogen levels do not necessarily occur after classical carbohydrate-loading procedures. PMID- 1913032 TI - Temporomandibular dysfunction syndrome associated with scuba diving mouthpieces. AB - As previous reports have highlighted that temporomandibular joint dysfunction syndrome can occur during scuba diving due to the use of a diving mouthpiece, 74 divers of varied experience (62 male, 12 female) were asked to evaluate the efficiency of the mouthpiece for the ease of grip, insertion into the mouth, clearing of water, air sharing, comfort and overall efficiency. They also recorded the level of muscle and joint discomfort experienced during diving and non-diving activities. The results indicate that temporomandibular joint problems unrelated to diving are compounded by the use of a diving mouthpiece. The diver's assessment of muscle tension and comfort while using the mouthpiece was found to be a good predictor of whether temporomandibular dysfunction would occur and the assessment scores have been used in a formula to aid selection of a mouthpiece. PMID- 1913033 TI - Avulsion fractures of the proximal tibial epiphysis. AB - Fractures of the tibia through the proximal epiphysis are rare. This injury usually results from severe direct or indirect force about the knee, and has not been described as resulting from a patellar tendon avulsion injury. Four patients presented with five avulsion fractures of the proximal tibial epiphysis. All were older adolescent males who had been engaged in jumping sports when the injury occurred; one had bilateral injury. All the patients were treated by closed reduction and plaster cast immobilization for 4-8 weeks, with satisfactory results. On the basis of our cases and five cases previously reported, the authors would agree with Ryu and Debenham's suggestion that the Watson-Jones classification, which divides avulsion fractures of the tibial tubercle into three types, should be expanded to include this fourth type - avulsion fracture of the proximal tibial epiphysis. PMID- 1913034 TI - Catastrophic rugby injuries of the spinal cord: changing patterns of injury. AB - In reports from the UK and New Zealand, it is noted that the incidence of rugby injuries to the cervical spinal cord has dropped and that the percentage of players injured in the tackle has similarly decreased. In contrast, this does not appear to be the pattern in South Africa and an analysis has therefore been made of 40 rugby players sustaining injuries to the spinal cord during the period 1985 to 1989. The radiological appearances on admission have been correlated with the circumstances of injury, associated orthopaedic injuries and neurological deficits. The tackle was responsible for the majority of injuries, causing more than the scrum. Tackles were also responsible for more cases of complete, permanent quadriplegia than the scrum. The commonest cause of injury in players being tackled was the high tackle around the neck, while the commonest cause of injury in players making the tackle was the dive tackle. This survey has shown that the tackle is now the major cause of spinal cord injury in South African rugby, in contrast to earlier analyses in which the scrum was identified as the most common cause. PMID- 1913035 TI - Sports injuries in children and adolescents. PMID- 1913037 TI - Comparison of colour Doppler ultrasound with venography in the diagnosis of axillary and subclavian vein thrombosis. AB - The primary imaging technique in suspected venous occlusive disease has for many years been contrast venography. Recent studies have shown ultrasound with the addition of colour Doppler imaging to be a suitable alternative method in the diagnosis of lower limb venous thrombosis. We have applied these techniques to the upper limb venous system, and have performed a prospective study of 19 patients (30 limbs) comparing colour Doppler ultrasound with venography in the diagnosis of axillary and subclavian vein thrombosis, for which colour Doppler ultrasound has a sensitivity and specificity of 100%. If vein stenosis is included, the sensitivity falls to 89%. We propose that colour Doppler ultrasound is a suitable first-line alternative to venography in the diagnosis of axillary and subclavian vein thrombosis. In addition to showing the major venous drainage of the upper limb, ultrasound routinely assesses patency of the internal jugular vein, which is, on occasion, of clinical relevance when determining possible future sites of venous access. If, however, colour Doppler ultrasound is normal then bilateral upper limb venography is indicated to exclude a more central venous problem or localized stenotic lesion. PMID- 1913036 TI - Pilot study of the epidemiology of sports injuries and exercise-related morbidity. AB - In the pilot phase of a national study of the incidence of exercise-related morbidity (ERM), funded by the Sports Council, a questionnaire about recent participation in 'active sports and other recreational activities involving vigorous physical exercise' and associated injuries or illnesses was sent to a sample of 6744 people aged 16 to 65 years in two areas. Interviews with 101 respondents were held to validate the questions. Return rates of 73 and 81% from the two areas were achieved and results from the interviews indicated that sports and injuries were being reported sufficiently accurately on the postal questionnaires to yield reliable information. Of the 4961 usable returns, a total of 1249 respondents (25%) reported taking part in some activity in the 4 weeks before completing the questionnaire, and 137 (3%) reported 158 injury incidents. Nearly half (76, 48%) of these incidents resulted in some restriction in activity, and 21 resulted in some restriction in activity, and 21 resulted in a visit to a hospital casualty department. It is estimated that nationally 1-1.5 million episodes of ERM result annually in attendance at a hospital casualty department, and 4-5 million episodes of ERM result in some, usually temporary, incapacity. PMID- 1913038 TI - The effects of sodium nitroprusside on Doppler signals from a soft tissue tumour. AB - In a previous study, we described the effects of systemic vasoconstriction on the Doppler signals from a soft tissue tumour (Taylor et al, 1989). Our conclusions were that vasoconstriction produced significant changes in the signals from normal vessels and enhanced the differences between normal and neoplastic vessel signals. The aim of this study was to determine whether converse changes were produced by vasodilatation. PMID- 1913039 TI - Duplex ultrasound of the common femoral vein in pregnancy and puerperium. AB - The common femoral veins of 34 apparently normal women were examined by ultrasound during or just after pregnancy. The cross sectional areas of these veins were measured at rest in the supine position and during a Valsalva manoeuvre. The veins were also assessed by pulsed Doppler ultrasound. We believe that Doppler examination is superior to calibre response assessment during the Valsalva manoeuvre in excluding an isolated iliac occlusion in women in late pregnancy and in early puerperium. PMID- 1913040 TI - The use of real-time ultrasound in the management of scrotal trauma. AB - 27 patients were studied with real-time ultrasound following severe scrotal trauma. 22 (81.5%) had ultrasound features of scrotal trauma and, of these, five (18.5%) had signs of testicular rupture. Four of these five patients underwent surgery following ultrasound. This confirmed the diagnosis of rupture and the tests were repaired. Ultrasound should be offered to all patients presenting with scrotal trauma to select patients with testicular rupture for surgery. PMID- 1913041 TI - Air aspiration after double-contrast knee arthrography: a worthwhile exercise? AB - A prospective study following double-contrast knee arthrography was undertaken to compare pain and discomfort experienced at the conclusion of the procedure and for 7 days afterwards. The patients were divided into two groups. Half had the air aspirated at the end of the examination and the other half did not. Twice as many patients in the aspirated group were totally asymptomatic (48% compared with 22%); however, by 7 days after the procedure the numbers of asymptomatic patients were similar in the two groups (64% and 63%, respectively). Thus our conclusion is that air aspiration after double-contrast knee arthrography does reduce short term morbidity. PMID- 1913042 TI - Fascioliasis: findings in 15 patients. AB - The clinical and radiological features of 15 cases of fascioliasis are reported. Pleural effusion, associated with pulmonary infiltrates or ascites, was observed in two patients. Computed tomography (CT) was the most useful imaging method, showing small nodules and linear tracks within the liver parenchyma which were hypodense on non-enhanced scans, remaining hypodense or becoming isodense with normal liver after contrast medium administration. After successful treatment lesions decreased in number and size and finally disappeared or calcified. Lesions increased or remained unchanged when treatment failed to control the disease. PMID- 1913044 TI - Dosimetric accuracy at low monitor unit settings. AB - Dosimetric accuracies at low monitor units are evaluated for linear accelerators from various manufacturers. A large error is observed in the majority of the accelerators. The error can be positive or negative. Although the error can exceed 20% for the first few monitor units, it is usually less than 5% when more than 10 monitor units are delivered. When low doses are required proper precautions should be taken for dosimetric accuracy including the beam energy, beam flatness and dose per monitor unit. PMID- 1913043 TI - Prenatal diagnosis of nuchal cystic hygroma. AB - Twenty-seven cases of nuchal cystic hygroma were diagnosed prenatally over a 5 year period at the Birmingham Maternity Hospital. Karyotypes were obtained in 20 cases, of which 14 (70%) were abnormal. Two-thirds of these represented various trisomy syndromes in contrast to other series where cases of Turner's syndrome have predominated. Twenty pregnancies were terminated. There was one intra uterine death and two neonatal deaths. Hydrops was present in 15 cases, none of which survived to term. Associated structural abnormalities, mainly skeletal, renal and cardiac, were present in 18 cases. There were four long-term survivors with good quality of life, including both normal and abnormal karyotypes. In utero regression of the hygroma was documented in five cases, total in three and subtotal in two cases born with residual neck webbing. PMID- 1913045 TI - Tumour size as a prognostic factor in carcinoma of the cervix: assessment by transrectal ultrasound. AB - Transrectal ultrasound (TRUS) was used to measure tumour size in patients with carcinoma of the cervix and to assess its prognostic significance. Clinical staging was conducted and at the time of examination under anaesthesia, TRUS was used to assess maximum transverse diameter of the tumour. Eighty-one patients were studied. FIGO stages were 1B 34 patients, IIA seven patients, IIB 31 patients, IIIA two patients and IIIB seven patients. Mean tumour diameters by stage were IB 37 mm, IIA 37 mm, IIB 49 mm, IIIA 42 mm and IIIB 50 mm. There was a significant correlation between size and stage (p = 0.001). With a median follow up of 18 months, 16 relapses have occurred. The actuarial relapse rates at median follow-up by stage were IB 10%, IIA 17%, IIB 22%, IIIA 0% and IIIB 35%. The actuarial relapse rates by size grouping at median follow-up were less than 30 mm 0%, greater than 30 and less than 40 mm 11%, greater than 40 and less than 50 mm 22%, and greater than 50 mm 38%. There was a significant difference between the mean recorded size of the tumours in the relapsed group and the relapse-free group (p = 0.02). Despite the small number of patients and short follow-up, tumour size as measured by TRUS appears to predict relapse. PMID- 1913046 TI - The relative biological effectiveness of fractionated doses of fast neutrons (42 MeVd----Be) for normal tissues in the pig. IV. Effects on renal function. AB - The effects of fractionated doses of fast neutrons (42 MeVd----Be) on the radiation response of the pig kidney have been assessed and compared with those observed after X irradiation. Following X irradiation there was a marked increase in the total dose at which renal function was preserved with decreasing fraction size. The rate of this increase was dependent on the overall treatment time; for fractionated irradiation given over 18 or 39 days the exponents related to fraction number, N, were 0.36 +/- 0.03 and 0.48 +/- 0.003, respectively. In contrast, there was no significant change in the iso-effect dose for renal injury following fractionated irradiation with fast neutrons where there was also little effect of varying the overall treatment time. Analysing these data by means of the linear-quadratic (LQ) model, using both an Fe-plot and the Tucker test, gave alpha/beta ratios of 2.42 +/- 0.06 Gy and 2.99 +/- 0.16 Gy, respectively, for X ray doses given in 18 days. For fractionated doses of X rays given in 39 days the alpha/beta ratios were 0.40 +/- 0.01 Gy and 0.47 +/- 0.02 Gy, respectively. The alpha/beta ratios for renal tissue following fast neutron irradiation obtained by the two methods were also similar, i.e. 15.00 +/- 0.60 Gy and 15.72 +/- 3.76 Gy, respectively. The pronounced fractionation effect seen with X irradiation, particularly for doses administered over 39 days as opposed to 18 days, coupled with the absence of any such effect with fast neutrons, resulted in a marked increase in relative biological effectiveness (RBE) with decreasing X-ray dose/fraction. The slopes of the resulting regression lines were -0.73 +/- 0.05 and -0.33 +/- 0.02, respectively. The lack of dose sparing associated with fractionation, or variation of the overall treatment time for fast neutron irradiation, suggests that doses administered to tumours adjacent to the kidney can be given as a few relatively large dose/fractions in a short overall treatment time without an increased risk of complications related to renal tissue. This may be of therapeutic advantage in the treatment of rapidly proliferating tumours where dose may be wasted using more conventional protracted fractionated irradiation schedules. PMID- 1913048 TI - Memorandum from the Institute of Physical Sciences in Medicine. Back-scatter and F-factors for low- and medium-energy X-ray beams in radiotherapy. Working Party of the Institute of Physical Sciences in Medicine. PMID- 1913047 TI - Design of a database with graphical analysis for X-ray quality assurance and dose information to assist in a programme for patient dose reduction. AB - A database system has been set up on an IBM PC to store X-ray quality assurance (QA) data and patient doses for all X-ray equipment operated by Grampian Health Board. Graphical analysis facilities have been developed to display data in a readily understandable form. Data on equipment specifications, QA test results, exposure factors for standard examinations, and thermoluminescent dosemeter (TLD) measurements of patient skin doses are stored in separate forms. X-ray machine outputs are fitted to a simple polynomial equation, and the data combined with information on exposure factors to calculate entrance doses for selected examinations. Data such as filtration and backscatter factors are derived from look-up tables for use in dose calculations. Histogram comparisons can be made between calculated doses, means of TLD measurements and National Radiological Protection Board reference levels to allow units giving high skin doses to be identified so that corrective actin can be taken. PMID- 1913049 TI - Measuring the filtration of mammographic X-ray tubes with molybdenum targets. PMID- 1913050 TI - Malignant melanoma of the vulva: response to radiation. PMID- 1913051 TI - Melnick-Needles syndrome (osteodysplasty) in an older male--report of a case and a review of the literature. PMID- 1913052 TI - What is it? Intraosseous lipoma in a 13-year-old boy. PMID- 1913053 TI - Post-mastectomy lymphangiosarcoma (Stewart-Treves syndrome): report of two long term survivals. PMID- 1913054 TI - Acute epidural haematoma complicating myelography in a normotensive patient with normal blood coagulability. PMID- 1913055 TI - Spinal cord compression in Paget's disease due to extradural pagetic ossification. PMID- 1913056 TI - A pain in the neck! PMID- 1913057 TI - The use of a disposable nasoduodenal feeding tube for the small bowel enema examination. PMID- 1913058 TI - Radiosensitization by 17 atmospheres pressure of air. PMID- 1913059 TI - Dysphagia after fast neutron therapy to the head and neck. PMID- 1913060 TI - The application of information technology in urology. PMID- 1913061 TI - Experience with sperm counts following vasectomy. AB - The records of Aberdeen men requesting vasectomy between 1978 and 1981 were studied and a sample of men were interviewed about 3 years after the operation; 85% completed the standard requirements for seminal analysis and were given the "all clear"; two-thirds were cleared after sending 2 samples and usually within 20 weeks after vasectomy; 10% of men sent at least 1 sample but were never cleared and the remaining 5% ignored the requirements. Information from 70 men (63 interviews, 7 questionnaires) gave some indication of reasons, often multiple, for incomplete or non-compliance; these included embarrassment, ambiguous feelings about having more children, inadequate understanding of reproductive physiology and blind faith in the surgeon. PMID- 1913062 TI - Cystine stones: the impact of new treatment. AB - The hardness and frequent recurrence of cystine stones present a special challenge to the urologist. In this study, 15 cystinuric patients (11 males, 4 females; mean age 36 years, range 17-54) were treated and followed up over a period of 30 months (range 2-40). Most patients had previous history of open surgery. The diagnosis of cystinuria was confirmed by metabolic studies and infrared spectrometry of stones. Over the follow-up period recurrence was observed in 23 instances in 11 patients, leading to 38 "stone treatments" on 74 cystine stones. The percutaneous approach was used alone in 9 cases and in association with extracorporeal shock wave lithotripsy (ESWL) in 9 cases. ESWL was used alone in 18 cases. Medical treatment included high fluid intake, alkalinisation and Thiola (tiopronin, N-(2-mercaptopropionyl)glycine) in 6 patients. The overall stone-free rate assessed 3 months after treatment was 44.7%, which compares poorly with the rate for non-cystine stones. The recurrence rate is very high and instrumental treatment should not therefore be used excessively; it is indicated only for stones that are symptomatic or refractory to intensive medical therapy. PMID- 1913063 TI - The effect of diclofenac sodium on urinary concentration of calcium, uric acid and glycosaminoglycans in traumatic paraplegics. AB - Non-steroidal anti-inflammatory drugs (NSAID) have been shown to decrease calcium excretion in the experimental animal, in human volunteers and in calcium stone formers. Paraplegics tend to be hypercalciuric during the first 2 years after their injury and this is said to be a predisposing factor for stone formation in these patients. The effect of the NSAID diclofenac sodium was studied in 12 traumatic paraplegics who had sustained their injury 1 to 6 months previously; 24 h urine samples collected before and 2 weeks and 4 weeks after oral diclofenac sodium 50 mg tds were analysed for calcium, uric acid, glycosaminoglycans (GAGs) and volume. There were no significant changes in urinary volume, uric acid and GAGs excretion. However, urinary calcium concentration and 24-h calcium excretion decreased significantly following 2 weeks' and 4 weeks' treatment with diclofenac sodium. PMID- 1913064 TI - Cystometric, physiological and morphological studies after relief of bladder outflow obstruction in the pig. AB - Experimental bladder outflow obstruction was relieved in 18 pigs between 2 and 15 months after the creation of partial urethral obstruction. Cystometric, physiological and morphological studies were performed 2 to 6 months after relief of the obstruction. An increase in average voiding flow rates from 2.8 +/- 1.0 ml/s to 6.8 +/- 1.2 ml/s was recorded in the Landrace pigs and from 2.2 +/- 0.9 ml/s to 7.4 +/- 1.4 ml/s in the Gottingen mini-pigs. There was a concomitant decrease in the voiding detrusor pressures from 52 +/- 11 cm H2O to 32 +/- 8 cm H2O and from 78 +/- 12 cm H2O to 33 +/- 6 cm H2O respectively. A return towards control values of the physiological responses to exogenously applied agonists (acetylcholine and potassium) and to electrical field stimulation was observed. There was an increase in neuronal innervation in the morphological studies which was more marked in the animals with a shorter period of obstruction. The implications for patient care are discussed. PMID- 1913065 TI - Adenocarcinoma of the bladder: study of 14 cases and review of the literature. AB - Fourteen patients with adenocarcinoma of the bladder have been seen over a 14 year period; 6 tumours were of urachal origin and the remaining 8 were primary. All tumours were muscle-infiltrating. The 6 patients with urachal tumours were subjected to surgery; 3 underwent partial cystectomy and 3 radical total cystectomy. All patients who underwent partial cystectomy are alive and free of disease at 60 months, 12 months and 12 months respectively. The other 3 patients who underwent radical cystectomy suffered recurrence and 2 succumbed to their disease within 1 year. All patients with primary adenocarcinoma of the bladder underwent radical cystectomy, 5 of them after planned pre-operative radiotherapy. There were 3 post-operative deaths. One patient died of an unrelated cause 30 months after surgery and 2 died of disseminated disease 8 and 16 months after surgery. One patient developed inguinal lymph node metastases 4 months after surgery and is controlled at 12 months with radiotherapy. Only 1 of the 8 patients with primary adenocarcinoma of the bladder is alive and free of disease at 6 months. PMID- 1913066 TI - Neuro-endocrine cells--a new prognostic parameter in prostate cancer. AB - Neuro-endocrine cells are a recognised component of prostatic ducts and acini. Half of all clinically manifest cancers show neuro-endocrine differentiation. Occult carcinomas have a lower incidence of such differentiation. Neuro-endocrine cells are of major prognostic importance and appear more reliable in predicting patients' survival than do conventional histological grading systems. PMID- 1913067 TI - Urethral pressures: analysis of transmission pressure ratios. AB - Transmission pressure ratio (TPR) analysis of urethral pressure profilometry data has been advocated for the diagnosis of genuine stress incontinence (GSI). However, the clinical usefulness of the technique has not been adequately evaluated. Using videourodynamics as the gold standard, the TPR results of 150 continent women and 153 with GSI have been compared. The mean TPR for each quartile of the functional urethral length was computed, as was the maximum TPR value (TPR-max) and the position on the urethra where it occurred (TPR-mode). There was a statistically significant difference between the 2 groups for TPR values in the distal 2 quartiles of the urethra and for TPR-max and TPR-mode. With the use of the Kappa statistic it was found that the TPR-mode was the most discriminatory of the TPR parameters. Even using this measure, the overlap between normal and GSI was so great as to make accurate diagnosis impossible. It was therefore concluded that TPR analysis is useless for the diagnosis of GSI. However, such an analysis is helpful for the understanding of the pathophysiology of GSI and its treatment. PMID- 1913068 TI - Presentation and management of urethral calculi. AB - A total of 36 patients with urethral calculi are presented; 34 were males, aged 2 to 65 years (mean 43). Eight patients were under the age of 6 years and presented with retention of urine. Calculi were in the posterior urethra in 56% of the patients, 33% had associated urinary tract calculi, and 47% had other diseases of the lower urinary tract, the commonest being posterior urethral stricture (42%). Of these calculi, 58% could be manipulated endoscopically into the urinary bladder, then crushed. Associated urethral strictures were dealt with by visual internal urethrotomy before manipulating the calculi. Other methods of treatment and their complications are discussed. PMID- 1913069 TI - The role of delayed primary repair in the acute management of pelvic fracture injuries of the urethra. AB - The principal aim of management of the ruptured urethra should be to do everything possible to reduce the long-term complication rate and this applies principally to stricture formation. By far the most difficult complication to treat is severe distraction; thus the aim of early management should be to recognise and correct severe distraction injuries. Delayed primary repair at 7 to 10 days is recommended for this problem. The aim is not to prevent a stricture occurring but to make sure that if it does occur it is easily treatable. PMID- 1913070 TI - Cysts of the tunica albuginea--more common testicular masses than previously thought? AB - Cysts of the tunica albuginea have been considered very rare. Their clinical significance lies in their presentation as discrete testicular masses often diagnosed as malignancies prior to removal. We report our experience with 6 cases of cysts of the tunica albuginea over a 12-year period and review the relevant literature. It is obvious that these cysts can be both of epithelial and of mesothelial origin. Our material includes a cyst lined by a transitional-like epithelium, of a kind to our knowledge not reported previously. All of the cysts were found by palpation and they constituted 6% of the testicular tumours examined over the same period. High-resolution ultrasound examination can distinguish them from solid testicular masses, as in 2 cases here, thus enabling unnecessary operations to be avoided. PMID- 1913071 TI - Surgery following chemotherapy for metastatic testicular teratoma. AB - Twenty patients with metastatic testicular teratoma underwent surgery for residual disease after chemotherapy. Twelve patients in whom complete excision of all residual masses was possible are alive with no evidence of disease. Four patients have died of malignant teratoma, 2 have active malignant disease and 2 have inoperable residual cystic disease. Patients with malignant teratoma intermediate (MTI) primary testis tumours, and those with bulky abdominal disease at presentation, are more likely to have residual masses requiring excision. Completeness of excision appears to be the most important predictor of disease free survival. PMID- 1913072 TI - Imaging properties of polydioxanone and titanium ligating clips following para aortic lymphadenectomy for testicular cancer. AB - Stainless steel ligating clips produce serious artefacts on CT scans. Polydioxanone (PDS) and titanium ligating clips were used in 15 patients during para-aortic lymphadenectomy for residual metastatic testicular teratoma following chemotherapy, and follow-up CT images were compared with those following the use of stainless steel ligating clips. PDS ligating clips did not produce any artefacts and were progressively absorbed. Titanium ligating clips produced artefacts similar to but less intense than those of stainless steel. PDS ligating clips should be used when follow-up CT scanning is important. PMID- 1913073 TI - Antenatally detected pelviureteric junction obstruction. Is non-operation safe? AB - We report follow-up data (minimum of 1 year) on 63 kidneys with antenatally detected pelviureteric junction obstruction, as defined by renographic criteria. The condition was bilateral in 10 patients (i.e. 20 kidneys), 2 patients had unilateral obstruction with contralateral multicystic dysplastic kidneys, and 41 patients had unilateral obstruction with a normal contralateral kidney. In the latter group, 29 (71%) had good function (greater than 40%) at initial assessment. Of the 63 kidneys, 24 (38%) were operated upon following initial assessment, mainly for impaired function. Of 39 patients, initially managed non operatively, 8 (21%) were operated upon subsequently: 3 for deteriorating function (2 of whom have been reassessed and both have regained their lost function) and 5 for other renographic or ultrasonic indications). Of the original 63 kidneys, 31 (49%) continue to be managed non-operatively; 16 of these (52%) show improving ultrasound appearances, 8 of 17 studied show improved drainage, and all unilateral cases have stable good function. It is concluded that non operative management of selected cases of antenatally detected pelviureteric junction obstruction is safe. PMID- 1913075 TI - Application of the onlay island flap urethroplasty to penile hypospadias with severe chordee. AB - The onlay island flap urethroplasty was originally used to repair anterior hypospadias without chordee and was later used to repair penile hypospadias with a well developed urethral plate exhibiting little or no chordee after release of skin tethering. It is possible to treat all cases of penile hypospadias even with severe chordee by releasing the chordee without dividing the urethral plate and by reconstructing the urethra with an onlay island flap. PMID- 1913074 TI - Blood and urine analysis in patients with intestinal bladders. AB - A group of 183 patients whose urine was stored in pouches formed either wholly or partly from bowel was reviewed to establish abnormal biochemical and haematological factors and to assess the risk of infection. Minimum follow-up was 1 year (range 1-28.5, mean 3 years 8 months) and the mean age of the patients at follow-up was 16.5 years (range 4-43). Pouches were augmentation and substitution cystoplasties and complete reconstructions with bowel. Bowel segments were ileum (55 patients), colon (100) and mixed (28). Anaemia was found in 15 patients, folate deficiency in 2 and folate excess in 2. Definite hyperchloraemic acidosis was found in 25 patients and borderline results in 40. Most of these patients had colon in the pouch but 5 definite and 13 borderline cases had ileum only. Troublesome urinary infections occurred in 27.9% of patients; 3 developed renal stones and 22 developed pouch/bladder stones. Stones were usually associated with infection and/or staples. Delayed linear growth occurred in 20% of children in spite of a normal increase in weight; there was no difference in any of the measurements between those who grew and those who did not. PMID- 1913076 TI - Carcinoma of the prostate presenting as impotence. PMID- 1913077 TI - Verrucous carcinoma of vesical diverticulum. PMID- 1913078 TI - Renogastric fistula. PMID- 1913079 TI - Diagnosis and management of large seminal vesicle stones. PMID- 1913080 TI - Primary malignant lymphoma of the bladder. PMID- 1913081 TI - Late perinephric abscess formation after extracorporeal shock wave lithotripsy. PMID- 1913082 TI - Spontaneous renocolic fistula in vesicoureteric reflux. PMID- 1913083 TI - Unusual migration of a ureteric calculus. PMID- 1913084 TI - Coronal haemostatic suture for partial nephrectomy. PMID- 1913085 TI - Badenoch's pull-through procedure in the management of urethrorectal fistulae. PMID- 1913086 TI - An appliance to direct urine flow following penile amputation. PMID- 1913087 TI - Re: Skin bridge--a complication of paediatric circumcision. PMID- 1913088 TI - Re: A pitfall in the diagnosis of supernumerary kidney. PMID- 1913089 TI - Re: Foley catheter balloon puncture and the risk of free fragment formation. PMID- 1913090 TI - Re: Ureteric substitution with Boari bladder flap. PMID- 1913091 TI - Comparison of iliofemoral and femorofemoral crossover bypass in the treatment of unilateral iliac arterial occlusive disease. AB - Between 1981 and 1988, 74 synthetic crossover bypass grafts were inserted for unilateral iliac arterial occlusive disease. In 32 patients the bypass procedure was iliofemoral and in 42 femorofemoral. The cumulative patency rate at a mean of 2.7 years was 79 per cent in both groups. There was no significant difference in either postoperative mortality rate or duration of hospital stay. Iliofemoral bypass may offer significant advantages over the femorofemoral approach. In particular it avoids a groin incision in the donor limb, leaving the common femoral artery intact for subsequent angioplasty or reconstruction should proximal stenotic disease develop in the donor iliac vessel. PMID- 1913092 TI - Value of duplex scanning compared with angiography and pressure measurement in the assessment of aortoiliac arterial lesions. AB - To detect haemodynamically significant lesions in the aortoiliac arteries, invasive tests such as angiography and intra-arterial pressure measurement (IAPM) are considered valuable diagnostic tools. The value of duplex scanning as a direct non-invasive examination technique was prospectively compared with intra arterial digital subtraction angiography (IADSA) and IAPM at rest, and after the administration of papaverine in 60 patients. Excellent agreement, as assessed by the kappa statistic, was shown between duplex scanning and IADSA (kappa = 0.81). A fair agreement was shown between duplex scanning and IAPM (kappa = 0.63), and between IADSA and IAPM (kappa = 0.63). Duplex scanning and IADSA both missed some less haemodynamically critical lesions if IAPM was considered the 'gold standard'. It is concluded that duplex scanning detects haemodynamically significant lesions as effectively as angiography and so may be considered a new and valuable diagnostic tool. IAPM remains necessary to detect some lesions of borderline haemodynamic significance. However, with future developments, duplex scanning has the potential to replace the need even for IAPM. PMID- 1913093 TI - Fibrinolytic activity and calf pump failure. AB - The interstitial fibrinolytic activity of the upper and lower limbs was investigated in subjects with abnormal calf pump function by measuring the lysis rate of experimentally produced subcutaneous 125I-fibrin clots. Thirty-three subjects with healed venous ulcers, five with varicose veins and 11 controls were studied. 125I-fibrin clots were produced in the subcutaneous tissue of the forearms and legs and clearance half-life was calculated. Calf pump function was assessed by foot volumetry and the 'gaiter' skin nutritive circulation by measuring the transcutaneous oxygen tension (PtcO2). Fibrin clearance was prolonged from the subcutaneous tissues of the legs of subjects with varicose veins and healed ulcers compared with controls. Negative correlations were found between fibrin clearance half-life and the half-volume refilling time (P less than 0.01) and the PtcO2 (P less than 0.01). PMID- 1913095 TI - A new instrument: the toothed cutting forceps. PMID- 1913094 TI - Cervical spine injuries in patients with head injuries. AB - It is generally believed that significant head injury after a traffic accident or fall is associated with a high incidence of concurrent cervical spine injury. This study prospectively examined 260 victims of traffic accidents or falls with significant head injury. The incidence of associated cervical spinal injury was only 3.5 per cent. There was no association between the severity of head injury and the incidence of cervical spine injury. The risk of concurrent spinal injury in head injury patients is not higher than the reported risk in patients without head injury. Although care should be taken to protect the cervical spine in patients with head injury, the results of the present investigation show that the risk of cervical spine injury is much less than previously reported. PMID- 1913096 TI - Pylorus-preserving 'cluster' operation. PMID- 1913097 TI - New prosthetic venous collar anastomotic technique: combining the best of other procedures. PMID- 1913098 TI - The British Journal of Surgery--facts and figures. PMID- 1913099 TI - Surgical management of primary hyperhidrosis. PMID- 1913100 TI - Experimental study of starch-induced intraperitoneal adhesions. PMID- 1913101 TI - Justifying arterial reconstruction to crural vessels--even with a prosthetic graft. PMID- 1913102 TI - Management of idiopathic megarectum and megacolon. PMID- 1913103 TI - Gynaecomastia. AB - This paper reviews the development of excess breast tissue in the male. Gynaecomastia is a common problem and may have a physiological or pathological basis. It can be dealt with in most cases by reassurance or simple surgery. PMID- 1913104 TI - Limitations of surgery in the treatment of retroperitoneal sarcoma. AB - A retrospective analysis was undertaken of 120 patients with retroperitoneal sarcoma referred to the Royal Marsden Hospital over a period of 20 years. The actuarial 5-year survival rate of all cases following referral was 29 per cent. On univariate and multivariate analysis the principal factors associated with an unfavourable prognosis were the presence of metastases, poor performance status at presentation, high tumour grade and incomplete excision of the primary tumour. The single most important factor affecting the ability to remove the primary tumour completely was multiple organ involvement. After apparently complete excision, however, the probability of local recurrence by 5 years was 85 per cent (95 per cent confidence interval 56-99). The prognosis of patients with retroperitoneal sarcoma is poor. PMID- 1913105 TI - Clinical and functional results of abdominal rectopexy for complete rectal prolapse. AB - Between 1977 and 1987, 53 patients underwent polyvinyl alcohol sponge rectopexy for complete rectal prolapse. The mean follow-up period was 36.7 months. Full thickness prolapse recurred in two patients (3.8 per cent). Infection around the prosthesis and faecal impaction developed in two patients each. Continence improved significantly after operation, particularly in those under 70 years of age (P = 0.028, chi 2 test) and nulliparous women (P = 0.026, chi 2 test). Bowel function was generally unchanged after rectopexy; in particular only eight patients (15 per cent) had significant postoperative constipation. PMID- 1913106 TI - Healing of abdominal incisional hernia in infant rats. AB - Incisional hernia following major laparotomy in adult humans occurs in 5 per cent of cases. Spontaneous healing of such hernias does not occur. We have devised a model for producing abdominal wall incisional hernia in the rat by dividing the linea alba subcutaneously through a small transverse skin incision. In adult rats (n = 17), an incisional hernia formed and progressively increased in size over 32 weeks. In 3-week-old infant rats (n = 17), all developed herniation immediately. In eight rats, these hernias progressively increased. In three, the hernias were healed at the third week, but recurred at the fourth, eighth and 12th weeks, respectively. In the remaining six animals, the hernias healed spontaneously at 3 weeks and remained healed. A similar observation of spontaneous healing of incisional hernias in children has been reported in one clinical paper. This animal model provides a useful means of studying the clinical difference between adult and infant with respect to incisional hernia. PMID- 1913107 TI - Histopathological evaluation of oesophageal carcinoma: the significance of venous invasion. AB - Follow-up data on 115 patients who had undergone surgical resection for oesophageal carcinoma were analysed. Histological sections were reviewed for tumour classification, grading and staging, and special stains were used to detect venous invasion. The effect of various factors on survival was statistically analysed using Cox's proportional hazards regression model. In this multivariate analysis lymph node metastasis was the most important variable in the assessment of survival (improvement chi 2 = 7.43, P = 0.006). Venous invasion, which was demonstrated with a frequency of 76.5 per cent (mostly intramural) was the second most important prognostic factor (improvement chi 2 = 2.86, P = 0.09). The relative risk for the presence of both variables was rather modest (3.09). PMID- 1913108 TI - The sphinctometer: a new device for measurement of lower oesophageal sphincter function. AB - Current evidence suggests that lower oesophageal sphincter (LOS) competence depends upon both pressure and length. Existing devices can measure length and pressure, but not simultaneously. This methodological problem is a fundamental drawback to understanding LOS function and its role in oesophageal disease. A 'sphinctometer' has been developed, consisting of an oil-filled 3-mm diameter Silastic chamber, 6 cm in length, incorporating a pressure microtransducer designed to provide an integrated pressure reading as a function of length. Its performance has been tested in vitro using human cadaver oesophagus in a specially constructed chamber in which sphincter length and pressure can be varied independently. Comparisons were made with a conventional pull-through technique. Sphinctometer response was linear throughout the LOS pressure range of 0 to 50 mmHg at a fixed LOS length (RS = 0.99; P less than 0.001). Sphinctometer response was also linear at fixed LOS pressure for sphincter lengths from 1 to 6 cm (RS = 0.99; P less than 0.001). This device thus appeared suitable for monitoring function of the human LOS, and has subsequently been successfully incorporated into an ambulatory system for patient use. PMID- 1913109 TI - Outcome of stapled revision of retracted ileostomy. PMID- 1913110 TI - Oxygenation in the stomach and the effect of truncal vagotomy. AB - A Clark polarographic oxygen electrode allowed detailed mapping of tissue oxygen (PtO2) levels on the anterior surface of the stomach in five patients undergoing cholecystectomy. No significant difference in mean PtO2 was detectable between greater and lesser curvatures. A significant difference in mean PtO2 was detected between the body of the stomach and the pylorus (Mann-Whitney, P less than 0.01). The effect of truncal vagotomy on PtO2 was evaluated in six patients undergoing this procedure for duodenal ulceration. Mean postvagotomy stomach PtO2 levels (46 +/- 12 mmHg) were significantly lower (Wilcoxon test, P less than 0.001) than prevagotomy levels (59 +/- 14 mmHg). Truncal vagotomy did not have any significant effect on small intestinal PtO2. This work provides the first objective evidence of the relatively diminished tissue oxygenation in the gastric antrum and pyloric region, and confirms blood flow studies of the effects of vagotomy. PMID- 1913111 TI - Recurrent peptic ulceration after highly selective vagotomy: long-term outcome. AB - A prospective assessment was made of the outcome 4 years after diagnosis of recurrence in a group of 27 patients with documented ulceration after highly selective vagotomy (16 symptomatic recurrence and 11 asymptomatic). In the 16 patients with a previous symptomatic recurrence, eight of the 11 patients with duodenal ulcer underwent a further endoscopy at 4 years and one active ulcer was found. Five patients with previous symptomatic gastric ulcer recurrence have all undergone further surgery. In the 11 patients who originally had an asymptomatic ulcer recurrence (five gastric, six duodenal) no patient has undergone further surgery, although two patients with a recurrent gastric ulcer and two with a recurrent duodenal ulcer subsequently developed symptoms from their ulcer and required H2 receptor blocker therapy. Eight of the 11 originally asymptomatic patients underwent further endoscopy at 4 years and two further duodenal ulcers were found. After highly selective vagotomy, asymptomatic ulcer recurrence occurs frequently and 40 per cent of these patients may develop symptoms. PMID- 1913113 TI - Endoscopic balloon tamponade of iatrogenic bleeding from oesophageal varices. PMID- 1913112 TI - The modified AFP score: an attempt to make the results of anti-reflux surgery comparable. AB - Comparison of different strategies in anti-reflux therapy is complicated by wide variations in patient selection and in the criteria employed to assess outcome. A modification of the classification system originally developed by Bancewicz et al. was used to grade a series of 57 patients before and after fundoplication (primary reflux group). An additional group of 39 patients with an unsatisfactory result after previous Nissen fundoplication (failed Nissen group) were assessed before and after reoperation. The classification system used comprises three elements: the A element depicts gastro-oesophageal anatomy based on the findings at endoscopy: the F element codes the amount of acid reflux by means of 24-h intra-oesophageal pH monitoring; and the P element describes mucosal abnormalities. The overall severity was quantified by means of a score on a scale from 0 to 10. The mean preoperative score in the primary reflux group was 5.45 and in the failed Nissen group 7.3. After fundoplication, this was reduced to 1.07 and 1.30, respectively. In general, there was good correlation between the results of the three elements under consideration, pointing to a potential pathophysiological inter-relationship. Marked individual variation did occasionally occur. The AFP system enabled a detailed description of the preoperative and postoperative condition of the patient, and proved easy to use in clinical practice. Its employment is recommended as an objective means of comparing the value of different treatment strategies. PMID- 1913114 TI - Laparoscopic ligamentum teres (round ligament) cardiopexy. AB - A technique of laparoscopic ligamentum teres cardiopexy for reflux oesophagitis unresponsive to medical treatment is described. The procedure has been performed on five patients and on postoperative testing has been shown to achieve competence of the lower oesophageal sphincter by lengthening of the intra abdominal segment, accentuation of the angle of His and elevation of the pressure in the high pressure zone. All the patients have been relieved of their symptoms by the operation and have not sustained any adverse effects but the follow-up period is short. PMID- 1913115 TI - Gastrointestinal mucormycosis. AB - Twenty patients with gastrointestinal mucormycosis are reviewed. This often fatal opportunistic fungal infection was diagnosed histologically, and was categorized as colonization (five patients), infiltration (seven patients), or vascular invasion (eight patients). There were no fatalities from colonization. In 10 patients, mucormycosis complicated peptic ulcer disease. Seven of these patients had infiltrative or invasive disease. The presentation and operative findings mimicked malignancy in five of these seven patients, and six had successful surgical intervention. The other patient was cured by medical therapy alone. Ten patients had infection associated with other gastrointestinal diseases: post traumatic peritonitis (four patients), transmural amoebiasis (two patients), tuberculosis (one patient), gastroenteritis (one patient), gastric carcinoma (one patient) and diabetes (one patient). Eight patients had significant infection and only one survived. In this series, mucormycosis had a less aggressive course when complicating peptic ulcer than when it occurred in association with other gut diseases. PMID- 1913117 TI - Percutaneous flexible choledochoscopy: a simple method for retained common bile duct stone removal. AB - Conventional methods of treatment of retained common bile duct stones found on T tube cholangiography after common bile duct exploration include percutaneous extraction under fluoroscopic control and endoscopic sphincterotomy. Four cases of percutaneous stone extraction under direct vision using the flexible choledochoscope are described. Clearance of the bile ducts was achieved at one sitting in three cases and four sittings in one case. Follow-up tube cholangiography was performed in two cases and confirmed complete clearance. Percutaneous endoscopic stone extraction can be performed by any surgeon with experience of flexible choledochoscopy and offers the advantages of a minimally invasive procedure without the use of specialized equipment. PMID- 1913116 TI - Chemotherapy and surgery for locally advanced cancer of the cardia and fundus: phase II study with methotrexate and 5-fluorouracil. AB - Locally advanced cancer of the cardia and fundus might be cured by surgical resection. Poor results after surgery in stage IIIB and stage IV disease prompted a study of neoadjuvant chemotherapy. Treatment included four cycles of high doses of methotrexate (1.5 g/m2) and high doses of 5-fluorouracil (1.5 g/m2) followed by surgery in those patients with lesions then found to be resectable. Twenty patients with tumours staged as IIIB or IV were entered; 17 patients completed the four courses of chemotherapy and 14 underwent re-exploration. Eight patients achieved tumour reduction enabling resection. Five patients underwent total gastrectomy with distal pancreatectomy and splenectomy en bloc and three patients had an oesophagogastrectomy. There were no treatment-related deaths and toxicity was tolerable. Two patients were alive 54 and 41 months after chemotherapy with no evidence of disease. Locoregional recurrence developed in five patients and metastatic disease in one. Their median survival was 22 months. PMID- 1913119 TI - Non-operative management of blunt liver injuries. AB - Over a 10-year period 281 patients with liver injuries following blunt abdominal trauma were seen at Westmead Hospital. A decision to treat the liver injury without an operation was made in 55 (20 per cent) of the 281 patients. Two of these 55 patients required a subsequent laparotomy, one for continued bleeding and one for a bile leak. No patient died from a missed intra-abdominal or retroperitoneal injury or from concealed haemorrhage. These patients were compared with 181 patients with liver injuries who were operated on. The two groups of patients could be distinguished in terms of their clinical status on arrival at the hospital, the magnitude of their injury and the sequelae of the injury. Non-operative management proved a safe alternative to an operation in appropriate patients, but a laparotomy to exclude unsuspected intra-abdominal injuries is associated with little significant morbidity and offers some reassurance in managing patients with multiple injuries. PMID- 1913118 TI - Influence of cholecystectomy on symptoms. AB - A group of 292 consecutive patients underwent cholecystectomy for gallstones with presumed biliary pain over a 4-year period and all completed a self-assessment questionnaire before operation. Over the following 2 years 18 patients died but no others were lost to follow-up. The remaining 274 patients completed a further questionnaire 1 and 2 years after operation. Demographic characteristics and abdominal symptoms have been compared with an age- and sex-matched control group using the same questionnaire. Before operation symptoms of flatulent dyspepsia were far more frequent in patients with gallstones but operation markedly reduced these symptoms to an incidence which almost matched that of the control group. However, 1 year after cholecystectomy 34 per cent of patients still suffered some abdominal pain and of 35 patients referred back to hospital for investigation none has been shown to have a retained bile duct stone at a minimum follow-up of 5 years. A multivariate analysis indicated that preoperative flatulence together with long duration of attacks of pain are risk factors for postoperative dissatisfaction as judged by a linear analogue scale. However, both these factors are common and neither is a good discriminator of a poor outcome. The prediction of a poor symptomatic outcome after cholecystectomy from preoperative symptoms or patient characteristics had only limited success and all patients should be warned of this risk. PMID- 1913120 TI - Mediastinal transfixion with a crossbow bolt. PMID- 1913121 TI - Distal pancreatectomy with and without splenectomy. AB - Splenectomy is performed routinely during distal pancreatectomy, yet the spleen has an important role in host defence and can often be preserved. A personal series of 100 distal pancreatectomies undertaken for pancreatic disease between 1978 and 1990 included 23 patients undergoing total pancreatic resection. The remaining 77 patients, who form the basis of the present report, underwent primary distal pancreatectomy and comprised 34 women and 43 men with a median age of 41 years (range 17-78 years). Conventional distal pancreatectomy including splenectomy was performed in 42 patients (55 per cent) for chronic pancreatitis (34 patients), pancreatic neoplasia (six patients), suspected pancreatitis (one patient) or pancreatitic trauma (one patient). Conservative resection with splenic preservation was performed in 35 patients (45 per cent) for chronic pancreatitis (12 patients), suspected pancreatitis (13 patients, including eight patients with pancreas divisum), pancreatic neoplasia (six patients), recurrent acute pancreatitis (two patients) and pancreatic trauma (two patients). There were no postoperative deaths in either group. Early complications followed conventional resection in 10 patients (24 per cent) and conservative resection in seven patients (20 per cent). In five patients the splenic vessels were ligated away from the splenic hilum and the spleen was left in situ, but subsequent isotope scans and haematological indices showed no hyposplenism. The spleen can safely be preserved in many distal pancreatic resections, including those for inflammatory disease, and we now prefer a retrograde technique for dissecting the pancreas off the splenic vessels. PMID- 1913122 TI - Pancreatic pseudocysts: a proposed classification and its management implications. AB - Pancreatic pseudocysts in 83 patients were classified according to clinical and radiographic criteria. Group I (45 patients) had acute, 'post-necrotic' pseudocysts with normal pancreatic duct anatomy and rarely duct-pseudocyst communication. Percutaneous drainage was curative in all patients in whom it was used. Group II (26 patients) included 'post-necrotic' pseudocysts developing in patients already suffering from chronic pancreatitis. The pancreatic duct was diseased but not strictured, and duct-pseudocyst communication was often present. Percutaneous drainage is possible for such patients but it may have to be prolonged; surgical internal drainage was usually successful. Group III (12 patients) had chronic 'retention' pseudocysts. The pancreatic duct was grossly diseased and strictured and duct-pseudocyst communication was present in all cases. Percutaneous drainage is contraindicated and surgical internal drainage has a high recurrence rate. Operative procedures in this group should address the specific ductal pathology. An improved classification of pseudocysts could help the surgeon to choose the most appropriate form of treatment. PMID- 1913123 TI - Randomized trial of intra-arterial recombinant tissue plasminogen activator, intravenous recombinant tissue plasminogen activator and intra-arterial streptokinase in peripheral arterial thrombolysis. AB - Sixty patients were recruited into a randomized parallel group comparison of three thrombolytic regimens for acute or subacute peripheral arterial thrombosis. There were no significant differences in age, duration of history, length of occlusion or presence of neurosensory deficit between the groups. Initially successful lysis was significantly greater with intra-arterial (IA) recombinant tissue plasminogen activator (rt-PA) than with either streptokinase (Sk) (P less than 0.04) or intravenous (IV) rt-PA (P less than 0.01). The duration of therapy varied from a median of 35 h with IA rt-PA to 40 h with Sk (P greater than 0.5). The median (confidence interval) increase in ankle:brachial pressure index following IA rt-PA of 0.57 (0.33-0.82) was significantly higher than for either Sk of 0.24 (0-0.57) or for IV rt-PA of 0.18 (0-0.41). Limb salvage at 30 days was achieved in 80, 60 and 45 per cent respectively for IA rt-PA, Sk and IV rt-PA. Haemorrhagic complications occurred in six patients following Sk and in 13 following IV rt-PA; only one minor haemorrhage occurred following a catheter perforation in a patient who received IA rt-PA (P less than 0.05). IA rt-PA provides a more effective, safer fibrinolytic regimen than conventional therapy with Sk. IV rt-PA has not been as successful and carries a significantly higher risk of haemorrhagic complications. PMID- 1913124 TI - Infra-inguinal aneurysms: outcome for patient and limb. AB - The outcome of conservative treatment of infra-inguinal (femoral and popliteal) aneurysms was compared with that following vascular reconstruction. Over a 12 year period up to December 1988, 43 femoral aneurysms and 35 popliteal aneurysms presented to the Oxford Regional Vascular Service; 88 per cent of the femoral and 60 per cent of the popliteal aneurysms were treated by vascular reconstruction. The outcome was assessed in terms of limb symptoms or preservation and patient survival at the most recent point of follow-up (median 4.5 years). At least 12 of the 13 initially asymptomatic femoral and popliteal aneurysms which were untreated remained asymptomatic. In contrast, six of the 26 limbs with asymptomatic femoral aneurysms and three of the 11 limbs with asymptomatic popliteal aneurysms developed significant distal ischaemia after vascular reconstruction; four limbs came to amputation after intervention. Aggressive surgical management of all asymptomatic infra-inguinal aneurysms is unjustified and dangerous. PMID- 1913125 TI - Observed incidence of paraplegia after infrarenal aortic aneurysm repair. PMID- 1913126 TI - Pharmacodynamics and pharmacokinetics of flunixin in the cat. AB - The non-steroidal anti-inflammatory agent (NSAID) flunixin was administered as single doses both orally and intravenously to six cats at a dose rate of 1.0 mg/kg in a two-part cross-over study. After oral dosing rapid absorption to a mean peak concentration of 2.586 micrograms/ml occurred at a mean time of 1.33 h. Similar mean plasma concentration-time AUC values for oral and intravenous dosing indicated that absorption by the former route was virtually complete. The decline in plasma concentration occurred fairly rapidly with both routes, and elimination half-life was approximately 1.0-1.5 h. The time course of inhibition of serum TXB2 concentration was similar for the two routes of administration, suggesting that similar dosing schedules are likely to be appropriate for evaluation of flunixin in clinical trials. PMID- 1913127 TI - The pharmacology of flukicidal drugs. PMID- 1913128 TI - Changes in the somatosensory evoked potentials and spontaneous electroencephalogram of hens during stunning in argon-induced anoxia. AB - This study examined the time to loss of consciousness in hens during stunning in argon-induced anoxia. Somatosensory evoked potentials (SEPs) and the spontaneous electroencephalogram (EEG) were recorded in 12 culled hens prior to and during stunning in less than 2% oxygen (air displaced by argon). An additional 20 hens were stunned with a similar concentration of oxygen and the time to loss of posture, eye closure, and the onset and duration of clonic and tonic convulsions were recorded. A further 10 hens were immersed in less than 2% oxygen for 15-17 s and their response to comb pinching was tested as soon as they had been transferred to atmospheric air. It is concluded that the birds had not lost the primary response in their SEPs by the time they started convulsing, but the reduction in the amplitude of the SEPs, changes in their spontaneous EEG and a negative response to comb pinch before the start of the convulsions indicated that the birds were unconscious when they convulsed. PMID- 1913129 TI - Blood biochemical reference ranges for sows under modern management conditions. AB - Published reference ranges for blood biochemistry in swine generally do not relate to sows in modern breeding units, and results were often obtained by methods that are now outdated. The ranges widely used in clinical practice reflect these inappropriate sources. The data presented here were obtained using modern methods of analysis on blood samples from healthy, conventionally managed sows from six breeding herds of known disease status in eastern England, and thus represent appropriate ranges for this class of swine. The values differ from earlier reports principally in higher values for total bilirubin, creatine kinase, and more particularly of total plasma and serum proteins. The latter are shown to be due to higher immunoglobulin concentrations than those previously reported. PMID- 1913130 TI - Gluconeogenesis from propionate produced in the colon of the horse. AB - The production of propionate has been measured in the large colon of two ponies fitted with cannulas and fed on a standard diet of hay or hay and wheat bran. A continuous infusion of 14C-labelled sodium propionate was made into a cannula in the right ventral colon and samples of ingesta were obtained from another cannula near the end of the right dorsal colon. A simultaneous intravenous infusion of [2 3H]-labelled glucose was made to measure total glucose entry. Colonic propionate production on the hay diet was 146 (range 110-176) mg/h per kg body weight and, on the hay and bran, 195 (range 130-273) mg/h per kg body weight. Mean total glucose production for the two diets was 120 (range 98-143) and 92 (range 79-116) mg/h per kg body weight, respectively. The results obtained indicate that 50% of the glucose was synthesized from propionate produced in the colon in ponies on the hay diet and 61% in ponies on the hay and bran diet. PMID- 1913131 TI - High performance liquid chromatographic determination of trimethoprim residues in egg yolk and albumen in a feeding experiment. AB - In a feeding experiment, the residues of trimethoprim (TMP) in egg yolk and albumen were determined by high performance liquid chromatography (HPLC). Laying hens were divided into four groups. The first group was designated as control and fed with TMP free diet during the experimental period. The second, third and fourth groups were administered with the feeds containing 4 p.p.m., 16 p.p.m. and 56 p.p.m. TMP, respectively, for 19 days and, thereafter, fed with TMP free diet. TMP was mainly found in yolk in all the three administered levels. In the medication period, the average concentration of TMP in the yolk of the second, third and fourth groups was 0.05, 0.25, and 0.90 p.p.m., respectively. After withdrawal of medication, the residues of TMP in yolk in the second, third and fourth groups decreased below the detection limit at 0.02 p.p.m. on days 4, 9, and 11, respectively. PMID- 1913132 TI - Isolation of Pasteurella haemolytica from the nasal cavity of goats. AB - Twenty transport-stressed goats were divided into two groups. The first group was further stressed with steroid. Pasteurella haemolytica was found at various sites in the nasal cavity of goats in this group as early as 2 weeks post transportation. The successful isolations continued consistently with more goats having pure growth of P. haemolytica at later stages. Mild catarrh rhinitis, loss of epithelial cilia and erosions were the main lesions observed in the nasal cavity. Goats in the second group that were not given steroid injections had inconsistent bacterial isolation and less severe pathological lesions. PMID- 1913133 TI - A survey of antimicrobial resistance in Salmonellae isolated from animals in England and Wales during 1984-1987. AB - Resistance to 14 antimicrobial substances was tested in 18,647 salmonella strains isolated from animals, their environment and from animal feeds during the period 1984-1987. Of the 2284 Salmonella dublin strains the percentage sensitive to all the antimicrobial substances ranged from 18.1 to 26.8. Resistance to the higher concentration of streptomycin (S25) ranged from 1.9 to 6.4%, whereas the corresponding figures when the lower concentration (S10) was used were 32.3 and 63.8%. Resistance to the higher sulphonamide concentration (Su500) never exceeded 3.3%, although in 1987 70.3% of strains showed resistance to the lower concentration. In general, less than 1% of strains showed resistance to the other antibacterial substances. No strains resistant to amikacin (AK), apramycin (Apr), gentamicin (CN) and colistin (CT) were detected. Of the 8677 S. typhimurium strains the percentage sensitive to all the antimicrobial agents ranged from 6.6 in 1985 to 13.6 in 1987. Resistance to tetracycline (T), ampicillin (PN), trimethoprim (TM) and chloramphenicol (C) ranged from 36.5 to 58.8%, the highest percentages being detected with tetracyclines. Less than 1% of strains showed resistance to furazolidone and none was resistant to amikacin and colistin. Resistance to apramycin ranged from 3.1% in 1984 to 11.6% in 1985; the figures for gentamicin were approximately half that of apramycin. In 1984, 41.6% of strains showed resistance to neomycin but only 8.5% in 1987. The fall in neomycin resistance was associated with the epidemic spread of the commonest phage-type DT204C becoming sensitive to neomycin. Of the 7687 strains of serotypes other than S. typhimurium and S. dublin the percentage sensitive to all antimicrobial agents ranged from 23.7 in 1985 to 14.7 in 1987. Resistance to tetracyclines and sulphonamides (Su500) ranged from 5.2 to 12.1% and 5.8 to 13.3% respectively. Resistance to the other antimicrobial agents was usually less than 5%. PMID- 1913134 TI - The equine rhabdomyolysis syndrome in the United Kingdom: epidemiological and clinical descriptive information. AB - The paper provides some basic epidemiological and clinical descriptive information for the equine rhabdomyolysis syndrome (ERS) in the United Kingdom. Information was obtained retrospectively from laboratory submission data as well as cases investigated by the author via their veterinary surgeon. Sex appeared to be a significant variable, with females being more likely than males to suffer from ERS compared to other conditions (P less than 0.01). More samples were submitted in the period November-February than at other times of the year (P less than 0.01). The condition appeared to be found in many breeds/types. Most episodes occurred whilst animals were being worked, although 38% occurred after exercise. In the majority of instances the affected animal was still able to walk. A clinical description of a very mild, mild, moderately severe and severe case of ERS is given. Utilizing all the information the syndrome was divided into five grades according to the severity of the stiffness and the presence or absence of auxiliary signs such as sweating and discoloured urine. PMID- 1913136 TI - Preliminary results on the effects of diazepam on physiological responses to transport in male goats. AB - Diazepam given i.v. to goats at 0.2 mg/kg body wt suppressed transport-induced hypercortisolaemia, hyperglycaemia, tachypnoea and tachycardia. A rebound increase in cortisol concentrations, respiratory and heart rates was seen during the recovery period after sedation. PMID- 1913135 TI - Abomasal foreign body and left-sided displacement in a pregnant cow. AB - By percussion left displaced abomasum (LDA) was identified in a 7-month pregnant Ayrshire cow which had presented with progressive abdominal distension despite a 5-day history of inappetence. An explorative laparotomy was performed and extensive fibrinous adhesions were identified between the abomasum, diaphragm and left abdominal wall. At the centre of these adhesions a 10 cm length of wire had penetrated the abomasal wall. Haematological analysis undertaken pre-surgery revealed a marked inflammatory response and profound disturbance of serum chloride and sodium concentrations. Following surgical correction of the LDA and intensive supportive therapy the cow made an uneventful recovery. PMID- 1913137 TI - The Mongolian gerbil as laboratory animal for testing the potency of Leptospira antisera. PMID- 1913138 TI - Retinofugal and retinopetal projections in the green sunfish, Lepomis cyanellus. AB - The retinofugal and retinopetal connections in the green sunfish were studied by autoradiographic and horseradish peroxidase methods. All retinofugal fibers decussate in the optic chiasm. Some fibers project to contralateral preoptic and hypothalamic nuclei while others recross to project to the comparable ipsilateral nuclei. Contralaterally, the medial optic tract projects to the periventricular thalamic and pretectal nuclei and, sparsely, to the rostral optic tectum. The dorsal optic tract projects to the parvocellular portion of the superficial pretectal nucleus, the central pretectal nucleus, nucleus corticalis, and the rostral portion of the optic tectum. The ventral optic tract primarily projects to the caudal portion of the optic tectum, giving off fibers in route to innervate various nuclei, including the parvocellular superficial pretectal nucleus and the dorsal and ventral accessory optic nuclei. The axial optic tract projects to the dorsal accessory optic nucleus, the central pretectal nucleus, and the caudal optic tectum. Retinal fibers reach the ipsilateral thalamus, pretectum and other sites via a redecussation through the posterior commissure. From outgroup analysis it is concluded that such redecussating fibers are an independently derived character within actinopterygians and are homoplasous to nondecussating ipsilateral retinal projections in other vertebrates. Neurons retrogradely labeled with horseradish peroxidase were found to form a rostrocaudal column from the olfactory bulb and nerve through the ventral telencephalon to caudal diencephalic levels along the medial aspect of the optic tract. It is possible that all these neurons consist of one population of migrated ganglion cells of the nervus terminalis. PMID- 1913139 TI - Motor neurons and motor columns of the anterior spinal cord of salamanders: posthatching development and phylogenetic distribution. AB - The posthatching development of rostral (1st-4th) spinal motor neurons was studied in ten species of salamanders, using horseradish peroxidase and cobaltic lysine tracing techniques. Development of spinal motor neurons differs among species in association with differences in life history and general developmental patterns (i.e., between species with aquatic larvae versus those with direct development, with or without ontogenetic repatterning). In the plesiomorphic state, represented by species with aquatic larvae, five types of motor neurons are present: (1) large, multipolar neurons, believed to be primary motor neurons; (2) medial, pear-shaped neurons; (3) larger, spindle-shaped neurons, which increase in number during posthatching development; (4) cone-shaped neurons, and (5) bilaterally arborizing neurons (found only at the rostral pole of the first spinal nucleus). Direct-developing desmognathine salamanders have the plesiomorphic set of motor neurons, but appear to lack Mauthner neurons. Direct developing plethodontine salamanders have cone-shaped, pear-shaped, and spindle shaped neurons, but lack primary motor neurons and Mauthner neurons. Direct developing bolitoglossine salamanders, which exhibit both pedomorphosis and ontogenetic repatterning, have only medial, pear-shaped neurons, and lack primary motor neurons, spindle-shaped neurons, cone-shaped and bilaterally arborizing neurons. At all developmental stages in all species studied, pear-shaped neurons are always found in medial positions and spindle-shaped neurons are always found in lateral positions. Spindle-shaped neurons are found more laterally as development proceeds. The medial and lateral motor columns of salamanders and amniotes differ in their connections with peripheral targets (i.e., axial muscles vs. limbs). This implies a lack of homology of neuron types in salamanders and amniotes, which has been obscured by the current terminology. PMID- 1913140 TI - Alzheimer amyloid beta/A4 peptide binding sites and a possible 'APP-secretase' activity associated with rat brain cortical membranes. AB - We carried out ligand binding experiments on membranes from rat brain cortical grey matter using radioiodinated beta/A4 8-17, with non-specific binding determined by the addition of 10 microM unlabelled peptide. Specific, reversible binding amounted to 60-75% of total binding and showed a clear dependence on time, temperature, pH and membrane concentration. Kinetic analyses indicated a high-affinity binding site with an apparent KD of 440 pM. However, the ligand was partly degraded with loss of the Ser8, Lys16 and Leu17 residues. Excision of the two C-terminal amino acids was inhibited by EDTA, EGTA, dithiothreitol or Zn2+ but was stimulated by Ca2+ or Mn2+. These studies demonstrate high-affinity binding sites for beta/A4 8-17 (or its derivatives) in rat brain, suggesting that this region may contain a physiologically important amino acid sequence and identify a potential membrane-associated amyloid precursor protein (APP) secretase activity. PMID- 1913141 TI - Acetylcholine receptor channel gating and conductance involve extracellular disulfide bond(s). AB - Disulfide bonds are critical determinants of the function of the acetylcholine receptor at the vertebrate neuromuscular junction. In the present study, the role of these bonds in acetylcholine receptor channel gating and conductance was investigated at the single channel level. Disulfide bond reducing agents decreased the single channel conductance of both ligand-gated and spontaneously opening acetylcholine receptor channels, indicating that the observed decrease in conductance is not due to blockade of the channel lumen by agonist molecules. In addition, the reducing agents increased the opening frequency of both liganded and unliganded acetylcholine receptor channels. Use of inside-out patches and both membrane permeant and impermeant reducing agents demonstrated that the disulfide bonds involved are all extracellular. These findings indicate that both channel gating and conductance involve conformational changes in extracellular regions of the acetylcholine receptor. PMID- 1913142 TI - Amygdala and dorsal hippocampus lesions block the effects of GABAergic drugs on memory storage. AB - These experiments examined the effects of posttraining systemic administration of the GABAergic agonist muscimol and the GABAergic antagonist bicuculline on retention in mice with bilateral lesions of the amygdala, dorsal hippocampus or caudate nucleus. Unoperated male CD1 mice and mice with either sham lesions or electrolytically induced lesions of these 3 brain regions were trained in a one trial inhibitory avoidance task and, immediately after training, received i.p. injections of either muscimol, (1.0, 2.0 or 3.0 mg/kg), bicuculline, (0.25, 0.5 or 1.0 mg/kg), or control solutions. Retention was tested 24 h after training. Lesions of the 3 brain regions produced comparable impairment of retention. In the unoperated controls and sham controls muscimol and bicuculline produced dose dependent impairment and enhancement, respectively, of retention. The drug effects on retention were blocked by lesions of the amygdala and hippocampus, but were not blocked by lesions of the caudate nucleus. These findings are consistent with other recent evidence suggesting that the amygdala and hippocampus are involved in mediating posttraining neuromodulatory influences on memory storage. PMID- 1913143 TI - Intracellular response of caudate neurons to variable frequency stimulation of motor cortical areas in dog. AB - The intracellular response to electrical stimulation of motor cortex was studied in 77 neurons recorded in the head of the caudate (Cd) nucleus of dog. Single pulse stimulation of either medial, intermediate or lateral precruciate cortex produced a response in 69 neurons, 59% of which responded to more than one cortical area. Most intracellular responses were complex potentials consisting of an initial depolarization (E) followed by a longer duration hyperpolarization (I) or E-I response complex. When stimulated with trains of low frequency pulses (10 Hz), the stimulus-generated I potentials reduced the absolute amplitude of the evoked E's, often to a level below resting potential. However, at higher frequencies (50 Hz), the I potentials were attenuated and the E potentials summated into a prolonged depolarization lasting the duration of the stimulus train. A computer model of the response to multiple stimuli was generated assuming that the E-I response to each stimulus pulse in the train should temporally summate with previous responses. As the frequency of stimulation was increased, this model consistently predicted greater summation of the I potentials than was experimentally observed. These data suggest that inhibition of Cd neurons is input frequency dependent such that as the frequency of cortical input increases there is a decrease of input-generated inhibition of Cd neurons. Thus, inhibition may modulate the response of Cd neurons such that cortical input must reach a critical firing frequency before being relayed through the Cd nucleus. PMID- 1913144 TI - Prenatal stress alters sexually dimorphic nuclei in the spinal cord of male rats. AB - The spinal nucleus bulbocavernosus (SNB), the dorsolateral nucleus of the spinal cord (DLN), and the bulbocavernosus/levator ani (BC/LA) muscle complex were examined in prenatally stressed and control adult male rats, which had been screened for male copulatory behavior. There was a small but significant decrease in the number of DLN (5%) and SNB (3%) neurons in prenatally stressed males compared to controls. Prenatal stress had no effect on the somal or nuclear area of individual neurons within either nucleus, nor did it affect the weight of the BC/LA muscle complex. There were no differences in any of these measures between males that ejaculated and those did not in either the stressed or the control group. These data suggest that exposure of pregnant rats to transient environmental stressors may result in permanent alterations in androgen-sensitive CNS structures in their male offspring. PMID- 1913145 TI - Differential sensitivity to hypoxia of the peripheral versus central trajectory of primary afferent axons. AB - Myelinated primary afferent fibers have both peripheral and central nervous system components. As the fibers course through peripheral nerve and dorsal roots they are myelinated by Schwann cells, but after they invade the spinal cord they become myelinated by oligodendrocytes and have associations with astrocytes. This presents the opportunity to compare the pathophysiology of PNS (Schwann cell associated) vs. CNS (oligodendrocyte/astrocyte-associated) portions of the same axonal trunk located in the dorsal roots and dorsal columns, respectively. Dorsal spinal roots and slices of dorsal columns isolated from adult rats were studied in a sucrose gap chamber from which compound action potential and membrane potential changes could be recorded. The results indicate that the peripheral component of the afferent fibers is resistant to hypoxia as evidenced by stable action and membrane potential when O2 in the bathing medium was completely replaced with N2 for periods up to 2 h. In contrast, the axons become sensitive to hypoxia as they project through the dorsal columns as evidenced by rapid reduction in action potential amplitude accompanied by membrane depolarization when O2 is replaced by N2. This differential response to hypoxia, observed on the same axon branches but over CNS vs. PNS trajectories, suggests that differences related to the extracellular environment or in axo-glial organization in dorsal root vs. dorsal column may confer different degrees of susceptibility to anoxia. PMID- 1913146 TI - The wobbler mouse: amino acid contents in brain and spinal cord. AB - Reductions in glutamate and aspartate contents, together with increased contents of taurine, have been observed in the autopsied brains and spinal cords of patients who have died with amyotrophic lateral sclerosis (ALS). The wobbler mouse develops an inherited degeneration of motoneurons within the brainstem and spinal cord, and has been proposed as an animal model of ALS. In symptomatic wobbler mice we found brain contents of glutamate, aspartate, and taurine similar to those in unaffected littermates, while brain contents of glutamine were increased, and those of serine and alanine were decreased. Spinal cords of wobbler mice had slightly decreased contents of glutamate, aspartate and glycine compared to normal littermates. Abnormalities of amino acid contents in the nervous system of wobbler mice are dissimilar to those in ALS patients suggesting a different pathogenesis of motoneuron loss. PMID- 1913147 TI - Glucose transport is reduced in the blood-brain barrier of aged rats. AB - To determine the biochemical basis of decreased brain uptake of glucose with age, the brain influx of 3-O-methylglucose (3-O-MG) was measured in male Fischer 344 rats at various ages using the arterial injection-tissue sampling technique of Oldendorf. The Vmax of 3-O-MG transport in the 24-month-old rats (0.22 +/- 0.14 mumol/min/g) was significantly lower than that in 3-month-old rats (0.88 +/- 0.18 mumol/min/g) (P less than 0.05). The Km of transport in aged rats (10.1 +/- 4.8 mM) was not different from that in young rats (8.1 +/- 2.5 mM). The cytochalasin B binding sites in cerebral microvessels isolated from aged rats (13.9 +/- 0.9 pmol/mg) compared to the binding sites in cerebral microvessels of young rats (21.9 +/- 1.4 pmol/mg) were significantly reduced (P less than 0.001). However, the immunoreactive mass of glucose transporter of cerebral microvessels was not altered with age. The enrichment of capillary preparations with gamma-glutamyl transpeptidase activity, a marker of endothelial cells, was not altered in aged rats, suggesting that the reduced blood-brain barrier transport of glucose is due to specific reduction in glucose binding sites of the transporter rather than secondary to a non-specific age-related effect of endothelial cell drop-out. PMID- 1913148 TI - Saccade onset and offset lambda waves: relation to pattern movement visually evoked potentials. AB - The lambda (lambda) wave is an occipital EEG potential which occurs when saccadic eye movements are made against an illuminated contrast background. There is some disagreement concerning the presence of sub-components to the lambda-wave, and its relationship to visually evoked potentials. In the present study, lambda waves were recorded with saccades of different durations (30-110 ms) and compared to VEPs associated with pattern movements of similar durations and velocity. It was found that the lambda-wave consisted of a saccade onset component with positive sub-components at 59 and 100 ms after saccade onset, and a saccade offset component with a positive potential at 74 ms after saccade offset. With small saccades of 30 ms duration or less, these components superimposed to form a single lambda-wave. In the case of pattern movement VEPs, a movement onset component of latency 110 ms following movement onset, and a movement offset component at 89 ms after movement offset, were identified. The similar behaviour of the lambda-wave and VEP under these conditions supports the view that the lambda-wave is a visually evoked potential resulting from movement of the visual field across the retina during a saccadic eye movement. PMID- 1913149 TI - Phenytoin and retinal spreading depression. AB - Several studies indicate that spreading depression is fundamentally related to seizure marches and to the aura of classical migraine. Moreover, recent investigations call attention to its possible relevance in clinical disturbances associated with brain ischemia, trauma, and hypoglycemia. The anticonvulsant phenytoin has been shown to protect the nervous tissue from the effects of anoxia and ischemia. These properties suggest that phenytoin should be able to counteract spreading depression. Therefore, we investigated its effect on spreading depression elicited by mechanical or chemical (KCl) stimulation, in isolated chick retinas. The results showed that phenytoin: (1) increases the threshold concentration of KCl to initiate the phenomenon; (2) decreases the velocity of propagation of spreading depression; (3) shortens considerably the duration of the slow potential, ionic (K+, Ca2+, Cl-), and volume changes of the extracellular compartment during spreading depression. Possible mechanisms underlying the observed effects are discussed. PMID- 1913150 TI - Repair of the blood-brain barrier following implantation of polymer capsules. AB - Past studies of polymer-encapsulated cell lines implanted in the brain indicated their usefulness for transmitter replacement therapy in animal models. Such grafts may have potentially important clinical applications, but their placement into neural parenchyma may cause a traumatic injury resulting in a leaky blood brain barrier around the implant. This study investigated whether or not injury repair and reformation of the barrier takes place near a polymer capsule implanted in the brain of Sprague-Dawley rats. The two methods used for detection of a leaky barrier were immunocytochemical localization of extravasated serum albumin and circulating Evans blue that binds to serum albumin. Immunocytochemical staining for glial filament protein provided a measure for evaluating injury associated gliosis. Polymer capsules implanted for 10, 16 and 18 days were surrounded by microvessels that leaked detectable quantities of serum albumin into interstitial spaces and, by secondary uptake, into some nearby neurons and reactive astrocytes. Reactive astroglia were observed within the outer regions of the capsule wall and in the near vicinity of the implant after these early survival times. In contrast, at post-implantation times of 46 and 54 days, serum albumin was no longer detected in the neural parenchyma near the macrocapsules and only few reactive astrocytes remained. These findings show that polymer capsules implanted within the cerebrum permit (a) reformation of the blood-brain barrier and (b) occurrence of repair processes that lead to minimal deposition of reactive astroglia near the implanted polymer capsule. PMID- 1913151 TI - Terminal excitability of the corticostriatal pathway. I. Regulation by dopamine receptor stimulation. AB - Glutamatergic cortical and dopaminergic nigral afferents converge onto neurons of the neostriatum forming synapses in close proximity. Studies, mainly using pharmacological methods, suggest presynaptic interactions between these afferents. The influence of dopaminergic transmission on the cortical terminal fields in the striatum was assessed electrophysiologically using the terminal excitability method. Antidromic action potentials recorded from neurons in the prefrontal cortex were elicited by bipolar electrical stimulation (250 microns wire, 0.5 mm tip separation) of the cortical terminal field in the contralateral dorsomedial neostriatum. Threshold excitability was defined as the minimum current sufficient to elicit 95-100% antidromic response on non-collision trials. Under control conditions, the mean threshold current was 1.7 +/- 0.2 mA. Drugs were applied in a volume of 312 nl delivered over 5 min to the striatal stimulation site. Following local striatal administration of amphetamine (10 microM) or electrical stimulation of the nigrostriatal pathway (1-2 pulses, 1.5 mA/0.5 ms/1 Hz) an increase in striatal stimulating current was required in order to reinstate threshold levels of antidromic response. This decrease in the excitability of corticostriatal afferents could be reversed by local infusion of haloperidol (1 microM) or L-sulpiride (10 nM) and did not occur following depletion of dopamine stores with alpha-methylparatyrosine and reserpine. The possible participation of postsynaptic dopamine receptor stimulation was ruled out as these effects were still seen in animals with kainic acid induced lesions of the striatum. In addition, terminal excitability was not modified by the muscarinic agonist carbachol (10 microM). Striatal administration of apomorphine (10 microM) decreased terminal excitability similar to amphetamine. The specific D-2 agonist, quinpirole (10-20 microM) did not affect excitability. These results indicate that manipulations which have been shown to increase the release of endogenous dopamine decrease the excitability of prefrontal corticostriatal afferents by stimulation of presynaptic dopamine receptors which are insensitive to low doses of quinpirole but sensitive to L-sulpiride and apomorphine. The mechanisms underlying dopamine-induced changes in terminal excitability are likely to be similar to those which have been shown to alter conductance at postsynaptic sites. PMID- 1913152 TI - Opioid modulation and sensitization of dopamine release elicited by sexually relevant stimuli: a high speed chronoamperometric study in freely behaving rats. AB - High speed chronoamperometry was used to measure oxidation and reduction currents associated with monoamine release in the caudate putamen and nucleus accumbens of freely moving rats exposed to bedding from cages that housed other male, ovariectomized female, or estradiol-progesterone-primed female rats. Estrus female, but not male or ovariectomized female bedding potently increased the electrochemical signal from electrodes implanted within the nucleus accumbens, and less effectively from more dorsal sites. Naloxone pretreatment attenuated the increase in the electrochemical signal. Repeated exposure to estrus female bedding led to an increased, or sensitized, response within the nucleus accumbens that was also sensitive to naloxone pretreatment. The ratios of the reduction to oxidation currents indicated that dopamine was the principal contributor to the increase in the electrochemical signal, suggesting that activation of the mesolimbic dopamine system accompanies exposure to sexually relevant stimuli. These results suggest that the facilitation of sexual behaviors by dopamine may be due, at least in part, to the processing of incentive motivational cues, and not necessarily to effects on copulation, itself. The results of the present study also suggest that opioid peptides contribute to the activation of mesolimbic dopamine by sexually relevant olfactory stimuli. PMID- 1913153 TI - Reinnervation of denervated skeletal muscle by central neurons regenerating via ventral roots implanted into the spinal cord. AB - The reinnervation of denervated skeletal muscle by central axons regenerating via a ventral root implanted into the spinal cord was examined in rats. The 8th thoracic ventral root was severed and its distal end implanted into the ventro lateral column of the spinal cord via a stab incision. In control animals the root was severed, but was not implanted into the stab incision. After 12-14 months the animals were examined electrophysiologically to determine the presence or absence of motor units in the 8th intercostal muscle which were reinnervated by centrally derived axons regenerating via the implant. Such units were found in implanted animals, but in none of the controls. Evidence that the motor units were reinnervated by central axons included the facts that the units could be activated either, (1) reflexly (i.e. trans-synaptically) by electrical stimulation of the dorsal roots or spinal cord, or (2) pharmacologically by either the intraspinal injection of glutamate or acetycholine, or by the systemic administration of strychnine. Great care was taken to ensure that the only feasible connection between the spinal cord and the 8th intercostal muscle was via the site of implantation. The EMG signals from the motor units were of large amplitude, typical of reinnervated muscle, and their individual activation resulted in discernible contractions of regions of the T8 intercostal muscle. We conclude that regenerating CNS neurons can be guided to innervate denervated skeletal muscle by the implantation of severed ventral roots into the spinal cord. The neuromuscular synapses formed are functional and persistent. The findings may be relevant to the restoration of function after nervous injuries, such as the avulsion of ventral roots. PMID- 1913154 TI - Changes in inhibitory processes in the hippocampus following recurrent seizures induced by systemic administration of kainic acid. AB - Rats were chronically prepared with stimulation electrodes in the angular bundle and recording electrodes in the dentate gyrus under electrophysiological guidance. Following testing of dentate gyrus field potentials, the animals were given a single injection of kainic acid which caused repeated seizures and led to status epilepticus. The seizures were stopped by administration of a barbiturate anesthetic after 60 min. Changes in inhibition during seizure development were monitored by administering pulse pairs at regular intervals. The results revealed a progressive kainic acid-induced loss in inhibition that preceded the occurrence of seizures. This breakdown of inhibition was transient, and generally disappeared within 24 h. Over subsequent testing, recurrent inhibition, as measured by the double pulse test, increased beyond baseline levels. This increase persisted for at least one month and was restricted to the early phase of inhibition with a conditioning/test pulse interval of less than 50 ms. A later phase of inhibition, measured at interpulse intervals between 200 and 300 ms, showed a transient decrease which lasted about a week. These results contrast with previous reports of a long-term period of hyperexcitability following recurrent seizures. Procedural differences which might account for such discrepancies are discussed. PMID- 1913155 TI - Controllable and uncontrollable footshock and monoaminergic activity in the frontal cortex of male and female rats. AB - Effects of controllable and uncontrollable footshock on monoaminergic activity in the frontal cortex and plasma corticosterone levels were studied in male and female rats. Subjects were exposed to a shuttle-box procedure for a period of either 30 min (60 shocks) or 90 min (180 shocks). A shuttle response ended shock presentation for escape subjects, whereas their yoked, same-sex, counterparts were unable to escape from shock presentation. A third group was exposed to the experimental environment, but did not receive any shocks. Concentrations of noradrenaline, serotonin and dopamine and their major metabolites were measured in the frontal cortex by high performance liquid chromatography with electrochemical detection. Plasma corticosterone was measured by radioimmunoassay. Results of this experiment show that: (1) exposure to the experimental environment without shock already increased the activity of all 3 transmitter systems. In particular, serotonin was very responsive to mere confinement to the shuttle-box. Changes induced by exposure to the experimental environment were similar for males and females. (2) Presentation of footshocks further increased transmitter activity. The activation of noradrenaline and dopamine was larger after uncontrollable shock than after controllable shock. Moreover, uncontrollable shock resulted in higher serotonin levels than controllable shock. (3) Sex-dependent effects of controllability were found for noradrenaline and dopamine, but not for serotonin. Differences in catecholaminergic activity between controllable and uncontrollable shock were larger in females than in males. (4) In both males and females, corticosterone levels in plasma were increased by exposure to the experimental environment. A further elevation was found in response to footshock presentation, which was independent of the controllability of shock. PMID- 1913156 TI - Are the post-inspiratory neurons in the decerebrate rat cranial motoneurons or interneurons? AB - We examined the membrane potentials of 63 respiratory neurons in the ventrolateral medulla of decerebrate rats, whose trajectories had the characteristics of the post-inspiratory neurons, i.e. exhibiting hyperpolarization during inspiration, rapid depolarization at end-inspiration and progressive repolarization with a decrementing pattern during the intervals between phrenic bursts. Synaptic responses of 6 post-inspiratory neurons which were tested by stimulation of cervical vagus or superior laryngeal nerves were excitatory. Eleven of these 63 post-inspiratory neurons were labeled by intracellular injection of horseradish peroxidase (HRP). Ten of these 11 labeled neurons were motoneurons since their axons exited the medulla after joining the roots of cranial nerves. However, only one of these motoneurons was antidromically activated by stimulation of the ipsilateral cervical vagus nerve. We assumed that most of the post-inspiratory medullary neurons of the present study were motoneurons, but not interneurons, although antidromic invasion was not possible after stimulation of the cervical vagus and superior laryngeal nerves. Two post-inspiratory neurons of this sample had bulbospinal axons, which were revealed by antidromical activation of spinal cord and HRP labeling, respectively. The axon of the labeled bulbospinal neuron had axonal collaterals which were distributed within the region of the nucleus ambiguous of the ipsilateral medulla. The functional significance of this type of post-inspiratory neuron is discussed. PMID- 1913157 TI - A conditioned stimulus decreases extracellular dopamine in the nucleus accumbens after the development of a learned taste aversion. AB - The conditioned taste aversion (CTA) paradigm and microdialysis were used to determine if extracellular dopamine in the nucleus accumbens is related to the reward value of a stimulus. Intraorally applied saccharin caused a 37% increase in DA in naive rats and a 40% decrease in subjects with a CTA to this taste. These results suggest that accumbens DA is not just a function of arousal but is related to stimulus reward. PMID- 1913158 TI - FCCP releases Ca2+ from a non-mitochondrial store in an identified Helisoma neuron. AB - The proton ionophore FCCP was evaluated for use as a selective blocker of mitochondrial Ca2+ sequestration in identified Helisoma neurons in vitro. By use of the Ca2+ indicator fura-2, it was found that application of FCCP evoked a gradual increase in cell body [Ca2+]i that reached a level approximately 3-fold higher than baseline after 60 min. Moreover, FCCP released Ca2+ even when added after mitochondrial stores of Ca2+ had previously been emptied by an alternate method. From these and other experiments, it is concluded that FCCP, in addition to its recognized effect on mitochondrial Ca2+ sequestration, also releases Ca2+ from a non-mitochondrial store and is, therefore, unsuitable for use in an intact neuron to selectively inactivate mitochondrial Ca2+ uptake. PMID- 1913159 TI - Norepinephrine-stimulated phosphatidylinositol metabolism in genetically epilepsy prone and kindled rats. AB - Genetically epilepsy-prone rats (GEPR-9) and kindled rats have reduced noradrenergic function. In the present study, norepinephrine-stimulated accumulation of inositol phosphates was reduced in cerebral cortex of GEPR-9 and kindled rats when compared to control and non-kindled rats, respectively. No such reduction was found in amygdala/pyriform cortex and hippocampus. These results support the hypothesis that cortical noradrenergic and associated second messenger systems are impaired in epilepsy. PMID- 1913160 TI - Buffy coat from families of Alzheimer's disease patients produces intracytoplasmic neurofilament accumulation in hamster brain. AB - Buffy coat of three members from a family with Alzheimer's disease was inoculated into hamster brains. Eighteen months after the inoculation, all experimental animals were sacrificed for the neuropathological study. Hematoxylin-eosin staining showed no gross vacuolar degeneration, or neuronal loss in the cortex. The spongiform degeneration was minimum. Immunostaining with antibodies against neurofilament 200 kDa subunit protein revealed massive immuno-positive intracytoplasmic inclusion bodies within neurons of the brainstem nuclei. By electron microscopy, the intracytoplasmic inclusion body was shown to be composed of proliferated 10 nm neurofilaments. The intra-cytoplasmic neurofilament proliferation was observed with the hamsters inoculated with the buffy coat from Alzheimer's disease patients as well as an apparently normal member of the family. PMID- 1913161 TI - Effect of apamin, a toxin that inhibits Ca(2+)-dependent K+ channels, on learning and memory processes. AB - Apamin, a neurotoxin extracted from bee venom, specifically binds to a particular class of Ca(2+)-activated K+ channels which are involved in the slow afterhyperpolarization (S-AHP) that follows action potentials in many excitable cells. We tested in mice the effects of apamin on learning and memory processes. The results showed that pre-training injection of apamin accelerated the acquisition of a bar-pressing response but also increased the bar-pressing rates of the animals. This latter result suggests that apamin accelerated acquisition because it increased behavioral activity in general and the number of bar-presses in particular. Post-training apamin injection retroactively and non-contingently facilitated memory processes taking place shortly after training in a bar pressing task. The lack of an effect of the delayed apamin injection showed that apamin did not act proactively on memory retrieval processes. These results suggest that apamin-sensitive KCa channels may contribute to memory processes. PMID- 1913162 TI - Response of cytosolic calcium to anoxia and cyanide in cultured glomus cells of newborn rabbit carotid body. AB - Microscopic fluorometry was used to examine the effects of anoxia and cyanide (CN ) on cytosolic calcium [Ca2+]i of cultured carotid body (CB) glomus cells from newborn rabbits. Applications of high K+ and veratridine (VRT), a sodium channel activator, induced rapid and marked increases in [Ca2+]i. These effects were inhibited by D600 a calcium channel blocker. [Ca2+]i changes induced by VRT were also blocked by tetrodotoxin (TTX). Glomus cells exhibited a slow increase in [Ca2+]i in response to anoxia and CN-, and a slight decrease during hyperoxia. The effects of anoxia and CN- were blocked by D600 but not by TTX. We conclude that these stimuli induce calcium entry into glomus cells via voltage-dependent Ca2+ channels. Voltage-dependent Na+ channels were not involved. PMID- 1913163 TI - Calcium channel blockers and excitatory amino acids. AB - The calcium channel blockers (CCB), diltiazem, verapamil and nifedipine, antagonize in mice both N-methyl-DL-aspartate- (NMDLA) and kainate-induced convulsions, which were not affected by carbamazepine and ethosuximide. The CCB, on the other hand, were ineffective against convulsions induced by bicuculline, pentylenetetrazol and electroshock. The results suggest that the CCB may be efficacious in the treatment of those neurodegenerative diseases putatively caused by the excitatory amino acids. PMID- 1913164 TI - Effects of hypoxia on fetal rat brain metabolism studied in utero by 31P-NMR spectroscopy. AB - An animal model of perinatal asphyxia, in which near-term fetal rats are subjected to-short periods of hypoxia, has been investigated by 31P-NMR spectroscopy. Changes in the high-energy phosphates and intracellular pH of the fetal rat brain were measured in utero following ligation of the placental blood vessels, and during reperfusion after a 20-min period of occlusion. The hypoxia induced changes observed in the fetal brain were substantially slower than in the adult, and were completely reversible after 20 min of hypoxia. PMID- 1913165 TI - Ethanol reduces vasopressin release by inhibiting calcium currents in nerve terminals. AB - Ingestion of ethanol (EtOH) is known to result in a reduction of plasma arginine vasopressin (AVP) levels in mammals. We examined the basis for this effect using a combination of biochemical and electrophysiological techniques. Release of AVP from nerve terminals isolated from the rat neurohypophysis was very sensitive to EtOH, with significant reductions in AVP release evident in 10 mM EtOH. However, EtOH did not affect the release of AVP from terminals which had been permeabilized with digitonin, suggesting that voltage-gated calcium channels might be the target of EtOH's actions. Patch clamping of these terminals indicated that both inactivating and long-lasting calcium currents were reduced in EtOH, but the long-lasting currents were more sensitive (significant reductions in 10 mM EtOH). EtOH-induced decreases in plasma AVP levels can be explained by EtOH's inhibition of calcium currents in the nerve terminals. PMID- 1913166 TI - Electrophysiological evidence that morphine can exert an antinociceptive effect in a neuropathic state: a study in the ventrobasal thalamus of rats after moderate ligation of one sciatic nerve. AB - This study was performed in rats with a mononeuropathy induced by loose ligatures around the common sciatic nerve 2 weeks before the recording session, and exhibiting clear alterations of several pain-related behaviours. Morphine injected intravenously (0.6 and 1 mg/kg) strongly depressed the ventrobasal thalamic neuronal responses to pinch applied to the lesioned or the non-lesioned hindpaw. The effect, comparable on the both sides, was dose-related and reversed by naloxone (0.1 mg/kg i.v.). PMID- 1913167 TI - A re-examination of enkephalin's coexistence with gamma-aminobutyric acid in amacrine cells of the larval tiger salamander retina. AB - Double-label immunocytochemistry was utilized to re-examine the colocalization of enkephalin and gamma-aminobutyric acid (GABA) in amacrine cells of the larval tiger salamander retina. A total of 465 enkephalin-immunoreactive amacrine cells were identified and in all cases these cells were GABA-immunoreactive. This finding corroborates a previous study that showed greater than 96% of enkephalin amacrine cells in the tiger salamander retina to specifically accumulate [3H]GABA and provides additional evidence for the GABAergic nature of these enkephalin amacrine cells. PMID- 1913168 TI - Commissural responses of rat retrohippocampal neurons. AB - Synaptic responses of commissurally activated rat subicular and entorhinal neurons were studied intracellularly in vivo by stimulating the contralateral dentate gyrus. The most prominent synaptic responses in both subicular and entorhinal neurons were inhibitory postsynaptic potentials (IPSPs). IPSPs were generated in combination with antidromic spikes and/or excitatory postsynaptic potentials (EPSPs) and orthodromic spikes. No dependency between any two response types were found. Commissurally projecting subicular neurons (identified by the presence of antidromic spikes evoked by contralateral stimulation) were found, extending previous anatomical studies. Commissurally projecting entorhinal neurons were found in layer II, confirming previous anatomical studies. Positive correlations between antidromic spike latency and depth of recording sites supported the interpretation that axons projected along the fiber bundles of the hippocampal commissures and angular bundle to distribute to their targets. Possible circuits that could have mediated the excitatory and inhibitory responses of these retrohippocampal neurons are considered. PMID- 1913169 TI - Amyloid beta/A4 protein precursor is widely distributed in both the central and peripheral nervous systems of the mouse. AB - We studied the immunocytochemical distribution of amyloid beta/A 4 protein precursor (APP) in both the central and peripheral nervous tissues of the mouse. We used two different antisera against the synthetic peptides corresponding to the carboxyl- and the amino-terminal regions of APP, which are common to all isoforms of APP (APP695, APP714, APP751 and APP770). Both antisera recognized the same 106-122 kDa proteins from the mouse brain on immunoblotting. Immunocytochemically, in cortical and subcortical areas, reactivities of both antisera were located in neurons of all sizes. Immunoreactive neurons were widely distributed showing no particular pattern. Various neuron types in the spinal cord were also immunoreactive. In the peripheral nervous system, ganglion cells and their processes showed immunostaining. Immunoreactivity was also seen in the astrocytes, oligodendroglia and ependymal cells widely distributed in the brain and spinal cord, mantle cells in the ganglia, and Schwann cells in peripheral nerves. These results indicated that the full length of APP is distributed in almost all neurons and some glial cells in the mouse central and peripheral nervous systems. PMID- 1913170 TI - Characteristics of activity-dependent potassium accumulation in mammalian peripheral nerve in vitro. AB - Ion-sensitive microelectrodes were used to study the behavior of extracellular ions in rat sciatic nerve during and following activity. Nerve stimulation produced increases in [K+]o that were dependent upon the frequency and duration of stimulation; no change in extracellular pH occurred with stimulation. Increases in [K+]o depended on axonal discharge since they were blocked by inhibiting sodium channels with tetrodotoxin. At 22 degrees C, stimulation could induce increases in [K+]o of several mM; at 36 degrees C, stimulation rarely produced increases in [K+]o greater than 1 mM. Stimulated increases in [K+]o dissipated very slowly (i.e. t 1/2 = 50-100 s) and the rate of dissipation was not significantly affected by anoxia, changes in temperature, changes in extracellular pH, or the application of a blocker of Na+, K(+)-ATPase (ouabain) or a K+ channel blocker (Ba2+). In comparison to the central nervous system, neural activity in rat sciatic nerve produced smaller increases in [K+]o and these increases dissipated much more slowly. The primary mechanism of K+ dissipation appeared to be diffusion, probably facilitated by the larger extracellular space in peripheral nerve compared to the central nervous system, but impeded by diffusion barriers imposed by the blood-nerve barrier. PMID- 1913171 TI - Purification of a nicotinic acetylcholine receptor from rat brain by affinity chromatography directed at the acetylcholine binding site. AB - We have purified a nicotinic acetylcholine receptor from rat brain by use of an acetylcholine affinity resin commonly employed for the purification of nicotinic acetylcholine receptor from electric tissue. Receptor, specifically eluted with nicotine, bound (-)-[3H]nicotine with a dissociation constant of approximately 21 nM. Binding was inhibited by carbamylcholine but not by alpha-bungarotoxin. Polyacrylamide gel electrophoresis yielded two protein bands, of apparent mol. wts. 80,400 and 52,400. These results provide independent confirmation of the subunit size and composition reported for rat brain nicotinic receptor isolated by immunoaffinity methods and demonstrate a method of purification that can be performed with commercially available reagents. PMID- 1913172 TI - Purification and characterization of endoproteases from human choroid plexus cleaving prodynorphin-derived opioid peptides. AB - An endoprotease converting the dynorphins and alpha-neoendorphin has been purified to apparent homogeneity from soluble extracts of human choroid plexus. The purified enzyme was stained as a single band after sodium dodecyl sulphate polyacrylamide gel electrophoresis with an apparent molecular weight of around 54,000 Da. The enzyme potently cleaves dynorphin A, dynorphin B and alpha neoendorphin at consecutive pairs of basic amino acid residues generating Leu-Enk Arg6, but it is less active on other neuropeptides containing dibasic stretches. It is optimally active at neutral pH, sensitive to EDTA and slightly affected by the serine protease inhibitors DFP and PMSF. A similar membrane-bound enzyme present in the same tissue was solubilized with 0.5% Triton X-100 and isolated with the same purification procedure. This latter enzyme showed almost identical properties with the soluble peptidase, except for a slightly higher molecular weight. PMID- 1913173 TI - Antinociceptive synergism between supraspinal and spinal sites after subcutaneous morphine evidenced by CNS morphine content. AB - Morphine antinociception after various administration routes was estimated by the tail-flick method in rats. The antinociceptive ED50 (AD50) values for i.c.v., i.t., i.c.v. + i.t. (4:1 dose ratio) and s.c. were 6.9 micrograms, 0.49 + 0.12 micrograms and 2.7 mg/kg, respectively. Isobolographic analysis of AD50 (except s.c.) suggested that concurrent administration of i.c.v. and i.t. morphine interacted multiplicatively to produce antinociception. Morphine content in the CNS after administration of AD50 morphine for each route was estimated. Isobolographic analysis of morphine content revealed that supraspinal and spinal morphine interacted multiplicatively to produce antinociception after i.c.v. + i.t. and s.c. administration. Comparison of the dose-response curves (i.c.v. alone, i.t. alone, various i.c.v. + fixed i.t., fixed i.c.v. + various i.t.) suggested that supraspinal and spinal morphine can potentiate the antinociception induced by the other site, and that they have almost equal importance in the antinociceptive synergism. These results provide direct evidence for the synergism between supraspinal and spinal morphine to play an important role in the antinociception of systemically administered morphine. PMID- 1913174 TI - Interaction between pressor and depressor areas in cat ventrolateral medulla. AB - The purpose of the present study was to investigate whether stimulation of the caudal depressor area (CA) in the medulla lowered blood pressure (BP) by enhancing GABA release at the intermediate pressor area (IA) of the medulla. Application of the excitotoxin kainic acid (KA; 40 mM solution) to the caudal area lowered BP as has been previously described (Gatti, et al., Brain Research, 330 (1985) 21-29). Subsequent IA application of the GABA receptor antagonists picrotoxin (100 micrograms/side) or bicuculline (10 micrograms/side) consistently reversed this hypotensive effect. Picrotoxin raised BP by 92 +/- 10 mmHg (n = 5) after KA while by itself, picrotoxin only increased BP by 23 +/- 7.0 mmHg (n = 3) when applied to the IA. This effect was significantly greater following KA application to the caudal area (P less than 0.05). Likewise, bicuculline raised BP by 74 +/- 8.7 mmHg (n = 7) following KA while by itself, bicuculline only increased BP by 24 +/- 8.2 mmHg when applied to the IA (n = 4). This also was significantly different. This potentiation was not seen with the glycine receptor antagonist, strychnine. These data indicate that there is a GABAergic input from the caudal to the intermediate ventral surface areas of the cat which is involved in the central control of BP. PMID- 1913175 TI - High-affinity choline uptake carrier in Alzheimer's disease: implications for the cholinergic hypothesis of dementia. AB - We examined the density and the state of affinity of [3H]hemicholinium-3 ([3H]HC 3) binding sites, a marker of the presynaptic high-affinity choline uptake (HACU) carrier, in 4 representative regions of 13 postmortem Alzheimer's disease (AD) brains, as well as in 12 matched control brains. Significant reductions in the densities of [3H]HC-3 binding sites were found both in frontal cortex (-44.7%) and hippocampus (-36.5%) of AD brains in comparison to controls. On the other hand the densities of [3H]HC-3 binding sites in AD brains in caudate-putamen and cerebellar cortex showed no significant differences when compared to controls. No significant change in the state of affinity of these sites could be observed in the saturation assays carried out in hippocampus and frontal cortex. Our findings concur with the reported data by using other presynaptic cholinergic markers in AD and confirm that some degree of cholinergic degeneration, highly specific for the basal forebrain neurons, occurs in AD. However, these results, obtained in a group of AD brains belonging to severely demented patients, do not show a dramatic loss of the HACU in many AD brains. Although this fact could be due to the existence of a compensatory mechanism, our results probably suggest that dementia in AD cannot be explained only by the loss of neocortical cholinergic presynaptic terminals arising from the basal forebrain and also may clarify as to why the acetylcholine precursors or the muscarinic agonists are not effective in AD dementia. PMID- 1913176 TI - Effects of short and long-lasting diabetes mellitus on mouse brain monoamines. AB - Concentrations of monoamines and their metabolites were investigated in various brain regions of 3, 50, and 100 days diabetic mice. An increase in the content of norepinephrine was observed in the pons-medulla and striatum in short-term (3 days) diabetic mice, and could be sustained for 100 days and 50 days, respectively. In the hypothalamus and cortex, the increase of norepinephrine was observed in both 50 and 100 day diabetic mice, but that of cerebellum was only observed in the 100 day diabetic mice. The concentration of dopamine was increased in the striatum both in short-term and long-term (50 and 100 days) diabetic mice, that of pons-medulla and cortex was increased in the long-term diabetic mice. Concentrations of the acidic metabolites of dopamine, dihydroxyphenylacetic acid and homovanillic acid were decreased in the hypothalamus, hippocampus and striatum, while increased in the pons-medulla and cortex. 5-Hydroxytryptamine concentration was increased in the hypothalamus, hippocampus, pons-medulla and cortex progressively from short-term to long-term diabetic mice. However, the concentration of its acidic metabolite, 5 hydroxyindoleacetic acid, was decreased in the hypothalamus, hippocampus, striatum, pons-medulla and cortex. These data suggest that diabetes is associated with a significant disturbance of brain monoamine metabolism. This disturbance was not generalized but related to some specific areas of the brain and some of these alterations were progressive from short term to long term diabetes. PMID- 1913177 TI - Pharmacological consequences of cholinergic plus serotonergic manipulations. AB - The present study investigated pharmacological consequences of combined cholinergic and serotonergic blockade. Raphe medianus (RM) lesions (5,7-DHT) had no effect on spatial learning, but augmented scopolamine 0.8 mg/kg induced learning deficit. Pilocarpine (4 mg/kg) could reverse scopolamine (0.8 mg/kg), but not scopolamine (0.8 mg/kg) + RM lesion induced spatial learning impairment. However, a higher dose of pilocarpine could restore spatial learning deficit induced by scopolamine (0.8 mg/kg) and RM lesions. These findings support the important role of cholinergic-serotonergic interaction in the regulation of spatial learning and suggests that the combined cholinergic-serotonergic deficit in patient's with Alzheimer's disease may have an impact on therapeutic approaches which seek to normalize AD related cognitive impairments. PMID- 1913178 TI - Progression of regeneration after nerve infarction. AB - We performed morphologic studies on the progression of regeneration in cat hind limb nerves after acute ischemic injury. None of the damaged nerve trunks showed a major increase in endoneurial connective tissue. Despite this fact, regeneration of nerve with transfascicular infarct was far from complete even 16 months after injury as manifested by a striking increase in the small myelinated fibers (MF) number and decrease in large MF number. Restoration of infarcted nerves was less complete than that previously reported after a nerve crush. Changes in the necrotic nerve segment and difficulty in making target contact with muscle and other tissues damaged by ischemia may be limiting factors in the regeneration of infarcted nerves. PMID- 1913179 TI - Geniculo-hypothalamic tract lesions block chlordiazepoxide-induced phase advances in Syrian hamsters. AB - Administration of the benzodiazepine triazolam at the appropriate time in the circadian cycle has been shown to induce phase shifts in hamster circadian rhythms. These phase shifts can be blocked by geniculo-hypothalamic tract (GHT) ablation or by restraint of activity. The present study examined the effects of the benzodiazepine chlordiazepoxide on running-wheel activity rhythms of hamsters. The phase-advancing effect of intraperitoneal injections of chlordiazepoxide administered at circadian time 6 (CT 6) was dose-dependent. Average shifts ranged from 6 min at a dose of 0.05 mg/kg to 135 min at a dose of 200 mg/kg. Four of twenty hamsters did not show a phase shift to any dose tested. Phase advance shifts to chlordiazepoxide (CT 6; 100 mg/kg) were blocked by GHT lesions. Chlordiazepoxide injections at doses which induced phase shifts were often followed by sedation. These results indicate that chlordiazepoxide is similar to triazolam, in that its ability to induce phase shifts at circadian time 6 is blocked by GHT lesions. PMID- 1913180 TI - The effects of GABA and benzodiazepines on neurones in the suprachiasmatic nucleus (SCN) of Syrian hamsters. AB - Administration of benzodiazepines at appropriate times in the circadian cycle induce phase-shifts in circadian locomotor activity. The possibility that benzodiazepine-induced shifts are mediated at the level of the suprachiasmatic nuclei (SCN), identified as the circadian pacemaker in mammals, was examined electrophysiologically. Extracellular recordings were made from Syrian hamster (Mesocricetus auratus) hypothalamic SCN neurones in vitro to assess (1) the effects of gamma-aminobutyric acid (GABA) on SCN neuronal activity and (2) the effects of benzodiazepines (chlordiazepoxide and flurazepam) on GABA-evoked responses. Of 93 SCN cells tested, 86 were suppressed by iontophoresed GABA (20 mM) in a current(dose)-dependent manner, while 6 were unaffected; suppression was found during both the projected light and dark phases of the circadian cycle. Application of bicuculline methiodide alone elevated mean discharge activity, while GABA-evoked suppressions were blocked by bicuculline (n = 9/11 cells). Iontophoresis of chlordiazepoxide or flurazepam (20 mM; 1-10 nA) alone produced a current(dose)-dependent prolonged suppression of cell firing which was antagonised by bicuculline. These results indicate that benzodiazepine/GABA evoked responses are at least partially mediated by GABAA receptors within the SCN and suggest that SCN may be a possible locus for the action of benzodiazepines in their induction of phase-shifts in circadian function. PMID- 1913181 TI - Vagal and somatic representation by the climbing fiber system in lobule V of the cat cerebellum. AB - The organization of the climbing fiber representation of the vagal afferents and the body surface in the vermal and intermediate zones of lobule V was examined in cats anesthetized with alpha-chloralose. Extracellular single-unit recordings were made from 428 Purkinje cells. Electrical stimulation of the vagus nerve elicited climbing fiber responses in 40% of the cells, most of which had convergent somatic input. Activation of A delta vagal afferent fibers accounted for 65% of the responses, whereas the A beta fibers involved 27% and the C fibers included 8% of the responses. The responses driven by vagal nerve stimulation were encountered throughout the lobule, although a significantly increased representation of the vagus was identified for 3 longitudinal 0.5 mm wide sectors (two in the vermis and one in the intermediate region). In the vermis, the fine grain organization consisted of a mixture of representations of the various parts of the body surface with and without convergent vagal input, although there was little convergence in the medial vermis where many of the responses were elicited by only vagal nerve stimulation. In the intermediate cortex, most of the vagal climbing fiber representation was convergent with forelimb input. These results suggest that vagal input into the cerebellum could have important modulatory effects on the cerebellar somatosensory input. PMID- 1913183 TI - On the relation of PAG neurons to laryngeal and respiratory muscles during vocalization in the monkey. AB - Despite evidence from previous unit recording, microstimulation, lesioning and anatomical studies, the functions of the midbrain periaqueductal gray (PAG) remain unclear. We attempted to clarify the function of the PAG by recording activity of PAG units along with laryngeal and respiratory electromyograms (EMG) during vocalization in awake monkeys. PAG units were classified with respect to vocalization on the basis of their discharge patterns as 'early burst', 'late burst', 'tonic-increase' and 'tonic-off', with the vast majority being of the early- and late-burst type. Early-burst cells were correlated most frequently with inspiratory muscles of the respiratory system and laryngeal abductor muscles. Late-burst cells were most clearly correlated with laryngeal adductor and expiratory respiratory muscles. Data from spike-triggered averaging and parametric correlations indicate that most cells are related to single muscles, but a significant number were related to functionally related groups of two or more muscles. The results suggest that the PAG determines qualitative aspects of vocalization by the multisynaptic action its cells have on laryngeal and respiratory motoneurons. PMID- 1913182 TI - Immortalization of embryonic mesencephalic dopaminergic neurons by somatic cell fusion. AB - To facilitate the study of trophic interactions between mesencephalic dopaminergic neurons and their target cells, clonal hybrid cell lines have been developed from rostral mesencephalic tegmentum (RMT) of the 14-day-old embryonic mouse employing somatic cell fusion techniques. Among the hybrid cell lines obtained, one contains a high level of dopamine (DA), another predominantly 3,4 dihydroxyphenylalanine (DOPA), and a third no detectable catecholamines. The hybrid nature of the cell lines is supported by karyotype analysis and by the expression of adhesion molecules as assessed by aggregation in rotation-mediated cell culture. The DA cell line shows neuronal properties including catecholamine specific histofluorescence, neurite formation with immunoreactivity to neurofilament proteins, and large voltage-sensitive sodium currents with the generation of action potentials. In contrast to the pheochromocytoma cell line (PC12), the dopamine content of the DA hybrid cell line is depleted by low concentrations of N-methyl-4-phenylpyridinium ion (MPP+), the active metabolite of the neurotoxin N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). PMID- 1913184 TI - Suppressive effects of L-5-hydroxytryptophan in a feline model of photosensitive epilepsy. AB - We recently demonstrated that long-lasting photosensitivity is acquired as a result of kindling of the lateral geniculate nucleus (LGN), and that the LGN kindled cat pretreated with D, L-allylglycine represents a useful model of epilepsy for drug studies. The present experiments studied anticonvulsant effects of a serotonin precursor, L-5-hydroxytryptophan (5-HTP), on photosensitivity in the LGN-kindled cat under D,L-allylglycine and on LGN-kindled seizures. 5-HTP suppressed both myoclonic responses and paroxysmal EEG discharges induced by photic stimulation in a dose-related manner. Photically-induced seizures were completely blocked 1.5-2 h after injection of 20 mg/kg 5-HTP. 5-HTP was also effective in reducing the afterdischarge duration and behavioral seizure stage in LGN-kindled seizures; following 40 mg/kg administration, no electroclinical seizures were elicited in the LGN-kindled cats. Serotonergic mechanisms may play an important role in epileptic photosensitivity; the 5-HTP suppressive effect on photosensitivity is at least partly due to reduced neuronal activity at the level of the LGN via serotonergic inhibition. PMID- 1913185 TI - The effect of subtype-selective muscarinic receptor antagonists on the cholinergic current in motoneurons of the lobster cardiac ganglion. AB - Muscarinic agonists evoke a voltage-dependent inward current in motoneurons of the lobster cardiac ganglion. In this study, a number of drugs, known to show muscarinic receptor subtype selectivity in mammals, were used to determine the pharmacological profile of the muscarinic receptor on lobster motoneurons. The neurons were held under voltage-clamp, and various concentrations of the antagonists were applied in the presence of 1 mM methacholine. From competition curves plotting agonist-induced current against antagonist concentration, the inhibitor affinity constant and the slope factor were determined. The rank order of potencies of antagonists having an effect was: atropine greater than pirenzepine greater than 4-DAMP greater than methoctramine greater than HHSiD = (R)-HHD greater than (S)-HHD. Neither AF-DX 116 nor gallamine were effective at concentrations as high as 10 mM. The M1-selective agonist McN-A-343 had no effect. Although this crustacean muscarinic receptor resembles the mammalian M1 muscarinic receptor because of its relatively high affinity for pirenzepine, the rank order of other subtype-specific antagonists does not otherwise resemble that of any of the pharmacologically defined muscarinic receptors in mammals. It may be preferable, therefore, to use a term such as 'pirenzepine-sensitive' muscarinic receptor rather than M1 or 'M1-like' for invertebrate muscarinic receptors with pharmacological characteristics like those reported here. PMID- 1913186 TI - Focal ischemia in rats causes time-dependent expression of c-fos protein immunoreactivity in widespread regions of ipsilateral cortex. AB - c-Fos protein expression was examined in brain by immunohistochemistry following permanent middle cerebral artery (MCA) occlusion above the rhinal fissure and ipsilateral common carotid artery (CCA) occlusion in Long-Evans rats. In sham operated animals, c-fos protein-like immunoreactivity (CFPLI) was confined to neuronal nuclei of the hypothalamus and was not present in other regions including cerebral cortex. In the core territory of the MCA, CFPLI was not detected when examined at 15 and 30 min, 1, 4 and 8 h and 1, 2, 4 and 7 days after occlusion. Focal ischemia induced two temporal and spatial patterns of CFPLI. At 1 h, c-fos protein was expressed in the nuclei of many neurons in layers II-V of the ipsilateral cortex both immediately adjacent to and remote from the ischemic territory. Within regions outside the MCA territory (e.g. cingulate gyrus and piriform cortices), CFPLI in these neurons peaked at 2-4 h and was undetectable after 2 days. Neurons in the zone immediately surrounding the ischemic core within MCA territory also expressed CFPLI, but in contrast, continued to express c-fos up to 4 days after ischemia. Immunoreactivity surrounding the ischemic core was found in neuronal nuclei predominantly, although from 1 to 4 days, CFPLI was found in perikarya and dendrites as well. MK 801 (3 mg/kg, i.p., 30 min prior to occlusion) completely blocked the early c-fos protein induction in all regions but expression within neurons surrounding the ischemic core was present 1 day after a single injection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1913187 TI - Neuropeptide Y and food intake in fasted rats: effect of naloxone and site of action. AB - Central administration of neuropeptide Y (NPY) induces food intake in freely feeding animals and this effect is mediated by hypothalamic sites. Little is known, however, about the effect of NPY on food intake and site of action in food deprived animals. To examine this further, 24-h fasted rats received injections of saline or NPY into the lateral cerebral ventricle (10 micrograms/10 microliters; n = 8) or into the lateral (LH) or ventromedial hypothalamus (VMH) (1 microgram/0.5 microliters; n = 44). In addition, intracerebroventricular (i.c.v.) injections of NPY were carried out with or without i.c.v. naloxone (25 micrograms), a specific opioid receptor antagonist. During the first 40 min food intake was not different with or without NPY. After 60 and 120 min, food intake was 5.9 +/- 0.4 g and 8.3 +/- 0.6 g with i.c.v. saline which was significantly augmented by i.c.v. NPY to 8.7 +/- 0.9 g and 14.4 +/- 1.5 g, respectively (P less than 0.05). This increase in food consumption was due to a prolongation of feeding time. The opioid receptor antagonist naloxone significantly augmented latency to feed, both in the absence and presence of NPY (8.0 vs 1.7 min or 14.7 vs 2.8 min, respectively) and abolished the NPY-induced increase in food intake. Following intrahypothalamic injection of NPY, an increase in food intake (greater than 20%) was observed in 50% of the histologically identified LH and VMH sites, but only in 15% of the injection sites outside the LH/VMH.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1913188 TI - Egg laying hormone inhibits a neuron (C-PR) involved in multiple manifestations of food-induced arousal in Aplysia. AB - Egg laying behavior is known to suppress feeding in Aplysia, but both behaviors have common responses involving head movements and posture. Egg laying hormone (ELH) applied in vitro to the isolated nervous system of Aplysia reduces the spontaneous and the evoked activity of the C-PR, a neuron implicated in postural responses during feeding. The inhibitory effect of ELH on the C-PR appears to be mediated by interneurons primarily located in the pedal/pleural ganglia, which contain all the known direct follower cells of the C-PR. Our results do not support the idea that postural responses during feeding and egg laying are mediated by the activation of a common arousal element, the C-PR. In fact, the C PR seems to be a specific element for the food-arousal state, and the inhibition of the C-PR by ELH may contribute to the suppression of appetitive feeding responses during egg laying. PMID- 1913189 TI - The ventrolateral medulla of the cat mediates vestibulosympathetic reflexes. AB - Extracellular recordings were made from 94 neurons located in the ventrolateral medulla (VLM) whose firing rate was affected by vestibular nerve (VN) stimulation; 50 of these units were in the subretrofacial (SRF) nucleus, which contains cells that make direct excitatory connections with sympathetic preganglionic neurons. The sample included 12 SRF cells which were antidromically driven from the upper thoracic spinal cord and had conduction velocities of 10 m/s or less; the effect of VN stimulation on all but one of these units was inhibition. The onset latency of the response to VN stimulation was long [20.3 +/ 3.7 (S.E.M.) ms, n = 9, for the antidromically activated neurons and 12.1 +/- 1.2 ms, n = 73, for the others], suggesting that the effects were predominantly polysynaptic. In addition, most of the spontaneously active units tested (33/36) received convergent inputs from the carotid sinus nerve (CSN), as would be expected for neurons which influence sympathetic outflow. Vestibular-elicited inhibition of SRF neurons with projections to the intermediolateral cell column could account for late, long duration inhibition of sympathetic discharges produced by labyrinth stimulation. PMID- 1913190 TI - Potentiation of angiotensin II-induced drinking by glucocorticoids is a specific glucocorticoid type II receptor (GR)-mediated event. AB - Earlier studies showed that pretreatment (3 and 6 h) of rats with the glucocorticoid hormone, dexamethasone, potentiated the drinking response to either central or peripheral administration of angiotensin II (AII). In the present study the specificity and mechanisms of this potentiation were examined. Intraperitoneal (i.p.) injection of rats with the pure glucocorticoid agonist, RU 28362 (0.4-1.6 mg/kg; 3-24 h), resulted in a time- and dose-dependent potentiation of the drinking responses to either peripherally (100 micrograms/kg, s.c.) or centrally (10 ng) injected AII, similar to the effects of dexamethasone. Drinking induced by central injection of carbachol (200 ng) was unaltered by pretreatment with RU 28362, suggesting that potentiation by this compound was specific for AII. The potentiation of AII-induced drinking by either dexamethasone or RU 28362 was completely abolished by pretreatment with the glucocorticoid Type II receptor (GR) antagonist, RU 38486 (2 mg/kg, i.p.), but not by the mineralocorticoid Type I receptor (MR) blocker, mespirenone (2 mg/kg, i.p.). Taken together, these results indicate that the glucocorticoid-induced potentiation of AII-induced drinking is mediated via GR. Associated with the fact that glucocorticoids potentiate AII-induced drinking is the observation that these steroids also potentiate AII-induced urine output. This enhancement of urine output may explain in part the potentiation in drinking behavior. Possible mechanisms are discussed. PMID- 1913191 TI - DNQX blockade of amphetamine behavioral sensitization. AB - The role of the N-methyl-D-aspartate (NMDA) and non-NMDA excitatory amino acid (EAA) receptors in the mechanism of behavioral sensitization to amphetamine induced sterotypy was investigated in mice. The results confirm previous observations that NMDA antagonists can block the induction of the phenomenon but not the expression; in contrast, DNQX, a non-NMDA receptor antagonist, can block both the induction and the expression of the sensitization. The differential effects of the two classes of antagonists suggest that the induction and the expression are the result of different mechanisms, both of which involve the EAA system. The DNQX results differ from those of haloperidol, which can also block both the induction and expression, because haloperidol can completely block the amphetamine-induced responses in naive and in sensitized animals; whereas DNQX is without effect on the amphetamine activity in naive animals and, in the sensitized animal, can block only that portion of the response that is derived from the sensitization phenomenon. The effects of the EAA antagonists support the hypothesis that the enhanced responsiveness in the sensitized animals is derived from the activation of EAA receptors, which, in turn, increases the release of dopamine in the striatum. Finally, the involvement of the non-NMDA receptors in the expression of the behavioral sensitization further substantiates the postulate that the amphetamine-induced sensitization is a behavioral manifestation of long-term potentiation (LTP). PMID- 1913192 TI - Neuronal localization of cannabinoid receptors and second messengers in mutant mouse cerebellum. AB - Four lines of mutant mice were used to investigate (1) the neuronal localization of cannabinoid receptors in the cerebellar molecular layer and (2) the anatomical association of these receptors with elements of the two second messenger systems in the brain. Two of the mutant lines--Purkinje cell degeneration and nervous- are selectively deficient in Purkinje cells; the other two--weaver and reeler- are deficient in granule cells. In the heterozygous mice, [3H]CP 55,940 binding to cannabinoid receptors was discretely and densely localized to the molecular layer, as was [3H]forskolin binding to adenylate cyclase and [3H]phorbol 12,13 dibutyrate binding to protein kinase C, a component of the phosphoinositide cycle. [3H]CP 55,940 and [3H]forskolin binding was selectively reduced in weaver and reeler homozygous mice but unchanged in Purkinje cell deficient and nervous homozygotes. No decreases in [3H]phorbol 12,13-dibutyrate binding were found in any of the homozygous mutants relative to the heterozygous littermates. The results suggest that cannabinoid receptors and adenylate cyclase are localized to granule cell axons in the molecular layer, whereas protein kinase C is equally distributed in parallel fibers and Purkinje cell dendrites. PMID- 1913194 TI - REM sleep deprivation reduces auditory evoked inhibition of dorsolateral pontine neurons. AB - In many dorsolateral pontine neurons, auditory stimulation produces an initial excitation followed by a sustained inhibition. We now report that rapid eye movement (REM) sleep deprivation, for periods of from 22-48 h, reduced this auditory evoked inhibition of unit discharge. Inhibition returned to baseline levels after recovery REM sleep. Prior work indicates that the auditory evoked inhibition seen in noradrenergic cells in this region is partially mediated by norepinephrine. We hypothesize that the reduction in inhibition that we see is a consequence of either downregulation/desensitization of norepinephrine receptors or reduced norepinephrine release resulting from REM sleep deprivation. PMID- 1913193 TI - Evidence for invasion of regenerated ventral root afferents into the spinal cord of the rat subjected to sciatic neurectomy during the neonatal period. AB - Sectioning the sciatic nerve of experimental animals at the neonatal stage triggers growth of afferent fibers in the ventral root. The present study examined the possibility that the regenerating fiber terminals grow into the spinal cord. The sciatic nerve on one side was cut in neonatal rats. After the rats were fully grown, either an electrophysiological or a histochemical study was performed. The results of electrophysiological experiments showed that stimulation of certain loci in the L5 spinal cord evoked antidromic potentials in the L5 ventral root with a long latency. Various evidence suggests that the long latency potentials are due to activation of C fibers. These C-fiber potentials were on average bigger and were elicited from more numerous loci on the side ipsilateral to the sciatic nerve lesion than on the contralateral side. Furthermore, stimulation of the spinal cord of unoperated normal rats rarely evoked such potentials. For the histochemical study, horseradish peroxidase (HRP) was injected into the L5 spinal cord after cutting the L4-L6 dorsal roots. A lot more cells in the L5 dorsal root ganglion (DRG) on the side ipsilateral to the sciatic nerve lesion were labeled with HRP transported retrogradely through the L5 ventral root than on the contralateral side. Control experiments showed that few DRG cells are labeled with HRP in normal unoperated rats. The combined results of the electrophysiological and histochemical studies suggest invasion of ventral root afferents into the spinal cord, given enough postoperative time. It is not known whether or not these terminals make functional synaptic contacts in the spinal cord. PMID- 1913195 TI - The effects of dizocilpine (MK-801), phencyclidine, and nimodipine on infarct size 48 h after middle cerebral artery occlusion in the rat. AB - The effects of the calcium channel blocker nimodipine and the non-competitive NMDA-antagonists MK-801 and phencyclidine (PCP) on infarct size 48 h after occlusion of the middle cerebral artery (MCA-O) were evaluated in the rat. Nimodipine was given at a dose of 0.3 mg/kg s.c. 30 min prior and 8, 16, and 24 h after MCA-O. MK-801 (1 mg/kg i.p. or 10 mg/kg i.p.) or PCP (0.3, 1.0, 3.0, 10, or 30 mg/kg i.p.) were administered 30 min prior to ischemia. In additional experiments 30 mg/kg PCP was given 1, 3, or 5 h post ischemia. Nimodipine and 1 mg/kg MK-801 reduced cortical infarct volumes significantly by 50% and 55%, respectively, while cortical infarct size fell by 32% and total infarct volume was not altered significantly after administration of 10 mg/kg MK-801. Pretreatment with 10 or 30 mg/kg PCP reduced cortical infarction by 47-53% and total infarct volumes by 39-42%. Posttreatment with PCP was effective if started at 1 or 3 h post ischemia. PMID- 1913196 TI - Naloxone enhances the release of acetylcholine from cholinergic interneurons of the striatum if the dopaminergic input is impaired. AB - Naloxone significantly enhanced the release of radioactive acetylcholine ([3H]ACh) from rat striatal slices loaded with [3H]choline either when the nigrostriatal pathway had been destroyed by 6-hydroxydopamine or when the D2 dopamine receptors had been inhibited by sulpiride. This in vitro study supplies the first neurochemical evidence, that, in addition to D2-receptor-mediated dopaminergic tonic control, there is opiate-receptor mediated presynaptic modulation of striatal ACh release, possibly by endogenous enkephalin released from local neurons. Such modulation occurs under conditions in which the dopaminergic input is impaired. PMID- 1913197 TI - Loss of dendritic synapses in the medial amygdala associated with kindling. AB - Kindling stimulation was given in the basolateral amygdala (BLA), the septal area or the corpus callosum in the right hemisphere of adult rats. The density of dendritic synapses was electron microscopically studied in the medial amygdaloid nucleus (MAN) ipsi- and contralateral to the stimulation side. The number of dendritic synapses was markedly decreased in both sides of the MAN of 3 groups of kindled rats. Such reduction occurred in both dendritic shaft and spine synapses. The most remarkable decrease was obtained in the BLA kindling. These results suggest that a decrease of synapses may provide a morphological basis for kindling. PMID- 1913198 TI - [Mechanisms of the effect of allopurinol on the metabolism of adenine nucleotides]. AB - The effect of repeated administration of allopurinol (50 mg.kg-1 48, 24, and 4 hours before analysis) on the activity of enzymes of degradation and resynthesis of adenine nucleotides was studied. The activity of xanthine dehydrogenase and xanthine oxidase was inhibited in the heart, liver and kidney and the activity of membrane-bound 5'-nucleotidase was particularly elevated in the heart and brain, suggesting that membrane transport processes may be affected. The increase in the activity of hypoxanthine guanine phosphoribosyl transferase in the liver is indicative of a potential mechanism of positive action of allopurinol upon restoring the purine nucleotide store. The authors present their hypothesis on the mechanism of allopurinol action upon the metabolism of adenine nucleotides. The suggested mechanisms might become operative in protecting tissues against ischemia and reperfusion induced damage. PMID- 1913200 TI - [Hypertensive disease in the elderly and its treatment]. AB - After presenting the epidemiologic and pathophysiologic pattern, the paper focuses on the evaluation of elderly hypertensives, on nonpharmacological and particularly on pharmacological treatment. Further, possibilities of individualized treatment, resistance to treatment, complications of hypertensive disease in elderly subjects, as well as beneficial effects of management are described. PMID- 1913199 TI - [The effect of tetracycline and vitamin E on energy metabolism in cardiac mitochondria of old rabbits pretreated with isoproterenol]. AB - The possibility of eliminating adverse effects of tetracycline and isoproterenol pretreatment on energy generation of myocardial mitochondria by vitamin E administration was investigated in old rabbits. Vitamin E administered in doses of 1.5 mg per kg body weight over 6 days was found to improve energy metabolism in old rabbits whose metabolism had been deranged by isoproterenol pretreatment in the dose of 1.5 mg per kg body weight. Subsequent administration of vitamin E to rabbits pretreated with isoproterenol and tetracycline in doses of 15 mg per kg body weight daily over 6 days also resulted in improvement of energy metabolism parameters studied. Under the given conditions vitamin E was found to exert a protective effect on oxidative phosphorylation of the myocardium damaged by isoproterenol and tetracycline. PMID- 1913202 TI - [The effect of glutaraldehyde preparations on the properties of biological heart valve prostheses]. AB - Changes in hydrodynamic properties of biological valve prostheses (37 aortic allotransplants, 40 pericardial allotransplants) induced by glutaraldehyde treatment were studied in vitro. With the exception of sufficiency, the majority of hydrodynamic characteristics exhibited significant deterioration after glutaraldehyde treatment when compared to the data in untreated valves. The value of the dynamic test of valve prostheses is pointed out. PMID- 1913201 TI - [Comparison of changes in uterine reactivity to endogenous substances in rabbits and the effect of in vivo and in vitro administration of estradiol and testosterone]. AB - Changes in uterus reactivity were studied in the rabbit after single and repeated administration of estradiol in the dose of 5 mg.kg-1 and of testosterone in the dose of 10 mg.kg-1. On applying the hormones in vitro, 1.8 x 10(-5) mol of estradiol and 5.8 x 10(-5) mol of testosterone was used. The method of isometric contraction served to study the cumulative curves of the uterus to histamine (HIST), serotonin (SEROT), and angiotension (ANGIO). Both after single and repeated administration of the hormones, the contractile response of the uterus to the substances studied was mostly increased. After hormonal pretreatment in vitro, the contractile responses of the uterus were predominantly reduced, and this diminished response was more pronounced after testosterone. Repeated hormonal pretreatment resulted in hypertrophy of the longitudinal and circular musculature, which was more marked after testosterone application. The results indicate that testosterone, similarly as estradiol, can affect the contractility of the uterus both at receptor and nonreceptor levels, as well as by its effect on the morphology of the uterus. PMID- 1913203 TI - [The importance of albuminuria in the detection of diabetic nephropathy and its relation to the development of retinopathy and autonomic neuropathy in type I diabetes]. AB - A series of 72 type I diabetics was grouped according to the mean value of 24-h albuminuria (AU) determined from three 24-h urine collections: group A (n = 49, normoalbuminuria, AU less than or equal to 26 mg/24 h), group B (n = 16, microalbuminuria, AU less than or equal to 26 mg/24 h), group C (n = 7, clinically significant proteinuria, AU greater than 260 mg/24 h). Glycosylated hemoglobin (GHb) was examined five times in three-month intervals. Systolic and diastolic blood pressure (BPs and BPD) were determined from four values taken in the course of one year. Glomerular filtration (GF) was established a single examination of 24-h creatinine clearance. Fluorescent angiography was used to examine the fundus of the eye. The function of the cardiovascular autonomic nervous system was assessed on the basis of three tests: variation of heart rate during deep respiration, response of heart rate to upright position, Valsalva's maneuver. Group C had the longest duration of diabetes, the highest GHb, the lowest GF, and the highest BPS and BPD values. The number of diabetics with different findings on the fundus of the eye (normal finding/simple retinopathy/preproliferative and proliferative retinopathy) was as follows: group A--15/31/3, group B--9/6/1, group C--0/3/4. Group C exhibited the most pronounced derangement of the cardiovascular autonomic nervous system, whose extent depended on the length of diabetes duration and on the quality of metabolic compensation. Between the groups A and B no significant differences were found in any of the parameters studied.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1913204 TI - Principles of magnetic resonance imaging: applications in cardiovascular system. PMID- 1913205 TI - [Recent trends in the treatment of lower leg fractures]. AB - Indications of appropriate treatment of tibial shaft fractures are one of the priority problems present-day traumatology has to address. In choosing the optimal mode of treatment of tibial shaft fractures not only the configuration of the fracture but also injury of soft tissues has been assigned increasing importance. At the Department of Traumatology of the Postgraduate Institute of Medicine in Bratislava, 962 tibial shaft fractures were treated over the period of 12 years from 1977-1988. Conservative treatment was applied in 600 fractures and 362 fractures were treated surgically. The therapeutic results obtained by using the newly introduced methods of treating tibial shaft fractures, i.e. functional plating and osteosynthesis by flexible Ender nailing, were analyzed in a retrospective and prospective study. The results of these approaches were compared with those achieved by classical methods of the AO school, rigid intramedullary nailing and external fixation. The favorable outcome of union and the good functional effect obtained in the studied and compared series of patients indicate that conservative functional treatment is the method of choice in tibial shaft fractures. Of the surgical therapeutic methods, flexible as well as stable intramedullary osteosynthesis by Ender nailing proved to be both the most sparing and the most physiological approach. The paper proposes an indication scheme of tibial shaft fracture treatment designed for clinical use considering the categorization of fractures according to up-to-date classification. For each type of tibial shaft fracture and soft tissue injury the optimal mode of treatment is suggested. Besides the main indication, possibilities of alternative treatment are also being pointed out. PMID- 1913206 TI - [Reference values of dipolar electrocardiotopography of the QRS complex]. AB - Reference values of dipolar electrocardiotopogram of ventricular depolarization are presented. The data for establishing reference values in the McFee-Parungao lead system were obtained by manual processing of 145 records of healthy subjects (64 women, 81 men) in the age range of 11-72 years, and for the Frank lead system by automatic processing of 123 records of healthy subjects (54 women, 69 men) aged from 9 to 72 years. The obtained values of the X, Y, Z coordinates of the end points of QRS instantaneous vectors recorded at 10 ms intervals were processed by means of a biomathematical model in the form of activation areas on the spherical image surface. Electrocardiotopograms were represented in the form of discrete spherical image surface in the shape of a rectangle (11 lines, 24 columns). For each point of this matrix the value of relative frequency (probability) of its occurrence in activated state in the healthy population is given. PMID- 1913207 TI - [Serum lipids in obese persons in a selected population in the Slovak Republic]. AB - Serum lipid levels were determined in 287 obese subjects and the findings were compared with the mean values recorded in a representative series of the population of the Slovak Republic (n = 3433). Comparison of serum lipid values in age-matched groups from the two series showed the following results: significant increase of triacylglycerols in obese men aged 15-55 y, in obese women aged 15-35 y; significant increase of total cholesterol in obese men aged 26-55 y, in obese women aged 26-35 y; significant reduction of HDL cholesterol in obese men after 25 years of age and in obese women after 35 years of age. Obesity was found to increase significantly serum lipid levels, particularly in men with predominant central-abdominal type of obesity. PMID- 1913208 TI - Compositional variations in DNA sequences. AB - Biologically occurring nucleotide sequences differ from randomly generated ones. Here we describe general patterns found in prokaryotic and in eukaryotic DNA. In the accompanying paper (Nussinov, 1991) we also describe DNA signals recognized by their corresponding protein factors. In particular, we focus on modes of searches for such patterns and signals and on the potential properties such sequences may possess. PMID- 1913209 TI - Signals in DNA sequences and their potential properties. AB - DNA and RNA molecules contain signals which are recognized by regulatory proteins or enzymes either directly, through their nucleotide sequences or indirectly, through induced structural changes on their neighboring sequences. To date, most signal searches have been focused on specific recurrences of nucleotide sequences. Much less attention has been directed towards the structure, flexibility and hydrogen-bonding patterns that recognition elements may possess. Here we review the various methods involved in such searches. In particular, however, we also address the searches for potential properties. In this regard it is of interest to inspect the asymmetry in the distributions of complementary oligomers near biological features. Upstream of transcription initiation the frequencies of G-rich oligomers are particularly high (Nussinov, 1987a; 1990). The frequencies of C-rich oligomers are lower. A-tracts are also very frequent in these regions. This may correlate with the recent finding that guanine, but not cytosine, tracts enhance A-tract directed bends (Milton et al., 1990). Presumably A-tracts near G-tracts on the same strand may induce a structural change in the G tracts which may enhance the bend. G-tracts may have the potential for participating in a DNA bend due to their compression of the major groove. Thus, proteins may not always be necessary to induce DNA conformational changes. This example illustrates the importance of studies of the properties of DNA oligomers in regulatory regions, and of algorithms for their detection. PMID- 1913210 TI - Artificial intelligence methods for theory representation and hypothesis formation. AB - This article describes artificial intelligence methods for representing theories in molecular biology, and for improving the predictive power of these theories using experimental data. A program called GENSIM provides a framework for representing theories that includes descriptions of classes of biological objects (genes, enzymes, etc.), and processes that specify potential interactions among these objects (such as enzymatic reactions). GENSIM can employ a theory specified within this framework to predict the outcomes of biological experiments. A program called HYPGENE comes into play when the observed outcome of an experiment does not match the outcome predicted by GENSIM. HYPGENE works backward from the error in GENSIMs prediction to postulate changes to both the theory embodied by GENSIM, and the presumed initial conditions of the experiment. I view HYPGENEs hypothesis generation task as a design problem, and I have adapted AI methods developed for design and planning to this task. These techniques were developed in conjunction with an in-depth study of the discovery of the gene regulation mechanism of attenuation in the E. coli tryptophan operon. Both GENSIM and HYPGENE have been tested on sample problems from the history of attenuation, and produced many of the same solutions as biologists did. PMID- 1913211 TI - Automatic evaluation of protein sequence functional patterns. AB - A procedure that automatically provides an evaluation of the diagnostic ability of a protein sequence functional pattern is described. The procedure relies on the identification of the closest definable set in terms of a (protein sequence) database functional annotation to the set of database instances containing a given pattern. Assuming annotation correctness and completeness in the protein sequence database, the degree of statistical association between these sets provides an appropriate measure of the diagnostic ability of the pattern. An experimental implementation of the procedure, using the NBRF/PIR protein database, has been applied to a diverse collection of published sequence patterns. Results obtained reveal that frequently it is not possible to define (in NBRF/PIR database terminology) the set of database instances containing a given pattern, suggesting either lack of pattern diagnostic ability or protein database annotation incompleteness and/or inconsistencies. PMID- 1913212 TI - A computer program for molecular weight determination of DNA fragments (HOWBIG). AB - The computer program HOWBIG has been developed based on the reciprocal correlation of size to migration distance of DNA in high voltage gradient gel systems (Southern, 1979). For calculation the program automatically chooses three marker bands migrating closest to the calculated band, reducing the error down to approximately 0.5% or less (reciprocal method, local form of calculation). The big advantages of the completely menu-driven program are high accuracy, error detectability, speed and ease of data handling. Management of marker-DNA molecular weights, data and analyses as files included in the menu driven program speeds up every-day lab work. PMID- 1913213 TI - The search for a grammatical theory of gene regulation is formally justified by showing the inadequacy of context-free grammars. AB - No one questions the important practical contributions of computer sciences to molecular biology. It may well be that one day theoretical contributions also will become useful. One example of this type of interdisciplinary research is the attempt to construct a grammatical theory of the regulation of gene expression. In this paper, I demonstrate that context-free grammars are inadequate for the description of regulatory properties coded in the DNA. This result is supported by data available in the literature that show changes in the specificity of the recognition between regulatory proteins and their DNA targets. This result is an important limitation for the use of statistical approaches such as information theory as a source of inspiration for a theory of gene regulation. Additionally, such a demonstration gives formal justification to the search for more elaborate grammatical models in the study of gene regulation. Some basic proposals for such grammatical approach have been presented previously. PMID- 1913214 TI - CAMBIO: software for modelling and simulation of bioprocesses. AB - CAMBIO, a software package devoted to bioprocess modelling, which runs on Apollo computers, is described. This software enables bioengineers to easily and interactively design appropriate mathematical models directly from their perception of the process. CAMBIO provides the user with a set of design symbols and mnemonic icons in order to interactively design a functional diagram. This diagram has to exhibit the most relevant components with their related interactions through biological and physico-chemical reactions. Then, CAMBIO automatically generates the dynamical material balance equations of the process in the form of an algebraic-differential system by taking advantage of the knowledge involved in the functional diagram. The model may be used for control design purpose or completed by kinetics expressions with a view to simulation. CAMBIO offers facilities to generate a simulation model (for coding of kinetics, introducing auxiliary variables, etc.). This model is automatically interfaced with a specialized simulation software which allows an immediate visualization of the process dynamical behaviour under various operational conditions (possibly involving feedback control strategies). An example of an application dealing with yeast fermentation is given. PMID- 1913215 TI - Quantitative densitometry of autoradiograms: digital images representative of optical density. AB - Microcomputer software has been developed to control video acquisition of 1024 x 1024 digital autoradiogram images which represent true optical density (OD). Since video cameras are sensitive to intensity (I), background correction and conversion to OD must be accomplished in software. The software linearizes camera output against an optical step tablet of known ODs and creates a 'look-up table' through which captured images are passed. This procedure allows the accurate and rapid conversion of a large number of images. The user is directed through the calibration and capture procedures; safeguards are included to ensure that the resultant images are correctly calibrated. The algorithms used in these programs accommodate the limited computing power available in microcomputers. The use of a commercially available graphics library will enhance the portability to multiple hardware configurations. This software is a low-cost alternative for the capture of digital images needed for quantitative densitometry. PMID- 1913216 TI - Integrated displays of aligned amino acid sequences and protein structures. AB - Programs of the Sun-4 workstation permit the combined display of a table of aligned amino acid sequences of a family of proteins, and a corresponding three dimensional fold. Interactive facilities include the ability, to scroll through the sequences, to rotate the structure and to connect the examination of the sequences and the structure by selecting a portion of the sequences and automatically highlighting the corresponding region in the structure and vice versa. These programs are well suited to support applications such as the investigation of the structural or functional significance of conserved patterns of amino acids in the sequences of a family of proteins. PMID- 1913217 TI - Inferring consensus structure from nucleic acid sequences. AB - This paper presents an unsupervised inference method for determining the higher order structure from sequence data. The method is general, but in this paper it is applied to nucleic acid sequences in determining the secondary (2-D) and tertiary (3-D) structure of the macromolecule. The method evaluates position - position interdependence of the sequence using an information measure known as expected mutual information. The expected mutual information is calculated for each pair of positions and the chi-square test is used to screen statistically significant position pairs. In the calculation of expected mutual information, an unbiased probability estimator is used to overcome the problem associated with zero observation in conserved sites. A selection criterion based on known structural constraints of the strongest interdependent position pairs is applied yielding position pairs most indicative of secondary and tertiary interactions. The method has been tested using tRNA and 5S rRNA sequences with very good results. PMID- 1913218 TI - Identification of a new motif on nucleic acid sequence data using Kohonen's self organizing map. AB - Here we present a performance test of a Kohonen features map applied to the fast extraction of uncommon sequences from the coding region of the human insulin receptor gene. We used a network with 30 neurons and with a variable input window. The program was aimed at detecting unique or uncommon DNA regions present in crude sequence data and was able to automatically detect the signal peptide coding regions of a set of human insulin receptor gene data. The testing of this program with HSIRPR cDNA release (EMBL data bank) indicated the presence of unique features in the signal peptide coding region. On the basis of our results this program can automatically detect 'singularity' from crude sequencing data and it does not require knowledge of the features to be found. PMID- 1913219 TI - MCS/SEL/BAS program--an overlapping clustering method with examples from mating type interactions of ciliated protozoa. AB - The MCS/SEL/BAS program provides a method for group recognition, based on a criterion of homogeneity within the groups. The basic aim of this clustering method is not to 'force' data into a number of separate groups, as it allows the possibility that a given element in the data set can be assigned to more than one group. Moreover, a parsimonious path through the groups is sought by selecting groups on the basis of two suitably chosen, peak-ordered criteria. This selection continues until a covering of the data set is obtained (i.e., until each element in the data set is assigned to at least one group). Then relationships occurring among the set of selected groups are investigated by means of two coefficients, called overlapping and cohesion coefficient, respectively. The utility of this program has been demonstrated here in elaborating large sets of data derived from mating type interactions of ciliates, but it can be used also for analyzing data derived from a wide spectrum of compatibility phenomena exhibited by other living organisms. Algorithms of this program are written in BASIC and formulated in a conversational mode for processing on a Macintosh. A computer program (MCS/SEL/BAS) is available from G. Mancini upon request. PMID- 1913220 TI - LSTSQ: a module for reliable constrained and unconstrained nonlinear regression. AB - A software module for nonlinear regression analysis, based on the reliable Meyer Roth algorithm (a modified damped least square algorithm), is presented. It allows both constrained and unconstrained optimization, and the use of a variety of weighting methods. Virtually any nonlinear function can be fitted, including those with several nondependent variables. The package has been thoroughly tested, and is available in several common computer languages (Pascal, Modula-2 and C). It is easy to use, and advanced knowledge of mathematics or computers is not essential. Standard test problems, and a fully working example of use on enzyme kinetics are included. PMID- 1913221 TI - COOL--a VAX program for finding COmmon OLigomers in nucleic acid sequences. Thyroid hormone receptor sequences used as an example. AB - COOL is a program designed to find COmmon OLigomers in a number of nucleic acid sequences. The results of COOL serve as starting points in sequence analysis investigations as well as suggestions for polymerase chain reaction probes. As an example we analyzed thyroid hormone receptor genes and found two oligomers which are characteristic of almost all those genes. PMID- 1913222 TI - CONTROL: software for the analysis of the control of metabolic networks. AB - The program CONTROL is based on metabolic control theory and uses the method developed by Reder (1988). In this theory, two sets of parameters are defined in the vicinity of a steady-state: the elasticity coefficients which describe the local behaviour of the isolated enzymes, and the control coefficients which express the response of the whole metabolic network to perturbations at a given step. The theory shows that relationships exist between the control coefficients (summation relationships or structural relationships) and also between the two types of coefficients (control and elasticity coefficients: connectivity relationships). The program CONTROL is divided into two parts (sub-menus). The first one calculates all the control coefficients (flux and concentrations) of a metabolic network from the elasticity coefficients. Using the second menu, the symbolic relationships are obtained between the control coefficients (summation relationships) and between the control coefficients and the elasticity coefficients (connectivity relationships). These two sub-menus can be applied independently to any metabolic network (to date limited to 19 steps and 19 metabolites). PMID- 1913223 TI - Converter: a program to convert crystallographic coordinates among different molecular graphics standards on PC-IBM platforms. PMID- 1913224 TI - Materials & methods: a Macintosh hypercard stack for laboratory protocols. PMID- 1913225 TI - An X windows and UNIX implementation of our sequence analysis package. PMID- 1913226 TI - A back-step algorithm for simulation of Monod-type models. PMID- 1913227 TI - Combination chemotherapy with cyclophosphamide, fluorouracil, and either epirubicin or mitoxantrone: a comparative randomized multicenter study in metastatic breast carcinoma. AB - From February 1987 to January 1989, 60 patients with advanced breast cancer and no prior chemotherapy for advanced disease were randomized and studied, with 31 treated with fluorouracil, epirubicin, and cyclophosphamide (FEC) and 29 patients with fluorouracil, mitoxantrone, and cyclophosphamide (FNC). Doses were 500 mg/m2 fluorouracil, 500 mg/m2 cyclophosphamide, and 50 mg/m2 epirubicin2 or 10 mg/m mitoxantrone, i.v. Day 1 every 3 weeks. There were no statistically significant differences in pretreatment patient characteristics between the groups. Fifty-six patients were evaluable for response (29 in the FEC arm and 27 in the FNC arm). The response rates were 48.2% for the FEC group (complete response (CR) 10.3% and partial response (PR) 37.9%) and 40.7% for the FNC group (CR 3.7% and PR 37%) (not significantly different, NS). The median response duration was 247 and 267 days, respectively (NS), the median time to progression and time to treatment failure was 244 and 155.5 days for the FEC group and 86 and 98 days for the FNC group, respectively (NS). The incidence of nausea/vomiting was 87.1% in the FEC group and 79.3% in the FNC group, with comparable severity. Alopecia occurred in 80.6% of FEC patients and 44.8% of FNC patients (p less than 0.05). The incidences and degrees of severity of leukopenia, anemia, and cardiotoxicity were comparable in the two treatment groups. Efficacy and toxicity of the two regimens were quite similar. FNC can improve the quality of life of patients by providing significantly less alopecia. PMID- 1913228 TI - Evaluation of two consecutive regimens in advanced gastric cancer. AB - Treatment of gastric cancer still presents a challenge in cancer chemotherapy. In our Institute, from January 1981 to November 1984, 45 patients were given 5 fluorouracil (5FU) 600 mg/m2 Days 1, 8, 29, and 36; doxorubicin (A) 30 mg/m2 Days 1 and 29; mitomycin-C 10 mg/m2 Day 1 (FAM regimen) every 8 weeks. From December 1984 to October 1986, 26 patients were treated with 5FU 300 mg/m2 on Days 1-5, A 40 mg/m2 on Day 1, cisplatin (P) 100 mg/m2 on Day 1 (FAP regimen) every 3 weeks. In the FAM group, 42 patients are evaluable for response; 5 (12%) partial remission (PR), 9 stable disease (SD), and 28 progressions (PRO) were observed. Median duration of response (MDR) was 21 weeks (range 13-45) and the median survival (MS) in the whole group was 27 weeks. In the FAP group, 23 patients are evaluable: 2 CR (9%), 11 PR (47%), 2 SD (9%), and 8 PRO (34%) were observed; CR duration was 24 and 107+ weeks, respectively, MDR of PR was 22 weeks (5-35). The MS of all patients was 16 weeks. Toxicity (WHO criteria) was mild in the FAM group and severe in the FAP group. In spite of a higher objective response rate, the short MS and the severe toxicity observed in the FAP group do not merit recommendation of this regimen in patients with gastric cancer; therefore neither FAM nor FAP appear to be an ideal standard therapy. PMID- 1913229 TI - Fatal thrombocytopenia and liver failure associated with carboplatin therapy. AB - A patient with fatal severe thrombocytopenia and acute hepatic necrosis complicating carboplatin (JM8, CBDCA, NSC 241240) therapy is described. The patient, an 18-year-old man with acute lymphocytic leukemia, was given high-dose carboplatin as a part of a phase I trial of this agent for the treatment of leukemia. Carboplatin (270 mg/m2/day) was administered as an intravenous infusion on five consecutive days, and the patient died 10 days after his last dose of carboplatin from complications of thrombocytopenia and acute liver necrosis. Autopsy revealed hemorrhage into the substance of the myocardium and hemorrhagic centrilobular liver necrosis. The temporal relationship between the initial rise in this patient's liver function tests and treatment with carboplatin suggests that this patient's liver failure was in part due to carboplatin. The autopsy findings of hemorrhage into the substance of the myocardium and centrolobular liver necrosis suggest that, in addition to its direct effects, carboplatin may have also contributed indirectly to this patient's liver failure through the complications of thrombocytopenia. PMID- 1913231 TI - Lasers in surgical oncology. PMID- 1913230 TI - Cells of chemically induced tumors differentially express major histocompatibility complex class I antigens. AB - Several recent studies have indicated that alterations in expression of major histocompatibility complex (MHC) antigens by tumor cells affects the ability of the host to mount an effective antitumor immune response. To investigate whether newly induced tumors frequently exhibit altered MHC antigen expression, we used methylcholanthrene to induce a series of tumors and elevated MHC antigen expression by these cells. The tumors exhibited a variety of MHC phenotypes in vitro. The nature of their phenotypes suggested that these cells were, in fact, capable of independent and abnormal regulation of MHC class 1 genes. However, when maintained in vivo, these same tumor cells expressed measurable levels of all of the appropriate MHC class I antigens. Thus, newly induced tumor cells are capable of abnormal MHC class I antigen expression. However, there was no obvious correlation between the phenotypes exhibited by these tumor cells in vitro and either their phenotype or their tumorigenic potential in vivo. PMID- 1913232 TI - Insertional mutagenesis: neoplasia arising from retroviral integration. AB - The integration of retroviral proviruses near cellular genes can profoundly affect their expression. Painstaking analysis of insertion sites from a large number of tumors has revealed a number of previously unknown proto-oncogenes, and has elucidated new mechanisms whereby known proto-oncogenes can be activated. A number of these genes have been implicated in tumors of clinical relevance. At the time of writing a great deal remains to be learned of the normal function of these genes in the cell. While it has yet to be demonstrated that retroviral insertion mechanisms play some role in naturally occurring human neoplasms, they must be considered in the context of retroviral gene therapy protocols now being contemplated. PMID- 1913233 TI - Antitumor properties of phenothiazines. AB - The purpose of this review is to describe and evaluate the antineoplastic properties of phenothiazines. The present research studies suggest that many phenothiazines do not show significant antitumor and antineoplastic activity and so they cannot be used as potential drugs to treat cancer. However some of their derivatives help indirectly in decreasing cytotoxic effects caused by radiation and other chemical carcinogens. Additionally, some phenothiazine derivatives provide protection against cancers caused by metabolic activation of carcinogens such as dimethylbenzanthracene. The selective accumulation of phenothiazine derivatives in certain tissues such as brain and melanoma tumors may provide an effective treatment of such tumors. Current studies suggest that highly potent phenothiazine derivatives can be made by nitro substitution on the aromatic ring of phenothiazines. PMID- 1913234 TI - Introduction to series on growth factors. PMID- 1913236 TI - [Role of age at the moment of irradiation on the induction of tumors]. AB - The probability that rats develop tumours following a 3 Gy exposure to gamma rays from cobalt 60 was observed to depend on age at exposure. Lifetime excess of neoplasia decreased by a factor of about 10 in 9-month-old rats as compared to animals irradiated in utero. The 3-month age group developed slightly fewer tumours than the group irradiated in utero, and tumour location was different. The higher incidence of tumours observed in the foetal group was mainly due to the high sensitivities of central nervous system and gonads during organogenesis. PMID- 1913235 TI - Transforming growth factor-beta--mullerian inhibiting substance family of growth regulators. PMID- 1913237 TI - [Chromosome hyper-radiosensitivity in mice at the end of pregnancy]. AB - Irradiation of mice with 2 Gy of gamma-rays at various times of pregnancy induces a threefold increase in the rate of chromosome breaks in spontaneously dividing bone marrow cells from the 16th to 19th days. This high sensitivity disappears shortly after delivery, and it is even possible that a hyposensitivity develops at this time. The causes of this phenomenon remain unknown, but since it occurs shortly after the high increase of oestrogen and progesterone hormones, a direct relationship may exist. PMID- 1913238 TI - [Use of codons in plant lectins]. AB - Codon usage in the coding region of mature lectins has been examined for 11 plant species (8 leguminoseae, 1 euphorbiaceae, 2 gramineae). The different legume lectins exhibit nearly the same codon usage pattern whereas the choice for the silent position of codons is non-random. PMID- 1913239 TI - [Synthesis and pharmacological study of radioiodinated serotonin derivative specific of 5-HT1B and 5-HT1D binding sites of the central nervous system]. AB - We describe here the synthesis of a new serotonin conjugate, S-CM-GTNH2, and its radioiodinated derivative. Quantitative autoradiographic studies on rat and guinea pig brain sections incubated with 2 nM [3H]5-HT showed a preferential affinity of S-CM-GTNH2 for 5-HT1B and 5-HT1D sites. Autoradiograms from brain sections incubated with 0.02 nM S-CM-G[125I]TNH2 showed a heterogeneous anatomical distribution of the labelling with high densities in regions rich in 5 HT1B or 5-HT1D binding sites, and with no labelling of those rich in 5-HT1A or 5 HT1C sites. The pharmacological profiles of the binding sites corresponded to those of 5-HT1B and 5-HT1D receptor subtypes. The radioligand S-CM-G[125I]TNH2 is a good probe for the study of these sites and will be used for their subcellular localization in electron microscopy. PMID- 1913240 TI - [Do the variations in water carbon dioxide pressure and PH have an effect on the nature of end products of protein catabolism, ammonia and urea, in the clawed frog Xenopus laevis?]. AB - The effects of PCO2 and pH changes in the ambient water on the nitrogen catabolism and the proportions of the excreted nitrogenous end products, ammonia and urea, were studied in the clawed frog, Xenopus laevis, at 24 degrees C. In animals living in artificial fresh water, the exposure to a hypocapnic alkalosis (PCO2 = 0.7 Torr instead of 10 Torr) did not entail any change in the nitrogen catabolism. In animals who lived in a water loaded with NaCl and had therefore a higher oxygen consumption, an intense nitrogen catabolism and a marked ureotelism, the hypocapnic alkalosis seems to have increased the intensity of the nitrogen catabolism. In neither group were there signs of ammonia toxicity. PMID- 1913241 TI - [Functional inactivation of centrosome of mouse 3T3 cells by heat shock]. AB - The microtubule assembly capacity of centrosome has been tested in mouse 3T3 cells. Following heat shock (30 min. at 43.5 degrees C), centrosomes display a total lack of microtubule nucleation. This stress leads to functional arrest of the organelle. The natural control of the activity of the centrosome is therefore questionable. PMID- 1913242 TI - [Dissociation between peripheral and central components of tolerance to behavior effects of interleukin-1 in rats]. AB - Interleukin-1 (Il-1) is an endogenous pyrogen which is released by accessory immune cells and which has potent neural effects. Rats implanted subcutaneously with an osmotic mini-pump delivering 2 micrograms Il-1 per day rapidly became tolerant to the behavioral and toxic effects of this cytokine. Acute challenge with Il-1 reversed this tolerance when the cytokine was injected intraperitoneally (3 micrograms/rat) but not when it was injected into the lateral cerebral ventricle (3 ng/rat). These results suggest a differential regulation of the peripheral and central receptors mediating the effects of Il-1. PMID- 1913243 TI - [Method for measuring sensitivity to periodic spectral energy modulations in human]. AB - The distribution of spectral energy of a visual stimulus can be subject to Fourier analysis. In this perspective, we have built a device which produces periodic variations in energy (square waves) over the visible spectrum (400-700 nm), and where the amplitude, phase and frequency of the stimuli can be independently controlled. From the non-modulated spectrum, supplying a white spot, for a given frequency and phase, there is a minimal amplitude modulation (contrast threshold) for which the spot becomes chromatic. As an illustrative example we present here a curve of optimal sensitivity values (inverse of contrast) as a function of frequency (from 0.5 to 3.6 cycles/300 nm) for a normal subject. PMID- 1913244 TI - [Androgen-dependent protein secreted by mouse caput epididymis shows high homologies with different glutathione peroxidases]. AB - Principal cells of the mouse caput epididymidis synthesize and secrete a 24 kDa protein able to bind to the head of the spermatozoa. Sequencing of several clones selected from cDNA and genomic libraries, combined with the microsequencing of the NH2 terminus of the protein allowed to reconstitute the entire primary structure of the mature 24 kDa protein. It revealed 81% homology with a human plasma glutathione peroxidase and 61% homology with a mouse erythrocyte glutathione peroxidase. This enzyme, once secreted in the epididymal fluid, might protect sperm membrane lipids, particularly those of the acrosomal part, against peroxidation. PMID- 1913245 TI - Does protein kinase C require Ca2+ for activation? AB - Ca2+ requirement for protein kinase C activation is a matter of controversy. In this report we have examined Ca2+ dependency of the reaction in different assay systems and shown that the enzyme response to Ca2+, as well as diacylglycerol, depends upon phospholipid species, protein substrate and lipid conformation (micelles or sonicates). These results emphasize that the enzyme characteristics as defined in reconstituted membrane systems may not have a physiological relevance. PMID- 1913246 TI - [Mitogenic activity of vasculotropin for peripheral human lymphocytes]. AB - Vasculotropin is a growth factor with a unique specificity for vascular derived endothelial cells. We report that normal human peripheral lymphocytes represent another target for vasculotropin. The mitogenic activity of the medium conditioned by these cells cultured in the presence of Concanavalin A is potentiated by vasculotropin. This effect is exerted more likely through interactions with the soluble mediators rather than through the VAS receptors since VAS binds equally to Concanavalin A stimulated and to unstimulated lymphocytes. PMID- 1913247 TI - A physical model for motor proteins. AB - A general stochastic theory is outlined for chemical to mechanical energy transduction by motor enzymes. In addition to ATP hydrolysis and fiber binding phenomena, thermal noise effects are taken into account. A minimal, 4-state model is identified that gives the hydrolysis rate as well as mechanical quantities such as sliding velocity and generated force, as functions of ATP concentration and the number of motors. It explains in a unified way many results of recent in vitro assays, both in myosins/actin and kinesins or dyneins/microtubule systems. PMID- 1913248 TI - [Three-dimensional model of cancer and in vitro metastasis: application to non Hodgkin malignant lymphoma]. AB - In vitro cancer studies require models more appropriate than the standard monolayer cultures of tumoral cell lines. This report describes the production of an in vitro three-dimensional rebuilt tumor using a non-hodgkin malignant lymphoma. The model exploits the relationship between angiogenesis and cancer formation by employing both tumor cells and fusiform cells derived from an angioma. The significance of this model, which has also been used with malignant melanoma cells, is that the rebuilt tumor, when placed in culture, produces many tumorous nodules which are fixed to a sub-layer of fusiform cells and newly secreted matrix. These are, in effect, in vitro metastases. The ultrastructural aspect of this neomatrix indicates its proteoglycan nature. The micro-environment formed by the vascular cells and matrix appears to be critical for the production of metastases. PMID- 1913249 TI - [Molecular modelling of glycans: three-dimensional structure and protein fraction interaction. The example of rabbit sero-transferrin]. AB - On the basis of experimental data and of computer calculations using the Tripos 5.3 force field in order to examine the three-dimensional structures which are sterically feasible and the conformations which are energetically the most favourable, we have designed a program of molecular modelling of biantennary glycans of the N-acetyllactosaminic type (complex type). We demonstrate that, in absence of any interaction with the protein, a high number of glycan conformations exists which can be classified into five basic conformations, four of which have already been described. In fact, in addition to the Y-, T-, "bird" and "broken-wing" conformations, a "back-folded wing" conformation is energetically feasible. In contrast, the glycan linked to the protein is immobilized into only one conformation: the "broken-wing" conformation. Forming a bridge between the two lobes of the peptide chain, it probably contributes to the maintenance of the protein in a biologically active conformation. PMID- 1913250 TI - [Increase of the number of oogonia in the ovary of fetal rabbit hypophysectomised by decapitation. Probable role of thymus]. AB - A significant increase in ovarian volume and in the numbers of germ cells was observed in rabbit foetuses hypophysectomised by decapitation on day 19 and killed on day 28 when compared with unoperated females of the same litter. It seems that the hypophysis acts indirectly while the foetal thymus has a likely direct role. PMID- 1913251 TI - [A statistical model of evolution with stabilizing selection]. AB - We consider a population of fixed size and reproducing asexually, evolving in a rugged fitness landscape. Selection takes place only via the elimination of individuals with unfit genomes. Unfit genotypes are distributed at random in genotypic space. The genetic structure of the population and the speed of genetic drift are explicitly computed in the infinite genome limit. PMID- 1913252 TI - [Purification and characterization of precursors of mouse protamine mP2]. AB - Mouse protamine 2 (62 residues) is synthesized as a precursor pmP2 (106 residues) which is subsequently processed during the end of spermiogenesis. Three proteins with molecular and electrophoretic properties similar to those of pmP2 were isolated from testis purified nuclei. The comparison of their amino acid composition and of their N-terminal sequence with those of pmP2 shows that the three isolated proteins are products of pmP2 precursor processing. The three intermediate proteins pmP2/5, pmP2/11 and pmP2/20 which contain 102, 96 and 87 residues respectively, are generated from pmP2 precursors after N-terminal excision of 4, 10 and 19 residues, respectively. PMID- 1913253 TI - [Does synaptic elimination contribute to the organization of cerebellar microzones of climbing fiber projection?]. AB - In adult rats whose cerebellar Purkinje cells (PCs) remain polyinnervated by olivary climbing fibres (CFs) after postnatal irradiation, topographical maps of responsive PCs to mechanical stimulation of the third row of contralateral vibrissae show that these cells are more numerous and more diffusely distributed than in the normal rat. PCs responding with the "best responses" are distributed evenly from the midline to 400 microns lateral in the contralateral hemivermis of lobule VII, and not in a parasagittal microzone centred on the plane 200 microns as in the normal rat. Thus it seems likely that synaptic elimination should contribute to microzone formation during postnatal development of the normal cerebellum. PMID- 1913254 TI - [IIa/IIo conversion of RNA polymerase II during heat shock]. AB - Heat-shock treatment of cells activates a protein kinase which phosphorylates a heptapeptide analogous to the repeated motif of the C-terminal domain (CTD) of the large subunit of RNA polymerase II from mammalian cells. This is corroborated with a modification of the large subunit of this enzyme during thermal stress in HeLa cells. We have observed a shift from the IIa form (unphosphorylated) to the IIo form (phosphorylated) with a higher apparent molecular weight, during a heat shock at 44, 45 or 46 degrees C and by a chemical stress induced by sodium arsenite. RNA polymerase II hyperphosphorylation, together with the activation of the heat-shock transcription factor, might contribute to the onset of the preferential transcription of heat-shock genes. PMID- 1913255 TI - [Vectorisation of doxorubicin in nanospheres and reversion of pleiotropic resistance of tumor cells]. AB - A multidrug resistance human cell line (Dox-R-MCF7), originating from mammary adenocarcinoma was compared to the drug sensitive parent line (MCF7) to determine whether or not the use of doxorubicin-loaded biodegradable nanospheres (NS-Dox) could circumvent drug resistance. The Dox-R-MCF7 line was shown to resist free doxorubicin (Dox) as the 50% lethal dose for them was 150 times higher than for the sensitive cell-line. Isohexylcyanoacrylate nanospheres, porous matrices of biodegradable innocuous polymer, diameter 300 nm, were loaded with doxorubicin. Free Dox, NS-Dox and Dox-free polymer (NS) were added to the culture medium for 6 hrs. In terms of 50% lethal dose, NS-Dox were cytotoxic for the resistant cell line to an identical extent as for the sensitive parent line. Dox-free nanospheres alone or mixed with free-Dox were noncytotoxic for the resistant line. Drug targetting could be of main importance to overcome multidrug resistance. PMID- 1913256 TI - [Identification of Cajal-Retzius cells during neocortical ontogenesis in mice with fluorescent carbocyanine]. AB - Cajal-Retzius cells, which are present transiently in the first layer of the mammalian neocortex, have been revealed in the mouse by DiI. This lipophilic fluorescent dye, locally applied over the cortex after formaldehyde fixation, allowed the global view of cortical cells. During ontogenesis, Cajal-Retzius cells retained their initial characteristic bipolar shape and orientation parallel to the meningeal surface. The bright fluorescent light emitted by this dye allowed visualization of the labelled cells by "microtomoscopy" using a confocal scanning laser microscope and analysis of the detailed aspect of these neurons and of their connections. PMID- 1913257 TI - [Study by NMR and circular dichroism of synthetic "zinc finger" peptide of viral Gag protein from HIV-2]. AB - We report the synthesis in solid phase of an 18-amino acid peptide that contains the cysteine-rich region of the structural Gag protein of HIV-2. The characterization of this fragment and of its interaction with Zn2+ has been made by one- (1 D) and two-dimensional (2D) NMR techniques and by circular dichroism. Our results suggest that in aqueous solution the complexation produces a significant perturbation in the conformation of this peptide. PMID- 1913258 TI - [Analysis of kinetics of consecutive metabolic cerebral activations induced by spatial discrimination testing, using (14C)-glucose, in an eight-arm radial maze in mice]. AB - Regional mapping of relative (14C)-glucose (GLU) uptake was analyzed in Balb/c mice at 3 time intervals (5 min., 1 hr., 3 hrs.) after either the first (Day 1) or the last (Day 9) daily sessions of a spatial discrimination testing procedure in an eight-arm radial maze. On Day 1, increased labelling was found 5 min. post training in subcortical, hippocampal and cortical regions. Decreased GLU uptake was observed 1 hr. later in the same regions, followed at 3 hrs. post-training by a retarded activation in the above areas and particularly in thalamic and cortical structures. On Day 9, there was only an early (5 min.) post-training increase in metabolic activity followed by a subsequent monotonic decrease over 3 hrs. post-training period. PMID- 1913259 TI - [In vivo and in vitro study of the action of dopamine on oocyte growth and juvenile hormone production in Blattella germanica (L.) (Dictyoptera; Blattellidae)]. AB - In vivo, within the first ovarian cycle of B. germanica, dopamine (1 microgram/cockroach) enhanced oocyte growth when injected on day 1 or 2, just before vitellogenesis, whereas it induced the inverse effect on day 6-7, at the end of vitellogenesis. In vitro, dopamine (10(-4) M) stimulates juvenile hormone production by incubated corpora allata from 2-day-old females, and inhibited it on 6-day-old glands. The physiological significance of these effects is discussed. PMID- 1913260 TI - [Presence of neuritic plaques and neurofibrillary changes in the cerebral cortex of an aged lemuride primate]. AB - Some aged Microcebus murinus brains (8 to 11-years old animals) displayed a dramatic atrophy particularly in the neocortex, hippocampus, basal ganglia, hypothalamus, brainstem and cerebellum, associated with a conspicuous increase in the size of the cerebral ventricles. These morphological changes were accompanied by certain histological profiles indicative of pathology. In the cortex, these histological changes consisted of (1) a large number of neuritic plaques formed by degenerated neurites sometimes surrounding an amyloid plaque, (2) dense bundles of argyrophilic filaments in many pyramidal neurons, and (3) amyloid deposits in and around the vascular walls. So far these preliminary studies cannot prone that this degeneration is similar to the human senile dementia of Alzheimer's type, but they may indicate that Microcebus murinus may well be a good model to study cerebral aging, providing comparisons with humans. Furthermore, the size, life span and cost of this species provide further advantages over other nonhuman primates. PMID- 1913261 TI - Platelet and clotting abnormalities in asthma. PMID- 1913262 TI - Lymphokines in asthma: are they there and can they be detected? PMID- 1913263 TI - Delayed generation of thrombin in clotting blood of atopic patients with hayfever and asthma. AB - There have been several reports on alterations of platelet function and raised plasma heparin levels in symptom-free atopic subjects. Either of these can affect formation of thrombin in vivo. In 25 symptom-free atopic patients and 32 healthy volunteers we studied the generation of thrombin in blood emerging from a standardized skin microvasculature injury, which also served to determine bleeding time. Generation of thrombin was delayed in atopics. They produced significantly less thrombin (P less than 0.01) during the early and central phase of haemostasis. The amount of thrombin generated was inversely correlated to bleeding time, which in atopics was on average 50 sec longer than in controls (P = 0.055). Two hours after ingestion of 500 mg aspirin, this difference increased up to 150 sec, although the individual responses varied markedly (P = 0.08), while the generation of thrombin became strongly depressed in both groups. The possible clinical relevance of the delayed formation of thrombin in atopy awaits further studies. PMID- 1913264 TI - Neopterin quantification in acute severe asthma. AB - To investigate the pathogenic role of cell-mediated immunity (CMI) in acute severe asthma, 10 patients with acute asthma requiring admission to hospital had measurements of serum and urine absolute neopterin and neopterin/creatinine ratios. Serum was collected upon entry to hospital, 24 hr later and at 2 weeks; and urine at 24 hr and at 2 weeks after admission. Comparisons were made with 12 stable asthmatic patients, healthy control subjects, and six renal transplant patients undergoing transplant rejection. In contrast to the renal transplant patients who demonstrated T-lymphocyte-macrophage activation, neopterin concentrations and neopterin/creatinine ratios in both acute and stable asthmatic patients were not elevated. We have not found functional evidence that CMI participates in the pathogenesis of acute severe asthma. PMID- 1913265 TI - Nasal challenge studies with bradykinin: influence upon mediator generation. AB - Previous studies have shown that nasal allergen provocation leads to dose dependent increases of inflammatory mediators, e.g. histamine, kinins, LTC4 and PGD2 in nasal lavages. To investigate further the interaction of these mediators, a titration study with intranasal bradykinin (Bk) application (maximal dose 100 nmol/nostril) and consecutive lavage were performed in eight grass-pollen allergic patients out of season, and five controls. The nasal lavages were analysed for albumin, N-alpha-tosyl-L-arginine methyl ester (TAME) esterase activity, histamine, 9 alpha,11 beta-PGF2, and LTC4. The clinical reactions were measured with a subjective symptom score. A dose-dependent elevation of albumin was found which was significantly higher in patients with allergic and non allergic rhinitis compared with normal volunteers. TAME-esterase activity also increased in relation to the dosage of Bk given without significant difference between the various groups. No influence on histamine, LTC4 and 9 alpha,11 beta PGF2, release (PGD2 metabolite) was seen. Short-lasting clinical symptoms like irritation, sneezing, and obstruction were noticed after the two highest Bk dosages (10 and 100 nmol). We conclude that intranasally applied Bk induces a dose-dependent plasma leakage into the nasal cavity, which is significantly higher in patients with seasonal allergic rhinitis out of season compared to normals. Bk does not seem to affect the mast cell since histamine, LTC4 and 9 alpha,11 beta-PGF2 levels do not alter. The ability to induce relevant symptoms of rhinitis provides strong support for the hypothesis that kinins may be important mediators of inflammatory disorders of the upper airways. PMID- 1913266 TI - Exposure and sensitization to dust mite allergens among asthmatic children in Sao Paulo, Brazil. AB - A group of 20 mite allergic asthmatic children aged 6-12 years old, living in Sao Paulo, Brazil, was studied regarding their degree of sensitization to house dust mites and exposure to mite allergens in their homes. In 18 out of 20 houses at least one dust sample was obtained which contained greater than 10 micrograms Der p I/g of dust. The highest levels of Dermatophagoides pteronyssinus allergens, Der p I and Group II, were measured in bedding samples (geometric mean 38.4 and 36.6 micrograms/g, respectively), followed by bedroom floor, TV room and kitchen. Mite allergen levels in Brazilian houses were as high as those reported to be associated with sensitization and acute attacks of asthma in other parts of the world. In keeping with previous reports that D. farinae is rarely found in Brazil, Der f I was undetectable or found in very low levels (less than 0.5 micrograms/g). Levels of cat allergen Fel d I of greater than 8 micrograms/g of dust were obtained only in 2 houses only. Cockroach allergen Bla g I was detected in five out of 20 houses. Levels of IgE antibodies to D. pteronyssinus were greater than 200 RAST U/ml in 19 out of 20 children (geometric mean 1588 RAST U/ml). IgE antibodies to cat, cockroach, A. fumigatus, ragweed and rye grass pollens were undetectable or less than 80 RAST U/ml. IgE antibodies to the mite Blomia tropicalis were also measured, and levels greater than 200 RAST U/ml were observed in 13 out of 20 sera.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1913267 TI - Domestic endotoxin exposure and clinical severity of asthma. AB - Endotoxins are potent pro-inflammatory substances present in several natural environments and in commercial house dust extracts. To investigate the possible effect of chronic endotoxin exposure on asthma, 28 patients with perennial chronic asthma (20 allergic to house dust mite and eight intrinsic asthmatics) were evaluated during a 4-month period (lung function, clinical and immunological criteria). At the same time, two house dust samples were collected from each patient's home to determine total house dust weight (mg/m2), endotoxin concentration and house dust mite antigen content (evaluated indirectly by guanine content with HPLC method). The mean (+/- s.d.) endotoxin concentration, as measured by quantitative Limulus assay was 2.59 (+/- 3.41) ng/mg house dust, ranging from 0.12 to 20 ng/mg. The mean guanine content was 0.13 (+/- 0.16) mg/100 mg house dust. There was no correlation between endotoxin and house dust mite concentrations. Patients were compared according to the low or high grade exposure to dust, endotoxins and guanine. Compared with patients with low grade (less than or equal to 5.6 ng/ml) exposure, subjects exposed to high endotoxin concentrations (greater than 5.6 ng/ml) showed a significant increase in dyspnea (median 2.6 vs 3.3; P less than 0.05) and treatment (median 14 vs 44.3; P less than 0.01) scores, oral corticosteroid (median 0.0 vs 13.5 mg/24 hr; P less than 0.01) and beta 2-mimetics (median four vs eight puffs/day; P less than 0.01) intake, and a significant decrease in FEV1/FVC (median 84.5 vs 67% of predicted value; P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1913268 TI - Isolation and partial characterization of Bermuda grass pollen allergen, BG-60a. AB - In an earlier study we showed that Bermuda grass (Cynodon dactylon) pollen contains at least 12 IgE-binding proteins that can be analysed by immunoblot technique. One of the active components (BG-60) proved to be a basic protein of glycoprotein nature. It contained about 28% carbohydrate as determined from the dry weight and consisted of four molecules. One of the components was purified from the pollen extract by a combination of ammonium sulphate precipitation, ion exchange chromatography on carboxymethyl-TSK, gel filtration on Ultrogel AcA 44 and chromatofocusing. Its molecular weight was approximately 60 kD by SDS-PAGE and 34 kD by gel filtration chromatography. The isoelectric point of the antigen was about 9.7. The homogeneity of the antigen BG-60a was assessed by one single arc of immunoprecipitation both in immunodiffusion and crossed immunoelectrophoresis and by one single band after SDS-PAGE. Its allergenicity was demonstrated by direct intradermal skin test on allergic patients and by examining IgE-binding reactivity with allergic patients' serum. PMID- 1913270 TI - Neonatal IgE: a poor screen for atopic disease. AB - Screening for atopic disease using neonatal serum IgE has been advocated on the basis of the predictive value of elevated levels. However, this is only one measure of validity. The test was validated fully in 92 infants with a bi parental history of atopy using 0.7 IU/ml as the cut-off. All infants were assessed prospectively for evidence of atopic disease (eczema, recurrent wheezing or food reactions) and skin-prick test positivity in the first year. Total serum IgE was measured by ultrasensitive ELISA on 61 cord blood samples and 92 samples taken at 7 days. All cord samples were re-analysed by PRIST and the first 33 by ultrasensitive RIA giving, respectively, 82% and 94% concordance (regarding undetectable, detectable and elevated levels) with ELISA. Maternal contamination was indicated in 7% of cord samples by high serum IgA. Ninety-five per cent of cord/7-day IgE pairs showed no change or minor rises at 7 days. Forty-nine per cent of the infants had evidence of atopic disease. Only 5% had elevated 7-day IgE. The positive and negative predictive values of the 7-day test were 60% and 52%, respectively, and specificity 96% but the sensitivity was only 7%. High levels did not distinguish the infants with the most unequivocal evidence of disease, i.e. eczema with a positive skin test. In conclusion IgE at 7 days is comparable to and more reliable than cord IgE. However, neonatal IgE screening is too insensitive to have clinical application. PMID- 1913269 TI - Regulation of the human immune response to ragweed pollen by immunotherapy. A controlled trial comparing the effect of immunosuppressive peptic fragments of short ragweed with standard treatment. AB - A new allergenic preparation consisting of peptic fragments of short ragweed has been tested for its clinical effectiveness. Such enzymatically derived fragments have been shown in prior murine studies to retain the T epitopes of the original allergen but to have a severe reduction in the number of B epitopes. Three groups of ragweed hayfever patients were placed on pre-seasonal immunotherapy. One group received a conventional ragweed preparation that had been enriched for antigen E (Amb a I), designated as Pool 2. The second group was given fragments of Pool 2 (fSRW) prepared by peptic digestion and the third group was injected with histamine as a placebo. Groups treated with the fSRW and Pool 2 had significantly reduced symptom-medication scores compared with the placebo-treatment group. However, fSRW-treated patients fared significantly better than Pool 2 patients (P less than 0.02). fSRW injections caused a significant rise in preseasonal specific IgG, antibodies as well as suppression of the seasonal anamnestic specific IgE increase. Similar, but not quite as marked changes occurred with Pool 2 treatment. fSRW was well tolerated and non-toxic. Thus, allergen modification by enzymatic degradation, as demonstrated here, appears to be a promising new approach for allergen immunotherapy. PMID- 1913271 TI - Relative risks of bronchial hyper-responsiveness associated with skin-prick test responses to common antigens in young adults. AB - We studied 143 young subjects by skin-prick testing to common allergens and by the measurement of non-specific bronchial responsiveness (NSBR). A logistic regression model showed a prevalence odds ratio (POR) for bronchial hyper responsiveness (PD20 less than 10 mumol methacholine) in house dust positive subjects of 4.10 (95% CI 1.77-9.51, P less than 0.001), and in mould positive subjects 5.72 (95% CI 2.06-15.9, P less than 0.001): the PORs for epithelia (2.05, P = 0.12) and grasses (1.78, P = 0.19) were not significant. If bronchial reactivity was assessed as measurable (PD20 less than 102 mumol methacholine) or not, the POR for house-dust-positive subjects was 4.83 (95% CI 2.23-10.5, P less than 0.001), for moulds was 10.5 (95% CI 2.33-47.5, P less than 0.001), for epithelia was 4.79 (95% CI 1.91-12.0, P less than 0.001), and for grasses was 2.21 (95% CI 1.11-4.4, P = 0.022). The results show the risk of bronchial hyper responsiveness is greater in subjects sensitive to house dust and mould than in those reactive to grasses, and suggests that the presence or absence of increased NSBR in atopic individuals may depend on the antigens to which they become sensitized. PMID- 1913272 TI - Evidence for IgE immune complexes and distribution of IgG subclasses with anti IgE activity in patients with atopic dermatitis. AB - The anti-IgE autoantibody was detected, using a radioimmunoassay, in 17 out of 35 (48.6%) of patients with atopic dermatitis. Significant increased levels of IgG anti-IgE were seen in the patients studied compared with the control group. The specificity of the anti-IgE autoantibody was confirmed by competitive inhibition assay using IgG, IgM, IgE myeloma. A correlation was observed between the levels of IgG-anti-IgE and serum IgE but not between the IgG subclasses with anti-IgE activity and the clinical status. These data demonstrate that the IgG subclass distribution with anti-IgE activity belongs mostly to the IgG1 and IgG4 subclasses compared with the controls. Moreover, ultracentrifugation analysis indicated that the IgG-anti-IgE in the serum samples from the patients with atopic dermatitis was present in the form of an immune complex with self-IgE. These observations may suggest that the anti-IgE complexes may play a broader role in the modulation of the immune response and that this autoantibody may mask recognition of IgE in conventional assays. PMID- 1913274 TI - Immunoblot multi-allergen inhibition studies of allergenic cross-reactivity of the dust mites Lepidoglyphus destructor and Dermatophagoides pteronyssinus. AB - The allergenic similarity of the pyroglyphid mite D. pteronyssinus and the glycyphagid mite L. destructor was investigated with a new immunoblotting inhibition technique allowing simultaneous comparison of several allergens. Extracts of D. pteronyssinus and L. destructor were separated by SDS-PAGE and electroblotted to nitrocellulose (NC). A serum pool containing IgE specific to the major allergens in both mites was mixed with serially diluted extracts of D. pteronyssinus and L. destructor and incubated with the mite allergens of NC. The inhibition of the IgE binding to NC was evaluated by densitometric scanning and percentage inhibition was calculated. The IgE antibodies to the 25-kD component in D. pteronyssinus, were inhibited to the same degree by extracts of D. pteronyssinus and L. destructor. Another major allergen component in D. pteronyssinus (16 kD) was also inhibited by L. destructor extract but to a lesser degree: 400 times more of the heterologous than of the homologous extract was needed for 50% inhibition. To produce 50% of heterologous inhibition of the two major allergen components at 15 and 53 kD of L. destructor, 2000 and 10,000 times more respectively, of D. pteronyssinus than of L. destructor extract were needed. Two minor allergen components of L. destructor showed some cross-reactivity with D. pteronyssinus. However, L. destructor was a stronger inhibitor of D. pteronyssinus than vice versa, probably because the sera were obtained from persons more sensitized to L. destructor than to D. pteronyssinus. PMID- 1913273 TI - Do diagnostic procedures other than inhalation challenge predict immediate bronchial responses to inhaled allergen? AB - To investigate the relationships between allergen inhalation challenge and other diagnostic procedures, inhalation challenge with house dust (HD) allergen, intradermal skin tests with HD allergen, inhalation challenge with methacholine and circulating HD allergen-specific IgE levels were examined in 104 patients with bronchial asthma. Using the single exposure method, allergen inhalation challenge was performed. Forty-three patients had positive bronchial responses to allergen and 61 patients had negative bronchial responses. With serially diluted HD allergen (10(-3) to 10(-6), w/v), skin-test sensitivity was expressed as the highest dilution required to produce a weal of more than 9 x 9 mm. With the continuous exposure method, bronchial responsiveness to methacholine was evaluated as the number of units of inhaled methacholine (PD35-Grs) from the start to the point at which Grs had decreased by 35% from its baseline value. The level of circulating HD allergen-specific IgE was measured with the Phadebas RAST system and the results were assessed as a RAST score. Using discriminant analysis, in which the independent variables were skin-test sensitivity, PD35-Grs and the RAST score, only in 30% of all patients was bronchial responsiveness to inhaled HD allergen predictable. Therefore, we suggest that inhalation challenge with allergen is an essential test for determining the role of a specific allergen in airways at present. PMID- 1913275 TI - The nasal allergic reaction: observations on the role of histamine. PMID- 1913276 TI - The nasal mast cell and rhinitis. PMID- 1913277 TI - Mast cell behaviour in symptomatic patients with eye and nose allergies. PMID- 1913278 TI - Biological properties of human skin mast cells. AB - Mast cells and basophils, although sharing many constitutive properties, are quite distinct in their development, functions and biological properties. Mast cell granules are composed of a macromolecular matrix of proteoglycan and neutral protease of which heparin and tryptase, respectively, are predominant. The distribution of the other major neutral protease, chymase, allows human mast cell subpopulations to be subdivided immunocytochemically. All human mast cells respond to IgE-dependent stimulation with the secretion of the preformed mediator, histamine, and the newly generated lipid-derived eicosanoids PGD2 and LTC4. Although amounts of these products vary between mast cells dispersed from different tissues, it is uncertain whether this reflects true heterogeneity. Mast cells of the human skin, but not those of other tissues, are sensitive to stimulation by substance P, compound 48/80 and other basic non-immunological stimuli. The mechanism of mediator secretion induced by these agents is distinct from that induced by IgE-dependent stimulation. However, the morphological characteristics of degranulation are similar, suggesting that the distinct biochemical pathways merge into a common pathway before effecting degranulation. PMID- 1913279 TI - The mast cell and its function in allergic disease. PMID- 1913280 TI - Biological properties of eosinophils. PMID- 1913281 TI - Current understanding of the role of the eosinophil granulocyte in asthma. PMID- 1913282 TI - [Socio-economic differential mortality in the post-modern French society]. PMID- 1913283 TI - [Fatal traffic accidents]. PMID- 1913284 TI - [Socio-occupational future of patients treated for myocardial infarction]. PMID- 1913285 TI - Staff perception of work climates at five health stations. PMID- 1913286 TI - [Medical education in Germany under the Nazi regime]. PMID- 1913287 TI - Bone mineral density of the spine in normal Japanese subjects using dual-energy X ray absorptiometry: effect of obesity and menopausal status. AB - Bone mineral density (BMD) of the lumbar spine was measured to determine normal Japanese values and to examine the effect of obesity and menopausal status on BMD. Normal Japanese subjects (N = 1,296, 1,048 women and 248 men) were examined using dual-energy X-ray absorptiometry. BMD for men peaked between age 20 and 29. For women, there was abrupt bone loss after age 50. Obese women within the same age bracket had a higher BMD than thin women after age 40-49. We determined that BMD began to decline during the irregular menstruation period before the onset of menopause. We conclude that there is a positive correlation between obesity and BMD, particularly in postmenopausal women. In addition, we found that bone loss related to menopause begins during the irregular menstruation period before menopause. PMID- 1913288 TI - Ultrasound transmission measurements through the os calcis. AB - A method of measuring ultrasonic propagation in the os calcis was devised for assessing bone properties in humans. Speed-of-sound (SOS) and broadband ultrasound attenuation (BUA) were measured using broadband acoustic pulses transmitted and received by a pair of focused transducers. The transducers are mounted coaxially in a water tank with the subject's heel in between. Reproducibility of results in an adult male was 10% for the BUA and 1.2% for the SOS. Both SOS and BUA changed when the transmission path through the os calcis was varied. For a population of normal male subjects, SOS and BUA were correlated with densitometry results on the os calcis, but less well correlated to area density at remote sites. PMID- 1913289 TI - Influence of brisk walking on the broadband ultrasonic attenuation of the calcaneus in previously sedentary women aged 30-61 years. AB - The amount and type of exercise needed to maintain or increase bone density in women is unclear. The purpose of the present study was to examine the influence of brisk walking on broadband ultrasonic attenuation (BUA) values for the calcaneus in formerly sedentary women aged 30-61 years (mean 44). Twenty-five women followed the program of brisk walking for 1 year and 15 acted as controls. The walkers completed an average (SEM) of 159 (46) minutes/week of brisk walking at a speed of 1.72 (0.05) meters/second, i.e., about 16-18 km/week. Broadband ultrasonic attenuation was determined at baseline and after 1 year. Analysis of variance showed that values were increased (P less than 0.05) for the walkers relative to controls [walkers 103.3 (4.9) versus 116.1 (3.8) dB/MHz; controls 103.6 (5.5) versus 99.6 (5.4) dB/MHz]. We conclude that, in formerly sedentary women, a modest program of a widely acceptable form of exercise, brisk walking, can provoke an increase in this sensitive index of bone condition. PMID- 1913290 TI - Ultrasonic velocity as a predictor of strength in bovine cancellous bone. AB - Ultrasonic methods measure properties intrinsic to bone's structure that are not necessarily dependent on bone mass. Therefore, ultrasound may prove to be a useful tool for diagnosing bone fragility and osteoporosis. The goal of this study was to determine the relationship between apparent velocity of ultrasound (AVU) measured using the OsteoTechnology prototype I machine and cancellous bone yield strength (sigma y). AVU correlated well with sigma y (r = 0.753). Consistent with theory, the best predictor of cancellous bone strength was the combination of apparent density (rho a) and AVU, rho a (AVU)2, which had an r2 of 77.4%. PMID- 1913291 TI - Dexamethasone-treated ROS 17/2.8 rat osteosarcoma cells are responsive to human carboxylterminal parathyroid hormone peptide hPTH (53-84): stimulation of alkaline phosphatase. AB - We tested the effects of various parathyroid hormone (PTH) peptides on alkaline phosphatase (ALP) activity in the osteoblastic cell line ROS 17/2.8. In dexamethasone-treated ROS 17/2.8 cells there was a dose-related increase in ALP activity due to treatment with hPTH (53-84). ALP activity was stimulated by 10 nM hPTH (53-84) by a mean of 1.51 +/- 0.07-fold (P less than 0.001) in nine experiments, whereas the same dose of bPTH (1-34) and bPTH (1-84) inhibited enzyme activity to 0.36 +/- 0.02-fold (P less than 0.001) and 0.37 +/- 0.03-fold (P less than 0.001), respectively. Significant stimulation of ALP activity occurred with doses of hPTH (53-84) as low as 0.01 nM. There was no stimulation of enzyme activity by hPTH (53-84) in the absence of dexamethasone; the maximum ALP response to hPTH (53-84) occurred between 96 and 144 hours, and no significant effect was seen at time periods less than 96 hours. The optimum dose of dexamethasone required to enable the response to hPTH (53-84) was 10 nM. Carboxylterminal PTH fragments had a specific stimulatory effect on ALP activity in dexamethasone-treated ROS 17/2.8 cells, but the aminoterminal PTH effect appeared to be dominant, as the equimolar combination of bPTH (1-34) and hPTH (53 84) resulted in inhibition of ALP activity. Thus, in order for the effects of carboxylterminal fragments to be manifest, the cells would have to be stimulated under conditions in which the aminoterminal receptor is unoccupied; this could occur under some in vivo conditions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1913292 TI - Estrogen target cells during the early stage of medullary bone osteogenesis: immunohistochemical detection of estrogen receptors in osteogenic cells of estrogen-treated male Japanese quail. AB - The localization of estrogen receptors (ER) in osteogenic cells during the early stage of medullary bone osteogenesis was studied immunohistochemically in the femurs of estrogen-treated male Japanese quail. Alkaline phosphatase (ALP) activity was used as a marker for osteogenic cells. ER immunostaining was observed in the nuclei of weak ALP-positive bone lining cells on the endosteal bone surface of nontreated birds. After 24 hours of estrogen treatment, nuclear immunostaining was detected in ALP-positive preosteoblasts on the endosteal bone surface. After 48 hours, the medullary bone appeared to some degree along the endosteal surface. ER immunostaining was observed in the nuclei of ALP-positive osteoblasts on the medullary bone surface. This study demonstrates that ER are present in osteogenic cells, and suggests that estrogen directly acts on medullary bone osteogenesis. PMID- 1913293 TI - Is there an effective treatment for glucocorticoid-induced osteoporosis? PMID- 1913294 TI - Serum markers of bone formation in parenteral nutrition patients. PMID- 1913295 TI - Relationship among aluminum, osteoporosis, and Alzheimer's disease. PMID- 1913296 TI - Pitfalls in pit measurement. PMID- 1913297 TI - Prevention of corticosteroid-induced osteoporosis with salmon calcitonin in sarcoid patients. AB - The aim of this study was to evaluate the usefulness of salmon calcitonin (sCT) in preventing corticosteroid-induced osteoporosis. Three groups of patients with sarcoidosis requiring long-term steroid therapy were followed for 2 years with yearly evaluations of vertebral cancellous mineral content (VCMC) by quantitative computed tomography. The first group (n = 18) was treated with intramuscular (i.m.) sCT for the 2-year study period; the second (n = 11) with i.m. sCT for the first 4 months and then with sCT nasal spray for 20 months; the third (n = 35) received no sCT. We observed a large mineral loss in the third group but a very slight drop of VCMC in the two groups receiving sCT. SCT nasal spray was better tolerated and as effective as i.m. injections. The action of sCT appeared extremely useful, especially in the first year of steroid therapy when corticosteroid-induced mineral loss was maximal. We conclude that sCT nasal spray is a good tool for preventing corticosteroid-induced osteoporosis. PMID- 1913299 TI - The predictive value of bone loss for fragility fractures in women: a longitudinal study over 15 years. AB - Fifteen years after their forearm bone mineral content was measured, 366 women were measured again with the same single photon technique. 96 of the women had sustained one or more fragility fractures during that period. The initial bone mineral content was less in those women who were to have fractures. The rate of loss over the years did not differ between fracture and non-fracture women--the initial bone mass was the better predictor. Peak bone mass in the women in this study occurred before the age of 40. PMID- 1913298 TI - Skeletal size and bone mineral content in Turner's syndrome: relation to karyotype, estrogen treatment, physical fitness, and bone turnover. AB - Bone mineral content (BMC), bone mineral density, and metacarpal dimensions were studied in 50 women with Turner's syndrome aged 21-45 years in relation to karyotype, estrogen treatment, physical fitness, and biochemical markers of bone turnover. No differences were found between the 25 women with karyotype 45.X and women with other karyotypes. Forty-six women had received estrogen. Significant partial correlations were found between bone mineral density of the forearm and duration of estrogen treatment and physical fitness. BMC of the lumbar spine corrected for vertebral height (BMC(C)spine) was directly correlated with duration of estrogen treatment and height, marginally correlated with physical fitness, and inversely correlated with age. Outer metacarpal width was positively correlated with duration of estrogen treatment, age at initiation of therapy, and body weight. The diameter of medullary space showed negative correlation with physical fitness and height, and positive correlation with age at initiation of estrogen treatment. Cortical thickness was positively correlated with duration of estrogen treatment, physical fitness, and height. No convincing effects of estrogen could be demonstrated in women below the age of 30. Above the age of 30, all bone mineral measurements were markedly elevated in women treated for longer than the average of this age group. BMC(C)spine was inversely correlated with biochemical markers of bone formation. Our results demonstrate that estrogen treatment and physical fitness are important determinants of bone mineral status in Turner's syndrome and add to the evidence that estrogen treatment increases BMC in Turner's syndrome. PMID- 1913301 TI - Is dentistry programmed to self-destruct? PMID- 1913300 TI - Serum triiodothyronine, bone turnover, and bone mass changes in euthyroid pre- and postmenopausal women. AB - Hyperthyroidism and thyroid hormone substitutive therapy with serum iT3 in the normal range of values are known to lead to increased bone remodeling and loss of bone mass. We looked for a relationship between serum iT3 and bone metabolic or bone mass parameters in 402 euthyroid women aged 44-60. In a group of 93 premenopausal women, a group of 309 postmenopausal women, and a group of 118 untreated postmenopausal women, serum iT3 was higher in the women classified as having "high" bone turnover according to both alkaline phosphatases and hydroxyprolinuria values. In postmenopausal women, serum iT3 corrected for thyroid binding globulin (TBG) (T3c) was higher in those receiving no estrogen replacement therapy. In a longitudinal study (n = 131), the rate of changes in lumbar bone mineral content was associated with changes in T3c. A less favorable bone mass evolution was associated with an increase in serum T3c, and inversely. Data suggest that the relationship of iT3/bone metabolism is direct and not merely the consequence of estrogen induced changes in both iT3 and bone metabolism. iT3 should be explored at the bone cellular level as a possible mediator in bone metabolic changes occurring in menopause and many other clinical situations. PMID- 1913303 TI - Solving your scheduling woes. PMID- 1913302 TI - Meet the president--and his father. Interview by P. Ralph Crawford. PMID- 1913304 TI - Treatment of the ankylosed mandibular permanent first molar: a case study. AB - The treatment of ankylosed teeth has been reported. While the diagnosis of the condition can be readily made, the etiology remains unknown. Treatment of these teeth is aimed at preventing malocclusions and periodontal defects from developing. Once diagnosed, these teeth require careful evaluation and prompt treatment. Delaying treatment nearly always results in a less favorable outcome. In the case presented, it was thought best to attempt luxation rather than to extract the mandibular first molar to overcome the ankylosis. This reasoning was based on the fact that there was adequate space for the first molar to erupt into and the maxillary first molar had not over-erupted. Selection of the best mode of treatment will depend upon many factors, including space available for the eruption of the involved tooth, inclination of the tooth, stage of development of the dental arches and overall health of the involved tooth. PMID- 1913306 TI - The oral health status of older adults in four Ontario communities. PMID- 1913305 TI - The surgical management of maxillofacial pathology. PMID- 1913307 TI - [Concomitant and discriminatory validity of the Adolescents' Fear of Dental Treatment Cognitive Inventory]. AB - The revised edition of the Inventaire cognitif de la peur des traitements dentaire pour adolescent(e)s [Adolescents' Fear of Dental Treatment Cognitive Inventory] (ICPTD-A) was administered to 38 subjects chosen at random and to nine subjects chosen with an obvious dental phobia problem. Its concomitant validity was established by relating the ICPTD-A scores to those of a behavioral test. The Pearson correlation coefficients that were thus obtained were -0.66 for the general population and -0.87 for the population suffering from dental phobia. The discriminatory validity was then established with a repeated measurement variance analysis based on the scores of the dental phobics after the administration of a recognized psychological treatment program intended to reduce their phobia. The results have shown a statistically significant difference between the experimental and control groups as well as a significant difference between pre- and posttreatments. The authors have therefore concluded that the ICPTD-A is a valid tool for the assessment of dental phobia in 12-15-year-old adolescents. PMID- 1913308 TI - Localized fibrous pleural mesothelioma: CT findings. AB - The CT findings in 16 patients (20 examinations) with proven localized fibrous mesothelioma are described. These lesions proved to be large, uninvasive, sometimes heterogeneous, and enhancing solitary masses. These morphologic findings in an asymptomatic patient should be suggestive of this lesion. PMID- 1913309 TI - MRI features of spinal ganglioglioma. AB - Spinal cord ganglioglioma is a rare tumor most often encountered in the first three decades. Scanty computed tomography (CT) reports on the tumor describe it as a hypodense or cerebrospinal fluid (CSF) dense area with little contrast enhancement despite its solid nature. We report two cases of spinal ganglioglioma both involving almost the whole spinal cord. On magnetic resonance imaging (MRI), the tumors appear hypointense to the spinal cord on T1 and hyperintense to the cord on T2 images, and were mainly solid at exploration. It is important to recognize these tumors as long survival can be achieved after surgical resection. PMID- 1913310 TI - Benign non-parenchymal renal tumors: radiologic appearances. AB - Two non-parenchymal renal tumors, capsular leiomyoblastoma and schwannoma in renal sinus, are reported with respect to radiographic appearance, reviewing the literature. Computerized tomography (CT) scan and pyelography define the localization of the renal tumor substantiated by angiography identifying the feeding arteries. Precise investigation of neovascularity is necessary to exclude malignant potency. A tumor in the renal sinus without destruction of pelvo calyceal system should include schwannoma in the differential diagnosis. PMID- 1913311 TI - Abscessed splenic hydatid cyst: sonographic and CT findings. AB - Splenic hydatid cyst abscess formation is extremely rare. We present a surgically proved case of abscessed hydatid cyst of the spleen with its appearance on sonography and computed tomography (CT). Although both imaging methods do not confirm a diagnosis of abscessed splenic hydatidosis, they are valuable examinations to support the diagnosis and define the extent of disease. Percutaneous drainage of splenic abscessed lesions must be avoided when hydatid disease is suspected. PMID- 1913312 TI - Isolated rhombencephalosynapsis diagnosed by magnetic resonance imaging. AB - A case of human rhombencephalosynapsis diagnosed in vivo by magnetic resonance imaging (MRI) is presented that demonstrates fusion of the dentate nuclei and agenesis of the cerebellar vermis. To our knowledge, this condition in its isolated form has been previously diagnosed only at necropsy. The developmental features of the cerebellum are discussed and correlation with cerebellar function is also presented. Recognition of this anomaly in the living patient may be useful in further understanding the clinical significance of segmentation of the rhombencephalon. PMID- 1913313 TI - MRI of myositis ossificans circumscripta. AB - Myositis ossificans circumscripta (or pseudomalignant osseous tumor of soft tissue) may be confused with malignant neoplasms if there is no clear history of trauma. Two cases are presented in which magnetic resonance imaging (MRI) clearly demonstrates disproportionally extensive abnormal signal intensity along the course of muscle fibers. Although the specificity of this finding is uncertain, MRI enhances the level of confidence in diagnosing myositis ossificans. PMID- 1913314 TI - A 67-year-old man with a 1 1/2 year history of progressive left supraclavicular mass. PMID- 1913315 TI - Assessment of congenital hip dislocation with real-time ultrasound: a pictorial essay. AB - Real-time ultrasound (US) is the imaging method of choice for diagnosis and follow-up of congenital dislocation of the infant hip (CDH). Clinical aspects and the role of imaging are reviewed. Technique and anatomy, both normal and abnormal, are illustrated, as well as, the use of sonography during treatment with Pavlik harness and spica cast. Correlation of ultrasound findings with clinical examination, other available imaging studies and long-term patient follow-up shows 100% sensitivity and 100% specificity for real-time US diagnosis of CDH. PMID- 1913316 TI - Mesenteric ischemia: angiographic diagnosis and intervention. PMID- 1913317 TI - CT-guided liver biopsy: an update. AB - Computed tomography (CT)-guided liver biopsy has become an accepted part of the diagnostic evaluation of patients with benign and malignant hepatic disease The advantages of imaging guidance over blind percutaneous biopsy are now well established in the literature. Controversy continues to exist, however, over the safety and accuracy of the procedure, as well as over the proper choice of needle: large-caliber cutting needle versus small caliber aspiration needle. In 1984, our group reported the results in a preliminary set of 180 patients in whom CT-guided biopsy of focal liver lesions was performed. The study indicated that cutting-needle sampling could provide increased diagnostic accuracy over fine needle aspiration in both benign and malignant hepatic disease without a significant increase in complications. This paper reports the results in a series of 179 new patients who underwent CT-guided liver biopsy using a variety of needles. Comparison is again made between fine-needle and cutting-needle biopsy with respect to diagnostic accuracy and safety. A detailed discussion of the proper choice of biopsy needle as well as of the causes of both biopsy failure and complications is provided. PMID- 1913318 TI - The 1990 Merck Frosst Award. Ischemic and reperfusion injury in the heart. Cellular mechanisms and pharmacological interventions. AB - Reperfusion in the heart represents an important form of tissue injury, particularly in view of the emerging importance of reperfusion protocols aimed at salvaging the ischemic myocardium. Both the manifestations and the causes of reperfusion injury are multifold. With respect to the former, reperfusion injury can be characterized by various abnormalities including development of arrhythmias, contractile dysfunction, ultrastructural damage as well as various defects in intracellular biochemical homeostasis. The mechanisms underlying myocardial reperfusion injury are equally complex, but most likely involve numerous processes acting in concert resulting in eventual cell death. In this review, a description of various such potential mechanisms, which represent primary interests of the author, are presented. An understanding of these mechanisms has led to novel pharmacological approaches towards the protection of the reperfused myocardium. For instance, several lines of evidence implicate enhanced eicosanoid, and in particular prostaglandin, synthesis in reperfusion injury, since (1) such injury is involved with enhanced prostaglandin biosynthesis, (2) inhibition of prostaglandin synthesis with various nonsteroidal anti-inflammatory drugs attenuates injury, and (3) exogenous prostaglandins increase injury. Another intracellular process that is emerging as an important contributor to reperfusion injury in the heart is the Na+/H+ exchanger, which is most likely activated upon reperfusion. Such activation would lead to numerous intracellular disturbances including the increased synthesis of prostaglandins and elevated intracellular Ca2+ concentrations. Indeed, inhibitors of Na+/H+ exchange such as amiloride have been shown to effectively inhibit reperfusion injury. Reperfusion is also associated with depressed mitochondrial function, particularly in subsarcolemmal mitochondria which are rapidly injured as a result of both ischemic and reperfusion conditions. Preservation of mitochondrial function with dissimilar approaches such as carnitine or phosphatidylcholine administration markedly reduces reperfusion injury-. A nonpharmacological novel approach towards the protection of the reperfused myocardium represents the induction of so-called stress or heart shock proteins in the heart prior to initiation of ischemia and reperfusion. The salutary effect of the heat shock response may be dependent not on the heat shock proteins themselves, but through the concomitant elevation of tissue catalase content resulting in enhanced detoxification of intracellular hydrogen peroxide. Thus reperfusion injury represents numerous complex events such that manipulations aimed at limiting such injury can be initiated to prevent specific defects with the ultimate goal of an overall reduction in cell damage. PMID- 1913319 TI - Effects of postnatal growth and denervation on characteristics of the saphenous artery in SHR and WKY rats between 3 and 6 weeks of age: an in vitro study. AB - Thigh vessels of spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats were unilaterally surgically denervated at 10 days of age by femoral nerve section. Denervated and contralateral control segments of saphenous arteries from 3- and 6-week-old rats were mounted in a small vessel myograph for study. Both strains showed growth changes in blood pressure, but there was no significant difference between WKY and SHR. Both strains also had significant growth changes in vessel dimensions and the in vitro measurements suggested that SHR vessels had a thicker wall. Denervation did not affect vessel size. Transmural nerve stimulation indicated loss of innervation due to the surgical procedure. In the denervated vessels, both norepinephrine (NE) and 5-hydroxytryptamine (5-HT) dose response curves were shifted to the left, indicating a postjunctional increase in sensitivity. Maximum tension developed was in the order K+ greater than 5-HT greater than NE. In comparing the two strains, vessels from 6-week-old SHR were less sensitive to 5-HT. Relaxation to acetylcholine was significantly decreased in denervated arteries from WKY, whereas in SHR the significant decrease occurred only at 3 weeks. Denervated vessels from both rat strains at 3 weeks showed greater relaxation to beta-receptor activation, but not at 6 weeks of age. Therefore, the absence of functional innervation resulted in altered function of the saphenous artery wall. PMID- 1913321 TI - Restoration of lipoprotein lipase activity in insulin-deficient rats by insulin infusion is tissue-specific. AB - The activity of lipoprotein lipase was measured in white and brown adipose tissues, red vastus lateralis muscle, and heart of rats that have been insulin deficient (streptozotocin, 75 mg.kg-1) for 2 weeks, and that have then received implants of insulin-delivering minipumps (17 U.kg-1.day-1) for 1 or 4 days. Normal glycemia was restored in insulin-deficient animals after 4 days of insulin treatment. Hypertriglyceridemia, but not hypercholesterolemia, was reversed after 4 days of insulin infusion. After 2 weeks of insulin deficiency, fasting lipoprotein lipase activity was lowered in all tissues studied. In white adipose tissue, lipoprotein lipase decreased to 50% of control values. After a single day of insulin infusion, even if tissue weight has not yet been greatly affected, total activity was completely restored to control levels. Enzyme activity in brown adipose tissue was also depressed in deficient animals, and insulin infusion was followed by a slow recovery of activity, to a level intermediate between those of control and insulin-deficient groups. Insulin status had milder effects on lipoprotein lipase activity in vastus lateralis muscle than in the adipose tissues. Deficient rats displayed 60% less activity than controls, and 4 days of hormone infusion only partially restored enzyme activity. There was a large loss of lipoprotein lipase in the heart following 2 weeks of insulin depletion, which was not counteracted by hormone infusion. Thus the speed and extent of recovery of lipoprotein lipase activity following hormone replacement in insulin-deficient animals varied widely among tissues. These findings suggest that insulin is part of the factors that determine the tissue specificity of lipoprotein lipase regulation. PMID- 1913320 TI - Voltage-dependent inactivation of the potassium current of embryonic chick hepatocytes. AB - The whole-cell patch electrode voltage clamp technique was used to study the inactivation properties of the delayed rectifying potassium current of single cultured embryonic chick hepatocytes at 20 degrees C. The potassium current activates maximally within 250-500 ms of membrane depolarization, after which it decays with a monoexponential time course. Both steady-state activation and inactivation are voltage dependent. Steady-state inactivation declines from 100% at -5 mV to 0 near -70 mV. with half inactivation at -41 mV. At the resting potential (EM) of these cells (-21.5 +/- 6.0 mV, n = 36) 6-18% of the IK channels are not inactivated and less than 5% are open. Development and removal of inactivation follow single exponential time courses. The inactivation time constant attains a maximum of around 30 s at -35 mV and is sharply voltage dependent at the EM of these cells. Measurement of EM under current clamp shows random oscillations of 5-10 mV amplitude. We suggest that the voltage- and time dependent properties of IK, in tandem with a time- and voltage-independent, non selective current also seen here, would provide the mechanism for a fluctuating EM. PMID- 1913322 TI - Effects of isoflurane, halothane, and enflurane on myocardial flow and energy stores in the perfused rat heart. AB - The effect of three volatile anesthetics (halothane, enflurane, and isoflurane) on coronary flow and metabolic state of isolated rat hearts was studied. These anesthetics are coronary dilators and their effects are dose dependent. At 2 MAC (minimum alveolar concentration), isoflurane, enflurane, and halothane increase coronary flow by 114 +/- 5.9, 93 +/- 6.1, and 77 +/- 6.4%, respectively (p less than 0.001). At these concentrations, they also have a modest but significant metabolic effect causing a 30% reduction in myocardial ATP and phosphocreatine levels, with no significant modification in ADP and AMP concentrations. Energy charge and lactate/pyruvate ratio were also unaffected by these anesthetics. The vascular and metabolic effects were reversible within 2 and 30 min, respectively. Perfusion of the hearts with a Krebs-Henseleit solution without Pi did not interfere with the vascular and the metabolic effect of the anesthetics; however, in this case, ATP and phosphocreatine concentration did not return to control levels after their discontinuation despite full recovery of the vascular effect. These data suggest that the volatile anesthetics have direct coronary vascular and myocardial metabolic effects and that these effects occur independently. PMID- 1913323 TI - The effect of isoproterenol on fluid and electrolyte transport in the inner medullary collecting duct. AB - In the late distal and cortical collecting tubule, which is the principal regulatory site for potassium (K) excretion, vasopressin stimulates, and epinephrine via beta-adrenergic action, inhibits K secretion. In the inner medullary collecting duct (IMCD) we have shown that vasopressin also stimulates K secretion. The present experiments were designed to determine whether the beta adrenergic agonist, isoproterenol, would induce K reabsorption in the IMCD, and (or) prevent a secretory response to acute KCl infusion. Two groups of rats, with or without isoproterenol administration (3 micrograms/h), were subjected to retrograde microcatheterization of the IMCD before and during infusion of 0.83 mol/h KCl. Isoproterenol reduced plasma K concentration and urinary K excretion, but the response to acute KCl infusion was qualitatively similar to control. Isoproterenol decreased delivery of potassium, chloride, and fluid to the IMCD, there was no net transport of K along the duct in either group, and KCl infusion did not result in K secretion in either group. The results indicate that isoproterenol may inhibit K secretion in the late distal or cortical collecting tubule. However, there was no statistically significant difference in K transport along the IMCD between isoproterenol and control groups. Reduced sodium excretion, which was found during isoproterenol administration both before and after KCl infusion, was associated with no change in sodium delivery but with increased sodium reabsorption in the IMCD. This increased sodium reabsorption may be a direct effect of isoproterenol, or may be due to reflex cardiovascular adjustments associated with systemic actions of the drug. PMID- 1913324 TI - Impairment of iodothyronine 5'-deiodinase activity in brown adipose tissue and its acute stimulation by cold in selenium deficiency. AB - The activity of the type II iodothyronine 5'-deiodinase enzyme in brown adipose tissue has been examined in rats-fed a selenium-deficient diet. Iodothyronine 5' deiodinase activity was threefold lower in brown adipose tissue of deficient rats than in control animals. The activity of glutathione peroxidase, a biochemical index of selenium deficiency, was also greatly decreased in deficient animals. Cytochrome oxidase activity in brown fat was, however, unaltered by selenium deficiency. Acute exposure to cold (4 degrees C for 18 h) resulted in a substantial increase in iodothyronine 5'-deiodinase activity in brown adipose tissue of control rats, but the stimulatory effect of cold was attenuated in selenium-deficient animals. These results support the concept that the iodothyronine 5'-deiodinases are selenium-dependent enzymes, and indicate that the thermogenic response to cold may be impaired in selenium deficiency. PMID- 1913325 TI - Inhibition of the acetylcholine-induced relaxation of canine isolated basilar artery by potassium-conductance blockers. AB - Canine basilar artery rings precontracted with 5-hydroxytryptamine (0.1-0.5 microM) relaxed in the presence of acetylcholine (25-100 microM), sodium nitroprusside (0.1 microM), or stimulation of the electrogenic sodium pump by restoration of extracellular K+ (4.5 mM) after K(+)-deprivation. Acetylcholine induced relaxation is believed to be caused by the release of endothelium-derived relaxing factor (EDRF) and is prevented by mechanical removal of the endothelium, while relaxations induced by sodium nitroprusside or restarting of the sodium pump are endothelium-independent. Acetylcholine-induced relaxation was selectively blocked by pretreatment of the tissue with the nonselective K+ conductance inhibitors, 4-aminopyridine (4-AP, 3 mM), Ba2+ (1 mM), and tetraethylammonium (20 mM), 4-AP also blocked ACh-mediated relaxation in muscles contracted with elevated external K+. Relaxation of 5-hydroxytryptamine-induced contraction by sodium nitroprusside, or by addition of K+ to K(+)-deprived muscle, was not affected by 4-AP. Relaxation of basilar artery with acidified sodium nitrite solution (containing nitric oxide) was reduced by 4-AP. These results suggest that 4-AP and possibly Ba2+ inhibit acetylcholine-induced endothelium-dependent relaxation by inhibition of the action of EDRF on the smooth muscle rather than through inhibition of release of EDRF. The increase in K+ conductance involved in acetylcholine-induced relaxation is not due to ATP inhibited K+ channels, as it is not blocked by glyburide (10(-6) M). Endothelium derived relaxant factor(s) may relax smooth muscle by mode(s) of action different from that of sodium nitroprusside or by hyperpolarization due to the electrogenic sodium pumping.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1913326 TI - Calcium dependence of effects of endothelin on rat mesenteric microvessels. AB - We investigated the calcium dependence of the effects of endothelin (ET) on resistance vessels (less than 300 microns lumen diameter) from the mesenteric vascular bed of the rat, mounted on a wire myograph. ET-1 induced a potent sustained contraction with an ED50 of 12 nmol/L. The response to ET-3 and big ET at the maximum concentrations used (100 nmol/L) was less than 40% of that to ET 1, with an estimated ED50 of 45 nmol/L. Relaxation of the ET-1-induced contraction was slow, and resulted in a reduction of the maximum response to a second challenge with ET-1 to 60% of the initial contraction after 3 h. Long lasting tachyphylaxis to arginine vasopressin (AVP) induced contraction also occurred. The response to 100 nmol/L ET-1 produced an active tension 88% greater than that induced by 124 mmol/L KCl, and similar to that produced by norepinephrine and AVP. The response to 100 nmol/L ET-1 in the absence of calcium + 1 mmol/L EGTA in the medium for 30 min resulted in a maximum contraction of 43% of the response in the presence of calcium, followed by a faster relaxation rate. The addition of calcium produced a further contraction, and stimulation with 100 nmol/L ET-1 at this point did not result in further response. The calcium channel blocker nitrendipine in concentrations of 1-10 mumol produced increasing reductions of the responses to 100 nmol/L ET-1 to 35% at the higher concentration. Nitrendipine (3 mumol/L) partially blocked the response to calcium after ET-1 was added in the absence of calcium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1913328 TI - Effects of retinoic acid on the concentrations of radioactive metabolites of retinol in tissues of rats maintained on a retinol-deficient diet. AB - The effects of feeding retinoic acid for 2 and 6 days on the metabolism of labeled retinol in tissues of rats maintained on a vitamin A deficient diet was studied. The metabolites of retinol were analyzed by high performance liquid chromatography. Feeding retinoic acid for 2 days significantly reduced the blood retinol and retinyl ester levels without affecting the vitamin A content of the liver. In intestine and testis the content of labeled retinoic acid was decreased significantly by dietary retinoic acid. Addition of retinoic acid to the diet for 6 days resulted, in addition to decreased blood retinol and retinyl ester values, in an increase in the retinyl ester values in the liver. The accumulation of retinyl ester in the retinoic acid fed rat liver was accompanied by an absence of labeled retinoic acid. Kidney tissue was found to contain the highest levels of labeled retinoic acid, retinol, and retinyl esters; dietary retinoic acid did not alter the concentrations of these retinoids in the kidney during the experimental period. Since kidney retained more vitamin A when the liver vitamin A was low and also dietary retinoic acid did not affect the concentrations of radioactive retinoic acid in the kidney, it is suggested that the kidney may play a major role in the production of retinoic acid from retinol in the body. PMID- 1913327 TI - Relationship between myocardial amiodarone concentration and antiarrhythmic effect in dogs with myocardial infarction and electrically induced ventricular arrhythmias. AB - The relationship between the antiarrhythmic effect of amiodarone and its myocardial concentration was studied in dogs with 1-week-old myocardial infarction and reproducibly inducible sustained ventricular tachycardia or ventricular fibrillation. Three groups of animals (n = 10/group) received amiodarone, 40 mg.kg-1.day-1 (low-dose amiodarone), amiodarone 60 mg.kg-1.day-1 (high-dose amiodarone), or no amiodarone (control group). After 1 week of treatment, programmed electrical stimulation was repeated, and plasma and myocardial amiodarone and desethylamiodarone concentrations were measured. In the control group, sustained ventricular tachycardia or ventricular fibrillation was induced in six dogs (p = NS) when compared with baseline data. In the low-dose amiodarone group, sustained ventricular tachycardia or ventricular fibrillation was induced only in two dogs after 1 week of treatment (p less than 0.01 vs. baseline data). Sustained ventricular tachycardia or ventricular fibrillation was induced in seven dogs after treatment with high-dose amiodarone (p = NS vs. baseline data). Plasma amiodarone concentration in the low-dose amiodarone group (2.54 +/- 1.95 micrograms/mL) was significantly less (p less than 0.01) than that in the high-dose amiodarone group (4.64 +/- 1.66 micrograms/mL). Similarly, the plasma desethylamiodarone in the low-dose amiodarone group (0.32 +/- 0.16 microgram/mL) was significantly less (p less than 0.001) than that in the high amiodarone dose group (0.56 +/- 0.23 microgram/mL). The myocardial amiodarone concentration in the low-dose amiodarone group (49.7 +/- 23.1 micrograms/g) was significantly lower (p less than 0.001) than that in the high-dose group (98.4 +/ 32.1 micrograms/g).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1913329 TI - Effect of systemic inhibition of prostaglandin synthesis on muscle protein balance after trauma in the rat. AB - Anaesthetized rats were subjected to a single impact trauma to the medial aspect of the right hindlimb (gastrocnemius muscle), and were compared with sham-treated controls. For 3 days after injury, muscles of the traumatized limb showed a marked catabolic response. Muscle protein repletion commenced after day 3, however, this process was not complete until 21 days after injury. Muscles of the uninjured limb of the traumatized rats also showed a distinct catabolic response, compared with rats that were never injured, although this response was less in magnitude than that of the injured limb. At 3 days after trauma, augmented synthesis of prostaglandin (PG)E2 by muscles of the injured and uninjured limb provided evidence of a local and systemic inflammatory response. Inhibition of PG synthesis by the systemic administration of naproxen (6-methoxy-alpha-methyl-2 napthaleneacetic acid) significantly reduced the catabolic loss of muscle protein seen locally and peripherally to the injury site. PMID- 1913330 TI - Resistance of hepatic glycogen to depletion in obese Zucker rats. AB - Glycogen stores (liver and carcass) have been studied in lean and obese Zucker rats. The animals were submitted to one of three feeding conditions: ad libitum, a 48-h fast, or a 48-h fast and food ad libitum for 24 h, and to two environmental conditions, either thermoneutrality or an acute cold exposure (2 days at 4-7 degrees C). After a 2-day fast at 25 degrees C, the liver glycogen store was reduced by 45 times in the lean rats, while it was decreased by only 3 times in the obese rats. Under these conditions, the liver glycogen store was 45 times higher in the obese than in the lean rats. After 2 days in the cold, liver glycogen store was 4.4 times higher in obese rats than in lean rats. After a 2 day fast in the cold, the liver glycogen store in the obese rats was 30 times higher than in the lean rats. In comparison to fasting at thermoneutrality, fasting in the cold did not lead to a further reduction in hepatic glycogen in obese Zucker rats. The differences observed in the mobilization of the hepatic glycogen store between obese and lean rats have not been found in the mobilization of the carcass glycogen store. Drastic conditions, such as a 2-day fast in the cold, did not exhaust the glycogen store in obese Zucker rats. The present observations point out that obese Zucker rats cannot mobilize the entire hepatic glycogen store, as seen in lean control rats. The role of this abnormality in the high hyperlipogenesis that maintains the obese state is still to be evaluated. PMID- 1913331 TI - Creatine kinase and mechanical and mitochondrial functions in hereditary and diabetic cardiomyopathies. AB - To determine whether the development of cardiomyopathies is associated with alterations in creatine kinase function, the functional properties of cardiac contractile apparatus and mitochondria were studied in two different models of cardiomyopathies, the Syrian hamster (hereditary dilated cardiomyopathy, strain UM-X7.1, 200 days old) and the diabetic rat (4-6 weeks after injection of streptozotocin) using ventricular skinned fibers. After Triton X-100 treatment, the hereditary cardiomyopathic fibers demonstrated decreased maximal calcium activated tension and unchanged calcium sensitivity, whereas fibers from diabetic hearts exhibited unchanged maximal tension and increased calcium sensitivity, when compared with their respective controls. In both cases myofibrillar creatine kinase appeared unchanged. The functional properties of total tissue mitochondria were evaluated using saponin-skinned fibers. Coupling between oxidation and phosphorylation was not altered in cardiomyopathies. Respiration rate (per unit of tissue dry weight) was normal in hereditary cardiomyopathy but was considerably lower in diabetic fibers compared with control fibers. In both models of cardiomyopathies, creatine-stimulated respiration was significantly lower than in controls, thus indicating the depression of functional activity of mitochondrial creatine kinase. PMID- 1913332 TI - Amiodarone antagonizes the effects of T3 at the receptor level: an additional mechanism for its in vivo hypothyroid-like effects. AB - Amiodarone is a diiodinated benzofuran derivative that has some structural similarities to the thyroid hormones and contains two iodine atoms per molecule. It has exhibited hypothyroid-like effects that are thought to be the result of an inhibition of thyroid hormone synthesis due to iodine load, a decrease in the T4 to T3 conversion, and (or) a competitive binding for T3 receptors. The aim of this study was to determine if this third mechanism contributes to the hypothyroid-like effects of amiodarone in vivo. To do so, some characteristic features known to be influenced by hypothyroidism were determined in surgically thyroidectomized rats (n = 48), which received replacement doses of T3 (0.5 and 1.0 microgram.100 g-1.day-1) with or without amiodarone (60 mg.kg-1.day-1). Thyroidectomy produced a hypothyroid state upon which amiodarone had no detectable effects except a negative body weight gain. T3 (0.5 microgram) nearly normalized the thyroid status of the animals, but the concomitant administration of amiodarone induced hypothyroid-like effects suggesting that these effects are dependent on T3. Higher doses of T3 (1.0 microgram) produced hyperthyroid-like effects and attenuated the effects of amiodarone. Unexpectedly, amiodarone decreased T3 plasma concentrations. To determine if the effects of amiodarone were the results of a decrease in T3 plasma and myocardial concentrations or a competition with T3 for its receptors, exogenous T3 pharmacokinetics were studied in thyroidectomized rats receiving T3 (0.5 microgram) with or without amiodarone. The results suggested that amiodarone increased T3 cardiac concentrations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1913333 TI - Muscarinic-receptor functioning in tracheas from normal and ovalbumin-sensitive guinea pigs. AB - Responses to bilateral vagal nerve stimulation, to field stimulation, and to exogenous methacholine and histamine were compared in tracheas isolated from (a) saline injected (i.p.) and saline-aerosol exposed guinea pigs (control), (b) ovalbumin-sensitized and saline-aerosol exposed (sensitized) guinea pigs, and (c) ovalbumin-sensitized and 2% ovalbumin-aerosol exposed (challenged) guinea pigs. Tracheal pressor responses (cmH2O; 1 cmH2O = 98.1 Pa) to nerve and field stimulation, and maximal responses to methacholine and histamine were significantly increased in animals from group c compared with groups a and b. Dose-response lines in response to the two agonists, expressed as percent maximal contraction, did not differ among the groups. The M1 antagonist pirenzepine (0.1 10 nM) selectively reduced responses to nerve stimulation in all three groups. The M2 antagonist gallamine potentiated responses to nerve or field stimulation in all three groups. We conclude that M1, M2, and M3 muscarinic receptor functioning is similar in control and ovalbumin-sensitized guinea pigs. Changes in post-receptor transduction mechanisms may mediate the increased responsiveness noted in animals from group c. PMID- 1913334 TI - Diabetes-induced rat hyposensitivity to compound 48/80. AB - Rat mortality and contractile responses of isolated tracheas to compound 48/80 from rats made diabetic 4 days before by a single intravenous injection of alloxan and from diabetic rats that had been treated with insulin 6 h before were compared with control animals. Diabetic animals and tracheal segments from diabetic rats were significantly less responsive to compound 48/80 than control and insulin-treated diabetic animals. On the other hand, diabetic animals have a lower quantity of peritoneal mast cells than control rats, and insulin restored the normal quantity of cells in diabetic animals. These data indicate that diabetes elicits an hyposensitivity to compound 48/80, possibly related to a diabetes-induced decrease in the mast cell count. PMID- 1913335 TI - Interaction of glyceryl trinitrate and sodium nitroprusside with bovine pulmonary vein homogenate and 10,000 x g supernatant: biotransformation and nitric oxide formation. AB - The current proposed mechanism of action of nitrovasodilator drugs involves biotransformation to nitric oxide, which is postulated to be the active vasodilator substance. Our objective was to determine whether nitric oxide was formed from two prototype nitrovasodilator drugs, glyceryl trinitrate (GTN) and sodium nitroprusside (SNP), after incubation with bovine pulmonary vein (BPV) preparations. GTN or SNP was incubated in an argon atmosphere with phosphate buffer, BPV homogenate, or the 10,000 x g supernatant fraction of the homogenate. Nitric oxide formation, as determined by a chemiluminescence-headspace gas method, was measurable following the incubation of SNP with BPV homogenate and 10,000 x g supernatant. There was no detectable formation of nitric oxide from the incubation of GTN with the two BPV preparations, although GTN was biotransformed to glyceryl dinitrate, as determined by gas-liquid chromatography. There was decreased recovery of nitric oxide during the incubation of authentic nitric oxide with the two BPV preparations as compared with buffer. In conclusion, formation of nitric oxide was measured for the interaction of SNP, but not GTN, with BPV preparations. However, the data do not exclude the possible formation of nitric oxide from GTN, as nitric oxide was shown to be sequestered or transformed by the BPV preparations. PMID- 1913336 TI - Growth of Listeria monocytogenes in murine macrophages and its modulation by cytokines; activation of bactericidal activity by interleukin-4 and interleukin 6. AB - Bone marrow derived macrophages were infected with a virulent strain of Listeria monocytogenes, and the ability of selected cytokines to modify the intracellular growth was assessed. Macrophage monolayers pretreated with either interferon gamma or tumour necrosis factor were shown to exert a significant listericidal activity. Treatment of monolayers with granulocyte-macrophage colony stimulating factor led to no significant difference in the ability of Listeria to invade and multiply within these cells. Moreover, pulsing of macrophage monolayers with interleukin-6 (IL-6) led to a slight enhancement of Listeria growth in the macrophages, whereas interleukin-4 (IL-4) did not modify Listeria growth. In other sets of experiments, macrophage monolayers were treated with cytokines after phagocytosis of the bacteria. In these conditions, interferon-gamma endowed macrophages with only a modest ability to kill Listeria. Conversely, treatment of monolayers with IL-6 or IL-4 at the time of infection led to expression of high bactericidal activity. Collectively, these results suggest that macrophages may respond to different signals, which enhance their antimicrobial activity before or after infection. Furthermore, B-cell stimulatory factors (IL-4 and IL-6) are potent macrophage-activating molecules. PMID- 1913337 TI - p-Hydroxybenzoylformic acid and (R)-(-)-p-hydroxymandelic acid, two antifungal compounds isolated from the liquid culture of the ectomycorrhizal fungus Pisolithus arhizus. AB - Two antifungal compounds isolated from the liquid culture medium of Pisolithus arhizus were identified as p-hydroxybenzoylformic acid and (R)-(-)-p hydroxymandelic acid and given the trivial names pisolithin A and pisolithin B, respectively. The efficacy of the compounds to inhibit the germination of conidia of Truncatella hartigii was compared with that of commercially available structural analogues, and a comparable range of effectiveness for 50% germination inhibition (GI50) of conidia was recorded. The commercially available synthetic compounds (R)-mandelic acid, benzoylformic acid, and racemic p-hydroxymandelic acid, had GI50 values of 82, 72, and 59 micrograms/mL, respectively, as compared with the natural compounds pisolithin A, 67 micrograms/mL, and pisolithin B, 71 micrograms/mL. Two synthetic S enantiomers of mandelic acid, (S)-mandelic acid and (S)-(+)-p-hydroxymandelic acid, were the most effective compounds, with GI50 values of 31 and 33 micrograms/mL, respectively. A sodium salt of mandelic acid had no activity below 500 micrograms/mL. Pisolithin A and pisolithin B were compared with polyoxin D for inhibition of hyphal growth, as measured by protein estimation. Both pisolithin A and B measured higher levels of putative extractable protein than polyoxin D, but less mycelial wet weight was measured. It is suggested that the pisolithins caused a disruption of cell turgor. A measurement of mycelial dry weights of phytopathogens, incubated with the commercially available analogues, benzoylformic acid and racemic p hydroxymandelic acid, indicated that benzoylformic acid was either more effective than, or as effective as, racemic p-hydroxymandelic acid or nystatin in arresting fungal growth.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1913338 TI - X-ray inactivation, Weigle reactivation, and Weigle mutagenesis of the lysogenic Vibrio kappa phage. AB - Vibrio cholerae lysogenic kappa phage was inactivated by X-ray (60 kV) in a dose dependent manner, the inactivation dose leading to 37% survival (D37) in phosphate-buffered saline (PBS), pH 7.4, being 0.36 kGy. The phages were significantly protected against X-ray irradiation when histidine or cysteine or both were present in PBS or when phages were irradiated in nutrient broth. Maximum protection was offered when both histidine (10.0 mM) and cysteine (10.0 mM) were present in PBS (dose enhancement factor being 4.17). The X-irradiated kappa phages also underwent a small but significant Weigle reactivation and also Weigle mutagenesis in the UV-irradiated V. cholerae host H218Smr. The Weigle factor or the frequency of clear-plaque mutants increased with increasing UV dose, attained a maximum at a UV dose of 2.4 J m-2, and thereafter decreased gradually with a further increase of the UV dose. The X-ray dose (D)--survival (S) curves could be empirically described by the equation S = exp[-(aD + bD2)], where a and b are constants depending on the irradiation conditions, and a good agreement between the theoretical curves and experimental data was obtained. PMID- 1913339 TI - Influence of environmental conditions on infection of Klebsiella pneumoniae by two different types of bacteriophages. AB - The adsorption and efficiency of plating of bacteriophages FC3-1 and FC3-9 on Klebsiella pneumoniae C3 (serotype O1:K66) cells grown at different pHs and temperatures were quantitated. Bacteriophage FC3-1, with lipopolysaccharide as its bacterial receptor, showed a large decrease in efficiency of plating on bacteria grown at low pH or low temperature. Under the same conditions, no significant decrease in efficiency of plating was found for bacteriophage FC3-9, a phage requiring capsule and lipopolysaccharide for its adsorption and carrying capsule-depolymerizing activity. We demonstrate that K. pneumoniae C3 cells grown at low pH or low temperature have less lipopolysaccharide exposed on their surface. We conclude that this is why lipopolysaccharide-specific phage FC3-1 less efficiently infects bacterial cells grown under those conditions. We propose that bacteriophage FC3-9 efficiently infects bacterial cells grown at low pH or low temperature because its enzymatic activity on the capsule makes lipopolysaccharide available to this phage. PMID- 1913340 TI - Biosynthesis of isochorismate in Klebsiella pneumoniae: origin of O-2. AB - The shikimate metabolites are key precursors to a large number of natural products, including aromatic amino acids. Chorismic acid is an important branch point in the biosynthetic pathway to aromatic amino acids. Chorismic acid is also unique among natural products since it is the only compound known to undergo an enzymatic Claisen rearrangement. A metabolite of chorismic acid, isochorismic acid, first observed in Aerobacter aerogenes differs in its chemical structure by the location of the hydroxyl group and the double bonds. Isochorismic acid is a precursor to a growing number of shikimate-derived metabolites. Isochorismic acid has also been postulated to be an intermediate of m-carboxyaromatic amino acids, implying another enzymatic Claisen rearrangement. In this publication, we have isolated isochorismate synthase and found that on lyophilization the enzyme is stable for at least 6 months at -20 degrees C. Incubation of chorismate with this preparation in water enriched with 18O led to incorporation of one atom of 18O as proven from the fast atom bombardment mass spectra of the HPLC purified derived isochorismate. PMID- 1913341 TI - Experimental lethal infection of Leptospira interrogans in mice treated with cyclophosphamide. AB - After preadministration of cyclophosphamide (300 mg/kg), BALB/c mice were lethally infected with Leptospira interrogans serovar lai and a virulent strain of Leptospira interrogans serovar copenhageni, and leptospiral cells were detected in both kidneys of infected mice by indirect immunofluorescent assay. Nonpathogenic leptospirae, Leptospira biflexa serovar patoc, Leptonema illini, and an avirulent strain of L. interrogans serovar copenhageni, were not parasitic to the mice treated with cyclophosphamide. The cyclophosphamide-treated mice were protected from the homologous leptospiral infection by passive immunization with anti-leptospiral monoclonal antibody or with rabbit antiserum and by active immunization with lyophilized organisms or with protective antigen. The results of active immunization in mice treated with cyclophosphamide agreed well with those in nontreated hamsters, which were sensitive to the organisms. Furthermore, these experiments were reproducible with any lot of cyclophosphamide used. These results indicated that cyclophosphamide-treated mice can be used in the experimental infection of Leptospira in place of hamsters or guinea pigs. PMID- 1913343 TI - Calcium binds to and is required for biological activity of the 104-kilodalton hemolysin produced by Actinobacillus pleuropneumoniae serotype 1. AB - Actinobacillus pleuropneumoniae serotype 1, strain Shope 4074, was grown on agar medium containing 10 mM Ca2+ and under Ca2+ limiting conditions by addition of 2 and 5 mM EGTA to the growth medium. Hemolysis of washed bovine erythrocytes was observed from the culture grown in Ca2+ excess but not from the two cultures where Ca2+ was chelated from the growth medium by using EGTA. However, the hemolytic activity of these latter two cultures could be restored if 10 mM Ca2+ was added to the dilution buffer. This restored hemolytic activity could be neutralized with a rabbit homologous polyclonal antiserum specific for the 104 kDa hemolysin of serotype 1 but not with preimmune serum from the same rabbit. Stained SDS-PAGE gels and immunoblots showed the 104-kDa protein hemolysin in fractions from each of the three growth conditions. Thus, the restored hemolytic activity was associated with the 104-kDa protein in the three cultures. In addition, the 104-kDa protein, when electroblotted onto nylon membranes, bound 45Ca, indicating that the molecule has binding sites for Ca2+. The results indicate that Ca2+ is required for the biological activity of the 104-kDa hemolysin of A. pleuropneumoniae serotype 1. PMID- 1913342 TI - Modulation of Clostridium difficile induced mortality as a function of the dose and the viability of the Saccharomyces boulardii used as a preventative agent in gnotobiotic mice. AB - The ability of viable and nonviable Saccharomyces boulardii to protect gnotobiotic mice from Clostridium difficile induced mortality was tested. With the exception of irradiated S. boulardii, which retained some activity, only viable yeast protected the mice from lethality. The survival of C. difficile infected mice was dependent on the dose of the yeast provided in the drinking water. PMID- 1913344 TI - Simultaneous degradation of acetonitrile and biphenyl by Pseudomonas aeruginosa. AB - A bacterium capable of utilizing either acetonitrile as the sole source of carbon and nitrogen or biphenyl as the sole source of carbon was isolated from soil and identified as Pseudomonas aeruginosa. The bacterium also utilized other nitriles, amides, and polychlorinated biphenyls (PCBs) as growth substrates. Acetonitrile- or biphenyl-grown cells oxidized these substrates without a lag. In studies with [14C]acetonitrile, nearly 74% of the carbon was recovered as 14CO2 and 8% was associated with the biomass. In studies with [14C]biphenyl, nearly 68% of the carbon was recovered as 14CO2 and nearly 6% was associated with the biomass. Although higher concentrations of acetonitrile as the sole sources of nitrogen inhibited the rates of [14C]biphenyl mineralization, lower concentrations (0.05%, w/v) gave a 77% stimulation in 14CO2 recovery. Pseudomonas aeruginosa metabolized acetonitrile to ammonia and acetic acid and biphenyl to benzoic acid. The bacterium also simultaneously utilized biphenyl as the sole carbon source and acetonitrile as the sole nitrogen source. However, biphenyl utilization increased only after the depletion of acetonitrile. Metabolites of the mixed substrate were ammonia and benzoic acid, which completely disappeared in the later stages of incubation. Nitrile hydratase and amidase were responsible for the transformation of acetonitrile to acetic acid and ammonia. PMID- 1913345 TI - Cell-free and cell-bound hemolytic activities of Proteus penneri determined by different Hly determinants. AB - A collection of 45 Proteus penneri strains was characterized with respect to their hemolytic activity and representative cell-free or only cell-bound hemolysin possessing strains were chosen for further study. Extracellular Proteus penneri hemolysin, which was investigated earlier by hybridization, reacted with monospecific antiserum against alpha-hemolysin of Escherichia coli. In this paper we also show, using the colony hybridization technique, that the alpha-hemolysin like determinant is widely distributed among Proteus penneri strains. Because one of the strains tested, which expressed a high activity of cell-bound hemolytic factor, did not carry such a Hly determinant, the presence of a second hemolysin is postulated. We cannot demonstrate any difference in hybridization patterns of alpha- and beta-hemolytic Proteus penneri strains and accumulation of the toxin molecule inside the cells was also not observed. The existence of another control mechanism, external to the hly operon, for hemolysin gene is suggested. PMID- 1913346 TI - Cloning and characterization of the nifA gene from Herbaspirillum seropedicae strain Z78. AB - A genomic library of Herbaspirillum seropedicae was constructed and screened for the nifA gene by complementation of a nifA mutant of Azospirillum brasilense (FP10). A recombinant plasmid, pEMS1, capable of restoring acetylene reduction activity in the mutant FP10, was isolated and found to hybridize to the nifA gene of Klebsiella pneumoniae. The results suggest that nifA is involved in the regulation of nif genes in H. seropedicae. PMID- 1913347 TI - Biodegradation of pentachlorophenol in soil: the response to physical, chemical, and biological treatments. AB - The effects of physical, chemical, and biological treatments on biodegradation of pentachlorophenol (PCP) were studied in a silt-loam soil contaminated with 175 mg PCP/kg and uniformly 14C-labelled PCP. Biodegradation of 14C-labelled PCP and technical-grade PCP were monitored over 210 days incubation. Mineralization of labelled PCP was significantly (p=0.05) influenced by soil treatments. Negligible biodegradation occurred in either the sterile control soil or the uninoculated control soil, with less than 1% of added 14C recovered as 14 CO2. Inoculation of unamended soil with a strain of Flavobacterium (ATCC 39723) known to degrade PCP increased biodegradation of PCP; approximately 60% of the [14C]PCP was recovered as 14CO2. Increased soil water content (60% versus 30% w/w) enhanced biodegradation (67% recovery of 14C as CO2), while increased chloride ion concentration and anoxic conditions were inhibitory (20 and 1% recoveries, respectively). Residual soil PCP concentrations were also influenced by various treatments. In the sterile control soil and noninoculated control, after 210 days incubation, concentrations of PCP were 143 and 1223 mg/kg, respectively, while the PCP concentration in the inoculated soil was 21 mg/kg. When soil organic matter was increased by adding finely ground red clover leaf and stem material, the residual PCP concentration was reduced to 6 mg/kg after 210 days. Increased soil water content resulted in a residual PCP concentration of 5 mg/kg. High pressure liquid chromatography of soil extracts revealed no accumulation of partial PCP degradation products. The results indicated that biodegradation of PCP in soil was significantly influenced by various soil amendments. PMID- 1913348 TI - The production of antibacterial tubing, sutures, and bandages by in situ precipitation of metallic salts. AB - Two procedures were used to modify gauze bandages, polyester sutures, silicone tubing, and polyvinyl chloride tubing. In one procedure, the materials were first modified by in situ precipitation of metallic hydroxides and then used to adsorb silver ions. In the second procedure, the materials were soaked in sodium pyrophosphate or sodium chloride, dried, and then soaked in silver nitrate. These procedures produced materials with silver deposited on the surface of the tubing and sutures and both on the surface and within the gauze fibers. The modified materials inhibited the growth of Pseudomonas aeruginosa. Escherichia coli, and Staphylococcus aureus in vitro. PMID- 1913349 TI - Changes in antigenic reactivity of Borrelia burgdorferi, the Lyme disease spirochete, during persistent infection in mice. AB - Adult laboratory mice, Mus musculus, were shown to be suitable experimental animals for studying infectivity, persistent infection, and in vivo antigenic changes of Borrelia burgdorferi. Sixteen mice were inoculated intraperitoneally with a low-passage culture of an uncloned strain of B. burgdorferi and 16 months later spirochetes were reisolated from the urinary bladder of 15 (94%) of the mice. Spirochetes recovered from the urinary bladder of one persistently infected mouse were tested for infectivity and found to be infectious when passaged into four laboratory mice. Western blot analysis of immune serum from each of the persistently infected mice demonstrated that spirochetes used to infect the mice reacted differently when compared with the spirochetes subsequently reisolated from the mice, demonstrating for the first time that changes in antigenic reactivity had occurred in the spirochete populations during persistent infection. PMID- 1913350 TI - The use of methanol extract of Leptospira interrogans in complement fixation tests for leptospirosis. AB - Methanol extracts were obtained from L. interrogans serovars icterohaemorrhagiae and canicola and L. biflexa serovar patoc. Human sera from 167 normal individuals and 40 patients with different infectious diseases tested by complement fixation tests showed negative reactions. Sera from 100 patients with a suspicion of leptospirosis were tested by complement fixation tests and microscopic agglutination reactions. Agreement of 84% was found for those two reactions. Positive microscopic agglutination tests at a dilution 1:20-1:400 with negative complement fixation tests were observed in 5% of patients and negative microscopic agglutination with complement fixation tests in the range of 1:20 1:1280 were observed in 11% of the cases. PMID- 1913351 TI - Electrotransformation in Salmonella typhimurium LT2. AB - Electroporation gives high efficiency of transformation in Salmonella typhimurium LT2, yielding 10(8)-10(9) electrotransformants per microgram of pBR322 DNA. Lipopolysaccharide (LPS) composition has little influence on electrotransformation efficiency by electroporation, unlike Ca2+ shock methods, which give ca. 10(6) transformants/microgram DNA with strains with Rc or Rd2 LPS, 10(4) transformants with most smooth and rough strains, and 10(2) transformants with strains with Re LPS. Thus cell envelope properties are less crucial in electrotransformation than in Ca2+ shock methods. The reciprocal restriction barrier between Escherichia coli K-12 and S. typhimurium LT2 reduces electrotransformation by ca. 100-fold, but host-restriction mutants reduce or eliminate the barrier. PMID- 1913352 TI - Recombinant interleukin-6 increases the intracellular and extracellular growth of Mycobacterium avium. AB - Human monocytes were isolated from the peripheral blood of normal donors and allowed to differentiate in vitro into macrophages. The susceptibility of these cells to infection with a virulent Mycobacterium avium and its modulation by some soluble factors was monitored. The virulent strain of Mycobacterium avium grew progressively in untreated macrophage monolayers. Interleukin-6 (IL-6) was tested for its ability to modulate the macrophage-mycobacteria interaction. Surprisingly, IL-6 was shown to increase M. avium growth in macrophage monolayers by twofold as compared with untreated cells, when added before or after infection. Moreover, addition of rIL-6 to replicating mycobacteria in vitro enhanced their growth two- to three-fold as compared with cultures treated with rIL-6 and a rabbit antiserum to rIL-6. Treatment with IL-6 and interferon-gamma (IFN-gamma) or IL-4 did not modify the growth promoting effect of IL-6 in human macrophages. Overall, our results suggest that IL-6 may contribute significantly to the pathogenesis of infections with M. avium by promoting mycobacterial growth. PMID- 1913353 TI - Prevention of fungal colonization and digestion of cellulose by the addition of methylcellulose. AB - When the attachment of cellulolytic rumen fungi to cellulose is blocked by the addition of methylcellulose, cellulose digestion is entirely inhibited. Even after these fungi have colonized and penetrated the cellulosic fibers of filter paper, the addition of methylcellulose effectively halts cellulose digestion. This effect of methylcellulose is accompanied by the complete inhibition of fungal attachment to cellulose fibers; the addition of methylcellulose does not affect the growth of these organisms on soluble substrates. We conclude that fungal cellulose digestion, like bacterial cellulose digestion, requires the spatial juxtaposition of the cellulolytic organism and its insoluble substrate. The simultaneous inhibition of both attachment and digestion by the same inhibitor suggests that these two processes are functionally linked in the fungi. PMID- 1913354 TI - Stability of plasmids in lactococci during extended incubation in growth media. AB - The stability of plasmids in Lactococcus lactis ssp. lactis strains C2 and ML3, and L. lactis ssp. cremoris strains ML1 and SC607, was investigated by extended incubation of bacterial cells in low nutrient media under acidic conditions. Strains were grown overnight (16-18 h) in skim milk and unbuffered medium (M17-) at 32 degrees C and subsequently held at that temperature for extended periods (greater than or equal to 96 h). Lac- variants were obtained from each strain in milk and (M17-) broth. The plasmid profiles of Lac- variants when compared with their parental Lac+ strains showed loss of one or more plasmid bands. None of the Lac- mutants showed loss of smaller plasmids (less than 5 MDa) indicating that smaller plasmids in lactococci are more stable under these conditions than larger plasmids (greater than 10 MDa). Concomitant loss of the Lac+ phenotype and plasmids by the method used in the present investigation may have application for isolating mutants devoid of one or more plasmids. PMID- 1913355 TI - Competition between strains of Escherichia coli with and without plasmid RP4 during chemostat growth. AB - Escherichia coli strains J53(nal) and J53(RP4) were grown together in glucose limited continuous cultures. Based on the measured growth kinetic constants of the two strains, take-over of the cultures by J53(RP4) was predicted. However, in practice, an initial period of predominance by J53(RP4) was always followed by a prolonged period in which relative numerical proportions of the two strains oscillated widely. This period of oscillation was removed or greatly reduced when the difference between the predicted growth-rate potentials of the two strains was increased by selection of a chemostat-adapted variant of J53(RP4). PMID- 1913356 TI - Occurrence of antibiotic and metal resistance and plasmids in Bacillus strains isolated from marine sediment. AB - Eleven hundred Bacillus strains isolated from marine sediment from the Minas Basin, Nova Scotia, Canada, were purified on LB agar supplemented with ampicillin, chloramphenicol, erythromycin, streptomycin, tetracycline, or mercuric chloride. Seventy-seven isolates were examined for plasmid DNA, and for resistance to 11 antibiotics, HgCl2, and phenylmercuric acetate. Minimum inhibitory concentrations of Ag, Cd, Co, Cu, and Zn were also determined. Forty three percent of antibiotic- and mercury-resistant strains contained one or more plasmids ranging from 1.9 to 210 MDa. Fifty-four percent carried plasmids greater than 20 MDa, and 97% were resistant to two or more metals. There was no correlation between plasmid content and resistance either to antibiotics or to mercurial compounds in these strains. Mercury-resistant isolates were unable to transform Hg2+ to volatile Hg0 by virtue of a mercuric reductase enzyme system (mer). Strains resistant to Hg2+ were investigated for their ability to produce H2S and intracellular acid-labile sulfide when grown in the absence and presence of HgCl2. Lower levels of H2S and intracellular sulfide were detected only in metal-resistant strains grown in the presence of HgCl2, suggesting that cellular sulfides complexed with Hg2+ in these strains. PMID- 1913357 TI - Comparison of the survival of Campylobacter jejuni and Campylobacter coli in culturable form in surface water. AB - Six Campylobacter jejuni and six Campylobacter coli strains were isolated from cows and pigs, and their survival in lake water was compared by viable counts. Campylobacter jejuni survived longer in culturable form than C. coli in untreated and membrane-filtered water both at 4 and 20 degrees C. This difference in survival time may be a reason why C. jejuni is generally isolated from surface waters more frequently than C. coli. Both species survived better in filtered than in untreated water. This suggests that predation and competition for nutrients affect the survival of both Campylobacter species in the aquatic environment. PMID- 1913358 TI - Cloning of a xylanase gene from Fibrobacter succinogenes 135 and its expression in Escherichia coli. AB - A genomic library consisting of 4- to 7-kb EcoRI DNA fragments from Fibrobacter succinogenes 135 was constructed using a phage vector, lambda gtWES lambda B, and Escherichia coli ED8654 as the host bacterium. Two positive plaques, designated lambda FSX101 and lambda FSX102, were identified. The inserts were 10.5 and 9.8 kb, respectively. A 2.3-kb EcoRI fragment that was subcloned from lambda FSX101 into pBR322 also showed xylanase activity. Southern blot analysis showed that the cloned EcoRI fragment containing the xylanase gene had originated from F. succinogenes 135. The cloned endo-(1,4)-beta-D-xylanase gene (pFSX02) was expressed constitutively in E. coli HB101 when grown on LB and on M9 medium containing either glucose or glycerol as the carbon source. Most of the beta-D xylanase activity was located in the periplasmic space. Zymogram activity stains of nondenaturing polyacrylamide gels and isoelectric focusing gels showed that several xylanase isoenzymes were present in the periplasmic fraction of the E. coli clone FSX02 and they probably were due to posttranslational modification of a single gene product. Comparison of the FSX02 xylanase and the xylanase from the extracellular culture fluids of F. succinogenes 135 and S85 for their ability to degrade oat spelt xylan showed that, for equal units of beta-D-xylanase activity, hydrolysis by the cloned gene product was more complete. However, unlike the unfractionated mixture of xylanases from F. succinogenes 135 and S85, the enzyme from E. coli FSX02 was unable to release arabinose from oat spelt xylan. PMID- 1913359 TI - Characterization of a Salmonella choleraesuis mutant that cannot multiply within epithelial cells. AB - A mutant of Salmonella choleraesuis was identified that could invade (enter) and penetrate through polarized monolayers of Caco-2 and MDCK epithelial cells at normal levels but was defective for intracellular multiplication within these cells. It was also able to survive inside cultured J774 macrophage cells. These bacteria remained inside membrane-bound vacuoles, which coalesced at later times in the perinuclear region of the epithelial cell. This mutant exhibited slightly slower growth rates in rich or minimal media than the parental strain but was normal for iron usage, phosphate usage, and anaerobic growth and was a prototroph. The mutant was completely avirulent when administered orally or intravenously to susceptible mice. These results suggest that the ability to multiply within eukaryotic cells may contribute to S. choleraesuis virulence. PMID- 1913360 TI - Accuracy of clinical diagnosis in parkinsonism--a prospective study. AB - Clinical diagnosis of Parkinson's syndrome (PS) is reasonably easy in most cases but the distinction between different variants of PS may be difficult in early cases. The correct diagnosis is not only important for counselling and management of patients but also in conducting pharmacological and epidemiological studies. There is very little critical literature on the pathological verification of the clinical diagnosis in PS. We report our 22 years experience to address that issue. Between 1968 and 1990, 65 PS patients came to autopsy. Complete data are available in 59 (M-50, F-19) cases. The initial diagnosis made by a qualified neurologist was idiopathic Parkinson's disease (IPD) in 43 cases. Of those 28 (65%) had Lewy body pathology. After a mean duration of 12 years the final diagnosis was IPD in 41 cases which was confirmed in 31 (76%). The IPD could not be clinically distinguished from cases with severe substantia nigra neuronal loss without inclusions or from those with neurofibrillary tangle inclusions and neuronal loss at the anatomical sites typically involved in IPD. All progressive supra-nuclear palsy, olivopontocerebellar atrophy, Jakob-Creutzfeldt's disease and the majority of the multiple system atrophy cases were diagnosed correctly during life. The correct clinical diagnosis in most non-IPD variants of PS was possible within 5 years of onset (range: 2 months to 18 years). We recommend that studies aimed at including only the IPD cases restrict the enrollment to those cases that have had PS motor manifestations for five years or longer duration. PMID- 1913361 TI - Parkinson's disease and exposure to rural environmental factors: a population based case-control study. AB - To determine whether a history of exposure to rural environmental factors leads to an increased likelihood of developing idiopathic Parkinson's disease, we conducted a case-control study of 130 cases and 260 randomly selected community controls (matched with the cases by sex and age +/- 2.5 years at a ratio of 2 controls: 1 case) in the city of Calgary. The data were collected by personal interviews and were analyzed using conditional logistic regression for matched sets. The ages of the cases ranged from 36.5 to 90.7 years (mean = 68.5 +/- 11.3 years). The mean age at diagnosis was 61.1 +/- 12.4 years. The mean duration of disease was 7.8 +/- 0.6 years. Eleven (9.1%) cases were diagnosed before age 40. In this sample from the Province of Alberta, Canada, no significant increase in risk for Parkinson's disease was associated with a history of rural living, farm living, or well water drinking in early childhood or at any time during the first 45 years of life. PMID- 1913362 TI - Two types of spheroid bodies in the nigral neurons in Parkinson's disease. AB - Dendritic spheroid bodies (SBs) and Lewy bodies (LBs) were identified in comparable numbers in the substantia nigra pars compacta (SBC) of nine parkinsonian cases and one case of striatonigral degeneration but were not found in cases of Huntington's disease or neurologically normal controls. The immunohistochemical profile of the SBs in dystrophic dendrites of nigrostriatal dopaminergic neurons was remarkably similar to that of the LBs found within dendrites or free of the SNC neuropil. Both types of inclusions stained positively with antibodies to tyrosine hydroxylase, ubiquitin and microtubule associated protein-2 (MAP2), and negatively for Tau-2, although they had different ultrastructural appearances. A few intracellular LBs were stained by antibodies to neurofilament proteins (NFs) 68, 160, and 200 kD, but dendritic SBs and extracellular LBs were not so stained. These data indicate that dendritic SBs and extracellular LBs may have a common molecular pathogenetic origin in Parkinson's disease. On the other hand, the SBs seen in the pars reticulata (SNR) and in the distal nigrostriatal axons even in control cases were generally stained by antibodies to NFs and ubiquitin but not to MAP2. This latter staining pattern in similar to that shown by SBs in the anterior horn in ALS and in the cerebellum of neurologically normal brains and is believed typical of axonal as opposed to dendritic SBs. PMID- 1913363 TI - The case for conservative management of venous angiomas. AB - Venous angiomas (developmental venous anomalies) are vascular malformations increasingly recognized in general neurosurgical or neurological practice. They are associated with intracranial hemorrhage, seizures, or progressive neurological deficits or found as incidental findings in patients who present with headaches or have neuroimaging studies for investigation of unrelated neurological disorders. Since venous angiomas drain normal cerebral tissue within a functionally normal arterial territory, resection can lead to venous infarction. This report studies 27 patients with venous angiomas, all of whom had conservative treatment. The venous angioma was considered to be responsible for the onset of neurological symptoms in 14 patients (7 with hemorrhage, 3 with hemorrhage and seizures, 2 with seizures, one with an extrapyramidal movement disorder, and one with motor deficit). Thirteen patients had incidental lesions (8 with headache, and 5 with unrelated neurological symptoms). Ten venous angiomas were in the posterior fossa; seven in the cerebellum. Location did not correlate with symptomatic presentation. No patient with hemorrhage required surgical evacuation of the hematoma. No patient died or had significant morbidity during the follow-up interval (mean of 3.7 years). Venous angiomas are low flow, low resistance vascular malformations, many of which are not associated with neurological sequelae. Our series supports the concept that surgical removal or radiosurgical obliteration should not be performed unless a patient has a second life threatening hemorrhage. PMID- 1913364 TI - Myotonic dystrophy: an electrophysiological study of cognitive deficits. AB - Patients with Myotonic Dystrophy (MyD) frequently suffer from a dysfunction of the primary sensory pathways, as documented by abnormalities of short-latency evoked potentials. Impairment of intellectual functions has been less extensively investigated. Short-latency brainstem auditory evoked potentials (BAEPs) as well as long-latency auditory event-related potentials (ERPs) were recorded from 5 female and 6 male patients affected by MyD. A simple discrimination ("oddball") paradigm was used to record ERPs to tones from Fz, Cz, Pz. Both BAEPs and ERPs were significantly altered as compared to normals. BAEP abnormalities were detected in 9 patients and ERP components N2 and P3 were delayed or absent for all patients, who nonetheless correctly discriminated between tones. These data indicate that CNS dysfunction in MyD involves not only primary sensory systems but also neural mechanisms underlying cognitive events and ERP generation. PMID- 1913366 TI - Dissociated loss of vibration, joint position and discriminatory tactile senses in disease of spinal cord and brain. AB - The clinical functions of the posterior columns of the spinal cord and the signs of disease of these structures have been debated for years. Todd in 1847 and Schiff in 1858 knew the functions of the posterior columns and 10 years later Brown-Sequard knew as well. Reynolds, Romberg, and Duchenne, each described a posterior column syndrome based on a disease in which the primary lesion was not in the posterior columns. In the last 150 years almost every white matter structure of the cord has been credited with serving the sensations that we now know are a function of the posterior columns. Vibration, joint position and movement as well as discriminatory touch each seem to be served by separate fibres of the posterior columns and medial lemniscus. There is evidence of this in cat and man. These sensations may be lost individually, totally, or in certain stereotyped combinations. Vibration or joint sense is commonly lost alone. When a discriminatory touch sensation is lost with one other sense, it is almost inevitably joint position sense. Absent discriminatory touch and vibration sense with normal joint position sense appears to be unknown. This functional separation continues into the thalamus. At the highest level there is no evidence that vibration sense has any conscious somatosensory cortical affiliation, while joint position and discriminatory touch senses definitely do. PMID- 1913365 TI - Treatment of heredo-degenerative ataxias with amantadine hydrochloride. AB - Amantadine hydrochloride (AH) was administered (200 mg/day) for more than three months to 17 patients with Friedreich's ataxia (FA) and to 12 patients with olivopontocerebellar atrophies (OPCA) in an open clinical trial. Reaction time (RT) and movement time (MT) with the right and left hand were measured before and after treatment. A striking improvement on both RT and MT was observed in the OPCA group (on seven out of eight measures), whereas in the FA patients improvement was seen only in two out of four MT measures with no improvement in RT. Both groups had low levels of homovanillic acid (HVA) in their cerebrospinal fluid before treatment, relative to their controls. However, improvement with AH was not related to HVA levels. PMID- 1913367 TI - Modulation of locomotor patterns and spasticity with clonidine in spinal cord injured patients. AB - This double blind cross-over study, involving 9 chronic spinal cord injured (SCI) patients (6 paraplegic and 3 paretic), was a first attempt to investigate the effects of the noradrenergic agonist, clonidine, on the modulation of the locomotor pattern and spasticity in patients with spinal cord lesions. Electromyographic (EMG), footswitch and video recordings were made as the patients walked on a treadmill with the support of an overhead harness if needed. Overground locomotion was also assessed in the paretic patients. All 3 spastic paretic patients had kinematic deviations and abnormal EMG recruitment profiles during the premedication or placebo sessions. With clonidine therapy one patient demonstrated a marked improvement in locomotor function. This patient progressed from non-ambulation to limited independent ambulation as the extent of coactivation in antagonist muscles decreased. The other 2 paretics who presented limited spasticity showed minimal changes while on clonidine. In the paraplegic patients, clonidine did not elicit locomotor activity, although there were marked reductions in stretch reactions and clonus during assisted locomotion. They remained incapable of locomotion, either during the control period or during the clonidine therapy. These results indicate that clonidine may be a potentially useful medication for both locomotion and certain manifestations of spasticity in SCI patients but further investigation is warranted. PMID- 1913368 TI - A movement-associated fast rolandic rhythm. AB - A stereotyped 32 Hz rolandic rhythm maximal over the mesial cortex and occurring only with voluntary movement is described in a patient with tonic postural seizures. This abnormal but nonictal rhythm, which is probably generated subcortically, is expressed synchronously at the level of the cortex and peripherally in the EMG. PMID- 1913369 TI - Accessory nerve palsy: a review of 23 cases. AB - In a series of 23 patients, the commonest cause of accessory nerve palsy was surgical trauma at the time of lymph node biopsy. The less common causes were penetrating or blunt trauma and a few were of spontaneous onset. There was involvement of adjacent motor sensory nerves in about half of the patients. The prognosis was better following blunt trauma, stretch injuries and after a spontaneous onset. The anatomical relationships of the accessory nerve and aspects of the clinical picture and management are discussed. PMID- 1913370 TI - Entrapment of an accessory superficial peroneal sensory nerve. AB - A 29 year old man had an accessory branch of the superficial peroneal nerve which entered the foot by rostro-caudally traversing the lateral malleolus laterally. The nerve was entrapped by a fascial band, resulting in pain over the lateral malleolus and dorsum of foot. Symptoms resolved when the nerve was surgically released. PMID- 1913371 TI - Dementia with leukoencephalopathy in systemic lupus erythematosus. AB - Neurologic manifestations, afflicting up to 70% of SLE patients, include psychosis, seizures, chorea, neuropathies, and stroke. MRI is useful in evaluation of lupus patients and several reports have documented cerebral atrophy or focal hyperintensities. We report an unusual MRI appearance in a 56-year-old woman with SLE, diagnosed on the basis of pleuritis, lymphopenia, anti-DNA antibodies, and neurologic involvement. She reported recent onset of Raynaud's phenomenon and generalized macular rash. She presented after two months of gradual deterioration with memory loss, flattened affect, dysphagia, dysarthria, anomia, and somnolence, without focal neurologic signs. Investigations included elevated ESR, reduced complement, normal CSF without oligoclonal bands, negative viral serology, normal hormone and vitamin levels, normal renal and hepatic function. Neuropsychologic testing showed widespread impairment (WAIS-R: FSIQ-63; WMS-69; DRS-98; RCPM-14; WAB AQ-78.8). CT was normal but MRI showed strikingly symmetric, confluent hyperintensities extensively involving cerebral and cerebellar white matter on T1 and T2 weighted scans. Basal ganglia and subependymal and subcortical white matter were spared. Treated with prednisone, the patient made a gradual, but incomplete, recovery. These MRI findings may reflect widespread vasculopathy or direct immunologic brain insult with or without immunologic blood-brain barrier disruption. PMID- 1913373 TI - Pathological and molecular biological features of a myelopathy associated with HTLV-1 infection. AB - We report the pathological and molecular biological findings of human T-cell lymphotropic virus type 1 (HTLV-1) infection of the spinal cord in a patient with a chronic progressive myelopathy. Light microscopy disclosed loss of myelin and axons, thickening of blood vessels and a lymphocytic cell infiltrate in the spinal cord especially at the cervical and thoracic levels. Electron microscopy confirmed the vascular appearance seen with light microscopy but virus particles were not observed. The HTLV-1 gag gene could be amplified (by polymerase chain reaction) from cervical spinal cord tissue while not from elsewhere in the neuroaxis. The presence of HTLV-1 genomic material in spinal cord tissue has not been previously reported. PMID- 1913372 TI - Bulbo-pontine paralysis with deafness: the Vialetto-Van Laere syndrome. AB - A Caucasian girl developed slowly progressive sensory neural deafness and bulbar and spinal muscle weakness typical of the Vialetto-Van Laere syndrome. As the condition progressed the major disabilities became dysphagia, respiratory muscle weakness and postural hypotension. Treatment with gastrostomy feedings, oxygen and fludrocortisone acetate produced worthwhile functional improvement. PMID- 1913374 TI - Benign brainstem hemorrhage. AB - Most patients with brainstem hemorrhage have a poor prognosis. There are occasional reports of a favorable outcome with hematomas restricted to the mid brain region. We report two patients with hematomas within the lower brainstem (pons and medulla) who made a good recovery. Diagnosis was unsuspected until the cranial CT scan was done. Angiography was normal in both cases. Recovery was excellent in one and fair in the second patient. Patients with medullary hemorrhage are at risk for aspiration and may suddenly develop respiratory arrest and therefore should be carefully observed. Our review of the literature suggests that with some small brain-stem hemorrhages recovery is good to excellent and recurrences are rare. PMID- 1913375 TI - Pneumocephalus following treatment of esthesioneuroblastoma. AB - The course of a patient with an olfactory neuroblastoma treated with conventional doses of chemotherapeutic agents and radiotherapy is presented. The patient survived 34 months after tumour necrosis with resultant pneumocephalus requiring surgical intervention. PMID- 1913376 TI - A footnote to medical history: David Alexander Shirres on spinal cord regeneration. PMID- 1913377 TI - Minimal standards for electroencephalographic laboratories. Canadian Society of Clinical Neurophysiologists. PMID- 1913378 TI - An update on the carotid endarterectomy study. PMID- 1913379 TI - Waiting for weight loss. PMID- 1913380 TI - The natural history of suspected scaphoid fractures. PMID- 1913381 TI - The case of a reluctant mule. PMID- 1913382 TI - Spontaneous bacterial peritonitis in a healthy male caused by Streptococcus viridans. PMID- 1913383 TI - Diagnostic peritoneal lavage: the Cook County Hospital experience. PMID- 1913384 TI - Cardiac function in massively obese patients and the effect of weight loss. AB - Massively obese patients are at increased risk for heart disease. Blood volume and capillary flow are increased to supply the excess body mass, and there is a concomitant increase in preload and, often, afterload. The heart compensates for the expanded blood volume by increasing stroke volume and cardiac work to provide increased cardiac output. The result is left ventricular dilatation followed by eccentric left ventricular hypertrophy. Cardiac compensatory reserve is limited, leading, at times, to overt congestive failure. After reduction of the excess body fat, most of the cardiovascular derangements appear to reverse. The authors review the effect of massive obesity on the heart and the cardiovascular consequences of weight reduction. PMID- 1913385 TI - A therapeutic window for carotid endarterectomy in patients with asymptomatic carotid stenosis. AB - The natural history of asymptomatic carotid stenosis was prospectively and systematically studied in 500 patients by clinical observation and carotid Doppler ultrasonography. In the 40% of carotid arteries (398) with an initial stenosis of over 35%, there were apparently two separate populations, with a cutoff point of 85% stenosis. There were 79 ischemic cerebral events (54 transient ischemic attacks and 25 strokes) among the 500 patients during 60 months of follow-up, predominantly in the severe-stenosis (more than 75%) group, with few events occurring in the near-or total-occlusion (95% to 100% stenosis) group; the highest incidence was in patients whose arteries had 75% to 90% stenosis. These observations indicate a critical degree of carotid stenosis at which stroke risk becomes maximal, declining as the artery becomes occluded. These findings suggest that there may be a "window" for carotid endarterectomy in patients with asymptomatic carotid stenosis, when the stroke risk may be high enough (5.5%/year) to warrant surgery. PMID- 1913386 TI - Is positive diagnostic peritoneal lavage an absolute indication for laparotomy in all patients with blunt trauma? The Montreal General Hospital experience. AB - The authors review the use of diagnostic peritoneal lavage (DPL) at The Montreal General Hospital between 1982 and 1987. Fifty-two of 254 patients admitted with a diagnosis of blunt abdominal trauma underwent DPL: results of the procedure were negative in 23 and positive in 29 (grossly positive in 27). Twenty-one of the 23 patients with negative findings were managed nonoperatively; the other 2 underwent laparotomy, which revealed no abnormalities. Nineteen of the 29 patients with positive findings were managed by immediate laparotomy; the other 10 were managed conservatively. The mean (+/- standard deviation) injury severity score (ISS) in the latter group was 13.1 +/- 8.01. The group managed by immediate laparotomy had an ISS of 25.91 +/- 12.81 (p = 0.007). The number of patients suffering from class I or class II shock in the group managed nonoperatively was significantly (p = 0.045) larger than those in the group managed by laparotomy. The authors conclude that a positive result DPL is not a sine qua non for immediate laparotomy in all patients with blunt abdominal trauma. A selective approach can be taken in these patients, considering the severity of the associated injuries and the patient's hemodynamic status. Intensive-care monitoring must be available. PMID- 1913387 TI - Long-term results after omental patch repair in patients with perforated duodenal ulcers: a 5- to 10-year follow-up study. AB - Ninety-two patients with perforated duodenal ulcers were treated at two hospitals in St. John's. Five patients were managed conservatively, and the remainder received omental patch closure. All were prescribed histamine receptor antagonists. No patient had a definitive ulcer operation. Seventy-five patients were followed up for 5 to 10 years. Fourteen patients who had been taking ulcerogenic medications had a low recurrence rate (7%); the other 61 patients who had not been taking ulcerogenic medications had a high recurrence rate (77%). Use of an omental patch is effective treatment for perforated duodenal ulcers and provides long-term benefit for patients whose perforations are associated with ulcerogenic medications. Selected patients who have not been taking ulcerogenic medication are better treated by definitive ulcer surgery at the time of perforation. PMID- 1913388 TI - Postoperative heterotopic ossification in children: a comparison of children with spina bifida and with cerebral palsy. AB - The authors reviewed 250 consecutive myotomies and tenotomies performed on the hips of 186 children. Two groups were studied: 162 children with cerebral palsy and 24 children with spina bifida. In total 19 children were found to have heterotopic ossification postoperatively. The incidence of heterotopic ossification was 21% in the spina bifida group and 8.6% in the cerebral palsy group. The most severe cases were in children with thoracic myelomeningocele. Only one child with lumbar myelomeningocele had ossification, and it was mild. This difference was statistically significant. Two children with thoracic spina bifida had severe ossification and abduction contractures requiring resection of the bony mass. Recurrence was successfully prevented by a course of radiotherapy. PMID- 1913389 TI - Liver transplantation with calcific sclerosis of the portal vein. AB - Thrombosis or phlebosclerosis of the portal vein is an infrequent finding during the preoperative evaluation of a potential liver transplant recipient. Occasionally the process extends proximally into the superior mesenteric vein. This precludes conventional methods of portal venous reconstruction, necessitating reconstitution of portal venous inflow during liver transplantation through a venous conduit. The authors present a case of calcific phlebosclerosis of the portal and distal superior mesenteric veins that was delineated during preoperative imaging. This case emphasizes the importance of visualizing both the portal and superior mesenteric veins during the preoperative assessment, when patency of the portal vein is questionable. When the obliterative process extends into the distal superior mesenteric vein the authors recommend construction of the venous conduit from the proximal superior mesenteric vein as a pre-emptive manoeuvre before dissection of the recipient's liver and hilar structures. The venous conduit is then ready for immediate use during engraftment, thereby maintaining the shortest possible anhepatic time. PMID- 1913390 TI - Inflammatory pseudotumours of the lung: two cases and a review. AB - A discrete pulmonary mass lesion has different implications in children and in adults. Although infectious, congenital and metastatic etiologies are part of the differential diagnosis, inflammatory pseudotumour of the lung, or plasma cell granuloma, has emerged as the most common entity. The authors describe two patients with this poorly understood lesion and review the current state of knowledge. Both patients were young (4 and 5 years) and had recurrent lower respiratory tract infections; one patient was asthmatic. Both had persistent cough, and discrete lung lesions were apparent radiologically. Both children were treated by thoracotomy and excision of the tumour. There were no operative complications, and the convalescent period was uncomplicated. There were no signs of recurrence at follow-up 1 and 2 years postoperatively. This lesion is almost always benign, but aggressive behaviour has been documented. The authors recommend prompt conservative surgical excision. PMID- 1913392 TI - Laser therapy of vulvar lichen sclerosus et atrophicus. AB - Seven patients with a histologic diagnosis of lichen sclerosus et atrophicus of the vulva were treated by laser ablation of the affected area to a depth of 1.0 to 2.0 mm. The inpatient procedure was performed under general anesthesia with a carbon dioxide laser unit. Healing was complete 6 weeks postoperatively. All but one patient was free of recurrent symptoms at follow-up, which ranged from 12 to 37 months. Laser ablation is an acceptable treatment for patients who have symptoms due to lichen sclerosus of the vulva that are refractory to other measures. PMID- 1913391 TI - Aerosol ventilation scintigraphy in the evaluation of bronchopleural fistula: a case report and literature review. AB - Radioaerosol scanning is simple to perform and is widely used in conjunction with perfusion imaging to detect pulmonary emboli. It may also be a valuable tool for the early diagnosis of postpneumonectomy bronchopleural fistula. The authors present an illustrative case in which radioactive aerosol imaging was used to confirm a bronchopleural fistula secondary to pneumonectomy for squamous cell carcinoma. PMID- 1913393 TI - Diagnostic peritoneal lavage as an indicator for therapeutic surgery. AB - Diagnostic peritoneal lavage (DPL) has been reported to be extremely accurate in identifying intra-abdominal injury. Many studies, however, fail to indicate clearly if the procedure is helpful in determining which patients require truly therapeutic surgical intervention, because not all injuries need such surgery. In this study the authors reviewed the charts of 174 patients with blunt abdominal trauma and, by applying strict criteria to define a therapeutic laparotomy, sought to determine, retrospectively, whether DPL was useful for indicating the need for therapeutic surgery. Although 94% of patients with positive findings from DPL underwent a laparotomy, only 65% underwent one that was clearly of therapeutic value. Although other factors may have partially contributed to the discrepancy between these results and those generally referred to in the trauma literature, this study suggests that criteria providing a strict definition of a therapeutic laparotomy must be universally applied when analysing the value of DPL. PMID- 1913394 TI - Duodenal ulcer hemorrhage in the puerperium. AB - Hemorrhage from a peptic ulcer during pregnancy is a rare complication that occurs most frequently near term or in the puerperium. A case of massive hematemesis from a duodenal ulcer on the third puerperal day is described. Emergency surgery with vagotomy and pyloroplasty was performed. The mother had no symptoms of peptic ulceration until the onset of mild abdominal pain 4 days before delivery. PMID- 1913395 TI - Gastric volvulus--a late complication of gastrostomy. AB - Two cases of gastric volvulus are reviewed. Both patients were nonverbal, mentally handicapped children, who were fed through a gastrostomy. They had intermittent intolerance to bolus feeds through the gastrostomy, accompanied by abdominal distension and vomiting of gastric contents. One had a previous partial fundoplication and gastrostomy, and the other had had two pyloroplasties and gastrostomy. The axis of torsion ran from the esophagogastric junction to the gastrostomy site. Both children were treated by detorsion and gastropexy. It is postulated that the gastrostomy served as a fixed point for the volvulus. This was facilitated by the chronically dilated stomachs induced by bolus feeds. These two cases are reported to alert the clinician to this possibility when a neurologically impaired child with a gastrostomy presents with feeding difficulties and persistent vomiting. PMID- 1913396 TI - Surgical treatment of achalasia in a general hospital. AB - The authors report their experience with 43 patients treated for achalasia of the esophagus in a general hospital between 1971 and 1986. Patients were divided into two groups according to the type of surgery performed: group 1--29 patients treated by Heller myotomy, performed by nine general surgeons between 1971 and 1983; and group 2--14 patients treated by transthoracic Heller myotomy with the addition of a Belsey Mark-IV fundoplication. Dysphagia was reduced postoperatively in 82.6% of patients in group 1 and 92.8% of patients in group 2. Three patients in group 1 and one patient in group 2 had persistent dysphagia. Ten patients in group 1 had symptoms of gastroesophageal reflux (5 of them required a second antireflux procedure). In group 2, one patient had symptoms of gastroesophageal reflux, but was treated successfully medically. There was no difference in the degree of relief of dysphagia between the abdominal and thoracic approach, or in whether the operation was performed by a general surgeon without specific experience in the treatment of achalasia. The addition of a fundoplication to a Heller myotomy appeared to lessen the problem of postoperative gastroesophageal reflux. Since the Heller myotomy is technically difficult and may lead to obstruction of the poorly emptying esophagus the authors recommend that it be used selectively and only by the experienced esophageal surgeon. PMID- 1913397 TI - The Akin procedure in hallux valgus. AB - A retrospective study of 28 Akin procedures was undertaken to assess their results. Patient satisfaction, clinical findings and roentgenographic measurements were evaluated after follow-up periods of 12 to 42 months. The outcome was excellent in nearly 60% of the patients, especially those whose discomfort was related to the laterally deviated great toe and to the prominence of the first metatarsal head. PMID- 1913398 TI - Pneumatic antishock garment decreases hemorrhage and mortality from splenic injury. AB - The effect of the pneumatic antishock garment (PASG) in controlling hemorrhage and death from splenic injury was studied in a canine model. Twelve (two groups of 6) anesthetized dogs had their spleens crushed. Carotid blood pressure, carotid blood flow, splenic artery flow and abdominal aortic flow, as well as the death rate and blood loss, were measured. Group 1 dogs did not have PASG inflation, but group 2 dogs had PASG inflation to an intraperitoneal pressure of 60 mm Hg. All group 1 dogs died within 27 to 58 minutes, but all group 2 dogs survived. Blood loss was 9.4 +/- 1.4 mL/min in group 1 and 1.6 +/- 0.9 mL/min in group 2. In group 1 carotid artery blood pressure, carotid artery flow, splenic artery flow and abdominal aortic flow fell from 120 +/- 10 mm Hg, 284 +/- 12 mL/min, 194 +/- 18 mL/min and 285 +/- 10 mL/min respectively to 0 with death of the animals. By 2 hours in group 2 dogs the carotid artery blood pressure had dropped from 116 +/- 12 to 99 +/- 12 mm Hg, and over the same period carotid artery flow, splenic artery flow and abdominal aortic flow fell from 296 +/- 8 mL/min, 190 +/- 26 mL/min and 279 +/- 16 mL/min respectively to 259 +/- 14 mL/min, 39.0 +/- 6 mL/min and 45 +/- 11 mL/min respectively. Thus, inflation of the PASG maintained carotid artery blood pressure wh ile decreasing splenic, abdominal and aortic flow as well as splenic hemorrhage, with a decrease in the death rate, over a 2-hour period. PMID- 1913399 TI - Expanded polytetrafluoroethylene patch in hernia repair: a review of clinical experience. AB - The use of an implantable prosthetic material is often needed to repair inguinal and incisional hernias, especially when the local tissue is of poor quality or there is a large defect that would cause excessive tension if closed without patching with prosthetic material. An expanded polytetrafluoroethylene (ePTFE) patch was used in 37 patients between May 1986 and May 1990 to repair 25 direct inguinal and 12 incisional hernias. There was one recurrence in the group of patients with incisional hernia but none in those with a direct inguinal hernia. The recurrence was due to poor collagen ingrowth into the patch and subsequent herniation between two sutures. There were no complications due to infection, adhesions, erosion or fistulization. On the basis of this clinical experience, the authors conclude that the ePTFE patch is almost an ideal abdominal wall substitute, but that because of poor anchorage with tissue reaction alone, the success of the repair depends on the technique of suture placement. PMID- 1913400 TI - Use of a urethral splent in one-stage hypospadias repair. AB - Over a 9-month period, 28 patients with distal penile or more proximal hypospadias underwent one-stage surgical repair. Bladder drainage was achieved in the traditional fashion with either an indwelling Foley catheter or suprapubic catheter or by using a modified urethral silicone stent ("splent"). Twenty-two patients had repair with a perimeatal skin flap, and the remaining six patients had major urethral reconstruction with a vascularized preputial island flap. Use of the urethral splent was associated with shorter postoperative hospitalization and minimal short-term complications. The authors' experience has shown that use of a urethral splent for urinary drainage is efficient and effective in postoperative management after hypospadias repair. PMID- 1913401 TI - High-pressure injection injuries. AB - High-pressure injection injuries are potentially disabling forms of trauma. Three cases are presented of patients who sustained high-pressure injuries from paint, air and water. Injuries from paint require emergency surgical debridement and exploration because of the extreme tissue toxicity of the injected material. The patient in this study had a favourable outcome after delayed closure of his wound and extensive physiotherapy. High-pressure injuries resulting from air and water can be managed conservatively, as in the two patients reported in this paper. Their treatment included tetanus prophylaxis, irrigation, dressings, splinting, admission to hospital, intravenous broad-spectrum antibiotics, radiologic assessment and careful neurovascular evaluation. Surgical debridement and exploration were not necessary. PMID- 1913402 TI - The fee-for-service system should be replaced. PMID- 1913403 TI - Understanding psychotropic drugs. PMID- 1913404 TI - The chartless office: some practical considerations. PMID- 1913405 TI - Thinking about moving south? PMID- 1913406 TI - A need for population-based studies of health and safety risks in Canadian agriculture. PMID- 1913407 TI - The right to remain psychotic. PMID- 1913409 TI - Use of reminders for preventive procedures in family medicine. AB - OBJECTIVE: To compare the effectiveness of three computerized reminder systems in the delivery of five preventive procedures in family practice. DESIGN: Prospective, randomized, controlled study. SETTING: Ottawa Civic Hospital Family Medicine Centre. PARTICIPANTS: Of 8502 patients 15 years of age or more who were not in a hospital or institution 5883 were randomly assigned, by family, to a control group, a physician reminder group (passive) or a telephone or letter reminder group (active). The remaining 2619 patients were not included in the randomized portion of the study but were monitored. INTERVENTION: During 1 year the patients in the active reminder groups received a telephone call or letter reminding them of any overdue preventive procedures; for those in the passive reminder group the physician was reminded at an office visit to provide any overdue service. OUTCOME MEASURE: Rates of completion of the preventive procedures required. MAIN RESULTS: All three reminder systems significantly improved the delivery of preventive services (p less than 0.001). The procedure completion rates were 42.0% in the letter reminder group, 42.0% in the telephone reminder group, 33.7% in the physician reminder group and 14.1% in the randomized control group. The use of a letter was more cost-effective than the telephone system, but the physician reminder system was the most cost-effective. CONCLUSION: Computerized reminder systems do improve the delivery of preventive services in family practice. PMID- 1913408 TI - Periodic health examination, 1991 update: 5. Screening for abdominal aortic aneurysm. Canadian Task Force on the Periodic Health Examination. PMID- 1913410 TI - Neuroleptic malignant syndrome without the use of neuroleptics. PMID- 1913411 TI - Fish oils in the treatment of hypertriglyceridemia. PMID- 1913412 TI - A case of Alzheimer's disease with neuropathological findings. 1936. PMID- 1913413 TI - Moving a practice from northern Ontario to India. PMID- 1913414 TI - The ethics of everyday practice. PMID- 1913415 TI - Stock up on health insurance, province warns Ontarians heading to US. PMID- 1913416 TI - There should be more to life than medicine, author warns workaholic MDs. PMID- 1913417 TI - Federal disaster-planning exercise brings 30 emergency MDs together for week-long course. PMID- 1913418 TI - Amended Bill 120 finally law in Quebec but some physicians remain concerned. PMID- 1913419 TI - Wearing a wife-assault-prevention button: impact on a family practice. PMID- 1913420 TI - Incest can have devastating emotional and physical consequences, women physicians told. PMID- 1913421 TI - Administrative blunders in Third World medicine. PMID- 1913422 TI - Emergency care and the patient in the long-term care facility. PMID- 1913423 TI - Bicycle helmet campaign. PMID- 1913424 TI - Access to information for adult adoptees. PMID- 1913425 TI - Occupational therapy in the community. PMID- 1913426 TI - Snake oil and Caesar salad: the ethics of physician and pharmaceutical relationships. PMID- 1913427 TI - Sterilization and disinfection in the physician's office. AB - OBJECTIVE: To review the principles and practice of sterilization and disinfection of medical instruments in the office setting. DATA SOURCES: Searches of MEDLINE for articles published from 1980 to 1990 on disinfection, sterilization, cross infection, surgical instruments and iatrogenic disease, bibliographies, standard texts and reference material located in a central processing department. STUDY SELECTION: We reviewed surveys of decontamination practices in physicians' offices, reviews of current recommendations for office decontamination procedures, case reports of cross infection in offices and much of the standard reference material on decontamination theory and practice. DATA SYNTHESIS: There have been few surveys of physicians' decontamination practices and few case reports of cross infection. Office practitioners have little access to practical information on sterilization and disinfection. CONCLUSION: The increasing threat of cross infection from medical instruments calls for greater knowledge about decontamination. We have adapted material from various sources and offer a primer on the subject. PMID- 1913428 TI - Factors affecting physicians' decisions on caring for an incompetent elderly patient: an international study. AB - OBJECTIVES: To determine what treatment decisions physicians will make when faced with a hypothetical incompetent elderly patient with life-threatening gastrointestinal bleeding and to examine the relative importance of physician characteristics and factors (legal and ethical concerns, hospital costs, level of dementia, patient's age, physician's religion, patient's wishes and family's wishes) in making those decisions. DESIGN: Survey. SETTING: Family practice, medical and geriatrics rounds in academic medical centres and community hospitals in seven countries. PARTICIPANTS: Physicians who regularly cared for incompetent elderly patients. MAIN OUTCOME MEASURES: A self-administered questionnaire describing the elderly patient. Respondents were asked to choose one of four levels of care and to identify the level of importance factors had in making that decision. Older physicians, those less concerned about litigation, those for whom the level of dementia was important and those for whom the patient's age was important were expected to give less aggressive care than the other physicians. MAIN RESULTS: Supportive care was chosen by 8.1% of the respondents, limited therapeutic care by 41.5%, maximum therapeutic care without admission to the intensive care unit (ICU) by 32.2% and maximum care with admission to the ICU by 18.2%. The patient's wishes were reported by 91.0% as being extremely or very important in choosing the treatment. Stepwise logistic regression analysis revealed that the following variables independently predicted the level of treatment: level of dementia, country of residence, duration of practice, legal concerns, patient's age and ethical concerns. These factors were significantly correlated with the physicians' treatment choices (p less than 0.05). CONCLUSIONS: The importance that the physicians placed on the level of dementia was the strongest predictor of the level of care that would be provided. A societal consensus on the influence of cognitive function on the appropriate level of care as well as training of physicians in ethical issues are required. PMID- 1913431 TI - Wilson's disease presenting as Heinz-body hemolytic anemia. PMID- 1913430 TI - Diagnostic delay after dimenhydrinate use in vomiting children. AB - OBJECTIVE: To determine whether the use of dimenhydrinate was associated with delay in the diagnosis and management of treatable illnesses or with direct adverse effects in children with vomiting presenting to an emergency department. DESIGN: Questionnaire survey and review of drug reaction and telephone inquiry records. SETTING: The emergency department of a tertiary care children's hospital and a provincial poison information centre. PATIENTS: The parents of 148 children who presented with vomiting completed the questionnaire. The database at the poison information centre included 474 reports of adverse drug reactions over an 8-year period and 105 reports of telephone inquiries over a 4-year period. MAIN RESULTS: Twenty-one (14%) of 148 children had received dimenhydrinate before arrival at the emergency department. The patients who had received dimenhydrinate were more likely than the others to present more than 12 hours after the onset of vomiting (14 [67%] of 21 v. 43 [34%] of 127, p less than 0.01). The discharge diagnoses for those who had received dimenhydrinate included asthma, pelvic inflammatory disease and urinary tract infection. No clinically important direct adverse reactions to dimenhydrinate were documented. CONCLUSIONS: The use of dimenhydrinate in children with vomiting is associated with a risk of delay in the diagnosis of treatable medical conditions. PMID- 1913429 TI - Chlamydia trachomatis cervical infection: prevalence and determinants among women presenting for routine gynecologic examination. AB - OBJECTIVE: To determine the prevalence of and risk indicators for Chlamydia trachomatis cervical infection among women presenting for a periodic medical examination. DESIGN: Prevalence study. SETTING: Centre local de services communautaires (CLSC) Saint-Louis du Parc, Montreal. PATIENTS: All women presenting for a routine gynecologic examination from May 1985 to July 1986. Of the 773 (99%) who agreed to participate 56 were excluded because of inadequate diagnostic tests (34), antibiotic intake in the preceding 6 weeks (19) or loss to follow-up after the initial visit (3). OUTCOME MEASURES: Culture was the diagnostic standard, but rapid diagnostic tests were also used. From the identified cases logistic regression analysis was used to evaluate the following risk indicators: age, place of residence, use of oral contraceptives, sexual partners and frequency, history of sexually transmitted disease (STD) and abnormalities found on genital examination. MAIN RESULTS: Fifty-one of the women were found to have C. trachomatis infection, for a prevalence rate of 7.1%; 32 (63%) were completely asymptomatic. Three independent indicators were found: age of 25 years or less (odds ratio [OR] 3.2, 95% confidence limits [CL] 1.8 and 5.9), cervical erythema, contact bleeding or mucopurulent exudate (OR 2.5, 95% CL 1.4 and 4.5) and residency in the CLSC area (OR 2.3, 95% CL 1.1 and 5.1). A history of STD or vaginitis had a significant protective effect in women 30 years of age or more (OR 0.2). CONCLUSIONS: Case-finding for chlamydial infection could be an effective public health measure among women 25 years of age or less and among those with signs of cervicitis when they present for a Papanicolaou test. PMID- 1913432 TI - Fibrates and HMG-CoA reductase inhibitors. PMID- 1913433 TI - Psychiatry in general practice. 1933. PMID- 1913434 TI - ANA council merger creates council of nurses in advanced practice. PMID- 1913435 TI - Children of divorce: ways to heal the wounds. AB - Each year many children experience the trauma of parental divorce. Although postdivorce responses of children vary considerably in intensity and duration, distinct patterns related to developmental stages have been identified. Latency age and early adolescent children are particularly vulnerable to emotional sequelae, as evidenced by lowered self-esteem, declining sense of social competence, and a higher than usual propensity for substance abuse, depression, and suicide. Individual differences in adjustment are related to personal characteristics, qualities of the home and parenting environment, and resources and support systems available to the child; however, research findings suggest that parental conflict is the most significant predictor of long-term adjustment of children postdivorce. Interventions to reduce parental conflict and assist the child have been identified. The clinical nurse specialist can favorably influence adjustment outcome of children by informing divorcing parents of the potential effects of divorce on children and advocating appropriate interventions. PMID- 1913436 TI - The reciprocal relationship between practice and theory. PMID- 1913437 TI - The eye of the beholder: Parse's theory with homeless individuals. AB - This article describes how practice with homeless persons in a community setting was guided by Parse's theory of nursing. The ways in which Parse's theory differs from the traditional problem-based approach are presented. Parse's practice method as lived with homeless individuals is described as it unfolded in both group sessions and individual encounters. Experiences common to all human beings in day-to-day relating with the world are presented from the perspectives of those who are homeless. Group sessions included discussions about love, pain, beauty, and the choices in life. Encounters with individuals clarify how Parse's theory guided the nurse as the person struggled to move on. Individuals involved with the center offered their perceptions of the way nurses interrelated with them. The evaluation of Parse's theory in various practice settings is proposed, and nurses are challenged to consider this innovative approach for guiding practice with all human beings. PMID- 1913438 TI - The role of a pediatric clinical nurse specialist in a general emergency department. AB - Emergency care of pediatric patients often requires specialized skills not regularly practiced in general emergency departments. Optimally, pediatric patients should be treated in specialized pediatric facilities; however, limited resources often make this impossible. The pediatric clinical nurse specialist practicing in the general emergency department is uniquely well-suited to recognize the physiologic and emotional needs of these patients and ensure that effective and efficient care is delivered in this setting. PMID- 1913439 TI - Measuring relationships. PMID- 1913440 TI - Research utilization among clinical nurse specialists. AB - The purpose of this descriptive study was to explore utilization behavior of clinical nurse specialists (CNSs) relative to research-based information as distinguished from nonresearch-based information. A nontraditional conceptualization of knowledge utilization as encompassing both cognitive and instrumental application was employed. Twenty-four CNSs were interviewed in a field survey. Results indicated that subjects most frequently use findings conceptually; while on occasion, as illustrated in case examples, they reported using research both conceptually and instrumentally. Only half of the subjects, however, could list explicit criteria for evaluation of the applicability of findings to practice. What is most striking in this study's findings is its congruence with results from other research conducted on various, nonnursing populations. PMID- 1913441 TI - Remodeling the image of nursing: a powerful strategy for clinical nurse specialists. PMID- 1913442 TI - The role of the clinical nurse specialist in information systems selection. AB - As computer utilization in the health care industry continues to expand, the role of the nurse in the system selection process increasingly becomes paramount. Information systems are more likely to have a nursing perspective if the nurse who is involved in the information system selection process is a clinical nurse specialist (CNS). Three principles of practice which should be utilized in structuring the role of the CNS in the information system selection process are discussed, along with practical guidelines to assist the CNS in participating effectively. PMID- 1913443 TI - Educating the emotions. PMID- 1913445 TI - Communication: roots within nursing. PMID- 1913444 TI - Strategies to promote positive behavior toward elderly patients. AB - The role of the Gerontological Nurse Specialist, regardless of setting, may be impeded by negative attitudes and behavior of caregivers toward the elderly client. Awareness of the contributing variables can assist the Gerontological Nurse Specialist to identify the need for improved attitude awareness and interactions in the care of the elderly. This article, supported by current literature, reviews common variables associated with negative attitudes and behavior of caregivers toward elders. Strategies including exercises in self awareness, clinical nursing rounds, attending behavior development, role modeling, consultation, and inservice are suggested for the Gerontological Nurse Specialist for initiating change. PMID- 1913446 TI - Developing a nursing staff support group model. AB - A nursing staff is an open system that involves constant interactions with other members, patients, and other systems within the hospital environment on an ongoing basis. These constant interactions can contribute to conflict, ambiguity, stress, and strain in the nursing system. Nursing staff support groups are beginning to emerge as an integral part of the health care system. These nursing staff support groups may assist the nursing staff in managing conflict, ambiguity, stress, and strain. The authors explore and present a proposed nursing staff support group model that focuses on the development of the components, i.e., group stressors, clinician's knowledge base, stressed group and effective group behaviors, the clinician's role and expected group outcomes. PMID- 1913447 TI - Showcasing a profession: getting nursing on the newsstand. AB - Interacting with the media is a method of showcasing the nursing profession. Clinical nurse specialists (CNSs) have a variety of opportunities available for these interactions: appearing on television, participating in a radio program or writing to the media. A survey completed by the authors indicated that CNSs had many media interactions, yet overall, only 17% of all nurses surveyed used writing. This paper begins by discussing where to publish and how to prepare and target the audience. General and specific guidelines for publishing feature articles, health tips, letters to the editor, and other publishing possibilities are presented. PMID- 1913448 TI - Fractionated stereotactic radiation therapy for intracranial tumors. AB - In stereotactic radio surgery, a single, large dose of radiation is delivered to a small, well-defined, stereotactically localized intracranial lesion. In contrast to conventional radiation therapy, in radio surgery no attempt is made to spare normal cells within the target volume by fractionating the tumor dose. In 1987, the authors began a program of fractionated stereotactic radiation therapy for selected tumors involving sensitive brain structures. Their objective was to improve the therapeutic index and study the feasibility of the fractionated technique. Fifteen patients were treated with a multifraction regimen typically consisting of six fractions of 700 cGy each, given on alternate days for 2 weeks (total tumor dose, 4200 cGy). All patients were treated with the dynamic stereotactic radio surgical technique. A head ring ("halo frame") was used for immobilization and setup during radiation treatments. At a median follow up time of 27 months, the symptoms of the majority of the patients improved clinically; this improvement usually occurred within a few weeks after completion of the treatment. The radiologic response was much slower. Currently, only two patients have had complete radiologic disappearance of their lesions; the majority of the patients have only had a decrease in tumor size. The treatments were well tolerated by the patients and no acute complications were observed. One patient who had a vasogenic edema 11 months after treatment fully recovered after steroid therapy. Fractionated stereotactic radiation therapy is a feasible treatment technique and may prove to be useful for selected patients with intracranial tumors. Although the preliminary data are encouraging, this technique should still be considered experimental. A larger number of patients and a longer follow-up time are necessary to determine whether the results of this technique are actually better than those of conventional radiation therapy. PMID- 1913449 TI - Chemotherapy for recurrent or metastatic carcinoma of the nasopharynx. A review of the Princess Margaret Hospital experience. AB - There is little information about the ability of chemotherapy to achieve palliation for patients with recurrent or metastatic carcinoma of the nasopharynx. Therefore, the authors reviewed the records of all patients who had received chemotherapy for this disease at the Princess Margaret Hospital between 1970 and 1989. Seventy patients were identified who had measurable disease and had not received prior systemic therapy. Forty patients received single agents or nonaggressive drug combinations, most of them before 1980. There were three complete responses (CR) and seven partial responses (PR) among this group for a response rate of 25% (95% confidence limits, 13% to 41%). Thirty patients received either drug combinations that were active in aggressive lymphomas or cisplatin-based combinations. There were 7 CR and 14 PR among this group for a response rate of 70% (95% confidence limits, 51% to 85%). Two patients who were treated aggressively are still alive and in complete remission at 3 and 12 years. This type of retrospective review cannot exclude bias caused by patient selection. However, in the absence of randomized trials, the authors suggest the following: (1) carcinoma of the nasopharynx should be considered a malignant neoplasm that is distinct from squamous cell cancer in other sites of the head and neck; and (2) selected patients with recurrent or metastatic carcinoma of the nasopharynx should receive aggressive combination chemotherapy. PMID- 1913450 TI - A phase II study alternating alpha-2a-interferon and gamma-interferon therapy in patients with chronic myelogenous leukemia. AB - Patients with Philadelphia chromosome-positive chronic myelogenous leukemia (CML) were treated with a combination of alpha-interferon and gamma-interferon. Recombinant alpha-2a-interferon (Roferon-A, Hoffmann-LaRoche, Inc., Nutley, NJ) and recombinant gamma-interferon (Genentech, Inc., South San Francisco, CA) were administered on alternating weeks each at doses ranging from 2 to 10 MU/m2 given intramuscularly. Of the 27 patients, 11 (41%) achieved complete hematologic remission (CHR) and 3 (11%) achieved partial hematologic remission (PHR). Responses were seen among 9 of 22 (41%) patients treated during the chronic phase of the disease and in 2 of 5 (40%) patients treated during the accelerated phase/second chronic phase. Cytogenetic responses were seen in six patients, including one complete response and five minor responses. Toxicities included flu like symptoms, which appeared to be more severe with gamma-interferon than with alpha-interferon, hypertriglyceridemia, and thrombocytopenia. In this limited study, an improved outcome was not observed for the combination regimen compared with alpha-interferon alone. PMID- 1913451 TI - Basal cell carcinoma treated with radiation therapy. AB - Between 1974 and 1989, 85 patients with 115 biopsy-proven basal cell carcinomas were treated with radiation therapy at the University Medical Center in Tucson. Either orthovoltage or megavoltage photons were used to deliver doses ranging from 2000 cGy in a single treatment to 7300 cGy in 35 fractions over 62 days. The median length of follow-up was 40 months. Kaplan-Meier estimates of the 5-year local control rates are presented by American Joint Committee on Cancer stage. The difference between the local control rates for both previously untreated and recurrent Stage I and II carcinomas (95% at 5 years) and Stage III and IV carcinomas (56% at 5 years) was statistically significant (P = 0.0001, by Mantel Haensel test). Although recurrent basal cell carcinomas generally have a worse prognosis, the Kaplan-Meier estimate of the 5-year local control rate for recurrent Stage I and II carcinomas treated with radiation therapy was 95%. These results, along with a review of the literature, suggest two points: (1) high cure rates can be obtained when Stage I and II basal cell carcinomas are treated with radiation therapy and (2) radiation therapy is a relatively effective method for treating recurrent basal cell carcinomas, with cure rates surpassed only by Mohs micrographic surgery. PMID- 1913452 TI - Incidence of radiation myelitis of the cervical spinal cord at doses of 5500 cGy or greater. AB - The incidence of permanent damage to the spinal cord as a complication of radiation therapy generally correlates positively with total radiation dose. However, several reports have indicated that fraction size is also an important factor in the development of late damage in normal tissue. To determine the effect of fraction size on the incidence of radiation-induced spinal cord damage, the authors reviewed 176 cases of head and neck cancer treated at their department between 1980 and 1990 with radiation doses of 5500 cGy or greater to a portion of the cervical spinal cord. Majority of these patients received 6000 cGy or greater with fraction size ranging from 150 to 200 cGy. Seventy-two of 176 patients have been observed for 2 years or more. More than one third (26 patients) of these received greater than 6000 cGy with fraction sizes of 157 to 170 cGy. Four of 72 (5.6%) patients had experienced permanent cervical spinal cord damage. The results of this study suggest that radiation damage to the cervical spinal cord correlates not only with total radiation dose, but also with fraction size. Low fraction sizes appear to decrease the incidence of such damage. PMID- 1913453 TI - Relationship among outcome, stage of disease, and histologic grade for 22,616 cases of breast cancer. The basis for a prognostic index. AB - Survival rates for 22,616 cases of breast cancer listed in the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute were stratified on outcome according to the histologic grade and stage of disease. Two different staging systems, "local, regional, and distant" and a modified American Joint Committee on Cancer (AJCC) system adopted for SEER were used. Relative survival rates were calculated at 5 and 10 years. Patients who were assigned Stage II, Grade 1 had the same survival as those assigned Stage I, Grade 3. Their survival was better than patients assigned Stage I, Grade 4. The 5 year relative survival rate for patients listed as Stage I, Grade 1 was 99% and for patients listed as Stage I, Grade 2, it was 98%. At 10 years, the survival rate of patients assigned Stage I, Grade 1 was 95%. Patients with histologic Grade 1 tumors less than 2 cm in size and with positive axillary lymph nodes had a 5-year survival rate of 99%. As breast tumors increased in size, the histologic grade also increased. The results suggest that in linking histologic grade with stage of disease, the staging system should also be considered. Histologic grade when used in conjunction with stage of disease can improve the prediction of outcome. Our results also indicate that a prognostic index can be created for breast cancer using a combination of stage of disease and histologic grade. The data suggest that only three grades are needed for breast cancer. PMID- 1913454 TI - Surface marker analysis and karyotype distinguish acute biphenotypic leukemia from acute myelogenous leukemia expressing terminal deoxynucleotidyl transferase. AB - Surface phenotyping by flow cytometry and cytochemical study were used to identify 15 adult patients with acute leukemia displaying ambiguous phenotypes. Differences were found in the blast cell karyotype and immunoglobulin gene rearrangements of terminal deoxynucleotidyl transferase (TdT)-positive acute myelogenous leukemia (AML) and biphenotypic leukemia expressing B lymphoid and myeloid markers. The karyotypic abnormalities, t(9;22) and t(4;11), were noticed in acute biphenotypic leukemia, and were consistently associated with rearrangement at the immunoglobulin locus. Furthermore, coexpression of CD19/CD20 and either myeloperoxidase or myeloid surface markers were predictive of finding the t(9;22) or t(4;11) karyotype. Patients with TdT-positive AML, on the other hand, were less likely to show rearrangement at the immunoglobulin locus, and did not have the t(9;22) or t(4;11). Instead, a variety of nonrandom karyotypic abnormalities were seen, including trisomy 13. Unlike common AML, the majority of TdT-positive cases demonstrated an abnormal karyotype with duplications and/or deletions present in all cases. In no instance was trisomy 8, t(8;21), t(15;17), or any other isolated translocation identified. The authors therefore suggest that immunophenotyping, when combined with cytochemical analysis of TdT and myeloperoxidase or Sudan black B, may aid in the characterization of subgroups of atypical acute leukemia, such that alternate approaches to therapy can be evaluated. PMID- 1913456 TI - Flow cytometric quantitation of the proliferation-associated nuclear antigen p105 and DNA content in advanced gastric cancers. AB - Flow cytometric quantitation of the proliferation-associated nuclear antigen p105 was done on cancer cell suspensions from 114 advanced gastric cancers and correlated with clinical behavior. DNA diploidy was observed in 45 (39.5%) and aneuploidy in 69 (60.5%) cases. By setting the cutoff line at the level used in a negative control study without primary antibody in the same sample, the p105 labeling rate was calculated by the p105-DNA dual fluorescence analysis. The mean p105-labeling rate was 37.7% (range, 9.3% to 79.0%). The p105-labeling rates were significantly higher (P less than 0.05) for aneuploid DNA, liver metastasis, vascular invasion, and histologically well-differentiated tumors. The 5-year survival rate of patients with high p105-labeling tumors (p105-labeling rate, greater than 30%) was significantly poorer (P less than 0.01) than that of patients with low-labeling tumors. When the p105-labeling rate and the clinicopathologic parameters were entered simultaneously into the Cox regression model, the stage of disease, DNA ploidy, p105-labeling rate, and vascular invasion emerged as independent prognostic parameters. These findings indicate that the measurement of p105 may provide useful information for predicting prognosis in advanced gastric cancers. PMID- 1913455 TI - An ultrastructural study of in vivo interactions between lymphocytes and endothelial cells in the pathogenesis of the vascular leak syndrome induced by interleukin-2. AB - Lymphokine-activated killer (LAK) cells play a major role in the induction of the vascular leak syndrome (VLS). To understand the mechanism of this syndrome, the authors examined light and electron microscopic alterations in the lung, liver, spleen, kidney, and heart of mice in which VLS was produced by the administration of interleukin-2 (IL-2) (seven injections of 600,000 IU each for a period of 4 days). The results of these studies disclosed that considerable damage had been done to the endothelial cells that consisted of cytoplasmic edema, vacuoles, and myelin figures; in addition, there were frequent sites of transendothelial passage of lymphoid cells, probably IL-2-activated cells, that penetrated through their cytoplasm by means of "temporary migration pores" and accumulated in the perivascular spaces. The results of this study indicate that a direct in vivo interaction between IL-2-activated cells (probably LAK cells) and endothelium results in cytotoxicity to endothelial cells. PMID- 1913457 TI - A clinicopathologic and immunomorphologic study of 13 cases of ganglioglioma. AB - The authors present the clinical, histopathologic, and immunomorphologic data of 13 intracranial gangliogliomas. Preoperative computed tomography scans showed a commonly cystic tumor of variable density. Six tumors were completely excised and seven were subtotally resected. After a mean follow-up of 4.5 +/- 2.6 years, 11 patients are asymptomatic or only slightly incapacitated. All tumors were examined with a panel of neuronal and neuroendocrine markers. Immunoreactivity (IR) to anti-neurofilament polypeptide (clone 2F11) was observed in neuronal processes in ten cases and in neuronal perikarya in five. With anti-synaptophysin (clone SY38), IR was present along the lining of ganglion cell perikarya and processes in 11 tumors whereas staining of the perinuclear cytoplasm was prominent in two. IR to anti-chromogranin A (clone LK2H10) was observed within the neuronal perikarya in eight cases. Only one ganglioglioma of the brain stem showed IR for tyrosine-hydroxylase (clone 2/40/15) and dopamine-beta-hydroxylase in some neoplastic ganglion cells. In this study, synaptophysin was the most reliable neuronal marker. For immunocytochemical identification of neoplastic neurons in ganglioglioma as well as other tumors with neuronal differentiation the authors propose a panel of well-characterized monoclonal antibodies against neurofilament polypeptides, synaptophysin, and chromogranin A to support the histomorphologic diagnoses. PMID- 1913458 TI - Heterogeneity in the gingival fibromatoses. AB - Forty-nine cases of isolated familial and idiopathic gingival fibromatoses, consisting of 12 cases from six families and 37 cases of idiopathic gingival fibromatosis, were reviewed. Pedigrees of five families revealed various penetrances and genetic heterogeneity as suggested by the presence of both autosomal dominant and autosomal recessive inheritances. Ultrastructurally, the lesions were composed of fibroblast-like cells and myofibroblast-like cells, with the former being the predominant cell type. The 267 cases of familial and idiopathic gingival fibromatoses were analyzed, and they with or without hypertrichosis, mental retardation, and/or epilepsy. These included 49 cases seen by the authors, 50 cases from the Japanese literature, and 168 cases from non Japanese literature. Isolated gingival fibromatosis occurred more frequently after age of 12 years (P less than 0.0074). There was no significant difference in age of onset between generalized and localized forms of the idiopathic gingival fibromatosis. Gingival fibromatosis with hypertrichosis and mental retardation and/or epilepsy occurred frequently before 12 years (P less than 0.069). It has been shown that heterogeneity of the gingival fibromatosis is a result of either histologic heterogeneity, genetic heterogeneity, or a combination with other systemic disorders. PMID- 1913459 TI - Prognostic value of Rhesus blood groups in oral squamous cell carcinomas. AB - In the current study of the prognosis of all patients (N equals 70) with squamous cell carcinomas (SCC) of floor of mouth in Norway during the period 1963 to 1972, the authors found that patients with Rhesus (Rh) (D)-negative blood group had significantly poorer prognosis (mean 5-year survival, 8%) than patients with Rh (D)-positive blood group (5-year survival, 30%) (P equals 0.04). This extends the authors' previous observations in another group of oral cancer patients. The authors do not know the explanation for this association. However, the Rh gene locus is located on the short arm of chromosome 1 which reportedly has shown rearrangements in some head and neck SCC and other human neoplasms. The authors therefore speculate that the Rh gene locus may be linked with chromosome 1 changes of importance for the progression of oral SCC. PMID- 1913460 TI - Polycythemia and steroid overproduction in a gonadotropin-secreting seminoma of the testis. AB - While investigating the cause of mild polycythemia in a young man, a testicular seminoma was discovered with unusual and tumor-dependent features: an absolute polycythemia with high plasma erythropoietin (EPO) levels, an overproduction of estradiol and testosterone, and a dramatic Leydig cell hyperplasia surrounding the tumor tissue. The authors attempted to gain insight into the relationship between this testicular tumor and the hormonal overproduction, i.e., of EPO, estradiol, and testosterone. Their results favored the conclusion that the high EPO levels and the polycythemia were an indirect effect secondary to the steroid overproduction rather than a direct EPO-producing activity. Moreover, the steroid overproduction by the testis could be caused by a paracrine mechanism through human chorionic gonadotropin activity on the Leydig cells. PMID- 1913461 TI - Histologic, biochemical, and clinical parameters for monitoring multiple myeloma. AB - In a retrospective and prospective follow-up study from 1968 to 1989, bone marrow biopsy specimens, serum beta-2-microglobulin (SB2M) levels, and the clinical features of 251 patients with multiple myeloma (MM) and 28 patients with monoclonal gammopathy of undetermined significance (MGUS) were investigated. The main histologic variables (tumor cell type, tumor growth, tumor load, and fibrosis), SB2M level, serum thymidine kinase (STK) level, and various clinical parameters were analyzed to determine factors of value in monitoring the clinical phases of activity in MM. Our recently proposed prognostic strategy combining bone marrow histologic type, SB2M level, and signs of organ failure was tested for its ability to (1) diagnose the early and smoldering variants; (2) facilitate decisions on the time of initiation, the type and duration of initial induction therapy in the pretreatment phases (active and rapidly progressive phases); and (3) characterize variations in tumor regression and tumor-host interactions during chemotherapy (early treatment, plateau, relapse, transition, and refractory phases). The results indicate that this clinicopathologic monitoring combines information both on stage and aggressivity of MM and thus facilitates therapeutic decisions in the various clinical phases of MM. PMID- 1913462 TI - Electrical taste detection thresholds and chemical smell detection thresholds in patients with cancer. AB - Taste sensation in patients with cancer has previously been studied with the cumbersome method of chemical gustometry, which have produced inconsistent results. In this study taste thresholds were determined with the simple and reliable technique of electrogustometry in 51 patients with cancers of the lung (small cell), ovary or breast, and in 29 matched control patients with nonneoplastic disease. Chemical smell thresholds for phenyl-methyl-ethyl-carbinol were studied in the same group of patients. Electrical taste threshold was higher in patients with cancer compared with control patients (30 [12 to 80] microA versus 9.5 [6.1 to 24] microA; median [interquartile range], P less than 0.001). No differences were seen in smell thresholds. Patients who responded to chemotherapy obtained a decreased electrogustometric threshold at time of reevaluation (24 [8 to 64] microA versus 30 [15 to 90] microA; median [interquartile range], P less than 0.05). These results suggest an effect of the malignant disease itself on taste thresholds. PMID- 1913463 TI - Leukemic dermal infiltrates at permanent indwelling central venous catheter insertion sites. AB - Three cases of leukemic dermal infiltrates at permanent indwelling central venous catheter insertion sites in patients with acute myelogenous leukemia are reported. Two patients had a localized soft tissue mass at the previous permanent indwelling catheter insertion site as the sole initial manifestation of relapse after achieving complete remission and undergoing bone marrow transplantation. The third patient had catheter tunnel sepsis preceding leukemic dermal infiltration. A review of the English language literature showed that this condition is rare with no specific pathogenetic mechanisms identified. Patients with unresolved catheter tunnel infections in acute leukemia and persistent chest wall masses that appear after a previous permanent indwelling catheter should have a biopsy done and be treated promptly. PMID- 1913464 TI - Primary lymphoma of the heart. Prolonged survival with early systemic therapy in a patient. AB - Primary lymphoma of the heart is an uncommon malignancy usually recognized at autopsy or fatal within a few weeks of diagnosis. Recently, it was reported in patients with acquired immune deficiency syndrome. A patient with diffuse large cell lymphoma of the heart is reported who had chest pain and rapidly evolving cardiac arrhythmias. The human immune deficiency virus antibody test was negative. Because of an aggressive diagnostic approach, therapy with cyclophosphamide, doxorubicin, vincristine, and prednisone was started on the third day after diagnosis. The patient has survived 18 months with an objective response. To the authors' knowledge, this is the longest reported survival in primary cardiac lymphoma. The diagnosis in this patient was aided by excellent tumor delineation by nuclear magnetic resonance scanning. The authors believe that better survival in this patient was a result of prompt diagnosis and treatment because the behavior of the lymphoma was similar to aggressive lymphomas arising elsewhere. PMID- 1913465 TI - The significance of squamous differentiation in endometrial carcinoma. Data from a Gynecologic Oncology Group study. AB - Squamous differentiation is identified in about 25% of endometrial adenocarcinomas (AC). Its significance has been the subject of debate for decades, and it has been reported that the prognosis of adenoacanthoma (AA) is better than, the same as, and worse than that of AC. Part of this confusion has resulted from semantic differences relating to the use of AA and adenosquamous carcinoma (AS). To investigate the prognostic importance of squamous differentiation in endometrial carcinomas and compare the prognostic utility of two classification systems, 456 women were studied who had typical AC and 175 women who had typical AC containing areas of squamous differentiation (AC + SQ) and who had been entered in a Gynecologic Oncology Group protocol of Stage I and II endometrial adenocarcinoma. Assessment of histologic grade and depth of invasion was done both by the pathologist at the member institution and at a second highly structured review. Differentiation of the squamous component of endometrial carcinomas was found to parallel that of the glandular component in most tumors. The biologic behavior of endometrial carcinomas with squamous elements was similar, but not identical, to that of typical AC. Although the frequency of nodal metastasis was similar for both AC and AC + SQ, the presence of squamous elements was associated with an increased probability of survival. Division of AC + SQ by depth of myometrial invasion and by architectural grade of the glandular component provided useful prognostic information that was superior to that resulting simply from division of AC + SQ into AA or AS. The authors recommend that these terms be replaced by "adenocarcinoma with squamous differentiation" and that the pathologist provide information on the architectural grade and depth of myometrial invasion to guide the gynecologist in determining appropriate therapy. PMID- 1913466 TI - Evaluation of the reproducibility of the revised 1988 International Federation of Gynecology and Obstetrics grading system of endometrial cancers with special emphasis on nuclear grading. AB - An intraobserver and interobserver analysis of the reproducibility of the revised 1988 International Federation of Gynecology and Obstetrics (FIGO) grading system of endometrial cancers was performed in 47 endometrial cancers (94 biopsy specimens). In the revised FIGO grading system the growth pattern still serves as the basic parameter, but nuclear atypia inappropriate for the architectural grade, raises the grade by 1. Ninety-four slides were graded twice by two pathologists. Analysis by the kappa statistics (corrected for agreement by chance) showed an acceptable result for interobserver reproducibility: kappa value 0.65 (95% confidence interval, 0.480 to 0.818). Further study showed this to be a reflection of the reproducibility of the architectural grade: kappa 0.70 (95% confidence interval, 0.565 to 0.850), whereas the reproducibility of the nuclear grade was poor: kappa value 0.55 (95% confidence interval, 0.383 to 0.713). Review of the literature showed great variability in the definition of nuclear grading, indicating that the revised 1988 FIGO grading system is not applicable as standard of reference for studies of endometrial cancers, before agreeing to the definition of inappropriate nuclear atypia. PMID- 1913467 TI - An atypical myeloproliferative disorder with high thrombotic risk and slow disease progression. AB - Among 761 consecutive patients with chronic myeloproliferative disorders (CMD), it was found that 18 (nine men and nine women) did not fulfill at presentation the established diagnostic criteria for the typical forms. In seven patients, the diagnosis of CMD was made on the basis of an intense and persistent thrombocytosis that complicated splenectomy. The other 11 patients had various combinations of the following signs suggesting CMD: splenomegaly, bone marrow myeloid hyperplasia and/or slight myelofibrosis, mild thrombocytosis and/or leukocytosis, and rare immature myeloid cells in the peripheral blood. All patients were younger than 46 years of age (median age, 31.5 years; range, 20 to 45 years). A major thrombotic event was the most frequent presenting feature (eight of 18 cases), and thrombotic complications supervened in seven of the eight splenectomized patients (six in the portal system), raising the overall rate of patients with thrombotic events in their history to 11 of 18. At a median follow-up of 50 months (range, 24 to 241 months), three patients had died of thrombotic complications (two after splenectomy). The 15 surviving patients had stable disease, and 12 of them were not receiving cytoreductive therapy. Spontaneous growth of circulating burst-forming units erythroid was demonstrated in one patient, and erythroid responsiveness to erythropoietin appeared higher than in the normal controls in four. Spontaneous in vitro platelet aggregation in whole blood and/or platelet-rich plasma was seen in five of seven patients. It was concluded that a difficult to identify, slowly progressive form of CMD occurs in young people, that it carries a high risk of thrombosis, and that splenectomy is a high risk procedure in these cases. PMID- 1913468 TI - Malignant angioendotheliomatosis presenting as disseminated intravascular coagulopathy. AB - Disseminated intravascular coagulopathy (DIC) occurred in a patient with hemolytic anemia and anasarca. Skin and muscle biopsy showed intravascular lymphomatosis (malignant angioendotheliomatosis). Combination chemotherapy resulted in resolution of the DIC and anasarca. After an unmaintained 8-month clinical remission, the patient had central nervous system relapse and died. Malignant angioendotheliomatosis is a rare disorder that should be considered among the occult causes of DIC. PMID- 1913469 TI - Treatment of malignant Leydig cell tumor. AB - Malignant Leydig cell tumors (LCT) are rare. Only 32 cases of malignant LCT (as evidenced by metastatic spread) were reported. Generally metastatic spread occurs within 2 years of the primary LCT, and the patient dies within 2 years of the discovery of metastatic disease. The tumor is highly resistant to both radiation and chemotherapy. It also has a great propensity for recurring after surgical resection. A case is reported of a patient whose metastatic disease occurred 8 years after his primary LCT had been resected. He was treated with doxorubicin and mitotane without response. The clinical features of this case are highlighted, and a review of the literature describing treatment of this rare disease is presented. PMID- 1913470 TI - The coexistence of lymphangiosarcoma and Kaposi's sarcoma in a renal transplant recipient. AB - A case of coexisting lymphangiosarcoma and Kaposi's sarcoma that occurred in a female renal transplant recipient is presented. Both sarcomas were localized to the skin and were slowly progressive over several years. The coexistence of these two sarcomas may indicate that they arose from a common precursor endothelial cell and that systemic immune suppression may be important in the pathogenesis of both these malignancies. PMID- 1913472 TI - Magnetic resonance imaging of neurohypophyseal germinomas. AB - The authors reviewed magnetic resonance (MR) images in seven cases of germinoma in the hypothalamoneurohypophyseal axis (HNA). The intrasellar portions were clearly identified in six germinomas. Two small germinomas of these six were located only in the neurohypophysis. The major parts of the four large germinomas were located below the optic chiasm, and the large intrasellar portions were demonstrated. The remaining one small germinoma was localized from the pituitary stalk to the third ventricular floor. These findings strongly suggest that the primary site of germinomas in the HNA is the neurohypophysis. In the four large germinomas, the tumor shape was similar to that of pituitary adenoma. The authors believe that age (limited to first three decades), symptoms (diabetes insipidus), MR findings (absence of normal hyperintense signal of the posterior pituitary on T1-weighted (T1WI) images, and homogeneous hypointensity to the pons on T1WI images/isointensity on T2-weighted images are important in differential diagnosis. PMID- 1913471 TI - Merkel cell carcinoma. Improved locoregional control with postoperative radiation therapy. AB - Between April 1981 and May 1990, 11 patients with Merkel cell carcinoma were treated with radiation therapy in Tucson, Arizona. The length of follow-up time from the time of irradiation ranged from 6 to 64 months. Locoregional control was maintained in seven of eight patients treated with surgery and postoperative radiation therapy for primary or recurrent cancer. The other three patients had bulky metastatic disease at the time of referral. Palliation was achieved in all three patients with radiation therapy. Hyperthermia also appeared to be beneficial in the one patient in which it was used, and chemotherapy achieved responses in two of four patients. These results, combined with a review of the literature, suggest that the administration of radiation therapy postoperatively to both the surgical bed and the draining lymph nodes improves locoregional control and may result in long-term disease-free survival when administered after the initial surgical resection. PMID- 1913473 TI - Subxiphoid partial pericardiectomy with or without sclerosant instillation in the treatment of symptomatic pericardial effusions in patients with malignancy. AB - Twenty-two patients with malignant pericardial effusions were treated with subxiphoid partial pericardiectomy between 1984 and 1989. Thirteen patients also had a sclerosing agent instilled intrapericardially. Tamponade was relieved by pericardiocentesis before administration of general anesthesia. In 18 patients (82%), the effusions were controlled for longer than 30 days, and two patients died before 30 days without effusion. There were two recurrences at 1.5 and 7 months. There was one death due to hemorrhage from a laceration in a heavily infiltrated pericardium, and one patient had persistent dyspnea after the procedure. Complications included transient atrial arrhythmias (two patients), chest pain after sclerosant instillation (three patients), and fever greater than 37.5 degrees C after sclerosant (five patients). The survival range was 0.1 to 18 months (median, 5 months). Subxiphoid partial pericardiectomy with or without intrapericardial sclerosant is a safe and efficacious treatment for malignant pericardial effusions. PMID- 1913474 TI - Sigma S, a measure of reactive sulfur groups of immunoglobulin G, is a sensitive tumor marker discriminating different stages of breast cancer. AB - Sigma S is a measure of the disulfide bonds and free thiol groups of serum immunoglobulin (Ig) G, as determined by the reaction with dithionitrobenzoate. Significant decreases of sigma S previously were detected in malignant compared with benign diseases of various organs. This study shows the application of sigma S for the diagnosis of breast cancer. The following results were obtained. First, 132 patients with benign breast diseases showed a sigma S of 1.48 +/- 0.29 (standard deviation) per mole IgG; this was not different from 1.51 +/- 0.36 found in 182 controls. In contrast, IgG from 198 patients with primary breast carcinoma of all four stages (tumor-node-metastasis system) gave a sigma S of 1.22 +/- 0.29, a significant (P less than 0.0001) decrease of sigma S from benign to malignant breast disease. Second, sigma S values of single Stages I, II, III, and IV, were 1.27 (n = 59), 1.23 (n = 83), 1.19 (n = 35), and 1.10 (n = 21), respectively, each significantly different from sigma S in benign disease and showing a decreasing trend with increasing tumor progress. Differences were significant between Stages I and IV (P less than 0.025) and II and IV (P less than 0.05). Third, 63% of Stage I breast carcinoma patients had sigma S values below a critical threshold of 1.38. This serum positivity rose to 90% in Stage IV. These values exceeded those reported with other tumor markers. The overall power of sigma S to distinguish between benign and malignant breast disease had a specificity of 61% and a sensitivity of 78%. Early stages (I and II) of breast cancer could be distinguished from benign diseases with 64% specificity and 69% sensitivity. Advanced Stage IV could be discriminated from early Stages I and II with 55% specificity and 71% sensitivity. Thus, the analysis of sigma S may significantly contribute to the surveillance of patients with breast cancer. PMID- 1913475 TI - Malignant histiocytosis X. A distinct clinicopathologic entity. AB - Histiocytosis X (HX) is characterized morphologically by a proliferation of Langerhans' cells (LC), and most often has an indolent, chronic course. To determine whether a distinct clinicopathologic entity of malignant histiocytosis X exists, the authors examined tissues from 31 patients with HX and divided them into four categories. Group A (19 patients) was characterized morphologically by benign-appearing LC and had an indolent course. The male:female (M:F) ratio was 10:9, and the mean age was 21 years (range, 2 months to 60 years). The immunophenotype of this group was S-100+, vimentin+, LN-2+, LN-3+, lysozyme-, LCA , Leu-M1-. Group B (three patients) had benign-appearing LC, yet had an aggressive clinical course. All patients were male, with a mean age of 47 years (range, 3 years to 72 years). Organs involved included the liver, spleen, heart, thymus, lung, kidney, and pancreas. The immunophenotype was the same as for Group A. Group C (two patients) had atypical and malignant appearing LC, yet a relatively benign clinical course. The ages were four and 65 years, with one female and one male patient. In both patients, the cells were S-100+, vimentin+, LN-2+, LN-3+, and LCA-. Group D (seven patients) was characterized by atypical and malignant-appearing LC and an aggressive clinical course. The mean age was 25 years (range, congenital to 54 years) with one female and six male patients. Organs involved were the thymus, lungs, spleen, liver, kidney, brain, heart, pancreas, stomach, and muscle. Birbeck granules were found in two patients, and the one patient on which fresh tissue was available was CD1+. The typical immunophenotype was S-100+, vimentin+, LN-2+, LN-3+, Leu-M1-, lysozyme-. The results of our study indicate that (1) a distinct clinical entity of malignant HX, characterized morphologically by malignant-appearing LC and clinically by male predominance, atypical organ involvement, and an aggressive clinical course, does exist; and (2) the morphologic appearance of the LC is an imperfect predictor of the clinical severity of HX. PMID- 1913476 TI - Coexisting macrophage-associated fibrin formation and tumor cell urokinase in squamous cell and adenocarcinoma of the lung tissues. AB - Mechanisms of coagulation activation in situ were studied by means of immunohistochemical techniques applied to surgically resected primary adenocarcinomas and squamous cell carcinomas of the lung. Findings in these two histologic types were similar. Double-labeling techniques using macrophage specific antibody together with antibody to either tissue factor, factor VII, factor X, or factor V revealed coincident staining for each of these coagulation factors on tumor-associated macrophages. Staining of tumor cells for these factors was rare and inconsistent. Both macrophages and fibroblasts in the tumor connective tissue stained for the a subunit of factor XIII. Fibrinogen was abundant throughout the tumor connective tissue, but staining for fibrin and D dimer cross-linked sites of fibrin was restricted to areas adjacent to macrophages, indicating that thrombin was generated in association with tumor macrophages but not with tumor cells. By contrast, tumor cells stained diffusely for urokinase-type plasminogen activator and focally for thrombomodulin. These findings contrast with those reported previously for small cell carcinoma of the lung and suggest that coagulation activation in adenocarcinoma and squamous cell carcinoma of the lung may occur indirectly through activation of certain host cells such as macrophages. By contrast, tumor cell plasminogen activator may mediate certain aspects of the malignant phenotype in these tumor types. PMID- 1913477 TI - Near diploid large bowel carcinomas have better five-year survival than aneuploid ones. AB - One hundred patients who underwent surgery for large bowel carcinoma between 1978 and 1982 were examined by flow cytometric DNA quantitation of fresh tumor specimens and divided into an aneuploid (AN) group of 63 and a near diploid (ND) one of 37. All patients were followed until death (n = 63) or until December 31, 1988. Forty-one patients (65%) with AN tumors died of cancer, as did 12 patients (32%) with ND carcinomas. Thus patients with ND tumors had a better survival rate (P = 0.04) than did those with AN ones. The difference was apparent in Dukes' Stages A, B, and C, but not in Stage D. All patients with tumors in this stage died from their carcinomas irrespective of ploidy group. Multiple regression analyses (Cox) of prognostic factors revealed that the most important prognostic variables were (in descending order) Dukes' Stage D, Dukes' Stage C, and DNA ploidy pattern. Histologic grade was not significant as an independent prognostic variable. These results indicate that the presence of a distinctly aneuploid DNA ploidy pattern in large bowel carcinoma is an important prognostic variable that worsens survival rates significantly. PMID- 1913478 TI - Retroperitoneal neurilemoma presenting with humoral hypercalcemia associated with markedly elevated plasma prostaglandin levels. AB - A 72-year-old woman complaining of somnolence and thirst was diagnosed to have a hypercalcemic crisis (corrected serum calcium level, 17.4 mg/dl) associated with encephalopathy and nephropathy. Imaging diagnostic techniques demonstrated a retroperitoneal tumor at the median site of right renal pelvis. Hormonal studies revealed that plasma levels of thromboxane B2, prostaglandin (PG) E2, 6-keto prostaglandin F1 alpha (PGF1 alpha) and prostaglandin F2 alpha (PGF2 alpha) were markedly elevated. The tumor was successfully removed by operation; her serum calcium level and PG levels normalized without any treatment indicating that this case belongs to the category of humoral hypercalcemia of malignancy (HHM). Pathologically, this tumor was diagnosed to be a benign neurilemoma. Parathyroid hormone-related protein (PTHrP) radioimmunoassay and Northern blot hybridization for PTHrP mRNA were negative. The current case demonstrates that hypercalcemic crisis could be induced by a curable benign neurilemoma, and suggests that this HHM-like morbidity was associated with markedly elevated plasma PG levels. PMID- 1913479 TI - Hyperphosphatemia in multiple myeloma due to a phosphate-binding immunoglobulin. AB - Hyperphosphatemia (HP) is usually seen in patients with hypoparathyroidism, renal failure, and tumor lysis. The authors described a patient with HP due to a phosphate-binding immunoglobulin (Ig). An 86-year-old woman had serum phosphate levels as high as 4.75 mmol/l, (normal, 0.77 to 1.45 mmol/l). Serum ionized calcium, blood urea nitrogen (BUN), creatinine, and N-terminal parathyroid hormone (PTH) levels were normal, but serum 1,25-dihydroxyvitamin D level was subnormal at less than 12 pmol/l (normal, 36 to 146 pmol/l). Serum total protein was elevated at 105 g/l (normal, 60 to 80 g/l), and additional studies confirmed a diagnosis of immunoglobulin G (IgG) multiple myeloma. Results of in vitro studies using anti-human IgG antibodies showed that the IgG of the patient bound inorganic phosphate. Several isolated case reports have documented spurious HP due to interference of the paraprotein in the routine serum phosphate assay. In only one patient, however, has actual binding of phosphate to a myeloma protein been documented. The studies of the authors document phosphate binding by an IgG paraprotein and suggest that in this setting HP may be of physiologic significance as evidenced by depressed serum levels of 1,25-dihydroxyvitamin D. PMID- 1913480 TI - Prognostic significance of DNA cytometry in cutaneous malignant lymphomas. AB - The current classification of cutaneous malignant lymphomas (ML) into low-grade and high-grade lymphomas was found to be of limited reproducibility and permitted only a rough prediction about outcome. With this in mind, the relationship between nuclear DNA content and both prognosis and histologic grading according to the Kiel classification was evaluated on Feulgen-stained imprint specimens. In all, 49 cases of malignant non-Hodgkin's lymphoma, primary of the skin or with an involvement of the skin as one of the first symptoms, were studied using a computerized high-resolution image analysis system. The 2c deviation index (2cDI), which reflects the variation of the nuclear DNA values around the normal diploid peak, was found to be the best prognostically relevant criterion. Using the 2cDI, a significant discrimination (P less than 0.001 in the U test) between low-grade and high-grade ML was achieved. The prognostic benefit of the 2cDI was well documented by a significant inverse correlation between the 2cDI and the period of time until the patients progressed at least into one higher stage or died of lymphoma (r equals -0.63, P less than 0.05). In addition, the 2cDI enabled prognosis of the course of disease. In the group with low 2cDI values (2cDI, less than 0.5), no progression of the disease was observed after 1 year. In the groups presenting with a 2cDI between 0.5 and 1.0 and higher than 1.0, a progression was found in 57% and 64% of the cases studied, respectively. In conclusion, these measurements indicate that the determination of DNA distribution patterns in imprint specimens allows a precise and objective prognostic evaluation of cutaneous ML. PMID- 1913481 TI - A case of adenocarcinoma of the lung associated with a neck mass and hypercalcemia. AB - The case of hypercalcemia secondary to metastasis to a benign parathyroid adenoma is reported. The patient had documented lung adenocarcinoma with multiple bone metastases and a mass in the lower anterior neck for at least 5 months before hypercalcemia and hypophosphatemia resistant to treatment developed. Autopsy revealed widespread metastatic disease including metastatic tumor invading a benign parathyroid adenoma. The analysis of four cases of metastatic cancer spread to a benign parathyroid adenoma reported previously revealed that two of them also had hypercalcemia during a late stage of the disease. There are data that the incidence of metastases to parathyroid gland might be as high as 11.9%, and the incidence of parathyroid adenomas in patients with cancer is significantly higher than in controls. The metastases to benign parathyroid adenomas might be another mechanism of hypercalcemia of malignancy. PMID- 1913482 TI - Tumor spectrum in cancer family syndrome (hereditary nonpolyposis colorectal cancer). AB - The distribution of different malignant tumors was studied in 40 cancer family syndrome (CFS) families with 315 affected family members and a total of 472 separate tumors or malignant diseases. Only families with three or more first degree family members with colorectal carcinoma were included and other CFS characteristics were required in at least two cases. Colorectal (63%), endometrial (8%), gastric (6%), biliopancreatic (4%), and uroepithelial carcinomas (2%) were the most frequent, and represent the tumors typical of CFS. Families with endometrial cancer (23, 57%) and those without endometrial cancer (17, 43%) did not differ in frequencies of other extracolonic carcinomas. Families with endometrial cancer has more affected members and especially more affected female members than those without endometrial cancer (means, 9.7 and 4.9 versus 5.5 and 1.6 per family, respectively). The authors conclude, therefore, that the occurrence of one or more types of extracolonic tumors in members of CFS families does not provide a firm basis for subdividing the CFS (or hereditary nonpolyposis colorectal carcinoma syndrome. PMID- 1913483 TI - Cisplatin-based chemotherapy in a renal transplant recipient. AB - Cisplatin-based chemotherapy is the treatment of choice for metastatic testicular cancer; however, the safety of conventional regimens in renal transplant recipients has been questioned. The authors report the course of a renal transplant recipient successfully treated with a cisplatin-based chemotherapy regimen for testicular seminoma and review three additional cases that have been reported in the English language literature to date. Emphasis is placed on review of the safety, optimal administration, and appropriate monitoring of cisplatin and controversy regarding the need for continued administration of immunosuppressive therapy. PMID- 1913484 TI - Pain management in the opioid-addicted patient with cancer. AB - Two patients with an active or recent history of opioid abuse had painful complications of cancer that required narcotic analgesic therapy. Initial pain management was difficult due to issues of distinguishing tolerance from disease progression, concurrent methadone maintenance, and drug-seeking behavioral patterns. Pain control was achieved with psychological support, medication contracts, and attention to proper dosing of opioids. Suggested guidelines for management of these cases are offered. PMID- 1913485 TI - Hematopoietic and lymphoproliferative cancer among male veterans using the Veterans Administration Medical System. AB - Hematopoietic and lymphoproliferative cancer risk among the 3.7 million United States male veterans who use the Veterans Administration (VA) medical system annually was assessed using age-specific incidence curves and cumulative incidence rates. Relative risk comparing the VA with general population risk estimates from the Surveillance, Epidemiology, and End Results (SEER) data were increased significantly for all malignancies examined. The VA sample showed risk increases of 93% for Hodgkin's disease, 20% for non-Hodgkin's lymphomas, 51% for multiple myelomas, and 40% for all leukemias. Among the leukemia subtypes, the observed risk increases were 54%, 23%, 80%, and 46% for lymphocytic, granulocytic, monocytic, and other forms of leukemia, respectively. The large size of the sample and the consistency of risk estimates with two different methods confer validity and strength to these findings. The possible relevance of the high prevalence of tobacco and alcohol use in this population sample to the current findings is discussed and the need for further analytic investigations to explain the increases in risk is emphasized. PMID- 1913486 TI - Caregiver burden and unmet patient needs. AB - Four-hundred eighty-three patients with cancer and their informal caregivers were studied. Patients reported on met and unmet needs in personal care activities (bathing and dressing), instrumental activities (heavy and light housekeeping, cooking, shopping), transportation (medical and general), and home health care (health/treatment assistance). A minority (18.9%) experienced an unmet need. Hierarchical logistic regression was used to identify significant predictors of any unmet need. Patients were more likely to report any unmet needs when their illness/treatment resulted in restricted activity days, when their financial resources were reduced enough for them to apply for Medicaid or Public Assistance, or when their caregivers were not their spouses. Although in general, the likelihood of an unmet need decreased as the number of domains of assistance provided by the caregiver increased, if that care was associated with a high level of burden, the odds of a patient reporting an unmet need actually increased. PMID- 1913487 TI - Mathematical model for control of microscopic disease with radiation. PMID- 1913488 TI - Multiple cavitating pulmonary nodules in Hodgkin's disease. AB - Although pulmonary involvement in Hodgkin's disease is common, the presentation with multiple cavitating lung lesions is exceedingly rare, having been described in only five patients. The authors present a case report of a 27-year-old woman with nodular sclerosing Hodgkin's disease treated with conventional chemotherapy and autologous bone marrow transplantation. The patient relapsed with multiple cavitating lung lesions requiring open-lung biopsy for diagnosis. PMID- 1913489 TI - Alternating weekly doxorubicin and 5-fluorouracil/leucovorin followed by weekly doxorubicin and daily cyclophosphamide in stage IV breast cancer. A Southwest Oncology Group study. AB - Twenty-seven women with metastatic breast cancer were treated with doxorubicin (Adriamycin, Adria Laboratories, Columbus, OH) every other week, alternating with 5-fluorouracil (5FU) and high-dose calcium leucovorin, for a 12-week induction regimen, followed by weekly doxorubicin and oral daily cyclophosphamide. Twenty five women were eligible and evaluable. Of these, complete response occurred in two patients (8%) and partial response in six patients (24%), for a total response rate of 32%. Toxicity was similar to that seen in previous Southwest Oncology Group (SWOG) trials in this patient population. Response rates in this study were inferior, with comparable median survivals to those of previous SWOG studies that are reviewed. Additional, more dose-intensive approaches incorporating newer approaches to the administration of cancer chemotherapeutic agents are planned. PMID- 1913490 TI - The yield of routine chest radiography in children with cancer hospitalized for fever and neutropenia. AB - A routine admission chest radiograph (CXR) in pediatric patients with cancer who are admitted to the hospital for fever and neutropenia has been advised because the signs and symptoms of pneumonia may be absent. The authors studied 131 consecutive patient admissions for fever and neutropenia to evaluate the diagnostic yield of routine CXR. All patients had a complete history, physical examination, complete blood count, blood culture, urinalysis, urine culture, and CXR. Patients routinely started ceftazidime monotherapy. Results of the CXR were correlated with the presence or absence of signs and symptoms of respiratory disease. Of 128 CXR results, 26 (20%) were abnormal (13 with known malignant disease, 2 with atelectasis, 3 with peribronchial cuffing, and 8 with pneumonia [6%]). Three patients with pneumonia were asymptomatic. Therefore, only 3 of 128 patients (2.3%) had pneumonia on CXR not suspected by physical examination. None would have had initial therapy modified based on the CXR finding alone. The authors concluded that the incidence of pneumonia in a child with fever and neutropenia is low and that routine CXR at diagnostic evaluation is unnecessary in the asymptomatic ambulatory patient. PMID- 1913491 TI - Second and third responses to the same induction regimen in relapsing patients with multiple myeloma. AB - From September 1975 to December 1986, 115 consecutive previously untreated patients with multiple myeloma (MM) were treated with combination chemotherapy consisting of BCNU, cyclophosphamide, melphalan, vincristine, and prednisone (M 2). No patients were excluded or lost during follow-up. Forty-three percent of the patients were Stage I plus II, and 57% were Stage III. Thirty-eight patients (33%) had blood urea nitrogen greater than or equal to 40 mg/dl (substage B). Reaching an objective response treatment was stopped, generally after 1 year, and restarted at relapse. After induction therapy, 94 patients (82%) responded and had a median duration of response (MDR) of 22 months. After first relapse, 26 of 38 patients (69%) responded again to the same regimen and had an MDR of 11 months. This response rate and MDR are significantly lower than the ones achieved in induction chemotherapy. After second relapse, 7 of 16 patients (44%) again responded with an MDR of 3.5 months. The median survival time (MST) was 50.5 months for all patients. The most relevant side effect was leukopenia. No case of secondary leukemia was noticed. The authors conclude that patients with MM can be treated safely without maintenance therapy after reaching remission because a high response rate can be obtained in first and even second relapse. The planned treatment pause at remission does not adversely affect the survival time. Secondary leukemia is infrequent after this policy. Quality of life improves during the treatment pause. PMID- 1913492 TI - Reduced drug accumulation as the mechanism of extreme clinical resistance to methotrexate in the human T-cell leukemia xenograft, LALW-2. AB - The mechanisms were examined that underlie the extreme resistance to methotrexate (MTX) by near diploid leukemic T-cells (LALW-2) exposed to the drug only during the course of therapy administered to the patient of origin. Despite the LALW-2 cells being highly resistant to MTX (inhibitory dose for 50% of cells, more than 10(-3) mol/l), southern blot analysis did not show any amplification of the dihydrofolate reductase gene, nor was there any evidence, by comparison with drug sensitive CCRF-CEM cells, that the gene was overexpressed. Kinetic analysis of dihydrofolate reductase activity in the presence of MTX provided no basis for attributing resistance in LALW-2 cells to a change in enzyme structure. By contrast, studies of MTX accumulation revealed that the LALW-2 cells accumulated significantly less drug than either CCRF-CEM cells or a MTX-resistant CCRF-CEM subline with a characterized transport defect. These data suggest that extreme MTX resistance in LALW-2 cells is mediated by reduced drug accumulation in the absence of any effect on the target enzyme. PMID- 1913495 TI - American Cancer Society Workshop on Breast Reconstruction: prospects/ problems. Miami, Florida, October 26-28, 1990. PMID- 1913494 TI - Osteoblastoma response to chemotherapy. AB - An 8-year-old boy had an osteoblastoma of the body of C2. After attempted excision, the tumor recurred rapidly and massively. The tumor shrank progressively after treatment with high-dose methotrexate, doxorubicin, and cisplatin. The patient has stopped treatment and been stable for 33 months. Surgical excision remains the treatment of choice for osteoblastoma. Chemotherapy may be useful in selected patients with a recurrent, aggressive tumor or in patients with surgically inaccessible disease. PMID- 1913496 TI - The role of reconstruction in breast cancer. AB - Lumpectomy and irradiation is an increasingly popular treatment option for women with breast cancer. Currently, modified radical mastectomy is selected about as often. Most women choosing to have a mastectomy desire reconstruction to improve the cosmetic result; this procedure can be done immediately or at a later time. If immediate reconstruction using a plastic implant is selected, an expander can be used if the skin cover is inadequate. A myocutaneous flap can be used either immediately or later and whether sufficient skin is available. The trans rectus abdominal myocutaneous (TRAM) flap is increasingly popular because a large amount of tissue can be transferred and the cosmetic blemish from tissue transfer is preferable on the lower abdomen than elsewhere. Treatment costs are of some importance. The cheapest procedure is the modified radical mastectomy; lumpectomy with iridium implant is the most expensive, and the other treatments fall in between. PMID- 1913493 TI - Liver and tumor uptake and plasma pharmacokinetic of arterial cisplatin administered with and without starch microspheres in patients with liver metastases. AB - Arterial chemoembolization of liver tumors should improve regional treatment by reducing native blood flow of the whole organ and redistributing residual flow toward hypovascular masses. Plasma cisplatin pharmacokinetics and its tissue uptake and relative tumor and liver vascularity were studied during surgical placement of arterial catheters in four patients and in four patients with colorectal metastases given intraoperative arterial cisplatin (DDP, 25 mg/m2), with an without coadministration of 600 mg degradable starch microspheres (DSM). Mean (+/- standard deviation) filterable plasma platinum levels peaked later (2 minutes) and were significantly lower after DDP with DSM (1.23 +/- 0.69 micrograms/ml) than after DDP alone (2.13 +/- 0.43 micrograms/ml, P less than 0.05), with the area under the curve (AUC0-30 min) values of 15.8 +/- 5.5 and 25.1 +/- 3.8 micrograms x min/ml (P less than 0.05), respectively. No differences in urine excretion, total body clearance, or plasma protein binding of platinum were observed. Tissue biopsies were started 15 minutes after DDP administration and completed in all cases within 5 minutes. Tumor platinum concentrations were significantly higher after DDP with DSM (3.03 +/- 1.60 micrograms/g) than after DDP alone (0.67 +/- 0.49 micrograms/ml, P less than 0.05). Liver concentrations and tumor-liver ratios of platinum also were higher, although not significantly, after DDP with DSM. Preoperative vascularization, studied with arterial perfusion scan, influenced individual tissue drug uptake in cases given DDP alone, with the lowest tumor levels in cold masses. Very high and almost superimposable liver and tumor concentrations were measured in those receiving DDP and DSM. The latter phenomenon was irrespective of native vascularization, indicating that DSM administration induced both an increased whole-liver extraction of the drug and a redistribution of blood flow and flow-dependent tissue uptake of platinum. PMID- 1913497 TI - State-of-the-art breast reconstruction. AB - Many breast reconstruction procedures have been performed with success and satisfaction. These methods can be categorized as implant reconstruction, local tissue with implant, autologous tissue, and free flaps. Implant reconstruction, immediate or delayed, has been the easiest and most fulfilling experience for the surgeon and the patient. Local tissue with implant and autologous tissue are usually available to those patients with anterior chest tissue deficiency or those who prefer autologous tissue without the fear of implant material. Free flap reconstruction is often selected when no other procedures are appropriate for the patient. Individual procedures must be familiar to the patient and the surgeon. Other factors such as time involved, cost of hospital stay, recovery time, and associated complications are discussed in this article. Refinement and nipple areolar reconstruction are an intimate part of breast reconstruction, but these are usually the decisions made by the patient that must be respected. PMID- 1913498 TI - The effect of silicone-gel-filled implants on mammography. AB - Fifty-four women who had previously undergone breast augmentation underwent film screen mammography using both the standard implant compression technique and, when possible, the implant displacement technique. All had preaugmentation mammography available for evaluation. The area of mammographically visualized breast tissue before and after augmentation mammoplasty was measured using a transparent grid. Patients with subglandular implants had a mean 44% decrease of measurable tissue area with compression mammography and 36% decrease with displacement mammography. Patients with submuscular implants had a mean 25% decrease in measurable tissue area with compression mammography and 15% decrease with displacement mammography. Anterior breast tissue was seen better with displacement mammography, and posterior breast tissue was seen better with compression mammography. Most patients had some degree of parenchymal scarring and lower image quality after augmentation. State-of-the-art mammography was not possible in most patients whose breasts were augmented with silicone-gel-filled implants. PMID- 1913499 TI - Nonimaging aspects of follow-up in breast cancer reconstruction. AB - Follow-up of patients with breast cancer is directed to the early detection of recurrent or metastatic disease and the detection of new primary breast cancer. The survival benefit of early detection is limited to some patients with local failure or new primary tumors. That imaging is not used in follow-up of patients who have had breast cancer reconstruction is related to possible interference with this putative benefit by the reconstructive procedure. Such follow-up is accomplished by the patient's own surveillance, clinical examination, and laboratory testing supplemented by imaging studies. Clinical follow-up trials of women who have undergone breast reconstructive surgery show no evidence that locally recurrent breast carcinoma is masked when compared with follow-up of women who did not undergo reconstructive procedures. Reshaping of the contralateral breast to match the reconstructed breast introduces the possibility of interference with palpation as well as mammographic distortion in some women. This is an uncommon practical problem except when complicated by fat necrosis. PMID- 1913500 TI - Patient issues in breast reconstruction. AB - Breast reconstruction is not a new idea. Techniques have been developing since the late 1800s. The state of the art is such that the knowledge of its availability and success has significant effect on the willingness of women to seek earlier diagnosis and treatment. However, reconstruction is not for everyone. This paper examines the issues about knowledge, attitudes, and practices that either result in electing for or against reconstruction. Some issues involved are financial, others have to do with cosmetic appearance, and still others involve the medical and psychological affects. Identifying and understanding the issues from the point of view of the patient is important in providing support for the patient with breast cancer. PMID- 1913501 TI - Breast reconstruction. Update of psychosocial and pragmatic concerns. PMID- 1913502 TI - Psychosocial issues in breast reconstruction. PMID- 1913503 TI - Defining the role of reconstruction. PMID- 1913504 TI - Breast reconstruction. State-of-the-art for the 1990s. PMID- 1913505 TI - Implications for clinical management in patients with breast cancer. Long-term effects of reconstruction surgery. PMID- 1913506 TI - Patient/psychosocial issues. Patient and family education. PMID- 1913507 TI - Acromegaly and gastrointestinal cancer. AB - A cohort of 1041 men who were discharged from the hospital with a diagnosis of acromegaly were examined for subsequent cancer. With a mean follow-up time of 8.3 years, an increased rate of cancers of the digestive organs was observed (27 cases; standard incidence ratio [SIR], 2.0; 95% confidence interval [CI], 1.3 to 2.9). Rates were elevated for cancers of the esophagus (7 cases; SIR, 3.1), stomach (4 cases; SIR, 2.5), and colon (13 cases; SIR, 3.1). The increased risk of colon cancer in acromegaly is consistent with previous clinical reports and suggests opportunities for etiologic research and early cancer detection. It would seem prudent to also evaluate this risk in current research on the use of growth hormone in older individuals to increase muscle mass and reduce body fat. PMID- 1913508 TI - A prospective study on the treatment of retinoblastoma in 72 patients. AB - Seventy-two patients with retinoblastoma (RTB) (unilateral [47 patients] and bilateral [25 patients]) were studied for a period of 6 years. Treatment consisted of enucleation of those eyes that had severe involvement and was followed by radiation therapy and/or chemotherapy (systemic or intrathecal) according to clinical pathologic staging. All patients who underwent nonsurgical treatment received systemic chemotherapy. Intrathecal chemotherapy was administered when there was involvement of the central nervous system. Nonsurgical treatment consisted of radiation therapy and/or light coagulation, followed by enucleation if there was no response. The overall survival rates were 79% for unilateral disease (median follow-up time, 63 months) and 72% for bilateral disease (median follow-up time, 81 months). Vision was regained in 14 of 21 conserved eyes. PMID- 1913509 TI - The use of prophylactic eye drops during high-dose cytosine arabinoside therapy. AB - An ocular toxic reaction presenting as conjunctivitis or keratitis develops in a significant number of patients who are treated with high-dose cytosine arabinoside (ara-C). Although eye drops containing glucocorticoid reportedly decrease the incidence, they do not totally eliminate this side effect. In comparing this technique with artificial tears, both were found to be equally effective. The primary mechanism by which eye drops decrease ocular toxic reactions associated with high-dose ara-C is presumably due to dilution of intraocular concentrations of ara-C. PMID- 1913510 TI - A Southwest Oncology Group phase II Trial of recombinant tumor necrosis factor in metastatic breast cancer. AB - New approaches are needed in the treatment of advanced breast cancer. In vitro studies have shown that recombinant tumor necrosis factor (TNF) is a growth inhibitor for the MCF-7, ZR-75-1, and BT-20 human breast cancer cell lines. Based on these considerations, the Southwest Oncology Group performed a Phase II trial of recombinant TNF (Genentech) (150 micrograms/m2) given by 30-minute intravenous infusion on days 1 to 5 of every other week for 8 weeks. Patients with metastatic breast cancer who had received one prior chemotherapy regimen for advanced disease were eligible. Of the 22 patients who were entered, 3 were ineligible. Nineteen patients who had a performance status of 2 or less could be examined (median age, 53 years). One possible fatal toxic reaction has been seen in a patient who had intracranial bleeding caused by a previously undiagnosed brain metastasis; no other treatment-related deaths have occurred. Toxicity has included nausea, vomiting, fever, chills, myalgia, and fatigue. No Grade 4 toxicity has been observed. Grade 3 toxic reactions have included hypotension (two patients), diarrhea (one patient), transient leukopenia (two patients), and reversible elevations of liver function test values (two patients). No objective responses have been observed. Twelve of 19 patients have died (median survival time, 8.5 months). Recombinant TNF is inactive as a single agent in patients with previously treated metastatic breast cancer. PMID- 1913511 TI - Cytosine arabinoside and cisplatin for advanced breast cancer. A phase II study of the Cancer and Leukemia Group B. AB - Forty-four women with advanced breast cancer participated in a prospective clinical trial to evaluate the efficacy and toxicity of a regimen consisting of cytosine arabinoside and cisplatin. All patients had previously received chemotherapy. Three patients (7%) responded to therapy with response durations of 153, 160, and 441 days. The median time to disease progression and median survival time in all 44 patients were 2.3 and 5 months, respectively. This regimen had significant toxicity, with most patients experiencing severe or life threatening hematologic, renal, or infectious complications. This regimen cannot be recommended for previously treated patients with advanced breast cancer. PMID- 1913512 TI - A phase I study of an outpatient regimen of recombinant human interleukin-2 and alpha-2a-interferon in patients with solid tumors. AB - This study was undertaken to define the maximum tolerated dose (MTD) of recombinant interleukin-2 (IL-2) that could be combined with a fixed dose of alpha-2a-interferon (alpha-IFN) in an outpatient setting. The schedule called for IL-2 to be given by a 2-hour intravenous infusion 5 days a week for 4 weeks. The alpha-IFN was given at a dose of 6 x 10(6) U/m2/d intramuscularly 3 days per week (Monday, Wednesday, and Friday). The IL-2 dose was escalated in four dose levels from 1 to 4 x 10(6) U/m2/d. The MTD in this study of 17 patients was at the fourth dose level of IL-2 (4 x 10(6) U/m2/d). In addition to the usual IL-2 toxicities, debilitating fatigue limited outpatient administration of this dose. Although the response rate was low, with partial responses seen in only 1 of 15 patients, 2 of 5 patients with melanoma treated at the higher dose levels had objective tumor shrinkage with one partial and one minor response. Thus, an IL-2 dose of 3 x 10(6) U/m2/d combined with a recombinant alpha-2a-IFN dose of 6 x 10(6) U/m2/d is recommended for Phase II studies. PMID- 1913513 TI - Sufficient levels of quinine in the serum circumvent the multidrug resistance of the human leukemic cell line K562/ADM. AB - Reversal of multidrug drug resistance (MDR) has been achieved in vitro by a variety of agents including verapamil, quinidine, cyclosporine A, and amiodarone. The toxicity of these agents precludes the achievement of sufficient levels in the serum to circumvent efficiently the MDR in vivo. The authors previously demonstrated that quinine, the widely used antimalarial agent, is able to reverse primary resistance of rat colon cancer cells to anthracyclines. In this report, the efficiency of quinine formiate in reversing the doxorubicin (ADM) (Adriamycin, Adria Laboratories, Columbus, OH) resistance of the well-defined MDR human leukemic cell line K562/ADM was demonstrated. In culture medium, quinine is slightly less effective than verapamil in increasing the cytotoxicity and uptake of ADM when both drugs are used at the same concentration. A nontoxic dose of 5 micrograms/ml is necessary to reverse the MDR in K562/ADM cells. In patients receiving quinine formiate in a continuous intravenous infusion, a significant correlation (r = 0.84) was found between the serum levels of quinine and the ability of sera to increase ADM uptake in K562/ADM cells. When quinine is administered at a conventional dose (25 to 30 mg/kg/d), serum levels consistently reach more than 8 micrograms/ml without severe side effects; ear noises and vertigo are the dose-limiting side effects. At these concentrations, quinine induces a more than double increase in ADM uptake in K562/ADM cells. Pharmacokinetic data indicate that quinine should be administered 24 to 36 hours before anti-cancer drugs in clinical trials that test its efficiency as a modifier of MDR in human hematologic malignant neoplasms. PMID- 1913514 TI - Successful use of cisplatin to treat metastatic seminoma during cisplatin-induced acute renal failure. AB - A chemotherapeutic regimen including cisplatin was administered to a man with extragonadal seminoma and cisplatin-induced acute renal failure. Three doses of cisplatin (30, 50, and 100 mg/m2) were given in conjunction with hemodialysis. Pharmacokinetic data for free and total plasma platinum were obtained. The patient also received one dose of carboplatin and a course of radiation therapy. Complete remission was achieved, and useful renal function returned. Cisplatin can be used successfully during acute renal failure. PMID- 1913515 TI - Inhibition of tumor implantation at sites of trauma by plasminogen activators. AB - The authors report on the influence of plasminogen activators (PA) on implantation of TA3Ha mammary tumor cells in the healing hepatic wounds of syngeneic strain A mice. Intravenously injected TA3Ha cells, although they rarely metastasize to the liver, formed tumors in the hepatic wounds of a significant percent (42%, P less than 0.0001) of mice. The frequency of tumor formation declined as the interval between surgery and tumor cell inoculation was increased. Furthermore, preexposure of cells to fibrinogen, fibronectin, laminin, or peptides containing the arginine-glycine-aspartic acid-serine residues dramatically reduced the frequency of tumor formation in the hepatic wounds. These results indicate that TA3Ha cells interact with fibrinogen-related proteins in the wound to aid their attachment and growth. Because these proteins are susceptible to digestion by plasmin, PA were used in this study to examine whether administration of these drugs to the mice would modulate tumor formation in the liver wounds. Among the PA tested, human plasmin B-chain-streptokinase complex (B-SK) and recombinant tissue plasminogen activator (t-PA) inhibited tumor implantation in a dose-related manner. Administration of 900 units (U) of B SK or 3300 U of t-PA per mouse reduced the frequency of tumor formation from 42% to 0% (P = 0.02) and 11% (P = 0.02), respectively. The B-SK was complexed with p nitrophenyl-p-guanidinobenzoate; it did not activate the plasminogen or inhibit tumor formation in the hepatic wounds. Although urokinase activated the plasminogen, it did not inhibit tumor implantation in the hepatic wound. Heparin, an anticoagulant that prevents conversion of fibrinogen to fibrin without being fibrinolytic, had no influence on tumor formation in the hepatic wounds. The PA can generate plasmin that digests the cell attachment proteins in wounds and consequently inhibits tumor cell attachment. PMID- 1913516 TI - Histopathologic characteristics of early adenocarcinoma in Barrett's esophagus. AB - To elucidate the early events of cancer development in the columnar cell-lined lower esophagus, 13 esophagectomy specimens with early adenocarcinoma (T1) were histopathologically studied and the morphometry of the lesion was performed on a histologic map. Eleven (84.6%) of the 13 early Barrett's carcinomas were contiguous to both the distinctive specialized-type Barrett's mucosa and squamous epithelium. Furthermore, ten (76.9%) of the 13 tumors had residual squamous islands on the surface. These data suggest that carcinomas in Barrett's esophagus mostly develop at a place very close to the squamocolumnar epithelial border. The distance from the tumor center to the nearest squamous epithelium, including squamous islands, was 2 cm or less in all cases but one. Therefore, the authors conclude that the primary site of cancer development in Barrett's esophagus is the metaplastic columnar-lined area, particularly of specialized type, within 2 cm from the squamocolumnar epithelial border. PMID- 1913517 TI - Downregulation of specific protein carboxylmethyltransferase immunoreactivity in human endometrial carcinoma. AB - Protein carboxylmethyltransferases (PCMT), enzymes that methylate free carboxyl groups of proteins, are involved in functional modification of various proteins including those of age-damaged proteins and the oncogenic ras proteins. Several species of PCMT are associated with these modifications. By using western blot analysis and specific antibodies raised against one type of PCMT, a 30-kilodalton (KD) cytosolic enzyme from Torpedo electric organ was identified in human erythrocytes and endometrium. The high specificity of the antibodies made it possible to compare levels of immunoreactive 30-KD PCMT protein in normal human endometria and endometrial carcinomas. Assays done on samples from 23 patients indicated the average levels of immunoreactive 30-KD PCMT in endometrial carcinomas was one fifth that of normal endometrium. The sensitivity of the assay was 83%, and its specificity was 90%. These results suggest that levels and activity of the 30-KD PCMT may be downregulated to maintain the phenotypic expression of the endometrial carcinoma. These assays may be used to assist in the detection of endometrial carcinomas. PMID- 1913518 TI - Pseudomesotheliomatous carcinoma of the lung. An immunohistochemical and ultrastructural study of three cases. AB - The authors report immunohistochemical and electron microscopic studies on three new cases of pseudomesotheliomatous carcinoma of the lung. Although the distinct clinical and histopathologic features of this peripheral lung cancer were described many years ago, its recognition as a distinct variety of lung carcinoma has not gained wide acceptance. Little is known of its incidence and only few cases have been reported until now. In the current study the authors demonstrate the epithelial nature of this tumor by its positive immunohistochemical reactions for epithelial membrane antigen (EMA), carcinoembryonic antigen (CEA), Leu-M1, B 72.3, and surfactant apoprotein. The ultrastructural features and staining of nuclear inclusions with surfactant apoprotein indicate differentiation into type II cells as found in other forms of peripheral lung adenocarcinoma. Despite these morphologic similarities, pseudomesotheliomatous carcinoma is characterized by extensive invasion of the pleura and rapidly fatal course. Because of this biologic behavior it deserves recognition as a distinct variant of peripheral lung carcinoma. PMID- 1913519 TI - Primary pulmonary adenocarcinoma with enteric differentiation. AB - A pulmonary neoplasm with cytologic characteristics typical of differentiated small intestinal epithelium is reported. Individual cells showed features suggesting columnar absorptive, goblet, Paneth, and neuroendocrine cell differentiation. Thorough investigation and follow-up for 4 years did not identify a primary tumor other than in the lung. The occurrence of such a neoplasm at this site is evidence for the existence of a common stem cell in the lower respiratory and gastrointestinal tract mucosa. PMID- 1913520 TI - Coordinate elevation of serum markers in ovarian cancer but not in benign disease. AB - Effective screening for occult ovarian cancer will require a strategy that is both sensitive and specific. Preliminary data suggest that CA 125 is elevated at diagnosis in a majority of patients with ovarian cancer. Although CA 125 is sufficiently specific to prompt its evaluation as one component of a strategy to detect ovarian cancer in postmenopausal women, a further improvement in specificity would facilitate cost-effective screening. In an attempt to develop a more specific screening strategy, multiple markers were assayed in a panel of sera from 47 patients with ovarian cancer and in a separate panel of sera from 50 individuals with benign disease whose serum CA 125 levels exceeded 35 U/ml. Among the patients with ovarian cancer, elevations of CA 125 (greater than 35 U/ml) were observed in 91%, CA 15-3 (greater than 30 U/ml) in 57%, TAG 72 (greater than 10 U/ml) in 49%, placental alkaline phosphatase (PLAP) in 25%, human milk fat globule protein (HMFG) 1 in 77%, HMFG2 in 62%, and NB/70K in 57%. Among the 50 sera selected from patients with benign disease, CA 125 was more than 35 U/ml in 100% and more than 65 U/ml in 42%. Among those patients with benign disease and elevated CA 125, NB/70K was elevated in 62%, HMFG1 in 26%, and HMFG2 in 12%, whereas TAG 72 and CA 15-3 were elevated in only 6% and 2%, respectively. In addition PLAP appeared promising; elevated enzyme levels were not found in the benign disease group. Among patients with ovarian cancer with CA 125 levels more than 35 U/ml, either TAG 72 or CA 15-3 was elevated in 77%. In the false-positive group, only 6% had elevations of one or the other marker. The CA 125 levels in cancer patients were, however, substantially greater than in patients with benign disease. If sera from patients with ovarian cancer were diluted to a range comparable to that found in benign disease, at least one of the two confirmatory tests was elevated in 63% of the samples from the malignant cases. Consequently, use of CA 15-3 and TAG 72 in combination with CA 125 can increase the apparent specificity of the CA 125 assay for distinguishing malignant from benign disease. Prospective studies will be required to test critically whether the use of additional serum markers in combination with the CA 125 assay would contribute to the specificity of a cost-effective screening strategy for ovarian cancer. PMID- 1913521 TI - Granular cell tumor of a digital nerve. AB - Granular cell tumor is an infrequently encountered albeit not rare neoplasm considered to be of neuroectodermal origin. An example of a benign granular cell tumor originating within a digital nerve is presented. The authors employed routine light microscopic techniques and immunostaining which demonstrate features of the granular cells reflecting structural and functional characteristics of Schwann's cells and support neuroectodermal derivation. Granular cell tumor is ubiquitous in location but occurs more frequently in tongue, skin and subcutaneous tissue. Clinical features are not specific, and a histologic evaluation is required for diagnosis. Circumscription and lack of cellular pleomorphism define a benign process. However, irrespective of its histologic appearance, the biologic potential is uncertain. Complete excision suffices as treatment for benign tumors. PMID- 1913522 TI - Malignant transformation of aneurysmal bone cyst, with an analysis of the literature. AB - An 11-year-old girl had a lytic, benign-appearing, expansive lesion of the distal tibia radiologically interpreted as an aneurysmal bone cyst (ABC). Tissue from two extensive curettage procedures was also histologically diagnosed as ABC. Approximately 50 months after the onset of symptoms, and 28 months after her last curettage, a highly pleomorphic osteosarcoma developed. The patient had not received prior radiation therapy. The cases in the literature of possible malignant transformation of ABC are reviewed. The authors separate their case from telangiectatic osteosarcoma, and from "aneurysmal bone cyst-like osteosarcoma." PMID- 1913523 TI - DNA content flow cytometry as a prognostic factor for node-positive breast cancer. The role of multiparameter ploidy analysis and specimen sonication. AB - The DNA content was analyzed in paraffin-embedded material from 167 patients with node-positive breast cancer to learn whether specimen sonication and multiparameter ploidy analysis (MPPA) (using DNA content and light scatter) could improve the strength of ploidy as a prognostic variable. Sonicated specimens were found to have fewer aggregates, a lower percentage of cells in S-phase (%S) and G2M phase than the corresponding nonsonicated specimens. The results using MPPA predicted the prognosis better because they allowed detection of small aneuploid peaks in histograms classified as diploid or tetraploid using DNA content alone. Ploidy was a significant univariate factor, and patients with tetraploid tumors had the best survival. In the multivariate analysis, if other routine factors were examined preferentially, ploidy and %S did not provide additional prognostic information for survival. This study of paraffin-embedded breast cancers suggested that sonication and MPPA may improve the ploidy analysis in certain cases and that tetraploidy may be a favorable ploidy pattern in this group. PMID- 1913524 TI - Ascitic fluid analysis for the differentiation of malignancy-related and nonmalignant ascites. Proposal of a diagnostic sequence. AB - The authors tried to differentiate malignancy-related from nonmalignant ascites with a sequence of sensitive followed by specific ascitic-fluid parameters. There were four results of this study. First, of nine parameters investigated in a first series of 48 patients, 28 with nonmalignant and 20 with malignancy-related ascites, ascitic-fluid cholesterol and fibronectin yielded the best negative predictive value of 92% each. Carcinoembryonic antigen (CEA) and cytologic examination both showed a positive predictive value of 100%. Second, combining cytologic examination (sensitivity, 70%) and CEA determination (sensitivity, 45%) increased the sensitivity to 80%. Third, cytologic findings were negative in all ascitic-fluid samples with a cholesterol concentration below the cutoff value of 45 mg/100 ml. Fourth, based on the results of the first series of 48 patients, the diagnostic sequence with cholesterol as a sensitive parameter, followed by the combination of cytologic examination and CEA determination as specific parameters, was tested in a second series of 71 patients, 37 with nonmalignant and 34 with malignancy-related ascites. Again cytologic examination was negative in all samples with cholesterol levels below 45 mg/100 ml. In the total of 119 patients, this diagnostic sequence did not identify 9% of patients with malignancy-related ascites, and 82% of samples classified as malignancy related by cholesterol levels above 45 mg/100 ml were confirmed by positive cytologic examination and/or CEA level above 2.5 ng/ml. Thus, a diagnostic sequence with ascitic-fluid cholesterol determination, followed by cytologic examination and CEA determination, in samples with cholesterol levels above 45 mg/100 ml should permit a cost-efficient routine differentiation of malignancy-related from nonmalignant ascites. PMID- 1913525 TI - Localization of endocrine tumors of the pancreas with endoscopic ultrasonography. AB - High-frequency endoscopic ultrasonography (EUS) was used to image the pancreas through the wall of the stomach and duodenum in 12 patients with clinically suspected pancreatic endocrine tumors. In another patient, endocrine tumors in the wall of the duodenum were imaged by EUS. The findings were compared with those obtained by dynamic computed tomography (all patients) and selective angiography (eight patients). Laparotomy was done in eight patients. In our 13 patients, EUS detected endocrine tumors of the pancreas and duodenum in ten patients. More than one tumor was evident in five patients, including one of two patients with multiple endocrine neoplasia syndrome type I. In the eight patients treated surgically, there was one false-positive finding as a result of hypertrophic peripancreatic lymph nodes and one false-negative finding, in retrospect obviously imaged but incorrectly interpreted. The technique of EUS imaged small tumors in the pancreas (0.5 to 2.0 cm in diameter) in five patients where dynamic computed tomography and selective angiography were negative, but surgery and pathologic examination confirmed the EUS findings. This technique appears to be an important new addition to the battery of tests used for preoperative localization of endocrine tumors of the pancreas. PMID- 1913526 TI - Strongyloides hyperinfection in two patients with lymphoma, purulent meningitis, and sepsis. AB - Strongyloides stercoralis hyperinfection syndrome is a rare complication of strongyloidiasis that occurs in immunosuppressed patients. It is caused by increasing autoinfection of the host by the nematode, leading to serious superimposed enterobacterial sepsis. Once established, it has a high fatality rate. Two cases are reported of Strongyloides hyperinfection in patients with lymphoma who presented with purulent meningitis. Both were receiving combination chemotherapy that included high-dose corticosteroids, and neither was granulocytopenic at infectious onset. The patients had respiratory insufficiency that required mechanical ventilation and serious septic episodes. Both were treated with thiabendazole, and one survived with clearance of the larvae. These cases illustrate the possibility of strongyloidiasis hyperinfection as an underlying diagnosis of purulent meningitis and serious septic episodes in lymphomatous patients. It may occur even without granulocytopenia. PMID- 1913527 TI - An eosinophilic fibrohistiocytic lesion of bone marrow in a patient with Hodgkin's disease. A potential for morphologic confusion. AB - The eosinophilic fibrohistiocytic lesion of bone marrow (EFLBM) is characterized by collections of elongated "fibrohistiocytic" cells in association with lymphocytes, eosinophils, and plasma cells. The fibrohistiocytic cells are mast cells, and many investigators include this lesion (EFLBM) as a localized form of mastocytosis. The etiology and clinical significance of these lesions remains unclear. The morphologic features of these lesions point to a wide differential diagnosis that includes Hodgkin's disease. Currently, however, there are no recorded cases of well-defined Hodgkin's disease with these lesions. A case of Hodgkin's disease in which such lesions complicated the interpretation of serial bone marrows is reported. This case illustrates how the presence of these lesions could potentially influence therapeutic intervention. PMID- 1913528 TI - Chondrosarcoma of the larynx after radiation treatment for vocal cord cancer. AB - The case of a 57-year-old man with chondrosarcoma of the laryngeal cartilage is presented, occurring 16 years after radiation treatment for squamous cell carcinoma of the right true vocal cord. Chondrosarcoma of the larynx is an uncommon tumor. The location, grade, and time elapsed from initial treatment make it probably that this patient's chondrosarcoma is associated with his prior radiation treatment. However, it is a rare occurrence, this being the second case reported in the literature. PMID- 1913529 TI - Multiple endocrine syndrome type IIb in early childhood. AB - A 3-week-old girl who was born with club feet had signs of failure to thrive. On physical examination the child appeared normal; she had no abnormalities in the mucous membranes of the mouth, the eyelids, or in the neck, and her other systems, including heart, chest, abdomen, and neurologic systems, were clinically normal. Radiologically, the gastrointestinal tract was normal, but rectal biopsy showed neuromas. Her serum calcitonin level was measured both at basal and after pentagastrin stimulation at 5 weeks of age and found to be high, but whether it was consistent with the normal level at this early age or was caused by medullary thyroid carcinoma was not clear. At 3 months, the corneal nerves of both eyes were examined and showed considerable thickening, and multiple endocrine syndrome type IIb was suspected. The serum calcitonin level at 8 and 14 months was increased. A total thyroidectomy was done, and C-cell nodular hyperplasia and adenomatosis was found in the isthmus. The postoperative serum calcitonin level decreased to low normal and did not increase after pentagastrin stimulation. To the authors' knowledge, this case represents the youngest patient diagnosed with multiple endocrine syndrome type IIb in the absence of family history of the disease. PMID- 1913530 TI - Breast cancer and paraneoplastic cerebellar degeneration. AB - Of the remote effects of cancer on the neurologic system, paraneoplastic cerebellar degeneration (PCD), characterized by global cerebellar dysfunction, is second only to paraneoplastic neuropathies in frequency. Recent evidence, including the finding of anti-Purkinje cell (now termed anti-Yo) antibodies directed against specific protein antigens shared by Purkinje's and tumor cells, supports an autoimmune etiology for this disorder. Increasingly, a link between breast cancer and PCD is being recognized. The authors report a case, as well as a comprehensive overview, of 62 women with breast cancer and PCD, identified through a Medline (National Library of Medicine, Washington, DC) computer search (1966 to 1991) and comprehensive reference follow-up of the medical literature. The current understanding of the pathophysiology of PCD, with particular emphasis upon those features both salient and unique to breast cancer, is discussed. Whereas PCD will affect only a small number of patients with breast cancer, recognition of this syndrome is important. Anti-Purkinje cell (anti-Yo) antibody titers are now commercially available through several reference laboratories, and a serum anti-Purkinje cell antibody titer will assist in establishing the diagnosis. Presence of consistent symptoms and elevated titers of anti-Yo antibodies should prompt a search for an otherwise occult, and potentially treatable, malignancy. Only therapy initiated early in the patient's course appears to be of benefit. Finally, investigations into the pathogenesis of this syndrome may shed further light upon other diseases presumed secondary to autoimmune dysfunction. PMID- 1913531 TI - Sarcoid-like lymphadenopathy mimicking metastatic testicular cancer. AB - A case of nonseminomatous testicular cancer and enlarged mediastinal lymph nodes, which were interpreted as metastases, is reported. When there was no change after two courses of chemotherapy, a mediastinoscopy was performed and the results showed sarcoidosis. PMID- 1913532 TI - Cancer and other causes of childhood mortality in Bombay, India. AB - Mortality from cancer and other diseases from 1964 to 1984 and their contributions in 1984 to premature mortality in Bombay, India, were studied. Cancer was the ninth and tenth cause of death in boys and girls younger than 15 years of age, respectively, in 1984. Prematurity and infectious diseases contributed most to years of potential life lost by children younger than 5 years of age in 1984; cancer, heart disease, and accidents-injury became important in children older than 5 years. When currently high mortality rates in infants and children younger than 5 years of age are reduced, cancer may become a greater childhood health problem. Approximately 5% of male and 3% of female patients with cancer in six hospital and three population-based cancer registries in India were children younger than 15 years of age. Cancer mortality declined from the rate during 1964 to 1972 to the rate during 1973 to 1984 by about 40% in children younger than 5 years old and in girls of 10 to 14 years of age and by 7.5% and 14% in the 5 to 9-year-old boys and girls, respectively. It increased by 12% in the 10 to 14-year-old boys. Early diagnosis and treatment of cancer in children older than 5 years of age may yield increased productive person-years of life. PMID- 1913533 TI - Time trends in malignant melanoma of the upper limb in Connecticut. AB - Time trends in the incidence of malignant melanoma of the anatomic subsites of the upper limb in Connecticut from 1935 to 1984 were examined. Among males, the incidence of melanoma of the hand was stable, in sharp contrast to the 15-fold to 16-fold increase in the upper arm and forearm. Among females, the 3-fold increase in melanoma of the hand was substantially less than the 12-fold to 14-fold increase in the upper arm and forearm. However, melanoma of the dorsal surface of the hand in females increased sevenfold. These results are in partial agreement with the hypothesis that the hand would be relatively resistant to increased melanoma incidence because it has continually been a sun-exposed site over the decades. The results contradict the hypothesis that the rise in incidence would be greater in the upper arm (a usually unexposed site that has received increasing exposure due to changes in recreation and dress habits) than in the forearm (a site of intermediate exposure). PMID- 1913534 TI - Effect of lymph node irradiation in operable breast cancer. PMID- 1913535 TI - Age as a prognostic factor in multiple myeloma. PMID- 1913536 TI - 4F2 expression by non-Hodgkin's lymphoma. PMID- 1913537 TI - Multiple myeloma in the geriatric patient: reply to Pascali and Pezzoli. PMID- 1913538 TI - Radiation therapy in the management of early stage Hodgkin's disease presenting in later life. AB - This study examined the contention that although elderly patients with Hodgkin's disease have a worse prognosis overall than younger patients, a subgroup of older patients fit enough to be managed like younger patients can fare just as well. A retrospective analysis was made on 29 patients older than 60 years of age with Stage I and II Hodgkin's disease treated by radiation therapy alone. Fourteen of these patients were managed optimally, i.e., were adequately staged (defined by one or more of the following: laparotomy, computed tomography [CT] scan, and/or lymphangiogram), followed by radical radiation therapy (mantle or inverted-Y). The remaining 15 patients, because of their general medical condition, were managed suboptimally with limited staging and/or involved-field irradiation. None of the 14 patients managed optimally relapsed over a median of 4.75 years of follow-up compared with 10 of 15 patients in the suboptimal group. For the optimally managed versus suboptimally managed groups, the actuarial 5-year disease-free survival rates were 61% and 6%, respectively; the actuarial overall survival rates (death from all causes) were 61% and 19%, respectively; and the disease-specific survival rates were 100% and 39%, respectively. Only three of the patients irradiated radically had acute complications severe enough to warrant a break in treatment. In the opinion of the authors, those elderly patients able to tolerate adequate staging and radical radiation therapy can anticipate a high likelihood of cure. PMID- 1913539 TI - Cisplatin in advanced salivary gland carcinoma. A phase II study of 25 patients. AB - A prospective Phase II study was carried out to test cisplatin (CDDP) as a single agent in salivary gland carcinomas. CDDP was administered (100 mg/m2) every 3 weeks to 25 consecutive patients with either recurrent or locally advanced salivary gland carcinoma. Six patients had received prior chemotherapy, and the other patients had had only surgery or radiation therapy or no treatment at all. The response rate was 18% (95% confidence interval [CI], 6% to 41%). Response duration was between 5 and 9 months. Median overall survival time was 14 months. CDDP is a moderately active drug in salivary gland carcinomas. It should be included in multidrug regimens to be tested in prospective studies, which are difficult to carry out due to the rarity of these tumors. PMID- 1913540 TI - Transurethral resection of the prostate and metastatic prostate cancer. AB - Demonstration of malignant cells in blood specimens collected during transurethral resection of the prostate (TURP) has implicated TURP in the dissemination of prostatic cancer. Of 153 patients who underwent radiation therapy for prostate cancer between January 1977 and June 1990 and were retrospectively analyzed, 93 were evaluable. Fifty-nine patients required TURP before radiation therapy for prostatic obstruction (BPH and/or cancer); the remaining 34 patients underwent radiation therapy after fine-needle aspiration biopsy. No statistically significant difference in failure rate could be detected between these groups, with a failure rate of 47% (28 of 59 patients) at a median follow-up time of 49 months (range, 8 to 146 months) in the TURP group versus a failure rate of 47% (16 of 34 patients) at a median follow-up time of 50 months (range, 3 to 122 months) in the group who underwent biopsy only (Fisher's exact test, P = 0.23). Within the confines of this retrospective study, it appeared that TURP did not enhance the development of metastatic disease. PMID- 1913541 TI - Etoposide, cyclophosphamide, cisplatin, and doxorubicin as neoadjuvant chemotherapy for osteosarcoma. AB - The authors evaluated the combination of etoposide/cyclophosphamide (VP/CY) as initial, presurgical therapy for patients with osteosarcoma and found an 88% response rate for the primary tumor and any metastases. After definitive, limb salvage surgery and adjuvant chemotherapy with etoposide, cyclophosphamide, cisplatin, and doxorubicin, patients without metastases at diagnosis whose cases were followed for a median of 2 years from diagnosis achieved a relapse-free survival (RFS) probability of 78% +/- 9%. This result is equivalent to the best adjuvant chemotherapy results reported to date. Patients without metastases at diagnosis had significantly better RFS probability (78% +/- 9%) than those with metastases at diagnosis (0%). Transient, severe myelosuppression has been the only major toxicity of the VP/CY courses. No irreversible organ damage or toxic deaths have been seen in patients enrolled in this study. The authors conclude that the combination of VP/CY is effective treatment for osteosarcoma, and when combined with cisplatin/doxorubicin (CIS/DOX), is as effective as any previously reported chemotherapy for osteosarcoma. PMID- 1913543 TI - Endocervical gland involvement by cervical intraepithelial neoplasia grade III. Predictive value for residual and/or recurrent disease. AB - The prognostic significance for residual or recurrent disease of cervical intraepithelial neoplasia Grade III in endocervical glands by cone biopsy was examined in 341 consecutive patients diagnosed from 1979 through 1983 and followed through 1988. Treatment by hysterectomy, within 8 weeks of cone biopsy, was done in 96 patients. The only variable that could predict residual disease at hysterectomy was positive margins (P = 0.059). However, both positive margins and positive glands were (independently of one another and after the effects of length of follow-up, hospital of admission, and age at time of first diagnosis were held constant) highly significant predictors of residual or recurrent disease in the 245 women who did not undergo a hysterectomy (P = 0.000 for each). The authors therefore conclude that information concerning gland involvement on cone biopsy specimens should influence patient management. PMID- 1913542 TI - Cognitive function in children with leukemia. Effect of radiation dose and time since irradiation. AB - The effect of two cranial radiation (CRTX) doses and the time since radiation therapy on cognitive functioning were studied in 35 children who completed therapy for acute lymphoblastic leukemia (ALL). The patients were grouped according to CRTX dose (2400 or 1800 cGy) and evaluated for general intelligence, academic achievement, and visual motor integration. Those who received 2400 cGy (n = 20) scored ten points below those treated with 1800 cGy (n = 15) on verbal intelligence quotient and achievement tests of reading, spelling, and arithmetic. The effect of time since radiation therapy on these measures of cognitive function was significant (P = 0.001 to 0.03); the effect of CRTX dose was not. Visual motor integration scores in both groups fell below the 33rd percentile. The effect of CRTX dose and time since radiation therapy on visual motor integration and performance intelligence quotient were not significant. Thus, the interval between treatment and the emergence of cognitive impairments may be longer after lower CRTX doses, and deficits in nonverbal areas such as visual motor integration may appear first. A larger study is needed to confirm these findings from a limited sample of long-term survivors of ALL. PMID- 1913544 TI - Follicular Hurthle cell tumors of the thyroid gland. AB - A clinicopathologic study of 153 cases of thyroid follicular Hurthle cell tumor (HCT) is presented. Follow-up, available in all cases, ranged from 5 to 26 years (median, 9 years). These neoplasms were divided into three categories on the basis of presence and degree of capsular and vascular invasion, pattern of growth (follicular, trabecular, or solid), nuclear atypia, and necrosis. The categories were benign (90 cases), indeterminate (35 cases), and malignant (28 cases). All the tumors classified histologically as benign or indeterminate behaved in a clinically benign fashion. Of the 28 tumors classified histologically as malignant, 20 had a clinically malignant behavior. At survival analysis, no clinical or pathologic feature among the carcinomas was found to correlate with a fatal outcome. It is concluded that histologic criteria alone can distinguish benign from malignant HCT and that clinical or pathologic feature cannot predict behavior among the malignant tumors. PMID- 1913545 TI - Desmoplastic fibroma of bone. AB - Desmoplastic fibroma is a rare primary tumor of bone that histologically and biologically mimics the extra-abdominal desmoid tumor of soft tissue. This study reviews 27 cases of desmoplastic fibroma, consisting of 9 from the Mayo Clinic files and 18 from our consultation files. There was a male predominance, and 74% of the patients were in the first 3 decades of life. The most frequent sites of involvement were the metaphysis of long bones and the mandible. Radiographically, the tumors were lucent, expansile lesions with well-defined margins. Histologically, they contained slender spindle cells and various amounts of collagen fibers. En bloc resection is the treatment of choice because a high incidence of recurrence was noticed after lesional curettage. PMID- 1913546 TI - A tentative tumor-node-metastasis classification of thymoma. AB - To establish a tumor-node-metastasis (TNM) classification of thymoma, 207 thymoma patients seen at the First Department of Surgery, Osaka University, and the Second Department of Surgery, Nagoya City University, were evaluated. Lymphogenous and hematogenous metastases of thymoma were infrequent, but their frequency increased with the duration of the course. Lymphogenous metastasis was observed in few cases, but it was considered to progress from anterior mediastinal lymph nodes to intrathoracic and then to extrathoracic lymph nodes. No particular characteristics were observed in hematogenous metastasis. On the basis of these observations, a TNM classification of thymoma was established and applied it to 207 thymoma cases, but it had little advantage over conventional clinical staging. High percentages of thymic carcinomas and thymic carcinoids were in Stage IVB, and the TNM classification of these tumors was considered to be more useful. PMID- 1913547 TI - Clinical significance of morphologic subdivision in diffuse large cell lymphoma. AB - Although diffuse large cell lymphomas can be morphologically divided into large cell (DLC) and immunoblastic (IBL) subtypes, the clinical significance of this subdivision remains controversial. The initial diagnostic materials from 85 patients with recorded diagnoses of diffuse large cell lymphoma who were treated at Stanford between 1975 and 1986 with cyclophosphamide, doxorubicin (Adriamycin; Adria Laboratories, Columbus, OH), vincristine, and prednisone (CHOP); methotrexate, bleomycin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone (M-BACOD); or methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B) chemotherapy were retrospectively reviewed by a panel of hematopathologists and classified according to morphologic criteria of the Working Formulation. Based on the criterion of agreement of two of three observers, 60 patients were classified as having DLC, 19 as having IBL, and the lymphomas in 6 patients could not be additionally classified. No significant differences in complete response (CR) rate, freedom from disease progression (FFP), or overall survival were found between the DLC and IBL groups. There was also no significant difference in prognosis between DLC cases additionally subclassified as large cleaved cell (16 patients) and those with large non-cleaved cell (36 patients). Although IBL is considered to be a high-grade lymphoma, the authors concluded that it does not differ significantly in prognosis from DLC lymphoma and, therefore, does not justify a modified treatment selection based on IBL morphologic type alone. Definitive evaluation of the prognostic significance of morphologic subdivision may require a larger cohort of uniformly treated patients. PMID- 1913548 TI - A multivariate study of the prognosis of oral squamous cell carcinomas. Are blood group and hemoglobin new prognostic factors? AB - Because blood groups and hemoglobin concentration have been associated with the risk of the development of some cancers, this study evaluated the significance of ABO and Rhesus blood groups and hemoglobin concentration as prognostic factors in oral squamous cell carcinoma (SCC). The authors examined all registered primary SCC of buccal and maxillary alveolar mucosa in the Norwegian population between 1963 and 1972. The biopsy specimens from these patients were reevaluated and borderline cases excluded. The remaining 111 cases were included in the study, and features recorded on first admission were included in the survival analyses. ABO and Rhesus blood groups were found in 99 of these patients. Multivariate survival analysis showed that tumor size, hemoglobin concentration, stage, and Rhesus blood groups were significant prognostic factors, but sex, age, treatment, duration of symptoms, ABO blood groups, and clinical appearance of the tumors were not. The prognostic value of Rhesus blood groups and hemoglobin concentration has not been previously reported for oral SCC. PMID- 1913549 TI - Primary extracranial neuroblastoma with central nervous system metastases characterization by clinicopathologic findings and neuroimaging. AB - The authors report the clinicopathologic and neuroimaging findings in ten children with primary abdominal or thoracic neuroblastoma who relapsed in the central nervous system (CNS) without evidence of concurrent intracranial extension from adjacent bone, dura, or dural sinus metastases. At diagnosis, the patients ranged in age from 0.3 to 4.5 years (median, 2 years). Their times to CNS relapse ranged from 2 to 34 months from diagnosis. In seven patients the relapse occurred from 1 to 14 months after elective discontinuation of therapy. In four patients, the CNS relapse was the primary (isolated) adverse event. Four patients could not be treated at the time of relapse, and they died within 7 days of progressive CNS disease. In the remaining group, craniospinal irradiation with or without administration of a platinum compound and an epipodophyllotoxin caused complete CNS remissions lasting 4, 5, 16, and 62+ months. Neuroimaging and autopsy findings indicated that cerebrospinal fluid is the major pathway for neuraxis dissemination by neuroblastoma cells. There was no evidence of dural penetration in any patient. The possibility of relapse in the neuraxis should be considered for any patient with neuroblastoma who had neurologic deterioration. A combination of craniospinal radiation and administration of a platinum compound and an epipodophyllotoxin will induce complete responses in some patients with neuraxis involvement by neuroblastoma, but the risk of subsequent failure outside the CNS remains high. PMID- 1913550 TI - Mammographically guided fine-needle aspiration biopsy of nonpalpable breast lesions. Can it replace open biopsy? AB - The authors report the accuracy of mammographically guided fine-needle aspiration (FNA) for the diagnosis of nonpalpable breast lesions in a series of 71 patients. Each mammographically guided FNA was immediately followed by hookwire localization and open biopsy. Seven malignancies were identified cytologically, but three cancers were not detected in aspirates judged to be sufficient for diagnosis. In addition, 19 aspirates were reported to be insufficient, and 4 of these were obtained from lesions histologically proven to be adenocarcinoma. Although no false-positive diagnoses were encountered, the technique demonstrated a sensitivity of 78% and a diagnostic accuracy of 94% for adequate specimens. In this study, mammographically guided FNA was insufficiently sensitive to replace open biopsy for the diagnosis of nonpalpable breast lesions. PMID- 1913551 TI - Stage IE primary malignant lymphomas of the uterine cervix. AB - The experience of the authors with primary non-Hodgkin's lymphoma of the uterine cervix from 1980 to 1986 included five Ann Arbor Stage IE cases successfully managed by meticulous staging and radiation therapy. The clinicopathologic features of the patients are described and compared with 38 previously reported Stage IE cases. When all 43 patients were evaluated, the median age was 40 years of age (range, 20 to 80 years of age) and 77% were premenopausal. Most patients (74%) reported abnormal vaginal bleeding, although approximately 20% were asymptomatic. The primary cervical tumors were typically of large size, with half exceeding 4 cm in diameter. Using the International Federation of Gynecology and Obstetrics (FIGO) system for staging cervical cancer, stage distribution was 44% Stage I, 42% Stage II, 12% Stage III, and 2% Stage IV. Histologically, approximately 70% were of the diffuse, large cell type (Working Formulation). External beam radiation therapy supplemented by brachytherapy or hysterectomy was used for 76% of the patients reviewed. There was only one treatment failure among the 28 patients whose treatment included radiation and whose cases were followed for at least 2 years. This experience and a review of the literature indicate that most cases of primary lymphoma of the uterine cervix are Ann Arbor Stage IE, and can be cured with traditional combinations of surgery and radiation therapy after careful evaluation. PMID- 1913552 TI - Different genomic and metabolic patterns between mass screening-positive and mass screening-negative later-presenting neuroblastomas. AB - The mass screening of neuroblastoma has been undertaken in Japan by measuring urinary vanillylmandelic acid (VMA) and homovanillic acid (HVA) in all infants at the age of 6 months. This program may not only improve the prognosis but also provide important insights into the biology and evolution of human neuroblastoma. The authors studied and discuss the clinical significance of the N-myc oncogene, catecholamine metabolism, and other tumor markers in 43 patients with neuroblastoma who underwent the urinary screening test at 6 months of age. Thirty patients were found by the screening, and 13 were negative at the screening but later had a tumor. In the former group, the tumors were mostly in early stages (Stage I, 12; Stage II, 11; Stage III, seven), no amplification of N-myc was observed, and all patients are alive without disease. Although two patients whose urine at the screening showed elevated VMA and HVA levels and accidentally were not treated for 13 and 17 months, there was no change in the values of VMA and HVA during that time. However, in the latter group, the tumors were mostly in advanced stages (Stage I, one; Stage III, four; Stage IV, eight) and N-myc amplification was observed in seven of 13. Only two of these 13 are alive without disease. The age at diagnosis of the screening-negative group was 23 months compared with 8 months in the patients identified by screening, and the pattern of catecholamine metabolites in the screening-negative group tended to be dopaminergic with a low VMA-HVA ratio, especially in cases with N-myc amplification. These data suggest that the screening-positive patients with neuroblastoma may have favorable characteristics, and the biology of these tumors may be different from that of screening-negative later-presenting tumors. They also suggest that there may be at least two distinct subsets of neuroblastoma. For the early detection of the poor prognostic neuroblastomas, the measurement of urinary dopamine with VMA and HVA at later ages, such as 1 to 2 years, should be considered. PMID- 1913553 TI - Prognostic indicators of metastatic bone disease in human breast cancer. AB - The time to detection of metastatic bone disease (MBD) by radiographic examination was studied in 221 patients with advanced breast cancer. None of the patients had bone metastases by radiography or bone marrow carcinosis, evaluated by bilateral iliac crest biopsy. The period of follow-up after first recurrence was 46 months. Fifty-five patients (25%) had MBD; 89 patients died without MBD. The cumulated rate of MBD was 14% and 27% after 1 and 2 years, respectively. The actuarial time to MBD was associated significantly with the presence of positive regional lymph nodes at primary diagnosis, the occurrence of metastases in the mediastinum, and the presence of visceral metastases. Moreover, a positive bone scintigraphic scan at the time of first recurrence and abnormal biochemical analyses from serum also were associated significantly with a shortened time to MBD. Micrometastases in the bone marrow, as detected by monoclonal antibodies against epithelial markers (epithelial membrane antigen and cytokeratin), were present in 18% of the patients. The presence of such tumor cells was not associated with development of radiologic MBD. Cox analyses revealed that the result of bone scintigraphic scanning and the presence of visceral metastases were the most important and independent predictors of the time of MBD. Four distinct prognostic groups were identified based on the status of these two variables. The recognition of these prognostic groups has several implications for clinical and therapeutic management of patients with recurrent breast cancer. PMID- 1913554 TI - Nephrogenic diabetes insipidus. An unusual presentation of recurrent rectal cancer. AB - The occurrence of diabetes insipidus (DI) in patients with systemic cancer is caused usually by tumor metastasis to the hypothalamus or posterior pituitary. A 43-year-old man with DI 8 months after radical surgery for a poorly differentiated adenocarcinoma of the distal rectum is reported. A therapeutic trial of intranasal desmopressin acetate did not correct the hyposthenuria, thus localizing the defect to the kidneys. A large tumor recurrence in the pelvis caused bilateral hydroureteronephrosis, resulting in nephrogenic DI. This report shows that not all cases of DI in cancer patients are of central origin. PMID- 1913555 TI - Delay in the diagnosis of cutaneous malignant melanoma. A prospective study in 250 patients. AB - The extent and consequence of patient and professional delay in the diagnosis and treatment of 250 consecutive patients with primary cutaneous malignant melanoma was investigated. Mean total delay from the onset of observed change in a melanoma to appropriate therapy was 11.1 months. The major component of delay (9.8 months) was patient related. Seventy-nine (31.6%) patients waited more than 6 months before seeking medical attention. Few patients recognized early melanoma, and 46% responded only to late features (i.e., ulceration or bleeding). Inappropriate professional delay (misdiagnosis or observation without specific action) occurred in 30 consultations (12.4%) and resulted in a further 1.3-month mean delay in treatment. No correlation (r = 0.027) was found between delay in diagnosis and thickness of melanoma for the study population overall. A significant relationship (r = 0.2087; P less than 0.05) was found between longer lag time and advanced disease in 92 patients with nodular melanoma. Asymptomatic melanomas incidentally diagnosed during routine skin surveillance were significantly more favorable (mean depth, 0.89 mm) than symptomatic melanoma (1.76 mm; P less than 0.01). These data suggest that future public education campaigns should emphasize early signs of melanoma and that professional programs should stress routine skin surveillance and prompt referral of suspicious lesions for diagnostic biopsy. PMID- 1913556 TI - The association of breast cancer and colorectal cancer in men. An analysis of surveillance, epidemiology, and end results program data. AB - There is a known increased risk for the co-occurrence of both breast cancer and colorectal cancer in the same women, presumably as a result of either shared reproductive hormonal or environmental risk factors. Using data from the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute, the authors investigated whether there is a similar relationship between breast cancer, colorectal cancer, and prostate cancer in men. The observed-expected ratio was not significantly elevated for either colorectal cancer after breast cancer or for breast cancer after colorectal cancer in men. There was an increased incidence of prostate cancer after colorectal cancer, but this relationship was not present in the opposite direction and is believed to result from detection bias. There was an increased incidence of breast and colorectal cancer in women. These results suggest that the observed breast and colorectal cancer relationship in women may be a result of shared reproductive hormonal factors. PMID- 1913557 TI - Survival among patients with clinical stage I cutaneous malignant melanoma diagnosed in Western Australia in 1975/1976 and 1980/1981. AB - Five-year survival rates were slightly higher for patients with cutaneous malignant melanoma (CMM) diagnosed in Western Australia in 1980/1981 (89% in men and 95% in women) than in those whose melanomas were diagnosed in 1975/1976 (88% in men and 91% in women). The improvement in survival was probably due to a decrease in median tumor thickness from 1.29 mm in 1975/1976 to 0.77 mm in 1980/1981 because tumor thickness was the most important histologic index of prognosis. Tumor cell type and cross-sectional profile were the only other histologic characteristics that independently influenced fatality rates. Prognosis was significantly worse in males than in females and in patients with tumors on the posterior head and neck. Ten-year survival rates of patients whose melanomas were diagnosed in 1975/1976 was 82% in men and 87% in women, indicating that these patients continued to experience some excess mortality up to 10 years after diagnosis. The comparatively small improvement in prognosis in the 5-year period between these two groups suggests that survival might be expected to continue to improve only gradually unless there is a sharp absolute decrease in the number of thick tumors diagnosed. PMID- 1913558 TI - Cancer survival in Estonia from 1978 to 1987. AB - On the basis of the Estonian Cancer Registry's data bank, survival was examined for 36,020 incident cancer cases diagnosed from 1978 to 1987 in men and women residing Estonia. The number of cases, the proportion of cases with microscopic verification, the observed and relative 5-year survival rates, and the median survival time were determined for 25 most common cancer sites and all sites combined. The highest relative survival rates were documented for cancers of the lip, corpus uteri, and skin (melanoma, women). The lowest rates were found for acute myeloid leukemia (women), and cancers of the liver, pancreas, and esophagus (men). For most cancer sites, the survival rates of women exceeded those of men. The comparison of nationwide survival rates by selected sites in Estonia with those in Finland revealed that Estonian rates were lower. Existing information shows that the Estonian Cancer Registry has relatively good data resources for promoting more sophisticated survival studies. PMID- 1913559 TI - Autobodies in neoplasia. PMID- 1913560 TI - Picture archiving and communication systems. PMID- 1913561 TI - Automatic acquisition interfaces for computed radiography, CT, MR, US, and laser scanner. AB - Existing radiological imaging devices such as computed radiography (CR), computed tomography (CT), magnetic resonance imaging (MR), and ultrasound (US) systems generally do not have a direct digital interface to an external computer. Thus, special developments are necessary for their integration into a Picture Archiving and Communication System (PACS). The interface architecture and software models for performing automatic data acquisition from these devices as well as a CR plate scanner and a laser film digitizer are discussed based on their networking capabilities and the accessibility of internal data structures. The design approaches and operation efficiencies vary drastically depending on whether additional modules are needed, and whether the acquisition is performed on-line or off-line. In addition to the image data link, a complete acquisition interface includes polling of text patient information, image reformatting to the UCLA standard, and communication to the archival database. PMID- 1913562 TI - PACS workstation design. AB - This paper covers some of the recent concepts in designing a digital imaging workstation in a multimodality Picture Archiving and Communications Systems (PACS) network. A workstation in a multimodality PACS network must access, display, and analyze digital images from different imaging modalities with very different formats. The user interface should allow clinicians with minimal or no computer manipulation skills to use complex analysis tools. General guidelines of a graphics oriented user interface, based on windows and icons, are proposed. Instantaneous (real-time) response in the primary display and processing functions is vital for user acceptance. The hardware architectural concepts to achieve such a performance speed are described. Finally, a workstation environment conducive to comfortable viewing by the radiologists is discussed. PMID- 1913563 TI - HIS, RIS, and PACS. AB - In this paper the historical background of the concepts Hospital Information System, Radiology Information System, and Picture Archiving and Communication System (HIS, RIS, PACS) is presented. Next the present situation of the realization of the concepts is considered; the conceptual relation between the three is discussed. Accepting the existence of the three concepts, first the relation between HIS and RIS is analysed, next the relation between PACS and HIS/RIS is considered. It is concluded that such a relation is vital for the realization of a full-scale PACS. Moreover, it is concluded that not only data has to be exchanged but also information. The need for a generic description of an interface between the two is emphasized. PMID- 1913564 TI - Picture archiving and communication system (PACS) networking: three implementation strategies. AB - This paper outlines the diverse Picture Archiving and Communication Systems (PACS) networking implementation strategies at the University of California at Los Angeles, the University of Florida, and the University of Kansas. At the University of California at Los Angeles, a very high-speed network has been integrated into a hierarchical networking strategy, resulting in an entirely customized network for the local transmission of images. The University of Florida has chosen to implement networks for local transmission of images using commercially available equipment. The University of Kansas, specializing in teleradiology applications, uses commercial telecommunication circuits to implement long distance referral services to small hospitals. PMID- 1913565 TI - PACS database architecture and design. AB - PACS (Picture Archiving and Communication Systems) database design requires careful understanding of the data and processing needs of radiologists, referring physicians, radiology staff, administrators, and researchers. Due to access requirements, the physical implementation for the management of small text data sets differs from the implementation strategy for large image data sets (centralized vs. distributed storage strategies). In this paper we discuss the database structure, storage architecture, file placement strategies, and administration considerations of the UCLA PACS. PMID- 1913566 TI - Systems integration for PACS. AB - A successful PACS (Picture Archiving and Communications System) implementation requires an eclectic integration of a number of key technologies. Among these are equipment interfaces, communications, storage, and display. Coincident with this, the software architecture must support a distributed system of heterogeneous structures, provide for protocol and format conversions to a unified system standard, be scalable to accommodate expansion, and provide a measure of fault tolerance. In this paper we survey the current state of the UCLA PACS components and architecture. PMID- 1913567 TI - PACS clinical experience at Georgetown University. AB - Georgetown University Hospital has been operating an image management and communications system (IMACS or PACS) for three-and-a-half years. This work was initially funded under the Army Medical Research and Development Command Digital Imaging Network Systems (DINS) project. The system was taken from a research system supporting only radiology tasks to one extended to clinical use, and has been used in clinical work for two-and-a-half years. This paper will summarize our PACS clinical experience and will describe the operational features implemented and those still necessary. PMID- 1913568 TI - Clinical experience--16 months of HU-PACS. AB - Sixteen months experience with HU-PACS (Hokkaido University PACS) is reported. This report describes the hardware and software aspects of HU-PACS in its working state. Evaluation of the system is also reported, and usefulness of PACS concludes paper. PMID- 1913569 TI - Clinical experience with PACS at the University of Pennsylvania. AB - A Picture Archiving and Communication System (PACS) was installed in the Medical Intensive Care Unit of the Hospital of the University of Pennsylvania. For one year, 8 week periods of FILM ONLY usage were alternated with 8 week periods of PACS OR FILM usage. The time interval between obtaining portable chest images and taking image dependent actions decreased when the PACS was used, however, about 40% of the action decisions were made without a radiologist's consultation. Only 5% of action decisions were made without consultation during the FILM ONLY periods. A new clinical study for measuring diagnostic accuracy and efficiency as well as communication patterns is described. PMID- 1913570 TI - PACS--clinical experience at UCLA. AB - Implementation of picture archiving communication systems (PACS) at UCLA began with the evaluation of the systems in Pediatric Radiology, one of the 11 sections of the Department and the Coronary Care Unit, one of the 14 ICU's in the Hospital. We have now completed PACS development for all CT's and MR's which allows communication between a newly developed outpatient facility, the hospital, and the remote research facility in addition to Pediatric Radiology and the Coronary Care Unit. The following are some of the advantages of PACS from a clinical standpoint: (a) Conferences with clinicians have been more effective by spending more time on each case, but less total time for each conference; (b) Clinicians are satisfied with PACS at the remote site, but it is clear that the radiologists' interpretation must accompany the images; (c) PACS allows for the development of interactive teaching of the students; (d) PACS allows for a new method of radiology practice by analyzing the image and providing a more comprehensive, quantitative consultation, otherwise not possible with analog systems. PMID- 1913571 TI - Image analysis and quantification of atherosclerosis using MRI. AB - This paper describes an image processing, pattern recognition, and computer graphics system for the noninvasive identification and evaluation of atherosclerosis using multidimensional Magnetic Resonance Imaging (MRI). Particular emphasis has been placed on the problem of developing a pattern recognition system for noninvasively identifying the different plaque classes involved in atherosclerosis using minimal a priori information. This pattern recognition technique involves an extension of the ISODATA clustering algorithm to include an information theoretic criterion (Consistent Akaike Information Criterion) to provide a measure of the fit of the cluster composition at a particular iteration to the actual data. A rapid 3-D display system is also described for the simultaneous display of multiple data classes resulting from the tissue identification process. This work demonstrates the feasibility of developing a "high information content" display which will aid in the diagnosis and analysis of the atherosclerotic disease process. Such capability will permit detailed and quantitative studies to assess the effectiveness of therapies, such as drug, exercise, and dietary regimens. PMID- 1913572 TI - Validation of magnetic resonance imaging (MRI) multispectral tissue classification. AB - The application of NASA multispectral image processing technology for analysis of Magnetic Resonance Imaging (MRI) scans has been studied. Software and hardware capability has been developed, and a statistical evaluation of multispectral analysis application to MRI scans of the head has been performed. PMID- 1913573 TI - Observations on the choice of reconstruction matrix in magnetic resonance imaging. AB - This paper points out a number of ways in which the choice of imaging matrix can affect the performance of a machine in Magnetic resonance imaging. It observes that, contrary to most other techniques, there are advantages in some instances both in sensitivity and detectability through the use of lower resolution images which may not be obtainable in higher resolution ones--although it is equally true that there are other circumstances where the reverse is true. Considerations of effects arising from field inhomogeneity, patient motion, susceptibility mapping, and fluid flow are used to illustrate the argument. PMID- 1913574 TI - Automatic segmentation of head MRI images by knowledge guided thresholding. AB - In this paper we present a procedure which automatically extracts soft-tissue from multi-sliced head MRI images, and then displays three-dimensional shapes of the extracted soft-tissues. We use an iterative thresholding algorithm for segmentation in which an optimum threshold value is decided based on a goodness measure we proposed. This procedure can be used in a preliminary diagnosis in brain surgery without much effort of users, because of whole procedure including threshold selection and segmentation is performed automatically for rendering a three-dimensional image of soft-tissue's surface on a graphic terminal. PMID- 1913575 TI - 3-D heart image reconstructed from MRI data. AB - The gated MRI method gives us several sets of cross-sectional images on transverse, coronal, and sagittal planes of the heart in a cardiac cycle. In this paper, a method to reconstruct 3-D shapes of each part of the heart (i.e., left ventricle, left atrium, right ventricle, right atrium, aorta, and pulmonary artery), in a voxel space using these sets of cross-sectional images is proposed. The whole heart image composed of these six parts properly put together can be superimposed on the original cross-sectional images for display purposes. PMID- 1913576 TI - Evaluation of methods for shaded surface display of CT volumes. AB - There are several ways to compute a shaded surface display of radiological 3D density volumes. In this paper we evaluate 12 methods which are different combinations of principles for detection of the surface to be displayed (gray value threshold, gradient threshold, zero-crossing of 2nd derivative), localizing this surface in space (grid-point accuracy, subvoxel accuracy) and finally estimating the direction of the surface normal (from the gradient in the 2D depth image, from the gradient in the 3D-volume). The best quality is obtained by zero crossing detection, subvoxel localization, and 3D-gradient orientation. PMID- 1913577 TI - The tracking of boundaries in multidimensional medical images. AB - We became interested in the problems associated with boundary tracking in multidimensional spaces due to our involvement in medical imaging. We give as background our motivation from medicine. We define objects and their surfaces in discrete three-dimensional space and the state of the art in three-dimensional boundary tracking. Discussed are generalizations, conjectures, and open problems. Finally, we discuss what seems to us a suitable mathematical framework for future research in this area. PMID- 1913578 TI - Automated surface interpolation technique for 3-D object reconstruction from serial cross sections. AB - A method for automatically reconstructing a three-dimensional object from serial cross-sections is presented in this paper. The method combines the techniques of dynamic elastic contour interpolation, spline theory, and quadratic-variation based surface interpolation. In the proposed method, the initial description of the object is formed by applying the elastic interpolation algorithm to generate a series of intermediate contours between each pair of consecutive cross sections. After this, a preliminary processing for surface computation is carried out by mapping the contours into the domain of surface function and then using spline functions to calculate the initial surface values. Based on the output from the preliminary processing, we apply the quadratic-variation-based surface interpolation algorithm to calculate the final surface representation. Since our method takes the continuity of high order derivatives into consideration, the smooth and complete surface of a 3-D object can thus be reconstructed. PMID- 1913579 TI - Information preserving image compression for archiving NMR images. AB - This paper presents a result on information preserving compression of NMR images for the archiving purpose. Both Lynch-Davisson coding and linear predictive coding have been studied. For NMR images of 256 x 256 x 12 resolution, the Lynch Davisson coding with a block size of 64 as applied to prediction error sequences in the Gray code bit planes of each image gave an average compression ratio of 2.3:1 for 14 testing images. The predictive coding with a third order linear predictor and the Huffman encoding of the prediction error gave an average compression ratio of 3.1:1 for 54 images under test, while the maximum compression ratio achieved was 3.8:1. This result is one step further toward the improvement, albeit small, of the information preserving image compression for medical applications. PMID- 1913580 TI - The spermatozoon of the Chinese bitterling, Rhodeus sericeus sinensis (Cyprinidae, Teleostei). AB - The bitterling spermatozoon has been examined by electron microscopy using sectioned material and freeze-fracture replicas. Its structure is characterized by a higher degree of order than is seen in spermatozoa of related teleosts. The intramembrane particles in the cell membrane are arranged in a large (around 1 micron in diameter) hexagonal grating pattern at a certain site of the sperm head. The flagellum protrudes from a site slightly posteriorly to this hexagonal grating and is surrounded by a cytoplasmic sleeve that contains regularly spaced filaments in a helical arrangement. The sperm midpiece contains a large mitochondrion enclosed in an elaborate system of membranous cisternae and narrow tubules. Fertilization in the bitterling takes place in the gill chamber of freshwater mussels--a unique brood chamber and site of fertilization for a vertebrate. PMID- 1913581 TI - Axonal microtubules: comparative anatomy in vertebrates, including man. AB - The microtubular density was assessed with the electron microscope in 3 microns myelinated fibers, myelin excluded, of 11 species from the following classes: Osteichthyes, Amphibia, Reptilia, Aves, and Mammalia. The average for all species was 20.6 microtubules/microns 2. Dispersion of values was restricted as shown by a coefficient of variation of 15.8. The microtubular content of nonmedullated axons was assessed in trout, lizard, finch, and man. In the four species, the number of microtubules increased with the cross sectional area of the axon. In trout, lizard and finch, the microtubular density decreased from over 100 microtubules/microns 2 in fibers smaller than 0.1 micron 2 to about 30 in 1 micron 2 fibers; in axons of equal size, the packing of microtubules of nonmedullated was similar between them, and with reported values for peripheral axons of cat and rat. In man, the microtubular density of nonmedullated fibers exhibited only a mild decrease with the axonal size. In the finch, myelinated and nonmedullated axons overlapped in the range 0.23-0.60 micron 2 and both groups exhibited similar microtubular densities. We conclude that the packing of microtubules of the vertebrate peripheral axon is a feature largely conserved during evolution. PMID- 1913582 TI - A comparison of the atomic composition of siderosomes (haemosiderin) in cryosections of unfixed frozen tissues and Epon-embedded tissues. AB - Siderosomes (i.e. single membrane-bound lysosomal bodies containing haemosiderin) were produced in the liver and muscle of rats by injections of iron dextran. Electron-probe X-ray analysis was executed on siderosomes in cryosections of quick-frozen fresh unfixed tissues (liver and muscle) and sections of Epon embedded tissues. There were no statistically significant differences between the ratios of iron:phosphorus and iron:sulphur in these two types of preparations. Hence it is concluded that there is no significant loss or gain of phosphorus or sulphur during preparation of tissues for Epon embedding. The results confirm past belief that so little phosphorus or sulphur is present in siderosomes that haemosiderin is best regarded as ferric hydroxide oxide. A new finding in the present study was the demonstration of small amounts of potassium in siderosomes in cryosections. It seems that potassium is lost (leaches out) from siderosomes during preparation of tissues for Epon-embedding. PMID- 1913583 TI - Immunocytochemical localization of xanthine oxidase in rat myocardium. AB - Monoclonal antibodies (MAb's) to xanthine oxidase (XO) (from bovine milk) were produced by hybridoma technique. Culture supernatants were initially screened using enzyme-linked immunoabsorbant assay (ELISA). Forty four positive clones were subcloned and further characterized by ELISA and immunoblot analysis. Out of fifteen clones, which were positive in immunoblot analysis, one clone N2-26 was also positive in immunocytochemical studies. Indirect immunoperoxidase and enzyme histochemistry staining showed that XO activity is present in endothelial cells of capillaries, small blood vessels and also in interstitial cells. Electron microscopy revealed that diaminobenzidine reaction product was distributed in the cytoplasm of interstitial cells and endothelial cells of capillaries and small blood vessels. This is the first report of the presence of XO in interstitial cells and endothelial cells of small blood vessels. Allopurinol, which inhibits the xanthine oxidase activity, did not have any effect on the immunocytochemical staining. Our results in normal rat heart suggest that XO activity is confined to interstitial cells, endothelial cells of capillaries and small blood vessels. PMID- 1913584 TI - Ovarian microvasculature in normal and hCG stimulated rabbits. A study of vascular corrosion casts with particular regard to the interstitium. AB - The microvasculature of rabbit ovaries, with special regard to the interstitial stromal tissue, was studied by scanning electron microscopy (SEM) of vascular corrosion casts. The casting medium (Mercox) was injected in normal animals and in animals in which ovulation was induced by 100 I.U. of human chorionic gonadotropin (hCG) i.v. Vascular baskets of different size and architecture related to follicles in various developmental stages were observed in the ovarian cortex. Small (primary) follicles showed thin and thready capillaries. Larger (secondary and antral) follicles showed a progressive increase in number, size and tortuosity of round-meshed capillaries, related to adaptation of the growing follicle to the approaching ovulation. Capillary sprouts, due to the enhanced angiogenesis of growing follicles, were seen. These aspects were more evident in ovulatory follicles. In addition, numerous resin leakages, due to the increased permeability of the sinusoidal net, were seen in the cavities of ovulatory follicles. Interstitial-stromal tissue capillaries were diffusely distributed in the cortex among the follicular baskets. Their morphology remained unchanged after hCG stimulus. In the periphery of the cortex, the microvascular net showed large (70-90 microns) irregularly rounded meshes, with thin, thready capillaries often anastomosed with those of primary follicles. Inner cortex capillaries were thin, thready and arranged in polygonal meshes of 40-70 microns. The arrangement and the distribution of the interstitial-stromal capillaries may have some special role during the cyclic activity of the ovary.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1913585 TI - Scanning electron microscopic observations on muscle cells of experimental mitochondrial myopathy produced by 2, 4-dinitrophenol. AB - The morphological changes of the skeletal muscle cells of the rat experimental myopathy induced by 2, 4-dinitrophenol were examined by scanning electron microscopy in comparison with the ultrastructure of normal muscle cells. Specimens were prepared by the Aldehyde-Osmium-DMSO-Osmium method which permits the three-dimensional demonstration of intracellular structures under SEM. In the specimen prepared by the method, myofibrils having been completely dissolved, intracellular membranous structures such as the sarcoplasmic reticulum, T-tubules and mitochondria were clearly demonstrated in three dimensions. In the experimental mitochondrial myopathy, large accumulations of mitochondria were observed at the subsarcolemmal region. Mitochondria in the perinuclear and intermyofibrillar region showed swelling and occasionally accompanied abnormal concentric cristae. The sarcoplasmic reticulum which showed regular network in normal muscle cells entirely disappeared in the mitochondrial myopathy. Although the mitochondrial changes obtained in this study were almost identical to those previously reported by transmission electron microscopy, the changes in the sarcoplasmic reticulum have not been described in previous works. PMID- 1913586 TI - The fine structure of testicular interstitial cells in the mouse. A comparison after conventional double fixation versus rapid freezing followed by freeze substitution. AB - The interstitial cells in the testis of the mouse have been studied both after conventional double fixation with glutaraldehyde followed by osmium tetroxide and after rapid freezing and cryosubstitution with osmium tetroxide-acetone by light, scanning and transmission electron microscopy. Differences have been found especially concerning the preservation of lipids and the appearance of mitochondria. Varying proportions and different aspects of rough and smooth endoplasmic reticulum were observed corresponding after both preparation methods thus confirming their real existence. Numerous specific contacts are found between macrophages and Leydig cells, indicating a functional interdependence between these two cell types. Though structural preservation is superior after freeze substitution in the outermost zone, artifacts caused by the initial impact, by ice crystal formation, and during substitution must be considered. PMID- 1913587 TI - Increased osmiophilia of glycosaminoglycan-like structures after fixation with cetylpyridinium chloride in human colonic mucosa. AB - The effects on tissue ultrastructural appearance of fixation with cetylpyridinium chloride (CPC)-additioned formaldehyde were studied at the ultrastructural level in human colonic mucosa. We found that CPC did not impair tissue morphology and induced a remarkable osmiophilia in glycosamino-glycan-like structures, which did not require further staining. PMID- 1913588 TI - Morphogenesis of the secondary envelope of the oocyte in a teleostean fish of the family Cyprinodontidae: Aphyosemion splendopleure. AB - The follicular epithelium of the oocyte in Aphyosemion splendopleure is made up of prismatic cells in which the density of the cytoplasm is variable. At the end of vitellogenesis the follicular cells show polarity. The rough endoplasmic reticulum is localized in the cytoplasm situated between the nucleus and the basal lamina. This reticulum splits up into vesicles limited by a membrane covered with ribosomes. At the beginning of postvitellogenesis the Golgi apparatus produces numerous secretion granules in the cytoplasmic region contiguous to the surface of the oocyte. These Golgi elements, together with amorphous material whose origin we have not been able to define, form the secondary envelope of the egg. This envelope is made up of two layers: an inner layer formed by an agglomeration with a membranous aspect and a superficial layer made up of tubular elements. The superficial layer forms an ornamentation clearly shown up by scanning electron microscopy. PMID- 1913589 TI - Ultrastructural studies on dermis from prolidase deficient subjects. AB - Ultrastructural analyses were performed on clinically normal skin from forearm and/or femoral regions of five subjects, all excreting high levels of gly-pro dipeptides into the urine and exhibiting very low prolidase activity on hemolyzed erythrocytes. In both regions, the overall organization of the dermis was normal. Stereological analysis, however, showed that collagen volume density was reduced when compared to that of age-matched controls. Collagen fibrils did not show ultrastructural alterations, but they were distributed into a higher number of small bundles, and their diameters shifted towards lower values compared to age matched controls. The elastin volume density was slightly reduced in the patients, especially in the femoral areas. In both forearm and femoral dermis, elastin fibers were significantly more numerous and smaller than in controls. Furthermore, elastin fibers were apparently normal in the forearm dermis, whereas appeared polymorphic and cribriform in the femoral skin. The results focused on the importance of efficient proline re-utilization for normal collagen and elastin synthesis and deposition. The differences between femoral and forearm skin regions from both clinical and ultrastructural points of view, may depend on mechanisms that regulate circulation and, possibly, on other factors which modulate the phenotypic expression of mesenchymal cells. PMID- 1913590 TI - Rickettsiae and giant lysosomes in the testes of Temnocephala novaezealandiae (Platyhelminthes: Temnocephaloidea). AB - Rickettsiae are concentrated in the testes of Temnocephala novaezealandiae, where they occupy the cytoplasm of spermatogenetic stages and the testis epithelia. They have gram negative ultrastructural characteristics and are surrounded by clear zones which are not membrane-limited; indented mitochondria are associated with the clear zones. Propagation occurs by simple division. Extensions of the testis epithelium envelop cloned groups of spermatocytes, spermatids and spermatozoa. Heterophagosomes isolating unmodified rickettsiae, and giant lysosomes enclosing bacteria in advanced stages of degradation, are contained within the epithelial processes. Rickettsiae and large lysosomes were found also in testes of Troglocaridicola mrazeki, a scutariellid. Peririckettsial lucid zones are interpreted as areas of histopathy where host cytoplasm has been catabolized by bacterial enzymes. The rickettsiae evidently are true parasites, although they have no apparent harmful effect on the general condition of their hosts. Digestion of bacteria in lysosomes may provide nutrients for spermatogenetic stages. Transmission of rickettsiae to juvenile temnocephalids does not occur via the spermatozoa. PMID- 1913592 TI - Molecular structure of mitochondrial cristae, solid state biochemistry and a simple theory of respiration-phosphorylation coupling. AB - Thanks to the improvement of preparatory procedures in electron microscopy during the 1960's the structural analysis of mitochondria has been extended to the molecular level leading to an almost 40-year-old misconception regarding mitochondrial structure being replaced by a more realistic version of the structure. The following observations are reviewed: 1) There are three different types of membranes in the mitochondria. 2) Geometrically regularly distributed circumscribed respiratory chain domains are surrounded by a continuous tricarboxylic acid cycle domain. 3) The cristae are compact structure with the enzyme molecules in a three-dimensional arrangement. 4) The active sites of most enzyme molecules are buried in the cristae and are exposed to an environment characterized as a biological solid state. 5) A water translocating mechanism removes water from the cristae maintaining a low water activity in the cristae. 6) The cristae are connected to the cytosol directly through proteinaceous pathways extending through the two surface membranes. 7) The matrix communicates with the cytosol by a route through the two surface membranes, bypassing the cristae. 8) The permeability of the inner surface membrane changes with the respiratory state. 9) The inner membrane particles can be made to appear under experimental conditions that prove their appearance to be an artifact. 10) A simple theory of respiration-phosphorylation coupling is proposed based on the solid state of the cristae. The theory agrees with the chemiosmotic theory with respect to the involvement of proton movement as basis for energy transduction, but differs with respect to how protons contribute to transduction. PMID- 1913591 TI - Surface epithelium of the ovary following oral administration of hexachlorobenzene to the monkey. AB - Hexachlorobenzene (HCB) is a toxic and carcinogenic chemical that has been implicated in female reproductive dysfunctions, including destruction of ovarian follicles in primates. The purpose of this study was to determine the effects of HCB on ovary surface epithelium (SE). Gelatin capsules containing HCB mixed with glucose were given to 16 cynomolgus monkeys housed under controlled conditions in dosages of 0.0, 0.1, 1.0, or 10.0 mg/kg body weight daily, for 90 days; the first group served as the control. At necropsy one ovary from each animal was removed, fixed in glutaraldehyde, and processed by conventional methods for examination by transmission electron microscopy. SE from the animals in control group consisted of a single layer of squamous-to-cuboidal cells which possessed microvilli and contained cytoplasm rich in organelles; the nuclei were placed in middle of the cells. Although the types of alteration were similar in the treated groups, the degree of severity increased with increasing dose levels. In the lowest dose group (0.1 mg/kg) tested, stratification of cells was observed in some areas. Many cells were tall columnar, highly irregular in outline, and showed signs of degeneration. The nuclei had migrated toward the apical surface. Cytoplasm contained a large number of lysosomes, and numerous vesicles, which may have been swollen endoplasmic reticulum. In the 10 mg/kg group the affected cells were in advanced stages of degeneration. These observations support the evidence that HCB is a potent reproductive toxicant. Further studies are required to establish the effects of this damage on reproductive performance. PMID- 1913593 TI - Nonlysosomal cytoplasmic degradation. AB - Several types of cytoplasmic and nuclear inclusions represent stages in the process of non-lysosomal cytoplasmic degradation. Nonlysosomal degradation takes place in regions where cytoplasmic components are trapped and not accessible to primary and secondary lysosomes. Such trapping occurs within the lumina of the nuclear envelope and of endoplasmic reticulum in the form of inverted vesicles, within the nucleus, within mitochondria and within cavities formed by the process of topolysis in neutral lipid droplets. The concept of the process of nonlysosomal degradation permits dynamic interpretation of various inclusions as the concept of the process of focal cytoplasmic degration (autophagy) leads to dynamic interpretation of the lysosome. PMID- 1913594 TI - Inversions and tandem translocations involving chromosome 14q11 and 14q32 in T prolymphocytic leukemia and T-cell leukemias in patients with ataxia telangiectasia. AB - Ataxia telangiectasia (AT) and T-prolymphocytic leukemia (T-PLL) have similar chromosome abnormalities. Cytogenetic findings reported in 5 patients with AT who developed T-cell leukemia revealed: inv(14)(q11q32) (1 case), tandem translocations of chromosome 14 with breakpoints at q11 and q32 (3 cases), and int. del(14)(q11q32) (1 case). Additional abnormalities were present in 4 patients of whom two had trisomy for 8q. Of 27 patients with T-PLL but without AT, investigated by us, 17 had inv(14)(q11q32) and 3 had tandem rearrangement of chromosome 14 with breaks at 14q11 and q32; 15 of them also had rearrangements resulting in trisomy 8q. Two of the leukemias supervening on AT had morphology and clinical course suggestive of T-PLL. Two other cases of AT studied by us developed typical T-PLL at a young age (18 and 39 years). T-cell clones carrying an inv(14), tandem t(14;14) and t(X;14) can be present in AT for long periods of time without evolving into leukemia. In T-PLL, inv(14) and t(14;14) always occurs with other chromosome abnormalities. We suggest that these additional chromosome abnormalities may be required for the leukemic transformation of AT. This is supported by one of the two AT cases studied by us in which a long-standing t(X;14) clone evolved with the formation of t(1;14)(p21;q11), t(8;22)(q24;q11) at the time of the development of T-PLL. PMID- 1913595 TI - Isochromosome 21q in hematologic malignancies. Groupe Francais de Cytogenetique Hematologique. AB - Isochromosome(21q) is a rare but non-random karyotypic change in hematologic diseases. We report 15 cases of i(21q) among a large group of cases, in various disorders of both myeloid and lymphoid lineage. This abnormality has been found as the sole chromosome change in two cases, the remaining cases exhibiting more or less complex karyotypes. Finally we discuss the labelling "i(21q)". PMID- 1913596 TI - Trisomy 13q in a case of acute leukemia with lineage inconsistency. AB - A case of acute leukemia has two distinct immature blast lines, lineage inconsistency with CD 4 positivity, and trisomy 13q as the effective cytogenetic abnormality. This case represents another instance of trisomy 13 with acute leukemia developing in a more primitive pluripotent stem cell. PMID- 1913597 TI - Chromosome analysis of 96 uterine leiomyomas. AB - From September 1989 to May 1990, we attempted cytogenetic analysis on 96 uterine leiomyomas removed from 64 women. Of the 90 tumors in which analysis was successful, 59 had a normal karyotype while 31 had clonal abnormalities. The most common aberration (13 tumors) was 7q-, mostly del(7)(q21.2q31.2); in two tumors with +12 and t(12;14) as the primary abnormalities, the 7q- was obviously a secondary change since it was found only in a subclone. A t(12;14)(q14-15;q23-24) was detected in two tumors, complex aberrations involving both 12q14-15 and 14q23 24 were also present in two, and rearrangements of 12q without concomitant 14q changes were seen in another two myomas. Rearrangements of 6p were present in five tumors, and trisomy 12 was found in two. More than one abnormality could be detected in 17 leiomyomas. Evidence of clonal evolution in the form of subclones was found in eight tumors, all of which were cellular and had histologically detectable mitotic activity. In addition to their clonal complexity, these myomas also frequently exhibited clonal telomeric associations (four tumors) and ring chromosome formation (three tumors; twice affecting chromosome 1). Monosomy 22 occurred as a secondary abnormality in three tumors; it, too, may reflect a preferred pathway in the karyotypic evolution of uterine leiomyomas. PMID- 1913598 TI - Genetic activity and fragile sites. PMID- 1913599 TI - Translocation X;12 in mesothelioma. PMID- 1913600 TI - Complex Ph translocations in chronic myeloid leukemia. PMID- 1913601 TI - t(3;14)(q26;q11) associated with megakaryoblastic transformation of chronic myeloid leukemia. PMID- 1913602 TI - Reinterpretation of the breakpoint position of chromosome 18 in t(14;18) PMID- 1913603 TI - Karyotypic variability and evolutionary characteristics of a polymorphous low grade adenocarcinoma in the parotid gland. AB - The chromosomes of a polymorphous low-grade adenocarcinoma originating from a pleomorphic adenoma of the parotid gland were studied. Three successful preparations were performed. A minor fraction of cells showed normal karyotypes and some cells only inconsistent, usually numerical, deviations. The remaining cells constituted an abnormal monoclonal population with an unusual and very extensive karyotypic variability. The origin of most marker chromosomes could be wholly or partly clarified. Five different subclones could be distinguished on basis of different specific marker chromosomes. The characteristics of the marker sets suggested a closely interrelated derivation of the subclones. The results also provide insight as to the influence of random factors and/or differential growth rate on the chromosomal picture observed in in vitro systems. The present chromosomal observations showed no similarities either to the cytogenetical findings in the five previously reported salivary gland adenocarcinomas or to the deviations seen in the single studied case of carcinoma ex-pleomorphic adenoma. PMID- 1913604 TI - A case of myelodysplastic syndrome with abnormal megakaryocytes and ins(8;3)(q24;q21q26). AB - We report a 56-year-old male patient with refractory anemia with excess of blasts in transformation (RAEB-T) who had an ins(8;3)(q24;q21q26) as the sole chromosome abnormality in bone marrow (BM) cells. The findings of disturbed thrombocytopoiesis with numerous micromegakaryocytes suggest that it could be a variant of the classic ins(3;3)(q26;q21q26) described in hematologic malignancies with abnormal thrombopoiesis. PMID- 1913605 TI - del(15)(q11q15) associated with transformation of chronic myelomonocytic leukemia. AB - Nonrandom cytogenetic abnormalities have been described in a variety of human malignancies including myelodysplastic syndromes (MDS). Acquisition of new chromosomal abnormalities may herald onset of a more aggressive disease. We report a patient with chronic myelomonocytic leukemia (CMMoL) who initially had a normal karyotype, but in whom the clonal interstitial deletion of chromosome 15 (q11-q15) was coincident with development of acute myeloid leukemia (AML) one year later. To date, this chromosomal change has not been reported in CMMoL, AML, or any other human malignancy. PMID- 1913606 TI - Normal cytogenetic values for bone marrow based on studies of bone marrow transplant donors. AB - For individuals suspected of having hematologic neoplasms, interpretation of the clinical significance of sporadic cells with chromosome breakage, structural anomalies, aneuploidy, or polyploidy is often difficult. To help resolve this problem, we established normal cytogenetic values for bone marrow (BM) by investigating 219 BM transplant (BMT) donors using standard techniques for chromosome analysis. The donors ranged in age from 2 to 58 years and were studied for 7 years. The constitutional karyotype for two individuals was 47,XXY; one was mos45,X/46,XX, one was mos46,XX/47,XX, + mar, and 215 were normal. Among other statistics, the median and normal ranges (95th percentile) were determined for any kind of chromosome abnormality, autosomal loss, autosomal gain, sex chromosome loss, sex chromosome gain, chromosome breaks or gaps, major structural abnormalities, and polyploidy. The results suggest that random loss of chromosomes is common in cytogenetic preparations of BM, appears to be largely technical and is inversely proportional to chromosome size. Cells with extra chromosomes or with structural abnormalities are rare in normal BM. No specific sporadic structural abnormalities of chromosomes are associated with normal BM. The widely accepted cytogenetic definition for an abnormal clone appears to be valid, with the possible exception of occasional studies involving loss of smaller autosomes. There may be a correlation between loss of the Y chromosome and age of the patient. PMID- 1913607 TI - Chromosome analyses in chronic lymphocytic leukemia and related B-cell neoplasms. AB - Chromosome analyses were performed by routine G-banding in 29 patients with B cell chronic lymphocytic leukemia (B-CLL), six with immunocytoma (IC), three with centroblastic-centrocytic (cb-cc) lymphoma, and one with hairy cell leukemia (HCL). Ages of the patients were between 46 and 81 years (mean, 63 years). 12-O tetradecanoyl-phorbol-13-acetate (TPA) was used as a mitogen to stimulate leukemic B-cells in 72-hour cultures. Twenty-one patients had one or more chromosomal abnormalities; and in 13 patients, they were clonal; 18 patients had a normal karyotype. Seven patients had trisomy 12 (three B-CLL, two IC, two cb-cc lymphoma); two (B-CLL) had it as the sole abnormality. One patient with B-CLL had trisomy 18 as the sole abnormality, and one with IC had trisomy 18 in combination with trisomy 19. One patient with B-CLL had t(1;6)(p36;p21) as a clonal structural abnormality. A t(11;14)(q13;q32) was consistently observed in one patient with cb-cc lymphoma together with inv(1) (p22p36), der(4)t(4;?)(p16;?), del(6)(q13) and other variable changes. One patient with morphologically atypical B-CLL had t(1;11)(p36;q13) together with der(X)t(X;?)(q26;?), der(3)t(3;?)(q29;?), der(8)t(4;8)(q12;q24.1) and additional variable changes. Both patients with these complex karyotypes were in an advanced stage of disease (Binet stage C) and died within 3-6 months after chromosome analysis. PMID- 1913608 TI - Chronic myelomonocytic leukemia: single entity or heterogeneous disorder? A prospective multicenter study of 100 patients. Groupe Francais de Cytogenetique Hematologique. AB - To investigate the prognostic factors in chronic myelomonocytic leukemia (CMMoL), and to determine the importance of cytogenetic abnormalities at diagnosis and during evolution, a multicentric prospective study was established by the Groupe Francais de Cytogenetique Hematologique. One hundred patients were analyzed: 29 had cytogenetic abnormalities, among which the most frequent were +8, -Y, -7/7q-, and 12p-. Transformation into acute leukemia (AL) occurred in 26 patients. At transformation, eight patients had new cytogenetic abnormalities, not different from those described in the chronic phase of this disease. The median survival was 36 months (+/- 20 months, 95%, confidence interval). In multivariate analysis, four factors were associated with shorter survival: anemia less than 10 g/dl, thrombocytopenia less than 100 x 10(9)/L, splenomegaly, and the presence of immature precursors (IMP) in peripheral blood (PB). A very good prognosis subgroup could be identified which included eight patients with myelodysplasia and monocytosis only and none of the four unfavorable prognostic factors. This study confirmed the cytogenetic findings previously described by our group, and its results yielded further prognostic information. It also indicates the heterogeneity of this disease [some patients show clinical and biologic features of myeloproliferative syndromes (MDS, especially karyotypic abnormalities described only in these syndromes), whereas others appear more to have myelodysplasia, shifting from refractory anemia (RA) to CMMoL], and stresses the need for a more precise definition of this entity. PMID- 1913609 TI - Cytogenetic studies of gastric adenocarcinoma. AB - Cytogenetic analyses were performed on a short-term culture of a primary tumor and an established cell line of gastric adenocarcinoma (SC-M1). The former case was near-diploid, and the latter was near-triploid. No common numerical and structural change or breakpoint was found in these cells. Review of the 13 cases of gastric carcinomas so far reported showed that only trisomies 8 and 9 were consistent findings. The Y chromosome, although lost in all the near-triploid cases, was preserved in all of the near-diploid cases. No consistent structural abnormality and breakpoint were identified in this and other studies. PMID- 1913610 TI - Cytogenetic analysis of a multinodular thyroid goiter. AB - Short-term cultures of a collagenase disaggregated multinodular goiter was shown by cytogenetic analysis to have the mosaic karyotype 47,XX, +7/48,XX, +7, +17/49,XX, +7, +10, +17. No cytogenetic data on goiter are available for comparison with the present case. PMID- 1913611 TI - Cytogenetic evaluation of 20 cultured primary prostatic tumors. AB - We report the cytogenetic evaluation of 20 cultured cell strains derived from primary prostatic adenocarcinomas obtained from radical prostatectomies. The majority of the strains contained cells with only normal male karyotypes (46,XY), but cytogenetically abnormal clonal populations were found in five strains. Two of those strains contained aberrations involving the Y chromosome, one with a -Y and one with a +Y. Three strains (one of which also had the XYY karyotype) exhibited cells with double-minute chromosomes and four strains contained near tetraploid cells. PMID- 1913612 TI - Secondary acute non-lymphocytic leukemia with monosomy 7 arising 9 years after acute lymphoblastic leukemia in childhood. AB - We report a case of pediatric acute non-lymphocytic leukemia (ANLL) with monosomy 7 occurring in a child successfully treated for acute lymphoblastic leukemia (ALL) nine years earlier. Acquired monosomy 7 is currently recognized as a distinct therapy-related cytogenetic abnormality which nonrandomly occurs as a late complication of cytotoxic therapy used in the treatment of both malignant and nonmalignant disease. Most commonly, this occurs as a disorder of bone marrow morphology and function characterized as a myelodysplastic syndrome (MDS) or ANLL. This case report emphasizes the need for continued evaluation of long-term survivors of childhood cancer to identify and minimize therapy-related side effects without compromising successful management. PMID- 1913613 TI - Numerical chromosome abnormalities associated with early clinical stages of gynecologic tumors. AB - Cytogenetic data are presented for 12 ovarian, three endometrial, and one fallopian tube tumors. In 15 of these, primary tumors were analyzed and in one ascites was studied. All specimens were obtained at the time of diagnostic surgery. Trisomy for chromosome 7 was detected in three ovarian and one endometrial tumors. In one case, trisomy 7 was the sole cytogenetic abnormality detected. Three of the four patients with trisomy 7 had early stages of adenocarcinoma. The data suggest that numerical chromosome abnormalities may be common in borderline and in less aggressive gynecologic tumors. PMID- 1913614 TI - Topical treatment of malignant and premalignant skin lesions by very low concentrations of a standard mixture (BEC) of solasodine glycosides. AB - A cream formulation containing high concentrations (10%) of a standard mixture of solasodine glycosides (BEC) has been shown to be effective in the treatment of malignant and benign human skin tumours. We now report that a preparation (Curaderm) which contains very low concentrations of BEC (0.005%) is effective in the treatment of keratoses, basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs) of the skin of humans. In an open study, clinical and histological observations indicated that all lesions (56 keratoses, 39 BCCs and 29 SCCs) treated with Curaderm had regressed. A placebo formulation had no effect on a smaller number of treated lesions. Curaderm had no adverse effect on the liver, kidneys or haematopoietic system. PMID- 1913616 TI - Kupffer cell-mediated oxidative stress on colon cancer cell line visualized by digital imaging fluorescence microscopy. AB - Temporal and spatial changes of lipid peroxides in a cultured colon cancer cell line, Colo-205 cells, were investigated after culturing with Kupffer cells by using 2',7'-dichlorofluorescein diacetate and a digital imaging processor equipped with an inverted microscope. By this method, we successfully visualized the alteration of lipid peroxides in the individual cancer cell. Without any prior activation, Kupffer cells isolated from an intact rat liver caused rapid increase in the intensity of dichlorofluorescein in tumor cells in a time dependent manner. The increase of the fluorescent intensity was significantly attenuated by pretreatment with superoxide dismutase. In ex vivo study using isolated perfused rat liver, dichlorofluorescein-preloaded cancer cells, which were transportally injected, were found to adhere to hepatic sinusoids and then to enhance their fluorescence. The present study suggested that the resident Kupffer cell-derived oxidative stress participates in the cytotoxic process against cancer cells by inducing intracellular lipid peroxidation. It may be sustained that Kupffer cells play a role in the host defence mechanisms against the liver metastasis of colon cancer cells. PMID- 1913615 TI - Butylated hydroxytoluene lacks the activity of phenobarbital in enhancing diethylnitrosamine-induced mouse liver carcinogenesis. AB - The effect of the food additive butylated hydroxytoluene (BHT) as an enhancer of liver carcinogenesis in mice was investigated. Liver carcinogenesis was initiated by intraperitoneal injection of diethylnitrosamine (DEN) in male B6C3F1 mice at 100 or 200 mumol/kg body weight once a week for 10 weeks (total exposure 1000 or 2000 mumol/kg body weight). After an exposure-free recovery interval of 4 weeks, groups of mice were fed either basal diet or diets containing either 5000 ppm BHT or 500 ppm phenobarbital (PB), as a positive control, for 24 weeks. Exposure to the initiating doses of DEN alone induced no liver foci at 10 weeks or at 14 weeks after the recovery period, but at termination at 38 weeks, foci and adenomas were present in a dose-related incidence. In the groups given BHT after DEN/recovery, the incidence and the multiplicity of liver foci and adenomas were not different from those in mice given only DEN/recovery, whereas, in the groups given PB after DEN, liver lesions were increased by 1.7-3.0-fold. In conclusion, BHT had no promoting or syncarcinogenic effect on DEN-induced mouse liver carcinogenesis, whereas under the same conditions, PB acted as an enhancer. PMID- 1913617 TI - Correlation between bromodeoxyuridine labelling and ornithine decarboxylase levels in normal rectal mucosa of patients with colorectal adenoma. AB - We studied rectal cell proliferation by means of bromodeoxyuridine labelling and ornithine decarboxylase activity assay in 16 patients with colorectal adenoma. In each patient, three rectal biopsy specimens taken from normal-appearing mucosa were incubated with bromodeoxyuridine (BrdU), fixed in ethanol and stained with avidin-biotin peroxidase complex using a monoclonal antibody against BrdU. In addition, two biopsies were homogenized and incubated with [1-14C]-ornithine for ornithine decarboxylase (ODC) assay. A direct, significant correlation was found between BrdU-labelling index and ODC levels in the mucosa (r = 0.6511, P less than 0.01). We conclude that BrdU labelling and ODC activity assay give comparable results in the analysis of cell proliferation rate of rectal mucosa. These methods are useful to investigate rectal cell proliferation pattern of patients with increased risk of colorectal cancer. PMID- 1913618 TI - Effects of dietary fat on hepatic microsomal metabolism of 1,2-dimethylhydrazine. AB - The present study was designed to examine the effects of different high fat diets on the liver microsomal metabolism of aminopyrine (AMP) and 1,2-dimethylhydrazine (DMH). Male Sprague-Dawley rats were fed either a low fat (5% corn oil) or high fat (20%) diets containing either corn oil, menhaden oil or beef tallow for a period of up to 9 months. Liver microsomes were assayed for N-demethylase activity for both AMP and DMH substrates at 2 weeks, 1, 6 and 9 months of diet only, and also after 1, 2, 5 and 10 DMH treatments (20 mg/kg body weight). The menhaden oil-fed group had consistently higher AMP demethylase activity, which increased up to 6 months and then declined. Beef tallow-fed rats had the highest DMH demethylase activity following DMH, but this decreased by 10 treatments. These data indicate that type and amount of dietary fat affects microsomal metabolism of carcinogens, which may enhance tumor initiation. PMID- 1913619 TI - Low incidence of Ha-ras oncogene mutations in human epidermal tumors. AB - Activation of the Ha-ras oncogene by point mutations has been suggested to play a role in animal skin carcinogenesis models. In this study, we investigated the significance of the Ha-ras mutations in human epidermal tumors. DNAs from paraffin-embedded tissues of benign and malignant human epidermal tumors (27 samples from 25 patients) were prepared and examined for point mutations of codons 12, 13 and 61 of Ha-ras gene by polymerase chain reaction and oligonucleotide hybridization. Only one sample of basal cell carcinoma and one sample of keratoacanthoma were found to carry an A to T transversion at the second position of codon 61. This low incidence of Ha-ras mutations suggests that the mutational activation of the gene may not be primarily involved in human epidermal tumorigenesis. PMID- 1913620 TI - Ornithine decarboxylase induction in mouse kidney as indicator of renal damage. Differential nephrotoxic effect of anticancer antifolate drugs. AB - High doses of folate and its quinazoline analogue with antitumour activity, N10 propargyl-5,8-dideazafolic acid (CB 3717), caused severe renal damage in mice, leading in the case of folate to death. The mouse kidneys increased in weight, which was accompanied by time- and dose-dependent induction of ornithine decarboxylase (ODC) activity. In contrast, methotrexate (MTX) had negligible effect on mouse kidneys except when applied together with the non-steroidal antiinflammatory drug, indomethacin. PMID- 1913621 TI - Relationship of the uptake and beta-oxidation of 18-carbon fatty acids with stimulation of murine mammary tumor cell growth. AB - The effects of stearic (18:0), oleic (18:1) and linoleic (18:2) acid on the in vitro growth of murine mammary tumor cell line 4526 were compared to 4526 uptake and beta-oxidation of those fatty acids. Both 18:1 and 18:2 stimulated, while 18:0 inhibited growth. Likewise, uptake and oxidation rates were much lower for 18:0 than for 18:1 and 18:2. The influence of glucose, insulin and fatty acid depletion on 4526 fatty acid incorporation and oxidation was also determined. The correlation between effects on in vitro growth and ability to assimilate 18:0, 18:1 and 18:2 may partially explain the stimulation by unsaturated and inhibition by saturated fatty acids of in vivo 4526 tumorigenesis. PMID- 1913622 TI - Multiple cancers of the upper aero-digestive tract: the challenge of risk factor identification. AB - Carcinomas of the upper aero-digestive tract (UADT) are among the most common neoplasms, particularly in developing countries. The generally poor prognosis for UADT cancer patients is further complicated by the occurrence during follow-up of additional cancers of the same or related sites. Proper quantification of the incidence of these second cancers and characterization of their risk factors have been plagued with methodological difficulties. The effects of tobacco and alcohol consumption vary with anatomic site, which requires that matching or adjustment by site be performed in any comparisons between single primary and multiple primary patients. Clinical variables, such as disease extension, treatment and survival, also influence risk of second malignancies. However, these parameters are also strongly interrelated, which makes it difficult to characterize their individual associations with risk or to control for their confounding effects when examining other variables. These shortcomings should be taken into consideration in the design of studies searching for genetic and other inter individual variations in susceptibility to multiple UADT malignancies. PMID- 1913623 TI - Effects of synthetic and naturally occurring flavonoids on benzo[a]pyrene metabolism by hepatic microsomes prepared from rats treated with cytochrome P-450 inducers. AB - Activity-directed fractionation of Trifolium pratense resulted in isolation of the isoflavone biochanin A, a potent inhibitor of metabolic activation of the carcinogen benzo[a]pyrene (B[a]P) in cells in culture. To determine the structural features required for maximal inhibition of cytochrome P-450 mediated metabolism of B[a]P, the inhibitory potencies of 23 flavonoids on metabolism of B[a]P to water-soluble derivatives were examined in liver S-9 homogenate from rats induced with Aroclor 1254. Flavones were much more efficient inhibitors than their corresponding isoflavone or flavanone analogs. Most flavonols were as effective inhibitors as their flavone analogs with the exception of kaempferide. Flavones with two hydroxyl or two methoxyl groups at positions 5 and 7 were the most active. Although all eight flavonoids tested effectively inhibited B[a]P metabolism by beta-naphthoflavone-induced microsomes, none were very effective inhibitors of B[a]P metabolism by phenobarbitol-induced microsomes, and only three were effective inhibitors of B[a]P metabolism by microsomes from non induced rats. These results indicate that flavones or flavonols that contain free 5- and 7-hydroxyls are potent inhibitors of P-450 induced by beta-naphthoflavone (P-450IA1 and/or P-450IA2) and may potentially be useful as chemopreventive agents against hydrocarbon-induced carcinogenesis. PMID- 1913624 TI - Effects of N-acyl dehydroalanines on phorbol ester-elicited tumor development and other events in mouse skin. AB - The free radical scavengers N-acyl dehydroalanines (AD compounds) were examined for their effect on several 12-O-tetradecanoylphorbol-13-acetate (TPA) elicited events in mouse skin. The induction of oxidant production by TPA in isolated mouse epidermal cells was reduced by approximately 70% by 1 mM paramethoxyphenyl acetyl dehydroalanine (AD5) and 80% by 1 mM parasulfoxyphenyl-acetyl dehydroalanine (AD19). These AD compounds also completely suppressed the TPA dependent stimulation of prostaglandin E2 synthesis in primary cultures of epidermal cells. Single and multiple topical applications on the dorsal skin of SENCAR mice of either AD5 or AD 19 inhibited TPA-induced epidermal hyperplasia but failed to inhibit epidermal ornithine decarboxylase induction. When used with TPA on initiated mice, AD19 did not inhibit papilloma formation; however, after 40 weeks of promotion, the carcinoma incidence was reduced by 50% in the AD19 group. These results suggest that reactive oxygens may be more important to the conversion of benign to malignant tumors than in the initial development of the benign tumors. PMID- 1913625 TI - Lipoxygenase: a new pathway for 2-aminofluorene bioactivation. AB - Soybean lipoxygenase mediated co-oxidation of 2-aminofluorene (2-AF), a putative carcinogen and teratogen, was examined. 2-AF metabolism was followed spectrally as a decrease in absorbance at 286 nm. The enzymatic oxidation displayed a pH optimum at 9.5 with a Km of 0.27 mM and specific activity of 521.7 +/- 46.6 nmol/min per nmol of enzyme. The generation of electrophilic 2-AF intermediate(s) capable of covalent binding to macromolecules was also investigated radiometrically. Significant binding to protein and calf thymus DNA was observed, suggesting clearly bioactivation of 2-AF. Several classical lipoxygenase inhibitors caused a marked inhibition of 2-AF oxidation as well as covalent binding to protein and DNA. These results strongly suggest that lipoxygenase is capable of 2-AF metabolism and this may represent another pathway for bioactivation of arylamines. PMID- 1913626 TI - Survival period of tumor-bearing mice is prolonged after the interferon-gamma producing gene transfer. AB - A highly tumorigenic keratinocyte-derived carcinoma cell line, designated as Pam T, was established from a Pam212 line. The intradermal injection of more than 10(5) of these cells into syngeneic BALB/c mice induced substantial tumors. The tumors progressively enlarged and then invaded the peritoneal cavity leading to the death of the host mice. To comprehensively investigate the effects of interferon-gamma on tumorigenicity, we manufactured interferon-gamma-producing PamT cells by interferon-gamma gene transfer and examined the characteristics of the tumors induced by these cells in syngeneic mice. Interferon-gamma producing cells exhibited an apparently similar in vitro cell growth pattern and in vivo tumor formation to control cells, but the mean survival of the mice with the interferon-gamma-producing cells was significantly longer compared with control mice. PMID- 1913627 TI - Differential expression of glycoproteins containing alpha-D-galactosyl groups on normal human breast epithelial cells and MCF-7 human breast carcinoma cells. AB - Cell surface glycoproteins were isolated from the lysates of 125I-labeled normal human mammary epithelial cells (NHMEC) and from the human breast carcinoma cell line MCF-7, of blood-group O phenotype, by affinity chromatography on Griffonia simplicifolia I lectin-Sepharose. Specific elution of glycoproteins from the column with methyl alpha-D-galactoside suggests the presence of alpha-D galactosyl groups on these moieties. SDS-PAGE analysis of isolated glycoproteins revealed both quantitative and qualitative differences between glycoproteins from normal and malignant cells. Three major glycoproteins of Mr 180 kDa, 85 kDa and the 44 kDa were obtained from MCF-7 cells. The 180-kDa glycoprotein was absent in NHMEC and the 44-kDa glycoprotein was very weakly expressed in these cells. The only glycoprotein which was found in almost equal amount in the lysate from both normal and malignant cells was the 85-kDa glycoprotein. These results indicate differences between normal human mammary epithelial cells and one kind of malignant human mammary epithelial cells, in the expression of glycoproteins containing alpha-D-galactosyl groups, irrespective of blood-group phenotype; they also demonstrate that alpha-D-galactosyl group are expressed in a very restrictive manner on the surface of this tumor cell line. PMID- 1913628 TI - Modulatory influences of clove (Caryophyllus aromaticus, L) on hepatic detoxification systems and bone marrow genotoxicity in male Swiss albino mice. AB - Modulatory effects observed due to clove administration (0.5%, 1% and 2% w/w in the diet) to Swiss albino mice for 10, 20 and 30 days in the hepatic levels of cytochrome P-450 (Cyt. P-450), cytochrome b5 (Cyt. b5), aryl hydrocarbon hydroxylase (AHH), glutathione S-transferase (GST), DT-diaphorase (DTD), acid soluble sulfhydryl (SH) content and radiation-induced malondialdehyde (MDA) formation were recorded. Enhanced GST, Cyt. b5 and SH levels were observed in all the treatment groups, excepting those maintained on a 0.5% diet for 10 days which did not show significant increase in the GST and SH levels as compared to their respective controls. Significant reduction in Cyt. P-450 and MDA levels was observed in all groups at 30 days duration. While AHH levels remained unaltered by clove administration, DTD activity was elevated by 1% and 2% clove diets at 30 days duration. An in vivo bone marrow micronucleus assay demonstrated that administration of 0.5% and 2% clove diets for 10 days neither significantly induced micronuclei nor could effectively modulate the 7, 12 dimethylbenz[a]anthracene genotoxicity in mice. The results suggest whole cloves as potential chemopreventive agents. PMID- 1913630 TI - Cancer associated antigen CA19-9 in colonic effluent of patients with neoplasia of the colon and inflammatory bowel disease. AB - We measured colonic effluent samples from 10 patients with colorectal cancer, 13 with adenomatous polyps, 14 with normal colons and compared them to 10 patients with inflammatory bowel disease by measuring this CA19-9 content. Results showed considerable overlap between the different pathologic categories, making differentiation impossible. A lower level of CA19-9 in the effluent samples from patients with adenomas was noted. These differences were reproducible for assays performed several months apart. CA19-9 may originate from the upper gastrointestinal tract since large amounts are present in pancreatico-biliary secretions. This antigen is therefore not useful in the diagnosis of neoplasia or inflammatory bowel disease using colonic effluent samples as the test material. PMID- 1913629 TI - Regulation of cellular trans-activating activities in two different promonocytic leukemia cell lines. AB - Trans-activating activities of certain cellular promoter/enhancer genes may reflect the underlying mechanism for cellular differentiation. We have used two promonocytic leukemia cell lines, U937 and HL-CZ, which differ in their differentiation antigen expression. While both cell lines express CD15 antigen, only the former expresses both CD4 and CD10 antigens. These phenotypes suggest that these two cell lines appear to be arrested at different stages of differentiation. Some regions of the long terminal repeat (LTR) of human immunodeficiency virus-1 (HIV-1) contain nucleotide sequences which bind cellular trans-activating factors such as NF-kappa B and Sp1. These sequences are also present in cellular regulatory gene sequences. The cell lines have been transfected by electroporation with a nested series of deletion mutants containing different lengths of the promoter/enhancer region for HIV-LTR. The promoter/enhancer region has been linked to a 'reporter' chloramphenicol acetyl transferase (CAT) gene. We have found that promoter/enhancer trans-activation is markedly enhanced by treating transfected cells with 12-O-tetradecanoylphorbol-13 acetate (TPA), while similar treatment with tumor necrosis factor-alpha (TNF alpha) slightly enhanced activation. U937 cells always showed much greater transactivating activities than did HL-CZ cells. Deletion of a negative regulatory element (NRE) from the LTR resulted in an enhanced transactivation, while deletions affecting NF-kappa B and/or Sp1 binding sites markedly reduced transactivation. Deletion of both NRE and NRF, a second negative regulatory factor binding site, from the LTR restored the transactivation. However, in the presence of TPA, deletion of NRE sequence without concomitant deletion of the downstream NRF binding sequence was sufficient for recovering transactivation. Since these two cell lines have shown subtle differences in these responses, it may be speculated that monocytes at different stages of differentiation may respond in different ways, qualitatively and/or quantitatively, to signal transduction factors involved in the transactivation of cellular genes. PMID- 1913631 TI - The septic syndrome. An oncologic treatment challenge. AB - The septic syndrome has three phases, characterized by alterations in tissue perfusion (phase I), fluid volume (phase II), and cardiac output (phase III). It must be viewed as a continuum: the degree of illness and the rate of mortality increase with each stage. Each phase must be clearly understood by health-care professionals for them to be able to intervene actively to prevent a patient's progressive deterioration. Since the septic syndrome frequently cannot be treated effectively in the advanced stage, the nurse's role must focus on early detection of infection, thorough evaluation of all the parameters, and expeditious initiation of treatment in collaboration with the physician. The high mortality of cancer patients who develop septic shock is an incentive for nurse and physician to work together to prevent this serious condition and provide maximum support if it should occur. The nurse's ability to make critical judgments derived from a knowledgeable assessment of clinical data can positively influence the outcome. The timeliness of the nursing intervention may determine the patient's fate. PMID- 1913632 TI - Fatigue affecting family caregivers of cancer patients. AB - Fatigue, a universally reported symptom, may be one of the most prevalent feelings of people suffering physical or mental diseases. An understanding of the factors leading to fatigue in the caregiving population can contribute to better care and support of both the cancer patient and caregiver. The purpose of this article is to investigate and describe the experience of fatigue among caregivers of cancer patients, in relation to caregiver age, employment status, number of hours of care provided daily, duration of caregiving, and the impact upon the caregiver's schedule. A sample of 248 caregivers of cancer patients, participating in the Family Homecare Cancer Study, were surveyed regarding fatigue related to their caregiving roles. No relationship was found between severity of fatigue experienced by the caregiver of the cancer patient and caregiver age, employment status, the number of hours of daily caregiving, or the duration of caregiving. However, a significant relationship was found between fatigue and the impact of care on the daily schedule. This finding has strong implications for the oncology nurse, because the more the caregiver's schedule is a burden, the greater will be the fatigue experienced. PMID- 1913633 TI - A critical appraisal of the research literature investigating fatigue in the individual with cancer. AB - Fatigue is a commonly experienced symptom, which may be a component of virtually any disease and can have a psychological, physical, or mixed origin. Nurses need to understand the onset, duration, and progression of fatigue to intervene successfully with the cancer patient adapting to diagnosis and treatment. While the literature is an important source of information, results of research studies must be critically interpreted before proceeding with practice guidelines based on research findings. A critical appraisal of the research literature investigating the problem of fatigue in individuals with cancer was conducted. There is strong evidence to suggest that fatigue is a prevalent problem among cancer patients receiving chemotherapy and radiation therapy. However past research has been limited by methodological problems. Typically, studies fail to include a control group, do not control for possible confounding variables, and have restricted measurement to unidimensional scales with limited reliability and validity. While several correlates of fatigue have been postulated, research to date has found no consistent relationships among such correlates as weight loss, anemia, or psychological distress. This article reviews what is currently known about fatigue in the cancer patient and how future research could be designed to improve on past measurement and sampling problems. PMID- 1913635 TI - The influence of the AIDS epidemic on the master's-prepared oncology nurse. AB - More than 139,000 cases of the acquired immunodeficiency syndrome (AIDS) have been reported to the Centers for Disease Control. Many of these individuals will develop malignancies, such as Kaposi's sarcoma and malignant lymphoma. Because of the neoplastic complications of AIDS and the terminal nature of this disease, some centers employ oncology clinical nurse specialists to coordinate the care of patients. This study was designed to determine the extent to which master's prepared oncology nurses care for patients with AIDS in the United States, the type of care these nurses provide, their sources of AIDS-related information, and the risks they perceive in caring for patients with AIDS. This information will guide educators to develop graduate curricula and continuing education programs that include useful information on the care of patients with AIDS. These results will also direct administrators to consider extra stressors imposed on the master's-prepared oncology nurse who also cares for those with AIDS. PMID- 1913634 TI - Support patterns for spouse-caregivers of cancer patients. The effect of the presence of minor children. AB - This study examines the support received by spouse-caregivers of cancer patients with minor children. The pattern of help encountered by these caregivers is compared to that of other caregivers, either living alone with the cancer patient or together with their adult children. This comparison leads to an exploration of compensatory support patterns depending on the source of help and the living arrangements. The study is based on a convenience sample of 232 spouse-caregivers of cancer patients in the Midwest. The findings suggest that other family members are willing to provide additional support when minor children are present in the household of the caregiver-patient dyad. However, this compensatory pattern does not extend to the situation of caregiver and patient living alone, nor do friends and neighbors engage in compensatory support behavior. PMID- 1913637 TI - Pain management of cancer in Ghana. PMID- 1913636 TI - Measuring breast self-examination proficiency. A scoring system developed from a paired comparison study. AB - A continuous scoring strategy yielding a proficiency score on breast self examination (BSE) performance was developed and validated. The method of paired comparisons was used to provide a rank ordering on an interval scale of the eight components of the evaluation tool. Twenty-one experts in teaching the MammaCare method of breast self-examination participated in the survey to help in developing the composite measure of proficiency in BSE performance. Data on each component of BSE were collected quantitatively, and performance scores were computed using a formula incorporating the weighting schema derived from the paired comparisons procedure. A comparison of preteaching versus postteaching mean performance scores on BSE indicated that the scoring system worked even when the teaching method varied. The scoring system presented here is a start on the development of a tool that can be useful to researchers using relative performance as a measure in BSE studies. The components of the scoring system can be used by nurses in the practice setting as a checklist for evaluating BSE performance. PMID- 1913638 TI - Estimation of the dividing fraction and potential doubling time of tumors using cytochalasin B. AB - We devised a new in vitro method to estimate the proportion of dividing cells and the potential doubling time (Tpot) of tumors using the same technique as with the cytokinesis-block micronucleus assay. The usefulness of this methodology was confirmed by comparing the data with those obtained by flow cytometry after bromodeoxyuridine (BrdUrd) incorporation. Xenografted human and murine tumors were excised 0.5-8 h after BrdUrd injection and disaggregated to single cells. A portion of these cells was then plated in dishes to which 1 or 2 micrograms/ml cytochalasin B were added. These concentrations of cytochalasin B blocked cytokinesis but not karyokinesis with the result that cells became multinucleate after mitoses. At every 12 or 24 h of culture, the proportion of multinucleate cells and the total number of nuclei and cells were scored. The remaining cells were analyzed with a flow cytometer and the BrdUrd-labeling index and Tpot were determined. In all 8 tumor lines studied, the proportion of multinucleate cells reached a plateau within 3-7 days of culture, and we therefore defined the dividing fraction as the plateau value. The dividing fraction ranged between 33 and 98% and clearly tended to be high in rapidly growing tumors. A significant correlation was seen between the dividing fraction and BrdUrd-labeling index (r = 0.74, P less than 0.001). The increase in the average number of nuclei per cell also tended to be higher in rapidly growing tumors. The Tpot was estimated as the time for this nucleus/cell ratio to reach 2.0. In 7 of 8 tumor lines, Tpot values estimated by this method compared reasonably with those estimated by the BrdUrd method. Therefore, this simple technique, originally developed for radiosensitivity prediction, would also seem to be useful in estimating tumor proliferative activity. PMID- 1913639 TI - Hypoxic fractions in xenografted human colon tumors. AB - We investigated the percentage of radiobiologically hypoxic cells within 11 different xenografted human colon tumors using an in vivo-in vitro excision assay technique. Tumors were excised at average volumes of 750 mm3, and it was found that hypoxic fractions varied from less than 1% (clone D) to over 80% (HCT-8). The geometric mean hypoxic percentage was 10.4% (95% confidence interval, 4.9 to 22.1%). Comparison of the percentage of hypoxia results from the xenografted human colon tumors to published data from xenografted melanomas suggests that transplanted colorectal tumors as a class contain significantly less hypoxia than do the melanomas. PMID- 1913640 TI - Pharmacokinetics of intravesical mitomycin C in superficial bladder cancer patients. AB - Intravesical mitomycin C (MMC) therapy is used to treat superficial bladder cancer. This study was to establish the intra- and intersubject variabilities in the systemic (plasma) and target site (bladder) exposure to the drug and to identify the factors which contribute to these variabilities. The pharmacokinetics of MMC were studied in 10 patients. Treatment consisted of transurethral tumor resection followed by six weekly intravesical treatments with MMC (20 mg in 40 ml of water). The dosing solution was maintained in the bladder for 2 h. Pharmacokinetic studies were performed at the time of the first, fourth, and sixth or first, second, and fourth treatments with MMC for a total of 28 treatments. Concentration-time profiles of the plasma and bladder contents (i.e., urine), urine volumes, and urine pH were determined during and for up to 4 h after intravesical administration. Maximal plasma MMC concentrations averaged 43 ng/ml (range, 2.1-180.5 ng/ml) in treatment 1. In comparison, the MMC plasma concentration for myelosuppression reported in the literature is 400 ng/ml. Maximal plasma concentrations in treatments 2, 4, and 6 were at least 4-fold lower than those in treatment 1 and in most cases were below the detection limit of 0.5 ng/ml. This indicates that the absorption of MMC during the later treatments was less than in the first treatment given shortly after surgery. Urinary MMC concentrations during instillation declined from 519.4 +/- 34.8 micrograms/ml (mean +/- SD) in the dosing solution to 64.6 +/- 39.4 micrograms/ml 2 h after instillation. Thus, the superficial bladder tissue was exposed to drug concentrations 300- to greater than 34,000-fold higher than the plasma-perfused systemic tissues. Intravesical exposure to MMC, as determined by the area under the urine concentration-time curve, showed large intra- and intersubject variabilities (range, 2,185-40,411 micrograms-min/ml). Pharmacokinetic analysis showed that the bladder exposure to MMC inversely correlated with the residual urine volume at the time of drug administration (P less than 0.001), the urine production rate (P = 0.05), and the rate of drug removal by degradation and absorption during therapy (P less than 0.01). At the end of the 2-h treatment, recovery of MMC from the bladder instillate ranged from 1 to 100% and correlated with the urine pH at the time of removal (P less than 0.001). At pH between 5 and 5.5, less than 30% of the dose was recovered.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1913641 TI - Increase in immunogenicity and sensitivity to natural cell-mediated cytotoxicity following in vitro exposure of MCA105 tumor cells to ultraviolet radiation. AB - The effect of short wave length ultraviolet C (UVC) light irradiation on tumor cell immunogenicity and sensitivity to natural cell-mediated cytotoxicity was studied. Two consecutive courses of UVC irradiation of 3LL Lewis lung carcinoma and MCA105 fibrosarcoma increased their immunogenicity and sensitivity to lysis by normal spleen cells. Analysis of the effector cells involved in lysis of the parental MCA105 and UV-treated MCA105UV tumor cells was performed by comparing the cytotoxic activity of normal spleen cells containing both natural killer (NK) and natural cytotoxicity (NC) cell activity (NK+, NC+) with: (a) normal spleen cells in which NC activity was neutralized by anti-tumor necrosis factor (TNF) antibodies (NK+, NC-); (b) NK-depleted or NK-deficient spleen cells (NK-, NC+); and (c) NK-depleted or -deficient spleen cells with NC activity blocked by anti TNF antibodies (NK-, NC-). In addition, the ability of polyinosinic-polycytidylic acid or interleukin 2-stimulated spleen cells to lyse UV-treated and untreated tumor cells in the presence or absence of anti-TNF antibodies was also investigated. Lysis of MCA105 cells was shown to be mediated mostly by NC cells, since it was inhibited in the presence of anti-TNF antibodies and was not significantly affected by depletion or stimulation of NK cells. UV irradiation of MCA105 tumor cells substantially increased their sensitivity to both NK and NC effector cells. Augmentation of NK sensitivity of MCA105UV cells was associated with an increase in their lysability by large granular lymphocyte-derived cytolytic granules. UVC treatment of tumor cells also increased their sensitivity to lysis by recombinant TNF-alpha, pointing to the possible mechanism responsible for the increase in their sensitivity to NC cell-mediated cytotoxicity. Indeed, selection of MCA105UV cells for resistance to TNF led to resistance to spleen cell-mediated NC cytotoxicity. UVC irradiation did not affect internalization and degradation of TNF by MCA105UV cells but substantially increased sensitivity to TNF-induced DNA fragmentation. The results of this study indicate that UV irradiation can be a potent and stable modulator of the immunobiological properties of tumor cells. PMID- 1913642 TI - Characteristics of the biphasic action of androgens and of the potent antiproliferative effects of the new pure antiestrogen EM-139 on cell cycle kinetic parameters in LNCaP human prostatic cancer cells. AB - The most potent steroid in human prostatic carcinoma LNCaP cells, i.e., dihydrotestosterone (DHT), has a biphasic stimulatory effect on cell proliferation. At the maximal stimulatory concentration of 0.1 nM DHT, analysis of cell kinetic parameters shows a decrease of the G0-G1 fraction with a corresponding increase of the S and G2 + M fractions. In contrast, concentrations of 1 nM DHT or higher induce a return of cell proliferation to control levels, reflected by an increase in the G0-G1 fraction at the expense of the S and especially the G2 + M fractions. Continuous labeling for 144 h with the nucleotide analogue 5'-bromodeoxyuridine shows that the percentage of cycling LNCaP cells rises more than 90% after treatment with stimulatory concentrations of DHT, whereas in control cells as well as in cells treated with high concentrations of the androgen, this value remains below 50%. Although LNCaP cells do not contain detectable estrogen receptors, the new pure steroidal antiestrogen EM-139 not only reversed the stimulation of cell proliferation and cell kinetics induced by stimulatory doses of DHT but also inhibited basal cell proliferation. PMID- 1913643 TI - DNA adducts of the antitumor agent diaziquone. AB - We have studied adduct formation of the antineoplastic agent diaziquone (AZQ; NSC 182986) with DNA and nucleotides in vitro. The aziridine moieties of AZQ can be expected to interact covalently with DNA which, in turn, presumably elicits the antitumor activity. We analyzed AZQ-DNA adducts by a modified 32P-postlabeling assay involving purification of the nuclease P1-enriched labeled adducts by high salt C18 reversed-phase thin-layer chromatography and separation of the eluted adducts on a polyethyleneimine-cellulose layer using non-urea salt solutions. Modification of calf thymus DNA with AZQ produced two major (22% and 40%) and at least eight minor adducts. At equal concentrations of AZQ and DNA (1 micrograms/microliters each), peak binding was observed in about 2 h [1926 +/- 378 (SD) fmol/micrograms of DNA] with the binding levels remaining practically unchanged through 4 h. However, incubation for 24 h resulted in over 40% decline, indicating adduct instability. AZQ was found to be highly reactive in vitro as evidenced by its substantial binding (49 +/- 14 fmol/micrograms of DNA) even at a DNA:AZQ ratio of 100:1. When incubated with mononucleotides, AZQ reacted extensively with adenine, guanine, and cytosine but only slightly with thymine. Cochromatography of the modified DNA and nucleotides revealed that one of the major adducts and several minor adducts were guanine derived. The aziridine rings of AZQ were found to be the main reactive sites as its monoaminoalcohol derivative showed as much DNA reactivity as did the parent compound, but no activity was observed when both aziridine groups were hydrolyzed to diaminoalcohols. The improved 32P-postlabeling assay seems capable of detecting relatively polar adducts such as those formed with AZQ at a level of one adduct/10(9) nucleotides. PMID- 1913644 TI - Effects of H-2Kb gene on expression of melanoma-associated antigen and lectin binding sites on BL6 melanoma cells. AB - An H-2Kb negative BL6 melanoma clone (BL6-8) was transfected with plasmids containing either the class I H-2Kb or class II H-2IAk gene in combination with the neor gene. The effects of the transfected genes on the expression of the melanoma-associated antigen (MAA) recognized by the monoclonal antibodies MM2-9B6 and MM2-3C6 and the cell surface carbohydrates recognized by 15 different lectins were studied. The original H-2Kb- clone or clones transfected with neor or class II H-2IAk genes expressed high levels of MAA and very low levels of soybean agglutinin (SBA), Griffonia simplicifolia I-B4 (GSIB4), and peanut agglutinin (PNA) lectin-binding sites. In contrast, clones that expressed high levels of the transfected H-2Kb gene completely lost the expression of MAA. In addition, these clones were characterized by the appearance of high levels of expression of the sugars specifically reacting with SBA, GSIB4, and PNA lectins. When the original BL6-8 clone was transfected with the H-2Kd gene, 25 clones subsequently isolated had relatively low expression of the transfected H-2Kd gene but high expression of the endogenous H-2Kb gene accompanied by an alteration in expression of the MAA and lectin binding identical with patterns common for H-2Kb+ melanoma cells. These changes were not due to the transfection, plasmid construction, or place of insertion, since similar phenotypic characteristics were found in H-2Kb+ but not H-2Kb- clones isolated from the N-methyl-N'-nitro-N-nitrosoguanidine-treated BL6T2 or parental BL6 melanoma lines. In total, 73 BL6 melanoma clones were investigated and all of the 41 H-2Kb+ clones displayed loss of MAA and appearance of SBA, GSIB4, and PNA-binding sugars. None of the 32 H-2Kb- clones showed these changes. This study indicates that the class I H-2Kb gene product might alter several phenotypic properties of BL6 melanoma cells. The mechanisms of these changes remain unknown. We consider that these effects of the class I H-2Kb gene are indirect, involving interactions with the B-tropic ecotropic retrovirus specific for melanomas of C57BL/6 mice origin. PMID- 1913645 TI - Measurement of 4-aminobiphenyl-hemoglobin adducts in lung cancer cases and controls. AB - Hemoglobin adducts of the activated carcinogenic aromatic amine 4-aminobiphenyl have been measured in a case-control study of lung cancer. Data obtained for lung cancer cases are compared to those obtained for controls that consisted of patients with either chronic obstructive pulmonary disease or non-pulmonary cancers. Both simple and multivariate analysis found a positive association of 4 aminobiphenyl-hemoglobin adducts with the quantity of tobacco smoked as determined by either urine cotinine or questionnaire data. No association was found between 4-aminobiphenyl-hemoglobin adducts and cancer diagnosis, and adduct levels were not related to remote tobacco use, i.e., total pack years of smoking. There was no association between the levels of adducts detected and the ability of an individual to metabolize debrisoquine (debrisoquine metabolic phenotype, CYP2D6). Whereas 4-aminobiphenyl-hemoglobin adduct levels reflected recent tobacco smoking, they were not correlated with lung cancer risk. PMID- 1913646 TI - Biochemical evidence that glucocorticoid-sensitive cell lines derived from the human leukemic cell line CCRF-CEM express a normal and a mutant glucocorticoid receptor gene. AB - To characterize the immunoreactive glucocorticoid receptor (GR) protein present in "receptorless" (r-) mutants isolated from the glucocorticoid-sensitive (dexs) human leukemic cell line CEM-C7, binding of [3H]dexamethasone was determined in extracts prepared from the sensitive cell line 6TG1.1 and the r- mutant ICR27TK.3 after gentle freeze-thaw lysis and low-speed centrifugation. Under these conditions there was significant high-affinity binding activity in r- extracts assayed at 4 degrees C but not at 23 degrees C. Loss of binding at 23 degrees C was not a function of GR proteolysis or denaturation of the steroid-binding site and could be prevented by the addition of sodium molybdate. Dissociation of ligand from either activated or unactivated receptors in r- extracts was significantly more rapid than from receptors in extracts prepared from normal cells, suggesting that the defect in receptors in r- cells is the result of mutation in the ligand-binding site. While the rate of dissociation from unactivated receptors in r- extracts was linear, dissociation from receptors in extracts of 6TG1.1 cells was biphasic. Analysis of these dissociation curves, as well as dissociation from receptors in the B-cell line IM-9, indicated that the mutant gene present in r- cells is also present in the dexs parental cell line. This conclusion is consistent with our previous hypothesis (J.M. Harmon et al., Mol. Endocrinol., 3:734-743, 1989) that glucocorticoid-sensitive CCRF-CEM cells express both a normal (GR+) and a mutant (GR*) allele. PMID- 1913647 TI - Increased survival after treatments with anticancer agents of Chinese hamster cells expressing the human Mr 27,000 heat shock protein. AB - A family of 10 thermoresistant cell lines cloned from Chinese hamster cells transfected with a plasmid containing the structural gene for the small human Mr 27,000 heat shock protein (HSP27) was used to assess the putative role of this heat shock protein in chemoresistance. These cells express varying amounts of human HSP27 in addition to the normal level of endogenous hamster HSP27. As previously observed in the case of thermoresistance, a significant positive linear correlation (P less than 0.05) was found between cell survival in response to doxorubicin and the total amount of HSP27 expressed. Some clones were also examined for resistance to other drugs and chemicals. A statistically significant increased survival relative to the parental cells was observed following treatment with daunorubicin (three clones studied), colchicine, vincristine, actinomycin D, hydrogen peroxide, and sodium arsenite (one clone studied). However, the clone which expressed the highest level of HSP27 was as sensitive as control cells to the cytotoxic action of bis-chloronitrosourea and 5 fluorouracil. The relationship between HSP27 overexpression and increased resistance to cytotoxic agents was also evaluated in three independent pooled cell populations stably transformed with both the human HSP27 and the xanthine guanine phosphoribosyltransferase gene and selected on the basis of resistance to mycophenolic acid and aminopterin. The results indicated that these cells survived significantly better than the control cells transfected with the marker gene only when exposed to doxorubicin. HSP27-mediated cellular protection was not associated either with decreased drug accumulation or with overexpression of P glycoprotein. It is suggested that HSP27 might be involved in some form of chemoresistance and could participate in the development of clinical resistance to antineoplastic drugs. PMID- 1913648 TI - Human carcinoid cell production of paracrine growth factors that can stimulate fibroblast and endothelial cell growth. AB - A serotonin-secreting human pancreatic carcinoid cell line (BON) is demonstrated to express transcripts for all three mammalian types of transforming growth factor beta (TGF beta 1, 2, and 3). Similarly, freshly excised carcinoid tumors from six patients were also found to express mRNA for all three of the type-beta TGFs. Medium conditioned by BON cells had detectable TGF beta activity, although most of the activity was latent as determined by radioreceptor assay with and without prior acid treatment. However, nonactivated BON-conditioned medium stimulated DNA synthesis, soft agar growth, and an increase in TGF beta 1 and fibronectin mRNA expression in AKR-2B fibroblasts. In addition, BON-conditioned medium had a potent endothelial cell growth-stimulatory activity. Since the TGF beta s inhibit growth of endothelial cells, the presence of other growth factors was suspected. TGF alpha, c-sis, and basic fibroblast growth factor transcripts were also found to be expressed by the BON carcinoid cells. These data indicate that multiple peptide growth factors may have a paracrine role in the desmoplastic reaction accompanying carcinoid tumors. PMID- 1913649 TI - Individual susceptibility to induced chromosome damage and its implications for detecting genotoxic exposures in human populations. AB - In a previous study, we observed a bimodal distribution of sensitivity to sister chromatid exchange (SCE) induction by diepoxybutane (DEB) in lymphocytes from healthy individuals. Twenty-four % of the participants had increased sensitivity to in vitro induction of SCEs and chromosomal aberrations. These same participants also had significantly higher frequencies of uninduced or baseline SCE frequencies. In the present study, we measured baseline and DEB-induced SCE frequencies in 55 healthy female volunteers. Eleven of 55 [20%] women were relatively sensitive to DEB induction of SCEs. Baseline SCE frequencies in these sensitive individuals [10.4 +/- 0.7 (SD) SCEs/cell] were significantly higher [P less than 0.001; Student's t test] than baseline SCE frequencies in the remaining 44 individuals [8.0 +/- 0.9 SCEs/cell]. Similar increases in SCEs were observed when the analysis was restricted to the upper 10% of the SCE distribution (high frequency SCE analysis). The phenotype of DEB sensitivity accounted for 58% of the variation among individual SCE scores. Given the population frequency of this sensitivity to SCE induction and the high proportion of variance in SCEs for which it accounts, failure to account for this factor could seriously distort conclusions about SCE measures associated with other environmental exposures. The most likely result of such unexplained variability (type II error) would be bias toward the null hypothesis. Also, the likelihood that individual variations contribute to false positive results is expected to be greatest in studies that compare small numbers of exposed and nonexposed individuals. To summarize, these results confirm our earlier study and show that increased baseline SCE frequencies can be indicative of increased sensitivity to certain classes of mutagenic carcinogens. Identification of DEB-sensitive persons could be used to increase the sensitivity of SCE analysis in monitoring studies to detect exposure to genotoxins. PMID- 1913650 TI - Sequential analyses of the growth and morphological characteristics of aberrant crypt foci: putative preneoplastic lesions. AB - The main objective of the present study was to sequentially analyze growth and morphological characteristics of aberrant crypt foci (ACF) in the rat colon. Sprague-Dawley rats were given a single injection of a carcinogenic dose of 1,2 dimethylhydrazine-HCl and at varying time points ranging from 2 to 57 weeks, groups of 5 rats were terminated. The number and crypt multiplicity of ACF were determined in the distal 8 cm of the colon. In addition, ACF were processed for histology and then graded for the presence of nuclear atypia using a score of 0 4. The findings of the present study demonstrated that ACF exhibit the characteristics expected for precursor lesions. ACF were present at all time intervals in large numbers in the colons of rats treated with 1,2 dimethylhydrazine-HCl and were present when adenocarcinomas were observed. The number of ACF with 4 or more crypts and those exhibiting a higher grade (grade 4) of nuclear atypia increased significantly at or beyond 19 weeks. These features of ACF, particularly the presence of nuclear atypia indicative of dysplasia, provide strong support for the hypothesis that ACF are precursor lesions of chemically induced colon cancer. PMID- 1913652 TI - Overcoming the activity of mammary carcinoma suppressor gene in Copenhagen rats by v-H-ras oncogene transfer into mammary epithelial cells in situ. AB - Susceptibility to mammary cancer in rats is genetically controlled by both susceptibility and suppressor genes. The Copenhagen (COP) rat strain is highly resistant to both spontaneous and induced mammary carcinogenesis. The resistant trait is due to the inheritance of an autosomal dominant allele termed mammary carcinoma suppressor (mcs) gene. To test whether the activity of mcs gene can suppress the transforming potential of an activated oncogene, we introduced v-H ras oncogene into COP mammary epithelial cells in situ using a replication defective retroviral vector. v-H-ras transfer caused the rapid development of mammary carcinomas at high multiplicities. Hormonal promotion further increased the penetrance of the activated ras gene. Compared with the mammary carcinoma susceptible Wistar Furth (WF) rat strain, tumor development in the COP rat followed analogous kinetics. However, COP tumors were more differentiated and less locally invasive than were WF tumors. The possible role of the mcs gene in mammary differentiation is discussed. PMID- 1913651 TI - Activation of amino-alpha-carboline, 2-amino-1-methyl-6-phenylimidazo[4,5 b]pyridine and a copper phthalocyanine cellulose extract of cigarette smoke condensate by cytochrome P-450 enzymes in rat and human liver microsomes. AB - The ability of cigarette smoke condensate to induce a genotoxic response has been measured in liver microsomal and reconstituted monooxygenase systems containing rat and human cytochrome P-450 (P-450) enzymes, as determined by umu gene expression in Salmonella typhimurium TA1535/pSK1002. The reactivities of amino alpha-carboline and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), two compounds known to be present at considerable levels in cigarette smoke condensate, were also determined and compared with regard to genotoxicity. Amino alpha-carboline and PhIP are activated principally by P-450 1A2 enzymes in human and rat liver microsomes: (a) activation of both compounds was catalyzed efficiently by liver microsomes prepared from rats treated with 5,6-benzoflavone, isosafrole, or the commercial polychlorinated biphenyl mixture Aroclor 1254, and the activities could be considerably inhibited by antibodies raised against P-450 1A1 or 1A2; (b) the rates of activation of these compounds were correlated with the amount of human P-450 1A2 and of phenacetin O-deethylation activity in different human liver microsomal preparations, and these activities were inhibited by anti-P-450 1A2; (c) reconstituted enzyme systems containing P-450 1A enzymes isolated from rats and humans showed the highest rates of activation of amino-alpha-carboline and PhIP. In rat liver microsomes PhIP may also be activated by P-450 3A enzymes; activity was induced in rats treated with pregnenolone 16 alpha-carbonitrile and was inhibited by anti-human P-450 3A4. However, in humans the contribution of P-450 3A enzymes could be excluded as judged by the very low effects of anti-P-450 3A4 on the microsomal activities and poor correlation with P-450 3A4-catalyzed activities in various liver samples. Cigarette smoke condensate strongly inhibited the activation of several potent procarcinogens by human liver microsomes, particularly the reactions catalyzed by P-450 1A2, but was not so inhibitory of the activation reactions catalyzed by P 450 3A4 and of P-450 2D6-catalyzed bufuralol 1'-hydroxylation. Genotoxic components of the cigarette smoke condensate were extracted by using copper phthalocyanine cellulose (blue cotton). Genotoxicity of this extract was observed only after activation by P-450, and the inhibition of P-450 1A2 activities by these extracts was slight.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1913653 TI - Antiproliferative activity of a pregnancy recognition hormone, ovine trophoblast protein-1. AB - Ovine trophoblast protein-1 (oTP-1) is the alpha-interferon (IFN alpha) variant, secreted by conceptuses and referred to as type I trophoblast interferon, that is responsible for maternal recognition of pregnancy in sheep. We have previously shown that oTP-1 is as potent an antiviral agent as any known IFN. IFNs also possess anticellular activity and are, in fact, used in cancer therapy and have been found to be effective in the treatment of cancer such as myelogenous and hairy cell leukemias. A significant problem with the currently used IFNs is the undesirable side effect of toxicity at high concentrations. In this study, we examined the anticellular activity and toxicity of oTP-1. It inhibited proliferation but did not exhibit toxicity at high concentrations, unlike known IFN alpha S. In an anticellular assay using colony formation of both the human amnionic line, WISH, and the bovine epithelial line, MDBK, oTP-1 inhibited both colony size and number. oTP-1 was as effective as human and bovine IFN alpha s on human and bovine cells, respectively; thus, it displays potent cross-species activity. Its activity was dose dependent, and inhibition of proliferation could be observed at concentrations as low as 1 unit/ml. Concentrations as high as 50,000 units/ml stopped proliferation, while viability was not impaired. Cell cycle analysis revealed an increased proportion of cells in S phase and a corresponding decreased proportion of cells in G2/M after 48 h of oTP-1 treatment. Therefore, oTP-1 appears to inhibit progress of cells through S phase. oTP-1 antiproliferative effects can be observed as early as 12 h after after the initiation of culture and are maintained through 6 days. Thus, oTP-1 exhibits potent anticellular activity without toxicity across species and may have therapeutic potential as an antitumor agent without the toxic effects generally associated with IFNs. PMID- 1913654 TI - K-ras activation in premalignant and malignant epithelial lesions of the human uterus. AB - We previously reported (Cancer Res., 50:6139-6145, 1990) a significant frequency of activating point mutations in codon 12 of the K-ras oncogene in endometrial adenocarcinomas of the uterine corpus (series 1). To further define the role of ras activation in the development of endometrial adenocarcinoma, we surveyed cystic, adenomatous, and atypical hyperplasias of uterine endometrium and additional cases of endometrial and cervical carcinoma (series 2) for the presence of activating mutations in cellular protooncogenes of the ras family. Polymerase chain reaction was performed from deparaffinized sections of formalin fixed paraffin-embedded tissue. We screened for point mutations in codons 12, 13, and 61 of the K-, H-, and N-ras genes by dot blot hybridization analysis with mutation-specific oligomers. Mutations in K-ras were also confirmed by direct genomic DNA sequencing. Of 19 endometrial adenocarcinomas in series 2, point mutations in ras genes were found in 7 tumors. Six contained single-base substitutions, five in codon 12 of K-ras and one in codon 12 of N-ras. The seventh tumor contained two different point mutations in codon 12 of K-ras. In one endometrial adenocarcinoma, tumor cells with point mutations in K-ras were predominantly localized to a portion that had a more aggressive histological pattern. In endometrial hyperplasia, K-ras mutations, one in codon 12 and one in codon 13, were found in 2 of 16 hyperplasias histologically classified as atypical and clinically considered premalignant. None of 6 adenomatous hyperplasias and none of 12 cystic hyperplasias, the latter of which is considered clinically benign, contained any detectable ras mutations. No mutations in H-ras were detected in either carcinomas or hyperplastic tissue. PMID- 1913655 TI - Prognostic significance of argyrophilic nucleolar organizer regions in esophageal carcinoma. AB - The argyrophilic nucleolar organizer region (AgNOR) of 100 cancer cells from biopsy specimens of esophageal squamous cell carcinomas in 98 surgically treated cases was examined, using a silver colloid staining technique on biopsy specimens. The number of AgNOR per nucleus (AgNOR number) was higher in the more advanced groups with regard to the length of the tumor (P less than 0.01), the depth of penetration (P less than 0.05), and lymph node metastasis (P less than 0.01). The survival of the patients with a high AgNOR number (greater than or equal to 6) was significantly poorer than those with either a medium range AgNOR number (4 less than or equal to-less than 6) (P less than 0.05) or a low AgNOR number (less than 4) (P less than 0.01). In the multivariate analysis including conventional clinicopathological factors, the AgNOR number was found to be one of the independent and significant variables (P less than 0.01). Because the AgNOR method is simple and can be applied to paraffin-embedded sections, the AgNOR number may provide potential benefit in the pretherapeutic assessment of malignant potentiality in esophageal carcinoma. PMID- 1913657 TI - Prostratin, a nonpromoting phorbol ester, inhibits induction by phorbol 12 myristate 13-acetate of ornithine decarboxylase, edema, and hyperplasia in CD-1 mouse skin. AB - Pretreatment of CD-1 mouse skin with prostratin (12-deoxyphorbol 13-acetate) inhibited biological response to phorbol 12-myristate 13-acetate. The three responses examined were hyperplasia, induction of ornithine decarboxylase, and edema; the characteristics of inhibition depended on the specific response. Hyperplasia is the best short-term correlate of tumor promotion. Two or more pretreatments with 2.56 mumol (1 mg) prostratin, administered at intervals of 1-4 days, almost completely blocked the hyperplasia induced by phorbol 12-myristate 13-acetate applied 15 min to 6 h after the last pretreatment. Inducibility of hyperplasia was partially restored at 2 days and recovered by 4 days. Prostratin was more potent for inhibition of ornithine decarboxylase induction (50% inhibitory dose = 25.6 nmol) than it was for hyperplasia: the inhibition was largely attained by the first application, and the recovery from inhibition was slower (8 days). Edema was partially inhibited by prostratin (dose giving 50% of maximal inhibition = 512 nmol). We have previously demonstrated that prostratin is a protein kinase C activator. Our present results show that prostratin is a functional antagonist for a class of protein kinase C mediated responses. The findings emphasize the diversity of biological outcome for protein kinase C activators, presumably driven by the extensive heterogeneity in the protein kinase C pathway. PMID- 1913656 TI - Growth inhibition of oncogene-transformed rat fibroblasts by cocultured normal cells: relevance of metabolic cooperation mediated by gap junctions. AB - We have studied the proliferation of rat 208F cells (a derivative of Rat-1 cells) transformed by activated c-Ha-ras, v-fgr, v-raf, v-fms, or v-src oncogenes during cocultivation with an excess of early passage rat embryonic fibroblasts or immortal 208F cells. The total number and size of foci formed by oncogene transformed 208F cells were strongly reduced by cocultured normal fibroblasts. The extent of growth suppression of transformed foci appears to be dependent on the type of transforming oncogene and on the type of normal fibroblasts rather than on the extent of gap-junctional communication between transformed and normal cells. Total inhibition of fluorescent dye transfer between normal and transformed cells by the 3 beta-O-hemisuccinate of 18 alpha-glycyrrhetinic acid (18 alpha-carbenoxolone), an inhibitor of gap-junctional communication in human fibroblasts, did not prevent growth inhibition of transformed cells in the cocultivation assay. Since adjacent cells remained electrically coupled in the presence of this inhibitor it is possible that the strongly reduced metabolic cooperation, as indicated by the lack of fluorescent dye transfer, is sufficient for mediating the growth-inhibitory effect of normal fibroblasts. 208F cell conditioned medium, however, also caused strong growth inhibition of transformed derivatives, suggesting that the effect is in part mediated by release of stable growth inhibitor(s) from 208F cells. PMID- 1913658 TI - Experimental studies and preliminary clinical trial of vinorelbine-loaded polymeric bioresorbable implants for the local treatment of solid tumors. AB - Vinorelbine is a new 5' nor Vinca alkaloid, active by i.v. route, in various types of cancer disease such as non-small cell lung cancer and advanced breast cancer. In order to evaluate the possibility of using this drug for local treatment of cancer, Vinorelbine-loaded bioresorbable polymeric implants were prepared using a copolymer of D,L-lactic and glycolic acids (PLA 37.5 GA 25). According to the manufacturing process, the 1.2-mm-diameter cylindrical rods obtained had a drug content of 1, 5, or 20% (w/w) and released half of their content within about 6 days in vitro. In vivo release in rats was slower, half of the drug being released after about 14 days. A dose-dependent antitumoral effect was observed in mice (solid P388 leukemia model) when implants were administered into or in contact with the tumor. At highest drug loads and when administered soon after tumor implantation, Vinorelbine implants were more effective than i.v. administration (median survival time of treated animals related to untreated controls, greater than 360 versus 188). In dogs, results of toxicity experiments revealed that administration of implants in vital organs must be avoided. On the contrary, s.c. administration was well tolerated. A transient local necrosis was observed in the days following implantation, but normal skin was recovered after about 10 weeks. Thus, a clinical trial was conducted on patients with head and neck cancer; implantation of 20% loaded polymeric implants into the tumor sites succeeded in 8 of 9 patients. The sole failure was attributed to the unusual hardness of the tumor tissue. Except for a local transient inflammatory reaction (easily treated with nonsteroidal antiinflammatory agents), no other sign of toxicity was detected, and patients tolerated the device well. Fourteen days after implantation, patients underwent their planned surgery, and the implants were recovered. Residual drug content varied from 24 to 55%. In all cases, there was a clearly delimited necrotic area around the implant, ranging from 0.5 to 3.5 cm in diameter. In the smallest tumors, necrosis was also observed in the normal tissue inside this area. These results invite further studies to evaluate such drug-loaded polymeric implants. PMID- 1913659 TI - Establishment of Epstein-Barr virus-negative diffuse large cell lymphoma cell line with an 8;22 chromosomal translocation. AB - A new human B-cell lymphoma cell line was established from a pleural effusion of a patient with a diffuse large cell lymphoma which originated from an ileocecal tumor. The cell line, designated KAL-1, has been passaged 280 times over a period of 22 months. This cell line was successfully maintained in a chemically defined serum-free medium; its doubling time is approximately 24 h. Immunologically, the cells were demonstrated to express IgM lambda on the cell surface and to react with monoclonal antibodies to B-cell antigen including B1, B4, HLA-DR, and common acute lymphoblastic leukemic antigen but not with B2 and all the T-cell markers. Immunoglobulin gene analysis revealed rearrangements of both JH and C lambda. These data indicate that this cell line represents the B-cell lineage at the immature B-cell stage. This cell line was negative for Epstein-Barr virus nuclear antigen and had no detectable Epstein-Barr virus genome in cellular DNA. Chromosome analyses revealed that the cells carried an 8;22 chromosome translocation, reminiscent of variant type Burkitt's lymphoma. However, there was no histological evidence for Burkitt's lymphoma. Molecular studies showed that KAL-1 had deregulated high constitutive expression of c-myc. This cell line was demonstrated to be highly tumorigenic when injected into athymic nude mice. This tumor model should provide clues about the molecular mechanism involved in the pathogenesis of B-cell malignancy and appears to be a useful in vivo model for the study of molecular events during B-cell differentiation and therapeutic investigations. PMID- 1913660 TI - Genetic alterations of the p53 gene are a feature of malignant mesotheliomas. AB - A putative tumor suppressor gene, p53, has been shown to be altered in a variety of human tumor types. The primary mechanism of p53 inactivation is believed to be mutation of one allele followed by loss of the second allele. Malignant mesothelioma is a tumor that has been highly associated with exposure to asbestos fibers, which are known to cause chromosomal abnormalities in mesothelial cells. We have examined four mesothelioma cell lines for genetic abnormalities in p53. Cytogenetic analysis revealed that two of the four tumors had abnormalities (numerical and/or structural) of chromosome 17 (the locus of the p53 gene). Restriction fragment length polymorphism analysis using a chromosome 17p-specific probe (pYNZ22) revealed that two tumors had loss of heterozygosity in the region of 17p13. The relative level of p53 mRNA expression was examined by Northern analysis, with one tumor showing negligible expression of p53 mRNA. The complementary DNA of p53 was generated from the three tumors showing detectable mRNA expression, and the region between codons 70 and 319 was amplified by the polymerase chain reaction and sequenced. DNA single-base substitutions were detected in two of the tumor cell lines, each resulting in amino acid substitutions. One tumor had an arginine to histidine substitution at position 175, and one tumor had a glycine to aspartic acid substitution at position 245. The observed mutations took place in regions of high cross-species sequence homology, indicating that these regions may be functionally important. The correlation of chromosomal loss in 17p on the cytogenetic and molecular level along with p53 mRNA expression and DNA sequence data indicate that genetic alterations in p53 could be a feature of malignant mesotheliomas and may reveal an important role of asbestos fibers in tumor suppressor gene inactivation. PMID- 1913661 TI - Antitumor immune response and interleukin 2 production induced in colorectal cancer patients by immunization with human monoclonal anti-idiotypic antibody. AB - The immunogenicity of human anti-idiotypic antibody has been investigated using a human monoclonal anti-idiotypic antibody (105AD7) which interacts with the binding site of 791T/36, a mouse monoclonal antibody against gp72 antigen. This antigen is frequently expressed in gastrointestinal cancer, therefore, six patients with advanced colorectal cancer have been immunized with 105AD7 as an aluminum hydroxide gel precipitate in a phase I clinical study. Cryopreserved blood mononuclear cells were tested for in vitro proliferative responses by [3H]thymidine incorporation; plasma samples were tested by enzyme-linked immunosorbent assay for anti-anti-idiotypic and antitumor antibodies, and for interleukin 2. Proliferative responses to gp72 positive tumor cells were seen in four of five patients tested; parallel in vitro responses to 105AD7 anti idiotypic antibody were seen in most of these patients. Interleukin 2 was detected in the plasma of four of six patients after 105AD7 immunization, with peak levels up to 7 units/ml. No toxicity related to anti-idiotype immunization and no antitumor or anti-anti-idiotype antibodies were seen. This study shows that human monoclonal anti-idiotype 105AD7 is immunogenic in cancer patients, inducing cellular antitumor responses and interleukin 2 production. This suggests that human monoclonal anti-idiotype antibodies may have considerable potential for immunotherapy of human cancer. PMID- 1913662 TI - Correspondence re: O. C. A. Scott, tumor transplantation and tumor immunity: a personal view. Cancer Res., 51: 757-763, 1991. PMID- 1913663 TI - Workshop report from the Division of Research Grants, National Institutes of Health. The role of chromosome rearrangements, deletions, and point mutations in cancer--a Pathology B Study Section workshop. PMID- 1913664 TI - Potentiation of mitomycin C and porfiromycin antitumor activity in solid tumor models by recombinant human interleukin 1 alpha. AB - The time- and dose-dependent effects of recombinant human interleukin 1 alpha (IL 1 alpha) on the antitumor activity of mitomycin C (MMC) and porfiromycin (PORF) were studied in RIF-1 and Panc02 solid tumor model systems. IL-1 alpha produced dose-dependent sensitization of clonogenic RIF-1 tumor cells to MMC in vivo. IL-1 alpha chemosensitization was highly schedule dependent, and the most efficacious schedules produced dose-modifying factors of 3.6 and 5.1 for MMC and PORF, respectively. More than additive clonogenic cell kill after IL-1 alpha chemotherapy combinations reflected increased cellular sensitivity to MMC and PORF. The combinations also produced marked decreases in the yield of viable tumor cells, suggesting that the bioreductive drugs may have also potentiated the microvascular injury and ischemia produced by IL-1 alpha. Dexamethasone inhibited and ketoconazole, an inhibitor of corticosterone biosynthesis, enhanced IL-1 alpha-mediated chemosensitization in these models. IL-1 alpha mediated chemosensitization to MMC, and PORF was also demonstrated by tumor growth inhibition in the RIF-1 model and increased survival of mice in the spontaneously metastasizing Panc02 system. Chemosensitization of bone marrow spleen colony forming units was not seen. IL-1 alpha (1000 units/ml) had no effect on MMC and PORF cytotoxicity in RIF-1 and PORF cell lines in vitro. The results indicate that the tumor-specific IL-1 alpha-induced pathophysiologies can sensitize solid tumors to agents which are preferentially activated, retained, and cytotoxic to cells under hypoxic conditions. Our results suggest that strategies combining bioreductively activated hypoxic cell cytotoxins and biological agents might offer efficacious alternatives or adjuvants to conventional combination approaches. PMID- 1913665 TI - Pharmacokinetics and immune response of 131I-chimeric mouse/human B72.3 (human gamma 4) monoclonal antibody in humans. AB - Chimeric B72.3, composed of the V-regions of murine B72.3 and the constant regions of human immunoglobulin G4 heavy and kappa light chain, was administered as a 131I-labeled conjugate to 12 patients with metastatic colon cancer. Seven of these patients had an antibody response after initial infusion, and the immune response was primarily directed to the murine V-region, although a small proportion of the antibody response was directed to topographical epitopes requiring the presence of both murine V-region and human CH-1 and kappa constant regions (neo-epitopes). The pharmacokinetics included a plasma disappearance curve best fit by a two-compartmental model with an alpha t 1/2 of 18 +/- 7 h and a beta t 1/2 of 224 +/- 66 h. A second infusion of the same dose of 131I-chimeric B72.3 was administered to four of these patients 8 wk after the first infusion. Two patients who had a high antibody response to initial infusion had an anamnestic antibody response, and the infused ch-B72.3 rapidly disappeared from the circulation with associated immune complexes and free 131I in the plasma. One patient with no initial antibody response had no antibody response and identical pharmacokinetics on second infusion. One patient with a modest transient antibody response to initial infusion had no antibody response on second infusion and a modest shortening of plasma circulation. Thus, the human immunoglobulin G4 isotype chimeric B72.3 monoclonal antibody has a plasma half-life 6 to 8 times as long as murine B72.3 and retains considerable immunogenicity in some patients which can adversely affect repetitive infusions. PMID- 1913666 TI - Pharmacokinetics of pyrazoloacridine in the rhesus monkey. AB - Pyrazoloacridine is a rationally synthesized acridine derivative with in vitro activity against solid tumor cell lines, noncycling and hypoxic cells, and tumor cell lines that exhibit the multidrug resistance phenotype. The pharmacokinetic behavior of pyrazoloacridine after a 1- or 24-h i.v. infusion was studied in 5 rhesus monkeys that received a total of 10 courses of pyrazoloacridine at 300 or 600 mg/m2. Pyrazoloacridine levels in plasma and cerebrospinal fluid were measured by high-pressure liquid chromatography. For 1-h infusions, the plasma disappearance was biexponential with a t 1/2 alpha of 31 min and t 1/2 beta of 11 h. The mean volume of distribution at steady state was 1380 liters/m2. The clearance was 1660 ml/min/m2. For the 300 mg/m2 dose, the mean area under the concentration-time curve was 759 microM.min, and the mean peak concentration was 1.3 microM. For the 600 mg/m2 dose, the area under the concentration-time curve was 1330 microM.min, and the peak concentration was 2.5 microM. The steady-state plasma concentrations during the 24-h continuous infusions were 0.27 microM for the 300 mg/m2 dose and 0.45 microM for the 600 mg/m2 dose. The mean clearance calculated from these steady-state concentrations was 2420 ml/min/m2. Cerebrospinal fluid levels were less than 0.1 microM for all doses and schedules. There was no evidence of toxicity at any dose or schedule. These results contrast strikingly with those obtained in mice and dogs in which, despite a more rapid clearance of pyrazoloacridine, significant toxicities were observed at doses that were nontoxic in the monkey. These interspecies differences in the pharmacokinetic and pharmacodynamic behavior of pyrazoloacridine have important implications for the design of Phase I trials in humans. PMID- 1913667 TI - Epidermal growth factor receptor-reactive monoclonal antibodies: xenograft antitumor activity alone and as drug immunoconjugates. AB - Antibodies reactive with human epidermal growth factor receptor (EGFr), such as 225 IgG1 (Masui et al., Cancer Res., 44: 1002-1007, 1984), are effective tumor suppressive agents in xenograft models. In the present study an additional antibody reactive with EGFr was made and compared to 225 IgG1 for antitumor activity as an unmodified antibody or as a drug immunoconjugate. This IgG1 clone, designated EGFrL11, competed with EGF and immunoprecipitated a Mr 178,000 protein identical to that immunoprecipitated with 225 IgG1. Cross-competition and immunodepletion studies indicated that the two antibodies bound to distinct epitopes on the same molecule. Immunofluorescence studies confirmed that the EGFrL11 epitope was expressed on the surface of viable human squamous cell carcinoma lines including T222. Unmodified EGFrL11 and 225 IgG1 were tested for antitumor activity in T222 xenografts. At a dose of 81 mg/kg given twice weekly for 3 weeks, tumor suppression, but not regression, occurred with EGFrL11. A similar result was obtained with 225 IgG1. To gauge the potential of these antibodies as immunoconjugates, both were tested for antitumor activity in the T222 model after conjugation to the Vinca derivative 4-desacetylvinblastine-3 carboxhydrazide. Both immunoconjugates completely regressed established tumors. These data suggest that Vinca conjugates with EGFr-reactive monoclonal antibodies warrant further investigation as possible clinical candidates. PMID- 1913668 TI - Tumor-promoting effect of urinary epidermal growth factor in rat urinary bladder carcinogenesis. AB - We previously demonstrated that the specific component of rat urine designated as Fraction I (Fr.I), which has been known to enhance carcinogenesis in the rat urinary bladder, contains epidermal growth factor (EGF) and transferrin (TF). The present study was designed to determine whether EGF or TF is responsible for the tumor-enhancing effect of Fr.I. The heterotopically transplanted rat urinary bladder (HTB), which has been developed in our laboratory, was used for the study. Fr.I was prepared from normal rat urine by a method published previously. Fr.I deficient in EGF or TF was prepared by passing this fraction through an Affi Gel Hz column coupled with anti-rat EGF or TF antibodies, respectively. EGF and TF eluted from the column (designated as eluted EGF and eluted TF) were also tested for tumor-enhancing activity. Fr.I passed through the column coupled with nonimmune rabbit IgG served as control (Fr.I column control). After initiation of carcinogenesis in HTBs by instillation of a single dose of 0.25 mg of N-methyl-N nitrosourea, test materials were administered into these HTBs once a week for 30 weeks. The results showed that removal of EGF significantly reduced the tumor enhancing effect of Fr.I (P less than 0.001 as compared to that of the Fr.I column control) and that eluted EGF by itself significantly enhanced the carcinogenesis as compared to that of the vehicle control (P less than 0.006). Removal of TF from Fr.I also reduced the tumor-enhancing effect of Fr.I (P less than 0.01). However, removal of both EGF and TF from Fr.I did not enhance the inhibitory effect demonstrated by the Fr.I which was deficient in EGF. Likewise, combined use of TF and EGF did not exceed the tumor-promoting effect of EGF. The results indicate that EGF in Fr.I may play a significant role in the promotion of bladder carcinogenesis by urine. PMID- 1913669 TI - Differential expression of transforming growth factor-beta 1 gene in 3LL metastatic variants. AB - In vitro and in vivo metastatic variants derived from Lewis lung carcinoma (3LL) were examined for the level of the expression of several growth-regulated genes, oncogenes, and transforming growth factor (TGF) genes. To determine whether the proliferative advantage of metastatic cells is due to an increased growth fraction of the cell population or to a deregulated expression of some growth regulated genes, the mRNA levels of the S-phase-specific H3 histone gene were compared with that of some cell cycle-related genes (vimentin, calcyclin, c-myc, and p53) and oncogenes (Ki-ras, Ha-ras, c-sis, c-src, c-fes, and c-erb). In addition, to evaluate whether an autocrine pattern of cell proliferation is responsible for the proliferative advantage of metastatic cells, the level of the expression of TGF genes (alpha and beta 1) was studied. Northern blot analysis demonstrated that in 3LL metastatic variants the expression of TGF-alpha as well as the expression of all growth-regulated genes and oncogenes studied are similar. Only the TGF-beta 1 gene is expressed at higher levels in highly metastatic 3LL variants maintained either in vitro or in vivo. Data suggest that the proliferative advantage of 3LL metastatic cells is not due to a deregulated expression of some growth-regulated genes and oncogenes, but more likely is acquired through the expression of genes which might interfere with the ability of the tumor cells to escape hostile microenvironmental conditions. PMID- 1913670 TI - Quantitation of microsomal alpha-hydroxylation of the tobacco-specific nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. AB - 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is activated to DNA alkylating species via two different alpha-hydroxylation pathways. Methylene hydroxylation leads to DNA methylation, whereas methyl hydroxylation yields DNA pyridyloxobutylation. We have developed a high-pressure liquid chromatography assay utilizing radiochemical detection that permits the determination of the extent of metabolism through each pathway in microsomal preparations. Levels of 4 hydroxy-1-(3-pyridyl)-1-butanone (HPB) were used to measure the extent of methyl hydroxylation, whereas levels of the aldehyde, 4-oxo-1-(3-pyridyl)-1-butanone (OPB), were used to quantify the extent of methylene hydroxylation. Incubations of [5-3H]NNK with microsomes and cofactors were conducted in the presence of 5 mM sodium bisulfite to trap the reactive OPB. The inclusion of bisulfite did not affect the rate of NNK metabolism. Trapping the aldehyde also inhibited its further oxidation to the corresponding acid or reduction to HPB. Furthermore, the conversion of HPB to OPB made only a minor contribution to the OPB levels under our incubation conditions. Analysis of incubation mixtures containing [5-3H]NNK, cofactors, and either A/J mouse liver or lung microsomes demonstrated that OPB was a significant metabolite of NNK. The OPB:HPB ratio was greater in liver (1.5) than in lung (0.2-1) microsomal preparations. Apparent Km values for OPB and HPB formation in lung microsomes were 23.7 and 3.6 microM, respectively, whereas the corresponding values for liver microsomes were 19.1 and 73.8 microM, respectively. These data are consistent with the involvement of more than one cytochrome P-450 isozyme in the activation of NNK to DNA reactive species. PMID- 1913671 TI - Down-regulation by interleukin 4 of activation of human alveolar macrophages to the tumoricidal state. AB - The effect of recombinant human interleukin 4 (IL-4) on the expression of antitumor activity of human alveolar macrophages (AM) obtained by bronchoalveolar lavage from healthy donors was examined. AM were incubated for 16 h in medium with various macrophage activators [lipopolysaccharide, des-methyl muramyldipeptide, Nocardia rubra cell wall skeleton, and heptanoyl-gamma-D-Glu (L)-meso-alpha,epsilon-A2pm(L)-D-Al aOH] in the presence or absence of IL-4, and then their tumoricidal activity was assayed by measuring 125I-UdR release from human melanoma (A375) cells. The spontaneous tumoricidal activity of AM was slightly suppressed by IL-4 in 3 of 7 donors. Addition of IL-4 to cultures of AM with the activators resulted in dose-dependent suppression of AM-mediated cytotoxicity against A375 cells. IL-4 also inhibited AM-mediated cytotoxicity against A375-R cells, which are resistant to interleukin 1 (IL-1) and tumor necrosis factor alpha, HT-29 colon cancer cells, and KB cells. IL-4 inhibited the early induction phase of AM activation. Pretreatment of AM with IL-4 also suppressed their expression of antitumor activity in response to lipopolysaccharide. IL-4 inhibited the production of monokines (IL-1 and tumor necrosis factor alpha) by AM at the protein and mRNA levels. These findings suggest that IL-4 may be important in vivo in the down-regulation of antitumor expression of AM in the lung by inhibiting the production of monokines and other killing mechanisms. PMID- 1913672 TI - Human fibroblasts contain a proteolytic activity which is inhibited by the Bowman Birk protease inhibitor. AB - The Bowman Birk protease inhibitor (BBI) has been shown to be an effective suppressor of carcinogenesis in vivo and in vitro. In this report we demonstrate that normal human fibroblasts and Bloom cells contain a BBI-inhibitable proteolytic activity. The enzyme cleaves gelatin, has a molecular mass of 43 kDa, and is located in the cytosol. This activity has maximal activity at pH 8 and was inhibited by diisopropylfluorophosphate but was not affected by EDTA or 1,10 phenanthroline, indicating that this enzyme is a serine protease. We have reported previously that a similar BBI-inhibitable activity is present in C3H/10T1/2 mouse embryo fibroblast cells. Our results suggest that a common "target enzyme" of the BBI is present in mouse and human cells. PMID- 1913673 TI - Insensitivity to the cytolytic effects of glucocorticoids in vivo is associated with a novel "slow death" phenotype. AB - Tumors formed from wild type P1798 mouse lymphoma cells undergo regression when treated with pharmacological doses of natural and synthetic glucocorticoids in vivo. Variants have been selected that are insensitive to the cytolytic effects of glucocorticoids in vivo. Although the response of wild type and insensitive tumors is markedly different in vivo, the manner in which cells from such tumors respond to glucocorticoids is indistinguishable in culture under routine conditions. Glucocorticoids inhibit proliferation of wild type cells as well as those that are insensitive to glucocorticoids in vivo. Although neither cell line dies when exposed to dexamethasone in culture in the presence of fetal bovine serum, both sensitive and insensitive cell lines undergo cytolysis when exposed to dexamethasone in serum-free medium. Sensitive cells die more quickly, with 50% cell death observed within 6 h. Insensitive cells exhibit less than 10% cell death within 6 h. Sensitive cells continue to die after transitory exposure to dexamethasone, whereas insensitive cells do not. Thus, growth in serum-free medium mimics the response that prevails in vivo. Cell death is associated with rapid, internucleosomal chromatin degradation. The rate of DNA fragmentation is comparable to that of cell death. About 30% of the DNA in sensitive cells is degraded to fragments of less than 10 kilobases within 2 h after addition of dexamethasone, and 70-80% of the DNA is degraded within 6 h. There is no significant degradation observed when insensitive cells are treated for 6 h. P1798 cell lines express an endonuclease that is capable of degrading chromatin in vitro. Basal expression of this activity does not correlate with glucocorticoid sensitivity, and insensitivity does not appear to be attributable to a decrease in expression of the enzyme(s) thought to be responsible for glucocorticoid-mediated chromatin degradation. The data suggest that glucocorticoid insensitivity is associated with delayed activation and/or induction of some lytic principle. Alternatively, resistance may be due to enhanced ability to repair the damage induced by transitory exposure to glucocorticoids in vivo. PMID- 1913674 TI - Glucocorticoid insensitivity of P1798 lymphoma cells is associated with production of a factor that attenuates the lytic response. AB - P1798 murine lymphoma cells die when exposed to glucocorticoids in vivo. Such cells are sensitive to glucocorticoids in culture in serum-free medium, and 80 90% of wild type cells will die within 24 h after addition of 0.1 microM dexamethasone. However, addition of fetal bovine serum prevents cell death in culture. Variants that were selected for resistance to the cytolytic effects of glucocorticoids in vivo are relatively insensitive to dexamethasone in culture. Insensitive variants die more slowly than wild type cells, with 10-20% cell death observed within 24 h after addition of dexamethasone. Conditioned medium from insensitive cultures protects wild type P1798 cells from dexamethasone in serum free medium. Such medium contains one or more factors that attenuate the lytic response. This lysis resistance factor(s) has the properties of a protein and may be a growth factor. Expression of the lysis resistance factor(s) appears to be regulated by glucocorticoids. These studies define an heretofore uncharacterized mechanism whereby the ability of malignant lymphoid cells to elaborate and/or respond to an autocrine factor(s) influences the extent to which such cells die when exposed to glucocorticoids in culture and probably in vivo. PMID- 1913675 TI - O6-methylguanine is a critical determinant of 4-(methylnitrosamino)-1-(3-pyridyl) 1-butanone tumorigenesis in A/J mouse lung. AB - The relative importance of the two alpha-hydroxylation pathways in the tumorigenicity of the tobacco-specific nitrosamine, 4-(methylnitrosamino)-1-(3 pyridyl)-1-butanone (NNK), was examined in the A/J mouse lung. Methyl hydroxylation, which results in DNA pyridyloxobutylation, was investigated with 4 (acetoxymethylnitrosamino)-1-(3-pyridyl)-1-butanone (NNKOAc) and N' nitrosonornicotine. Methylene hydroxylation, which leads to DNA methylation, was studied by using acetoxymethyl-methylnitrosamine (AMMN). The tumorigenic activities of these compounds were compared to that of 10 mumol NNK at doses that yielded similar or greater adduct levels 24 h after exposure. The methylating agent AMMN was more tumorigenic than the pyridyloxobutylating agents, NNKOAc and N'-nitrosonornicotine. NNKOAc enhanced the tumorigenic activity of AMMN when the two compounds were given in combination. These results suggested that DNA methylation was more important than DNA pyridyloxobutylation in A/J mouse lung tumor induction by NNK and that pyridyloxobutylation enhanced the activity of the methylation pathway. However, the tumorigenicity of 10 mumol NNK could not be reproduced by AMMN +/- NNKOAc at doses that yielded similar levels of DNA adducts 24 h after exposure. Therefore, a second study was conducted in which the persistence of O6-methylguanine in lung DNA following various doses of NNK or AMMN +/- NNKOAc was compared to the tumorigenicity of these treatments. A strong correlation was observed between lung tumor yield and levels of O6-methylguanine at 96 h for NNK and AMMN +/- NNKOAc (r = 0.98). The ability of NNKOAc to increase the tumorigenic activity of AMMN was attributed to its ability to enhance the persistence of O6-methylguanine in lung DNA. These results demonstrate that the formation and persistence of O6-methylguanine are critical events in the initiation of A/J mouse lung tumors by NNK. They also suggest that DNA pyridyloxobutylation by NNK can increase the persistence of this promutagenic base in lung DNA. PMID- 1913676 TI - ICI D1694, a quinazoline antifolate thymidylate synthase inhibitor that is a potent inhibitor of L1210 tumor cell growth in vitro and in vivo: a new agent for clinical study. AB - N-(5-[N-(3,4-dihydro-2-methyl-4-oxoquinazolin-6-ylmethyl)-N- methylamino]-2 thenoyl)-L-glutamic acid (ICI D1694) is a water-soluble, folate-based thymidylate synthase (TS) inhibitor designed to be a less toxic and more potent analogue of the clinically tested N10-propargyl-5,8-dideazafolic acid. Inhibition of isolated L1210 TS by ICI D1694 is mixed noncompetitive (although tending toward competitive), with a Ki of 62 nM (Kies = 960 nM). The synthetic gamma polyglutamates are up to 2 orders of magnitude more potent as inhibitors of TS; e.g., the tetraglutamate (glu4) has a Ki of 1.0 nM (Kies = 15 nM). Although inhibitory activity of ICI D1694 toward rat liver dihydrofolate reductase was similar to that of TS (Ki = 92 nM; competitive inhibition) the polyglutamate derivatives did not show enhanced activity. ICI D1694 was also a very potent inhibitor of L1210 cell growth (50% inhibitory activity = 8 nM). L1210 growth inhibition was not observed in the presence of thymidine, consistent with TS being the locus of action. Folinic acid antagonized L1210 growth inhibition in a competitive fashion such that the highest folinic acid concentration used (25 microM) increased the 50% inhibitory activity 6000-fold. When given as a 4-h delayed "rescue", folinic acid was much less effective in antagonizing growth inhibition. These observations are consistent with folinic acid competing with ICI D1694 for uptake into the cell and/or intracellular polyglutamation. The L1210:1565 cell line, which has greatly impaired reduced-folate/methotrexate transport and thus is resistant to methotrexate, was significantly cross resistant to ICI D1694 (121-fold), suggesting that ICI D1694 is dependent on this uptake mechanism for good cytotoxic potency in L1210 cells. L1210 cells that were incubated for 4 h with 0.1 microM 3H-ICI D1694 accumulated approximately 1.5 microM intracellular 3H, and the high performance liquid chromatography analysis of the cell extracts demonstrated that 96% of the 3H was associated with the ICI D1694 polyglutamate fractions (principally glu4). Upon resuspension in drug-free medium for 24 h, approximately 75% of the cellular 3H was retained, this being the higher polyglutamate pool (glu4-6). In mice, after a single bolus injection of 10 mg/kg of ICI D1694, TS was inhibited greater than 80% for 24 h in ascitic L1210:NCI cells (as measured by the rate of 3H release from [5-3H]deoxyuridine). ICI D1694 cured the L1210:ICR ascitic tumor in mice at 0.4 mg/kg daily for 5 days (maximum tolerated dose, approximately 50 mg/kg).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1913677 TI - Induction of tissue-type plasminogen activator by ionizing radiation in human malignant melanoma cells. AB - Two differently timed extracellular and intracellular enzymatic and mRNA peaks of tissue-type plasminogen activator (t-PA) were induced following ionizing radiation. The first peak appeared within 10 min following X-irradiation but rapidly declined. The appearance of early t-PA mRNA transcripts and enzymatic activity were not prevented by actinomycin D treatment. In contrast, cycloheximide prevented the early, minor enzymatic induction peak of t-PA. Stabilization of t-PA mRNA transcripts appears to be an early initial response of human cells to ionizing radiation, since the synthesis of new mRNA transcripts within the first 30 min was not observed via nuclear run-on analyses. Nearly 12 h following X-irradiation, a second major enzymatic peak of t-PA was observed. Cycloheximide or actinomycin D treatments blocked the later t-PA response. t-PA mRNA levels were induced greater than 100-fold in 4 h by ionizing radiation as assayed via Northern or nuclear run-on analyses. During the major induction period, t-PA mRNA transcripts reached their maximum levels at 4-8 h, and intracellular enzyme levels accumulated 6-8 h after X-irradiation. Unirradiated U1-Mel cells demonstrated only low basal levels of t-PA mRNA and enzymatic activity. Similar induction responses were found following UV-irradiation or 12-O tetradecanoyl-phorbol-13-acetate (PMA) treatments. Normal human fibroblast (i.e., GM 2936B, GM2907A, and IMR-90) cells also demonstrated the induction of t-PA, although only one later enzymatic peak was detected. The induction of t-PA mRNA levels and intracellular and extracellular enzymatic activities for these cells were 50-fold lower than with U1-Mel cells given equitoxic doses of X-rays. Differential expression of t-PA in some tumor as compared to normal tissues may be utilized in future chemotherapeutic regimens. PMID- 1913678 TI - Dietary calcium and vitamin D modulate 1,2-dimethylhydrazine-induced colonic carcinogenesis in the rat. AB - To determine whether supplemental dietary calcium and/or vitamin D deficiency are involved in modulating colon cancer induced by 1,2-dimethylhydrazine (DMH), Sprague-Dawley rats were fed diets containing either: (a) a normal content of calcium (0.87%) and phosphorus (0.60%) with 2.2 IU of vitamin D3 per g of feed (group A); (b) the same diet as group A, but with calcium and phosphorus increased to 1.80 and 0.80%, respectively (group B); or (c) a vitamin D-deficient diet with supplemental calcium (1.80%) and phosphorus (0.80%) (group C). After 6 weeks on their respective diets, one-half the animals in each group were given s.c. injections of either vehicle or DMH (20 mg/kg body weight/week) for 26 weeks. Animals were then sacrificed and the incidence of tumors as well as the number of tumors per tumor-bearing rat were determined. Colonic mucosal polyamine levels were measured after 15 weeks of exposure to vehicle or DMH, before development of histologically recognizable neoplasms. The results of these experiments demonstrated that neither calcium supplementation alone nor supplemental calcium in conjunction with vitamin D deficiency altered the incidence of colonic cancer induced by this carcinogen. Supplemental calcium, however, significantly decreased the number of rats with multiple tumors and reduced tumor size. Moreover, vitamin D deficiency abolished these protective effects of calcium on colon cancer in this experimental model. DMH treatment increased polyamine levels in the premalignant colonic mucosa in group A rats. This carcinogen-induced effect was blunted by high dietary calcium. Vitamin D deficient, calcium-supplemented rats (group C) showed an increase in N1 acetylspermidine, but not the other polyamines, with DMH treatment. PMID- 1913679 TI - Use and mechanism of action of AS101 in protecting bone marrow colony forming units-granulocyte-macrophage following purging with ASTA-Z 7557. AB - Ammonium trichloro(dioxoethylene-O,O')tellurate (AS101) has been shown previously to provide radioprotective effects when given to mice 24 h prior to irradiation and to protect mice from lethal and sublethal doses of cyclophosphamide (CTX). In this study we examined the ability of AS101 to protect mice bone marrow colony forming units-granulocyte-macrophage treated in vitro with various doses of ASTA Z 7557, a potent derivative of cyclophosphamide. We demonstrate that prior incubation with AS101 protects colony forming units-granulocyte-macrophage from toxic effects of ASTA-Z. This protection can also be conferred by injection of mice with AS101 prior to incubation of their bone marrow in vitro with ASTA-Z. Prior incubation with AS101 was shown not to protect K562 leukemic cells or HL-60 cells from the toxic effects of ASTA-Z. We show that AS101 protection from the toxic effects of ASTA-Z in vitro and CTX in vivo can be partially ascribed to increased aldehyde dehydrogenase (ALDH) activity induced by AS101. This was shown directly by measuring cellular ALDH activity and indirectly by measuring the toxicity of ASTA-Z and CTX in the presence of cyanamide, an inhibitor of ALDH. AS101 is also demonstrated in this study to protect spleen cells from the toxic effects of 5-fluorouracil, probably through a different mechanism. These properties of AS101 make it a useful candidate for increasing the qualitative potential of bone marrow used for autologous transplantation after purging with ASTA-Z. In addition, the results suggest an increase in ALDH activity by AS101 as one of the mechanisms of protection from the toxic effects of ASTA-Z and CTX. However, the chemoprotectiveness of AS101 was found not to be restricted to cyclophosphamide, since as shown in this study, AS101 helped by other mechanisms to reconstitute the number of spleen cells after 5-fluorouracil treatment. PMID- 1913680 TI - Allelic loss on chromosome 17p and p53 mutations in human endometrial carcinoma of the uterus. AB - To understand the involvement of allelic losses and inactivation of tumor suppressor genes for the development of endometrial carcinoma of the uterus (EC), 24 cases of EC were examined for loss of heterozygosity (LOH) using a total of 57 polymorphic DNA markers covering all 23 pairs of chromosomes. LOH was observed at 27 loci on 10 different chromosomes, i.e., chromosomes 1, 3, 6, 11, 13, 15, 17, 18, 20, and 21, but was not detected at loci on chromosomes 4, 5, 7, 9, 10, 12, 14, 16, and X. It was observed only in seven of 24 cases, and the other 19 cases did not show LOH at any loci examined, including five cases of tumors with a high proportion of adenomatous hyperplasia. Among seven tumors with LOH at one or more loci, five tumors showed LOH at loci on the short arm of chromosome 17. Furthermore, mutations of the p53 gene, which is located on the short arm of chromosome 17, were detected in three of these 24 tumors by a polymerase chain reaction-single strand conformation polymorphism analysis and subsequent DNA sequencing. In two of these three tumors, p53 mutations were accompanied by the loss of wild-type p53 alleles. These results suggest that inactivation of the p53 gene is involved in the development of EC as in the case of several other types of human cancers. PMID- 1913681 TI - Formation and persistence of DNA adducts of 2-amino-3-methylimidazo[4,5-f] quinoline in male Fischer-344 rats. AB - The mutagenic heterocyclic amine 2-amino-3-methylimidazo[4,5-f] quinoline (IQ) is carcinogenic in the Fischer-344 rat, affecting the liver and small and large intestines, as well as several other organs. In male animals the incidences of tumors in the liver, small intestine, and large intestine were reported to be 67.5, 30.0, and 62.5%, respectively. Using 32P-postlabeling assays, the formation and persistence of IQ-DNA adducts in the liver and small and large intestines were studied in male Fischer-344 rats. Young, adult animals were either given a single p.o. dose (5, 25, or 50 mg/kg) of IQ and were killed 24 h later or were given a single p.o. or i.p. dose (50 mg/kg) of IQ and were killed at different time points, from 6 h to 31 days after p.o. treatment and from 6 h to 6 days after i.p. treatment, to follow adduct persistence. Up to five specific adducts could be isolated, and adduct formation was dose related in all three organs. Adduct 1, previously shown to be N-(hydroxyguanosin-8-yl)-IQ, was the major adduct in all cases, comprising up to 78% of the total. After p.o. administration (6-24 h) adduct levels in the liver were 3- to 4-fold higher than after i.p. administration, while levels in the intestines during this time period were independent of the route of administration. At 24 h after p.o. administration total adduct levels in the liver were 13.5-41.4 and 9.2-18.4 times higher than those in the small intestine and large intestine, respectively. Maximum adduct levels were observed between 6 and 24 h after administration, and from 1 to 6 days later, rates of removal from the liver were 7-fold and 2-fold slower, respectively, than from the small and large intestine. Rates of adduct removal from the intestines after i.p. administration were similar to those after p.o. administration. Beyond day 15 adduct levels in all organs constituted less than 12% of those on day 1, and low levels of adducts persisted for up to 31 days. In all cases there was no preferential loss or persistence of any of the adducts. It is concluded that total adduct levels and persistence in target organs may, in part, be related to susceptibility to IQ-induced carcinogenesis in the Fischer 344 rat. PMID- 1913682 TI - Tumor-promoting activity of ethyl phenylpropiolate. AB - The ability of the hyperplasiogenic irritant ethyl phenylpropiolate (EPP) to act as a tumor promoter in two-stage carcinogenesis and to stimulate cellular events commonly cited as markers of tumor promoter action was evaluated. Treatment of adult, inbred SENCAR (SSIN) mice, initiated with 7,12-dimethylbenz(a)anthracene, with 5 mg of EPP twice weekly resulted in 100% of the mice developing tumors (4.8 tumors/mouse) after 40 weeks of promotion. Treatment with 3 mg EPP (twice weekly) resulted in 52% of the mice developing tumors (0.9 tumor/mouse). This treatment regimen with EPP produces a sustained epidermal hyperplasia without being overtly toxic. In addition, a 5-mg dose of EPP induced ornithine decarboxylase activity to a level comparable to that induced by the tumor promoter phorbol 12-myristate 13-acetate (PMA): 2.3 nmol CO2/mg protein/h for EPP versus 4.5 nmol CO2/mg protein/h for PMA versus 0.04 nmol CO2/mg protein/h for acetone control. Likewise, the time course of ornithine decarboxylase induction by EPP was the same as that seen with PMA (maximum induction at approximately 6 h). Vascular permeability of the dorsal skin increased significantly in response to EPP (8 times that seen in acetone controls) and exhibited the same kinetics as that seen after exposure to PMA. Activity of protein kinase C (PKC), the cellular receptor for PMA, decreased by 75 to 95% 48 h after treatment with PMA. In contrast, EPP treatment resulted in less than a 20% decrease in PKC activity 48 h after treatment. This slight decrease in PKC activity is thought to be an indirect effect caused by the hyperproliferative and inflammatory reactions, because EPP was found to be inactive as an in vitro activator of PKC. These results indicate not only that EPP is a good tumor promoter that causes morphological and biochemical responses similar to those induced by PMA, but also that the action of EPP is apparently mediated via a mechanism that does not involve direct interaction with PKC. PMID- 1913683 TI - Frequent induction of mammary carcinomas following neu oncogene transfer into in situ mammary epithelial cells of susceptible and resistant rat strains. AB - Varying results have been reported on the role of neu oncogene in mammary carcinogenesis. In order to further address this issue, the activated neu oncogene was introduced into mammary epithelial cells in situ of both mammary carcinoma-susceptible Wistar Furth and resistant Copenhagen rats by infusing replication-defective recombinant retroviruses carrying the neu oncogene into the mammary gland lumen. At the highest virus titer tested, very high numbers of mammary carcinomas developed within 2 weeks in all exposed glands in both rat strains. When the virus titer was reduced, however, individual tumors occurred with varying latencies. In addition, not all of the neu-infected mammary cells progressed to form mammary carcinomas. These results suggest that while neu is a potent mammary transforming gene, either other events in addition to neu expression may be required for full malignant transformation or not all mammary ductal epithelial cells are able to be neoplastically transformed. PMID- 1913684 TI - Forestomach and kidney carcinogenicity of caffeic acid in F344 rats and C57BL/6N x C3H/HeN F1 mice. AB - The carcinogenic potential of caffeic acid was investigated in both sexes of F344 rats and C57BL/6N x C3H/HeN F1 mice. After groups of 30 animals received diet containing 0 and 2.0% caffeic acid for 104 weeks in rats or 96 weeks in mice, detailed histopathological examination revealed induction of forestomach squamous cell papillomas or carcinomas in rats at high incidence (77% for males; 80% for females) and in mice at low incidence (13% for males; 3% for females). Invasion to the abdominal cavity of these squamous cell carcinomas was observed in three rats and two mice. In addition, renal tubular cell hyperplasias and adenomas, clearly related to toxic lesions, were found in treated rats at high incidence for males (73 and 13%) and low incidence for females (20 and 0%). In mice, renal tubular cell hyperplasias and tumors also occurred in treated females (97 and 28%), and at a lower incidence in treated males (27 and 3%). No toxic renal injuries were apparent in mice. Alveolar type II cell tumors also developed in treated male mice (27%) with statistical significance. Thus, the current investigation showed caffeic acid to exert carcinogenic activity for the forestomach squamous cell epithelium in both sexes of F344 rats and C57BL/6N x C3H/HeN F1 mice, for the renal tubular cell in male rats and female mice, and for the alveolar type II cell in male mice. PMID- 1913685 TI - Extracellular matrix and the patterns of differentiation of human endometrial carcinomas in vitro and in vivo. AB - Adenocarcinomas differ in their ability to form glandular structures, and the mechanism regulating this architectural differentiation is unknown. In the present study, the patterns of differentiation of two human endometrial carcinomas that differed with respect to their ability to form glands in their original host were studied in monolayer and three-dimensional cultures as well as in xenografts in athymic mice. A moderately differentiated adenocarcinoma of human endometrium, EnCa101, transplanted into nude mice formed tumors indistinguishable from the original neoplasm and secreted mucin. A cell line derived from this tumor, ECC-1, formed monolayers on tissue culture substratum and lost the ability to secrete mucin. However, upon culture within Matrigel, the ECC-1 cells formed glandular structures and secreted mucin. Ultrastructural examination revealed morphological polarity, as evident by intraluminal microvilli and characteristic adhesion structures composed of tight, gap, and desmosomal junctions adjacent to the lumen, and secretory activity. Whereas basal lamina was observed in vivo around glandular cells, epithelial cells were not tethered in vitro with this structure. In contrast, the epithelial cells of a poorly differentiated human endometrial adenocarcinoma, AN3, failed to form glands in nude mice or in Matrigel in vitro. These findings illustrate that gland forming ability is an intrinsic property of well to moderately differentiated adenocarcinoma cells and that only cells with this inherent potential can be induced to form glands in response to appropriate extracellular signals. PMID- 1913686 TI - Interleukin 4 alone and with gamma-interferon or alpha-tumor necrosis factor inhibits cell growth and modulates cell surface antigens on human renal cell carcinomas. AB - Immune cytokines have been shown to play important roles in regulating immune cell functions as well as neoplastic cells. Interleukin-4 (IL4), primarily known as a B-cell growth factor, can also activate and differentiate other immune cells. This cytokine has recently been shown to have immunotherapeutic benefit in tumor-bearing hosts. The present study assessed the effect on human renal cell carcinoma cell lines of recombinant IL4 alone and in combination with recombinant gamma-interferon (IFN) or recombinant alpha-tumor necrosis factor (TNF). IL4 inhibited cell growth of all lines at 250-500 units/ml in a differential manner. Expression of IL4 receptors was demonstrated on renal cell carcinomas. Overall, IFN (500 units/ml) alone inhibited cell growth; however, TNF (500 units/ml) was not as strong an inhibitor. When IL4 was combined with IFN or TNF there was a significant augmentation of cell growth inhibition and modulation of cell morphology of the cell lines. Tumor-associated ganglioside antigens (NeuAc alpha 2-3Gal beta 1-4Glc beta 1-1'Cer, NeuAc alpha 2-8NeuAc alpha 2-3Gal beta 1-4Glc beta 1-1'Cer, GalNAc beta 1-4 (NeuAc alpha 2-3)Gal beta 1-4Glc beta 1-1'Cer, and GalNAc beta 1-4(NeuAc alpha 2-8NeuAc alpha 2-3)Gal beta 1-4Glc beta 1-1'Cer) HLA class I, HLA-DR, and beta 2-microglobulin on the cell surface of renal cancer lines were assessed by flow cytometry and radiometric binding assay. IL4 alone or in combination with other cytokines modulated HLA class I and HLA-DR expression. IL4 and IFN consistently enhanced NeuAc alpha 2-8NeuAc alpha 2-3Gal beta 1-4Glc beta 1-1'Cer and GalNAc beta 1-4(NeuAc alpha 2-8NeuAc alpha 2-3)Gal beta 1-4Glc beta 1-1'Cer expression on individual cell lines. The study demonstrated that IL4 alone or in combination with other cytokines can significantly inhibit growth, and modulate the expression of surface major histocompatibility and tumor associated antigens of renal cell carcinomas. PMID- 1913687 TI - Identification of a novel tumor-associated Mr 110,000 gene product in human gastric carcinoma cells that is immunologically related to carcinoembryonic antigen. AB - A novel gene product which is immunologically related to carcinoembryonic antigen (CEA) and constitutively expressed by six of eight human gastric carcinoma cell lines is described. The antigen was initially identified by the differential binding patterns of four monoclonal antibodies (MAbs) which recognize the putative Mr 180,000 CEA and/or the Mr 90,000 CEA-related gene product, NCA (normal cross-reacting antigen). Western blot analyses of partially purified membrane fractions prepared from Hs 746T gastric carcinoma cells identified an Mr 110,000 antigen. Northern blot analyses using CEA- and NCA-specific complementary DNA probes did not identify any specific CEA or NCA transcripts in polyadenylate selected mRNA isolated from the Hs 746T cells. Likewise, a probe designed to hybridize with different CEA-related family members failed to identify a CEA related message in the Hs 746T cells. Subsequent studies revealed that interferon gamma (IFN-gamma) treatment substantially increased the level of expression of the Mr 110,000 antigen on the Hs 746T and five other gastric cell types that constitutively expressed the antigen. IFN-gamma treatment also de novo induced the expression of the Mr 110,000 antigen on the surface of GaCa gastric carcinoma cells. A high percentage of Hs 746T (i.e., greater than 85%) and GaCa (approximately 75%) gastric carcinoma cells expressed the Mr 110,000 antigen after IFN-gamma treatment; yet, neither cell type expressed CEA or NCA as measured by the binding of the anti-CEA MAb, COL-1, or B6.2, an anti-NCA MAb. In contrast to CEA and NCA, phosphatidylinositol phospholipase C treatment failed to release the Mr 110,000 antigen from the surface of the Hs 746T or IFN-gamma treated GaCa cells, suggesting that membrane attachment of this novel antigen is not via a glycosyl-phosphatidylinositol anchor. Finally, primers that amplify the 420 base pairs of the immunoglobulin-like domain of CEA and NCA detected an appropriately sized product in untreated as well as IFN-gamma-treated GaCa cells using the polymerase chain reaction method. Thus, a potentially novel gene product coding for an Mr 110,000 antigen that is strongly upregulated by IFN gamma has been identified in human gastric carcinoma cells. Immunologically, the antigen shares reactive epitopes with CEA and its related NCA gene product; however, Northern blot analyses, polymerase chain reaction, and phosphatidylinositol phospholipase C results suggest that the antigen may be, at best, a distant relative of the CEA gene family. PMID- 1913688 TI - Comparison of immunoscintigraphy and computerized tomography in identifying colorectal cancer: individual lesion analysis. AB - Monoclonal antibody scintigraphy with 111In-ZCE025 was used in presurgical staging of 45 patients prior to abdominal exploration for primary, recurrent or metastatic colorectal carcinoma. A total of 186 lesions were identified, of which 147 were evaluated by abdominal surgery and pathology. Sensitivity was 40.5% (49 of 121) for immunoscintigraphy (IS), 61.2% (74 of 121) for computerized tomography (CT), and 72.7% (88 of 121) for IS and CT combined. The positive predictive value was 83.1% (49 of 59) for IS and 88.1% (74 of 84) for CT. Sensitivity of IS was 100% (23 of 23) for primary tumors, 17.7% (11 of 62) for hepatic metastases, and 41.7% (15 of 36) for extrahepatic abdominal metastases. Of the 50 hepatic lesions evaluated by single-proton emission computerized tomography, 11 were localized by IS. Only one was visualized by planar scintigraphy. Sensitivity of CT was 87% (20 of 23) for primary tumors, 67.7% (42 of 62) for hepatic metastases, and 33.3% (12 of 36) for extrahepatic abdominal metastases. Sensitivity of IS combined with CT was 72.6% (45 of 62) for hepatic and 55.6% (20 of 36) for extrahepatic abdominal metastases. Of 24 malignant lesions measured by the pathologist to be less than 3.0 cm (maximum dimension), 7 (29.2%) were detected by IS and 3 (12.5%) by CT. Of 28 malignant lesions greater than 3.0 cm, 23 (82.1%) were detected by IS and 24 (85.7%) by CT. Overall, IS and CT complemented each other in presurgical staging of colorectal carcinoma. IS was of greater value for identification of extrahepatic and small metastases. CT was more effective for identification of hepatic metastases. PMID- 1913689 TI - Human malignant histiocytosis CD30+ DEL cell line differentiates into macrophage like cells when treated with a phorbol diester. AB - The histiocytic or lymphoid origin of human malignant histiocytosis is currently a subject of debate. The aim of this study was to investigate the in vitro effects of 12-O-tetradecanoylphorbol-13-acetate used as a differentiation inducer on the CD30, t(5;6)(q35;p21) DEL cell line, taken to be a reliable representative of the human malignant histiocytosis cell line. Treatment of DEL cells with 33 nM 12-O-tetradecanoylphorbol-13-acetate for 6-24 h resulted in cell surface attachment (up to 80%), decrease in dividing ability, enhancement of nitro blue tetrazolium reducing capacity (from 8 to 42%), occurrence of a limited immunodependent phagocytosis, and transient increase in expression of tumor necrosis factor alpha gene and in production of tumor necrosis factor alpha protein, whereas tumor necrosis factor beta remained undetectable. From these data, we can conclude that the malignant histiocytosis DEL cell line is not of lymphoid origin but stems from a myelomonocyte lineage. PMID- 1913690 TI - Androgen sensitivity of the new human breast cancer cell line MFM-223. AB - The mammary carcinoma cell line MFM-223 is characterized by high androgen and low estrogen and progesterone receptor levels. With the dextran charcoal method, androgen binding was determined at 160 fmol/mg protein corresponding to approximately 100,000 binding sites per cell in whole cell binding assays. The estrogen and progesterone receptor contents were between 8 and 18 fmol/mg protein. The proliferation of MFM-223 cells was significantly inhibited by doses greater than 0.01 nM dihydrotestosterone. The androgenic inhibition of cell proliferation was antagonized by the antiandrogens cyproterone acetate and hydroxyflutamide. In spite of the low estrogen receptor content, MFM-223 cell proliferation was slightly enhanced by 10 nM 17 beta-estradiol. Treatment with 17 beta-estradiol or dihydrotestosterone failed to provoke an increase of the progesterone receptor level. MFM-223 cells have characteristic patterns of isoenzyme polymorphism and of karyotype alterations revealing marker chromosomes and homogeneously staining regions. In the spectrum of human mammary carcinoma cell lines, MFM-223 cells offer a unique model to investigate molecular mechanisms of androgen receptor action. PMID- 1913691 TI - Human colonic sulfomucin identified by a specific monoclonal antibody. AB - Since the 1960s, the loss of sulfomucin from colonic epithelium has been considered to be an indicator of an early stage of carcinogenesis; yet, the biochemical basis for this phenomenon has never been elucidated. We recently prepared a monoclonal antibody (mAb) 91.9H that immunoprecipitates the normal colonic mucins metabolically incorporating [35S]-sulfate. This mouse IgG1 antibody did not cross-react with colon carcinoma mucins that lack sulfate groups. Using normal colonic epithelia unlabeled or radiolabeled with [35S]sulfate and [3H]glucosamine, we purified a high molecular weight glycoprotein that reacts with mAb 91.9H. This was achieved by a combination of DEAE-cellulose anion-exchange chromatography, consecutive treatments with chondroitinase ABC plus heparitinase and with sodium dodecyl sulfate plus 2 mercaptoethanol, and gel filtration on Sepharose CL-2B in the presence of 8 M urea. Antibody reactivity was found in acidic but not neutral high molecular weight glycoproteins. After Sepharose CL-2B fractionation, the mAb 91.9H-reactive fractions consisted of a component with an approximate molecular weight of 500,000-900,000. A purified sulfomucin contained protein, neutral sugar, amino sugar, sialic acid, and sulfate in an approximate ratio of 2.5:1.0:1.1:0.4:0.5. The polypeptide portion was rich in hydrophilic amino acids, particularly threonine. Binding of mAb 91.9H in solid-phase assays was inhibited to 50% by purified normal colon acidic mucin at doses of 5-50 micrograms/ml, depending on different preparations. Various glycosaminoglycans or sulfatides did not show inhibitory activity. Sulfomucin reactivity with mAb 91.9H, as determined by solid phase-binding inhibition and by dot blot assays, was significantly reduced by chemical desulfation of sulfomucins with anhydrous hydrochloric acid, suggesting that sulfate groups served as a portion of the immunochemical determinant for this antibody. Sulfate residues were apparently linked to alkaline-sensitive carbohydrate chains, but alkaline-released carbohydrate chains did not react with mAb 91.9H. Immunohistochemical examinations showed that mAb 91.9H bound normal colonic epithelial cells, which also stained with high-iron diamine, more strongly than it bound colon carcinoma cells. PMID- 1913692 TI - Inactivation of the retinoblastoma gene in human bladder and renal cell carcinomas. AB - The retinoblastoma (RB) gene was the first tumor suppressor gene isolated and its inactivation is associated with the pathogenesis of several types of human cancer. In this study, we investigated the involvement of the RB gene in bladder and renal cell carcinomas by determining the loss of heterozygosity (LOH) at the RB locus and by DNA, RNA, and protein analysis of the RB gene. Whenever possible, the latter included Western blotting and immunohistochemical staining of the RB protein. In bladder carcinoma, 2 of the 8 cell lines we studied had an inactivated RB gene; one cell line lacked RB expression without a gross RB deletion, whereas the other cell line expressed only the underphosphorylated form of the RB protein. None of 16 low-grade noninvasive bladder carcinomas showed an alteration in RB protein by direct Western blot analysis, whereas 2 of 14 high grade, invasive tumors had no RB protein as measured by both Western blotting and immunohistochemical staining. This suggests that the loss of RB function may be more important in the progression of bladder cancer than in its initiation, although more extensive studies are required. LOH within the RB locus was observed in 5 of 27 informative cases of primary bladder, ureter, or renal pelvis carcinoma. However, none of the 5 cases with LOH at the RB locus had a functional loss of RB protein expression. In renal cell carcinoma, one of the 12 cell lines had a gross homozygous deletion of the RB gene, and 2 of 32 primary tumors were negative for RB protein expression. LOH at the RB locus also was found in only 2 of 30 informative cases, one of which lacked RB expression. These results are the first to demonstrate the involvement of RB inactivation in the development of advanced primary bladder carcinoma and suggest that RB loss could have a role in certain renal cell carcinomas. Our data, however, show no correlation between LOH at the RB locus in bladder cancer and actual inactivation of the RB gene at the protein level. This may suggest that there is a second tumor suppressor or recessive cancer gene on chromosome 13 in bladder cancer and/or that the mechanism of RB inactivation in bladder cancer frequently involves independent mutations of each RB allele. PMID- 1913693 TI - Immunohistochemical and pharmacokinetic characterization of site-specific immunoconjugate 15A8-glycyl-tyrosyl-(N-epsilon-diethylenetriamine pentaacetic acid)-lysine derived from anti-breast carcinoma monoclonal antibody 15A8. AB - In this study, the breast carcinoma-reactive monoclonal antibody 15A8 and a site specific immunoconjugate of the antibody, 15A8-glycyl-tyrosyl-(N-epsilon diethylenetriamine pentaacetic acid)-lysine (15A8-GYK-DTPA), were characterized by immunohistological methods for reactivity with normal and neoplastic human tissues and normal cynomolgus monkey tissues. In addition, 15A8-GYK-DTPA labeled with 111In was assessed by in vivo imaging and pharmacokinetic studies for localization to human tumor xenografts in nude mice. The native antibody and the site-specific immunoconjugate exhibited similar limited reactivity with normal human tissues. Specifically, epithelial structures, including normal breast epithelium, lung alveoli, bronchial epithelium and glands, liver bile ducts, pancreatic ducts, kidney distal and collecting tubules, epidermal and esophageal epithelium, endometrial glands, and thymic Hassall's corpuscles, were reactive. Normal monkey tissues stained with 15A8 exhibited a similar pattern of reactivities. Antibody 15A8 reacted broadly with epithelium-derived tumors; more than 60% of the cells in all of the breast, colon, non-small cell lung, ovarian, prostate, bladder, and renal carcinomas tested expressed the antigen. In contrast, a variety of nonepithelial neoplasms, including lymphomas, melanomas, sarcomas, and small cell lung carcinomas, were nonreactive. 15A8-GYK-DTPA-111In administered i.v. rapidly localized to and imaged both MX-1 and MCF-7 human breast carcinoma xenografts in nude mice, reaching maximal levels of about 20% of injected dose/g of tumor within 4 days. No unusual localization to any nontumor tissue or organ was seen; the level of radioactivity in the normal tissues and organs was at or below that seen in the blood. Furthermore, the immunoconjugate did not accumulate in xenografts of the antigen-negative breast carcinoma ZR-75 1, which indicates that tumor localization was antigen specific. Pharmacokinetic studies in cynomolgus monkeys suggested that significant amounts of 15A8-GYK-DTPA 111In did not localize to normal epithelia and demonstrated that the immunoconjugate was not toxic. These findings suggest that antibody 15A8 may be useful in the diagnosis and therapy of breast cancer and possibly other carcinomas. PMID- 1913695 TI - pH dependence of 5-fluorouracil uptake observed by in vivo 31P and 19F nuclear magnetic resonance spectroscopy. AB - Multinuclear nuclear magnetic resonance spectroscopy was used to follow the metabolism and kinetics of 5-fluorouracil (5FU) after i.v. administration at a dose of 100 mg/kg on Wistar rats. 31P spectra allow one to determine both the energetic status and the pH of the tissues under investigation, while serial 19F spectra reveal the drug clearance. Analyses of 5FU kinetics show that the half life of 5FU elimination is about 35 min in tissue with a pH of 7.3. However, this half-life increases 2.5-fold when the local pH decreases below 6.9. Thus, acidification seems to induce a local retention of 5FU, which tends to prove the existence of active transport. This retention of the drug may have significant clinical implications for assessing and improving chemotherapy alone or in combination. PMID- 1913694 TI - Frequent loss of heterozygosity at the retinoblastoma locus in human esophageal cancers. AB - Abnormalities in the retinoblastoma tumor suppressor gene (Rb) have been observed in a large number of human cancers. Loss of heterozygosity is a common mode of allelic inactivation of Rb and other tumor suppressor genes. We investigated DNA from 61 primary human esophageal tumors for loss of heterozygosity at the Rb locus using a polymerase chain reaction-based restriction fragment length polymorphism assay. Of informative cases, we found loss of heterozygosity in 14 of 26 (54%) squamous cell carcinomas and 5 of 14 (36%) adenocarcinomas. These data support the hypothesis that Rb inactivation is involved in the pathogenesis and/or progression of esophageal cancer. PMID- 1913696 TI - Induction of immunogenicity of monoclonal antibodies by conjugation with drugs. AB - Human anti-mouse antibody has been a nearly consistent result of human clinical trials utilizing murine antibodies. It is generally anticipated that the problem of human anti-mouse antibody will be reduced as genetically engineered, more human ("humanized") antibodies become available. It is not clear, however, what effect chemical modification of such "humanized" antibodies will have on their immunogenicity. The present studies utilize a mouse antibody and rat host model to explore aspects of this question. Rats injected with unmodified mouse monoclonal antibodies failed to mount anti-mouse immune responses, presumably due to their phylogenetic relatedness. In contrast, rats injected with a Vinca immunoconjugate mounted strong anticonjugate antibody responses that were directed primarily against the linker portion of the conjugate. The in vivo serum pharmacokinetics of 125I-labeled antibody and conjugates were evaluated in rats with existing anticonjugate antibody. The peak serum level attained was inversely correlated with the level of reactivity of the anticonjugate antibody with the injected compound. This model provides a potentially useful tool for exploration of the immunogenicity of drug, toxin, or radionuclide monoclonal antibody conjugates. PMID- 1913697 TI - The treatment of orthostatic hypotension with dihydroxyphenylserine. AB - Neurogenic orthostatic hypotension is an incapacitating symptom of central and peripheral autonomic nervous system degeneration. It occurs in such clinical conditions as multiple system atrophy, pure autonomic failure, and small-fiber peripheral neuropathies. Although many treatments are available, their effects are inconsistent, unsustained, and complicated by side effects. 3,4 Dihydroxyphenylserine is a synthetic, unnatural amino acid that is an immediate norepinephrine precursor. There is theoretical and clinical evidence supporting the use of this agent in the treatment of neurogenic orthostatic hypotension in patients with peripheral and central autonomic nervous system dysfunction. We review the biochemistry, pharmacokinetics, and possible mechanisms of action and clinical utility of this agent in the treatment of neurogenic orthostatic hypotension. PMID- 1913698 TI - Characterisation of the in vivo behaviour of a controlled-release formulation of levodopa (Sinemet CR). AB - The gastrointestinal transit and systemic absorption of Sinemet CR (50-200) controlled-release tablets and standard Sinemet (25-100) immediate-release (IR) tablets have been studied in fasted and fed healthy human subjects. Both formulations were labelled with a gamma-emitting radionuclide and their gastric emptying, colon arrival and in vivo disintegration profiles monitored using gamma scintigraphy. The IR dosage forms were found to disperse soon after administration and to empty rapidly from both fasted and fed stomachs. Erosion of the CR system was independent of food or stomach pH. The CR tablet was observed to disintegrate fully in the gastrointestinal (GI) tract, resulting in complete release of levodopa over a 3-4 h time period. Considerable intersubject variation was found to exist for levodopa absorption. Absorption was more protracted with Sinemet CR than with standard Sinemet, due to the controlled release characteristics of the tablet matrix. There was no rapid initial absorption phase and instead, a gradual build-up in the absorption profile occurred. PMID- 1913700 TI - Reduction of circulating 3-O-methyldopa by inhibition of catechol-O methyltransferase with OR-611 and OR-462 in cynomolgus monkeys: implications for the treatment of Parkinson's disease. AB - We studied the effectiveness of OR-611 and OR-462, two novel inhibitors of the enzyme catechol-O-methyltransferase (COMT), on 3-O-methyldopa (OMD) formation in cynomolgus monkeys following intravenous levodopa administration. OR-611 dose dependently reduced the area under the OMD concentration-vs-time curve, reduced maximum plasma OMD concentrations, delayed the time to peak OMD levels, reduced systemic levodopa clearance, and prolonged the elimination half-life of levodopa. Similar effects on peripheral levodopa metabolism were seen with doses of 15 mg/kg of OR-611 and OR-462, its sister compound, which lacks the ability to penetrate the central nervous system (CNS). PMID- 1913699 TI - Effect of MK-458 (HPMC) in Parkinson's disease previously untreated with dopaminergic drugs. A double-blind, placebo-controlled multicenter study. AB - Ninety-four patients with early Parkinson's disease were investigated in a double blind, placebo-controlled evaluation of MK-458 [hydroxypropyl methylcellulose/lactose matrix (HPMC)], a sustained release formulation of a novel naphthoxazine compound with selective D-2 dopamine receptor agonism. Patients were previously untreated with dopaminergic drugs. Efficacy was assessed by clinical rating scales and by patient self-evaluation. MK-458 (HPMC) caused a significant decrease in most parkinsonian symptoms. Though disability rating scores were lowered by the drug, the scores did not differ significantly from placebo. However, statistically significant improvement occurred with MK-458 (HPMC) on both the physician and the patient global assessments. Adverse reactions such as nausea and vomiting, sedation, confusion, and hallucinations occurred more with MK-458 (HPMC) than with placebo. MK-458 (HPMC) possesses antiparkinsonian efficacy in early Parkinson's disease; however, side-effects are frequently associated with its use. Selective D-2 receptor agonists, such as MK 458 (HPMC), may not be the ideal treatment as monotherapy for Parkinson's disease. PMID- 1913701 TI - Clinical effects of daily methamphetamine administration. AB - This study investigated alterations in the disposition and pharmacodynamics of methamphetamine HCl after daily administration. Six male paid volunteers familiar with the use of amphetamines participated. Each subject was administered 10 mg of methamphetamine HCl as a slow-release preparation (Desoxyn Gradumets) at 9 a.m. for 13 consecutive days (days 2-14 of the study). On days 1 and 15 the subjects were challenged with 10 mg of oral deuterated methamphetamine HCl. Deuterated drug was used to differentiate plasma concentrations of challenge doses from those of daily doses. The heart rate, subjective perception of "high," and plasma concentrations of methamphetamine were examined on days 1 and 15. Repeated ANOVA measures indicate that a significant decrease in heart-rate acceleration in response to methamphetamine challenge occurred on day 15 [F(1,5) = 8.26, p less than or equal to 0.035]. However, no significant change in either the subjective ratings of "high" or the plasma concentrations of deuterated methamphetamine occurred. These findings indicate that the disposition of methamphetamine and its subjective effects were not altered by this period of daily exposure to a low dose of the drug. In contrast, tolerance to the heart-rate accelerating effect was observed. PMID- 1913702 TI - Effect of clonidine and atropine on rest tremor in the MPTP monkey model of parkinsonism. AB - The purported alpha 2-adrenergic agonist clonidine was found to inhibit rest tremor at doses of 0.023-0.1 mg/kg in the 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine monkey model of parkinsonism. The effect was dose dependent, but sedation and reduced mobility were observed. Atropine at doses of 0.1-1 mg/kg also reduced tremor in a dose-dependent fashion, but side-effects in the form of agitation, dilated pupils, and dry mouth were seen. When the two drugs were combined, however, we saw a significant potentiation of the antitremor effect. We could even abolish tremor with doses of atropine and clonidine that by themselves were without effect. The side-effects were almost eliminated by the combination. PMID- 1913704 TI - Future directions for drug development for the treatment of Alzheimer's disease. Hershey, Pennsylvania, October 25, 1989. PMID- 1913703 TI - Dopa-responsive dystonia masquerading as idiopathic kyphoscoliosis. AB - A 19-year-old girl with a long-standing history of kyphoscoliosis misdiagnosed as idiopathic was offered corrective surgery on several occasions but fortunately refused, since neurological examination later found evidence of mild dystonic posturing in the neck and right leg. Symptoms worsened toward evening but improved with rest. Treatment with low doses of levodopa led to total remission within a month. Our case illustrates that dopa-responsive dystonia can manifest spinal curvature as the major symptom and warrants its inclusion in the differential diagnoses of idiopathic kyphoscoliosis. PMID- 1913705 TI - Pharmacological alleviation of combined cholinergic/noradrenergic lesion-induced memory deficits in rats. AB - Data derived from a number of preclinical studies examining the effects of combined cholinergic and noradrenergic lesions in a rat model of Alzheimer's disease are reviewed. Results from these studies indicated that a nucleus basalis of Meynert (nbM) lesion combined with a lesion of the ascending noradrenergic bundle (ANB) did not exacerbate 72-h passive avoidance retention deficits beyond the degree of impairment produced by nbM lesions alone. However, the addition of an ANB lesion did block the efficacy of two choiinomimetics (physostigmine and oxotremorine) to reverse the lesion-induced memory impairment. Memory in combined lesioned rats was restored when cholinomimetic therapy was administered in combination with low doses of clonidine. Studies investigating a number of Hoechst-Roussel Pharmaceuticals compounds have produced memory-enhancing effects in animals prepared with combined nbM/ANB lesions without the need for clonidine supplementation. These compounds include P128, P86-7493, and P87-8184. Moreover, these compounds have also been shown to be effective in reversing passive avoidance memory deficits in animals with nbM lesions and treated with the noradrenergic toxin DSP-4. Implications for pharmacotherapeutic approaches for the treatment of Alzheimer's disease are discussed. PMID- 1913706 TI - Expression of the Alzheimer amyloid precursor in brain tissue and effects of NGF and EGF on its metabolism. AB - Alzheimer's disease (AD) is the major cause of serious dementia and memory loss in several million elderly Americans. The most prominent lesions in the brains of these patients are the depositions of two types of abnormal filaments: the predominantly intraneuronal neurofibrillary tangles (NFT), which consist of paired helical filaments (PHF), and the extracellular amyloid fibers. These changes are characteristic of AD, and a final diagnosis of this disease is based on the presence of large numbers of these abnormal filamentous structures in the patient's brain. The amyloid fibers consist of a peptide subunit termed beta protein or A4 peptide, which derives from a larger precursor protein. In this study we review the structural characteristics, regulation of expression, and metabolism of the Alzheimer amyloid precursor in brain tissue and cell cultures. PMID- 1913707 TI - Therapy for Alzheimer's disease: choosing a target. AB - There are two levels on which therapy for patients with Alzheimer's disease (AD) can be approached. The first concerns attempts to develop drugs to alleviate the symptoms of the disease. Almost all of the ongoing drug trials fit into this category. The second level of treatments will be designed to alter the rate of progression of the disease, and perhaps even try to reverse some of the molecular and structural abnormalities. At neither level is it clear that we can identify the key features of AD that should be the prime target of therapeutic strategies. This article will review the major biochemical abnormalities reported to occur in patients with AD, and the relative merits of targeting drug development research to these. PMID- 1913708 TI - Cerebral blood flow and metabolism in aging and dementia. AB - There are structural, perfusive, and metabolic changes that occur in normal aging and in dementia. In Alzheimer's disease (AD), changes in blood flow and metabolism occur primarily in the parietal and temporal cortices. These changes are distinct from those seen in normal aging. These alterations correspond to known neuronal changes that occur in AD and are consonant with changes that are seen in cognitive function. Characteristic patterns are also emerging in other forms of dementia such as Pick's disease, multi-infarct dementia, and primary progressive aphasia. Finally, there is some preliminary evidence that functional neuroimaging procedures may be useful in both the diagnosis and treatment strategies of dementia. PMID- 1913709 TI - The nicotinic receptor genes. AB - The causative factor(s) of Alzheimer's disease (AD) are presently unknown. However, it has been shown that the number as well as the fraction of high- to low-affinity nicotine binding sites is altered in patients suffering from this disease. This finding, along with the identification of seven genes which code for nicotinic receptors expressed in the mammalian brain, has led to the idea that one nicotinic receptor subtype may be specifically altered in AD. The present article reviews how, through a molecular genetic approach, a family of genes coding for nicotinic acetylcholine receptor subtypes was uncovered. Also discussed is the use of in situ hybridization to determine the distribution of expression of the mRNA encoding for each receptor subtype and the patch clamp technique to characterize their biophysical properties. Determination of the promoters of these genes, as well as the properties of the expressed receptor subtypes, may make it possible to design new specific nicotinic receptor subtype drugs that will treat not only the symptoms of AD but the progression of the disease process as well. PMID- 1913710 TI - Nerve growth factor and Alzheimer's disease. AB - Clinical trials with cholinergic agents suggest that cholinergic hypertrophy may be beneficial in the treatment of Alzheimer's disease (AD). Recent findings substantiate the view that nerve growth factor (NGF) selectively acts on cholinergic neurons. In adult rats and primates, intraventricular administration of nerve growth factor produces trophic actions on cholinergic neurons and prevents age related neuronal atrophy. These findings suggest the possibility of the eventual development of pharmacological applications of nerve growth factor for the treatment of AD. PMID- 1913711 TI - Amyloid-related proteins and nerve growth factor in Alzheimer's disease and animal models. AB - Alzheimer's disease (AD), the most common cause of dementia in adult life, is characterized by the deposition of amyloid in brain parenchyma and the degeneration of specific populations of nerve cells, including cholinergic neurons in the basal forebrain. In this review, we first outline studies of cellular and molecular events that lead to age-associated deposition of amyloid in the brains of nonhuman primates and then describe investigations of the effect of treatment with nerve growth factor (NGF) on experimentally induced abnormalities in cholinergic neurons of the basal forebrain. These studies of amyloidogenesis and the efficacy of trophic factors on specific groups of experimentally damaged neurons provide information about issues central to understanding the pathogenesis and treatment of human degenerative diseases, including AD. PMID- 1913712 TI - [Efficacious changes in blood volume: interactions between circulation components and water-electrolyte metabolism]. PMID- 1913713 TI - [Hemodynamic response to somatostatin at rest and during sympathetic activation in idiopathic orthostatic hypotension]. AB - Idiopathic orthostatic hypotension (IOH) represents a degenerative disorder of the peripheral nervous system characterized by low values of arterial blood pressure during orthostatism, with reduction in serum catecholamines. Since treatment of symptomatic IOH has been unsatisfactory till now, we studied the hemodynamic response to somatostatin (S) (Octreotide, 100 micrograms sc) at rest (R) and during sympathetic activation (tilting, T) by means of 2D and/or color Doppler echocardiography, in 5 ambulatory IOH patients (4M, 1F; aged 65 +/- 5 years), with simultaneous recording of blood pressure and heart rate. Post-S, an increased blood pressure was evident during T without heart rate modifications (pre- vs post-S, SAP: 92 +/- 9 vs 148 +/- 12; DAP: 61 +/- 4 vs 90 +/- 9 mmHg; p less than 0.05), while systolic echo parameters did not change significantly. Doppler aortic velocity curve showed during T a reduction of Vmax (pre- vs post S: 0.98 +/- 0.09 vs 0.73 +/- 0.03 m/s; p less than 0.05) and of cardiac output, due to unchanged preload. Pre-S, at rest, Doppler mitral velocity curve presented a normal E/A ratio as in normal subjects, with a reduced E peak and an increased A peak post-S, indirect signs of increased afterload. Pre-S, E and A peak velocities underwent progressive decrease during T, markedly more evident post-S. Total peripheral resistance, at rest and during T, increased post-S too (pre- vs post-S, rest: 2406 +/- 267 vs 3162 +/- 599; T: 1634 +/- 201 vs 2784 +/- 425 dyne*s/cm-5; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1913715 TI - Myocardial perfusion in Friedreich's ataxia: assessment by dipyridamole thallium 201 imaging. AB - In order to assess myocardial perfusion in patients with Friedreich's ataxia, we carried out dipyridamole-thallium imaging in 13 cardiologically asymptomatic patients (aged 16 to 39; mean age 24) with various degrees of left ventricular hypertrophy; all showed electrocardiographic ST and/or T wave abnormalities before scintigraphy. After dosing with dipyridamole-201 thallium, we found: a completely reversible perfusion defect in the apical and a partially reversible defect in the posterolateral wall of the left ventricle in 1 case; a partially reversible perfusion defect in the anterior and posterior walls of the left ventricle in 1 case; and a persistent anterolateral perfusion defect in 1 case. The remaining 10 patients showed no scintigraphic abnormalities. The fact that only 1 of our patients showed a completely reversible perfusion defect, possibly consistent with regional myocardial ischemia, suggests that ischemia does not play a major role in the pathogenesis of the cardiac involvement in Friedreich's ataxia. PMID- 1913714 TI - Role of endogenous opioids on nociceptive threshold in patients with exercise induced myocardial ischemia. AB - To evaluate whether endogenous opioids (EO) play a role in the perception of anginal pain, a randomized double blind clinical trial, using naloxone (N) and placebo (P) and measuring beta-endorphin (beta-ep) plasma levels, was performed. We studied 10 patients with angiographically assessed coronary artery disease (CAD) and stable exercise-induced myocardial ischemia (established by 2 preliminary bicycle ergometric tests) of whom 5 symptomatic (SYM) and 5 asymptomatic (ASYM) and 5 subjects without CAD as a control group (CON). On a third exercise test the beta-ep plasma level (fmol/ml) was measured at rest (SYM 5.4 +/- 2.3 vs ASYM 7.2 +/- 2.3 vs CON 6.8 +/- 2.6, NS), at peak exercise (SYM 4.4 +/- 1.8 vs ASYM 8.0 +/- 4.2 and vs CON 6.2 +/- 2.7, NS) and during recovery (SYM 7.5 +/- 4.2 vs ASYM 7.2 +/- 3.0 vs CON 6.7 +/- 2.5, NS). On 2 subsequent tests patients received N (0.2 mg/kg) or P intravenously and chest pain was evaluated on an analogue scale (score from 1 to 10). After N compared to P we observed: an increased perception of chest pain in SYM (6.8 +/- 1.5 vs 4.2 +/- 1.0; p less than 0.01) without significant changes of the ischemic threshold (total work, heart rate-blood pressure product, ST segment changes, 2D echocardiographic wall motion abnormalities); no modifications in ASYM and CON.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1913716 TI - [Role of transesophageal echocardiography in the diagnosis of diseases of the thoracic aorta]. AB - The most frequent diseases of thoracic aorta in the adult population, aneurysms and dissection, can lead to dramatic complications. Therefore in these cases an early and careful diagnosis is required for a correct therapeutic choice. The close distance of the thoracic aorta to the esophagus allows a better visualization by transesophageal echocardiography (TEE) compared with the transthoracic approach (TTE). Aim of this study is to evaluate the diagnostic accuracy of TEE versus surgical data in patients with suspected aneurysms and/or dissection of the thoracic aorta. Eighteen patients with aortic aneurysm, confirmed at surgery, underwent B-mode, pulsed Doppler and color echocardiographic examination either by TTE or by TEE. TEE was concordant with surgical findings in all the cases of fusiform (8 patients) and saccular (2 patients) aneurysms, visualizing aortic wall thrombosis in 4 patients. Furthermore TEE, diagnosed all the type I (4 patients) and type III (2 patients) dissection, and 1 type II, identifying in all cases the intimal tear and, in 3 patients, the false lumen thrombosis; it demonstrated the presence of severe aortic regurgitation in 3 patients and of mild pericardial effusion in 2 patients. Only in 1 case of type II dissection TEE was not diagnostic because it is not able to visualize completely the aortic arch. In our experience TEE allowed accurate information in patients with aortic aneurysm or dissection. TEE can be considered the first choice diagnostic tool in patients with suspected dissection of the thoracic aorta. PMID- 1913717 TI - [Variations in arrhythmogenic response to catecholamines in acute myocardial ischemia]. AB - Several studies have demonstrated that focal mechanisms contribute to arrhythmogenesis during acute myocardial ischemia in vivo. However, the biochemical derangements during ischemia may either potentiate or depress the electrophysiological mechanisms leading to focal arrhythmias. In the study presented here we have characterized the consequences of various levels of cellular depression and of alterations in the extracellular environment on the development of early (EADs) and delayed (DADs) afterdepolarizations induced by catecholamines. Adult canine myocytes were exposed to: normoxia; hypoxia (pO2 less than 10 mmHg); hypoxia + high K+ or cyanide infusion. Early and delayed afterdepolarizations were induced by alpha or beta adrenergic stimulation in the different experimental conditions by infusing isoproterenol (10(-8)-10(-6) M) or phenylephrine (10(-7)-10(-5) M) + the betablocker nadolol. Hypoxia did not modify EADs or DADs induced by beta stimulation and potentiated DADs induced by alpha stimulation; hypoxia + high K+ blunted DADs induced by both types of stimulation and cyanide infusion completely prevented and suppressed them. Thus, triggered arrhythmias dependent upon adrenergic stimulation can either be potentiated or inhibited by the biochemical derangements of acute ischemia. Focal arrhythmias are more likely to occur in the borderline ischemic cells where cellular depression and extracellular K+ accumulation are less marked. PMID- 1913719 TI - [Prosthetic valve endocarditis caused by Gemella haemolysans]. AB - Reported herein is the case of a 47 year old man with mitral and aortic bioprosthetic valves who developed endocarditis. Blood cultures turned out to be positive for Gemella haemolysans, a commensal of the upper respiratory tract. Proper antibiotic therapy was immediately started according to antibiogram, and continued after the acute stage of the disease had been overcome. The aortic prosthesis appeared much more to be incompetent at Doppler and aortography (from 2/4 to 3/4). At surgery, the gross appearance of the explanted xenograft was consistent with infective endocarditis. The case is described for the rarity of the etiology: only 6 cases of infective endocarditis from Gemella haemolysans are reported in the literature, but this is the first involving a prosthetic valve. PMID- 1913718 TI - [Toxicity of fatty acids during myocardial reperfusion: a new possible mechanism of action]. AB - To assess the value of myocardial substrate in the occurrence of ischemic reperfusion damage, isolated, electrically paced rabbit hearts were perfused for 60 min under aerobic condition (25 ml/min with oxygenated Krebs-Henseleit solution containing glucose 11 mM). Thereafter the hearts were made ischemic for 30 min by reducing coronary flow to 3 ml/min. During ischemia, 3 different substrates were used glucose 11 mM (Group I), palmitate 1.2 mM (Group II) and palmitate 1.2 mM + glucose 11 mM (Group III). The hearts were then reperfused (25 ml/min) for 30 min under aerobic condition using glucose 11 mM as the only substrate. In the presence of glucose with or without palmitate (Group I and III) ischemic damage was mild. Recovery of the developed pressure was 95% and there was no contracture during ischemia and or reperfusion. During ischemia and reperfusion there was a small release of CPK, GSSG and GSH. In the presence of palmitate (Group II) ischemic and reperfusion damage was profound. Recovery of developed pressure was reduced (25%) and diastolic pressure significantly increased (68 +/- 5.1 vs 3 +/- 1.5, 5 +/- 1.8 mmHg). These mechanical data were concomitant with an important release of CPK (580 +/- 50 vs 180 +/- 35, 210 +/- 48 mU/min/gww) and oxidised glutathione (0.38 +/- 0.3 vs 0.05 +/- 0.001, 0.09 +/- 0.003 nmoles/min/gww). In addition the redox state of the cells of the Group II was significantly shifted through the oxidative state at the end of ischemia and of reperfusion. These results indicate that palmitate as substrate increases the deleterious effects of ischemia; glucose is able to overcome the negative effects of palmitate. PMID- 1913720 TI - [Neural control of hemodynamic changes in physical exercise during physiological conditions]. PMID- 1913721 TI - Functional and structural effects of ACE inhibitors on the cardiovascular system. AB - There is considerable interest in the ability of angiotensin-converting enzyme (ACE) inhibitors not only to lower blood pressure, but also to reverse hypertension-induced remodelling of the circulation. Recently published data would suggest that treatment of spontaneously hypertensive rats from an early age with ACE inhibitors will prevent the development of the expected changes in the resistance vessels as the animals age and that withdrawal of treatment is followed by a lag period before the blood pressure rises. Such findings appear to be contrary to those obtained with other hypertensive drugs where morphological changes are not as effectively attenuated and blood pressure rises rapidly after withdrawal of treatment. There is some evidence for a relationship between the efficacy of ACE inhibitors in this area and lipid solubility. This raises the possibility that the mechanism at work is related to the inhibition of tissue located renin-angiotensin systems both in vascular smooth muscle and elsewhere, possibly in the central nervous system. An overall review of the literature indicates that treatment of spontaneously hypertensive rats with ACE inhibitors can result in prolonged reduction of blood pressure, even after treatment is withdrawn. Comparisons with other treatments suggest that it is easier to reduce blood pressure than to reverse vascular structure. However, achieving a reversal in morphological changes in resistance vessels as well as controlling blood pressure may be important for reducing the mortality from ischaemic heart disease. ACE inhibitors may have a direct effect on reversal of vascular structure, but other sites of action may also be important in this aspect of their action. PMID- 1913722 TI - Angiotensin II receptor subtypes in rat brain and peripheral tissues. AB - Angiotensin II (Ang II) receptor binding was localized in rat adrenal gland, kidney, and brain by in vitro autoradiography using the antagonist analogue 125I [Sar1, Ile8]Ang II and differentiated into type I (AT-1) and type II (AT-2) subtypes using unlabelled non-peptide antagonists specific for Ang II subtypes. AT-1 binding was determined as that remaining in the presence of an excess of the AT-2 antagonist, PD 123177 (10 microM), and AT-2 binding as that remaining in the presence of an excess of the AT-1 antagonist, DUP753 (10 microM). The reducing agent dithiothreitol decreased the binding to AT-1 receptors and enhanced the binding to AT-2 receptors. The rat adrenal gland contains both AT-1 and AT-2 receptors in the ratio of approximately 3:2 in the cortex and 1:9 in the medulla. By contrast, in the kidney only AT-1 receptors were evident in glomeruli, proximal tubule, and inner stripe of the outer medulla. In the brain, the pattern of Ang II receptor subtypes varies greatly from region to region. Many brain structures known to be involved in blood pressure regulation and fluid and electrolyte balance, such as circumventricular organs (including vascular organ of the lamina terminalis, subfornical organ, median eminence, and area postrema), median preoptic nucleus, hypothalamic paraventricular nucleus, and regions in the medulla oblongata involved in autonomic control (nucleus of the solitary tract, dorsal motor nucleus of the vagus, and intermediate reticular nucleus), contain exclusively AT-1 receptors. By contrast, locus coeruleus, lateral septal nuclei, superior colliculus, subthalamic nucleus, many nuclei of the thalamus, and nuclei of the inferior olive contain predominantly AT-2 receptors. The detailed binding characteristics of each subtype were determined by competition studies with a series of antagonists. The pharmacological specificity obtained in kidney, adrenal cortex and adrenal medulla, superior colliculus, and nucleus of the solitary tract produces specificity patterns which confirm the assignments of AT 1 and AT-2 receptors described above. The present study reveals important pharmacological heterogeneity of Ang II receptors in key target organs. The subtype-specific receptor mapping described here is relevant to the understanding of the role of angiotensin peptides in peripheral organs and in the central nervous system and is relevant to the actions of non-peptide Ang II receptor antagonists. PMID- 1913723 TI - Clinical evaluation of the peripheral vasculature. AB - Cardiologists are becoming more interested in peripheral arterial disease with the development of sophisticated noninvasive diagnostic techniques and invasive therapeutic modalities for the symptomatic patient. The clinical diagnosis of occlusive arterial disease, which is predominantly atherosclerosis, is relatively easy and a clue to the possibility of coexistent underlying coronary disease or cerebrovascular disease or both. Occlusive arterial disease of the lower extremities is more prevalent in men than in women. Nevertheless, the lifestyle of women is increasingly similar to that of men, especially with regard to smoking and diet. Therefore, the role of primary prevention remains the cornerstone of treatment. PMID- 1913724 TI - Peripheral vascular disease in the elderly. PMID- 1913725 TI - Use of noninvasive vascular laboratory in diagnosis of venous and arterial disease. AB - The development and widespread availability of noninvasive testing have revolutionized the approach to the diagnosis of vascular disease. Noninvasive tests are safe, can be performed on an outpatient basis, and are readily repeatable. These tests require skill and experience to perform with acceptable accuracy. In experienced hands, they compare favorably with standard angiography, and, after the initial cost, are less expensive. B-mode ultrasonography provides a gray scale image of the blood vessels. Doppler probes permit analysis of flow patterns and velocity. Color flow imaging, the latest advance, combines high resolution B-mode and Doppler imaging systems using a computer to provide simultaneous anatomic and physiologic information. This method is a faster and more accurate means of detecting and evaluating the extent of vascular disease. Noninvasive testing is useful in assessing the carotid arteries before vascular or other high-risk operation. Stratification of the risk of future stroke is possible with these tests. This stratification assists in the selection of candidates for carotid surgery among patients with symptomatic carotid disease or asymptomatic bruits in the neck. The hemodynamic significance of obstructive disease in the peripheral arteries can be evaluated and followed by serial noninvasive testing. Noninvasive testing is also of proven value in the surveillance of patients with arterial bypass grafts and in diagnosing local vascular complications of arterial catheterization. Acute and recurrent deep venous thrombosis can be diagnosed accurately by noninvasive testing, greatly reducing the need for venography. In addition, noninvasive testing is particularly suited for screening patients at high risk for developing deep venous thrombosis. PMID- 1913726 TI - The swollen leg. Clinical significance and differential diagnosis. AB - An elderly patient with a swollen leg or legs can present a challenging problem in differential diagnosis. Although most swollen legs are the result of congestive heart failure, thrombophlebitis, cellulitis, or lymphedema, many other conditions should also be considered. PMID- 1913727 TI - Pulmonary embolism in the elderly. AB - The risk of pulmonary embolism increases with age. Risk factors in the elderly include stasis caused by immobility and reduced venous tone, the increasing need for operative procedures, particularly orthopedic procedures to hip and knee, and reduced fibrinolytic activity in leg veins. The diagnosis of pulmonary embolism is difficult and is made on the basis of clinical probability, lung scan findings, investigations for deep venous thrombosis and, when indicated, by pulmonary angiography. Effective prophylactic and therapeutic approaches are now available. PMID- 1913728 TI - Preoperative evaluation of patients with peripheral vascular disease. AB - Coronary artery disease is the leading cause of death after revascularization procedures for abdominal aortic aneurysms and peripheral vascular disease. Late survival after vascular procedures is substantially reduced, largely by the high incidence of subsequent cardiac events. At the Lahey Clinic, it is not our practice to perform routine coronary angiography before elective revascularization. Thallium myocardial perfusion imaging should be performed in all patients before operation. Abnormal results on thallium exercise scanning showing multiple perfusion abnormalities or lung uptake at peak exercise identify patients who are candidates for preoperative cardiac catheterization. When severe correctable coronary artery disease is identified, these patients should be considered for coronary artery bypass surgery before vascular operation. PMID- 1913729 TI - Abdominal aortic aneurysms. AB - Modern surgical techniques permit repair of abdominal aortic aneurysms and prevent eventual rupture, with a mortality rate of only a few percent. Coronary heart disease is the chief cause of death, depriving the patient of an assumed improved life expectancy after successful operation for aneurysm. Therefore, aggressive preoperative cardiac evaluation, including coronary arteriography and perhaps more protective myocardial revascularization procedures, is indicated. PMID- 1913730 TI - Peripheral aneurysms. AB - Peripheral atherosclerotic aneurysms occur primarily in elderly men. Major complications are arterial thromboembolism with ischemia of the limb and, rarely, rupture of the aneurysm. Vascular reconstruction is associated with a low mortality, and operation is recommended. These aneurysms are often associated with arterial ectasia at other locations. The presence of peripheral atherosclerotic aneurysms always requires a search for other peripheral aneurysms, particularly in the abdominal aorta. PMID- 1913731 TI - Extracranial cerebrovascular disease. AB - The prevention, management, and prognosis of patients with transient ischemic attack or stroke caused by extracranial cerebrovascular disease depend on the underlying pathophysiologic mechanisms involved. Atherosclerotic vascular disease is the predominant pathophysiologic mechanism. Management of this entity remains controversial and should be individualized. Recent data have clearly confirmed that carotid endarterectomy is better than medical therapy. Patients with a critically tight carotid stenosis appropriate in location to their symptoms are considered for carotid endarterectomy. This procedure should be performed only in the setting of excellent neuroradiologic support and surgical expertise, however, with a cumulative complication risk of less than 3%. Intimal dissection appears to be associated with a good prognosis with or without treatment. However, patients with symptoms should receive short-term therapy with antiplatelet or anticoagulant agents to prevent distal embolization. Corticosteroids are the drugs of choice for treatment of patients with extracranial arteritis. The presence of fibromuscular dysplasia in the cerebrovascular system has not proved to be a definitive risk for stroke or transient ischemic attack. PMID- 1913732 TI - Mesenteric artery occlusive disease. AB - The age and advanced stage of atherosclerosis in this patient population require careful preoperative evaluation and attention to detail in the perioperative period in an effort to avoid complications in other organ systems resulting from diffuse occlusive disease. The keys to accurate diagnosis and successful management of patients with acute or chronic mesenteric ischemia include a detailed history, focusing on the quality and temporal relation of the symptoms; an accurate vascular assessment on physical examination, with attention directed to ruling out nonvascular causes of the symptoms; a high index of suspicion of vascular origin for otherwise unexplainable abdominal pain in the patient population at risk; an aggressive diagnostic approach with a low threshold for obtaining mesenteric angiography; CT of the abdomen to rule out occult pancreatic carcinoma; expeditious correction of metabolic and electrolyte abnormalities and optimization of cardiac function; and early surgical intervention, with directed revascularization in an effort to minimize loss of bowel from infarction. PMID- 1913733 TI - Temporal arteritis. General review with emphasis on atypical manifestations and cardiovascular complications. AB - Temporal arteritis is a common disease of the elderly. Although overall mortality does not differ between patients with temporal arteritis and the general population of similar age, temporal arteritis does cause major morbidity and death. Early diagnosis and treatment with corticosteroids can prevent these complications. PMID- 1913734 TI - Vascular skin ulcers of limbs. AB - On clinical grounds, ulcers of the leg of vascular origin can fairly easily be separated into venous and arterial origins; 85% of ulcers of the leg are caused by venous insufficiency. The ulcers occur mainly around the medial malleolus, are covered by moist granulation tissue, and are surrounded by varying degrees of stasis dermatitis and brown hemosiderin pigmentation. The limb is usually edematous and improves with elevation. In contrast, arterial ulcers of the leg develop more distally on the toes or feet, severe pain is a prominent feature, and the dry crusted ulcers usually lack granulation tissue. Elevation of the leg aggravated the pain of ischemic ulcers, whereas dependency of the limb provides some relief. Both types of ulcers heal faster with occlusive dressings that furnish a moist wound environment. Patients with ulcers caused by venous insufficiency can have coexisting peripheral atherosclerosis. Compression elastic stockings used for venous insufficiency should not be so tight that they induce necrosis of the skin in patients with occult arterial disease. PMID- 1913735 TI - Interventional radiology of the lower urinary tract and its relationship to surgical treatment. AB - Interventional radiological techniques of the lower genitourinary (GU) tract are large and varied and continue to expand because of technological advances and also because budgetary restraints are being placed on our medical society. This has stimulated continuous search for alternative ways of treating disease in a more cost-effective fashion. As a result, there has been an overall decrease in morbidity and mortality, as well as postprocedural incapacity. We review the most important and newest modalities and provide some background of the processes affecting the lower GU tract. PMID- 1913736 TI - Does the Kensey catheter keep a coaxial position inside the arterial lumen? An in vitro angioscopic study. AB - Angioscopy was used to evaluate the "self-centering" ability of three Kensey catheters (KC) with different flexibility: one 8Fr "peripheral" and two 5Fr "coronary" (I & II). Angioscopic observations were made inside arteries, 5-18 mm in diameter. There was a good correlation between flexibility and self-centering of the KC [r = 0.83, p less than 0.05]. Increasing the flow rate of rinsing solution from 18 to 60 ml/min prolonged coaxial position from 8.9 +/- 3.3 to 36 +/- 2.2 sec/min of activation [p less than 0.001]. A smaller effect on coaxial position was exerted by increasing cam speed from 5.2 +/- 0.7 to 19.2 +/- 1.6 sec/min (p less than 0.001). In conclusion, angioscopy showed that the KC has a limited ability to maintain a coaxial position inside the arterial lumen and operators cannot rely on its self-centering property. PMID- 1913737 TI - The value of SPECT-thallium scanning in screening for myocardial contusion. AB - In this prospective study of 40 patients sustaining blunt chest trauma, the value of single-photon-emission computed tomography (SPECT)-thallium scanning in the prediction of morbidity due to cardiac contusion was examined. Twelve patients developed cardiac complications--arrhythmias, ventricular conduction defects, and pericarditis. The sensitivity of SPECT-thallium scans was 55.6%, and the specificity was 32.1%, with an accuracy of 37.8%. Accuracy of the initial electrocardiogram (ECG) was 85%, with a sensitivity of 91.7% and a specificity of 82.1%. Patients with a normal ECG on admission rarely developed cardiac complications. It is concluded that SPECT-thallium is not a useful screening tool in this patient population. PMID- 1913738 TI - Bronchial arteriography and embolotherapy for hemoptysis in patients with cystic fibrosis. AB - Bronchial arteriography and embolotherapy were performed to control hemoptysis in 11 patients with advanced stages of cystic fibrosis. Two patients suffered massive, 1 moderate, and 8 mild but recurrent hemoptysis. The embolization procedures were performed with Gelfoam, Ivalon, and coils in one to four separate procedures. Altogether, 19 of 20 procedures were successful, with follow-up periods ranging from 9 months to 8 years. No serious complications were encountered except for one femoral artery pseudoaneurysm which required surgical repair. Rapid digital subtraction angiography and "roadmapping" were considered helpful in avoiding the complication of reflux embolization and expediting the procedures. Bronchial embolization is a life-saving procedure for severe hemoptysis in patients with cystic fibrosis and is considered safe enough to include the indications of moderate and mild/recurrent hemoptysis to improve the quality of life in these patients. PMID- 1913739 TI - Treatment of an esophageal perforation with enteral alimentation and transgastric drainage: case report. AB - Esophageal perforation with abscess formation has traditionally been approached surgically. A case report of percutaneous drainage of an esophageal perforation is presented. The drainage was performed in conjunction with a percutaneous gastrostomy. One catheter was placed initially in the gastric fundus for drainage and a second catheter was advanced through the gastroesophageal junction, through the perforation, and into the abscess. This management resulted in healing of the abscess cavity and sealing of the perforation. PMID- 1913740 TI - Pulmonary air embolism: case report. AB - The authors encountered a patient with an indwelling central venous catheter who presented with pulmonary edema after the catheter hub was disconnected. Pulmonary arteriography demonstrated diffuse peripheral vasoconstriction, decreased arterial-to-venous transit time, and arterial occlusions. The former two findings allowed the authors to prospectively suggest the diagnosis of pulmonary air embolism. PMID- 1913741 TI - Retrieval of a guidewire introducer by catheter-capture from the proximal inferior vena cava: technical note. AB - We report a case of a retrieval of an iatrogenically placed guidewire introducer from the proximal stump of an obstructed inferior vena cava. The retrieval of the foreign body was achieved by a technique that we have named the "catheter-capture technique."